A Molecular Electron Density Theory Study of the Reactivity of Azomethine Imine in [3+2] Cycloaddition Reactions

The electronic structure and the participation of the simplest azomethine imine (AI) in [3+2] cycloaddition (32CA) reactions have been analysed within the Molecular Electron Density Theory (MEDT) using DFT calculations at the MPWB1K/6-311G(d) level. Electron localisation function (ELF) topological analysis reveals that AI has a pseudoradical structure, while the conceptual DFT reactivity indices characterise this TAC as a moderate electrophile and a good nucleophile. The non-polar 32CA reaction of AI with ethylene takes place through a one-step mechanism with low activation energy, 5.3 kcal/mol-1. A bonding evolution theory (BET) study indicates that this reaction takes place through a non-…

Understanding the regio- and chemoselective polar [3+2] cycloaddition of the Padwa carbonyl ylides with α-methylene ketones. A DFT study

The regio- and chemoselective polar [3+2] cycloaddition (32CA) of the Padwa carbonyl ylide (CY) with α-methylene ketone (αMK) to yield the oxa-bridged spirocycloadduct has been studied using the DFT method at the B3LYP/6-31G(d) computational level. Six reactive channels associated to the stereo-, regio-, and chemoselective approach modes of the CY to the CC and CO reactive sites of the αMK have been analyzed. DFT calculations for this cycloaddition are in complete agreement with the experimental outcome, explaining the reactivity and selectivity of the formation of the [3+2] cycloadduct. Analysis of the global and local electrophilicity and nucleophilicity indices allows an explanation abou…

First synthesis of the chiral mixed O/S ligands, 1,2-sulfinyl thiols: application as chiral proton sources in enantioselective protonations of enolates

Abstract A suitable method for the preparation of the chiral mixed O/S ligands 1,2-sulfinyl thiols is described. These compounds have then been used as a chiral proton source in the enantioselective protonation of 2-methyl tetralone enolate and the results are compared with those obtained from the analogous alcohols. A theoretical model is proposed to explain the different behaviors exhibited in the protonation reaction for each of these proton sources. Configurational assignments for the new chiral thiols have been carried out by means of X-ray analysis.

ChemInform Abstract: Influence of Reactant Polarity on the Course of the Inverse-Electron-Demand Diels-Alder Reaction. A DFT Study of Regio- and Stereoselectivity, Presence of Lewis Acid Catalyst, and Inclusion of Solvent Effects in the Reaction Between N

The molecular mechanisms for the inverse-electron-demand Diels−Alder reactions between nitroethene and three substituted ethenes (propene, methyl vinyl ether, and dimethylvinylamine) to give the corresponding nitroso cycloadducts have been characterized with density functional theory methods using the B3LYP/6-31G* calculational level. On the basis of stability arguments and molecular orbital analysis relative rates, regioselectivity, and stereoselectivity, the presence of Lewis acid catalyst modeled by the BH3 system and the inclusion of solvent effects as a function of the nature of substituent in the dienophile fragment are analyzed and discussed. The ortho attack mode presents transition…

ChemInform Abstract: A New C-C Bond Formation Model Based on the Quantum Chemical Topology of Electron Density

ELF topological analyses of bonding changes in non-polar, polar and ionic organic reactions involving the participation of CC(X) double bonds make it possible to establish a unified model for C–C bond formation. This model is characterised by a C-to-C coupling of two pseudoradical centers generated at the most significant atoms of the reacting molecules. The global electron density transfer process that takes place along polar and ionic reactions favours the creation of these pseudoradical centers at the most nucleophilic/electrophilic centers of the reacting molecules, decreasing activation energies. The proposed reactivity model based on the topological analysis of the changes in electron…

Synthesis of Densely Functionalised 5-Halogen-1,3-oxazin-2-ones byHalogen-Mediated Regioselective Cyclisation of N-Cbz-ProtectedPropargylic Amines: A Combined Experimental and Theoretical Study

A very efficient synthesis of 5-halogen-1,3-oxazin-2-ones has been accomplished by the halocyclisation reaction of chiral nonracemic N-carbobenzyloxy (N-Cbz)-protected propargylic amines by using I-2, Br-2 and Cl-2 as electrophile sources. The nature of the halogen influences the reaction time and yield. However, in all cases the reaction is totally regioselective taking place through a 6-endo-dig process regardless of the nature of the halogen and of the substituents in the starting material. To rationalise the experimental results, theoretical studies at the B3LYP/6-311G* level have been performed.

A DFT study for the regioselective 1,3-dipolar cycloadditions of nitrile N-oxides toward alkynylboronates

Abstract The mechanism for the 1,3-dipolar cycloaddition of benzonitrile oxide toward ethynyl and propynylboronate has been studied by using density functional theory (DFT) at B3LYP/6-31G* level. These cycloadditions are concerted [3+2] processes. The presence of the two oxygens on the boronic ester precludes the participation of the boron atom on [3+3] processes. The two regioisomeric channels associated to the formation of the isoxazoles bearing the boronic ester unit on the 4- or 5-positions have been characterized. The B3LYP/6-31G* activation parameters are in acceptable agreement with the experiments, allowing to explain the factors controlling these regioselective cycloadditions.

Understanding the selectivity in the formation of δ-lactams vs. β-lactams in the Staudinger reactions of chloro-cyan-ketene with unsaturated imines. A DFT study

The reactions of chloro-cyan-ketene with two phenyl substituted unsaturated imines yielding β- or δ-lactams have been investigated using DFT methods at the MPWB1K/6-311G(d,p) level in diethyl ether. The reactions are initialised by the nucleophilic attack of the unsaturated imines on the ketene with formation of zwitterionic intermediates. The subsequent C–C single bond formation at the imine carbon or at the β-conjugated position enables the formation of β- or δ-lactams. Analysis of the energies involved in the two competitive channels explains the selectivity experimentally observed; in the absence of any steric hindrance, formation of δ-lactams is favoured over the formation of β-lactams…

A Molecular Electron Density Theory Study of the [3+2] Cycloaddition Reaction of Pseudo(mono)radical Azomethine Ylides with Phenyl Vinyl Sulphone

The [3+2] cycloaddition (32CA) reaction of an azomethine ylide (AY), derived from isatin and L-proline, with phenyl vinyl sulphone has been studied within Molecular Electron Density Theory (MEDT) at the ωB97X-D/6-311G(d,p) level. ELF topological analysis of AY classifies it as a pseudo(mono)radical species with two monosynaptic basins at the C1 carbon, integrating a total of 0.76 e. While vinyl sulphone has a strong electrophilic character, AY is a supernucleophile, suggesting a high polar character and low activation energy for the reaction. The nucleophilic Parr functions indicate that the pseudoradical C1 carbon is the most nucleophilic center. The 32CA reaction presents an activat…

Synthesis of (+)-podocarp-8(14)-en-13-one and methyl-(+)-13-oxo-podocarp-8(14)-en-18-oate from abietic acid

Abstract An efficient method for the preparation of (+)-podocarp-8(14)-en-13-one 6 and methyl-(+)-13-oxo-podocarp-8(14)-en-18-oate 8 from abietic acid is described.

Unveiling the Reactivity of Cyclic Azomethine Ylides in [3+2] Cycloaddition Reactions within the Molecular Electron Density Theory

An MEDT study of the mechanism and selectivities of the [3+2] cycloaddition reaction of tomentosin with benzonitrile oxide

Unveiling the regioselectivity in electrophilic aromatic substitution reactions of deactivated benzenes through molecular electron density theory

The origin of the meta regioselectivity in electrophilic aromatic substitution (EAS) reactions of deactivated benzene derivatives is herein analysed through Molecular Electron Density Theory (MEDT). To this end, the EAS reaction of benzenesulfonic acid with the nitronium NO2+ ion in H2SO4 solution has been studied at the ωB97X-D/6-311G(d,p) level. This reaction takes place through a two-step polar mechanism involving the formation of an unstable cation intermediate. The activation Gibbs free energies associated with the three competitive regioisomeric reaction paths are found in the narrow range of 15.5–18.3 kcal mol−1. By using the Eyring–Polanyi equation a relationship of 18.7 (ortho) : 8…

[3+2] Cycloaddition Reaction of C -Phenyl-N -methyl Nitrone to Acyclic-Olefin-Bearing Electron-Donating Substituent: A Molecular Electron Density Theory Study

Using theozymes for designing transition-state analogs for the intramolecular aldol reaction of δ-diketones

Two theozymes for the intramolecular aldol reaction of δ-diketones have been studied using ab initio methods. The presence of both acid/base residues favors several steps of the aldol reaction. The appropriate positioning of these residues can accelerate one of two diastereromeric reaction pathways, the catalyzed aldol reaction being highly stereoselective. Analysis of the geometrical parameters, charge distribution, and the shape of molecular electrostatic potential for the corresponding acid/base catalyzed transition structure allows us to design adequate transition-state analogs to favor a reactive channel of this intramolecular aldol reaction. © 2001 John Wiley & Sons, Inc. Int J Quant …

Applications of the Conceptual Density Functional Theory Indices to Organic Chemistry Reactivity.

Indexación: Web of Science Theoretical reactivity indices based on the conceptual Density Functional Theory (DFT) have become a powerful tool for the semiquantitative study of organic reactivity. A large number of reactivity indices have been proposed in the literature. Herein, global quantities like the electronic chemical potential μ, the electrophilicity ω and the nucleophilicity N indices, and local condensed indices like the electrophilic and nucleophilic Parr functions, as the most relevant indices for the study of organic reactivity, are discussed. http://www.mdpi.com/1420-3049/21/6/748

Toward an Understanding of the Catalytic Role of Hydrogen-Bond Donor Solvents in the Hetero-Diels−Alder Reaction between Acetone and Butadiene Derivative

A detailed theoretical investigation of the catalytic role of hydrogen-bond- (HB-) donor molecules (water, methanol, chloroform, dichloromethane, and chloromethane) in the hetero-Diels-Alder reaction between acetone and N,N-dimethyl-1-amino-3-methoxy-1,3-butadiene is presented. This work extends a previous study (Domingo, L. R.; Andres, J. J. Org. Chem. 2003, 68, 8662) in which the importance of weak HB-donor solvents to catalyze more effectively than solvents with a higher dielectric constant but no HB-donor capability was analyzed. Now, based on density functional theory (DFT) at B3LYP/6-31+G(d) level calculations, different techniques for analyzing the nature of HB interaction, namely, n…

A molecular electron density theory study of the [3 + 2] cycloaddition reaction between an azomethine imine and electron deficient ethylenes

Reactivity of the carbon-carbon double bond towards nucleophilic additions. A dft analysis

Abstract The global and local electrophilicity indexes have been used to characterize the reactivity pattern of the CC double bond towards nucleophilic addition reactions. A wide family of molecules including ketones, esters, anhydrides, nitriles and nitrocompounds containing appropriate substitution on the CC double bond have been classified within an unique scale of reactivity. The predictive capability of the theoretical model is tested against a series of benzylidenemalononitriles and substituted α-nitrostilbenes.

[3+2] Cycloaddition reaction of 1H-phosphorinium-3-olate and 1-methylphosphorinium-3-olate with methyl acrylate: A DFT study

Abstract A density functional theory study was performed on the [3+2] cycloaddition (32CA) reaction of 1H-phosphorinium-3-olate and 1-methylphosphorinium-3-olate with methyl acrylate. The thermodynamic and kinetic parameters were analysed by considering the regio- and stereoisomeric pathways in gas phase and solvents. The geometries indicate that the transition states are slightly more advanced and asynchronous in ethanol. Electron localisation function topological analysis of the bonding changes along the most favourable reaction pathway associated with the 32CA reaction of 1H-phosphorinium-3-olate with methyl acrylate indicates that the reaction takes place through a two-stage one-step me…

Understanding the regioselectivity in hetero Diels–Alder reactions. An ELF analysis of the reaction between nitrosoethylene and 1-vinylpyrrolidine

[EN] The regioselectivity in the hetero Diels-Alder reaction between nitrosoethylene 1 and 1-vinylpyrrolidine 2 has been studied by a comparative ELF bonding analysis along the IRC of the endo/ortho and endo/meta regioisomeric channels at the B3LYP/6-31G*. level. Along the most favorable endo/ortho regioisomeric channel, the C-C sigma bond is first formed by coupling of two pseudoradical centers located at the most electrophilic carbon of 1 and the most nucleophilic center of 2. Formation of these relevant pseudoradical centers, which depend on the total charge transfer process along the polar reaction, and not on the approach mode of each reagent, is well characterized by analysis of the a…

A DFT study of the mechanism of NHC catalysed annulation reactions involving α,β-unsaturated acyl azoliums and β-naphthol.

The mechanism of NHC catalysed annulation reactions involving an α,β-unsaturated acyl azolium and β-naphthol has been studied using DFT methods at the MPWB1K/6-311G(d,p) level in toluene. For the C-C bond formation step, which corresponds to the rate- and stereo-determining step of this NHC catalysed reaction, the two competitive addition modes, i.e. the 1,2- and the 1,4-additions, have been studied. In toluene, acyl azolium forms an ion pair (IP) with the counterion chloride anion. Interestingly, β-naphthol forms a hydrogen bond with the chloride anion of IP, increasing the nucleophilic character of β-naphthol and the electrophilic character of the acyl azolium moiety. For the first time, …

Unravelling the kinetics and molecular mechanism of the degenerate Cope rearrangement of bullvalene

The kinetics and molecular mechanism of the gas phase degenerate Cope rearrangement (DCR) of bullvalene have been investigated by applying quantum mechanical calculations. Highly accurate energies (CBS-QB3 and CBS-APNO) and RRKM calculations were employed to study the kinetics and ‘fall-off’ behavior. It was found that the DCR of bullvalene (C3v) occurs through a bishomoaromatic transition structure (C2v) with an energy barrier of ∼49 kJ mol−1. The calculated activation energy and enthalpy were in good agreement with the available values in the literature, but lower than those of common Cope rearrangement; this result is related to the high stabilization energy due to the interaction of the…

Influence of Reactant Polarity on the Course of the Inverse-Electron-Demand Diels−Alder Reaction. A DFT Study of Regio- and Stereoselectivity, Presence of Lewis Acid Catalyst, and Inclusion of Solvent Effects in the Reaction between Nitroethene and Substituted Ethenes

The molecular mechanisms for the inverse-electron-demand Diels−Alder reactions between nitroethene and three substituted ethenes (propene, methyl vinyl ether, and dimethylvinylamine) to give the corresponding nitroso cycloadducts have been characterized with density functional theory methods using the B3LYP/6-31G* calculational level. On the basis of stability arguments and molecular orbital analysis relative rates, regioselectivity, and stereoselectivity, the presence of Lewis acid catalyst modeled by the BH3 system and the inclusion of solvent effects as a function of the nature of substituent in the dienophile fragment are analyzed and discussed. The ortho attack mode presents transition…

A DFT study for the formation of imidazo[1,2-c]pyrimidines through an intramolecular Michael addition

The formation of imidazo[1,2-c]pyrimidines through a ring closure of 2-(2-sulfonylimino-1,2-dihydro-1-pyrimidinyl) acetamides has been studied using DFT methods. Analysis of the energy results for the cyclization step shows the demand of almost an acid catalyst, which increases the electrophilicity of the dihydropyrimidine moiety, in order to make feasible the intramolecular Michael addition. The substitution on both dihydropyrimidine and amide moieties has also an influence on the cyclization step.

Synthesis, molecular structure and stability of fused bicyclic Δ4-1,2,4-oxadiazoline Pt(II) complexes

Abstract The reaction of trans -[PtCl 2 (NCR) 2 ] (R 1  = CH 2 CO 2 Me ( 1a ), R 2  = CH 2 Cl ( 1b )) with pyrroline N -oxide − O + N CHCH 2 CH 2 C Me 2 ( 4 ), at room temperature for 15 min, furnishes via [3+2] cycloaddition the fused bicyclic Δ 4 -1,2,4-oxadiazoline Pt(II) complexes trans- [PtCl 2 { N C(R)O N C(H)CH 2 CH 2 C Me 2 } 2 ] (R 1  = CH 2 CO 2 Me ( 5a ), R 2  = CH 2 Cl ( 5b )). Compounds 5a and 5b were refluxed in CH 2 Cl 2 for 1 week to afford the derived ketoimine Pt(II) complexes trans- [PtCl 2 {N(C( O)(R)) C CH 2 CH 2 C(Me 2 ) N H} 2 ] (R 1  = CH 2 CO 2 Me ( 6a ), R 2  = CH 2 Cl ( 6b )), respectively, as a result of the N–O bond cleavage of the oxadiazoline ring in 5 . The c…

Understanding the formation of [3+2] and [2+4] cycloadducts in the Lewis acid catalysed reaction between methyl glyoxylate oxime and cyclopentadiene: a theoretical study

The formation of the formal [3+2] and [2+4] cycloadducts in the Lewis acid (LA) catalysed reaction of cyclopentadiene (Cp, 1) with methyl glyoxylate oxime (MGO, 2a) has been theoretically studied using DFT methods. Coordination of BF3 LA to the oxygen atom of MGO 2a not only increases the electrophilicity of the oxime, but also makes the corresponding tautomeric BF3:nitrone complex 8b the reactive species. The reaction is characterised by the nucleophilic attack of Cp 1 on the carbon atom of the corresponding BF3:nitrone complex 8b. The subsequent ring closure at the end of the reaction allows the formation of the [3+2] or [2+4] cycloadducts. ELF bonding analysis of selected points on the i…

Understanding the reactivity of captodative ethylenes in polar cycloaddition reactions. A theoretical study

The electrophilic/nucleophilic character of a series of captodative (CD) ethylenes involved in polar cycloaddition reactions has been studied using DFT methods at the B3LYP/6-31G(d) level of theory. The transition state structures for the electrophilic/nucleophilic interactions of two CD ethylenes toward a nucleophilically activated ethylene, 2-methylene-1,3-dioxolane, and an electrophilically activated ethylene, 1,1-dicyanoethyelene, have been studied, and their electronic structures have been characterized using both NBO and ELF methods. Analysis of the reactivity indexes of the CD ethylenes explains the reactivity of these species. While the electrophilicity of the molecules accounts for…

A DFT study of the role of Lewis acid catalysts in the mechanism of the 1,3-dipolar cycloaddition of nitrile imines towards electron-deficient acryloyl derivatives

Abstract The role of the Mg complex formation in the reaction rate and regioselectivity of the 1,3-dipolar cycloaddition (13DC) reactions of nitrile imines (NIs) towards electron-deficient methacryloylpyrazolidinones has been theoretically studied using DFT methods at the B3LYP/6-31G * level. These 13DC reactions have an asynchronous concerted mechanism with a low polar character, displaying a high C regioselectivity induced by a steric repulsion between the phenyl substituent present at the C3 carbon of the NIs and the pyrazolidinone appendage present in the methacryloyl derivative, which increases with the formation of the bulky Mg–methacryloylpyrazolidinone complex. Solvent effect has be…

ChemInform Abstract: Conjugate Addition of Organolithium Reagents to α,β-Unsaturated Carboxylic Acids.

Abstract Conjugate addition of primary, secondary, tertiary alkyl and phenyl lithium reagents to 2-alkenoic acids affords good yields of branched saturated carboxylic acids. Methyl groups at the α- and β-carbon of the 2-alkenoic acid decrease reactivity as acceptors, and foster deprotonation, respectively. The lithium enediolate resulting from the conjugate addition can react with electrophiles. PM3 calculations are in agreement with the substituent effects.

A DFT study of the domino reactions between imidazole NHC, ketenimines and DMAD or MP acetylene derivatives yielding spiro-pyrroles

Abstract The domino reactions of imidazole carbene 9, ketenimine 10 and DMAD 5 or MP 7 to yield the formal [3+2] cycloadducts 12 or 14 have been investigated using DFT methods at the B3LYP/6-31G* level. These domino reactions are initialized by the nucleophilic attack of imidazole 9 on ketenimine 10 to yield the zwitterionic intermediate 11. The second reaction is a formal [3+2] cycloaddition (32CA) reaction between the zwitterionic intermediate 11 and acetylene carboxylates DMAD 5 or MP 7 yielding spiro-pyrroles 12 and 14. These formal 32CA reactions are initialized by the nucleophilic attack of the N3 nitrogen of intermediate 11 on the most electrophilic centres of these acetylene derivat…

Understanding the participation of 3-nitropyridine in polar Diels–Alder reactions. A DFT study

The reactivity of 3-nitropyridine acting as an electrophilic dienophile in polar Diels-Alder (P-DA) reactions toward three different dienes of increased nucleophilicity has been theoretically studied using DFT methods at the MPWB1K/6-31G(d) level. It has been observed that this aromatic heterocyclic system suffers cycloaddition reactions yielding isoquinoline derivatives. The present DFT study establishes that while the P-DA reactions with isoprene and 1-methoxy-1,3-butadiene take place through a two-stage one-step mechanism, the use of the strong nucleophilic Danishefsky's diene changes the mechanism to a two-step one with formation of a zwitterionic intermediate. These P-DA reactions are …

Remarkable effect of lithium bromide in the enantioselective protonation with α-sulfinyl alcohols

Abstract The favourable effect of lithium bromide enhancing the facial enantioselectivity in the protonation of methyl tetralone enolate with α-sulfinyl alcohols is described. Theoretical calculations allow to propose a model to explain the stereochemical course of the protonation reaction.

Understanding the cooperative NHC/LA catalysis for stereoselective annulation reactions with homoenolates. A DFT study.

The role of Ti(Oi-Pr)(4) Lewis acid (LA) in the cooperative N-heterocyclic carbene (NHC)/LA catalyzed addition of enals to enones to yield cis-cyclopentenes has been investigated using DFT methods at the B3LYP/6-31G** computational level. Ti(IV) effectively catalyzes the reaction by formation of a complex with cinnamaldehyde 1, which favors the nucleophilic attack of NHC 5 on 1, and the subsequent proton abstraction to yield the extended Ti(IV)-Breslow intermediate 21. The nature of the metal involved in the LA catalyst plays a relevant role due to the more basic character of NHCs than aldehydes. Thus, strong LAs, such as Zn(OTf)(2), prevent the catalytic behavior of NHCs to form a very sta…

A DFT study of the role of the Lewis acid catalysts in the [3 + 2] cycloaddition reaction of the electrophilic nitrone isomer of methyl glyoxylate oxime with nucleophilic cyclopentene

The molecular mechanism and stereoselectivity of the BF3 Lewis acid catalyzed [3 + 2] cycloaddition (32CA) reaction between C-methoxycarbonyl nitrone and cyclopentene has been theoretically studied using DFT methods at the MPWB1K/6-31G(d) computational level. The BF3 catalyst accelerates the 32CA reaction by decreasing the activation energy leading to the formation of the trans cycloadduct as the kinetic product, in agreement with the experimental data. Inclusion of solvent effects slightly increases the activation energy and decreases the exothermic character of the 32CA reaction as a consequence of a better solvation of nitrone than the transition state and the cycloadduct. The use of the…

Experimental and theoretical study on the substitution reactions of aryl 2,4-dinitrophenyl carbonates with quinuclidines

Abstract The reactions of quinuclidines with phenyl, 4-methylphenyl, and 4-chlorophenyl 2,4-dinitrophenyl carbonates are kinetically evaluated in aqueous solution. The Bronsted-type plots (log kN vs pKa of quinuclidinium ions) are linear. The magnitude of the slopes and validated theoretical scales of electrophilicity and nucleophilicity confirm the concerted nature of these reactions.

Understanding the influence of lewis acids in the regioselectivity of the diels-alder reactions of 2-methoxy-5-methyl-1,4-benzoquinone: a dft study

The mechanisms of the Diels–Alder (DA) reactions of 2-methoxy-5-methyl-1,4-benzoquinone 1 with 2-methyl-1,3-butadiene 2, in the absence and in the presence of LA catalysts, have been studied using the DFT method at the B3LYP/6-31G(d) level of theory. The uncatalyzed DA reactions between 1 and 2 take place via synchronous concerted TSs. The large activation barrier as well as the low stereo and regioselectivity associated with the uncatalyzed process are in clear agreement with the non-polar character of the cycloaddition. Coordination of the LA catalysts, BF3 or SnCl4, to the oxygen atoms of the benzoquinone 1 produces a large acceleration of the reaction, which can be associated with the l…

Comparative theoretical study of transition structures, barrier heights, and reaction energies for the intramolecular tautomerization in acetaldehyde/vinyl alcohol and acetaldimine/vinylamine systems

The transition structures associated with the possible intramolecular tautomerization for acetaldehyde/vinyl alcohol and acetaldimine/vinylamine systems as models of keto/enol and imine/enamine interconversion processes, respectively, were characterized. The relative stabilities of the tautomers and the associated barrier heights were calculated. Ab initio analytical gradients and second derivatives at the HF level of theory and 3-21G, 6-31G, 6-31G**, 6-31++G**, and 6-311++G** basis-set, DFT (BP86/6-311++G** and BLYP/6-311++G**), and semiempirical (AM1 and PM3) procedures were used to identify the stationary points. Correlation effects were estimated using the perturbational approach at MP2…

A DFT study of the mechanism and selectivities of the [3 + 2] cycloaddition reaction between 3-(benzylideneamino)oxindole and trans -β-nitrostyrene

The mechanism and regioselectivities and stereoselectivities of the [3 + 2] cycloaddition (32CA) reaction of 3-(benzylideneamino) oxindole (AY) and trans-β-nitrostyrene have been studied using both B3LYP and ωB97XD density functional theory methods together with the standard 6-31G(d) basis set. Four reactive pathways associated with the ortho and meta regioselective channels and endo and exo stereoselective approaches modes have been explored and characterized. While the B3LYP functional fails to predict the experimental regioselectivity, the ωB97XD one succeeds to predict the experimentally observed meta regioselectivity favoring the formation of meta/endo cycloadduct as the major isomer. …

Understanding the Participation of Quadricyclane as Nucleophile in Polar [2σ + 2σ + 2π] Cycloadditions toward Electrophilic π Molecules

The formal [2sigma + 2sigma + 2pi] cycloaddition of quadricyclane, 1, with dimethyl azodicarboxylate, 2, in water has been studied using DFT methods at the B3LYP/6-31G** and MPWB1K/6-31G** levels. In the gas phase, the reaction of 1 with 2 has a two-stage mechanism with a large polar character and an activation barrier of 23.2 kcal/mol. Inclusion of water through a combined discrete-continuum model changes the mechanism to a two-step model where the first nucleophilic attack of 1 to 2 is the rate-limiting step with an activation barrier of 14.7 kcal/mol. Analysis of the electronic structure of the transition state structures points out the large zwitterionic character of these species. A DF…

A combined experimental and theoretical study of the polar [3+2] cycloaddition of electrophilically activated carbonyl ylides with aldehydes and imines

International audience; Numerous 2,5-diaryl-1,3-dioxolane-4,4-dicarbonitriles and 2,4-diphenyl-1,3-oxazolidine-5,5- dicarbonitriles have been synthesized by [3+2] cycloaddition reactions between carbonyl ylides generated from epoxides, and aldehydes or imines. In contrast to the use of aldehydes (3,4,5- trimethoxybenzaldehyde, piperonal, 1-naphthaldehyde, indole-3-carboxaldehyde, furan-2- carboxaldehyde and thiophene-2-carboxaldehyde), the reactions performed with imines (N- (phenylmethylene)methanamine, N-(1,3-benzodioxol-5-ylmethylene)propylamine, N-(1,3-benzodioxol- 5-ylmethylene)butylamine and N-(1,3-benzodioxol-5-ylmethylene)benzylamine) proceed diastereoselectively. The effect of micr…

Tautomerism in pyridazin-3(2H)-one: a theoretical study using implicit/explicit solvation models.

Abstract The tautomeric conversion of pyridazin-3(2H)-one 1 into pyridazin-3-ol 2 has been theoretically studied using density functional theory (DFT) methods at the B3LYP/6-311++G** level. Two mechanisms have been considered for this process: (i) one in which the hydrogen is directly transferred through TS12; and (ii) another one in which a double hydrogen transfer takes place via TS1122 upon formation of the corresponding dimer. The former requires a very high activation energy of 42.64 kcal/mol as a consequence of the strain associated with the formation of the four-membered TS12, while the latter requires a much lower activation energy, 14.66 kcal/mol. Implicit, explicit, and a combinat…

Ring splitting of azetidin-2-ones via radical anions

The radical anions of azetidin-2-ones, generated by UV-irradiation in the presence of triethylamine, undergo ring-splitting via N-C4 or C3-C4 bond breaking, leading to open-chain amides. This reactivity diverges from that found for the neutral excited states, which is characterised by alpha-cleavage. The preference for beta-cleavage is supported by DFT theoretical calculations on the energy barriers associated with the involved transition states. Thus, injection of one electron into the azetidin-2-one moiety constitutes a complementary activation strategy which may be exploited to produce new chemistry.

A DFT study of the Huisgen 1,3-dipolar cycloaddition between hindered thiocarbonyl ylides and tetracyanoethylene

Abstract The mechanism for the 1,3-dipolar cycloaddition between the hindered thiocarbonyl ylide 1 and tetracyanoethylene 2 has been studied at the B3LYP/6-31G ∗ level. Formation of the [3+2] cycloadduct 4 takes place through a stepwise mechanism that is initiated by the nucleophilic attack of the thiocarbonyl ylide 1 to the ethylene derivative 2 to give a zwitterionic intermediate IN . The subsequent cyclization of IN yields a seven-membered cyclic ketene imine 6 , which equilibrates with the thermodynamically more stable [3+2] cycloadduct 4 . The computed free energies are in agreement with the experimental outcomes.

On Transition Structures for Hydride Transfer Step: A Theoretical Study of the Reaction Catalyzed by Dihydrofolate Reductase Enzyme

Abstract A theoretical study is presented of the catalytic mechanism of dihydrofolate reductase (DHFR) enzyme based upon the characterization of the transition structure (TS) for the hydride transfer step. Analytical gradients at AM1 and PM3 semiempirical levels have been used to characterize the saddle point of index one (SPi-1) on global energy hypersurface for the hydride transfer in the active site of DHFR enzyme. The geometry, stereochemistry, electronic structure, and transition vector (TV) components associated to SPi-1 are qualitatively computational level independent. The TV amplitudes show primary and secondary isotope effects to be strongly coupled. The geometrical arrangement of…

Understanding the Influence of the Trifluoromethyl Group on the Selectivities of the [3+2] Cycloadditions of Thiocarbonyl S ‐methanides with α,β‐Unsaturated Ketones. A MEDT study

ChemInform Abstract: First Synthesis of the Chiral Mixed O/S Ligands, 1,2-Sulfinyl Thiols: Application as Chiral Proton Sources in Enantioselective Protonations of Enolates.

Abstract A suitable method for the preparation of the chiral mixed O/S ligands 1,2-sulfinyl thiols is described. These compounds have then been used as a chiral proton source in the enantioselective protonation of 2-methyl tetralone enolate and the results are compared with those obtained from the analogous alcohols. A theoretical model is proposed to explain the different behaviors exhibited in the protonation reaction for each of these proton sources. Configurational assignments for the new chiral thiols have been carried out by means of X-ray analysis.

Towards an intrinsic nucleofugality scale: the leaving group (lg) ability in ch(3)lg model system

Abstract For an important class of organic reactions in which a fragment of the reactants, the leaving group (LG) or nucleofuge (Z), is detached of the substrate bearing the bonding electron pair, the global electrophilicity index of the CH3LG system is proposed as a reliable descriptor of the intrinsic nucleofugality of the LG. The model is illustrated by ranking within a unique relative scale, the LG ability of 28 functional groups commonly involved in substitution and elimination reactions in organic chemistry.

A dft analysis of the participation of zwitterionic tacs in polar [3+2] cycloaddition reactions

A set of seven non-substituted tri-atom-components (TACs) participating in [3+2] cycloaddition (32CA) reactions has been studied using the reactivity indices defined within the conceptual DFT at the B3LYP/6-31G(d) level of theory. This series of TACs shows a zwitterionic structure and low reactivity towards ethylene. The general characteristic of these TACs is their high nucleophilic and a low electrophilic behaviour. Activation energies computed at the MPWB1K/6-311G(d) level in dichloromethane point to that non-substituted TACs react quickly toward dicyanoethylene showing their ability to react towards electron-deficient ethylenes. However, when the TACs are electrophilically activated by …

Understanding the Intramolecular Diels-Alder Reactions of N-Substituted N-Allyl-Furfurylamines: An MEDT Study

Understanding the stereo- and regioselectivities of the polar Diels-Alder reactions between 2-acetyl-1,4-benzoquinone and methyl substituted 1,3-butadienes: a DFT study

The polar Diels–Alder (DA) reactions of 2-acetyl-1,4-benzoquinone (acBQ) with methyl substituted 1,3-butadienes have been studied using DFT methods at the B3LYP/6-31G(d) level of theory. These reactions are characterized by a nucleophilic attack of the unsubstituted ends of the 1,3-dienes to the β conjugated position of the acBQ followed by ring-closure. The reactions present a total regioselectivity and large endo selectivity. The analysis based on the global electrophilicity of the reagents at the ground state, and the natural bond orbital (NBO) population analysis at the transition states correctly explain the polar nature of these cycloadditions. The large electrophilic character of acB…

An ELF analysis of the C–C bond formation step in the N-heterocyclic carbene-catalyzed hydroacylation of unactivated C–C double bonds

The changes in electron-density along the C–C bond-formation step in the N-heterocyclic carbene-catalyzed hydroacylation of unactivated double bonds has been studied by an electron localization function (ELF) analysis at the B3LYP/6-31G** level in order to characterize the reaction mechanism. Analysis of DFT reactivity indices and the natural bond orbital and ELF analysis at the most relevant points of the intrinsic reaction coordinate indicate that the reaction path takes place through a two-stage one-step mechanism with non-polar character. In the first stage a hydrogen atom is transferred from the hydroxyl group of Breslow intermediate 12 to the terminal olefinic carbon atom, to yield a …

WHY DIELS-ALDER REACTIONS ARE NON-CONCERTED PROCESSES

ABSTRACT Two exhaustive topological analyses using the Electron Localisation Function (ELF) along the non-polar Diels-Alder reactions of 1,3-butadiene [J. Phys. Chem. A 107 , 6014 (2003)] and cyclopentadiene [Org. Biomol. Chem. 8 , 5495, (2010)] with ethylene established that the bonding changes along these reactions are non-concerted. Herein, the ELF bonding changes along the intramolecular Diels-Alder reaction of 1-( hex-5-enyl)cyclohexa-1,3-diene is analysed. The geometrical restrictions imposed by the tether break the synchronicity in the single bond formation in this non-polar reaction. The present ELF topological analysis along this intramolecular Diels-Alder reaction supports the ear…

A molecular electron density theory study of the enhanced reactivity of aza aromatic compounds participating in Diels–Alder reactions

The enhanced reactivity of a series of four aza aromatic compounds (AACs) participating in the Diels–Alder (DA) reactions with ethylene has been studied using Molecular Electron Density Theory (MEDT). The analysis of the electronic structure of these AACs allows establishing that the substitution of the C–H unity by the isoelectronic N: unity linearly decreases the ring electron density (RED) of these compounds and concomitantly decreases their aromatic character and increases their electrophilic character. These behaviours not only decrease drastically the activation energies of these DA reactions, but also increase the reaction energies when they are compared with the very unfavourable DA…

A dft study of the regioselectivity in intramolecular diels-alder reactions with formation of a tricyclodecane skeleton

Three different intramolecular Diels-Alder (IMDA) reactions associated with the formation of fused and bridged tricyclodecane skeletons have been studied at the B3LYP/6-31G(d) computational level. While substitution on the diene and dienophile fragments modulates the polar character of the reaction, the strain effect produced by the methylene tether affects the activation energy, and its torsion controls the different regioisomeric channels of the IMDA process. Analysis of the reactivity indices recently proposed (J. Soto-Delgado et al., Org. Biomol. Chem., 2010, 8, 3678) within the conceptual density functional theory allows for the characterization of the mechanism including the charge tr…

Synthesis and characterization of molybdenum(VI)-dioxo complexes containing both coordinated thiolate and carboxylate groups. Reactions with their own free ligands

Abstract The synthesis, characterization and spectroscopic properties of a group of Mo(VI) complexes having thiocarboxylate ligands of type [MoVIO2(O2CC(S)MePh-X)2]2 have been reported (X = H, p-Me, p-Cl). The peak potential for the Mo(VI) reduction increasing according to the electron-donor ability of X (Me > H > Cl). Reaction of these Mo(VI) complexes with their own free ligands has been studied by ESR and UV-Vis spectroscopy, yielding the monomeric [MoVO(O2CC(S)MePh-X)2]− as unique complex products. The kinetic study of this oxidation reaction has also been investigated.

A molecular electron density theory (MEDT) study of the role of halogens (X2= F2, Cl2, Br2and I2) on the aza-Michael-addition reactions

Using the Molecular Electron Density Theory (MEDT), a set of uncatalyzed and X2 molecule-catalyzed (X2 = F2, Cl2, Br2, or I2) aza Michael addition reactions (aza-MARs) between pyrrolidine (PYR) and methyl acrylate (MA) have been studied in the gas phase and in dichloromethane (DCM) medium from the kinetics and molecular mechanism aspects. Analysis of the conceptual DFT reactivity indices indicates that the coordination of the X2 molecules to the oxygen of the MA's carbonyl group increases both the softness and the electrophilic character of MA, thus explaining the catalytic role of the X2 molecules. The nucleophilic attack of the nitrogen of PYR on the MA's β conjugated carbon is the rate-d…

Understanding the high reactivity of carbonyl compounds towards nucleophilic carbenoid intermediates generated from carbene isocyanides

The high reactivity of carbonyl compounds towards the carbenoid intermediate cis-IN, generated in situ by the addition of methyl isocyanide to dimethyl acetylenedicarboxylate (DMAD), has been investigated at the MPWB1K/6-311G(d,p) computational level by using Molecular Electron-Density Theory (MEDT). This multicomponent (MC) reaction is a domino process that comprises two sequential reactions: (i) the formation of a nucleophilic carbenoid intermediate trans-IN; and (ii) the nucleophilic attack of cis-IN on the carbonyl compound, resulting in the formation of the final 2-iminofuran derivative. The present MEDT study establishes that the high nucleophilic character and the electronic structur…

Enhancing reactivity of carbonyl compounds via hydrogen-bond formation. A DFT study of the hetero-Diels-Alder reaction between butadiene derivative and acetone in chloroform.

To examine how hydrogen-bond (HB) formation involving chloroform solvent molecules influences the chemical reactivity of ketones, the hetero-Diels-Alder reaction of N,N-dimethyl-1-amino-3-methoxy-1,3-butadiene and acetone has been studied by using density functional theory (DFT) at the B3LYP/6-31G level. The effects of the chloroform on the activation energies have been modeled by means of discrete-continuum models. In the gas phase, the formation of specific HB between acetone and one and two chloroform molecules decreases the activation barriers from 19.3 to 13.6 and 8.5 kcal/mol, respectively. Inclusion of solvent effects by means of combined discrete and polarizable continuum models yie…

Unveiling the Substituent Effects in the Stereochemistry of [3+2] Cycloaddition Reactions of Aryl‐ and Alkyldiazomethylphosphonates with Norbornadiene within a MEDT Perspective

Understanding local electrophilicity/nucleophilicity activation through a single reactivity difference index.

A local reactivity difference index R(k) is shown to be able to predict the local electrophilic and/or nucleophilic activation within an organic molecule. Together with the electrophilic and/or nucleophilic behavior of the center k given by the sign, the magnitude of the R(k) index accounts for the extent of the electronic activation, a behavior that allows for the use of the R(k) index as a measure of the molecular reactivity especially in polar processes.

A DFT Study of Inter- and Intramolecular Aryne Ene Reactions

The molecular mechanisms of inter- and intramolecular aryne-ene reactions have been theoretically studied by DFT methods at the MPWB1K/6-311G(d,p) level. These reactions proceed through a one-step mechanism via nearly asynchronous transition states (TSs), in which the C–C single bond formation is slightly more advanced than the hydrogen transfer process. These ene reactions show very low activation enthalpies (<1 kcal/mol) and are strongly exothermic by more than 73 kcal/mol. An electron localisation function (ELF) topological analysis of the changes of electron density during these ene reactions indicates that the bonding changes are nonconcerted. ELF topological analysis of the electron d…

A Molecular Electron Density Theory Study of the Chemoselectivity, Regioselectivity, and Diastereofacial Selectivity in the Synthesis of an Anticancer Spiroisoxazoline derived from α-Santonin

The [3 + 2] cycloaddition (32CA) reaction of an &alpha

CONVERSION OF RESIN ACIDS INTO STEROIDAL COMPOUNDS. A REVIEW

(1991). CONVERSION OF RESIN ACIDS INTO STEROIDAL COMPOUNDS. A REVIEW. Organic Preparations and Procedures International: Vol. 23, No. 3, pp. 321-356.

[MoO2(SCPh2CO2)2]2− and [MoO(SCPh2CO2)2]− anion complexes. A theoretical structure characterization

Abstract Geometry optimization of [MoO 2 (SCH 2 CO 2 ) 2 ] 2− and [MoO(SCH 2 CO 2 ) 2 ] − systems as models of [MoO 2 (SCPh 2 CO 2 ) 2 ] 2− and [MoO(SCPh 2 CO 2 ) 2 ] − anion complexes have been carried out at STO-3G, 3-21G, LANL1MB and LANL2DZ basis set levels. A comparison of the theoretical results and X-ray experimental data has been performed. STO-3G minimal basis set produces the best geometrical agreement, in particular the distances and orientations of the different ligands linked to molybdenum transition metal. A large structural overlap with STO-3G optimized geometry and X-ray data has been found for the [MoO 2 (SCPh 2 CO 2 ) 2 ] 2− and [MoO(SCPh 2 CO 2 ) 2 ] − anion complexes.

A DFT study of [3 + 2] cycloaddition reactions of an azomethine imine with N-vinyl pyrrole and N-vinyl tetrahydroindole

The mechanism and selectivities of the [3+2] cycloaddition (32CA) reactions of azomethine imine (AI) 8 with two N-vinyl five-membered heterocycles (NVFH), 9a and 9b, have been theoretically studied using DFT methods at the MPWB1K/6-31G(d) computational level. The possible ortho/meta regio- and endo/exo stereoselective channels were explored and characterised. The low polar character of these 32CA reactions, which is the consequence of the high nucleophilic character of both reagents, as well as the non-effective reactivity of these NVFH as nucleophiles, accounts for the high calculated activation energies, 16.1 (9a) and 16.8 (9b) kcalmol-1 in chlorobenzene. Analysis of the relative electron…

Formation of Pyrazol-1,3,4-Thiadiazoles through 1,3-Dipolar Cycloadditions of 3-Thioxo-[1,2,4]-Triazepin-5-one with Nitrilimines: An Experimental and Computational study

In this work the results of experimental and computational study of the title compounds and some ancillary compounds are reported. Two bicyclic pyrazol-1,3,4-thiadiazole derivatives were synthesized by reaction between 6-dimethylaminomethylene-3-thioxo-[1,2,4]- triazepin-5-one 1 and several nitrilimines 2a-f to give corresponding spirocycloadducts 3a-f, which undergo a rapid rearrangement leading to the new bicyclic compounds, 4a-f and 5a-f. These obtained bicyclic products were characterized by 1H and 13C NMR spectroscopy and finally by X-ray crystallography. Theoretical calculations have been carried out using DFT methods to rationalize the formation of the two new bicyclic compounds. Two…

Toward an Understanding of the Mechanisms of the Intramolecular [5 + 2] Cycloaddition Reaction of γ-Pyrones Bearing Tethered Alkenes. A Theoretical Study

The molecular mechanism for the intramolecular [5 + 2] cycloaddition reaction of β-silyloxy-γ-pyrones bearing tethered alkenes has been characterized using ab initio methods. A comparative study for this sort of cycloaddition carried out at different computational levels points out that the B3LYP/6-31G* calculations give similar barriers to those obtained with the MP3/6-31G* level. Analysis of the energetic results shows that the reaction takes place along a stepwise process:  first, the migration of the neighboring silyl group to the carbonyl group of the γ-pyrone takes place to give a weak oxidopyrylium ylide intermediate, which by a subsequent concerted intramolecular [5 + 2] cycloadditi…

A new C–C bond formation model based on the quantum chemical topology of electron density

ELF topological analyses of bonding changes in non-polar, polar and ionic organic reactions involving the participation of CC(X) double bonds make it possible to establish a unified model for C–C bond formation. This model is characterised by a C-to-C coupling of two pseudoradical centers generated at the most significant atoms of the reacting molecules. The global electron density transfer process that takes place along polar and ionic reactions favours the creation of these pseudoradical centers at the most nucleophilic/electrophilic centers of the reacting molecules, decreasing activation energies. The proposed reactivity model based on the topological analysis of the changes in electron…

Chapter 9 The electrophilicity index in organic chemistry

Abstract We review in this chapter the applications of theoretical scales of global and local electrophilicity to rationalize the reactivity and selectivity for a significant number of reactions in organic chemistry. The model is based on the global electrophilicity index, formerly introduced by Maynard et al. and further formalized by Parr et al. The global electrophilicity index categorizes, within a unique absolute scale, the propensity of electron acceptors to acquire additional electronic charge from the environment. The local extension of this index provides useful information about the active sites of electrophiles, thereby allowing the characterization of the intramolecular selectiv…

A new model for C–C bond formation processes derived from the Molecular Electron Density Theory in the study of the mechanism of [3+2] cycloaddition reactions of carbenoid nitrile ylides with electron-deficient ethylenes

Abstract The [3+2] cycloaddition (32CA) reactions of the nitrile ylide (NY) with ethylene and with dicyanoethylene (DCE) have been studied using the Molecular Electron Density Theory through DFT calculations at the MPWB1K/6-31G(d) level. The analysis of the electronic structure of NY indicates that it presents a carbenoid structure with an sp 2 lone pair at the carbon atom. While the 32CA reaction with ethylene presents a low activation energy, 6.1 kcal mol −1 , the transition state structure associated with the 32CA reaction of NY with DCE is located 7.5 kcal mol −1 below the reagents, the reaction being completely regioselective. The topological analysis of the Electron Localisation Funct…

A DFT study of the asymmetric (S)-5-(pyrrolidin-2-yl)-1H-tetrazole catalyzed Michael addition of carbonyl compounds to nitroalkenes

Abstract The role of the ( S )-5-(pyrrolidin-2-yl)-1 H -tetrazole in the asymmetric organocatalyzed Michael addition of carbonyl compounds to nitroalkenes has been studied using DFT methods at the B3LYP/6-31G ∗∗ computational level. For the C–C bond-formation step, several reactive channels have been analyzed. The B3LYP/6-31G ∗∗ results, which are in reasonable agreement with the experiments, allow us to explain the stereoselectivity and the increase of the reactivity achieved by an intramolecular HB between the acid hydrogen of the tetrazole moiety and one oxygen atom of the nitroalkene.

A Molecular Electron Density Theory Study of the Role of the Copper Metalation of Azomethine Ylides in [3 + 2] Cycloaddition Reactions.

The copper metalation of azomethine ylides (AYs) in [3 + 2] cycloaddition (32CA) reactions with electron-deficient ethylenes has been studied within the Molecular Electron Density Theory (MEDT) at the MPWB1K/6-311G(d,p) level, in order to shed light on the electronic effect of the metalation in the course of the reaction. Analysis of the Conceptual Density Functional Theory reactivity indices indicates that the metalation of AYs markedly enhances the nucleophilicity of these species given the anionic character of the AY framework. These 32CA reactions take place through stepwise mechanisms characterized by the formation of a molecular complex. Both nonmetalated and metalated 32CA reactions …

Diastereomeric Differentiation in the Quenching of Excited States by Hydrogen Donors

A molecular electron density theory study of the chemo- and regioselective [3 + 2] cycloaddition reactions between trifluoroacetonitrile N-oxide and thioketones

Abstract The [3 + 2] cycloaddition (32CA) reaction between trifluoroacetonitrile N-oxide (NO 7) and 2,2,4,4-tetramethyl-3-thioxocyclobutan-1-one (THK 12) as well as the self-dimerization of NO 7 as a competitive pathway were studied within the Molecular Electron Density Theory (MEDT) using several DFT functionals together with def2-TZVP basis set. Taking CCSD(T)/TZVP activation energies as reference, among the employed functionals, just the B2PLYP-D3(BJ) one is able to portray complete predominance of 32CA reaction over self-dimerization process in excellent agreement with the experimental outcomes. Analysis of the global reactivity indices permits to characterize NO 7 and THK 12 as a stron…

Effect of electron-withdrawing substituents on the electrophilicity of carbonyl carbons

Indexación: Scopus The substituent effects on the carbonyl carbon atom for a series of twelve substituted phenyl acetates have been rationalized using a global electrophilicity index. This index is linearly correlated with the experimental reaction rate coefficients. We found that, in contrast to the proposed interpretation based on experimental 13C NMR chemical shifts and ground state destabilization calculations, the electrophilicity of carbonyl compounds increases due to the effect promoted by electron-withdrawing groups in these systems. https://www.sciencedirect.com/science/article/pii/S0040402004018046?via%3Dihub

Complementarity of reaction force and electron localization function analyses of asynchronicity in bond formation in diels-alder reactions

We have computationally compared three Diels-Alder cycloadditions involving cyclopentadiene and substituted ethylenes; one of the reactions is synchronous, while the others are slightly or highly asynchronous. Synchronicity and weak asynchronicity are characterized by the reaction force constant κ(ξ) having just a single minimum in the transition region along the intrinsic reaction coordinate ξ, while for high asynchronicity κ(ξ) has a negative maximum with minima on both sides. The electron localization function (ELF) shows that the features of κ(ξ) can be directly related to the formation of the new C-C bonds between the diene and the dienophile. There is thus a striking complementarity b…

Theoretical study on the molecular mechanism of the [5 + 2] vs. [4 + 2] cyclization mediated by Lewis acid in the quinone system

[EN] The thermal and Lewis acid (LA) catalyzed cyclizations of quinone 1 involved in the synthesis of Colombiasin A and Elipsaterosin B have been theoretically studied using DFT methods at the B3LYP/6-311G(d,p) computational level. B3LYP calculations suggest that the formal endo [4 + 2] cycloadduct allowing the synthesis of Colombiasin A is preferentially formed under thermal conditions, while in the presence of the BF3 LA catalyst the formal [5 + 2] cycloadduct is seen, allowing the synthesis of Elipsaterosin B. The BF3 LA catalyst not only accelerates the nucleophilic attack on the C2 carbon of the quinone framework through a more polar C-C bond formation, but also provokes a different el…

Unveiling the Chemistry of Higher-Order Cycloaddition Reactions within the Molecular Electron Density Theory

The higher-order cycloaddition (HOCA) reaction of tropone with cyclopentadiene (Cp) has been studied within the Molecular Electron Density Theory. The Electron Localization Function (ELF) analysis of the electronic structure of tropone and Cp characterizes the structural behaviors of the two conjugated unsaturated systems, while the conceptual DFT reactivity indices classify tropone as a strong electrophile and Cp as a strong nucleophile participating in polar cycloaddition reactions of reverse electron density flux. Eight competitive reaction paths have been characterized for this cycloaddition reaction. The most favorable one allowing the formation of the formal out [6 + 4] cycloadduct ha…

Scandium-catalyzed preparation of cytotoxic 3-functionalized quinolin-2-ones: Regioselective ring enlargement of isatins or imino isatins

Trimethylsilyldiazomethane in the presence of catalytic amounts of Sc(OTf) 3 smoothly promotes the ring expansion of isatins or imino isatins to efficiently afford 3-functionalized quinolin-2-ones through controlled ring enlargement. Whereas the ring-expansion reaction of azetidine-2,3-diones led to the adduct resulting from migration of the carbonyl group, the ring-expansion reaction of oxindole derivatives gave the adduct resulting from migration of the aryl group. To rationalize the experimental observations, theoretical studies have been performed. Moreover, the biological activity of some of the synthesized heterocycles has been evaluated in four cancer cell lines. © 2012 Wiley-VCH Ver…

Unravelling the strain-promoted [3+2] cycloaddition reactions of phenyl azide with cycloalkynes from the molecular electron density theory perspective

The strain-promoted [3+2] cycloaddition (SP-32CA) reactions of phenyl azide with a series of five strained cycloalkynes C5–C9 have been studied within molecular electron density theory (MEDT) at the MPWB1K/6-311G(d,p) computational level. These zwitterionic type SP-32CA reactions take place through a one-step mechanism, with activation enthalpies in acetonitrile between −4.2 and 19.9 kcal mol−1. An excellent linear correlation between the decrease in activation enthalpies and the ring size of this series of cycloalkynes can be established. The present study shows that the highly strained cycloalkynes C5 and C6 experience a different chemical reactivity than less strained cycloalkynes C7–C9,…

Theoretical study of 1,3-dipolar cycloaddition reactions with inverse electron demand - A DFT study of the lewis acid catalyst and solvent effects in the reaction of nitrones with vinyl ethers

The molecular mechanism for the inverse electron demand 1,3-dipolar cycloaddition of nitrones with vinyl ethers has been characterized using density functional theory methods with the B3LYP functional and the 6−31G* basis set. Relative rates, regioselectivity, endo/exo stereoselectivity, Lewis acid catalyst and solvent effects are analyzed and discussed. Four reactive channels associated with the formation of two pairs of diasteromeric regioisomers have been characterized. Analysis of the geometries of the corresponding transition structures shows that the reaction in the gas phase takes place by an asynchronous concerted mechanism. These 1,3-dipolar cycloadditions present a large ortho reg…

Understanding the Mechanism of the Intramolecular Stetter Reaction. A DFT Study

The mechanism of the N-heterocyclic carbene (NHC)-catalyzed intramolecular Stetter reaction of salicylaldehyde 1 to yield chromanone 3 has been theoretically studied at the B3LYP/6-31G** level. This NHC-catalyzed reaction takes place through six elementary steps, which involve: (i) formation of the Breslow intermediate IN2; (ii) an intramolecular Michael-Type addition in IN2 to form the new C-C s bond; and (iii) extrusion of the NHC catalyst from the Michael adduct to yield chromanone 3. Analysis of the relative free energies in toluene indicates that while formation of Breslow intermediate IN2 involves the rate-determining step of the catalytic process, the intramolecular Michael-type addi…

Potential energy surface for the decomposition of mandelic acid

Abstract The decomposition of mandelic acid has been studied by ab initio calculations at the MP2/6-31G ∗∗ level. Three competitive reaction pathways have been characterized, two are stepwise processes with the formation of an α-lactone intermediate, achieved by the nucleophilic attack of either the carbonylic oxygen atom (mechanism A) or the hydroxylic oxygen atom (mechanism B) of the carboxyl group, followed by a ring opening; the third pathway (mechanism C) is a one-step process. The calculated rate coefficient agrees with experimental data. The decomposition is energetically favourable along mechanism A.

Divulging the various chemical reactivity of trifluoromethyl-4-vinyl-benzene as well as methyl-4-vinyl-benzene in [3+2] cycloaddition reactions.

Abstract In the present paper, an investigation about the [3 + 2]cycloaddition (32 C A) reactions of benzonitrile oxide with 1-trifluoromethyl-4-vinyl-benzene, and with 1-methyl-4-vinyl-benzene, using the Molecular Electron Density Theory (MEDT) through DFT/B3LYP/6–311++G (d,p), is performed. A deep mechanistic study beside an accurate electronic description of different stationary points along the IRC paths of the two 32 C A reactions have performed by examining the two competitive regioisomericortho/metareaction pathways, and providing the mechanism associated with them. The presence of the CF3 group reduces the activation energy, which makes it possible to increase the experimental yield…

Xanthone-photosensitized detoxification of the veterinary anthelmintic fenbendazole

Fenbendazole (1) is a common veterinary anthelmintic, toxic to water living microorganisms. Fluorescence quantum yields of 1 were found to be 0.11 in acetonitrile, 0.068 in methanol, 0.034 in cyclohexane, and 0.013 in water. The singlet excited state energy was ca. 96 kcal mol(-1) in all solvents. The phosphorescence spectrum of 1 in ethanol at 77 K displayed a maximum at 450 nm, leading to a triplet energy of 75 kcal mol(-1). Experimental excited state energies agree well with the results of OFT calculations at the time-dependent B3LYP/6-311+G(d,p)//B3LYP/6-31G(d) level. Laser flash photolysis (LFP) of 1 at 266 nm led to transients absorbing in the 300-700 nm range, ascribed to radical cat…

Unveiling the Different Reactivity of Bent and Linear Three-Atom-Components Participating in [3 + 2] Cycloaddition Reactions

The reactivity of a series of pairs of bent and linear three-atom-component (B-TACs and L-TACs) participating in [3 + 2] cycloaddition (32CA) reactions towards ethylene and electrophilic dicyanoethylene (DCE) have been studied within the Molecular Electron Density Theory. While the pseudodiradical structure of B-TACs changes to that of pseudoradical or carbenoid L-TACs upon dehydrogenation, zwitterionic B-TACs remain unchanged. Conceptual Density Functional Theory (CDFT) indices characterize five of the nine TACs as strong nucleophiles participating in polar reactions towards electrophilic ethylenes. The activation energies of the 32CA reactions with electrophilic DCE range from 0.5 to 22.0…

Toward an understanding of the 1,3-dipolar cycloaddition between diphenylnitrone and a maleimide:bisamide complex. A DFT analysis of the reactivity of symmetrically substituted dipolarophiles

Abstract The 1,3-dipolar cycloaddition between diphenylnitrone and a maleimide:bisamide complex has been studied using density functional theory (DFT) methods at the B3LYP/6-31G∗ level. The molecular recognition of the bisamide receptor to maleimide favors the formation of the complex through three hydrogen bonds. However, they are not able to produce an efficient acceleration of the cycloaddition because the symmetric substitution of the dipolarophile sites. This poor capability is discussed in base of the transition state structures and the analysis of the reactivity indexes of the reagents.

The 1,3-dipolar cycloaddition of 1H-pyridinium-3-olate and 1-methylpyridinium-3-olate with methyl acrylate: a density functional theory study

The 1,3-dipolar cycloaddition reaction of 1-substituted pyridinium 3-olates with methyl acrylate is studied using density functional theory (DFT) method at the B3LYP/6-31G(d) level. The molecular mechanisms of the possible stereo- and regio-chemical pathways are characterized and explored. Solvent effects are also evaluated by the polarizable continuum model (PCM). Analysis of the results shows that there are relevant differences in the reaction pathways between the gas phase and with solvent. Only results in solvent phase are in accord with literature experimental results where 6-substituted 8-azabicyclo[3.2.1]oct-3-en-2-ones are formed preferentially. These polar cycloaddition reactions t…

Experimental and Theoretical MEDT Study of the Thermal [3+2] Cycloaddition Reactions of Aryl Azides with Alkyne Derivatives

A theoretical study on the regioselectivity of 1,3-dipolar cycloadditions using dft-based reactivity indexes

The regioselectivity for a series of four 1,3-dipolar cycloaddition reactions has been studied using global and local reactivity indexes. The results of the theoretical analysis suggest that for asynchronous cycloadditions associated to polar processes, the regioselectivity is consistently explained by the most favorable two-center interactions between the highest nucleophilic and electrophilic sites of the reagents.

Unveiling the high reactivity of cyclohexynes in [3 + 2] cycloaddition reactions through the molecular electron density theory

[3 + 2] cycloaddition (32CA) reactions of cyclohexyne, a cyclic strained acetylene, with methyl azide and methoxycarbonyl diazomethane have been studied within the Molecular Electron Density Theory (MEDT) at the MPWB1K/6-311G(d) computational level. These 32CA reactions, which take place through a one-step mechanism involving highly asynchronous transition state structures, proceed with relatively low activation enthalpies of 6.0 and 4.3 kcal mol-1, respectively, both reactions being strongly exothermic. The reactions are initiated by the creation of a pseudoradical center at one of the two acetylenic carbons of cyclohexyne with a very low energy cost, 1.0 kcal mol-1, which promotes the eas…

Experimental and theoretical study of the [3+2] cycloaddition of carbonyl ylides with alkynes

[EN] The [3 + 2] cycloaddition reaction between carbonyl ylides generated from epoxides and alkynes (phenylacetylene, methyl propiolate, methyl but-2-ynoate and methyl 3-phenylpropiolate) to give substituted 2,5-dihydrofurans was investigated. The effect of indium(III) chloride on the outcome of the reaction was studied in the case of phenylacetylene and methyl propiolate. The thermal reaction between the carbonyl ylide coming from 2,2-dicyano-3-phenyloxirane and both methyl propiolate and methyl but-2-ynoate was theoretically investigated using DFT methods in order to explain the reactivity and regioselectivity observed.

Unveiling the Ionic Diels-Alder Reactions within the Molecular Electron Density Theory

The ionic Diels–Alder (I-DA) reactions of a series of six iminium cations with cyclopentadiene have been studied within the Molecular Electron Density Theory (MEDT). The superelectrophilic character of iminium cations, ω &gt

ChemInform Abstract: New Highly Asymmetric Henry Reaction Catalyzed by CuIIand a C1-Symmetric Aminopyridine Ligand, and Its Application to the Synthesis of Miconazole.

A new catalytic asymmetric Henry reaction has been developed that uses a C(1)-symmetric chiral aminopyridine ligand derived from camphor and picolylamine. A variety of aromatic, heteroaromatic, aliphatic, and unsaturated aldehydes react with nitromethane and other nitroalkanes in the presence of DIPEA (1.0 equiv), Cu(OAc)(2)*H(2)O (5 mol %), and an aminopyridine ligand (5 mol %) to give the expected products in high yields (up to 99 %), moderate-to-good diastereoselectivites (up to 82:18), and excellent enantioselectivities (up to 98 %). The reaction is air-tolerant and has been used in the synthesis of the antifungal agent miconazole.

A DFT Study of the Molecular Mechanisms of the Diels−Alder Reaction between Cyclopentadiene and 3-Phenyl-1-(2-pyridyl)-2-propen-1-one − Role of the Zn2+ Lewis Acid Catalyst and Water Solvent

The molecular mechanism of the Diels−Alder reaction between cyclopentadiene (1) and 3-phenyl-1-(2-pyridyl)-2-propen-1-one (2) in the absence and in the presence of a Zn2+ Lewis acid catalyst has been studied by quantum mechanical calculations at the B3LYP/6-31G* level of theory. A continuum model was selected to represent the effects of the water as solvent. For the uncatalyzed process, two channels, endo and exo, were characterized, and the mechanism corresponded to an asynchronous concerted reaction associated with a [4+2] process. The presence of a Lewis acid catalyst changed the mechanism drastically, the reaction taking place by a polar stepwise mechanism. In the first step, a C−C sigm…

Influence of conformational factors on acid-catalyzed cyclizations of germacranolides: Molecular structure of the cyclization products of gallicin and 8α-hydroxygallicin (shonachalin a)

Acid-catalyzed cyclization of the natural germacranolide gallicin (8) yielded, among other products, the 1,4-epoxyeudes-manolide 9, which has a trans-fused decaline system. Under the same conditions the closely related germacranolide shonachalin A (8α-hydroxygallicin) (3) cyclized to the eudesmanolide 4 with a cis fused decaline system. The structures of these cyclization products were secured by means of chemical correlations and X-ray diffraction analyses.

A DFT study of the polar Diels–Alder reaction between 4-aza-6-nitrobenzofuroxan and cyclopentadiene

Abstract The polar Diels–Alder reaction between 4-aza-6-nitrobenzofuroxan (ANBF) and cyclopentadiene has been studied using DFT procedures at the B3LYP/6-31G* level. Only one highly asynchronous transition state structure associated to the formation of the [4+2] adduct 13 is found. A further [3,3] sigmatropic shift on the [4+2] cycloadduct 13 allows its conversion into the thermodynamically more stable [2+4] cycloadduct 14 . The analysis of the global and local electrophilicities of the reagents correctly explain the behaviour of ANBF as a strong electrophile in polar cycloadditions.

A mechanistic study of the participation of azomethine ylides and carbonyl ylides in [3+2] cycloaddition reactions

The participation of azomethine ylides (AYs) and carbonyl ylides (CYs) in [3+2] cycloaddition (32CA) reactions has been analysed at the DFT B3LYP/6-31G(d) level. The asymmetric substitution breaks the pseudodiradical character of the simplest three-atom-components (TACs), modifying their electrophilic and nucleophilic behaviours. These TACs react quickly towards electrophilic nitroethylene. However, while the reaction with AY takes place via a zw-type mechanism, the reaction with CY appears to take place via a pr-type mechanism. A different behaviour is found in the reactivity towards the nucleophilic methyl vinyl ether. While AY presents a high activation energy, CY presents a high reactiv…

Ionic liquids and microwave irradiation as synergistic combination for polar Diels–Alder reactions using properly substituted heterocycles as dienophiles: A DFT study related

For the DA reactions between nitropyrrole derivatives and isoprene, the combination of microwave irradiation and protic ionic liquid, has a notable synergistic effect. DFT calculations suggest that a supplementary energy ranking in the IR region of 1700-1400 cm-1 can favour the structural changes in the reactants to reach the TS. Fil: Mancini, Pedro Maximo Emilio. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Departamento de Química; Argentina Fil: Ormachea, Carla. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa F…

Design, Synthesis, Chemical and Biochemical Insights Into Novel Hybrid Spirooxindole-Based p53-MDM2 Inhibitors With Potential Bcl2 Signaling Attenuation

The tumor resistance to p53 activators posed a clinical challenge. Combination studies disclosed that concomitant administration of Bcl2 inhibitors can sensitize the tumor cells and induce apoptosis. In this study, we utilized a rapid synthetic route to synthesize two novel hybrid spirooxindole-based p53-MDM2 inhibitors endowed with Bcl2 signaling attenuation. The adducts mimic the thematic features of the chemically stable potent spiro [3H-indole-3,2′-pyrrolidin]-2(1H)-ones p53-MDM2 inhibitors, while installing a pyrrole ring via a carbonyl spacer inspired by the natural marine or synthetic products that efficiently inhibit Bcl2 family functions. A chemical insight into the two synthesized…

Understanding the mechanism of the Povarov reaction. A DFT study

The molecular mechanism of the Povarov reaction in acetonitrile has been studied at the MPWB1K/6-311G** level of theory. This reaction follows a domino process that comprises two sequential reactions: (i) a Lewis acid catalysed aza-Diels–Alder (A-DA) reaction between a N-aryl imine and a nucleophilic ethylene yielding a formal [4 + 2] cycloadduct; (ii) a stepwise 1,3-hydrogen shift at this intermediate affording the final tetrahydroquinoline. At this computational level, the Lewis acid catalysed A-DA reaction presents a two-step mechanism as a consequence of the large stabilisation of the corresponding zwitterionic intermediate. Our study allows establishing that the N-aryl substituent has …

Exploring two-state reaction pathways in the photodimerization of cyclohexadiene.

The ground- (S0) and lowest triplet-state (T1) pathways associated with dimerization of cyclohexadiene to give [2+2] and [4+2] cycloadducts have been theoretically studied at the UBLYP and UB3LYP levels of theory with the 6-31G* basis set. The DFT energies were validated by CCSD(T) single-point energy calculations. These cycloaddition reactions follow stepwise mechanisms with formation of bis-allylic biradical (BB) intermediates. In the S0 ground state, the interaction between two cyclohexadiene molecules with formation of BB intermediate IN(S0) has a large activation enthalpy of 32.0 kcal mol(-1). On the other hand, C-C bond-formation in the lowest triplet state (T1) leading to BB intermed…

Global and local reactivity indices for electrophilic/nucleophilic free radicals

A set of five DFT reactivity indices, namely, the global electrophilicity ω° and nucleophilicity N° indices, the radical Parr function P°k, and the local electrophilicity ω°k and nucleophilicity N°k indices, for the study of free radicals (FRs) are proposed. Global indices have been tested for a series of 32 FRs having electrophilic and/or nucleophilic activations. As expected, no correlation between the proposed global electrophilicity ω° and global nucleophilicity N° has been found. Analysis of the local electrophilicity ω°k and nucleophilicity N°k indices for FRs, together with analysis of the local electrophilicity ωk and nucleophilicity Nk indices for alkenes, allows for an explanation…

Understanding the local reactivity in polar organic reactions through electrophilic and nucleophilic Parr functions

[EN] Building upon our recent studies devoted to the bonding changes in polar reactions [RSC Advances, 2012, 2, 1334 and Org. Biomol. Chem., 2012, 10, 3841], we propose herein two new electrophilic, P-k(+), and nucleophilic, P-k(-), Parr functions based on the spin density distribution at the radical anion and at the radical cation of a neutral molecule. These local functions allow for the characterisation of the most electrophilic and nucleophilic centres of molecules, and for the establishment of the regio- and chemoselectivity in polar reactions. The proposed Parr functions are compared with both, the Parr-Yang Fukui functions [J. Am. Chem. Soc. 1984, 106, 4049] based on frontier molecul…

On the nature of parr functions to predict the most reactive sites along organic polar reactions

Abstract Very recently, local electrophilic and nucleophilic “Parr functions” were empirically introduced (L.R. Domingo, P. Perez, J.A. Saez RSC Adv. 3 (2013) 1486) in order to properly characterize the most reactive sites along polar chemical reactions. This Letter reports a theoretical advance to the new methodology by identifying these quantities with key Fukui descriptors of the spin-polarized density functional theory . Given such framework properly incorporates the treatment of both charge-transfer and spin-polarization, this finding provides a significant insight and substantial step forward within the field of a chemical reactivity theory based on the conceptual framework of density…

A bonding evolution theory study of the mechanism of [3+2] cycloaddition reactions of nitrones with electron-deficient ethylenes

The mechanism of zw-type [3+2] cycloaddition (32CA) reactions of nitrones with electron-deficient (ED) ethylenes has been studied using density functional theory (DFT) methods at the MPWB1K/6-31G(d) level of theory. An exploration of the potential energy surfaces associated with the four competitive reactive channels of the 32CA reaction between C-phenyl-N-methyl nitrone and acrolein indicates that the cycloaddition reaction takes place through a one-step mechanism. This cycloaddition reaction presents a moderate meta regioselectivity and a complete endo stereoselectivity, which is diminished in dichloromethane. Analysis of the DFT reactivity indices of the reagents allows an explanation of…

Understanding the domino reaction between 1-diazopropan-2-one and 1,1-dinitroethylene. A molecular electron density theory study of the [3 + 2] cycloaddition reactions of diazoalkanes with electron-deficient ethylenes

The reaction between 1-diazopropan-2-one and 1,1-dinitroethylene has been studied using the Molecular Electron Density Theory (MEDT) at the B3LYP/6-31G(d,p) computational level. This reaction comprises two domino processes initialised by a common [3 + 2] cycloaddition (32CA) reaction yielding a 1-pyrazoline, which participates in two competitive reaction channels. Along channel I, 1-pyrazoline firstly tautomerises to a 2-pyrazoline, which by a proton abstraction and spontaneous loss of nitrite anion yields the final pyrazole, while along channel II, the thermal extrusion of the nitrogen molecule in 1-pyrazoline gives a very reactive diradical intermediate which quickly yields the final gem-…

Unveiling the Intramolecular Ionic Diels–Alder Reactions within Molecular Electron Density Theory

The intramolecular ionic Diels–Alder (IIDA) reactions of two dieniminiums were studied within the Molecular Electron Density Theory (MEDT) at the ωB97XD/6-311G(d,p) computational level. Topological analysis of the electron localization function (ELF) of dieniminiums showed that their electronic structures can been seen as the sum of those of butadiene and ethaniminium. The superelectrophilic character of dieniminiums accounts for the high intramolecular global electron density transfer taking place from the diene framework to the iminium one at the transition state structures (TSs) of these IIDA reactions, which are classified as the forward electro density flux. The activation enthalpy ass…

A Molecular Electron Density Theory Study of the Competitiveness of Polar Diels–Alder and Polar Alder-ene Reactions

Indexación: Scopus. Funding: Ministry of Economy and Competitiveness (MINECO) of the Spanish Government, project CTQ2016-78669-P (AEI/FEDER, UE) and Fondecyt (Chile) grant 1180348. Acknowledgments: This research was supported by the Ministry of Economy and Competitiveness (MINECO) of the Spanish Government, project CTQ2016-78669-P (AEI/FEDER, UE) and Fondecyt (Chile) grant 1180348. L.R.D. thanks Fondecyt for continuous support through Cooperación Internacional. M.R.-G. also thanks MINECO for a post-doctoral contract cofinanced by the European Social Fund (BES-2014-068258). The competitiveness of the BF3 Lewis acid (LA) catalyzed polar Diels–Alder (P-DA) and polar Alder-ene (P-AE) reactions …

Understanding the mechanism of non-polar diels-alder reactions. A comparative elf analysis of concerted and stepwise diradical mechanisms

The electron-reorganization along the concerted and stepwise pathways associated with the non-polar Diels-Alder reaction between cyclopentadiene (Cp, 1) and ethylene (2) has been studied using the topological analysis of the electron localization function (ELF) at the B3LYP/6-31G(d) level of theory. ELF results for the concerted mechanism stresses that the electron-reorganization demanded on the diene and ethylene reagents to reach two pseudo-diradical structures is responsible for the high activation energy. A comparative ELF analysis of some relevant points of the non-polar Diels-Alder reaction between Cp and styrene (10) suggests that these concerted mechanisms do not have a pericyclic e…

Alkoxy-styryl DCDHF fluorophores

A photostable dicyanomethylenedihydrofuran fluorophore which contains electron-donating alkoxy groups is described. This chromophore is highly environmentally-sensitive, which is a remarkable property for a fluorescent reporter. Its light excitation also enables, in low viscous solvents, the formation of dark states whose radical or triplet nature is ruled out.

Mechanistic details of the domino reaction of nitronaphthalenes with the electron-rich dienes. A DFT study

Abstract The reaction of 1-nitronaphthalene ( 1 ) with the Danishefsky diene ( 2 ) to give the dihydrophenanthrene derivative 11 has been theoretically studied using DFT methods. This reaction is a domino process that is initialized by a polar Diels–Alder reaction between 1 and 2 to give the formally [2 + 4] cycloadduct 3 . The subsequent concerted elimination of nitrous acid ( 4 ) from 3 yields 11 . Analysis of the global reactivity indices as well as the thermodynamic data for this domino process indicate that while the large electrophilic character of 1 together with the large nucleophilic character of 2 are responsible for the participation of these reagents in a polar Diels–Alder react…

Understanding the Mechanism of Nitrobenzene Nitration with Nitronium Ion: A Molecular Electron Density Theory Study

ChemInform Abstract: Toward an Understanding of the Mechanisms of the Intramolecular [5 + 2] Cycloaddition Reaction of γ-Pyrones Bearing Tethered Alkenes. A Theoretical Study.

The molecular mechanism for the intramolecular [5 + 2] cycloaddition reaction of β-silyloxy-γ-pyrones bearing tethered alkenes has been characterized using ab initio methods. A comparative study for this sort of cycloaddition carried out at different computational levels points out that the B3LYP/6-31G* calculations give similar barriers to those obtained with the MP3/6-31G* level. Analysis of the energetic results shows that the reaction takes place along a stepwise process:  first, the migration of the neighboring silyl group to the carbonyl group of the γ-pyrone takes place to give a weak oxidopyrylium ylide intermediate, which by a subsequent concerted intramolecular [5 + 2] cycloadditi…

A DFT study of the mechanism of Brønsted acid catalysed Povarov reactions

Abstract The molecular mechanism of the Bronsted acid (BA) catalysed Povarov reaction of N -phenyl- C -methoxycarbonyl imine with a methylenecyclopropane (MCP) has been investigated using DFT methods at the MPWB1K/6-31G(d) level. This BA catalysed Povarov reaction is a domino process initialised by the formation of a cationic intermediate which experiences a quick intramolecular Friedel–Crafts reaction yielding the final tetrahydroquinoline. Protonation of the imine nitrogen atom notably increases the electrophilicity of the corresponding species, accelerating the reaction through ionic processes. Analysis of the Parr functions in the initial nucleophilic attack of MCP to the protonated imi…

A molecular electron density theory study of the insertion of CO into frustrated Lewis pair boron-amidines: a [4 + 1] cycloaddition reaction

The insertion of CO into hydrogenated boron-amidine 1 yielding five-membered diazaborolone (5DAB) 3 has been studied within the molecular electron density theory (MEDT) at the DFT ωB97X-D/6-311G(d,p) level. This is a domino process comprised of two consecutive reactions: (i) the dehydrogenation of 1 yielding the frustrated Lewis pair (FLP) boron-amidine 4, which quickly equilibrates with four-membered diazaborolone (4DAB) 2; and (ii) the addition of CO into FLP 4, yielding the final 5DAB 3. Analysis of the Gibbs free energies indicates that the extrusion of H2 demands a high ΔG≠ of 28.6 kcal·mol-1, being endergonic by 6.7 kcal·mol-1. The subsequent addition of CO into FLP 4 presents a low Δ…

Understanding the mechanism of stereoselective synthesis of cyclopentenes via N-heterocyclic carbene catalyzed reactions of enals with enones.

The N-heterocyclic carbene (NHC) catalyzed addition of enals to enones to yield trans-cyclopentenes has been investigated using DFT methods at B3LYP/6-31G** computational level. This NHC catalyzed reaction comprises several steps. The first one is the formation of a Breslow intermediate, which nucleophilically attacks to the conjugated position of the enone to yield an enol-enolate. This second step is responsible for the trans relationship at the final cyclopentene. An intramolecular aldolic condensation allows for the formation of the alkoxy cyclopentane intermediate, that by intramolecular nucleophilic attack on the carbonyl group yields a bicyclic ether. The extrusion of the NHC catalys…

A combined experimental and theoretical study of the thermal [3+2] cycloaddition of carbonyl ylides with activated alkenes

International audience; 4-Benzoyl-3,5-diaryltetrahydrofuran-2,2-dicarbonitriles were first synthesized from 2,2-dicyano-3-aryloxiranes and chalcones at toluene reflux; the 4,5-cis products proved to be predominantly formed and were isolated. Whereas shortened reaction times were observed by using microwave irradiation or catalytic cuprous chloride, no significant stereoselectivity change was in general noticed. Reacting 2,2-dicyano-3-aryloxiranes with 2-cyclopentenone next afforded 3-aryl-4-oxohexahydro-1H-cyclopenta[c]furan-1,1-dicarbonitriles, and the endo stereoisomers were isolated. That no stereoselectivity change was noticed in the presence of cuprous chloride rather suggests an impac…

Understanding the [2n+2n] reaction mechanism between a carbenoid intermediate and CO2

ABSTRACTThe mechanism of the cycloaddition reaction of CO2 with a nucleophilic carbenoid intermediate has been theoretically studied by using the bonding evolution theory (BET) at the B3LYP/6-31G(d) level of theory. BET combines topological analysis of the electron localisation function and catastrophe theory along a reaction path. This cycloaddition reaction is characterised by 16 structural stability domains, associated to the following sequence of catastrophes: C8H9NO4 + CO2: 16-CF†CF†F†CFF†C†C†[FF†]F†FCC†-0: C9H9NO6. Formation of the two new C-C and C-O single bonds evolves after the transition state structure is reached. The high nucleophilic character and the electronic structure of c…

Nature of the ring-closure process along the rearrangement of octa-1,3,5,7-tetraene to cycloocta-1,3,5-triene from the perspective of the electron localization function and catastrophe theory

We analyze the behavior of the energy profile of the ring-closure process for the transformation of (3Z,5Z)-octa-1,3,5,7-tetraene 5 to (1Z,3Z,5Z)-cycloocta-1,3,5-triene 6 through a combination of electron localization function (ELF) and catastrophe theory (CT). From this analysis, concepts such as bond breaking/forming processes, formation/annihilation of lone pairs, and other electron pair rearrangements arise naturally through the reaction progress simply in terms of the different ways of pairing up the electrons. A relationship between the topology and the nature of the bond breaking/forming processes along this rearrangement is reported. The different domains of structural stability of …

Diels-Alderase Catalyzing the Cyclization Step in the Biosynthesis of Spinosyn A

The conversion of putative macrocyclic lactone into the tricyclic compound, as a key step in the biosynthesis of spinosyn A , has been theoretically investigated using DFT methods. The relatively low activation free energy computed for the cyclization process of the actual macrocyclic lactone (21.0 kcal/mol) furnishes a rationalization for a spontaneous ( i.e. nonenzymatically catalyzed) cyclization process in the biosynthesis of spinosyn A . A geometric analysis of putative macrocyclic lactone indicates that a slight strain on the lactone at the active site of the SpnF gene could decrease the activation free energy to ca . 16 kcal/mol. This nonspecific participation of the enzyme, which ac…

A theoretical study of the selectivity for the domino [5+2]/[4+2] cycloadditions of γ-pyrones bearing tethered alkenes with substituted 1,3-butadienes

Abstract Selectivity of the domino [5+2]/[4+2] cycloaddition reactions of a β-silyloxy-γ-pyrone bearing a tethered alkene with two substituted 1,3-butadienes have been theoretically studied at the B3LYP/6-31G∗//AM1 and B3LYP/6-31G∗ computational levels. Analysis of these results allow explaining the regio, stereo and chemoselectivity observed experimentally at these domino reactions. Selectivity outcome is reproduced by these calculations.

An approach to erythrophleum alkaloids. Synthesis of methyl (−)-4-epi-cassamate

Abstract A synthetic approach to Erythrophleum alkaloids, involving as a key-step the regiospecific deprotonation of the ketone 5a, is described.

Theoretical Study of the Elimination Kinetics of Carboxylic Acid Derivatives in the Gas Phase. Decomposition of 2-Chloropropionic Acid

The reaction mechanism for the decomposition of 2-chloropropionic acid in the gas phase to form hydrogen chloride, carbon monoxide, and acetaldehyde has been theoretically characterized. Analytical gradients have been used by means of AM1 and PM3 semiempirical procedures and ab initio methods at HF and DFT (BLYP) levels with the 6-31G** basis set. The correlation effects were also included by using the perturbational approach at the MP2 level with the 6-31G** and 6-31++G** basis sets and the variational approach at the CISD/6-31G** level and by means of MCSCF wave functions with a (6,6) complete active space and the 6-31G** basis set. The global potential energy surface has been studied, an…

Lewis acid induced [4+3] cycloadditions of 2-silyloxyacroleins. Insights on the mechanism from a DFT analysis

The mechanism for the Lewis acid induced [4+3] cycloadditions of 2-(trimethylsilyloxy)acrolein with furan has been examined here through DFT calculations at B3LYP/6-31G* level. The mechanism is a three-step process initialized by the nucleophilic attack of furan to the β-conjugated position of acrolein yielding a zwitterionic intermediate. The key step on the formation of the seven-membered ring is the electrophilic attack of the furan residue to the carbonyl carbon in this intermediate. The endo selectivity experimentally observed is reproduced by the calculations.

ChemInform Abstract: General and Theoretical Aspects of the Metal Enolates

1 General Aspects 2 Structure of the Metal Enolates 3 Spectroscopy of the Metal Enolates 4 Reactivity of the Metal Enolates 5 Acknowledgments Keywords: general and theoretical aspects of metal enolates; metal enolate structure; calcium and magnesium enolates; spectroscopy of metal enolates - NMR spectroscopy; UV spectroscopy; enolate, applied to anionic structure with two carbon atoms bound through double bond; IR spectroscopy; generalized gradient approximation (GGA-DFT) for adsorption modes of acetone

An Understanding of the Electrophilic/Nucleophilic Behavior of Electro-Deficient 2,3-Disubstituted 1,3-Butadienes in Polar Diels−Alder Reactions. A Density Functional Theory Study

The electrophilic/nucleophilic behavior of dimethyl 2,3-dimethylenesuccinate 1, an electron-deficient 2,3-disubstituted 1,3-butadiene, in polar Diels-Alder reactions has been studied using DFT methods at the B3LYP/6-31G(d) level of theory. The electronic nature of bonding of the transition structures involved in the cycloaddition reactions of the diene 1 toward the nucleophilically activated dienophile 6 and the strong electrophilically activated dienophile 7 has been carefully examined within the natural bond orbital (NBO) and the topological analysis of the electron localization function (ELF) frameworks. Additionally, a study of the global electrophilicity pattern of the reagents at the …

A DFT Study of the Conversion of Ptaquiloside, a Bracken Fern Carcinogen, to Pterosin B in Neutral and Acidic Aqueous Medium

The conversion of ptaquiloside (PtQ), a bracken fern (Pteridium aquilinum) carcinogen, to pterosin B (PtB), which is involved in the underlying mechanisms of PtQ genotoxicity and carcinogenicity, has been theoretically studied in aqueous neutral (AN) and acid (AA) media, using DFT methods at the PCM(water)-B3LYP/6-31G(d)//B3LYP/6-31G(d) computational level. The β-elimination of glucose in AN and four reactive channels (A-D) defined by as many protonation sites in PtQ were calculated. Activation enthalpy decreases (from 42.0 to 12.6 kcal mol−1) in AA relative to AN suggesting protic catalysis. The most favoured channel A started with protonation of the tertiary O15 hydroxyl of PtQ and SN1 wa…

Calculation of the rate constants for hydrogen abstraction reactions by Hydroperoxyl radical from Methanol, and the investigation of stability of CH3OH.HO2 complex

Abstract Master equation (ME) with Lennard-Jones potential utilized to simulate the collision between CH3OH and HO2 radical in the presence of bath gas. The reaction mechanism explored through the lowest doublet potential energy surface at CCSD(T)/aug-cc-pVTZ//B3LYP/aug-cc-pVTZ level of theory that is barrierless and forms shallow energized intermediate at the entrance channel. The investigation of the fractional population showed that lifetime of CH3OH.HO2 intermediate (INT*) is fairly short due to its shallow depth, and at the low temperature, most reaction takes place by re-dissociation back to reactants and also when the pressure is high enough, the INT* is thermalized and comes into eq…

Toward an understanding of the acceleration of Diels-Alder reactions by a pseudo-intramolecular process achieved by molecular recognition. A DFT study.

The pseudo-intramolecular Diels−Alder (DA) reaction between a 2-substituted furan (1) and a N-maleimide derivative (2) has been analyzed using DFT methods. Formation of two hydrogen bonds between the appendages on furan and maleimide derivatives favors thermodynamically the formation of a molecular complex (MC1) through an efficient molecular recognition process. The large enthalpy stabilization associated with the molecular recognition overcomes the unfavorable activation entropy associated with the bimolecular process. As a consequence, the subsequent DA reaction is clearly accelerated through a pseudo-intramolecular process.

Better understanding of the ring-cleavage process of cyanocyclopropyl anionic derivatives. A theoretical study based on the electron localization function.

[reaction: see text] Theoretical calculations at the B3LYP/6-31+G(d), MP2/6-31+G(d), and G3(MP2) levels have been carried out to understand the alternative reaction pathways (the cyclopropyl ring cleavage (RC) and the retrocycloaddition reaction (rCA)) of a constrained tricyanocyclopropyl anionic derivative. The more energetically favorable path is found to be the RC process, a formally "forbidden" rearrangement (Leiviers, M.; Tam, I.; Groves, K.; Leung, D.; Xie, Y.; Breslow, R. Org. Lett. 2003, 5, 19, 3407) yielding an allylic anion system via a concerted transition structure, in agreement with experimental outcomes. rCA is more energetically favorable along a two-stage mechanism, via an i…

Density functional theory study of the 5-pyrrolidin-2-yltetrazole-catalyzed aldol reaction

Abstract The replacement of the carboxylic acid functionality with a tetrazolic acid in the proline-catalyzed asymmetric aldol reaction between acetone and trimethylacetaldehyde has been studied using DFT methods at the B3LYP/6-31G** computational level. For the C–C bond-formation step, four reactive channels corresponding to the syn and anti arrangement of the enamine and the re and si attack modes have been analyzed. The B3LYP/6-31G** results allowed us to explain the stereoselectivity and the increase in reactivity relative to the proline-catalyzed process in DMSO.

A molecular electron density theory study of the Lewis acid–catalyzed decomposition reaction of nitroethyl benzoate using aluminum derivatives

The carbenoid-type reactivity of simplest nitrile imine from a molecular electron density theory perspective

Abstract The [3 + 2] cycloaddition (32CA) reactions of the simplest nitrile imine with ethylene and electrophilic dicyanoethylene have been studied within the Molecular Electron Density Theory (MEDT) with the aim of characterising its reactivity. Topological analysis of the electron localisation function of NI shows that it has a carbenoid structure. The activation energy of the 32CA reaction of the simplest nitrile imine with dicyanoethylene is 5.6 kcal mol−1 lower than that involving ethylene, in agreement with the high polar character of the former reaction. Bonding Evolution Theory accounts for the cb-type reactivity of nitrile imine. Along the more favourable ortho regioisomeric path a…

The tandem Diels-Alder reaction between acetylenedicarboxyaldehyde and N,N'-dipyrrolylmethane. An ab initio study of the molecular mechanisms

Abstract An extensive exploration at RHF/3-21G and RHF/6-31G ∗ levels of the potential energy surface for the tandem cycloaddition of acetylenedicarboxyaldehyde to N,N'-dipyrrolylmethane allows us to characterize the reaction pathways and the associated stationary points. The formation of the pincer and/or domino adducts can be described as a stepwise mechanism. The first step, associated with an intermolecular [4 + 2] cycloaddition, is the rate determining step and an azanorbornadiene intermediate is obtained. The second step is an intramolecular [4 + 2] cycloaddition. The formation of the pincer adduct is the step which kinetically controls the global process, due to the low barrier heigh…

Towards an Understanding of the Polar Diels–Alder Reactions of Nitrosoalkenes with Enamines: A Theoretical Study

The polar Diels–Alder reactions of nitrosoalkenes with enamines have been studied using DFT methods at the B3LYP/6-31G* level of theory. These Diels–Alder reactions are characterized by a nucleophilic attack of the enamine at the conjugated position of the nitrosoalkene with concomitant ring-closure. The reactions present a total regioselectivity and a large endo selectivity. The analysis, based on the global electrophilicity of the reagents in the ground state, the natural bond orbital (NBO), and the topological analysis of the electron localization function (ELF) in the endo transition state (TS) and “halfway” along the IRC between the TS and cycloadduct, correctly explain the polar natur…

Experimental and theoretical investigations for the tandem alkylation–isomerization reactions between unsaturated carboxylic acids and allyl halides

Abstract—Alkylation of dienediolates from unsaturated carboxylic acids with allylic halides when followed by solventless thermaltreatment at 150 to 2008C afford rearranged products on a trend highly dependent on the acarbon substitution. Thus, 2,2-bisallylated acidswith H atoms at C-2 lead to its 1,3-shift, whereas 2-methyl-2,2-bisallylated acids lead to the corresponding Cope rearrangement product. Inthe latter case, this tandem allylation-Cope reaction lead, in a highly regio and diastereoselective way, to products not accessible from directalkylation. B3LYP/6-31G p energies for the compounds involved at these isomerizations are in reasonable agreement with the experiments,allowing to exp…

An AM1 theoretical study on the effect of Zn2+ Lewis acid catalysis on the mechanism of the cycloaddition between 3-phenyl-1-(2-pyridyl)-2-propen-1-one and cyclopentadiene

Abstract The mechanism of the Diels–Alder reaction between 3-phenyl-1-(2-pyridyl)-2-propen-1-one and cyclopentadiene has been investigated with the AM1 semiempirical method. Stationary points for two reactive channels, endo - cis and exo - cis , have been characterized. The role of the Lewis acid catalyst has been modeled taking into account the formation of a complex between Zn 2+ and the carbonyl oxygen atom and the pyridyl nitrogen atom of the 3-phenyl-1-(2-pyridyl)-2-propen-1-one system with and without the presence of two molecules of water around the cation. The mechanism of the uncatalyzed reaction corresponds to a concerted process, but in the presence of Lewis acid catalyst the mec…

A Molecular Electron Density Theory Study of the Synthesis of Spirobipyrazolines through the Domino Reaction of Nitrilimines with Allenoates

The reaction of diphenyl nitrilimine (NI) with methyl 1-methyl-allenoate yielding a spirobipyrazoline has been studied within molecular electron density theory (MEDT) at the MPWB1K/6-311G(d) computational level in dichloromethane. This reaction is a domino process that comprises two consecutive 32CA reactions with the formation of a pyrazoline intermediate. Analysis of the relative Gibbs free energies indicates that both 32CA reactions are highly regioselective, the first one being also completely chemoselective, in agreement with the experimental outcomes. The geometries of the TSs indicate that they are associated to asynchronous bond formation processes in which the shorter distance invo…

On Transition Structures for Hydride Transfer Step in Enzyme Catalysis. A Comparative Study on Models of Glutathione Reductase Derived from Semiempirical, HF, and DFT Methods

As a model of the chemical reactions that take place in the active site of gluthatione reductase, the nature of the molecular mechanism for the hydride transfer step has been characterized by means of accurate quantum chemical characterizations of transition structures. The calculations have been carried out with analytical gradients at AM1 and PM3 semiempirical procedures, ab initio at HF level with 3-21G, 4-31G, 6-31G, and 6-31G basis sets and BP86 and BLYP as density functional methods. The results of this study suggest that the endo relative orientation on the substrate imposed by the active site is optimal in polarizing the C4-Ht bond and situating the system in the neighborhood of the…

Theozyme for antibody aldolases. Characterization of the transition-state analogueElectronic supplementary information (ESI) available: MP2/6-31G** energies, imaginary frequencies and cartesian coordinates. See http://www.rsc.org/suppdata/ob/b2/b209636f/

A theozyme for antibody aldolases has been studied at the MP2/6-31G** computational level. Formation of two cooperative hydrogen-bonds between the acidic hydrogen atoms of the enamine and of a methanol molecule with the oxygen atom of the aldol acceptor markedly favors the C–C bond-formation associated with the aldol reaction. A comparative analysis of the geometry, the charge distribution and the shape of the molecular electrostatic potential of the transition structure (TS) with the covalent adduct, resulting from the reaction of methylamine and the β-diketone used as a hapten allows us to characterize the transition-state analogue (TSA) generated at immunization. This finding allows us t…

Polar [3 + 2] cycloaddition of ketones with electrophilically activated carbonyl ylides. Synthesis of spirocyclic dioxolane indolinones

International audience; The [3 + 2] cycloaddition reaction between carbonyl ylides generated from epoxides and ketones (ethyl pyruvate, ethyl phenylglyoxylate, isatin, N-methylisatin and 5-chloroisatin) to give substituted dioxolanes and spirocyclic dioxolane indolinones was investigated. The effect of microwave irradiation on the outcome of the reaction was studied. The thermal reaction between 2,2-dicyano-3-phenyloxirane and N-methylisatin was theoretically studied using DFT methods. This reaction is a domino process that comprises two steps. The first is the thermal ring opening of the epoxide to yield a carbonyl ylide intermediate, whereas the second step is a polar [3 + 2] cycloadditio…

The domino reaction between 4,6-dinitrobenzofuroxan and cyclopentadiene. Insights on the nature of the molecular mechanism

Abstract The molecular mechanism of the domino reaction between 4,6-dinitrobenzofuroxan, 1 , and cyclopentadiene, Cp, to give the adduct 11 is examined through density functional theory (DFT) calculations at B3LYP/6-31G* level. This domino reaction comprises two consecutive formally [4+2] cycloadditions. The first one is a two-center addition initialized by the nucleophilic attack of Cp to the more electrophilic center of 1 . The subsequent cyclization can take place along two competitive channels associated to the formation of a second C–C bond yielding the formally [2+4] cycloadduct 9 , or a C–O bond yielding the formally [4+2] cycloadduct 10 . The second cycloaddition is a stepwise proce…

Lewis Acid-Catalyzed [4 + 3] Cycloaddition of 2-(Trimethyl Silyloxy)acrolein with Furan. Insight on the Nature of the Mechanism from a DFT Analysis

[reaction: see text]. The mechanism for the Lewis acid-catalyzed [4 + 3] cycloaddition of 2-(trimethylsilyloxy)acrolein 1 with furan 2 has been studied at the B3LYP/6-31G level. This reaction is a three-step process that is initialized by the nucleophilic attack of 2 to the beta-conjugated position of 1 to give a zwitterionic intermediate IN1. The key step on the formation of the seven-membered ring is the electrophilic attack of the furan residue to the electrophilically activated carbonyl carbon at this intermediate.

ChemInform Abstract: Remarkable Effect of Lithium Bromide in the Enantioselective Protonation with α-Sulfinyl Alcohols.

Abstract The favourable effect of lithium bromide enhancing the facial enantioselectivity in the protonation of methyl tetralone enolate with α-sulfinyl alcohols is described. Theoretical calculations allow to propose a model to explain the stereochemical course of the protonation reaction.

Molecular Electron Density Theory: A Modern View of Reactivity in Organic Chemistry

A new theory for the study of the reactivity in Organic Chemistry, named Molecular Electron Density Theory (MEDT), is proposed herein. MEDT is based on the idea that while the electron density distribution at the ground state is responsible for physical and chemical molecular properties, as proposed by the Density Functional Theory (DFT), the capability for changes in electron density is responsible for molecular reactivity. Within MEDT, the reactivity in Organic Chemistry is studied through a rigorous quantum chemical analysis of the changes of the electron density as well as the energies associated with these changes along the reaction path in order to understand experimental outcomes. St…

Understanding the mechanisms of [3+2] cycloaddition reactions. The pseudoradical versus the zwitterionic mechanism

Abstract Analysis of 12 three-atom-components (TACs) participating in [3+2] cycloaddition (32CA) reactions towards ethylene and acetylene allows establishing good correlations between the pseudodiradical character, the hardness η, and the nucleophilicity N index of the TAC with the feasibility of these non-polar reaction. These results allow the introduction of the pr index, which comprises the two aforementioned DFT reactivity indices. The increase of the pr index for an allylic-type TAC goes accompanied by a linear decrease of the activation enthalpy of the reaction. The present study makes it possible to establish a useful classification of 32CA reactions into zw-type reactions involving…

Theoretical Study on the Molecular Mechanism of the Domino Cycloadditions between Dimethyl Acetylenedicarboxylate and Naphthaleno- and Anthracenofuranophane

AM1, B3LYP/6-31G//AM1, and B3LYP/6-31G computational studies were performed to select the reaction pathway controlling the reactions between dimethyl acetylenedicarboxylate (DMAD) and two furanophanes, naphthalenofuranophane and anthracenofuranophane. For these domino reactions, several pathways have been characterized on the potential energy surface corresponding to two consecutive cycloadditions. The first step corresponds to a [4 + 2] intermolecular cycloaddition of DMAD with the furan ring or with the naphthalene or anthracene ring of both furanophane systems to yield an oxabicyclo[2.2.1]heptadiene or a bicyclo[2.2.2]octadiene intermediate, respectively. The second step corresponds to […

Aziridination of Aromatic Aldimines Through Stabilized Ammonium Ylides: A Molecular Electron Density Theory Study

Unveiling the Different Chemical Reactivity of Diphenyl Nitrilimine and Phenyl Nitrile Oxide in [3+2] Cycloaddition Reactions with (R)-Carvone through the Molecular Electron Density Theory

The [3+2] cycloaddition (32CA) reactions of diphenyl nitrilimine and phenyl nitrile oxide with (R)-carvone have been studied within the Molecular Electron Density Theory (MEDT). Electron localisation function (ELF) analysis of these three-atom-components (TACs) permits its characterisation as carbenoid and zwitterionic TACs, thus having a different reactivity. The analysis of the conceptual Density Functional Theory (DFT) indices accounts for the very low polar character of these 32CA reactions, while analysis of the DFT energies accounts for the opposite chemoselectivity experimentally observed. Topological analysis of the ELF along the single bond formation makes it possible to characteri…

A molecular electron density theory study of the [3 + 2] cycloaddition reaction of nitrones with strained allenes

Indexación: Scopus. The [3 + 2] cycloaddition (32CA) reaction of C-phenyl-N-tert-butylnitrone with 1,2-cyclohexadiene (CHDE), a strained allene, has been studied within Molecular Electron Density Theory (MEDT) at the DFT B3LYP/6-311G(d,p) computational level. This non-polar 32CA reaction, which takes place through a non-concerted two-stage one-step mechanism, proceeds with a moderate Gibbs free activation energy of 22.7 kcal mol-1, and presents low stereo- and regioselectivities. The reaction begins by the creation of a pseudoradical center at the central carbon of the strained allene with a relatively low energy cost, which immediately promotes the formation the first C-C single bond. This…

A DFT Analysis of the Strain-Induced Regioselective[2+2]Cycloaddition of Benzyne Possessing Fused Four-Membered Ring

A density functional theory study of the regio- and stereoselectivity of the 1,3-dipolar cycloaddition of C-methyl substituted pyrazinium-3-olates with methyl acrylate and methyl methacrylate

Abstract A DFT [B3LYP/6-31G(d)] study was carried out on the 1,3-dipolar cycloaddition (13DC) reactions of multi C-methyl substituted pyrazinium-3-olates with methyl acrylate (MA) and methyl methacrylate (MMA). Thermodynamic and kinetic parameters of the possible endo/exo stereoisomeric and 6-ester/7-ester regioisomeric pathways have been determined. The skeleton rearrangement of the 6-exo [3 + 2] cycloadducts into the [4 + 2] adducts is also considered. The electrophilic, P k + , and nucleophilic, P k - , Parr functions are used to have better understanding of the regioselectivity of these 13DC reactions. In all cases the exo pathways are more favourable compared to the endo alternatives. …

Mechanism of triplet photosensitized Diels-Alder Reaction between indoles and cyclohexadienes: theoretical support for an adiabatic pathway.

Diels-Alder reactions between indoles (InHs) and 1,3-cyclohexadienes (CHDs) were achieved by using aromatic ketones as photosensitizers. For instance, irradiation of deaerated dichloromethane solutions containing benzoylthiophene (BT, 1 mM), indole (20 mM), and phellandrene (40 mM), in the presence of an acylating agent, led to the N-acetylated Diels-Alder cycloadduct in 46% yield (endo:exo ratio of 1.8:1). Energy transfer from the BT triplet to the CHD gave rise to diene dimers as byproducts. Several combinations of CHDs, InHs, and aromatic ketones were tested; the Diels-Alder reaction was found to be a general process, except when the indole nucleus was substituted at position 2 or 7 and …

Quantitative characterization of the global electrophilicity power of common diene/dienophile pairs in Diels–Alder reactions

Abstract The global electrophilicity power, ω, of a series of dienes and dienophiles commonly used in Diels–Alder reactions may be conveniently classified within a unique relative scale. Useful information about the polarity of transition state structures expected for a given reaction may be obtained from the difference in the global electrophilicity power, Δω, of the diene/dienophile interacting pair. Thus the polarity of the process can be related with non-polar (Δω small, pericyclic processes) and polar (Δω big, ionic processes) mechanisms.

Density functional theory study of the mechanism of the proline-catalyzed intermolecular aldol reaction

Transition structures associated with the C-C bond-formation step of the proline-catalyzed intermolecular aldol reaction between acetone and isobutyraldehyde have been studies using density functional theory methods at the B3LYP/6-31G** computational level. A continuum model has been selected to represent solvent effects. For this step, which is the stereocontrolling and rate-determining step, four reactive channels corresponding to the syn and anti arrangement of the active methylene of the enamine relative to the carboxylic acid group of l-proline and the re and si attack modes to both faces of the aldehyde carbonyl group have been analyzed. The B3LYP/6-31G** energies are in good agreemen…

Nonlocal (Pair Site) Reactivity from Second-Order Static Density Response Function:  Gas- and Solution-Phase Reactivity of the Acetaldehyde Enolate as a Test Case

A nonlocal (pair site) reactivity scheme is developed and tested. The theory is cast in terms of the first-order Fukui response function f(r,r‘), previously proposed by Fuentealba and Parr [J. Chem. Phys. 1991, 94, 5559]. A change of variables is introduced by using the softness s(r) and t(r) = [∂s(r)/∂N]υ(r) (the variation of softness with respect to the changes in the total number of electrons N at constant external potential υ(r)) that leads to a simple expression for the variation of the Fukui function at site k, namely = − for an electrophilic attack. The first term describes a local contribution, proportional to the variation of the electrostatic potential that can be induced, for exa…

A DFT study of the role of the Mg complex formation on the mechanism of the 1,3-dipolar cycloadditions of benzonitrile oxides with acryloylpyrazolidinone

Abstract The role of the Mg complex formation on the mechanism, the reaction rate and regioselectivity of the 1,3-dipolar cycloaddition (13DC) reactions of benzonitrile oxides (BNOs) towards electron-deficient acryloylpyrazolidinones has been theoretically studied using DFT methods at the 6-31G* level. These 13DC reactions have asynchronous concerted mechanism with a non-polar character. These cycloadditions present a slight 5-regioselectivity induced by a steric repulsion between the phenyl substituent of the BNOs and the pyrazolidinone appendage present on the acryloyl derivative, which increases with the formation of the bulky Mg–acryloylpyrazolidinone complex. The present DFT study poin…

Unveiling the Chemo‐ and Regioselectivity of the [3+2] Cycloaddition Reaction between 4‐Chlorobenzonitrile Oxide and β‐Aminocinnamonitrile with a MEDT Perspective**

DFT Study of the Molecular Mechanism of Lewis Acid Induced [4 + 3] Cycloadditions of 2-Alkylacroleins with Cyclopentadiene

The mechanism of the Lewis acid (AlCl(3)) induced [4 + 3] cycloaddition of 2-methylacrolein with cyclopentadiene (Cp) [ J. Am. Chem. Soc. 2004, 126, 2692] has been examined here through DFT calculations at the MPW1K(DCM)/6-31+G** level. Formation of these seven-membered carbocycles is a domino process that comprises three consecutive reactions. The first one is a polar Diels-Alder reaction that is initialized by the nucleophilic attack of Cp to the beta-conjugated position of acrolein, yielding the formation of the endo and exo [4 + 2] cycloadducts. The corresponding LA-[4 + 2] cycloadduct complexes equilibrate through a skeleton rearrangement with a low free activation energy with two seve…

Unraveling the kinetics and molecular mechanism of gas phase pyrolysis of cubane to [8]annulene

The kinetic and electron density flows are studied theoretically for the gas phase pyrolysis of cubane via its cage opening to reach bicyclooctatriene and then thermal rearrangement of bicyclooctatriene to produce [8]annulene which is the experimentally observed major product. The observed kinetic data at the MN15-L/maug-cc-pVTZ level of theory were in good agreement with the experimental results as compared to the CBS-QB3 method. The cage opening and the thermal rearrangement steps at the experimentally employed temperature of 520 K were exergonic and exothermic. The atmospheric rate constants calculated by means of the RRKM theory show that the cage opening is the rate-determining step. T…

Origin of the synchronicity in bond formation in polar Diels-Alder reactions: an ELF analysis of the reaction between cyclopentadiene and tetracyanoethylene

[EN] The origin of the synchronicity in C-C bond formation in polar Diels-Alder (P-DA) reactions involving symmetrically substituted electrophilic ethylenes has been studied by an ELF analysis of the electron reorganization along the P-DA reaction of cyclopentadiene (Cp) 4 with tetracyanoethylene (TCE) 10 at the B3LYP/6-31G* level. The present study makes it possible to establish that the synchronicity in C-C bond formation in P-DA reactions is controlled by the symmetric distribution of the electron-density excess reached in the electrophile through the charge transfer process, which can be anticipated by an analysis of the spin electron-density at the corresponding radical anion. The ELF …

Theoretical study on the mechanism of the domino reactions of tertiary α-cyano-enamines and dimethyl acetylenedicarboxylate

Abstract The mechanisms of the domino reaction between dimethyl acetylenedicarboxylate, 1 , and 2-( N , N -dimethylamino)acrylonitrile, 2 , and these in presence of acrylonitrile have been theoretically studied using ab initio methods. These domino reactions comprise several pericyclic-type reactions. The geometrical and electronic analysis of the HF/6-31G ∗ transition structures and intermediates allows characterizing the processes that take place along these domino reactions. B3LYP/6-31G ∗ energetic results are in agreement with the experimental outcomes.

A DFT study of the [3 + 2] versus [4 + 2] cycloaddition reactions of 1,5,6-trimethylpyrazinium-3-olate with methyl methacrylate.

The reaction between 1,5,6-trimethylpyrazinium-3-olate and methyl methacrylate (MMA) yielding a lactone-lactam has been studied using the DFT method at the B3LYP/6-31G(d) level. It is concluded that formation of the lactone-lactam is a domino process involving three consecutive reactions: (i) a 1,3-dipolar cycloaddition (13DC) reaction between the pyrazinium-3-olate and MMA yielding a [3 + 2] cycloadduct (CA); (ii) a skeletal rearrangement, which converts the [3 + 2] CA into a formal [4 + 2] CA, possessing a diazabicyclo[2.2.2]octane structure; and finally, (iii) an S(N)2 reaction, promoted by halide anion, with concomitant nucleophilic attack of the created carboxylate anion on an iminium …

Atmospheric Oxidation Reactions of Methyl Salicylate as Green Leaf Volatiles by OH Radical: Theoretical Kinetics and Mechanism

A density functional theory study for the Diels–Alder reaction between N-acyl-1-aza-1,3-butadienes and vinylamines. Lewis acid catalyst and solvent effects

Abstract The molecular mechanism for the Diels–Alder reaction of N-acyl-1-aza-1,3-butadiene with dimethylvinylamine has been studied using density functional theory methods. This cycloaddition is the nucleophilic attack of the vinylamine to the conjugate position of the unsaturated acyl imine with concomitant ring-closure. The presence of a Lewis acid catalyst coordinated to the acyl oxygen atom decreases markedly the activation energy associated to the nucleophilic attack. This results from an increasing of the electrophilicity of the 1-aza-1,3-butadiene that shift the mechanism from a highly asynchronous concerted process to a polar stepwise one.

Understanding the kinetic solvent effects on the 1,3-dipolar cycloaddition of benzonitrile N-oxide: a DFT study

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, ISSN : 0894-3230, DOI : 10.1002/poc.1858, Issue : 7, Volume : 24, pp. 611 – 618, JUILLET 2011.

Experimental and theoretical investigations for the regio and stereoselective transformation of trans 1,2,3-trisubstituted aziridines into trans oxazolidin-2-ones

The regio and stereoselective transformation of trans 1,2,3-trisubstituted aziridines into trans oxazolidin-2-ones takes place in good yield. However, the cis configuration at C2 and C3 in monocyclic aziridines is a limiting factor for this transformation. Ab initio calculations show that while the ring-opening process assisted by iodide is regioselective, the subsequent ring-closure is responsible for the retention of the configuration at the trans oxazolidin-2-ones. The larger energy found for the ring-closure process for the cis aziridines accounts for the non-formation of the cis oxazolidin-2-ones.

Analysis of mebendazole binding to its target biomolecule by laser flash photolysis

[EN] Mebendazole (MBZ) and related anticancer benzimidazoles act binding the beta-subunit of Tubulin (TU) before dimerization with alpha-TU with subsequent blocking microtubule formation. Laser flash photolysis (LFP) is a new tool to investigate drug-albumin interactions and to determine binding parameters such as affinity constant or population of binding sites. The aim of this study was to evaluate the interactions between the nonfluorescent mebendazole (MBZ) and its target biomolecule TU using this technique. Before analyzing the MBZ@TU complex it was needed to determine the photophysical properties of MBZ triplet excited state ((3)MBZ*) in different media. Hence, 3MBZ* showed a transien…

Quantitative Characterization of the Local Electrophilicity of Organic Molecules. Understanding the Regioselectivity on Diels−Alder Reactions

Regional electrophilicity at the active sites of the reagents involved in polar Diels−Alder processes may be described on a quantitative basis using an extension of the global electrophilicity inde...

Aromaticity in Pericyclic Transition State Structures? A Critical Rationalisation Based on the Topological Analysis of Electron Density

The nature of the electron delocalisation pattern within a cyclic structure, i. e. the aromatic character, is examined for six-membered pseudocyclic transition state structures (TSs) involved in five representative examples of so-called pericyclic reactions. Results of the electron localisation function (ELF) and the quantum theory of atoms in molecules (QTAIM) analyses of the electron density evidence that in four of the cases, at least one pair of atoms are not bound at the TS configuration, thus precluding a possible cyclic conjugation. These findings make it possible to rule out the aromatic character of these TSs. High values of the synchronicity Sy index at the TSs contrast with the b…

Theoretical study of the molecular mechanism of the domino pathways for squarate ester sequential reactions

Understanding the mechanism and regioselectivity of the copper(i) catalyzed [3 + 2] cycloaddition reaction between azide and alkyne: a systematic DFT study

The copper(I) catalyzed azide–alkyne [3 + 2] cycloaddition (32CA) reaction and its uncatalyzed version have been studied for systematic understanding of this relevant organic transformation, using DFT calculations at the B3LYP/6-31G(d) (LANL2DZ for Cu) computational levels. In the absence of a copper(I) catalyst, two regioisomeric reaction paths were studied, indicating that the 32CA reaction takes place through an asynchronous one-step mechanism with a very low polar character. The two reactive channels leading to 1,4- and 1,5-regisomer present similar high activation energies of 18.84 and 18.51 kcal mol−1, respectively. The coordination of copper(I) to alkyne produces relevant changes in …

Understanding the origin of the asynchronicity in bond-formation in polar cycloaddition reactions. A DFT study of the 1,3-dipolar cycloaddition reaction of carbonyl ylides with 1,2-benzoquinones

The origin of the asynchronicity in bond-formation in polar cycloadditions has been studied by an ELF analysis of the electron reorganisation along the 1,3-dipolar cycloaddition of Padwa's carbonyl ylide 4 with the 1,2-benzoquinone 8. This reaction presents an unexpected asynchronous bond-formation, which is initialised through the nucleophilic attack of Padwa's carbonyl ylide on the carbonyl oxygen atom of the strongly electrophilically activated 1,2-benzoquinone. The present study allows for the establishment that along an asynchronous bond-formation, the more favourable two-center interaction begins at the most electrophilic center, which is the center with the highest spin density achie…

Understanding the role of the Lewis acid catalyst on the 1,3-dipolar cycloaddition of N-benzylideneaniline N-oxide with acrolein: a DFT study

Abstract The Lewis acid (LA) catalyzed 1,3-dipolar cycloaddition of N -benzylideneaniline N -oxide with acrolein has been studied using DFT calculations. Coordination of AlCl 3 to the acrolein oxygen atom produces a drastic change in the mechanism along the more favorable meta reactive channel. The process is characterized by a strong nucleophile/electrophile interaction allowing the formation of a zwitterionic intermediate, a Michael-type addition. The subsequent ring closure constitutes the rate-determining step. The energies obtained with the inclusion of solvent effect by means of the polarizable continuum model are in good agreement with experimental findings. Analysis of the global an…

Quantitative characterization of the global electrophilicity pattern of some reagents involved in 1,3-dipolar cycloaddition reactions

Abstract The global electrophilicity power, ω, of a series of dipoles and dipolarophiles commonly used in 1,3-dipolar cycloadditions may be conveniently classified within a unique relative scale. The effects of chemical substitution on the electrophilicity of molecules have been evaluated using a representative set of electron-withdrawing and electron-releasing groups for a series of dipoles including nitrone, nitrile oxide and azide derivatives. The absolute scale of electrophilicity is used to rationalize the chemical reactivity of these species as compared to the static reactivity pattern of the reagents involved in the Diels–Alder reactions.

A combined experimental and theoretical study of the unimolecular elimination kinetics of 2-alkoxypropionic acids in the gas phase

Abstract The reaction mechanism associated with the decomposition of three 2-alkoxypropionic acids (2-methoxy-, 2-ethoxy- and 2-isopropoxypropionic acid) in gas phase to form acetaldehyde, carbon monoxide, and the corresponding alcohol has been analyzed by a combination of experimental and theoretical studies. The kinetics of these systems were determined in a static system over the temperature and pressure range of 301.2–370.7°C and 61–190 Torr, respectively, in seasoned vessel, with the free-radical inhibitor cyclohexene. The experimental data show that these decompositions are homogeneous, unimolecular and follow a first-order rate law. A detailed characterization, at MP2/6-31G** computa…

A Study of the Effects of the Lewis Acid Catalysts on Oxa‐Diels‐Alder Reactions through Molecular Electron Density Theory

A Theoretical Study of the Reaction between Cyclopentadiene and Protonated Imine Derivatives:  A Shift from a Concerted to a Stepwise Molecular Mechanism

The reaction between cyclopentadiene and protonated pyridine-2-carboxaldehyde imine derivatives has been studied by using Hartree-Fock (HF) and B3LYP methods together with the 6-31G basis set. The molecular mechanism is stepwise along an inverted energy profile. This results from the protonation on both nitrogen atoms of the imine group and the pyridine framework. The first step corresponds to the nucleophilic attack of cyclopentadiene on the electron-poor carbon atom of the iminium cation group to give an acyclic cation intermediate, and the second step is associated with the ring closure of this intermediate via the formation of a C-N single bond yielding the final cycloadduct. Two reacti…

The role of the transfer group in the intramolecular [5+2] cycloadditions of substituted β-hydroxy-γ-pyrones: a DFT analysis

The intramolecular [5+2] cycloaddition reactions of a series of 3-OR (R=SiMe3, H, CHO, Me) substituted β-hydroxy-γ-pyrones bearing tethered alkenes were studied using DFT methods at the B3LYP/6–31G* level. The role of the transfer R group was analyzed considering two alternative channels: (i) in channel a the process is initialized by the transfer of the R group with formation of an oxidopyrylium ylide intermediate, which is followed of an intramolecular [5+2] cycloaddition; (ii) in channel b, the process is initialized by the intramolecular [5+2] cycloaddition on the γ-pyrone followed by the transfer of the R group. Copyright © 2005 John Wiley & Sons, Ltd.

A molecular electron density theory study of the participation of tetrazines in aza-Diels–Alder reactions

The reactions of eight tetrazines of increased electrophilic character with nucleophilic tetramethyl ethylene (TME) and with electrophilic tetracyanoethylene (TCE) have been studied using Molecular Electron Density Theory. These reactions are domino processes comprising an aza-Diels&ndash;Alder (ADA) reaction followed by an extrusion of molecular nitrogen, yielding a dihydropyridazine. Analysis of the conceptual DFT (CDFT) indices showed an increase of the electrophilicity and a decrease of the nucleophilicity of tetrazines with an increase of the electron-withdrawing character of the substituent. A very good correlation between the global electron density transfer at the transition structu…

Why do Electron-Deficient Dienes React Rapidly in Diels?Alder Reactions with Electron-Deficient Ethylenes? A Density Functional Theory Analysis

The Diels−Alder reaction of the electron-deficient (ED) dimethyl 2,3-dimethylenesuccinate with two electron-rich (ER) and two ED ethylenes has been studied at the B3LYP/6-31G* level of theory. The analysis of the geometry and electronic structure of the transition state of the reaction with the ED dimethyl 2-methylenemalonate along with the analysis of the global and local electrophilicity indices of the reagents provide an explanation of the participation of this ED diene as nucleophile against powerful electrophiles in polar Diels−Alder reactions. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

The role of the trifluoromethyl group in reactivity and selectivity in polar cycloaddition reactions. A DFT study

Abstract The role of the trifluoromethyl group in reactivity, regio-, and stereoselectivity in cycloaddition reactions has been analyzed by studying the 1,3-dipolar cycloaddition (13DC) reactions of nitrone 4 with 3,3,3-trifluoro-1-nitropropene 7b and 3,3,3-trifluoro-2-nitropropene 14 using density functional theory (DFT) methods at the B3LYP/6-311G(d) level. The recent M06-2X functional has also been evaluated but, although the thermodynamic performance is improved, the kinetic data are not necessarily better than those obtained by the popular B3LYP functional for cycloaddition reactions. Four reactive channels associated with the meta and ortho regio- and endo and exo stereoselective appr…

PM3 study of the domino reaction of nitroalkenes with silyl enol ethers

Toward an understanding of the selectivity in domino reactions. A DFT study of the reaction between acetylenedicarboxylic acid and 1, 3-Bis(2-furyl)propane

The mechanism of the domino reaction between acetylenedicarboxylic acid and 1,3-bis(2-furyl)propane has been theoretically studied in the framework of density functional theory. This domino process comprises two consecutive cycloaddition reactions: the first one is initialized by the nucleophilic attack of the C5 position of the furan ring to a conjugate position of acetylenedicarboxylic acid to give a zwitterionic intermediate, which by a subsequent ring-closure process affords an oxanorbornadiene intermediate. The second reaction is an intramolecular concerted cycloaddition of this intermediate to give the final dioxapentacyclic adduct. For the second cycloaddition, which corresponds to t…

Understanding the mechanism of polar Diels–Alder reactions

A good correlation between the activation energy and the polar character of Diels-Alder reactions measured as the charge transfer at the transition state structure has been found. This electronic parameter controls the reaction rate to an even greater extent than other recognized structural features. The proposed polar mechanism, which is characterized by the electrophilic/nucleophilic interactions at the transition state structure, can be easily predicted by analyzing the electrophilicity/nucleophilicity indices defined within the conceptual density functional theory. Due to the significance of the polarity of the reaction, Diels-Alder reactions should be classified as non-polar (N), polar…

Azo-hydrazo conversion via [1,5]-hydrogen shifts. A combined experimental and theoretical study

Abstract Azoalkenes 6e , 6g , 6h , and 8c underwent an easy azo-hydrazo conversion via a [1,5]-hydrogen shift yielding α,β-unsaturated hydrazones. The isomerization products were characterized through spectroscopic and spectrometric techniques. In order to understand the nature of the mechanism of these [1,5]-hydrogen shifts, the transition state structures of the reactions were theoretically studied at the B3LYP/6-31G(d,p) level. Substitution effects in the propenylazo system on the kinetic and thermodynamic parameters were analyzed. An electron localization function (ELF) analysis of the electronic structure of the transition state structure associated with the azo-hydrazo conversion of t…

Ring Expansion versus Cyclization in 4-Oxoazetidine-2- carbaldehydes Catalyzed by Molecular Iodine: Experimental and Theoretical Study in Concert

13 páginas, 3 figuras, 12 esquemas, 2 tablas.-- El documento en word es el articulo post-print.

Unusual Regioselectivity in the Opening of Epoxides by Carboxylic Acid Enediolates

Addition of carboxylic acid dianions appears to be a potential alternative to the use of aluminium enolates for nucleophilic ring opening of epoxides. These conditions require the use of a sub-stoichiometric amount of amine (10% mol) for dianion generation and the previous activation of the epoxide with LiCl. Yields are good, with high regioselectivity, but the use of styrene oxide led, unexpectedly, to a mixture resulting from the attack on both the primary and secondary carbon atoms. Generally, a low diastereoselectivity is seen on attack at the primary center, however only one diastereoisomer was obtained from attack to the secondary carbon of the styrene oxide.

Ab Initio Study of Stereo- and Regioselectivity in the Diels−Alder Reaction between 2-Phenylcyclopentadiene and α-(Methylthio)acrylonitrile

Ab initio molecular orbital calculations have been used to investigate the Diels−Alder reaction between 2-phenylcyclopentadiene and α-(methylthio)acrylonitrile. Geometry optimizations were performed with the RHF/3-21G, RHF/3-21G*, and RHF/6-31G* calculations while the correlation energy has been calculated at MP2 and MP3 levels. Four asynchronous transition structures corresponding to the formation of different stereoisomers and regioisomers associated with the four reaction channels have been located. The observed endo/exo stereoselectivity and para/meta regioselectivity are correctly described at all levels of calculation, and the calculated activation energies reflect accurately the rela…

Conjugate addition of organolithium reagents to α,β-unsaturated carboxylic acids

Abstract Conjugate addition of primary, secondary, tertiary alkyl and phenyl lithium reagents to 2-alkenoic acids affords good yields of branched saturated carboxylic acids. Methyl groups at the α- and β-carbon of the 2-alkenoic acid decrease reactivity as acceptors, and foster deprotonation, respectively. The lithium enediolate resulting from the conjugate addition can react with electrophiles. PM3 calculations are in agreement with the substituent effects.

Designing a Transition State Analogue for the Disfavored Intramolecular Michael Addition of 2-(2-Hydroxyethyl)acrylate Esters

The rate-determining steps for the intramolecular 1,2 and 1,4 addition reactions in basic medium of methyl 2-(2-hydroxyethyl)acrylate to give the corresponding γ-lactone and tetrahydrofuran, respec...

Density functional theory study of the Lewis acid-catalyzed Diels-Alder reaction of nitroalkenes with vinyl ethers using aluminum derivatives

The inverse electron demand Diels–Alder reaction of nitroalkenes with vinyl ethers catalyzed by Lewis acids based on aluminum metal, AlMe3, Al(OMe)3 and AlCl3 was studied using density functional theory methods. A continuum model was selected to represent the effects of dichloromethane used as solvent. For this cycloaddition reaction two reactive channels corresponding to the endo and exo approach modes of the vinyl ether to the Lewis acid-coordinated nitroalkene were studied. Coordination of the aluminum metal to an oxygen atom of the nitroalkene increases the electrophilicity of the heterodiene, decreasing the activation energy of the cycloaddition. The substitution effect on the aluminum…

Unravelling the mechanism of the ketene-imine Staudinger reaction. An ELF quantum topological analysis

The mechanism of the ketene-imine Staudinger (KI-S) reaction between t-butyl-cyano ketene and N-phenyl phenylimine has been studied using DFT methods at the MPWB1K/6-311G(d) computational level. The reaction takes place through a two-step mechanism: (i) the first step is the nucleophilic attack of the imine nitrogen lone pair on the central carbon of the ketene yielding a zwitterionic (ZW) intermediate; (ii) the second step, which is the rate- and stereoselectivity-determining step, is a ring-closure process achieved by a nucleophilic attack of the terminal carbon atom of the ketene on the imine carbon atom. Due to the unfeasibility of a cis/trans and an E/Z stereoisomerisation at the ZW in…

Understanding the domino reactions of alkyne-tethered N-tosylhydrazones yielding fused polycyclic pyrazoles. An MEDT study

Abstract The domino reactions of alkyne-tethered N-mesylhydrazones yielding fused polycyclic pyrazoles have been studied within the Molecular Electron Density Theory (MEDT). Analysis of the Gibbs free energies indicates that the more favourable reactive path is the one in which the elimination of mesylate anion takes place before the intramolecular [3 + 2] cycloaddition (IM32CA) reaction, which corresponds with the rate-determining step of these domino processes. ELF topological analysis of the bond formation along the IM32CA reaction indicates that in spite of the high activation energy associated to this intramolecular reaction, it shows a pmr-type mechanism characterised by the presence …

ChemInform Abstract: A Theoretical Study of the Selectivity for the Domino [5 + 2]/[4 + 2] Cycloadditions of γ-Pyrones Bearing Tethered Alkenes with Substituted 1,3-Butadienes.

Abstract Selectivity of the domino [5+2]/[4+2] cycloaddition reactions of a β-silyloxy-γ-pyrone bearing a tethered alkene with two substituted 1,3-butadienes have been theoretically studied at the B3LYP/6-31G∗//AM1 and B3LYP/6-31G∗ computational levels. Analysis of these results allow explaining the regio, stereo and chemoselectivity observed experimentally at these domino reactions. Selectivity outcome is reproduced by these calculations.

1,3-Dipolar cycloaddition of 1H-pyrazinium-3-olate and N1- and C-methyl substituted pyrazinium-3-olates with methyl acrylate: a density functional theory study

Abstract A DFT study of the 1,3-dipolar cycloaddition of methyl acrylate to 1H-pyrazinium-3-olate and N1- and C-methyl substituted pyrazinium-3-olates, in the gas phase and in THF, has been carried out at the B3LYP/6-31G(d) level. Two stereoisomeric pathways, endo and exo, and two regioisomeric channels, 2-oxo-3,8-diazabicyclo[3.2.1]octane-6-ester and 7-ester products, have been considered. Thermodynamic and kinetic parameters calculated at room temperature have been analyzed. The regioselectivity has been interpreted using reactivity indices. It is generally found that the exo pathway is preferred and the formation of the 6-esters is dominant. The theoretical data obtained for the cycloadd…

Molecular Electron Density Theory Study of Fused Regioselectivity in the Intramolecular [3+2] Cycloaddition Reaction of Cyclic Nitrones

DFT exploration of [3 + 2] cycloaddition reaction of 1H-phosphorinium-3-olate and 1-methylphosphorinium-3-olate with methyl methacrylate

A Molecular Electron Density Theory (MEDT) study of the regio- and stereoselectivity of the [3 + 2] cycloaddition (32CA) reaction of 1H-phosphorinium-3-olate and 1-methylphosphorinium-3-olate with methyl methacrylate was carried out using the B3LYP/6-31G(d) method. In order to test the method dependence for the most favorable reaction path leading to the 1H-substituted 6-exo cycloadduct (CA) various functionals using higher basis sets were taken into consideration in the gas phase. An analysis of the energetic parameters indicates that the reaction path leading to 6-exo CA are kinetically as well as thermodynamically favored in the gas phase, THF and ethanol. The calculated energetic parame…

Understanding the domino reaction between 3-chloroindoles and methyl coumalate yielding carbazoles. A DFT study.

The molecular mechanism of the reaction between N-methyl-3-chloroindole and methyl coumalate yielding carbazole has been studied using DFT methods at the MPWB1K/6-311G(d,p) level in toluene. This reaction is a domino process that comprises three consecutive reactions: (i) a polar Diels-Alder (P-DA) reaction between indole and methyl coumalate yielding two stereoisomeric [2 + 4] cycloadducts (CAs); (ii) the elimination of HCl from these CAs affording two stereoisomeric intermediates; and (iii) the extrusion of CO2 in these intermediates, finally yielding the carbazole. This P-DA reaction proceeds in a completely regioselective and slightly exo selective fashion. In spite of the highly polar …

Toward an Understanding of the Molecular Mechanism of the Reaction between 1-Methylpyrrole and Dimethyl Acetylenedicarboxylate. An ab Initio Study

The molecular mechanism for the reaction between 1-methylpyrrole and dimethyl acetylenedicarboxylate (DMAD) has been studied using ab initio methods. Two alternative reaction pathways have been considered, both of which correspond to stepwise processes with initial, rate-determining formation of a common zwitterionic intermediate. This intermediate is formed by nucleophilic attack of the pyrrole ring to the carbon−carbon triple bond of DMAD. Closure of this intermediate (pathway A) affords a [4 + 2] cycloadduct, whereas intramolecular proton transfer (pathway B) affords a Michael adduct. The much larger potential energy barrier of the second step in pathway B relative to pathway A is respon…

Understanding C C bond formation in polar reactions. An ELF analysis of the Friedel Crafts reaction between indoles and nitroolefins

[EN] The Friedel-Crafts (FC) reaction of N-methyl indole 1 with nitroethylene 2 has been studied using DFT methods at the B3LYP/6-31+G** level in order to characterize the bonding changes along the C-C bond-formation process in polar reactions. For this FC reaction a two-step mechanism has been found. The first step is associated with the C-C bond formation between the most electrophilic centre of nitroethylene and the most nucleophilic centre of N-methyl indole, to yield a zwitterionic intermediate IN. The second step corresponds to an intramolecular proton transfer process at IN, regenerating the aromatic system present at the indole. Despite the high electrophilic character shown by nitr…

A DFT Study of the Domino Inter [4 + 2]/Intra [3 + 2] Cycloaddition Reactions of Nitroalkenes with Enol Ethers

The molecular mechanism of the domino inter [4 + 2]/intra [3 + 2] cycloaddition reactions of nitroalkenes with enol ethers to give nitroso acetal adducts has been characterized using density functional theory methods with the B3LYP functional and the 6-31G* basis set. The presence of Lewis acid catalyst and solvent effects has been taken into account to model the experimental environment. These domino processes comprise two consecutive cycloaddition reactions:  the first one is an intermolecular [4 + 2] cycloaddition of the enol ether to the nitroalkene to give a nitronate intermediate, which then affords the final nitroso acetal adduct through an intramolecular [3 + 2] cycloaddition reacti…

Experimental and theoretical push-pull Chemo- and regioselectivity in 1,3-Dipolar cycloaddition reactions: the case of benzotriazepin-5-one with mesitylnitrile oxide

A novel heterocyclic compound 3-mesityl-5-methyl-4,5,11,11a-tetrahydro-6H-[1,2,4]oxadiazolo [5,4-b][1,3,4]benzotriazepin-6-one 4 has been synthesised by a 1,3 dipolar cycloaddition (13DC) reaction of 1,3,4-benzotriazepin-5-one 1 with mesitylnitrile oxide 3. The reaction, beside its synthetic interest, has shown to be completely chemo- and regioselective. The structure of the compound was determined by X-ray crystallography and analysed by spectral methods (NMR and mass spectrometry). The molecular mechanism for the reaction has been studied using quantum mechanical calculations at the B3LYP/6-31G* theory level. Two mechanisms are possible for the formation of the cycloadduct 4. The first on…

The nucleophilic addition of nitrones to carbonyl compounds: insights on the nature of the mechanism of the l-proline induced asymmetric reaction from a DFT analysis

Abstract The mechanism of the l -proline induced asymmetric nitrone–aldol reaction of N -methyl- C -ethylnitrone with dimethyl ketomalonate has been studied by using density functional theory at B3LYP/6-31G** level. The reaction was initialized by the addition of l -proline to the nitrone to form an aminal, which by elimination of the hydroxylamine gave a chiral enamine. The nucleophilic addition of this chiral enamine to dimethyl ketomalonate corresponds to stereoselective C–C bond-formation step. Further nucleophilic addition of hydroxylamine to the zwitterionic intermediate formed in the enamine addition gave a second aminal, which by l -proline elimination afforded the corresponding β-h…

Unveiling the Lewis Acid Catalyzed Diels–Alder Reactions Through the Molecular Electron Density Theory

The effects of metal-based Lewis acid (LA) catalysts on the reaction rate and regioselectivity in polar Diels&ndash

A Comparative Analysis of the Electrophilicity of Organic Molecules between the Computed IPs and EAs and the HOMO and LUMO energies

[EN] The electrophilicity index, omega, of a series of substituted ethylenes used in some relevant organic reactions has been evaluated from the ionization potential JP) and the electron affinity (EA) computed by vertical ionization at the B3LYP/aug-cc-PVTZ level. The corresponding electrophilicity values are well correlated with those obtained from the HOMO and LUMO energies of the neutral molecules. The good linear correlation found between omega(I,A) and omega(H,L)(LBS), and between omega(H,L)(LBS) and omega(H,L)(SBS) allows to confirm the use of the easily available B3LYP/6-31G(*) HOMO and LUMO energies to obtain reasonable values of the global electrophilicity index of organic molecule…

ChemInform Abstract: Applications of the Conceptual Density Functional Theory Indices to Organic Chemistry Reactivity

Theoretical reactivity indices based on the conceptual Density Functional Theory (DFT) have become a powerful tool for the semiquantitative study of organic reactivity. A large number of reactivity indices have been proposed in the literature. Herein, global quantities like the electronic chemical potential μ, the electrophilicity ω and the nucleophilicity N indices, and local condensed indices like the electrophilic P k + and nucleophilic P k − Parr functions, as the most relevant indices for the study of organic reactivity, are discussed.

Lewis Acid Mediated Domino Reaction between 2-Cyclohexenone and Methyl Azide - A DFT Study

We have studied the Lewis acid mediated domino reaction between 2-cyclohexenone and methyl azide at the B3LYP/6-31G* and B3LYP/6-31+G**//B3LYP/6-31G* levels of theory. A complete survey of the potential energy surface is presented, and the structures of the stationary points and the corresponding molecular mechanism are discussed. The calculations suggest that the product, a cyclopentanone derivative, is formed by means of a domino process that comprises three consecutive reactions. The first and rate-limiting step is a concerted 1,3-dipolar cycloaddition between the Lewis acid coordinated cyclohexenone and methyl azide that yields the corresponding bicyclic 1,2,3-triazoline. The second rea…

A combined experimental and theoretical study of the alkylation of 3,5-dithioxo-[1,2,4]triazepines

The chemo- and regioselective alkylation reactions of 3,5-dithioxo[1,2,4]triazepine 1 in a basic medium with α,ω-dibromoalkanes 2a–c, Br(CH2)nBr (n = 1–3), are studied experimentally and theoretically. These alkylations, which occur at the thioxo sulfur atom in position 5, afford mainly 5-bromomethylthio-2,7-dimethyl- 2,3-dihydro- 4H[1,2,4]triazepin-3-one 3 for n = 1, 6,8-dimethyl-5-thioxo-2,3,4,5-tetrahydro-6H[1,3]thiazolo[4,5-d][1,2,4]triazepine 4 for n = 2 and 7,9-dimethyl-6-thioxo-2,3,4,5,6,7-hexahydro[1,3]thiazino [4,5-d][1,2,4]triazepine 5 for n = 3. Theoretical calculations have been carried out at the B3LYP/6-31G* and B3LYP(benzene)/6-311+G*//B3LYP/6-31G* levels, in order to rationa…

Theoretical studies on cycloaddition reactions

Cycloaddition reactions represent one of the most powerful processes in organic chemistry. The most common types of cycloaddition reactions are the Diels-Alder (DA) and the 1,3-dipolar cycloaddition reactions (1,3-DCs) which lead to five and six membered rings, respectively. In our ongoing efforts to contribute to the understanding of DA and 1,3-DCs; we studied the following using the B3LYP/6-31G(d) level of theory: 1. The 1,3-DCs of the pyridinium-3-olates and pyrazinium-3-olates with methyl acrylate and methyl methacrylate [1,2]. 2. The competitive hetero-DA and 1,3-DCs of methyl glyoxylate oxime and its tautomeric nitrone with cyclopentadiene in the absence and in the presence of BF3 as …

A DFT study of the Diels–Alder reaction between methyl acrolein derivatives and cyclopentadiene. Understanding the effects of Lewis acids catalysts based on sulfur containing boron heterocycles

Abstract The effects of Lewis acid catalysts based on sulfur containing boron heterocycles on the Diels–Alder reactions of two methyl acroleins with cyclopentadiene have been studied using DFT methods. These reactions take place along highly asynchronous concerted processes. While the reaction with crotonaldehyde leads to the expected endo adduct, the reaction with methacrolein leads to exo one in agreement with the experiments. The catalytic effect can be explained through the analysis of the electrophilicity index (ω) of the reagents, and the molecular structure of the corresponding transition structures.

Polar Diels–Alder reactions using electrophilic nitrobenzothiophenes. A combined experimental and DFT study

Abstract The reactions between 2- and 3-nitrobenzothiophenes with three dienes of different nucleophilicity, 1-methoxy-3-trimethylsilyloxy-1,3-butadiene, 1-trimethylsilyloxy-1,3-butadiene and isoprene developed in anhydrous benzene and alternative under microwave irradiation with molecular solvents or in free solvent conditions, respectively, for produce dibenzothiophenes permit to conclude that both nitroheterocycles act as electrophile with the cited dienes. In the cases of the dienes 1-methoxy-3-trimethylsilyloxy-1,3-butadiene and 1-trimethylsilyloxy-1,3-butadiene which posses major nucleophilicity the observed product is the normal cycloaddition one. However when the diene is isoprene t…

Copper(I)-catalysed regioselective synthesis of pyrazolo[5,1-c]-1,2,4-triazoles: A DFT mechanistic study

Abstract Formation of pyrazolo[5,1-c]-1,2,4-triazoles by means of Cu(I)-catalysed [3+2] cycloaddition (32CA) reactions of C,N-cyclic azomethine imines with phenylacetylene, experimentally reported by Katritzky et al. (JOC 2012, 77, 5813), was studied using the density functional theory (DFT) method. Comparison with the uncatalysed 32CA reaction indicates that the Cu(I) catalyst provides new reaction pathways with lower electronic energy barriers in dichloromethane as solvent. The mechanism proposed by Katritzky for the Cu(I) catalysed reaction is compared with that proposed by Sharpless et al. (JACS 127, 2005, 210). The major difference between these two mechanisms lies in the coordination …

Understanding the molecular mechanism of the [3 + 2] cycloaddition reaction of benzonitrile oxide toward electron-richN-vinylpyrrole: a DFT study

The [3 + 2] cycloaddition (32CA) reaction of benzonitrile oxide, BNO 2, with an electron-rich N-vinylpyrrole derivative, NVP 3a, in the presence of dichloromethane, has been theoretically studied using density functional theory (DFT) methods at the B3LYP/6-31G(d) level. This 32CA reaction presents a relatively high activation Gibbs free energy as a result of the low polar character of this zwitterionic-type (zw-type) reaction. Analyses of the calculated relative Gibbs free energies and transition state geometries indicate that the studied 32CA reaction, in excellent agreement with experimental outcomes, takes place in a complete regioselective manner as a consequence of the steric repulsion…

Theoretical Study of the Reaction of Dimethyl Acetylenedicarboxylate with 1-Methyl-2-(1-substituted vinyl)pyrroles

Abstract A theoretical study of the transition structure for the electrophilic attack step of the 1-methyl-2-vinylpyrrole to dimethyl acetylenedicarboxylate is reported with analytical gradients at AM1 and PM3 semi-empirical levels and ab initio at 3-21G level. The geometry, electronic structure, and vector components are qualitatively computer level and model independent The competition of the Michael addition reactions and Diels-Alder reactions of 1-methyl-2-(1-substituted vinyl)pyrroles with dimethyl acetylenedicarboxylate has been studied at the PM3 semi-empirical level.

Understanding the different reactivity of (Z)- and (E)-β-nitrostyrenes in [3+2] cycloaddition reactions. An MEDT study

The experimental reactivity of isomeric (Z)- and (E)-b-nitrostyrenes participating in [3+2] cycloaddition (32CA) reactions has been analysed on the basis of molecular electron density theory (MEDT) at the HF/6-311G(d,p), B3LYP/6-311G(d,p) and uB97X-D/6-311G(d,p) computational levels. It was found that the polar zw-type 32CA reactions with 5,5-dimethylpyrroline-N-oxide proceed via a one-step mechanism, characterised by the attack of the nucleophilic oxygen centre of the nitrone on the electrophilically activated b-position of these nitrostyrenes. This behaviour is completely understood by means of the analysis of the conceptual DFT reactivity indices. These 32CA reactions present low activat…

The triplet excited state of the biocative compound thiabendazole. Characterization and suitability as reporter for cyclodextrin complexation

Fluorescence spectroscopy, laser flash photolysis (LPF), and density functional theory calculations have been performed to characterize the photobehavior of thiabendazole (1). Direct LFP of 1 results in the generation of a transient absorbing at λmax = 570 nm identified as the triplet excited state (31∗). The intersystem crossing quantum yield is 0.91, and the triplet energy is 288 kJ mol−1. The singlet–triplet energy gap is 84 kJ mol−1. The behavior of thiabendazole within CDs results in a marked enhancement of the triplet lifetime, this change is attributed to the mobility restrictions of included 1 imposed by the cyclodextrin cavities.

A theoretical study of the molecular mechanism of the reaction between N,N-dimethylmethyleneammonium cation and cyclopentadiene.

Quantitative characterization of group electrophilicity and nucleophilicity for intramolecular Diels–Alder reactions

In a previous work (L. R. Domingo, M. J. Aurell, P. Perez and R. Contreras, Tetrahedron 2002, 58, 4417) we proposed that the difference in global electrophilicity index be taken as a measure of the polarity at the transition state in intermolecular Diels-Alder reactions. We herein extend this model to deal with intramolecular Diels-Alder (IMDA) processes. The transferability of the empirical reactivity rules established for the intermolecular DA reactions to the IMDA reactions is discussed. The analysis based on group electrophilicity and nucleophilicity in general fails because having two different reactivity patterns within the same molecule hampers a clean classification of electrophilic…

A condensed-to-atom nucleophilicity index. An application to the director effects on the electrophilic aromatic substitutions

Abstract The local nucleophilicity of simple substituted aromatic systems is shown to be described on a quantitative basis by using a condensed-to-atoms nucleophilicity index. This quantity constitutes an extension of the global nucleophilicity descriptor, N introduced for reagents in cycloaddition reactions and other organic molecules [Journal of Organic Chemistry 73 (2008) 4615–4624; Journal of Molecular Structure (THEOCHEM) 865 (2008) 68–72]. The local projection N k is performed on the basis of the normalization condition of the Fukui functions. It is shown that such a simple index provides useful clues about the director effects of the substituents on the electrophilic aromatic substit…

High chemoselectivity of CS dipolarophile in 1,3-dipolar cycloaddition of nitrilimines and 1,2,4-triazepin-5-one derivatives: experimental, theoretical and X-ray study

Substituted 2,7-dimethyl-3-thioxo-3,4,5,6-tetrahydro-2H-[1,2,4]triazepin-5-one reacts as a dipolarophile with several N-aryl-C-ethoxycarbonylnitrilimines, in equimolar quantities, to give, in all cases, two types of products: diethyl 3-(p-aryl)-2-[N′-(p-aryl)-N′-(2′,7′-dimethyl-5′-oxo-5′,6′-dihydro-2H-[1,2,4]triazepin-3′-yl)-hydrazino]-2,3-dihydro[1,3,4]thiadiazole-2,5-dicarboxylate (3a–3c in 20–25% yield) and ethyl 4-(p-aryl)-5-imino-1,4-dihydro[1,3,4]thiadiazole carboxylate (4a–4c in 45–50% yield). When 1:2 stoichiometry was used, the formation of product 3 (50%) was favoured. The reaction is entirely chemo- and regioselective. The structures of the compounds obtained, where aryl stands f…

Unveiling the high reactivity of strained dibenzocyclooctyne in [3 + 2] cycloaddition reactions with diazoalkanes through the molecular electron density theory

Understanding the Electronic Reorganization along the Nonpolar [3+2] Cycloaddition Reactions of Carbonyl Ylides

[EN] The nonpolar [3+2] cycloaddition (32CA) reaction of the carbonyl ylide (CY) 23 with tetramethylethylene (TME) 24 has been studied with DFT methods at the B3LYP/6-31G* level. This cycloaddition reaction, which has a very low activation energy of 4.7 kcal/mol, takes place through a synchronous transition structure. A topological analysis of the ELF along the 32CA reaction provides a new scope of the electronic structure of CY 23 as a pseudodiradical species offering a sound explanation of the high reactivity of this CY in nonpolar reactions. In addition, this analysis points to the nonparticipation of the oxygen lone pairs in the 32CA reaction. This cycloaddition can be seen as a pseudod…

A combined BET and IQA–REG study of the activation energy of non-polar zw-type [3+2] cycloaddition reactions

A combined Bonding Evolution Theory (BET) and Interacting Quantum Atoms-Relative Energy Gradient (IQA-REG) study is carried out on a non-polar zw-type [3+2] cycloaddition (32CA) reaction. BET is the joint use of Catastrophe Theory and the topology of the Electron Localization Function (ELF) to characterise molecular mechanisms, while IQA is a quantum topological energy partitioning method and REG is a method to compute chemical insight at atomistic level, usually in connection with energy. This 32CA reaction involves the simplest nitrone with ethylene and has been studied here at B3LYP/6-311G(d,p) level within the context of Molecular Electron Density Theory (MEDT), which is based on the id…

1,3-Dipolar cycloadditions of electrophilically activated benzonitrile N-oxides. Polar cycloaddition versus oxime formation.

The reactions of electrophilically activated benzonitrile N-oxides (BNOs) toward 3-methylenephthalimidines (MPIs) have been studied using density functional theory (DFT) at the B3LYP/6-31G* level. For these reactions, two different channels allowing the formation of the [3 + 2] cycloadducts and two isomeric (E)- and (Z)-oximes have been characterized. The 1,3-dipolar cycloadditions take place along concerted but highly asynchronous transition states, while formation of the oximes is achieved through a stepwise mechanism involving zwitterionic intermediates. Both reactions are initiated by the nucleophilic attack of the methylene carbon of the MPIs to the carbon atom of the electrophilically…

A molecular electron density theory study of the Grignard reagent‐mediated regioselective direct synthesis of 1,5‐disubstituted‐1,2,3‐triazoles

Quasi-RRHO approximation and DFT study for understanding the mechanism and kinetics of nitration reaction of benzonitrile with nitronium ion

Abstract The nitration reaction of benzonitrile with nitronium cation, NO2+, has been studied within the Molecular Electron Density Theory at the MN15-L/aug-cc-pVTZ level of theory. For this electrophilic aromatic substitution (EAS) reaction, three regioisomeric reaction paths have been studied. Quasi-RRHO approximation was applied to consider the vibrational contribution to entropy and correct the Gibbs free energy profile of the reaction in the solvent phase. Benzonitrile is less nucleophilically activated than benzene due to the presence of the electron-withdrawing CN group the meta position is the more favorable reaction path of this EAS reaction. The analysis of ELF and AIM demonstrate…

A density functional theory study of the chemoselectivity and regioselectivity of the domino cycloaddition reactions of nitroalkenes with substituted alkenes

The chemoselectivity and regioselectivity of the domino intermolecular [4 + 2]/[3 + 2] cycloaddition reactions of nitroalkenes with substituted alkenes, vinyl ethers as electron-rich alkenes and vinyl ketones as electron-poor alkenes, have been studied using density functional theory (DFT) methods with the B3LYP functional and the 6-31G* basis set. These domino processes comprise two consecutive cycloaddition reactions: the first one is an intermolecular [4 + 2] cycloaddition of the vinyl ether to the nitroalkene to give a nitronate intermediate, which then affords the final nitroso acetal adduct through an intermolecular [3 + 2] cycloaddition reaction with the vinyl ketone. The two consecu…

An MEDT study of the carbenoid-type [3 + 2] cycloaddition reactions of nitrile ylides with electron-deficient chiral oxazolidinones.

The molecular mechanism of the carbenoid-type [3 + 2] cycloaddition (32CA) reactions of a nitrile ylide (NY) with a non-chiral and a chiral oxazolidinone has been studied within Molecular Electron Density Theory (MEDT) at the MPWB1K/6-31G(d) computational level. Topological analysis of the Electron Localisation Function (ELF) of the NY shows that it presents a carbenoid structure. The high nucleophilic character of the NY together with the electrophilic character of the non-chiral oxazolidinone favour a polar 32CA reaction with a very low activation energy, the reaction being completely meta/endo selective. A Bonding Evolution Theory (BET) study of the molecular mechanism makes it possible …

Nitropyrroles, Diels-Alder reactions assisted by microwave irradiation and solvent effect. An experimental and theoretical study

The behaviors of N-tosylnitropyrroles acting as electrophilic dienophiles in polar Diels-Alder reactions joint to different dienes of increeased nucleophilicity are analyzed. The reactions were developed under microwave irradiation using toluene or protic ionic liquids (PILs) as solvents and in free solvent conditions. In all the cases explored we observed good yields in short reaction times. For these reactions, the free solvent condition and the use of protic ionic liquids as solvents offer similar results. However, the free solvent conditions favor environmental sustainability. The role of PILs in these polar Diels-Alder reactions has been theoretically studied within the Molecular Elect…

Electronic fluxes during diels-alder reactions involving 1,2-benzoquinones: mechanistic insights from the analysis of electron localization function and catastrophe theory

By means of the joint use of electron localization function (ELF) and Thom's catastrophe theory, a theoretical analysis of the energy profile for the hetero-Diels-Alder reaction of 4-methoxy-1,2-benzoquinone 1 and methoxyethylene 2 has been carried out. The 12 different structural stability domains obtained by the bonding evolution theory have been identified as well as the bifurcation catastrophes (fold and cusp) responsible for the changes in the topology of the system. This analysis permits finding a relationship between the ELF topology and the evolution of the bond breaking/forming processes and electron pair rearrangements through the reaction progress in terms of the different ways o…

Theoretical study of the regio- and stereoselectivity of the intramolecular Povarov reactions yielding 5H-chromeno[2,3-c] acridine derivatives

The intramolecular Povarov (IMP) reactions involved in the synthesis of 5H-chromeno[2,3-c] acridine derivatives [Tetrahedron Lett., 2010, 51, 3071–3074] have been studied using density functional theory (DFT) methods. The studied IMP reaction is a domino process that comprises two consecutive reactions: (i) a BF3 Lewis acid catalysed intramolecular aza-Diels–Alder (IMADA) reaction of an alkene tethered chromene imine (ATCI) giving a formal [4 + 2] cycloadduct, and (ii) a 1,3-hydrogen shift yielding the final chromeno product. The possible regio-(fused/bridged) and stereo-(cis/trans) isomeric channels associated with the IMADA reaction were thoroughly investigated and analysed. The activatio…

Understanding the Bond Formation in Hetero Diels-Alder Reactions. An ELF Analysis of the Reaction of Nitroethylene with Dimethylvinylamine

[EN] The bonding evolution in hetero-Diels-Alder (HDA) reactions has been studied by an ELF analysis of the electron reorganization along the HDA reaction between nitroethylene 6 and dimethylvinylamine (DMVA) 9 at the B3LYP/6-31G* level. This cycloaddition takes place along a two-stages one-step mechanism. In the first stage of the reaction, the C1-C6 bond is formed by coupling of two pseudoradical centers positioned at the most electrophilic carbon of nitroethylene 6 and the most nucleophilic center of DMVA 9. In the second stage, the formation of the second O4-C7 bond takes place between a pseudoradical center positioned at the C7 carbon of DMVA and some electron-density provided by the l…

Are one-step aromatic nucleophilic substitutions of non-activated benzenes concerted processes?

Aromatic nucleophilic substitution (SNAr) reactions of non-electrophilically activated benzenes have been studied within the Molecular Electron Density Theory (MEDT) at the B3LYP/6-311+G(d) computational level. These reactions, taking place through a one-step mechanism, present a high activation Gibbs free energy, ΔG≠ = 31.0 kcal mol-1, which decreases to 22.1 kcal mol-1 in the intramolecular process. A topological analysis of the electron localisation function along the reaction paths permits establishing the non-concerted nature of these SNAr reactions. A series of unstable structures, with similar electronic structures to those of Meisenheimer intermediates, are characterised. The presen…

A further exploration of a nucleophilicity index based on the gas-phase ionization potentials

An empirical nucleophilicity index based on the gas-phase ionization potentials has been recently shown to be useful categorizing and settling the nucleophilicity power of a series of captodative ethylenes reacting in cycloaddition reactions (L.R. Domingo, E. Chamorro, P. Perez, Journal of Organic Chemistry 73 (2008) 4615–4624). In the present work, the applicability of such model is tested within a broader series of substituted alkenes, substituted aromatic compounds and simple nucleophilic molecules. This index obtained within a Koopman’s theorem framework has been evaluated here in both gas and solution phases for several well-known nucleophiles. These results are found to be linearly co…

Closer Investigation of the Kinetics and Mechanism of Spirovinylcyclopropyl Oxindole Reaction with 3Σ–g-O2 by Topological Approaches and Unraveling the Role of the I2 Catalyst

In this investigation at the MN15L/Def2-TZVP level of theory, we present computational evidence indicating that the reaction of 3Σ-g-O2 with spirovinylcyclopropyl oxindole (2) leads to a product called spiro-1,2-dioxolane (2) in its singlet state; this reaction occurs via a stepwise mechanism and its rate-determining step is catalyzed by iodine radicals, which promotes opening of the three-membered ring under dark conditions. The conversion of 2 to 1-benzylindoline-2,3-dione (3) and 2-vinyloxirane (4) takes place via a concerted and slightly asynchronous reaction. Both electron localization function and AIM topological analysis reveal that the step associated with the attack of the 3Σ-g-O2 …

How does the global electron density transfer diminish activation energies in polar cycloaddition reactions? A Molecular Electron Density Theory study

Abstract The key role of the Global Electron Density Transfer (GEDT) in polar cycloaddition reactions is analysed within the Molecular Electron Density Theory (MEDT) using Density Functional Theory (DFT) calculations at the MPWB1K/6-311G(d) computational level. A comparative MEDT study of the non-polar Diels-Alder reaction between cyclopentadiene (Cp) and ethylene and the polar Diels-Alder reaction between Cp and tetracyanoethylene makes it possible to establish that the GEDT taking place in the direction of the transition state structures favours the bonding changes required for the formation of the new C C single bonds along polar cycloaddition reactions. Analysis of the reactivity indice…

Steric interactions controlling the syn diastereofacial selectivity in the [3 + 2] cycloaddition reaction between acetonitrile oxide and 7-oxanorborn-5-en-2-ones: A molecular electron density theory study

A Molecular Electron Density Theory study of the zw-type 32CA reactions of acetonitrile oxide (NO) with two 7-oxanorborn-5-en-2-ones (ONBs) has been performed at the DFT B3LYP/6-31G(d) computational level. These cycloadditions proceed through one-step mechanisms with high activation energies and present low para regio and complete syn diastereofacial selectivities. While the non-polar character of these zw-type 32CA reactions, which is the consequence of the insufficient electrophilic activation of ONBs, according to the analysis of the conceptual DFT reactivity indices, accounts for the high activation energies, and low para regioselectivity, NCI topological analyses at the anti/syn pairs …

Straightforward Regio- and Diastereoselective Synthesis, Molecular Structure, Intermolecular Interactions and Mechanistic Study of Spirooxindole-Engrafted Rhodanine Analogs

Straightforward regio- and diastereoselective synthesis of bi-spirooxindole-engrafted rhodanine analogs 5a–d were achieved by one-pot multicomponent [3 + 2] cycloaddition (32CA) reaction of stabilized azomethine ylide (AYs 3a–d) generated in situ by condensation of L-thioproline and 6-chloro-isatin with (E)-2-(5-(4-chlorobenzylidene)-2,4-dioxothiazolidin-3-yl)-N-(2-morpholinoethyl)acetamide. The bi-spirooxindole-engrafted rhodanine analogs were constructed with excellent diastereo- and regioselectivity along with high chemical yield. X-ray crystallographic investigations for hybrid 5a revealed the presence of four contiguous stereocenters related to C11, C12, C19 and C22 of the spiro struct…

A molecular electron density theory study of the [3 + 2] cycloaddition reaction of nitrones with ketenes.

The [3 + 2] cycloaddition (32CA) reaction between nitrones and ketenes has been studied within the Molecular Electron Density Theory (MEDT) at the Density Functional Theory (DFT) MPWB1K/6-311G(d,p) computational level. Analysis of the conceptual DFT reactivity indices allows the explanation of the reactivity, and the chemo- and regioselectivity experimentally observed. The particular mechanism of this 32CA reaction involving low electrophilic ketenes has been elucidated by using a bonding evolution theory (BET) study. It is determined that this reaction takes place in one kinetic step only but in a non-concerted manner since two stages are clearly identified. Indeed, the formation of the se…

Unveiling the high reactivity of benzyne in the formal [3+2] cycloaddition reactions towards thioamides through the Molecular Electron Density Theory

Abstract The domino reaction of benzyne with thioamide has been studied within the Molecular Electron Density Theory (MEDT) at the MPWB1K/6-311G(d) level. This domino reaction takes place through i) a formal [3 + 2] cycloaddition (32CA) reaction affording an ammonium ylide, and ii) an extrusion of ethylene from this species yielding a dihydrothiazole. Topological analysis of the electron density of benzyne shows its pseudodiradical structure, that is, without any energy cost, changes to a carbenoid one, allowing its participation as electrophile in polar reactions. As a consequence, the formal 32CA reaction does not have an activation enthalpy. Analysis of the changes of electron density al…

Understanding the Origin of the Regioselectivity in Non-polar [3+2] Cycloaddition Reactions through the Molecular Electron Density Theory

The regioselectivity in non-polar [3+2] cycloaddition (32CA) reactions has been studied within the Molecular Electron Density Theory (MEDT) at the B3LYP/6-311G(d,p) level. To this end, the 32CA reactions of nine simplest three-atom-components (TACs) with 2-methylpropene were selected. The electronic structure of the reagents has been characterized through the Electron Localisation Function (ELF) and the Conceptual DFT. The energy profiles of the two regioisomeric reaction paths and ELF topology of the transition state structures are studied to understand the origin of the regioselectivity in these 32CA reactions. This MEDT study permits to conclude that the least electronegative X1 end atom…

[3 + 2] Cycloadditions in Asymmetric Synthesis of Spirooxindole Hybrids Linked to Triazole and Ferrocene Units: X-ray Crystal Structure and MEDT Study of the Reaction Mechanism

Derivatization of spirooxindole having triazole and ferrocene units was achieved by the [3 + 2] cycloaddition (32CA) reaction approach. Reacting the respective azomethine ylide (AY) intermediate generated in situ with the ethylene derivative produced novel asymmetric cycloadducts with four contiguous asymmetric carbons in an overall high chemical yield with excellent regioselectivity and diastereoselectivity. X-Ray single-crystal structure analyses revealed, with no doubt, the success of the synthesis of the target compounds. The 32CA reaction of AY 5b with ferrocene ethylene 1 has been studied within MEDT. This 32CA reaction proceeds via a two-stage one-step mechanism involving a high asyn…

ChemInform Abstract: Conversion of Resin Acids into Steroidal Compounds. A Review

(1991). CONVERSION OF RESIN ACIDS INTO STEROIDAL COMPOUNDS. A REVIEW. Organic Preparations and Procedures International: Vol. 23, No. 3, pp. 321-356.

Lithium Cation-Catalyzed Benzene Diels-Alder Reaction: Insights on the Molecular Mechanism Within the Molecular Electron Density Theory.

The lithium cation Li+-catalyzed Diels-Alder (DA) reactions of benzene toward a series of acetylenes of improved nucleophilicity can be described within the context of the molecular electron density theory (MEDT) at the ωB97XD/6-311G(d,p) level. Conceptual density functional theory indices characterize the crown ether solvated complex benzene-lithium Bz-Li-Cro as a superelectrophile. Coordination of a lithium cation to benzene does not change substantially the electron localization function electronic structure of benzene. The DA reaction of Bz-Li-Cro with acetylene shows a reduction of the energy of activation of 6.9 kcal·mol-1, which is not sufficient for the reaction to take place, thus …

Density Functional Theory Study of the Cycloaddition Reaction of Furan Derivatives with Masked o-Benzoquinones. Does the Furan Act as a Dienophile in the Cycloaddition Reaction?

The molecular mechanism for the cycloaddition reaction between 2-methylfuran and a masked o-benzoquinone has been characterized using quantum mechanical calculations at the B3LYP/6-31G theory level. An analysis of the results on the reaction pathway shows that the reaction takes place along a polar stepwise mechanism. The first and rate-determining step corresponds to the nucleophilic attack of the furan ring on the doubly conjugated position of the 2,4-dienone system present at the masked o-benzoquinone to give a zwitterionic intermediate. Closure of this intermediate affords the formally [2 + 4] cycloadduct. For the second step two reactive channels have been characterized corresponding t…

Understanding the polar mechanism of the ene reaction. A dft study

The molecular mechanism of ene reactions has been characterised by DFT methods at the MPWB1K/6-311G(d,p) level of theory. Most reactions take place along a two-stage one-step mechanism in which the C-C bond formation takes place before the hydrogen transfer process. A very good correlation between the polar character of the reaction measured by the global electron density transfer at the transition state and the activation energy has been found. This behaviour allows establishing a useful classification of ene reactions in N-ene having a very high activation energy, P-ene reactions having activation energies between 35 and 20 kcal mol(-1), and H-ene reactions having activation energies belo…

A combined experimental and theoretical study of the thermal cycloaddition of aryl azides with activated alkenes.

International audience; Reactions were performed from aryl azides on the one hand, and activated alkenes coming from β-dicarbonyl compounds or malonodinitrile on the other hand, either with recourse to conventional heating or to microwave activation, to afford 1-aryl-1H-1,2,3-triazoles. The mechanism and the regioselectivity of the reactions involving β-dicarbonyl compounds have been theoretically studied using DFT methods at the B3LYP/6-31G* level: they are domino processes comprising a tautomeric equilibrium of the β-dicarbonyl compounds with their enol forms, a 1,3-dipolar cycloaddition of the enol forms with the aryl azides (high activation energy), and a dehydration process (lower acti…

Why Do Five-Membered Heterocyclic Compounds Sometimes Not Participate in Polar Diels–Alder Reactions?

The reactions of bicyclic enone (BCE, 1) with cyclopentadiene (Cp, 2) and the five-membered heterocyclic compounds (FHCs) furan 3 and N-methyl pyrrole 4 for the construction of polycyclic heterocyclic compounds have been studied at the B3LYP/6-31G* level. No reaction takes place in the absence of Lewis acid (LA) catalysts as a consequence of the high activation energy associated with these reactions. Electrophilic activation of BCE 1 by formation of a complex with the BF3 LA, 1-BF3, and solvent effects favor the reactions. However, a different reactivity is manifested by Cp 2 and FHCs 3 and 4. Thus, while the reaction of 1-BF3 with Cp 2 yields the expected exo [4 + 2] cycloadduct, the react…

A quantum chemical topological analysis of the c-c bond formation in organic reactions involving cationic species

ELF topological analysis of the ionic Diels-Alder (I-DA) reaction between the N,N-dimethyliminium cation and cyclopentadiene (Cp) has been performed in order to characterise the C-C single bond formation. The C-C bond formation begins in the short range of 2.00-1.96 Åvia a C-to-C pseudoradical coupling between the most electrophilic center of the iminium cation and one of the two most nucleophilic centers of Cp. The electron density of the pseudoradical center generated at the most electrophilic carbon of the iminium cation comes mainly from the global charge transfer which takes place along the reaction. Analysis of the global reactivity indices indicates that the very high electrophilic c…

Unveiling the Unexpected Reactivity of Electrophilic Diazoalkanes in [3+2] Cycloaddition Reactions within Molecular Electron Density Theory

The [3+2] cycloaddition (32CA) reactions of strongly nucleophilic norbornadiene (NBD), with simplest diazoalkane (DAA) and three DAAs of increased electrophilicity, have been studied within the Molecular Electron Density Theory (MEDT) at the MPWB1K/6-311G (d,p) computational level. These pmr-type 32CA reactions follow an asynchronous one-step mechanism with activation enthalpies ranging from 17.7 to 27.9 kcal&middot

General and Theoretical Aspects of the Metal Enolates

1 General Aspects 2 Structure of the Metal Enolates 3 Spectroscopy of the Metal Enolates 4 Reactivity of the Metal Enolates 5 Acknowledgments Keywords: general and theoretical aspects of metal enolates; metal enolate structure; calcium and magnesium enolates; spectroscopy of metal enolates - NMR spectroscopy; UV spectroscopy; enolate, applied to anionic structure with two carbon atoms bound through double bond; IR spectroscopy; generalized gradient approximation (GGA-DFT) for adsorption modes of acetone

DFT study on the cycloreversion of thietane radical cations.

The molecular mechanism of the cycloreversion (CR) of thietane radical cations has been analyzed in detail at the UB3LYP/6-31G* level of theory. Results have shown that the process takes place via a stepwise mechanism leading to alkenes and thiobenzophenone; alternatively, formal [4 + 2] cycloadducts are obtained. Thus, the CR of radical cations 1a, b(center dot+) is initiated by C2-C3 bond breaking, giving common intermediates INa,b. At this stage, two reaction pathways are feasible involving ion molecule complexes IMCa,b (i) or radical cations 4a,b(center dot+) (ii). Calculations support that 1a(center dot+) follows reaction pathway (leading to the formal [4 + 2] cycloadducts 5a). By cont…

Toward an understanding of the unexpected regioselective hetero-Diels-Alder reactions of asymmetric tetrazines with electron-rich ethylenes: a DFT study.

The regioselective hetero-Diels-Alder (HDA) reaction of asymmetric tetrazines (TTZs) with electron-rich (ER) ethylenes has been studied with use of DFT methods at the B3LYP/6-31G* level of theory. The reaction is a domino process that comprises three consecutive reactions: (i) a HDA reaction between the TTZ and the ER ethylene; (ii) a retro-Diels-Alder reaction with loss of nitrogen; and (iii) a beta-hydrogen elimination with formation of the final pyridazines. The first polar HDA reaction, which is associated to the nucleophilic attack of the ER ethylene to the electrophilically activated TTZ, is the rate and regioselectivity determining step of the domino process. The unexpected regiosele…

[pi]-strain-induced electrophilicity in small cycloalkynes: a dft analysis of the polar cycloaddition of cyclopentyne towards enol ethers

Small cycloalkynes possess a π-strain-induced electrophilicity related to the bending of the C–Csp–Csp bond angle. For cyclopentyne and benzyne, the electrophilicity index defined in the context of density functional theory gives a coherent rationale for the reactivity of these cycloalkynes, which may act as electrophiles in polar cycloaddition reactions toward enol ethers. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Experimental and theoretical studies on polar Diels–Alder reactions of 1-nitronaphathalene developed in ionic liquids

The reactions between 1-nitronaphthalene 1 and two nucleophilic dienes, Danishefsky´s diene 2 and 1-trimethylsilyloxy-1,3-butadiene 3, to yield phenanthrenols 7 and 8 developed in protic and aprotic ionic liquids (ILs) with an imidazolium cation base permit to conclude that the reactions occur in better experimental conditions than in molecular solvents. The yields obtained with protic ILs are better than those observed with aprotic ILs. In this sense, the higher yields obtained with aprotic ILs, (working at 60ºC, 48 h) are comparable with the lower yields observed in protic ILs (60 ºC, 24 h). DFT calculations for the reaction of 1-nitronaphthalene 1 with diene 3, in the absence and in the …

A PM3 study of the molecular mechanism for the cycloaddition between cyclopentadiene and protonated pyridine-imine derivatives

Abstract The molecular mechanism of the cycloaddition reaction between cyclopentadiene (CP) and three pyridine-imine derivatives has been studied by means of PM3 semiempirical method. The role of the protonation, endo/exo and π-facial stereoselectivity are analyzed and discussed. In neutral conditions the cycloaddition between CP and the pyridine-imine takes place along a concerted mechanism. Protonation on both nitrogen atoms brings out that the reaction pathway takes with a very low barrier along a stepwise mechanism. PM3 results are capable to find the key factors governing this chemical reaction and to explain the experimental outcome.

Non-classical CH⋯O hydrogen-bond determining the regio- and stereoselectivity in the [3 + 2] cycloaddition reaction of (Z)-C-phenyl-N-methylnitrone with dimethyl 2-benzylidenecyclopropane-1,1-dicarboxylate. A topological electron-density study

The role of the ester groups in the regio- and stereoselectivities of the zw-type [3 + 2] cycloaddition (32CA) reaction of C-phenyl-N-methylnitrone with dimethyl 2-benzylidenecyclopropane-1,1-dicarboxylate (BCPC) has been studied using DFT methods at the MPWB1K/6-31G(d) level. The possible ortho/meta regioisomeric channels and the endo/exo stereoselective approach modes were explored and characterized. Analysis of the relative energies associated with the different reaction pathways indicates that the presence of the two CO2Me groups in the cyclopropane ring has a remarkable effect on selectivities favouring the ortho/endo path, in good agreement with the experimental data. Inclusion of sol…

Invariance of electrophilicity of independent fragments. Application to intramolecular diels-alder reactions

Abstract We herein demonstrate that the global electrophilicity may be distributed into fragments within a single molecule by using an empirical partitioning scheme of the electronic chemical potential framed on the chemical potential inequality principle. Group electrophilicity for several fragments may thereby be defined. Their values show a remarkable stability, independent of the chemical environment they are attached to. The model is applied to asses the chemical reactivity of a series of fragments involved in intramolecular Diels–Alder reactions.

A molecular electron density theory study of the mechanism, chemo- and stereoselectivity of the epoxidation reaction of R -carvone with peracetic acid

The epoxidation reaction of R-carvone 8 with peracetic acid 9 has been studied within the molecular electron density theory at the B3LYP/6-311(d,p) computational level. The chemo- and stereoisomeric reaction paths involving the two C&ndash;C double bonds of R-carvone 8 have been studied. DFT calculations account for the high chemoselectivity involving the C&ndash;C double bond of the isopropenyl group and the low diastereoselectivity, in complete agreement with the experimental outcomes. The Baeyer&ndash;Villiger reaction involving the carbonyl group of R-carvone 8 has also been analysed. A bonding evolution theory analysis of the epoxidation reaction shows the complexity of the bonding cha…

Site-selectivity control in hetero-Diels-Alder reactions of methylidene derivatives of lawsone through modification of the reactive carbonyl group: an experimental and theoretical study.

A new perspective on the reactivity of hydroxyquinones was revealed as an acetal derivative of lawsone was synthesized, isolated, and used in tandem Knoevenagel/hetero-Diels-Alder reactions catalyzed by S-proline. The intermediate alkylidene-1,3-diones that were formed in situ reacted with electron rich alkenes to predominantly afford pyrano-1,2-naphthoquinone (β-lapachone) derivatives along with the isomeric pyrano-1,4-naphthoquinone (α-lapachone) derivatives in high to excellent total yields. Interestingly, the highly reactive arylidene-1,3-dione derivatives were found to be stable and isolable. DFT calculations suggest that these hetero-Diels-Alder reactions have a high polar character, …

A Theoretical Study of the Relationship between the Electrophilicity ω Index and Hammett Constant σp in [3+2] Cycloaddition Reactions of Aryl Azide/Alkyne Derivatives

The relationship between the electrophilicity ω index and the Hammett constant σp has been studied for the [2+3] cycloaddition reactions of a series of para-substituted phenyl azides towards para-substituted phenyl alkynes. The electrophilicity ω index—a reactivity density functional theory (DFT) descriptor evaluated at the ground state of the molecules—shows a good linear relationship with the Hammett substituent constants σp. The theoretical scale of reactivity correctly explains the electrophilic activation/deactivation effects promoted by electron-withdrawing and electron-releasing substituents in both azide and alkyne components.

A DFT study of the molecular mechanisms of the nucleophilic addition of ester-derived lithium enolates and silyl ketene acetals to nitrones: Effects of the lewis acid catalyst

9 pages, 6 schemes, 3 figures, 2 tables.

Mpro-SARS-CoV-2 Inhibitors and Various Chemical Reactivity of 1-Bromo- and 1-Chloro-4-vinylbenzene in [3 + 2] Cycloaddition Reactions

The regioselectvity and the mechanism of the (32CA) cycloadditions reactions of 1-bromo-4-vinylbenzene 1 and 1-chloro-4-vinylbenzene 2 with benzonitrile oxide 3 were investigated under the molecular electron density theory (MEDT) at the B3LYP/6-311++G(d,p) computational level. Evaluation of the ELF reveals that these zwitterionic type (zw-type) 32CA reactions take place in a two-stage one-step mechanism. This MEDT study shows that the meta isoxazolines are kinetically and thermodynamically favored over the ortho ones, these 32CA reactions being completely regioselective, in agreement with experimental outcomes. In addition, the efficiency of isoxazolines against SARS-CoV-2 have been also in…

Theoretical Study of the Gas Phase Decomposition of Glycolic, Lactic, and 2-Hydroxyisobutyric Acids

The reaction mechanism associated with the decomposition of three α-hydroxycarboxylic acids (glycolic, lactic, and 2-hydroxyisobutyric) in the gas phase to form carbon monoxide, water, and the corresponding carbonyl compounds has been theoretically characterized by using ab initio analytical gradients at the MP2 level of theory with the 6-31G** and 6-31++G** basis sets. A detailed characterization of the potential energy surface points out the existence of three competitive reaction pathways for the decomposition process. The first pathway describes a two-step mechanism, with water elimination and formation of an α-lactone intermediate, achieved by the nucleophilic attack of the carbonylic …

The nucleophilicity n index in organic chemistry

The nucleophilicity N index (J. Org. Chem. 2008, 73, 4615), the inverse of the electrophilicity, 1/ω, and the recently proposed inverse of the electrodonating power, 1/ω⁻, (J. Org. Chem. 2010, 75, 4957) have been checked toward (i) a series of single 5-substituted indoles for which rate constants are available, (ii) a series of para-substituted phenols, and for (iii) a series of 2,5-disubstituted bicyclic[2.2.1]hepta-2,5-dienes which display concurrently electrophilic and nucleophilic behaviors. While all considered indices account well for the nucleophilic behavior of organic molecules having a single substitution, the nucleophilicity N index works better for more complex molecules. Unlike…

A theoretical study of the addition of CH3MgCl to chiral α-alkoxy carbonyl compounds

Abstract A theoretical characterisation of the addition of CH 3 MgCl to the carbonyl group of 2-hydroxypropanal and 3,4-di- O -methyl-1- O -trimethylsilyl- l -erythrulose has been carried out. The PM3 semiempirical procedure and the ab initio method at HF level of theory with the 3–21G and 6–31G ∗ basis sets have been applied to identify the stationary points on the potential energy surface. The correlation effects have been included by using the MP2/6–31G ∗ method, as well as by means of MP3/6–31G ∗ // MP2/6–31G ∗ and MP4/6–31G ∗ //MP2/6–31G ∗ single point calculations. The geometry, harmonic vibrational frequencies, transition vector and electronic structure of the transition structures h…

A Combined Experimental and Theoretical Study of the Ammonium Bifluoride Catalyzed Regioselective Synthesis of Quinoxalines and Pyrido[2,3-b]pyrazines

International audience; Ammonium bifluoride was efficiently used (at a 0.5 mol % loading) to catalyze the cyclocondensation between 1,2-arylenediamines and 1,2-dicarbonyl compounds at room temperature in methanol-water, affording quinoxalines and pyrido[2,3-b]pyrazines in excellent yields. Importantly, 2,8-disubstituted quinoxalines and 3-substituted pyrido[2,3-b]pyrazines were regioselectively formed by reacting aryl glyoxals with 3-methyl-1,2-phenylenediamine and 2,3-diaminopyridine, respectively. Analysis of the DFT reactivity indices allowed to explain the catalytic role of ammonium bifluoride.

The mechanism of ionic diels-alder reactions. A dft study of the oxa-povarov reaction

The mechanism of the oxa-Povarov reaction of a cationic aryl oxonium with cyclopentene and styrene has been studied using DFT methods at the B3LYP/6-31G* level as a reaction model of ionic Diels–Alder (I-DA) reactions. Oxa-Povarov reactions are initialized by an I-DA reaction between the cationic aryl oxonium and alkenes to yield the corresponding formal [4+ + 2] cycloadducts. The last step is a rapid loss of a proton giving chromans. While the I-DA reaction with cyclopentene takes place through a two-stage one-step mechanism, the presence of a phenyl substituent on styrene makes the mechanism of the I-DA reaction stepwise. An electron localization function (ELF) bonding analysis of selecte…

A Molecular Electron Density Theory Study of the Reactivity and Selectivities in [3 + 2] Cycloaddition Reactions of C,N-Dialkyl Nitrones with Ethylene Derivatives

The zw-type [3 + 2] cycloaddition (32CA) reactions of C,N-dialkyl nitrones with a series of ethylenes of increased electrophilic character have been studied within the Molecular Electron Density Theory (MEDT) at the MPWB1K/6-311G(d,p) computational level. Both, reactivity and selectivities are rationalized depending on the polar character of the reaction. Due to the strong nucleophilic character of C,N-dialkyl nitrones, the corresponding zw-type 32CA reactions are accelerated with the increased electrophilic character of the ethylene, which also plays a crucial role in the reaction mechanism, thus determining the regio- and stereoselectivities experimentally observed. While, in the 32CA rea…

A DFT study on the NHC catalysed Michael addition of enols to α,β-unsaturated acyl-azoliums. A base catalysed C–C bond-formation step

The NHC catalysed nucleophilic additions of enols to α,β-unsaturated acyl-azolium intermediates have been investigated using DFT methods at the MPWB1K/6-31G** computational level. In the direct and the conjugate additions, formation of a hydrogen bond (HB) with the carboxyl oxygen is not sufficient to favour the C-C bond formation as a consequence of the low nucleophilic character of enols. Interestingly, when enols form a HB with the chloride counterion, the activation energies associated with the conjugate addition decrease as a consequence of the increased nucleophilic character of enols and the increased electrophilic character of the 'acyl-azolium + Cl' ion pair. Analysis of the DFT re…

The Mysticism of Pericyclic Reactions: A Contemporary Rationalisation of Organic Reactivity Based on Electron Density Analysis

Theoretical Studies on the Mechanism of the Formation of Cyclopentadienes and Dihydropyridazines

A DFT study of the ionic [2+2] cycloaddition reactions of keteniminium cations with terminal acetylenes

Abstract The molecular mechanism of the ionic [2+2] cycloaddition (I-22CA) reactions of a keteniminium cation (KC) with acetylene and propyne has been investigated using DFT methods at the MPWB1K/6-311G(d,p) level. These I-22CA reactions take place via a two-step mechanism. The first step is the nucleophilic attack of these alkynes on the central carbon of KC, yielding cyclopropene intermediates, while the second step corresponds to the conversion of these intermediates into more stable cyclobuteniminium cations (CCs). The first step is the rate-determining step, while the second step is responsible for the formation of the two regioisomeric CCs experimentally observed in the reaction with …

On the Catalytic Effect of Water in the Intramolecular Diels–Alder Reaction of Quinone Systems: A Theoretical Study

The mechanism of the intramolecular Diels#8211;Alder (IMDA) reaction of benzoquinone 1, in the absence and in the presence of three water molecules, 1w, has been studied by means of density functional theory (DFT) methods, using the M05-2X and B3LYP functionals for exploration of the potential energy surface (PES). The energy and geometrical results obtained are complemented with a population analysis using the NBO method, and an analysis based on the global, local and group electrophilicity and nucleophilicity indices. Both implicit and explicit solvation emphasize the increase of the polarity of the reaction and the reduction of activation free energies associated with the transition stat…

Understanding the Participation of Fluorinated Azomethine Ylides in Carbenoid-Type [3 + 2] Cycloaddition Reactions with Ynal Systems: A Molecular Electron Density Theory Study

The carbenoid-type (cb-type) 32CA reaction of 1,1-difluoroated azomethine ylide (DFAY) with phenylpropynal has been studied using the molecular electron density theory (MEDT). Electron localization function (ELF) characterizes DFAY as a carbenoid species participating in cb-type 32CA reactions. The supernucleophilic character of DFAY and the strong electrophilic character of the ynal cause this polar 32CA reaction to have an unappreciable barrier; the reaction, which is highly exothermic, presents total chemo- and regioselectivity. ELF topological analysis of the bonding changes along the reaction establishes its non-concerted two-stage one-step mechanism, in which the nucleophilic attack o…

On the nature of organic electron density transfer complexes within molecular electron density theory.

The structural features of a series of organic molecular complexes formed between the strong electrophilic tetracyanoethylene and twelve benzene derivatives with increased nucleophilic character, herein called Electron Density Transfer Complexes (EDTCs), have been studied using Molecular Electron Density Theory. The favourable nucleophilic/electrophilic interactions, which favour the global electron density transfer (GEDT) towards the electrophile, are responsible for the formation of these species. Molecular complexes presenting a GEDT above 0.05e are classified as EDTCs. Analysis of the Parr functions of the separated reagents and the topological analysis of the electron density of the ED…

Unravelling the Mysteries of the [3+2] Cycloaddition Reactions

Controlled rearrangement of lactam-tethered allenols with brominating reagents: a combined experimental and theoretical study on α- versus β-keto lactam formation.

N-Bromosuccinimide (NBS) smoothly promotes the ring expansion of lactam-tethered allenols to efficiently afford cyclic α- or β-ketoamides with good yields and high chemo-, regio-, and diastereoselectivity, through controlled C-C bond cleavage of the β- or γ-lactam nucleus. Interestingly, in contrast to the rearrangement reactions of 2-azetidinone-tethered allenols, which lead to the corresponding tetramic acid derivatives (β-keto lactam adducts) as the sole products, the reactions of 2-indolinone-tethered allenols under similar conditions give quinoline-2,3-diones (α-keto lactam adducts) as the exclusive or major products. To rationalize the experimental observations, theoretical studies ha…

13C nuclear magnetic resonance spectra of several podocarpane and cassane diterpenoids

The 13C NMR spectra of several diterpenic derivatives having the podocarpane and cassane skeleton were recorded and interpreted. The most significant effects due to substituent orientation, B/C ring junction stereochemistry and conformational changes are briefly discussed.

A Close Look to the Oxaphosphetane Formation along the Wittig Reaction: A [2+2] Cycloaddition?

The Wittig reaction between triphenylphosphine methylide and benzaldehyde has been studied both from conceptual and computational approaches. The supernucleophilic character of ylide accounts for the feasibility of the initial nucleophilic attack. The nature of bonding driving the formation of the first oxaphosphetane (OPA) intermediate in such a domino reaction is examined within a topological-based bonding evolution theory perspective. The sequence of the electronic flow associated to the changes in electron density supports a rationalization via two main electronic stages characterizing the single kinetic step: first, the C-C bond formation, which takes place via donation of electron den…

A molecular electron density theory study for [3 + 2] cycloaddition reactions of 1‐pyrroline ‐1‐oxide with disubstituted acetylenes leading to bicyclic 4‐isoxazolines

Stereoselective 1,3-Dipolar Cycloadditions of a Chiral Nitrone Derived from Erythrulose. An Experimental and DFT Theoretical Study

We have investigated several 1,3-dipolar cycloadditions of a chiral nitrone prepared from L-erythrulose. While cycloadditions to carbon-carbon multiple bonds of dipolarophiles such as ethyl acrylate, ethyl propiolate, or dimethyl acetylenedicarboxylate were poorly stereoselective, reaction with acrylonitrile provided predominantly one diastereomeric adduct. Furthermore, the regioselectivity exhibited by the two structurally similar dipolarophiles ethyl acrylate and ethyl propiolate was found to be opposite. The molecular mechanisms of these cycloadditions have thus been investigated by means of density functional theory (DFT) methods with the B3LYP functional and the 6-31G and 6-31+G basis …

A computational and conceptual DFT study on the mechanism of hydrogen activation by novel frustrated Lewis pairs.

A computational and conceptual density functional theory (DFT) study on the mechanism of molecular hydrogen activation by a set of three frustrated Lewis pairs (FLPs) was performed at the ωB97X-D/6-311G(d,p) level of theory. A reduced model and other two prototypes derived from experimental data, based on the donor nitrogen and acceptor boron atoms, were used. Analysis based on the energy results, geometries and the global electron density transfer at the TSs made it possible to obtain some interesting conclusions: (i) despite the well-known very low reactivity of molecular hydrogen, the catalytic effectiveness of the three FLPs produces reactions with almost unappreciable activation energi…

An analysis of the regioselectivity of 1,3-dipolar cycloaddition reactions of benzonitrile n-oxides based on global and local electrophilicity and nucleophilicity indices

The regioselectivity of the 1,3-dipolar cycloaddition (13DC) reactions of benzonitrile N-oxides (BNOs) with electrophilic and nucleophilic alkenes has been analyzed by using global and local nucleophilicity and electrophilicity reactivity indices defined within the conceptual DFT. The BNOs react with electron-deficient and electron-rich ethylenes, but the regioselectivities of these polar reactions are different. Whereas the reactions with electron-rich ethylenes are completely regioselective, yielding 5-isoxazolines, a change in the regioselectivity is observed in the reactions with electron-deficient ethylenes, which yield a mixture of 4- and 5-isoxazolines. Analysis of the energies, geom…

The catalytic effects of a thiazolium salt in the oxa-Diels–Alder reaction between benzaldehyde and Danishefsky's diene: a molecular electron density theory study

The oxa-Diels–Alder (ODA) reaction of benzaldehyde with Danishefsky's diene in the presence of a [thiazolium][Cl] salt, as a model of an ionic liquid, has been studied within Molecular Electron Density Theory (MEDT) at the M06-2X/6-311G(d,p) computational level. The formation of two hydrogen bonds (HBs) between the thiazolium cation and the carbonyl oxygen of benzaldehyde modifies neither the electrophilic character of benzaldehyde nor its electronic structure substantially but accelerates the reaction considerably. This ODA reaction presents an activation energy of 4.5 kcal mol−1; the formation of the only observed dihydropyranone is strongly exothermic by −28.8 kcal mol−1. The presence of…

Toward an Understanding of Molecular Mechanism of Domino Cycloadditions. Density Functional Theory Study of the Reaction between Hexafluorobut-2-yne and N,N‘-Dipyrrolylmethane

Lewis Acid Induced [2+2] Cycloadditions of Silyl Enol Ethers with α,β-Unsaturated Esters: A DFT Analysis

The Lewis acid (LA) induced cycloaddition of trimethysilyl vinyl ether with methyl acrylate has been studied by DFT methods at the B3LYP/6-31G* level. In the absence of an LA, a [4+2] cycloaddition between the silyl enol ether and methyl acrylate in the s-cis conformation takes place through an asynchronous, concerted bond-formation process. This cycloaddition presents a large activation enthalpy of 21.1 kcal mol–1. Coordination of the LA AlCl3 to the carbonyl oxygen atom of methyl acrylate yields a change of molecular mechanism from a concerted to a two-step mechanism and produces a drastic reduction of the activation energy. This stepwise mechanism is initialized by the nucleophilic attac…

A DFT Characterization of the Mechanism for the Cycloaddition Reaction between 2-Methylfuran and Acetylenedicarboxylic Acid

The molecular mechanism for the cycloaddition reaction between 2-methylfuran and acetylenedicarboxylic acid (ADA) has been characterized using density functional theory methods at the B3LYP/6-31+G* theory level. An analysis of the results on the reaction pathway shows that the reaction takes place along a stepwise mechanism. The initial step corresponds to the nucleophilic attack of the C5 position of the furan ring to one carbon atom of the conjugated acetylenic system of ADA to give a zwitterionic intermediate. Closure of this intermediate along the nucleophilic attack of the other acetylenic carbon to the substituted C2 position of the furan ring affords the Diels−Alder cycloadduct. Alth…

A DFT Study of the [3+2] Cycloadditions of RCNO (R = H, Me and F) With Carbon Flatland Mimicking Graphene

Graphene is the latest allotrope of carbon to be under the spotlight ever since its discovery by Novoselov and coworkers in 2004. Owing to its fascinating structural, electrical, optical, mechanical and thermal properties, graphene can be regarded as as a rapidly rising star in various fields such as supercapacitors, biosensors and batteries. The organic chemistry of graphene has stimulated a great deal of research and is gaining considerable attention. Among the various experimental studies which have been carried out on graphene, it is found that [3+2] cycloadditions (32CA) can also be achieved on graphene sheets and the resulting functionalized graphenes are dispersible in polar organic …

A bibracchial lariat aza-crown ether as an abiotic catalyst of malonic acid enolization

A bibracchial lariat aza-crown ether (L) consisting of 2-aminoethylnaphthyl moieties appended to a 2 : 2 azapyridinophane structure displays significant activation of H–D exchange in malonic acid. The compound forms very stable adducts with malonate anions (MA) in the 2–10 pH range. Molecular dynamics studies performed for the species resulting from the interaction of the hexaprotonated macrocycle and the dianion show that malonate is encapsulated by L with distances between the CH2 group of malonate and the pyridine nitrogens of ca. 3.5 A. The pendant arms of L cap above and below the anion, defining a pseudo-cage structure. Quantum chemical calculations for α-proton abstraction from malon…

Understanding the Nature of the Molecular Mechanisms Associated with the Competitive Lewis Acid Catalyzed[4+2] and[4+3] Cycloadditions between Arylidenoxazolone Systems and Cyclopentadiene: A DFT Analysis

The molecular mechanisms of the reactions between aryliden-5(4H)-oxazolone 1, and cyclopentadiene (Cp), in presence of Lewis acid (LA) catalyst to obtain the corresponding [4+2] and [4+3] cycloadducts are examined through density functional theory (DFT) calculations at the B3LYP/6-31G* level. The activation effect of LA catalyst can be reached by two ways, that is, interaction of LA either with carbonyl or carboxyl oxygen atoms of 1 to render [4+2] or [4+3] cycloadducts. The endo and exo [4+2] cycloadducts are formed through a highly asynchronous concerted mechanism associated to a Michael-type addition of Cp to the beta-conjugated position of alpha,beta-unsaturated carbonyl framework of 1.…

Novel examples of the N-methyl effect on cyclisations of N-Boc derivatives of amino alcohols. A theoretical study

New examples of the N-methyl effect on the cyclisation of N-tert-butoxycarbonyl derivatives of amino alcohols are reported. Ab initio studies for the displacement step with formation of the five-membered heterocycle indicate that the increase of the nucleophile character of the carbonyl oxygen of the carbamate group with the N-methyl substitution is responsible for the acceleration of the cyclisation step.

Theoretical Study of the 1,3-Dipolar Cycloaddition Reactions of Azomethine Ylides. A DFT Study of Reaction between Trifluoromethyl Thiomethyl Azomethine Ylide and Acronitrile

The molecular mechanism for the 1,3-dipolar cycloaddition of trifluoromethyl thiomethyl azomethine ylide with acronitrile has been characterized using density functional theory methods with the B3L...

Efficient Synthesis of 5-Chalcogenyl-1,3-oxazin-2-ones by Chalcogen-Mediated Yne-Carbamate Cyclisation: An Experimental and Theoretical Study

A very efficient synthesis of 5-chalcogenyl-1,3-oxazin-2-ones has been accomplished by the chalcogen-mediated yne–carbamate cyclisation of chiral, non-racemic N-Cbz-protected propargylic amines using PhXY (X = Se, S, Te; Y = Br or Cl) as electrophile sources. The reactions gave good-to-excellent yields for a wide range of substrates. In all cases the reaction was totally regioselective, occurring by a 6-endo-dig process regardless of the nature of the reagent and of the substituents in the starting material. This methodology permits the formation of the 1,3-oxazin-2-one moiety as well as the simultaneous installation of a chalcogen functionality onto the heterocyclic ring. The experimental …

Understanding the stereoselectivity in Brønsted acid catalysed Povarov reactions generating cis/trans CF3-substituted tetrahydroquinolines: a DFT study

The Bronsted acid (BA) catalysed Povarov reactions of (E)-1-phenyl-N-(4-(trifluoromethyl)phenyl) methanimine with 1-vinylpyrrolidin-2-one (VPO) and with allyltrimethylsilane (ATMS), affording CF3-substituted cis/trans tetrahydroquinoline (THQ) derivatives, have theoretically been studied using the M06-2X functional together with the standard 6-31G(d) basis set. These BA catalysed Povarov reactions are multistep processes initialised by the nucleophilic attack of the non-substituted carbon atom of the nucleophilic ethylene on the imine carbon atom of the super-electrophilic protonated imine, yielding the corresponding cationic intermediate along the endo/exo stereoisomeric approach mode. Upo…

New highly asymmetric Henry reaction catalyzed by Cu(II) and a C(1)-symmetric aminopyridine ligand, and its application to the synthesis of miconazole.

A new catalytic asymmetric Henry reaction has been developed that uses a C(1)-symmetric chiral aminopyridine ligand derived from camphor and picolylamine. A variety of aromatic, heteroaromatic, aliphatic, and unsaturated aldehydes react with nitromethane and other nitroalkanes in the presence of DIPEA (1.0 equiv), Cu(OAc)(2)*H(2)O (5 mol %), and an aminopyridine ligand (5 mol %) to give the expected products in high yields (up to 99 %), moderate-to-good diastereoselectivites (up to 82:18), and excellent enantioselectivities (up to 98 %). The reaction is air-tolerant and has been used in the synthesis of the antifungal agent miconazole.

A theoretical study on the decomposition mechanism of β-propiolactone and β-butyrolactone

Abstract The reaction mechanism associated with the decomposition of β-propiolactone and β-butyrolactone in the gas phase to form carbon dioxide and ethylene or propene, respectively, has been theoretically characterized by using analytical gradients at the B3LYP/6-31G**, B3LYP/6-31++G**, MP2/6-31G** and MP2/6-31++G** calculation levels, as well as by single point calculations at QCISD(T)/6-31++G**//MP2/6-31++G**. A detailed analysis of the results points out that the reaction pathway can be described as an asynchronous concerted process. The geometrical parameters and the components of the transition vector are weakly dependent on the computational method. By applying transition state theo…

Understanding the mechanism of the N-heterocyclic carbene-catalyzed ring-expansion of 4-formyl-β-lactams to succinimide derivatives

The mechanism of the N-heterocyclic carbene (NHC)-catalyzed ring-expansion of 4-formyl-β-lactams to succinimides has been studied using DFT methods at the B3LYP/6-31G∗∗ level. The first step is the nucleophilic attack of NHC to the aldehyde to yield the zwitterionic intermediate, which by a proton-transfer process affords the Breslow intermediate. The lactam N–C breaking bond in this intermediate yields an enol-amidate, which by a keto–enol type equilibrium becomes the ketone form. The subsequent ring-closure achieved by the nucleophilic attack of the amidate to carbonyl carbon allows the formation of the five-membered ring. Finally, elimination of NHC affords the succinimide. Analysis of t…

CCDC 688220: Experimental Crystal Structure Determination

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CCDC 1013100: Experimental Crystal Structure Determination

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CCDC 941482: Experimental Crystal Structure Determination

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Understanding the [2n+2n] reaction mechanism between a carbenoid intermediate and CO2

The mechanism of the cycloaddition reaction of CO2 with a nucleophilic carbenoid intermediate has been theoretically studied by using the bonding evolution theory (BET) at the B3LYP/6-31G(d) level of theory. BET combines topological analysis of the electron localisation function and catastrophe theory along a reaction path. This cycloaddition reaction is characterised by 16 structural stability domains, associated to the following sequence of catastrophes: C8H9NO4 + CO2: 16-CF†CF†F†CFF†C†C†[FF†]F†FCC†-0: C9H9NO6. Formation of the two new C-C and C-O single bonds evolves after the transition state structure is reached. The high nucleophilic character and the electronic structure of carbenoid…

CCDC 941483: Experimental Crystal Structure Determination

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CCDC 688217: Experimental Crystal Structure Determination

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