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.

Stereocontrolled synthesis of azeto[2,1-b] quinazolines bearing three stereocenters via the intramolecular [2+2] cycloaddition between ketenimines and imines

Abstract A highly stereoselective synthesis of azeto[2,1- b ]quinazolines bearing three stereocenters (C1, C2, and C8) has been achieved via intramolecular [2+2] cycloaddition between ketenimine and imine functions supported on an ortho -benzylic scaffold. An asymmetric center adjacent to the iminic nitrogen atom, the future C8 carbon of the bicyclic product, efficiently controls the absolute configuration of the two new stereogenic carbon atoms of the azetidine ring, C1 and C2.

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.

Crown ethers derived from cyclohexane. Influence of their stereochemistry in complexation and transport

Abstract Crown ethers derived from cyclohexane have been prepared. The trans stereochemistry of the substituents on the carbocyclic ring makes that only one conformation can complex cations. The influence of the stereochemistry in complexation has been studied.

Mercurated and Palladated Iminophosphoranes. Synthesis and Reactivity

Reaction of the iminophosphorane Ph3PNC6H4Me-4 (1a) with Hg(OAc)2 and LiCl gives the mercurated iminophosphorane [Hg{C6H3(NPPh3)-2-Me-5}Cl] (2). The latter reacts with NaBr to give [Hg{C6H3(NPPh3)-2-Me-5}Br] (3). 2 reacts with MeC6H4NCO-4 or CX2 (X = O, S) to give [Hg{C6H3(NCNC6H4Me-4‘)-2-Me-5}Cl] (4) or [Hg{C6H3{NCNC6H3(HgCl)-1‘-Me-5‘}-2-Me-5}Cl] (5), respectively. Iminophosphoranes Ph3PNC6H4R-4 (1b) react with Pd(OAc)2 to give the complexes [Pd{κ2-C,N-C6H4(PPh2NC6H4R-4‘)-2}(μ-OAc)]2 (R = Me (6a), MeO (6b)), in which the palladation takes place at one of the phenyl substituents of the PPh3 group. Complex 6b reacts with NaBr or tBuNC to give [Pd{κ2-C,N-C6H4(PPh2NC6H4OMe-4‘)-2}(μ-Br)]2 (7) o…

ChemInform Abstract: Enantioselective Syntheses of Dopaminergic (R)- and (S)-Benzyltetrahydroisoquinolines.

Optically pure (1S,R)- and (1R,S)-benzyltetrahydroisoquinolines (BTHIQs), 12a,b as the major diastereomers, were prepared by stereoselective reduction of the isoquinolinium salt possessing (R)- and (S)-phenylglycinol as the chiral auxiliary, respectively. The absolute configurations of (1S,R)-13a hydrochloride (O-debenzoylated derivative from 12a) and (1R,S)-12b diastereomers were unambiguously determined by single-crystal X-ray analysis. Reductive removal of the chiral auxiliary group, subsequent N-propylation, and cleavage of the methylenedioxy group furnished the optically active catecholamines (1S)-16a and (1R)-16b in good overall yield. We have separately prepared for the first time pa…

ChemInform Abstract: New Strategy for the Stereoselective Synthesis of Fluorinated β-Amino Acids.

Racemic and chiral nonracemic α-substituted and α-unsubstituted β-fluoroalkyl β-amino acid derivatives 6 and 9 have been synthesized in two steps starting from fluorinated imidoyl chlorides 1 and ester enolates. This approach is based on the chemical reduction of previously obtained γ-fluorinated β-enamino esters 4 by using ZnI2/NaBH4 in a nonchelated aprotic medium (dry CH2Cl2) as the reducing agent. A metal-chelated six-membered model has been suggested to explain the stereochemical outcome of the reduction reaction. The process takes place with high yields and with moderate to good diastereoselectivity. The best results related to diastereoselective reduction of chiral β-enamino esters 4…

Reactivity of the di-μ-hydroxo-complexes [{Pd(NN)}2(μ-OH)2][ClO4]2 (NN=bis(pyrazol-1-yl)alkanes) towards protic electrophiles. Hydration of coordinated nitriles at a palladium(II) site

Abstract The hydroxo-complexes [{Pd(μ-OH)(NN)}2][ClO4]2 (NN=bpzm:bis(pyrazol-1-yl) methane: a-compounds, bpzm*:bis(3,5-dimethylpyrazol-1-yl)methane; b-compounds) react with a wide variety of weak protic electrophiles H(LL) in a 1:2 molar ratio to give the mononuclear cationic palladium(II) derivatives of general formula [Pd(LL)(NN)][ClO4] [LL=2-pyridine-methoxo (OCH2-py) (1a,b); picolinate (pic) (2a,b); 8-hydroxiquinolinate (oxin) (3a,b)] or the dinuclear complexes [{Pd(NN)}2(μ-ox)][ClO4]2 [ox=oxalate: (4a,b)] and [{Pd(μ-LL)(NN)}2][ClO4]2 [LL=pyrazolate (pz) (5a,b); p-thiocresolate (SC6H4Me-p) (6a,b); triazolate (tz) (7b); thiophenolate (SPh) (8b)] when reacting with oxalic acid, azole…

Efficient synthesis and structural analysis of new dioxopiperazine isoquinolines

Abstract We report herein the synthesis of new dioxopiperazine isoquinolines using the Pictet–Spengler cyclisation. Our synthetic strategy for the preparation of two new compounds ( 5 , 6 ), with a tetrahydro-6H-pyrazino[1,2-b]isoquinoline-1,4-dione moiety was developed in only four steps. To understand better the crucial step of the synthesis reported here, theoretical calculations using semiempirical (PM3), ab initio and DFT computations were carried out on a reduced system model. The structure of chlorohydrate water solvate of tetrahydro (2-piperidinylethyl)-6H-pyrazino [1,2-b]isoquinoline-1,4-dione ( 6·HCl·2H2O ) was determined by X-ray diffraction. Theoretical calculations (RHF/3-21G a…

Mono- and di-nuclear complexes of ortho-palladated and -platinated 4,4′-dimethylazobenzene with bis(diphenylphosphino)methane. More data on transphobia

Abstract Complexes [Pd(κ2-R)(μ-Cl)]2 [κ2-R=κ2-C,N′-C6H3(NNC6H4Me-4′)-2-Me-5 (1)] and [Pd(κ1-R)Cl(κ1-dppm)(κ2-dppm)]TfO [dppm=bis(diphenylphosphino)methane (2)] have been used to prepare new palladium derivatives containing dppm. Thus, complex 1 reacts with one equivalent of dppm to afford [{Pd(κ2-R)Cl}2(μ-dppm)] (3) and with AgClO4 and dppm (1:2:2 molar ratios) to give [Pd(κ2-R)(κ2-dppm)]ClO4 (4·ClO4). The triflate salt of this complex (4·TfO) reacts with PPh3 to yield [Pd(κ1-R)(PPh3)(κ2-dppm)]TfO (5). Dinuclear complexes were obtained by reacting 2, (i) with [AuCl(PPh3)] or [AuCl(tht)] (tht=tetrahydrothiophene) (1:1, −60 °C) and (ii) with 1 (2:1) to give, respectively, [Pd(κ1-R)Cl(μ-dppm…

New Carbenegold(I) Complexes Synthesized by the “Acac Method”

The reaction of [AuCl{C(NEt2)NHtBu}] with Tl(acac)] (1:1) gives [Au(C-acac){C(NEt2)NHtBu}] (1). Complex 1 reacts with 2-pyridinethiol (HSpy-2), C6H4(C⋮CH)2−1,3 (2:1), [Ph3PCH2CO2Me]ClO4, [Me3S(O)]ClO4, or [Me3NH]ClO4 to give, respectively, [Au(Spy-2){C(NEt2)NHtBu}] (2), [{AuC(NEt2)NHtBu}2(μ−C⋮CC6H4C⋮C-3)] (3), [Au{C(NEt2)NHtBu}{CH(PPh3)CO2Me}]ClO4 (4), [Au{C(NEt2)NHtBu}{CH2S(O)Me2}]ClO4 (5), or [Au{C(NEt2)NHtBu}(NMe3)]ClO4 (6). The crystal structures of 1, 3, and 5 have been determined.

New Di- and Trinuclear Complexes with Pyrazolato Bridges. Crystal Structures of [{(C6F5)2Pd(μ-pz)(μ-Cl)}2Pd]2– and [(C6F5)2Pd(μ-pz)2Pd(η3-C4H7)] (pz = pyrazolate)

Synthesis and Reactivity toward Isonitriles of (2-Aminoaryl)palladium(II) Complexes

Mixtures of “Pd(dba)2” (dba = dibenzylideneacetone) and 2,2‘-bipyridine (bpy; 1:2) or N,N,N‘,N‘-tetramethylethylenediamine (tmeda; 1:1) react with 2-bromo-4-nitroaniline to give [Pd{C6H3NH2-2-NO2-5}Br(N−N)] (N−N = bpy (1b), tmeda (1b‘)). Reactions of 2-iodoaniline with mixtures of “Pd(dba)2” and isonitriles RNC (R = C6H3Me2-2,6 (Xy), 2:1:2 molar ratios; R = tBu, 2.9:1:2 molar ratios) result in the formation of the complexes [Pd{κ2C,N-C(NXy)C6H4NH2-2}I(CNXy)] (2a) and trans-[Pd{C(NtBu)C6H4NH2-2}I(CNtBu)2] (3a*). The reactions of [Pd{C6H4NH2-2}I(bpy)] and 1b‘ with RNC give the complexes trans-[Pd{C(NR)C6H3NH2-2-Y-5}}X(CNR)2] (Y = H, X = I, R = Xy (3a), tBu (3a*); Y = NO2, X = Br, R = Xy (3b),…

Syntheses of dopaminergic 1-cyclohexylmethyl-7,8-dioxygenated tetrahydroisoquinolines by selective heterogeneous tandem hydrogenation

Abstract We describe the preparation in a ‘one-pot’ sequence 1-cyclohexylmethyl 7,8-dioxygenated tetrahydroisoquinoline, substituted and unsubstituted in the C ring by application of the Photo–Fries transposition, followed by a tandem reduction–cyclization and further reduction. Indeed, we have accomplished for the first time regioselective hydrogenation of the benzylic ring of the tetrahydroisoquinoline systems. All 1-cyclohexylmethyl THIQ synthesized were able to displace D2 dopamine receptor from its specific binding site in rat striatal membranes, while the N-methylated derivatives showed also affinity for D1 dopamine receptors.

Polyazapodands Derived from Biphenyl. Study of their Behaviour as Conformationally Regulated Fluorescent Sensors

Eight new polyazapodands containing a 4,4′-substituted biphenyl moiety have been synthesised. Four (7, 8, 9 and 11) are functionalised on positions 4 and 4′ with a nitro group and four (1, 2, 3 and 10) with a dimethylamino substituent. Comparison of the emission behaviour of 1, 2, 3 with that of the reference compounds 10 and tetramthylbenzidine, clearly suggests that a modification in the dihedral angle between the biphenyl rings is an important factor in determining the fluorescent response of the molecule. The fluorescence is pH dependent, due to the formation of intramolecular hydrogen bonds between protonated aliphatic nitrogens and a carbonyl oxygen, which influences the aforementione…

Synthesis of a New pH-Dependent Ligand: Conformational and Complexation Studies

A new macrocyclic ligand, 3, which exhibits pH-induced conformational changes, has been prepared. This ligand consists of a crown ether derived from a trans-anti-trans 1,2,4,5-tetrasubstituted cyclohexane. Due to the stereochemistry of the substituents on the carbocyclic ring, two different low-energy conformations of the crown ether are possible. Ligand 3 has been studied in solution by 1H NMR spectroscopy at different values of pH and temperature, showing that the conformation of the crown ether, and thus its complexing ability, is strongly pH-dependent. The solid-state structure of the ligand has been determined by X-ray diffraction.

Organometallic Nickel(II) Complexes Containing Thiolate and Dithiocarbamate Ligands

Synthesis and Reactivity of Ortho-Mercuriated and Ortho-Palladated Arylacetals and Cyclic and Acyclic Aryldithioacetals. New Examples of the Rearrangement of Acyclic Dithioacetal Aryl- to Dithioether Alkyl-Palladium Complexes

The arylmercurial [Hg{C6H3(CHO)2-2,5}Cl] (1) reacts with CH(OMe)3 or HS(CH2)2SH to give [Hg{C6H3{CH(OMe)2}2-2,5}Cl] (2) or [Hg(Ara)Cl] [Ara = C6H3{CH(SCH2CH2S)}2-2,5 (3a)], respectively. The mercur...

New Strategy for the Stereoselective Synthesis of Fluorinated β-Amino Acids

Racemic and chiral nonracemic alpha-substituted and alpha-unsubstituted beta-fluoroalkyl beta-amino acid derivatives 6 and 9 have been synthesized in two steps starting from fluorinated imidoyl chlorides 1 and ester enolates. This approach is based on the chemical reduction of previously obtained gamma-fluorinated beta-enamino esters 4 by using ZnI(2)/NaBH(4) in a nonchelated aprotic medium (dry CH(2)Cl(2)) as the reducing agent. A metal-chelated six-membered model has been suggested to explain the stereochemical outcome of the reduction reaction. The process takes place with high yields and with moderate to good diastereoselectivity. The best results related to diastereoselective reduction…

Enantioselective syntheses of dopaminergic (R)- and (S)-benzyltetrahydroisoquinolines.

Optically pure (1S,R)- and (1R,S)-benzyltetrahydroisoquinolines (BTHIQs), 12a,b as the major diastereomers, were prepared by stereoselective reduction of the isoquinolinium salt possessing (R)- and (S)-phenylglycinol as the chiral auxiliary, respectively. The absolute configurations of (1S,R)-13a hydrochloride (O-debenzoylated derivative from 12a) and (1R,S)-12b diastereomers were unambiguously determined by single-crystal X-ray analysis. Reductive removal of the chiral auxiliary group, subsequent N-propylation, and cleavage of the methylenedioxy group furnished the optically active catecholamines (1S)-16a and (1R)-16b in good overall yield. We have separately prepared for the first time pa…

Ortho-Metalated Primary Amines. 6.1 The First Synthesis of Six-Membered Palladacycles from Primary Amines Containing Electron-Withdrawing Substituents:  End of the Limiting Rules of Cope and Friedrich on Cyclopalladation of Benzyl- and Phenethylamines

When H 2 N(CH 2 ) 2 C 6 H 4 OMe-4 (RNH 2 ) and Pd(OAc) 2 are reacted in a 2:1 molar ratio, the complex [Pd(OAC) 2 (NH 2 R) 2 ] (1) is obtained. Complex 1 reacts with 1 equiv of Pd(OAc) 2 to give the dinuclear complex [Pd(OAc)(μ-OAc)(NH 2 R)] 2 (2). When complex 2 is heated in acetonitrile at 80 °C, the ortho-metalated complex [Pd{C 6 H 3 (CH 2 ) 2 NH 2 -2-OMe-5-κ 2 C,N}(μ-OAc)] 2 (3a) is obtained. Complex 3a is also prepared by refluxing RNH 2 and Pd(OAc) 2 in a 1:1 molar ratio in acetonitrile. Complex 3a reacts with NaBr or LiCl to afford the complexes [Pd{C 6 H 3 (CH 2 ) 2 NH 2 -2-OMe-5-κ 2 C,N}(μ-X)]2 (X = Cl (3b), Br (3c)). PPh 3 splits the acetate or halide bridge in complex 3a or 3b t…

Synthesis and Reactivity of 2-Aminophenylpalladium(II) Complexes: Insertion Reactions of Oxygen and Carbon Monoxide into Carbon−Palladium Bonds—New Examples of “Transphobia”

Insertion of CO into 2-aminophenylpalladium complexes leads to 2-aminobenzoylpalladium derivatives. When these compounds are forced to coordinate a carbon donor and a phosphane ligand in the trans position, a C−P coupling process or an insertion of oxygen occurs (see scheme). In this case, a dinuclear palladium complex containing a bridging anthranilato ligand is isolated.

Synthesis of terpenoid unsaturated 1,4-dialdehydes. Pi-facial selectivity in the Diels-Alder reaction of the 1-vinyl-2-methylcyclohexene moiety of polycyclic systems with DMAD.