0000000001311069
AUTHOR
Javier Miró
Gold catalyzed stereoselective tandem hydroamination–formal aza-Diels–Alder reaction of propargylic amino esters
A gold-catalyzed tandem intramolecular hydroamination-formal aza-Diels-Alder reaction of propargylic amino esters is described. The overall process leads to the formation of a tetracyclic framework as a single diastereoisomer, with the creation of four bonds and five stereocenters.
ChemInform Abstract: Gold Catalyzed Stereoselective Tandem Hydroamination-Formal Aza-Diels-Alder Reaction of Propargylic Amino Esters.
The overall sequence of the tandem reaction presented here leads to nitrogen-containing tetracycles under formation of 4 bonds and five stereocenters, in most cases as single diastereoisomers.
ChemInform Abstract: Gold-Catalyzed Povarov-Type Reaction of Fluorinated Imino Esters and Furans.
A gold-catalyzed Povarov-type reaction of fluorinated imino esters and furans is described. The process, which takes place in dichoromethane at room temperature, gives rise to novel fluorinated tetrahydrofuran-fused tetrahydroquinolines in good yields and moderate levels of diastereoselectivity in a very simple manner. The reported examples expand the versatility of the Povarov reaction to unprecedented fluorinated substrates, generating scaffolds that contain quaternary α-amino acid units.
ChemInform Abstract: Differential Reactivity of Fluorinated Homopropargylic Amino Esters vs Gold(I) Salts. The Role of the Nitrogen Protecting Group.
The gold(I)-catalyzed hydroarylation/isomerization reaction of N-protected homopropargyl amino esters (III) gives quinoline derivatives of type (IV).
ChemInform Abstract: Fluorine and Gold: A Fruitful Partnership
Gold-catalyzed reactions have witnessed an exponential growth in the past decade. When the unique modes of activation exhibited by gold species meet species with either fluorinated building blocks or fluorinating reagents, new opportunities arise for the development of new methodologies in fluoroorganic chemistry. Indeed, gold and fluorine truly formed a very fruitful partnership, and different types of reactivity emerged from their combination. This review gives an overview of such endeavors. The special properties imparted by fluorine to organic molecules have been exploited in gold-catalyzed processes, allowing for the generation of unprecedented fluorinated chemical entities. Thus, the …
ChemInform Abstract: Gold-Catalyzed Tandem Hydroamination/Formal Aza-Diels-Alder Reaction of Homopropargyl Amino Esters: A Combined Computational and Experimental Mechanistic Study.
Under optimized conditions, the title reaction leads to formation of a tetracyclic nitrogen-containing framework with generation of 4 bonds and 5 stereocenters.
One-pot cross-enyne metathesis (CEYM)-Diels-Alder reaction of gem-difluoropropargylic alkynes.
Propargylic difluorides 1 were used as starting substrates in a combination of cross-enyne metathesis and Diels–Alder reactions. Thus, the reaction of 1 with ethylene in the presence of 2nd generation Hoveyda–Grubbs catalyst generates a diene moiety which in situ reacts with a wide variety of dienophiles giving rise to a small family of new fluorinated carbo- and heterocyclic derivatives in moderate to good yields. This is a complementary protocol to the one previously described by our research group, which involved the use of 1,7-octadiene as an internal source of ethylene.
Correction to Fluorine and Gold: A Fruitful Partnership
Fluorine and Gold: A Fruitful Partnership
Gold-catalyzed reactions have witnessed an exponential growth in the past decade. When the unique modes of activation exhibited by gold species meet species with either fluorinated building blocks or fluorinating reagents, new opportunities arise for the development of new methodologies in fluoroorganic chemistry. Indeed, gold and fluorine truly formed a very fruitful partnership, and different types of reactivity emerged from their combination. This review gives an overview of such endeavors. The special properties imparted by fluorine to organic molecules have been exploited in gold-catalyzed processes, allowing for the generation of unprecedented fluorinated chemical entities. Thus, the …
Differential reactivity of fluorinated homopropargylic amino esters vs gold(I) salts. The role of the nitrogen protecting group
The reaction of several homopropargyl amino esters 4, bearing aromatic substituents and a benzyl group as nitrogen substituents, with gold(I) salts gave rise to fluorinated quinolines 6 in a tandem hydroarylation-isomerization process. On the other hand, homopropargyl amino esters 7 containing a carbamate group underwent the carbonyl addition over the triple bond in the presence of gold(I) salts, rendering fluorinated oxazines 8. The use of chiral sulfoxides allowed us to develop the asymmetric version of this protocol. This two processes complete the differential reactivity showed by these types of susbtrates, depending on the nature of the nitrogen protecting group. (C) 2014 Elsevier B.V.…
1,7-Octadiene-Assisted Tandem Multicomponent Cross-Enyne Metathesis (CEYM)-Diels-Alder Reactions: A Useful Alternative to Mori’s Conditions
The use of 1,7-octadiene as an in situ source of ethylene led us to develop a novel multicomponent tandem cross-enyne metathesis (CEYM)-Diels-Alder reaction. The process can be considered a relay metathesis, in which the ethylene liberated in the ring-closing metathesis (RCM) of 1,7-octadiene initiates the tandem sequence. Aliphatic, aromatic, and fluorinated alkynes and several dienophiles are compatible with the process, which is particularly efficient with aromatic alkynes. This methodology constitutes a useful variant of Mori's conditions in CEYM-related reactions.
ChemInform Abstract: Tandem Cross Enyne Metathesis (CEYM)-Intramolecular Diels-Alder Reaction (IMDAR). An Easy Entry to Linear Bicyclic Scaffolds.
A new tandem cross enyne metathesis (CEYM)–intramolecular Diels–Alder reaction (IMDAR) has been carried out. It involves conjugated ketones, esters or amides bearing a remote olefin and aromatic alkynes as the starting materials. The overall process enables the preparation of a small family of linear bicyclic scaffolds in a very simple manner with moderate to good levels of diastereoselectivity. This methodology constitutes one of the few examples that employ olefins differently than ethylene in tandem CEYM–IMDAR protocols.
ChemInform Abstract: A New Tandem Cross Metathesis-Intramolecular Aza-Michael Reaction for the Synthesis of α,α-Difluorinated Lactams.
Difluorinated amides are treated with methyl vinyl ketone or analogous esters to produce the desired γ- and δ-lactam units including optically active versions.
Enantioselective Palladium-Catalyzed Oxidative β,β-Fluoroarylation of α,β-Unsaturated Carbonyl Derivatives
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim The site-selective palladium-catalyzed three-component coupling of deactivated alkenes, arylboronic acids, and N-fluorobenzenesulfonimide is disclosed herein. The developed methodology establishes a general, modular, and step-economical approach to the stereoselective β-fluorination of α,β-unsaturated systems.
Gold-Catalyzed Tandem Hydroamination/Formal Aza-Diels-Alder Reaction of Homopropargyl Amino Esters: A Combined Computational and Experimental Mechanistic Study
A tandem gold-catalyzed hydroamination/formal aza-Diels-Alder reaction is described. This process, which employs quaternary homopropargyl amino ester substrates, leads to the formation of an intrincate tetracyclic framework and involves the generation of four bonds and five stereocenters in a highly diastereoselective manner. Theoretical calculations have allowed us to propose a suitable mechanistic rationalization for the tandem protocol. Additionally, by studying the influence of the ligands on the rate of the gold-catalyzed reactions, it was possible to establish optimum conditions in which to perform the process with a variety of substituents on the amino ester substrates. Notably, the …
Cross-Metathesis/Intramolecular (Hetero-)Michael Addition: A Convenient Sequence for the Generation of Carbo- and Heterocycles
The high stability and functional group compatibility of ruthenium carbene complexes confer them a great ability to catalyze domino processes. For this reason, the combination of metathesis reactions with additional transformations in a domino fashion has been exploited extensively, with the result of expanding the utility of ruthenium carbene complexes beyond that of just olefin metathesis. Among those domino processes, it is worth mentioning the sequence of cross-metathesis/intramolecular Michael addition, which allows for the generation of a wide variety of carbo- and heterocycles in a very simple manner, taking advantage of the benefits of domino reactions. Carbon-, oxygen- and nitrogen…
Tandem gold self-relay catalysis for the synthesis of 2,3-dihydropyridin-4(1 H)-ones: combination of σ and π Lewis acid properties of gold salts.
The dual ability of gold salts to act as π- and σ Lewis acids has been exploited in a tandem self-relay catalysis. Thus, triphenylphosphanegold(I) triflate mediated the intramolecular carbonyl addition of the amide functionality of homoprogargyl amides to a triple bond. The formation of a σ complex of the gold salt with the intermediate oxazine promoted a nucleophilic addition followed by a Petasis-Ferrier rearrangement. This tandem protocol, catalyzed by the same gold salt under the same reaction conditions, gave rise to the efficient synthesis of 2,3-dihydropyridin-4-(1 H)-ones, which contain a cyclic quaternary α-amino acid unit. The asymmetric version was performed by generating the sta…
Tandem cross enyne metathesis (CEYM)–intramolecular Diels–Alder reaction (IMDAR). An easy entry to linear bicyclic scaffolds
A new tandem cross enyne metathesis (CEYM)–intramolecular Diels–Alder reaction (IMDAR) has been carried out. It involves conjugated ketones, esters or amides bearing a remote olefin and aromatic alkynes as the starting materials. The overall process enables the preparation of a small family of linear bicyclic scaffolds in a very simple manner with moderate to good levels of diastereoselectivity. This methodology constitutes one of the few examples that employ olefins differently than ethylene in tandem CEYM–IMDAR protocols.
Gold-Catalyzed Povarov-Type Reaction of Fluorinated Imino Esters and Furans
A gold-catalyzed Povarov-type reaction of fluorinated imino esters and furans is described. The process, which takes place in dichoromethane at room temperature, gives rise to novel fluorinated tetrahydrofuran-fused tetrahydroquinolines in good yields and moderate levels of diastereo-selectivity in a very simple manner. The reported examples expand the versatility of the Povarov reaction to unprecedented fluorinated substrates, generating scaffolds that contain quaternary alpha-amino acid units.
A New Tandem Cross Metathesis-Intramolecular Aza-Michael Reaction for the Synthesis of α,α-Difluorinated Lactams
A new tandem cross metathesis–intramolecular aza-Michael reaction in which an α,α-difluorinated amide serves as a source of nucleophilic nitrogen is described. This process gives rise to a new family of fluorinated γ- and δ-lactams. The tandem protocol is catalyzed by the Hoveyda–Grubbs second-generation ruthenium catalyst with titanium(IV) tetraisopropoxide as a co-catalyst and it is highly efficient when conjugated ketones are used as the Michael acceptors. With conjugated esters, however, it is necessary to perform a step-by-step procedure in which the cyclization event is activated by the addition of a base. An asymmetric version of the process is also evaluated.
Stereoselective Access to Fluorinated and Non-fluorinated Quaternary Piperidines: Synthesis of Pipecolic Acid and Iminosugar Derivatives
The preparation of optically pure quaternary piperidines, both fluorinated and non-fluorinated, has been achieved from a chiral imino lactone derived from (R)-phenylglycinol. In the case of the fluorinated derivatives, the addition of (trifluoromethyl)trimethylsilane (TMSCF(3)) followed by iodoamination and migration of the CF(3) group allowed access to four derivatives of α-(trifluoromethyl)pipecolic acid. A theoretical study of the CF(3)-group rearrangement has been carried out to help establish the reaction mechanism of this uncommon transformation. Moreover, a route to trifluoromethyl-substituted iminosugars was also developed through the diastereoselective dihydroxylation of suitable s…
ChemInform Abstract: Enantioselective Palladium-Catalyzed Oxidative β,β-Fluoroarylation of α,β-Unsaturated Carbonyl Derivatives.
The site-selective palladium-catalyzed three-component coupling of deactivated alkenes, arylboronic acids, and N-fluorobenzenesulfonimide is disclosed herein. The developed methodology establishes a general, modular, and step-economical approach to the stereoselective β-fluorination of α,β-unsaturated systems.
ChemInform Abstract: 1,7-Octadiene-Assisted Tandem Multicomponent Cross-Enyne Metathesis (CEYM)-Diels-Alder Reactions: A Useful Alternative to Mori′s Conditions.
The protocol relies on a relay metathesis process, in which 1,7-octadiene acts as an in situ source of ethylene.
CCDC 984448: Experimental Crystal Structure Determination
Related Article: Santos Fustero, Javier Miró, María Sánchez-Roselló, Carlos del Pozo|2014|Chem.-Eur.J.|20|14126|doi:10.1002/chem.201403340