Asymmetric Vinylogous Michael Addition Research Articles

Catalytic asymmetric conjugate addition of coumarins to unsaturated ketones catalyzed by a chiral-at-metal Rh(III) complex.

The first catalytic asymmetric vinylogous Michael addition of coumarins to unsaturated ketones catalyzed by chiral rhodium catalysts has been established. This strategy allowed the synthesis of a variety of highly enantioenriched compounds containing coumarin skeletons in 41-99% yields and 84-99% ee. The developed reaction enriches the chemistry of catalytic asymmetric vinylogous Michael additions of 3-cyano-4-methylcoumarins. Furthermore, the protocol showed obvious advantages in reaction enantioselectivity. When the chiral rhodium catalyst was reduced to 0.06 mol%, a Gram-level reaction was still achieved to provide the desired products with 99% ee.

Organocatalytic Asymmetric Vinylogous Michael Addition of Electron-Deficient Aryl Alkane Nucleophiles to Enals.

We report herein a protocol for an organocatalyzed asymmetric vinylogous Michael addition of aryl alkane nucleophiles with enals under base- and additive-free conditions. A series of allylic building blocks were obtained in 60%-93% yield and 88-99% ee with 20 mol % diphenylprolinol silyl ether as catalyst. This protocol has advantages such as excellent chemoselectivity and regioselectivity, good tolerance of functionalities, and simple reaction conditions.

Asymmetric Synthesis of Spiro-3,3'-cyclopropyl Oxindoles via Vinylogous Michael Initiated Ring Closure Reaction.

A novel organocatalytic cascade approach for the synthesis of spiro-cyclopropyl oxindole derivatives has been developed. The methodology is based on asymmetric vinylogous Michael addition of 4-nitroisoxazole derivatives to N-Boc isatylidene malonates followed by intramolecular alkylation. Its remarkable stereocontrol, wide substrate scope, and scalability highlight this new developed strategy. Moreover, this work represents the first example of vinylogous Michael initiated ring closure (MIRC) reaction for the synthesis of chiral 3,3'-cyclopropyl oxindole.

Catalytic Asymmetric Conjugate Addition of 2-Methyl-3,5-dinitrobenzoates to Unsaturated Ketones

Asymmetric catalytic vinylogous Michael addition of 2-methyl-3,5-dinitrobenzoates to unsaturated ketones catalyzed by chiral rhodium catalysts has been established. This strategy allowed the synthesis of a variety of optically pure compounds containing imidazole and 3,5-dinitrobenzene skeletons in 64-98% yields with 88-98% ee. The developed reaction not only represents highly asymmetric catalytic enantioselective vinylogous Michael addition employing 2-methyl-3,5-dinitrobenzoates as a building block but also enriches the chemistry of catalytic asymmetric vinylogous Michael addition of 2-methyl-3,5-dinitrobenzoates. Furthermore, the protocol showed obvious advantages in reaction activity and enantioselectivity. When the chiral rhodium catalyst was reduced to 0.06 mol %, the gram-level reaction was still achieved to provide the desired product with 95% ee.

Enantioselective direct vinylogous Michael addition for constructing enantioenriched γ,γ-dialkyl substituted butyrolactams and octahydroindoles.

A nickel(II)-catalyzed asymmetric direct vinylogous Michael addition of γ-alkyl monosubstituted α,β-unsaturated butyrolactams to α,β-unsaturated carbonyl compounds has been disclosed, affording γ,γ-dialkyl substituted butyrolactams in good yields and satisfactory enantioselectivities. A tandem catalytic asymmetric vinylogous Michael addition/intramolecular Michael addition has also been developed based on this reaction, which enabled the construction of enantioenriched octahydroindoles with three consecutive stereogenic carbon centers.

Direct catalytic asymmetric vinylogous Michael addition to construct an all-carbon quaternary center with 3-alkenyl-oxindoles

Direct catalytic asymmetric vinylogous Michael addition to construct an acyclic all-carbon quaternary center with novel 3-alkenyl-oxindoles.

Regioselective and diastereodivergent organocatalytic asymmetric vinylogous Michael addition

Regioselective and diastereodivergent γ-position asymmetric vinylogous Michael addition (AVMA) of cyclohex-2-enones to nitroalkenes and γ′-AVMA between cyclohex-3-enones and nitroalkenes.

Construction of Enantioenriched 9H-Fluorene Frameworks via a Cascade Reaction Involving Remote Vinylogous Dynamic Kinetic Resolution.

The benzylic C-H group of α,α-dicyanoolefins from 3-substituted 1-indanones could be significantly activated via transmission along the aromatic system, thus enabling dynamic kinetic resolution via a traditional reversible deprotonation-protonation process. Enantioenriched 9-substituted 9H-fluorene frameworks were finally constructed through an asymmetric vinylogous Michael addition to nitroolefins, followed by a cascade cyclization and oxidative aromatization process, under the catalysis of a chiral bifunctional thiourea-tertiary amine.

Asymmetric vinylogous Michael addition of 5-substituted-furan-2(3H)-ones to an α,β-unsaturated-γ-lactam.

The manuscript describes an utilization of 5-substituted-furan-2(3H)-ones as pronucleophiles in an asymmetric vinylogous Michael addition to an α,β-unsaturated-γ-lactam, thus leading to hybrid molecules possessing γ-lactam and butenolide structural motifs. The transformation utilizes two potentially vinylogous pronucleophiles and has been realized by simultaneous activation of both substrates by a bifunctional organocatalyst derived from a cinchona alkaloid. Reaction occurs in a highly enantio- and diastereoselective manner and the synthetic potential of the target products has been confirmed in stereoselective transformations.

Organocatalytic asymmetric vinylogous 1,4-addition of α,α-Dicyanoolefins to chalcones under a bio-based reaction media: Discovery of new Michael adducts with antiplasmodial activity

The organocatalysed asymmetric vinylogous Michael addition of α,α-dicyanoolefins to α,β-unsaturated aldehydes and ketones have been reported in the last decade, however, chalcones have been poorly explored. Moreover, a considerable part of the publications in this theme still employs undesirable solvents, such as toluene and THF, with concerns related to health and environmental safety. We report herein the use of a bifunctional catalyst derived from a Cinchona alkaloid to perform the enantio- and diastereoselective Michael addition of α,α-dicyanoolefins to chalcones using 2-MeTHF as solvent. The Michael adducts were obtained in moderate to good yields and were evaluated for their antiplasmodial and cytotoxic activity.

A chiral-at-metal asymmetric catalyzed vinylogous Michael addition of ortho-methyl aromatic nitro compounds for isoxazole derivative synthesis

A chiral-at-metal rhodium(iii) complex catalyzed asymmetric vinylogous Michael addition of 5-methyl 4-nitroisoxazoles with α,β-unsaturated 2-acyl imidazoles has been developed, delivering the corresponding adducts with up to 96% yield and 97% ee.

Enantioselective Organocatalyzed Vinylogous Michael Reactions of 3-Alkylidene Oxindoles with Enals.

An efficient asymmetric vinylogous Michael addition of 3-alkylidene oxindoles and enals has been achieved using a chiral TBS-protected diphenylprolinol catalyst. The γ-substituted alkylidene oxindoles obtained bear a chiral tertiary center and are afforded in moderate to good yields and good to excellent enantioselectivities.

ChemInform Abstract: Enantioselective Synthesis of Chiral α,β‐Unsaturated γ‐Substituted Butyrolactams by Organocatalyzed Direct Asymmetric Vinylogous Michael Addition of α,β‐Unsaturated γ‐Butyrolactam to 2‐Enoylpyridines.

AbstractThe products are formed with excellent diastereo and enantioselectivities.

Enantioselective synthesis of chiral α,β-unsaturated γ-substituted butyrolactams by organocatalyzed direct asymmetric vinylogous Michael addition of α,β-unsaturated γ-butyrolactam to 2-enoylpyridines.

An organocatalyzed direct asymmetric vinylogous Michael addition reaction of α,β-unsaturated γ-butyrolactam to 2-enoylpyridines has been developed with a chiral bifunctional amine-squaramide as the catalyst. This approach provides easy access to a series of optically active α,β-unsaturated γ-substituted butyrolactams in high yields (up to 99%) with excellent diastereoselectivities (up to >99 : 1) and enantioselectivities (up to >99% ee).

ChemInform Abstract: Organocatalytic Asymmetric Vinylogous Michael Addition of 3‐(2‐Oxoindolin‐3‐ylidene)butanoates to Nitroalkenes Catalyzed by a Bifunctional Cinchona‐Based Squaramide.

AbstractAn efficient, enantioselective, vinylogous Michael addition of 3‐(2‐oxoindolin‐3‐ylidene)butanoates to nitroalkenes is presented which is catalyzed by a cinchona alkaloid‐derived squaramide.

ChemInform Abstract: Organocatalyzed Asymmetric Vinylogous Michael Reactions of 3,5‐Dialkyl‐Substituted 4‐Nitroisoxazoles: A Direct Method for the Synthesis of Chiral Isoxazole Derivatives.

AbstractVarious highly functionalized chiral isoxazole derivatives are obtained in excellent enantioselectivities by direct asymmetric vinylogous Michael addition of 3,5‐dialkyl‐substituted 4‐nitroisoxazoles with α,β‐unsaturated aldehydes using a diphenylprolinol Tbs ether as organocatalyst.

ChemInform Abstract: Direct Asymmetric Vinylogous Michael Addition of 3‐Alkylidene Oxindoles to Chalcones Catalyzed by a Chiral N,N′‐Dioxide Ytterbium(III) Complex.

A chiral ytterbium(III)–N,N′-dioxide catalyst system has been developed for the catalytic direct asymmetric vinylogous Michael addition of 3-alkylidene oxindoles to chalcones, delivering the γ-substituted alkylideneoxindoles in high yields, enantioselectivities and good Z/E selectivities under mild reaction conditions.

Organocatalytic Asymmetric Vinylogous Michael Addition of 3‐(2‐Oxoindolin‐3‐ylidene)butanoates to Nitroalkenes Catalyzed by a Bifunctional Cinchona‐Based Squaramide

AbstractThe highly efficient asymmetric vinylogous Michael addition of 3‐(2‐oxoindolin‐3‐ylidene)butanoates to nitroalkenes, catalyzed by a cinchona‐based squaramide, is described. The enantioselectivity (up to 99 % ee) and diastereoselectivity (>20:1 d.r.) of the reaction is excellent.

ChemInform Abstract: Organocatalytic Asymmetric Vinylogous Michael Addition of 3‐Alkylidene Oxindoles to α‐Substituted β‐Nitroacrylates: Facile Construction of a Chiral All‐Carbon Quaternary Center.

AbstractThe stereocenters and alkene geometries of the products (III), (V), and (VII) are precisely controlled by the employed bifunctional squaramide catalyst.

Organocatalyzed Asymmetric Vinylogous Michael Reactions of 3,5‐Dialkyl‐Substituted 4‐Nitroisoxazoles: A Direct Method for the Synthesis of Chiral Isoxazole Derivatives

AbstractThe direct asymmetric vinylogous Michael addition of 3,5‐dialkyl‐substituted 4‐nitroisoxazoles with α,β‐unsaturated aldehydes catalyzed by a diphenylprolinol TBS ether organocatalyst is described, giving products with moderate to good yields and up to excellent enantioselectivities (96% ee). This approach provides an easy access to highly functionalized chiral isoxazole derivatives.magnified image