Organocatalytic Asymmetric Michael Addition Research Articles

Preparation of Indolin-3-one-Containing 1,4-Naphthoquinone Derivatives via Organocatalytic Asymmetric Michael Addition Reaction.

This article explores the asymmetric Michael addition reaction of 2-hydroxy-1,4-naphthoquinone and indole-3-ones catalyzed by cinchona alkaloids. This strategy utilizes 2-hydroxy-1,4-naphthoquinone and easily prepared indole-3-one as substrates, resulting in the synthesis of 23 unprecedented indolin-3-ones bearing a 1,4-naphthoquinone unit at the C2 position of indole under simple and mild reaction conditions, with up to 88% yield, 98% ee, and >20:1 dr.

Enantioselective synthesis of Benzofurans bearing adjacent quaternary and tertiary carbon stereocenters by Organocatalytic asymmetric Michael addition of 3-methylbenzofuran −2(3H)-ones to azadienes

An enantioselective Michael addition of 3-methylbenzofuran-2(3H)-ones to azadienes catalyzed by an L-tert- leucine derived squaramide catalyst was developed, by which a variety of benzofuranones bearing adjacent quaternary and tertiary carbon centers were obtained in high yields (up to 98%) with moderate to excellent diastereoselectivities (up to 97:3) and enantioselectivities (up to 97%).

Organocatalytic asymmetric Michael addition reaction of aldehydes with 2-furanones: experimental, applications and DFT studies

Organocatalytic asymmetric Michael additions of aldehydes to 2-furanones are successfully conducted and have been applied to the synthesis of vorapaxar's analogues.

Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole.

An asymmetric Michael reaction between cyclopentane-1,2-dione and alkylidene oxindole was studied in the presence of a multifunctional squaramide catalyst. Michael adducts were obtained in high enantioselectivities and in moderate diastereoselectivities.

Organocatalytic Asymmetric Michael Addition in Aqueous Media by a Hydrogen-Bonding Catalyst and Application for Inhibitors of GABAB Receptor

Catalysts based on (R, R)-1,2-diphenylethylenediamine are, as chiral organic catalysts, applied to the asymmetric Michael addition to α, β-unsaturated nitroalkenes under neutral conditions. The role of an aqueous medium for organic catalytic activity can be reversed concerning hydrophilic-hydrophobic function depending on the reaction conditions. In this study, to provide an environmentally friendly system, the thiourea-based catalyst substituted with 3,5-(CF3)2-Ph was used in water solvents. The hydrophobic effect of the substituent provided fast reaction, high chemical yield, and mirror-image selectivity. This reaction allowed the preparation of GABAB agonists in an optically pure manner. Additionally, GABA (γ-aminobutyric acid) analogs such as baclofen and phenibut were synthesized as R-type S-type with high optical purity.

Recent Advances in Organocatalytic Asymmetric Michael Addition Reactions to α, β‐Unsaturated Nitroolefins

AbstractAn organocatalyzed asymmetric Michael addition reaction has been established as the most relevant and dynamic research area for the construction of chiral carbon‐carbon and carbon‐heteroatom bond. In the current scenario, rapid revolutions on asymmetric Michael addition to nitroolefins have been explored by taking advantage of newly developed chiral organocatalysts. Moreover, nitroolefins have proven as well‐known Michael acceptors for providing various structurally essential nitro‐functionalized frameworks. In addition to this, remarkable stereoselectivity has been achieved in this asymmetric process by following different mechanistic pathways that involve enamine, iminium ion intermediate formation and bifunctional H‐bonding interaction. So, we have discussed the recent advancements of organocatalytic Michael addition reactions to α, β‐unsaturated nitroolefins from the year 2016 to 2020.

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.

Organocatalytic Asymmetric Synthesis of an Advanced Intermediate of (+)-Sarain A.

The first organocatalytic asymmetric synthesis of an advanced intermediate of (+)-sarain A was achieved. This approach featured the employment of an organocatalytic asymmetric Michael addition reaction and a nitrogen-to-carbon chirality transfer to forge three chiral centers, as well as a catalytic hydrosilylation for the chemoselective reduction of a key lactam intermediate. The tricyclic intermediate contained all the required functionalities for elaborating into (+)-sarain A.

Organocatalytic Asymmetric Michael Addition of Ketones to α, β-Unsaturated Nitro Compounds

An organic catalyst “(R, R)-1,2-diphenylethylenediamine(DPEN) derivative’’ was devel-oped as a chiral bifunctional organocatalyst and applied for asymmetric Michael additions of aromatic ketones to trans-β-nitroalkene compounds under neutral conditions. The isopropyl-subs-tituted thiourea catalyst in neutral condition provides high chemical yield and enantioselectivities (ee) (up to 96% yield, 98% ee).

Organocatalytic Asymmetric Michael Addition of Pyrazol-5-ones to β-Trifluoromethyl-α,β-unsaturated Ketones: Stereocontrolled Construction of Vicinal Quaternary and Tertiary Stereocenters.

An efficient organocatalytic asymmetric Michael addition of 4-substituted-pyrazol-5-ones to β-trifluoromethyl-α,β-unsaturated ketones was developed. In the presence of a dipeptide-based urea-amide tertiary amine catalyst, an array of chiral products containing pyrazolone and trifluoromethyl moieties bearing vicinal quaternary and tertiary stereocenters were obtained in good yields with good to excellent enantioselectivity and diastereoselectivity (up to 95% yields, up to 97% ee, and >20:1 d.r.). Moreover, the reaction was compatible with 4-substituted-pyrazol-5-ones containing either aryl or alkyl group at the C3 position.

Asymmetric Organocatalytic Michael Addition–Cyclisation Cascade of Cyclopentane-1,2-dione with Alkylidene Malononitriles

An asymmetric organocatalytic cascade reaction between cyclopentane-1,2-diones and alkylidene malononitriles affords highly substituted 4H-pyrans in moderate to high enantiomeric excess. The selective reduction of a bridged double bond leads to the formation of cis-substituted cyclopentanone with three contiguous stereogenic centres.

Kinetic Resolution of Axially Chiral 2‐Nitrovinyl Biaryls Catalyzed by a Bifunctional Thiophosphinamide

AbstractAn efficient kinetic resolution of axially chiral 2‐nitrovinyl biaryls was realized through organocatalytic asymmetric Michael addition of acetone to the nitroolefin moiety. Under the catalysis of a chiral thiophosphinamide derived from (1R,2R)‐1,2‐diphenylethane‐1,2‐diamine, racemic 2‐nitrovinyl biaryls were converted into highly enantiomer‐enriched 2‐nitrovinyl biaryls in 13–44% yields and a pair of separable Michael addition products bearing both axial and central chiralities in excellent stereocontrol. This represents the first successful application of asymmetric Michael addition of nitroolefins in kinetic resolution of axially chiral biaryls.magnified image

Organocatalytic asymmetric Michael addition between 3-subsituted oxindoles and enals catalyzed by camphor sulfonyl hydrazine.

Organocatalytic asymmetric Michael addition between 3-substituted oxindoles and enals catalyzed by chiral camphor sulfonyl hydrazines (CaSHs) has been developed. A wide range of 3-substituted oxindoles and enals were successfully used, giving the corresponding 3,3-disubstituted oxindoles containing vicinal stereogenic carbon centers in good yields with good to excellent enantioselectivities and moderate to good diastereoselectivities (up to 89% yield, 99% ee and 99 : 1 dr).

Combining organocatalysis with photoorganocatalysis: photocatalytic hydroacylation of asymmetric organocatalytic Michael addition products

Organocatalysis and photoorganocatalysis are two areas of synthetic methodology that have been successfully combined.

Enantioselective aminocatalysis: Michael addition of unactivated ketones to nitroolefins catalyzed by D-fructose derived monofunctional primary amine

Organocatalytic asymmetric Michael addition is considered among the most extensively studied, yet challenging stereoselective reactions due to the fact that the electrophilic prochiral carbon in Michael acceptor lies away from stereodirecting groups of the catalyst. Although there is a report on stereoselective organocatalysis in Michael addition employing monofunctional secondary amine, the use of monofunctional primary amine for the said reaction is not reported till date. In fact, no monofunctional aminocatalyst is reported yet for the synthesis $$\upgamma $$ -nitro carbonyl compounds. Here we report our preliminary results on the enantioselective Michael addition of different ketones to nitro olefins catalysed by monofunctional primary amine (1) derived from d-fructose. Monofunctional primary amine is used for the first time as catalyst for stereoselective Michael addition reaction of different ketones to nitro olefins to synthesize $$\upgamma $$ -nitro carbonyl compounds.

Organocatalytic asymmetric Michael addition of pyrazoleamides to β-phthalimidonitroethene

A highly organocatalyzed asymmetric Michael addition reaction of pyrazoleamides to β-phthalimidonitroethene has been developed with a chiral bifunctional thiourea-tertiary amine as the catalyst. A wide range of γ-nitro β-amino amides were readily obtained in good to excellent yields with high diastereo- and enantioselectivities (up to 99% yield, 99% ee and >20:1 dr). The large scale experiment and transformation of the product have also been demonstrated.

Asymmetric Organocatalytic Michael Addition–Cyclization Cascade of Cyclopentane-1,2-dione with Substituted α,β-Unsaturated Aldehydes

An asymmetric organocatalytic Michael addition–cyclization cascade reaction has been developed using cyclopentane-1,2-dione as a Michael donor and α,β-unsaturated aldehydes as Michael acceptors. Bicyclic hemiacetals were obtained in excellent yields and enantioselectivities. On the basis of the results, a one-pot reaction has been developed to obtain chiral 3-substituted cyclopentane-1,2-diones and substituted dihydropyrans in good yields and excellent enantioselectivity.

Construction of 3,4‐Dihydrocoumarin Derivatives with Adjacent Quaternary and Tertiary Stereocenters: Organocatalytic Asymmetric Michael Addition of 2‐Oxochroman‐3‐carboxylate Esters to trans‐β‐Nitroolefins

AbstractAn asymmetric Michael addition of 2‐oxochroman‐3‐carboxylate esters to trans‐β‐nitroolefins is described. This strategy can give direct access to dihydrocoumarin derivatives bearing adjacent quaternary and tertiary stereocenters with up to >99% yield, >20:1 dr, and >99% ee. The adduct was further transformed to a spiro‐dihydrocoumarin compound in three steps with good yield.magnified image

ChemInform Abstract: Organocatalytic Asymmetric Michael Addition of 3‐Pyrrolyloxindoles to β‐Phthalimidonitroethene for the Synthesis of 3,3′‐Disubstituted Oxindoles Bearing Contiguous 3,α,β‐Triamino Functionality.

An organocatalytic asymmetric Michael addition reaction of 3-pyrrolyloxindoles to β-phthalimidonitroethene has been developed with a bifunctional thiourea–tertiary amine as the catalyst. A range of 3,3′-disubstituted oxindoles bearing contiguous 3,α,β-triamino functionality could be obtained in high yields with good diastereoselectivities and high enantioselectivities (up to 99% yield, 99:1 dr, and 98% ee). The higher reactivity of β-phthalimidonitroethene compared to the reactivity of ordinary nitroalkenes in the reaction with 3-pyrrolyloxindoles was demonstrated by contrast experiments.

ChemInform Abstract: Organocatalytic Asymmetric Michael Addition of α‐Alkylidene Succinimides to Nitrostyrenes.

AbstractA squaramide‐catalyzed enantioselective conjugate addition reaction of alkylidenesuccinimides with β‐nitrostyrenes and a nitro diene gives the corresponding alkylidene(3‐nitropropyl)succinimides in good to excellent yields with high to excellent diastereoselectivities and enantioselectivities.