Highly efficient bifunctional organocatalysts for the asymmetric Michael addition of ketones to nitroolefins

A type of secondary-secondary-tertiary triamine bifunctional organocatalysts have been properly designed and synthesized. In our study, the designed catalyst (S)-N-(pyrrolidin-2-ylmethyl)pyridin-2-amine 5 has been shown to be highly efficient to promote the asymmetric Michael addition of ketones to nitroolefins at room temperature, which afforded the corresponding adducts in excellent diastereoselectivities (up to 99:1 dr) and enantioselectivities (up to >99% ee).     

Highly enantioselective addition of ketones to nitroolefins catalyzed by new thiourea-amine bifunctional organocatalysts

A new and effective organocatalytic system: primary amine derived chiral thiourea catalyst and AcOH-H2O additive, which converts different ketones to gamma-nitroketones in high yields (82-99%) and enantioselectivities (90-99%) has been described.     

Pyrrolidine-linker-camphor assembly: bifunctional organocatalysts for efficient Michael addition of cyclohexanone to nitroolefins under neat conditions

A simple and convenient strategy was developed to synthesize a new class of pyrrolidinyl-camphor based bifunctional organocatalysts possessing varying functional linkers. Catalytic screening of these camphor-pyrrolidine linked derivatives for asymmetric Michael reaction of cyclohexanone with β-nitrostyrene was carried out. Various aryl- and heteroaryl-nitroolefins, ketones as well as aldehydes gave the corresponding Michael adducts in high chemical yields (up to 95%) and exceptionally high diastereo-(syn/anti up to 99:1) and enantioselectivity (up to 95%) using catalyst 6 under solvent-free conditions.     

Enantioselective Michael reaction of malonates to nitroolefins catalyzed by bifunctional organocatalysts

Michael reaction of malonates to nitroolefins with chiral bifunctional organocatalysts, bearing both a thiourea and tertiary amino group, afforded Michael adducts with high yields and enantioselectivities (up to 95%, up to 93% ee).     

Novel chiral ammonium ionic liquids as efficient organocatalysts for asymmetric Michael addition of aldehydes to nitroolefins

Two chiral ammonium ionic liquids 1a and 1b have been newly synthesized from commercially available (+)-cis-2-benzamidocyclohexanecarboxylic acid. These CILs have been demonstrated to be efficient organocatalysts for asymmetric Michael addition of aldehydes to nitroolefins with excellent yields (up to 99%), high enantioselectivities (up to 90%) and modest to high diastereoselectivities (syn/anti ratio up to 99/1).     

Novel and highly efficient bifunctional calixarene thiourea derivatives as organocatalysts for enantioselective Michael reaction of nitroolefins with diketones

New bifunctional calixarene thiourea organocatalysts were synthesized and applied in catalytic asymmetric Michael addition of acetylacetone to various nitroolefins at room temperature. The corresponding adducts were obtained in good to excellent yields with excellent enantioselectivities (up to 92% ee). The present research demonstrates the advantages of incorporating two stereocontrolling structures into a single catalyst. Notably, it offers a simple and convenient doubly stereocontrolled approach for the catalytic asymmetric synthesis of a chiral organic molecule.     

Phosphine-boronates: efficient bifunctional organocatalysts for Michael addition

Phosphine-boronates R(2)P(o-C(6)H(4))B(OR')(2) have been evaluated as bifunctional organocatalysts for the Michael addition of malonate pronucleophiles to methylvinylketone. The presence of the Lewis acidic boron center adjacent to phosphorus significantly improves catalytic performance. Isolation and complete characterization of a key intermediate, namely a β-phosphonium enolate, substantiate the role of the Lewis acidic moiety in the catalytic process.     

Novel 2-pyridone synthesis via nucleophilic addition of malonic esters to alkynyl imines

[reaction: see text] A novel 2-pyridone synthesis via nucleophilic addition of malonic esters to alkynyl imines has been developed. The reaction of dialkylalkyl sodiomalonates with alkynyl imines provided 2-pyridones in good to excellent yields.     

Self-assembled proline-amino thioureas as efficient organocatalysts for the asymmetric Michael addition of aldehydes to nitroolefins

A small co-catalyst library of amino thioureas has been established from chiral 1,3-diamines. These bifunctional thioureas can form assemblies with proline to cooperatively catalyze the asymmetric Michael addition of aldehydes to nitroolefins. Both the reaction rate (up to 98% yield for 18 h) and the enantioselectivity (up to 94% ee) were significantly improved upon in less polar solvents.     

Novel guanidinyl pyrrolidine salt-based bifunctional organocatalysts: application in asymmetric conjugate addition of malonates to enones

Novel guanidinyl pyrrolidine salts are useful bifunctional organocatalysts for the asymmetric addition of malonates to enones. These organocatalysts are effective under a wide range of reaction conditions and afford products in high yield and enantioselectivity.     

Chiral amines as organocatalysts for asymmetric conjugate addition to nitroolefins and vinyl sulfones via enamine activation

Over the last decade the potential of organocatalysis has successfully been demonstrated. In particular, chiral amines such as pyrrolidine analogues have emerged as a broadly applicable class of organocatalyst for asymmetric conjugate addition via enamine activation. This Feature Article documents the development of these catalysts, emphasizing the design and mechanistic features that supply high selectivity in asymmetric Michael reactions.     

Michael additions in water of ketones to nitroolefins catalyzed by readily tunable and bifunctional pyrrolidine-thiourea organocatalysts

An operationally trivial and environmentally benign procedure for direct Michael addition has been developed. The reaction of various ketones with nitroolefins can be performed in water to afford the corresponding nitro compounds in high yields in the presence of a pyrrolidine-thiourea organocatalyst at 35 °C. The reaction exhibits a high stereoselectivity, with high enantioselectivities (up to 99%) as well as diastereoselectivities (up to 99:1) being achieved under the optimal conditions.     

Highly enantioselective Michael addition of aldehydes to nitroolefins catalyzed by primary amine thiourea organocatalysts

Asymmetric Michael addition reactions of aldehydes to nitroolefins have been successfully initiated by a series of primary amine thiourea bifunctional catalysts, with high enantioselectivities (90-98% ee) and excellent yields (80-96%). The privileged quinine scaffold was found to be essential to the reaction efficiency and enantioselectivity.     

Highly enantioselective conjugate addition of fluoromalonates to nitroalkenes using bifunctional organocatalysts

The enantioselective conjugate addition of fluoromalonates to aromatic nitroalkenes catalyzed by chiral amine-thiourea bifunctional organocatalysts generated a stereocenter at the carbon bearing the aromatic group and an adjacent prochiral center from the fluoromalonate. Treatment of fluoromalonates with aromatic nitroalkenes under mild reaction conditions afforded the corresponding 2-fluoro-2-(2-nitro-1-arylethyl)malonates with high yields (72-93%) and excellent enantioselectivities (91-98% ee).     

Highly enantioselective conjugate addition of nitromethane to chalcones using bifunctional cinchona organocatalysts

Cinchona alkaloid-derived chiral bifunctional thiourea organocatalysts were synthesized and applied in the Michael addition between nitromethane and chalcones with high ee and chemical yields.     

Chiral squaramide as multiple H-bond donor organocatalysts for the asymmetric Michael addition of 1,3-dicarbonyl compounds to nitroolefins

A series of chiral bifunctional squaramide multiple H-bond donor organocatalysts have been designed and synthesized by the rational assembly of chiral privileged scaffolds of indanol and cinchona alkaloids. In the presence of 1 mol % 1a, the asymmetric Michael addition reaction of 1,3-dicarbonyl compounds to nitroolefins proceeded to provide the product in high yields (up to 92%) and with good to high ee values (up to 96%). The additional H-bond in this squaramide system plays a crucial role in enhancing the enantioselectivity.     

Pyrrolidine-thiourea as a bifunctional organocatalyst: highly enantioselective Michael addition of cyclohexanone to nitroolefins

[reaction: see text] Asymmetric Michael additions of cyclohexanone to both aryl and alkyl nitroolefins in the presence of 20 mol % of organocatalyst 2b and 10 mol % of n-butyric acid afford adducts 5 with high diastereoselectivities and enantioselectivities.     

Enantioselective Michael addition of alpha-substituted cyanoacetates to vinyl ketones catalyzed by bifunctional organocatalysts

A highly enantioselective Michael addition of alpha-substituted cyanoacetates to vinyl ketones was accomplished in the presence of simple bifunctional thiourea/tertiary amine organocatalysts. A number of alpha-aryl or alkyl cyanoacetates have been successfully applied to give multifunctional compounds with an all-carbon-substituted quaternary stereocenter in excellent enantioselectivities (82-97 % ee) and yields (61-99 %). The optical pure adducts could be smoothly converted to variously structured beta(2,2)-amino acid esters. Moreover, an interesting reaction model involving multiple hydrogen-bonding interactions amongst the thiourea/tertiary amine catalyst and the reactants has been proposed based on the absolute configuration of the adduct and computational studies.