Silica gel supported pyrrolidine-based chiral ionic liquid as recyclable organocatalyst for asymmetric Michael addition to nitrostyrenes

A novel silica gel supported pyrrolidine-based chiral ionic liquid 6a has been developed and found to be a highly effective catalyst for the Michael addition reaction of ketones with nitrostyrenes. The reactions generated the corresponding products in good yields (up to 94%), excellent enantioselectivities (up to >99% ee), and high diastereoselectivities (up to >99:1 dr). In addition, the catalyst 6a can be reused at least five times without a significant loss of catalytic activity and stereoselectivity.     

Surfactant-type asymmetric organocatalyst: organocatalytic asymmetric Michael addition to nitrostyrenes in water

A surfactant-type asymmetric organocatalyst (STAO) catalyzed highly efficient Michael addition to nitroalkenes with high stereoselectivities in water without using any organic solvents or additional additives.     

A recyclable organocatalyst for asymmetric Michael addition of acetone to nitroolefins

Based on different chiral diamine skeletons, a series of bifunctional primary amine-thiophosphoramides were synthesized and screened as the catalysts for the asymmetric Michael addition of acetone to both aromatic and aliphatic nitroolefins. Under the catalysis of a thiophosphoramide derived from 1,2-diphenylethane-1,2-diamine, the corresponding adducts were obtained in high yields (up to >99%) with excellent enantioselectivities (97-99% ee) under mild reaction conditions. Moreover, the catalyst could be recovered via simple phase separation and reused at least five times without any loss of both catalytic activity and stereocontrol.     

Aromatic l-prolinamide-catalyzed asymmetric Michael addition of aldehydes to nitroalkenes

Two chiral aromatic l-prolinamides were synthesized in high overall yield (95%) from N-Boc-l-proline and served as organocatalysts in asymmetric Michael reactions of aldehydes to nitroalkenes. Under the optimized reaction conditions, (S)-N-tritylpyrrolidine-2-carboxamide 4 was found to be a highly efficient organocatalyst for the Michael addition, and the corresponding Michael adducts were obtained in good yields (up to 94%), with excellent enantioselectivities (up to 99% ee) and diastereoselectivities (up to 99:1 dr).     

Noncovalently supported heterogeneous chiral amine catalysts for asymmetric direct aldol and Michael addition reactions

A new strategy for the immobilization of asymmetric organocatalysts by combining polystyrene (PS)/sulfonic acids and chiral amines in situ through acid-base interactions is presented. The PS/sulfonic acids play a dual role as catalyst anchors and modulators for activity and stereoselectivity. Different types of polymeric sulfonic acids were examined and 1% divinylbenzene (DVB) cross-linked PS/sulfonic acid 1 e with a medium loading of sulfonic acid moieties was found to be the optimal support. Furthermore, the noncovalency of this system allows combinatorial screening of optimal catalysts for the targeted reactions. In this regard, highly efficient and enantioselective heterogeneous catalysts were identified for the asymmetric direct aldol and Michael addition reactions. The catalysts could be easily recovered by filtration and reused for six cycles with similar stereoselectivity but slightly decreased activity. Significantly, the deactivated catalysts could be regenerated following an acidic washing/amine recharging procedure.     

First organocatalyzed asymmetric Michael addition of aldehydes to vinyl sulfones

[reaction: see text] The first asymmetric direct Michael addition of aldehydes to vinyl sulfones catalyzed by N-iPr-2,2'-bipyrrolidine is described. 1,4-Adducts are obtained in good yields and enantioselectivities. The determination of absolute configuration allowed us to postulate a Si,Si transition state model, as shown previously for nitroolefins.     

Organocatalytic and direct asymmetric vinylogous Michael addition of alpha,alpha-dicyanoolefins to alpha,beta-unsaturated aldehydes

The first highly regio-, chemo-, diastereo- and enantioselective direct vinylogous Michael addition of alpha,alpha-dicyanoolefins to alpha,beta-unsaturated aldehydes is described, employing readily available chiral alpha,alpha-diarylprolinol salts as iminium organocatalysts.     

Novel polymer-supported chiral catalysts for the asymmetric addition of diethylzinc to aldehydes

Newly synthesized polymer-supported chiral amino alcohol catalysts 5a and 5b have been proved to be effective for the enantioselective addition of diethylzinc to aldehydes, affording the corresponding sec-alcohols in moderate enantiomeric excesses with good to excellent yields. The recycled catalyst could be reused in the same reaction without significant deterioration in performance.     

Asymmetric Michael addition reactions of aldehydes with nitrostyrenes catalyzed by functionalized chiral ionic liquids

A new class of pyrrolidine-based functionalized chiral ionic liquids (FCILs) has been developed and shown to be effective and reusable catalysts for the asymmetric Michael addition reactions. For the Michael addition reaction involving various aldehydes and nitrostyrenes, FCIL 6, in combination with trifluoroacetic acid as an additive, was found to be a very effective catalyst, compared to FCIL 3, which varied slightly in structure. Excellent yields (up to 99%), good enantioselectivities (up to 85% ee), and high diastereoselectivities (syn/anti ratio up to 97:3) were obtained for these reactions. The FCIL catalysts were easily recycled and reused for at least five times without significantly losing their ability to affect the outcome of the asymmetric reactions.     

Novel cyclic β-aminophosphonate derivatives as efficient organocatalysts for the asymmetric Michael addition reactions of ketones to nitrostyrenes

Three novel catalysts based upon cyclic β-aminophosphonate derivatives 1–3 were designed to catalyze the asymmetric Michael addition reactions of ketones to β-nitrostyrenes. Among the catalysts that have been prepared in this study, cyclic β-aminophosphonic acid monoethylester 3 showed the highest catalytic ability, giving the corresponding Michael adduct in good yields, high enantioselectivities (up to 92% ee), and high diastereoselectivities (syn:anti up to 95:5).     

Salicylaldehyde based oxazolidines as catalysts for the asymmetric addition of diethylzinc to aldehydes

A series of oxazolidines have been prepared by condensation of N‐isopropyl norephedrine with a variety of salicylaldehyde derivatives. Despite the stereochemical relationship of (1R,2S)‐norephedrine with (1R,2S)‐ephedrine, the resultant oxazolidines 12‐14 were determined to have a stronger stereochemical relationship with (1S,2S)‐pseudoephedrine based oxazolidines. The resultant oxazolidines were used as catalytic ligands in the addition of diethylzinc to several aldehydes. It was determined that the oxazolidine derivative 12 gave the highest yield and a moderate enantioselectivity.     

Isoleucine-catalyzed direct asymmetric aldol addition of enolizable aldehydes

Isoleucine-catalyzed direct enantioselective aldol additions between enolizable aldehydes are reported. Intermediate acetal structures dictate the configurative outcome and were supported by a hydrogen bond. This direct isoleucine-catalyzed aldol addition represents a welcome complement to both proline- and histidine-catalyzed aldol additions of enolizable aldehydes.     

Proline-based reduced dipeptides as recyclable and highly enantioselective organocatalysts for asymmetric Michael addition

A series of novel proline-based reduced dipeptides was developed and evaluated for a direct Michael addition of ketones and aldehydes to nitroalkenes. Excellent yields (up to 95%), diastereoselectivities (up to 98% dr) and enantioselectivities (up to 98% ee) were achieved in the presence of 5 mol% catalyst without any additional additives at room temperature.     

Organocatalytic asymmetric direct Michael addition of aromatic ketones to alkylidenemalononitriles

The asymmetric direct Michael addition of aromatic ketones to highly active alkylidenemalononitriles was investigated by employing a chiral primary amine 9-amino-9-deoxyepicinchonine. In general modest to good enantioselectivities (71–84% ee) could be obtained in acceptable isolated yields (48–85%) for an array of substrates.     

Antibody-catalyzed asymmetric intramolecular Michael addition of aldehydes and ketones to yield the disfavored cis-product

The development of new catalytic asymmetric reactions continues to be a major goal in organic chemistry. Here we report a novel antibody-catalyzed intramolecular Michael addition of aldehydes and ketones to enones. The reaction is enantioselective and diastereoselective with a high ee value and cis/trans ratio. This is the first example of asymmetric intramolecular Michael addition of ketones. Antibody 38C2 is the only catalyst to date capable of generating this selectivity in Michael addition products.     

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.     

Thiophosphoramide catalyzed asymmetric Michael addition of acetone to functionalized nitrostyrenes: a convenient approach to optically active tetrahydropyrans

Thiophosphoramide 5d was found to be an effective organocatalyst for the enantioselective Michael reaction of problematic acetone to various hydroxymethyl nitrostyrenes, affording the multisubstituted tetrahydropyrans with three stereogenic centers. The Michael addition products generated were obtained as a single diastereomer with enantioselectivities ranging from 46% to 74% ee.     

An efficient enantioselective method for asymmetric Michael addition of nitroalkanes to alpha,beta-unsaturated aldehydes

The addition of nitroalkanes to alpha,beta-unsaturated aldehydes under the catalysis of (S)-2-(diphenyl(trimethylsilyloxy)methyl)pyrrolidine and lithium acetate as additive afforded gamma-nitroaldehydes in good yield and up to 97% ee.