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).     

Polystyrene-immobilized pyrrolidine as a highly stereoselective and recyclable organocatalyst for asymmetric Michael addition of cyclohexanone to nitroolefins

Polystyrene-immobilized pyrrolidine 4 has been developed as a highly efficient, reusable, and stereoselective organocatalyst for the asymmetric Michael addition of cyclohexanone to nitroolefins. In the presence of trifluoroacetic acid, 4 catalyzed the reaction of cyclohexanone to a variety of nitroolefins with high yields (up to >99%) and excellent diastereoselectivities (up to >99:1 dr), and enantioselectivities (up to >99% ee). Furthermore, 4 could be recovered and recycled by a simple filtration of the reaction solution and used for more than 10 consecutive trials without significant loss of its catalytic activity.     

A new type of organocatalyst for highly stereoselective Michael addition of ketones to nitroolefins on water

(S)-2-((Naphthalen-2-ylsulfonyl)methyl)pyrrolidine, prepared in three steps from (S)-N-Boc-2-[((4-toluenesulfonyl)oxy)methyl]pyrrolidine in 62% overall yield, was used as a new type of organocatalyst bearing a pyrrolidine and a sulfone moiety. It shows very high catalytic activity toward the direct asymmetric Michael reaction of cyclohexanone and nitroolefins. All the corresponding adducts can be furnished in 90-99% yields and with up to 98% ee and over 99:1 dr on water in the presence of this catalyst (15 mol %) without any additive.     

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.     

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.     

一种新型双亲性有机小分子催化剂在水相体系中催化环己酮与硝基烯烃直接不对称Michael加成反应

设计合成了一系列基于脯氨酸巯基咪唑衍生物的新型双亲性有机小分子催化剂,在水相中加入酸作为助催化剂,可以高效高选择性的催化环己酮与硝基烯烃的不对称Michael加成反应,非对映选择性和对映选择性分别高达99：1和96%.     

Highly efficient organocatalytic asymmetric Michael addition of homoserine lactone derived cyclic imino esters to nitroolefins

An efficient stereoselective Michael addition reaction of homoserine lactone derived cyclic imino esters to nitroolefins promoted by a bis(cinchona alkaloid) (DHQD)₂AQN was achieved. This catalytic system features a wide substrate scope, furnishing the corresponding products with excellent diastereoselectivity (>95:5 dr) and good enantioselectivity (up to 87% ee) under mild conditions, and the Michael adducts could be easily transformed into highly functionalized spirocyclic γ-butyrolactone-pyrrolidines through a sequential nitro-Mannich reaction.     

Highly efficient and enantioselective Michael addition of acetylacetone to nitroolefins catalyzed by chiral bifunctional organocatalyst bearing multiple hydrogen-bonding donors

A new efficient catalyst system for the asymmetric addition of acetylacetone to nitroolefins using a chiral bifunctional organocatalyst bearing multiple hydrogen-bonding donors was developed. When using the organocatalyst 2c derived from natural cinchona alkaloid in optimal conditions, up to 98% chemical yield and 98% ee were observed with a variety of aromatic nitroolefins.     

Phosphinoyl-aziridines as a new class of chiral catalysts for enantioselective Michael addition

A series of new optically pure phosphine oxides containing chiral aziridine subunit were synthesized in good yields and applied as organocatalysts in asymmetric Michael reaction of various aliphatic aldehydes with β-nitrostyrene. The corresponding organocatalysts were synthesized starting from optically pure aziridines in a few simple efficient steps. The appropriate Michael adducts were obtained in most cases in very high chemical yield (up to 97%), excellent enantioselectivity (up to 98% of ee) and diastereoselectivity (up to 95:5 of dr).     

Recyclable cinchona alkaloid catalyzed asymmetric Michael addition reaction

A highly enantioselective and diastereoselective Michael addition reaction of α-fluoro-β-ketoesters with maleimides is catalyzed by fluorous cinchona alkaloid to afford two adjacent chiral centers. The catalyst attached with a perfluroalkyl tag can be recovered by fluorous solid-phase extraction (F-SPE).     

A new kind of organophosphorus compounds as an efficient catalyst for asymmetric C-C bond formation reactions

A new class of chiral pyrrolidine-phosphite organocatalysts, available from commercially starting materials, has been synthesized and shown to be good catalytic activity for asymmetric Michael and Aldol reactions. The reactions proceeded to give the products in good yield and in a highly selective manner. Ionic liquid [Bmim][BF₄] as an efficient green solvent has been employed in the Michael addition.     

Organocatalytic asymmetric conjugate addition of thioacetic acid to β-nitrostyrenes

A method for organocatalytic, enantioselective Michael addition reactions of thioacetic acid with a range of trans-β-nitrostyrenes has been developed. The processes, promoted by the chiral amine thiourea organocatalyst, take place in high yields with up to 70% ee.     

Ionic-liquid-supported organocatalyst for the enantioselective Michael addition of ketones to nitroolefins

Ionic-liquid-supported triazole-pyrrolidine 2, for the direct asymmetric Michael reaction was successfully synthesized. The supported catalyst demonstrated good activity and high enantioselectivity in the addition of cyclohexanone to nitroolefins. Furthermore, the supported catalyst can be readily recovered and reused four times without significant loss of catalytic activity.     

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.     

The preparation of novel chiral auxiliaries SAMIQ/RAMIQ and their application in the asymmetric Michael addition

A pair of novel chiral auxiliaries SAMIQ/RAMIQ was synthesized from l- or d-phenylalanine methyl ester hydrochloride over six steps in 45.8% and 44.4% yield, respectively. The SAMIQ-/RAMIQ-hydrazone methodology was applied for the asymmetric Michael addition of ketones to α,β-unsaturated carboxylic acid methyl esters, which afforded 3-substituted-5-oxo-alkanoates in moderate to good yield (65–82%) with excellent enantioselectivity (ee=95.3%∼>99.5%).     

Highly efficient asymmetric Michael addition of aldehydes to nitroalkenes with 4,5-methano-l-proline as organocatalysts

The 4,5-methano-l-prolines were used as chiral organocatalysts in asymmetric Michael addition of aldehydes to nitroolefins. These proline-like catalysts are unique for their rigid bicyclic structure with a cyclopropane and two H atoms attached to the bridgehead C atoms lying on the same side of the ring. They therefore showed high efficiency in asymmetric Michael addition of aldehydes to nitroolefins. Under the optimal conditions, excellent diastereo- and enantioselectivities (up to 97/3 dr and 98% ee) were obtained in high yields for a series of aldehydes and nitroolefins using only 5 mol % catalyst loading. The methodology features easily available catalysts, high catalytic efficiency and environmentally friendly procedures.     

Application of (S)- and (R)-methyl pyroglutamates as inexpensive, yet highly efficient chiral auxiliaries in the asymmetric Michael addition reactions

Methyl N-(E-enoyl)pyroglutamates, derived from inexpensive and readily available in both enantiomeric forms pyroglutamic acid were found to be an efficient Michael acceptors in the addition reactions with nucleophilic glycine equivalent allowing for an efficient practical asymmetric synthesis of β-substituted pyroglutamic acids and related compounds.