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).     

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%.     

Pyrrolidine-carbamate based new and efficient chiral organocatalyst for asymmetric Michael addition of ketones to nitroolefins

The novel ((S)-pyrrolidin-2-yl)methyl phenylcarbamate was synthesized and used as an efficient organocatalyst for the asymmetric Michael addition of cyclic/acyclic ketones to nitroolefins. Interestingly, the resulting Michael adducts were obtained in good to high yields (up to 96%) with excellent stereoselectivity (ee up to >99%, dr up to >99:1) without using any additive.     

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.     

Highly enantioselective Michael addition of cyclic ketones to chalcones catalyzed by pyrrolidine-based imides

An efficient procedure for asymmetric Michael addition reaction of cyclic ketones with low activated chalcones catalyzed by pyrrolidine-based phthalimide and 1,8-Naphthalimide catalysts was developed. The corresponding products were obtained in high yields with high diastereoselectivities (up to 99:1 dr) and high enantioselectivities (up to 96% ee) under mild conditions.     

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.     

Highly enantioselective Michael addition of isobutyraldehyde to nitroalkenes

The asymmetric catalytic Michael reaction between isobutyraldehyde and nitroalkanes with chiral primary amine thiourea organocatalysts was described. In the presence of 10 mol % of 1-((1R,2R)-2-amino-1,2-diphenylethyl)-3-benzylthiourea, the desired products were achieved in excellent enantioselectivity (up to>99% ee) with up to 98% yield.     

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.     

Magnetic nanoparticles supported cinchona alkaloids for asymmetric Michael addition reaction of 1,3-dicarbonyls and maleimides

New magnetically recoverable cinchona alkaloid organocatalysts have been successfully developed for the asymmetric Michael addition reaction of 1,3-dicarbonyls and maleimides.     

A practical asymmetric conjugate addition to cyclic enones with chiral bifunctional Ru amido catalysts

A practical asymmetric C-C bond formation to synthetically useful β-chiral cyclic ketones (>99% ee) using bifunctional chiral amido Ru catalysts under an S/C = 1000, the highest ratio achieved so far in the literature for this class of reactions, is described. The catalytic reactivity decreases in the order of Ru(Msdpen)(hmb) > Ru(Pfbsdpen)(hmb) > Ru(Tsdpen)(hmb) > Ru(PMsdpen)(hmb), where Ru(Pfbsdpen)(hmb) is a newly developed chiral bifunctional catalyst. Complex Ru(Msdpen)(hmb) was identified as the best in terms of reactivity and enantioface selectivity, whereas Ru(PMsdpen)(hmb) gave unsatisfactory results. An importance of the NH proton in the bifunctional catalyst for determining the enantioselectivity has been experimentally demonstrated. Valuable information for the reaction mechanism was accumulated.     

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.     

A highly efficient asymmetric Michael addition of anthrone to nitroalkenes with cinchona organocatalysts

A highly efficient asymmetric Michael addition of anthrone to nitroalkenes catalyzed by cinchona alkaloids was described. Up to 99% ee of the corresponding adduct was obtained.     

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.     

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.