Enantioselective and diastereoselective Michael addition of ketone/aldehyde to trans‐nitroolefins catalyzed by a novel chiral pyrrolidine‐thiourea

Abstract

The direct Michael addition reaction of cyclohexanone/aliphatic aldehydes with nitroolefins, catalyzed by a novel chiral pyrrolidine-thiourea catalyst 1a, is described. The desired 1,4-adducts were obtained in moderate yields with enantioselectivities up to 99% ee and dr up to 99:1 of the syn product.

A novel chiral aliphatic–aromatic diamine promoted direct, highly enantio‐ and diastereoselective Michael addition of cyclohexanone to nitroolefins under solvent‐free conditions

“…Strong electron withdrawing group nitro attached to benzene ring slightly lowered diasteroselectivetity and enantioselectivity (Table 3, entry 11). Naphthyl and heterocyclic nitroolefins also gave the corresponding products with good to excellent steroselectivities in high yields (Table 3, entries [12][13][14]. Moreover, alkenyl substituted nitroolefin can also be employed successfully; the same good diastereo-and enantioselectivity were observed as those found in the aryl substituted ones (Table 3, entry 15).…”

“…Compounds reported in Table 2 are all known in the literatures. 14,16,17,32,51 (S)-2-((R)-2-Nitro-1-phenylethyl)cyclohexanone (18a). …”

“…32 (S)-2,6-Diisopropyl-N-(pyrrolidin-2-ylmethyl)aniline (5). (S)-N-(2,6-diisopropyl-phenyl) pyrrolidine-2-carboxamide (14) was synthesized from L-proline, according to the known methods, 46,48 which was directly subjected to the next step without further purification.…”

“…[10][11][12] Among the variants of asymmetric conjugate additions, 13 nitroolefin-dependent Michael reactions are of special interest as these processes are the vital steps in the formations of amine, nitrile oxide, ketone, carboxylic acid, etc., which are recognized as synthetically interesting compounds. 14,15 In recent years, a great deal of effort has gone into the optimization of the structure of the chiral catalyst so as to achieve excellent selectivity and catalytic activity. [16][17][18][19][20][21][22][23][24][25][26] Of the developed organocatalysts in asymmetric catalysis, chiral diamines [27][28][29][30][31][32][33][34][35] derived from natural amino acids and cinchona alkaloids, which contain primary-secondary, primary-tertiary, secondary-secondary, and secondary-tertiary diamine catalysts, have proven to be powerful and been applied successfully to asymmetric catalytic Michael additions.…”

An Ionic Liquid Containing L‐Proline Moiety as Highly Efficient and Recyclable Chiral Organocatalyst for Michael Addition

“…Early in 2001, the first example of enantioselective Michael addition of cyclohexanone to β‐nitrostyrene catalyzed by L‐proline was reported by List et al . Since then, this reaction has always been taken as a model to explore more efficient organocatalysts . Among the catalysts, proline and pyrrolidine‐based derivatives were used as effective chiral catalysts for the Michael addition of aldehydes and ketones to nitroolefins .…”