Bifunctional Thiourea-Based Organocatalysts for Asymmetric C-C Bond Formation Reactions: Strecker, Nitro-Michael, Mannich

Abstract

A variety of new thiourea-based organocatalysts were synthesized and tested on different important C-C bond forming reactions: Strecker-reaction, Michael-addition, and Mannich-reaction. The Strecker reaction of hydrogen cyanide with aldimines was employed to determine the catalytic activity of the pyridyl thiourea derivatives and thus their potential as bifunctional organocatalysts. It was shown that incorporation of the imidazolyl moiety in place of a pyridyl group results in a new thiourea derivative that displays a much higher catalytic activity. The Michael-addition of acetone to aromatic nitroolefins in the presence of novel thiourea-based bifunctional organocatalysts gave high enantioselectivities up to 92% ee. The transition state geometries for the formation of R and S enantiomers in this Michael-addition reaction have been calculated and analyzed. The theoretical and experimental enantiomeric excess values show good agreement. Furthermore a highly enantioselective up to >99% ee direct Mannich-type reaction of different ketones with α-hydrazonoesters promoted by a chiral primary amine-thiourea catalysts is described.