Synthesis of highly decorated chiral 2-nitro-cyclohexane carboxylic esters through microwave-assisted organocatalyzed cascade reactions

Starting from (E)-beta-substituted-beta-nitroacrylates and alpha,beta-unsaturated ketones, a stereoselective organo-catalyzed one-pot methodology allowed to synthesize highly decorated chiral 2-nitro-cyclohexane carboxylic esters. The reaction is promoted by Cinchona alkaloid-derived primary amines in the presence of an acidic co-catalyst and affords two diastereoisomers, in good yields and high enantiomeric excess (often higher than 90% ee). By replacing conventional heating with microwave irradiation, cleaner reactions in shortened times (from 48 h to 30 min) were obtained, with improved dr (80:20) and high ee (up to 94%). The application of microwave technology to this organocatalytic methodology allowed also employing Cl substituted enones, leading to cyclohexanones with four contiguous stereocenters in two isomers only, and up to 99% enantioselectivity.