A general organic catalyst for asymmetric addition of stabilized nucleophiles to acyl imines

Cinchona alkaloid-derived thiourea catalysts promote nucleophilic additions to acyl imines for the asymmetric synthesis of secondary amine adducts. The hydroquinine-derived thiourea catalyst efficiently promotes the aza-Henry reaction of nitroalkane with acyl imines, affording beta-nitroamines in good yields with enantioselectivities of 90-98% ee and diastereoselectivities up to 97%. The scope of the reaction also includes dimethyl malonate as a nucleophile to access beta-amino esters in high enantiopurity. Under the optimized reaction conditions, secondary amine adducts of high enantiopurity are generated based on various aromatic and alpha, beta-unsaturated acyl imines. (c) 2006 Elsevier Ltd. All rights reserved.