Mechanistic study of asymmetric Michael addition of malonates to enones catalyzed by a primary amino acid lithium salt

A mechanistic study was carried out for the asymmetric Michael addition reaction of malonates to enones catalyzed by a primary amino acid lithium salt to elucidate the origin of the asymmetric induction. A primary beta-amino acid salt catalyst, O-TBDPS beta-homoserine lithium salt, exhibited much higher enantioselectivity than that achieved with the corresponding catalysts derived from alpha- and gamma-amino acids for this reaction. Detailed studies of the transition states with DFT calculations revealed that the lithium cation and carboxylate group of the beta-amino acid salt catalyst have important roles in achieving high enantioselectivity in the Michael addition reaction of malonates to enones. (C) 2013 Elsevier Ltd. All rights reserved