Highly Enantioselective Synthesis of α-Amino Acid Derivatives by an NHC-Catalyzed Iutermolecular Stetter Reaction

摘要

α-Amino acids are one of the most important classes of compounds in nature and synthetic chemistry, and, consequently, many approaches have been developed for the synthesis of enantioenriched α-amino acids.Among these synthetic routes, a particularly versatile and challenging method to set up the chirality at the a position of α-amino acids is the formation of a transient enolate through a Michael addition followed by a stereoselective protonation. Enantioselective protonation is important in many biosynthetic sequences, and the development of powerful catalytic processes remains an ongoing challenge. Many different approaches for catalyzed enantioselective protonations have been realized; however, the combination of a conjugate addition with the asymmetric protonation of a transiently formed enolate stands out as being especially efficient and atom economic. In the context of α-amino acid synthesis, this strategy was first explored by Pracejus et al. in 1977 for the synthesis of cysteine derivatives with moderate enantio-selectivities (up to 54% ee) by using methyl 2-phthalimidoa-crylate as the Michael acceptor and cinchona alkaloids as the chiral catalysts. More recently, asymmetric approaches based on the use of organocatalysts or metal-based catalysts have shown improved selectivities, but the scope has remained limited.