Palladium-Catalyzed Enantioselective Cyclization of 1,6-Enynes to Access Chiral γ-Butyrolactam

Abstract

A palladium-catalyzed asymmetric chlorocyclization of 1,6-enynes has been described. Controlling the chloride ion concentration in the system by substrate design is the key to achieving asymmetric chlorinated cyclization. In the presence of Pd(PhCN)₂Cl₂ and chiral phosphoramidite ligands, the reaction accesses diverse chiral (E)-α-chloromethylene-γ-butyrolactams with excellent E selectivity and enantioselectivity. The strategy features simple operations and mild conditions, offering a practical and reliable route for the synthesis of chiral butyrolactam compounds.