Nickel-Catalyzed Enantioselective Cyclizative Alkylation of 1,6-Enynes with Diazo Compounds and Alkyl Halides

Abstract Transition-metal-catalyzed cyclization of 1,n-enynes represents a versatile platform for the construction of structurally diverse chiral heterocycles. Despite substantial advances in this field, the enantioselective cyclizative alkylation of 1,n-enynes remains a formidable synthetic challenge, primarily due to the inherent difficulty in simultaneous control of regio-, chemo-, and stereoselectivity. Herein, we disclose a highly enantioselective cyclizative alkylation of 1,6-enynes employing two complementary alkylating reagents: diazo compounds and readily available alkyl iodides. This protocol proceeds under mild conditions and features broad substrate scope, delivering enantioenriched γ-lactams and pyrrolidine derivatives bearing quaternary stereogenic centers in good yields (up to 81%) and enantioselectivities (53 examples, up to 98% ee). Mechanistic studies corroborate that these two types of alkylating reagents follow entirely distinct catalytic pathways.