Enantioselective Divergent Cyclization of Amide‐Type 1,6‐Enynes Enabled by H–[Pd]–CN Catalysis

Abstract Enantioselective cyclization of 1,6‐enynes has been extensively developed as it offers an effective way to obtain chiral cyclic compounds. Herein, we report a divergent palladium‐catalyzed enantioselective cyclization of N ‐allyl‐substituted propiolamides, which allows for the efficient synthesis of chiral γ ‐lactams bearing a quaternary stereogenic center. Three distinctive cyclization strategies, namely, hydrocyanative cyclization, cyclization/Heck reaction, and cyclization/Heck/hydrocyanation, were successfully developed. The product can be selected by using different initial substrates under the same catalytic conditions or by fine‐tuning the reaction conditions for the same initial substrate. This catalytic system boasts broad substrate scope and wide functional‐group compatibility, where a diverse range of substituents on the aryl group and amide nitrogen atom were tolerated. The combination of experimental studies and theoretical calculations revealed the fundamental role of the ligand in regioselectivity and the role of H 2 O in the sequential cyclization/Heck/hydrocyanation reactions. H 2 O can lower the energy barrier of the reductive elimination step, thus promoting the reaction toward the target product formation.