General, Catalytic Asymmetric Reductive Alkynylation of Tertiary Aliphatic and Aromatic Amides by Cooperative Catalysis With Iridium/Copper/Carreira's PINAP

Chiral propargylamines are a class of versatile building blocks in organic synthesis. Despite the recent breakthroughs on the catalytic asymmetric reductive alkynylation of amides to access propargylamines, a general protocol amenable to both aromatic and aliphatic tertiary amides remains elusive. Herein, we report that our recently developed methodology for the catalytic asymmetric reductive alkynylation of tertiary aliphatic amides can be extended to tertiary aromatic amides. Employing Vaska's complex/CuI/Carreira's (R,P)-PINAP ligand as the catalytic system and 1,1,3,3-tetramethyl-disiloxane (TMDS) as the hydrosilylation reagent, the method highlights good reagent economy and/ or excellent asymmetric induction as compared to the known ones. Moreover, the reductive alkynylation of tertiary aliphatic amides has been extended to a series of functionalized alkynes. It is expectable that the versatility, excellent functional group tolerance, and chemoselectivity of the method lay the foundation for diverse applications in organic synthesis and medicinal chemistry.