Enantioselective, Copper-Catalyzed Alkynylation of Ketimines To Deliver Isoquinolines with α‑Diaryl Tetrasubstituted Stereocenters

An
enantioselective, copper-catalyzed alkynylation of cyclic α,α-diaryl
ketiminium ions has been developed to deliver isoquinoline products
with diaryl, tetrasubstituted stereocenters. The success of this reaction
relied on identification of Ph-PyBox as the optimal ligand, i-Pr2NEt as the base, and CHCl3 as
the solvent. A broad scope and functional group tolerance were observed.
Notably, the use of both aryl and silyl acetylenes results in high
yields and enantioselectivities. Mechanistic experiments are consistent
with a dimeric or higher order catalyst.