Enantioselective Copper-Catalyzed Quinoline Alkynylation

A highly enantioselective copper-catalyzed alkynylation of quinolinium salts is reported. The reaction employs StackPhos, a newly developed imidazole-based chiral biaryl P,N ligand, and copper bromide to effect a three-component reaction between a quinoline, a terminal alkyne, and ethyl chloroformate. Under the reaction conditions, the desired products are delivered in high yields with ee values of up to 98 %. The transformation tolerates a wide range of functional groups with respect to both the alkyne and the quinoline starting materials and the products are easily transformed into useful synthons. Efficient, enantioselective syntheses of the tetrahydroquinoline alkaloids (+)-galipinine, (+)-angustureine, and (-)-cuspareine are reported.