Asymmetric Alkynylation of Isoquinoline Iminium Salts

Significance

A highly enantioselective copper(I)-QUINAP complex catalyzed addition of terminal alkynes to alkylisoquinoliniums and dihydroisoquinoliniums in excellent yields and enantioselectivities is reported. Optimum results are achieved using copper acetylides, which may be generated in situ and are known to bind strongly to a number of chiral ligands. A polymer-supported approach also has been accomplished. The absolute configuration of products was established by comparison to that of (S)-(-)-homolaudanosine, an isoquinoline from a family of alkaloids with neurologic activity (A. J. Aladesamm et al. J. Nat. Prod. 1983, 46, 127-131), which was synthesized under the same conditions. Preliminary biological activity screening of obtained products indicates anti-yeast proliferation properties as a function of structure and absolute configuration.