Synthesis of C3-Substituted 1-Indenones Enabled by CuCl/Brønsted Acid Cooperative Catalysis

A cooperative CuCl/Brønsted acid catalytic system has been developed to enable divergent C3-functionalization of <i>o</i>-alkynylbenzaldehydes through a key <i>O-5-exo</i>-dig cyclization pathway. The resulting allylic carbocation intermediates can be efficiently intercepted by either styrenes or alcohols, affording 3-styryl-1-indenones and 3-alkoxy-1-indenones, respectively, with complete regioselectivity. The exocyclic styryl moiety serves as a synthetically versatile handle for late-stage diversification of indanocine-type scaffolds. This operationally simple method employs inexpensive CuCl as the sole metal catalyst under mild conditions, furnishing 35 examples in yields of up to 98%.