Pinacolborane-Enabled Low-Valent Cobalt Catalysis for Enantioselective [2 + 2 + 2] Cycloaddition of Enediynes

An enantioselective cobalt-catalyzed [2 + 2 + 2] cycloaddition of enediynes has been developed employing Co(acac)2 and (R)-binap activated by pinacolborane (HBpin). This reaction converts a wide range of enediynes into chiral tricyclic cyclohexadienes in high yields with excellent enantioselectivities (up to 99% ee). The cyclohexadiene products can undergo stereospecific Pd-catalyzed hydrogenation to afford chiral cyclohexanes bearing five continuous stereogenic carbon centers with high diastereoselectivity (dr >19:1). Mechanistic studies support a diyne-initiated cobalt(I)-mediated cycloaddition pathway.