Cobalt-Catalyzed Regio-, Diastereo-, and Enantioselective Reductive Coupling of Internal Alkynes with Cyclobutenes

While low-valent cobalt complex-catalyzed asymmetric reductive coupling of alkynes with acceptor-substituted alkenes is well-established, the reactions with unactivated alkenes have not been reported. Herein, we reported the cobalt-catalyzed asymmetric ene-yne reductive coupling of internal alkynes and unactivated cyclobutenes. The reaction produced densely functionalized chiral vinyl cyclobutanes up to 92% yields with excellent absolute and relative stereocontrol (>99% ee, >20:1 dr, and >20:1 E/Z), and high >20:1 regioselectivity. The scaled-up reaction and the post-synthetic derivatizations further elucidated the efficiency of the designed protocol. The preliminary mechanistic investigations suggested the involvement of zinc-mediated low-valent cobalt(I) complex generation, oxidative ene-yne cyclization, and protonation as the key mechanistic steps.