Enantioselective C–C cross-coupling of unactivated alkenes

Abstract

Metal-catalysed cross-coupling has played a central role in modern chemical synthesis for decades. Unactivated alkenes, including light olefins, are manufactured on enormous scale in the petroleum industry and represent ideal starting materials for the preparation of pharmaceuticals, agrochemicals and materials. However, enantioselective cross-coupling of unactivated alkenes remains a challenging and long-standing goal. Here we report a highly enantio- and regioselective three-component cross-coupling of unactivated alkenes with aryl (or alkenyl) triflates and organometallics (or reductant) to construct diverse C sp3 stereocentres by nickel catalysis. Specifically, selective carbonickelation and in situ trapping with nucleophiles enable efficient hydrofunctionalization and dicarbofunctionalization of unactivated alkenes in a directing group-free manner. Nickel catalysts bearing bulky C2-symmetric chiral N-heterocyclic carbene ligands were crucial for attaining high reactivity and selectivity. This strategy offers a general, modular and divergent platform for rapidly upgrading feedstock alkenes to various value-added molecules and is expected to inspire the development of other challenging enantioselective alkene cross-couplings. Enantioselective C–C cross-coupling of unactivated alkenes is challenging. Now, nickel catalysts bearing bulky C2-symmetric chiral N-heterocyclic carbene ligands enable directing group-free asymmetric cross-coupling of unactivated alkenes with aryl or alkenyl triflates and nucleophiles, generating C sp3 stereocentres.