Switching Regioselectivity in the Asymmetric Bromocyclization of Difluoroalkenes Catalyzed by a Chiral Bisphosphine Oxide

Abstract

We present an efficient approach for the enantioselective synthesis of difluoromethylene-containing oxazine compounds through 6-endo-selective bromocyclization of difluoroalkenes using a chiral proton-bridged bisphosphine oxide complex (POHOP) as a catalyst precursor. The regioselectivity is significantly influenced by the solvent and the catalyst structure, and 6-endo cyclization products can be obtained preferentially with moderate to high enantioselectivity. This protocol offers complementary regioselectivity to our previously reported 5-exo-selective reaction, enabling synthesis of diverse medicinally interesting compounds.