Palladium-Catalyzed Enantioselective Tandem Phosphinolation/Cyclization of ortho-Alkynylbenzaldehydes and H-Phosphine Oxides: Access to C1-Phosphinoylated 1H-Isochromenes

A novel and effective method for the synthesis of chiral C1-phosphinoylated 1H-isochromenes has been developed. The reaction proceeds via a tandem asymmetric addition/cyclization under a catalytic system of Pd(OAc)2, a Josiphos-based ligand L9, and ZnCl2 in MeCN at 70 °C. This method demonstrates a broad substrate scope (27 examples), delivering excellent yields (up to 92%) and enantioselectivities (up to 95%).