Ni-Catalyzed Enantioselective Intramolecular Mizoroki-Heck Reaction for the Synthesis of Phenanthridinone Derivatives

A Ni-catalyzed enantioselectiveintramolecular Mizoroki-Heckreaction has been developed to transform symmetrical 1,4-cyclohexadieneswith attached aryl halides into phenanthridinone analogues containingquaternary stereocenters. Herein, we report important advances inreaction optimization enabling control of unwanted proto-dehalogenationand alkene reduction side products. Moreover, this approach providesdirect access to six-membered ring heterocyclic systems bearing all-carbonquaternary stereocenters, which have been much more challenging toform enantioselectively with nickel-catalyzed Heck reactions. A widerange of substrates were demonstrated to work in good to excellentyields. Good enantioselectivity was demonstrated using a new synthesizedchiral iQuinox-type bidentate ligand (L27). The sustainability, low price of nickel catalysts, and significantlyfaster reaction rate (1 h) versus that of a recently reported palladium-catalyzedreaction (20 h) make this process an attractive alternative.