A Ni-catalyzed enantioselective
intramolecular Mizoroki–Heck
reaction has been developed to transform symmetrical 1,4-cyclohexadienes
with attached aryl halides into phenanthridinone analogues containing
quaternary stereocenters. Herein, we report important advances in
reaction optimization enabling control of unwanted proto-dehalogenation
and alkene reduction side products. Moreover, this approach provides
direct access to six-membered ring heterocyclic systems bearing all-carbon
quaternary stereocenters, which have been much more challenging to
form enantioselectively with nickel-catalyzed Heck reactions. A wide
range of substrates were demonstrated to work in good to excellent
yields. Good enantioselectivity was demonstrated using a new synthesized
chiraliQuinox-type bidentate ligand (L27). The sustainability, low price of nickel catalysts, and significantly
faster reaction rate (1 h) versus that of a recently reported palladium-catalyzed
reaction (20 h) make this process an attractive alternative.