Enantioselective reductive aryl-benzylation of alkenes by a nickel-titanium bimetallic system

The direct use of alcohols as coupling partners via homolytic C–OH bond cleavage remains a formidable challenge but holds great opportunities to achieve useful transformations. In this context, the use of free alcohols as precursors of carbon radicals in nickel-catalyzed asymmetric dicarbofunctionalization of tethered olefins is highly desirable. Reported herein is an asymmetric reductive aryl-benzylation of alkenes using free benzyl alcohols mediated by a nickel-titanium bimetallic system. The reaction affords the corresponding chiral benzene-fused cyclic compounds including oxindoles, dihydrobenzofurans, tetralins, indane, and isochroman bearing an all-carbon quaternary stereocenter with up to 99% enantiomeric excess. The practical utilities of the protocol are demonstrated in the late-stage modification of some scaffolds in pharmaceuticals and natural products. This study shows that the key to success is the merging of titanium-mediated direct homolysis of alcoholic C–O bonds with nickel-catalyzed asymmetric olefin difunctionalization.