Cobalt-Catalyzed Enantioselective Negishi Cross-Coupling of Racemic α-Bromo Esters with Arylzincs

The first cobalt-catalyzed enantioselective Negishi cross-coupling reaction, and the first arylation of alpha-halo esters with arylzinc halides, are disclosed. Employing a cobalt-bisoxazoline catalyst, various alpha-arylalkanoic esters were synthesized in excellent enantioselectivities and yields (up to 97% ee and 98% yield). A diverse range of functional groups, including ether, halide, thioether, silyl, amine, ester, acetal, amide, olefin and heteroaromatics is tolerated by this method. This method was suitable for gram-scale reactions, enabling the synthesis of (R)-xanthorrhizol with high enantiopurity. Radical clock experiments support the intermediacy of radicals.