Nickel-catalyzed enantioselective annulation/alkynylation and Sonogashira reaction to form C(sp3)-C(sp) and C(sp2)-C(sp) bonds, respectively

Abstract

While traditional Sonogashira reaction requires a palladium catalyst and a copper co-catalyst, some recent variants were reported being promoted by single transition metals. Here we report a single nickel-catalyzed tandem Heck-Sonogashira annulation/alkynylation for enantioselectively constructing C(sp3)-C(sp) bond. In addition, using the same catalytic system, Sonogashira C(sp2)-C(sp) cross-coupling has also been achieved. The alkynylations described in this report are important for the three reasons: 1. C(sp3)/(sp2)-C(sp) bonds exist in many bioactive natural products and drug molecules as well as their key synthetic intermediates; 2. There was no precedent for single nickel-catalyzed Sonogashira reaction owing to the difficulties caused by strong coordination of nickel to the triple bond to inactivate the catalyst; 3. Isolation and characterization of single-crystal structure of a resting state intermediate, di-phosphine chelated σ-alkyl-NiII-I complex, which provided crucial evidence to support the mechanistic postulation and guided DFT calculations.