Ni/Chiral Sodium Carboxylate Dual Catalyzed Asymmetric O-Propargylation

A highly enantioselective O-propargylation catalyzed by combining a phosphine-nickel complex and an axially chiral sodium dicarboxylate has been developed. The transformation features mild reaction conditions, a broad substrate scope, and excellent functional group tolerance, offering an efficient approach to an array of enantioenriched O-propargyl hydroxylamines. Mechanistic studies support the presumed role of the chiral carboxylate as a counterion for nickel catalysis enabling the discovery of highly stereoselective transformations. The power of this reaction is illustrated by its application in the asymmetric total synthesis of potent firefly luciferase inhibitors and (S)-dihydroyashabushiketol.

Automated summary

The highly enantioselective O-propargylation catalyzed by combining a phosphine-nickel complex and an axially chiral sodium dicarboxylate offers a mild reaction conditions, broad substrate scope, and excellent functional group tolerance, leading to efficient synthesis of an array of enantioenriched compounds. The mechanistic studies support the role of the chiral carboxylate as a counterion for nickel catalysis, enabling the discovery of highly stereoselective transformations, showcasing its power in the asymmetric total synthesis of potent firefly luciferase inhibitors and (S)-dihydroyashabushiketol.