Pd/GF-Phos-Catalyzed Asymmetric Three-Component Coupling Reaction to Access Chiral Diarylmethyl Alkynes
Guofeng Zhao, Yi Wu, Haihong Wu, Junfeng Yang, Junliang Zhang
Abstract
Significant attention has been given in the past few years to the selective transformations of N-tosylhydrazones to various useful compounds. However, the development of enantioselective versions poses considerable challenges. Herein we report a Pd-catalyzed enantioselective three-component coupling of N-tosylhydrazone, aryl halide, and terminal alkyne under mild conditions utilizing a novel chiral sulfinamide phosphine ligand (GF-Phos), which provides a facile access to chiral diarylmethyl alkynes, which are useful synthons in organic synthesis as well as exist as the skeleton in many bioactive molecules. A pair of enantiomers of the product could be easily prepared using the same chiral ligand by simply changing the aryl substituents of the N-tosylhydrazone and aryl halide. The salient features of this reaction include the readily available starting materials, general substrate scope, high enantioselectivity, ease of scale-up, mild reaction conditions, and versatile transformations.