Nickel-catalysed migratory hydroalkynylation and enantioselective hydroalkynylation of olefins with bromoalkynes

Xiaoli Jiang,You Wang,Shaolin Zhu,Mei Duan,Bo Han,Zhuofan Gui,Yuhang Xue

doi:10.1038/s41467-021-24094-9

Abstract

α-Chiral alkyne is a key structural element of many bioactive compounds, chemical probes, and functional materials, and is a valuable synthon in organic synthesis. Here we report a NiH-catalysed reductive migratory hydroalkynylation of olefins with bromoalkynes that delivers the corresponding benzylic alkynylation products in high yields with excellent regioselectivities. Catalytic enantioselective hydroalkynylation of styrenes has also been realized using a simple chiral PyrOx ligand. The obtained enantioenriched benzylic alkynes are versatile synthetic intermediates and can be readily transformed into synthetically useful chiral synthons.

Highlights

Α-Chiral alkyne is a key structural element of many bioactive compounds, chemical probes, and functional materials, and is a valuable synthon in organic synthesis
As a key structural element, chiral alkynes motifs bearing an α stereocentre are often found in many bioactive compounds, chemical probes, and functional materials (Fig. 1a)
It was determined that NiI2·xH2O and the bathocuproine ligand (L) could generate the desired migratory alkynylation product as a single regioisomer [rr > 99:1] in 82% yield

Summary

Introduction

Α-Chiral alkyne is a key structural element of many bioactive compounds, chemical probes, and functional materials, and is a valuable synthon in organic synthesis. 1234567890():,; As a key structural element, chiral alkynes motifs bearing an α stereocentre are often found in many bioactive compounds, chemical probes, and functional materials (Fig. 1a). They are valuable synthons as the sp3-hybridized carbons could undergo versatile transformations to deliver useful sp2- or sp3-hybridized carbons[1]. Efficient strategies for catalytic, enantioselective C(sp3)–C(sp) coupling to generate such stereocentres have long been sought a Representative bioactive molecules bearing a chiral alkyne motif. As a continued development of general alternatives for asymmetric C(sp3)–C(sp) coupling, here we report an appealing approach via metalhydride[13,14,15] catalyzed asymmetric (remote) hydroalkynylation[16] from readily available alkene starting materials

Methods

Results

Conclusion