Noncovalent interaction-driven regio- and enantioselective hydroalkynylation of unactivated alkenes to access remote chiral nitriles.

Abstract

Unactivated alkenes represent a challenging substrate for selective functionalization, particularly in achieving both regioselectivity and enantioselectivity. In this study, we present a strategy for the regio- and enantioselective hydroalkynylation of unactivated alkenes through the integration of noncovalent π⋯π interactions between the cyano group of the substrate and a chiral bis(oxazoline) ligand. The weak π⋯π interaction was supported by control experiments and computational studies. The method provides a reliable approach for synthesizing chiral nitriles with remote (β-, γ-, and δ-) stereocenters, which exhibit orthogonal reactivities and serve as valuable intermediates for further derivatization into otherwise difficult-to-access compounds. Our work provides a strategy for olefin functionalization and opens up avenues for the selective synthesis of chiral nitriles with remote stereocenters.