Regioselective Intermolecular Hydroamination of Unactivated Alkenes: “Co–H” Enabled Remote Functionalization

Abstract

The Co–H-catalyzed intermolecular hydroamination of unactivated alkenes with various amine electrophiles was achieved by introducing a removable directing group. The catalytic system, consisting of inexpensive Co(OAc)2·4H2O (10 mol %) and PhSiH3, features substrate-dependent regioselectivity, broad substrate scope (57 examples), and the avoidance of additives or an extra ligand. This transformation can smoothly accommodate a wide range of β,γ-unsaturated alkenes, γ,δ-unsaturated alkenes, and even challenging remote alkenes, providing a general and flexible protocol for the preparation of various β-, γ-, δ-, ε-, ζ-, and η-amino acid derivatives. The utility of this method was further demonstrated by the large-scale reaction and late-stage modification of drug molecules. Furthermore, a plausible mechanism was proposed and supported by a series of control experiments and radial clock experiments.