Remote Double C(sp³)-H Bond Asymmetric Aminoboration of Unactivated Alkenes via Bimetallic Orthogonal Relay Catalysis

Catalytic remote C(sp³)-H bond functionalization via the "chain-walking" pathway has been recognized as a promising strategy for constructing diverse molecular frameworks. However, the accessible functionalization sites remain limited and predominantly focus on a single site, typically either the terminal position or a specific internal site of the carbon chain. Multisite C(sp³)-H bond functionalization, particularly in an asymmetric manner, remains a substantial challenge. Herein, we present a bimetallic orthogonal catalytic system comprising cobalt and copper catalysts paired with two distinct chiral ligands, which enables simultaneous double C(sp³)-H bond aminoboration at remote positions from the initial C-C double bond. This system features broad substrate scope and generality across a variety of counterparts with excellent regio- and enantioselectivity. The synthetic utility of this method is highlighted by the late-stage modification of natural products and drugs, as well as in the enantioselective synthesis of β-aminoalkylboronate directly from aryl alkane via sequential dehydrogenation of alkanes followed by our bimetallic catalysis, without isolation of intermediates. A series of experimental studies were conducted to elucidate the orthogonal feature of the two metal catalysts and the synergistic effect of the two chiral ligands in governing the "chain-walking" and the subsequent aminoboration process.