Enantioselective 1,4-Borylamination Enabled by Copper Catalysis

Abstract Compounds bearing both boryl and amino groups are highly valuable synthons in organic synthesis. However, while enantioselective 1,1- and 1,2-borylamination reactions have been developed, processes enabling distal borylamination have rarely been investigated. Here, we present an enantioselective 1,4-borylamination reaction, achieved through a copper-catalyzed cascade hydroborylation and hydroamination of arylidenecyclopropanes. This four-component reaction provides direct access to enantioenriched 4-aminoalkylboronate products with high chemo-, site-, and enantioselectivity. The versatility of these products was demonstrated through their broad transformations and extensive applications in the synthesis of various drug core structures. Additionally, preliminary mechanistic studies were conducted to investigate the reaction pathway, intermediates, and high chemo- and site-selectivity.