Enantioselective 1,4-Borylamination via Copper-Catalyzed Cascade Hydroborylation and Hydroamination of Arylidenecyclopropanes

Compounds bearing both boryl and amino groups at distal positions are invaluable synthons for synthesizing pharmaceuticals, drug candidates, and natural products, but their catalytic enantioselective synthesis remains rarely explored. We report the first enantioselective 1,4-borylamination reaction through a copper-catalyzed cascade hydroborylation and hydroamination of arylidenecyclopropanes. This reaction combines four readily available components in a highly chemo-, site-, and enantioselective fashion (>20:1 r.r. and up to 99% ee), yielding a diverse array of synthetically valuable enantioenriched 4-amino alkylboronates. The versatile utility of these products is highlighted by their diverse transformations and wide applications in pharmaceutical synthesis and drug discovery. Preliminary mechanistic studies were conducted to elucidate the operative reaction pathway, intermediates, and origins of its high chemo- and site-selectivity.