Enantioselective\n1,4-Borylamination via Copper-Catalyzed\nCascade Hydroborylation and Hydroamination of Arylidenecyclopropanes

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