南开大学苏波团队报道了通过铜催化级联氢硼化和芳基环丙烷的氢胺化对映选择性1,4-硼酰胺化反应。相关研究成果于2024年11月13日发表在国际一流学术期刊《美国化学会杂志》。

在远端位置同时带有硼基和氨基的化合物，是合成药物、候选药物和天然产物的宝贵合成子，但它们的催化对映选择性合成仍然很少被探索。

该文中，研究人员报道了通过铜催化亚芳基环丙烷的级联氢硼酰化和氢胺化反应，进行的第一个对映选择性1,4-硼酰胺化反应。该反应以高度化学、位点和对映选择性的方式结合了四种现成的组分（>20:1 r.r.和高达99%ee），产生了各种有合成价值的对映体富集的4-氨基烷基硼酸酯。

它们在药物合成和药物发现中的多样化转化和广泛应用，显示了这些产品的多用途。初步的机理研究阐明了其高化学和位点选择性的操作反应途径、中间体和来源。

附：英文原文

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

Author: Yu-Shen Zhu, Ya-Lin Guo, Ying-Ying Zhu, Bo Su

Issue&Volume: November 13, 2024

Abstract: 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.

DOI: 10.1021/jacs.4c12852

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c12852