福州大学宋秋玲团队报道了铜催化烯烃与1,2-苯并氮杂硼化物不对称硼氢化制备手性萘异构体。相关研究成果于2024年4月8日发表在《自然—化学》。

生物同位置换已成为药物结构优化的一种明确策略。萘是许多手性药物和候选药物的核心组分。然而，作为一种很有前途的萘异对映体，1,2-苯并氮杂硼化物的手性形式由于缺乏有效的合成方法而很少被探索。

该文中，研究人员描述了铜催化的烯烃与1,2-苯并氮杂硼化物的对映选择性硼氢化反应。该方法为以高产率和优异的对映选择性构建具有2-碳生成中心，或烯骨架的各种手性1,2-苯并氮杂硼烷化合物（60多个实例），提供了一个通用的原子经济和有效的构建平台。

研究人员制备了三种具有生物活性的手性含萘分子的1,2-苯并氮硼化物类似物，并围绕手性1,2-苯并氮硼化物进行了一系列转化。值得注意的是，该研究的硼氢化过程表明，1,2-苯并氮硼化物的身份在速率决定步骤和催化剂静止状态中起着重要作用。

附：英文原文

Title: Copper-catalysed asymmetric hydroboration of alkenes with 1,2-benzazaborines to access chiral naphthalene isosteres

Author: Su, Wanlan, Zhu, Jide, Chen, Yu, Zhang, Xu, Qiu, Weihua, Yang, Kai, Yu, Peiyuan, Song, Qiuling

Issue&Volume: 2024-04-08

Abstract: Bioisosteric replacement has emerged as a clear strategy for drug-structure optimization. Naphthalene is the core element of many chiral pharmaceuticals and drug candidates. However, as a promising isostere of naphthalene, the chiral version of 1,2-benzazaborine has rarely been explored due to the lack of efficient synthetic methods. Here we describe a copper-catalysed enantioselective hydroboration of alkenes with 1,2-benzazaborines. The method provides a general platform for the atom-economic and efficient construction of diverse chiral 1,2-benzazaborine compounds (more than 60 examples) that bear a 2-carbon-stereogenic centre or allene skeleton in high yields and excellent enantioselectivities. Three 1,2-benzazaborine analogues of bioactive chiral naphthalene-containing molecules have been prepared, and a series of transformations around chiral 1,2-benzazaborines have also been developed. Notably, the hydroboration process of this study reveals that the identity of 1,2-benzazaborine plays an essential role in the rate-determining step and catalyst resting state.

DOI: 10.1038/s41557-024-01505-0

Source: https://www.nature.com/articles/s41557-024-01505-0