英国曼彻斯特大学D. Leonori团队报道了叠氮化合物选择性C-H硼化反应的基本方法。相关研究成果于2021年5月20日发表在国际顶尖学术期刊《自然》。

硼官能团通常被引入取代芳香族碳氢键，并通过分子碎片的偶联加速小分子多样化。目前基于过渡金属催化C–H活化的方法对许多（杂）芳香族衍生物的硼酰化是有效的，但对叠氮类、含氮芳香杂环以及许多医药和农药产品的关键成分的适用性很小。

该文中，研究人员报告了一种使用稳定且廉价的胺-硼烷试剂的硼酰化策略。光催化作用将这些低分子量材料转化为可有效地添加到叠氮构建单元中的高反应性硼基化合物。该反应为sp2碳-硼键组装提供了一种机械上的替代策略，其中过渡金属介导的C–H活化和叠氮有机金属中间体的还原消除的基本步骤被直接的、小分子式的自由基加成取代。

胺-硼基自由基具有很强的亲核特性，这是关键特性，它可以通过靶向嗪最活跃的位点（包括靠近碱性N原子具有挑战性的位点）来实现可预测的和位点选择性的碳-硼键形成。该方法可以获得目前C-H活化策略难以获得的芳香位点，并导致硼化材料，否则很难制备。

该方法已应用于将胺-硼烷官能团引入复杂和工业相关的产品中。通过主流的交叉偶联技术，硼酰化叠氮产品的多样化确立了芳香氨基硼烷作为化学合成的一个强大的组成部分。

附：英文原文

Title: A radical approach for the selective C–H borylation of azines

Author: Ji Hye Kim, T. Constantin, M. Simonetti, J. Llaveria, N. S. Sheikh, D. Leonori

Issue&Volume: 2021-05-20

Abstract: Boron functional groups are often introduced in place of aromatic carbon–hydrogen bonds to expedite small-molecule diversification through coupling of molecular fragments1–3. Current approaches based on transition metal-catalysed C–H activation are effective for the borylation of many (hetero)aromatic derivatives4,5 but show narrow applicability to azines, N-containing aromatic heterocycles and key components of many pharmaceutical and agrochemical products.6 Here, we report an azine borylation strategy using stable and inexpensive amine-borane7 reagents. Photocatalysis converts these low molecular weight materials into highly reactive boryl radicals8 that undergo efficient addition to azine building blocks. This reactivity provides a mechanistically alternative tactic for sp2 carbon–boron bond assembly where the elementary steps of transition-metal mediated C–H activation and reductive elimination from azine-organometallic intermediates are replaced with a direct, Minisci9-style, radical addition. The strong nucleophilic character of the amine-boryl radicals is the key feature enabling predictable and site-selective carbon–boron bond formation by targeting the azine’s most activated position, including the challenging sites adjacent to the basic N-atom. This approach enables access to aromatic sites currently elusive to C–H activation strategies and has led to borylated materials that would otherwise be difficult to prepare. The process has been applied to the introduction of amine-borane functionalities onto complex and industrially-relevant products. The diversification of the borylated azine products by mainstream cross-coupling technologies establishes aromatic amino-boranes as a powerful class of building blocks for chemical synthesis.

DOI: 10.1038/s41586-021-03637-6

Source: https://www.nature.com/articles/s41586-021-03637-6