近日，印度CSIR中央药物研究所Ravindra Kumar团队研究了wolff重排有机催化三组分模块化合成BN同异构体和BN-2,1-偶氮杂萘。这一研究成果发表在2025年9月9日出版的《自然-化学》杂志上。

[2,1]-偶氮杂萘是萘中独特的硼氮（BN）同分异构体，它吸引了人们对开发具有增强治疗效能的分子的兴趣。现有的合成策略一般是条件苛刻的双组分反应。

研究组报道了一种有机催化的三组份模块化合成方法，该方法是通过Wolff重排在非张力环酮（n=4-8）展开环后，以环为主题合成BN-异构体和BN-2,1-偶氮杂萘。该策略以2-甲酰基硼酸为C-B替代物，TMSN₃为外源单氮源，通过在一次操作下锻造C-C、C-N和B-N键，可以重新快速合成BN异构体。

该方法适用于广泛的底物范围（58例），包括环酮类化合物和各种杂环化合物，可获得1C环扩展[2,1]-偶氮杂环化合物。该反应对无环酮也有效，生成BN萘同分酯。对照实验和密度泛函理论研究表明[1,2]-C-C / C-H移位后的反应路径与Wolff重排相似。

附：英文原文

Title: Organocatalysed three-component modular synthesis of BN isosteres and BN-2,1-azaboranaphthalenes via Wolff-type rearrangement

Author: Singh, Akansha, Kant, Ruchir, Grellier, Mary, Kumar, Ravindra

Issue&Volume: 2025-09-09

Abstract: [2,1]-Azaboranaphthalenes represent unique boron–nitrogen (BN) isosteres of naphthalenes, attracting interest for the development of molecules with enhanced therapeutic potency. The existing synthetic strategies are generally two-component reactions with harsh conditions. Here we report an organocatalysed three-component modular synthesis of ring-fused BN isosteres and BN-2,1-azaboranaphthalenes following ring expansion of unstrained cyclic ketones (n=4–8) via Wolff-type rearrangement. The strategy used 2-formylarylboronic acid as a C–B surrogate and TMSN3 as an exogenous single nitrogen source, allowing the de novo rapid synthesis of BN isosteres by forging C–C, C–N and B–N bonds under a single operation. The developed method proved to be compatible with a broad substrate scope (58 examples), including cyclic ketones and diverse heterocycles, which afforded 1C ring-expanded [2,1]-azaborines.The reaction was also effective with acyclic ketones, yielding BN naphthalene isosteres. Control experiments and density functional theory study dictate the plausible reaction pathways following [1,2]-C–C/C–H shift, analogous to Wolff rearrangement.

DOI: 10.1038/s41557-025-01938-1

Source: https://www.nature.com/articles/s41557-025-01938-1