Modular Synthesis of 1,2-Azaborines via Boron-mediated Strain-release Reductive Cyclization

摘要：1，2-氮杂硼作为一类新兴的芳香化合物生物等位体，具有广泛的应用前景。 在药物发现方面受到越来越多的关注。然而，目前1，2-二氢呋喃的合成 氮硼化合物遇到了很大的困难，包括如何获得多取代的1，2- 氮硼烷和氮杂芳烃，如何避免使用昂贵的催化剂和处理 敏感中间体，如何增加模块化和可扩展性等。在这里，我们建议 开发一种硼介导的应变释放还原环化(BSRC)策略来解决这些问题 可获得性和实用性挑战。在拟议的资助期内，我们的目标是 建立了合成多取代1，2-氮杂硼和4，9-BN-的BSRC方法 分别从容易获得的环丙基酮和氮丙基吡啶(AZP)中提取喹啉类化合物。 具体来说，我们将进行反应发现、方法优化、范围探索和 机理研究。预计拟议的研究将提供一种新的方法来简化 1，2-氮杂硼类化合物的合成，从而加速了新型化合物的制备 药物类似物，拓展药物发现的化学空间。

Abstract: As an emerging class of bioisosteres of aromatic compounds, 1,2-azaborines have received increasing attention in drug discovery. However, the current synthesis of 1,2- azaborines encounters substantial difficulties, including how to access poly-substituted 1,2- azaborines and BN-heteroarenes, how to avoid using expensive catalysts and handling sensitive intermediates, how to increase modularity and scalability, etc. Here, we propose to develop a boron-mediated strain-release reductive cyclization (BSRC) strategy to address these accessibility and practicality challenges. Our objective, in the proposed funding period, is to establish the BSRC method for preparing multi-substituted 1,2-azaborines and 4,9-BN- quinolines from readily available cyclopropyl ketones and aziridyl pyridines (AZPs), respectively. Specifically, we will conduct the reaction discovery, method optimization, scope exploration, and mechanism studies. The proposed research is expected to offer a new approach for streamlined synthesis of 1,2-azaborines, which, in turn, should accelerate preparation of novel pharmaceutical analogues and expand the chemical space for drug discovery.