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

摘要: 1,2-氮杂硼烷作为一类新兴的芳香族化合物生物电子等排体，在生物电子等排体中的应用 在药物发现中受到越来越多的关注。然而，目前1,2-的合成 氮硼烷遇到了很大的困难，包括如何获得多取代的1,2- 氮杂硼烷和氮化硼杂芳烃，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 开发硼介导的应变释放还原环化（BSRC）策略来解决这些问题 可访问性和实用性挑战。我们的目标是在拟议的资助期内 建立了制备多取代1,2-氮杂硼烷和4,9-BN-的BSRC方法 分别从容易获得的环丙基酮和氮丙啶基吡啶（AZP）中制备喹啉。 具体来说，我们将进行反应发现、方法优化、范围探索和 机制研究。拟议的研究预计将为简化流程提供新方法 1,2-氮杂硼烷的合成，这反过来又会加速新型药物的制备 药物类似物并扩大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.