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

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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.