Trifluoromethyl Rhodium‐Carbynoid in [2+1+2] Cycloadditions

作者：Wenwen Zhao, Meng‐Yang Tian, Yilin Zhou, Lujie Liu, Shao‐Fang Tian, Chun‐Yang He, Xing‐Zhi Yang, Yong‐Zheng Chen, Wen‐Yong Han · 发表于：Angewandte Chemie · 年份：2024 · DOI：10.1002/ange.202318887 · 被引用次数：3 · 研究领域：Fluorine in Organic Chemistry、Organometallic Complex Synthesis and Catalysis、Cyclopropane Reaction Mechanisms

Abstract Trifluoromethyl cationic carbyne (CF 3 C + :) possessing dual carbene‐carbocation behavior emulated as trifluoromethyl metal‐carbynoid (CF 3 C + =M) has not been explored yet, and its reaction characteristics are unknown. Herein, a novel α‐diazotrifluoroethyl sulfonium salt was prepared and used in Rh‐catalyzed three‐component [2+1+2] cycloadditions for the first time with commercially available N ‐fused heteroarenes and nitriles, yielding a series of imidazo[1,5‐ a ] N ‐heterocycles that are of interest in medicinal chemistry, in which the insertion of trifluoromethyl Rh‐carbynoid (CF 3 C + =Rh) into C=N bonds of N ‐fused heteroarenes was involved. This strategy demonstrates synthetic applications in late‐stage modification of pharmaceuticals, construction of CD 3 ‐containing N ‐heterocycles, gram‐scale experiments, and synthesis of phosphodiesterase 10A inhibitor analog. These highly valuable and modifiable imidazo[1,5‐ a ] N ‐heterocycles exhibit good antitumor activity in vitro, thus demonstrating their potential applications in medicinal chemistry.