Nie Zhiwen, Wu Keqin, Zhan Xiaohang, Yang Weiran, Lian Zhong, Lin Shaoquan, Wang Shou-Guo, Yin Qin
Shenzhen University of Advanced Technology, Shenzhen, 518055, P. R. China.
Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, P. R. China.
Nat Commun. 2024 Oct 1;15(1):8510. doi: 10.1038/s41467-024-52392-5.
We disclose herein an unprecedented Pd-catalyzed difluorocarbene transfer reaction, which assembles a series of structurally interesting chiral spiro ketones with generally over 90% ee. Commercially available BrCFCOK serves as the difluorocarbene precursor, which is harnessed as a user-friendly and safe carbonyl source in this transformation. Preliminary mechanistic studies exclude the formation of free CO in the reaction process, and importantly, we also find that BrCFCOK outcompete gaseous CO and several common CO surrogates in this asymmetric process. The reaction mechanism, including the in-situ progressive release of the difluorocarbene, the rapid migratory insertion of ArPd(II) = CF species, and subsequent defluorination hydrolysis by water to introduce the carbonyl group, accounts for the overall high efficiency and uniqueness. This work clearly showcases the advantage and potential of the difluorocarbene in synthesis and supplies a mechanistically distinct route for asymmetric carbonylative cyclization reactions.
我们在此披露一种前所未有的钯催化二氟卡宾转移反应，该反应可组装一系列结构有趣的手性螺环酮，其对映体过量（ee）通常超过90%。市售的BrCF₂COK用作二氟卡宾前体，在该转化过程中作为一种使用方便且安全的羰基源。初步机理研究排除了反应过程中游离CO的形成，重要的是，我们还发现BrCF₂COK在该不对称过程中比气态CO和几种常见的CO替代物更具优势。反应机理，包括二氟卡宾的原位逐步释放、ArPd(II)=CF物种的快速迁移插入以及随后水的脱氟水解以引入羰基，解释了整体的高效率和独特性。这项工作清楚地展示了二氟卡宾在合成中的优势和潜力，并为不对称羰基化环化反应提供了一种机理独特的途径。
