Difluorocarbene enables to access 2-fluoroindoles from ortho-vinylanilines

• DOI: 10.1038/s41467-021-25313-z
• Publication Date: 2021-08-17T10:05:02Z
• Authors: Jianke Su; Xinyuan Hu; Hua Huang; Yu Guo; Qiuling Song
• Keywords: Difluorocarbene; Triple bond; Bond cleavage; Fluorine; Chemoselectivity

2-Fluoroindoles as an important structural scaffold are widely existing in many bioactive or therapeutic agents. Despite their potential usefulness, efficient constructions of 2-fluoroindole derivatives very sparce. The development straightforward synthetic approaches to access 2-fluoroindoles is highly desirable for studying fundamental properties and applications. Herein, we report general strategy the construction which a wide variety were accessed with high efficiency chemoselectivity. Instead starting from indole skeletons, our constructs scaffolds alongside incorporation fluorine atom on C2 position formal [4+1] cyclization readily accessible ortho-vinylanilines difluorocarbene. In protocol, commercially halodifluoroalkylative reagents provide one carbon by cleaving C-N tertiary bond forming C-C double ortho-vinylanilines. Downstream transformations lead various valuable molecules demonstrated significant advantages over previous reports. And mechanistic studies suggest that reaction undergoes cascade difluorocarbene-trapping intramolecular Michael addition followed Csp3-F cleavage.