3,3-Difluoroallyl ammonium salts: highly versatile, stable and selective gem-difluoroallylation reagents

• Published in: Nature communications Vol. 12; no. 1; pp. 3257 - 9
• Main Authors: Ye, Fei, Ge, Yao, Spannenberg, Anke, Neumann, Helfried, Xu, Li-Wen, Beller, Matthias
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 31.05.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 639/638/403/933; 639/638/77/888; Agrochemicals; Ammonium; Ammonium salts; Bioactive compounds; Catalysts; Chemical synthesis; Fluorination; Fluorine; Humanities and Social Sciences; multidisciplinary; Nucleophiles; Organic chemistry; Pharmaceuticals; Reagents; Regioselectivity; Salts; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-23504-2

The selective synthesis of fluorinated organic molecules continues to be of major importance for the development of bioactive compounds (agrochemicals and pharmaceuticals) as well as unique materials. Among the established synthetic toolbox for incorporation of fluorine-containing units, efficient and general reagents for introducing -CF 2 - groups have been largely neglected. Here, we present the synthesis of 3,3-difluoropropen-1-yl ammonium salts (DFPAs) as stable, and scalable gem -difluoromethylation reagents, which allow for the direct reaction with a wide range of fascinating nucleophiles. DFPAs smoothly react with N -, O -, S -, Se -, and C -nucleophiles under mild conditions without necessity of metal catalysts with exclusive regioselectivity. In this way, the presented reagents also permit the straightforward preparation of many analogues of existing pharmaceuticals. Synthesis of fluorinated organic molecules is of high interest for agrochemistry and pharmaceutics, but efficient and general reagents for introducing -CF 2 - groups are lacking. Here, the authors report the synthesis of 3,3-difluoropropen-1-yl ammonium salts as stable and scalable gem -difluoromethylation reagents, which react with a range of nucleophiles under mild conditions and high regioselectivity.