Key Laboratory of Organosilicon Chemistry and Material Technology of Ministry of Education, and Key Laboratory of Organosilicon Material Technology of Zhejiang Province, Hangzhou Normal University, No. 2318, Yuhangtang Road, Hangzhou, 311121, PR China.
Leibniz-Institute for Catalysis, Albert-Einstein-Str. 29a, Rostock, 18059, Germany.
Nat Commun. 2021 May 31;12(1):3257. 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- 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.
含氟有机分子的选择性合成对于生物活性化合物（农用化学品和药物）以及独特材料的开发仍然至关重要。在引入含氟单元的既定合成工具箱中，用于引入-CF-基团的高效且通用的试剂在很大程度上被忽视了。在这里，我们提出了 3,3-二氟丙烯-1-基铵盐（DFPAs）的合成方法，作为稳定且可规模化的偕二氟甲基化试剂，可与广泛的迷人亲核试剂直接反应。DFPAs 在温和条件下无需金属催化剂即可与 N-、O-、S-、Se-和 C-亲核试剂顺利反应，具有独特的区域选择性。通过这种方式，所提出的试剂还允许直接制备许多现有药物的类似物。
