Bifluoride Ion Mediated SuFEx Trifluoromethylation of Sulfonyl Fluorides and Iminosulfur Oxydifluorides

Angewandte Chemie
Christopher J SmedleyJohn E Moses

Abstract

SuFEx is a new-generation click chemistry transformation that exploits the unique properties of S-F bonds and their ability to undergo near-perfect reactions with nucleophiles. We report here the first SuFEx-based procedure for the efficient synthesis of pharmaceutically important triflones and bis(trifluoromethyl)sulfur oxyimines from sulfonyl fluorides and iminosulfur oxydifluorides, respectively. The new process involves rapid S-F exchange with trifluoromethyltrimethylsilane (TMSCF3 ) upon activation by potassium bifluoride in anhydrous DMSO. The reaction tolerates a wide selection of substrates and proceeds under mild conditions without need for chromatographic purification. A tentative mechanism is proposed involving nucleophilic displacement of S-F by the trifluoromethyl anion via a five-coordinate intermediate. The utility of late-stage SuFEx trifluoromethylation is demonstrated through the synthesis and selective anticancer properties of a bis(trifluoromethyl)sulfur oxyimine.

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Citations

Aug 1, 2019·Chemical Society Reviews·A S BarrowJ E Moses
Sep 6, 2019·Proceedings of the National Academy of Sciences of the United States of America·Qinheng ZhengK Barry Sharpless
May 8, 2020·Chemistry : a European Journal·Sebastian Hasenstab-RiedelJulia Bader
Nov 17, 2020·Angewandte Chemie·Xingliang NieSaihu Liao
May 7, 2021·Chemical Communications : Chem Comm·Yiyuan ZhangHongtao Xu
Aug 26, 2020·Journal of the American Chemical Society·Thomas Q DaviesMichael C Willis
Nov 2, 2019·The Journal of Organic Chemistry·Shuning ZhangGuang Yang
Jun 27, 2020·Organic Letters·Young-Do KwonJoong-Hyun Chun

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