Bifluoride Ion Mediated SuFEx Trifluoromethylation of Sulfonyl Fluorides and Iminosulfur Oxydifluorides

Abstract

SuFEx is an ew-generation clickc hemistry transformation that exploits the unique properties of SÀFbonds and their ability to undergo near-perfect reactions with nucleophiles.W ereport 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,r espectively.T he new process involves rapid SÀFe xchange with trifluoromethyltrimethylsilane (TMSCF 3 )u pon activation by potassium bifluoride in anhydrous DMSO.T he reaction tolerates aw ide selection of substrates and proceeds under mild conditions without need for chromatographic purification. At entative mechanism is proposed involving nucleophilic displacement of S À Fb yt he trifluoromethyl anion via af ive-coordinate intermediate.T he utility of late-stage SuFEx trifluoromethylation is demonstrated through the synthesis and selective anticancer properties of abis(trifluoromethyl)sulfur oxyimine.

Fluorosulfonylferrocene, (Trifluoromethylsulfonyl)ferrocene and New Ferrocenyl Sulfonates: Directed ortho Lithiation and New Anionic Thia‐Fries Rearrangements at Ferrocene

“…TASF = tris (dimethylamino)sulfonium difluorotrimethylsilicate. corresponds to [M + 23 Na] + for cyclodimer 32 b, which cannot easily be distinguished from 32 a by standard NMR measurements. In both cases, the presence of tetrahydrofuranyl substituents can be explained by a lithiation at C2 of a THF molecule followed by reaction with 25 forming (ferrocenyl)(2tetrahydrofuranyl)sulfone (32 a).…”

“…[18] Following this, ferrocenyl acetate ( 16) was treated with potassium hydroxide in water followed by acid hydrolysis. Without isolation, the intermediate ferrocenol (23) was treated with sulfuryl fluoride in the presence of triethylamine affording ferrocenyl fluorosulfonate (8) in 74 % yield. The desired anionic thia-Fries rearrangement was finally realized by treatment of 8 with lithium diisopropylamide at À 78 °C for 40 min followed by warming to 0 °C over 30 min and hydrolytic workup giving 2-(fluorosulfonyl)ferrocenol (rac-24), which was isolated as an oxygen sensitive compound not undergoing hydrolysis, in 91 % yield (Scheme 5).…”

“…An approach to prepare 6 by treatment of sulfonyl chloride 25 with copper(I) iodide and sodium trifluoroacetate in DMF failed, [22] and another attempt making use of the SuFEx protocol by Moses et al treating sulfonyl fluoride 7 with KHF 2 and (trifluoromethyl)trimethylsilane (Ruppert's reagent) was also unsuccessful. [23] Finally, 6 was obtained in moderate yield of 46 % following a route of Yagupolski et al [24] by treatment of sulfonyl fluoride 7 with (trifluoromethyl)trimethylsilane in the presence of a catalytic amount (10 mol %) of tris (dimethylamino)sulfonium difluorotrimethylsilicate (TASF) (Scheme 7).…”

“…After analysis of the NMR and IR spectra of the side product, constitution 32 a was considered. The ESI mass spectrum shows a peak at m/z = 344 corresponding to [M + 23 Na] + for compound 32 a. However, there is also a signal at m/z = 663, which Scheme 6.…”

Linkage Chemistry of S(VI) Fluorides

“…However, the high‐hydrophilic character of TBAF enables excess TMSCF 3 to be required. Difluoride anion as a superb catalyst has successfully been applied in the O ‐SuFEx polymerization, [11b,c] and accordingly, Moses and coworkers leveraged the catalyst to develop a CF 3 ‐SuFEx strategy of sulfonyl fluorides and iminosulfur oxydifluorides in 2019 (Scheme 15a) [52] . A possible catalytic cycle is presented as a representative mechanism (Scheme 15b), where the trifluoromethylation of sulfur(VI) fluorides proceeds via a five‐coordinate intermediate Int‐30 .…”