Highly stereoselective synthesis of monofluoroalkenes from alpha-fluorosulfoximines and nitrones.

between the charge distribution of the amide bond and the fluoroalkene moiety, as well as their dipole moments. Therefore, a monofluoroalkene moiety can be used as a peptidomimetic unit in the design of protease inhibitors; this type of rigid isostere of the peptidic bond can facilitate the cis/ trans conformational control of the replaced peptidic fragment. Numerous synthetic endeavors have been undertaken towards the efficient preparation of monofluoroalkenes; among them, many routes focus on the elimination reactions of vicinal halofluorides, fluorohydrins, fluorosulfoxides and fluorocarboxylates, or the addition–elimination processes from gem-difluoroalkenes. One-step approaches, such as the Horner–Wadsworth–Emmons reaction, Peterson olefination, and Julia–Kocienski olefination, have also been used to synthesize monofluoroalkenes; however, controlling the Z/E-stereoselectivity of monofluoroalkene products in these one-step reactions still remains a challenging task. Herein, we report a highly efficient stereoselective synthesis of (Z)-monofluoroalkenes from an unprecedented reaction between a-fluorosulfoximines and nitrones. Sulfoximines have been widely used in organic synthesis, but fluorinated sulfoximines still remain a relatively poorly studied class of compounds. Previously, Finch and coworkers reported that monofluorinated sulfoximines could react with carbonyl compounds to yield hydroxy adducts, which can be converted into fluoroalkenes (albeit with poor Z/E-selectivity) by reduction with aluminum amalgam. Shibata and co-workers reported a trifluoromethylated sulfoximine derivative as an electrophilic trifluoromethylation reagent. Recently, we reported the use of N-tolyl-Sdifluoromethyl-S-phenylsulfoximine as a novel difluoromethylation reagent for transferring the CF2H group to sulfur, nitrogen, and carbon nucleophiles. Furthermore, although nitrones have been extensively used in organic synthesis, reports on their use as reaction partners in olefination reactions are rare. Indeed, to the best of our knowledge, the olefination reaction between a sulfoximine and a nitrone has not been previously reported. Our investigation began with the preparation of a-fluoroN-tolyl-S-phenylsulfoximines 4a–4e by electrophilic fluorination of non-fluorinated sulfoximines 3a–3e with the Nfluorodibenzenesulfonimide (NFSI) reagent (Scheme 1).