Difluoromethanesulfonyl hypervalent iodonium ylides for electrophilic difluoromethylthiolation reactions under copper catalysis

Abstract

Difluoromethanesulfonyl hypervalent iodonium ylides 2 were developed as electrophilic difluoromethylthiolation reagents for a wide range of nucleophiles. Enamines, indoles, β-keto esters, silyl enol ethers and pyrroles were effectively reacted with 2 affording desired difluoromethylthio (SCF2H)-substituted compounds in good to high yields under copper catalysis. The reaction of allyl alcohols with 2 under the same conditions provided difluoromethylsulfinyl (S(O)CF2H) products in good yields. The difluoromethylthiolation of enamines is particularly effective with wide generality, thus the enamine method was nicely extended to the synthesis of a series of difluoromethythiolated cyclic and acyclic β-keto esters, 1,3-diketones, pyrazole and pyrimidine derivatives by a consecutive, two-step one-pot reaction using 2.

Exploration of new reaction tools for late-stage functionalization of complex chemicals

“…As a key contribution, the Shen group disclosed the first nucleophilic difluoromethylthiolating reagent 43, [(SIPr)Ag(SCF 2 H)] and achieved the direct difluoromethylthioether synthesis by coupling 43 and aryl (pseudo)halides via transition metal catalysis (M = Pd or Cu) (Scheme 28b) [168][169]. Following this pioneering work, several reagents with complementary reactivity 44-47 were described independently by Shen,[170][171][172] Shibata,173 Billard174 and Besset 175 et al Using these reagents under thermal conditions, electron-rich arenes can be difluoromethylthiolated through a Friedel-Craft type reaction. Despite these promising strategies, the preparation of the difluoromethylthioethers still relied on relatively high thermal energy (from 50 to 120 ) or involved precious metal catalysts and stoichiometric additives.…”

Recent Progress on Direct Difluoromethylthiolation and Monofluoromethylthiolation

“…2013 年, Shibata 课题组 [34] 开发出了一种基于高价 碘叶立德类型的亲电三氟甲硫基化试剂, 并在此工作基 础上于 2016 年制得了一类结构新颖且高效的高碘二氟 甲硫基化试剂 [35] . 吲哚和吡咯等)底物发生反应, 收率中等 [35] . 此外, 作者 还进一步拓展了该试剂在手性化合物合成方面的应用.…”

Radical difluoromethylthiolation of aromatics enabled by visible light

“…Shortly after, Shibata et al uncovered a hypervalent difluoromethanesulfonyliodonium ylide reagent 3 , which efficiently difluoromethylthiolated N-heterocycles under copper catalysis. 15 Moreover, the Billard, 16 Besset 17 and Shen 18 groups independently synthesized three electrophilic –SCF 2 FG group transfer reagents (FG = PhSO 2 , PO(OEt) 2 and CO 2 Et respectively), although a separate reductive workup was necessary to give difluoromethylthioethers. Inspired by these elegant examples, other difluoromethylthiolating systems were unveiled.…”