Synthesis of gem‐Difluorocyclopropa(e)nes and O‐, S‐, N‐, and P‐Difluoromethylated Compounds with TMSCF₂Br

Abstract

Two-in-one: Me3 SiCF2 Br is an efficient difluorocarbene source and is compatible with both neutral and aqueous basic conditions. Bromide-ion-initiated [2+1] cycloaddition with alkenes/alkynes and hydroxide ion promoted α-addition with (thio)phenols, (thio)alcohols, sulfinates, heterocyclic amines, and H-phosphine oxides give the corresponding gem-difluorinated compounds with broad functional-group tolerance.

Direct S-difluoromethylation of thiols using the Ruppert–Prakash reagent

“…Others and us have been exploring its direct use and reactivity as a difluoromethylene transfer reagent as we can reduce the cost and efforts associated with additional synthetic steps (Scheme 1) [16]. [17 ], TMSCF 2 Br [18] and TMSCF 2 H [10] have been utilized for the Sdifluoromethylation of thiols, TMSCF 3 has never been directly employed until now. Scheme 1.…”

The Generation of Difluoroketenimine and Its Application in the Synthesis of α,α‐Difluoro‐β‐amino Amides

“…Theprogress of the reaction was monitored by 19 FNMR. Theprogress of the reaction was monitored by 19 FNMR.…”

“…[b] The yields before work-up with acid were determined by 19 FNMR with PhCF 3 as the internals tandard. The yield of the work-up step is quantitative.…”

“…According to our hypothesis,s hown in Scheme 1c,d ifluoroketenimine is first generated, followed by [2+ +2] cycloaddition to give fourmembered ring intermediate.T op rove the existence of difluoroketenimine,amixture of 2a, 3,a nd 30 %T BABw as heated at 60 8 8Ca nd the reaction was monitored by 19 FNMR using trifluorotoluene as the internal standard. According to our hypothesis,s hown in Scheme 1c,d ifluoroketenimine is first generated, followed by [2+ +2] cycloaddition to give fourmembered ring intermediate.T op rove the existence of difluoroketenimine,amixture of 2a, 3,a nd 30 %T BABw as heated at 60 8 8Ca nd the reaction was monitored by 19 FNMR using trifluorotoluene as the internal standard.…”

“…Theg eneration of difluorocarbene via a-elimination of 3 has been previously documented. During the process some signals were observed between À100 and À130 ppm in 19 FNMR spectrum. After 3min, as inglet of À145.7 ppm appeared, which could be assigned to the signal of difluoroketenimine 8 (Scheme 4a).…”