Difluoromethylation and gem-difluorocyclopropenation with difluorocarbene generated by decarboxylation

Abstract

Difluoromethylation of the activated X-H bond (X = N, O and S) and aliphatic thiols, and gem-difluorocyclopropenation of alkynes with difluorocarbene generated in situ from difluoromethylene phosphobetaine (Ph3P(+)CF2CO2(-)) by decarboxylation occurred smoothly without the presence of any base or other additives.

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

“…A common approach to synthesize difluoromethyl thioethers is to use difluorocarbene based reagents such as ClCF 2 CO 2 Na [3], CF 2 HCl [4], CF 3 H [5], BrCF 2 PO(OEt) 2 [6], and ArSONRCF 2 H [7] and Ph 3 P + CF 2 CO 2 - [8]. An electrophilic reagent, ArSONR 2 CF 2 H + , transferring -CF 2 H to nucleophiles has also been used [9].…”

Nucleophilic arylation with tetraarylphosphonium salts

“…Our research interest in the chemistry of organic phosphonium salts 26 27 28 29 prompted us to investigate their application in arylation reactions. Organic phosphonium salts have served as important intermediates in synthetic chemistry 30 31 32 33 34 35 .…”

A General Protocol for C−H Difluoromethylation of Carbon Acids with TMSCF2Br

“…Amide 3 g , which underwent difluoromethylation with TMSCF 2 Br to give 4 g in 72 % yield (Scheme ), was selected as a model substrate. Under the optimized and modified reaction conditions,, difluorocarbene reagents B1 – B6 showed low reactivity towards 3 g , and the desired product 4 g was formed in low yields (0–36 %), with most of 3 g being recovered. These results highlight the unique reactivity and advantage of TMSCF 2 Br as a privileged difluorocarbene precursor.…”