Organocatalytic, difluorocarbene-based S-difluoromethylation of thiocarbonyl compounds

•Upon treatment with TFDA and proton sponge, thioamides and thiocarbamates undergo S-selective difluoromethylation.•S-Difluoromethyl thioimidates and thioiminocarbonates were obtained in good yields.•The key for S-difluoromethylation is the organocatalytic generation of difluorocarbene (:CF2) under mild conditions.•This is an efficient approach to pharmaceuticals and agrochemicals bearing a difluoromethylsulfanyl group.

Upon treatment with trimethylsilyl 2,2-difluoro-2-fluorosulfonylacetate (TFDA) and a catalytic amount of N,N,N′,N′-tetramethyl-1,8-diaminonaphthalene, secondary thioamides and thiocarbamates undergo selective difluoromethylation on the sulfur atom to give S-difluoromethyl thioimidates and thioiminocarbonates in good yields, respectively. This is the first report on the synthesis of acyclic difluoromethyl thioimidates and thioiminocarbonates. The key for S-difluoromethylation is the organocatalytic generation of difluorocarbene (:CF2) under mild conditions, which prevents decomposition of the substrates. This process provides an efficient approach to pharmaceuticals and agrochemicals bearing a difluoromethylsulfanyl group, starting from widely available thiocarbonyl compounds.

Graphical abstractUpon treatment with trimethylsilyl 2,2-difluoro-2-fluorosulfonylacetate (TFDA) and a catalytic amount of N,N,N′,N′-tetramethyl-1,8-diaminonaphthalene, secondary thioamides and thiocarbamates undergo selective difluoromethylation on the sulfur atom to give S-difluoromethyl thioimidates and thioiminocarbonates in good yields, respectively. The key for S-difluoromethylation is the organocatalytic generation of difluorocarbene (:CF2) under mild conditions. This process provides an efficient approach to pharmaceuticals and agrochemicals bearing a difluoromethylsulfanyl group, starting from widely available thiocarbonyl compounds.Figure optionsDownload full-size imageDownload as PowerPoint slide