Synthesis of trifluoromethyl-substituted salicylates by cyclocondensation of 1,3-bis(silyloxy)-1,3-butadienes with 4,4-dimethylthio-1,1,1-trifluorobut-3-en-2-one

A formal [3+3] cyclocondensation of 1,3-bis(silyl enol ethers) with the little-known 4,4-dimethylthio-1,1,1-trifluorobut-3-en-2-one was studied. In contrast to 4,4-dimethoxy-1,1,1-trifluorobut-3-en-2-one, this α-oxoketene dithioacetal reacts with 1,3-bis(trimethylsilyloxy)-1,3-butadienes in the presence of TiCl4 to give mainly 6-methylthio-4-(trifluoromethyl)salicylates via 1,2-addition. The scope and limitations of the reaction are discussed.

A formal [3+3] cyclocondensation of 1,3-bis(silyl enol ethers) with the little-known 4,4-dimethylthio-1,1,1-trifluorobut-3-en-2-one was studied. In contrast to 4,4-dimethoxy-1,1,1-trifluorobut-3-en-2-one, this α-oxoketene dithioacetal reacts with 1,3-bis(trimethylsilyloxy)-1,3-butadienes in the presence of TiCl4 to give mainly 6-methylthio-4-(trifluoromethyl)salicylates via 1,2-addition. The scope and limitations of the reaction are discussed.Figure optionsDownload as PowerPoint slideHighlights
► This manuscript deals with the study of two-component reaction of 1,3-bis(silyloxy)-1,3-butadienes with 4,4-dimethylthio-1,1,1-trifluorobut-3-en-2-one, catalyzed by Lewis acids as well as TMS-triflate.
► This formal [3+3]-cyclization depends on structure of bis-silyls and catalyst loaded, delivers set of three deferent products.
► In this communication we have investigated the influence of the catalysts and solvent on the reaction, as a result the scope and limitation were studied.
► Resulting, herewith we have demonstrated the new synthetic strategy towards pharmacologically relevant trifluoromethyl-substituted salicylates bearing additional methyl-mercapto-functionality in the aromatic core.