Formal [3+3] cyclocondensations of 1,3-bis(silyloxy)-1,3-butadienes with 1-chloro-1,1-difluoro-4,4-dimethoxybut-3-en-2-one and 1,1-difluoro-4,4-dimethoxybut-3-en-2-one. Regioselective synthesis of fluorinated salicylates and pyran-4-ones

The TiCl4-mediated [3+3] cyclocondensation of 1,3-bis(silyloxy)-1,3-butadienes with 1-chloro-1,1-difluoro-4,4-dimethoxybut-3-en-2-one or 1,1-difluoro-4,4-dimethoxybut-3-en-2-one afforded CF2Cl- and CF2H-substituted salicylates, respectively. The Me3SiOTf-mediated [3+3] cyclocondensation of the same building blocks provided CF2Cl- and CF2H-substituted pyran-4-ones and CF2Cl-substituted cyclohexenones. The formation of CF2H-substituted cyclohexenones was not observed. Besides the type of Lewis acid, the product distribution is also influenced by the substitution pattern of the 1,3-bis(silyloxy)-1,3-butadiene: The Me3SiOTf mediated cyclization of C4-unsubstituted dienes resulted in the formation of CF2Cl-substituted pyran-4-ones, while the cyclization of C4-substituted dienes afforded CF2Cl-substituted cyclohexenones. The TiCl4-mediated cyclization of C4-substituted dienes with 1,1-difluoro-4,4-dimethoxybut-3-en-2-one failed. Therefore, 3-substituted CF2H-salicylates were prepared by transformation of the respective CF2Cl-salicylates with tributyltin hydride.

6-Chlorodifluoromethylsalicylates and -pyran-4-ones are prepared by regioselective [3+3] cyclizations of 1,3-bis(silyloxy)-1,3-butadienes with CF2Cl-substituted 3-alkyloxy-2-en-1-ones. The regioselectivity is controlled by the choice of Lewis acid employed.Figure optionsDownload as PowerPoint slideHighlights
► The first formal [3+3] cyclizations of 1,3-bis(silyloxy)-1,3-butadienes with CF2Cl-substituted enones are reported.
► The first 6-chlorodifluoromethylsalicylates and pyranones are prepared.
► The reactions proceed with excellent regioselectivity.
► The regioselectivity can be controlled by the choice of Lewis acid.