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

• Published in: Journal of fluorine chemistry Vol. 139; pp. 28 - 45
• Main Authors: Reimann, Sebastian, Bunescu, Alina, Litschko, Robert, Erfle, Silke, Domke, Lutz, Bendrath, Franziska, Abilov, Zharylkasyn A., Spannenberg, Anke, Villinger, Alexander, Langer, Peter
• Format: Journal Article
• Language: English
• Published: LAUSANNE Elsevier B.V 01.07.2012; Elsevier
• Subjects: Chemistry; Chemistry, Inorganic & Nuclear; Chemistry, Organic; Cyclizations; Dienes; Fluorine; Formations; Hydrides; Lewis acid; Lewis acids; Organofluorine compounds; Physical Sciences; Regioselectivity; Salicylates; Science & Technology; Silyl enol ethers; Synthesis (chemistry); Transformations; Silyl enol ethers; Lewis acids; Organofluorine compounds; Cyclizations; Regioselectivity; LEWIS-ACID; EFFICIENT SYNTHESIS; SILYL ETHERS; DUAL-ACTION CEPHALOSPORINS; BENZYLIC FLUORIDES; COUPLING REACTIONS; INHIBITORS; 1,3-BIS-SILYL ENOL ETHERS; IONIC LIQUIDS; METAL-FREE
• ISSN: 0022-1139; 1873-3328
• DOI: 10.1016/j.jfluchem.2012.03.019

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. [Display omitted] ► 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. 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.