The synthesis of gem-difluoromethylenated polycyclic cage compounds, utilizing PhSCF2SiMe3 as a gem-difluoromethylene building block, is described. The fluoride-catalyzed nucleophilic addition of PhSCF2SiMe3 to both maleic anhydride-cyclopentadiene and maleic anhydride-cyclohexadiene adducts was accomplished with high stereoselectivity to provide the corresponding adducts that were treated with Grignard reagents, followed by acid-catalyzed lactonization to afford the corresponding γ-butyrolactones, each as a single isomer. These γ-butyrolactones underwent intramolecular radical cyclization to give the corresponding tetracyclic cage γ-butyrolactones, which were employed as precursors for the synthesis of gem-difluoromethylenated tetracyclic cage lactols or tetracyclic cage furans, upon treatment with Grignard reagents.

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A general synthesis of γ-trifluoromethyl α,β-unsaturated γ-butyrolactones is described. The fluoride-catalyzed nucleophilic addition of a trifluoromethyl (CF3) group generated from (trifluoromethyl)trimethylsilane (CF3SiMe3, Ruppert-Prakash reagent) to a masked maleic anhydride 1 (cyclopentadiene-maleic anhydride adduct) provides the corresponding adducts 2 with high stereoselectivity. The γ-trifluoromethyl α,β-unsaturated γ-butyrolactones 4 were obtained after treatment of the adducts 2 with Grignard reagents, followed by flash-vacuum pyrolysis.

A general synthetic strategy to cis-fused bicyclic γ-butyrolactones via the retro-Diels-Alder reaction/intramolecular conjugate ene cascade (RDA/ICE) reaction under the flash-vacuum pyrolysis of maleic anhydride adducts is developed. The reaction gave high yields of products with high stereoselectivity. The existence of the difluoromethyl or trifluoromethyl group at the γ-position of the in situ-generated homoalkenyl- or homoalkynyl-α,β-unsaturated γ-butyrolactones was found to accelerate the rate of the intramolecular conjugate ene reaction leading to γ-difluoromethylated and γ-trifluoromethylated cis-fused bicyclic γ-butyrolactones.

The synthesis of γ‐difluoromethyl α,β‐unsaturated γ‐butyrolactones using PhSCF2SiMe3 (1) as a difluoromethylating agent is described. The method involves the fluoride‐catalyzed nucleophilic addition of 1 to a masked maleic anhydride 2 (cyclopentadiene–maleic anhydride adduct) to give key adduct 3. This adduct can be converted into γ‐difluoromethyl α,β‐unsaturated γ‐butyrolactones 6 through reductive cleavage of the phenylsulfanyl group, stereoselecive nucleophilic addition reaction with Grignard reagents, followed by flash‐vacuum pyrolysis.