Synthesis of γ‐Difluoromethyl α,β‐Unsaturated γ‐Butyrolactones Using PhSCF₂SiMe₃ as a Difluoromethylating Agent

Abstract

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.

Stereoselective Synthesis of gem‐Difluoromethylenated Linear Azatriquinanes

“…In particular, the presence of a gem ‐difluoromethylene (‐CF 2 ‐) moiety in organic molecules has been evidenced to enhance the biological activities of the parent organic compounds . Our research group recently reported the synthesis of gem ‐difluoromethylenated polycyclic cage compounds, dihydroxypyrrolizidines, indolizidines, γ‐butyrolactams, and α,β‐unsaturated γ‐butyrolactones by employing PhSCF 2 SiMe 3 ( 1 ) as the gem ‐difluoromethylene building block. On the basis of our previous report on the asymmetric synthesis of gem ‐difluoromethylenated linear triquinanes, herein we report the stereoselective synthesis of gem ‐difluoromethylenated linear azatriquinanes employing compound 1 as a difluoromethylene motif.…”