A synthesis of γ-trifluoromethyl α,β-unsaturated γ-butyrolactones using CF3SiMe3 as a trifluoromethylating agent

Abstract

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.

Trifluoromethyltrimethylsilane: Nucleophilic Trifluoromethylation and Beyond

“…Pohmakotr and co-workers showed that the corresponding TFMKs could be involved in the TBAT-catalyzed (10 mol %, TBAT: tetrabutylammonium triphenyldifluorosilicate) nucleophilic trifluoromethylation of 1 to phthalic anhydride or succinic anhydride followed by treatment of the adducts with Grignard reagents. , Catalyzed by TBAT, trifluoromethylation of the masked maleic anhydride (cyclopentadiene-maleic anhydride adduct) with 1 followed by quenching with water affords the desired adduct in high diastereoselectivity and yield by attacking of 1 from the less hindered convex side of the substrate (eq 1). Whereas, a complex mixture was produced from the reaction of maleic anhydride with 1 under similar reaction conditions even under low temperature (eq 2). …”

“… Whereas, a complex mixture was produced from the reaction of maleic anhydride with 1 under similar reaction conditions even under low temperature (eq 2). …”

“…111,112 Catalyzed by TBAT, trifluoromethylation of the masked maleic anhydride (cyclopentadiene-maleic anhydride adduct) with 1 followed by quenching with water affords the desired adduct in high diastereoselectivity and yield by attacking of 1 from the less hindered convex side of the substrate (eq 1). 113 Whereas, a complex mixture was produced from the reaction of maleic anhydride with 1 under similar reaction conditions even under low temperature (eq 2). 113 Recently, a research for the addition reaction of 1 to phthalic anhydrides showed that CuI is a good catalyst (CuI: 10 mol %; 1,10-phenanthroline (Phen): 10 mol %; KF: 2 equiv, giving 3hydroxy-3-(trifluoromethyl)isobenzofuran-1(3H)-one in 85% isolated yield) 114 comparied with TBAF (no reaction was observed).…”

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

“…α,α‐Difluoro‐α‐phenylsulfanyl‐α‐trimethylsilylmethane (PhSCF 2 SiMe 3 , 1 ), first introduced by Prakash and co‐workers, has received popularity as a useful difluoromethyl4 and gem ‐difluoromethylene5 building block. Recently, we reported the efficient fluoride‐catalyzed nucleophilic addition of CF 3 SiMe 3 and PhSCF 2 SiMe 3 ( 1 ) to simple anhydrides4f,6 and a masked maleic anhydride 5j,7. After synthetic manipulation of the respective adducts, the corresponding γ‐trifluoromethyl γ‐butyrolactones,6 γ‐trifluoromethyl α,β‐unsaturated γ‐butyrolactones,7 and gem ‐difluoromethylenated polycyclic cage lactones5j were obtained.…”

“…Recently, we reported the efficient fluoride‐catalyzed nucleophilic addition of CF 3 SiMe 3 and PhSCF 2 SiMe 3 ( 1 ) to simple anhydrides4f,6 and a masked maleic anhydride 5j,7. After synthetic manipulation of the respective adducts, the corresponding γ‐trifluoromethyl γ‐butyrolactones,6 γ‐trifluoromethyl α,β‐unsaturated γ‐butyrolactones,7 and gem ‐difluoromethylenated polycyclic cage lactones5j were obtained. In connection of our work on developing general methodologies for the preparation of difluoromethyl‐containing compounds employing 1 as a difluoromethylating agent, we report herein a synthetic route to γ‐difluoromethyl α,β‐unsaturated γ‐butyrolactones 6 .…”