Nucleophilic trifluoromethylation of anhydrides employing (trifluoromethyl)trimethylsilane: Synthesis of γ-trifluoromethylated γ-butyrolactones

Nucleophilic non-metal assisted trifluoromethylation and perfluoroalkylation reactions of organic substrates

“…The authors postulate a plausible mechanism for the trifluoromethylation reaction of aldehydes and ketones with reagent 7 such as that depicted in Scheme 15. A c c e p t e d M a n u s c r i p t 19 Scheme 15. Plausible mechanism for the trifluoromethylation of aldehydes with diethyl trifluoromethylphosphonate in the presence of potassium phenolate.…”

“…TBAT = tetrabutyl ammonium triphenyldifluorosilicate. p-TsOH : ptoluensulfonic acid.This constitutes a fluoride ion-catalyzed nucleophilic addition of Me 3 SiCF 3 to anhydrides which provides γ-hydroxy-γ-trifluoromethyl-γ-butyrolactones that can be transformed to γ-trifluoromethylated-γ-butyrolactones upon treatment with Grignard reagents and ulterior lactonization[19].Alkyl perfluorodithioesters and analogues react with various nucleophiles at sulfur of the thiocarbonyl group (thiophilic attack) with subsequent β-elimination of a fluoride [20], according to Scheme 5. Scheme 5.…”

Nucleophilic fluoroalkylation/cyclization route to fluorinated phthalides

“…In 2006, Pedrosa et al reported the nucleophilic trifluoromethylation of protected ortho -phthalaldehyde, followed by deprotection and oxidation to afford 3-(trifluoromethyl)phthalide [ 12 ]. Pohmakotr et al demonstrated the nucleophilic trifluoromethylation of acid anhydrides to produce γ-hydroxy-γ-trifluoromethyl-γ-butyrolactones, which acted as good precursors in the synthesis of γ-trifluoromethyl-γ-butyrolactones with organometallic reagents [ 16 ]. All these protocols involve multiple steps to obtain trifluoromethylphthalides.…”

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 .…”