Synthesis of new fluorinated synthons: (E and Z) ClFCCFI and (E and Z) BrFCCFI

•E and Z-XCFCFI (X = Br, Cl) are stereospecifically prepared in 4 steps.•C6H5I·Cl2 stereospecifically chlorinates 1,2-difluorovinylstannanes.•E or Z HFCCF(SiMe3) can be prepared stereospecifically from F2CCF(SiMe3).

(E)- and (Z)-1,2-difluoro-1-(trimethylsilyl)ethenes are readily prepared from trifluorovinyl(trimethyl)silane. These hydro compounds are readily metalated at low temperatures to give a stable lithium intermediate which can be captured by tri-n-butylstannyl chloride to give (E)- and (Z)-1,2-difluoro-2-trimethylsilyl-1-(tri-n-butylstannyl)ethenes. The stannyl derivatives can be halogenated stereospecifically with iodobenzene dichloride and NBS to provide the (E)- and (Z)-1-halo-1,2-difluoro-2-(trimethylsilyl)ethenes. The vinylsilanes can be readily converted in two steps to the titled synthons, (E)- and (Z)-2-halo-1,2-difluoro-1-iodoethenes by literature procedures. (E)- and (Z)-1,2-difluoro-1-(trimethylsilyl)ethenes boil ∼30 °C apart and are readily separated by fractional distillation.

Graphical abstractTrifluorovinyl(trimethyl)silane can be prepared from the trifluorovinyl zinc reagent in DMF in 74% isolated yield. This silane can be reduced by LAH to give mainly (Z)-1,2-difluoro-1-(trimethylsilyl)ethene which was purified by fractional distillation, bp 69 °C – 87% isolated yield. Subsequent photochemical isomerization of (Z)-1,2-difluoro-1-(trimethylsilyl)ethene at 254 nm, gave 75% of (E)-1,2-difluoro-1-(trimethylsilyl)ethene, bp 97 °C. These E/Z isomers could be metalated with either LiTMP or LDA at low temperature to provide corresponding lithium reagent, which could be captured with tri-n-butylstannyl chloride to give the corresponding stannane reagent. Subsequent reaction of the stannane reagent with benzyltriethylammonium chloride and iodobenzene dichloride in DMF provided the corresponding (E)- or (Z)-1-chloro-1,2-difluoro-2-(trimethylsilyl)ethene. Similar reaction of the E or Z stannane reagent with NBS gave the corresponding (E)- or (Z)-1-bromo-1,2-difluoro-2-(trimethylsilyl)ethene. Subsequent reaction of the 1-halo-1,2-difluoro-2-(trimethylsilyl)ethene with KF and bis(tributyltin) oxide stereospecifically gave 2-halo-1,2-difluoro-1-(tri-n-butylstannyl)ethene, which on subsequent reaction with iodine stereospecifically gave 2-halo-1,2-difluoro-1-iodo-ethene.Figure optionsDownload full-size imageDownload as PowerPoint slide