Robin D. Wilkes

New fluorine-containing building blocks from trifluoroethanol. 1

Abstract A new fluorine containing acyl anion equivalent 1,1-difluoro-2-lithio-2-[(N,N-diethylcarbamato)-ethene 9 has been prepared and trapped with a number of electrophiles in good yields. Transacylation of the first formed lithium alkoxides releases a difluoroenolate, affording difluoromethylketones upon work-up.

A RAPID AND CONVENIENT APPROACH TO FUNCTIONALLY DIVERSE MONOFLUORINATED VINYLIC COMPOUNDS

Abstract Monofluorinated allylic ether 3, synthesised in 4 steps from trifluoroethanol, underwent metallation at the CF vinylic position upon treatment with strong base. Monofluoro vinyllithium 4 was trapped efficiently with a variety of electrophiles, including Group (IV) halides, methyl iodide and benzaldehyde. Attempts to couple monofluoro vinyl stannane 5d with aryl iodides and triflates under palladium catalysis proved only moderately successful. Conversion of 4 to the monofluoro vinylzinc reagent allowed access to monofluoro vinyl iodide 5e, which was successfully coupled with a range of terminal alkynes.

[3,3]-Sigmatropic Rearrangement Routes to β-Fluoro- and β,β-Difluoro-carbonyl Derivatives.

Abstract Difluoroallylic alcohols prepared in two steps from trifluoroethanol underwent a range of Claisen and related [3,3]-rearrangements in moderate to good yield. In one case, the rearrangement product underwent rapid dehydrofluorination to afford an interesting fluorodienal Monofluoroallylic alcohols rearranged more slowly but resisted dehydrofluorination.

Facile [2,3]-rearrangements of difluoroallylic alcohols with CP and CS bond formation

Abstract Primary, secondary and tertiary difluoroallylic alcohols underwent facile [2,3]-rearrangement upon treatment with phenylsulfenyl chloride or chlorodiphenylphosphine, to the corresponding sulfoxides and phosphine oxides. In the primary cases, the rearrangement was considerably slower, while in the tertiary cases, S N 2′ chlorination reactions competed to a significant extent. Heating the sulfoxide products with triethyl phosphite failed to induce conversion back to the allylic alcohols, consistent with the strong preference of the CF 2 centre for the sp 3 hybridisation state.

Functionally diverse monofluorinated vinylic compounds from trifluoroethanol

Abstract Monofluorinated allylic ether 4 was synthesised in 4 steps from trifluoroethanol. Formation of the monofluoro vinyllithium 5 which was stable at up to −50 °C, and subsequent reaction with a wide range of electrophiles gave access to a series of highly functionalised monofluorinated allylic ethers. Effective electrophiles included Group (IV) halides, methyl iodide and benzaldehyde, whilst aliphatic aldehydes proved to be less efficient electrophiles. Use of a monofluoro vinylzinc reagent, prepared by transmetallation of 5 , allowed efficient access to the monofluorovinyl iodide 6e .

Facile syntheses of gem-difluoroalkenes from chlorodifluoromethylketones

Chlorodifluoromethyl ketones reacted with diazomethane to afford epoxides in high yield; upon treatment with butyllithium, the epoxides underwent efficient ring opening to afford 3,3-difluoro-2-alkyl-alken-1-ols, suitable substrates for sigmatropic rearrangement leading to compounds containing a CF2 group in mid-chain.