Synthesis of monofluorinated C4-building blocks based on methallyl chloride

Article abstract of DOI:10.1016/0022-1139(95)03290-T

Halofluorination of methallyl chloride using N-halosuccinimides in combination with triethylamine trishydrofluoride (Et3N*3HF) gave in each case more than 98percent of the Markovnikov products and < 2percent of the regioisomers in good yield.The formal addition of methanesulfenyl fluoride with the combination of dimethyl(methylthio)sulfonium fluoroborate (DMTSF) and Et3N*3HF gave a 94:6 mixture of both regioisomers.Only small phenylsulfenyl fluorination of methallyl chloride has been observed when treated with N-phenylthiophthalimide (NPTP) and Olah's reagent.With benzenesulfenyl chloride, 1,3-dichloro-2-methyl-2-(phenylthio)propane is formed which on treatment with Olah's reagent at 0 deg C or with Et3N*3HF at 60 deg C rearranges to 1,2-dichloro-2-methyl-3-(phenylthio)propane.Treatment of 1,3-dichloro-2-methyl-2-(phenylthio)propane with silver fluoride in methylene chloride at -30 deg C gave 1-chloro-2-fluoro-2-methyl-3-(phenylthio)propane which was also obtained by reaction of 1-bromo-3-chloro-2-fluoro-2-methylpropane with thiophenolate.Chlorofluorination of methallylphenylthio ether using NCS/Et3N*3HF failed, while corresponding reactions with NBS or NIS and Et3N*3HF gave mainly the bromo- or iodo-fluorides with Markovnikov orientation in 61percent or 35percent yields.Related halofluorinations of methallylphenyl ether gave the halofluorides in good yield.All attempts to obtain chromanes or thiochromanes bearing a 3-fluorine substituent by cyclization of these halofluorinated ethers or thio ethers failed using different Lewis acids.However, the benzyl protected o-allylphenol which was bromofluorinated with NBS/Et3N*3HF in good yield gave on catalytic hydrogenation over Pd/C the 3-fluoro-2H-chromane in nearly quantitative yield. - Keywords: Electrophilic addition; Halofluorination; Sulfenylfluorination; N-Halosuccinimides; Dimethyl(methylthio)sulfonium tetrafluoroborate; Triethylamine trishydrofluoride