SYNTHESIS OF MONOFLUORINATED C-4-BUILDING BLOCKS BASED ON METHALLYL CHLORIDE

Halofluorination of methallyl chloride using N-halosuccinimides in com bination with triethylamine trishydrofluoride (Et(3)N . 3HF) gave in e ach case more than 98% of the Markovnikov products and <2% of the regi oisomers in good yield. The formal addition of methanesulfenyl fluorid e with the combination of dimethyl(methylthio)sulfonium fluoroborate ( DMTSF) and Et(3)N . 3HF gave a 94:6 mixture of both regioisomers. Only small phenylsulfenyl fluorination of methallyl chloride has been obse rved when treated with N-phenylthiophthalimide (NPTP) and Olah's reage nt. With benzenesulfenyl chloride, 1,3-dichloro-2-methyl-2- (phenylthi o) propane is formed which on treatment with Olah's reagent at 0 degre es C or with Et(3)N . 3HF at 60 degrees C rearranges to 1,2-dichloro-2 -methyl-3-(phenylthio)propane. Treatment of 1,3-dichloro-2-methyl-2-(p henylthio)propane with silver fluoride in methylene chloride at -30 de grees C gave 1-chloro-2-fluoro-2-methyl-3-(phenylthio) propane which w as also obtained by reaction of 1 -bromo-3-chloro-2-fluoro-2-methylpro pane with thiophenolate. Chlorofluorination of methalylphenylthio ethe r using NCS/Et(3)N . 3HF failed, while corresponding reactions with NB S or NIS and Et(3)N . 3HF gave mainly the bromo- or iodo-fluorides wit h Markovnikov orientation in 61% or 35% yields. Related halofluorinati ons of methallylphenyl ether gave the halofluorides in good yield. All attempts to obtain chromanes or thiochromanes bearing a 3-fluorine su bstituent by cyclization of these halofluorinated ethers or thio ether s failed using different Lewis acids. However, the benzyl protected o- allylphenol which was bromofluorinated with NBS/Et(3)N . 3HF in good y ield gave on catalytic hydrogenation over Pd/C the 3-fluoro-2H-chroman e in nearly quantitative yield.