Syntheses of fluoro compounds by nucleophilic substitution of bromides or methanesulfonates using Et3fi.2HF as the reagent are reported. The formation of undesired elimination side products IS limited. The synthesis of this new fluorinating reagent is also reported. Many methods have been developed for introducing fluorine into an organic compound' and numerous of them consist of reaction of ionic fluoride by nucleophilic substitution. When the nucleophilicity of the fluoride ion is increased, the basicity is also increased and therefore involves the formation of elimination produck "F-" R1R2CH-CHXR3 -m R1R2C=CHR3 t R1R2CH-CHFR3 Recently, Cousseau et of3 have reported that polymer supported dihydrogen trifluoride P+H2F3-(Pfcationic part of a macroreticular basic anion-exchange resin Amberlyst A 26 or Amberlite IRA 900) provided good yields of fluoro substitution without exhibiting any important basic characrer.4 We describe here a new fluorinating reagent, Et3N.2HF (prepared in situ from Et3N.3HF5 and Et3N), which is not very basic.
In our laboratory, we are developing a program to synthesize cr,B aminofluorosugars by nitrogen atom participation6 and a moderated neutral nucleophilic fluorinating reagent was needed because many carbohydrates are very sensitive to basic or acidic conditions. For example we wanted to obtain a 3,6difluoroglucosamine derivative 1 in one step starting from 1 (scheme). When Et3N.3HF was used, compound 2 was isolated in good yield, but the fluorinating reagent was not nucleophilic enough to give 2 ;
other reagents such as R4N%IF2-were too basic and led to tars due to the axial 4-OMs (elimination of MsOH gave a very unstable enamine). 2 was synthesized by treatment of 2 with Et4N%IF2-(the 4-OMs is equatorial and the elimination is unfavoured), but we found that on addition of Et3N to the Et3N.3HF complex it was possible to obtain 2 in one step starting from 1. in good yield.' In the literature various proportions of amines and HF have been previously describeda. but the previous studies did not attribute any difference of selectivity to the stoichiometry of the system, so we tried to understand why Et3N addition to the Et3N.3HF complex enhanced its nucleophilicity. We supposed that a new complex was formed and two possibilities were considered :
Et3N.3HF t 2 Et3N -