Benzylic fluorine, elimination

Whereas fluorine in saturated straight-chain aliphatic compounds is not susceptible to nucleophilic replacement, its reactivity towards sulfur nucleophiles is markedly enhanced by an adjacent aromatic ring (e.g., in benzyl fluorides) as well as by double bonds. Thus, perfiuoroalkcncs are readily attacked by nucleophiles their addition-elimination reactions are discussed in Vol. ElOb/Part 1, p618tf. 

The ability of fluoro-2 -phosphanes to transform silyl ethers into fluorides was first observed during a study of the reactions of phosphorus pentafluoride and its derivatives R PF5 (n = 1, 2, 3 R = hydrocarbon group) with trimethylsilyl ethers. Subsequently, this reaction was proposed as a new method for the preparation of C-F compounds from silyl ethers or silicic acid esters with fluoro-A -phosphanes. Pentafluorophenyl-substituted fluoro-A -phos-phanes were found to react similarily, Other workers found that tctrafluoro(phenyl)-A -phos-phane. which was chosen as the most convenient reagent with regard to reactivity and stability, gave considerable amounts of elimination products, especially with primary and cyclic alcohols. Good yields of fluorinated products are obtained when stable carbocations can be formed at the site of substitution, such as in tertiary alcohols, but 2-phcnylethanol. benzyl alcohol and diphcnylmethanol, on the other hand, give only poor yields of fluorinated products ethers and polymers are the main products. ... 

Since fluorine-containing organic compounds are more acidic than the hydrocarbon analogs, we started to study benzylic compounds that have trifluoromethyl groups and chlorine atoms to increase their acidity. Two compounds with rates of protodetritiation similar to that for 9-PhFl-9-t were of interest QH5CH(CF3)2 1 and P-CF3QH4CHCICF3 [P-CF3-2]. Measurement of the pfQ values for 1 and P-CF3-2 are not possible in solution due to elimination of a y9-fluoride. However, Mishima has been able to obtained their gas phase acidities, AG =... 

Benzyl-3-sulfolene was found to be inert to alkylation, even at elevated temperatures, probably as a result of steric hindrance of the carbanion generated in the 2-position. Attempts at alkylation of 3-trifluoromethyl-3-sulfolene resulted in decomposition of starting material, most likely due to elimination of a fluorine atom situated 7 to the carbanion. 

The nucleophilic exchange of one bromine atom in l-benzyl-3,5-dibromo-l,2,4-triazole 21 with fluorine under the action of CsF followed by the photoinitiated elimination of the benzyl protective group led to the formation of 3-bromo-5-fluoro-lH-1,2,4-triazole 22 in 59 % overall yield. The alkylation of this substrate gave l-alkyl-3-fluoro-l,2,4-triazoles for the first time. Both bromine atoms were substituted to provide the corresponding difluoro derivative 24 under the same reaction conditions, but using l-(3,5-dimethoxybenzyl)-3,5-dibromo-l,2,4-triazole 23 as substrate for fluorination [32]. 

Since TASF and DAST were reported as efficient reagents in fluorination of sugars and nucleosides we studied if a good leaving group at C-2 of a purine nucleoside such as 8 could be displaced with fluorine by these reagents. Thus, we thesized 3, 5 -di-0-benzyl-2 -0-triflyl-l-benzylinosine for TASF treatment As depicted in Scheme 3 the 3, 5 -0-(l,l,3,3-tetraisopropyl)disiloxanyl-l-benzylinosine (17) was treated with dihydropyran (DHP)/TsOH and then desilylated with EtjNHF-THF to obtain 19. Ben lation of 19 followed by 2 -0-deprotection and triflylation afforded 20-22. Finally, when 22 was treated with TASF, only elimination products 23 and 24 were isolated. No traces of F-ara-H were detected in the reaction mixture. 

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