Fluorination reactions, hydroxyl group conversion

In conclusion, it appears that conformational factors play the most important role in nucleophilic substitution with fluorine at C 2 of the sugar moiety but are not necessarify crucial in a similar nucleophilic displacement at C 3. It was reported that nucleophilic displacement of the 3 -hydroxyl group in 9-(2-deojgr-6-D-xylofuranosyI)adenine with DAST was completed Avithin 1 hour, whereas the same reaction with the 2 -hydroxy group of 9-(3-deoxy-6-D-arabinofuranosyl)adenine required 14 hours. This reflects an unfavorable electronic factors at C 2 due to the proximity of the anomeric center. Also, steric factors are in favor of the S 2 conversion of nucleoside 87 with DAST, since nucleophilic attack fi-om the a-side of the nucleoside is much more efficient than that from the B-side. Therefore, even unfavorable C 3 -endo conformation of 87 did not cause elimination and 3 -a-fluoro substituted derivative 90 was obtained in good yield. In contrast, displacement of the 2 -hydroxyl group in the ribo configuration, such as conversion of 25 to 27,31 to 35, or 41 to 42, is much more difficult, which requires the favorable C 2 -endo conformation in order to prevent undesired elimination. 

The antitumor chemotherapy agent clofarabine (104) sports halogen on the purine as well as on the sugar. The major portion of the synthesis involves preparation of the requisite fluorine-substituted furanose (101). The sequence begins with the conversion of the only free hydroxyl in allofuranose bis(acetonide) (95) to its tosylate (96). This group is then displaced by fluorine in its reaction with potassium fluoride to afford... 

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