Benzyl fluorides, synthesis

The synthesis of benzyl fluorides from benzyl halides is problematic due to the tendency to undergo Friedel Crafts reactions.The fluorination of benzyl bromide with thallium(l) fluoride gives impure benzyl fluoride and attempts to fluorinate benzyl halides with anti-mony(III) fluoride, silver fluoride, and potassium fluoride were all unsuccessful. Benzyl fluorides with substituents which deactivate the aromatic system towards Friedel-Crafts reactions are successfully obtained through halogen exchange with mercury(II) fluoride (Table... 

The Mukaiyama condensation method was also utilized in the synthesis of several antibiotics and related bioactive substances. These syntheses include apramycin, using 4-azido-2,3,6-tri-(P-benzyl-4-deoxy-) -D-glucopyranosyl fluoride (prepared from the corresponding a-D-glucopyranosyl chloride by the AgF method ) avermectin B , using protected sugar derivatives of oleandrosyl fluoride (a-L-Ole-F) and 0-(a-L-01e)-(1 4)-a-L-0le-F (both... 

The Noyori procedure was applied to a total synthesis of baiyunoside, a sweet principle, using 2,3,4-tri-<9-benzyl-D-xylopyranosyl fluoride (18 see Table 1), and a synthesis of glycotriosyl ceramide. A model experiment for the synthesis, using 18, showed a solvent dependence for the a ratio of the products. In this case, the use of acetonitrile, oxolane, or ether gave the a anomer (1,2-a.v), and the use of toluene or hexane gave the P anomer (1,2-trans), preponderantly. 

Preparation of 2-fluorofuranoses is also important in relation to the synthesis of biologically active 2 -fluoro derivatives of nucleosides (see Section 111,4). Su and coworkers prepared the 2-triflates 236 and 239 through acid-catalyzed methanolysis of 3,5-di-O-benzyl-1,2-(9-isopropylidene-a-D-ribofuranose [to give 235 (major) and 238] and subsequent triflylation. On treatment with fluoride ion, the anomer 236 afforded exclusively the furan derivative 237, whereas the a anomer 239 gave the 2-fluoro compound 240... 

An efficient method for the generation of oquinodimethanes via desilylation reaction involves treatment of a 2-[(trimethylsilylmethyl)benzyl]trimethylarmnonium iodide with fluoride ion (equation 31)64. This reaction was applied by Saegusa and coworkers for the synthesis of estrone in which an intramolecular Diels-Alder reaction of an o-quinodimethane, generated in situ, served as the key reaction (equation 32)65. 

This method was also found to be applicable to the synthesis of 1,2-cis glycofur-anosides. 2,3,5-Tri-O-benzyl-P-ghicofuranosyl fluoride 17 was found to react with various alcohols, including sterically hindered t-butyl alcohol, in the presence of SnCl2-TrC104 (Tr = Ph sC), thereby affording a good route to 1,2-cis furanosides that are difficult to obtain by other means (Scheme 2.6, Table 2.2) [7]. 

An important application of these precursors is the asymmetric synthesis of aminoacids, the key step being an enantioselective benzylation using a chiral auxiliary (route A, Scheme 25) [155] or a chiral phase transfer catalyst (PTC) [156] (route B, Scheme 25). This latter approach avoiding the use of dry reagents is particularly adapted to automated synthesis and enables the production of more than 7.4 GBq (200 mCi) of [6- F]fluoro-L-DOPA from 55.5 GBq (1.5 Ci) of starting [ F] fluoride [157]. 

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