Epimerization fluorine

MeCN, r.t., 24 h) gave, respectively, a mixture of fluorinated derivatives 287 (67%) and 290 (6%), and 290 (54%) and 287 (11%). In each case, the minor products were formed by C-5 epimerization of the starting compounds prior to the displacement, followed by fluorination. Reduction (NaBHJ of 287 and 290, followed by hydrolysis, gave an anomeric mixture of 5-deoxy-5-fluoro-L-idofuranose (from 287) and 5-deoxy-5-fluoro-D-glucofuranose... 

The reaction of 3/3-acetoxy-5a-cholest-8(14)-en-7-one with EtjAlCN was the key reaction in a synthesis of cholestanes containing an oxygenated 14a-substi-tuent. Cholest-4-en-3-one reacted smoothly with KCN-acetone cyanohydrin in benzene or acetonitrile containing 18-crown-6 to give the epimeric 5-cyano-cholestan-3-ones. An 11 -hydroxy-group increased the proportion of a-epox-ide produced in the reaction of 3-oxo-A -steroids with H202-0H . A 9a-fluorine substituent also influenced the stereochemistry of the reaction products and a... 

The beneficial effect of fluorine atoms on hydrolytic stability has been demonstrated with synthetic prostaglandin (SC-46275). This compound possesses an antisecretory activity that protects the stomach mucous membrane. However, its clinical development was too problematic because of the instability of the tertiary allyl alcohol function in acidic media (epimerization, dehydration, etc). A fluorine atom has been introduced on the C-16 methyl to inhibit the formation of the allylic carbocation (Figure 4.39). The fluoroanalogue possesses the same biological activity but does not undergo any degradation or rearrangement, and it epimerizes only slowly. 

Interesting solutions to the spontaneous epimerization of C2-substituted malonyl residues, to provide configurational stability, were explored independently by Dal Pozzo and Laurita 111 and Abouabdellah and Welch. 30 Replacement of the C2 hydrogen in C2-alkyl-substituted malonyl residues by either methyl 111 or fluorine 30 stabilized the configurational integrity of the C2 chiral center in the malonyl derivatives. 

This fluorine-containing, oxidation-resistant alcohol is best oxidized by the Pfitzner-Moffatt reaction, using dichloroacetic acid as catalyst. Observe the use of toluene, instead of carcinogenic benzene, as solvent. A Swern oxidation was not reproducible, and caused substantial epimerization of the isobutyl side chain. Collins oxidation was successful, but ... 

In the presence of amido substitution at the adjacent center, epimerization with complete lack of fluorination has been observed, e.g. in the case of cromakalim (14). ... 

Fluorinated 2-isoxazolines have been obtained stereoselectively from 2-(polyfluoroacyl)cycloalkanones and hydro-xylamine in the presence of catalytic BF3-OEt2 <2002HCA1960>. Enones 507 derived from disaccharides melibial and gentobial reacted with 2 equiv of hydroxylamine to afford isoxazolines 508 as an inseparable epimeric mixture in 80-83% yield. By treatment with -toluenesulfonic acid, compounds 508 underwent dehydration to give isoxazole derivatives 509 in high yields (Scheme 117) <2004T6453>. 

It is possible that this mechanism may be limited to nucleophilic activation by fluoride anion. Indeed, Muetterties and Mahler (1965) have demonstrated that fluorine stabilizes the hexacoordinate state. However, Corriu et al. (1984a) imply more general application. The nucleophilic activation hypothesis may be of relevance to the epimerization reactions discussed on p. 155. 

The preparation of a stabilized monofluorobenzyl carbanion by means of a remote homochiral sulfinyl group and its completely stereoselective reactions with //-p-tolylsulflnylimines have been described. The use of these reactions followed by the simultaneous removal of both chiral auxiliaries with f-BuLi, which occurs without epimerization at the benzylic position, provides the quickest entry to enantiomerically pure /3-fluorinated /3-phenylethylamines. 

There has been a fuller account given of the reactivity of pyrimidine 2 -deoxy-2 -methylene nucleosides and their use in making 3 -amino-2, 3 -dideoxy-2 -methylene nucleosides (sec Vol. 26, p. 240-241). 29 Reaction of 2 -deoxy-2 -methylene-5 -0-trityluridine with DAST gave, after deprotection, the fluorinated systems 103 and 104 the 3 -q>imer of 103, together with 104, was produced when the epimeric starting material was used, and cytidine analogues were prepared from the uridine derivatives. ... 

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