Diethylaminosulfur trifluoride , fluorination

Table 6b. Fluorination of Secondary Alcohols with Diethylaminosulfur Trifluoride (DAST)...

Dialkylaminosulfur trifluorides, - exemplified by diethylaminosulfur trifluoride (Et2NSF3, DAST), were introduced into carbohydrate chemistry as fluorinating agents by Sharma and Korytnyk, and they can be... 

A-Acetyl-9-deoxy-9-fluoroneuraminic acid (591) was prepared by treatment of a protected 6-hydroxyl precursor with A, A-diethylaminosulfur trifluoride (DAST) or through condensation of 2-acetamido-2,6-dideoxy-6-fluoro-D-mannopyranose with potassium di(/ >r/-butyl) oxaloacetate. Compound 591 is a substrate for cytidine monophosphate (CMP)-sialic acid synthetase, giving rise to CMP-5-A-acetyl-9-deoxy-9-fluoroneuraminic acid, which is cytotoxic against tumor cells. 5-A-Acetyl-3-fluoroneuraminic acids 592-594 were prepared through fluorine (or acetyl hypofluorite) addition (in AcOH) to methyl 5-acetamido-4,7,8,9-tetra-0-acetyI-2,6-anhy-dro-2,3,5-trideoxy-D- /ycm>D- a/arto-non-2-enopyranosate. Compound 592 was found to be a potent neuraminidase inhibitor. 

Displacement of the 3-hydroxyl group of 74 was carried out with Et2NSF3 (DAST) (DAST - diethylaminosulfur trifluoride) in dichloromethane. The expected fluorinated product 75 on treatment with aqueous perchloric acid led to regioselective epoxide ring opening to give 76, which on treatment with hydrazine hydrate at 100 °C for 18 h yielded 3,4-dihydroxy-8-oxo-octahydropyridazino[l,6-r/][l,2,4]triazine-l-carboxylic acid phenylamide 77 (Scheme 3) <1997T9357>. 

A comparison of various fluorinating agents in the preparation of fluoride 13, i.e. (2-chloro-1,1,2-trifluoroethyl)diethylamine and diethylaminosulfur trifluoride (R = H), tetrafluoro(phen-yl)-A5-phosphane (R = TMS), and potassium fluoride (R = Ts), has shown that the highest stereoselectivity is achieved with potassium fluoride and (2-chloro-l,1,2-trifluoroethyl)-diethylamine.19 The fluorination with tctrafluoro(phenyl)-7.5-phosphane proceeds, at least in part, via a carbocation and with a relatively low enantioselectivity.15... 

The most useful fluorinations that can be brought about with it are the same as those brought about by sulfur tetrafluoride and diethylaminosulfur trifluoride.19 20 Examples are the formation of 1 and 2,9 3,21 4,22 5,9,23 and 69 24 (note that only the carbonyl reaction requires the presence of a Lewis acid). 

M. Hudlicky, Fluorination with diethylaminosulfur trifluoride and related aminofluoro-sulfuranes, Org. React. 35 513 (1988). 

M. G. Straatmann and M. J. Welch, Fluorine-18-Iabeled diethylaminosulfur trifluoride (DAST) A fluorine-for-hydroxyl fluorinating agent, J. Nucl. Med. 78 151 (1977). 

The commercially available diethylaminosulfur trifluoride, Et3NSF, (DAST), was shown to be a particularly convenient fluorination reagent (for a review, see [259]). The sequence shown here was used for the preparation of a,a-difluoroethers [138],... 

Diethylaminosulfur trifluoride (DAST, Et2NSF3) a-cleaves cyclic ketoximes to give fluorinated carbonitriles,47 e.g. (27)—> (28). Two mechanisms are proposed, one for substrates with substituents that can stabilize an a-carbocation, and an iminium cation route for ketoximes without such groups. 

The displacement of 3 -hydroxyl group of 270 with fluorine was attempted with diethylaminosulfur trifluoride (DAST) but the reaction resulted in the formation of a nonfluorinated product 101 (Scheme 61) <1997T9357>. 

D. J. Baillargeon and G. S. Reddy, Novel 2,6-anhydro-/l-D-hexopyranosyl fluorides by fluorination of l,6-anhydro-/j-D-hexopyranoses with diethylaminosulfur trifluoride, Carbohydr. Res., 154 (1986) 275-279. 

The above-discussed methods are mainly used for the synthesis of chloro, bromo and iodo sugars. A different approach has to be taken when a deoxyfluoro sugar derivative is required, and the most commonly applied reagent for direct fluorination is diethylaminosulfur trifluoride... 

The usual reaction of diethylaminosulfur trifluoride (DAST) with a carbonyl group is the replacement of carbonyl oxygen by two atoms of fluorine, thus generating geminal difluorides. 

Ethyl acetoacetate reacts in its enol form with one molecule of diethyl-aminosulfur trifluoride. The hydroxyl group is replaced by fluorine, and ethyl a-fluoroacetoacetate is formed. This compound reacts again in its enol form with another molecule of diethylaminosulfur trifluoride to give ethyl a,P-difluorocrotonate as a mixture of equal parts of E- and Z-isomer. 

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