Diethylaminosulfur trifluoride , fluorination reactions

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). 

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>. 

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. 

Sulfides are selectively fluorinated a to the sulfur atom via a reaction similar to the Pummerer rearrangement (Table 2). The fluorination wa.s originally achieved by the direct fluorination of sulfides with xenon difluoride.This reaction is proposed to occur by initial oxidative fluorination of the sulfide to give an unstable sulfur(IV) difluoride of type 1, followed by loss of hydrogen fluoride to give intermediate 2, followed by fluorine transfer to give the a-fluoro sulfide. This fluorination has also been achieved with diethylaminosulfur trifluoride (DAST) in the absence or presence of catalytic amounts of antimony(III) chloride (see Vol. ElOa, pp 421-423). ... 

The reaction of a-fluoro-/ -hydroxy-a-phenylsulfanyl esters 4, which can be readily synthesized from aldehydes and ethyl bromofluoroacetate, with diethylaminosulfur trifluoride leads to the formation of a,a-difiuoro-/I-phenylsulfanyl esters 5.247 Instead of the expected substitution of the -hydroxy group by fluorine, a rearrangement via an episul Ionium ion and addition of a fluoride ion a to the ester function gives the a,a-difluorinated product 5. The reaction proceeds under mild conditions with moderate to good yields. In the case of ethyl 2-fiuoro-3-hydroxy-3-phenyl-2-(phcnylsulfanyl)propanoate only the nonrearranged product ethyl 2.3-di-fluoro-3-phenyl-2-(phenylsulfanyl)propanoate was isolated. 

Although the majority of radiopharmaceuticals labeled with fluorine-18 have been prepared using nucleophilic fluorination reactions, in a few instances the application of electrophilic fluorination reactions has proved quite suitable. The most significant limitation of electrophilic 18F-fluorinations is the relatively low specific activities (less than lOCi/mmol) commonly obtained for final products. This is a result of the fact that electrophilic 18F-fluorination reagents (perchloryl fluoride, acetyl hypofluorite, xenon difluoride, A-fluoro-zV-alkylsulfonamides, diethylaminosulfur trifluoride) are prepared in low specific activity from 18F-labeled fluorine gas, which in itself produced in a carrier-added fashion. A second drawback of electrophilic fluorination is that the maximum radiochemical yield obtainable is 50%, as only one of the two fluorine atoms in fluorine gas can end up in the product (or, for preparation of electrophilic reagents such as acetyl [18F]hypofluorite, the maximum yield of preparing the reagent from [18F]F2 is 50%). 

Diethylaminosulfur trifluoride (DAST) is one of the most commonly used reagents for stereospecific replacement of hydroxyl group by fluorine, which usually proceeds with the inversion of stereochemistry. Scheme 12.16 shows two examples. The reactions of 107 and 111 with DAST provide fluorides 108 and 112 in moderate yields, both of which are precursors of Lodenosine 100. 

Diethylaminosulfur trifluoride, 6, 183-184. Detailed directions are available for preparation of this fluorination reagent and for its reaction with p-nitrobenzyl alcohol to form p-nitrobenzyl fluoride (67% yield). ... 

Fluorinated compounds exhibit an enhanced metabolic stability and are therefore valuable compounds in the pharmaceutical chemistry. Dialkylaminosulfur trifluoride derivatives (Figure 6.1) are common commercially available nucleophilic fluorinating agents, but are thermally instable and need careful handling. Therefore, reactions vith diethylaminosulfur trifluoride (DAST, 1) or bis(methox-yethyl)aminosulfur trifluoride (Deoxo-Fluor , 2) are suitable for processing in microfluidic devices. 

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