DAST •»

Halide derivatives may be fluorides, chlorides, or bromides. Fluorides are best prepared by the reaction of hydroxy groups with (diethylamino)sulfur trilluoride ( DAST M. Sharma, 1977) or of glycosyl thioethers with DAST/NBS (K.C. Nicolaou, 1990 B). The other halides are usually only introduced at the glycosidic position, where treatment with hydrogen chloride... 

When the 2-hydroxy group of a monosaccharide reacts with (diethylamino)sulfur trifluoride (DAST), quantitative and stereoselective rearrangements are observed (K.C Nico-laou, 1986). This reaction may simultaneously introduce fluorine to C-1 and a new oxygen, sulfur, or nitrogen residue to C-2 with inversion of configuration. 

The high cost of SF and the incomplete use of fluorine justify its use only for inaccessible ben2otrifluorides. The related Hquid S—F reagent, (diethylarnino)sulfur trifluoride (DAST), (C2H )2NSF2, also effects similar transformations with aromatic carboxyhc acids (108). 

Dastes indicate unavailaLle states blanks indicate no data. 

Diethylaminosulfur trifluoride (DAST) reacts with epoxides to give com plex mixtures in which vicinal as difluorides, gemmal difluorides, and bis(2-fluoroalkyl) ethers are the mam components I6 (equations 16 and 17)... 

Table 6a. Fluorination of Primary Alcohols with Diethylamiiiosulfur Trifluoride (DAST)...

Huonnations with DAST proceed with high chemoselectivity In general, under very mild reaction conditions usually required for the replacement of hydroxyl groups, other functional groups, including phenolic hydroxyl groups [112], remain intact This provides a method for selective conversion of hydroxy esters [95 97] (Table 6), hydroxy ketones [120, 121], hydroxy lactones [722, 123], hydroxy lactams [124] and hydroxy nitriles [725] into fluoro esters, fluoro ketones, fluoro lactones, fluoro lactams, and fluoro nitnles, respectively (equations 60-63)... 

CL Amino-(i-hydroxy esters in which the amino group is protected as a 4,5 diphenyl-3-oxazohne-2-one moiety undergo fluontiation with DAST to give the corresponding (1 fluoro compounds as the main products along with the dehydrated compounds [/2(5] (equation 64)... 

Dehydration to olefins, which sometimes accompanies the reaction of alcohols with DAST [95, 108], is seldom as extensive as with a-fluoroamines (FAR and 1,1,2,3,3,3 hexafluoropropyldiethylamine) but occurs in a few cases to the exclusion of fluonnation, thus, 9a-fluoro-11-hydroxysteroids give 9a fluoro-A -steroids [127, 128] Dehydration accompanied by Wagner-Meerwein rearrangement occurs during the fluonnation of testosterone [129] Intermolecular dehydration to form ethers in addition to fluorides is observed in the reaction of benzhydryl alcohols [104] (Table 6)... 

Carbocation rearrangements occur in the reactions of some secondary alco hols with DAST, thus isobutyl alcohol gives a mixture of isobutyl fluoride and tert-hxAy] fluonde [95] (Table 6), and both bomeol and isoborneol rearrange to the same 3-fluoro-2 2,3-tnraethylbicyclo[2 2 IJheptane (72-74%) accompanied by camphene [95]... 

Skeletal rearrangements in volving a ring size change are observed in reactions of DAST with some cyclic alcohols [131, 134, 755] (equations 69 and 70). 

On the other hand, as a result of participation of a neighboring group, complete or predominant retention of configuration takes place in many reactions of hy-droxylic compounds with DAST A number of examples have been reported in the field of steroids [727, 729], m the conversion of vitamins D into fluoro vitamins D [745], and in the fluormation of liquid crystals [146] (equation 72]... 

Reactions of polyhydroxyl compounds such as carbohydrates with DAST lead to replacement of one or two hydroxyl groups by fluorine, more fluorine atoms are not introduced even when a large excess of the reagent is used [132, 139, 147] Although diethylaminosulfur tnfluonde (DAST) is the most popular, other dialkylaminosulfuranes, such as diisopropylamino- [95] pyrrolidino [95 109 /27], dimethylamino- [148], piperidino- [148] and particularly morpholinosulfur trifluonde [148,149, ISO], are also used as fluonnating agents to convert alcohols into fluorides... 

Morpholinosulfur trifluoride is more thermally stable and therefore safer to handle than DAST and gives a slightly higher yield of the fluoride in the fluorination of cyclohexanol [95, ISO] Both solvent and conformational effects are pronounced in the fluorination of cyclohexanols [550] The chiral (S)-2-(methoxymethyl)pyr-rolidin-l-ylsulfur tnfluonde is an effective enantioselective fluorodehydroxylating agent [ISI]... 

Bis(dialkylamino)sulfur difluorides, RjNSFaNRj, albeit less reactive than DAST, also substitute hydroxyl groups with fluorine [95, 97 /52]... 

Both aliphatic and aromatic carboxylic acids are converted to their fluorides by FAR [78, 79, by the Ishikawa reagent [S/], and by fluoroaminosulfuranes such as DAST [128, 166] and its analogues [128]... 

Because aldehydes react with aminofluorosulfuranes more readily than ketones, keto aldehydes can be selectively fluorinated at the formyl group [94, 183] Haloacetaldehydes react with DAST to give bis(l-fluorohaloethyl) ethers as the only or main products [170] (equation 96)... 

Most aliphatic [95, 184, 185, 186, 187], aromatic [95 186,188], md heterocyclic [189,190] ketones react with DAST in the usual way to give geminal difluoro derivatives Fluonnation of cycloaliphatic ketones, in particular, is often accompanied by a spontaneous dehydrofluorination to form considerable amounts of... 

On treatment with DAST, 4-kelo carboxylic acids undergo cyclization to form Y-fluorolactones almost quntitatively [192] (equations 98 and 99)... 

Numerous examples of application of DAST for replacement of carbonyl oxygen by fluonne have been reported in the field of carbohydrates [193,194,195] and particularly in the field of s/eroidi [141, 142, 183, 196, 197, 198, 199]... 

Chemistry of Organic Fluorine Compounds II DAST, CHCla... 

On treatment with DAST, keto esters undergo oxidative fluorination- ethyl acetoacetate and DAST in W-methylpyrrolidone give a 48-58% yield of a mixture of equal parts of ethyl cis- and trans-2,3-difluoro-2-butenoate [200] (equation 100)... 

Carboxylic acids react both with fluoroaminosulfiiranes such as DAST and with sulfur tetrafluonde. Whereas DAST converts the acids to acyl fluorides only, sulfur tetrafluonde further fluorinates the primarily formed acyl fluorides and ultimately converts the carboxyl group to a trifluoromethyl group. 

The transformation of an ester carbonyl group to a difluoromethylene group, which IS usually difficult to perform, can be accomplished by conversion to the thiaesier followed by treatment with diethylaminosulfur trifluoride (DAST). A vanety of ester types react efficiently, although the reaction fails with lactones. Remarkably, trimethylsilylmethyl esters carry through the proeedure with the silyl group intact [13] (equation 17). 

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