Alcohols reaction with DAST

It has been shown in a related case that the hydrolysis of an intermediate dihydrooxazole ring is the reason for this reaction.Hence, the actual mechanism by which fluorination takes place in reactions with DAST mainly depends on the structure of the alcohol. In the following subsections only recent material is considered for material published before 1985, see ref 38. 

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). 

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... 

In addition to the perfluoroalkylzinc compounds, the zinc reagent formed from 1,1,1-trifluorotrichloroethane has received considerable attention. This zinc compound was first reported as a stable ether complex [56]. Later, the DMF complex was isolated and the structure was determined by X-ray diffraction and shown to be monomeric [57] (equation 50). This zinc reagent undergoes a variety of functionalization reactions, and some typical examples are illustrated in Table 2 [47, 58, 59, 60, 61] The alcohol products (Table 2) can be converted to AiCF=CXCF3 (X = Cl, F) by further reaction with diethylaminosulfur trifluoride (DAST) and l,8-diazabicyclo[5 4.0]undec-7-ene (DBU) [60]... 

Another useful modification of this reagent is the reaction of CF3CCI3 with zinc and DMF in the presence of AICI3 [60, 63] (equation 53). The alcohol product can be treated subsequently with DAST, thionyl chloride, or phosphorus chlorides to afford the allyl substitution product regio- and stereoselectively [66] (equation 54). 

Et2NSF3, DAST). In this reaction, an alcohol displaces a fluoride of DAST resulting in an activated intermediate, which in turn is displaced by the liberated fluoride (Scheme 3.2c).11 A gem-difluoride is formed when a kptone or aldehyde is treated with DAST. 

Secondary alcohols give lower yields of fluorinated products (see Table 8) than primary alcohols, which is probably due to side reactions such as elimination and rearrangement. As discussed (vide supra) these undesirable reactions occur with fluoroalkylamine reagents to a greater extent than with DAST, which is therefore preferable in most cases. 

SF4 and diethylaminosulfur trifluoride (DAST) give alkyl fluorides not only from tertiary and secondary, as with HF, but also from primary alcohols (equation 36). Reactions with gaseous, corrosive SF4 (b.p. -38 °C) usually require temperatures of 20-100 C. The special equipment needed for reactions with toxic gases under pressure make the use of SF4 inconvenient. The introduction of DAST has removed the handling problems. DAST is a liquid reagent made from SF4 and trimethylsilyldiethyl-... 

In 2008, important developments on the fluorination with DAST on laboratory scale were presented by Gustafsson et cd. [5]. The authors utilized a commercially available microfluidic Syrris FRX system (www.syrris.com) with HPLC pumps and PTFE tubings with an ID of 1 mm (V= 16ml) for the development of a DAST deoxofluorination protocol for a variety of substrates, for example, alcohols, lactols, aldehydes, and carboxylic adds (Figures 6.6 and 6.7). One of the main features of the protocol is the short residence time of 16 min. The reactions were run in dichloromethane and superheating to 70 °C under a pressure of 75psi (5.1 bar) allowed for shortened reaction time. As described... 

Primary and secondary hydroxyl groups can be fluorinated by reaction with di-ethylaminosulfiir trifluoride (DAST) [103]. The reaction of asymmetric secondary alcohols produces inversion of the configuration. Thus, the reaction of the protected diacetone allose with DAST, followed by removal of the protective groups, gives 3-deoxy-3-fluoro-D-glucose [104] (reaction 4.100). 

Finally, paraherquamide A tl84). a tertiary alcohol, provided exo-olefin 185 when treated with DAST [(diethylamino)sulfur trifluoride]. Subsequent reduction of the oxindole system, followed by dihydroxylation of the exocyclic double bond and cleavage of the resultant 1,2-diol 186, converted into ketone 187. Concluding reaction of 187 with... 

Highly varied stereochemical outcomes have been obtained in the reactions of DAST with secondary alcohols. Thus, although products of partial or complete racemization through ionic or ion-pair mechanisms have not been widely observed, the usual steric course is complete inversion or complete retention at the reaction center. An example is the formation of (—)-2-fluorooctane (97.6%... 

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