Deoxo-Fluor trifluoride

Air Products, USA., has developed bis-(2-methoxy ethyl) aminosulphur trifluoride as a cost effective, safe, stable fluorinating agent, made by reaction of di-2-methylethylamine with sulphur tetrafluoride and trade named Deoxo-Fluor, which replaces the more temperamental diethylaminesulphur trifluoride. Thus, p-phenylethyl alcohol was converted to P-phenylethyl fluoride in 85% yield (Stinson, 1999). 

Dialkylaminosulfur trifluorides are widely used as a safe substitute for SF4 in the replacement of oxygen by fluorine in many types of organic compounds, for example, converting alcohols to fluorides, or aldehydes and ketones to gem-difluorides. The most familiar of these reagents is DAST, while an increasingly popular one (considered safer to use than DAST) is bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor Reagent) (Scheme 7.15). 

As described previously, thiazolines are versatile intermediates to thiazoles. In addition, thiazoline rings are structural motifs found in numerous natural products. Among a variety of methods for the construction of thiazolines, the cyclodehydration protocol is perhaps most popular. Bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor) is used as the cyclo-dehydrating agent for the conversion of 3-hydroxy thioamide 60 to the bis(thiazoline) 15 <04H(63)773>. A more recent protocol for the cyclodehydration of P-hydroxy thioamides to thiazolines involves pyridine-buffered phosphorus oxychloride as exemplified by the formation of 62 from 61 <04JA12897>. 

Wipf and co-workers developed an efficient one-pot process to prepare a variety of highly functionalized 2-substituted 4-oxazolecarboxylic acid esters 39. The starting (3-hydroxyamides 1588 were cyclodehydrated using Deoxo-fluor (bis(2-methoxyethyl)aminosulfur trifluoride) or DAST (diethylaminosulfur trifluoride) to afford intermediate oxazolines 38, which were oxidized in situ with B1CCI3/ DBU to afford 39 (Scheme 1.404). DAST was found to be preferable with serine-derived p-hydroxyamides, whereas Deoxo-fluor was more useful for threonine derived p-hydroxyamides. 

Carboxylic acid 125 was coupled with ethanolamine or L-serine methyl ester hydrochloride in the presence of EDCI, HOBt, and EtsN to afford the corresponding p-hydroxy amides, which were cyclized using bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor) to afford oxazolines (149 and 150, Scheme 24) [56, 57]. Oxazoline 150 was converted to oxazole 151 in 80% yield by treatment with bromotrichloromethane and DBU, conditions which did not lead to epimerization at C-8 [57], A variety of oxadiazoles (152-158) have been produced in 10-56% yield by treating carboxylic acid 125 with appropriate amidoximes in the presence of EDCI and HOBt followed by heating in toluene (Scheme 24) [44, 57, 58]. These conditions led to some epimerization at C-8, necessitating purification by HPLC. Carboxylic acid 125 was treated with either (2-hydroxybenzyl)triphenyl- or (2-thiobenzyl)triphenyl phosphonium bromide in the presence of CDMT and EtsN to afford the benzofuran (159) and benzothiophene (160) products in 26 and 35% yield, respectively (Scheme 24) [58]. 

Treatment of polymer-supported ot-sulfonyloxy ketones with thioamides in the presence of potassium carbonate affords 1,3-thiazoles (Scheme 19), 2-Alkylbenzothiazole derivatives have been obtained by palladium-catalysed intramolecular cyclization of iV-(o-bromophenyl)thioamides (Scheme 20). p-Hydroxythioamide cyclodehydration reaction has been carried out using Deoxo-Fluor reagent, [Ai5(2-methoxyethyl)amino]sulfur trifluoride, to afford 4,5-dihydro-1,3-thiazoles (Scheme 21). ... 

Deoxo-Fluor = Bis(2-methoxyethyl)aminosulfur trifluoride DIEA = Diisopropylethylamlne... 

Deshmukh et al. demonstrated that triphosgene can also be used to prepare dialkylcar-bamoyl azides from tertiary amines and sodium azide. Alternatively, acyl azides (e.g. 303) can be converted via a one-step procedure from carboxylic acids using bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor) (Scheme 3.46). ... 

Bi X (2006) Deoxo-Fluor (bis(2-methoxyethyl)aminosulfur trifluoride) an advanced nucleo-phUic fluorinating reagent in oiganic synthesis. Synlett 2515-2516... 

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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