Deoxo-Fluor

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). 

A direct catalytic conversion of esters, lactones, and carboxylic acids to oxazolines was efficiently achieved by treatment with amino alcohols in the presence of the tetranuclear zinc cluster Zn4(0C0CF3)60 as catalyst, essential for condensation and cyclodehydration reactions. For example, the use of (5)-valinol allowed the easy synthesis of oxazolines 125 and 126 in satisfactory yields <06CC2711>. A one-pot direct preparation of various 2-substituted oxazolines (as well as benzoxazoles and oxadiazoles) was also performed from carboxylic acids and amino alcohols (or aminophenols or benzhydrazide) using Deoxo-Fluor reagent <06TL6497>. 

CH3OCH2CH2)2NSF3 r CH2CI2, -20°C, 0.5-2 h Deoxo-Fluor Scheme 21... 

Deoxo-Fluor reagent is a versatile reagent for acyl fluoride generation and subsequent one-flask amide coupling. Georg and coworkers have explored the utility of this reagent for the one-flask conversion of acids to hydroxamic acids and Weinreb amides (Scheme 105) ". ... 

Bis-(2-methoxyethyl)aminosulfur trioxide (Deoxo-Fluor) has also been used in place of DAST. Deoxo-Fluor may have the advantage of increased thermal stability. A comparison of the two reagents for the cyclization of several peptidyl p-hydroxy amides has been reported (Table 8.13). 

TABLE 8.13. COMPARISION OF DAST AND DEOXO-FLUOR FOR CYCFIZATION OF PEPTIDYF P-HYDROXY AMIDES"... 

TABLE 8.13 COMPARISON OF DAST AND DEOXO-FLUOR FOR CYCLIZATION OF PEPTIDYL P-HYDROXY AMIDES, 372... 

Tunoori, A. R., White, J. M., Georg, G. I. A One-Flask Synthesis of Weinreb Amides from Chiral and Achiral Carboxylic Acids Using the Deoxo-Fluor Fluorinating Reagent. Org. Lett. 2000, 2, 4091-4093. 

Scheme 8.3 Reagents and conditions (a) NaBr03/ Na2S204/ Et0Ac/H20 (b) (i) Tf20, pyridine, CH2CI2 (ii) PhC02Na, toluene, 60 °C (c) Deoxo-Fluor, toluene (d) (i) N,0-bis(trimet hylsilyl)acetamide, pyrimidine, or 6-chloropurine, TMSOTf, CH3CN (ii) NH3/ MeOH.

Azides and nitriles. Carboxylic acids are activated (to form RCOF) by Deoxo-Fluor for conversion into acyl azides on reaction with NaN3. Nitriles are formed by slight variation of conditions. Usually DAST can be used but the latter reagent is thermally less stable. ... 

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>. 

The C(14)-C(25)-skipped trienoic acid 1432 was prepared from (5)-3-hydroxy-2-methylpropionate in 12 steps and 8% overall yield (Scheme 1.367). Coupling 1432 with L-serine methyl ester yielded the (3-hydroxyamide 1433. Sequential cyclization of 1433 with Deoxo-fluor to an oxazoline (not shown) and oxidation with CBrCla/DBU then produced the desired skipped triene-oxazole fragment 1417 in 73% yield. 

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. 

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