Deoxofluor

Figure 2.2 Fluorination with nucleophilic reagents (e.g., DAST Deoxofluor)...

Alternatively, acid fluorides are used to activate the acid. Acyl fluorides are less sensitive to moisture and are more reactive toward primary and secondary amines than the corresponding acyl chloride. Furthermore, they are compatible with basic- (Fmoc and Cbz) or even acid- (Boc) labile amine protecting groups and less prone to promote racemization than their chlorinated homologs (26). Thus, the acid fluoride method is often used in peptide synthesis (27). Cyanuric fluoride 9 (28), TFFH (29), DAST (30), and deoxofluor (31) are used commonly as fluori-nating reagents (see Fig. 4). 

Scheme 2.57 Synthesis of diethyla-mino sulfurtrifluoride (DAST) [127], morpholino sulfurtrifluoride (MOST), and bis(methoxyethylamino) sulfurtrifluoride (BAST commercialized by Air Products, Inc. under the brand name Deoxofluor) and its analogs.

With the aim of obtaining a fluorination reagent which can be safely handled on a larger scale, other derivatives such as the morpholino sulfurtrifluoride (MOST) or the methoxyethyl analog (Deoxofluor) were developed [129]. Deoxofluor also decomposes at elevated temperatures, but it does so without a thermal run-away reaction... 

Because DAST (diethylaminosulfur trifluoride) and BAST (bis(2-methoxyethyl) aminosulfur trifluoride commercialized as Deoxofluor) hydrolyze readily, giving HF, similar precautions must be taken as for handling hydrofluoric acid and its amine complexes [4]. Because neat DAST tends to explode if heated above 40-50 °C, safety screens are recommended if DAST is heated. For reactions or more inert substrates, requiring higher temperatures, BAST (Deoxofluor) was developed as a safer alternative, because it decomposes on heating only slowly and without detonation [11]. 

Scheme A.7 Fluorination of alcohols with BAST (Deoxofluor) [11].

The new (x,a-difluoroamides 137 result from the reactions of a-ketoacid 138 with Deoxofluor or DAST. " ... 

Deoxofluor reacts with glyoxal hydrate 139 to form in good yield polyfluoroethers... 

Singh, R.P. Twamley, B. Shreeve, J.M. Polyfluoroether derivatives via nucleophihc fluorination of glyoxal hydrates with deoxofluor. J. Org. Chem. 2002, 67, 1918-1924. 

Singh, R.P. Shreeve, J.M. Concentration-dependent reactions of deoxofluor with arylglyoxal hydrates a new route to polyfluoro ethers. Org. Lett. 2001, 3, 2713-2715. 

As noted, reactions with DAST or Deoxofluor typically proceed with inversion of configuration. However, for the constrained substrate shown in Scheme 15.10, the configuration is retained due to neighbouring group participation of the amide group. ... 

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