Bis(2-methoxyethyl)aminosulfur Trifluoride (Deoxo-Fluor^®)

Originally reported by Lal and coworkers in 1999,¹ bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor^®) has shown remarkable utility in organic synthesis as a thermally stable alternative to (diethylamino)sulfur trifluoride (DAST). Deoxo-Fluor^® can easily convert alcohols to alkyl fluorides, aldehydes and ketones to gem-difluorides, and carboxylic acids to acid fluorides or trifluoromethyl derivatives (Scheme 1).²

A recent report showed the use of Deoxo-Fluor^® in the synthesis of a 2-azabicyclo[2.1.1]hexane analogue of 4-fluoroproline
(Scheme 2).³ Although the reaction generally proceeds with inversion at the chiral carbon, the configuration is retained in this constrained substrate due to neighboring-group participation of the amide group.

Deoxo-Fluor^® can be used to effect a wide array of additional transformations. One recent example highlights its use in the syntheses of a series of chiral C2 bis-oxazoline ligands (Scheme 3).⁴ The chemoselectivity of Deoxo-Fluor^® was superior to other reagents, including DAST, and was tolerant of steric and electronic variations within the ligands. Furthermore, the Deoxo-Fluor^® protocol also allowed the majority of the ligands to be purified without requiring chromatography.

Gunda Georg at the University of Kansas has reported the use of Deoxo-Fluor^® in a one-flask protocol to convert acids to amides and peptides or Weinreb amides (Scheme 4).⁵ The reaction proceeded under mild conditions and provided the desired products in high yields with facile purification.

The Kangani group has devoted several publications to one-pot transformations achievable with Deoxo-Fluor^®.⁶ Generally, the reactions begin with the conversion of a carboxylic acid to an acid fluoride, which is then reacted with various nucleophiles to produce oxazolines, aldehydes, ketones, benzoxazoles, oxadiazoles, acyl azides or nitriles (Scheme 5).