Room Temperature Deoxyfluorination of Benzaldehydes and α-Ketoesters with Sulfuryl Fluoride and Tetramethylammonium Fluoride

Abstract

A method for the room temperature deoxyfluorination of benzaldehydes and α-ketoesters using sulfuryl fluoride and Me 4 NF is described. A large scope of aryl and heteroaryl substrates is demonstrated, and this method compares favorably to other common deoxyfluorination methods for many substrates.

One‐Pot Substitution of Aliphatic Alcohols Mediated by Sulfuryl Fluoride

“…Sulfuryl fluoride (SO 2 F 2 )h as been used as ac ommodity chemicalf or over 50 years, but it has only recently received significant attention as ar eagent for organic synthesis. [8] Despite the recent surge of interest, there are only af ew reports on the use of SO 2 F 2 to activate aliphatic alcohols. [9] The most significant problem with aliphatic alcohol activation is that the correspondingf luorosulfate intermediate (Scheme2, 7)i s highlyr eactive and is prone to undesired side reactions, such as fluoride substitution (9), [10] elimination (10), [9a] or substitution with solvent (11).…”

Sulfonyl Fluorides and Their Analogs Deoxofluorination

“…A seminal work on deoxofluorination of carbonyl compounds with SO 2 F 2 has also been reported by Sanford et al [17]. The room temperature deoxofluorination of a large scope of (hetero) aromatic aldehydes and (hetero)aryl a-ketoesters using SO 2 F 2 in the presence of Me 4 NF afforded the corresponding difluoromethyl-and a-gemdifluoroester-substituted (hetero)arene products in high yields (Scheme 5) [17].…”

Deoxyfluorination of (Hetero)aryl Aldehydes Using Tetramethylammonium Fluoride and Perfluorobutanesulfonyl Fluoride or Trifluoromethanesulfonic Anhydride

“…An attractive route to access these functional groups is the deoxyfluorination of (hetero)aryl aldehydes . Our group recently reported the deoxyfluorination of (hetero)aryl aldehydes to afford the corresponding difluoromethyl (hetero)arenes using a combination of anhydrous tetramethylammonium fluoride (NMe 4 F) and sulfuryl fluoride (SO 2 F 2 ) (Figure A) . Since SO 2 F 2 is an inexpensive commodity chemical, this deoxyfluorination method has great potential for application on process scale.…”

“…Since SO 2 F 2 is an inexpensive commodity chemical, this deoxyfluorination method has great potential for application on process scale. However, the laboratory scale use of SO 2 F 2 can be hampered by safety concerns associated with using this toxic gas . In an effort to make this chemistry more accessible on a laboratory scale, we sought to identify an alternative method that employs NMe 4 F in conjunction with a liquid sulfur(VI) electrophile to convert aryl aldehydes to difluoromethyl (hetero)arenes .…”

“…Our studies on the deoxyfluorination of (hetero)aryl aldehydes with NMe 4 F/SO 2 F 2 showed that N,N ‐dimethylformamide (DMF) was the optimal solvent . As such, we initially examined the reaction of 4‐bromobenzaldehyde with 2 equiv.…”