Categories: C-F Bond Formation >
Synthesis of acyl fluorides
The use of the bench-stable, solid reagent (Me4N)SCF3 enables a convenient, highly efficient, and selective transformation of aliphatic and aromatic carboxylic acids to acyl fluorides at room temperature. This base- and additive-free method offers high functional group tolerance and facile product purification via filtration.
T. Scattolin, K. Deckers, F. Schoenebeck, Org. Lett., 2017, 19, 5740-5743.
Bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor reagent) is a new deoxofluorinating agent that is much more thermally stable than DAST (C2H5)2NSF3. It is effective for the conversion of alcohols to alkyl fluorides, aldehydes and ketones to the corresponding gem-difluorides, and carboxylic acids to the trifluoromethyl derivatives with, in some cases, superior performance compared to DAST.
G. S. Lal, G. P. Pez, R. J. Pesaresi, F. M. Prozonic, H. Cheng, J. Org. Chem., 1999, 7048-7054.
XtalFluor-E promotes a deoxofluorination reaction of carboxylic acids to provide a wide range of acyl fluorides in good yields after a simple filtration through a pad of silica gel. This transformation is assisted by a catalytic amount of NaF and occurs at room temperature in EtOAc. A sequential deoxofluorination/amidation is also possible.
M. Gonay, C. Batisse, J.-F. Paquin, J. Org. Chem., 2020, 85, 10253-102604.
Aminodifluorosulfinium tetrafluoroborate salts act as efficient deoxofluorinating reagents when promoted by an exogenous fluoride source and, in most cases, exhibited greater selectivity by providing less elimination byproduct as compared to DAST and Deoxo-Fluor. Aminodifluorosulfinium tetrafluoroborates are storage-stable, and unlike DAST and Deoxo-Fluor do not react violently with water.
F. Beaulieu, L.-P. Beauregard, G. Courchesne, M. Couturier, F. LaFlamme, A. L'Heureux, Org. Lett., 2009, 11, 5050-5053.
A fast and simple method for deoxyfluorination of carboxylic acids employs commodity chemicals (PPh3, NBS, fluoride) to afford products in excellent yields under mild conditions. The protocol offers scalability, high functional group tolerance, chemoselectivity, and easy purification of products.
S. B. Munoz, H. Dang, X. Ispizua-Rodriguez, T. Mathew, G. K. S. Prakash, Org. Lett., 2019, 21, 1659-1663.
Deoxo-Fluor is a versatile and mild reagent for acyl fluoride generation and subsequent one-flask amide coupling. The conversion of acids to amides and Weinreb amides and the use of Deoxo-Fluor as peptide-coupling reagent have been explored. Products were isolated after facile purification in good yields.
J. M. White, A. R. Tunoori, B. J. Turunen, G. I. Georg, J. Org. Chem., 2004, 69, 2573-2576.
A near-stoichiometric amount of N-Formylsaccharin, an easily accessible crystalline compound, has been employed as an efficient CO source in a mild Pd-catalyzed fluorocarbonylation of aryl halides to afford the corresponding acyl fluorides in high yields. The acyl fluorides obtained could be readily transformed into various carboxylic acid derivatives such as carboxylic acid, esters, thioesters, and amides in a one-pot procedure.
T. Ueda, H. Konishi, K. Manabe, Org. Lett., 2013, 15, 5370-5373.
Activated ketones such as α-oximinoketones can serve as starting materials for the preparation of acyl fluorides via a pull-and-push-driven fluorinative C-C bond cleavage. The use of diethylaminosulfur trifluoride (DAST) derivatives led to a highly efficient and chemoselective reaction. The method is mild, fast, and scalable.
D. Kim, H. N. Lim, Org. Lett., 2020, 22, 7465-7469.