Recent Advances in the Synthesis of Acyl Fluorides

Abstract

Acyl fluorides are valuable intermediates in organic synthesis. They are increasingly employed in peptide synthesis, in challenging esterification and amidation reactions or in transition-metal-catalyzed transformations. This review summarizes recent advances in their preparation.1 Introduction2 Nucleophilic Fluorination2.1 α-Fluoroamine Reagents2.2 Sulfur-Based Reagents2.3 Metal Catalysts2.4 Phosphorus-Based Reagents2.5 N,N′-Dicyclohexylcarbodiimide/HF·Pyridine2.6 Uranium Hexafluoride2.7 Bromine Trifluoride3 Radical Fluorination4 Conclusion

Rapid Access to Fluorinated Anilides via DAST-Mediated Deoxyfluorination of Arylhydroxylamines

“…On the basis of previous reports and the above mechanistic findings, a postulated reaction mechanism is proposed in Scheme . Nucleophilic substitution of a fluorine in DAST by 1 gives intermediate IA along with the elimination of HF.…”

“…Generally, direct fluorination can be achieved through (1) transition-metal-catalyzed direct C–H fluorination, (2) deoxyfluorination, (3) oxidative fluorination with fluoride, or (4) nucleophilic fluorination of aryl electrophiles . In this regard, a large number of commercially available fluorination reagents, such as xenon difluoride, N -fluorobis­(phenyl)­sulfonimide (NFSI), Selectfluor, diethylaminosulfur trifluoride (DAST), NMe 4 F, AgF, and AgF 2 have been developed to achieve direct fluorination in a selective and efficient manner…”

Carboxylic Acid Deoxyfluorination and One-Pot Amide Bond Formation Using Pentafluoropyridine (PFP)

“…A cyl fluorides have emerged as a highly valuable class of molecules in the field of synthetic organic chemistry, and they can be applied in a wide variety of useful transformations. 1 Acyl fluorides have been used as key reagents in challenging amidations/esterifications and coupling reactions, 2 as a source of anhydrous fluoride ions, 3 and more recently in nickelcatalyzed decarbonylative borylations. 4 Despite the clear interest within the synthetic community to utilize acyl fluorides, access to this class of molecule may require the use of toxic reagents, harsh reaction conditions, or the application of approaches that have limited substrate tolerance in some cases.…”

Gram-Scale Preparation of Acyl Fluorides and Their Reactions with Hindered Nucleophiles

“…1 Although studied for more than a century, 2 they have recently found numerous applications in the synthesis of peptides, 1a esters, 3 amides, 4 acylphosphonates, 5 and as valuable substrates for transition-metal-catalyzed transformations. 1` c d , 6 Early methods for their preparation 7 were based mainly on the halogen exchange of acyl halides using inorganic salts such as KHF 2 , 8 spray-dried KF, 9 KF/TEBA, 10 NaF, 11 or CaF 2 -KF, 12 which had many limitations including the need for tedious drying, prolonged reaction times at high temperatures, and isolation of products by fractional distillation. 13 In turn methods developed in last few years utilize more sophisticated reagents designed for direct conversion of carboxylic acids under mild conditions.…”

“…13 In turn methods developed in last few years utilize more sophisticated reagents designed for direct conversion of carboxylic acids under mild conditions. 14 15 16 17 18 19 20 However, the latter approach usually suffers from high cost of the reagents, low atom economy, and the formation of significant amounts of waste, and thus is only suitable for transformations of more valuable substrates. At the same time, convenient synthesis of simple alkanoyl and aroyl fluorides on a multigram scale remains rather lacking.…”