Acyl fluorides carboxylic acids

Acyl fluorides. Carboxylic acids are readily transformed into acid fluorides by this reagent in the presence of i-Pr2NEt. Weinreb amides can be prepared henceforth. W-Protected chiral a-amino acids are derivatized without racemization. 

During electrochemical fluorination retention of important functional groups or atoms in molecules is essential. Acyl fluorides and chlorides, but not carboxylic acids and anhydrides (which decarboxylate), survive perfluorination to the perfluorinated acid fluorides, albeit with some cyclization in longer chain (>C4) species [73]. Electrochemical fluorination of acetyl fluoride produces perfluoro-acetyl fluoride in 36-45% yields [85]. Electrochemical fluorination of octanoyl chloride results in perfluorinated cyclic ethers as well as perfluorinated octanoyl fluonde. Cyclization decreases as initial substrate concentration increases and has been linked to hydrogen-bonded onium polycations [73]. Cyclization is a common phenomenon involving longer (>C4) and branched chains. a-Alkyl-substituted carboxylic acid chlorides, fluorides, and methyl esters produce both the perfluorinated cyclic five- and six-membered ring ethers as well as the perfluorinated acid... 

Carboxylic acids react both with fluoroaminosulfiiranes such as DAST and with sulfur tetrafluonde. Whereas DAST converts the acids to acyl fluorides only, sulfur tetrafluonde further fluorinates the primarily formed acyl fluorides and ultimately converts the carboxyl group to a trifluoromethyl group. 

Theperfluoroorganozmc compounds have limited application in organic syn thesis because of their lack of reactivity However, heptafluoro I methylethylzinc iodide reacts with acyl fluorides or anhydrides of carboxylic acids in the presence of pyndine to give the corresponding ketones [7S] (equations 28 and 29) In the presence of zinc fluoride, acyl chlorides can be used as substrates [7d]... 

These reactions are most important for the preparation of acyl fluorides. " Acyl chlorides and anhydrides can be converted to acyl fluorides by treatment with polyhydrogen fluoride-pyridine solution" or with liquid HF at — 10°C. Formyl fluoride, which is a stable compound, was prepared by the latter procedure from the mixed anhydride of formic and acetic acids. Acyl fluorides can also be obtained by reaction of acyl chlorides with KF in acetic acid or with DAST. Carboxylic esters and anhydrides can be converted to acyl halides other than fluorides by the inorganic acid halides mentioned in 10-77, as well as with PhsPXa (X = Cl or but this is seldom done. Halide exchange can be carried out in a... 

Sodium or potassium phenoxide can be carboxylated regioselectively in the para position in high yield by treatment with sodium or potassium carbonate and carbon monoxide. Carbon-14 labeling showed that it is the carbonate carbon that appears in the p-hydroxybenzoic acid product. The CO is converted to sodium or potassium formate. Carbon monoxide has also been used to carboxylate aromatic rings with palladium compoimds as catalysts. In addition, a palladium-catalyzed reaction has been used directly to prepare acyl fluorides ArH —> ArCOF. ... 

Many aldehydes and ketones have been converted to g m-difluoro compounds with sulfur tetrafluoride (SF4), " including quinones, which give 1,1,4,4-tetra-fluorocyclohexadiene derivatives. With ketones, yields can be raised and the reaction temperature lowered, by the addition of anhydrous HF. Carboxylic acids, acyl chlorides, and amides react with SF4 to give 1,1,1-trifluorides. In these cases the first product is the acyl fluoride, which then undergoes the ge i-difluorination reaction ... 

Recently, acylsilanes have been utilized as useful intermediates in organic synthesis [57], For example, treatment of acylsilanes with the fluoride ion generates the corresponding acyl anions which react with electrophiles. On the other hand, by using the electrochemical method, acylsilanes serve as acyl cation equivalents because nucleophiles are introduced at the carbonyl carbon. Chemical oxidation of acylsilanes with hydrogen peroxide which affords the corresponding carboxylic acids has been reported [58], However, the anodic oxidation provides a versatile method for the introduction of various nucleophiles... 

Owing to steric hindrance, the acylation reaction must be carried out using a large excess (4-10 Eq.) of the activated acid and for an extended period. In some cases, repeat acylation is recommended. Acylation has also been successfully carried out using Fmoc-amino acid fluorides (e.g., Fmoc-Phe-F4, 4Eq. in the presence of DIEA, 1.1 Eq. 18h >98% acylation efficiency). While acylation with unhindered activated carboxylic acids are achieved in >98%, acylation with hindered carboxylic acids generally resulted in ca. 80% efficiencies. 

The reaction of sulfur tetrafluoride with carboxylic acids (aliphatic, aromatic, and heterocyclic) is of particular importance as the most general and simplest route to trifluorotnethyl derivatives. The reaction proceeds in two steps, the first step gives acyl or aroyl fluorides 1, and then catalysis in the second step by hydrogen fluoride released in the first step results in the tri-fluoromethyl derivatives 2.41... 

As mentioned above, thiazolidine-4-carboxylic acid is characterized by an anomalously low basicity and thus difficult acylation in peptide synthesis. 189 Therefore, the incorporation of this amino acid residue into a growing peptide chain is preferentially preformed via dipeptide derivatives. 139 Suitably N-protected amino acids are coupled directly to the thiazolidine-4-carboxylic acid by the acid fluoride 139 or iV-carboxyan hydride 1392111 methods. The resulting dipeptides are used as building blocks without risk of racemization 139 and standard coupling procedures are applied as pentachlorophenyl esters prepared by the mixed anhydride procedure 121 or PyBOP. 171 ... 

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