Acid fluorides synthesis

Fluorinated and Ghlorfluorinated Sulfonic Acids. The synthesis of chlorinated and fluorinated sulfonic acids has been extensively reviewed (91,92). The Hterature discusses the reaction of dialkyl sulfides and disulfides, sulfoxides and sulfones, alkanesulfonyl haHdes, alkanesulfonic acids and alkanethiols with oxygen, hydrogen chloride, hydrogen fluoride, and oxygen—chloride—hydrogen fluoride mixtures over metal haHde catalysts, such as... 

The acid fluoride TTF-COF has been introduced as an important intermediate for synthesis of substituted TTFs <99TL8611> and the preparation and properties of salts 54 have been described . The hexaTTF system 55 has been prepared and its X-ray structure and electrochemistry examined <00CC331> and the photochromic TTF derivative 56 has been reported <99CL1071>. 

The synthesis of 3-aryltetrahydroisoquinolines was accomplished by electrophilic aromatic substitution of polysubstituted phenols and phenyl ethers with Lewis acid-generated tosyliminium ions of 2-tosyl-3-methoxytetrahydroisoquinoline derivatives <00SL801>. In addition isoquinoline was reported to react with N-tosylated (R)- or (S)-amino acid fluorides to afford optically active dihydroimidazoisoquinolinones. The reaction proceeds via acylation followed by attack of the tosylamino group at Cl of the intermediate 2-tosylaminoacylisoquinolinium salt <00TL5479>. 

J-N Bertho, A Loffet, C Pinel, F Reuther, G Sennyey. Amino acid fluorides their preparation and use in peptide synthesis. Tetrahedron Lett 32, 1303, 1991. 

LA Carpino, EME Mansour, D Sadat-Aalaee. lerl-WutoxycarbonyI and benzyloxy-carbonyl amino acid fluorides. New, stable rapid-acting acylating agents for peptide synthesis. J Org Chem 56, 2611, 1991. 

C Kaduk, H Wenschuh, M Beyermann, K Fomer, LA Carpino, M Bienert. Synthesis of Fmoc-amino acid fluorides via DAST, an alternative fluorinating agent. Lett Pept Sci 2, 285, 1995. 

A complex reaction between perfluoro 2-methylpent-2-ene and carboxylic acids in the presence of potassium carbonate and Aliquat produces the acid fluoride, as the major product, with variable amounts of the 3-acyloxy perfluorinated alkene [37]. The procedure has little value for the synthesis of either compound. 

Group-transfer polymerizations make use of a silicon-mediated Michael addition reaction. They allow the synthesis of isolatable, well-characterized living polymers whose reactive end groups can be converted into other functional groups. It allows the polymerization of alpha, beta-unsaturated esters, ketones, amides, or nitriles through the use of silyl ketenes in the presence of suitable nucleophilic catalysts such as soluble Lewis acids, fluorides, cyanides, azides, and bifluorides, HF. ... 

Table 1 summarises the list of ferrisllicate zeolites that have been prepared to-date by direct synthesis in basic media. Ferrisllicate pentasll zeolites have also been synthesised hydrothermally in an acidic, fluoride-containing medium [18,19]. Such samples, however, sometimes,... 

Much research has been done on the synthesis of perhalogenated P-sultones. The sulfonation of acyclic fluorovinyl ethers leads to a product that is stable up to slightly above room temperature. Thermolysis decomposes the ring structure under SO2 evolution and formation of acid fluorides and perfluorocyclopropane (Eq. 78). )S-Sultones have been synthesized by addition of sulfonyl chlorides to perhalogenated ketones in the presence of triethylamine. The formation of the l-oxa-2-thiacyclobutane 2,2-dioxides appears to require an activated but sterically unhindered carbonyl group because acetone, chloroacetone, trifluoroacetophenone, and p-nitroaceto-phenone did not yield the desired products. ... 

In the synthesis of fluorinated alcohols porous aluminum trifluoride has been found to be an efficient substitute for anhydrous hydrogen fluoride in combination with alkali metal acid fluorides for ring-opening reactions of aliphatic 7-oxabicyclo[4.1.0]heptane fluorohydrins under sonification.47... 

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 ... 

Standard solid-phase peptide synthesis requires the first (C-terminal) amino acid to be esterified with a polymeric alcohol. Partial racemization can occur during the esterification of N-protected amino acids with Wang resin or hydroxymethyl polystyrene [200,201]. /V-Fmoc amino acids are particularly problematic because the bases required to catalyze the acylation of alcohols can also lead to deprotection. A comparative study of various esterification methods for the attachment of Fmoc amino acids to Wang resin [202] showed that the highest loadings with minimal racemization can be achieved under Mitsunobu conditions or by activation with 2,6-dichloroben-zoyl chloride (Experimental Procedure 13.5). iV-Fmoc amino acid fluorides in the presence of DMAP also proved suitable for the racemization-free esterification of Wang resin (Entry 1, Table 13.13). The most extensive racemization was observed when DMF or THF was used as solvent, whereas little or no racemization occurred in toluene or DCM [203]. 

Due to the suppression of racemization and the ability to couple sterically hindered substrates, this methodology has been utilized in solid-phase peptide synthesis. In particular, 9-fluorenyl-methoxycarbonyl-protected amino acid fluorides have been used with this protocol.110 1,3... 

A particularly important process for the synthesis of fluorinated monomers is attack of functionalized perfluoroalkoxides onto hexafluoropropylene oxide [271, 272, 273, 274] (equation 60) or other fluorinated epoxides [275, 276], resulting in ring-opening ol the epoxide and formation of a new perfluoroalkoxide or acid fluoride... 

Wenschuh H, Beyennann M, Haber H, Seydel JK, Krause E, Bienert M, Carpino LA, El-Fahan A, Albericio F, Stepwise automated solid phase synthesis of naturally occurring peptaibols using FMOC amino acid fluorides, J. Org. Chem., 60 405-410, 1995. 

The direct conversion of the acid fluoride into the alkyl iodide by reaction with lithium iodide was also successfully applied to the synthesis of nitrogen-containing pcrfluoroalkyl iodides (Table 3). -... 

A general ketone synthesis has been developed involving reaction of trimethyl(perfluorooc-tyl)silane with acid fluorides. Yields, e.g. of 23 and 24, are generally good, and conversion of these ketones into tertiary alcohol derivatives tends to be slow, in part due to rather low solubility of the long-chain ketones.47 Indeed, it is somewhat surprising that these ketones do not react readily with trialkyl(perfluoroalkyl)silanes under these conditions to give tertiary alcohol derivatives.47... 

Alternatively, acid fluorides are used to activate the acid. Acyl fluorides are less sensitive to moisture and are more reactive toward primary and secondary amines than the corresponding acyl chloride. Furthermore, they are compatible with basic- (Fmoc and Cbz) or even acid- (Boc) labile amine protecting groups and less prone to promote racemization than their chlorinated homologs (26). Thus, the acid fluoride method is often used in peptide synthesis (27). Cyanuric fluoride 9 (28), TFFH (29), DAST (30), and deoxofluor (31) are used commonly as fluori-nating reagents (see Fig. 4). 

Olah GA, Nojima M, Kerekes I. Synthetic methods and reactions IV. 1 Huorination of carboxylic acids with cyanuric fluoride. Synthesis 1973 8 487. 

M. Lerner, R. Hagiwara and N. Bartlett, Synthesis of Main-Group Graphite Fluoroanion Salts with Chlorine-Assisted Oxidation by Lewis-Acid Fluorides, J. Fluorine Chem. 57 (1992) 1-13. 

---