Acid fluorides amide synthesis

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. ... 

After insertion of CO, the resulting metal acyl complex could undergo a reductive elimination of RCOX. Alternatively, it may react with a variety of nucleophilic counterparts, which is what makes this chemistry so valuable in organic synthesis. Depending on the reaction media and the conditions, it is possible to synthesize acids, esters, amides, or acid fluorides from the same starting material, as shown in Scheme 2 for aryl-X compounds [16]. 

A -acylation with Fmoc-protected amino acid fluorides, the adducts are amenable to peptide synthesis. The heterocycle is readily cleaved to generate 3,3,3-trifluoro-2-ketopropyl amides, the members of which are potent inhibitors of esterases and proteases. 

Tris(trifluoromethyl)benzoyl fluoride was prepared in 78% yield by fluorination of benzene-1,2,3,5-tetracarboxylic acid with SF4. RfC(0)F served as a useful starting material in the synthesis of 2,4,6-tris(trifluoromethyl)-aniline, RfNHz, which is not accessible by more conventional routes. The preparation of RfNHz involves conversion of the acid fluoride to the amide and subsequent Hoffmann conversion to the amine (overall yield 56%) (25,30). The chemistry of RfNHz is largely... 

The enantiomeric synthesis of rranj-3,4-disubstituted tetrahydrothiophenes using a sulfur ylide cycloaddition has been reported <990L1667>. The sulfur ylide derived from the action of cesium fluoride on sulfide 111 underwent an asymmetric cycloaddition with chiral a,p-unsaturated camphorsultam amide 112 giving tetrahydrothiophene 113 (80% de). The configuration was confirmed by cleavage of the chiral auxiliary followed by reductive desulfurization with Raney-Ni which gave known carboxylic acid 114. 

A novel method for the convenient synthesis of alkenyl fluorides 15, as well as diflu-oromethyl-substituted alcohols 16 and amides 17, via electrophilic fluorination with one equivalent of F-Teda BF4 (6) of alkenyl boronic acids and trifluoroborates, has been reported.87 The alkenyl fluorides 15 are obtained as Z/E mixtures when the reaction is carried out with one equivalent of F-Teda BF4 in acetonitrile at room temperature. When the reaction is performed with two equivalents of F-Teda BF4 in water or a nitrile solvent the difluoromethyl-substituted alcohols 16 or amides 17, respectively, are obtained. 

A convenient synthesis of difluoroacetic acid (21) is found in first converting the amide 19 to the difluoro derivative 20 by potassium fluoride in ethylene glycol at 180,JC followed by hydrolysis.53... 

Potassium fluoride can be used to introduce fluorine in the a-position of A-substituted amides via substitution of tosyloxy groups. 2-Fluoro-A-phenylacetamide (mp 76 C) and 2-fluoro-A-phenylpropanamide (mp 62 C) are prepared by heating the corresponding tosyloxy derivatives with potassium fluoride in ethylene glycol at 100 C in 54 and 63% yield, respectively. This method is especially advantageous for the synthesis of higher a-fluoro acid derivatives, because in these cases the products cannot be distilled off from the reaction mixtures and side reactions of simple ester groups with the solvent become more important. 

Protection of glutamine and aspan ine. The 2,4-dimethoxybenzyl group (Dmb) has been recommended for protection of the amide groups of asparagine and glutamine residues in peptide synthesis. The derivatives are nicely crystalline, and the Dmb group can be removed by trifluoroacetic acid or anhydrous hydrogen fluoride. 

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