Acyl compounds acid-base chemistry

Chapter 22 returns to carbonyl chemistry and a discussion of the acid-base properties of carbonyl compounds. The proton on the a-carbon (directly attached to the carbonyl) is slightly acidic and removal with a suitable base leads to an enolate anion. Enolate anions react as nucleophiles in aliphatic substitution, acyl addition, and acyl substitution reactions. 

The Weinreb amide syntheses in Figure 6.50 proceeding via the stable tetrahedral intermediates B and F are chemoselective SN reactions at the carboxyl carbon atom of carbon acid derivatives that are based on strategy 1 of the chemistry of carboxylic acid derivatives outlined in Figure 6.41. Strategy 2 of the chemistry of carboxylic acid derivatives in Figure 6.41 also has a counterpart in carbon acid derivatives, as is demonstrated by a chemoselective acylation of an organolithium compound with chloroformic acid methyl ester in this chapter s final example ... 

N-Unsubstituted y-sultams can be easily substituted at the nitrogen ring by alkylation, arylation or acylation. Arylation can be performed efficiently via copper promoted chemistry by using arylboronic acids. Alkylation is usually performed with halogen derivatives by using bases such as K2CO3, NaH, TEA. In some cases good results were obtained from hydroxy substituted compounds and DEAD/PPhs [59,60]. 

Hydroxy radical initiated oxidation of alkynes is important from the point of view of both atmospheric and combustion chemistry. Hatakeyama and coworkers have measured rate constants for the reaction of HO with acetylene, propyne and 2-butyne under atmospheric conditions. It has been suggested, based on product studies, that the jS-hydroxyvinyl radicals further react with molecular oxygen to form the corresponding peroxyl radicals and their subsequent reactions give carboxylic acid, a-dicarbonyl compounds and acyl radicals. 

Amides are very interesting and important molecules that have a nitrogen atom attached to an acyl carbon (see 68, 69, and 8 also see 92-94). There is a carboxylic acid component and an amine component. Therefore, it shordd be possible to combine a carboxylic acid and an amine in a chemical reaction to form an amide. This is partly correct, but because carboxylic acids are acids and amines are bases, complicating factors must be considered. Note that the important class of compounds called peptides in mammalian biology is linked together by peptide bonds. These peptide bonds are actually amide bonds from a chemical viewpoint, and understanding the chemistry of amides allows one to understand the chemistry of peptides better. 

Asymmetric synthesis of unnatural j8-amino acids derivatives based on azide chemistry is known. Enantioselective desymmetrization of mera-anhydride 293 mediated by cinchona alkaloids gives optically active monomethylester 294. This compound was converted into the acyl azide, which underwent Curtius degradation followed by alcoholysis of the intermediate isocyanate affording 8-amino acid derivative 295 in high enantiomeric excess. The authors observed that Grubbs catalyst was able to polymerize norbomene-type monomer 295 affording the corresponding polymer 296 in quantitative yield (Scheme 3.45). 

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