Carboxylic esters, base cleavage

The smooth conversion of the enol acetate (151) into an A -acyl derivative (152) under extremely mild conditions points to the high acylating capacity of these esters. This cleavage of isoxazolium salts is also caused by other anions of carboxylic acids, and thus they can be readily converted to reactive enol esters. A very convenient and specific synthesis of peptides due to Woodward et is based on... 

When P-keto esters are treated with concentrated base, cleavage occurs, but is on the keto side of the CR2 group (arrow) in contrast to the acid cleavage mentioned on page 810. The products are a carboxylic ester and the salt of an acid. However, the... 

Our final example is a base-labile 4-(phenylsulfonyl)methyl-l,3-dioxolane protecting group for aldehydes and ketones.4 Protection is carried out by the reaction of diol 17,1 (obtained by dihydroxylation of ally phenyl sulfone) with a carbonyl compound in the presence of pyridinium p-toluene sulfonate [Scheme 2.17], Cleavage is accomplished by treatment with DBU. /erf-Butyldimethylsilyl ethers, p-toluenesulfonate esters, tetrahydropyranyl ethers, carboxylic esters and benzoates are well tolerated. A disadvantage to the use of 17.1 is the introduc-... 

When p-keto esters are treated with concentrated base, cleavage occurs, but is on the keto side of the CR2 group (arrow) in contrast to the acid cleavage mentioned on page 838. The products are a carboxylic ester and the salt of an acid. However, the utility of the reaction is somewhat hmited by the fact that decarboxylation is a side reaction, even under basic conditions. p-Diketones behave similarly to give a ketone and the salt of a carboxylic acid. With both p-keto esters and p-chketones, OEt can be used instead of OH, in which case the ethyl esters of the corresponding acids are obtained instead of the salts. In the case of p-keto esters, this is the reverse of Claisen condensation (16-85). The similar cleavage of cychc a-cyano... 

Catalytic reduction of the nitro-epoxide (8.1, R = COOMe) leads directly to the indole carboxylic ester but when R = H, reduction of the nitro-epoxide does not give the indole. However, cleavage of the epoxide and reduction of the nitro group gives the amine (8.2) which is cyclized by a strong base. 

Before discussmg the mechanism of cleavage of carboxylic acid esters and amides by hydrolases, some chemical principles are worth recalling. The chemical hydrolysis of carboxylic acid derivatives can be catalyzed by acid or base, and, in both cases, the mechanisms involve addition-elimination via a tetrahedral intermediate. A general scheme of ester and amide hydrolysis is presented in Fig. 3. / the chemical mechanisms of ester hydrolysis will be... 

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