Carboxyl-O-cleavage

The hydrolysis of carboxylic esters can in principle take place either as carboxyl-O cleavage, i.e., as an SN reaction at the carboxyl carbon—... 

For carboxylic esters, the rate ratios were much smaller, although still in the same order, so that this reaction is closer to a pure E mechanism, although the transition state stiU has some carbocationic character. Other evidence for a greater initial C-O cleavage with carboxylic esters is that a series of 1-arylethyl acetates followed rather than a, showing carbocationic character at the 1 position. ... 

Fig. 2. Schematic diagram of the catalytic mechanism of 20S proteasomes. A proton transfer from the hydroxyl group of Thrl of /3 subunits to its own terminal amino group initiates the nucleophilic attack (I). As a result of the nucleophilic addition to the carbonyl carbon of the scissile peptide bond, a tetrahedral intermediate is formed (II). By an N—O acyl rearrangement, an ester is formed (the acyl enzyme) and the amino-terminal cleavage product is released (III). Finally, hydrolysis of the acyl enzyme yields the carboxyl-terminal cleavage product and frees the enzyme for another reaction cycle (IV).

In addition to a multiple-turnover mechanism, inversion of stereochemistry may also result from the intermediacy of a phosphorylated enzyme carboxyl group (Scheme 3a).Breakdown via C—O bond cleavage results in overall stereochemical inversion. Hydrolysis of acetyl phosphate, catalysed by divalent metal ions, proceeds by predominant C—O cleavage (7.4 < pH < 8.2) (Klinman and Samuel, 1971). 

Deprotection of the silyl esters 291 yielded the nitrones 292 resulting from a carboxylate assisted cleavage of the oxaziridine C-O bond (Scheme 86) [157]. 

Unsubstituted 3-alkyl- or 3-aryl-isoxazoles undergo ring cleavage reactions under more vigorous conditions. In these substrates the deprotonation of the H-5 proton is concurrent with fission of the N—O and C(3)—-C(4) bonds, giving a nitrile and an ethynolate anion. The latter is usually hydrolyzed on work-up to a carboxylic acid, but can be trapped at low temperature. As shown by Scheme 33, such reactions could provide useful syntheses of ketenes and /3-lactones (79LA219). 

Photolytic cleavage reactions (e.g., of o-nitrobenzyl, phenacyl, nitrophenylsul-fenyl derivatives) take place in high yield on irradiation of the protected compound for a few hours at 254-350 nm. For example, the o-nitrobenzyl group, used to protect alcohols, amines, and carboxylic acids,has been removed by irradiation. Protective groups that have been removed by photolysis are described at the appropriate places in this book in addition, the reader may wish to consult five review articles. 

The latter is an exttemely reactive species. Trifluoroacetate is a good leaving group and facilitates cleavage of the O—Br bond. The acyl hypohalites are also the active halogenating species in solutions of the hypohalous acids in carboxylic acids, where they exist in equilibrium. 

Hunig and Salzwedel (20) report that the acylation of the pyrrolidine enamine of 3-methylcyclohexanone with propionylchloride followed by the hydrolysis and the base cleavage of the resulting dione isomers (71) and (72) and subsequent reduction of the keto groups gave a 3 7 mixture of the carboxylic acids (73 and 74), respectively. Vig et al. (39), however, found o o o o... 

The reaction is likely to proceed by a radical-chain mechanism, involving intermediate formation of carboxyl radicals, as in the related Kolbe electrolytic synthesis. Initially the bromine reacts with the silver carboxylate 1 to give an acyl hypobromite species 3 together with insoluble silver bromide, which precipitates from the reaction mixture. The unstable acyl hypobromite decomposes by homolytic cleavage of the O-Br bond, to give a bromo radical and the carboxyl radical 4. The latter decomposes further to carbon dioxide and the alkyl radical 5, which subsequently reacts with hypobromite 3 to yield the alkyl bromide 2 and the new carboxyl radical 4Z... 

Alkyl esters are efficiently dealkylated to trimethylsilyl esters with high concentrations of iodotrimethylsilane either in chloroform or sulfolane solutions at 25-80° or without solvent at 100-110°.Hydrolysis of the trimethylsilyl esters serves to release the carboxylic acid. Amines may be recovered from O-methyl, O-ethyl, and O-benzyl carbamates after reaction with iodotrimethylsilane in chloroform or sulfolane at 50—60° and subsequent methanolysis. The conversion of dimethyl, diethyl, and ethylene acetals and ketals to the parent aldehydes and ketones under aprotic conditions has been accomplished with this reagent. The reactions of alcohols (or the corresponding trimethylsilyl ethers) and aldehydes with iodotrimethylsilane give alkyl iodides and a-iodosilyl ethers,respectively. lodomethyl methyl ether is obtained from cleavage of dimethoxymethane with iodotrimethylsilane. 

A crystal structure of the C02 derivative of (8), K[Co(salen)( 71-C02)], haso been reported in which the Co—C bond is 1.99 A, the C—O bonds are both equivalent at 1.22 A and the O-C-O angle is 132°.125 Carboxylation of benzylic and allylic chlorides with C02 in THF-HMPA was achieved with (8) electrogenerated by controlled-potential electrolysis,126 in addition to reductive coupling of methyl pyruvate, diethyl ketomalonate and / -tolylcarbodiimide via C—C bond formation. Methyl pyruvate is transformed into diastereomeric tartrates concomitant with oxidation to the divalent Co(salen) and a free-radical mechanism is proposed involving the homolytic cleavage of the Co—C bond. However, reaction with diphenylketene (DPK) suggests an alternative pathway for the reductive coupling of C02-like compounds. 

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