Oxygen esters, enolization

When this reaction sequence is applied to enol esters or enol ethers, the result is a-oxygenation of the starting carbonyl compound. Enol acetates form epoxides that rearrange to a-acetoxyketones. 

Although ketones are essentially inert to molecular oxygen, enolates are susceptible to oxidation. The combination of oxygen and a strong base has found some utility in the introduction of an oxygen function at carbanionic sites.200 Hydroperoxides are the initial products of such oxidations, but when DMSO or some other substance capable of reducing the hydroperoxide is present, the corresponding alcohol is isolated. A procedure that has met with considerable success involves oxidation in the presence of a trialkyl phosphite.201 The intermediate hydroperoxide is efficiently reduced by the phospite ester. 

A specially interesting case of the blocked carbonyl compound is the lactone or cyclic ester. Open-chain esters do not give aldol reactions they prefer a different reaction that is the subject of the next chapter. But lactones are in some ways quite like ketones and give unsaturated carbonyl products under basic catalysis. Enolization is unambiguous because the ester oxygen atom blocks enolization on one side. 

Oxygenation of cycloalkanones. FeCl, and a number of other Fe(lll) salts catalyze the O2 oxidation of cycloalkanones in an alcohol to lo-oxo esters. The yield is only moderate with unsubstituted ketones, but is considerably improved by an adjacent alkyl group. Trifluoromethyl or methoxy groups inhibit oxygenation. Enol acetates are easily oxidized, but lactones are merely hydrolyzed.-... 

As for preformed cationic enolate complexes, one decomposition pathway has been conclusively identified. Enolates derived from 3° alkyl esters are prone to loss of alkene to form cationic carboxylate complexes (Scheme Since donors such as THF partially impede this process, prior coordination of the ester oxygen may precede elimination. By the same token, the unhindered enolate [Me2Si(77-G5Me4)(TuN)Zr 0G(0 Bu)=CMe2 (THF)][B G6H3(GF3)2 4] decomposes at temperatures above —20°G to form the cationic carboxylate complex, even in the presence of excess... 

Carboxylic acids and esters contain far less enol than aldehydes and ketones. So little enol is present that it is difficult to measure, and the 10 values for the enolization equilibrium constants of acetic acid and methyl acetate given in Table 20.2 are only approximate. The main reason for the decreased tendency of carboxylic acids and esters to enolize appears to be the stabilization of the carbonyl group of the keto form by electron release from the alkoxy oxygen. 

Because electron release from the ester oxygen stabilizes the carbonyl to which it is attached, this enol shown in the preceding equation is more stable than a regioisomeric one in which the ester carbonyl is sacrificed and the ketone carbonyl retained. 

A regioselective aldol condensation described by Biichi succeeds for sterical reasons (G. Biichi, 1968). If one treats the diaidehyde given below with acid, both possible enols are probably formed in a reversible reaaion. Only compound A, however, is found as a product, since in B the interaction between the enol and ester groups which are in the same plane hinders the cyclization. BOchi used acid catalysis instead of the usual base catalysis. This is often advisable, when sterical hindrance may be important. It works, because the addition of a proton or a Lewis acid to a carbonyl oxygen acidifies the neighbouring CH-bonds. 

The alkylation reactions of enolate anions of both ketones and esters have been extensively utilized in synthesis. Both very stable enolates, such as those derived from (i-ketoesters, / -diketones, and malonate esters, as well as less stable enolates of monofunctional ketones, esters, nitriles, etc., are reactive. Many aspects of the relationships between reactivity, stereochemistry, and mechanism have been clarified. A starting point for the discussion of these reactions is the structure of the enolates. Because of the delocalized nature of enolates, an electrophile can attack either at oxygen or at carbon. 

The acylation of enamino ketones can take place on oxygen or on carbon. While reaction at nitrogen is a possibility, the N-acylated products are themselves acylating agents, and further reaction normally takes place. The first reported acylation of enamino ketones (72) was that of 129, prepared by acylation of the enamine (113), which was shown to have undergone O acylation because on mild hydrolysis the enol ester (130) could be isolated. A similar reaction took place with other aliphatic acid chlorides (80) and with dibasic acid chlorides [e.g., with succinyl chloride to give 118 above]. 

Therefore, transesterification reactions frequently fail when R is tertiary, since this type of substrate most often reacts by alkyl-oxygen cleavage. In such cases, the reaction is of the Williamson type with OCOR as the leaving group (see 10-14). With enol esters, the free alcohol is the enol of a ketone, so such esters easily... 

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