Oxygenation of enolate anions

The important factor here is delocalization of the negative charge on oxygen of enolate anions, as represented by the valence-bond structures 14a and 14b ... 

The ff-oxidation of carbonyl compounds may be performed by addition of molecular oxygen to enolate anions and subsequent reduction of the hydroperoxy group, e.g. with triethyl phosphite (E.J. Bailey, 1962 J.N. Gardner, 1968 A,B). If the initially formed a-hydroperoxide possesses another enolizable a-proton, dehydration to the 1,2-dione occurs spontaneously, and further oxidation to complex product mitctures is usually observed. 

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. 

Another base-catalyzed reaction is the addition of enolate anions derived from ketones to the 4 position of the pyridine nucleotides (Eq. 15-19). The adducts undergo ring closure and in the presence of oxygen are converted slowly to fluorescent materials. While forming the basis for a useful analytical method for determination of NAD+ (using 2-butanone), these reactions also have created a troublesome enzyme inhibitor from traces of acetone present in commercial NADH.132... 

T. H. Black, Recent Progress in the Control of Carbon Versus Oxygen Acylation of Enolate Anions , Org. Prep. Pmced. Int. 1988, 21, 179-217. 

Table 2. Direct Oxygenation of Enolates Generated by Anionic Oxy-Cope Rearrangement with Molecular Oxygen25...

Control of carbon versus oxygen acylation of enolate anions of heterocyclic carbonyl derivatives 890PP179. 

It has been proposed that part or all of the intrinsic barrier for deprotonation of a-carbonyl carbon is associated with the requirement for solvation of the negatively charged oxygen of the enolate anion [80]. However, the observation of small intrinsic barriers for deprotonation of oxygen acids by electronegative bases to form solvated anions [31] suggests that the requirement for a similar solvation of enolate anions should not make a large contribution to the intrinsic barrier for deprotonation of a-carbonyl carbon. 

The counterion of an enolate has a pronounced influence on competing transition states of enolate reactions. The effect is often the result of cation chelation by the carbonyl oxygen atom and one or more additional basic portions of the reactants. For example, alkylation of chiral enolates may lead to more or less diastereomerically pure products and selectivity often depends on the countercation. The importance of the countercation in controlling enolate reaction product distributions requires that the synthetic chemist has at hand stereoselective methods for the preparation of enolate anions with a wide variety of counterions. This chapter is divided into several sections. The 10 following sections describe important current methods for preparing Li, Mg, B, Al, Sn, Ti, Zr, Cu, Zn and other transition metal enolates. 

The addition of enolate anions to 1,2,4-triazines with an unsubstituted 5-position followed by oxidation with oxygen is also known, e.g. formation of I.160... 

Trialkylsilyl halides show a great propensity to react with the oxygen rather than the carbon of enolate anions. Stork showed that 0-alkylation allows enolates to be trapped as the trialkylsilyl enol ether, which is most useful for kinetic enolates in which a lithium enolate (such as the kinetic enolate derived from 2-methyl-cyclohexanone and LDA) is reacted with trimethylsilyl chloride to give an isolable intermediate, 112. jjig enolate is trapped with high efficiency, and conversion to the enolate is readily accomplished by treatment with methyllithium, which generates the kinetic enolate (113) and the volatile trimethylsilane (Me3SiH). This... 

The alkyl oxygen bond will break only if the carbon bonded to the alcoholic oxygen is tertiary, and the reaction conditions are such that the tertiary carbocation can form (acidic conditions are necessary). The reaction of enolate anion with an ester (using ethyl acetate from the problem) is ... 

We urge you to try to write a mechanism for the above process. You may find it useful to think of silyl groups as fat protons. Start off with silylating the carbonyl oxygen and proceed from there. Silyl enol ethers function as less reactive analogs of enolate anions. Thus, with titanium tetrachloride as a catalyst, silyl enol ethers undergo aldol condensations with a variety of carbonyl compounds. This is the Mukaiyama aldol condensation ... 

The fourth type of reaction with alkynes involves only cyclic bis-keto-ylides. Thus, the indanedione ylide (2) reacted with acetylenedicarboxylic ester to afford the new ylide (51), the result of an overall addition and oxygen transfer. Enolate anion attack on the triple bond, followed by oxetan ring formation and reopening, was proposed to account for the reaction, which was observed with several different ylides. 

Reaction of enolate anions with a,)8-unsaturated carbonyl species in Michael reactions gives products with oxygen atoms positioned in a 1,5 arrangement, which is distinct from the 1,3 positioning seen in aldol and Claisen reactions. 

In order to improve the stereoselectivity of the aldol process even further, metal salts of enolate anions other than those bearing lithium have been examined. For example, both magnesium and boron enolates have been prepared. Magnesium enolates are very much like lithium enolates in their stereoselectivity, while boron enolates, where there are relatively short metal-oxygen bonds, give improved selectivity. For the boron enolates, the (Z)-enolate is generally more stable than its E)-isomer, and erythro- or 5yn-products are developed. 

The resonance formulation of enolate anions clearly shows that the negative charge is shared between an oxygen and a carbon atom (Fig. 19.49). At which atom will alkylation be faster If there is little or no selectivity in the alkylation reaction, it will surely be of limited use. 

At lower temperatures (room temperature to 50 C), pentacovalent phosphorus compotinds of a splro structure, 35a and 35b were obtained in fairly good yields. They were formed by the combination of cationic site (phosphorus atom) and anionic site (oxygen of enolate). 

A large proportion of Davis s work has been involved in the elucidation of the transition state employed in the transfer of the oxygen from the oxaziridine to the olefin substrate. Davis favoured the planar transition state and was at the time supported by theoretical calculations however, more recent calculations favour the spiro transition state [6]. Davis has also described the asymmetric oxidation of enolate anions by chiral oxaziridines, which led to a-hydroxyketones with enanti-oselectivities of up to 95% ee [56, 57], Silyl enol ethers have also been reported to give epoxides when treated with oxaziridines, but the instability of these compounds is too great to allow isolation [37,58,59], To date, only Davis has reported successful isolation of a-silyloxy epoxides [60],... 

Protonation of this anion can occur either at the a carbon or at oxygen Protonation of the a carbon simply returns the anion to the starting aldehyde or ketone Protonation of oxygen as shown m step 2 of Figure 18 3 produces the enol... 

Reversible electron addition to the enone forms the radical anion. Rate determining protonation of the radical anion occurs on oxygen to afford an allylic free radical [Eq. (4b) which undergoes rapid reduction to an allylic carbanion [Eq. (4c)]. Rapid protonation of this ion is followed by proton removal from the oxygen of the neutral enol to afford the enolate ion [Eq. (4c)]. 

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