Conversion of an Enol to a Ketone

Step 1 In aqueous acid, the first step is proton transfer to the carbon-carbon double bond. 

Step 2 The conjugate acid of the ketone transfers a proton from oxygen to a water molecule, yielding a ketone. 

The aldehyde or ketone is called the keto form, and the keto enol equilibration is referred to as keto-enol isomerism or keto-enol tautomerism. Tautomers are constitutional isomers that equilibrate by migration of an atom or group, and their equilibration is called tautomerism. Keto-enol isomerism involves the sequence of proton transfers shown in Mechanism 9.2. 

The first step, protonation of the double bond of the enol, is analogous to the protonation of the double bond of an alkene. It takes place more readily, however, because the carbocation formed in this step is stabilized by resonance involving delocalization of a lone pair of oxygen. 

Of the two resonance forms A and B, B has only six electrons around its positively charged carbon. A satisfies the octet rule for both carbon and oxygen. It is more stable than B and more stable than a carbocation formed by protonation of a typical alkene. 

Give the structure of the enol formed by hydration of 2-butyne, and write a series of equations showing its conversion to its corresponding ketone isomer. 

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FIGURE 9 6 Conversion of an enol to a ketone takes place by way of two solvent mediated proton transfers A proton is transferred to carbon in the first step then removed from oxygen in the second... 

FIGURE 9.6 Conversion of an enol to a ketone takes place by way of two solvent-mediated proton transfers. 

The initial product of this reaction has a double bond (en) and an OH group ( /) and is therefore called an enol. But the enol cannot be isolated because it is rapidly converted into a ketone. The conversion of an enol into a ketone will appear again in many subsequent chapters and therefore warrants further discussion. Acid-catalyzed conversion of an enol to a ketone occurs via two steps (Mechanism 10.2). 

The mechaiusm for the conversion of an enol to a ketone under acidic conditions is shown next. In Section 7.8, we will see that the reaction can also be catalyzed by bases. 

Although the conversion of an aldehyde or a ketone to its enol tautomer is not generally a preparative procedure, the reactions do have their preparative aspects. If a full mole of base per mole of ketone is used, the enolate ion (10) is formed and can be isolated (see, e.g., 10-105). When enol ethers or esters are hydrolyzed, the enols initially formed immediately tautomerize to the aldehydes or ketones. In addition, the overall processes (forward plus reverse reactions) are often used for equilibration purposes. When an optically active compound in which the chirality is due to an asymmetric carbon a to a carbonyl group (as in 11) is treated with acid or base, racemization results. If there is another asymmetric center in the molecule. 

The process of converting an enol to a ketone. Pyruvate kinase catalyzes a ketonization reaction in the conversion of the enolpyruvate intermediate to pyruvate. See... 

It is very hard (close to impossible) to prevent the equilibrium from being established. Imagine that you are performing a reaction that generates an enol as the product, and you take great efforts to remove all traces of add or base. Your hope is that you can prevent the equilibrium from being established, so as to avoid the conversion of the enol into a ketone. But you will find that your efforts will likely be unsuccessfiil. Even trace amounts of acid or base adsorbed on the glassware (that you caimot remove) will allow the equiUbrium to be established. 

The second type of reaction which is commonly associated with carbonyl compounds involves the generation of a nucleophilic enol or enolate ion. Although the conversion of a ketone to the tautomeric enol does not necessarily involve any other species, the generation of an enolate requires a base (Fig. 3-4). In this latter reaction, the putative nucleophile may act as a general base. 

Lead tetraacetate was employed by Stoodley and coworkers for an oxidative isomerization in their synthesis of 4-demethoxydaunomycinone (47). The diene (48) reacted with the oxirane dienophile (49) via the least hindered endo transition state to give the cycloadduct (50) in 86% yield. Hydrolysis of the silyl enol ether followed by reduction of the oxirane and introduction of the acetylene moiety gave the compound (51), which was oxidatively isomerized with LTA in acetic acid to give the quinone (52). All that remained now to complete the synthesis was conversion of the acetylene to a methyl ketone and dealkylation of the ether, llie last two steps were accomplished in an over l yield of 38%, the low yield attributable to problems in formation of the hydroxy group from the ether (Scheme 11). Bulman-Page and Ley employed LTA for a similar transformation in their synthesis of demethoxydaunomycinone and related anthracyclinones. 

Michael addition of metal enolates to a,/3-unsaturated carbonyls has been intensively studied in recent years and provides an established method in organic synthesis for the preparation of a wide range of 1,5-dicarbonyl compounds (128) under neutral and mild conditions . Metal enolates derived from ketones or esters typically act as Michael donors, and a,-unsaturated carbonyls including enoates, enones and unsaturated amides are used as Michael acceptors. However, reaction between a ketone enolate (125) and an a,/3-unsaturated ester (126) to form an ester enolate (127, equation 37) is not the thermodynamically preferred one, because ester enolates are generally more labile than ketone enolates. Thus, this transformation does not proceed well under thermal or catalytic conditions more than equimolar amounts of additives (mainly Lewis acids, such as TiCU) are generally required to enable satisfactory conversion, as shown in Table 8. Various groups have developed synthons as unsaturated ester equivalents (ortho esters , thioesters ) and /3-lithiated enamines as ketone enolate equivalents to afford a conjugate addition with acceptable yields. 

One keto-enol tautomerism forms an enediol a second then forms the ketone carbonyl group in fructose 6-phosphate. (See Section 12.8A and Problems 12.34 and 12.35.) The conversion of the aldose to a ketose is necessary to facilitate the chemistry in Reaction 4. 

A mixture of an acid anhydride and a ketone is saturated with boron trifluoride this is followed by treatment with aqueous sodium acetate. The quantity of boron trifluoride absorbed usually amounts to 100 mol per cent, (based on total mola of ketone and anhydride). Catalytic amounts of the reagent do not give satisfactory results. This is in line with the observation that the p diketone is produced in the reaction mixture as the boron difluoride complex, some of which have been isolated. A reasonable mechanism of the reaction postulates the conversion of the anhydride into a carbonium ion, such as (I) the ketone into an enol type of complex, such as (II) followed by condensation of (I) and (II) to yield the boron difluoride complex of the p diketone (III) ... 

This enzymic conversion involves two enzymes, a dehydrogenase and an isomerase. The dehydrogenase component oxidizes the hydroxyl group on pregnenolone to a ketone, and requires the oxidizing agent cofactor NAD+ (see Box 11.2). The isomerase then carries out two tautomerism reactions, enolization to a dienol followed by production of the more stable conjugated ketone. 

The conversion of an a, -unsaturated aldehyde or ketone into an allylic acetal or ketal, followed by SN2 -type attack of a nucleophile, leads, after hydrolysis of an initially formed enol ether, to a fi-sub-stituted carbonyl compound. The overall sequence (Scheme 23) is equivalent to a direct conjugate addition, but has the advantage that it allows the temporary introduction of a chiral auxiliary group if a chiral (C2-symmetric) diol is used in the acetalization step, die subsequent nucleophilic addition leads to a mix-... 

In the presence of an electrophile, tautomerization of a substrate with a C=0 double bond to its enol only takes place when catalyzed by either a Bronsted- or a Lewis acid. The proton-catalyzed mechanism is shown for the ketone — enol conversion B — iso-B (Figure 12.4), the carboxylic acid —> enol conversion A — E (Figure 12.6), the carboxylic acid bromide — enol conversion E —> G (Figure 12.7) and the carboxylic acid ester — enol conversion diethyl-malonate —> E (Figure 12.9). Each of these enol formations is a two-step process consisting of the protonation to a carboxonium ion and the latter s deprotonation. The mechanism of a Lewis acid-catalyzed enolization is illustrated in Figure 12.5, exemplified by the ketone —> enol conversion A —> iso-A. Again, a protonation to a carboxonium ion and the latter s deprotonation are involved the Lewis acid-complexed ketone acts as a proton source (see below). 

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