Ketones and aldehydes enolization

In Part 111 we cover that broad category of organic compounds called the carbonyls. First we give you an overview of Ccirbonyl basics, including structure, reactivity, and spectroscopy. Then we go into more detail on aldehydes and ketones, enols and enolates, and carboxylic acids and their derivatives. 

The conjugate addition of unstabilized enolates to various acceptors was conceptually recognized by early researchers however, complications were encountered depending on the enolates and acceptors employed. Reexamination of this strategy was made possible by the development of techniques for kinetic enolate formation. This discussion is divided into three enolate classes (a) aldehyde and ketone enolates, azaenolates or equivalents, (b) ester and amide enolates, dithioenolates and dienolates and (c) a,0-carboxylic dianions and a-nitrile anions, in order to emphasize the differential reactivity of various enolates with various acceptors."7 The a-nitrile anions are included because of their equivalence to the hypothetical a-carboxylic acid anion. 

OL-Iodo aldehydes and ketones. Enol silyl ethers are converted by this system into a-iodo carbonyl compounds in yields of >80%. 1 he method fails with enamines, and is only marginally useful with enol ethers. This system converts cyclohexene into trans- -chloro-2-iodocyclohexane (66% yield). 

Although carboxylic acids and their derivatives are somewhat weaker carbon acids than aldehydes and ketones, it is generally possible to quantitatively convert them to the corresponding metal enolates with dialkylamide bases, the most popular of which is LDA. - - Thus, monoanions of saturated esters, lactones, nitriles, /VA -dialkylamides and V-alkyllactams and dianions of carboxylic acids and V-unsub-stituted amides and lactams are easily prepared in aprotic solvents such as THF and C-alkylated with a variety of simple and functionalized SN2-reactive alkylating agents at room temperature or below. When more-hindered systems are involved, the basicity of the metal dialkylamide and the reactivity of the metal enolate can be enhanced by the addition of HMPA. Of course, many of the indirect methods used for the generation of aldehyde and ketone enolates are also applicable to the preparation of enolates of carboxylic acid derivatives (Section 1.1.2.1). O-Alkylations or dialkylations at carbon generally are of minimal importance with metal enolates of carboxylic acid derivatives. 

Compared with other synthetic intermediates, enolates show a decreased reactivity. The differences in reactivity are most striking in reactions with alkylating agents [1] and epoxides [6]. The reactivities of the various types of enolates towards alkyl halides decrease in the order C=C(0 )NR2 (amide-enolate) C=C(0 )0R (ester enolate) C=CO (ketone-enolate). Metallated nitriles, imines, and S,S-acetals are, in general, much better nucleophiles than enolates in alkylations and ft-hydroxyalkylations [1], Furthermore, the alkylation of aldehyde and ketone enolates usually does not stop after the mono-functionalization [12]. The decreased reactivity of (especially) aldehyde and ketone enolates also appears in thiolations with disulfides [2]. A solution of lithiated cyclohexanone in THF does not react at 20°C with CH3SSCH3 [1,2]. 

By reorganizing certain related topics, the number of chapters in Organic Chemistry has been reduced from 29 in the 7th edition to 27 in the 8th. Thus, nucleophilic aromatic substitution has now joined electrophilic aromatic substitution in Chapter 12 Reactions of Arenes Electrophilic and Nucleophilic Aromatic Substitution while Chapter 20 Enols and Enolates combines the treatment of ester enolates with that of aldehyde and ketone enols and enolates. 

ALDEHYDE AND KETONE ENOLATES WITH AUXILIARY-CONTAINING ELECTROPHILES 61... 

Enamines are the synthetic equivalents of aldehyde and ketone enolates. 

Acidity of Aldehydes and Ketones Enolate Ions CHAPTER 18... 

Conversely, the reverse approach, that is, the addition of aldehyde and ketone enolates to nitroolefins, gave better results using short peptides than proline. 

In contrast with carboxyl-derived enolates, few general, highly stereoselective methods for the asymmetric alkylation of aldehyde and ketone enolates are available [15, 20]. Some of the key problems associated with these are widely appreciated. The aldehyde and ketone counterparts are more weakly nucleophilic than carboxamide-derived enolates. In addition, the ease with which the products undergo epimerization under relatively mild acidic or alkaline conditions can provide a practical limit to the isolation of pure adducts. 

---