Enolates, Enols and Enamines

Electrostatic potential map for enamine shows negatively-charged regions (in red) and positively-charged regions (in blue). 

HOMO of silyl enol ether reveals most nucleophilic sites. 

Ketones and aldehydes ean be eonverted into a number of nucleophilie moleeules with similar reaetivity patterns. 

Examine the eleetrostatic potential map of eaeh nueleophile (enamine, silyl enol ether, lithium enolate and enol) with emphasis on the face of the nucleophilic alkene carbon. Rank the nucleophiles from most electron rich to least electron rich. What factors are responsible for this order (Hint For each molecule, consider an alternative Lewis structure to that given above that places a negative charge on the nucleophilic carbon.) 

Some electrophile-nucleophile reactions are guided more by orbital interactions than by electrostatics. The key interaction involves the donor orbital on the nucleophile, i.e., the highest-occupied molecular orbital (HOMO). Examine the HOMO of enamine, silyl enol ether, lithium enolate and enol. Which atom is most nucleophilic, i.e., which site would produce the best orbital overlap with an electrophile  

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Alkylation of Enols, Enolates, and Enamines with spr C-L Acylation of Ends, Enolates, and Enamines with 0=C-L Sinks Amides and Amidates... 

Scheme 7.2 Enols, enolates, and enamines for enantioselective protonations.

Carbon nucleophiles play a central role in organic chemistry, as they form the basis of carbon-carbon bond formation. A few are shown in Figure 1.2, including such carbanionic species as organolithiums (RLi), Grignard reagents (typically written as RMgBr), and the cyanide (CN ) and acetylide (R-C=C ) anions. Other examples such as enolates, enols, and enamines will be briefly discussed in Section 1.15. 

In addition to preparation of arylhydrazones from the carbonyl compounds and an arylhydrazine, the Japp-Klingemann reaction of arenediazonium ions with enolates and enamines is an important method for preparation of arylhydrazones. This method provides a route to monoarylhydrazones of a-dicarbonyl compounds from /3-keto acids and to the hydrazones of pyruvate esters from / -keto esters. Enamines also give rise to monoarylhydrazones of a-diketones. Indolization of these arylhydrazones provides the expected 2-acyI-or 2-alkoxycarbonyl-indoles (equations 95-97). 

Enzymologists have freely proposed enolate anions, enols, and enamines as intermediates for many years. Such intermediates have been demonstrated for some nonenzymatic acid- or base-catalyzed reactions, but how can enzymes form enolates at pH 7 without the use of strong acids or bases The microscopic pRa value of an a-hydrogen in a ketone or aldehyde is about 17-20.72 98"... 

A few other reactions were omitted because they did not fit into the current presentation (nitrile and alkyne chemistry, cyanohydrin formation, reductive amination, Mannich reaction, enol and enamine reactions). 

Arylation is possible by the addition of triplet aryl cations to neutral nucleophiles such as alkenes, alkynes, enols, and enamines (photo SN1 mechanism). For alkenes, the... 

It is of great interest to compare this last value with the keto-enol equilibrium constant obtained similarly for acetone = 0.35 x 10-8). Indeed, in many enzyme-catalysed reactions, aldolisation for example, enamine formation is not rate-limiting, and the rate is usually controlled by subsequent electrophilic additions. Consequently, the rate depends on enamine reactivity and on the enamine concentration at equilibrium. Therefore, if one wants to compare the two processes, via enol and via enamine, in order to explain why the enamine route is usually preferred, the difference in equilibrium constants for enol and enamine formation must be taken into account. Data on ketone to enol and ketone to enamine equilibrium constants show that the enamine and enol concentrations are of similar magnitude even for relatively small concentrations of primary amine. Thereafter, since the enamine is much more reactive than the enol for reactions with electrophilic reagents (in a ratio of 4-6 powers of ten for proton addition), it can be easily understood why the amine-catalysed pathway is energetically more favourable. 

Gilbert stark was bom in Brussels and became an assistant professor of chemistry at Harvard In 1948. Since 1953, Stork has been at Columbia University In New York. Sfnce the 1950s, he has pioneered new synthetic methods, among them many involving. enolates and enamines. 

A useful assortment of carbon-carbon bond forming reactions such as alkylation of enolates and enamines and carbon-oxygen bond forming reactions such as epoxidation with ylides have been described in this chapter. 

The enamine reaction provides an alternative method for selective alkylation and acylation of aldehydes and ketones. The enamine group is both a protecting group for carbonyl compounds and a directing or activating group for further elaboration. Note the relationship between enolates and enamines ... 

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