Reactions via Enols and Enolates

When a solution of (/ )-(+)-2-methyl-l-phenylbutan-l-one (see the following reaction) in aqueous ethanol is treated with either acids or bases, the solution gradually loses its optical activity. After a time, isolation of the ketone shows that it has been completely racem-ized. The (-I-) form of the ketone has been converted to an equimolar mixture of its enantiomers through its enol form. 

A base catalyzes the formation of an enol through the intermediate formation of an eno-late anion. 

In acyclic ketones, the enol or enolate formed can be ( ) or (Z). Protonation on one face of the ( ) isomer and protonalion on the same fece of the (Z) isomer produces enantiomers. 

Would optically active ketones such as the following undergo acid- or base-catalyzed racan-ization Explain your answer. 

Keto-enol tautomerization can sometimes be used to convert a less stable epimer to a more stable one. This equilibration process is an example of epimerization. An example is the epimerization of cw-decalone to tran -decalone  

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In fact, even very weak bases are enough for most l, 3-dlcarbonyI compounds and piperidine and acetic acid combine to form a mild buffered system that facilitates both conjugate addition and aldol reactions via enol Intermediates. The trifluoromethyl ketone is extremely electrophilic so the aldol reaction proceeds very smoothly. 

Boron enolates generated from a-heterosubstituted thioacetates by treatment with 105 undergo highly enantioselective and diastereoselective condensations. On the other hand, chiral esters 106 and 107, and amides 108 behave differently. V-Acyl derivatives of the bicyclic isoxazolidine 109 ° readily undergo syn-selective aldol reactions via enol borates. 

Longmire, C.F., and Evans, S.A., Jr., Stereoselective aldol reactions via enolates of a-acylphosphonate diesters, J. Chem. Soc., Chem. Commun., 922, 1990. 

Among the ethers of prolinol, (5)-2-methoxymethylpyrrolidinc [SMP, (S)-10] has found most applications. It is readily prepared from prolinol by the normal sodium hydride/iodo-methane technique9,13 (sec also Section 2.3. for O-alkylations of other amino alcohols) and is also commercially available. An improved synthesis from proline avoids the isolation of intermediates and gives the product (which is highly soluble in water) by continuous extraction14. SMP has been used as the lithium salt in deprotonation and elimination reactions (Section C.) and as an auxiliary for the formation of chiral amides with carboxylic acids, which in turn can undergo carbanionic reactions (Sections D.l.3.1.4., D.l. 1.1.2.. D.l. 1.1.3.1., in the latter experimental procedures for the formation of amides can be found). Other important derivatives are the enamines of SMP which are frequently used for further alkylation reactions via enolates (Sections D.l.1.2.2.. where experimental procedures for the formation of enamines are... 

Chiral 2-oxazolidones are useful recyclable auxiliaries for carboxylic acids in highly enantioselective aldol type reactions via the boron enolates derived from N-propionyl-2-oxazolidones (D.A. Evans, 1981). Two reagents exhibiting opposite enantioselectivity ate prepared from (S)-valinol and from (lS,2R)-norephedrine by cyclization with COClj or diethyl carbonate and subsequent lithiation and acylation with propionyl chloride at — 78°C. En-olization with dibutylboryl triflate forms the (Z)-enolates (>99% Z) which react with aldehydes at low temperature. The pure (2S,3R) and (2R,3S) acids or methyl esters are isolated in a 70% yield after mild solvolysis. 

With certain other nucleophiles addition takes place at the carbon-carbon double bond rather than at the carbonyl group Such reactions proceed via enol intermediates and are described as conjugate addition ox 1 4 addition reactions... 

Study of the mechanism of this complex reduction-Hquefaction suggests that part of the mechanism involves formate production from carbonate, dehydration of the vicinal hydroxyl groups in the ceUulosic feed to carbonyl compounds via enols, reduction of the carbonyl group to an alcohol by formate and water, and regeneration of formate (46). In view of the complex nature of the reactants and products, it is likely that a complete understanding of all of the chemical reactions that occur will not be developed. However, the Hquefaction mechanism probably involves catalytic hydrogenation because carbon monoxide would be expected to form at least some hydrogen by the water-gas shift reaction. 

A commonly used alternative to the direct bromination of ketones is the halogenation of enol acetates. This can be carried out under basic conditions if necessary. Sodium acetate, pyridine or an epoxide is usually added to buffer the reaction mixture. The direction of enolization is again dependent upon considerations of thermodynamic and kinetic control therefore, the proportion of enol acetates formed can vary markedly with the reaction conditions. Furthermore, halogenation via enol acetates does not necessarily give the same products as direct halogenation of ketones 3. 23... 

In a manner analogous to classic nitrile iinines, the additions of trifluoro-methylacetonitrile phenylimine occur regiospecifically with activated terminal alkenes but less selectively with alkynes [39], The nitnle imine reacts with both dimethyl fumarate and dimethyl maleate m moderate yields to give exclusively the trans product, presumably via epimenzation of the labile H at position 4 [40] (equation 42) The nitrile imine exhibits exo selectivities in its reactions with norbornene and norbornadiene, which are similar to those seen for the nitrile oxide [37], and even greater reactivity with enolates than that of the nitnle oxide [38, 41], Reactions of trifluoroacetomtrile phenyl imine with isocyanates, isothiocyanates, and carbodiimides are also reported [42]... 

The mechanism of the Fiesselmann reaction between methylthioglycolate and a,P-acetylenic esters proceeds via consecutive base-catalyzed 1,4-conjugate addition reactions to form thioacetal Enolate formation, as a result of treatment with a stronger base, causes a Dieckmann condensation to occur providing ketone 8. Elimination of methylthioglycolate and tautomerization driven by aromaticity provides the 3-hydroxy thiophene dicarboxylate 9. 

A recent paper by Singh et al. summarized the mechanism of the pyrazole formation via the Knorr reaction between diketones and monosubstituted hydrazines. The diketone is in equilibrium with its enolate forms 28a and 28b and NMR studies have shown the carbonyl group to react faster than its enolate forms.Computational studies were done to show that the product distribution ratio depended on the rates of dehydration of the 3,5-dihydroxy pyrazolidine intermediates of the two isomeric pathways for an unsymmetrical diketone 28. The affect of the hydrazine substituent R on the dehydration of the dihydroxy intermediates 19 and 22 was studied using semi-empirical calculations. ... 

A similar trend was observed in the reaction of tri- and tetrasubstituted etiolates derived from 2-unsubstituted or 2-bromo substituted 3,4-dihydro-6-methoxy-1(2//)-naphthalenone16. The trisubstituted cnolate underwent addition to (—)-(2 )-2-(4-methylphenylsulfinyl)-2-cyclopen-tenone via attack on the nonchelated conformation to give an adduct of d.r. [(2S)/(2/ )] 77 23. The tetrasubstituted enolate underwent addition to the corresponding ( + )-(5)-enone via attack on the chelated conformation to give an adduct with the same absolute configuration at C-2 but with d.r. [(2R) (2S)] 95.5-97 4.5-3. 

C-H insertion also occurs in the reactions with acetone and acetophenone, presumably through the rearrangement of transient OH-substituted phosphi-ranes [87]. C-C insertions occur for diketones to give 45 and have been postulated to occur via initial 1,2-addition to the conjugated enol 44 [87]. Diimines 46 also undergo C-C insertions [88]. Based on a theoretical evaluation, the products 47 are considered to result from a 2,3-sigmatropic rearrangement of initial formed P,N-ylids. 

Boron enolates are often used for aldol reactions. Boron enolates are usually prepared from the corresponding carbonyl compounds, tertiary amine, and a boron source (e.g., dibutylboron triflates). The aldol reactions proceed via a six-membered transition state to give high diastereo-selectivity which depends upon the geometry of the boron enolates. 

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