Cyclohexanone enolate ion

The three-step sequence of 0) enolate ion formation, (2) alkylation, and (3) hydrolvsis/decarboxylation is applicable to all /Tketo esters with acidic a hydrogens, not just to acetoacetic ester itself. For example, cyclic /3-keto esters such as ethyl 2-oxocycIohexanecarboxylate can be alkylated and decarboxy-lated to give 2-substituted cyclohexanones. 

The lithium enolates of cyclopentanone and cyclohexanone undergo addition-elimination to the 2,2-dimethylpropanoic acid ester of ( )-2-nitro-2-hepten-l-ol to give 2-(l-butyl-2-nitro-2-propenyl)cycloalkanones with modest diastereoselection. An analogous reaction of the enolate ion of cyclohexanone with the 2,2-dimethylpropanoic acid ester of (Z)-2-nitro-3-phenyl-2-propenol to give 2-(2-nitro-l-phenyl-2-propenyl)cyclohexanones was also reported. The relative configuration of these products was not however determined6. 

The same authors studied the stereochemistry of alkylation of 4-t-butyl-cyclohexanone. Alkylation of enolate ion 467 with triethyloxonium fluorobor-ate yielded a mixture of 0-alkyl product and approximately equal amounts of... 

House and Fischer (38) have found that lithium dimethyl cuprate reacts with enone 108 and yields a mixture of trans and cis 3,5-dimethyl-cyclohexanones 109 and 110 in a 98 2 ratio. Similar results were observed by Allinger and Riew (39) using methylmagnesium iodide in the presence of copper(I) chloride. In another case, Heathcock and co-workers (AO) observed the exclusive formation of the trans isomer V[2 from enone 111 no cis isomer was detected. Thus, the preferred mode of approach by cuprate reagent is also 76 + 78 which leads to a chair-like enolate ion. 

The dark reaction of pinacolone enolate ion and Phi in DMSO was described167. The same reaction is stimulated by light and inhibited by radical scavengers. This system was used to study the reactivity of different ketone enolate ions with Phi. In competition experiments, the following reactivity order was determined 2-acetylcyclohexanone (unreactive) < phenylacetone (0.39) < cyclohexanone (0.67) < pinacolone (1.00) < acetone (1.09) < 2-butanone (1.10) < 3-pentanone (1.40)168. 

To avoid the formation of two products, deprotonation of the ketone must produce a single enolate ion. Therefore, the ketone must be symmetrical, like cyclohexanone in the preceding example, or have a structure that favors the formation of the enolate ion at only one of the a-carbons, as is the case in the following example ... 

He adds sodium ethoxide to cyclohexanone (in ethanol solution) to make the enolate ion then he adds benzyl bromide to alkylate the enolate ion, and heats the solution for half an hour to drive the reaction to completion. 

Enamines are intermediate in reactivity more reactive than an enol, but less reactive than an enolate ion. Enamine reactions occur under milder conditions than enolate reactions, so they avoid many side reactions. Enamines displace halides from reactive alkyl halides, giving alkylated iminium salts. The iminium ions are unreactive toward further alkylation or acylation. The following example shows benzyl bromide reacting with the pyrrolidine enamine of cyclohexanone. 

In the gas phase, the reaction of ethyl cations, C2H , with the ambident 2,4-pentanedione (which is 92% enolized at 25 °C in the gas phase) leads predominantly (>95%) to alkylation at the hard oxygen site and not at the soft carbon atom, as predicted by the HSAB concept [662]. Accordingly, the gas-phase alkylation of the enolate ion of cyclohexanone gives only the O- and no C-alkylation product [848], and the gas-phase acylation of acetophenone enolate with trifluoroacetylchloride leads predominantly to the 0-acylation product (0/C ratio = 6.0) [849]. 

Nucleophilic attack on ( -alkene)Fp+ cations may be effected by heteroatom nucleophiles including amines, azide ion, cyanate ion (through N), alcohols, and thiols (Scheme 39). Carbon-based nucleophiles, such as the anions of active methylene compounds (malonic esters, /3-keto esters, cyanoac-etate), enamines, cyanide, cuprates, Grignard reagents, and ( l -allyl)Fe(Cp)(CO)2 complexes react similarly. In addition, several hydride sources, most notably NaBHsCN, deliver hydride ion to Fp(jj -alkene)+ complexes. Subjecting complexes of type (79) to Nal or NaBr in acetone, however, does not give nncleophilic attack, but instead results rehably in the displacement of the alkene from the iron residue. Cyclohexanone enolates or silyl enol ethers also may be added, and the iron alkyl complexes thus produced can give Robinson annulation-type products (Scheme 40). Vinyl ether-cationic Fp complexes as the electrophiles are nseful as vinyl cation equivalents. ... 

The anion Z has a finite lifetime and propagates further by stepwise addition of more monomer. However, death of the polymer enolate ion can occur by a spontaneous, thermally-induced cyclization to form a terminal,-substituted cyclohexanone ring (2) which results in termination. ... 

For example, when hydroxide ion or an alkoxide ion is used to remove an a-hydrogen from cyclohexanone, only a small amount of the carbonyl compound is converted into the enolate ion because the product acid (H2O) is a stronger acid than the reactant acid (the ketone). (Recall that the equilibrium of an acid-base reaction favors dissociation of the strong acid and formation of the weak acid see Section 2.5.)... 

An important reaction of quaternary ammonium fluoride ions is the displacement of an enolate ion from a silyl enol ether. This reaction is ordinarily conducted stoi-chiometrically. Mention of the method is also made in Chap. 10 (see Eq. 10.3). The trimethylsilyl enol ether of cyclohexanone, for example, can be prepared easily and is stable [18]. Fluoride ion associated with tetrabutylammonium cation attacks silicon forming a very stable silicon-fluorine bond and stoichiometrically liberating cyclohexanone enolate which can then be monoalkylated. Several examples of this reaction (see Eq. 9.3) are included in Table 9.1. 

In the presence electron-rich alkenes such as 2,3-dimethylbut-2-ene, irradiation of CA gives the allylethers 59 and 60, whereas with BQ, a substantial amount of the spiro-oxetane is also formed.The product distribution of the allyl ethers is rationalized by steric effects on the H+ abstraction and on the recombination of radicals as well as spin densities. The crucial role of solvent polarity in CA photochemistry is well illustrated by the results of a study into the reaction between the quinone and cyclohexanone enol trimethylsilyl ether 61 using time-resolved (ps) spectroscopy. The influence of the solvent occurs following the formation of the radical ion pair (CA - 61+-). The CA- species is short lived in nonpolar solvents and cyclohex-2-en-l-one and 62 are the reaction products, whereas in acetonitrile, the lifetime is much longer, which allows diffuse separation of the radical ion pair and transference of the TMS to the solvent. The resulting ketyl radical couples to CA - yielding 63. 

A number of studies of the acid-catalyzed mechanism of enolization have been done. The case of cyclohexanone is illustrative. The reaction is catalyzed by various carboxylic acids and substituted ammonium ions. The effectiveness of these proton donors as catalysts correlates with their pK values. When plotted according to the Bronsted catalysis law (Section 4.8), the value of the slope a is 0.74. When deuterium or tritium is introduced in the a position, there is a marked decrease in the rate of acid-catalyzed enolization h/ d 5. This kinetic isotope effect indicates that the C—H bond cleavage is part of the rate-determining step. The generally accepted mechanism for acid-catalyzed enolization pictures the rate-determining step as deprotonation of the protonated ketone ... 

These mechanistic interpretations can also be applied to the hydrogenation of cyclohexanones. In acid, the carbonium ion (19) is formed and adsorbed on the catalyst from the least hindered side. Hydride ion transfer from the catalyst gives the axial alcohol (20). " In base, the enolate anion (21) is also adsorbed from the least hindered side. Hydride ion transfer from the catalyst followed by protonation from the solution gives the equatorial alcohol (22). 

The initial addition step is reversible allowing isomerization of the ( )- and (Z)-nitroalkenes and equilibration between the initially formed syn- and ann -imminium ion adducts. The spn-ad-duct is identical to that obtained from the lithium enolate of cyclohexanone and ( >(2-nitro-cthenyl)benzenc. The preference for the. yyu-adduct can be rationalized by inferring the transition state 1 which is similar to that proposed for the reaction of (-E)-nitroalkcnes with ( )-eno-lates11, l2. 

Various enol silyl ethers and quinones lead to the vividly colored [D, A] complexes described above and the electron-transfer activation within such a donor/acceptor pair can be achieved either via photoexcitation of charge-transfer absorption band (as described in the nitration of ESE with TNM) or via selective photoirradiation of either the separate donor or acceptor.41 (The difference arising in the ion-pair dynamics from varied modes of photoactivation of donor/acceptor pairs will be discussed in detail in a later section.) Thus, actinic irradiation with /.exc > 380 nm of a solution of chloranil and the prototypical cyclohexanone ESE leads to a mixture of cyclohexenone and/or an adduct depending on the reaction conditions summarized in Scheme 5. 

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