2-Butanone enolates

Electrostatic potential map for 2-butanone enolate shows most negatively-charged regions (in red) and less negatively-charged regions (in blue). 

This difference was assigned to the lesser ionicity of the OLi bond when compared to the OK one. The solvent is likely to play an important role in the equilibrium as well polar solvents seem to favor the more substituted enolate. In addition, House and Trost highlighted the fact that lithium enolates equilibrate very slowly unless a substantial excess of the free ketone is present in the solution64. Note that ab initio calculations on the naked enolates (no associated cation) of 2-butanone (Scheme 9 with R1 = H and R2 = Me) suggest that the primary and Z(O) secondary isomers are almost isoenergetic,65 while the E O) secondary analog is less stable by more than 4 kcalmol-1. Repeating these calculations for the 3-methyl-2-butanone enolates showed that the primary isomer is more stable by 4.3 kcalmol-1. 

Tine force field was then used to predict the results for fhe addition of the E and Z isomers c Ihe enol boronate of butanone (R = Me) to ethanol (R = Me). The relevant transitio. Iructures are shown in Figure 11.34. A Boltzmann distribution, calculated at the ten perature of the reaction (—78°C), predicted that the Z isomer would show almost complel syn selectivity syn anti = 99 1) and that the E isomer would be selective for the an product anti syn = 86 14). These results were in good agreement with the experunenti... 

Write the structures of the enol forms of 2 butanone that react with chlorine to give 1 chloro 2 butanone and 3 chloro 2 butanone... 

The most recent, and probably most elegant, process for the asymmetric synthesis of (+)-estrone appHes a tandem Claisen rearrangement and intramolecular ene-reaction (Eig. 23). StereochemicaHy pure (185) is synthesized from (2R)-l,2-0-isopropyhdene-3-butanone in an overall yield of 86% in four chemical steps. Heating a toluene solution of (185), enol ether (187), and 2,6-dimethylphenol to 180°C in a sealed tube for 60 h produces (190) in 76% yield after purification. Ozonolysis of (190) followed by base-catalyzed epimerization of the C8a-hydrogen to a C8P-hydrogen (again similar to conversion of (175) to (176)) produces (184) in 46% yield from (190). Aldehyde (184) was converted to 9,11-dehydroestrone methyl ether (177) as discussed above. The overall yield of 9,11-dehydroestrone methyl ether (177) was 17% in five steps from 6-methoxy-l-tetralone (186) and (185) (201). 

The idea of kinetic versus thermodynamic control can be illustrated by discussing briefly the case of formation of enolate anions from unsymmetrical ketones. This is a very important matter for synthesis and will be discussed more fully in Chapter 1 of Part B. Most ketones, highly symmetric ones being the exception, can give rise to more than one enolate. Many studies have shown tiiat the ratio among the possible enolates that are formed depends on the reaction conditions. This can be illustrated for the case of 3-methyl-2-butanone. If the base chosen is a strong, sterically hindered one and the solvent is aptotic, the major enolate formed is 3. If a protic solvent is used or if a weaker base (one comparable in basicity to the ketone enolate) is used, the dominant enolate is 2. Enolate 3 is the kinetic enolate whereas 2 is the thermodynamically favored enolate. 

Write the structures of the enol forms of 2-butanone that react... 

The initial reaction between a ketene and an enamine is apparently a 1,2 cycloaddition to form an aminocyclobutanone adduct (58) (68-76a). This reaction probably occurs by way of an ionic zwitterion intermediate (75). The thermal stability of this adduct depends upon the nature of substituents Rj, R2, R3, and R. The enolic forms of 58 can exist only if Rj and/or R4 are hydrogens. If the enamine involved in the reaction is an aldehydic enamine with no 3 hydrogens and the ketene involved is di-substituted (i.e., R, R2, R3, and R4 are not hydrogens), then the cyclo-butanone adduct is thermally stable. For example, the reaction of dimethyl-ketene (61) with N,N-dimethylaminoisobutene (10) in isopropyl acetate... 

Compare electrostatic potential maps of enolates derived from 2-butanone, 4,4-dimethyl-2-pentanone, 4,4,4-trifluoro-2-butanone and l-phenyl-2-propanone with those of acetone. Which substituents cause significant changes in the electronic structure of these enolates and what are the nature of these changes Justify your answers by making drawings of any important resonance contributors. 

In contrast, highly stereoselective aldol reactions are feasible when the boron etiolates of the mandelic acid derived ketones (/ )- and (5,)-l- t,r -butyldimethylsiloxy-l-cyclohexyl-2-butanone react with aldehydes33. When these ketones are treated with dialkylboryl triflate, there is exclusive formation of the (Z)-enolates. Subsequent addition to aldehydes leads to the formation of the iyn-adducts whose ratio is 100 1 in optimized cases. 

Surprisingly, the size of the silyl protecting group significantly influences the stereochemical outcome of aldol additions performed with the lithium enolates of (S )-l-trimethylsiloxy-and (S)-l-f< rt-butyldimethylsiloxy-l-cyclohexyl-2-butanone. Thus, the former reagent attacks benzaldehyde preferably from the Si-face (9 1), which is the opposite topicity to that found in the addition of the corresponding titanium enolates of either ketone ... 

The chlorotitanium enolate, generated by treatment of (S )-l-tm-butyldimethylsiloxy-l-cyclohexyl-2-butanone with titanium(iv) chloride and diisopropylethylamine, provides the syn-product upon reaction with benzaldehyde. The diastereoselectivity of 99 1 is defined as the ratio of the major isomer to the sum of all other isomers47bc. 

Pinacolone (3,3-dimethyl-2-butanone) adds to aldehydes in an enantioselective manner when advantage of the induction by a C 2-symmetric boron enolate derived by addition of (2/ ,5/ )-l-chloro-2,5-diphenylborolane is taken. In this way, /i-hydroxy ketones, whose absolute configuration is unknown, arc obtained with 32- 84% cc58. 

The equilibrium ratios of enolates for several ketone-enolate systems are also shown in Scheme 1.1. Equilibrium among the various enolates of a ketone can be established by the presence of an excess of ketone, which permits reversible proton transfer. Equilibration is also favored by the presence of dissociating additives such as HMPA. The composition of the equilibrium enolate mixture is usually more closely balanced than for kinetically controlled conditions. In general, the more highly substituted enolate is the preferred isomer, but if the alkyl groups are sufficiently branched as to interfere with solvation, there can be exceptions. This factor, along with CH3/CH3 steric repulsion, presumably accounts for the stability of the less-substituted enolate from 3-methyl-2-butanone (Entry 3). 

Scheme 2.11 shows some examples of Robinson annulation reactions. Entries 1 and 2 show annulation reactions of relatively acidic dicarbonyl compounds. Entry 3 is an example of use of 4-(trimethylammonio)-2-butanone as a precursor of methyl vinyl ketone. This compound generates methyl vinyl ketone in situ by (3-eliminalion. The original conditions developed for the Robinson annulation reaction are such that the ketone enolate composition is under thermodynamic control. This usually results in the formation of product from the more stable enolate, as in Entry 3. The C(l) enolate is preferred because of the conjugation with the aromatic ring. For monosubstituted cyclohexanones, the cyclization usually occurs at the more-substituted position in hydroxylic solvents. The alternative regiochemistry can be achieved by using an enamine. Entry 4 is an example. As discussed in Section 1.9, the less-substituted enamine is favored, so addition occurs at the less-substituted position. 

The comparison between the cycloaddition behavior of simple diazoketones and of ethyl diazopyruvate 56 towards the same olefin underlines the crucial influence of the ethoxycarbonyl group attached to the carbonyl function. This becomes once again evident when COOEt is replaced by an acetal function, such as in l-diazo-3,3-di-methoxy-2-butanone 86 with enol ethers and acetates, cyclopropanes rather than dihydrofurans are now obtained 113). ... 

Ketones are resistant to oxidation by dioxygen in aqueous solutions at T= 300-350 K. Transition metal ions and complexes catalyze their oxidation under mild conditions. The detailed kinetic study of butanone-2 oxidation catalyzed by ferric, cupric, and manganese complexes proved the important role of ketone enolization and one-electron transfer reactions with metal ions in the catalytic oxidation of ketones [190-194],... 

The oxidation of butanone-2, catalyzed by complexes of pyridine with cupric salts, appeared to be similar in its main features [191]. Butanone-2 catalytically oxidizes to acetic acid and acetaldehyde. The reaction proceeds through the enolization of ketone. Pyridine catalyzes the enolization of ketone. Enole is oxidized by complexes of Cu(II) with pyridine. The complexes Cu(II).Py with n = 2,3 are the most reactive. Similar results were provided by the study of butanone-2 catalytic oxidation with o-phenanthroline complexes, where Fe(III) and Mn(II) were used as catalysts [192-194],... 

Titanium enolates.1 This Fischer carbene converts epoxides into titanium enolates. In the case of cyclohexene oxide, the product is a titanium enolate of cyclohexanone. But the enolates formed by reaction with 1,2-epoxybutane (equation I) or 2,3-epoxy butane differ from those formed from 2-butanone (Equation II). Apparently the reaction with epoxides does not involve rearrangement to the ketone but complexation of the epoxide oxygen to the metal and transfer of hydrogen from the substrate to the methylene group. 

The EAN of iron in this complex is 34, but it may be a solvated ion. Treatment of the salt with water gives 2-butanone, which was presumed to have been formed via nucleophilic attack on the cation to give a TT-allyl alcohol complex. This complex was then assumed to rearrange via the tricarbonyl hydride to an enol complex, which collapses to the ketone ... 

The diacylation of isopropenyl acetate with anhydrides of dicarboxylic acids is applicable for the synthesis of several other cyclic jS-triketones in moderate yield. - It has been used for the synthesis of 2-acetylcyclohexane-l,3-dione (40% yield), 2-acetyl-4-methylcyclopentane-l,3-dione (10% yield), 2-acetyl-4,4-dimethylcyclopentane-l,3-dione (10% yield), 2-acetyl-5,5-dimethylcyclohexane-l,3-dione (10% yield), 2-acetylcyclo-heptane-l,3-dione (12% yield) and 2-acetylindane-l,3-dione (26% yield). Maleic anhydrides under more drastic conditions give acetylcyclopent-4-ene-l,3-diones in yields from 5% to 12%. The corresponding acylation of the enol acetate of 2-butanone with succinic anhydride has been used to prepare 2-methylcyclopentane-l,3-dione, an important intermediate in steroid synthesis. - ... 

The norbornene derivative 16, obtained exclusively as the exo adduct via a Diels-Alder reaction of itaconic anhydride with cyclopentadiene followed by hydrolysis and esterification [7], was found to be a suitable precursor for an enolate of type 14 (Scheme 2). Due to the quaternary center at C-3 eno-lization with base proceeded unambiguously, giving rise to a diastereomeric mixture of lactones 17/18 after reaction with hexanal. Retro-Diels-Alder reaction led to the monocyclic lactones 19/20 (2 1), elegantly unmasking the cxo-methylene group found in so many paraconic acids [8]. Hydrolysis of this mixture in refluxing butanone with 6 N HCl [9] effected epimerization... 

The importance of this approach to 33 lies in the fact that enolization of l-phenyl-2-butanone does not give pure 33 under kinetic or thermodynamic conditions. Moreover, if the acylsilane possesses a stereogenic center in the a-position, the addition occurs according to the Felkin-Anh mode. ... 

Ketone enolate 51 could also serve as a two-carbon component in [3 + 2] annulation when reacted with -heteroatom-substituted a,/ -unsaturated acylsilane 52345 Ppj. tjjg enolate of 3-methyl-2-butanone 51 (R = /-Pr) reacts with... 

For example, in one pathway H-atom elimination reactions generate the enol intermediate, which eventually rearranges to 2-butanone. In a second competing reaction pathway, H-atom addition results in direct hydrogenation to the saturated alcohol 2-butanol. 

From the base-catalyzed degradation of D-fructose (pH 8.0), Shaw and coworkers147 identified 18 compounds, none of which was (a) isomeric with the starting material, or (b) a simple dehydration product. Among the products, the hydroxy-2-butanones and 1-hydroxy-2-propanone (acetol) were shown to participate in forming the carbo-cyclic products identified, but the mechanism of their formation was not elucidated. Several furan derivatives were isolated, but no lactic acid was isolated. In a similar study but with weak acid,41 most of the products were formed by a combination of enolization and dehydration steps, with little fragmentation. 

Problem 17.5 (a) Show the tautomers of each of the following compounds, which are written as the more stable form (1) CH,CHO, (2) C.HjCOCHj, (3) CHjNO, (4) Me.C NOH, and (5) CH,CH=NCHj. (b) Which two enols are in equilibrium with (i) 2-butanone, and (ii) l-phenyl-2-butanone Which is more stable ... 

Mechanism. Addition of HgS04 generates a cyclic mercurinium ion, which is attacked by a nucleophilic water molecule on the more substituted carbon. Oxygen loses a proton to form a mercuric enol, which under work-up produces enol (vinyl alcohol). The enol is rapidly converted to 2- butanone. 

An efficient general synthesis of a variety of 3(2i/)-furanones has been developed. Aldol condensation of aldehydes with the enolate derived from 3-methyl-3-(trimethylsiloxy)-2-butanone (183) followed by Collins oxidation afforded 1,3-diketones (184). Acid catalyzed cyclodehydration leads to the corresponding 3(2//)-furanones (185) (Scheme 43)... 

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