Ketones, enolate anions hydroxylation

Thus the reactions of cyclic or acyclic enamines with acrylic esters or acrylonitrile can be directed to the exclusive formation of monoalkylated ketones (3,294-301). The corresponding enolate anion alkylations lead preferentially to di- or higher-alkylation products. However, by proper choice of reaction conditions, enamines can also be used for the preferential formation of higher alkylation products, if these are desired. Such reactions are valuable in the a substitution of aldehydes, which undergo self-condensation in base-catalyzed reactions (117,118). Monoalkylation products are favored in nonhydroxylic solvents such as benzene or dioxane, whereas dialkylation products can be obtained in hydroxylic solvents such as methanol. The difference in products can be ascribed to the differing fates of an initially formed zwitterionic intermediate. Collapse to a cyclobutane takes place in a nonprotonic solvent, whereas protonation on the newly introduced substitutent and deprotonation of the imonium salt, in alcohol, leads to a new enamine available for further substitution. 

Only Cram (36) has published a rationale for the very high (99%) enantiomeric excess achieved in the reaction of methyl vinyl ketone and the hydrindanone in the presence of the chiral crown ether. This mechanism envisions a bimolecular complex comprising the potassium cation and chiral host as one entity and the enolate anion of the hydrindanone as the counterion. Methyl vinyl ketone lies outside this complex. The quinine-catalyzed reaction appears to have a termo-lecular character, since the hydroxyl of the alkaloid probably hydrogen bonds with the methyl vinyl ketone—enhancing its acceptor properties—while the quin-uclidine nitrogen functions as the base forming the hydrindanone—alkaloid ion pair. 

Intermediate enols can also be oxidized by indirect electrosynthesis (vide supra) halide anions are used as oxidation mediators. A multistep reaction converts ketones into a-hydroxylated acetals when oxidized electrochemically in the presence of iodine as the redox catalyst (Scheme 48) [196],... 

The idea of kinetic versus thermodynamic control can be illustrated by discussing briefly the formation of enolate anions from unsymmetrical ketones. A more complete discussion of this topic is given in Chapter 7 and in Part B, Chapter 1. Any ketone with more than one type of a-proton can give rise to at least two enolates when a proton is abstracted. Many studies, particularly those of House,have shown that the ratio of the two possible enolates depends on the reaction conditions. If the base is very strong, such as the triphenylmethyl anion, and there are no hydroxylic solvents present, enolate 6 is the major product. When equilibrium is established between 5 and 6 by making enolate formation reversible by using a hydroxylic solvent, however, the dominant enolate is 5. Thus, 6 is the product of kinetic control... 

The new carbon-carbon bond-forming reactions presented in this chapter offer many new opportunities to synthesize molecules. Three examples are presented to illustrate some of these transformations. In the first example, 138 is synthesized from alkene 139. Disconnection of 138 takes advantage of the five-carbon unit of 139 between the carbonyl unit and the hydroxyl unit. This disconnection is chosen because it leads to two fragments, and the ketone fragment is chosen as the donor because it is equivalent to an enolate anion, derived from 3-methyl-2-butanone. 

In order to activate the 21 position to halogenation, it is hrst converted to an oxalate. Condensation of the triketone with ethyl oxalate in the presence of alkoxide proceeds preferentially at the 21 position to give (12-2) due to the well-known enhanced reactivity of methyl ketones. Reaction of the crude sodium enolate with bromine leads to the dibromide (12-3), the oxalate moiety being cleaved under the reaction conditions. The Favorskii rearrangement is then used to, in effect, oxidize the 17 position so as to provide a site for the future hydroxyl group. Thus, treatment of (12-3) with an excess of sodium methoxide hrst provides an anion at the 17 position (12-4). This then cyclizes to the transient cyclopropanone (12-5)... 

Enolate hydroxylation is a problem of long standing. Direct oxygenation succeeds with the fully substituted enolates of certain a,a-disubstituted ketones and a variety of carboxylic acid derivatives (ester anions, acid dianions, amide anions), but the reaction of enolates, RCH = C(0 )R or CH2 = C(0 )R, with oxygen results in complex products of overoxidation. The stable... 

The methine proton in the keto form and the hydroxyl proton in the enol form of jS-diketones are acidic and their removal generates 1,3-diketonate anions (2), which are the source of an extremely broad class of coordination compounds referred to generically as diketonates or acetylacetonates. The synthesis, structure and properties of these compounds form the focus of this chapter. Di-ketonate anions are powerful chelating species and form complexes with virtually every transition and main group element. The scope of this chemistry is very large and it has been assessed earlier in several excellent reviews.9-14... 

Aldehydes may be prepared from the lower homolog or a ketone or ester by reaction with the anion of formaldehyde mono- or dithioacetal. The j6-hydroxythioacetal may be reduced with elimination of a hydroxyl group and phenylthiolate. The resulting enol ether or thioenol ether can be transformed into an aldehyde on acid hydrolysis or reaction with mercuric chloride [82],... 

Oxidations - 3,5-Dinitroperbenzoic acid is a stable storable peracid equivalent in activity to trlfluoroperacetic acid. A full paper has appeared which gives the experimental details for the a-hydroxylation of carbonyl compounds by treatment of the anions of enol silanes with Mo05 HMPA (MOOPH). Anions from carboxylic esters (LiN(iPr)2>LDA -78°C) can be efficiently, regiospecifically chlorinated or brominated by treatment with respectively CCl or CBr. Treatment of enol silanes from conjugated ketones with m-chloroperbenzolc acid (MCPBA) followed by removal of silicon affords the a-hydroxyketones. ... 

Under acidic conditions, this is followed by decarboxylation, giving an enol intermediate, which then tautomerises to the ketone product. Addition of the hydroxyl group of trifluoroperacetic acid to the ketone gives a tetrahedral intermediate. Donation of the electrons in the H-0 bond, 1,2-migration of one of the alkyl groups and loss of the carboxylate anion then gives the product lactone. 

An important general reaction of enolate ions involves nucleophilic addition to the electrophilic carbonyl carbon atom of the aldehyde or ketone from which the enolate is derived. A dimeric anion 18 results, which may then be neutralized by abstraction of a proton to produce a p-hydroxycarbonyl compound, 19 (Eq. 18.10). If the reaction is performed in hydroxylic solvents such as water or an alcohol, the source of the proton may be the solvent, whose deprotonation will regenerate the base required for forming the enolate ion. Thus, the overall process is catalytic in the base that is used. 

The addition of borane to alkenes is stereospecifically cis and leads to the formation of tri-alkylboranes. These may be oxidized to alcohols using the anion of hydrogen peroxide. Overall addition of water is achieved, in a c/s-stereospecific, anti-Markovnikov manner. Hydroboration/oxidation of alkynes gives ketones, after tautomerization of the enol formed. c/s-Dihydroxylation of alkenes is accomplished with catalytic OSO4 plus an oxidant such as NMO or K3[Fe(CN)g]. This contrasts with the formation of frans-diols by epoxidation of alkenes followed by the opening of the epoxide with hydroxyl ion. 

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