Enolate ions hydroxylation

DMSO and /V, A- dime th y I fo nn a in i d c (DMF) are particularly effective in enhancing the reactivity of enolate ions, as Table 1.2 shows. Both of these compounds belong to the polar aprotic class of solvents. Other members of this class that are used as solvents in reactions between carbanions and alkyl halides include N-mcthyI pyrro I i donc (NMP) and hexamethylphosphoric triamide (HMPA). Polar aprotic solvents, as their name implies, are materials which have high dielectric constants but which lack hydroxyl groups or other... 

Solvation can have a large effect on intrinsic barriers or intrinsic rate constants, especially hydrogen bonding solvation of nitronate or enolate ions in hydroxylic solvents. Table 4 reports intrinsic rate constants in water and aqueous DMSO for a number of representative examples.19,20,23 25,40,54 56 Entries 1-4 which refer to nitroalkanes show large increases in ogka when... 

The mechanism of dehydration is shown below (Fig.L). First of all, the acidic proton is removed and a new enolate ion is formed. The electrons in the enolate ion can then move in such a fashion that the hydroxyl group is expelled to give the final product, i.e. an a, p-unsaturated aldehyde. In this example, it is possible to change the conditions such that one gets the Aldol reaction product or the a, P-unsaturated aldehyde, but in some cases only the a, p-unsaturated carbonyl product is obtained, particularly when extended conjugation is possible. 

The /3-hydroxy ketone must be dehydrated to give the final product. Under these basic conditions, the usual alcohol dehydration mechanism (protonation of hydroxyl, followed by loss of water) cannot occur. Removal of another proton gives an enolate ion that can lose hydroxide in a strongly exothermic step to give the final product. 

Acidities of / -Dicarbonyl Compounds Table 22-1 compares the acidities of some carbonyl compounds with the acidities of alcohols and water. Notice the large increase in acidity for compounds with two carbonyl groups beta to each other. The a protons of the jS-dicarbonyl compounds are more acidic than the hydroxyl protons of water and alcohols. This enhanced acidity results from increased stability of the enolate ion. The negative charge is delocalized over two carbonyl groups rather than just one, as shown by the resonance forms for the enolate ion of diethyl malonate (also called malonic ester). 

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. 

Amylose is thus extremely susceptible to degradation in the presence of hydroxyl ion. Two mechanisms may be involved (1) a stepwise degradation caused by the reducing end-group s undergoing enolization followed by degradation to acidic products (this must occur in the presence or absence of oxygen), and (2) a random, catalytic, hydrolytic scission of 4—>l-a-D... 

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. 

The procedure reported here provides a convenient method for the a-hydroxylation of ketones which form enolates under the reaction conditions. The reaction has been applied successfully to a series of para-substituted acetophenones, 1-phenyl-1-propanone, 3-pentanone, cyclopentanone, cyclohexanone, cycloheptanone, cyclododecanone, 2-methyl cyclohexanone, 2-norbornanone and benzalacetone. In the case of a steroidal example it was shown that a carbon-carbon double bond and a secondary hydroxyl group are not oxidized. A primary amino function, as in the case of p-aminoacetophenone, is not affected.5 Similarly, a tertiary amino ketone such as tropinone undergoes the a-hydroxy at ion reaction.5... 

The Claisen rearrangement of lactonic enolates provides a new route to cycloalkenes. Cyclocitral was converted to the lactone (642) through a multistep sequence, the lactone deprotonated with LDA in THF at -78 °C, and the enolate quenched with f-butyldimethyl-chlorosilane (80JA6889, 6891). The crude ketene acetal (643) was heated at 110 °C for 10 h, and the product treated with fluoride ion to afford a single acid. Replacement of the quaternary carboxyl group by hydroxyl was accomplished through use of the carboxy inversion reaction (Scheme 147). The product (645) of this last reaction was identical with an authentic sample of widdrol in all respects excluding its optical rotation. 

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