Base-Catalyzed Keto-Tautomerism

Under basic conditions, the proton is first removed from its old position in the enol, and then replaced in its new position on the adjacent carbon atom of the ketone or aldehyde. 

To move a proton (as in a tautomerism) under basic conditions, try removing the proton from its old position, then adding it to the new position. 

Hydroboration of 1-hexyne, for example, gives the vinylborane with boron on the less highly substituted carbon. Oxidation of this intermediate gives an enol that quickly tautomerizes to hexanal. 

The hydroboration-oxidation of internal alkynes produces ketones. 

For each compound, give the product(s) expected from (I) HgS04/H2S04-catalyzed hydration and (2) hydroboration-oxidation. 

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Figure 25.8 Fructose, a ketose, is a reducing sugar because it undergoes two base-catalyzed keto-enol tautomerizations that result in conversion to an aldose.

Show how enols and enolate ions act as nucleophiles. Give mechanisms for acid-catalyzed and base-catalyzed keto-enol tautomerisms. 

D presentation of the chromatogram of 5-(+)-naproxen dissolved and stored in the acidic medium (development in the second direction). In this figure, we can see the single 3D peak of 5-(+)-naproxen only. In that way, we provided sufficient experimental evidence in favor of the base-catalyzed keto-enol tautomerism as a driving force for the configuration change of the chirally pure 5-(+)-naproxen. 

Problem 17.3 Compare the mechanisms for (a) base-catalyzed and (b) acid-catalyzed keto-enol tautomerism. 

Pyridine is an important cofactor in the reaction system that leads to cleaner reactions and better yields of products than in its absence.15 It can act either as a u-donor for Pb(rv) or as a base catalyzing the keto-enol tautomerism. The u-donor effect was evidenced spectroscopically by the formation of adducts of pyridine with lead tetraacetate.45,4511 Moreover, pyridine catalyzed the ligand redistribution of twcfc-methoxyphenyllead triacetate to bis( r/ -mcthoxy-phenyl)lead diacetate. Other u-donor catalysts can be used and their nature is highly important for the success of the reaction. NaOMe and HOBT showed a modest effect, but a thousand-fold increase in rate over the uncatalyzed reaction was observed when 1,10-phenanthroline was employed and near quantitative yields of arylation products were obtained (Equation (16)).44... 

Compare the base-catalyzed and acid-catalyzed mechanisms shown for keto-enol tautomerism. In base, the proton is removed from the a carbon, then replaced on oxygen. In acid, oxygen is protonated first, then the a carbon is deprotonated. Most proton-transfer mechanisms work this way. In base, the proton is removed from the old location, then replaced at the new location. In acid, protonation occurs at the new location, followed by deprotonation at the old location. 

Tautomerization is the shift of an H from a carbon adjacent to a carbon-heteroatom double bond to the heteroatom itself (and the reverse). It is an acid- or base-catalyzed equilibrium. Two examples are the keto/enol pair (Z = oxygen) and the imine/enamine pair (Z = nitrogen). Base catalysis goes via the enolate anion. 

Any reaction that simply involves the intramolecular transfer of a proton is called a tautomerism. Keto-enol interconversion may happen in basic as well as acidic solution. The steps are reversed in the base-catalyzed and acid-catalyzed reactions. In the base-catalyzed reaction, the first step is removal of an a-proton and the... 

The tautomerism is acid/base catalyzed and its rate controls the height of the more negative wave. The second reduction in the case R = phenyl can be identified with acetophenone but at a concentration determined by the rate of enolization to produce the keto form which is electroactive in the protonated condition. 

Ketones and aldehydes bearing a hydrogens are in equilibrium with their enol forms, although for simple ketones and aldehydes the carbonyl forms are greatly favored. This equilibrium is the keto—enol tautomerization. Equilibration with the enol form can be either acid- or base-catalyzed. The enol form can be favored in special cases. Esters and other acid derivatives also have acidic a hydrogens. LDA is a strong base that can be used to drive ketones, aldehydes, or esters completely to their corresponding enolates. 

As usual, this base-catalyzed reaction has its add-catalyzed counterpart. For the add-catalyzed reaction the catalyst is not hydroxide, but H30, and the active ingredient is not the enolate anion, but the enol itself The first step in the reaction is acid-catalyzed enol formation, the keto-enol tautomerization we have come to know (Fig. 19.67). 

In the first step of base-cataly2ed tautomerization of the keto form, hydroxide ion removes the a-hydrogen atom to give the enolate anion. Then, water reacts with the enolate anion to give the enol. To simplify the bond fine structures for the reaction, the step that forms the enolate shows one resonance form and the second step shows the alternate resonance form. Each of the reactions is reversible, so the base-catalyzed conversion of the enol into the keto form occurs by the reverse of each step of the mechanism. 

Know how to recognize or draw the keto and enol forms of a molecule, and know the mechanism of a keto-enol tautomerization under acid- and base-catalyzed conditions. 

Keto-enol tautomerism of carbon) ] compounds is catalyzed by both acids and bases. Acid catalysis occurs by protonation of the carbonyl oxygen atom to give an intermediate cation that Joses H+ from its a carbon to yield a neutral enol (Figure 22.1). This proton loss from the cation intermediate is similar to what occurs during an El reaction when a carbocation loses H+ to form an alkene (Section 11.10). 

In a number of nonenzymatic reactions catalyzed by pyridoxal, a metal ion complex is formed—a combination of a multivalent metal ion such as cupric oi aluminum ion with the Schiff base formed from the combination of an amino acid and pyridoxal (I). The electrostatic effect of the metal ion, as well as the electron sink of the pyridinium ion, facilitates the removal of an a -hydrogen atom to form the tautomeric Schiff base, II. Schiff base II is capable of a number of reactions characteristic of pyridoxal systems. Since the former asymmetric center of the amino acid has lost its asymmetry, donation of a proton to that center followed by hydrolytic cleavage of the system will result in racemic amino acid. On the other hand, donation of a proton to the benzylic carbon atom followed by hydrolytic cleavage of the system will result in a transamination reaction—that is, the amino acid will be converted to a keto acid and pyridoxal will be converted to pyridoxamine. Decarboxylation of the original amino acid can occur instead of the initial loss of a proton. In either case, a pair of electrons must be absorbed by the pyridoxal system, and in each case, the electrostatic effect of the metal ion facilitates this electron movement, as well as the subsequent hydrolytic cleavage (40, 43). 

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