15.1:
Reactivity of Enols
Enols, the tautomers of carbonyl compounds, are nucleophilic in nature owing to their electron-rich double bonds.
In addition, the electron-donating resonance effect of the adjacent hydroxyl group leads to substantially greater electron density on the α carbon, making it more reactive than the corresponding alkene.
Enols are key reactive intermediates in reactions at the α carbon, like α-halogenation.
Typically, the nucleophilic α-carbon atom of an enol attacks an electrophile, creating a resonance-stabilized cation intermediate with a new bond on the α carbon. Subsequent deprotonation yields a neutral α-substituted product.
This reaction pathway is distinct from that of alkenes, where cation intermediates react with nucleophiles to form addition products.
In addition, enolization is characterized by reversible proton transfer at the α carbon, as seen in deuterium exchange experiments.
As enols are achiral at the α carbon, this leads to slow racemization of keto compounds with chiral α carbon centers.
15.1:
Reactivity of Enols
Enols are a class of compounds where a hydroxyl group is attached to a carbon–carbon double bond, which implies that it is a vinyl alcohol. A carbonyl compound with an α hydrogen undergoes keto–enol tautomerism and remains in equilibrium with its tautomer, the enol form. Usually, the keto tautomer is present in a higher concentration than the enol tautomer due to the higher bond energy of C=O compared to C=C. Moreover, the direction of the keto–enol equilibrium is governed by factors like conjugation, intramolecular hydrogen bonding, and aromatic energy. Recall that tautomers are constitutional isomers with distinct atomic arrangements, while resonance forms are different representations of one molecule. This tautomerization is reversibly catalyzed by both acids and bases involving protonation and deprotonation steps. While protonation precedes deprotonation in presence of an acid leading to enols, the reverse order is followed in base-catalyzed enolization that yields enolates.
Enols are electron-rich and hence nucleophilic in nature, like other compounds containing carbon–carbon double bonds. Due to the strong electron-donating resonance effect of the hydroxyl group, a second resonance structure of the enol can be drawn where the negative charge is on the α carbon. Consequently, this carbon atom is especially nucleophilic and reacts with electrophiles (E+) to form a new C–E bond. Loss of a proton in the next step leads to a neutral product. The net result amounts to the substitution of hydrogen by an electrophile on the α carbon. Therefore, carbonyl compounds are halogenated at the α position by halogens, such as bromine, in both acidic and basic solutions. This results in the formation of different products under various reaction conditions.
When a carbonyl compound with at least one α hydrogen is dissolved in D2O, to which DCl or NaOD are added, the α hydrogens are gradually replaced by deuterium (D) atoms via enol formation. If this carbonyl compound is chiral owing to a stereogenic center at the α carbon, its chirality is destroyed by rapid interconversion between keto and enol forms through a planar, achiral enol intermediate. The spontaneous racemization prevents the synthesis of chiral ꞵ-keto esters whose only stereogenic center lies in between the two keto groups.
Suggested Reading
- Solomons, G., & Fryhle, C. & Snyder, S. (2015). Organic Chemistry. New Jersey, NJ: Wiley, 822.
- Loudon, M., & Parise, J. (2016). Organic Chemistry. New York, NY: Macmillan Publishers, 1103.
- Clayden, J., & Greeves, N., & Warren, S. (2012). Organic Chemistry. Oxford: Oxford University Press, 449.
- Carey, F. A. (2000). Organic Chemistry, McGraw-Hill, 702.
- McMurry, J. (2016). Organic Chemistry. Cengage Learning. Boston. MA. 728.
- Smith, J. G. (2008) Organic Chemistry, McGraw Hill, 884.