Keto-enol tautomerization reactions generation

Phosphorylation, reduction, and tautomerization. Reaction of 3-phos-phoglycerate with ATP generates the corresponding acyl phosphate, which is reduced by NADH/H to an aldehyde. Keto-enol tautomerization of the aldehyde gives dihydroxyacetone phosphate, the same reaction as step 5 of glycolysis (F ure 29.4). 

Electrocyclic reactions are not limited to neutral polyenes. The cyclization of a pentadienyl cation to a cyclopentenyl cation offers a useful entry to five-membered carbocycUc compounds. One such reaction is the Nazarov cyclization of divinyl ketones. Protonation or Lewis acid complexation of the oxygen atom of the carbonyl group of a divinyl ketone generates a pentadienyl cation. This cation undergoes electrocyclization to give an allyl cation within a cyclopentane ring. The allyl cation can lose a proton or be trapped, for example by a nucleophile. Proton loss occurs to give the thermodynamically more stable alkene and subsequent keto-enol tautomerism leads to the typical Nazarov product, a cyclopentenone (3.220). 

When 1-hexyne is treated with a catalytic amount of sulfuric acid in an aqueous solvent, initial reaction with the acid gives the expected secondary vinyl carbocation 103, and the most readily available nucleophile in this reaction is water (from the aqueous solvent). Nucleophilic addition of water to 103 leads to the vinyl oxonium ion 104. Loss of a proton in an acid-base reaction (the water solvent is the base) generates a product (105) where the OH unit is attached to the C=C unit, an enol. Enols are unstable and an internal proton transfer converts enols to a carbonyl derivative, an aldehyde, or a ketone. This process is called keto-enol tautomerization and, in this case, the keto form of 105 is the ketone 2-hexanone (106). (Enols are discussed in more detail in Chapter 18, Section 18.5.) Note that the oxygen of the OH resides on the secondary carbon due to preferential formation of the more stable secondary carbocation followed by reaction with water, and tautomerization places the carbonyl oxygen on that same carbon, so the product is a ketone. When a disubstituted alkyne reacts with water and an acid catalyst, the intermediate secondary vinyl cations are of equal stability and a mixture of isomeric enols is expected each will tautomerize, so a mixture of isomeric ketones will form. 

This map indicates that the acyl carbon and the carbon atom at the end of the C=C unit (resonance contributors 37B and 37C) are most likely to react with chloride ion to form a product. If chloride ion reacts at the terminal carbon (37C), the product is an enol, which tautomerizes to the final product, 39. Keto-enol tautomerization was introduced in Chapter 10 (Section 10.4.5) and discussed again in Chapter 22 (Section 22.1). An alternative mechanism is possible in which HCl reacts with the C=C unit of 10 to generate 38 directly, and subsequent reaction with chloride ion gives 39. Experimental evidence suggests that 37 is the more likely intermediate that leads to 39. 

Trifluoroacetylketene (91) has been generated in aqueous solution by flash photolysis. Rates of hydration to form the enol of 4,4,4-trifluoroacetoacetic acid (92e) have been measured, and also rates of the subsequent ketonization to the /3-keto acid (92k). Extensive rate and equilibrium constant data are reported for these reactions and for the ionizations of the tautomers. For example, the enol (92e) has acidity constants (in -logio form) of 1.85 and 9.95, for the acid and enol OH groups, respectively. Rates of enolization of (92k) have also been measured (by bromination) and, combined with an estimate of the hydration constant (K = 2900) of (92k), suggest that the keto-enol tautomeric constant is ca 0.5, about 100 times greater than that of its unfluorinated analogue. 

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