Hemiketal ring formation

The concentration of ascorbic acid in milk (11.2-17.2mgl-1) is sufficient to influence its redox potential. In freshly drawn milk, all ascorbic acid is in the reduced form but can be oxidized reversibly to dehydroascorbate, which is present as a hydrated hemiketal in aqueous systems. Hydrolysis of the lactone ring of dehydroascorbate, which results in the formation of 2,3-diketogulonic acid, is irreversible (Figure 11.2). 

Alcohols, amines, and thiols add readily to the electrophilic carbon of the carbonyl group to form hemiacetals, carbinolamines, hemiketals, and hemimercaptals. An example is the formation of ring structures of sugars (Eq. 4-1). Water can also add to carbonyl groups and most aliphatic carbonyl compounds... 

Although the spectral properties of cyclopropanones and the easy formation of hydrates and hemiketals are inconsistent with the dipolar form, some reactions of cyclopropanones do indicate that the ring carbons are much more electrophilic than in other cyclic or acyclic ketones. For example, nucleophilic ring opening often occurs easily ... 

In accord with the above, substituent effects in 2-arylcyclopropanone hemiketals indicate that initial conversion to the parent ketone takes place prior to a C2—C3 ring opening. 16> Although hemiketal-ketone equilibration is slow under neutral conditions, ketone formation and hence cleavage through 130 is accelerated in acid. 

Pretazettine (242) has a trans B-D ring juncture and seems a fairly strained molecule whereas tazettine (240) bears a cis B-D fusion allowing more flexibility, and the driving force for the B-ring opening is attributed to the relief of this internal strain. The reaction would be completed by an intramolecular crossed Cannizzaro reaction followed by hemiketal formation yielding the cis B-D fusion present in 242. 

Fig. 9.7. Stereochemistry of the hemiketal formation from D-fructose in aqueous solution at 25°C (in the formulas for the six-membered ring hemiketal the carbon skeleton of 5-valerolactol is black, which emphasizes the relationship to the reaction from Figure 9.5, whereas the extra substituents as well as the bonds leading to them are red).

Monosaccharides Form Rings as a Consequence of Internal Hemiacetal or Hemiketal Formation. 

Nakamura, S., Inagaki, J., Kudo, M., Sugimoto, T, Ohara, K., Nakajima, M. and Hashimoto, S., 2002. Studies directed toward the total synthesis of pinnatoxin A synthesis of the 6,5,6-dispiroketal (BCD ring) system by double hemiketal formation/hetero-Michael addition strategy. Tetrahedron 58, 10353-10374. 

Figure 11.5. Furanose Formation. The open-chain form of fructose cyclizes to a five-membered ring when the C-5 hydroxyl group attacks the C-2 ketone to form an intramolecular hemiketal. Two anomers are possible, but only the a anomer is shown.

Recent evidence for the formation of hemiketal intermediates iqmn acylation of alkynides has been obtained from glucopyranolactones. Treatment of tetrabenzyl (55) with the anion from l-benzyloxy-3-bu-tyne gave a quantitative yield of hemiketal (56) which showed IR absorptions for the OH and alkyne portions of the molecule (X = 3350 cm" and 2250 cnr, respectively). This compound was stereospecifi-cally reduced to the C-glycoside (57) with triethylsilane/BFs-etherate (overall yield 72% Scheme 18). None of the other stereoisomer or ring-opened product was obtained. ... 

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