Intramolecular hemiketals

In a similar manner, ketones can react with alcohols to form hemiketals. The analogous intramolecular reaction of a ketose sugar such as fructose yields a cyclic hemiketal (Figure 7.6). The five-membered ring thus formed is reminiscent of furan and is referred to as a furanose. The cyclic pyranose and fura-nose forms are the preferred structures for monosaccharides in aqueous solution. At equilibrium, the linear aldehyde or ketone structure is only a minor component of the mixture (generally much less than 1%). 

The aldehyde or ketone group of monosaccharides can undergo an intramolecular reaction with one of its own hydroxyl groups to form a cyclic, hemiacetal, or hemiketal structure, respectively (Figure 1.26). In aqueous solutions, this cyclic structure actually predominates. The open-chain aldehyde or ketone form of monosaccharides is in equilibrium with the cyclic form, but the open structure exists less than 0.5 percent of the time in aqueous environments. It is the... 

The preference for the /3-silyl isomer product complements methods available for hydrostannation of alkynes, for which the a-stannyl regioisomer is formed preferentially.70 7011 70c In addition, the /3-silyl products serve as the platform for a tertiary alcohol synthesis (Scheme 15). Upon treatment of vinylsilanes such as B with tetrabutylam-monium fluoride (TBAF) in DMF at 0 °C, a 1,2 carbon-to-silicon migration occurs, affording the tertiary heterosilane E. Oxidation of the C-Si bond then provides the tertiary alcohol. Good 1,2-diastereocontrol has been demonstrated for y-alkoxy substrates, as in the example shown. The studies suggest that the oxidation of the sterically demanding silane intermediate is facilitated by the intramolecular formation of a silyl hemiketal or silyllactone for ketone or ester substrates, respectively.71... 

Ring-chain tautomerism in which a ring closure occurs via intramolecular addition of an OH group to a C=0 bond (Scheme 4) is observed widely in organic chemistry. This type of tautomerism is sometimes called ketolo-lactolic, keto-lactolic, or oxo-cyclo tautomerism. The ring tautomers are usually referred to as cyclic hemiacetals or hemiketals. 

The proposed mechanism for these reactions is shown in Scheme 13.96 [106], The initial formation of hemiketal 262 is followed by loss of water and generation of oxonium cation 263. Subsequent intramolecular addition of the azide function onto the cation produces intermediate 264. Elimination of a proton and of N2 directly affords the heterocyclic products. An alternative mechanism involving a... 

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. 

In 1993, Molander found that in the presence of catalytic Fe(III) salts, Sml2 mediates intramolecular Barbier additions to esters to give cyclic ketones (or cyclic hemiketals, if they prove to be stable).135 Double addition to the ester is not observed, nor is reduction of the cyclic ketone product. This suggests that the tetrahedral intermediate, a samarium alkoxide of a cyclic hemiketal, is partially stable to the reaction conditions and the ketone group is not revealed until work-up. Molander found that both alkyl and allyl halides could be used in the additions (Scheme 5.83).135... 

The organoselenium-mediated intramolecular trapping of a hemiketal by a suitably disposed carbon-carbon double bond can lead to a spiroketal, although with low stereoselectivity. Thus, when 9-hydroxy-l-nonen-5-one (17) is treated with /V-(phenylsclcno)phthalimide and a catalytic amount of zinc bromide in dichloromethane at 20 °C, a 67 33 (ZjE) mixture of the seleno derivatives is obtained in 78% yield. After Raney nickel reduction, the corresponding spiroketals are recovered in 90% yield103-104. 

For an aldohexose such as glucose, the C-1 aldehyde in the open-chain form of glucose reacts with the C-5 hydroxyl group to form an intramolecular hemiacetal. The resulting cyclic hemiacetal, a six-membered ring, is called pyranose because of its similarity to pyran (Figure 11.4). Similarly, a ketone can react with an alcohol to form a hemiketal. 

The C-2 keto group in the open-chain form of a ketohexose, such as fructose, can form an intramolecular hemiketal by reacting with either the C-6 hydroxyl group to form a six-membered cyclic hemiketal or the C-5 hydroxyl group to form a five-membered cyclic hemiketal (Figure 11.5). The five-membered ring is called a furanose because of its similarity to... 

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.

In the lactone acylations discussed above, there was never any evidence for a competing side reaction due to break down of the hemiketal moiety and Michael addition of the alcohol to the newly formed pro-pargylic ketone. This may be taken as filler evidence for the stability of the ketal-alkoxide intermediate however, hemiketal ring opening and intramolecular Michael addition would provide an... 

Under acidic conditions erythromycin can undergo spontaneous intramolecular ring cy-clizations, the products of which are inactive (96-99). All contain either the 6,9-hemiketal or the 8,9-anhydro-6,9-hemiketal they may also contain the 6,9 9,12-spiroketal. The synthesis and isolation of the biologically active... 

Hemiacetals and hemiketals are readily formed in carbohydrates. Monosaccharides contain several hydroxyl groups and one carbonyl group. The linear form of a monosaccharide quickly undergoes an intramolecular reaction in solution to give a cyclic hemiacetal or hemiketal. 

Fructose is a ketose, or ketone sugar. Recall that the reaction between an alcohol and a ketone )delds a hemiketal. Thus the reaction between the C-2 keto group and the C-5 hydroxyl group in the fructose molecule produces an intramolecular hemiketal. Fructose forms a five-membered ring structure. 

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