Chiral cyclized hemiacetal

Aldoses exist almost exclusively as their cyclic hemiacetals very little of the open chain form is present at equilibrium To understand their structures and chemical reac tions we need to be able to translate Fischer projections of carbohydrates into their cyclic hemiacetal forms Consider first cyclic hemiacetal formation m d erythrose To visualize furanose nng formation more clearly redraw the Fischer projection m a form more suited to cyclization being careful to maintain the stereochemistry at each chirality center... 

An interesting variant involves the use of an allylic alcohol as the alkene component. In this process, re-oxidation of the catalyst is unnecessary since the cyclization occurs with /Uoxygen elimination of the incipient cr-Pd species to effect an SN2 type of ring closure. Both five- and six-membered oxacycles have been prepared in this fashion using enol, hemiacetal, and aliphatic alcohol nucleophiles.439,440 With a chiral allylic alcohol substrate, the initial 7r-complexation may be directed by the hydroxyl group,441 as demonstrated by the diastereoselective cyclization used in the synthesis of (—)-laulimalide (Equation (120)).442 Note that the oxypalladation takes place with syn-selectivity, in analogy with the cyclization of phenol nucleophiles (1vide supra). 

Takano s group reported the first enantioselective total synthesis of (—)-anti-rhine as well (146). Chiral product 235 was prepared via a number of stereoselective reactions. Reductive condensation of 235 with tryptamine, using sodium cyanoborohydride at pH 6, supplied lactam 236, which was reduced by di-isobutylalminum hydride to hemiacetal 237. The latter could be cyclized to (-)-antirhine by simple acid treatment (146). 

An intriguing synthesis of chiral cyclopentenone [100] from D-glucose has recently been described (53). The readily available diacetone glucose [94] was benzylated, selectively deprotected, and oxidatively cleaved to the aldehyde, which was condensed with nitromethane to adduct [95]. Acidic hydrolysis of the product gave hemiacetal [96], cleaved with periodate in methanol to aldehyde [97], Aldol-type cyclization was effected with triethylamine subsequent dehydration to [98] was induced by mesyl-ation. The nitro olefin [98], upon treatment with activated lead in an acidic media, was converted to ketone [99], Mesylation in the presence of triethylamine then led directly to cyclopentenone [100],... 

Monosaccharides normally exist as cyclic hemiacetals rather than as open-chain aldehydes or ketones. The hemiacetal linkage results from reaction of the carbonyl group with an -OH group three or four carbon atoms away. A five-membered cyclic hemiacetal is called a furanose, and a six-membered cyclic hemiacetal is called a pyranose. Cyclization leads to the formation of a new chirality center and production of two diastereomeric hemiacetals, called a and p anomers. 

There are four chiral centers in the openchiral center at the carbon involved in hemiacetal formation, giving a total of five chiral centers in the cyclic form. 

Cyclization produces two stereoisomeric hemiacetals, called anomers. The newly created chirality center is called the anomeric carbon. 

Although many of the properties of D-(-l-)-glucose can be explained in terms of an open-chain structure (1,2, or 3), a considerable body of evidence indicates that the open-chain structure exists, primarily, in equilibrium with two cyclic forms. These can be represented by structures 4 and 5 or 6 and 7. The cyclic forms of D-(+)-glucose are hemiacetals formed by an intramolecular reaction of the —OH group at C5 with the aldehyde group (Fig. 22.4). Cyclization creates a new chirality center at Cl, and this chirality center explains how two cyclic forms are possible. These two cyclic forms are diastereomers that differ only in the configuration of C1. 

When an open-chain monosaccharide cyclizes to a pyranose form, a new chirality center is generated at the former carbonyl carbon and two diastereo-mers, called anomers, are prodnced. The hemiacetal carbon atom is referred... 

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