Carbohydrate dienophiles cycloadditions

Carbohydrate Dienophiles. The most popular carbohydrate dienophiles to date have been pyranoid enones. Examples of Diels-Alder reactions involving carbohydrate 2,3-enones, 3,4-enones, and enolone esters are described below. In landmark studies reported by Fraser-Reid and co-workers, carbohydrate-derived 2,3-enones were shown to react with dienes to give cyclohexopyranosides (7- 3), Derivatives of methyl and ethyl 2,3-dideoxy- a D-g/ycero-hex-2-enopyranosid-4-ulose 1 underwent cycloaddition with butadiene in the presence of aluminum chloride, and with oxygen -substituted dienes in the absence of any catalyst. Annulated pyranosides 2 and 3 were obtained... 

Further reactions that are highly suited to the synthesis of cyclohexane derivatives, such as cycloaddition processes, 1,3-dipolar additions, and Diels-Alder cyclizations, have been used extensively. In the latter set, carbohydrate-based dienes or dienophiles have been employed and, in addition, intramolecular processes have provided highly suitable means of synthesizing complex polycyclic systems. 

An attractive entry to the carbohydrate synthesis is provided by the cycloaddition reaction. Hetero-Diels-Alder reaction, either between an oxa-diene (a,[3-unsaturated aldehyde) and an nucleophilic dienophile, or between activated diene and carbonyl compound (usually an aldehyde), leads to dihydropyrans, which can be subsequently functionalized to sugars in the desired manner (Scheme 3). 

The dihydropyrans resulting from an oxa Diels-Alder reaction represent valuable intermediates for the synthesis of numerous natural compounds. In particular, they exhibit many structural elements of carbohydrates. It is therefore not surprising that both the normal electron demand cycloaddition of dienes to carbonyl dienophiles as well as the reaction of 1-oxa-l,3-butadienes with electron-rich alkenes have extensively been used for the synthesis of sugar derivatives. Nevertheless, various approaches to other natural products have been worked out by means of these powerful tools. 

The inverse electron demand hetero Diels-Alder reaction of 1-oxa-l,3-butadienes and electron-rich dienophiles is an extremely versatile tool in natural product synthesis. This cycloaddition represents the key step of numerous approaches not only to carbohydrates, but also to terpenes, alkaloids, polyethers, steroid derivatives and various biologically active metabolites. 

Horton et al. were interested in the synthesis of tetra-C-substituted carbocycles, and extensively studied asymmetric Diels-Alder reactions employing acyclic unsaturated carbohydrate derivatives. Thus, the thermal cycloaddition of the D-arabinose-derived c/i-dienophile (Z)-100 with cyclopentadiene gave endo-adduct 101 in excellent optical purity. The high diastereo-facial differentiation in this reaction arises from a highly favored conformation at the allylic center [76,77] (Scheme 10.33). Therefore, conformer 102 seems to be more favored than 103, where the latter suffers from severe allylic strain between the methoxycarbonyl and the C4-acetoxy group... 

Horton, D, Koh, D, Takagi, Y, Stereocontrol in Diels-Alder cycloaddition to unsaturated sugars reactivities of cw-dienophiles with cyclopentadiene, Carbohydr. Res., 250, 261-274, 1993. 

Cycloadditions are widely used methods for carbocycle construction [352], In this context, the Diels-Alder reaction has been studied in carbohydrate chemistry. Using this approach, the sugar can be used as the dienophile or as the diene with a large preference for the former. 

The application of cyclic carbohydrate derivatives as chiral dienophiles has been investigated by several groups. 2,3-Dideoxy-DL-pent-2-enopyranose-4-ulose (17) in the thermal [4+2] cycloaddition to the acyclic dienes 18a-c is reported to produce mixtures of cycloadducts 19a-c epimeric on the hemiacetal center with an all-as-configuration of the other newly formed bonds. The reaction with cyclopentadiene (10) and 1,3-cyclohexadiene (11) yields adducts 20 as the sole products31. It should be emphasized that epimerization may occur on the anomeric center during the protection step (as an equilibrium process), thus leading to a mixture of adducts, while the endolexo ratio remains the same. 

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