Carbohydrate chemistry Diels-Alder reactions

Y. Chapleur and M.-N. Euvrard, Hetero Diels-Alder reactions in carbohydrate chemistry A new strategy for multichiral arrays synthesis, J. Chem. Soc. Chem. Commun. p. 884 (1987). 

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. 

Osborn, H. M. I., Coisson, D. Application of the asymmetric hetero diels-alder reaction for synthesising carbohydrate derivatives and glycosidase inhibitors. Mini-Reviews in Organic Chemistry 200i, 1,41-54. 

A review of cycloaddition reactions in carbohydrate chemistry is presented. The use of carbohydrate-derived dienes and dienophiles in the Diels-Alder reaction, hetero-Diels-Alder and dipolar addition reactions of carbohydrates are described. Stereochemical aspects of the cycloaddition processes are also discussed, and applications to the synthesis of natural products are included for each reaction type. Much of the material presented has appeared in the literature within the past five years however, earlier studies are also included in order to give a more representative historical perspective. 

Cationic zirconocenes serve as useful reagents in such diverse fields as alkene polymerization, carbohydrate chemistry, asymmetric catalysis, and so on. Reagents that were originally developed for polymerization reactions (MAO, ansa-metallocenes, non-nucleophi-lic borate counterions) have now found use in organic synthesis and are being employed for carbometalation reactions, hydrogenation, and Diels—Alder catalysis. 

J. C. Lopez and G. Lukacs, Pyranose-derived dienes and conjugated enals—preparation and Diels-Alder cycloaddition reactions, in Cycloaddition Reactions in Carbohydrate Chemistry, 1992, pp. 33-49. 

Another annellation reaction starts from a,a -dibromo-o-xylene, an activated olefin and zinc.63 This reaction, according to the authors proceeds by a Diels-Alder cycloaddition via the o-xylylene (Scheme 15.10), and was employed in carbohydrate chemistry to prepare anthracyclinones analogues.64 No reaction occurs without sonication. Instead of a cycloaddition, another explanation can be postulated, consisting first of addition of a mono-organozinc reagent to the activated olefin, followed by alkylation of the resulting enolate by the second benzylic bromide. 

Although carbohydrates are cheap and readily available chiral compounds, their application in stereoselective synthesis was for a long time limited to ex-chiral-pool syntheses [3]. They have been considered too complex compared to other chiral auxiliaries, for example a-pinene in borane-chemistry [4] or BINAP-derivatives in reduction chemistry [5]. However, it has been shown during the past few years that carbohydrates can be successfully applied as stereodifferentiating tools in many different reaction types such as aldol- [6], hydrogenation- [7], carbonyl addition- [8], Michael- [9], Diels-Alder- [10], hetero-Diels-Alder [11], and rearrangement reactions [12]. 

The pr e-Woodwardhn era largely concerned itself with the collection and classification of synthetic tools chemical reactions suited to broad application to the constitutional construction of molecular skeletons (including Kiliani s chain-extension of aldoses, reactions of the aldol type, and cycloadditions of the Diels-Alder type). The pre- Woodwardian era is dominated by two synthetic chemists Emil Fischer and Robert Robinson. Emil Fischer was emphasizing the importance of synthetic chemistry in biology as early as 1907 [30]. He was probably the first to make productive use of the three-dimensional structures of organic molecules, in the interpretation of isomerism phenomena in carbohydrates with the aid of the Van t Hoff and Le Bel tetrahedron model (cf. family tree of aldoses in Scheme 1-6), and in the explanation of the action of an enzyme on a substrate, which assumes that the complementarily fitting surfaces of the mutually dependent partners are noncovalently bound for a little while to one another (shape complementarity) [31],... 

Regioselective reductions of a,P-imsaturated ketones were performed in water containing carbohydrate-derived amphiphiles. Cyclohexenones were converted to allylic alcohols, whereas cyclopentenones gave substantial amounts of 1,4-reduction (Denis et al, 1996). Such a use of concentrated aqueous solutions of carbohydrates as the reaction medium has been described by Lubineau (1993, 1994b) in the context of many different chemical transformations including Diels-Alder, aldol and Michael reactions, as well as reductions of a,p-unsaturated ketones, all dealing with the chemistry of the carbonyl group either as the reaction site or as the activation site (Scheme 4.17). 

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