Carbohydrates hetero Diels-Alder reaction

Scheme 2.170. Domino Knoevenagel/hetero-Diels-Alder reaction of aldehydes derived from carbohydrates.

For the generation of several contiguous chiral centers, two alternative key step reactions can be applied (i) stereoselective CC-bond formation and (ii) stereoselective functionalization of compounds having already the required carbon skeleton. In the de novo-synthesis of carbohydrates and related natural products via inverse-type hetero-Diels-Alder reactions both of these principles are especially well documented as will be shown below (8-10). ... 

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). 

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 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. 

The advanced state of the art in carbohydrate synthesis basing on hetero Diels-Alder reactions of 1-oxa-l,3-butadienes has opened an access to enan-tiopure sugar derivatives. Thus, our group found the cycloaddition of the chiral heterodiene 7-1 and the electron-rich alkene 7-2 under the influence of Me2AlCl to give the dihydropyran 7-3 in excellent endo selectivity (endo/exo >50 1) and as well excellent induced diastereoselectivity (54 1) [478]. A short sequence involving one simple recrystallisation then led to the ethyl-/)-D-mannopyrano-side 7-4 in enantiomerically pure form (Fig. 7-1). 

Hetero Diels-Alder reactions with imino dienophiles have been employed as key step in several syntheses of naturally occuring alkaloids. With regard to stereoselective transformations, the approach to (S)-anabasin worked out by Kunz et al. impressively illustrates the high utility of natural carbohydrates as source of chirality in asymmetric synthesis [505]. The N-galactosyl imine 7-28 underwent a Lewis acid catalysed aza Diels-Alder reaction with Danishefsky s diene which proceeded with excellent induced diastereoselectivity to yield the adduct 7-29. A short sequence then afforded the desired alkaloid 7-30. This work also deals with the suitability of several other dienes and imino dienophiles for such transformations (Fig. 7-7). 

Schmidt, R R, Frick, W, Haag-Zeino, B, Apparao, S, De-novo synthesis of carbohydrates and related natural products. Part 28. C-arylglycosides and 3-deoxy-2-glyculosonates via inverse type hetero-Diels-Alder reaction, Tetrahedron Lett., 28, 4045 -4048, 1987. 

Carbohydrate-Linked Dipolarophiles [4 + 2] Cycloadditions (Diels-Alder Reactions) Hetero Diels-Alder Reactions... 

SCHEME 10.46 Carbohydrate-directed hetero Diels-Alder reactions with aza-dienophiles. 

Pfrengle, W, Kunz, H, Hetero Diels-Alder reactions on a carbohydrate template stereoselective... 

Tietze, L F, Schneider, C, Montenbiuck, A, Asymmetric 1,6-induction in hetero-Diels-Alder reactions of chiral oxabutadienes for a de novo synthesis of enantiomerically pure carbohydrates Lewis acid dependent reversal of facial selectivity, Angew. Chem. Int. Ed. Engl., 33,980-982, 1994. 

Several diastereoselective HDA (hetero-Diels-Alder) reactions of a,/3-unsaturated carbonyl compounds and electron-rich alkenes have been exploited to gain carbohydrate derivatives with good diastereomeric excess. In HDA reaction, up to three chiral centers are formed with high stereoselectivity at each chiral carbon [78]. 

There are also special procedures which allow the preparation of sugars with only endo- or only exo-cyclic double bonds. The first group of compounds with endo-cyclic double bond may be prepared by total synthesis from non-carbohydrate precursors. The particularly useful hetero Diels-Alder reaction (O Fig. 3) allows one to obtain the dihydropyran skeleton either by reaction of a diene with a heterodienophile [3,17] or by reaction of a heterodiene with a normal dienophile [18]. 

Zamojski, A. De novo synthesis of enantiopure carbohydrates preparation of ethyl (i-D- and 3-L-mannopyranosides by an asymmetrically induced hetero Diels-Alder reaction. Chemtracts Org. Chem. 1995, 8, 69-72. 

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. 

Pfrengle, W, Kunz, H, Hetero Diels-Alder reactions on a carbohydrate template stereoselective synthesis of (S)-anabasine, J. Org. Chem., 54, 4261-4263, 1989. 

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