Syntheses with Oxa Diels-Alder Reactions

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. 

In early work which have been summarized very recently [23], Danishefsky et al. have investigated hetero Diels-Alder reactions of carbonyl compounds in order to yield glycals. Numerous further contributions to the stereoselective synthesis of dihydropyran derivatives by high pressure or Lewis acid induced Diels-Alder reactions of carbonyl compounds have been made by Jurczak et al., 

This methodology which bases on Oppolzer s sultams has also been employed in the synthesis of 2,6-N,N-diacetyl-D-purpurosamidine C [475,476]. Hetero Diels-Alder reactions of carbonyl dienophiles are furthermore involved in the preparation of ( )-ketoheptulosic acid [477] and in the already mentioned asymmetric approach to the C-26-C-32 tetrahydropyran subunit of swinholide A [92]. 

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). 

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