Aldehydes reactions with activated dienes

Midland has used the cyclocondensation reaction with activated dienes to synthesize pstelotin A (165 Scheme 45). The key step in the Midland synthesis is the ACF addition of diene (162) with aldehyde (161) to give (164), using Eu(hfc)3 as catalyst. Deprotection of the benzyl group gave the target molecule (165). 

Chiral boron(III) Lewis acid catalysts have also been used for enantioselective cycloaddition reactions of carbonyl compounds [17]. The chiral acyloxylborane catalysts 9a-9d, which are also efficient catalysts for asymmetric Diels-Alder reactions [17, 18], can also catalyze highly enantioselective cycloaddition reactions of aldehydes with activated dienes. The arylboron catalysts 9b-9c which are air- and moisture-stable have been shown by Yamamoto et al. to induce excellent chiral induction in the cycloaddition reaction between, e.g., benzaldehyde and Danishefsky s dienes such as 2b with up to 95% yield and 97% ee of the cycloaddition product CIS-3b (Scheme 4.9) [17]. 

Danishefsky et al. were probably the first to observe that lanthanide complexes can catalyze the cycloaddition reaction of aldehydes with activated dienes [24]. The reaction of benzaldehyde la with activated conjugated dienes such as 2d was found to be catalyzed by Eu(hfc)3 16 giving up to 58% ee (Scheme 4.16). The ee of the cycloaddition products for other substrates was in the range 20-40% with 1 mol% loading of 16. Catalyst 16 has also been used for diastereoselective cycloaddition reactions using chiral 0-menthoxy-activated dienes derived from (-)-menthol, giving up to 84% de [24b,c] it has also been used for the synthesis of optically pure saccharides. 

Diels-Alder reaction of aldehydes with activated dienes. This lanthanide shift reagent can function as a Lewis acid catalyst in the cyclocondensation of l-methoxy-3-trimethylsilyloxy-1,3-diene (2) with aromatic aldehydes, and permits isolation of the initial... 

The modified organoaluminum reagent, BINAL, can be used as a chiral Lewis acid catalyst in the asymmetric hetero-Diels-Alder reaction [41]. Reaction of various aldehydes with activated dienes under the influence of catalytic BINAL (5-10 mol%) at -20 °C gave, after exposure of the resulting hetero-Diels-Alder adducts to tri-fluroacetic acid, predominantly c/v-dihydropyrone in high yield with excellent enan-tioselectivity. 

The reaction of activated dienes with aldehydes is emerging as a powerful tool in the synthesis of natural products. This chapter reviews the major contributions that have led to the discovery and use of this reaction in organic synthesis. The first part of the chapter discusses the mechanism of the reaction, the second part describes the use of chiral aldehydes, chiral dienes and chiral catalysts in controlling stereochemistry, and the last section outlines applications in the synthesis of natural products. 

A variety of methods are now available to control the relative and absolute stereochemistry of the cyclocondensation reaction of activated dienes with aldehydes. Chiral aldehydes that posses a high degree of diastereofacial selectivity with a variety of dienes can be used and the stereoselectivity controlled by the choice of diene, aldehyde and catalyst. Chiral dienes in combination with chiral catalysts can also be used in an unusual process of double diastereofacial selectivity. The resulting adducts can be purified and eliminated to give optically pure dihydropyrones. The chiral auxiliary can be isolated and reused if... 

The most straightforward application of the cyclocondensation reactions of aldehydes with activated dienes is in the synthesis of simple monosaccharides.- Condensation of diene (100) with benzyloxyacet-aldehyde (9a) using Bp3-Et02 as a catalyst, followed by treatment with TFA, gives the dihydropyrone (102). Reduction of (102) using DIBAL-H followed by hydroxylation of the glycal gives, after deprotection, talose (103 Scheme 30). 

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