Oxa-Diels-Alder

A DFT study on the oxa-Diels-Alder reaction of buta-1,3-diene with formaldehyde, catalysed by Co(II) and Co(III) complexes, has shown that axial coordination of an... 

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. 

A very recent study presented by Dujardin et al. describes the complementary use of chiral enol ethers as dienophiles in oxa Diels-Alder reactions. This approach has yielded promising results with regard to the synthesis of enantio-merically pure carbohydrates [481]. Further noteworthy studies directed to the preparation of biologically active amino sugars from enaminoketones have been carried out in our group [110]. 

Tetrahydroalstonine 7-7, a heteroyohimboid alkaloid, has been synthesised in enantiopure form by Martin et al. by means of an oxa Diels-Alder reaction as key step. The trienic precursor 7-5 underwent a thermal intramolecular cycloaddition to form a 5 1 mixture of 7-6 and its 15/J-epimer. The main cycloadduct was then subjected to a straightforward sequence to yield the natural product 7-7 (Fig. 7-2) [483-485]. In earlier work, Ogasawara et al. have employed a con-ceptionally different domino Knoevenagel-hetero Diels-Alder approach to this alkaloid and other natural products [486-488]. 

Spiroketals are not only important building blocks of polyethers but also may represent themselves highly active natural products. The suitability of oxa Diels-Alder reactions to efficiently generate this structure will be demonstrated by two impressive examples. Thus, our group prepared the mycotoxine (-)-talaromycin B 7-17 by a nine-step synthesis in 5% overall yield in enantiopure form. The... 

Beyond the hitherto discussed syntheses, there exist numerous further current and impressive applications of Diels-Alder reactions involving 1-oxa-1,3-butadienes which can only briefly be mentioned here due to the limits of space. Burke s group has developed an elegant retro-oxa Diels-Alder/all-carbon-Diels-Alder protocol which was employed as key step in the total syntheses of ( )-... 

Ohno M, Kojima S, Shirakawa Y, Eguchi S (1995) Tetrahedron Lett 36 6899 for similar oxa-Diels-Alder reaction leading to pyran-fused fullerenes see Ohno M, Azuma T, Eguchi S (1993) Chem Lett 1833... 

Asymmetric catalytic hetero Diels-Alder reactions give access to synthetically important substituted heterocycles [45]. Asymmetric oxa Diels-Alder reactions involving aldehydes and ketones and catalyzed by chiral Lewis acid catalysts can be performed with a high degree of chiral induction [46]. The field is much less advanced that of the corresponding catalytic enantioselective aza Diels-Alder reactions. 

Oxa-Diels-Alder reactions between l-oxy-3-silyloxybuta-1,3-dienes and aromatic aldehydes (either component being attached to a carbohydrate auxiliary) have been investigated by Stoodley et al. [109,110], drawing on the pioneering work of the Danishefsky group [111,112]. For example, the reaction of the carbohydrate-linked diene 143 with p-nitrobenzaldehyde in the presence of Eu(III) catalysts gave dihydropyrans 144-147 [109] (Scheme 10.47). When the chiral Eu complexes (- -)-Eu(hfc)3 and (—)-Eu(hfc)3 were used, double stereodifferentiation was... 

SCHEME 10.47 Sugar auxiliaries can influence the stereochemical outcome of oxa-Diels-Alder reactions. 

Lessman, T., Leuenberger, M. G., Menninger, S., Lopez-Canet, M., Muller, O., Hummer, S., Bormann, J., Korn, K., Fava, E., Zerial, M., Mayer, T. U., Waldmann, H. Natural product-derived modulators of cell cycle progression and viral entry by enantioselective oxa diels-alder reactions on the solid phase. Chem. Biol. 2007, 14, 443 51. 

Sanz, M. A., Voigt, X., Waldmann, H. Enantioselective catalysis on the solid phase synthesis of natural product-derived tetrahydropyrans employing the enantioselective oxa-Diels-Alder reaction. Adv. Synth. Cat. 2006,348, 1511-1515. 

Scheme 13. Oxa-Diels-Alder reaction between cyclopentadiene and glyoxylic acid...

The aqueous oxa-Diels-Alder reaction has been successfully exploited in the synthesis of sesbanimides A and B [70], carbovir [71], mevinic acids [72], aris-teromycin and carbodine [73], ketodeoxyoctulosonic acid (KDO) and analogs... 

Lessmann T, Leuenberger MG, Menninger S et al (2007) Natural Product-Derived Modulators of Cell Cycle Progression and Viral Entry by Enantioselective Oxa Diels-Alder... 

The organocatalysed asymmetric cycloaddition reaction of a,p-unsaturated ketones and aldehydes is scarcely studied, especially for fluorine-containing substrates. In this area, Liu et al. have reported unusual inverse-electron-demand oxa-Diels-Alder reactions of a,p-unsaturated trifluoromethyl ketones with aldehydes catalysed by chiral a,a-diphenylprolinol trimethylsilyl ether. It was shown that the addition of pura-fluorophenol and silica gel along with this catalyst was necessary, otherwise the reaction was very slow and a poor yield was obtained. Under these optimal conditions, the expected cyclic adducts were obtained in good yields and high fl n-diastereo- and enantioselectivities, as shown in Scheme 6.11. 

There are only few examples of asymmetric inverse hetero-Diels Alder reactions using a,P-unsaturated aldehydes. As a recent example, a cinchona alkaloid was successfully used to catalyse the oxa-Diels Alder reaction of heterodienes such as 3-formylchromones with acetylene dicarboxylates, providing the corresponding tricyclic benzopyrones in moderate to high yields (54-87%) and enantioselectivities (46-84% ee), as shown in Scheme 6.12. ... 

Oxa-Diels Alder reactions of a,p-unsaturated trifluoromethyl ketones... 

Scheme 6.12 Oxa-Diels-Alder reactions of 3-formylchromones with acetylene dicarboxylates.

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