Knoevenagel-carbon-Diels-Alder Reactions

Domino-Knoevenagel-carbon-Diels-Alder Reactions 

The alkylidene- or benzylidene-1,3-dicarbonyl compounds formed in the Knoevena-gel condensation of aldehydes or ketones with 1,3-dicarbonyls, can act not only as a 

162 5 The Domino-Knoevenagei-hetero-Diels-Alder Reaction and Related Transformations 

9 Tietze, L. F., Steck, P. High Pressure Chemistry, Eldik, R., Klarner, F. G., eds. Wiley-VCH, Weinheim, 2002, pp. 239-283. 

Kitajima, M., Aimi, N., Konno, K., Inoue, H., Fujiwara, M., Mizuta, T., Yokota, T., Shigeta, S., Tokuhisa, 

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Domino-Knoevenagel-carbon-Diels-Alder Reactions... 

What is described as a domino Knoevenagel-hetero-Diels-Alder reaction , involving the reaction of the glucose-derived aldehyde 93 with a 1,3-dicarbonyl compound in presence of either proline or ethylenediammonium acetate, leads to the doubly annulated 5 6 6-fused compound 94 (Scheme 30) <2004S1150>. If the dicarbonyl compound is Meldmm s acid, however, the sequence is completed by spontaneous elimination of acetone and carbon dioxide from the Diels-Alder adduct, to give compound 95 <2005ASC1353>. 

We have been particularly enamored with the development of experiments involving carbon-carbon bond formation, especially as part of tandem reactions occurring in a single container (see the Diels-Alder reaction. Figure 1). One such reaction is the synthesis of simple esters of coumarin-3-carboxylic acids via a Knoevenagel condensation between malonic esters and various a-hydroxybenzaldehydes, followed by intramolecular nucleophilic acyl substitution. This conversion, catalyzed by piperidine, has been carried out under a variety of conditions, for example, at room temperature without solvent... 

Deoxyloganin (24) has previously been synthesized by Tietze and coworkers, utilizing an intramolecular hetero-Diels-Alder reaction to construct the iridoid core (Scheme 10). The synthesis commenced with conversion of (5)-citronellal (47) to enol ether 48 in seven steps. Knoevenagel condensation of the aldehyde with Meldrum s acid, followed by in situ intramolecular hetero-Diels-Alder reaction afforded pyran 49, with all the carbons required for the natural product core installed. Conversion of 49a, via methanolysis and a reduction/elimination sequence, to lactol acetate 50, was achieved in four steps. Finally, glycosylation and deprotection provided the natural product in a total of 14 steps. 

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