Michael/elimination cascade reactions

Synthesis of chiral heterocycles by domino organocatalytic processes has also been intensively studied. In particular, various benzo-fused heterocycles, such as chiral chromans, " thiochromanes, hydro-quinolines, dihydropyranes, or thiopyranes were investigated. These organocatalytic sequence were typically initiated by a hetero-Michael addition of a sulfur, oiqrgen or nitrogen nucleophile, which triggers the formation of an enolate/enamine that adds to the ortho electrophile terminating the cascade reaction. An elimination step or an additional cyclisation step follows (Scheme 8.25). 

The stoichiometric reaction of aromatic aldehydes with Meldrum s acid at 50°C gave an intermediate melt from which products 139 crystallized quantitatively at the reaction temperature (Scheme 2.47). These Knoevenagel condensations were termed melt reactions with direct crystallization. Similar condensation with dimedone 140 afforded a cascade reaction starting with Knoevenagel condensation, which was followed by elimination and subsequent Michael addition (Scheme 2.48). Unlike the solution synthesis, yields are superior and no wastes was produced. 

Cao et al. reported that enantioenriched bicyclic skeletons with four stereocenters could be obtained from Michael/elimination/Michael cascade reaction of cyclohexane derivatives 1 and ( )-2-nitroallylic acetates 227 with the promotion... 

Application of solid-state chemistry for quantitative multistep cascades in a ball mill is also demonstrated by reaction of enamine ketone 291 with 1,2-dibenzoylethene 292 (Scheme 3.78). Pyrrole derivative 293 was obtained by Kaupp et al. in quantitative yield through four reaction steps (vinylogous Michael addition, imine/enamine rearrangement, cyclization, and elimination), without the use of add catalysts [18]. 

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