Michael/elimination cascade

Scheme 7.78 Enantioselective synthesis of 4-alkylidene glutamic acids by cascade Michael/elimination process.

Qin, H., Xu, Z., Cui, Y, Jia, Y. (2011). Total Synthesis Of ( )-Decursivine And ( )-Serotobenine a witkop photocyclization/elimination/O-Michael addition cascade approach. Angewandte Chemie International Edition, 50, 4447-4449. 

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... 

The solid-state interaction of enamines (428, 333a) with trans-l,2-diben-zoylethene (87) provides quantitative yields of the pyrrole derivatives 445 or 446 [140]. These remarkable 5-cascades consist of initial vinylogous Michael addition, enol/keto tautomerism, imine/enamine tautomerism, cyclization, and elimination, all within the crystal without melting. A waste-free extraordinary atom economy is achieved that cannot nearly be obtained in solution. The milling times are unusually long here (3 h) but it s certainly worth the effort... 

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. 

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]. 

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). 

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