Michael Addition cascade

The objective was to engineer a catalytic carbonylation-amination-Michael addition cascade employing carbon monoxide (1 atm). This cascade, if viable, could, conceptually, proceed via either of two pathways (Scheme 9). 

Scheme 27 Microwave-assisted Knoevenagel condensation and Michael addition cascade...

The mechanism of these MCRs involving Meldrum s acid should include Knoevenagel condensation and Michael addition cascade process [100, 113] (Scheme 37). To form positional isomeric reaction product, arylliden derivatives of Meldrum s acid are attacked by exocyclic NH2-group instead of endocyclic nucleophilic center. 

Palladium chemistry has been used in the synthesis of tetrahydroisoquinolines. Different combinations of iodoaryl-amine-alkene can be used in these multicomponent reactions. For example, the metal-mediated o-alkylated/alkenyl-ation and intramolecular aza-Michael reaction (Scheme 109) give moderate yields of heterocycle <2004TL6903>, whereas the palladium-catalyzed allene insertion-nucleophilic incorporation-Michael addition cascade (Equation 172) produces good yields of tetrahydroisoquinolines in 15 examples <2003TL7445> with further examples producing tetrahydroquinolines (Scheme 110) <2000TL7125>. 

Primary amines reacted via a palladium-catalysed allene insertion-nucleophilic incorporation-Michael addition cascade to give isoquinoline derivatives. The yields were good and fifteen examples are reported <03TL7445>. 

Bunce and coworkers explored the tandem SN2/Michael addition cascade of 6- and 7-halo-2-alkenoate esters using both primary amines and thiourea to form... 

Keywords Sulfonamides, vinyl ketones, toluene, DBU, room temperature, Michael addition, cascade reaction, cyclization, functionalized 3-aroyl-4-hydroxy-4-arylpiperidines, stereoselectivity... 

Wang, X.-R, An, J., Zhang, X.-X., Tan, R, Chen, J.-R., Xiao, W.-J. (2011). Catalytic asymmetric aza-Michael-Michael addition cascade enantioselective synthesis of poly-substituted 4-aminobenzopyrans. Organic Letters, 13, 808-811. 

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. 

Scheme 14.2 Imidazolinone-catalyzed hydride transfer/Michael addition cascade for the synthesis of (+)-ricciocarpin A.

Scheme 4.27 Synthesis of p-1,3-dicarbonyl aldehydes by a CDC-Michael addition cascade.

---