Iminium-Activated Multicomponent Reactions

SCHEME 1.72 Thiol addition-amination-reduction-cyclization reaction. 

Quintard and Alexakis developed a double Michael addition reaction of enals, taking advantage of the high reactivity of vinyl sulfone-initiated nucleophilic addition of benzaldoxime, triazole, Angelica lactone, benzyl mercaptan, and 174. The powerful organocascade allows for the rapid construction of highly attractive synthons in high enantioselectivities (typically, 99% ee) [117]. 

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Iminium-activated aziridinations Iminium-aetivated multicomponent reactions Iminium-activated [3-1-3] reactions... 

The first multicomponent reaction initiated by a Michael addition combining enamine and iminium ion activations was reported by j0rgensen et al., in 2005... 

Combinations of enamine-iminium ion activations together with other organo-catalytic activations in asymmetric organocatalytic domino and multicomponent reactions have been developed to achieve the enantioselective consecutive formation of two or more bonds in a stereoselective fashion. 

Enamine-Iminium-Enamine Cascades The enamine-activated process followed by an mtermolecular iminium-mediated process will undergo a new enamine activation step to afford multisubstituted cyclohexanes via an enantine-intinium-enantine sequence. In this way, multicomponent reaction could be designed to produce complex structures from simple reactants. 

As illustrated in Scheme 1.40, in addition to the amphiphilic reactants bearing nucleophilic and electrophilic sites, compatible separated nucleophiles and electrophiles can also be employed in iminium-activated cascades in multicomponent reactions. 

Karami and coworkers reported multicomponent, solvent-free reactions for the synthesis of benzofurans (Scheme 11.20) [67]. The reaction of arylglyoxals 108 with benzamide derivatives 109 afforded the corresponding iminium intermediate that after the nucleophilic attack by phenol derivatives 110 and intramolecular cyclization gave the corresponding benzofurans 111 in good yields (75-85%). The reaction was efficiently catalyzed by tungstate sulfuric add (TSA) that after the reaction could be isolated and reused without loss of its catalytic activity. 

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