Knoevenagel Reactions in Multicomponent Syntheses

Multicomponent Reactions Concepts and Applications for Design and Synthesis, First Edition. Edited by Raquel R Herrera and Eugenia Marquds-L tez. 2015 John Wiley Sons, Inc. Published 2015 by John Wiley Sons, Inc. 

SCHEME 13.1 Proposed mechanism of the base-mediated Knoevenagel condensation. 

SCHEME 13.2 Proposed mechanism of the Knoevenagel condensation mediated by secondary amines 

Base-mediated 4//-pyran formation with nitrile-groups bearing CH-acids 

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H-pyrane] derivatives in the presence of isatins, malononitrile, and acetylacetone/ethyl 3-oxobutanoate [103]. Yan and coworkers showed in 2012 that chiral tertiary amine-thiourea (158) derived from quinine can catalyze a three-component reaction between isatins 118, malononitrile (119), and a-phenyl-isocyanoacetate (217) (Scheme 2.75) [104]. The process affords dihydropyrryl-spirooxindoles 218 and involves an initial Knoevenagel condensation of 118 and 119 followed by the nucleophilic anion attack of 217 (see the key transition state intermediate on Scheme 2.75). Final intramolecular cyclo-addition affords the expected compounds where H bond interactions are supposed to direct the attack of isocyanate anion and, consequently, contfol the enantioselectivity. One year later, Xu s group used a bifunctional cinchona-based squaramide to catalyze multicomponent cascade reaction to synthesize spiro[pyrrolidin-3,2 -oxindoles] via 1,3-proton shift and [3h-2]... 

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