Multicomponent Coupling Reactions for Organic Synthesis: Chemoselective Reactions with Amide–Aldehyde Mixtures

Abstract

The acid-catalyzed condensation chemistry of simple amides and aldehydes provides a highly prolific source of diverse reactants for irreversible follow-up reactions. Amide-aldehyde mixtures have been successfully employed in multicomponent syntheses of N-acyl alpha-amino acids (via palladium-catalyzed amidocarbonylation) and various cyclohexene, cyclohexadiene, and benzene derivatives (via the amide-aldehyde-dienophile (AAD) reaction).

An efficient protocol for the synthesis of N-fused 2, 5-diketopiperazine via base catalyzed Ugi-type MCR

“…Ugi type reaction is not only used for biological screening in medicinal chemistry but also used for synthesis of drug molecule or drug intermediate as well. 6 The post functionalization of MCR [7][8][9][10][11] adducts has received considerable attention in recent years. Because of its combination with various post-transformations, typically cyclization, provides a fast and efficient entry to libraries of diverse heterocyclic scaffolds.…”

Asymmetric Multicomponent Reactions (AMCRs): The New Frontier

“…Several reviews on different aspects [17] and reaction types, such as Biginelli, [18] isocyanide-, [19] palladium-, [20] organometallic-, [21] and amidocarbonylation-based [22] multicomponent reactions have already been published. However, the asymmetric aspect of this methodology has not yet been discussed, and with this Review we would like to fill this gap.…”

Second Generation Protocol for Multicomponent Coupling Reactions of Aldehydes, Amides and Dienophiles

“…Based on the history of the discovery of the AAD-MCR, [15] so far all successful reactions were carried out in dipolar aprotic solvents, typically NMP. Despite the general applicability of these conditions, sometimes purification of the desired product is troublesome.…”