1,4-Addition Ugi Reaction Using Cyclic α,β-Unsaturated Ketone as Substrate

Abstract

A four-component, 1,4-addition Ugi reaction using cyclic α,β-unsaturated ketones, carboxylic acids, amines, and isocyanides was developed for the first time. By combining this reaction with Michael addition, nucleophilic substitution, and C-N bond formation reactions, bicyclic and tricyclic scaffolds with pyridinone and quinolinone moieties, two basic units among a variety of natural products and pharmaceuticals, were constructed.

Sustainable Synthesis of Pseudopeptides via Isocyanide-Based Multicomponent Reactions in Water

“…In the next step, a carboxylate ion attacked 9 to enamine 50 to afford intermediate 51 , which rearranged through an intramolecular cyclization to generate imine 52 . Finally, imine-enamine tautomerization was performed to produce the desired product 47 …”

“…60 In an interesting work, Lu and coauthors introduced a novel 1,4-addition Ugi reaction among cyclic α,β-unsaturated ketone 46, amine 5, carboxylic acid 2, and isocyanide 1 in water/methanol conditions at 60 °C, which leads to pharmaceutical interesting scaffolds 47 (Scheme 13). 61 When substituted cyclopent-2-en-1-ones were used as ketones, the products were in the form of diastereoisomers pairs, some of which were easily separated by column chromatography. Remarkably, when secondary amines such as pyrrolidine and piperidine were used in the reaction, the desired products were obtained with moderate yields.…”

“…Finally, imineenamine tautomerization was performed to produce the desired product 47. 61 Enzymes are proteins that are widely used today as biocatalysts or natural catalysts in organic chemical transitions. 62 In 2019, Oszelewski and co-workers introduced a novel Ugi-type reaction based on the isocyanoesters in the presence of an enzyme as a biocatalyst.…”

One-Pot Metal-Free Synthesis of [1,2,3]triazolo[1,5-a]-quinoxalines by Sequential Ugi-3CR/Alkyne-Azide Cycloaddition Reaction

“…[8] The catalytic three-component Ugi reaction (Ugi-3CR) affords an α-amino amide by using aldehyde, primary amine and isocyanide in the presence of the catalyst such as acid, bromodimethyl-sulfonium bromide or ZnO-NPS and so on. [9] In addition, some new progress of Ugi reaction like 1,4-additon Ugi reaction [10] and chiral phosphoric acid catalyzed asymmetric Ugi reaction [11] have further promoted the development of Ugi reaction. However, the most of Ugi products construct linear peptide adducts rather than heterocyclic rings, the so-called post-Ugi modifications have been emerged as powerful approaches to access heterocyclic compounds.…”

One-Pot Synthesis of [1,2,3]Triazolo[1,5-a]quinoxalin-4(5H)-ones by a Metal-Free Sequential Ugi-4CR/Alkyne–Azide Cycloaddition Reaction

“…2 Among the IMCRs family, the four-component Ugi reaction (Ugi-4CR) is considered as one of the best-known IMCRs, because of its efficiency, diversity, and unexplored chemical space. 3 Moreover, some new progress of Ugi reactions such as 1,4-additon Ugi reaction 4 and chiral phosphoric acid catalyzed asymmetric Ugi reaction 5 further have promoted the development of IM-CRs. However, the classical Ugi-4CR gives rise to linear peptide adducts rather than a heterocyclic ring by using fourcomponents of amine, aldehyde, acid, and isocyanide in a one-pot fashion.…”