A Mimicry of Primary Amines by Bis‐Secondary Diamines as Components in the Ugi Four‐Component Reaction

Abstract

Splitting the amine! The Ugi four‐component reaction (Ugi 4CR) relies on the presence of a component with a primary amino group. This protocol has been modified by “splitting” the primary amine into two secondary amines. The resulting variant of the Ugi 4CR proceeds with good to excellent yield and widens the versatility of the original multicomponent reaction by enabling variation of the molecular backbone.

DEAD‐Promoted Oxidative Ugi‐Type Reaction Including an Unprecedented Ugi Amidation Assisted by Dicarboxylic Acids

“…Based on the above mechanism, our method could be considered to be a representative Ugi‐MCR, concisely providing α‐amino amides without using water as a nucleophile , . Unlike typical Ugi amidation reactions, which use endogenous water generated during the imine or iminium ion formation,[3g], [3h], , the amide carbonyl oxygen atom in this protocol is introduced through an intramolecular nucleophilic attack on the imino anhydride intermediate (Scheme ) . The dicarboxylic acids act as readily accessible and highly reactive alternatives to water for the insertion of the amide carbonyl oxygen atom, especially when added water could not facilitate the amide formation (Table , Entry 9).…”

A One-Pot Synthesis of Oxazepine-Quinazolinone bis-Heterocyclic Scaffolds via Isocyanide-Based Three-Component Reactions

“…Combination of a molecule with several heterocyclic compounds with different pharmacological activities due to the synergism effect is a useful strategy to assign and discover new biological compounds. The Ugi four-component reaction (U-4CR) is one of the most commonly used multicomponent reactions (MCRs), in which a carboxylic acid, an amine, a carbonyl compound, and an isocyanide are reacting to result in peptide-like heterocyclic products (Hebach and Kazmaier, 2003; Dömling, 2006; Giovenzana et al, 2006; Ngouansavanh and Zhu, 2007; Hartweg and Becer, 2016; Yugandhar et al, 2016). Although a large diversity can be quickly achieved through the U-4CR, the scaffolds that are accessible through it are limited.…”

Interrupted Ugi and Passerini Reactions: An Underexplored Treasure Island

“…30 Although, also in this case, only one example was reported, it would be reasonable to think that the reaction is general. Of note, when a carboxylic acid is present, the split Ugi 5 reaction wins over this interrupted Ugi reaction.…”

“…3 Sometimes, by chance or by rational thinking, some gems were brought to light allowing for the construction of complex molecular frameworks in one or two synthetic steps. In brief, the use of nitrophenols, 4 symmetrical secondary diamines, 5 isocyanoacetamides, 6 to cite but a few, have shown how these transformations can take a different pathway at a precise point of the Ugi and Passerini reaction mechanism. The classical ionic mechanism for both the Passerini and the Ugi reaction considers the formation of the nitrilium ion, generated by the reaction between an electrophile and an isocyanide, being the key point for the success of these transformations.…”