Exploiting the acylating nature of the imide-Ugi intermediate: a straightforward synthesis of tetrahydro-1,4-benzodiazepin-2-ones.

We describe a simple and novel protocol for the synthesis of tetrahydro-1,4-benzodiazepin-2-ones with three points of diversity, exploiting the acylating properties of the recently rediscovered Ugi-imide. The final compounds can be easily prepared in three synthetic steps using a multicomponent reaction, a Staudinger reduction, and an acylative protocol, with good to excellent yields for each synthetic step.

A novel α-isocyanoacetamide-based three-component reaction for the synthesis of dialkyl 2-acyl-5-aminofuran-3,4-dicarboxylates.

α-Isocyanoacetamides, acyl chlorides and dialkylacetylenedicarboxylates undergo a smooth multicomponent reaction to produce dialkyl 2-acyl-5-aminofuran-3,4-dicarboxylates in good yield. The scope and mechanism of this new multicomponent transformation are discussed.

Synthesis, molecular docking and biological evaluation as HDAC inhibitors of cyclopeptide mimetics by a tandem three-component reaction and intramolecular [3+2] cycloaddition.

Novel macrocyclic peptide mimetics have been synthesized by exploiting a three-component reaction and an azide-alkyne [3 + 2] cycloaddition. The prepared compounds were screened as HDAC inhibitors allowing us to identify a new compound with promising biological activity. In order to rationalize the biological results, computational studies have also been performed.

Synthesis of Passerini-Ugi hybrids by a four-component reaction using the glycolaldehyde dimer.

Passerini-Ugi hybrid adducts can be obtained through a four-component reaction by using glycolaldehyde dimer.

An efficient synthesis of symmetric and unsymmetric bis-(ß-aminoamides) via Ugi multicomponent reaction.

A library of symmetrical and unsymmetrical bis-(ß-aminoamides) has been prepared starting from symmetrical secondary diamines by using a double Ugi four-component reaction. A sacrifical Mumm rearrangement, thanks to the use of 2-hydroxymethyl benzoic acid, is necessary to suppress the competing split-Ugi reaction, increasing the yield and simplifying the purification step. The scope, the reaction conditions, and the role of water in trapping the nitrilium intermediate are also discussed.

Imides: forgotten players in the Ugi reaction. One-pot multicomponent synthesis of quinazolinones.

Up to now, the synthesis of quinazolinones has required lengthy synthetic procedures. Here, we describe an innovative one-pot multicomponent reaction leading to highly substituted quinazolinones. We believe that this novel transformation may open the door for the generation of new and pharmacologically active quinazolinones, but, most important of all, the resurrection of the imide-Ugi scaffold paves the way for the synthesis of novel molecular architectures.

Stereospecific synthesis of syn-α-oximinoamides by a three-component reaction of isocyanides, syn-chlorooximes, and carboxylic acids.

A stereospecific multicomponent reaction among isocyanides, syn-chlorooximes, and carboxylic acids provides an efficient synthesis of biologically relevant syn-α-oximinoamides.

Efficient synthesis of alpha-ketoamides via 2-acyl-5-aminooxazoles by reacting acyl chlorides and alpha-isocyanoacetamides.

Acyl chlorides and alpha-isocyanoacetamides undergo an efficient reaction in dichloromethane in the presence of triethylamine to give 2-acyl-5-aminooxazoles. Subsequent acid hydrolysis of the 5-aminooxazole moiety leads to alpha-ketoamides in good overall yields.