Interrupted Ugi and Passerini Reactions: An Underexplored Treasure Island

Abstract

The formation of the key short-lived intermediate nitrilium ion in the Passerini and Ugi reactions was recognized early in the discovery of these two-multicomponent transformations. Surprisingly, the idea of intramolecularly intercepting it, eluding the attack by the carboxylate, and thus interrupting the normal course of the reaction, was missed by chemists for several decades. In this review we describe, in an exhaustive manner, the reported synthetic approaches, which can be categorized as interrupted Passerini/Ugi reactions. Besides, the clear goal of this review is to show the potential of these transformations, whilst highlighting the underexplored combinations of reagents toward the identification of novel interrupted Passerini/Ugi reactions.1 Introduction2 The Interrupted Ugi Reaction2.1 The Interrupting Functional Group is Present on the Amine Reactant2.2 The Interrupting Functional Group is Present on the Isocyanide Reactant2.3 The Interrupting Functional Group is Present on the Carbonyl Reactant3 The Interrupted Passerini Reaction3.1 The Interrupting Functional Group is Present on the Carbonyl Reactant3.2 The Interrupting Functional Group is Present on the Isocyanide Reactant4 Conclusions and Future Outlook

Selectivity in multiple multicomponent reactions: types and synthetic applications

“…The synthesis of aminomethyltetrazoles arising from two consecutive isocyanide-MCRs shows excellent selectivity and broad scope, and although it combines two different transformations, the amine component (ammonia in the starting mixture and a primary amino group in the first adduct) reacts at different rates in each substrate, allowing the controlled performance of both processes, leading to a formal two-step 6CR [45] (Scheme 11). Analogously, Ruijter reported an interrupted Ugi process [46] involving a 2-(3-indolyl)ethyl isocyanide, an aldehyde and an amine which elegantly led to the iminospiro adduct C (Scheme 11). This compound does not react under the initial reaction conditions, but can be forced to do so in a Joullié MCR with a new isocyanide/carboxylic acid pair [47].…”

Electrochemical TEMPO-Catalyzed Oxidative Ugi-Type Reaction

“…Inasmuch as they meet many of the criteria dictated by green chemistry, − this sustainable strategy has found many applications ranging from the production of fine chemicals to various uses in material sciences. ,− Isocyanide-based processes (IMCRs) have partaken substantially to the blossoming of this field. Since Passerini and Ugi demonstrated that the ambivalent reactivity of isocyanides could be successfully harnessed in multicomponent processes, , IMCRs have not ceased to bring stimulating developments. ,− ,− Nevertheless, one of the major impediments of IMCRs is that, because often relying on the use of Csp 2 O or Csp 2 N partners, such reactions largely rely on the use of carbonyl/imine derivatives, which may reveal themselves to be unstable enough to impede their preparation and, accordingly, their use.…”

Polymer Beads Decorated with Dendritic Systems as Supports for A3 Coupling Catalysts

“…Although, many multicomponent transformations are known more than hundred years (e.g. Mannich, Strecker, Ugi, Passerini and Petasis borono-Mannich reactions), the modern variants of the classic MCRs and also the new MCRs are still developed [10,12,[24][25][26][27][28][29]. A 3 coupling reactions, i.e.…”