As valuable C1 building blocks, isocyanides represent an important class of reactive species and synthons. During the past decades, exhaustive efforts have been devoted to the discovery of highly efficient reactions involving isocyanide on the basis of the development of the Passerini and Ugi reactions. Several types of reactions involving isocyanides have been reported, such as nucleophilic attack, electrophilic addition, imidoylation reactions, and oxidation etc. In this review, recent progress in isocyanide insertion chemistry is presented. Among all isocyanide insertions, two catalytic systems have been developed, that is, Lewis (Bronsted) acid-catalyzed isocyanide insertions and transition-metal-enabled isocyanide insertions, respectively. This review is hence written in the sequence of Lewis (Bronsted) acid-catalyzed isocyanide insertion and transitional metal-enabled isocyanide insertion, where isocyanide insertion into heteroatom–hydrogen bonds, carbon–halogen bonds, carbon–hydrogen bonds, and metal carbenes are summarized.

Recent advances in isocyanide insertion chemistry

Metal-mediated and metal-catalyzed reactions of isocyanides.

Isocyanides have been important building blocks in organic synthesis since the discovery of the Ugi reaction and related isocyanide-based multicomponent reactions. In the past decade isocyanides have found a new application as versatile C1 building blocks in palladium catalysis. Palladium-catalyzed reactions involving isocyanide insertion offer a vast potential for the synthesis of nitrogen-containing fine chemicals. This Minireview discusses all the achievements in this emerging field.

Palladium-catalyzed migratory insertion of isocyanides: an emerging platform in cross-coupling chemistry.

Formal [4+1] Annulation Reactions in the Synthesis of Carbocyclic and Heterocyclic Systems

Isocyanides possess a rich history in the world of synthetic chemistry. Recently the scope of this already versatile class of reagent has been expanded into its use in palladium-catalysed cascade sequences. The scope of this type of reaction is explored in depth and this tutorial review focuses on its various applications in chemical synthesis, and the wide range of systems that can be efficiently prepared using this strategy are documented.

Unravelling the labyrinth of palladium-catalysed reactions involving isocyanides

O(2) in, H(2)O out: Various diamines and related bisnucleophiles readily undergo oxidative isocyanide insertion with Pd(OAc)(2) (1 mol %) as the catalyst and O(2) as the terminal oxidant to give a diverse array of medicinally relevant N heterocycles. The utility of this highly sustainable method is demonstrated by a formal synthesis of the antihistamines astemizole and norastemizole.

Sustainable Synthesis of Diverse Privileged Heterocycles by Palladium‐Catalyzed Aerobic Oxidative Isocyanide Insertion

The synthetic strategies towards thiosulfonates (RSO2SR1) are comprehensively reviewed from their original discovery to recent advances. Incorporation of the green credentials of the synthetic procedures towards thiosulfonates allows one to judge the merits of the state of the art, beyond the typical yield of a product and availability of the reactants. As reactant for organic transformations, thiosulfonates are particularly interesting given their possibility to react with nucleophiles, electrophiles and radicals. This review aims to give researchers, not familiar with the field, a good understanding of the general applications of thiosulfonates, while not skipping the recent important advances. The related, but less explored, selenosulfonates (RSO2SeR1) are also covered. (Figure presented.).

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Thiosulfonates as Emerging Reactants : Synthesis and Applications

Multiple applications of isothioureas as fine chemicals (or their precursors) are known, but a general sustainable method for their synthesis was hitherto unavailable We report a novel general approach towards S-alkyl and S-aryl isothioureas through a copper(I)-catalyzed three-component reaction between amines, isocyanides, and thiosulfonates The formal synthesis of a superpotent sweetener further illustrates the applicability of our method

Pieter Mampuys

Papers

Sustainable Synthesis of Diverse Privileged Heterocycles by Palladium‐Catalyzed Aerobic Oxidative Isocyanide Insertion

Thiosulfonates as Emerging Reactants : Synthesis and Applications

Sustainable Three‐Component Synthesis of Isothioureas from Isocyanides, Thiosulfonates, and Amines

Iodide-Catalyzed Synthesis of Secondary Thiocarbamates from Isocyanides and Thiosulfonates

An evaluation of credentials of a multicomponent reaction for the synthesis of isothioureas through the use of a holistic CHEM21 green metrics toolkit