Stefano Marcaccini: a pioneer in isocyanide chemistry.

Stefano Marcaccini was one of the pioneers in the use of isocyanide-based multicomponent reactions in organic synthesis. Throughout his career at the University of Florence he explored many different faces of isocyanide chemistry, especially those geared towards the synthesis of biologically relevant heterocycles. His work inspired many researchers who contributed to other important developments in the field of multicomponent reactions and created a school of synthetic chemists that continues today. In this manuscript we intend to review the articles on isocyanide multicomponent reactions published by Dr. Marcaccini and analyse their influence on the following works by other researchers. With this, we hope to highlight the immense contribution of Stefano Marcaccini to the development of isocyanide chemistry and modern organic synthesis as well as the influence of his research on future generations. We believe that this review will not only be a well-deserved tribute to the figure of Stefano Marcaccini, but will also serve as a useful inspiration for chemists working in this field.

The Castagnoli-Cushman Reaction.

Since the first reports of the reaction of imines and cyclic anhydrides by Castagnoli and Cushman, this procedure has been applied to the synthesis of a variety of lactams, some of them with important synthetic or biological interest. The scope of the reaction has been extended to the use of various Schiff bases and anhydrides as well as to different types of precursors for these reagents. In recent years, important advances have been made in understanding the mechanism of the reaction, which has historically been quite controversial. This has helped to develop reaction conditions that lead to pure diastereomers and even homochiral products. In addition, these mechanistic studies have also led to the development of new multicomponent versions of the Castagnoli-Cushman reaction that allow products with more diverse and complex molecular structures to be easily obtained.

Synthesis of imidazolocoumarins by the amide-directed oxidative cyclisation of enol-Ugi derivatives.

The oxidative C(sp3)-H intramolecular imination of hydroxycoumarin enol-Ugi adduct derivatives affords selectively diversely substituted imidazolocoumarins in one pot. The amide group derived from the enol-Ugi isocyanide component directs the functionalisation of the adjacent C(sp3)-H and then is lost as an isocyanate molecule in an unprecedented transformation. This strategy was applied for the synthesis of potential modulators of innate immune system receptor TLR7, which showed high binding affinities in the molecular docking studies.