This review provides a comprehensive overview on the preparation and synthetic applications of functionalized isocyanides.

This perspective aims at celebrating the 100th anniversary of the discovery of the Passerini three component reaction.

This account summarizes the results of studies carried out by the authors during the last 10 years aimed at expanding the utility of the venerable Passerini and Ugi reactions. Particular emphasis is given to efforts that focus on coupling these processes with post-condensation, intramolecular, aliphatic nucleophilic substitution and acyl nucleophilic substitution reactions. The methodologies developed in these investigations serve as the basis for short sequences for the preparation of a diverse number of interesting drug-like structures. 1 Introduction 2 Aliphatic Nucleophilic Substitution 2.1 Two Additional Functions: Mitsunobu or Mitsunobu-like Reactions 2.2 One Additional Function: Ketopiperazines, β-Lactams and More 2.3 One Additional Function: S_N2′ Reactions 3 Nucleophilic Acyl Substitutions: Acyl Migrations 3.1 Oxygen → Nitrogen Migration after Passerini (PADAM) 3.2 Nitrogen → Oxygen Migration after Ugi (UNOAM) 4 Nucleophilic Acyl Substitutions: Lactonization or Lactamization 4.1 Two Additional Functions 4.2 One Additional Function 5 Conclusions