Six‐Component Reactions and Beyond: The Nuts and Bolts

Abstract

AbstractThe deployment of multicomponent reactions (MCRs), defined as containing three or more reactants, not only enjoys pot, atom, and step‐economy in the synthesis of novel complex molecules but also aligns with sustainable chemistry principles as a green symphony. Generally, more components lead to more complexity, and are taken to an extreme ‘‘higher‐order’’ MCRs, where six or even more components react in a one‐pot, have been developed, although they remain scarce compared to their 3, 4 and 5‐component relatives. On this topic, the rich footprint of isocyanides in MCRs has been fruitful in delivering higher order six to eight‐component reactions through mechanistically similar pathways. The present review encompasses a brief history of MCRs and their product utility, followed by a thorough discussion of the principles of reaction design that enabled the discovery of higher‐order MCRs, spanning 6 to 8‐components. Future challenges and opportunities will also be elaborated.