Multicomponent reactions and radical chemistry

Multicomponent reactions (MCRs) have a long history, dating back to the beginning of the last century with the advent of the Mannich reaction. Other remarkable developments, such as Robinson's 3-component synthesis of tropinone, are also worth mentioning in this context. More recently, the 4-component reactions of Ugi and Passerini have attracted particular attention, providing access to large libraries of molecules. However, it is process automation and parallel synthesis that have led to the most significant developments in multicomponent reactions over the last twenty years. The pharmaceutical industry has played a leading role in this respect, with the preparation of thousands of new molecules combined with high-throughput screening opening up new prospects in the quest for new therapeutic agents. A growing number of new transformations are now based on the so-called "multicomponent" strategy, giving access to new molecular architectures. CMR symbolizes a form of "Grail" for the organic chemist, being considered the optimal process in terms of convergent synthesis, perfectly in phase with the concepts of economy of steps and atoms, keystones of so-called "green" chemistry. While many multicomponent reactions are based on ionic and/or organometallic processes, few involve radical reactions. This chapter is intended to bring together, albeit not exhaustively, the various multicomponent reactions based on free-radical processes, and making use of environmentally-friendly processes. In particular, we will describe the various methods for assembling three, four or even more fragments in so-called "one-pot" processes, using radical transformations or combining radical and ionic processes, or radical and organometallic processes. Particular attention will be paid to "tin-free" processes, a field in constant evolution due to the proven toxicity of carbon derivatives of tin.