Piperazine Scaffolds via Isocyanide-Based Multicomponent Reactions

Piperazine scaffolds are amongst the most extensively used backbones in medicinal chemistry and many bioactive compounds are built upon this template. The physicochemical properties and the three-dimensional structures of the different piperazine chemotypes are of utmost importance to understanding its biological activities. Knowing the synthetic access to this chemical space of piperazines is of great importance to designing compounds with better properties. Isocyanide-based multicomponent reactions (IMCRs) allow for the truly convergent and efficient access to not less than 35 different piperazine derived scaffolds. These are reviewed, and their scopes and limitations are discussed.