Multicomponent Reaction Design in the Quest for Molecular Complexity and Diversity

Multicomponent reactions have become increasingly popular as tools for the rapid generation of small‐molecule libraries. However, to ensure sufficient molecular diversity and complexity, there is a continuous need for novel reactions. Although serendipity has always played an important role in the discovery of novel (multicomponent) reactions, rational design strategies have become much more important over the past decade. In this Review, we present an overview of general strategies that allow the design of novel multicomponent reactions. The challenges and opportunities for the future will be discussed. MCRs à la carte: Multicomponent reactions have become essential tools for the rapid generation of molecular complexity and diversity in chemical biology and drug discovery. These reactions are often discovered by serendipity, but rational design strategies are now playing an increasing role. Several such strategies are discussed in this Review.