Recent advances in the discovery and design of multicomponent reactions for the generation of small-molecule libraries

The current drug discovery process is dependent on the ability of synthetic chemistry to deliver libraries of small molecules with ever increasing levels of structural complexity and diversity. Sequencing multicomponent reactions (MCRs) with elaboration or cyclization steps represents an effective approach toward generating libraries of complex and diverse small molecules. This review highlights the most recent (2010–2015) examples of the application of reaction sequences including MCRs to the synthesis of diverse assemblies of small heterocycles. Sequences performed in multiple separate steps, or as one-pot operations, and including MCRs based on 1) carbonyl condensations; 2) isocyanide-based reactions; 3) cycloadditions; and 4) transition metal-mediated reactions are discussed.