Owing to the countless plausible combinations of carbon, hydrogen, and various heteroatoms, heterocyclic chemistry has remained as the foundation of novel chemical compounds in the sphere of natural product chemistry, pharmaceuticals, agrochemicals, and material sciences. They can serve as useful tools to facilitate tunable interactions with biological targets, thereby providing improved pharmacological and physicochemical properties of biomolecules as well as drug candidates. Recently, heightened cognizance of environmental issues is directing our society toward more sustainable solutions. Ever since the 12 principles of Green Chemistry were articulated, chemists answered the call to play their part in generating more sustainable syntheses. Multicomponent reactions (MCRs) appear as an obvious solution since most of the reactants' atoms are often incorporated in the final product. Moreover, a vast literature has been produced showing the power of MCRs as well as post-MCRs, in simplifying the synthetic design and yet obtaining high complexity and diversity in the construction of privileged structures. This is crucial in the development of novel bioactive molecules, wherein the production of libraries of compounds is necessary for the search of optimal drug candidates. Given the broad applications of heterocycles in the plethora of scientific fields, the current book title “Multicomponent Reactions towards Heterocycles. Concepts and Applications” is well warranted. In addition, recent advances in the field of MCR chemistry along with the plausible scope toward the synthesis and functionalization of biologically relevant heterocycles has encouraged us to compile this volume.

As the vast majority of small molecule drugs are of heterocyclic nature, the interplay of heterocycles with MCRs becomes therefore significant. The first chapter focuses on the recent progress made in the area according to the main reactivity mode involved in the transformation: concerted, radical, metal-catalyzed, carbonyl/imine, and isocyanide-based processes. The chapter itself provides an overview of heterocycles as input in MCRs. The next chapter “Heterocycles and Multi-Component Polymerizations” highlights some of the latest examples in this emerging field. The third chapter highlights examples from the viewpoint of target-oriented synthesis, the use of MCR in medicinal chemistry, from drug discovery, synthesis of drugs, to screening libraries, and biopharmaceutical applications. Further, heterocyclic chemistry has traditionally relied on solution-phase synthesis as technological platform to discover and produce bioactive scaffolds. The next chapter “Solid-phase Heterocycle Synthesis using Multicomponent Reactions” highlights methodological aspects of the implementation of on-resin MCRs to produce heterocycle compounds. Different name reactions, synthetic strategies, and solid-supports are analyzed critically in this chapter.

In the synthesis of heterocyclic compounds, MCRs have inherent advantage on pot, atom, and step economy (PASE) and are simple in operation, consume less energy, and release a reduced amount of waste. The fifth chapter discusses MCR-based green synthetic methods, including high-order MCRs, consecutive MCRs, MCRs followed by cyclization, and cycloaddition reactions, for the synthesis of heterocycles. Further, the use of enabling methods viz. continuous flow approaches has been beneficial in terms of yield, selectivity, reaction time, real-time monitoring. The next chapter is focused on different methodologies that can be used to perform heterocycle multicomponent syntheses in a continuous flow, to highlight the advantages over batch synthesis. Similarly, the next chapter analyzes a merging of C–H functionalization and MCRs approaches toward synthesis and modification of heterocyclic compounds.

MCRs have demonstrated their reliability and effectiveness as a synthetic approach that provides rapid access to chemical complexity. Among the many factors that bring this about, the MCR effect stands out, based on the fact that a changed number of reagents becomes the main differentiating factor of the reaction direction, that enables multicomponent-switched heterocyclizationsasymmetric MCRs

Finally, we are extremely grateful to all authors for their excellent contributions to this volume. We are also thankful to the Wiley editors in particular Dr. Elke Maase and Ms. Katherine Wong for their professional support and assistance during this endeavor.