Calcium-Catalyzed Multicomponent Reactions in Organic Synthesis

Calcium catalysis has garnered significant attention from synthetic organic chemists as a sustainable alternative to Lewis acidic transition metals, rare-earth metals, and strong Brønsted acids. This alkaline earth metal, abundant in nature, environmentally benign, moisture-tolerant, biodegradable, and low in toxicity, offers distinct advantages. Calcium catalysts exhibit exceptional proficiency in activating diverse functional groups, particularly π-activated species such as ketones, alcohols, enamines, aldehydes, alkenes, alkynes, and allenes, thereby enabling nucleophilic additions and tandem chemical transformations. These characteristics resonate with the core tenets of green chemistry, enhancing atom and step economy while minimizing waste generation. This review presents a thorough and in-depth analysis of calcium-catalyzed multi-component reactions (MCRs), underscoring their transformative role in advancing sustainable organic synthesis. Furthermore, it explores the untapped potential of calcium catalysis in broadening the horizons of MCRs, and fostering innovative and eco-friendly methodologies for applications in pharmaceuticals and materials science. Key challenges and future prospects within this evolving domain are also critically examined.