Tetravalent Silicon Lewis Acid (TMSOTf)-Enabled Annulative Construction of Nitrogen Heterocycles

Tetravalent silicon Lewis acid (TMSOTf) have emerged as a potent and versatile catalyst in modern organic synthesis. TMSOTf offered a green and atom economical approach for the construction of a wide range of N-heterocyclic frameworks, including indoles, imidazoles, indazoles, quinolines, pyridine, piperidine, pyrrolidone, maleimides, and many more; which are key structural motifs in pharmaceuticals, agrochemicals, and functional materials. It is compatible with various nucleophilic partners and solvents and has reduced by-product formation. This makes an attractive alternative to traditional metal-based Lewis acids. Recent advancements have demonstrated TMSOTf-mediated multi-component reactions, cascade cyclizations, and tandem transformations that afford complex N-heterocycles in high yields with excellent regioselectivity and stereoselectivity. Its key features, such as simple operation, tolerance toward moisture under optimized conditions, and recyclability, has enhanced its synthetic utility. This review included all the protocols including synthesis of nitrogen heterocyclic molecules using TMSOTf from 2019 to 2025 with reaction conditions, substrate scope, mechanism, and their applications. Overall, TMSOTf-catalyzed heterocyclic synthesis represented a metal free approach for the diverse nitrogen heteroaromatic and saturated ring systems. This reinforced the role of silicon-based Lewis acids in contemporary organic chemistry.