Nitin D. Patil, Satish S. More
Reductive cyclization reactions occupies a versatile class of organic transformations for the construction of various cyclic and polycyclic molecular architectures from readily accessible acyclic precursors. Due to their ability to form carbon-carbon and carbon-heteroatom bonds in a single just operation, these reactions have become valuable tools for chemistry in synthetic chemistry, particularly for the preparation of heterocycles, carbocycles and structurally complex molecules. Significant developments in this area over the past decade have expanded the scope of reductive cyclization through advancement in reagent design, catalysis as well as reaction engineering. This review particularly summarizes representative developments in reductive cyclization chemistry with emphasis on methodologies based on samarium (II) iodide, low-valent titanium reagents, nitroarene-derived cyclizations, photoredox catalysis, electrochemical approaches, nickel-catalyzed processes and carbon dioxide-assisted transformations. Mechanistic aspects underlying radical, single-electron-transfer, and organometallic pathways are discussed to highlight common reactivity patterns and factors governing selectivity. The application of reductive cyclization reactions in the synthesis of biologically relevant molecules and natural-product-inspired frameworks is also examined through with selected examples. Recent trends toward catalytic, sustainable, and operationally simple protocols demonstrate the continuing progress of this field. The review concludes by outlining current challenges and emerging opportunities including asymmetric variants, electrocatalytic strategies, integrated catalytic systems and the use of renewable feedstocks. By providing an overview of recent progress, this article has aims to serve as a useful resource for researchers particularly interested in the development and application of reductive cyclization reactions in modern organic synthesis.