Electrooxidative Regiodivergent C–H Functionalization toward Six-Membered Azaheterocycles

Ghosh, Sayan (2026) Electrooxidative Regiodivergent C–H Functionalization toward Six-Membered Azaheterocycles. PhD thesis, Indian Institute of Science Education and Research Kolkata.

Text (PhD thesis of Sayan Ghosh (20RS139)) 20RS139.pdf - Submitted Version Restricted to Repository staff only Download (12MB)

Abstract

The thesis entitled “Electrooxidative Regiodivergent C–H Functionalization toward Six-Membered Azaheterocycles” showcases novel, eco-friendly electrochemical routes designed to construct various six-membered heterocyclic frameworks. The thesis is organized into six chapters, each delineating the experimental investigations carried out during the course of the doctoral research, with the first chapter devoted to an introduction to electrochemistry and the chemistry of six-membered heterocycles. Six-membered heterocycles occupy a central position in contemporary science and industry owing to their rich chemical versatility and broad spectrum of biological activities, thereby continually inspiring the development of efficient and sustainable synthetic methodologies. In this context, there has been a growing shift toward environmentally benign approaches, with organic electrosynthesis emerging as a powerful alternative to conventional reagent-based redox transformations. Electrochemical strategies offer unique advantages, including precise control over reaction pathways through modulation of parameters such as applied potential, which enhances selectivity and efficiency while suppressing undesired side reactions. Within this framework, the present doctoral work focuses on the electro-oxidative synthesis of strategically functionalized six-membered heterocyclic scaffolds, proceeding via radical addition followed by polar cascade cyclization or through radical annulation followed by polar addition processes occurring at the electrode surface. Introductory Chapter 1 presents an overview of the significance of heterocyclic compounds along with the fundamental principles of organic electrochemistry. In Chapter 2, the synthesis of lactone- or lactam-fused quinoline frameworks is described via an electrochemical intramolecular [4+2] annulation strategy. Cyclic voltammetric studies, together with systematic control experiments, indicate an electrocatalytic process involving the consecutive formation of C–C bonds. Chapter 3 focuses on the development of an environmentally benign electro-oxidative hydrogen atom transfer (HAT) catalyzed methodology for the synthesis of multisubstituted quinolines using alanine- and glycine-based amino acid derivatives. Mechanistic investigations support an enamine–imine cross-coupling pathway that culminates in ring construction through a formal (5+1) annulation. In Chapter 4, an electrocatalytic strategy enabling remote activation of amino acid derivatives is disclosed. This regiodivergent approach establishes a chemoselective pathway for the construction of [4+2] annulated quinoline frameworks. In Chapter 5, a sequential electro–photocatalytic strategy is introduced for the efficient synthesis of highly functionalized quinoline architectures. The methodology features electrochemical generation of a stable imine intermediate, followed by a photochemically driven transformation to afford the desired quinoline framework. In Chapter 6, a green electro-oxidative method for the regioselective ring opening of imidazopyridine frameworks is presented. The protocol proceeds under mild conditions and provides streamlined access to N-(pyridin-2-yl)amide derivatives, with DMSO acting as the oxygen source.

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