Expanding Chemical Space using Photo(redox) Catalysis

Jana, Sayan Kumar (2025) Expanding Chemical Space using Photo(redox) Catalysis. PhD thesis, Indian Institute of Science Education and Research Kolkata.

Text (Phd thesis of Sayan Kumar Jana (18IP012)) 18IP012.pdf - Submitted Version Restricted to Repository staff only Download (67MB)

Abstract

Photocatalytic technologies have demonstrated significant potential in recent years for addressing environmental pollution and energy shortages. A key advantage of visible-light-driven photocatalysis is its efficient utilization of the vast energy from solar radiation, serving as a clean, cost-effective, and renewable energy source. A breakthrough in this field was the discovery that simple metal complexes and organic dyes can turn visible light into chemical energy under very mild conditions, depending upon their redox potential and triplet energies. Single electron transfer (SET) and energy transfer (EnT) are the two main pathways in visible light photocatalysis. Chapter-1. A roadmap towards photocatalysed electron transfer and energy transfer This chapter includes a general introduction to photocatalyzed single-electron transfer and energy transfer. The photocatalyzed SET process is utilised in the generation of a low-valent nickel complex, which is discussed here. This nickel catalysis is subsequently used for the synthesis of several C-C bonds via cross electrophile coupling. In the other part dearomative photocycloaddition is discussed using photocatalyzed energy transfer process. Arene, from a topological point of view, consists of both diene and dienophile. Here different mode of cycloaddition like [2π + 2σ], [2π + 2π], [2π + 4π] cycloadditions are discussed. Chapter-2. Photoredox/Nickel Dual Catalysis Enables the Synthesis of Alkyl Cyclopropanes via C(sp³)-C(sp³) Cross Electrophile Coupling of Unactivated Alkyl Electrophiles A facile synthesis of mono-, 1,1- and 1,2-disubstituted cyclopropanes via visible light-mediated photoredox/nickel dual catalysis is demonstrated. The challenging intramolecular C(sp³)-C(sp³) cross-electrophile coupling of readily available unactivated 1,3-dialkyl electrophiles were performed under mild conditions that allowed traditionally reactive functional groups to be included. Mechanistic inspection and control experiments revealed the importance of dual catalysis and that the reaction proceeds via a stepwise oxidative addition followed by an intramolecular SN2 reaction. Chapter-3. Photoredox/Nickel Dual Catalysis for C(sp²)-C(sp³) Cross Electrophile Coupling Reaction of Mesylates of Phenols and Primary Alcohols Introducing alkyl groups, particularly through innovative C(sp²)-C(sp³) bond-forming methods utilizing abundant feedstocks, holds promise for expanding chemical diversity, especially in drug discovery programs. Herein, we employed biomass-derived abundant phenols and unactivated aliphatic alcohols as the coupling partners for the C(sp²)-C(sp³) cross-electrophile coupling reactions. Our innovation involved activating both the coupling partner via the same activator and designing a catalytic system that activates stronger bonds while ensuring cross-selectivity. The visible-light photoredox/nickel dual catalytic systems accommodate a large substrate scope, tolerating diverse functional groups. Besides, both the activation and cross-coupling reaction could be performed in one pot, and the reaction could be scaled up. The method was also executed for iterative cross-coupling and applied for the late-stage functionalization of drug molecules, highlighting synthetic applicability. Preliminary mechanistic studies involving luminescence quenching, cyclic voltammetry, radical quenching, and radical clock studies elucidated the proposed reaction mechanism. Chapter-4. Substrate Driven Regiospecific Dearomative [2π + 2σ] Photocycloaddition of Polyfluoro-naphthalenes with Bicyclo[1.1.0]butanes Enabled by Visible Light Energy Transfer Catalysis Herein, we report a regiospecific dearomative [2π+2σ] cycloaddition of bicyclo[1.1.0]butanes (BCBs) with polyfluoronaphthalenes enabled by visible light-driven energy transfer (VLEnT) catalysis. This transformative approach addresses the longstanding challenge of functionalizing inert polyfluorinated aromatics while providing unprecedented control over reactivity and selectivity. The mild reaction conditions accommodate diverse mono- and di-substituted BCBs, delivering structurally complex, fluorinated C(sp³)-enriched scaffolds in excellent yields (up to 96%) with exceptional regioselectivity (>20:1 rr). Demonstrating practical utility, the protocol is readily scalable under both batch and continuous flow conditions. Furthermore, a sequential VLEnT cascade unlocks access to architecturally diverse polycyclic frameworks that are inaccessible through conventional methods. This work significantly expands the synthetic toolbox for fluorinated arene diversification, with potential applications in pharmaceutical, agrochemical, and advanced materials development. Chapter-5. Substrate Controlled Regiospecific Dearomative [2+2] and [4+2] Cycloaddition of Polyfluoronaphthalene via Visible Light Mediated Energy Transfer Catalysis Controlling various aspects of reaction selectivity, including stereoselectivity and regioselectivity, has long been a complex and enduring challenge in the field of synthetic organic chemistry. Based on the orbital symmetry and mode of connection, the arene–arenophile cycloaddition can be of three types: ortho [2+2], meta [3+2], and para [4+2]. Herein, we have reported a double dearomatisation in polyfluoroarene for the first time. We have established a substrate control dearomatisation protocol that switches the cycloaddition mode depending upon the olefin substitution. A broad range of cycloaddition reactions was performed. Mechanistic studies prove the cycloaddition reaction is completely governed by photosensitised energy transfer.

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