Design and Development of Regioselective Carbon–Carbon Bond Formation via Excited Transition Metal Catalysis under Visible Light

The construction of carbon–carbon (C–C) bonds with high regioselectivity remains a central goal in organic synthesis due to its pivotal role in assembling complex molecular architectures. Recent advances in photoredox catalysis have revolutionized synthetic strategies by enabling the generation of reactive intermediates under mild and environmentally benign conditions. This thesis explores the design and development of regioselective C–C bond-forming methodologies mediated by visible-light photoredox catalysis in complex molecular architectures such as carbohydrates and simple molecular structures such as styrenes, with a focus on both mechanistic understanding and synthetic applications.

By leveraging unconventional photocatalytic systems—specifically palladium- and copper-based photocatalysts—we explore radical pathways that enable precise site-selective functionalizations. Central to this work are: (i) excited-state palladium-catalyzed selective transformations at the C1-position of sugars, (ii) excited-state palladium-catalyzed functionalizations at the C2-position of sugars, and (iii) excited-state copper-catalyzed α-carbo-β-oxo difunctionalization of styrenes. Regioselectivity is finely controlled through deliberate substrate engineering and careful modulation of reaction conditions, with unique acyloxy migration mechanisms playing a pivotal role in the latter two transformations. These methodologies further facilitate late-stage diversification of structurally complex scaffolds, broadening the scope of tools available for medicinal chemistry and molecular editing. Mechanistic investigations, via radical clock experiments, kinetic isotope effects, and computational modeling, provide insight into the reaction pathways and catalyst-substrate interactions governing regioselectivity.

Overall, this work not only highlights the synthetic potential of visible-light photoredox catalysis but also establishes new paradigms for regioselective C-C bond construction, offering scalable and sustainable alternatives to classical methods and laying a foundation for future innovations in organic synthesis.