Excited-state reactivity of 4-hydroxycoumarins: unlocking new photochemical transformation

This PhD thesis examines how light excitation can be harnessed to reprogram the intrinsic reactivity of 4-hydroxycoumarins, compounds traditionally known for their ground-state nucleophilic behavior. By revealing how photochemical activation alters their fundamental reactivity patterns, this thesis establishes the unrecognized photoreactivity of 4-hydroxycoumarins in organic synthesis. Firstly, we revealed that, upon deprotonation and excitation with purple light, 3-substituted 4-hydroxycoumarins reach an excited state and act as strong single-electron transfer (SET) reductants, generating radicals from stable substrates. This newfound reactivity enables the direct synthesis of 3,3-disubstituted 2,4-chromandiones via a radical dearomatization process. By enabling the incorporation of alkyl and perfluoroalkyl fragments, this protocol offers a straightforward and mild route to access synthetically valuable chromanone scaffolds featuring a quaternary stereocenter. Based on our findings in the first project, we modified 4-hydroxycoumarins to design 3-thioaryl-4-hydroxycoumarins, a new family of cost-effective organic photocatalysts that leverage a stabilized charge-transfer (CT) excited state to achieve both strong reducing power and efficient energy transfer (EnT) behavior. The spatial separation of the HOMO and LUMO stabilizes the CT state, enhancing SET reactivity (E*red = −3.08 V vs. SCE) while maintaining a sufficiently high triplet energy (ET = 67 kcal mol−1) for EnT-driven transformations. This dual reactivity enables the activation of redox-inert substrates (Ered < −2.8 V vs. SCE) via SET reduction, generating radicals suitable for diverse C─S, C─P, C─B, and C─C bond-forming transformations, alongside EnT-based processes such as E/Z olefin isomerization and [2+2] photocycloadditions. Mechanistic studies, supported by photophysical and theoretical analyses, confirmed the catalyst’s bifunctionality. In conclusion, this work demonstrates that by exploiting light to control electronic excitation, 4-hydroxycoumarins can be transformed from simple ground-state nucleophiles into versatile photoactive scaffolds that enable previously inaccessible radical transformations.