A General Light-Driven Organocatalytic Platform for the Activation of Inert Substrates

Due to their strong covalent bonds and low reduction potentials, activating inert substrates is challenging. Recent advances in photoredox catalysis offered a number of solutions, each of which useful for activating specific inert bonds. Developing a general catalytic platform that can consistently target a broad range of inert substrates would be synthetically useful. Herein, we report a readily available indole thiolate organocatalyst that, upon excitation with 405 nm light, acquires a strongly reducing power. This excited-state reactivity served to activate, by single-electron reduction, strong C-F, C-Cl, and C-O bonds in both aromatic and aliphatic substrates. This catalytic platform was versatile enough to promote the reduction of generally recalcitrant electron-rich substrates (E-red<-3.0 V vs SCE), including arenes that afforded 1,4-cyclohexadienes. The protocol was also useful for the borylation and phosphorylation of inert substrates with a high functional group tolerance. Mechanistic studies identified an excited-state thiolate anion as responsible of the highly reducing reactivity.

Automated summary

Activating inert substrates is challenging due to their strong covalent bonds and low reduction potentials. Recent advances in photoredox catalysis have provided solutions to activate specific inert bonds. However, developing a general catalytic platform that can consistently target a broad range of inert substrates would be synthetically useful. This study reports the use of an indole thiolate organocatalyst that, when excited with 405 nm light, becomes strongly reducing and able to activate strong C-F, C-Cl, and C-O bonds in both aromatic and aliphatic substrates. Mechanistic studies revealed an excited-state thiolate anion responsible for the highly reducing reactivity.