Homolysis

Organic chemistry

Combinatorial chemistry

Photoredox catalysis

Electrophile

Photocatalysis

Radical

Catalysis

Nucleophile

Chemistry

Alkyl

SN2 reaction

Photochemistry

Nature Chemistry

Chemists extensively use free radical reactivity for applications in organic synthesis, materials science, and life science. Traditionally, generating radicals requires strategies that exploit the bond dissociation energy or the redox properties of the precursors. Here, we disclose a photochemical catalytic approach that harnesses different physical properties of the substrate to form carbon radicals. We use a nucleophilic dithiocarbamate anion catalyst, adorned with a well-tailored chromophoric unit, to activate alkyl electrophiles via an SN2 pathway. The resulting photon-absorbing intermediate affords radicals upon homolytic cleavage induced by visible light. This catalytic SN2-based strategy, which exploits a fundamental mechanistic process of ionic chemistry, grants access to open-shell intermediates from a variety of substrates that would be incompatible with or inert to classical radical-generating strategies. We also describe how the method’s mild reaction conditions and high functional group tolerance could be advantageous for developing C–C bond-forming reactions, for streamlining the preparation of a marketed drug, for the late-stage elaboration of biorelevant compounds and for enantioselective radical catalysis. The SN2 reaction, a fundamental process associated with ionic chemistry, can be incorporated into a photochemical approach to creating radicals from alkyl electrophiles. This method occurs readily under visible-light irradiation, exhibits broad functional-group tolerance, and enables the formation of open-shell intermediates from substrates that are incompatible with traditional radical-generating strategies.

Photochemical generation of radicals from alkyl electrophiles using a nucleophilic organic catalyst