Electrochemical SNAr Unlocks Access to Chemical Space with High Energy Efficiency
- josephderos
- 6 hours ago
- 1 min read
Nucleophilic aromatic substitution (SNAr) is one of the most widely utilized synthetic reactions for the discovery and production of life-saving pharmaceuticals; yet, only a fraction of chemical space can be accessed due to the electronic requirements of the electrophilic arene fragment. A completely orthogonal approach that unlocks electron-rich arene substrates would exponentially increase access to bioactive molecular space, but must address critical challenges associated with robustness, scalability and energy efficiency.
In this preprint, Brett and Jillian demonstrate that an electrochemical strategy that spatially separates redox events at electrodes prevents back-electron transfer to afford the desired C–N bond, unlocking electrochemical SNAr (e-SNAr) of electron-rich arene substrates with azoles. Importantly, our developed method operates under air, at room temperature, is highly scalable (50 mmol), and highly energy efficient (catalytic charge).
For a link to the preprint: