Developing new and improved methods for synthesizing drug candidates from petrochemical feedstocks has been a long-standing interest for chemists. We report a new electrochemical synthetic methodology that reproduces the unique reaction environment observed in photoredox catalysis. Photoredox catalysis relies upon the unique photo-physical properties of photocatalysts, as they can act as both a strong oxidant and reductant in a catalytic cycle. We postulated use of alternating current electrolysis (ACE) could effectively mimic the transition between two single electron transfer (SET) in photoredox catalysis. Our study examined the trifluoromethylation of aryl and alkene C-H bonds afford trifluoromethylene targets, a common motif found in a range of pharmaceutical drug candidates. The methodology diverges from previously reported paired electrolysis as the intermediates are no longer required to migrate between the two electrodes, but rather react at the same electrode upon switching the potential. Therefore, the new protocol allows for short-lived intermediates to react immediately upon the electrode polarity reversal, which was previously unobtainable. Excitingly, our innovative ACE approach allows the frequency to be tuned, and hence the time between the redox events controlled for individual target compounds. This unique property of ACE provides superior control over the reaction conditions than either conventional paired electrolysis or photoredox catalysis.

Alternating current electrolysis (ACE) for organic synthesis: Trifluoromethylation of (hetero)arenes and alkenes

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.