Direct electrochemical hydrodefluorination of trifluoromethylketones enabled by non-protic conditions

CF2H groups are unique due to the combination of their lipophilic and hydrogen bonding properties. The strength of H-bonding is determined by the group to which it is appended. Several functional groups have been explored in this context including O, S, SO and SO2 to tune the intermolecular interaction. Difluoromethyl ketones are under-studied in this context, without a broadly accessible method for their preparation. Herein, we describe the development of an electrochemical hydrodefluorination of readily accessible trifluoromethylketones. The single-step reaction at deeply reductive potentials is uniquely amenable to challenging electron-rich substrates and reductively sensitive functionality. Key to this success is the use of non-protic conditions enabled by an ammonium salt that serves as a reductively stable, masked proton source. Analysis of their H-bonding has revealed difluoromethyl ketones to be potentially highly useful dual H-bond donor/acceptor moieties.

Automated summary

CF2H groups are unique in their combination of lipophilic and hydrogen bonding properties, with the strength of hydrogen bonding determined by the attached group. Electrochemical hydrodefluorination has been developed as a method for the preparation of under-studied difluoromethyl ketones. Analysis has shown difluoromethyl ketones to potentially be highly useful as dual hydrogen bond donor/acceptor moieties.