O-C Glycoside Rearrangement through Time-Controlled Electrochemical Flow Strategy: Switching between Kinetics and Thermodynamics

We herein report time-controlled O-C glycoside rearrangement in flow-electrochemical microreactors, focusing on kinetic and thermodynamic selectivity. The selective synthesis of phenolic O- and C-glycosides has been explored using O-C glycoside rearrangement. We investigated the time-control of O-C glycoside rearrangement using a flow microreactor, which allows for second-scale reaction control. The electrochemical approach demonstrated that shortening the residence time leads to the selective synthesis of O-glycosides, while longer times favor the formation of C-glycosides. Kinetic studies revealed that substituents on the phenol ring affect the rate of O-glycoside formation and its rearrangement to C-glycosides. Finally, continuous flow synthesis was demonstrated, showcasing the scalability and utility of this method for producing bioactive substances.