Continuous Flow Electrochemistry Enables Practical and Site‐Selective C−H Oxidation

Abstract The selective oxygenation of ubiquitous C(sp 3 )−H bonds remains a highly sought‐after method in both academia and the chemical industry for constructing functionalized organic molecules. However, it is extremely challenging to selectively oxidize a certain C(sp 3 )−H bond to afford alcohols due to the presence of multiple C(sp 3 )−H bonds with similar strength and steric environment in organic molecules, and the alcohol products being prone to further oxidation. Herein, we present a practical and cost‐efficient electrochemical method for the highly selective monooxygenation of benzylic C(sp 3 )−H bonds using continuous flow reactors. The electrochemical reactions produce trifluoroacetate esters that are resistant to further oxidation but undergo facile hydrolysis during aqueous workup to form benzylic alcohols. The method exhibits a broad scope and exceptional site selectivity and requires no catalysts or chemical oxidants. Furthermore, the electrochemical method demonstrates excellent scalability by producing 115 g of one of the alcohol products. The high site selectivity of the electrochemical method originates from its unique mechanism to cleave benzylic C(sp 3 )−H bonds through sequential electron/proton transfer, rather than the commonly employed hydrogen atom transfer (HAT).