Mediated Electrochemical Oxidation of Nucleosides to Their 5’‐Carboxylic Acid Derivatives

Nucleoside 5’‐carboxylic acids are important synthetic targets, but most existing methods to access these compounds use (super)stoichiometric chemical oxidants to oxidize the primary alcohol. The present study introduces an aminoxyl‐mediated electrochemical method for oxidation of nucleosides and ribosugars to afford their 5’‐carboxylic acid derivatives. The optimized conditions employ 4‐acetamido‐2,2,6,6‐tetramethylpiperidine 1‐oxyl (ACT) as the aminoxyl mediator in a water/acetonitrile solvent mixture with tetraethylammonium bicarbonate or monohydrogen phosphate as a base within an undivided electrolysis cell. The reaction tolerates diverse functionality at the nucleobase and sugar positions and is showcased in the oxidation of 10 different substrates, including a 10 g‐scale oxidation of 2’‐O‐methylcytidine.