Methylation of Heterocycles via Iodanyl Radical-Mediated Kolbe Decarboxylation

Exploiting Kolbe decarboxylation for methyl-radical transformations beyond conventional dimerization remains a longstanding synthetic challenge. Herein, we address this challenge by switching from classical Kolbe decarboxylation to iodanyl radical-mediated electrolysis, which enables decarboxylative methylation of heterocycles on sustainable graphite anodes and is scalable to gram quantities. This strategy also supports CD3-methylation of heterocycles and the late-stage methylation of biomolecules. Nearly two centuries after Kolbe decarboxylation, this organoiodine-mediated protocol overcomes its limitations, opening a route to lead compounds.