An Unorthodox Enolate-Triggered Radical Relay Directs the Chemo Upgrading of Levulinic Acid Into Citramalic Acid

We report a transition-metal-free and highly selective chemical transformation of levulinic acid into citramalic acid via t-butoxide-mediated enolate chemistry, complementing both the biotransformation of glucose and glycerol using E. coli as well as transition-metal-catalyzed processes based on levulinic acid. The atypical behavior of t-butoxide-classically recognized as a base that favors kinetic enolate formation in carbonyl chemistry-proves crucial for accessing the thermodynamic enolate under elevated temperatures and extended reaction times, thereby directing the reaction toward citramalic acid as the major product. Radical-trapping experiments with TEMPO (2,2,6,6-tetramethylpiperidine 1-oxyl) and benzoic acid significantly diminished the product yield, indicating the involvement of radical intermediates in the initial oxygenation sequence and providing clear mechanistic insight into the operative pathway. Moreover, citramalic acid serves as a sustainable, bio-based platform chemical that is amenable to downstream valorization into high-value feedstocks, such as unnatural amino acid derivative and itaconic acid.