Novel β-Pathways in the Low-Temperature Oxidation of Tetrahydrofuran Discovered by Automated Exploration

Abstract Low-temperature oxidation reactions are central to fuel and combustion chemistry, yet the transient radical intermediates that govern them remain difficult to interrogate experimentally. The oxidation of tetrahydrofuran (THF) to ketohydroperoxide (KHP) is a paradigmatic system in which established mechanistic proposals fail to reproduce experimentally observed product distributions. Six KHPs are accessible through THF oxidation, three following molecular oxygen addition to the α carbon and three following addition to the β carbon. Although α-addition is both kinetically and thermodynamically preferred and has been characterized in detail, the experimental β-derived KHP abundances remained incompletely explained by existing models. Here the THF-to-KHP network is mapped with an automated reaction exploration algorithm that computes activation energies and reaction thermodynamics for all KHP-forming pathways and for potentially competitive off-target channels. The exploration recovers previously reported reactions in quantitative agreement with the literature while identifying hydrogen-transfer and isomerization reactions that connect the α and β branches of the network. The energetic accessibility of these interconnecting reactions is consistent with the reported abundance of β-pathway KHPs and identifies specific channels that should be included in future kinetic models of THF oxidation.