A Chemical Space Perspective on Diastereomeric Barriers in Alkylperoxy-to-Hydroperoxyalkyl Isomerization

Abstract

Abstract Low-temperature hydrocarbon autoxidation involves radical intermediates whose reactivity depends not only on the stereochemistry of the intermediates themselves, but also on that of the transient species encountered along the reaction path. This study offers large-scale evidence for the importance of stereochemistry in low-temperature autoxidation by propagating stereochemical information from 498 C1–C7 hydrocarbons through radical formation, O2 addition, and the isomerization of alkylperoxy (ROO•) radicals to hydroperoxyalkyl (•QOOH) radicals. The resulting data set comprises density-functional-theory-level data for 5356 species, including 2324 cyclic diastereomeric transition states associated with 1162 unique ROO• → •QOOH isomerization reactions, with transition-state connectivity confirmed by intrinsic reaction coordinate analysis. Explicit stereochemical treatment reveals that diastereomeric pathways may be either nearly degenerate or separated by more than 60 kcal/mol, with the magnitude of these differences governed by local steric strain, ring constraint, and the environments of the peroxyl-bearing and H-abstraction centers. These results show that constitutionally collapsed molecular representations can systematically miss kinetically relevant reactive channels and provide a foundation for stereochemistry-aware mechanism generation, rate estimation, and predictive combustion modeling.