Computational Study Revealing a Substrate–O ₂ –Solvent Cascade Activation Mechanism for Cu-Catalyzed Aerobic Epoxidation of Tertiary Allylic Alcohols and Ethers

Cu-catalyzed aerobic epoxidation offers cost-effective access to epoxides, a class of versatile chemical building blocks. Herein, a computational mechanistic study was performed to investigate Cu-catalyzed aerobic epoxidation of tertiary allylic alcohols and ethers. In contrast to the previously proposed solvent–O 2 cascade activation and the O 2 -activation mechanisms, a substrate–O 2 –solvent cascade activation mechanism was revealed for not only high-strained substrates but also low- and nonstrained substrates tested herein. Specifically, it involves an induction period for the in situ generation of the actual catalyst, a Cu(II)-alkylperoxide complex derived from solvent 1,4-dioxane. Three substrate-activation pathways, depending on the substrate strain and the presence or absence of an allylic hydroxyl group, were found to be operative in this period. For the actual catalytic epoxidation, the mononuclear Cu(II) pathway was found to be favored over the dinuclear Cu(III)-oxo pathway and mononuclear Cu(I) pathways. Meanwhile, apart from serving as a solvent, 1,4-dioxane plays dual roles, i.e., as a carbon source for the generation of an active catalyst and as a reductant to accept the unreactive oxygen atoms of O 2 . The new mechanistic framework, along with the calculated energy barriers, is consistent with both the reported radical trapping experiments and the performance observed for three types of substrates.