DFT Mechanistic Insights into Aldehyde Deformylations with Biomimetic Metal–Dioxygen Complexes: Distinct Mechanisms and Reaction Rules

[Image: see text] Aldehyde deformylations occurring in organisms are catalyzed by metalloenzymes through metal–dioxygen active cores, attracting great interest to study small-molecule metal–dioxygen complexes for understanding relevant biological processes and developing biomimetic catalysts for aerobic transformations. As the known deformylation mechanisms, including nucleophilic attack, aldehyde α-H-atom abstraction, and aldehyde hydrogen atom abstraction, undergo outer-sphere pathways, we herein report a distinct inner-sphere mechanism based on density functional theory (DFT) mechanistic studies of aldehyde deformylations with a copper (II)–superoxo complex. The inner-sphere mechanism proceeds via a sequence mainly including aldehyde end-on coordination, homolytic aldehyde C–C bond cleavage, and dioxygen O–O bond cleavage, among which the C–C bond cleavage is the rate-determining step with a barrier substantially lower than those of outer-sphere pathways. The aldehyde C–C bond cleavage, enabled through the activation of the dioxygen ligand radical in a second-order nucleophilic substitution (S(N)2)-like fashion, leads to an alkyl radical and facilitates the subsequent dioxygen O–O bond cleavage. Furthermore, we deduced the rules for the reactions of metal–dioxygen complexes with aldehydes and nitriles via the inner-sphere mechanism. Expectedly, our proposed inner-sphere mechanisms and the reaction rules offer another perspective to understand relevant biological processes involving metal–dioxygen cores and to discover metal–dioxygen catalysts for aerobic transformations.