Debate of Nucleophilic versus Electrophilic Oxidative Aldehyde Deformylation by Mononuclear Nonheme Iron(III)-Peroxo and Iron(IV)-Oxo Complexes

High-valent iron(IV)-oxo species are fleeting intermediates that perform vital reactions in enzymatic catalysis. In contrast, heme and nonheme iron(III)-peroxo intermediates usually act as nucleophiles and are converted to high-valent iron-oxo intermediates for electrophilic oxidation reactions. Herein, we report a study on aldehyde deformylation reactions of 2-phenylpropionaldehyde (2-PPA) and its derivatives by iron(III)-peroxo complexes bearing tetramethylated cyclam (TMC) analogues, including [FeIII(O2)(12-TMC)]+ (1), [FeIII(O2)(13-TMC)]+ (2), and [FeIII(O2)(14-TMC)]+ (3). Reactivity studies by employing deuterated substrates, such as α-[D1]-2-phenylpropionaldehyde and aldehyde-[D]-2-phenylpropionaldehyde, demonstrate that deformylation of 2-PPA by the nonheme iron(III)-peroxo complexes occurs via abstraction of the stronger aldehyde C-H atom, rather than the expected nucleophilic attack or weaker α-C-H atom abstraction reactions. Interestingly, the preference for aldehyde C-H atom abstraction is retained during the deformylation of 2-PPA by iron(IV)-oxo complexes, i.e., [FeIV(O)(13-TMC)]2+ (4) and [FeIV(O)(N4Py)]2+ (5). DFT calculations reproduce the experimental trends in reactivity and reveal that the peroxide O-O bond is cleaved to form an iron(III)-dioxyl species that conducts aldehyde C-H bond abstraction; this chemoselectivity is achieved through stabilizing noncovalent interactions between the oxidants and the aromatic ring of the substrate that positions the aldehyde in close proximity to the FeIII-O2/FeIV═O cores. These new experimental and theoretical findings together with the previous demonstrations of the ability of 1-3 in hydrogen atom transfer, oxygen atom transfer, and cis-dihydroxylation reactions highlight that iron(III)-peroxo cores are not inherently nucleophiles and can have more important functions in chemical and biological oxidation reactions, rather than acting as transient species en route to high-valent metal-oxo intermediates.