Dichotomous Hydrogen Atom Transfer vs Proton-Coupled Electron Transfer During Activation of X–H Bonds (X = C, N, O) by Nonheme Iron–Oxo Complexes of Variable Basicity

Abstract

We describe herein the hydrogen-atom transfer (HAT)/ proton-coupled electron-transfer (PCET) reactivity for FeIV-oxo and FeIII-oxo complexes (1–4) that activate C-H, N-H, and O-H bonds in 9,10 dihydroanthracene (S1), dimethylformamide (S2), 1,2 diphenylhydrazine (S3), p-methoxyphenol (S4), and 1,4-cyclohexadiene (S5). In 1–3, the iron is pentacoordinated by tris[N'-tert-butylureaylato)-N-ethylene]aminato ([H3buea]3−) or its derivatives. These complexes are basic, in the order 3 >> 1 > 2. Oxidant 4, [FeIVN4Py(O)]2+ (N4Py: N,N-bis(2-pyridylmethyl)-bis(2-pyridyl) methylamine), is the least basic oxidant. The DFT results match experimental trends and exhibit a mechanistic spectrum ranging from concerted HAT and PCET reactions to concerted-asynchronous proton transfer (PT) / electron transfer (ET) mechanisms, all the way to PT. The singly occupied orbital along the O---H---X (X= C, N, O) moiety in the TS shows clearly that in the PCET cases, the electron is transferred separately from the proton. The Bell-Evans-Polanyi principle does not account for the observed reactivity pattern, as evidenced by the scatter in the plot of calculated barrier vs. reactions driving forces. However, a plot of the deformation energy in the TS vs. the respective barrier provides a clear signature of the HAT/PCET dichotomy. Thus, in all C-H bond activations, the barrier derives from the deformation energy required to create the TS, whereas in N-H/O-H bond activations, the deformation energy is much larger than the corresponding barrier, indicating the presence of stabilizing interaction between the TS fragments. A valence bond model is used to link the observed results with the basicity/acidity of the reactants.

Mono- and binuclear non-heme iron chemistry from a theoretical perspective

“…In a theoretical work, Usharani et al [179] linked the basicity of the Fe IV =O oxidant with a mechanism for HAA, i.e., the concerted H-atom transfer (HAT) versus the proton-coupled electron transfer (PCET). Using valence bond based arguments, they concluded that a less basic oxidant exhibits a higher oxyl character on the oxo group that is required for the more concerted HAT (more homolytic)…”

An attempt to evaluate the effect of proton-coupled electron transfer on the H-abstraction step of the reaction between 1,1-dimethylhydrazine and cytochrome P450 compound I

“…We conjectured that the observed small reaction barrier could be well explained in terms of the hydrogen atom transfer (HAT) mechanism [18]. However, we later learned from Usharani et al's computational analysis of the H-abstraction reactions of synthetic nonheme iron-oxo complexes that spin natural orbital (SNO) analysis provides a useful orbital signature of PCET in the reactions of iron-oxo complexes [19]. Thus, when PCET takes place, the SNO is not localized onto the reacting X H bond (X C, N, ...), but rather is a or mixed -lone-pair orbital that does not point to the oxo unit [19,20].…”

“…However, we later learned from Usharani et al's computational analysis of the H-abstraction reactions of synthetic nonheme iron-oxo complexes that spin natural orbital (SNO) analysis provides a useful orbital signature of PCET in the reactions of iron-oxo complexes [19]. Thus, when PCET takes place, the SNO is not localized onto the reacting X H bond (X C, N, ...), but rather is a or mixed -lone-pair orbital that does not point to the oxo unit [19,20]. We felt that using the SNO approach and other theoretical techniques, the H-abstraction from UDMH by P450 Cpd I should be further studied in greater depth.…”

cPCET versus HAT: A Direct Theoretical Method for Distinguishing X–H Bond‐Activation Mechanisms

“…Reactions in which electron and proton travel together as a true hydrogen atom will be called hydrogen atom transfer (HAT); the more general term cPCET will be used only when proton and electron are transferred in concert, but do not travel together, a definition similar to the one used by Shaik and co‐workers 7a. Scheme 1 shows two representative cases, which we will discuss in detail below.…”