Hydrogen atom transfer (HAT) is one of the most fundamental chemical reactions: A–H + B → A + H–B. It is a key step in a wide range of chemical, environmental, and biological processes. Traditional HAT involves p-block radicals such as tBuO• abstracting H• from organic molecules. More recently, it has been recognized that many transition metal species undergo HAT. This has led to a broader perspective, with HAT viewed as one type of proton-coupled electron transfer (PCET).
When transition metal complexes oxidize substrates by removing H• (≡ e– and H+), typically the electron transfers to the metal and the proton transfers to a ligand. Two examples are shown in the Figure: iron-imidazolinate and vanadium-oxo complexes. Although such reagents do not “look like” main group radicals, they have the same pattern of reactivity. For instance, their HAT rate constants parallel the A–H bond strengths within a series of similar reactions. Just like main group radicals, they abstract H• much faster from O–H bonds than from C–H bonds of the same strength. This shows that driving force is not the only determinant of reactivity.
We have found that HAT reactivity is well described using a Marcus-theory approach. In the simplest model, the cross relation, kAH/B = (kAH/AkBH/BKeqf)½, predicts the rate constant for AH + B in terms of the self-exchange rate constants (kAH/A for AH + A) and the equilibrium constant. For a variety of transition metal oxidants, kAH/B is predicted within one or two orders of magnitude with only a few exceptions. For 36 organic reactions of oxyl radicals, kAH/B is predicted with an average deviation of a factor of 3.8, and within a factor of 5 for all but six of the reactions. These reactions involve both O–H or C–H bonds, occur either in water or organic solvents, and over a range of 1028 in Keq and 1013 in kAH/B. The treatment of organic reactions of O–H bonds includes the well-established kinetic solvent effect on HAT reactions. This is one of a number of secondary effects that the simple cross relation does not include, such as hydrogen tunneling and the involvement of precursor and successor complexes. Various case studies are described, applying the cross relation and illustrating some of these additional issues.
The success of the cross relation, despite it being a quite simplified treatment, shows that the Marcus approach based on free energies and intrinsic barriers captures much of the essential chemistry of HAT reactions. Among the insights derived from the analysis is that reactions correlate with ΔG°, not with bond enthalpies as has long been assumed. Also in contrast to common intuition, the radical character or spin state of an oxidant is not found to be a primary determinant of HAT abstracting ability. The intrinsic barriers for HAT reactions can be understood, at least in part, as Marcus-type inner-sphere reorganization energies. The intrinsic barriers for cross reactions are accurately derived from the HAT self-exchange rate constants, which is a remarkable and unprecedented result for any type of chemical reaction other than electron transfer. The Marcus cross relation thus provides a valuable new framework for understanding and predicting HAT reactivity.