Separating Proton and Electron Transfer Effects in Three-Component Concerted Proton-Coupled Electron Transfer Reactions

Abstract

Multiple-site concerted proton-electron transfer (MS-CPET) reactions were studied in a three-component system. 1-Hydroxy-2,2,6,6-tetramethylpiperidine (TEMPOH) was oxidized to the stable radical TEMPO by electron transfer to ferrocenium oxidants coupled to proton transfer to various pyridine bases. These MS-CPET reactions contrast with the usual reactivity of TEMPOH by hydrogen atom transfer (HAT) to a single e^-/H⁺ acceptor. The three-component reactions proceed by pre-equilibrium formation of a hydrogen-bonded adduct between TEMPOH and the pyridine base, and the adduct is then oxidized by the ferrocenium in a bimolecular MS-CPET step. The second-order rate constants, measured using stopped-flow kinetic techniques, spanned 4 orders of magnitude. An advantage of this system is that the MS-CPET driving force could be independently varied by changing either the pK_a of the base or the reduction potential (E°) of the oxidant. Changes in ΔG°_MS-CPET from either source had the same effect on the MS-CPET rate constants, and a combined Brønsted plot of ln(k_MS-CPET) vs ln(K_eq) was linear with a slope of 0.46. These results imply a synchronous concerted mechanism, in which the proton and electron transfer components of the CPET process make equal contributions to the rate constants. The only outliers to the Brønsted correlation are the reactions with sterically hindered pyridines, which apparently hinder the close approach of proton donor and acceptor that facilitates MS-CPET. These three-component reactions are compared with a related HAT reaction of TEMPOH, with the 2,4,6-tri-tert-butylphenoxyl radical. The MS-CPET and HAT oxidations of TEMPOH at the same driving force occurred with similar rate constants. While this is an imperfect comparison, the data suggest that the separation of the proton and electron to different reagents does not significantly inhibit the proton-coupled electron transfer process.

Figure 1

(a) IR spectra of TEMPOH in CH₂Cl₂ with increasing concentrations of py, showing decreasing absorbance at 3582 cm⁻¹ due to free TEMPOH and increasing intensity in the broad band at 3237 cm⁻¹ due to the TEMPOH^…py hydrogen bonded adduct. The sharp feature at 3150 cm⁻¹ is from the pyridine aromatic C-H stretches. (b) Plot of [Adduct]/[TEMPOH] vs. [R-py] for various substituted pyridines. Linear fits to the data are shown; the slope corresponds to the hydrogen bond equilibrium constant (K_HB). 2,6-Lutidine = 2,6-dimethylpyridine; DMAP = 4-dimethylaminopyridine.

Figure 2

(a) Optical absorption spectra showing the loss of the Cp₂Fe⁺ absorbance (over 1 second) at 618 nm. (b) Single wavelength trace at 618 nm and fit to single exponential.

Figure 3

Plot of ln (k₂) vs ln (K_eq) for TEMPOH oxidations by the combination of a pyridine base with [Cp₂Fe]BF₄ (blue squares, ), [(MeCp)₂Fe]PF₆ (red circle, ), and [Cp(Cp*)Fe]PF₆ (green triangles, ) in CH₂Cl₂, with the numbers corresponding to the entries in Table 1. The purple diamond ( ) represents the oxidation with [Cp₂Fe]BF₄ and 2,6-lutidine. The orange inverted triangle ( ) marks the HAT reaction between TEMPOH and ^tBu₃PhO· (in CCl₄).

Figure 4

Grunwald analysis of the disparity of a two-component concerted reaction. In (b), a hyperbolic paraboloid E(x,y) represents the free energy surface. The mean reaction progress is given by the parameter x (from 0 to 1), shown as the solid arrow in (a), the More O’Farrell diagram for MS-CPET and as r → p in (c). The perpendicular ‘disparity’ axis, 0 < y < 1 in shown in (a) as a double-headed dotted arrow. The disparity is indicated by the displacement of the transition state along y, as the curvature of the reaction progress arrow toward one of the corners. Figures b) and c) reproduced from with permission.

Scheme 1

MS-PCET from TEMPOH to pyridine bases and ferrocenium oxidants

Scheme 2

Equilibrium formation of hydrogen-bonded adduct (top), followed by oxidation with an outer sphere oxidant (bottom), and the rate law for this mechanism.^{a a}Equation (1) applies when [py] ≫ [TEMPOH].

Scheme 3

Square scheme showing free energies of proton transfers (horizontal axis) and electron transfers (vertical axis) for the termolecular MS-CPET TEMPOH oxidation with Cp₂Fe⁺ and 4-Me₂Npy in MeCN.^, The diagonal gives the ΔG^‡ from the measured k₂ and the Eyring equation.