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 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, which is then oxidized by the ferrocenium in a bimolecular MS-CPET step. The second order rate constants, measured using stopped-flow kinetic techniques, spanned four orders of magnitude. An advantage of this system is that the MS-CPET driving force could be independently varied by changing either the pKa 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(kMS-CPET) vs. ln(Keq) 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 outlier 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 hydrogen atom transfer 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 PCET process.

A new strategy to efficiently cleave and form C–H bonds using proton-coupled electron transfer

“…The shallow slope for the C–H bond oxidations of only 0.21 ± 0.01, however, is quite unusual. This slope, the Brønsted α, is much lower than the ~0.5 typically observed for reactions at polar O–H or N–H bonds ( 4 , 5 , 7 ) and for HAT reactions of C–H bonds ( 3 ). A possible explanation is that the transition state for MS-CPET involves concerted but asynchronous transfer of the proton and electron; specifically, that the transition states for these reactions could have more PT or bond breaking character.…”

“…All oxidants used were hexafluorophosphate (PF 6 − ) salts. Aminium ( 7 ) and ferrocenium ( 4 ) oxidants were prepared as described previously. CoCp* 2 was purchased from Sigma-Aldrich and purified before use by dissolving the metallocene in a minimal amount of pentane, filtering, and concentrating the filtrate in vacuo in a N 2 -filled dry box.…”

A Continuum of Proton-Coupled Electron Transfer Reactivity

“…(B) Plot of ln( k MS CPET ) vs ln( K eq ). Part (B) reproduced with permission from ref 32. Copyright 2017 American Chemical Society.…”

“…32 The formally termolecular reaction occurs via a rapidly formed TEMPO-H⋯py hydrogen-bonded adduct, which was quantified by IR spectroscopy. The rate-determining step is then PT across the hydrogen bond to the pyridine concerted with ET to the ferrocenium (Fc + ).…”

“…32 Each pyridine/ferrocenium pair has an effective BDFE, following the thermochemical framework described above (Scheme 2). This BDFE eff then gives the driving force for the overall reaction for each oxidant/base combination ( Δ G ° MS-CPET , K eq ).…”