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. 2019 Jul 10;141(27):10777-10787.
doi: 10.1021/jacs.9b04303. Epub 2019 Jun 27.

Transition State Asymmetry in C-H Bond Cleavage by Proton-Coupled Electron Transfer

Julia W Darcy  1 , Scott S Kolmar  1 , James M Mayer  1
Affiliations

Transition State Asymmetry in C-H Bond Cleavage by Proton-Coupled Electron Transfer

Julia W Darcy et al. J Am Chem Soc. .

Abstract

The selective transformation of C-H bonds is a longstanding challenge in modern chemistry. A recent report details C-H oxidation via multiple-site concerted proton-electron transfer (MS-CPET), where the proton and electron in the C-H bond are transferred to separate sites. Reactivity at a specific C-H bond was achieved by appropriate positioning of an internal benzoate base. Here, we extend that report to reactions of a series of molecules with differently substituted fluorenyl-benzoates and varying outer-sphere oxidants. These results probe the fundamental rate versus driving force relationships in this MS-CPET reaction at carbon by separately modulating the driving force for the proton and electron transfer components. The rate constants depend strongly on the pKa of the internal base, but depend much less on the nature of the outer-sphere oxidant. These observations suggest that the transition states for these reactions are imbalanced. Density functional theory (DFT) was used to generate an internal reaction coordinate, which qualitatively reproduced the experimental observation of a transition state imbalance. Thus, in this system, homolytic C-H bond cleavage involves concerted but asynchronous transfer of the H+ and e-. The nature of this transfer has implications for synthetic methodology and biological systems.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
(A) General reaction scheme for the oxidation of Flr(R)CO2− substrates. Reactions were performed with an excess of carboxylate, generated in situ with TBAOH (as a solution in MeOH). Absorbance spectra were monitored on a stopped-flow following the disappearance of the colored aminium and ferrocenium oxidants. (B) Representative absorbance versus time data set monitoring the reaction of N(ArOMe)3•+ with Flr(OMe)CO2−. The inset shows the absorbance at the λmax of the oxidant, 752 nm, versus time, and the fit to an exponential function using SpecFit global fitting software. (C) Plot of the logarithm of the MS-CPET rate constants (kMS‑CPET = k2/2) versus changes in driving force for all substrates over a range of oxidants. Δlog(Keq) = −ΔΔG°rxn/2.303RT and ΔΔG°rxn = ΔBDFECH(CO2H) − 1.37ΔpKa(CO2H) − 23.06Eox (see text and Scheme 2). The Δlog(Keq) for the reaction of the R = H compound with FeCp*2+ has been set equal to zero, and all other values are relative to that based on changes in BDFECH and pKa,COOH (see the Supporting Information for all values). Uncertainty in the last decimal is shown in parentheses. (D) Plot of MS-CPET rate constants versus changes in driving force for the four substrates with a single oxidant (FeCp2+).
Figure 2.
Figure 2.
Comparison of the DFT-computed internal reaction coordinates and transition states for intramolecular PT in Flr(H)CO2− (A, C, and E) and for the MS-CPET reaction of Flr(H)CO2− and N(ArBr)3•+ (B, D, and F). (A and B) The transition state occurs at x = 0 along the reaction coordinate. Proceeding to negative values along the x-axis leads toward reactants, while proceeding to positive values leads to products. Black “○” show potential energy (ΔE) along the reaction coordinate. (C and D) Red “□” show the distance between the fluorenyl proton and the carboxylate oxygen along the reaction coordinate, which is a measure of proton transfer. For intramolecular PT, the fluorenyl proton has proceeded 76% toward the carboxylate oxygen. For MS-CPET, the fluorenyl proton has proceeded 44% toward the carboxylate oxygen. (E and F) Blue “Δ” show the sum of the CCC bond angles along the fluorenyl carbon along the reaction coordinate, which is a measure of electronic reorganization. For intramolecular PT, the sum of the fluorenyl CCC bond angles has proceeded 45% toward the final geometry. For MS-CPET, the sum of the fluorenyl CCC bond angles has proceeded 29% toward the final geometry.
Figure 3.
Figure 3.
(A) A More O’Ferrall–Jencks plot for intramolecular proton transfer in Flr(H)CO2−. The progress of the proton transfer and electronic reorganization at the transition state (‡) are noted with dashed lines. (B) A double More O’Ferrall–Jencks plot for the MS-CPET reaction of Flr(H)CO2− with an outer-sphere oxidant. As in part (A), each of the two horizontal planes illustrates the progress in the proton transfer coordinate and in the electronic reorganization coordinate. The jump from the bottom to the top plane represents the electron transfer to the oxidant, an essentially instantaneous step that takes the system from one electronic state to another.
Scheme 1.
Scheme 1.. MS-CPET at Fluorenyl-benzoates Flr(R)CO
2−, R = CF3, H, OMe, NH2a aThe driving forces for proton and electron transfer can be modulated by changing the pKa of the internal base and the E1/2 of the external oxidant, respectively. Oxidation leads to the formation of the carbon centered radical, which is subsequently converted to the corresponding lactone.
Scheme 2.
Scheme 2.. Thermochemical Cycle To Determine the Relative Free Energies of MS-CPET Oxidation of the Fluorenyl C–H Bonds
See this image and copyright information in PMC

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