C–H oxidation in fluorenyl benzoates does not proceed through a stepwise pathway: revisiting asynchronous proton-coupled electron transfer

Abstract

2-fluorenyl benzoates were recently shown to undergo C–H bond oxidation through intramolecular proton transfer coupled with electron transfer to an external oxidant. Kinetic analysis revealed unusual rate-driving force relationships. Our...

Reconciling Imbalanced Transition State Effects with Nonadiabatic CPET Reactions

“…Even in cases with very small |η|, ΔG °PT and ΔG °ET have significant influences on reactivity via their correlations with DepthD−,AH+ and DepthDH+,A-. Furthermore, while the influence of ΔG°CPET on rate constants can be sensitive to the individual contributions of ΔG °PT and ΔG °ET' (or alternatively ΔG °ET and ΔG °PT'), 24,40 our results demonstrate that the offdiagonal free energies ΔG °PT and ΔG °ET influence rate constants independent of their contributions to ΔG °CPET. However, we acknowledge that experimentally disentangling these effects is challenging.…”

“…[33][34][35][36][37] A central paradox that has recently emerged is how the influence of off-diagonal thermodynamic elements, which is rooted in semiclassical transition state theory, can be reconciled with CPET reactions which are widely acknowledged to be nonclassical or nonadiabatic (Figure 1, right). 16,[38][39][40][41] The specific formulations for how ΔG °PT and ΔG °ET can affect CPET reactivity vary, but are commonly supported by DFT optimized transition states 9,24,27,28 and invoke textbook physical organic concepts such as nonperfect synchronization, imbalanced transition states, and More O'Ferral-Jencks diagrams. [42][43][44][45][46][47] However, the light mass of protons means that quantum effects such as tunneling are often important, and even dominant, in CPET reactivity.…”

“…It is unclear how to reconcile structure-activity relationships from semiclassical transition state theory with the significant quantum effects which can occur in proton transfer, or if such a reconciliation is even feasible. 16,24,[38][39][40]60,61 While this dilemma has been explicitly raised in the context of CPET reactions, it may apply to any imbalanced or asynchronous reactivity with a proton transfer component.…”

Structural and Thermodynamic Effects on the Kinetics of C–H Oxidation by Multisite Proton-Coupled Electron Transfer in Fluorenyl Benzoates

“…The many examples of MS-PCET cleavage of O–H and N–H bonds are thought to rely on hydrogen bonding to bring the base into the appropriate position, but C–H bonds do not engage in strong hydrogen bonds. The 2-fluorenyl benzoate motifs depicted in Figure A undergo oxidative cleavage of the fluorenyl C–H bond by the MS-PCET mechanism, with electron transfer (ET) to an outer-sphere oxidant concerted with intramolecular proton transfer (PT) to the appended benzoate group. ,, The importance of accessing this new mechanism for C–H activation is highlighted by the recent emergence of powerful synthetic procedures for the MS-PCET activation of polar X–H bonds and, more recently, C–H bonds. , …”

H-atom Abstraction Reactivity through the Lens of Asynchronicity and Frustration with their Counter-Acting Effects on Barriers

“…11,12,13 The paramount role of HAA reactions in chemistry has also inspired numerous theoretical efforts to unveil the physical underpinnings of the process and their influence on reaction rates, 14,15,16 and to distinguish the mechanistic nuances of HAA. 17,18,19 Despite these advances, the design of synthetic methodologies leveraging selective HAA remains a heuristic process, 20,21 and theory is usually invoked a posteriori to rationalize experimental outcomes. 22,23 This gap between theory and experiment diagnoses the urge for a physicochemical framework allowing the prediction of HAA free energy barriers from experimentally and/or computationally accessible quantities, a yet unsolved problem due to the intrinsic complexity of HAA reactions.…”