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

J Org Chem. 2022 Mar 4;87(5):2997-3006. doi: 10.1021/acs.joc.1c02834. Epub 2022 Feb 3.

Abstract

Our recent experimental and theoretical investigations have shown that fluorene C-H bonds can be activated through a mechanism in which the proton and electron are transferred from the C-H bond to a separate base and oxidant in a concerted, elementary step. This multisite proton-coupled electron transfer (MS-PCET) mechanism for C-H bond activation was shown to be facilitated by shorter proton donor-acceptor distances. With the goal of intentionally modulating this donor-acceptor distance, we have now studied C-H MS-PCET in the 3-methyl-substituted fluorenyl benzoate (2-Flr-3-Me-BzO-). This derivative was readily oxidized by ferrocenium oxidants by initial C-H MS-PCET, with rate constants that were 6-21 times larger than those for 2-Flr-BzO- with the same oxidants. Structural comparisons by X-ray crystallography and by computations showed that addition of the 3-methyl group caused the expected steric compression; however, the relevant C···O- proton donor-acceptor distance was longer, due to a twist of the carboxylate group. The structural changes induced by the 3-Me group increased the basicity of the carboxylate, weakened the C-H bond, and reduced the reorganization energy for C-H bond cleavage. Thus, the rate enhancement for 2-Flr-3-Me-BzO- was due to effects on the thermochemistry and kinetic barrier, rather than from compression of the C···O- proton donor-acceptor distance. These results highlight both the challenges of controlling molecules on the 0.1 Å length scale and the variety of parameters that affect PCET rate constants.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Benzoates / chemistry
  • Carboxylic Acids / chemistry
  • Electron Transport
  • Electrons*
  • Kinetics
  • Oxidants / chemistry
  • Protons*
  • Thermodynamics

Substances

  • Benzoates
  • Carboxylic Acids
  • Oxidants
  • Protons