The Importance of Kinetic and Thermodynamic Control when Assessing Mechanisms of Carboxylate-Assisted C-H Activation

Raed A. Alharis, Claire L. McMullin, David L. Davies*, Kuldip Singh, Stuart A. Macgregor

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


The reactions of substituted 1-phenylpyrazoles (phpyz-H) at [MCl2Cp]2 dimers (M = Rh, Ir; Cp∗ = C5Me5) in the presence of NaOAc to form cyclometalated Cp∗M(phpyz)Cl were studied experimentally and with density functional theory (DFT) calculations. At room temperature, time-course and H/D exchange experiments indicate that product formation can be reversible or irreversible depending on the metal, the substituents, and the reaction conditions. Competition experiments with both para- and meta-substituted ligands show that the kinetic selectivity favors electron-donating substituents and correlates well with the Hammett parameter giving a negative slope consistent with a cationic transition state. However, surprisingly, the thermodynamic selectivity is completely opposite, with substrates with electron-withdrawing groups being favored. These trends are reproduced with DFT calculations that show C-H activation proceeds by an AMLA/CMD mechanism. H/D exchange experiments with the meta-substituted ligands show ortho-C-H activation to be surprising facile, although (with the exception of F substituents) this does not generally lead to ortho-cyclometalated products. Calculations suggest that this can be attributed to the difficulty of HOAc loss after the C-H activation step due to steric effects in the 16e intermediate that would be formed. Our study highlights that the use of substituent effects to assign the mechanism of C-H activation in either stoichiometric or catalytic reactions may be misleading, unless the energetics of the C-H cleavage step and any subsequent reactions are properly taken into account. The broader implications of our study for the assignment of C-H activation mechanisms are discussed.

Original languageEnglish
Pages (from-to)8896-8906
Number of pages11
JournalJournal of the American Chemical Society
Issue number22
Publication statusPublished - 5 Jun 2019


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