Rational ligand modification maximizes turnover rate in a model Pd-catalyzed C-H arylation

iScience. 2022 Dec 10;26(1):105790. doi: 10.1016/j.isci.2022.105790. eCollection 2023 Jan 20.


The direct cross-coupling of (hetero)aromatics without prior functionalization is a promising reaction for the chemical and pharmaceutical industries, enabling the conversion of inexpensive feedstocks in a highly step-efficient manner. However, many C-H arylations rely on high loadings of a Pd catalyst that preclude their use in low-cost applications. In this work, we have maximized the turnover rate of a Pd-catalyzed C-H arylation reaction through rational tuning of the ligands. Starting from a computational study of the catalytic mechanism, a kinetic model was derived that accurately explains the experimental time profiles. Quantitative structure-activity relationships between the substituents on the ligands and the resulting catalytic activity for various C-H arylations were obtained. This study demonstrates that, depending on the coupling partner, the C-H activation is not the sole rate-limiting step, and that the ligands can be adapted accordingly to further accelerate catalytic turnover.

PMID:36594021 | PMC:PMC9803853 | DOI:10.1016/j.isci.2022.105790


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