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

• Published in: iScience 2023-01, Vol.26 (1), p.105790-105790, Article 105790
• Main Authors: Beckers, Igor, De Vos, Dirk
• Format: Article
• Language: English
• Subjects: Catalysis; Chemistry; Organic chemistry
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2022.105790

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. [Display omitted] •Catalytic C-H arylation reaction studied via kinetic and computational modeling•C-H activation and oxidative addition identified as rate-determining steps•Rational modification of the ligand maximizes catalytic turnover Catalysis; Chemistry; Organic chemistry