Combined Kinetic and Computational Analysis of the Palladium-Catalyzed Formylation of Aryl Bromides
Year: 2024
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide Aryl aldehydes are key synthetic intermediates in the manufacturing of active pharmaceutical ingredients. They are generated on scale (>1000 kg) through the palladium-catalyzed formylation of aryl bromides using syngas (CO/H 2 ). The best-in-class catalyst system for this reaction employs di-1-adamantyl- n -butylphosphine (cata CX ium A), palladium(II) acetate, and tetramethylethylenediamine. Despite nearly 20 years since its initial report, a mechanistic understanding of this system remains incomplete. Here, we use automation, kinetic analysis, and DFT calculations to develop a mechanistic model for this best-in-class catalyst. We suggest that a combination of the migratory insertion step and dihydrogen activation step is likely involved in the turnover-limiting sequence. The reaction kinetics are responsive to the nature of the substrate, with electron-rich aryl bromides reacting faster and more selectively than their electron-poor counterparts due to the influence of electronics in the migratory insertion step. Our findings add additional insight into the proposed mechanism of palladium-catalyzed formylation of aryl bromides.
Source: ACS Catalysis
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
OpenAlex ID: W4405508167