Development and Molecular Understanding of a Pd-Catalyzed Cyanation of Aryl Boronic Acids Enabled by High-Throughput Experimentation and Data Analysis
Abstract
A synthetic method for the palladium-catalyzed cyanation of aryl boronic acids using bench stable and non-toxic N-cyanosuccinimide has been developed. High-throughput experimentation facilitated the screen of 90 different ligands and the resultant statistical data analysis identified that ligand sigma-donation, pi-acidity and sterics are key drivers that govern yield. Categorization into three ligand groups - monophosphines, bisphosphines and miscellaneous - was performed before the analysis. For the monophosphines, the yield of the reaction increases for strong sigma-donating, weak pi-accepting ligands, with flexible pendant substituents. For the bisphosphines, the yield predominantly correlates with ligand lability. The applicability of the designed reaction to a wider substrate scope was investigated, showing good functional group tolerance in particular with boronic acids bearing electron-withdrawing substituents. This work outlines the development of a novel reaction, coupled with a fast and efficient workflow to gain understanding of the optimal ligand properties for the design of improved palladium cross-coupling catalysts. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000515010Publication status
publishedExternal links
Journal / series
Helvetica Chimica ActaVolume
Pages / Article No.
Publisher
WileySubject
aryl boronic acids; cyanation; data analysis; high-throughput experimentation; ligand design; palladiumOrganisational unit
03363 - Togni, Antonio (emeritus) / Togni, Antonio (emeritus)
03872 - Copéret, Christophe / Copéret, Christophe
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