Bidentate NHC-Containing Ligands for Copper Catalyzed Synthesis of Functionalized Diaryl Ethers with Low Catalyst Loading
DOI: 10.14469/hpc/12829 Metadata
Created: 2023-07-12 10:13
Last modified: 2024-11-27 16:55
License: Creative Commons: Public Domain Dedication 1.0
Funding: (none given)
Co-author: Henry Rzepa Co-author: James A. Bull Co-author: Andrew White Co-author: Frederick Goldberg Co-author: Henry Rzepa Co-author: Luis Casarrubios
Description
Data for new compoundDiaryl and heteroaryl ethers are important and common motifs in drug discovery and agrochemicals. Here we present a catalytic system for the copper catalysed arylation of phenols with aryl halides. Bidentate N-heterocyclic carbene ligands provide a well-defined catalytic system that enable low loading of copper in effective coupling reactions (0.5 mol% Cu or lower). The reaction scope of aryl iodides and aryl bromides is developed, that is tolerant of functional groups and a library of biaryl ethers with lead-like properties is prepared. The presence of excess ligand (in a 1:3 ratio) is shown to be optimal to prevent catalyst degradation, presumably by avoiding decomplexation of the ligand. This is also supported by the catalytic results obtained with pre-formed copper complexes. The kinetics of the reaction are examined and shown to be first order in copper, supportive of a well-defined catalyst species, first order in phenol and aryl iodide, and zero order in base under the developed conditions. Computational studies performed using Minnesota MN15-L parametrisation method support an oxidative addition-reductive elimination pathway. Reductive elimination would be turnover limiting and occur through an intimate ion pair intermediate.
Members
| DOI | Description |
|---|---|
| 10.14469/hpc/12832 | Diaryl ethers - NMR Data |
| 10.14469/hpc/12846 | NHC salts and metal complexes - NMR Data |
| 10.14469/hpc/12929 | Bidentate NHC-Containing Ligands for Copper Catalyzed Synthesis of Functionalized Diaryl Ethers with Low Catalyst Loading. Computational modelling |
| 10.14469/hpc/12918 | [M(NHC)] Metal Complexes - Crystallography Data |
Associated DOIs
| Current dataset ... | DOI | Description |
|---|---|---|
| References | 10.1002/adsc.202400909 | Published article |