Room-Temperature Copper-Catalyzed Etherification of Aryl Bromides
Michael J Strauss1, Megan E Greaves1, Seoung-Tae Kim1
1Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02139, United States of America.
Angewandte Chemie (International Ed. in English)
|February 15, 2024
Summary
A new copper-catalyzed method enables efficient C-O coupling reactions at room temperature using a novel N¹,N²-diarylbenzene-1,2-diamine ligand (L8). This catalyst offers enhanced activity and a distinct mechanism, overcoming previous limitations in C-O bond formation.
Area of Science:
- Organic Chemistry
- Catalysis
- Synthetic Methodology
Background:
- Copper-catalyzed cross-coupling reactions are vital in organic synthesis.
- Existing C-O coupling methods face limitations, particularly with challenging substrates.
- Development of novel ligands is crucial for enhancing catalytic efficiency and scope.
Purpose of the Study:
- To develop a novel copper-catalyzed C-O coupling method.
- To introduce and evaluate a new N¹,N²-diarylbenzene-1,2-diamine ligand (L8).
- To investigate the mechanism and scope of the new catalytic system.
Main Methods:
- Copper-catalyzed cross-coupling reactions.
- Utilized a new N¹,N²-diarylbenzene-1,2-diamine ligand (L8) with copper.
- Investigated reaction conditions, substrate scope, and mechanistic pathways.
Main Results:
- Efficient C-O coupling of diverse aryl/heteroaryl bromides with alcohols at room temperature.
- The L8-based catalyst showed enhanced activity, coupling aryl bromides with acidic functional groups.
- Mechanistic studies revealed rate-limiting alkoxide transmetallation, distinct from other systems, leading to a 7-fold rate increase.
Conclusions:
- The developed Cu-catalyzed C-O coupling method using L8 overcomes limitations of previous approaches.
- The new ligand L8 demonstrates superior performance and a unique mechanistic pathway.
- The L8 ligand is anticipated to be valuable for other copper-catalyzed C-heteroatom bond-forming reactions.
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