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Ligand Design Enables Cu-Catalyzed Etherification of Aryl Bromides Using Mild Bases
Michael J Strauss1, Megan E Greaves1, Seoung-Tae Kim1
1Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
Organic Letters
|January 6, 2026
Summary
A new copper-catalyzed coupling method uses a novel diamine ligand (L15) to efficiently join base-sensitive aryl bromides and alcohols with milder bases. This expands the scope of aryl bromide coupling reactions.
Area of Science:
- Organic Chemistry
- Catalysis
- Synthetic Methodology
Background:
- Copper-catalyzed cross-coupling reactions are vital in organic synthesis.
- Previous methods often required harsh bases, limiting substrate scope.
- Developing milder conditions is crucial for sensitive functional groups.
Purpose of the Study:
- To develop a novel copper-catalyzed method for coupling base-sensitive aryl bromides and alcohols.
- To introduce a new N1,N2-diarylbenzene-1,2-diamine ligand (L15) to enhance reaction efficiency.
- To enable the use of milder bases in aryl bromide coupling.
Main Methods:
- Utilized a newly developed N1,N2-diarylbenzene-1,2-diamine ligand (L15) in copper catalysis.
- Employed milder bases such as sodium trimethoxide (NaOTMS) or sodium phenoxide (NaOPh).
- Optimized reaction conditions for efficient C-O bond formation.
Main Results:
- Achieved efficient coupling of base-sensitive aryl bromides and alcohols.
- Successfully transformed previously incompatible substrates, including heterocycles and compounds with acidic groups.
- Demonstrated that milder bases (NaOTMS, NaOPh) are effective with the L15 ligand.
Conclusions:
- The developed Cu-catalyzed method with L15 ligand broadens the scope of C-O coupling reactions.
- The new methodology allows for the use of milder bases, preserving sensitive functional groups.
- Kinetic studies provided insights into the reaction mechanism and rate-determining steps.
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