Ligand Design Enables Cu-Catalyzed Etherification of Aryl Bromides Using Mild Bases
Name
ligand-design-enables-cu-catalyzed-etherification-of-aryl-bromides-using-mild-bases.pdf
Description
Published version
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3.06 MB
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Adobe PDF
Checksum (MD5)
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Author(s)
Strauss, Michael J
Greaves, Megan E
Kim, Seoung-Tae
Schmidt, Michael A
Scola, Paul M
Buchwald, Stephen L
Date Issued
January 5, 2026
Journal
Organic Letters
Publisher
American Chemical Society
Citation
Ligand Design Enables Cu-Catalyzed Etherification of Aryl Bromides Using Mild Bases
Michael J. Strauss, Megan E. Greaves, Seoung-Tae Kim, Michael A. Schmidt, Paul M. Scola, and Stephen L. Buchwald. Organic Letters 2026 28 (2), 855-859.
Version
Final published version
Abstract
We report a Cu-catalyzed method for the efficient coupling of base-sensitive aryl bromides and alcohols utilizing a newly developed N1,N2-diarylbenzene-1,2-diamine ligand, L15. This ligand was developed to increase the Lewis acidity of the Cu center, thereby permitting the use of a substantially milder base (NaOTMS or NaOPh) relative to those required in a previous iteration of this methodology (NaOMe or NaOt-Bu). Under the optimized reaction conditions, several classes of previously incompatible aryl bromides were efficiently transformed, including base-sensitive heterocycles and those containing acidic functional groups. Kinetic analyses support that C–O coupling proceeds via a mechanism involving binding/deprotonation of alcohol nucleophiles, that the pKa of the base influences the overall rate law, and that substoichiometric quantities of strong base can be utilized to accelerate ligand activation and thereby increase the overall rate of the transformation.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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Creative Commons Attribution-NonCommercial-NoDerivatives
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DOI of Published Version
10.1021/acs.orglett.5c05127
