Copper(II)-Catalyzed Ether Synthesis from Aliphatic Alcohols and Potassium Organotrifluoroborate Salts
Tan D. Quach and Robert A. Batey*
*Davenport Research Laboratories, Department of Chemistry, University of
Toronto, 80 St. George Street, Toronto, Ontario M5S 3H6, Canada, Email:
rbateychem.utoronto.ca
T. D. Quach, R. A. Batey, Org. Lett., 2003, 5, 1381-1384.
DOI: 10.1021/ol034454n
Abstract
A protocol for the copper(II)-catalyzed etherification of aliphatic primary and secondary alcohols and phenols with air- and moisture-stable potassium alkenyl- and aryltrifluoroborate salts utilizes a catalytic amount of copper(II) acetate with 4-(dimethylamino)pyridine as ligand in presence of 4 Å molecular sieves under an atmosphere of oxygen.
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Details
The document describes a protocol for copper(II)-catalyzed etherification of aliphatic alcohols using potassium organotrifluoroborate salts under mild and neutral conditions. This method allows for the cross-coupling of aliphatic primary and secondary alcohols and phenols with air- and moisture-stable potassium alkenyl- and aryltrifluoroborate salts. The optimized conditions involve using catalytic copper(II) acetate with 4-(dimethylamino)pyridine as a ligand and 4 Å molecular sieves under an oxygen atmosphere. This approach offers an alternative to traditional Pd- and Cu-catalyzed etherifications, which often require harsher conditions and expensive catalysts. The protocol is effective for a variety of alcohols, including phenols, aliphatic, allylic, and internal propargylic alcohols, and tolerates various functional groups. However, it is sensitive to steric effects around the hydroxyl group, and tertiary alcohols do not undergo cross-coupling. The method also works with arylboronic acids, though yields are lower due to their higher propensity for Cu-promoted oxidation. The study highlights the potential of this protocol for complex molecule synthesis and parallel synthesis applications. The research was supported by NSERC, ORDCF, and Merck-Frosst, with additional funding for the authors from various scholarships and awards.
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ID: J54-Y2003-420