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Updated: Mar 1, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Base-catalyzed diastereoselective trimerization of trifluoroacetone
Anthony P Silvestri1, Philip E Dawson1
1Department of Chemistry, The Scripps Research Institute (TSRI), 10550 North Torrey Pines Road, La Jolla, California 92037, USA. dawson@scripps.edu.
Abstract:
Amphiphilic fluorocarbons have unique properties that facilitate their self assembly and adhesion to both inorganic and biological substrates. Incorporation of these moieties into valuable constructs typically require complex synthetic routes that have limited their use. Here, the base-catalyzed diastereoselective synthesis of 6-methyl-2,4,6-tris(trifluoromethyl)tetrahydro-2H-pyran-2,4-diol is reported. Trimerization of trifluoroacetone in the presence of 5 mol% KHMDS delivers one of four diastereomers selectively in 81% yield with no column chromatography. Temperature screening revealed the reversibility of this trimerization and the funneling of material into the most thermodynamically stable oxane. Subsequent functionalization with boronic acids is reported.
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