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Updated: Aug 1, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Direct Access to Trifluoromethylated Benzo[d]oxepines from o-Alkynylaryl Aldehydes and Trifluorodiazoethane
Anamika Dhami1, Sanoop P Chandrasekharan1, Kishor Mohanan1,2
1Medicinal and Process Chemistry Division, Central Drug Research Institute (CSIR), BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, P.O. Box 173, Lucknow, Uttar Pradesh 226031, India.
Abstract:
Reported in this Letter is a silver-catalyzed reaction between o-alkynylaryl aldehydes and trifluorodiazoethane that enables an expedient synthesis of trifluoromethylated benzo[d]oxepines. The reaction works through a silver-promoted 6-endo-dig cyclization of o-alkynylbenzaldehydes for the generation of an isochromenylium intermediate, which upon a ring-expansive addition of trifluorodiazoethane delivers a novel class of trifluoromethylated benzoxepine frameworks. This strategy was applied to the synthesis of phosphonylated benzo[d]oxepines using the Seyferth-Gilbert reagent.
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