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Direct Access to Trifluoromethylated Benzo[d]oxepines from o-Alkynylaryl Aldehydes and Trifluorodiazoethane

Anamika Dhami, Sanoop P. Chandrasekharan and Kishor Mohanan*

*Medicinal and Process Chemistry Division, Central Drug Research Institute (CSIR), Sitapur Road, P.O. Box 173, Lucknow, Uttar Pradesh 226031, India, Email: kishor.mohanancdri.res.in

A. Dhami, S. P. Chandrasekharan, K. Mohanan, Org. Lett., 2023, 25, 3018-3022.

DOI: 10.1021/acs.orglett.3c00801



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Abstract

A silver-catalyzed reaction between o-alkynylaryl aldehydes and trifluorodiazoethane provides 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, followed by a ring-expansive addition of trifluorodiazoethane.


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proposed mechanism



General procedure for the synthesis of trifluoromethylated benzo[d]oxepines

To an oven-dried round bottom flask charged with ortho-alkynylarylaldehyde (0.40 mmol), and silver trifluoromethanesulfonate (0.08 mmol) was added 2 mL of toluene, and the reaction mixture was stirred at 60 C followed by the slow addition of trifluorodiazoethane (stock solution in toluene, 0.80 mmol). The reaction mixture was stirred at 60 C for 2 h. After the completion of the reaction, as indicated by TLC, the solvent was evaporated, and the crude reaction mixture was extracted using ethyl acetate (15 3 mL) and water (15 mL). The organic layer was washed with brine, dried over anhydrous Na2SO4, and evaporated under reduced pressure. The residue was purified using column chromatography (100-200 mesh silica gel) using ethyl acetate/hexane as the eluent to afford product.


Key Words

benzo-fused O-heterocycles


ID: J54-Y2023