A facile synthetic route to 2-trifluoromethyl-substituted polyfunctionalized chromenes and chromones

A method for the preparation of methyl 4-hydroxy-2-(trifluoromethyl)-4H-chromenes-3-carboxylate derivatives 3a–j from readily available trifluoromethylated building block methyl (Z)-2-bromo-4,4,4-trifluoro-2-butenoate 1 was described. Treatment of 3a–j with Sarrett reagent in CH2Cl2 generated methyl 4-oxo-2-(trifluoromethyl)-chromene-3-carboxylate derivatives 4a–h with moderate to good yields, which can be converted to 2-trifluoromethyl-substituted multifunctional benzoxepins through cyclopropanation and Lewis acid-catalyzed ring opening.

Reaction of salicylaldehydes with a novel building block-methyl (Z)-2-bromo-4,4,4-trifluoro-2-butenoate 1 in the presence of excess Et3N under mild conditions gave methyl 4-hydroxy-2-(trifluoromethyl)-4H-chromenes-3-carboxylate derivatives 3a–j in high yields. Treatment of 3a–j with Sarrett reagent in CH2Cl2 gave methyl 4-oxo-2-(trifluoromethyl)-chromene-3-carboxylate derivatives 4a–h with moderate to good yields.Figure optionsDownload as PowerPoint slideHighlights
► New application of trifluoromethylated building block methyl (Z)-2-bromo-4,4,4-trifluoro-2-butenoate.
► Easy access to trifluoromethylated chromenes and chromones.
► Trifluoromethylated medium-size ring formation through cyclopropanation and ring opening.