Chemoselective Synthesis of 1,5-Benzodi(thi)azepine Derivatives from 1‑Polyfluoroalkyl-3-styryl-1,3-diketones

Chemoselective methods for the synthesis of 1,5-benzodiazepine derivatives have been developed from 1-polyfluoroalkyl-3-styryl-1,3-diketones and o-arylenediamines or 2-aminothiophenol. When the reaction was carried out in MeOH or MeCN at room temperature, 2,3,4,5-tetrahydro-1H-1,5-benzodiazepines were obtained in 36-90% yields as a result of the addition of 1,2-diamine to the α,β-unsaturated ketone fragment of the enedione. A similar reaction of 1-CF₃-3-styryl-1,3-diketones in MeOH at -18 °C led to 2-hydroxy-4-styryl-2,3-dihydro-1H-1,5-benzodiazepines in 57-87% yields as a result of the addition of 1,2-diamine to the 1,3-dicarbonyl fragment of the enedione. Dehydration of 2-hydroxy-4-styryl-2,3-dihydro-1H-1,5-benzodiazepines with trifluoroacetic acid in CH₂Cl₂ at room temperature gave the corresponding 3H-1,5-benzodiazepines in 73-96% yields. 2-Difluoromethyl-substituted 3H-1,5-benzodiazepines can be synthesized directly from the corresponding enediones and o-arylenediamines in MeOH at room temperature in one step in 76-95% yields. 2-Aminothiophenol reacts with 1-polyfluorolalkyl-3-styryl-1,3-diketones at reflux in EtOH to form 2,3,4,5-tetrahydro-1,5-benzothiazepines in 24-36% yields, whereas the reaction with aminophenol stops at the enaminone stage.