Condition-Controlled Selective Synthesis of CF3-Chromene and CF3-Benzofuran from N-Phenoxyacetamide and CF3-Ynone

Presented herein is a condition-controlled selective synthesis of CF₃-chromene and CF₃-benzofuran based on the reaction of N-phenoxyacetamide and CF₃-ynone. When the reaction is carried out in MeOH under the catalysis of Rh(III), CF₃-chromene is formed via C—H metalation-initiated alkenylation, acetamide group migration and intramolecular oxo-nucleophilic addition. On the other hand, when the reaction is run in DMSO under the promotion of CsOAc, CF₃-benzofuran is generated via aza-Michael addition-initiated [3,3]-σ rearrangement, intramolecular oxo-nucleophilic addition and water elimination. To our knowledge, this is the first report on the selective construction of chromene or benzofuran scaffold along with introduction of a CF₃ unit from the same starting materials. The methodology was scalable and the products could be readily transformed into other valuable products. Moreover, the products thus obtained possess decent anticancer activity.