Studies toward the enantioselective total synthesis of (+)-corydaline

Considering the versatility of benzyne and derivatives in organic chemistry, with applications in total syntheses and preparations of functional materials, we intend to accomplish the enantioselective total synthesis of protoberberine alkaloid named (+)-corydaline employing as key steps a tandem transformation triggered by aryne formation and a ruthenium(II)-catalyzed enantioselective hydrogenation. Thus, we started the synthesis of (+)-corydaline through preparations of an isoquinolinedione and a 2-(trimethylsilyl)aryl triflate. Afterwards, the heterocyclic intermediate obtained was allowed to react with the aromatic triflate through a tandem process involving aryne formation, nucleophilic addition, intramolecular cyclization, and CO extrusion, affording the alkaloid named yuanamide in 74% yield. Yuanamide was subjected to reductions with LiAlH4 and NaBH3CN leading to (±)-corydaline in 42% yield. In order to complete the asymmetric total synthesis, we expect to reduce yuanamide using ruthenium(II)-catalyzed enantioselective hydrogenation followed by reaction with LiAlH4 to achieve (+)-corydaline.