Skeleton-Reorganizing Coupling Reactions of Cycloheptatriene and Cycloalkenones with Amines

Skeletal reorganization reactions have emerged as an intriguing tool for converting readily available compounds into complicated molecules inaccessible by traditional methods. Herein, we report a unique skeleton-reorganizing coupling reaction of cycloheptatriene and cycloalkenones with amines. In the presence of Rh/acid catalysis, cycloheptatriene can selectively couple with anilines to deliver fused 1,2-dihydroquinoline products. Mechanistic studies indicate that the retro-Mannich type ring-opening and subsequent intramolecular Povarov reaction account for the ring reorganization. Our mechanistic studies also revealed that skeleton-reorganizing amination between anilines and cycloalkenones can be achieved with acid. The synthetic utilization of this skeleton-reorganizing coupling reaction was showcased with a gram-scale reaction, synthetic derivatizations, and the late-stage modification of commercial drugs.

Automated summary

This study demonstrates a unique skeleton-reorganizing coupling reaction of cycloheptatriene and cycloalkenones with amines. The reaction selectively couples cycloheptatriene with anilines to deliver fused 1,2-dihydroquinoline products in the presence of Rh/acid catalysis. Mechanistic studies reveal that the ring reorganization occurs through retro-Mannich type ring-opening and subsequent intramolecular Povarov reaction. The synthetic utilization of this reaction is showcased with gram-scale reaction, synthetic derivatizations, and late-stage modification of commercial drugs.