A Copper‐Catalyzed Decarboxylative Olefination Cascade Enables Access to Protoberberine Alkaloid Frameworks

We describe a streamlined one-pot strategy to construct highly functionalized protoberberine frameworks through a tandem Mannich/intramolecular acylation and copper-promoted decarboxylative olefination sequence. This operationally straightforward process delivers a wide array of derivatives in consistently high yields. Mechanistic investigations, including isolation of key intermediates, support a radical-driven decarboxylative olefination pathway that develops complex protoberberine-type alkaloids with exceptional efficiency. The utility of this synthetic platform is demonstrated through concise total syntheses of the neuroactive tetrahydroprotoberberine alkaloids (±)-isocorypalmine and (±)-stepholidine. Collectively, this chemistry establishes a concise and practical avenue for accessing valuable protoberberine scaffolds from readily available precursors.