Lewis Acid/Brønsted Base-Assisted Palladium Catalysis: Stereoselective Construction of Skeletally Diverse Spiro-Ketolactams from Vinylethylene Carbonates

The diversity of spirocyclic architecture offers a vast chemical space and enormous potential for drug discovery, while the skeletal diversity-oriented synthesis of spiromolecules from simple starting materials remains a challenging task. Here, we report a divergent stereoselective construction of [5,5] and [5,6] spiroheterocycles from identical substrates (vinylethylene carbonates and pyrrolidone-derived enones) through Lewis-acid-assisted and Brønsted-base-assisted palladium catalysis, respectively. With this protocol, a broad spectrum of enantioenriched tetrahydrofuranyl spiroketolactams was achieved via palladium/Al(OiPr)3 cocatalyzed asymmetric (3 + 2) annulations. A collection of cyclohexenyl spiroketolactams was synthesized through diastereoselective (4 + 2) annulations under a palladium/NaHCO3 catalytic system. Further synthesis elaboration was performed using both spiroskeletons to showcase the versatility of this methodology. In addition, density functional theory calculations provide a rationale toward the observed different reaction pathways with the divergently cooperative palladium catalysis.