Pd(II)-Catalyzed Site-Selective [2 + 2 + 1] Spiroannulation of 2-Pyridone with Alkyne

Spiropiperidine, an important pharmacophore, is widely found in many drugs and bioactive molecules. Despite the progress these methods have made in the diversity-oriented synthesis of spiropiperidine, site-selective spiroannulation remains a significant challenge. Herein, we report a novel and previously unexplored Pd(II)-catalyzed spiroannulation that uses readily available 2-pyridone as a precursor for piperidine to react with alkyne, undergoing site-selective [2 + 2 + 1] spiroannulation through direct vinylic C-H activation and two metallization steps, efficiently producing 3-spiropiperidine derivatives. This protocol offers a broad substrate scope, strong atom economy, and notable site selectivity and will quickly provide a platform for the diversity-oriented synthesis of 3-spiropiperidine derivatives through the site-selective spiroannulation of conjugated diene.