Palladium-Catalyzed, Mild Dehydrogenation of 4-Alkylpyridines

We report a mild palladium-catalyzed selective dehydrogenation of 4-alkylpyridines that exploits their soft enolization to alkylidene dihydropyridines using allyl chloroformate under metal-free conditions. Treatment of these intermediates with a palladium catalyst liberates an alkylpyridylic anion and an allylpalladium(II) intermediate, which combine and undergo beta-hydride elimination to install a double bond. Importantly, the formation of gas byproducts makes the process very practical. Furthermore, the reaction tolerates a broad range of functional groups, including many that can be dehydrogenated using similar palladium-catalyzed reactions, and is selective for 4-alkylpyridines even in substrates bearing multiple pyridylic positions.

Automated summary

The mild palladium-catalyzed selective dehydrogenation of 4-alkylpyridines involves their soft enolization to generate alkylidene dihydropyridines using allyl chloroformate under metal-free conditions. The byproduct gas formation in the process makes it practical, and the reaction tolerates a broad range of functional groups while being selective for 4-alkylpyridines even in substrates with multiple pyridylic positions.