We report a mild palladium-catalyzed method for the selective allylation of 4-alkylpyridines in which highly basic pyridylic anions behave as soft nucleophiles.

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 βhydride 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.

We report a mild method for the synthesis of scaffolds bearing 4-pyridine and 4-piperidine moieties joined by a substituted methylene group. The method exploits the latent nucleophilicity of 4-alkylpyridines and the inherent electrophilicity of pyridines. 4-Alkylpyridines are transformed into nucleophilic alkylidene dihydropyridines (ADHPs) through a soft enolization approach using triethyl amine and chloroformate reagents. HCl is used to promote the addition of ADHPs to pyridine, yielding an adduct bearing pyridine and protected dihydropyridine fragments. Transfer hydrogenation delivers the desired compounds in good yields.