Modular Synthesis of Highly Substituted Pyridines via Enolate α-Alkenylation

A, novel methodology for the synthesis of highly substituted pyridines based on the palladium-catalyzed enolate alpha-alkenylation of ketones is presented; the formation of aromatic compounds: is: a new direction for this catalytic C-C bond forming reaction. In the, key step, a protected beta-haloalkenylaldehyde participates in alpha-alkenylution with a ketone to afford a 1,5-dicarbonyl surrogate,, which then undergoes cyclitation/double elimination to the corresponding pyridine:product, all in one pot., The beta-haloalkenylaldehyde starting materials can be obtained from the corresponding methylene ketone via Vilsmeier haloformylation. Using this concise route, a variety, of highly substituted pyridines were synthesized in three steps from commercially available compounds.