Modular Synthesis of Highly Substituted Pyridines via Enolate α-Alkenylation.

Journal article

A novel methodology for the synthesis of highly substituted pyridines based on the palladium-catalyzed enolate α-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 β-haloalkenylaldehyde participates in α-alkenylation with a ketone to afford a 1,5-dicarbonyl surrogate, which then undergoes cyclization/double elimination to the corresponding pyridine product, all in one pot. The β-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.

Authors: Hardegger, L; Habegger, J; Donohoe, T

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: American Chemical Society
• Journal: Organic letters
• Volume: 17
• Issue: 13
• Pages: 3222–3225
• Publication date: 2015-06-01
• DOI: 10.1021/acs.orglett.5b01312
• EISSN: 1523-7052
• ISSN: 1523-7060
• Language: English