Modular Pyridine Synthesis from Oximes and Enals through Synergistic Copper/Iminium Catalysis

• Published in: Journal of the American Chemical Society Vol. 135; no. 10; pp. 3756 - 3759
• Main Authors: Wei, Ye, Yoshikai, Naohiko
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 13-03-2013
• Subjects: Aldehydes - chemistry; Amines - chemistry; Catalysis; Copper - chemistry; Molecular Structure; Oximes - chemistry; Pyridines - chemical synthesis; Pyridines - chemistry; Quaternary Ammonium Compounds - chemistry
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja312346s

We describe here a [3+3]-type condensation reaction of O-acetyl ketoximes and α,β-unsaturated aldehydes that is synergistically catalyzed by a copper(I) salt and a secondary ammonium salt (or amine). This redox-neutral reaction allows modular synthesis of a variety of substituted pyridines under mild conditions with tolerance of a broad range of functional groups. The reaction is driven by a merger of iminium catalysis and redox activity of the copper catalyst, which would initially reduce the oxime N–O bond to generate a nucleophilic copper(II) enamide and later oxidize a dihydropyridine intermediate to the pyridine product.