Microwave-Assisted, Rhodium(III)-Catalyzed N-Annulation Reactions of Aryl and α,β-Unsaturated Ketones with Alkynes

• Published in: Chemistry : a European journal 2014-01, Vol.20 (1), p.323-333
• Main Authors: Lee, Hyejeong, Sim, Yong-Kyun, Park, Jung-Woo, Jun, Chul-Ho
• Format: Article
• Language: English
• Subjects: alkynes; annulation; CH activation; heterocycles; ketones
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201302699

New RhIII‐catalyzed, one‐pot N‐annulation reactions of aryl and α,β‐unsaturated ketones with alkynes in the presence of ammonium acetate have been developed. Under microwave irradiation conditions, the processes lead to rapid formation of the respective isoquinoline and pyridine derivatives with efficiencies that are strongly dependent on the steric nature of the aryl ring and enone substituents. By employing this protocol, a variety of isoquinoline and pyridine derivatives were prepared in high yields. In addition, a new one‐pot approach to the synthesis of pyridines, involving four‐component reactions of ketones, formaldehyde, NH4OAc, and alkynes, has been uncovered. This process takes place through a route involving initial aldol condensation of the ketone with formaldehyde to generate a branched α,β‐unsaturated ketone that then undergoes RhIII‐catalyzed N‐annulation with NH4OAc and the alkyne. Ring road: One‐pot N‐annulation reactions of aryl and α,β‐unsaturated ketones with alkynes in the presence of NH4OAc under microwave (MW) irradiation conditions have been developed (see scheme). These processes lead to the rapid formation of the respective isoquinoline and pyridine derivatives. In addition, an approach for the synthesis of pyridines that involves four‐component reactions is presented.