Intramolecular inverse-electron-demand Diels-Alder reactions of imidazoles with 1,2,4-triazines: a new route to 1,2,3,4-tetrahydro-1,5-naphthyridines and related heterocycles.
The intramolecular inverse-electron-demand Diels-Alder reaction between imidazoles and 1,2,4-triazines linked by a trimethylene tether from the imidazole N1 position to the triazine C3 proceed in excellent yields to produce 1,2,3,4-tetrahydro-1,5-naphthyridines. The reaction proceeds by a cycloaddition with subsequent loss of nitrogen, followed by a presumed stepwise loss of a nitrile. The analogous intramolecular cycloadditions employing a tetramethylene tether also proceeded to give 2,3,4,5-tetrahydro-1H-pyrido[3,2-b]azepines in acceptable yields. The reaction to produce the tetrahydro-1,5-naphthyridines can also be promoted with microwave irradiation.
Department of Chemistry and Center for Chemical Methodology and Library Development, Boston University, 590 Commonwealth Avenue, Boston, Massachusetts 02215, USA.
Brian R
BR
Lahue
Sie-Mun
SM
Lo
Zhao-Kui
ZK
Wan
Grace H C
GH
Woo
John K
JK
Snyder
D003500:Cyclization; D004583:Electrons; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D009287:Naphthyridines / Q000138:chemical synthesis*; D014227:Triazines / Q000737:chemistry*
D006571:Heterocyclic Compounds; D007093:Imidazoles; D009287:Naphthyridines; D014227:Triazines; C093444:1,2,4-triazine