Cyclocondensation of 2‑(α-Diazoacyl)‑2H‑azirines with Amidines in Diazo Synthesis of Functionalized Naphtho[1,2‑d]imidazoles

• Published in: Journal of organic chemistry 2024-06, Vol.89 (12), p.8641-8655
• Main Authors: Zanakhov, Timur O., Galenko, Ekaterina E., Novikov, Mikhail S., Khlebnikov, Alexander F.
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.4c00598

A diazo approach toward functionalized naphtho­[1,2-d]­imidazole derivatives has been developed. It involved a new reaction of arylamidines with 2-(α-diazoacyl)-2H-azirines giving 5-aryl-4-(α-diazoacyl)-1H-imidazoles under mild conditions in good yields. The mechanism of annulation of azirines with amidines is discussed based on DFT calculations. The reaction proceeds in an unusual manner by cleavage of the azirine C–C bond, allowing for the transfer of the aryl substituent from the arylamidine to the proper position of the key intermediate of naphtho­[1,2-d]­imidazole synthesis. Under thermolysis conditions, 5-aryl-4-(α-diazoacyl)-1H-imidazoles undergo Wolff rearrangement followed by the selective 6π-cyclization of transient ketene to form 3H-naphtho­[1,2-d]­imidazoles bearing various substituents in the positions 2,3,4,5,7,8,9. Additionally, variation of the substituents at position 5 of naphtho­[1,2-d]­imidazoles is possible through the formation of triflates and subsequent cross-coupling reactions. One more heterocyclic pharmacophoric skeleton, 3H-furo­[3′,2’:3,4]­naphtho­[1,2-d]­imidazole, was easily constructed from methyl 5-hydroxy-3H-naphtho­[1,2-d]­imidazole-4-carboxylates in a one-pot mode using O-alkylation with phenacyl bromides followed by base-induced intramolecular acyl substitution at room temperature with high yields.