A Ag2CO3/TFA-catalyzed intramolecular annulation approach to imidazo[1,2-c][1,3]oxazin-5-one derivatives?

Organic & Biomolecular Chemistry Pub Date: 2022-01-21 DOI: 10.1039/D1OB02352G

Abstract

A series of 2,7-disubstituted 3-methylimidazo[1,2-c][1,3]oxazin-5-ones were synthesized in good yields via Ag2CO3/TFA-mediated intramolecular annulation of N-Boc-2-alkynyl-4-bromo(alkynyl)-5-methylimidazoles. This methodology was carried out in the presence of a catalytic amount of silver carbonate and trifluoroacetic acid in dichloroethane at 60 °C. In all experiments, only the six-membered ring product was obtained since the possible five-membered compound was not observed, proving the high regioselectivity of this approach. A complementary computational study was performed in order to rationalize the mechanism of 6-endo-dig heterocycle formation. In addition, 2-bromo-3-methyl-7-phenylimidazo[1,2-c][1,3]oxazin-5-one was used as a building block to synthesize a small library of new 2-substituted imidazo[1,2-c][1,3]oxazin-5-one derivatives through the Suzuki, Sonogashira and Heck cross coupling reactions.

Graphical abstract: A Ag2CO3/TFA-catalyzed intramolecular annulation approach to imidazo[1,2-c][1,3]oxazin-5-one derivatives
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