Facile Access to Triazole-Fused 3,1-Benzoxazines Enabled by Metal-Free Base-Promoted Intramolecular C–O Coupling

Abstract

A convenient approach to assemble 1,2,3-triazole-fused 4H-3,1-benzoxazines has been developed. Diverse alcohol-tethered 5-iodotriazoles, readily accessible by a modified protocol for the Cu-catalyzed (3+2)-cycloaddition, were utilized as precursors of the target fused heterocycles. The intramolecular C–O coupling proceeded efficiently under base-mediated transition-metal-free conditions, furnishing cyclization products in yields up to 96%. Suppression of the competing reductive cleavage of the C–I bond was achieved by the use of Na2CO3 in acetonitrile at 100 °C. This practical and cost-effective procedure features a broad substrate scope and valuable functional group tolerance.

Divergent cyclization of 2-(5-iodo-1,2,3-triazolyl)benzamides toward triazole-fused lactams and cyclic imidates

“…As a part of our ongoing studies on the preparation and reactivity of triazoles, 21 we have developed a transition metal-free approach to fused triazoles based on intramolecular S N Ar-like substitution in nucleophile-tethered 5-iodotriazoles. This route proved to be successful (Scheme 1A-7 and B) for the preparation of various triazole-fused sultams, 22 3,1-benzoxazines, 23 benzoxazinones, 24 and benzoxazoles. 25 We hypothesized that the reaction with ambident nucleophiles such as anions of secondary amides 1 can be controlled to provide both triazole-containing quinazolinones 2 and benzoxazine-imines 3 (Scheme 2).…”