Domino [3+2] Cycloaddition/Annulation Reactions of β‐(2‐Aminophenyl)‐α,β‐ynones with Nitrile Oxides: Synthesis of Isoxazolo[4,5‐c]quinolines

Abstract

β‐(2‐Aminophenyl)‐α,β‐ynones react with nitrile oxides by domino [3+2] cycloaddition/annulation reactions giving rise to isoxazolo[4,5‐c]quinolines in satisfactory yields. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Sequential 1,3‐Dipolar Cycloaddition of Nitrones to β‐(2‐Aminophenyl) α,β‐Ynones and Cyclocondensation: A New Entry to the Isoxazolino[4,5‐c]quinoline Ring

“…According to our previous studies, [1][2][3][4][5] the present process can be explained as depicted in Scheme 3: regioselective 1,3-dipolar cycloaddition of nitrones 2 to α,β-ynones 1 results in the formation of alkenes 5, from which the quinoline nucleus is generated by condensation between the amino and carbonyl groups.…”

“…[2,3] Moreover, we reported that sequential [2+2] cycloaddition of cycloalkanone enamines with 1 followed by cyclocondensation afforded quinolines cis-fused to different-sized carbocyclic rings. [4] In a related process, the reactions of 1 with azides [1] or nitrile oxides [5] resulted in the formation of quinoline derivatives cis-fused to heteroaromatic triazole or isoxazole rings. These synthetic methods can lead to the formation of polycyclic quinolines that are not otherwise easily available.…”

“…[11] On the other hand, the polycyclic quinoline ring system is also present in pharmacologically active substances. [5,12,13] Although there are various efficient procedures leading to isoxazolines, to the best of our knowledge the synthesis of isoxazolino [4,5-c]quinolines 4 has not been reported yet; only dehydrogenated analogues of 4, namely isoxazolo [4,5-c]quinolines, have been synthesized. [5,[14][15][16] Consequently, we focused our efforts on the development of a viable approach to the synthesis of 4.…”

A General Approach to the Synthesis of Substituted Isoxazolo[4,3‐c]quinolines via Chalcones

“…[13][14][15] During the program we became interested in the synthesis of isoxazolo [4,3-c]quinolines. A literature survey revealed that, although there exist a number of strategies for the synthesis of isoxazolo [4,5-c]quinolines, [16][17][18][19] only two reports [20][21] of the synthesis of isoxazolo [4,3-c]quinolines exist, despite their significance as structural components of MRP-1 inhibitors. [22,23] Initially we reasoned that such an architecture could be generated from 3-(2-nitrophenyl)isoxazole-4-carboxylate by reduction of the nitro group to an amino group and subsequent cyclization with the carboxylate or formyl function.…”

“…In principle, the reduction of the nitro group would result in a 2-aminophenyl derivative, in which the amino group should readily undergo intramolecular cyclization with the keto moiety of the benzoyl group to furnish isoxazolo [3,4-c]quinoline. The rationale for such a strategy was based on reports by Rossi et al [16] on the synthesis of isoxazolo [4,5-c]quinolines from β-(2-aminophenyl)-α,β-ynones and Kaye et al…”