A Cascade Reaction of Michael Addition and Truce-Smiles Rearrangement to Synthesize Trisubstituted 4-Quinolone Derivatives

Abstract

A novel transition-metal-free cascade reaction to synthesize 4-quinolone derivatives has been demonstrated. Michael addition and Truce-Smiles rearrangement are included in this protocol, providing a broad scope of 4-quinolones in moderate-to-excellent yields. This work serves as an example of the use of sulfonamides through Truce−Smiles rearrangement to build heterocyclic compounds under mild conditions.

Recent advances in the synthesis of pharmaceutically active 4-quinolone and its analogues: a review

“…Similarly, Xie et al recently synthesized tri-substituted 4-quinolone derivatives 64 via a cascade reaction of Michael addition and Truce–Smiles rearrangement between benzene-sulfonamide derivatives 62 and 1-(2-bromophenyl)-3-phenyl prop-2-yn-1-ones 63 in the presence of K 2 CO 3 in DMF at 100 °C in excellent yield (Scheme 19). 30…”

1,2-Difunctionalizations of alkynes entailing concomitant C–C and C–N bond-forming carboamination reactions

“…A metal-free base-promoted intermolecular carboamination reaction of amides 141 with o -bromoaryl ketones 142 was exemplified by Ma and co-workers for the rapid construction of 4-quinoline moieties 143 ( Scheme 77 ). 92 Potassium carbonate was used as base in DMF as solvent. The reaction has indeed a very wide substrate scope.…”

Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common β-keto amide precursors

“…Considering the importance of 4-quinolones as potential drugs and biological probes, it is not surprising that the development of methods for their synthesis is a very active area of research. Recent contributions to the synthesis of 4-quinolones made use of phosphine-mediated redox cyclization of 1-(2-nitroaryl)prop-2-ynones [39], palladium-catalyzed carbonylative cyclization of 2-bromonitrobenzenes and alkynes [40], TsCl-mediated domino reaction of chromone-3-carboxaldehydes and amines [41], Pd-catalyzed redox-neutral C-N coupling reaction of iminoquinones with electron-deficient alkenes [42], NH 3 insertion into o-haloarylynones [43], gold(III)-catalyzed azide-yne cyclization [44], Michael/Truce-Smiles rearrangement cascade [45], and base-promoted annulations with isatoic anhydrides [46]. Many other contributions in this field up to 2019 have been extensively reviewed [47][48][49], with special attention to the total synthesis and functional analysis of 2-alkyl-4-quinolones as microbial signaling molecules [50,51].…”