Cu‐Catalyzed Coupling of O‐Acyl Oximes with Isatins: Domino Rearrangement Strategy for Direct Access to Quinoline‐4‐Carboxamides by C–N Bond Cleavage

Abstract

A mild domino rearrangement strategy for the direct access to substituted quinoline‐4‐carboxamides has been developed. This copper‐catalyzed coupling reaction of O‐acyl oximes with isatins in the presence of molecular oxygen as the sole oxidizing agent proceeds through a ring expansion of the isatins through cleavage of the two C–N bonds.

Synthesis of two quinolines from one substrate: The beginning of regulating the duality of free radicals

“…Formamid is hygroscopic, flammable and can strongly corrode copper, brass, lead and rubber 31 . Coupling of O-Acyl Oximes with Isatins to generate quinoline-4-carboxamides needs high temperature and the use of toxic solvent toluene 32 . Therefore, it is essential to explore facile, effective, and green synthetic methods for these unique compounds that have several potential applications in diverse fields of interest.…”

Divergent Synthesis of Quinolines: Exploiting the Duality of Free Radicals

“…To date, the synthetic methods of polysubstituted quinolines mainly include the [4 + 2] cycloaddition of aromatic imines and acrylates, cyclization of arylmethyl ketones and isatins, or substitution reactions on existing quinoline scaffold. 8 Despite the advancements in these methodologies, certain limitations persist, such as the need for expensive and hazardous materials, long reaction times, nongreen solvents, multistep processes, and high temperatures. Moreover, considering the broad biological activities of substituted quinolines, divergent synthesis is beneficial for their biological activities study.…”

Catalytic Heteroannulation for the Synthesis of Quinoline‐4‐Carboxamides Bearing Axial Chirality

“…[17] Almost at the same time, the group of Wu and Bathula independently reported the usage of ketoxime acetates to couple with isatins for the introduction of primary amides to the quinoline ring by using different catalytic systems. [18] It is worth noting that the above-mentioned catalytic cyclization processes based on isatin can not produce N,N-disubstituted tertiary quinoline-4-carboxamides, which might lead to the loss of opportunity for identifying and investigating the phenomenon of atropisomerism in these heteroaromatic amides-type chiral scaffolds.…”

“…The higher yield (83%) and shorter reaction time were obtained when n-hexane was used (Table 1, entry 15). Finally, the catalyst loading, substrate ratio as well as the effects of temperature and additive on the reaction were explored (Table 1, entries [16][17][18][19][20]. When 20 mol% of Fe(OTf) 3 or 2.0 equiv.…”