Synthesis of 8-heteroaryl nitroxoline analogues via one-pot sequential Pd-catalyzed coupling reactions

Abstract

A series of 8-heteroaryl substituted quinolines were prepared, either by direct C-H arylation of five-membered heteroarenes, or Pd-catalyzed coupling of organoboron reagents with bromoquinolines. The use of (benzo)thiophenyl or (benzo)furanyl boron coupling partners allowed further C-H functionalization on the five-membered heteroaryl ring with aryl bromides in one flask to access a variety of polyconjugated molecular architectures. The developed methodology represents a simple approach towards 8-arylated analogues of the biologically interesting nitroxoline core.

The Influence of the Quinoline Moiety on Direct Pd‐Catalyzed Arylation of Five‐Membered Heterocycles

“…Recently we reported a focused set of compounds used to further explore the chemical space and the structure‐activity relationship of nitroxoline‐based derivatives . Consequently, we have also developed a one‐pot sequential Pd‐catalyzed coupling reaction for the direct arylation of 8‐heteroarylquinolines with aryl bromides giving rise to a variety of polyconjugated quinoline compounds . Accordingy, arylation of C2‐quinolyl‐substituted pyrroles led to formation of C3‐arylated products suggesting a directing ability of the quinoline nitrogen atom in the C–H activation reaction.…”

Quinazoline‐Directed C–H Bond Functionalization Catalyzed by Ruthenium(II) Carboxylate – Construction of Polyconjugated Aryl‐Heteroaryl Systems

“…Yang et al developed a Pd‐catalyzed intramolecular oxidative C–H amination of 2‐aryl‐substituted 3‐(arylamino)quinazolinones to access indazo[3,3‐ b ]quinazolinones . These results in addition to our own work regarding the successful ortho ‐arylation of phenylpyrimidines[11b] in the presence of a ruthenium(II) carboxylate catalytic system prompted us to explore the direct arylation of quinazoline derivatives by C–H bond cleavage of the C‐2–(hetero)aryl substituent.…”

“…Yet, there is still a great demand for the generation of new quinazoline libraries. As part of our ongoing interest in metal‐catalyzed functionalizations of (hetero)arenes by C–H activation, we reasoned that a quinazoline nucleus could undergo direct cleavage and further functionalization at the ortho ‐C–H bonds of a 2‐aryl substituent and, thus, enable the construction of highly conjugated quinazoline derivatives. Only limited examples, however, of the quinazoline ring acting as a directing group in a C–H functionalization have been demonstrated.…”

Cp*Rh(III)‐Catalyzed Directed C−H Methylation and Arylation of Quinoline N‐Oxides at the C‐8 Position

“…[38] In addition, Larionov developed the palladium-catalyzed C8 arylation and selective homocoupling of quinoline N-oxides. [45][46][47][48][49] Inspired by the previous work by Li [50] and our groups, [51] we disclose a Rh(III)-catalyzed C8 functionalization of quinoline N-oxides with organoboron reagents (Scheme 2). [40][41][42][43][44] However, related alkylation at the C8 position of quinoline N-oxides with organo-boron reagents remains unexplored.…”

“…[40][41][42][43][44] However, related alkylation at the C8 position of quinoline N-oxides with organo -1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 boron reagents remains unexplored. [45][46][47][48][49] Inspired by the previous work by Li [50] and our groups, [51] we disclose a Rh(III)-catalyzed C8 functionalization of quinoline N-oxides with organoboron reagents (Scheme 2).…”