Serendipitous Synthesis of Pyridoquinazolinones via an Oxidative C–C Bond Cleavage

Abstract

A direct one-pot copper-catalyzed oxidative C–C bond cleavage route to the synthesis of pyridoquinazolinones is described. This one-pot strategy involves a copper-catalyzed C–N coupling followed by concomitant C­(sp3)–H oxidation and amidation via oxidative C–C bond cleavage under an O2 atmosphere to deliver the target molecules in high yields.

Copper‐mediated annulation of 2‐aminoacetophenones and 2‐bromopyridines

“…Based on the results of previous studies, [10,12] a plausible mechanism was proposed as shown in scheme 2. An Ullmann-Goldberg typed C-N coupling would firstly afford the N-pyridyl substituted 2'-aminoacetophenone 4, which was oxidized to furnish the glyoxalic-typed intermediate 5.…”

“…The obtained species would undergo a sequence of cyclization/decarboxylation to yield the targeted pyrido-fused quinazolinone 3aa. [12] An alternative pathway would comprise the Cu/TEMPO comediated, partial oxidation of 4 to afford the phenylgloxal-typed intermediate 6. Nucleophilic addition followed by oxidation would furnish the N-…”

“…Recently, Kaliappan and coworkers developed a two-step coupling of 2'haloacetophenones and 2-aminopyridine, in the presence of CuI catalyst. [12] Herein we would like to report a general method for copper-catalyzed annulation of 2'-aminoacetophenones and 2-bromopyridines.…”

Synthesis of Fused Imidazoles and Pyrimidinones from 2‐Aminoazines

“…), Cu(acac) 2 (1 mol%) and Pybox (1.2 mol%) in MeOH at room temperature for 6 h. When compared with the A 3 -coupling reaction, the formation of intermediate 64 via propargylation of 2-aminopyridines at the pyridine-nitrogen with compound 62 was proposed as the initial step in a cascade reaction. Kaliappan et al [52] reported a direct synthesis of pyridoquinazolinone (66) from 2-aminopyridine (1 a, 1.2 equiv.) and 2-iodoacetophenone (65, 1.0 equiv.)…”

Application of 2-Aminopyridines in the Synthesis of Five- and Six-Membered Azaheterocycles

“…其中, 基于邻卤 苯乙酮的合成最常见 [99] . 例如, Kaliappan 课题组 [100] 最 近报道, 邻溴苯乙酮与 2-氨基吡啶 1 反应, 经 Ullmann-Goldberg 型偶联反应、铜(I)催化氧化加成、还原消除、 分子内成环、甲基被氧化为 CO 2 离去的历程, 生成吡啶 喹唑啉酮(Eq. 16).…”