Copper‐Catalyzed Aerobic Oxidative Cyclization of Anilines, Aryl Methyl Ketones and DMSO: Efficient Assembly of 2‐Arylquinolines

Abstract

A Cu‐catalyzed C−H cyclization of simple anilines with ketones and DMSO as a one‐carbon source has been developed. Using an aerobic oxidative protocol, a number of ketones and anilines could be easily converted to 2‐arylquinolines, rather than 4‐arylquinolines, thus providing a highly atom‐economical and simple approach to biologically significant 2‐arylquinolines. Based on the preliminary experiments, a plausible mechanism is proposed.magnified image

Iron Single Atom Catalyzed Quinoline Synthesis

“…[13,14] As shown in Figure 4A, a three-component, oxidative cyclization reaction employing feedstock chemicals aniline, acetophenone and dimethyl sulfoxide (DMSO) as the starting materials was pursued. [15] The formation of the desired product (6-methoxy-2-phenylquinoline) together with possible side products (imine and amide from aldol condensation as well as azo-compound and phenazine from the homo-coupling of arylamine) were monitored by gas chromatography-mass spectrometry (GC-MS) in Figure 4A. As illustrated in Figure 4B and Figure S22, Supporting Information, our SACs gave the highest GC selectivity toward quinoline derivatives among all catalysts examined (≈68%, 44%, 42%, and 54% for Fe, Co, Ni, and Cu-800 SAC with 10 mol% catalyst loading).…”

“…[13,14] Owing to the requirement for specialized substrates (ortho-substituted aniline) and the lack of multifunctional capability, researchers have devised the three-component annulation reaction of readily available materials, including transition metal-catalyzed Povarov reaction using arylamine, aldehyde, and a third component (alkene, alkyne, etc.). [15,16] The conundrum is that homogeneous reactions usually entail tedious separation of catalyst residues, whereas the use of heterogeneous catalysts leads to undesired side reactions. [17,18] There is therefore a compelling need to develop SACs that enable efficient access to valuable quinoline derivatives with high selectivity and are easily separable from the reaction mixtures.…”

Metal‐Free Synthesis of 2‐Aryl Quinazolines via Tandem C−H/N−H Bond Functionalization

“…Firstly, DMSO decomposes upon heating to produce acidic methanethiol, after which the reaction mixture becomes weakly acidic [27a] . Meanwhile, DMSO dehydrates to form intermediate 1 with an S=C bond [30a,b,f] . 1 a then undergoes a nucleophilic addition reaction with 1 to produce intermediate 2 , [30e] and simultaneously loses methyl mercaptan to obtain imine 3 [30f] as identified by high performance liquid chromatography‐mass spectrometry (LC‐MS) (see support information).…”

Recent synthetic efforts in the preparation of 2-(3,4)-alkenyl (aryl) quinoline molecules towards anti-kinetoplastid agents

“…122 It should be noted that early Patil and Raut developed a copper-catalysed tandem addition/cycloisomerisation reaction giving access to 2-arylquinolines using 2-aminobenzaldehydes and terminal alkynes as substrate 123 and a microwave-assisted solid acid-catalysed synthesis of 2-arylquinolines from anilines and cinnamaldehydes in the presence of montmorillonite K-10 was also reported by Török and coworkers. 124 Recently, Liang and co-workers reported a simple method for the synthesis of substituted quinoline derivatives by copper-catalysed annulation of anilines with terminal acetylene esters, e.g., 1-phenylprop-2-ynyl acetate 125 and Guo and colleagues 126 developed an aerobic oxidative protocol based on a Cu-catalysed C-H cyclization (10 mol% CuCl 2 $2H 2 O) of simple anilines with acetophenones and DMSO as a one-carbon source for preparing easily diverse 2-arylquinolines. Instead of 2-aminobenzyl alcohols, 2-nitrobenzyl alcohols can also be used in the 2-arylquinoline synthesis that is catalysed by Fe-catalyst and formic acid as a redox moderator to ll the electron gap of the global redox condensation process.…”