Copper-catalyzed synthesis of aminoquinolines from β-(2-aminophenyl)-α,β-ynones using DMF as dual synthon

Abstract

The utilization of DMF as a dual synthon to serve as a methine source to introduce C2 carbon and nitrogen source to incorporate amino functionality in the 4th position of quinoline under Cu-catalysis.

Copper-Catalyzed Oxidative Cyclization of 2-Aminobenzamide Derivatives: Efficient Syntheses of Quinazolinones and Indazolones

“…Based on these findings and previous reports, 32,34,35 a plausible mechanism is proposed as presented in Scheme 5. DMF is first converted into the iminium ion A in the presence of O 2 and Cu(I), 32 and a nucleophilic addition reaction of iminium ion A with 1a generates B followed by elimination of dimethylamine.…”

“…Based on these findings and previous reports, 32,34,35 a plausible mechanism is proposed as presented in Scheme 5. DMF is first converted into the iminium ion A in the presence of O 2 and Cu(I), 32 and a nucleophilic addition reaction of iminium ion A with 1a generates B followed by elimination of dimethylamine. Subsequent aza-endo-trig cyclization results in the formation of D, which is then oxidized to yield the quinazolinone 2a product under the Cu(I)/O 2 condition (Scheme 5 i).…”

“…2,30 These results show the importance of DMF in the organic synthesis as an effective polar solvent and as a versatile reagent. Recently, we reported the synthesis of 3formylindoles and 3-acyl-4-aminoquinolines by coppercatalyzed oxidative annulation using DMF as a formyl 31 and dual synthon 32 to afford methine and N′,N-dimethyl functionality, respectively (Scheme 1a, b). These results inspired us to envision a copper-catalyzed synthesis of bicyclic Nheterocycles using readily available DMF.…”

A Journey from June 2018 to October 2021 with N,N-Dimethylformamide and N,N-Dimethylacetamide as Reactants

“…While Marinelli's team isolated (1H-indol-2-yl)(phenyl)methanone in 60% yield from microwave heating (140 • C) in DMF of o-phenylethynyl aniline in the presence of 0.2 equiv. of CuCl (Scheme 50a) [155], Lin and co-workers subsequently obtained (4-(dimethylamino) quinolin-3-yl)(phenyl)methanone in 71% yield from the reaction at 120 • C of the same substrate, in the same solvent with the same amount of CuCl, but under oxygen atmosphere, the yield increased to 82% with DMSO as the additive (Scheme 50b) [156]. As Marinelli's report was not cited by Lin's team, no explanation of the reactivity difference was provided.…”

“…According to DFT calculations reported in the first paper, activation of the triple bond by coordination to a Cu I (DMF) complex promotes intermolecular hydroamination, with preservation of the oxidation state of the catalyst [155]. Lin and co-workers assumed that oxygen oxidizes Cu I into Cu II [156], a reaction probably promoted by DMSO [157,158]. This redox system is associated with the thermal decomposition of DMF, a decisive step of the proposed mechanism, which agrees with labeling experiments using DCON(CD 3 ) 2 and H 13 CON(CH 3 ) 2 .…”