Ru‐Catalyzed Sequential Dehydrogenative Friedlander Reaction/sp³ C–H Activation/Knovenagel Condensation in the Regioselective Synthesis of Chimanine B Analogues

Abstract

Choline chloride (ChCl) based deep eutectic solvent (DES), facilitated the regioselective synthesis of (E)-1-(4-phenyl-2-styrylquinolin-3-yl)ethan-1-one (4), and (E)-3-phenyl-1-(4phenyl-2-((E)-styryl)quinolin-3-yl)prop-2-en-1-ones, (5) from the corresponding 2-amino-5-chloro benzhydrol, (1) in one-pot strategy. The 2-methyl-3-acetylquinoline generated in situ from the 2-amino-5-chloro benzhydrol, (1) and acetyl acetone, (2) via dehydrogenative Friedlander reaction in DES could enable subsequent regio-selective C-2 methyl group sp 3 C-H activation and rapid alkenylation with alcohols, (3) to provide the desired (E)-2-styrylquinolin-3-yl)ethan-1-ones, 4 in short reaction time [a] S.Figure 2. Choline chloride based DESs used in this work.quinolines employing different catalysts like Bronsted acids, [24] transition metals. [25] Friedlander reaction via an oxidative cyclization of 2-aminobenzyl alcohol with either ketones or alcohols were reported by Milstein, [26] Shim, [27] Yus, [28] Verpoort, [29] Kaneda, [30] employing Ru, Ir [31] and Pd [32] catalysis. Ahmed Kamal [33] and co-workers reported 5-nitrofuran-triazole derivatives by multicomponent reactions using CuSO 4 ·5H 2 O/sodium ascorbate/tBuOH/H 2 O. Recently, Xinhua Xu [34] and co-workers reported 3,4-dihydropyrimidin2-(1H)-ones/thiones using an air-stable zirconium(IV)-salophen perfluorooctanesulfonate complex as catalyst. Herein, we reported dehydrogenative cyclization of 2-amino-5-chloro benzhydrol with benzyl alcohol in presence of RuCl 2 (p-Cym) 2 using K 2 CO 3 :Glycol(1:1) and Ch-Cl:Oxalic acid(1:1) DESs. Ru catalyst was employed based on the oxidation studies of both primary and secondary alcohols. [26,27,35] The catalytic pathway of Ru catalysis and its role in the present reaction was evidneced from comparative reaction with and absence of the Ru catalyst, which indicated the necessitiy of RuCl 2 (pCym) 2. In the present study, other catalysts trials were ineffective. Further, optimised mol-% of RuCl 2 (p-Cym) 2 , with 5 mol-% a 60 % yield was observed while 15 mol-% provided 90 % yield (see supporting information). This strategy allowed the primary as well as secondary alcohols oxidization in K 2 CO 3 :Glycerol(1:1) [36] at pH 11 then tuned to acidic pH 1 by addition of Ch-Cl:Oxalic acid(1:1) DES for the in situ generation of quinoline. Likewise, the Ch-Cl:Oxalic acid (1:1) allowed the sp 3 C-H functionalization. Further tuning to the pH 12, with the addition of KOH facilitates the Knovenagel condensation. Results and DiscussionA convenient regioselective one-pot synthesis of Chimanine B analogues, for instances, the (E)-1-(4-phenyl-2-styrylquinolin-3yl)ethan-1-ones (4), and (E)-3-phenyl-1-(4-phenyl-2-((E)-styryl)quinolin-3-yl)prop-2-en-1-ones, (5) are presently reported from the corresponding 2-amino-5-chloro benzhydrol, (1), aromatic alcohols (3) as precursors. Interestingly, the 2-methylquinolone formed in situ in DES underwent regioselective methyl Csp 3 -H activation in one-pot to provide the alkenylated product, 4 in high yields and purity...

Copper-catalyzed dehydrogenative cyclization/alkenylation towards dihydroquinolinones

“…28,29 In this regard, our group has recently developed an efficient and environmentally sustainable method to synthesize N-heterocyclic compounds. [30][31][32] In a continuation of this, herein we have designed a sequential one-pot synthesis of alkenylated quinolinyl dihydroquinolinones, utilizing ketones 1, 1,3-cyclohexanediones 2 and alcohols 3, via C(sp 3 )-H functionalization/α-alkenylation, as shown in Scheme 1c.…”

Mn-Catalyzed Ligand-Free One-Pot Synthesis of (E)-6,7-Dihydrodibenzo[b,j][1,7]phenanthrolines and (E)-1,2,3,4-Tetrahydrobenzo[b][1,6]naphthyridines through Dehydrogenative Friedlander Annulation/C(sp3)–H Functionalization

“…38−42 DES has several advantages, including nontoxicity, biodegradability, low cost, easy synthesis, and good thermal stability; it acts as a catalyst as well as a solvent. 43,44 This article is licensed under CC-BY-NC-ND Our research team has recently focused on deep eutectic solvents, for example, Ir-, 45 Cu-, 46 and Ru-catalyzed 47 synthesis of quinolones, dehydrogenative Friedlander annulation, and C(sp 3 )−H functionalizations. In our continued research, Mncatalyzed dehydrogenative Friedlander annulation/alkenylation or C(sp 3 )−H functionalization is reported here in this article.…”

“…Our research team has recently focused on deep eutectic solvents, for example, Ir-, 45 Cu-, 46 and Ru-catalyzed 47 synthesis of quinolones, dehydrogenative Friedlander annulation, and C(sp 3 )–H functionalizations. In our continued research, Mn-catalyzed dehydrogenative Friedlander annulation/alkenylation or C(sp 3 )–H functionalization is reported here in this article.…”