Regioselective Synthesis of Annulated Quinoline and Pyridine Derivatives by Silver-Catalyzed 6-endo-dig Cycloisomerization

Abstract

3H-pyrano[3,2-f]quinoline-3-one, 4-methyl-4,7-phenanthrolin-3(4H)-one, and 1,3-dimethylpyrido[3,2-d]pyrimidine-2,4(1H,3H)-dione derivatives have been synthesized by hitherto unreported silver-catalyzed 6-endo-dig mode of cycloisomerization from various N-propargylated heterocyclic compounds. The silvercatalyzed reaction provides the synthesis of potential bioactive compounds in excellent yields.There is flurry of activities on the synthesis of quinoline and its annulated derivatives due to their broad spectrum of biological profiles, which includes antialergic, antidiabetic, antimicrobial, analgesic, insecticidal, antifungal, antipyretic, tyrosine kinase inhibition, and also cytotoxic properties. 1 Due to these bioactivities quinoline derivatives are widely used in pharmaceutical and agrochemical sectors, besides these derivatives are also used as functional materials. 2 The quinoline derivatives have gained considerable attention due to their central role as building blocks in the synthesis of natural products. 3 On the other hand natural products possessing coumarin, quinolone, and uracil subunits show wide range of bioactivity. 4 There are many alkaloids which contain pyrido-coumarin, pyrido-quinolone skeleton, due to the presence of these cores the alkaloids are also bioactive. 5 Some examples of natural products are dutadrupine, helietidine, geibalansine, and amphimedine. 6 Moreover bioactivity of pyrido-pyrimidines are well known, 7 besides their antibacterial and antiallergic properties they also inhibit enzyme adenosine kinase (AK) and dihydrofolate reductase (DHFR). 8 Recently, it has been found that substituted pyridines efficiently inhibit HMG-CoA reductase and cholesterol transport proteins. 9Traditional approaches 10 have frequently been employed for the synthesis of quinoline ring system in the total synthesis of quinoline based alkaloids. However, all these reactions usually require harsh conditions, tedious reaction procedure, or give poor yield. Over the last two decades, there has been growing interest for the development of syntheses of quinoline derivatives, which include radical reaction, 11 iodine-mediated cyclization, 12 and metal-catalyzed reaction. 13 Nevertheless, these are improvements over traditional methods. However, these methods also have some limitations. Some methods are not environmentally benign in terms of toxicity, 11,12 some are time consuming processes or having different byproducts. 13 A thorough search of literature reveals that there are a few examples of activated gold-and copper-catalyzed cycloisomerization reactions to afford substituted pyridine and quinoline derivatives. 14 To our knowledge, there is no such report for the synthesis of bioactive pyridocoumarin or pyridoquinolone or pyridopyrimidine solely by silvercatalyzed reaction. This prompted us to undertake a study to develop a methodology for the synthesis of these heterocycles. We report here the results of our investigation.The required precursors 3a-f were prepared in high yields by the reaction of 1a-c w...

Synthesis Through Three‐Component Reactions Catalyzed by FeCl3 of Fused Pyridocoumarins as Inhibitors of Lipid Peroxidation

“…Silver‐catalyzed cycloisomerization of propargylaminocoumarins resulted also in pyridocoumarins. The formation of the pyranone moiety is realized from quinolinols by Pechmann condensation or reactions with dimethyl acetylene dicarboxylate (DMAD) and PPh 3 , from quinolinequinones via Wittig reactions or condensation with diethyl aminofumarate, by the oxidation of a pyran ring, formed in situ by electrocyclization of cis ‐dienals, and demethylation and condensation of o ‐substituted (2′‐methoxyphenyl)pyridine carboxylic acids. …”

“…The synthesis of pyridocoumarins has been achieved either by formation of the pyridine or the pyranone moieties. Construction of the pyridine moiety involves the iodocyclization of 6‐(but‐2‐ynyl)aminocoumarin in the presence of I 2 , developed by Majumdar et al .…”

An Overview of Ag‐catalyzed Synthesis of Six‐membered Heterocycles

“…Majumdar and co‐workers were successful in establishing a synthetic procedure for the formation of 1,3‐dimethylpyrido[3,2‐ d ]pyrimidine‐2,4(1 H ,3 H )‐dione, 4‐methyl‐4,7‐phenanthrolin‐3(4 H )‐ one and 3 H ‐pyrano[3,2‐ f ]quinoline‐3‐one 10 scaffolds [19] . 6‐ endo‐dig cycloisomerization of diverse N ‐propargylated heterocyclic motifs 9 were catalyzed by 10 mol % AgSbF 6 in DMSO (Scheme 5).…”

Green Synthesis of Benzo or Cyclopenta[j][1,7]phenanthroline Derivatives in EtOH under Catalyst‐free Conditions

“…Therefore, a number of procedures have been reported to prepare these potential active heterocycles in recent years . Of which, quinolin‐6‐amine is an important reactant to the synthesis of [4,7]phenanthroline derivatives , such as benzo[ b ][4,7]phenanthroline, cyclopenta[ b ][4,7]phenanthroline, and indeno[2,1‐ b ][4,7]phenanthroline.…”