Silver-Catalyzed Tandem Synthesis of Naphthyridines and Thienopyridines via Three-Component Reaction

Abstract

An efficient approach for the silver-catalyzed regioselective tandem synthesis of highly functionalized 1,2-dihydrobenzo[1,6]naphthyridines 6a-z and 7a-e by the reaction of ortho-alkynylaldehydes 3a-n with amines 4a-d and ketones 5a-c/active methylene compounds 5d-g, under mild reaction conditions, is described. The scope of the developed chemistry was successfully extended for the direct synthesis of 1,2-dihydrobenzo[4,5]thieno[2,3-c]pyridines 8a-e, which is known as the sulfur analogue of β-carbolines. Naphthyridines 6a-z and thienopyridines 8a-e were obtained via dual activation concept using l-proline as organocatalyst; however, naphthyridines 7a-e were synthesized without using organocatalyst. The reaction shows selective N-C bond formation on the more electrophilic alkynyl carbon, resulting in the regioselective 6-endo-dig-cyclized products. Reactivity behavior of electron-deficient and electron-rich ortho-alkynylaldehydes in the synthesis of naphthyridines and thienopyridine by three-component reaction is supported by the control experiment.

Silver and gold-catalyzed multicomponent reactions

“…Moreover, an extension to γ-ketoalkyne encompassed in diverse heterocyclic frameworks (quinoline, pyridine or benzo[ b ]thiophene) has been reported [59]. …”

Alkynes in Organocatalysis

“…A multicomponent reaction of 2-alkynylbenzaldehydes 58 a, anilines 59 a and ketones 60 a was reported to afford 1,2-dihydroisoquinoline derivatives 61 a, as outlined in Scheme 30. [55] l-Proline promotes the attack of ketone 60 a to the aldimine, which is generated in situ between the aldehyde 58 a and the aniline 59 a (enamine catalysis). On the other hand, the silver catalyst activates the triple bond towards the intramolecular nucleophilic attack that affords the cyclization (Lewis acid catalysis).…”

Novel Sono-synthesized Triazole Derivatives Conjugated with Selenium Nanoparticles for cancer treatment

“…In order to complete these needs, chemical reactions are proceeds in solvent-free, water as a solvent, ionic liquids, bio-based chemicals and supercritical fluids as green solvents. The increasing interest to employ fruit juice in biocatalysts and in the synthesis of heterocyclic was achieved [31][32][33][34][35][36][37][38]. Recently, more attention has been attracted on targeting anticancer drugs disrupting tumor-specific cell signaling, cell division, energy metabolism, gene expression, drug resistance and so on.…”