Synthesis of Electron‐Deficient Tetrahydro‐ and Dihydroimidazo[1,2‐f]phenanthridines by Microwave‐Mediated IMDAF Reactions

Abstract

N‐Substituted tetrahydroimidazo[1,2‐f]phenanthridines (TIPs) and dihydroimidazo[1,2‐f]phenanthridines (DIPs) have a variety of interesting properties, but structural variations of these compounds have, until now, included nitrogen substituents. Herein, TIPs and DIPs that have electron‐withdrawing groups on the phenanthridine moiety have been synthesized. A microwave‐mediated one‐pot intramolecular Diels–Alder reaction of furan (IMDAF) and subsequent aromatization were employed as the key steps. The electron‐deficient dihydrophenanthridines constructed by an IMDAF were oxidized in situ by 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ), and the salts generated were treated with benzylamine to give N‐benzyl TIP compounds. These TIPs were remarkably stable towards air‐mediated oxidation relative to those TIPs that do not contain electron‐withdrawing substituents and were isolated in high yields. Electron‐deficient TIPs were easily oxidized to give the corresponding DIPs by treatment with N‐bromosuccinimide.

Stereoselective Synthesis of Hexahydroimidazo[1,2-a]quinolines via SN2-Type Ring-Opening Hydroarylation–Hydroamination Cascade Cyclization of Activated Aziridines with N-Propargylanilines

“…On the other hand, only a few reports are known in the literature for the synthesis of dihydro-1H-imidazophenanthridinium compounds. 6,7,13 However, to date, there is no report available in the literature for the synthesis of 1,2,3,3a,4,5-hexahydroimidazo[1,2-a]quinolines. The activated aziridines and azetidines are attractive building blocks for the synthesis of high-value acyclic and cyclic nitrogenous compounds.…”

“…Structurally analogous phenanthridinium derivatives are also efficient DNA-intercalating agents with antitumor properties . Recently, dihydro-1 H -imidazophenanthridinum compounds (DIP, II and III ), − more planar imidazophenanthridinium moieties (IP, IV ), as well as less planar tetrahydroimidazophenanthridines (TIP, V and VI ) have been found to exhibit interesting biological activities (Figure ). Therefore, the development of efficient and novel synthetic routes to such compounds with greater selectivity and wide structural diversity is of significant research interest among organic and medicinal chemists.…”

“…Various synthetic routes to benzimidazo­[1,2- a ]­quinolines include sequential S N Ar and intramolecular Knoevenagel condensation of 2-methyl-1 H -benzimidazoles and 2-fluorobenzaldehydes, Pd-catalyzed intramolecular Buchwald–Hartwig aryl amination of 2-(2′-bromoanilino)­quinolines, photochemical dehydrocyclization reaction of benzimidazolyl-substituted acrylonitriles, Cu-catalyzed cascade reactions, Rh­(III)-catalyzed C–H activation cascade reactions of imidamides and anthranils, etc. On the other hand, only a few reports are known in the literature for the synthesis of dihydro-1 H -imidazophenanthridinium compounds. ,, However, to date, there is no report available in the literature for the synthesis of 1,2,3,3a,4,5-hexahydroimidazo­[1,2- a ]­quinolines.…”