Cu(OTf)₂ Enhanced Intramolecular Nucleophilic N-Arylation of 2-Amino-3-arylquinolines

Abstract

In the presence of Cu­(OTf)2 (5 mol %) and KO t Bu, a synergistic effect of the N-arylation process on 2-amino-3-arylquinolines is observed. Within 4 h, this method provides a wide variety of norneocryptolepine analogues with good to excellent yields. Overall, a double heteroannulation strategy for the synthesis of indoloquinoline alkaloids from nonheterocyclic precursors is demonstrated. Mechanistic investigations establish that the reaction proceeds via the SNAr pathway. Despite moderate yields, the one-pot, two-step double heteroannulation illustrates that this procedure is highly atom-efficient. Neocryptolepine, a natural product, is also synthesized from indoloquinoline. A brief study of the photophysical properties of selected norneocryptolepine analogues is also discussed.

HFIP-mediated C-3-alkylation of indoles and synthesis of indolo[2,3-b]quinolines & related natural products

“…Among the various indole derivatives, C-3 alkylated indoles are of prime importance due to their enormous chemical diversity and broad spectrum activity profile and accordingly their syntheses have attracted considerable interest from the organic chemistry community. 4 Similarly, indolo[2,3- b ]quinolines represent another class of indole-derived heterocycles with well documented bioactivities like antimicrobial, anticancer, antiplatelet, DNA intercalating and topoisomerase II inhibitory activities. 5–7 This captivating bioactivity profile of both subclasses along with their broad distribution in natural and synthetic compounds has been a driving force for developing new synthetic strategies in this direction.…”