A Three‐component Cascade Cyclization to Construct 3‐(2‐Oxopropyl)‐2‐arylisoindolinone Derivatives via Copper‐catalyzed Annulation

Abstract

An efficient synthesis of a variety of poly‐substituted isoindolinone derivatives via copper‐catalyzed three‐component cascade cyclization among 2‐formylbenzonitriles, alkyl aryl ketones/prop‐1‐en‐2‐ylbenzene and diaryliodonium salts is achieved. Various isoindolinone derivatives could be obtained in good to excellent yields. A concise synthesis of dihydroisoindolo[2,1‐a]quinolin‐11(5H)‐ones have been achieved using this method.magnified image

Copper-Catalyzed Ring Expansion of Cyclopropyl Ketones/Formation of N-acyliminium/Hetero-[4 + 2]-Cycloaddition: A Route to Substituted Pentacyclic Isoindolin-1-one

“…The proposed mechanism involved an intermediate N -aryl nitrilium cation, which was a highly reactive species and can easily undergo a coupling reaction forming new C–C bonds simultaneously . Two other examples of our group demonstrate this reaction strategy, and 2,3-disubstituted isoindolin-1-ones were synthesized …”

Isoindolinone Synthesis via One‐Pot Type Transition Metal Catalyzed C−C Bond Forming Reactions

“…The multicomponent methodology was further expanded to encompass alkyl aryl ketones and α‐methylstyrene instead of arenes to generate isoindolinone derivatives and dihydroisoindolo[2,1‐ a ]quinolin‐11(5 H )‐ones in moderate to excellent yields (Scheme 97 C). [184c] Finally, the three‐component cascade cyclization methodology was applied to cyclopropyl ketones constructing fused polycyclic isoindolinones. Here the final step involves a hetero‐[4+2]‐cycloaddition reaction between an N ‐aryl nitrilium cation and dihydrofuran derivative formed from the cyclopropyl ketone (Scheme 97 D).…”

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

“…Starting from several aryl and aliphatic ketones 89 , more than thirty isoindolinones 90 were obtained, with three points of diversity around the lactam core. Overall, aryl ketones containing electron-donating and electron-withdrawing functions and even a heteroaryl group delivered better yields than dialkyl ones (Scheme 26, path A) [104]. When cyclopropyl ketones 91 were used as substrates, a ring expansion and a new quaternary centre formation happened through the multicomponent reaction to produce pentacyclic derivatives 92 (Scheme 26, path B) [105].…”