Transition‐Metal‐Free Synthesis of N‐Substituted Phenanthridinones and Spiro‐isoindolinones: C(sp²)−N and C(sp²)−O Coupling through Radical Pathway

Abstract

Iodine-mediated intramolecular coupling of CÀ H and NÀ H bonds through radical pathways has been achieved for the synthesis of substituted phenanthridinones from 2phenylbenzamides using iodine, succininmide and di-tertbutylperoxide (DTBP) oxidant in dichloroethane at 130°C. The developed protocol provides substituted phenanthridinones, particularly N-alkyl substituted, which are difficult to access either by base-mediated or transition-metal-catalyzed methodologies due to acidic nature of the CÀ H bond adjacent to nitrogen atom in the amides. Serendipitously, switching the oxidant from DTBP to phenyliodine(III) diacetate (PIDA) afforded spiro-isoindolinones, involving intramolecular CÀ N, intermolecular CÀ O coupling and dearomatization of the phenyl ring in one pot.

Palladium‐Catalyzed Annulation of Arylbenzamides with Diaryliodonium Salts

“…However, the substrates of such cylizations through sequential aryl‐aryl and N ‐aryl coupling is rather limited, which often focuses on N ‐methoxybenzamides. In addition, the synthesis of substituted phenanthridinones from 2‐phenylbenzamides was also achieved with iodine‐mediated intramolecular coupling reactions through radical pathways [3g] . However, few report was recorded with N ‐arylbenzamides as the substrate for direct cyclization to enrich the N ‐aryl phenanthridinone family.…”

Latest Advancements in Transition‐Metal‐Free Carbon‐Heteroatom Bond Formation Reactions via Cross‐ Dehydrogenative Coupling

“…[9] Verma et al reported an intramolecular CÀ H amination in 2phenyl benzamides for CÀ N bond formation in phenanthridinones (Scheme 3). [10] This metal-free oxidative cyclization occurred using DTBP, iodine, succinimide in DCE at 130 °C for 12 h to afford mainly N-alkylated phenanthridinones which otherwise were difficult to synthesize conventionally. A radical pathway has been proposed for the reaction.…”

Synthetic Strategies in the Preparation of Phenanthridinones

“…When the substrate was bearing OTBS-group, the intermediate 29-C delivered spirolactam 35. Later, Verma et al reported a cyclization of 2-phenylbenzamides for the preparation of phenanthridinones using iodine, succinimide, and di- tert -butylperoxide (DTBP) as oxidant [ 125 ]. It has been shown that 2′-iodo-[1,1′-biphenyl]-2-carboxamide could be cyclized into phenathridinone under Ni-catalysis in the presence of boronic acid [ 126 ].…”