Room-Temperature and Transition-Metal-Free Intramolecular α-Arylation of Ketones: A Mild Access to Tetracyclic Indoles and 7-Azaindoles

Abstract

A novel approach for the synthesis of tetracyclic indoles and 7-azaindoles is reported. The strategy involves four steps, with a fast rt intramolecular α-arylation of ketones as key step. The reaction was inspected synthetically to achieve the synthesis of 11 novel tetracyclic structures with moderate to very good yields (39− 85%). Theoretical combined with experimental studies led us to propose a probable polar mechanism (concerted S N Ar).

Concerted Nucleophilic Aromatic Substitution Reactions

“…Carbon nucleophiles were used by MØdebielle, Rossi et al in the synthesis of tetracyclic indoles,f or example, 227 (Scheme 33 A) and azaindoles. [73] Computational studies were used to probe the mechanism of the reaction. Electron transfer was considered, but gave very high energy barriers.…”

Konzertierte nukleophile aromatische Substitutionen

“…227 (Schema A), und Azaindolen eingesetzt. Quantenchemische Studien wurden unternommen, um den Reaktionsmechanismus zu untersuchen . Ein Elektronentransfermechanismus wurde in Betracht gezogen, zeigte jedoch sehr hohe Energiebarrieren.…”

Direct photo-induced reductive Heck cyclization of indoles for the efficient preparation of polycyclic indolinyl compounds

“… 1 Due to the high negative reduction potential and bond energy of C(sp 2 )–Cl bonds [ e.g. , for PhCl, E red (PhCl/PhCl˙ − ) = −2.78 V vs. SCE; 2 BDE (C–Cl) = 97.1 kcal mol −1 ], 3 the reduction of aryl chloride to give an aryl radical usually requires harsh conditions, such as a strong base under thermal conditions 4 or ultraviolet (UV) light irradiation 5 is usually used. Highly reactive organic super-electron donors, 6 consecutive visible light-induced electron transfer reactions 7 and electrophotocatalysis 8 are also employed to activate aryl chlorides, via one-electron reduction.…”