A Pd-catalyzed direct entry to 11-substituted 6H-isoindolo[2,1-a]indol-6-one derivatives as potential anticancer agents

Abstract

11-Substituted 6H-isoindolo[2,1-a]indol-6-ones are preparedviaa sequential intramolecular Heck reaction of dihaloN-allyl substitutedN-arylbenzamide derivatives.

One-Step Synthesis of Isoindolo[2,1-a]indol-6-ones via Tandem Pd-Catalyzed Aminocarbonylation and C–H Activation

“…Apparently, moderate yields of the products are still higher than the overall yields of known multistep methods for the construction of the required isoindoloindole skeleton. 4,7,9 In all examined reactions (Scheme 3), various symmetrical bromoarenes were used, eliminating the problems with the regioselectivity of this tandem reaction. To extend the generality of this method, the reactions of unsymmetrically substituted aromatic derivatives were examined.…”

“…The chemistry and biological activity of isoindolo­[2,1- a ]­indol-6-ones 1 , many of which are important scaffolds of drugs and bioactive compounds, have drawn considerable interest in the field of organic chemistry over the last few years. Some of the isoindoloindolone derivatives have been shown to be potent melatonin MT 3 and serotonin 5-HT 6 ligands, topoisomerase-II inhibitors, anticancer agents, and potential antagonists of the human neurokinin-1 (hNK 1 ) receptor in the central nervous system . In addition, such a tetracyclic system containing an indole ring is also a valuable precursor in the organic synthesis (e.g., for the synthesis of the NorA efflux pump inhibitor).…”

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

“…In 2015, Pal and co-workersr eported ad ouble Heck reaction to yield indolone-fused isoindolinone rings starting from dihalo N-allyl substituted N-arylbenzamide derivatives. [99] This methodology is based on the reactivity differences of the aromatic halideso ft he startinga mides towardst he Pd-catalyst (Scheme 45 A). The authors proposed that substrates with more reactive halideso nt he aniline ring (X in Scheme45A) than on the aroyl moiety (Y in Scheme 45) is essential for this reaction.…”

“…In 2015, Pal and co‐workers reported a double Heck reaction to yield indolone‐fused isoindolinone rings starting from dihalo N ‐allyl substituted N ‐arylbenzamide derivatives [99] . This methodology is based on the reactivity differences of the aromatic halides of the starting amides towards the Pd‐catalyst (Scheme 45 A).…”

Dibenzo[b,e]azepin-6-ones and Seven-Membered Sultam Derivatives: Convenient Synthesis via Palladium-Catalyzed Regioselective Intra­molecular Heck Reaction and Application towards Drug-Like Small Molecules

“…3a-g were in turn synthesized in 53-78% yields by twostep reactions of 2-iodoaniline (1) with commercially available 2-bromobenzoyl chloride or 2-bromobenzenesulfonyl chloride followed by N-alkylation of the resulting monosubstituted amide 2a/sulfonamide 2b (Scheme 2). 29,31 For the construction of dibenzoazepinone core, we initiated our investigation with the bromo N-alkyl-substituted N-styrenyl benzamide 4a as a model precursor. Initially, when the substrate 4a was reacted under the literature reported Heck conditions, 5 phenanthridinone framework 6a was obtained as a major product (62%) instead of dibenzo [b,e]azepin-6-one derivative 5a (Scheme 3).…”