Synthesis of N-substituted isoindolinones via a palladium catalysed three-component carbonylation – amination – Michael addition cascade

Abstract

We herein describe a novel palladium catalysed three-component cascade process involving carbonylation of an aryl iodide to generate an acyl palladium(II) species that is intercepted by a primary aliphatic or aromatic amine, amide, or sulfonamide followed by intramolecular Michael addition to furnish N-substituted isoindolinones in good yield. Overall, the cascade results in the formation of one C—C and two C—N bonds, one ring and one stereocentre.Key words: isoindolinone, palladium, cascade, amidation, sulfonamidation.

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

“…Indeed, a seminal contribution also made use of a similar Pd-catalysed carbonylation followed by amide formation and cyclization in a three-component reaction between aryl iodides, incorporating a Michael acceptor 105 , amines and amides 2 and carbon monoxide ( 23 ) (Scheme 30) [108].…”

Chiral Phase‐Transfer‐Catalyzed Intramolecular aza‐Michael Reactions for the Asymmetric Synthesis of Isoindolinones

“…As most isoindolinones have been synthesized directly from ortho ‐halogenated benzamides through fast palladium‐catalyzed tandem Heck and aza‐Michael reactions,6a–6j the stereoselectivity of the synthetic pathway is hard to control, and the isolation of key reaction intermediates is rather difficult 6h,6i…”

High-yielding synthesis of 1-isoindolinone derivatives via palladium-catalysed cycloaminocarbonylation

“…A synthetic method for obtaining bis(isoindolinones) starting from aryl chlorides in nickel(0)-catalysed reaction was described. 13 Palladium-catalysed reactions of 2-iodo-Nsubstituted benzamides, 14 that of aryl iodides in carbonylationeami nationeMichael addition cascade 15 and that of 2 0 -bromoacetophenone with primary amines under carbon monoxide 16 proved to be highly efficient for the synthesis of the 1-isoindolinone scaffold. Isoindolinones via room temperature palladium nanoparticle-catalysed carbonylationeamination cascade were synthesised.…”