Microwave-assisted synthesis of 4,6-disubstituted isoindoline-1,3-diones by Diels-Alder reactions

The synthesis of 4,6-disubstituted isoindoline-1,3-diones through microwave-assisted Diels-Alder (DA) re-actions is reported. Chromones bearing an alpha,beta-unsaturated carbonyl system at C-3 were used as dienes and a scope of maleimides as dienophiles was investigated. The proposed mechanism involves a DA re-action of 3-benzoylvinylchromones with different maleimides, followed by chromanone ring opening and in situ oxidation. The observed aromatization of DA adducts was accomplished without employment of any oxidizing agent and can be explained by the presence of several acidic protons due to the electron -withdrawing groups (carbonyl groups), affording the 4,6-disubstituted isoindoline-1,3-diones in 15-59% yield. Among tested maleimides, N-phenylmaleimide revealed to be the most reactive dienophile, yield-ing the corresponding 2-phenylisoindoline-1,3-dione in 59% yield. (c) 2022 The Authors. Published by Elsevier B.V.

Automated summary

The synthesis of 4,6-disubstituted isoindoline-1,3-diones through microwave-assisted Diels-Alder reactions is reported. A range of chromones and maleimides were utilized to investigate the reaction scope. The proposed mechanism involves a Diels-Alder reaction, ring opening, and in situ oxidation. The yields of 4,6-disubstituted isoindoline-1,3-diones ranged from 15% to 59%, with N-phenylmaleimide showing the highest reactivity in producing the desired product.