Application of the Intramolecular Diels–Alder Vinylarenе (IMDAV) Approach for the Synthesis of Thieno[2,3-f]isoindoles

• DOI: 10.1055/s-0039-1690833
• Publication Date: 2020-03-12T23:46:30Z
• Authors: Mykola D. Obushak; Fedor I. Zubkov; Maryana A. Nadirova; Yevhen-Oleh V. Laba; Vladimir P. Zaytsev; Julya S. Sokolova; Kuzma M. Pokazeev; Victoria A. Anokhina; Victor N. Khrustalev; Yuriy I. Horak; Roman Z. Lytvyn; Miłosz Siczek; Vasyl Kinzhybalo; Yan V. Zubavichus; Maxim L. Kuznetsov
• Keywords: Aromatization; Isoindole; Maleic anhydride; Maleimide; Allylamine

3-(Thien-2-yl)- and 3-(thien-3-yl)allylamines, readily accessible from the corresponding thienyl aldehydes, can interact with a broad range of anhydrides α,β-unsaturated acids chlorides (maleic, сitraconic­, phenyl maleic anhydrides, сrotonyl сinnamyl chlorides, etc.) leading to formation thieno[2,3-f]isoindole core. Usually, reaction sequence involves three successive steps: acylation nitrogen atom initial allylamine, intramolecular Diels–Alder vinylarenе (IMDAV) reaction, final aromatization dihydrothiophene ring in adducts. The scope limitations proposed method were thoroughly investigated. It was revealed aid X-ray analysis that key step, IMDAV proceeds through an exo-transition state, giving rise exclusive single diastereomer target heterocycle. In case allows obtain functionally substituted carboxylic acids, which are potentially useful substrates for further transformations subsequent bioscreening.