Application of the Intramolecular Didehydro-Diels-Alder (IMDDA) Reaction for the Synthesis of Thieno[2,3- f ]isoindole-4(8)-carboxylic Acids

The reaction of 3-(thienyl)propargylamines with maleic anhydride, followed by a domino sequence involving successive acylation/[4+2] cycloaddition steps, leads to the formation of the thieno[2,3- f ]isoindole core. The key step, the intramolecular didehydro-Diels-Alder (IMDDA) reaction, proceeds with a high level of selectivity, yielding the target products - 7-oxo-5,6,7,8-tetrahydro-4 H -thieno[2,3- f ]isoindole-4(8)-carboxylic acids - in good yields. X-ray analysis and DFT calculations have revealed that the key step, the IMDDA reaction, proceeds via an exo transition allene state, resulting in the exclusive formation of a single isomer of the target heterocycle. © 2025. Thieme. All rights reserved.