Unexpectedly Regioselective Diels‐Alder Reactions of New Unsymmetrical Benzoquinones: A Convenient Synthetic Entry to Uniquely Substituted Decalins

• Published in: Chemistry : a European journal Vol. 30; no. 55; pp. e202401068 - n/a
• Main Authors: Maier, Lukáš, Němečková, Dana, Akavaram, Naresh, Kalla, Erik, Semrád, Hugo, Matyasková, Olivie, Munzarová, Markéta, Daďová, Petra, Kubala, Lukáš, Švenda, Jakub, Paruch, Kamil
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.10.2024
• Subjects: Benzoquinone; Benzoquinones; Chemical synthesis; Decalins; Diels-Alder reaction; Diels-Alder reactions; Forskolin; Forskolin analogs; Regioselectivity; Substitutes; Forskolin analogs; Diels-Alder reaction; Regioselectivity; Benzoquinones; Decalins
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.202401068

We report flexible synthesis of new unsymmetrically 2,6‐disubstituted benzoquinones (33 examples) and a systematic study of their reactivity in the Diels‐Alder reaction. The Diels‐Alder reactions of selected unsymmetrical benzoquinones with seemingly similar substituents were found to proceed with high regioselectivity and the formation of selected experimentally observed main products was rationalized by theoretical (DFT) calculations. The findings can be exploited in the convenient preparation of densely substituted and stereochemically defined decalins with unique angular substituents at ring fusion. We also demonstrate the usefulness of this methodology in complex molecule synthesis through the total synthesis of a novel forskolin analog possessing an ethyl group at the fusion of the rings B and C. We report flexible synthesis of new unsymmetrically 2,6‐disubstituted benzoquinones (33 examples) and their Diels‐Alder reactions proceeding with high (and rather unpredictable) regioselectivity. These experimental findings were rationalized by DFT calculations and exploited in the convenient preparation of uniquely substituted and stereochemically defined decalins, and a novel forskolin analog with ethyl group at the fusion of the rings B and C.