Tethering Three Radical Cascades for Controlled Termination of Radical Alkyne peri-Annulations: Making Phenalenyl Ketones without Oxidants

• Published in: Journal of the American Chemical Society 2024-02, Vol.146 (6), p.4187-4211
• Main Authors: Hu, Chaowei, Kuhn, Leah, Makurvet, Favour D., Knorr, Erica S., Lin, Xinsong, Kawade, Rahul K., Mentink-Vigier, Frederic, Hanson, Kenneth, Alabugin, Igor V.
• Format: Article
• Language: English
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.3c13371

Although Bu3Sn-mediated radical alkyne peri-annulations allow access to phenalenyl ring systems, the oxidative termination of these cascades provides only a limited selection of the possible isomeric phenalenone products with product selectivity controlled by the intrinsic properties of the new cyclic systems. In this work, we report an oxidant-free termination strategy that can overcome this limitation and enable selective access to the full set of isomerically functionalized phenalenones. The key to preferential termination is the preinstallation of a “weak link” that undergoes C–O fragmentation in the final cascade step. Breaking a C–O bond is assisted by entropy, gain of conjugation in the product, and release of stabilized radical fragments. This strategy is expanded to radical exo-dig cyclization cascades of oligoalkynes, which provide access to isomeric π-extended phenalenones. Conveniently, these cascades introduce functionalities (i.e., Bu3Sn and iodide moieties) amenable to further cross-coupling reactions. Consequently, a variety of polyaromatic diones, which could serve as phenalenyl-based open-shell precursors, can be synthesized.