Iridium Acylnitrenoid-Initiated Biomimetic Cascade Cyclizations: Stereodefined Access to Polycyclic δ‑Lactams

• Published in: Journal of the American Chemical Society 2023-11, Vol.145 (45), p.24724-24735
• Main Authors: Tufano, Eleonora, Lee, Euijae, Barilli, Matteo, Casali, Emanuele, Oštrek, Andraž, Jung, Hoimin, Morana, Marta, Kang, Jihye, Kim, Dongwook, Chang, Sukbok, Zanoni, Giuseppe
• Format: Article
• Language: English
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.3c08331

Ring-fused azacyclic compounds are important building units in the synthesis of biorelevant natural products, pharmaceutical agents, and molecular materials. Herein, we present a new approach to these condensed azacycles by a biomimetic cascade cyclization of arylalkenyl dioxazolones. This cascade reaction was found to proceed with excellent stereoselectivity and a high functional group tolerance. The substrate scope of arylalkenyl dioxazolones turned out to be highly flexible and extendable to additional terminating subunits, such as heteroaryl and alkynyl moieties. This biomimetic cyclization was elucidated to be initiated by an intramolecular transfer of the in situ generated electrophilic Ir-acylnitrenoid to the tethered olefinic double bond, leading to a key N-acylaziridine intermediate, which is in turn reacted with pendant (hetero)­arenes or alkynes in a highly regio- and stereoselective manner to produce ring-fused azacyclic compounds.