Year: 2026
Type: article
Abstract: Embedding functional motifs into bridged scaffolds is a powerful strategy for molecular recognition and drug design, yet imide-bridged medium-ring systems have remained synthetically inaccessible. Here, we report an expedient de novo synthesis of imidebridged bicyclo[4.3.1]decane scaffolds, featuring a highly strained anti-Bredt olefin and a twisted seven-membered imide ring, with excellent diastereoselectivity (>20:1 dr). The one-pot, palladium-catalyzed sequential reaction of isocyanides with allenyl butenoates proceeds with complete atom economy and high bond-forming efficiency. Mechanistic studies reveal that efficient leaving-group recapture and a highly reactive inverse-electron-demand type II intramolecular Diels-Alder (IMDA) reaction are both critical to this transformation. Notably, these unprecedented products display promising antiproliferative activity against a panel of cancer cell lines, highlighting their potential for antitumor drug discovery.
DOI: 10.1002/anie.8236861
Authors: Yi Wang, Huanfeng Jiang, Wanqing Wu
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: bronze
OpenAlex ID: W7225468330