Total synthesis of (-)-cylindrocyclophane A facilitated by C-H functionalization

• 成果类型: Article
• 署名作者: Bosse, Aaron T.; Hunt, Liam R.; Suarez, Camila A.; Casselman, Tyler D.; Goldstein, Elizabeth L.; Wright, Austin C.; Park, Hojoon; Virgil, Scott C.; Yu, Jin-Quan; Stoltz, Brian M.; Davies, Huw M. L.
• 署名单位: Emory University; California Institute of Technology; Scripps Research Institute
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-10944
• DOI: 10.1126/science.adp2425
• 发表日期: 2024-11-08
• 页码: 641-646
• 关键词: enantioselective total-synthesis; transition-metal catalysis; cylindrocyclophanes

摘要

(-)-Cylindrocyclophane A is a 22-membered C2-symmetric [7.7]paracyclophane that bears bis-resorcinol functionality and six stereocenters. We report a synthetic strategy for (-)-cylindrocyclophane A that uses 10 C-H functionalization reactions, resulting in a streamlined route with high enantioselectivity and efficiency (17 steps). The use of chiral dirhodium tetracarboxylate catalysis enabled the C-H functionalization of primary and secondary positions, which was complemented by palladium-catalyzed C(sp2)-C(sp2) cross-couplings, resulting in the rapid formation of the macrocyclic core and all stereocenters with high regio-, diastereo-, and enantioselectivity. The use of a late-stage palladium-catalyzed fourfold C(sp2)-H acetoxylation installed the bis-resorcinol moieties. This research exemplifies how multilaboratory collaborations can produce substantial modernizations of complex total synthesis endeavors.