Divergent Asymmetric Synthesis of Bonnadiene and ent ‐Polytrichastrene B

作者：Hui Wang, Lihua Wei, Jiayu Huang, Linsheng Wang, Haobo Peng, Huanfeng Jiang, Jian Wu, Zhiqiang Ma · 发表于：Angewandte Chemie International Edition · 年份：2025 · DOI：10.1002/anie.202507961 · 被引用次数：7 · 研究领域：Cyclopropane Reaction Mechanisms、Phytochemistry and biological activities of Ficus species、Synthetic Organic Chemistry Methods

Abstract We report herein the first asymmetric total synthesis of bonnadiene and ent ‐polytrichastrene B, two diterpenoids that share a common spirotricyclic skeleton. Notably, ent ‐polytrichastrene B also features a highly strained, sterically congested tetrasubstituted cyclopropane moiety, presenting significant synthetic challenges in both its construction and stereochemical control. The synthesis features: (1) palladium‐catalyzed enantioselective redox‐relay Heck alkenylation between electron‐withdrawing alkenyl triflate and primary alkenol to form the stereocenter at C7; (2) diastereoselective intramolecular [5+2] cycloaddition to rapidly assemble the unique [6,7,5] spirotricyclic skeleton; (3) sequential installation of the requisite alkyl groups and alkenes present in the targeted molecule by leveraging the functionalities positioned on the tricycle; (4) Fe‐catalyzed hydrogen atom transfer (HAT)‐initiated hydrogenation to stereospecifically reduce the tetrasubstituted Δ 10,11 olefin and install the contiguous stereocenters; (5) Fe‐mediated HAT‐initiated 3‐ exo ‐ trig radical cyclization to rapidly forge the tetrasubstituted cyclopropane ring with excellent stereoselectivity.