Wang Yun-Peng, Fang Kun, Tu Yong-Qiang, Yin Jun-Jie, Zhao Qi, Ke Tian
School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, Shanghai, 200240, China.
State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China.
Nat Commun. 2022 Apr 28;13(1):2335. doi: 10.1038/s41467-022-29947-5.
A modular and efficient method for constructing angular tri-carbocyclic architectures containing quaternary carbon center(s) from 1,3-dicycloalkylidenyl ketones is established, which involves an unconventional synergistic cascade of a Nazarov cyclization and two ring expansions. It features high selectivity, mild conditions and convenient operation, wide scope and easy availability of substrate. Substitution with R and R at the 4πe-system with electron-donating group favors this reaction, while that with electron-withdrawing group or proton disfavors. The electron-donating group as R directs the initial ring expansion at its own site, while the p-π- or n-π- associated substituent as R favors selectively the later ring expansion near its location because of the beneficial maintenance of an original conjugated system. The stereoselectivity has proved to be governed by either the steric effect of R and R at the expanded rings, or the migration ability of the migrating atom. Density Functional Theory calculation suggests the initial Nazarov cyclization would be the rate-determining step. A racemic total synthesis of the natural (±)-waihoensene is realized in 18 steps by use of this methodology.
建立了一种由1,3-二环亚烷基酮构建含季碳中心的角型三环碳环结构的模块化高效方法，该方法涉及Nazarov环化反应和两次环扩张的非常规协同串联反应。其特点是选择性高、条件温和、操作简便、底物适用范围广且易于获得。在4πe-体系中，用供电子基团取代R和R有利于该反应，而用吸电子基团或质子取代则不利于反应。作为R的供电子基团在其自身位置引导初始环扩张，而作为R的p-π或n-π相关取代基由于有利于维持原始共轭体系而选择性地促进其附近的后续环扩张。立体选择性已证明受扩张环上R和R的空间效应或迁移原子的迁移能力控制。密度泛函理论计算表明，初始的Nazarov环化反应是速率决定步骤。利用该方法，通过18步实现了天然（±）-waihoensene的外消旋全合成。
