Medium-sized rings, including those embedded in bridged and fused bicyclic scaffolds, are common core structures of myriad bioactive molecules. Among various synthetic strategies towards their synthesis, intermolecular higher-order cycloaddition provides great potential to build complex medium-sized rings from simple building blocks. Unfortunately, such transformations are often plagued with competitive reaction pathways and low levels of site- and stereoselectivity. Herein, we report catalyst-controlled divergent access to three classes of medium-sized bicyclic compounds in high efficiency and stereoselectivity, by palladium-catalysed cycloadditions of tropones with γ-methylidene-δ-valerolactones. Mechanistic studies and density functional theory calculations disclosed that the divergent reactions stem from the different reaction profiles of the diastereomeric intermediates. While one undergoes either O- or C-allylation to provide [5.5.0] or [4.4.1] bicyclic compounds, the unique conformation of the other diastereomer allows an unconventional alkene isomerization to deliver bridgehead alkene-containing bicyclo[4.4.1] compounds. The conversion of these products to diverse complex polycyclic scaffolds has also been demonstrated.

中型环，包括嵌入桥接和稠合双环支架中的环，是无数生物活性分子的常见核心结构。在各种合成策略中，分子间的高阶环加成具有巨大的潜力，可以从简单的结构单元中构建复杂的中型环。不幸的是，这种转化常常受到竞争性反应途径和低水平的位点和立体选择性的困扰。在本文中，我们报道了钯催化的tropones与γ-亚甲基-δ-戊内酯的环加成反应，从而控制了三类中型双环化合物的催化控制的发散性。机理研究和密度泛函理论计算表明，发散反应源于非对映异构中间体的不同反应谱。当一个化合物进行O-或C-烯丙基化以提供[5.5.0]或[4.4.1]双环化合物时，另一种非对映异构体的独特构型允许非常规的烯烃异构化，从而提供含桥头烯烃的双环化合物[4.4.1]。化合物。还证明了这些产物向多种复杂的多环支架的转化。