For nearly 60 years, significant research efforts have been focused on developing strategies for the cycloaddition of bicyclobutanes (BCBs). However, higher-order cycloaddition and catalytic asymmetric cycloaddition of BCBs have been long-standing formidable challenges. Here, we report Pd-catalyzed ligand-controlled, tunable cycloadditions for the divergent synthesis of bridged bicyclic frameworks. The dppb ligand facilitates the formal (5+3) cycloaddition of BCBs and vinyl oxiranes, yielding valuable eight-membered ethers with bridged bicyclic scaffolds in 100% regioselectivity. The Cy-DPEphos ligand promotes selective hetero-[2σ+2σ] cycloadditions to access pharmacologically important 2-oxabicyclo[3.1.1]heptane (O-BCHeps). Furthermore, the corresponding catalytic asymmetric synthesis of O-BCHeps with 94–99% ee has been achieved using chiral (S)-DTBM-Segphos, representing the first catalytic asymmetric cross-dimerization of two strained rings. The obtained O-BCHeps are promising bioisosteres for ortho-substituted benzenes.

中文翻译：

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钯催化配体控制的可切换杂-(5 + 3)/对映选择性 [2σ+2σ] 双环丁烷与乙烯基环氧乙烷的环加成

近 60 年来，大量的研究工作一直集中在开发双环丁烷 (BCB) 环加成策略上。然而，BCB 的高阶环加成和催化不对称环加成一直是长期存在的艰巨挑战。在这里，我们报道了 Pd 催化的配体控制的、可调节的环加成反应，用于桥联双环骨架的不同合成。 dppb 配体促进 BCB 和乙烯基环氧乙烷的正式 (5+3) 环加成，以 100% 区域选择性产生具有桥联双环支架的有价值的八元醚。 Cy-DPEphos 配体促进选择性杂-[2σ+2σ] 环加成，以获得药理学上重要的 2-氧杂双环[3.1.1]庚烷 (O-BCHeps)。此外，使用手性 ( S )-DTBM-Segphos实现了相应的催化不对称合成 ee 为 94-99% 的 O-BCHeps ，这代表了两个应变环的首次催化不对称交叉二聚。获得的 O-BCHeps 是有前途的邻位取代苯的生物等排体。