Silver-catalyzed formal [2π+2σ] cycloaddition of bicyclobutanes with naphthols as surrogates for arynes

The [2π+2σ] cycloaddition reaction between bicyclobutanes (BCBs) and C=X (where X = C or heteroatom) coupling partners is a reliable method to efficiently construct (hetero)bicyclo[2.1.1]hexane (BCH) frameworks. However, similar reactions involving C≡C triple bonds for synthesizing valuable bicyclo[2.1.1]hexenes (BCHes), particularly with arynes, are extremely rare due to the competing favorable Alder-Ene reaction. Here we report a silver-catalyzed dearomative [2π+2σ] cycloaddition/rearomatization strategy for the modular synthesis of functionalized benzobicyclo[2.1.1]hexene derivatives (Benzo-BCHes). Using AgBF4 as the catalyst and with naphthols serving as surrogates for arynes, the reaction proceeded with high chemoselectivity to generate Benzo-BCHs, achieving up to 83% yield despite competing with at least five side reactions. The protocol exhibits a broad substrate scope, excellent functional group tolerance, versatile functionalization of the products, and scalable synthesis, thereby underscoring its practical utility for the construction of complex Benzo-BCH structures. Density functional theory (DFT) computations offer mechanistic insights into the cycloaddition/rearomatization process, and aromaticity modulation in annelated naphthalenes, and elucidate the origin of observed chemoselectivity.

双环丁烷（bicyclobutanes, BCBs）与C=X（X为碳或杂原子）偶联底物之间的[2π+2σ]环加成反应，是高效构建（杂）双环[2.1.1]己烷（(hetero)bicyclo[2.1.1]hexane, BCH）骨架的可靠方法。然而，以碳-碳三键为底物合成具有应用价值的双环[2.1.1]己烯（bicyclo[2.1.1]hexenes, BCHes）的类似反应，尤其是涉及芳炔的此类反应，却极为罕见——这源于竞争性的优势阿尔德-烯（Alder-Ene）反应的存在。本文报道了一种银催化的脱芳构化[2π+2σ]环加成/再芳构化策略，用于模块化合成官能化苯并双环[2.1.1]己烯衍生物（benzobicyclo[2.1.1]hexene derivatives, Benzo-BCHes）。该反应以四氟硼酸银（AgBF4）为催化剂，以萘酚（naphthols）作为芳炔的替代底物，展现出优异的化学选择性，可生成苯并双环[2.1.1]己烷类产物；尽管存在至少五种竞争副反应，该方法的最高产率仍可达83%。该合成策略具备宽泛的底物适用范围、极佳的官能团耐受性，产物可进行多样化官能化修饰，且可实现规模化合成，从而凸显了其在构建复杂苯并双环[2.1.1]己烷类结构中的实用价值。密度泛函理论（density functional theory, DFT）计算为该环加成/再芳构化过程、稠合萘环的芳香性调控机制提供了深入见解，并阐明了观测到的化学选择性的起源。