College of Chemical Engineering, State Key Laboratory Breeding Base of Green-Chemical Synthesis Technology, Zhejiang University of Technology, Hangzhou, 310014, China.
Department of Chemistry, Zhejiang University, Hangzhou, 310058, China.
Nat Commun. 2020 Sep 1;11(1):4380. doi: 10.1038/s41467-020-18137-w.
Dearomative functionalization reactions represent an important strategy for the synthesis of valuable three-dimensional molecules from simple planar aromatics. Naphthalene is a challenging arene towards transition-metal-catalyzed dearomative difunctionalization reactions. Reported herein is an application of naphthalene as a masked conjugated diene in a palladium-catalyzed dearomative 1,4-diarylation or 1,4-vinylarylation reaction via tandem Heck/Suzuki sequence. Three types of 1,4-dihydronaphthalene-based spirocyclic compounds are achieved in excellent regio- and diastereoselectivities. Key to this transformation is the inhibition of a few competitive side reactions, including intramolecular naphthalenyl C-H arylation, intermolecular Suzuki cross-coupling, dearomative 1,2-difunctionalization, and dearomative reductive-Heck reaction. Density functional theory (DFT) calculations imply that the facile exergonic dearomative insertion of a naphthalene double bond disrupts the sequence of direct Suzuki coupling, leading to the tandem Heck/Suzuki coupling reaction. The observed regioselectivity towards 1,4-difunctionalization is due to the steric repulsions between the introduced aryl group and the spiro-scaffold in 1,2-difunctionalization.
去芳构官能化反应是从简单的平面芳烃合成有价值的三维分子的重要策略。萘是一种具有挑战性的芳环，难以进行过渡金属催化的去芳构双官能化反应。本文报道了一种将萘作为掩蔽共轭二烯应用于钯催化的去芳构 1,4-二芳基化或 1,4-乙烯基芳基化反应的方法，通过串联 Heck/Suzuki 序列实现。通过优异的区域和立体选择性，实现了三种基于 1,4-二氢萘的螺环化合物。实现这一转变的关键是抑制几种竞争的副反应，包括分子内萘基 C-H 芳基化、分子间 Suzuki 交叉偶联、去芳构 1,2-双官能化和去芳构还原 Heck 反应。密度泛函理论（DFT）计算表明，萘双键的易进行的放能去芳构插入破坏了直接 Suzuki 偶联的顺序，导致串联 Heck/Suzuki 偶联反应。观察到的 1,4-双官能化的区域选择性归因于在 1,2-双官能化中引入的芳基与螺骨架之间的空间排斥。
