Davis Christopher W, Zhang Yu, Li Yanrong, Martinelli Matteo, Zhang Jingyang, Ungarean Chad, Galer Petra, Liu Peng, Sarlah David
Department of Chemistry, University of Illinois, Urbana, IL 61801, USA.
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Angew Chem Int Ed Engl. 2024 Aug 5;63(32):e202407281. doi: 10.1002/anie.202407281. Epub 2024 Jul 16.
Catalytic olefin hydroamination reactions are some of the most atom-economical transformations that bridge readily available starting materials-olefins and high-value-added amines. Despite significant advances in this field over the last two decades, the formal hydroamination of nonactivated aromatic compounds remains an unsolved challenge. Herein, we report the extension of olefin hydroamination to aromatic π-systems by using arenophile-mediated dearomatization and Cu-catalysis to perform 1,2-hydroamination on nonactivated arenes. This strategy was applied to a variety of substituted arenes and heteroarenes to provide general access to structurally complex amines. We conducted DFT calculations to inform mechanistic understanding and rationalize unexpected selectivity trends. Furthermore, we developed a practical, scalable desymmetrization to deliver enantioenriched dearomatized products and enable downstream synthetic applications. We ultimately used this dearomative strategy to efficiently synthesize a collection of densely functionalized small molecules.
催化烯烃氢胺化反应是一些最具原子经济性的转化反应，它们连接了易于获得的起始原料——烯烃和高附加值的胺。尽管在过去二十年中该领域取得了重大进展，但非活化芳香族化合物的形式氢胺化仍然是一个未解决的挑战。在此，我们报道了通过亲芳基介导的去芳构化和铜催化，将烯烃氢胺化扩展到芳香π体系，以对非活化芳烃进行1,2-氢胺化。该策略应用于各种取代芳烃和杂芳烃，以提供获得结构复杂胺的通用方法。我们进行了密度泛函理论（DFT）计算，以增进对机理的理解并合理化意外的选择性趋势。此外，我们开发了一种实用、可扩展的去对称化方法，以提供对映体富集的去芳构化产物并实现下游合成应用。我们最终利用这种去芳构化策略高效合成了一系列高度官能化的小分子。
