Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706, USA.
Cherry L. Emerson Center for Scientific Computation, Emory University, 1515 Dickey Drive, Atlanta, GA 30322, USA.
Science. 2020 Dec 18;370(6523):1454-1460. doi: 10.1126/science.abd1085. Epub 2020 Nov 19.
Palladium(II)-catalyzed carbon-hydrogen (C-H) oxidation reactions could streamline the synthesis of pharmaceuticals, agrochemicals, and other complex organic molecules. Existing methods, however, commonly exhibit poor catalyst performance with high palladium (Pd) loading (e.g., 10 mole %) and a need for (super)stoichiometric quantities of undesirable oxidants, such as benzoquinone and silver(I) salts. The present study probes the mechanism of a representative Pd-catalyzed oxidative C-H arylation reaction and elucidates mechanistic features that undermine catalyst performance, including substrate-consuming side reactions and sequestration of the catalyst as an inactive species. Systematic tuning of the quinone cocatalyst overcomes these deleterious features. Use of 2,5-di--butyl--benzoquinone enables efficient use of molecular oxygen as the oxidant, high reaction yields, and >1900 turnovers by the Pd catalyst.
钯（II）催化的碳-氢键（C-H）氧化反应可以简化药物、农用化学品和其他复杂有机分子的合成。然而，现有的方法通常表现出较差的催化剂性能，需要高钯（Pd）负载（例如 10 摩尔％）和大量不需要的氧化剂（如苯醌和银（I）盐）。本研究探讨了代表性的钯催化氧化 C-H 芳基化反应的机理，并阐明了破坏催化剂性能的机理特征，包括消耗底物的副反应和催化剂作为非活性物质的隔离。醌类共催化剂的系统调谐克服了这些有害特征。使用 2,5-二-叔丁基-苯醌可以有效地使用分子氧作为氧化剂，实现高反应收率和 Pd 催化剂的 >1900 次周转。
