摘要：Jonas Düker, Nele Petersen, Noah Richter, Paul Feuerer, Teresa Faber, Niklas Hölter, Niklas Kehl, Jan Oboril, Julian Strippel, Al
转自：康龙化成
Room-Temperature Copper Cross-Coupling Reactions of Anilines with Aryl Bromides
Jonas Düker, Nele Petersen, Noah Richter, Paul Feuerer, Teresa Faber, Niklas Hölter, Niklas Kehl, Jan Oboril, Julian Strippel, Alexander Gröer, Nicolas Guimond, Sherif J. Kaldas, Maximilian Lübbesmeyer, Giulio Volpin, Burkhard König,* and Julius Hillenbrand*
FakultätfürChemie und Pharmazie, Universität Regensburg, 93053 Regensburg, Germany;
Bayer AG, Pharmaceuticals, 42117 Wuppertal, Germany;
—Org. Lett. 2025. doi.org/10.1021/acs.orglett.5c00699.
Recommended by Shi Li_MOC
KEYWORDS:C-N Coupling, Cu Catalysis (反应类型), Aryl Bromides,Aryl Chlorides, Anilines (原料), Biaryl Amines (产物), C(sp2)-N (成键类型), 6-hydroxy picolinhydrazide ligand,Room-Temperature (其他)
ABSTRACT:The authors present a novel copper-catalyzed method for aniline cross-couplings promoted by a 6-hydroxy picolinhydrazideligand. The method achieves room-temperature reactivity with aryl bromides, enabled by a methanol/ethanol solvent mixture and a mild, functional group-compatible base, with catalyst loadings as low as 0.5 mol %. The use of industrially preferred solvents and base, as well as the high catalytic activity, offers a significant advancement in the practicality and scalability of industrial processes. Furthermore, the approach extends to the cross-coupling of aryl chlorides under elevated temperatures and demonstrates compatibility with additional nucleophile classes.
Background
This Work
Optimization of Reaction Conditions
Substrate
Scope with Aryl Bromides
Substrate Scope with Aryl Chlorides
Scope of Additional Nucleophiles
Julius Hillenbrand et al. have developed a method for copper-catalyzed cross-coupling of anilines with aryl bromides at room-temperature utilizing a 6-hydroxypicolinhydrazide ligand. The method demonstrates broad compatibility with structurally diverse coupling partners and achieves efficient coupling with minimal catalyst loadings of 0.5 mol% using an industrially preferred base and solvents. The beneficial role of methanol as a solvent in copper catalysis is expected to inspire further investigation. Additionally, the reaction conditions are adaptable to the coupling of aryl chlorides at elevated temperatures using an alternative alcohol solvent, as well as to other nucleophile classes.
来源：新浪财经
