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We developed a method for synthesizing aryl alkyl thioether compounds via a three-component reaction involving aryldiazonium salts, 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide), and alkyl bromides. Optimal yields were achieved when a copper catalyst was used in conjunction with zinc and tetrabutylammonium bromide in an acetonitrile solvent at 130 °C for 10 h. This methodology demonstrates good functional group tolerance and enables the successful synthesis of various aryl alkyl thioethers with moderate to high yields.
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http://dx.doi.org/10.1021/acs.joc.4c01611 | DOI Listing |
J Am Chem Soc
September 2025
Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, P. R. China.
The direct cross-coupling of unactivated alkyl halides with aryl or heteroaryl partners remains a fundamental challenge in synthetic chemistry due to their inertness and propensity for side reactions. Herein, we report a transition-metal-free electrochemical halogen-atom transfer strategy that enables efficient alkyl radical cross-coupling via convergent paired electrolysis. In this system, anodically generated α-aminoalkyl radicals mediate the activation of alkyl iodides, while aryl/heteroaryl aldehydes or nitriles undergo cathodic reduction to afford persistent ketyl radical anions or aryl radical anions.
View Article and Find Full Text PDFOrg Lett
September 2025
School of Molecular Sciences, The University of Western Australia, Crawley, WA 6009, Australia.
We report the synthesis of three nickel complexes based on Ni(NHC)[P(OR)](Ar)Cl and their application in C()-N cross-coupling reactions. Reactions involving secondary amines proceeded at room temperature, while anilines and primary alkyl amines coupled under mild heating. The reported complexes are air-stable as solids, operate at low catalytic loading, and do not require an exogenous ligand.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
September 2025
Shenzhen Grubbs Institute, Department of Chemistry, Guangming Advanced Research Institute, and Shenzhen Key Laboratory of Cross-Coupling Reactions, Southern University of Science and Technology, Shenzhen, 518055, China.
Despite the widespread utility of transition metal-catalyzed cross-couplings in organic synthesis, the coupling of unactivated alkyl electrophiles remains challenging due to sluggish oxidative addition and competing side reactions. Here, we describe a general and practical copper-catalyzed radical deoxyalkynylation of α-unfunctionalized alcohols through a synergistic combination of Barton-McCombie deoxygenation and copper-catalyzed radical cross-coupling. Key to the success of this method lies in not only the development of rigid anionic multiple N,N,N-ligand to exert remarkable selectivity of highly reactive unactivated alkyl radicals, but also the selection of one suitable oxidant to suppress Glaser homocoupling and other side products.
View Article and Find Full Text PDFJ Am Chem Soc
September 2025
Shenzhen Key Laboratory of Cross Coupling Reactions & Department of Chemistry, Southern University of Science and Technology (SUSTech), Shenzhen 518055, China.
Currently, most sulfoximine clinical candidates feature both -aryl and -alkyl substituents. The asymmetric synthesis of these compounds typically relies on oxidizing corresponding enantioenriched sulfilimines. Herein, we describe an effective catalytic system comprising CuI and an azabicyclo[2.
View Article and Find Full Text PDFJ Am Chem Soc
September 2025
Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, California 90095, United States.
Bipyridine-ligated nickel(I) and nickel(0) intermediates are widely proposed in Ni-catalyzed cross-coupling reactions. However, few isolable Ni and Ni complexes with catalytically relevant bipyridine ligands are known, limiting our understanding of these complexes' speciation and reactivity. In this work, we identify and investigate well-defined, isolable (bpy)Ni and (bpy)Ni complexes to characterize their behavior in catalytic systems.
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