Three-Component Coupling of Arenes, Ethylene, and Alkynes Catalyzed by a Cationic Bis(phosphine) Cobalt Complex: Intercepting Metallacyclopentenes for C–H Functionalization

• Published in: Journal of the American Chemical Society Vol. 144; no. 10; pp. 4530 - 4540
• Main Authors: Whitehurst, William G, Kim, Junho, Koenig, Stefan G, Chirik, Paul J
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 16.03.2022; Amer Chemical Soc
• Subjects: Alkynes; aromatic hydrocarbons; carbon-hydrogen bond activation; Catalysis; Cations; Chemistry; Chemistry, Multidisciplinary; Cobalt; deuterium; ethane; ethylene; Ethylenes; fenofibrate; haloperidol; Molecular Structure; phosphine; Phosphines; Physical Sciences; Science & Technology; ALKENES; CYCLOADDITION; ACTIVATION; 1,6-ENYNES; HYDROBORATION/CYCLIZATION; N-H; METAL; HYDROARYLATIONS; METALLOCYCLES; ENYNES
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/jacs.1c12646

A cobalt-catalyzed intermolecular three-component coupling of arenes, ethylene, and alkynes was developed using the well-defined air-stable cationic bis­(phosphine) cobalt­(I) complex, [(dcype)­Co­(η6-C7H8)]­[BArF 4] (dcype = 1,2-bis­(dicyclohexylphosphino)­ethane; BArF 4 = B­[(3,5-(CF3)2)­C6H3]4), as the precatalyst. All three components were required for turnover and formation of ortho-homoallylated arene products. A range of directing groups including amide, ketone, and 2-pyridyl substituents on the arene promoted the reaction. The cobalt-catalyzed method exhibited broad functional group tolerance allowing for the late-stage functionalization of two drug molecules, fenofibrate and haloperidol. A series of control reactions, deuterium labeling studies, resting state analysis, as well as synthesis of substrate- and product-bound η6-arene complexes supported a pathway involving C­(sp 2 )–H activation from a cobalt­(III) metallacycle.