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

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(η 6 -C 7 H 8 )][BAr F 4 ] (dcype = 1,2-bis(dicyclohexylphosphino)ethane; BAr F 4 = B[(3,5-(CF 3 ) 2 )C 6 H 3 ] 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 η 6 -arene complexes supported a pathway involving C( sp 2 )-H activation from a cobalt(III) metallacycle.