In Situ Kinetic Studies of Rh(II)-Catalyzed C–H Functionalization to Achieve High Catalyst Turnover Numbers
Bo Wei, Jack C. Sharland, Donna G. Blackmond, Djamaladdin G. Musaev, Huw M. L. Davies
Abstract
Detailed kinetic studies on the functionalization of unactivated hydrocarbon sp3 C–H bonds by dirhodium-catalyzed reaction of aryldiazoacetates revealed that the C–H functionalization step is rate determining. The efficiency of this step was increased by using the hydrocarbon as a solvent and using donor/acceptor carbenes with an electron-withdrawing substituent on the aryl donor group. The optimum catalyst for these reactions is the tetraphenylphthalimido derivative Rh2(R-TPPTTL)4, and a further beneficial refinement was obtained by using N,N′-dicyclohexylcarbodiimide as an additive. Under the optimum conditions with a catalyst loading of 0.001 mol %, effective enantioselective C–H functionalization (66–97% yield, 83–97% ee) of cycloalkanes was achieved with a range of aryldiazoacetates as long as the aryldiazoacetate was not sterically demanding. The reaction with cyclohexane using a catalyst loading of 0.0005 mol % could be recharged twice with additional aryldiazoacetate, resulting in an overall dirhodium catalyst turnover number of 580,000.