In-situ Kinetic Studies of Rh(II)-Catalyzed C-H Functionalization to Achieve High Catalyst Turnover Numbers.

Detailed kinetic studies on the functionalization of unactivated hydrocarbon sp 3 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 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) was achieved of cycloalkanes with a range of aryldiazoacetates as long as the aryldiazoacetate was not to 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.