Theoretical study on the mechanism of iridium-catalyzed γ-functionalization of primary alkyl C–H bonds

The mechanism of the iridium-catalyzed functionalization of a primary C–H bond at the γ position of an alcohol 5 is investigated by density functional theory (DFT) calculations. A new IrIII–IrV mechanism is found to be more feasible than the previously reported IrI–IrIII mechanism. 10 In the IrIII–IrV mechanism, the reaction begins with the initial formation of (Me4phen)IrIII(H)[Si(OR)Et2]2 from the catalyst precursor, [Ir(cod)OMe]2 (cod = 1,5-cyclooctadiene). The catalytic cycle includes five steps: (1) the insertion of norbornene into the Ir–H bond to produce (Me4phen)IrIII(norbornyl)[Si(OR)Et2]2 (R = –CH(C2H5)C3H7); (2) the Si–H oxidative addition of HSi(OR)Et2 to form (Me4phen)IrVH(norbornyl)[Si(OR)Et2]3; (3) the reductive elimination of norbornane to furnish (Me4phen)IrIII[Si(OR)Et2]3; (4) the intramolecular C–H activation of the primary C–H bond at the γ position; and (5) the Si–C reductive elimination to produce the final product and regenerate the catalyst. The highest barrier in the IrIII–IrV mechanism is 7.3 kcal/mol lower than that of the IrI–IrIII mechanism. In addition, the regioselectivity of the C–H activation predicted by this new IrIII–IrV mechanism is consistent with experimental observation.