Double geminal C-H activation and reversible α-elimination in 2-aminopyridine iridium(III) complexes: The role of hydrides and solvent in flattening the free energy surface

[H₂Ir(OCMe₂)₂L₂]BF₄ (1) (L = PPh₃), a preferred catalyst for tritiation of pharmaceuticals, reacts with model substrate 2-(dimethylamino)pyridine (py-NMe₂; py = 2-pyridyl) to give chelate carbene [H ₂Ir(py-N(Me)CH=)L₂]BF₄ (2a) via cyclometalation, H₂ loss, and reversible α-elimination. Agostic intermediate [H₂Ir(py-N(Me)CH₂-H)L₂]BF ₄ (4a), seen by NMR, is predicted (DFT(B3PW91) computations) to give C-H oxidative addition to form the alkyl intermediate [(H)(η²- H₂)Ir(py-N(Me)CH₂-)L₂]BF₄. Loss of H₂ leads to the fully characterized alkyl [HIr(OCMe ₂)(py-N(Me)CH₂-)L₂]BF₄ (3a ^Me2CO), which loses acetone to give alkylidene hydride 2a by rapid reversible α-elimination. 2a rapidly reacts with excess H₂ in d₆-acetone to generate [H₂Ir(OC(CD₃) ₂)₂L₂]BF₄ (1-d₁₂), 3a^(CD3)2CO, and py-NMe₂ in a 1:1:1 ratio, showing reversibility and accounting for the selective isotope exchange catalyzed by 1. Reaction of 1 with py-N(CH₂)₄ gives the fully characterized carbene 2c. A cis-L₂ carbene intermediate, cis-2c, observed by NMR, reacts with CO via retro α-elimination to give the alkyl 3c^CO, while the trans isomer, 2c, does not react; retro α-elimination thus requires the Ir-H bond to be orthogonal to the carbene plane. Consistent with experiment, computational studies show a particularly flat PE surface with activation of the agostic C-H bond giving a less stable H₂ complex, then formation of a kinetic carbene complex with cis-L, only seen experimentally for py-N(CH₂)₄. Hydrides at key positions, together with gain or loss of solvent and H₂, flatten the PE (AG) surfaces to allow fast catalysis.