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 [H2Ir(py-N(Me)CH)L2]BF4 (2a) via cyclometalation, H2 loss, and reversible α-elimination. Agostic intermediate
[H2Ir(py-N(Me)CH2H)L2]BF4 (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(OCMe2)(py-N(Me)CH2)L2]BF4 (3aMe2CO), 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 3cCO, 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 (ΔG)
surfaces to allow fast catalysis.