Origin of Fast Catalysis in Allylic Amination Reactions Catalyzed by Pd–Ti Heterobimetallic Complexes

Experiments and density functional calculations were used to quantify the impact of the Pd–Ti interaction in the cationic heterobimetallic Cl2Ti­(NtBuPPh2)2Pd­(η3-methallyl) catalyst 1 used for allylic aminations. The catalytic significance of the Pd–Ti interaction was evaluated computationally by examining the catalytic cycle for catalyst 1 with a conformation where the Pd–Ti interaction is intact versus one where the Pd–Ti interaction is severed. Studies were also performed on the relative reactivity of the cationic monometallic (CH2)2(NtBuPPh2)2Pd­(η3-methallyl) catalyst 2 where the Ti from catalyst 1 was replaced by an ethylene group. These computational and experimental studies revealed that the Pd–Ti interaction lowers the activation barrier for turnover-limiting amine reductive addition and accelerates catalysis up to 105. The Pd–Ti distance in 1 is the result of the NtBu groups enforcing a boat conformation that brings the two metals into close proximity, especially in the transition state. The turnover frequency of classic Pd π allyl complexes was compared to that of 1 to determine the impact of P–Pd–P coordination angle and ligand electronic properties on catalysis. These experiments identified that cationic (PPh3)2Pd­(η3-CH2C­(CH3)­CH2) catalyst 3 performs similarly to 1 for allylic aminations with diethylamine. However, computations and experiment reveal that the apparent similarity in reactivity is due to very fast reaction kinetics. The higher reactivity of 1 versus 3 was confirmed in the reaction of methallyl chloride and 2,2,6,6-tetramethylpiperidine (TMP). Overall, experiments and calculations demonstrate that the Pd–Ti interaction induces and is responsible for significantly lower barriers and faster catalysis for allylic aminations.