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((NBuPPh2)-Bu-t)(2)Pd(eta(3)-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)((NBuPPh2)-Bu-t)(2)Pd(eta(3)-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 10(5). The Pd-Ti distance in 1 is the result of the (NBu)-Bu-t groups enforcing a boat conformation that brings the two metals into dose proximity, especially in the transition state. The turnover frequency of classic Pd pi 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)(2)Pd(eta(3)-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.