Pd Species Mediation in Pd-Catalyzed Direct Alkylation of Arenes with Oxiranes: A DFT Study.

The reaction mechanisms of Pd(OAc)-catalyzed dehydrogenative alkylation of 2-phenylpyridine with oxirane were investigated using DFT calculations. The most plausible reaction pathway was confirmed as a Pd catalytic cycle consisting of four processes: C-H activation, ring-opening oxidative addition of oxirane, reductive elimination, and recovery of the catalyst. According to the B2PLYP/DGDZVP computational data, the oxidative addition of oxirane for converting Pd to Pd was assigned to be the rate-determining step with a free-energy barrier of 28.1 kcal·mol. For comparison, we also studied the alternative Pd-only pathway without a change of oxidation state and found that it was hindered kinetically by a high free-energy barrier of 75.1 kcal·mol occurring for the ring-opening migratory insertion of oxirane. In addition, the small-ring strain of oxirane should be responsible for the feasible C-O bond-cleavage and subsequent Pd → Pd conversion, because the designed four-, five-, and six-membered-ring reagents did not display such an oxidative addition reactivity. Lastly, an extended reactivity order among oxirane, PhI, PhBr, and PhCl toward oxidative addition onto Pd to form Pd was proposed in this article based on the computed kinetic parameters.