Reaction mechanism, norbornene and ligand effects, and origins of: Meta -selectivity of Pd/norbornene-catalyzed C-H activation

The reaction mechanism, ligand and norbornene effects, and origins of meta-selectivity in Pd/norbornene-catalyzed alkylation and arylation via C-H activation are theoretically elucidated by DFT computation. The reaction proceeds through six major steps: ortho-C-H activation, norbornene insertion into Pd-C bonds, meta-C-H activation, meta-C-C bond formation, β-carbon elimination, and protodemetallation. Both ortho-C-H and meta-C-H activations undergo a concerted metalation-deprotonation pathway. The meta-C-C bond formation, which is the selectivity-determining step, follows a Pd(iv) pathway via oxidative addition on a Pd(ii) five-membered-ring intermediate. The oxidative addition of alkyl iodide adopts an S_N2 pathway, whereas aryl iodide prefers concerted oxidative addition rather than the S_N2 pathway. The Pd(ii) pathway via meta-C-C reductive coupling on dinuclear palladium species is not the dominant pathway because of the low concentration of Pd(0)L₂. For methylation, with norbornene and pyridine (or its derivative) as ligands, the C-C reductive coupling and C-C reductive elimination from the Pd(iv) intermediate are found to be the selectivity-determining steps for meta-functionalization and benzocyclobutene formation, respectively, whereas the use of large ligands such as acridine and quinoline-type ligands (L1 and L2) moves the selectivity-determining step back to the oxidative addition and the C-C reductive elimination steps on the Pd(ii) intermediate. The geometric and electronic properties of L1 and L2 further suppress the benzocyclobutene formation by increasing the energy difference between meta-functionalization and benzocyclobutene formation. The combination of 2-carbomethoxynorbornene and L2 promotes meta-ethylation and -arylation by disfavoring the C-C reductive elimination steps from the Pd(ii) and Pd(iv) intermediates as well as slightly favoring the oxidative addition step.