Mechanistic study of the selectivity of olefin versus cyclobutene formation by palladium(0)-catalyzed intramolecular C(sp3)-H activation.

This study describes the mechanism and selectivity pattern of the Pd(0)-catalyzed C(sp(3))-H activation of a prototypical substrate bearing two linear alkyl groups. Experimentally, the use of the Pd/P(t-Bu)3 catalytic system leads to a ca. 7:3 mixture of olefin and benzocyclobutene (BCB) products. The C-H activation step was computed to be favored for the secondary position α to the benzylic carbon over the primary position β to the benzylic carbon by more than 4 kcal mol(-1), in line with previous selectivity trends on analogous substrates. The five-membered palladacycle obtained through this activation step may then follow two different pathways, which were computationally characterized: (1) decoordination of the protonated base and reductive elimination to give the BCB product and (2) proton transfer to the aryl ligand and base-mediated β-H elimination to give the olefin product. Experiments conducted with deuterated substrates were in accordance with this mechanism. The difference between the highest activation barriers in the two pathways was computed to be 1.2 kcal mol(-1) in favor of BCB formation. However, the use of a kinetic model revealed the critical influence of the kinetics of dissociation of HCO3(-) formed after the C-H activation step in actually directing the reaction toward either of the two pathways.