Mechanistic Study of the Selectivity
of Olefin versus
Cyclobutene Formation by Palladium(0)-Catalyzed Intramolecular C(sp<sup>3</sup>)–H Activation
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Abstract
This
study describes the mechanism and selectivity pattern of the
Pd<sup>0</sup>-catalyzed C(sp<sup>3</sup>)–H activation of
a prototypical substrate bearing two linear alkyl groups. Experimentally,
the use of the Pd/P(<i>t</i>-Bu)<sub>3</sub> 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<sup>–1</sup>, 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<sup>–1</sup> in favor of BCB formation. However, the use
of a kinetic model revealed the critical influence of the kinetics
of dissociation of HCO<sub>3</sub><sup>–</sup> formed after
the C–H activation step in actually directing the reaction
toward either of the two pathways