Catalysis with a Skip: Dynamically Coupled Addition, Proton Transfer, and Elimination during Au- and Pd-Catalyzed Diol Cyclizations

Au and Pd complexes have emerged
as highly effective π-bond
cyclization catalysts to construct heterocycles. These cyclization
reactions are generally proposed to proceed through multistep addition–elimination
mechanisms involving Au– or Pd–alkyl intermediates.
For Au- and Pd-catalyzed allylic diol cyclizations, while the density
functional theory (DFT) potential energy surface landscapes show a
stepwise sequence of alkoxylation π-addition, proton transfer,
and water elimination, quasiclassical direct dynamics simulations
reveal dynamical mechanisms that depend on the metal center. For Au,
trajectories reveal that after π-addition the Au–alkyl
intermediate is always skipped because addition is dynamically coupled
with proton transfer and water elimination. In contrast, for Pd catalysis,
due to differences in the potential energy landscape shape, only about
half of trajectories show Pd–alkyl intermediate skipping. The
other half of the trajectories show the traditional two-step mechanism
with the intervening Pd–alkyl intermediate. Overall, this work
reveals that interpretation of a DFT potential energy landscape can
be insufficient to understand catalytic intermediates and mechanisms
and that atomic momenta through dynamics simulations are needed to
determine if an intermediate is genuinely part of a catalytic cycle.