DFT Mechanistic Investigation of an Enantioselective Tsuji–Trost Allylation Reaction

A comprehensive
mechanistic examination of an asymmetric palladium-catalyzed Tsuji–Trost
allylation reaction that identifies the enantioselective step was
completed utilizing DFT computational tools and the nudged elastic
band method. Key components of the study include (a) plausible reaction
pathways for the full interconversion of a square-planar palladium
allyl enolate intermediate with low barriers relative to the subsequent
enantioselectivity-determining reductive C–C coupling step,
thereby disputing the previously identified mechanism, (b) a detailed
analysis of the factors influencing the stereochemical control involved
in forming the preferred configuration via the reductive C–C
coupling step, (c) a comprehensive examination of the competing outer-sphere
mechanism that includes a metal counterion as an escort to the nucleophile
in order to modulate the effects of modeling the reaction step of
oppositely charged species, and (d) examination of the possible role
water plays in stabilizing a keto-coordinated adduct of PdII-η1-allyl, formed early in the catalytic cycle,
relative to a carboxylate-coordinated adduct, the known resting state
of the reaction. Barrier energies for the enantioselective C–C
coupling are investigated with several levels of theory, and together
they support a reaction mechanism consistent with the preferred formation
of the correct enantiomer on the basis of the enantiomer of the ligand
selected.