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 Pd II -η 1 -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.

The nudged elastic band (NEB) method has been used to re-examine the oxidative addition step in the classic rhodium-catalyzed hydroacylation reaction. Numerous additional intermediates were found on a pathway that is lower in energy than that originally reported. This study illustrates the potential limitations of the traditional approach to locating transition states in which a chemical-intuition-guided linear or quadratic synchronous transit is used to estimate the high point of the reaction trajectory. Utilization of that approach constrains the search so that the actual transition state and other possible intermediates and transition states may be missed.