Catalyzed stereo-selective hydrogenation of ynamides to give enamines: Ethanol as a hydrogen donor

The reaction mechanism of the Pd(PPh3)(4) -catalyzed stereo-selective hydrogenation of ynamide to enamine with ethanol as a hydrogenation agent was investigated using density functional theory (DFT). The computational study provides the unique multistep hydrogenation pathway with the reasonable energy barrier, and the low energy barriers through the proton shuttle process are well rationalized. The calculation predicts that the ynamide undergoes stepwise hydrogenation by Pd-activated ethanol species, Pd(PPh3)(4) acts as the precursor and the (EtOH)(2)-Pd-ynamide complex serves as active catalyst in the reaction. The calculation on the ynamide system indicates that there exist six competing reaction paths. For each path, the overall energy barrier is identified as the step corresponding to the oxidative addition of the O-H bond of the hydrogenating agent to palladium center of the catalytic-complex. Ethanol could play as a proton shuttle in the hydrogen transfer step and therefore dramatically decreases the energy barrier for this concerned transition state, which is further validated by turnover frequency (TOF) model. The high selectivity towards enamine is attributed to the post-transition-state dynamics in the second hydrogenation stage, which leads exclusively to the dissociation of the product. The predominant product with E-configuration is reproduced theoretically, which is consistent with the experimental observation. Reduced density gradient (RDG) analysis and atoms in molecules (AIM) of the transition states confirm the significant influence of ethanol on the mechanism and stereo selectivity. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

The study investigated the reaction mechanism of Pd-catalyzed ynamide hydrogenation with ethanol as a hydrogenation agent using DFT, revealing a multistep pathway with low energy barriers facilitated by ethanol as a proton shuttle. The high selectivity towards enamine was attributed to the post-transition-state dynamics in the second hydrogenation stage, with E-configuration as the predominant product, consistent with experimental observations.