Gold(I)-catalyzed alkene hydroamination: revelations from kinetic benchmarking

Kinetic and reactivity studies on the intramolecular hydroamination of 1-allyl-1,3-diphenylurea and related analogues, as well as protected variants of 2-(allyloxy)aniline using both gold(I) and acid catalysts revealed gold catalyst resting states and deactivation pathways. The structure of the phosphine ligand and counterion on gold impacted the extent to which alkylgold intermediates could be detected, and, at higher temperatures, the rate of reaction with 1,2-dichloroethane (DCE) solvent to generate inactive LAuCl and Brønsted acid by-product. Comparisons to the reactivity of urea, carbamate, thiourea, and thiocarbamate showed that failure of gold to enable catalytic hydroamination does not correlate with failure to activate alkenes toward nucleophilic addition to form alkylgold intermediates. Furthermore, the presence of electron-withdrawing groups on the phosphine ligand can lead to increases in reactivity, despite greater amounts of deactivated complex. Acid catalysts are shown to react markedly different from gold catalysts, and in one case a cooperative effect was identified whereby a gold/acid mixture led to a faster rate by perturbing alkylgold intermediate concentration. The impact of counterion was not consistent across all substrates, suggesting a complex role.