Temperature-Scanning Reaction Protocol Offers Insights into Activation Parameters in the Buchwald–Hartwig Pd-Catalyzed Amination of Aryl Halides

A temperature-scanning reaction (TSR) protocol allows deconvolution of the driving forces of concentration and temperature in a
single experiment, demonstrated here for the Buchwald −Hartwig amination reaction using different amine substrates that exhibit different ratedetermining steps. An Eyring analysis reveals that the observed reactivity differences between 1-hexylamine and benzophenone hydrazone are related primarily to the different contributions of activation entropy in the two cases. This TSR protocol combined with other in situ kinetic methodologies including reaction progress kinetic analysis and variable time normalization analysis provides a rapid and comprehensive mechanistic picture of complex multistep catalytic reactions.