Ta-Catalyzed Hydroaminoalkylation of Alkenes: Insights into Ligand-Modified Reactivity Using DFT

Density functional theory (DFT) calculations were performed to probe the mechanism of tantalum-catalyzed hydroaminoalkylation, a reaction that affords Csp3–Csp3 bond formation via α-alkylation of a secondary amine with an alkene. Electronic effects in catalyst design were probed to reveal key features in the energy profile of the proposed mechanism, corroborating experimental trends in which electrophilic metal centers demonstrate enhanced reactivity. Modeling of the energy profile with an N,O-chelating amidate Ta catalyst (I) revealed profound differences in relative energetics, rationalizing improvements that have been observed using sterically and electronically varied ligands. N,O-Chelating ligands electronically promote preferential reactivity in the equatorial plane. The turnover-limiting step can be completely changed depending upon the ligand; for sterically bulky monoamidate complexes, the protonolysis of an intermediate metallacycle is the turnover-limiting step rather than C–H activation, as has been found for systems lacking steric bulk. Unproductive off-cycle pathways were also modeled to compare with experimental studies. These insights contribute to a theoretical understanding of key features in ligand design for developing improved catalysts for hydroaminoalkylation.