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.