Chiral N-triflylphosphoramide-catalyzed asymmetric hydroamination of unactivated alkenes: a hetero-ene reaction mechanism

A highly enantioselective intramolecular hydroamination reaction catalyzed by chiralN-triflylphosphoramide (NTPA) that features an exceptionally broad substrate scope of isolated unactivated alkenes was recently reported by some of us. Herein we report a detailed density functional theory(DFT) study that unveil an uncommon hetero-ene reaction mechanism for this transformation. The reaction changes from a stepwise mechanism involving discrete tertiary carbocation formation to a concertedmechanism to avoid the generation of energetically unfavorable secondary carbocation species for distinctly substituted alkene substrates. The reactivity of this reaction is primarily affected by the substituentson the internal carbon of the alkene, with the carbocation-stabilizing ones promoting the reaction. Inaddition, the reaction is also influenced by the substituents on the terminal alkene carbons: those diminishing the innate alkene polarization of the starting alkenes retard the reaction by disfavoring the formation of related transition states featuring highly polarized alkene residues. The steric effect of all thesealkene substituents was found to be largely unimportant due to the unique arrangement of the heteroene reaction complex that keeps the reacting alkene away from the sterically congested core region ofthe catalyst pocket. The lower acidity of chiral phosphoric acids than that of chiral NTPAs renders the protonated precomplex along the hetero-ene reaction pathway greatly thermodynamically disfavored. Thisindirectly results in a greater relative distortion in the corresponding transition state, which in turn causesreaction retardation. Our results demonstrate the use of intramolecular pericyclic reactions as an alternative strategy for alkene activation by chiral Brønsted acid catalysis and provide insights into the furtherdevelopment of asymmetric hydrofunctionalization of unactivated alkenes.