Mechanism of Catalytic Cyclohydroamination by Zirconium Salicyloxazoline Complexes

Abstract

The mechanism of hydroamination/cyclization of primary aminoalkenes by catalysts based on Cp*LZr(NMe(2))(2) (L = κ(2)-salicyloxazoline) is investigated in a range of kinetic, stoichiometric, and structural studies. The rate law is found to be d[substrate]/dt = k[catalyst](1)[substrate](0) for all catalysts and aminoalkenes studied. The overall rate is similar for formation of five- and six-membered rings, and a substantial KIE (k(H)/k(D)) is observed, indicating the involvement of N-H bond-breaking in a rate-determining step (RDS) which is not ring-closure. Remarkably, the reaction proceeds at the same rate in THF as it does in toluene, but added non-cyclizable amine slows the reaction, indicating that while the metal is not acting as a Lewis acid in the RDS, the activated substrate is involved. Also in contrast to other catalysts, increasing steric bulk improves the rate, and the origins of this are investigated by X-ray crystallography. Thermodynamic parameters extracted from eight independent kinetic studies indicate moderate ordering (ΔS(double dagger) = -13 to -23 cal/K·mol) and substantial overall bond disruption (ΔH(double dagger) = 17 to 21 kcal/mol) in the rate-determining transition state. Secondary amines are unreactive, as is a catalyst with a single aminolyzable site, thus excluding an amido mechanism. A catalytic cycle involving rate-determining formation of a reactive imido species is proposed. Stoichiometric steps in the process are shown to be feasible and have appropriate rates by synthetic and in situ NMR spectroscopic studies. The fate of the catalyst in the absence of excess amine (at the end of the catalytic reaction) is conversion to a metallacyclic species arising from CH activation of a peripheral substituent.

Migratory Insertion of Alkenes into Metal–Oxygen and Metal–Nitrogen Bonds

“…An alternate explanation for the primary kinetic isotope effect and zero-order dependence on substrate concentration is reaction by a mechanism involving turnover-limiting formation of a metal imido intermediate. [73,74] Additional studies are clearly needed to delineate the relationships between the experimental data and mechanisms of hydroamination catalyzed by alkaline earth, group IV, and lanthanide complexes.…”

Transition‐Metal‐Catalyzed Hydroamination Reactions

“…Indeed, early computational work on a cyclopentadienyl system suggested that while the [2+2] cycloaddition step is energetically feasible, the subsequent protonolysis step for catalyst turnover is turnover-limiting [40,59]. More recently, Scott and coworkers [60] showed experimentally that proton transfer in the release of product and generation of the requisite zirconium imido complex can be turnover-limiting (Scheme 15.10). Previously reported bis(amidate)-and tethered-amidate-supported zirconium complexes can be used for alkene hydroamination catalysis, and all substrate scope and mechanistic investigations of these systems are consistent with the [2+2] cycloaddition mechanistic profile [61,62].…”

Migratorische Insertion von Alkenen in Metall‐Sauerstoff‐ und Metall‐Stickstoff‐Bindungen

“…Anschließend schlugen Schafer und Mitarbeiter einen ähnlichen Übergangszustand für die Hydroaminierung primärer und sekundärer Aminoalkene vor, die durch Zirconium-Komplexe mit anhängendem Bis(ureat) katalysiert wurden. [73,74] Weitere Studien sind eindeutig erforderlich, um die Beziehungen zwischen den Versuchsdaten und den Mechanismen der Hydroaminierungen, die durch Erdalkali-, Gruppe-IV-und Lanthanoid-Komplexe katalysiert werden, zu beschreiben. [53,[58][59][60] Die Reaktionsordnung bezüglich dem Substrat in Verbindung mit Informationen über den Ruhezustand sowie die KIE-Werte deuten auf Parallelen zwischen diesen Systemen hin.…”

“…Eine alternative Erklärung für den primären kinetischen Isotopeneffekt und die Abhängigkeit erster Ordnung von der Substratkonzentration ist eine Reaktion, deren Mechanismus die Bildung eines Metall-Imido-Intermediats als umsatzbestimmenden Schritt enthält. [73,74] Weitere Studien sind eindeutig erforderlich, um die Beziehungen zwischen den Versuchsdaten und den Mechanismen der Hydroaminierungen, die durch Erdalkali-, Gruppe-IV-und Lanthanoid-Komplexe katalysiert werden, zu beschreiben.…”