Highly Enantioselective Zirconium-Catalyzed Cyclization of Aminoalkenes

Aminoalkenes are catalytically cyclized in the presence of cyclopenta­dienyl­bis­(oxazolinyl)­borato group 4 complexes {PhB­(C₅H₄)­(Ox^R)₂}­M­(NMe₂)₂ (M = Ti, Zr, Hf; Ox^R = 4,4-dimethyl-2-oxazoline, 4<i>S</i>-isopropyl-5,5-dimethyl-2-oxazoline, 4<i>S</i>-<i>tert</i>-butyl-2-oxazoline) at room temperature and below, affording five-, six-, and seven-membered N-heterocyclic amines with enantiomeric excesses of >90% in many cases and up to 99%. Mechanistic investigations of this highly selective system employed synthetic tests, kinetics, and stereochemistry. Secondary aminopentene cyclizations require a primary amine (1–2 equiv vs catalyst). Aminoalkenes are unchanged in the presence of a zirconium monoamido complex {PhB­(C₅H₄)­(Ox^{4<i>S</i>‑<i>i</i>Pr,Me₂})₂}­Zr­(NMe₂)Cl or a cyclopenta­dienyl­mono­(oxazolinyl)­borato zirconium diamide {Ph₂B­(C₅H₄)­(Ox^{4<i>S</i>‑<i>i</i>Pr,Me₂})}­Zr­(NMe₂)₂. Plots of initial rate versus [substrate] show a rate dependence that evolves from first-order at low concentration to zero-order at high concentration, and this is consistent with a reversible substrate–catalyst interaction preceding an irreversible step. Primary kinetic isotope effects from substrate conversion measurements (<i>k</i>′_obs^(H)/<i>k</i>′_obs^(D) = 3.3 ± 0.3) and from initial rate analysis (<i>k</i>₂^(H)/<i>k</i>₂^(D) = 2.3 ± 0.4) indicate that a N–H bond is broken in the turnover-limiting and irreversible step of the catalytic cycle. Asymmetric hydroamination/cyclization of <i>N</i>-deutero-aminoalkenes provides products with higher optical purities than obtained with <i>N</i>-proteo-aminoalkenes. Transition state theory, applied to the rate constant <i>k</i>₂ that characterizes the irreversible step, provides activation parameters consistent with a highly organized transition state (Δ<i>S</i>^⧧ = −43(7) cal·mol^–1 K^–1) and a remarkably low enthalpic barrier (Δ<i>H</i>^⧧ = 6.7(2) kcal·mol^–1). A six-centered, concerted transition state for C–N and C–H bond formation and N–H bond cleavage involving two amidoalkene ligands is proposed as most consistent with the current data