Highly Enantioselective Zirconium-Catalyzed Cyclization of Aminoalkenes

Aminoalkenes
are catalytically cyclized in the presence of cyclopenta­dienyl­bis­(oxazolinyl)­borato
group 4 complexes {PhB­(C5H4)­(OxR)2}­M­(NMe2)2 (M = Ti, Zr, Hf; OxR = 4,4-dimethyl-2-oxazoline, 4S-isopropyl-5,5-dimethyl-2-oxazoline,
4S-tert-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)­(Ox4S‑iPr,Me2)2}­Zr­(NMe2)Cl or a cyclopenta­dienyl­mono­(oxazolinyl)­borato
zirconium diamide {Ph2B­(C5H4)­(Ox4S‑iPr,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
(k′obs(H)/k′obs(D) = 3.3 ± 0.3) and from initial
rate analysis (k2(H)/k2(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 N-deutero-aminoalkenes provides products with
higher optical purities than obtained with N-proteo-aminoalkenes.
Transition state theory, applied to the rate constant k2 that characterizes the irreversible step, provides activation
parameters consistent with a highly organized transition state (ΔS⧧ = −43(7) cal·mol–1 K–1) and a remarkably low enthalpic barrier (ΔH⧧ = 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.