Highly Enantioselective Zirconium-Catalyzed Cyclization of Aminoalkenes

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• 作者：Kuntal Manna ; William C. Everett ; George Schoendorff ; Arkady Ellern ; Theresa L. Windus ; Aaron D. Sadow
• 刊名：The Journal of the American Chemical Society
• 出版年：2013
• 出版时间：May 15, 2013
• 年：2013
• 卷：135
• 期：19
• 页码：7235-7250
• 全文大小：905K
• 年卷期：v.135,no.19(May 15, 2013)
• ISSN：1520-5126

文摘

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, 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鈥? equiv vs catalyst). Aminoalkenes are unchanged in the presence of a zirconium monoamido complex {PhB(C₅H₄)(Ox^4S-iPr,Me₂)₂}Zr(NMe₂)Cl or a cyclopentadienylmono(oxazolinyl)borato zirconium diamide {Ph₂B(C₅H₄)(Ox^4S-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鈥揷atalyst interaction preceding an irreversible step. Primary kinetic isotope effects from substrate conversion measurements (k鈥?sub>obs^(H)/k鈥?sub>obs^(D) = 3.3 卤 0.3) and from initial rate analysis (k₂^(H)/k₂^(D) = 2.3 卤 0.4) indicate that a N鈥揌 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 (螖S = 鈭?3(7) cal路mol^鈥? K^鈥?) and a remarkably low enthalpic barrier (螖H = 6.7(2) kcal路mol^鈥?). A six-centered, concerted transition state for C鈥揘 and C鈥揌 bond formation and N鈥揌 bond cleavage involving two amidoalkene ligands is proposed as most consistent with the current data.