Organolanthanide-Catalyzed Hydroamination. A Kinetic, Mechanistic, and Diastereoselectivity Study of the Cyclization of N-Unprotected Amino Olefins

Michel R. Gagné, Charlotte L. Stern, Tobin Jay Marks*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

513 Scopus citations


This contribution reports the efficient, regiospecific Cp′2LnR [Cp′ = η5-Me5C5; R = H, CH(TMS)2, η3-C3H5, N(TMS)2; Ln = La, Nd, Sm, Y, Lu]-catalyzed hydroamination/cyclization of the amino olefins H2NCHR1R2CH=CH2 to yield the corresponding heterocycles HNCH(R1)R2CHCH3, where R1, R2, Nt (turnover frequency, h−1), °C: H, (CH2)2, 140, 60 °C; H, CMe2CH2, 95, 25 °C; H, (CH2)3, 5, 60 °C; CH3, (CH2)2, 45, 25 °C; H, CH(Me)CH2, 38, 25 °C; and o-C6H4, CH2, 13, 80 °C. In addition, Me2Si(Me4C5)2NdCH(TMS)2 effects the cyclization of CH3HN(CH2)3CH=CH2 and H2NCH2CMe2(CH2)3CH=CH2 with Nt = 11 h−1 (25 °C) and 0.3 h−1 (60 °C), respectively. Reactions are zero-order in substrate over 3 or more half-lives, and for the cyclization of H2N(CH2)3CH=CH2 by catalyst precursor Cp′2LaCH(TMS)2, ΔH = 12.7 (1.4) kcal mol−1 and ΔS = −27 (5) eu. Kinetic isotope effects (kH/kD) of 2.7 (4) (60 °C), 5.2 (8) (25 °C), and 4.1 (8) (25 °C) are observed for the Cp′2LaCH(TMS)2-induced cyclizations of D2N(CH2)3CH=CH2, D2NCH(CH3)(CH2)2CH=CH2, and D2NCH2C(CH3)2CH2CH=CH2, respectively. Cyclization yields the corresponding DNCH(R1)R2CHCH2D isotopomers exclusively. Cyclization of H2NCH2C(CH3)2CH2CH=CH2 by catalyst precursor Cp′2LaCH(TMS)2 exhibits the solvent effect, ktoluene/kTHF = 5.3 (5). The complexes Cp′2LnNHR(H2NR) (Ln = La, R = CH3, CH2CH3; Ln = Nd, R = CH2CH3) and Cp′2LaNCH(CH3)CH2CR2CH2(HNCH(CH3)CH2CR2CH2) (R = H, CH3) were synthesized to model species in the catalytic cycle. Crystallographic data for Cp′2LaNHCH3(H2NCH3) at −120 °C were as follows: P21/n, Z = 4, a = 19.901 (4) Å, b = 11.695 (3) Å, c = 20.202 (3) Å, β = 97.95 (2)°, and R(F) = 0.049 for 3296 independent reflections with I > 2.58σ(I). Two independent molecules crystallize per unit cell with average La-NHCH3 and La←NH2CH3 bond distances of 2.31 (1) and 2.70 (1) Å, respectively. The two molecules differ slightly in relative orientations of the NCH3 groups. The amine-amido complexes undergo rapid intramolecular proton transfer between amine and amido ligands (ΔG ≈ 12.4 ± 0.5 kcal mol−1). Intermolecular exchange with free amine is rapid on the NMR time scale at −80 °C. The ordering of precatalyst activities, (Cp′2LaCH(TMS)2 > Cp′2SmCH(TMS)2 > Cp′2LuCH(TMS)2; Et2Si(C5H4)(Me4C5)LuCH(TMS)2 > Me2Si(Me4C5)2LuCH(TMS)2 > Cp′2LuCH(TMS)2) accords with known olefin insertion reactivities. Diastereoselection in H2NCH(CH3)(CH2)2CH=CH2 (5) cyclization depends on both lanthanide and ancillary ligation. Final 2,5-dimethylpyrrolidine trans:cis ratios in LnLnR-catalyzed reactions for Ln, Ln, trans:cis, °C are as follows: Cp′2, La, 3:2, 50 °C; Cp′2, La, 5:1, 25 °C; Cp′2, La, 8:1, 0 °C; Cp′2, Nd, 1:1.25, 25 °C; Cp′2, Sm, 1:1.25, 25 °C; Cp′2, Y, 8:1, 25 °C; Me2Si(Me4C5)2, Y, 3:1, 25 °C; Et2Si(H4C5)(Me4C5), Y, 18:1, 25 °C; Et2Si(H4C5)(Me4C5), Lu, 4:1, 25 °C. For the Cp′2LaCH(TMS)2-catalyzed case, the trans:cis ratio is also dependent on the extent of conversion and initial substrate:catalyst ratio. In contrast to 5, 5d2 exhibits low diastereoselectivity which is independent of conversion. In the presence of 3 equiv of n-propylamine, the Cp′2LaCH(TMS)2-catalyzed cyclization of 5 affords a >50:1 trans:cis product ratio. Mechanistic evidence suggests that olefin insertion into the Ln-N bond of the amine-amido complexes is turnover-limiting and is followed by a rapid protonolysis of the resulting Ln-C bond. The proposed catalytic mechanism invokes parallel manifolds, with one manifold populated at high amine concentrations exhibiting high diastereoselectivity in the cyclization of 5, and with the second, favored at low substrate concentrations, exhibiting lower diastereoselectivity. The catalyst at high amine concentrations is postulated to be a Ln(amido)(amine)2 complex.

Original languageEnglish (US)
Pages (from-to)275-294
Number of pages20
JournalJournal of the American Chemical Society
Issue number1
StatePublished - Jan 1 1992

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry


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