Organolanthanide-catalyzed hydroamination. A kinetic, mechanistic, and diastereoselectivity study of the cyclization of N-unprotected amino olefins

Article abstract of DOI:10.1021/ja00027a036

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, N_t (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 N_t = 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 HvN(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 (k_H/k_D) 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(C-H₃)(CH₂)₂CH=CH₂, and D₂NCH₂C(CH₃)₂CH ₂CH=CH₂, respectively. Cyclization yields the corresponding DNCH-(R¹)R²CHCH₂D isotopomers exclusively. Cyclization of H₂NCH₂C(CH₃)₂CH ₂CH=CH₂ by catalyst precursor Cp'₂LaCH(TMS)₂ exhibits the solvent effect, k_toluene/k_THF = 5.3 (5). The complexes Cp'₂LnNHR(H₂NR) (Ln = La, R = CH₃, CH₂CH₃; Ln = Nd, R = CH₂CH₃) and Cp'₂LaNCH(CH₃)CH₂CR₂CH ₂(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, Z = 4, a = 19.901 (4) A?, b = 11.695 (3) A?, c = 20.202 (3) A, 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) A?, respectively. The two molecules differ slightly in relative orientations of the NCH₂ groups. The amine-amido complexes undergo rapid intramolecular proton transfer between amine and amido ligands (Δ? ≈ 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'₂mCH(TMS)₂ > Cp'₂LuCH(TMS)₂; Et₂Si(C₅H₄)-(Me₄C ₅)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 transtcis ratios in L_nLnR-catalyzed reactions for L_n, 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.