Comprehensive Experimental and Theoretical Studies of Configurationally Labile Epimeric Diamine Complexes of α-Lithiated Benzyl Carbamates

Abstract

Different primary benzyl-type carbamates were deprotonated by sec-butyllithium in the presence of a tert-leucinol-derived bis(oxazoline) ligand. The resulting configurationally labile epimeric complexes equilibrated and one diastereomer was strongly favored in the equilibria. After dynamic thermodynamic resolution, the complexes could be trapped with different classes of electrophiles to yield highly enantioenriched secondary benzyl carb­amates. The stereochemical course of the substitution reactions was elucidated. High-level quantum chemical investigations were performed and allowed a prediction of both the favored complex and the enantiomeric excess that could be expected within the reactions.

Key words

asymmetric synthesis - carbanions - lithium - bis(oxazoline) ligands - quantum chemical calculations

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26

Within a dynamic thermodynamic resolution: ΔΔG = RT˙ln(e.r.), ΔΔE ≈ ΔΔH(0 K) ≈ ΔΔG = ΔΔH - TΔΔS.

32

X-ray crystal structure analysis for (R)-20f: formula C₂₁H₂₄BrNO₃, M = 418.32, colorless crystals 0.30 × 0.30 × 0.15 mm, a = 5.774(1), b = 17.816(1), c = 19.291(1) Å, V = 1984.5(4) Å^³, ρ_calcd = 1.400 g cm^-³, µ = 29.81 cm^-¹, empirical absorption correction (0.468 ≤ T ≤ 0.663), Z = 4, orthorhombic, space group P2₁2₁2₁ (No. 19), λ = 1.54178 Å, T = 223 K, ω and ϕ scans, 9441 reflections collected (±h, ±k, ±l), [(sinθ)/λ] = 0.60 Å^-¹, 3384 independent (R _int = 0.034) and 3338 observed reflections [I ≤ 2 σ(I)], 239 refined parameters, R = 0.028, R _w ^² = 0.074, Flack parameter -0.021(15), max. residual electron density 0.28 (-0.24) e Å^-³, hydrogen atoms calculated and refined as riding atoms, CCDC 684786.

36

All the bis(oxazoline) 9d containing complexes calculated show values for this sum of angles between 314˚ [(R _C)-33˙9d] and 316˚ [(R _C)-32˙9d] for the favored R _C-configured epimers and values around 312˚ to 313˚ for the unfavored S _C-configured epimers.

37

X-ray crystal structure analysis for (S,S)-29: formula C₂₁H₂₉NO₂Si, M = 355.54, colorless crystals 0.25 × 0.06 × 0.05 mm, a = 22.666(1), b = 7.897(1), c = 12.669(1) Å, β = 108.45(1)˚, V = 2151.1(3) Å^³, ρ_calcd = 1.0981 g cm^-³, µ = 10.52 cm^-¹, empirical absorption correction (0.779 ≤ T ≤ 0.949), Z = 4, monoclinic, space group C2 (No. 5), λ = 1.54178 Å, T = 223 K, ω and ϕ scans, 5904 reflections collected (±h, ±k, ±l), [(sinθ)/λ] = 0.59 Å^-¹, 2448 independent (R _int = 0.048) and 1962 observed reflections [I ≤ 2 σ(I)], 254 refined parameters, R = 0.052, R _w ^² = 0.122, Flack parameter 0.02 (6), max. residual electron density 0.17 (-0.23) e Å^-³, hydrogen atoms calculated and refined as riding atoms, CCDC 684785.

40

Tables containing the atom coordinates of the different complexes can be obtained from the author upon request.

48

SCHAKAL: Keller, E. University of Freiburg, Germany, 1997

49

These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via http://www.ccdc.cam.ac.uk/data request/cif.