Conformation of Protected Amino Acids. V. Application of Lanthanide-Shift Reagents for Conformational Studies of tert-Butoxycarbonyl α-Amino Acid Esters: Equilibrium Changes and Kinetics of the Isomerization

¹H and ¹³C NMR studies show that in the E,Z-conformational equilibrium of Boc α-amino acid esters (Gly, Ala, Phe) the Z rotamer dominates. The addition of Eu(fod)₃ increases the amount of the E rotamer by preferred complexation. This directly observable change in equilibrium is caused by the increased size of the complexed urethane carbonyl group accompanied by the higher steric hindrance in the Z rotamer. Complete line shape analysis of Boc-Gly-OCH₃-d₃ at four different concentrations of Eu(fod)₃-d₂₇ proves that the observed barrier of rotation (ΔG^╪_Z→E= 66.8 kJ/mol, ΔH^╪_Z→E = 65.7 kJ/mol, ΔS^╪_Z→E= 4.7 J/deg mol) reflects the barrier of the uncomplexed substrate. The change in the isomerization barriers E → Z with increasing LSR concentration parallels the ground state stabilization of the E rotamer.