Enantiomer selection in the addition reaction of optically active 3-methyl-5-substituted hydantoins to N-[(S)-α-methylbenzyl]glycine N-Carboxyanhydride: Model Reaction for the Stereoselective Polymerization of α-amino acid N-carboxyanhydride

In order to investigate the contribution from the chiral penultimate unit to the enantiomer selection in the activated N-carboxyanhydride (NCA) polymerizations, the addition reaction to N-(S)-methylbenzyl]glycine NCA of various α-amino acid hydantoins activated by the tertiary amines was investigated in different solvents. The reactions of activated Ala, Val, and Phe hydantoins were stereoselective and suggested the participation of the penultimate unit in the enantiomer selection of the activated NCA type of polymerization. The degree of enantiomer selection was not well correlated with the structure of hydantoins. Taking into account the dipole repulsion and the orbital overlapping between the reaction species, the transition-state model was proposed, which gave a good explanation of the selectivity for (R)-hydantoin in PhNO₂ and CH₃CN and the selectivity for (S)-hydantoin in AcNMe₂ and HCONMe₂. In these two types of solvents the orientation of the methylbenzyl group with respect to the NCA ring is so different that the direction of the approach of the activated hydantoin to the NCA is different. This difference leads to the inversion of enantiomer selection in amide solvents and in others. Cationic species derived from tertiary amines and the chiral amide compound were found to affect the enantiomer selection in the model reaction. The implications of these findings with regard to enantiomer selection in the activated NCA type of polymerization are discussed.