Solvent effect on the stereoselective addition reaction of optically active amines to N-methylphenylalanine N-carboxyanhydride

The effect of solvent on stereoselectivity in the nucleophilic addition reaction of various optically active amines to N-methylphenylalanine N-carboxyanhydride has been investigated. In m-dimethoxybenzene as solvent, (S)-valine, (S)-leucine, and (S)-phenylalanine ethyl esters reacted preferentially with (R)-N-methylphenylalanine N-carboxyanhydride, but the stereoselectivity decreased considerably in nitrobenzene and dimethylacetamide as solvents. In the latter solvents, the dipolar interactions between an amine and an N-carboxyanhydride and the orientation of the substituent of N-carboxyanhydride were seriously affected, hence the stereoselectivity decreased. As a consequence, the enantiomer selection by the terminal amine of a growing chain in the nucleophilic addition-type polymerization of α-amino acid N-carboxyanhydride can be controlled by the choice of solvent. (S)-Proline ethyl ester and (S)-α-phenylethylamine reacted preferentially with (S)-N-methylphenylalanine N-carboxyanhydride in m-dimethoxybenzene, and this type of selectivity did not change in nitrobenzene. But in dimethylacetamide the stereoselectivity decreased. In the transition state of the reaction of these amines and N-methylphenylalanine N-carboxyanhydride dipolar interactions are operating, which should be destroyed by dimethylacetamide but may not be affected by nitrobenzene.