Stereoselective Synthesis of Chiral Pyrrolidine Derivatives of (+)-α-Pinene Containing a β-Amino Acid Moiety

We report the synthesis of several enantiopure pyrrolidine derivatives containing a beta-amino acid moiety. These novel chiral compounds were prepared through stereospecific chlorosulfonyl isocyanate (CSI) addition to the readily available, natural terpene (+)-alpha-pinene. Coupling of N-Boc-protected beta-amino acid derivatives with various bulky amines and amino acids using the mixed anhydride activation method, followed by N-deprotection, afforded the corresponding chiral amino amides in good yields. Despite the severe steric hindrance anticipated in a-pinene-based heterocycles, efficient coupling of the amino amides and an amino ester with the acyl chloride of N-Cbz-protected (S)-proline provided the corresponding pyrrolidinic pinene derivatives in good yields. Moreover, a convenient synthesis of N-Cbz-and N-Boc-monoprotected (S)-prolinamine is reported.