Synthesis of optically active β,γ-unsaturated α-amino acids of α,β-unsaturated γ-amino acids. S(N)2- vs. S(N)2'-dichotomy of the Mitsunobu amination of allylic alcohols

Article abstract of DOI:10.1055/s-1995-3847

Novel and efficient syntheses (6-9 steps, overall yields 10-30%) are described for optically pure β,γ-unsaturated α-amino acids and α,β-unsaturated γ-amino acids, starting from (R)-isopropylidene glyceraldehyde and ethyl (S)-lactate, respectively. The key step is the Mitsunobu reaction of chiral secondary allylic alcohols with phthalimide as the nucleophile, where α,γ allylic transpositions are observed for the first time. The structure-α,γ-ratio-relationship is studied and also the stereochemistry of the allylic transposition. The α-substitution proceeds via clean S(N)2 inversion, whereas the γ-substitution corresponds to an (E)-anti attack of the nucleophilic with varying stereoselectivities.