Synthesis of Optically Active β,γ-Unsaturated α-Amino Acids and of α,β-Unsaturated γ-Amino Acids. S_N2- vs. S_N2’-Dichotomy of the Mitsunobu Amination of Allylic Alcohols

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_N2 inversion, whereas the γ-substitution corresponds to an (E)-anti attack of the nucleophilic with varying stereoselectivities.

chiral secondary allylic alcohols - Mitsunobu reaction - allylic transportation - S_N2 vs. S_N2’-substitution - anti-stereoselectivity in S_N2’-attack