SYNTHESIS OF OPTICALLY-ACTIVE BETA,GAMMA-UNSATURATED ALPHA-AMINO-ACIDS AND OF ALPHA,BETA-UNSATURATED GAMMA-AMINO ACIDS - S(N)2-DICHOTOMY VS S(N)2'-DICHOTOMY OF THE MITSUNOBU AMINATION OF ALLYLIC ALCOHOLS

Novel and efficient syntheses (6-9 steps, overall yields 10-30 %) are described for optically pure beta,gamma-unsaturated alpha-amino acids and alpha,beta-unsaturated gamma-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 alpha,gamma allylic transpositions are observed for the first time. The structure-alpha,gamma-ratio-relationship is studied and also the stereochemistry of the allylic transposition. The alpha-substitution proceeds via clean S(N)2 inversion, whereas the gamma-substitution corresponds to an (E)-anti attack of the nucleophilic with varying stereoselectivities.