GENERAL-METHOD FOR THE SYNTHESIS OF ENANTIOMERICALLY PURE BETA-HYDROXY-ALPHA-AMINO ACIDS, CONTAINING FLUORINE-ATOMS IN THE SIDE-CHAINS - CASE OF STEREOCHEMICAL DISTINCTION BETWEEN METHYL AND TRIFLUOROMETHYL GROUPS - X-RAY CRYSTAL AND MOLECULAR-STRUCTURE OF THE NICKEL(II) COMPLEXOF (2S,3S)-2-(TRIFLUOROMETHYL)THREONINE

The chiral Ni(II) complex 1 of a Schiff's base derived from (S)-o-[N-( N-benzylprolyl)amino]benzophenone (BPB) and glycine was treated with f luoro-substituted aldehydes (aliphatic and aromatic)in MeOH or CHCl3. The addition proceeds with high diastereoselectivity to give, if catal ysed by MeONa in MeOH, the corresponding complexes of syn-(2R)-3-fluor ophenylserines (84-100% d.e.) and syn-(2S)-fluoroalkylserines (90% d.e .), and, if catalysed by NEt3 or DABCO (MeOH or CHCl3), the correspond ing complexes of syn-(2S)-, and anti-(2S)-3-fluorophenylserines and fl uoroalkylserines. The second-order asymmetric transformation may be su ccessfully employed to obtain diastereoisomerically pure complexes of anti-(2R)-3-fluorophenylserines. Condensation of trifluoroacetone with complex 1, catalysed by MeONa, gave predominantly (at least >95% d.e. ) the diastereoisomeric complex, containing (2S,3S)-beta-(trifluoromet hyl)threonine, as shown by an X-ray diffraction structural study. Dias tereoisomerically and enantiomerically pure fluorine-containing 3-phen yl- and 3-alkyl-serines were obtained from the corresponding diastereo isomerically pure complexes, separated by chromatography or crystalliz ation. The initial chiral auxiliary BPB was recovered (80-98%). The in fluence of the reaction's conditions and the nature of the correspondi ng fluoro-substituted aldehydes on the diastereoselectivity of the rea ctions is discussed.