ENANTIOSELECTIVE SYNTHESIS OF HOMOALLYLIC AMINES BY ADDITION OF ALLYLMETAL REAGENTS TO IMINES DERIVED FROM (S)-VALINE ESTERS

Grignard and Barbier procedures have been applied to the addition of allylmetal (Zn, Cu, Pb, Bi, Al, In) species to imines derived from (S)-valine esters, principally the methyl ester. The Zn-mediated, CeCl3- or SnCl2-catalyzed ''Barbier'' reactions of the imines with allyl bromide in THF in Ar atmosphere at room temperature proved particularly convenient, efficient and selective, providing the secondary homoallylic amines with excellent to perfect diastereoselectivity. The si face of the imine was attacked preferentially in every case. The addition of allylzinc bromide to aromatic imines was affected by reversibility, which caused the lowering of the diastereoisomeric ratio with increasing the reaction time. However, the retroallylation reaction could be avoided by performing the reaction in the presence of trace amounts of water, or by using CeCl3.7H(2)O as the catalyst, although at the expense of the reaction rate. The bimetal redox systems Al-PbBr2, -SnCl2, -TiCl4, and -BiCl3 were applied to the allylation of the imines derived from methyl valinate, but satisfactory results were achieved only with Al-BiCl3 and -TiCl4 systems. However, the use of the Al(Hg) and Al-PbBr2 system afforded almost perfect chemo- and diastereoselectivity on the benzaldehyde imine derived from tert-butyl (S)-valinate. The synthesis of (S)-1-phenyl-3-butenamine from the corresponding secondary homoallylic amine was accomplished by a two-step sequence, consisting of the controlled reduction of the methyl ester with LiAlH4 and subsequent oxidative cleavage with H5IO6-MeNH(2).