Chirality Transfer and Thiazolidine or Thiazine Formation in Reactions of L and D Enantiomers of β- or γ-Sulfhydryl Amino Acids with Imidazole Carboxaldehydes and Nickel(II)

The reaction of either the L or D enantiomer of H2N-C*H(R)CO2− (R = -CH2SH cysteine, C; -C(SH)(CH3)2, penicillamine, PN; or -CH2CH2SH, homocysteine, HC) with an imidazole-4-carboxaldehyde and nickel(II) acetate in methanol yields a single stereoisomer of a thiazolidine (from C or PN) or a thiazine (from HC) nickel complex. Five pairs of enantiomeric products were prepared and characterized by IR, ESI MS, EA, and single crystal structure determination. There is retention of chirality for the thiazolidine and thiazine complexes on ring position 4, Cα of the parent amino acid, and transfer of chirality to the newly generated stereogenic centers, ring positions 3 (the amino acid nitrogen atom, NAA) and 2 (the aldehyde carbon atom, Cald). For the thiazolidines, the new stereogenic centers, NAA, and Cald, have identical stereochemical assignments to one another and to the assignment of the alpha carbon atom, either all R from the L enantiomers of C and PN or all S from the D enantiomers of C and PN. For the thiazine products from HC, the newly generated stereogenic centers, ring positions 3 (NAA) and 2 (Cald), are identical to one another but opposite to that of the retained stereogenic center (ring position 4, the alpha carbon atom). Regardless of stereochemical assignment (R or S), the hydrogen atoms of Cα, NAA, and Cald, ring positions 4, 3, and 2, are always all cis to one another for the five pairs of enantiomers examined. This is a consequence of the fact that the thiazolidine and thiazine rings are fused to two other chelate rings of the complexes, which seems to explain the high stereospecificity observed in these systems.