Histidine and deuterium labelled histidine by asymmetric catalytic reduction with gaseous H2 or D2; the role of strong non-coordinating acids

An efficient and convenient route for the preparation of natural and unnatural histidine by asymmetric hydrogenation with rhodium–phosphine complexes is described. The reductions were performed in the presence of HBF4 to generate an essential imidazolyl cation. Stereoselective incorporation of D2 in the α,β-positions was obtained by catalytic deuteration in the presence of MeOD.

Figure optionsDownload as PowerPoint slide

(2R,3S)-Methyl 2-benzamido-3-(1H-imidazol-4-yl)(2,3-dideutero)propanoate[α]D25=+72.1 (c 0.5, HBF4 1.6 M in CH3OH)Absolute configuration: (2R,3S)

(2S,3R)-Methyl 2-benzamido-3-(1H-imidazol-4-yl)(2,3-dideutero)propanoate[α]D25=-70.7 (c 0.5, HBF4 1.6 M in CH3OH)Absolute configuration: (2S,3R)