Histidine and deuterium-labelled histidine by asymmetric catalytic reduction and assignment of the absolute stereochemistry by neutron diffraction

We describe an efficient and convenient route for the preparation of enantiomerically pure d-labelled histidine by asymmetric hydrogenation with a Rh–diphosphine complex in the presence of strong non-coordinating acids. A single-crystal neutron diffraction study of the selectively dideuterated N-benzoyl-histidine methyl ester, tetrafluoroborate salt determined the absolute stereochemistry. This allowed us to clarify the role of H+ in the whole reduction process.

Figure optionsDownload as PowerPoint slide

(2R,3S)-Methyl 2-benzamido-3-(1H-imidazol-4-yl)(2,3-dideutero)propanoateC14H15N302[α]D25=+72.1 (c 0.5 in HBF4 1.6 M in CH3OH)Absolute configuration: (2R,3S)