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.