Efficient Access to Chiral 2-Oxazolidinones via Ni-Catalyzed Asymmetric Hydrogenation: Scope Study, Mechanistic Explanation, and Origin of Enantioselectivity

Cheap transition metal Ni-catalyzed asymmetric hydrogenation of 2-oxazolones was successfully developed, which provided an efficient synthetic strategy to prepare various chiral 2-oxazolidinones with 95%–99% yields and 97%−>99% ee. The gram-scale hydrogenation could be proceeded well with >99% ee in the presence of low catalyst loading (up to 3350 TON). This Ni-catalyzed hydrogenation protocol demonstrated great synthetic utility, and the chiral 2-oxazolidinone product was easily converted to a variety of other important molecules in good yields and without loss of ee values, such as chiral dihydrothiophene-2(3H)-thione, amino alcohol, oxazoline ligand, and allenamide. Moreover, a series of deuterium labeling experiments, control experiments, and DFT calculations were conducted to illustrate a reasonable catalytic mechanism for this Ni-catalyzed asymmetric hydrogenation, which involved a tautomerization between the enamine and its isomer imine and then went through asymmetric 1,2-addition of Ni(II)-H to the preferred imine.