A cheap metal for a challenging task: nickel-catalyzed highly diastereo- and enantioselective hydrogenation of tetrasubstituted fluorinated enamides

Abstract

Nickel-catalyzed asymmetric hydrogenation of challenging tetrasubstituted fluorinated enamides has been achieved, affording chiral α-fluoro-β-amino esters in high yields with excellent diastereo- and enantioselectivities (up to 98% yield, >99 : 1 dr, up to >99% ee). Deuterium-labeling experiments and control experiments were conducted to probe the mechanism, and the results indicated that the acidity of the solvent plays a critical role in the control of diastereoselectivity by trapping the adduct of nickel hydride to C[double bond, length as m-dash]C bonds <i>via</i> protonolysis, giving the hydrogenation product with stereospecific <i>syn</i>-selectivity. This protocol provides efficient access to chiral α-fluoro-β-amino esters which have important potential applications in organic synthesis and medicinal chemistry.