DFT study of the origin of enantioselectivity of Ni-catalyzed asymmetric hydrogenation of cyclic sulfamidate imine to chiral cyclic sulfamidates

In this study, we elucidate the origin of enantioselectivity in Ni-catalyzed asymmetric hydrogenation of cyclic sulfamidate imines to chiral cyclic sulfamidates using the chiral (S,S)-Ph-BPE ligand, based on DFT calculations (ωB97XD/6–311 + G(d,p), SMD(TFE) // ωB97XD/6-31G(d,p), SMD(TFE), SDD for Ni). The DFT results reveal that the addition of [Ni]-H to the CN bond of the cyclic sulfamidate imine is the enantioselectivity-determining step. The high enantioselectivity of the desired S-product is attributed to favorable CH-π attractive interactions in the S-pathway, whereas the R-pathway, characterized by lone-pair-π repulsion, is energetically less favorable, leading to lower enantioselectivity. Furthermore, the enantiomeric excess (ee), calculated using the Energetic Span Model and Transition State Theory, exceeds 99 % in favor of the S-enantiomer. Despite this, the DFT-predicted %ee values qualitatively align with the experimentally observed enantioselectivity of ee >94 %. Additionally, modifying the R substituent of the substrate from phenyl to methyl resulted in a significant decrease in ΔΔG^‡, from 3.9 kcal/mol for the phenyl group to 2.2 kcal/mol for the methyl group. This trend aligns with experimental results. These findings lay the groundwork for the development of advanced chiral catalysts for the enantioselective hydrogenation of cyclic sulfamidate imine substrates.