The mechanism of PNN-Mn-catalyzed asymmetric hydrogenation of 3H-indole.

• Clarifying the role of coordination structure of the active site for the asymmetric hydrogenation. • Elucidating the influence of excess base in reaction for metal ligand cooperation. • Revealing the importance of steric effect between reactant and catalyst in the asymmetric hydrogenation. The asymmetric hydrogenation of 3H-indole is highly important for the synthesis of chiral indole as potential biologically active products and drugs. To better understand the mechanism and the origin of enantioselectivity for PNN-Mn-catalyzed asymmetric hydrogenation of 3H-indole, density functional theory studies were performed to study the influence of the coordination geometry and the deprotonation by additive base on the reaction. Our results revealed that the coordination structure of the active species adopts the fac- geometry rather than the mer- geometry. The excess additive base is crucial for the deprotonation of the pre-catalyst. The most plausible active species should be doubly deprotonated at the amine site and the imidazole site. The comparison of detailed potential energy surfaces for possible active species at different deprotonation situations suggests that the hydride transfer from the metal hydride to the reactant is the key step for the asymmetric reaction, in which the R -configuration transition state is found to be preferred over the S -configuration one(yielding a theoretical ee value of 98.5 %), in good agreement with the experimental results(97 % ee). Noncovalent interaction analysis of the key transition states found that the steric effect during hydride transfer plays an important role in enantioselectivity. [Display omitted] [ABSTRACT FROM AUTHOR]