Theoretical Insights into the Mechanism of Ru(II)-Catalyzed Reductive Amination of Levulinic Acid to Chiral Pyrrolidinone

Although a Ru(II)-containing complex exhibits a good catalytic performance in the asymmetric reductive amination of levulinic acid (LA) to chiral 5-methyl-2-pyrrolidone (MPD), the underlying reaction mechanism remains unclear. For the asymmetric reductive amination of LA to MPD catalyzed by [LRu(PL)Cl]Cl (L= (R)-2,2′-bis(diphenylphosphanyl)-1,1′-binaphthalene, PL = p -cymol) with H 2 as the H-source and NH 4 OAc as the N -source in a trifluoroethanol (TFE) solution, the catalytic mechanism has been studied at the M06/def2-TZVP, 6–311++G (d,p) theoretical level. Upon dissociation in the TFE solution with NH 4 OAc, the [LRu(PL)Cl]Cl compound can form a stable complex LRu(OAc) 2 as the initial catalytically active species. The conversion of LA to MPD catalyzed by LRu(OAc) 2 is kinetically predominant through the reductive amination of the ketonic carbonyl (–C═O) group of LA. The rate-determining step is associated with C═N bond formation for ring-closure, and the chirality-controlling step is concerned with C═H bond formation for hydrogenation. In protic solvents, the higher catalytic activity of LRu(OAc) 2 is associated with a lower solvent dielectric constant. The above theoretical results are in good agreement with the experimental findings reported. The current research should provide some theoretical clues for designing novel catalysts for the asymmetric reductive amination of ketone carbonyl-containing compounds to a chiral product.