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 H2 as the H-source
and NH4OAc 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 NH4OAc, 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.