Theoretical Modeling of the Interaction Chiral Modifier/Substrate as a Key Step in the Enantioselective Hydrogenation of α-ketoesters and Vicinal Diketones
Jose F. Ruggera, Ayelen Gazquez, Reinaldo Pis Diez and Monica L. Casella
Affiliation: Centro de Investigación y Desarrollo en Ciencias Aplicadas “Dr. Jorge Ronco” (CINDECA), Facultad de Ciencias Exactas, Universidad Nacional de La Plata - CCT La Plata - CONICET, 47 N°257, 1900 La Plata, Argentina.
This paper deals with the computational modeling of the chiral modifier/substrate interaction for chiral modifiers
studied in our laboratory, different from those conventionally used in enantioselective hydrogenation reactions. (S)-
(+)-1-aminoindane and (R)-(-)-1-aminoindane were chosen as chiral modifiers and the selected substrates were methyl pyruvate,
ethyl pyruvate and 1-ethyl-4,4-dimethyl-pyrrolidinae-2,3,5-trione.
The geometry of each of the chiral modifier/substrate complexes was optimized using DFT calculations and a BLYP functional.
The theoretical enantiomeric excess was calculated from the energy of each of the proposed complexes. The calculations
were carried out considering different reaction solvents through the use of COSMO program.
It was found that this simple model allows predicting the experimental values of both the sense of enantiodifferentiation
and the enantiomeric excess with a good approximation. It was also able to predict the inversion of configuration when
using the (S)-(+)-1-aminoindane as chiral modifier in polar solvents such as acetic acid and 2-propanol.
Keywords: Theoretical modeling, Enantioselectivity, DFT, Hydrogenation, Chiral modifiers, Aminoindane.
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