MM3 force field prediction of the enantioselective preference in the asymmetric synthesis of a chiral 2-cyclohexen-1-ol using a chiral lithium amide reagent

Autor: Kazuhisa Sakakibara, Jenn-Huei Lii, Norman L. Allinger, Hayato Hoshino, Masatoshi Asami
Rok vydání: 2008
Předmět:
Zdroj: Tetrahedron. 64:575-581
ISSN: 0040-4020
DOI: 10.1016/j.tet.2007.10.110
Popis: Enantioselective preference in the asymmetric synthesis where cyclohexene oxide is transformed enantioselectively to chiral (S)- or (R)-2-cyclohexen-1-ol by the reaction with the appropriate chiral lithium amide reagent has been evaluated theoretically using the MM3 force field. The plausible possible structures for each precursor (reaction intermediate complex) leading to a (S)- or (R)-2-cyclohexen-1-ol have been optimized with the extended MM3 force field applicable to the lithium amide functional group, and the populations of their (S)- or (R)-reaction intermediate complexes at an ambient temperature (298 K) were calculated. The initial structure for evaluating the reaction intermediates of this asymmetric synthesis was constructed on the basis of the optimized ab initio transition state structure (MP2/6-31+G∗) comprising lithium amide LiNH2 and propene oxide. To the thus obtained transition state structure composed of LiNH2 and propene oxide, the other remaining Cartesian coordinates for the actual reaction intermediates composed of the chiral lithium amides and cyclohexene oxide were added to make the reaction intermediate structure. The conformational search for the reaction intermediate has been carried out by using the Stochastic search Algorithm, and the optimized geometries and their conformational energies (steric energies) have been calculated by the MM3 force field. The populations calculated from the conformational energies of the reaction intermediate leading to the (S)- or (R)-2-cyclohexen-1-ol were shown to be linearly well correlated with the experimentally reported enantiomer excess (% ee) values. The critical factors to control the enantioselectivity were investigated on the basis of the optimized structures of the reaction intermediate complexes. The MM3 force field approach was shown to be applicable to the theoretical evaluation of the enantioselectivity and be useful for designing a new functional chiral lithium amide reagent for the asymmetric synthesis.
Databáze: OpenAIRE
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