Study of chirality with computational methods

Sabine Schefzick, Purdue University

Abstract

Chirality is influencing our life every second. Chiral molecules, also called enantiomers, can be found everywhere in the world, even within our bodies. A pair of enantiomers will react differently only in a chiral environment thus they initiate, for example different body responses. Accordingly, there exists a clear demand to obtain products in a single enantiomeric form, which can be achieved by either separating the racemic mixture of enantiomers or by producing single enantiomeric product. In this thesis both options are discussed. The first part of the thesis deals with the separation of racemic products. Stochastic Molecular Dynamics simulations were performed to study the chiral recognition process that takes place on a chiral stationary phase (CSP). In-depth analysis unveiled that for cinchona-motif chiral stationary phases, electrostatic interactions are the major contributor for enantiodiscriminations. In addition, it was shown that the fragment most responsible for the stereodiscrimination process is the carbamate group of the chiral selector. A CoMFA study was also performed to assess how the carbamate group could be modified to improve the enantioselectivity of newly designed CSPs. It was found that the most important field for enantiodiscrimination is the steric field. With that in mind, novel and potentially improved CSPs were suggested. The second part of the thesis deals with the production of single enantiomeric products. One way to synthesize single enantiomers involves using asymmetric synthesis, in which an asymmetric catalyst is used for the stereodifferentiating step. A way to quantify chirality (instead of considering chirality as a either/or property of a molecule) was used to establish a relationship between the chirality content of chiral catalysts for a series of reactions and their ability to carry out a stereodifferentiating task (e.g. to induce asymmetry during a chemical reaction). A relationship could be established for biaryl-Ti-complexes and also for bisoxazoline-Cu2+-complexes. During these investigations it was discovered that ligands coordinated to the metal have more chirality than they have in the unbound state. Therefore, several ligand distortion modes were studied to explore the dependence of these distortions and the chirality content of chiral catalyst, and hence the enantiomeric excess of the reaction. It was found that for bisoxazoline-Cu2+-complexes the twisting motion has the largest impact on the chirality content. For the Jacobsen-Katsuki system it was found that twisting and step-induced kinks have the greatest influence of chirality content.

Degree

Ph.D.

Advisors

Lipkowitz, Purdue University.

Subject Area

Analytical chemistry|Physical chemistry|Organic chemistry

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