One of the most difficult problems in the preparation of medicinal agents on the laboratory or industrial scale is the control of stereochemistry and in particular the preparation of enantiomerically pure compounds. One of the most dramatic examples of the importance of chirality control was the use of the drug thalidomide, which was manufactured and sold as a racemic mixture. One optical isomer produced the desire therapeutic effect, while the enantiomer, which was assumed to be pharmacologically inert, led to fetal deformities. Because of dramatic differences in pharmacological effects that enantiomers can produce it is likely that all future drugs that contain chiral centers will be sold as only the desired therapeutically active enantiomer. Transition metal organometallic complexes are widely utilized to efficiently catalyze organic transformations on both the laboratory and industrial scale. There is tremendous potential for using chiral organometallic complexes to carry out enantioselective transformations. However, a major hurdle that has prevented chiral catalysis from fulfilling this potential has been the lack of readily available enantiomerically pure organometallic complexes.
The aims of this project are to prepare enantiomerically pure chiral substituted tetramethylcyclopentadienyl ligands and enantiomerically pure chiral bridged cyclopentadienyl ligands, and to utilize these new enantiomerically pure chiral ligands to prepare new chiral group IV transition metal complexes. We will then examine the potential of these new chiral group IV transition metal complexes to carry out stoichiometric and catalytic enantioselective organic synthesis, with the aim of developing methodologies that can be applied to the synthesis of enantiomerically pure medicinal agents.
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