Understanding stereoinduction in catalysis via computer: New tools for asymmetric synthesis

An overview of new concepts, new algorithms, and new computational protocols directed at synthetic chemists interested in generating chiral catalysts is presented in this report. A new mapping tool called stereocartography is described, which allows one to locate the most stereoinducing region around a proposed catalyst. Extant QSAR methods including Comparative Molecular Field Analysis (CoMFA) and a new technique called QM-QSAR are tools for modeling stereoinduction and for making predictions about whether a proposed chiral catalyst will be effective or not. Database mining with the intention of locating unbiased, unique ligand motifs for use in catalysis is described. Functionality mapping of transition states is introduced with the idea of locating where around that transition structure, functional groups assist or interfere with a given reaction coordinate. Functionality mapping in combination with database mining is shown to be an effective way to generate new catalysts for asymmetric induction. Beyond these new tools, more advanced treatments of chirality are investigated - the relationship between the chirality content of a catalyst and its ability to induce asymmetry is discussed along with the concept of distorting a ligand to make it more or less chiral.