New ligands, reagents and strategies for asymmetric synthesis

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The proposed research is aimed at developing new methods for the synthesis of chiral compounds.  Since the chirality or handedness of a drug can have a major impact on its biological activity, it is important to make potential drugs either entirely left-handed or right-handed.  The focus will be on creating new reagents to carry out transformations which are not currently possible using existing methodology or have significant advantages over existing methodology.We will examine new ways in which we can prepare organic compounds with defined stereochemistry.  An emphasis will be placed on developing carbon-carbon bond forming reactions which use only a catalytic amount of chiral ligands.  The simultaneous construction of the carbon framework along with establishing the absolute stereochemistry of organic molecules is inherently efficient.  We were the first to show that this approach to asymmetric synthesis is possible using ligand exchange on alkynylboronates.  An obvious advantage of this approach is that only sub-stoichiometric amounts of ligands are required.  A less obvious aspect is that processes could be developed using this approach that will avoid the use of heavy metals, an important consideration in the preparation of pharmaceuticals and as chemists become more environmentally conscientious.  We will now expand this chemistry to other reagents and substrates.  New ligands tailored to optimize reactivity and selectivity will be prepared; these may be useful in these reactions or other asymmetric processes.  Overall, the research will lead to new methods for the preparation of stereochemically-defined organic molecules as well as to a better understanding of how stereochemistry can be controlled using chiral ligands.