New ligands, reagents and strategies for asymmetric synthesis

本研究旨在开发手性化合物合成的新方法。由于药物的手性或手性对其生物活性有重大影响，因此将潜在药物完全制成左手性或右手性是很重要的。重点将是创造新的试剂来进行目前使用现有方法无法实现的转化，或者比现有方法具有显著的优势。我们将研究新的方法来制备具有明确立体化学性质的有机化合物。重点将放在发展碳碳键形成反应，只使用催化量的手性配体。碳框架的同时构建和有机分子的绝对立体化学的建立本身是高效的。我们是第一个证明这种不对称合成方法是可能的，利用配体交换在炔基硼酸盐。这种方法的一个明显优点是只需要亚化学计量量的配体。一个不太明显的方面是，可以使用这种方法开发工艺，避免使用重金属，这是制备药物的一个重要考虑因素，化学家们越来越注重环境。现在我们将把这个化学扩展到其他试剂和底物。将制备新的配体，以优化反应性和选择性；这些可能在这些反应或其他不对称过程中有用。总的来说，这项研究将为制备立体化学定义的有机分子提供新的方法，并更好地理解如何使用手性配体来控制立体化学。

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.