DESIGNING LIGANDS USING COMPUTATIONAL TECHNIQUES

非对映体和对映选择性化学反应对于高效合成复杂的手性目标是必不可少的，包括天然产物、新型材料、生物探针和药物。虽然对不对称过程的传统方法依赖于直觉或随机筛选方法，但使用计算技术来开发新的和改进的方法仍有待开发。我们的总体目标是开发一系列合理的设计方案，用于鉴定用于重要合成反应的新型手性助剂和催化剂，这些助剂和催化剂通过很好地描述过渡态进行。特别是，我们正在使用一种通过计算筛选并入大型结构数据库(如剑桥结构数据库)的数据来识别Noel配体家族的过程。作为这个项目的一部分，我们打算证明过渡态能量的高水平从头计算可以定期与溶液相反应性相关联；这样的结果将在反应发展中提供一个宝贵的工具。该项目的成功可能会极大地改变手性配体的设计方式；即使在组合环境中也是如此，在组合环境中，可以选择经过优化后具有很高成功概率的新型核心支架。

Diastereo- and enantioselective chemical reactions have become essential for the efficient synthesis of complex chiral targets, including natural products, novel materials, biological probes, and pharmaceuticals. While the conventional approach toward asymmetric processes has relied upon intuitive or random screening approaches, the use of computational techniques to develop novel and improved methods has yet to be exploited. Our overall aim is to develop a series of rational design protocols for the identification of new chiral auxiliaries and catalysts for important synthetic reactions, that proceed through well delineated transition-states. In particular, we are using a process that identified noel ligand families via computational screening of data incorporated within large structural databases such as Cambridge Structural Database. As part of this program, we intend to demonstrate that high level ab initio calculations of transition state energies can be correlated to solution phase reactivity on a regular basis; such a result would provide an invaluable tool in reaction development. The success of this program could dramatically change the way chiral ligands are designed; even in a combinatorial setting, where novel core scaffolds could be selected that had a high probability of success upon optimization.