Harnessing Nonclassical Metal-Arene Interactions to Achieve Enantioselective Catalysis

美国国家科学基金会化学部的化学催化计划支持北得克萨斯大学的勒格兰德·M·斯劳特教授进行旨在利用金属与手性配体上的芳香族基团的非经典相互作用来实现对映选择性催化的研究。这些鲜为人知的二次相互作用可能会增加手性催化剂设计中通常采用的空间相互作用，潜在地导致传统手性配体无法实现的高度对映选择性反应。这项研究将使用一组新的手性联萘合成子来创建手性无环二胺卡宾和亚膦配体，这些配体优化为支持金属-芳烃相互作用。这些相互作用促进合成有用的对映选择性反应的能力，包括碳-碳多键的氢功能化，不对称的碳-碳偶联和电环化，将被研究。结构、光谱和计算研究将探索金属-芳烃弱相互作用的性质及其在催化中的作用，重点是具有催化作用的重要金属钯和金。从廉价的非手性前体合成手性、医学上重要的复杂分子的新催化方法是本研究的预期结果。合成手性分子的能力非常重要，因为药物分子的两个对映体或镜像对人体有非常不同的影响。这项研究可以提供新的工具来制备作为单一对映体的复杂分子，以新手性药物前体的形式潜在地为社会提供显著的好处。这些研究将与一个名为“催化剂的魔力”的推广项目密切相关，该项目将利用动手实验向中学生介绍以催化为重点的研究和科学概念。美国原住民学生比例较高的学校将在公共教育领域老牌合作者的帮助下成为目标，目标是扩大美国原住民对可能导致获得高等教育和科学职业的活动的参与。金属-芳烃相互作用作为实现对映选择性催化的新主题的发展，可能会对合成有用分子的技术产生革命性的影响，因为它促进了对过渡金属催化中鲜为人知的二次相互作用作用的进一步研究。

The Chemical Catalysis Program in the Chemistry Division at the National Science Foundation supports Professor LeGrande M. Slaughter of the University of North Texas, for studies aimed at utilizing nonclassical interactions of metals with aromatic groups on chiral ligands to achieve enantioselective catalysis. These poorly-understood secondary interactions could augment the steric interactions typically employed in chiral catalyst design, potentially leading to highly enantioselective reactions that are not achievable with conventional chiral ligands. The research will use a set of new chiral binaphthyl synthons to create chiral acyclic diaminocarbene and phosphinite ligands that are optimized to support metal-arene interactions. The ability of these interactions to promote synthetically useful enantioselective reactions, including hydrofunctionalizations of carbon-carbon multiple bonds, asymmetric carbon-carbon couplings, and electrocyclizations, will be investigated. Structural, spectroscopic, and computational studies will probe the nature of weak metal-arene interactions and their role in catalysis, focusing on the catalytically important metals palladium and gold. New catalytic methods for the synthesis of chiral, medicinally important complex molecules from inexpensive achiral precursors are an expected outcome of this research. The ability to synthesize chiral molecules in enantiomerically pure form is important, because the two enantiomers or 'mirror images' of a drug molecule can have very different effects on the human body. This research could provide new tools to prepare complex molecules as pure single enantiomers, potentially providing significant benefits to society in the form of new chiral drug precursors. These studies will be closely tied to an outreach program entitled 'The Magic of Catalysts' that will use hands-on experimentation to introduce middle school students to concepts of research and science using catalysis as a focus. Schools with high percentages of Native American students will be targeted with the help of established collaborators in public education, with a goal of broadening participation of Native Americans in activities that could lead to attainment of higher education and careers in science. The development of metal-arene interactions as a novel motif for achieving enantioselective catalysis could have a transformative impact on technologies for the synthesis of useful molecules by stimulating further study of the little-investigated role of secondary interactions in transition metal catalysis.