Enantioselective Organic Syntheses (Chemistry)

有机合成领域的持续挑战是开发具有普遍性的合成反应，但又表现出很高的选择性。莫兰德博士发现了一种方法，可以利用一种古老的反应，即所谓的Reformatsky反应，极大地提高了它在合成复杂天然产物（如β -内酰胺类抗生素）中的用途。本课题属于有机与大分子化学项目。这将开发出复杂的、对映体纯有机底物的新条目。研究的第一个方面将探索利用二碘化钐诱导的分子内Reformatsky反应。该方法的全面发展将允许在碳-碳键形成过程中通过1,3-不对称诱导获得syn 1,3-二醇。HMG-CoA还原酶抑制剂的快速生成是这一进展将允许的许多重要贡献之一。研究人员还计划将其应用于含氮底物，这方面的研究将为开发具有重要药理学意义的氨基糖苷类和β -内酰胺类抗生素提供重要的新途径。基于二碘化钐还原乙烯基氧环烷的化学反应包括研究的第二个方面。由这一过程产生的烯丙醇将被纳入几种天然产物的合成中，包括白三烯B4。另一种独特的1,3-不对称诱导方法是在分子内将钐基Reformatsky试剂Michael加成到共轭烯烃上。一种新型环丙烷化试剂Sm/CH2I2将被深入研究，以确定其在有机合成中的独特作用，利用烯丙醇作为底物在该领域的研究的第一个方面。手性环氧化合物的立体控制环化是制备手性碳环和杂环底物的另一种方法。利用烷基硼酸盐和烯丙基硅烷的反应将被探索，以提供获得有机分子的途径，其中多达三个连续的立体中心以完全可预测的方式被控制。最后，探讨环氧阴离子的化学性质。这些独特的亲核试剂可能会彻底改变多功能环氧化物官能团与有机分子结合的方式。

The continuing challenge in the area of organic synthesis is to develop synthetic reactions that have generality, yet exhibit great selectivity. Dr. Molander has discovered a way to take an old reaction, the so-called Reformatsky reaction, and greatly increase its usefulness in the synthesis of complex natural products like the beta-lactam antibiotics. This project is in the Organic and Macromolecular Chemistry Program. This will develop novel entries into complex, enantiomerically pure organic substrates. The first aspect of the research will explore use of samarium diiodide-induced intramolecular Reformatsky reactions. Full development of this methodology will permit access to syn 1,3-diols by 1,3-asymmetric induction in a carbon-carbon bond-forming process. Facile generation of HMG-CoA reductase inhibitors is one of many important contributions that this advancement will permit. Application to nitrogen-containing substrates is also planned, and important new routes to pharmacologically important aminoglycoside and beta-lactam antibiotics will result from this aspect of the study. Chemistry based upon samarium diiodide reduction of vinyl oxiranes comprises the second aspect of the study. Allylic alcohols generated by this process will be incorporated into several natural products syntheses, including leukotriene B4. Another unique method for 1,3-asymmetric induction is planned, involving intramolecular Michael addition of samarium-based Reformatsky reagents to conjugated olefins. A novel cyclopropanation reagent, Sm/CH2I2, will be thoroughly studied to determine its unique role in organic synthesis, utilizing allylic alcohols as substrates in the first aspect of studies in this area. Stereocontrolled cyclizations onto chiral epoxides constitute another proposed approach to chiral carbocycles and heterocyclic substrates. Reactions utilizing alkynylborates and allylsilanes will be explored to provide access to organic molecules in which up to three contiguous stereocenters are controlled in a completely predictable fashion. Finally, the chemistry of epoxy anions will be explored. These unique nucleophiles may very well revolutionize the manner in which the versatile epoxide functional group is incorporated into organic molecules.