Asymmetric Hydrogenations of Unfunctionalized Alkenes Mediated by Ir-N-Heterocyclic Carbene Complexes

本研究的重点将是使用半理性的方法来设计催化剂。氨基酸的杂环衍生物将通过结合较小的构建块库来制备大的配体库。其次，将研究几种关键烯烃的加氢反应，包括新的底物（环丙烯、环丁烯、四取代烯烃），以说明该方法的普遍性，并提供不易通过其他方法制备的产品。此外，将制备含有有用的1,1-二取代烯烃的常见甾体侧链的chiron，但工作的重点将是发展导致1,3-二甲基化和1,3,5-三甲基化chirons的反应。这些都是天然产物合成中的重要结构，并且所提出的加氢路线可能优于目前使用的不对称烷基化策略。通过这个奖项，有机和大分子化学项目支持了德克萨斯农工大学化学系凯文·伯吉斯博士的研究。伯吉斯教授将把他的工作重点放在非官能化烯烃的不对称加氢方法的发展上。经济的、面向多样性的配体合成将得到发展，这样配合物的文库就可以很容易地用不同的底物进行筛选。此外，广泛的底物将被研究，重点是那些导致真正有用的chirons。这项工作有可能对制药业产生更广泛的影响，该项目是培养本科生、研究生和博士后的绝佳场所。

The focus of this research will be to use a semi-rational approach to catalyst design. Heterocyclic derivatives of amino acids would be used to prepare large libraries of ligands by combining smaller libraries of building blocks. Second, hydrogenations of several key alkenes would be examined including novel substrates (cyclopropenes, cyclobutenes, a tetrasubstituted alkene) will be examined to illustrate the generality of the method and to provide products that are not easy to prepare via other methods. Also, a chiron for a common steroidal side-chain containing a useful 1,1-disubstituted alkene will be prepared, but the emphasis of the work would be toward developing reactions that lead to 1,3-di- and 1,3,5-trimethylated chirons. These are important structures in natural product syntheses, and the proposed hydrogenation route is potentially superior to the asymmetric alkylation strategies that are currently in use. With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Kevin Burgess in the Department of Chemistry at Texas A&M University. Professor Burgess will focus his work on the development of methodology for the asymmetric hydrogenation of unfunctionalized alkenes. Economical, diversity-oriented ligand syntheses will be developed so that libraries of complexes become readily accessible for screening with different substrates. Also, a great range of substrates will be studied, focused on those that lead to genuinely useful chirons. The work has potential for broader impact in the pharmaceutical industry and the project serves as an excellent venue for the training of undergraduates, graduate students and postdoctorals.