Anionic and Pericyclic Reaction Cascades for Organic Synthesis

在化学系化学合成项目的支持下，亚利桑那大学的Njardarson教授正在研究新的化学反应类别，这些化学反应将导致更有效的方法来制造对社会重要的化合物，如药物制剂、农用化学品和先进材料。从研究中获得的见解将包括强大的多键形成“级联”反应，能够快速生成各种感兴趣的分子，预计将为未来的合成设计实践提供信息。资助项目的更广泛影响还包括参与研究的学生同事的教育和培训，并扩展到使Njardarson教授能够继续为公众开发创新和免费获取的教育内容。在这方面，该奖项将支持扩展PI流行的应用程序和网站“化学设计（CByD）”上的内容，同时将当前和未来的内容转换为机器可读的格式，该格式应与化学合成领域新兴的人工智能/信息学技术兼容。由Njardarson集团制作的关于药物结构和性质的“前200名”系列海报将继续制作，并每年以传统和新的自定义内容格式提供。该项目将包括对Njardarson小组最近引入的新型反离子依赖阴离子不对称氨基- cope重排的持续和显著扩展的研究。这个多功能的反应平台提供了从现成的起始材料获得一系列复杂的富含对映体的手性产物（环和非环分子）；然而，在充分认识到这种方法的力量之前，关于它的范围还有很多需要了解的地方。新的工作将包括建立选择性捕获和开发手性酰胺中间体的方法，以及研究许多可能的原位环化情景。这些努力还将包括简化合成所需的氨基- cope前体（共轭手性亚胺）的新方法，同时还将探索可能胜过氨基- cope反应的新的有用级联的发现。该资助项目的第二部分重点是开发用于组装高价值密集取代的芳香结构（如吡啶、异喹啉和其他芳烃）的新转化，从简单的无环构建块到周环中心反应级联。预计将出现一些重要的新的和有用的方法，用于从简单的起始材料中制备受追捧的无环和有环产品。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

With the support of the Chemical Synthesis Program in the Division of Chemistry, Professor Njardarson of The University of Arizona is studying new classes of chemical reactions that will lead to more efficient methods for the manufacture of compounds of importance to society, such as pharmaceutical agents, agrochemicals, and advanced materials. The insights gained from the studies, which will encompass powerful multiple bond-forming 'cascade' reactions capable of rapidly generating all manner of molecules of interest, are anticipated to inform on the future practice of synthetic design. The broader impacts of the funded project also include the education and training of the student coworkers taking part in the research and extend to enabling Prof. Njardarson's continued development of innovative and freely accessible educational content for the general public. In this regard, the award will support an expansion to the content available on the PI's popular app and website 'Chemistry By Design (CByD)', with concurrent transformation of current and future content to a machine-readable format that should be compatible with emerging artificial intelligence/informatics technologies in the chemical synthesis field. The well-established "Top 200" family of posters form the Njardarson group on the structures and properties of pharmaceutical drugs will continue to be produced and made available annually in traditional and new custom content formats.This project will involve continued and significantly expanded investigations of the new class of counterion-dependent anionic asymmetric amino-Cope rearrangements recently introduced by the Njardarson group. This versatile reaction platform affords access to a range of complex enantioenriched chiral products (both cyclic and acyclic molecules) from readily available starting materials; however, much remains to be learned about its scope before the power of the approach can be fully realized. New work will include establishing methods for the selective trapping and exploitation of chiral enamide intermediates and studying the many possible in situ cyclization scenarios. These efforts will also include novel ways to streamline synthesis of the requisite amino-Cope precursors (conjugated chiral imines) while also exploiting the discovery of new useful cascades that may outcompete the amino-Cope reaction. The second part of the funded project is focused on the development of new transformations for the assembly of high value densely substituted aromatic structures such as pyridines, isoquinolines, and other arenes, from simple acyclic building blocks via pericyclic-centered reaction cascades. It is anticipated that a number of significant new and useful methods for the elaboration of sought after acyclic and cyclic products from simple starting materials, will emerge from the research program.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.