Synthetic Versatility of N-O Bond Rearrangements

通过这一奖项，化学合成计划支持伊利诺伊大学芝加哥分校化学系的Laura L.Anderson教授的研究，以探索新的N-O键重排的设计和应用，以高效和立体选择性地合成新的具有挑战性的有机分子。Anderson团队之前已经为这些类型的转换的价值和多功能性建立了概念证明，并将推动这些合成工具朝着有效制备新的潜在“特权”结构、手性非外消旋化合物和关键的四碳合成子的方向发展。这些进展将对阐明重要药物和材料的新途径产生广泛影响。此外，这项研究中产生的化合物将提交给伊利诺伊大学药物发现中心的化学图书馆，以针对新的生物靶标进行筛选。这个研究项目的机械方法将使研究生和本科生的同事接触到合成有机化学和物理有机化学的元素。国际和平协会将在这里继续努力扩大参与，特别是通过与妇女和本科生合作，鼓励她们考虑在STEM的职业道路。还有一个高中推广部分，旨在向学生介绍化学反应的数据分析。该项目将扩大N-烯基硝酮和O-烯基酮作为关键中间体的使用，以快速有效地合成复杂的有机分子。具体地说，我们将致力于以下目标：1)不对称氢键供体催化将N-烯基硝酮和烯的混合物通过级联过程转化为对映体富集型吲哚杂环；2)N-烯基硝酮的电环化和[4 2]-环加成反应条件将被优化以合成新的吗啉基杂环；3)将通过铜介导的偶合和重排方法探索模块化和立体选择性地合成1，4-亚氨基酮的方法。此外，机理研究将被用来阐明Chan-Lam反应合成N-烯基硝酮和O-烯基肟的化学选择性的来源，以便于获得更广泛的模块底物进行重排。这些目标的实现将通过为反合成分析提供新的工具，并通过获得新的结构基序来扩大化学空间，从而促进合成化学的发展。

With this award, the Chemical Synthesis Program is supporting the research of Professor Laura L. Anderson of the Department of Chemistry at the University of Illinois at Chicago to explore the design and application of new N-O bond rearrangements for the efficient and stereoselective synthesis of new and challenging organic molecules. The Anderson group has previously established the proof of concept for the value and versatility of these types of transformations and will advance these synthetic tools toward the efficient preparation of new potentially "privileged" structures, chiral non-racemic compounds, and key four-carbon synthons. These advances will have a broad impact on the elucidation of new pathways to important pharmaceuticals and materials. Furthermore, the compounds generated in this study will be submitted to the chemical library at the UICentre for Drug Discovery to be screened against new biological targets. The mechanistic approach to this research program will expose graduate and undergraduate student co-workers to elements of both synthetic and physical organic chemistry. The PI will continue here efforts to broaden participation, particularly by working with women and undergraduate students to encourage them to consider career paths in STEM. There is also a high school outreach component designed to introduce students to data analysis of chemical reactions.This project will expand the use of N-alkenyl nitrones and O-alkenyl oximes as key intermediates in the rapid and efficient synthesis of complex organic molecules. Specifically, the following goals will be pursued: 1) asymmetric hydrogen-bond-donor catalysis will be used to convert mixtures of N-alkenyl nitrones and allenes to enantioenriched indole-based heterocycles through a cascade process whose selectivity can be controlled through a balance of solvent effects; 2) conditions for the electrocyclization and [4+2]-cycloaddition of N-alkenyl nitrones will be optimized for the synthesis of new morpholine-based heterocycles and 3) methods for the modular and stereoselective synthesis of 1,4-iminoketones will be explored through a copper-mediated coupling and rearrangement approach. In addition, mechanistic studies will be used to elucidate the origin of the chemoselectivity of the Chan-Lam reaction for the synthesis of N-alkenyl nitrones and O-alkenyl oximes to facilitate access to a wider variety of modular substrates for rearrangement. Completion of these goals will advance synthetic chemistry by providing new tools for retrosynthetic analysis and expanding chemical space through access to new structural motifs.