Synthetic Versatility of N-O Bond Rearrangements

通过这一奖项，化学合成项目支持了芝加哥伊利诺伊大学化学系的劳拉·l·安德森教授的研究，她探索了新的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和具有挑战性的有机分子。Anderson小组先前已经建立了这些类型转化的价值和多功能性的概念证明，并将推进这些合成工具，以有效地制备新的潜在的“特权”结构，手性非外消旋化合物和关键的四碳合成子。这些进展将对阐明重要药物和材料的新途径产生广泛的影响。此外，本研究生成的化合物将提交给uiccentre for Drug Discovery的化学文库，用于针对新的生物靶点进行筛选。这个研究项目的机械方法将使研究生和本科生同事接触到合成和物理有机化学的元素。PI将继续努力扩大参与，特别是通过与女性和本科生合作，鼓励他们考虑STEM的职业道路。还有一个高中拓展部分，旨在向学生介绍化学反应的数据分析。该项目将扩大n -烯基硝基和o -烯基肟作为快速高效合成复杂有机分子的关键中间体的使用。具体而言，将追求以下目标：1)不对称氢键供体催化将用于将n-烯基硝基和烯基的混合物通过级联过程转化为富集对映体的吲哚基杂环，其选择性可以通过平衡溶剂效应来控制；2)优化n -烯基硝基酮的电环化和[4+2]-环加成条件，以合成新的基于morpholin的杂环化合物；3)通过铜介导的偶联和重排方法探索模块化和立体选择性合成1,4-亚胺酮的方法。此外，机理研究将用于阐明合成n-烯基硝基和o -烯基肟的Chan-Lam反应的化学选择性的起源，以促进获得更广泛的模块化底物进行重排。这些目标的完成将为反合成分析提供新的工具，并通过获取新的结构基序来扩大化学空间，从而推动合成化学的发展。

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.