Synthetic Versatility of N-O Bond Rearrangements

N-O 键重排的合成多功能性

• 批准号: 1464115
• 负责人: Laura Anderson
• 金额: $ 42万
• 依托单位: University of Illinois at Chicago
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1464115&HistoricalAwards=false
• 关键词: Synthetic; Versatility; Bond; Rearrangements

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.

有了这个奖项，化学合成计划是支持教授劳拉L。芝加哥的伊利诺伊大学化学系的安德森，探索新的N-O键重排的设计和应用，以有效和立体选择性地合成新的具有挑战性的有机分子。 安德森小组先前已经建立了这些类型的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二氢吡喃。 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，本研究中产生的化合物将提交给UICentre药物发现的化学图书馆，以针对新的生物靶点进行筛选。 该研究计划的机械方法将使研究生和本科生同事接触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。 此外，还有一个高中外展部分，旨在向学生介绍化学反应的数据分析。该项目将扩大N-烯基硝酮和O-烯基肟作为快速有效合成复杂有机分子的关键中间体的用途。 具体而言，将追求以下目标：1）不对称氢键供体催化将用于通过级联过程将N-烯基硝酮和联烯的混合物转化为对映体富集的基于吲哚的杂环，该级联过程的选择性可以通过溶剂效应的平衡来控制; 2）N-烯基硝酮的电环化和[4+2]-环加成反应的条件将被优化，以合成新的基于吗啉的杂环;将通过铜介导的偶联和重排方法探索1，4-亚氨基酮的模块化和立体选择性合成方法。 此外，机械的研究将被用来阐明的起源的Chan-Lam反应的N-烯基硝酮和O-烯基肟的合成，以促进获得更广泛的各种模块化底物重排的化学选择性。 这些目标的完成将通过提供新的逆合成分析工具和通过获得新的结构基序扩展化学空间来推进合成化学。