Selective Catalytic [3+n]-Cycloaddition Reactions with Vinyldiazo Compounds

乙烯基重氮化合物的选择性催化 [3 n]-环加成反应

• 批准号: 1763168
• 负责人: Michael Doyle
• 金额: $ 47万
• 依托单位: University of Texas at San Antonio
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1763168&HistoricalAwards=false
• 关键词: Selective; Catalytic; 3+n; Cycloaddition; Reactions

With this award, the Chemical Catalysis Program of the Division of Chemistry is supporting the research of Professor Michael P. Doyle of the University of Texas at San Antonio. Professor Doyle is developing a class of reactions known as "cycloadditions" that form rings of atoms. These rings are the building blocks of many important compounds, including precursors to biologically active molecules, pharmaceutical drugs, and materials. Professor Doyle has designed chemical systems that are capable of controlling the 3-dimensional shape of the products, a feature that is crucial to the synthesis of molecules of medicinal importance. In addition, some of the these cycloaddition reactions use earth-abundant metals to speed up the reaction. This project provides a training and preparation for the next generation of diverse researchers in the chemical sciences. Undergraduate and graduate students working on this project gain expertise in modern synthetic methods and laboratory techniques while being exposed to an intellectually stimulating and challenging environment that will prepare them for future careers in STEM fields.The cost-effective preparation of complex chiral molecules is directly dependent on the availability of sustainable synthetic methodologies. In this project, Professor Doyle is advancing the discovery and development of catalytic (3+n)-cycloaddition reactions where n=1, 2, or 3, for the synthesis of carbocyclic and heterocyclic compounds. He and his team are using a metal-stabilized three-carbon vinylcarbene that is derived either from a vinyldiazo compound, or a donor-acceptor cyclopropane, to selectively form products containing 4 to 6-membered rings and up to two heteroatoms. Stereoselectivity in these cycloaddition reactions is imparted via chiral ligands, which restrict the approach of a reactant to one side of the vinylcarbene, providing enantiomeric ratios as high as 99:1. The use of earth-abundant copper catalysts, and the use of cyclopropenes as vinylcarbene sources are also actively pursued. There is also a strong commitment to engaging a diverse group of students to carry out this research.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.

有了这个奖项，化学系的化学催化计划正在支持德克萨斯大学圣安东尼奥分校的Michael P. Doyle教授的研究。多伊尔教授正在研究一类称为“环加成”的反应，这种反应可以形成原子环。这些环是许多重要化合物的组成部分，包括生物活性分子、药物和材料的前体。Doyle教授设计了能够控制产品三维形状的化学系统，这一特征对合成具有医学重要性的分子至关重要。此外，这些环加成反应中的一些使用地球上丰富的金属来加速反应。该项目为化学科学的下一代多样化研究人员提供培训和准备。从事该项目的本科生和研究生将获得现代合成方法和实验室技术方面的专业知识，同时将接触到一个智力刺激和具有挑战性的环境，为他们未来在STEM领域的职业生涯做好准备。复杂手性分子的成本效益制备直接取决于可持续合成方法的可用性。在这个项目中，Doyle教授正在推进催化（3+n）-环加成反应的发现和开发，其中n=1，2或3，用于合成碳环和杂环化合物。他和他的团队正在使用一种金属稳定的三碳乙烯基卡宾，该卡宾衍生自乙烯基重氮化合物或供体-受体环丙烷，以选择性地形成含有4至6元环和多达两个杂原子的产物。这些环加成反应中的立体选择性是通过手性配体赋予的，其限制反应物接近乙烯基卡宾的一侧，提供高达99：1的对映体比率。使用地球上丰富的铜催化剂和使用环丙烯作为乙烯基卡宾来源也在积极地进行中。该奖项反映了NSF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。

项目成果

Strain‐Induced Nucleophilic Ring Opening of Donor–Acceptor Cyclopropenes for Synthesis of Monosubstituted Succinic Acid Derivatives

应变诱导供体-受体环丙烯亲核开环用于合成单取代琥珀酸衍生物

• DOI: 10.1002/chem.202003427
• 发表时间: 2020
• 期刊: Chemistry – A European Journal
• 作者: Marichev, Kostiantyn O.;Wang, Kan;Greco, Nicole;Dong, Kuiyong;Chen, Jinzhou;Lei, Jinping;Doyle, Michael P.
• 通讯作者: Doyle, Michael P.

Catalyst Choice for Highly Enantioselective [3 + 3]-Cycloaddition of Enoldiazocarbonyl Compounds

• DOI: 10.1021/acscatal.8b03391
• 发表时间: 2018-09
• 期刊: ACS Catalysis
• 影响因子: 12.9
• 作者: Kostiantyn O. Marichev;Frady G. Adly;Alejandra M. Carranco;Estevan C Garcia;H. Arman;M. Doyle

Catalyst-Directed Divergent Catalytic Approaches to Expand Structural and Functional Scaffold Diversity via Metallo-Enolcarbene Intermediates

• DOI: 10.1021/acscatal.1c01051
• 发表时间: 2021-04-05
• 期刊: ACS CATALYSIS
• 影响因子: 12.9
• 作者: Dong, Kuiyong;Zheng, Haifeng;Doyle, Michael P.
• 通讯作者: Doyle, Michael P.

Brønsted Acid Catalyzed Friedel–Crafts‐Type Coupling and Dedinitrogenation Reactions of Vinyldiazo Compounds

布伦斯台德酸催化乙烯基重氮化合物的 Friedel Crafts 型偶联和脱二氮反应

• DOI: 10.1002/anie.202004328
• 发表时间: 2020
• 期刊: Angewandte Chemie International Edition
• 作者: Zheng, Haifeng;Dong, Kuiyong;Wherritt, Daniel;Arman, Hadi;Doyle, Michael P.
• 通讯作者: Doyle, Michael P.

Chiral donor–acceptor azetines as powerful reactants for synthesis of amino acid derivatives

• DOI: 10.1038/s41467-019-13326-8
• 发表时间: 2019-11
• 期刊: Nature Communications
• 影响因子: 16.6
• 作者: Kostiantyn O. Marichev;Kuiyong Dong;Lynée A. Massey;Yongming Deng;Luca De Angelis;Kan Wang;H. Arman;M. Doyle