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Discovering Modular Catalysts for Asymmetric Synthesis with Computation

通过计算发现用于不对称合成的模块化催化剂

基本信息

批准号：
1955876
负责人：
Robert Paton
金额：
$ 42.08万
依托单位：
Colorado State University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2024-05-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1955876&HistoricalAwards=false
关键词：
Discovering Modular Catalysts Asymmetric Synthesis

项目摘要

Dr. Robert Paton of the Department of Chemistry at Colorado State University is supported by an award from the Chemical Catalysis program in the Division of Chemistry to develop new computational approaches for chiral catalyst discovery. The preparation of chiral molecules plays a vital and enabling role in the discovery of medicines, agrochemicals, and materials. Newly approved drugs are dominated by single enantiomer, chiral compounds. Dr. Paton’s group develops new methods of theory and simulation to accelerate the discovery of new catalysts and new reactions for the highly-selective construction of chiral molecules. This will go hand-in-hand with new mechanistic discoveries and collaborations with experimentalists that broaden the horizons of participating scientists. The research team, which will include undergraduate and postgraduate researchers, will learn a diverse array of skills well-aligned with the modern STEM workplace and will engage the public through outreach events in Colorado.There is a widely recognized need for rational approaches to replace empirical screening in the discovery of new catalyst structures. In this project, Dr. Robert Paton is developing computational protocols that combine small-molecule fragments adhering to the synthetic logic of known coupling reactions to construct and optimize catalyst architectures for asymmetric transformations. Virtual catalyst libraries are being assembled and mapped in an automated fashion using computational chemistry descriptions of steric and electronic properties. A triaged approach is being developed that directs in-depth quantum chemical efforts towards the most profitable areas of catalyst space to promote enantioselective hydrogen-bonding phase-transfer catalysis, bifunctional organocatalysis, and transformations involving metal-phosphoramidite complexes. In each case, new mechanistic discoveries are revealing the structural pre-requisites for catalytic activity and high enantioselectivity for a given substrate. The automated construction of large catalyst libraries, and the computation of steric and electronic parameters are providing that large datasets of use to the broader community.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.

科罗拉多州立大学化学系的Robert Paton博士得到化学系化学催化项目的支持，为手性催化剂发现开发新的计算方法。手性分子的制备在药物、农用化学品和材料的发现中起着至关重要的作用。新批准的药物主要是单一对映体，手性化合物。佩顿博士的团队开发了新的理论和模拟方法，以加速发现用于高选择性构建手性分子的新催化剂和新反应。这将伴随着新的机械发现和与实验者的合作，从而拓宽参与其中的科学家的视野。研究团队将包括本科生和研究生研究人员，他们将学习与现代STEM工作场所很好地结合的各种技能，并将通过科罗拉多州的外展活动吸引公众。人们普遍认为，在发现新的催化剂结构方面，需要理性的方法来取代经验筛选。在这个项目中，Robert Paton博士正在开发计算协议，将遵循已知偶联反应的合成逻辑的小分子片段组合在一起，以构建和优化不对称转化的催化剂结构。虚拟催化剂库正在使用空间和电子性质的计算化学描述以自动化的方式进行组装和映射。正在开发一种分类的方法，将深入的量子化学努力引导到最有利可图的催化剂空间区域，以促进对映选择性氢键相转移催化、双功能有机催化和涉及金属-亚磷酰胺络合物的转化。在每一种情况下，新的机理发现都揭示了特定底物的催化活性和高对映选择性的结构先决条件。大型催化剂库的自动化构建以及空间和电子参数的计算正在为更广泛的社区提供使用的大型数据集。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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

期刊论文数量（21）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

AQME: Automated quantum mechanical environments for researchers and educators

DOI：
10.1002/wcms.1663
发表时间：
2023-02-26
期刊：
WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE
影响因子：
11.4
作者：
Alegre-Requena, Juan V.;Shree, Sowndarya S., V;Paton, Robert S.
通讯作者：
Paton, Robert S.

Pd-Catalyzed Asymmetric Amination of Enamines: Expedient Synthesis of Structurally Diverse N–C Atropisomers

DOI：
10.1021/acscatal.3c00732
发表时间：
2023-05
期刊：
ACS Catalysis
影响因子：
12.9
作者：
P. Zhang;Changsheng Guo;Wang Yao;Chuan-Jun Lu;Yingzi Li;R. Paton;Ren-Rong Liu
通讯作者：
P. Zhang;Changsheng Guo;Wang Yao;Chuan-Jun Lu;Yingzi Li;R. Paton;Ren-Rong Liu

Asymmetric Azidation under Hydrogen Bonding Phase-Transfer Catalysis: A Combined Experimental and Computational Study.

DOI：
10.1021/jacs.1c13434
发表时间：
2022-03-16
期刊：
Journal of the American Chemical Society
影响因子：
15
作者：
Wang J;Horwitz MA;Dürr AB;Ibba F;Pupo G;Gao Y;Ricci P;Christensen KE;Pathak TP;Claridge TDW;Lloyd-Jones GC;Paton RS;Gouverneur V
通讯作者：
Gouverneur V

Halogenation of the 3-position of pyridines through Zincke imine intermediates.

DOI：
10.1126/science.add8980
发表时间：
2022-11-18
期刊：
Science (New York, N.Y.)
影响因子：
0
作者：
通讯作者：

Mechanistic Aspects on [3+2] Cycloaddition (32CA) Reactions of Azides to Nitroolefins: A Computational and Kinetic Study

[3 2] 叠氮化物与硝基烯烃的环加成 (32CA) 反应的机理：计算和动力学研究

DOI：
10.1002/chem.202202294
发表时间：
2022
期刊：
Chemistry – A European Journal
影响因子：
0
作者：
Kawamura, Meire Y.;Alegre‐Requena, Juan V.;Barbosa, Thaís M.;Tormena, Cláudio F.;Paton, Robert S.;Ferreira, Marco A. B.
通讯作者：
Ferreira, Marco A. B.