Design, Development and Exploration of New Chiral Spirocyclic Ligands and Catalysts for Asymmetric Catalysis

新型手性螺环配体和不对称催化催化剂的设计、开发和探索

• 批准号: 1955069
• 负责人: Pavel Nagorny
• 金额: $ 38万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 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: 2020-08-15 至 2023-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1955069&HistoricalAwards=false
• 关键词: Design; Development; Exploration; New; Chiral

With this award, the Chemical Catalysis Program of the NSF Division of Chemistry is supporting the research of Dr. Pavel Nagorny of the Department of Chemistry at the University of Michigan. Dr. Nagorny and his research team are developing catalyst scaffolds that can control how molecules interact to produce favored enantiomeric products. Enantiomers are molecules that have similar structures but are mirror images of each other (i.e. a right hand and a left hand). Different enantiomers can have distinct characteristics including therapeutic potency and properties, which is why there is a critical need for catalysts that can selectively form these molecules. The Nagorny research group has previously identified a new type of catalyst that is highly active towards controlling enantioselectivity and is easily tunable towards new types of reactions. Professor Nagorny and his students are currently investigating how these catalysts work and optimizing them for the synthesis of compound fragments that are currently found in bioactive molecules. In addition, the Nagorny group is developing heterogeneous analogues of these catalysts to improve recyclability and sustainability. These studies are being used to train a diverse group of graduate and undergraduate students. Professor Nagorny and his students are also developing instructional safety videos to improve the learning experience of students at the University of Michigan and beyond.Improvements in asymmetric catalysis are critically important for the synthesis of bioactive molecules. To address this need, Dr. Pavel Nagorny and his research group are expanding the repertoire of existing spirocyclic ligands for iridium-catalyzed hydrogenations by exploring a new C2-symmetric chiral scaffold (SPIROL). These ancillary groups possess the key structural features found in the most popular and best-performing chiral spirocyclic ligands and catalysts, but are also easy to synthesize and tune. Simultaneously, the Nagorny group is also working to improve the process efficiency and sustainability associated with the use of spirocyclic catalysts by developing immobilized variants. Immobilized chiral spirocyclic phosphoric acids are being optimized for asymmetric transformations in continuous flow. These studies are advancing tools and processes needed to accelerate asymmetric synthesis.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.

凭借该奖项，美国国家科学基金会化学部的化学催化项目正在支持密歇根大学化学系 Pavel Nagorny 博士的研究。纳戈尔尼博士和他的研究团队正在开发催化剂支架，可以控制分子如何相互作用以生产受欢迎的对映体产品。对映体是具有相似结构但互为镜像的分子（即右手和左手）。不同的对映体可能具有不同的特征，包括治疗效力和性质，这就是为什么迫切需要能够选择性形成这些分子的催化剂。纳戈尔尼研究小组此前发现了一种新型催化剂，该催化剂对于控制对映选择性具有高度活性，并且易于调节以适应新型反应。纳戈尔尼教授和他的学生目前正在研究这些催化剂的工作原理，并优化它们以合成目前在生物活性分子中发现的化合物片段。此外，纳戈尔尼集团正在开发这些催化剂的多相类似物，以提高可回收性和可持续性。这些研究被用来培训不同的研究生和本科生群体。纳戈尔尼教授和他的学生还在制作教学安全视频，以改善密歇根大学及其他地区学生的学习体验。不对称催化的改进对于生物活性分子的合成至关重要。为了满足这一需求，Pavel Nagorny 博士和他的研究小组正在通过探索新的 C2 对称手性支架 (SPIROL) 来扩展现有的用于铱催化氢化的螺环配体。这些辅助基团具有最流行和性能最好的手性螺环配体和催化剂中发现的关键结构特征，但也易于合成和调整。同时，纳戈尔内小组还致力于通过开发固定化变体来提高与使用螺环催化剂相关的工艺效率和可持续性。固定化手性螺环磷酸正在针对连续流中的不对称转化进行优化。这些研究正在推进加速不对称合成所需的工具和流程。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力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

Synthesis and Evaluation of C2-Symmetric SPIROL-Based bis-Oxazoline Ligands

基于 SPIROL 的 C2 对称双恶唑啉配体的合成和评价

• DOI: 10.3390/sym13091667
• 发表时间: 2021-09
• 期刊: Symmetry
• 作者: Sun, Siyuan;Diaz, Nicolas A.;Nagorny, Pavel
• 通讯作者: Nagorny, Pavel

Synthesis of (((1R,3S,3'S)-3,3'-Diethyl-3H,3'H-1,1'-spirobi[isobenzofuran]-7,7'-diyl)bis(oxy))bis(diphenylphosphane)

(((1R,3S,3S)-3,3-二乙基-3H,3H-1,1-螺二[异苯并呋喃]-7,7-二基)双(氧基))双(二苯基膦)的合成

• DOI: 10.15227/orgsyn.099.0190
• 发表时间: 2022-01
• 期刊: Organic Syntheses
• 影响因子: 0.7
• 作者: Sun; Siyuan
• 通讯作者: Siyuan

Enantioselective Parallel Kinetic Resolution of Aziridine-Containing Quinoxalines via Chiral Phosphoric Acid-Catalyzed Transfer Hydrogenation

手性磷酸催化转移氢化对映选择性平行动力学拆分含氮丙啶的喹喔啉

• DOI: 10.1021/acs.orglett.3c03072
• 发表时间: 2023-10
• 期刊: Organic Letters
• 影响因子: 5.2
• 作者: Jhang, Yin;Zhelavskyi, Oleksii;Nagorny, Pavel
• 通讯作者: Nagorny, Pavel

Asymmetric Transfer Hydrogenation of Heterocyclic Compounds in Continuous Flow Using an Immobilized Chiral Phosphoric Acid as the Catalyst

使用固定化手性磷酸作为催化剂连续流动杂环化合物的不对称转移氢化

• DOI: 10.1055/a-2085-5256
• 发表时间: 2023-07
• 期刊: Synthesis
• 作者: Zhelavskyi, Oleksii;Jhang, Yin;Nagorny, Pavel
• 通讯作者: Nagorny, Pavel

Synthesis of Chiral Aziridine Ligands for Asymmetric Alkylation with Alkylzincs: Diphenyl((S)-1-((S)-1-phenylethyl)aziridin-2-yl)methanol

烷基锌不对称烷基化手性氮丙啶配体的合成：二苯基((S)-1-((S)-1-苯乙基)氮丙啶-2-基)甲醇

• DOI: 10.15227/orgsyn.098.0446
• 发表时间: 2021-01
• 期刊: Organic Syntheses
• 影响因子: 0.7
• 作者: Sun; Siyuan
• 通讯作者: Siyuan