CAREER: Cross-Coupling via Amide Bond Cleavage: Development of Novel Synthetic Catalytic Methodology

职业：通过酰胺键断裂进行交叉偶联：新型合成催化方法的开发

• 批准号: 1650766
• 负责人: Michal Szostak
• 金额: $ 70万
• 依托单位: Rutgers University Newark
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1650766&HistoricalAwards=false
• 关键词: CAREER; Cross; Coupling; via; Amide

Amides are one of the most important groups in organic chemistry. Also known as a peptide bond, the amide bond is the key chemical group in proteins. Amides are extensively used in the synthesis of pharmaceuticals, polymers, and other useful materials. Development of new methods for the selective manipulation of amide bonds by transition metal catalysis is rare, in most part due to the high strength of the amide bonds. Currently, researchers have not yet discovered how to selectively control the chemical reactions of amides, nor have they developed general rules to guide these reactions to useful end-products. In this project, Dr. Szostak is developing a better understanding of how to control amide bond reactivity, and, in turn, how to achieve high levels of selectivity in catalytic reactions of amides. These catalytic reactions are critical for the synthesis of sophisticated and more complex molecules, and may result in new methods for the synthesis of better pharmaceuticals, modified peptides and polymers, and other useful materials. Dr. Szostak is involved in educational and outreach activities that are based on amide bond chemistry and reactions. These activities encompass high school student summer research program, and the development of new course modules to increase student exposure to the role of organic chemistry in modern society and to broaden their participation in research. With funding from the Chemical Catalysis Program of the Chemistry Division, Dr. Szostak of Rutgers University, Newark is developing new catalytic methods for the functionalization of amide bonds by direct metal insertion into the N-C amide bond. The research involves the development of new cross-coupling methods involving acyl- and aryl-metal intermediates. This research also focuses on the development of new methods of amide bond cross-coupling by cooperative catalysis. Amides serve as bench-stable, readily available cross-coupling partners to afford complex products by C-C bond forming reactions. The major challenge in the catalytic activation of amides is the amide bond conjugation. The project aims to provide the necessary knowledge for elucidating the factors controlling amide bond reactivity by N-C bond cleavage at the fundamental level. The project allows the development of a reactivity scale of amide bonds, the extensive characterization of distorted, non-planar amides, and the investigation of catalytic performance to aid the rational design of amide cross-coupling partners. The award is supporting educational and outreach activities led by Dr. Szostak. These activities focus on high school student summer research program, and the development of new course modules. The project provides opportunities for the students to stimulate their interest in STEM fields and encourages their broader participation in science.

酰胺是有机化学中最重要的基团之一。酰胺键也被称为肽键，是蛋白质中的关键化学基团。酰胺广泛用于药物、聚合物和其他有用材料的合成。通过过渡金属催化选择性操纵酰胺键的新方法的开发是罕见的，在很大程度上是由于酰胺键的高强度。目前，研究人员还没有发现如何选择性地控制酰胺的化学反应，也没有制定出指导这些反应生成有用的最终产物的一般规则。在这个项目中，Szostak博士正在更好地了解如何控制酰胺键的反应性，以及如何在酰胺的催化反应中实现高水平的选择性。这些催化反应对于复杂和更复杂的分子的合成至关重要，并且可能导致用于合成更好的药物、修饰的肽和聚合物以及其他有用材料的新方法。Szostak博士参与了基于酰胺键化学和反应的教育和推广活动。这些活动包括高中学生暑期研究计划，以及新课程模块的开发，以增加学生接触有机化学在现代社会中的作用，并扩大他们在研究中的参与。在罗格斯大学化学系化学催化计划的资助下，纽瓦克的Szostak博士正在开发新的催化方法，通过将金属直接插入N-C酰胺键来官能化酰胺键。该研究涉及新的交叉偶联方法的发展，涉及酰基和芳基金属中间体。本研究还着重于通过协同催化发展酰胺键交叉偶联的新方法。酰胺作为工作台稳定的，容易获得的交叉偶联配偶体，通过C-C键形成反应提供复杂的产物。酰胺催化活化的主要挑战是酰胺键的共轭。该项目的目的是提供必要的知识阐明的因素控制酰胺键的反应性的N-C键断裂在基础水平上。该项目允许开发酰胺键的反应性规模，扭曲的非平面酰胺的广泛表征，以及催化性能的研究，以帮助酰胺交叉偶联合作伙伴的合理设计。该奖项支持由Szostak博士领导的教育和外联活动。这些活动集中于高中学生暑期研究计划，以及新课程模块的开发。该项目为学生提供机会，激发他们对STEM领域的兴趣，并鼓励他们更广泛地参与科学。

项目成果

Recent Advances in Metal‐Catalyzed Functionalization of Indoles

金属催化吲哚功能化的最新进展

• DOI: 10.1002/adsc.202100116
• 发表时间: 2021
• 期刊: Advanced Synthesis & Catalysis
• 影响因子: 5.4
• 作者: Urbina, Kelvin;Tresp, David;Sipps, Karli;Szostak, Michal
• 通讯作者: Szostak, Michal

Application of Indazolin-3-ylidenes in Catalysis: Steric Tuning of Nonclassical Formally Normal N -Heterocyclic Carbenes with Dual Electronic Character for Catalysis

吲唑啉-3-亚基在催化中的应用：具有双电子特征的非经典形式正构N-杂环卡宾的空间调节催化

• DOI: 10.1021/acs.organomet.2c00140
• 发表时间: 2022
• 期刊: Organometallics
• 影响因子: 2.8
• 作者: Zhang, Jin;Wang, Yue;Zhang, Yuting;Liu, Ting;Fang, Shuai;Wang, Ruihong;Ma, Yangmin;Fang, Ran;Szostak, Roman;Szostak, Michal
• 通讯作者: Szostak, Michal

Copper(I)–Thiazol-2-ylidenes: Highly Reactive N-Heterocyclic Carbenes for the Hydroboration of Terminal and Internal Alkynes. Ligand Development, Synthetic Utility, and Mechanistic Studies

Copper(I)-Thiazol-2-ylidenes：用于末端和内部炔烃的硼氢化反应的高反应性 N-杂环卡宾。

• DOI: 10.1021/acscatal.2c04668
• 发表时间: 2022
• 期刊: ACS Catalysis
• 影响因子: 12.9
• 作者: Zhang, Jin;Li, Xue;Li, Tao;Zhang, Gaopeng;Wan, Kerou;Ma, Yangmin;Fang, Ran;Szostak, Roman;Szostak, Michal
• 通讯作者: Szostak, Michal

Well-defined, air- and moisture-stable palladium–imidazo[1,5- a ]pyridin-3-ylidene complexes: a versatile catalyst platform for cross-coupling reactions by L-shaped NHC ligands

结构明确、空气和湿气稳定的钯-咪唑并[1,5-a]吡啶-3-亚基配合物：用于 L 形 NHC 配体交叉偶联反应的多功能催化剂平台

• DOI: 10.1039/d2cy01136k
• 发表时间: 2022
• 期刊: Catalysis Science & Technology
• 影响因子: 5
• 作者: Zhou, Tongliang;Gao, Pengcheng;Bisz, Elwira;Dziuk, Błażej;Lalancette, Roger;Szostak, Roman;Szostak, Michal
• 通讯作者: Szostak, Michal

Suzuki‐Miyaura Cross‐Coupling of Amides using Well‐Defined, Air‐Stable [(PR 3 ) 2 Pd(II)X 2 ] Precatalysts

• DOI: 10.1002/adsc.202000122
• 发表时间: 2020-04
• 期刊: Advanced Synthesis & Catalysis
• 影响因子: 5.4
• 作者: Siyue Ma;Tongliang Zhou;Guangchen Li;M. Szostak