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

酰胺类化合物是有机化学中最重要的基团之一。也被称为肽键，酰胺键是蛋白质中的关键化学基团。酰胺被广泛用于合成药物、聚合物和其他有用的材料。通过过渡金属催化选择性操纵酰胺键的新方法的开发很少，主要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，也没有制定出一般规则来指导这些反应生成有用的最终产品。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，进而了解如何在酰胺的催化反应中实现高水平的选择性。这些催化反应对于合成复杂和复杂的分子是至关重要的，并可能导致合成更好的药物、改性肽和聚合物以及其他有用材料的新方法。Szostak博士参与了以酰胺键化学和反应为基础的教育和推广活动。这些活动包括高中生暑期研究计划，以及开发新的课程模块，以增加学生对有机化学在现代社会中的作用的接触，并扩大他们参与研究的范围。在化学系化学催化项目的资助下，罗格斯大学的Szostak博士正在开发通过将金属直接插入N-C酰胺键来实现酰胺键功能化的新催化方法。这项研究涉及开发涉及酰基和芳基金属中间体的新的交叉偶联方法。本研究还重点开发了利用协同催化进行酰胺键交叉偶联的新方法。酰胺作为稳定的、容易获得的交叉偶联伙伴，通过C-C键的形成反应提供复杂的产品。酰胺类化合物催化活化的主要挑战是酰胺键的共轭。该项目旨在为阐明在基础水平上通过N-C键断裂来控制酰胺键反应的因素提供必要的知识。该项目允许开发酰胺键的反应性标度，对扭曲的非平面酰胺进行广泛的表征，并对催化性能进行研究，以帮助合理设计酰胺交叉偶联伙伴。该奖项用于支持绍斯塔克博士领导的教育和外展活动。这些活动的重点是高中生暑期研究计划，以及新课程模块的开发。该项目为学生提供了激发他们对STEM领域的兴趣的机会，并鼓励他们更广泛地参与科学。

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.