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

点击翻译按钮获取中文摘要

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.