In this project funded by the Chemical Catalysis Program of the Chemistry Division, Professor Timothy H. Warren of Georgetown University will develop catalytic carbon-hydrogen (C-H) amination reactions as a means of preparing new carbon-nitrogen (C-N) bonds without the need to pre-functionalize the reactive sites. The ability to directly affect the C-H to C-N transformation without the need to isolate, purify, and transform corresponding precursors offers the appealing prospect of reduced cost, energy consumption and environmental impact. Building on previous results, this approach connects the chemical and electronic structures of copper and nickel nitrene and amide complexes to their catalytic reactivity. The work specifically examines copper and nickel nitrene complexes derived from organoazides, the amine and substrate scope of the reactions, and new catalysts architectures to further enhance the efficiency and scope of the catalytic reactions. The broader impacts of this project include national and international collaborations that will expand the student's perspective on the way science is conducted within the larger scientific community. Professor Warren is active in mentoring high school students, undergraduates (especially through the NSF-sponsored REU program) and graduate students.

This work will expand the repertoire of methods that can be used in the chemical synthesis of compounds containing C-N bonds. The results of these studies could have many important long term impacts on a variety of applications in synthetic and materials chemistry, particularly in medicinal or pharmaceutical products.

Project Report

Catalytic C-H amination is an attractive strategy to directly convert carbon-hydrogen (C-H) bonds to new carbon-nitrogen (C-N) bonds that are ubiquitous in organic molecules connected to life as well as advanced materials. This approach offers substantial opportunities to streamline chemical syntheses by decreasing the number of synthetic steps, taking advantage of normally unreactive carbon-hydrogen bonds present in essentially all organic molecules. C-H amination can simultaneously accelerate discovery and development in the chemical synthesis of molecules containing carbon-nitrogen bonds while minimizing the associated environmental footprint, especially with catalyst systems based on Earth abundant metals such as copper. Our work has addressed significant challenges involving the atom-economical incorporation of N atoms that bear desirable N-based functionalities in a single transformation at a C-H bond. Detailed studies involving isolable, yet highly reactive intermediates employing the easily accessible, commercially available copper catalyst [Cl2NN]Cu developed in our laboratory serve as a springboard to a family of synthetically useful copper-catalyzed C-H functionalization reactions. Key findings of this grant include (a) the identification of highly reactive copper intermediates capable of reacting under mild conditions with normally unreactive C-H bonds, (b) the development of new synthetic protocols that allow for coupling of C-H bonds with alkyl and aromatic amines to provide a strategy for C-N bond formation, and (c) the identification of a new carbon-oxygen (C-O) bond forming reaction that overcomes limitations present in the Williamson ether synthesis, a reaction taught to all college organic chemistry students. This grant has resulted in novel strategies to employ normally inert carbon-hydrogen bonds in organic synthesis and has produced new intellectual property. This project has provided several graduate, undergraduate, and high school students the opportunity to learn how to design new chemical reactions from first principles, employing a wide range of instrumentation that allows them to "see" their catalysts at work. Furthermore, a number of students from underrepresented groups have participated in this work as well as students very early in their scientific careers such as high school students; several appear as co-authors of published work. Students at Georgetown have been enriched through a couple of short term international visitors to Georgetown as well as through the opportunity to interact with collaborators both in the US and abroad. Professor Warren and students on this project have connected with high-risk middle school students from low income families via outreach activities with the organiziation Higher Achievement. Founded in Washington, DC in 1975, this organization hosts rigorous after-school and summer academic program to great success – 93% of the graduates go on to college. In each of two consecutive summers, Professor Warren and his students invited ca. 70-90 middle school scholars to Georgetown for a "Chemistry Show" sharing the fun and excitement of chemistry in the context of current events. Each event included visits by smaller groups to the Warren laboratory to see the tools of modern science, capped with liquid nitrogen ice cream for dessert.

Agency
National Science Foundation (NSF)
Institute
Division of Chemistry (CHE)
Type
Standard Grant (Standard)
Application #
1012523
Program Officer
Carol Bessel
Project Start
Project End
Budget Start
2010-09-15
Budget End
2014-08-31
Support Year
Fiscal Year
2010
Total Cost
$435,000
Indirect Cost
Name
Georgetown University
Department
Type
DUNS #
City
Washington
State
DC
Country
United States
Zip Code
20057