Because a wide array of nitrogen-containing compounds exhibit bioactivity, the development of new methods for the formation of C?N bonds is a central challenge in synthetic organic chemistry. The discovery of catalysts for organic reactions is often desirable, since they can offer advantages from the standpoints of efficiency/economy. This proposal is directed at the discovery of new methods for metal-catalyzed C?N bond formation. Through the use of photoinduced copper catalysis via a radical pathway, we plan to expand the scope of N- alkylations well beyond that provided by SN2 reactions. These coupling reactions are anticipated to proceed under unusually mild conditions, to have broad applicability for the generation of diverse families of nitrogen- containing compounds, and to proceed with good stereoselectivity (when applicable). The research plan also describes mechanistic studies (e.g., isotopic labeling, stereochemical, mass spectrometry, and electron paramagnetic resonance spectroscopy) that will provide insight into the novel reaction pathways of these photoinduced, copper-catalyzed C?N bond-forming reactions. These mechanistic investigations will play an important role in facilitating our reaction-development program, as well as broadening our understanding of fundamental chemical reactivity.

Public Health Relevance

/RELEVANCE The development of efficient new chemical processes has an impact on a wide array of disciplines that require the synthesis of organic compounds (e.g., biological chemistry, pharmaceutical chemistry, and biology). Nitrogen-containing compounds have a high propensity to be bioactive (e.g., AbilifyTM, CrestorTM, CymbaltaTM, LipitorTM, and PlavixTM); consequently, the discovery of novel approaches to the synthesis of nitrogen-containing compounds, as well as enhancing the understanding of the underlying mechanisms of such processes, is an important endeavor for the biomedical community.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM109194-06
Application #
9729823
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Lees, Robert G
Project Start
2014-05-15
Project End
2022-05-31
Budget Start
2019-06-01
Budget End
2020-05-31
Support Year
6
Fiscal Year
2019
Total Cost
Indirect Cost
Name
California Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
009584210
City
Pasadena
State
CA
Country
United States
Zip Code
91125
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Ahn, Jun Myun; Peters, Jonas C; Fu, Gregory C (2017) Design of a Photoredox Catalyst that Enables the Direct Synthesis of Carbamate-Protected Primary Amines via Photoinduced, Copper-Catalyzed N-Alkylation Reactions of Unactivated Secondary Halides. J Am Chem Soc 139:18101-18106
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