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 organic chemistry. Furthermore, because the two mirror-image isomers (""""""""enantiomers"""""""") of a molecule generally have different biological activity due to the """"""""handedness"""""""" of the molecules of life (e.g., peptides, DNA, RNA, and carbohydrates), there is a need in the biomedical community to efficiently generate compounds in stereoisomerically pure form. Finally, the development of catalyzed reactions is desirable, since they often offer advantages from the standpoints of efficiency/economy. This proposal is directed at addressing all three of these challenges, specifically, the discovery of new methods for the catalytic and enantioselective synthesis of nitrogen-containing compounds. In particular, the research plan describes the development of the first photoinduced, copper-catalyzed methods for the construction of C-N bonds. The 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). Furthermore, the research plan describes mechanistic studies (e.g., stereochemical, mass spectrometry, fluorometry, and electron paramagnetic resonance spectroscopy) that will provide insight into the unusual reaction pathway of these photoinduced, copper-catalyzed C-N bond-forming reactions, which likely proceed through a radical intermediate.
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, NexiumTM, and PlavixTM);consequently, the discovery of novel approaches to the synthesis of nitrogen-containing compounds, which is the focus of this proposal, is an important endeavor for the biomedical community.
|Ahn, Jun Myun; Ratani, Tanvi S; Hannoun, Kareem I et al. (2017) Photoinduced, Copper-Catalyzed Alkylation of Amines: A Mechanistic Study of the Cross-Coupling of Carbazole with Alkyl Bromides. J Am Chem Soc 139:12716-12723|
|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|
|Zhao, Wei; Wurz, Ryan P; Peters, Jonas C et al. (2017) Photoinduced, Copper-Catalyzed Decarboxylative C-N Coupling to Generate Protected Amines: An Alternative to the Curtius Rearrangement. J Am Chem Soc 139:12153-12156|
|Matier, Carson D; Schwaben, Jonas; Peters, Jonas C et al. (2017) Copper-Catalyzed Alkylation of Aliphatic Amines Induced by Visible Light. J Am Chem Soc 139:17707-17710|
|Fu, Gregory C (2017) Transition-Metal Catalysis of Nucleophilic Substitution Reactions: A Radical Alternative to SN1 and SN2 Processes. ACS Cent Sci 3:692-700|
|Johnson, Miles W; Hannoun, Kareem I; Tan, Yichen et al. (2016) A mechanistic investigation of the photoinduced, copper-mediated cross-coupling of an aryl thiol with an aryl halide. Chem Sci 7:4091-4100|
|Kainz, Quirin M; Matier, Carson D; Bartoszewicz, Agnieszka et al. (2016) Asymmetric copper-catalyzed C-N cross-couplings induced by visible light. Science 351:681-4|
|Ratani, Tanvi S; Bachman, Shoshana; Fu, Gregory C et al. (2015) Photoinduced, Copper-Catalyzed Carbon-Carbon Bond Formation with Alkyl Electrophiles: Cyanation of Unactivated Secondary Alkyl Chlorides at Room Temperature. J Am Chem Soc 137:13902-7|