This research program focuses on addressing gaps in chemical structure and reactivity through the power of catalysis. Inspired by metalloenzymes, my laboratory designs, studies, and invents innovative tools for chemical synthesis that overcome the need for chiral auxiliaries and stoichiometric activating agents. The cross-coupling methods proposed feature the use of common functional groups (e.g., aldehydes, amines, alkynes, and alkenes) and generate new carbon-carbon and carbon-nitrogen bond with excellent atom economy. A wide range of chiral motifs can be accessed by this approach and the insights gained will ultimately enhance our ability to control chemical reactivity and build chemical structures. In turn, this knowledge greatly augments our ability to discover new medicines for treating human diseases, as well as prepare these medicines on large scale. The program features many new directions supported by compelling preliminary data including cyclase-inspired catalysis, shuttle catalysis, and tandem catalysis. Besides the practical value, this program will provide fundamental insights into the use of various catalysts, including rhodium, ruthenium, cobalt, and nickel, for the activation and functionalization of carbon-hydrogen bonds?a long standing challenge in modern organic chemistry.

Public Health Relevance

Projective Narrative Organic molecules make up nearly everything around us, including our medicines, clothing, and fuels. By finding innovative tools for building molecular architecture, we facilitate the discovery of life-saving therapeutics, invention of useful materials, and search for alternative energies. This project will enhance our ability to discover new medicines and subsequently prepare these medicines on large-scale. Inspired by Nature's catalyst, we will develop ideal, environmentally friendly, and powerful way to transform simple blocks (aldehydes, alkenes, and alkynes) into a wide range of valuable motifs.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Unknown (R35)
Project #
1R35GM127071-01
Application #
9486269
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Lees, Robert G
Project Start
2018-05-01
Project End
2023-04-30
Budget Start
2018-05-01
Budget End
2019-04-30
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92617
Yang, Xiao-Hui; Dong, Vy M (2017) Rhodium-Catalyzed Hydrofunctionalization: Enantioselective Coupling of Indolines and 1,3-Dienes. J Am Chem Soc 139:1774-1777
Yang, Xiao-Hui; Lu, Alexander; Dong, Vy M (2017) Intermolecular Hydroamination of 1,3-Dienes To Generate Homoallylic Amines. J Am Chem Soc 139:14049-14052
Le, Diane N; Riedel, Jan; Kozlyuk, Natalia et al. (2017) Cyclizing Pentapeptides: Mechanism and Application of Dehydrophenylalanine as a Traceless Turn-Inducer. Org Lett 19:114-117
Wu, Xuesong; Riedel, Jan; Dong, Vy M (2017) Transforming Olefins into ?,?-Unsaturated Nitriles through Copper Catalysis. Angew Chem Int Ed Engl 56:11589-11593