The carbonyl group is a structural motif common in a diverse range of natural products and pharmaceutical agents used to treat human diseases. This project involves the systematic expansion of hydroacylation as an ideal and powerful strategy for making carbonyl-containing compounds, including both esters and ketones. This innovative approach will lead to step- and atom-economical, sustainable, and stereoselective methods that greatly bolster our ability to access molecules relevant to human health, including enantiopure heterocycles and polyketides. In addition, these studies will provide efficient ways to make building blocks that can be elaborated to bioactive structures. Besides the practical value, this project 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

Our ability to discover new medicines and subsequently prepare these medicines on large-scale relies on the availability of versatile and practical methods for building organic molecules. In this context, hydroacylation is an ideal, environmentally friendly, and powerful way to transform simple compounds (e.g., aldehydes) into a wide range of valuable building blocks and final targets. By both rationale design and experimental observation, this project will transform hydroacylation into a broadly useful tool for building molecular structures relevant to understanding biology and treating human disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM105938-02
Application #
8689122
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Lees, Robert G
Project Start
2013-07-01
Project End
2017-04-30
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
2
Fiscal Year
2014
Total Cost
$279,406
Indirect Cost
$89,406
Name
University of California Irvine
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
Chen, Qing-An; Kim, Daniel K; Dong, Vy M (2014) Regioselective hydroacylation of 1,3-dienes by cobalt catalysis. J Am Chem Soc 136:3772-5
Kou, Kevin G M; Le, Diane N; Dong, Vy M (2014) Rh(I)-catalyzed intermolecular hydroacylation: enantioselective cross-coupling of aldehydes and ketoamides. J Am Chem Soc 136:9471-6
Oldenhuis, Nathan J; Dong, Vy M; Guan, Zhibin (2014) From racemic alcohols to enantiopure amines: Ru-catalyzed diastereoselective amination. J Am Chem Soc 136:12548-51
Dornan, Peter K; Kou, Kevin G M; Houk, K N et al. (2014) Dynamic kinetic resolution of allylic sulfoxides by Rh-catalyzed hydrogenation: a combined theoretical and experimental mechanistic study. J Am Chem Soc 136:291-8
Murphy, Stephen K; Bruch, Achim; Dong, Vy M (2014) Substrate-directed hydroacylation: rhodium-catalyzed coupling of vinylphenols and nonchelating aldehydes. Angew Chem Int Ed Engl 53:2455-9