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 #
1R01GM105938-01A1
Application #
8596746
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
2013-07-01
Budget End
2014-04-30
Support Year
1
Fiscal Year
2013
Total Cost
$279,506
Indirect Cost
$89,506
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
Park, Jung-Woo; Chen, Zhiwei; Dong, Vy M (2016) Rhodium-Catalyzed Enantioselective Cycloisomerization to Cyclohexenes Bearing Quaternary Carbon Centers. J Am Chem Soc 138:3310-3
Cruz, Faben A; Chen, Zhiwei; Kurtoic, Sarah I et al. (2016) Tandem Rh-catalysis: decarboxylative β-keto acid and alkyne cross-coupling. Chem Commun (Camb) 52:5836-9
Whittaker, Aaron M; Dong, Vy M (2015) Nickel-catalyzed dehydrogenative cross-coupling: direct transformation of aldehydes into esters and amides. Angew Chem Int Ed Engl 54:1312-5
Park, Jung-Woo; Kou, Kevin G M; Kim, Daniel K et al. (2015) Rh-Catalyzed Desymmetrization of α-Quaternary Centers by Isomerization-Hydroacylation. Chem Sci 6:4479-4483
Chen, Qing-An; Chen, Zhiwei; Dong, Vy M (2015) Rhodium-Catalyzed Enantioselective Hydroamination of Alkynes with Indolines. J Am Chem Soc 137:8392-5
Murphy, Stephen K; Park, Jung-Woo; Cruz, Faben A et al. (2015) Organic chemistry. Rh-catalyzed C-C bond cleavage by transfer hydroformylation. Science 347:56-60
Murphy, Stephen K; Bruch, Achim; Dong, Vy M (2015) Mechanistic insights into hydroacylation with non-chelating aldehydes†Electronic supplementary information (ESI) available: Materials and methods, reaction procedures, characterization data. CCDC 1012849. For ESI and crystallographic data in CIF or othe Chem Sci 6:174-180
Kou, Kevin G M; Longobardi, Lauren E; Dong, Vy M (2015) Rhodium(I)-Catalyzed Intermolecular Hydroacylation of α-Keto Amides and Isatins with Non-Chelating Aldehydes. Adv Synth Catal 357:2233-2237
Chen, Qing-An; Cruz, Faben A; Dong, Vy M (2015) Alkyne hydroacylation: switching regioselectivity by tandem ruthenium catalysis. J Am Chem Soc 137:3157-60
Kou, K G M; Dong, V M (2015) Tandem rhodium catalysis: exploiting sulfoxides for asymmetric transition-metal catalysis. Org Biomol Chem 13:5844-7

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