As exemplified by the Haber-Bosch reaction, which sustains half the human population, and enantioselective hydrogenation, which is the foremost chemical method used to create chiral pharmaceutical and agrochemical ingredients, catalytic hydrogenation has had a greater impact on how humans live and die than any other chemical process. Prior to our work, the sole example of a ?C-C bond forming hydrogenation? was hydroformylation, which is the largest application of homogenous metal catalysis. My laboratory has pioneered a broad, new class of C-C bond formations that merge the characteristics of catalytic hydrogenation and carbonyl addition ? processes in which two or more reactants are hydrogenated to form a single, more complex product. These transformations bypass the use of stoichiometric carbanions, offering a byproduct-free alternative to a range of classical carbonyl or imine additions. This concept is extended further by ?C-C bond forming transfer hydrogenations? that directly convert lower alcohols to higher alcohols, again in the absence of stoichiometric metals. In the proposed funding period, we will develop methods for the stereo- and site-selective formation of quaternary centers, the use of ?-olefins as couplings partners, and the use of base metal (Fe, Co) catalysts. Our goal is to develop environmentally benign methods for the conversion of inexpensive chemical feedstocks to value-added building blocks for use in the manufacture of pharmaceutical and agrochemical ingredients.

Public Health Relevance

C-C Bond formation is central to the endeavor of chemical synthesis. We have developed two new classes C-C bond formations: (a) reductive couplings induced via catalytic hydrogenation, and (b) H2-auto-transfer processes that directly convert lower alcohols to higher alcohols. Here, we propose to continue our investigations into the direct redox- triggered C-C coupling of alcohols with a focus on the development of stereo- and site-selective methods for construction of quaternary centers, the use of ?-olefins as couplings partners, and the use of base metal (Fe, Co) catalysts.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM069445-14
Application #
9415467
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Lees, Robert G
Project Start
2005-03-15
Project End
2021-03-31
Budget Start
2018-04-01
Budget End
2019-03-31
Support Year
14
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Texas Austin
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78759
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Wurm, Thomas; Turnbull, Ben W H; Ambler, Brett R et al. (2017) Thermal Hetero-Diels-Alder Reaction of Benzocyclobutenones with Isatins To Form 2-Oxindole Spirolactones. J Org Chem 82:13751-13755
Kim, Seung Wook; Lee, Wonchul; Krische, Michael J (2017) Asymmetric Allylation of Glycidols Mediated by Allyl Acetate via Iridium-Catalyzed Hydrogen Transfer. Org Lett 19:1252-1254
Luong, Tom; Chen, Shujie; Qu, Ke et al. (2017) Ruthenium(0)-Catalyzed C-C Coupling of Alkynes and 3-Hydroxy-2-oxindoles: Direct C-H Vinylation of Alcohols. Org Lett 19:966-968
Feng, Jiajie; Holmes, Michael; Krische, Michael J (2017) Acyclic Quaternary Carbon Stereocenters via Enantioselective Transition Metal Catalysis. Chem Rev 117:12564-12580

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