The architectural and functional group complexity of natural products often confers to them unique modes of biological activity and significant therapeutic value. Despite transformative advances in catalytic methods and strategies for constructing highly complex molecules, the practice of total synthesis still remains a laborious and time intensive pursuit. Consequently, such compounds are rarely sought or evaluated as potential therapeutics. Historically, the development of new synthetic methods has had a profound impact on the efficiency of complex molecule synthesis. New reaction classes that lead to fundamentally novel reactivity stand to promote the largest advances in this regard. As a guide, we can look towards Nature?s synthetic strategies that systematically employ C-H oxidation and complexity generating C-C bond forming reactions. This proposal seeks to establish allylic C-H bonds as a new functional group for widespread use in complex molecule synthesis. To achieve this goal we will exploit a highly versatile ?-allyPd intermediate, accessed through allylic C-H cleavage, and develop general strategies by which it can participate in diverse reaction types with consistently high selectivities. Collectively, we expect these Pd(II)-catalyzed allylic C-H functionalization reactions to become fundamental tools for streamlining the synthesis of important structural motifs found in natural products, bioactive compounds, and medicinal agents. Moreover, the general principles that emerge from this approach will be broadly applicable to the field of C-H activation.)

Public Health Relevance

The objective of this research is to discover and develop catalytic reactions that establish the allylic C- H bond as a new functional group for widespread use in the synthesis of structural motifs found in natural products, bioactive compounds, and medicinal agents.)

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM076153-07
Application #
8525402
Study Section
Special Emphasis Panel (ZRG1-BCMB-P (02))
Program Officer
Lees, Robert G
Project Start
2006-09-26
Project End
2016-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
7
Fiscal Year
2013
Total Cost
$281,259
Indirect Cost
$90,189
Name
University of Illinois Urbana-Champaign
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
Pattillo, Christopher C; Strambeanu, Iulia I; Calleja, Pilar et al. (2016) Aerobic Linear Allylic C-H Amination: Overcoming Benzoquinone Inhibition. J Am Chem Soc 138:1265-72
Ammann, Stephen E; Rice, Grant T; White, M Christina (2014) Terminal olefins to chromans, isochromans, and pyrans via allylic C-H oxidation. J Am Chem Soc 136:10834-7
Osberger, Thomas J; White, M Christina (2014) N-Boc amines to oxazolidinones via Pd(II)/bis-sulfoxide/Brønsted acid co-catalyzed allylic C-H oxidation. J Am Chem Soc 136:11176-81
Howell, Jennifer M; Liu, Wei; Young, Andrew J et al. (2014) General allylic C-H alkylation with tertiary nucleophiles. J Am Chem Soc 136:5750-4
Bigi, Marinus A; White, M Christina (2013) Terminal olefins to linear ýý,ýý-unsaturated ketones: Pd(II)/hypervalent iodine co-catalyzed Wacker oxidation-dehydrogenation. J Am Chem Soc 135:7831-4
Delcamp, Jared H; Gormisky, Paul E; White, M Christina (2013) Oxidative Heck vinylation for the synthesis of complex dienes and polyenes. J Am Chem Soc 135:8460-3
Strambeanu, Iulia I; White, M Christina (2013) Catalyst-controlled C-O versus C-N allylic functionalization of terminal olefins. J Am Chem Soc 135:12032-7
Covell, Dustin J; White, M Christina (2013) A C-H oxidation approach for streamlining synthesis of chiral polyoxygenated motifs. Tetrahedron 69:7771-7778
Jiang, Chao; Covell, Dustin J; Stepan, Antonia F et al. (2012) Sequential allylic C-H amination/vinylic C-H arylation: a strategy for unnatural amino acid synthesis from α-olefins. Org Lett 14:1386-9
Stang, Erik M; White, M Christina (2011) On the macrocyclization of the erythromycin core: preorganization is not required. Angew Chem Int Ed Engl 50:2094-7

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