nickel catalyzed cross-couplings of amino acid derivatives ... · nickel catalyzed cross-couplings...
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Nickel Catalyzed Cross-Couplings of Amino Acid Derivatives via C-N Bond Activation
Earl Bampo
M. Watson Group
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MPW Research: Cross Couplings of Amine and Alcohol-derived
Electrophiles
1
Our research is focused on the development of Transition Metal catalyzed
cross-coupling reactions to form Carbon-Carbon bonds from Carbon-Nitrogen
and Carbon-Oxygen derived electrophiles.
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Prior Art: Known Cross-Coupling Reactions via C-N Activation
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• Limitations in previous
examples of C-N bond
activation in cross-
coupling reactions
• Previous work on Csp3-
N bond cleavage rely
on either electronic or
strain activation
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Prior Art: Pyridinium Formation
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• To enable cross coupling of
unactivated alkyl amines, our
group developed methods
demonstrating pyridinium salts
as great electrophiles for Nickel
Catalyzed Suzuki reactions.
• First example of cross-coupling
via C-N bond cleavage of alkyl
amines with unactivated alkyl
groups.
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This Work
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Why are these products interesting?• Products
structurally
similar to
known
Bioactive
molecules
(NSAIDs)
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Metal Free 𝛂-aryl ester formation
Wang
Wu, G.; Deng, Y.; Wu, C.; Zhang, Y.; Wang, J. Angew. Chem. Int. Ed. 2014, 53, 10510
Klauck, F. J. R.; James, M. J.; Glorius, F. Angew. Chem. Int. Ed. 2017, 56, 12336
Glorius
Light Mediated 𝛂-Aryl Ester Formation
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Substrate Synthesis
6
• Methyl Esters made in high yields
• Pyridinium formation with one by-product
• Pyridinium salts purified by column
chromatography
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Pyridinium Salts
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Pyridinium Salts
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Limitations in Substrate Synthesis
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Reaction Scope
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Reaction Scope
11
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Summary
• Variety of amino acids and aryl boroxines to form 𝛂-aryl
amino acid esters in moderate to high yields
• Air stable nickel source
• Readily available ligand
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Acknowledgements
MPW group:
Post Docs:
Dr. Sarah Pound
Dr. Shane Plunkett
Grad Students:
Corey Basch
Jennie Liao
Javon Rabb-Lynch
Megan Hoerrhner
Weiye Guan
Jianyu Xu
Kristen Baker
Undergrads:
Alana Duke
Winnie Cheung
University of Delaware Research Foundation
R01GM111820-01
COBREP20GM104316COBREP20GM103541
13
Zondlo Lab