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  • Nickel Catalyzed Cross-Couplings of Amino Acid Derivatives via C-N Bond Activation

    Earl Bampo

    M. Watson Group

  • 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.

  • Prior Art: Known Cross-Coupling Reactions via C-N Activation

    2

    • 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

  • Prior Art: Pyridinium Formation

    3

    • 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.

  • This Work

    4

    Why are these products interesting?• Products structurally

    similar to

    known

    Bioactive

    molecules

    (NSAIDs)

  • 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

    5

  • Substrate Synthesis

    6

    • Methyl Esters made in high yields

    • Pyridinium formation with one by-product

    • Pyridinium salts purified by column

    chromatography

  • Pyridinium Salts

    7

  • Pyridinium Salts

    8

  • Limitations in Substrate Synthesis

    9

  • Reaction Scope

    10

  • Reaction Scope

    11

  • 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

    12

  • 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

    R01 GM111820-01

    COBRE P20GM104316 COBRE P20GM103541

    13

    Zondlo Lab

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