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Spatial and temporal control of the alkyne–azide cycloaddition by photoinitiated Cu(II) reduction

Nature Chemistry volume 3, pages 256259 (2011) | Download Citation

Abstract

The click reaction paradigm is focused on the development and implementation of reactions that are simple to perform while being robust and providing exquisite control of the reaction and its products. Arguably the most prolific and powerful of these reactions, the copper-catalysed alkyne–azide reaction (CuAAC) is highly efficient and ubiquitous in an ever increasing number of synthetic methodologies and applications, including bioconjugation, labelling, surface functionalization, dendrimer synthesis, polymer synthesis and polymer modification. Unfortunately, as the Cu(I) catalyst is typically generated by the chemical reduction of Cu(II) to Cu(I), or added as a Cu(I) salt, temporal and spatial control of the CuAAC reaction is not readily achieved. Here, we demonstrate catalysis of the CuAAC reaction via the photochemical reduction of Cu(II) to Cu(I), affording comprehensive spatial and temporal control of the CuAAC reaction using standard photolithographic techniques. Results reveal the diverse capability of this technique in small molecule synthesis, patterned material fabrication and patterned chemical modification.

  • Compound C6H10

    1-Hexyne

  • Compound C4H7N3O2

    Ethyl 2-azidoacetate

  • Compound C26H27O3P

    (Phenylphosphoryl)bis(mesitylmethanone)

  • Compound C12H16O4

    2-Hydroxy-1-(4-(2-hydroxyethoxy)phenyl)-2-methylpropan-1-one

  • Compound C10H17N3O2

    Ethyl 2-(4-butyl-1H-1,2,3-triazol-1-yl)acetate

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Acknowledgements

The authors acknowledge financial support from the US Department of Education's Graduate Assistantship in Areas of National Need (B.J.A., C.A.D.), Sandia National Labs (B.J.A.) and the National Science Foundation (grant CBET 0933828, C.J.K.).

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Affiliations

  1. Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado 80309-0424, USA

    • Brian J. Adzima
    • , Youhua Tao
    • , Christopher J. Kloxin
    • , Cole A. DeForest
    • , Kristi S. Anseth
    •  & Christopher N. Bowman
  2. Howard Hughes Medical Institute, University of Colorado, UCB Box 424 Boulder, Colorado 80309-0424, USA

    • Kristi S. Anseth

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Contributions

C.N.B., C.J.K. and B.J.A. developed the concept. B.J.A., Y.T., C.J.K., C.A.D., K.S.A. and C.N.B. designed the experiments. C.A.D. synthesized the materials used. B.J.A., Y.T. and C.A.D. performed the experiments. B.J.A., C.J.K., K.S.A. and C.N.B. composed the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Christopher N. Bowman.

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DOI

https://doi.org/10.1038/nchem.980