Research ArticleChemistry

Isolation of bis(copper) key intermediates in Cu-catalyzed azide-alkyne “click reaction”

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Science Advances  12 Jun 2015:
Vol. 1, no. 5, e1500304
DOI: 10.1126/sciadv.1500304
  • Fig. 1 Stepwise reproduction of the CuAAC reaction; isolation of mono- and bis(copper) intermediates involved in both catalytic pathways.

    (A) Stoichiometric reactions reproducing the different steps of the postulated CuAAC catalytic cycles, which allow for the isolation of a previously postulated π,σ-bis(copper) complex of type 1Cu2 and of the never-mentioned bis(copper) triazole 2Cu2. (B) Kinetic profiles of the stoichiometric reactions of 1Cua and 1Cu2a with benzyl azide, which reveal the critical rate acceleration when the bimetallic complex 1Cu2a is used. (C) Molecular view of complexes 1Cu2a (left, table S1), 2Cu2a (center, table S2), and 1Cu2b (right, table S3) in the solid state (for clarity, H atoms and anions are omitted).

  • Fig. 2 Kinetic profiles of the CuAAC reaction of phenyl acetylene with benzyl azide using CAAC-supported mono- and bis(copper) catalysts.

    (A) The kinetic profiles of the catalytic reaction of phenyl acetylene with benzyl azide demonstrate the superior catalytic activity of the dinuclear complexes 1Cu2a and 2Cu2a over their mononuclear counterparts 1Cua and 2Cua, and show that the (CAAC)CuOTf complex adopts the dinuclear pathway after an initiation period. (B) Evolution of the amount of dimetallated triazole 2Cu2a and free triazole 3 during the early period of the catalytic reaction using 1Cu2a as catalyst, showing that 2Cu2a is the resting state of the catalytic cycle. a.u., arbitrary units. (C) Same as (B), but of 2Cua and 3 using 1Cua as catalyst. (D and E) Et3N, as a proton scavenger, allows for the rapid formation of 1Cu2a from (CAAC)CuOTf and phenyl acetylene (D), and consequently shortens the induction period of the CuAAC reaction described in (A) using (CAAC)CuOTf (E).

  • Fig. 3 Mechanistic conclusions: Both the mono- and bis-copper pathways are active in the CuAAC reaction, but the latter is kinetically favored.

    The protodemetallation is performed by the alkyne, which regenerates the metallated acetylide, thereby excluding the σ-copper acetylide from the preferred catalytic cycle.

Supplementary Materials

  • Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/1/5/e1500304/DC1

    Supplementary text

    Fig. S1. 1H NMR of (CAAC)CuOAc in CD2Cl2.

    Fig. S2. 13C NMR of (CAAC)CuOAc in CD2Cl2.

    Fig. S3. 1H NMR of (CAAC)CuCl in CD2Cl2.

    Fig. S4. 13C NMR of (CAAC)CuCl in CD2Cl2.

    Fig. S5. 1H NMR of (CAAC)CuOTf in CDCl3.

    Fig. S6. 13C NMR of (CAAC)CuOTf in CDCl3.

    Fig. S7. 1H NMR of 1Cua in CD2Cl2.

    Fig. S8. 13C NMR of 1Cua in CD2Cl2.

    Fig. S9. 1H NMR of 1Cu2a in CD2Cl2.

    Fig. S10. 13C NMR of 1Cu2a in CD2Cl2.

    Fig. S11. 1H NMR of 2Cu2a in CD2Cl2.

    Fig. S12. 3C NMR of 2Cu2a in CD2Cl2.

    Fig. S13. 1H NMR of 1Cu2b in CD2Cl2.

    Fig. S14. 3C NMR of 1Cu2b in CD2Cl2.

    Fig. S15. 1H NMR of 2Cua in CD2Cl2.

    Fig. S16. 13C NMR of 2Cua in CD2Cl2.

    Fig. S17. Evolution of the annulation reaction monitored by 1H NMR.

    Fig. S18. Evolution of the protodemetallation reaction monitored by 1H NMR.

    Fig. S19. Evolution of the catalytic reaction between benzyl azide and phenyl acetylene monitored by 1H NMR.

    Table S1. Crystal data and structure refinement for 1Cu2a.

    Table S2. Crystal data and structure refinement for 2Cu2a (X = BF4).

    Table S3. Crystal data and structure refinement for 1Cu2b (X = BF4).

  • Supplementary Materials

    This PDF file includes:

    • Supplementary text
      Fig. S1. 1H NMR of (CAAC)CuOAc in CD2Cl2.
      Fig. S2. 13C NMR of (CAAC)CuOAc in CD2Cl2.
      Fig. S3. 1H NMR of (CAAC)CuCl in CD2Cl2.
      Fig. S4. 13C NMR of (CAAC)CuCl in CD2Cl2.
      Fig. S5. 1H NMR of (CAAC)CuOTf in CDCl3.
      Fig. S6. 13C NMR of (CAAC)CuOTf in CDCl3.
      Fig. S7. 1H NMR of 1Cua in CD2Cl2.
      Fig. S8. 13C NMR of 1Cua in CD2Cl2.
      Fig. S9. 1H NMR of 1Cu2a in CD2Cl2.
      Fig. S10. 13C NMR of 1Cu2a in CD2Cl2.
      Fig. S11. 1H NMR of 2Cu2a in CD2Cl2.
      Fig. S12. 3C NMR of 2Cu2a in CD2Cl2.
      Fig. S13. 1H NMR of 1Cu2b in CD2Cl2.
      Fig. S14. 3C NMR of 1Cu2b in CD2Cl2.
      Fig. S15. 1H NMR of 2Cua in CD2Cl2.
      Fig. S16. 13C NMR of 2Cua in CD2Cl2.
      Fig. S17. Evolution of the annulation reaction monitored by 1H NMR.
      Fig. S18. Evolution of the protodemetallation reaction monitored by 1H NMR.
      Fig. S19. Evolution of the catalytic reaction between benzyl azide and phenyl
      acetylene monitored by 1H NMR.
      Table S1. Crystal data and structure refinement for 1Cu2a.
      Table S2. Crystal data and structure refinement for 2Cu2a (X = BF4).
      Table S3. Crystal data and structure refinement for 1Cu2b (X = BF4).

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