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Copper-catalyzed aerobic oxidative coupling: From ketone and diamine to pyrazine

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Science Advances  09 Oct 2015:
Vol. 1, no. 9, e1500656
DOI: 10.1126/sciadv.1500656
  • Scheme 1 Traditional and theoretical pathways for the synthesis of pyrazines.
  • Scheme 2 The proposed strategy for oxidative coupling reactions between simple ketones and nucleophiles.
  • Fig. 1 Density functional theory (DFT) calculations for energy comparisons.

    (A to C) Free energy profile for the intramolecular cyclization process (A and B), and the corresponding electrostatic potential (ESP) maps (C).

  • Fig. 2 The capture experiment of hydroxyl radical.

    (A and B) The EPR spectra (X band, 9.4 GHz, room temperature) of (A) the reaction mixture of 1a and 2a under standard conditions and (B) the reaction mixture of 1a and 2a with the addition of DMPO under standard conditions.

  • Fig. 3 Copper K-edge spectrum (black line, 0.6 mmol of CuI in 12 ml of DMA; red line, 0.6 mmol of CuI and 12 mmol of LiCl in 12 ml of DMA).
  • Fig. 4 XANES spectra [red line, 0.6 mmol of CuI and 12 mmol of LiCl in 12 ml of DMA at room temperature (rt) under N2 for 5 min; black line, 0.6 mmol of CuI and 12 mmol of LiCl in 12 ml of DMA at rt under air for 5 min; brown line, 0.6 mmol of CuI, 12 mmol of LiCl, and 30 mmol of 2a in 12 ml of DMA at rt under air for 5 min; green line, 0.6 mmol of CuI, 12 mmol of LiCl, and 30 mmol of 2a in 12 ml of DMA at 120°C under air for 5 min].
  • Scheme 3 Reactivity of the Cu(II) species in the oxidative C–H/N–H coupling reaction.
  • Fig. 5 The mixture of CuI, LiCl, 2a, and DMA in the presence of air at 120°C for 5 min [green line, FT (Fourier transform) = 2.62 to 9.42 Å−1] and simulation (black line, fitting range = 1.09 to 1.84 Å).

    CN, coordination number, d, bond distance.

  • Fig. 6 Density functional theory (DFT) calculations for intramolecular cyclization of the enamine cationic radical.

    (A) Free energy profile for copper(II)-involved cyclization. (B) ESP map of complex IX. (C) Spin density map of complex IX. The numbers in parentheses are the corresponding Mulliken spin density located on each atom.

  • Scheme 4 Putative mechanism.

Supplementary Materials

  • Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/1/9/e1500656/DC1

    General information

    General procedure

    Table S1. The evaluation of several metal salts.

    Table S2. The effects of other solvents.

    Table S3. The effects of reaction temperature.

    Table S4. The effects of the ratio of substrates.

    Table S5. The effects of LiCl loading.

    Table S6. Oxidative C–H/N–H coupling between ketone and ethylenediamine under standard reaction conditions.

    Scheme S1. Gas chromatography–mass spectrometry analysis of the reaction between 1a and 2a.

    Scheme S2. Gas chromatography–mass spectrometry analysis of the reaction between 1a and 2e.

    EPR experiments

    Radical trapping experiments

    Scheme S3. Radical trapping experiment using BHT [2,6-bis(1,1-dimethylethyl)-4-methylphenol] as the scavenger.

    Scheme S4. Radical trapping experiment using TEMPO (2,2,6,6-tetramethylpiperidinyloxy) as the scavenger.

    XAS experiments

    General computational calculation details

    Detailed descriptions for products

    NMR data

    References (6573)

  • Supplementary Materials

    This PDF file includes:

    • General information
    • General procedure
    • Table S1. The evaluation of several metal salts.
    • Table S2. The effects of other solvents.
    • Table S3. The effects of reaction temperature.
    • Table S4. The effects of the ratio of substrates.
    • Table S5. The effects of LiCl loading.
    • Table S6. Oxidative C–H/N–H coupling between ketone and ethylenediamine under standard reaction conditions.
    • Scheme S1. Gas chromatography–mass spectrometry analysis of the reaction between 1a and 2a.
    • Scheme S2. Gas chromatography–mass spectrometry analysis of the reaction between 1a and 2e.
    • EPR experiments
    • Radical trapping experiments
    • Scheme S3. Radical trapping experiment using BHT 2,6-bis(1,1-dimethylethyl)-4-methylphenol as the scavenger.
    • Scheme S4. Radical trapping experiment using TEMPO (2,2,6,6-tetramethylpiperidinyloxy) as the scavenger.
    • XAS experiments
    • General computational calculation details
    • Detailed descriptions for products
    • NMR data
    • References (65–73)

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