Research ArticleORGANIC CHEMISTRY

A Rh(II)-catalyzed multicomponent reaction by trapping an α-amino enol intermediate in a traditional two-component reaction pathway

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Science Advances  08 Mar 2017:
Vol. 3, no. 3, e1602467
DOI: 10.1126/sciadv.1602467
  • Fig. 1 Designed strategy for the discovery of MCRs.

    The rational design of a general strategy based on the trapping of the active intermediates in traditional two-component reactions for the discovery of MCRs. (A) Gibbs free energy profiles for two-component reactions and MCR. (B) Strategy for discovering MCR.

  • Scheme 1 Proposed literature mechanism.

    Proposed mechanism of the formation of ketones from triazoles via α-amino enol D according to Miura et al. (52).

  • Scheme 2 Designed MCR pathway.

    Designed and observed transformation processes of trapping of the α-amino enol D with indole vinylimine ion E (A and C) versus competitive Davies’ cycloaddition pathway (B).

  • Scheme 3 Synthetic application of the products.

    The synthetic application of the multicomponent products for the rapid construction of 3-(methylsulfonyl)oxazolidin-2-one derivatives. d.r., diastereomeric ratio; DCM, dichloromethane.

  • Scheme 4 Control experiments.

    Control experiments to obtain an insight into the MCR pathway: (A and B) The results indicate that water is involved in the MCR; (C) the result indicates that Rh2(OAc)4 rather than heating promoted the reaction; and (D) the results exclude the other possible pathway according to which paraformaldehyde would first react with triazole.

  • Fig. 2 DFT investigation of the MCR.

    Calculated free energy profiles at 140°C in chlorobenzene for the generation and transformation of enol D into ketones and into the multicomponent product with vinylimine intermediate E. All the energy values are expressed in kilocalorie per mole.

  • Fig. 3 DFT investigation of the imine-enamine tautomerization.

    Calculated free energy profiles for the imine-enamine tautomerization from intermediate C to enol D. The blue line denotes the pathway via the transition state TS6 through one water molecule, whereas the red curve denotes the pathway via TS7 through two water molecules, respectively.

  • Scheme 5 Selective nucleophilic attack of the intermediate.

    Different nucleophilic attack selectivity of α-amino enol D versus Breslow intermediate.

  • Scheme 6 Plausible MCR mechanism.

    Proposed MCR mechanism of the α-amino enol D trapping by indole vinylimine ion E.

Supplementary Materials

  • Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/3/3/e1602467/DC1

    fig. S1. Rate-determining step of the proton transfer process compared with the active intermediate generation step in the reaction coordinate of the X–H (X = O, N) insertion product formation.

    fig. S2. Single-crystal x-ray structure determination of compound 6i (CCDC no. 1407544).

    fig. S3. Two-dimensional 1H-1H NOESY spectrum of compound 12.

    fig. S4. LC-MS spectra of the reaction solution containing indole, triazole, paraformaldehyde, H2O18, and Rh2(OAc)4.

    fig. S5. LC-MS spectra of the reaction solution containing indole, triazole, paraformaldehyde, and Rh2(OAc)4.

    fig. S6. Calculated free energy profiles of the formation of vinylimine ion E at 140°C in chlorobenzene.

    table S1. Reaction condition screening.

    data file S1. Characterization of products.

    data file S2. X-ray crystal data.

    data file S3. NMR spectra of compounds.

    data file S4. DFT calculation data.

  • Supplementary Materials

    This PDF file includes:

    • fig. S1. Rate-determining step of the proton transfer process compared with the active intermediate generation step in the reaction coordinate of the X–H (X = O, N) insertion product formation.
    • fig. S2. Single-crystal x-ray structure determination of compound 6i (CCDC no. 1407544).
    • fig. S3. Two-dimensional 1H-1H NOESY spectrum of compound 12.
    • fig. S4. LC-MS spectra of the reaction solution containing indole, triazole, paraformaldehyde, H2O18, and Rh2(OAc)4.
    • fig. S5. LC-MS spectra of the reaction solution containing indole, triazole, paraformaldehyde, and Rh2(OAc)4.
    • fig. S6. Calculated free energy profiles of the formation of vinylimine ion E at 140°C in chlorobenzene.
    • table S1. Reaction condition screening.
    • Legends for data file S1 to S4

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    Other Supplementary Material for this manuscript includes the following:

    • data file S1. Characterization of products.
    • data file S2. X-ray crystal data.
    • data file S3. NMR spectra of compounds.
    • data file S4. DFT calculation data.

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    Files in this Data Supplement:

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