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

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Abstract

Multicomponent reactions (MCRs) represent an ideal organic synthesis tool for the rapid construction of complex molecules due to their step and atom economy. Compared to two-component reactions, the development of new MCRs has been greatly limited during the 170 years since the first MCR was reported. Theoretically, the trapping of an active intermediate generated from two components by a third component could change the traditional two-component reaction pathway, leading to the discovery of MCRs. We report an example of the trapping of α-imino enols generated in situ from 1-sulfonyl-1,2,3-triazoles via α-imino metal carbene species by vinylimine ions using C(2)-substituted indoles and paraformaldehyde as precursors in the presence of a rhodium(II) catalyst. The traditional enol-ketone transformation pathway was suspended by the trapping procedure and efficiently switched to an MCR pathway to produce α-amino-β-indole ketones in moderate to good yields. Unexpectedly, the resulting products and the theoretical density functional theory (DFT) calculation results indicated that the enolic carbon had a stronger nucleophilicity than the well-known traditional enamic carbon in the trapping process. The reaction mechanism was investigated using control experiments and detailed DFT calculations, and the synthetic application of the products was also illustrated. The developed strategy provides a mild and rapid access to α-amino-β-indole ketones and suggests a rationale for the discovery of MCRs by trapping an active intermediate with a third component in a traditional two-component reaction pathway.

Keywords
  • triazole
  • α-imino rhodium carbene
  • vinylimine intermediates
  • α-imino enol
  • multi-component reaction

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