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

作者：Liu, Shunying; Yao, Wenfeng; Liu, Yuan; Wei, Qinghua; Chen, Jianghui; Wu, Xiang; Xia, Fei^*; Hu, Wenhao^*

来源：Science Advances, 2017, 3(3): e1602467.

DOI：10.1126/sciadv.1602467

• Active intermediates
• Control experiments
• Multi-component reactions
• Multicomponent reactions (MCRs)
• Substituted indoles
• Synthetic application
• Theoretical density
• Transformation pathways

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 alpha-imino enols generated in situ from 1-sulfonyl-1,2,3-triazoles via alpha-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 alpha-amino-beta-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 alpha-amino-beta-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.

• 出版日期2017-3
• 单位华东师范大学