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From alkylarenes to anilines via site-directed carbon–carbon amination

Nature Chemistryvolume 11pages7177 (2019) | Download Citation

Abstract

Anilines are fundamental motifs in various chemical contexts, and are widely used in the industrial production of fine chemicals, polymers, agrochemicals and pharmaceuticals. A recent development for the synthesis of anilines uses the primary amination of C–H bonds in electron-rich arenes. However, there are limitations to this strategy: the amination of electron-deficient arenes remains a challenging task and the amination of electron-rich arenes has a limited control over regioselectivity—the formation of meta-aminated products is especially difficult. Here we report a site-directed C–C bond primary amination of simple and readily available alkylarenes or benzyl alcohols for the direct and efficient preparation of anilines. This chemistry involves a novel C–C bond transformation and offers a versatile protocol for the synthesis of substituted anilines. The use of O2 as an environmentally benign oxidant is demonstrated, and studies on model compounds suggest that this method may also be used for the depolymerization of lignin.

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Full experimental procedures and spectral data for all the new compounds as well as computational details are included in the Supplementary Information and are available from the corresponding authors on request.

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Change history

  • 08 November 2018

    The version of this Article originally published online did not include a caution statement relating to safety concerns over some of the reagents used. All versions of the Article now have the following text included at the start of the Methods section “Caution: Sodium azide (NaN3) is highly toxic and also a potential explosion hazard; it can also react with organohalides to form explosive organic azides. Under acidic conditions, sodium azide can form hydrazoic acid (HN3) which is highly toxic. Considering these hazards, appropriate safety precautions should be taken when undertaking the C–C amination reactions reported in this Article.” Furthermore, in Fig. 2a, in the reaction conditions on the first equation it should have read DDQ not DDG; this has also been amended.

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Acknowledgements

Financial support from the National Basic Research Program of China (973 Program) (no. 2015CB856600), the National Natural Science Foundation of China (nos 21632001 and 21772002) and Peking University Health Science Center (no. BMU20160541) are appreciated.

Author information

Affiliations

  1. State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China

    • Jianzhong Liu
    • , Xu Qiu
    • , Xiaoqiang Huang
    • , Xiao Luo
    • , Cheng Zhang
    • , Jialiang Wei
    • , Jun Pan
    • , Yujie Liang
    • , Yuchao Zhu
    • , Qixue Qin
    • , Song Song
    •  & Ning Jiao
  2. State Key Laboratory of Organometallic Chemistry, Chinese Academy of Sciences, Shanghai, China

    • Ning Jiao

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Contributions

J.L. and N.J. conceived and designed the experiments; J.L., X.Q. and C.Z. carried out most of experiments; J.L., X.Q., X.L., J.W., J.P. and N.J. analysed data; J.L., X.Q., X.H., J.W., J.P., Y.L., Y.Z., Q.Q., S.S. and N.J. participated in discussion and co-wrote the paper; N.J. directed the project.

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Ning Jiao.

Supplementary information

  1. Supplementary Information

    General information, optimization data, substrate synthesis, general procedures, synthetic application, mechanistic experiments, additional references and characterization data

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DOI

https://doi.org/10.1038/s41557-018-0156-y