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Recent advances in theoretical studies on transition-metal–catalyzed regioselective C-H functionalization of indoles

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Abstract

Indole compounds are widely found in natural products and drug candidates. The transition-metal–catalyzed regioselective C-H bond functionalization of indoles as the most efficient method for the synthesis of various functionalized indoles has been extensively studied in the past two decades due to its advantages of step economy and atom economy. In general, the catalysts included the transition-metals (Pd, Rh, Ru, Cu, Co, Fe, Zn, and Ga) and these reactions were accomplished with a remarkably wide range of coupling reagents for construction of various C–C and C-X (X = N, O, S) bonds. However, the general and important rules of the regioselectivity are not clear to date. Therefore, a comprehensive analysis through previous reported theoretical studies on transition-metal–catalyzed regioselective C-H bond functionalization of indoles was crucial and significant. In this review, we found that when the C-H bond activation process was the rate-determining step, the regioselectivity ordinarily occurred at the C7 or C4 positions (on benzene ring), and otherwise, the regioselectivity often occurred at C2 position (on pyrrole ring). For indoline substrates, the C-H bond functionalization occurred at the benzene ring.

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General rules of the regioselectivities for transition-metal-catalyzed C-H bond functionalization of indoles. This review collects major advances in the transition-metal-catalyzed C-H bond functionalization of indoles and indolines

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Funding

This work was supported by the Bioinformatics Center of Nanjing Agricultural University.

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Authors and Affiliations

  1. Jiangsu Key Laboratory of Pesticide Science and Department of Chemistry, College of Sciences, Nanjing Agricultural University, Nanjing, 210095, People’s Republic of China

    Hongsheng Ma, Tongyan Yu, Longxiao Chi, Cong Huang, Xuwen Li, Rui Zhang & Chao Deng

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  1. Hongsheng Ma
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  2. Tongyan Yu
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  3. Longxiao Chi
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  4. Cong Huang
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  5. Xuwen Li
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  7. Chao Deng
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Contributions

H. Ma: writing original draft; T. Yu, L. Chi: literature collection; C. Huang, X. Li: literature analysis and investigation; R. Zhang: manuscript revision; C. Deng: writing and supervision.

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Correspondence to Chao Deng.

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Ma, H., Yu, T., Chi, L. et al. Recent advances in theoretical studies on transition-metal–catalyzed regioselective C-H functionalization of indoles. J Mol Model 28, 267 (2022). https://doi.org/10.1007/s00894-022-05265-x

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