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Iridium and B(C6F5)3 co-catalyzed chemoselective deoxygenative reduction of tertiary amides: application to the efficient synthesis and late-stage modification of pharmaceuticals

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Abstract

The Vaska’s complex—tris(pentafluorophenyl)borane combination was found to be a highly efficient cooperative catalysis system for the hydrosilylative reduction of tertiary amides to yield amines under mild conditions. The reaction shows high chemoselectivity, tolerating halide, phenolyl, alkenyl, nitro, nitrile, ester, azido, ketone, and enone functional groups. For unsubstituted cyclohexanone carboxamide, two variations were established to achieve either catalytic concomitant reduction of the two carbonyl groups or selective reduction of the amide carbonyl. The protocol was applied to the efficient synthesis and late-stage modification of several pharmaceuticals and derivatives. Importantly, we showed that by simply prolonging reaction time to 24–28 h, the reaction can reach an exceptionally high efficiency with turnover number (TON) up to 9.8×106 and turnover frequency (TOF) up to 408,333 at a quite low catalyst loading of 0.00001 mol% (S/C (Ir) = 10,000,000).

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (21931010). We acknowledge Dr. Lei-Tao Huan for checking the TON and TOF of the reduction of 1g by repeating the experiment. We thank Ms. Yan-Jiao Gao for technical assistance.

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Author notes

  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Chemistry, Fujian Provincial Key Laboratory of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China

    Feng Han, Guang-Sheng Lu, Dong-Ping Wu & Pei-Qiang Huang

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  1. Feng Han
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Correspondence to Pei-Qiang Huang.

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The supporting information is available online at chem.scichina.com and link.springer.com/journal/11426. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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11426_2022_1501_MOESM1_ESM.pdf

Iridium and B(C6F5)3 co-catalyzed chemoselective deoxygenative reduction of tertiary amides: application to the efficient synthesis and late-stage modification of pharmaceuticals

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Han, F., Lu, GS., Wu, DP. et al. Iridium and B(C6F5)3 co-catalyzed chemoselective deoxygenative reduction of tertiary amides: application to the efficient synthesis and late-stage modification of pharmaceuticals. Sci. China Chem. 66, 1094–1100 (2023). https://doi.org/10.1007/s11426-022-1501-y

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  • DOI: https://doi.org/10.1007/s11426-022-1501-y

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