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Unique physicochemical and catalytic properties dictated by the B3NO2 ring system

Nature Chemistry volume 9, pages 571–577 (2017)Cite this article

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Abstract

The expansion of molecular diversity beyond what nature can produce is a fundamental objective in chemical sciences. Despite the rich chemistry of boron-containing heterocycles, the 1,3-dioxa-5-aza-2,4,6-triborinane (DATB) ring system, which is characterized by a six-membered B3NO2 core, remains elusive. Here, we report the synthesis of m-terphenyl-templated DATB derivatives, displaying high stability and peculiar Lewis acidity arising from the three suitably arranged boron atoms. We identify a particular utility for DATB in the dehydrative amidation of carboxylic acids and amines, a reaction of high academic and industrial importance. The three boron sites are proposed to engage in substrate assembly, lowering the entropic cost of the transition state, in contrast with the operative mechanism of previously reported catalysts and amide coupling reagents. The distinct mechanistic pathway dictated by the DATB core will advance not only such amidations, but also other reactions driven by multisite activation.

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Figure 1: Chemical space for six-membered heterocycles composed of B, C, N and O atoms and the structure of DATBs.
Figure 2: Synthesis and properties of DATBs.
Figure 3: Utility of DATB derivatives in catalytic direct amidations inspired by a calculated structure, where all three B atoms are coordinated.
Figure 4: NMR study and plausible catalytic cycle for the catalytic direct amidations promoted by DATB.

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Acknowledgements

This work is dedicated to Prof. Stuart L. Schreiber on the occasion of his 60th birthday. This work was supported by a Grant-in-Aid for Young Scientists A (KAKENHI no. 25713002) from the JSPS. N.K. thanks the JSPS for financial support via KAKENHI grant no. JP16H01043 ‘Precisely Designed Catalysts with Customized Scaffolding’. H.N. is a JSPS research fellow. The authors thank T. Kimura for the X-ray crystallographic analysis of 1a, 8a and 9, and they would also like to thank R. Sawa, Y. Kubota and K. Iijima for technical assistance with the analysis of 11B NMR spectra.

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  1. Institute of Microbial Chemistry (Bikaken), Tokyo, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo, 141-0021, Japan

    Hidetoshi Noda, Makoto Furutachi, Yasuko Asada, Masakatsu Shibasaki & Naoya Kumagai

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  1. Hidetoshi Noda
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Contributions

H.N., M.S. and N.K. conceived and designed the experiments. H.N., M.F. and Y.A. performed the experiments and analysed the data. H.N. conducted the density functional theory calculations. H.N., M.S. and N.K. co-wrote the paper.

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Correspondence to Masakatsu Shibasaki or Naoya Kumagai.

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The Institute of Microbial Chemistry (BIKAKEN) has filed a patent application on DATB catalysts for general direct amide-forming reactions.

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Supplementary information (PDF 12634 kb)

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Crystallographic data for compound 1a. (CIF 350 kb)

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Structure factors file for compound 8a. (CIF 587 kb)

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Crystallographic data for compound 9. (CIF 843 kb)

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Noda, H., Furutachi, M., Asada, Y. et al. Unique physicochemical and catalytic properties dictated by the B3NO2 ring system. Nature Chem 9, 571–577 (2017). https://doi.org/10.1038/nchem.2708

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