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Synthesis and characterization of hexaarylbenzenes with five or six different substituents enabled by programmed synthesis

Abstract

Since its discovery in 1825, benzene has served as one of the most used and indispensable building blocks of chemical compounds, ranging from pharmaceuticals and agrochemicals to plastics and those used in organic electronic devices. Benzene has six hydrogen atoms that can each be replaced by different substituents, which means that the structural diversity of benzene derivatives is intrinsically extraordinary. The number of possible substituted benzenes from n different substituents is (2n + 2n2 + 4n3 + 3n4 + n6)/12. However, owing to a lack of general synthetic methods for making multisubstituted benzenes, this potentially huge structural diversity has not been fully exploited. Here, we describe a programmed synthesis of hexaarylbenzenes using C–H activation, cross-coupling and [4+2] cycloaddition reactions. The present method allows for the isolation and structure–property characterization of hexaarylbenzenes with distinctive aryl substituents at all positions for the first time. Moreover, the established protocol can be applied to the synthesis of tetraarylnaphthalenes and pentaarylpyridines.

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Figure 1: Programmed synthesis of multiply arylated π-systems.
Figure 2: Synthesis of tetraarylthiophenes 5. Reaction conditions.
Figure 3: Synthesis of HABs with five different aryl groups.
Figure 4: Synthesis, isolation and structural characterization of HABs with six different aryl groups.
Figure 5: Application to other multiply arylated aromatics.

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Acknowledgements

This work was supported by the ERATO programme from JST (K.I.), the Funding Program for Next Generation World-Leading Researchers from JSPS (220GR049 to K.I.), a Grant-in-Aid for Scientific Research on Innovative Areas ‘Molecular Activation Directed toward Straightforward Synthesis’ (25105720 to J.Y.) and KAKENHI (25708005 to J.Y.) from MEXT. The authors thank S. Hagihara, T. Yoshidomi, K. Muto and A. Miyazaki (Nagoya University) for discussions and critical comments. K. Kuwata (Nagoya University) is acknowledged for assistance with mass spectroscopy. ITbM is supported by the World Premier International Research Center (WPI) Initiative, Japan.

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K.I. and J.Y. conceived the concept and directed the project. S.S. conducted experiments. Y.S. conducted X-ray crystal structure analysis. K.I. and J.Y. prepared the manuscript with feedback from others.

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Correspondence to Kenichiro Itami or Junichiro Yamaguchi.

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Supplementary information

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Supplementary information (PDF 18860 kb)

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Crystallographic data for compound 9A (CIF 24 kb)

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Crystallographic data for compound 11a (CIF 33 kb)

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Crystallographic data for compound 13 (CIF 23 kb)

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Crystallographic data for compound 15 (CIF 28 kb)

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Crystallographic data for compound 17b (CIF 26 kb)

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Suzuki, S., Segawa, Y., Itami, K. et al. Synthesis and characterization of hexaarylbenzenes with five or six different substituents enabled by programmed synthesis. Nature Chem 7, 227–233 (2015). https://doi.org/10.1038/nchem.2174

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