For the first time, researchers in Japan have installed multiple aryl groups onto a cubane framework. Cubane’s (C8H8) eight sp3-hybridised carbon atoms make it a rigid and unique molecule. Its derivatives are highly sought-after, but often limited to substitution at the 1- and 4-positions thanks to the commercially-available 1,4-cubanedicarboxylic acid precursor. Late-stage C–H transformations of cubane have been explored before, but it has only previously been possible to install halogen, carboxylic acid, phenyl and hydroxyl groups.

Starting from 1,4-diamidocubane, the team, led by Akiko Yagi and Kenichiro Itami of Nagoya University, first synthesised the monoarylated cubane by directed ortho C–H metalation followed by palladium-catalysed arylation. When they repeated these two steps with the product, however, the diarylcubane did not materialise. But by changing one of the amido groups to a cyano group, the acidity of the cubane was enhanced – and this meant it was possible for them to make the diarylcubane by directed ortho C–H metalation/arylation.

An image showing the programmable synthesis of diverse multiply arylated cubanes

Source: © Kenichiro Itami/Nagoya University

This reaction allows the late-stage and regioselective installation of a wide range of aryl groups, realising the first programmable synthesis of diverse multiply arylated cubanes

This second arylation was regioselective, and took place at the C–H bonds near the amido group. They proceeded to synthesise the tri- and tetra-arylcubanes from the diarylcubane, using similar reaction steps to before.

The programmable, predictable method enabled the synthesis of a wide range of mono-, di-, tri- and tetra-arylated cubanes. Such families of chiral cubane derivatives give access to fresh areas of chemical space, and have the potential to feature in pharmaceuticals and functional materials.

References

This article is open access

R Okude et al, Chem. Sci., 2020, DOI: 10.1039/d0sc01909g

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