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Rhodium-catalysed asymmetric allylic arylation of racemic halides with arylboronic acids

Nature Chemistry volume 7, pages 935–939 (2015)Cite this article

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Abstract

C s p 2 − C s p 2 cross-coupling reactions between arylboronic acid and aryl halides are widely used in both academia and industry and are strategically important in the development of new agrochemicals and pharmaceuticals. C s p 2 − C s p 3 cross-coupling reactions have been developed, but enantioselective variations are rare and simply retaining the stereochemistry is a problem. Here we report a highly enantioselective C s p 2 − C s p 3 bond-forming method that couples arylboronic acids to racemic allyl chlorides. Both enantiomers of a cyclic chloride are converted into a single enantiomer of product via a dynamic kinetic asymmetric transformation. This Rh-catalysed method uses readily available and inexpensive building blocks and is mild and broadly applicable. For electron-deficient, electron-rich or ortho-substituted boronic acids better results are obtained with racemic allyl bromides. Oxygen substitution in the allyl halide is tolerated and the products can be functionalized to provide diverse building blocks. The approach fills a significant gap in the methods for catalytic asymmetric synthesis.

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Figure 1: C–C bond-forming reactions, including this work.
Figure 2: Scale up and downstream reactivity of coupling products.

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Acknowledgements

We acknowledge financial support from the Engineering and Physical Sciences Research Council (EP/H003711/1, a Career Acceleration Fellowship to S.F.).

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  1. Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK

    Mireia Sidera & Stephen P. Fletcher

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  1. Mireia Sidera
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Contributions

M.S. performed the experiments and S.F. guided the research. Both authors contributed to designing the experiments, analysing the data and writing the manuscript.

Corresponding author

Correspondence to Stephen P. Fletcher.

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Competing interests

The authors are named as inventors on a UK patent application filed by Isis Innovation, which is the technology transfer arm of the University of Oxford.

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Sidera, M., Fletcher, S. Rhodium-catalysed asymmetric allylic arylation of racemic halides with arylboronic acids. Nature Chem 7, 935–939 (2015). https://doi.org/10.1038/nchem.2360

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