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The direct anti-Markovnikov addition of mineral acids to styrenes

Nature Chemistry volume 6, pages 720–726 (2014)Cite this article

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Abstract

The direct anti-Markovnikov addition of strong Brønsted acids to alkenes remains an unsolved problem in synthetic chemistry. Here, we report an efficient organic photoredox catalyst system for the addition of HCl, HF and also phosphoric and sulfonic acids to alkenes, with complete regioselectivity. These transformations were developed using a photoredox catalyst in conjunction with a redox-active hydrogen atom donor. The nucleophile counterion plays a critical role by ensuring high reactivity, with 2,6-lutidinium salts typically furnishing the best results. The nature of the redox-active hydrogen atom donor is also consequential, with 4-methoxythiophenol providing the best reactivity when 2,6-lutidinium salts are used. A novel acridinium sensitizer provides enhanced reactivity within several of the more challenging reaction manifolds. This Article demonstrates how nucleophilic addition reactions mediated by photoredox catalysis can change the way electrophilic and homofugal precursors are constructed.

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Figure 1: Previous and current reports on the anti-Markovnikov addition of nucleophiles to alkenes.
Figure 2: Proposed catalytic cycle for the anti-Markovnikov hydrohalogenation of styrenyl alkenes.
Figure 3: Effect of different amine hydrochloride salts on the anti-Markovnikov hydrochlorination of β-methylstyrene.

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Acknowledgements

The authors acknowledge support from The David and Lucile Packard Foundation.

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Authors and Affiliations

  1. Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, 27599-3290, North Carolina, USA

    Dale J. Wilger, Jean-Marc M. Grandjean, Taylor R. Lammert & David A. Nicewicz

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  1. Dale J. Wilger
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  3. Taylor R. Lammert
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Contributions

D.J.W., J-M.M.G. and T.R.L. performed the experiments. D.A.N. guided the research. D.J.W. performed the experiments on the optimization and substrate scope for the anti-Markovnikov hydrochlorination. D.J.W. and J-M.M.G. performed the experiments on the optimization and substrate scope for the anti-Markovnikov hydrofluorination. D.J.W., J-M.M.G. and T.R.L. performed the experiments on the optimization and substrate scope for the anti-Markovnikov phosphate additions. J-M.M.G. performed the experiments on the optimization and substrate scope for the anti-Markovnikov sulfonate additions. D.J.W., J-M.M.G. and D.A.N. co-wrote the manuscript.

Corresponding author

Correspondence to David A. Nicewicz.

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Wilger, D., Grandjean, JM., Lammert, T. et al. The direct anti-Markovnikov addition of mineral acids to styrenes. Nature Chem 6, 720–726 (2014). https://doi.org/10.1038/nchem.2000

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