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Catalytic, stereospecific syn-dichlorination of alkenes

Nature Chemistry volume 7, pages 146–152 (2015)Cite this article

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Abstract

As some of the oldest organic chemical reactions known, the ionic additions of elemental halogens such as bromine and chlorine to alkenes are prototypical examples of stereospecific reactions, typically delivering vicinal dihalides resulting from anti-addition. Although the invention of enantioselective variants is an ongoing challenge, the ability to overturn the intrinsic anti-diastereospecificity of these transformations is also a largely unsolved problem. Here, we describe the first catalytic, syn-stereospecific dichlorination of alkenes, employing a group transfer catalyst based on a redox-active main group element (selenium). With diphenyl diselenide (PhSeSePh) (5 mol%) as the pre-catalyst, benzyltriethylammonium chloride (BnEt3NCl) as the chloride source and an N-fluoropyridinium salt as the oxidant, a wide variety of functionalized cyclic and acyclic 1,2-disubstituted alkenes, including simple allylic alcohols, deliver syn-dichlorides with exquisite stereocontrol. This methodology is expected to find applications in streamlining the synthesis of polychlorinated natural products such as the chlorosulfolipids.

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Figure 1: The vicinal dichloride motif in natural products.
Figure 2: Identification of E2 elimination by-products.
Figure 3: Proposed catalytic cycle for the selenium-catalysed syn-dichlorination of alkenes.

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Acknowledgements

The authors acknowledge the National Institutes of Health (GM R01-085235) for financial support. S.T-C.E. thanks the Agency for Science, Technology and Research of Singapore (A*STAR) for a postdoctoral fellowship.

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Author notes

  1. Alexander J. Cresswell and Stanley T.-C. Eey: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Chemistry, Roger Adams Laboratory, University of Illinois, Urbana, 61801, Illinois, USA

    Alexander J. Cresswell, Stanley T.-C. Eey & Scott E. Denmark

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  1. Alexander J. Cresswell
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  2. Stanley T.-C. Eey
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Contributions

A.J.C. planned and carried out the experimental work and initial optimization. S.T-C.E. completed the experimental work and final characterizations. S.E.D. directed and coordinated the project. A.J.C. wrote the manuscript with the assistance of the other authors.

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Correspondence to Scott E. Denmark.

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The authors declare no competing financial interests.

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Cresswell, A., Eey, SC. & Denmark, S. Catalytic, stereospecific syn-dichlorination of alkenes. Nature Chem 7, 146–152 (2015). https://doi.org/10.1038/nchem.2141

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