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Preparation and purification of zinc sulfinate reagents for drug discovery

Nature Protocols volume 8, pages 1042–1047 (2013)Cite this article

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Abstract

The present protocol details the synthesis of zinc bis(alkanesulfinate)s that can be used as general reagents for the formation of radical species. The zinc sulfinates described herein are generated from the corresponding sulfonyl chlorides by treatment with zinc dust. The products may be used crude, or a simple purification procedure may be performed to minimize incorporation of water and zinc chloride. Although the synthesis of the zinc sulfinate salts can generally be completed within 3 h, workup can take up to 24 h and purification can take up to 3 h. Following the steps in this protocol would enable the user to generate a small toolkit of zinc sulfinate reagents over the course of 1 week.

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Figure 1
Figure 2
Figure 3: Recently developed synthetic procedures that use zinc sulfinate reagents.

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Acknowledgements

The Baran research group works with Sigma-Aldrich in providing a portfolio of zinc-based reagents promoting difluoromethylation, trifluoromethylation, trifluoroethylation and isopropylation of aryl and heteroaryl motifs. This relationship does not constitute a competing financial interest. We thank T. Ryba and C. Thomas from Sigma-Aldrich for a donation of chemicals. Financial support for this work was provided by the US National Institutes of Health (research grant GM-073949 and a postdoctoral fellowship for R.D.B.), Pfizer (financial support and a fellowship for A.G.O.), the US-UK Fulbright Commission (postdoctoral fellowship for F.O.) and the Uehara Memorial Foundation (postdoctoral fellowship for Y.F.).

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Authors and Affiliations

  1. Department of Chemistry, The Scripps Research Institute, La Jolla, California, USA

    Fionn O'Hara, Ryan D Baxter, Alexander G O'Brien, Janice A Dixon, Yuta Fujiwara, Yoshihiro Ishihara & Phil S Baran

  2. Department of Chemistry, La Jolla Laboratories, Pfizer Inc., San Diego, California, USA

    Michael R Collins

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  1. Fionn O'Hara
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Contributions

F.O., R.D.B., A.G.O., J.A.D., Y.F. and P.S.B. designed the experiments; F.O., R.D.B., A.G.O., J.A.D. and Y.F. conducted the experiments; F.O., R.D.B., A.G.O., M.R.C., J.A.D., Y.F., Y.I. and P.S.B. analyzed the data and Y.I. and P.S.B. wrote the manuscript.

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Correspondence to Phil S Baran.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Data

Supplementary information. X-ray structures of TFMS•THF complex and DFMS, elemental analyses for all desired products and determination of chloride incorporation. (PDF 1862 kb)

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O'Hara, F., Baxter, R., O'Brien, A. et al. Preparation and purification of zinc sulfinate reagents for drug discovery. Nat Protoc 8, 1042–1047 (2013). https://doi.org/10.1038/nprot.2013.059

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