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An organic thiyl radical catalyst for enantioselective cyclization

Abstract

A diverse array of chiral organocatalysts have been developed that rely on acid–base interactions to promote enantioselective ionic reactions via the movement of electron pairs. The stereocontrol of radical reactions using organocatalysts is an alternative approach, and several studies have shown that synthetically useful reactivity can result by controlling the movement of single electrons. However, in these studies, it is still an acid–based organocatalyst which forms a closed-shell intermediate with substrate prior to the radical reaction and imparts chiral information, and use of a chiral organic radical directly as catalyst has only rarely been explored. Here, we report the design of an organic thiyl radical catalyst with a carefully designed chiral pocket constructed around a chiral thiol precatalyst. The resulting catalyst was used to effect highly diastereo- and enantioselective C–C bond-forming radical cyclizations.

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Figure 1: Initial foray into the development of the chiral organic radical catalyst.
Figure 2: Design of a new scaffold for enantioselective radical cyclization.
Figure 3: Synthesis of a new chiral thiol.

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Acknowledgements

This work was partially supported by a Grant-in-Aid for Scientific Research from the MEXT (Japan). Y.K. acknowledges a Grant-in-Aid for the Research Fellowship of JSPS for Young Scientists.

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Authors

Contributions

T.H. conceived the study and wrote the manuscript. T.H. and Y.K. designed experiments and Y.K. performed experiments. K.M. organized the research.

Corresponding author

Correspondence to Keiji Maruoka.

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The authors declare no competing financial interests.

Supplementary information

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Supplementary information (PDF 5067 kb)

Supplementary information

Crystallographic data for compound 2a' (CIF 30 kb)

Supplementary information

Crystallographic data for compound (S)-5b (CIF 50 kb)

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Hashimoto, T., Kawamata, Y. & Maruoka, K. An organic thiyl radical catalyst for enantioselective cyclization. Nature Chem 6, 702–705 (2014). https://doi.org/10.1038/nchem.1998

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