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Engaging unactivated alkyl, alkenyl and aryl iodides in visible-light-mediated free radical reactions

Nature Chemistry volume 4, pages 854–859 (2012)Cite this article

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Abstract

Radical reactions are a powerful class of chemical transformations. However, the formation of radical species to initiate these reactions has often required the use of stoichiometric amounts of toxic reagents, such as tributyltin hydride. Recently, the use of visible-light-mediated photoredox catalysis to generate radical species has become popular, but the scope of these radical precursors has been limited. Here, we describe the identification of reaction conditions under which photocatalysts such as fac-Ir(ppy)3 can be utilized to form radicals from unactivated alkyl, alkenyl and aryl iodides. The generated radicals undergo reduction via hydrogen atom abstraction or reductive cyclization. The reaction protocol utilizes only inexpensive reagents, occurs under mild reaction conditions, and shows exceptional functional group tolerance. Reaction efficiency is maintained upon scale-up and decreased catalyst loading, and the reaction time can be significantly shortened when the reaction is performed in a flow reactor.

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Figure 1: Visible-light-active photocatalysts and representative examples of compounds capable of undergoing radical reductive cleavage.
Figure 2: The reduction protocol allows for simultaneous scale-up and lower catalyst loading, and reaction times are shortened when the reaction is run in a flow reactor.
Figure 3: Experimental evidence for proposed mechanistic pathway.

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Acknowledgements

The authors acknowledge financial support for this research from the NSF (CHE-1056568), the Alfred P. Sloan Foundation, Amgen and Boehringer Ingelheim. J.D.N. thanks AstraZeneca for a graduate fellowship and E.M.D. thanks the Boston University Undergraduate Research Program for research support. NMR (CHE-0619339) and mass spectrometry (CHE-0443618) facilities at Boston University are supported by the NSF. The authors thank J.W. Tucker for experimental assistance.

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  1. Department of Chemistry, Boston University, 590 Commonwealth Avenue, Boston, 02215, Massachusetts, USA

    John D. Nguyen, Erica M. D'Amato, Jagan M. R. Narayanam & Corey R. J. Stephenson

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J.D.N., E.M.D. and J.M.R.N. performed the experiments. All authors conceived and designed the experiments, analysed the data, contributed to discussions and wrote the manuscript.

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Correspondence to Corey R. J. Stephenson.

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Nguyen, J., D'Amato, E., Narayanam, J. et al. Engaging unactivated alkyl, alkenyl and aryl iodides in visible-light-mediated free radical reactions. Nature Chem 4, 854–859 (2012). https://doi.org/10.1038/nchem.1452

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