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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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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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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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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DOI: https://doi.org/10.1038/nchem.1452
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