10.1002/chem.201802352
Chemistry - A European Journal
COMMUNICATION
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protocol was amenable to scale-up, giving 3a in 86% yield on a 5
mmol scale.
It is important to highlight that sulfur containing compounds often
show different biological activities and have important
applications in the pharmaceutical industry. Thioethers,
sulfoxides, and sulfones are moieties present in most sulfur-
containing drugs.[21] Therefore, in order to demonstrate the further
synthetic applications of these methylthiomethylated products, 3a
was successfully oxidized to its corresponding sulfoxide 10 and
sulfone 11 counterparts in high yields.
In summary, we have disclosed a heteroarene C–H alkylation
strategy enabled by visible light using DMSO as a carbon source.
Moreover, an unprecedented switch in reactivity between
methylation and methylthiomethylation was accomplished under
reagent-controlled conditions. This strategy represents, to the
best of our knowledge, the first reported formation of
methylthiomethyl radicals to be used in heteroarene
functionalization. We believe this direct C–H functionalization
method of installing small alkyl groups will find a wide application
in medicinal chemistry for the rapid and straightforward
diversification of relevant pharmacophores.
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Acknowledgements
We thank Dr. Sara Cembellin, Dr. Kathryn Chepiga, Dr. Michael
J. James, Medine Kara, Max Lübbesmeyer, Luca Schwarz, and
Dr. Manuel van Gemmeren for experimental assistance and
helpful discussions. Generous financial support from the
Alexander von Humboldt Foundation (T.P.), Deutsche
Forschungsgemeinschaft (Leibniz Award), and the NRW
Graduate School of Chemistry (A.T.A.) are gratefully
acknowledged.
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Keywords: heteroarenes • methylation • methylthiomethylation •
CH functionalization • photoredox catalysis
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