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Photo-induced iodination of aryl halides under very mild conditions

Abstract

Aryl iodides are important precursors in synthetic chemistry that form carbon–carbon and carbon–heteroatom bonds. Most methods use transition-metal catalysts, which need to be scrupulously removed before the compounds can be used in the pharmaceutical and electronics industries, where only parts-per-million levels of transition metals are allowed. The aromatic Finkelstein iodination reaction is a powerful method of preparing valuable aryl iodides from cheap but less reactive aryl bromides and chlorides. This protocol describes a transition metal–free method for a photo-induced aromatic Finkelstein iodination reaction that is performed at room temperature (20 °C). With common aromatic bromides and sodium iodide (NaI) as the starting materials, as well as a catalytic amount of I2 as an additive, the corresponding aromatic iodides can be synthesized in yields ranging from 56 to 93% under UV light irradiation in the absence of any metal catalysts. Various functional groups such as nitrile, ester and amino can be tolerated, which will facilitate the further functionalization of the aromatic iodides. The procedure normally requires 38–40 h to complete.

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Figure 1: Applications of aryl halides in organic synthesis.
Figure 2: Current approaches to aromatic halogen exchange.
Figure 3: Hypothesis for the mechanism of this photo-induced aromatic Finkelstein reaction.
Figure 4: Examples of aryl iodides that we have prepared at room temperature (rt) with UV light (254 nm) using this protocol.
Figure 5: Reaction setup for Step 1.
Figure 6: System degassing by the freeze–pump–thaw operation.
Figure 7: Photoreaction carried out in the LZC-4V photoreactor.
Figure 8: Reaction setup for gram-scale procedure.
Figure 9: Monitoring the reaction by GC–MS.
Figure 10

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Acknowledgements

This work was financially supported by the Canada Research Chair (Tier 1) foundation, the Natural Sciences and Engineering Research Council of Canada, the Fonds de recherchésur la nature et les technologies, the Canada Foundation for Innovation (CFI) and McGill University.

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Contributions

L.L. and W.L. designed the study; L.L. optimized and performed the experiments and W.L. discovered the initial reaction; L.L., W.L., X.M., C.-J.L. and Z.M. wrote the manuscript; C.-J.L. and Z.M. initiated and supervised the project; all authors discussed the results and commented on the manuscript.

Corresponding authors

Correspondence to Zetian Mi or Chao-Jun Li.

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The authors declare no competing financial interests.

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Li, L., Liu, W., Mu, X. et al. Photo-induced iodination of aryl halides under very mild conditions. Nat Protoc 11, 1948–1954 (2016). https://doi.org/10.1038/nprot.2016.125

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