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CROSS-COUPLING

Forged in iron

Fifty years ago, Kochi reported the iron-catalysed cross-coupling of alkenyl halides and alkyl Grignard reagents. Sparking a cross-coupling revolution, we reflect on the impact of this achievement and the importance of iron in the development of cross-coupling catalysis.

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Fig. 1: Metal-catalysed cross-coupling in organic chemistry arguably began with the work of Kochi and colleagues.

References

  1. 1.

    Johansson Seechurn, C. C. C., Kitching, M. O., Colacot, T. J. & Snieckus, V. Palladium-catalyzed cross-coupling: a historical contextual perspective to the 2010 Nobel Prize. Angew. Chem. Int. Ed. 51, 5062–5085 (2012).

    CAS  Article  Google Scholar 

  2. 2.

    Tamura, M. & Kochi, J. K. Vinylation of Grignard reagents. Catalysis by iron. J. Am. Chem. Soc. 93, 1487–1489 (1971).

    CAS  Article  Google Scholar 

  3. 3.

    Kharasch, M. S. & Fields, E. K. Factors determining the course and mechanisms of Grignard reactions. IV. The effect of metallic halides on the reaction of aryl Grignard reagents and organic halides. J. Am. Chem. Soc. 63, 2316–2320 (1941).

    CAS  Article  Google Scholar 

  4. 4.

    Smith, R. S. & Kochi, J. K. Mechanistic studies of iron catalysis in the cross coupling of alkenyl halides and Grignard reagents. J. Org. Chem. 41, 502–509 (1976).

    CAS  Article  Google Scholar 

  5. 5.

    Neidig, M. L. et al. Development and evolution of mechanistic understanding in iron-catalyzed cross-coupling. Acc. Chem. Res. 52, 140–150 (2019).

    CAS  Article  Google Scholar 

  6. 6.

    Muñoz, S. B. III, Daifuku, S. L., Brennessel, W. W. & Neidig, M. L. Isolation, characterization, and reactivity of Fe8Me12: Kochi’s S = 1/2 species in iron-catalyzed cross-couplings with MeMgBr and ferric salts. J. Am. Chem. Soc. 138, 7492–7495 (2016).

    Article  Google Scholar 

  7. 7.

    Cahiez, G. & Avedissian, H. Highly stereo- and chemoselective iron-catalyzed alkenylation of organomagnesium compounds. Synthesis 8, 1199–1205 (1998).

    Article  Google Scholar 

  8. 8.

    Fürstner, A. & Leitner, A. Iron-catalyzed cross-coupling reactions of alkyl-Grignard reagents with aryl chlorides, tosylates, and triflates. Angew. Chem. Int. Ed. 41, 609–612 (2002).

    Article  Google Scholar 

  9. 9.

    Nakamura, M., Matsuo, K., Ito, S. & Nakamura, E. Iron-catalyzed cross-coupling of primary and secondary alkyl halides with aryl Grignard reagents. J. Am. Chem. Soc. 126, 3686–3687 (2004).

    CAS  Article  Google Scholar 

  10. 10.

    Bedford, R. B. et al. Iron–phosphine, –phosphite, –arsine, and –carbene catalysts for the coupling of primary and secondary alkyl halides with aryl Grignard reagents. J. Org. Chem. 71, 1104–1110 (2006).

    CAS  Article  Google Scholar 

Download references

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Correspondence to Michael L. Neidig.

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Neate, P.G.N., Neidig, M.L. Forged in iron. Nat Rev Chem 5, 223–224 (2021). https://doi.org/10.1038/s41570-021-00259-4

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