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Direct catalytic cross-coupling of organolithium compounds

Nature Chemistry volume 5, pages 667672 (2013) | Download Citation

This article has been updated

Abstract

Catalytic carbon–carbon bond formation based on cross-coupling reactions plays a central role in the production of natural products, pharmaceuticals, agrochemicals and organic materials. Coupling reactions of a variety of organometallic reagents and organic halides have changed the face of modern synthetic chemistry. However, the high reactivity and poor selectivity of common organolithium reagents have largely prohibited their use as a viable partner in direct catalytic cross-coupling. Here we report that in the presence of a Pd-phosphine catalyst, a wide range of alkyl-, aryl- and heteroaryl-lithium reagents undergo selective cross-coupling with aryl- and alkenyl-bromides. The process proceeds quickly under mild conditions (room temperature) and avoids the notorious lithium halogen exchange and homocoupling. The preparation of key alkyl-, aryl- and heterobiaryl intermediates reported here highlights the potential of these cross-coupling reactions for medicinal chemistry and material science.

  • Compound C11H16O

    1-Butyl-4-methoxybenzene

  • Compound C12H19N

    4-Butyl-N,N-dimethylaniline

  • Compound C10H13Cl

    1-Butyl-4-chlorobenzene

  • Compound C14H16

    1-Butylnaphthalene

  • Compound C14H16

    2-Butylnaphthalene

  • Compound C11H10

    2-Methylnaphthalene

  • Compound C17H18

    2-Butyl-9H-fluorene

  • Compound C14H12

    2-Methyl-9H-fluorene

  • Compound C23H40O

    1-Hexadecyl-4-methoxybenzene

  • Compound C13H20O

    1-Hexyl-4-methoxybenzene

  • Compound C14H23N

    4-Hexyl-N,N-dimethylaniline

  • Compound C11H18OSi

    (4-Methoxybenzyl)trimethylsilane

  • Compound C10H14Cl2Si

    (3,5-Dichlorobenzyl)trimethylsilane

  • Compound C14H24Si

    (4-(tert-Butyl)benzyl)trimethylsilane

  • Compound C14H18SSi

    Trimethyl((5-phenylthiophen-2-yl)methyl)silane

  • Compound C20H26

    4,4'-Dibutyl-1,1'-biphenyl

  • Compound C12H16

    (E)-Hex-1-enylbenzene

  • Compound C9H18

    (Z)-Non-2-ene

  • Compound C13H18O2

    2-(4-Butylphenyl)-1,3-dioxolane

  • Compound C11H16O

    4-Butylbenzyl alcohol

  • Compound C9H10O2

    Methyl 4-methylbenzoate

  • Compound C11H17N

    4-Isopropyl-N,N-dimethylaniline

  • Compound C10H14O

    1-Isopropyl-4-methoxybenzene

  • Compound C11H16O

    1-(sec-Butyl)-4-methoxybenzene

  • Compound C10H13Cl

    1-(sec-Butyl)-4-chlorobenzene

  • Compound C10H12Cl2

    1-Butyl-3,5-dichlorobenzene

  • Compound C13H12O

    4-Methoxybiphenyl

  • Compound C14H15N

    N,N-Dimethyl-[1,1'-biphenyl]-4-amine

  • Compound C12H9Cl

    4-Chloro-1,1'-biphenyl

  • Compound C16H12

    2-Phenylnaphthalene

  • Compound C14H11N

    5-Phenyl-1H-indole

  • Compound C11H7F3S

    2-(3-Trifluoromethylphenyl)thiophene

  • Compound C11H10OS

    2-(4-Methoxyphenyl)thiophene

  • Compound C11H14

    α,β,β-Trimethylstyrene

  • Compound C7H8S

    (Z)-2-(Prop-1-en-1-yl)thiophene

  • Compound C14H14

    2,3-Dimethylbiphenyl

  • Compound C15H16O

    4'-Methoxy-2,6-dimethyl-1,1'-biphenyl

  • Compound C16H19N

    (2',6'-Dimethylbiphenyl-4yl)dimethylamine

  • Compound C14H11F3O

    4'-Methoxy-3-(trifluoromethyl)-1,1'-biphenyl

  • Compound C17H14O

    2-(4-Methoxyphenyl)naphthalene

  • Compound C11H10O2

    2-(4-Methoxyphenyl)furan

  • Compound C10H7ClO

    2-(4-Chlorophenyl)furan

  • Compound C15H16O3

    4'-Methoxy-2-(methoxymethoxy)-1,1'-biphenyl

  • Compound C18H16O2

    2-(2-(Methoxymethoxy)phenyl)naphthalene

  • Compound C37H46S2

    2,7-Dithienyl-9,9-dioctylfluorene

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Change history

  • 17 June 2013

    In the version of this Article originally published online, there are three instances where the compound 2u should have been 2x: twice in Table 1, and once in the section 'Pd-catalysed cross-coupling with alkyllithium reagents.' Also in that section, 2s-2v should have been 2v-2y. These errors have been corrected in the HTML and PDF versions of the Article.

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Acknowledgements

The authors thank the Netherlands Organization for Scientific Research (NWO-CW), the National Research School Catalysis (NRSC-C) and the European Research Council (ERC advanced grant 227897 to B.L.F.) for financial support.

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Affiliations

  1. Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands

    • Massimo Giannerini
    • , Martín Fañanás-Mastral
    •  & Ben L. Feringa

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Contributions

M.G. and M.F.-M. performed the experiments. M.G., M.F.-M. and B.L.F. designed the experiments, analysed the data and wrote the manuscript. B.L.F. guided the research.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Ben L. Feringa.

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DOI

https://doi.org/10.1038/nchem.1678

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