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Preparation of functionalized organoaluminiums by direct insertion of aluminium to unsaturated halides

Nature Chemistry volume 2, pages 313318 (2010) | Download Citation

Abstract

The preparation of polyfunctional organometallics is important in organic synthesis as these reagents are very popular nucleophiles. The preparation of functionalized aluminium reagents by direct insertion of aluminium powder is in general not possible. Such a reaction would be of special importance owing to the low price of aluminium compared with magnesium (it is half the price), the low toxicity of this metal and the chemoselectivity of the resultant organoaluminium reagents. We have now found that by adding catalytic amounts of selected metallic chlorides (TiCl4, BiCl3, InCl3 or PbCl2) in the presence of LiCl, aluminium powder inserts into various unsaturated iodides and bromides under mild conditions. These resulting new organoaluminium reagents undergo smooth Pd-catalysed cross-coupling and acylation reactions, as well as copper-catalysed allylic substitutions, affording various interesting products for pharmaceutical and material science applications.

  • Compound C7H4F3I

    1-Iodo-4-(trifluoromethyl)benzene

  • Compound C6H4BrF

    1-Bromo-2-fluorobenzene

  • Compound C7H7BrO

    1-Bromo-2-methoxybenzene

  • Compound C7H6BrClO

    1-Bromo-4-chloro-2-methoxybenzene

  • Compound C7H6BrClO

    2-Bromo-4-chloro-1-methoxybenzene

  • Compound C7H7BrS

    1-Bromo-2-methylsulfanyl-benzene

  • Compound C7H4BrF3

    1-Bromo-3-(trifluoromethyl)benzene

  • Compound C6H4BrCl

    1-Bromo-4-chlorobenzene

  • Compound C8H7BrO2

    Methyl 4-bromobenzoate

  • Compound C6H4BrNO2

    1-Bromo-4-nitrobenzene

  • Compound C14H8ClNOS

    S-4-Chlorophenyl 4-cyanobenzothioate

  • Compound C7H4BrF3

    1-Bromo-2-(trifluoromethyl)benzene

  • Compound C11H13BrO3

    4-Bromophenyl tert-butyl carbonate

  • Compound C8H7IO

    1-(4-Iodophenyl)ethanone

  • Compound C9H9IO2

    Ethyl 3-iodobenzoate

  • Compound C14H11FO2

    Methyl 2'-fluorobiphenyl-4-carboxylate

  • Compound C13H11NO3

    2-Methoxy-4'-nitrobiphenyl

  • Compound C15H10ClNO2

    4-(4-Chloro-2-methoxybenzoyl)benzonitrile

  • Compound C14H10ClF3O

    5-Chloro-2-methoxy-6'-(trifluoromethyl)biphenyl

  • Compound C18H20O3S

    tert-Butyl 2'-(methylthio)biphenyl-4-yl carbonate

  • Compound C15H11F3O

    1-(3'-(Trifluoromethyl)biphenyl-4-yl)ethanone

  • Compound C15H13ClO2

    Ethyl 4'-chlorobiphenyl-3-carboxylate

  • Compound C8H9I

    1-Iodo-3,5-dimethylbenzene

  • Compound C6H4ClI

    1-Chloro-3-iodobenzene

  • Compound C11H13I

    1-Iodo-2-(3-methylbut-3-enyl)benzene

  • Compound C8H13I

    (1-Iodovinyl)cyclohexane

  • Compound C6H4FI

    1-Fluoro-3-iodobenzene

  • Compound C7H4F3IO

    1-Iodo-3-(trifluoromethoxy)benzene

  • Compound C13H8BrClOS

    S-4-Chlorophenyl 4-bromobenzothioate

  • Compound C6H9BrO2

    Ethyl 2-(bromomethyl)acrylate

  • Compound C6H5BrOS

    1-(5-Bromothiophen-2-yl)ethanone

  • Compound C8H6BrN

    3-(Bromomethyl)benzonitrile

  • Compound C8H8BrNO2

    Ethyl 5-bromonicotinate

  • Compound C6H3BrN2

    5-Bromonicotinonitrile

  • Compound C9H11IN2O4

    Ethyl 4-iodo-2,6-dimethoxypyrimidine-5-carboxylate

  • Compound C15H13BrO

    (4-Bromophenyl)(3,5-dimethylphenyl)methanone

  • Compound C12H13ClO2

    Ethyl 2-(3-chlorobenzyl)acrylate

  • Compound C17H18OS

    1-(5-(2-(3-Methylbut-3-enyl)phenyl)thiophen-2-yl)ethanone

  • Compound C16H19N

    3-(2-Cyclohexylallyl)benzonitrile

  • Compound C14H12FNO2

    Ethyl 5-(3-fluorophenyl)nicotinate

  • Compound C13H7F3N2O

    5-(3-(Trifluoromethoxy)phenyl)nicotinonitrile

  • Compound C16H15F3N2O4

    Ethyl 2,4-dimethoxy-6-(4-(trifluoromethyl)phenyl)pyrimidine-5-carboxylate

  • Compound C7H7BrO2S

    Ethyl 5-bromothiophene-2-carboxylate

  • Compound C9H9IO2

    Ethyl 2-iodobenzoate

  • Compound C7H7BrO3

    Ethyl 5-bromofuran-2-carboxylate

  • Compound C11H14INO

    N,N-Diethyl-3-iodobenzamide

  • Compound C7H5BrO

    4-Bromobenzaldehyde

  • Compound C6H9Br

    3-Bromocyclohex-1-ene

  • Compound C10H11IO

    1-(4-Iodophenyl)-2-methylpropan-1-one

  • Compound C3H5Br

    3-Bromoprop-1-ene

  • Compound C7H4BrN

    2-Bromobenzonitrile

  • Compound C7H6BrF

    1-Bromo-4-fluoro-2-methylbenzene

  • Compound C14H12O3S

    Ethyl 5-(4-formylphenyl)thiophene-2-carboxylate

  • Compound C15H18O2

    Ethyl 3-(cyclohex-2-enyl)benzoate

  • Compound C19H20O3

    Ethyl 4'-isobutyrylbiphenyl-3-carboxylate

  • Compound C12H14O2

    Ethyl 2-allylbenzoate

  • Compound C14H11NO3

    Ethyl 5-(2-cyanophenyl)furan-2-carboxylate

  • Compound C18H20FNO

    N,N-Diethyl-4'-fluoro-6'-methylbiphenyl-3-carboxamide

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Acknowledgements

Y.-H.C. thanks the Humboldt Foundation for financial support. We thank the Fonds der Chemischen Industrie, the DFG and the European Research Council for financial support. We thank Chemetall and BASF for the generous gift of chemicals.

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Affiliations

  1. Department Chemie und Biochemie, Ludwig-Maximilians-Universität München, Butenandtstrasse 5-13, Haus F. 81377 München, Germany

    • Tobias Blümke
    • , Yi-Hung Chen
    • , Zhihua Peng
    •  & Paul Knochel

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Contributions

T.B. and Y.-H.C. contributed equally to this work. Z.P. assisted in conducting and analysing the chemical experiments. P.K. designed and directed the project and wrote the manuscript with contributions from Y.-H.C. and T.B. All authors contributed to discussions.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Paul Knochel.

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https://doi.org/10.1038/nchem.590

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