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Catalytic asymmetric carbon–carbon bond formation via allylic alkylations with organolithium compounds

Nature Chemistry volume 3, pages 377381 (2011) | Download Citation

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Abstract

Carbon–carbon bond formation is the basis for the biogenesis of nature's essential molecules. Consequently, it lies at the heart of the chemical sciences. Chiral catalysts have been developed for asymmetric C–C bond formation to yield single enantiomers from several organometallic reagents. Remarkably, for extremely reactive organolithium compounds, which are among the most broadly used reagents in chemical synthesis, a general catalytic methodology for enantioselective C–C formation has proven elusive, until now. Here, we report a copper-based chiral catalytic system that allows carbon–carbon bond formation via allylic alkylation with alkyllithium reagents, with extremely high enantioselectivities and able to tolerate several functional groups. We have found that both the solvent used and the structure of the active chiral catalyst are the most critical factors in achieving successful asymmetric catalysis with alkyllithium reagents. The active form of the chiral catalyst has been identified through spectroscopic studies as a diphosphine copper monoalkyl species.

  • Compound C36H44FeP2

    (R)-1-[(Sp)-2-(Diphenylphosphino)ferrocenyl]ethyldicyclohexylphosphine

  • Compound C36H44FeP2

    (S)-1-[(Rp)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldiphenylphosphine

  • Compound C52H48P2

    2,2'-Bis(bis(3,5-dimethylphenyl)phosphino)-1,1'-binaphthalene

  • Compound C36H30NO2P

    N,N-Bis((R)-1-phenylethyl)dinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphepin-4-amine

  • Compound C38H34NO4P

    N,N-Bis((S)-1-(2-methoxyphenyl)ethyl)dinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphepin-4-amine

  • Compound C43H39FeNP2

    (R,Rp)-Taniaphos

  • Compound C9H9Br

    (E)-(3-Bromoprop-1-en-1-yl)benzene

  • Compound C9H9Cl

    (E)-(3-Chloroprop-1-en-1-yl)benzene

  • Compound C13H11Br

    (E)-1-(3-Bromoprop-1-en-1-yl)naphthalene

  • Compound C9H8BrCl

    (E)-1-(3-Bromoprop-1-en-1-yl)-4-chlorobenzene

  • Compound C9H8Br2

    (E)-1-Bromo-4-(3-bromoprop-1-en-1-yl)benzene

  • Compound C8H15Br

    (E)-1-Bromooct-2-ene

  • Compound C11H13BrO

    (E)-(((4-Bromobut-2-en-1-yl)oxy)methyl)benzene

  • Compound C16H22BrNO4S

    (E)-tert-Butyl (4-bromobut-2-en-1-yl)(tosyl)carbamate

  • Compound C10H9BrO2

    (E)-3-Bromoprop-1-en-1-yl benzoate

  • Compound C4H7BrO

    (E)-4-Bromobut-2-en-1-ol

  • Compound CH3Li

    Methyl lithium

  • Compound C2H5Li

    Ethyl lithium

  • Compound C4H9Li

    n-Butyllithium

  • Compound C6H13Li

    n-Hexyllithium

  • Compound C3H7Li

    Isopropyllithium

  • Compound C4H9Li

    sec-Butyllithium

  • Compound C6H5Li

    Phenyllithium

  • Compound C10H12

    (+)-(S)-But-3-en-2-ylbenzene

  • Compound C11H14

    (+)-(S)-Pent-1-en-3-ylbenzene

  • Compound C13H18

    (+)-(S)-Hept-1-en-3-ylbenzene

  • Compound C15H22

    (+)-(S)-Non-1-en-3-ylbenzene

  • Compound C12H16

    (+)-(S)-(4-Methylpent-1-en-3-yl)benzene

  • Compound C13H18

    (+)-(3R,4R/S)-(4-Methylhex-1-en-3-yl)benzene

  • Compound C14H14

    (-)-(S)-1-(But-3-en-2-yl)naphthalene

  • Compound C17H20

    (-)-(S)-1-(Hept-1-en-3-yl)naphthalene

  • Compound C10H11Cl

    (+)-(S)-1-(But-3-en-2-yl)-4-chlorobenzene

  • Compound C11H13Cl

    (+)-(S)-1-Chloro-4-(pent-1-en-3-yl)benzene

  • Compound C13H17Cl

    (+)-(S)-1-Chloro-4-(hept-1-en-3-yl)benzene

  • Compound C15H21Cl

    (+)-(S)-1-Chloro-4-(non-1-en-3-yl)benzene

  • Compound C15H13Cl

    (-)-(S)-1-Chloro-4-(1-phenylallyl)benzene

  • Compound C13H17Br

    (+)-(S)-1-Bromo-4-(hept-1-en-3-yl)benzene

  • Compound C10H20

    (R)-3-Ethyloct-1-ene

  • Compound C12H16O

    (-)-(S)-(((2-Methylbut-3-en-1-yl)oxy)methyl)benzene

  • Compound C13H18O

    (+)-(S)-(((2-Ethylbut-3-en-1-yl)oxy)methyl)benzene

  • Compound C15H22O

    (+)-(S)-(((2-Vinylhexyl)oxy)methyl)benzene

  • Compound C17H26O

    (+)-(S)-(((2-Vinyloctyl)oxy)methyl)benzene

  • Compound C18H27NO4S

    (-)-(S)-tert-Butyl (2-ethylbut-3-en-1-yl)(tosyl)carbamate

  • Compound C11H12O2

    (+)-(S)-But-3-en-2-yl benzoate

  • Compound C14H18O2

    (+)-(S)-Hept-1-en-3-yl benzoate

  • Compound C8H16O

    (S)-2-Vinylhexan-1-ol

  • Compound C10H12

    (E)-But-1-en-1-ylbenzene

  • Compound C11H14

    (E)-Pent-1-en-1-ylbenzene

  • Compound C13H18

    (E)-Hept-1-en-1-ylbenzene

  • Compound C15H22

    (E)-Non-1-en-1-ylbenzene

  • Compound C12H16

    (E)-(4-Methylpent-1-en-1-yl)benzene

  • Compound C13H18

    (E)-(4-Methylhex-1-en-1-yl)benzene

  • Compound C14H14

    (E)-1-(But-1-en-1-yl)naphthalene

  • Compound C17H20

    (E)-1-(Hept-1-en-1-yl)naphthalene

  • Compound C10H11Cl

    (E)-1-(But-1-en-1-yl)-4-chlorobenzene

  • Compound C11H13Cl

    (E)-1-Chloro-4-(pent-1-en-1-yl)benzene

  • Compound C13H17Cl

    (E)-1-Chloro-4-(hept-1-en-1-yl)benzene

  • Compound C15H21Cl

    (E)-1-Chloro-4-(non-1-en-1-yl)benzene

  • Compound C15H13Cl

    (E)-1-Chloro-4-(3-phenylprop-1-en-1-yl)benzene

  • Compound C13H17Br

    (E)-1-Bromo-4-(hept-1-en-1-yl)benzene

  • Compound C10H20

    (E)-Dec-4-ene

  • Compound C12H16O

    (E)-((Pent-2-en-1-yloxy)methyl)benzene

  • Compound C13H18O

    (E)-((Hex-2-en-1-yloxy)methyl)benzene

  • Compound C15H22O

    (E)-((Oct-2-en-1-yloxy)methyl)benzene

  • Compound C17H26O

    (E)-((Dec-2-en-1-yloxy)methyl)benzene

  • Compound C18H27NO4S

    (E)-tert-Butyl hex-2-en-1-yl(tosyl)carbamate

  • Compound C11H12O2

    (E)-But-1-en-1-yl benzoate

  • Compound C14H18O2

    (E)-Hept-1-en-1-yl benzoate

  • Compound C8H16O

    (E)-Oct-2-en-1-ol

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Change history

  • 15 March 2011

    In the version of this Article originally published, the Acknowledgements section was incorrect. This error has now been corrected in all versions of the Article.

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Acknowledgements

The authors acknowledge the Netherlands Organization for Scientific Research (NWO-CW) and the National Research School Catalysis (NRSC-C) for financial support. M.P. thanks the Xunta de Galicia for an Angeles Alvariño contract and Fondo Social Europeo. M.F.-M. thanks the Spanish Ministry of Science and Innovation (MICINN) for a postdoctoral fellowship.

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Affiliations

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

    • Manuel Pérez
    • , Martín Fañanás-Mastral
    • , Pieter H. Bos
    • , Alena Rudolph
    • , Syuzanna R. Harutyunyan
    •  & Ben L. Feringa

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Contributions

M.P. and M.F.-M. studied solvent effects and optimized the reaction conditions. P.H.B. performed ligand screening. A.R. performed copper salt screening. S.R.H. carried out NMR studies. M.P., M.F.-M, P.H.B. and A.R. evaluated the scope of the organolithium addition reaction. All authors contributed to designing the experiments, analysing the data and editing the manuscript. S.R.H. and B.L.F. guided the research and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Syuzanna R. Harutyunyan or Ben L. Feringa.

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DOI

https://doi.org/10.1038/nchem.1009

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