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Rhodium-catalysed asymmetric allylic arylation of racemic halides with arylboronic acids

Nature Chemistry volume 7, pages 935939 (2015) | Download Citation

Abstract

Csp2Csp2 cross-coupling reactions between arylboronic acid and aryl halides are widely used in both academia and industry and are strategically important in the development of new agrochemicals and pharmaceuticals. Csp2Csp3 cross-coupling reactions have been developed, but enantioselective variations are rare and simply retaining the stereochemistry is a problem. Here we report a highly enantioselective Csp2Csp3 bond-forming method that couples arylboronic acids to racemic allyl chlorides. Both enantiomers of a cyclic chloride are converted into a single enantiomer of product via a dynamic kinetic asymmetric transformation. This Rh-catalysed method uses readily available and inexpensive building blocks and is mild and broadly applicable. For electron-deficient, electron-rich or ortho-substituted boronic acids better results are obtained with racemic allyl bromides. Oxygen substitution in the allyl halide is tolerated and the products can be functionalized to provide diverse building blocks. The approach fills a significant gap in the methods for catalytic asymmetric synthesis.

  • Compound C6H9Cl

    3-chlorocyclohex-1-ene

  • Compound C5H7Cl

    3-chlorocyclopent-1-ene

  • Compound C7H11Cl

    3-chlorocyclohept-1-ene

  • Compound C6H9Br

    3-bromocyclohex-1-ene

  • Compound C5H7ClO

    3-chloro-3,6-dihydro-2H-pyran

  • Compound C12H14

    (S)-cyclohex-2-enylbenzene

  • Compound C16H16

    (S)-2-(cyclohex-2-en-1-yl)naphthalene

  • Compound C13H16

    (S)-3-(3-methylphenyl)cyclohexene

  • Compound C13H16

    (S)-3-(4-methylphenyl)cyclohexene

  • Compound C13H16O

    (S)-3-(4-methoxyphenyl)cyclohexene

  • Compound C13H13F3

    (S)-3-(3-trifluoromethylphenyl)cyclohexene

  • Compound C14H16O2

    (S)-3-(3-Methoxycarbonylphenyl)cyclohexene

  • Compound C12H13F

    (S)-3-(3-fluorophenyl)cyclohexene

  • Compound C12H13Cl

    (S)-3-(4-chlorophenyl)cyclohexene

  • Compound C12H13Cl

    (S)-3-(3-chlorophenyl)cyclohexene

  • Compound C12H13Br

    (S)-3-(3-bromophenyl)cyclohexene

  • Compound C11H12

    (S)-cyclopent-2-enylbenzene

  • Compound C13H16

    (S)-cyclohept-2-enylbenzene

  • Compound C13H16

    (S)-3-(2-methylphenyl)cyclohexene

  • Compound C12H13NO2

    (S)-3-(3-nitrophenyl)cyclohexene

  • Compound C13H16O

    (S)-3-(2-methoxyphenyl)cyclohexene

  • Compound C12H12F2

    (S)-3-(2,4-difluorophenyl)cyclohexene

  • Compound C19H20O

    (S)-3-(4-benzyloxyphenyl)cyclohexene

  • Compound C18H28OSi

    (S)-3-(4-tert-butyldimethylsilyloxyphenyl)cyclohexene

  • Compound C11H12O

    (S)-3-phenyl-3,6-dihydro-2H-pyran

  • Compound C15H14O

    (S)-3-(naphthalen-2-yl)-3,6-dihydro-2H-pyran

  • Compound C12H14O

    (S)-3-(m-tolyl)-3,6-dihydro-2H-pyran

  • Compound C11H11ClO

    (S)-3-(4-chlorophenyl)-3,6-dihydro-2H-pyran

  • Compound C12H14O2

    (S)-3-(4-methoxyphenyl)-3,6-dihydro-2H-pyran

  • Compound C14H16

    (S,E)-(2-(cyclohex-2-en-1-yl)vinyl)benzene

  • Compound C15H18

    (S,E)-1-(2-(cyclohex-2-en-1-yl)vinyl)-3-methylbenzene

  • Compound C14H15F

    (S,E)-1-(2-(cyclohex-2-en-1-yl)vinyl)-3-fluorobenzene

  • Compound C12H13Cl

    cis-3-chloro-5-phenylcyclohexene

  • Compound C12H13Cl

    trans-3-chloro-5-phenylcyclohexene

  • Compound C18H18

    (S,S)-cis-3,5-diphenylcyclohexene

  • Compound C18H18

    (S,R)-trans-3,5-diphenylcyclohexene

  • Compound C12H14O2

    (R)-2-phenylhexanedial

  • Compound C12H14Br2

    ((1R,2S,3S)-2,3-dibromocyclohexyl)benzene

  • Compound C12H15BrO2

    (S,Z)-5-bromo-2-(4-methoxyphenyl)pent-3-en-1-ol

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Acknowledgements

We acknowledge financial support from the Engineering and Physical Sciences Research Council (EP/H003711/1, a Career Acceleration Fellowship to S.F.).

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Affiliations

  1. Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK

    • Mireia Sidera
    •  & Stephen P. Fletcher

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Contributions

M.S. performed the experiments and S.F. guided the research. Both authors contributed to designing the experiments, analysing the data and writing the manuscript.

Competing interests

The authors are named as inventors on a UK patent application filed by Isis Innovation, which is the technology transfer arm of the University of Oxford.

Corresponding author

Correspondence to Stephen P. Fletcher.

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DOI

https://doi.org/10.1038/nchem.2360