Article

Site-selective oxidation, amination and epimerization reactions of complex polyols enabled by transfer hydrogenation

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Abstract

Polyoxygenated hydrocarbons that bear one or more hydroxyl groups comprise a large set of natural and synthetic compounds, often with potent biological activity. In synthetic chemistry, alcohols are important precursors to carbonyl groups, which then can be converted into a wide range of oxygen- or nitrogen-based functionality. Therefore, the selective conversion of a single hydroxyl group in natural products into a ketone would enable the selective introduction of unnatural functionality. However, the methods known to convert a simple alcohol, or even an alcohol in a molecule that contains multiple protected functional groups, are not suitable for selective reactions of complex polyol structures. We present a new ruthenium catalyst with a unique efficacy for the selective oxidation of a single hydroxyl group among many in unprotected polyol natural products. This oxidation enables the introduction of nitrogen-based functional groups into such structures that lack nitrogen atoms and enables a selective alcohol epimerization by stepwise or reversible oxidation and reduction.

  • Compound

    3-keto-andrographolide

  • Compound

    6-keto-aucubin

  • Compound

    3-keto-D-glucal

  • Compound

    15-keto-kirenol

  • Compound

    1-keto-ouabain

  • Compound

    3-keto-fusidic acid methyl ester

  • Compound

    3-keto-digoxigenin

  • Compound

    3-keto-cholic acid methyl ester

  • Compound

    1-keto-forskolin

  • Compound

    16-keto-estriol

  • Compound

    13-keto-mupirocin methyl ester

  • Compound

    7-epi-13-keto-deacetyl baccatin III

  • Compound

    13-keto-brefeldin A

  • Compound

    genipin lactone

  • Compound

    lagochirsine

  • Compound

    5-keto-ivermectin

  • Compound

    2,3-dihydro-1-keto-brefeldin A

  • Compound

    1-keto-oubagenin

  • Compound

    andrographolide-3-oxime

  • Compound

    andrographolide isoxazole

  • Compound

    andrographolide lactam

  • Compound

    dehydroxymethyl-andrographolide

  • Compound

    3-(N-phenyl)amino-dehydroxymethyl-andrographolide

  • Compound

    fusidic lactam methyl ester A

  • Compound

    fusidic lactam methyl ester B

  • Compound

    3-amino-fusidic acid methyl ester

  • Compound

    1,2-dihydro-3-(N-2,6-difluorophenyl)amino-D-glucal

  • Compound

    1,2-dihydro-3-(N-lithocholic)amino-D-glucal

  • Compound

    estriol lactol

  • Compound

    estriol lactam

  • Compound

    estriol N-phenyl-lactam

  • Compound

    3-epi-fusidic acid methyl ester

  • Compound

    1-epi-ouabain

  • Compound

    [Ru2(Cl)3(PPh2Me)6][Cl]

  • Compound

    [Ru2Cl3(PEt3)6][Cl]

  • Compound

    [Ru2Cl3(PEt2(p-Me2N-Ph))6][Cl]

  • Compound

    [Ru2(OTf)3(PPh2Me)6][OTf]

  • Compound

    [Ru2(OTf)3(PEt3)6][OTf]

  • Compound

    [Ru2(OTf)3(PEt2(p-Me2N-Ph))6][OTf]

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Acknowledgements

We thank the NIH (GM-55382) and the Berkeley Center for Green Chemistry Systems Approach to Green Energy Integrated Graduate Education and Research Traineeship for financial support. We acknowledge A. DiPasquale for assistance with X-ray crystallographic characterizations and the NIH (SIG S10-RR027172) for facility funding.

Author information

Affiliations

  1. Department of Chemistry, University of California, Berkeley, California 94720, USA

    • Christopher K. Hill
    •  & John F. Hartwig

Authors

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Contributions

C.K.H. and J.F.H. conceived and designed the experiments. C.K.H. performed the experiments. C.K.H. and J.F.H. analysed the data. C.K.H. and J.F.H. co-wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to John F. Hartwig.

Supplementary information

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Crystallographic information files

  1. 1.

    Supplementary information

    Crystallographic data for compound 1l

  2. 2.

    Supplementary information

    Crystallographic data for compound 2c

  3. 3.

    Supplementary information

    Crystallographic data for compound 2d

  4. 4.

    Supplementary information

    Crystallographic data for compound 2e

  5. 5.

    Supplementary information

    Crystallographic data for compound Ru-2-DABIII-Alkoxid

  6. 6.

    Supplementary information

    Crystallographic data for compound Ru-2

  7. 7.

    Supplementary information

    Crystallographic data for compound Ru-3-Cl