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

Nature Chemistry volume 9, pages 1213–1221 (2017)Cite this article

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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.

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Figure 1: Model alcohol oxidation and catalyst synthesis.
Figure 2: Examples of the site-selective oxidation of polyol natural products.
Figure 3: Examples of the 1,3-eclipsing interactions that influence the selectivity of the dehydrogenation of certain polyols.
Figure 4: Oxidation and amination of structurally complex polyol natural products.
Figure 5: The reduction of complex ketones and one-step epimerization of complex alcohols.

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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.

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

    Christopher K. Hill & John F. Hartwig

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  1. Christopher K. Hill
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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.

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Correspondence to John F. Hartwig.

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The authors declare no competing financial interests.

Supplementary information

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Supplementary information (PDF 2520 kb)

Supplementary information

Crystallographic data for compound 1l (CIF 1908 kb)

Supplementary information

Crystallographic data for compound 2c (CIF 382 kb)

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Crystallographic data for compound 2d (CIF 406 kb)

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Crystallographic data for compound 2e (CIF 540 kb)

Supplementary information

Crystallographic data for compound Ru-2-DABIII-Alkoxid (CIF 2225 kb)

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Crystallographic data for compound Ru-2 (CIF 2846 kb)

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Crystallographic data for compound Ru-3-Cl (CIF 725 kb)

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Hill, C., Hartwig, J. Site-selective oxidation, amination and epimerization reactions of complex polyols enabled by transfer hydrogenation. Nature Chem 9, 1213–1221 (2017). https://doi.org/10.1038/nchem.2835

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