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Direct enantio-convergent transformation of racemic substrates without racemization or symmetrization

Nature Chemistry volume 2, pages 972–976 (2010)Cite this article

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Abstract

Asymmetric reactions that transform racemic mixtures into enantio-enriched products are in high demand, but classical kinetic resolution produces enantiopure compounds in <50% yield even in an ideal case. Many deracemization processes have thus been developed including dynamic kinetic resolution and dynamic kinetic asymmetric transformation, which can provide enantio-enriched products even after complete conversion of the racemic starting materials. However, these dynamic processes require racemization or symmetrization of the substrates or intermediates. We demonstrate a direct chemical enantio-convergent transformation without a racemization or symmetrization process. Copper(I)-catalysed asymmetric allylic substitution of a racemic allylic ether afforded a single enantiomer of an α-chiral allylboronate with complete conversion and high enantioselectivity (up to 98% enantiomeric excess). One enantiomer of the substrate undergoes an anti-SN2′-type reaction whereas the other enantiomer reacts via a syn-SN2′ pathway. The products, which cannot be prepared by dynamic procedures, have been used to construct all-carbon quaternary stereocentres.

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Figure 1: Conceptual schemes for asymmetric reactions of racemic chiral substrates for production of enantio-enriched compounds.
Figure 2: Experimental studies and plausible schematic explanations on the mechanism of the direct enantio-convergent transformation.
Figure 3: Synthesis of enantio-enriched homoallylic alcohols with an all-carbon quaternary or tertiary stereocentre.

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Acknowledgements

This work was supported by a Grant-in-Aid for Scientific Research (B) (JSPS) and the PRESTO program (JST). We thank T. Inabe for his assistance in X-ray analysis. Nippon Chemical Industrial is acknowledged for a gift of (R,R)-QuinoxP*. We also acknowledge DAICEL chemical industries for their help on the optical resolution of some starting materials.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo, 060-0810, Japan

    Hajime Ito, Shun Kunii & Masaya Sawamura

  2. PRESTO, Japan Science and Technology Agency (JST), Honcho, Kawaguchi, 332-0012, Saitama, Japan

    Hajime Ito

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  1. Hajime Ito
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  2. Shun Kunii
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Contributions

H.I. directed this study. Experiments were carried out by S.K. and H.I. Density functional theory calculations (Supplementary Information) were carried out by H.I. M.S. gave comments on the reaction mechanism and the preparation of the enantio-enriched starting materials.

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Correspondence to Hajime Ito.

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Supplementary information (PDF 3588 kb)

Supplementary information

nchem.801-S2.cif Crystallographic data for racemiccompound 6ea (CIF 18 kb)

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Ito, H., Kunii, S. & Sawamura, M. Direct enantio-convergent transformation of racemic substrates without racemization or symmetrization. Nature Chem 2, 972–976 (2010). https://doi.org/10.1038/nchem.801

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