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A unique approach to aldol products for the creation of all-carbon quaternary stereocentres

Nature Chemistry volume 1, pages 128–132 (2009)Cite this article

Abstract

Among the challenges facing asymmetric synthesis the selective construction of quaternary stereogenic centres, particularly those bearing all-carbon substituents, stands out. The aldol reaction has the potential to create such stereocentres, but, despite the many advances in this field, a highly selective and efficient procedure has remained elusive. Here we show that, by choosing an alternative retrosynthetic approach, such products can be prepared in a highly selective fashion. Through the consecutive addition of several organometallic derivatives, an allylzinc reagent is prepared and, on addition to an aldehyde, an aldol-type product is created. The one-pot operation involves the construction of three new carbon–carbon bonds and the formation of an all-carbon quaternary stereocentre. The products of the reaction are amenable to downstream modification, and the procedure should find applications in the fields of natural product synthesis and drug discovery.

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Figure 1: Common strategies for preparing enantiomerically enriched all-carbon quaternary stereocentres.
Figure 2: Alternative retrosynthetic analysis for the formation of aldol-type products.
Figure 3: Diastereoselective formation of aldol surrogates.
Figure 4: X-ray crystal structure determination of absolute configuration.
Figure 5: Conversion of the aldol surrogate to the target aldol derivative.

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Acknowledgements

This research was supported by the Israel Science Foundation administered by the Israel Academy of Sciences and Humanities (70/08) and by the Fund for promotion of Research at the Technion. The authors thank Mark Botoshansky for X-ray diffraction analyses. I.M. is holder of the Sir Michael and Lady Sobell Academic Chair.

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Authors and Affiliations

  1. The Mallat Family Laboratory of Organic Chemistry, Schulich Faculty of Chemistry and the Lise Meitner–Minerva Center for Computational Quantum Chemistry, Technion–Israel Institute of Technology, Haifa, 32000, Israel

    Jaya Prakash Das, Helena Chechik & Ilan Marek

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  1. Jaya Prakash Das
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  2. Helena Chechik
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  3. Ilan Marek
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Contributions

J.P.D. and H.C. planned, conducted and analysed the experiments. I.M. designed and directed the project and wrote the manuscript, with contributions from J.P.D. and H.C. All authors contributed to discussions.

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Correspondence to Ilan Marek.

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Crystallographic data for compound (R,S,S)-10a (CIF 22 kb)

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Crystallographic data for compound (S,S,S)-10a (CIF 20 kb)

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Das, J., Chechik, H. & Marek, I. A unique approach to aldol products for the creation of all-carbon quaternary stereocentres. Nature Chem 1, 128–132 (2009). https://doi.org/10.1038/nchem.131

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