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Efficient and stereodivergent synthesis of unsaturated acyclic fragments bearing contiguous stereogenic elements

Nature Chemistryvolume 10pages11641170 (2018) | Download Citation

Abstract

Synthetic organic strategies that enable the catalytic and rapid assembly of a large array of organic compounds that possess multiple stereocentres in acyclic systems are somewhat rare, especially when it comes to reaching today’s high standards of efficiency and selectivity. In particular, the catalytic preparation of a three-dimensional molecular layout of a simple acyclic hydrocarbon skeleton that possesses several stereocentres from simple and readily available reagents still represents a vastly uncharted domain. Here we report a rapid, modular, stereodivergent and diversity-oriented unified strategy to construct acyclic molecular frameworks that bear up to four contiguous and congested stereogenic elements, with remarkably high levels of stereocontrol and in only three catalytic steps from commercially available alkynes. A regio- and diastereoselective catalytic Heck migratory insertion reaction of alkenylcyclopropyl carbinols that merges selective C–C bond cleavage of a cyclopropane represents the key step.

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Acknowledgements

This research was supported by the Israel Science Foundation administrated by the Israel Academy of Sciences and Humanities (330/17) and by the European Research Council under the European Community’s Seventh Framework Program (ERC grant agreement no. 338912). I.M. is holder of the Sir Michael and Lady Sobell Academic Chair.

Author information

Author notes

  1. These authors contributed equally to this work: Jeffrey Bruffaerts, David Pierrot.

Affiliations

  1. The Mallat Family Laboratory of Organic Chemistry, Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, Israel

    • Jeffrey Bruffaerts
    • , David Pierrot
    •  & Ilan Marek

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Contributions

J.B., D.P. and I.M. planned the research. J.B. and D.P. conducted and analysed experiments. I.M. directed the project, and wrote the manuscript with contributions from J.B. and D.P. All the authors discussed the results and commented on the manuscript.

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Ilan Marek.

Supplementary information

  1. Supplementary Information

    Detailed experimental procedures with full descriptions of all molecules and complete NMR data of all new compounds

  2. Crystallographic data

    CIF for compound 6a; CCDC reference: 1813305

  3. Crystallographic data

    CIF for compound 6b; CCDC reference: 1813312

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DOI

https://doi.org/10.1038/s41557-018-0123-7

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