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Merging allylic carbon–hydrogen and selective carbon–carbon bond activation

Abstract

Since the nineteenth century, many synthetic organic chemists have focused on developing new strategies to regio-, diastereo- and enantioselectively build carbon–carbon and carbon–heteroatom bonds in a predictable and efficient manner1,2,3. Ideal syntheses should use the least number of synthetic steps, with few or no functional group transformations and by-products, and maximum atom efficiency. One potentially attractive method for the synthesis of molecular skeletons that are difficult to prepare would be through the selective activation of C–H and C–C bonds4,5,6,7,8, instead of the conventional construction of new C–C bonds. Here we present an approach that exploits the multifold reactivity of easily accessible substrates9 with a single organometallic species to furnish complex molecular scaffolds through the merging of otherwise difficult transformations: allylic C–H and selective C–C bond activations10,11,12. The resulting bifunctional nucleophilic species, all of which have an all-carbon quaternary stereogenic centre, can then be selectively derivatized by the addition of two different electrophiles to obtain more complex molecular architecture from these easily available starting materials.

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Figure 1: General approach combining allylic C–H and selective C–C bond activation towards functionalized adducts.
Figure 2: Zirconocene-promoted allylic C–H and C–C bond activation of ω-ene-cyclopropanes.
Figure 3: Zirconocene-promoted allylic C–H and C–C bond activation of alkylidenecyclopropanes.
Figure 4: Merging allylic C–H activation and fragmentation en route to non-conjugated dienes.

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Acknowledgements

This research was supported by the Niedersachsen-Technion Research Cooperation Program, by the Israel Science Foundation administrated by the Israel Academy of Sciences and Humanities (140/12) and by the European Research Council under the European Community’s Seventh Framework Programme (ERC grant agreement no. 338912). I.M. is holder of the Sir Michael and Lady Sobell Academic Chair.

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A.M., D.D., T.Z., M.S., L.A. and I.M. planned, conducted and analysed experiments. I.M. had the idea for and directed the project, and wrote the manuscript with contributions from A.M. and D.D. All authors contributed to discussions.

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Correspondence to Ilan Marek.

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The authors declare no competing financial interests.

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Masarwa, A., Didier, D., Zabrodski, T. et al. Merging allylic carbon–hydrogen and selective carbon–carbon bond activation. Nature 505, 199–203 (2014). https://doi.org/10.1038/nature12761

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