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Carbonyl cross-metathesis via deoxygenative gem-di-metal catalysis

Nature Chemistry volume 16, pages 107–113 (2024)Cite this article

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Abstract

Carbonyls and alkenes are versatile functional groups, whose reactivities are cornerstones of organic synthesis. The selective combination of two carbonyls to form an alkene—a carbonyl cross-metathesis—would be a valuable tool for their exchange. Yet, this important synthetic challenge remains unsolved. Although alkene/alkene and alkene/carbonyl cross-metathesis reactions are known, there is a lack of analogous methods for deoxygenative cross-coupling of two carbonyl compounds. Here we report a pair of strategies for the cross-metathesis of unbiased carbonyls, allowing an aldehyde to be chemo- and stereoselectively combined with another aldehyde or ketone. These mild, catalytic methods are promoted by earth-abundant metal salts and enable rapid access to an unprecedentedly broad range of either Z- or E-alkenes by two distinct mechanisms—entailing transiently generated (1) carbenes and ylides (via Fe catalysis) or (2) doubly nucleophilic gem-di-metallics (via Cr catalysis).

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Fig. 1: Carbonyl metathesis strategies are rare, and cross-selectivity mechanisms must be developed.
Fig. 2: The Cr-catalysed carbonyl metathesis has wide scope with robust E- and cross-selectivity.
Fig. 3: Cross-metathesis: selectivity probes and mechanism.

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Data availability

The data supporting the findings of this study are included in Supplementary Information.

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Acknowledgements

We thank the National Institutes of Health (R35 GM119812), National Science Foundation (CAREER 1654656) and Brown Science Foundation (BIA) for funding (to D.A.N.), and we are grateful to T. Bednar for independent verification of the robustness of this method.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, USA

    Lumin Zhang & David A. Nagib

  2. Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China

    Lumin Zhang

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  1. Lumin Zhang
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L.Z. and D.A.N. designed these strategies and wrote the manuscript. L.Z. performed all experiments and analysis.

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Correspondence to Lumin Zhang or David A. Nagib.

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Zhang, L., Nagib, D.A. Carbonyl cross-metathesis via deoxygenative gem-di-metal catalysis. Nat. Chem. 16, 107–113 (2024). https://doi.org/10.1038/s41557-023-01333-8

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