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Visible light-driven conjunctive olefination

Nature Chemistry volume 14, pages 66–70 (2022)Cite this article

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A Publisher Correction to this article was published on 26 November 2021

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Abstract

Carboxylic acids and aldehydes are ubiquitous in chemistry and are native functionalities in many bioactive molecules and natural products. As such, a general cross-coupling process that involves these partners would open new avenues to achieve molecular diversity. Here we report a visible-light-mediated and transition metal-free conjunctive olefination that uses an alkene ‘linchpin’ with a defined geometry to cross-couple complex molecular scaffolds that contain carboxylic acids and aldehydes. The chemistry merges two cornerstones of organic synthesis—namely, the Wittig reaction and photoredox catalysis—in a catalytic cycle that couples a radical addition process with the redox generation of a phosphonium ylide. The methodology allows the rapid structural diversification of bioactive molecules and natural products in a native form, with a high functional group tolerance, and also forges a new alkene functional group with a programmable E–Z stereochemistry.

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Fig. 1: Conceptual design of the process.
Fig. 2: Scale-up studies and experiments for mechanistic insights.

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The data supporting the findings of this study are available within the paper and its Supplementary Information.

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Acknowledgements

We thank the EPSRC for funding (New Investigator Award EP/V006401/1 to M.S.). M.S. thanks the University of Nottingham and the Green Chemicals Beacon of Excellence for a Nottingham Research Fellowship. D.F. thanks the School of Chemistry, University of Nottingham, for a doctoral fellowship. We thank R. Denton and P. Melchiorre for stimulating discussions and M. Piccinno for proofreading this manuscript.

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Authors and Affiliations

  1. GSK Carbon Neutral Laboratories for Sustainable Chemistry, University of Nottingham, Nottingham, UK

    Dario Filippini & Mattia Silvi

  2. School of Chemistry, University of Nottingham, Nottingham, UK

    Dario Filippini & Mattia Silvi

Authors
  1. Dario Filippini
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  2. Mattia Silvi
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Contributions

M.S. conceived and discovered the reactivity, led the project and prepared the manuscript with contributions from D.F. D.F. carried out most of the experimental work within the optimization studies and the exploration of the reaction scope.

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Correspondence to Mattia Silvi.

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The authors declare no competing interests.

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Peer review information Nature Chemistry thanks the anonymous reviewers for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

General experimental details; synthesis and characterization data for starting materials, catalysts and novel products; experimental details for mechanistic studies, bibliographic references, NMR spectra. The file is organized in Supplementary Sections 1–6 and includes Figs. 1–5.

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Filippini, D., Silvi, M. Visible light-driven conjunctive olefination. Nat. Chem. 14, 66–70 (2022). https://doi.org/10.1038/s41557-021-00807-x

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