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Modular alkene synthesis from carboxylic acids, alcohols and alkanes via integrated photocatalysis

Nature Chemistry volume 16, pages 1822–1830 (2024)Cite this article

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Abstract

Alkenes serve as versatile building blocks in diverse organic transformations. Despite notable advancements in olefination methods, a general strategy for the direct conversion of carboxylic acids, alcohols and alkanes into alkenes remains a formidable challenge owing to their inherent reactivity disparities. Here we demonstrate an integrated photochemical strategy that facilitates a one-pot conversion of these fundamental building blocks into alkenes through a sequential C(sp3)–C(sp3) bond formation–fragmentation process, utilizing an easily accessible and recyclable phenyl vinyl ketone as the ‘olefination reagent’. This practical method not only offers an unparalleled paradigm for accessing value-added alkenes from abundant and inexpensive starting materials but also showcases its versatility through various complex scenarios, including late-stage on-demand olefination of multifunctional molecules, chain homologation of acids and concise syntheses of bioactive molecules. Moreover, initiating from carboxylic acids, alcohols and alkanes, this protocol presents a complementary approach to traditional olefination methods, making it a highly valuable addition to the research toolkit for alkene synthesis.

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Fig. 1: Synthesis of alkenes from diverse building blocks.
Fig. 2: The on-demand site-selective olefination of complex molecules bearing multiple functionalities.
Fig. 3: Synthetic applications.

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Data availability

The authors declare that all the data supporting the findings of this study are available within the article and its Supplementary Information.

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Acknowledgements

We thank the National Research Foundation, the Prime Minister’s Office of Singapore under its NRF-CRP programme (award NRFCRP25-2020RS-0002), the Ministry of Education (MOE) of Singapore (MOET2EP10120-0014 and MOET2EP10121-0004), NUS (Suzhou) Research Institute, National Natural Science Foundation of China (grant nos. 22071170 and 92156025) and the National Key Research and Development Program of China (2019YFA0905100) for the financial support provided. We thank H. Ting Ang (NUS), M. Wai Liaw (NUS) and H. Cao (University of Basel) for their valuable proofreading assistance on the manuscript.

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Authors and Affiliations

  1. Joint School of National University of Singapore and Tianjin University, International Campus of Tianjin University, Binhai New City, P. R. China

    Hao Zeng, Yu Zhao, Jun-An Ma & Jie Wu

  2. Department of Chemistry, National University of Singapore, Singapore, Republic of Singapore

    Hao Zeng, Ruize Yin, Yu Zhao & Jie Wu

  3. Department of Chemistry, Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Frontiers Science Center for Synthetic Biology (Ministry of Education) and Tianjin Collaborative Innovation Centre of Chemical Science and Engineering, Tianjin University, Tianjin, P. R. China

    Jun-An Ma

  4. National University of Singapore (Suzhou) Research Institute, Suzhou, P. R. China

    Jie Wu

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Contributions

H.Z., J.-A.M., Y.Z. and J.W. designed and analysed the experiments. H.Z. and R.Y. conducted the experiments. H.Z., J.-A.M., Y.Z. and J.W. wrote the manuscript. J.W. guided the whole project.

Corresponding authors

Correspondence to Yu Zhao, Jun-An Ma or Jie Wu.

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Nature Chemistry thanks Zhiwei Zuo and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary Information

Supplementary Figs. 1–22, Tables 1–13, Materials and methods, Experimental procedures, Mechanistic studies, Characterization data, Substrate limitation and extension and NMR spectra.

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Zeng, H., Yin, R., Zhao, Y. et al. Modular alkene synthesis from carboxylic acids, alcohols and alkanes via integrated photocatalysis. Nat. Chem. 16, 1822–1830 (2024). https://doi.org/10.1038/s41557-024-01642-6

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