Abstract
Carbohydrates are an abundant, inexpensive and renewable biomass feedstock that could be a cornerstone for sustainable chemical manufacturing, but scalable and environmentally friendly methods that leverage these feedstocks are lacking. For example, 1-allyl sorbitol is the foundational building block for the polypropylene clarifying agent Millad NX 8000, which is produced on the multi-metric ton scale annually, but the manufacturing process at present requires superstoichiometric amounts of tin1,2. The NX 8000 additives dominate about 80% of the global clarified polypropylene market3 and are used in concentrations of 0.01–1% during polypropylene production to improve its transparency and resistance to high temperatures, translating to 300–30,000 metric tons annually. The market volume of polypropylene in 2022 was approximately 79.01 million metric tons (MMT), with demand expected to rise by nearly 33% to 105 MMT by 2030 (ref. 4). The cost and sustainability benefits of clarified polypropylene are driving this demand, necessitating more clarifying agents5. Here we report a high-yielding allylation of unprotected carbohydrates in water using a catalytic amount of indium metal and either allylboronic acid or the pinacol ester (allylBpin) as donors. Aldohexoses, aminohexoses, ketohexoses and aldopentoses are all allylated in high yield under mild conditions and the indium metal is recoverable and reusable with no loss of catalytic activity. Leveraging these features, this process was translated to a scalable continuous synthesis of 1-allyl sorbitol in flow6 with high yield and productivity through Bayesian optimization of reaction parameters.
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Data availability
All experimental and spectroscopic data are available in the paper and Supplementary Information.
Code availability
The code for the Bayesian optimization presented in this paper is available at GitHub (https://github.com/fflorit/Millad).
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Acknowledgements
We thank the technical support teams of NMR, mass spectrometry and microanalytical laboratories of the University of Illinois at Urbana-Champaign and Massachusetts Institute of Technology. This work was also supported by the Molecule Maker Lab Institute: an AI Research Institutes programme supported by the US National Science Foundation under grant no. CHE 2019897. We are also grateful to the National Institutes of Health (GM R35 127010) for generous financial support.
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T.A. conceived and contributed to the allylBpin reaction and flow chemistry, including experimental analytical setup, reaction development, DOE design, data analysis, product characterization and manuscript writing. T.M. and M.A. contributed to the allylBF3K reaction, including experimental analytical setup, reaction development, data analysis, product characterization and manuscript writing. M.D.B. discussed the results, provided suggestions, supervised and revised the paper. F.F. developed the Bayesian algorithm to flow and contributed to writing the paper. K.F.J. supervised the flow chemistry and revised the paper. S.E.D. conceptualized, supervised the project and revised the paper. All authors contributed to assembling the final draft of the paper.
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T.A., T.M., M.A., F.F., M.D.B., K.F.J. and S.E.D. are inventors on a patent application related to this work (US patent application no. 63/737,683) filed by the University of Illinois at Urbana-Champaign.
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Adak, T., Menard, T., Albritton, M. et al. Catalytic allylation of native hexoses and pentoses in water with indium. Nature 640, 94–99 (2025). https://doi.org/10.1038/s41586-025-08690-z
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DOI: https://doi.org/10.1038/s41586-025-08690-z
