Abstract
In drug discovery processes, changing the core structures of lead compounds to a variety of other ring systems is often needed, which typically requires laborious de novo syntheses of individual analogues. Here we report a conceptually different approach that allows rapid access to diverse core structures from a common intermediate using 1,2-oxaborines as a versatile molecular platform. A soft enolization/6π-electrocyclization strategy has been developed to efficiently synthesize 1,2-oxaborines from readily available enones or enals. Taking advantage of their multifaceted reactivities, 1,2-oxaborines can undergo further C−H functionalization and be transformed into a diverse range of arenes, heteroarenes and non-aromatic heterocycles. Finally, late-stage preparations of a suite of analogues that contain Lipitor substituents but with different aromatic cores are demonstrated using the 1,2-oxaborine-based core diversification strategy.
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Data availability
All the data generated or analysed during this study are included in this Article and its Supplementary Information. Crystallographic data for the structure of 3ja reported in this study has been deposited at the Cambridge Crystallographic Data Centre (CCDC), under deposition number 2409545. Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures.
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Acknowledgements
The University of Chicago is acknowledged for research support. We thank A. S. Filatov (University of Chicago) and X. Liu (University of Chicago) for X-ray crystallography. K. Wen (University of Chicago) is thanked for checking the experimental procedure.
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G.D. and Y.G. conceived and designed the experiments. Y.G., Q.Z and Y.Z. performed the experiments and analysed the data. Y.G. and G.D. prepared the paper together. G.D. directed the research.
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Nature Chemistry thanks Adam Noble, Qiuling Song and Tülay Yıldız for their contribution to the peer review of this work.
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Ge, Y., Zhu, Q., Zhu, Y. et al. Core diversification using 1,2-oxaborines as a versatile molecular platform. Nat. Chem. (2025). https://doi.org/10.1038/s41557-025-01971-0
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DOI: https://doi.org/10.1038/s41557-025-01971-0
