Abstract
Arene- and heteroarene-fused rings are pervasive in biologically active molecules. Direct annulation between a C–H bond on the aromatic core and a tethered alkyl moiety provides a straightforward approach to access these scaffolds; however, such a strategy is often hampered by the need of special reactive groups and/or less compatible cyclization conditions. It would be synthetically appealing if a common native functional group can be used as a handle to enable a general C–H annulation with diverse aromatic rings. Here, we show a deacylative annulation strategy for preparing a large variety of aromatic-fused rings from linear simple ketone precursors. The reaction starts with homolytic cleavage of the ketone α C–C bond via a pre-aromatic intermediate, followed by a radical-mediated dehydrogenative cyclization. Using widely available ketones as the robust radical precursors, this deconstructive approach allows streamlined assembly of complex polycyclic structures with broad functional group tolerance.
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Details about materials and methods, experimental procedures and characterization data are available in the Supplementary Information. Additional data are available from the corresponding authors upon request.
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Acknowledgements
This work was supported by NIGMS (grant no. 2R01GM109054). X.Z. thanks the International Talent Training Project of Dalian Institute of Chemical Physics for financial support. Umicore AG & Co KG is acknowledged for a donation of Ir salts. We thank J. Wang for helpful discussions.
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X.Z, Y.X. and G.D. conceived and designed the experiments. X.Z. and Y.X. performed the experiments. X.Z., Y.X. and G.D. co-wrote the manuscript.
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Zhou, X., Xu, Y. & Dong, G. Deacylation-aided C–H alkylative annulation through C–C cleavage of unstrained ketones. Nat Catal 4, 703–710 (2021). https://doi.org/10.1038/s41929-021-00661-7
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DOI: https://doi.org/10.1038/s41929-021-00661-7
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