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Chemoselective oxidative generation of ortho-quinone methides and tandem transformations

Nature Chemistry volume 12, pages 353–362 (2020)Cite this article

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Abstract

ortho-Quinone methides are useful transient synthetic intermediates in organic synthesis. These species are most often generated in situ by the acid- or base-mediated transformation of phenols that have been pre-functionalized at a benzylic position, or by biomimetic oxidation of the corresponding ortho-alkylphenols with metal oxidants or transition-metal complexes. Here we describe a method for the transition-metal-free oxidative generation of o-QMs from ortho-alkylarenols, using hypoiodite catalysis under nearly neutral conditions, which can then be applied in one-pot tandem reactions. This method for the chemoselective oxidative generation of ortho-quinone methides may prove superior to previous methods with respect to environmental issues and scope, and can be applied to various tandem reactions such as inter- or intramolecular [4 + 2] cycloaddition, oxa-6π-electrocyclization, conjugate addition and spiroepoxidation.

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Fig. 1: Generation of o-QMs and synthetic application.
Fig. 2: Oxidative generation of o-QMs catalysed by ammonium hypoiodite.
Fig. 3: Inter- and intramolecular tandem oxidative [4 + 2] cycloaddition.
Fig. 4: Tandem oxidative conjugate addition.
Fig. 5: Oxidative spiroepoxidation of phenols.
Fig. 6: Reaction mechanism and enantioselective reactions.

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Data availability

All data generated and analysed during this study are included in this Article and its Supplementary Information. Crystallographic data for the structures reported in this Article have been deposited at the Cambridge Crystallographic Data Centre, under deposition numbers CCDC 1893878 (8a), 1893879 (10ia), 1893880 (14a) and 1893881 (19f). Copies of the data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif.

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Acknowledgements

Financial support for this project was partially provided by JSPS.KAKENHI (15H05755 (to K.I.), 15H05810 (to K.I.), 15H05484 (to M.U.), 18H01973 (to M.U.)), Inoue Research Award for Young Scientists (to M.U.), and the Program for Leading Graduate Schools: IGER Program in Green Natural Sciences (MEXT). We thank T. Yasui, K. Ohori, N. Sahara and O. Katade for their assistance during the initial investigations. We thank K. Nishimura for electrospray ionization-mass spectrometry analysis. We are grateful to the Kaneka Corporation and Mitsubishi Gas Chemical Co. for providing NaOCl·5H2O and 60 wt% H2O2, respectively.

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Authors and Affiliations

  1. Graduate School of Engineering, Nagoya University, Nagoya, Japan

    Muhammet Uyanik, Kohei Nishioka, Ryutaro Kondo & Kazuaki Ishihara

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Contributions

M.U. and K.I. developed the concept and conceived the experiments. K.N. and R.K. performed the experiments. K.N., R.K. and M.U. analysed the data. M.U. prepared the manuscript with assistance from K.I.

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Correspondence to Kazuaki Ishihara.

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Supplementary information

Supplementary Information

Experimental procedures, product characterization, X-ray crystallographic analysis and mechanistic studies.

Crystallographic data

Crystallographic data for compound 8a. CCDC reference 1893878.

Crystallographic data

Crystallographic data for compound 10ia. CCDC reference 1893879.

Crystallographic data

Crystallographic data for compound 14a. CCDC reference 1893880.

Crystallographic data

Structure factors file for compound 14a. CCDC reference 1893880.

Crystallographic data

Crystallographic data for compound 19f. CCDC reference 1893881.

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Uyanik, M., Nishioka, K., Kondo, R. et al. Chemoselective oxidative generation of ortho-quinone methides and tandem transformations. Nat. Chem. 12, 353–362 (2020). https://doi.org/10.1038/s41557-020-0433-4

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