Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Feb 26;29(5):1012.
doi: 10.3390/molecules29051012.

Dearomatization of 3-Aminophenols for Synthesis of Spiro[chromane-3,1'-cyclohexane]-2',4'-dien-6'-ones via Hydride Transfer Strategy-Enabled [5+1] Annulations

Jia-Cheng Ge  1   2 , Yufeng Wang  1 , Feng-Wei Guo  1 , Xiangyun Kong  1 , Fangzhi Hu  1 , Shuai-Shuai Li  1   2
Affiliations

Dearomatization of 3-Aminophenols for Synthesis of Spiro[chromane-3,1'-cyclohexane]-2',4'-dien-6'-ones via Hydride Transfer Strategy-Enabled [5+1] Annulations

Jia-Cheng Ge et al. Molecules. .

Abstract

The Sc(OTf)3-catalyzed dearomative [5+1] annulations between readily available 3-aminophenols and O-alkyl ortho-oxybenzaldehydes were developed for synthesis of spiro[chromane-3,1'-cyclohexane]-2',4'-dien-6'-ones. The "two-birds-with-one-stone" strategy was disclosed by the dearomatization of phenols and direct α-C(sp3)-H bond functionalization of oxygen through cascade condensation/[1,5]-hydride transfer/dearomative-cyclization process. In addition, the antifungal activity assay and derivatizations of products were conducted to further enrich the utility of the structure.

Keywords: C(sp3)–H bond functionalization; antifungal activity; dearomatization; spiro[chromane-3,1′-cyclohexane]-2′,4′-dien-6′-ones.

PubMed Disclaimer

Conflict of interest statement

Jia-Cheng Ge and Shuai-Shuai Li were employed by the company Hailir Pesticides and Chemicals Group Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Scheme 1
Scheme 1
(a) Dearomatization of phenols. (b) Direct dearomatization of phenols. (c) The α-C(sp3)− H bond functionalization of amine. (d) The α-C(sp3)− H bond functionalization of oxygen. (e) In situ formed o-QM as hydride acceptor for achieving dearomatization of phenols and a-C(sp3)−H bond functionalization of oxygen. (f) Dearomative [5 + 1] annulation with O-alkyl ortho-oxybenzaldehyde as five-atom synthon.
Scheme 2
Scheme 2
The scope of O-alkyl ortho-oxybenzaldehydes for the dearomative [5+1] annulations. Reaction conditions: 1 (0.1 mmol), 2a (0.15 mmol), Sc(OTf)3 (20 mol%), TFE (1 mL), at 120 °C under air for 5 h; isolated yield after column chromatography; dr > 20:1, dr was determined by 1H NMR.
Scheme 3
Scheme 3
The substrate scope of the dearomative [5+1] annulations. Reaction conditions: 1 (0.1 mmol), 2 (0.15 mmol), Sc(OTf)3 (20 mol%), TFE (1 mL), at 120 °C under air for 5 h; isolated yield after column chromatography; dr > 20:1, dr was determined by 1H NMR.
Scheme 4
Scheme 4
(a) Gram-scale synthesis of products 3a and 3k. (b) Derivatization of Product 3k. (c) Synthesis of polyarylated methane 5a.
Scheme 5
Scheme 5
The investigation into the influence factor for the hydride transfer process.
Scheme 6
Scheme 6
Proposed mechanism.
See this image and copyright information in PMC

References

    1. Della Ca’ N., Fontana M., Motti E., Catellani M. Pd/Norbornene: A Winning Combination for Selective Aromatic Functionalization via C–H Bond Activation. Acc. Chem. Res. 2016;49:1389–1400. doi: 10.1021/acs.accounts.6b00165. - DOI - PubMed
    1. Wang J., Dong G. Palladium/Norbornene Cooperative Catalysis. Chem. Rev. 2019;119:7478–7528. doi: 10.1021/acs.chemrev.9b00079. - DOI - PMC - PubMed
    1. Luckemeier L., Pierau M., Glorius F. Asymmetric arene hydrogenation: Towards sustainability and application. Chem. Soc. Rev. 2023;52:4996–5012. doi: 10.1039/D3CS00329A. - DOI - PMC - PubMed
    1. Cheng Y.-Z., Feng Z., Zhang X., You S.-L. Visible-light induced dearomatization reactions. Chem. Soc. Rev. 2022;51:2145–2170. doi: 10.1039/C9CS00311H. - DOI - PubMed
    1. Xia Z.-L., Xu-Xu Q.-F., Zheng C., You S.-L. Chiral phosphoric acid-catalyzed asymmetric dearomatization reactions. Chem. Soc. Rev. 2020;49:286–300. doi: 10.1039/C8CS00436F. - DOI - PubMed

LinkOut - more resources