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. 2024 Apr 5;26(13):2612-2616.
doi: 10.1021/acs.orglett.4c00624. Epub 2024 Mar 21.

Cascade Aryne Aminoarylation for Biaryl Phenol Synthesis

Aniruddha Das  1   2 , Danielle L Myers  1 , Venkataraman Ganesh  2 , Michael F Greaney  1
Affiliations

Cascade Aryne Aminoarylation for Biaryl Phenol Synthesis

Aniruddha Das et al. Org Lett. .

Abstract

We describe a transition metal-free approach to hindered 3-amino-2-aryl phenols through a cascade nucleophilic addition / Smiles-Truce rearrangement of a functionalized Kobayashi aryne precursor. Under anionic conditions, secondary alkyl amines add to the aryne intermediate to set up an aryl transfer from a neighboring sulfonate group. The use of a sulfonate, rather than the more typical sulfonamide, enables access to phenolic biaryl products that are important motifs in natural products and pharmaceuticals.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Aryne Approaches to Biaryls
Scheme 2
Scheme 2. Substrate Design and Prior Art
Scheme 3
Scheme 3. Substrate Scope for Nucleophiles
Scheme 4
Scheme 4. Substrate Scope for the Migratory Aryl Group
Scheme 5
Scheme 5. Synthetic Utility of Biaryl Phenols
See this image and copyright information in PMC

References

    1. Zhang Y.-F.; Shi Z.-J. Upgrading Cross-Coupling Reactions for Biaryl Syntheses. Acc. Chem. Res. 2019, 52, 161–169. 10.1021/acs.accounts.8b00408. - DOI - PubMed
    1. García-López J.-A.; Greaney M. F. Synthesis of Biaryls Using Aryne Intermediates. Chem. Soc. Rev. 2016, 45, 6766–6798. 10.1039/C6CS00220J. - DOI - PubMed

    1. Recent benzyne reviews:

    2. Fluegel L. L.; Hoye T. R. Hexadehydro-Diels–Alder Reaction: Benzyne Generation via Cycloisomerization of Tethered Triynes. Chem. Rev. 2021, 121, 2413–2444. 10.1021/acs.chemrev.0c00825. - DOI - PMC - PubMed
    3. Roy T.; Biju A. T. Recent Advances in Molecular Rearrangements Involving Aryne Intermediates. Chem. Commun. 2018, 54, 2580–2594. 10.1039/C7CC09122B. - DOI - PubMed
    4. Matsuzawa T.; Yoshida S.; Hosoya T. Recent Advances in Reactions between Arynes and Organosulfur Compounds. Tetrahedron Lett. 2018, 59, 4197–4208. 10.1016/j.tetlet.2018.10.031. - DOI
    5. Takikawa H.; Nishii A.; Sakai T.; Suzuki K. Aryne-Based Strategy in the Total Synthesis of Naturally Occurring Polycyclic Compounds. Chem. Soc. Rev. 2018, 47, 8030–8056. 10.1039/C8CS00350E. - DOI - PubMed
    1. Wittig G. Phenyl-lithium, der Schlüssel zu einer neuen Chemie metallorganischer Verbindungen. Naturwissenschaften 1942, 30, 696–703. 10.1007/BF01489519. - DOI
    1. Himeshima Y.; Sonoda T.; Kobayashi H. Fluoride-Induces 1,2-Elimination of O-Trimethylsilylphenyl Triflate to Benzyne under Mild Conditions. Chem. Lett. 1983, 12, 1211–1214. 10.1246/cl.1983.1211. - DOI

    2. Review:

    3. Shi J.; Li L.; Li Y. o-Silylaryl Triflates: A Journey of Kobayashi Aryne Precursors. Chem. Rev. 2021, 121, 3892–4044. 10.1021/acs.chemrev.0c01011. - DOI - PubMed