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. 2020 Oct 2;10(19):11365-11370.
doi: 10.1021/acscatal.0c03423. Epub 2020 Sep 15.

trans-Selective and Switchable Arene Hydrogenation of Phenol Derivatives

Marco Wollenburg  1 , Arne Heusler  1 , Klaus Bergander  1 , Frank Glorius  1
Affiliations

trans-Selective and Switchable Arene Hydrogenation of Phenol Derivatives

Marco Wollenburg et al. ACS Catal. .

Abstract

A trans-selective arene hydrogenation of abundant phenol derivatives catalyzed by a commercially available heterogeneous palladium catalyst is reported. The described method tolerates a variety of functional groups and provides access to a broad scope of trans-configurated cyclohexanols as potential building blocks for life sciences and beyond in a one-step procedure. The transformation is strategically important because arene hydrogenation preferentially delivers the opposite cis-isomers. The diastereoselectivity of the phenol hydrogenation can be switched to the cis-isomers by employing rhodium-based catalysts. Moreover, a protocol for the chemoselective hydrogenation of phenols to cyclohexanones was developed.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Diastereoselectivity in the Process of Arene Hydrogenation and Switchable (Stereo)selectivity in the Hydrogenation of Phenols
Scheme 2
Scheme 2. Substrate Scope for the trans-Selective Hydrogenation of Phenols
Combined yields of isolated product after column chromatography are given. The d.r. values were determined by GC-MS or 1H NMR analysis prior to purification. Piperidines and amines were trapped with Boc2O prior to isolation. For details, see Supporting Information. 48 h. iPrOH as solvent. K2CO3 as additive. The ratio is trans/trans:trans/cis:cis/cis.
Scheme 3
Scheme 3. Substrate Scope for the cis-Selective Hydrogenation of Phenols
Combined yields of isolated product after column chromatography are given. The d.r. values were determined by GC-MS or 1H NMR analysis prior to purification. Piperidines were trapped with Boc2O prior to isolation. For details, see Supporting Information. CAAC = cyclic (alkyl)(amino)carbene. Dipp = 2,6-diisopropylphenyl. [Rh(COD)Cl]2 (2 mol %). 5 wt % Pd/Al2O3 (4 mol %). 48 h. H2 (50 bar). H2 (20 bar). iPrOH as solvent.
Scheme 4
Scheme 4. Substrate Scope for the Ketone-Selective Hydrogenation of Phenols
Yields of isolated product after column chromatography are given. DCE = 1,2-dichloroethane.
Scheme 5
Scheme 5. Substitution Pattern and Diastereoselectivity for the Hydrogenation of Phenols
Combined yields of isolated product after column chromatography are given. Diastereoselectivity and yields in parentheses were determined by 1H NMR analysis. For details, see Supporting Information. H2 (10 bar). Yield determined by GC-FID analysis.
Scheme 6
Scheme 6. Synthetic Applications of trans-Cyclohexanols
For experimental details, see Supporting Information.
See this image and copyright information in PMC

References

    1. For reviews on arene hydrogenation, see:

    2. Wiesenfeldt M. P.; Nairoukh Z.; Dalton T.; Glorius F. Selective Arene Hydrogenation for Direct Access to Saturated Carbo- and Heterocycles. Angew. Chem., Int. Ed. 2019, 58, 10460.10.1002/anie.201814471. - DOI - PMC - PubMed
    3. Giustra Z. X.; Ishibashi J. S. A.; Liu S.-Y. Homogeneous Metal Catalysis for Conversion between Aromatic and Saturated Compounds. Coord. Chem. Rev. 2016, 314, 134.10.1016/j.ccr.2015.11.006. - DOI
    4. Gualandi A.; Savoia D. Substrate Induced Diastereoselective Hydrogenation/Reduction of Arenes and Heteroarenes. RSC Adv. 2016, 6, 18419.10.1039/C5RA23908G. - DOI
    5. Qi S.-C.; Wei X.-Y.; Zong Z.-M.; Wang Y.-K. Application of Supported Metallic Catalysts in Catalytic Hydrogenation of Arenes. RSC Adv. 2013, 3, 14219.10.1039/c3ra40848e. - DOI
    6. Gual A.; Godard C.; Castillón S.; Claver C. Soluble Transition-Metal Nanoparticles-Catalysed Hydrogenation of Arenes. Dalton Trans. 2010, 39, 11499.10.1039/c0dt00584c. - DOI - PubMed

    7. Soluble Transition-Metal Nanoparticles-Catalysed Hydrogenation of Arenes. For books on arene hydrogenation, see:

    8. Foubelo F.; Yus M.. Arene Chemistry: Reaction Mechanisms and Methods for Aromatic Compounds; Mortier J., Ed.; Wiley: Hoboken, 2016; p 337.
    9. Bianchini C.; Meli A.; Vizza F.. The Handbook of Homogeneous Hydrogenation; de Vries J. G.; Elsevier C. J., Eds.; Wiley-VCH: Weinheim, 2006; p 455.
    10. Nishimura S.Handbook of Heterogeneous Catalytic Hydrogenation for Organic Synthesis; John Wiley & Sons: New York, 2001; p 414.

    11. For selected reviews on the more general dearomatization of arenes, see:

    12. Wertjes W. C.; Southgate E. H.; Sarlah D. Recent Advances in Chemical Dearomatization of Nonactivated Arenes. Chem. Soc. Rev. 2018, 47, 7996.10.1039/C8CS00389K. - DOI - PubMed
    13. Huck C. J.; Sarlah D. Shaping Molecular Landscapes: Recent Advances, Opportunities, and Challenges in Dearomatization. Chem. 2020, 6, 1589.10.1016/j.chempr.2020.06.015. - DOI - PMC - PubMed
    14. You S.-L., Ed., Asymmetric Dearomatization Reactions; Wiley-VCH: Weinheim, 2016.
    1. Weissermel K.; Arpe H.-J.. Industrial Organic Chemistry; Wiley-VCH: Weinheim, 2008; p 337.
    1. Foppa L.; Dupont J. Benzene Partial Hydrogenation: Advances and Perspectives. Chem. Soc. Rev. 2015, 44, 1886.10.1039/C4CS00324A. - DOI - PubMed
    2. Nagahara H.; Ono M.; Konishi M.; Fukuoka Y. Partial Hydrogenation of Benzene to Cyclohexene. Appl. Surf. Sci. 1997, 121–122, 448.10.1016/S0169-4332(97)00325-5. - DOI
    1. Wiesenfeldt M. P.; Nairoukh Z.; Li W.; Glorius F. Hydrogenation of Fluoroarenes: Direct Access to all-cis-(Multi)fluorinated Cycloalkanes. Science 2017, 357, 908.10.1126/science.aao0270. - DOI - PubMed
    2. Nairoukh Z.; Wollenburg M.; Schlepphorst C.; Bergander K.; Glorius F. The Formation of all-cis-(Multi)fluorinated Piperidines by a Dearomatization–Hydrogenation Process. Nat. Chem. 2019, 11, 264.10.1038/s41557-018-0197-2. - DOI - PMC - PubMed
    3. Zhang X.; Ling L.; Luo M.; Zeng X. Accessing Difluoromethylated and Trifluoromethylated cis-Cycloalkanes and Saturated Heterocycles: Preferential Hydrogen Addition to the Substitution Sites for Dearomatization. Angew. Chem., Int. Ed. 2019, 58, 16785.10.1002/anie.201907457. - DOI - PubMed
    4. Wollenburg M.; Moock D.; Glorius F. Hydrogenation of Borylated Arenes. Angew. Chem., Int. Ed. 2019, 58, 6549.10.1002/anie.201810714. - DOI - PubMed
    5. Ling L.; He Y.; Zhang X.; Luo M.; Zeng X. Hydrogenation of (Hetero)aryl Boronate Esters with a Cyclic (Alkyl)(amino)carbene–Rhodium Complex: Direct Access to cis-Substituted Borylated Cycloalkanes and Saturated Heterocycles. Angew. Chem., Int. Ed. 2019, 58, 6554.10.1002/anie.201811210. - DOI - PubMed
    6. Wiesenfeldt M. P.; Knecht T.; Schlepphorst C.; Glorius F. Silylarene Hydrogenation: A Strategic Approach that Enables Direct Access to Versatile Silylated Saturated Carbo- and Heterocycles. Angew. Chem., Int. Ed. 2018, 57, 8297.10.1002/anie.201804124. - DOI - PubMed
    7. Wei Y.; Rao B.; Cong X.; Zeng X. Highly Selective Hydrogenation of Aromatic Ketones and Phenols Enabled by Cyclic (Amino)(alkyl)carbene Rhodium Complexes. J. Am. Chem. Soc. 2015, 137, 9250.10.1021/jacs.5b05868. - DOI - PubMed
    1. For reviews on enantioselective hydrogenation of (hetero)arenes, see:Zhao D.; Candish L.; Paul D.; Glorius F.. N-Heterocyclic Carbenes in Asymmetric Hydrogenation. ACS Catal. 2016, 6, 5978.
    2. He Y.-M.; Song F.-T.; Fan Q.-H. Advances in Transition Metal-Catalyzed Asymmetric Hydrogenation of Heteroaromatic Compounds. Top. Curr. Chem. 2013, 343, 145.10.1007/128_2013_480. - DOI - PubMed
    3. Wang D.-S.; Chen Q.-A.; Lu S.-M.; Zhou Y.-G. Asymmetric Hydrogenation of Heteroarenes and Arenes. Chem. Rev. 2012, 112, 2557.10.1021/cr200328h. - DOI - PubMed
    4. Glorius F. Asymmetric Hydrogenation of Aromatic Compounds. Org. Biomol. Chem. 2005, 3, 4171.10.1039/b512139f. - DOI - PubMed