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
. 2015 Jan 14;137(1):490-8.
doi: 10.1021/ja5116452. Epub 2014 Dec 24.

Cobalt(III)-catalyzed synthesis of indazoles and furans by C-H bond functionalization/addition/cyclization cascades

Joshua R Hummel  1 , Jonathan A Ellman
Affiliations

Cobalt(III)-catalyzed synthesis of indazoles and furans by C-H bond functionalization/addition/cyclization cascades

Joshua R Hummel et al. J Am Chem Soc. .

Abstract

The development of operationally straightforward and cost-effective routes for the assembly of heterocycles from simple inputs is important for many scientific endeavors, including pharmaceutical, agrochemical, and materials research. In this article we describe the development of a new air-stable cationic Co(III) catalyst for convergent, one-step benchtop syntheses of N-aryl-2H-indazoles and furans by C-H bond additions to aldehydes followed by in situ cyclization and aromatization. Only a substoichiometric amount of AcOH is required as an additive that is both low-cost and convenient to handle. The syntheses of these heterocycles are the first examples of Co(III)-catalyzed additions to aldehydes, and reactions are demonstrated for a variety of aromatic, heteroaromatic, and aliphatic derivatives. The syntheses of both N-aryl-2H-indazoles and furans have been performed on 20 mmol scales and should be readily applicable to larger scales. The reported heterocycle syntheses also demonstrate the use of directing groups that have not previously been applied to Co(III)-catalyzed C-H bond functionalizations. Additionally, the synthesis of furans demonstrates the first example of Co(III)-catalyzed functionalization of alkenyl C-H bonds.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Rhodium- and cobalt-catalyzed heterocycle synthesis via aldehyde addition followed by cyclative capture.
Scheme 1
Scheme 1. Synthesis of [Cp*Co(C6H6)][B(C6F5)4]2 (5)
Scheme 2
Scheme 2. Gram Scale Indazole and Furan Synthesis Using Catalyst 5
Scheme 3
Scheme 3. Azobenzene and Aldehyde Competition Experiments to Analyze Electronic Effects
Scheme 4
Scheme 4. Reversibility of Co(III)-Catalyzed C–H Functionalization Using Deuterated Azobenzenes
Scheme 5
Scheme 5. Reversibility of Co(III)-Catalyzed Aldehyde Insertion Using a Synthetic Intermediate
Scheme 6
Scheme 6. Proposed Mechanism of Co(III)-Catalyzed C–H Functionalization/Addition/Cyclization Cascade
See this image and copyright information in PMC

References

    1. For select recent reviews on C–H functionalization, see:

    2. Wencel-Delord J.; Glorius F. Nat. Chem. 2013, 5, 369. - PubMed
    3. Arockiam P. B.; Bruneau C.; Dixneuf P. H. Chem. Rev. 2012, 112, 5879. - PubMed
    4. Li B.-J.; Shi Z.-J. Chem. Soc. Rev. 2012, 41, 5588. - PubMed
    5. Yamaguchi J.; Yamaguchi A. D.; Itami K. Angew. Chem., Int. Ed. 2012, 51, 8960. - PubMed
    6. Engle K. M.; Mei T.-S.; Wasa M.; Yu J.-Q. Acc. Chem. Res. 2012, 45, 788. - PMC - PubMed
    7. Ackermann L. Chem. Rev. 2011, 111, 1315. - PubMed
    8. Cho S. H.; Kim J. Y.; Kwak J.; Chang S. Chem. Soc. Rev. 2011, 40, 5068. - PubMed
    9. Lyons T. W.; Sanford M. S. Chem. Rev. 2010, 110, 1147. - PMC - PubMed
    10. Mkhalid I. A. I.; Barnard J. H.; Marder T. B.; Murphy J. M.; Hartwig J. F. Chem. Rev. 2010, 110, 890. - PubMed
    11. Colby D. A.; Bergman R. G.; Ellman J. A. Chem. Rev. 2010, 110, 624. - PMC - PubMed
    12. Seregin I. V.; Gevorgyan V. Chem. Soc. Rev. 2007, 36, 1173. - PMC - PubMed

    1. For recent reviews on Rh(III)-catalyzed C–H functionalization, see:

    2. Song G.; Wang F.; Li X. Chem. Soc. Rev. 2012, 41, 3651. - PubMed
    3. Patureau F. W.; Wencel-Delord J.; Glorius F. Aldrichimica Acta 2012, 45, 31.
    4. Satoh T.; Miura M. Chem.—Eur. J. 2010, 16, 11212. - PubMed

    1. For reviews on C–H bond additions to polarized π bonds, see:

    2. Zhang X.-S.; Chen K.; Shi Z.-J. Chem. Sci. 2014, 5, 2146.
    3. Yan G.; Wu X.; Yang M. Org. Biomol. Chem. 2013, 11, 5558. - PubMed

    1. For examples of Rh(III)-catalyzed C–H bond additions to destabilized, highly electron-deficient aldehydes to provide alcohols, see:

    2. Li Y.; Zhang X.-S.; Chen K.; He K.-H.; Pan F.; Li B.-J.; Shi Z.-J. Org. Lett. 2012, 14, 636. - PubMed
    3. Li Y.; Zhang X.-S.; Zhu Q.-L.; Shi Z.-J. Org. Lett. 2012, 14, 4498. - PubMed
    4. Yang L.; Correia C. A.; Li C.-J. Adv. Synth. Catal. 2011, 353, 1269.

    1. For examples of Ir-, Re-, and Mn-catalyzed C–H bond addition to aldehydes with capture of alcohol products as silyl ethers, see:

    2. Li B.-J.; Shi Z.-J. Chem. Sci. 2011, 2, 488.
    3. Kuninobu Y.; Asanoma D.; Takai K. Synlett 2010, 2883.
    4. Kuninobu Y.; Fujii Y.; Matsuki T.; Nishina Y.; Takai K. Org. Lett. 2009, 11, 2711. - PubMed
    5. Kuninobu Y.; Nishina Y.; Takeuchi T.; Takai K. Angew. Chem., Int. Ed. 2007, 46, 6518. - PubMed
    6. Fukumoto Y.; Sawada K.; Hagihara M.; Chatani N.; Murai S. Angew. Chem., Int. Ed. 2002, 41, 2779. - PubMed

Publication types