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
. 2025 Jan 22;147(3):2476-2490.
doi: 10.1021/jacs.4c13086. Epub 2025 Jan 10.

Mechanistic Investigations of Cobalt-Catalyzed, Aminoquinoline-Directed C(sp2)-H Bond Functionalization

Lukass Lukasevics  1 , George N Oh  1 , Xiqu Wang  1 , Liene Grigorjeva  2 , Olafs Daugulis  1
Affiliations

Mechanistic Investigations of Cobalt-Catalyzed, Aminoquinoline-Directed C(sp2)-H Bond Functionalization

Lukass Lukasevics et al. J Am Chem Soc. .

Abstract

Monoanionic, bidentate-auxiliary-directed, cobalt-catalyzed C-H bond functionalization has become a very useful tool in organic synthesis. A comprehensive investigation into isolated organometallic intermediates and their reactivity within the catalytic cycle is lacking. We report here mechanistic studies of cobalt-catalyzed, aminoquinoline-directed C(sp2)-H bond functionalization. A number of organometallic Co(III) intermediates have been isolated and structurally characterized, including, for the first time in the aminoquinoline system, complexes arising from migratory insertion into cobalt-carbon bonds. The catalytic and stoichiometric reactions of cobalt(III) aryls with alkenes, alkynes, carbon monoxide, cyclic secondary amines, and aminoquinoline benzamides have been explored. The oxidation state of cobalt intermediates in the product-forming step depends on the nature of the coupling component. Specifically, annulation with alkynes and carbonylation with CO likely proceed via a Co(I)/Co(III) catalytic cycle. Carbon-hydrogen bond functionalization with alkenes and amines, as well as benzamide homocoupling, likely proceed via a (formally) Co(IV) species and involve oxidatively induced reductive elimination.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

Similar articles

See all similar articles

References

    1. General reviews on C–H bond functionalization:Durham AC; Wang Y; Wang Y-M Redox-Neutral Propargylic C–H Functionalization by Using Iron Catalysis. Synlett 2020, 31, 1747–1752.
    2. Baudoin O Multiple Catalytic C–H Bond Functionalization for Natural Product Synthesis. Angew. Chem., Int. Ed 2020, 59, 17798–17809. - PubMed
    3. Guillemard L; Kaplaneris N; Ackermann L; Johansson MJ Late-stage C–H functionalization offers new opportunities in drug discovery. Nat. Rev. Chem 2021, 5, 522–545. - PubMed
    4. Abrams DJ; Provencher PA; Sorensen EJ Recent applications of C–H functionalization in complex natural product synthesis. Chem. Soc. Rev 2018, 47, 8925–8967. - PubMed
    5. Mo J; Messinis AM; Li J; Warratz S; Ackermann L Chelation-Assisted Iron-Catalyzed C–H Activations: Scope and Mechanism. Acc. Chem. Res 2024, 57, 10–22. - PMC - PubMed
    6. Zhang Z; Chen P; Liu G Copper-catalyzed radical relay in C(sp3)–H functionalization. Chem. Soc. Rev 2022, 51, 1640–1658. - PubMed
    7. Gandeepan P; Müller T; Zell D; Cera G; Warratz S; Ackermann L 3d Transition Metals for C–H Activation. Chem. Rev 2019, 119, 2192–2452. - PubMed
    8. Lukasevics L; Cizikovs A; Grigorjeva L C–H Bond Functionalization by High-Valent Cobalt Catalysis: Current Progress, Challenges, and Future Perspectives. Chem. Commun 2021, 57, 10827–10841. - PubMed
    9. Shang R; Ilies L; Nakamura E Iron-Catalyzed C–H Bond Activation. Chem. Rev 2017, 117, 9086–9139. - PubMed
    10. Khake SM; Chatani N Nickel-Catalyzed C–H Functionalization Using A Non-directed Strategy. Chem 2020, 6, 1056–1081.
    11. He G; Wang B; Nack WA; Chen G Syntheses and Transformations of α-Amino Acids via Palladium-Catalyzed Auxiliary-Directed sp3 C–H Functionalization. Acc. Chem. Res 2016, 49, 635–645. - PubMed
    12. Hartwig JF Evolution of C–H Bond Functionalization from Methane to Methodology. J. Am. Chem. Soc 2016, 138, 2–24. - PMC - PubMed
    13. Gao K; Yoshikai N Low-Valent Cobalt Catalysis: New Opportunities for C–H Functionalization. Acc. Chem. Rev 2014, 47, 1208–1219. - PubMed
    14. Pototschnig G; Maulide N; Schnürch M Direct Functionalization of C–H Bonds by Iron, Nickel, and Cobalt Catalysis. Chem.Eur. J 2017, 23, 9206–9232. - PubMed
    15. Garai B; Das A; Kumar DV; Sundararaju B Enantioselective C–H bond functionalization under Co(iii)-catalysis. Chem. Commun 2024, 60, 3354–3369. - PubMed
    16. Yoshino T; Matsunaga S (Pentamethylcyclopentadienyl)cobalt(III)-Catalyzed C–H Bond Functionalization: From Discovery to Unique Reactivity and Selectivity. Adv. Synth. Catal 2017, 359, 1245–1262.
    17. St. John-Campbell S; Bull JA Base Metal Catalysis in Directed C(sp3)–H Functionalisation. Adv. Synth. Catal 2019, 361 (16), 3662–3682.
    1. Daugulis O; Roane J; Tran LD Bidentate, Monoanionic Auxiliary-Directed Functionalization of Carbon–Hydrogen Bonds. Acc. Chem. Res 2015, 48, 1053–1064. - PMC - PubMed
    2. Rej S; Ano Y; Chatani N Bidentate Directing Groups: An Efficient Tool in C–H Bond Functionalization Chemistry for the Expedient Construction of C–C Bonds. Chem. Rev 2020, 120, 1788–1887. - PubMed
    3. Talukdar K; Shah TA; Sarkar T; Roy S; Maharana PK; Punniyamurthy T Pd-catalyzed bidentate auxiliary assisted remote C(sp3)–H functionalization. Chem. Commun 2021, 57, 13221–13233. - PubMed
    4. Liu J; Chen G; Tan Z Copper-Catalyzed or -Mediated C-H Bond Functionalizations Assisted by Bidentate Directing Groups. Adv. Synth. Catal 2016, 358, 1174–1194.
    5. Rit RK; Yadav R; Ghosh K; Sahoo AK Reusable directing groups [8-aminoquinoline, picolinamide, sulfoximine] in C(sp3)–H bond activation: present and future. Tetrahedron 2015, 71, 4450–4459.
    1. Zaitsev VG; Shabashov D; Daugulis O Highly Regioselective Arylation of sp3 C-H Bonds Catalyzed by Palladium Acetate. J. Am. Chem. Soc 2005, 127, 13154–13155. - PubMed
    2. Shabashov D; Daugulis O Auxiliary-Assisted Palladium-Catalyzed Arylation and Alkylation of sp2 and sp3 Carbon-Hydrogen Bonds. J. Am. Chem. Soc 2010, 132, 3965–3972. - PMC - PubMed
    1. Selected examples on aminoquinoline-directed, Cu, Fe, Ni, Mn, and Cr-catalyzed C–H bond functionalization:Chatani N Nickel-Catalyzed Functionalization Reactions Involving C–H Bond Activation via an Amidate-Promoted Strategy and Its Extension to the Activation of C–F, C–O, C–S, and C–CN Bonds. Acc. Chem. Res 2023, 56, 3053–3064. - PubMed
    2. Tran LD; Popov I; Daugulis O Copper-Promoted Sulfenylation of sp2 C–H Bonds. J. Am. Chem. Soc 2012, 134, 18237–18240. - PMC - PubMed
    3. Shang R; Ilies L; Matsumoto A; Nakamura E β-Arylation of Carboxamides via Iron-Catalyzed C(sp3)–H Bond Activation. J. Am. Chem. Soc 2013, 135, 6030–6032. - PubMed
    4. Nishino M; Hirano K; Satoh T; Miura M Copper-Mediated C-H/C-H Biaryl Coupling of Benzoic Acid Derivatives and 1,3-Azoles. Angew. Chem. Int. Ed 2013, 52, 4457–4461. - PubMed
    5. Monks BM; Fruchey ER; Cook SP Iron-Catalyzed C(sp2)-H Alkylation of Carboxamides with Primary Electrophiles. Angew. Chem., Int. Ed 2014, 53, 11065–11069. - PubMed
    6. Tang J; Liu P; Zeng X N-Heterocyclic carbene–chromium-catalyzed alkylative cross-coupling of benzamide derivatives with aliphatic bromides. Chem. Commun 2018, 54, 9325–9328. - PubMed
    7. Sato T; Yoshida T; Al Mamari H; Ilies L; Nakamura E Manganese-Catalyzed Directed Methylation of C(sp2)–H Bonds at 25 °C with High Catalytic Turnover. Org. Lett 2017, 19 (19), 5458–5461. - PubMed
    8. Roane J; Daugulis O A General Method for Aminoquinoline-Directed, Copper-Catalyzed sp2 CH Bond Amination. J. Am. Chem. Soc 2016, 138, 4601–4607. - PMC - PubMed
    1. Grigorjeva L; Daugulis O Cobalt-Catalyzed, Aminoquinoline-Directed C(sp2)-H Bond Alkenylation by Alkynes. Angew. Chem., Int. Ed 2014, 53, 10209–10212. - PMC - PubMed
    2. Grigorjeva L; Daugulis O Cobalt-Catalyzed, Aminoquinoline-Directed Coupling of sp2 C–H Bonds with Alkenes. Org. Lett 2014, 16, 4684–4687. - PMC - PubMed
    3. Grigorjeva L; Daugulis O Cobalt-Catalyzed Direct Carbonylation of Aminoquinoline Benzamides. Org. Lett 2014, 16, 4688–4690. - PMC - PubMed
    4. Grigorjeva L; Daugulis O Cobalt-Promoted Dimerization of Aminoquinoline Benzamides. Org. Lett 2015, 17, 1204–1207. - PMC - PubMed
    5. Nguyen TT; Grigorjeva L; Daugulis O Aminoquinoline-directed, cobalt-catalyzed carbonylation of sulfonamide sp2 C–H bonds. Chem. Commun 2017, 53, 5136–5138. - PMC - PubMed
    6. Nguyen TT; Grigorjeva L; Daugulis O Cobalt-Catalyzed, Aminoquinoline-Directed Functionalization of Phosphinic Amide sp2 C–H Bonds. ACS Catal 2016, 6, 551–554. - PMC - PubMed

LinkOut - more resources