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 Feb 19;15(5):3873-3881.
doi: 10.1021/acscatal.4c07845. eCollection 2025 Mar 7.

Visible-Light-Driven Catalytic Dehalogenation of Trichloroacetic Acid and α-Halocarbonyl Compounds: Multiple Roles of Copper

Abigail J Thillman  1 , Erin C Kill  1 , Alexander N Erickson  1 , Dian Wang  1
Affiliations

Visible-Light-Driven Catalytic Dehalogenation of Trichloroacetic Acid and α-Halocarbonyl Compounds: Multiple Roles of Copper

Abigail J Thillman et al. ACS Catal. .

Abstract

Herein, we report the reaction development and mechanistic studies of visible-light-driven Cu-catalyzed dechlorination of trichloroacetic acid for the highly selective formation of monochloroacetic acid. Visible-light-driven transition metal catalysis via an inner-sphere pathway features the dual roles of transition metal species in photoexcitation and substrate activation steps, and a detailed mechanistic understanding of their roles is crucial for the further development of light-driven catalysis. This catalytic method, which features environmentally desired ascorbic acid as the hydrogen atom source and water/ethanol as the solvent, can be further applied to the dehalogenation of a variety of halocarboxylic acids and amides. Spectroscopic, X-ray crystallographic, and kinetic studies have revealed the detailed mechanism of the roles of copper in photoexcitation, thermal activation of the first C-Cl bond, and excited-state activation of the second C-Cl bond via excited-state chlorine atom transfer.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. General Reaction Schemes for Visible-Light Transition Metal Catalysis via an Inner-Sphere Mechanism and Previous Examples on Light-Driven Cu Catalysis with Carboxylic Acids
Figure 1
Figure 1
Structure of Cu-oxalate isolated from light-driven dechlorination.
Scheme 2
Scheme 2. Characterization of [(tBu2bpy)2CuI] and [(tBu2bpy)2CuIICl] Species
Conditions: (A) Formation of 4a: Cu(OAc)2, tBu2bpy (2.5 equiv), TCA (4 equiv), then ascH2 (16 equiv), Na2CO3 (4 equiv), N2, 2 d; 5a: Cu(OAc)2, tBu2bpy (2.5 equiv), TCA (4 equiv), then ascH2 (16 equiv), Na2CO3 (4 equiv), 440 nm LED, N2, 30 min, then light off, 2 d; the CuCl2– counterion in 4a and 5a is not shown. (B) TCA (0.03 M), Cu(OAc)2 (2 mol %), tBu2bpy (14 mol %), Na2CO3 (1 equiv), ascH2 (4 equiv), EtOH/H2O (3:1) (4 mL), N2, 440 nm LED.
Scheme 3
Scheme 3. Cu-Mediated First C–Cl Cleavage in TCA
Figure 2
Figure 2
Mechanistic studies: (A) Dependence of the reaction rate on bipyridine ligands. Conditions: DCA (0.23 M), Cu(OAc)2·H2O (3 mol %), 4,4′-disubsitituted-2,2′-bipyridine (15 mol %, R = OMe, tBu, H, or Br), ascorbic acid (4 equiv), Na2CO3 (1.2 equiv), EtOH/H2O (3:1 v/v, 1 mL), DMF (5.0 μL, internal standard), 440 nm LED, N2. (B) Deuterium incorporation studies. Conditions: TCA (0.12 M), Cu(OAc)2 (3 mol %), 4,4′-dimethoxy-2,2′-bipyridine (15 mol %), ascorbic acid-d4 (4 equiv), Na2CO3 (1.2 equiv), CD3OD/D2O (3:1 v/v, 1 mL), C6D6 (5.0 μL, internal standard), 440 nm LED, N2.
Figure 3
Figure 3
Proposed mechanism for the catalytic dechlorination of TCA to MCA. AscH2: ascorbic acid; AscH–: ascorbate; Asc•–: ascorbate radical anion; Ascox: dehydroascorbic acid; HAT: hydrogen atom transfer; SET: single electron transfer; T.L.S.: turnover-limiting step.
See this image and copyright information in PMC

References

    1. Visible Light Photocatalysis in Organic Chemistry; Stephenson C. R. J.; Yoon T. P.; MacMillan D. W. C., Eds.; Wiley: Hoboken, NJ, 2018.
    2. Strieth-Kalthoff F.; James M. J.; Teders M.; Pitzer L.; Glorius F. Energy transfer catalysis mediated by visible light: principles, applications, directions. Chem. Soc. Rev. 2018, 47, 7190–7202. 10.1039/C8CS00054A. - DOI - PubMed
    3. Glaser F.; Kerzig C.; Wenger O. S. Multi-Photon Excitation in Photoredox Catalysis: Concepts, Applications Methods.. Angew. Chem. Int. Ed. 2020, 59, 10266–10284. 10.1002/anie.201915762. - DOI - PubMed
    4. Yu X. Y.; Chen J. R.; Xiao W. J. Visible Light-Driven Radical-Mediated C-C Bond Cleavage/Functionalization in Organic Synthesis. Chem. Rev. 2021, 121, 506–561. 10.1021/acs.chemrev.0c00030. - DOI - PubMed
    5. Chan A. Y.; Perry I. B.; Bissonnette N. B.; Buksh B. F.; Edwards G. A.; Frye L. I.; Garry O. L.; Lavagnino M. N.; Li B. X.; Liang Y.; Mao E.; Millet A.; Oakley J. V.; Reed N. L.; Sakai H. A.; Seath C. P.; MacMillan D. W. C. Metallaphotoredox: The Merger of Photoredox and Transition Metal Catalysis. Chem. Rev. 2022, 122, 1485–1542. 10.1021/acs.chemrev.1c00383. - DOI - PubMed
    6. Holmberg-Douglas N.; Nicewicz D. A. Photoredox-Catalyzed C-H Functionalization Reactions. Chem. Rev. 2022, 122, 1925–2016. 10.1021/acs.chemrev.1c00311. - DOI - PMC - PubMed
    7. Pitre S. P.; Overman L. E. Strategic Use of Visible-Light Photoredox Catalysis in Natural Product Synthesis. Chem. Rev. 2022, 122, 1717–1751. 10.1021/acs.chemrev.1c00247. - DOI - PubMed
    8. Li J.; Zhang D.; Hu Z. Ligand-Enabled “Two-in-One” Metallaphotocatalytic Cross Couplings. ACS Catal. 2025, 15, 1635–1654. 10.1021/acscatal.4c07128. - DOI

    1. For a leading review, see:

    2. Cheung K. P. S.; Sarkar S.; Gevorgyan V. Visible Light-Induced Transition Metal Catalysis. Chem. Rev. 2022, 122, 1543–1625. 10.1021/acs.chemrev.1c00403. - DOI - PMC - PubMed
    1. Ting S. I.; Garakyaraghi S.; Taliaferro C. M.; Shields B. J.; Scholes G. D.; Castellano F. N.; Doyle A. G. 3d-d Excited States of Ni(II) Complexes Relevant to Photoredox Catalysis: Spectroscopic Identification and Mechanistic Implications. J. Am. Chem. Soc. 2020, 142, 5800–5810. 10.1021/jacs.0c00781. - DOI - PubMed
    2. Cagan D. A.; Stroscio G. D.; Cusumano A. Q.; Hadt R. G. Multireference Description of Nickel-Aryl Homolytic Bond Dissociation Processes in Photoredox Catalysis. J. Phys. Chem. A 2020, 124, 9915–9922. 10.1021/acs.jpca.0c08646. - DOI - PubMed
    1. Treacy S. M.; Rovis T. Copper Catalyzed C(sp3)- H Bond Alkylation via Photoinduced Ligand-to-Metal Charge Transfer. J. Am. Chem. Soc. 2021, 143, 2729–2735. 10.1021/jacs.1c00687. - DOI - PMC - PubMed
    2. Xu P.; Lopez-Rojas P.; Ritter T. Radical Decarboxylative Carbometalation of Benzoic Acids: A Solution to Aromatic Decarboxylative Fluorination. J. Am. Chem. Soc. 2021, 143, 5349–5354. 10.1021/jacs.1c02490. - DOI - PubMed
    3. Li Q. Y.; Gockel S. N.; Lutovsky G. A.; DeGlopper K. S.; Baldwin N. J.; Bundesmann M. W.; Tucker J. W.; Bagley S. W.; Yoon T. P. Decarboxylative cross-nucleophile coupling via ligand-to-metal charge transfer photoexcitation of Cu(II) carboxylates. Nat. Chem. 2022, 14, 94–99. 10.1038/s41557-021-00834-8. - DOI - PMC - PubMed
    4. Dow N. W.; Pedersen P. S.; Chen T. Q.; Blakemore D. C.; Dechert-Schmitt A. M.; Knauber T.; MacMillan D. W. C. Decarboxylative Borylation and Cross-Coupling of (Hetero)aryl Acids Enabled by Copper Charge Transfer Catalysis. J. Am. Chem. Soc. 2022, 144, 6163–6172. 10.1021/jacs.2c01630. - DOI - PMC - PubMed
    1. Fosshat S.; Siddhiaratchi S. D. M.; Baumberger C. L.; Ortiz V. R.; Fronczek F. R.; Chambers M. B. Light-Initiated C-H Activation via Net Hydrogen Atom Transfer to a Molybdenum(VI) Dioxo. J. Am. Chem. Soc. 2022, 144, 20472–20483. 10.1021/jacs.2c09235. - DOI - PubMed

LinkOut - more resources