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
. 2024 Mar;11(9):e2306923.
doi: 10.1002/advs.202306923. Epub 2023 Dec 13.

Ligand Relay for Nickel-Catalyzed Decarbonylative Alkylation of Aroyl Chlorides

Tian-Zhang Wang  1 , Yu-Qiu Guan  1 , Tian-Yu Zhang  1 , Yu-Feng Liang  1
Affiliations

Ligand Relay for Nickel-Catalyzed Decarbonylative Alkylation of Aroyl Chlorides

Tian-Zhang Wang et al. Adv Sci (Weinh). 2024 Mar.

Abstract

Transition metal-catalyzed direct decarboxylative transformations of aromatic carboxylic acids usually require high temperatures, which limit the substrate's scope, especially for late-stage applications. The development of the selective decarbonylative of carboxylic acid derivatives, especially the most fundamental aroyl chlorides, with stable and cheap electrophiles under mild conditions is highly desirable and meaningful, but remains challenging. Herein, a strategy of nickel-catalyzed decarbonylative alkylation of aroyl chlorides via phosphine/nitrogen ligand relay is reported. The simple phosphine ligand is found essential for the decarbonylation step, while the nitrogen ligand promotes the cross-electrophile coupling. Such a ligand relay system can effectively and orderly carry out the catalytic process at room temperature, utilizing easily available aroyl chlorides as an aryl electrophile for reductive alkylation. This discovery provides a new strategy for direct decarbonylative coupling, features operationally simple, mild conditions, and excellent functional group tolerance. The mild approach is applied to the late-stage methylation of various pharmaceuticals. Extensive experiments are carried out to provide insights into the reaction pathway and support the ligand relay process.

Keywords: alkylation; aroyl chlorides; cross electrophiles coupling; decarbonylation; ligand relay; nickels.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Ni‐catalyzed cross coupling of carboxylic acid derivatives.
Scheme 2
Scheme 2
Scope of decarbonylative alkylation of acid chlorides with alkyl electrophiles.
Scheme 3
Scheme 3
Decarbonylative methylation of complex molecules.
Figure 1
Figure 1
Stoichiometric reactions of Ni(cod)2, triphenylphosphine with o‐toluoyl chloride. The 31P NMR spectra of (A) [Ni0](dpph) 7, (B) reaction at −20 °C for 5 min, (C) reaction at room temperature for 5 min, (D) aryl nickel specie 9
Scheme 4
Scheme 4
Studies of the influences of ligands.
Scheme 5
Scheme 5
Mechanistic experiments.
Scheme 6
Scheme 6
Proposed ligand relay mechanism.
See this image and copyright information in PMC

References

    1. a) Xue W., Jia X., Wang X., Tao X., Yin Z., Gong H., Chem. Soc. Rev. 2021, 50, 4162; - PubMed
    2. b) Huang S., Wang M., Jiang X., Chem. Soc. Rev. 2022, 51, 8351; - PubMed
    3. c) Sun X.‐Y., Yao B.‐Y., Xuan B., Xiao L.‐J., Zhou Q.‐L., Chem Catal. 2022, 2, 3140;
    4. d) Li Z., Li C., Ding Y., Huo H., Coord. Chem. Rev. 2022, 460, 214479.
    1. a) Khusnutdinova J. R., Milstein D., Angew. Chem., Int. Ed. 2015, 54, 12236; - PubMed
    2. b) Hansen E. C., Pedro D. J., Wotal A. C., Gower N. J., Nelson J. D., Caron S., Weix D. J., Nat. Chem. 2016, 8, 1126; - PMC - PubMed
    3. c) Wu K., Doyle A. G., Nat. Chem. 2017, 9, 779; - PMC - PubMed
    4. d) Kapat A., Sperger T., Guven S., Schoenebeck F., Science 2019, 363, 391; - PubMed
    5. e) Clevenger A. L., Stolley R. M., Aderibigbe J., Louie J., Chem. Rev. 2020, 120, 6124; - PubMed
    6. f) Prieto Kullmer C. N., Kautzky J. A., Krska S. W., Nowak T., Dreher S. D., MacMillan D. W. C., Science 2022, 376, 532; - PMC - PubMed
    7. g) Qi L., Pan Q.‐Q., Wei X.‐X., Pang X., Liu Z., Shu X.‐Z., J. Am. Chem. Soc. 2023, 145, 13008. - PubMed
    1. a) Alig L., Fritz M., Schneider S., Chem. Rev. 2019, 119, 2681; - PubMed
    2. b) Wang H., Wen J., Zhang X., Chem. Rev. 2021, 121, 7530; - PubMed
    3. c) Huang Y., Hayashi T., Chem. Rev. 2022, 122, 14346. - PubMed
    1. a) Reetz M. T., Angew. Chem., Int. Ed. 2008, 47, 2556; - PubMed
    2. b) Ambrosini L. M., Lambert T. H., ChemCatChem 2010, 2, 1373;
    3. c) Martínez S., Veth L., Lainer B., Dydio P., ACS Catal. 2021, 11, 3891.
    1. a) Fors B. P., Buchwald S. L., J. Am. Chem. Soc. 2010, 132, 15914; - PMC - PubMed
    2. b) Li H., Ma B., Liu Q.‐S., Wang M.‐L., Wang Z.‐Y., Xu H., Li L.‐J., Wang X., Dai H.‐X., Angew. Chem., Int. Ed. 2020, 59, 14388; - PubMed
    3. c) Wang G.‐Y., Ge Z., Ding K., Wang X., Angew. Chem., Int. Ed. 2023, 62, e202307973. - PubMed

LinkOut - more resources