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
. 2021 Apr 13;12(18):6429-6436.
doi: 10.1039/d1sc01389k.

Photocatalytic decarboxylative amidosulfonation enables direct transformation of carboxylic acids to sulfonamides

Vu T Nguyen  1 , Graham C Haug  1 , Viet D Nguyen  1 , Ngan T H Vuong  1 , Hadi D Arman  1 , Oleg V Larionov  1
Affiliations

Photocatalytic decarboxylative amidosulfonation enables direct transformation of carboxylic acids to sulfonamides

Vu T Nguyen et al. Chem Sci. .

Abstract

Sulfonamides feature prominently in organic synthesis, materials science and medicinal chemistry, where they play important roles as bioisosteric replacements of carboxylic acids and other carbonyls. Yet, a general synthetic platform for the direct conversion of carboxylic acids to a range of functionalized sulfonamides has remained elusive. Herein, we present a visible light-induced, dual catalytic platform that for the first time allows for a one-step access to sulfonamides and sulfonyl azides directly from carboxylic acids. The broad scope of the direct decarboxylative amidosulfonation (DDAS) platform is enabled by the efficient direct conversion of carboxylic acids to sulfinic acids that is catalyzed by acridine photocatalysts and interfaced with copper-catalyzed sulfur-nitrogen bond-forming cross-couplings with both electrophilic and nucleophilic reagents.

PubMed Disclaimer

Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. Decarboxylative amidosulfonation as an enabling synthetic tool for the direct conversion of carboxylic acids to sulfonamides.
Fig. 2
Fig. 2. Tricomponent synthesis of sulfonamides and sulfonyl azides by the dual catalytic direct decarboxylative amidosulfonation.
Scheme 1
Scheme 1. Scope of the direct decarboxylative amidosulfonation with O-benzylhydoxylamines. Reaction conditions: carboxylic acid (0.15–0.3 mmol), DABSO (0.33 mmol), A1 (10 mol%), CuF2 (10 mol%) O-benzoylhydroxylamine (0.6 mmol), CH2Cl2 (6 mL), LED light (400 nm).
Scheme 2
Scheme 2. Scope of the direct decarboxylative amidosulfonation of anilines. Reaction conditions: aniline (0.3 mmol), carboxylic acid (0.6–0.75 mmol), CuOTf·½PhMe (10 mol%), A2 (7 mol%), DABSO (0.45 mmol), tBuO2Bz (0.36–0.45 mmol), CH2Cl2 (3 mL), LED light (400 nm). aA1 (7 mol%). bA3 (10 mol%), Cu(acac)2 (10 mol%).
Scheme 3
Scheme 3. Scope of the direct decarboxylative azidosulfonation. Reaction conditions: carboxylic acid (0.3 mmol), copper 2-thiophenecarboxylate (CuTC) (10 mol%), A1 (10 mol%), DABSO (0.45 mmol), tBuO2Bz (0.75 mmol), NaN3 (0.9 mmol), PhCF3/MeCN (3 : 1, 3 mL), LED light (400 nm), 12 h.
Fig. 3
Fig. 3. Direct decarboxylative amidosulfonation and azidosulfonation of natural products and active pharmaceutical ingredients.
Fig. 4
Fig. 4. Computed energy profiles of the acridine catalyst turnover in the sulfinic acid formation and the Cu-catalyzed N-alkyl and N-aryl amidosulfonation and azidosulfonation, ΔG, kcal mol−1.
See this image and copyright information in PMC

References

    1. The Chemistry of Sulphinic Acids, Esters and their Derivatives, ed. S. Patai, John Wiley & Sons, Ltd, New Jersey, 1990
    2. The Chemistry of Sulphonic Acids, Esters and their Derivatives, ed. S. Patai and Z. Rapport, John Wiley & Sons, New York, 1991
    3. Zhao X. Dimitrijević E. Dong V. M. J. Am. Chem. Soc. 2009;131:3466–3467. - PubMed
    4. Dornan P. K. Kou K. G. M. Houk K. N. Dong V. M. J. Am. Chem. Soc. 2014;136:291. - PMC - PubMed
    5. García-Domínguez A. Müller S. Nevado C. Angew. Chem., Int. Ed. 2017;56:9949–9952. - PubMed
    6. Burke E. G. Gold B. Hoang T. T. Raines R. T. Schomaker J. M. J. Am. Chem. Soc. 2017;139:8029–8037. - PMC - PubMed
    7. Nguyen V. T. Dang H. T. Pham H. H. Nguyen V. D. Flores-Hansen C. Arman H. D. Larionov O. V. J. Am. Chem. Soc. 2018;140:8434–8438. - PMC - PubMed
    8. Ratushnyy M. Kamenova M. Gevorgyan V. Chem. Sci. 2018;9:7193–7197. - PMC - PubMed
    9. Hell S. M. Meyer C. F. Misale A. Sap J. B. I. Christensen K. K. Willis M. C. Trabanco A. A. Gouverneur V. Angew. Chem., Int. Ed. 2020;59:11620–11626. - PMC - PubMed
    10. Nambo M. Tahara Y. Yim J. C.-H. Yokogawa D. Crudden C. M. Chem. Sci. 2021 doi: 10.1039/D1SC00133G. - DOI - PMC - PubMed
    1. Patani G. A. LaVoie E. J. Chem. Rev. 1996;96:3147–3176. - PubMed
    2. Metabolism, Pharmacokinetics and Toxicity of Functional Groups, ed. D. A. Smith, Royal Society of Chemistry: London, United Kingdom, 2010, pp. 99–167, 210–274
    3. Ilardi E. A. Vitaku E. Njardarson J. T. J. Med. Chem. 2014;57:2832–2842. - PubMed
    4. Scott K. A. Njardarson J. T. Top. Curr. Chem. 2018;376:5. - PubMed
    1. Friedman H. L., Influence of isosteric replacements upon biological activity, NAS-NRS, Washington, DC, 1951, vol. 206, pp. 295–358, NAS-NRS Publication No. 206

    1. For examples of non-decarboxylative one-step intermolecular tricomponent approaches to aromatic sulfonamides, see:

    2. Nguyen B. Emmett E. J. Willis M. C. J. Am. Chem. Soc. 2010;132:16372–16373. - PubMed
    3. Tsai A. S. Curto J. M. Rocke B. N. Dechert-Schmitt A. M. R. Ingle G. K. Mascitti V. Org. Lett. 2016;18:508–511. - PubMed
    4. Liu N. -W. Liang S. Manolikakes G. Adv. Synth. Catal. 2017;359:1308–1319.
    5. Chen Y. Murray P. R. Davies A. T. Willis M. C. J. Am. Chem. Soc. 2018;140:8781–8787. - PubMed
    6. Zhang F. Zheng D. Lai L. Cheng J. Sun J. Wu J. Org. Lett. 2018;20:1167–1170. - PubMed
    7. Marset X. Torregrosa-Crespo J. Martínez-Espinosa R. M. Guillena G. Ramón D. J. Green Chem. 2019;21:4127–4132.
    8. Wang X. Yang M. Kuang Y. Liu J.-B. Fan X. Wu J. Chem. Commun. 2020;56:3437–3440. - PubMed
    9. Blum S. P. Karakaya T. Schollmeyer D. Klapars A. Waldvogel S. R. Angew. Chem., Int. Ed. 2021;60:5056–5062. - PMC - PubMed

    10. For examples of stepwise and one-pot approaches, see:

    11. Shavnya A. Coffey S. B. Hesp K. D. Ross S. C. Tsai A. S. Org. Lett. 2016;18:5848–5851. - PubMed
    12. Jiang Y.-Y. Wang Q.-Q. Liang S. Hu L.-M. Little R. D. Zeng C.-C. J. Org. Chem. 2016;81:4713–4719. - PubMed
    13. Kim D.-K. Um H.-S. Park H. Kim S. Choi J. Lee C. Chem. Sci. 2020;11:13071–13078. - PMC - PubMed

    14. For examples of other C–S bond forming approaches to sulfonamides, see:

    15. Hell S. M. Meyer C. F. Laudadio G. Misale A. Willis M. C. Noël T. Trabanco A. A. Gouverneur V. J. Am. Chem. Soc. 2020;142:720–725. - PubMed
    16. Davies T. Q. Tilby M. J. Skolc D. Hall A. Willis M. C. Org. Lett. 2020;22:9495–9499. - PMC - PubMed

    17. For examples of intermolecular tricomponent syntheses of aliphatic N-aminosulfonamides, see:

    18. Li Y. Zheng D. Li Z. Wu J. Org. Chem. Front. 2016;3:574–578.
    19. Zhou K. Xia H. Wu J. Org. Chem. Front. 2016;3:865–869.

    20. For other recent approaches to sulfonamides that do not involve C–S bond formation, see:

    21. Hayashi E. Yamaguchi Y. Kita Y. Kamata K. Hara M. Chem. Commun. 2020;56:2095–2098. - PubMed
    22. Laudadio G. Barmpoutsis E. Schotten C. Struik L. Govaerts S. Browne D. L. Noël T. J. Am. Chem. Soc. 2019;141:5664–5668. - PMC - PubMed
    23. Tota A. St John-Campbell S. Briggs E. L. Estevez G. O. Afonso M. Degennaro L. Luisi R. Bull J. A. Org. Lett. 2018;20:2599–2602. - PubMed
    1. Bioactive Carboxylic Compound Classes: Pharmaceuticals and Agrochemicals, ed. C. Lamberth and J. Dinges, Wiley, 2016
    2. Iglesias J. Martínez-Salazar I. Maireles-Torres P. Martin Alonso D. Mariscal R. López Granados M. Chem. Soc. Rev. 2020;49:5704–5771. - PubMed
    3. Sinha J. Podgórski M. Huang S. Bowman C. N. Chem. Commun. 2018;54:3034–3037. - PMC - PubMed