Desaturation of Amides via Bismuth Photocatalysis

Abstract

Bismuth redox catalysis has been intensively developed in recent years, enabling diverse transformations that were previously thought to be achievable only through transition metal catalysis. In this study, we present the desaturation of amides to generate the enamides, an important structural motif in pharmaceuticals, via bismuth photocatalysis. The protocol involves a combination of unique mechanistic steps recently uncovered for bismuth thus allowing for the translation of a canonical transition metal–mediated transformation into a main group–based catalytic system.

Keywords

Bismuth - Low-valent bismuth - Bismuth redox catalysis - Bismuth photocatalysis - Desaturation - Amides

Publication History

Received: 23 June 2025

Accepted after revision: 18 August 2025

Accepted Manuscript online:
18 August 2025

Article published online:
02 October 2025

• References

• 1a Flatt B, Martin R, Wang TL. et al. J Med Chem 2009; 52: 904
• 1b Perez-Sayans M, Somoza-Martin JM, Barros-Angueira F, Rey JMG, Garcia-Garcia A. Cancer Treat Rev 2009; 35: 707
• 1c Fu J, Si P, Zheng M. et al. Bioorg Med Chem Lett 2012; 22: 6848
• 1d Poulsen TB. Acc Chem Res 1830; 2021: 54
• 2a Courant T, Dagousset G, Masson G. Synthesis 2015; 47: 1799
• 2b Beltran F, Miesch L. Synthesis 2020; 52: 2497
• 2c Bouchet D, Varlet T, Masson G. Acc Chem Res 2022; 55: 3265

For selected examples for desaturation via C–H activation strategies, see:
• 3a Bolig AD, Brookhart M. J Am Chem Soc 2007; 129: 14544
• 3b Voica A-F, Mendoza A, Gutekunst WR, Fraga JO, Baran PS. Nat Chem 2012; 4: 629
• 3c Bheeter CB, Jin R, Bera JK, Dixneuf PH, Doucet H. Adv Synth Catal 2014; 356: 119
• 3d Chuentragool P, Parasram M, Shi Y, Gevorgyan V. J Am Chem Soc 2018; 140: 2465
• 3e Li G, Kates PA, Dilger AK, Cheng PT, Ewing WR, Groves JT. ACS Catal 2019; 9: 9513
• 3f Huang L, Bismuto A, Rath SA, Trapp N, Morandi B. Angew Chem, Int Ed 2021; 60: 7290
• 3g Spieß P, Berger M, Kaiser D, Maulide N. J Am Chem Soc 2021; 143: 10524
• 3h Xia Y, Jana K, Studer A. Chem – Eur J 2021; 27: 16621
• 3i Stateman LM, Dare RM, Paneque AN, Nagib DA. Chem 2022; 8: 210
• 3j Yang S, Fan H, Xie L, Dong G, Chen M. Org Lett 2022; 24: 6460
• 3k Wang C, Azofra LM, Dam P. et al. ACS Catal 2022; 12: 8868
• 3l Li X, Cheng Z, Liu J, Zhang Z, Song S, Jiao N. Chem Sci 2022; 13: 9056-9061
• 3m Ritu, Kolb D, Jain N, König B. Adv Synth Catal 2023; 365: 605
• 3n An S, Lai G, Liu WH. Chem Sci 2024; 15: 15385
• 3o Zhao C, Gao R, Ma W. et al. Nat Commun 2024; 15: 4329
• 3p Novaes LFT, Ho JSK, Mao K, Villemure E, Terrett JA, Lin S. J Am Chem Soc 2024; 146: 22982

For recent reviews, see:
• 4a Lipshultz JM, Li G, Radosevich AT. J Am Chem Soc 2021; 143: 1699
• 4b Moon HW, Cornella J. ACS Catal 2022; 12: 1382
• 4c Mato M, Cornella J. Angew Chem, Int Ed 2024; 63: e202315046
• 5a Wang F, Planas O, Cornella J. J Am Chem Soc 2019; 141: 4235
• 5b Pang Y, Leutzsch M, Nöthling N, Cornella J. J Am Chem Soc 2020; 142: 19473
• 5c Pang Y, Leutzsch M, Nöthling N, Katzenburg F, Cornella J. J Am Chem Soc 2021; 143: 12487
• 5d Mato M, Spinnato D, Leutzsch M, Moon HW, Reijerse EJ, Cornella J. Nat Chem 2023; 15: 1138
• 5e Mato M, Bruzzese PC, Takahashi F. et al. J Am Chem Soc 2023; 145: 18742
• 5f Moon HW, Wang F, Bhattacharyya K. et al. Angew Chem, Int Ed 2023; 62: e202313578
• 5g Tsuruta T, Spinnato D, Moon HW, Leutzsch, Cornella J. J Am Chem Soc 2023; 145: 25538
• 5h Ni S, Spinnato D, Cornella J. J Am Chem Soc 2024; 146: 22140
• 5i Beland V, Nöthling N, Leutzsch M, Cornella J. J Am Chem Soc 2024; 146: 25409
• 5j Mato M, Stamoulis A, Cleto-Bruzzese P, Cornella J. Angew Chem, Int Ed 2024; 64: e202418367
• 5k Moon HW, Nöthling N, Leutzsch M, Kuziola J, Cornella J. Angew Chem, Int Ed 2024; 64: e202417864
• 5l Stamoulis A, Mato M, Cleto Bruzzese P. et al. J Am Chem Soc 2025; 147: 6037
• 6a Planas O, Wang F, Leutszch M, Cornella J. Science 2020; 367: 313
• 6b Planas O, Peciukenas V, Cornella J. J Am Chem Soc 2020; 142: 11382
• 6c Planas O, Peciukenas V, Leutzsch M, Nöthling N, Pantazis D, Cornella J. J Am Chem Soc 2022; 144: 14489
• 6d Faber T, Engelhardt S, Cornella J. Angew Chem, Int Ed 2025; e202424698
• 7a Magre M, Cornella J. J Am Chem Soc 2021; 143: 21497
• 7b Yang X, Kuziola J, Beland V, Leutzsch M, Bures J, Cornella J. Angew Chem, Int Ed 2023; 62: e202306447
• 8 Šimon P, De Proft F, Jambor R, Růžička A, Dostál L. Angew Chem, Int Ed 2010; 49: 5468
• 9 Hejda M, Jirásko R, Růžička A, Jambor R, Dostál L. Organometallics 2020; 39: 4320
• 10 Guo W, Wang Q, Zhu J. Chem Soc Rev 2021; 50: 7359
• 11 Yi L, Kong D, Kale AP. et al. Angew Chem, Int Ed 2024; 63: e202411961
• 12a Constantin T, Zanini M, Regni A, Sheikh NS, Julia F, Leonori D. Science 2020; 367: 1021
• 12b Juliá F, Constantin T, Leonori D. Chem Rev 2022; 122: 2292