Transition Metal/Photoredox-catalyzed Cascade Reactions Involving Annulation for Accessing Functionalized Heterocycles

Abstract

Cascade reactions are highly effective, atom- and step-economical processes in organic synthesis, which are widely used for the streamlined construction of various molecular architectures. Although there are several types of cascade reactions reported in the literature, one involving annulation as the key step is more captivating as it gives quick access to various heterocyclic compounds in a short and effective manner. In this account, our group’s efforts toward cascade addition/functionalization followed by annulation of simple substrates for accessing various bio-relevant heterocycles and drug derivatives will be presented. We have used photocatalysis for cascade addition-annulation type reactions, transition metal catalysis for cascade C–H acyl methylation-annulation, and finally dual transition metal-photoredox catalysis for the cascade C–H olefination-annulation of carboxylic acids. Using these strategies, a broad range of structurally complex heterocyclic scaffolds, including dihydroquinazolinones, chromanes, benzoxazines, julolidine, etc., were synthesized.

Keywords

Cascade reaction - Annulation - Radical chemistry - Transition metal catalysis - Photoredox catalysis

Publication History

Received: 28 September 2025

Accepted after revision: 27 October 2025

Accepted Manuscript online:
27 October 2025

Article published online:
20 November 2025

• References

• 1 Robinson R. J Chem Soc, Trans 1917; 111: 762
• 2 Sun S, Zhou C, Cheng J. Tetrahedron Lett 2019; 60: 150926
• 3 Liu T, Zheng D, Li Z, Wu J. Adv Synth Catal 2018; 360: 865
• 4 Babu SS, Gopinath P. J Org Chem 2022; 87: 9414
• 5 Yadav P, Sinha P, Gopinath P. J Org Chem 2025; 90 (03) 1333-1343
• 6 Yadav P, Varma AA, Gopinath P. Chem Commun. 2025
• 7 Shaji AP, Sudarshan N, König B, Gopinath P. J Org Chem. 2025
• 8 Parrino B, Carbone A, Muscarella M. et al. J Med Chem 2014; 57: 9495
• 9 Hu E, Kunz RK, Rumfelt S. et al. Bioorg Med Chem Lett 2012; 22: 2262
• 10 Smith CR, Dougan DR, Komandla M. et al. J Med Chem 2015; 58: 5437
• 11 Hu E, Kunz RK, Rumfelt S. et al. Treanor, Bioorg Med Chem Lett 2012; 22: 2262
• 12 Garofalo AW, Adler M, Aubele DL. et al. Bioorg Med Chem Lett 2013; 23: 71
• 13 Song C, Yang C, Zhang F, Wang J, Zhu J. Org Lett 2016; 18
• 14 Prabhakar Ganesh PSK, Muthuraja P, Gopinath P. Chem Commun 2022; 58: 4211
• 15 Huang J, Shi Q, Choudhry N. et al. ACS Med Chem Lett 2022; 13: 1091
• 16 Zhi X, Zhang Y, Huang J, Xu H. Sci Rep. 2017 7.
• 17 Huang Y, Li P, Dong XQ, Zhang X. Org Biomol Chem 2018; 16: 8819
• 18 Prabhakar Ganesh PSK, Muthuraja P, Gopinath P. Org Lett 2023; 25: 8361
• 19 Tamanna, Sharma D, Chauhan P. Org Biomol Chem 2023; 21: 2570
• 20 Li J, Wang XL, Li G, Xu PS, Xu KP, Tan GS. J Asian Nat Prod Res 2017; 19: 1108
• 21 Xie ZP, Zhang HY, Li FC. et al. Chin Chem Lett 2012; 23: 941
• 22 Liu K, Ji Y, Xie Y. et al. J Med Chem 2025; 68: 5804
• 23 Rizo-Liendo A, Arberas-Jiménez I, Sifaoui I, Lorenzo-Morales J. et al. Int J Parasitol Drugs Drug Resist 2021; 17: 139
• 24 Luo X, Lin X, Salendra L. et al. Mar Drugs 2017; 15: 204
• 25 Miura M, Tsuda T, Satoh T, Pivsa-Art S, Nomura M. J Org Chem 1998; 63: 5211
• 26 Ackermann L. Pospech, Org Lett 2011; 13: 4153
• 27 Bechtoldt A, Tirler C, Raghuvanshi K, Warratz S, Kornhaaß C, Ackermann L. Angew Chem Int Ed 2016; 55: 264
• 28 Jiang Q, Zhu C, Zhao H, Su W. Chem Asian J 2016; 11: 356
• 29 Wang Y, Xu X, Wu G, Pang B, Liao S, Ji Y. Org Lett 2022; 24: 821
• 30 Dana S, Dey P, Patil SA, Baidya M. Chem Asian J 2020; 15: 564