Organophosphoric Acid Catalyzed Cyclization–Aromatization of 3-Vinylindoles and 2-Vinylpyridines to Access C3N2 Carbazole–Pyridine Frameworks

Abstract

A practical, organophosphoric acid-catalyzed, two-component cyclization–aromatization reaction of 3-vinylindoles with 2-vinylpyridines has been established for the efficient assembly of various functionalized 1-pyridin-2-yl-9H-carbazole skeletons. This transformation involves an organophosphoric acid-catalyzed [4+2] cycloaddition reaction, together with a tandem oxidative aromatization process. This synthetic methodology, characterized by mild reaction conditions, outstanding functional-group tolerance, and a scalable synthesis capability, has the potential to support in-depth explorations in the fields of materials science and biomedicine.

Key words

phosphoric acid catalysis - vinylindoles - vinylpyridines - [4+2] cycloaddition - oxidative aromatization - pyridinylcarbazoles

Publication History

Received: 07 January 2025

Accepted after revision: 04 March 2025

Accepted Manuscript online:
04 March 2025

Article published online:
29 April 2025

• References and Notes

• 1a Bourget-Merle L, Lappert MF, Severn JR. Chem. Rev. 2002; 102: 3031
• 1b Mudadu MS, Singh AN, Thummel RP. J. Org. Chem. 2008; 73: 6513
• 1c Blacquiere JM. ACS Catal. 2021; 11: 5416
• 2a Do DC. H, Keyser A, Protchenko AV, Maitland B, Pernik I, Niu H, Kolychev EL, Rit A, Vidovic D, Stasch A, Jones C, Aldridge S. Chem. Eur. J. 2017; 23: 5830
• 2b Cheng J, Wang L, Wang P, Deng L. Chem. Rev. 2018; 118: 9930
• 3a Zhao X, Hou Y, Liu L, Zhao J. Energy Fuels 2021; 35: 18942
• 3b Zhang J, Ju L, Tang Z, Zhang S, Zhang G, Wang W. ACS Appl. Nano Mater. 2024; 7: 24653
• 4a Más-Montoya M, Montenegro MF, Ferao AE, Tárraga A, Rodríguez-López JN, Curiel D. Org. Lett. 2020; 22: 3356
• 4b Baumes JM, Gassensmith JJ, Giblin J, Lee J.-J, White AG, Culligan WJ, Leevy WM, Kuno M, Smith BD. Nat. Chem. 2010; 2: 1025
• 5a Jin J.-L, Li H.-B, Geng Y, Wu Y, Duan Y.-A, Su Z.-M. ChemPhysChem 2012; 13: 3714
• 5b Araneda JF, Piers WE, Heyne B, Parvez M, McDonald R. Angew. Chem. Int. Ed. 2011; 50: 12214
• 5c Liu Y, Yang L, Ma C, Tang A. Dyes Pigm. 2020; 173: 107981
• 5d Más-Montoya, Alcaraz AG, Ferao AE, Bautista D, Curiel D. Dyes Pigm. 2023; 209: 110924
• 6 Kim S, Ko S, Kim M, Ye J, Yoo B, Lee H, Hwang J. EP 3461829, 2019
• 7a Kong RY, Parry JB, Anello GR, Ong ME, Lancaster KM. J. Am. Chem. Soc. 2023; 145: 24136
• 7b Zhang G, Cai X, Jia J, Feng B, Yang K, Song Q. ACS Catal. 2023; 13: 9502
• 7c Zhao M, Ren F, Zhou Y. Chem. Eur. J. 2024; 30: e202401784
• 8a Moustakim M, Riedel K, Schuller M, Gehring AP, Monteiro OP, Martin SP, Fedorov O, Heer J, Dixon DJ, Elkins JM, Knapp S, Bracher F, Brennan PE. Bioorg. Med. Chem. 2018; 26: 2965
• 8b Yamamoto K, Matsui S, Kato S.-i, Nakamura Y. Org. Biomol. Chem. 2023; 21: 5398
• 8c Miyaura N, Suzuki A. Chem. Rev. 1995; 95: 2457
• 8d Suzuki A. Angew. Chem. Int. Ed. 2011; 50: 6722
• 9a Negishi E.-i, King AO, Okukado N. J. Org. Chem. 1977; 42: 1821
• 9b Negishi E.-i. Angew. Chem. Int. Ed. 2011; 50: 6738
• 10a Sridharan V, Martín MA, Menéndez JC. Synlett 2006; 2375 
• 10b Liégault B, Lee D, Huestis MP, Stuart DR, Fagnou K. J. Org. Chem. 2008; 73: 5022
• 11a Wolfe JP, Wagaw S, Buchwald SL. J. Am. Chem. Soc. 1996; 118: 7215
• 11b Driver MS, Hartwig JF. J. Am. Chem. Soc. 1996; 118: 7217
• 11c Forero-Cortés PA, Haydl AM. Org. Process Res. Dev. 2019; 23: 1478
• 12 Kumar S, Jyoti J, Gupta D, Singh G, Kumar A. SynOpen 2023; 7: 580
• 13 Hu Z, Men Y, Xu Z, Wu T, Xu X, Tang B. Org. Chem. Front. 2020; 7: 3720
• 14a Meek JS, Merrow RT, Cristol SJ. J. Am. Chem. Soc. 1952; 74: 2667
• 14b Doering W. vonE, Rhoads SJ. J. Am. Chem. Soc. 1953; 75: 4738
• 14c Davis AE, Lowe JM, Hilinski MK. Chem. Sci. 2021; 12: 15947
• 15a Xia W, An Q.-J, Xiang X.-H, Li S, Wang Y.-B, Tan B. Angew. Chem. Int. Ed. 2020; 59: 6775
• 15b Lu D.-L, Chen Y.-H, Xiang S.-H, Yu P, Tan B, Li S. Org. Lett. 2019; 21: 6000
• 16 CCDC 2349792 contains the supplementary crystallographic data for compound 3a. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures
• 17 1-Pyridin-2-ylcarbazoles 3a–x; General Procedure A tube was charged with the appropriate vinylindole 1 (0.1–0.2 mmol, 1.0 equiv), vinylpyridine 2 (0.11–0.22 mmol, 1.1 equiv), catalyst C3 (10–20 mmol%), and chloranil (0.25–0.5 mmol, 2.5 equiv). The tube was then evacuated and refilled three times with N₂. Toluene (2–4 mL) was added, and the mixture was stirred at 40–60 °C for 18–72 h until the reaction was complete (TLC). The mixture was then concentrated under reduced pressure and the residue was purified by column chromatography. Methyl 1-Pyridin-2-yl-9H-carbazole-3-carboxylate (3a) White solid; yield: 93% (0.1 mmol scale) or 94% (5 mmol scale). ¹H NMR (400 MHz, CDCl₃): δ = 11.58 (s, 1 H), 8.72 (s, 1 H), 8.66–8.65 (d, J = 4.4 Hz, 1 H), 8.57 (s, 1 H), 8.06–8.00 (m, 2 H), 7.73–7.69 (m, 1 H), 7.47 (d, J = 8.1 Hz, 1 H), 7.39 (t, J = 7.6 Hz, 1 H), 7.22–7.14 (m, 2 H), 3.91 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 1167.9, 156.89, 148.5, 141.2, 140.2, 136.9, 126.6, 124.6, 124.6, 123.5, 122.9, 121.8, 120.6, 120.6, 120.2, 120.2, 119.4, 111.5, 52.1. HRMS (ESI-ion trap); m/z [M + Na]⁺ calcd for C₁₉H₁₄N₂NaO₂: 325.0953; found: 325.0945.