HI/DMSO-Based Chemoselective Oxidative Halogenation of Pyrrolo[2,1-a]isoquinolines

Abstract

The application of HI in DMSO-based modifications of pyrrolo[2,1-a]isoquinoline derivatives has been explored. Selective chlorinations and iodinations of pyrrolo[2,1-a]isoquinolines have been achieved by using a HI/DMSO-based reaction system. A chlorination/aromatization cascade can be achieved by performing the reaction at 150 °C with NiCl₂ as a chlorine source, whereas an iodination product was obtained by carrying out the reaction in PhCl/DMSO with HI at a lower temperature. Furthermore, it was found that the chemoselectivity can be tuned by the use of various additives, thereby providing methylthiolated or formylated pyrrolo[2,1-a]isoquinoline derivatives in acceptable yields.

Key words

chlorination - dimethyl sulfoxide - hydrogen iodide - iodination - pyrroloisoquinolines

Publikationsverlauf

Eingereicht: 26. November 2024

Angenommen nach Revision: 24. Dezember 2024

Accepted Manuscript online:
24. Dezember 2024

Artikel online veröffentlicht:
27. Januar 2025

• References and Notes

• 1a Cresswell AJ, Eey ST.-C, Denmark SE. Angew. Chem. Int. Ed. 2015; 54: 15642
• 1b Petrone DA, Ye J, Lautens M. Chem. Rev. 2016; 116: 8003
• 1c Podgoršek A, Zupan M, Iskra J. Angew. Chem. Int. Ed. 2009; 48: 8424
• 1d Das R, Kapur M. Asian J. Org. Chem. 2018; 7: 1524
• 1e Wang W, Song S, Jiao N. Acc. Chem. Res. 2024; 57: 3161
• 2a Gribble GW. Acc. Chem. Res. 1998; 31: 141
• 2b Hernandes MZ, Cavalcanti SM. T, Moreira DR. M, de Azevedo WF. Jr, Leite AC. L. Curr. Drug Targets 2010; 11: 303
• 2c Auffinger P, Hays FA, Westhof E, Ho PS. Proc. Natl. Acad. Sci. U. S. A. 2004; 101: 16789
• 3 Li JJ. Name Reactions: A Collection of Detailed Mechanisms and Synthetic Applications, 4th ed. Springer eBooks; Berlin: 2009
• 4a Palani V, Perea MA, Sarpong R. Chem. Rev. 2022; 122: 10126
• 4b Dubost E, McErlain H, Babin V, Sutherland A, Cailly T. J. Org. Chem. 2020; 85: 8300
• 5a Eckelman WC, Adams HR, Paik CH. Int. J. Nucl. Med. Biol. 1984; 11: 163
• 5b Stavber S, Jereb M, Zupan M. Synthesis 2008; 1487
• 5c Artaryan A, Mardyukov A, Kulbitski K, Avigdori I, Nisnevich GA, Schreiner PR, Gandelman M. J. Org. Chem. 2017; 82: 7093
• 5d Racys R, Sharif SA. I, Pimlott SL, Sutherland A. J. Org. Chem. 2016; 81: 772
• 5e Hanson JR. J. Chem. Res. 2006; 277
• 5f Ajvazi N, Stavber S. Compounds 2022; 2: 3
• 5g Chand D., He C., Mitchell L. A., Parrish D. A.: Shreeve JM. Dalton Trans. 2016; 45: 13827
• 6a Zielinska A, Skulski L. Molecules 2005; 10: 1307
• 6b Tanwar L, Börgel L, Lehmann J, Ritter T. Org. Lett. 2021; 23: 5024
• 6c Zheng T, Xu J, Cheng S, Ye J, Ma S, Tong R. J. Org. Chem. 2023; 88: 11497
• 6d Semwal R, Ravi C, Meena R, Adimurthy S. J. Org. Chem. 2019; 84: 792
• 7 Podgoršek A, Zupan M, Iskra J. Angew. Chem. Int. Ed. 2009; 48: 8424
• 8a Wu X.-F, Natte K. Adv. Synth. Catal. 2016; 358: 336
• 8b Kaiser D, Klose I, Oost R, Neuhaus J, Maulide N. Chem. Rev. 2019; 119: 8701
• 8c Smith LH. S, Coote SC, Sneddon HF, Procter DJ. Angew. Chem. Int. Ed. 2010; 49: 5832
• 8d Jones-Mensah E, Karki M, Magolan J. Synthesis 2016; 48: 1421
• 9a Xue W.-J, Li Q, Zhu Y.-P, Wang J.-G, Wu A.-X. Chem. Commun. 2012; 48: 3485
• 9b Zheng T, Li Z, Luo Y, Zhang J, Xu J. Tetrahedron 2023; 133: 133274
• 9c Deshidi R, Devari S, Shah BA. Eur. J. Org. Chem. 2015; 1428
• 9d Zhu X, Yang Y, Xiao G, Song J, Liang Y, Deng G. Chem. Commun. 2017; 53: 11917
• 9e Tang M, Wang Y.-X, Huang S, Xie L.-G. Org. Chem. Front. 2023; 10: 2416
• 10a Majetich G, Hicks R, Reister S. J. Org. Chem. 1997; 62: 4321
• 10b Ebule R, Hammond GB, Xu B. Eur. J. Org. Chem. 2018; 4705
• 10c Tong H, Chen C, Liu W, Pan Y, Duan L. Asian J. Org. Chem. 2019; 8: 479
• 10d Sorabad GS, Maddani MR. New J. Chem. 2019; 43: 6563
• 10e Zheng T, Li Z, Luo Y, Zhang J, Xu J. Tetrahedron 2023; 133: 133274
• 11a Song S, Sun X, Li X, Yuan Y, Jiao N. Org. Lett. 2015; 17: 2886
• 11b Li X, Song S, Jiao N. Acta Chim. Sinica 2017; 75: 1202
• 12 Dalai PG, Palit K, Panda N. Adv. Synth. Catal. 2022; 364: 1031
• 13a Karki M, Magolan J. J. Org. Chem. 2015; 80: 3701
• 13b Mal K, Kaur A, Haque F, Das I. J. Org. Chem. 2015; 80: 6400
• 13c Song S, Li X, Sun X, Yuan Y, Jiao N. Green Chem. 2015; 17: 3285
• 13d Li H.-L, An X.-L, Ge L.-S, Luo X, Deng W.-P. Tetrahedron 2015; 71: 3247
• 13e Liu C, Dai R, Yao G, Deng Y. J. Chem. Res. 2014; 38: 593
• 13f Zoretic PA. J. Org. Chem. 1975; 40: 1867
• 13g Rezaei N, Ranjbar PR. Tetrahedron Lett. 2018; 59: 4102
• 13h Sorabad GS, Maddani MR. Asian J. Org. Chem 2019; 8: 1336
• 13i Wang H, Li Z, Dai R, Jiao N, Song S. Chem. Sci. 2023; 14: 13228
• 14 Cui H.-L. Org. Biomol. Chem. 2024; 22: 1580
• 15a Zhu Y.-p, Liu M.-c, Jia F.-c, Yuan J.-j, Gao Q.-h, Lian M, Wu A.-x. Org. Lett. 2012; 14: 3392
• 15b Singh D, Chowdhury SR, Pramanik S, Maity S. Tetrahedron 2021; 88: 132125
• 15c Bodhak C, Pramanik A. J. Org. Chem. 2019; 84: 7265
• 15d Yang D.-S, Chen X.-L, Wu A.-X. Org. Chem. Front. 2024; 11: 2665
• 16 Ma J.-T, Wang L.-S, Chai Z, Chen X.-F, Tang B.-C, Chen X.-L, He C, Wu Y.-D, Wu A.-X. Chem. Commun. 2021; 57: 5414
• 17 Cui H.-L, Chen X.-H. J. Org. Chem. 2023; 88: 11935
• 18 Zhou J, Huang X, Yu X, Yang L, Han J.-Y, Lhazom T, Cui H.-L. J. Org. Chem. 2024; 89: 9789
• 19 Li Y.-M, Jiang M, Zhou J, Cui H.-L. Asian J. Org. Chem 2024; e202400323
• 20a Song S, Li X, Wei J, Wang W, Zhang Y, Ai L, Zhu Y, Shi X, Zhang X, Jiao N. Nat. Catal. 2020; 3: 107
• 20b Cernak T, Dykstra KD, Tyagarajan S, Vachalb P, Krska SW. Chem. Soc. Rev. 2016; 45: 546
• 20c Cui H.-L. Targets Heterocycl. Syst. 2022; 26: 222
• 21a Fan H, Peng J, Hamann MT, Hu JF. Chem. Rev. 2008; 108: 264
• 21b Bailly C. Mar. Drugs 2015; 13: 1105
• 21c Fukuda T, Ishibashi F, Iwao M. Alkaloids (San Diego, CA U. S.) 2020; 83: 1
• 21d Matveeva MD, Purgatorio R, Voskressensky LG, Altomare CD. Future Med. Chem. 2019; 11: 2735
• 21e Pässler U, Knölker H.-J. Alkaloids (San Diego, CA U. S.) 2011; 70: 79
• 21f Fukuda T, Ishibashi F, Iwao M. Heterocycles 2011; 83: 491
• 21g Banwell M, Lan P. Targets Heterocycl. Syst. 2020; 24: 208
• 21h Cui H.-L. Org. Biomol. Chem. 2022; 20: 2779
• 22a Zhao W, Xie P, Bian Z, Zhou A, Ge H, Zhang M, Ding Y, Zheng L. J. Org. Chem. 2015; 80: 9167
• 22b Zhang L.-Y, Wu Y.-H, Wang N.-X, Gao X.-W, Yan Z, Xu B.-C, Liu N, Wang B.-Z, Xing Y.-L. Eur. J. Org. Chem. 2021; 2021: 1446
• 23a Fei H, Yu J, Jiang Y, Guo H, Cheng J. Org. Biomol. Chem. 2013; 11: 7092
• 23b Wang Y.-F, Zhang F.-L, Chiba S. Synthesis 2012; 44: 1526
• 23c Li J.-Q, Tan H.-L, Ma D.-D, Zhu X.-X, Cui H.-L. J. Org. Chem. 2021; 86: 10118
• 23d Huang X, Zhou J, Pei S.-C, Cui H.-L. J. Org. Chem. 2024; 89: 6353
• 23e Cao H, Lei S, Li N, Chen L, Liu J, Cai H, Qiu S, Tan J. Chem. Commun. 2015; 51: 1823
• 23f Xiang S, Chen H, Liu Q. Tetrahedron Lett. 2016; 57: 3870
• 23g Qian J, Zhang Z, Liu Q, Liu T, Zhang G. Adv. Synth. Catal. 2018; 360: 1199
• 23h Wang Y, Liu X.-F, He W.-M. Org. Chem. Front. 2023; 10: 4198
• 23i Bhattacharjee S, Laru S, Ghosh P, Hajra A. J. Org. Chem. 2021; 86: 10866
• 23j Wu X.-F, Neumann H, Beller M. Chem. Rev. 2013; 113: 1
• 23k Yao S.-J, Ren Z.-Z, Guan Z.-H. Tetrahedron Lett. 2016; 57: 3892
• 24 Intermediate 6a′ has been detected by HRMS. HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₇H₂₉ClN₂NaO₅: 519.1657; found: 519.1666.
• 25 Kornblum N, Jones WJ, Anderson GJ. J. Am. Chem. Soc. 1959; 81: 4113
• 26 Chen X.-H, Cui H.-L. J. Org. Chem. 2023; 88: 7347
• 27a Shi Y, Wong J, Ke Z, Yeung Y.-Y. J. Org. Chem. 2019; 84: 4017
• 27b Yoshimura G, Sakamoto J, Kitajima M, Ishikawa H. Chem. Eur. J. 2024; e202401153
• 28a Li L, Liu W, Mu X, Mi Z, Li C.-J. Nat. Protoc. 2016; 11: 1948
• 28b Sloan NL, Luthra SK, McRobbie G, Pimlott SL, Sutherland A. RSC Adv. 2017; 7: 54881
• 29 CCDC 2363337, 2387695, and 2365622 contain the supplementary crystallographic data for compounds 1a, 2a, and 5a, respectively. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures
• 30a Ashikari Y, Shimizu A, Nokami T, Yoshida J.-i. J. Am. Chem. Soc. 2013; 135: 16070
• 30b Panda N, Palit K, Mohapatra S. Org. Biomol. Chem. 2024; 22: 7103
• 31 Compounds 2a–n, 1a, and 4aa; General Procedure 55% aq HI (41.0 μL, 0.3 mmol) was added to a mixture of the appropriate pyrrolo[2,1-a]isoquinoline S1 (0.1 mmol, 1.0 equiv) and NiCl₂·6 H₂O (0.5 equiv, 11.9 mg) in DMSO (0.1 M) at r.t., and the resulting mixture was stirred at 150 °C (oil bath) for the time indicated in Scheme 3. The mixture was then cooled to r.t., diluted with CH₂Cl₂ (3 mL), washed with sat. aq Na₂SO₃ (2 mL) and H₂O (3 × 2 mL), and then dried (Na₂SO₄). The organic phase was purified directly by flash chromatography (silica gel, hexane–EtOAc). Methyl 3-Chloro-1-(4-chlorophenyl)-8,9-dimethoxypyrrolo[2,1-a]isoquinoline-2-carboxylate (2a) Purified by a flash chromatography [silica gel, hexane–EtOAc] as a pale-yellow solid; yield: 28.7 mg, 67%. ¹H NMR (400 MHz, CDCl₃): δ = 7.87 (d, J = 7.5 Hz, 1 H), 7.51–7.44 (m, 2 H), 7.41–7.34 (m, 2 H), 6.95 (s, 1 H), 6.87 (d, J = 7.5 Hz, 1 H), 6.70 (s, 1 H), 3.92 (s, 3 H), 3.71 (s, 3 H), 3.42 (s, 3 H). ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 164.0, 149.3, 148.5, 135.0, 133.4, 132.7, 128.5, 125.5, 121.4, 120.2, 118.6, 115.8, 113.7, 113.6, 112.8, 108.1, 104.5, 55.9, 55.1, 51.3. HRMS (ESI): m/z [M + H]⁺ Calcd for C₂₂H₁₈Cl₂NO₄: 430.0607; found: 430.0627.