An Indium(III) Triflate Catalyzed Simple and Efficient One-Pot Synthesis of Substituted 3,3-Diaryloxindoles and Bis(indol-3-yl) methanes from Indoles and Isatins or Aryl Aldehydes

Abstract

Indium(III) triflate was found to be an efficient metal catalyst for the electrophilic substitution reaction of substituted indoles with various isatins or aryl aldehydes in acetonitrile solvent to afford the corresponding 3,3-diaryloxindoles or bis(indol-3-yl)methanes, respectively, in high yields at room temperature. This new procedure has remarkable features such as experimental simplicity, high conversions, good to excellent yields, short reaction times, and simple workup procedures

Key words

indium catalysis - indoles - isatins - aryl aldehydes - diaryloxindoles - bisindolylmethanes

Publikationsverlauf

Eingereicht: 15. Mai 2024

Angenommen nach Revision: 24. Juni 2024

Accepted Manuscript online:
24. Juni 2024

Artikel online veröffentlicht:
15. Juli 2024

• References and Notes

• 1a Ninomiya I. J. Nat. Prod. 1992; 55: 541
• 1b Bolotov VV, Drugovina VV, Yakovleva LV, Bereznyakova AI. Pharm. Chem. J. 1982; 16: 48
• 1c Pajouhesh H, Parsons R, Popp FD. J. Pharm. Sci. 1983; 72: 318
• 2a Joshi KC, Pathak VN, Jain SK. Pharmazie 1980; 35: 677
• 2b Bal TR, Anand B, Yogeeswari P, Sriram D. Bioorg. Med. Chem. Lett. 2005; 15: 4451
• 2c Jiang T, Kuhen KL, Woolf K, Yin H, Bieza K, Caldwell J, Bursulaya B, Tuntland T, Zhang K, Karenewsky D, He Y. Bioorg. Med. Chem. Lett. 2006; 16: 2109
• 2d Maskell L, Blanche EA, Colucci MA, Whatmore JL, Moody CJ. Bioorg. Med. Chem. Lett. 2007; 17: 1575
• 3 Patel GM, Deota PT. Heterocycl. Commun. 2013; 19: 421
• 4 Shaikh MA, Ubale AS, Gnanaprakasam B. Adv. Synth. Catal. 2021; 363: 4876
• 5 Tong J, Huang L.-S, Xu D.-Z. New J. Chem. 2017; 41: 3966
• 6 Liu X, Ma S, Toy PH. Org. Lett. 2019; 21: 9212
• 7 Yuan X, Wang S, Cheng J, Yu B, Liu H.-M. Chin. Chem. Lett. 2020; 31: 2465
• 8 Keshavarz M, Tabatabaee M, Shahabi M, Yazdankish E. Polycyclic Aromat. Compd. 2019; 41: 427
• 9 Azizian J, Mohammadi AA, Karimi AR, Mohammadizadeh MR. J. Chem. Res. 2004; 35: 424
• 10 Azizian J, Mohammadi AA, Karimi N, Mohammadizadeh MR, Karimi AR. Catal. Commun. 2006; 7: 752
• 11 Alimohammadi K, Sarrafi Y, Tajbakhsh M. Monatsh. Chem. 2008; 139: 1037
• 12 Ji S.-J, Zhou M.-F, Gu D.-G, Wang S.-Y, Loh T.-P. Synlett 2003; 2077
• 13 Hazarika P, Sharma SD, Konwar D. Synth. Commun. 2008; 38: 2870
• 14 Mi X, Lu S, He J, Cheng J.-P. Tetrahedron Lett. 2004; 45: 4567
• 15 Chen D, Yu L, Wang PG. Tetrahedron Lett. 1996; 37: 4467
• 16 Bartoli G, Bosco M, Foglia G, Giuliani A, Marcantoni E, Sambri L. Synthesis 2004; 895
• 17 Shi M, Cui S.-C, Li J.-Q. Tetrahedron 2004; 60: 6679
• 18 Wang L, Han J, Tian H, Sheng J, Fan Z, Tang X. Synlett 2005; 337
• 19 Bandgar BP, Shaikh KA. Tetrahedron Lett. 2003; 44: 1959
• 20 Ko S, Lin C, Tu Z, Wang Y.-F, Wang C.-C, Yao C.-F. Tetrahedron Lett. 2006; 47: 487
• 21 Jagannivasan G, Nair GN, Haridas S. Mol. Catal. 2023; 547: 113285
• 22 Katrun P, Atthawalai K, Kuhakarn C. ARKIVOC 2021; (viii) (8) 190
• 23 Mitra B, Ghosh P. ChemistrySelect 2021; 6: 68
• 24a Tsuji H, Yamagata K.-i, Itoh Y, Endo K, Nakamura M, Nakamura E. Angew. Chem. Int. Ed. 2007; 46: 8060
• 24b Endo K, Hatakeyama T, Nakamura M, Nakamura E. J. Am. Chem. Soc. 2007; 129: 5264
• 24c Yu Z, Liu X, Dong Z, Xie M, Feng X. Angew. Chem. Int. Ed. 2008; 47: 1308
• 25a Alapati ML. P. R, Abburin SR, Mukkamala SB, Rao MK. Synth. Commun. 2015; 45: 2436
• 25b Gudla V, Swamy KC, Battula VR. ChemistrySelect 2018; 3: 4576
• 25c Suhasini KP, Praveen KC, Chaguruswamy K, Murthy YL. N. J. Chin. Chem. Soc. (Weinheim, Ger.) 2015; 62: 855
• 25d Mahesh P, Guruswamy K, Diwakar BS, Devi BR, Murthy YL. N, Kollu P, Pammi SV. N. Chem. Lett. 2015; 44: 1386
• 25e Alapati ML. P. R, Abburin SR, Mutyala KR, Makkamala SB. Synth. Commun. 2016; 46: 1242
• 26 1H,1′′H-3,3′:3′,3′′-Terindol-2′(1′H)-one (3a);²⁸ Typical Procedure A mixture of isatin (1a; 1.0 mmol), indole (2a; 2.1 mmol), MeCN (5 ml), and In(OTf)₃ (5 mol%) was stirred at rt in the presence of ambient air until the reaction was complete (TLC). The reaction was then quenched with H₂O (15 mL), and the mixture was extracted with CH₂Cl₂ (3 × 10 mL). The combined organic layers were dried (Na₂SO₄) and concentrated under reduced pressure. The resulting crude product was purified by column chromatography [silica gel, EtOAc–hexanes (3:7)] to give a white solid; yield: 96%; mp 278–281 °C. ¹H NMR (400M Hz, DMSO-d ₆): δ = 10.91 (s, 2 H), 10.57 (s, 1 H), 7.36–7.33 (m, 2 H), 7.27–7.18 (m, 4 H), 7.02–6.98 (t, J = 8.0 Hz, 3 H), 6.93–6.89 (t, J = 8.0 Hz, 3 H), 6.87–6.81 (d, J = 2.0 Hz, 2 H), 6.79–6.77 (m, 2 H). ¹³C NMR (100MHz, DMSO-d ₆): δ = 179.2, 141.8, 137.4, 135.1, 128.3, 126.2, 125.4, 124.7, 121.9, 121.4, 121.2, 118.7, 114.8, 112.1, 110.0, 53.0. 5,5′′,6′-Tribromo-1H,1′′H-3,3′:3′,3′′-terindol-2′(1′H)-one (3o) Yellow solid; yield: 79%; mp 288–290 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 11.28 (s, 2 H), 10.91 (s, 1 H), 7.35 (s, 4 H), 7.17–7.16 (d, J = 6.9 Hz, 3 H), 7.05 (s, 2 H), 6.93 (s, 2 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 178.3, 142.6, 135.8, 132.5, 132.4, 127.1, 126.3, 126.1, 123.7, 122.4, 121.6, 113.9, 113.2, 111.1, 110.0, 51.8. HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₄H₁₄Br₃N₃NaO; 619.8584; found: 619.8581. 6′-Bromo-5,5′′-dichloro-1H,1′′H-3,3′:3′,3′′-terindol-2′(1′H)-one Pink solid; yield: 81%; mp >300 ℃. ¹H NMR (400 MHz, DMSO-d ₆): δ = 11.29 (s, 2 H), 10.90 (s, 1 H), 7.48–7.46 (d, J = 8.0 Hz, 1 H), 7.40–7.17 (m, 7 H), 7.02–6.95 (m, 3 H). ¹³C NMR (100MHz, DMSO-d ₆): δ = 178.5, 141.1, 136.4, 136.2, 131.6, 128.0, 127.5, 126.7, 124.3, 122.9, 114.5, 114.0, 113.5, 112.4, 111.7, 52.9. HRMS (ESI) m/z [M + Na]⁺ calcd for C₂₄H₁₄BrCl₂N₃NaO: 531.9595; found: 531.9593.
• 27 3,3′-(Phenylmethylene)bis-1H-indole (5a);²⁹ Typical Procedure A mixture of PhCHO (1.0 mmol), indole (2a; 2.1 mmol), MeCN (5 mL), and In(OTf)₃ (5 mol%) was stirred at rt in the presence of ambient air until the reaction was complete (TLC). The reaction was then quenched with H₂O (15 mL), and the mixture was extracted with CH₂Cl₂ (3 × 10 mL). The combined organic layers were dried (Na₂SO₄) and concentrated under reduced pressure. The resulting crude product was purified by column chromatography [silica gel, EtOAc–hexanes (3:7)] to give a pink solid; yield: 93%; mp 123–126 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.46 (br s, 2 H), 7.26–7.24 (d, J = 8.0 Hz, 2 H), 7.20–7.18 (d, J = 8.0 Hz, 2 H), 7.14–7.07 (m, 5 H), 7.07–7.00 (t, J = 8.0 Hz, 2 H) 6.89–6.87 (t, J = 8.0 Hz, 2 H), 6.35 (s, 2 H), 5.73 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 143.0, 135.5, 127.6, 127.2, 126.0, 125.1, 122.6, 120.8, 118.8, 118.4, 118.1, 110.0, 39.1. 3,3′-[(4-Fluorophenyl)methylene]bis(4-chloro-1H-indole) (5g) Light-pink solid; yield: 81%; mp 164–166 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.97 (br s, 2 H), 7.43 (s, 2 H), 7.24–7.16 (m, 8 H), 6.56 (s, 2 H), 5.69 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 141.6, 135.3, 132.2, 129.9, 128.6, 128.5, 125.1, 124.8, 122.1, 118.5, 112.8, 39.3. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₃H₁₆Cl₂FN₂: 408.0596; found: 409.0595. 3,3′-[(2,4-Dibromophenyl)methylene]bis-1H-indole (5j) Brown solid; yield: 89%; mp 100–102 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.89 (br s, 2 H), 7.42–7.32 (m, 4 H), 7.18–7.10 (m, 4 H), 7.06–6.99 (m, 4 H), 6.57 (s, 2 H), 6.25 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 140.0, 136.7, 134.6, 132.4, 131.2, 129.3, 127.0, 126.8, 123.8, 122.2, 119.7, 119.4, 117.7, 111.2, 36.3. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₃H₁₇Br₂N₂: 477.9680; found: 478.9682. 3,3′-[(2,5-Dibromophenyl)methylene]bis-1H-indole (5k) Red solid; yield: 86%; mp 158–160 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.77 (br s, 2 H), 7.41–7.39 (d, J = 8.0 Hz, 2 H), 7.28–7.26 (d, J = 8.0 Hz, 2 H), 7.14–7.10 (t, J = 8.0 Hz, 2 H), 6.99–6.96 (m, 2 H), 6.86–6.84 (d, J = 8.0 Hz, 1 H), 6.74–6.68 (m, 2 H), 6.54 (s, 2 H), 6.30 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 153.4, 151.4, 136.7, 134.0, 127.2, 123.5, 121.7, 119.9, 119.3, 119.0, 116.8, 111.8, 110.9, 110.6, 32.1. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₃H₁₇Br₂N₂: 477.9680; found: 478.9683.
• 28 Gupta R, Yadav M, Gaur R, Arora G, Rana P, Yadav P, Adholeya A, Sharma RK. ACS Omega 2019; 4: 21529
• 29 Ramesh C, Banerjee J, Pal R, Das B. Adv. Synth. Catal. 2003; 345: 557