Copper-Catalyzed Synthesis of β- and δ-Carbolines by Double N-Arylation of Primary Amines

Ban Van Phuc; Ha Nam Do; Nguyen Minh Quan; Nguyen Ngoc Tuan; Nguyen Quang An; Nguyen Van Tuyen; Hoang Le Tuan Anh; Tran Quang Hung; Tuan Thanh Dang; Peter Langer

doi:10.1055/s-0040-1720461

Synlett, Table of Contents

Synlett 2021; 32(10): 1004-1008
DOI: 10.1055/s-0040-1720461

letter

Copper-Catalyzed Synthesis of β- and δ-Carbolines by Double N-Arylation of Primary Amines

Ban Van Phuc

^aInstitute of Chemistry, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet, Hanoi, Vietnam

,

Ha Nam Do

^bFaculty of Chemistry, Hanoi University of Science, Vietnam National University (VNU), 19-Le Thanh Tong, Hanoi, Vietnam

,

Nguyen Minh Quan

^cGraduate University of Science and Technology, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet, Hanoi, Vietnam

,

Nguyen Ngoc Tuan

^aInstitute of Chemistry, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet, Hanoi, Vietnam

,

Nguyen Quang An

^aInstitute of Chemistry, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet, Hanoi, Vietnam

,

Nguyen Van Tuyen

^aInstitute of Chemistry, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet, Hanoi, Vietnam

^cGraduate University of Science and Technology, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet, Hanoi, Vietnam

,

Hoang Le Tuan Anh

^dCenter for Research and Technology Transfer, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet, Hanoi, Vietnam

,

Tran Quang Hung ∗

^aInstitute of Chemistry, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet, Hanoi, Vietnam

^cGraduate University of Science and Technology, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet, Hanoi, Vietnam

,

Tuan Thanh Dang∗

^bFaculty of Chemistry, Hanoi University of Science, Vietnam National University (VNU), 19-Le Thanh Tong, Hanoi, Vietnam

,

Peter Langer ∗

^eInstitut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany

^fLeibniz Institut für Katalyse an der Universität Rostock e.V., Albert-Einstein-Str. 3a, 18059 Rostock, Germany

› Author Affiliations

Abstract

All articles of this category

Abstract

Two efficient and practical approaches are reported for the synthesis of β- and δ-carbolines from 3,4-dibromopyridine. The synthesis is based on site-selective Cu-catalyzed double C–N coupling reactions and subsequent annulations by twofold Pd-catalyzed C–N coupling with amines.

Key words

catalysis - heterocycles - cross-coupling - cyclizations - copper

Full Text

References

References and Notes

1a Cao R, Peng W, Wang Z, Xu A. Curr. Med. Chem. 2007; 14: 479
1b Alekseyev RS, Kurkin AV, Yurovskaya MA. Chem. Heterocycl. Compd. 2009; 45: 889
1c Kumar EV, Etukala JR, Ablordeppey SY. Mini.-Rev. Med. Chem. 2008; 8: 538
1d Smirnova OB, Golovko TV, Granik VG. Pharm. Chem. J. 2011; 45: 389

2 Dai J, Dan W, Schneider U, Wang J. Eur. J. Med. Chem. 2018; 157: 622

3a Kobayashi J, Harbour GC, Gilmore J, Rinehart KL. J. Am. Chem. Soc. 1984; 106: 1526
3b Rinehart KL, Kobayashi J, Harbour GC, Hughes RG, Mizsak SA, Scahill TA. J. Am. Chem. Soc. 1984; 106: 1524

4 Sakai R, Higa T, Jefford CW, Bernardinelli G. J. Am. Chem. Soc. 1986; 108: 6404

5a Uredi D, Motati DR, Watkins EB. Org. Lett. 2018; 20: 6336
5b Kumar S, Singh A, Kumar K, Kumar V. Eur. J. Med. Chem. 2017; 142: 48

6a Subbaraju GV, Kavitha J, Rajasekhar D, Jimenez JI. J. Nat. Prod. 2004; 67: 461
6b Paulo A, Gomes ET, Steele J, Warhurst DC, Houghton PJ. Planta Med. 2000; 66: 30
6c Sharaf MH. M, Schiff PL, Tackie AN, Phoebe CH, Johnson RL, Minick D, Andrews CW, Crouch RC, Martin GE. J. Heterocycl. Chem. 1996; 33: 789
6d Yang S.-W, Abdel-Kader M, Malone S, Werkhoven MC. M, Wisse JH, Bursuker I, Neddermann K, Fairchild C, Raventos-Suarez C, Menendez AT, Lane K, Kingston DG. I. J. Nat. Prod. 1999; 62: 976

7a Okamoto T, Akase T, Izumi S, Inaba S, Yamamoto H. JP 7220196, 1972 ; Chem. Abstr. 1972, 152142
7b Winters J, Di Mola N. West German Patent 2442513, 1975 , Chem. Abstr. 1975, 156255

8a Seville S, Phillips RM, Shnyder SD, Wright CW. Bioorg. Med. Chem. 2007; 15: 6353
8b Riechert-Krause F, Eick A, Grunert R, Bednarski PJ, Weisz K. Bioorg. Med. Chem. Lett. 2011; 21: 2380
8c Li B, Yue Z.-Z, Feng J.-M, He Q, Miao Z.-H, Yang C.-H. Eur. J. Med. Chem. 2013; 66: 531
8d Rajanarendar E, Govardhan Reddy K, Ramakrishna S, Nagi Reddy M, Shireesha B, Durgaiah G, Reddy YN. Bioorg. Med. Chem. Lett. 2012; 22: 6677
8e Yin R, Zhang M, Hao C, Wang W, Qiu P, Wan S, Zhang L, Jiang T. Chem. Commun. 2013; 49: 8516
8f Boddupally PV. L, Hahn S, Beman C, De B, Brooks TA, Gokhale V, Hurley LH. J. Med. Chem. 2012; 55: 6076
8g Beauchard A, Jaunet A, Murillo L, Baldeyrou B, Lansiaux A, Chérouvrier J.-R, Domon L, Picot L, Bailly C, Besson T, Thiéry V. Eur. J. Med. Chem. 2009; 44: 3858

9a Rocha e Silva LF, Montoia A, Amorim RC. N, Melo MR, Henrique MC, Nunomura SM, Costa MR. F, Andrade Neto VF, Costa DS, Dantas G, Lavrado J, Moreira R, Paulo A, Pinto AC, Tadei WP, Zacardi RS, Eberlin MN, Pohlit AM. Phytomedicine 2012; 20: 71
9b Van Baelen G, Hostyn S, Dhooghe L, Tapolcsányi P, Mátyus P, Lemière G, Dommisse R, Kaiser M, Brun R, Cos P, Maes L, Hajós G, Riedl Z, Nagy I, Maes BU. W, Pieters L. Bioorg. Med. Chem. 2009; 17: 7209

10 Queiroz M.-JR. P, Ferreira IC. F. R, Gaetano YD, Kirsch G, Calhelha RC, Estevinho LM. Bioorg. Med. Chem. 2006; 14: 6827

11a Sako K, Aoyama H, Sato S, Hashimoto Y, Baba M. Bioorg. Med. Chem. 2008; 16: 3780
11b Peczynska-Czoch W, Pognan F, Kaczmarek L, Boratynski J. J. Med. Chem. 1994; 37: 3503

12a Moon JS, Ahn DH, Kim SW, Lee SY, Lee JY, Kwon JH. RSC Adv. 2018; 8: 17025
12b Im Y, Lee JY. Chem. Commun. 2013; 49: 5948
12c Junyou P, Hong H. WO2018095396A1, 2017

13 Peng H, Chen X, Chen Y, He Q, Xie Y, Yang C. Tetrahedron 2011; 67: 5725
14 Movassaghi M, Hill MD. Org. Lett. 2008; 10: 3485
15 Audia JE, Droste JJ, Nissen JS, Murdoch GL, Evrard DA. J. Org. Chem. 1996; 61: 7937
16 Laha JK, Barolo SM, Rossi RA, Cuny GD. J. Org. Chem. 2011; 76: 6421

17a Shu C, Wang Y.-H, Zhou B, Li X.-L, Ping Y.-F, Lu X, Ye L.-W. J. Am. Chem. Soc. 2015; 137: 9567
17b Nissen F, Richard V, Alayrac C, Witulski B. Chem. Commun. 2011; 47: 6656
17c Li L, Chen X.-M, Wang Z.-S, Zhou B, Liu X, Lu X, Ye L.-W. ACS Catal. 2017; 7: 4004
17d Iwaki T, Yasuhara A, Sakamoto T. J. Chem. Soc., Perkin Trans. 1 1999; 1505
17e Zhang H, Larock RC. J. Org. Chem. 2002; 67: 9318
17f Zhang H, Larock RC. Org. Lett. 2001; 3: 3083
17g Too PC, Chua SH, Wong SH, Chiba S. J. Org. Chem. 2011; 76: 6159
17h Ding S, Shi Z, Jiao N. Org. Lett. 2010; 12: 1540
17i Namjoshi OA, Gryboski A, Fonseca GO, Van Linn ML, Wang Z.-j, Deschamps JR, Cook JM. J. Org. Chem. 2011; 76: 4721
17j Tang S, Wang J, Xiong Z, Xie Z, Li D, Huang J, Zhu Q. Org. Lett. 2017; 19: 5577
17k Alves Esteves CH, Smith PD, Donohoe TJ. J. Org. Chem. 2017; 82: 4435
17l Kamlah A, Lirk F, Bracher F. Tetrahedron 2016; 72: 837
17m Hung TQ, Hieu DT, Van Tinh D, Do HN, Nguyen Tien TA, Van Do D, Son LT, Tran NH, Van Tuyen N, Tan VM, Ehlers P, Dang TT, Langer P. Tetrahedron 2019; 75: 130569
17n Yang C.-C, Tai H.-M, Sun P.-J. J. Chem. Soc., Perkin Trans. 1 1997; 2843
17o Papamicaël C, Quéguiner G, Bourguignon J, Dupas G. Tetrahedron 2001; 57: 5385
17p Mazu TK, Etukala JR, Jacob MR, Khan SI, Walker LA, Ablordeppey SY. Eur. J. Med. Chem. 2011; 46: 2378
17q Detert H, Letessier J. Synthesis 2011; 290
17r Cao J, Xu Y, Kong Y, Cui Y, Hu Z, Wang G, Deng Y, Lai G. Org. Lett. 2012; 14: 38
17s Hung TQ, Dang TT, Janke J, Villinger A, Langer P. Org. Biomol. Chem. 2015; 13: 1375

18 Do HN, Quan NM, Van Phuc B, Van Tinh D, Tien NQ, Nga TT. T, Nguyen VT, Hung TQ, Dang TT, Langer P. Synlett 2021; 32: 611

19a Ma D, Cai Q. Acc. Chem. Res. 2008; 41: 1450
19b Zhang H, Cai Q, Ma D. J. Org. Chem. 2005; 70: 5164

20 Preparation of 3-Bromo-2-(2-bromophenyl)pyridine (1a) 2,3-Dibromopyridine (2.00 g, 8.44 mmol), 2-bromophenyl boronic acid (1.70 g, 8.44 mmol), and Pd(PPh₃)₄ (488 mg, 0.422 mmol) were added to a 250 mL Schlenk flask. The mixture was backfilled several times with argon. To the mixture were added K₂CO₃ (1 M, 25 mL), 5 drops of aqueous KOH (10%) and 35 mL of THF, then backfilled several times with argon. The reaction was heated at 70 °C for 18 h. The solvent was evaporated in vacuo. The residue was extracted with ethyl acetate and water. The organic layer was dried over MgSO₄, filtered, and the solvent was evaporated in vacuo. The yellow residue was purified by column chromatography (silica gel, hexane/ethyl acetate = 20:1) to yield 3-bromo-2-(2-bromophenyl)pyridine (1a)^17s (2.20 g, 85%) as a colorless oil.
21 General Procedure for the Synthesis of 5H-Pyrido[3,2-b]indoles 3a–o 3-Bromo-2-(2-bromophenyl)pyridine (1a, 100 mg, 0.32 mmol), 4-fluoroaniline (116 mg, 0.958 mmol), copper(I) iodide (12 mg, 0.064 mmol, Aldrich, 99%), l-proline (11 mg, 0.096 mmol), and K₂CO₃ (132 mg, 0.958 mmol) were dissolved in DMSO (1.5 mL) and heated at 120 °C for 24 h. After cooling, the reaction mixture was poured into water (50 mL) and extracted with ethyl acetate (3 × 50 mL). The organic layer was dried over MgSO₄, filtered, and the solvent was evaporated in vacuo. The residue was purified by column chromatography (silica gel, hexane/ethyl acetate = 5:1) to yield 5-(4-methylbenzyl)-5H-pyrido[3,2-b]indole (3b, 85 mg, 95%) as a white solid. ¹H NMR (500 MHz, CDCl₃): δ = 8.57 (s, 1 H), 8.46 (s, 1 H), 7.65 (s, 1 H), 7.56–7.50 (m, 1 H), 7.42 (d, J = 8.2 Hz, 1 H), 7.35 (d, J = 6.8 Hz, 2 H), 7.07 (d, J = 7.9 Hz, 2 H), 7.01 (d, J = 7.9 Hz, 2 H), 5.47 (s, 2 H), 2.29 (s, 3 H). ¹³C NMR (126 MHz, CDCl₃): δ = 141.4, 137.5, 133.5, 129.6, 127.9, 126.4, 120.2, 109.3, 21.1. HRMS (ESI): m/z calcd for C₁₉H₁₆N₂ [M + 1]⁺: 273.1386; found: 273.1401.
22 Preparation of 3-Bromo-4-(2-bromophenyl)pyridine (1b) 3,4-Dibromopyridine (2.00 g, 8.44 mmol), 2-bromophenylboronic acid (1.70 g, 8.44 mmol), and Pd(PPh₃)₄ (488 mg, 0.422 mmol) were added to a 250 mL Schlenk flask. The mixture was backfilled several times with argon. To the mixture were added K₂CO₃ (1 M, 25 mL), 5 drops of aqueous KOH (10%), and 35 mL of THF, then backfilled several times with argon. The reaction was heated at 70 °C for 18 h. The solvent was evaporated in vacuo. The residue was extracted with ethyl acetate and water. The organic layer was dried over MgSO₄, filtered, and the solvent was evaporated in vacuo. The residue was purified by column chromatography (silica gel, hexane/ethyl acetate = 20:1) to yield 3-bromo-4-(2-bromophenyl)pyridine (1b)^17m (2.30 g, 80%) as a colorless syrup.
23 General Procedure for the Synthesis of 9H-pyrido[3,4-b]indoles 4a–h 3-Bromo-2-(2-bromophenyl)pyridine (1a, 100 mg, 0.32 mmol), 4-fluoroaniline (116 mg, 0.958 mmol), copper(I) iodide (15.4 mg, 0.08 mmol), l-proline (11 mg, 0.096 mmol), and K₂CO₃ (132 mg, 0.958 mmol) were dissolved in DMSO (1.5 mL) and heated at 160 °C for 24 h. After cooling, the reaction mixture was poured into water (50 mL) and extracted with ethyl acetate (3 × 50 mL). The organic layer was dried over MgSO₄, filtered, and the solvent was evaporated in vacuo. The residue was purified by column chromatography (silica gel, hexane/ethyl acetate = 5:1) to yield 9-phenethyl-9H-pyrido[3,4-b]indole (4e, 61 mg, 70%) as a white solid. ¹H NMR (500 MHz, CDCl₃): δ = 8.72 (s, 1 H), 8.43 (d, J = 4.9 Hz, 1 H), 8.14 (dt, J = 7.9, 1.0 Hz, 1 H), 7.95 (d, J = 5.2 Hz, 1 H), 7.56 (ddd, J = 8.4, 7.1, 1.2 Hz, 1 H), 7.39–7.33 (m, 1 H), 7.32–7.23 (m, 2 H), 7.25–7.20 (m, 1 H), 7.23–7.17 (m, 2 H), 7.17 (ddt, J = 7.7, 5.7, 1.6 Hz, 1 H), 7.11–7.05 (m, 2 H), 4.59 (t, J = 7.4 Hz, 2 H), 3.15 (t, J = 7.4 Hz, 2 H). ¹³C NMR (126 MHz, CDCl₃): δ = 141.1, 138.5, 138.2, 131.7, 128.8, 128.7, 128.7, 128.6, 128.5, 126.9, 126.4, 122.0, 121.1, 119.8, 109.4, 45.3, 35.5. HRMS (ESI): m/z calcd for C₁₉H₁₆N₂ [M + 1]⁺: 273.1386; found: 273.1400.

Supplementary Material

Supporting Information