Facile Synthesis of 2-Arylindoles through Plancher-Type Rearrangement of 3-Alkyl-3-Arylindolenines

Santhosh Kumar Chittimalla; Chennakesavulu Bandi; Vinod Kumar Gadi; Siva Ramakrishna Gunturu

doi:10.1055/s-0036-1588448

Synlett, Inhaltsverzeichnis

Synlett 2017; 28(15): 1994-1999
DOI: 10.1055/s-0036-1588448

letter

Facile Synthesis of 2-Arylindoles through Plancher-Type Rearrangement of 3-Alkyl-3-Arylindolenines

Authors

Santhosh Kumar Chittimalla*

Medicinal Chemistry Department, AMRI Singapore Research Centre, 61 Science Park Road, #05-01, The Galen, Science Park II, Singapore 117525, Singapore eMail: santhosh.chittimalla@amriglobal.com eMail: chemcsk@gmail.com
Chennakesavulu Bandi

Medicinal Chemistry Department, AMRI Singapore Research Centre, 61 Science Park Road, #05-01, The Galen, Science Park II, Singapore 117525, Singapore eMail: santhosh.chittimalla@amriglobal.com eMail: chemcsk@gmail.com
Vinod Kumar Gadi

Medicinal Chemistry Department, AMRI Singapore Research Centre, 61 Science Park Road, #05-01, The Galen, Science Park II, Singapore 117525, Singapore eMail: santhosh.chittimalla@amriglobal.com eMail: chemcsk@gmail.com
Siva Ramakrishna Gunturu

Medicinal Chemistry Department, AMRI Singapore Research Centre, 61 Science Park Road, #05-01, The Galen, Science Park II, Singapore 117525, Singapore eMail: santhosh.chittimalla@amriglobal.com eMail: chemcsk@gmail.com

Abstract

Alle Artikel dieser Rubrik

Abstract

3-Alkylindoles on reaction with a cyclohexa-2,4-dien-1-one catalyzed by BF₃·OEt₂ gave the corresponding 3-alkyl-3-arylindolenines in high yields through a tandem Michael addition/aromatization sequence. In the presence of HCl, these indolenine derivatives underwent a facile Plancher-type C-3 to C-2 aryl rearrangement to deliver the corresponding 2-arylindoles.

Key words

arylindoles - indolenines - Plancher rearrangement - cyclohexadienone - tandem reaction

Volltext

Referenzen

References and Notes

1a Kaushik NK. Kaushik N. Attri P. Kumar N. Kim CH. Verma AK. Choi EH. Molecules 2013; 18: 6620
1b Sharma V. Kumar P. Pathak D. J. Heterocycl. Chem. 2010; 47: 491

2a Vicente R. Org. Biomol. Chem. 2011; 9: 6469
2b Taber DF. Tirunahari PK. Tetrahedron 2011; 67: 7195
2c Patil NT. Yamamoto Y. Chem. Rev. 2008; 108: 3395
2d Humphrey GR. Kuethe JT. Chem. Rev. 2006; 106: 2875

3a Djakovitch L. Batail N. Genelot M. Molecules 2011; 16: 5241
3b Simonetti M. Cannas DM. Panigrahi A. Kujawa S. Kryjewski M. Xie P. Larrosa I. Chem. Eur. J. 2017; 23: 549

4a Lebrasseur N. Larrosa I. Adv. Heterocycl. Chem. 2012; 105: 309
4b Joucla L. Djakovitch L. Adv. Synth. Catal. 2009; 351: 673

5 Rossi R. Lessi M. Manzini C. Marianetti G. Bellina F. Tetrahedron 2016; 72: 1795

6a Xu H. Mini-Rev. Org. Chem. 2009; 6: 367
6b Monnier F. Taillefer M. Angew. Chem. Int. Ed. 2009; 48: 6954
6c Old DW. Harris MC. Buchwald SL. Org. Lett. 2000; 2: 1403
6d Hartwig JF. Kawatsura M. Hauck SI. Shaughnessy KH. Alcazar-Roman LM. J. Org. Chem. 1999; 64: 5575

For metal free N-arylations see:

6e Xu H. Fan L.-L. Z. Naturforsch., B 2008; 63: 298
6f Smith WJ. III. Sawyer JS. Heterocycles 1999; 51: 157
6g Maiorana S. Baldoli C. Del Buttero P. Di Ciolo M. Papagni A. Synthesis 1998; 735

For C3-arylation, see:

7a Vásquez-Céspedes S. Chepiga KM. Möller N. Schäfer AH. Glorius F. ACS Catal. 2016; 6: 5954
7b Pitts AK. O’Hara F. Snell RH. Gaunt MJ. Angew. Chem. Int. Ed. 2015; 54: 5451
7c Phipps RJ. Grimster NP. Guant MJ. J. Am. Chem. Soc. 2008; 130: 8172

For C2-arylation, see

7d Duan L. Fu R. Zhang B. Shi W. Chen S. Wan Y. ACS Catal. 2016; 6: 1062
7e Malmgren J. Nagendiran A. Tai C.-W. Bäckvall J.-E. Olofsson B. Chem. Eur. J. 2014; 20: 13531
7f Ibañez S. Oresmaa L. Estevan F. Hirva P. Sanaú M. Úbeda MA. Organometallics 2014; 33: 5378
7g Tang D.-TD. Collin KD. Ernst JB. Glorius F. Angew. Chem. Int. Ed. 2014; 53: 1809
7h Deprez NR. Kalyani D. Krause A. Sanford MS. J. Am. Chem. Soc. 2006; 128: 4972

For C3-arylation, see:

8a Joucla L. Batail N. Djakovitch L. Adv. Synth. Catal. 2010; 352: 2929
8b Bellina F. Benelli F. Rossi R. J. Org. Chem. 2008; 73: 5529
8c Zhang Z. Hu Z. Yu Z. Lei P. Chi H. Wang Y. He R. Tetrahedron Lett. 2007; 48: 2415

For C2-arylation, see Ref. 8 (a) and:

8d Lane BS. Brown MA. Sames D. J. Am. Chem. Soc. 2005; 127: 8050
8e Wang X. Lane BS. Sames D. J. Am. Chem. Soc. 2005; 127: 4996
8f Xu Z. Xu Y. Lu H. Yang T. Lin X. Shao L. Ren F. Tetrahedron 2015; 71: 2616
8g Islam S. Larrosa I. Chem. Eur. J. 2013; 19: 15093

For C3-arylation, see:

9a Yamaguchi K. Kondo H. Yamaguchi J. Itami K. Chem. Sci. 2013; 4: 3753

For C2-arylation, see:

9b Yang S.-D. Sun C.-L. Fang Z. Li B.-J. Li Y.-Z. Shi Z.-J. Angew. Chem. Int. Ed. 2008; 47: 1473
9c Zhang L. Li P. Liu C. Yang J. Wang M. Wang L. Catal. Sci. Technol. 2014; 4: 1979

10 For C2-arylation, see: Zhao J. Zhang Y. Cheng K. J. Org. Chem. 2008; 73: 7428
11 For C2-arylation, see: Li Z. Zhou H. Xu J. Wu X. Yao H. Tetrahedron 2013; 69: 3281
12 For C2-arylation, see: Liang Z. Yao B. Zhang Y. Org. Lett. 2010; 12: 3185
13 For C2-arylation, see: Liu C. Ding L. Guo G. Liu W. Yang F.-L. Org. Biomol. Chem. 2016; 14: 2824
14 For C2-arylation, see: Miao T. Li P. Wang G.-W. Wang L. Chem. Asian J. 2013; 8: 3185

15a Ye Y. Wang H. Fan R. Synlett 2011; 923
15b Yadav JS. Reddy BV. S. Shankar KS. Swamy T. Premalatha K. Bull. Korean Chem. Soc. 2008; 29: 1418
15c Hsieh MF. Rao PD. Liao C.-C. Chem. Commun. 1999; 1441

For the synthesis of 3-arylindoles by ClO₄/SiO₂ catalyzed reaction of cyclohexa-2,4-dien-1-ones and 3-unsubstituted indoles, see:

15d Chittimalla SK. Bandi C. Putturu S. Kuppusamy R. Boellaard KC. Tan DC. A. Lum DM. J. Eur. J. Org. Chem. 2014; 2565

16 Parumala SK. R. Peddinti RK. Org. Lett. 2013; 15: 3546
17 See Supporting Information.

For indole C-3 to C-2 alkyl migration furnishing 2-alkylated indoles see:

18a Wu Q.-F. Zhen C. Zhuo C.-X. You S.-L. Chem. Sci. 2016; 7: 4453
18b Mari M. Lucarini S. Bartoccini F. Piersanti G. Spadoni G. Beilstein J. Org. Chem. 2014; 10: 1991
18c Bajtos B. Yu M. Zhao H. Pagenkopf BL. J. Am. Chem. Soc. 2007; 129: 9631

For indole C-3 to C-2 aryl migration furnishing 2-arylindole derivatives see:

18d Chai Z. Chen J.-N. Liu Z. Li X.-F. Yang P.-J. Hu J.-P. Yang G. Org. Biomol. Chem. 2016; 14: 1024
18e Zhu S. MacMillan DW. C. J. Am. Chem. Soc. 2012; 134: 10815

For indole C-3 arylation with masked; p-benzoquinones see:

18f Shu C. Liao L.-H. Liao Y.-J. Hu X.-Y. Zhang Y.-H. Yuan W.-C. Zhang X.-M. Eur. J. Org. Chem. 2014; 4467

19 BF₃·OEt₂-Catalyzed Reaction of a Cyclohexadienone and an Alkylindole; Typical Procedure BF₃·OEt₂ (0.067 mL, 0.54 mmol) was added to a stirred solution of cyclohexadienone 1a (100 mg, 0.54 mmol) and skatole (2a; 71 mg, 0.54 mmol) in CH₂Cl₂ (2.0 mL) at –78 °C, and the mixture was stirred at –78 °C for 3 h. MeOH (2 mL) was added and the mixture was stirred for 30 min. The solvent was removed by rotary evaporation, and the crude residue was purified by flash column chromatography (silica gel, 0–30% EtOAc–hexanes) to give 3aa (62 mg, 27%), 3aa′′ (55 mg, 24%) and 3aa′ (30 mg, 13%), along with inseparable mixture of other uncharacterized products. 2,3-Dimethoxy-5-(3-methyl-1H-indol-2-yl)phenol (3aa) ¹H NMR (400 MHz, CDCl₃): δ = 7.98 (br s, 1 H), 7.60–7.57 (m, 1 H), 7.37–7.34 (m, 1 H), 7.24–7.18 (m, 1 H), 7.17–7.12 (m, 1 H), 6.82 (d, J = 2.0 Hz, 1 H), 6.68 (d, J = 2.0 Hz, 1 H), 5.89 (br, s 1 H), 3.97 (s, 3 H), 3.93 (s, 3 H), 2.46 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 152.5 (C), 149.5 (C), 135.7 (C), 135.0 (C), 133.8 (C), 130.0 (C), 129.4 (C), 122.3 (CH), 119.5 (CH), 118.9 (CH), 110.6 (CH), 108.5 (C), 107.6 (CH), 104.0 (CH), 61.1 (CH₃), 56.0 (CH₃), 9.7 (CH₃). ESI-MS: m/z = 284 [C₁₇H₁₇NO₃ + H]⁺. 2,3-Dimethoxy-5-(3-methyl-3H-indol-3-yl)phenol (3aa′) ¹H NMR (400 MHz, CDCl₃): δ = 8.09 (s, 1 H), 7.66 (app d, J = 8.0 Hz, 1 H), 7.40–7.34 (m, 1 H), 7.28–7.27 (m, 2 H), 6.56 (d, J = 2.0 Hz, 1 H), 5.79, (s, 1 H), 6.12 (d, J = 2.0 Hz, 1 H), 3.86 (s, 3 H), 3.73 (s, 3 H), 1.68 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 178.1 (CH), 154.3 (C), 152.5 (C), 149.6 (C), 144.5 (C), 135.0 (C), 134.0 (C), 128.1 (CH), 126.7 (CH), 122.5 (CH), 121.4 (CH), 106.4 (CH), 102.1 (CH), 61.1 (CH₃), 60.8 (C), 55.8 (CH₃), 20.2 (CH₃). ESI-MS: m/z = 284 [C₁₇H₁₇NO₃ + H]⁺. 2,3-Dimethoxy-5-(3-methyl-1H-indol-1-yl)phenol (3aa′′) ¹H NMR (400 MHz, CDCl₃): δ = 7.63–7.56 (m, 2 H), 7.25–7.14 (m, 2 H), 7.09 (app q, J = 1.2 Hz, 1 H), 6.74 (d, J = 2.4 Hz, 1 H), 6.60 (d, J = 2.4 Hz, 1 H), 5.93 (s, 1 H), 3.96 (s, 3 H), 3.89 (s, 3 H), 2.38 (d, J =1.2 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 152.8 (C), 149.8 (C), 136.2 (C), 136.0 (C), 133.7 (C), 129.7 (C), 125.5 (CH), 122.3 (CH), 119.7 (CH), 119.2 (CH), 112.6 (C), 110.5 (CH), 104.1 (CH), 100.7 (CH), 61.1 (CH₃), 56.1 (CH₃), 9.5 (CH₃). ESI-MS m/z 284 [C₁₇H₁₇NO₃ + H]⁺. Methyl 4-[3-(3-Hydroxy-4,5-dimethoxyphenyl)-3H-indol-3-yl]butanoate (3ac′); Typical Procedure A freshly prepared stock solution of BF₃·Et₂O (0.3 mL, 0.54 mmol, 1 mL) in CH₂Cl₂ (4 mL) was added to stirred solution of cyclohexadienone 1a (100 mg, 0.54 mmol) and methyl 4-(1H-indol-3-yl)butanoate (2c; 120 mg, 0.54 mmol) in CH₂Cl₂ (2.5 mL) at 0 °C, and the mixture was stirred for 30 min. The mixture was then diluted with sat. aq NH₄Cl (10 mL) and extracted with CH₂Cl₂ (3 × 20 mL). The extracts were concentrated by rotary evaporation and the crude product was purified by column chromatography (silica gel, 0–70% EtOAc–hexane) to give a brown solid; yield: 180 mg (90%). ¹H NMR (400 MHz, CDCl₃): δ = 8.14 (s, 1 H), 7.66 (d, J = 7.6 Hz, 1 H), 7.40–7.27 (m, 3 H), 6.58 (d, J = 2.0 Hz, 1 H), 6.22 (d, J = 2.0 Hz, 1 H), 5.82 (br s, 1 H), 3.85 (s, 3 H), 3.75 (s, 3 H), 3.62 (s, 3 H), 2.26–2.17 (m, 4 H), 1.53–1.47 (m, 1 H), 1.32–1.26 (m, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 177.0 (CH), 173.3 (C), 154.9 (C), 152.6 (C), 149.7 (C), 142.0 (C), 135.0 (C), 133.2 (C), 128.2 (CH), 126.6 (CH), 123.2 (CH), 121.5 (CH), 106.8 (CH), 102.5 (CH), 65.2 (C), 60.8 (CH₃), 55.9 (CH₃), 51.5 (CH₃), 34.3 (CH₂), 33.8 (CH₂), 19.9 (CH₂). ESI-MS: m/z = 370 [C₂₁H₂₃NO₅ + H]⁺. 5-(3,5-Dimethyl-1H-indol-2-yl)-2,3-dimethoxyphenol (3ah); Typical Procedure A freshly prepared stock solution of BF₃·Et₂O (0.3 mL, 0.54 mmol, 1 mL) in CH₂Cl₂ (4 mL) was added to stirred solution of cyclohexadienone 1a (100 mg, 0.54 mmol) and 3,5-dimethyl-1H-indole (2h, 79 mg, 0.54 mmol) in CH₂Cl₂ (2.5 mL) at 0 °C, and the mixture was stirred for 30 min, the solvent was removed to give a residue. The residue was then diluted with 2 N aq HCl (10 mL) and stirred for 2–6 h (16 h for reactions of indole 2e). The mixture was extracted with EtOAc (3 × 20 mL), and the extracts were dried (Na₂SO₄), filtered, and concentrated in vacuo. The crude product was purified by column chromatography (silica gel, 0–70% EtOAc–hexane) to give a reddish solid; yield: 131 mg (82%). ¹H NMR (400 MHz, CDCl₃): δ = 7.87 (br s, 1 H), 7.37 (br s, 1 H), 7.24 (d, J = 8.0 Hz, 1 H), 7.03 (dd, J = 8.0, 1.2 Hz, 1 H), 6.81 (d, J = 1.6 Hz, 1 H), 6.67 (d, J = 1.6 Hz, 1 H), 5.89 (br s, 1 H), 3.96 (s, 3 H), 3.93 (s, 3 H), 2.48 (s, 3 H), 2.44 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 152.5 (C), 149.5 (C), 134.9 (C), 134.0 (C), 133.9 (C), 130.0 (C), 129.6 (C), 128.8 (C), 123.9 (CH), 118.6 (CH), 110.3 (CH), 108.1 (C), 107.5 (CH), 104.0 (CH), 61.1 (CH₃), 56.0 (CH₃), 21.5 (CH₃), 9.6 (CH₃). ESI-MS: m/z 298 [C₁₈H₁₉NO₃ + H]⁺.
20 Even with N-substituted indoles 2i–k as substrates, it appeared that C-3-arylation occurred first, and only after HCl treatment did these reaction mixtures become cleaner for isolation. We found that a prolonging reaction time under BF₃·OEt₂-catalyzed condition for the Plancher-type rearrangement was not suitable for delivering 2-arylindole derivatives. Under these conditions, 2-arylindoles were obtained in low yields together with uncharacterized product mixtures.

Zusatzmaterial

Supporting Information (PDF)