Copper(I) Mediated IntramolecularCyclization of 2-(2-Amino-phenylethynyl)benzoic and [2-(2-Aminophenylethynyl)phenyl]aceticAcid Esters: A New Synthetic Step towards Isoindolo[2,1-a]indoles and 5H-Indolo[2,1-a]isoquinolines

Francisco J. Reboredo; Mónica Treus; Juan C. Estévez; Luis Castedo; Ramón J. Estévez

doi:10.1055/s-2003-40984

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Synlett 2003(11): 1603-1606
DOI: 10.1055/s-2003-40984

LETTER

Copper(I) Mediated IntramolecularCyclization of 2-(2-Amino-phenylethynyl)benzoic and [2-(2-Aminophenylethynyl)phenyl]aceticAcid Esters: A New Synthetic Step towards Isoindolo[2,1-a]indoles and 5H-Indolo[2,1-a]isoquinolines

Francisco J. Reboredo, Mónica Treus, Juan C. Estévez, Luis Castedo, Ramón J. Estévez*
Departamento de Química Orgánica, Universidade de Santiago de Compostela, 15782Santiago de Compostela, Spain
e-Mail: qorjec@usc.es;

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Publication History

Received 12 June 2003
Publication Date:
05 August 2003 (online)

Abstract
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Abstract

We describe herein parallel synthetic routes to isoindolo[2,1-a]indoles and 5H-indolo[2,1-a]isoquinolines from 2-(2-aminophenylethynyl)benzoicacid esters and [2-(2-aminophenyl-ethynyl)phenyl]aceticacid esters, respectively.

Key words

alkaloids - alkynes - cyclizations - indoles

References

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12

All new compounds gave satisfactoryanalytical and spectroscopic data. Selected physical and spectroscopicdata follow. Compound 5a. Mp 282-284 °C(CH₂Cl₂/MeOH). ¹H NMR(CDCl₃, ppm): δ = 3.87 (s, 3 H, -OCH₃),5.05 (br s, 2 H, -NH₂), 6.65-6.70 (m, 2 H, 2 × Ar-H),7.19 (dt, 1 H, J = 1.5Hz, J = 8.6Hz, Ar-H), 7.34-7.45 (m, 2 H, 2 × Ar-H), 7.53(dt, 1 H, J = 1.4Hz, J = 7.6Hz, Ar-H), 7.70 (dd, 1 H, J = 1.1Hz, J = 7.6Hz, Ar-H), 8.06 (dd, 1 H, J = 1.2Hz, J = 7.9Hz, Ar-H). MS: m/z (%) = 252(6) [M + 1]⁺, 43(100). Compound 5b. Mp 177-180 °C(CH₂Cl₂/MeOH).¹HNMR (CDCl₃, ppm): δ = 3.91 (s, 3 H,-OCH₃), 3.94 (s, 3 H, -OCH₃), 3.97 (s, 3 H,-OCH₃), 5.10 (bs, 2 H, -NH₂), 6.67-6.73(m, 2 H, 2 × Ar-H), 7.09-7.13 (m, 2 H, 2 × Ar-H),7.37 (d, 1 H, J = 7.6 Hz, Ar-H), 7.51(s, 1 H, Ar-H). MS (CI): m/z (%) = 312(100) [M + 1]⁺.Compound 5c. Mp 254-255 ºC (CH₂Cl₂/MeOH). ¹HNMR (CDCl₃, ppm): δ = 3.83 (s, 3 H, -OCH₃),3.87 (s, 3 H, -OCH₃), 3.92 (s, 3 H, -OCH₃),3.95 (s, 3 H, -OCH₃), 3.97 (s, 3 H, -OCH₃),6.29 (s, 1 H, Ar-H), 6.89 (s, 1 H, Ar-H), 7.08 (s, 1 H, Ar-H), 7.51(s, 1 H, Ar-H). MS (CI): m/z (%) = 372(100) [M + 1]⁺. Compound 5d. Mp 125-127 ºC (CH₂Cl₂/MeOH). ¹HNMR (CDCl₃, ppm): δ = 3.69 (s, 3 H,-OCH₃), 3.84 (s, 2 H, -CH₂-), 3.90 (s, 3 H, -OCH₃),3.91 (s, 3 H, -OCH₃), 4.80 (br s, 2 H, -NH₂),6.70-6.73 (m, 2 H, 2 × Ar-H),6.82 (s, 1 H, Ar-H), 7.03 (s, 1 H, Ar-H), 7.13 (dt, 1 H, J = 7.6 Hz, J = 1.2 Hz,Ar-H), 7.35 (dd, 1 H, J = 7.9Hz, J = 1.4Hz, Ar-H). MS: m/z (%) = 326(100) [M + 1]⁺. Compound 5e (oil). ¹H NMR (CDCl₃,ppm): δ = 3.61 (s, 3 H, -OCH₃), 3.68(s, 3 H, -OCH₃), 3.81 (s, 2 H, -CH₂-), 4.44(br s, 2 H, -NH₂), 6.61-6.67 (m, 2H, 2 × Ar-H), 6.74 (dd, 1 H, J = 8.5 Hz, J = 2.4 Hz,Ar-H), 6.82 (d, 1 H, J = 2.4Hz, Ar-H), 7.05 (t, 1 H, J = 7.8Hz, Ar-H), 7.33 (dd, 1 H, J = 8.2Hz, J = 1.3Hz, Ar-H), 7.42 (d, 1 H, J = 8.5Hz, Ar-H). MS (CI): m/z (%) = 296(44) [M + 1]⁺, 19(100). Compound 5f (oil). ¹H NMR (CDCl₃,ppm): δ = 3.66 (s, 3 H, -OCH₃), 3.88(s, 2 H, -CH₂-), 4.43 (br s, 2 H, -NH₂),6.67-6.72 (m, 2 H, 2 × Ar-H),7.12 (dt, 1 H, J = 1.5Hz, J = 8Hz, Ar-H), 7.25-7.37 (m, 4 H, 4 × Ar-H),7.54 (dd, 1 H, J = 2.5 Hz, J = 5.3 Hz,Ar-H). MS (CI): m/z (%) = 266(100) [M + 1]⁺, 234(100). Compound 7a. Mp 149-151 ºC(CH₂Cl₂/MeOH). ¹HNMR (CDCl₃/CD₃SOCD₃, ppm): δ = 6.57(s, 1 H, Ar-H), 7.10-7.49 (m, 6 H, 6 × Ar-H),7.72 (d, 1 H, J = 7.5 Hz,Ar-H), 7.86 (d, 1 H, J = 7.9Hz, Ar-H). MS: m/z (%) = 219(81) [M⁺],163(100). Compound 7b. Mp 177-180 ºC (CH₂Cl₂/MeOH). ¹HNMR (CD₃SOCD₃, ppm): δ = 3.96(s, 3 H, -OCH₃), 4.01 (s, 3 H, -OCH₃), 6.49(s, 1 H, Ar-H), 7.01 (s, 1 H, Ar-H), 7.11 (t, 1 H, J = 7.6Hz, Ar-H), 7.22-7.28 (m, 2 H, 2 × Ar-H),7.41 (d, 1 H, J = 7.6Hz, Ar-H), 7.82 (d, 1 H, J = 7.9Hz, Ar-H). MS: m/z (%) = 279(100) [M⁺]. Compound 7c. Mp 199-201 ºC (CH₂Cl₂/MeOH). ¹HNMR (CDCl₃/CD₃SOCD₃, ppm): δ = 3.91(s, 3 H, -OCH₃), 3.95 (s, 3 H, -OCH₃), 3.98(s, 3 H, -OCH₃), 4.00 (s, 3 H, -OCH₃), 6.37(s, 1 H, Ar-H), 6.90 (s, 1 H, Ar-H), 6.94 (s, 1 H, Ar-H), 7.22 (s,1 H, Ar-H), 7.38 (s, 1 H, Ar-H). MS: m/z (%) = 339 (100) [M⁺].Compound 8a. Mp 180-181 ºC(MeOH). ¹H NMR (CDCl₃, ppm): δ = 3.85(s, 3 H, -OCH₃), 3.89 (s, 2 H, -CH₂-), 3.92(s, 3 H, -OCH₃), 6.53 (s, 1 H, Ar-H), 6.76 (s, 1 H, Ar-H),7.11 (s, 1 H, Ar-H), 7.11-7.29 (m, 2 H, 2 Ar-H), 7.45-7.49(m, 1 H, Ar-H), 8.43-8.47 (m, 1 H, Ar-H). MS: m/z (%) = 293(100) [M⁺]. Compound 8b. Mp 171-172 ºC (CH₂Cl₂/MeOH). ¹HNMR (CDCl₃, ppm): δ = 3.83 (s, 3 H, -OCH₃),4.02 (s, 2 H, -CH₂-), 6.69 (d, 1 H, J = 2.5Hz, Ar-H), 6.83 (s, 1 H, Ar-H), 6.89 (dd, 1 H, J = 8.7Hz, J = 2.5Hz, Ar-H), 7.25-7.32 (m, 2 H, 2 × Ar-H), 7.52-7.54(m, 1 H, Ar-H), 7.71 (d, 1 H, J = 8.7Hz, Ar-H), 8.48-8.52 (m, 1 H, Ar-H). MS: m/z (%) = 263(100) [M⁺].Compound 9. Mp 254-255 ºC(CH₂Cl₂/MeOH). ¹HNMR (CDCl₃/CD₃SOCD₃, ppm): δ = 7.17(s, 1 H, Ar-H), 7.28-7.48 (m, 3 H, 3 × Ar-H), 7.58(d, 1 H, J = 7.2Hz, Ar-H), 7.71 (dt, 1 H, J = 1.1Hz, J = 7.5Hz, Ar-H), 7.85 (d, 1 H, J = 8.0Hz, Ar-H), 8.15 (d, 1 H, J = 8.0Hz, Ar-H), 8.48 (d, 1 H, J = 7.9Hz, Ar-H). MS: m/z (%) = 247(35) [M⁺], 219 (100).