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DOI: 10.1055/s-2003-40984
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
Publikationsverlauf
Publikationsdatum:
05. August 2003 (online)
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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
-
1a
Hegedus LS. Angew. Chem., Int.Ed. Engl. 1989, 27: 1113 -
1b
Saxton JE. Nat. Prod. Rep. 1996, 13: 327 -
1c
Ihara M.Fukumoto K. Nat. Prod. Rep. 1997, 14: 413 -
1d
Hiroya K.Suzuki N.Yasuhara A.Egawa Y.Kasano A.Sakamoto T. J. Chem. Soc., Perkin Trans. 1 2000, 4339 ; and references cited therein -
2a
Scartoni V.Morelli I.Marsili A.Catalano S. J. Chem.Soc., Perkin Trans. 1 1977, 2332 -
2b
Scartoni V.Tognetti T. J. Heterocycl. Chem. 1984, 21: 1499 -
2c
Hooper M.Imam SH. J. Chem. Soc., PerkinTrans. 1 1985, 1583 -
2d
Xiong Y.Moore HW. J. Org. Chem. 1996, 61: 9168 -
3a
Kanaoka Y.Koyama K. TetrahedronLett. 1972, 4517 -
3b
Kanaoka Y.Nagasawa C. Heterocycles 1975, 3: 553 -
3c
Terashima M.Koyama K.Kanoka Y. Chem.Pharm. Bull. 1978, 26: 630 -
3d
Kanaoka Y.Koyama K.Hatanaka Y. J.Photochem. 1985, 28: 575 -
3e
Carruthers W.Evans N. J. Chem. Soc., Perkin Trans.1 1974, 1523 - 4
Caddick S.Aboutayab K.Jenkins K.West RI. J. Chem. Soc., PerkinTrans. 1 1996, 675 - 5
Kraus GA.Kim H. Synth. Commun. 1993, 23: 55 -
6a
Itahara T. Synthesis 1978, 607 -
6b
Itahara T. Synthesis 1979, 151 -
6c
Itahara T. Chem.Lett. 1982, 1151 -
6d
Itahara T.Ikeda M.Sakakibara T. J.Chem. Soc., Perkin Trans. 1 1983, 1361 -
6e
Itahara T. Heterocycles 1986, 2557 -
6f
Grigg R.Sridharan V.Stevenson P.Sukirthalingam S.Worakun T. Tetrahedron 1990, 46: 4003 -
6g
Kozikowski AP.Ma D. Tetrahedron Lett. 1991, 32: 3317 -
6h
Desarbre E.Merour J. Heterocycles 1995, 1987 -
7a
Gribble GW. In ComprehensiveHeterocyclic Chemistry II Vol. 2:Katritzky AR.Rees CW.Scriven EFV. PergamonPress; Oxford: 1996. p.207 -
7b
Gribble GW. J. Chem. Soc., Perkin Trans. 1 2000, 1045 - 8
Rudisill DE.Stille JK. J. Org. Chem. 1989, 54: 5856 -
9a
Yu MS.Leon LL.McGuire MA.Botha G. TetrahedronLett. 1998, 39: 9347 -
9b
Sakamoto T.Kondo Y.Iwashita S.Nagano T.Yamanaka H. Chem.Pharm. Bull. 1988, 36: 1305 -
10a
Iritani K.Matsubara S.Uchimoto K. Tetrahedron Lett. 1988, 29: 1799 -
10b
Arcadi A.Cacchi S.Marinelli F. TetrahedronLett. 1989, 30: 2581 -
10c
Cacchi S.Carnicelli V.Marinelli F. J.Organomet. Chem. 1994, 475: 289 -
10d
McDonald FE.Chatterjee AK. TetrahedronLett. 1997, 38: 7687 -
10e
Rodriguez AL.Koradin C.Dohle W.Knochel P. Angew. Chem.Int. Ed. 2000, 29: 2488 -
11a
Saulnier MG.Frennesson DB.Deshpande MS.Vyas DM. Tetrahedron Lett. 1995, 36: 7841 -
11b
Ezquerra J.Pedregal C.Lamas C.Barluenga J.Perez M.García-Martín MA.González JM. J. Org. Chem. 1996, 61: 5804 ; and references cited therein -
11c
Ma C.Liu X.Li X.Flippen-Anderson JYS.Cook JM. J.Org. Chem. 2001, 66: 4525 - 13
Sonogashira K.Ohda Y.Hagihara N. TetrahedronLett. 1975, 4467 - 14
Ambros R.von Angerer S.Wiegrebe W. Arch.Pharm. (Weinheim, Ger.) 1988, 321: 743 - 15 For a review, see:
Eliott IW. In The Alkaloids Vol.31:Brossi A. AcademicPress; Orlando: 1987. p.101 -
16a
Kametani T.Ogasawara K. J.Chem. Soc. C 1967, 2208 -
16b
Benington F.Morin RD. J. Org. Chem. 1967, 32: 1050 -
16c
Kametani T.Fukumoto K.Nakano T. J. Heterocycl.Chem. 1972, 9: 1363 -
16d
Kametani T.Shibuya S.Kano S. J.Chem. Soc., Perkin Trans. 1 1973, 1212 -
16e
Ahmad I.Gibson M. Can. J. Chem. 1975, 53: 3660 -
16f
Kessar SV.Batra S.Nadir UK.Gandhi SS. IndianJ. Chem. 1975, 13: 1109 -
16g
Mak C.-P.Brossi A. Heterocycles 1979, 12: 1413 -
16h
Elliot IW. J. Org. Chem. 1982, 47: 5398 -
16i
Boente JM.Castedo L.Rodriguezde Lera A.Saa JM.Suau R.Vidal MC. TetrahedronLett. 1983, 24: 2295 -
16j
Ambros A.von Angerer A.Wiegrebe W. Arch.Pharm. (Weinheim, Ger.) 1988, 321: 481 -
16k
Meyers AI.Sielecki TM. J.Am. Chem. Soc. 1991, 113: 2789 -
16l
Meyers AI.Sielecki TM.Crans DC.Marshman RW.Nguyen TH. J. Am. Chem. Soc. 1992, 57: 3673 -
16m
Cruces J.Estévez JC.Estévez JC.Castedo L. Heterocycles 2000, 53: 1050 -
16n
Orito K.Harada R.Uchito S.Tokuda M. Org. Lett. 2000, 2: 1799 - 17
Ciufolini MA.Qi Hong B.Browne ME. J.Org. Chem. 1988, 53: 4149 - 18
Reboredo FJ.Treus M.Estévez JC.Castedo L.Estévez RJ. Synlett 2002, 999 -
19a
Luo Y.-L.Chou T.-C.Cheng CC. J. Heterocycl. Chem. 1996, 33: 113 -
19b
González E.Pindur U.Schollmeyer D. J. Chem. Soc., Perkin Trans. 1 1996, 1767 ; and references therein - 20
Gribble GW. In TheAlkaloids Vol. 39:Brossi A. AcademicPress, Inc.; New York: 1990. Chap.7. p.239-243
References
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).