Novel Oxidation of Substituted Pyrrolidines by N-Bromosuccinimide - Rapid Synthesis of Pyrrolo[2,1-a]isoquinolines

Abstract

A new method for converting 1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinolines into 5,6-dihydropyrrolo[2,1-a]isoquinolines using N-bromosuccinimide as an oxidant is presented.

azomethine ylides - cycloadditions - oxidation - pyrroles

References and Notes

1a Andersen RJ. Faulkner DJ. Cun-heng H. Van Duyne GD. Clardy J. J. Am. Chem. Soc.  1985,  107:  5492 

1b Cironi P. Albericio F. Alvarez M. In Progress in Heterocyclic Chemistry   Vol. 16:  Gribble GW. Joule JA. Pergamon; Oxford: 2004.  p.1-26  

2a Yamaguchi T. Fukuda T. Ishibashi F. Iwao M. Tetrahedron Lett.  2006,  47:  3755 

2b Fujikawa N. Ohta T. Yamaguchi T. Fukuda T. Ishibashib F. Iwao M. Tetrahedron  2006,  62:  594 

2c Iwao M. Takeuchi T. Fujikawa N. Fukuda T. Ishibashi F. Tetrahedron Lett.  2003,  44:  4443 

3a Díaz M. Guitián E. Castedo L. Synlett  2001,  1164 

3b Zhao B.-X. Yu Y. Eguchi S. Tetrahedron  1996,  52:  12049 

4 Olsen CA. Parera N. Albericio F. Alvarez M. Tetrahedron Lett.  2005,  46:  2041 

5a Ploypradith P. Kagan RK. Ruchirawat S. J. Org. Chem.  2005,  70:  5119 

5b Ploypradith P. Mahidol C. Sahakitpichan P. Wongbundit S. Ruchirawat S. Angew. Chem. Int. Ed.  2004,  43:  866 

5c Kuo R.-Y. Wu C.-C. Chang F.-R. Yeh J.-L. Chen I.-J. Wu Y.-C. Bioorg. Med. Chem. Lett.  2003,  13:  821 

5d Ishibashi F. Tanabe S. Oda T. Iwao M. J. Nat. Prod.  2002,  65:  500 

5e Ruchirawat S. Mutarapat T. Tetrahedron Lett.  2001,  42:  1205 

6 Fujita R. Watanabe N. Tomisawa H. Chem. Pharm. Bull.  2002,  50:  225 

7a La Porta P. Capuzzi L. Bettarini F. Synthesis  1994,  287 

7b DeShong P. Kell DA. Sidler DR. J. Org. Chem.  1985,  50:  2309 

7c Padwa A. Norman BH. J. Org. Chem.  1990,  55:  4801 

7d Cironi P. Cuevas C. Albericioa F. Alvarez M. Tetrahedron  2004,  60:  8669 

7e Cironi P. Manzanares I. Albericio F. Alvarez M. Org. Lett.  2003,  2959 

7f Ridley CPM. Reddy VR. Rocha G. Bushman FD. Faulkner DJ. Bioorg. Med. Chem.  2002,  10:  3285 

7g Banwell M. Flynn B. Hockless D. Chem. Commun.  1997,  2259 

7h Poissonnet G. Theret-Bettiol M.-H. Dodd RH. J. Org. Chem.  1996,  61:  2273 

8a Southwick PL. Sapper DI. Pursglove LA. J. Am. Chem. Soc.  1950,  72:  4940 

8b Cossy J. Pete J.-P. Tetrahedron Lett.  1978,  4941 

8c Cervinka O. Chem. Ind. (London)  1959,  1129 

8d Oussaid B. Garrigues B. Soufiaoui M. Can. J. Chem.  1994,  72:  2483 

8e Bonnaud B. Bigg DCH. Synthesis  1994,  465 

8f Gupta P. Bhaduri AP. Synth. Commun.  1998,  28:  3151 

9a Bende Z. Simon K. Tóth G. Tõke L. Weber L. Liebigs Ann. Chem.  1982,  924 

9b Bende Z. Bitter I. Tõke L. Weber L. Tóth G. Janke F. Liebigs Ann. Chem.  1982,  2146 

9c Bende Z. Tõke L. Weber L. Tóth G. Janke F. Csonka G. Tetrahedron  1983,  40:  369 

9d Tischer T. Tõke L. Tóth G. Acta Chim. Hung.  1990,  127:  171 

9e Fejes I. Nyerges M. Tõke L. Pak CS. Tetrahedron  2000,  56:  639 

9f Fejes I. Nyerges M. Szöllõssy Á. Blaskó G. Tõke L. Tetrahedron  2001,  57:  1129 

9g Nyerges M. Somfai B. Tóth J. Dancsó A. Blaskó G. Tõke L. Synthesis  2005,  2039 

10 Filler R. Chem. Rev.  1963,  63:  21 

11a Ali MH. Hartman M. Lamp K. Schmitz C. Wencewicz T. Synth. Commun.  2006,  36:  1769 

11b Harville R. Rees SF. J. Org. Chem.  1968,  33:  3976 

11c More KM. Wemple J. Synthesis  1977,  791 

11d Surendra K. Krishnaveni NS. Kumar VP. Sridhar R. Rao KR. Tetrahedron Lett.  2005,  46:  4581 

12a Jain SL. Sain B. Synth. Commun.  2006,  36:  1459 

12b Lee JC. Lee JY. Lee JM. Synth. Commun.  2005,  35:  1911 

12c Sharma VB. Jain SL. Sain B. J. Mol. Catal. A: Chem.  2005,  227:  47 

12d Khurana JM. Kandpal BM. Tetrahedron Lett.  2003,  44:  4909 

13 Cheung YF. Tetrahedron Lett.  1979,  40:  3809 

14 Bandgar BP. Makone SS. Synth. Commun.  2006,  36:  1347 

15 Tatsugi J. Zhiwei T. Izawa Y. ARKIVOC  2001,  (i):  67 

16 Suzuki H. Tsutsui H. Kano A. Katoh S. Morita T. Matsuda K. Iibuchi N. Ogawa M. Heterocycles  1997,  45:  1657 

17 Kovganko VN. Kovganko NN. Russ. J. Org. Chem.  2006,  42:  243 

18a Pelletier JC. Cava MP. J. Org. Chem.  1987,  52:  616 

18b Pelletier JC. Cava MP. Synthesis  1987,  474 

19 Stanforth SP. J. Heterocycl. Chem.  1987,  531 

20

General procedure for the preparation of compounds 5a-l: The corresponding cycloadduct (4, 1.0 mmol) was dissolved in CHCl₃ (10 mL) and NBS (0.17 g, 1.1 mmol) was added in one portion. The solution immediately turned yellow. After 30 min stirring H₂O (10 mL) was added and the organic layer was washed with further portions of H₂O (2 × 10 mL) and brine (10 mL), then dried (MgSO₄) and evaporated in vacuo. The residue was triturated with cold EtOH and filtered to yield the title product as a yellow powder. All new compounds afforded correct elemental analyses and spectroscopic data.
Selected examples: Methyl 8,9-dimethoxy-1-nitro-2-phenyl-5,6-dihydropyrrolo[2,1-a]isoquinoline-3-carboxylate (5a): IR (KBr): 2956, 2833, 1700, 1609, 1591, 1561, 1547, 1506, 1452, 1439, 1355, 1284, 1262, 1236, 1217, 1195, 1181, 1136, 1100, 1072, 1016 cm^-1; ¹H NMR (500 MHz, CDCl₃): δ = 7.39 (m, 4 H, Ph-H and H-10), 7.29 (m, 2 H, Ph-H), 6.79 (s, 1 H, H-7), 4.58 (t, J = 6.7 Hz, 2 H, H-5), 3.94 (s, 3 H, OMe), 3.86 (s, 3 H, OMe), 3.53 (s, 3 H, OMe), 3.06 (t, J = 6.7 Hz, 2 H, H-6); ¹³C NMR (125 MHz, CDCl₃): δ = 161.3 (q), 150.2 (q), 147.9 (q), 136.4 (q), 132.3 (q), 130.9 (q), 129.6 (q), 129.5 (2 × CH), 128.1 (q), 127.8 (CH), 127.6 (2 × CH), 117.2 (q), 114.7 (q), 110.5 (CH), 109.9 (CH), 56.5 (CH₃), 56.0 (CH₃), 51.4 (CH₃), 43.0 (CH₂), 28.8 (CH₂).
Methyl 8,9-dimethoxy-2-(2-bromo-3,4,5-trimethoxy-phenyl)-1-nitro-5,6-dihydropyrrolo[2,1-a]isoquinoline-3-carboxylate (5e): IR (KBr): 2993, 2940, 2840, 1709, 1669, 1563, 1505, 1475, 1443, 1427, 1410, 1387, 1361, 1343, 1301, 1287, 1260, 1214, 1195, 1138, 1107, 1049, 1013 cm^-1; ¹H NMR (500 MHz, CDCl₃): δ = 7.49 (s, 1 H, H-10), 6.79 (s, 1 H, H-7), 6.63 (s, 1 H, Ar²-6′H), 4.61 (m, 2 H, H-5), 3.96 (s, 3 H, OMe), 3.95 (s, 3 H, OMe), 3.93 (s, 3 H, OMe), 3.89 (s, 3 H, OMe), 3.83 (s, 3 H, OMe), 3.06 (m, 2 H, H-6); ¹³C NMR (125 MHz, CDCl₃): δ = 160.9 (q), 152.2 (q), 150.7 (q), 150.4 (q), 147.7 (q), 142.5 (q), 131.6 (q), 131.5 (q), 129.7 (q), 128.0 (q), 127.4 (q), 118.6 (q), 117.1 (q), 111.0 (q), 110.5 (CH), 110.4 (CH), 109.8 (CH), 61.2 (CH₃), 61.0 (CH₃), 56.13 (CH₃), 56.12 (CH₃), 56.0 (CH₃), 51.7 (CH₃), 43.0 (CH₂), 28.8 (CH₂).
3-(4-Bromobenzoyl)-2-(2-chlorophenyl)-8,9-dimethoxy-1-nitro-5,6-dihydropyrrolo[2,1-a]isoquinoline (5k): IR (KBr): 3010, 2943, 1633, 1586, 1502, 1471, 1442, 1405, 1355, 1261, 1218, 1148, 1095, 1068, 1056, 1014 cm^-1; ¹H NMR (500 MHz, CDCl₃): δ = 7.54 (s, 1 H, H-10), 7.41 (d, J = 8.4 Hz, 2 H, Ar³-2′ and 6′H), 7.25 (d, J = 8.4 Hz, 2 H, Ar³-3′ and 5′H), 7.19 (d, J = 7.9 Hz, 1 H, Ar²-6′H), 7.07 (t, J = 7.9 Hz, 1 H, Ar²-5′H), 6.97 (d, J = 7.9 Hz, 1 H, Ar²-3′H), 6.95 (d, J = 7.9 Hz, 1 H, Ar²-4′H), 6.81 (s, 1 H, H-7), 4.45 (m, 1 H, H-5), 4.34 (m, 1 H, H-5), 3.96 (s, 3 H, OMe), 3.90 (s, 3 H, OMe), 3.10 (m, 2 H, H-6); ¹³C NMR (125 MHz, CDCl₃): δ = 186.6 (q), 150.6 (q), 147.8 (q), 136.7 (q), 134.3 (q), 133.1 (q), 132.3 (CH), 132.2 (q), 131.0 (q), 130.9 (2 × CH), 130.5 (2 × CH), 129.3 (CH), 129.1 (CH), 128.3 (q), 127.5 (q), 126.7 (q), 126.3 (CH), 125.3 (q), 117.0 (q), 110.6 (CH), 110.5 (CH), 56.2 (CH₃), 56.0 (CH₃), 43.3 (CH₂), 29.0 (CH₂).

21 Fejes I. Nyerges M. Blaskó G. Tőke L. Pak CS. Tetrahedron  2000,  43:  8545 

22 Nyerges M. Tőke L. Tetrahedron Lett.  2005,  46:  7531