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

<A NAME="RD01207ST-1A">1a</A> Andersen RJ. Faulkner DJ. Cun-heng H. Van Duyne GD. Clardy J. J. Am. Chem. Soc.  1985,  107:  5492 

<A NAME="RD01207ST-1B">1b</A> Cironi P. Albericio F. Alvarez M. In Progress in Heterocyclic Chemistry   Vol. 16:  Gribble GW. Joule JA. Pergamon; Oxford: 2004.  p.1-26  

<A NAME="RD01207ST-2A">2a</A> Yamaguchi T. Fukuda T. Ishibashi F. Iwao M. Tetrahedron Lett.  2006,  47:  3755 

<A NAME="RD01207ST-2B">2b</A> Fujikawa N. Ohta T. Yamaguchi T. Fukuda T. Ishibashib F. Iwao M. Tetrahedron  2006,  62:  594 

<A NAME="RD01207ST-2C">2c</A> Iwao M. Takeuchi T. Fujikawa N. Fukuda T. Ishibashi F. Tetrahedron Lett.  2003,  44:  4443 

<A NAME="RD01207ST-3A">3a</A> Díaz M. Guitián E. Castedo L. Synlett  2001,  1164 

<A NAME="RD01207ST-3B">3b</A> Zhao B.-X. Yu Y. Eguchi S. Tetrahedron  1996,  52:  12049 

<A NAME="RD01207ST-4">4</A> Olsen CA. Parera N. Albericio F. Alvarez M. Tetrahedron Lett.  2005,  46:  2041 

<A NAME="RD01207ST-5A">5a</A> Ploypradith P. Kagan RK. Ruchirawat S. J. Org. Chem.  2005,  70:  5119 

<A NAME="RD01207ST-5B">5b</A> Ploypradith P. Mahidol C. Sahakitpichan P. Wongbundit S. Ruchirawat S. Angew. Chem. Int. Ed.  2004,  43:  866 

<A NAME="RD01207ST-5C">5c</A> 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 

<A NAME="RD01207ST-5D">5d</A> Ishibashi F. Tanabe S. Oda T. Iwao M. J. Nat. Prod.  2002,  65:  500 

<A NAME="RD01207ST-5E">5e</A> Ruchirawat S. Mutarapat T. Tetrahedron Lett.  2001,  42:  1205 

<A NAME="RD01207ST-6">6</A> Fujita R. Watanabe N. Tomisawa H. Chem. Pharm. Bull.  2002,  50:  225 

<A NAME="RD01207ST-7A">7a</A> La Porta P. Capuzzi L. Bettarini F. Synthesis  1994,  287 

<A NAME="RD01207ST-7B">7b</A> DeShong P. Kell DA. Sidler DR. J. Org. Chem.  1985,  50:  2309 

<A NAME="RD01207ST-7C">7c</A> Padwa A. Norman BH. J. Org. Chem.  1990,  55:  4801 

<A NAME="RD01207ST-7D">7d</A> Cironi P. Cuevas C. Albericioa F. Alvarez M. Tetrahedron  2004,  60:  8669 

<A NAME="RD01207ST-7E">7e</A> Cironi P. Manzanares I. Albericio F. Alvarez M. Org. Lett.  2003,  2959 

<A NAME="RD01207ST-7F">7f</A> Ridley CPM. Reddy VR. Rocha G. Bushman FD. Faulkner DJ. Bioorg. Med. Chem.  2002,  10:  3285 

<A NAME="RD01207ST-7G">7g</A> Banwell M. Flynn B. Hockless D. Chem. Commun.  1997,  2259 

<A NAME="RD01207ST-7H">7h</A> Poissonnet G. Theret-Bettiol M.-H. Dodd RH. J. Org. Chem.  1996,  61:  2273 

<A NAME="RD01207ST-8A">8a</A> Southwick PL. Sapper DI. Pursglove LA. J. Am. Chem. Soc.  1950,  72:  4940 

<A NAME="RD01207ST-8B">8b</A> Cossy J. Pete J.-P. Tetrahedron Lett.  1978,  4941 

<A NAME="RD01207ST-8C">8c</A> Cervinka O. Chem. Ind. (London)  1959,  1129 

<A NAME="RD01207ST-8D">8d</A> Oussaid B. Garrigues B. Soufiaoui M. Can. J. Chem.  1994,  72:  2483 

<A NAME="RD01207ST-8E">8e</A> Bonnaud B. Bigg DCH. Synthesis  1994,  465 

<A NAME="RD01207ST-8F">8f</A> Gupta P. Bhaduri AP. Synth. Commun.  1998,  28:  3151 

<A NAME="RD01207ST-9A">9a</A> Bende Z. Simon K. Tóth G. Tõke L. Weber L. Liebigs Ann. Chem.  1982,  924 

<A NAME="RD01207ST-9B">9b</A> Bende Z. Bitter I. Tõke L. Weber L. Tóth G. Janke F. Liebigs Ann. Chem.  1982,  2146 

<A NAME="RD01207ST-9C">9c</A> Bende Z. Tõke L. Weber L. Tóth G. Janke F. Csonka G. Tetrahedron  1983,  40:  369 

<A NAME="RD01207ST-9D">9d</A> Tischer T. Tõke L. Tóth G. Acta Chim. Hung.  1990,  127:  171 

<A NAME="RD01207ST-9E">9e</A> Fejes I. Nyerges M. Tõke L. Pak CS. Tetrahedron  2000,  56:  639 

<A NAME="RD01207ST-9F">9f</A> Fejes I. Nyerges M. Szöllõssy Á. Blaskó G. Tõke L. Tetrahedron  2001,  57:  1129 

<A NAME="RD01207ST-9G">9g</A> Nyerges M. Somfai B. Tóth J. Dancsó A. Blaskó G. Tõke L. Synthesis  2005,  2039 

<A NAME="RD01207ST-10">10</A> Filler R. Chem. Rev.  1963,  63:  21 

<A NAME="RD01207ST-11A">11a</A> Ali MH. Hartman M. Lamp K. Schmitz C. Wencewicz T. Synth. Commun.  2006,  36:  1769 

<A NAME="RD01207ST-11B">11b</A> Harville R. Rees SF. J. Org. Chem.  1968,  33:  3976 

<A NAME="RD01207ST-11C">11c</A> More KM. Wemple J. Synthesis  1977,  791 

<A NAME="RD01207ST-11D">11d</A> Surendra K. Krishnaveni NS. Kumar VP. Sridhar R. Rao KR. Tetrahedron Lett.  2005,  46:  4581 

<A NAME="RD01207ST-12A">12a</A> Jain SL. Sain B. Synth. Commun.  2006,  36:  1459 

<A NAME="RD01207ST-12B">12b</A> Lee JC. Lee JY. Lee JM. Synth. Commun.  2005,  35:  1911 

<A NAME="RD01207ST-12C">12c</A> Sharma VB. Jain SL. Sain B. J. Mol. Catal. A: Chem.  2005,  227:  47 

<A NAME="RD01207ST-12D">12d</A> Khurana JM. Kandpal BM. Tetrahedron Lett.  2003,  44:  4909 

<A NAME="RD01207ST-13">13</A> Cheung YF. Tetrahedron Lett.  1979,  40:  3809 

<A NAME="RD01207ST-14">14</A> Bandgar BP. Makone SS. Synth. Commun.  2006,  36:  1347 

<A NAME="RD01207ST-15">15</A> Tatsugi J. Zhiwei T. Izawa Y. ARKIVOC  2001,  (i):  67 

<A NAME="RD01207ST-16">16</A> Suzuki H. Tsutsui H. Kano A. Katoh S. Morita T. Matsuda K. Iibuchi N. Ogawa M. Heterocycles  1997,  45:  1657 

<A NAME="RD01207ST-17">17</A> Kovganko VN. Kovganko NN. Russ. J. Org. Chem.  2006,  42:  243 

<A NAME="RD01207ST-18A">18a</A> Pelletier JC. Cava MP. J. Org. Chem.  1987,  52:  616 

<A NAME="RD01207ST-18B">18b</A> Pelletier JC. Cava MP. Synthesis  1987,  474 

<A NAME="RD01207ST-19">19</A> Stanforth SP. J. Heterocycl. Chem.  1987,  531 

<A NAME="RD01207ST-20">20</A>

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).

<A NAME="RD01207ST-21">21</A> Fejes I. Nyerges M. Blaskó G. Tőke L. Pak CS. Tetrahedron  2000,  43:  8545 

<A NAME="RD01207ST-22">22</A> Nyerges M. Tőke L. Tetrahedron Lett.  2005,  46:  7531