A Short and Efficient Approach to Pyrrolo[2,1-a]isoquinoline and Pyrrolo[2,1-a]benzazepine Derivatives

Abstract

A Brønsted acid promoted intramolecular Friedel–Crafts cyclization of β-benzoyl- and β-acetylpyrrol-2(5H)-one derivatives tethered via nitrogen to an electron-rich arene nucleus is developed. Using this efficient methodology, various pyrrolo[2,1-a]isoquinoline and pyrrolo[2,1-a]benzazepine derivatives are prepared in a two-step sequence starting from readily available ethyl (Z)-3-bromomethyl-4-oxo-4-phenylbut-2-enoate or ethyl (Z)-3-bromomethyl-4-oxopent-2-enoate.

Key words

Friedel–Crafts reaction - nitrogen heterocycles - alkaloids - lactams - Brønsted acids

• References

• 1 For a review of the chemistry of pyrrolo[2,1-a]isoquinolines, see: Mikhailovskii AG, Shklyaev VS. Chem. Heterocycl. Compd. 1997; 33: 243
• 2a King FD, Aliev AE, Caddick S, Copley RC. B. Org. Biomol. Chem. 2009; 7: 3561
• 2b King FD, Aliev AE, Caddick S, Tocher DA. Org. Biomol. Chem. 2011; 9: 1547; and cited literature
• 3 For a recent synthesis, see: Kawai N, Matsuda M, Uenishi J. Tetrahedron 2011; 67: 8648
• 4 Moreno L, Párraga J, Galán A, Cabedo N, Primo J, Cortes D. Bioorg. Med. Chem. 2012; 20: 6589 ; and cited literature
• 5 Liu D, Shen T, Xiang L. Helv. Chim. Acta 2001; 94: 497
• 6 Li Q, Jiang J, Fan A, Cui Y, Jia X. Org. Lett. 2011; 13: 312 ; and cited literature
• 7a Khiati S, Seol Y, Agama K, Rosa ID, Agrawal S, Fesen K, Zhang H, Neuman KC, Pommier Y. Mol. Pharm. 2014; 86: 193
• 7b Shen L, Xie N, Yang B, Hu Y, Zhang Y. Eur. J. Med. Chem. 2014; 85: 807
• 8a Pérard-Viret J, Souquet F, Manisse M.-L, Royer J. Tetrahedron Lett. 2010; 51: 96
• 8b Zubkov FI, Ershova JD, Zaytsev VP, Obushak MD, Matiychuk VS, Sokolova EA, Khrustalev VN, Varlamov AV. Tetrahedron Lett. 2010; 51: 6822
• 9a Tietze LF, Tolle N, Kratzert D, Stalke D. Org. Lett. 2009; 11: 5230
• 9b Paladino M, Zaifman J, Ciufolini MA. Org. Lett. 2015; 17: 3422 ; and cited literature
• 10 Suyavaran A, Ramamurthy C, Mareeswaran R, Shanthi YV, Selvakumar J, Mangalaraj S, Kumar MS, Ramanathan CR, Thirunavukkarasu C. Bioorg. Med. Chem. 2015; 23: 488

For selected syntheses of these frameworks, see:
• 11a Ishihara Y, Kiyota Y, Goto G. Chem. Pharm. Bull. 1990; 38: 3024
• 11b Katritzky AR, Maimait R, Xu Y.-J, Akhmedova RG. Synthesis 2002; 601
• 11c Moreau A, Couture A, Deniau E, Grandclaudon P, Lebrun S. Tetrahedron 2004; 60: 6169
• 11d Chowdappa N, Sherigara BS, Augustine JK, Areppa K, Mandal AB. Synthesis 2010; 2949
• 11e Gurram M, Gyimóthy B, Wang R, Lam SQ, Ahmed F, Herr RJ. J. Org. Chem. 2011; 76: 1605
• 11f Louafi F, Moreau J, Shahane S, Golhen S, Roisnel T, Sinbandhit S, Hurvois J.-P. J. Org. Chem. 2011; 76: 9720
• 11g Iza A, Ugarriza I, Uria U, Reyes E, Carrillo L, Vicario JL. Tetrahedron 2013; 69: 8878
• 11h Min J.-Y, Kim G. J. Org. Chem. 2014; 79: 1444
• 11i Islas-Jácome A, Gutiérrez-Carrillo A, García-Garibay MA, González-Zamora E. Synlett 2014; 25: 403

For selected reviews, see:
• 12a Speckamp WN, Hiemstra H. Tetrahedron 1985; 41: 4367
• 12b Speckamp WN, Moolenaar MJ. Tetrahedron 2000; 56: 3817 ; and cited literature

For selected reviews of reactions involving N-acyliminium ions, see:
• 13a Maryanoff BE, Zhang H.-C, Cohen JH, Turchi IJ, Maryanoff CA. Chem. Rev. 2004; 104: 1431
• 13b Yazici A, Pyne SG. Synthesis 2009; 339
• 13c Yazici A, Pyne SG. Synthesis 2009; 513
• 13d Martinez-Estibalez U, Gomez-SanJuan A, Garcia-Calvo O, Aranzamendi E, Lete E, Sotomayor N. Eur. J. Org. Chem. 2011; 3610 ; and cited literature

For selected examples of Brønsted acid promoted cyclization of N-acyliminium ions on π-nucleophilic aromatic rings, see:
• 14a Tanis SP, Deaton MV, Dixon LA, McMills MC, Raggon JW, Collins MA. J. Org. Chem. 1998; 63: 6914
• 14b Kałuża Z, Mostowicz D. Tetrahedron: Asymmetry 2003; 14: 225
• 14c Rose MD, Cassidy MP, Rashatasakhon P, Padwa A. J. Org. Chem. 2007; 72: 538
• 14d Allin SM, Gaskell SN, Towler JM. R, Page PC. B, Saha B, McKenzie MJ, Martin WP. J. Org. Chem. 2007; 72: 8972
• 14e Grigg R, Sridharan V, Sykes DA. Tetrahedron 2008; 64: 8952
• 14f Shengule SR, Ryder G, Willis AC, Pyne SG. Tetrahedron 2012; 68: 10280
• 14g Stepakov AV, Ledovskaya MS, Boitsov VM, Molchanov AP, Kostikov RR, Gurzhiy VV, Starova GL. Tetrahedron Lett. 2012; 53: 5414
• 14h Goff DA. Tetrahedron 2013; 69: 242
• 14i Ledovskaya MS, Molchanov AP, Boitsov VM, Kostikov RR, Stepakov AV. Tetrahedron 2015; 71: 1952

For selected examples of Brønsted acid promoted cyclization of imide carbonyl groups on π-nucleophilic aromatic rings, see:
• 15a Selvakumar J, Ramanathan CR. Org. Biomol. Chem. 2011; 9: 7643
• 15b Selvakumar J, Rao RS, Srinivasapriyan V, Marutheeswaran S, Ramanathan CR. Eur. J. Org. Chem. 2015; 2175
• 16 Ben Othman R, Affani R, Tranchant M.-J, Antoniotti S, Dalla V, Duñach E. Angew. Chem. Int. Ed. 2010; 49: 776
• 17 For an example of Brønsted acid promoted intramolecular Friedel–Crafts-type Michael addition of a δ-tethered π-nucleophilic aromatic ring α,β-unsaturated δ-lactam, see: Fang B, Zheng H, Zhao C, Jing P, Li H, Xie X, She X. J. Org. Chem. 2012; 77: 8367
• 18 For an example of Brønsted acid promoted intramolecular Friedel–Crafts-type Michael addition of δ-tethered π-nucleophilic aromatic ring α,β-unsaturated δ-lactones, see: Sun Y, Yu B, Wang X, Tang S, She X, Pan X. J. Org. Chem. 2010; 75: 4224
• 19 Jebali K, Arfaoui A, Saadi F, Lebreton J, Amri H. Synth. Commun. 2014; 44: 3400
• 20 Hamon M, Dickinson N, Devineau A, Bolien D, Tranchant M.-J, Taillier C, Jabin I, Harrowven DC, Whitby RJ, Ganesan A, Dalla V. J. Org. Chem. 2014; 79: 1900
• 21 See ref. 20 for a discussion of the mechanism and also: Ascic E, Jensen JF, Nielsen TE. Angew. Chem. Int. Ed. 2011; 50: 5188
• 22 The structure of racemic compound 6h was established by single X-ray diffraction analysis. The ORTEP diagram of compound 6h is shown in the Supporting Information.
• 23 Langlois M, Bremont B, Shen S, Poncet A, Andrieux J, Sicsic S, Serraz I, Mathe-Allainmat M, Renard P, Delagrange P. J. Med. Chem. 1995; 38: 2050