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Synlett 2013; 24(17): 2279-2281
DOI: 10.1055/s-0033-1339757
DOI: 10.1055/s-0033-1339757
letter
A Novel Synthesis of Tetrasubstituted Pyrroles via Tandem Benzylic Oxidative Cyclization
Further Information
Publication History
Received: 17 July 2013
Accepted after revision: 18 August 2013
Publication Date:
13 September 2013 (online)

Abstract
A new method for the synthesis of tetrasubstituted pyrroles from a domino reaction between primary benzylamines and dialkyl acetylenedicarboxylates, in the presence of potassium cyanide without using a metal or oxidant, is described.
Supporting Information
- for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
- Supporting Information
-
References and Notes
- 1 Tietze LF, Brasche G, Gericke KM. Domino Reactions in Organic Synthesis . Wiley-VCH; Weinheim: 2006
- 2 Multicomponent Reactions . Zhu J, Bienayme H. Wiley-VCH; Weinheim: 2005
- 3 Colby DA, Bergman RG, Ellman JA. Chem. Rev. 2010; 110: 624
- 4 Yeung CS, Dong VM. Chem. Rev. 2011; 111: 1215
- 5 Chen X, Engle KM, Wang DH, Yu JQ. Angew. Chem. Int. Ed. 2009; 48: 5094
- 6 Young IS, Thornton PD, Thompson A. Nat. Prod. Rep. 2010; 27: 1801
- 7 Estevez V, Villacampa M, Menendez JC. Chem. Soc. Rev. 2010; 39: 4402
- 8 Thirumalairajan S, Pearce BM, Thompson A. Chem. Commun. 2010; 46: 1797
- 9 Fan H, Peng J, Hamann MT, Hu JF. Chem. Rev. 2008; 108: 264
- 10 Loudet A, Burgess K. Chem. Rev. 2007; 107: 4891
- 11 Wood TE, Thompson A. Chem. Rev. 2007; 107: 1831
- 12 Khlebnikov AF, Golovkina MV, Novikov MS, Yufit DS. Org. Lett. 2012; 14: 3768
- 13 Das B, Reddy GC, Balasubramanyan P, Veeranjaneyulu B. Synthesis 2010; 1625
- 14 Liu W, Jiang H, Huang L. Org. Lett. 2010; 12: 312
- 15 Morin MS. T, Arndtsen BA. Org. Lett. 2010; 12: 4916
- 16 Herath A, Cosford ND. P. Org. Lett. 2010; 12: 5182
- 17 Ciez D. Org. Lett. 2009; 11: 4282
- 18 Hong D, Zhu Y, Li Y, Lin X, Lu P, Wang Y. Org. Lett. 2011; 13: 4668
- 19 Hikawa H, Ino Y, Suzuki H, Yokoyama Y. J. Org. Chem. 2012; 77: 7046
- 20 Wendlandt AE, Stahl SS. Org. Lett. 2012; 14: 2850
- 21 Gao QH, Fei Z, Zhu YP, Lian M, Jia FC, Liu MC, She NF, Wu AX. Tetrahedron 2013; 69: 22
- 22 Karnakar K, Kumar AV, Murthy SN, Ramesh K, Nageswar YV. D. Tetrahedron Lett. 2012; 53: 4613
- 23 Liu P, Li Y, Wang H, Wang Z, Hu X. Tetrahedron Lett. 2012; 53: 6654
- 24 Rachkonda S, Pratap PS, Basaveswara Rao MV. Synthesis 2012; 44: 2065
- 25 Moriyama K, Takemura M, Togo H. Org. Lett. 2012; 14: 2414
- 26 Patil RD, Adimurthy S. Adv. Synth. Catal. 2011; 353: 1695
- 27 Xu W, Jin Y, Liu H, Jiang Y, Fu H. Org. Lett. 2011; 13: 1274
- 28 Chen Z, Zhu J, Xie H, Li S, Wu Y, Gong Y. Org. Lett. 2010; 12: 4376
- 29 Yavari I, Souri S, Sirouspour M. Synlett 2008; 1633
- 30 Yavari I, Souri S. Synlett 2007; 2969
- 31 Yavari I, Nematpour M. Synlett 2013; 24: 165
- 32 Yavari I, Nematpour M. Synlett 2012; 23: 2215
- 33 Yavari I, Bayat MJ. Tetrahedron Lett. 2011; 52: 6649
- 34 General Procedure for the Synthesis of Compounds 3 To a stirred solution of amine 1 (1 mmol) and acetylenic ester 2 (2 mmol) in MeCN (5 mL) was added KCN (1 mmol) at r.t. After completion of the reaction [about 24 h; TLC (EtOAc–hexane, 1:5) monitoring], the solvent was evaporated, and the residue was purified by column chromatography [silica gel (230–400 mesh; Merck); EtOAc–hexane, 1:5] to give pure product. Trimethyl 5-Phenyl-1H-pyrrole-2,3,4-tricarboxylate (3a) Pale yellow oil; yield 0.19 g (61%). IR (KBr): 3421, 3000, 1728, 1610 cm–1. 1H NMR (500.1 MHz, CDCl3): δ = 3.76, 3.79, 4.04 (9 H, s, 3 MeO), 7.45–7.47 (3 H, m, CH), 7.06 (2 H, d, 3 J = 7.8 Hz, CH), 9.24 (1 H, br s, NH) ppm. 13C NMR (125.7 MHz, CDCl3): δ = 51.5, 52.3, 52.7 (3 MeO), 122.4 (C), 126.3 (C), 128.3 (2 CH), 128.6 (C), 129.9 (2 CH), 129.6 (CH), 131.9 (C), 142.6 (C), 161.7 (C=O), 164.9 (C=O), 167.8 (C=O) ppm. MS (EI): m/z (%) = 317 (3) [M+], 302 (4), 258 (23), 91 (14), 77 (6), 59 (7). Anal. Calcd for C16H15NO6 (317.29): C, 60.57; H, 4.56; N, 4.41. Found: C, 60. 75; H, 4.52; N, 4.47. General Procedure for the Synthesis of Compounds 5 To a stirred solution of 4-methylbenzylamine (1b, 1 mmol), DMAD (1 mmol), and methyl propiolate (4a, 1 mmol) in MeCN (5 mL) was added KCN (1 mmol) at r.t. After completion of the reaction [about 24 h; TLC (EtOAc–hexane, 1:5) monitoring], the solvent was evaporated, and the residue was purified by column chromatography [silica gel (230–400 mesh; Merck); EtOAc–hexane, 1:5] to give pure product. Dimethyl 2-{[(E)-3-Methoxy-3-oxoprop-1-enyl](4-methylbenzyl)amino}maleate (5a) Pale yellow powder; mp 94–96 °C; yield 0.22 g (63%). IR (KBr): 3415, 2952, 1712, 1590 cm–1. 1H NMR (500.1 MHz, CDCl3): δ = 2.36 (3 H, s, Me), 3.62, 3.67, 4.02 (9 H, s, MeO), 4.83 (2 H, s, CH2N), 5.17 (1 H, d, 3 J = 13.3 Hz, CH), 5.24 (1 H, s, CH), 7.03 (2 H, d, 3 J = 7.8 Hz, CH), 7.16 (2 H, t, 3 J = 7.8 Hz, CH), 7.59 (2 H, t, 3 J = 13.3 Hz, CH) ppm. 13C NMR (125.7 MHz, CDCl3): δ = 21.0 (Me), 51.1 (CH2N), 51.5, 51.6, 53.4 (3 MeO), 97.1 (CH), 98.8 (CH), 125.7 (2 CH), 129.8 (2 CH), 130.0 (C), 137.7 (C), 143.4 (CH), 150.1 (C), 164.4 (C=O), 166.2 (C=O), 167.5 (C=O) ppm. MS (EI): m/z (%) = 347 (3) [M+], 332 (8), 288 (11), 105 (25), 77 (13), 59 (7). Anal. Calcd for C18H21NO6 (347.36): C, 62.24; H, 6.09; N, 4.03. Found: C, 62.51; H, 6.14; N, 4.08.
- 35 Schmidt G, Winterfeldt E. Chem. Ber. 1971; 104: 2483