Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml
Synlett 2016; 27(18): 2601-2605
DOI: 10.1055/s-0035-1562523
DOI: 10.1055/s-0035-1562523
letter
A One-Pot Synthesis of Highly Functionalized Indolizines by 1,3-Dipolar Cycloaddition of Azomethine Ylides and Phosphorylated Hydroxyketenimines
Further Information
Publication History
Received: 19 May 2016
Accepted after revision: 06 July 2016
Publication Date:
01 August 2016 (online)
![](https://www.thieme-connect.de/media/synlett/201618/lookinside/thumbnails/st-2016-d0348-l_10-1055_s-0035-1562523-1.jpg)
Abstract
Alkyl 2-(alkylamino)-3-(quinolin-2-yl)indolizine-1-carboxylates were prepared by1,3-dipolar cycloaddition of azomethine ylides with phosphorylated hydroxyketenimines, generated in situ by a Nef isocyanide–Perkow cascade.
Key words
Nef reaction - Perkow reaction - cascade reaction - indolizines - dipolar cycloaddition - azomethine ylidesSupporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1562523.
- Supporting Information
-
References and Notes
- 1a Dömling A. Chem. Rev. 2006; 106: 17
- 1b Váradi A, Palmer CT, Dardashti RN, Majumdar S. Molecules 2016; 21: 19
- 1c Rotstein BH, Zaretsky S, Rai V, Yudin AK. Chem. Rev. 2014; 114: 8323
- 2 La Spisa F, Tron GC, El Kaïm L. Synthesis 2014; 46: 829
- 3 Coffinier D, El Kaïm L, Grimaud L. Org. Lett. 2009; 11: 1825
- 4a Komai H, Yoshino T, Matsunaga S, Kanai M. Org. Lett. 2011; 13: 1706
- 4b Yaragorla S, Dada R, Singh G. Synlett 2016; 27: 912
- 5a Dyker G. Angew. Chem. Int. Ed. 1999; 38: 1698
-
5b Colby DA, Bergman RG, Ellman JA. Chem. Rev. 2010; 110: 624
-
5c Ritleng V, Sirlin C, Pfeffer M. Chem. Rev. 2002; 102: 1731
- 5d Zhang G, Luo Y, Wang Y, Zhang L. Angew. Chem. Int. Ed. 2011; 50: 4450
- 6a Lamani M, Prabhu KR. J. Org. Chem. 2011; 76: 7938
- 6b Yanagisawa S, Ueda K, Taniguchi T, Itami K. Org. Lett. 2008; 10: 4673
- 6c Bajracharya GB, Daugulis O. Org. Lett. 2008; 10: 4625
- 6d Sun C.-L, Li H, Yu D.-G, Yu M, Zhou X, Lu X.-Y, Huang K, Zheng S.-F, Li B.-J, Shi Z.-J. Nat. Chem. 2010; 2: 1044
- 6e Chudasama V, Fitzmaurice RJ, Caddick S. Nat. Chem. 2010; 2: 592
- 6f Shirakawa E, Itoh K, Higashino T, Hayashi T. J. Am. Chem. Soc. 2010; 132: 15537
- 6g Liu W, Cao H, Zhang H, Zhang H, Chung KH, He C, Wang H, Kwong FY. Lei A. 2010; 132: 16737
- 7 Kumar A, Gupta G, Srivastava S. Org. Lett. 2011; 13: 6366
- 8 Yavari I, Hosseinpour R, Skoulika S. Synlett 2015; 26: 380
- 9 Yavari I, Hosseinpour R, Pashazadeh R, Ghanbari E, Skoulika S. Tetrahedron 2013; 69: 2462
- 10 Quinolinylindolizines 5; General Procedure A mixture of 2-methylquinoline (0.286 g, 2 mmol) with pyridine or isoquinoline (4 mmol) and I2 (0.506 g, 2 mmol) in MeCN (4 mL) was warmed to 60 °C for 2 h. (i-Pr)2NEt (0.541 g, 4.2 mmol) and a solution of the appropriate ketenimine 1 (2 mmol) in MeCN (1 mL) were added, and the mixture was kept overnight at 60 °C then placed in a freezer for 24 h. The precipitate was collected by filtration and crystallized [hexane–EtOAc (1:5)]. Ethyl 2-(Cyclohexylamino)-3-quinolin-2-ylindolizine-1-carboxylate (5b) Yellow crystals; yield: 0.52 g (68%); mp 227–229 °C. IR (KBr): 3436, 3105, 2928, 2850, 1696, 1600, 1547, 1502, 1448, 1265, 1194 cm–1. 1H NMR (500 MHz, CDCl3): δ = 0.97–1.02 (m, 2 H), 1.11–1.26 (m, 3 H), 1.39–1.42 (m, 1 H), 1.48 (t, J = 7.1 Hz, 3 H), 1.58–1.61 (m, 2 H), 1.86–1.89 (m, 2 H), 2.97–2.03 (m, 1 H), 4.44 (q, J = 7.1 Hz, 2 H), 6.10 (br s, 1 H), 6.78 (t, J = 6.9 Hz, 1 H), 7.17 (t, J = 7.8 Hz, 1 H), 7.51 (t, J = 7.1 Hz, 1 H), 7.72 (t, J = 7.1 Hz, 1 H), 7.80 (d, J = 7.8 Hz, 1 H), 8.08–8.13 (m, 4 H), 9.93 (d, J = 7.0 Hz, 1 H). 13C NMR (125.7 MHz, CDCl3): δ = 14.6 (Me), 24.7 (2 CH2), 25.7 (CH2), 33.7 (2 CH2), 57.1 (CH2O), 59.4 (CH), 94.9 (C), 111.1 (CH), 112.5 (C), 118.0 (C), 122.0 (CH), 124.2 (CH), 124.4 (CH), 125.3 (CH), 125.7 (C), 127.4 (CH), 128.6 (CH), 129.5 (CH), 135.3 (C), 136.1 (CH), 144.8 (CH), 147.3 (C), 152.3 (C), 166.3 (C=O). MS (EI): m/z (%) = 413 (100) [M+], 330 (46), 315 (53), 285 (34), 242 (30), 128 (50), 98 (40), 83 (35), 73 (55). Anal. Calcd for C26H27N3O2 (413.51): C, 75.52; H, 6.58; N, 10.16. Found: C, 75.98; H, 6.64; N, 10.22. X-ray Crystal-Structure Determination of 5b Yellow crystals of compound 5b suitable for single-crystal X-ray diffraction measurements (crystal dimensions: 0.18 × 0.12 × 0.09 mm) were grown by slow evaporation of a solution in EtOH–EtOAc. The unit cell dimensions were determined from 658 reflections. The structure was solved by direct methods and refined by full matrix least-squares calculations based on F2 to a final R1 = 0.0404 and wR2 (all data) = 0.0805, by using SHELXL-2014 and WinGX-2013.3 programs.12 Compound 5b crystallized in the monoclinic system with space group P21/n. A single molecule with molecular formula of C26H27N3O2 was found in the asymmetric unit, giving a total Z = 4 for the unit cell; a = 11.911(2), b = 10.311(2), c = 18.106(4), β = 90.68(3), cell volume V = 2223.5(8)Å3; measurement temperature 293(2) K, measurement range: 2.036 < θ < 24.713; 3767 independent reflections and maximum/minimum residual electron density [e Å3]: 0.136 /–0.13. All nonhydrogen atoms were refined with anisotropic displacement parameters. Hydrogen atoms were placed in ideal positions and refined as riding atoms with relative isotropic displacement parameters. An ORTEP view of the structure is shown in Figure 1. CCDC 1457966 contains the supplementary crystallographic data for compound 5b in this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
- 11 Methyl 2-(Cyclohexylamino)-3-quinolin-2-ylpyrrolo[2,1-a]isoquinoline-1-carboxylate (11a) Yellow crystals; yield: 0.61 g (80%); mp 231–233 °C. IR (KBr): 3347, 3110, 2928, 2850, 1689, 1599, 1546, 1502, 1448, 1265, 1194 cm–1. 1H NMR (500 MHz, CDCl3): δ = 0.94–1.01 (m, 2 H), 1.11–1.17 (m, 3 H), 1.39–1.42 (m, 1 H), 1.56–1.59 (m, 2 H), 1.86–1.88 (m, 2 H), 2.79–2.81 (m, 1 H), 4.04 (s, 3 H), 5.46 (br s, 1 H), 6.99 (d, J = 7.5 Hz, 1 H), 7.45 (t, J = 7.9 Hz, 1 H), 7.50 (d, J = 6.8 Hz, 1 H), 7.51 (t, J = 8.5 Hz, 1 H), 7.62 (d, J = 7.9 Hz, 1 H), 7.72 (t, J = 7.9 Hz, 1 H), 7.79 (d, J = 7.9 Hz, 1 H), 8.13 (d, J = 6.8 Hz, 1 H), 8.14 (t, J = 8.5 Hz, 1 H), 8.27 (d, J = 8.6 Hz, 1 H), 8.94 (d, J = 8.6 Hz, 1 H), 9.54 (d, J = 7.5 Hz, 1 H). 13C NMR (125.7 MHz, CDCl3): δ = 25.1 (2 CH2), 25.7 (CH), 33.8 (2 CH2), 51.4 (MeO), 57.9 (CH), 101.8 (C), 112.8 (CH), 113.8 (C), 122.5 (C), 123.1 (CH), 123.2 (CH), 124.8 (C), 126.0 (CH), 126.3 (CH), 126.4 (CH), 126.6 (CH), 126.8 (CH), 127.1 (CH), 127.5 (C), 129.5 (CH), 129.9 (CH), 131.3 (C), 135.6 (CH), 141.7 (C), 147.5 (C), 152.1 (C), 166.9 (C=O). MS (EI): m/z (%) = 449 (100) [M]+, 416 (42), 374 (50), 346 (30), 308 (55), 279 (30), 240 (32), 208 (30), 167 (20), 128 (50), 83 (40), 55 (45). Anal. Calcd for C29H27N3O2 (449.54): C, 77.48; H, 6.05; N, 9.35. Found: C, 78.02; H, 6.11; N, 9.42.
- 12a Farrugia LJ. J. Appl. Crystallogr. 1999; 32: 837
- 12b Allen FH, Johnson O, Shields GP, Smith BR, Towler M. J. Appl. Crystallogr. 2004; 37: 335
- 12c Macrae CF, Edgington PR, McCabe P, Pidcock E, Shields GP, Taylor R, Towler M, van der Streek J. J. Appl. Crystallogr. 2006; 39: 453
- 12d Burnett MN, Johnson CK. ORTEP-III: Oak Ridge Thermal Ellipsoid Plot Program for Crystal Structure Illustrations, Oak Ridge National Laboratory Report ORNL-6895. Oak Ridge National Laboratory; Oak Ridge: 1996
- 12e Spek AL. J. Appl. Crystallogr. 2003; 36: 7
- 12f Sheldrick GM. Acta Crystallogr., Sect. A 2008; 64: 112
- 12g Coppens P, Leiserowitz L, Rabinovich D. Acta Crystallogr. 1965; 18: 1035
For reviews, see:
For details, see: