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(01): 41-44
DOI: 10.1055/s-0035-1560815
DOI: 10.1055/s-0035-1560815
letter
Stereoselective Synthesis of Densely Substituted Tetrahydroquinolines by a Conjugate Addition Nitro-Mannich Reaction with Carbon Nucleophiles
Further Information
Publication History
Received: 21 September 2015
Accepted after revision: 14 October 2015
Publication Date:
30 October 2015 (online)
Dedicated to my friend and mentor Professor Steven V. Ley for his guidance and inspiration
Abstract
Conjugate addition of an alkyl group to a series of 2-imino-nitrostyrenes and then addition of trifluoroacetic acid initiates a nitro-Mannich cyclisation to give cis,cis-2,3,4-substituted tetrahydroquinolines in good yield and high diastereoselectivity.
Supporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1560815.
- Supporting Information
-
References and Notes
- 1a Nammalwar B, Bunce RA. Molecules 2014; 19: 204
- 1b Sridharan V, Suryavanshi PA, Menéndez JC. Chem. Rev. 2011; 111: 7157
- 1c Zhou Y.-G. Acc. Chem. Res. 2007; 40: 1357
- 1d Mitchinson A, Nadin A. J. Chem. Soc., Perkin Trans. 1 2000; 2862
- 1e Kouznetsov V, Palma A, Ewert C, Varlamov A. J. Heterocycl. Chem. 1998; 35: 761
- 1f Katrizky AR, Rachwal S, Rachwal B. Tetrahedron 1996; 52: 15031
- 2 Asolkar RN, Schroeder D, Heckmann R, Lang S, Wagner-Doebler I, Laatsch H. J. Antibiot. 2004; 57: 17
- 3 Ransom RW, Graham AC, Bernard AM, Salvatore MJ, Lumma WC, Anderson PS, Pitzenberger SM, Varga SL. J. Am. Chem. Soc. 1995; 117: 6682
- 4a Ueda M, Kawai S, Hayashi M, Naito T, Miyata O. J. Org. Chem. 2010; 75: 914
- 4b Tan HR, Ng HF, Chang J, Wang J. Chem. Eur. J. 2012; 18: 3865
- 4c Jia Z.-X, Luo Y.-C, Wang Y, Chen L, Xu P.-F, Wang B. Chem. Eur. J. 2012; 18: 12958
- 4d Wang K.-T, Kim S.-G. Synthesis 2014; 46: 3365
- 5a Youn SW, Song J.-H, Jung D.-I. J. Org. Chem. 2008; 73: 5658
- 5b Davies SG, Mujtaba N, Roberts PM, Smith AD, Thomson JE. Org. Lett. 2009; 11: 1959
- 5c Kang YK, Kim SM, Kim DY. J. Am. Chem. Soc. 2010; 132: 11847
- 5d Suh CW, Kim DY. Org. Lett. 2014; 16: 5374
- 5e Cao W, Liu X, Guo J, Liu L, Feng X. Chem. Eur. J. 2015; 21: 1632
- 6 Noble A, Anderson JC. Chem. Rev. 2013; 113: 2887
- 7 Anderson JC, Noble A, Ribelles Torres P. Tetrahedron Lett. 2012; 53: 5707
- 8 Maity R, Pan SC. Org. Biomol. Chem. 2015; 13: 6825
- 9 Jia Z.-X, Luo Y.-C, Xu P.-F. Org. Lett. 2011; 13: 832
- 10a Anderson JC, Stepney GJ, Mills MR, Horsfall LR, Blake AJ, Lewis W. J. Org. Chem. 2011; 76: 1961
- 10b Anderson JC, Blake AJ, Koovits PJ, Stepney GJ. J. Org. Chem. 2012; 77: 4711
- 10c Anderson JC, Horsfall LR, Kalogirou AS, Mills MR, Stepney GJ, Tizzard GJ. J. Org. Chem. 2012; 77: 6186
- 10d Anderson JC, Noble A, Tocher DA. J. Org. Chem. 2012; 77: 6703
- 10e Anderson JC, Koovits PJ. Chem. Sci. 2013; 4: 2897
- 10f Anderson JC, Kalogirou AS. Tizzard G. J. Tetrahedron 2014; 17: 9337
- 10g Anderson JC, Campbell IB, Campos S, Shannon J, Tocher DA. Org. Biomol. Chem. 2015; 13: 170
- 11 Anderson JC, Barham JP, Rundell CD. Org. Lett. 2015; 17: 4090
- 12 Alexakis A, Vastra J, Mangeney P. Tetrahedron Lett. 1997; 38: 7745
- 13 The crude 1H NMR also showed >95:5 diastereoselectivity.
- 14 A solution of 5 (0.25 mmol) and Cu(OTf)2 (5 mol%) in Et2O (2.5 mL) was cooled to –78 °C over 30 min. A solution of ZnEt2 (0.375 mL of a 1.0 M solution in hexanes, 1.5 equiv) was added and the mixture stirred for up to 1 h and then stirred for up to 2 h at r.t. The resulting suspension was recooled to –78 °C over 30 min, and TFA (2.5 equiv) was added dropwise, stirred for up to 1 h and then stirred for up to 1 h at r.t. The reaction was then quenched with sat. aq NaHCO3 (50 mL), extracted with EtOAc or CH2Cl2 (3 × 30 mL), the combined organic layers washed with brine (100 mL), dried (Na2SO4), and concentrated in vacuo to give the crude tetrahydroquinoline 6. Purification by column chromatography gave the pure tetrahydroquinoline 6. Analytical Data for 6a Yield 44 mg, 62%; Rf = 0.33 (1:1 CH2Cl2–hexanes). IR (neat): νmax = 3416 (NH), 1545 (NO), 1368 (NO) cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.32–7.45 (m, 5 H, ArH), 7.08–7.16 (m, 2 H, ArH), 6.82 (t, J = 7.5 Hz, 1 H, ArH), 6.68 (dd, J = 7.9, 1.3 Hz, 1 H, ArH), 4.98 (app. t, J = 2.9 Hz, 1 H, CHNO2), 4.76 (d, J = 3.3 Hz, 1 H, CHPh), 4.25 (s, 1 H, NH), 3.20 (ddd, J = 8.3, 5.3, 2.4 Hz, 1 H, CHEt), 1.69–2.01 (m, 2 H, CH 2CH3), 1.12 (t, J = 7.4 Hz, 3 H, CH2CH 3). 13C NMR (151 MHz, CDCl3): δ = 142.5 (ArC), 138.1 (ArC), 129.4 (ArCH), 129.1 (ArCH), 129.1 (ArC), 127.6 (ArCH), 126.8 (ArCH), 121.2 (ArCH), 118.8 (ArCH), 114.7 (ArCH), 86.8 (CH), 54.6 (CH), 41.8 (CHEt), 30.7 (CH2CH3), 11.6 (CH2 CH3). ESI-MS: m/z (%) = 234 (100) [M – H3NO2 +], 45) [M + H+]. HRMS: m/z calcd for C17H19N2O2: 283.1447; found: 283.1448.
- 15 Adams H, Anderson JC, Peace S, Pennell AM. K. J. Org. Chem. 1998; 63: 9932
- 16 Use of AlMe3 gave no reaction.
- 17 Ono N. The Nitro Group in Organic Synthesis . Wiley-VCH; New York: 2001
- 18 Choi H, Hua Z, Ojima I. Org. Lett. 2004; 6: 2689
For reviews, see:
For examples, see:
For examples, see: