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 2014; 25(07): 955-958
DOI: 10.1055/s-0033-1340861
DOI: 10.1055/s-0033-1340861
letter
A Concise Approach Toward Tetrazolyl-Substituted Benzazocines via a Novel Isocyanide-Based Multicomponent Reaction
Further Information
Publication History
Received: 20 November 2013
Accepted after revision: 04 February 2014
Publication Date:
11 March 2014 (online)
![](https://www.thieme-connect.de/media/synlett/201407/lookinside/thumbnails/10.1055-s-0033-1340861-1.jpg)
Abstract
The synthesis of pharmacologically relevant isoquinoline-tetrazoles and benzazocine-tetrazoles via sequential azido-Ugi and alkyne-induced ring-expansion reactions starting from cotarnine chloride are reported. A one-pot, multicomponent reaction protocol toward the ring-expanded product is also described.
Supporting Information
- for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
- Supporting Information
-
References and Notes
- 1a Li JW.-H, Vederas JC. Science 2009; 325: 161
- 1b Newman DJ, Cragg GM. J. Nat. Prod. 2007; 70: 461
- 1c Ganesan A. Curr. Opin. Chem. Biol. 2008; 12: 306
- 1d McChesney JD. Phytochemistry 2007; 68: 2015
- 1e Shelar DB, Shirote PJ. Biomed. Pharm. J. 2011; 4: 141
- 1f Mishra BB, Tiwari VK. Eur. J. Med. Chem. 2011; 46: 4769
- 2 McArdle BM, Quinn RJ. ChemBioChem 2007; 8: 788
- 3a Shevyakov SV, Davydova OI, Kiselyov AS, Kravchenko DV, Ivachtchenko AV, Krasavin M. Nat. Prod. Res. 2006; 20: 871
- 3b Floss HG. J. Biotechnol. 2006; 124: 242
- 4a Boldi AM. Curr. Opin. Chem. Biol. 2004; 9: 281
- 4b Sandulenko Y, Krasavin M. Chem. Heterocycl. Compd. 2012; 48: 606
- 5a Beke D. Adv. Heterocycl. Chem. 1963; 1: 167
- 5b Krasnov KA, Kartsev VG, Khrustalev VN. Heterocycles 2007; 71: 13
-
5c Ukhin LYu, Suponitskii KYu, Kartsev VG. Chem. Nat. Compd. 2003; 39: 482
- 5d Lamblin M, Couture A, Deniau E, Grandclaudon P. Org. Biomol. Chem. 2007; 5: 1466
- 6a Voskressensky LG, Borisov RS, Kulikova LN, Kleimenov AV, Borisova TN, Varlamov AV. Chem. Heterocycl. Compd. 2012; 48: 680
- 6b Borisov RS, Polyakov AI, Medvedeva LA, Khrustalev VN, Guranova NI, Voskressensky LG. Org. Lett. 2010; 12: 3894
- 7a Voskressensky LG, Borisova TN, Soklakova TA, Kulikova LN, Borisov RS, Varlamov AV. Lett. Org. Chem. 2005; 2: 18
- 7b Voskressensky LG, Borisova TN, Kostenev IS, Vorobiev IV, Varlamov AV. Tetrahedron Lett. 2005; 46: 1975
- 8 Zabrocki J, Smith GD, Dunbar JB. Jr, Iijima H, Marshall GR. J. Am. Chem. Soc. 1988; 110: 5875
- 9 Gunawan S, Hulme C. Org. Biomol. Chem. 2013; 11: 6036
- 10a Ugi I, Steinbruckner C. Chem. Ber. 1961; 94: 734
- 10b Ugi I. Angew. Chem., Int. Ed. Engl. 1962; 1: 8
- 10c Yue T, Wang M.-X, Wang D.-X, Zhu J. Angew. Chem. Int. Ed. 2008; 47: 9454
- 10d Mayer J, Umkehrer M, Kalinski C, Ross G, Kolb J, Burdack C, Hiller W. Tetrahedron Lett. 2005; 46: 7393
- 10e Soeta T, Tamura K, Fujinami S, Ukaji Y. Org. Biomol. Chem. 2013; 11: 2168
- 11 Voskressensky LG, Borisova TN, Listratova AV, Kulikova LN, Titov AA, Varlamov AV. Tetrahedron Lett. 2006; 47: 4585
- 12 Isoquinoline-Tetrazoles 4a–i; General Procedure Cotarnine chloride (2) (1 mmol), isonitrile 3 (1.2 mmol) and NaN3 (1.2 mmol) were dissolved in H2O–MeOH (1:5, 5 mL), and the mixture was stirred at r.t. for 18–24 h (TLC monitoring). Products 4a,b were isolated using flash chromatography (EtOAc–hexanes, from 1:50 to 1:10). Products 4c–i precipitated from the reaction mixtures and were removed by filtration, washed with cold MeOH (15 mL) and dried in air. 5-(1-Cyclohexyl-1H-tetrazol-5-yl)-4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinoline (4а) Yield: 189 mg (51%); colorless powder; mp 147–149 °C (EtOAc–hexanes); reaction time = 19 h.1H NMR (600 MHz, DMSO-d 6): δ = 1.18–1.33 (m, 2 H), 1.37–1.47 (m, 1 H), 1.60–1.71 (m, 2 H), 1.72–1.79 (m, 2 H), 1.79–1.87 (m, 2 H), 1.91–1.97 (m, 1 H), 2.21 (s, 3 H), 2.56 (dt, J = 4.8, 11.7 Hz, 1 H), 2.64 (dt, J = 4.8, 16.5 Hz, 1 H), 2.79–2.86 (m, 1 H), 2.90–2.96 (m, 1 H), 3.50 (s, 3 H), 4.51–4.59 (m, 1 H), 5.18 (s, 1 H), 5.90 (d, J = 9.6 Hz, 2 H), 6.50 (s, 1 H). 13C NMR (150 MHz, DMSO-d 6): δ = 25.1, 25.2, 25.3, 26.8, 33.1, 33.2, 42.2, 46.8, 52.7, 57.1, 59.3, 101.4, 103.3, 118.2, 129.5, 134.5, 139.9, 148.8, 154.6. HRMS (MALDI): m/z [M + Na]+ calcd for C19H25N5O3Na: 394.1849; found: 394.1861. Azocines 5; General Procedure DMAD, methyl propiolate or acetyl acetylene (1.2 mmol) was added to a solution of derivative 4a,c (1 mmol) in TFE (10 mL). The mixture was stirred for 4–8 hours at 35 °C (TLC monitoring). The solvent was evaporated under reduced pressure and the residue was crystallized from EtOAc–hexane to give the corresponding benzazocine-tetrazole 5a–d. Methyl 10-(1-Benzyl-1H-tetrazol-5-yl)-11-methoxy-7-methyl-5,6,7,10-tetrahydro[1,3]dioxolo[4′,5′:4,5]benzo-[1,2-d]azocine-9-carboxylate (5a) Yield: 350 mg (75%), pale brown solid; mp 116–118 °С; reaction time = 8 h. 1H NMR (400 MHz, CDCl3): δ = 2.74 (dt, J = 5.5, 16.5 Hz, 1 H), 2.80 (s, 3 H), 2.80–2.88 (m, 1 H), 2.49 (dt, J = 5.5, 15.1 Hz, 1 H), 3.68 (s, 3 H), 3.78 (s, 3 H), 3.96–4.08 (m, 1 H), 5.42 (AB, J = 15.6 Hz, 2 H), 5.90 (s, 2 H), 6.25 (s, 1 H), 6.86 (s, 1 H), 7.00–7.44 (m, 2 H), 7.21–7.29 (m, 3 H), 7.33 (s, 1 H). 13C NMR (100 MHz, DMSO-d 6): δ = 29.9, 35.2, 45.3, 50.6, 51.6, 52.4, 60.2, 92.9, 101.3, 105.8, 121.8, 127.2 (2 С), 128.1, 128.6 (2 С), 132.9, 134.3, 136.2, 141.3, 148.1, 154.2, 159.3, 169.7. HRMS (MALDI): m/z [M + Na]+ calcd for C24H25N5O5Na: 486.1747; found: 486.1758.
For examples of Ugi-azide reactions, see: