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Synlett 2013; 24(1): 49-52
DOI: 10.1055/s-0032-1317667
DOI: 10.1055/s-0032-1317667
letter
Double Palladium-Catalyzed Synthesis of Azepines
Further Information
Publication History
Received: 04 October 2012
Accepted after revision: 26 October 2012
Publication Date:
27 November 2012 (online)
Abstract
The synthesis of new 5H-pyridobenzazepine and 5H-dipyridoazepine compounds using as key step a palladium-catalyzed amination–cyclization reaction is reported. By choosing an appropriate combination of ligands and reactants under standardized reaction conditions, N- and S-tricyclic products can be prepared in one step from the appropriate stilbenes.
Supporting Information
- for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
Included are detailed experimental procedures and spectra for all isolated compounds.
- Supporting Information
-
References and Notes
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- 23 General Procedure for Pd-Catalyzed Synthesis of Azepines A reaction tube containing a stirrer bar was evacuated and backfilled with argon. The tube was then charged with Pd(OAc)2 (5 mol%), JohnPhos (10 mol%), and NaOt-Bu (2.8 equiv) under argon. Toluene was added. After stirring at r.t. for 5 min, aryl halide (1 equiv) and amine (3 equiv) were added, the tube was returned under argon and capped. The reaction mixture was heated with stirring to 100 °C for the appropriate time. Products were purified by preparative column chromatography. N,N-Dimethyl-3-{(5H-pyrido[4,3-b][1]benzazepin-5-yl}propan-1-amine (10) Yield 81%; yellow oil. 1H NMR (500 MHz, CDCl3): δ = 8.35 (d, J = 5.5 Hz, 1 H), 8.17 (s, 1 H), 7.30–7.22 (m, 1 H), 7.05–6.98 (m, 2 H), 6.94 (d, J = 8.5 Hz, 1 H), 6.81 (d, J = 5.5 Hz, 1 H), 6.74 (d, J = 11.5 Hz, 1 H), 6.60 (d, J = 11.5 Hz, 1 H), 3.80–3.73 (m, 2 H), 2.39–2.33 (m, 2 H), 2.15 (s, 6 H), 1.82–1.70 (m, 2 H). 13C NMR (125 MHz, CDCl3): δ = 158.8, 150.5, 150.1, 149.1, 134.1, 133.6, 129.5, 129.3, 129.2, 129.1, 124.1, 121.1, 114.7, 57.1, 48.2, 45.5, 25.4. IR (ATR): 3413, 3023, 2944, 2858, 2817, 2767, 1635, 1578, 1481, 1419, 1392, 1332, 1244, 1184, 1123, 1060, 919, 831, 794, 766 cm–1. ESI-HRMS (+): m/z = 280.18125 [M + H]+ (error: 1.51 ppm).
- 24 Procedure for the Microwave Pd-Catalyzed Synthesis of Thiepines 18 and 19 A reaction tube containing a stirring bar was evacuated and backfilled with argon. The tube was charged with Pd(OAc)2 (5 mol%), dppf (10 mol%), NaOt-Bu (1.2 equiv), aryl halide (1 equiv), and KSAc (1.2 equiv) under argon. The flask was capped with a rubber septum, and toluene was added. The reaction mixture was heated in a Biotage Initiator 2.5 microwave at 175 °C for 90 min. After completion, the reaction mixture was cooled to r.t., and the products were purified by preparative column chromatography. [1]Benzothiepino[3,2-c]pyridine (18) Yield 51%; white solid; mp 80–82 °C. 1H NMR (500 MHz, CDCl3): δ = 8.48–8.44 (m, 2 H), 7.48–7.44 (m, 1 H), 7.36–7.28 (m, 3 H), 7.28–7.24 (m, 1 H), 7.13 (d, J = 12.5 Hz, 1 H), 6.99 (d, J = 12.5 Hz, 1 H). 13C NMR (125 MHz, CDCl3): δ = 149.9, 149.8, 144.7, 139.7, 136.1, 135.4, 133.0, 132.7, 130.4, 129.9, 129.7, 128.7, 126.3. IR (ATR): 3056, 3025, 2927, 2855, 1738, 1629, 1563, 1538, 1471, 1442, 1416, 1389, 1306, 1275, 1174, 1056, 885, 836 cm–1. ESI-HRMS (+): m/z = 212.05209 [M + H]+ (error: –3.58 ppm).