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 2012; 23(11): 1691-1695
DOI: 10.1055/s-0031-1291162
DOI: 10.1055/s-0031-1291162
letter
Synthesis of 3-Aroyl-4-hydroxy-4-arylpiperidine Derivatives by DBU-Catalyzed Reactions of Amines with Vinyl Ketones
Further Information
Publication History
Received: 14 March 2012
Accepted after revision: 16 April 2012
Publication Date:
11 June 2012 (online)
![](https://www.thieme-connect.de/media/synlett/201211/lookinside/thumbnails/10.1055-s-0031-1291162-1.jpg)
Abstract
In one-pot cascade reaction, a series of functionalized 3-aroyl-4-hydroxy-4-arylpiperidine derivatives were prepared from sulfonamides and vinyl ketones with good to excellent yields and diastereoselectivities. The reaction was catalyzed by the commercially available Lewis base 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and could be easily manipulated under mild condition.
Supporting Information
- for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
- Supporting Information
Primary Data
- for this article are available online at http://www.thieme-connect.com/ejournals/toc/synlett and can be cited using the following DOI:
- Primary Dat
-
References and Notes
- 1a Gul HI, Calis U, Vepsalainen J. Arzneim.-Forsch. 2002; 12: 863
- 1b Wang S, Sakamuri S, Enyedy IJ, Kozikowski AP, Zaman WA, Johnson KM. Bioorg. Med. Chem. 2001; 9: 1753
- 1c Wang S, Sakamuri S, Enyedy IJ, Kozikowski AP, Deschaux O, Bandyopadhyay BC, Tella SR, Zaman WZ, Johnson KM. J. Med. Chem. 2000; 43: 351
- 1d Dimmock JR, Vashishta SC, Quail JW, Pugazhenthi U, Zimpel Z, Sudom AM, Allen TM, Kao GY, Balzarini JE, De Clercq E. J. Med. Chem. 1998; 41: 4012
- 2a Lansdell MI, Hepworth D, Calabrese A, Brown AD, Blagg J, Burring DJ, Wilson P, Fradet D, Brown TB, Quinton F, Mistry N, Tang K, Mount N, Stacey P, Edmunds N, Adams C, Gaboardi S, Neal-Morgan S, Wayman C, Cole S, Phipps J, Lewis M, Verrier H, Gillon V, Feeder N, Heatherington A, Sultana S, Haughie S, Martin SW, Sudworth M, Tweedy S. J. Med. Chem. 2010; 53: 3183
- 2b Cwik A, Fuchs A, Hell Z, Clacens JM. J. Mol. Catal. A: Chem. 2004; 219: 377
- 2c Vashishtha SC, Zello GA, Nienaber KH, Balzarini J, Clercq ED, Stables JP, Dimmock JR. Eur. J. Med. Chem. 2004; 39: 27
- 2d Upton C, Osborne RH, Jaffar M. Bioorg. Med. Chem. Lett. 2000; 10: 1277
- 3a Joensuu PM, Murray GJ, Fordyce EA. F, Luebbers T, Lam HW. J. Am. Chem. Soc. 2008; 130: 7328
- 3b Lam HW, Joensuu PM, Murray GJ, Fordyce EA. F. Prieto O, Luebbers T. Org. Lett. 2006; 8: 3729
- 3c For selected examples with heterocycle reactions in our group, see: Sun WS, Zhu GM, Hong L, Wang R. Chem. Eur. J. 2011; 17: 13958
- 3d See also: Liu XD, Deng LJ, Song HJ, Jia HZ, Wang R. Org. Lett. 2011; 13: 1494
- 3e See also: Jiang XX, Cao YM, Wang YQ, Liu LP, Shen FF, Wang R. J. Am. Chem. Soc. 2010; 132: 15328
- 3f See also: Liu XD, Deng LJ, Jiang XX, Yan WJ, Liu CL, Wang R. Org. Lett. 2010; 12: 876
- 4a Grondal C, Jeanty M, Enders D. Nature Chem. 2010; 2: 167
- 4b Davies HM. L, Sorensen EJ. Chem. Soc. Rev. 2009; 38: 2981
- 4c Kim J, Movassaghi M. Chem. Soc. Rev. 2009; 38: 3035
- 4d Nicolaou KC, Chen JS. Chem. Soc. Rev. 2009; 38: 2993
- 4e Young IS, Baran PS. Nature Chem. 2009; 1: 193
- 4f Burns NZ, Baran PS, Hoffmann RW. Angew. Chem. Int. Ed. 2009; 48: 2854
- 4g Newhouse T, Baran PS, Hoffmann RW. Chem. Soc. Rev. 2009; 38: 3010
- 4h Wender PA, Verma VA, Paxton TJ, Pillow TH. Acc. Chem. Res. 2008; 41: 40
- 4i Bulger PG, Bagal SK, Marquez R. Nat. Prod. Rep. 2008; 25: 254
- 4j Yua X.-H, Wang W. Org. Biomol. Chem. 2008; 6: 2037
- 4k Chapman CJ, Frost CG. Synthesis 2007; 1
- 4l Nicolaou KC, Edmonds DJ, Bulger PG. Angew. Chem. Int. Ed. 2006; 45: 7134
- 4m Guo H.-C, Ma J.-A. Angew. Chem. Int. Ed. 2006; 45: 354
- 4n Pellissier H. Tetrahedron 2006; 62: 2143
- 4o Tietze LF, Brasche G, Gericke K. Domino Reactions in Organic Synthesis . Wiley-VCH; Weinheim: 2006
- 5a Sun FG, Huang XL, Ye S. J. Org. Chem. 2010; 75: 273
- 5b Rueping M, Antonchick AP. Angew. Chem. Int. Ed. 2008; 47: 5836
- 5c Xie H.-X, Zu L.-S, Li H, Wang J, Wang W. J. Am. Chem. Soc. 2007; 129: 10886
- 5d Zu L.-S, Li H, Xie H.-X, Wang J, Jiang W, Tang Y, Wang W. Angew. Chem. Int. Ed. 2007; 46: 3732
- 5e Rueping M, Antonchick AP. Angew. Chem. Int. Ed. 2007; 46: 4562
- 5f Wang W, Li H, Wang J, Zu L.-S. J. Am. Chem. Soc. 2006; 128: 10354
- 5g Rueping M, Antonchick AP, Theissmann T. Angew. Chem. Int. Ed. 2006; 45: 3683
- 5h Rueping M, Azap C. Angew. Chem. Int. Ed. 2006; 45: 7832
- 6a Bunce RA, Nago T. J. Heterocycl. Chem. 2009; 46: 623
- 6b Herath A, Thompson BB, Montgomery J. J. Am. Chem. Soc. 2007; 129: 8712
- 6c Herath A, Montgomery J. J. Am. Chem. Soc. 2006; 128: 14030
- 6d Maezaki N, Sawamoto H, Ishihara H, Tanaka T. Chem. Commun. 2005; 3992
-
6e Montgomery J, Oblinger E, Savchenko AV. J. Am. Chem. Soc. 1997; 119: 4911
- 7 CCDC 857042 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif
- 8 General Procedure for the Cascade Reaction: To a mixture of amines 1 (0.2 mmol) and vinyl ketones 2 (0.45 mmol) in toluene (1.0 mL) was added DBU (0.04 mmol) at room temperature. After 6–8 h the reaction was complete (as determined by TLC). The reaction mixture was concentrated and the residue was purified by flash chromatography (petroleum ether/ethyl acetate, 5:1) to afford the product 6. The analytical data of some typical compounds: Compound 6b: White solid; m.p.179–180 °C. 1H NMR (300 MHz, CDCl3): δ = 7.69 (d, J = 8.1 Hz, 2 H), 7.57 (dd, J = 7.7, 1.1 Hz, 1 H), 7.36 (dd, J = 13.7, 5.1 Hz, 3 H), 7.09 (t, J = 7.1 Hz, 1 H), 6.98–6.81 (m, 2 H), 6.78–6.63 (m, 2 H), 6.50 (d, J = 8.1 Hz, 1 H), 5.08 (dd, J = 11.4, 3.7 Hz, 1 H), 4.47 (d, J = 2.4 Hz, 1 H), 4.14 (dd, J = 10.6, 2.3 Hz, 1 H), 4.02 (s, 3 H), 3.76–3.67 (m, 1 H), 3.42 (s, 3 H), 2.92 (ddd, J = 11.0, 7.4, 3.2 Hz, 2 H), 2.74–2.52 (m, 1 H), 2.44 (s, 3 H), 1.57 (d, J = 13.6 Hz, 1 H). 13C NMR (75 MHz, CDCl3): δ = 207.6, 158.6, 155.6, 143.5, 133.9, 133.5, 132.4, 129.8, 129.2, 129.0, 128.7, 127.6, 127.5, 120.7, 120.5, 111.0, 110.7, 72.5, 55.8, 54.5, 51.9, 44.0, 42.3, 34.7, 21.6. IR (CDCl3): 3459, 2926, 1648, 1592, 1456, 1319, 1160, 913, 729, 573 cm–1. HRMS (ESI): m/z calcd for C27H29NO6S+Na+: 518.1608; found: 518.1587. Compound 6d: White solid; m.p. 162–163 °C. 1H NMR (300 MHz, CDCl3): δ = 7.96 (t, J = 1.6 Hz, 1 H), 7.74 (d, J = 7.9 Hz, 2 H), 7.58 (dd, J = 7.8, 1.6 Hz, 1 H), 7.51–7.31 (m, 2 H), 7.15–7.04 (m, 1 H), 6.91 (t, J = 8.4 Hz, 2 H), 6.80–6.62 (m, 2 H), 6.51 (d, J = 8.1 Hz, 1 H), 5.08 (dd, J = 11.4, 3.8 Hz, 1 H), 4.50 (d, J = 2.7 Hz, 1 H), 4.15 (dd, J = 11.0, 2.4 Hz, 1 H), 4.04 (s, 3 H), 3.82–3.66 (m, 1 H), 3.42 (s, 3 H), 3.00 (td, J = 11.1, 4.8 Hz, 2 H), 2.70–2.51 (m, 1 H), 1.60 (d, J = 13.6 Hz, 1 H). 13C NMR (75 MHz, CDCl3): δ = 207.4, 158.6, 155.5, 138.7, 135.8, 133.9, 132.2, 130.7, 130.3, 129.2, 128.9, 128.7, 127.5, 126.0, 123.3, 120.7, 120.5, 111.0, 110.7, 72.5, 55.8, 54.6, 51.8, 43.9, 42.3, 34.6. IR (CDCl3): 3432, 2934, 1655, 1597, 1462, 1245, 1166, 1022, 757, 580 cm–1. HRMS (ESI): m/z calcd for C26H26BrNO6S+H+: 560.0737; found: 560.0738. Compound 6e: White solid; m.p. 177–178 °C. 1H NMR (300 MHz, CDCl3): δ = 7.80–7.69 (m, 2 H), 7.57 (dd, J = 7.8, 1.7 Hz, 1 H), 7.41–7.31 (m, 1 H), 7.09 (td, J = 8.1, 1.7 Hz, 1 H), 7.05–6.98 (m, 2 H), 6.94–6.83 (m, 2 H), 6.72 (qd, J = 7.6, 1.4 Hz, 2 H), 6.55–6.41 (m, 1 H), 5.08 (dd, J = 11.4, 3.8 Hz, 1 H), 4.47 (d, J = 2.7 Hz, 1 H), 4.17–4.11 (m, 1 H), 4.02 (s, 3 H), 3.88 (s, 3 H), 3.75–3.65 (m, 1 H), 3.42 (s, 3 H), 3.01–2.81 (m, 2 H), 2.63 (tdd, J = 13.1, 4.8, 2.8 Hz, 1 H), 1.57 (dd, J = 11.2, 2.3 Hz, 1 H). 13C NMR (75 MHz, CDCl3): δ = 207.6, 162.9, 158.6, 155.5, 133.9, 132.4, 129.6, 129.2, 129.0, 128.7, 128.0, 127.4, 120.6, 120.5, 114.3, 111.0, 110.7, 72.5, 55.8, 55.6, 54.5, 51.8, 44.0, 42.3, 34.7. IR (CDCl3): 3454, 2936, 1656, 1597, 1254, 1159, 1023, 756, 559 cm–1. HRMS (ESI): m/z calcd for C27H29NO7S+Na+: 534.1557; found: 534.1568. Compound 6i: White solid; m.p. 95–96 °C. 1H NMR (300 MHz, CDCl3): δ = 7.99–7.81 (m, 2 H), 7.59–7.46 (m, 3 H), 7.41 (dd, J = 10.5, 4.7 Hz, 2 H), 7.27–7.21 (m, 2 H), 7.13 (ddd, J = 7.3, 3.8, 1.2 Hz, 1 H), 5.16 (d, J = 2.7 Hz, 1 H), 4.40 (d, J = 8.0 Hz, 1 H), 3.04–2.83 (m, 2 H), 2.69 (t, J = 11.4 Hz, 2 H), 2.44 (dd, J = 8.6, 7.2 Hz, 2 H), 2.07 (t, J = 12.8 Hz, 1 H), 1.82 (dt, J = 13.9, 2.6 Hz, 1 H), 1.64–1.46 (m, 2 H), 0.92 (t, J = 7.4 Hz, 3 H). 13C NMR (75 MHz, CDCl3): δ = 204.46, 147.21, 137.03, 135.90, 133.93, 133.05, 128.81, 128.60, 128.34, 128.28, 128.08, 126.76, 124.57, 73.16, 60.46, 52.83, 50.51, 49.17, 39.86, 20.15, 12.03. IR (CDCl3): 3458, 2959, 2929, 2818, 1663, 1448, 1377, 1205, 1070, 701 cm–1. HRMS (ESI): m/z calcd for C21H25NO2+H: 324.1958; found: 324.1959
- 9 The analytical data of some typical compounds: Compound 6k: White solid; m.p. 197–198 °C. 1H NMR (300 MHz, CDCl3): δ = 7.73–7.56 (m, 4 H), 7.43–7.29 (m, 4 H), 7.23 (s, 1 H), 7.18–7.02 (m, 2 H), 6.93 (d, J = 7.1 Hz, 1 H), 4.95 (d, J = 2.6 Hz, 1 H), 4.38 (dd, J = 11.5, 3.8 Hz, 1 H), 3.94 (dd, J = 11.6, 2.3 Hz, 1 H), 3.85–3.66 (m, 1 H), 3.04–2.79 (m, 2 H), 2.44 (s, 3 H), 2.38 (s, 3 H), 2.25 (s, 3 H), 2.18–2.06 (m, 1 H), 1.82 (d, J = 14.0 Hz, 1 H). 13C NMR (75 MHz, CDCl3): δ = 203.4, 145.8, 143.9, 138.9, 138.0, 135.6, 135.3, 133.4, 129.9, 128.9, 128.9, 128.3, 127.9, 127.6, 125.7, 125.3, 121.4, 72.7, 49.5, 45.3, 42.5, 39.1, 21.6, 21.4. IR (CDCl3): 3443, 2925, 1654, 1584, 1387, 1341, 1280, 1163, 924, 545 cm–1. HRMS (ESI): m/z calcd for C27H29NO4S+Na+: 486.1710; found: 486.1689. Compound 6n: White solid; m.p. 192–193 °C. 1H NMR (300 MHz, CDCl3): δ = 8.50 (s, 1 H), 7.96 (d, J = 6.6 Hz, 2 H), 7.83–7.63 (m, 8 H), 7.55 (p, J = 6.7 Hz, 3 H), 7.40–7.27 (m, 4 H), 5.27 (d, J = 2.3 Hz, 1 H), 4.74 (dd, J = 11.4, 3.6 Hz, 1 H), 4.18–4.03 (m, 1 H), 3.88 (d, J = 11.2 Hz, 1 H), 3.08 (ddd, J = 16.1, 8.0, 4.0 Hz, 2 H), 2.41 (s, 3 H), 2.35–2.21 (m, 1 H), 1.92 (d, J = 14.0 Hz, 1 H). 13C NMR (75 MHz, CDCl3): δ = 203.0, 143.9, 143.3, 136.1, 133.4, 133.1, 132.7, 132.4, 132.4, 131.0, 130.0, 129.9, 129.4, 129.0, 128.4, 128.2, 127.8, 127.7, 127.4, 127.2, 126.2, 126.0, 123.7, 123.4, 122.6, 73.1, 49.4, 45.6, 42.6, 39.2, 21.6. IR (CDCl3): 3443, 3058, 2924, 1655, 1345, 1163, 922, 730, 549 cm–1. HRMS (ESI): m/z calcd for C33H29NO4S+Na+: 558.1710; found: 558.1716. Compound 6o: White solid; m.p. 159–160 °C. 1H NMR (300 MHz, CDCl3): δ = 7.66 (dd, J = 12.1, 3.9 Hz, 3 H), 7.60–7.52 (m, 2 H), 7.46–7.36 (m, 3 H), 7.24 (m, 7 H), 6.69 (dd, J = 30.5, 16.0 Hz, 2 H), 6.15 (d, J = 15.9 Hz, 1 H), 4.54 (d, J = 2.4 Hz, 1 H), 3.86 (dd, J = 11.5, 2.6 Hz, 1 H), 3.73 (dd, J = 9.4, 2.0 Hz, 1 H), 3.48 (dd, J = 11.6, 3.9 Hz, 1 H), 2.88–2.71 (m, 2 H), 2.44 (s, 3 H), 2.00–1.84 (m, 1 H), 1.75 (d, J = 15.2 Hz, 1 H). 13C NMR (75 MHz, CDCl3): δ = 202.3, 146.1, 143.9, 136.3, 133.8, 133.6, 133.0, 131.6, 129.9, 129.5, 129.1, 128.9, 128.5, 127.7, 127.6, 126.6, 125.4, 71.0, 52.0, 44.4, 41.9, 36.6, 21.6. IR (CDCl3): 3451, 3029, 2926, 2253, 1598, 1339, 1160, 1091, 919, 733 cm–1. HRMS (ESI): m/z calcd for C29H29NO4S+Na+: 510.1735; found: 510.1713. Compound 6p: White solid; m.p. 83–85 °C. 1H NMR (300 MHz, CDCl3): δ = 7.62 (d, J = 8.2 Hz, 2 H), 7.32 (d, J = 8.1 Hz, 2 H), 3.75–3.50 (m, 3 H), 2.97 (dd, J = 11.6, 3.8 Hz, 1 H), 2.80–2.47 (m, 4 H), 2.43 (s, 3 H), 1.68 (dd, J = 11.2, 2.5 Hz, 1 H), 1.60–1.51 (m, 1 H), 1.41 (dtd, J = 28.6, 14.2, 7.2 Hz, 2 H), 1.05 (t, J = 7.2 Hz, 3 H), 0.86 (t, J = 7.5 Hz, 3 H). 13C NMR (75 MHz, CDCl3): δ = 215.9, 143.8, 132.9, 129.8, 127.6, 70.5, 53.6, 44.2, 41.9, 38.3, 33.7, 33.3, 21.5, 7.6, 7.1. IR (CDCl3): 3488, 2971, 2930, 1696, 1343, 1161, 921, 744, 548 cm–1. HRMS (ESI): m/z calcd for C17H25NO4S+H+: 340.1577; found: 340.1587
- 10 CCDC 857043 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif
For selected reviews of domino reactions, see: