PDF herunterladen
Synlett 2012; 23(11): 1691-1695
DOI: 10.1055/s-0031-1291162
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of 3-Aroyl-4-hydroxy-4-arylpiperidine Derivatives by DBU-Catalyzed Reactions of Amines with Vinyl Ketones

Xiaodong Liu
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Science, Institute of Biochemistry and Molecular Biology School of Life Science, Lanzhou University, Lanzhou 730000, P. R. of China, Fax: +86(931)8912567   eMail: wangrui@lzu.edu.cn
,
Qiao Chen
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Science, Institute of Biochemistry and Molecular Biology School of Life Science, Lanzhou University, Lanzhou 730000, P. R. of China, Fax: +86(931)8912567   eMail: wangrui@lzu.edu.cn
,
Wenyi Li
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Science, Institute of Biochemistry and Molecular Biology School of Life Science, Lanzhou University, Lanzhou 730000, P. R. of China, Fax: +86(931)8912567   eMail: wangrui@lzu.edu.cn
,
Yuan Liang
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Science, Institute of Biochemistry and Molecular Biology School of Life Science, Lanzhou University, Lanzhou 730000, P. R. of China, Fax: +86(931)8912567   eMail: wangrui@lzu.edu.cn
,
Rui Wang*
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Science, Institute of Biochemistry and Molecular Biology School of Life Science, Lanzhou University, Lanzhou 730000, P. R. of China, Fax: +86(931)8912567   eMail: wangrui@lzu.edu.cn
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received: 14. März 2012

Accepted after revision: 16. April 2012

Publikationsdatum:
11. Juni 2012 (online)

    Lizenzen und Reprints Alle Artikel dieser Rubrik


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.

Key words

Michael addition - vinyl ketones - cascade reaction - cyclization - stereoselectivity

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 Data
 

  • 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
      Crossref
    • 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
      Crossref
    • 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
      Crossref
    • 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
      Crossref
    • 2b Cwik A, Fuchs A, Hell Z, Clacens JM. J. Mol. Catal. A: Chem. 2004; 219: 377
      Crossref
    • 2c Vashishtha SC, Zello GA, Nienaber KH, Balzarini J, Clercq ED, Stables JP, Dimmock JR. Eur. J. Med. Chem. 2004; 39: 27
      Crossref
    • 2d Upton C, Osborne RH, Jaffar M. Bioorg. Med. Chem. Lett. 2000; 10: 1277
      Crossref
    • 3a Joensuu PM, Murray GJ, Fordyce EA. F, Luebbers T, Lam HW. J. Am. Chem. Soc. 2008; 130: 7328
      CrossrefPubMed
    • 3b Lam HW, Joensuu PM, Murray GJ, Fordyce EA. F. Prieto O, Luebbers T. Org. Lett. 2006; 8: 3729
      CrossrefPubMed
    • 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
      Crossref
    • 3d See also: Liu XD, Deng LJ, Song HJ, Jia HZ, Wang R. Org. Lett. 2011; 13: 1494
      Crossref
    • 3e See also: Jiang XX, Cao YM, Wang YQ, Liu LP, Shen FF, Wang R. J. Am. Chem. Soc. 2010; 132: 15328
      CrossrefPubMed
    • 3f See also: Liu XD, Deng LJ, Jiang XX, Yan WJ, Liu CL, Wang R. Org. Lett. 2010; 12: 876
      Crossref

      For selected reviews of domino reactions, see:
    • 4a Grondal C, Jeanty M, Enders D. Nature Chem. 2010; 2: 167
      CrossrefPubMed
    • 4b Davies HM. L, Sorensen EJ. Chem. Soc. Rev. 2009; 38: 2981
      Crossref
    • 4c Kim J, Movassaghi M. Chem. Soc. Rev. 2009; 38: 3035
      CrossrefPubMed
    • 4d Nicolaou KC, Chen JS. Chem. Soc. Rev. 2009; 38: 2993
      CrossrefPubMed
    • 4e Young IS, Baran PS. Nature Chem. 2009; 1: 193
      Crossref
    • 4f Burns NZ, Baran PS, Hoffmann RW. Angew. Chem. Int. Ed. 2009; 48: 2854
      CrossrefPubMed
    • 4g Newhouse T, Baran PS, Hoffmann RW. Chem. Soc. Rev. 2009; 38: 3010
      CrossrefPubMed
    • 4h Wender PA, Verma VA, Paxton TJ, Pillow TH. Acc. Chem. Res. 2008; 41: 40
      CrossrefPubMed
    • 4i Bulger PG, Bagal SK, Marquez R. Nat. Prod. Rep. 2008; 25: 254
      CrossrefPubMed
    • 4j Yua X.-H, Wang W. Org. Biomol. Chem. 2008; 6: 2037
      Crossref
    • 4k Chapman CJ, Frost CG. Synthesis 2007; 1
      Artikel in Thieme Connect
    • 4l Nicolaou KC, Edmonds DJ, Bulger PG. Angew. Chem. Int. Ed. 2006; 45: 7134
      CrossrefPubMed
    • 4m Guo H.-C, Ma J.-A. Angew. Chem. Int. Ed. 2006; 45: 354
      CrossrefPubMed
    • 4n Pellissier H. Tetrahedron 2006; 62: 2143
      Crossref
    • 4o Tietze LF, Brasche G, Gericke K. Domino Reactions in Organic Synthesis . Wiley-VCH; Weinheim: 2006
      CrossrefGoogle Scholar
    • 5a Sun FG, Huang XL, Ye S. J. Org. Chem. 2010; 75: 273
      Crossref
    • 5b Rueping M, Antonchick AP. Angew. Chem. Int. Ed. 2008; 47: 5836
      CrossrefPubMed
    • 5c Xie H.-X, Zu L.-S, Li H, Wang J, Wang W. J. Am. Chem. Soc. 2007; 129: 10886
      Crossref
    • 5d Zu L.-S, Li H, Xie H.-X, Wang J, Jiang W, Tang Y, Wang W. Angew. Chem. Int. Ed. 2007; 46: 3732
      Crossref
    • 5e Rueping M, Antonchick AP. Angew. Chem. Int. Ed. 2007; 46: 4562
      CrossrefPubMed
    • 5f Wang W, Li H, Wang J, Zu L.-S. J. Am. Chem. Soc. 2006; 128: 10354
      CrossrefPubMed
    • 5g Rueping M, Antonchick AP, Theissmann T. Angew. Chem. Int. Ed. 2006; 45: 3683
      CrossrefPubMed
    • 5h Rueping M, Azap C. Angew. Chem. Int. Ed. 2006; 45: 7832
      CrossrefPubMed
    • 6a Bunce RA, Nago T. J. Heterocycl. Chem. 2009; 46: 623
      Crossref
    • 6b Herath A, Thompson BB, Montgomery J. J. Am. Chem. Soc. 2007; 129: 8712
      Crossref
    • 6c Herath A, Montgomery J. J. Am. Chem. Soc. 2006; 128: 14030
      Crossref
    • 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