Synlett 2013; 24(8): 955-958
DOI: 10.1055/s-0032-1316899
letter
© Georg Thieme Verlag Stuttgart · New York

Approach to the Core Structure of the Polycyclic Alkaloid Palhinine A

Dominik Gaugele
Institut für Organische Chemie, Universität Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany   Fax: +49(7071)295137   Email: martin.e.maier@uni-tuebingen.de
,
Martin E. Maier*
Institut für Organische Chemie, Universität Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany   Fax: +49(7071)295137   Email: martin.e.maier@uni-tuebingen.de
› Author Affiliations
Further Information

Publication History

Received: 11 February 2013

Accepted after revision: 18 March 2013

Publication Date:
09 April 2013 (online)


Abstract

A synthesis of the tricyclic partly substituted core structure of palhinine A was achieved. To reach the bicyclo[2.2.2]octane motif a domino Michael reaction was employed as a key step. After Arndt–Eistert homologation and intramolecular aldol reaction the isotwistane core could be obtained after simple functional-group manipulations.

Supporting Information

Primary Data

 
  • References and Notes

  • 1 Zhao F.-W, Sun Q.-Y, Yang F.-M, Hu G.-W, Luo J.-F, Tang G.-H, Wang Y.-H, Long C.-L. Org. Lett. 2010; 12: 3922
  • 2 Zhao C, Zheng H, Jing P, Fang B, Xie X, She X. Org. Lett. 2012; 14: 2293
  • 3 Zhang G.-B, Wang F.-X, Du J.-Y, Qu H, Ma X.-Y, Wei M.-X, Wang C.-T, Li Q, Fan C.-A. Org. Lett. 2012; 14: 3696

    • For representative bimolecular domino Michael reactions, see:
    • 4a Lee RA. Tetrahedron Lett. 1973; 14: 3333
    • 4b White KB, Reusch W. Tetrahedron 1978; 34: 2439
    • 4c Roberts MR, Schlessinger RH. J. Am. Chem. Soc. 1981; 103: 724
    • 4d Gibbons EG. J. Am. Chem. Soc. 1982; 104: 1767
    • 4e Nagaoka H, Kobayashi K, Matsui T, Yamada Y. Tetrahedron Lett. 1987; 28: 2021
    • 4f Spitzner D, Engler A. Org. Synth. 1987; 66: 37 ; Org. Synth., Coll. Vol. VIII 1993, 219
    • 4g Iwashima M, Nagaoka H, Kobayashi K, Yamada Y. Tetrahedron Lett. 1992; 33: 81
    • 4h Hagiwara H, Yamada Y, Sakai H, Suzuki T, Ando M. Tetrahedron 1998; 54: 10999
    • 4i Hagiwara H, Sakai H, Kirita M, Hoshi T, Suzuki T, Ando M. Tetrahedron 2000; 56: 1445
    • 4j Spitzner D, Oesterreich K. Eur. J. Org. Chem. 2001; 1883
    • 4k Giardini A, Lesma G, Passarella D, Perez M, Silvani A. Synlett 2001; 132
    • 4l Hagiwara H, Endou S, Fukushima M, Hoshi T, Suzuki T. Org. Lett. 2004; 6: 1115
    • 4m Hua Z, Yu W, Su M, Jin Z. Org. Lett. 2005; 7: 1939
    • 4n Srikrishna A, Ravi G, Satyanarayana G. Tetrahedron Lett. 2007; 48: 73
    • 4o Fukushima M, Morii A, Hoshi T, Suzuki T, Hagiwara H. Tetrahedron 2007; 63: 7154
    • 4p Srikrishna A, Ravi G. Tetrahedron 2008; 64: 2565
    • 4q Komanduri V, Pedraza F, Krische MJ. Adv. Synth. Catal. 2008; 350: 1569
    • 4r Li W, Xiao Y, Zhang J. Adv. Synth. Catal. 2009; 351: 3083
    • 4s Yang J, Huang H, Jin Z, Wu W, Ye J. Synthesis 2011; 1984

      For representative intramolecular domino Michael reactions, see:
    • 5a Ihara M, Toyota M, Fukumoto K, Kametani T. Tetrahedron Lett. 1984; 25: 2167
    • 5b Ihara M, Ishida Y, Abe M, Toyota M, Fukumoto K, Kametani T. J. Chem. Soc., Perkin Trans. 1 1988; 1155
    • 5c Ihara M, Makita K, Fujiwara Y, Tokunaga Y, Fukumoto K. J. Org. Chem. 1996; 61: 6416
    • 5d Takasu K, Mizutani S, Noguchi M, Makita K, Ihara M. J. Org. Chem. 2000; 65: 4112
    • 5e Kuwahara S, Hamade S, Leal WS, Ishikawa J, Kodama O. Tetrahedron 2000; 56: 8111
    • 5f Kanoh N, Sakanishi K, Iimori E, Nishimura Ki, Iwabuchi Y. Org. Lett. 2011; 13: 2864
  • 6 For a review, see: Ihara M, Fukumoto K. Angew. Chem., Int. Ed. Engl. 1993; 32: 1010 ; Angew. Chem. 1993, 105, 1059
  • 7 Arndt F, Eistert B. Ber. Dtsch. Chem. Ges. 1935; 68: 200

    • For some reviews, see:
    • 8a Kirmse W. Eur. J. Org. Chem. 2002; 2193
    • 8b Zhang Z, Wang J. Tetrahedron 2008; 64: 6577
  • 9 Cahiez G, Alexakis A, Normant JF. Tetrahedron Lett. 1978; 19: 3013
    • 10a Hara R, Furukawa T, Kashima H, Kusama H, Horiguchi Y, Kuwajima I. J. Am. Chem. Soc. 1999; 121: 3072
    • 10b Yamada S, Suemune H. Chem. Pharm. Bull. 2000; 48: 1171
    • 10c Gulías M, Rodríguez JR, Castedo L, Mascareñas JL. Org. Lett. 2003; 5: 1975

      Addition reactions with Grignard reagents derived from ω-halohydrins:
    • 11a Conia J.-M, Rouessac F. Tetrahedron 1961; 16: 45
    • 11b Tietze LF, Schirok H, Wöhrmann M. Chem. Eur. J. 2000; 6: 510
    • 11c Findley TJ. K, Sucunza D, Miller LC, Davies DT, Procter DJ. Chem. Eur. J. 2008; 14: 6862

      Addition reactions with other Grignard reagents:
    • 12a Becker D, Harel Z, Nagler M, Gillon A. J. Org. Chem. 1982; 47: 3297
    • 12b Schinzer D. Angew. Chem., Int. Ed. Engl. 1984; 23: 308 ; Angew. Chem. 1984, 96, 292
  • 13 Mascaretti OA, Furlán RL. E. Aldrichimica Acta 1997; 30: 55
  • 14 Sheldrick GM. Acta Crystallogr., Sect. A: Found. Crystallogr. 2008; 64: 112
    • 15a Dess DB, Martin JC. J. Org. Chem. 1983; 48: 4155
    • 15b Meyer SD, Schreiber SL. J. Org. Chem. 1994; 59: 7549
    • 15c Boeckman RK. Jr, Shao P, Mullins JJ. Org. Synth. 2000; 77: 141 ; Org. Synth., Coll. Vol. X; 2004, 696
  • 16 Acetate 17 To a solution of tosylhydrazone 16 (182 mg, 270 μmol) in abs. MeOH (3 mL) were added anhyd ZnCl2 (44 mg, 703 μmol, 2.6 equiv) and NaCNBH3 (59 mg, 433 μmol, 1.6 equiv) at r.t. The reaction was then stirred at reflux temperature for 3.5 h. Then additional NaCNBH3 (59 mg, 433 μmol, 1.6 equiv) was added and reflux was continued for 2 h. Thereafter, the mixture was cooled to r.t. and treated with aq NaOH (10 mL, 1 M) and sat. NaCl solution (10 mL). The milky mixture was extracted with EtOAc (3 × 40 mL). The combined organic layers were dried over Na2SO4, filtered, concentrated in vacuo, and purified by flash chromatography (1.5 × 15 cm, PE–EtOAc, 10:1 to 0:1) to give 94 mg (192 μmol, 71%) of acetate 17 as a colorless oil; Rf = 0.63 (cyclohexane–EtOAc = 2:1). 1H NMR (400 MHz, CDCl3): δ = 1.05 (s, 9 H, H t-Bu), 1.16–1.31 (m, 2 H, 2′-H, 10-H), 1.35–1.64 (m, 9 H, 1-H, 1′-H, 2′-H, 5-H, 8-H, 9-H), 1.73–1.95 (m, 9 H, 2-H, 3-H, 5-H, 6-H, 10-H, CH3CO2), 3.56–3.69 (m, 2 H, 3′-H), 4.89–4.96 (m, 1 H, 4-H), 7.34–7.45 (m, 6 H, HAr), 7.65–7.70 (m, 4 H, HAr). 13C NMR (100 MHz, CDCl3): δ = 19.2 [C(CH3)3], 21.3 (CH3CO2), 24.0 (C-8), 24.0 (C-1), 26.9 [C(CH3)3], 27.3 (C-1′),28.6 (C-9), 33.2 (C-2′), 34.4 (C-5), 37.1 (C-10), 38.5 (C-6), 40.7 (C-7), 41.1 (C-2), 44.9 (C-3), 64.8 (C-3′), 85.3 (C-4), 127.6 (CAr), 129.5 (CAr), 134.1 (CAr), 134.1 (CAr), 135.5 (CAr), 170.9 (CH3 CO2). HRMS: calcd for C31H42O3Si [M + Na]+: 513.279543; found: 513.279442.
  • 17 Taber DF, Wang Y, Stachel SJ. Tetrahedron Lett. 1993; 34: 6209
  • 18 Ketone 5 To a solution of alcohol 18 (58 mg, 129 μmol) in abs. CH2Cl2 (1.3 mL) were added NaHCO3 (43 mg, 517 μmol, 4 equiv) and DMP (71 mg, 168 μmol, 1.3 equiv) at r.t. After 1 h at r.t. DMP (71 mg, 168 μmol, 1.3 equiv) was added. After additional 30 min at r.t. sat. aq NaHCO3 solution (2 mL) and sat. aq Na2S2O3 solution (2 mL) were added, and the mixture was stirred for 30 min. H2O (5 mL) was added, and the mixture was extracted with Et2O (3 × 15 mL). The combined organic layers were washed with sat. NaCl solution (10 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (1.5 × 15 cm, PE–EtOAc = 8:1) to give 51 mg (114 μmol, 88%) of tricyclic ketone 5 as a colorless oil; Rf = 0.45 (cyclohexane–EtOAc, 5:1). 1H NMR (400 MHz, CDCl3): δ = 1.04 (s, 9 H, H t-Bu), 1.08–1.28 (m, 2 H, 1′-H), 1.36–1.72 (m, 9 H, 1-H, 2-H, 2′-H, 8-H, 9-H, 10-H), 1.79–2.05 (m, 4 H, 2-H, 3-H, 5-H, 10-H), 2.13–2.21 (m, 1 H, 6-H), 2.42 (dd, J = 7.2, 18.8 Hz, 1 H, 5-H), 3.53–3.66 (m, 2 H, 3′-H), 7.33–7.46 (m, 6 H, HAr), 7.60–7.68 (m, 4 H, HAr). 13C NMR (100 MHz, CDCl3): δ = 19.1 [C(CH3)3], 24.0 (C-8), 24.3 (C-1), 26.8 [C(CH3)3], 27.1 (C-2′), 28.0 (C-9), 30.5 (C-2), 33.7 (C-1′), 35.0 (C-6), 36.5 (C-10), 38.6 (C-7), 45.4 (C-5), 51.5 (C-3), 64.1 (C-3′), 127.6 (CAr), 129.5 (CAr), 133.9 (CAr), 135.5 (CAr), 222.4 (C-4). HRMS: m/z calcd for C29H38O2Si [M + Na]+: 469.253328; found: 469.253565.