Synlett 2014; 25(20): 2953-2956
DOI: 10.1055/s-0034-1379485
letter
© Georg Thieme Verlag Stuttgart · New York

Magnesium-Coordinated Chelation Control in 1,3-Dipolar Cycloaddition of Chiral α-Alkoxymethyl Ether Nitrile Oxide: Application to the Synthesis of (–)/(–)-cis-Clausenamide

Kazuhiro Tanda*
Department of Pharmaceutical Chemistry, Kyushu University of Health and Welfare, 1714-1 Yoshino, Nobeoka, Miyazaki 882-8508, Japan   Fax: +81(982)235711   Email: tanda@phoenix.ac.jp   Email: tetsuyam@phoenix.ac.jp
,
Atsushi Toyao
Department of Pharmaceutical Chemistry, Kyushu University of Health and Welfare, 1714-1 Yoshino, Nobeoka, Miyazaki 882-8508, Japan   Fax: +81(982)235711   Email: tanda@phoenix.ac.jp   Email: tetsuyam@phoenix.ac.jp
,
Akiko Watanabe
Department of Pharmaceutical Chemistry, Kyushu University of Health and Welfare, 1714-1 Yoshino, Nobeoka, Miyazaki 882-8508, Japan   Fax: +81(982)235711   Email: tanda@phoenix.ac.jp   Email: tetsuyam@phoenix.ac.jp
,
Masanori Sakamoto
Department of Pharmaceutical Chemistry, Kyushu University of Health and Welfare, 1714-1 Yoshino, Nobeoka, Miyazaki 882-8508, Japan   Fax: +81(982)235711   Email: tanda@phoenix.ac.jp   Email: tetsuyam@phoenix.ac.jp
,
Tetsuo Yamasaki*
Department of Pharmaceutical Chemistry, Kyushu University of Health and Welfare, 1714-1 Yoshino, Nobeoka, Miyazaki 882-8508, Japan   Fax: +81(982)235711   Email: tanda@phoenix.ac.jp   Email: tetsuyam@phoenix.ac.jp
› Author Affiliations
Further Information

Publication History

Received: 29 August 2014

Accepted after revision: 30 September 2014

Publication Date:
06 November 2014 (online)


Abstract

A facile regio- and diastereoselective nitrile oxide cycloaddition method using magnesium-coordinated chelation control of chiral α-alkoxymethyl ether nitrile oxide is reported. This reaction could be successfully applied as a key step in both the formal total synthesis of (–)-clausenamide and the total synthesis of (–)-cis-clausenamide.

 
  • References and Notes

    • 2a Gothelf KV, Jørgensen KA. Chem. Rev. 1998; 98: 863

    • For chiral catalysis and/or auxiliaries in nitrile oxide cycloadditions, see:
    • 2b Ukaji Y, Inomata K. Synlett 2003; 1075
    • 2c Sibi MP, Itoh K, Jasperse CP. J. Am. Chem. Soc. 2004; 126: 5366
    • 2d Sibi MP, Ma Z, Itoh K, Prabagran N, Jasperse CP. Org. Lett. 2005; 7: 2349
    • 2e Yamamoto H, Hayashi S, Kubo M, Harada M, Hasegawa M, Noguchi M, Sumitomo M, Hori K. Eur. J. Org. Chem. 2007; 2859
    • 2f Brinkmann Y, Madhushaw RJ, Jazzar R, Bernardinelli G, Kündig EP. Tetrahedron 2007; 63: 8413
    • 2g Suga H, Adachi Y, Fujimoto K, Furihata Y, Tsuchida T, Kakehi A, Baba T. J. Org. Chem. 2009; 74: 1099
    • 3a Kanemasa S, Nishiuchi M, Kamimura A, Hori K. J. Am. Chem. Soc. 1994; 116: 2324
    • 3b Kanemasa S, Okuda K, Yamamoto H, Kaga S. Tetrahedron Lett. 1997; 38: 4095
    • 3c Kanemasa S. Synlett 2003; 1371
    • 4a Bode JW, Fraefel N, Muri D, Carreira EM. Angew. Chem. Int. Ed. 2001; 40: 2082
    • 4b Bode JW, Carreira EM. J. Am. Chem. Soc. 2001; 123: 3611
    • 4c Bode JW, Carreira EM. J. Org. Chem. 2001; 66: 6410
    • 4d Fader LD, Carreira EM. Org. Lett. 2004; 6: 2485
    • 4e Muri D, Lohse N, Carreira EM. Angew. Chem. Int. Ed. 2005; 44: 4036
    • 4f Becker N, Carreira EM. Org. Lett. 2007; 9: 3857
    • 5a Chen YR, Yang MH, Huang L, Liu G, Benz U. Ger. Offen. DE3431257 Appl. Aug 24, 1984 ; Chem. Abstr. 1986, 105, 72689r.
    • 5b Feng Z, Li X, Zheng G, Huang L. Bioorg. Med. Chem. Lett. 2009; 19: 2112
  • 6 Li X, Zhu C, Li C, Wu K, Huang D, Huang L. Eur. J. Med. Chem. 2010; 45: 5531

    • For previous syntheses of these compounds, see:
    • 7a Hartwig W, Born L. J. Org. Chem. 1987; 52: 4352
    • 7b Huang DF, Huang L. Tetrahedron 1990; 46: 3135
    • 7c Yakura T, Matsumura Y, Ikeda M. Synlett 1991; 343
    • 7d Cappi MW, Chen W.-P, Flood RW, Liao Y.-W, Roberts SM, Skidmore J, Smith JA, Williamson NM. Chem. Commun. 1998; 1159
    • 7e Yang L, Wang D.-X, Zheng Q.-Y, Pan J, Huang Z.-T, Wang M.-X. Org. Biomol. Chem. 2009; 7: 2628
    • 7f Zhang L, Zhou Y, Yu X. Synlett 2012; 1217
    • 7g Xuan Y.-N, Lin H.-S, Yan M. Org. Biomol. Chem. 2013; 11: 1815
  • 8 All hydroximoyl chlorides expect for 4d are stable under prolonged storage.
  • 9 We obtained (E)-cinnamyl alcohol 3 by the Luche reduction of (E)-cinnamaldehyde, see: Gemal AL, Luche J.-L. J. Am. Chem. Soc. 1981; 103: 5454
  • 10 1,3-Dipolar Cycloaddition of Cinnamyl Alcohol (3) with α-Hydroxy-Protected Nitrile Oxides; Typical Procedure for 4c: To a solution of the (E)-cinnamyl alcohol (3) (796 mg, 5.94 mmol) and i-PrOH (1.50 mL, 17.8 mmol) in CH2Cl2 (187 mL) was added EtMgBr (1.0 mol/L in THF, 17.8 mL, 17.8 mmol) at 0 °C. The resulting mixture was stirred for 30 min at 0 °C. At this time, hydroximoyl chloride 4c (1.50 g, 6.53 mmol) in CH2Cl2 (100 mL) was added to the reaction dropwise by using a dropping funnel over 20 min, followed by two rinses with CH2Cl2 (5 mL each). The reaction mixture was stirred for 12 h and gently warmed to r.t., then the reaction was quenched with sat. aq NH4Cl solution. The organic layer was separated and the aqueous layer was extracted with CH2Cl2 (3 × 40 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by silica gel column flash chromatography (hexane–EtOAc, 1:1) to give cycloadducts 5c/5c' (1.81 g, 85%) as a yellow oil. d.r. = 75:25 [integration of signals at δ = 5.40 (major) and 5.28 (minor) ppm in the 1H NMR spectrum]. Major Cycloadduct 5c: [α]D 27 –160.7 (c 1.00, CHCl3). IR (film): 3428, 3060, 3028, 2945, 2889, 2825, 1604, 1494, 1455, 1151, 1094, 1035, 902, 753 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.36–7.27 (m, 8 H), 7.17 (d, J = 6.8 Hz, 2 H), 5.40 (s, 1 H), 4.58 (dd, J = 5.6, 3.6 Hz, 1 H), 4.32 (dd, J = 60.4, 6.8 Hz, 2 H), 4.19 (d, J = 6.0 Hz, 1 H), 3.73–3.68 (m, 1 H), 3.59–3.53 (m, 1 H), 3.11 (s, 3 H), 1.94 (t, J = 6.4 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 161.5, 138.4, 137.3, 129.0, 128.5, 128.3, 127.9, 127.8, 127.1, 93.8, 89.9, 72.2, 63.1, 55.7, 55.4, 53.4. HRMS (FAB): m/z [M + H]+ calcd for C19H22NO4: 328.1549; found: 328.1533.
  • 11 Spectroscopic Data for 7: Colorless crystals; mp 131–133 °C (from MeOH). [α]D 28 –212.9 (c 1.00, CHCl3). IR (film): 3113, 3067, 3031, 2970, 2947, 2847, 1742, 1732, 1601, 1523, 1517, 1351, 1264, 1235, 1105, 1012, 851 cm–1. 1H NMR (400 MHz, CDCl3): δ = 8.13 (d, J = 8.4 Hz, 2 H), 7.62 (d, J = 9.2 Hz, 2 H), 7.42–7.17 (m, 10 H), 6.95 (s, 1 H), 4.95 (d, J = 4.8 Hz, 1 H), 4.48 (d, J = 4.4 Hz, 1 H), 3.72 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 169.5, 162.7, 158.1, 150.6, 137.3, 135.1, 134.2, 130.8, 129.5, 129.1, 129.0, 128.3, 127.7, 126.0, 123.3, 86.7, 71.2, 57.1, 52.9. HRMS (FAB): m/z [M + Na]+ calcd for C25H20N2O7Na: 483.1168; found: 483.1181.
  • 12 For the preparation of N-methylisoxazolinium tetrafluoroborates, see: Cerri A, De Micheli C, Gandolfi R. Synthesis 1974; 710

    • For reduction of isoxazolimium salts, see:
    • 13a Henneböhle M, LeRoy P.-Y, Hein M, Ehrler R, Jäger V. Z. Naturforsch., B: J. Chem. Sci. 2004; 59: 451
    • 13b Jäger V, Frey W, Bathich Y, Shiva S, Ibrahim M, Henneböhle M, LeRoy P.-Y, Imerhasan M. Z. Naturforsch., B: J. Chem. Sci. 2010; 65: 821
    • 14a Barton DH. R, McCombie SW. J. Chem. Soc., Perkin Trans. 1 1975; 1574

    • For reviews, see:
    • 14b Hartwig W. Tetrahedron 1983; 39: 2609
    • 14c Crich D, Quintero L. Chem. Rev. 1989; 89: 1413
  • 15 Spectroscopic Data for 13: [α]D 27 –184.1 (c 0.50, CHCl3); mp 122–124 °C. IR (film) 3362, 3088, 3056, 3030, 2923, 2243, 1670, 1492, 1454, 1401, 1259, 1042, 911, 760 cm–1. 1H NMR (400 MHz, DMSO-d6): δ = 7.28–7.06 (m, 8 H), 6.71–6.69 (m, 2 H), 5.34 (d, J = 3.6 Hz, 1 H), 4.64 (dd, J = 2.8, 3.2 Hz, 1 H), 4.28 (dd, J = 3.2, 5.2 Hz, 1 H), 3.82 (dt, J = 8.4, 12.4 Hz, 1 H), 2.91 (s, 3 H), 2.08–1.96 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 173.4, 141.2, 137.7, 128.4, 127.7, 127.3, 127.0, 126.8, 126.3, 72.1, 67.8, 40.7, 33.1, 30.1. HRMS (FAB): m/z [M + H]+ calcd for C18H20NO2: 282.1494; found: 282.1522.
  • 16 Synthesis of (–)-cis-Clausenamide (2): A mixture of 9 (350 mg, 1.07 mmol) and zinc dust (1.05 g, 16.0 mmol) was heated at 90 °C in AcOH–H2O (10:1, 18 mL) for 3 h. The reaction mixture was concentrated in vacuo, diluted with EtOAc, neutralized with sat. aq NaHCO3 solution and washed with brine. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by silica gel column flash chromatography (CHCl3–MeOH, 15:1) to give (–)-cis-clausenamide (2) (272 mg, 86%). [α]D 26 –6.78 (c 1.00, CHCl3); mp 194–196 °C. IR (film): 3299, 3209, 3181, 2919, 2852, 1684, 1661, 1454, 1404, 1239, 1214, 1103, 1023, 953, 910 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.29–7.19 (m, 10 H), 4.81 (d, J = 4.8 Hz, 1 H), 4.53 (d, J = 6.8 Hz, 1 H), 4.17 (dd, J = 6.0, 0.8 Hz, 1 H), 3.84 (dd, J = 6.0 Hz, 0.8 Hz, 1 H), 3.30 (br. s, 1 H), 2.61 (s, 3 H), 2.23 (br. s, 1 H). 13C NMR (100 MHz, CDCl3): δ = 175.8, 140.6, 134.2, 130.0, 128.6, 128.2, 127.8, 126.7, 71.9, 71.8, 65.8, 47.5, 29.6. HRMS (FAB): m/z [M + H]+ calcd for C18H20NO3: 298.1443; found: 298.1473.