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LETTER
(film): 3113, 3067, 3031, 2970, 2947, 2847, 1742, 1732,
(5) (a) Chen, Y. R.; Yang, M. H.; Huang, L.; Liu, G.; Benz, U.
Ger. Offen. DE3431257 Appl. Aug 24, 1984; Chem. Abstr.
1986, 105, 72689r. (b) 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.
(7) For previous syntheses of these compounds, see:
(a) Hartwig, W.; Born, L. J. Org. Chem. 1987, 52, 4352.
(b) Huang, D. F.; Huang, L. Tetrahedron 1990, 46, 3135.
(c) Yakura, T.; Matsumura, Y.; Ikeda, M. Synlett 1991, 343.
(d) Cappi, M. W.; Chen, W.-P.; Flood, R. W.; Liao, Y.-W.;
Roberts, S. M.; Skidmore, J.; Smith, J. A.; Williamson, N.
M. Chem. Commun. 1998, 1159. (e) Yang, L.; Wang, D.-X.;
Zheng, Q.-Y.; Pan, J.; Huang, Z.-T.; Wang, M.-X. Org.
Biomol. Chem. 2009, 7, 2628. (f) Zhang, L.; Zhou, Y.; Yu,
X. Synlett 2012, 1217. (g) Xuan, Y.-N.; Lin, H.-S.; Yan, M.
Org. Biomol. Chem. 2013, 11, 1815.
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.
(13) For reduction of isoxazolimium salts, see: (a) Henneböhle,
M.; LeRoy, P.-Y.; Hein, M.; Ehrler, R.; Jäger, V. Z.
Naturforsch., B: J. Chem. Sci. 2004, 59, 451. (b) 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.
(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, A. L.; Luche, J.-L.
J. Am. Chem. Soc. 1981, 103, 5454.
(14) (a) Barton, D. H. R.; McCombie, S. W. J. Chem. Soc.,
Perkin Trans. 1 1975, 1574. For reviews, see: (b) Hartwig,
W. Tetrahedron 1983, 39, 2609. (c) Crich, D.; Quintero, L.
Chem. Rev. 1989, 89, 1413.
(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].
(15) Spectroscopic Data for 13: [α]D27 –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]D26 –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.
Major Cycloadduct 5c: [α]D27 –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]D28 –212.9 (c 1.00, CHCl3). IR
Synlett 2014, 25, 2953–2956
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