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M.-Y. Kim et al.
LETTER
(13) (a) Jastrzebska, I.; Scaglione, J. B.; DeKoster, G. T.; Rath,
N. P.; Covey, D. F. J. Org. Chem. 2007, 72, 4837.
(b) Fürstner, A.; Thiel, O. R.; Ackermann, L. Org. Lett.
2001, 3, 449. (c) Takahata, H.; Yotsui, Y.; Momose, T.
Tetrahedron 1998, 54, 13505.
(14) (a) Rao, K. S.; Mukkanti, K.; Reddy, D. S.; Pla, M.; Iqbal, J.
Tetrahedron Lett. 2005, 46, 2287. (b) Meta, C. T.; Koide,
K. Org. Lett. 2004, 6, 1785. (c) Zhu, G.; Lu, X.
14: mp 178–179 °C; Rf 0.26 (hexane–EtOAc, 2:1); [a]20
D
+42.6 (c 0.9, CHCl3). 1H NMR (400 MHz, CDCl3): d = 7.38
(dd, J = 15.7, 3.2 Hz, 1 H), 6.81 (m, 4 H), 5.91 (dd, J = 15.6,
1.8 Hz, 1 H), 5.70 (ddt, J = 16.4, 11.4, 5.8 Hz, 1 H), 5.29 (dd,
J = 15.2, 9.2 Hz, 1 H), 4.81–4.91 (m, 1 H), 4.63–4.71 (m, 1
H), 4.10–4.18 (m, 1 H), 3.76 (s, 3 H), 2.25–2.48 (m, 3 H),
2.00 (q, J = 9.3 Hz, 2 H), 1.80–1.91 (m, 2 H), 1.70–1.80 (m,
3 H), 1.63–1.70 (m, 1 H), 1.47–1.55 (m, 1 H), 1.26 (d, J =
6.2 Hz, 3 H), 0.90–1.00 (m, 1 H). 13C NMR (100 MHz,
CDCl3): d = 166.31, 154.02, 151.69, 136.72, 130.67, 117.76,
116.94, 114.81, 78.49, 76.39, 71.89, 55.90, 52.60, 44.50,
40.31, 39.00, 34.33, 31.93, 26.85, 21.01. IR (film, neat):
3496, 2925, 2851, 1709, 1681, 1506, 1443, 1377, 1268,
1227, 1032, 969, 824 cm–1. HRMS: m/z [M]+ calcd for
C23H30O5: 386.2093; found: 386.2090.
4-epi-14: mp 105–106 °C; Rf 0.31 (hexane–EtOAc, 2:1);
[a]20D +40.3 (c 0.65, CHCl3). 1H NMR (400 MHz, CDCl3):
d = 7.10 (dd, J = 15.6, 8.4 Hz, 1 H), 6.81 (s, 4 H), 5.78 (d,
J = 16.0 Hz, 1 H), 5.66 (ddt, J = 14.9, 10.2, 4.6 Hz, 1 H), 5.28
(dd, J = 14.9, 9.6 Hz, 1 H), 4.89–4.99 (m, 1 H), 4.63–4.70
(m, 1 H), 4.42–4.48 (m, 1 H), 3.76 (s, 3 H), 2.86 (q, J = 4.8
Hz, 1 H), 2.18–2.28 (m, 1 H), 2.11–2.18 (m, 1 H), 2.02–2.11
(m, 1 H), 1.92–2.02 (m, 2 H), 1.75–1.87 (m, 2 H), 1.61–1.75
(m, 3 H), 1.48–1.53 (m, 1 H), 1.26 (d, J = 6.4 Hz, 3 H), 0.89–
1.00 (m, 1 H). 13C NMR (100 MHz, CDCl3): d = 166.43,
153.91, 151.97, 151.09, 137.78, 130.17, 119.89, 116.89,
114.80, 79.08, 72.04, 71.91, 55.87, 50.24, 40.33, 39.72,
35.63, 34.58, 32.01, 26.51, 20.93. IR (film, neat): 3475,
2929, 2846, 2364, 1714, 1506, 1457, 1355, 1260, 1228,
1038, 974, 825 cm–1. HRMS: m/z [M]+ calcd for C23H30O5:
386.2093; found: 386.2090.
Synthesis of (+)-Brefeldin A (1): To a solution of 14 (8 mg,
0.02 mmol) in MeCN–H2O (4:1, 0.2 mL) was added CAN
(ceric ammonium nitrate; 22 mg, 0.040 mmol) in MeCN–
H2O (4:1, 0.1 mL) at 0 °C. The reaction mixture was warmed
to r.t. and stirred for 1 h. A solution of sat. aq NH4Cl (2.5
mL) was added. The layers were separated and the aqueous
layer was extracted with EtOAc (2 × 10 mL). The combined
organic layers were dried over MgSO4, filtered, concentrated
in vacuo, and the residue was purified by silica gel chroma-
tography (CH2Cl2–MeOH, 20:1) to give 1 (4.8 mg, 84%) as
a white solid; mp 202–204 °C; Rf 0.23 (CH2Cl2–MeOH,
10:1); [a]22D +86.6 (c 0.9, MeOH). 1H NMR (400 MHz,
CD3OD): d = 7.49 (dd, J = 15.6, 3.0 Hz, 1 H), 5.85 (dd, J =
15.6, 1.9 Hz, 1 H), 5.79 (ddd, J = 15.2, 10.2, 4.7 Hz, 1 H),
5.20 (dd, J = 15.0, 9.6 Hz, 1 H), 4.75–4.83 (m, 1 H), 4.18–
4.25 (m, 1 H), 4.01–4.07 (m, 1 H), 2.39 (q, J = 8.7 Hz, 1 H),
2.12 (ddd, J = 13.6, 8.6, 5.4 Hz, 1 H), 1.96–2.06 (m, 3 H),
1.72–1.92 (m, 6 H), 1.52–1.63 (m, 2 H), 1.40–1.48 (m, 1 H),
1.27 (d, J = 6.3 Hz, 3 H), 0.85–1.00 (m, 1 H). 13C NMR (100
MHz, CD3OD): d = 168.38, 155.12, 138.13, 131.41, 117.78,
76.63, 73.21, 72.98, 53.18, 45.46, 44.09, 41.85, 34.99,
32.97, 28.01, 21.06. IR (film, neat): 3364, 2972, 2927, 2857,
1715, 1442, 1255, 1111, 1077, 1000, 975 cm–1. HRMS: m/z
[M]+ calcd for C16H24O4: 280.1675; found: 280.1681.
Tetrahedron: Asymmetry 1995, 6, 1657.
(15) Rao, K. S.; Mukkanti, K.; Reddy, D. S.; Pal, M.; Iqbal, J.
Tetrahedron Lett. 2005, 46, 2287.
(16) Meta, C. T.; Koide, K. Org. Lett. 2004, 6, 1785.
(17) We were not able to isolate the minor Z-isomers. Only
E-isomers were isolated after column chromatography.
(18) Lewis Acid Mediated Intramolecular Epoxide Opening:
To a solution of 5 (365 mg, 1.14 mmol) in toluene (230 mL)
was added BF3·OEt2 (0.21 mL, 2.3 mmol) at –78 °C for 2 h
using a syringe pump. The reaction mixture was treated with
sat. aq NaHCO3 (20 mL) at –78 °C and the layers were
separated. The aqueous layer was extracted with EtOAc (2 ×
20 mL) and the combined organic layers were dried over
MgSO4, filtered, concentrated in vacuo, and the residue was
purified by silica gel chromatography (hexane–EtOAc, 6:1)
to give 8 and the cis isomer (trans/cis = 88: 12, 203 mg,
72%) as a colorless oil. The ratios were determined by
HPLC.
8: Rf 0.29 (hexane–EtOAc, 3:1); [a]24D –51 (c 0.125, CHCl3).
1H NMR (400 MHz, CDCl3): d = 6.76–6.86 (m, 4 H), 5.78–
5.89 (m, 1 H), 4.94–5.09 (m, 2 H), 4.65–4.72 (m, 1 H), 3.76
(s, 3 H), 3.68–3.75 (m, 1 H), 3.55–3.63 (m, 1 H), 2.26–2.42
(m, 2 H), 2.12–2.22 (m, 1 H), 2.03–2.12 (m, 1 H), 1.69–1.79
(m, 2 H), 1.36 (t, J = 5.5 Hz, 1 H). 13C NMR (100 MHz,
CDCl3): d = 154.06, 152.42, 142.55, 116.70, 114.81, 65.19,
55.88, 46.18, 40.30, 36.33. IR (film, neat): 3447, 3066, 2923,
2353, 1735, 1631, 1584, 1497, 1463, 1436, 1355, 1221,
1177, 1104, 1035, 992, 905, 823, 737 cm–1. HRMS: m/z [M]+
calcd for C15H20O3: 248.1412; found: 248.1417.
cis-Isomer of 8: Rf 0.29 (hexane–EtOAc, 3:1). 1H NMR (400
MHz, CDCl3): d = 6.76–6.86 (m, 4 H), 5.85–5.97 (m, 1 H),
5.04–5.16 (m, 2 H), 4.74–4.81 (m, 1 H), 3.77 (s, 3H), 3.65
(dd, J = 11.2, 7.0 Hz, 1 H), 3.55 (dd, J = 11.2, 6.0 Hz, 1 H),
3.03 (q, J = 4.2 Hz, 1 H), 2.47–2.58 (m, 1 H), 2.00–2.13 (m,
2 H), 1.88–1.97 (m, 1 H), 1.78–1.88 (m, 1 H). 1.40 (t, J = 5.5
Hz, 1 H). 13C NMR (100 MHz, CDCl3): d = 139.13, 116.77,
115.62, 114.82, 78.52, 64.06, 55.08, 43.73, 43.70, 38.39,
35.39.
Macrolactone Synthesis by Ring-Closing Metathesis: A
solution of 2 and 4-epi-2 (32 mg, 0.060 mmol) and 7 (10
mol%) in CH2Cl2 (60 mL) was refluxed at 55 °C for 8 h
under N2. The solvent was removed in vacuo and the residue
was purified by silica gel chromatography (hexane–EtOAc,
30:1) to give the macrocyclic lactones (25 mg, 81%) as a
colorless oil. These lactones (22.6 mg, 0.045 mmol) in THF
(0.5 mL) were treated with 1 M TBAF in THF (2.19 mL,
2.19 mmol) at r.t. for 3 h. The solvent was removed in vacuo
and the residue was purified by silica gel chromatography
(hexane–EtOAc, 5:1) to give 14 (7 mg) and 4-epi-14 (7 mg)
in 78% yield.
Synlett 2009, No. 8, 1303–1306 © Thieme Stuttgart · New York