Facile one-pot transformation of 2,3-epoxy alcohols into allylic alcohols: First total synthesis of (-)-4-O-(6'-hydroxy- 7'(9')-dehydro- 6',7'-dihydrogeranyl)coniferol

Article abstract of DOI:10.1016/S0957-4166(98)00385-1

An efficient and practical synthesis of optically active allylic alcohols from 2,3-epoxy alcohols by the in situ formation of the epoxy iodides and their subsequent reduction with phosphine hydroxyiodide has been established. Using this reaction as the key step, we synthesized (-)-4-O- (6'-hydroxy-7'(9')-dehydro-6',7'-dihydrogeranyl)coniferol.

Full text of DOI:10.1016/S0957-4166(98)00385-1

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 9 (1998) 3755–3762
Facile one-pot transformation of 2,3-epoxy alcohols into allylic
alcohols: first total synthesis of (−)-4-O-(60-hydroxy-
70(90)-dehydro-60,70-dihydrogeranyl)coniferol
Zuosheng Liu, Jiong Lan and Yulin Li ∗
National Laboratory of Applied Organic Chemistry and Institute of Organic Chemistry, Lanzhou University, Lanzhou, 730000,
PR China
Received 6 July 1998; accepted 14 September 1998
Abstract
An efficient and practical synthesis of optically active allylic alcohols from 2,3-epoxy alcohols by the in
situ formation of the epoxy iodides and their subsequent reduction with phosphine hydroxyiodide has been
established. Using this reaction as the key step, we synthesized (−)-4-O-(60-hydroxy-70(90)-dehydro-60,70-
dihydrogeranyl)coniferol. © 1998 Elsevier Science Ltd. All rights reserved.
1. Introduction
Optically active allylic alcohols have been frequently used as chiral building blocks for the preparation
of enantiomerically pure compounds.1 There are at present various methods for the synthesis of optically
active allylic alcohols including the kinetic resolution of racemic allylic alcohols,2 reductive rearrange-
ment of 2,3-epoxy alcohols by metal,3 halide4 and tellurium-based chemistry.5 To our knowledge, one-
pot transformation of 2,3-epoxy alcohols into allylic alcohols, especially via epoxy iodides, is limited to
Dorta’s method4e using a Ph3P, iodine, imidazole, 2,6-lutidine and water system. Dorta’s original method
can be successfully applied to the formation of tertiary allylic alcohols, but gives unsatisfactory results
in the formation of secondary allylic alcohols.
∗
Corresponding author.
0957-4166/98/$ - see front matter © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00385-1

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2. Results and discussion
With a view to efficient synthesis, we have developed a facile approach to the synthesis of chiral allylic
alcohols, starting from the corresponding 2,3-epoxy alcohol, readily available in one step via Sharpless
asymmetric epoxidation6 (Scheme 1).
Scheme 1.
In this scheme, the epoxy alcohol is converted in situ into the corresponding epoxy iodide with
Ph3P, iodide and pyridine, which then undergoes reductive elimination by reaction with phosphine
hydroxyiodide (prepared in situ by addition of H2O7), to give the allylic alcohol. We have examined
this process on a range of substrates (Table 1).
As can be seen from Table 1, the reductive ring opening worked well for trisubstituted 2,3-epoxy
alcohol; the allylic alcohols 1a–4a were obtained in excellent yield and good enantiomeric excess (entries
1–4). Entries 1–2 in the Table 1 illustrated that chirality of the epoxides 1–2 at C-6 is totally conserved
in the allylic alcohols 1a–2a.8 Under the same conditions (entry 5), the 2,3-disubstituted epoxide 5 gave
the rearranged secondary allylic alcohol 5a in 71% yield and 83% ee. In this case, the corresponding
iodohydrin 5b was formed in 28% yield.
To our surprise, 3-phenyloxirane methanol 6 treated under the same conditions (entry 6), gave the
Table 1

Z. Liu et al. / Tetrahedron: Asymmetry 9 (1998) 3755–3762
3757
corresponding iodohydrin 6a in 98% yield. As a consequence of the electronic effect of the phenyl group,
the iodine atom reacted at the C-3 position first.
Some Ligularia species have long been used as folk remedies becasue of their antibiotic, antiphlo-
gistic and antitumor activities.9 Compound 7,10 a novel coniferyl alcohol, was isolated from Ligularia
duciformis (Compoitae). The structure of 7, determined by spectroscopic techniques, corresponded to 4-
O-(60-hydroxy-70(90)-dehydro-60,70-dihydrogeranyl)-coniferol. However, the absolute configuration at
C-60 was not determined. Herein, we report the total synthesis of (60S)-(−)-7 from allylic alcohol 1a
(Scheme 2).
Scheme 2. Reagents and conditions: (a) MOMCl, K2CO3, acetone, reflux, 1 h, 96%; (b) Ph3P_CHCO2CH3, PhH, reflux, 2 h,
96%; (c) 3 N HCl, MeOH, reflux, 30 min, 100%; (d) TBDMSCl, imidazole, DMF, rt, 12 h, 97%; (e) K2CO3, MeOH, rt, 2 h,
100%; (f) Ph3P, NCS, THF, rt, 2 h, 89%; (g) 10, K2CO3, acetone, reflux, 8 h, 82%; (h) LiAlH4, Et2O, 0°C, 12 h, 93%; (i) 1 M
n-Bu4N+F−/THF, rt, 16 h, 97%
Vanillin 8 was protected with MOMCl, then the Wittig reaction gave the unsaturated ester 9. Depro-
tection of the protective group in 9 give the phenol 10.
Compound 1a was protected with TBDMSCl, and then the acetyl group was removed. Alcohol 11 was
converted to the chloride with NCS/Ph3P in dry THF.11 Etherification of chloride was carried out with
10 in K2CO3/acetone at reflux. Ether 12 was reduced by LiAlH4 in Et2O to the corresponding alcohol.
Deprotection of silyl ether with 1 M n-Bu4N+F−/THF at room temperature12 gave the title compound 7
in 97% yield as a white solid (mp 83–84°C), [α]20 −3.93 (c 0.89, CHCl3). The spectral data of the title
D
compound 7 was compatible with the assigned structures.
3. Experimental section
1H NMR spectra were recorded on a Varian FT-80A or a Bruker AM-400 spectrometer and 13C NMR
spectra were recorded on a 100 MHz spectrometer in CDCl3 solution using TMS as the internal reference.
IR spectra were obtained using a FT-170SX (film) spectrophotometer. Mass spectra were measured on a
VG ZAB-HS spectrometer by direct inlet at 70 eV, and signals were given in m/z with relative intensity
(%) in brackets. Optical rotation measurements were carried out on a Perkin–Elmer 141 polarimeter.
All solvents were freshly purified and dried by standard techniques prior to use. All reactions were
routinely carried out under an inert atmosphere of Ar, and monitored by TLC. Purification of products

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Z. Liu et al. / Tetrahedron: Asymmetry 9 (1998) 3755–3762
was conducted by flash column chromatography (FCG) on silica gel (200–300 mesh) purchased from
Qing Dao Marine Chemical Co.
Epoxy alcohols 1, 2 and 5 were prepared according to the literature;6a epoxy alcohol 3 was prepared
from (E)-geranyl acetone by SeO2 oxidation, followed by epoxidation with L-(+)-DET, tert-butyl
hydroperoxide (TBHP) and Ti(OiPr4);6b (ꢀ)-2,3-epoxygeraniol 4 was prepared from the epoxidation
of geraniol with VO(acac)2/TBHP;13 (ꢀ)-2,3-epoxy-3-phenylpropan-1-ol 6 was prepared from the
epoxidation of cinnamyl alcohol with mCPBA.
3.1. General procedure: (2E,6S)-6-hydroxy-7(9)-dehydro-6,7-dihydrogeranyl acetate 1a
To a stirred solution of epoxy alcohol 1 (228 mg, 1 mmol) in dry Et2O:CH3CN (5:3, 8 ml) were added
sequentially Ph3P (786 mg, 3 mmol), pyridine (0.32 ml, 4 mmol) and I2 (381 mg, 1.5 mmol) at 0°C.
After being stirred for 2 h at 0°C, H2O (18 µl, 1 mmol) was added into the system. The reaction mixture
was refluxed for 6 h at 38°C, then 20% Na2S2O3 (aq.) (2 ml) and saturated NaHCO3 (aq.) (2 ml) were
added to quench the reaction and the organic layer was extracted with ether (3×50 ml). The combined
ether extracts were washed with 5% HCl (4×10 ml), saturated NaHCO3 (10 ml), H2O and brine, then
dried. Evaporation of the solvent gave the residue, which was flash chromatographed eluting with pet.
ether:ethyl acetate (v/v 6:1) to afford 1a (194 mg, 91%) as a colorless oil. [α]20 −26.2 (c 0.6, CHCl3);
D
IR (film): νmax=3472, 3074, 2942, 2861, 1727, 1671, 1650, 1296, 1024, 953, 900 cm−1; EIMS (m/z): 213
1
(0.1%, M+1), 185 (0.1), 152 (1.4), 134 (5), 119 (8), 84 (38), 67 (38), 43 (100), 41 (38); H NMR (400
MHz; CDCl3): δ 5.36 (1H, t, J=6.8 Hz, CH_), 4.93, 4.84 (2H, s, CH2_), 4.57 (2H, d, J=7.0 Hz, CH2O),
4.04 (1H, t, J=5.6 Hz, CHO), 2.12–2.02 (2H, m, CH2), 2.04 (3H, s, CH3), 1.75 (3H, s, CH3), 1.72 (3H, s,
CH3), 1.68–1.62 (2H, m, CH2). Anal. calcd for C12H20O3: C, 67.89; H, 9.54. Found: C, 67.76; H, 9.47.
3.2. Preparation and analysis of Mosher’s ester14
To a solution of dicyclohexylcarbodiimide (DCC, 17 mg, 83 µmol) and epoxy alcohol 1a (16 mg, 75
µmol) in 0.5 ml of dry CH2Cl2 was added (S)-(−)-α-methoxy-β-trifluoromethyl-phenylacetic acid (19
mg, 83 µmol) and a catalytic amount of DMAP. After stirring at room temperature for 24 h, the solution
was evaporated in vacuo and the residue was directly chromatographed with pet. ether:ethyl acetate
(15:1). The purified Mosher’s ester (32 mg, 99%) was analyzed by the 400 MHz 1H NMR spectrum.
3.3. (2E,6R)-6-Hydroxy-7(9)-dehydro-6,7-dihydrogeranyl acetate 2a
Epoxy alcohol 2 (650 mg, 2.85 mmol) afforded allylic alcohol 2a (550 mg, 2.59 mmol, 91%) as a
colorless oil. [α]20 +20.8 (c 0.6, CHCl3); 1H NMR (400 MHz; CDCl3): δ 5.37 (1H, t, J=6.7 Hz, CH_),
D
4.94, 4.85 (2H, s, CH2_), 4.58 (2H, d, J=7.0 Hz, CH2O), 4.05 (1H, t, J=6.5 Hz, CHO), 2.17–2.02 (2H,
m, CH2), 2.05 (3H, s, CH3), 1.73 (3H, s, CH3), 1.72 (3H, s, CH3), 1.69–1.62 (2H, m, CH2).
3.4. (5E,9S)-5,10-Dimethyl-9-hydroxy-6,10-undecadienyl-2-one 3a
Epoxy alcohol 3 (404 mg, 1.79 mmol) afforded allylic alcohol 3a (361 mg, 1.72 mmol, 96%) as a
colorless oil. [α]20 −14.4 (c 0.9, CHCl3); IR (film): νmax=3451, 3072, 2959, 2861, 1713, 1649, 898
D
cm−1; EIMS (m/z): 210 (0.2%, M), 192 (0.6, M−18), 177 (2), 159 (3), 134 (7), 119 (8), 93 (7), 82 (2),
67 (13), 55 (10), 43 (100); 1H NMR (400 MHz; CDCl3): δ 5.11 (1H, t, J=7.4 Hz, CH_), 4.92, 4.82 (2H,
s, CH2_), 4.02 (1H, t, J=6.4 Hz, CHO), 2.46 (2H, t, J=7.4 Hz, CH2), 2.28–2.23 (2H, m, CH2), 2.14 (3H,

Z. Liu et al. / Tetrahedron: Asymmetry 9 (1998) 3755–3762
3759
s, CH3), 2.09–1.93 (2H, m, CH2), 1.71 (3H, s, CH3), 1.64 (3H, s, CH3), 1.68–1.55 (2H, m, CH2). Anal.
calcd for C13H22O2: C, 74.24; H, 10.54. Found: C, 74.43; H, 10.48.
3.5. (ꢀ)-Linalool 4a
Epoxy alcohol 4 (340 mg, 2 mmol) afforded linalool 4a (298 mg, 1.94 mmol, 97%) as a colorless oil.
1H NMR (80 MHz; CDCl3): δ 5.91 (1H, dd, J=17.3, 10.7 Hz, CH_), 5.21 (1H, d, J=17.3 Hz, CH_),
5.11 (1H, t, J=6.7 Hz, CH_), 5.07 (1H, d, J=10.7 Hz, CH_), 2.08–1.94 (2H, m, CH2), 1.68 (3H, s, CH3),
1.65 (3H, s, CH3), 1.58–1.50 (2H, m, CH2), 1.28 (3H, s, CH3).
3.6. (3S)-3-Hydroxy-1-tetradecene 5a
Epoxy alcohol 5 (190 mg, 0.83 mmol) afforded allylic alcohol 5a (125 mg, 0.59 mmol, 71%) as a
colorless oil. [α]20 +4.5 (c 0.4, CHCl3); IR (film): νmax=3357, 3008, 2925, 1644, 919 cm−1; EIMS
D
(m/z): 211 (0.6%, M−1), 194 (0.4, M−18), 183 (13), 166 (2), 109 (12), 85 (33), 57 (100); 1H NMR (400
MHz; CDCl3): δ 5.87 (1H, ddd, J=6.4, 10.4, 17.0 Hz, CH_), 5.22 (1H, d, J=17.2 Hz, CH_), 5.10 (1H, d,
J=10.3 Hz, CH_), 4.10 (1H, dt, J=6.34, 6.33 Hz, CHO), 1.55–1.48 (2H, m, CH2), 1.26 (18H, brs, 9CH2),
0.88 (3H, t, J=6.6 Hz, CH3). 5b (108 mg, 0.23 mmol, 28%). IR (film): νmax=3288, 2921, 2851, 1433,
1179, 1100 cm−1; EIMS (m/z): 466 (6%, M), 339 (37), 279 (2), 237 (8), 223 (14), 209 (21), 183 (100),
171 (95), 155 (33), 123 (22), 109 (31), 95 (31), 69 (14), 43 (8); 1H NMR (80 MHz; CDCl3): δ 4.15 (1H,
m, CHI), 3.55 (2H, m, CH2I), 3.34 (1H, m, CHO), 1.55–1.48 (2H, m, CH2), 1.28 (18H, brs, 9CH2), 0.89
(3H, t, J=5.8 Hz, CH3). Anal. calcd for C14H28OI2: C, 36.07; H, 6.05. Found: C, 35.99; H, 6.08.
3.7. 1,3-Diiodo-2-hydroxy-1-phenyl-propane 6a
Epoxy alcohol 6 (150 mg, 1 mmol) afforded iodohydrin 6a (382 mg, 0.98 mmol, 98%) as a yellow
oil. IR (film): νmax=3520, 3059, 3026, 1599, 1490, 1244, 1117, 1067, 1010, 744, 697 cm−1; EIMS (m/z):
388 (0.1%, M), 261 (100, M−127), 253 (2), 183 (8), 133 (18), 105 (36), 91 (51), 77 (18); 1H NMR (80
MHz; CDCl3): δ 7.61–7.28 (5H, m, ArH), 5.26 (1H, t, J=7.8 Hz, CHI), 3.63 (2H, d, J=4.7 Hz, CH2I),
3.18 (1H, dt, J=4.8, 7.9 Hz, CHO), 2.71 (1H, brs, OH). Anal. calcd for C9H10OI2: C, 27.86; H, 2.60.
Found: C, 27.77; H, 2.56.
3.8. Methyl 4-methoxymethoxy-3-methoxy-cinnamate 9
A mixture of vanillin 8 (1.54 g, 10 mmol), methoxymethyl chloride (0.81 ml, 11 mmol) and anhydrous
K2CO3 (3 g) in dry acetone (15 ml) was refluxed for 1 h. The mixture was cooled and filtered. The filtrate
was evaporated and the residue was chromatographed on silica gel with pet. ether:ethyl acetate (15:1) to
give 4-methoxymethoxy-3-methoxy-benzaldehyde (1.90 g, 9.6 mmol, 96%) as a yellow oil. To a solution
of the aldehyde (1 g, 5.05 mmol) in benzene (20 ml) was added (methoxycarbonylmethylene)triphenyl-
phosphorane (2.02 g, 6 mmol), and the mixture was stirred at 80°C for 2 h. The solvent was removed
under vacuum and then the residue was chromatographed on silica gel (pet. ether:ethyl acetate 15:1) to
give the ester 9 (1.22 g, 4.84 mmol, 96%) as a yellow oil. IR (film): νmax=2977, 1712, 1654, 1598, 1512,
1464, 1257, 1159, 986, 921, 846, 815 cm−1; EIMS (m/z): 252 (M, 10%), 222 (11), 206 (2), 176 (4), 147
(3), 119 (2), 89 (3), 77 (4), 45 (100); 1H NMR (80 MHz; CDCl3): δ (ppm) 7.64 (1H, d, J=15.9 Hz, CH_),
7.12 (2H, m, ArH), 7.08 (1H, d, J=1.6 Hz, ArH), 6.33 (1H, d, J=15.9 Hz, CH_), 5.26 (2H, s, OCH2),
3.91 (3H, s, CH3), 3.80 (3H, s, CH3), 3.51 (3H, s, CH3).

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Z. Liu et al. / Tetrahedron: Asymmetry 9 (1998) 3755–3762
3.9. Methyl 4-hydroxy-3-methoxy-cinnamate 10
To a solution of compound 9 (504 mg, 2 mmol) in methanol (10 ml) was added 3 N aqueous HCl
(2 ml). The mixture was refluxed for 30 min and extracted with Et2O (50 ml). The organic phase was
washed with water, brine and dried over Mg2SO4. After evaporation of the solvent, the residue was
chromatographed on silica gel (pet. ether:ethyl acetate 6:1) to give the phenol 10 (415 mg, 2 mmol,
100%) as a yellow oil. IR (film): νmax=3484, 3058, 3003, 2950, 1728, 1634, 1595, 1516, 1099, 982, 848,
819 cm−1; EIMS (m/z): 208 (M, 100%), 177 (13), 145 (35), 117 (13), 89 (14), 77 (12), 51 (13); 1H NMR
(80 MHz; CDCl3): δ 7.63 (1H, d, J=16.0 Hz, CH_), 7.12 (2H, m, ArH), 6.94 (1H, d, J=1.6 Hz, ArH),
6.30 (1H, d, J=16.0 Hz, CH_), 3.90 (3H, s, CH3), 3.80 (3H, s, CH3).
3.10. (2E,6S)-6-(tert-Butyldimethylsilyloxy)-7(9)-dehydro-6,7-dihydrogreaniol 11
To a solution of alcohol 1a (228 mg, 1.08 mmol) in dry DMF (1 ml) was added imidazole (82.8 mg,
2.69 mmol) and tert-butyldimethylchlorosilane (TBDMSCl, 178.3 mg, 1.18 mmol) at room temperature,
and the mixture was stirred at that temperature for 12 h. The reaction mixture was extracted with Et2O
(3×50 ml), the organic phase was washed with H2O, brine and dried with MgSO4. After evaporation of
the solvent, the residue was chromatographed on silica gel (pet. ether:ethyl acetate, 20:1) to give silyl
ether (341 mg, 1.04 mmol, 97%) as a colorless oil. To a solution of the silyl ether (252 mg, 0.77 mmol)
in MeOH (3 ml) was added K2CO3 (76 mg, 0.55 mmol) and the reaction mixture was stirred at room
temperature for 2 h. After concentration of the MeOH in vacuo, the residue was dissolved in Et2O (50 ml)
and washed with water and brine and dried over MgSO4. After evaporation of the solvent, the residue
was chromatographed on silica gel (pet. ether:ethyl acetate 6:1) to give the alcohol 11 (217 mg, 0.77
mmol, 100%) as a colorless oil. [α]20 −4.94 (c 1.2, CHCl3); IR (film): νmax=3348, 3072, 2952, 2886,
D
1669, 1650, 1259, 1081, 1004, 898, 856 cm−1; EIMS (m/z): 227 (M−1, 1%), 209 (1), 185 (14), 141 (11),
1
135 (11), 107 (39), 93 (65), 75 (100), 73 (50), 57 (19), 55 (28), 43 (29), 41 (32); H NMR (400 MHz;
CDCl3): δ 5.41 (1H, t, J=6.9 Hz, CH_), 4.86, 4.77 (2H, s, CH2_), 4.16 (2H, d, J=7.0 Hz, OCH2), 4.02
(1H, t, J=6.3 Hz, OCH), 2.06–1.93 (2H, m, CH2), 1.65–1.56 (2H, m, CH2), 1.67 (6H, s, 2CH3), 0.89 (9H,
s, C(CH3)3), 0.04 (3H, s, SiCH3), 0.02 (3H, s, SiCH3). Anal. calcd for C16H32O2Si: C, 67.55; H, 11.34.
Found: C, 67.73; H, 11.27.
3.11. Methyl (20E,60S)-4-O-[60-(tert-butyldimethylsilyloxy)-70 (90)-dehydro-60,70-dihydrogeranyl]-coni-
ferate 12
A solution of NCS (117 mg, 0.88 mg) and Ph3P (231 mg, 0.88 mmol) in anhydrous THF (1 ml) were
stirred at room temperature for 30 min. A solution of alcohol 11 (216 mg, 0.76 mmol) in THF (2 ml)
was then added dropwise. The reaction mixture was stirred at room temperature for 2 h. The mixture
was extracted with Et2O (50 ml). The organic phase was washed with saturated NaHCO3, water and
brine, then dried. The solvent was evaporated and the residue was chromatographed on silica gel (pet.
ether:ethyl acetate 15:1) to give the chloride (206 mg, 0.68 mmol, 89%) as a colorless oil. To a mixture of
the chloride (206 mg, 0.68 mmol) and phenol 10 (155 mg, 0.75 mmol) in dry acetone (5 ml) was added
anhydrous K2CO3 (138 mg, 1 mmol) and the mixture was refluxed for 8 h. The mixture was evaporated
in vacuo and the residue was chromatographed on silica gel (pet. ether:ethyl acetate 10:1) to give the
ester 12 (263 mg, 0.55 mmol, 82%) as a colorless oil. [α]20 −3.19 (c 1.2, CHCl3); IR (film): νmax=3072,
D
2951, 2856, 1718, 1636, 1598, 1511, 1464, 1255, 1164, 983, 838 cm−1; EIMS (m/z): 417 (M−57, 1%),
345 (2), 323 (3), 307 (4), 267 (52), 265 (54), 250 (43), 219 (12), 208 (100), 185 (18), 135 (10), 107 (12),

Z. Liu et al. / Tetrahedron: Asymmetry 9 (1998) 3755–3762
3761
1
93 (20), 75 (8), 73 (9). H NMR (400 MHz; CDCl3): δ 7.64 (1H, d, J=16.0 Hz, CH_), 7.08 (1H, dd,
J=8.2, 1.7 Hz, ArH), 7.05 (1H, d, J=1.7 Hz, ArH), 6.86 (1H, d, J=8.2 Hz, ArH), 6.32 (1H, d, J=16.0 Hz,
CH_), 5.51 (1H, t, J=6.4 Hz, CH_), 4.76, 4.84 (2H, brs, CH2_), 4.65 (2H, d, J=6.4 Hz, OCH2), 4.01
(1H, t, J=6.2 Hz, OCH), 3.90 (3H, s, OCH3), 3.60 (3H, s, OCH3), 1.97–2.09 (2H, m, CH2), 1.55–1.65
(2H, m, CH2), 1.74 (3H, s, CH3), 1.67 (3H, s, CH3), 0.88 (9H, s, C(CH3)3), 0.029, 0.021 (6H, s, 2SiCH3).
Anal. calcd for C27H42O5Si: C, 68.31; H, 8.92. Found: C, 68.20; H, 8.95.
3.12. (60S)-4-O-(60-Hydroxy-70(90)-dehydro-60,70-dihydrogeranyl)-coniferol 7
To a solution of LiAlH4 (5 mg, 0.13 mmol) in dry Et2O (5 ml) was added, dropwise, 1 ml of dry Et2O
solution of ester 12 (82 mg, 0.173 mmol) at 0°C, and the mixture was stirred at 0°C for 12 h. MeOH
(0.2 ml) was added to decompose the excess reagent and the reaction mixture was extracted with Et2O
(50 ml). The organic phase was washed with water, followed by brine and then dried over MgSO4. After
evaporation of the solvent, the residue was chromatographed on silica gel (pet. ether:ethyl acetate 6:1)
to give the alcohol (72 mg, 0.161 mmol, 93%) as a colorless oil. To a solution of alcohol (32 mg, 71.7
µmol) was added a 1 M THF solution (0.2 ml) of tetrabutylammonium fluoride (TBAF), and the reaction
mixture was stirred at room temperature for 16 h. The reaction mixture was then extracted with Et2O, and
the organic phase was washed with water, followed by brine, and dried over MgSO4. After evaporation
of the solvent, the residue was chromatographed on silica gel (pet. ether:ethyl acetate 3:1) to give the title
compound (7) (23 mg, 69.2 µmol, 97%) as a white solid, mp 83–84°C. [α]20 −3.93 (c 0.89, CHCl3);
D
IR (film): νmax=3312, 3079, 2940, 2868, 1669, 1651, 1586, 1512, 1452, 1418, 1260, 1198, 1091, 991,
901, 862 cm−1; MS (FAB): 332; EIMS (m/z): 180 (100%), 152 (7), 137 (33), 124 (25), 107 (6), 91 (8),
77 (5), 55 (8). 1H NMR (400 MHz; CDCl3): δ 6.94 (1H, d, J=1.3 Hz, ArH), 6.90 (1H, dd, J=8.2 Hz, 1.3
Hz, ArH), 6.83 (1H, d, J=8.2 Hz, ArH), 6.54 (1H, d, J=15.8 Hz, CH_), 6.24 (1H, dt, J=15.8, 5.8 Hz,
CH_), 5.54 (1H, t, J=6.2 Hz, CH_), 4.92, 4.84 (2H, brs, CH2_), 4.62 (2H, d, J=6.2 Hz, CH2O), 4.30
(2H, d, J=5.8 Hz, CH2O), 4.03 (1H, t, J=5.8 Hz, CHO), 3.88 (3H, s, OCH3), 2.01–2.07 (2H, m, CH2),
1.62–1.69 (2H, m, CH2), 1.74 (3H, s, CH3), 1.72 (3H, s, CH3). 13C NMR (100 MHz; CDCl3): δ 149.50,
148.07, 147.29, 140.38, 131.15, 129.81, 126.48, 119.95, 119.52, 113.14, 111.13, 109.14, 75.39, 65.81,
63.77, 55.60, 35.40, 32.68, 17.51, 16.69. Anal. calcd for C20H28O4: C, 72.26; H, 8.49. Found: C, 72.11;
H, 8.46.
Acknowledgements
This work was financially supported by the National Natural Science Foundation of China (Grant No.
29672015).
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