Enantioselective total synthesis of chiricanine B

Article abstract of DOI:10.1016/S0957-4166(03)00519-6

First enantioselective total synthesis of chiricanine B 1, a novel naturally occurring 3-hydroxybenzopyran, has been achieved from readily available methyl 3,5-hydroxybenzoate 2. The absolute stereochemistry was established via a Sharpless' asymmetric dih

Full text of DOI:10.1016/S0957-4166(03)00519-6

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 14 (2003) 2355–2360
Enantioselective total synthesis of chiricanine B
Ying Li,* Yang Hu, Zhixiang Xie and Xuesong Chen
State Key Laboratory of Applied Organic Chemistry and Institute of Organic Chemistry, Lanzhou University,
Lanzhou 730000, PR China
Received 4 April 2003; accepted 23 June 2003
Abstract—First enantioselective total synthesis of chiricanine B 1, a novel naturally occurring 3-hydroxybenzopyran, has been
achieved from readily available methyl 3,5-hydroxybenzoate 2. The absolute stereochemistry was established via a Sharpless’
asymmetric dihydroxylation (AD) reaction.
© 2003 Elsevier Ltd. All rights reserved.
1. Introduction
3-hydroxybenzopyrans,12 herein we report the first
enantioselective total synthesis of chiricanine B 1 via a
Sharpless AD reaction (Fig. 1).13
2,2-Dimethyl-2H-benzopyran moiety is present in more
than 4000 compounds including natural products and
designed structures.1 Examining the characteristics of
these compounds reveals their diverse structural proper-
ties, and more importantly, their wide ranging biologi-
cal actions, suggesting that derivatives of this
benzopyran motif may be capable of interacting with a
variety of cellular targets.1 In particular, 3-hydroxyben-
zopyrans constitute an important class of these com-
pounds due to their diverse range of interesting
biological properties including protein kinase related
cytotoxicity, antifungal activity, and antitumor
activity.2–6
Figure 1. Chiricanine B 1.
Chiricanine B 1, a novel stilbene containing the 3-
hydroxy-2,2-dimethylbenzopyran moiety, was isolated
from the root bark of Lonchocarpus chiricanus that is
well known for its insecticidal properties in Panama.7
This stilbene derivative was identified as one of the
substances responsible for the antifungal and larvicidal
activities of the L. chiricanus dichloromethane extract.7
Its structure was resolved on the basis of spectrometric
methods but the absolute stereochemistry was not
determined. The construction of the benzopyran ring
was achieved by Steck in 1971 in the synthesis of
racemic decurcinol.8 Recently syntheses of non-racemic
chiral 3-hydroxybenzopyrans were reported by several
groups who used asymmetric enone epoxidation or
Jacobson’s chromene epoxidation.9–11 In continuation
of our work on the synthesis of naturally occurring
2. Results and discussion
The general strategic plan is summarized in Scheme 1;
we envisioned that the desired chiricanine B 1 could be
synthesized by a Wittig reaction. Next we focused on
the construction of the 3-hydroxy benzopyan ring by
treatment of the epoxide 10 under acidic conditions.
The requisite chiral epoxide could be obtained by the
application of Sharpless’ AD reaction and then epoxi-
dation. Further analysis indicated methyl 3,5-hydroxy-
benzoate 2 should be an ideal material.
The total synthesis of chiricanine B 1 is detailed in
Scheme 2. The monobenzylated material 3 was readily
available by selective extraction from a mixture of the
dibenzylated product and diphenolic starting material
2.14 Then the remaining phenolic hydroxyl group was
protected by a MOM group in 89% yield. After reduc-
* Corresponding author. E-mail: liyl@lzu.edu.cn
0957-4166/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0957-4166(03)00519-6

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Y. Li et al. / Tetrahedron: Asymmetry 14 (2003) 2355–2360
Scheme 1.
tion with LiAlH4, the obtained alcohol 5 was converted
to ether 6 in nearly quantitative yield.
In conclusion, the first enantioselective total synthesis
of chiricanine B 1 (3.5% overall yield in 13 steps), has
been achieved from methyl 3,5-dihydroxybenzoate 3.
The absolute stereochemistry was introduced by
employing Sharpless’ AD reaction. The synthetic route
presented here allows access to the variety of com-
pounds, which contain the chiral 3-hydroxybenzopyran
ring.
Although several groups have reported that Bn and
MOM are ortho-metallation directing groups,15–17
regioselective lithiation at the C-4 position of 6 and
then coupling resulted in poor yield under the condi-
tions described.15 It was felt that TMEDA was indis-
pensable for this reaction and the addition of HMPA
can greatly improve the coupling yield.18 Therefore, 6
was indeed regioselectively lithiated at C-4 position in
THF:TMEDA (8:1/v) at −20°C and coupled with
prenyl bromide in the presence of HMPA at −78°C to
furnish 7 in good yield (70%).
3. Experimental
3.1. General information
Melting points were measured on a Kofler hot stage
apparatus and are uncorrected. 1H and 13C NMR
spectra were recorded on an Avance DRX200 or a
Varian Mercury 300 BB spectrometer in CDCl3 solu-
tion using TMS as the internal reference. IR spectra
were obtained on a Nicolet AVATAR 360FT-IR spec-
trometer. Mass spectra were measured on a VG ZAB-
HS or VG-7070 spectrometer by direct inlet at 70 eV.
High resolution mass spectra were recorded on
APEX™ II, ESI positive. Optical rotations were mea-
sured using sodium D line on a Perkin Elmer 341
polarimeter. The enantiomeric excess values were deter-
mined by chiral stationary phase HPLC analysis
(Dikma Chiralcel OD 10U 250×4.6 M, hexane:2-
propanol=95:5, flow rate=1 ml/min, detected at 254
nm on a Prostar330 detector). TLC monitored all reac-
tions. Purification of products was conducted by flash
column chromatography on silica gel (200–300 mesh)
purchased from Yan Tai Yuan Bo Silica Gel Co.
Treatment of 7 with AD-mix-b in ButOH:H2O (1:1/v)
at 0°C for 36 h provided the desired product 8 in 72%
yield with 97% ee. Diol 8 was converted to 9 by
selective mesylation of the secondary alcohol followed
by treatment of K2CO3 in methanol to effect ring
closure in a simple one-pot procedure.19 The construc-
tion of the 3-hydroxybenzopyran ring was achieved by
selectively cleaving the benzyl group under H2/Pd5%–C
followed by the addition of HCOOH in 61% yield for
these two steps. A fourth protecting group, acetyl, was
introduced to mask the corresponding hydroxy group
to give 11 in 82% yield. The TBDMS group was cleanly
removed and the resultant alcohol 12 was oxidized by
PCC/NaOAc in CH2Cl2 to produce aldehyde 13
uneventfully in 85% yield.
Wittig reaction of 13 in benzene furnished the stilbene
14 in 80% yield, with no cis-isomer being observed.20,21
To explain this almost exclusive trans-selectivity, the
planar transition state proposed by Vedejs can be
adopted.22 A model reaction carried out by treatment
of benzaldehyde with the phosphonium salt under the
same conditions confirmed the trans-selectivity (trans-
stilbene:cis-stilbene=8.5:1.5).
3.2. Methyl 3-benzyloxy-5-methoxymethoxybenzoate 4
A solution of 3 (3.37 g, 13 mmol) in THF (60 ml) was
cooled to 0°C under Ar. Then NaH (60%, 626 mg, 15.6
mmol) was added slowly. After the hydrogen evolution
was over, MOMCl (1.14 ml, 15.6 mmol) was dropped
via syringe and the reaction mixture was allowed to
warm to rt 4 h later, the reaction mixture was quenched
by the slow addition of water (5 ml) and was further
extracted with ether (3×100 ml). The combined organic
layers were washed by brine, dried over MgSO4,
filtered, and concentrated to afford yellowish oil. Flash
chromatography (16:1 petrol ether/ethyl acetate) pro-
Finally, the Ac group and the MOM group were
smoothly removed under base and acid conditions
respectively in the same pot to afford 1 (76% yield).
Spectroscopic data of 1 are identical with those
reported.7 Since the rotation direction of synthetic 1 is
the same as the naturally occurring compound, the
absolute configuration of chiricanine B is established as
S.
1
vided 4 (3.49 g, 89%) as colorless oil. H NMR (200

Y. Li et al. / Tetrahedron: Asymmetry 14 (2003) 2355–2360
2357
Scheme 2. Reagents and conditions: (a) BnBr, K2CO3, acetone, reflux, 3 h, 51%; (b) NaH, MOMCl, THF, 0°C to rt, 4 h, 89%;
(c) AlLiH4, Et2O, 0°C to rt, 4 h, 91%; (d) TBDMSCl, imidazole, DMF, rt, 1 h, 98%; (e) n-BuLi, TMEDA, THF, −20°C to 0°C,
1 h, then HMPA, prenyl bromide, −78 to 0°C, 2 h, 70%; (f) BuOH–H2O (1:1), AD-mix-b, NH2SO2CH3, 0°C, 36 h, 72%; (g) (1)
MsCl, pyridine, CH2Cl2, rt, 12 h; (2) K2CO3, CH3OH, reflux, 4 h, 65% for two steps; (h) (1) Pd 5%–C, H2, EtOAc, rt, 4 h; (2)
HCOOH, EtOAc, rt, overnight, 61% for two steps; (i) pyridine, Ac2O, DMAP(cat.), rt, 4 h, 82%; (j) TBAF, THF, rt, 1 h, 99%;
(k) PCC, NaOAc silica gel, CH2Cl2, rt, 4 h, 85%; (l) n-BuLi, benzene, Ph3P+CH2C6H5Cl−, rt, 3 h, 80%; (m) (1) K2CO3, CH3OH,
rt, overnight; (2) 3N HCl, CH3OH, reflux, 1 h, 76% for two steps.
MHz): 3.47 (s, 3H), 3.90 (s, 3H), 5.08 (s, 2H), 5.18 (s,
2H), 6.86–6.89 (m, 1H), 7.30–7.46 (m, 7H). IR (film):
1722, 1597, 1150, 1025, 767, 698. EIMS, m/z (%): 302
(M+, 19), 271 (11), 135 (13), 91 (100), 45 (66).
(KBr): 3347, 3261, 2919, 1590. EIMS, m/z (%): 274
(M+, 27), 149 (48), 91 (100), 45 (35).
3.4. (3-Benzyloxy-5-methoxymethoxybenzyl) tert-butyl-
dimethyl silyl ether 6
3.3. 3-Benzyloxy-5-methoxymethoxybenzyl alcohol 5
To a solution of 5 (2.50 g, 9.1 mmol) in DMF (3 ml)
was added imidazole (1.24 g, 18.2 mmol) and TBDM-
SCl (1.51 g, 10 mmol) successively at ambient tempera-
ture. After 1 h, the reaction mixture was diluted with
ether (90 ml), washed by water (5 ml) and brine, dried
over MgSO4 and concentrated. Flash chromatography
(32:1 petrol ether/ethyl acetate) afforded 6 (3.46 g, 98%)
To a 0°C slurry of LiAlH4 (595 mg, 15.7 mmol) in
anhydrous ether (60 ml), 4 (3.15 g, 104 mmol) was
added under Ar. The slurry was allowed to warm to
ambient temperature and stirred for 3 h. Then the
reaction was quenched by Et2O:H2O/10:1. The organic
phase was extracted with Et2O (3×100 ml), washed by
water (10 ml) and brine, dried over Na2SO4, concen-
trated. Flash chromatography (2:1 petrol ether/ethyl
acetate) gave 5 (2.59 g, 91%) as a white powder. Mp=
1
as colorless oil. H NMR (200 MHz): 0.10 (s, 6H), 0.93
(s, 9H), 3.48 (s, 3H), 4.69 (s, 2H), 5.05 (s, 2H), 5.15 (s,
2H), 6.58–6.59 (m, 1H), 6.64 (s, 2H), 7.34–7.46 (m, 5H).
IR (film): 2953, 1597, 1456, 1371, 1254, 1147, 961, 838,
778. EIMS, m/z (%): 388 (M+, 1), 331 (42), 301 (36),
269 (10), 225 (14), 91 (100), 45 (20).
1
62–63°C. H NMR (200 MHz, CDCl3, l ppm): 1.80
(br. 1H), 3.38 (s, 3H), 4.53 (s, 2H), 4.96 (s, 2H), 5.08 (s,
2H), 6.53 (s, 1H), 6.58 (s, 2H), 7.23–7.36 (m, 5H). IR

2358
Y. Li et al. / Tetrahedron: Asymmetry 14 (2003) 2355–2360
3.5. (3-Benzyloxy-4-prenyl-5-methoxymethoxybenzyl)
stirred for 12 h at rt. After completion of the reaction,
the volatiles were evaporated and the residue were
dissolved in MeOH (5 ml) and treated with K2CO3 (124
mg, 0.90 mmol) by refluxing for 4 h. The solvent was
removed under vaccuo and the residue was diluted by
Et2O (30 ml), washed by water (2 ml), dried (MgSO4),
and concentrated. The residue was purified by flash
chromatography (8:1 petrol/ethyl acetate), which
afforded 9 (138 mg, 65%) as colorless oil. [h]2D1=−6 (c
tert-butyl-dimethyl silyl ether 7
A solution of BuLi in petrol ether (2.5 M, 3.94 ml, 9.90
mmol) was added dropwise to a stirred solution of 6
(3.20 g, 8.25 mmol) in THF: TMEDA (40 ml:5 ml)
under Ar at −20°C. The reaction mixture was allowed
to stand at −20ꢀ0°C for 1 h. Then the solution was
cooled to −78°C, followed by the addition of HMPA
(0.5 ml) and prenyl bromide (1.14 ml, 9.90 mmol). The
reaction mixture was stirred for another 2 h between
−78°C and 0°C. Finally, water (5 ml) was added and
the product extracted with Et2O. The organic layer was
washed with brine, dried (Na2SO4) and concentrated.
The residue was purified by flash chromatography (99:1
petrol/ethyl acetate), which afforded 7 (3.16 g, 70%) as
1
1.2, CHCl3). H NMR (200 MHz): 0.09 (s, 6H), 0.94 (s,
9H), 1.24 (s, 3H), 1.31 (s, 3H), 2.83 (dd, J=12.8 Hz, 4.2
Hz, 1H), 2.97–3.02 (m, 1H), 3.14 (dd, J=12.8 Hz, 4.2
Hz, 1H), 3.48 (s, 3H), 4.69 (s, 2H), 5.09 (s, 2H), 5.19 (s,
2H), 6.67 (s, 1H), 6.74 (s, 1H), 7.34–7.40 (m, 5H). IR
(film): 3414, 2928, 1590, 1114, 1072. EIMS, m/z (%):
472 (M+, 4), 415 (18), 91 (100), 45 (28). Calcd for
(M+NH4): 490.2983, Found: 490.2995.
1
a yellow oil. H NMR (200 MHz): 0.10 (s, 6H), 0.96 (s,
9H), 1.68 (s, 3H), 1.73 (s, 3H), 3.44 (d, J=7.2 Hz, 2H),
3.50 (s, 3H), 4.78 (s, 2H), 5.10 (s, 2H), 5.21 (s, 2H), 6.67
(s, 1H), 6.73 (s, 1H), 7.34–7.47 (m, 5H). IR (film): 2929,
1589, 1434, 1065, 838. EIMS, m/z (%): 456 (M+, 12) 399
(11) 387 (32) 91 (90) 45 (100). Calcd for (M+H):
457.2769. Found 457.2768.
3.8. (S)-2,2-Dimethyl-3-hydroxy-5-methoxymethoxy-7-
(tert-butyl-dimethyl)silyloxybenzopyan 10
5% Pd/C (100 mg) was suspended in EtOAc (6 ml) and
hydrogen was pumped into the slurry to saturate. Then
the solution of 9 (120 mg, 0.254 mmol) in EtOAc was
charged and the solution was stirred under a hydrogen
atmosphere for another 3 h at rt. After the hydrogen-
lization was over, HCOOH (0.5 ml) was added to
complete the cyclization. 5% Pd/C was filtered through
a short pad of silica gel. EtOAc was evaporated and the
residue was purified by flash chromatography (4:1
petrol/ethyl acetate) to give the desired 10 (73.2 mg,
61%) as colorless oil. [h]2D0=−12 (c 1.1, CHCl3). 1H
NMR (200 MHz): 0.10 (s, 6H), 0.94 (s, 9H), 1.30 (s,
3H), 1.36 (s, 3H), 2.70 (dd, J=17.4 Hz, 5.4 Hz, 1H),
2.92 (dd, J=17.4 Hz, 5.0 Hz, 1H), 3.48 (s, 3H), 3.74–
3.82 (m, 1H), 4.65 (s, 2H), 5.18 (s, 2H), 6.52 (s, 1H),
6.63 (s, 1H). IR (film): 3406, 2927, 1098, 838, 777.
Calcd for (M+H): 383.2248, Found: 383.2255.
3.6. (R)-(3-Benzyloxy-4-(2,3-dihydroxy-3-methylbutyl)-
5-methoxymethoxybenzyl) tert-butyl-dimethyl silyl ether
8
A 50 ml flask, equipped with a magnetic stirrer, was
charged with t-BuOH (5 ml), water (5 ml), and AD-
mix-b (1.4 g). Stirring at rt produced two clear phases.
Methane sulfonamide (104 mg, 1.1 mmol) was added
and the mixture was cooled to 0°C whereupon some of
the dissolved salts precipitated. Olefin 7 (456 mg, 1
mmol) was added at once, and the heterogeneous slurry
was stirred vigorously at 0°C for 36 h. While the
mixture was stirred at 0°C, solid sodium sulfite (1.5 g)
was added and the mixture was allowed to warm to
room temperature and stirred for 30 min. Ethyl acetate
(10 ml) was added to the mixture. After separation of
the layers, the aqueous phase was further extracted with
EtOAc (3×15 ml). The combined organic layers were
washed with 2N KOH (5 ml) thoroughly, dried over
anhydrous MgSO4 and concentrated. This crude
product was purified by flash chromatography (2:1
petrol/ethyl acetate) to afford 8 (353 mg, 72%) as a
colorless oil. [h]2D0=+6 (c 1.1, CHCl3). 97% e.e., ret.
time=7.723 min for the (R)-isomer and 8.701 min for
3.9. (S)-3-Acetyloxy-2,2-dimethyl-5-methoxymethoxy-7-
(tert-butyl-dimethyl)silyloxybenzopyan 11
A solution of 10 (65 mg, 0.170 mmol) in pyridine (0.5
ml) and Ac2O (0.5 ml) was added DMAP(5 mg) and
stirred at ambient temperature for 8 h. Then the reac-
tion mixture was diluted with EtOAc (3×10 ml), washed
by water (1 ml) and brine, dried over Na2SO4, concen-
trated in vacuo. A flash chromatography (8:1 petrol
ether/ethyl acetate) afforded 11 (59 mg, 82%) as a
1
the (S)-isomer. H NMR (200 MHz): 0.10 (s, 6H), 0.94
1
(s, 9H), 1.21 (s, 6H), 2.48 (br., 1H), 2.73 (br., 1H), 2.77
(dd, J=13.8 Hz, 10.4 Hz, 1H), 3.03 (dd, J=13.8 Hz, 2
Hz, 1H), 3.49 (s, 3H), 3.52–3.62 (m, 1H), 4.71 (s, 2H),
5.10 (s, 2H), 5.21 (s, 2H), 6.71 (s, 1H), 6.76 (s, 1H),
7.35–7.41 (m, 5H). IR (film): 3412, 2928, 1588, 1068,
838, 777; EIMS, m/z (%): 490 (M+, 3) 91 (100) 45 (95).
Calcd for (M+NH4): 508.3089. Found: 508.3099.
colorless oil. [h]D20=−9 (c 0.8, CHCl3). H NMR (300
MHz): 0.12 (s, 6H), 0.97 (s, 9H), 1.33 (s, 3H), 1.35 (s,
3H), 2.10 (s, 3H), 2.72 (dd, J=15.8 Hz, 5.2 Hz, 1H),
3.01 (dd, J=15.8 Hz, 5.4 Hz, 1H), 3.49 (s, 3H), 4.68 (s,
2H), 5.05 (t, J=5.2 Hz, 1H), 5.19 (s, 2H), 6.55 (s, 1H),
6.66 (s, 1H). IR (film): 2928, 1739, 1059. EIMS, m/z
(%): 424 (M+, 3), 381 (15), 367 (47), 45 (94).
3.7. (S)-(3-Benzyloxy-4-(2,3-oxy-3-methylbutyl)-5-
methoxymethoxybenzyl) tert-butyl-dimethyl silyl ether 9
3.10. (S)-3-Acetyloxy-2,2-dimethyl-5-methoxymethoxy-
benzopyanyl-7-methanol 12
To a solution of 8 (220 mg, 0.45 mmol) in CH2Cl2 (3
ml), pyridine (0.073 ml, 0.90 mmol) and MsCl (0.052
ml) was added at 0°C. Then the reaction mixture was
A solution of 11 (54 mg, 0.127 mmol) in THF (3 ml)
was added a solution of t-BAF in THF (1 M, 0.19 ml,
0.19 mmol) and the reaction mixture was stirred for 2 h

Y. Li et al. / Tetrahedron: Asymmetry 14 (2003) 2355–2360
2359
at ambient temperature. After the evaporation of the
solvent, the residue was purified by a flash chro-
matography (2:1 petrol/ethyl acetate) to give 12 (39
mg, 99%) as colorless oil. [h]2D0=+5 (c 0.5, CHCl3).
1H NMR (300 MHz): 1.20 (s, 3H), 1.23 (s, 3H), 1.71
(br., 1H), 1.96 (s, 3H), 2.61 (dd, J=17.8 Hz, 5.0 Hz,
1H), 2.89 (dd, J=17.8 Hz, 5.4 Hz, 1H), 3.36 (s, 3H),
4.50 (s, 2H), 4.94 (t, J=5.2 Hz, 1H), 5.09 (s, 2H),
6.46 (s, 1H), 6.56 (s, 1H). IR (film): 3411, 1737, 1587,
1151. EIMS, m/z (%): 310 (M+, 4), 45 (100).
residue was diluted with EtOAc, washed by saturated
NaHCO3, water and brine, dried and concentrated.
The crude product was purified (2:1 petrol/ethyl ace-
tate) to furnish 1 (11 mg, 76%) as a yellow amor-
phous powder. [h]2D0=−12 (c 0.9, CHCl3) [lit.7
1
[h]2D0=−9 (c 0.3, CHCl3). H NMR (300 MHz): 1.33
(s, 3H), 1.39 (s, 3H), 2.73 (dd, J=17.1 Hz, 5.0 Hz,
1H), 2.94 (dd, J=17.1 Hz, 4.8 Hz, 1H), 3.85 (t, J=
5.0 Hz, 1H), 4.86 (br., 1H), 6.54 (s, 1H), 6.65 (s, 1H),
6.94 (d, J=15.9 Hz, 1H), 7.03 (d, J=16.5 Hz, 1H),
7.25 (t, J=7.5 Hz, 1H), 7.35 (t, J=7.2 Hz, 2H), 7.48
(d, J=7.5 Hz, 2H). 13C NMR (75 MHz), l 22.24,
24.48, 26.28, 69.25, 77.20, 105.02, 106.23, 107.99,
126.50, 126.50, 127.64, 128.06, 128.67, 128.76, 128.76,
137.14, 137.26, 153.93, 154.54. IR (film): 3402, 2924,
1070, 745, 632, 517. FAB-MS: 296 (M+, 55), 303 (M+
Li, 20), 319 (M+Na, 10), 225 (40), 202 (58), 76 (44).
Calcd for (M+H): 297.1485. Found: 297.1485.
3.11. (S)-3-Acetyloxy-2,2-dimethyl-5-methoxymethoxy-
benzopyanyl-7-methanal 13
To a 25 ml flask, equipped with a magnetic stirrer,
PCC (45 mg, 0.20 mmol), anhydrous NaOAc (10 mg,
0.11 mmol), silica gel (10 mg) and CH2Cl2 (4 ml)
were added and stirred at ambient temperature. A
solution of 12 (39 mg, 0.126 mmol) in CH2Cl2 (1 ml)
was dropped and the reaction mixture was stirred for
4 h. After filtration, the volatiles were evaporated and
the residue was purified through flash chromatogra-
phy (8:1 petrol/ethyl acetate), which afford the 13 (33
mg, 85%) as a colorless oil. [h]2D0=+21 (c 1.5, CHCl3).
1H NMR (300 MHz): 1.23 (s, 3H), 1.26 (s, 3H), 1.99
(s, 3H), 2.68 (dd, J=18.6 Hz, 4.8 Hz, 1H), 2.96 (dd,
J=18.6 Hz, 5.2 Hz, 1H), 3.40 (s, 3H), 4.96 (t, J=5.0
Hz, 1H), 5.15 (s, 2H), 6.95 (s, 1H), 7.06 (s, 1H), 9.76
(s, 1H). IR (film): 3387, 2924, 1738, 1697, 1067.
Calcd for (M+NH4): 326.1598. Found: 326.1599.
Acknowledgements
This work was financially supported by the National
Natural Science Foundation of China (Grant No.
20272020).
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3.12. (S)-3-Acetyloxy-5-methoxymethoxy-2,2-dimethyl-
7-(2-phenylethenyl)benzopyan 14
To the slurry of phosphonium salt (42.7 mg, 0.11
mmol) in benzene (4 ml) flushed with Ar, was added
0.1 ml of n-BuLi in petrol (2.3 M, 0.048 ml, 0.11
mmol). The colored solution was stirred at ambient
temperature for 1 h, after which the solution of 13 in
benzene (1 ml) was dropped via syringe. After stirring
overnight, the reaction was quenched by water (1 ml),
extracted with ether (3×10 ml), washed and concen-
trated. The residue was purified by a flash chro-
matography (32:1 petrol/ethyl acetate) to afford the
desired 14 (32 mg, 80%) as a colorless oil. [h]2D0=−6
(c 0.8, CHCl3). 1H NMR (300 MHz): 1.33 (s, 3H),
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Hz, 1H), 2.96 (dd, J=18.2 Hz, 5.2 Hz, 1H), 3.40 (s,
3H), 5.05 (t, J=5.0 Hz, 1H), 5.24 (s, 2H), 6.74 (s,
1H), 6.82 (s, 1H), 9.76 (s, 1H). IR (film): 3393, 2932,
1737, 1057. Calcd for (M+H): 383.1853. Found:
383.1851.
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