Efficient and general preparation of pyranostilbenes: First total synthesis of artocarbene and pawhuskin B

Article abstract of DOI:10.1055/s-0029-1216842

An efficient and general synthesis providing pyranostilbenes in moderate yields has been developed. It consists of the reaction of pinosylvin with the appropriate a,β-unsaturated aldehyde catalyzed by ethylenediamine diacetate. As an application of this m

Full text of DOI:10.1055/s-0029-1216842

2146
PAPER
Efficient and General Preparation of Pyranostilbenes: First Total Synthesis of
Artocarbene and Pawhuskin B
Total
Synthesis
o
y
f
A
rtocarben
u
e
and Pawhu
n
skin
B
g Ho Park,a Yong Rok Lee,*a Won Seok Lyoob
a
School of Chemical Engineering and Technology, Yeungnam University, Gyeongsan 712-749, Korea
School of Textiles, Yeungnam University, Gyeongsan 712-749, Korea
b
Received 14 January 2009; revised 10 March 2009
Pawhuskin B (2; Figure 1) was isolated from Dalea pur-
purea, which was used by Plains Indians to ward off dis-
ease and for unspecified ailments together pawhuskins A
and C.19 It has a high affinity for the opioid receptor in
Abstract: An efficient and general synthesis providing pyranostil-
benes in moderate yields has been developed. It consists of the re-
action of pinosylvin with the appropriate a,b-unsaturated aldehyde
catalyzed by ethylenediamine diacetate. As an application of this
methodology, biologically active natural products artocarbene and bioassay testing.19 Recently, a synthetic approach for nat-
pawhuskin B were synthesized by a convergent sequence from
ural pawhuskin C without a benzopyran ring has been re-
ported.20 Natural compounds 3–5 (Figure 1) were isolated
commercially available aldehydes.
Key words: heterocycles,
pawhuskin B
alkenes,
phenols,
artocarbene,
from the roots of Lonchocarpus utilus, used as an insecti-
cide and pesticide,21 and have shown potent inhibition of
NADH:ubiquinone oxidoreductase and phorbol ester in-
duced ornithine decarboxylase activities.21 This range of
Compounds containing the benzopyran moiety are widely important biological activities and properties has stimu-
distributed throughout nature,1 possess many biological lated research into the synthesis of molecules with a ben-
activities,2 and are used as versatile intermediates in or- zopyran moiety on the stilbene. The structures of these
ganic and natural product synthesis.3 Molecules bearing natural products 1–5 have been established by spectral
the stilbene moiety are also widely found in nature4 and analysis, but no synthetic approaches for the formation of
have a variety of interesting biological activities and prop- pyranostilbenes have been reported.
erties, including antimicrobial,5 antimalarial,6 antioxi-
Recently, we developed a new and useful methodology
dant,7
antileukemic,8
anti-platelet
aggregative,9
for preparing a variety of benzopyrans using reactions of
resorcinols with a,b-unsaturated aldehydes catalyzed by
ethylenediamine diacetate (EDDA).22 These reactions in-
volve cycloadditions through a 6p-electrocyclization or
anticarcinogenic,10 anti-HIV,11 protein tyrosine kinase in-
hibitory,12 anti-inflammatory,13 antimutagenic,14 antifun-
gal,15 and hepatoprotective16 activities.
In particular, pyranostilbenes with the benzopyran moiety hetero-Diels–Alder reaction22 and provide a rapid route
on the stilbene are also found in nature.17–20 Among these, for the synthesis of benzopyran derivatives with a variety
artocarbene (1; Figure 1) was isolated from the tropical of substituents on the pyranyl ring. As part of an ongoing
evergreen Artocarpus incisus, distributed throughout study of the synthetic efficacy of this methodology, we
Thailand.6,17 This plant has been used in folk medicine for describe herein an efficient and general synthesis of a
the treatment of tapeworm infection6 and has been shown variety of pyranostilbene derivatives through a domino
to possess antimalarial6 and antityrosinase18 activities. aldol-type reaction and 6p-electrocyclization reaction.
OH
OH
OH
HO
HO
O
O
1
2
artocarbene
HO
pawhuskin B
OMe
OMe
OMe
MeO
MeO
OMe
O
HO
O
O
4
3
5
Figure 1 Naturally occurring compounds 1–5 with benzopyran on the stilbene nucleus
SYNTHESIS 2009, No. 13, pp 2146–2154
x
x.
x
x
.
2
0
0
9
Advanced online publication: 25.05.2009
DOI: 10.1055/s-0029-1216842; Art ID: F01809SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Total Synthesis of Artocarbene and Pawhuskin B
2147
OH
OH
CHO
7
OH
EDDA (20 mol%)
p-xylene
reflux
O
6
8
pinosylvin
78%
Scheme 1 Reaction of pinosylvin (6) with 3-methylbut-2-enal (7) in the presence of ethylenediamine diacetate
OH
OH
citral (9)
EDDA (20 mol%)
benzene
reflux
OH
O
6
10
60%
citral (9)
EDDA (20 mol%)
p-xylene
reflux
O
OH
+
O
O
10
11
23%
40%
Scheme 2 Reaction of pinosylvin (6) with citral (9) in the presence of ethylenediamine diacetate
We also report on the first total synthesis of the naturally Additional reactions of pinosylvin (6) with several types
occurring artocarbene (1) and pawhuskin B (2).
of a,b-unsaturated aldehydes 12–16 were carried out in
the presence of ethylenediamine diacetate (20 mol%) in
refluxing benzene or p-xylene (Table 1). Reaction of 6
with crotonaldehyde (12) for 12 hours afforded adduct 17
in 43% yield (entry 1), whereas treatment with trans-cin-
namaldehyde (13) in refluxing benzene for 12 hours af-
forded compound 18 in 79% yield (entry 2). In the case of
trans,trans-farnesal (14), bearing a long chain, the reac-
tion in refluxing benzene for 12 hours produced the de-
sired product 19 in 58% yield (entry 3). With the other
a,b-unsaturated aldehydes 15 and 16, containing cyclo-
hexene rings, the cycloaddition reactions were also suc-
cessful (entries 4 and 5). Thus, the reactions of 6 with
cyclohex-1-ene-1-carboxaldehyde (15) and (–)-perillalde-
hyde (16) in refluxing p-xylene provided the correspond-
ing adducts 20 and 21 in 67 and 79% yields, respectively,
as single compounds (entries 4 and 5). These reactions
provide a rapid route for the synthesis of pyranostilbenes
with a variety of substituents on the 2H-pyranyl rings.
We first investigated the synthesis of pyranostilbene de-
rivatives using pinosylvin (6) as starting material
(Scheme 1). Reaction of 6 with 3-methylbut-2-enal (7) in
the presence of ethylenediamine diacetate (20 mol%) in
refluxing p-xylene for eight hours afforded benzopyran 8
in 78% yield through a domino aldol-type reaction and a
6p-electrocyclization reaction.22a Compound 8 was easily
separated by column chromatography and characterized
by spectroscopic analyses. In the 1H NMR spectrum, two
vinyl protons on the 2H-pyranyl ring were observed at d =
6.60 (d, J = 9.8 Hz, 1 H) and 5.59 (d, J = 9.8 Hz, 1 H).
As shown in Scheme 2, reaction of pinosylvin (6) with
3,7-dimethylocta-2,6-dienal (citral, 9) in refluxing ben-
zene for ten hours afforded the desired product 10 in 60%
yield. It is interesting that when the temperature was
raised to 138 °C for ten hours by the use of p-xylene as
solvent, both product 10 (23%) and tetracycle 11 (40%)
were produced (Scheme 2). The two compounds were
easily separated by column chromatography and charac-
terized by spectroscopic analyses on the basis of data re-
As an application of this methodology, the total syntheses
of naturally occurring artocarbene (1) and pawhuskin B
(2) were attempted. Scheme 3 shows the retrosynthetic
analysis for artocarbene (1) through disconnection. Arto-
carbene (1) can be prepared by a benzopyran-formation
reaction of trans-stilbene 28 with 3-methylbut-2-enal (7)
through the domino aldol-type reaction and 6p-electrocy-
clization reaction described above. Compound 28 can be
readily generated by a Horner–Wadsworth–Emmons re-
action of benzaldehyde 26 and benzylic phosphonate 25.
Aldehyde 26 can be prepared from commercially avail-
able 2,4-dihydroxybenzaldehyde, while phosphonate 25
1
ported in the literature.19,23 The H NMR spectrum of
compound 10 showed the two vinyl protons on the 2H-
pyranyl ring at d = 6.59 (d, J = 9.8 Hz, 1 H) and 5.49 (d,
J = 9.8 Hz, 1 H), whereas the 1H NMR spectrum of com-
pound 11 showed a methine proton of benzylic position at
d = 2.83 as a broad singlet. Further support for the struc-
tural assignment of tetracycle 11 was obtained from its 13C
NMR spectrum, which clearly showed the expected two
quaternary carbons on the two tetrahydropyranyl rings at
d = 83.8 and 74.7.
Synthesis 2009, No. 13, 2146–2154 © Thieme Stuttgart · New York

2148
B. H. Park et al.
PAPER
Table 1 Reactions of Pinosylvin (6) with a,b-Unsaturated Aldehydes 12–16
Entry
1
a,b-Unsaturated aldehyde
Conditions
Product
Yield (%)
43
OH
O
12
benzene, reflux, 12 h 17
benzene, reflux, 12 h 18
benzene, reflux, 12 h 19
p-xylene, reflux, 12 h 20
H
O
O
O
O
O
OH
O
2
3
4
13
79
58
67
H
O
OH
OH
OH
H
14
O
15
H
O
H
5
16
p-xylene, reflux, 12 h 21
79
may be derived from commercially available 3,5-dihy- quence consisting of mesylate formation followed by dis-
droxybenzaldehyde (22).
placement with sodium iodide. Reaction of iodide 24 with
triethyl phosphite in refluxing xylene for five hours af-
forded the desired phosphonate 25 in 97% yield. The
Horner–Wadsworth–Emmons reaction of phosphonate 25
with benzaldehyde 26 in the presence of potassium tert-
butoxide in tetrahydrofuran gave the desired trans-stil-
bene 27 in 71% yield.24 Deprotection of the two meth-
oxymethyl ethers of compound 27 with concentrated
The synthetic approach of artocarbene (1) is shown in
Scheme 4. Protection of aldehyde 22 with chloromethyl
methyl ether under basic conditions provided by N,N-di-
isopropylethylamine, followed by reduction with sodium
borohydride gave the protected benzyl alcohol 23 in 94%
yield (2 steps). Alcohol 23 was then converted into the
corresponding iodide 24 in 83% yield (2 steps) by a se-
OH
OH
O
OH
OTIPS
+
H
O
OH
28
7
1
HO
TIPSO
OMOM
OTIPS
CHO
O
+
P
EtO
OMOM
TIPSO
OEt
26
25
OH
OHC
OH
22
Scheme 3 Retrosynthetic analysis for artocarbene (1)
Synthesis 2009, No. 13, 2146–2154 © Thieme Stuttgart · New York

PAPER
Total Synthesis of Artocarbene and Pawhuskin B
2149
i) MOMCl
DIPEA
CH2Cl2
OMOM
OH
OMOM
i) MsCl
DIPEA
P(OEt)3
CH2Cl2
HO
ii) NaBH4
MeOH
94%
H
xylene
97%
I
ii) NaI
acetone
83%
OMOM
OH
OMOM
23
22
24
O
OTIPS
OMOM
CHO
OMOM
OTIPS
O
P
concd HCl
26
TIPSO
OMOM
MeOH
60%
t-BuOK
THF
71%
EtO
OMOM
27
OEt
25
TIPSO
O
OH
OH
H
TBAF
OTIPS
OTIPS
7
THF
90%
EDDA
p-xylene
87%
OH
O
28
29
TIPSO
TIPSO
OH
OH
O
1
HO
Scheme 4 Total synthesis of artocarbene (1)
TIPSO
CHO
OMOM
OMOM
TIPSO
concd HCl
O
30
TIPSO
OMOM
P
MeOH
68%
t-BuOK
THF
91%
EtO
OMOM
31
OEt
25
TIPSO
OH
OH
TBAF
citral (9)
THF
91%
EDDA
benzene
61%
TIPSO
TIPSO
TIPSO
TIPSO
OH
O
32
33
OH
HO
HO
O
2
Scheme 5 Total synthesis of pawhuskin B (2)
hydrochloric acid in methanol at room temperature for ten yield.24 Deprotection of the two methoxymethyl ethers
hours afforded compound 28 in 60% yield. Reaction of 28 was accomplished with concentrated hydrochloric acid in
with 3-methylbut-2-enal (7) in the presence of ethylenedi- methanol at room temperature for ten hours to afford com-
amine diacetate (20 mol%) in refluxing xylene for eight pound 32 (68%). Treatment of 32 with citral (9) catalyzed
hours gave adduct 29 (87%). Removal of the two silyl by ethylenediamine diacetate (20 mol%) in refluxing ben-
ether groups with tetrabutylammonium fluoride provided zene for 12 hours gave adduct 33 in 61% yield. Removal
artocarbene (1) in 90% yield. The spectroscopic data of of the two silyl ethers with tetrabutylammonium fluoride
synthetic material 1 was in agreement with the reported in tetrahydrofuran at room temperature for five hours gave
data.17
pawhuskin B (2) in 91% yield. The spectroscopic data of
synthetic compound 2 are identical to those of the natural
product reported in the literature.19
Next, the total synthesis of pawhuskin B (2) (Scheme 5)
began with phosphonate 25, prepared as described above.
The Horner–Wadsworth–Emmons reaction of phospho- In conclusion, we have described reactions for the forma-
nate 25 with benzaldehyde 30, prepared from 3,4-dihy- tion of pyranostilbene derivatives starting from pino-
droxybenzaldehyde, provided trans-stilbene 31 in 91% sylvin (6) and a,b-unsaturated aldehydes 12–16 in the
Synthesis 2009, No. 13, 2146–2154 © Thieme Stuttgart · New York

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B. H. Park et al.
PAPER
13C NMR (75 MHz, CDCl3): d = 154.4, 151.4, 138.3, 137.2, 131.7,
128.9, 128.7, 128.2, 128.1, 127.7, 126.5, 124.1, 116.8, 109.2, 107.1,
106.1, 78.4, 41.1, 26.3, 25.7, 22.7, 17.6.
MS (EI, 70 eV): m/z (%) = 346 [M+] (9), 264 (19), 263 (100), 150
(3), 107 (3), 77 (3), 69 (9), 58 (5).
HRMS (EI): m/z [M+] calcd for C24H26O2: 346.1933; found:
346.1936.
presence of ethylenediamine diacetate. As an application
of this new methodology, the first total syntheses of natu-
ral products artocarbene (1) and pawhuskin B (2) were ac-
complished by a convergent sequence. The required
trans-stilbenes 28 and 32, key intermediates in the synthe-
ses of these two natural products, were prepared in a
straightforward manner by Horner–Wadsworth–Emmons
reactions of the corresponding phosphonates synthesized
from commercially available aldehydes.
Compounds 10 and 11
The reaction of 6 (106 mg, 0.5 mmol) with citral (9; 152 mg, 1.0
mmol) in refluxing p-xylene (10 mL) for 10 h afforded compounds
10 and 11.
All experiments were carried out under a N2 atmosphere. Precoated
silica gel plates (Merck, Art. 5554) with a fluorescent indicator
were used for analytical TLC. Flash column chromatography was
performed on silica gel 9385 (Merck). 1H NMR and 13C NMR spec-
tra were recorded on a Bruker Model ARX (300 and 75 MHz, re-
spectively) spectrometer; samples were prepared in CDCl3 or
acetone-d6. IR spectra were recorded on a Jasco FTIR 5300 spectro-
photometer. HRMS and MS spectra were carried out at the Korea
Basic Science Institute.
Yield (10): 40 mg (23%); yield (11): 69 mg (40%).
Compound 11
Oil.
IR (neat): 3026, 2975, 2930, 1610, 1578, 1449, 1424, 1352, 1314,
1130, 1065, 997, 963, 909, 883, 827, 733 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.41 (d, J = 7.8 Hz, 2 H), 7.27 (dd,
J = 7.8, 7.5 Hz, 2 H), 7.15 (d, J = 7.5 Hz, 1 H), 6.94 (s, 2 H), 6.60
(s, 1 H), 6.57 (s, 1 H), 2.83 (br s, 1 H), 2.24–1.98 (m, 2 H), 1.79 (d,
J = 13.2 Hz, 2 H), 1.48 (s, 3 H), 1.41–1.36 (m, 1 H), 1.33 (s, 3 H),
1.25–1.18 (m, 1 H), 0.98 (s, 3 H), 0.74–0.61 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 157.3, 156.9, 137.4, 136.8, 129.2,
128.6, 128.2, 127.3, 126.4, 116.9, 107.8, 107.4, 83.8, 74.7, 46.7,
37.3, 35.2, 29.7, 29.0, 28.3, 23.8, 22.1.
Pyranostilbenes; General Procedure
EDDA (18 mg, 0.1 mmol) was added to a soln of pinosylvin (6; 0.5
mmol) and the appropriate a,b-unsaturated aldehyde (1.0–1.5
mmol) in benzene (10 mL) or p-xylene (10 mL). The mixture was
refluxed for 8–12 h, and the subsequent removal of the solvent left
an oily residue, which was purified by column chromatography (sil-
ica gel) to give the product.
MS (EI, 70 eV): m/z (%) = 346 [M+] (30), 331 (7), 303 (5), 265 (10),
264 (22), 263 (100), 151 (10), 123 (7), 109 (5), 91 (7), 69 (31).
HRMS (EI): m/z [M+] calcd for C24H26O2: 346.1933; found:
346.1929.
(E)-2,2-Dimethyl-7-styryl-2H-chromen-5-ol (8)
The reaction of 6 (106 mg, 0.5 mmol) with 3-methylbut-2-enal (7;
84 mg, 1.0 mmol) in refluxing p-xylene (10 mL) for 8 h afforded
compound 8.
(E)-2-Methyl-7-styryl-2H-chromen-5-ol (17)
The reaction of 6 (106 mg, 0.5 mmol) with crotonaldehyde (12; 105
mg, 1.5 mmol) in refluxing benzene (10 mL) for 12 h afforded com-
pound 17.
Yield: 109 mg (78%); solid; mp 138–140 °C.
IR (KBr): 3372, 2976, 1615, 1566, 1451, 1424, 1360, 1323, 1275,
1248, 1113, 1046, 957, 868, 826, 777 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.45 (d, J = 8.6 Hz, 2 H), 7.32 (dd,
J = 8.6, 8.4 Hz, 2 H), 7.22 (d, J = 8.4 Hz, 1 H), 7.01 (d, J = 16.3 Hz,
1 H), 6.89 (d, J = 16.3 Hz, 1 H), 6.60 (s, 1 H), 6.60 (d, J = 9.8 Hz, 1
H), 6.46 (s, 1 H), 5.59 (d, J = 9.8 Hz, 1 H), 1.42 (s, 6 H).
Yield: 57 mg (43%); solid; mp 92–93 °C.
IR (KBr): 3425, 2969, 2925, 1615, 1569, 1429, 1296, 1105, 1065,
960, 868, 823, 750 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.47 (d, J = 7.8 Hz, 2 H), 7.35 (dd,
J = 7.8, 7.5 Hz, 2 H), 7.27 (d, J = 7.5 Hz, 1 H), 7.03 (d, J = 16.2 Hz,
1 H), 6.92 (d, J = 16.2 Hz, 1 H), 6.71 (d, J = 9.8 Hz, 1 H), 6.64 (s, 1
H), 6.48 (d, J = 2.0 Hz, 1 H), 5.66 (dd, J = 9.8, 3.3 Hz, 1 H), 5.05–
4.90 (m, 1 H), 1.47 (d, J = 6.6 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 154.6, 151.4, 138.4, 137.0, 129.0,
128.6, 128.1, 127.7, 126.5, 125.3, 117.9, 109.9, 106.9, 106.4, 71.3,
21.0.
13C NMR (75 MHz, CDCl3): d = 154.1, 151.3, 138.4, 137.1, 129.3,
129.0, 128.6, 128.1, 127.7, 126.5, 116.3, 109.3, 107.3, 106.2, 76.1,
27.8.
MS (EI, 70 eV): m/z (%) = 278 [M+] (17), 277 (3), 265 (2), 264 (20),
263 (100), 155 (2), 132 (4), 91 (4).
HRMS (EI): m/z [M+] calcd for C19H18O2: 278.1307; found:
278.1309.
MS (EI, 70 eV): m/z (%) = 264 [M+] (37), 263 (30), 250 (19), 249
(100), 155 (28), 116 (9), 91 (31), 69 (11), 59 (12).
HRMS (EI): m/z [M+] calcd for C18H16O2: 264.1150; found:
264.1146.
(E)-2-Methyl-2-(4-methylpent-3-enyl)-7-styryl-2H-chromen-5-
ol (10)
The reaction of 6 (106 mg, 0.5 mmol) with citral (9; 152 mg, 1.0
mmol) in refluxing benzene (10 mL) for 10 h afforded compound
10.
(E)-2-Phenyl-7-styryl-2H-chromen-5-ol (18)
The reaction of 6 (106 mg, 0.5 mmol) with trans-cinnamaldehyde
(13; 198 mg, 1.5 mmol) in refluxing benzene (10 mL) for 12 h af-
forded compound 18.
Yield: 104 mg (60%); oil.
IR (neat): 3409, 2970, 2921, 1613, 1567, 1429, 1343, 1263, 1198,
1143, 1083, 1058, 960, 824, 749 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.40 (d, J = 8.6 Hz, 2 H), 7.26 (dd,
J = 8.6, 8.4 Hz, 2 H), 7.18 (d, J = 8.4 Hz, 1 H), 6.96 (d, J = 16.3 Hz,
1 H), 6.83 (d, J = 16.3 Hz, 1 H), 6.59 (d, J = 9.8 Hz, 1 H), 6.55 (s, 1
H), 6.39 (s, 1 H), 5.49 (J = 9.8 Hz, 1 H), 5.10–4.98 (m, 2 H), 2.18–
1.99 (m, 2 H), 1.75–1.63 (m, 2 H), 1.60 (s, 3 H), 1.53 (s, 3 H), 1.34
(s, 3 H).
Yield: 129 mg (79%); solid; mp 55–56 °C.
IR (KBr): 3339, 1615, 1564, 1352, 1202, 1144, 1073, 1019, 949,
822, 764, 704 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.37–7.17 (m, 10 H), 6.90 (d,
J = 16.2 Hz, 1 H), 6.78 (d, J = 16.2 Hz, 1 H), 6.77 (d, J = 9.8 Hz, 1
Synthesis 2009, No. 13, 2146–2154 © Thieme Stuttgart · New York

PAPER
Total Synthesis of Artocarbene and Pawhuskin B
2151
H), 6.54 (s, 1 H), 6.40 (s, 1 H), 5.79 (br s, 1 H), 5.70 (d, J = 9.8 Hz,
1 H), 5.25 (br s, 1 H).
1H NMR (300 MHz, CDCl3): d = 7.46 (d, J = 7.5 Hz, 2 H), 7.35 (dd,
J = 7.5, 7.3 Hz, 2 H), 7.27 (d, J = 7.3 Hz, 1 H), 6.99 (d, J = 16.2 Hz,
1 H), 6.89 (d, J = 16.2 Hz, 1 H), 6.59 (s, 1 H), 6.51 (br s, 1 H), 6.45
(s, 1 H), 5.01 (dd, J = 11.1, 5.1 Hz, 1 H), 4.79 (s, 2 H), 2.55 (d,
J = 14.7 Hz, 1 H), 2.34–2.29 (m, 1 H), 2.21–2.13 (m, 2 H), 1.90–
1.73 (m, 3 H), 1.79 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 154.6, 153.8, 150.7, 148.3, 137.2,
137.1, 135.5, 128.6, 128.4, 128.2, 127.5, 126.5, 110.5, 109.3, 106.7,
105.8, 76.6, 43.1, 39.6, 32.4, 31.7, 20.7.
13C NMR (75 MHz, acetone-d6): d = 154.4, 153.3, 141.3, 138.8,
137.3, 128.7, 128.6, 128.5, 128.4, 128.1, 127.6, 126.9, 126.5, 122.7,
118.5, 109.6, 106.7, 105.5, 76.3.
MS (EI, 70 eV): m/z (%) = 326 [M+] (100), 325 (81), 249 (31), 225
(16), 165 (8), 115 (8), 105 (14), 91 (14), 86 (22), 84 (33), 77 (11),
58 (8).
HRMS (EI): m/z [M+] calcd for C23H18O2: 326.1307; found:
326.1307.
MS (EI, 70 eV): m/z (%) = 344 [M+] (100), 343 (64), 329 (23), 315
(21), 301 (5), 276 (25), 275 (51), 262 (38), 165 (10), 149 (12), 115
(10), 91 (13), 83 (11), 69 (14).
2-[(E)-4,8-Dimethylnona-3,7-dienyl]-2-methyl-7-[(E)-styryl]-
2H-chromen-5-ol (19)
HRMS (EI): m/z [M+] calcd for C24H24O2: 344.1776; found:
The reaction of 6 (106 mg, 0.5 mmol) with trans,trans-farnesal (14;
220 mg, 1.0 mmol) in refluxing benzene (10 mL) for 12 h afforded
compound 19.
344.1778.
3,5-Bis(methoxymethoxy)benzyl Alcohol (23)
Protected Benzaldehyde Intermediate
Yield: 120 mg (58%); oil.
MOMCl (1.761 g, 22.0 mmol) was added to a soln of 22 (1.380 g,
10.0 mmol) and DIPEA (5.160 g, 40.0 mmol) in anhyd CH2Cl2 (30
mL) at r.t. The mixture was stirred at r.t. for 10 h, and then H2O (20
mL) was added. The mixture was extracted with CH2Cl2 (3 × 30
mL) and the combined organic extracts were washed with sat. aq
NH4Cl (30 mL) and H2O (20 mL), dried (MgSO4), and evaporated
in vacuo. Flash chromatography (silica gel, hexane–EtOAc, 5:1) af-
forded the protected benzaldehyde.
IR (neat): 3366, 2967, 1612, 1427, 1329, 1070, 960, 823 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.44 (d, J = 8.1 Hz, 2 H), 7.31 (dd,
J = 8.4, 8.1 Hz, 2 H), 7.22 (d, J = 8.4 Hz, 1 H), 6.99 (d, J = 16.3 Hz,
1 H), 6.86 (d, J = 16.3 Hz, 1 H), 6.63 (d, J = 9.8 Hz, 1 H), 6.59 (s, 1
H), 6.42 (s, 1 H), 5.53 (d, J = 9.8 Hz, 1 H), 5.33 (br s, 1 H), 5.12–
5.03 (m, 2 H), 2.19–1.86 (m, 6 H), 1.80–1.68 (m, 2 H), 1.65 (s, 3 H),
1.56 (s, 6 H), 1.38 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 154.4, 151.4, 138.3, 137.2, 135.3,
131.3, 128.9, 128.7, 128.2, 128.1, 127.6, 126.5, 124.3, 123.9, 116.7,
109.2, 107.1, 106.0, 78.5, 41.1, 39.7, 26.7, 26.3, 25.7, 22.6, 17.7,
16.0.
MS (EI, 70 eV): m/z (%) = 414 [M+] (10), 265 (4), 264 (19), 263
(100), 69 (6).
Yield: 2.215 g (98%); oil.
IR (neat): 2955, 2830, 2732, 1702, 1600, 1465, 1389, 1297, 1214,
1153, 1084, 1033, 927, 856, 726 cm–1.
1H NMR (300 MHz, CDCl3): d = 9.88 (s, 1 H), 7.18 (s, 2 H), 6.94
(s, 1 H), 5.18 (s, 4 H), 3.46 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 191.6, 158.7, 138.4, 111.1, 110.4,
HRMS (EI): m/z [M+] calcd for C29H34O2: 414.2559; found:
414.2563.
90.4, 56.2.
Compound 23
(E)-6-Styryl-2,3,4,4a-tetrahydro-1H-xanthen-8-ol (20)
The reaction of 6 (106 mg, 0.5 mmol) with cyclohex-1-ene-1-car-
boxaldehyde (15; 110 mg, 1.0 mmol) in refluxing p-xylene (10 mL)
for 12 h afforded compound 20.
The protected benzaldehyde (2.054 g, 9.1 mmol) in MeOH (3 mL)
was added dropwise to a suspension of NaBH4 (0.344 g, 9.1 mmol)
in MeOH (20 mL) at 0 °C. The mixture was allowed to stir at r.t. for
3 h and then quenched by addition of H2O (30 mL). The mixture
was acidified with 2 N aq HCl (30 mL) and extracted with EtOAc
(3 × 40 mL). The organic layer was washed with H2O (30 mL) and
brine (30 mL), dried (MgSO4), and concentrated under reduced
pressure. The residue was purified by chromatography (silica gel,
hexane–EtOAc, 1:1); this gave protected alcohol 23.
Yield: 102 mg (67%); oil.
IR (neat): 3397, 2930, 1613, 1570, 1431, 1335, 1182, 1155, 1073,
1012, 959, 819, 752, 693 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.47–7.20 (m, 5 H), 6.97 (d,
J = 16.2 Hz, 1 H), 6.87 (d, J = 16.2 Hz, 1 H), 6.53 (s, 1 H), 6.42 (s,
1 H), 6.34 (s, 1 H), 5.15 (br s, 1 H), 4.93–4.89 (m, 1 H), 2.47 (d,
J = 13.8 Hz, 1 H), 2.25–2.21 (m, 1 H), 1.91–1.70 (m, 3 H), 1.54–
1.30 (m, 3 H).
Yield: 1.992 g (96%); oil.
IR (neat): 3419, 2953, 1604, 1462, 1294, 1149, 1082, 1034, 924,
846, 702 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.67 (s, 2 H), 6.61 (s, 1 H), 5.12
(s, 4 H), 4.57 (s, 2 H), 3.44 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 158.3, 143.5, 107.9, 104.0, 94.3,
65.0, 56.0.
13C NMR (75 MHz, CDCl3): d = 153.9, 150.5, 137.2, 137.1, 136.6,
128.6, 128.4, 128.2, 127.5, 126.5, 110.1, 109.3, 106.4, 105.9, 76.6,
35.0, 33.2, 26.7, 24.3.
MS (EI, 70 eV): m/z (%) = 304 [M+] (94), 303 (85), 276 (28), 275
MS (EI, 70 eV): m/z (%) = 228 [M+] (100), 198 (9), 183 (5), 168
(15), 167 (6), 152 (7), 107 (4).
HRMS (EI): m/z [M+] calcd for C11H16O5: 228.0998; found:
(100), 125 (14), 109 (36), 86 (23), 84 (35), 81 (13), 58 (35).
HRMS (EI): m/z [M+] calcd for C21H20O2: 304.1463; found:
304.1462.
228.1000.
3-[(S)-Isopropenyl]-6-[(E)-styryl]-2,3,4,4a-tetrahydro-1H-xan-
then-8-ol (21)
The reaction of 6 (106 mg, 0.5 mmol) with (–)-perillaldehyde (16;
150 mg, 1.0 mmol) in refluxing p-xylene (10 mL) for 8 h afforded
compound 21.
3,5-Bis(methoxymethoxy)benzyl Iodide (24)
MsCl (0.916 g, 8.0 mmol) was added dropwise to a soln of alcohol
23 (1.789 g, 7.8 mmol) and DIPEA (2.012 g, 15.6 mmol) in CH2Cl2
(30 mL) at 0 °C. The mixture was allowed to stir at r.t. for 10 h and
then quenched by the addition of H2O (30 mL). The reaction mix-
ture was extracted with EtOAc (3 × 40 mL). The combined organic
layer was washed with NH4Cl soln (30 mL), H2O (30 mL), and
Yield: 136 mg (79%); oil.
IR (neat): 3400, 2934, 1614, 1579, 1427, 1331, 1163, 1065, 960,
889, 822, 750 cm–1.
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PAPER
brine (30 mL), dried (MgSO4), and concentrated under reduced
pressure. A mixture of the resulting residue and NaI (3.507, 23.4
mmol) in acetone (50 mL) was stirred for 10 h. The removal of the
solvent under reduced pressure left an oily residue, which was then
purified by column chromatography (silica gel, hexane–EtOAc,
5:1) to give product 24.
HRMS (EI): m/z [M+] calcd for C36H60O6Si2: 644.3928; found:
644.3925.
(E)-3,5-Dihydroxy-2¢,4¢-bis(triisopropylsiloxy)stilbene (28)
Concd HCl (5 drops) was added to a soln of 27 (1.305 g, 2.0 mmol)
in MeOH (10 mL), and the mixture was stirred at r.t. for 10 h. Re-
moval of the solvent under reduced pressure left an oily residue,
which was then diluted with H2O (30 mL). The mixture was extract-
ed with EtOAc (3 × 40 mL). The combined organic layer was
washed with sat. aq NaHCO3 (30 mL), H2O (30 mL), and brine (30
mL), dried (MgSO4), and concentrated under reduced pressure. Re-
moval of the solvent under reduced pressure left an oily residue,
which was purified by column chromatography (silica gel, hexane–
EtOAc, 7:1) to give 28.
Yield: 2.188 g (83%); oil.
IR (neat): 3022, 2935, 1601, 1457, 1364, 1179, 1151, 1024, 967,
867, 808, 744 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.70 (s, 2 H), 6.60 (s, 1 H), 5.12
(s, 4 H), 4.35 (s, 2 H), 3.45 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 158.2, 141.2, 110.0, 104.4, 94.4,
56.0, 5.2.
Yield: 0.668 g (60%); oil.
HRMS–FAB: m/z [M + H]+ calcd for C11H16O4I: 339.0093; found:
339.0091.
IR (neat): 3389, 2948, 2868, 1596, 1511, 1302, 1155, 996, 890, 742
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.41 (d, J = 16.5 H, 1 H), 7.39 (d,
J = 8.4 Hz, 1 H), 6.77 (d, J = 16.5 Hz, 1 H), 6.52 (d, J = 2.0 Hz, 2
H), 6.49 (dd, J = 8.4, 2.0 Hz, 1 H), 6.39 (d, J = 2.0 Hz, 1 H), 6.21
(d, J = 2.0 Hz, 1 H), 1.32–1.16 (m, 6 H), 1.13–1.07 (m, 36 H).
13C NMR (75 MHz, CDCl3): d = 156.8, 156.7, 154.5, 140.1, 126.6,
125.5, 124.6, 121.5, 113.6, 110.8, 105.8, 101.6, 18.0, 17.9, 17.8,
13.2, 12.9, 12.7, 12.6.
Diethyl [3,5-Bis(methoxymethoxy)benzyl]phosphonate (25)
P(OEt)3 (1 mL) was added to a soln of 24 (2.025 g, 6.0 mmol) in p-
xylene (10 mL) at r.t. The mixture was heated at 100 °C for 5 h. The
removal of the solvent under reduced pressure left an oily residue,
which was then purified by column chromatography (silica gel,
hexane–EtOAc, 1:1) to give product 25.
Yield: 2.024 g (97%); oil.
MS (EI, 70 eV): m/z (%) = 556 [M+] (100), 515 (12), 514 (29), 513
(71), 207 (10), 186 (12), 87 (11), 73 (13), 59 (16).
IR (neat): 3457, 2982, 1602, 1464, 1400, 1150, 1029, 965, 857, 792
cm–1.
1H NMR (300 MHz, CDCl3): d = 6.61–6.58 (m, 3 H), 5.10 (m, 4 H),
4.05–3.95 (m, 4 H), 3.42 (s, 6 H), 3.01 (d, JPH = 21.6 Hz, 2 H), 1.26–
1.21 (m, 6 H).
HRMS (EI): m/z [M+] calcd for C32H52O4Si2: 556.3404; found:
556.3403.
13C NMR (75 MHz, CDCl3): d = 158.1, 133.6, 111.1, 103.4, 94.3,
62.1, 55.9, 33.9 (d, JCP = 138.1 Hz), 16.2.
(E)-7-[2,4-Bis(triisopropylsiloxy)styryl]-2,2-dimethyl-2H-
chromen-5-ol (29)
EDDA (5 mg, 0.03 mmol) was added to a soln of stilbene 28 (0.167
g, 0.3 mmol) and 3-methylbut-2-enal (7; 0.051 g, 0.6 mmol) in p-
xylene (10 mL). The mixture was refluxed for 8 h and the solvent
was removed; this left an oily residue, which was purified by col-
umn chromatography (silica gel, hexane–EtOAc, 10:1) to give 29.
MS (EI, 70 eV): m/z (%) = 348 [M+] (100), 318 (28), 317 (22), 316
(94), 315 (27), 287 (42), 271 (25), 232 (24), 229 (20), 160 (21).
HRMS (EI): m/z [M+] calcd for C15H25O7P: 348.1338; found:
348.1335.
Yield: 0.162 g (87%); oil.
(E)-3,5-Bis(methoxymethoxy)-2¢,4¢-bis(triisopropylsiloxy)stil-
bene (27)
IR (neat): 3415, 2949, 2868, 1600, 1497, 1425, 1311, 1250, 1113,
1060, 1003, 890, 772 cm–1.
t-BuOK (0.717 g, 6.4 mmol) was added to a soln of 25 (1.055 g, 3.0
mmol) and aldehyde 26 (1.440 g, 3.2 mmol) in THF (30 mL) at
0 °C, and the mixture was stirred at 0 °C for a further 30 min. The
mixture was quenched by the addition of H2O (30 mL) and extract-
ed with EtOAc (3 × 30 mL). The combined organic layer was
washed with NH4Cl soln (30 mL), H2O (30 mL), and brine (30 mL),
dried (MgSO4), and concentrated under reduced pressure. The re-
moval of the solvent under reduced pressure left an oily residue,
which was purified by column chromatography (silica gel, hexane–
EtOAc, 20:1) to give product 27.
1H NMR (300 MHz, CDCl3): d = 7.39 (d, J = 8.4 H, 1 H), 7.38 (d,
J = 16.5 Hz, 1 H), 6.75 (d, J = 16.5 Hz, 1 H), 6.60 (d, J = 9.8 Hz, 1
H), 6.54 (s, 1 H), 6.49 (dd, J = 8.4, 2.0 Hz, 1 H), 6.42 (s, 1 H), 6.39
(d, J = 2.0 Hz, 1 H), 5.56 (d, J = 9.8 HZ, 1 H), 1.42 (s, 6 H), 1.34–
1.19 (m, 6 H), 1.17–1.08 (m, 36 H).
13C NMR (75 MHz, CDCl3): d = 156.6, 154.5, 154.1, 151.3, 139.6,
128.8, 126.7, 125.8, 124.2, 121.7, 116.4, 113.5, 110.8, 108.7, 107.4,
105.4, 75.9, 27.8, 18.0, 17.8, 17.7, 13.0, 12.7.
MS (EI, 70 eV): m/z (%) = 622 [M+] (100), 608 (17), 607 (33), 579
(20), 407 (19), 254 (11), 155 (27), 91 (29).
HRMS (EI): m/z [M+] calcd for C37H58O4Si2: 622.3874; found:
622.3871.
Yield: 1.465 g (71%); oil.
IR (neat): 2948, 2866, 1595, 1495, 1309, 1182, 1149, 1080, 1035,
986, 889, 840, 760 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.45 (d, J = 16.5 Hz, 1 H), 7.42 (d,
J = 8.4 Hz, 1 H), 6.83 (d, J = 16.5 Hz, 1 H), 6.82 (d, J = 2.0 Hz, 2
H), 6.58 (t, J = 2.0 H z, 1 H), 6.49 (dd, J = 8.4, 2.0 Hz, 1 H), 6.38
(d, J = 2.0 Hz, 1 H), 5.15 (s, 4 H), 3.47 (s, 6 H), 1.33–1.16 (m, 6 H),
1.13–1.03 (m, 36 H).
13C NMR (75 MHz, CDCl3): d = 158.5, 156.7, 154.5, 140.6, 126.4,
125.7, 124.4, 121.5, 113.6, 110.8, 107.5, 103.9, 94.5, 56.0, 18.0,
17.9, 17.7, 13.0, 12.7, 12.0.
Artocarbene (1)
A 1.0 M soln of TBAF in THF (0.6 mL, 0.6 mmol) was added to a
soln of 29 (0.151 g, 0.2 mmol) in THF (10 mL) and the mixture was
stirred at r.t. for 5 h. The mixture was then quenched by the addition
of sat. aq NH4Cl (30 mL) and extracted with EtOAc (3 × 40 mL).
The combined organic layer was washed with H2O (30 mL) and
brine (30 mL), dried (MgSO4), and concentrated under reduced
pressure. Removal of the solvent under reduced pressure left an oily
residue, which was purified by column chromatography (silica gel,
hexane–EtOAc, 2:1) to give 1.
MS (EI, 70 eV): m/z (%) = 644 [M+] (100), 601 (12), 407 (23), 87
(10), 73 (15), 59 (14), 57 (10).
Synthesis 2009, No. 13, 2146–2154 © Thieme Stuttgart · New York

PAPER
Total Synthesis of Artocarbene and Pawhuskin B
2153
Yield: 0.068 g (90%); solid.
MS (EI, 70 eV): m/z (%) = 556 [M+] (100), 356 (21), 158 (13), 157
(85), 129 (14), 116 (10), 115 (87), 101 (13), 87 (41), 75 (15), 73
(410, 59 (56), 58 (45).
HRMS (EI): m/z [M+] calcd for C32H52O4Si2: 556.3404; found:
556.3407.
IR (KBr): 3411, 2977, 1610, 1516, 1456, 1264, 1117, 1060, 971,
837, 773 cm–1.
1H NMR (300 MHz, acetone-d6): d = 8.40 (s, 2 H), 7.39 (d, J = 8.4
Hz, 1 H), 7.33 (d, J = 16.5 Hz, 1 H), 7.32 (s, 1 H), 6.87 (d, J = 16.5
Hz, 1 H), 6.65 (d, J = 9.9 Hz, 1 H), 6.57 (s, 1 H), 6.47 (s, 1 H), 6.43
(d, J = 2.4 Hz, 1 H), 6.38 (dd, J = 8.4, 2.4 Hz, 1 H), 5.59 (d, J = 9.9
Hz, 1 H), 1.37 (s, 6 H).
13C NMR (75 MHz, acetone-d6): d = 160.0, 157.8, 155.8, 154.8,
141.5 129.6, 129.1, 126.8, 125.3, 118.7, 118.0, 110.2, 109.3, 107.3,
107.0 104.4, 77.1, 28.8.
(E)-7-[3,4-Bis(triisopropylsiloxy)styryl]-2-methyl-2-(4-methyl-
pent-3-enyl)-2H-chromen-5-ol (33)
EDDA (4.0 mg) was added to a soln of stilbene 32 (0.223, 0.4
mmol) and citral (9; 0.122 g, 0.8 mmol) in benzene (10 mL). The
reaction mixture was refluxed for 12 h; removal of the solvent left
an oily residue, which was purified by column chromatography (sil-
ica gel, hexane–EtOAc, 20:1) to give 33.
(E)-3,5-Bis(methoxymethoxy)-3¢,4¢-bis(triisopropylsiloxy)stil-
bene (31)
Yield: 0.169 g (61%); oil.
t-BuOK (0.494 g, 4.4 mmol) was added to a soln of 25 (1.392 g, 4.0
mmol) and the benzaldehyde 30 (1.532 g, 4.4 mmol) in THF (10
mL) at 0 °C. The mixture was stirred at 0 °C for 30 min, then
quenched by the addition of H2O (40 mL), and extracted with
EtOAc (3 × 40 mL). The combined organic layer was washed with
aq NH4Cl (30 mL), H2O (30 mL), and brine (30 mL), dried
(MgSO4), and concentrated under reduced pressure. The removal of
the solvent under reduced pressure left an oily residue, which was
purified by column chromatography (silica gel, hexane–EtOAc,
20:1) to give product 31.
IR (neat): 3431, 2947, 2868, 1611, 1512, 1301, 1131, 1082, 999,
899 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.95 (d, J = 2.0 Hz, 1 H), 6.87 (d,
J = 16.2 Hz, 1 H), 6.87 (dd, J = 8.1, 2.0 Hz, 1 H), 6.77 (d, J = 8.1
Hz, 1 H), 6.66 (d, J = 16.2 Hz, 1 H), 6.63 (d, J = 9.9 Hz, 1 H), 6.56
(br s, 1 H), 6.40 (br s, 1 H), 5.52 (d, J = 9.9 Hz, 1 H), 5.11–5.06 (m,
1 H), 2.16–2.10 (m, 2 H), 1.74–1.69 (m, 2 H), 1.65 (s, 3 H), 1.57 (s,
3 H), 1.38 (s, 3 H), 1.33–1.24 (m, 6 H), 1.12–1.08 (m, 36 H).
13C NMR (75 MHz, CDCl3): d = 154.3, 151.3, 147.1, 147.0, 138.8,
131.7, 130.2, 128.9, 127.9, 125.8, 124.1, 119.9, 119.5, 117.9, 116.8,
108.7, 106.9, 105.6, 78.4, 41.2, 26.3, 25.7, 22.8, 18.0, 17.9, 17.6,
13.2.
MS (EI, 70 eV): m/z (%) = 690 [M+] (70), 609 (21), 608 (52), 607
(100), 408 (10), 407 (31), 157 (12), 115 (22), 87 (18), 73 (20), 59
(23).
HRMS (EI): m/z [M+] calcd for C42H66O4Si2: 690.4500; found:
690.4496.
Yield: 2.583 g (91%); oil.
IR (neat): 2948, 2867, 1593, 1511, 1463, 1287, 1223, 1981, 1036,
888, 849 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.97–6.89 (m, 3 H), 6.81–6.79 (m,
3 H), 6.75 (d, J = 8.4 Hz, 1 H), 6.62 (t, J = 2.0 H, 1 H), 5.17 (s, 4 H),
3.48 (s, 6 H), 1.34–1.23 (m, 6 H), 1.13–1.03 (m, 36 H).
13C NMR (75 MHz, CDCl3): d = 158.4, 147.2, 147.1, 140.0, 130.1,
129.5, 126.0, 119.9, 119.6, 118.0, 107.7, 103.7, 94.5, 56.1, 18.0.
17.9, 17.7, 13.2, 12.3.
Pawhuskin B (2)
A 1.0 M soln of TBAF in THF (0.6 mL, 0.6 mmol) was added to a
soln of 33 (0.151 g, 0.2 mmol) in THF (10 mL) and the mixture was
stirred at r.t. for 5 h. The reaction mixture was quenched by the ad-
dition of sat. aq NH4Cl (30 mL) and extracted with EtOAc (3 × 40
mL). The combined organic layer was washed with H2O (30 mL)
and brine (30 mL), dried (MgSO4), and concentrated under reduced
pressure. Removal of the solvent under reduced pressure left an oily
residue, which was purified by column chromatography (silica gel,
hexane–EtOAc, 2:1) to give 2.
MS (EI, 70 eV): m/z (%) = 644 [M+] (12), 487 (12), 252 (19), 251
(100), 207 (7), 180 (7), 179 (50), 165 (11), 157 (7), 131 (7), 75 (11).
HRMS (EI): m/z [M+] calcd for C36H60O6Si2: 644.3928; found:
644.3925.
(E)-3,5-Dihydroxy-3¢,4¢-bis(triisopropylsiloxy)stilbene (32)
Concd HCl (5 drops) was added to a soln of 31 (1.290 mg, 2.0
mmol) in MeOH (10 mL) and the mixture was stirred at r.t. for 10
h. The removal of the solvent under reduced pressure left an oily
residue, which was then diluted with H2O (30 mL). The mixture was
extracted with EtOAc (3 × 40 mL). The combined organic layer
was washed with sat. aq NaHCO3 (30 mL), H2O (30 mL), and brine
(30 mL), dried (MgSO4), and concentrated under reduced pressure.
Removal of the solvent under reduced pressure left an oily residue,
which was then purified by column chromatography (silica gel,
hexane–EtOAc, 4:1) to give 32.
Yield: 0.075 g (91%); oil.
IR (neat): 3387, 2937, 1609, 1518, 1442, 1366, 1273, 1195, 1096,
979, 827, 738 cm–1.
1H NMR (300 MHz, acetone-d6): d = 8.11 (br s, 2 H), 7.07 (d,
J = 2.0 Hz, 1 H), 6.97 (d, J = 16.5 Hz, 1 H), 6.91 (dd, J = 8.2, 2.0
Hz, 1 H), 6.80 (d, J = 8.2 Hz, 1 H), 6.79 (d, J = 16.5 Hz, 1 H), 6.71
(d, J = 9.9 Hz, 1 H), 6.55 (s, 1 H), 6.51 (s, 1 H), 5.59 (d, J = 9.9 Hz,
1 H), 5.14–5.09 (m, 1 H), 2.16–2.03 (m, 2 H), 1.72–1.66 (m, 2 H),
1.63 (s, 3 H), 1.57 (s, 3 H), 1.36 (s, 3 H).
13C NMR (75 MHz, acetone-d6): d = 155.5, 154.2, 146.4, 140.0,
132.1, 130.9, 129.7, 128.2, 126.8, 125.4, 120.3, 118.5, 116.5, 114.1,
109.8, 106.9, 106.5, 78.9, 42.1, 26.8, 26.0, 23.7, 17.9.
Yield: 0.757 g (68%); oil.
IR (neat): 3372, 2946, 2867, 1596, 1512, 1465, 1069, 995, 887, 850,
739 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.96 (d, J = 2.0 Hz, 1 H), 6.90 (d,
J = 8.4 Hz, 1 H), 6.89 (d, J = 16.2 Hz, 1 H), 6.79 (d, J = 8.4 Hz, 1
H), 6.70 (d, J = 16.2 Hz, 1 H), 6.54 (d, J = 2.0 Hz, 2 H), 6.23 (t,
J = 2.0 Hz, 1 H), 1.34–1.23 (m, 6 H), 1.13–1.03 (m, 36 H).
13C NMR (75 MHz, CDCl3): d = 156.5, 147.2, 146.9, 140.5, 129.9,
129.6, 125.5, 119.9, 119.6, 118.0, 106.1, 101.9, 18.0, 17.9, 13.1,
12.9.
Acknowledgment
This work was supported by grant No. RTI04-01-04 from the Re-
gional Technology Innovation Program of the Ministry of Know-
ledge Economy (MKE).
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(5) Ali, M. A.; Kondo, K.; Tsuda, Y. Chem. Pharm. Bull. 1992,
40, 1130.
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Synthesis 2009, No. 13, 2146–2154 © Thieme Stuttgart · New York