Total synthesis of two natural phenanthrenes: confusarin and a regioisomer

Article abstract of DOI:10.1016/j.tet.2007.09.052

The title compounds were synthesized by radical cyclization of the corresponding stilbenes intermediates. The latter ones arose from a Wittig reaction in a stereoselective manner (Z isomer is either the only one or the major one). Confusarin (1) was prepared in 13 steps from gallic acid. Its regioisomer (2) was obtained in five steps from syringaldehyde.

Full text of DOI:10.1016/j.tet.2007.09.052

Tetrahedron 63 (2007) 12379–12387
Total synthesis of two natural phenanthrenes: confusarin
and a regioisomer
a,b,
Sylvie Radixa,b, and Roland Barret
*
*
a
´
Universite de Lyon, Lyon F-69003, France
Universite Claude Bernard Lyon 1, ISPB and INSERM U863, IFR62, 8 avenue Rockefeller, Lyon Cedex 08 F-69373, France
b
´
Received 16 July 2007; revised 14 September 2007; accepted 20 September 2007
Available online 26 September 2007
Abstract—The title compounds were synthesized by radical cyclization of the corresponding stilbenes intermediates. The latter ones arose
from a Wittig reaction in a stereoselective manner (Z isomer is either the only one or the major one). Confusarin (1) was prepared in 13 steps
from gallic acid. Its regioisomer (2) was obtained in five steps from syringaldehyde.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
developed by Harrowven et al.,14 to synthesize the target
molecules as shown in the following retrosynthetic scheme
(Scheme 1).
Confusarin (1) and 2,4,8-trimethoxyphenanthrene-3,7-diol
(2) have been isolated from a series of Indian orchids, Eria
Confusa,1a Bulbophyllum gymnopus,1b Catasetum barbatum
Lindl.,1c Bulbophyllum reptans,1d Cymbidium pendulum1e
and Thunia alba.1f Very recently, compound (1) has been
extracted for the first time from the fresh rhizomes of Tamus
communis.1g,h Moreover, phenanthrene (2) has also been
identified from Dendrobium densiflorum used in traditional
Chinese folk medicine,2 and from Eulophia nuda Lindl.,
a terrestrial orchid found in the Central and Southeast Asian
regions.3 The structures of these phenanthrenes have been
unequivocally established from both homonuclear {1H;
1H} and heteronuclear {1H; 13C} 2D NMR correlation stud-
ies.4 Confusarin (1) has been evaluated for its cytotoxicity in
the human leukaemia K562 cells (IC50¼46.5 mg mLꢀ1).5
Moreover, it has been found that 1 had notable antitumour
activity on the mouse HePA and ESC.6 On the other hand,
phenanthrene (2) induced a concentration-dependant inhibi-
tion of the spontaneous contractions of the rat ileum with
potencies comparable or higher to that of papaverine.7 More-
over, these compounds have shown stronger antioxidative
activity than BHA.8 Finally, both of them have been evalu-
ated for their anti-inflammatory activity.1h
R1
R1
R2
R2
H3CO
H3CO
3a,b
Br
OCH3
OCH3
OH
OH
1 : R1 = OH, R2 = OMe
2 : R1 = OMe, R2 = OH
a : R1 = OBn, R2 = OMe
b : R1 = OMe, R2 = OBn
R1
R2
CH2 Br
+
H3CO
CHO
OCH3
Br
OBn
4a,b
5
Scheme 1. Retrosynthetic scheme of 1 and 2.
2. Results and discussion
Among the considerable number of synthetic routes now
available to prepare phenanthrene derivatives,9–13 we
decided to use the efficient radical cyclization methodology
The synthesis started with the preparation of the benzyl
bromide (5), which was used during the Wittig process as a
precursor of the phosphonium derivative for the synthesis of
both stilbenes (3a) and (3b). Compound 5 was prepared in
fourstepsfrom commerciallyavailable2,3-dihydroxybenzal-
dehyde with an overall 65% yield via selective methylation of
the more acidic C2-hydroxy group of the starting material,15
O-benzylation, NaBH4 reduction of the aldehyde and bromi-
nation of the resulting benzylic alcohol (7) (Scheme 2).
Keywords: Total synthesis; Wittig reaction; Radical cyclization; Stilbenes;
Aromatics; Phenanthrenes; 2,4,8-Trimethoxyphenanthrene-3,7-diol; Con-
fusarin.
* Corresponding authors. Tel.: +33 4 78777542; fax: +33 4 78777549
(R.B.); tel.: +33 4 78777253; fax: +33 4 78777549 (S.R.); e-mail ad-
dresses: sylvie.radix@univ-lyon1.fr; barret@rockefeller.univ-lyon1.fr
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.09.052

12380
S. Radix, R. Barret / Tetrahedron 63 (2007) 12379–12387
As described by Ellis and Lenger,16 8 was prepared in a two-
CHO
OH
CHO
CHO
b
a
step sequence from bromo vanillin17 with an overall 52%
yield. The crucial bromination at C-6 position was then
attempted. But, whatever the brominating conditions we used
to obtain the para-bromophenol (9a)18 (either Br2/CH2Cl2
(method A), or NBS/DMF (method B)), the reaction pro-
duced only ‘ortho’ isomer (9b) with a moderate yield
(Scheme 3). The structure of 9b was determined by NMR
analysis including {1H; 13C} HMBC correlation, as shown
in Figure 1. Long-distance coupling constants 3J were mea-
sured between the hydroxy proton (6.50 ppm), C-2
(107.2 ppm) and C-4 (141.4 ppm) on one hand, and H-6
(7.15 ppm) and C-5 (151.9 ppm) on the other hand.
100%
71%
OCH3
OCH3
OH
OH
OBn
94%
6
c
CH2Br
OCH3
CH2OH
OCH3
d
97%
OBn
5
OBn
7
Scheme 2. Reagents and conditions: (a) K2CO3, CH3I, DMF; (b) BnBr,
K2CO3, DMF; (c) NaBH4, i-PrOH; (d) PBr3, CH2Cl2.
At this point, we decided to develop an alternative route to
4a using 3,5-dihydroxybenzaldehyde (10) as an important
intermediate. This compound was prepared according to
an efficient procedure based on the selective methylation
of the 4-hydroxy group of methyl gallate.19 This four-step
sequence was reproduced from commercially available gal-
lic acid and led to methyl 4-methoxy gallate (11) with an
overall 61% yield. The final stages of this synthesis entailed
silylation of both hydroxy groups followed by the reduction
of the resulting ester (12) with lithium aluminium hydride in
anhydrous ether.20 In this last step, it should be noted that it
was necessary to add silica gel during the hydrolysis of the
metal alkoxide to avoid extensive cleavage of tert-butyldi-
methylsilyl (TBS) ethers. Oxidizing the resulting alcohol
with pyridinium dichromate (PDC) in dichloromethane led
to the corresponding aldehyde (13),20,21 whose silicon pro-
tecting groups were removed under acidic conditions pro-
viding 10 with a satisfactory overall 41% yield from gallic
acid (Scheme 4).
The next step was the synthesis of 4a involving the regio-
selective aromatic bromination of the hydroxy benzaldehyde
(8) as shown in Scheme 3.
OH
OH
OH
MeO
MeO
Br
MeO
MeO
MeO
MeO
bromination
2
+
6
CHO
CHO
CHO
Br
9a
8
9b
("ortho" isomer)
56%
Method A (Br2) : 0%
Method B (NBS) : 0%
65%
Scheme 3. Bromination of 8.
6.50 ppm
H
With compound (10) in hand, the synthesis of 4a posed spe-
cial challenges including monobromination of 10 and regio-
selective O-alkylation (O-benzylation or O-methylation) of
the resulting 3,5-dihydroxybenzaldehyde (14). Unfortu-
nately, despite the use of a single equivalent of N-bromosuc-
cinimide (NBS) and a meticulous monitoring of the reaction
by TLC, the bromination of 10 always led to a mixture of the
monobromo derivative (14) and of the dibromo product (15)
in a disappointing 7:3 ratio (Scheme 5). However, 14 and 15
were easily separated by column chromatography on silica
gel. The regioselectivity of O-alkylation was then studied.
H3C
O
δ(C-2) = 107.2 ppm
δ(C-4) = 141.4 ppm
δ(C-5) = 151.9 ppm
Br
O
4
2
5
H
H3C
O
3.91 ppm
H6
O
7.15 ppm
9b
Figure 1. Establishment of the structure of 9b by HMBC NMR sequence.
OAc
OR
OH
OH
AcO
AcO
H3CO
RO
HO
HO
HO
HO
a (100%)
COOH
b (94%)
CO2CH3
c (75%)
d (87%)
CO2CH3
CO2CH3
e (100%)
Methyl gallate
11: R = H
12: R = TBS
OTBS
OH
H3CO
TBSO
H3CO
HO
(81%)
CHO
CHO
10
13
Scheme 4. Reagents and conditions: (a) AcCl, CH3OH; (b) Ac2O, NEt3; (c) K2CO3, CH3I, DMF; (d) K2CO3, CH3OH, H2O; (e) TBSCl, imidazole, DMF; (f)
LiAlH4, Et2O then SiO2; (g) PDC, CH2Cl2; (h) HCl 32%, THF.

S. Radix, R. Barret / Tetrahedron 63 (2007) 12379–12387
12381
OH
Br
5.93 ppm
H3CO
HO
14 (53%)
H
O
CHO
δ (C-3) = 148.8 ppm
δ (C-4) = 146.8 ppm
δ (C-6) = 111.5 ppm
MeO
NBS (1eq.)
DMF, rt, 2h
4
+
6
10
H
3
C
H
OH
O
H
H3CO
HO
Br
Ph
Br
16
O
15 (20%)
5.05 ppm
CHO
Br
Figure 2. Establishment of the structure of 16 by HMBC NMR sequence.
Scheme 5. Bromination of 10.
An O-benzylation reaction was then performed on 14 and led
to a mixture of the 3-benzyloxy derivative (16) (39%) and
dibenzyloxy product (17) (28%) (Scheme 6).
The completion of the confusarin synthesis is summarized
in Scheme 7. First, immediately after its preparation, the
benzyl bromide (5) was directly treated with triphenyl-
phosphine without any further purification. The resulting
phosphonium bromide was then allowed to react with benz-
aldehyde (4a) to provide stilbene (3a). The Wittig reac-
tion22 was totally stereoselective and gave a single
stereoisomer. Harrowven et al. have demonstrated that Z-se-
lectivities of Wittig reaction was notably enhanced by elec-
tron donating substituents in both the aldehyde and ylide
components.23 Literature has also shown that using lithium
methoxide as a base in DMF mainly led to the desired (Z)-
alkene.24,25 Nevertheless, NMR analysis did not allow us to
ensure the double bond configuration of 3a. Thus, in order
to confirm its (Z)-stereochemistry, we chose to subject 3a to
free-radical cyclization conditions to generate the phenan-
threne ring system. The radical reaction was performed
by slow dropwise addition of a degassed-toluene solution
of tributyltin hydride and azobisisobutyronitrile (AIBN)
As mentioned in Figure 2, the HMBC NMR correlation
1
allowed to assign all H and 13C chemical shifts of the re-
gioisomer (16) and unambiguously established that O-alkyl-
ation took place at the C-3 hydroxy group. Since a methoxy
group was necessary at C-3 position, 14 was then converted
to derivative (18) by the action of (i) NaH (1 equiv) and (ii)
MeI (1 equiv) (Scheme 8). Using a diluted solution of 14 in
DMF (0.15 M) and adding iodomethane very slowly with a
syringe pump for at least 7 h improved the yield in 18
(42%), whereas only traces of trimethoxy product (19) were
obtained. Furthermore, the starting material (14), which
did not react during O-methylation, was able to be recycled
after purification by column chromatography. Finally, the
last hydroxy group remaining on benzaldehyde (18) was
benzylated to give 4a (Scheme 6).
OH
OBn
H3CO
BnO
H3CO
BnO
1) NaH (1eq.), DMF, 50 °C, 30mn
+
CHO
2) BnBr (1eq., 0.65M), DMF, 50 °C, 3h
CHO
Br
Br
16 (39%)
17(28%)
OH
H3CO
HO
CHO
Br
OH
14
OCH3
H3CO
H3CO
H3CO
H3CO
1) NaH (1eq.), DMF, 50 °C, 30mn
+
2) MeI (1eq., 0.75M), DMF, 50 °C
addition time = 7h30
CHO
CHO
Br
Br
18 (42%)
19 (traces)
K2CO3, BnBr
88%
DMF, 50 °C, 1h30
OBn
H3CO
H3CO
CHO
Br
4a
Scheme 6. O-alkylation of 14.

12382
S. Radix, R. Barret / Tetrahedron 63 (2007) 12379–12387
OBn
to a degassed-toluene solution of stilbene. As anticipated,
H3CO
H3CO
the desired phenanthrene (20) was obtained with 60% yield
after a 6 h 30 min reflux. Interestingly, the free-radical
cyclization was able to be carried out using a rather con-
centrated mixture (0.08 M). Finally, confusarin (1) was
obtained by double phenolic hydroxy deprotection of 20.
Unexpectedly, this double hydrogenolysis needed a high
H2 pressure (20 bar). The improved conditions provided
85% yield of a white solid whose 1H NMR and mass spec-
tral characteristics were identical to those published for the
natural product (1).1a In addition, the 13C NMR spectral
data were also consistent within a 2% margin of error, lead-
ing us to conclude that synthetic 1 was identical to natural
confusarin.
CH2Br
OCH3
3a
a
(Z : E = 100:0)
Br
74%
OBn
OCH3
5
OBn
60%
b
OH
OH
OBn
H3CO
H3CO
H3CO
H3CO
c
85%
Then, this efficient strategy was used to synthesize phenan-
threne (2). The synthesis of bromo benzaldehyde (4b) has
proved easier than preparation of its regioisomer (4a). Bro-
mination of syringaldehyde26 was followed by O-benzyla-
tion to provide 4b with an overall 77% yield (Scheme 8).
Benzyl bromide (5) and bromo benzaldehyde (4b) were
eventually engaged into the Wittig procedure to give stilbene
(3b) as a mixture of stereoisomers (3:1). The individual
OCH3
OCH3
OBn
20
Confusarin (1)
Scheme 7. Reagents and conditions: (a) PPh3, DMF, then 4a, CH3OLi,
DMF; (b) AIBN, Bu3SnH, toluene; (c) H2 (20 bar), Pd/C, AcOEt.
1
products were isolated but assessing H NMR data did not
allow the assignment of double bond configurations.
OCH3
OCH3
HO
a
HO
86%
Each product was then subjected to free-radical cyclization
conditions (AIBN, Bu3SnH and toluene). It was correctly
anticipated that the major isomer was the Z isomer and
gave the desired dibenzyloxy phenanthrene (21) when the
minor one (E isomer) did not react in these conditions
(Scheme 9). Finally, the double benzyl deprotection of 21 us-
ing improved hydrogenolysis conditions led to a white solid
with a 70% yield. Its 1H NMR, mass and UV spectral char-
acteristics were identical to those published for the natural
product (2).1e In addition, the 13C NMR spectral data were
also in agreement within a 2% margin of error, leading us
to conclude that synthetic 2 was identical to the natural
2,4,8-trimethoxyphenanthrene-3,7-diol.
H3CO
CHO
H3CO
CHO
Br
Syringaldehyde
89%
b
OCH3
BnO
CHO
H3CO
Br
4b
Scheme 8. Reagentsandconditions:(a)Br2, CH2Cl2;(b)K2CO3, BnBr, DMF.
OCH3
BnO
OCH3
BnO
b
H3CO
Br
H3CO
OCH3
H3CO
OBn
OBn
(E)-3b
21
CH2Br
OCH3
a
+
76%
OCH3
OCH3
OBn
BnO
HO
H3CO
5
b
c
H3CO
21
60%
70%
Br
OCH3
OCH3
OBn
(Z)-3b
(Z : E = 3:1)
OH
2
Scheme 9. Reagents and conditions: (a) PPh3, DMF, then 4b, CH3OLi, DMF; (b) AIBN, Bu3SnH, toluene; (c) H2 (20 bar), Pd/C, AcOEt.

S. Radix, R. Barret / Tetrahedron 63 (2007) 12379–12387
12383
3. Conclusion
and evaporated. The crude residue was chromatographed
on silica gel (petroleum ether (PE)/AcOEt: 92:8) to give
the compound (6) (1.66 g, 100%) as a white solid. Mp 71–
73 ꢁC; IR (KBr) nmax (cmꢀ1) 3066, 2981, 2937, 2747,
1683, 1583, 1482, 1455; 1H NMR (CDCl3, 200 MHz)
d 4.04 (s, 3H, OMe), 5.17 (s, 2H, CH2), 7.11 (t, 1H, J
8.1 Hz, H-5), 7.21 (dd, 1H, J 1.8, 8.1 Hz, H-4), 7.36–7.48
(m, 6H, H-6, H-arom), 10.46 (s, 1H, CHO).
A strategy for the total synthesis of two natural poly-
methoxylated phenanthrenes is described. This strategy
was designed to use stilbenic intermediates, which were
able to be entailed in free-radical cyclization to provide
the phenanthrene skeleton. Confusarin (1) was obtained
from gallic acid and benzyl bromide (5) with an overall
3% yield from gallic acid. Its regioisomer (2) was more
rapidly synthesized, with an overall 24% yield from syrin-
galdehyde and 5. Finally, due to the interesting and various
biological activities shown by 1 and 2, we decided to prepare
other phenanthrene analogues for a future structure–biological
activity study.
4.3. [3-(Benzyloxy)-2-methoxyphenyl]methanol (7)
Benzaldehyde (6) (3.85 g, 16 mmol) was refluxed in i-PrOH
(50 mL) in the presence of NaBH4 (0.31 g, 8 mmol) for
1.5 h. The reaction was monitored by TLC until completion.
The solution was cooled to room temperature and quenched
with aqueous HCl (10%). The solution was extracted with
AcOEt. The combined organic phases were washed with
aqueous NaHCO3 (2%) and water, dried (Na2SO4), filtered
and evaporated. The crude residue was chromatographed
on silica gel (PE/AcOEt: 80:20) to give the benzyl alcohol
(7) (3.69 g, 94%) as a white solid. Mp 58–60 ꢁC; IR (KBr)
nmax (cmꢀ1) 3450, 3060, 2930, 2860, 2820, 1580, 1560,
4. Experimental
4.1. General procedures
All air- and moisture-sensitive reactions were carried out un-
der a nitrogen atmosphere. For Wittig reaction, toluene was
degassed by nitrogen flush before use. All melting points
were measured on a Barnstead Electrothermal 9200 appara-
tus and were uncorrected. Ultraviolet spectra (UV) were re-
corded on a Shimadzu UV mini 1240 spectrometer. Infrared
spectra (IR) were recorded using NaCl film or KBr pellets on
a Perkin–Elmer FT-IR SPECTRUM ONE spectrometer. 1H
spectra were recorded with Bruker AC200, Bruker
ALS300 and Bruker DRX300 Fourier transform spectrome-
ters, using an internal deuterium lock, operating at 200 and
300 MHz, respectively. 13C NMR spectra were recorded
with Bruker AC200 and Bruker DRX300 Fourier transform
spectrometers, using an internal deuterium lock, operating at
50 and 75 MHz, respectively. Chemical shifts are reported in
part per million (ppm) relative to residual protons of deuter-
1
1475, 1450; H NMR (CDCl3, 200 MHz) d 2.44 (br s, 1H,
OH), 3.95 (s, 3H, OMe), 4.72 (s, 2H, CH2Ph), 5.14 (s, 2H,
CH2OH), 6.92–7.08 (m, 3H, H-4, H-5, H-6), 7.34–7.50
(m, 5H, H-arom); 13C NMR (CDCl3, 50 MHz) d 61.0
(CH3), 61.6 (CH2), 70.9 (CH2), 114.2 (CH), 121.2 (CH),
124.1 (CH), 127.4 (2ꢂCH-arom), 128.0 (CH-arom), 128.6
(2ꢂCH-arom), 134.8 (C), 137.0 (C), 147.6 (C), 151.6 (C).
4.4. 1-(Benzyloxy)-3-(bromomethyl)-2-methoxybenzene
(5)
Phosphorous tribromide (300 mL, 3.16 mmol) was added
dropwise to a stirred solution of the benzyl alcohol (7)
(1.54 g, 6.3 mmol) in CH2Cl2 (30 mL) and cooled at 0 ꢁC.
After 40 min of vigorous stirring the reaction mixture was
slowly quenched with ice water. The dichloromethane layer
was separated and the aqueous layer was further extracted
with dichloromethane. The combined extracts were washed
twice with water. The organic solution was dried over
Na2SO4 and evaporated to give 1.87 g (yield 97%) of the
benzyl bromide (5) as colourless oil.
1
ated solvents (d¼7.26 ppm for H NMR and d¼77.16 ppm
for 13C NMR for CDCl3). Carbon multiplicity was deter-
mined by DEPT experiments. Low- and high-resolution
mass spectroscopy was recorded with a ThermoQuest FIN-
NIGAN MAT 95 XL apparatus operating at 70 eV. Elemen-
tal analyses were performed by the Service Central
d’Analyses du CNRS, Solaize, France. Product purification
by flash column chromatography was performed using
˚
Merck Kieselgel 60 A (40–63 mm). Analytical thin layer
4.5. General procedures for the bromination of (8)
chromatography (TLC) was carried out using Merck com-
mercial aluminium sheets coated (0.2 mm layer thickness)
with Kieselgel 60 F254, with visualization by ultraviolet.
All commercially available chemicals were used as received.
3-Hydroxy-2-methoxybenzaldehyde,15 bromo vanillin,17
2-bromosyringaldehyde,25 compounds 8,16 methyl triacet-
oxygallate and 11,19 1220 and 1320,21 were prepared accord-
ing to the literature procedures.
4.5.1. Method A. To a solution of the hydroxy benzaldehyde
(8) (0.183 g, 1 mmol) in CH2Cl2 (2 mL) was added dropwise
a solution of Br2 (55 mL, 1 mmol) in CH2Cl2 (0.8 mL) at
0 ꢁC and under nitrogen. After 3 h of stirring at 0 ꢁC, the
reaction mixture was quenched with brine and the aqueous
phase was extracted with dichloromethane. The combined
organic extracts were washed with brine and water, dried
(MgSO4) and evaporated. The crude residue was chromato-
graphed on silica gel (PE/AcOEt: 75:25) to give the com-
pound (9b) (0.146 g, 56%) as a pale yellow solid.
4.2. 3-Benzyloxy-2-methoxybenzaldehyde (6)
Benzyl bromide (1 mL, 8.4 mmol) was added to a mixture of
3-hydroxy-2-methoxybenzaldehyde (1.02 g, 6.7 mmol) and
potassium carbonate (1.39 g, 10.1 mmol) in DMF (50 mL).
The mixture was heated at 50 ꢁC for 1.5 h. After cooling,
it was portioned between toluene and water. The aqueous
phase was extracted with toluene. The combined organic
layers were washed with water, dried over Na2SO4, filtered
4.5.2. Method B. To a solution of the hydroxy benzaldehyde
(8) (1.62 g, 8.9 mmol) in DMF (40 mL) was added dropwise
a solution of NBS (1.74 g, 9.8 mmol) in DMF (40 mL) at
0 ꢁC and under nitrogen. After 2.5 h of stirring at 0 ꢁC, the
reaction mixture was quenched with water and the aqueous
phase was extracted with toluene. The combined organic

12384
S. Radix, R. Barret / Tetrahedron 63 (2007) 12379–12387
extracts were washed with water, dried (Na2SO4) and evap-
orated. The crude residue was chromatographed on silica gel
(PE/AcOEt: 90:10) to give the compound (9b) (1.51 g, 65%)
as a pale yellow solid.
nitrogen. The reaction mixture was heated to 50 ꢁC for
30 min and the colour of the solution changed to black.
Then a solution of benzyl bromide (120 mL, 1 mmol) in
DMF (0.65 M, 2 mL) was added at 50 ꢁC with a syringe
pump for 1 h 30 min. The solution was cooled to room
temperature and acidified with aqueous HCl (10%) to pH
1. Water was added and the aqueous phase was extracted
with AcOEt. The combined organic extracts were washed
with brine to pH 4–5, dried (Na2SO4), filtered and evapo-
rated. The crude residue was chromatographed on silica
gel (PE/AcOEt: 90:10) to give the 3-benzyloxy compound
(16) (0.131 g, 39%) as a pale brown solid and the 3,5-diben-
zyloxy product (17) (0.120 g, 28%) as a white solid.
4.5.3. 2-Bromo-3-hydroxy-4,5-dimethoxybenzaldehyde
(9b). Mp 138–141 ꢁC; IR (KBr) nmax (cmꢀ1) 3379, 3104,
3068, 2954, 2944, 2770, 1675, 1579, 1575, 1489; 1H NMR
(CDCl3, 200 MHz) d 3.91 (s, 3H, C5-OCH3), 4.01 (s, 3H,
C4-OCH3), 6.50 (s, 1H, OH), 7.15 (s, 1H, H-6), 10.28 (s,
1H, CHO); 13C NMR (CDCl3, 75 MHz) d 56.6 (C5-
OCH3), 61.7 (C4-OCH3), 104.9 (CH, C-6), 107.2 (C, C-2),
129.0 (C, C-1), 141.4 (C, C-4), 147.4 (C, C-3), 151.9 (C,
C-5), 191.5 (CH, CHO).
4.8.1. 3-Benzyloxy-2-bromo-5-hydroxy-4-methoxybenz-
aldehyde (16). Mp 138–141 ꢁC; IR (KBr) nmax (cmꢀ1
)
4.6. 3,5-Dihydroxy-4-methoxybenzaldehyde (10)
3306, 3066, 3028, 2946, 2868, 1672, 1596, 1476, 1422,
1399, 1340, 1255, 1163, 1078; 1H NMR (CDCl3,
200 MHz) d 4.05 (s, 3H, OMe), 5.05 (s, 2H, CH2), 5.93 (s,
1H, OH), 7.40–7.46 (m, 4H, H-6, H-arom meta, H-arom
para), 7.53–7.58 (m, 2H, H-arom ortho), 10.30 (s, 1H,
CHO); 13C NMR (CDCl3, 50 MHz) d 61.5 (CH3), 75.9
(CH2), 111.5 (CH, C-6), 114.8 (C, C-2), 128.7 (4*CH,
CH-arom ortho, meta), 128.7 (CH, CH-arom para), 130.0
(C, C-1), 136.4 (C, C-arom ipso), 146.8 (C, C-4), 148.8
(C, C-3), 149.6 (C, C-5), 191.4 (CH, CHO).
Aqueous HCl (32%, 13 mL, 114 mmol) was added to a solu-
tion of bis-silylanoxy benzaldehyde (13) (11.05 g, 28 mmol)
in THF (80 mL). After 16 h of stirring at room temperature,
brine was added and aqueous phase was extracted with
AcOEt. The combined organic extracts were washed with
brine, dried (Na2SO4), filtered and evaporated. The crude
residue was recrystallised from PE/Et2O to give the dihy-
droxybenzaldehyde (10) (3.83 g, 81%) as a violet solid.
Mp 147–148 ꢁC; IR (KBr) nmax (cmꢀ1) 3376, 3065, 2954,
2854, 1684, 1592, 1524, 1465; 1H NMR (CDCl3+1 drop of
DMSO-d6, 300 MHz) d 3.87 (s, 3H, OMe), 6.88 (s, 2H, H-
1, H-2), 8.26 (s, 2H, 2ꢂOH), 9.65 (s, 1H, CHO).
4.8.2. 3,5-Dibenzyloxy-2-bromo-4-methoxybenzaldehyde
(17). Mp 74–76 ꢁC; IR (KBr) nmax (cmꢀ1) 3064, 3033, 2940,
2866, 1683, 1574, 1561, 1480, 1453, 1432, 1418, 1383,
1329, 1284, 1183, 1098; 1H NMR (CDCl3, 200 MHz)
d 4.01 (s, 3H, OMe), 5.11 (s, 2H, CH2Ph), 5.18 (s, 2H,
CH2Ph), 7.36–7.46 (m, 9H, H-6, H-arom), 7.50–7.61 (m,
2H, H-arom), 10.32 (s, 1H, CHO).
4.7. General procedure for the bromination of 10
To a solution of benzaldehyde (10) (1.70 g, 10 mmol) in
DMF (50 mL) was added dropwise a solution of NBS (2.7 g,
15 mmol) in DMF (30 mL) at room temperature and under
nitrogen. After 2 h of stirring, the mixture was quenched
with water and the aqueous phase was extracted with AcOEt.
The combined organic extracts were washed with water,
dried (Na2SO4) and evaporated. The crude residue was
chromatographed on silica gel (PE/AcOEt: 70:30) to give
the product (14) (1.31 g, 53%) as a pale brown solid and
the dibromo derivative (15) (0.649 g, 20%) as a white solid.
4.9. 2-Bromo-5-hydroxy-3,4-dimethoxybenzaldehyde
(18)
NaH (50%, dispersion in mineral oil, 0.55 g, 11.5 mmol)
was added to a solution of benzaldehyde (14) (2.83 g,
11.4 mmol) in DMF (0.1 M, 100 mL) at room temperature
under nitrogen. The reaction mixture was heated to 50 ꢁC
for 30 min and the colour of the solution changed to black.
Then a solution of methyl iodide (710 mL, 11.4 mmol) in
DMF (0.76 M, 15 mL) was added at 50 ꢁC with a syringe
pump for 7 h 30 min. The solution was cooled to room
temperature and acidified with aqueous HCl (10%) to pH
1. Water was added and the aqueous phase was extracted
with AcOEt. The combined organic extracts were washed
with brine to pH 4–5, dried (Na2SO4), filtered and evapo-
rated. The crude residue was chromatographed on silica
gel (PE/AcOEt: 90:10) to give the compound (18) (1.24 g,
4.7.1. 2-Bromo-3,5-dihydroxy-4-methoxybenzaldedyde
(14). Mp 161–164 ꢁC (decomp.); IR (KBr) nmax (cmꢀ1
)
3433, 3275, 3004, 2956, 1682, 1582, 1498, 1461, 1438; 1H
NMR (CDCl3+1 drop of DMSO-d6, 200 MHz) d 3.96 (s,
3H, OMe), 7.11 (s, 1H, H-6), 8.52 (s, 1H, OH), 9.32 (s, 1H,
OH), 10.23 (s, 1H, CHO); 13C NMR (CDCl3+1 drop of
DMSO-d6, 50 MHz) d 60.9 (CH3), 105.6 (C), 108.9 (CH),
129.0 (C), 141.6 (C), 148.3 (C), 150.0 (C), 191.7 (CHO).
1
4.7.2. 2,6-Dibromo-3,5-dihydroxy-4-methoxybenzalde-
dyde (15). Mp 149–151 ꢁC; IR (KBr) nmax (cmꢀ1) 3439,
3272, 2944, 2904, 1682, 1560, 1481, 1437; 1H NMR
(CDCl3+1 drop of DMSO-d6, 200 MHz) d 3.75 (s, 3H,
OMe), 8.72 (br s, 2H, 2ꢂOH), 10.03 (s, 1H, CHO).
42%) as a yellow oil. H NMR (200 MHz) d 3.88 (s, 3H,
OMe), 4.03 (s, 3H, OMe), 6.53 (s, 1H, OH), 7.33 (s, 1H,
H-6), 10.23 (s, 1H, CHO).
4.10. 5-Benzyloxy-2-bromo-3,4-dimethoxybenzaldehyde
(4a)
4.8. General procedure for the O-benzylation of 14
Benzyl bromide (680 mL, 5.7 mmol) was added to a mixture
of 18 (1.23 g, 4.7 mmol) and potassium carbonate (0.98 g,
7.1 mmol) in DMF (40 mL). The mixture was heated at
50 ꢁC for 1.5 h. After cooling, it was portioned between
NaH (50% dispersion in mineral oil, 0.058 g, 1 mmol) was
added to a solution of benzaldehyde (20) (0.243 g,
14 mmol) in DMF (0.2 M, 5 mL) at room temperature under

S. Radix, R. Barret / Tetrahedron 63 (2007) 12379–12387
12385
AcOEt and water. The aqueous phase was extracted with
AcOEt. The combined organic layers were washed with
brine and water, dried over MgSO4, filtered and evaporated.
The crude residue was chromatographed on silica gel (PE/
AcOEt: 90:10) to give benzaldehyde (4a) (1.46 g, 88%) as
a colourless oil. IR (NaCl) nmax (cmꢀ1) 3066, 3033, 2939,
2868, 1683, 1575, 1497, 1478, 1454, 1426, 1403, 1378,
1329, 1284, 1242, 1214, 1184, 1164, 1098, 1044, 1005, 931,
5.96%. C31H28O5 requires C, 77.48%; H, 5.87%; IR (KBr)
nmax (cmꢀ1) 3058, 3029, 2931, 2870, 1605, 1564, 1473,
1462, 1433, 1393, 1375, 1352, 1281, 1228, 1152, 1112,
1070, 1054, 1008, 852, 786, 755, 722, 697; 1H NMR
(CDCl3, 200 MHz) d 4.03 (s, 3H, OMe), 4.06 (s, 6H,
2ꢂOMe), 5.29 (s, 2H, CH2), 5.32 (s, 2H, CH2), 7.17 (s,
1H, H-1), 7.35–7.61 (m, 12H, H-6, H-10, H-arom), 8.08
(d, 1H, J 9.5 Hz, H-9), 9.24 (d, 1H, J 9.5 Hz, H-5); 13C
NMR (CDCl3, 50 MHz) d 60.4 (CH3), 61.4 (2ꢂCH3), 70.8
(CH2), 71.5 (CH2), 107.2 (CH, C-1), 115.5 (CH, C-6),
119.2 (C, C-4a), 120.3 (CH, C-9), 123.2 (CH, C-5), 125.4
(C, C-4b), 127.1 (CH, C-10), 127.4 (2ꢂCH-arom), 127.42
(2ꢂCH-arom), 127.7 (C, C-8a), 127.9 (CH-arom para),
128.0 (CH-arom para), 128.6 (2ꢂCH-arom), 128.7
(2ꢂCH-arom), 129.2 (C, C-10a), 136.9 (C, C-arom ipso),
137.5 (C, C-arom ipso), 143.3 (C, C-3), 144.1 (C, C-8),
148.0 (C, C-2), 151.2 (C, C-7), 152.2 (C, C-4); MS (EI)
m/z 983 (2M++Na), 503 (2M++Na), 481 (MH+), 449, 412,
390, 299, 271, 256.
1
911, 851, 815, 733, 698, 677, 605; H NMR (300 MHz)
d 3.92 (s, 3H, OMe), 3.99 (s, 3H, OMe), 5.15 (s, 2H,
CH2), 7.32–7.48 (m, 6H, H-6, H-arom), 10.28 (s, 1H, CHO).
4.11. 1-Benzyloxy-4-bromo-5-[(Z)-2-(3-benzyloxy-2-
methoxyphenyl)-vinyl]-2,3-dimethoxy-benzene (3a)
Under nitrogen atmosphere, benzyl bromide (5) (1.20 g,
3.45 mmol) was treated with triphenylphosphine (1.03 g,
3.92 mmol) in DMF (15 mL) at 110 ꢁC for 1 h. After com-
plete formation of the phosphonium salt, the solution was
cooled to 90 ꢁC and a solution of benzaldehyde (4a)
(1.46 g, 4.1 mmol) in DMF (8 mL) was added, followed
by dropwise addition of a solution of methyl lithium
(1.6 M in Et2O, 2.5 mL, 4.0 mmol) in methanol (7 mL).
The colour of the solution changed to yellow. Heating and
stirring were continued for 16 h. The cooled reaction mix-
ture was poured into water and extracted with AcOEt. The
combined organic extracts were washed with water, dried
(Na2SO4), filtered and evaporated. The crude residue was
chromatographed on silica gel (PE/AcOEt: 92:8) to give
stilbene (3a) (1.44 g, 74%) as a white solid. Mp 88–89 ꢁC.
Found C, 66.11%; H, 5.41%. C31H29BrO5 requires C,
66.31%; H, 5.21%; IR (KBr) nmax (cmꢀ1) 3066, 3032,
2937, 2830, 1573, 1556, 1499, 1475, 1465, 1427, 1387,
1332, 1290, 1161, 1097, 1050, 1010, 858, 796, 749, 700;
1H NMR (CDCl3, 200 MHz) d 3.85 (s, 3H, OMe), 3.90 (s,
3H, OMe), 3.93 (s, 3H, OMe), 4.66 (s, 2H, CH2), 5.14 (s,
2H, CH2), 6.62–6.86 (m, 6H, H-6, H-vinyl, H-arom),
7.12–7.49 (m, 10H, H-arom); 13C NMR (CDCl3, 50 MHz)
d 60.8 (CH3), 61.1 (CH3), 61.3 (CH3), 70.9 (CH2), 70.9
(CH2), 111.0 (C), 111.6 (CH), 113.7 (CH), 122.7
(CH), 123.5 (CH), 126.4 (CH), 127.1 (2ꢂCH), 127.3
(2ꢂCH), 127.9 (CH), 128.0 (CH), 128.5 (2ꢂCH), 128.6
(2ꢂCH), 129.9 (CH), 131.2 (C), 132.8 (C), 136.7 (C),
137.1 (C), 142.9 (C), 147.9 (C), 151.0 (C), 151.3 (C),
152.0 (C); MS (EI) m/z 562 (M+ [81Br]), 560 (M+ [79Br]),
390, 299, 91; HRMS (EI) found (M+) 560.1197,
C31H2979BrO5 requires 560.1198.
4.13. Confusarin (1)
Dibenzyloxy phenanthrene (20) (0.521 g, 1.08 mmol) and
Pd/C (45 wt %) were mixed in AcOEt (30 mL). The required
pressure of hydrogen (20 bar) was then introduced. The
reaction mixture was stirred at room temperature for 24 h.
The excess pressure was vented and the reaction mixture
was filtered on CeliteÒ and evaporated. The crude residue
was chromatographed on silica gel (PE/AcOEt: 80:20) to
give confusarin (1) (0.275 g, 85%) as a white solid. Mp
185–187 ꢁC (lit.1a 185 ꢁC). Found C, 67.69%; H, 5.71%.
C17H16O5 requires C, 67.99%; H, 5.37%; IR (KBr) nmax
(cmꢀ1) 3286, 3005, 2983, 2932, 2832, 1623, 1605, 1575,
1542, 1486, 1450, 1174, 1159, 1099, 827, 815, 797, 782,
756, 715; 1H NMR (CDCl3+1 drop of DMSO-d6,
200 MHz) d 3.87 (s, 3H, OCH3), 3.88 (s, 3H, OCH3), 3.97
(s, 3H, OCH3), 6.40 (br s, 2H, 2ꢂOH), 7.06 (s, 1H, H-1),
7.18 (d, 1H, J 9.3 Hz, H-6), 7.44 (d, 1H, J 9.1 Hz, H-9),
7.81 (d, 1H, J 9.1 Hz, H-10), 9.04 (d, 1H, J 9.3 Hz, H-5);
13C NMR (CDCl3+1 drop of DMSO-d6, 50 MHz) d 59.8
(OCH3), 61.2 (OCH3), 61.5 (OCH3), 108.6 (CH, C-1),
117.0 (CH, C-6), 118.7 (C, C-4a), 119.5 (CH, C-9), 123.5
(CH, C-5), 124.5 (C, C-4b), 126.7 (C, C-8a), 127.00 (CH,
C-10), 129.2 (C, C-10a), 141.3 (C, C-3), 141.5 (C, C-8),
145.9 (C, C-7), 148.3 (C, C-2), 151.1 (C, C-4); MS (EI)
m/z 300 (M+), 285, 253, 242, 227, 199, 167.
4.14. 4-(Benzyloxy)-2-bromo-3,5-dimethoxybenzalde-
hyde (4b)
4.12. 2,7-Dibenzyloxy-3,4,8-trimethoxy-phenanthrene
(20)
Benzyl bromide (1.85 mL, 15.5 mmol) was added to a mix-
ture of 2-bromosyringaldehyde (3.36 g, 13 mmol) and potas-
sium carbonate (2.67 g, 19 mmol) in DMF (55 mL). The
mixture was heated at 50 ꢁC for 1.5 h. After cooling, it
was portioned between toluene and water. The aqueous
phase was extracted with toluene. The combined organic
layers were washed with water, dried over Na2SO4, filtered
and evaporated. The crude residue was chromatographed
on silica gel (PE/AcOEt: 95:5) to give benzaldehyde (4b)
(4.05 g, 89%) as a white solid. Mp 58 ꢁC; IR (KBr) nmax
(cmꢀ1) 3060, 3020, 2940, 2840, 1680, 1560, 1450, 1187,
1160, 1040, 980, 960, 920, 740; 1H NMR (CDCl3,
200 MHz) d 3.90 (s, 3H, OMe), 3.92 (s, 3H, OMe), 5.17
Under nitrogen atmosphere, to a solution of stilbene (3a)
(0.887 g, 1.6 mmol) in degassed toluene (20 mL) was added
dropwise a solution of AIBN (0.134 g, 0.82 mmol) and
Bu3SnH (550 mL, 2 mmol) in degassed toluene (20 mL) at
room temperature. After refluxing for 6.5 h, the cooled reac-
tion mixture was poured into water. The aqueous phase was
extracted with chloroform. The combined organic extracts
were washed with a saturated aqueous solution of KF and
water, dried (Na2SO4), filtered and evaporated. The crude
residue was recrystallised from PE/AcOEt/Et2O to give
dibenzyloxy phenanthrene (20) (0.461 g, 60%) as a pale
yellow solid. Mp 143–145 ꢁC. Found C, 77.23%; H,

12386
S. Radix, R. Barret / Tetrahedron 63 (2007) 12379–12387
(s, 2H, CH2), 7.32–7.51 (m, 6H, H-6, H-arom), 10.31 (s, 1H,
CHO); 13C NMR (CDCl3, 50 MHz) d 56.3 (CH3), 61.3
(CH3), 75.6 (CH2), 107.6 (CH), 115.6 (C), 128.3 (CH),
128.4 (2ꢂCH), 128.5 (2ꢂCH), 129.1 (C), 136.8 (C), 147.7
(C), 151.3 (C), 153.4 (C), 191.1 (CHO); MS (EI) m/z 352
(M+, [81Br]), 350 (M+, [79Br]), 324, 322, 271, 91.
dibenzyloxy phenanthrene (21) (0.547 g, 60%) as a white
solid. Mp 116–118 ꢁC. Found C, 77.24%; H, 5.80%.
C31H28O5 requires C, 77.48%; H, 5.87%; UV (CHCl3;
c¼5.6ꢂ10ꢀ5 mol lꢀ1) 311 (log 3 4.10), 348 (3.38), 365
(3.41); IR (KBr) nmax (cmꢀ1) 3095, 3060, 2960, 2940, 2840,
1620, 1565, 1500, 1480, 1455, 1195, 1160, 1120, 1070,
1015, 760, 730, 700; 1H NMR (CDCl3, 200 MHz) d 4.00 (s,
3H, OMe), 4.05 (s, 3H, OMe), 4.08 (s, 3H, OMe), 5.20 (s,
2H, CH2), 5.34 (s, 2H, CH2), 7.12 (s, 1H, H-1), 7.32–7.47
(m, 7H, H-arom), 7.54–7.67 (m, 5H, H-arom), 8.12 (d, 1H, J
9.3 Hz, H-9), 9.28 (d, 1H, J 9.3 Hz, H-5); 13C NMR (CDCl3,
50 MHz) d 55.9 (CH3), 60.4 (CH3), 61.4 (CH3), 71.5 (CH2),
75.7 (CH2), 105.5 (CH, C-1), 115.6 (CH, C-6), 119.00 (C,
C-4a), 120.3 (CH, C-9), 123.2 (CH, C-5), 125.44 (C, C-4b),
127.1 (CH, C-10), 127.4 (2ꢂCH-arom), 127.6 (C, C-8a),
127.96 (2ꢂCH-arom), 127.99 (CH-arom), 128.4 (CH-arom),
128.42 (2ꢂCH-arom), 128.6 (2ꢂCH-arom), 129.5 (C, C-
10a), 137.5 (C, C-arom ipso), 137.9 (C, C-arom ipso), 141.9
(C, C-3), 144.2 (C, C-8), 148.0 (C, C-4), 152.4 (C, C-7),
152.44 (C, C-2); MS (EI) m/z 503 (M++Na), 481 (MH+),
449, 412, 390, 359, 299.
4.15. General procedure for the synthesis of (Z)-3b and
(E)-3b
Under nitrogen atmosphere, benzyl bromide (5) (1.108 g,
3.51 mmol) was treated with triphenylphosphine (0.926 g,
3.53 mmol) in DMF (12 mL) at 110 ꢁC for 1 h. After com-
plete formation of the phosphonium salt, the solution was
cooled to 90 ꢁC and a solution of benzaldehyde (4b)
(1.234 g, 3.51 mmol) in DMF (6 mL) was added, followed
by dropwise addition of a solution of methyl lithium
(1.6 M dans Et2O, 2.2 mL, 3.52 mmol) in methanol
(5 mL). The colour of the solution changed to yellow. Heat-
ing and stirring were continued for 15 h. The cooled reaction
mixture was poured into water and extracted with AcOEt.
The combined organic extracts were washed with water,
dried (Na2SO4), filtered and evaporated. The crude residue
was chromatographed on silica gel (PE/AcOEt: 96:4) to
give stilbene (Z)-3b (1.146 g, 58%) as a white solid and stil-
bene (E)-3b (0.354 g, 18%) as a yellow oil.
4.17. 2,4,8-Trimethoxyphenanthrene-3,7-diol (2)
Dibenzyloxy phenanthrene (21) (0.422 g, 0.88 mmol) and
Pd/C (45 wt %) were mixed in AcOEt (30 mL). The required
pressure of hydrogen (20 bar) was then introduced. The
reaction mixture was stirred at room temperature for 24 h.
The excess pressure was vented and the reaction mixture
was filtered on CeliteÒ and evaporated. The crude residue
was chromatographed on silica gel (PE/AcOEt: 80:20) to
give phenanthrene (2) (0.228 g) as a yellow oil, which was
triturated in petroleum ether to obtain a white solid (0.179 g,
70%). Mp 149–150 ꢁC (lit.1e 152 ꢁC). Found C, 67.66%;
H, 5.54%. C17H16O5 requires C, 67.99%; H, 5.37%; IR
(KBr) nmax (cmꢀ1) 3490, 3440, 3020, 2975, 2940, 1615,
1580, 1510, 1480, 1440, 1195, 1170, 1100, 1050, 805,
710; UV (EtOH; c¼9ꢂ10ꢀ5 mol lꢀ1) 311 (log 3 3.95), 345
4.15.1. 2-Benzyloxy-4-bromo-5-[(Z)-2-(3-benzyloxy-2-
methoxyphenyl)-vinyl]-1,3-dimethoxy-benzene (Z)-3b.
Mp 107–109 ꢁC; IR (KBr) nmax (cmꢀ1) 3061, 3027,
2934, 1573, 1475, 1463, 1429, 1167, 1102, 1050, 785,
744, 710; 1H NMR (CDCl3, 200 MHz) d 3.38 (s, 3H,
OMe), 3.91 (s, 3H, OMe), 3.92 (s, 3H, OMe), 5.03 (s,
2H, CH2), 5.13 (s, 2H, CH2), 6.51 (s, 1H, H-6), 6.62–
6.88 (m, 5H, H-vinyl, H-arom), 7.32–7.50 (m, 10H, H-
arom); 13C NMR (CDCl3, 50 MHz) d 55.7 (CH3), 60.8
(CH3), 61.1 (CH3), 70.8 (CH2), 75.4 (CH2), 109.8 (CH),
110.4 (C), 113.8 (CH), 122.7 (CH), 123.4 (CH), 126.5
(CH), 127.3 (2ꢂCH), 127.98 (CH), 128.04 (CH), 128.3
(4ꢂCH), 128.6 (2ꢂCH), 130.15 (CH), 131.22 (C), 133.1
(C), 137.1 (C), 137.4 (C), 141.2 (C), 147.9 (C), 151.2 (C),
151.8 (C), 152.3 (C); MS (EI) m/z 562 (MH+), 561 (M+),
481, 451, 391, 361, 329, 301, 271, 255, 240, 207, 165,
137, 91, 85, 71, 67.
1
(3.39), 363 (3.45); H NMR (CDCl3, 200 MHz) d 3.96 (s,
3H, OCH3), 3.99 (s, 3H, OCH3), 4.05 (s, 3H, OCH3), 5.91
(br s, 1H, OH), 6.08 (br s, 1H, OH), 7.10 (s, 1H, H-1),
7.33 (d, 1H, J 9.3 Hz, H-6), 7.64 (d, 1H, J 9.0 Hz, H-9),
7.84 (d, 1H, J 9.0 Hz, H-10), 9.18 (d, 1H, J 9.3 Hz, H-5);
13C NMR (CDCl3, 50 MHz) d 56.2 (OCH3), 59.9 (OCH3),
61.9 (OCH3), 105.0 (CH, C-1), 116.1 (CH, C-6), 118.0 (CH,
C-9), 119.2 (C, C-4a), 124.0 (CH, C-5), 124.3 (C, C-4b),
125.8 (C, C-8a), 126.6 (C, C-10a), 127.5 (CH, C-10),
139.4 (C, C-3), 140.8 (C, C-8), 144.1 (C, C-4), 145.6 (C,
C-7), 146.9 (C, C-2); MS (EI) m/z 623 (2M++Na), 470,
416, 402, 345, 323 (M++Na), 301 (MH+), 269.
4.15.2. 2-Benzyloxy-4-bromo-5-[(E)-2-(3-benzyloxy-2-
methoxyphenyl)vinyl]-1,3-dimethoxy-benzene (E)-3b. H
1
NMR (200 MHz) d 3.93 (s, 9H, 3ꢂOMe), 5.08 (s, 2H, CH2),
5.17 (s, 2H, CH2), 6.66–7.10 (m, 4H), 7.26–7.58 (m, 12H).
4.16. 3,7-Dibenzyloxy-2,4,8-trimethoxy-phenanthrene
(21)
Acknowledgements
Under nitrogen atmosphere, to a solution of stilbene (Z)-3b
(0.906 g, 1.6 mmol) in degassed toluene (12 mL) was added
dropwisea solutionofAIBN (0.134 g, 0.8 mmol)andBu3SnH
(560 mL, 2.08 mmol) in degassed toluene (8 mL) at room tem-
perature. After refluxing for 5 h, the cooled reaction mixture
was poured into water. The aqueous phase was extracted
with chloroform. The combined organic extracts were washed
with a saturated aqueous solution of KF and water, dried
(Na2SO4), filtered and evaporated. The crude residue was
chromatographed on silica gel (PE/AcOEt: 96:4) to give
The authors are grateful to ‘PIERRE FABRE Dermo-
ꢀ
Cosmetique Co.’ for financial support and to Pascal Bordat
and Roger Tarroux for fructuous discussions.
References and notes
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