Alternative simple and effective synthesis of (di)benzoxanthones and their functions toward fluorescent dyes

Article abstract of DOI:10.1016/j.tet.2012.12.035

(Di)benzoxanthones possessing additional benzene units on one or both sides of xanthone were prepared via dehydration of the corresponding dihydroxybenzophenone, where a catalytic amount of K₂CO₃ dramatically increased the yields. Chemical transformations of the versatile carbonyl groups of (di)benzoxanthones could derive fluorescent materials.

Full text of DOI:10.1016/j.tet.2012.12.035

Tetrahedron 69 (2013) 1694e1699
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Alternative simple and effective synthesis of (di)benzoxanthones
and their functions toward fluorescent dyes
*
Eriko Azuma, Kouji Kuramochi, Kazunori Tsubaki
Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Shimogamo, Sakyo-ku, Kyoto 606-8522, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 1 October 2012
Received in revised form 10 December 2012
Accepted 16 December 2012
Available online 21 December 2012
(Di)benzoxanthones possessing additional benzene units on one or both sides of xanthone were pre-
pared via dehydration of the corresponding dihydroxybenzophenone, where a catalytic amount of K2CO3
dramatically increased the yields. Chemical transformations of the versatile carbonyl groups of (di)
benzoxanthones could derive fluorescent materials.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
(Di)benzoxanthone
Xanthone
Fluorescence
Intramolecular dehydration
1. Introduction
as well as under acidic conditions using a catalytic amount of
10
H2SO4 or melting pyridinium hydrochloride.4d,8b Additionally,
Xanthone skeletons, which commonly occur in natural prod-
ucts,1 exhibit various pharmacological activities (e.g., anti-cancer
and anti-bacterial properties)2 and in the medicinal chemistry
field, are frequently valued as effective pharmacophores.3 Addi-
tionally, xanthone skeletons frequently display fluorescent re-
sponses, which have facilitated the development of fluorescent
dyes derived from xanthone as a key fragment.4 Consequently,
much effort has been devoted to effectively synthesize xanthones.
Larock et al. have constructed various xanthones though arynes and
CeH activation.5 Recently, xanthones have been constructed under
mild conditions using palladium-catalyzed oxidative double CeH
carbonylation of biarylethers.6 Although many synthetic routes
have been reported, cyclization from the benzophenone possessing
the proper functional groups on the scaffolding 2,20-positions re-
mains the most common.
Xanthone synthetic routes are classified roughly into two
groups according to the functional groups on the 2,20-positions: (1)
cyclization from 2-hydroxy-20-halogen or alkoxy benzophenones
under basic conditions though ipso-substitution7 and (2) dehy-
drative cyclization from 2,20-dihydroxybenzophenones under
(mainly) harsh conditions. The latter route is further divided
according to the reaction conditions. Dehydrative cyclization has
been reported to occur under neutral conditions at high tempera-
ture in water using a sealed tube8 or SiO2 as a dehydration reagent,9
there are a few cases where dehydrative cyclization occurs under
basic conditions using ethanolic KOH or a large excess of sodium
acetate.11
On the other hand, our research focuses on colorimetric mo-
lecular recognition based on phenolphthalein with two crown
loops. To date, we have successfully visualized features of guest
molecules, such as chirality, shape, and size.12 In particular, our
work has targeted spermidine and spermine, which are biogenic
polyamines, to develop a practical method to determine the sper-
midine level in living cells.13 We aim to change our molecular
recognition system from a color-response type to a fluorescent-
response type. We recently reported the exhaustive syntheses of
naphthofluoresceins possessing additional benzene units on one or
both sides of fluorescein, and revealed that some naphtho-
fluoresceins exhibit fluorescent emissions in the near infrared re-
gion (>700 nm) with large Stokes shifts and humble quantum
yields.14
To improve the quantum yields of the derivatives, we selected
(di)benzoxanthone skeletons as key intermediates due to the ver-
satility of the carbonyl groups of (di)benzoxanthones. These car-
bonyl groups can be converted into other functional groups
through Wittig reactions, organometallic reagents, etc. to afford
a variety of fluorescent molecules within a few reaction steps.4
Herein, we describe the exhaustive syntheses of nine (di)ben-
zoxanthones from their corresponding 2,20-dihydroxybenzop-
henones in the presence of a catalytic amount of K2CO3, as well as
their optical properties.
* Corresponding author. E-mail address: tsubaki@kpu.ac.jp (K. Tsubaki).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.12.035

E. Azuma et al. / Tetrahedron 69 (2013) 1694e1699
1695
2. Results and discussion
and cyclization under acidic conditions was not fruitful because
several fragmental products, such as 2,7-dihydroxynaphthalene (8%
yield) and 1,6-dihydroxy-naphthalene-2-carboxylic acid (17% yield)
were obtained instead of desired compound 7a, (entry 3).10,14 These
data indicate that in the case of compound 6a, a retro FriedeleCrafts
reaction predominantly occurs instead of the desired cyclization
under acidic conditions. It is interesting to note that in the case of
cyclization of compound 6d, which is a structural isomer of 6a, these
reactions proceed smoothly under identical conditions to give cor-
respondingdibenzoxanthone7dinquantitativeyield. Inentries411b,c
and 5,11e which are from the literature, cyclization under basic con-
ditions in an organic solvent was applied to give an inseparable and
complicated compound mixture. In contrast, reactions under basic
conditions in water11d or molten pyridinium hydrochloride4d,8b
produced desired 7a in moderate yields (entries 6 and 7). Because
a promising result was obtained in the presence of K2CO3 (0.1 equiv)
in water (entry 8), we modified the reaction conditions. Thus, the
reaction was performed at 150 ꢀC using a sealed tube, which in-
creased the yield of 7a to 99% (entry 9). Almost no influences of the
counter cations (including quaternary ammonium cation) were ob-
served (entries 9e14). Based on these observations, we estimate the
conditions in entry 9 (0.1 equiv of K2CO3, water, 150 ꢀC) are the most
appropriate. It is especially noteworthy that the product was easily
isolated from the reaction mixture; filtration isolated cyclized
dibenzoxanthone 7a from an acidified aqueous solution in an ex-
tremely pure form without chromatographic purification.
Scheme 1 shows the synthesis of dibenzoxanthone 7a. Bromo-
naphthalene 1a14 was lithiated by n-BuLi and trapped with DMF to
afford aldehyde 2a in 81% yield. The corresponding coupling partner
3a was treated with n-BuLi and allowed to react with aldehyde 2a to
give 4a in 93% yield. Dibenzylic alcohol 4a was oxidized by MnO2 in
72% yield. HCl in dioxane was then used to remove the four MOM
groups in compound 5a, producing cyclization precursor 6a in 96%
yield. The other precursors were synthesized by the same procedure
in moderate to good total yields (see Supplementary data). Table 1
shows the results of different reaction conditions on the intra-
molecular dehydration from precursor 6a to dibenzoxanthone 7a.
O
Br
H
(a)
RO
RO
OR
1a (R = MOM)
OR
(c)
2a
OR
OR
H
OH
(b)
Br
OR
With the optimal reaction conditions in hand, we then studied
the generality of substrates for the reaction using other dihydrox-
ybenzophenones 6bei (Fig. 1). Intramolecular dehydration
OR OR
4a
OR
3a
OR
OH
O
O
O
Table 1
O
K2CO3
Ar
Ar
O
Ar
Ar
H2O
150 °C
OH
HO
OR OR
O
HO
OH
OH OH
6b-i
OR
OH
7a
5a (R = MOM)
6a (R = H)
7b-i (time, yield%)
(d)
OH
OH
OH
Scheme 1. Syntheticroutefordibenzoxanthone7a. (a)n-BuLi, DMF, 81%yield;(b)n-BuLi,
2a, 93% yield; (c) MnO2, 72% yield; (d) HCl in dioxane, 96% yield.
O
O
Table 1
Dehydration from 6a to 7a
O
O
OH
7b (6h, 100%)
7c (10h, 86%)
Entry Solvent
Additive (equiv) Temp (ꢀC) Time (h) Yield of 7a (%)
O
18
H2O
d
d
150a
40
50
Reflux
Reflux
150
9
21
3.5
9
9
9
0.3b
No reaction
Decomposed
Mixture
Mixture
61
O
29
SiO2
d
310,14 MeSO3H
411b,c
511e
EtOH
CH3CN
KOH (1.0)
K2CO3 (3.0)
d
HO
OH
O
HO
O
64d,8b Py$HClc
OH
711d
8
9
10
11
12
13
14
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
AcONa (10)
K2CO3 (0.1)
K2CO3 (0.1)
Li2CO3 (0.1)
Na2CO3 (0.1)
Rb2CO3 (0.1)
Cs2CO3 (0.1)
Reflux
Reflux
150a
150a
150a
150a
150a
9
9
9
9
9
9
9
9
21
62
99
93
99
96
96
85
7d (180 °C, 18h, 85%)
7e (18h, 98%)
OH
O
O
O
(nBu)4NOH (0.1) 150a
O
OH
HO
HO
OH
7f (9h, 74%)
7g (9h, 98%)
O
a
Sealed tube condition.
b
c
Yield of 7a calculated based on the integral intensity of 1H NMR.
O
Pyridinium hydrochloride.
O
OH
O
OH
Dehydration in a sealed tube with neutral water and high tem-
perature (150 ꢀC),8 which are the standard conditions to form the
xanthone skeleton, did not proceed, and only a small amount of de-
sired 7a was detected by NMR (estimated in ca. 0.3% yield, entry 1).
Similarly, the reaction did not occur using SiO2 treatments (entry 2),9
7i4d (9h, 78%)
HO
7h (24h, 72%)
Fig. 1. Syntheses of (di)benzoxanthones 7bei.

1696
E. Azuma et al. / Tetrahedron 69 (2013) 1694e1699
occurred smoothly and afforded (di)benzoxanthones 7bei in good
to excellent yields after filtration.
Withrespecttocyclizationunderbasicconditions, weproposethe
following reaction mechanism (Fig. 2). K2CO3 acts as a weak base to
generate a monoanion of 2,20-dihydroxybenzophenone, which forms
a pseudo-eight-membered ring via an intramolecular hydrogen
bond. Then nucleophilic cyclization occurs through this conforma-
tion in a 6-exo-trig fashion. Finally, the hydroxy anion leaves, which
re-aromatizes the ringand leads toaxanthone. TheHOMOand LUMO
of the eight-membered monoanion (DFT/B3LYP/6-31þG (d, p)) may
support the plausible mechanism (see Supplementary data).15
Fig. 3. FL spectra of 7a, 7d, 7e, and 7f in methanol and picture of FL under UV light
(365 nm).
The quantum yields (F) dramatically decreased for compounds
7a, 7b, 7c, and 7g, which all possess at least one benzene ring fused
on the same side of the central carbonyl group. On the other hand,
compounds 7e and 7h displayed emissions near 490 nm with large
quantum yields (F). The same tendencies have been observed in
a series of naphthofluoresceins in a previous study.14
Finally, the diversity of products obtained from MOM-protected
dibenzoxanthone 8, which was prepared from 7e in 90% yield,
was demonstrated (Scheme 2). Phenyllithium easily reacted with
7e at ꢁ78 ꢀC in dry THF to give triarylalcohol 9 in 98%. The Wittig
reaction using methyltriphenylphosphonium bromide and n-BuLi
afforded exo methylene compound 10 in 47% yield. Additionally, the
carbonyl group on 7e was removed easily, giving 11 in 65% yield.8b
These products could be further converted into more useful com-
pounds for fluorescent dyes.
HO
RO
Fig. 2. Plausible mechanism for base catalyzed cyclization. (a) Optimized structure of
the monoanionic benzophenone with (b) HOMO and (c) LUMO obtained by DFT cal-
culations at the B3LYP/6-31þG (d, p) level.
Ph
(b)
O
Table 2 summarizes the optical properties of the (di)benzox-
anthones 7aei (lmax and ε of the absorbance, emission wave-
9 (R = MOM)
lengths, quantum yields (
absorption wavelengths for (di)benzoxanthones 7aei were dis-
tributed within narrow area between 352 nm (7g) and
F), and Stokes shifts). The maximum
OR
a
RO
O
RO
RO
CH2
(c)
(d)
380 nm (7d). However, these compounds can be roughly divided
into four groups based on the maximum emission wavelength
(
lem): (1) compounds 7f and 7i4d (400 nm<
l
em<440 nm), (2)
em<480 nm), (3) compounds
em<520 nm), and (4) compound
em<560 nm). The properties of this series of (di)
O
O
compounds 7a, b, and 7g (440 nm<
7c, 7e, and 7h (480 nm<
7d (520 nm<
l
10 (R = MOM)
7e (R = H)
l
l
8 (R = MOM)
OR
OR
OR
benzoxanthones 7aei are suitable for multi-color system applica-
tions with a single wavelength excitation in the chemical biology
field. For example, the combination of compounds 7f, 7a, 7e,
and 7d, whose maximum emission wavelengths are in ca. 40 nm
increments, is expected for multi-color fluorescence sensing
(Fig. 3).
H
H
O
11 (R = MOM)
Table 2
Optical properties of compounds 7aei in methanola
Compound lAbs max (nm) ε (lAbs max
)
lem (nm)
F
(%)b Stokes shift (nm)
Scheme 2. Transformation from dibenzoxanthone 8. (a) NaH, MOMCl, 90% yield; (b)
PhLi, ꢁ78 ꢀC, 98% yield; (c) Ph3PMeBr, n-BuLi, 47% yield; (d) BH3eTHF, 65% yield.
7a
7b
7c
7d
7e
7f
7g
7h
7i4d
367
356
374
380
358
368
352
353
357
16,000
18,000
22,000
15,000
21,000
11,000
15,000
21,000
10,000
475
478
507
528
494
420
480
493
413
4
0.4
2
105
98
133
154
134
58
122
138
53
7
3. Conclusions
46
18
5
48
28
We successfully constructed (di)benzoxanthones via de-
hydration of the corresponding dihydroxybenzophenones. We
synthesized all types of (di)benzoxanthones 7aei, and indicated the
possibility that a combination of compounds is expected for multi-
color fluorescence sensing (e.g., 7a, 7d, 7e, and 7f). Merits of this
reaction include simplicity, usefulness, and good atom economy.
a
UV and FL spectra of compounds 7aei, see Supplementary data.
b
Fluorescence quantum yields of 7aei (
F
) determined using a solution of quinine
¼0.546).
sulfate in 1 N H2SO4 as a reference standard (
F

E. Azuma et al. / Tetrahedron 69 (2013) 1694e1699
1697
Moreover, this reaction is environmentally benign because the
solvent is water and column purification is not employed. Currently
we are synthesizing various derivatives through (di)benzox-
anthones as the key intermediates for new fluorescent materials.
at room temperature for 12 h. The solid materials were filtered
through Celite, and the filtrate was concentrated under reduced
pressure to dryness. The residue was purified by column chro-
matography (SiO2; n-hexane/EtOAc¼5/1) to afford 5a (636.3 mg,
72% yield) as a yellow oil. IR (film) 2956, 1664, 1622, 1512, 1240,
4. Experimental
1151, 995, 829 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
8.37 (d, J¼8.8 Hz,
1H), 7.84 (d, J¼8.8 Hz, 1H), 7.76 (d, J¼8.8 Hz, 1H), 7.52 (d, J¼8.8 Hz,
1H), 7.40 (d, J¼8.8 Hz, 1H), 7.34 (d, J¼2.4 Hz, 1H), 7.31 (d, J¼8.8 Hz,
1H), 7.29 (d, J¼2.4 Hz, 1H), 7.27 (dd, J¼8.8, 2.4 Hz, 1H), 7.15 (dd,
J¼8.8, 2.4 Hz, 1H), 5.31 (s, 2H, eCH2OCH3), 5.14 (s, 2H, eCH2OCH3),
5.12 (s, 2H, eCH2OCH3), 5.04 (s, 2H, eCH2OCH3), 3.52 (s, 3H,
eCH2OCH3), 3.46 (s, 3H, eCH2OCH3), 3.37 (s, 3H, eCH2OCH3), 3.22
4.1. Compound 2a
A solution of n-BuLi (1.62 M n-hexane solution; 0.68 ml,
1.11 mmol) was added dropwise to a solution of 1a14 (330 mg,
1.01 mmol) in dry THF (5 ml) under N2 atmosphere at ꢁ78 ꢀC. After
1 h stirring, dry DMF (109
ml) was added dropwise to the solution.
(s, 3H, eCH2OCH3); 13C NMR (68 MHz, CDCl3)
d 196.2, 157.2, 156.2,
The resultant solution was stirred at ꢁ78 ꢀC for 1 h, and then
allowed to warm to room temperature. The reaction mixture was
poured into the mixed solvent of ethyl acetate and 0.1 M aq HCl. The
organic layer was separated and washed successively with water
and brine, dried over Na2SO4, filtered, and concentrated under re-
duced pressure to dryness. The residue was purified by column
chromatography (SiO2; n-hexane/EtOAc¼8/1) to afford 2a
(225.3 mg, 81% yield) as a pale yellow powder. Mp 53.5e54.0 ꢀC; IR
155.5, 152.7, 138.3, 132.8, 131.0, 129.6, 127.9, 126.5, 125.7, 125.4,
124.7, 124.5, 122.5, 119.3, 117.3, 113.4, 109.3, 106.9, 102.0, 94.6, 94.4,
94.2, 57.7, 56.3, 56.2, 56.1; MS (EIþ) m/z (rel int.) 522 (Mþ, 6), 461
(9), 445 (26), 429 (97), 385 (43), 341 (26), 292 (26), 216 (100), 186
(21), 71 (7); HRMS (EIþ) calcd for C29H30O9 (Mþ): 522.1890. Found:
522.1887. Anal. Calcd for C29H30O9: C, 66.66; H, 5.79. Found: C,
66.54; H, 5.70.
(KBr) 2881, 1676, 1626, 1471, 1240, 1157, 1009, 904 cmꢁ1
(270 MHz, CDCl3)
;
1H NMR
4.4. Compound 6a
d
10.46 (s, 1H, AreCHO), 8.16 (d, J¼8.9 Hz, 1H),
7.84 (d, J¼8.9 Hz, 1H), 7.56 (d, J¼8.9 Hz, 1H), 7.41 (d, J¼2.4 Hz, 1H),
7.30 (dd, J¼8.9, 2.4 Hz, 1H), 5.33 (s, 2H, eCH2OCH3), 5.27 (s, 2H,
eCH2OCH3), 3.66 (s, 3H, eCH2OCH3), 3.53 (s, 3H, eCH2OCH3); 13C
A solution of 4 M hydrogen chloride in 1,4-dioxane (17.9 ml)
was added dropwise to a solution of 5a (1.88 g, 3.60 mmol) in 1,4-
dioxane (15 ml) and stirred for 10 h at room temperature. The
solvent was evaporated in vacuo to afford crude 6a as brown foam
(1.20 g, 96% yield). Crude 6a was directly used for the next step
without further purification. IR (KBr) 3261, 1628, 1581, 1473, 1240,
NMR (68 MHz, CDCl3) d 189.7, 159.4, 157.7, 139.6, 125.3, 124.1, 123.9,
123.4, 123.4, 119.5, 110.2, 101.9, 94.2, 58.2, 56.3; MS (EIþ) m/z
(rel int.) 276 (Mþ, 63), 230 (100), 201 (21), 115 (27), 102 (18), 75
(8); HRMS (EIþ) calcd for C15H16O5 (Mþ): 276.0998. Found:
276.0997. Anal. Calcd for C15H16O5: C, 65.21; H, 5.84. Found: C,
65.22; H, 5.87.
831 cmꢁ1; 1H NMR (400 MHz, CD3OD)
d
8.36 (d, J¼8.8 Hz, 1H), 7.75
(d, J¼8.8 Hz, 1H), 7.67 (d, J¼8.8 Hz, 1H), 7.10 (d, J¼8.8 Hz, 1H), 7.03
(d, J¼8.8 Hz, 1H), 6.99 (s, 1H), 6.98 (d, J¼8.8 Hz, 1H), 6.91 (d,
J¼8.8 Hz, 1H), 6.88 (d, J¼8.8 Hz, 1H), 6.73 (s, 1H); 13C
4.2. Compound 4a
NMR (100 MHz, CD3OD) d 204.8, 164.6, 161.1, 157.7, 153.5, 141.8,
134.7, 132.2, 130.9, 129.2, 127.4, 124.4, 120.0, 118.8, 118.6, 118.2,
116.7, 115.5, 114.4, 110.5, 106.3; MS (FABþ) m/z (rel int.) 347 (MþHþ,
7), 241 (15), 185 (58), 149 (51), 93 (100), 75 (78), 57 (43), 45
(26); HRMS (FABþ) calcd for C21H14O5 (Mþ): 346.0841. Found:
346.0841. Anal. Calcd for C21H14O5: C, 72.83; H, 4.07. Found: C,
72.54; H, 4.10.
A solution of n-BuLi (1.59 M n-hexane solution; 1.42 ml,
2.26 mmol) was added dropwise to a solution of 3a14 (677.4 mg,
2.07 mmol) in dry THF (15 ml) under N2 atmosphere at ꢁ78 ꢀC.
After 1 h stirring, a solution of 2a (520 mg, 1.88 mmol) in THF (5 ml)
was added dropwise to the solution at ꢁ78 ꢀC. The resultant so-
lution was allowed to warm to room temperature with stirring for
5 h. The reaction mixture was poured into the mixed solvent of
ethyl acetate and 0.1 M aq HCl. The organic layer was successively
washed with water and brine, dried over Na2SO4, filtered, and
concentrated under reduced pressure to dryness. The residue was
purified by column chromatography (SiO2; n-hexane/EtOAc¼4/1)
to afford 4a (915.3 mg, 93% yield) as pale yellow oil. IR (film) 3500,
4.5. General procedure for the preparation of xanthones 7aei
The preparation of 7a is typical. A suspension of 6a (50 mg,
0.144 mmol), K2CO3 (2.0 mg, 0.014 mmol) in water (8.0 ml) in
a pressure tube was stirred for 9 h at 150 ꢀC. To the reaction mix-
ture, 1 M aq HCl was added and the insoluble matter was collected
by filtration to afford 7a (47.1.9 mg, 99% yield) as a pale gray
powder.
1626, 1514, 1236, 1151, 999, 831 cmꢁ1 1H NMR (270 MHz, CDCl3)
;
d
8.09 (d, J¼8.9 Hz, 1H), 7.86 (d, J¼2.4 Hz, 1H), 7.73 (d, J¼8.9 Hz, 1H),
7.70 (d, J¼8.9 Hz,1H), 7.36e7.30 (m, 4H), 7.23 (dd, J¼8.9, 2.4 Hz,1H),
7.15 (d, J¼7.3 Hz, 1H, Ar2CHOH), 7.10 (dd, J¼8.9, 2.4 Hz, 1H),
5.32e5.24 (m, 6H, eCH2OCH3), 5.19 (ABq, Dn¼25.7 Hz, JAB¼6.5 Hz,
2H, eCH2OCH3), 4.82 (d, J¼7.3 Hz, 1H, Ar2CHOH), 3.74 (s, 3H,
eCH2OCH3), 3.50 (s, 3H, eCH2OCH3), 3.46 (s, 3H, eCH2OCH3), 3.40
4.5.1. Compound 7a. Mp >300 ꢀC; IR (KBr) 3136, 1635, 1597, 1577,
1442, 1219, 1159, 1022, 827 cmꢁ1 1H NMR (400 MHz, DMSO-d6)
;
d
10.47 (s, 1H, ArOH), 10.24 (s, 1H, ArOH), 9.48 (d, J¼2.4 Hz, 1H), 8.58
(d, J¼8.8 Hz, 1H), 8.27 (d, J¼8.8 Hz, 1H), 8.11 (d, J¼8.8 Hz, 1H), 7.95
(d, J¼8.8 Hz, 1H), 7.72 (d, J¼8.8 Hz, 1H), 7.69 (d, J¼8.8 Hz, 1H), 7.33
(dd, J¼8.8, 2.4 Hz, 1H), 7.32 (d, J¼2.4 Hz, 1H), 7.19 (dd, J¼8.8, 2.4 Hz,
(s, 3H, eCH2OCH3); 13C NMR (68 MHz, CDCl3)
d 155.2, 155.1, 152.9,
151.3, 135.6, 133.4, 130.7, 129.7, 129.3, 126.4, 126.0, 124.3, 124.0,
123.4, 122.8, 118.8, 116.8, 113.9, 109.8, 107.6, 100.8, 95.1, 94.3, 94.3,
67.3, 57.8, 56.5, 56.1, 56.0; MS (EIþ) m/z (rel int.) 524 (Mþ, 5), 476 (5),
401 (100), 357 (40), 313 (19), 216 (42), 169 (15), 115 (29), 69 (25);
HRMS (EIþ) calcd for C29H32O9 (Mþ): 524.2046. Found: 524.2048.
Anal. Calcd for C29H32O9: C, 66.40; H, 6.15. Found: C, 66.56; H, 6.01.
1H); 13C NMR (100 MHz, DMSO-d6)
d 177.2, 159.1, 157.4, 151.9, 138.2,
136.4, 132.6, 130.6, 124.7, 124.6, 123.3, 121.6, 119.4, 117.8, 116.8, 116.8,
114.5, 113.4, 110.3, 109.5 (one peak overlapped); MS (FABþ) m/z (rel
int.) 329 (MþHþ, 36), 185 (54), 149 (45), 93 (100), 75 (73), 57 (43),
45 (29); HRMS (FABþ) calcd for C21H13O4 (MþHþ): 329.0814.
Found: 329.0812. Anal. Calcd for C21H12O4$1/4H2O: C, 75.78; H,
3.79. Found: C, 75.88; H, 3.67.
4.3. Compound 5a
To a solution of 4a (890 mg, 1.70 mmol) in CH2Cl2 (50 ml),
manganese dioxide (8.9 g) was added. The suspension was stirred
4.5.2. Compound 7b. Yield 100%; pale gray powder; mp >300 ꢀC;
IR (KBr) 3325, 1633, 1591, 1533, 1444, 1257, 1242, 1217, 823 cmꢁ1; 1H

1698
E. Azuma et al. / Tetrahedron 69 (2013) 1694e1699
NMR (270 MHz, DMSO-d6)
d
10.21 (s, 2H, ArOH), 9.49 (s, 2H), 8.23
117 (30), 93 (100), 75 (83), 57 (48); HRMS (FABþ) calcd for C17H11O4
(d, J¼8.6 Hz, 2H), 7.95 (d, J¼8.6 Hz, 2H), 7.51 (d, J¼8.6 Hz, 2H), 7.20
(MþHþ): 279.0657. Found: 279.0661.
(d, J¼8.6 Hz, 2H); 13C NMR (68 MHz, DMSO-d6)
d 179.3, 158.7, 155.8,
136.0, 132.1, 130.4, 124.4, 117.4, 114.2, 113.6, 109.3; MS (EIþ) m/z (rel
int.) 328 (Mþ, 19), 256 (7), 232 (31), 193 (41), 178 (100), 177 (100),
135 (88), 97 (100), 91 (87); HRMS (EIþ) calcd for C21H12O4 (Mþ):
328.0736. Found: 328.0738. Anal. Calcd for C21H12O4$1/4H2O: C,
75.78; H, 3.79. Found: C, 75.82; H, 3.75.
4.5.8. Compound 7h. Yield 72%; gray powder; mp >300 ꢀC; IR (KBr)
3423, 3170, 1606, 1489, 1267, 1163, 850 cmꢁ1 1H NMR (400 MHz,
;
DMSO-d6)
d 10.96 (s, 1H, ArOH), 10.35 (s, 1H, ArOH), 8.69 (s, 1H),
8.08 (d, J¼8.8 Hz, 1H), 8.04 (d, J¼8.8 Hz, 1H), 7.80 (s, 1H), 7.20 (d,
J¼2.4 Hz, 1H), 7.12 (dd, J¼8.8, 2.4 Hz, 1H), 6.86 (dd, J¼8.8, 2.4 Hz,
1H), 6.83 (d, J¼2.4 Hz, 1H); 13C NMR (100 MHz, DMSO-d6)
d 175.5,
4.5.3. Compound 7c. Yield 86%; gray powder; mp >300 ꢀC; IR
164.4, 158.4, 158.2, 152.6, 138.6, 131.9, 128.5, 127.6, 124.6, 119.6,
118.5, 113.7, 113.6, 111.0, 107.4, 102.3; MS (FABþ) m/z (rel int.) 279
(MþHþ, 22), 185 (50), 149 (29), 93 (100), 75 (59), 57 (40); HRMS
(FABþ) calcd for C17H11O4 (MþHþ): 279.0657. Found: 279.0658.
Anal. Calcd for C17H10O4$1/3H2O: C, 71.83; H, 3.78. Found: C, 72.03;
H, 3.57.
(KBr) 3255, 1699, 1618, 1535, 1483, 1437, 1360, 1221, 1186,
849 cmꢁ1 1H NMR (400 MHz, DMSO-d6)
; d 10.38 (s, 1H, ArOH),
10.27 (s, 1H, ArOH), 9.40 (d, J¼2.4 Hz, 1H), 8.79 (s, 1H), 8.23 (d,
J¼8.8 Hz, 1H), 8.12 (d, J¼8.8 Hz, 1H), 7.91 (d, J¼8.8 Hz, 1H), 7.90 (s,
1H), 7.44 (d, J¼8.8 Hz, 1H), 7.24 (d, J¼2.4 Hz, 1H), 7.16 (dd, J¼8.8,
2.4 Hz, 1H), 7.15 (dd, J¼8.8, 2.4 Hz, 1H); 13C NMR (100 MHz, DMSO-
d6)
d
178.2, 159.4, 158.5, 158.3, 151.4, 138.3, 137.3, 132.9, 131.9,
4.5.9. Compound 7i. Yield 78%; yellow powder; mp >300 ꢀC; IR
130.7, 127.5, 125.0, 124.3, 119.9, 119.8, 117.4, 114.5, 111.9, 110.7,
109.5, 107.4; MS (FABþ) m/z (rel int.) 329 (MþHþ, 23), 241 (17), 185
(60), 149 (51), 117 (29), 93 (100), 75 (76), 57 (52), 45 (35); HRMS
(FABþ) calcd for C21H13O4 (MþHþ): 329.0814. Found: 329.0811.
Anal. Calcd for C21H12O4$1/3H2O: C, 75.44; H, 3.82. Found: C,
75.84; H, 3.66.
(KBr) 3375, 1630, 1616, 1570, 1394, 1254, 1194, 845 cmꢁ1 1H NMR
;
(400 MHz, DMSO-d6) d 10.94 (s, 1H, ArOH), 10.44 (s, 1H, ArOH), 8.52
(d, J¼8.8 Hz, 1H), 8.06 (d, J¼8.8 Hz, 1H), 7.98 (d, J¼8.8 Hz, 1H), 7.65
(d, J¼8.8 Hz, 1H), 7.30 (dd, J¼8.8, 2.4 Hz, 1H), 7.29 (d, J¼2.4 Hz, 1H),
7.09 (d, J¼2.4 Hz, 1H), 6.95 (dd, J¼8.8, 2.4 Hz, 1H); 13C NMR
(100 MHz, DMSO-d6)
d 174.6, 163.6, 159.1, 157.3, 153.5, 138.4, 127.8,
124.8, 122.8, 121.5, 119.4, 117.1, 114.9, 114.7, 114.6, 110.2, 102.7; MS
(FABþ) m/z (rel int.) 279 (MþHþ, 17), 241 (15), 185 (56), 149 (50), 117
(27), 93 (100), 75 (81), 57 (46); HRMS (FABþ) calcd for C17H11O4
(MþHþ): 279.0657. Found: 279.0659. Anal. Calcd for C17H10O4$2/
3H2O: C, 70.34; H, 3.94. Found: C, 70.60; H, 3.78.
4.5.4. Compound 7d. Yield 85%; pale gray powder; mp >300 ꢀC; IR
(KBr) 3269, 1624, 1610, 1469, 1356, 1180 cmꢁ1 1H NMR (400 MHz,
;
DMSO-d6)
d
10.42 (s, 2H, ArOH), 8.77 (s, 2H), 8.10 (d, J¼8.8 Hz, 2H),
7.80 (s, 2H), 7.22 (d, J¼2.4 Hz, 2H), 7.13 (dd, J¼8.8, 2.4 Hz, 2H); 13C
NMR (100 MHz, DMSO-d6)
d 176.8, 158.5, 152.5, 138.9, 131.8, 127.9,
124.1, 119.1, 117.8, 110.3, 107.2; MS (FABþ) m/z (rel int.) 329 (MþHþ,
5), 241 (12), 207 (18), 185 (51), 149 (49), 115 (54), 93 (100), 75 (82),
57 (47); HRMS (FABþ) calcd for C21H13O4 (MþHþ): 329.0814.
Found: 329.0821.
4.6. Compound 8
To a stirred solution of 7e (260 mg, 0.79 mmol) in dry DMF
(10 ml), NaH (60% dispersion in mineral oil, 76 mg, 1.90 mmol) was
added portionwise at room temperature. After 30 min, MOMCl
4.5.5. Compound 7e. Yield 98%; gray powder; mp >300 ꢀC; IR
(132.3 ml, 1.74 mmol) was added to the solution and stirred for 6.5 h
(KBr) 3398, 3107, 1647, 1622, 1597, 1481, 1390, 1365, 1259, 1173,
at room temperature. The reaction mixture was poured into the
mixed solvent of ethyl acetate and 0.1 M aq HCl. The organic layer
was separated and washed successively with water and brine. After
dried over sodium sulfate, the solvent was evaporated in vacuo to
give a residue. The residue was purified by column chromatography
(SiO2; n-hexane/ethyl acetate¼4/1) to afford 8 (297.0 mg, 90% yield)
as a pale yellow powder. Mp 175e176 ꢀC; IR (KBr) 1655, 1626, 1504,
850 cmꢁ1 1H NMR (400 MHz, DMSO-d6)
; d 10.53 (s, 1H, ArOH),
10.42 (s, 1H, ArOH), 8.77 (s, 1H), 8.56 (d, J¼8.8 Hz, 1H), 8.13 (d,
J¼8.8 Hz, 1H), 8.07 (s, 1H), 8.02 (d, J¼8.8 Hz, 1H), 7.64 (d, J¼8.8 Hz,
1H), 7.33 (dd, J¼8.8, 2.4 Hz, 1H), 7.30 (d, J¼2.4 Hz, 1H), 7.27 (d,
J¼2.4 Hz, 1H), 7.17 (dd, J¼8.8, 2.4 Hz, 1H); 13C NMR
(100 MHz, DMSO-d6)
d 176.1, 159.4, 158.5, 154.0, 152.2, 138.9, 138.5,
132.0, 127.3, 125.0, 125.0, 122.4, 121.7, 119.9, 119.4, 118.8, 117.1, 114.1,
111.5, 110.4, 107.5; MS (EIþ) m/z (rel int.) 328 (Mþ,14), 313 (29), 247
(20), 231 (50), 149 (100), 83 (37); HRMS (EIþ) calcd for C21H12O4
(Mþ): 328.0736. Found: 328.0738.
1469, 1423, 1358, 1080 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 8.89 (s,
1H), 8.63 (d, J¼8.8 Hz, 1H), 8.26 (d, J¼8.8 Hz, 1H), 8.01 (d, J¼8.8 Hz,
1H), 7.94 (s, 1H), 7.61 (d, J¼8.8 Hz,1H), 7.48 (d, J¼2.4 Hz,1H), 7.46 (d,
J¼2.4 Hz, 1H), 7.41 (dd, J¼8.8, 2.4 Hz, 1H), 7.25 (dd, J¼8.8, 2.4 Hz,
1H), 5.37 (s, 2H, eCH2OCH3), 5.37 (s, 2H, eCH2OCH3), 3.57 (s, 3H,
eCH2OCH3), 3.56 (s, 3H, eCH2OCH3); 13C NMR (100 MHz, CDCl3)
4.5.6. Compound 7f. Yield 74%; yellow powder; mp >300 ꢀC; IR
(KBr) 3114,1618,1473,1248, 858, 777, 733 cmꢁ1; 1H NMR (270 MHz,
d 177.2, 158.1, 157.3, 154.1, 152.4, 138.5, 137.8, 131.4, 127.5, 126.0,
DMSO-d6)
d
10.60 (s, 2H, ArOH), 8.84 (d, J¼8.6 Hz, 2H), 8.06 (d,
124.8, 122.6, 122.3, 119.9, 119.5, 119.1, 118.9, 115.3, 112.4, 110.4, 107.8,
94.3, 94.2, 56.3 (one peak overlapped); MS (EIþ) m/z (rel int.) 416
(Mþ, 100), 386 (7), 242 (7); HRMS (EIþ) calcd for C25H20O6 (Mþ):
416.1260. Found: 416.1266. Anal. Calcd for C25H20O6: C, 72.11; H,
4.84. Found: C, 71.85; H, 4.97.
J¼8.6 Hz, 2H), 7.74 (d, J¼8.6 Hz, 2H), 7.41 (dd, J¼8.6, 2.2 Hz, 2H), 7.37
(d, J¼2.2 Hz, 2H); 13C NMR (100 MHz, DMSO-d6)
d 175.0, 159.3,
153.0, 138.4, 124.9, 123.5, 121.3, 119.7, 117.3, 115.6, 110.3; MS (FABþ)
m/z (rel int.) 329 (MþHþ, 4), 279 (7), 241 (11), 207 (22), 185 (50),
149 (51), 115 (75), 93 (100), 75 (86), 57 (50); HRMS (FABþ) calcd for
C21H13O4 (MþHþ): 329.0814. Found: 329.0814.
4.7. Compound 9
4.5.7. Compound 7g. Yield 98%; yellow powder; 280 ꢀC (decomp.);
To a stirred solution of 8 (52.1 mg, 0.125 mmol) in dry THF
(2 ml), phenyllithium (1.15 M in cyclohexane/diethylether, 163 ml,
IR (KBr) 3398, 1618, 1473, 1396, 1238, 1194, 781 cmꢁ1
;
1H NMR
(400 MHz, DMSO-d6)
d
10.90 (br s, 1H, ArOH), 10.19 (s, 1H, ArOH),
0.188 mmol) was added dropwise at ꢁ78 ꢀC and stirred for 2 h. The
reaction mixture was poured into the mixed solvent of ethyl acetate
and 0.1 M aq HCl. The organic layer was separated and washed
successively with water and brine. After dried over sodium sulfate,
the solvent was evaporated in vacuo to give a residue. The residue
was purified by column chromatography (SiO2; n-hexane/ethyl
acetate¼5/1) to afford 9 (60.6 mg, 98% yield) as a black oil. IR (film)
9.41 (d, J¼2.4 Hz, 1H), 8.18 (d, J¼8.8 Hz, 1H), 8.11 (d, J¼8.8 Hz, 1H),
7.90 (d, J¼8.8 Hz, 1H), 7.42 (d, J¼8.8 Hz, 1H), 7.14 (dd, J¼8.8, 2.4 Hz,
1H), 6.94 (dd, J¼8.8, 2.4 Hz, 1H), 6.91 (d, J¼2.4 Hz, 1H); 13C
NMR (100 MHz, DMSO-d6)
d 176.9, 163.3, 159.1, 157.9, 156.2, 136.5,
132.7, 130.6, 128.1, 124.5, 117.6, 115.9, 114.5, 114.4, 112.6, 109.4, 101.8;
MS (FABþ) m/z (rel int.) 279 (MþHþ, 21), 241 (16),185 (56),149 (53),

E. Azuma et al. / Tetrahedron 69 (2013) 1694e1699
1699
3444, 1637, 1608, 1412, 1352, 1252, 1149, 1078, 1001, 752 cmꢁ1
;
1H
8.51 (d, J¼9.2 Hz, 1H), 7.88 (s, 1H), 7.68 (s,
calcd for C25H22O5 (Mþ): 402.1467. Found: 402.1470. Anal. Calcd for
C25H22O5: C, 74.61; H, 5.51. Found: C, 74.47; H, 5.50.
NMR (400 MHz, CDCl3)
d
1H), 7.65 (d, J¼9.2 Hz, 1H), 7.47e7.45 (m, 2H), 7.40e7.34 (m, 5H),
7.28e7.25 (m, 2H), 7.17 (dd, J¼7.2, 7.2 Hz,1H), 7.07 (dd, J¼9.2, 2.4 Hz,
1H), 5.31 (s, 2H, eCH2OCH3), 5.30 (s, 2H, eCH2OCH3), 3.53 (s, 3H,
eCH2OCH3), 3.52 (s, 3H, eCH2OCH3); 13C NMR (100 MHz, CDCl3)
Acknowledgements
We appreciate the help received from Ms. Akiko Fujihashi (ICR,
Kyoto University) and Ms. Mayumi Shikata (VL, Kyoto Institute of
Technology) with the mass spectral analyses, and Ms. Toshiko
Hirano (ICR, Kyoto University) with the elemental analyses. This
study was partly supported by JSPS KAKENHI (No. 22390003),
Kyoto Prefectural University Research Fund, A-STEP from JST (No.
231Z03077), and a Grant-in-Aid for JSPS Fellows to E.A.
d
156.0, 155.7, 148.4, 145.0, 135.2, 134.7, 129.7, 128.8, 128.0, 127.4,
126.6, 126.6, 126.1, 126.0, 123.8, 122.2, 119.4, 119.3, 118.7, 118.0, 111.0,
110.0, 108.3, 94.4, 94.3, 70.8, 56.1 (four peaks overlapped); MS (EIþ)
m/z (rel int.) 494 (Mþ, 0.5), 477 (100), 401 (35); HRMS (EIþ) calcd for
C31H26O6 (Mþ): 494.1729. Found: 494.1715.
4.8. Compound 10
Supplementary data
To a stirred solution of methyltriphenylphosphonium bromide
(128.7 mg, 0.36 mmol) in dry toluene (6 ml), a solution of n-BuLi
(1.57 M n-hexane solution; 236 ml, 0.37 mmol) was added drop-
Supplementary data related to this article can be found online at
http://dx.doi.org/10.1016/j.tet.2012.12.035.
wise at ꢁ78 ꢀC. The resultant solution was allowed to warm to 0 ꢀC
with stirring for 50 min. A solution of 8 in dry toluene (4 ml) was
added dropwise at ꢁ78 ꢀC. The reaction mixture was stirred at
room temperature for 2 h and at 40 ꢀC for 2 h. The reaction mixture
was poured into the mixed solvent of ethyl acetate and 0.1 M aq
HCl. The organic layer was successively washed with water and
brine, dried over Na2SO4, filtered, and concentrated under reduced
pressure to dryness. The residue was purified by column chro-
matography (SiO2; n-hexane/EtOAc¼5/1) to afford 10 (14.1 mg,
47% yield) as a yellow oil. Compound 10 was gradually decom-
posed in a solution state. IR (film) 2927, 1631, 1506, 1392, 1252,
References and notes
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Suphavanich, K.; Maitarad, P.; Hannongbua, S.; Sudta, P.; Suksamrarn, S.; Tan-
tirungrotechai, Y.; Limtrakul, J. Monatsh. Chem. 2009, 140, 273.
3. (a) Kolokythas, G.; Kostakis, I. K.; Pouli, N.; Marakos, P.; Skaltsounis, A.-L.;
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Chen, W.-H.; Wang, B.; Xu, Z.-L. Bioorg. Med. Chem. 2006, 14, 5683.
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Strongin, R. M. J. Am. Chem. Soc. 2006, 128, 14081; (c) Yang, Y. J.; Lowry, M.; Xu,
X. Y.; Escobedo, J. O.; Sibrian-Vazquez, M.; Wong, L.; Schowalter, C. M.; Jensen,
T. J.; Fronczek, F. R.; Warner, I. M.; Strongin, R. M. Proc. Natl. Acad. Sci. U.S.A.
2008, 105, 8829; (d) Kim, S. H.; Gunther, J. R.; Katzenellenbogen, J. A. Org. Lett.
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Zhao, J.; Yue, D.; Campo, M. A.; Larock, R. C. J. Am. Chem. Soc. 2007, 129, 5288.
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Ed. 2012, 51, 5204.
7. Barbero, N.; SanMartin, R.; Domínguez, E. Green Chem. 2009, 11, 830.
8. (a) Davies, J. S. H.; Scheinmann, F.; Suschitzky, H. J. Org. Chem. 1958, 23, 307; (b)
Shi, J.; Zhang, X.; Neckers, D. C. J. Org. Chem. 1992, 57, 4418; (c) Chen, C.-A.; Yeh,
R.-H.; Lawrence, D. S. J. Am. Chem. Soc. 2002, 124, 3840.
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Hamada, M.; Iikubo, K.; Ishikawa, Y.; Ikeda, A.; Umezawa, K.; Nishiyama, S.
Bioorg. Med. Chem. Lett. 2003, 13, 3151.
1149, 1076, 1003 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 8.42 (d,
J¼8.8 Hz, 1H), 8.21 (s, 1H), 7.79 (d, J¼8.8 Hz, 1H), 7.77 (d, J¼8.8 Hz,
1H), 7.61 (s, 1H), 7.48 (d, J¼8.8 Hz, 1H), 7.39 (d, J¼2.4 Hz, 1H), 7.32
(d, J¼2.4 Hz, 1H), 7.31 (dd, J¼8.8, 2.4 Hz, 1H), 7.14 (dd, J¼8.8, 2.4 Hz,
1H), 5.75 (s, 1H, ]CH2), 5.62 (s, 1H, ]CH2), 5.33 (s, 2H, eCH2OCH3),
5.32 (s, 2H, eCH2OCH3), 3.55 (s, 3H, eCH2OCH3), 3.55 (s, 3H,
eCH2OCH3); 13C NMR (100 MHz, CDCl3)
d 156.1, 155.8, 149.4, 145.8,
135.5, 135.3, 132.8, 129.8, 126.6, 124.0, 122.8, 122.1, 122.0, 120.4,
120.1, 118.7, 118.3, 113.9, 111.8, 110.1, 108.4, 101.0, 94.4, 56.2 (two
peaks overlapped); MS (EIþ) m/z (rel int.) 414 (Mþ, 2), 279 (38), 167
(36), 149 (100); HRMS (EIþ) calcd for C26H22O5 (Mþ): 414.1467.
Found: 414.1463.
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Lett. 2007, 9, 3741; (b) Vandana, T.; Prasad, K. J. R. Indian J. Chem., Sect. B 2005,
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4.9. Compound 11
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To a stirred solution of 8 (40 mg, 0.096 mmol) in dry THF (4 ml),
a solution of boraneeTHF complex (1.1 M THF solution; 700
ml,
0.77 mmol) was added at 0 ꢀC. The resultant solution was allowed
to warm to room temperature for 5 h. The reaction mixture was
poured into the mixed solvent of ethyl acetate and water. The or-
ganic layer was successively washed with water and brine, dried
over Na2SO4, filtered, and concentrated under reduced pressure to
dryness. The residue was purified by column chromatography
(SiO2; n-hexane/EtOAc¼4/1) to afford 11 (25.2 mg, 65% yield) as
a white powder. Mp 153.0e155.0 ꢀC; IR (KBr) 1641, 1610, 1508, 1427,
13. Tanima, D.; Imamura, Y.; Kawabata, T.; Tsubaki, K. Org. Biomol. Chem. 2009, 7,
4689.
14. Azuma, E.; Nakamura, N.; Kuramochi, K.; Sasamori, T.; Tokitoh, N.; Sagami, I.;
Tsubaki, K. J. Org. Chem. 2012, 77, 3492.
15. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.;
Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Na-
katsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng,
G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.;
Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery,
J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K.
N.; Staroverov, V. N.; Keith, T.; Kobayashi, R.; Normand, J.; Raghavachari, K.;
Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J.
M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.;
Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.;
Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.;
Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.; Foresman,
J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, Revision B.01; Gaussian:
Wallingford CT, 2010.
1244, 1146, 1082, 1018, 876, 822 cmꢁ1 1H NMR (400 MHz, CDCl3)
;
d
8.37 (d, J¼8.8 Hz, 1H), 7.68 (d, J¼8.8 Hz, 1H), 7.63 (s, 1H), 7.53 (s,
1H), 7.43 (d, J¼8.8 Hz, 1H), 7.38 (d, J¼2.4 Hz, 1H), 7.34 (d, J¼2.4 Hz,
1H), 7.29 (dd, J¼8.8, 2.4 Hz, 1H), 7.25 (d, J¼8.8 Hz, 1H), 7.11 (dd,
J¼8.8, 2.4 Hz, 1H), 5.31 (s, 2H, eCH2OCH3), 5.30 (s, 2H, eCH2OCH3),
4.30 (s, 2H, ArCH2Ar), 3.54 (s, 3H, eCH2OCH3), 3.54 (s, 3H,
eCH2OCH3); 13C NMR (100 MHz, CDCl3)
d 155.3, 155.3, 150.8, 146.7,
134.6,134.4,128.8,127.4,127.3,126.6,123.1,121.5,120.2,120.2,118.7,
117.6, 112.7, 111.2, 109.9, 109.0, 94.6, 56.1, 28.1 (two peaks over-
lapped); MS (EIþ) m/z (rel int.) 462 (Mþ, 100), 357 (12); HRMS (EIþ)