Palladium(0)-catalyzed intramolecular heck reaction: A resourceful route for the synthesis of naphthoxepine naphthoxocine derivatives

Article abstract of DOI:10.1055/S-0029-1216984

The synthesis of oxocines and oxepines is difficult. Two efficient protocols have been developed for the construction of naphthoxepine and naphthoxocine derivatives by sequential Wittig olefination and intramolecular Heck reaction. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/S-0029-1216984

PAPER
3593
Palladium(0)-Catalyzed Intramolecular Heck Reaction: A Resourceful Route
for the Synthesis of Naphthoxepine and Naphthoxocine Derivatives
Synthesis of
Naph
.
thoxepine an
C
d Naphthoxocine
.DerivativesMajumdar,* Inul Ansary, Biswajit Sinha, Buddhadeb Chattopadhyay
Department of Chemistry, University of Kalyani, Kalyani 741235, India
E-mail: kcm_ku@yahoo.co.in
Received 25 May 2009; revised 19 June 2009
represents some naturally occurring oxepine and oxocine
derivatives.
Abstract: The synthesis of oxocines and oxepines is difficult. Two
efficient protocols have been developed for the construction of
naphthoxepine and naphthoxocine derivatives by sequential Wittig
olefination and intramolecular Heck reaction.
O
Cl
HO
Key words: Wittig olefination, oxepines, oxocines, Heck cycliza-
tion, palladium catalysis
HO
O
O
OH
Cl
pterulinic acid (1)
heliannuol B (2)
A number of medium-sized heterocyclic rings form part
of the structures of a range of biologically active natural
products1 and medicinally important compounds.2 Owing
to this and other reasons, over the last few years several
methodologies have been developed3 for the construction
of such ring systems. Enthalpic and entropic factors4 have
made the construction of medium-sized rings much more
difficult. Generally, most of the classical cyclization strat-
egies are often hampered by entropic factors and transan-
nular interactions.5 In particular, relatively fewer methods
based on cyclization or cycloaddition have been
implemented6 for the synthesis of medium-ring heterocy-
clic compounds from acyclic starting materials, although
these have been extensively used for the synthesis of reg-
ular heterocyclic systems. Therefore, the development of
new synthetic protocols for the synthesis of medium-ring
heterocyclic compounds remains a challenge.
OH
O
Ph
O
O
pterulone B (4)
redulanin A (3)
OH
HO
O
O
helianane (5)
heliannuol H (6)
MeN
O
Oxepines and oxocines are important structural units
present in numerous biologically active molecules and
have attracted considerable attention during the last few
years. Beside this, benzo-fused oxepine and oxocine de-
rivatives belong to a class of medicinally important com-
O
O
7
8
Figure 1 Some of the important naturally occurring bioactive oxo-
cines and oxepines
pounds. These
exhibit antianaphylactic,7 oral
hypotensive,8 and antiulcer properties. Moreover, benzox-
epine and -oxocine moieties are prevalent in many impor-
tant bioactive natural products such as radulanin,9
helianuols,10 and pterulone,11 as well as in some modern
pharmaceuticals with lipoxegenase inhibition activity.12
Therefore, the synthesis of these units carrying different
functionalities is important. Interestingly, despite their
broad spectrum of biological activity, benzo- and diben-
zo-fused oxepine and oxocine derivatives are not suffi-
ciently investigated, and one possible reason is the lack of
simple and straightforward synthetic procedures. Figure 1
Recently, we attempted13 to synthesize compounds 7 and
8 (Figure 1) by the application of the intramolecular Heck
reaction. For this purpose, we had chosen precursor 9a
with a vinyl group attached to the aromatic moiety, with
the expectation to achieve the exo-trig mode of Heck cy-
clization. However, 8-endo-trig cyclization occurred to
provide an efficient protocol for the construction of the
eight-membered ring system instead of the expected 7-
exo-trig cyclization by the intramolecular Heck reaction
from the vinylic precursors (Scheme 1).
These results encouraged us to continue further investiga-
tion to achieve a protocol for the preparation of the desired
products 7 and 8 via the exo-trig mode of cyclization.
Herein, we report our results.
SYNTHESIS 2009, No. 21, pp 3593–3602
x
x.
x
x
.
2
0
0
9
Advanced online publication: 28.08.2009
DOI: 10.1055/s-0029-1216984; Art ID: Z11009SS
© Georg Thieme Verlag Stuttgart · New York
It is remarkable to note that naphthoxepine derivatives
such as 7 and 82 (Figure 1) are used as antipsychotic drugs

3594
K. C. Majumdar et al.
PAPER
cently it has been reported17 that in the case of highly ac-
tivated double bonds, i.e., the Michael acceptor, the ring
formation become possible through the endo mode of cy-
clization. All these observations encouraged us to carry
out the palladium-catalyzed cyclization protocol for syn-
thesizing seven-membered oxepin derivatives, more pre-
cisely compounds 7 and 8 (Figure 1).
Br
O
Heck reaction
O
9a
10a
Scheme 1 Synthesis of oxocine via intramolecular Heck reaction
The required Heck precursors 9a–j for our investigation
were synthesized in 75–95% yields by Wittig reactions of
compounds 14a–j with methyltriphenylphosphonium io-
dide in anhydrous tetrahydrofuran in the presence of n-bu-
tyllithium at 0 °C to room temperature for about one hour
(Scheme 3). Compounds 14a–j, in turn, were prepared in
almost quantitative yields by the reactions of 1-formyl-2-
naphthol (12a) or 2-formylphenols 12b–f with either 2-
bromobenzyl bromide (13a) or 2-bromo-5-methoxyben-
zyl bromide (13b) in anhydrous acetone in the presence of
anhydrous potassium carbonate and a small amount of so-
dium iodide18 (Scheme 3). 1-Formyl-2-naphthol (12a)
was prepared by our recently developed protocol.13
essentially free of extrapyramidal symptoms and can be
administered in nontoxic effective quantities of active in-
gredients to animals.
The synthetic procedure3 for compounds 7 and 8 is quite
complicated. They were synthesized from a complex
starting material, 2-(2-carboxybenzyloxy)naphthalene,
and a number of reaction sequences were carried out to
furnish compounds 7 and 8.
The retrosynthetic analysis of compound 7 is summarized
in Scheme 2. The carbonyl functionality of 7 could arise
from simple ozonolysis or periodic acid oxidation of the
corresponding exo-methylene function. Construction of
the seven-membered ring may be accomplished by in-
tramolecular Heck reaction via an exo-trig mode of cy-
clization. The vinyl fragment may be incorporated by
Wittig olefination from the corresponding aldehydic com-
pound. This compound may be prepared by simple ben-
zylation of 1-formyl-2-naphthol. Naphthol is easily
formylated by various reported protocols.
When the intramolecular Heck reaction was performed
with the precursor 9b in the presence of palladium(II)
acetate as catalyst, potassium acetate as base, tetrabutyl-
ammonium bromide as additive,19 and in anhydrous N,N-
dimethylformamide as solvent at 100 °C for 3.5 hours un-
der a nitrogen atmosphere, to our utter frustration only
eight-membered naphthoxocine derivative 10b was
formed exclusively (67%) without even a trace of the de-
sired seven-membered naphthoxepine derivative 15b of
the corresponding biaryl product 16 (Scheme 4).
With our interest in synthesizing medium-sized heterocy-
clic compounds,14 we have devised an approach for the
construction of the important oxepine and oxocine deriv-
atives employing the Wittig reaction followed by a
regioselective intramolecular Heck reaction. We have en-
visioned that this route would not only lead to the naph-
thoxepine and naphthoxocine derivatives, but also to a va-
riety of new analogues possessing modifications around
the aryl ring.
Therefore, the reaction conditions were optimized by
changing the solvent, the base, and the temperature, and it
was found that in all the cases either the yield of the oxo-
cine derivative decreased or the starting material re-
mained completely unchanged. Changing the catalyst did
not cause any significant change in the outcome of the re-
action. The results are presented in Table 1.
Moreover, we recently reported20 the synthesis of differ-
ent oxathiocine derivatives starting from 17 containing
the vinylic counterpart, and, again, only eight-membered
oxathiocine derivatives such as 18 were isolated in good
to excellent yields through endo attack at the double bond
(Scheme 5).
The synthesis of heterocyclic compounds by the applica-
tion of a palladium-catalyzed intramolecular Heck reac-
tion has been extensively studied in our laboratory during
the last few years.15 A thorough search of the literature re-
vealed that in the case of small- to medium-ring syntheses,
the aryl–palladium complex follows an exo mode of cy-
clization, whereas in the case of large-ring syntheses
(~20), the endo mode becomes favorable.16 Moreover, re-
O
Br
O
O
O
7
Br
CHO
CHO
Br
OH
OH
+
Br
O
Scheme 2 Retrosynthetic analysis of compound 7
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Synthesis of Naphthoxepine and Naphthoxocine Derivatives
3595
Br
Table 1 Optimization of the Conditions for the Heck Reactiona
CHO
OH
OH
Br
ii
R1
i
Br
O
+
11a
12a
13a,b
O
9a
10a
Solvent
DMF
DMF
Br
Br
CHO
iii
O
R1
Entry
1b
2
Catalyst
Base
Yield (%)
86
O
R1
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(PPh3)4
Pd(PPh3)2Cl2
PdCl2
KOAc
Et3N
14a,b
9a,b
<5
3
K2CO3
Ag2CO3
Cs2CO3
KOAc
KOAc
KOAc
KOAc
Et3N
DMF
63
Br
R2
R2
CHO
OH
4
DMF
NRc
NRc
43
i
Br
ii
R1
+
OH
5
DMF
11b–f
12b–f
13a,b
6b
7b
8b
9
DMF
DMF
21
R2
CHO
O
R2
iii
Br
Br
DMF
36
O
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
DMF
NRc
NRc
NRc
<5
9c–j
14c–j
10
11
12
13
Et3N
R1
R1
R1 = H, OMe
2 = H, Me, OMe, 4-Cl-3-Me, t-Bu
Et3N
MeCN
dioxane
dioxane
R
Et3N
Scheme 3 Reagents and conditions: (i) aq NaOH, CHCl3, reflux, 4
h; (ii) acetone, K2CO3, NaI, 3–4 h; (iii) MePPh3I, n-BuLi, THF, 0 °C
to r.t.
KOAc
<5
a Reagents and conditions: 9a (1 equiv), base (2.75 equiv), cat. (10
mol%), solvent, 100 °C, 4 h.
b In these cases, TBAB was used as additive.
c NR = no reaction.
OMe
along with the contamination of the eight-membered
naphthoxocine derivative 10a in 13% yield (Table 2).
This observation led us to search for optimized conditions
for the formation of the desired compound 15a. It was
found that changing the base to potassium acetate or cesi-
um carbonate either increases the amount of 15a with al-
most disappearance of 10a, or no reaction occurred. On
the other hand, changing the solvent to N,N-dimethylfor-
mamide or dimethylacetamide (DMA) resulted in almost
all the starting material remaining unchanged, with the
formation of a trace amount of 10a. The amount of cata-
lyst played a crucial role in our investigation. A 5 mol%
of tetrakis(triphenylphosphine)palladium was found to be
ineffective for the reaction, whereas 20 mol% tetra-
kis(triphenylphosphine)palladium yielded product 15a in
satisfactory yield. On the basis of our observation, the op-
timized conditions for the reaction consist of the use of
tetrakis(triphenylphosphine)palladium and triethylamine
in acetonitrile at reflux for 24 hours, and the results are
summarized in Table 2.
O
Br
15b
O
OMe
Heck reaction
OMe
O
9b
10b
O
16
OMe
Scheme 4 Intramolecular Heck reaction of 9b
All these failures inspired us to make an all-out effort to
construct the desired seven-membered naphthoxepine 7
by a thorough and constant experimental manipulation.
When the Heck precursor 9a was allowed to react with 20
mol% tetrakis(triphenylphosphine)palladium as catalyst
and anhydrous triethylamine as base in refluxing acetoni-
trile for 24 hours, the required seven-membered naph-
thoxepine 15a was isolated in moderate yields (65%)
Similarly, all the Heck precursors 9b–j were treated under
the optimized conditions, and the results are summarized
in Table 3.
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K. C. Majumdar et al.
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Br
O
S
Heck reaction
O
O
S
S
O
O
O
O
O
O
17
18 observed
19 not observed
Scheme 5 Synthesis of oxathiocine derivatives
Table 2 Screening of the Heck Conditions
Br
O
Heck reaction
+
O
O
9a
15a (major)
10a (minor)
Entry
Amount Pd(PPh3)4 (mol%)
Base
Solvent
MeCN
MeCN
DMF
Yield of 15a (%)
Yield of 10a (%)
1
2
3
4
5
5
Et3N
–
–
20
20
20
20
Et3N
Et3N
65
–
13
10
43
–
KOAc
KOAc
DMF
–
DMF
–
Table 3 Summarized Results of the Heck Reactions under Optimized Conditions
Entry
Starting material
Product (major)
Time (h)
Yield (%)
exo
endo
Br
O
O
O
1
22
65
60
13
O
9a
9b
9b
9c
9c
15a
Br
Br
OMe
2
24
3.5
5
16
67
68
OMe
OMe
O
15b
3a
trace
trace
OMe
O
10b
Br
Br
O
O
4a
OMe
OMe
OMe
O
10c
OMe
5
26
67
11
O
15c
Synthesis 2009, No. 21, 3593–3602 © Thieme Stuttgart · New York

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Synthesis of Naphthoxepine and Naphthoxocine Derivatives
3597
Table 3 Summarized Results of the Heck Reactions under Optimized Conditions (continued)
Entry
Starting material
Product (major)
Time (h)
Yield (%)
exo
endo
Br
O
6a
4
–
–
71
O
10d
9d
Br
Me
O
O
7a
4
76
70
69
66
65
O
Me
10e
9e
Br
Me
8a
5
–
–
–
–
OMe
OMe
O
Me
10f
9f
Br
MeO
O
9a
5
O
MeO
10g
9g
Br
MeO
O
10a
3.5
OMe
OMe
O
MeO
10h
9h
Br
t-Bu
O
11a
4
OMe
OMe
O
t-Bu
10i
9i
Br
Cl
O
12a
5
–
60
Me
O
Cl
10j
Me
9j
a TBAB was used as additive.
Thus, we have demonstrated a synthetic strategy for the atives in very good yields via sequential Wittig olefination
preparation of naphthoxepin derivatives via a Wittig ole- and phosphine-free intramolecular Heck reaction.
fination and intramolecular Heck reaction protocol. The
product 15a can be easily transformed into compound 7
Melting points were determined of samples in an open capillary and
by simple ozonolysis or sodium periodate oxidation. The
antipsychotic activity of compounds 7 or 8 is well known
and it has been used recently as a drug for animals. Hence
its analogues may also be potentially bioactive.
are uncorrected. IR spectra of samples on KBr disks were recorded
1
on a Perkin-Elmer L 120-000A spectrometer. H NMR and 13C
NMR spectra were recorded on a Bruker DPX-300 and Bruker
DPX-400 spectrometer; samples were prepared as solns in CDCl3
with TMS as internal standard. CHN elemental analyses were re-
corded on a Perkin-Elmer 2400 series II CHN analyzer. Silica gel
(60–120 mesh, Spectrochem, India) was used for chromatographic
In conclusion, we have developed an easy protocol for the
formation of both seven-membered benzo- and naphthox-
epine derivatives in an exo-trig mode of cyclization as separation. Silica gel G (Spectrochem, India) was used for TLC. PE
refers to the fraction boiling in the range 60–80 °C.
well as eight-membered benzo- and naphthoxocine deriv-
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3598
K. C. Majumdar et al.
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Aldehyde 12a; Typical Procedure for the Preparation of Com-
pounds 12a–e by the Reimer–Tiemann Reaction
Anal. Calcd for C15H13BrO3: C, 56.10; H, 4.08. Found: C, 56.19; H,
3.99.
CHCl3 (16 mL) was added dropwise to a soln of 2-naphthol (11a;
14 g, 0.1 mol) and NaOH (32 g, 0.8 mol) in H2O (40 mL) at ca.
70 °C. The reaction mixture was allowed to stir for another 1 h at
the same temperature and subsequently allowed to cool. It was then
transferred to a 500-mL beaker with hot H2O and subsequently acid-
ified with 10 N H2SO4. This mixture was extracted with CH2Cl2
(3 × 75 mL), washed with H2O (2 × 50 mL), and dried (Na2SO4).
The organic layer was collected and the solvent was removed by
distillation. The crude material was purified by column chromatog-
raphy (silica gel, PE); this afforded product 12a. Compounds 12b–e
were prepared similarly.
Compound 14d
Yield: 96%; solid; mp 75–76 °C.
IR (KBr): 1670, 2850, 2923 cm–1.
1H NMR (400 MHz, CDCl3): d = 5.23 (s, 2 H, OCH2), 6.91–6.94
(m, 2 H, ArH), 7.11 (dd, J = 7.6, 1.5 Hz, 1 H, ArH), 7.15–7.17 (m,
3 H, ArH), 7.47 (dd, J = 8.6, 1.5 Hz, 1 H, ArH), 7.81 (dd, J = 7.4,
1.2 Hz, 1 H, ArH).
MS (EI, 70 eV): m/z = 290 [M+], 292 [M+ + 2].
Anal. Calcd for C14H11BrO2: C, 57.76; H, 3.81. Found: C, 57.85; H,
3.92.
2-Bromobenzyl 2-Formylaryl Ether 14b; Typical Procedure for
the Preparation of Compounds 14a–j
Compound 14e
Yield: 96%; solid; mp 41–42 °C.
IR (KBr): 1673, 2851, 2920 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.31 (s, 3 H, CH3), 5.21 (s, 2 H,
OCH2), 6.93 (d, J = 8.4 Hz, 1 H, ArH), 7.21 (d, J = 7.4 Hz, 1 H,
ArH), 7.32–7.36 (m, 2 H, ArH), 7.53 (d, J = 7.5 Hz, 1 H, ArH), 7.59
(d, J = 7.8 Hz, 1 H, ArH), 7.65 (d, J = 1.6 Hz, 1 H, ArH), 10.55 (s,
1 H, CHO).
A mixture of 1-formyl-2-naphthol (12a; 1.0 g, 5.81 mmol) and 2-
bromo-5-methoxybenzyl bromide (13b; 1.63 g, 5.81 mmol) in an-
hyd acetone (75 mL) was refluxed for 3–4 h in the presence of an-
hyd K2CO3 and NaI. After cooling, the reaction mixture was filtered
and the solvent was removed. The residual mass was extracted with
CH2Cl2 (3 × 30 mL), washed with H2O (2 × 40 mL) followed by
brine (40 mL), and dried (Na2SO4). Removal of CH2Cl2 gave a
crude product, which was chromatographed (silica gel, EtOAc–PE,
2:98); this gave compound 14b. The other compounds 14a,c–j were
prepared similarly.
MS (EI, 70 eV): m/z = 304 [M+], 306 [M+ + 2].
Anal. Calcd for C15H13BrO2: C, 59.04; H, 4.29. Found: C, 59.31; H,
4.43.
Compound 14a
Yield: 91%; solid; mp 131–132 °C.
IR (KBr): 1666, 2850, 2920 cm–1.
Compound 14f
Yield: 91%; solid; mp 97–98 °C.
IR (KBr): 1685, 2850, 2921 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.31 (s, 3 H, CH3), 3.78 (s, 3 H,
OCH3), 5.16 (s, 2 H, OCH2), 6.75 (dd, J = 8.7, 3.0 Hz, 1 H, ArH),
6.93 (d, J = 8.4 Hz, 1 H, ArH), 7.11 (d, J = 3.1 Hz, 1 H, ArH), 7.34
(dd, J = 8.6, 2.2 Hz, 1 H, ArH), 7.46 (d, J = 8.8 Hz, 1 H, ArH), 7.65
(d, J = 2.2 Hz, 1 H, ArH), 10.54 (s, 1 H, CHO).
1H NMR (400 MHz, CDCl3): d = 5.39 (s, 2 H, OCH2), 7.22 (dd,
J = 7.6, 1.6 Hz, 1 H, ArH), 7.33–7.37 (m, 2 H, ArH), 7.42 (dt,
J = 6.9, 1.0 Hz, 1 H, ArH), 7.55 (dd, J = 8.9, 1.2 Hz, 1 H, ArH),
7.61–7.65 (m, 2 H, ArH), 7.78 (d, J = 8.1 Hz, 1 H, ArH), 8.05 (d,
J = 9.2 Hz, 1 H, ArH), 9.28 (d, J = 8.7 Hz, 1 H, ArH), 11.01 (s, 1 H,
CHO).
MS (EI, 70 eV): m/z = 340 [M+], 342 [M+ + 2].
MS (EI, 70 eV): m/z = 334 [M+], 336 [M+ + 2].
Anal. Calcd for C18H13BrO2: C, 63.36; H, 3.84. Found: C, 63.41; H,
3.89.
Anal. Calcd for C16H15BrO3: C, 57.33; H, 4.51. Found: C, 57.58; H,
4.69.
Compound 14b
Yield: 89%; solid; mp 92–93 °C.
Compound 14g
IR (KBr): 1671, 2850, 2920 cm–1.
Yield: 93%; solid; mp 77–78 °C.
IR (KBr): 1685, 2850, 2920 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.76 (s, 3 H, OCH3), 5.22 (s, 2 H,
OCH2), 6.74 (dd, J = 8.9, 3.1 Hz, 1 H, ArH), 6.83 (d, J = 8.9 Hz, 1
H, ArH), 7.08 (d, J = 3.0 Hz, 1 H, ArH), 7.19 (dt, J = 7.7, 1.6 Hz, 1
H, ArH), 7.32 (dt, J = 7.7, 1.0 Hz, 1 H, ArH), 7.44 (d, J = 7.6 Hz, 1
H, ArH), 7.59 (dd, J = 8.6, 1.0 Hz, 1 H, ArH), 10.56 (s, 1 H, CHO).
1H NMR (400 MHz, CDCl3): d = 3.77 (s, 3 H, OCH3), 5.34 (s, 2 H,
OCH2), 6.77 (dd, J = 8.8, 3.0 Hz, 1 H, ArH), 7.10 (d, J = 2.9 Hz, 1
H, ArH), 7.31 (d, J = 9.0 Hz, 1 H, ArH), 7.43 (t, J = 7.3 Hz, 1 H,
ArH), 7.49 (d, J = 8.8 Hz, 1 H, ArH), 7.63 (t, J = 7.2 Hz, 1 H, ArH),
7.78 (d, J = 8.1 Hz, 1 H, ArH), 8.04 (d, J = 9.0 Hz, 1 H, ArH), 9.27
(d, J = 8.7 Hz, 1 H, ArH), 11.01 (s, 1 H, CHO).
MS (EI, 70 eV): m/z = 370 [M+], 372 [M+ + 2].
MS (EI, 70 eV): m/z = 320 [M+], 322 [M+ + 2].
Anal. Calcd for C19H15BrO3: C, 61.47; H, 4.07. Found: C, 61.39; H,
3.97.
Anal. Calcd for C15H13BrO3: C, 56.10; H, 4.08. Found: C, 56.31; H,
4.01.
Compound 14c
Yield: 96%; solid; mp 79–80 °C.
Compound 14h
Yield: 87%; solid; mp 74–75 °C.
IR (KBr): 1671, 2850, 2921 cm–1.
IR (KBr): 1678, 2850, 2921 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.79 (s, 3 H, OCH3), 5.20 (s, 2 H,
OCH2), 6.76 (dd, J = 8.8, 3.0 Hz, 1 H, ArH), 7.04 (d, J = 8.6 Hz, 1
H, ArH), 7.08 (d, J = 7.6 Hz, 1 H, ArH), 7.13 (d, J = 2.9 Hz, 1 H,
ArH), 7.47 (d, 1 H, J = 8.8 Hz, ArH), 7.54 (dt, J = 8.6, 3.0 Hz, 1 H,
ArH), 7.86 (dd, J = 7.6, 1.6 Hz, 1 H, ArH), 10.57 (s, 1 H, CHO).
1H NMR (400 MHz, CDCl3): d = 3.78 (s, 3 H, OCH3), 3.80 (s, 3 H,
OCH3), 5.15 (s, 2 H, OCH2), 6.76 (dd, J = 8.8, 3.0 Hz, 1 H, ArH),
6.99 (d, J = 9.0 Hz, 1 H, ArH), 7.08 (d, J = 3.0 Hz, 1 H, ArH), 7.12
(dd, J = 8.9, 3.0 Hz, 1 H, ArH), 7.35 (d, J = 3.0 Hz, 1 H, ArH), 7.46
(d, J = 8.8 Hz, 1 H, ArH), 10.54 (s, 1 H, CHO).
MS (EI, 70 eV): m/z = 320 [M+], 322 [M+ + 2].
MS (EI, 70 eV): m/z = 350 [M+], 352 [M+ + 2].
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Synthesis of Naphthoxepine and Naphthoxocine Derivatives
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Anal. Calcd for C16H15BrO4: C, 54.72; H, 4.31. Found: C, 54.81; H,
4.44.
ArH), 7.12–7.22 (m, 3 H, ArH), 7.45 (d, J = 8.8 Hz, 1 H, ArH), 7.50
(dd, J = 7.6, 1.6 Hz, 1 H, ArH).
MS (EI, 70 eV): m/z = 318 [M+], 320 [M+ + 2].
Compound 14i
Yield: 89%; solid; mp 80–81 °C.
IR (KBr): 1680, 2850, 2923 cm–1.
Anal. Calcd for C16H15BrO2: C, 60.21; H, 4.74. Found: C, 60.33; H,
4.67.
1H NMR (400 MHz, CDCl3): d = 1.35 (s, 9 H, C(CH3)3) 3.81 (s, 3
H, OCH3), 5.16 (s, 2 H, OCH2), 6.74 (dd, J = 8.7, 3.0 Hz, 1 H, ArH),
6.95 (d, J = 8.6 Hz, 1 H, ArH), 7.10 (d, J = 3.1 Hz, 1 H, ArH), 7.34
(dd, J = 8.6, 2.9 Hz, 1 H, ArH), 7.45 (d, J = 8.7 Hz, 1 H, ArH), 7.67
(d, J = 2.2 Hz, 1 H, ArH), 10.56 (s, 1 H, CHO).
Compound 9d
Yield: 88%; solid; mp 42–43 °C.
IR (KBr): 2851, 2922 cm–1.
1H NMR (400 MHz, CDCl3): d = 5.18 (s, 2 H, OCH2), 5.29 (dd,
J = 11.2, 1.2 Hz, 1 H, =CHaHb), 5.74 (dd, J = 17.6, 1.2 Hz, 1
H, =CHaHb), 6.76 (dd, J = 8.8, 3.0 Hz, 1 H, CH2=CH), 6.91–6.94
(m, 2 H, ArH), 7.16–7.21 (m, 2 H, ArH), 7.32 (dd, J = 7.4, 1.6 Hz,
1 H, ArH), 7.51–7.59 (m, 3 H, ArH).
MS (EI, 70 eV): m/z = 376 [M+], 378 [M+ + 2].
Anal. Calcd for C19H21BrO3: C, 60.49; H, 5.61. Found: C, 60.67; H,
5.60.
MS (EI, 70 eV): m/z = 288 [M+], 290 [M+ + 2].
Compound 14j
Yield: 90%; solid; mp 128–129 °C.
IR (KBr): 1679, 2852, 2922 cm–1.
Anal. Calcd for C15H13BrO: C, 62.30; H, 4.53. Found: C, 62.17; H,
4.43.
1H NMR (300 MHz, CDCl3): d = 2.42 (s, 3 H, CH3), 5.21 (s, 2 H,
OCH2), 6.86 (d, J = 9.0 Hz, 2 H, ArH), 6.94 (s, 1 H, ArH), 7.35 (t,
J = 6.9 Hz, 2 H, ArH), 7.81 (s, 1 H, ArH), 10.69 (s, 1 H, CHO).
Compound 9e
Yield: 94%; viscous liquid.
IR (neat): 2849, 2921 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.32 (s, 3 H, CH3), 5.12 (s, 2 H,
OCH2), 5.26 (dd, J = 11.2, 1.4 Hz, 1 H, =CHaHb), 5.75 (dd,
J = 17.7, 1.4 Hz, 1 H, =CHaHb), 6.80 (d, J = 8.3 Hz, 1 H, ArH), 7.01
(dd, J = 8.3, 2.0 Hz, 1 H, CH2=CH), 7.10–7.19 (m, 2 H, ArH), 7.34
(dt, J = 7.5, 1.0 Hz, 2 H, ArH), 7.56 (dt, J = 7.8, 1.0 Hz, 2 H, ArH).
MS (EI, 70 eV): m/z = 338 [M+], 340 [M+ + 2].
Anal. Calcd for C15H12BrClO2: C, 53.05; H, 3.56. Found: C, 53.26;
H, 3.33.
2-Bromobenzyl 2-Vinylaryl Ether 9b; Typical Procedure for
the Synthesis of Compounds 9b–j by Wittig Olefination Reac-
tion
MS (EI, 70 eV): m/z = 302 [M+], 304 [M+ + 2].
Anal. Calcd for C16H15BrO: C, 63.38; H, 4.99. Found: C, 63.57; H,
5.13.
The Wittig salt MePPh3I (1.63 g, 4.03 mmol) in anhyd THF (20 mL)
was placed in a 25-mL round-bottom flask. A 1.6 M soln of n-BuLi
in hexane (2.5 mL, 4.0 mmol) was added at 0 °C under a N2 atmo-
sphere. Compound 14b (1.0 g, 2.69 mmol) in anhyd THF (5 mL)
was added to the reaction mixture at 0 °C. Stirring was continued
for 1 h at r.t. The THF was removed under reduced pressure and aq
NH4Cl (5 mL) was added. This mixture was extracted with CH2Cl2
(3 × 30 mL), washed with H2O (2 × 20 mL), and dried (Na2SO4).
CH2Cl2 was removed by distillation and the crude product was pu-
rified by column chromatography (silica gel, EtOAc–PE, 2:98); this
gave 9b. Compounds 9a,c–j were obtained similarly. Compound 9a
has been reported previously.13
Compound 9f
Yield: 87%; solid; mp 57–58 °C.
IR (KBr): 2850, 2920 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.29 (s, 3 H, CH3), 3.77 (s, 3 H,
OCH3), 5.07 (s, 2 H, OCH2), 5.26 (dd, J = 11.2, 1.2 Hz, 1
H, =CHaHb), 5.74 (dd, J = 17.7, 1.2 Hz, 1 H, =CHaHb), 6.72 (dd,
J = 8.7, 3.0 Hz, 1 H, CH2=CH), 6.80 (d, J = 8.3 Hz, 1 H, ArH), 7.01
(dd, J = 8.3, 1.6 Hz, 1 H, ArH), 7.09–7.16 (m, 2 H, ArH), 7.31 (d,
J = 1.4 Hz, 1 H, ArH), 7.44 (d, J = 8.7 Hz, 1 H, ArH).
MS (EI, 70 eV): m/z = 332 [M+], 334 [M+ + 2].
Compound 9b
Yield: 91%; solid; mp 72–73 °C.
IR (KBr): 2851, 2919 cm–1.
Anal. Calcd for C17H17BrO2: C, 61.28; H, 5.14. Found: C, 61.13; H,
4.99.
1H NMR (400 MHz, CDCl3): d = 3.77 (s, 3 H, OCH3), 5.22 (s, 2 H,
OCH2), 5.77 (dd, J = 11.2, 2.0 Hz, 1 H, =CHaHb), 5.81 (dd,
J = 17.7, 2.0 Hz, 1 H, =CHaHb), 6.73 (dd, J = 8.7, 3.0 Hz, 1 H,
CH2=CH), 7.13–7.23 (m, 2 H, ArH), 7.27 (d, J = 9.0 Hz, 1 H, ArH),
7.36 (dt, J = 7.8, 1.0 Hz, 1 H, ArH), 7.44–7.48 (m, 2 H, ArH), 7.75
(d, J = 9.0 Hz, 1 H, ArH), 7.78 (d, J = 8.2 Hz, 1 H, ArH), 8.18 (d,
J = 8.5 Hz, 1 H, ArH).
Compound 9g
Yield: 90%; viscous liquid.
IR (neat): 2851, 2922 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.78 (s, 3 H, OCH3), 5.08 (s, 2 H,
OCH2), 5.28 (dd, J = 11.2, 1.2 Hz, 1 H, =CHaHb), 5.74 (dd,
J = 17.6, 1.2 Hz, 1 H, =CHaHb), 6.76 (dd, J = 8.9, 3.0 Hz, 1 H,
CH2=CH), 6.84 (d, J = 8.9 Hz, 1 H, ArH), 7.06 (d, J = 3.0 Hz, 1 H,
ArH), 7.09–7.19 (m, 2 H, ArH), 7.33 (dt, J = 7.7, 1.0 Hz, 1 H, ArH),
7.57 (dt, J = 7.7, 1.0 Hz, 2 H, ArH).
MS (EI, 70 eV): m/z = 368 [M+], 370 [M+ + 2].
Anal. Calcd for C20H17BrO2: C, 65.05; H, 4.64. Found: C, 65.16; H,
4.59.
MS (EI, 70 eV): m/z = 318 [M+], 320 [M+ + 2].
Compound 9c
Yield: 89%; solid; mp 55–56 °C.
IR (KBr): 2850, 2921 cm–1.
Anal. Calcd for C16H15BrO2: C, 60.21; H, 4.74. Found: C, 59.97; H,
4.81.
Compound 9h
Yield: 95%; viscous liquid.
IR (neat): 2850, 2919 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.77 (s, 3 H, OCH3), 5.11 (s, 2 H,
OCH2), 5.28 (dd, J = 11.2, 1.4 Hz, 1 H, =CHaHb), 5.75 (dd,
J = 17.6, 1.4 Hz, 1 H, =CHaHb), 6.74 (dd, J = 8.7, 3.0 Hz, 1 H,
CH2=CH), 6.90 (d, J = 8.3 Hz, 1 H, ArH), 6.96 (t, J = 7.6 Hz, 1 H,
Synthesis 2009, No. 21, 3593–3602 © Thieme Stuttgart · New York

3600
K. C. Majumdar et al.
PAPER
1H NMR (400 MHz, CDCl3): d = 3.77 (s, 6 H, OCH3), 5.04 (s, 2 H,
OCH2), 5.28 (dd, J = 11.2, 1.0 Hz, 1 H, =CHaHb), 5.74 (dd,
J = 17.6, 1.0 Hz, 1 H, =CHaHb), 6.71–6.77 (m, 2 H, CH2=CH, ArH),
6.84 (d, J = 8.9 Hz, 1 H, ArH), 7.05 (d, J = 3.0 Hz, 1 H, ArH), 7.07–
7.16 (m, 2 H, ArH), 7.43 (d, J = 8.7 Hz, 1 H, ArH).
Anal. Calcd for C20H16O2: C, 83.31; H, 5.59. Found: C, 83.11; H,
5.72.
Compound 10c
Yield: 68%; solid; mp 69–70 °C.
MS (EI, 70 eV): m/z = 348 [M+], 350 [M+ + 2].
IR (KBr): 2852, 2921 cm–1.
Anal. Calcd for C17H17BrO3: C, 58.47; H, 4.91. Found: C, 58.53; H,
5.01.
1H NMR (400 MHz, CDCl3): d = 3.81 (s, 3 H, OCH3), 5.11 (s, 2 H,
OCH2), 6.40 (d, J = 13.8 Hz, 1 H, =CHaHb), 6.51 (d, J = 13.8 Hz, 1
H, =CHaHb), 6.86 (dd, J = 8.4, 2.6 Hz, 1 H, ArH), 6.91 (d, J = 2.5
Hz, 1 H, ArH), 6.95 (d, J = 7.5 Hz, 1 H, ArH), 6.98 (d, J = 7.6 Hz,
1 H, ArH), 7.07 (dt, J = 8.2, 1.4 Hz, 1 H, ArH), 7.21 (t, J = 8.2 Hz,
1 H, ArH), 7.23 (s, 1 H, ArH).
13C NMR (75 MHz, CDCl3): d = 55.4, 74.6, 114.4, 114.9, 120.9,
122.3, 126.3, 127.6, 127.9, 128.2, 131.1, 133.2, 135.2, 136.8, 158.7,
158.9.
Compound 9i
Yield: 90%; viscous liquid.
IR (neat): 2851, 2924 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.32 (s, 9 H, C(CH3)3), 3.78 (s, 3
H, OCH3), 5.09 (s, 2 H, OCH2), 5.28 (d, J = 10.8 Hz, 1 H, =CHaHb),
5.77 (d, J = 17.7 Hz, 1 H, =CHaHb), 6.74 (d, J = 7.2 Hz, 1 H, ArH),
6.85 (d, J = 8.4 Hz, 1 H, ArH), 7.13 (m, 2 H, CH2=CH and ArH
overlapped), 7.24 (d, J = 7.5 Hz, 1 H, ArH), 7.45 (d, J = 8.7 Hz, 1
H, ArH), 7.52 (s, 1 H, ArH).
MS (EI, 70 eV): m/z = 238 [M+].
Anal. Calcd for C16H14O2: C, 80.65; H, 5.92. Found: C, 80.89; H,
6.01.
MS (EI, 70 eV): m/z = 374 [M+], 376 [M+ + 2].
Compound 10d
Yield: 71%; solid; mp 81–82 °C.
IR (KBr): 2851, 2921 cm–1.
Anal. Calcd for C20H23BrO2: C, 64.01; H, 6.18. Found: C, 63.89; H,
6.20.
Compound 9j
Yield: 75%; solid, mp 48–49 °C.
IR (KBr): 2850, 2922 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.34 (s, 3 H, CH3), 5.10 (s, 2 H,
OCH2), 5.27 (d, J = 10.8 Hz, 1 H, =CHaHb), 5.71 (s, J = 17.7 Hz, 1
H, =CHaHb), 6.91 (m, 2 H, CH2=CH and ArH overlapped), 7.10 (s,
1 H, ArH), 7.22–7.27 (m, 2 H, ArH), 7.33 (dt, J = 7.8, 1.0 Hz, 1 H,
ArH), 7.54 (dt, J = 7.7, 1.0 Hz, 1 H, ArH).
1H NMR (400 MHz, CDCl3): d = 5.09 (s, 2 H, OCH2), 6.47 (d,
J = 13.8 Hz, 1 H, =CHaHb), 6.59 (d, J = 13.8 Hz, 1 H, =CHaHb),
6.92–6.93 (m, 3 H, ArH), 7.18–7.23 (m, 2 H, ArH), 7.51–7.61 (m,
3 H, ArH).
13C NMR (100 MHz, CDCl3): d = 74.1, 120.9, 122.1, 125.7, 127.6,
128.1, 128.6, 128.8, 129.9, 130.0, 131.5, 135.3, 135.4, 138.6, 158.7.
MS (EI, 70 eV): m/z = 208 [M+].
Anal. Calcd for C15H12O: C, 86.51; H, 5.81. Found: C, 86.34; H,
6.03.
MS (EI, 70 eV): m/z = 336 [M+], 338 [M+ + 2].
Anal. Calcd for C16H14BrClO: C, 56.92; H, 4.18. Found: C, 56.75;
H, 3.88.
Compound 10e
Yield: 76%; solid; mp 71–72 °C.
Naphthoxocine 10b; Typical Procedure for the Synthesis of
Compounds 10b–j by the Heck Reaction
IR (KBr): 2852, 2922 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.25 (s, 3 H, CH3), 5.14 (s, 2 H,
OCH2), 6.47 (d, J = 13.8 Hz, 1 H, =CHaHb), 6.57 (d, J = 13.8 Hz, 1
H, =CHaHb), 6.89 (dd, J = 6.0, 1.6 Hz, 2 H, ArH), 7.00 (s, 1 H,
ArH), 7.24–7.36 (m, 4 H, ArH).
13C NMR (75 MHz, CDCl3): d = 20.3, 74.4, 120.7, 125.5, 127.5,
128.1, 128.6, 129.2, 129.7, 129.8, 131.3, 131.5, 135.5, 135.5, 138.5,
156.6.
A mixture of 9b (200 mg, 0.54 mmol), TBAB (210 mg, 0.65 mmol)
and anhyd KOAc (145 mg, 1.48 mmol) was taken up in anhyd DMF
(10 mL) under a N2 atmosphere. Pd(OAc)2 (12 mg, 10 mol%) was
added and the mixture was stirred on an oil bath at 100 °C for ca. 4
h. The reaction mixture was cooled, H2O (10 mL) was added, and
the mixture was extracted with EtOAc (3 × 30 mL) and washed with
H2O (2 × 25 mL), followed by brine (30 mL). The organic layer was
dried (Na2SO4), and the solvent was removed by distillation to fur-
nish a viscous mass, which was purified by column chromatography
(silica gel, EtOAc–PE, 1:99); this afforded product 10b. The other
substrates 9c–j were similarly treated to give the corresponding
products 10c–j. Compound 10a has been reported previously.13
MS (EI, 70 eV): m/z = 222 [M+].
Anal. Calcd for C16H14O: C, 86.45; H, 6.35. Found: C, 86.19; H,
6.31.
Compound 10f
Yield: 70%; solid; mp 57–58 °C.
Compound 10b
Yield: 67%; solid; mp 77–78 °C.
IR (KBr): 2851, 2923 cm–1.
IR (KBr): 2851, 2922 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.25 (s, 3 H, CH3), 3.82 (s, 3 H,
OCH3), 5.08 (s, 2 H, OCH2), 6.35 (d, J = 13.8 Hz, 1 H, =CHaHb),
6.51 (d, J = 13.8 Hz, 1 H, =CHaHb), 6.84–6.89 (m, 4 H, ArH), 7.00
(s, 1 H, ArH), 7.22 (d, J = 8.4 Hz, 1 H, ArH).
13C NMR (100 MHz, CDCl3): d = 20.4, 55.4, 74.9, 114.3, 114.8,
120.7, 126.2, 127.6, 127.9, 128.9, 131.1, 131.6, 133.3, 135.4, 137.0,
156.7, 158.9.
1H NMR (400 MHz, CDCl3): d = 3.75 (s, 3 H, OCH3), 5.43 (s, 2 H,
OCH2), 6.94 (d, J = 13.8 Hz, 1 H, =CHaHb), 7.13 (d, J = 13.8 Hz, 1
H, =CHaHb), 7.33 (d, J = 6.9 Hz, 1 H, ArH), 7.34 (dd, J = 6.0, 1.9
Hz, 1 H, ArH), 7.36–7.38 (m, 2 H, ArH), 7.42–7.44 (m, 2 H, ArH),
7.49 (d, J = 8.5 Hz, 1 H, ArH), 7.63 (dd, J = 8.8, 2.8 Hz, 1 H, ArH),
7.91 (d, J = 8.4 Hz, 1 H, ArH).
13C NMR (75 MHz, CDCl3): d = 55.2, 74.5, 113.6, 113.8, 121.2,
121.7, 124.0, 124.2, 125.7, 126.2, 128.1, 129.1, 129.9, 130.7, 131.1,
131.2, 133.2, 136.5, 153.1, 158.4.
MS (EI, 70 eV): m/z = 252 [M+].
Anal. Calcd for C17H16O2: C, 80.93; H, 6.39. Found: C, 81.03; H,
6.55.
MS (EI, 70 eV): m/z = 288 [M+].
Synthesis 2009, No. 21, 3593–3602 © Thieme Stuttgart · New York

PAPER
Synthesis of Naphthoxepine and Naphthoxocine Derivatives
3601
Compound 10g
Yield: 69%; solid; mp 74–75 °C.
IR (KBr): 2851, 2924 cm–1.
Naphthoxepines 15a–c by Heck Reaction; General Procedure
A mixture of 9a (200 mg, 0.59 mmol) and anhyd Et3N (2 mL) was
taken up in anhyd MeCN (10 mL) under a N2 atmosphere.
Pd(PPh3)4 (136 mg, 20 mol%) was added and the mixture was
stirred on an oil bath under reflux for ca. 24 h. The progress of the
reaction was monitored by TLC. The reaction mixture was cooled,
H2O (10 mL) was added, and the mixture was extracted with EtOAc
(3 × 30 mL) and washed with H2O (2 × 30 mL), followed by brine
(30 mL). The organic layer was dried (Na2SO4). The solvent was re-
moved by distillation to furnish a viscous mass, which was purified
by column chromatography (silica gel, EtOAc–PE, 1:99); this af-
forded the product 15a. The other substrates 9b,c were similarly
treated to give products 15b,c.
1H NMR (400 MHz, CDCl3): d = 3.80 (s, 3 H, OCH3), 5.10 (s, 2 H,
OCH2), 6.42 (d, J = 13.8 Hz, 1 H, =CHaHb), 6.63 (d, J = 13.8 Hz, 1
H, =CHaHb), 6.88 (dd, J = 7.1, 3.1 Hz, 1 H, ArH), 7.05 (s, 1 H,
ArH), 7.32 (dd, J = 6.9, 1.7 Hz, 1 H, ArH), 7.34–7.39 (m, 4 H,
ArH).
13C NMR (100 MHz, CDCl3): d = 55.7, 75.4, 114.4, 119.0, 121.7,
127.4, 127.6, 128.6, 129.0, 129.2, 129.6, 132.0, 135.9, 138.2, 153.1,
154.6.
MS (EI, 70 eV): m/z = 238 [M+].
Anal. Calcd for C16H14O2: C, 80.65; H, 5.92. Found: C, 80.58; H,
6.07.
Compound 15a
Yield: 65%; gummy.
IR (neat): 2873, 2927 cm–1.
Compound 10h
1H NMR (400 MHz, CDCl3): d = 5.36 (s, 2 H, OCH2), 5.61 (s, 1
H, =CHaHb), 5.90 (s, 1 H, =CHaHb), 7.00–7.15 (m, 2 H, ArH), 7.30–
7.36 (m, 3 H, ArH), 7.45 (t, J = 7.16 Hz, 1 H, ArH), 7.53 (d, J = 7.24
Hz, 1 H, ArH), 7.68 (d, J = 8.8 Hz, 1 H, ArH), 7.75 (d, J = 7.96 Hz,
1 H, ArH), 8.34 (d, J = 8.56 Hz, 1 H, ArH).
13C NMR (75 MHz, CDCl3): d = 71.7, 114.9, 120.8, 120.9, 123.6,
123.9, 124.0, 124.9, 125.0, 126.2, 126.4, 127.2, 127.8, 128.2, 128.5,
129.4, 131.7, 137.2, 153.3.
Yield: 66%; solid; mp 67–68 °C.
IR (KBr): 2849, 2919 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.76 (s, 3 H, OCH3), 3.82 (s, 3 H,
OCH3), 5.04 (s, 2 H, OCH2), 6.33 (d, J = 13.8 Hz, 1 H, =CHaHb),
6.55 (d, J = 13.8 Hz, 1 H, =CHaHb), 6.66 (dd, J = 8.7, 3.1 Hz, 1 H,
ArH), 6.73 (d, J = 3.1 Hz, 1 H, ArH), 6.85 (dd, J = 7.9, 2.8 Hz, 2 H,
ArH), 6.94 (d, J = 8.7 Hz, 1 H, ArH), 7.22 (s, 1 H, ArH).
13C NMR (100 MHz, CDCl3): d = 55.2, 55.7, 74.5, 114.3, 114.7,
119.5, 125.7, 126.2, 128.1, 128.2, 131.1, 131.2, 131.5, 133.2, 136.5,
154.0, 158.4.
MS (EI, 70 eV): m/z = 281 [M+ + Na].
Anal. Calcd for C19H14O: C, 88.34; H, 5.46. Found: C, 88.28; H,
5.72.
MS (EI, 70 eV): m/z = 268 [M+].
Anal. Calcd for C17H16O3: C, 76.10; H, 6.01. Found: C, 76.19; H,
5.91.
Compound 15b
Yield: 60%; gummy.
IR (neat): 2853, 2926 cm–1.
Compound 10i
1H NMR (300 MHz, CDCl3): d = 3.78 (s, 3 H, OCH3), 5.44 (s, 2 H,
OCH2), 6.75 (d, J = 2.4 Hz, 1 H, =CHaHb), 6.78 (d, J = 2.7 Hz, 1
H, =CHaHb), 6.95 (m, 2 H, ArH), 7.14 (d, J = 8.4 Hz, 1 H, ArH),
7.20 (d, J = 9.0 Hz, 1 H, ArH), 7.34 (t, J = 7.2 Hz, 1 H, ArH), 7.45
(t, J = 7.8 Hz, 1 H, ArH), 7.63 (d, J = 9.0 Hz, 1 H, ArH), 7.72 (d,
J = 8.1 Hz, 1 H, ArH), 7.92 (d, J = 8.4 Hz, 1 H, ArH).
13C NMR (100 MHz, CDCl3): d = 54.1, 70.0, 111.5, 112.3, 113.9,
118.3, 119.8, 121.0, 122.6, 123.3, 125.4, 127.2, 127.7, 128.4, 128.5,
129.3, 131.4, 137.9, 152.3, 158.7.
Yield: 65%; solid; mp 69–70 °C.
IR (KBr): 2850, 2921 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.29 (s, 9 H, C(CH3)3), 3.83 (s, 3
H, OCH3), 5.12 (s, 2 H, OCH2), 6.46 (d, J = 13.8 Hz, 2 H, CH =CH),
6.86–6.94 (m, 3 H, ArH), 7.11 (d, J = 8.1 Hz, 1 H, ArH), 7.18–7.25
(m, 2 H, ArH).
13C NMR (100 MHz, CDCl3): d = 31.4, 34.0, 55.4, 74.4, 114.3,
114.9, 120.3, 125.3, 125.4, 127.5, 128.3, 131.2, 131.9, 133.1, 137.0,
144.8, 156.4, 158.8.
MS (EI, 70 eV): m/z = 288 [M+].
MS (EI, 70 eV): m/z = 294 [M+].
Anal. Calcd for C20H16O2: C, 83.31; H, 5.59. Found: C, 83.02; H,
5.61.
Anal. Calcd for C20H22O2: C, 81.60; H, 7.53. Found: C, 81.73; H,
7.51.
Compound 15c
Yield: 67%; gummy.
Compound 10j
Yield: 60%; solid; mp 88–89 °C.
IR (KBr): 2852, 2922 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.26 (s, 3 H, CH3), 5.16 (s, 2 H,
OCH2), 6.40 (d, J = 13.5 Hz, 1 H, CHa=CHb), 6.56 (d, J = 13.5 Hz,
1 H, CHa=CHb), 6.84 (s, 1 H, ArH), 7.15 (s, 1 H, ArH), 7.26–7.38
(m, 4 H, ArH).
IR (neat): 2852, 2922 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.81 (s, 3 H, OCH3), 5.12 (s, 2 H,
OCH2), 5.21 (s, 1 H, =CHaHb), 5.64 (s, 1 H, =CHaHb), 6.81–6.86
(m, 3 H, ArH), 6.90 (t, J = 7.2 Hz, 1 H, ArH), 7.13–7.17 (m, 1 H,
ArH), 7.28 (d, J = 8.04 Hz, 1 H, ArH), 7.42 (dd, J = 7.8, 1.16 Hz, 1
H, ArH).
13C NMR (100 MHz, CDCl3): d = 19.5, 73.8, 123.0, 124.6, 126.9,
127.8, 128.5, 128.6, 128.9, 130.0, 131.3, 134.5, 135.0, 136.3, 138.4,
156.6.
13C NMR (100 MHz, CDCl3): d = 55.3, 70.2, 112.5, 112.8, 113.4,
114.5, 119.5, 121.0, 126.6, 127.2, 128.9, 129.6, 133.2, 138.8, 155.9,
159.8.
MS (EI, 70 eV): m/z = 256 [M+].
MS (EI, 70 eV): m/z = 238 [M+].
Anal. Calcd For C16H13ClO: C, 74.85; H, 5.10. Found: C, 74.55; H,
4.98.
Anal. Calcd for C16H14O2: C, 80.65; H, 5.92. Found: C, 80.94; H,
6.07.
Synthesis 2009, No. 21, 3593–3602 © Thieme Stuttgart · New York

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K. C. Majumdar et al.
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