Substitution alters the mode of molecular iodine-mediated intramolecular cyclization: Syntheses of benzoxepine and benzo-2 H-pyran derivatives

Article abstract of DOI:10.1055/s-0030-1260196

The synthesis of benzoxepine and benzo-2H-pyran derivatives by the implementation of an inxepensive and easy to handle molecular iodine-mediated intramolecular electrophilic cyclization strategy is described. Simple substitution at the terminus of the pro

Full text of DOI:10.1055/s-0030-1260196

PAPER
3287
Substitution Alters the Mode of Molecular Iodine-Mediated Intramolecular
Cyclization: Syntheses of Benzoxepine and Benzo-2H-pyran Derivatives
B
enzoxepine and B
r
enzo-2
H
i
-pyran
s
Derivativ
h
es na C. Majumdar,*a,1 Inul Ansary,a Biswajit Sinha,a Brindaban Roy,a Balasubramanian Sridharb
a
Department of Chemistry, University of Kalyani, Kalyani 741235, West Bengal, India
Fax +91(33)25828282; E-mail: kcm_ku@yahoo.co.in
b
Laboratory of X-ray Crystallography, IICT, Hyderabad 500007, India
Received 25 June 2011; revised 27 July 2011
of well-established methodologies are available for the
construction of complex heterocyclic compounds.14 The
development of new and efficient approaches for their
syntheses, employing mild, economical, and high-yield-
ing routes, is an area of current research interest.15 Recent-
ly, the electrophilic cyclization of heteroatomic
nucleophiles, such as oxygen, nitrogen, and sulfur, with
alkynes has proven to be an effective method for the syn-
thesis of these types of heterocyclic compounds.16 Due to
the excellent alkynophilicity of molecular iodine, recent-
ly, much attention has been paid to iodine-based alkyne
activation for developing new and efficient iodocycliza-
tions.17,18 Moreover, transition-metal-catalyzed cycliza-
tions of polyunsaturated systems to give various
heterocyclic compounds containing seven-membered
rings have been developed,19 however, only a few suc-
cessful examples20 are found in the literature for the effec-
tive construction of medium-sized ring systems by iodine-
mediated reaction, possibly because of the disadvanta-
geous influence of both entropic and enthalpic factors, as
well as because of electronic and steric effects. Thus, the
development of a novel method for the annulation of
medium-ring heterocycles, ideally including metal-free,
mild, environmentally friendly, and atom-economic con-
ditions, is necessary. Larock et al.21 reported that an aryl
propargylic ether with the terminal of the propargylic
group protected, undergoes iodocyclization reaction to
give benzopyran derivatives F. Surprisingly, we recently
reported20 the syntheses of different benzoxepine deriva-
Abstract: The synthesis of benzoxepine and benzo-2H-pyran de-
rivatives by the implementation of an inxepensive and easy to han-
dle molecular iodine-mediated intramolecular electrophilic
cyclization strategy is described. Simple substitution at the terminus
of the propargyl group alters the course of the iodocyclization.
Key words: iodine, intramolecular cyclization, benzoxepine,
benzo-2H-pyrans
Substituted heterocyclic compounds are frequently found
as key structural components in a vast number of biologi-
cally active natural and non-natural compounds. Five- and
six-membered heterocyclic rings are important structural
subunits in numerous natural products, such as polyacety-
lenic esters,2 phytane-type diterpenedilactones,3 cylin-
driline C, and lepadiformine.4 The 2H-benzopyran
Daurichromenic acid is known to have anti-HIV
properties5 as well as antidiabetic activity.6 They are also
useful for the treatment of proliferative skin disorders, mi-
crobial infections,7 and show potent antifungal activity.8 It
was found that compound A is a selective rat 5-
hydroxytryptamine1B (r5-HT1B) receptor antagonist.9
Ishizuka et al. reported that 2-(benzo[1,3]dioxol-5-yl)-
2H-chromene-3-carboxylic acid (B), was found by modi-
fications of their own angiotensin II antagonist.10 On the
other hand, medium-ring oxygen heterocycles, especially
oxepines and oxocines, are important structural units that
are present in numerous biologically active molecules be-
longing to a class of medicinally important compounds.
These exhibit antianaphylactic, oral hypotensive, and an-
tiulcer activities.11 The fungal metabolites pterulone (C)
and its analogue D,12 which inhibit the eukaryotic respira-
tory chain at the NADH site of the ubiquinone oxi-
doreductase, possess potent antifungal activity, and are
only weakly cytotoxic. Similarly, pterulinic acid (E) ex-
hibits significant antifungal and either weak or no cyto-
toxic activity, and is an effective inhibitor of eukaryotic
respiration (Figure 1).13
O
O
N
O
H
N
A
COOH
O
O
O
Cl
O
B
For these and other reasons, the synthesis of various het-
erocycles, both regular- and medium-ring heterocycles,
has been a research objective for many groups for over a
century, and a search of the literature reveals that a variety
O
Cl
OH
pterulone (C)
Cl
O
pterulinic acid (E)
COOH
O
O
pterulone analogue (D)
SYNTHESIS 2011, No. 20, pp 3287–3296
x
x.
x
x
.
2
0
1
1
Advanced online publication: 01.09.2011
DOI: 10.1055/s-0030-1260196; Art ID: Z64011SS
Figure 1
© Georg Thieme Verlag Stuttgart · New York

3288
K. C. Majumdar et al.
PAPER
tives G by a 7-exo mode of cyclization without the forma- deshielding zone of the carbonyl oxygen of the COCH3
tion of any benzopyran derivatives (Figure 2).
group. The proposed seven-membered structure is also
supported by the observed resonance of two doublet pro-
tons that were observed at d = 3.43 (J = 1.6 Hz) and 4.49
(J = 1.6 Hz) ppm; in the case of an eight-membered ring,
the proton at d = ~ 4.49 ppm would be expected to split in
a more complex manner. The relative stereochemistry of
the iodine (methoxy) substituent and the ketone in the
benzoxepine moiety was found from an NOE experiment
to be in a syn configuration.20
I
O
O
H
R
I
I
Ar
O
F
G
Figure 2
To expand the scope of the iodine-mediated process, the
reaction was also carried out using the procedure stated
above but adding a small amount of methanol; under these
conditions, it was observed that the reaction produced a
reduced amount of diiodo product 4a and a small amount
of a new 7-exo cyclized product 7a. The presence of the
new product establishes the fact that, in this system, io-
dine acted as an electrophile and methanol as a nucleo-
phile. Encouraged by this positive result, a thorough
investigation was performed to find the optimum reaction
conditions. Interestingly, the amount of iodine as well as
base (NaHCO3) both played important roles in this reac-
tion. The use of two equivalents of iodine increased the
amount of the uncyclized iodo-derivative 5a at the ex-
pense of the desired cyclized product. A similar result was
These conflicting findings encouraged us to undertake a
thorough study on the effect of substituents upon the
mode of cyclization of our previously reported systems.
For this purpose, a number of substrates with either a pro-
tected or unprotected propargylic group were submitted to
the iodocyclization reaction conditions; herein, we report
the results.
The required precursors for our present study 3a–c were
synthesized in 68–78% yields by heating compounds 2a–
c to reflux with propargyl bromide in acetone in the pres-
ence of anhydrous K2CO3 and a catalytic amount of NaI.
Compounds 2a–c were, in turn, prepared by heating sali-
cylaldehydes 1a–c to reflux in ethyl methyl ketone in the
presence of anhydrous K2CO3. The hydroxy aldehydes
1a–c were prepared according to our earlier published
procedure (Scheme 1).22
Table 1 Optimization of I2-Mediated Reactions
O
I
MeO
O
O
O
H
O
H
R
CHO
R
R
(i)
(ii)
O
I
I
OH
O
O
4a
O
OH
3a–c
7a
3a
1a: R = H
1b: R = Me
1c: R = OMe
2a–c
Entry Electrophile Nucleophile Solvent Product Yield
(equiv)
I2 (1)
I2 (2)
I2 (3)
I2 (1)
I2 (1)
I2 (1)
I2 (1)
(equiv)
(%)b
Scheme 1 Reagents and conditions: (i) anhyd K2CO3, ethyl methyl
ketone, reflux, 10–12 h; (ii) propargyl bromide, anhyd K2CO3, anhyd
acetone, NaI, reflux, 5–6 h.
1a
2
–
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeOH
4a
4a
4a
55
–
20
When the iodocyclization reaction was performed with a
mixture of compound 3a, molecular iodine (1 equiv), and
NaHCO3 (1 equiv) at room temperature in anhydrous
acetonitrile solvent for eight hours, seven-membered
benzoxepine derivative 4a was formed in 55% yield by a
7-exo mode of cyclization, accompanied by the formation
of some uncyclized iodo-derivative 5a. The 8-endo cy-
clized product 6a was not obtained (Scheme 2). The struc-
tures of the cyclized products were determined from their
spectroscopic and analytical data. The high 1H NMR shift
value of the olefinic proton confirms that it is in the
3
–
15
4
MeOH (1)
MeOH (10)
MeOH (20)
MeOH
4a + 7a 25 + 10
4a + 7a 25 + 25
5
6a
7
7a
7a
50
45
a Optimized reaction conditions. In each case, 1 equiv of NaHCO3
was used as base.
b Isolated yield.
O
O
O
I
I
O
H
H
(i)
+
+
O
O
I
I
O
O
I
4a
7-exo (major)
5a
minor
6a
3a
8-endo (not found)
Scheme 2 Reagents and conditions: (i) I2, NaHCO3, anhyd MeCN, r.t.
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PAPER
Benzoxepine and Benzo-2H-pyran Derivatives
3289
obtained when two equivalents of NaHCO3 was used. In- mediated cyclization reaction. In our present investiga-
creasing the amount of both I2 and NaHCO3 drastically tion, we have also found that a similar type of reaction oc-
reduced the amount of cyclized product, and no improve- curs when the alkyl group of the keto alkyl moiety is
ment was observed when the reaction time was extended. substituted with different alkyl groups. This suggests that
In acetonitrile solvent, iodine acted both as an electrophile the alkyl group has no effect upon the mode of cyclization
and a nucleophile. It was also observed that increasing the of this reaction. However, it should be noted that com-
amount of methanol increased the amount of 7a formed. pound 3d, possessing an aryl group in place of an alkyl
When an excess of methanol was used (20 equiv) the re- group in the keto alkyl moiety, does not undergo the io-
action afforded only a mixture of 7a and uncyclized iodo- docyclization reaction, probably for electronic reasons.
derivative 5a, without any cyclized diiodo product 4a. We also carried out the reaction of compound 2a with one
The results are summarized in Table 1.
equivalent of iodine in acetonitrile, which resulted in the
formation of an inseparable mixture of products.
After establishing the optimized reaction conditions, other
substrates were similarly treated under the optimized re- We then turned our attention to extending the scope of this
action conditions to afford the corresponding exo-cy- methodology to the construction of oxygen heterocycles
clized benzoxepine derivatives in 48–52% yields; the by protecting the terminal position of the propargylic tri-
results are summarized in Table 2.
It is worth noting that we have recently reported20 the syn-
thesis of some benzoxepine derivatives by an iodine-
ple bond with aryl groups. For this purpose, a number of
starting materials 9a–f were synthesized in moderate to
good yields by the Sonogashira coupling reaction of 8a–d
and iodobenzene derivatives in the presence of
Table 2 Synthesis of Benzoxepine Derivatives
Entry
1
Starting
Product
Time (h)
Yield (%)
55
O
I
O
H
8
O
I
O
3a
3a
4a
O
MeO
O
H
2
3
4
8
6
7
50
52
48
O
I
O
7a
O
I
O
H
O
I
O
3b
4b
O
MeO
MeO
O
H
MeO
O
O
I
O
3c
7b
4c
5
6
12
12
NR
NR
O
O
3d
3d
O
7c
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3290
K. C. Majumdar et al.
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O
R1
O
O
R1
R1
(i)
(ii)
O
O
O
I
8a: R1 = H
9a: R1 = H, R2 = Me
9b: R1 = H, R2 = H
R2
R2
10a–f
8b: R1 = Me
8c: R1 = OMe
8d: R1 = t-Bu
9c: R1 = Me, R2 = H
9d: R1 = OMe, R2 = Me
9e: R1 = Me, R2 = OMe
9f: R1 = t-Bu, R2 = OMe
Scheme 3 Reagents and conditions: (i) para-substituted iodobenzene, [Pd(PPh3)2Cl2], CuI, DMF–Et3N, r.t.; (ii) I2, NaHCO3, MeCN, r.t.
[Pd(PPh3)2Cl2] as catalyst and copper(I) iodide as co-cat- the results are summarized in Table 3. With the optimized
alyst in anhydrous triethylamine and N,N-dimethylform- reaction conditions, the other substrates 9b–f were treated
amide (DMF) (1:4) as mixed solvent at room temperature similarly to afford the benzo-2H-pyran derivatives 10b–f
for five hours. When 9a was subjected to the intramolec- in 85–93% yields (Table 4).
ular iodocyclization reaction under the optimized reaction
conditions (Table 1), benzo-2H-pyran derivative 10a was
Table 3 Optimization of I2-Mediated Reactions
formed in only 25% yield, leaving the rest of the starting
Entry Electrophile Base
Solvent
Product Yield
(%)b
material unchanged in the reaction mixture (Scheme 3).
The expected benzoxepine derivative was not obtained at
all. The product 10a was characterized from its spectro-
scopic data and the configuration as well as the mode of
cyclization was confirmed by a single crystal X-ray dif-
fraction analysis (Figure 3).23
(equiv)
I2 (1)
I2 (2)
I2 (3)
I2 (3)
I2 (3)
I2 (3)
I2 (3)
(equiv)
1
2
3a
4
5
6
7
NaHCO3 (1)
NaHCO3 (2)
NaHCO3 (3)
K2CO3 (3)
MeCN
MeCN
MeCN
MeCN
CH2Cl2
MeCN
MeOH
10a
10a
10a
10a
10a
10a
10a
25
60
90
35
25
50
45
NaHCO3 (3)
Na2CO3 (3)
NaHCO3 (3)
a Optimized reaction conditions.
b Isolated yield.
The mechanism of the iodocyclization is assumed to pro-
ceed through initial formation of iodonium complex 11
(Scheme 4). When R1 = H, the remaining I– ion may at-
tack the double bond of 11 in a Michael fashion to form
carbanion 13. Subsequent attack of the carbanion at the io-
donium moiety in a 7-exo mode may afford the seven-
membered oxepine derivatives 4. However, when
R1 = aryl, the reaction sequence becomes completely dif-
ferent because the intermediate 13 formed suffers steric
hindrance between the more bulky aryl group and the car-
bonyl group of the a,b-unsaturated counterpart. It is as-
sumed that the initially formed iodonium intermediate 11
undergoes electrophilic attack by electron clouds of the
aromatic ring, followed by the loss of a proton through the
action of the base, giving the benzo-2H-pyran derivatives
10. The formation of 7a may be explained by the attack of
MeOH nucleophile at the b-carbon of the a,b-unsaturated
carbonyl part of the initially formed iodonium intermedi-
ate 11 in a Michael fashion, followed by abstraction of a
proton by the base (NaHCO3) to form the intermediate 17.
Finally, the benzoxepine derivative 7a is formed by the at-
Figure 3 ORTEP diagram of compound 10a
The formation of 10a indicates that, in the presence of a
terminal protecting group, the reaction does not occur be-
tween the a,b-unsaturated double bond and the O-propar-
gylated counterpart, whereas the double bond of the
benzene ring participates in the reaction to afford the
product. Therefore, a further optimization study was
needed to increase the yield of the new reaction. It was ob-
served that two equivalents of iodine, together with two
equivalents of NaHCO3 gave a better result (60% yield).
By varying the amounts of both iodine and base it was
found that use of three equivalents each of iodine and
NaHCO3 was optimum; under these conditions the yield
was dramatically increased to 90%. Of the bases tested,
NaHCO3 found to be most effective for bringing the reac-
tion to completion. It is interesting to note that methanol
does not participate in the reaction. On the basis of our ob-
servation, the optimized conditions for the reaction were
established [I2 (3 equiv), NaHCO3 (3 equiv), MeCN, r.t.];
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PAPER
Benzoxepine and Benzo-2H-pyran Derivatives
3291
tack of the carbanion on the iodonium moiety of interme- heterocycles, i.e., both benzoxepine- and benzo-2H-pyran
diate 17.
derivatives, with good to excellent yields under similar re-
action conditions, simply by modifying the terminal of the
triple bond.
From the above discussion it is clear that the iodine-medi-
ated cyclization protocol is very useful for the construc-
tion of a range of heterocycles in a straightforward way. In summary, we have developed an inexpensive, mild,
Furthermore, the presence of a halogen functionality on and easy to handle approach to the synthesis, from similar
the heterocyclic products makes them useful substrates substrates, of both benzoxepine- and 2H-pyrans, which
for derivatization, usually through metal-catalyzed C–C are more difficult to prepare using conventional methods.
bond formation.24 It is also important to note that we have The procedure reported here is more economical than oth-
selectively synthesized both six- and seven-membered er methods and avoids difficulties associated with product
Table 4 Synthesis of Benzo-2H-pyran Derivatives
Entry
Starting
Product
Time (h)
Yield (%)
O
O
1
8
90
O
O
I
10a
9a
O
O
2
3
4
8
7
7
85
93
88
O
O
I
10b
9b
O
O
O
O
I
10c
9c
O
MeO
MeO
O
O
O
I
10d
9d
9e
9f
O
O
5
6
92
O
O
MeO
I
OMe
10e
O
O
O
6
6
87
O
MeO
OMe
I
10f
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3292
K. C. Majumdar et al.
PAPER
I
O–
O
I–
O
R1
R1
R1
R3
R3
path a
R3
I2
R2
R2
O
O
O
I
12
R2
I
11
I
R3
R3
I
R3
I
O
H
R1
O
R1
7-exo
R1
R2
7-exo
O
R2 = H
R2
2
I
O
O
I
O
13
I
4 (observed)
14
R1
O
O
R1
R1
O
R3
R3
path b
6-endo
base
R3
O
O
11
H
R2
R2
O
R2
15
I
10 (observed)
I
I
R3
MeOH
OMe O–
OMe R3
MeO
O
path c
R1
O
R1
7-exo
R1
R1
R3
R2
MeOH
R3
O
R2
R2
base
R2
O
O
I
O
O
16
17
I
11
I
I
7a
R
R
R
1 = H, OMe
2 = H
3 = Et
Scheme 4 Proposed mechanism
chromatography (EtOAc–PE, 1:19) to give compound 3a as a col-
orless viscous gum. Compounds 3b and 3c were synthesized ac-
cordingly.
isolation. This methodology is tolerant toward a variety of
functional groups, including carbonyl groups, and pro-
vides a handle for further organic transformations. Further
investigations into the scope and limitations of this elec-
trophilic cyclization are underway.
Compound 3a
Yield: 75%; colorless viscous gum.
IR (neat): 1665, 2119, 3290 cm–1.
Melting points were determined in open capillaries and are uncor-
rected. IR spectra were recorded with a Perkin–Elmer L 120–000A
spectrometer (cm–1) on KBr disks. 1H and 13C NMR spectra were re-
corded with a Bruker DPX-400 spectrometer in CDCl3 with TMS as
internal standard. Mass spectra were recorded with a Qtof-Micro in-
strument. CHN was recorded with a 2400 series II CHN Perkin–
Elmer analyzer. Silica gel [60–120 mesh and 230–400 mesh; Spec-
trochem, India] were used for chromatographic separation. Silica
gel G and silica gel GF-254 (Spectrochem, India) were used for
TLC. Petroleum ether (PE) refers to the fraction boiling between
60–80 °C.
1H NMR (CDCl3, 400 MHz): d = 1.17 (t, J = 7.2 Hz, 3 H, CH2CH3),
2.54 (t, J = 2.4 Hz, 1 H, propargylic CH), 2.73 (q, J = 7.2 Hz, 2 H,
CH2CH3), 4.79 (d, J = 2.4 Hz, 2 H, OCH2), 6.78 (d, J = 16.4 Hz,
1 H, CHa=CHb), 7.02 (d, J = 7.6 Hz, 1 H, ArH), 7.06 (d, J = 8.0 Hz,
1 H, ArH), 7.35–7.39 (m, 1 H, ArH), 7.58 (d, J = 7.6 Hz, 1 H, ArH),
7.92 (d, J = 16.4 Hz, 1 H, CHa=CHb).
13C NMR (CDCl3, 125 MHz): d = 7.2, 30.9, 56.3, 75.9, 78.3, 112.4,
123.2, 125.3, 127.9, 128.7, 139.1, 144.5, 154.1, 199.3.
MS (ESI): m/z = 237 [M + Na]+.
Anal. Calcd for C14H14O2: C, 78.48; H, 6.59. Found: C, 78.42; H,
6.55.
Compounds 2a–c and 8a–d were obtained according to our previ-
ously published procedure.20
Compound 3b
Yield: 78%; colorless viscous gum.
Synthesis of Compounds 3a–c; Typical Procedure
A mixture of compound 2a (1.70 mmol) and propargyl bromide
(2.55 mmol) was heated at reflux in anhydrous acetone (30 mL) in
the presence of anhydrous K2CO3 (8.50 mmol) and a catalytic
amount NaI for 6 h. The reaction mixture was then cooled to r.t., fil-
tered, and the solvent was removed under reduced pressure. The
crude product was purified by silica gel (60–120 mesh) column
IR (neat): 1669, 2129, 3287 cm–1.
1H NMR (CDCl3, 400 MHz): d = 1.17 (t, J = 7.2 Hz, 3 H, CH2CH3),
2.31 (s, 3 H, CH3), 2.53 (t, J = 2.0 Hz, 1 H, propargylic CH), 2.72
(q, J = 7.2 Hz, 2 H, CH2CH3), 4.75 (d, J = 2.0 Hz, 2 H, OCH2), 6.76
(d, J = 16.4 Hz, 1 H, CHa=CHb), 6.95 (d, J = 8.4 Hz, 1 H, ArH),
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Benzoxepine and Benzo-2H-pyran Derivatives
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7.17 (d, J = 8.4 Hz, 1 H, ArH), 7.38 (s, 1 H, ArH), 7.89 (d,
J = 16.4 Hz, 1 H, CHa=CHb).
Anal. Calcd for C15H16I2O2: C, 37.37; H, 3.35. Found: C, 37.41; H,
3.47.
13C NMR (CDCl3, 100 MHz): d = 7.2, 20.6, 30.9, 56.7, 76.0, 78.5,
113.5, 123.6, 124.7, 127.9, 129.0, 139.3, 145.1, 154.7, 199.8.
Synthesis of Compounds 7a and 7b; Typical Procedure
A mixture of compound 3a (0.50 mmol), I2 (0.50 mmol), anhydrous
NaHCO3 (0.50 mmol), and anhydrous MeOH (10.00 mmol) was
stirred in anhydrous MeCN (5 mL) at r.t. for 8 h. The reaction mix-
ture was diluted to 50 mL with CH2Cl2 and the organic phase was
washed successively with 10% aqueous sodium thiosulfate (20
mL), H2O (20 mL), brine (20 mL), and dried over anhydrous
Na2SO4. The solvent was removed under reduced pressure and the
crude product was purified by silica gel (230–400 mesh) column
chromatography (EtOAc–PE, 3:97) to give compound 7a as a col-
orless gum. Compound 7b was synthesized accordingly.
MS (ESI): m/z = 251 [M + Na]+.
Anal. Calcd for C15H16O2: C, 78.92; H, 7.06. Found: C, 78.68; H,
7.23.
Compound 3c
Yield: 68%; colorless viscous gum.
IR (neat): 1668, 2120, 3269 cm–1.
1H NMR (CDCl3, 400 MHz): d = 1.18 (t, J = 7.2 Hz, 3 H, CH2CH3),
2.54 (t, J = 2.4 Hz, 1 H, propargylic CH), 2.74 (q, J = 7.2 Hz, 2 H,
CH2CH3), 3.79 (s, 3 H, OCH3), 4.73 (d, J = 2.4 Hz, 2 H, OCH2),
6.73 (d, J = 16.4 Hz, 1 H, CHa=CHb), 6.96 (dd, J = 8.4, 2.8 Hz, 1 H,
ArH), 7.06 (d, J = 8.4 Hz, 1 H, ArH), 7.11 (d, J = 2.8 Hz, 1 H,
ArH), 7.87 (d, J = 16.4 Hz, 1 H, CHa=CHb).
Compound 7a
Yield: 50%; colorless gum.
IR (neat): 1713, 2928, 3062 cm–1.
1H NMR (CDCl3, 400 MHz): d = 1.14 (t, J = 7.2 Hz, 3 H, CH2CH3),
2.79 (q, J = 7.2 Hz, 2 H, CH2CH3), 3.26 (s, 3 H, OCH3), 4.75 (d,
J = 2.2 Hz, 2 H, OCH2), 4.86 (d, J = 9.2 Hz, 1 H, CH), 5.23 (d,
J = 9.2 Hz, 1 H, CH), 6.87 (d, J = 8.0 Hz, 1 H, ArH), 7.06 (dd,
J = 7.6, 7.2 Hz, 1 H, ArH), 7.25 (d, J = 2.2 Hz, 1 H, =CHI), 7.32–
7.35 (m, 2 H, ArH).
13C NMR (CDCl3, 100 MHz): d = 8.2, 29.7, 55.3, 57.1, 76.3, 78.9,
115.4, 123.0, 124.3, 129.6, 132.7, 139.5, 151.5, 155.2, 199.2.
MS (ESI): m/z = 267 [M + Na]+.
Anal. Calcd for C15H16O3: C, 73.75; H, 6.60. Found: C, 73.79; H,
6.39.
13C NMR (CDCl3, 100 MHz): d = 8.3, 29.7, 32.9, 33.3, 58.2, 74.8,
82.0, 98.3, 112.3, 121.8, 124.5, 125.1, 129.8, 155.9, 205.9.
MS (ESI): m/z = 395 [M + Na]+.
Synthesis of Compounds 4a and 4b; Typical Procedure
A mixture of compound 3a (0.50 mmol), I2 (0.50 mmol), and anhy-
drous NaHCO3 (0.50 mmol) was stirred in anhydrous MeCN (5 mL)
at r.t. for 8 h. The reaction mixture was diluted to 50 mL with
CH2Cl2. The organic phase was washed successively with 10%
aqueous sodium thiosulfate (20 mL), H2O (20 mL), brine (20 mL),
and dried over anhydrous Na2SO4. The solvent was removed under
reduced pressure and the crude product was purified by silica gel
(230–400 mesh) column chromatography (EtOAc–PE, 3:97) to give
compound 4a as a colorless gum. Compound 4b was synthesized
accordingly.
Anal. Calcd for C15H17IO3: C, 48.40; H, 4.60. Found: C, 48.09; H,
4.47.
Compound 7b
Yield: 48%; colorless gum.
IR (neat): 1710, 2933, 3069 cm–1.
1H NMR (CDCl3, 400 MHz): d = 1.40 (t, J = 7.2 Hz, 3 H, CH2CH3),
2.79 (q, J = 7.2 Hz, 2 H, CH2CH3), 3.27 (s, 3 H, OCH3), 3.79 (s,
3 H, OCH3), 4.70 (s, 2 H, OCH2), 4.81 (d, J = 9.0 Hz, 1 H, CH),
5.20 (d, J = 9.0 Hz, 1 H, CH), 6.83–6.89 (m, 3 H, ArH), 7.23 (s,
1 H, =CHI).
13C NMR (CDCl3, 100 MHz): d = 8.3, 29.7, 32.8, 33.2, 55.7, 58.2,
75.6, 81.8, 98.7, 113.6, 114.1, 114.5, 128.1, 150.1, 154.5, 204.8.
Compound 4a
Yield: 55%; colorless gum.
IR (neat): 1710, 2926, 3065 cm–1.
1H NMR (CDCl3, 400 MHz): d = 1.12 (t, J = 7.2 Hz, 3 H, CH2CH3),
2.45–2.67 (m, 2 H, CH2CH3), 3.43 (d, J = 1.6 Hz, 1 H, CH), 4.49 (d,
J = 1.6 Hz, 1 H, CH), 4.71 (s, 2 H, OCH2), 6.84 (d, J = 7.8 Hz, 1 H,
ArH), 7.02 (dd, J = 7.8, 7.6 Hz, 1 H, ArH), 7.21 (m, 2 H, = CHI and
1 × ArH), 7.28–7.32 (m, 1 H, ArH).
MS (ESI): m/z = 425 [M + Na]+.
Anal. Calcd for C16H19IO4: C, 47.78; H, 4.76. Found: C, 47.71; H,
4.77.
13C NMR (CDCl3, 100 MHz): d = 7.2, 30.9, 54.4, 62.7, 74.5, 82.3,
98.2, 112.1, 121.9, 124.7, 125.3, 129.6, 155.7, 206.7.
Synthesis of Compounds 9a–f: Typical Procedure
A mixture of compound 8a (1.50 mmol), p-methyliodobenzene
(1.80 mmol), anhydrous Et3N (2 mL), [Pd(PPh3)2Cl2] (3 mol%), and
CuI (3 mol%) was stirred in anhydrous DMF (8 mL) at r.t. for 5 h.
The reaction mixture was diluted to 70 mL with CH2Cl2 and the or-
ganic phase was washed successively with H2O (3 × 25 mL), brine
(25 mL), and dried over anhydrous Na2SO4. The solvent was re-
moved under reduced pressure and the crude product was purified
by silica gel (60–120 mesh) column chromatography (EtOAc–PE,
1:19) to give compound 9a as a white solid. Compounds 9b–f were
synthesized accordingly.
MS (ESI): m/z = 507 [M + K]+.
Anal. Calcd for C14H14I2O2: C, 35.92; H, 3.01. Found: C, 35.75; H,
2.97.
Compound 4b
Yield: 52%; colorless gum.
IR (neat): 1715, 2927, 3068 cm–1.
1H NMR (CDCl3, 400 MHz): d = 1.12 (t, J = 7.2 Hz, 3 H, CH2CH3),
2.28 (s, 3 H, CH3), 2.45–2.62 (m, 2 H, CH2CH3), 3.43 (d,
J = 1.6 Hz, 1 H, CH), 4.47 (d, J = 1.6 Hz, 1 H, CH), 4.68 (s, 2 H,
OCH2), 6.74 (d, J = 8.4 Hz, 1 H, ArH), 6.98 (s, 1 H, ArH), 7.08 (d,
J = 8.4 Hz, 1 H, ArH), 7.19 (s, 1 H, =CHI).
13C NMR (CDCl3, 100 MHz): d = 7.2, 20.6, 30.9, 54.4, 62.7, 74.6,
82.1, 98.5, 112.3, 124.4, 125.8, 129.9, 131.4, 153.7, 206.7.
Compound 9a
Yield: 66%; white solid; mp 80–81 °C.
IR (KBr): 1668, 2235, 2927, 3054 cm–1.
1H NMR (CDCl3, 400 MHz): d = 2.34 (s, 3 H, CH3), 2.39 (s, 3 H,
CH3), 5.00 (s, 2 H, OCH2), 6.76 (d, J = 16.4 Hz, 1 H, CHa=CHb),
7.03 (m, 1 H, ArH), 7.11 (d, J = 7.8 Hz, 2 H, ArH), 7.15 (d, J =
8.0 Hz, 1 H, ArH), 7.31 (d, J = 7.8 Hz, 2 H, ArH), 7.39 (m, 1 H,
MS (ESI): m/z = 521 [M + K]+.
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ArH), 7.58 (d, J = 8.0 Hz, 1 H, ArH), 7.93 (d, J = 16.4 Hz, 1 H,
CHa=CHb).
13C NMR (CDCl3, 100 MHz): d = 21.5, 27.1, 57.2, 82.7, 87.9, 113.1,
118.9, 121.6, 124.0, 128.0, 128.2, 129.1, 131.7, 138.6, 139.1, 156.5,
199.2.
J = 16.4 Hz, 1 H, CHa=CHb), 6.82 (d, J = 8.8 Hz, 2 H, ArH), 7.04
(d, J = 8.4 Hz, 1 H, ArH), 7.19 (d, J = 8.4 Hz, 1 H, ArH), 7.36 (d,
J = 8.4 Hz, 2 H, ArH), 7.38 (s, 1 H, ArH), 7.91 (d, J = 16.4 Hz, 1 H,
CHa=CHb).
13C NMR (CDCl3, 100 MHz): d = 20.5, 27.1, 55.3, 57.5, 82.3, 87.6,
113.3, 113.9, 114.1, 123.8, 127.7, 128.6, 130.9, 132.3, 133.3, 138.8,
154.6, 159.9, 199.2.
MS (ESI): m/z = 313 [M + Na]+.
Anal. Calcd for C20H18O2: C, 82.73; H, 6.25. Found: C, 82.54; H,
6.17.
MS (ESI): m/z = 343 [M + Na]+.
Anal. Calcd for C21H20O3: C, 78.73; H, 6.29. Found: C, 78.67; H,
6.14.
Compound 9b
Yield: 68%; colorless gum.
Compound 9f
Yield: 69%; white solid; mp 81–82 °C.
IR (KBr): 1668, 2223, 2923, 3047 cm–1.
IR (neat): 1664, 2229, 2920, 3056 cm–1.
1H NMR (CDCl3, 400 MHz): d = 2.39 (s, 3 H, CH3), 4.96 (s, 2 H,
OCH2), 6.65 (dd, J = 8.0, 2.0 Hz, 1 H, ArH), 6.74 (d, J = 16.4 Hz,
1 H, CHa=CHb), 6.79 (dd, J = 8.0, 7.6 Hz, 1 H, ArH), 7.12 (d,
J = 8.0 Hz, 1 H, ArH), 7.21 (d, J = 7.6 Hz, 1 H, ArH), 7.33–37 (m,
3 H, ArH), 7.44 (dd, J = 7.6, 1.8 Hz, 2 H, ArH), 7.92 (d,
J = 16.4 Hz, 1 H, CHa=CHb).
13C NMR (CDCl3, 100 MHz): d = 27.2, 57.5, 82.7, 87.5, 113.2,
121.9, 124.1, 127.8, 128.2, 128.5, 129.0, 131.4, 132.0, 132.5, 137.7,
155.4, 199.5.
1H NMR (CDCl3, 400 MHz): d = 1.13 [s, 9 H, C(CH3)3], 2.38 (s,
3 H, CH3), 3.79 (s, 3 H, OCH3), 4.98 (s, 2 H, OCH2), 6.72 (d,
J = 16.4 Hz, 1 H, CHa=CHb), 6.82 (d, J = 8.4 Hz, 2 H, ArH), 6.97
(dd, J = 8.8, 2.4 Hz, 1 H, ArH), 7.16 (d, J = 8.4 Hz, 1 H, ArH), 7.32
(d, J = 8.4 Hz, 2 H, ArH), 7.49 (d, J = 2.4 Hz, 1 H, ArH), 7.82 (d,
J = 16.4 Hz, 1 H, CHa=CHb).
13C NMR (CDCl3, 100 MHz): d = 27.1, 31.3, 34.3, 55.2, 57.5, 83.4,
87.5, 113.7, 114.3, 121.8, 123.4, 127.9, 128.2, 131.1, 131.9, 133.0,
138.5, 155.1, 159.5, 198.7.
MS (ESI): m/z = 299 [M + Na]+.
Anal. Calcd for C19H16O2: C, 82.58; H, 5.84. Found: C, 82.68; H,
5.71.
MS (ESI): m/z = 385 [M + Na]+.
Anal. Calcd for C24H26O3: C, 79.53; H, 7.23. Found: C, 79.37; H,
6.94.
Compound 9c
Yield: 62%; white solid; mp 71–72 °C.
Synthesis of Compounds 10a–f; Typical Procedure
IR (KBr): 1667, 2239, 2922, 3057 cm–1.
A mixture of compound 9a (0.50 mmol), I2 (1.50 mmol) and anhy-
drous NaHCO3 (1.50 mmol) was stirred in anhydrous MeCN (5 mL)
at r.t. for 8 h. The reaction mixture was diluted to 50 mL with
CH2Cl2 and the organic phase was washed successively with 10%
aqueous sodium thiosulfate (20 mL), H2O (20 mL), brine (20 mL),
and dried over anhydrous Na2SO4. The solvent was removed under
reduced pressure and the crude product was purified by silica gel
(230–400 mesh) column chromatography (EtOAc–PE, 1:19) to give
compound 10a as a white solid. Compounds 10b–f were synthe-
sized accordingly.
1H NMR (CDCl3, 400 MHz): d = 2.32 (s, 3 H, CH3), 2.39 (s, 3 H,
CH3), 4.98 (s, 2 H, OCH2), 6.74 (d, J = 16.8 Hz, 1 H, CHa=CHb),
7.04 (d, J = 8.2 Hz, 1 H, ArH), 7.19 (d, J = 8.2 Hz, 1 H, ArH), 7.30–
7.33 (m, 3 H, ArH), 7.39 (s, 1 H, ArH), 7.42 (dd, J = 7.6, 2.0 Hz,
2 H, ArH), 7.91 (d, J = 16.8 Hz, 1 H, CHa=CHb).
13C NMR (CDCl3, 100 MHz): d = 20.5, 27.1, 57.4, 83.6, 87.6, 113.2,
122.1, 123.8, 127.8, 128.3, 128.6, 128.8, 131.0, 131.8, 132.3, 138.7,
154.5, 199.2.
MS (ESI): m/z = 313 [M + Na]+.
Anal. Calcd for C20H18O2: C, 82.73; H, 6.25. Found: C, 82.48; H,
6.35.
Compound 10a
Yield: 90%; white solid; mp 105–106 °C.
IR (KBr): 1667, 2922, 3026 cm–1.
Compound 9d
1H NMR (CDCl3, 400 MHz): d = 2.40 (s, 3 H, CH3), 2.42 (s, 3 H,
CH3), 5.15 (s, 2 H, OCH2), 6.69 (d, J = 7.6 Hz, 1 H, ArH), 6.73 (d,
J = 16.4 Hz, 1 H, CHa=CHb), 6.78 (dd, J = 8.0, 7.6 Hz, 1 H, ArH),
7.08 (d, J = 6.8 Hz, 2 H, ArH), 7.27 (d, J = 6.8 Hz, 2 H, ArH), 7.42
(d, J = 8.0 Hz, 1 H, ArH), 7.82 (d, J = 16.8 Hz, 1 H, CHa=CHb).
13C NMR (CDCl3, 100 MHz): d = 21.4, 27.4, 75.1, 91.3, 121.5,
122.4, 124.8, 127.8, 128.1, 128.6, 129.1, 129.4, 136.7, 137.5, 138.1,
141.5, 152.2, 199.0.
Yield: 65%; colorless gum.
IR (neat): 1666, 2236, 2923, 3062 cm–1.
1H NMR (CDCl3, 400 MHz): d = 2.34 (s, 3 H, CH3), 2.39 (s, 3 H,
CH3), 3.79 (s, 3 H, OCH3), 4.94 (s, 2 H, OCH2), 6.71 (d,
J = 16.4 Hz, 1 H, CHa=CHb), 6.95 (dd, J = 8.8, 2.8 Hz, 1 H, ArH),
7.08–7.12 (m, 4 H, ArH), 7.30 (d, J = 8.0 Hz, 2 H, ArH), 7.92 (d,
J = 16.4 Hz, 1 H, CHa=CHb).
13C NMR (CDCl3, 100 MHz): d = 21.5, 27.2, 55.4, 57.4, 83.5, 87.4,
113.3, 113.7, 114.3, 124.0, 128.2, 128.6, 131.0, 132.8, 133.6, 138.9,
154.3, 159.9, 199.8.
MS (ESI): m/z = 439 [M + Na]+.
Anal. Calcd for C20H17IO2: C, 57.71; H, 4.12. Found: C, 57.57; H,
4.11.
MS (ESI): m/z = 343 [M + Na]+.
Anal. Calcd for C21H20O3: C, 78.73; H, 6.29. Found: C, 78.97; H,
6.33.
Compound 10b
Yield: 85%; white solid; mp 133–134 °C.
IR (KBr): 1668, 2923, 3027 cm–1.
Compound 9e
1H NMR (CDCl3, 400 MHz): d = 2.40 (s, 3 H, CH3), 5.16 (s, 2 H,
OCH2), 6.67 (dd, J = 7.6, 1.6 Hz, 1 H, ArH), 6.74 (d, J = 16.4 Hz,
1 H, CHa=CHb), 6.79 (dd, J = 8.0, 7.6 Hz, 1 H, ArH), 7.19–7.21 (m,
2 H, ArH), 7.42–7.48 (m, 4 H, ArH), 7.82 (d, J = 16.4 Hz, 1 H,
CHa=CHb).
Yield: 67%; white solid; mp 90–91 °C.
IR (KBr): 1668, 2227, 2933, 3057 cm–1.
1H NMR (CDCl3, 400 MHz): d = 2.31 (s, 3 H, CH3), 2.38 (s, 3 H,
CH3), 3.79 (s, 3 H, OCH3), 4.96 (s, 2 H, OCH2), 6.74 (d,
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Benzoxepine and Benzo-2H-pyran Derivatives
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13C NMR (CDCl3, 100 MHz): d = 27.3, 75.1, 92.4, 122.7, 123.8,
127.9, 128.3, 128.5, 128.6, 128.9, 129.2, 130.4, 138.1, 140.0, 141.3,
150.7, 198.9.
(d, J = 8.4 Hz, 2 H, ArH), 7.14 (d, J = 8.8 Hz, 2 H, ArH), 7.43 (d,
J = 2.4 Hz, 1 H, ArH), 7.82 (d, J = 16.4 Hz, 1 H, CHa=CHb).
13C NMR (CDCl3, 100 MHz): d = 27.2, 31.1, 34.2, 55.3, 75.2, 91.1,
113.8, 121.5, 124.5, 124.6, 126.3, 128.0, 130.6, 131.8, 138.2, 141.5,
144.2, 150.2, 159.3, 199.2.
MS (ESI): m/z = 425 [M + Na]+.
Anal. Calcd for C19H15IO2: C, 56.74; H, 3.76. Found: C, 56.51; H,
3.72.
MS (ESI): m/z = 511 [M + Na]+.
Anal. Calcd for C24H25IO3: C, 59.03; H, 5.16. Found: C, 58.84; H,
5.07.
Compound 10c
Yield: 93%; white solid; mp 91–92 °C.
IR (KBr): 1668, 2924, 3024 cm–1.
Acknowledgment
1H NMR (CDCl3, 400 MHz): d = 2.13 (s, 3 H, CH3), 2.40 (s, 3 H,
CH3), 5.11 (s, 2 H, OCH2), 6.46 (s, 1 H, ArH), 6.73 (d, J = 16.8 Hz,
1 H, CHa=CHb), 7.20 (dd, J = 8.0, 2.0 Hz, 2 H, ArH), 7.24 (s, 1 H,
ArH), 7.42–7.49 (m, 3 H, ArH), 7.80 (d, J = 16.4 Hz, 1 H,
CHa=CHb).
13C NMR (CDCl3, 100 MHz): d = 20.6, 27.3, 75.1, 91.6, 122.1,
124.6, 128.0, 128.1, 128.3, 128.6, 129.1, 129.3, 130.8, 137.6, 139.8,
141.7, 150.1, 198.8.
We thank the DST (New Delhi) and CSIR (New Delhi) for financial
assistance. B.S. is grateful to the CSIR (New Delhi) and I.A. is
grateful to the UGC (New Delhi) for their research fellowships. We
also thank the DST (New Delhi) for providing the Perkin–Elmer L
120–000A IR spectrometer, the Bruker DPX-400 NMR spectrome-
ter, and the 2400 series II CHN analyzer under its FIST program.
MS (ESI): m/z = 417 [M + H]+.
References
Anal. Calcd for C20H17IO2: C, 57.71; H, 4.12. Found: C, 57.45; H,
3.97.
(1) Present address: Department of Chemical Science, Tezpur
University, Napaam 784028, Assam, India.
(2) Li, C.; Lee, D.; Graf, T. N.; Phifer, S. S.; Nakanishi, Y.;
Riswan, S.; Setyowati, F. M.; Saribi, A. M.; Soejarto, D. D.;
Farnsworth, N. R.; Falkinham, J. O. III; Kroll, D. J.;
Kinghorn, A. D.; Wani, M. C.; Oberlies, N. H. J. Nat. Prod.
2009, 72, 1949.
Compound 10d
Yield: 88%; white solid; mp 152–153 °C.
IR (KBr): 1667, 2923, 3030 cm–1.
1H NMR (CDCl3, 400 MHz): d = 2.41 (s, 6 H, 2 × CH3), 3.65 (s,
3 H, OCH3), 5.08 (s, 2 H, OCH2), 6.30 (d, J = 3.0 Hz, 1 H, ArH),
6.70 (d, J = 16.8 Hz, 1 H, CHa=CHb), 6.91 (d, J = 3.0 Hz, 1 H,
ArH), 7.08 (d, J = 7.6 Hz, 2 H, ArH), 7.25 (d, J = 7.6 Hz, 2 H,
ArH), 7.81 (d, J = 16.4 Hz, 1 H, CHa=CHb).
13C NMR (CDCl3, 100 MHz): d = 21.4, 27.3, 55.7, 75.2, 92.6, 110.4,
116.0, 122.7, 126.0, 128.1, 129.1, 129.4, 136.5, 137.4, 138.2, 141.5,
146.5, 153.7, 198.9.
(3) Fan, X.; Zi, J.; Zhu, C.; Xu, W.; Cheng, W.; Yang, S.; Guo,
Y.; Shi, J. J. Nat. Prod. 2009, 72, 1184.
(4) Flick, A. C.; Caballero, M. J. A.; Padwa, A. Org. Lett. 2008,
10, 1871.
(5) (a) Zhendong, J.; Ying, K. PCT Int. Appl. WO 2004058738,
2004. (b) Iwata, N.; Wang, N.; Yao, X.; Kitanaka, S. J. Nat.
Prod. 2004, 67, 1106. (c) Hu, H.; Harrison, T. J.; Wilson, P.
D. J. Org. Chem. 2004, 69, 3782.
(6) Korec, R.; Sensch, K. H.; Zoukas, T. Arzneim. Forsch. 2000,
50, 122.
MS (ESI): m/z = 469 [M + Na]+.
Anal. Calcd for C21H19IO3 C, 56.52; H, 4.29. Found: C, 56.47; H,
4.19.
(7) Bonadies, F.; Di Fabio, R.; Bonini, C. J. Org. Chem. 1984,
49, 1647.
(8) Morandim, A. A.; Bergamo, D. C. B.; Kato, M. J.;
Cavalheiro, A. J.; Bolzani, V. S.; Furlan, M. Phytochem.
Anal. 2005, 16, 282.
Compound 10e
Yield: 92%; white solid; mp 130–131 °C.
IR (KBr): 1668, 2920, 3032 cm–1.
(9) Stefan, B.; Larsson, L. G.; Rényi, L.; Ross, S. B.; Thorberg,
S.-O.; Thorell-Svantesson, G. J. Med. Chem. 1998, 41, 1934.
(10) Ishizuka, N.; Matsumura, K.; Sakai, K.; Fujimoto, M.;
Mihara, S.; Yamamori, T. J. Med. Chem. 2002, 45, 2041.
(11) (a) TenBrink, R. E.; McCall, J. M.; Johnson, H. G. J. Med.
Chem. 1980, 23, 1058. (b) TenBrink, R. E.; McCall, J. M.;
Pals, D. T.; McCall, R. B.; Orley, J.; Humphrey, S. J.;
Wendling, M. G. J. Med. Chem. 1981, 24, 64. (c) O’Shea,
D. F.; Sharp, J. T. J. Chem. Soc., Perkin Trans. 1 1995, 515.
(d) Tretter, J. R. US Patent 3514449, 1970; Chem. Abstr.
1970, 73, 35404u. (e) Dictionary of Drugs, 1st ed.; Elks, J.;
Ganellin, C. R., Eds.; Chapman and Hall: London, 1990,
984.
(12) (a) Engler, M.; Anke, T.; Sterner, O.; Brandt, U. J. Antibiot.
1997, 50, 325. (b) Wijnberg, J. B. P. A.; van Veldhuizen, A.;
Swart, H. J.; Frankland, J. C.; Field, J. A. Tetrahedron Lett.
1999, 40, 5767.
(13) Lin, Y. L.; Kuo, H. S.; Wang, Y. W.; Huang, S. T.
Tetrahedron 2003, 59, 1277.
1H NMR (CDCl3, 400 MHz): d = 2.14 (s, 3 H, CH3), 2.39 (s, 3 H,
CH3), 3.87 (s, 3 H, OCH3), 5.09 (s, 2 H, OCH2), 6.51 (s, 1 H, ArH),
6.72 (d, J = 16.4 Hz, 1 H, CHa=CHb), 6.99 (d, J = 8.8 Hz, 2 H,
ArH), 7.12 (d, J = 8.4 Hz, 2 H, ArH), 7.23 (s, 1 H, ArH), 7.80 (d,
J = 16.4 Hz, 1 H, CHa=CHb).
13C NMR (CDCl3, 100 MHz): d = 20.7, 27.3, 55.3, 75.1, 91.8, 113.9,
122.0, 124.9, 127.9, 128.0, 129.3, 130.6, 130.8, 132.0, 137.6, 141.3,
150.2, 159.4, 199.0.
MS (ESI): m/z = 469 [M + Na]+.
Anal. Calcd for C21H19IO3: C, 56.52; H, 4.29. Found: C, 56.33; H,
4.17.
Compound 10f
Yield: 87%; white solid; mp 123–124 °C.
IR (KBr): 1666, 2927, 3035 cm–1.
1H NMR (CDCl3, 400 MHz): d = 1.14 [s, 9 H, C(CH3)3], 2.42 (s,
3 H, CH3), 3.89 (s, 3 H, OCH3), 5.11 (s, 2 H, OCH2), 6.74 (d,
J = 2.4 Hz, 1 H, ArH), 6.76 (d, J = 16.4 Hz, 1 H, CHa=CHb), 6.99
(14) (a) Di Fabio, R.; Micheli, F.; Baraldi, D.; Bertani, B.; Conti,
N.; Dal Forno, G.; Feriani, A.; Donati, D.; Marcchioro, C.;
Messeri, T.; Missio, A.; Pasquarello, A.; Pentassuglia, G.;
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PAPER
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Synthesis 2011, No. 20, 3287–3296 © Thieme Stuttgart · New York