Convenient one-pot protocol for an exclusive synthesis of 4-cyano/ethoxycarbonyl-2,2-dimethyl-2H-chromene and/or 3-cyano/ethoxycarbonyl-2- isopropyl-benzo[b]furan from a single oxo-ylide

Article abstract of DOI:10.1080/00397910601055024

[{2-(Fluoroaryloxy)-2-methyl-propanoyl}-(cyano/ethoxycarbonyl) methylene]triphenylphosphoranes underwent microwave-assisted tandem intramolecular Wittig and Claisen rearrangement and internal cyclization reactions to afford fluoro-substituted 2,2-dimethyl-2H-chromenes and/or 2-isopropyl-benzo[b]furans in good yield. Upon controlled microwave irradiation in the presence of Nafion H catalyst in xylene, the oxo-ylides selectively formed 4-cyano/ethoxycarbonyl-2,2-dimethyl-2H-chromenes. Microwave irradiation of the same oxo-ylide in the presence of K2CO3 as catalyst or in a polar solvent-like sulfolane resulted in the exclusive formation of the corresponding fluoro-substituted 3-cyano/ethoxycarbonyl-2-isopropyl-benzo[b]furans. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910601055024

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Convenient One‐Pot Protocol for
an Exclusive Synthesis of 4‐Cyano/
ethoxycarbonyl‐2,2‐dimethyl‐2H‐chromene
and/or 3‐Cyano/
ethoxycarbonyl‐2‐isopropyl‐benzo[b]furan
from a Single Oxo‐ylide
V. V. V. N. S. Rama Rao a , R. Yadla a & P. Shanthan Rao a
a Fluoroorganics Division, Indian Institute of Chemical Technology,
Hyderabad, India
Published online: 06 Mar 2007.
To cite this article: V. V. V. N. S. Rama Rao , R. Yadla & P. Shanthan Rao (2007) Convenient One‐Pot
Protocol for an Exclusive Synthesis of 4‐Cyano/ethoxycarbonyl‐2,2‐dimethyl‐2H‐chromene and/or
3‐Cyano/ethoxycarbonyl‐2‐isopropyl‐benzo[b]furan from a Single Oxo‐ylide, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 37:4, 535-543, DOI:
10.1080/00397910601055024
To link to this article: http://dx.doi.org/10.1080/00397910601055024
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Synthetic Communicationsw, 37: 535–543, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910601055024
Convenient One-Pot Protocol for an
Exclusive Synthesis of 4-Cyano/
ethoxycarbonyl-2,2-dimethyl-2H-chromene
and/or 3-Cyano/ethoxycarbonyl-2-
isopropyl-benzo[b]furan from a
Single Oxo-ylide
V. V. V. N. S. Rama Rao, R. Yadla, and P. Shanthan Rao
Fluoroorganics Division, Indian Institute of Chemical Technology,
Hyderabad, India
Abstract: [f2-(Fluoroaryloxy)-2-methyl-propanoylg-(cyano/ethoxycarbonyl) methyl-
ene]triphenylphosphoranes underwent microwave-assisted tandem intramolecular
Wittig and Claisen rearrangement and internal cyclization reactions to afford fluoro-
substituted 2,2-dimethyl-2H-chromenes and/or 2-isopropyl-benzo[b]furans in good
yield. Upon controlled microwave irradiation in the presence of Nafion H catalyst in
xylene, the oxo-ylides selectively formed 4-cyano/ethoxycarbonyl-2,2-dimethyl-2H-
chromenes. Microwave irradiation of the same oxo-ylide in the presence of K2CO3 as
catalyst or in a polar solvent–like sulfolane resulted in the exclusive formation of the
corresponding fluoro-substituted 3-cyano/ethoxycarbonyl-2-isopropyl-benzo[b]furans.
Keywords: 3-cyano-2-isopropyl-benzo[b]furans, 4-ethoxycarbonyl-2,2-dimethyl-2H-
chromene, intramolecular Wittig and Claisen rearrangement reactions, Nafion H
INTRODUCTION
The 2,2-dimethyl-2H-chromene moiety is present in at least 4000 compounds,
including many natural products and designed molecules for therapeutic
applications.[1,2]
Received June 26, 2006
IICT Communication No. 041018.
Address correspondence to R. Yadla, Fluoroorganics Division, Indian Institute of
Chemical Technology, Hyderabad 500007, India. E-mail: ryadla@yahoo.com
535

536
V. V. V. N. S. R. Rao, R. Yadla, and P. S. Rao
The benzo[b]furan moiety was also a widely distributed substructure in
many natural products and compounds with biological activity.[3] Several
strategies were reported for the synthesis of 2H-chromenes and benzo[b]fur-
ans.[4] Thermolysis of [(aryloxyacetyl) (cyano)methylene] triphenylphosphor-
anes was reported to give 2-alkyl-3-cyano-benzo[b]furan and 4-cyano-2H-
chromene derivatives in moderate yield.[5] Thermal Claisen rearrangement
of ethyl 4-aryloxy-but-2-ynoate[6] resulted in the formation of a mixture of
ethyl 2H-chromene-4-carboxylate and ethyl 2-methyl-benzo[b]furan-3-car-
boxylate. The selectivity mainly depended on the nature of substituents.
Fluorine containing 2,2-dimethyl-2H-chromene-4-carboxylic acid and
2-isopropyl-benzo[b]furan-3-carboxylic acid derivatives have hitherto not
been reported. The carboxylic acid or nitrile function could be effectively
used for attaching various structural units to these compounds. In this com-
munication, we report an efficient and exclusive one-pot synthesis of
fluorine containing 4-cyano/ethoxycarbonyl-2,2-dimethyl-2H-chromenes
9a–c and 3-cyano/ethoxycarbonyl-2-isopropyl-benzo[b]furans 12a–c from
the same substrate using different catalysts under microwave irradiation
conditions by varying certain reaction parameters.
RESULTS AND DISCUSSION
The fluoro-substituted [f2-(phenoxy)-2-methyl-propanoylg-(cyano/ethoxy-
carbonyl)methylene] triphenylphosphoranes 3a–c were obtained in good
yield by reacting the corresponding [(cyano/ethoxycarbonyl)methylene]
triphenylphosphorane 1a/1b with the respective 2-(fluorophenoxy)-2-methyl-
propanoyl chloride 2a–c in the presence of triethylamine. Ethyl bromoisobu-
tyrate and the corresponding fluorophenol were reacted for 3 h in the presence
of K2CO3/acetone to obtain ethyl fluorophenoxy-2-methyl-propanoate. The
ester was hydrolyzed and the resulting acid was reacted with thionyl
chloride to obtain the fluorophenoxy-2-methyl-propanoyl chloride. The
[f2-(4-fluorophenoxy)-2-methyl-propanoylg-(ethoxycarbonyl)methylene] tri-
phenylphosphorane 3a, f2-(4-fluorophenoxy)-2-methyl-propanoylg-, and
f2-(2,4-difluorophenoxy)-2-methyl-propanoylg-(cyano)methylenetriphenylpho-
sphoranes 3b and 3c were individually subjected to controlled microwave
irradiation (300 W) for 15–18 min in xylene in the presence of Nafion H. Puri-
fication of the reaction mixture by column chromatography on silica gel
afforded 2,2-dimethyl-4-ethoxycarbonyl-6-fluoro-2H-chromene 9a, 4-cyano-
2,2-dimethyl-6-fluoro-2H-chromene 9b, and 4-cyano-6,8-difluoro-2,2-
dimethyl-2H-chromene 9c, respectively, in moderate yield, along with
1
unreacted phosphorane 3a–c and triphenylphosphine oxide 5. The H NMR
spectra of the chromenes 9a–c contained signals due to the lone olefinic
proton around d 6.35–6.5 (s, 1H) and the gem-dimethyl group in the region
1.39–1.52 ppm (s, 6H) apart from the respective aromatic protons. The 2,2-
dimethyl-4-ethoxycarbonyl-6-fluoro-2H-chromene 9a showed additional

One-Pot Protocol Synthesis
537
signals due to the –OCH2CH3 of the ester group at d 1.34 (t, 3H) and 4.22 ppm
(q, 2H). The ester carbonyl absorption band of 9a was seen at 1735 cm21 in
the IR spectrum. The nitrile absorption bands in the cases of 9b and 9c
were observed at 2234 and 2231 cm21 respectively.
The phosphoranes 3a–c when subjected to microwave irradiation (450
W) in the presence of K2CO3 in xylene or in sulfolane exclusively gave
3-cyano/ethoxycarbonyl-2-isopropyl-benzo[b]furans 12a–c in good yield
along with triphenylphosphine oxide 5. A small amount of starting material
was the only other compound that could be isolated from the reaction
1
mixture. The H NMR spectra of all the benzo[b]furans 12a–c contained a
distinct septet for 1H around d 3.37–3.4 and a doublet for 6H in the range
1.39–1.5 ppm due to the isopropyl group, apart from the respective
aromatic protons. The –OCH2CH3 proton signals of the ester group present
in 12a appeared at d 1.45 (t, 3H) and 4.37 ppm (q, 2H). The IR absorption
band of the ester carbonyl in 12a was observed at 1719 cm21, whereas the
nitrile absorption bands in the case of compounds 12b and 12c were seen at
2228 and 2233 cm21 respectively. The reaction conditions and yield of
products obtained are presented in Table 1.
The phosphoranes 3a–c, the 2H-chromene derivatives 9a–c, and the
benzo[b]furans 12a–c were synthesized for the first time and were well
characterized. The sequence of probable steps involved in the formation of
2H-chromene or benzo[b]furan derivatives and the possible role of the
catalysts employed in their formation is depicted in Scheme 1.
The oxo-ylides 3a–c underwent intramolecular Wittig reaction under
the influence of microwave irradiation to produce the aryl propargylic ethers
4a–c. Under the same reaction conditions, the latter underwent Claisen
rearrangement and aromatization to give the crucial allenylphenol intermedi-
ate 7. It may be inferred that the presence of Nafion H in a nonpolar solvent at
low microwave energy favored a [1,5-H] shift, resulting in the ortho-quinone
monomethide intermediate 8, which readily underwent electrocyclic ring
closure to generate the 2,2-dimethyl-2H-chromene derivatives 9a–c.
Table 1. Synthesis of 2H-chromenes 9a–c and benzo[b]furans 12a–c
2H-Chromenes
9a–c
Benzo[b]furans 12a–c
K2CO3/xylene Sulfolane
Nafion H/xylene
Time Yield Time Yield Time
(min) (%) (min)
Yield
(%)
Entry Ylide
Z
R
(min)
(%)
1
2
3
3a
3b
3c
CO2C2H5
CN
CN
H
16
17
17
74
67
69
9
11
10
83
85
84
15
18
16
63
35
41
H
F

538
V. V. V. N. S. R. Rao, R. Yadla, and P. S. Rao
Scheme 1. Synthesis of benzo[b]furans 12 and 2H-chromenes 9.
It was reported[7] that polar solvents, high temperatures, and the presence
of a base such as K2CO3 favored dissociation of the allenylphenol intermedi-
ates such as 7 to generate the corresponding phenoxide ions 10. The ortho-
allenylphenolate anion 10 can only cyclize onto the central allenic carbon,
followed by proton abstraction from the medium to generate the

One-Pot Protocol Synthesis
539
2-alkylidene-2,3-dihydrobenzo[b]furan 11, which readily rearranges to the
fully aromatized 2-isopropyl-benzo[b]furan derivatives 12a–c.
Claisen rearrangement of phenyl propargylic ethers was conducted by
heating the substrate for several hours in a high boiling solvent. In thermal
Claisen rearrangement of phenyl propargylic ethers, it was reported that the
presence of gem-dimethyl group on the propargyl moiety[8,9] or an electron-
withdrawing group on the acetylenic carbon[6] favored 2H-chromene
formation, whereas the presence of polar substituents favored[5,7,10] benzo[b]-
furan formation. It was interesting to find the formation of 2-isopropyl-
benzo[b]furans 12a and 12c as major products along with less than 10%
2,2-dimethyl-2H-chromenes when the phosphoranes 3a and 3c were
subjected to microwave irradiation at 450 W power in sulfolane even in the
presence of Nafion H.
Claisen rearrangement of the in situ generated aryl propargylic ethers
4a–c took place under the influence of microwave energy in a much shorter
duration. The nature of substituents, the nature of catalyst employed, the
reaction medium, and the reaction conditions, including the reaction
temperature/microwave energy, determined the selectivity toward either
2H-chromene 9 or benzo[b]furan 12 formation. From the present study, it
may be concluded that Nafion H–catalyzed and controlled microwave
irradiation (300 W) of [f(aryloxy)-2-methyl-propanoylg-(cyano/ethoxycarbo-
nyl) methylene] triphenylphosphoranes 3a–c in non-polar solvents offered a
novel one-pot laboratory protocol for the synthesis of 4-(cyano/ethoxy-
carbonyl)-2,2-dimethyl-2H-chromenes 9a–c. 3-(Cyano/ethoxycarbonyl)-2-
isopropyl-benzo[b]furans 12a–c could be exclusively obtained in good
yield from the phosphoranes 3a–c under higher microwave power (600 W)
at 1358C, either in a polar solvent such as sulfolane or in the presence of a
base in a nonpolar solvent.
EXPERIMENTAL
Apparatus and Methods
Melting points were determined in open glass capillaries on a Fisher Johns
melting-point-apparatus and are uncorrected. IR spectra were recorded on
1
FT-IR Schimadzu Perkin-Elmer 1310 infrared spectrophotometer. H NMR
(200-MHz) and 13C NMR (50-MHz) spectra were recorded on Varian
Gemini spectrometer in CDCl3 solvent using TMS as internal standard.
Mass spectra were recorded on a VG micromass 7070H instrument at
70 eV. Elemental analyses were carried out on a Elemental Vario EL
(Germany) apparatus. Microwave irradiation was carried out using a sealed
tube (Aldrich, Ace pressure tube, 10.2 cm, 15 mL) in a BPL BMO 700T
microwave oven.

540
V. V. V. N. S. R. Rao, R. Yadla, and P. S. Rao
Synthesis of Oxo-ylides 3
General Procedure for the Synthesis of [f(2-Aryloxy)-2-methyl-
propanoylg-alkylidene] triphenylphosphoranes
To a well-stirred suspension of [(cyano/ethoxycarbonyl)methylene] triphe-
nylphosphorane 1a/1b prepared[11] in situ from [(cyano/ethoxycarbonyl)-
methyl] triphenylphosphonium chloride (2 mmol) and triethylamine
(4 mmol) in dry dichloromethane, 2-aryloxy-2-methyl-propanoyl chloride
(2 mmol) in dry dichloromethane (4 mL) was added dropwise, and the
reaction mixture was stirred for 14 h. The reaction mixture was diluted with
dichloromethane (10 mL) and washed with water (2 ꢀ 15 mL). The organic
layer was separated and dried over anhydrous sodium sulphate. The solvent
was removed on a rotavapor, and the crude [f(2-aryloxy)-2-methyl-propa-
noylgalkylidene] triphenylphosphorane 3a–c was purified by recrystallization
from a 1:4 mixture of hexane and ethyl acetate.
Data
[f2-(4-Fluorophenoxy)-2-methyl-propanoylg-(ethoxycarbonyl) methylene]
triphenylphosphorane (3a). Yield: 87%, solid, mp 1538C; dH (200 MHz,
CDCl3): 0.61 (t, 3H, J ¼ 7.1 Hz), 1.62 (s, 6H), 3.37 (q, 2H, J ¼ 7.1 Hz),
6.41–6.50 (m, 2H), 6.56–6.70 (m, 2H), 7.36–7.67 ppm (unresolved, 15H);
IR nmax (cm21): 3048, 2925, 1713, 1593, 1104; MS (EI) m/z: 483 (Mþ-
OC2H5, 2), 375 (100), 303 (12), 277 (7), 262 (3), 91 (65).
[f2-(4-Fluorophenoxy)-2-methyl-propanoylg-cyanomethylene]triphenyl-
phosphorane (3b). Yield: 89%, solid, mp 2108C; dH (200 MHz, CDCl3):
1.62 (s, 6H), 6.72–6.84 (m, 4H), 7.42–7.70 ppm (unresolved, 15H); IR
nmax (cm21): 3053, 2926, 2180, 1572, 1343, 1109; MS (EI) m/z: 481 (Mþ,
16), 328 (100), 279 (5), 262 (3), 199 (4), 183 (10).
[f2-(2,4-Difluorophenoxy)-2-methyl-propanoylg-cyanomethylene]triphenyl-
phosphorane (3c). Yield: 86%, solid, mp 1718C; dH (200 MHz, CDCl3): 1.60
(s, 6H), 6.57 (m, 1H), 6.78–6.92 (m, 2H) and 7.42–7.70 ppm (unresolved,
15H); IR nmax (cm21): 3059, 2921, 2171, 1570, 1446, 1113; MS (LSIMS)
m/z: 500 (MHþ, 28), 328 (76), 278 (100), 277 (81).
Synthesis of 2H-Chromenes 9
General Procedure for the Synthesis of Fluoro-substituted 2,2-Dimethyl-
4-cyano/ethoxycarbonyl-2H-chromenes
The [f2-[(aryloxy)-2-methyl-propanoyl] (cyano/ethooxycarbonyl)methylene]
triphenylphosphorane 3a–c (2g) taken in commercial xylene (2 mL) was

One-Pot Protocol Synthesis
541
placed in a thick-walled glass tube fitted with a Teflonw screw cap along with
Nafion H (in small pieces, 20 mg) and subjected to controlled microwave
irradiation at 300 W power for 13–16 min with external cooling. The
reaction mixture was filtered, and the solid was washed with dichloromethane
(10 mL). The washings combined with the organic layer (filtrate) were con-
centrated and purified by column chromatography on silica gel (100–200
mesh) using hexane as eluent. Concentration of the initial fractions afforded
the corresponding 2,2-dimethyl-2H-chromene 9a–c. The later fractions
eluted with a 1:1 mixture of hexane and ethyl acetate contained the starting
material followed by triphenylphosphine oxide 5.
Data
Ethyl 2,2-dimethyl-6-fluoro-2H-chromene-4-carboxylic acid ester (9a).
Liquid; dH (200 MHz, CDCl3): 1.34 (t, 3H, J ¼ 7.1 Hz), 1.39 (s, 6H),
3
4.22 (q, 2H, J ¼ 7.1 Hz), 6.51 (s, 1H), 6.59 (dd, 1H, JH-H ¼ 9.0 Hz,
3
3
4JH-F ¼ 4.1 Hz, C8-H), 6.76 (ddd, 1H, JH-H ¼ 9.0 Hz, JH-F ¼ 8.7 Hz,
3
4
4JH-H ¼ 3.0 Hz, C7-H), 7.65 ppm (dd, 1H, JH-F ¼ 7.9 Hz, JH-H ¼ 3.0 Hz,
C5-H); dC (50 MHz, CDCl3): 14.2 (s, CH2-CH3), 26.5 (s, CH3 on C2), 61.1
2
(s, -OCH2-), 75.4 (s, -C2), 112.9 (d, JC-F ¼ 26.3 Hz, -C5), 115.9 (d,
2JC-F ¼ 23.5 Hz, -C7), 117.6 (d, JC-F ¼ 8.1 Hz, -C8), 119.4 (d, JC-F
¼
3
3
9 Hz, -C10), 124.8 (s, -C4), 140.7 (s, -C3), 148.8 (s, -C9), 157.2 (d,
1JC-F ¼ 236.9 Hz, -C6), 164.9 (s, -C ¼ O); IR nmax (cm21): 2925, 1735,
1465, 1165; MS (EI) m/z: 250 (Mþ, 18), 235 (100), 207 (7).
2,2-Dimethyl-6-fluoro-2H-chromene-4-carbonitrile (9b). Liquid; dH
¼
3
(200 MHz, CDCl3): 1.40 (s, 6H), 6.35 (s, 1H), 6.71 (dd, 1H, JH-H
9.0 Hz, 4JH-F ¼ 4.5 Hz, C8-H), 6.87 (ddd, 1H, 3JH-H ¼ 9.0 Hz,
4
3
3JH-F ¼ 7.6 Hz, JH-H ¼ 3.0 Hz, C7-H), 7.0 ppm (dd, 1H, JH-F ¼ 7.9 Hz,
4JH-H ¼ 3.0 Hz, C5-H); IR nmax (cm21): 3049, 2925, 2234, 1594,1479,
1172; MS (EI) m/z: 203 (Mþ, 22), 188 (100).
2,2-Dimethyl-6,8-difluoro-2H-chromene-4-carbonitrile (9c). Liquid; dH
3
(200 MHz, CDCl3): 1.52(s, 6H), 6.48(s, 1H), 6.85 (ddd,1H, JH-F ¼ 9.0 Hz,
4
3
3JH-F ¼ 9.0 Hz, JH-H ¼ 2.6 Hz, C7-H), 6.90 ppm (dd, 1H, JH-F ¼ 9.0 Hz,
4JH-H ¼ 2.6 Hz, C5-H); IR nmax (cm21): 3046, 2925, 2231, 1475, 1192; MS
(EI) m/z: 221 (Mþ, 15), 206 (100), 202 (40),149 (50), 105 (95).
Synthesis of Benzo[b]furans 12
General Method for the Synthesis of 2-Methyl-3-cyano/
ethoxycarbonyl-benzo[b]furans
This procedure was illustrated by taking one representative example. [f2-(4-
Fluorophenoxy)-2-methyl-propanoylg-(cyano)methylene]triphenylphosphorane

542
V. V. V. N. S. R. Rao, R. Yadla, and P. S. Rao
3b (2.0 g) dissolved in commercial xylene (2 mL) containing a drop of water
was placed, along with 20 mg of K2CO3, in a pressure tube fitted with a
Teflonw screw cap and subjected to microwave irradiation at 600 W power
for 17 min with intermittent cooling after every 3–4 min to avoid boiling
the solvent away. The reaction mixture was cooled to room temperature and
filtered. The solid was washed with dichloromethane (10 mL); the combined
washings along with organic layers were concentrated on a rotavapor and
purified by column chromatography on silica gel (100–200 mesh) using
hexane as eluent. The initial fractions after solvent removal afforded
3-cyano-5-fluoro-2-isopropyl-benzo[b]furan 12b. The later fractions eluted
with a 1: 1 mixture of hexane and ethyl acetate contained triphenylphosphine
oxide 5. [f2-(2,4-Difluorophenoxy)-2-methyl-propanoylg-(cyano)methylene]
triphenylphosphorane 3c and [f2-(4-fluorophenoxy)-2-methyl-propanoylg-
(ethoxycarbonyl)methylene] triphenylphosphorane 3a were decomposed
similarly to get the corresponding 2-isopropyl-benzo[b]furans 12c and 12a
respectively.
Data
Ethyl 5-fluoro-2-isopropyl-benzo[b]furan-3-carboxylic acid ester (12a).
Liquid; dH (200 MHz, CDCl3): 1.39 (d, 6H, J ¼ 6.9 Hz), 1.45 (t, 3H,
J ¼ 7.1 Hz), 4.0 (heptet, 1H, 6.9 Hz), 4.37 (q, 2H, J ¼ 7.1 Hz), 6.96 (ddd,
3
3
4
1H, JH-H ¼ 9.0 Hz, JH-F ¼ 8.7 Hz, JH-H ¼ 2.6 Hz, C6-H), 7.35 (dd, 1H,
4
3
3JH-H ¼ 9.1 Hz, JH-F ¼ 4.1 Hz, C7-H), 7.57 ppm (dd, 1H, JH-F ¼ 7.9 Hz,
4JH-H ¼ 2.6 Hz, C4-H); dC (50 MHz, CDCl3): 14.4 (s, -CH2CH3), 20.4 [s,
-CH(CH3)2 on C2], 27.7 [s, -CH(CH3)2 on C2], 60.3 (s, -OCH2CH3), 107.9
2
3
(d, JC-F ¼ 26.1 Hz, -C4), 111.5 (d, JC-F ¼ 9.7 Hz, -C7), 111.8
2
3
(d, JC-F ¼ 26.8 Hz, -C6), 127.4 (d, JC-F ¼ 11.3 Hz, -C9), 149.7 (s, C8),
1
159.8 (d, JC-F ¼ 238.7 Hz, -C5), 163.9 (s, -COO-), 173.1 ppm (s, -C2); IR
nmax (cm21): 2925, 1719, 1599, 1460, 1219; MS (EI) m/z: 250 (Mþ, 98),
235 (16), 221 (71), 207 (35), 203 (100).
5-Fluoro-2-isopropyl-benzo[b]furan-3-carbonitrile (12b). Liquid; dH
(200 MHz, CDCl3): 1.42 (d, 6H, J ¼ 6.9 Hz), 3.37 (heptet, 1H, J ¼ 6.9 Hz),
3
3
4
7.04 (ddd, 1H, JH-H ¼ 8.9 Hz, JH-F ¼ 8.7 Hz, JH-H ¼ 2.6 Hz, C6-H), 7.29
3
4
(dd, 1H, JH-F ¼ 8.7 Hz, JH-H ¼ 2.6 Hz, C4-H), 7.39 ppm (dd, 1H,
4
3JH-H ¼ 8.9 Hz, JH-F ¼ 4.1 Hz, C7-H); IR nmax (cm21): 3048, 2926, 2228,
1471, 1182; MS (EI) m/z: 203 (Mþ, 99), 202 (62), 188 (100).
5,7-Difluoro-2-isopropyl-benzo[b]furan-3-carbonitrile (12c). Solid, mp
94–958C; dH (200 MHz, CDCl3): 1.53 (d, 6H, J ¼ 6.9 Hz), 3.94 (heptet,
1H, J ¼ 6.9 Hz), 6.92 (ddd, 1H, 3JH-F ¼ 9.7 Hz, 3JH-F ¼ 9.7 Hz,
3
4
4JH-H ¼ 2.4 Hz),7.15 ppm (dd, 1H, JH-F ¼ 8.3 Hz, JH-H ¼ 2.4 Hz); IR
nmax (cm21): 3056, 2233, 1482; MS (EI) m/z: 221 (Mþ, 20), 206 (100), 200
(73), 184 (14).

One-Pot Protocol Synthesis
ACKNOWLEDGMENTS
543
The authors are thankful to J. S. Yadav, Director, Indian Institute of Chemical
Technology. V. V. V. N. S. R. R is thankful to the Council of Scientific and
Industrial Research, New Delhi, for the financial support.
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