Oxidative addition of 1,3-dicarbonyl compounds to terminal acetylenes mediated by cerium(IV) ammonium nitrate

Article abstract of DOI:10.1055/s-0030-1260095

Cerium(IV) ammonium nitrate mediated oxidative addition of 1,3-dicarbonyl compounds to terminal acetylenes to yield multisubstituted furan derivatives is reported here. The simplicity of the reaction and the ease of execution are particularly noteworthy.

Full text of DOI:10.1055/s-0030-1260095

2466
PAPER
Oxidative Addition of 1,3-Dicarbonyl Compounds to Terminal Acetylenes
Mediated by Cerium(IV) Ammonium Nitrate
C
A
N
-Mediated O
x
k
idative Addi
h
tion il Sivan,a Ani Deepthi,*a Vidya Nandialathb
a
Department of Chemistry, Amrita Vishwa Vidyapeetham, Kollam 690525, India
Fax +91(476)2896178; E-mail: anideepthi@gmail.com
b
AstraZeneca Pvt. Ltd., Bangalore 560024, India
Received 21 March 2011; revised 7 May 2011
As an initial experiment, 1,3-diphenylpropane-1,3-dione
(1a) was treated with phenylacetylene (2a) in 1:1 molar
ratio in acetonitrile as solvent using 2.3 mmol of CAN at
room temperature in an atmosphere of nitrogen. On com-
pletion of the reaction as indicated by TLC, the reaction
mixture was worked up and subjected to column chroma-
tography on silica gel (100–200 mesh) to yield a product
which was characterized by spectral analysis to be the tet-
rasubstituted furan derivative 3a in 56% yield (Table 1
entry 3). Optimization of the reaction conditions (Table 1)
led to the formation of the same product in 90% overall
yield (entry 5).
Abstract: Cerium(IV) ammonium nitrate mediated oxidative addi-
tion of 1,3-dicarbonyl compounds to terminal acetylenes to yield
multisubstituted furan derivatives is reported here. The simplicity of
the reaction and the ease of execution are particularly noteworthy.
Key words: cerium(IV) ammonium nitrate, oxidative addition, ter-
minal acetylenes, multisubstituted furans, 1,3-dicarbonyl com-
pounds
Multisubstituted furans are important intermediates in or-
ganic synthesis.1 In addition furans are also structural ele-
ments in many natural products and pharmaceutically
important compounds.2 There are numerous methods for
the synthesis of furans owing to their tremendous impor-
tance,3 but there are few syntheses based on the single-
electron oxidative addition mechanism.4 In our pursuit of
developing mild synthetic protocols for heterocyclic and
carbocyclic constructions using oxidants like cerium(IV)
ammonium nitrate (CAN), we came across a mild method
for furan synthesis which is reported in this paper. It is
well known that CAN is a very versatile reagent for the
single-electron oxidation of a variety of organic com-
pounds.5 Over the years, CAN has been used in a variety
of C–C and C–heteroatom bond formations both stoichio-
metrically and catalytically.6 The facile formation of dihy-
drofurans by the oxidative addition of 1,3-dicarbonyl
compounds to alkenes is one of the most exploited reac-
tions mediated by this reagent.7 The trapping of the elec-
trophilic radical generated by CAN from 1,3-diones has
been successfully performed using various electron-rich
substrates like vinyl sulfides,8 glycals,9 and
methylenecyclopropanes10 to cite a few. To the best of our
knowledge, apart from some isolated reports,11,12 there has
not been a systematic investigation of the CAN-mediated
addition of malonate radicals to terminal acetylenes. On
the basis of mechanistic considerations, we surmised that
the use of acetylenes instead of alkenes would probably
result in the formation of furans in place of dihydrofurans.
As expected, detailed experiments performed in our labo-
ratory in this direction have shown the facile formation of
multisubstituted furan derivatives in moderate to good
yields.
The IR spectrum of 3a revealed OH stretching at 3459
cm–1 while the benzoyl carbonyl stretching was observed
at 1663 cm–1. The OH proton was observed at d = 7.28
ppm in the 1H NMR. The benzoyl carbon was observed at
d = 193.57 ppm while the furan carbons resonated at d =
192.59, 188.41, 171.54, and 153.00 ppm in the 13C NMR
spectrum. The mass spectral data also matched with the
assigned structure.
Table 1 CAN-Mediated Reaction of 1,3-Diphenylpropane-1,3-di-
one (1a) with Phenylacetylene (2a)
O
H
O
Ph
O
O
CAN, solvent
+
Ph
Ph
Ph
Ph
O
1a
2a
3a
Entry CAN
(mmol)
Solvent
Temp
(°C)
Time
(h)
Atm
Yield
(%)
1
2
3
4
5
1.1
MeOH
MeOH
MeCN
MeCN
MeCN
r.t.
12
12
12
12
3
N2
N2
N2
N2
air
30
37
56
40
90
2.3
2.3
2.3
2.3
0–r.t.
0–r.t.
0–r.t.
–5–r.t.
The doubling of the product yield on increasing the
amount of CAN revealed that two moles of CAN were re-
quired for the reaction (entries 1 and 3). An appreciable
increase in the product yield was also observed by passing
air through the reaction mixture (entries 4 and 5). The rate
of the reaction was also found to increase by passing air
which proves the catalytic effect of air in promoting this
SYNTHESIS 2011, No. 15, pp 2466–2470
x
x.
x
x
.
2
0
1
1
Advanced online publication: 07.07.2011
DOI: 10.1055/s-0030-1260095; Art ID: Z31311SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
CAN-Mediated Oxidative Addition
2467
reaction. The increase in the reaction rate can be probably ping by the nitrato radical yields VI. The mass spectral
attributed to the re-oxidation of the Ce(III) species back to analysis (FAB+) of the crude mixture of the reaction of 1a
Ce(IV), thus maintaining the concentration of Ce(IV) in shows a peak at m/z 386.57 (m/z calcd for VI C23H15NO5
the reaction mixture.
is 386.37). On the basis of a similar literature precedent12
it can be presumed that hydrolysis of the nitrate VI during
workup and/or the separation procedure yields the final
hydroxylated product 3a. The exact driving force for con-
version of the trisubstituted furan into the tetrasubstituted
furan is unknown, but the extra stability achieved due to
the strong intramolecular H-bonding of the hydroxy group
proton to the carbonyl oxygen giving rise to a six-mem-
bered H-bonded structure may be invoked to explain the
formation of the product 3a. Alternate pathways for the
formation of the product 3a are as follows. Nitrato radi-
cals are proved oxygen atom synthons for the radical cy-
clization reactions of alkynes.13 Homolytic fragmentation
of the labile O–NO2 bond of VI can yield VII which can
abstract a hydrogen atom and form the product 3a. Alter-
natively, trapping of the intermediate V by molecular
oxygen and its rearrangement to the final product may
also occur. The exact mechanism for the formation of 3a
may probably involve all these pathways.
Subsequently, the generality of the reaction was studied
using several 1,3-dicarbonyl compounds and the results
are summarized in Table 2.
Table 2 CAN-Mediated Reaction of 1,3-Dicarbonyl Compounds
1b–h with Phenylacetylene (2a)
O
H
R1
O
O
O
CAN (2.3 mmol)
MeCN, air, 3 h
+
R1
R2
R2
Ph
O
1b–h
2a
3b–h
Entry
1,3-Dione R1
R2
Product Yield (%)
1
2
3
4
5
6
7
1b
1c
1d
1e
1f
Ph
Me
3b
3c
3d
3e
3f
65
31
42
56
81
77
30
Me
Me
OEt
Oi-Pr
Ph
OEt
Oi-Pr
OEt
OEt
OMe
We then extended our studies to cyclic 1,3-dicarbonyl
compounds. It was observed that the reaction of dimedone
(5) with phenylacetylene (2a) in the presence of CAN led
to the formation of the trisubstituted furan 6a in 56% yield
(Table 3, entry 1). The structure of the product was unam-
biguously confirmed based on spectral analysis.
1g
1h
Me
3g
3h
3-pyridyl
The stability of the fused furan 6a is probably the reason
why it is not further oxidized to form the tetrasubstituted
furan as in the case of the reaction of acyclic diones even
by passing air. However the reaction of other cyclic di-
ones like cyclohexane-1,3-dione, cyclopentane-1,3-dione,
indane-1,3-dione, and Meldrum’s acid did not lead to any
product formation. The reaction of these latter diones in
methanol as the solvent led to intractable reaction mix-
tures, while in acetonitrile solvent, the reaction resulted in
Mechanistically, the reaction is presumed to occur via the
initial formation of the electrophilic radical I from the di-
carbonyl compound 1a followed by its addition to the less
hindered side of the terminal acetylene 2a to generate the
vinyl radical species II (Scheme 1). The latter is a highly
reactive species, known in the literature13 which probably
undergoes cyclization followed by CAN oxidation to
yield III which gets converted into the trisubstituted furan
IV. Further oxidation by CAN to the radical V and trap-
O
O
O
O
H
Ph
CAN
Ph
Ph
•
CAN
Ph
Ph
Ph
•
Ph
+
O
O
Ph
III
O
Ph
Ph
1a
Ph
O
I
II
O
O
O
ONO2
Ph
Ph
Ph
•
workup
ONO2
•
CAN
air
3a
Ph
Ph
O
Ph
.
Ph
Ph
Ph
O
VI
O
O
V
IV
•
– NO2
H
O
•
O
O
Ph
Ph
H atom abstraction
Ph
Ph
Ph
Ph
O
O
3a
VII
Scheme 1 Postulated mechanism for the reaction
Synthesis 2011, No. 15, 2466–2470 © Thieme Stuttgart · New York

2468
A. Sivan et al.
PAPER
round-bottom flask fitted with a pressure-equalizing funnel contain-
ing a soln of CAN (2.3 mmol) in anhyd MeCN (5 mL). Air was then
bubbled through both the solns. The CAN soln was then added
dropwise to the flask and the mixture was allowed to stir at –5 °C
and the temperature was gradually allowed to rise to r.t. When the
starting materials were fully consumed as indicated by TLC, the sol-
vent was rotary evaporated and the crude residue was extracted with
CH2Cl2. The organic layer was washed with brine soln (3 × 10 mL)
and dried (anhyd Na2SO4). After removing the solvent, the residue
was subjected to column chromatography (silica gel, 100–200
mesh, hexane–EtOAc) to yield the product.
the oxidation of phenylacetylene alone yielding a benzoic
acid derivative.
Subsequently, various other terminal acetylenes 2b–g
were reacted with dimedone (5) in the presence of CAN;
the fused furans 6b–g were formed in moderate yields
(Table 3). Terminal acetylenes with electron-withdrawing
groups attached to the phenyl ring were found to be slug-
gish in their reactivity.
Table 3 CAN-Mediated Reaction of Dimedone (5) with Arylacety-
lenes 2a–g
(4-Hydroxy-2,5-diphenylfuran-3-yl)phenylmethanone (3a)
O
Yellow oil; yield: 306 mg (90%).
O
IR (neat): 3459, 3065, 1663, 1597, 1448, 1014 cm–1.
CAN (2.3 mmol)
MeCN, 3 h
Ar
+
1H NMR (500 MHz, CDCl3): d = 8.05–8.03 (m, 1 H), 7.99–7.97 (m,
1 H), 7.91–7.89 (m, 1 H), 7.84–7.79 (m, 2 H), 7.56–7.48 (m, 2 H),
7.46–7.41 (m, 4 H), 7.39–7.35 (m, 4 H), 7.28 (s, 1 H).
Ar
O
O
5
2
6a–f
13C NMR (125 MHz, CDCl3): d = 193.57, 192.59, 188.41, 171.54,
153.00, 136.34, 135.89, 134.02, 133.97, 133.65, 133.62, 133.58,
130.66, 130.30, 130.22, 129.41, 129.16, 129.01, 128.85, 128.79,
128.68, 128.64, 128.42.
HRMS (EI): m/z [M]+ calcd for C23H16O3: 340.1099; found:
340.1090.
Entry
Acetylene Ar
Product
6a
Yield (%)
1
2
3
4
5
6
7
2a
2b
2c
2d
2e
2f
Ph
56
41
42
44
37
40
21
1-naphthyl
2-naphthyl
4-PhC6H4
4-MeOC6H4
4-MeC6H4
4-ClC6H4
6b
6c
6d
(4-Hydroxy-2-methyl-5-phenylfuran-3-yl)phenylmethanone
(3b)
Yellow oil; yield: 181 mg (65%).
IR (neat): 3369, 3061, 2928, 1692, 1599, 1450 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.92–7.89 (m, 3 H), 7.87–7.86 (m,
1 H), 7.59–7.55 (m, 2 H), 7.46–7.43 (m, 5 H), 2.36 (s, 3 H).
6e
6f
2g
6g
13C NMR (125 MHz, CDCl3): d = 195.56, 194.69, 188.63, 171.41,
150.70, 136.39, 135.87, 134.12, 133.80, 133.61, 130.62, 130.20,
In conclusion we have developed a new method for the
preparation of tetrasubstituted and fused furans by the ox- 130.03, 128.88, 128.84, 128.69, 128.54, 28.18.
HRMS (EI): m/z [M]+ calcd for C18H14O3: 278.0976; found:
278.0981.
idative addition of terminal acetylenes to 1,3-dicarbonyl
compounds in the presence of cerium(IV) ammonium ni-
trate. The prepared furans have potential antioxidant ac-
tivity and this is being tested.
1-(4-Hydroxy-2-methyl-5-phenylfuran-3-yl)ethanone (3c)
Yellow oil; yield: 67 mg (31%).
IR (neat): 3413, 3065, 2922, 1662, 1595, 1448 cm–1.
1H NMR (500 MHz, CDCl3): d = 8.22–7.96 (m, 2 H), 7.68–7.63
(m, 1 H), 7.57–7.46 (m, 3 H), 2.45 (s, 6 H).
13C NMR (125 MHz, CDCl3): d = 202.38, 195.50, 189.56, 152.07,
136.23, 134.26, 130.15, 129.57, 128.88, 128.70, 128.54, 30.66,
27.33.
HRMS (EI): m/z [M]+ calcd for C13H12O3: 216.0820; found:
216.0819.
NMR spectra were recorded at 500 MHz (1H) and 125 MHz (13C)
on a Bruker Avance DPX NMR spectrometer, except for the com-
pounds 6a–g which were recorded at 300 and 75 MHz, relative to
TMS as the internal standard. IR spectra were recorded on a
Shimadzu FT-IR spectrophotometer. Mass spectra were recorded
under FAB or EIMS at 5000 resolution using a Jeol mass spectrom-
eter. Melting points were recorded on a Büchi melting point appa-
ratus and are uncorrected. Cerium(IV) ammonium nitrate (CAN)
was purchased from Merck Specialities Pvt. Ltd. and was used as
such without further purification. Commercial grade anhyd solvents
were used. All reactions were monitored by TLC, visualization was
effected with UV and/or by developing in I2. Gravity column chro-
matography was performed using 100–200 mesh silica gel eluting
with hexane–EtOAc. The phenylacetylene used for the study was
purchased from Aldrich Chemical Co. All other terminal acetylenes
were prepared by Sonogashira coupling method. All 1,3-dicarbonyl
compounds were commercially available and were used as such
without further purification. Dimedone purchased was purified by
recrystallization (acetone).
Ethyl 2-Ethoxy-4-hydroxy-5-phenylfuran-3-carboxylate (3d)
Yellow oil; yield: 116 mg (42%).
IR (neat): 3453, 2967, 1734, 1675, 1597, 1449 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.96–7.84 (m, 1 H), 7.65–7.63
(m, 1 H), 7.53 (s, 1 H), 7.52–7.49 (m, 1 H), 7.34–7.27 (m, 2 H),
4.52–4.19 (m, 4 H), 1.69–1.35 (m, 6 H).
13C NMR (125 MHz, CDCl3): d = 195.23, 187.75, 166.01, 163.22,
161.67, 135.46, 134.76, 133.00, 127.88, 127.75, 127.56, 60.70,
55.78, 13.00, 12.78.
HRMS (EI): m/z [M]+ calcd for C15H16O5: 277.1031; found:
277.1025.
Furans 3a–h and Benzofurans 6a–g; General Procedure
A soln of 1,3-dicarbonyl compound (1.0 mmol) and terminal acety-
lene (1.0 mmol) in anhyd MeCN (5 mL) was added to a two-necked
Synthesis 2011, No. 15, 2466–2470 © Thieme Stuttgart · New York

PAPER
CAN-Mediated Oxidative Addition
2469
Isopropyl 4-Hydroxy-2-isopropoxy-5-phenylfuran-3-carboxy-
late (3e)
HRMS (EI): m/z [M]+ calcd for C16H16O2: 240.1184; found:
240.1180.
Yellow oil; yield: 170 mg (56%).
6,6-Dimethyl-2-naphthalen-1-yl-6,7-dihydrobenzofuran-4(5H)-
one (6b)
White solid; mp 171–173 °C; yield: 120 mg (41%).
IR (KBr): 3056, 2961, 2876, 1685, 1444 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.32 (d, J = 6.8 Hz, 1 H), 7.89–
7.83 (m, 2 H), 7.72 (d, J = 7 Hz, 1 H), 7.57–7.47 (m, 3 H), 6.98 (s,
1 H), 2.88 (s, 2 H), 2.44 (s, 2 H), 1.22 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 193.07, 165.61, 154.02, 134.08,
130.41, 129.25, 128.67, 128.25, 127.85, 127.6, 127.61, 126.86,
126.65, 126.45, 126.11, 125.22, 125.17, 122.71, 121.77, 105.42,
52.21, 37.76, 37.72, 35.30, 28.81.
IR (neat): 3459, 2982, 1733, 1675, 1598, 1449 cm–1.
1H NMR (500 MHz, CDCl3): d = 8.09–8.07 (m, 1 H), 7.98–7.96 (m,
1 H), 7.78 (s, 1 H), 7.61–7.57 (m, 2 H), 7.52–7.28 (m, 1 H), 5.29–
5.11 (m, 2 H), 1.35–1.18 (m, 12 H).
13C NMR (125 MHz, CDCl3): d = 196.26, 188.80, 166.61, 163.82,
162.30, 137.23, 136.23, 134.44, 133.95, 128.94, 128.61, 70.12,
69.27, 21.65, 21.63, 21.48, 21.40.
HRMS (EI): m/z [M]+ calcd for C17H20O5: 304.1311; found:
304.1315.
(2-Ethoxy-4-hydroxy-5-phenylfuran-3-yl)phenylmethanone
(3f)
HRMS (EI): m/z [M]+ calcd for C20H18O2: 290.1340; found:
Yellow oil; yield: 250 mg (81%).
290.1342.
IR (neat): 3319, 2960, 1723, 1682, 1598, 1450 cm–1.
6,6-Dimethyl-2-naphthalen-2-yl-6,7-dihydrobenzofuran-4(5H)-
one (6c)
White solid; mp 137–139 °C; yield: 122 mg (42%).
IR (KBr): 2962, 1681, 1452, 1357, 1216 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.15 (s, 1 H), 7.88–7.84 (m, 3 H),
7.72 (d, J = 8.5 Hz, 1 H), 7.51–7.49 (m, 2 H), 7.01 (s, 1 H), 2.87 (s,
2 H), 2.43 (s, 2 H), 1.20 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 193.62, 171.49, 165.91, 154.67,
133.39, 132.95, 128.62, 128.21, 127.81, 127.14, 126.65, 126.28,
122.55, 122.05, 121.88, 101.41, 52.03, 37.57, 35.32, 28.72.
1H NMR (500 MHz, CDCl3): d = 8.05–8.03 (m, 2 H), 7.88–7.87 (m,
1 H), 7.82–7.79 (m, 1 H), 7.54–7.49 (m, 2 H), 7.48 (s, 1 H), 7.40–
7.36 (m, 4 H), 4.19 (q, J = 18 Hz, 2 H), 1.14 (t, J = 15 Hz, 3 H).
13C NMR (125 MHz, CDCl3): d = 193.26, 188.29, 172.13, 163.72,
145.00, 136.37, 134.25, 133.81, 133.55, 130.35, 129.72, 129.56,
129.03, 128.95, 128.78, 128.68, 128.58, 62.48, 14.06.
HRMS (EI): m/z [M]+ calcd for C19H16O4: 308.1049; found:
308.1045.
1-(2-Ethoxy-4-hydroxy-5-phenylfuran-3-yl)ethanone (3g)
Yellow oil; yield: 189 mg (77%).
HRMS (EI): m/z [M]+ calcd for C20H18O2: 290.1340; found:
290.1341.
IR (neat): 3432, 2957, 1731, 1668, 1597, 1450 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.90–7.85 (m, 1 H), 7.54–7.52
(m, 1 H), 7.44–7.39 (m, 4 H), 4.21–4.11 (m, 2 H), 2.36 (s, 3 H), 1.28
(t, J = 15 Hz, 3 H).
2-Biphenyl-4-yl-6,6-dimethyl-6,7-dihydrobenzofuran-4(5H)-
one (6d)
White solid; mp 170–172 °C; yield: 139 mg (44%).
13C NMR (125 MHz, CDCl3): d = 199.10, 192.63, 188.05, 164.33,
144.78, 140.04, 134.99, 133.09, 131.31, 129.44, 127.75, 62.59,
29.00, 13.00.
HRMS (EI): m/z [M]+ calcd for C14H14O4: 247.0926; found:
247.0936.
IR (KBr): 2955, 1674, 1573, 1445, 1404, 1216 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.71 (d, J = 8.4 Hz, 2 H), 7.63–
7.59 (m, 4 H), 7.44 (uneven t, J = 7.7, 7.1 Hz, 2 H), 7.35 (d, J = 7.2
Hz, 1 H), 6.91 (s, 1 H), 2.84 (s, 2 H), 2.41 (s, 2 H), 1.20 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 193.43, 165.64, 140.79, 140.41,
128.86, 127.54, 127.46, 126.95, 124.35, 121.88, 100.97, 52.05,
37.59, 35.32, 28.76.
(4-Hydroxy-2-methoxy-5-phenylfuran-3-yl)pyridin-3-ylmeth-
anone (3h)
Yellow oil; yield: 89 mg (30%).
HRMS (EI): m/z [M]+ calcd for C22H20O2: 316.1497; found:
316.1498.
IR (neat): 3060, 2956, 1719, 1450, 1266, 1176 cm–1.
1H NMR (500 MHz, CDCl3): d = 8.53 (d, J = 10 Hz, 1 H), 8.12 (d,
J = 5 Hz, 1 H), 7.71 (d, J = 10 Hz, 2 H), 7.46–7.40 (m, 5 H), 7.09
(s, 1 H), 3.38 (s, 3 H).
2-(4-Methoxyphenyl)-6,6-dimethyl-6,7-dihydrobenzofuran-
4(5H)-one (6e)
White solid; mp 131–133 °C; yield: 100 mg (37%).
13C NMR (125 MHz, CDCl3): d = 170.01, 163.36, 153.59, 148.85,
136.00, 132.91, 130.58, 129.25, 129.00, 128.88, 128.53, 128.48,
128.26, 124.14, 117.25, 107.84, 51.86.
HRMS (EI): m/z [M]+ calcd for C17H13NO4: 296.0878; found:
296.0884.
IR (KBr): 3117, 2962, 1681, 1593, 1499, 1452 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.56 (d, J = 8.8 Hz, 2 H), 6.91 (d,
J = 8.8 Hz, 2 H), 6.73 (s, 1 H), 3.83 (s, 3 H), 2.81 (s, 2 H), 2.39 (s,
2 H), 1.18 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 193.51, 165.04, 159.58, 125.44,
122.87, 121.77, 114.24, 99.18, 55.23, 52.04, 37.56, 35.32, 28.77.
6,6-Dimethyl-2-phenyl-6,7-dihydrobenzofuran-4(5H)-one (6a)
White solid; mp 100–102 °C; yield: 134 mg (56%).
HRMS (EI): m/z [M]+ calcd for C17H18O3: 270.1289; found:
270.1291.
IR (KBr): 2962, 2867, 1667, 1431, 1222, 764 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.64 (d, J = 7.3 Hz, 2 H), 7.39 (un-
even t, J = 7.8, 7.2 Hz, 2 H), 7.29 (d, J = 7.3 Hz, 1 H), 6.88 (s, 1 H),
2.83 (s, 2 H), 2.40 (s, 2 H), 1.19 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 193.44, 165.54, 154.59, 129.86,
128.77, 128.03, 123.93, 121.76, 100.84, 52.02, 37.53, 35.29, 28.72.
6,6-Dimethyl-2-p-tolyl-6,7-dihydrobenzofuran-4(5H)-one (6f)
White solid; mp 122–124 °C; yield: 102 mg (40%).
IR (KBr): 3110, 2962, 1681, 1499, 1445, 1222, 838 cm–1.
Synthesis 2011, No. 15, 2466–2470 © Thieme Stuttgart · New York

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A. Sivan et al.
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1H NMR (300 MHz, CDCl3): d = 7.53 (d, J = 8.1 Hz, 2 H), 7.18 (d,
J = 8.0 Hz, 2 H), 6.81 (s, 1 H), 2.81 (s, 2 H), 2.39 (s, 2 H), 2.39 (s,
3 H), 1.18 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 193.48, 165.25, 154.84, 137.88,
129.47, 127.21, 123.93, 121.75, 100.09, 52.03, 37.55, 35.30, 28.75,
21.36.
(2) For selected reviews, see: (a) Hou, X. L.; Yang, Z.; Wong,
H. N. C. Prog. Heterocycl. Chem. 2008, 19, 176. (b) Keay,
B. A.; Dibble, P. W. In Comprehensive Heterocyclic
Chemistry II, Vol. 2; Katritzky, A. R.; Rees, C. W.; Scriven,
E. F. V., Eds.; Elsevier: Oxford, 1997, 395.
(3) (a) Brown, R. C. D. Angew. Chem. Int. Ed. 2005, 44, 850;
and references cited therein. (b) Kirsch, S. F. Org. Biomol.
Chem. 2006, 4, 2076; and references cited therein. (c) Kao,
T. T.; Syu, S.; Jhang, Y. W.; Lin, W. Org. Lett. 2010, 12,
3066.
HRMS (EI): m/z [M]+ calcd for C17H18O2: 254.1340; found:
254.1344.
2-(4-Chlorophenyl)-6,6-dimethyl-6,7-dihydrobenzofuran-
4(5H)-one (6g)
White solid; mp 161–163 °C; yield: 57 mg (21%).
IR (KBr): 3097, 2969, 2928, 1667, 1492, 1452 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.62 (d, J = 8.6 Hz, 2 H), 7.40 (d,
J = 8.6 Hz, 2 H), 6.91 (s, 1 H), 2.86 (s, 2 H), 2.44 (s, 2 H), 1.23 (s,
6 H).
13C NMR (75 MHz, CDCl3): d = 193.25, 165.70, 153.47, 133.79,
129.00, 128.32, 125.10, 121.80, 101.32, 51.95, 37.46, 35.25, 28.68.
(4) Baciocchi, E.; Ruzziconi, R. Synth. Commun. 1988, 18,
1841.
(5) (a) Nair, V.; Deepthi, A. Tetrahedron 2009, 65, 10745.
(b) Nair, V.; Deepthi, A. Chem. Rev. 2007, 107, 1862.
(6) (a) Sridharan, V.; Menendez, J. C. Chem. Rev. 2010, 110,
3805. (b) Nair, V.; Balagopal, L.; Rajan, R.; Mathew, J. Acc.
Chem. Res. 2004, 37, 21. (c) Nair, V.; Panicker, S. B.; Nair,
L. G.; George, T. G.; Augustine, A. Synlett 2003, 156.
(7) Nair, V.; Mathew, J. J. Chem. Soc., Perkin Trans. 1 1995,
187.
(8) Lee, Y. R.; Kang, K. Y.; Lee, G. J.; Lee, W. K. Synthesis
2003, 1977.
HRMS (EI): m/z [M]+ calcd for C16H15ClO2: 274.0794; found:
274.0797.
(9) (a) Yin, J.; Sommermann, T.; Linker, T. Chem. Eur. J. 2007,
13, 10152. (b) Elamparuthi, E.; Kim, B. G.; Yin, J.; Maurer,
M.; Linker, T. Tetrahedron 2008, 64, 11925. (c) Linker, T.;
Schanzenbach, D.; Elamparuthi, E.; Sommermann, T.;
Fudickar, W.; Gyóllai, V.; Somsák, L.; Dimuth, W.;
Schmittel, M. J. Am. Chem. Soc. 2008, 130, 16003.
(10) Nair, V.; Suja, T. D.; Mohanan, K. Synthesis 2006, 2335.
(11) (a) Kobayashi, K.; Mori, M.; Umed, T.; Morikawa, O.;
Konishi, H. Chem. Lett. 1996, 451. (b) Nair, V.; Treesa, P.
M.; Maliakal, D.; Rath, N. P. Tetrahedron 2001, 57, 7705.
(12) Kobayashi, K.; Tanaka, H.; Tanaka, K.; Yoneda, K.;
Morikawa, O.; Konishi, H. Synth. Commun. 2000, 30, 4277.
(13) (a) Wille, U. J. Am. Chem. Soc. 2002, 124, 14.
(b) Jargstorff, C.; Wille, U. Eur. J. Org. Chem. 2003, 3173.
(c) Dreessen, T.; Jargstorff, C.; Lietzau, L.; Plath, C.;
Stademann, A.; Wille, U. Molecules 2004, 9, 480.
Acknowledgment
The authors thank the Department of Science and Technology
(DST), New Delhi for financial assistance. The authors are also ex-
tremely grateful to all members of the organic section of NIIST, Tri-
vandrum for their support. The authors also thank SAIF (DST),
IITM Chennai for EIMS data.
References
(1) For selected reviews, see: (a) Lipshutz, B. H. Chem. Rev.
1986, 86, 795. (b) Lee, H. K.; Chan, K. F.; Hui, C. W.; Yim,
H. K.; Wu, X. W.; Wong, H. N. C. Pure Appl. Chem. 2005,
77, 139.
Synthesis 2011, No. 15, 2466–2470 © Thieme Stuttgart · New York