CAN-promoted, diastereoselective synthesis of fused 2,3-dihydrofurans and their transformation into tetrahydroindoles

Article abstract of DOI:10.1016/j.tet.2010.10.017

The reaction between 1,3-cyclohexanediones and chalcones (or their vinilogs) in the presence of 2.5 equiv of cerium(IV) ammonium nitrate afforded trans-2-arylcarbonyl-3-aryl (or styryl)-2,3,6,7-tetrahydrobenzofuran-4(5H)-ones in good to excellent yields a

Full text of DOI:10.1016/j.tet.2010.10.017

Tetrahedron 66 (2010) 9512e9518
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CAN-promoted, diastereoselective synthesis of fused 2,3-dihydrofurans and their
transformation into tetrahydroindoles
y
*
ꢀ
Swarupananda Maiti, Paramasivan T. Perumal , J. Carlos Menendez
ꢀ
ꢀ
ꢀ
Departamento de Quımica Organica y Farmaceutica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
The reaction between 1,3-cyclohexanediones and chalcones (or their vinilogs) in the presence of
2.5 equiv of cerium(IV) ammonium nitrate afforded trans-2-arylcarbonyl-3-aryl (or styryl)-2,3,6,7-tet-
rahydrobenzofuran-4(5H)-ones in good to excellent yields and in high diastereoselectivities. The method
was also extended to the preparation of derivatives of the 5,6-dihydro-2H-cyclopenta[b]furan-4(3H)-one
system. The fused 2,3-dihydrofuran derivatives were transformed into 1-alkyl-2-acyl-3-aryl-6,7-dihy-
droindole-4(5H)-ones by 2,3-dehydrogenation followed by reaction with primary amines. The direct
reaction of the tetrahydrobenzofuran-4(5H)-one compounds derived from dimedone with amines gave
1-alkyl-2-alkylimino-3-aryl-6,7-dihydroindole-4(5H)-ones, while starting materials derived from 1,3-
cyclohexanedione underwent an unprecedented 2-deacylation reaction and gave 1-alkyl-3-aryl-6,7-di-
hydroindole-4(5H)-ones.
Received 10 September 2010
Received in revised form 6 October 2010
Accepted 8 October 2010
Available online 14 October 2010
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
with the exception of a few examples related to the construction of
2-spiro compounds,7 the stereochemical outcome of the radical-
Oxahydrindanes (hydrobenzo[b]furans) are central structural
cores of a broad range of natural products, such as 3,6-dimethyl-
2,3,3a,4,5,7a-hexahydrobenzofuran, one of the major aroma com-
pounds in the dill herb, paniculide A, evodone, pongamol, iso-
eupatin, the aurones and the tubipofurans, among others, and are
also structural fragments of complex bioactive macrocyclic natural
products like the milbemycins and the avermerctins. While there is
a plethora of methods for the synthesis of fully aromatic benzo[b]
furan derivatives,1 not many general routes are known for the
preparation of the various types of oxhydrindanes.2 Regarding the
particular case of 2,3,4,5,6,7-hexahydrobenzofurans, an efficient
entry has been recently established, based on a pyridine-catalyzed,
three-component reaction between cyclic 1,3-diketones, aromatic
aldehydes and benzyl or phenacyl bromides.3 Following the dis-
covery of the oxidative addition of 1,3-dicarbonyl compounds to
alkenes promoted by one-electron oxidants,4 the oxidative cyclo-
addition of 1,3-dicarbonyl compounds and 2-substituted acrylates
has been identified as a reliable method for the synthesis of 2,2-
mediated synthesis of hexahydrobenzofurans has not been studied.
We describe here our results in this area, together with our work on
the modification of the reaction to allow the functionalization of
the C-3 position and the preparation of other fused 2,3-dihy-
drofuran systems. Finally, we also report our studies on the trans-
formation of oxhydrindanes into several types of tetrahydroindoles.
2. Results and discussion
Cerium(IV) ammonium nitrate (CAN) is a stable, easily handled
and inexpensive reagent that has found widespread application in
synthesis8,9 mainly because of its ability to generate carbon-cen-
tered radicals, which is associated to its strong one-electron oxi-
dative properties. Due to our interest in the synthetic applications
of Ce(IV) salts,10 we undertook the study of the CAN-promoted
reaction between cyclic
b-diketones and chalcones as a,b-un-
saturated carbonyl substrates able to generate 2,3-disubstituted
2,3,4,5,6,7-hexahydrobenzofurans and hence useful for the study of
the diastereoselectivity of the radical cyclization leading to the
benzofuran skeleton. The conditions found in the literature for re-
lated examples4 failed to give any recognizable products; however,
after some optimization work, we found that slow addition of CAN
in acetonitrile at ꢀ20 ꢁC to a solution of the reactants in the same
solvent, followed by stirring at room temperature for 24 h, afforded
the expected products in good to excellent yields (Scheme 1 and
Table 1). The overall transformation involves the generation of
disubstituted 2,3,4,5,6,7-hexahydrobenzofurans5 and
a similar
reaction starting from nitrostyrenes has been applied to the prep-
aration of 2-hydroxyimino-3-substituted compounds.6 However,
* Corresponding author. Tel.: þ34 91 3941840; fax: þ34 91 3941822; e-mail
ꢀ
address: josecm@farm.ucm.es (J.C. Menendez).
y
Permanent address: Organic Chemistry Division, Central Leather Research
Institute, Adyar, Chennai, India
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.10.017

S. Maiti et al. / Tetrahedron 66 (2010) 9512e9518
9513
a CeC and a CeO bond and affords 2,3-disubstituted hexahy-
Ce3+
O
Ce4+
- H+
O
H
O
drobenzofuran derivatives bearing functional groups at the C-2 and
C-4 positions. The diastereoselectivities were also normally very
good, with most of the reactions giving trans/cis ratios higher than
10:1 and half of them giving exclusively the trans isomer. In an
effort to extend the synthetic scope of the method, we also in-
vestigated the CAN-promoted reaction between 1,3-cyclo-
pentanedione 7 and chalcones 2, which afforded compounds 3n
and 3o in good yields and with diastereoselectivities comparable to
those found for the six-membered substrates (entries 14 and 15).
This result is interesting in view of the limited availability of
methods for the preparation of cyclopenta[b]furan derivatives. In
fact, the 2,3-disubstituted 2,3,5,6-tetrahydrocyclopenta[b]furan
framework found in 3n and 3o is unknown in the literature.11
H
H
O
Ar1
Ar2
R
R
2
O
R
R
1 (n = 1)
Ar1
Ar1
O
O
O
H
O
O
Ce4+
Ce3+
Ar2
Ar2
R
R
O
R
R
5
4
- H+
Ar1
O
O
Ar2
Ar1
O
CAN (2.5 eq),
O
Ar2
O
NaHCO3 (3 eq)
R
O
3
O
+
R
R
Ar1
Ar2
R
O
- 20 °C, 1 h,
rt, 24 h
O
n
2
n
R
R
Scheme 2. Mechanistic proposal to account for the CAN-promoted synthesis of
2,3,6,7-tetrahydrobenzofuran-4(5H)-ones.
3
1
Scheme 1. CAN-promoted, trans-diastereoselective synthesis of 2,3-disubstituted
2,3,6,7-tetrahydrobenzofuran-4(5H)-one derivatives.
O
O
Table 1
Ar1
Ar2
+
Scope and yields of the synthesis of compounds 3
R
R1
O
Entry Product
n
Ar1
Ar2
R
Yield (%) dr (trans/cis)
R
6
1
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
3g
3h
3i
1
1
1
1
1
1
1
1
1
1
1
Ph
Ph
Ph
Ph
Ph
Ph
Me 82
H 81
8:1
7:1
1:0
1:0
1:0
CAN (2.5 eq), NaHCO3 (3 eq),
- 20 °C, 1 h, rt, 24 h
4-MeC6H4 Me 80
4-MeC6H4 85
Me 80
85
H
4-MeC6H4 Ph
4-MeC6H4 Ph
Ar1
O
Ar1
R1
H
1:0
R1
O
4-MeC6H4 4-MeC6H4 Me 85
4-MeC6H4 4-MeC6H4 83
Me 70
20:1
11:1
17:1
18:1
6:1
H
Ar2
O
R
9
10
11
Ph
Ph
4-ClC6H4
4-ClC6H4
4-MeC6H4
O
Ar2
R
R
3j
3k
H
H
72
65
O
4-BrC6H4
R
O
8
7
12
13
3l
1
1
Ph
H
H
81
82
1:0
1:0
Scheme 3. CAN-promoted synthesis of C3-functionalized 2,3,6,7-tetrahydrobenzofuran-
4(5H)-ones 7.
S
S
3m
4-MeC6H4
Table 2
Scope and yields of the synthesis of C3-functionalized compounds 7
14
15
3n
3O
0
0
Ph
Ph
Ph
4-MeC6H4
H
H
85
80
6:1
1:0
Entry
Product
Ar1
Ar2
R
R1
Yield (%)
dr (trans/cis)
1
2
3
4
5
7a
7b
7c
7d
7e
Ph
Ph
Ph
Ph
Ph
Ph
Ph
4-MeC6H4
4-ClC6H4
Ph
Me
H
Me
Me
Me
H
H
H
H
80
82
85
80
70
10:1
8:1
11:1
6:1
A mechanistic proposal to explain the isolation of compounds 3
is summarized in Scheme 2 and involves an initial one-electron
oxidation of the starting dicarbonyl compound 1 to generate a
C-centered radical 4, followed by its addition to chalcone 2, a sec-
ond oxidation step to generate carbocation 5 and a final cyclization.
In order to achieve functionalization also at C-3, we studied the
reaction starting from compounds with extended conjugation 6,12
which can be regarded as chalcone vinilogues. As shown in Scheme
3 and Table 2, these reactions afforded the expected 3-vinylated
products 7 in good yields, and also with good trans-diaster-
eoselectivities same for the case where R1¼Me. Interestingly, the
radical reactions starting from compounds 4 proceeded with full
regioselectivity and afforded exclusively compounds 7, with no trace
of the other potential products according to the proposed mecha-
nism, namely the fused oxepines 8.
Me
2:1
While the transformation of fused furans bearing a 2-methyl sub-
stituent into the corresponding pyrroles by reaction with primary
amines is known in the literature,15 we desired to investigate the
generalization of this result to 2-acyl derivatives, and also were in-
trigued by the possibility of carrying out a similar transformation
starting directly from our fused 2,3-dihydro systems 3. For the initial
study (Scheme 4), we first dehydrogenated compounds 3 to tetra-
hydrobenzofuran derivatives 9 by refluxing them in toluene con-
taining suspended palladium on charcoal. Subsequent treatment of
compounds9withhexylamine, usedasamodelprimaryamine, again
in refluxing toluene, afforded, as expected, the 1-hexyl-2-arylcar-
bonyl-3-aryl-4-oxo-4,5,6,7-tetrahydroindoles 10, presumably by an
ANRORC (Addition of Nucleophile, Ring-Opening and Ring-Closure)
mechanism. These compounds are of interest in themselves and also
as potential precursor to 4-hydroxyindoles through oxygen-pro-
moted dehydrogenation.12 Since we had purposefully designed the
conditions to be similar for both reactions, we attempted the one-pot
Withareliable methodfor thesynthesis of fused 2,3-dihydrofuran
derivatives in hand, we set out to study their application to the syn-
thesis of nitrogen heterocycles, which we considered of interest in
view of the biological importance of 4-hydroxyindoles13 and the
difficulties often found in their preparation by traditional methods.14

9514
S. Maiti et al. / Tetrahedron 66 (2010) 9512e9518
n-Hexylamine, (3 eq),
Ar1
Ar1
O
O
Ar2
O
Ar2
O
toluene, reflux, 1 day
R
R
O
N
R
R
5CH3
Cmpd.
10a
R
Me
H
Ar1
Ar2
Ph
Yield, %
60
Cmpd.
9a
R
Ar1
Ar2
Ph
Yield, %
60
Ph
Ph
Me
H
Ph
Ph
10b
Ph
80
9b
Ph
85
10c
H
4-MeC6H4
Ph
Ph
85
9c
H
4-MeC6H4
Ph
Ph
80
10d
H
4-MeC6H4
55*
9d
H
4-MeC6H4
85
10e
H
4-MeC6H4
70
9e
H
4-MeC6H4
45
S
S
*Overall from compound 3m
30% Pd-C, toluene,
reflux, 2 days
Ar1
O
Ar1
O
Ar1
Ar2
O
n-Hexylamine, (3 eq),
Ar2
O
Ar2
N
toluene, reflux, 1 day
R
R
Me
Me
Me
Me
O
N
[R = Me]
O
N
5
5
CH3
CH3
3
CH
5
3
11
n-Hexylamine, (3 eq),
Ar1
Ar2
4-ClC6H4
Ph
Yield, %
85
toluene, reflux, 1 day
Cmpd.
12a
Ph
Ph
[R = H]
12b
85
Ar1
O
O
Ar1
Ar1
O
Ar1
H
O
O
O
n-Hexylamine
Ar2
Ar2
- Ar2-CHO
O
O
H
O
H
N
9
13
5CH3
Yield, %
Cmpd.
14a
Ar1
4-MeC6H4 75
14b
80
S
Scheme 4. Transformation of compounds 3 into fused pyrroles 10e12.
transformation of compounds 3 into 10, but obtained only complex
mixtures.
a five-or six-membered carbocycle. These reactions, which involve
the use of very simple and inexpensive reagents, are highly diaster-
eoselective in favour of the trans diastereoisomers, and could be
designed to yield products functionalized at the C-2 and C-4 or C-
2,3,4 positions. The fused 2,3-dihydrofuran derivatives were shown
to be useful precursors for 6,7-dihydroindole-4(5H)-ones. Thus,
2-acyl-3-aryl-6,7-dihydrobenzofuran-4(5H)-ones were transformed
into 1-alkyl-2-acyl-3-aryl-6,7-dihydroindole-4(5H)-ones by 2,3-
dehydrogenation followed by reaction with primary amines. The
direct reaction of the tetrahydrobenzofuran-4(5H)-one compounds
derived from dimedone with amines was also possible and gave
1-alkyl-2-alkylimino-3-aryl-6,7-dihydroindole-4(5H)-ones, while
analogous starting materials derived from 1,3-cyclohexanedione
underwent an unprecedented 2-deacylation reaction and gave
1-alkyl-3-aryl-6,7-dihydroindole-4(5H)-ones. These processes sig-
nificantly extend the synthetic scope of the reaction between 1,3-
dicarbonyl compounds and alkenes under free-radical conditions
andthesubsequenttransformationoftheinitialbenzofuranproducts
into indole derivatives.
We next attempted the direct reaction of 2,3-dihydrofuran de-
rivatives 3 with hexylamine, and obtained the results shown in the
lower half of Scheme 4. For the case R¼Me, the observed products
were imines 12. These compounds were not observed in the re-
actions leading to 10, which shows that the reaction of the amine
with the carbonyl group in 10, which is conjugated with the elec-
tron-releasing pyrrole nitrogen atom, is not possible under the
reaction conditions. Therefore, the imine formation step can be
assumed to take place on 3 leading to intermediate 11, which would
then undergo the same reaction sequence as above, finally fur-
nishing 12. On the other hand, for starting materials where R¼H,
the final products were 3-aryltetrahydroindoles 14, lacking the
2-acyl group, which is a relevant result due to the importance of
3-arylindole frameworks.16 Loss of the 2-acyl substituent can be
rationalized as a consequence of an intramolecular hydride transfer
furnishing the highly stabilized carbocation 13, which would then
evolve to intermediates with structure 9 and a molecule of alde-
hyde Ar2CHO. Compounds 9 would then afford the observed final
products 14 by ANRORC-type reaction with the primary amine, as
described above. The difference in behaviour between the cases
R¼Me and R¼H is probably due to the fact that in the latter case
hydride shift takes place before imine formation, for reasons that
are not clearly understood at present.
3. Experimental
3.1. General
All reagents were of commercial quality (Aldrich, Fluka, SDS,
Probus) and were used as received. Solvents (from SDS) were dried
and purified using standard techniques. Reactions were monitored
by thin layer chromatography, on aluminium plates coated with
In summary and conclusion, we have shown that the CAN-pro-
moted reaction between cyclic 1,3-diketones and chalcones, affords
oxygenheterocyclescontaininga2,3-dihydrofuranfragmentfusedto

S. Maiti et al. / Tetrahedron 66 (2010) 9512e9518
9515
silica gel with fluorescent indicator (SDS CCM221254). Separations
by flash chromatography were performed on silica gel (SDS 60 ACC,
230e40 mesh). Melting points were measured with a Reichert 723
hot stage microscope, and are uncorrected. Infrared spectra were
recorded on a PerkineElmer Paragon 1000 FT-IR spectrophotom-
eter, with all compounds examined as films on a NaCl disk. NMR
spectra were obtained on a Bruker Avance instrument (250 MHz for
1H, 62.9 MHz for 13C), maintained by the Servicio de RMN, Uni-
versidad Complutense, with CDCl3 as solvent. Combustion ele-
(neat) 2947.4, 1674.9, 1639.9, 1605.6, 1394.1, 1230.7, 1177.4, 1063.9,
759.4, 699.8 cmꢀ1. 1H NMR (CDCl3, 250 MHz)
2.07e2.24 (m, 2H),
d
2.30e2.50 (m, 2H), 2.42 (s, 3H), 2.57e2.74 (m, 2H), 5.06 (dd, J¼1.0
and 6.1 Hz, 1H), 5.93 (dd, J¼1.4 and 6.1 Hz, 1H), 7.24e7.34 (m, 4H),
7.40e7.46 (m, 3H), 7.96 (dd, J¼1.6 and 8.2 Hz, 2H). 13C NMR (CDCl3,
62.9 MHz) d 21.9, 22.2, 24.5, 36.9, 54.9, 90.4, 114.7, 126.2 (2C), 129.4,
129.5 (2C), 129.6 (2C), 129.8 (2C), 134.2, 139.9, 145.1, 178.6, 194.5,
199.0. Anal. Calcd for C22H20O3: C, 79.50; H, 6.06. Found: C, 79.27;
H, 5.94.
ꢀ
mental analyses were determined by the Servicio de Microanalisis
Elemental, Universidad Complutense, using a Leco 932 CHNS
microanalyzer.
3.2.5. (ꢂ)-trans-2-Benzoyl-6,6-dimethyl-3-(4-methylphenyl)-
2,3,6,7-tetrahydrobenzofuran-4(5H)-one (3e). Light yellow viscous
liquid. IR (neat) 2958.0, 1683.1, 1640.6, 1395.6, 1216.2, 1068.5,
3.2. General procedure for the CAN-promoted synthesis of
fused 2,3-dihydrobenzofurans: preparation of compounds
(3) and (7)
963.3, 692.5 cmꢀ1. 1H NMR (CDCl3, 250 MHz)
d 1.20 (s, 3H), 1.23
(s, 3H), 2.21e2.32 (m, 2H), 2.40 (s, 3H), 2.50e2.52 (m, 2H), 5.05
(d, J¼5.7 Hz, 1H), 5.84 (d, J¼5.7 Hz, 1H), 7.17e7.25 (m, 2H), 7.21
(d, J¼3.8 Hz, 2H), 7.42e7.52 (m, 2H), 7.56e7.63 (m, 1H), 8.02 (d,
A mixture of the suitable 1,3-dicarbonyl compound 1 (1 mmol),
chalcone 2 (1 mmol) for the synthesis of 3 or vinylogous chalcone 4
for the synthesis of 5 and NaHCO3 (3 mmol) in acetonitrile (5 mL)
was cooled to ꢀ20 ꢁC. To this stirred solution was dropwise added
a solution of CAN (2.5 equiv) in acetonitrile (10 mL), over 30 min.
The reaction mixture was stirred at ꢀ20 ꢁC for 1 h and then at room
temperature for 24 h. After completion of the reaction as monitored
by TLC, the mixture was diluted with CH2Cl2 (60 mL) and washed
with water. The organic layer was dried (anhydrous Na2SO4) and
the solvent was evaporated under reduced pressure. The crude
product was purified by column chromatography on silica gel,
eluting with a petroleum ethereethyl acetate mixture (80:20, v/v).
J¼7.2 Hz, 2H). 13C NMR (CDCl3, 62.9 MHz)
d 21.7, 29.0, 29.1,
34.9, 38.4, 44.2, 54.9, 90.6, 113.2, 126.3 (2C), 128.9 (2C), 129.6
(2C), 130.2 (2C), 134.1, 136.7, 136.9, 139.6, 177.8, 194.1, 199.5.
Anal. Calcd for C24H24O3: C, 79.97; H, 6.71. Found: C, 79.65; H,
6.52.
3.2.6. (ꢂ)-trans-2-Benzoyl-3-(4-methylpheny)-2,3,6,7-tetra-hydro-
benzofuran-4(5H)-one (3f). Light yellow viscous liquid. IR (neat)
2924.3, 1682.1, 1634.2, 1393.7, 1215.7, 1176.3, 1064.1, 813.4 cmꢀ1. 1H
NMR (CDCl3, 250 MHz)
d 2.07e2.26 (m, 2H), 2.31e2.46 (m, 2H),
2.39 (s, 3H), 2.61e2.75 (m, 2H), 5.07 (d, J¼6.1 Hz, 1H), 5.88 (d,
J¼6.1 Hz, 1H), 7.18e7.29 (m, 4H), 7.42e7.48 (m, 2H), 7.56e7.62 (m,
1H), 8.03 (d, J¼8.1 Hz, 2H). 13C NMR (CDCl3, 62.9 MHz)
d 21.7, 22.0,
3.2.1. (ꢂ)-trans-2-Benzoyl-6,6-dimethyl-3-phenyl-2,3,6,7-tetrahy-
drobenzofuran-4(5H)-one (3a). Colourless solid, mp 98 ꢁC. IR (neat)
2959.1, 1684.0, 1636.3, 1395.9, 1216.3, 1069.9, 963.5, 758.5,
24.6, 36.9, 55.0, 90.5, 114.8, 126.3 (2C), 128.9 (2C), 129.6 (2C), 130.1
(2C), 134.0, 136.8, 136.9, 139.5, 178.7, 194.6, 199.6. Anal. Calcd for
C22H20O3: C, 79.50; H, 6.06. Found: C, 79.23; H, 6.19.
696.4 cmꢀ1. 1H NMR (CDCl3, 250 MHz)
d 1.19 (s, 3H), 1.22 (s, 3H),
2.29e2.30 (m, 2H), 2.51e2.53 (m, 2H), 5.05 (d, J¼5.8 Hz, 1H), 5.89
(d, J¼5.8 Hz, 1H), 7.26e7.32 (m, 2H), 7.38e7.48 (m, 5H), 7.55e7.62
(m, 1H), 8.02 (dd, J¼1.1 and 8.2 Hz, 2H). 13C NMR (CDCl3, 62.9 MHz)
3.2.7. (ꢂ)-trans-6,6-Dimethyl-2-(4-methylbenzoyl)-3-(4-methyl-
phenyl)-2,3,6,7-tetrahydrobenzofuran-4(5H)-one
(3g). Colourless
viscous liquid. IR (neat) 2959.4, 1678.8, 1641.4, 1606.5, 1395.7,
d
28.9, 29.1, 34.9, 38.3, 44.1, 54.9, 90.5, 113.2, 126.2 (2C), 128.9 (2C),
1226.5, 1182.3, 1067.7, 963.1 cmꢀ1. 1H NMR (CDCl3, 250 MHz)
d
1.19
129.5 (2C), 129.6 (3C), 134.1, 136.6, 139.9, 177.9, 194.1, 199.5. Anal.
Calcd for C23H22O3: C, 79.74; H, 6.40. Found: C, 79.53; H, 6.59.
(s, 3H), 1.22 (s, 3H), 2.22e2.37 (m, 2H), 2.39 (s, 3H), 2.41 (s, 3H),
2.49e2.51 (m, 2H), 5.02 (d, J¼5.6 Hz, 1H), 5.84 (d, J¼5.7 Hz, 1H),
7.17e7.29 (m, 6H), 7.92 (d, J¼8.3 Hz, 2H). 13C NMR (CDCl3, 62.9 MHz)
3.2.2. (ꢂ)-trans-2-Benzoyl-3-phenyl-2,3,6,7-tetrahydrobenzo-furan-
4(5H)-one (3b). Colourless solid, mp 104 ꢁC. IR (neat) 2948.2,
1682.7, 1637.8, 1448.4, 1394.4, 1215.3, 1176.1, 759.4, 692.1 cmꢀ1. 1H
d 21.7, 22.1, 29.0, 29.1, 34.9, 38.3, 44.1, 54.7, 90.5, 113.2, 126.3 (2C),
129.7 (2C), 129.8 (2C), 130.1 (2C), 134.1, 137.0, 139.4, 144.9, 177.6,
194.0, 198.9. Anal. Calcd for C25H26O3: C, 80.18; H, 7.00. Found: C,
80.11; H, 7.07.
NMR (CDCl3, 250 MHz)
d 2.09e2.21 (m, 2H), 2.33e2.46 (m, 2H),
2.62e2.74 (m, 2H), 5.07 (dd, J¼1.4 and 6.1 Hz, 1H), 5.93 (d, J¼6.2 Hz,
1H), 7.28e7.32 (m, 2H), 7.36e7.49 (m, 5H), 7.56e7.63 (m, 1H), 8.03
3.2.8. (ꢂ)-trans-2-(4-Methylbenzoyl)-3-(4-methylphenyl)-2,3,6,7-
tetrahydrobenzofuran-4(5H)-one (3h). Colourless viscous liquid. IR
(neat) 2945.7, 1678.0, 1636.0, 1606.2, 1393.8, 1230.7, 1177.0,
(dd, J¼1.1 and 8.2 Hz, 2H). 13C NMR (CDCl3, 62.9 MHz)
d 21.9, 24.5,
36.9, 55.1, 90.4, 114.8, 126.2 (2C), 128.9 (2C), 129.5 (2C), 129.6 (3C),
134.1, 136.8, 139.8, 178.7, 194.5, 199.6. Anal. Calcd for C21H18O3: C,
79.22; H, 5.70. Found: C, 79.02; H, 6.18.
811.7 cmꢀ1 1H NMR (CDCl3, 250 MHz)
. d 2.09e2.20 (m, 2H),
2.30e2.44 (m, 2H), 2.39 (s, 3H), 2.41 (s, 3H), 2.55e2.72 (m, 2H),
5.04 (d, J¼6.1 Hz, 1H), 5.87 (d, J¼6.1 Hz, 1H), 7.17e7.21 (m, 4H), 7.28
(d, J¼6.3 Hz, 2H), 7.93 (d, J¼8.2 Hz, 2H). 13C NMR (CDCl3, 62.9 MHz)
3.2.3. (ꢂ)-trans-6,6-Dimethyl-2-(4-methylbenzoyl)-3-phenyl-
2,3,6,7-tetrahydrobenzofuran-4(5H)-one (3c). Colourless viscous
liquid. IR (neat) 2960.2,1678.3,1641.5,1606.1,1396.4,1227.2,1183.9,
d
21.7, 22.0, 22.1, 24.6, 36.9, 54.9, 90.5, 114.7, 126.3 (2C), 129.6 (2C),
129.8 (2C), 130.1 (2C), 134.3, 136.9, 139.4, 144.9, 178.6, 194.6, 199.0.
Anal. Calcd for C23H22O3: C, 79.74; H, 6.40. Found: C, 79.45; H,
6.22.
1070.1, 963.7, 759.0, 699.8 cmꢀ1. 1H NMR (CDCl3, 250 MHz)
d 1.18 (s,
3H), 1.20 (s, 3H), 2.27 (d, J¼2.6 Hz, 2H), 2.39 (s, 3H), 2.50 (br s, 2H),
5.01 (d, J¼5.7 Hz, 1H), 5.86 (d, J¼5.7 Hz, 1H), 7.24e7.32 (m, 4H),
7.36e7.43 (m, 3H), 7.90 (d, J¼8.2 Hz, 2H). 13C NMR (CDCl3,
3.2.9. (ꢂ)-trans-2-Benzoyl-3-(4-chlorophenyl)-6,6-dimethyl-2,3,6,7-
tetrahydrobenzofuran-4(5H)-one (3i). Colourless viscous liquid. IR
(neat) 2958.7, 1683.8, 1652.1, 1588.9, 1397.4, 1213.2, 1091.2, 1003.1,
62.9 MHz)
d 22.1, 28.9, 29.1, 34.8, 38.3, 44.0, 54.8, 90.5, 113.2, 126.2
(2C), 129.4, 129.5 (2C), 129.7 (2C), 129.7 (2C), 134.1, 139.9, 145.1,
166.8, 194.1, 198.9. Anal. Calcd for C24H24O3: C, 79.97; H, 6.71.
Found: C, 79.62; H, 6.43.
760.5, 698.2 cmꢀ1. 1H NMR (CDCl3, 250 MHz)
d 1.20 (s, 3H), 1.21 (s,
3H), 2.28e2.29 (m, 2H), 2.51e2.53 (m, 2H), 4.99 (d, J¼5.7 Hz, 1H),
5.94 (d, J¼5.7 Hz, 1H), 7.26e7.29 (m, 2H), 7.41e7.45 (m, 5H), 7.98
3.2.4. (ꢂ)-trans-2-(4-Methylbenzoyl)-3-phenyl-2,3,6,7-tetrahy-
drobenzofuran-4(5H)-one (3d). Colourless solid, mp 202e204 ꢁC. IR
(dd, J¼1.9 and 8.3 Hz, 2H). 13C NMR (CDCl3, 62.9 MHz)
d 29.0, 29.1,
34.9, 38.3, 51.4, 55.0, 90.4, 113.0, 126.1 (2C), 129.3 (2C), 129.6 (3C),

9516
S. Maiti et al. / Tetrahedron 66 (2010) 9512e9518
130.1 (2C), 135.0, 139.8, 140.7, 177.9, 193.9, 198.4. Anal. Calcd for
C23H21ClO3: C, 72.53; H, 5.56. Found: C, 72.31; H, 5.31.
130.1 (2C), 133.3, 139.6, 145.5, 195.2, 195.8, 196.1. Anal. Calcd for
21H18O3: C, 79.22; H, 5.70. Found: C, 78.92; H, 5.61.
C
3.2.10. (ꢂ)-trans-2-Benzoyl-3-(4-chlorophenyl)-2,3,6,7-tetrahy-
drobenzofuran-4(5H)-one (3j). Colourless viscous liquid. IR (neat)
2947.4, 1679.5, 1636.7, 1588.0, 1394.9, 1213.2, 1174.6, 1090.8, 760.4,
3.2.16. (ꢂ)-trans-2-Benzoyl-6,6-dimethyl-3-styryl-2,3,6,7-tetrahy-
drobenzofuran-4(5H)-one (7a). Colourless viscous liquid. IR (neat)
2958.9, 1684.0, 1652.8, 1635.9, 1558.5, 1540.3, 1506.8, 1396.5,
699.6 cmꢀ1
.
1H NMR (CDCl3, 250 MHz)
d
2.07e2.23 (m, 2H),
1223.6 cmꢀ1. 1H NMR (CDCl3, 250 MHz)
d 1.19 (s, 3H), 1.22 (s, 3H),
2.36e2.43 (m, 2H), 2.57e2.69 (m, 2H), 5.01 (dd, J¼1.3 and 6.1 Hz,
2.29 (br s, 2H), 2.48 (br s, 2H), 4.90 (d, J¼5.1 Hz, 1H), 5.51 (dd, J¼5.3
and 7.9 Hz, 1H), 6.35 (dd, J¼7.9 and 15.8 Hz, 1H), 6.67 (d, J¼15.8 Hz,
1H), 7.29e7.65(m, 8H), 8.11 (d, J¼8.3 Hz, 2H). 13C NMR (CDCl3,
1H), 5.96 (d, J¼6.1 Hz, 1H), 7.25e7.30 (m, 2H), 7.37e7.45 (m, 5H),
8.01 (dd, J¼1.9 and 6.8 Hz, 2H). 13C NMR (CDCl3, 62.9 MHz)
d 21.9,
24.5, 36.9, 55.2, 90.4, 114.6, 126.1 (2C), 129.2 (2C), 129.5 (3C), 130.1
(2C), 135.1, 139.7, 140.7, 178.9, 194.5, 198.6. Anal. Calcd for
C21H17ClO3: C, 71.49; H, 4.86. Found: C, 71.27; H, 4.71.
62.9 MHz) d 28.8, 29.3, 34.8, 38.4, 51.3, 52.9, 89.9, 113.1, 125.8, 127.3
(2C), 129.0 (2C), 129.1, 129.2 (2C), 129.6 (2C), 134.1, 134.6, 135.8,
136.6, 177.5, 194.1, 198.9. Anal. Calcd for C25H24O3: C, 80.62; H, 6.49.
Found: C, 80.32; H, 6.28.
3.2.11. (ꢂ)-trans-3-(4-Bromophenyl)-2-(4-chlorobenzoyl)-2,3,6,7-
tetrahydrobenzofuran-4(5H)-one (3k). Colourless viscous liquid. IR
(neat) 2946.6, 1677.9, 1640.7, 1606.2, 1488.0, 1391.3, 1230.4, 1177.2,
3.2.17. (ꢂ)-trans-2-Benzoyl-3-styryl-2,3,6,7-tetrahydro-benzofuran-
4(5H)-one (7b). Colourless viscous liquid. IR (neat) 2947.3, 1678.9,
1640.9, 1596.7, 1448.9, 1396.1, 1231.6, 1178.4, 914.4, 691.7 cmꢀ1. 1H
1070.9, 1010.5 cmꢀ1. 1H NMR (CDCl3, 250 MHz)
d 2.07e2.18 (m, 2H),
2.29e2.47 (m, 2H), 2.43 (s, 3H), 2.54e2.76 (m, 2H), 4.98 (d, J¼6.1 Hz,
1H), 5.89 (d, J¼6.2 Hz,1H), 7.15 (d, J¼8.5 Hz, 2H), 7.27 (d, J¼8.4 Hz, 2H),
7.53 (d, J¼8.9 Hz, 2H), 7.93 (d, J¼8.3 Hz, 2H). 13C NMR (CDCl3,
NMR (CDCl3, 250 MHz) d 2.07e2.18 (m, 2H), 2.36e2.43 (m, 2H),
2.57e2.64 (m, 2H), 4.92 (d, J¼5.5 Hz, 1H), 5.54 (dd, J¼5.6 and 7.9 Hz,
1H), 6.35(dd, J¼7.9and15.8Hz,1H), 6.67(d, J¼15.8Hz,1H), 7.29e7.64
(m, 8H), 8.12 (dd, J¼1.5 and 8.1 Hz, 2H). 13C NMR (CDCl3, 62.9 MHz)
62.9 MHz)
d 21.9, 22.2, 24.5, 36.9, 54.9, 89.6, 114.7, 123.4, 127.8 (2C),
129.7 (2C),129.8 (2C),132.6 (2C),134.1,138.9,145.2,178.4,194.5,198.8.
Anal. Calcd for C22H19BrO3: C, 64.25; H, 4.66. Found: C, 63.98; H, 4.42.
d 21.9, 24.6, 36.9, 53.0, 89.9, 114.6, 125.8, 127.3 (2C), 129.0 (2C), 129.1,
129.2 (2C), 129.6 (2C), 134.1, 134.7, 135.8, 136.7, 178.6, 194.7, 199.1.
Anal. Calcd for C23H20O3: C, 80.21; H, 5.85. Found: C, 79.96; H, 6.04.
3.2.12. (ꢂ)-trans-2-Benzoyl-3-(2-thienyl)-2,3,6,7-tetrahydro-benzo-
furan-4(5H)-one (3l). Pale brown crystals, mp 132 ꢁC
(EtOAcehexane). IR (neat) 2948.7, 1683.7, 1635.5, 1448.1, 1394.4,
3.2.18. (ꢂ)-trans-6,6-Dimethyl-2-(4-methylbenzoyl)-3-styryl-
2,3,6,7-tetrahydrobenzofuran-4(5H)-one (7c). Colourless viscous
liquid. IR (neat) 2957.9,1678.6,1640.4,1606.2,1397.1,1224.5,1182.6,
1229.2, 1181.3, 912.5 cmꢀ1. 1H NMR (CDCl3, 250 MHz)
d 2.04e2.23
(m, 2H), 2.29e2.44 (m, 2H), 2.47e2.70 (m, 2H), 5.19 (dd, J¼1.3 and
5.7 Hz, 1H), 6.16 (d, J¼5.8 Hz, 1H), 7.00e7.04 (m, 1H), 7.09e7.11 (m,
1H), 7.37e7.39 (m, 1H), 7.44e7.50 (m, 2H), 7.56e7.63 (m, 1H), 8.07
968.2, 693.3 cmꢀ1. 1H NMR (CDCl3, 250 MHz)
d 1.18 (s, 3H), 1.22 (s,
3H), 2.29 (br s, 2H), 2.44 (s, 3H), 2.47 (br s, 2H), 4.88 (d, J¼5.1 Hz,
1H), 5.51 (dd, J¼5.2 and 7.9 Hz, 1H), 6.35 (dd, J¼7.9 and 15.8 Hz, 1H),
6.67 (d, J¼15.8 Hz, 1H), 7.28e7.46 (m, 7H), 8.01 (d, J¼8.2 Hz, 2H). 13C
(dd, J¼1.5 and 8.2 Hz, 2H). 13C NMR (CDCl3, 62.9 MHz)
d 21.9, 24.6,
36.9, 55.1, 85.9, 114.6, 127.0, 127.3, 127.5, 128.9 (2C), 129.6 (2C),
134.2, 136.6, 142.0, 177.9, 194.5, 198.9. Anal. Calcd for C19H16SO3: C,
70.35; H, 4.97; S, 9.88. Found: C, 70.05; H, 4.94; S, 9.79.
NMR (CDCl3, 62.9 MHz) d 22.2, 28.8, 29.3, 34.8, 38.4, 51.3, 52.7, 89.9,
113.0, 125.9, 127.3 (3C), 129.1, 129.2 (2C), 129.7 (3C), 134.0, 134.5,
135.8, 145.1, 177.4, 194.1, 198.4. Anal. Calcd for C26H26O3: C, 80.80; H,
6.78. Found: C, 80.65; H, 6.38.
3.2.13. (ꢂ)-trans-2-(4-Methylbenzoyl)-3-(2-thienyl)-2,3,6,7-tetrahy-
drobenzofuran-4(5H)-one (3m). Light yellow viscous liquid. IR
(neat) 2949.3, 1677.1, 1634.3, 1606.1, 1394.0, 1229.0, 1182.2, 1064.3,
3.2.19. (ꢂ)-trans-2-(4-Chlorobenzoyl)-6,6-dimethyl-3-styryl-2,3,6,7-
tetrahydrobenzofuran-4(5H)-one (7d). White crystals, mp 120 ꢁC
(EtOAcehexane). IR (neat) 2959.3, 1682.0, 1636.4, 1588.5, 1399.5,
709.8 cmꢀ1 1H NMR (CDCl3, 250 MHz)
. d 1.99e2.21 (m, 2H),
2.36e2.49 (m, 2H), 2.41 (s, 3H), 2.52e2.69 (m, 2H), 5.17 (d, J¼5.7 Hz,
1H), 6.16 (d, J¼5.7 Hz, 1H), 7.00e7.03 (m, 1H), 7.09e7.11 (m, 1H),
7.26 (d, J¼8.0 Hz, 2H), 7.37 (d, J¼5.0 Hz, 1H), 8.00 (d, J¼8.2 Hz, 2H).
1225.6, 1091.8, 965.0 cmꢀ1. 1H NMR (CDCl3, 250 MHz)
d 1.17 (s, 3H),
1.18 (s, 3H), 2.26 (br s, 2H), 2.46 (s, 2H), 4.85 (d, J¼5.2 Hz, 1H), 5.55
(dd, J¼5.3 and 7.9 Hz, 1H), 6.32 (dd, J¼7.9 and 15.8 Hz, 1H), 6.67 (d,
J¼15.8 Hz, 1H), 7.29e7.47 (m, 7H), 8.07 (d, J¼8.5 Hz, 2H). 13C NMR
13C NMR (CDCl3, 62.9 MHz)
d 21.9, 22.2, 24.6, 36.9, 54.9, 85.5, 114.5,
126.9, 127.2, 127.5, 129.7 (2C), 129.8 (2C), 134.0, 142.2, 145.2, 177.9,
194.5, 198.3. Anal. Calcd for C20H18SO3: C, 70.98; H, 5.36; S, 9.47.
Found: C, 70.73; H, 5.12; S, 9.21.
(CDCl3, 62.9 MHz) d 28.8, 29.3, 34.8, 38.4, 44.1, 52.9, 89.9, 112.9,
125.7, 127.3 (2C), 129.2 (3C), 129.3 (2C), 131.0 (2C), 134.7, 134.9,
135.7, 140.6, 177.7, 194.1, 197.9. Anal. Calcd for C25H23ClO3: C, 73.79;
H, 5.70. Found: C, 69.56; H, 5.90.
3.2.14. 2-Benzoyl-3-phenyl-5,6-dihydro-2H-cyclopenta[b]furan-4
(3H)-one (3n). Colourless viscous liquid. IR (neat) 2924.8, 1684.5,
3.2.20. (ꢂ)-trans-2-Benzoyl-6,6-dimethyl-3-(1-methyl-2-phenyl-
vinyl)-2,3,6,7-tetrahydrobenzofuran-4(5H)-one (7e). Colourless vis-
cous liquid. IR (neat) 2960.4, 1643.4, 1394.8, 1287.8, 1221.8, 1028.8,
1626.0, 1448.2, 1400.5, 1242.7, 755.7, 690.7 cmꢀ1 1H NMR (CDCl3,
.
250 MHz)
1H), 6.86 (d, J¼5.5 Hz, 1H), 7.29e7.66 (m, 8H), 8.17 (dd, J¼1.4 and
6.9 Hz, 2H). 13C NMR (CDCl3, 62.9 MHz)
22.7, 41.2, 54.5, 98.2, 119.8,
d 2.72e2.76 (m, 2H), 2.85e2.89 (m, 2H), 4.83e4.87 (m,
700.3 cmꢀ1. 1H NMR (CDCl3, 250 MHz)
d 1.22 (s, 3H), 1.26 (s, 3H),
d
1.67 (s, 3H), 2.32 (s, 2H), 2.52e2.57 (m, 2H), 4.24 (s, 1H), 6.24 (d,
J¼15.9 Hz,1H), 6.67 (d, J¼15.9 Hz, 1H), 7.06e7.09 (m, 2H), 7.27e7.54
126.1 (2C), 128.9 (2C), 129.5 (2C), 129.7, 129.9 (2C), 134.5, 135.8,
139.5, 195.1, 196.1, 196.3. Anal. Calcd for C20H16O3: C, 78.93; H, 5.30.
Found: C, 78.64; H, 5.17.
(m, 8H). 13C NMR (CDCl3, 62.9 MHz)
d 28.2, 29.1, 29.5, 34.6, 38.5,
51.6, 56.3, 94.3, 115.1, 125.7, 127.9, 128.7 (2C), 128.8 (2C), 129.1 (2C),
129.2 (2C), 132.9, 137.5, 138.6, 147.9, 175.4, 192.8, 194.6. Anal. Calcd
for C26H26O3: C, 80.80; H, 6.78. Found: C, 80.54; H, 6.56.
3.2.15. 2-(4-Methylbenzoyl)-3-phenyl-5,6-dihydro-2H-cyclopenta[b]-
furan-4(3H)-one (3o). Colourless viscous liquid. IR (neat) 2925.4,
1681.5, 1626.2, 1606.3, 1400.6, 1243.3, 1180.2, 847.8, 754.9,
3.3. General procedure for the dehydrogenation of (3):
synthesis of compounds (9)
699.1 cmꢀ1. 1H NMR (CDCl3, 250 MHz)
d 2.44 (s, 3H), 2.73e2.75 (m,
2H), 2.85e2.87 (m, 2H), 4.82 (d, J¼5.3 Hz,1H), 6.85 (d, J¼5.4 Hz,1H),
7.29e7.42 (m, 7H), 8.07 (d, J¼8.1 Hz, 2H). 13C NMR (CDCl3, 62.9 MHz)
The suitable compound 3 (1 mmol) was dissolved in dry toluene
(20 mL) and PdeC (30%, 1 mmol) was added. The suspension was
d
22.3, 22.7, 41.3, 54.4, 89.1, 119.9, 126.2 (2C), 129.6 (3C), 129.7 (2C),

S. Maiti et al. / Tetrahedron 66 (2010) 9512e9518
9517
refluxed for 2 days. After completion of the reaction, the mixture
was filtered through Celite, which was washed with CH2Cl2
(20 mL), and the solvent was evaporated under reduced pressure.
Pure compounds 11 were obtained by column chromatography on
silica gel, eluting with a petroleum ethereethyl acetate mixture
(85:15, v/v).
reaction products were obtained by a column chromatography on
silica gel, eluting with a petroleum ethereethyl acetate mixture
(85:15, v/v).
3.4.1. 2-Benzoyl-1-(n-hexyl)-6,6-dimethyl-3-phenyl-6,7-dihy-
droindol-4(5H)-one (10a). Colourless viscous liquid. IR (neat)
2929.3, 1682.3, 1489.8, 1434.9, 1334.7, 1054.2, 767.5, 691.1 cmꢀ1. 1H
3.3.1. 2-Benzoyl-6,6-dimethyl-3-phenyl-6,7-dihydro-benzofuran-4
NMR (CDCl3, 250 MHz) d 0.84e0.88 (m, 3H), 1.22 (s, 3H), 1.23 (s,
(5H)-one (9a). Colourless solid, mp 145 ꢁC. IR (neat) 2960.0, 1681.7,
3H), 1.13e1.31 (m, 6H), 1.66e1.71 (m, 2H), 2.39 (d, J¼2.0 Hz, 2H),
2.93 (d, J¼1.5 Hz, 2H), 3.41 (dt, J¼1.2 and 7.1 Hz, 2H), 7.28e7.37 (m,
6H), 7.60e7.64 (m, 2H), 7.77e7.82 (m, 2H). 13C NMR (CDCl3,
1448.9, 1332.8, 1227.0, 1053.3, 894.3, 767.7 cmꢀ1 1H NMR (CDCl3,
.
250 MHz)
7.41e7.47 (m, 2H), 7.54e7.63 (m, 3H), 7.92e7.95 (m, 2H). 13C NMR
(CDCl3, 62.9 MHz) 29.0 (2C), 35.8, 37.8, 52.4,117.7,121.7,126.2 (2C),
d 1.24 (s, 6H), 2.39 (s, 2H), 2.92 (s, 2H), 7.29e7.36 (m, 3H),
62.9 MHz)
d 14.5, 23.0, 27.8, 28.8, 29.3, 30.9, 32.1, 35.7, 38.0, 52.6,
d
54.9, 113.4, 121.1, 124.8 (2C), 127.9 (2C), 128.7 (2C), 129.3 (2C),
129.8, 130.3, 131.5, 139.2, 149.6, 160.9, 165.8, 192.6. Anal. Calcd for
C29H33NO2: C, 81.46; H, 7.78; N, 3.28. Found: C, 81.23; H, 7.67;
N, 3.12.
129.1 (2C), 129.1 (2C), 129.2, 129.3, 129.8 (2C), 134.1, 137.7, 152.3,
165.3, 192.5, 192.9. Anal. Calcd for C23H20O3: C, 80.21; H, 5.85.
Found: C, 79.93; H, 5.76.
3.3.2. 2-Benzoyl-3-phenyl-6,7-dihydrobenzofuran-4(5H)-one
(9b). Colourless solid, mp 175 ꢁC. IR (neat) 3061.5, 2952.9, 1681.7,
1493.0, 1448.9, 1331.9, 1227.8, 1011.5, 692.1 cmꢀ1. 1H NMR (CDCl3,
3.4.2. 2-Benzoyl-1-(n-hexyl)-3-phenyl-6,7-dihydroindol-4(5H)-one
(10b). Colourless viscous liquid. IR (neat) 2956.9, 2929.8, 1674.5,
1651.9, 1488.9, 1470.3, 1367.1, 1122.2, 701.2 cmꢀ1 1H NMR (CDCl3,
.
250 MHz)
J¼6.3 Hz, 2H), 7.29e7.36 (m, 3H), 7.40e7.49 (m, 3H), 7.53e7.62 (m,
3H), 7.93e7.97 (m,1H). 13C NMR (CDCl3, 62.9 MHz)
22.8, 23.8, 38.1,
117.8, 122.9, 126.2 (2C), 129.0 (2C), 129.2 (2C), 129.3, 129.5, 129.6,
129.9 (2C), 134.1, 137.6, 151.8, 166.2, 193.1. Anal. Calcd for C21H16O3:
C, 79.73; H, 5.10. Found: C, 79.45; H, 4.97.
d
2.24e2.32 (m, 2H), 2.51 (d, J¼6.0 Hz, 2H), 3.05 (d,
250 MHz)
d
0.85 (t, J¼6.4 Hz, 3H), 1.19e1.32 (m, 6H), 1.61e1.69 (m,
2H), 2.23e2.29 (m, 2H), 2.49 (t, J¼6.0 Hz, 2H), 3.07 (t, J¼6.2 Hz, 2H),
3.37 (dt, J¼2.1 and 6.9 Hz, 2H), 7.29e7.36 (m, 6H), 7.60e7.64 (m,
d
2H), 7.76e7.79 (m, 2H). 13C NMR (CDCl3, 62.9 MHz)
d 14.5, 22.8,
22.9, 24.0, 27.7, 30.9, 32.1, 38.3, 54.8, 113.5, 122.2, 124.9 (2C), 127.9
(2C), 128.6 (2C), 128.7, 129.3 (2C), 129.8, 130.3, 139.2, 149.2, 161.0,
166.8, 193.3. Anal. Calcd for C27H29NO2: C, 81.17; H, 7.32; N, 3.51.
Found: C, 79.98; H, 7.19; N, 3.32.
3.3.3. 2-Benzoyl-3-(4-methylphenyl)-6,7-dihydrobenzofuran-4(5H)-
one (9c). Colourless viscous liquid. IR (neat) 2954.0, 1681.6, 1506.0,
1450.1,1332.4,1227.9, 1011.9, 893.3 cmꢀ1. 1H NMR (CDCl3, 250 MHz)
3.4.3. 2-Benzoyl-1-(n-hexyl)-3-(4-methylphenyl)-6,7-dihydro-indol-
4(5H)-one (10c). Colourless viscous liquid. IR (neat) 2926.9, 2855.7,
1683.2, 1506.1, 1428.8, 1332.2, 1061.6, 1010.4, 819.6 cmꢀ1. 1H NMR
d
2.20e2.30 (m, 2H), 2.32 (s, 3H), 2.50 (t, J¼6.1 Hz, 2H), 3.05 (t,
J¼6.2 Hz, 2H), 7.12 (d, J¼8.1 Hz, 2H), 7.39e7.63 (m, 5H), 7.95 (d,
J¼8.1 Hz, 2H). 13C NMR (CDCl3, 62.9 MHz)
d
21.7, 22.8, 23.8, 38.1,
(CDCl3, 250 MHz)
d
0.86 (t, J¼6.5 Hz, 3H), 1.16e1.37 (m, 6H),
122.8, 126.2 (2C), 126.4, 128.9, 128.9 (2C), 129.8 (2C), 129.9 (2C),
130.6,134.1,139.5,152.1,166.1,193.1,193.3. Anal. Calcd for C22H18O3:
C, 79.98; H, 5.49. Found: C, 79.78; H, 5.32.
1.63e1.74 (m, 2H), 2.19e2.29 (m, 2H), 2.33 (s, 3H), 2.48 (t, J¼5.9 Hz,
2H), 3.05 (t, J¼6.2 Hz, 2H), 3.37e3.43 (m, 2H), 7.12 (d, J¼8.1 Hz, 2H),
7.31e7.36 (m, 3H), 7.52 (d, J¼8.2 Hz, 2H), 7.76e7.80 (m, 2H). 13C
NMR (CDCl3, 62.9 MHz) d 14.5, 21.7, 22.9, 23.0, 24.0, 27.7, 30.9, 32.1,
3.3.4. 2-(4-Methylbenzoyl)-3-phenyl-6,7-dihydrobenzofuran-4(5H)-
one (9d). White solid, mp 195 ꢁC. IR (neat) 2950.6, 1682.1, 1604.4,
1491.6, 1430.4, 1331.3, 1230.1, 1175.9, 1011.2, 896.2, 768.6 cmꢀ1. 1H
38.3, 54.8, 122.1, 124.8 (2C), 127.1, 127.9 (2C), 128.7 (2C), 129.9 (2C),
130.2, 138.8, 139.3, 149.1, 149.4, 161.2, 166.5, 193.4. Anal. Calcd for
C28H31NO2: C, 81.32; H, 7.56; N, 3.39. Found: C, 81.13; H, 7.32;
N, 3.19.
NMR (CDCl3, 250 MHz)
d
2.25 (t, J¼6.3 Hz, 2H), 2.41 (s, 3H),
2.49e2.54 (m, 2H), 3.05 (t, J¼6.3 Hz, 2H), 7.22e7.37 (m, 5H),
7.56e7.61 (m, 2H), 7.85 (d, J¼8.2 Hz, 2H). 13C NMR (CDCl3,
3.4.4. 1-(n-Hexyl)-6,6-dimethyl-2-(4-methylbenzoyl)-3-phenyl-6,7-
dihydro-indol-4(5H)-one (10d). Colourless viscous liquid. IR (neat)
2957.4, 2928.9, 1682.4, 1606.3, 1435.4, 1333.1, 1054.5, 766.9,
62.9 MHz) d 19.9, 20.5, 21.5, 35.7, 115.6, 120.5, 123.8 (2C), 126.7 (2C),
126.8, 126.9, 127.4 (2C), 127.7 (2C), 132.8, 142.7, 149.2, 163.7, 190.3,
190.7. Anal. Calcd for C22H18O3: C, 79.98; H, 5.49. Found: C, 79.69; H,
5.30.
692.0 cmꢀ1. 1H NMR (CDCl3, 250 MHz)
d
0.84 (t, J¼7.1 Hz, 3H), 1.21
(s, 3H), 1.22 (s, 3H), 1.24e1.34 (m, 6H), 1.61e1.69 (m, 2H), 2.35 (s,
3H), 2.37 (s, 2H), 2.93 (m, 2H), 3.39 (t, J¼7.1 Hz, 2H), 7.15 (d,
J¼8.0 Hz, 2H), 7.26e7.35 (m, 3H), 7.61e7.64 (m, 2H), 7.68 (d,
3.3.5.
4(5H)-one (9e). Off-white solid, mp 197 ꢁC. IR (neat) 2952.3, 1681.8,
1605.5, 1410.1, 1233.5, 1177.9, 1011.9, 835.4, 709.0 cmꢀ1 1H NMR
(CDCl3, 250 MHz)
2-(4-Methylbenzoyl)-3-(2-thienyl)-6,7-dihydro-benzofuran-
J¼7.9 Hz, 2H). 13C NMR (CDCl3, 62.9 MHz)
d 14.5, 21.8, 23.0, 27.8,
.
28.7, 29.3, 30.9, 32.1, 35.6, 38.0, 52.6, 54.7, 113.5, 121.1, 124.8 (2C),
127.8 (2C), 128.6, 129.2 (2C), 129.5 (2C), 129.9, 136.5, 140.3, 149.5,
160.8, 165.8, 192.6. Anal. Calcd for C30H35NO2: C, 81.59; H, 7.99; N,
3.17. Found: C, 81.31; H, 7.84; N, 2.98.
d
2.20e2.33 (m, 2H), 2.42 (s, 3H), 2.51 (t, J¼6.0 Hz,
2H), 3.03 (t, J¼6.3 Hz, 2H), 6.98e7.01 (m, 1H), 7.26 (d, J¼7.9 Hz, 2H),
7.29e7.35 (m, 2H), 7.82 (d, J¼8.2 Hz, 2H). 13C NMR (CDCl3,
62.9 MHz)
d 22.2, 22.7, 23.8, 38.1, 116.9, 122.6, 126.8, 127.3, 128.1,
129.7 (2C), 129.9 (2C), 130.9, 135.3, 144.9, 148.5, 165.8, 191.5, 192.9.
Anal. Calcd for C20H16O3S: C, 71.41; H, 4.79. Found: C, 71.28; H, 4.65.
3.4.5. 1-(n-Hexyl)-2-(4-methylbenzoyl)-3-phenyl-6,7-dihydro-indol-
4(5H)-one (10e). Colourless viscous liquid. IR (neat) 2929.4,
2857.0, 1681.7, 1606.4, 1492.4, 1453.7, 1428.4, 1412.0, 1332.5,
3.4. General procedure for the reaction between benzofuran
derivatives and primary amines. Synthesis of compounds (10),
(12) and (14)
1177.8, 1062.2, 1011.0 cmꢀ1 1H NMR (CDCl3, 250 MHz)
. d 0.86 (t,
J¼6.4 Hz, 3H), 1.18e1.31 (m, 6H), 1.67 (t, J¼6.4 Hz, 2H), 2.25 (t,
J¼6.2 Hz, 2H), 2.35 (s, 3H), 2.48 (t, J¼5.6 Hz, 2H), 3.06 (t, J¼5.7 Hz,
2H), 3.36e3.42 (m, 2H), 7.15 (d, J¼7.9 Hz, 2H), 7.23e7.35 (m, 3H),
7.62e7.65 (m, 2H), 7.69 (d, J¼8.1 Hz, 2H). 13C NMR (CDCl3,
The suitable compound 3 or 9 (1 mmol) was dissolved in dry
toluene (20 mL) and hexylamine (3 mmol) was added. The re-
action mixture was refluxed for 24 h. After completion of the re-
action, the solvent was evaporated under reduced pressure. Pure
62.9 MHz)
d 14.5, 21.8, 22.9, 23.0, 24.1, 27.7, 30.9, 32.1, 38.3, 54.7,
113.7, 122.2, 124.9 (2C), 127.9 (2C), 128.7, 129.3 (2C), 129.5 (2C),
129.9, 136.5, 140.3, 149.1, 160.9, 166.7, 193.3. Anal. Calcd for

9518
S. Maiti et al. / Tetrahedron 66 (2010) 9512e9518
C28H31NO2: C, 81.32; H, 7.56; N, 3.39. Found: C, 81.19; H, 7.31;
N, 3.21.
UCM Program for Distinguished Academic Visitors, which is also
gratefully acknowledged.
3.4.6. 2-[(4-Chlorophenyl)(n-hexylimino)]methyl-1-(n-hexyl)-3-phe-
nyl-6,7-dihydro-indol-4(5H)-one (12a). Colourless viscous liquid. IR
(neat) 2927.3, 2855.9, 1661.1, 1486.1, 1455.5, 1373.7, 1089.3, 1014.0,
Supplementary data
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2010.10.017. These data in-
clude MOL files and InChiKeys of the most important compounds
described in this article.
700.7 cmꢀ1. 1H NMR (CDCl3, 250 MHz)
d 0.88 (br s, 6H), 1.18e1.58
(m, 20H), 2.21e2.26 (m, 2H), 2.44e2.46 (m, 2H), 2.81e2.91 (m, 2H),
3.00e3.11 (m, 1H), 3.25e3.35 (m, 1H), 3.79e4.02 (m, 2H), 7.13e7.29
(m, 5H), 7.23 (d, J¼8.4 Hz, 2H), 7.58 (d, J¼8.2 Hz, 2H). 13C NMR
(CDCl3, 62.9 MHz) d 14.4, 14.6, 22.9, 23.0, 23.1, 24.1, 26.8, 28.0, 29.0,
References and notes
29.7, 30.9, 31.0, 31.9, 32.3, 38.7, 45.1, 54.9, 115.8, 119.3, 128.4 (2C),
128.7, 129.0 (2C), 129.3 (2C), 129.8 (2C), 131.3, 133.0, 135.2, 140.1,
144.1, 162.0, 193.0. Anal. Calcd for C35H45ClN2O: C, 77.10; H, 8.32;
N, 5.14. Found: C, 76.89; H, 8.15; N, 4.98.
1. Forselected reviews on benzofuran synthesis, see: (a) Cagniant, P.; Cagniant, D. Adv.
Heterocycl. Chem. 1975, 18, 337; (b) Donnelly, D. M. X.; Meegan, M. J. In Compre-
hensive Heterocyclic Chemistry; Katritzky, A. R., Rees, C. W., Eds.; Pergamon: Oxford,
ꢀ
1984; Vol. 4, p 657; (c) Kadieva, M. G.; Oganesyan, E. T. Chem. Heterocycl. Comp.1997,
33, 1245; (d) Gilchrist, T. L. J. Chem. Soc., Perkin Trans. 1 2001, 2491; (e) Hou, X.-L.;
Yang, Z.; Wong, H. N. C. Prog. Heterocycl. Chem. 2002, 14, 139;
(f) Horton, D. A.;Bourne, G. T.;Smythe, M. L. Chem. Rev. 2003,103, 893; (g) Graening,
T.; Thrun, F. In Comprehensive Heterocyclic Chemistry III; Katritzky, A. R., Ramsden, C.
A., Scriven, E. F. V., Taylor, R. J. K., Eds.; Elsevier: Oxford, 2008; Vol. 3, p 497; (h) De
Luca, L.; Nieddu, G.; Porcheddu, A.; Giacomelli, G. Curr. Med. Chem. 2009, 16, 1.
2. (a) Iqbal, J.; Bhatia, B.; Nayyar, N. K. Chem. Rev. 1994, 94, 519; (b) Snider, B. Chem.
Rev. 1996, 96, 339.
3. (a) Wang, Q.-F.; Hou, H.; Yao, C.-G. J. Org. Chem. 2009, 74, 7403; (b) For a general
review on the synthesis of cyclic frameworks that deals partially with this
problem, see: Singh, V.; Batra, S. Tetrahedron 2008, 64, 4511.
4. Nair, V.; Mathew, J.; Radhakrishnan, K. V. J. Chem. Soc., Perkin Trans. 11996, 1487.
5. Lee, Y. R.; Kim, B. S.; Kim, D. H. Tetrahedron 2000, 56, 8845.
6. (a) Ishikawa, T.; Miyakara, T.; Asakura, M.; Higuchi, S.; Miyauchi, Y.; Saito, S. Org.
Lett. 2005, 7, 1211; (b) Barange, D. K.; Raju, B. R.; Kavala, V.; Kuo, C.-W.; Tu, Y.-C.;
Yao, C.-F. Tetrahedron 2010, 66, 3754.
7. (a) Savitha, G.; Niveditha, S. K.; Muralidharan, D.; Perumal, P. T. Tetrahedron Lett.
2007, 48, 2943; (b) Savitha, G.; Sudhakar, R.; Perumal, P. T. Tetrahedron Lett.
2008, 49, 7260.
8. For some general reviews of cerium ammonium nitrate-promoted synthetic
transformations, see: (a) Nair, V.; Matthew, J.; Prabhakaran, J. Chem. Soc. Rev.
1997, 127; (b) Hwu, J. R.; King, K.-Y. Curr. Sci. 2001, 81, 1043; (c) Nair, V.; Pan-
icker, S. B.; Nair, L. G.; George, T. G.; Augustine, Z. Synlett 2003, 156; (d) Nair, V.;
Balagopal, L.; Rajan, R.; Mathew, J. Acc. Chem. Res. 2004, 37, 21; (e) Nair, V.;
Deepthi, A. Chem. Rev. 2007, 107, 1862.
3.4.7. 1-(n-Hexyl)-2-[(n-hexylimino)(phenyl)]methyl-3-phenyl-6,7-
dihydro-indol-4(5H)-one (12b). Colourless viscous liquid. IR (neat)
2956.2, 2928.8, 2857.1, 1660.8, 1487.7, 1446.2, 1367.9, 768.2,
694.7 cmꢀ1 1H NMR (CDCl3, 250 MHz)
. d 0.81e0.89 (m, 6H),
1.17e1.54 (m, 22H), 2.34 (s, 2H), 2.76 (s, 2H), 3.05e3.16 (m, 1H),
3.29e3.39 (m, 1H), 3.82e4.0 (m, 2H), 7.12e7.26 (m, 8H), 7.62e7.66
(m, 2H). 13C NMR (CDCl3, 62.9 MHz)
d 14.3, 14.6, 22.8, 23.1, 26.4,
27.8, 29.1, 29.2, 30.9, 31.0, 31.5, 32.2, 35.8, 37.0, 44.8, 52.6, 54.8,
116.1, 118.3, 127.9 (2C), 128.1 (2C), 128.4, 128.9 (2C), 129.3, 129.8
(2C), 131.6, 133.0, 141.7, 142.9, 163.1, 192.2. Anal. Calcd for
C35H46N2O: C, 82.30; H, 9.08; N, 5.48. Found: C, 82.01; H, 9.22;
N, 5.31.
3.4.8. 1-(n-Hexyl)-3-(4-methylphenyl)-6,7-dihydro-indol-4(5H)-one
(14a). Colourless viscous liquid. IR (neat) 2928.0, 2857.8, 1659.5,
1475.6, 1414.0, 1171.5, 825.2, 806.8 cmꢀ1. 1H NMR (CDCl3, 250 MHz)
d
0.85 (t, J¼6.6 Hz, 3H), 1.18e1.28 (m, 6H), 1.56 (br s, 2H), 2.20e2.28
(m, 2H), 2.42 (s, 3H), 2.54 (t, J¼5.8 Hz, 2H), 2.85 (t, J¼6.0 Hz, 2H),
3.87 (t, J¼7.5 Hz, 2H), 6.54 (s, 1H), 7.26e7.29 (m, 4H). 13C NMR
9. For a review of the use of CAN as a catalyst in organic synthesis, see: Sridharan,
ꢀ
V.; Menendez, J. C. Chem. Rev. 2010, 110, 3805.
(CDCl3, 62.9 MHz) d 14.3, 21.7, 22.8, 22.9, 24.2, 26.6, 31.0, 31.5, 38.3,
10. For selected examples, see: Shanmugam, P.; Perumal, P. T. Tetrahedron 2006, 62,
44.9, 105.6, 120.8, 129.6 (2C), 129.7 (2C), 130.1, 136.4, 138.1, 144.6,
194.7. Anal. Calcd for C21H27NO: C, 81.51; H, 8.79; N, 4.53. Found: C,
81.37; H, 8.54; N, 4.31.
~
ꢀ
~
9726; (b) Sridharan, V.; Avendano, C.; Menendez, J. C. Tetrahedron 2007, 63,
ꢀ
673; (c) Sridharan, V.; Perumal, P. T.; Avendano, C.; Menendez, J. C. Tetrahedron
~
ꢀ
2007, 63, 4407; (d) Sridharan, V.; Avendano, C.; Menendez, J. C. Synlett 2007,
~
ꢀ
881; (e) Sridharan, V.; Avendano, C.; Menendez, J. C. Synlett 2007, 1079;
~
ꢀ
(f) Sridharan, V.; Avendano, C.; Menendez, J. C. Synthesis 2008, 1039; (g) Srid-
haran, V.; Menendez, J. C. Org. Lett. 2008, 10, 4303; (h) Sridharan, V.; Avendano,
C.; Menendez, J. C. Tetrahedron 2009, 65, 2087; (i) Sridharan, V.; Maiti, S.;
Menendez, J. C. Chem.dEur. J. 2009, 15, 4565; (j) Sridharan, V.; Ribelles, P.;
Ramos, M. T.; Menendez, J. C. J. Org. Chem. 2009, 74, 5715; (k) Sridharan, V.;
Maiti, S.; Menendez, J. C. J. Org. Chem. 2009, 74, 9365; (l) Maiti, S.; Menendez, J.
3.4.9. 1-(n-Hexyl)-3-(2-thienyl)-6,7-dihydro-indol-4(5H)-one
ꢀ
~
ꢀ
(14b). Light brown viscous liquid. IR (neat) 2930.1, 2857.9, 1652.7,
ꢀ
1474.9, 1417.6, 1373.8, 1172.1, 762.5, 701.4 cmꢀ1 1H NMR (CDCl3,
.
ꢀ
250 MHz) d 0.81e0.95 (m, 3H),1.17e1.31 (m, 6H),1.52e1.58 (m, 2H),
ꢀ
ꢀ
C. Synlett 2009, 2249; (m) Selvam, N. P.; Perumal, P. T. Can. J. Chem. 2009, 87,
689; (n) Suryavanshi, P. A.; Sridharan, V.; Menendez, J. C. Org. Biomol. Chem.
2010, 8, 3426; (o) See also Ref. 7.
2.18e2.28 (m, 2H), 2.54 (t, J¼5.9 Hz, 2H), 2.85 (t, J¼5.8 Hz, 2H), 3.88
ꢀ
(t, J¼7.6 Hz, 2H), 6.57(s, 1H), 7.29e7.44 (m, 3H). 13C NMR (CDCl3,
62.9 MHz)
d 14.3, 22.8, 22.9, 24.2, 26.5, 30.9, 31.5, 38.3, 44.9, 105.9,
11. For examples of fused derivatives of this system, see Ref. 5 and: Magdesieva, N.
N.; Serjeeva, T. A. Zh. Org. Khim. 1985, 21, 1776.
120.8, 128.2, 128.9, 129.7, 133.1, 136.3, 144.8, 194.7. Anal. Calcd for
C18H23NOS: C, 71.72; H, 7.69; N, 4.65; S, 10.64. Found: C, 71.43; H,
7.52; N, 4.42.
12. For the synthesis of compounds 6, see: (a) Pinto, D. C. G. A.; Silva, A. M. S.; Levai,
A.; Cavaleiro, J. A. S.; Patonay, T.; Elguero, J. Eur. J. Org. Chem. 2000, 2877;
(b) Santos, M. M. C.; Silva, A. M. S.; Cavaleiro, J. A. S.; Levai, A.; Ptonay, T. Eur. J.
Org. Chem. 2007, 2877.
13. For a representative example, see: (a) Liou, J.-P.; Wu, Z.-Y.; Kuo, C.-C.; Chang, C.-
Y.; Lu, P.-Y.; Chen, C.-M.; Hsieh, H.-P.; Chang, J.-Y. J. Med. Chem. 2008, 51, 4351.
14. For representative examples, see: (a) Chilin, A.; Rodighiero, P.; Guiotto, A.
Synthesis 1998, 309; (b) Gathergood, N.; Scammells, P. J. Org. Lett. 2003, 5, 921;
(c) Shirota, O.; Hakamata, W.; Goda, Y. J. Nat. Prod. 2003, 66, 885.
15. Arai, M.; Miyauchi, Y.; Miyahara, T.; Ishikawa, T.; Saito, S. Synlett 2009, 122.
16. For representative examples, see: (a) Hsieh, M. F.; Rao, D. R.; Liao, C. C. Chem.
Commun. 1999, 1441; (b) Lamar, A. A.; Nicholas, K. M. Tetrahedron 2009, 65,
3829.
Acknowledgements
We thank MICINN (grants CTQ2009-12320-BQU and ACI2009-
0956) and UCM (Grupos de Investigacion, grant 920234) for
financial support. A three-month stay of PTP in Madrid that made
this work possible was funded by a fellowship from the Santander-
ꢀ