Toward understanding the scope of Baylis-Hillman reaction: Synthesis of 3-(2- hydroxyphenyl)indolin-2-ones and polycyclic fused furans

Article abstract of DOI:10.1016/j.tet.2010.05.087

A facile one-pot synthesis of 3-(2-hydroxyphenyl)indolin-2-ones has been developed via the TiCl₄-me- diated Baylis-Hillman (B-H) reaction of N-substituted isatins and cyclohex-2-enone, followed by treatment of the in situ generated B-H alcohols with aq HBr. Baylis-Hillman reaction of aromatic cyclic 1, 2-diones with cycloalk-2-enones under the influence of TiCl₄ has been successfully performed and the resulting Baylis-Hillman adducts have been conveniently transformed into pentacyclic and hexacyclic fused furan derivatives.

Full text of DOI:10.1016/j.tet.2010.05.087

Tetrahedron 66 (2010) 5612e5622
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Tetrahedron
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Toward understanding the scope of BayliseHillman reaction: synthesis of
3-(2- hydroxyphenyl)indolin-2-ones and polycyclic fused furans
*
Deevi Basavaiah , Suparna Roy, Utpal Das
School of Chemistry, University of Hyderabad, Central University (PO), Gachibowli, Hyderabad 500 046, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A facile one-pot synthesis of 3-(2-hydroxyphenyl)indolin-2-ones has been developed via the TiCl4-me-
diated BayliseHillman (BeH) reaction of N-substituted isatins and cyclohex-2-enone, followed by
treatment of the in situ generated BeH alcohols with aq HBr. BayliseHillman reaction of aromatic cyclic
1,2-diones with cycloalk-2-enones under the influence of TiCl4 has been successfully performed and the
resulting BayliseHillman adducts have been conveniently transformed into pentacyclic and hexacyclic
fused furan derivatives.
Received 17 February 2010
Received in revised form
23 May 2010
Accepted 24 May 2010
Available online 31 May 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
BayliseHillman reaction
3-(2-Hydroxyphenyl)indolin-2-ones
Polycyclic fused furans
Cyclic 1,2-diones
Cycloalk-2-enones
1. Introduction
3-Aryloxindole skeleton represents an interesting class of
nitrogen heterocyclic system because such kind of framework
The BayliseHillman reaction is a three component atom eco-
nomical carbonecarbon bond forming reaction involving coupling
of a-position of activated alkenes with electrophiles in the presence
possesses various biological activities like BK channel openers5
and orally active growth hormone secretagogues.6 Polycyclic
fused-furan framework is another important structural organi-
zation present in certain natural products7 and also some of
these frameworks are known to exhibit interesting biological
activities, such as inhibition of receptor tyrosine kinase,8 cyto-
toxicity,9 and anticancer activity.10 Therefore development of
facile strategies for synthesis of 3-aryloxindole derivatives11 and
polyfused furans7a,c,8,9,12 has become an attractive and chal-
lenging endeavor in synthetic chemistry. We have therefore di-
rected our efforts toward the development of convenient
methodologies for synthesis of both of these frameworks.
of a catalyst or catalytic system, providing an interesting class of
densely functionalized molecules, which are usually referred to as
the BayliseHillman adducts.1,2 During the last twenty five years
BayliseHillman reaction has grown with respect to all the three
essential components and has now become a versatile and popular
synthetic tool in organic chemistry. The BayliseHillman adducts
have become a valuable source for various organic transformations
and have been transformed into a number of carbocycles and
heterocyclic frameworks of medicinal importance.1,2 In continua-
tion of our interest in the BayliseHillman reaction3 and its appli-
cations in the synthesis of heterocyclic compounds4 we herein
report a simple and one-pot synthesis of 3-(2-hydroxyphenyl)
indolin-2-ones via the BayliseHillman reaction of N-substituted
isatins with cyclohex-2-enone followed by treatment of the in situ
formed BayliseHillman adducts with aq HBr. A facile synthesis of
pentacyclic/hexacyclic fused-furan framework from the Bay-
liseHillman adducts derived from cycloalk-2-enones and aromatic
1,2-diones is also described.
2. Results and discussion
During our earlier investigations on the development of Bay-
liseHillman reaction, we noticed a remarkable steric direction in
the TiCl4-mediated coupling of
a-keto esters with cyclohex-2-
enone derivatives.13 Thus, cyclohex-2-enone (1a) provided aldol
adducts (with syn stereochemistry) as major products (along with
the BayliseHillman adducts as the minor products) when coupled
with a-keto esters in the presence of TiCl4 while sterically more
demanding 5,5-dimethylcyclohex-2-enone (1b) gave exclusively
the BayliseHillman adducts.13 We therefore planned to examine
the coupling of isatin derivatives (cyclic a-keto amides, which are
* Corresponding author. Tel.: þ91 040 23134812; fax: þ91 40 23012460; e-mail
address: dbsc@uohyd.ernet.in (D. Basavaiah).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.05.087

D. Basavaiah et al. / Tetrahedron 66 (2010) 5612e5622
5613
O
HO
structurally similar to a-keto esters) with cyclohex-2-enone (1a)
O
O
and sterically more demanding 1b under the influence of TiCl4
with a view to understand the role of steric factors in these re-
actions. Literature survey reveals that although TiCl4 has been
systematically used for coupling of various activated alkenes with
several electrophiles, coupling of isatin derivatives with cycloalk-
2-enones has not been well studied.14
TiCl4
O
+
O
(eq 1)
CH2Cl2,
30 min, 86%
rt
N
Me
N
Me
3a
2a
1a
Accordingly, we have first examined the reaction between N-
methylisatin (2a) and 1a under the influence of TiCl4 and we were
pleased to notice the formation of only BayliseHillman adduct and
complete absence of any aldol product. The best result was
obtained when 2a (1 mmol) was treated with 1a (1 mmol) in the
presence of TiCl4 (1 mmol) in CH2Cl2 at room temperature
(25e28 ꢀC) for 30 min to provide the corresponding BayliseHill-
man (BeH) alcohol, 3-hydroxy-3-(cyclohex-2-enon-2-yl)-1-meth-
ylindolin-2-one, (3a) in 86% isolated yield (Eq. 1). Since the
product is allylic alcohol, which has the potential to undergo de-
hydration under acidic conditions leading to aromatization, it oc-
curred to us that the longer reaction time might provide the
expected phenolic derivative. Accordingly we continued the re-
action for 4 h at room temperature, but did not obtain the
expected 3-(2-hydroxyphenyl)-1-methylindolin-2-one (4a). Dur-
ing our efforts in achieving aromatization we noticed that the
treatment of 3a with aq HBr, in dichloroethane (DCE) at reflux
temperature for 6 h, provided the required aromatized compound
4a in 89% isolated yield (Eq. 2). Encouraged by this excellent result,
we felt that if these two steps can be performed in one-pot
without isolating the BeH alcohol, this strategy would lead to
a simple and practical procedure for conversion of isatin de-
rivatives into 3-(2-hydroxyphenyl)indolin-2-one derivatives via
the BayliseHillman protocol. In these efforts the best result was
obtained when 1-methylisatin (2a, 1 mmol) was treated with
cyclohex-2-enone (1a, 1 mmol) in presence of TiCl4 (1 mmol) in
dichloroethane at room temperature (25e28 ꢀC) for 30 min fol-
lowed by the treatment of the resulting reaction mixture with aq
HBr (5 mmol) at reflux temperature for 6 h, thus providing the
desired 3-(2-hydroxyphenyl)-1-methylindolin-2-one (4a) in 82%
isolated yield (Table 1, entry 1).
To understand the generality of this strategy we have subjected
representative isatin derivatives (2aek) to a similar one-pot re-
action sequence with cyclohex-2-enone to provide the corre-
sponding 3-(2-hydroxyphenyl)indolin-2-one derivatives (4aek) in
51e85% isolated yields (Table 1). Structures of the compounds 4b,
4e (Fig. 1), and 4g (Fig. 2) were also confirmed by single crystal
X-ray data analysis.15
Figure 1. ORTEP diagrams of 4b and 4e (Hydrogen atoms are omitted for clarity).
Table 1
Synthesis of 3-(2-hydroxyphenyl)indolin-2-ones (4aek) via the reaction of isatin
derivatives (2aek) with cyclohex-2-enone (1a)a
4g
20
Figure 2. ORTEP diagrams of 4g and 20 (Hydrogen atoms are omitted for clarity).
Entry
R1
R2
Isatin
Productb
Yieldc (%)
O
1
2
3
4
5
6
7
8
Me
Me
Et
Et
CH2Ph
CH2Ph
CH2Ph
CH2Ph
Ph
H
Cl
H
Cl
H
Cl
Br
Me
H
2a
2b
2c
2d
2e
2f
2g
2h
2i
4a
4bd
4c
82
76
83
59
65
77
63
85
55
51
54
HO
aq.HBr
OH
(eq 2)
O
DCE
reflux, 6 h
89%
O
N
4d
4ed
4f
N
Me
Me
4a
3a
4gd
4h
4i
9
10
11
Ph
Ph
Cl
Me
2j
2k
4j
4k
We have then examined the reaction of isatin derivative (2a) with
5,5-dimethylcyclohex-2-enone (1b), in the presence of TiCl4, which
as expected provided the BayliseHillman adduct (5) in 91% isolated
yield. Similar reaction of cyclopent-2-enone (1c) with 2a also gave
the expected BeH alcohol 6 in 53% isolated yield (Scheme 1).
Next we have turned our attention toward the TiCl4-mediated
BayliseHillman reaction between cyclic aromatic 1,2-diones as
electrophiles and cycloalk-2-enones as activated alkenes. We have
a
All the reactions were carried out on 1 mmol scale of isatins (2aek) with
cyclohex-2-enone (1a, 1 mmol) in the presence of TiCl4 (1 mmol) at room temper-
ature (25e28 ꢀC) followed by the treatment with aq HBr (5 mmol) in dichloroethane
at reflux temperature.
b
All the compounds were isolated as solids and fully characterized.
Isolated yields based on isatins (2aek).
Structures of the compounds 4b, 4e, and 4g were further confirmed by single
c
d
crystal X-ray data analysis.15

5614
D. Basavaiah et al. / Tetrahedron 66 (2010) 5612e5622
O
O
Table 2 (continued )
HO
HO
O
Entry
Dione
Cycloalk-2-enone
T (h)
Productb yield (%)c
1b
1c
O
O
O
O
TiCl4
TiCl4
OH
N
Me
N
Me
N
Me
DCE, rt
DCE, rt
8d
7c
1b
48
6
5
2a
2 h,
53%
7 h, 91%
O
15 (67%)
Scheme 1. Synthesis of BayliseHillman alcohols (5, 6) from 1-methylisatin (2a) and
cyclic enones (1b, c) in the presence of TiCl4.
O
OH
carried out reaction between 1,2-acenaphthenequinone (7a,
1 mmol) and cyclohex-2-enone (1a, 1 mmol) in presence of TiCl4
(1 mmol) in dichloromethane at room temperature (25e28 ꢀC) for
30 min which afforded the expected BayliseHillman adduct, 2-
hydroxy-2-(cyclohex-2-enon-2-yl)-2H-acenaphthylen-1-one (8) in
87% isolated yield (Table 2, entry 1). In order to extend the scope of
this reactionwe have used representative activated alkenes 1aec for
coupling with electrophiles, 7a, [9,10]-phenanthrenedione (7b),
pyrene-[4,5]-dione (7c), and 1,2-aceanthrenequinone (7d) under
the influence of TiCl4 to provide the corresponding BeH alcohols
9e19 in 53e90% isolated yields (Table 2, entries 2e12). It is worth
mentioning here our earlier research work on the TiCl4-mediated
9e
7c
7d
7d
1c
1a
1b
6
6
O
16
(53%)
O
OH
O
10
11
(90%)
17
O
OH
O
24
18 (85%)
Table 2
Synthesis of BayliseHillman alcohols (8e19) from the aromatic cyclic 1,2-diones
a
(7aed) and cyclic enones (1aec) in the presence of TiCl4
O
OH
O
12
7d
1c
10
Entry
1
Dione
Cycloalk-2-enone
T (h)
Productb yield (%)c
19 (70%)
O
OH
O
a
All the reactions were carried out on a 1 mmol scale of aromatic 1,2-diones (7aed)
with cyclic enones [1a, b (1 mmol) and for 1c 1.5 mmol] in the presence of TiCl4
(1 mmol) at room temperature (25e28 ꢀC) in CH2Cl2 (for 15 and 18 DCE was used).
7a
1a
0.5
b
All compounds were isolated as solids and fully characterized.
Isolated yields based on the aromatic 1,2-diones (7aed).
c
8 (87%)
Compound 15 was isolated along with side product (30%) (as shown by 1H NMR).
Minor side product (presumably aldol product) (16a) was also isolated in 19%
d
e
O
OH
O
yield along with compound 16.
2
3
4
7a
7a
7b
1b
1c
1a
1
BayliseHillman reaction between cyclic aromatic 1,2-diones and
alkyl vinyl ketones, which provided fused furanecarboxaldehydes.16
With a view to obtain the phenolic derivative (aromatized com-
pound), in one-pot, we have carried out reaction between 1,2-ace-
naphthenequinone (7a,1 mmol), and cyclohex-2-enone (1a,1 mmol)
in presence of TiCl4 (1 mmol) in dichloroethane at room temperature
for 30 min followed by the treatment of in situ formed BH-alcohol
with aq HBr (5 mmol) at reflux temperature for 6 h as in the case of N-
substituted isatins. The expected phenolic compound, i.e., 2-(2-
hydroxyphenyl)-2H-acenaphthylen-1-one (20) was obtained in 73%
isolated yield (Scheme 2). Structure of compound 20 was further
confirmed by single crystal X-ray data analysis (Fig. 2).15
9 (78%)
O
OH
O
5
10 (72%)
O
OH
0.5
O
11(70%)
O
HO
OH
O
O
O
O
O
OH
5
6
7b
7b
1b
1c
0.5
O
aq.HBr
TiCl
DCE
rt, 30 min.
+
O
reflux, 6 h
73%
12 (79%)
7a
1a
20
O
OH
Scheme 2. Synthesis of 2-(2-hydroxyphenyl)-2H-acenaphthylen-1-one (20) from 1,2-
acenaphthenequinone (7a) and cyclohex-2-enone (1a).
1
O
13 (72%)
To understand the generality of this strategy we have selected
three aromatic 1,2-diones 7bed as electrophiles for coupling with
cyclohex-2-enoneinthe presence of TiCl4 followedbytreatment with
aq HBr. Unfortunately these electrophiles, 7bed, did not provide the
expected phenolic derivatives as these reactions were not clean. At
this stage, wefeltthatstep-wisestrategymightofferbetterresult. Our
O
OH
7
7c
1a
12
O
14 (61%)

D. Basavaiah et al. / Tetrahedron 66 (2010) 5612e5622
5615
attempts to convert alcohols 11, 14, and 17 into the corresponding
aromatized compounds by treatment with aq HBr were not suc-
cessful. During thesestudies we foundthatthe treatmentof theallylic
alcohol 11 with methanesulfonic acid led to the formation of fused
furan derivative (21) instead of the phenolic derivative. Thus the
treatment of the alcohol (11, 1 mmol) with methanesulfonic acid
(1 mmol) in dichloroethane at reflux temperature for 30 min pro-
vided the furan derivative 21 in 86% isolated yield (Table 3, entry 1). In
order to understand the generality of this methodology we have
transformed the BayliseHillman alcohols 12e16 into the fused furan
derivatives 22e26 in 20e96% isolated yields via the treatment with
methanesulfonic acid (Table 3). Structures of the compounds 21 and
23 were also confirmed by single crystal X-ray data analysis (Fig. 3).15
A plausible mechanism for the transformation of the BeH alcohols
21
23
Figure 3. ORTEP diagrams of 21 and 23 (Hydrogen atoms are omitted for clarity).
into fused-furan framework is given in Scheme 3. However the
BayliseHillman alcohol 17 failed to provide the corresponding fused
furan derivative as this reaction was not clean.
Table 3
Synthesis of furan derivatives (21e26) from the BayliseHillman alcohols (11e16) via
treatment with methanesulfonic acida
O
O
O
O
O
OH
O
R3
R3
OH
OH
H
R3
MeSO3H
DCE
O
H
n
O
O
O
n
O
R3
O
21
11
Scheme 3. Plausible mechanism for synthesis of furan derivatives.
reflux,
0.5-1 h
20-96%
21-26
11-16
R3 = H, Me
n = 0, 1
However, similar treatment of the BayliseHillman alcohol 8 with
methanesulfonic acid did not provide the expected furan derivative.
Instead, interesting spiro-fused compound 27 was obtained in 65%
isolated yield (Eq. 3) when methanesulfonic acid (3 equiv) was used
(1 equiv of methanesulfonic acid gave inferior yield). Structure of 27
and its (ꢁ)-cis-cis-cis-stereo-chemistry17 were determined by the
single crystal X-ray data analysis (Fig. 4).15,18e20 Also the BeH alcohol
Entry
1
B H alcohol
Productb
T (min)
Yieldc (%)
86
O
O
OH
30
O
11
O
d
21
O
O
9 gave fused furan framework 28 under similar conditions.20,21
A
OH
plausible mechanism is presented in Scheme 4. The furan in-
termediate A, formed in situ, might react with BeH alcohol (Frie-
deleCrafts reaction) giving risetothekeyintermediate(oxonium ion)
B, which mightthen undergo ene-type cyclization in a stereoselective
manner at C-3 and C-21 with cis orientation because of the presence
of acenaphthene rings. The single crystal X-ray structure of the
compound 27 clearly shows that the reaction pathway also controls
stereochemistry at spiro carbon (C-10/20) leading to the formation of
racemic 27 with cis-cis-cis stereochemistry.
2
30
30
30
60
89
96
O
O
22
12
O
O
OH
3
O
O
13
23d
O
O
OH
4
50
O
O
8'
9'
R
6'
24
1
7'
24
14
25
23
O
10'
11'
O
R
5'
12'
O
O
22
OH
OH
26
10
O
R
R
4'
3'
2'
5e
43f
1'
20
11
21
MeSO3H
12
O
(eq. 3)
O
25
13O 2
9
O
19
DCE
O
15
3
8
18
17
14
15
reflux, 1 h
4
7
5
16
O
6
O
8 (R = H)
9 (R = Me)
OH
(+)-27 (R = H); 65%
(+)-28 (R = Me); 58%
R
R
6
60
20
O
O
16
26
a
All the reactions were carried out on a 1 mmol scale of BayliseHillman alcohols
(11e16) in the presence of methanesulfonic acid (1 mmol) in dichloroethane at
reflux temperature.
3. Conclusion
b
All the compounds were isolated as solids and fully characterized.
Isolated yields based on the BayliseHillman alcohols (11e16).
c
d
In conclusion, we have developed a facile one-pot protocol
for transformation of N-substituted isatins into 3-(2-hydroxy-
phenyl)indolin-2-one derivatives via the TiCl4-mediated Bay-
liseHillman reaction with cyclohex-2-enone followed by
treatment of the in situ generated BeH alcohols with aq HBr. A
Structures of compounds 21 and 23 were further confirmed by single crystal
Xeray data analysis.15
e
BayliseHillman adduct 15 was used as such along with the minor side product
as substrate for treatment with methanesulfonic acid.
f
Yield was calculated based on the amount of BayliseHillman alcohol present in
the mixture.

5616
D. Basavaiah et al. / Tetrahedron 66 (2010) 5612e5622
4. Experimental section
4.1. General remarks
Melting points were recorded on a Superfit (India) capillary
melting point apparatus and are uncorrected. IR spectra were
recorded on a JASCO-FTIR model 5300 spectrometer using solid
samples as KBr plates. For all the compounds 1H NMR (400 MHz)
and 13C NMR (100 MHz) spectra were recorded in deutero-
chloroform (CDCl3) on a Bruker-AVANCE-400 spectrometer using
tetramethylsilane (TMS,
d
¼0) as an internal standard or in DMSO-
d6 at room temperature. Elemental analyses were recorded on
a Thermo-Finnigan Flash EA 1112 analyzer. Mass spectra were
recorded on Shimadzu-LCMS-2010 A mass spectrometer. The
X-ray diffraction measurements were carried out at 298 K on
a Bruker SMART APEX CCD area detector system equipped with
a graphite monochromator and a Mo-K
a fine-focus sealed tube
ꢀ
(l¼0.71073 A).
4.2. Representative procedure
4.2.1. Synthesis of 3-hydroxy-3-(cyclohex-2-enon-2-yl)-1-methyl-
indolin-2-one (3a). To a stirred solution of 1-methylisatin (2a)
(1 mmol, 0.161 g) and cyclohex-2-enone (1a, 1 mmol, 0.096 g,
0.096 mL) in CH2Cl2 (1 mL) TiCl4 (1 mmol, 0.5 mL of 2 M solution in
CH2Cl2) was added at 0 ꢀC. The reaction mixture was stirred for
30 min at room temperature (25e28 ꢀC). Water (2 mL) was then
added to the reaction mixture and extracted with CH2Cl2 (3ꢂ5 mL).
Combined organic layer was dried over anhydrous Na2SO4. Solvent
was evaporated and the residue, thus obtained, was subjected to
column chromatography (silica gel, 60% ethyl acetate in hexanes) to
afford the desired product (3a) as yellow solid in 86% (0.220 g)
isolated yield. Rf (50% EtOAc in hexanes) 0.25; mp: 159e161 ꢀC; IR
Figure 4. ORTEP diagram of 27 (Hydrogen atoms and one dichloromethane molecule
are omitted for clarity).
(KBr):
1.85e2.06 (m, 2H), 2.27e2.43 (m, 2H), 2.44e2.52 (m, 2H), 3.22 (s,
n ;
3375, 1703, 1672, 1612 cmꢃ1 1H NMR (400 MHz):
simple two-step methodology for synthesis of fused-furan
framework has also been developed via the treatment of the
BayliseHillman adducts, obtained by TiCl4-mediated Bay-
liseHillman reaction between cyclic aromatic 1,2-diones and
cyclic enones, with methanesulfonic acid.
d
3H), 4.08 (br s, 1H), 6.83 (d, 1H, J¼7.6 Hz), 6.96e7.04 (m, 1H), 7.13 (d,
1H, J¼7.2 Hz), 7.27e7.34 (m, 1H), 7.36e7.43 (m, 1H); 13C NMR
(100 MHz):
d 22.39, 25.83, 26.41, 38.37, 76.00, 108.58, 122.81,
123.58, 129.92, 130.09, 138.30, 144.37, 147.74, 176.63, 198.29; LCMS
H
O
O
HO
O
O
O
O
H2O
O
O
Np
H
8
H
Np
O
Np
H
O
O
Np
Np
O
OH2
O
F-C
reaction
O
OH2
O
O
O
O
A
B
ene-type
cyclization
F-C = Friedel-Crafts
H
O
O
Np
O
O
21
1'
20
O
O
O
3
O
Np
27
(+)-cis-cis-cis17
stereoselection
at C-3,C-20 and C-21
Scheme 4. Plausible mechanism for synthesis of spiro derivative 27.

D. Basavaiah et al. / Tetrahedron 66 (2010) 5612e5622
5617
(m/z): 258 (MþH)þ; Analysis calcd for C15H15NO3: C, 70.02; H, 5.88;
4.2.5. 1-Ethyl-3-(2-hydroxyphenyl)indolin-2-one (4c). Yield: 83%; Rf
(20% EtOAc in hexanes) 0.35; light yellow solid; mp: 126e128 ꢀC; IR
(KBr):
N, 5.44. Found: C, 70.15; H, 5.82; N, 5.55.
n ; d 1.28 (t, 3H,
3271, 1682 cmꢃ1 1H NMR (400 MHz):
4.2.2. 3-(2-Hydroxyphenyl)-1-methylindolin-2-one (4a). To a stir-
red solution of 3-hydroxy-3-(cyclohex-2-enon-2-yl)-1-methyl-
indolin-2-one (3a) (1 mmol, 0.257 g) in dichloroethane (1 mL) aq
HBr (48%, 5 mmol, 0.405 g, 0.271 mL) was added at room temper-
ature (25e28 ꢀC) and the reaction mixture was heated under reflux
for 6 h. The reaction mixture was allowed to cool to room tem-
perature and diluted with water (5 mL). Organic layer was sepa-
rated and aqueous layer was extracted with CH2Cl2 (3ꢂ5 mL).
Combined organic layer was dried over anhydrous Na2SO4. Solvent
was evaporated and the crude product, thus obtained, was purified
through column chromatography (silica gel, 30% ethyl acetate in
hexanes) to afford the desired product (4a) as yellow solid in 89%
(0.212 g) isolated yield. Rf (20% EtOAc in hexanes) 0.28; mp:
J¼7.2 Hz), 3.78 (q, 2H, J¼7.2 Hz), 5.09 (s, 1H), 6.78e6.86 (m, 1H),
6.90 (d, 1H, J¼7.2 Hz), 6.98 (d, 1H, J¼8.0 Hz), 7.01e7.08 (m, 1H),*
7.13e7.23 (m, 2H), 7.31e7.44 (m, 2H), 9.20 (br s, 1H); 13C NMR
(100 MHz):
d 12.64, 35.26, 48.01, 109.22, 118.98, 120.74, 123.08,
123.31, 126.35,126.56, 127.32,128.68,129.25,143.67, 156.26,178.24;
LCMS (m/z): 254 (MþH)þ. Analysis calcd for C16H15NO2: C, 75.87; H,
5.97; N, 5.53. Found: C, 75.92; H, 6.12; N, 5.50. (*It is unresolved dd).
4.2.6. 5-Chloro-1-ethyl-3-(2-hydroxyphenyl)indolin-2-one
Yield: 59%; Rf (20% EtOAc in hexanes) 0.22; light yellow solid; mp:
187e189 ꢀC; IR (KBr): 3232,1674 cmꢃ1; 1H NMR (400 MHz):
1.27
(4d).
n
d
(t, 3H, J¼7.6 Hz), 3.71e3.84 (m, 2H), 5.05 (s, 1H), 6.78e6.91 (m, 3H),
6.95 (d, 1H, J¼8.0 Hz), 7.11e7.19 (m, 1H), 7.28 (s, 1H), 7.34 (dd, 1H,
150e152 ꢀC; IR (KBr):
n ;
3180, 1680 cmꢃ1 1H NMR (400 MHz):
J¼8.4, 1.6 Hz), 8.68 (s, 1H); 13C NMR (100 MHz):
d 12.54, 35.40,
d
3.24 (s, 3H), 5.11 (s, 1H), 6.77e6.86 (m, 1H), 6.89 (d, 1H, J¼7.2 Hz),
47.98, 109.92, 118.64, 120.89, 122.76, 126.41, 127.54, 128.53, 128.57,
128.91, 129.46, 142.17, 155.82, 177.70; LCMS (m/z): 288 (MþH)þ, 290
(Mþ2þH)þ. Analysis calcd for C16H14ClNO2: C, 66.79; H, 4.90; N,
4.87. Found: C, 66.65; H, 4.88; N, 4.77.
6.96 (d, 1H, J¼8.0 Hz), 7.05 (d, 1H, J¼8.0 Hz), 7.15e7.24 (m, 2H), 7.34
(d, 1H, J¼7.2 Hz), 7.38e7.47 (m, 1H), 9.20 (s, 1H); 13C NMR
(100 MHz):
d 26.62, 47.92, 109.08, 118.96, 120.75, 123.23, 123.29,
126.13, 126.32, 127.32, 128.74, 129.27, 144.56, 156.20, 178.58; LCMS
(m/z): 240 (MþH)þ. Analysis calcd for C15H13NO2: C, 75.30; H, 5.48;
N, 5.85. Found: C, 75.46; H, 5.50; N, 5.91.
4.2.7. 1-Benzyl-3-(2-hydroxyphenyl)indolin-2-one (4e). Yield: 65%;
Rf (20% EtOAc in hexanes) 0.38; light yellow solid; mp: 147e148 ꢀC;
IR (KBr):
n ; d 4.90 and 4.95
3279, 1682 cmꢃ1 1H NMR (400 MHz):
4.2.3. Representative procedure: one-pot synthesis of 3-(2-hydroxy-
phenyl)-1-methylindolin-2-one (4a). To a stirred solution of 1-
methylisatin (2a) (1 mmol, 0.161 g) and cyclohex-2-enone (1a,
1 mmol, 0.096 g, 0.096 mL) in dichloroethane (2 mL) TiCl4 (1 mmol,
0.5 mL of 2 M solution in CH2Cl2) was added at 0 ꢀC. The reaction
mixture was stirred for 30 min at room temperature (25e28 ꢀC).
HBr (aq) (48%, 5 mmol, 0.405 g, 0.271 mL) was added to the re-
action mixture at room temperature and heated under reflux for
6 h. The reaction mixture was allowed to cool to room temperature
and diluted with water (5 mL). Organic layer was separated and
aqueous layer was extracted with CH2Cl2 (3ꢂ5 mL). Combined or-
ganic layer was dried over anhydrous Na2SO4. Solvent was evapo-
rated and the crude product, thus obtained, was purified through
column chromatography (silica gel, 30% ethyl acetate in hexanes) to
afford the desired product (4a) as yellow solid in 82% (0.195 g)
isolated yield. Spectral data (IR, 1H NMR, 13C NMR and LCMS) and
melting point are in complete agreement with that of 4a prepared
in two step procedure.
(ABq, 2H, J¼15.6 Hz), 5.18 (s, 1H), 6.78e6.87 (m, 2H), 6.91 (d, 1H,
J¼7.2 Hz), 7.01 (d, 1H, J¼8.0 Hz), 7.08e7.21 (m, 2H), 7.22e7.34 (m,
7H), 8.96 (br s, 1H); 13C NMR (100 MHz):
d 44.20, 47.93, 110.03,
118.82, 120.84, 123.27, 123.35, 126.08, 126.63, 127.35, 127.55, 127.88,
128.59, 128.93, 129.31, 135.24, 143.70, 156.10, 178.70; LCMS (m/z):
316 (MþH)þ. Analysis calcd for C21H17NO2: C, 79.98; H, 5.43; N,
4.44. Found: C, 79.85; H, 5.47; N, 4.40.
4.2.7.1. Crystal data for 4e. Empirical formula, C21H17NO2; for-
mula weight, 315.36; crystal color, habit: colorless, plate; crystal
dimensions, 0.22ꢂ0.13ꢂ0.09 mm3; crystal system, triclinic; lattice
ꢀ
ꢀ
type, primitive; lattice parameters, a¼11.102 (8) A, b¼12.101 (8) A,
ꢀ
c¼12.537 (9) A;
a
¼89.327(13);
b
¼78.942 (13);
g
¼84.167 (13);
V¼1644.5 (19) A ; space group, Pꢃ1; Z¼4; Dcalcd¼1.261 g/cm3;
3
ꢀ
F000¼664;
l
(Mo Ka)¼0.71073 A; R (Iꢄ2s1)¼0.0664, wR2¼0.1807.
ꢀ
Detailed X-ray crystallographic data is available from the Cam-
bridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2
1EZ, UK (for compound 4e CCDC # 753489).
4.2.4. 5-Chloro-3-(2-hydroxyphenyl)-1-methylindolin-2-one
Yield: 76%; Rf (20% EtOAc in hexanes) 0.20; light yellow solid; mp:
186e188 ꢀC; IR (KBr): 3163,1680 cmꢃ1; 1H NMR (400 MHz):
3.24
(4b).
4.2.8. 1-Benzyl-5-chloro-3-(2-hydroxyphenyl)indolin-2-one
Yield: 77%; Rf (20% EtOAc in hexanes) 0.33; light yellow solid; mp:
158e161 ꢀC; IR (KBr): 3190, 1693 cmꢃ1 1H NMR (400 MHz):
(4f).
n
d
n
;
(s, 3H), 5.07 (s, 1H), 6.80e6.93 (m, 3H), 6.95 (d, 1H, J¼8.0 Hz),
d
4.89 and 4.95 (ABq, 2H, J¼15.6 Hz), 5.14 (s, 1H), 6.72 (d, 1H,
7.12e7.22 (m, 1H), 7.28 (s, 1H), 7.36 (dd, 1H, J¼8.4, 1.6 Hz), 8.67 (s,
J¼8.0 Hz), 6.81e6.98 (m, 3H), 7.12e7.37 (m, 8H), 8.46 (s, 1H); 13C
1H); 13C NMR (100 MHz):
d 26.77, 47.92, 109.84, 118.73, 120.94,
NMR (100 MHz):
d 44.30, 47.94, 110.81, 118.45, 120.98, 122.73,
122.68, 126.26,127.51,128.52,128.66,128.75,129.50,143.09,155.78,
178.03; LCMS (m/z): 274 (MþH)þ, 276 (Mþ2þH)þ. Analysis calcd
for C15H12ClNO2: C, 65.82; H, 4.42; N, 5.12. Found: C, 65.68; H, 4.45;
N, 5.16.
126.13, 127.30, 127.85, 128.02, 128.49, 128.75, 128.92, 129.01, 129.54,
134.89, 142.12, 155.62, 178.11; LCMS (m/z): 350 (MþH)þ, 352
(Mþ2þH)þ. Analysis calcd for C21H16ClNO2: C, 72.10; H, 4.61; N,
4.00. Found: C, 72.18; H, 4.55; N, 4.12.
4.2.4.1. Crystal data for 4b. Empirical formula, C15H12ClNO2;
formula weight, 273.71; crystal color, habit: colorless, plate; crystal
dimensions, 0.30ꢂ0.20ꢂ0.12 mm3; crystal system, triclinic; lattice
4.2.9. 1-Benzyl-5-bromo-3-(2-hydroxyphenyl)indolin-2-one
Yield: 63%; Rf (20% EtOAc in hexanes) 0.31; light yellow solid; mp:
179e180 ꢀC; IR (KBr): 3188,1687 cmꢃ1; 1H NMR (400 MHz):
4.89
and 4.95 (ABq, 2H, J¼16.0 Hz), 5.15 (s, 1H), 6.68 (d, 1H, J¼8.4 Hz),
6.81e6.89 (m, 1H), 6.91 (d, 1H, J¼6.4 Hz), 6.96 (d, 1H, J¼8.0 Hz),
7.12e7.21 (m, 1H), 7.22e7.43 (m, 7H), 8.41 (s, 1H); 13C NMR
(4g).
ꢀ
ꢀ
n
d
type, primitive; lattice parameters, a¼10.132 (3) A, b¼10.298 (3) A,
ꢀ
c¼14.543 (4) A;
a
¼101.957 (5);
b
¼95.847 (5);
g
¼114.244 (5);
V¼1323.5 (7) A ; space group, Pꢃ1; Z¼4; Dcalcd¼1.374 g/cm3;
3
ꢀ
ꢀ
F000¼568;
l
(Mo Ka)¼0.71073 A; R (Iꢄ2s1)¼0.0436, wR2¼0.1117.
(100 MHz):
d 44.28, 47.90, 111.28, 116.04, 118.44, 121.02, 122.75,
Detailed X-ray crystallographic data is available from the Cam-
bridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2
1EZ, UK (for compound 4b CCDC # 753488).
127.30, 127.89, 128.02, 128.85, 129.01, 129.31, 129.54, 131.39, 134.88,
142.64, 155.59, 177.95; LCMS (m/z): 394 (MþH)þ, 396 (Mþ2þH)þ.

5618
D. Basavaiah et al. / Tetrahedron 66 (2010) 5612e5622
Analysis calcd for C21H16BrNO2: C, 63.97; H, 4.09; N, 3.55. Found: C,
63.85; H, 4.13; N, 3.62.
7.12 (d, 1H, J¼6.8 Hz), 7.24e7.34 (m, 2H); 13C NMR (100 MHz):
d
26.41, 27.90, 28.36, 34.03, 39.87, 51.92, 75.92, 108.64, 122.84,
123.46, 129.94, 130.06, 137.41, 144.42, 145.41, 176.57, 198.35; LCMS
(m/z): 286 (MþH)þ. Analysis calcd for C17H19NO3: C, 71.56; H, 6.71;
N, 4.91. Found: C, 71.35; H, 6.78; N, 4.98.
4.2.9.1. Crystal data for 4g. Empirical formula, C21H16BrNO2; for-
mula weight, 394.26; crystal color, habit: colorless, plate; crystal
dimensions, 0.40ꢂ0.15ꢂ0.05 mm3; crystal system, triclinic; lattice
ꢀ
ꢀ
type, primitive; lattice parameters, a¼8.024 (3) A, b¼10.882 (4) A,
4.2.15. 3-Hydroxy-3-(cyclopent-2-enon-2-yl)-1-methylindolin-2-one
ꢀ
c¼11.554 (4) A;
a
¼101.870 (7);
b
¼105.925 (7);
g
¼102.388 (7);
(6). Yield: 53%; Rf (50% EtOAc in hexanes) 0.15; reaction time: 2 h,
V¼909.2 (6) A ; space group, Pꢃ1; Z¼2; Dcalcd¼1.438 g/cm3;
gray solid; mp: 136e138 ꢀC; IR (KBr): 3350, 1697,1687, 1610 cmꢃ1
n ;
3
ꢀ
ꢀ
F000¼400;
l
(Mo Ka)¼0.71073 A; R (Iꢄ2s1)¼0.0658, wR2¼0.1404.
1H NMR (400 MHz):
d 2.42e2.49 (m, 2H), 2.59e2.67 (m, 2H), 3.22
Detailed X-ray crystallographic data is available from the Cam-
bridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2
1EZ, UK (for compound 4g CCDC # 753,490).
(s, 3H), 4.57 (br, 1H), 6.86 (d, 1H, J¼7.6 Hz), 7.02e7.12 (m, 1H),
7.30e7.38 (m, 2H), 7.52 (t, 1H, J¼2.8 Hz); 13C NMR (100 MHz):
d
26.47, 26.75, 35.36, 75.20, 108.71, 123.31, 124.54, 129.04, 130.32,
143.87, 144.11, 160.42, 175.42, 208.19; LCMS (m/z): 244 (MþH)þ.
Analysis calcd for C14H13NO3: C, 69.12; H, 5.39; N, 5.76. Found: C,
69.21; H, 5.33; N, 5.72.
4.2.10. 1-Benzyl-3-(2-hydroxyphenyl)-5-methylindolin-2-one (4h).
Yield: 85%; Rf (20% EtOAc in hexanes) 0.38; orange solid; mp:
101e103 ꢀC; IR (KBr): 3273,1682 cmꢃ1; 1H NMR (400 MHz):
n d 2.34
(s, 3H), 4.88 and 4.92 (ABq, 2H, J¼16.0 Hz)#, 5.16 (s, 1H), 6.72 (d, 1H,
J¼8.0 Hz), 6.79e6.88 (m, 1H), 6.93 (d, 1H, J¼7.2 Hz), 7.00e7.10 (m,
4.2.16. 2-Hydroxy-2-(cyclohex-2-enon-2-yl)-2H-acenaphthylen-1-
one (8). Yield: 87%; Rf (50% EtOAc in hexanes) 0.50; reaction time:
2H), 7.11e7.38 (m, 7H), 9.00 (br, 1H); 13C NMR (100 MHz):
d
21.23,
30 min yellow solid; mp: 177e178 ꢀC; IR (KBr):
n
3427, 1712, 1666,
44.20, 48.00, 109.81, 118.92, 120.82, 123.48, 126.47, 126.90, 127.32,
127.50, 127.85, 128.91, 129.28, 132.97, 135.30, 141.30, 156.17, 178.64;
LCMS (m/z): 330 (MþH)þ. Analysis calcd for C22H19NO2: C, 80.22; H,
5.81; N, 4.25. Found: C, 80.35; H, 5.76; N, 4.36. # long peaks of both
1604 cmꢃ1; 1H NMR (400 MHz):
d 1.87e2.05 (m, 2H), 2.23e2.39 (m,
2H), 2.40e2.50 (m, 2H), 3.92 (br s, 1H), 7.36 (t,1H, J¼4.4 Hz), 7.42 (d,
1H, J¼6.8 Hz), 7.56e7.62 (m, 1H), 7.70e7.78 (m, 1H), 7.86 (d, 1H,
J¼8.0 Hz), 7.99 (d, 1H, J¼6.8 Hz), 8.09 (d, 1H, J¼8.0 Hz); 13C NMR
the parts of ABq merge and appear as a single peak at
d
4.90.
(100 MHz): d 22.39, 25.87, 38.21, 79.88, 120.30, 122.30, 125.76,
128.40, 128.47, 130.81, 131.45, 131.72, 139.39, 139.75, 141.58, 147.99,
198.65, 202.61; LCMS (m/z): 279 (MþH)þ. Analysis calcd for
C18H14O3: C, 77.68; H, 5.07. Found: C, 77.56; H, 5.12.
4.2.11. 3-(2-Hydroxyphenyl)-1-phenylindolin-2-one (4i). Yield: 55%;
Rf (20% EtOAc in hexanes) 0.33; light yellow solid; mp: 125e127 ꢀC; IR
(KBr):
n ; d 5.27 (s, 1H),
3304, 1693 cmꢃ1 1H NMR (400 MHz):
6.83e6.95 (m, 2H), 6.99e7.09 (m, 2H), 7.17e7.27 (m, 2H), 7.28e7.35
4.2.17. 2-Hydroxy-2-(5,5-dimethylcyclohex-2-enon-2-yl)-2H-ace-
(m, 1H), 7.36e7.47 (m, 4H), 7.49e7.58 (m, 2H), 8.78 (br, 1H); 13C NMR
naphthylen-1-one (9). Yield: 78%; Rf (50% EtOAc in hexanes) 0.66; re-
(100 MHz):
d
48.28, 110.38, 119.11, 120.98, 123.41, 123.69, 126.19,
action time: 1 h, gray solid; mp: 176e177 ꢀC; IR (KBr):
n
3325, 1709,
126.38, 126.50, 126.63, 127.65, 128.67, 129.45, 129.82, 133.86, 144.76,
156.11, 178.10; LCMS (m/z): 302 (MþH)þ. Analysis calcd for
C20H15NO2: C, 79.72; H, 5.02; N, 4.65. Found: C, 79.56; H, 5.08; N, 4.61.
1666, 1602 cmꢃ1; 1H NMR (400 MHz):
d 0.98 (s, 3H), 1.02 (s, 3H), 2.16,
and 2.21 (ABq, 2H, J¼16.0 Hz), 2.35 (d, 2H, J¼4.4 Hz), 3.84 (s, 1H),
7.19e7.31 (m, 1H), 7.42 (d, 1H, J¼6.8 Hz), 7.53e7.65 (m, 1H), 7.70e7.78
(m, 1H), 7.86 (d, 1H, J¼8.4 Hz), 7.99 (d, 1H, J¼7.2 Hz), 8.09 (d, 1H,
4.2.12. 5-Chloro-3-(2-hydroxyphenyl)-1-phenylindolin-2-one (4j).
Yield: 51%; Rf (20% EtOAc in hexanes) 0.30; light yellow solid; mp:
J¼8.0 Hz); 13C NMR (100 MHz):
d 28.12, 28.18, 34.05, 39.96, 51.81, 79.83,
120.20, 122.34, 125.81, 128.42, 128.50, 130.89, 131.48, 131.77, 138.52,
139.75, 141.67, 145.65, 198.78, 202.59; LCMS (m/z): 305 (MꢃH)þ. Anal-
ysis calcd for C20H18O3: C, 78.41; H, 5.92. Found: C, 78.49; H, 5.84.
128e130 ꢀC; IR (KBr): 3339,1701 cmꢃ1; 1H NMR (400 MHz):
n d 5.19
(s, 1H), 6.80 (d, 1H, J¼8.4 Hz), 6.84e6.95 (m, 2H), 7.00 (d, 1H,
J¼7.2 Hz), 7.12e7.20 (m, 1H), 7.22e7.27 (m, 1H), 7.28 (s, 1H),
7.34e7.47 (m, 3H), 7.48e7.58 (m, 2H), 8.18 (s, 1H); 13C NMR
4.2.18. 2-Hydroxy-2-(cyclopent-2-enon-2-yl)-2H-acenaphthylen-1-
(100 MHz):
d
48.24, 111.02, 118.38, 120.98, 122.82, 126.17, 126.55,
one (10). Yield: 72%; Rf (50% EtOAc in hexanes) 0.43; reaction time: 5 h,
128.15, 128.46, 128.77, 128.84, 129.00, 129.58, 129.90, 133.78, 143.14,
155.50, 177.45; LCMS (m/z): 334 (M-2þH)þ, 336 (MþH)þ, 338
(Mþ2þH)þ. Analysis calcd for C20H14ClNO2: C, 71.54; H, 4.20; N,
4.17. Found: C, 71.65; H, 4.25; N, 4.07.
gray solid; mp: 152e154 ꢀC; IR (KBr): 3427, 1728, 1674, 1610 cmꢃ1; 1H
n
NMR (400 MHz): d2.40e2.52 (m, 2H), 2.53e2.66(m, 2H), 4.95 (br s,1H),
7.30e7.41 (m, 1H),* 7.57e7.70 (m, 2H), 7.71e7.80 (m, 1H), 7.91(d, 1H,
J¼8.0 Hz), 7.99 (d, 1H, J¼7.2 Hz), 8.13 (d, 1H, J¼8.4 Hz); 13C NMR
(100 MHz): d 26.84, 35.29, 79.19, 121.24, 122.74, 125.93, 128.59, 128.88,
4.2.13. 3-(2-Hydroxyphenyl)-5-methyl-1-phenylindolin-2-one (4k).
Yield: 54%; Rf (20% EtOAc in hexanes) 0.35; light yellow solid; mp:
130.64, 130.79, 132.05, 138.80, 141.74, 144.53, 160.54, 201.95, 208.95;
LCMS (m/z): 265 (MþH)þ. Analysis calcd for C17H12O3: C, 77.26; H, 4.58.
Found: C, 77.09; H, 4.63. (* It is unresolved triplet).
174e175 ꢀC; IR (KBr): 3300,1695 cmꢃ1; 1H NMR (400 MHz):
n d 2.36
(s, 3H), 5.22 (s, 1H), 6.78 (d, 1H, J¼8.0 Hz), 6.81e6.90 (m, 1H), 6.96
(d, 1H, J¼7.6 Hz), 7.01 (d, 1H, J¼7.6 Hz), 7.08 (d, 1H, J¼8.0 Hz),
7.11e7.25 (m, 2H), 7.34e7.44 (m, 3H), 7.45e7.57 (m, 2H), 8.78 (s,
4.2.19. 10-Hydroxy-10-(cyclohex-2-enon-2-yl)-10H-phenanthren-9-
one (11). Yield: 70%; Rf (50% EtOAc in hexanes) 0.58; reaction time:
1H); 13C NMR (100 MHz):
d
21.20, 48.22, 109.98, 118.69, 120.74,
30 min, yellow solid; mp: 110e112 ꢀC; IR (KBr):
n
3431, 1703, 1668,
1.70e1.99 (m, 2H), 2.15e2.44 (m,
4H), 4.77 (s, 1H), 6.78 (t, 1H, J¼4.0 Hz), 7.33e7.48 (m, 3H), 7.57e7.70
(m, 2H), 7.82e7.95 (m, 3H); 13C NMR (100 MHz):
22.21, 26.09,
123.51, 126.50, 126.64, 126.85, 127.82, 128.43, 128.83, 129.28, 129.71,
133.34, 134.10, 142.26, 156.01, 178.05; LCMS (m/z): 316 (MþH)þ.
Analysis calcd for C21H17NO2: C, 79.98; H, 5.43; N, 4.44. Found: C,
79.85; H, 5.36; N, 4.53.
1601 cmꢃ1; 1H NMR (400 MHz):
d
d
38.74, 78.54, 122.86, 123.87, 127.71, 127.89, 128.53, 128.90, 129.19,
129.39, 130.85, 134.27, 136.76, 137.73, 140.88, 148.78, 198.56,
200.08; LCMS (m/z): 303 (MꢃH)þ. Analysis calcd for C20H16O3: C,
78.93; H, 5.30. Found: C, 78.81; H, 5.36.
4.2.14. 3-Hydroxy-3-(5,5-dimethylcyclohex-2-enon-2-yl)-1-methyl-
indolin-2-one (5). Yield: 91%; Rf (50% EtOAc in hexanes) 0.40; re-
action time: 7 h, white solid; mp: 144e146 ꢀC; IR (KBr):
n
3342,
1701, 1670, 1630, 1610 cmꢃ1; 1H NMR (400 MHz):
d
0.98 (s, 3H), 1.02
4.2.20. 10-Hydroxy-10-(5,5-dimethylcyclohex-2-enon-2-yl)-10H-
(s, 3H), 2.17 and 2.24 (ABq, 2H, J¼16.0 Hz), 2.36 (d, 2H, J¼4.0 Hz),
phenanthren-9-one (12). Yield: 79%; Rf (50% EtOAc in hexanes) 0.74;
3.22 (s, 3H), 4.02 (s, 1H), 6.84 (d, 1H, J¼7.6 Hz), 6.95e7.03 (m, 1H),
reaction time: 30 min, yellow solid; mp: 76e78 ꢀC; IR (KBr):
n 3429,

D. Basavaiah et al. / Tetrahedron 66 (2010) 5612e5622
5619
1705, 1668, 1599 cmꢃ1
;
1H NMR (400 MHz):
d
0.69 (s, 3H), 0.96 (s,
131.59, 134.22, 137.89, 145.53, 161.63, 198.36, 207.34; LCMS (m/z):
313 (MꢃH)þ. Analysis calcd for C21H14O3: C, 80.24; H, 4.49. Found:
C, 80.45; H, 4.43.
3H), 2.01e2.28 (m, 4H), 4.71 (s, 1H), 6.61 (t, 1H, J¼4.8 Hz), 7.32e7.48
(m, 3H), 7.57e7.70 (m, 2H), 7.81e7.90 (m, 3H); 13C NMR (100 MHz):
d
26.98, 28.59, 33.87, 40.03, 52.24, 78.56, 122.86, 123.96, 127.50,
127.67, 128.50, 128.89, 129.15, 129.60, 130.95, 134.17, 136.73, 137.58,
140.00, 146.78, 198.64, 200.35; LCMS (m/z): 331 (MꢃH)þ. Analysis
calcd for C22H20O3: C, 79.50; H, 6.06. Found: C, 79.39; H, 6.12.
4.2.25. 5-Hydroxy-5-(cyclopent-2-enon-5-yl)-5H-pyren-4-one
(16a)$. Yield: 19%; Rf (50% EtOAc in hexanes) 0.66; reaction time:
6 h, brown solid; mp: 160e162 ꢀC; IR (KBr):
n
3472, 1693 cmꢃ1; 1H
NMR (400 MHz):
d
2.09e2.40 and 2.70e3.01 (2 m, 3H)#, 4.48 and
4.2.21. 10-Hydroxy-10-(cyclopent-2-enon-2-yl)-10H-phenanthren-
5.46 (2s, 1H), 6.02e6.09 and 6.12e6.19 (2 m, 1H), 7.39e8.40 (m,
9H)# [The underlined peaks with low intensity may be due to the
presence of minor isomer of aldol adduct. (majoreminor¼76:24).
#also contains peaks belonging to the minor product]; 13C NMR
9-one (13). Yield: 72%; Rf (50% EtOAc in hexanes) 0.53; reaction
time: 1 h, gray solid; mp: 108e110 ꢀC; IR (KBr):
n
3466, 1699, 1682,
1599 cmꢃ1 1H NMR (400 MHz):
; d 2.22e2.47 (m, 4H), 5.40 (s, 1H),
6.97 (s, 1H) [unresolved triplet], 7.33e7.50 (m, 3H), 7.60e7.70 (m,
1H), 7.72e7.80 (m, 1H), 7.82e7.96 (m, 3H); 13C NMR (100 MHz):
(100 MHz): d 31.33, 31.52, 53.20, 54.81, 79.80, 80.78, 123.82, 123.94,
124.15, 126.04, 126.18, 126.45, 126.60, 126.73, 127.05, 127.22, 127.40,
127.48, 127.53, 127.83, 127.94, 128.14, 129.06, 129.34, 129.77, 130.11,
130.75, 131.19, 131.83, 132.05, 133.42, 134.13, 134.64, 135.75, 137.76,
139.80, 162.92, 164.54, 200.14, 203.22, 206.70, 207.98 (mixture of
diastereomers); LCMS (m/z): 313 (MꢃH)þ. $ tentatively assigned
structure.
d
26.15, 35.55, 77.76, 123.00, 123.97, 127.30, 128.07, 128.30, 128.65,
128.95, 129.59, 129.97, 134.91, 137.21, 137.83, 145.30, 162.17, 198.99,
207.16; LCMS (m/z): 289 (MꢃH)þ. Analysis calcd for C19H14O3: C,
78.61; H, 4.86. Found: C, 78.79; H, 4.91.
4.2.22. 5-Hydroxy-5-(cyclohex-2-enon-2-yl)-5H-pyren-4-one (14).
Yield: 61%; Rf (50% EtOAc in hexanes) 0.54; reaction time: 12 h,
4.2.26. 2-Hydroxy-2-(cyclohex-2-enon-2-yl)-2H-aceanthrylen-1-one
yellow solid; mp: 191e192 ꢀC; IR (KBr):
n
3391, 1668, 1662,
(17). Yield: 90%; Rf (50% EtOAc in hexanes) 0.59; reaction time: 6 h,
1620 cmꢃ1; 1H NMR (400 MHz):
d
1.81e2.05 (m, 2H), 2.18e2.52 (m,
yellow solid; mp: 204e206 ꢀC; IR (KBr):
n
3404, 1703, 1670,
4H), 4.02 (s, 1H), 7.18 (t, 1H, J¼4.0 Hz), 7.60e7.68 (m, 1H), 7.69e7.77
1649 cmꢃ1; 1H NMR (400 MHz):
d 1.89e2.07 (m, 2H), 2.27e2.52 (m,
(m, 2H), 7.78e7.84 (m, 2H), 7.86 (d, 1H, J¼7.6 Hz), 8.13 (d, 1H,
4H), 4.27 (s, 1H), 7.34 (t, 1H, J¼4.0 Hz), 7.42 (d, 1H, J¼6.8 Hz),
7.49e7.65 (m, 2H), 7.66e7.78 (m, 1H), 7.93 (d, 1H, J¼8.8 Hz), 8.12 (d,
1H, J¼8.4 Hz), 8.65 (s, 1H), 9.10 (d, 1H, J¼8.4 Hz); 13C NMR
J¼8.0 Hz), 8.36 (dd, 1H, J¼7.6, 0.8 Hz); 13C NMR (100 MHz):
d 22.30,
25.87, 38.47, 76.92, 124.71, 126.36, 126.46, 126.74, 127.03, 127.50,
127.59, 127.73, 128.16, 129.40, 131.22, 131.73, 133.97, 137.79, 142.65,
146.91, 198.35, 198.42; LCMS (m/z): 327 (MꢃH)þ. Analysis calcd for
C22H16O3: C, 80.47; H, 4.91. Found: C, 80.35; H, 4.84.
(100 MHz):
d 22.44, 25.97, 38.47, 80.29, 119.96, 124.65, 124.79,
125.90, 126.53, 127.66, 128.47, 128.74, 129.15, 129.38, 132.64, 133.72,
139.06, 140.18, 143.60, 148.16, 199.13, 202.76; LCMS (m/z): 327
(MꢃH)þ. Analysis calcd for C22H16O3: C, 80.47; H, 4.91. Found: C,
80.59; H, 4.99.
4.2.23. 5-Hydroxy-5-(5,5-dimethylcyclohex-2-enon-2-yl)-5H-pyren-
4-one (15). This BeH adduct was obtained as a major product along
with a minor side product in 70:30 ratio (on the basis of NMR
studies) in 67% isolated (mixture) yield. This was used as such for
the next step. Rf (50% EtOAc in hexanes) 0.64; Reaction time: 48 h,
4.2.27. 2-Hydroxy-2-(5,5-dimethylcyclohex-2-enon-2-yl)-2H-acean-
thrylen-1-one (18). Yield: 85%; Rf (50% EtOAc in hexanes) 0.71; re-
action time: 24 h, yellow solid; mp: 176e178 ꢀC; IR (KBr):
n
3404,
yellow solid; mp: 172e174 ꢀC; IR (KBr):
n
3429, 1693, 1658,
1707, 1668, 1620 cmꢃ1 1H NMR (400 MHz):
; d 1.00 (s, 3H), 1.03 (s,
1620 cmꢃ1; 1H NMR (400 MHz):
d
0.90 (s, 3H), 1.01 (s, 3H), 2.09 and
3H), 2.20 and 2.25 (ABq, 2H, J¼16.4 Hz), 2.35 (d, 2H, J¼4.4 Hz), 4.13
(s, 1H), 7.22 (t, 1H, J¼4.4 Hz), 7.43 (d, 1H, J¼6.4 Hz), 7.52e7.67 (m,
2H), 7.69e7.80 (m, 1H), 7.95 (d, 1H, J¼8.8 Hz), 8.14 (d, 1H, J¼8.4 Hz),
2.17 (ABq, 2H, J¼16.0 Hz), 2.27 and 2.35 (dABq, 2H, J¼4.0, 19.2 Hz),
3.95 (s, 1H), 7.08 (t, 1H, J¼4.0 Hz), 7.59e7.96 (m, 6H)*, 8.13 (d, 1H,
J¼8.0 Hz), 8.35 (d,1H, J¼7.2 Hz). In addition to the above peaks (due
8.67 (s, 1H), 9.12 (d, 1H, J¼8.8 Hz); 13C NMR (100 MHz):
d 28.13,
to the BayliseHillman adduct) peaks at
d
1.15 (s), 1.23 (s), 2.52 and
28.19, 34.04, 39.99, 52.01, 80.14, 119.77, 124.70, 124.82, 125.90,
126.51, 127.64, 128.50, 128.72, 129.10, 129.36, 132.59, 133.69, 138.18,
140.19, 143.63, 145.78, 199.12, 202.69; LCMS (m/z): 355 (MꢃH)þ.
Analysis calcd for C24H20O3: C, 80.88; H, 5.66. Found: C, 80.71; H,
5.72.
2.57 (ABq, J¼16.0 Hz), 3.65 (s), 7.14 (s), 8.19 (d, J¼8.0 Hz), 8.41 (d,
J¼7.2 Hz) appeared and these are attributed to the side product.
*This multiplet also contains peaks relating to the side product; 13C
NMR (100 MHz):
d 25.44, 26.07, 28.10, 34.09, 39.90, 46.02, 51.96,
75.39, 76.74, 124.27, 124.71, 126.32, 126.48, 126.74, 126.81, 126.95,
127.03, 127.14, 127.22, 127.51, 127.56, 127.59, 127.71, 128.19, 129.01,
129.33, 129.41, 131.23, 131.43, 131.79, 132.17, 133.98, 134.73, 134.91,
135.95, 137.71, 141.75, 144.66, 154.98, 196.67, 197.13, 198.31, 198.44,
202.97 (mixture of two compounds).
4.2.28. 2-Hydroxy-2-(cyclopent-2-enon-2-yl)-2H-aceanthrylen-1-
one (19). Yield: 70%; Rf (50% EtOAc in hexanes) 0.43; reaction time:
10 h, dark solid; mp: 216e217 ꢀC; IR (KBr): 3501, 1693, 1620 cmꢃ1
n ;
1H NMR (400 MHz):
d 2.46e2.54 (m, 2H), 2.56e2.64 (m, 2H), 5.01
(br s, 1H), 7.35 (t, 1H, J¼4.0 Hz), 7.56e7.69 (m, 3H), 7.71e7.81 (m,
4.2.24. 5-Hydroxy-5-(cyclopent-2-enon-2-yl)-5H-pyren-4-one (16).
Reaction between pyrene-(4,5)-dione (7c) and cyclopent-2-enone
(1c) following the procedure as described for compound 3a pro-
vided the desired BeH alcohol (16) as a major product in 53% iso-
lated yield along with the minor product (presumably aldol
product) (16a) in 19% isolated yield (these were separated by silica
gel column chromatography using 30% EtOAc in hexanes as a sol-
vent system). Yield: 53%; Rf (50% EtOAc in hexanes) 0.48; reaction
1H), 7.99 (dd, 1H, J¼1.6, 7.2 Hz), 8.15 (d, 1H, J¼8.4 Hz), 8.71 (s, 1H),
9.10 (d, 1H, J¼8.8 Hz); 13C NMR (100 MHz):
d 26.80, 35.40, 79.34,
120.87, 123.69, 124.79, 126.07, 126.76, 127.94, 128.40, 128.81, 129.46,
129.51, 133.26, 133.75, 139.18, 143.89, 144.44, 160.42, 201.85,
209.25; LCMS (m/z): 315 (MþH)þ. Analysis calcd for C21H14O3: C,
80.24; H, 4.49. Found: C, 80.44; H, 4.53.
4.2.29. 2-(2-Hydroxyphenyl)-2H-acenaphthylen-1-one
(20). This
time: 6 h, brown solid; mp: 77e79 ꢀC; IR (KBr):
n
3458, 1693, 1680,
compound was prepared following the same procedure as de-
1620 cmꢃ1 1H NMR (400 MHz):
;
d
2.19e2.45 (m, 4H), 5.64 (s, 1H),
scribed for compound 4a: Yield: 73%; Rf (20% EtOAc in hexanes)
6.64e6.72 (m,1H), 7.63e7.73 (m, 2H), 7.74e7.84 (m, 2H), 7.87 (d,1H,
J¼8.0 Hz), 7.94 (d, 1H, J¼7.6 Hz), 8.10 (d, 1H, J¼8.0 Hz), 8.24 (d, 1H,
0.47; white solid; mp: 194e196 ꢀC; IR (KBr): 3287, 1695 cmꢃ1; 1H
n
NMR (400 MHz):
d 5.43 (s, 1H), 6.76e6.85 (m, 1H), 6.89 (d, 1H,
J¼7.2 Hz); 13C NMR (100 MHz):
d
26.13, 35.54, 78.60, 124.13, 125.81,
J¼7.6 Hz), 7.08 (d, 1H, J¼7.6 Hz), 7.15e7.23 (m, 1H), 7.55 (d, 1H,
126.35, 127.01, 127.05, 127.15, 127.58, 127.97, 128.17, 129.54, 131.00,
J¼6.8 Hz), 7.66e7.85 (m, 2H), 7.93 (d, 1H, J¼8.4 Hz), 7.98e8.04 (m,

5620
D. Basavaiah et al. / Tetrahedron 66 (2010) 5612e5622
2H), 8.19 (d, 1H, J¼8.0 Hz); 13C NMR (100 MHz):
d
53.98, 118.79,
209e211 ꢀC; IR (KBr): 1699, 1618 cmꢃ1 1H NMR (400 MHz):
n ;
121.08,122.98,123.03,124.80,124.84,127.99,128.54,128.79,129.09,
131.09, 132.14, 132.72, 136.46, 143.12, 155.59, 206.67; LCMS (m/z):
261 (MþH)þ. Analysis calcd for C18H12O2: C, 83.06; H, 4.65. Found:
C, 82.90; H, 4.71.
d 3.00e3.12 (m, 4H), 7.52e7.72 (m, 4H), 8.02e8.11 (m, 1H),
8.49e8.60 (m, 2H), 8.63 (d, 1H, J¼7.6 Hz); 13C NMR (100 MHz):
d
22.82, 41.62, 116.19, 120.38, 121.89, 122.87, 123.40, 126.19, 126.31,
126.46, 126.78, 127.05, 127.47, 127.98, 128.14, 129.52, 154.96, 184.27,
194.69; LCMS (m/z): 273 (MþH)þ. Analysis calcd for C19H12O2: C,
83.81; H, 4.44. Found: C, 83.75; H, 4.48.
4.2.29.1. Crystal data for 20. Empirical formula, C18H12O2; for-
mula weight, 260.28; crystal color, habit: colorless, block; crystal
dimensions, 0.50ꢂ0.28ꢂ0.26 mm3; crystal system, triclinic; lattice
4.2.32.1. Crystal data for 23. Empirical formula, C19H12O2; for-
mula weight, 272.29; crystal color, habit: yellow, plate; crystal di-
mensions, 0.25ꢂ0.18ꢂ0.15 mm3; crystal system, monoclinic; lattice
ꢀ
type, primitive; lattice parameters, a¼7.9386 (16) A, b¼8.9357
ꢀ
ꢀ
a
(18) A, c¼10.627 (2) A;
¼68.928 (3);
b
¼79.267 (3); ¼65.496 (3);
g
V¼639.5 (2) A ; space group, Pꢃ1; Z¼2; Dcalcd¼1.352 g/cm3;
type, centro symmetric; lattice parameters, a¼24.610 (2) A,
3
ꢀ
ꢀ
(Mo Ka)¼0.71073 A; R (Iꢄ2s1)¼0.0405, wR2¼0.1069.
b¼5.4124 (4) A, c¼19.5981 (16) A;
a
¼90.00,
b
¼95.0210 (10);
ꢀ
ꢀ
ꢀ
F000¼272;
l
3
ꢀ
Detailed X-ray crystallographic data is available from the Cam-
bridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2
1EZ, UK (for compound 20 CCDC # 753,491).
g
¼90.00; V¼2600.4 (4) A ; space group, C2/c; Z¼8; Dcalcd¼1.391 g/
ꢀ
cm3; F000¼1136;
l
(Mo Ka)¼0.71073 A;
R
(Iꢄ2s1)¼0.0434,
wR2¼0.0945. Detailed X-ray crystallographic data is available from
the Cambridge Crystallographic Data Centre, 12 Union Road, Cam-
bridge CB2 1EZ, UK (for compound 23 CCDC # 754,880).
4.2.30. Representative procedure: synthesis of 2-oxapentacyclo
[15.4.0.0.3,160.4,90.10,15]henicosan-1(17),3(16),
4(9),5,7,10(15),11,13-
octaen-18-one (21). To a stirred solution of 10-hydroxy-10-(cyclo-
hex-2-enon-2-yl)-10H-phenanthren-9-one (11) (1 mmol, 0.304 g)
in dichloroethane (2 mL) methanesulfonic acid (1 mmol, 0.096 g,
0.065 mL) was added at room temperature (25e28 ꢀC) and the
reaction mixture was heated under reflux for 30 min. The reaction
mixture was allowed to cool to room temperature and diluted with
water (3 mL) and extracted with CH2Cl2 (3ꢂ5 mL). Combined or-
ganic layer was dried over anhydrous Na2SO4. Solvent was evapo-
rated and the residue, thus obtained, was subjected to column
chromatography (silica gel, 5% ethyl acetate in hexanes) to provide
the desired product (21) as yellow solid in 86% (0.247 g) isolated
4.2.33. 2-Oxahexacyclo[15.4.0.0.3,161.4,82.4(8),112.4(8),15]tricosane-1
(17),3(16),4(22),5,7,9,11,13,15(23)-nonaen-18-one (24). Yield: 50%;
Rf (20% EtOAc in hexanes) 0.45; reaction time: 30 min, yellow solid;
mp: 181e183 ꢀC; IR (KBr):
n ;
1662, 1618 cmꢃ1 1H NMR (400 MHz):
d
2.26e2.42 (m, 2H), 2.73 (t, 2H, J¼6.0 Hz), 3.11 (t, 2H, J¼6.0 Hz),
7.89e8.20 (m, 6H), 8.31 (d, 1H, J¼7.6 Hz), 9.85 (d, 1H, J¼8.0 Hz); 13C
NMR (100 MHz): d 22.32, 24.45, 39.21,116.93,118.08,119.88,120.66,
123.06, 123.63, 124.81, 125.26, 125.86, 126.32, 126.39, 126.47,
126.69, 128.46, 131.38, 131.63, 149.38, 169.70, 194.38; LCMS (m/z):
311 (MþH)þ. Analysis calcd for C22H14O2: C, 85.14; H, 4.55. Found: C,
85.25; H, 4.49.
yield. Rf (20% EtOAc in hexanes) 0.44; mp: 160e162 ꢀC; IR (KBr):
n
1666, 1618 cmꢃ1; 1H NMR (400 MHz):
d
2.18e2.34 (m, 2H), 2.66 (t,
4.2.34. 20,20-Dimethyl-2-oxahexacyclo[15.4.0.0.3,161.4,82.4(8),11 2.4
(8),15]tricosane-1(17),3(16),4(22),5,7,9,11,13,15(23)-nonaen-18-one
(25). The BayliseHillman alcohol (15) was used as such [along with
the minor side product (30%)] and the yield of fused furan 25 is
calculated on the basis of actual amount of alcohol present. Yield:
43%; Rf (20% EtOAc in hexanes) 0.67; reaction time: 60 min, white
2H, J¼6.0 Hz), 3.04 (t, 2H, J¼6.0 Hz), 7.53e7.64 (m, 3H), 7.65e7.73
(m, 1H), 8.09e8.20 (m, 1H), 8.52e8.68 (m, 2H), 9.62 (d, 1H,
J¼8.0 Hz); 13C NMR (100 MHz):
d 22.19, 24.36, 39.18, 117.37, 119.50,
120.41, 121.34, 122.85, 123.24, 125.80, 126.37, 126.90, 127.14, 127.36,
128.47, 128.77, 129.54, 148.75, 169.53, 194.28; LCMS (m/z): 287
(MþH)þ. Analysis calcd for C20H14O2: C, 83.90; H, 4.93. Found: C,
83.73; H, 4.88.
solid; mp: 216e218 ꢀC; IR (KBr):
n ;
1664, 1610 cmꢃ1 1H NMR
(400 MHz):
d 1.25 (s, 6H), 2.61 (s, 2H), 3.02 (s, 2H), 7.96e8.22 (m,
6H), 8.44 (d, 1H, J¼7.6 Hz), 9.89 (d, 1H, J¼8.0 Hz); 13C NMR
4.2.30.1. Crystal data for 21. Empirical formula, C20H14O2; for-
mula weight, 286.31; crystal color, habit: colorless, block; crystal
dimensions, 0.28ꢂ0.25ꢂ0.18 mm3; crystal system, monoclinic;
(100 MHz): d 28.61, 34.87, 38.34, 53.49, 117.03, 118.16, 118.84,
120.88, 123.16, 123.69, 124.90, 125.36, 126.00,126.44, 126.51, 126.81,
128.54, 131.48, 131.76, 149.87, 168.94, 193.92; LCMS (m/z): 339
(MþH)þ. Analysis calcd for C24H18O2: C, 85.18; H, 5.36. Found: C,
85.00; H, 5.41.
ꢀ
lattice type, primitive; lattice parameters, a¼7.5443 (7) A,
ꢀ
ꢀ
b¼18.8155 (17) A, c¼10.1375 (9) A;
a
¼90.00,
b¼106.017 (2);
3
ꢀ
g
¼90.00; V¼1383.2 (2) A ; space group, P2 (1); Z¼4;
ꢀ
Dcalcd¼1.375 g/cm3; F000¼600;
l
(Mo Ka)¼0.71073 A; R (Iꢄ2s1)¼
4.2.35. 2-Oxahexacyclo[15.3.0.0.3,161.4,82.4(8),112.4(8),15]docosane
-1
0.0418, wR2¼0.0838. Detailed X-ray crystallographic data is avail-
able from the Cambridge Crystallographic Data Centre, 12 Union
Road, Cambridge CB2 1EZ, UK (for compound 21 CCDC # 754,879).
(17),3(16),4(21),5,7,9,11,13,15(22)-nonaen-18-one (26). Yield: 20%;
Rf (20% EtOAc in hexanes) 0.33; reaction time: 60 min, yellow solid;
mp: 185e186 ꢀC; IR (KBr): 1693, 1600 cmꢃ1; 1H NMR (400 MHz):
n
d
3.05e3.17 (m, 4H), 7.88e8.06 (m, 4H), 8.07e8.17 (m, 2H), 8.24 (d,
4.2.31. 20,20-Dimethyl-2-oxapentacyclo[15.4.0.0.3,160.4,90.10,15]henico-
san-1(17),3(16),4(9),5,7,10(15),11,13-octaen-18-one (22). Yield: 89%;
Rf (20% EtOAc in hexanes) 0.63; reaction time: 30 min, white solid;
1H, J¼7.6 Hz), 8.84 (d, 1H, J¼7.6 Hz); 13C NMR (100 MHz):
d 22.94,
41.68, 116.67, 117.14, 121.07, 122.48, 123.59, 125.08, 125.19, 125.21,
125.68, 126.02, 126.62, 127.15, 128.11, 131.34, 131.66, 155.54, 184.40,
194.82; LCMS (m/z): 297 (MþH)þ. Analysis calcd for C21H12O2: C,
85.12; H, 4.08. Found: C, 85.02; H, 4.15.
mp: 178e180 ꢀC; IR (KBr): 1,666, 1,610 cmꢃ1; 1H NMR (400 MHz):
n
d
1.22 (s, 6H), 2.57 (s, 2H), 2.97 (s, 2H), 7.58e7.67 (m, 3H), 7.68e7.76
(m, 1H), 8.20e8.28 (m, 1H), 8.63e8.73 (m, 2H), 9.65 (dd, 1H, J¼0.8,
8.0 Hz); 13C NMR (100 MHz):
28.47, 34.65, 38.12, 53.36, 117.36,
d
4.2.36. Representative procedure: synthesis of {2-oxaheptacyclo-
[20.4.0.0.3,210.4,130.8,130.12,13 0.14,19]hexacosane-1(22),4,6,8(13),9,11,14
(19)-heptaen-18,23-dione}-20-spiro-10-acenaphthylen-20-one (27)
(Racemic compound with cis-cis-cis configuration)17. To a stirred
solution of 2-hydroxy-2-(cyclohex-2-enon-2-yl)-2H-acenaph-
thylen-1-one (8) (1 mmol, 0.278 g) in dichloroethane (2 mL)
methanesulfonic acid (3 mmol, 0.288 g, 0.194 mL) was added at
room temperature (25e28 ꢀC) and the reaction mixture was
heated under reflux for 1 h. The reaction mixture was allowed to
118.36, 120.44, 121.43, 122.90, 123.29, 125.87, 126.37, 126.95, 127.21,
127.41, 128.50, 128.79, 129.48, 149.14, 168.66, 193.70; LCMS (m/z):
315 (MþH)þ. Analysis calcd for C22H18O2: C, 84.05; H, 5.77. Found:
C, 84.12; H, 5.71.
4.2.32. 2-Oxapentacyclo[15.3.0.0.3,160.4,90.10,15]cosan-1(17), 3(16),4
(9),5,7,10(15),11,13-octaen-18-one (23). Yield: 96%; Rf (20% EtOAc in
hexanes) 0.42; reaction time: 30 min, brown solid; mp:

D. Basavaiah et al. / Tetrahedron 66 (2010) 5612e5622
5621
cool to room temperature and diluted with water (3 mL) and
References and notes
extracted with CH2Cl2 (3ꢂ5 mL). Combined organic layer was
dried over anhydrous Na2SO4. Solvent was evaporated and the
residue, thus obtained, was subjected to column chromatography
(silica gel, 45% ethyl acetate in hexanes) to provide the desired
product (27) as white solid in 65% (0.169 g) isolated yield. Rf (50%
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EtOAc in hexanes) 0.47; mp: 280 ꢀC (dec); IR (KBr):
n 1726, 1684,
1.72e2.05 (m, 4H),
1653, 1614 cmꢃ1 1H NMR (400 MHz):
;
d
2.10e2.46 (m, 5H), 2.52e2.70 (m, 1H), 2.91e3.24 (m, 2H), 7.06 (d,
1H, J¼6.8 Hz), 7.27 (d, 1H, J¼6.4 Hz), 7.37e7.44 (m, 1H), 7.46e7.55
(m, 1H), 7.56e7.65 (m, 1H), 7.67 (d, 1H, J¼8.0 Hz), 7.71 (d, 1H,
J¼6.8 Hz), 7.74e7.81 (m, 1H), 7.82e7.91 (m, 2H), 7.94 (d, 1H,
J¼7.2 Hz), 8.13 (d, 1H, J¼8.0 Hz); 13C NMR (100 MHz):
d 21.29,
22.85, 22.95, 24.61, 36.42, 37.90, 69.95, 74.69, 113.50, 116.77, 120.18,
120.58, 121.97, 123.86, 125.00, 127.14, 127.56, 128.30, 128.84,
130.56, 131.55, 131.88, 133.51, 137.30, 137.88, 140.97, 141.65, 142.27,
142.84, 158.94, 174.70, 192.64, 195.72, 201.99; 13C NMR (DMSO-d6,
100 MHz):
d 20.81, 22.24, 22.60, 23.72, 35.90, 37.43, 69.36, 73.98,
112.70, 115.51, 120.99, 121.08, 121.34,122.94, 123.53,124.49, 126.78,
127.74, 128.10, 128.17, 128.33, 130.02, 131.23, 131.44, 133.03, 136.56,
137.51, 139.87, 141.20, 142.03, 142.28, 159.44, 175.22, 192.18, 195.82,
201.70; LCMS (m/z): 519 (MꢃH)þ. Analysis calcd for C36H24O4: C,
83.06; H, 4.65. Found: C, 83.13; H, 4.62.
4.2.36.1. Crystal data for 27. Empirical formula, C37H26Cl2O4;
*
formula weight, 605.48; crystal color, habit: colorless, block; crystal
dimensions, 0.41ꢂ0.35ꢂ0.25 mm3; crystal system, monoclinic;
ꢀ
lattice type, primitive; lattice parameters, a¼11.0046 (13) A,
ꢀ
ꢀ
b¼24.044 (3) A, c¼11.4448 (13) A;
a
¼90.00,
b
¼97.252 (2);
3
ꢀ
g
¼90.00; V¼3004.0 (6) A ; space group, P2 (1)/n; Z¼4;
ꢀ
Dcalcd¼1.339 g/cm3; F000¼1256;
l
(Mo Ka)¼0.71073 A; R (Iꢄ2s1)¼
0.0911, wR2¼0.2574. Detailed X-ray crystallographic data is avail-
able from the Cambridge Crystallographic Data Centre, 12 Union
Road, Cambridge CB2 1EZ, UK (for compound 27 CCDC # 754,881).
*Crystal contains one disordered CH2Cl2 molecule.
4.2.37. {16,16,25,25-Tetramethyl-2-oxaheptacyclo[20.4.0.0.3,210.4,13
0.8,130.12,130.14,19]hexacosane-1(22),4,6,8(13),9,11,14(19)-heptaen-
18,23-dione}-20-spiro-10-acenaphthylen-20-one (28) (racemic
compound with cis-cis-cis configuration)17. Yield: 58%; Rf (50%
EtOAc in hexanes) 0.66; reaction time: 1 h, yellow solid; mp:
196e198 ꢀC; IR (KBr):
(400 MHz): 0.67 (s, 3H), 1.10 (s, 3H), 1.11 (s, 3H), 1.21 (s, 3H), 1.66
n ;
1724, 1682, 1664, 1616 cmꢃ1 1H NMR
d
and 1.84 (ABq, 2H, J¼16.0 Hz), 2.10e2.28 (m, 3H)*, 2.47 (d, 1H,
J¼18.0 Hz)*, 2.91 and 2.97 (ABq, 2H, J¼18.0 Hz), 7.03 (d, 1H,
J¼6.8 Hz), 7.20 (d, 1H, J¼7.2 Hz), 7.32e7.40 (m, 1H), 7.42e7.51 (m,
1H), 7.53e7.67 (m, 2H), 7.68e7.79 (m, 2H), 7.80e7.93 (m, 3H), 8.11
5. (a) Hewawasam, P.; Erway, M.; Moon, S. L.; Knipe, J.; Weiner, H.; Boissard, C. G.;
Post-Munson, D. J.; Gao, Q.; Huang, S.; Gribkoff, V. K.; Meanwell, N. A. J. Med.
Chem. 2002, 45, 1487e1499; (b) Hewawasam, P.; Gribkoff, V. K.; Pendri, Y.;
Dworetzky, S. I.; Meanwell, N. A.; Martinez, E.; Boissard, C. G.; Post-Munson, D.
J.; Trojnacki, J. T.; Yeleswaram, K.; Pajor, L. M.; Knipe, J.; Gao, Q.; Perrone, R., Jr.;
Starrett, J. E. Bioorg. Med. Chem. Lett. 2002, 12, 1023e1026; (c) Hewawasam, P.;
Meanwell, N. A.; Gribkoff, V. K.; Dworetzky, S. I.; Boissard, C. G. Bioorg. Med.
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Hume, W. E.; Umezome, T.; Okazaki, K.; Ueki, Y.; Kumagai, K.; Hourai, S.;
Nagamine, J.; Seki, H.; Taiji, M.; Noguchi, H.; Nagata, R. J. Med. Chem. 2001,
44, 4641e4649.
(d, 1H, J¼8.0 Hz) [*The doublet at
two peaks merged with the multiplet at
(100 MHz): 27.54, 28.09, 29.37, 29.75, 33.48, 34.99, 36.92, 38.30,
d
2.47 is part of ABq whose other
d
2.10e2.28]; 13C NMR
d
50.98, 51.76, 69.70, 74.98, 113.54, 115.40, 120.03, 120.51, 121.90,
123.40, 123.87, 124.95, 127.10, 127.38, 127.51, 128.24, 128.81, 130.63,
131.52, 131.88, 133.52, 137.17, 138.03, 139.79, 141.46, 142.45, 142.82,
157.04, 173.89, 192.17, 195.65, 201.80; LCMS (m/z): 577 (MþH)þ.
Analysis calcd for C40H32O4: C, 83.31; H, 5.59. Found: C, 83.41; H,
5.51.
7. (a) Anderson, J. C.; Denton, R. M.; Wilson, C. Org. Lett. 2005, 7, 123e125; (b) Xu,
M.; Deng, Z.; Li, M.; Li, J.; Fu, H.; Proksch, P.; Lin, W. J. Nat. Prod. 2004, 67,
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Trost, B. M.; Tang, W. Angew. Chem., Int. Ed. 2002, 41, 2795e2797.
8. Lee, K.-I.; Park, Y.; Park, S.-J.; Hwang, J.-H.; Lee, S.-J.; Kim, G.-D.; Park, W.-K.; Lee, S.;
Jeong,D.; Kong, J.-Y.;Kang, H.-K.;Cho, H. Bioorg. Med. Chem.Lett. 2006,16, 737e742.
9. Rhee, H.-K.; Park, H. J.; Lee, S. K.; Lee, C.-O.; Choo, H.-Y. P. Bioorg. Med. Chem.
2007, 15, 1651e1658.
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N.; Chou, T.-C. J. Med. Chem. 1993, 36, 4108e4112.
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Magnus, P.; Turnbull, R. Org. Lett. 2005, 7, 4531e4534; (c) Lee, S.; Hartwig, J. F. J.
Org. Chem. 2001, 66, 3402e3415; (d) Hewawasam, P.; Erway, M. Tetrahedron Lett.
1998, 39, 3981e3984; (e) Goehring, R. R.; Sachdeva, Y. P.; Pisipati, J. S.; Sleevi,
M. C.; Wolfe, J. F. J. Am. Chem. Soc. 1985, 107, 435e443.
Acknowledgements
We thank DST (New Delhi) for funding this project. SR and UD
thank CSIR (New Delhi) for their research fellowships. We thank
UGC (New Delhi) for support and providing some instrumental
facilities. We thank National single crystal X-ray facility funded
by DST. We also thank Prof. S. Pal, School of Chemistry, University
of Hyderabad for helpful discussions regarding X-ray data
analysis.
12. Malona, J. A.; Colbourne, J. M.; Frontier, A. J. Org. Lett. 2006, 8, 5661e5664.

5622
D. Basavaiah et al. / Tetrahedron 66 (2010) 5612e5622
13. Basavaiah, D.; Sreenivasulu, B.; Jaganmohan Rao, A. J. Org. Chem. 2003, 68,
5983e5991.
14. Sodium methoxide mediated BeH coupling of cyclo alkenones with isatin
derivatives is known in the literature, see: Luo, S.; Mi, X.; Xu, H.; Wang, P. G.;
Cheng, J.-P. J. Org. Chem. 2004, 69, 8413e8422.
17. cis-cis-cis-Stereochemistry is assigned to the compounds 27 and 28 as they
contain CeC bonds (C3eC4, C12eC21, C10eC20), connecting acenaphthene
rings, on the same side. Compounds 27 and 28 are racemic [1:1 mixture of
compounds with 3R,20(10)R,21S, and 3S,20(10)S,21R stereochemistry] and only
one form is shown in the structures.
15. Detailed X-ray crystallographic data is available from the CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK. CCDC numbers for compounds 4b, 4c, 4g, 20, 21, 23,
and 27 are 753,488, 753,489, 753,490, 753,491, 754,879, 754,880, and 754,881,
respectively.
16. The TiCl4-mediated BeH reaction between aromatic 1,2-diones [(9,10)-phe-
nanthrenedione and pyrene-(4,5)-dione] and alkyl vinyl ketones at room
temperature (35e37 ꢀC) (summer time room temperature in Hyderabad) pro-
vided fused furan derivatives. Ref: Basavaiah, D.; Sreenivasulu, B.; Rao, J. S.
Tetrahedron Lett. 2001, 42, 1147e1149. During the present study, we noticed that
the TiCl4-mediated BeH reaction of [9,10]-phenanthrenedione with MVK at
25e28 ꢀC (winter time room temperature in Hyderabad) for 3 h provided the
fused furan derivatives (40%) along with the corresponding BeH alcohols (30%).
At 35 ꢀC we obtained the fused furan derivative in 68% isolated yield.
18. Single crystal of 27 contains one disordered CH2Cl2 molecule.
19. 13C NMR spectrum of the compound 27 in CDCl3 showed 34 signals in which
two signals, at d 123.86 and d 127.14, were more intense (long peaks) indicating
that each of these signals arose due to two carbons (total four carbons). Thus
total number of signals (36) and total number of carbons (36) match perfectly.
This has been further confirmed when we recorded 13C NMR spectrum of the
compound 27 in DMSO-d6, which showed 36 signals for 36 carbons. From these
studies it looks clear that one of the quaternary aliphatic carbons (probably C-3
because it is benzylic, allylic, tertiary and
region (beyond 113.00).
a to oxygen) appears at downfield
d
20. We thank one of the referees for suggestions in understanding the stereo-
chemistry of these compounds.
21. Structure of this compound 28 was assigned in analogy with that of 27.