SnCl4 or TiCl4: Highly efficient catalysts for the detetrahydropyranylation and demethoxymethylation of phenolic ethers and sequential one-pot asymmetric synthesis of 3-aryl-2-hydroxy-2,3-dihydroindan-1-ones from chalcone epoxides

Article abstract of DOI:10.1039/c5ra10499h

SnCl₄ or TiCl₄ catalysts provided a rapid and efficient detetrahydropyranylation and demethoxymethylation of phenolic ethers and a sequential one-pot intramolecular Friedel-Crafts alkylation of chalcone epoxides under mild reaction c

Full text of DOI:10.1039/c5ra10499h

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SnCl or TiCl : highly efficient catalysts for the
4
4
detetrahydropyranylation and
Cite this: RSC Adv., 2015, 5, 63095
demethoxymethylation of phenolic ethers and
sequential one-pot asymmetric synthesis of 3-aryl-
2-hydroxy-2,3-dihydroindan-1-ones from
chalcone epoxides†
a
a
b
Naseem Ahmed,* Gulab Khushalrao Pathe and Sohan Jheeta
4 4
SnCl or TiCl catalysts provided a rapid and efficient detetrahydropyranylation and demethoxymethylation
of phenolic ethers and a sequential one-pot intramolecular Friedel–Crafts alkylation of chalcone epoxides
under mild reaction conditions. The reaction took 2–3 min to give the phenols and 1-indanones in an
Received 3rd June 2015
Accepted 10th July 2015
ꢀ
excellent yield (90–98%) at 0 C without affecting other functional groups. With these catalysts, our
DOI: 10.1039/c5ra10499h
protocol gave regioselective products as trans-3-aryl-2-hydroxy-1-indanones in an excellent yield (76–
www.rsc.org/advances
98%) and an enantiomeric excess of up to 99.9% under the same conditions.
5
6
7
8
9
10
11
etherate, LiBr, LiBF , LiOTf, LiClO , Sc(OTf) , In(OTf)3,
4
14
4
3
Introduction
12
13
15
16
I
2
,
InCl
3
7
,
ZrCl
4
,
CuCl
2
,
4
the salt NH Cl, expansive
1
18
19
The protection and deprotection of functional groups are the graphite, clay materials, silica-supported sulfuric acid, and
2
0–26
most frequently used strategies in multi-step organic synthesis. other miscellaneous catalysts.
In particular, the protection and deprotection of hydroxyl have been used for the demethoxymethylation of alcohols and
groups are extremely important because of their enormous phenols; these catalysts include HCl, BBr pyridinium
demand for the synthesis of a number of compounds of bio- p-toluene sulphonate under strong acidic conditions, mild
Similarly, many catalysts
3
,
logical and synthetic interest such as carbohydrates, macro- Lewis acids such as ZnBr
and TiCl
BBr, and (i-PrS) BBr. Most of these
2
in aprotic conditions and
2
4
1
27
lides, peptides, steroids, nucleotides and polyethers. The BBr
derivatives like Me
3
2
protection of a hydroxyl group with 3,4-dihydro-2H-pyran (DHP) methods have different drawbacks such as long reaction times,
and methoxymethyl chloride (MOMCl) are the most frequently low yields, reuxes at high temperature and tedious workup
used methods due to the stability of the resulting 2-tetrahy- procedures. Hence, there is still scope to develop more
dropyranyl ethers (THPEs) and the methoxymethyl ethers straightforward and efficient methods for the deprotection of
(
MOMEs) respectively in the presence of strong bases or tetrahydropyranyl and methoxymethyl ethers.
nucleophiles such as Grignard reagents, organolithium
Indan-1-one and indan-2-one derivatives are important
compounds, metal hydrides, catalytic hydrogenation, and moieties in the core structures of many natural products,
2
,3
28
28a–c
alkylating and acylating agents.
Conversely, the deprotection of the THP and MOM ethers indanoyl isoleucine conjugates,
agrochemicals and medicines including indacrinone,
28d
28e
indanocines,
quad-
28f,g
28h,i
29
requires efficient methods to avoid the decomposition and/or ranglularin A,
parthenocissin A,
(+)-pauciorol F, nor-
30
31a–c
loss of other functional groups in the product under harsh diterpene taiwaniaquinol B, sulindac, NSAID,
NMDA
melatonin pre-
31d
31e
reaction conditions. Therefore, many catalysts have been receptor antagonists,
explored for the detetrahydropyranylation of alcohols and cursor,
phenols including protic acids, Lewis acids such as BF
benzodiazepines,
31f,g
32,33
and neoavonoids
(Fig. 1). They are also reported
4
34
3
-
as being in higher plants such as Uvaria afzelii roots, Pteridium
34c
34d
aquilinum and Equisetum arvense and have been screened
for various biological activities including those for cancer and
Alzheimer’s diseases. 2-(Alkoxycarbonyl)- and 2-acetyl-1-
indanones are present in cytotoxic natural compound pter-
the potent and selective COX-2 inhibitor osu-
and the acetylcholinesterase inhibitor donepezil
hydrochloride. They are approved by the US-FDA for the
a
Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee-247 667,
Uttarakhand, India. E-mail: nasemfcy@iitr.ac.in; Fax: +91 1332 285745; Tel: +91
1
332 285745
2
8,29
b
NoR HGT & LUCA, 1 Scott Hall Crescent, Leeds, LS7 3RB, UK
osines,
3
0,32
†
Electronic supplementary information (ESI) available: Experimental procedures, lide,
1
13
characterization data and H,
0.1039/c5ra10499h
C
NMR spectra associated. See DOI:
30
1
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29
treatment of mild to moderate Alzheimer’s disease. Similarly, Table 1 Optimization of catalysts in the synthesis of indanones via a
one-pot deprotection and cyclization reaction
the enantiomerically pure derivative, 1-amino-2-indanol is a key
precursor of the chiral ligand and the chiral auxiliary ligand for
the asymmetric synthesis of indinavir, a potent inhibitor of the
35
protease of human immunodeciency virus (HIV) and Detrol
LA (tolterodine tartrate), a muscarine receptor antagonist used
36a,b
for the treatment of urinary bladder disorder.
The indan-1-
one bearing carboxylate scaffold is also used as a peroxisome
proliferator activated receptor g (PPARg) agonist in the treat-
36c
ment of type-2 diabetes.
a
Therefore, a number of synthetic methods have been Entry
Catalyst
Loading (mol%)
Rxn. time
Yield (%)
reported that include intramolecular Friedel–Cras alkyl-
a
1
2
3
4
5
6
7
8
9
10
1
12
SbCl
SbCl
MgCl
ZrCl4
3
10
10
10
10
10
10
10
2
20–24 h
20–24 h
18–24 h
10–15 h
6 h
28
37
38,39
ation, Nazarov cyclization,
tandem Knoevenagel conden-
a
5
20
40
41
sation–cycloalkylation, Heck & Negishi coupling, Larock
a
2
18
42
43
a
annulations and ring-closing metathesis reactions with
10
b
44a
44b
45–51
SnBr
SnI
InCl
4
10
different Lewis acids such as SbF
5
,
AlCl
3
,
and TiCl
4
.
The
b
4
6 h
4–5 h
7
Friedel–Cras reactions were carried out at a high temperature
and in strong acidic conditions. Similarly, the enantioselective
indanones synthesis required a multi-step reaction and a high
a
3
90
b
SnCl
SnCl
4
30 min
15 min
2 min
1 min
2 min
45
65
98
b
4
5
32
b
catalyst loading for the 3-substituted indanone derivatives.
In continuation of our interest to develop a novel method-
SnCl4
InCl
TiCl
10
20
10
c
1
3
70 + 20
d
52
4
98
ology by using different Lewis acid catalysts. Herein, we report
an efficient deprotection method of THP and MOM ethers and a
sequential Friedel–Cras alkylation reaction in the stereo-
selective synthesis of functionalized 3-aryl-2-hydroxy-1-
a
b
Gave only the cyclization product. Gave both THP & MOM ether
deprotection and sequential cyclization. Gave side product of 3-(4-
c
d
chlorophenyl)-2-chloro-2,3-dihydro-indan-1-one (20%).
THP & MOM ether deprotection and sequential cyclization.
Gave both
indanone derivatives catalyzed by a highly efficient SnCl cata-
4
ꢀ
lyst at 0 C (Table 1). In comparison with other methods, our
protocol gave high yields (76–98%) with excellent regioselective
products (up to 99.9% ee) in a short reaction time (2–3 min).
THP and the MOM ethers in one-pot reaction within 2–3 min
under the same conditions (Table 1, entry 10 and 12). We also
4 4
used SnI and SnBr in 5, 10, and 20 mol% catalyst loadings
during the deprotection of the THP and the MOM ethers
Results and discussion
however they gave the products in 5–10% yield aer stirring for
ꢀ
2
–6 h at 0 C (Table 1).
Inspection of Table 1 reveals the catalytic efficiency of the
different metal halides. The metal halides (Table 1, entries 1–6)
exhibited poor to moderate catalytic activity. However, InCl
Table 1, entry 7) shows better activity at a 10 mol% catalyst
3
(
loading, which gave the cyclized products in a 90% yield without Table 2 Solvent effects on the yields in the deprotection of THP and
MOM ethers
deprotecting the THP and the MOM ethers. However, SnCl and
4
TiCl4 (Table 1, entry 10 and 12) were found to be the most
efficient catalysts at a 10 mol% catalyst loading and gave the
products in a 90–98% yield along with the deprotection of the
Entry
Mol%
Solvents
Yield (%)
a
1
2
3
4
5
6
7
8
2
5
5
10
5
10
5
Acetone
Acetone
DCM
40
a
45
b
80
b
DCM
98
c
CHCl
CHCl
THF
3
85
c
3
96
d
52
d
10
THF
60
a
b
c
Reaction time: 2 h. Reaction time: 3 min. Reaction time: 3 min.
Reaction time: 3 h.
d
Fig. 1 Bioactive indan-1-one derivatives.
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Table 3 Examples of the THP and MOM ether deprotection and sequential cyclization reactions
c
a
b
Entry
ROTHP/MOM
ROH
Time (min)
Yield (%)
Yield (%)
1
3
96
98
93
98
2
3
2
2
95
94
4
5
3
3
96
95
93
92
6
2
92
92
a
b
c
Yield (1–19) from R-OTHP ether deprotection. Yield (1–19) from R-OMOM ether deprotection. Entries 7–19, see ESI.
To optimize the reaction conditions, the catalyst (InCl3, 2,3-dihydroindan-1-one (20%), which was isolated and charac-
SnCl and TiCl ) loadings were carried out in 2, 5, 10 and 20 terized by GC-MS.
4
4
mol% (Table 1, entries 8–12). In CH Cl $SnCl at 2 and 5 mol%
Table 2 shows the solvent effects using acetone, chloroform,
loading the reaction proceeded slowly, whereas 20 mol% dichloromethane and tetrahydrofuran where CHCl and CH Cl
loading gave the side product as 3-(4-chlorophenyl)-2-chloro- were found to be the desired solvents (Table 2, entries 4 and 6).
2
2
4
3
2
2
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Table 4 Synthesis of 3-aryl-2-hydroxy-1-indanones from racemic the experimental section), the trans-chalcone epoxides 1a–1w
a,b,c
chalcone epoxides
were dissolved in CH Cl by stirring and SnCl or TiCl was
2
2
4
4
ꢀ
added in portion and stirred at 0 C for 2–3 min. Aer the usual
work up, the trans-3-aryl-2-hydroxy-2,3-dihydroindan-1-ones 2a–
2w were obtained in 76–98% yields (Table 4).
For example, in the synthesis of the racemic indanone 2b
(Table 4) the chiral HPLC purication gave peaks at 26.9 (50%)
and 35.4 (50%) min for the diastereomers (see Experimental
section). The assigned structures of the chalcone epoxides 1a–
1
w and the products 2a–2w were conrmed on the basis of their
1
13
spectral analysis (IR, H and C-NMR, and GC-MS/HRMS) and
were also compared with the reported data in the literature. The
trans-stereochemistry of the epoxides 1a–1w was conrmed by
the coupling constants of the a- & b-protons. For example,
(
4-chlorophenyl)-3-(4-bromophenyl)oxiran-2-yl-methanone (1i),
1
the H NMR (500 MHz) d (ppm): 4.07 (d, J ¼ 2.0 Hz, b-H, 1H),
4
.21 (d, J ¼ 2.0 Hz, a-H, 1H), in which the J-values (2.0 Hz)
indicated a trans-substituted epoxide. Similarly, the trans-
conguration of the 2-hydroxy-2,3-dihydro indan-1-ones 2a–2w
was conrmed by the coupling constants of the a- & b-protons.
For example, trans-3-(4-bromophenyl)-5-chloro-2-hydroxy-2,3-
1
dihydroindan-1-one (2i), the H NMR (500 MHz) d (ppm): 5.15
(
d, J ¼ 2.0 Hz, b-H, 1H), 5.31 (d, J ¼ 2.0 Hz, a-H, 1H), in which
42b
the J-values (2.0 Hz) indicated a trans-conguration. In the
case of electron donating (Table 4, entry 2j) and electron with-
drawing groups on the ring-Ar (Table 4, entries 2e, 2r and 2w)
2
ꢀ
the reaction at 0 C gave the decomposed products. Therefore,
the reactions were carried out by lowering the temperature
ꢀ
(
ꢁ20 C) to obtain the desired products.
Table 5 clearly shows that during the stereoselective
a
The epoxides and 2-hydroxyindan-1-ones are racemic compounds and synthesis of the indanones, rst we synthesized a diastereo-
are shown as a single enantiomeric derivative (trans-conguration).
b
ꢀ
isomeric excess of the trans (2R,3S)-chalcone epoxides (1x–1zb)
Reactions of 2e, 2j, 2r and 2w were carried out at ꢁ20 C and the
0
ꢀ
c
from the corresponding chalcone with a,a -diphenyl-L-prolinol
4
others at 0 C using 10 mol% of SnCl . Isolated yield of the racemic
2
-hydroxy indan-1-ones.
and TBHP in hexane which gave a good yield (58%) with 64–
99.9% enantiomeric excess. The epoxides were characterized by
comparing with the literature values and the enantiomeric
excess was determined by a chiral HPLC column and optical
rotation in chloroform (see the ESI†). The epoxide ring
Table 3 reveals that the THP and MOM removal followed by
the Friedel–Cras alkylation was observed for the chalcone
53
opening followed by intramolecular Friedel–Cras alkylation
epoxides which gave the corresponding indanone derivatives
was performed in the presence of TiCl
enantiomeric excess of the trans (2R,3S)-indanone derivatives
x–2zb (Table 5). The enantiomeric excess of the indanones was
4 4
or SnCl to obtain the
ꢀ
1
(
–6 in an excellent yield (90–98%) within 2–3 min at 0
C
Table 3, entries 1–6). The products were characterized on the
2
1
13
basis of their spectral analysis H-, C-NMR, GC-MS (see ESI†).
The one-pot deprotection of the phenolic THP and MOM
ethers followed by the Friedel–Cras alkylation reactions gave
again determined by a chiral HPLC column and optical rotation
in chloroform (see the Experimental section). In general, the
indanones were obtained in 90–98% yields with 64–99.9% ee
the indanones in a 90–98% yield at a 10 mol% catalyst loading
(Table 6, ESI†). It was observed that from the ring opening of the
ꢀ
(
TiCl
4
or SnCl
4
) within 2–3 min at 0 C. The presence of other
epoxides in the presence of the metal halides, the conguration
at the C-2 position was retained while the C-3 position was
changed due to a S 2-like mechanism to obtain regio- and
N
functional groups was fully tolerated under the optimized
conditions. However, for the alcoholic THP and MOM ethers, a
0 mol% catalyst loading gave only 10 and 25% yields respec-
tively (Table 3, entry 7). However, with the chalcones 12–19 only
THP and MOM removal was observed, but there was no intra-
molecular Friedel–Cras alkylation. The products were char-
acterized by comparing their physical and spectral data with
literature values (Table 3, entries 7–19, see ESI†).
2
stereoselective intramolecular Friedel–Cras alkylation. The
protons at the C-2 and C-3 positions are in a trans-orientation
which was conrmed by the coupling constants (J ¼ 2.0 Hz) in
1
the H NMR spectrum. Therefore, the absolute congurations at
C-2 and C-3 were conrmed as 2R and 3S respectively.
Tables 5 and 6† show that the assigned structures of the
enantiomeric excess trans-chalcone epoxides 1x–1zb and the
products 2x–2zb were conrmed on the basis of their spectral
Inspection of Table 4 reveals that in a racemic indanone
synthesis, following a simple experimental procedure (given in
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a,b,c
Table 5 Synthesis of enantioselective 3-aryl-2-hydroxy-1-indanones
b
a
Entry
1
Epoxide
Indanone
Yield (%)
ee (%) congn
98
90
72.2% (2R,3S)
75% (2R,3S)
2
3
4
92
95
64.8% (2R,3S)
>99.9% (2R,3S)
5
93
66.8% (2R,3S)
a
b
c
Enantiomeric excess (ee) was determined by a chiral HPLC column and was found to be equivalent to literature data. Isolated yields. Reactions
ꢀ
were carried out at 0 C for 2–3 min. The HPLC conditions and retention times of the racemic and enantiomeric excess of the indanone derivatives
are given in Table 6 (ESI).
1
13
analysis ( H- & C-NMR and chiral HPLC) and were also Similarly, all the other compounds 2y–2zb were conrmed on
compared with the reported data. For example, trans-3-(4- the basis of their analytical data.
chlorophenyl)-2-hydroxy-2,3-dihydroindan-1-one (2x) gave the
Scheme 1 shows that the stereoselectivity and high yields for
1
H NMR (500 MHz) d (ppm) at 5.36 (d, J ¼ 2.0 Hz, 1H, –CO–CH–) the 1-indanones under acidic conditions (TiCl or SnCl ) might
4
4
and 5.21 (d, J ¼ 2.0 Hz, –CH–Ar–, 1H), in which the J-values be due to the variable oxidation state and availability of the
1
3
indicated a trans-conguration. The C-NMR spectrum gave relatively low energy 5d-orbitals on tin. A proposed reaction
peaks at d 197.49 ppm for the characteristic carbonyl carbon, mechanism is shown in Scheme 1, where the ligation of SnCl
2.95 ppm for Ar–CH–CH, and 75.89 ppm for Ar–CH–CH–CO– with the MOM oxygen results in the removal of the methyl
4
6
ꢁ
of the indanone ring carbon. Since the diastereoselective (methylene) oxonium group followed by its reaction with Cl to
epoxide 1x gave the HPLC peaks at 54.7 min (13%) and 58.7 min generate the MOMCl. Similarly, the epoxide oxygen ligation
(
87%), the major peak correlated with the retention time of the might change the tetrahedron structure of SnCl
4
into a trigonal
54
reported literature.
Therefore, the conguration was bipyramide/octahedron structure. The geometry changes are
conrmed as 2R and 3S. We also took the diastereoselective enhanced by the steric hindrance which results in a faster
indanone 2x (Table 5) which gave peaks at 27.9 min (13.9%) and epoxide ring opening from the b-carbon due to the considerable
36.9 min (86.1%) (HPLC chromatogram in the ESI†). This electron decient character at the benzylic position. Therefore,
retention time matches those of the racemic indanone (2b). mostly the nucleophile attack takes place at the b-carbon of the
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General procedure for the deprotection of THP and MOM
ethers in alcohols and phenols followed by cyclization to
indanones
SnCl
4
or TiCl
4
(10 mol%) was added to a stirred solution of 1a–
ꢀ
1w & THP/MOM ethers (1 mmol) in CH
2
Cl
2
(5 mL) at 0 C. Aer
TLC monitoring, the reaction mixture was poured in a 10%
aqueous Na CO solution and was extracted with CH Cl . The
2
3
2
2
combined organic layer was washed with brine solution, dried
with anhyd. Na SO and concentrated in vacuo to give the cor-
2
4
responding alcohol or phenol, which was puried by silica gel
column chromatography with a hexane–EtOAc eluent to obtain
the products 2a–2w & 1 to 19 in excellent yields (80–98%).
trans-(2R,3S)-3-(4-Chlorophenyl)-2-hydroxy-2,3-dihydroindan-
1
-one (2x): light yellow solid; yield. 745 mg (98%); mp ¼ 188–190
ꢀ
ꢁ1
Scheme 1 Proposed mechanism for the deprotection of MOM ethers
C; IR vmax (KBr, cm ): 3408 (OH str), 2917 (aromatic C–H str),
4
followed by cyclization with SnCl .
1
689 (C]O str), 1589 (aromatic, C]C str), 1489, 1415, 1288,
1
1177, 1091, 1014, 929 and 701; H-NMR (CDCl , 500 MHz) d
3
(
7
ppm): 7.92 (d, J ¼ 7.5 Hz, 2H, H ), 7.69 (d, J ¼ 7.0 Hz, 1H, H ),
Ar
Ar
carbonyl group. Finally, the base hydrolysis produces SnCl
which is used in the next catalytic cycle.
4
.56 (t, J ¼ 7.0 Hz, 2H, HAr), 7.49 (d, J ¼ 7.5 Hz, 2H, HAr), 7.35 (d,
J ¼ 7.0 Hz, 1H, HAr), 5.36 (d, J ¼ 2.0 Hz, 1H, H2), 5.21 (d, J ¼ 2.0
1
3
Hz, 1H, H3), 4.13 (s, br, D
2 3
O exchangeable, 1H); C-NMR (CDCl ,
125 MHz) d (ppm): 197.4 (C]O), 136.6, 134.8, 134.4, 133.5, 129.4,
Conclusions
129.2, 128.7, 128.5, 75.9 (C2), 62.9 (C3); MS (EI, 70 eV): m/z (%) ¼
+
2
1
5
58(17) [M , C H ClO ], 242(28), 207(36), 179(43), 165(32),
15 11 2
In conclusion, we have developed a novel and highly efficient
catalytic protocol for the detetrahydropyranylation and deme-
thoxymethylation of phenolic ethers and the stereoselective
synthesis of trans-2-hydroxy-3-aryl-1-indanone derivatives by
sequential ring opening of the chalcone epoxides and intra-
35(57), 130(61), 105(100), 89(49), 77(61), 75(55) and
1(62); HRMS (ESI-TOF) calcd for C H ClO 258.0448,
1
5
11
2
found 258.0450; the absolute conguration was determined
by comparison with the optical rotation reported for the
25
[
a]
D
¼ ꢁ16.4 (c 1.0, CHCl
3
) and by chiral HPLC using a Chiralcel
molecular Friedel–Cras alkylation in the presence of SnCl
TiCl . This method has advantages such as (i) a mild protocol,
ii) an excellent yield (up to 98%) with high regio and stereo-
4
or
OD-H column.
4
trans-(2R,3S)-3-(4-Bromophenyl)-2-hydroxy-2,3-dihydroindan-
(
1
-one (2y): light yellow solid; yield. 546 mg (90%); mp. ¼ 183–185
selectivity (up to 99.9% ee), (iii) short reaction times (2–3 min)
and (iv) an easy work-up procedure. To the best of our knowl-
edge, SnCl and TiCl have not been studied in this capacity
ꢀ
ꢁ1
C; IR v
(KBr, cm ): 3434 (OH str), 2924 (aromatic C–H str),
max
1
1
7
670 (C]O str), 1588 (aromatic, C]C str), 1485, 1413, 1288,
1
4
4
3
177, 1071, 930, 703 and 545; H-NMR (CDCl , 500 MHz) d (ppm):
before and therefore represent a novel subject for investigation.
.91 (d, J ¼ 7.5 Hz, 2H, HAr), 7.57 (t, J ¼ 7.0 Hz, 1H, HAr), 7.50 (d,
J ¼ 7.0 Hz, 2H, HAr), 7.43 (d, J ¼ 7.0, 2.0 Hz, 2H, HAr), 7.24 (m, 1H,
H
Ar), 5.35 (d, J ¼ 2.0 Hz, 1H, H2), 5.19 (d, J ¼ 2.0 Hz, 1H, H3), 4.13
1
3
Experimental section
General methods
2 3
(s, br, D O exchangeable, 1H); C-NMR (CDCl , 125 MHz) d
(ppm): 197.3 (C]O), 136.6, 134.6, 134.2, 133.4, 129.3, 129.3,
1
3
8
28.6, 128.4, 76.0 (C2), 62.5 (C3); MS (EI, 70 eV): m/z (%) ¼
The organic solvents were dried by standard methods; the
reagents (chemicals) were purchased from commercial sources,
and were used without further purication. All the reactions
were monitored by TLC using precoated silica gel aluminum
plates. The visualization of the TLC plates was accomplished
with an UV lamp. Column chromatography was performed
using a silica gel 60–120 mesh size (RANKEM Limited) with
EtOAc–hexanes as the eluent. The melting points were recorded
on Pert apparatus and are uncorrected. All the products were
+
02(16) [M , C H BrO ], 196(55), 169(45), 139(73), 105(100),
1
5
11
2
9(47), 77(54), 63(49) and 51(66); HRMS (ESI-TOF) calcd for
11BrO 301.9942, found 301.9940; the absolute congura-
tion was determined by comparison with the optical rotation
C
15
H
2
25
D
reported for the [a]
using a Chiralcel OD-H column.
3
¼ ꢁ8.8 (c 1.2, CHCl ) and by chiral HPLC
trans-(2R,3S)-2-Hydroxy-3-phenyl-2,3-dihydrocyclo penta[b]
naphthalen-1-one (2z): light yellow solid; yield. 757 mg (92%);
ꢀ
ꢁ1
mp ¼ 114–116 C; IR n
(KBr, cm ): 3395 (OH str), 2951, 2848
max
1
13
characterized by NMR, IR and MS spectroscopy. H and
NMR spectra were recorded in deuterated chloroform (CDCl
C
(
aromatic C–H str), 1677 (C]O str), 1580 (aromatic, C]C str),
247, 1092, 842; H-NMR (CDCl , 500 MHz) d (ppm): 8.45 (m,
3
3
)
1
1
1
1
2
on a 500 MHz and 125 MHz spectrometer (Bruker), respectively.
The chemical shis were reported in parts per million (ppm, d)
downeld from tetramethylsilane. The proton coupling
patterns are described as singlet (s), doublet (d), triplet (t),
quartet (q), multiplet (m), and broad (br).
H, HAr), 7.99 (m, 2H, HAr), 7.85 (m, 1H, HAr), 7.65 (t, J ¼ 7.0 Hz,
H, HAr), 7.60 (m, 3H, HAr), 7.39–7.34 (m, 3H, HAr), 5.57 (d, J ¼
.0 Hz, 1H, H2), 5.32 (d, J ¼ 2.0 Hz, 1H, H3), 4.19 (s, br, D
2
O
13
exchange-able, 1H); C-NMR (CDCl , 125 MHz) d (ppm): 197.7
3
63100 | RSC Adv., 2015, 5, 63095–63103
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(
1
C]O), 138.2, 136.0, 132.4, 130.9, 130.5, 129.7, 129.3, 129.2,
3 (a) T. W. Green and P. G. M. Wuts, Organic Synthesis, John
Wiley, New York, 3rd edn, 1999, p. 306; (b) D. Caine and
H. J. Deutsch, J. Am. Chem. Soc., 1978, 100, 8031; (c)
M. Isobe, H. Iio, T. Kawai and T. Goto, J. Am. Chem. Soc.,
1978, 100, 1942.
28.8, 128.6, 128.0, 127.9, 127.3, 123.9, 76.2 (C2), 64.1 (C3); MS
+
(
EI, 70 eV): m/z (%) ¼ 274(12) [M c, C H O ], 256(15), 110(100);
1
9
14 2
HRMS (ESI-TOF) calcd for C H ClO 274.0994, found
1
9
14
2
2
74.0995; the absolute conguration was determined by
comparison with the optical rotation reported for the
4 (a) B. Tamami and K. Parvanak, Tetrahedron Lett., 2004, 45,
715; (b) V. V. Namboodiri and R. S. Varma, Tetrahedron
Lett., 2002, 43, 1143; (c) B. S. Babu and
K. Balasubramanian, Tetrahedron Lett., 1998, 39, 9287; (d)
P. N. Reddy, B. K. Sunil, P. S. Kumar, N. Y. Srinivasulu,
T. Reddy and B. Rajitha, Chem. Heterocycl. Compd., 2005,
41, 11.
5 B. Kumara, A. A. Mushtaq, D. Mukherjee, S. S. Chimnib,
S. C. Taneja and B. Kumar, Tetrahedron Lett., 2009, 50, 6236.
6 R. R. Diaz, C. R. Melgarejo, M. T. Plaza and I. I. Cubero, J.
Org. Chem., 1994, 59, 7928.
2
5
[
a]
D
¼ ꢁ3.5 (c 0.12, CHCl
3
) and by chiral HPLC using a Chir-
alcel AD-H column.
trans-(2R,3S)-3-(4-Chlorophenyl)-5-bromo-2-hydroxy-2,3-
dihydroindan-1-one (2za): light yellow solid; yield. 641 mg
ꢀ
ꢁ1
(
3
95%); mp ¼ 205–207 C; IR n
(KBr, cm ): 3422 (OH str),
max
087 (aromatic C–H str), 1678 (C]O str), 1583 (aromatic, C]C
1
str), 1404, 1278, 1169, 1091, 830, 752 (C–Br, str); H-NMR
CDCl , 500 MHz) d (ppm): 7.89 (m, 2H, HAr), 7.56–7.50 (m,
H, HAr), 7.41 (m, 2H, HAr), 5.31 (d, J ¼ 2.0 Hz, 1H, H2), 5.16, (d,
(
3
3
1
3
J ¼ 2.0 Hz, 1H, H3), 4.04 (s, br, D
CDCl , 125 MHz) d (ppm): 196.6 (C]O), 136.3, 134.9, 132.6,
32.3, 129.8, 129.4, 128.8, 75.9 (C2), 62.8 (C3); MS (EI, 70 eV): m/
2
O exchangeable, 1H); C-NMR
(
1
3
7 B. S. Babu and K. K. Balasubramanian, Tetrahedron Lett.,
1998, 39, 9287.
8 M. Narender, M. S. Reddy and K. R. Rao, Synthesis, 2004,
1741.
+
z (%) ¼ 336(30) [M c, C H ClBrO ], 185(79), 183(100), 125(49);
1
5
10
2
HRMS (ESI-TOF) calcd for C H BrClO 335.9553, found
1
5
10
2
3
35.9555; the absolute conguration was determined by
9 (a) C. Wiles, P. Watts and S. J. Haswell, Tetrahedron Lett.,
2005, 61, 5209; (b) C. Wiles, P. Watts and S. J. Haswell,
Tetrahedron Lett., 2006, 47, 261; (c) C. Wiles, P. Watts and
S. J. Haswell, Tetrahedron, 2007, 9, 966.
comparison with the optical rotation reported for the
2
5
[a]
D
3
¼ ꢁ10.1 (c 0.26, CHCl ) & by chiral HPLC using a Chiralcel
AD-H column.
trans-(2R,3S)-3-(4-Chlorophenyl)-2-hydroxy-5,6-dimethyl-2,3- 10 B. Karimi and J. Maleski, Tetrahedron Lett., 2002, 43, 5353.
dihydroinden-1-one (2zb): light yellow solid; yield. 533 mg 11 T. Mineno, Tetrahedron Lett., 2002, 43, 7975.
ꢀ
ꢁ1
(
2
93%); mp ¼ 116–118 C; IR n
(KBr, cm ): 3412 (OH str), 12 B. C. Ranu and M. Saha, J. Org. Chem., 1994, 59, 8269.
max
952, 2847 (aromatic C–H str), 1675 (C]O str), 1609 (aromatic, 13 G. G. Haraldsson and J. E. Baldwin, Tetrahedron, 1997, 53,
C]C str), 1225, 1091, 842, 762; H-NMR (CDCl
1
3
, 500 MHz) d
215.
(
2
ppm): 7.71 (m, 1H, HAr), 7.61 (d, J ¼ 7.5 Hz, 1H, HAr), 7.50 (m, 14 K. Tanemura, T. Haraguchi and T. Suzuki, Bull. Chem. Soc.
H, HAr), 7.33 (m, 1H, HAr), 7.28 (d, J ¼ 7.5 Hz, 1H, HAr), 5.25 (d,
Jpn., 1992, 65, 304.
J ¼ 2.0 Hz, 1H, H2), 5.14 (d, J ¼ 2.0 Hz, 1H, H3), 4.10 (s, br, D
2
O
15 H. M. S. Kumar, B. V. S. Reddy, E. J. Reddy and J. S. Yadav,
Chem. Lett., 1999, 28, 857.
1
3
3
exchangeable, 1H), 2.36 (s, 3H), 2.35 (s, 3H); C-NMR (CDCl ,
1
1
1
2
2
25 MHz) d (ppm): 197.1 (C]O), 144.4, 137.9, 136.9, 134.6, 16 J. S. Yadav, D. Srinivas and G. S. Reddy, Synth. Commun.,
31.1, 130.3, 129.7, 129.4, 128.7, 126.1, 75.6 (C2), 63.2 (C3), 20.2, 1998, 28, 1399.
9.9; MS (EI, 70 eV): m/z (%) ¼ 286 (10) [M c, C H ClO ], 17 A. T. B. Molnarand, Tetrahedron Lett., 1996, 37, 8597.
+
1
7
15
2
68(20), 122(100); HRMS (ESI-TOF) calcd for C17
H
15ClO
2
18 T. Akiyama, H. Shima and S. Ozaki, Synlett, 1992, 415.
86.0761, found 286.0763; the absolute conguration was 19 A. R. Srikrishna, J. A. Sattigeri and D. Vijaykumar, J. Org.
determined by comparison with the optical rotation reported
Chem., 1995, 60, 5961.
2
5
for the [a]
D
¼ ꢁ9.5 (c 0.57, CHCl
3
) and by chiral HPLC using a 20 K. K. Matthew and R. M. Waymouth, Organometallics, 2010,
29, 6051.
Chiralcel AD-H column.
2
2
2
2
1 S. Akai, R. Tanaka, H. Hoshi and K. I. Sato, J. Org. Chem.,
2013, 78, 8802.
Acknowledgements
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3 N. Ahmed, B. B. Venkata and H. Kumar, Synthesis, 2011,
Financial support and award of junior research fellowship by
the Department of Science and Technology (DST), New Delhi
and BRNS, BARC Mumbai, India is gratefully acknowledged. We
thank Prof. R. K. Peddinti, Chemistry IIT Roorkee for HPLC
assistance.
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