Diversity oriented approach to 9-aryl-substituted naphthoxepine derivatives via claisen rearrangement, ring-closing metathesis and suzuki-miyaura cross-coupling as key steps

Article abstract of DOI:10.3987/COM-12-S(N)89

A novel route to a variety of 9-aryl-substituted naphthoxepine derivatives is described starting with 6-bromo-2-naphthol via Claisen rearrangement (CR), ring-closing metathesis (RCM) and Suzuki-Miyaura (SM) cross-coupling as key steps.

Full text of DOI:10.3987/COM-12-S(N)89

HETEROCYCLES, Vol. 86, No. 2, 2012
1555
HETEROCYCLES, Vol. 86, No. 2, 2012, pp. 1555 - 1563. © 2012 The Japan Institute of Heterocyclic Chemistry
Received, 4th July, 2012, Accepted, 21st August, 2012, Published online, 4th September, 2012
DOI: 10.3987/COM-12-S(N)89
DIVERSITY ORIENTED APPROACH TO 9-ARYL-SUBSTITUTED
NAPHTHOXEPINE DERIVATIVES VIA CLAISEN REARRANGEMENT,
RING-CLOSING
METATHESIS
AND
SUZUKI–MIYAURA
CROSS-COUPLING AS KEY STEPS†
Sambasivarao Kotha,* Venu Srinivas, and Nimita G. Krishna
Department of Chemistry, Indian Institute of Technology-Bombay, Powai, India
Fax: 022-2572 7152; E-mail: srk@chem.iitb.ac.in
Abstract – A novel route to a variety of 9-aryl-substituted naphthoxepine
derivatives is described starting with 6-bromo-2-naphthol via Claisen
rearrangement (CR), ring-closing metathesis (RCM) and Suzuki−Miyaura (SM)
cross-coupling as key steps.
Oxepines are core structural units present in several of biologically active natural products such as
brevetoxin, gambierol, and ciguatoxin, which show potent antiviral and antifungal activities.1-4 A few
natural products 1-4 containing oxepine unit are depicted in Figure 1.2 For example, the construction of
(-)-clavizepine has been achieved via a benzoxepine intermediate.3
Me
OH
O
O
N
OH
O
O
O
O
Me
HO
Me
O
O
O
HO
eranthin (2)
ptaeroxylinol (1)
3
4
Figure 1. Natural products 1-4 comprising oxepine skeleton
Since the oxepine derivatives are useful building blocks, several efforts are directed towards their
synthesis and these methods4 include: (i) base-catalyzed cyclization of allenyl sulfoxides/sulfones, (ii)
_____________________________________________________________________________________
†This paper is dedicated to Prof. Dr. Ei-ichi Negishi on the occasion of his 77th birthday

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HETEROCYCLES, Vol. 86, No. 2, 2012
carbocyclization by rhodium-catalysis, (iii) intramolecular acyl radical cyclization, (iv) Lewis-acid
catalyzed intramolecular cyclization. However, these routes require the usage of expensive catalyst and
require high temperature affording the products in low yields.
In view of some of the limitations towards the synthesis of naphthoxepine derivatives and also our interest
in these molecules, we have conceived a strategy based on Claisen rearrangement (CR), ring-closing
metathesis (RCM) and SuzukiMiyaura cross-coupling (SM) as key steps. Since CR, olefin metathesis and
SM coupling are considered catalytic processes, utilization of these strategies in a synthetic sequence
increases the ‘green content’ of the overall synthesis.
During the past two decades, olefin metathesis has drawn considerable attention because of a wide range of
transformations that are possible with commercially available and easy to handle catalysts. A variety of
retrosynthetic paths are opened to carbocycles, polycyclics and macrocycles by incorporating the RCM
reaction sequence.5-6 Based on the above considerations, we have designed a novel approach to oxepine
derivative 6 by employing the inexpensive β-naphthol derivative 5 as starting material. In this regard
O-allylation, microwave (MW) assisted CR and finally the RCM as key steps (Scheme 1) can generate the
known building block 6.7 The SM cross-coupling can be performed at different stages of the synthetic
sequence.
i
O-allylation
OH
ii CR
O
iii O-allylation
iv RCM
Br
Br
5
6
Scheme 1. Synthesis of naphthoxepine 6
Our strategy to oxepine derivative 6 starts with 6-bromo-2-naphthol (5) as the starting precursor. To this
end, 6-bromo-2-naphthol (5) was O-allylated by using allyl bromide/K2CO3 in acetone to yield the
desired product 7 (98%). Later, the MW-assisted CR of allyl derivative 7 followed by O-allylation gave
the diallyl derivative 8 (93%).7b Since Grubbs catalyst 9 is expensive, our initial intention was to perform
the metathesis step at the end of the synthetic sequence. In this regard, diallyl compound 8 was treated
with phenylboronic acid under Pd(0) conditions. Unfortunately, a mixture of compounds was formed. So,
it was decided to prepare the RCM product first and then attempt the SM coupling8 as a last step. To
prepare the 9-bromo-naphthoxepine (6) required for the SM coupling reaction, the diallylated compound
8 was subjected to RCM in the presence of Grubbs first generation catalyst (9, 5 mol%) in
dichloromethane (Scheme 2) to generate the compound 6 in 96% yield.7b

HETEROCYCLES, Vol. 86, No. 2, 2012
1557
OH
O
O
O
(ii-iii)
iv
(i)
Br
Br
Br
Br
5
7
8
6
Scheme 2. Synthetic approach towards the RCM product 6. Reaction conditions: (i) allyl bromide,
K2CO3, acetone, rt, 14 h, 98%; (ii) silica gel supported MWI (800W) assisted CR, 8 min, 88%; (iii) allyl
bromide, K2CO3, acetone, rt, 16 h, 93%; (iv) (Cy3P)2Cl2Ru = CHPh [9, 5.0 mol%], DCM, rt, 4 h, 96%.
The bromo compound 6 was treated with phenylboronic acid in the presence of Pd(PPh3)4 (5.0 mol%),
Na2CO3 (2.0 equiv) in toluene/THF/water (1:1:1) as the solvent mixture to furnish the cross-coupling
product 10a in an excellent yield (90%, Scheme 3).8b Later, the substrate scope has been expanded by
employing various arylboronic acids under similar conditions to generate the desired 9-arylnaphthoxepine
derivatives 10b-i in moderate to excellent yield.
Ar-B(OH)2
Pd(PPh3)4 (5 mol%)
Na2CO3 (2 mol equiv)
O
O
toluene/THF/H2O (1:1:1)
100 oC, 20-30 h
Ar
Br
10a-i
6
62-93 %
Scheme 3. Synthesis of diverse SM coupling products 10a-i
1
All these final products were characterized by H NMR/13C NMR spectral data. Among these products
obtained, phenyl- and 3-methylphenyl-substituted derivatives 10a-b were formed in excellent yield
(86-90%) while the 4-formylphenyl (electron withdrawing) and 4-bromophenyl-based derivatives 10c-d
were accomplished in slightly lower yield (75-80%) compared to 10a-b (Figure 2). In addition,
3-thiophene-based SM cross-coupling product 10e was also obtained in a moderate yield (62%). However,
heteroaromatic cross-coupling compounds 10h-i were obtained in excellent yields. Due to the presence of
different functional groups, these coupling products can be used for further synthetic manipulation to
generate biologically useful molecules.
In conclusion, we have disclosed a simple and mild synthetic strategy to novel 9-arylnaphthoxepine
adducts via CR, RCM and SM reaction as key steps. These products are obtained in very good yields. The
scope of this reaction can be further extended because some of these SM-cross coupling products contain
additional functionalities for further synthetic manipulation.

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HETEROCYCLES, Vol. 86, No. 2, 2012
O
O
O
O
Me
10a (90)
10d (75)
10b (86)
10c (80)
OHC
MeO
O
O
10e (62)
10f
(93)
Br
S
O
O
O
N
H
10g (84)
10h
(84)
10i
(91)
NC
S
Figure 2. List of SM cross-coupling products (10a-i) obtained from 6. Yields are given in the
parentheses.
EXPERIMENTAL
Melting points were recorded on Labhosp or Veego melting point apparatus. Infrared (IR) spectra were
recorded on Nicolet Impact-400 FT IR spectrometer in KBr/CHCl3/CCl4. 1H NMR (400 MHz), 13C NMR
(100 MHz or 75 MHz) spectral data were determined at r.t. on AV 400 (Bruker) or Varian in CDCl3
solution. Coupling constants (J values) are given in Hertz (Hz). The high-resolution mass measurements
were carried out using Micromass Q-Tof spectrometer. Analytical thin layer chromatography (TLC) was
performed on (10 × 5 cm) glass plates coated with Acme’s silica gel G or GF 254 (containing 13%
calcium sulfate as a binder). Column chromatography was performed using Acme’s silica gel (100-200
mesh) using double spray bellows for application of pressure and the column is eluted with ethyl
acetate-petroleum ether mixture. Solvents used in this study were dried over appropriate drying agents and
distilled prior to use. Compound 6 was prepared according to the reported procedure.7b
Suzuki−Miyaura cross-coupling reaction: General procedure
To a solution of bromo derivative 6 (1.0 equiv.) in THF/toluene/water (1:1:1) was added Na2CO3 (3-4
equiv.) and arylboronic acid (2.0 equiv.). The reaction mixture was degassed with nitrogen for 20 minutes.
The catalyst Pd(PPh3)4 (5 mol%) was subsequently added and the reaction mixture was heated at 100 °C
(oil bath temperature). After completion of the reaction (12-30 h, TLC monitoring), the solvent was
removed under reduced pressure and the residue was diluted with EtOAc. The organic layer was washed
with water (10 mL), brine (10 mL) and dried over Na2SO4. The solvent was evaporated and the crude

HETEROCYCLES, Vol. 86, No. 2, 2012
1559
product was purified by silica gel column chromatography (EtOAc/petroleum ether).
9-Phenyl-1,4-dihydronaphtho[2,1-b]oxepine (10a): This compound was prepared according to the
general procedure by treating the compound 6 (50 mg, 0.18 mmol) in THF-toluene (1:1) mixture (12 mL),
aq. Na2CO3 (77 mg, 0.73 mmol), with phenylboronic acid (44 mg, 0.36 mmol) and Pd(PPh3)4 (12 mg, 0.01
mmol) (heating at 100 °C for 20 h). The crude product was purified by silica gel column chromatography
(2% EtOAc-petroleum ether) to give the desired coupling product 10a (44.2 mg, 90%) as a colorless solid;
1
Rf = 0.45 (silica gel, 5% EtOAc-petroleum ether); Mp 143-144 °C; H NMR (400 MHz, CDCl3):  =
3.26-3.32 (m, 1H), 3.67-3.73 (m, 1H), 5.27 (d, J = 10.3 Hz, 1H), 5.39-5.48 (m, 2H), 6.08-6.16 (m, 1H), 7.15
(d, J = 8.8 Hz, 1H), 7.34-7.39 (m, 1H), 7.45-7.53 (m, 2H), 7.63-7.79 (m, 5H), 8.01 (d, J = 1.3 Hz, 1H); 13C
NMR (100 MHz, CDCl3):  = 34.9, 84.5, 112.7, 117.1, 118.2, 123.4, 124.3, 126.6, 126.9, 127.2, 127.4,
~
127.5, 129.0, 129.6, 129.7, 130.1, 135.8, 137.6, 141.4, 157.3; IR (KBr): v = 3020, 1602, 1519, 1473, 1421,
1216, 1017 cm-1; HRMS (Q-Tof): m/z calcd for C20H17O [M+H]+ 273.1279; found: 273.1277.
9-m-Tolyl-1,4-dihydronaphtho[2,1-b]oxepine (10b): This compound was prepared according to the
general procedure by treating the compound 6 (50 mg, 0.18 mmol) in THF-toluene (1:1) mixture (10 mL),
aq. Na2CO3 (77 mg, 0.73 mmol), with 3-methylphenylboronic acid (49 mg, 0.36 mmol) and Pd(PPh3)4
(11 mg, 0.01 mmol) (heating at 100 °C for 18 h). Purification of the crude material by silica gel column
chromatography (1% EtOAc-petroleum ether) gave the desired coupling product 10b (45 mg, 86%) as a
1
gummy solid; Rf = 0.28 (silica gel, petroleum ether); H NMR (400 MHz, CDCl3):  = 2.46 (s, 3H),
3.27-3.33 (m, 1H), 3.67-3.73 (m, 1H), 5.28 (d, J = 10.4 Hz, 1H), 5.39-5.49 (m, 2H), 6.09-6.18 (m, 1H),
7.17 (t, J = 8.8 Hz, 2H), 7.36-7.39 (m, 1H), 7.49-7.54 (m, 2H), 7.63 (d, J = 8.6 Hz, 1H), 7.73-7.79 (m,
13
2H), 8.02 (d, J = 1.6 Hz, 1H); C NMR (100 MHz, CDCl3):  = 21.8, 34.9, 84.5, 112.6, 117.1, 118.2,
123.3, 124.5, 126.6, 126.8, 127.9, 128.1, 128.9, 129.6, 129.7, 130.1, 135.9, 137.6, 138.6, 141.4, 157.2; IR
-1
~
(neat): v = 3053, 2986, 2926, 2854, 1631, 1603, 1491, 1421, 1265, 1096 cm ; HRMS (Q-Tof): m/z
calcd for C21H19O [M+H]+ 287.1436; found: 287.1446.
4-(1,4-Dihydronaphtho[2,1-b]oxepin-9-yl)benzaldehyde (10c): This compound was prepared according
to the general procedure by treating the compound 6 (30 mg, 0.11 mmol) in THF-toluene-water (1:1:1),
Na2CO3 (46 mg, 0.44 mmol) with 4-formylphenylboronic acid (32.7 mg, 0.22 mmol) and Pd(PPh3)4 (12
mg, 0.01 mmol) heating at 100 °C for 18 h. Purification of the crude material by silica gel column
chromatography (1.5% EtOAc-petroleum ether) gave the desired coupling product 10c (26 mg, 80%) as a
colorless solid; Rf = 0.45 (silica gel, 10% EtOAc-petroleum ether); Mp 122-124 °C; 1H NMR (400 MHz,
CDCl3):  = 3.31-3.33 (m, 1H), 3.72-3.74 (m, 1H), 5.28 (d, J = 10.2 Hz, 1H), 5.31-5.48 (m, 2H),
6.08-6.17 (m, 1H), 7.19 (d, J = 8.8 Hz, 1H), 7.68 (d, J = 8.8, 1H), 7.78 (dt, J1 = 8.4, J2 = 2.0 Hz, 2H), 7.87
(d, J = 8.4 Hz, 2H), 7.99 (d, J = 8.0 Hz, 2H), 8.09 (s, 1H), 10.10 (s, 1H); 13C NMR (100 MHz, CDCl3): 

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HETEROCYCLES, Vol. 86, No. 2, 2012
= 34.8, 84.6, 113.1, 117.2, 118.4, 123.8, 126.1, 127.7, 127.8, 129.5, 129.9, 130.6, 130.7, 134.1, 135.1,
-1
~
137.5, 147.4, 157.9, 192.1; IR (KBr): v = 3020, 1698, 1602, 1522, 1424, 1216 cm ; HRMS (Q-Tof):
m/z calcd for C21H17O2 [M+H]+ 301.1229; found: 301.1219.
9-(4-Bromophenyl)-(1,4-dihydronaphtho[2,1-b]oxepine (10d): This compound was prepared according
to the general procedure by treating the compound 6 (100 mg, 0.36 mmol) in THF-toluene-water (1:1:1)
mixture (20 mL), Na2CO3 (154 mg, 1.5 mmol) with 4-bromophenylboronic acid (110 mg, 0.55 mmol)
and Pd(PPh3)4 (21 mg, 0.02 mmol) heating at 100 °C for 24 h. Purification of the crude material by silica
gel column chromatography (0.2% EtOAc-petroleum ether) gave the desired coupling product 10d (95
mg, 75%) as a colorless solid; Rf = 0.22 (silica gel, petroleum ether); Mp 118-120 °C; 1H NMR (400 MHz,
CDCl3):  = 3.26-3.32 (m, 1H), 3.67-3.73 (m, 1H), 5.28 (d, J = 10.4 Hz, 1H), 5.39-5.48 (m, 2H),
6.07-6.16 (m, 1H), 7.16 (d, J = 8.8 Hz, 1H), 7.47-7.75 (m, 7H), 7.98 (d, J = 1.6 Hz, 1H); 13C NMR (100
MHz, CDCl3):  = 34.8, 84.4, 112.8, 117.0, 118.2, 121.3, 123.5, 126.0, 126.7, 128.8, 129.6, 130.2, 132.0,
-1
~
134.5, 137.5, 140.2, 157.4; IR (KBr): v = 3055, 2978, 2296, 1626, 1497, 1265, 1074 cm ; HRMS
(Q-Tof): m/z calcd for C20H16OBr [M+H]+ 351.0385; found: 351.0380.
9-(Thiophen-3-yl)-1,4-dihydronaphtho[2,1-b]oxepine (10e): This compound was prepared according to
the general procedure by treating the compound 6 (50 mg, 0.18 mmol) in THF-toluene-water (1:1:1)
mixture (10 mL), Na2CO3 (77 mg, 0.73 mmol) with 3-thienylboronic acid (46.5 mg, 0.36 mmol) and
Pd(PPh3)4 (12 mg, 0.01 mmol) heating at 100 °C for 22 h. Purification of the crude material by silica gel
column chromatography (1.5% EtOAc-petroleum ether) gave the desired coupling product 10e (31 mg,
62%) as a white solid; Rf = 0.49 (silica gel, 5% EtOAc-petroleum ether); Mp 138-140 °C; 1H NMR (400
MHz, CDCl3):  = 3.26-3.32 (m, 1H), 3.66-3.72 (m, 1H), 5.30 (d, J = 10.4 Hz, 1H), 5.31-5.49 (m, 2H),
6.10-6.18 (m, 1H), 7.16 (d, J = 8.7 Hz, 1H), 7.43-7.7.45 (m, 1H), 7.51-7.54 (m, 2H), 7.6 (d, J = 8.6 Hz,
13
1H), 7.74 (d, J = 1.8 Hz, 1H), 7.76 (d, J = 1.8 Hz, 1H), 8.02 (d, J = 1.6 Hz, 1H); C NMR (100 MHz,
CDCl3):  = 34.7, 84.3, 112.5, 116.9, 118.2, 119.9, 123.3, 125.7, 125.9, 126.3, 126.4, 129.3, 129.5, 129.9,
-1
~
130.4, 137.4, 142.4, 157.1; IR (KBr): v = 3054, 2986, 2685, 1604, 1421, 1266, 1155 cm ; HRMS
(Q-Tof): m/z calcd for C18H15OS [M+H]+ 279.0844; found: 279.0856.
9-(4-Methoxyphenyl-1,4-dihydronaphtho[2,1-b]oxepine (10f): This product was obtained according to
the general procedure by treating the compound 6 (65 mg, 0.24 mmol) in THF-toluene-water (1:1:1)
mixture (12 mL), Na2CO3 (100 mg, 0.95 mmol) with 4-methoxyphenylboronic acid (72 mg, 0.5 mmol)
and Pd(PPh3)4 (14 mg, 0.01 mmol) heating at 100 °C for 26 h. Purification of the crude material by silica
gel column chromatography (2% EtOAc-petroleum ether) gave the desired coupling product 10f (67 mg,
1
93%) as a colorless solid; Rf = 0.45 (silica gel, 5% EtOAc-petroleum ether); Mp 150-152 °C; H NMR
(400 MHz, CDCl3):  = 3.28 (dd, J = 15.3 Hz, J = 7.6 Hz, 1H), 3.69 (dd, J = 15.3 Hz, J = 10.4 Hz, 1H),

HETEROCYCLES, Vol. 86, No. 2, 2012
1561
3.85 (s, 3H), 5.27 (d, J = 10.4 Hz, 1H), 5.38-5.47 (m, 2H); 6.08-6.16 (m, 1H), 6.96 (d, J = 8.4 Hz, 1H),
7.02 (d, J = 9.2 Hz, 1H), 7.14 (d, J = 8.8 Hz, 1H), 7.48 (d, J = 8.8 Hz, 1H), 7.62-7.64 (m, 2H), 7.69-7.73
(m, 2H), 7.96 (d, J = 1.8 Hz, 1H); 13C NMR (100 MHz, CDCl3):  = 34.9, 55.5, 84.4, 112.6, 114.3, 114.5,
117.0, 118.2, 123.4, 126.1, 126.5, 127.9, 128.4, 129.4, 129.8, 133.7, 133.9, 135.5, 137.7, 157.1, 158.9; IR
-1
~
(KBr): v = 3054, 2986, 2685, 2305, 1607, 1551, 1421, 1264, 1156 cm ; HRMS (Q-Tof): m/z calcd for
C21H19O2 [M+H]+ 303.1385; found: 303.1390.
4-(1,4-Dihydronaphtho[2,1-b]oxepin-9-yl)benzonitrile (10g): This compound was prepared according
to the general procedure by treating the compound 6 (35 mg, 0.13 mmol), Na2CO3 (55 mg, 0.51 mmol)
with 4-cyanophenylboronic acid (37.4 mg, 0.25 mmol), in THF-toluene-water (1:1:1) mixture (12 mL)
and Pd(PPh3)4 (14.7 mg, 0.013 mmol). The reaction mixture was heated at 100 °C for 24 h. The crude
product was purified by silica gel column chromatography (2.5% EtOAc-petroleum ether) to give the
desired coupling product 10g (31 mg, 84%) as a colorless solid; Rf = 0.22 (silica gel, 5%
EtOAc-petroleum ether); Mp 147-150 °C; 1H NMR (400 MHz, CDCl3):  = 3.27-3.33 (m, 1H), 3.68-3.75
(m, 1H), 5.29 (d, J = 10.4 Hz, 1H), 5.44-5.49 (m, 2H), 6.08-6.17 (m, 1H), 7.19 (d, J = 8.8 Hz, 1H),
7.66-7.80 (m, 7H), 8.03 (s, 1H); 13C NMR (75 MHz, CDCl3):  = 34.8, 84.6, 110.7, 113.2, 117.2, 118.4,
~
119.2, 123.9, 125.8, 127.6, 127.8, 129.5, 129.9, 130.8, 132.8, 133.6, 137.4, 145.9, 158.0; IR (KBr): v =
3054, 2986, 2923, 2227, 1603, 1503, 1421, 1265 cm-1; HRMS (Q-Tof): m/z calcd for C21H16NO [M+H]+
298.1232; found: 298.1225.
9-(Benzo[b]thiophen-3-yl)-1,4-dihydronaphtho[2,1-b]oxepine (10h): This compound was prepared
according to the general procedure by treating the compound 6 (50 mg, 0.18 mmol), Na2CO3 (77 mg, 0.73
mmol) with benzothiophene-3-boronic acid (65 mg, 0.36 mmol) and Pd(PPh3)4 (12 mg, 0.01 mmol) in
THF-toluene-water (1:1:1) mixture (10 mL). It was heated at 100 °C for 25 h. Purification of the crude
material by silica gel column chromatography (1% EtOAc-petroleum ether) gave the desired coupling
product 10h (50 mg, 84%) as a colorless solid; Rf = 0.1 (silica gel, petroleum ether); Mp 153-158 °C; 1H
NMR (400 MHz, CDCl3):  = 3.27 (dd, J = 15.3 Hz, J = 7.6 Hz, 1H), 3.68 (d, J = 15.3 Hz, J = 9.6 Hz,
1H), 5.28 (dt, J1 = 10.2 Hz, J2 = 1.2 Hz, 1H), 5.39-5.47 (m, 2H), 6.07-6.16 (m, 1H), 7.15 (d, J = 8.7 Hz,
13
1H), 7.28-7.32 (m, 2H), 7.58-7.78 (m, 4H), 7.82-7.85 (m, 2H), 8.11 (d, J = 1.8 Hz, 1H); C NMR (100
MHz, CDCl3):  = 34.9, 84.6, 113.0, 117.2, 118.6, 119.3, 122.4, 123.5, 123.6, 124.4, 124.7, 125.4, 126.5,
~
129.0, 129.5, 129.7, 130.7, 137.5, 139.5, 141.0, 144.7, 157.7; IR (KBr): v = 3054, 2986, 1421, 1265
cm-1; HRMS (Q-Tof): m/z calcd for C22H17OS [M+H]+ 329.1000; found: 329.1004.
5-(1,4-Dihydronaphtho[2,1-b]oxepin-9-yl)-1H-indole (10i): This compound was prepared according to
the general procedure by treating the compound 6 (35 mg, 0.13 mmol) with indole-5-boronic acid (41 mg,
0.25 mmol), Na2CO3 (54 mg, 0.5 mmol) and Pd(PPh3)4 (12 mg, 0.01 mmol) in THF-toluene-water (1:1:1)

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HETEROCYCLES, Vol. 86, No. 2, 2012
mixture (8 mL). The reaction mixture was heated at 100 °C for 30 h. Purification of the crude material by
silica gel column chromatography (2% EtOAc-petroleum ether) gave the desired coupling product 10i
(36.2 mg, 91%) as a colorless solid; Rf = 0.38 (silica gel, 5% EtOAc-petroleum ether); Mp 160-163 °C;
1H NMR (400 MHz, CDCl3):  = 3.26-3.34 (m, 1H), 3.67-3.73 (m, 1H), 5.27 (dt, J1 = 10.4 Hz, J2 = 1.1
Hz, 1H), 5.38-5.47 (m, 2H), 6.08-6.17 (m, 1H), 6.62-6.64 (m, 1H), 7.14 (d, J = 8.8 Hz, 1H), 7.23-7.25 (m,
1H), 7.45-7.48 (m, 1H), 7.55-7.57 (m, 1H), 7.64 (dd, J1= J2 = 8.5 Hz, 1H), 7.74 (d, J = 8.6 Hz, 1H), 7.82
13
(dd, J1= 8.6 Hz, J2 = 1.9 Hz, 1H), 7.95-7.96 (m, 1H), 8.05 (d, J = 1.8 Hz, 1H), 8.19 (br, 1H); C NMR
(100 MHz, CDCl3):  = 34.9, 84.4, 103.2, 111.5, 112.5, 117.0, 118.1, 119.4, 122.2, 123.2, 125.0, 126.6,
~
127.3, 128.7, 129.4, 129.7, 129.9, 133.6, 135.4, 137.2, 137.7, 156.9; IR (KBr): v = 3475, 3053, 2986,
2253, 1605, 1481, 1422, 1263, 1093 cm-1; HRMS (Q-Tof): m/z calcd for C22H18NO [M+H]+ 312.1388;
found: 312.1401.
ACKNOWLEDGEMENTS
We thank Department of Science and Technology (DST), New Delhi, and Industrial Research and
Consultancy Centre (IRCC), IIT-Bombay for financial support. We also thank Sophisticated Analytical
Instrument Facility (SAIF), IIT-Bombay for recording spectral data. S. K. thanks Department of Science
and Technology for the award of a J. C. Bose fellowship. N. G. K. thanks Department of Chemistry,
IIT-Bombay for awarding the research fellowship.
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