Diversity-oriented synthesis of biaryl derivatives using cross-enyne metathesis, diels-alder reaction, and suzuki-miyaura cross-coupling as key steps

Article abstract of DOI:10.1055/s-0030-1260315

Biaryl derivatives have been prepared by utilizing cross-enyne metathesis, Diels-Alder reaction followed by aromatization. These biaryl derivatives are further functionalized via Suzuki-Miyaura cross-coupling reaction to generate functionalized terphenyl derivatives. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0030-1260315

LETTER
2329
Diversity-Oriented Synthesis of Biaryl Derivatives Using Cross-Enyne
Metathesis, Diels–Alder Reaction, and Suzuki–Miyaura Cross-Coupling
as Key Steps
D
iversity-Orie
a
nted
S
ynth
m
esis of Biaryl
D
eriv
b
Department of Chemistry, Indian Institute of Technology-Bombay, Powai, Mumbai 400076, India
Fax +91(22)25767152; E-mail: srk@chem.iitb.ac.in
Received 26 May 2011
Dedicated to the memory of Prof. K. D. Deodher
sypol).6 Binaphthyl polyphenyls are used as male
antifertility agents and polycholorobiphenyls (PCB) are
recognized as environmental polluants.7
Abstract: Biaryl derivatives have been prepared by utilizing cross-
enyne metathesis, Diels–Alder reaction followed by aromatization.
These biaryl derivatives are further functionalized via Suzuki–
Miyaura cross-coupling reaction to generate functionalized terphe-
nyl derivatives.
Transition-metal-catalyzed cross-coupling8 of aryl ha-
lides with aryl organometallic species has been used for
the development of synthetic methods allowing C–C cou-
pling between two aryl groups. While the metathesis9,10
protocol (Figure 2) and Diels–Alder chemistry is often
used to create new C–C bonds, only a few reports describe
biaryl preparation involving the Diels–Alder reaction as a
key step.
Key Words: biaryl derivatives, cross-enyne metathesis, Suzuki–
Miyaura cross-coupling, diversity-oriented synthesis
The biaryl unit is a core structural element present in nat-
urally occurring products such as alkaloids, lignans, ter-
penes, and flavonoids.1 In addition, the biaryl unit is found
in several medicinally important compounds (e.g., antibi-
otics, anti-inflammatories, antihypertensives, anticancer,
and antifungal agents).2 For example, losartan3 is one of
the most prescribed drugs for antihypertension. Several
important biaryl derivatives are shown in Figure 1.4 The
biaryl motif may also be a component of agrochemicals,
liquid crystals, and molecular switches.5 Several structur-
al components of biaryls are natural pigments (e.g., gos-
Mes-N
Cl
N-Mes
Ph
PCy3
Ru
Ph
H
Cl
Cl
Ru
H
Cl
PCy3
PCy3
Grubbs I (8)
Grubbs II (9)
Figure 2 Various Grubbs catalysts used in cross-enyne metathesis
OH
O
OH
O
Cl
O
OH
N
N
N
Me
O
N
NH
O
MeO
MeO
NH
Cl
MeO
OMe
O
N
O
n-Bu
Me
OMe
Cl
N
O
boscalide (2)
(–)-steganone (1)
losartan (3)
knipholone (4)
Me
Me
N
OMe
O
N
N
OMe
NH
O
N
n-Pr
N
HO
O
N
N
Me
NH
Me
micardis (5)
conivaptan (7)
buflavine (6)
Figure 1 Various biaryl-containg molecules
SYNLETT 2011, No. 16, pp 2329–2334
x
x
.x
x
.2
0
1
1
Advanced online publication: 13.09.2011
DOI: 10.1055/s-0030-1260315; Art ID: D16111ST
© Georg Thieme Verlag Stuttgart · New York

2330
S. Kotha, V. Seema
LETTER
CO2Me
CO2Me
X
COMe
X
Y
Y
X
X
Y
Y
CO2Me
CO2Me
X
Y
X
Y
Figure 3 Retrosynthetic approaches towards biaryl derivatives
Herein, we report a new strategy for the synthesis of biaryl
derivatives involving cross-enyne metathesis and Diels–
Alder reaction11,12 as key steps. The first step in the strat-
egy involves cross-enyne metathesis with 1,5-hexadiene
to generate homoallyl diene derivatives, and ethylene-me-
diated cross-metathesis to generate 1,3-diene derivatives
(Figure 3).13 These dienes are subjected to Diels–Alder
reaction with a dienophile such as dimethyl acetylenedi-
carboxylate (DMAD)14 followed by aromatization to gen-
erate highly substituted biaryl systems. Subsequently,
Suzuki–Miyaura cross-coupling15 with these biaryl sys-
tems can generate highly functionalized terphenyl deriva-
tives.
CO2Me
CO2Me
CO2Me
CO2Me
(ii)
+
X
X
Y
Y
(iii)
(i) a, b
CO2Me
CO2Me
X
Y
Various commercially available functionalized acetophe-
nones 10 were converted into aryl acetylene derivatives
12 by using known methodology (Scheme 1).16
X
X = OMe, Y = OMe
X = OMe, Y = H
X = I, Y = H
Y
X = Br, Y = H
X = Cl, Y = H
Cl
Scheme 2 Reagents and conditions: (i) (a) Grubbs II, 1,5-hexadie-
ne, toluene 90 °C, 24 h; (b) Grubbs I, 1,5-hexadiene, CH2Cl2, 12 h; (ii)
toluene, 90 °C, 24 h; (iii) DDQ, toluene, reflux, 36 h.
COMe
(ii)
(i)
CHO
X
X
X
11
10
12
material was not completely consumed. The reaction was
subsequently carried out using Grubbs first-generation
catalyst 8 in CH2Cl2 at room temperature under nitrogen,
and it was found that the reaction rate was much faster and
that the reaction proceeded to completion within 12 hours.
Again, an inseparable mixture of cis/trans isomers of di-
ene 14 was obtained in good yield. Since the dienes are
used to generate aromatic products by a Diels–Alder reac-
tion and aromatization sequence, the geometry of the dou-
ble bond present in 14 is of no consequence in the present
study.
Scheme 1 Preparation of various phenyl acetylene derivatives.
Reagents and conditions: (i) DMF, POCl3; (ii) NaOH, 1,4-dioxane.
Initially, the cross-enyne metathesis was performed start-
ing with 3,4-di-methoxyphenylacetylene 13 and 1,5-hexa-
diene as a cross-coupling partners in the presence of
Grubbs first-generation catalyst 8 in CH2Cl2 (Scheme 2).
After considerable experimentation, we found that the
highest yield of the cross-metathesis product was obtained
at 90 °C in toluene. In toluene at reflux, two products were
observed: the expected cross-enyne metathesis product 14
and another benzoanulated product 15. The cross-enyne
product 14 was converted into the 3,4-dimethoxybiaryl
system 15 (Scheme 3) by an intramolecular metathesis
and aromatization sequence.
(i)
+
MeO
During the cross-enyne metathesis in toluene at 90 °C the
products were obtained as an inseparable mixture of cis/
trans isomers.17 When the halogenated acetylene deriva-
tives were subjected to cross-enyne metathesis with 1,5-
hexadiene in toluene at 90 °C and under reflux, starting
MeO
MeO
OMe
OMe
13
OMe
14 46%
15 27%
Scheme 3 Reagents and conditions: (i) 1,5-hexadiene, Grubbs II,
toluene, reflux.
Synlett 2011, No. 16, 2329–2334 © Thieme Stuttgart · New York

LETTER
Diversity-Oriented Synthesis of Biaryl Derivatives
Product (Yield)
2331
Table 1 Preparation of Homoallyl 1,3-Dienes and Aromatized Products
Substrate
Product (Yield)
CO2Me
CO2Me
MeO
OMe
MeO
MeO
13
OMe
OMe
14 (73%)
24 (75%)
CO2Me
CO2Me
MeO
16
MeO
MeO
20 (65%)
25 (66%)
CO2Me
CO2Me
Cl
17
Cl
Cl
21 (75%)
26 (60%)
CO2Me
CO2Me
Br
18
Br
Br
27 (72%)
22 (88%)
CO2Me
CO2Me
I
19
I
I
23 (86%)
28 (82%)
The dienes 14 were then subjected to Diels–Alder reaction
with dienophiles in toluene under reflux to deliver the cor-
responding adducts. Even though we used a catalytic
amount of 1,4-hydroquinone during the cycloaddition re-
action to prevent polymerization of the diene, the results
were not encouraging. However, when the reaction was
carried out in toluene at 90 °C for 24 hours, formation of
the Diels–Alder adduct was observed (TLC monitoring).
The adduct was then subjected directly to aromatization
with MnO2 in 1,4-dioxane and also with DDQ in toluene.
We observed that the DDQ/toluene conditions gave better
yields of the aromatized products (Table 1).
CO2Me
CO2Me
CO2Me
CO2Me
(ii)
X
X
Y
Y
(iii)
(i) a, b
CO2Me
CO2Me
X
X
Y
Y
X = OMe, Y = OMe
X = OMe, Y = H
X = I, Y = H
X = Br, Y = H
X = Cl, Y = H
In a second strategy, 1-ethynyl-4-methoxybenzene (16)
was subjected to an ethylene-mediated (1 bar pressure)
cross-metathesis sequence using the Grubbs second-gen-
eration catalyst 9 in toluene at 90 °C to generate the re-
quired diene. The disappearance of the acetylenic proton
and the appearance of new peaks at d = 5.12–5.29 ppm
and at d = 6.66 ppm in 1H NMR spectral data indicated the
Scheme 4 Reagents and conditions: (i) (a) Grubbs II, C2H4, CH2Cl2,
r.t., 24 h; (b) Grubbs II, C2H4, toluene, 90 °C 24 h; (ii) toluene, 90 °C,
24 h; (iii) DDQ toluene, reflux, 36 h.
Synlett 2011, No. 16, 2329–2334 © Thieme Stuttgart · New York

2332
S. Kotha, V. Seema
LETTER
formation of the diene 30. Along similar lines, 1-ethynyl- Miyaura cross-coupling (Scheme 5) with boronic acids
4-iodobenzene (19) was subjected to cross-metathesis such as 4-methoxyphenyl boronic acid, 4-cyanophenyl
with ethylene using the Grubbs second-generation cata- boronic acid, 4-acetylphenyl boronic acid, and 4-
lyst 9 in CH2Cl2 at room temperature for 24 hours under formylphenyl boronic acid using a Pd(0) catalyst in tolu-
nitrogen, and complete conversion of the starting material ene and THF (1:1 ratio, Figure 4) to generate terphenyl
was observed. Next, 4-chloro- and 4-bromophenylacety- derivatives.
lene derivatives were subjected to cross-enyne metathesis
with ethylene in the presence of the Grubbs second-gener-
ation catalyst to generate the corresponding dienes
(Scheme 4).
CO2Me
CO2Me
(i)
CO2Me
CO2Me
Based on the above experiments it was concluded that tol-
X
R
uene is a better solvent for cross-enyne metathesis under
ethylene as well as 1,5-hexadiene conditions with sub-
strates such as 3,4-dimethoxyphenylacetylene (13) and 4-
methoxyphenylacetylene (16), whereas CH2Cl2 seems to
be a better solvent for halogenated phenylacetylene sub-
strates 17–19. The dienes obtained during the cross-
metathesis were subjected to Diels–Alder reaction with a
dienophile such as DMAD in toluene, at 90 °C for 24
hours to deliver the corresponding adducts.
37 X = Br
38 X = I
R = CHO, COMe, OMe, CN
Scheme
C6H4B(OH)2, Na2CO3.
5
Reagents and conditions: (i) Pd(PPh3)4, 4-R-
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
Table 2 Aromatization of Diels–Alder Products with DDQ in Tol-
uene at Reflux
Substrate Product (Yield)
Product (Yield)
CO2Me
CO2Me
CN
COMe
CHO
OMe
13
39 I = 86%
Br = 78%
40 I = 58%
Br = 52%
41 I = 84%
Br = 80%
42 I = 80%
Br = 74%
MeO
MeO
OMe
OMe
Figure 4 Preparation of terphenyl derivatives via SM cross-coupling
starting with 37 or 38
29 (75%)
34 (66%)
CO2Me
CO2Me
16
In conclusion, we have demonstrated that cross-enyne
metathesis of 1,5-hexadiene or ethylene with phenylacet-
ylene derivatives followed by a Diels–Alder reaction and
aromatization sequence furnishes biaryl derivatives.
These biaryl derivatives are useful intermediates to
prepare highly functionalized terphenyl derivatives via
Suzuki–Miyaura cross-coupling. The strategy demon-
strated here has several diversity points.18 Firstly, the
cross-metathesis partners can be varied and a second di-
versity point involves the utilization of various dieno-
philes during the Diels–Alder reaction. A third diversity
point is the variation of the boronic acids during the Suzu-
ki–Miyaura reaction. Since more than thousand boronic
acids are commercially available, our approach to biaryl
(or terphenyl) building blocks can provide a library of
these privileged molecules.
MeO
MeO
30 (81%)
35 (62%)
CO2Me
17
CO2Me
Cl
Cl
31 (70%)
36 (65%)
CO2Me
CO2Me
18
Br
Br
32 (83%)
37 (82%)
CO2Me
CO2Me
19
I
I
General Procedure for the Preparation of Homoallyl Dienes
To a degassed solution of 4-ethynyl-1,2-dimethoxybenzene (13,
100 mg, 0.61 mmol) and 1,5-hexadiene (100 mg, 1.22 mmol) in tol-
uene (10 mL) was added Grubbs second-generation catalyst (20 mg,
4 mol%), and the reaction mixture was heated at reflux for 1 h. At
the conclusion of the reaction (TLC monitoring) the reaction mix-
ture was concentrated, and the crude product was purified by a flash
33 (63%)
38 (86%)
The Diels–Alder products were subjected to aromatiza-
tion with DDQ in toluene at reflux (Table 2). Finally,
these aromatized products were subjected to Suzuki–
Synlett 2011, No. 16, 2329–2334 © Thieme Stuttgart · New York

LETTER
Diversity-Oriented Synthesis of Biaryl Derivatives
2333
column chromatography using PE as eluent to afford 14 (110 mg,
74%) as a colorless liquid.
132.1, 133.5, 138.2, 147.5. HRMS(Q-ToF): m/z calcd for C15H19O
[M + H]+: 215.1436; found: 215.1433.
General Procedure for the Diels–Alder Reaction of Homoallyl
Butadiene Derivatives Followed by Aromatization
Compound 24
IR (neat): 1025, 1262, 1519, 1729, 2925 cm–1. 1H NMR (400 MHz,
CDCl3): d = 2.40 (dd, J1 = 8.8 Hz, J2 = 1.2 Hz, 2 H), 2.76 (t, J = 2.4
Hz, 2 H), 3.92 (s, 3 H), 3.94 (s, 3 H), 3.95 (s, 3 H), 3.97 (s, 3 H),
4.92–5.07 (m, 2 H), 5.81–5.89 (m, 1 H), 6.94 (d, J = 8.4 Hz, 1 H),
7.08 (d, J = 2.0 Hz, 1 H), 7.13–7.17 (m, 1 H), 7.58 (d, J = 2.0 Hz, 1
H), 8.02 (d, J = 1.6 Hz, 1 H). 13C NMR (100 MHz, CDCl3):
d = 33.0, 35.4, 52.8, 56.14, 56.18, 56.2, 110.4, 111.6, 115.6, 119.8,
126.2. 128.9, 132.0, 132.4, 133.2, 137.5, 142.2, 149.5, 166.6, 169.8.
HRMS(Q-ToF): m/z calcd for C22H24O6 [M + Na]+: 407.1471;
found: 407.1482.
To a solution of the diene 14 (110 mg, 0.45 mmol) in toluene (5 mL)
was added dimethyl acetylene dicarboxylate (128 mg, 0.9 mmol),
and the reaction mixture was heated at 90 °C for 15 h. At the con-
clusion of the reaction (TLC monitoring) the solvent was removed
under reduced pressure, and the crude product was purified by a sil-
ica gel column chromatography (EtOAc–PE, 0.5:9.5) to afford the
adduct as a semisolid. Oxidation of the adduct was carried out with
MnO2 (116 mg, 13.05 mmol) in refluxing 1,4-dioxane (14 mL) for
30 h. The solvent was removed under reduced pressure, and the
crude product was purified by flash silica gel column chromatogra-
phy (EtOAc–PE, 0.5:9.5) to afford the aromatized product 24 (130
mg, 75%) as a semisolid.
Compound 26
IR (neat): 1013, 1266, 1435, 1640, 2952 cm–1. 1H NMR (400 MHz,
CDCl3): d = 2.40 (dd, J1 = 7.6 Hz, J2 = 1.2 Hz, 2 H), 3.80 (t, J = 4.8
Hz, 2 H), 3.92 (s, 3 H), 3.96 (s, 3 H), 4.99–5.30 (m, 1 H), 5.81–5.89
(m, 1 H), 7.43 (d, J = 4.8 Hz, 1 H), 7.43 (d, J = 4.8 Hz, 1 H), 7.53
(d, J = 4.4 Hz, 1 H), 7.59 (d, J = 2.0 Hz, 2 H), 8.03 (d, J = 2.0 Hz, 2
H). 13C NMR (100 MHz, CDCl3): d = 32.9, 35.3, 52.7, 53.6, 115.7,
126.4, 128.5, 128.8, 129.2, 132.2, 134.0, 134.4, 137.3, 137.8, 140.3,
140.9, 166.3, 169.7. HRMS(Q-ToF): m/z calcd for C20H19O4Cl
[M + Na]+: 381.0882; found: 381.0870.
General Procedure for the Preparation of 1,3-Dienes and Diels–
Alder Reaction Followed by Aromatization
A solution of 13 (100 mg, 0.61 mmol) in toluene (10 mL) was de-
gassed with N2 for 10 min and then Grubbs second-generation cat-
alyst (26 mg, 5 mol%) was added. The reaction mixture was kept
under 1 atm pressure of ethylene (balloon pressure) and stirred at
90 °C for 24 h. At the conclusion of the reaction (TLC monitoring)
the solvent was concentrated, and the crude product was purified by
a flash silica gel column chromatography (EtOAc–PE, 0.5:9.5) to
afford 29 (85 mg, 73%) as a brownish liquid. Later, diene 29 (95
mg, 0.5 mmol) was dissolved in toluene (10 mL), dimethyl acety-
lene dicarboxylate (142 mg, 1.0 mmol) was added, and the mixture
was heated at 90 °C for 24 h. At the conclusion of the reaction (TLC
monitoring) the adduct was oxidized with DDQ (181 mg, 0.79
mmol) in refluxing toluene (10 mL) for 36 h. The solvent was re-
moved under reduced pressure, and the crude product obtained was
purified by flash silica gel column chromatography with 5%
EtOAc–PE to afford the aromatized product 34 (110 mg, 66%) as a
semisolid.
Compound 34
IR (neat): 738, 1025, 1266, 1731, 2954 cm–1. 1H NMR (400 MHz,
CDCl3): d = 3.92 (s, 3 H), 3.93 (s, 3 H), 3.95 (d, J = 7.2 Hz, 6 H),
6.96 (d, J = 8.0 Hz, 2 H), 7.10 (d, J = 1.2 Hz, 1 H), 7.18 (d, J1 = 5.2
Hz, 1 H), 7.69 (d, J = 2.0 Hz, 1 H), 7.83 (d, J = 1.2 Hz, 1 H). 13
C
NMR (100 MHz, CDCl3): d = 56.8, 52.9, 56.1, 56.2, 110.2, 110.3,
111.5, 119.9, 126.9, 129.1, 131.8, 133.9, 144.4, 149.5, 149.7, 167.6,
168.8. HRMS(Q-ToF): m/z calcd for C18H19O6 [M + H]+: 331.1182;
found: 331.1185.
Compound 38
IR (neat): 748, 819, 1735, 2853 cm–1. 1H NMR (400 MHz, CDCl3):
d = 3.93 (s, 3 H), 3.94 (s, 3 H), 7.26–7.36 (m, 2 H), 7.69–7.79 (m, 1
H), 7.78–7.86 (m, 4 H). 13C NMR (100 MHz, CDCl3): d = 52.8,
52.9, 94.7, 127.2, 129.1, 130.0, 133.3, 138.5, 138.6, 143.3, 167.6,
168.3. HRMS(Q-ToF): m/z calcd for C16H14O4I [M + H]+:
393.9937; found: 393.9933.
General Procedure for Cross-Coupling Reactions
A solution of 37 (74 mg, 0.21 mmol) in THF–toluene (1:1) mixture,
4-methoxy phenylboronic acid (63 mg, 0.48 mmol) and aq Na2CO3
(44 mg, 0.42 mmol) was degassed with N2 for 20 min, and
Pd(PPh3)4 (9.7 mg, 4 mol%) was added. The reaction mixture was
then heated for 6 h at 90 °C. At the conclusion of the reaction (TLC
monitoring) the reaction mixture was diluted with H2O and extract-
ed with CH2Cl2 (4 × 50 mL). The combined organic layers were
washed with H2O, brine, and dried over Na2SO4. The solvent was
evaporated, and the crude product was purified by silica gel column
chromatography EtOAc–PE, 0.5:9.5) to give the desired cross-
coupling product 39 (68 mg, 86%) as a white solid.
Compound 39
Mp 150–152 °C. IR (KBr): 743, 819, 1734, 2852 cm–1. H NMR
1
(400 MHz, CDCl3): d = 3.87 (s, 3 H), 3.93 (s, 3 H), 3.95 (s, 3 H),
7.01, (d, J = 4.0 Hz, 2 H), 7.58 (d, J = 4.8 Hz, 2 H), 7.67 (d, J = 2.0
Hz, 2 H), 7.80 (d, J = 1.6 Hz, 2 H), 7.86 (d, J = 8.0 Hz, 2 H), 7.94
(d, J = 1.2 Hz, 1 H). 13C NMR (100 MHz, CDCl3): d = 26.7, 29.7,
55.4, 114.3, 126.7, 126.8, 127.3, 127.4, 127.8, 128.2, 128.8, 129.0,
129.1, 133.9, 140.9, 159.2. HRMS(Q-ToF): m/z calcd for C23H21O5
[M + H]+: 377.1398; found: 377.1389.
Compound 15
IR (neat): 790, 1220, 1590, 2985 cm–1. 1H NMR (400 MHz, CDCl3):
d = 3.92 (s, 3 H), 3.95 (s, 3 H), 6.95 (d, J = 4.4 Hz, 2 H), 7.11–7.16
(m, 1 H), 7.32 (t, J = 7.8 Hz, 1 H), 7.42 (t, J = 8.2 Hz, 2 H), 7.56 (d,
J = 4.4 Hz, 2 H). 13C NMR (100 MHz, CDCl3): d = 53.5, 56, 110,
111, 119, 127, 128, 134, 141, 148, 149. HRMS(Q-ToF): m/z calcd
for C14H15O2 [M + H]+: 215.1078; found: 215.1072.
Compound 40
Mp 138–140 °C. IR (KBr): 743, 819, 1734, 2852 cm–1. H NMR
1
(400 MHz, CDCl3): d = 3.94 (s, 3 H), 3.96 (s, 3 H), 7.71–7.94 (m, 5
H), 7.81 (d, J = 2.0 Hz, 2 H), 7.87 (d, J1 = 8.4 Hz, 2 H), 7.95 (d,
J = 2.0 Hz, 2 H). 13C NMR (100 MHz, CDCl3): d = 52.9,
55.5,114.4, 114.5, 119.0, 127.3, 127.6, 128.0, 128.7, 129.8, 132.9,
133.3, 137.3, 139.4, 141.1, 143.5, 153.6, 156.8. HRMS(Q-ToF):
m/z calcd for C23H17NO4 [M + Na]+: 394.1068; found: 394.1055.
Compound 20
1
IR (neat): 742, 811, 1263, 1514, 1601, 2929 cm–1. H NMR (400
MHz, CDCl3): d = 2.15–2.23 (m, 4 H), 3.81 (s, 3 H), 4.95–5.03 (m,
3 H), 5.12 (d, J = 1.6 Hz,1 H), 5.64–5.71 (m, 1 H), 5.78–5.85 (m, 1
H), 6.30 (d, J = 15.6 Hz, 1 H), 6.86 (d, J = 1.2 Hz, 2 H), 7.25 (d,
J = 0.9 Hz, 2 H). 13C NMR (100 MHz, CDCl3): d = 21.1, 32.4, 33.6,
55.3, 60.5, 113.5, 114.1, 114.3, 115.0, 126.8, 128.2, 128.8, 129.4,
Compound 41
Mp 157–159 °C. IR (KBr): 740, 823, 1682, 1730, 2853 cm–1. H
1
NMR (400 MHz, CDCl3): d = 2.65 (s, 3 H), 3.94 (s, 3 H), 3.95 (s, 3
H), 7.73–7.74 (m, 7 H), 7.83 (dd, J1 = 2.8 Hz, J2 = 8.0 Hz, 1 H), 7.96
Synlett 2011, No. 16, 2329–2334 © Thieme Stuttgart · New York

2334
S. Kotha, V. Seema
LETTER
(9) For recent reviews please, see: (a) Kotha, S.; Lahiri, K.
(s, 1 H), 8.06 (d, J = 8.0 Hz, 2 H). 13C NMR (100 MHz, CDCl3):
d = 52.8, 52.9, 127.2, 128.0, 129.1, 129.3, 129.9, 130.3, 133.3,
136.2, 138.9, 140.0, 143.6, 144.9, 167.7, 168.4, 197.8. HRMS(Q-
ToF): m/z calcd for C24H20O5 [M + Na]+: 411.1208; found:
411.1198.
Synlett 2007, 2767. (b) Grubbs, R. H. Tetrahedron 2004, 60,
7117. (c) Deiters, A.; Martin, S. F. Chem. Rev. 2004, 104,
2199. (d) McReynolds, M. D.; Dougherty, J. M.; Hanson, P.
R. Chem. Rev. 2004, 104, 2239. (e) Schrock, R. R.;
Hoveyda, A. H. Angew. Chem. Int. Ed. 2003, 42, 4592.
(f) Kotha, S.; Sreenivasachary, N. Indian J. Chem., Sect. B:
Org. Chem. Incl. Med. Chem. 2001, 40, 763.
Compound 42
Mp 156–160 °C. IR (KBr): 780, 840, 1726, 2953 cm–1. H NMR
1
(400 MHz, CDCl3): d = 3.94 (s, 3 H), 3.96 (s, 3 H), 7.77 (d, J = 16.0
Hz, 2 H), 7.80–7.81 (m, 4 H), 7.84 (d, J = 18.4 Hz, 3 H), 7.79 (dd,
J1 = 13.2 Hz, J2 = 8.4 Hz, 2 H), 10.08 (s 1 H). 13C NMR (100 MHz,
CDCl3): d = 52.8, 52.9, 127.7, 127.9, 128.1, 129.3, 130.5, 133.3,
135.6, 135.1, 139.1, 139.9, 143.5, 146.3, 167.7, 168.4, 191.9.
HRMS(Q-ToF): m/z calcd for C23H19O5 [M + H]+: 375.1232; found:
375.1233.
(g) Samojłowicz, C.; Bieniek, M.; Grela, K. Chem. Rev.
2009, 109, 3708.
(10) (a) Kotha, S.; Seema, V.; Singh, K.; Deodher, K. D.
Tetrahedron Lett. 2010, 51, 2341. (b) Kotha, S.; Shah, V.
R.; Mandal, K. Adv. Synth. Catal. 2007, 1159. (c) Kotha,
S.; Dipak, M. K. Chem. Eur. J. 2006, 12, 4446. (d) Kotha,
S.; Mandal, K. Tetrahedron Lett. 2004, 45, 2585.
(11) (a) Kotha, S.; Meshram, M.; Tiwari, A. Chem. Soc. Rev.
2009, 38, 2065. (b) Kotha, S.; Mandal, K. Chem. Asian. J.
2009, 4, 354. (c) Kotha, S.; Mandal, K.; Banerjee, S.;
Mobin, S. M. Eur. J. Org Chem. 2007, 1244.
(12) (a) Fringulli, F.; Taticchi, A. Dienes in the Diels–Alder
Reaction; Wiley: New York, 1990. (b) Paquette, L. A.
Comprehensive Organic Synthesis, Vol. 5; Pergamon:
Oxford, 1991. (c) Kaliappan, K. P.; Velayutham, R. J. Org.
Chem. 2007, 72, 6116. (d) Hansen, E. C.; Lee, D. Acc.
Chem. Res. 2006, 39, 509. (e) Jayakanthan, K.; Vankar, Y.
D. Org. Lett. 2005, 7, 5441. (f) Diver, S. T.; Giessert, A. J.
Chem. Rev. 2004, 104, 1317. (g) Poulsen, C. S.; Madsen, R.
Synthesis 2003, 1. (h) Mori, M. Top. Organomet. Chem.
1999, 1, 133.
(13) (a) Kotha, S.; Khedkhar, P. Synthesis 2008, 2925.
(b) Kotha, S.; Singh, K. Eur. J. Org. Chem. 2007, 5909.
(c) Middleton, M. D.; Peppers, B.; Diver, S. Tetrahedron
2006, 62, 10528. (d) Middleton, M. D.; Diver, S.
Tetrahedron Lett. 2005, 46, 4039. (e) Tonogaki, K.; Mori,
M. Tetrahedron Lett. 2002, 43, 2235. (f) Smulik, J. A.;
Diver, S. Org. Lett. 2000, 2, 2271. (g) Schwab, P.; France,
M. B.; Ziller, J. W.; Grubbs, R. H. Angew. Chem., Int. Ed.
Engl. 1995, 34, 2039.
(14) (a) Kotha, S.; Chavan, S. J. Org. Chem. 2010, 75, 4319.
(b) Kotha, S.; Khedkher, P. J. Org. Chem. 2009, 74, 5667.
(c) Ikeuchi, Y.; Saitoh, T.; Taguchi, T.; Hanzawa, Y.
Tetrahedron Lett. 2007, 48, 2477.
Acknowledgment
We would like to acknowledge the DST for financial support. S.V.
thanks IIT-Bombay and UGC-New Delhi for the award of a re-
search fellowship. S.K. thanks the DST for the award of a J. C. Bose
fellowship.
References
(1) (a) Herbert, W.; Yu-Peng, H.; Hao, T.; Lars, A. A.; Hans-
Dieter, A. Chem. Commun. 2008, 5562. (b) Nussbaum, F.
V.; Brands, M.; Hinzen, B.; Weigand, S.; Habich, D. Angew.
Chem. Int Ed. 2006, 45, 5072. (c) Hassan, J.; Sevignon, M.;
Gozzi, C.; Schulz, E.; Lemaire, M. Chem. Rev. 2002, 102,
1359. (d) Bringmann, M.; Gunther, C.; Ochse, M.; Schupp,
O.; Tasler, S. J. Nat. Prod. 2001, 82, 249.
(2) Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem. Rev.
2003, 103, 893.
(3) Larsen, R. D.; King, A.; Chen, C. Y.; Corley, E. G.; Foster,
B. S.; Roberts, F. E.; Yang, C.; Lieberman, D. R.; Reamer,
R. A.; Tschaen, D. M.; Verhoeven, T. R.; Reider, P. J.
J. Org. Chem. 1994, 59, 6391.
(4) (a) Glascalid, T. N.; Kappe, C. O. Adv. Synth. Catal. 2010,
352, 3089. (b) Goosen, L. J.; Thomas, K. J. Org. Chem.
2008, 73, 8631. (c) Bhowmik, S.; Horsman, G. P.; Bolin,
J. T. J. Biol. Chem. 2007, 282, 36377. (d) Tsunoda, T.;
Yamazaki, A.; Mase, T.; Sakamoto, S. Org. Process Res.
Dev. 2005, 9, 593. (e) Cepanec, I. Synthesis of Biaryls;
Elsevier: New York, 2004. (f) Bringmann, G.; Menche, D.
Angew. Chem. Int. Ed. 2001, 40, 1687. (g) Kamikawa, K.;
Watanabe, T.; Daimon, A.; Uemura, M. Tetrahedron 2000,
56, 2325.
(5) (a) Bhalla, V.; Tejpal, R.; Kumar, M.; Seth, A. Inorg. Chem.
2009, 48, 11677. (b) Bhalla, V.; Kumar, M. Org. Lett. 2010,
12, 628. (c) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986,
25, 508.
(6) (a) Venuti, M. C. J. Org. Chem. 1981, 46, 3124.
(b) Kolotuchin, S. V.; Meyers, A. I. J. Org. Chem. 1999, 64,
7921. (c) McCarthy, M.; Guiry, P. J. Tetrahedron 2001, 57,
3809.
(15) (a) Kotha, S.; Lahiri, K. Eur. J. Org. Chem. 2007, 1221.
(b) Kotha, S.; Mandal, K.; Arora, K. K.; Pedireddi, V. V.
Adv. Synth. Catal. 2005, 347, 1215. (c) Kotha, S.; Lahiri,
K.; Kashinath, D. Tetrahedron 2002, 58, 9632.
(d) Miyaura, N. Advances in Metal-Organic Chemistry, Vol.
6; Liebeskind, L. S., Ed.; Jai Press: London, 1998, 187.
(e) Suzuki, A. J. Organomet. Chem. 1997, 36, 2163.
(16) Kotha, S.; Tafesh, A.; Davenport, K.; Ortiz, P. Indian J.
Chem., Sect. B: Org. Chem. Incl. Med. Chem. 2001, 40,
1166.
(17) Banerjee, S. PhD Thesis; Indian Institute of Technology
Bombay: Mumbai, 2007.
(18) (a) Kaliappan, K. P.; Subrahmanyam, A.; Palanichamy, K.
Chem. Eur. J. 2010, 8545. (b) Schreiber, S. L. Nature
(London) 2009, 457, 153. (c) Mishra, J. K. G.; Panda, G.
J. Comb. Chem. 2007, 9, 321. (d) Kotha, S.; Mandal, K.;
Tiwari, A.; Mobin, S. M. Chem. Eur. J. 2006, 8024.
(e) Burke, M. D.; Berger, E. M.; Schreiber, S. L. J. Am.
Chem. Soc. 2004, 126, 14095. (f) Burke, M. D.; Schreiber,
S. L. Angew. Chem. Int. Ed. 2003, 43, 46. (g) Burke, M. D.;
Lalic, G. Chem. Biol. 2002, 9, 535. (h) Schreiber, S. L.;
Nicolaou, K. C.; Davies, K. Chem. Biol. 2002, 9, 1.
(i) Schreiber, S. L. Science 2000, 287, 1964.
(7) Noyori, R.; Takaya, H. Acc. Chem. Res. 1990, 23, 345.
(8) (a) Handbook of Organopalladium Chemistry for Organic
Synthesis; Negishi, E.; de Meijere, A., Eds.; Wiley
Interscience: New York, 2002. (b) Metal-Catalyzed Cross-
Coupling Reactions, Vol. 1 and 2; de Meijere, A.; Diederich,
F., Eds.; Wiley-VCH: Weinheim, 2004. (c) Kotha, S.;
Brahmachary, E.; Lahiri, K. Eur. J. Org. Chem. 2005, 4741.
(d) Liu, C. Y.; Gavryushin, A.; Knochel, P. Chem. Asian J.
2007, 2, 1020.
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