Synthesis of 4,5-diaryl-1,2,3-benzenetricarboxylates by reaction of 4-hydroxycyclopent-2-en-1-one-2-carboxylates with dimethyl acetylenedicarboxylate

Article abstract of DOI:10.1016/j.tet.2007.02.111

4,5-Diaryl-1,2,3-benzenetricarboxylates were prepared by cycloaddition of 4-hydroxycyclo-2-penten-1-one-2-carboxylates with dimethyl acetylenedicarboxylate.

Full text of DOI:10.1016/j.tet.2007.02.111

Tetrahedron 63 (2007) 4080–4086
Synthesis of 4,5-diaryl-1,2,3-benzenetricarboxylates by reaction
of 4-hydroxycyclopent-2-en-1-one-2-carboxylates with
dimethyl acetylenedicarboxylate
a,b
Muhammad Sher, Christine Fischer, Helmut Reinke and Peter Langer
a,b
a
a,b,*
a
Institut f u€ r Chemie, Universit a€ t Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
Leibniz-Institut f u€ r Katalyse e. V. an der Universit a€ t Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
b
Received 25 January 2007; revised 19 February 2007; accepted 26 February 2007
Available online 1 March 2007
Abstract—4,5-Diaryl-1,2,3-benzenetricarboxylates were prepared by cycloaddition of 4-hydroxycyclo-2-penten-1-one-2-carboxylates with
dimethyl acetylenedicarboxylate.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Functionalized arenes represent important building blocks
in organic and medicinal chemistry. An important strategy
The reaction of the dianion of methyl acetoacetate 1a
with benzil (2a) regioselectively afforded the 3-hydroxy-5-
oxo-2,3-diphenylcyclopent-1-ene-1-carboxylate 3a. The
reactions were carried as one-pot transformations: the
condensation of the dianion with 2a gave an open-chained
product, which underwent cyclization upon addition of
silica gel to the reaction mixture and reflux. Notably, the cy-
clization exclusively afforded the hydroxylated product 3a
and not the corresponding fulvenone (by elimination of a sec-
ond equivalent of water). This can be explained by the unsta-
ble nature of the fulvenone, due to its antiaromatic character.
1
for the synthesis of functionalized benzene derivatives relies
on the [4+2] cycloaddition of 1,3-dienes with alkynes and
subsequent oxidation. It is known for a long time that
2
the reaction of alkynes with heterocyclic dienes such as
furans results in the formation of bridged oxacycles, which
can be transformed into functionalized benzene derivatives
3
by acidic hydrolysis. A related strategy has been reported
for the cycloaddition of cyclopentadienones (fulvenones)
4
with alkynes. These reactions proceed by cycloaddition
and subsequent extrusion of carbon monoxide. The
acid-mediated reaction of alkynes with 4-hydroxycyclo-
The reaction of 3a with dimethyl acetylenedicarboxylate
(DMAD), in the presence of catalytic amounts of p-toluene-
sulfonic acid (PTSA, 5 mol %), afforded 4,5-diphenyl-1,2,3-
benzenetricarboxylate 4a (Scheme 1, Table 1). The reactions
2
-penten-1-ones, which represents precursors of highly
reactive fulvenones, has been reported to give benzene
5
6
derivatives. We have recently reported the synthesis of
7
5d
4
-hydroxycyclo-2-penten-1-one-2-carboxylates by cycli-
zation of 1,2-diketones with 1,3-dicarbonyl dianions or
,3-bis(silyl enol ethers) (masked dianions). Herein, we
report the synthesis of a variety of new 4-hydroxycyclo-
-penten-1-one-2-carboxylates and their transformation
were carried out according to a known procedure. The
choice of the acid played an important role. The use of concd
1
sulfuric acid or Lewis acids (BF $OEt , TiCl ) resulted in
3
2
4
5
d
decomposition. The formation of 4a can be explained by
PTSA-catalyzed elimination of water from 3a to give
a highly reactive fulvenone. The [4+2] cycloaddition of
the latter with DMAD afforded a bridged cycloadduct,
which underwent extrusion of carbon monoxide and aroma-
tization to give the final product.
2
into novel 4,5-diaryl-1,2,3-benzenetricarboxylates by acid-
mediated cycloaddition.
The scope of the reaction was studied (Table 1). The reaction
of the dianions of b-ketoesters 1a–d with 1,2-diketones
Keywords: Arenes; Cyclizations; Diels–Alder reactions; Dianions; Di-
ketones.
2a–d regioselectively afforded the 3-hydroxy-5-oxo-2,3-
diarylcyclopent-1-ene-1-carboxylates 3a–i. The reaction of
*
Corresponding author. Tel.: +49 381 4986410; fax: +49 381 4986412;
e-mail: peter.langer@uni-rostock.de
0
040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.02.111

M. Sher et al. / Tetrahedron 63 (2007) 4080–4086
4081
O
O
O
R1
O
OR2
Ar
CO2R2
R1
1
a-d
a
O
Ar
HO
Ar
+
Ar
3a-i
2a-d
b
O
MeO2C
R1
CO2Me
CO2R2
R1
DMAD
CO2R2
_
CO
Ar
Ar
Ar
Ar
4a-i
DMAD
=
MeO2C
CO2Me
Scheme 1. Synthesis of 4,5-diaryl-1,2,3-benzenetricarboxylates 4a–i, (a):
ꢀ
ꢀ
(
1) LDA (2.3 equiv), THF, 0 C, 1 h; (2) 2, ꢁ78/20 C, 12 h; (3) addition
of SiO , THF, reflux, 19–26 h and (b): DMAD (8.0 equiv), PTSA (5 mol %),
toluene, 100 C.
2
ꢀ
Figure 1. ORTEP plot of 3b.
cyclopentenones 3 with dimethyl acetylenedicarboxylate
explained by cyclization of 3c with benzil (2a) based on
the aldol reaction and formation of a semi-ketal.
(
DMAD), in the presence of catalytic amounts of p-toluene-
sulfonic acid (PTSA, 5 mol %), afforded the 4,5-diaryl-
,2,3-benzenetricarboxylates 4a–i (Scheme 1, Table 1).
1
The reaction of the dianion of N,N-diethyl-acetylacetic
amide (1e) with 2a afforded the 3-hydroxycyclo-4-penten-
1-one-2-carboxylic amide 6 and not a 4-hydroxycyclo-2-
penten-1-one-2-carboxylic amide (as observed for 3a–i)
(Scheme 2). The formation of the different positional iso-
mers can be explained by the steric interaction between
the phenyl and the (rather rigid) amide group and by the
relatively low electron-withdrawing effect of the amide
(compared to the ester). The PTSA mediated cycloaddition
of 6 with DMAD afforded phthalate 7.
These experiments show that the presence of bromide or
methoxy groups located at the aryl groups is compatible with
the reaction conditions. All reactions proceeded in moderate
to good yields. The PTSA mediated reaction of DMAD with
methyl 3-hydroxy-5-oxo-2,3-dimethylcyclopent-1-ene-1-
carboxylate, prepared from butane-2,3-dione, resulted in
the formation of a complex mixture. Likewise, the reaction
of 3a with maleic anhydride proved to be unsuccessful
(
decomposition).
The structures of 3b and 4c were independently confirmed
by X-ray crystal structure analysis (Figs. 1 and 2). In case of
In conclusion, an efficient synthesis of 4,5-diaryl-1,2,3-
benzenetricarboxylates by cycloaddition of 4-hydroxycyclo-
2-penten-1-one-2-carboxylates with dimethyl acetylenedi-
carboxylate was reported.
8
3
c, the interesting side-product 5 was isolated in low yield.
The formation of 5, the structure of which was also con-
8
firmed by X-ray crystal structure analysis (Fig. 3), can be
Table 1. Products and yields
1
2
a
a
1
2
3 and
4
R
R
Ar
Yield Yield
of 3 (%) of 4 (%)
a
b
c
d
a
c
a
c
b
a
a
a
a
b
b
c
a
b
c
d
e
f
g
h
i
H
H
H
Et
H
H
H
H
H
Me
Et
i-Pr Ph
Et
Me
i-Pr 4-MeC
Me
i-Pr 4-(MeO)C
Et 4-BrC
Ph
Ph
51
60
41
55
36
52
32
47
42
46
46
46
33
86
40
40
46
68
b
c
d
Ph
4-MeC
6
H
H
4
4
6
4-(MeO)C
6
H
H
4
c
d
6
4
6 4
H
a
b
c
d
Isolated yields.
Besides, a small amount of 5 was isolated (vide infra).
Mixture of diastereomers: dr¼1:1.
A small amount of impurity could not be separated.
O
HO
Ph
H
CO2iPr
Ph
HO
O
Ph Ph
5
Figure 2. ORTEP plot of 4c.

4082
M. Sher et al. / Tetrahedron 63 (2007) 4080–4086
extracted with diethyl ether. The combined organic layers
were dried (Na SO ), filtered and the filtrate was concen-
2
4
trated in vacuo. The residue was purified by chromatography
silica gel, EtOAc and heptane).
(
3
.1.1. Methyl 3-hydroxy-5-oxo-2,3-diphenylcyclopent-1-
ene-1-carboxylate (3a). Starting with methyl acetoacetate
1.12 mL, 10.46 mmol, 1.1 equiv), diisopropylamine (3.21 mL,
(
2
2
2.82 mmol, 2.5 equiv), n-butyllithium (8.74 mL, 22.82 mmol,
.5 equiv) and benzil (2.00 g, 9.51 mmol), 3a was isolated
by chromatography (heptane/ethyl acetate) as a slightly
yellow solid (1.50 g, 51%). Reaction time: 24 h; mp 129–
ꢀ
1
1
30 C. H NMR (250 MHz, CDCl ): d¼2.98 (d, 1H,
3
2
J¼18 Hz, HCH–CO), 3.11 (d, 1H, J¼18 Hz, HCH–CO),
13
3
.76 (s, 3H, OCH ), 7.17–7.44 (m, 10H, Ph); C NMR
3
(
(
62 MHz, CDCl ): d¼52.4 (CH ), 55.0 (CH –CO), 80.7
3
3
2
COH), 124.5 (2CH ), 128.6 (CH ), 128.2 (2CH ), 128.6
Ph Ph Ph
(2CH ), 128.8 (2CH ), 130.5 (CH ), 131.2, 134.3, 142.3,
Ph Ph Ph
1
2
1
64.7, 174.1, 200.0 (C); IR (KBr): ~n ¼3357 (w), 3060 (w),
951 (m), 1735 (s), 1686 (s), 1434 (m), 1343 (s), 1229 (s),
059 (m), 779 (s), 704 (s), 513 (m) cm ; MS (EI, 70 eV):
ꢁ
1
+
Figure 3. ORTEP plot of 5.
m/z (%): 308.1 (M , 22), 276.1 (100), 208 (18), 129 (27),
05 (56); elemental analysis: calcd (%) for C H O
9 16 4
1
1
(308.327): C 74.01, H 5.23; found: C 73.90, H 5.23.
O
O
3
.1.2. Ethyl 3-hydroxy-5-oxo-2,3-diphenylcyclopent-1-
O
O
NEt2
Ph
ene-1-carboxylate (3b). Starting with ethyl acetoacetate
(1.32 mL, 10.46 mmol, 1.1 equiv), diisopropylamine (3.35 mL,
23.77 mmol, 2.5 equiv), n-butyllithium (9.51 mL, 23.77 mmol,
1
e
a
NEt2
O
OH
+
Ph
Ph
2
.5 equiv) and benzil (2.00 g, 9.51 mmol), 3b was isolated
by chromatography (heptane/ethyl acetate) as a slightly yel-
Ph
O
a
6
(43%)
ꢀ
2
low solid (1.82 g, 60%); mp 78–80 C. Reaction time: 26 h.
b
1
3
H NMR (300 MHz, CDCl ): d¼1.12 (t, 3H, J¼7.1 Hz,
3
DMAD
2
MeO2C
CO2Me
O
CH ), 2.95 (d, 1H, J¼18.4 Hz, HCH–CO), 3.07 (d, 1H,
3
2
3
13
J¼18.4 Hz, HCH–CO), 4.19 (q, 2H, J¼7.0 Hz, CH );
C
2
NMR (75 MHz, CDCl ): d¼13.8 (CH ), 55.0 (CO–CH ),
3
3
2
NEt2
6
1
1
1.6 (OCH ), 80.8 (COH), 124.5 (2CH ), 127.7 (CH ),
2 Ph Ph
Ph
Ph
(65%)
28.3 (2CH ), 128.6 (2CH ), 128.8 (2CH ), 130.4 (CH ),
Ph
Ph
Ph
Ph
7
31.2, 134.2, 142.5, 163.8, 173.9, 199.9 (C); IR (KBr):
ꢀ
Scheme 2. Synthesis of phthalate 7, (a): (1) 2.3 LDA, THF, 0 C, 1 h; (2) 2a,
ꢀ
~n ¼3463 (s), 3062 (w), 2979 (m), 1737 (s), 1712 (s), 1618
ꢁ
78/20 C, 12 h, (3) addition of SiO
2
, THF, reflux, 17 h and (b): PTSA
(
1
m), 1447 (m), 1461 (m), 1373 (m), 1336 (s), 1211 (s),
102 (m), 772 (m) cm ; MS (EI, 70 eV): m/z (%): 322
ꢀ
(
5 mol %), toluene, 100 C, 10 h.
ꢁ1
+
(
M , 59), 276 (100), 105 (59); elemental analysis: calcd
%) for C H O (322.36): C 74.52, H 5.63; found: C
(
74.43, H 5.36.
2
0 18 4
3
. Experimental section
3
.1. General procedure for the synthesis of functional-
3.1.3. Isopropyl 3-hydroxy-5-oxo-2,3-diphenylcyclopent-
1-ene-1-carboxylate (3c). Starting with isopropyl aceto-
acetate (1.14 mL, 7.84 mmol, 1.1 equiv), diisopropylamine
ized 4-hydroxycyclopent-2-en-1-one-2-carboxylates
a–i and 6
3
(2.51 mL, 17.82 mmol, 2.5 equiv), n-butyllithium (7.13 mL,
17.82 mmol, 2.5 equiv) and benzil (1.50 g, 7.13 mmol), 3c
ꢁ
1
A THF solution (2.5 mL mmol of LDA) of diisopropyl-
amine (2.5 equiv) and n-butyllithium (2.5 equiv, solution
was isolated by chromatography (heptane/ethyl acetate) as
a yellow solid (0.97 g, 41%); mp 110–111 C. Besides,
ꢀ
bonyl compound was added (1.1 equiv) and the mixture was
ꢀ
a small amount of 5 (10 mg) was isolated. Reaction time:
in n-hexane) was stirred at 0 C for 30 min. The 1,3-dicar-
1
stirred for 1 h. To the solution was added the 1,2-diketone
1.0 equiv) at ꢁ78 C. The solution was stirred for 1 h and
20 h. H NMR (250 MHz, CDCl ): d¼1.10 (d, 3H,
3
ꢀ
was then slowly warmed to 20 C with stirring. To the solu-
(
J¼6.7 Hz, CH ), 1.16 (d, 3H, J¼6.7 Hz, CH ), 2.98 (d,
3
3
ꢀ
1H, J¼18 Hz, HCH–CO), 3.10 (d, 1H, J¼18 Hz, HCH–
CO), 5.11 (sept, 1H, J¼6.7 Hz, OCH), 5.30 (s, 1H, OH),
ꢁ
1
tion was added silica gel (0.5 g mmol of 1,2-diketone) and
the mixture was heated to reflux (TLC control). After cool-
ing of the mixture to 20 C, hydrochloric acid (5 mL, 10%),
a saturated aqueous solution of sodium chloride (10 mL),
and diethyl ether (50 mL) were added. The organic and
aqueous layers were separated and the latter was repeatedly
1
3
7.10–7.24 (m, 10H, Ph); C NMR (75 MHz, CDCl ):
3
ꢀ
d¼21.2, 21.4 (CH ), 55.0 (CH ), 69.5 (CH), 80.7 (COH),
3
2
124.5 (2CH ), 127.7 (CH ), 128.2 (2CH ), 128.6
Ph Ph Ph
(2CH ), 128.8 (2CH ), 130.2 (CH ), 131.2, 134.3,
Ph
Ph
Ph
142.5, 163.4, 173.5, 199.8 (C); IR (KBr): ~n ¼3373 (w),

M. Sher et al. / Tetrahedron 63 (2007) 4080–4086
4083
2
1
983 (m), 1718 (s), 1679 (s), 1610 (s), 1450 (m), 1371 (s),
323 (s), 1228 (m), 1095 (s), 1005 (s), 773 (m), 510
(2.44 mL, 17.31 mmol, 2.5 equiv), n-butyllithium (6.92 mL,
17.31 mmol, 2.5 equiv) and 4,4-dimethylbenzil (1.50 g,
6.29 mmol), 3f was isolated by chromatography (heptane/
ethyl acetate) as a slightly yellow solid (1.20 g, 53%). Reac-
ꢁ
1
+
(
2
m) cm ; GC–MS (EI, 70 eV): m/z (%): 336.2 (M , 24),
76.1 (100), 129.1 (33), 105.1 (76), 77.1 (26); HRMS (EI):
calcd for C H O [M] : 336.135023; found: 336.13561.
+
ꢀ
1
tion time: 22 h; mp 118–119 C. H NMR (400 MHz,
2
1 20 4
3
CDCl ): d¼1.16 (d, 3H, J¼7.6 Hz, CH ), 1.20 (d, 3H,
3
3
3
Compound 5: was isolated as a side-product during the
synthesis of 3c. H NMR (300 MHz, CDCl ): d¼1.12 (d,
J¼6.2 Hz, CH ), 2.29 (s, 3H, CH ), 2.33 (s, 3H, CH ),
3
3
3
1
2
2
2.92 (d, 1H, J¼18.4 Hz, HCH–CO), 3.04 (d, 1H, J¼
3
3
3
3
H, J¼6.2 Hz, CH ), 1.14 (d, 3H, J¼6.2 Hz, CH ), 2.11
18.4 Hz, HCH–CO), 5.11–5.18 (m, 1H, OCH), 7.05 (d, 2H,
J¼7.7 Hz, ArH), 7.12 (d, 2H, J¼8.3 Hz, ArH), 7.15 (d,
3
3
3
3
(
(
(
s, 1H, OH), 2.75 (s, 1H, CH), 4.37 (s, 1H, OH), 5.11
sept, 1H, J¼6.2 Hz, CH), 7.29–7.52 (m, 20H, Ph); MS
3
3
3
13
2H, J¼8.0 Hz, ArH), 7.29 (d, 2H, J¼8.3 Hz, ArH);
C
+
CI): 547.3 ([M+1] ); elemental analysis: calcd (%) for
NMR (100 MHz, CDCl ): d¼21.1, 21.44, 21.48, 21.6 (CH ),
3
3
C H O (546.619): C 76.90, H 5.54; found: C 76.81, H
6
55.3 (CH ), 69.4 (CH), 80.7 (COH), 124.4 (2CH ), 128.3
2 Ar
3
5
30
5
.49.
(C), 128.8 (2CH ), 129.0 (2CH ), 129.5 (2CH ), 134.1,
Ar Ar Ar
137.3, 140.0, 140.9, 163.7, 172.9, 199.9 (C); IR (KBr):
3.1.4. Ethyl 4-ethyl-3-hydroxy-5-oxo-2,3-diphenylcyclo-
pent-1-ene-1-carboxylate (3d). Starting with ethyl 3-oxohex-
anoate (1.68 mL, 10.46 mmol, 1.1 equiv), diisopropylamine
(3.35 mL, 23.77 mmol, 2.5 equiv), n-butyllithium (9.51 mL,
~n ¼3428 (w), 2978 (m), 1727 (s), 1693 (s), 1601 (s), 1512
ꢁ1
(m), 1326 (s), 1224 (s), 1100 (s) cm ; GC–MS (EI,
70 eV): m/z (%): 364.2 (M , 36), 304.1 (98), 236.1 (35),
+
206.1 (48), 119.1 (100), 91.1 (39); elemental analysis: calcd
(%) for C H O (364.44): C 75.80, H 6.63; found: C 75.74,
H 6.74.
23.77 mmol, 2.5 equiv) and benzil (2.00 g, 9.51 mmol), 3d
2
3 24 4
was isolated by chromatography (heptane/ethyl acetate) as
a colourless solid (1.82 g, 55%). Reaction time: 24 h; mp
ꢀ
1
1
04–105 C. H NMR (250 MHz, CDCl ): d¼1.01 (t, 3H,
3.1.7. Methyl 3-hydroxy-5-oxo-2,3-di(p-methoxyphenyl)-
cyclopent-1-ene-1-carboxylate (3g). Starting with methyl
acetoacetate (0.87 mL, 8.13 mmol, 1.1 equiv), diisopropyl-
amine (2.60 mL, 18.47 mmol, 2.5 equiv), n-butyllithium
(7.38 mL, 18.47 mmol, 2.5 equiv) and 4,4-dimethoxybenzil
(2.00 g, 7.39 mmol), 3g was isolated by chromatography
(heptane/ethyl acetate) as a slightly yellow solid (0.85 g,
3
3
3
J¼8.2 Hz, CH ), 1.18 (t, 3H, J¼7.3 Hz, CH ), 1.81 (m,
3
3
3
2
H, CH ), 2.68 (t, 1H, J¼7.9 Hz, CH), 4.25 (q, 2H,
2
3
13
J¼6.1 Hz, OCH ), 7.22–7.27 (m, 10H, Ph); C NMR
2
(
(
75 MHz, CDCl ): d¼12.9, 14.5 (CH ), 19.8 (CH ), 61.9
3
3
2
CH ), 64.2 (CH), 84.9 (COH), 126.0 (2CH ), 128.5
2 Ph
(CH ), 128.7 (2CH ), 129.1 (2CH ), 129.2 (2CH ),
Ph Ph Ar Ph
ꢀ
1
130.8 (CH ), 131.4, 134.0, 143.8, 164.6, 173.1, 201.1 (C);
Ph
32%). Reaction time: 20 h; mp 50–52 C. H NMR
IR (KBr): ~n ¼3390 (w), 2978 (m), 1719 (s), 1687 (s), 1629
(250 MHz, CDCl ): d¼2.91 (d, 1H, J¼18 Hz, HCH–CO),
3
(
m), 1447 (s), 1373 (s), 1341 (s), 1247 (s), 1183 (m), 1019
3.06 (d, 1H, J¼18 Hz, HCH–CO), 3.77 (s, 3H, OCH ),
3
ꢁ
1
(
3
s), 963 (m), 699 (s) cm ; GC–MS (EI, 70 eV): m/z (%):
3.80 (s, 3H, OCH ), 3.81 (s, 3H, OCH ), 6.78 (d, 2H,
3
3
+
50.2, (M , 7), 321.1 (31), 304.1 (100), 275.1 (38), 129.1
J¼8.8 Hz, ArH), 6.88 (d, 2H, J¼9.1 Hz, ArH), 7.24 (d,
1
3
(
[
24), 105.1 (54), 77 (23); HRMS (EI): calcd for C H O
2
M] : 350.150583; found: 350.15126.
2H, J¼8.2 Hz, ArH), 7.34 (d, 2H, J¼9.1 Hz, ArH);
C
2 22 4
+
NMR (62 MHz, CDCl ): d¼52.4 (OCH ), 55.2 (2C,
3
3
OCH ), 55.5 (CH –CO), 80.6 (COH), 114.0 (2CH ),
Ar
3
2
3
.1.5. Methyl 3-hydroxy-5-oxo-2,3-di(p-methylphenyl)-
114.2 (2CH ), 123.2 (C), 125.6 (2CH ), 131.1, 132.1
Ar Ar
cyclopent-1-ene-1-carboxylate (3e). Starting with methyl
acetoacetate (0.74 mL, 6.92 mmol, 1.1 equiv), diisopropyl-
amine (2.21 mL, 15.72 mmol, 2.5 equiv), n-butyllithium
(CH ) (2CH ), 135.3, 158.6, 161.6, 164.9, 173.1, 199.5
Ar Ar
(C); IR (KBr): ~n ¼3451 (w), 2839 (m), 1735 (s), 1603 (s),
ꢁ
1
1437 (m), 1137 (s), 1029 (s), 835 (s), 779 (m) cm ; MS
(EI, 70 eV): m/z (%): 368.1 (M , 22), 336.1 (27), 219.0
+
(
(
(
6.29 mL, 15.72 mmol, 2.5 equiv) and 4,4-dimethylbenzil
1.50 g, 6.29 mmol), 3e was isolated by chromatography
heptane/ethyl acetate) as a slightly yellow solid (0.75 g,
(21), 152.0 (78), 135 (100), 77 (29); HRMS (EI): calcd for
C H O [M] : 368.125102; found: 368.12544.
+
2
1 20 6
ꢀ
1
3
6%). Reaction time: 20 h; mp 41–49 C. H NMR
(
400 MHz, CDCl ): d¼2.30 (s, 3H, CH ), 2.34 (s, 3H,
3.1.8. Isopropyl 3-hydroxy-5-oxo-2,3-di(p-methoxyphenyl)-
cyclopent-1-ene-1-carboxylate (3h). Starting with isopropyl
acetoacetate (1.18 mL, 8.13 mmol, 1.1 equiv), diisopropyl-
amine (2.60 mL, 18.47 mmol, 2.5 equiv), n-butyllithium
(7.38 mL, 18.47 mmol, 2.5 equiv) and 4,4-dimethoxybenzil
(2.00 g, 7.39 mmol), 3h was isolated by chromatography
(heptane/ethyl acetate) as a slightly yellow solid (1.36 g,
3
3
2
CH ), 2.94 (d, 1H, J¼18 Hz, HCH–CO), 3.07 (d, 1H,
3
2
J¼18 Hz, HCH–CO), 3.78 (s, 3H, OCH ), 7.07 (d, 2H,
3
3
3
J¼8.5 Hz, ArH), 7.10 (d, 2H, J¼8.5 Hz, ArH), 7.17 (d,
3
3
13
2
H, J¼8.0 Hz, ArH), 7.30 (d, 2H, J¼8.2 Hz, ArH);
C
NMR (100 MHz, CDCl ): d¼21.0, 21.4 (CH ), 52.5
3
3
(
OCH ), 55.3 (OCH ), 80.8 (COH), 124.3 (2CH ), 128.1
3 2 Ar
ꢀ
1
(
C), 128.8 (2CH ), 129.3 (2CH ), 129.6 (2CH ), 133.4,
Ar
47%). Reaction time: 20 h; mp 117–118 C. H NMR
Ar
Ar
3
1
37.6, 139.9, 141.3, 164.5, 173.9, 199.6 (C); IR (KBr):
(400 MHz, CDCl ): d¼1.13 (d, 3H, J¼6.2 Hz, CH ), 1.17
3
3
3
2
~
n¼1739 (s), 1608 (s), 1511 (m), 1435 (m), 1341 (s), 1216
(d, J¼6.2 Hz, 3H, CH ), 2.82 (d, 1H, J¼18.4 Hz, HCH–
3
ꢁ
1
2
(
(
(
(
s), 1015 (m), 820 (s) cm ; MS (EI, 70 eV): m/z (%): 336
M , 44), 304 (98), 236 (37), 206 (48), 143 (40), 119
100), 91 (38); elemental analysis: calcd (%) for C H O
1 20 4
CO), 2.95 (d, 1H, J¼18.4 Hz, HCH–CO), 3.68 (s, 3H,
+
OCH ), 3.71 (s, 3H, OCH ), 5.07–5.14 (m, 1H), 6.68 (d, 2H,
3
3
3
3
J¼9.0 Hz, ArH), 6.79 (d, 2H, J¼8.9 Hz, ArH), 7.19 (d, 2H,
2
3
3
13
360.387): C 74.94, H 5.99; found: C 74.56, H 6.08.
J¼9.0 Hz, ArH), 7.26 (d, 2H, J¼8.9 Hz, ArH); C NMR
100 MHz, CDCl ): d¼21.4, 21.6 (CH ), 55.2, 55.3 (OCH ),
(
3
3
3
3.1.6. Isopropyl 3-hydroxy-5-oxo-2,3-di(p-methylphenyl)-
cyclopent-1-ene-1-carboxylate (3f). Starting with isopropyl
acetoacetate (1.0 mL, 6.92 mmol, 1.1 equiv), diisopropylamine
55.4 (CH ), 69.4 (OCH), 80.5 (COH), 113.8 (2CH ), 114.1
2 Ar
(2CH ), 123.4 (C), 125.7 (2CH ), 131.19 (2CH ), 133.2,
Ar Ar Ar
135.3, 158.9, 161.4, 164.2, 171.8, 199.8 (C); IR (KBr):

4084
M. Sher et al. / Tetrahedron 63 (2007) 4080–4086
~
1
3
n¼3431 (w), 2984 (m), 1740 (s), 1724 (s), 1516 (m), 1264 (s),
was concentrated in vacuo. The residue was purified by
chromatography (silica gel, EtOAc and heptane).
ꢁ
1
242 (s), 1108 (s), 1063 (m), 817 (s), 788 (m) cm ; MS (CI):
+
97 [(M+1) ]; elemental analysis: calcd (%) for C H O
24
23
6
(
396.439): C 69.68, H 6.10; found: C 59.56, H 6.29.
3.2.1. 1,2,3-Trimethyl-4,5-diphenylbenzene-1,2,3-tricar-
boxylate (4a). Starting with 3a (500 mg, 1.62 mmol), DMAD
(1.60 mL, 12.96 mmol) and PTSA (12 mg, 5 mol %), 4a was
isolated by chromatography (heptane/ethyl acetate) as a yellow
3.1.9. Ethyl 3-hydroxy-5-oxo-2,3-di(p-bromophenyl)cyclo-
pent-1-ene-1-carboxylate (3i). Starting with ethyl aceto-
acetate (583 mg, 4.48 mmol, 1.1 equiv), diisopropylamine
(1.43 mL, 10.2 mmol, 2.5 equiv), n-butyllithium (4.1 mL,
ꢀ
1
solid (302 mg, 46%); mp 143–144 C. Reflux time: 8 h. H
NMR (250 MHz, CDCl ): d¼3.48 (s, 3H, OCH ), 3.92 (s,
3
3
1
0.2 mmol, 2.5 equiv) and 4,4-dibromobenzil (1.50 g,
3H, OCH ), 3.93 (s, 3H, OCH ), 7.0–7.21 (m, 10H, Ph), 8.03
3 3
1
3
4.1 mmol), 3i was isolated by chromatography (heptane/ethyl
acetate) as a slightly yellow solid (810 mg, 42%). Reaction
time: 24 h; mp 139–149 C. H NMR (250 MHz, CDCl ):
3
(s, 1H, ArH); C NMR (75 MHz, CDCl ): d¼50.8, 50.9,
3
51.0 (OCH ), 125.9, 126.0 (CH ), 126.1 (2CH ), 126.6
3
Ph
Ph
ꢀ
1
(2CH ), 126.7 (2CH ), 127.6 (2CH ), 130.1, 130.8 (C),
Ph Ph Ph
132.3 (CH ), 135.4, 137.0, 139.1, 140.6, 141.7, 163.9, 165.8,
Ph
3
2
d¼1.20 (t, 3H, J¼7.6 Hz, CH ), 2.97 (d, 1H, J¼18 Hz,
3
2
HCH–CO), 3.07 (d, 1H, J¼18 Hz, HCH–CO), 4.25 (q, 2H,
166.9 (C); IR (KBr): ~n ¼1743 (s), 1728 (s), 1588 (m), 1429
3
3
J¼7.6 Hz, CH ), 7.13 (d, 2H, J¼9.1 Hz, ArH), 7.26 (d,
(s), 1299 (s), 1244 (s), 1156 (m), 1008 (s), 765 (m), 703
(s) cm ; MS (EI, 70 eV): m/z (%): 404.1 (M , 68), 373.1
2
3
3
ꢁ1
+
2
H, J¼8.5 Hz, ArH), 7.41 (d, 2H, J¼8.5 Hz, ArH), 7.48
3
13
(
d, 2H, J¼8.8 Hz, ArH); C NMR (75 MHz, CDCl ):
(100), 226.0 (11), 105 (22); HRMS (EI): calcd for C H O
24 20 6
3
+
d¼14.3 (CH ), 55.3 (CH ), 62.4 (OCH ), 80.9 (COH),
[M] : 404.125328; found: 404.12544.
3
2
2
1
22.4, 125.8 (C), 126.8 (2CH ), 130.3 (C), 130.6 (2CH ),
Ar Ar
1
32.1 (2CH ), 132.4 (2CH ), 134.9, 141.7, 164.1, 199.8
Ar
3.2.2. 3-Ethyl-1,2-dimethyl-4,5-diphenylbenzene-1,2,3-
tricarboxylate (4b). Starting with 3b (400 mg, 1.24 mmol),
DMAD (1.21 mL, 11.84 mmol, 8 equiv) and PTSA
(5 mol %), 4b was isolated by chromatography (heptane/ethyl
Ar
(
C); IR (KBr): ~n ¼3481 (w), 1744 (s), 1486 (m), 1336 (s),
ꢁ1
1
7
4
217 (m), 1072 (s), 1010 (s), 825 (m) cm ; GC–MS (EI,
0 eV): m/z (%): 482 (M , Br, 10), 479.9 (M , Br, 17),
33.9 (57), 281.1 (42), 207 (100), 185 (49); elemental analysis:
+
81
+ 79
ꢀ
1
acetate) as a yellow solid (293 mg, 46%); mp 135–137 C. H
NMR (300 MHz, CDCl ): d¼0.88 (t, 3H, J¼7.1 Hz), 3.92
3
calcd (%) for C H O Br (479.95): C 50.01, H 3.36; found:
2
C 49.67, H 3.40.
0
16
4
2
3
3
(s, 6H, OCH ), 3.95 (q, 2H, J¼7.1 Hz), 7.01–7.21 (m,
3
1
3
1
0H, Ph), 8.03 (s, 1H, ArH); C NMR (75 MHz, CDCl ):
3
3
.1.10. 3-Hydroxy-5-oxo-2,3-diphenylcyclopent-1-ene-1-
d¼13.3 (CH ), 52.7, 52.8 (OCH ), 61.6 (OCH ), 127.2,
3
3
2
N,N-diethylacetoacetamide (6). Starting with N,N-diethyl-
acetamide (0.82 mL, 5.22 mmol, 1.1 equiv), diisopropyl-
amine (1.61 mL, 11.41 mmol, 2.5 equiv), n-butyllithium
127.5 (CH ), 127.7 (2CH ), 127.8 (2CH ), 128.3 (C),
Ph Ph Ph
129.4 (2CH ), 125.5 (2CH ), 132.1 (CH ), 132.6, 134.3,
Ph
Ph
Ph
137.4, 138.9, 142.5, 143.5, 165.7, 167.3, 167.8 (C); IR
(KBr): ~n ¼1745 (s), 1726 (s), 1429 (m), 1337 (m), 1243 (s),
(
4
4.36 mL, 11.4 mmol, 2.5 equiv) and benzil (1.00 g,
.75 mmol), 6 was isolated by chromatography (heptane/
ethyl acetate) as a slightly yellow solid (725 mg, 43%).
ꢁ
1
1161 (m), 1022 (m), 765 (m), 703 (s) cm ; MS (EI,
70 eV): m/z (%): 418 (M , 100), 373 (73), 327 (63), 306
+
ꢀ
1
Reaction time: 17 h; mp 117–118 C. H NMR (250 MHz,
(26), 226 (38), 133 (59), 57 (33); elemental analysis: calcd
(%) for C H O (418.445): C 71.75, H 5.29; found: C
71.64, H 5.04.
3
CDCl ): d¼1.00 (t, 3H, J¼6.4 Hz, CH ), 1.16 (t, 3H,
3
3
25 22 6
3
J¼7.3 Hz, CH ), 3.11–3.50 (m, 2H), 3.55–3.85 (m, 2H),
3
3
.85 (s, 1H, CH–C]O), 6.77 (s, 1H, CH]C), 7.25–7.68
1
3
(
m, 10H, Ph); C NMR (62 MHz, CDCl ): d¼12.9, 14.3
3.2.3. 3-Isopropyl-1,2-dimethyl-4,5-diphenylbenzene-
1,2,3-tricarboxylate (4c). Starting with 3c (500 mg,
1.48 mmol), DMAD (1.23 mL, 11.84 mmol) and PTSA
(5 mol %), 4c was isolated by chromatography (heptane/
ethyl acetate) as a yellow solid (293 mg, 46%). Reflux
3
(
CH ), 41.3, 42.7 (CH ), 63.4 (CH), 82.3 (COH), 124.6
3
2
(
2CH ), 127.5 (CH ), 127.8 (CH ), 128.4 (2CH ),
Ph Ph Ph Ph
1
1
2
1
7
1
28.8 (2CH ), 129.7 (2CH ), 130.9 (CH ), 131.2 (CH),
Ph Ph Ph
44.2, 167.7, 176.6, 199.7 (C); IR (KBr): ~n ¼3399 (w),
ꢀ
1
978 (m), 1691 (s), 1624 (s), 1571 (m), 1449 (s), 1309 (s),
223 (s), 1339 (m), 772 (s), 6004 (s) cm ; MS (EI,
time: 12 h; mp 161–162 C. H NMR (250 MHz, CDCl ):
3
ꢁ
1
3
d¼0.91 (d, 6H, J¼5.8 Hz), 3.92 (s, 3H, OCH ), 3.93 (s,
3
+
3
0 eV): m/z (%): 349.2 (M , 33), 331.1 (23), 249.1 (100),
05.0 (43), 72.1 (26); HRMS (EI): calcd for C H O N
3H, OCH ), 4.83 (sept, 1H, J¼7.6 Hz), 6.99–7.20 (m,
3
1
3
10H, Ph), 8.02 (s, 1H, ArH); C NMR (62 MHz, CDCl ):
3
2
2
23
3
1
+
[
M] : 349.166663; found: 349.16725.
d¼21.1 (2C, CH ), 52.7, 52.8, (OCH ), 69.5 (CH), 127.2
3
3
(2CH ), 127.5 (CH ), 127.7 (C), 127.8 (2CH ), 128.3
Ph Ph Ph
3
.2. General procedure for the cyclization of function-
(CH ), 129.4 (2CH ), 129.7 (2CH ), 129.9 (C), 132.5
Ph Ph Ph
alized 4-hydroxycyclopent-2-en-1-ones with dimethyl
acetylenedicarboxylate (DMAD)
(CH ), 134.5, 137.6, 139.1, 142.1, 143.8, 165.7, 167.0,
Ph
168.0 (C); IR (KBr): ~n ¼1740 (s), 1723 (s), 1550 (m), 1499
(m), 1429 (s), 1326 (s), 1241 (s), 1109 (s), 1000 (s), 910
(m), 700 (s), 552 (m) cm ; GC–MS (EI, 70 eV): m/z (%):
ꢁ1
To a toluene solution (25 mL) of the 4-hydroxycyclopent-2-
en-1-one (1.0 equiv) were added dimethyl acetylenedicar-
boxylate (DMAD, 8.0 equiv) and p-toluenesulfonic acid
+
432.2 (M , 100), 373.1 (54), 359.1 (28), 327.1 (55), 256.1
(35), 226.1 (62); elemental analysis: calcd (%) for
C H O (432.47): C 72.20, H 5.59; found: C 72.21, H 5.56.
(PTSA, 5 mol %). The mixture was heated at reflux (TLC
control). After cooling of the reaction mixture to 20 C, a sat-
2
6 24 6
ꢀ
urated aqueous solution of NaHCO (10 mL) was added.
Compound 4d: starting with 3d (400 mg, 1.14 mmol),
DMAD (0.95 mL, 9.13 mmol) and PTSA (5%), 4d was iso-
lated by chromatography (heptane/ethyl acetate) as a yellow
3
The organic and aqueous layers were separated and the latter
was extracted with diethyl ether (3ꢂ20 mL). The combined
organic layers were dried (Na SO ), filtered and the filtrate
ꢀ
solid (165 mg, 33%); mp 51–53 C. Reflux time: 11 h.
2
4

M. Sher et al. / Tetrahedron 63 (2007) 4080–4086
4085
1
ꢀ
OCH ), 3.76 (s, 3H, OCH ), 3.77 (s, 3H, OCH ), 3.92 (s,
1
A small amount of impurity could not be separated. H NMR
143–144 C. H NMR (250 MHz, CDCl ): d¼3.52 (s, 3H,
3
3
(
(
250 MHz, CDCl ): d¼0.92 (t, 3H, J¼7.6 Hz, CH ), 1.17
3
3
3
3
3
3
3
3
t, 3H, J¼7.3 Hz, CH ), 2.53 (q, 2H, J¼6.4 Hz, CH ),
6H, OCH ), 6.72 (d, 2H, J¼9.1 Hz, ArH), 6.74 (d, 2H,
3
2
3
3
3
3
.86 (s, 3H, OCH ), 3.92 (s, 3H, OCH ), 4.24 (q, 2H,
3
J¼8.8 Hz, ArH), 6.95 (d, 2H, J¼8.5 Hz, ArH), 6.96 (d,
3
3
13
3
13
J¼6.5 Hz, OCH ), 6.95–7.18 (m, 10H, Ph); C NMR
2H, J¼8.5 Hz, ArH), 7.98 (s, 1H, ArH); C NMR
(75 MHz, CDCl ): d¼52.4, 52.7, 52.9, 55.0, 55.1 (OCH ),
2
(
62 MHz, CDCl ): d¼12.2, 13.9 (CH ), 19.1 (CH ), 52.6,
3
3
2
3
3
5
1
1
1
1
1
2.9 (OCH ), 61.5 (OCH ), 125.5 (2CH ), 126.9 (CH ),
Ph
113.3 (2CH ), 113.4 (2CH ), 128.3, 129.6 (C), 130.7
Ar Ar
3
2
Ph
27.5 (C), 128.0 (2CH ), 128.8 (2CH ), 129.6 (2CH ),
Ph
29.7 (C), 130.4 (CH ), 131.0, 133.3, 133.7, 137.6, 139.4,
Ph
(2CH ), 131.4 (2C), 132.6 (CH ), 134.4, 142.0, 143.3,
Ar Ar
Ph
Ph
158.8, 158.9, 165.9, 167.8, 168.0 (C); IR (KBr): ~n ¼1745
41.8, 163.8, 166.5, 171.8 (C); IR (KBr): ~n ¼2950 (m),
(s), 1608 (s), 1575 (m), 1516 (s), 1458 (m), 1435 (s), 1339
(s), 1248 (s), 1067 (m), 843 (m) cm ; GC–MS (EI,
ꢁ1
797 (s), 1646 (m), 1541 (s), 1331 (s), 1282 (w), 1232 (s),
171 (m), 1062 (s), 966 (m), 778 (m), 698 (s) cm ; GC–
ꢁ
1
+
70 eV): m/z (%): 464.2, (M , 100), 433.1 (16), 401.1 (11);
elemental analysis: calcd (%) for C H O (464.47): C
67.23, H 5.21; found: C 66.89, H 5.20.
+
MS (EI, 70 eV): m/z (%): 446.2 (M , 7), 400.1 (46), 353.1
100), 239.1 (28).
2
6 24 8
(
3
1
1
.2.4. 1,2,3-Trimethyl-4,5-di(p-methylphenyl)-benzene-
,2,3-tricarboxylate (4e). Starting with 3e (400 mg,
.18 mmol), DMAD (1.16 mL, 9.51 mmol, 8 equiv) and
3.2.7. 3-Isopropyl-1,2-dimethyl-4,5-di(p-methoxy-
phenyl)-benzene-1,2,3-tricarboxylate 4h. Starting with
3h (500 mg, 1.26 mmol), DMAD (1.23 mL, 10.08 mmol,
8 equiv) and PTSA (5%), 4h was isolated by chromato-
graphy (heptane/ethyl acetate) as a yellow solid (290 mg,
PTSA (12 mg, 5 mol %), 4e was isolated by chromatography
heptane/ethyl acetate) as a yellow solid (340 mg, 86%);
(
ꢀ
1
ꢀ
1
mp 167–169 C. H NMR (400 MHz, CDCl ): d¼2.27
46%); mp 130–132 C. H NMR (400 MHz, CDCl3):
d¼0.95 (d, 6H, J¼6.2 Hz, CH ), 3.74 (s, 6H, OCH ), 3.88
3
3
(
s, 3H, CH ), 2.28 (s, 3H, CH ), 3.49 (s, 3H, OCH ), 3.90
3
3
3
3
3
(
s, 3H, OCH ), 3.91 (s, 3H, OCH ), 6.90 (d, 2H,
3
(s, 3H, OCH ), 3.89 (s, 3H, OCH ), 4.89 (sept, 1H,
3 3
3
3
3
3
3
J¼8.2 Hz, ArH), 6.91 (d, 2H, J¼8.2 Hz, ArH), 6.98
J¼6.2 Hz, OCH), 6.70 (d, 2H, J¼6.4 Hz, ArH), 6.72 (d,
3
3
3
3
(
7
2
d, 2H, J¼7.8 Hz, ArH), 6.99 (d, 2H, J¼7.8 Hz, ArH),
2H, J¼6.3 Hz, ArH), 6.92 (d, 2H, J¼8.8 Hz, ArH), 6.95
1
3
3
13
.24 (s, 1H, Ar); C NMR (100 MHz, CDCl ): d¼21.0,
(d, 2H, J¼8.8 Hz, ArH), 7.24 (s, 1H, ArH); C NMR
(100 MHz, CDCl ): d¼20.2 (2CH ), 51.7, 51.8, 54.1, 54.2
3
1.2 (CH ), 52.3, 52.7, 52.9 (OCH ), 128.3 (C), 128.5
3
3
3
3
(
(
2CH ), 128.6 (2CH ), 129.4 (4CH ), 131.6 (C), 132.7
Ar
CH ), 134.3, 134.4, 136.1, 137.0, 137.2, 142.5, 143.6,
Ar
(OCH ), 68.3 (CH),112.3 (2CH ), 112.4 (2CH ), 127.1,
3 Ar Ar
Ar
Ar
128.9, 129.9, 130.4 (C), 130.5 (2CH ), 131.3 (2CH ),
Ar Ar
1
65.9, 167.9, 167.0; IR (KBr): ~n ¼1738 (s), 1515 (m), 1433
133.9 (CH ), 140.8, 142.3, 157.7, 158.0, 164.9, 166.0,
Ar
(
s), 1297 (s), 1265 (s), 1222 (s), 1159 (m), 1065 (m),
166.9 (C); IR (KBr): ~n ¼1741 (s), 1727 (s), 1608 (s), 1516
ꢁ1
1
(
000 (s), 779 (m) cm ; MS (EI, 70 eV): m/z (%): 432
M , 100), 401 (82), 385 (21); elemental analysis: calcd
(s), 1461 (m), 1351 (m), 1251 (m), 1160 (s), 1065 (s), 833
(m) cm ; MS (EI, 70 eV): m/z (%): 492 (M , 100), 450
+
ꢁ1
+
(
7
%) for C H O (432.46): C 72.21, H 5.59; found: C
2
2.25, H 6.00.
(20), 418 (25), 387 (19); HRMS (EI): calcd for C H O
28 28 8
[M] : 492.177507; found: 492.17787.
6
24
6
+
3
.2.5. 3-Isopropyl-1,2-dimethyl-4,5-di(p-methylphenyl)-
3.2.8. 3-Ethyl-1,2-dimethyl-4,5-di(p-bromophenyl)-ben-
zene-1,2,3-tricarboxylate (4i). Starting with 3i (400 mg,
0.83 mmol), DMAD (0.81 mL, 6.66 mmol, 8 equiv) and
PTSA (5 mol %), 4i was isolated by chromatography (hep-
tane/ethyl acetate) as a yellow solid (325 mg, 68%); mp
benzene-1,2,3-tricarboxylate (4f). Starting with 3f (500 mg,
.37 mmol), DMAD (1.34 mL, 10.97 mmol, 8 equiv) and
PTSA (5 mol %), 4f was isolated by chromatography (hep-
1
tane/ethyl acetate) as a yellow solid (250 mg, 40%); mp
ꢀ
1
ꢀ
1
1
55–157 C. H NMR (400 MHz, CDCl ): d¼0.93 (d, 6H,
171–173 C. H NMR (400 MHz, CDCl ): d¼0.96 (t, 3H,
3
3
3
3
J¼6.2 Hz, CH ), 2.27 (s, 6H, CH ), 3.90 (s, 3H, OCH ),
J¼7.1 Hz, CH ), 3.92 (s, 6H, OCH ), 3.99 (q, 2H,
3
3
3
3
3
3
3
3
.91 (s, 3H, OCH ), 4.80–4.87 (m, 1H, OCH), 6.46 (d, 2H,
3
J¼7.1 Hz, OCH CH ), 6.88 (d, 2H, J¼8.4 Hz, ArH),
2
3
3
3
3
3
J¼8.2 Hz, ArH), 6.94 (d, 2H, J¼8.2 Hz, ArH), 6.98
6.92 (d, 2H, J¼8.4 Hz, ArH), 7.35 (d, 2H, J¼8.4 Hz,
13
3
3
3
(
d, 2H, J¼7.8 Hz, ArH), 7.99 (d, 2H, J¼7.8 Hz, ArH),
ArH), 7.36 (d, 2H, J¼8.4 Hz, ArH), 7.98 (s, 1H, ArH);
13
7.98 (s, 1H, Ar); C NMR (100 MHz, CDCl ): d¼20.08
C NMR (100 MHz, CDCl ): d¼13.4 (CH ), 52.8, 52.9
3
3
3
(2C, CH ), 20.09 (CH ), 20.16 (CH ), 51.7 (OCH ), 51.8
3
(OCH ), 61.4 (OCH ), 122.0, 122.2, 128.9 (C), 131.0
3 2
3
3
3
(
OCH ), 68.3 (CH), 127.1, 127.5, 127.6 (C), 128.4 (2CH ),
Ar
(2CH ), 131.1 (2CH ), 131.2 (2CH ), 131.3 (2CH ),
Ar Ar Ar Ar
3
1
28.6 (2CH ), 130.6 (2CH ), 131.5 (2CH ), 133.5
Ar
132.5 (CH ), 132.6, 136.0, 137.5, 141.0, 142.2, 165.4,
Ar
Ar
Ar
(
1
1
CH ), 133.7, 135.2, 135.9, 136.2, 141.3, 142.5, 164.9,
Ar
166.8, 167.5 (C); IR (KBr): ~n ¼2950 (m), 1742 (s), 1493
ꢁ
1
66.0, 166.9 (C); IR (KBr): ~n ¼2980 (m), 1725 (s), 1687 (s),
(m), 1249 (s), 1202 (s), 1073 (m), 835 (m), 701 (m) cm ;
MS (EI, 70 eV): m/z (%): 578.9 (M , Br, 12), 575.9
+
81
598 (s), 1513 (s), 1457 (m), 1327 (m), 1251 (s), 835
ꢁ
1
+
+ 79
(m) cm ; MS (EI, 70 eV): m/z (%): 460.2 (M , 100), 401.1
(M , Br, 100), 530.9 (37), 484.9 (33), 229 (31), 121.1
(36), 91 (29); elemental analysis: calcd (%) for
C H O Br (576.237): C 52.11, H 3.52; found: C 52.16,
(24), 355.1 (35), 239.1 (20), 131 (26), 69 (75); elemental anal-
ysis: calcd (%) for C H O (460.526): C 73.62, H 6.12;
found: C 73.73, H 6.34.
28
28
6
25 20
6
2
H 3.54.
3
1
1
.2.6. 1,2,3-Trimethyl-4,5-di(p-methoxyphenyl)-benzene-
,2,3-tricarboxylate (4g). Starting with 3g (500 mg,
.35 mmol), DMAD (1.13 mL, 10.85 mmol, 8 equiv) and
Compound 7: starting with 6 (200 mg, 0.57 mmol), DMAD
(0.65 mL, 4.58 mmol) and PTSA (5 mol %), 7 was isolated
by chromatography (heptane/ethyl acetate) as a yellow solid
ꢀ
1
PTSA (5 mol %), 4g was isolated by chromatography (hep-
tane/ethyl acetate) as a yellow solid (250 mg, 40%); mp
(165 mg, 65%); mp 143–144 C. Reflux time: 10 h. H NMR
3
(250 MHz, CDCl ): d¼0.68 (t, 3H, J¼7.3 Hz, CH ), 0.84 (t,
3
3

4086
M. Sher et al. / Tetrahedron 63 (2007) 4080–4086
3
3
3
7
(
5
1
H, J¼7.3 Hz, CH ), 2.51–2.65 (1H), 2.90–3.06 (2H),
References and notes
3
.40–3.49 (1H), 3.88 (s, 3H, OCH ), 3.91 (s, 3H, OCH ),
3
.01–7.60 (m, 10H, Ph), 8.02 (s, 1H, ArH); C NMR
3
1
3
1. Modern Arene Chemistry; Astruc, D., Ed.; Wiley-VCH:
Weinheim, 2002.
2. Sankararaman, S. Pericyclic Reactions—A Textbook; Wiley-
VCH: Weinheim, 2005.
62 MHz, CDCl ): d¼11.5, 12.5 (CH ), 37.6, 42.5 (CH ),
3
3
2
2.73, 52.75 (OCH ), 127.2, 127.3 (C), 127.6 (2CH ),
Ph
3
27.9 (CH ), 128.5 (2CH ), 129.6 (2CH ), 130.1
Ph
Ph
Ph
(
1
2CH ), 131.7 (CH ), 131.8 (CH ), 136.6, 137.2, 139.4,
Ph
40.7, 143.2, 166.0, 167.0, 168.1 (C); IR (KBr): ~n ¼2951
3. For a recent application of this reaction, see: Rivera, J. M.;
Martin, T.; Rebek, J. J. Am. Chem. Soc. 2001, 123, 5213.
4. (a) Dilthey, W.; Hurtig, G. Ber. Deutsch. Chem. Ges. 1934, 67,
2004; (b) Dilthey, W.; Schommer, W.; Troesken, O. Ber.
Deutsch. Chem. Ges. 1933, 66, 1627.
5. (a) Allen, C. F. H.; VanAllan, J. J. Org. Chem. 1945, 10, 333; (b)
Herz, W.; Lewis, E. J. Org. Chem. 1958, 23, 1646; (c) Borchardt,
A.; Hardcastle, K.; Gantzel, P.; Siegel, J. S. Tetrahedron Lett.
1993, 34, 273; (d) Becker, H.; King, S. B.; Taniguchi, M.;
Vanhessche, K. P. M.; Sharpless, K. B. J. Org. Chem. 1995,
60, 3940; (e) Ohta, K.; Yamaguchi, N.; Yamamoto, I. J. Mater.
Chem. 1998, 8, 2637.
Ph
Ar
(
1
w), 1731 (s), 1628 (s), 1437 (m), 1267 (s), 1163 (m),
092 (m), 761 (s), 702 (s) cm ; MS (EI, 70 eV): m/z (%):
ꢁ1
+
4
(
45.1 (M , 2), 386.1 (91), 373.0 (100), 342.0 (17), 226.0
33), 72.0 (54); HRMS (EI): calcd for C H O N [M] :
+
2
7 27 5 1
4
45.188455; found: 445.18837.
3
.3. X-ray crystallographic study
Crystallographic data were collected at 173 K with a Bruker
X8Apex diffractometer and CCD area-detector, with the
use of graphite-monochromatized Mo Ka radiation (l
0
u scans. The structures were solved by direct methods
6. Holtz, E.; K €o hler, V.; Appel, B.; Langer, P. Eur. J. Org. Chem.
2005, 532.
˚
.71073 A). The data collection was performed with f and
7. (a) Okano, K.; Mizuhara, Y.; Suemune, H.; Akita, H.; Sakai, K.
Chem. Pharm. Bull. 1988, 36, 1358; (b) Okano, K.; Suemune, H.;
Sakai, K. Chem. Pharm. Bull. 1988, 36, 1385; (c) Suemune, H.;
Miyao, Y.; Sakai, K. Chem. Pharm. Bull. 1989, 37, 2523; (d)
Okano, K.; Suemune, H.; Sakai, K. Chem. Pharm. Bull. 1989, 37,
1995; (e) Okano, K.; Suemune, H.; Sakai, K. Chem. Pharm. Bull.
1990, 38, 532.
8. CCDC-628559 (3b), CCDC-628560 (4c) and CCDC-628561 (5)
contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge at www.ccdc.
cam.ac.uk/conts/retrieving.html (or from the Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge CB2
1EZ, UK; fax: (internet) +44 1223336033; e-mail: deposit@
ccdc.cam.ac.uk).
with use of the Bruker SHELXTL software package and
full-matrix, least-squares refinements on F were performed
2
with the SHELXL-97 program. In all cases, all heavy atoms
were refined anisotropically. The hydrogen atoms were in-
cluded at fixed distances from their host atoms, with fixed
displacement parameters. Figures were drawn with Bruker
XP, all at 50% level for the thermal ellipsoids.
Acknowledgements
Financial support from the Deutsche Forschungsgemein-
schaft is gratefully acknowledged.