Three-component synthesis of polysubstituted benzene derivatives via Diels-Alder reaction of cyclopentadienone acetal with alkyne

Article abstract of DOI:10.1016/j.tet.2005.09.011

An efficient and regioselective synthesis of polysubstituted benzene derivatives was achieved via multicomponent reaction of a substituted cyclopropenone acetal and two alkyne molecules. The synthesis utilizes cyclopentadienone acetal as an intermediate a

Full text of DOI:10.1016/j.tet.2005.09.011

Tetrahedron 61 (2005) 11449–11455
Three-component synthesis of polysubstituted benzene derivatives
via Diels–Alder reaction of cyclopentadienone acetal with alkyne
†
Sota Sato, Hiroyuki Isobe, Takatsugu Tanaka, Tomohiko Ushijima and Eiichi Nakamura
*
Department of Chemistry and ERATO (JST), The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Received 1 July 2005; revised 25 August 2005; accepted 2 September 2005
Available online 5 October 2005
Abstract—An efficient and regioselective synthesis of polysubstituted benzene derivatives was achieved via multicomponent reaction of a
substituted cyclopropenone acetal and two alkyne molecules. The synthesis utilizes cyclopentadienone acetal as an intermediate and enables
regioselective [2C2C2] assembly of the three-components into a benzene ring. A variety of polysubstituted benzene derivatives of synthetic
and structural interest have been synthesized.
q 2005 Published by Elsevier Ltd.
1. Introduction
2. Results and discussion
Polysubstituted benzene is an important class of compounds
in organic chemistry, natural product chemistry, and
materials science. Multicomponent construction of benzene
ring is an intriguing possibility in benzene synthesis. For
instance, a [2C2C2] synthesis has been achieved by tran-
sition metal catalyzed reactions,1–3 and a [4C2] synthesis
either by transition metal catalyzed reactions or by thermal
reactions.1,4,5 These examples largely dealt with intra-
molecular reactions, and regioselective synthesis by inter-
molecular reactions has remained to be a challenge for
synthetic chemists. We herein report an example of regio-
selective [2C2C2] synthesis of polysubstituted benzenes
by a thermal intermolecular reaction (Scheme 1). The
synthesis involves cyclopentadienone acetal (CPDA)6 as a
transient or an isolated intermediate. The stepwise synthesis
with isolated CPDA comprises a [2C2C2] assembly of
three different components into a benzene ring. We have
previously reported an example of the transformation6 and
describe here the scope of the three-component synthesis.
2.1. One-pot three-component synthesis of polysubstituted
benzenederivatives. Thermal reactionofCPAand alkynes
During the investigation of the synthesis of CPDA
derivatives,6 we noticed that a thermal reaction of a
cyclopropenone acetal (CPA 1)7 with an alkyne gives a
small amount of polysubstituted benzene. For instance,
when equimolar amounts of phenyl CPA 1a and dimethyl
acetylene dicarboxylate (DMAD) was heated in toluene for
1 h, we obtained a polysubstituted benzene 4a in 9% yield
along with CPDA 2a in 40% yield (Eq. 1; Table 1, entry 1).
The observation suggested occurrence of three successive
reactions shown in Eq. 1, that is, [3C2] cycloaddition,
Diels–Alder reaction, and cheletropic extrusion of dialkoxy-
carbene (vide infra). The net result is the one-pot assembly
of one molecule of CPA and two molecules of an alkyne
into a polysubstituted benzene in a [2C2C2] manner.
(1)
Scheme 1.
Keywords: Polysubstituted benzene; Three-component [2C2C2] syn-
thesis; Diels–Alder reaction; Cyclopropene; Cyclopentadiene.
*
Corresponding author. Tel./fax: C81 3 5800 6889;
e-mail: nakamura@chem.s.u-tokyo.ac.jp
† PRESTO, JST.
0040–4020/$ - see front matter q 2005 Published by Elsevier Ltd.
doi:10.1016/j.tet.2005.09.011

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S. Sato et al. / Tetrahedron 61 (2005) 11449–11455
Table 1. One-pot three-component synthesis of polysubstituted benzene derivatives by the reaction shown in Eq. 1
Entry
Alkyne (equiv)
Yield of 4 (%)
Substituents of 4
1a
2b
3b
4b
5b
1.0
4.0
4.0
2.0
2.0
9
4a
R1ZPh, R2ZCO2Me, R3ZCO2Me
59
63
76
31
4b
4c
4d
R1Z4-MeOC6H4, R2ZCO2Me, R3ZCO2Me
R1Z1-naphthyl, R2ZCO2Me, R3ZCO2Me
R1ZPh, R2ZPh, R3ZSO2CF3
a CPDA 2a (R1ZPh, R2ZR3ZCO2Me) was obtained in 40% yield.
b CPDA 2 was not obtained.
The new benzene synthesis was found to have considerable
generality as a method to synthesize a variety of poly-
substituted benzene derivatives. Thus, when phenyl CPA
1a, anisyl CPA 1b, or 1-naphthyl CPA 1c was allowed to
react with 2–4 equiv of DMAD or an unsymmetric alkyne,
the corresponding benzene derivatives 4a, 4b, 4c, and 4d
were obtained in 59, 63, 76, and 31% yield, respectively.
as 27.78 at S1–C1–C2–C7 (Fig. 1b) and that of the benzene
ring reaches 12.38 at C1–C2–C3–C4. Nonplanar benzene
rings have been observed rarely and only for symmetric
benzene derivatives.8
2.2. Stepwise three-component synthesis of polysubsti-
tuted benzene derivatives. Thermal Diels–Alder reaction
of CPDA and alkynes
Crystallographic analysis of the highly substituted benzene
4d revealed that the molecule is significantly distorted
owing to steric interactions among substituents (Fig. 1). The
torsion angle between ortho-substituents measures as much
The reaction described above incorporates two identical
alkynes into a benzene ring. Two different alkynes can be
incorporated when CPDA is synthesized first and then
allowed to react with the second alkyne (Eq. 2).9 A variety
of CPDA 2 can be synthesized by the Pd-catalyzed method
that we reported.6 The Diels–Alder reaction of the
substituted CPDA with the second alkyne enables the
assembly of three different components into a benzene ring
in a controlled manner.
(2)
The reaction of CPDA 2a with alkynes proceeded in one-pot
to afford a variety of polysubstituted benzene derivatives in
moderate to high yield (Table 2). CPDA 2a was first
prepared by the Pd-catalyzed [3C2] synthesis6 and then
allowed to react with an equimolar amount of a aryl alkyne
to give the corresponding benzene derivative as a single
regioisomer (Table 2, entry 1 and 2). The reaction with an
enyne proceeded regioselectively and chemoselectively at
the C–C triple bond. The yield of the benzene derivative 7
was not high in the reaction without solvent, but dramatic
improvement to 75% yield was observed when we carried
out the reaction in an alcohol to capture the extruded
dialkoxycarbene (entry 3). The benzene derivative was
obtained as a mixture of regioisomer in the reaction with
propargyl ether (entry 4). A synthetically useful arylboro-
nate 910 was obtained in 68% yield when we used ethynyl
boronate as a dienophile (entry 5).11 The high regio-
selectivity in the reaction with monosubstituted alkynes
results from the selectivity in the Diels–Alder cycloaddition,
and the origin of the selectivity will be the subject of future
theoretical study. The reaction with a disubstituted alkyne
such as tolane was not as efficient as monosubstituted ones,
giving the benzene derivative 10 in 39% yield (entry 6).
Figure 1. X-ray crystallographic structure of disulfonyl benzene 4d. The
key atoms are shown in a ball and stick model. (a) Top view; (b) side view
shown along the C4–C5 bond. Color codes of atoms: C, gray; H, white; O,
red; S, yellow; F, blue.
The use of acetylene (gas) in the present synthesis is difficult,
because the reaction requires high temperature. However, the

S. Sato et al. / Tetrahedron 61 (2005) 11449–11455
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use of its surrogate, norbornadiene, allowed the incorporation
3. Conclusion
of an acetylene unit into a benzene ring.6 Norbornadiene was
first allowed to react with CPDA 2a to obtain the Diels–Alder
adduct 12 in 98% yield. The adduct 12 was then converted to
the benzene derivative 13 in 78% yield by thermolytic
extrusion of dialkoxycarbene and cyclopentadiene (Eq. 3).
Dialkoxycarbene generated by the cheletropic extrusion was
identified by isolation of its dimer, tetraalkoxyethylene 14.
In summary, we have developed a method for the synthesis
of polysubstituted benzene derivatives. The present [2C2C
2] synthesis is highly regioselective and chemoselective
and tolerates a variety of functional groups including a
sulfonyl and a boryl groups. Such synthesis of unsymmetric
polysubstituted benzene derivatives has been rarely
achieved by transition metal catalyzed reactions and will
find applications in the synthesis of polycyclic aromatic
compounds.10,12
(3)
4. Experimental
4.1. General
IR spectra were obtained on an ASI Applied Systems
REACT IR1000 equipped with an attenuated total reflection
Table 2. Stepwise synthesis of polysubstituted benzene derivatives by the reaction of CPDA 2a and alkyne (Eq. 2)
Entry
Alkyne (equiv)
Conditions
Producta
(1.0)
1
Toluene, 100 8C, 110 h
5, 97%
(1.0)
2
PhCl, reflux, 24 h
6, 88%
(35)
3
4
t-BuOH, 150 8C, 21 h
7, 75%b
(2.4)
1,2,4-Cl3C6H3, 150 8C, 8 days
8, 76%
9, 15%
(2.0)
5
PhCl, 120 8C, 42 h
10, 68%
(2.0)
6
Ph2O, reflux, 12 h
11, 39%
a EZCO2Me.
b The reaction in the absence of solvent gave 7 in 22% yield.

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S. Sato et al. / Tetrahedron 61 (2005) 11449–11455
(ATR) instrument. NMR spectra were obtained on JEOL
EX-270, AL-300, ECX-400, ECA-500, and Bruker AV-500
spectrometers. H NMR spectra in CDCl3 were referenced
compound 4c as a viscous liquid in 71% yield (232 mg,
0.532 mmol); H NMR (400 MHz, CDCl3) d 3.33 (s, 3H),
1
1
3.89 (s, 3H!2), 4.00 (s, 3H), 7.31 (dd, JZ1.2, 7.2 Hz, 1H),
7.5 (m, 4H), 7.89 (d, JZ4.4 Hz, 2H), 8.13 (s, 1H); 13C NMR
(100 MHz, CDCl3) d 52.23 (CH3), 52.89 (CH3), 53.01
(CH3), 53.13 (CH3), 124.79 (CH), 125.32 (CH), 126.09
(CH), 126.50 (CH), 126.84 (CH), 128.17 (CH), 128.92
(CH), 129.74, 130.08, 131.30, 133.28, 134.39, 135.05,
135.14 (CH), 137.87, 140.89, 164.77, 165.57, 166.70,
167.39; HR-APCI-MS calcd for C24H20O8 ([MCH]C)
437.1236, found 437.1227.
internally to tetramethylsilane as a standard. 13C NMR
spectra in CDCl3 were referenced to the solvent resonance,
and methyl, methylene, and methyne signals were assigned
by DEPT spectra. 19F NMR spectra in CDCl3 were
referenced externally to trifluoroacetic acid at K76.5 ppm.
Mass spectra were obtained on JEOL JMS-T100LC
(AccuTOF; APCI/ESI-TOF MS). Gel permeation column
chromatography was performed on a Japan Analytical
Industry LC-908 (eluent: chloroform) with JAIGEL 1H and
2H columns.
4.3.4. Disulfonyl benzene 4d. Phenyl CPA 1a (921 mg,
3.93 mmol) and phenyl(trifluoromethanesulfonyl)acetylene
(1869 mg, 7.98 mmol) were dissolved in 5.5 mL of toluene
and heated at 100 8C for 4 h. The solvent was removed in
vacuo to give crude materials. Purification by silica gel
column chromatography (eluent: 4% ethyl acetate/hexane)
afforded the title compound 4d as a white solid in 31% yield
(695 mg, 1.22 mmol). IR (powder) 3062, 2962, 2921, 2852,
1445, 1426, 1389, 1374, 1260, 1212, 1138, 1109, 1050,
4.2. Materials
Commercially available alkynes were purchased and
purified by distillation or recrystallization before reactions.
Phenyl(trifluoromethanesulfonyl)acetylene was synthesized
as reported.13 All solvents were purified by distillation and
˚
dried on molecular sieves 4 A. All new compounds were
1
1025, 857, 803, 782, 758, 729, 700, 677, 634, 625, 614 cmK1
;
determined to be O98% pure by H NMR spectroscopy.
1H NMR (400 MHz, CDCl3) d 6.97 (m, 2H), 7.06 (m, 2H),
7.21 (m, 6H), 7.4 (m, 4H), 7.5 (m, 1H), 8.56 (s, 1H); 13C
NMR (100 MHz, CDCl3) d 119.47 (q, JZ326 Hz, CF3),
119.53 (q, JZ326 Hz, CF3), 126.67 (CH), 127.13 (CH),
128.11 (CH), 128.13 (CH), 128.48 (CH), 129.29 (CH),
129.54 (CH), 129.86 (CH), 130.75 (CH), 130.90, 134.07,
134.09, 135.27, 137.40, 139.86 (CH), 146.81, 148.04,
152.86; 19F NMR (470 MHz, CDCl3) dK75.26 (s),
K72.14 (s); HR-ESI-MS calcd for C26H16F6O4S2Na
([MCNa]C) 593.0292, found 593.0296.
4.3. Synthetic procedure and physical properties
4.3.1. Biphenyl-2,3,4,5-tetracarboxylic acid tetramethyl
ester 4a3 Phenyl CPA 1a (649 mg, 3.50 mmol) and DMAD
(1.48 mL, 12.0 mmol) were dissolved in 0.75 mL of toluene
and heated at 100 8C for 1 h. The solvent was removed in
vacuo to give crude materials. Purification by silica gel
column chromatography (eluent: 20% ethyl acetate/hexane)
afforded the title compound 4a as a white solid in 59% yield
(684 mg, 1.77 mmol). IR and NMR spectra matched with
those reported in the literature.
4.3.5. [1,10;20,100]Terphenyl-40,50-dicarboxylic acid
dimethyl ester 5.14 CPDA 2a (17.9 mg, 50.0 mmol) and
phenylacetylene (36.6 mL, 0.300 mmol) were dissolved in
0.60 mL of toluene and heated at 100 8C for 110 h.
Purification by silica gel column chromatography (eluent:
20% ethyl acetate/hexane) afforded the title compound 5 as
a white solid in 97% yield (100 mg, 0.290 mmol). IR
(powder) 3058, 3025, 3014, 2956, 1721, 1611, 1602, 1495,
1437, 1391, 1324, 1275, 1245, 1227, 1194, 1138, 1079,
1054, 1030, 963, 915, 886, 824, 782, 772, 754, 739,
699 cmK1; 1H NMR (400 MHz, CDCl3) d 3.93 (s, 6H), 7.13
(m, 4H), 7.23 (m, 6H), 7.80 (s, 2H); 13C NMR (100 MHz,
CDCl3) d 52.62 (CH3), 127.33 (CH), 128.07 (CH), 129.52
(CH), 130.66, 131.16 (CH), 139.45, 143.32, 167.73. Anal.
Calcd for C22H18O4: C, 76.29; H, 5.24. Found: C, 76.05; H,
5.23.
4.3.2. 40-Methoxybiphenyl-2,3,4,5-tetracarboxylic acid
tetramethyl ester 4b. Anisyl CPA 1b (61.6 mg,
0.250 mmol) and DMAD (123 mL, 1.00 mmol) were
dissolved in 0.25 mL of toluene and heated at 100 8C for
1 h. The solvent was removed in vacuo to give crude
materials. Purification by silica gel column chromatography
(eluent: 40% ethyl acetate/hexane) afforded the title
compound 4b as a white solid in 63% yield (66.0 mg,
0.159 mmol). IR (powder) 2952, 2840, 1731, 1721, 1607,
1594, 1559, 1515, 1443, 1432, 1391, 1341, 1277, 1246,
1227, 1179, 1160, 1113, 1102, 1025, 1005, 994, 957, 917,
874, 847, 828, 805, 797, 785, 758, 749, 727, 668 cmK1; 1H
NMR (400 MHz, CDCl3) d 3.66 (s, 3H), 3.85 (s, 3H), 3.88
(s, 3H), 3.92 (s, 3H), 3.95 (s, 3H), 6.95 (d, JZ8.4 Hz, 2H),
7.27 (d, JZ8.4 Hz, 2H), 8.08 (s, 1H); 13C NMR (100 MHz,
CDCl3) d 52.61 (CH3), 52.95 (CH3), 52.98 (CH3), 53.18
(CH3), 55.28 (CH3), 114.04 (CH), 129.46 (CH), 129.98,
130.16, 130.33, 133.49, 134.08 (CH), 136.52, 141.78,
159.88, 164.98, 165.70, 167.50, 167.64. Anal. Calcd for
C21H20O9: C, 60.58; H, 4.84. Found: C, 60.48; H, 4.90.
4.3.6. 6-Pyrimidin-5-yl-biphenyl-3,4-dicarboxylic acid
dimethyl ester 6. CPDA 2a (89.6 mg, 0.250 mmol) and
5-ethynylpyrimidine (26.0 mg, 0.250 mmol) were dissolved
in 0.50 mL of chlorobenzene and refluxed for 24 h. The
solvent was removed in vacuo to give crude materials.
Purification by silica gel column chromatography (eluent:
40% ethyl acetate/hexane) afforded the title compound 6
as a white solid in 88% yield (77.0 mg, 0.221 mmol). IR
(powder) 2955, 1726, 1607, 1579, 1557, 1543, 1445, 1438,
1428, 1416, 1382, 1354, 1319, 1283, 1270, 1250, 1188,
1133, 1075, 1054, 1033, 960, 933, 911, 888, 828, 793, 780,
4.3.3. 5-Naphthalen-1-yl-benzene-1,2,3,4-tetracarboxylic
acid tetramethyl ester 4c. 1-Naphthyl CPA 1c (200 mg,
0.750 mmol) and DMAD (184 mL, 1.50 mmol) were
dissolved in 0.38 mL of toluene and heated at 100 8C for
31 h. The solvent was removed in vacuo to give crude
materials. Purification by silica gel column chromatography
(eluent: 50% ethyl acetate/hexane) afforded the title
1
769, 741, 730, 706 cmK1; H NMR (400 MHz, CDCl3) d
3.96 (s, 3H!2), 7.12 (m, 2H), 7.30 (m, 3H), 7.82 (s, 1H),

S. Sato et al. / Tetrahedron 61 (2005) 11449–11455
11453
7.84 (s, 1H), 8.52 (s, 2H), 9.10 (s, 1H); 13C NMR (100 MHz,
CDCl3) d 52.90 (CH3!2), 128.31 (CH), 128.80 (CH),
129.62 (CH), 130.91 (CH), 131.13, 131.45 (CH), 132.73,
133.45, 135.76, 138.04, 144.20, 156.75 (CH), 157.40 (CH),
167.03, 167.42. Anal. Calcd for C20H16N2O4: C, 68.96; H,
4.63; N, 8.04. Found: C, 69.23; H, 4.75; N, 7.92.
(CH), 127.24 (CH), 128.04 (CH), 128.35 (CH), 129.01
(CH), 129.57 (CH), 130.37 (CH), 130.56, 132.13, 136.02,
139.06, 142.80, 158.29, 166.31, 168.80. The coupling
constant of two protons on benzene ring measured JZ
1.8 Hz, which indicate their meta-relationship.
4.3.9. 6-(4,4,5,5-Tetramethyl[1,3,2]dioxaborolan-2-yl)-
biphenyl-3,4-dicarboxylic acid dimethyl ester 10.
CPDA 2a (358 mg, 1.00 mmol), ethynylboronate ester
(304 mg, 2.00 mmol), and dodecane (113 mL, 0.500 mmol,
internal standard) were dissolved in 0.50 mL of chloro-
benzene and heated at 120 8C. Complete consumption of
alkyne was confirmed after 42 h by GC analysis. The
solvent was removed in vacuo to give crude materials.
Purification by silica gel column chromatography (eluent:
3% ethyl acetate/toluene) afforded the title compound 10 as
a viscous liquid in 68% yield (269 mg, 0.679 mmol). IR
(liquid) 2979, 2952, 2111, 2092, 1727, 1546, 1509, 1486,
1436, 1389, 1324, 1285, 1247, 1131, 1096, 1067, 1028, 963,
4.3.7. 6-Cyclohex-1-enyl-biphenyl-3,4-dicarboxylic acid
dimethyl ester 7. CPDA 2a (179 mg, 0.500 mmol) and
1-ethynylcyclohexene (2.06 mL, 17.5 mmol) were dis-
solved in 0.95 mL of t-butanol and heated at 150 8C for
21 h in a sealed tube. The solvent was removed in vacuo to
give crude materials. Purification by silica gel column
chromatography (eluent: 15% ethyl acetate/hexane)
afforded the title compound 7 as a white solid in 75%
yield (131 mg, 0.375 mmol). IR (KBr) 3445, 2931, 1730,
1436, 1308, 1246, 1130, 1075, 968, 910, 772, 701 cmK1; 1H
NMR (500 MHz, CDCl3) d 1.43–1.48 (m, 2H), 1.49–1.54
(m, 2H), 1.75–1.79 (m, 2H), 2.07–2.12 (m, 2H), 3.90 (s,
3H), 3.93 (s, 3H), 5.75 (m, 1H), 7.32–7.43 (m, 5H), 7.59 (s,
1H), 7.67 (s, 1H); 13C NMR (75 MHz, CDCl3) d 21.70
(CH2), 22.67 (CH2), 25.59 (CH2), 28.76 (CH2), 52.56
(CH2), 52.60 (CH2), 127.56 (CH), 128.12 (CH), 128.62
(CH), 129.29 (CH), 129.83, 129.97 (CH), 130.57, 130.70
(CH), 138.05, 140.21, 142.43, 146.49, 167.85, 168.14. Anal.
Calcd for C22H22O4: C, 75.41; H, 6.33. Found: C, 75.28; H,
6.37.
1
895, 853, 828, 768, 739, 702, 689, 668 cmK1; H NMR
(500 MHz, CDCl3) d 1.21 (s, 12H), 3.91 (s, 3H), 3.92 (s,
3H), 7.38 (m, 5H), 7.68 (s, 1H), 8.08 (s, 1H); 13C NMR
(100 MHz, CDCl3) d 24.56 (CH3), 52.59 (CH3), 52.70
(CH3), 84.29, 127.81 (CH), 128.00 (CH), 128.87, 128.93
(CH), 129.05 (CH), 132.69 (br, CB), 133.54, 135.16 (CH),
141.18, 150.58, 167.85, 168.21. Anal. Calcd for
C22H25O6B: C, 66.69; H, 6.36. Found: C, 66.44; H, 6.50.
3
We observed JCH HMBC correlations between methyne
protons and carbonyl carbons and determined the positions
of substituents as shown in Table 2.
4.3.8. 6-Phenoxymethyl-biphenyl-3,4-dicarboxylic acid
dimethyl ester 8. CPDA 2a (17.9 mg, 50.0 mmol) and
phenylprop-2-yl ether (15.4 mL, 120 mmol) were dissolved
in 0.30 mL of 1,2,4-trichlorobenzene and stirred at 150 8C
for 8 days. Purification by silica gel column chromato-
graphy (eluent: 20% ethyl acetate/hexane) afforded the 5:1
mixture of regioisomers 8 and 9 in 91% yield (17.2 mg,
45.7 mmol). Anal. Calcd for C23H20O5: C, 73.39; H, 5.36.
Found: C, 73.28; H, 5.51. Purification by gel permeation
column chromatography afforded the title compound 8 as a
viscous liquid in 76% yield (14.3 mg, 38.0 mmol) and minor
product 9 as a viscous liquid in 15% yield (2.8 mg,
7.4 mmol).
4.3.10. 3,4,5-Triphenylphthalic acid dimethyl ester 11.15
CPDA 2a (17.9 mg, 50.0 mmol) and diphenylacetylene
(17.8 mg, 100 mmol) were dissolved in 0.10 mL of diphenyl
ether and refluxed for 12 h. Purification by silica gel column
chromatography (eluent: 5% ethyl acetate/toluene) afforded
the title compound 11 as a white solid in 39% yield (8.2 mg,
19 mmol). IR (powder) 3053, 3026, 2948, 1733, 1723, 1588,
1555, 1497, 1445, 1426, 1337, 1297, 1262, 1235, 1202,
1146, 1073, 1063, 1030, 965, 911, 849, 807, 766, 753,
700 cmK1; 1H NMR (400 MHz, CDCl3) d 3.56 (s, 3H), 3.92
(s, 3H), 6.76 (m, 2H), 6.93 (m, 3H), 7.06 (m, 4H), 7.12 (m,
3H), 7.16 (m, 3H), 8.11 (s, 1H); 13C NMR (100 MHz,
CDCl3) d 52.15 (CH3), 52.58 (CH3), 126.13, 126.40 (CH),
126.89 (CH), 127.01 (CH), 127.15 (CH), 127.23 (CH),
127.76 (CH), 129.64 (CH), 130.19 (CH), 130.82 (CH),
131.02 (CH), 135.15, 137.59, 138.07, 140.29, 140.31,
142.76, 144.78, 165.88, 169.10. Anal. Calcd for
C22H18O4: C, 79.60; H, 5.25. Found: C, 79.50; H, 5.47.
Compound 8. IR (KBr) 3059, 3029, 2951, 1730, 1599, 1587,
1496, 1435, 1393, 1313, 1242, 1193, 1170, 1133, 1072,
1
1031, 966, 912, 848, 793, 756, 704, 692 cmK1; H NMR
(400 MHz, CDCl3) d 3.91 (s, 3H), 3.93 (s, 3H), 4.96 (s, 2H),
6.85 (m, 2H), 6.94 (m, 1H), 7.25 (m, 2H), 7.34–7.45 (m,
5H), 7.68 (s, 1H), 8.06 (s, 1H); 13C NMR (100 MHz,
CDCl3) d 52.68 (CH3!2), 67.06 (CH2), 114.78 (CH),
121.27 (CH), 128.23 (CH), 128.56 (CH), 128.76 (CH),
129.46 (CH), 129.48 (CH), 130.51, 130.78, 131.40 (CH),
137.68, 138.42, 144.28, 158.15, 167.67, 167.78. We
4.3.11. Diels–Alder adduct of CPDA and 2,5-norborna-
diene 12.6 CPDA 2a (143 mg, 0.400 mmol) was dissolved
in 0.80 mL of 2,5-norbornadiene and stirred at 80 8C for 7 h,
and the solvent was removed in vacuo to give the title
compound 12 as a white solid in 98% yield (176 mg,
0.392 mmol). A single crystal was obtained by recrystalliza-
tion from methylene chloride/pentane, and the structure was
determined by X-ray diffraction study. IR (powder) 2962,
2946, 1740, 1717, 1600, 1465, 1447, 1434, 1362, 1312,
1299, 1275, 1264, 1250, 1233, 1221, 1210, 1191, 1177,
1158, 1127, 1113, 1094, 1073, 1059, 1032, 1003, 974, 965,
942, 924, 909, 895, 868, 853, 814, 801, 785, 770, 747, 720,
3
observed JCH HMBC correlations between methyne
protons and carbonyl carbons and determined the positions
of substituents as shown in Table 2.
Compound 9. IR (KBr) 2951, 2919, 2858, 1730, 1599, 1496,
1456, 1434, 1382, 1331, 1242, 1159, 1107, 1068, 1033, 986,
755, 693 cmK1; 1H NMR (400 MHz, CDCl3) d 3.92 (s, 3H),
3.94 (s, 3H), 5.19 (s, 2H), 6.97 (m, 3H), 7.29 (m, 2H), 7.41
(m, 1H), 7.47 (m, 2H), 7.60 (s, 2H), 7.97 (m, 1H), 8.14
(d, JZ1.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 52.69
(CH3), 52.77 (CH3), 67.13 (CH2), 114.84 (CH), 121.39
1
702, 687, 656, 621 cmK1; H NMR (500 MHz, CDCl3) d

11454
S. Sato et al. / Tetrahedron 61 (2005) 11449–11455
˚
˚
0.43 (s, 3H), 0.70 (s, 3H), 0.99 (d, JZ10 Hz, 1H), 1.84 (d,
JZ10 Hz, 1H), 2.61 (d, JZ2 Hz, 1H), 2.82 (d, JZ2 Hz,
1H), 3.00 (d, JZ11 Hz, 1H), 3.04 (d, JZ7 Hz, 1H), 3.16 (d,
JZ11 Hz, 1H), 3.17 (d, JZ7 Hz, 1H), 3.23 (d, JZ11 Hz,
1H), 3.37 (d, JZ11 Hz, 1H), 3.78 (s, 3H), 3.79 (s, 3H), 6.30
(dd, JZ3, 3 Hz, 1H), 6.38 (dd, JZ3, 3 Hz, 1H), 7.06 (s,
1H), 7.35 (m, 3H), 7.54 (m, 2H); 13C NMR (125 MHz,
CDCl3) d 22.83 (CH3), 23.09 (CH3), 30.54, 41.44 (CH),
42.08 (CH2), 42.44 (CH), 46.59 (CH), 47.25 (CH), 51.89
(CH3), 51.96 (CH3), 64.64, 65.11, 72.27 (CH2),72.36 (CH2),
121.05, 127.43 (CH), 128.12 (CH), 128.76 (CH), 135.62,
136.99, 140.19 (CH), 141.49 (CH), 147.80 (CH), 164.13,
171.55. Anal. Calcd for C27H30O6: C, 71.98; H, 6.71.
Found: C, 71.80; H, 6.75.
bZ7.8120(4) A, cZ23.596(2) A, bZ101.878(5)8, VZ
1897.3(4) A , ZZ4, DcalcdZ1.353 g cmK3, RZ0.071,
3
˚
RwZ0.144.
4.4.2. Selected X-ray crystallographic data for com-
˚
pound 4d. C26H16F6O4S2, triclinic, P-1, aZ10.2070(9) A,
˚
˚
bZ11.1210(6) A, cZ12.0070(9) A, aZ84.070(4)8, bZ
3
˚
80.885(4)8, gZ66.172(4)8, VZ1229.9(2) A , ZZ2,
DcalcdZ1.541 g cmK3, RZ0.045, RwZ0.094.
4.4.3. Selected X-ray crystallographic data for com-
˚
6
pound 12. C27H30O6, triclinic, P-1, aZ9.9730(5) A, bZ
˚
˚
11.3770(10) A, cZ10.8700(10) A, aZ94.578(4)8, bZ
3
˚
99.652(5)8, gZ104.643(5)8, VZ1166.7(2) A , ZZ2,
DcalcdZ1.282 g cmK3, RZ0.167, RwZ0.486.
4.3.12. Dimethyl 4-phenylphtalate 13.6 Diels–Alder
adduct 12 (113 mg, 0.250 mmol) was dissolved in 2.0 mL
of tetralin in a sealed tube. The reaction vessel was heated at
230 8C for 5 days. Purification by silica gel column
chromatography (eluent: 5% ethyl acetate/toluene) afforded
the title compound 13 as a white solid in 86% yield
(58.4 mg, 0.216 mmol) and tetraalkoxyethylene 1416
(eluent: 40% ethyl acetate/hexane) as a white solid in 52%
yield (14.6 mg, 0.0644 mmol).
Acknowledgements
This study was financially supported by Monbukagakusho,
Japan (the 21st Century COE Program for Frontiers in
Fundamental Chemistry to E. N. and grant-in-aid for
Scientific Research, Young Scientists (A) to H. I.) and
SUNBOR (to H. I.).
Compound 13. IR (powder) 3014, 2956, 1725, 1605, 1582,
1566, 1508, 1436, 1395, 1298, 1285, 1272, 1248, 1194,
1160, 1129, 1077, 1046, 1025, 1000, 959, 922, 897, 863,
824, 793, 780, 766, 746, 699, 675 cmK1 1H NMR
;
References and notes
(500 MHz, CDCl3) d 3.93 (s, 3H), 3.94 (s, 3H), 7.46 (m,
3H), 7.62 (m, 2H), 7.74 (dd, JZ2, 8 Hz, 1H), 7.84 (d, JZ
8 Hz, 1H), 7.91 (d, JZ2 Hz, 1H); 13C NMR (100 MHz,
CDCl3) d 52.56 (CH3), 52.66 (CH3), 127.12 (CH), 127.25
(CH), 128.38 (CH), 128.94 (CH), 129.21 (CH), 129.63
(CH), 129.78, 132.99, 138.86, 144.24, 167.55, 168.25. Anal.
Calcd for C23H25NO6: C, 71.10; H, 5.22. Found: C, 70.96;
H, 5.16.
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1
1115, 1094, 1073, 1061, 1034, 762, 699 cmK1; H NMR
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4.4. X-ray crystallographic study
Suitable crystals of 4a, 4d, and 12 were obtained by
recrystallization from methylene chloride/pentane. X-ray
diffraction study was carried out on a MacScience DIP2030
Imaging Plate diffractometer. Space group determination,
structural solution, and refinement were performed using a
maXus program. Crystallographic data (excluding structure
factors) have been deposited with the Cambridge Crystallo-
graphic Data Centre as supplementary publication number
CCDC 273014 (4a), 273015 (4d), and 244460 (12). Copies
of the data can be obtained, free of charge, on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax:
C44 1223 336033 or e-mail: deposit@ccdc.cam.ac.uk).
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¨
12. Watson, M. D.; Fechtenkotter, A.; Mullen, K. Chem. Rev.
¨
4.4.1. Selected X-ray crystallographic data for com-
˚
pound 4a. C20H18O8, monoclinic, P21/c, aZ10.518(2) A,
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¨
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