Ortho-disubstitution reactions of aromatic rings with homo-conjugated bicyclo[2.2.2]octa-2,5-diene derivatives in the presence of palladium(II) acetate

Article abstract of DOI:10.1016/S0040-4020(02)01126-2

Bicyclo[2.2.2]octa-2,5-diene derivatives 5 and 7 reacted with aromatic compounds such as benzene, naphthalene, anthracene, phenanthrene, and tropone in the presence of Pd(OAc)₂ to afford ortho-disubstituted aromatics 6 and 8-12. Since the yields and regioselectivity were generally low, the reaction conditions were optimized by using iodoarenes as reagents to provide sufficient yields and regioselectivity. In order to investigate reactivities of diene moieties, several kinds of homo-conjugated dienes were surveyed for the reaction. Only dienes containing a bicyclo[2.2.2]octa-2,5-diene skeleton gave the ortho-disubstituted aromatics.

Full text of DOI:10.1016/S0040-4020(02)01126-2

Tetrahedron 58 (2002) 9081–9088
ortho-Disubstitution reactions of aromatic rings with
homo-conjugated bicyclo[2.2.2]octa-2,5-diene derivatives in the
presence of palladium(II) acetate
a,*
a
Katsuhiro Saito, Katsuhiko Ono, Toshifumi Takeda, Shingo Kiso, Kazuya Uenishi
a
a
a
b
and Masatoshi Kozaki
a
Department of Applied Chemistry, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555, Japan
Graduate School of Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan
b
Received 23 April 2002; accepted 4 September 2002
Abstract—Bicyclo[2.2.2]octa-2,5-diene derivatives 5 and 7 reacted with aromatic compounds such as benzene, naphthalene, anthracene,
phenanthrene, and tropone in the presence of Pd(OAc) to afford ortho-disubstituted aromatics 6 and 8–12. Since the yields and
2
regioselectivity were generally low, the reaction conditions were optimized by using iodoarenes as reagents to provide sufficient yields and
regioselectivity. In order to investigate reactivities of diene moieties, several kinds of homo-conjugated dienes were surveyed for the
reaction. Only dienes containing a bicyclo[2.2.2]octa-2,5-diene skeleton gave the ortho-disubstituted aromatics. q 2002 Elsevier Science
Ltd. All rights reserved.
1
. Introduction
octa-2,5-diene derivatives 5 were employed, a new type of
tetracyclic compounds with benzene was obtained. The
reactions probably proceeded via homo-p-allyl palladium
complexes. We report herein the ortho-disubstitution
reactions of aromatic compounds with the homo-conjugated
Homo-conjugated dienes such as norbornadiene (1),
bicyclo[2.2.2]octa-2,5-diene (2), bicyclo[3.2.2]nona-6,8-
diene (3), and barrelene (4) are highly attractive compounds
to investigate through-space interactions and reactivity
because their double bonds are fixed close each other.
Most studies have been carried out on their photochemical
dienes using Pd(OAc) and properties of the diene moieties.
2
1
2
reactions, Diels–Alder reactions with dienophiles, and
3
organometalation. On the other hand, p-allyl palladium
complexes are very useful for organic synthesis and much
4
research effort has been conducted. For example, butadiene
reacts with Pd salts to afford stable p-allyl palladium
complexes, which produce 1,4-disubstituted 2-butene
derivatives after reactions with nucleophiles. In this context,
reactions of homo-conjugated dienes with Pd salts are of
much interest since those provide the possibility of forming
homo-p-allyl palladium complexes. At present, several
works have been reported on norbornadiene, discussed that
homo-p-allyl palladium complexes were considered as a
transition state species or a metastable intermediate in the
2
. Results and discussion
2
.1. Reactions of homo-dienes with aromatic compounds
2
,4
6
Tricyclo[3.2.2.0 ]nona-6,9-diene derivatives 5a–d were
heated at 60–808C for 20–48 h in dry benzene with
Pd(OAc)2 (1 mol equiv.) and NaOAc (5 mol equiv.) to
afford compounds 6a–d (Table 1). Molecular structures of
5
6a–d were determined as follows. In mass spectra
molecular ion peaks indicated 1:1 compositions of 5 and
reaction path. However, there is no report on reactions of
other homo-conjugated dienes with Pd salts. Therefore, we
investigated reactions of several kinds of homo-conjugated
dienes with Pd(OAc) in dry benzene. When bicyclo[2.2.2]-
1
13
benzene. H and C NMR analyses supported ortho-
disubstituted benzene moieties. Additionally, disappearance
of signals for the olefin parts suggested reactions of benzene
to the homo-conjugated double bonds. The molecular
structure was ultimately determined by an X-ray structural
analysis of 6c (Fig. 1) as indicated in a preliminary report
2
7
Keywords: metalation; palladium and compounds; dienes; aryl halides.
*
Corresponding author. Tel.: þ81-52-735-5224; fax: þ81-52-735-5247;
e-mail: saito@ach.nitech.ac.jp
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)01126-2

9082
K. Saito et al. / Tetrahedron 58 (2002) 9081–9088
Table 1. Reactions of dienes 5 with benzene
Diene
R
1
R
2
Temperature (8C)
Time (h)
Yield (%)
5
5
5
5
a
b
c
H
H
CN
CO
H
CN
H
60
80
80
60
24
48
20
20
6a 31
6b 57
6c 43
6d 20
d
2
Et
H
2
Reaction conditions: 5 (3 mmol), Pd(OAc) (3 mmol), NaOAc (15 mmol), benzene (30 ml).
ethyl acetate were refluxed in the presence of Pd(OAc) and
2
NaOAc for 4 days to give three isomers of ortho-
disubstituted aromatics 9a–c (entry 1). Molecular structures
1
of 9b and 9c were undoubtedly characterized by H NMR
spectra. Because it was considered that H(f) proton of 9b
was deshielded by ring electrons on the naphthalene moiety,
the H(f) proton was used for distinguishing 9b (d ¼3.73
Hf
ppm) from the other isomers 9c (d ¼3.30 ppm) and 9a
Hf
(
d ¼3.28 ppm). The major product was 9a, suggesting that
Hf
the reaction proceeded to minimize steric hindrance.
Anthracene and phenanthrene also reacted under the same
conditions to afford mixtures of stereo isomers 10 and 11,
respectively (entries 2 and 3). Tropone was also applied for
the reaction as an example of non-benzenoid aromatics.
Stereo isomer of product 12 could not be characterized
because only a single isomer was obtained in a low yield
(entry 4).
2.2. Reactions of homo-dienes with iodoarenes
Figure 1. Molecular structure of compound 6c (ORTEP).
Although several types of aromatic compounds reacted with
homo-conjugated diene 5d as described above, the yields
and regioselectivity were generally not high. Therefore,
iodoarenes were used for the reaction since insertion of
Pd(II) to C–H bonds of aromatics were considered as a
crucial step according to many research reports on
8
(CCDC reference number 186676). The yields were
slightly dependent on functional groups (R , R ) as shown
1
2
in Table 1. The three-membered ring, however, seemed not
to be important in the reactions since diene 7 also reacted
with benzene to give compound 8 in 27% yield (Scheme 1).
In these reactions no starting material was recovered and
other products such as mono-substituted compounds were
9
organometalation. Iodobenzene was allowed to react with
diene 5d in refluxing acetonitrile containing Pd(OAc) and
2
NaOAc to give compound 6d in 52% yield. Furthermore,
addition of n-Bu NCl (1 mol equiv.) increased the yield up
4
5
e,f
not obtained at all.
to 73%. It has been known that use of n-Bu NCl is effective
4
1
0
for many Pd-catalyzed reactions. Table 3 summarizes
yields of products 6a–e obtained by the reactions of dienes
5a–e using iodobenzene. The yields are higher than those
listed in Table 1 and reaction times are shorter except for 6b
In order to expand applicability to other aromatic com-
pounds, reactions of diene 5d with condensed aromatic rings
were performed (Table 2). Diene 5d and naphthalene in
Scheme 1. Reaction of diene 7 with benzene.

K. Saito et al. / Tetrahedron 58 (2002) 9081–9088
Table 2. Reactions of diene 5d with several types of aromatic compounds
9083
Entry
ArH
Product
Yield (%)
a
1
9a 16;
9
9
b 7;
c 3
a
2
10a 13;
1
1
0b 4;
0c 3
a
3
11 8
b
4
12 4
Reaction conditions: 5d (R
AcOEt (10 ml).
MeCN (8 ml).
1
¼CO
2
Et, R
3
¼CO
2 2
Me, 1 mmol), ArH (3–9 mmol), Pd(OAc) (1 mmol), NaOAc (5 mmol), reflux, 4 days.
a
b
and 6e. Thus, the rate-determining step governed by
organometalation was accelerated. The yield, however,
decreased to only 15% when bromobenzene was employed
for a reaction with 5d.
shown in Table 4. Although a stereo isomer of 13 was not
confirmed, entry 1 indicates introduction of functional
groups into aromatic rings of products. Entries 2 and 3 show
the improved yields and regioselectivity, which demon-
strates usefulness of ortho-disubstitution reactions for
synthesizing unique pentacycles.
Other types of iodoarenes were applied for the reactions as
Table 3. Reactions of dienes 5 with iodobenzene
Diene
R
1
R
2
Time (h)
Yield (%)
5
5
5
5
5
a
b
c
d
e
H
H
CN
CO
CO
H
CN
H
H
Me
6
48
6
6
6
6a 68
6b 58
6c 79
6d 73
6e 35
2
Et
Me
2
Reaction conditions: 5 (1 mmol), PhI (3 mmol), Pd(OAc)
2
(1 mmol), NaOAc (5 mmol), n-Bu
4
NCl (1 mmol), MeCN (6 ml), reflux.

9084
K. Saito et al. / Tetrahedron 58 (2002) 9081–9088
Table 4. Reactions of diene 5d with iodoarenes
Entry
ArI
Product
Yield (%)
1
13 30
2
9b 54
3
12 22
Reaction conditions: 5d (R
3
1
¼CO
2
Et, R
3
¼CO
2
Me, 1 mmol), ArI (3 mmol), Pd(OAc)
2
(1 mmol), NaOAc (5 mmol), n-Bu
4
NCl (1 mmol), MeCN (6 ml), reflux,
days.
Table 5. Reactions of homo-conjugated dienes with iodobenzene
Entry
1
Diene
Time
Product
Yield (%)
11
3 days
2
3 days
30
60
3
4
6 h
20 h
Decomp
Decomp
5
3 days
Reaction conditions: diene (R
3
¼CO
2 2 4
Me, 1 mmol), PhI (3 mmol), Pd(OAc) (1 mmol), NaOAc (5 mmol), n-Bu NCl (1 mmol), MeCN (6 ml), reflux.

K. Saito et al. / Tetrahedron 58 (2002) 9081–9088
9085
Scheme 2. Mechanism of ortho-disubstitution reaction.
2.3. Scope and limitations of ortho-disubstitution
reactions and mechanisms
derivatives with aromatic compounds in the presence of
Pd(OAc) . Many kinds of aromatic rings were applied to
2
show the scope and limitations of the reaction. After
optimizing reaction conditions, the products were obtained
in reasonable yields as iodoarenes were employed. These
reactions proceeded in only dienes containing a
bicyclo[2.2.2]octa-2,5-diene skeleton, which strongly
reflected the specific properties of the diene moieties.
The ortho-disubstitution reactions were studied using a
series of homo-conjugated diene moieties to show the scope
and limitations of the reaction (Table 5). Norbornadiene 14
reacted with iodobenzene to afford compound 18 (entry1),
1
1
and this result was supported by other reports. Diene 15
afforded benzene derivative 19 as a result of elimination of
cyclobutadiene like a retro-Diels–Alder reaction (entry
1
2
2
). Diene 7 produced compound 8 in 60% yield as
3. Experimental
3.1. General
described above (entry 3). No significant compound was
obtained from both reactions using dienes 16 and 17,
respectively (entries 4 and 5). These results demonstrated
that only bicyclo[2.2.2]octa-2,5-diene derivatives yielded
the products and the ortho-disubstitution reactions strongly
depended on properties of the homo-conjugated dienes.
All solvents were dried and purified by usual methods.
Column chromatography was performed using Wakogel
C200. Melting points were measured on a Yanagimoto hot-
stage apparatus and are uncorrected. IR spectra were
obtained with a JASCO FT/IR-5300 spectrometer. Mass
spectra (EI) were taken with a Hitachi 220A spectrometer
operating at 70 eV by a direct inlet system. Elemental
analyses were performed on YANACO MT-3 CHN
The reaction mechanisms were speculated as Scheme 2
from research reports concerning organometalation of
Pd(OAc) to C–X bonds (X¼I, Br, Cl) using inorganic
2
5e,10
5,13
salts and addition to the double bonds.
was a reaction of Pd(OAc) with iodoarene (e.g. iodo-
The first step
1
13
2
CORDER. H and C NMR spectra were recorded with
Varian GEMINI (200 and 300 MHz) spectrometers with
benzene) in the presence of NaOAc yielding a Ph-Pd–X
X¼I or OAc) complex. This complex followed by addition
1
(
to homo-conjugated diene (e.g. 5) to form complex A.
tetramethylsilane as an internal standard. In the H NMR
spectra, protons assigned to pentacyclo-skeletons are
described using H –H symbols as shown in Fig. 2.
5
f
Then complex A was transformed to complex C and/or D,
which afforded 6 with release of a Pd(0) complex. In this
connection complex B was also consistently thinkable as an
intermediate to give complex D. From the mechanistic
points of view, the different reactivities of homo-conjugated
dienes are not clear yet, and further investigation is under
study.
a
h
In conclusion, we offered a unique type of ortho-
disubstitution reactions via homo-p-allyl palladium com-
plexes as transition state species or intermediates, which
were produced by reactions of bicyclo[2.2.2]octa-2,5-diene
1
Figure 2. Symbols in HNMR analyses.

9086
K. Saito et al. / Tetrahedron 58 (2002) 9081–9088
þ
3
.1.1. Reactions of dienes (5a–d, 7) with benzene. A
mixture of 5a (0.70 g, 3.0 mmol), Pd(OAc)2 (0.67 g,
.0 mmol), and NaOAc (1.23 g, 15.0 mmol) in dry benzene
30 ml) was stirred at 608C for 24 h under nitrogen. An
172.7; MS m/z (rel. intensity) 382 (M , 11), 351 (27), 318
(22), 277 (49), 244 (100). Found: m/z 382.1405. Mass calcd
for C H O : 382.1414.
3
(
2
2 22 6
insoluble solid was removed by filtration and the filtrate was
concentrated. To the residue ethyl acetate and water were
added. The organic layer was separated and the aqueous
layer was extracted with ethyl acetate. The combined
organic solution was dried over Na SO and concentrated.
8: Yield 27%; colorless crystals (benzene); mp 140–1418C;
IR (KBr) 2957, 1734, 1720 cm2 ; H NMR (CDCl ) d 1.64
1 1
3
(m, 2H), 2.00 (m, 1H), 2.03 (m, 1H), 2.21 (m, 2H), 2.45 (dt,
1H, J¼7.7, 2.9 Hz), 3.20 (br s, 1H), 3.51 (s, 3H, CH ), 3.88
3
(s, 3H, CH ), 7.08 (m, 2H, Ar), 7.18 (d, 1H, J¼6.9 Hz, Ar),
2
4
3
1
3
The obtained solid was recrystallized from benzene–n-
hexane to give 6a (0.29 g, 31%) as colorless crystals: mp
7.53 (d, 1H, J¼7.5 Hz, Ar); C NMR (CDCl ) d 14.3, 18.4,
3
33.8, 38.3, 39.0, 45.5, 51.5, 51.8, 56.3, 59.3, 120.5, 123.9,
125.2, 125.4, 147.4, 149.1, 172.3, 172.9; MS m/z (rel.
1
1
1
59–1608C; IR (KBr) 3005, 2951, 1748, 1738, 1721, 1705,
1
441, 1302, 1277, 1258, 1200, 1136, 1061, 758, 681 cm2
H NMR (CDCl ) d 0.13–0.14 (m, 2H, H ), 0.63 (m, 1H,
;
intensity) 298 (M , 17), 266 (30), 238 (33), 207 (37), 179
þ
(100). Found: C, 72.29; H, 6.01%. Calcd for C H O : C,
72.47; H, 6.08%.
3
a,b
18 18 4
H ), 1.29 (m, 1H, H ), 1.69 (dt, 1H, J¼7.7, 1.6 Hz, H ), 2.52
d
c
g
(
dt, 1H, J¼5.0, 2.0 Hz, H ), 2.60 (m, 1H, H ), 2.85 (dd, 1H,
e
f
J¼7.7, 4.3 Hz, H ), 3.10 (s, 3H, CH ), 3.59 (s, 3H, CH ),
3.1.2. Reaction of diene (5d) with naphthalene. A mixture
of 5d (0.31 g, 1.0 mmol), naphthalene (0.39 g, 3.0 mmol),
Pd(OAc)2 (0.23 g, 1.0 mmol), and NaOAc (0.41 g,
5.0 mmol) was refluxed in dry ethyl acetate (10 ml) for 4
days under nitrogen. An insoluble solid was removed by
filtration. The organic solution was washed with water and
dried over Na SO . After removal of the solvent, the
h 3 3
1
3
6
3
1
.80–7.59 (m, 4H, Ar); C NMR (CDCl ) d 6.9, 7.3, 8.6,
3
7.0, 39.2, 40.5, 44.5, 51.5, 51.8, 57.0, 59.4, 120.5, 124.2,
25.4, 125.5, 147.6, 147.6, 171.7, 172.9; MS m/z (rel.
þ
intensity) 310 (M , 2), 263 (78), 219 (65), 191 (100), 165
(
36). Found: C, 73.59; H, 5.90%. Calcd for C H O : C,
19 18 4
7
3.53; H, 5.85%.
2
4
residue was separated with column chromatography (silica
gel, n-hexane–ethyl acetate¼6:1) to provide 9a (41 mg,
16%), 9b (19 mg, 7%), and 9c (10 mg, 3%). Both 9a and 9b
were recrystallized from ethanol.
Similar reactions were applied for dienes 5b–d and 7 to
give compounds 6b–d and 8.
6
2
1
2
b: Yield 57%; colorless crystals (benzene); mp 205–
2
1 1
068C; IR (KBr) 2236, 1715 cm ; H NMR (CDCl ) d
3
9a: Colorless crystals; mp 233–2348C; IR (KBr) 2953,
1714 cm2 ; H NMR (CDCl ) d 1.29 (t, 3H, J¼7.1 Hz,
1
1
.44 (m, 1H, H ), 1.60 (t, 1H, J¼7.7 Hz, H ), 2.10–2.30 (m,
d
a
3
H, H ), 2.79 (dt, 1H, J¼6.0, 1.9 Hz, H ), 2.94 (ddd, 1H,
CH ), 1.66 (m, 1H, H ), 1.73 (t, 1H, J¼3.0 Hz, H ), 1.86
c,g
e
3
d
b
J¼7.8, 4.3, 1.3 Hz, H ), 3.56 (s, 3H, CH ), 3.89 (s, 3H,
(dd, 1H, J¼7.7, 1.9 Hz, H ), 2.18 (m, 1H, H ), 2.75 (dt, 1H,
h
3
g
c
CH ), 4.08 (br s, 1H, H ), 7.07–7.25 (m, 3H, Ar), 7.59 (d,
3
J¼5.5, 1.9 Hz, H ), 2.82 (ddd, 1H, J¼7.7, 4.7, 0.8 Hz, H ),
3.28 (br s, 1H, H ), 3.51 (s, 3H, CH ), 3.94 (s, 3H, CH ),
f 3 3
f
e
h
1
3
1
3
1
H, J¼7.5 Hz, Ar); C NMR (CDCl ) d 5.0, 16.0, 16.9,
3
2.7, 38.8, 39.1, 42.7, 51.8, 52.1, 54.1, 60.6, 119.7, 121.2,
24.5, 126.0, 126.2, 145.2, 147.5, 170.8, 172.0; MS m/z (rel.
4.16 (q, 2H, J¼7.1 Hz, CH ), 7.45 (m, 2H, Ar), 7.55 (s, 1H,
2
1
3
Ar), 7.74 (m, 1H, Ar), 7.83 (m, 1H, Ar), 7.96 (s, 1H, Ar);
NMR (CDCl ) d 14.2, 19.3, 21.9, 25.8, 36.9, 37.1, 38.9,
C
þ
63). Found: C, 71.55; H, 5.05; N, 4.15%. Calcd for
intensity) 335 (M , 2), 303 (100), 244 (42), 216 (72), 174
(
C H NO : C, 71.63; H, 5.11; N, 4.18%.
3
44.1, 51.6, 52.2, 58.6, 60.7, 60.9, 118.7, 119.0, 123.1, 123.3,
127.3, 128.2, 132.0, 132.2, 143.7, 144.2, 171.0, 171.8,
2
0
17
4
þ
(64), 327 (52), 294 (100). Found: m/z 432.1543. Mass calcd
172.5; MS m/z (rel. intensity) 432 (M , 87), 401 (28), 369
6
1
1
c: Yield 43%; colorless crystals (benzene); mp 143–
2
1 1
448C; IR (KBr) 2236, 1723 cm ; H NMR (CDCl ) d
3
for C H O : 432.1566.
26 24 6
.42 (t, 1H, J¼3.5 Hz, H ), 1.71 (m, 1H, H ), 1.87 (dt, 1H,
b
d
J¼7.0, 1.5 Hz, H ), 2.28 (m, 1H, H ), 2.73 (dt, 1H, J¼5.8,
9b: Colorless crystals; mp 164–1658C; IR (KBr) 2953,
g
c
1721 cm2 ; H NMR (CDCl ) d 1.30 (t, 3H, J¼7.1 Hz,
1
1
1
s, 1H, H ), 3.55 (s, 3H, CH ), 3.91 (s, 3H, CH ), 7.03–7.24
.8 Hz, H ), 2.91 (ddd, 1H, J¼7.0, 4.6, 1.1 Hz, H ), 3.11 (br
e
h
3
CH ), 1.70 (m, 1H, H ), 1.82 (t, 1H, J¼3.2 Hz, H ), 1.95
f 3 3
3
d
b
1
3
(m, 3H, Ar), 7.59 (d, 1H, J¼7.5 Hz, Ar); C NMR (CDCl3)
d 6.0, 19.0, 20.0, 35.2, 38.8, 41.3, 45.0, 52.8, 53.1, 54.7,
(dd, 1H, J¼8.1, 1.9 Hz, H ), 2.22 (m, 1H, H ), 2.86 (dt, 1H,
g
c
J¼5.8, 1.9 Hz, H ), 3.02 (dd, 1H, J¼8.1, 5.8 Hz, H ), 3.49
e h
5
1
9.8, 121.0, 121.8, 125.6, 127.0, 127.0, 147.1, 147.3, 171.5,
þ
(s, 3H, CH ), 3.73 (br s, 1H, H ), 3.93 (s, 3H, CH ), 4.18 (q,
3 f 3
72.0; MS m/z (rel. intensity) 335 (M , 2), 303 (100), 244
2H, J¼7.1 Hz, CH ), 7.43 (m, 2H, Ar), 7.66 (d, 1H,
2
(
4
52), 216 (81), 174 (71). Found: C, 71.38; H, 4.92; N,
.14%. Calcd for C H NO : C, 71.63; H, 5.11; N, 4.18%.
J¼8.2 Hz, Ar), 7.78 (d, 1H, J¼8.2 Hz, Ar), 7.82 (dd, 2H,
1
3
J¼7.4, 6.9 Hz, Ar); C NMR (CDCl ) d 14.3, 19.1, 20.5,
2
0
17
4
3
22.0, 36.7, 39.4, 42.2, 42.5, 51.7, 52.2, 56.4, 60.2, 60.8,
122.6, 123.1, 125.2, 125.7, 125.9, 127.5, 128.7, 132.1, 144.2,
6
2
d: Yield 20%; colorless crystals (ethyl acetate); mp 205–
2
1 1
þ
87), 400 (19), 368 (40), 327 (45), 295 (51), 239 (100). Found:
068C; IR (KBr) 2951, 1726, 1437 cm ; H NMR (CDCl3)
145.6, 171.1, 172.2, 172.7; MS m/z (rel. intensity) 432 (M ,
d 1.28 (t, 3H, J¼7.1 Hz, CH ), 1.50–1.70 (m, 2H, Hb,d),
3
1
1
3
4
7
2
1
.86 (dt, 1H, J¼7.5, 1.6 Hz, H ), 2.17 (m, 1H, H ), 2.71 (dt,
m/z 432.1568. Mass calcd for C H O : 432.1566.
26 24 6
g
c
H, J¼5.6, 1.8 Hz, H ), 2.90 (dd, 1H, J¼7.5, 1.0 Hz, H ),
e
h
1
.15 (br s, 1H, H ), 3.55 (s, 3H, CH ), 3.91 (s, 3H, CH ),
3
9c: H NMR (CDCl ) d 1.29 (t, 3H, J¼7.1 Hz, CH ), 1.64
f
3
3
3
.16 (q, 2H, J¼7.1 Hz, CH ), 6.90–7.40 (m, 3H, Ar), 7.42–
(m, 1H, H ), 1.70 (t, 1H, J¼3.1 Hz, H ), 2.04 (dd, 1H,
g c e,h
2
d
b
1
3
.65 (m, 1H, Ar); C NMR (CDCl ) d 14.3, 19.0, 19.9,
3
J¼7.9, 1.9 Hz, H ), 2.20 (m, 1H, H ), 2.75 (m, 2H, H ),
3.30 (br s, 1H, H ), 3.51 (s, 3H, CH ), 3.94 (s, 3H, CH ),
f 3 3
1.9, 35.2, 38.6, 40.2, 44.7, 51.8, 52.1, 55.3, 59.2, 60.8,
20.8, 124.5, 125.8, 125.9, 146.9, 147.1, 171.1, 172.2,
4.16 (q, 2H, J¼7.1 Hz, CH ), 7.20–7.96 (m, 6H, Ar).
2

K. Saito et al. / Tetrahedron 58 (2002) 9081–9088
9087
3
.1.3. Reaction of diene (5d) with anthracene. By a
similar procedure as described for naphthalene, 5d (0.31 g,
.0 mmol) was treated with anthracene (0.53 g, 3.0 mmol)
in refluxing ethyl acetate (10 ml) with Pd(OAc) (0.23 g,
(100), 274 (59). Found: m/z 482.1737. Mass calcd for
C H O : 482.1722.
3
0 26 6
1
3.1.5. Reaction of diene (5d) with tropone. By a similar
procedure as described for naphthalene, 5d (0.31 g,
1.0 mmol) was treated with tropone (0.53 g, 5.0 mmol) in
refluxing acetonitrile (8 ml) with Pd(OAc)2 (0.23 g,
1.0 mmol) and NaOAc (0.41 g, 5.0 mmol) for 4 days to
afford a single isomer of product in 4% yield. 12: IR (NaCl)
2
1.0 mmol) and NaOAc (0.41 g, 5.0 mmol) for 4 days to
afford three isomers of products.
1
1
1
0a: Yield 13%; colorless crystals (ethanol); mp 148–
498C; IR (KBr) 2953, 1723 cm2 ; H NMR (CDCl ) d
1 1
3
2955, 1724, 1572 cm2 ; H NMR (CDCl ) d 1.28 (t, 3H,
1 1
.28 (t, 3H, J¼7.1 Hz, CH ), 1.68 (m, 1H, H ), 1.75 (t, 1H,
3
d
3
J¼3.1 Hz, H ), 1.90 (d, 1H, J¼7.6 Hz, H ), 2.21 (m, 1H,
J¼7.1 Hz, CH ), 1.54 (m, 1H, H ), 1.70 (m, 1H, H ), 2.05–
b
g
3
d
b
H ), 2.79 (m, 2H, H ), 3.34 (br s, 1H, H ), 3.51 (s, 3H,
c
2.17 (m, 2H, H ), 2.65 (dt, 1H, J¼6.7, 3.3 Hz, H ), 2.97
e,h
f
c,g
e
CH ), 3.97 (s, 3H, CH ), 4.14 (q, 2H, J¼7.1 Hz, CH ), 7.43
(ddd, 1H, J¼7.7, 4.3, 1.2 Hz, H ), 3.58 (s, 3H, CH ), 3.60
f 3
3
3
2
h 3
(m, 2H, Ar), 7.68 (s, 1H, Ar), 7.98 (m, 2H, Ar), 8.08 (s, 1H,
Ar), 8.29 (s, 1H, Ar), 8.40 (s, 1H, Ar); C NMR (CDCl ) d
(br s, 1H, H ), 3.89 (s, 3H, CH ), 4.14 (q, 2H, J¼7.1 Hz,
CH ), 6.97 (m, 1H, Ar), 7.09–7.21 (m, 2H, Ar), 7.51 (d, 1H,
2
1
3
3
1
3
1
5
1
1
4
4.3, 19.0, 19.2, 22.0, 32.1, 36.3, 38.3, 44.2, 51.8, 52.3,
2.9, 58.5, 60.8, 118.6, 123.1, 125.1, 125.2, 125.7, 126.8,
27.8, 128.1, 130.7, 130.9, 131.5, 131.6, 142.9, 143.6,
J¼11.0 Hz, Ar); C NMR (CDCl ) d 14.2, 18.3, 19.2, 21.5,
3
35.9, 38.5, 41.5, 44.0, 51.9, 52.6, 53.3, 60.9, 63.9, 132.1,
134.8, 136.1, 142.2, 156.4, 159.5, 170.0, 171.9, 172.5,
þ
þ
(51), 305 (96), 277 (41). Found: m/z 410.1383. Mass calcd
71.1, 171.9, 172.6; MS m/z (rel. intensity) 482 (M , 100),
51 (7), 404 (6), 377 (9), 289 (21). Found: m/z 482.1711.
182.7; MS m/z (rel. intensity) 410 (M , 100), 379 (35), 351
Mass calcd for C H O : 482.1722.
3
for C H O : 410.1359.
23 22 7
0
26
6
1
1
CH ), 1.68 (m, 1H, H ), 1.75 (m, 1H, H ), 2.02 (m, 1H, H ),
0b: Yield 4%; H NMR (CDCl ) d 1.28 (t, 3H, J¼7.1 Hz,
3.1.6. Reactions of dienes (5a–e, 7) with iodobenzene. A
mixture of 5a (0.23 g, 1.0 mmol) and iodobenzene (0.61 g,
3.0 mmol) in dry acetonitrile (6 ml) with Pd(OAc) (0.23 g,
3
3
d
b
g
2
.21 (m, 1H, H ), 2.94 (m, 1H, H ), 3.05 (m, 1H, H ), 3.50
c
e
h
2
(
s, 3H, CH ), 3.91 (br s, 1H, H ), 3.96 (s, 3H, CH ), 4.17 (q,
3
1.0 mmol), NaOAc (0.41 g, 5.0 mmol), and n-Bu NCl
4
3
f
2
H, J¼7.1 Hz, CH ), 7.43 (m, 2H, Ar), 7.80 (d, 1H,
(0.28 g, 1.0 mmol) was refluxed for 6 h under nitrogen.
An insoluble solid was removed by filtration and the filtrate
was concentrated. To the residue ethyl acetate and water
were added. The organic layer was separated and the
aqueous layer was extracted with ethyl acetate. The
combined organic solution was dried over Na SO and
2
J¼8.1 Hz, Ar), 7.86 (d, 1H, J¼8.1 Hz, Ar), 7.98 (m, 2H,
Ar), 8.25 (s, 1H, Ar), 8.38 (s, 1H, Ar).
1
1
CH ), 1.70 (m, 1H, H ), 1.74 (m, 1H, H ), 1.94 (d, 1H,
0c: Yield 3%; H NMR (CDCl ) d 1.28 (t, 3H, J¼7.1 Hz,
3
3
d
b
2
4
J¼7.6 Hz, H ), 2.20 (m, 1H, H ), 2.88 (d, 1H, J¼7.6 Hz,
concentrated. The residue was purified by column chroma-
tography (silica gel, n-hexane–ethyl acetate¼4:1) and was
recrystallized from ethanol to give 6a in 68% yield.
g
c
H ), 2.94 (m, 1H, H ), 3.47 (br s, 1H, H ), 3.51 (s, 3H, CH ),
3
h
e
f
3
2
.94 (s, 3H, CH ), 4.17 (q, 2H, J¼7.1 Hz, CH ), 7.21 (m,
3
2
H, Ar), 7.40 (m, 2H, Ar), 7.47 (d, 1H, J¼8.1 Hz, Ar), 7.84
(
m, 2H, Ar), 8.01 (d, 1H, J¼7.7 Hz, Ar).
Similar reactions were applied for dienes 5b–e and 7 to
afford compounds 6b–e and 8, respectively.
3.1.4. Reaction of diene (5d) with phenanthrene. By a
similar procedure as described for naphthalene, 5d (0.31 g,
6b: Yield 58%.
1
9
.0 mmol) was treated with phenanthrene (1.60 g,
.0 mmol) in refluxing ethyl acetate (10 ml) with
6c: Yield 79%.
Pd(OAc)2 (0.23 g, 1.0 mmol) and NaOAc (0.41 g,
5
1
1
.0 mmol) for 4 days to afford a mixture of two isomers
1a and 11b (7:3) in 8% yield. 11: IR (KBr) 2953, 1723,
437, 1308, 1181 cm ; H NMR (CDCl ) d 1.30 (t, 3H,
3
6d: Yield 73%.
2
1 1
6e: Yield 35%; colorless crystals (ethanol); mp 130–1318C;
IR (KBr) 2953, 1721 cm2 ; H NMR (CDCl ) d 1.50 (dd,
1 1
J¼7.0 Hz, CH ), 1.70 (m, 1H, H ), 1.76 (m, 1H, H ), 1.89–
3
d
b
3
1
2
3
.92 (m, 1H, H ), 2.20–2.22 (m, 1H, H ), 2.81 (m, 1H, H ),
e
1H, J¼10.2, 5.8 Hz, H ), 1.68 (s, 3H, CH ), 2.03 (dt, 1H,
g
c
d
3
.88 (m, 1H, H ), 3.32 (br s, 0.3H, H ), 3.37 (br s, 0.7H, H ),
h
J¼7.7, 1.9 Hz, H ), 2.24 (dd, 1H, J¼10.2, 4.1 Hz, H ), 2.68
f
f
g
c
.49 (s, 0.9H, CH ), 3.50 (s, 2.1H, CH ), 3.95 (s, 2.1H,
3
(dt, 1H, J¼5.8, 1.9 Hz, H ), 2.76 (dd, 1H, J¼7.7, 4.1 Hz,
3
e
CH ), 3.98 (s, 0.9H, CH ), 4.17 (q, 2H, J¼7.0 Hz, CH ),
H ), 3.45 (br s, 1H, H ), 3.55 (s, 3H, CH ), 3.67 (s, 3H, CH ),
3
3
3
2
h
f
3
7
.56 (m, 1H, Ar), 7.61–7.64 (m, 1H, Ar), 7.66 (d, 0.3H,
3.89 (s, 3H, CH ), 7.06–7.17 (m, 3H, Ar), 7.51 (d, 1H,
3
1
3
J¼8.9 Hz, Ar), 7.72 (d, 1H, J¼8.3 Hz, Ar), 7.76 (d, 0.7H,
J¼7.4 Hz, Ar); C NMR (CDCl ) d 11.4, 22.1, 23.8, 26.0,
3
J¼8.8 Hz, Ar), 7.87–7.88 (m, 1H, Ar), 8.04 (s, 0.7H, Ar),
33.3, 37.4, 39.7, 43.8, 51.7, 52.0, 52.2, 56.4, 61.3, 120.9,
124.4, 125.6, 125.9, 145.5, 147.8, 171.0, 172.8, 175.1; MS
8
0
.43 (s, 0.7H, Ar), 8.60 (d, 0.7H, J¼8.3 Hz, Ar), 8.75 (d,
1
3
þ
(57), 258 (100). Found: m/z 382.1405. Mass calcd for
.3H, J¼8.3 Hz, Ar), 8.85 (s, 0.3H, Ar); C NMR (CDCl )
m/z (rel. intensity) 382 (M , 12), 351 (18), 318 (52), 291
3
d 14.8, 19.5, 20.1, 22.5, 22.5, 34.6, 38.2, 40.1, 44.8, 45.3,
5
1
1
1
1
4
2.3, 52.8, 52.8, 55.2, 55.2, 59.4, 59.7, 61.3, 114.9, 119.1,
20.6, 123.0, 123.5, 124.8, 126.7, 126.7, 126.8, 126.8,
26.9, 127.2, 128.0, 128.9, 129.0, 129.1, 129.3, 130.7,
31.0, 131.1, 131.2, 132.4, 132.6, 145.3, 145.5, 145.6,
45.9, 171.6, 171.7, 172.4, 173.1; MS m/z (rel. intensity)
C H O : 382.1414.
22 22 6
8: Yield 60%.
3.1.7. Reactions of diene (5d) with iodoarenes. By a
similar procedure as described for iodobenzene, 5d (0.31 g,
þ
82 (M , 87), 418 (51), 377 (47), 345 (85), 317 (48), 289

9088
K. Saito et al. / Tetrahedron 58 (2002) 9081–9088
1
3
.0 mmol) was treated with 1,4-diiodobenzene (0.99 g,
mmol), 1-iodonaphthalene (0.76 g, 3.0 mmol), or 2-iodo-
Verhoeven, T. R. Organopalladium Compounds in Organic
Synthesis and in Catalysis. Comprehensive Organometallic
Chemistry; Wilkinson, G., Stone, F. G. A., Abel, E. W., Eds.;
Pergamon: Oxford, 1982; Vol. 8, pp 799–938. (d) Trost, B. M.
Tetrahedron 1977, 33, 2615–2649. (e) Tsuji, J. Tetrahedron
1986, 42, 4361–4401.
tropone (0.70 g, 3.0 mmol) to afford compounds 13, 9b, and
1
2, respectively.
13: Yield 30%; colorless crystals (n-hexane–ethyl acetate);
1
mp 177–1788C; IR (KBr) 2953, 1726 cm
2
1
;
H NMR
5. (a) Segnitz, A.; Bailey, P. M.; Maitlis, P. M. J. Chem. Soc.,
Chem. Commun. 1973, 698–699. (b) Coulson, D. R. J. Am.
Chem. Soc. 1969, 91, 200–202. (c) Green, M.; Hancock, R. I.
J. Chem. Soc. A 1967, 2054–2057. (d) Hughes, R. P.; Powell,
J. J. Organomet. Chem. 1972, 34, C51–C54. (e) Li, C.-S.;
Cheng, C.-H.; Cheng, S.-S.; Shaw, J.-S. J. Chem. Soc., Chem.
Commun. 1990, 1774–1775. (f) Li, C.-S.; Cheng, C.-H.; Liao,
F.-L.; Wang, S.-L. J. Chem. Soc., Chem. Commun. 1991,
(
1
CDCl ) d 1.28 (t, 3H, J¼7.1 Hz, CH ), 1.61 (m, 1H, H ),
3
3
d
.65 (m, 1H, H ), 1.83 (d, 1H, J¼7.8 Hz, H ), 2.15 (m, 1H,
b
g
H ), 2.68 (d, 1H, J¼5.3 Hz, H ), 2.88 (dd, 1H, J¼7.8,
c
e
4
3
.9 Hz, H ), 3.11 (br s, 1H, H ), 3.57 (s, 3H, CH ), 3.89 (s,
h f 3
H, CH ), 4.18 (q, 2H, J¼7.1 Hz, CH ), 6.91 (d, 1H,
3
2
J¼7.6 Hz, Ar), 7.43 (dd, 1H, J¼7.6, 1.9 Hz, Ar), 7.88 (d,
1
3
1
2
9
H, J¼1.9 Hz, Ar); C NMR (CDCl ) d 14.1, 18.7, 19.5,
3
1.8, 35.1, 38.2, 39.9, 44.2, 51.8, 52.2, 55.1, 59.0, 60.7,
0.7, 122.7, 133.6, 134.8, 146.6, 148.9, 170.4, 171.7, 172.4;
þ
70 (91), 300 (28). Found: m/z 508.0369. Mass calcd for
7
10–712.
6
. (a) Goldstein, M. J.; Gevirtz, A. H. Tetrahedron Lett. 1965,
4
MS m/z (rel. intensity) 508 (M , 43), 444 (100), 403 (51),
3
C H IO : 508.0377.
417–4422. (b) Alder, K.; Jacobs, G. Chem. Ber. 1953, 86,
528–1539.
1
2
2
21
6
7
8
9
. Jenner, G.; Papadopoulos, M. J. Org. Chem. 1986, 51,
5
85–589.
9
1
b: Yield 54%.
2: Yield 22%. This H NMR spectrum was coincident with
. Saito, K.; Kozaki, M.; Imai, A.; Hara, Y.; Takahashi, K. Chem.
Lett. 1994, 1769–1772.
1
. (a) Jia, C.; Lu, W.; Oyamada, J.; Kitamura, T.; Matsuda, K.;
Irie, M.; Fujiwara, Y. J. Am. Chem. Soc. 2000, 122,
that of the material obtained in the reaction of diene 5d and
tropone.
7
252–7263. (b) Jia, H.; Piao, D.; Oyamada, J.; Lu, W.;
Kitamura, T.; Fujiwara, Y. Science 2000, 287, 1992–1995.
(
(
c) Moritani, I.; Fujiwara, Y. Synthesis 1973, 524–533.
d) Fujiwara, Y.; Moritani, I.; Danno, S.; Asano, R.; Teranishi,
Acknowledgements
S. J. Am. Chem. Soc. 1969, 91, 7166–7169.
0. (a) Larock, R. C.; Yum, E. K. Tetrahedron 1996, 52,
743–2758. (b) Larock, R. C.; Yang, H.; Pace, P.; Narayanan,
We thank Dr M. Tomura, Institute for Molecular Science,
for performing elemental analyses and mass spectroscopy.
1
2
K.; Russell, C. E. Tetrahedron 1998, 54, 7343–7356. (c) Ma,
S.; Negishi, E. J. Am. Chem. Soc. 1995, 117, 6345–6357.
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