Efficient macrocyclization using methylene-tethered terminal dienes and bis(manganese(III)-enolate)s

Article abstract of DOI:10.1016/j.tet.2010.02.022

Macrocyclic compounds, which have two fused dihydrofuran rings, were synthesized with complete control by the oxidation of α,α,ω,ω-tetraaryl-α,(ω-1)-alkadienes 1_x with manganese(III)-oligomethylenebis(enolate) complexes directly formed by the reaction of the oligomethylene bis(3-oxobutanoate)s 2_y with manganese(III) acetate in situ. The oxamethylene-tethered macrodiolides 5 and 7 were also produced in good to moderate yields by a similar oxidation. The key intermediate, an electron donor-acceptor-like complex, was proposed for the efficient macrocyclization reaction.

Full text of DOI:10.1016/j.tet.2010.02.022

Tetrahedron 66 (2010) 2683–2694
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Efficient macrocyclization using methylene-tethered terminal dienes and
bis(manganese(III)-enolate)s
*
Yosuke Ito, Tomomi Yoshinaga, Hiroshi Nishino
Department of Chemistry, Graduate School of Science and Technology, Kumamoto University, Kurokami 2-39-1, Kumamoto 860-8555, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Macrocyclic compounds, which have two fused dihydrofuran rings, were synthesized with complete control
Received 15 December 2009
Received in revised form 1 February 2010
Accepted 2 February 2010
by the oxidation of a,a,u,u-tetraaryl-a,(u-1)-alkadienes 1x with manganese(III)-oligomethylenebis(enolate)
complexes directly formed by the reaction of the oligomethylene bis(3-oxobutanoate)s 2y with man-
ganese(III) acetate in situ. The oxamethylene-tethered macrodiolides 5 and 7 were also produced in good to
moderate yields by a similar oxidation. The key intermediate, an electron donor–acceptor-like complex, was
proposed for the efficient macrocyclization reaction.
Available online 10 February 2010
Keywords:
Macrocyclization
Ó 2010 Elsevier Ltd. All rights reserved.
Oxidation
Electron donor–acceptor complex
Manganese(III) acetate
Macrocyclic compounds
1. Introduction
air.9h,11 When the oxidation of
presence of the -tetraaryl-a u
b
-ketoesters was carried out in the
a,a
,u,u
,( -1)-alkadienes I (path a in
Many macrocyclic compounds have been isolated from natural
sources, some of which have significant biological activities,1 for ex-
ample, the erythromycin and rifamycin antibiotics,2 while many
macrocyclic compounds were synthesized in order to manifest
a functionality such as molecular recognition3 and metal ion trans-
port.4 Therefore, from the standpoint of the pharmaceutical interests
of the natural macrocycles5 and physicochemical properties of the
synthesized macrocyclic compounds,6 the synthesis of the func-
tionalized macrocyclic compounds and the development of the
synthetic method of the macrocycles are very attractive. In general, it
is convenient to prepare cyclic compounds using a free-radical cy-
clization reaction,7 especially, the radical-based construction of the
five and six-membered or smaller ring system is efficient. However,
most of the macrocyclic compounds are synthesized according by
ionic reactions,8 and needless to say, the synthesis of more than 10-
membered macrocycles is somewhat difficult using radical reactions.
Previously, we9a–t and other research groups9u–z developed the oxi-
dative radical cyclization using manganese(III)-enolate complexes as
the carbon radical promoter. The reaction of alkenes with 1,3-dicar-
bonyl compounds in the presence of manganese(III) acetate selec-
tively gave the corresponding 4,5-dihydrofurans at elevated
temperature9o,10 and 1,2-dioxan-3-ols at ambient temperature in
Scheme 1), the corresponding bis(dihydrofuran)s II were produced,12
while the reaction was applied the methylene-tethered bis(3-oxo-
butanoate)s in the presence of alkene to give the corresponding oli-
gomethylene bis(dihydrofurancarboxylate)s IV during the
production of the formal biradicals III (path b in Scheme 1).13a,b
Therefore, we realized that the use of both the oligomethylene-
tethered terminal dienes I and bis(3-oxobutanoate) radicals III in
the manganese(III)-oxidation system must lead to the production of
macrocyclic compounds (path c in Scheme 1). In fact, the reaction of
1,5-hexadiene with oligomethylene bis(3-oxobutanoate) was pre-
liminarily examined and the desired macrodiolide, such as V, was
obtained.13 We now report the full results of the macrocyclization
using both oligomethylene-tethered terminal dienes and
bis(3-oxobutanoate)s, optimized reaction conditions, and reaction
limitations.
2. Results and discussion
2.1. Reaction of 1,5-hexadiene 12 with bis(3-oxobutanoate) 22
in the presence of manganese(III) acetate
We initially examined the oxidation of a mixture of 1,1,6,6-tet-
raphenyl-1,5-hexadiene (12) and ethylene bis(3-oxobutanoate) (22)
with manganese(III) acetate in glacial acetic acid at 100 ꢀC under an
argon atmosphere, and fortunately the desired 12-membered mac-
rodiolide 32,2 was obtained in 40% yield together with an intractable
* Corresponding author. Tel./fax: þ81 96 342 3374.
E-mail address: nishino@sci.kumamoto-u.ac.jp (H. Nishino).
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.02.022

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Y. Ito et al. / Tetrahedron 66 (2010) 2683–2694
Tetrahedron
O O
O O
Me
O O
Me
(CH2)m
Me
OEt
O
O
Mn(OAc)3
Mn(OAc)3
path b
path a
Ph Ph
O
Me
O
Ph
Ph
O
O
O
Ph
Me
Me
Ph
Ph
O
O
Ph
O
Me
O
Ph
EtO
Mn(OAc)3
Mn(OAc)3
CO2Et
CO2Et
(CH2)n
(CH2)m
(CH2)m
(CH2)n
reflux
(n>1)
100 °C
(m>2)
EtO
Me
Ph
Ph
O
O
O
O
Me
O
O
O
Ph
Ph
Ph
Me
O
II
O
Me
I
Ph Ph
III
IV
path c
Ph
O
Me
Ph
O
O
(CH2)m
(CH2)n
?
O
O
Ph
Ph
O
O
V
Scheme 1. Strategy of the macrocyclization.
mixture (Scheme 2 and Table 1, entry 1).13a We scrutinized the re-
action conditions and ascertained that dissolved molecular oxygen
in the solvent must complicate the reaction, while the dilution
conditions were important for the macrocylization to avoid poly-
merization.13b Therefore, before the reaction, the mixture was suf-
ficiently degassed under reduced pressure for 30 min using an
ultrasonicator for exchange with an argon atmosphere. The mixture
was then heated at 100 ꢀC until the manganese(III) acetate was
completely consumed (entries 2–4). As a result, the yield of the
macrodiolide 32,2 increased to 71% (entry 5).
2.2. Manganese(III)-based oxidation of a combination of
various methylene-tethered terminal dienes 1x and
bis(3-oxobutanoate)s 2y
With the optimized conditions in hand, we applied the re-
action to a combination of much longer methylene-tethered ter-
minal dienes 1x (x¼1–28) and bis(3-oxobutanoate)s 2y (y¼2–26),
and the desired macrodiolides 3x,y were obtained in good to
moderate yields (Scheme 3 and Table 2). Although increasing the
ring size tended to decrease the yield, the difference in
the methylene chain length of the dienes 1x and the
bis(3-oxobutanoate)s 2y did not affect the yield of 3x,y. When the
combination of 15 and 24 was used, the best yield of the macro-
diolide 3x,y was achieved and the corresponding 17-membered
macrodiolide 35,4 was isolated in 86% yield (entry 9). As a result,
according to the macrocyclization reaction, the synthesis of vari-
ous sizes of macrodiolides 3x,y from the smallest (12-membered
Ph
Ph
Ph
Ph
Ph
Ph
O
Ph
Mn(OAc)3
O
O
Ph
12
Me
AcOH
100 °C
argon
Me
O
O
Me
O
O
Me
O
O O
O O
3
2,2; entry 2) to the largest (62-membered 328,26; entry 24) could
32,2
22
be accomplished. However, the reaction of the pentadiene 11 with
the bis(3-oxobutanoate) 22 to give the corresponding 11-mem-
bered macrodiolide failed (entry 1), probably due to steric
hindrance of the four neighboring phenyl groups.
Scheme 2.
Table 1
Reaction of 1,5-hexadiene 12 with bis(3-oxobutanoate) 22 under various
concentrationa
Entry
AcOH/mL
Concn of 12/mM
T/min
3
2,2/%b
Ph
Ph
Ph
(CH2)x
(CH2)x
1
2
3
4
5
30
60
150
250
500
33.3
16.7
3.3
2.0
1.0
45
60
30
40
25
40
51
64
68
71
Ph
Ph
Ph
Ph
Ph
Mn(OAc)3
O
O
1x
AcOH
100 °C
argon
Me
Me
O
Me
O
O
Me
O
O
O
(CH2)y
(CH2)y
a
The reaction was carried out at the molar ratio of 12 (0.5 mmol):22:
Mn(OAc)3¼1:1.5:7 in acetic acid at 100 ꢀC after exchange with an argon atmosphere by
ultrasonication except for entry 1.
O O
O O
x = 2-28
y = 2-26
3x,y
2y
b
Scheme 3.
Isolated yield based on 12.

Y. Ito et al. / Tetrahedron 66 (2010) 2683–2694
2685
Table 2
Table 3
Reaction of dienes 1x with di(3-oxobutanoate)s 2y in the presence of manganese(III)
Reaction of 1x with 4y in the presence of manganese(III) acetatea
acetatea
Entry
x
y
1x:4y:Mn(III)b
T/min
5
x,y/%c
Ring size
Entry
x
y
1x:2y:Mn(III)b
T/min
3
x,y/%c
0
Ring size
1
2
3
4
5
6
7
8
9
1
2
3
4
2
3
4
5
6
2
2
2
2
3
3
3
3
3
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
60
50
50
30
80
60
70
80
60
27
71
77
86
45
56
68
55
56
14
15
16
17
18
19
20
21
22
1
2
3
4
5
6
7
8
1
2
2
2
3
4
4
5
5
6
6
6
6
8
8
8
8
2
2
3
4
3
2
3
3
4
4
6
1:1.5:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
60
40
50
40
50
70
60
40
80
80
25
18
21
33
24
15
35
60
21
21
46
36
32
82
11
12
13
14
14
14
15
16
17
18
20
24
26
22
26
28
36
30
34
36
44
46
42
62
68
64
66
67
76
74
57
86
59
60
53
57
54
46
49
49
40
50
50
50
36
40
22
9
a
The reaction was carried out in acetic acid (0.2 mM for 1x) at 100 ꢀC under an
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
argon atmosphere.
b
Molar ratio.
Isolated yield based on 1x.
10
12
6
10
12
20
6
10
12
20
20
6
c
conditions and the desired macrodiolides 7x,y were produced in
moderate yields (Scheme 5 and Table 4). It seemed that the
oxamethylene-chain length of 6x and 4y might be important since the
yield of 7 decreased in the reaction of the shortest 60 with the longer
4y (y¼3 and 4). In addition, the oxamethylene-tethered alkadienes 6x
were longer, the ionization potential of 6x was lower, and therefore,
the direct oxidation of 6x with manganese(III) acetate must occur
since the decomposed fragments were isolated instead of the
recovery of 6x.
16
16
16
16
18
28
28
26
a
The reaction was carried out in acetic acid (0.2 mM for 1x) at 100 ꢀC under an
Ph
argon atmosphere.
b
O
Molar ratio.
Isolated yield based on 1x.
Ph
Ph
O
O
c
x
(CH2)2
O
O
O
Ph
Ph
Ph
x
Ph
Ph
Mn(OAc)3
6x
O
O
2.3. Manganese(III)-based oxidation of a combination of
various oxamethylene-tethered terminal dienes 6x and bis
(3-oxobutanoate)s 4y
AcOH
100 °C
argon
O
O
Me
Me
O
O
O
(CH2)2
O
y
Me
y
Me
O
O
4y
x = 0-4
y = 1-4
7x,y
The results encouraged us to investigate a similar reaction
using the oxamethylene-tethered terminal dienes 6x and
Scheme 5.
bis(3-oxobutanoate)s 4y, which seemed to produce
a crown
ether-type macrodiolide. The oxamethylene-tethered bis(3-oxobu-
tanoate)s 4y (y¼1–4) were prepared by the reaction of the corre-
sponding glycols with diketene. First of all, we examined the reaction
of 1,1,8,8-tetraphenyl-1,7-octadiene (14) with 3-oxapentamethylene
bis(3-oxobutanoate) (42) (Scheme 4). As a result, the expected mac-
rocyclization occurred and the desired 17-membered macrodiolide
Table 4
Reaction of 6x with 4y in the presence of manganese(III) acetatea
Entry
x
y
6x:4y:Mn(III)b
T/min
7
x,y/%c
Ring size
1
2
3
4
5
6
7
8
0
0
0
0
1
1
1
1
2
2
2
2
3
3
3
3
4
4
4
4
1
2
3
4
1
2
3
4
1
2
3
4
1
2
3
4
1
2
3
4
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.5:7
1:1.3:6
1:1.3:6
1:1.3:6
1:1.5:7
1:1.3:7
1:1.3:7
1:1.5:7
1:1.3:7
1:1.3:7
1:1.3:7
1:1.3:7
60
40
60
40
30
50
60
120
30
40
40
40
50
60
40
30
40
70
150
30
51
67
37
24
66
63
62
29
34
35
33
27
42
42
35
39
40
44
42
30
13
16
19
22
16
19
22
25
19
22
25
28
22
25
28
31
25
28
31
34
54,2 was produced in 86% yield (Table 3, entry 4). A similar reaction of
other terminal alkadienes 1x (x¼1–6) with bis(3-oxobutanoate) 4y
(y¼2 and 3) also gave the corresponding macrodiolides 5x,y in good to
moderate yields (Table 3). The pentadiene 11 afforded the 14-mem-
bered macrodiolide 51,2 in only 27% yield probably due to the crow-
ded tetraphenyl groups.
9
10
11
12
13
14
15
16
17
18
19
20
Ph
Ph
Ph
(CH2)x
(CH2)x
Ph
Ph
Ph
Ph
Ph
1x
Mn(OAc)3
O
O
O
O
AcOH
100 °C
argon
O
y
Me
Me
Me
O
O
O
O
(CH2)2
Me
O
y
O
O
x = 1-6
y = 2,3
4y
5x,y
Scheme 4.
a
The reaction was carried out in acetic acid (0.2 mM for 6x) at 100 ꢀC under an
argon atmosphere.
b
Molar ratio.
Isolated yield based on 6x.
Since the combinationof the alkadienes 1x and the oxamethylene-
tethered bis(3-oxobutanoate)s 4y succeeded for the macro-
cyclization, we next examined the combination of both the
oxamethylene-tethered 6x (x¼0–4) and 4y (y¼1–4) in order to syn-
thesize crown ether-type macrodiolides. The oxamethylene-tethered
terminal dienes 6x (x¼1–4) were prepared by the Williamson ether
synthesis of the corresponding glycols with 1,1-diphenyl-3-bromo-
propene. The reaction was carried out under the optimized
c
2.4. Structure determination of macrodiolides
The isolated macrodioides 3, 5, and 7 were characterized by
a spectroscopic method, combustion analysis as well as FABMS
spectrometry, and X-ray crystallography. The 13C NMR spectrum

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Y. Ito et al. / Tetrahedron 66 (2010) 2683–2694
contained peaks assigned to the ester carbonyl, all the dihydrofuran
ring carbons, and the methylene carbon attached to the ester ox-
ygen appeared as two slightly different peaks, due to the diaster-
eomixture of the macrodiolides that contained two asymmetric
carbons. For example, in the 13C NMR spectrum of the 20-mem-
bered macrodiolide 36,6, the peaks assigned to the ester carbonyl
9-decenyldihydrofurancarboxylate 8 (28%)16 and the unchanged
diene 18 (26%) (see Experimental section). This suggested that the
macrocyclization should follow a stepwise process. Accordingly, in
order to demonstrate the stepwise process, the intermediate dihy-
drofuran 8 was alternatively prepared by the manganese(III)-
oxidation of the diene 18 with THP-protected hexamethylene
butanoate 9 followed by esterification with diketene (Scheme 6). The
reaction of 8 using a stoichiometric amount of manganese(III) ace-
tate actually gave the macrodiolide 38,6 in 78% yield.
appeared at
the dihydrofuran ring at
48.5, the methylene carbons attached to the ester oxygens at
d
166.7 and 166.5, the sp2, and the methine carbons of
166.1 and 166.0,108.6 and 108.4, 48.6 and
63.3
d
d
and 63.2 ppm, respectively. However, this phenomenon dis-
appeared in the large macrodiolides of more than 26 members. In
addition, energy calculations of the meso- and DL-macrodiolides
were performed by the MOPAC PM3 program;14 however, the for-
mation energies were not very different because of the large
macrocyclic rings. Fortunately, the macrodiolides 54,2, 53,3, and 70,3
crystallized from dichloromethane/hexane to provide single crys-
tals, which were measured by X-ray diffraction. As a result, it was
confirmed that the macrocyclic compounds had two fused dihy-
drofuran rings, and the two asymmetric carbons of 54,2, 53,3 showed
a meso-configuration and those of 70,3 had a DL-configuration (Fig. 1
and see Experimental).
The remaining question was why the intermediate dihydrofuran
such as 8 smoothly underwent an intramolecular cyclization to afford
large macrocyclic compounds such as the 62-membered macro-
diolide 328,26. For example, when the dihydrofuran 8 was produced
by the reaction of the diene 18 with bis(3-oxobutanoate) 26 during
the first stage, each reaction site during the next intramolecular
cyclization should be quite far due to the steric repulsion between the
decenyl-side chain and the oxadioxoundecyloxycarbonyl-side chain
of 8. This was also supported by the MM2 calculation
(see Supplementary data).14 However, in order to undergo the
intramolecular cyclization during the second stage, each reaction site
must be closer. Recently, we proposed a unique electron donor–ac-
ceptor-like the manganese(III)-enolate intermediate complex
(EDA complex) in the manganese(III) oxidation system.17 The donor
alkene would undergo a complex formation with the acceptor eno-
late in the inner sphere of the oxygen-centered manganese(III)-tri-
angle complex and one-electron-transfer oxidation would result in
the carbon–carbon bond formation and finally produce the dihy-
drofuran. Hence, both the reaction sites of the dihydrofuran 8 should
be in close proximity by the formation of a similar intramolecular
EDA complex such as A in Scheme 7, which seemed to easilycause the
oxidative intramolecular cyclization to give radical B, and the mac-
rodiolide 3 was finally produced via the oxidative dihydrofuranation
reaction (Scheme 7). The formation of other macrodiolides 5 and 7
could also be explained in a similar manner.
3. Conclusion
We have developed a facile and convenient synthesis of mac-
rocyclic compounds using the manganese(III)-based oxidative
radical cyclization. We guarantee the synthesis of macrodiolides
from 12 to 62 members having two fused dihydrofurans. We also
demonstrated that the macrocyclization using the methylene-
tethered terminal dienes and bis(3-oxobutanoate)s proceeded
according to a two-step process. In addition to the dilution condi-
tions from the standpoint of the manganese(III)-based macro-
cyclization, the formation of the EDA complex A during the reaction
of the intermediate dihydrofuran such as 8 with manganese(III)
acetate could play an important role in the manganese(III)-based
macrocyclization. Furthermore, the balance of the chain length of
the dienes and bis(3-oxobutanoate)s was also important for the
standpoint of the yield.
O
O
O
H
O
H
O
Me
Me
O
O
Ph Ph
Ph Ph
Figure 1. ORTEP drawing of meso-macrodiolide 54,2
.
2.5. Mechanism of the macrocyclization
The mechanism for the formation of the dihydrofurans by the
manganese(III)-based oxidation of alkenes with -diketoesters could
4. Experimental
4.1. General
b
be explained by the well-known oxidation mechanism.15,16 Hence
the manganese(III)-bis(enolate) complexes would be formed by the
reaction of the bis(3-oxobutanoate)s 2y with manganese(III) acetate
in situ, and then undergo a one-electron-transfer oxidation to give
the formal 3-oxobutanoate biradical such as III in Scheme 1, from
which the double electrophilic attack on the terminal dienes 1x
would provide the macrodiolides 3x,y via the subsequent oxidation
and deprotonation. However, when the reaction of dodecadiene 18
with hexamethylene bis(3-oxobutanoate) 26 was carried out using
a half stoichiometric amount of manganese(III) acetate, the oxidant
was completely consumed within 5 min and the corresponding
macrodiolide 38,6 was produced only in 14% yield together with
The melting points are uncorrected. The NMR spectra were
measured at 300 MHz for 1H and at 75 Hz for 13C at 400 MHz for
1H and at 100 Hz for 13C with tetramethylsilane as the internal
standard. The chemical shifts are reported in Ô values (ppm) and
the coupling constants in Hertz. The IR spectral data are expressed
in cmꢁ1. The EIMS spectra were recorded at the ionizing voltage of
70 eV. The high-resolution mass spectra were measured at the
Institute for Materials Chemistry and Engineering, Kyushu Uni-
versity, Fukuoka, Japan, and the Analytical Center of Kumamoto
University, Kumamoto, Japan. The elemental analyses were also

Y. Ito et al. / Tetrahedron 66 (2010) 2683–2694
2687
Ph
Ph
Ph Ph
Ph
Ph
O O
Ph
Ph
Me
O
O O
Me
Mn(OAc)3
18
O
Me
Me
O
O
O O
O
AcOH
100 °C
argon
-Mn(II)
III
O
O
Me
Me
O O
Mn
O
O
26
III
III
O O
Mn
Mn
Mn(III)
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Mn(OAc)3
-H
O
O
O
O
H
AcOH
100 °C
argon
(78%)
O
O
Me
O
O
O
O
Me
Me
Me
Me
Me
O
O
O
O
O O
O O
38,6
8
dry THF, rt, 24 h
diketene
imidazole (66%)
Alternative synthesis
Ph
Ph
Ph
Ph
18
Me
O
THP
O
O
Mn(OAc)3
AcOH
O
O
OH
O O
Me
100 °C
argon
9
10
(59%)
Scheme 6.
Ph
Ph
Ph
III
Ph Ph
O
Ph Ph
O
Ph
Mn(OAc)3
-Mn(II)
Mn(III)
Mn
Me
O
III
8
3
III O Mn
Mn
O
H
Me
-H
Me
Me
-Mn(II)
O
O
O
O
O
O
O
O
B:
A:
= methylene bridge
= methylene bridge
Scheme 7.
performed at the Analytical Center of Kumamoto University,
Kumamoto, Japan.
4.3. General procedure for the manganese(III)-based
oxidation of terminal dienes 1x and 6x with bis
(3-oxobutanoate)s 2y and 4y
4.2. Materials
To a solution of the terminal alkadiene 1 or 6 (0.2 mmol) and
bis(3-oxobutanoate) 2 or 4 (0.26 mmol) in glacial acetic acid
(100 mL), manganese(III) acetate dehydrate (1.4 mmol) was added
and the mixture was degassed under reduced pressure for 30 min
using an ultrasonicator for exchange with an argon atmosphere. The
mixture was then heated at 100 ꢀC under an argon atmosphere for
the period mentioned in the tables until the brown color of man-
ganese(III) disappeared. The color typically turned a transparent
yellow. The solvent was removed in vacuo, and the residue was
triturated with 2 M HCl (20 mL), and then extracted with CHCl3
(20 mLꢂ3). The combined extracts were washed with a saturated
aqueous solution of NaHCO3 (30 mL) and water, and then concen-
trated to dryness. The crude products were separated by silica gel TLC
Manganese(III) acetate dihydrate, Mn(OAc)3$2H2O, was pre-
pared according to a literature method.9 The terminal alkadienes
1x were synthesized by the reaction of the corresponding
1,u-alkanedicarboxylates with phenylmagnesium bromide fol-
lowed by acid-catalyzed dehydration. The oxamethylene-tethered
terminal dienes 6x were prepared by the Williamson ether syn-
thesis of the corresponding glycols with 1,1-diphenyl-3-bromo-
propene, which was synthesized by the bromination of
1,1-diphenylpropene. The bis(3-oxobutanoate)s 2y and 4y were
prepared by the esterification of the corresponding 1,u-alka-
nediols or glycols with diketene. Commercially available glacial
acetic acid was used as received.

2688
Y. Ito et al. / Tetrahedron 66 (2010) 2683–2694
(Wako B-10 or Whatman K6F 60A) while eluting with CHCl3, CHCl3/
MeOH, or Et2O/hexane. The analytical samples were further purified
by recrystallization from the solvent specified in parentheses except
for the amorphous products. The molar ratio and product yields are
summarized in Tables 1–4. The specific details are given below. The
189–191 ꢀC; IR (CHCl3)
(300 MHz, CDCl3) 7.59–7.02 (20H, m), 4.57–4.36 (2H, m), 4.20–
3.96 (2H, m), 3.88–3.73 (2H, m), 2.34–2.17 (6H, m), 2.10–1.88 (2H,
m), 1.46–0.50 (8H, m); 13C NMR (75 MHz, CDCl3)
166.9, 166.4,
165.9, 165.8, 145.4, 145.2, 140.9, 140.8, 128.12, 128.07, 127.7, 127.0,
126.9, 126.6, 126.5, 126.2, 126.0, 108.6, 107.6, 95.4, 95.0, 59.8, 59.4,
48.5, 47.7, 31.4, 30.1, 26.5, 26.0, 24.0, 14.5, 14.4. Anal. Calcd for
C43H42O6: C, 78.87; H, 6.47. Found: C, 78.83; H, 6.50.
n
1699 (C]O), 1650 (C]C); 1H NMR
d
d
data were shown as a diasteromixture except for 71,1
.
4.3.1. 9,18-Dimethyl-3,6,10,17-tetraoxa-2,7-dioxo-11,11,16,16-tetra-
phenyltricyclo[13.3.0.08,12]octadeca-8,18-diene (32,2). Diastereomer
ratio, 43:57. Colorless microcrystals (from CH2Cl2/hexane); mp
4.3.7. 10,22-Dimethyl-3,7,11,21-tetraoxa-2,8-dioxo-12,12,20,20-tet-
197–199 ꢀC (lit.13a mp 197–199 ꢀC); IR (CHCl3)
n
1699 (C]O), 1648
7.36–6.88 (20H, m), 4.79–4.09
(4H, m), 3.96–3.52 (2H, m), 2.38–2.14 (6H, m), 1.35–0.60 (4H, m);
13C NMR (75 MHz, CDCl3)
166.5, 165.6, 145.2, 141.0, 128.1, 127.8,
raphenyltricyclo[17.3.0.09,13]icosa-9,22-diene (35,3). Diastereomer
(C]C); 1H NMR (300 MHz, CDCl3)
d
ratio, 43:57. Colorless amorphous; IR (CHCl3)
(C]C); 1H NMR (300 MHz, CDCl3)
7.53–7.12 (20H, m), 4.53–4.08
(4H, m), 3.79–3.77 (2H, m), 2.29 (3H, s), 2.26 (3H, s), 2.01–0.63
(12H, m); 13C NMR (75 MHz, CDCl3)
166.9, 166.5, 165.9, 145.4,
n 1693 (C]O), 1647
d
d
127.6,126.9,126.6,126.3,107.8, 94.9, 60.9, 51.2, 26.8,14.4; FABMS m/
z (rel intensity), 613 (100, MþH). Anal. Calcd for C40H36O6: C, 78.41;
H, 5.92. Found: C, 78.32; H, 6.03.
d
145.2, 140.84, 140.78, 128.5, 128.09, 128.06, 127.6, 127.0, 126.9,
126.7, 126.5, 126.2, 126.1, 108.3, 107.6, 95.2, 95.0, 59.2, 58.8, 49.1,
48.2, 31.3, 30.1, 28.2, 27.94, 27.69, 24.8, 24.2, 14.5, 14.3. FAB HRMS
(acetone/NBA) calcd for C44H44O6 668.3138 (Mþ). Found
668.3083.
4.3.2. 10,19-Dimethyl-3,7,11,18-tetraoxa-2,8-dioxo-12,12,17,17-tetra-
phenyltricyclo[14.3.0.09,13]nonadeca-9,19-diene (32,3). Colorless mi-
crocrystals (from CH2Cl2/hexane); mp 259–261 ꢀC (lit.13a mp
259–260 ꢀC); IR (CHCl3)
(300 MHz, CDCl3)
3.85–3.54 (2H, m), 2.40–2.20 (6H, m), 2.11–1.85 (2H, m), 1.39–0.63
(4H, m); 13C NMR (75 MHz, CDCl3)
167.3, 166.1, 145.1, 141.0, 128.1,
n
1693 (C]O), 1645 (C]C); 1H NMR
4.3.8. 11,23-Dimethyl-3,8,12,22-tetraoxa-2,9-dioxo-13,13,21,21-tetra-
phenyltricyclo[18.3.0.010,14]tricosa-10,23-diene (35,4). Diastereomer
ratio, 41:59. Colorless microcrystals (from CH2Cl2/hexane); mp
d
7.60–6.85 (20H, m), 4.78–4.08 (4H, m),
d
127–129 ꢀC; IR (CHCl3)
(300 MHz, CDCl3)
3.81–3.58 (2H, m), 2.34–2.21 (6H, m), 1.89–1.64 (2H, m), 1.31–0.57
(10H, m); 13C NMR (75 MHz, CDCl3)
167.10, 167.01, 166.0, 165.9,
n
1700 (C]O), 1648 (C]C); 1H NMR
127.8,127.6,126.9, 126.7,126.1,107.6, 95.2, 63.2, 49.3, 27.9, 27.6, 14.5.
Anal. Calcd for C41H38O6: C, 78.57; H, 6.11. Found: C, 78.72; H, 6.17.
d 7.62–7.02 (20H, m), 4.48–3.81 (4H, m),
d
4.3.3. 11,20-Dimethyl-3,8,12,19-tetraoxa-2,9-dioxo-13,13,18,18-tetra-
phenyltricyclo[15.3.0.010,14]icosa-10,20-diene (32,4). Diastereomer
ratio, 48:52. Colorless microcrystals (from CH2Cl2/hexane); mp
145.2, 145.0, 140.8, 140.7, 128.0, 127.62, 127.58, 127.1, 127.0, 126.8,
126.6,126.3,126.2,108.5, 108.1, 95.4, 95.3, 63.1, 62.7, 48.6, 48.4, 32.5,
32.2, 29.7, 26.9, 26.0, 25.4, 25.35, 14.5, 14.4. FAB HRMS (acetone/
NBA) calcd for C45H46O6 682.3294 (Mþ). Found 682.3285.
125–128 ꢀC (lit.13a mp 124–126 ꢀC); IR (CHCl3)
n
1686 (C]O), 1643
(C]C); 1H NMR (300 MHz, CDCl3)
d 7.54–6.86 (20H, m),
4.39–4.25 (4H, m), 3.67–3.63 (2H, m), 2.29–2.16 (6H, m),
4.3.9. 11,24-Dimethyl-3,8,12,23-tetraoxa-2,9-dioxo-13,13,22,22-tet-
ra p h e nyl t r i c yc l o [ 19 . 3 . 0 . 01 0 , 14 ] t e t ra c o s a - 10 , 24 - d i e n e
(36,4). Diastereomer ratio, 50:50. Colorless microcrystals
1.90–1.80 (4H, m), 1.42–0.81 (4H, m); 13C NMR (75 MHz, CDCl3)
d
165.9, 165.7, 145.5, 141.1, 128.0, 127.8, 127.6, 126.8, 126.5, 126.1,
107.8, 95.2, 62.8, 50.3, 27.6, 26.1, 14.7. Anal. Calcd for C42H40O6: C,
78.73; H, 6.29. Found: C, 78.35; H, 6.16.
(from CH2Cl2/hexane); mp 117–119 ꢀC; IR (CHCl3)
1648 (C]C); 1H NMR (300 MHz, CDCl3)
4.43–3.89 (4H, m), 3.80–3.65 (2H, m), 2.34–2.20 (6H, m), 1.82–1.65
(2H, m), 1.39–0.70 (12H, m); 13C NMR (75 MHz, CDCl3)
166.9,
166.8, 165.9, 165.8, 145.2, 145.1, 140.8, 140.7, 128.0, 127.7, 127.6,
127.0, 126.9, 126.7, 126.2, 108.5, 108.1, 95.28, 95.27, 63.0, 62.9, 49.0,
48.5, 32.1, 31.8, 28.9, 28.8, 26.4, 25.8, 25.7, 25.5, 14.44, 14.40. FAB
HRMS (acetone/NBA/NaI) calcd for C46H48O6Na 719.3374 (MþNa).
Found 719.3349.
n
1699 (C]O),
d
7.64–7.09 (20H, m),
4.3.4. 10,20-Dimethyl-3,7,11,19-tetraoxa-2,8-dioxo-12,12,18,18-tetra-
phenyltricyclo[15.3.0.09,13]icosa-9,20-diene (33,3). Diastereomer ratio,
41:59. Colorless microcrystals (from CH2Cl2/hexane); mp 144–146 ꢀC;
d
IR (CHCl3)
7.54–7.11 (20H, m), 4.57–4.36 (2H, m), 4.23–3.98 (2H, m), 3.88–3.73
(2H, m), 2.35–2.18 (6H, m), 2.10–1.86 (2H, m), 1.55–0.50 (6H, m); 13C
NMR (75 MHz, CDCl3) 166.9, 166.4, 165.9, 165.8, 145.4, 145.2, 140.9,
n
1699 (C]O), 1648 (C]C); 1H NMR (300 MHz, CDCl3)
d
d
140.8, 128.1, 128.1, 127.7, 127.0, 126.9, 126.6, 126.4, 126.2, 126.0, 108.5,
107.6, 95.4, 95.0, 59.8, 59.4, 48.5, 47.7, 31.4, 30.1, 26.0, 24.0, 14.5, 14.4.
Anal. Calcd for C42H40O6: C, 78.73; H, 6.29. FAB HRMS (acetone/NBA)
calcd for C42H40O6 640.2825 (Mþ). Found 640.2811.
4.3.10. 13,26-Dimethyl-3,10,14,25-tetraoxa-2,11-dioxo-15,15,24,24-
tetraphenyltricyclo[21.3.0.012 ,16 ]hexacosa-12,26-diene
(36,6). Diastereomer ratio, 47:53. Rf¼0.27 (CHCl3); colorless amor-
phous; IR (CHCl3)
n
1690 (C]O), 1647 (C]C); 1H NMR (300 MHz,
CDCl3) 7.53–7.19 (20H, m), 4.38–4.24 (2H, m), 4.00–3.90 (2H, m),
3.73 (2H, m), 2.29 (3H, s), 2.27 (3H, s), 1.64–0.82 (20H, m); 13C NMR
(75 MHz, CDCl3Ô) 166.7, 166.5, 166.1, 166.0, 145.1, 140.8, 128.1, 127.7,
127.6, 127.0, 126.83, 126.75, 126.3, 126.2, 108.6, 108.4, 95.2, 63.3,
63.1, 48.6, 48.5, 32.4, 32.2, 30.0, 29.0, 26.9, 26.7, 26.2, 26.1, 14.4. FAB
HRMS (acetone/NBA) calcd for C48H53O6 725.3842 (MþH). Found
725.3821.
4.3.5. 9,20-Dimethyl-3,6,10,19-tetraoxa-2,7-dioxo-11,11,18,18-tetra-
phenyltricyclo[15.3.0.08,12]icosa-8,20-diene (34,2). Diastereomer ratio,
41:59. Colorless microcrystals (from CH2Cl2/hexane); mp 225–
228 ꢀC; IR (CHCl3)
CDCl3)
3.81–3.68 (2H, m), 2.37–2.24 (6H, m), 1.35–0.50 (8H, m); 13C NMR
(75 MHz, CDCl3) 167.8, 167.5, 165.7, 165.4, 145.1, 140.8, 140.7, 128.1,
n
1693 (C]O), 1643 (C]C); 1H NMR (300 MHz,
d
7.55–7.15 (20H, m), 4.64–4.50 (2H, m), 4.24–4.10 (2H, m),
d
127.8, 127.7, 127.1, 126.8, 126.6, 126.3, 126.2, 108.5, 107.8, 95.6, 95.4,
61.6, 61.3, 48.6, 48.3, 31.6, 31.3, 26.4, 25.2, 14.43, 14.37; FABMS m/z
(rel intensity), 641 (100, MþH). Anal. Calcd for C42H40O6: C, 78.73; H,
6.29. Found: C, 78.55; H, 6.46.
4.3.11. 17,30-Dimethyl-3,14,18,29-tetraoxa-2,15-dioxo-19,19,28,28-
tetraphenyltricyclo[23.3.0.012 ,16 ]triaconta-16,30-diene
(36,10). Rf¼0.59 (CHCl3); colorless amorphous; IR (CHCl3)
n 1687
(C]O), 1647 (C]C); 1H NMR (300 MHz, CDCl3Ô) 7.52–7.16 (20H,
m), 4.21 (2H, m), 4.00 (2H, m), 3.68 (2H, m), 2.27 (6H, m), 1.61–0.56
(28H, m); 13C NMR (75 MHz, CDCl3Ô) 166.5, 166.4, 166.2, 166.1,
145.3, 140.8, 128.0, 127.6, 127.5, 127.0, 126.8, 127.7, 126.22, 126.17,
108.1, 95.0, 63.3, 49.0, 48.9, 31.8, 29.9, 29.7, 29.62, 29.57, 28.9, 26.8,
4.3.6. 10,21-Dimethyl-3,7,11,20-tetraoxa-2,8-dioxo-12,12,19,19-tetra-
phenyltricyclo[16.3.0.09,13]henicosa-9,21-diene (34,3). Diastereomer
ratio, 41:59. Colorless microcrystals (from CH2Cl2/hexane); mp

Y. Ito et al. / Tetrahedron 66 (2010) 2683–2694
2689
26.7, 26.4, 26.3, 14.4, 14.3. FAB HRMS (acetone/NBA) calcd for
C52H60O6 780.4390 (Mþ). Found 780.4332.
29.2, 29.1, 28.9, 28.8, 25.9, 25.8, 14.4. FAB HRMS (acetone/NBA)
calcd for C58H72O6 864.5329 (Mþ). Found 864.5263.
4.3.12. 19,32-Dimethyl-3,16,20,31-tetraoxa-2,17-dioxo-21,21,30,30-
tetraphenyltricyclo[27.3.0.018,22]dotriaconta-18,32-diene
4.3.18. 17,40-Dimethyl-3,14,18,39-tetraoxa-2,15-dioxo-19,19,38,38-
tetraphenyltricyclo[35.3.0.016 , 2 0 ]tetraconta-16,40-diene
(36,12). Rf¼0.61 (CHCl3); colorless amorphous; IR (CHCl3)
n
1690
(316,10). Rf¼0.80 (CHCl3); colorless amorphous; IR (CHCl3)
n 1686
(C]O), 1647 (C]C); 1H NMR (300 MHz, CDCl3Ô) 7.57–7.07 (20H,
m), 4.22–4.13 (2H, m), 4.03–3.96 (2H, m), 3.68 (2H, m), 2.27
(6H, s), 1.61–0.55 (32H, m); 13C NMR (75 MHz, CDCl3Ô) 166.3,
166.3, 166.1, 145.3, 140.8, 127.99, 127.61, 127.57, 127.02, 126.79,
126.75, 126.2, 108.3, 95.1, 63.4, 63.3, 48.8, 31.9, 29.6, 29.1, 29.06,
29.0, 28.9, 28.6, 26.64, 26.58, 26.02, 25.98, 14.4. FAB HRMS (ace-
tone/NBA/NaI) calcd for C54H64O6Na 831.4601 (MþþNa). Found
831.4653.
(C]O), 1647 (C]C); 1H NMR (300 MHz, CDCl3Ô) 7.47–7.12 (20H,
m), 4.11–4.05 (2H, m), 3.98–3.92 (2H, m), 3.69 (2H, t, J¼5.5 Hz), 2.20
(6H, m), 1.60–0.87 (48H, m); 13C NMR (75 MHz, CDCl3Ô) 166.2,
166.1, 145.3, 140.9, 128.0, 127.6, 127.0, 126.7, 126.2, 108.4, 95.1, 63.6,
48.7, 31.8, 29.7, 29.5, 29.4, 29.2, 29.1, 28.9, 26.3, 26.1, 14.5. FAB HRMS
(acetone/NBA) calcd for C62H80O6 920.5955 (Mþ). Found 920.5958.
4.3.19. 19,42-Dimethyl-3,16,20,41-tetraoxa-2,17-dioxo-21,21,40,40-
tetraphenyltricyclo[37.3.0.018,22]dotetraconta-18,42-diene
4.3.13. 13,28-Dimethyl-3,10,14,27-tetraoxa-2,11-dioxo-15,15,26,26-
tetraphenyltricyclo[23.3.0.012 ,16 ]octacosa-12,28-diene
(38,6). Diastereomer ratio, 49:51. Rf¼0.24 (CHCl3); colorless
(316,12). Rf¼0.78 (CHCl3); colorless amorphous; IR (CHCl3)
n 1686
(C]O), 1647 (C]C); 1H NMR (300 MHz, CDCl3Ô) 7.54–7.20 (20H,
m), 4.20–4.15 (2H, m), 4.03–3.97 (2H, m), 3.74 (2H, m), 2.28 (6H, m),
1.64–0.94 (52H, m); 13C NMR (75 MHz, CDCl3Ô) 166.4, 166.1, 145.4,
140.9, 128.1, 127.7, 127.0, 126.68, 126.3, 108.4, 95.1, 63.6, 48.8, 31.9,
29.9, 29.6, 29.5, 29.3, 28.9, 26.4, 14.5. FAB HRMS (acetone/NBA)
calcd for C64H84O6 948.6268 (Mþ). Found 948.6199.
amorphous; IR (CHCl3)
n
1690 (C]O), 1647 (C]C); 1H NMR
(300 MHz, CDCl3Ô) 7.53–7.19 (20H, m), 4.30–4.21 (2H, m), 4.02–
3.92 (2H, m), 3.73 (2H, m), 2.28 (6H, s), 1.66–0.81 (24H, m); 13C
NMR (75 MHz, CDCl3Ô) 166.64, 166.56, 166.1, 166.0, 145.2, 140.9,
128.0, 127.6, 127.0, 126.8, 126.7, 126.3, 126.2, 108.43, 108.37, 95.2,
63.3, 48.8, 48.7, 32.1, 29.7, 29.1, 28.9, 26.6, 26.4, 26.0, 14.4. FAB
HRMS (acetone/NBA) calcd for C50H56O6 752.4077 (Mþ). Found
752.4027.
4.3.20. 27,50-Dimethyl-3,24,28,49-tetraoxa-2,25-dioxo-29,29,48,48-
tetraphenyltricyclo[45.3.0.026, 30]pentaconta-26,50-diene
(316,20). Rf¼0.59 (CHCl3:hexane¼8:2 v/v); colorless amorphous; IR
(CHCl3) n
1686 (C]O),1647 (C]C); 1H NMR (300 MHz, CDCl3Ô) 7.47–
4.3.14. 17,32-Dimethyl-3,14,18,31-tetraoxa-2,15-dioxo-19,19,30,30-
tetraphenyltricyclo[27.3.0.016,20]dotriaconta-16,32-diene
7.12 (20H, m), 4.13–4.10 (2H, m), 3.95–3.93 (2H, m), 3.68 (2H, m), 2.20
(6H, m), 1.56–0.85 (68H, m); 13C NMR (75 MHz, CDCl3Ô) 166.2, 166.1,
145.3,140.9,128.0,127.6,127.0,126.7,126.2,108.3, 95.0, 63.5, 49.0, 31.9,
29.9, 29.7, 29.6, 29.4, 29.3, 28.8, 26.4, 26.3, 14.4. FAB HRMS (acetone/
NBA) calcd for C72H101O6 1061.7598 (MþH). Found 1061.7598.
(38,10). Rf¼0.49 (CHCl3); colorless amorphous; IR (CHCl3)
n 1686
(C]O), 1647 (C]C); 1H NMR (300 MHz, CDCl3Ô) 7.45–7.11 (20H,
m), 4.18–4.13 (2H, m), 3.91–3.88 (2H, m), 3.66 (2H, m), 2.20
(6H, s), 1.55–0.78 (32H, m); 13C NMR (75 MHz, CDCl3Ô) 166.4,
166.1, 145.3, 140.9, 128.0, 127.6, 127.0, 126.7, 126.2, 108.2, 95.0,
63.2, 49.0, 31.9, 30.1, 29.7, 29.4, 28.9, 26.6, 26.3, 14.4. FAB HRMS
(acetone/NBA) calcd for C54H65O6 809.4781 (MþH). Found
809.4784.
4.3.21. 27,52-Dimethyl-3,24,28,51-tetraoxa-2,25-dioxo-29,29,50,50-
tetraphenyltricyclo[47.3.0.026,30]dopentaconta-26,52-diene
(318,20). Rf¼0.49 (CHCl3:hexane¼8:2 v/v); colorless amorphous; IR
(CHCl3) n
1686 (C]O),1647 (C]C); 1H NMR (300 MHz, CDCl3Ô) 7.55–
7.17 (20H, m), 4.23–4.15 (2H, m), 4.04–3.98 (2H, m), 3.76 (2H, m), 2.28
(6H, s), 1.66–0.93 (72H, m); 13C NMR (75 MHz, CDCl3Ô) 166.2, 166.0,
145.3,140.9,128.0,127.6,127.0,126.8,126.2,108.3, 95.0, 63.5, 49.0, 31.9,
29.83, 29.79, 29.7, 29.6, 29.4, 29.3, 28.8, 26.4, 26.3, 14.4. FAB HRMS
(acetone/NBA) calcd for C74H104O6 1088.7833 (Mþ). Found 1088.7826.
4.3.15. 19,34-Dimethyl-3,16,20,33-tetraoxa-2,17-dioxo-21,21,32,32-
tetraphenyltricyclo[29.3.0.018,22]-tetratriaconta-18,34-diene
(38,12). Rf¼0.70 (CHCl3); colorless amorphous; IR (CHCl3)
n 1686
(C]O), 1647 (C]C); 1H NMR (300 MHz, CDCl3Ô) 7.53–7.16 (20H,
m), 4.20–4.16 (2H, m), 4.03–3.93 (2H, m), 3.74–3.71 (2H, m), 2.24
(6H, s), 1.61–0.75 (36H, m); 13C NMR (75 MHz, CDCl3Ô) 166.4, 166.1,
145.3, 140.9, 128.0, 127.6, 127.0, 126.8, 126.0, 108.2, 95.0, 63.3, 49.1,
31.9, 29.9, 29.5, 29.4, 28.8, 26.6, 26.3, 14.4. FAB HRMS (acetone/NBA)
calcd for C56H68O6 836.5016 (Mþ). Found 836.5013.
4.3.22. 13,48-Dimethyl-3,10,14,47-tetraoxa-2,11-dioxo-15,15,46,46-
tetraphenyltricyclo[43.3.0.012,16]-octatetraconta-12,48-diene
(328,6). Rf¼0.63 (CHCl3); colorless amorphous; IR (CHCl3)
n 1684
(C]O), 1647 (C]C); 1H NMR (300 MHz, CDCl3Ô) 7.56–7.21 (20H,
m), 4.14–4.07 (4H, m), 3.78 (2H, m), 2.28 (6H, m), 1.67–0.95 (64H,
m); 13C NMR (75 MHz, CDCl3Ô) 165.9, 165.9, 145.4, 140.9, 128.1,
127.6, 127.0, 126.8, 126.2, 108.4, 95.1, 63.4, 49.1, 31.7, 29.7, 29.4, 29.0,
28.7, 26.2, 25.8, 14.7. FAB HRMS (acetone/NBA) calcd for C70H96O6
1032.7207 (Mþ). Found 1032.7115.
4.3.16. 27,42-Dimethyl-3,24,28,41-tetraoxa-2,25-dioxo-29,29,40,40-
tetraphenyltricyclo[37.3.0.026,30]dotetraconta-26,42-diene
(38,20). Rf¼0.56 (CHCl3); colorless amorphous; IR (CHCl3)
n 1686
(C]O), 1647 (C]C); 1H NMR (300 MHz, CDCl3Ô) 7.46–7.10 (20H,
m), 4.04–3.98 (4H, m), 3.67–3.66 (2H, t, J¼5.4 Hz), 2.20 (6H, m),
1.58–0.70 (52H, m); 13C NMR (75 MHz, CDCl3Ô) 165.98, 165.95,
145.4, 140.9, 128.0, 127.6, 126.99, 126.8, 126.2, 108.4, 95.0, 63.5,
49.1, 31.7, 29.7, 29.1, 29.04, 28.99, 28.9, 28.6, 26.2, 26.0, 14.5. FAB
HRMS (acetone/NBA) calcd for C64H84O6 948.6268 (Mþ). Found
948.6271.
4.3.23. 33,68-Dimethyl-3,30,34,67-tetraoxa-2,31-dioxo-35,35,66,66-
tetraphenyltricyclo[63.3.0.032,36]octahexaconta-32,68-diene
(328,26). Rf¼0.74 (CHCl3); colorless amorphous; IR (CHCl3)
n 1684
(C]O), 1647 (C]C); 1H NMR (300 MHz, CDCl3Ô) 7.55–7.20 (20H,
m), 4.14 (2H, m), 4.04–4.02 (2H, m), 3.76 (2H, m), 2.28 (6H, s), 1.66–
0.93 (104H, m); 13C NMR (75 MHz, CDCl3Ô) 166.1, 166.1, 145.4,
140.9, 128.0, 127.6, 127.0, 126.8, 126.2, 108.4, 95.0, 63.6, 49.0, 31.8,
29.8, 29.7, 29.6, 29.3, 28.8, 26.3, 26.2,14.5. FAB HRMS (acetone/NBA)
calcd for C90H136O6 1313.0337 (Mþ). Found 1313.0259.
4.3.17. 13,36-Dimethyl-3,10,14,35-tetraoxa-2,11-dioxo-15,15,34,34-
tetraphenyltricyclo[31.3.0.012,16]-hexatriaconta-12,36-diene
(316,6). Rf¼0.70 (CHCl3); colorless amorphous; IR (CHCl3)
n 1686
(C]O), 1647 (C]C); 1H NMR (300 MHz, CDCl3Ô) 7.55–7.19 (20H,
m), 4.15–4.04 (4H, m), 3.78 (2H, t, J¼5.9 Hz), 2.28 (6H, s), 1.68–0.96
(40H, m); 13C NMR (75 MHz, CDCl3Ô) 166.0, 166.0, 145.3, 141.0,
128.1, 127.7, 127.0, 126.7, 126.3, 108.5, 95.2, 63.4, 48.7, 31.8, 29.3,
4.3.24. 12,20-Dimethyl-3,6,9,13,19-pentaoxa-2,10-dioxo-14,14,18,18-
tetraphenyltricyclo[15.3.0.011,15]icosa-11,20-diene (51,2). Diastereomer
ratio, 50:50. Colorless microcrystals (from CH2Cl2/hexane); mp

2690
Y. Ito et al. / Tetrahedron 66 (2010) 2683–2694
132–135 ꢀC; IR (CHCl3)
n
1689 (C]O), 1643 (C]C); 1H NMR
14.6, 14.4. Anal. Calcd for C45H46O8: C, 75.61; H, 6.49. Found: C,
(400 MHz, CDCl3)
d
7.78–6.97 (20H, m), 4.60–3.45 (10H, m), 2.32–
167.2,
75.34; H, 6.62.
2.13 (6H, m), 1.37–0.85 (2H, m); 13C NMR (100 MHz, CDCl3)
d
166.5,166.0,165.2,145.0,144.8,140.6,128.1,127.9,127.7,127.4,127.0,
126.4, 126.3, 125.9, 111.2, 110.3, 96.1, 95.4, 69.9, 69.6, 64.4, 64.3, 45.7,
44.1, 36.4, 14.6, 14.4. FAB HRMS (acetone/NBA/NaI) calcd for
C41H38O7Na 665.2515 (MþþNa). Found 665.2566.
4.3.30. 15,26-Dimethyl-3,6,9,12,16,25-hexaoxa-2,13-dioxo-
17,17,24,24-tetraphenyltricyclo[21.3.0.014,18]hexacosa-14,26-diene
(54,3). Colorless microcrystals (from CH2Cl2/hexane); mp
155–157 ꢀC; IR (CHCl3)
(400 MHz, CDCl3)
4.02 (2H, m), 3.76–3.56 (10H, m), 2.25 (6H, m), 1.20–1.00 (6H, m),
0.70–0.50 (4H, m); 13C NMR (100 MHz, CDCl3)
166.9, 166.8, 165.8,
n
1692 (C]O), 1646 (C]C); 1H NMR
d
7.52–7.13 (20H, m), 4.49–4.33 (2H, m), 4.14–
4.3.25. 12,21-Dimethyl-3,6,9,13,20-pentaoxa-2,10-dioxo-14,14,19,19-
tetraphenyltricyclo[16. 3. 0. 011,15 ]henicosa-11, 21-diene
(52,2). Diastereomer ratio, 48:52. Colorless microcrystals (from
d
165.7, 145.3, 140.7, 140.6, 128.0, 127.7, 127.6, 127.0, 126.5, 126.1,
108.12, 108.06, 95.1, 70.6, 70.3, 69.7, 69.5, 62.7, 62.2, 49.0, 48.8, 31.6,
31.4, 26.7, 26.4,14.5,14.4. Anal. Calcd for C46H48O8: C, 75.80; H, 6.64.
Found: C, 75.57; H, 6.71.
CH2Cl2/hexane); mp 163–165 ꢀC; IR (CHCl3)
(C]C); 1H NMR (400 MHz, CDCl3)
(4H, m), 3.76–3.32 (6H, m), 2.20–2.00 (6H, m), 1.34–0.88 (6H, m);
13C NMR (100 MHz, CDCl3)
166.5, 166.4, 165.7, 165.5, 145.1, 144.9,
n
1691 (C]O), 1642
d
7.55–6.90 (20H, m), 4.40–4.00
d
140.9, 140.8, 128.0, 127.63, 127.6, 127.5, 126.9, 126.74, 126.5, 126.0,
125.8, 107.2, 107.0, 94.9, 94.8, 69.3, 69.2, 62.5, 61.9, 49.4, 49.3, 28.7,
27.9, 14.43, 14.39. FABMS m/z (rel intensity) 657 (32, MþH). Anal.
Calcd for C42H40O7: C, 76.81; H, 6.14. Found: C, 76.73; H, 6.16.
4.3.31. 15,27-Dimethyl-3,6,9,12,16,26-hexaoxa-2,13-dioxo-
17,17,25,25-tetraphenyltricyclo[22.3.0.014,18]heptacosa-14,27-diene
(55,3). Colorless microcrystals (from CH2Cl2/hexane); mp 137–
139 ꢀC; IR (CHCl3)
CDCl3)
3.81–3.55 (10H, m), 2.28 (6H, m), 1.39–1.09 (6H, m), 0.78–0.59 (4H,
m); 13C NMR (75 MHz, CDCl3)
166.9, 165.8, 165.7, 145.3, 140.8, 128.0,
n
1693 (C]O), 1646 (C]C); 1H NMR (300 MHz,
d
7.56–7.11 (20H, m), 4.49–4.38 (2H, m), 4.12–4.01 (2H, m),
4.3.26. 12,22-Dimethyl-3,6,9,13,21-pentaoxa-2,10-dioxo-14,14,20,20-
t e t ra p h e nyl t r i c yc l o [ 17 . 3 . 0 . 011, 15 ] d o c o s a - 11, 2 2 - d i e n e
d
(53,2). Diastereomer
(from CH2Cl2/hexane); mp 258–260 ꢀC (lit.13b mp 258–260 ꢀC); IR
(CHCl3) 7.34–7.01 (20H,
1690 (C]O),1644 (C]C); 1H NMR (CDCl3)
m), 4.37–4.34 (2H, m), 4.01–3.91 (2H, m), 3.64–3.53 (6H, m), 2.19 (3H,
s), 2.17 (3H, s),1.20–0.67 (6H, m); 13C NMR (CDCl3)
166.0, 166.0, 164.8,
164.7, 144.4, 144.3, 139.9, 139.8, 127.0, 126.7, 126.6, 125.93, 125.88,
125.6, 125.5, 125.2, 125.1, 107.1, 106.6, 94.3, 94.2, 68.3, 68.2, 61.6, 61.5,
48.5, 48.1, 31.1, 30.8, 23.1, 22.3,13.4,13.3. FABMS m/z (rel intensity) 671
(100, MþH). Anal. Calcd for C43H42O7: C, 76.99; H, 6.31. Found: C,
76.69; H, 6.31.
ratio,
49:51.
Colorless
microcrystals
127.7, 127.5, 127.0, 126.7, 126.2, 107.9, 95.20, 95.18, 70.4, 70.3, 69.8,
62.6, 62.5, 49.0, 48.9, 31.8, 30.2, 30.1, 26.43, 26.37, 14.4. FAB HRMS
(acetone/NBA) calcd for C47H51O8 743.3584 (MþH). Found 743.3561.
n
d
d
4.3.32. 15,28-Dimethyl-3,6,9,12,16,27-hexaoxa-2,13-dioxo-
17,17,26,26-tetraphenyltricyclo[23.3.0.014,18]octacosa-14,28-diene
(56,3). Colorless microcrystals (from CH2Cl2/hexane); mp 126–
128 ꢀC; IR (CHCl3)
CDCl3)
3.83–3.55 (10H, m), 2.28 (6H, m), 1.41–1.14 (4H, m), 0.94–0.64 (8H,
m); 13C NMR (75 MHz, CDCl3)
167.1, 166.9, 165.83, 165.79, 145.3,
n
1699 (C]O), 1648 (C]C); 1H NMR (300 MHz,
d
7.61–7.06 (20H, m), 4.51–4.38 (2H, m), 4.12–4.02 (2H, m),
d
4.3.27. 12,23-Dimethyl-3,6,9,13,22-pentaoxa-2,10-dioxo-14,14,21,21-
t e t ra p h e nyl t r i c yc l o [ 18 . 3 . 0 . 011, 15 ] t r i c o s a - 11, 2 3 - d i e n e
140.9, 128.1, 127.6, 127.0, 126.72, 126.67, 126.21, 126.17, 108.01,
107.97, 95.20, 95.18, 70.3, 69.8, 62.6, 48.8, 48.7, 31.8, 29.8, 29.7, 26.4,
26.3, 14.4. FAB HRMS (acetone/NBA) calcd for C48H52O8 756.3662
(Mþ). Found 756.3669.
(54,2). Diastereomer
(from CH2Cl2/hexane); mp 253–254 ꢀC; IR (CHCl3)
1642 (C]C); 1H NMR (400 MHz, CDCl3)
ratio,
38:62.
Colorless
microcrystals
1690 (C]O),
n
d
7.56–7.11 (20H, m), 4.56–
4.46 (2H, m), 4.11–4.02 (2H, m), 3.82–3.64 (6H, m), 2.32–2.23 (6H, m),
1.32–0.58 (6H, m); 13C NMR (100 MHz, CDCl3)
167.3, 166.0, 145.4,
4.3.33. 9,19-Dimethyl-3,6,10,14,18-pentaoxa-2,7-dioxo-11,11,17,17-
d
tetraphenyltricyclo[14.3.0.08,12]nonadeca-8,19-diene (70,1). Colorless
145.1, 140.9, 140.8, 128.1, 128.0, 127.7, 127.6, 127.0, 126.9, 126.6, 126.4,
126.3, 126.0, 108.4, 108.0, 95.4, 95.3, 69.8, 69.6, 63.0, 62.9, 48.3, 48.1,
32.0, 30.9, 26.1, 25.1,14.45,14.40. FABMS m/z (rel intensity), 685 (100,
MþH). Anal. Calcd for C44H44O7: C, 77.17; H, 6.48. Found: C, 76.98; H,
6.55.
microcrystals (from CH2Cl2/hexane); mp 122–125 ꢀC; IR (CHCl3)
n
1703 (C]O), 1652 (C]C); 1H NMR (300 MHz, CDCl3)
d 7.55–7.05
(20H, m), 4.72 (2H, d, J¼9.0 Hz), 4.13–3.90 (4H, m), 3.05–2.93 (2H,
m), 2.88–2.77 (2H, m), 2.27 (6H, s); 13C NMR (75 MHz, CDCl3)
d
167.1, 165.7, 144.6, 140.0, 128.2, 127.8, 127.1, 126.3, 126.0, 106.7,
94.5, 72.1, 60.9, 48.4, 14.2. FAB HRMS (acetone/NBA) calcd for
4.3.28. 15,24-Dimethyl-3,6,9,12,16,23-hexaoxa-2,13-dioxo-
17,17,22,22-tetraphenyltricyclo[19.3.0.014,18]tetracosa-14,24-diene
(52,3). Diastereomer ratio, 50:50. Colorless microcrystals (from
C40H37O7 629.2539 (MþH). Found 629.2495.
4.3.34. 12,22-Dimethyl-3,6,9,13,17,21-hexaoxa-2,10-dioxo-
14,14,20,20-tetraphenyltricyclo[17.3.0.011,15]docosa-11,22-diene
(70,2). Colorless microcrystals (from CH2Cl2/hexane); mp 208–
CH2Cl2/hexane); mp 169–171 ꢀC; IR (CHCl3)
(C]C); 1H NMR (400 MHz, CDCl3)
(4H, m), 3.80–3.53 (10H, m), 2.15–1.89 (6H, m), 1.22–0.90 (4H, m);
13C NMR (100 MHz, CDCl3)
167.0, 166.5, 165.5, 145.2, 144.9, 140.8,
n
1694 (C]O), 1650
d
7.50–7.08 (20H, m), 4.40–4.06
210 ꢀC; IR (CHCl3)
CDCl3) d 7.62–6.96 (20H, m), 4.48–4.25 (2H, m), 4.20–4.05 (3H, m),
n
1698 (C]O), 1636 (C]C9); 1H NMR (300 MHz,
d
140.7, 127.9, 127.6, 127.4, 127.0, 126.8, 126.3, 126.1, 125.9, 107.4, 106.7,
95.1, 70.5, 70.4, 69.3, 69.2, 62.6, 62.1, 48.7, 47.3, 29.0, 26.8, 14.6, 14.1.
Anal. Calcd for C44H44O8: C, 75.41; H, 6.33. Found: C, 75.63; H, 6.42.
3.93–3.83 (1H, m), 3.78–3.55 (4H, m), 3.45–3.30 (2H, m), 3.11–3.00
(1H, m), 2.89–2.78 (1H, m), 2.36 (3H, s), 2.32 (3H, s); 13C NMR
(75 MHz, CDCl3) d 168.8, 168.7, 165.5, 145.3, 145.1,140.5, 140.4, 128.1,
127.7, 127.53, 127.49, 127.0, 126.93, 126.86, 126.7, 126.3, 102.9, 102.7,
95.3, 94.8, 70.4, 70.1, 69.2, 68.9, 62.5, 62.0, 52.4, 51.9, 14.5,14.3. Anal.
Calcd for C42H40O8: C, 74.98; H, 5.99. Found: C, 74.69; H, 5.77.
4.3.29. 15,25-Dimethyl-3,6,9,12,16,24-hexaoxa-2,13-dioxo-
17,17,23,23-tetraphenyltricyclo[20.3.0.014,18]pentacosa-14,25-diene
(53,3). Diastereomer ratio, 44:56. Colorless microcrystals (from
CH2Cl2/hexane); mp 253–255 ꢀC; IR (CHCl3)
(C]C); 1H NMR (400 MHz, CDCl3)
(4H, m), 3.82–3.52 (10H, m), 2.30–2.16 (6H, m), 1.10–0.48 (6H, m);
13C NMR (100 MHz, CDCl3)
166.6, 166.5, 165.5, 145.3, 145.2, 140.7,
140.6, 128.0, 127.6, 126.8, 126.7, 126.6, 126.2, 126.1, 108.05, 95.2,
95.1, 70.8, 70.6, 69.5, 69.4, 62.7, 62.1, 48.5, 48.0, 31.6, 31.1, 23.0,
n
1698 (C]O), 1657
4.3.35. 15,25-Dimethyl-3,6,9,12,16,20,24-heptaoxa-2,13-dioxo-
17,17,23,23-tetraphenyltricyclo[20.3.0.014,18]-pentacosa-14,25-diene
(70,3). Colorless microcrystals (from CH2Cl2/hexane); mp
d
7.55–7.04 (20H, m), 4.35–4.14
d
199–201 ꢀC; IR (CHCl3)
(400 MHz, CDCl3)
(10H, m), 3.26–3.17 (2H, m), 2.84–2.73 (2H, m), 2.34 (3H, s), 2.32 (3H,
n
1698 (C]O), 1648 (C]C); 1H NMR
d 7.63–6.96 (20H, m), 4.40–4.15 (4H, m), 3.94–3.54

Y. Ito et al. / Tetrahedron 66 (2010) 2683–2694
2691
s); 13C NMR (100 MHz, CDCl3)
d
168.6,168.3,165.5,165.3,145.3,145.2,
1H NMR (300 MHz, CDCl3Ô) 7.65–7.19 (20H, m), 4.39–4.33 (2H, m),
4.20–4.14 (2H, m), 4.07 (1H, m), 4.00 (1H, m), 3.73–3.62 (12H, m),
3.58–3.52 (2H, m), 3.00–2.92 (2H, m), 2.82–2.72 (2H, m), 2.61–2.56
(1H, m), 2.49–2.46 (1H, m), 2.35 (6H, s); 13C NMR (75 Hz, CDCl3Ô)
168.60, 168.57, 165.42, 165.38, 145.1, 145.0, 140.6, 140.5, 128.1, 127.7,
127.3, 127.1, 127.07, 126.55, 126.48, 102.9, 102.8, 95.0, 94.9, 70.9,
70.8, 70.7, 69.7, 69.6, 69.38, 69.3, 69.2, 63.0, 51.8, 51.6, 14.5, 14.4. FAB
HRMS (acetone/NBA) calcd for C48H53O11 805.3588 (MþH). Found
805.3583.
140.5, 140.4, 128.2, 128.0, 127.7, 127.6, 127.3, 127.23, 127.16, 127.1, 126.9,
126.4, 126.3, 103.2, 102.9, 94.9, 94.8, 70.7, 70.5, 69.4, 69.3, 62.6, 62.3,
51.8, 51.0, 14.5. Anal. Calcd for C44H44O9: C, 73.73; H, 6.19. Found: C,
73.80; H, 6.22.
4.3.36. 18,28-Dimethyl-3,6,9,12,15,19,23,27-octaoxa-2,16-dioxo-
20,20,26,26-tetraphenyltricyclo[23.3.0.017,21]octacosa-17,28-diene
(70,4). Colorless amorphous; IR (CHCl3)
1H NMR (300 MHz, CDCl3)
7.63–7.16 (20H, m), 4.60–2.87 (22H, m),
2.33 (6H, s); 13C NMR (75 MHz, CDCl3)
168.2, 165.2, 145.6, 145.9,
n 1695 (C]O), 1647 (C]C);
d
d
4.3.41. 9,25-Dimethyl-3,6,10,14,17,20,24-heptaoxa-2,7-dioxo-
11,11,23,23-tetraphenyltricyclo[20.3.0.08,12]-pentacosa-8,25-diene
(72,1). Diastereomer ratio, 42:58. Rf¼0.35 (CHCl3:MeOH¼98:2 v/v);
128.1, 127.6, 127.5, 127.3, 127.2, 127.1, 126.9, 126.8, 126.7, 126.6, 126.4,
103., 94.9, 70.7, 70.6, 69.4, 69.1, 61.7, 51.5, 14.5. FAB HRMS (acetone/
NBA) calcd for C46H49O10 761.3326 (MþH). Found 761.3328.
colorless amorphous; IR (CHCl3)
n
1697 (C]O), 1645 (C]C); 1H
NMR (300 MHz, CDCl3Ô) 7.61–7.18 (20H, m), 4.41–4.37 (2H, m),
4.31–4.27 (2H, m), 4.03–4.02 (2H, m), 3.51–3.21 (8H, m), 2.86–2.74
(4H, m), 2.35 (3H, s), 2.31 (3H, s); 13C NMR (75 Hz, CDCl3Ô) 168.7,
168.5, 165.3, 165.2, 145.0, 140.53, 140.48, 128.1, 127.8, 127.2, 127.17,
127.12, 127.06, 127.0, 126.4, 102.9, 102.8, 94.8, 94.7, 70.62, 70.58,
70.4, 69.1, 69.0, 62.0, 61.8, 51.4, 51.1, 14.8. FAB HRMS (acetone/NBA)
calcd for C44H45O9 717.3064 (MþH). Found 717.3068.
4.3.37. 9,22-Dimethyl-3,6,9,10,14,17,21-heptaoxa-2,7-dioxo-
11,11,20,20-tetraphenyltricyclo[17.3.0.08,12]docosa-8,22-diene
(71,1). Rf¼0.49 (CHCl3:MeOH¼98:2 v/v); colorless amorphous; IR
(CHCl3)
n
1705 (C]O), 1639 (C]C); 1H NMR (300 MHz, CDCl3Ô)
7.58–7.17 (20H, m), 4.41 (2H, m), 4.30 (2H, m), 3.95 (2H, br dd, J¼8.1,
2.4 Hz), 3.59 (2H, dd, J¼9.0, 2.2 Hz), 3.11 (2H, dd, J¼9.0, 8.1 Hz), 2.66
(2H, m), 2.51 (2H, m), 2.35 (6H, s); 13C NMR (75 Hz, CDCl3Ô) 169.0,
165.4,144.9,140.5,128.1,127.8, 127.15,127.1, 127.0, 126.5, 102.6, 94.9,
70.7, 70.3, 61.8, 51.5, 14.6. FAB HRMS (acetone/NBA) calcd for
C42H41O8 673.2801 (MþH). Found 673.2804.
4.3.42. 12,28-Dimethyl-3,6,9,13,17,20,23,27-octaoxa-2,10-dioxo-
14,14,26,26-tetraphenyltricyclo[23.3.0.011,15]-octacosa-11,28-diene
(72,2). Rf¼0.27 (CHCl3:MeOH¼98:2 v/v); colorless amorphous; IR
Diastereoisomer. Rf¼0.49 (CHCl3:MeOH¼98:2 v/v); colorless
(CHCl3) n
1695 (C]O), 1647 (C]C); 1H NMR (300 MHz, CDCl3Ô)
amorphous; IR (CHCl3)
n
1697 (C]O), 1643 (C]C); 1H NMR
7.60–7.17 (20H, m), 4.36–4.31 (2H, m), 4.19–4.14 (2H, m), 4.06–4.04
(2H, m), 3.74–3.71 (4H, m), 3.50–3.42 (2H, m), 3.35–3.23 (4H, m),
3.20–3.14 (2H, m), 3.00–2.88 (4H, m), 2.34 (3H, s), 2.31 (3H, s); 13C
NMR (75 Hz, CDCl3Ô) 168.2, 165.4, 145.0, 140.5, 128.1, 128.0, 127.3,
127.1, 126.4, 103.4, 94.7, 70.3, 70.1, 69.74, 69.70, 69.3, 69.2, 62.64,
62.55, 51.1, 51.0, 14.5. FAB HRMS (acetone/NBA) calcd for C46H49O10
761.3326 (MþH). Found 761.3339.
(300 MHz, CDCl3Ô) 7.62–7.17 (20H, m), 4.54 (2H, m), 4.21 (2H, m),
4.04 (2H, br dd, J¼7.8, 2.1 Hz), 3.43 (2H, dd, J¼9.0, 2.1 Hz), 3.07
(2H, dd, J¼9.0, 7.8 Hz), 2.83–2.77 (2H, m), 2.35–2.28 (2H, m), 2.31
(6H, s); 13C NMR (75 Hz, CDCl3Ô) 168.7, 165.3, 144.8, 140.4, 128.1,
127.8, 127.1, 127.0, 126.5, 102.9, 94.9, 69.4, 69.4, 61.7, 51.4, 14.6. FAB
HRMS (acetone/NBA) calcd for C42H41O8 673.2801 (MþH). Found
673.2808.
4.3.43. 15,31-Dimethyl-3,6,9,12,16,20,23,26,30-nonaoxa-2,13-dioxo-
17,17,29,29-tetraphenyltricyclo[26.3.0.014,18]-hentriaconta-14,31-di-
ene (72,3). Rf¼0.27 (CHCl3:MeOH¼98:2 v/v); colorless amorphous;
4.3.38. 12,25-Dimethyl-3,6,9,13,17,20,24-heptaoxa-2,10-dioxo-
14,14,23,23-tetraphenyltricyclo[20.3.0.011,15]-pentacosa-11,25-diene
(71,2). Diastereomer ratio, 50:50. Rf¼0.44 (CHCl3:MeOH¼98:2 v/v);
IR (CHCl3) n
1701 (C]O), 1651 (C]C); 1H NMR (300 MHz, CDCl3Ô)
colorless amorphous; IR (CHCl3)
n
1697 (C]O), 1647 (C]C); 1H
7.61–7.19 (20H, m), 4.41–4.36 (2H, m), 4.13–4.04 (4H, m), 3.74–3.67
(8H, m), 3.58–3.49 (2H, m), 3.30–3.21 (4H, m), 3.14–2.95 (4H, m),
2.81–2.73 (2H, m), 2.33 (3H, s), 2.32 (3H, s); 13C NMR (75 Hz,
CDCl3Ô) 168.4, 165.4, 145.0, 140.4, 128.1, 127.7, 127.1, 126.4, 103.1,
94.8, 70.7, 70.2, 69.9, 69.61, 69.55, 69.3, 63.0, 51.2, 14.4. FAB HRMS
(acetone/NBA) calcd for C48H53O11 805.3588 (MþH). Found
805.3615.
NMR (300 MHz, CDCl3Ô) 7.59–7.20 (20H, m), 4.44–4.30 (2H, m),
4.20–3.97 (4H, m), 3.78–3.67 (4H, m), 3.54 (1H, dd, J¼9.5, 2.9 Hz),
3.34 (1H, dd, J¼9.5, 2.9 Hz), 3.09–3.02 (2H, m), 2.65–2.52 (4H, m),
2.37 (3H, s), 2.30 (3H, s); 13C NMR (75 Hz, CDCl3Ô) 168.5, 168.4,
165.4, 145.0, 144.9, 140.5, 140.4, 128.11, 128.1, 127.8, 127.22, 127.19,
127.16, 127.10, 126.98, 126.96, 126.4, 103.6, 103.1, 94.8, 94.7, 70.3,
69.8, 69.6, 69.5, 61.9, 51.5, 50.8, 14.47, 14.46. HRMS (acetone/NBA)
calcd for C44H45O9 717.3064 (MþH). Found 717.3078.
4.3.44. 18,34-Dimethyl-3,6,9,12,15,19,23,26,29,33-decaoxa-2,16-di-
oxo-20,20,32,32-tetraphenyltricyclo-[29.3.0.017,21]tetratriaconta-
17,34-diene (72,4). Rf¼0.25 (CHCl3:MeOH¼98:2 v/v); colorless
4.3.39. 15,28-Dimethyl-3,6,9,12,16,20,23,27-octaoxa-2,13-dioxo-
17,17,26,26-tetraphenyltricyclo[23.3.0.014,18]-octacosa-14,28-diene
(71,3). Diastereomer ratio, 50:50. Rf¼0.41 (CHCl3:MeOH¼98:2 v/v);
amorphous; IR (CHCl3)
n
1695 (C]O), 1645 (C]C); 1H NMR
(300 MHz, CDCl3Ô) 7.61–7.19 (20H, m), 4.39–4.34 (2H, m), 4.15–4.05
(4H, m), 3.71–3.55 (14H, m), 3.26–3.16 (4H, m), 3.10–3.00 (4H, m),
2.74–2.65 (2H, m), 2.33 (6H, s); 13C NMR (75 Hz, CDCl3Ô) 168.6,165.4,
145.0, 140.5, 128.1, 127.7, 127.2, 127.1, 126.5, 102.9, 94.8, 70.71, 70.66,
70.62, 70.3, 70.2, 69.94, 69.87, 69.56, 69.51, 69.33, 69.30, 63.0, 51.3,
14.5. FAB HRMS (acetone/NBA) calcd for C50H57O12 849.3850 (MþH).
Found 849.3837.
colorless amorphous; IR (CHCl3)
n
1697 (C]O), 1647 (C]C); 1H
NMR (300 MHz, CDCl3Ô) 7.61–7.18 (20H, m), 4.41–4.36 (2H, m),
4.13–4.01 (4H, m), 3.77–3.61 (9H, m), 2.52 (1H, dd, J¼9.6 Hz,
3.0 Hz), 3.02–2.96 (2H, m), 2.69–2.65 (2H, m), 2.54–2.52 (2H, m),
2.36, 2.33 (6H, s); 13C NMR (75 Hz, CDCl3Ô) 168.7, 168.6, 165.44,
165.39, 144.95, 144.90, 140.5, 128.1, 127.8, 127.25, 127.22, 127.20,
127.14, 127.06, 127.0, 126.48, 126.45, 103.1, 103.0, 94.9, 94.8, 71.0,
70.9, 70.1, 69.83, 69.77, 69.5, 69.47, 63.4, 63.3, 51.5, 51.3, 14.4. FAB
HRMS (acetone/NBA) calcd for C46H49O10 761.3326 (MþH). Found
761.3352.
4.3.45. 9,28-Dimethyl-3,6,10,14,17,20,23,27-octaoxa-2,7-dioxo-
11,11,26,26-tetraphenyltricyclo[23.3.0.08,12]-octacosa-8,28-diene
(73,1). Rf¼0.22 (CHCl3:MeOH¼98:2 v/v); colorless amorphous; IR
(CHCl3) n
1701 (C]O),1647 (C]C); 1H NMR (300 MHz, CDCl3Ô) 7.59–
4.3.40. 18,31-Dimethyl-3,6,9,12,15,19,23,26,30-nonaoxa-2,16-dioxo-
20,20,29,29-tetraphenyltricyclo[26.3.0.017,21]-hentriaconta-17,31-di-
ene (71,4). Diastereomer ratio, 50:50. Rf¼0.39 (CHCl3:MeOH¼98:2
7.19 (20H, m), 4.41–4.28 (4H, m), 4.07–4.05 (2H, m), 3.57–3.44 (8H,
m), 3.39–3.19 (4H, m), 3.01–2.89 (4H, m), 2.33 (3H, s), 2.31 (3H, s); 13C
NMR (75 Hz, CDCl3Ô) 168.4, 168.2, 165.2, 145.0, 144.9, 140.5, 128.1,
127.8, 127.2, 127.1, 127.0, 126.4, 103.2, 103.1, 94.8, 70.7, 70.6, 70.5, 70.4,
v/v); colorless amorphous; IR (CHCl3)
n 1695 (C]O), 1645 (C]C);

2692
Y. Ito et al. / Tetrahedron 66 (2010) 2683–2694
70.3, 70.1, 69.4, 69.3, 61.8, 61.7, 51.2, 14.7. FAB HRMS (acetone/NBA)
colorless amorphous; IR (CHCl3) n
1701 (C]O), 1647 (C]C); 1H
calcd for C46H49O10 761.3326 (MþH). Found 761.3344.
NMR (300 MHz, CDCl3Ô) 7.61–7.16 (20H, m), 4.34–4.32 (2H, m),
4.30–4.14 (2H, m) 4.06 (2H, m), 3.72–3.47 (18H, m), 3.34–3.30 (4H,
m), 3.12 (2H, t, J¼8.4 Hz), 3.03–2.98 (2H, m), 2.84–2.79 (2H, m), 2.33
(6H, s); 13C NMR (75 Hz, CDCl3Ô) 168.1, 165.2, 144.8, 140.4, 128.0,
127.6, 127.1, 127.03, 126.92, 126.3, 103.0, 94.6, 70.6, 70.53, 70.51,
70.2, 69.9, 69.4, 69.2, 62.6, 51.2, 14.4. FAB HRMS (acetone/NBA)
calcd for C52H61O13 893.4112 (MþH). Found 893.4118.
4.3.46. 12,31-Dimethyl-3,6,9,13,17,20,23,26,30-nonaoxa-2,10-dioxo-
14,14,29,29-tetraphenyltricyclo-[26.3.0.011,15]hentriaconta-11,31-di-
ene (73,2). Diastereomer ratio, 49:51. Rf¼0.30 (CHCl3:MeOH¼98:2
v/v); colorless amorphous; IR (CHCl3)
n 1699 (C]O), 1647 (C]C);
1H NMR (300 MHz, CDCl3Ô) 7.60–7.16 (20H, m), 4.37–4.28 (2H, m),
4.20–4.16 (2H, m) 4.06 (2H, m), 3.74–3.68 (4H, m), 3.54–3.46 (6H,
m), 3.41–3.29 (4H, m), 3.18–3.10 (2H, dd, J¼15.6, 7.5 Hz), 2.97–2.85
(4H, m), 2.33 (3H, s), 2.32 (3H, s); 13C NMR (75 Hz, CDCl3Ô) 168.2,
168.1, 165.4, 144.9, 140.5, 128.1, 127.8, 127.3, 127.11, 127.07, 126.4,
103.42, 103.35, 94.7, 70.6, 70.4, 70.3, 70.21, 70.16, 69.64, 69.56, 69.2,
62.74, 61.65, 51.1, 14.6, 14.5. FAB HRMS (acetone/NBA) calcd for
C48H53O11 805.3588 (MþH). Found 805.3597.
4.3.52. 18,40-Dimethyl-3,6,9,12,15,19,23,26,29,32,35,39-dodecaoxa-
2,16-dioxo-20,20,38,38-tetraphenyltricyclo-[35.3.0.017,21]tetraconta-
17,40-diene (74,4). Rf¼0.09 (CHCl3:MeOH¼95:5 v/v); colorless
amorphous; IR (CHCl3)
n
1695 (C]O), 1647 (C]C); 1H NMR
(300 MHz, CDCl3Ô) 7.62–7.17 (20H, m), 4.36–4.20 (2H, m), 4.19–4.13
(2H, m) 4.06 (2H, m), 3.72–3.49 (22H, m), 3.33–3.30 (4H, m), 3.12–
2.99 (4H, m), 2.81–2.76 (2H, m), 2.27 (6H, s); 13C NMR (75 Hz,
CDCl3Ô) 168.3,165.4,145.0,140.5,128.1,127.8,127.2,126.5,103.1, 94.8,
70.6, 70.2, 69.9, 69.5, 69.3, 62.8, 51.3, 14.6. FAB HRMS (acetone/NBA)
calcd for C54H65O14 937.4374 (MþH). Found 937.4384.
4.3.47. 15,34-Dimethyl-3,6,9,12,16,20,23,26,29,33-decaoxa-2,13-di-
oxo-17,17,32,32-tetraphenyltricyclo-[29.3.0.014,18]tetratriaconta-
14,34-diene (73,3). Rf¼0.30 (CHCl3:MeOH¼98:2 v/v); colorless
amorphous; IR (CHCl3)
n
1695 (C]O), 1647 (C]C); 1H NMR
(300 MHz, CDCl3Ô) 7.61–7.19 (20H, m), 4.35–4.30 (2H, m), 4.17–
4.10 (2H, m), 4.06–4.04 (2H, m), 3.73–2.78 (24H, m), 2.33 (6H, s);
13C NMR (75 Hz, CDCl3Ô) 168.4, 165.4, 144.9, 140.5, 128.1, 127.8,
127.2, 127.1, 127.1, 126.5, 103.1, 94.8, 70.7, 70.6, 70.26, 70.23, 70.0,
69.5, 69.3, 62.9, 51.2, 14.5. FAB HRMS (acetone/NBA) calcd for
C50H57O12 849.3850 (MþH). Found 849.3851.
4.4. Reaction of diene 18 with bis(3-oxobutanoate) 26 in the
presence of manganese(III) acetate
A mixture of the diene 18 (0.2 mmol) and the bis(3-oxobutanoate)
26 (0.4 mmol) was allowed to react with manganese(III) acetate
(0.4 mmol) in acetic acid (50 mL) at 100 ꢀC under an argon atmo-
sphere for 5 min. After the usual work-up, the macrodiolide 38,6
(14%), the dihydrofuran 8 (28%), and the unchanged diene 18 (26%)
were isolated.
4.3.48. 18,37-Dimethyl-3,6,9,12,15,19,23,26,29,32,36-undecaoxa-
2,16-dioxo-20,20,35,35-tetraphenyltricyclo-[32.3.0.017,21]hepta-
triaconta-17,37-diene (73,4). Rf¼0.18 (CHCl3:MeOH¼95:5 v/v);
colorless amorphous; IR (CHCl3)
n
1693 (C]O), 1645 (C]C); 1H
4.4.1. 7-Oxa-8,10-dioxoundecyl
cenyl)-5,5-diphenyl-4,5-dihydrofuran-3-carboxylate (8). Rf¼0.36
(Et2O:hexane¼5:5); colorless liquid; IR (CHCl3) 1735, 1717, 1686
(C]O); 1H NMR (300 MHz, CDCl3)
7.54–7.15 (20H, m), 6.06 (1H, t,
J¼7.5 Hz), 4.15–4.06 (4H, m), 3.75 (1H, m), 3.43 (2H, s), 2.27, 2.25
(6H, s), 2.10–0.81 (24H, m); 13C NMR (75 MHz, CDCl3)
200.6,
2-methyl-4-(10,10-diphenyl-9-de-
NMR (300 MHz, CDCl3Ô) 7.61–7.18 (20H, m), 4.36–4.31 (2H, m),
4.18–4.05 (4H, m), 3.72–3.51 (18H, m), 3.31–3.23 (4H, m), 3.11–3.03
(4H, m), 2.78–2.74 (2H, m), 2.33 (6H, s); 13C NMR (75 Hz, CDCl3Ô)
168.5, 165.4, 144.9, 140.5, 128.1, 127.8, 127.23, 127.21, 127.1, 126.5,
103.0, 94.8, 70.7, 70.62, 70.61, 70.56, 70.54, 70.19, 70.16, 69.85,
69.83, 69.54, 69.51, 69.3, 62.9, 51.3, 14.5. FAB HRMS (acetone/NBA)
calcd for C52H61O13 893.4112 (MþH). Found 893.4117.
n
d
d
167.2,165.93,165.86,145.4,142.9,141.3,140.9,140.29,130.3,129.9,
128.1, 127.7, 127.2, 127.1, 126.8, 126.7, 126.2, 108.4, 108.3, 95.0, 65.3,
63.4, 50.1, 49.1, 31.8, 31.6, 29.9, 29.8, 29.7, 29.25, 29.18, 29.1, 28.6,
28.4, 26.25, 26.15, 25.8, 25.7, 25.5, 30.2, 14.7. FAB HRMS (acetone/
NBA/NaI) calcd for C50H58O6Na 777.4131 (MþþNa). Found
777.4196.
4.3.49. 9,31-Dimethyl-3,6,10,14,17,20,23,26,30-nonaoxa-2,7-dioxo-
11,11,29,29-tetraphenyltricyclo[26.3.0.08,12]-hentriaconta-8,31-diene
(74,1). Diastereomer ratio, 49:51. Rf¼0.11 (CHCl3:MeOH¼98:2 v/v);
colorless amorphous; IR (CHCl3) n
1701 (C]O), 1647 (C]C); 1H NMR
(300 MHz, CDCl3Ô) 7.58–7.19 (20H, m), 4.42–4.27 (4H, m), 4.04
(2H, m), 3.65–3.46 (10H, m), 3.38–3.30 (4H, m), 3.21–3.13 (2H, m),
3.00–2.87 (4H, m), 2.311(3H, s), 2.308 (3H, s); 13C NMR (75 Hz, CDCl3Ô)
168.34, 168.26, 165.11, 165.09, 144.94, 144.92, 140.5, 128.1, 127.8, 127.3,
127.12, 127.06, 126.4, 103.14, 103.10, 94.8, 70.72, 70.69, 70.41, 70.39,
70.2, 69.5, 62.60, 61.56, 51.22, 51.17, 14.74, 14.72. FAB HRMS (acetone/
NBA) calcd for C48H53O11 805.3588 (MþH). Found 805.3588.
4.5. Alternative synthesis of dihydrofurancarboxylate 8
3,4-Dihydro-2H-pyran (0.4205 g, 5 mmol) was dropwise added to
a mixture of hexanediol (0.591 g, 5 mmol) and a catalytic amount of
p-toluenesulfonic acid in dry THF (20 mL), and the reaction mixture
was stirred overnight. The reactionwas quenched with water and the
aqueous solution was extracted with CHCl3. The extract was washed
with brine (20 mL) and a saturated aqueous solution of Na2CO3
(20 mL), dried over anhydrous MgSO4, and concentrated to dryness.
The residue was separated by silica gel column chromatography
eluting with Et2O/hexane (8:2), giving 6-(2-tetrahydropyranyl)ox-
yhexan-1-ol (0.474 g, 47%) as a colorless oil. To a solution of
6-(2-tetrahydropyranyl)oxyhexan-1-ol (1.672 g, 8.2 mmol) and
imidazole (1.28 g, 18.8 mmol) in dry THF (30 mL), diketene (1.46 mL,
18.8 mmol) was then added dropwise at 0 ꢀC. After the addition, the
reaction mixture was stirred for 2 h at room temperature. The re-
action was quenched with water and the aqueous mixture was
extracted with CHCl3. The extract was washed with brine (20 mL) and
a saturated aqueous solution of Na2CO3 (20 mL), dried over anhy-
drous MgSO4, and concentrated to dryness. The crude products were
separated by silica gel column chromatography eluting with CHCl3,
affording the THP-protected hexamethyl 3-oxobutanoate 9 (1.472 g,
62%) as a colorless oil.
4.3.50. 12,34-Dimethyl-3,6,9,13,17,20,23,26,29,33-decaoxa-2,10-di-
oxo-14,14,32,32-tetraphenyltricyclo-[29.3.0.011,15]tetratriaconta-
11,34-diene (74,2). Rf¼0.11 (CHCl3:MeOH¼98:2 v/v); colorless
amorphous; IR (CHCl3)
n
1699 (C]O), 1651 (C]C); 1H NMR
(300 MHz, CDCl3Ô) 7.61–7.18 (20H, m), 4.35–4.29 (2H, m), 4.21–4.16
(2H, m) 4.06 (2H, m), 3.74–3.48 (14H, m), 3.35–3.31 (4H, m), 3.17–3.10
(2H, m), 2.98–2.93 (2H, m), 2.87–2.82 (2H, m), 2.322 (3H, s), 2.318
(3H, s); 13C NMR (75 Hz, CDCl3Ô) 168.04, 168.0, 165.2, 144.8, 140.4,
128.0, 127.7, 127.2, 127.1, 127.0, 126.4, 103.2, 103.1, 94.7, 70.69, 70.67,
70.62, 70.3 70.1, 70.0, 69.54, 69.50, 69.2, 62.6, 51.1, 14.5. FAB HRMS
(acetone/NBA) calcd for C50H57O12 849.3850 (MþH). Found 849.3847.
4.3.51. 15,37-Dimethyl-3,6,9,12,16,20,23,26,29,32,36-undecaoxa-
2,13-dioxo-17,17,35,35-tetraphenyltricyclo-[32.3.0.014,18]hepta-
triaconta-14,37-diene (74,3). Rf¼0.17 (CHCl3:MeOH¼95:5 v/v);

Y. Ito et al. / Tetrahedron 66 (2010) 2683–2694
2693
A mixture of the diene 18 (0.2 mmol) and the butanoate 9
(0.13 mmol) was allowed to react with manganese(III) acetate
(0.6 mmol) in acetic acid (50 mL) at 100 ꢀC under an argon atmo-
sphere for 15 min. After the usual work-up, the dihydrofuran 10
(59%) was obtained. The dihydrofuran 10 was treated with diketene
in dry THF at room temperature for 24 h in the presence of imidazole
to give the corresponding dihydrofurancarboxylate 8 in 66% yield.
4.5.1. 6-Hydroxyhexyl 2-methyl-4-(10,10-diphenyl-9-decyl)-5,5-di-
phenyl-4,5-dihydrofuran (10). Rf¼0.44 (CHCl3); colorless liquid; IR
(CHCl3)
n
1724 (C]O), 1686 (C]C); 1H NMR (300 MHz, CDCl3)
d
7.54–7.14 (20H, m), 6.06 (1H, t, J¼7.5 Hz), 4.14–4.06 (2H, m), 3.76
(1H, t, J¼7.5 Hz), 3.61 (2H, t, J¼6.3 Hz), 2.27 (3H, s), 2.10–2.03
(2H, m), 1.68–0.90 (22H, m); 13C NMR (75 MHz, CDCl3)
200.6,
d
167.2, 166.0, 165.7, 145.4, 142.7, 141.3, 140.9, 140.3, 130.3, 130.0,
128.0, 127.6, 127.2, 127.0, 126.8, 126.2, 108.3, 95.0, 63.4, 62.8, 32.6,
31.6, 29.9, 29.8, 29.7, 29.25, 29.18, 29.1, 28.7, 26.2, 25.9, 25.4, 14.7.
FAB HRMS (acetone/NBA/NaI) calcd for C46H54O4Na 693.3920
(MþþNa). Found 693.3953.
O
O
O
O
O
O
H
H
Me
Me
4.6. Manganese(III)-based intramolecular cyclization of
dihydrofurancarboxylate 8
O
O
Ph
Ph
Ph
Ph
The dihydrofurancarboxylate 8 (0.2 mmol) was oxidized with
manganese(III) acetate (0.44 mmol) in acetic acid (100 mL) at
100 ꢀC for 7 min under an argon atmosphere. After the usual work-
up, the macrodiolide 38,6 was isolated in 78% yield.
Figure 2. ORTEP drawing of meso-macrodiolide 53,3
.
4.7. X-ray analysis of macrodiolides 54,2, 53,3, and 70,3
All measurements were made using an imaging plate diffrac-
tometer with graphite monochromated Mo
Ka
radiation
(l¼0.71069 Å). The data reductions were carried out by the PROCESS-
AUTO program package, and Lorentz and polarization corrections
were performed. Corrections for the secondary extinctions were
applied. The structures were solved by the direct method and were
refined on SIR-92.18 The refinements were done by the least-squares
full matrix method, with anisotropic displacement parameters for all
non-hydrogen atoms. The hydrogen atoms were included but not
refined. All calculations were performed using the teXsan19 crystal-
lographic software package of Molecular Structure Corporation. The
crystallographic data (excluding structure factors) for the structures
in this paper have been deposited with the Cambridge Crystallo-
graphic Data Centre as supplementary publication numbers CCDC
751794 for 54,2 (Fig. 1), 751795 for 70,3 (Fig. 3), and 751796 for 53,3
(Fig. 2). Copies of the data can be obtained, free of charge, on appli-
cation to CCDC,12 Union Road, Cambridge, CB2 1EZ, UK [fax: þ44(0)-
1223-336033 or e-mail: deposit@ccdc.cam.ac.uk.
O
O
O
O
O
O
H
H
Me
O
Me
O
O
Ph
Ph
Ph
Ph
Acknowledgements
Figure 3. ORTEP drawing of DL-macrodiolide 70,3
.
This research was supported by Grants-in-Aid for Scientific
Research (C), No.15550039 and No.19550046, from the Japan Society
for the Promotion of Science. We gratefully acknowledge Professor
Teruo Shinmyozu, Institute for Materials Chemistry and Engineering,
Kyushu University, Japan, and Dr. Mikio Yasutake, Graduate School of
Science and Engineering, Saitama University, Japan, for the
measurement of the high-resolution FAB mass spectrum and X-ray
analysis.
with this article can be found in the online version, at doi:10.1016/
j.tet.2010.02.022.
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