Manganese(III)-based dioxapropellane synthesis using tricarbonyl compounds

Article abstract of DOI:10.1016/j.tet.2007.12.017

The manganese(III)-induced oxidative cyclization of 3-(2-oxoethyl)piperidine-2,4-diones was conducted in the presence of 1,1-diarylethenes at reflux temperature to produce 3-aza-7,12-dioxatricyclo[4.3.3.0^1,6]dodec-8-en-2-ones, simply called azadioxa[4.3.3]propellanes, in excellent yields. A similar oxidation of 2-(2-oxoethyl)cycloalkane-1,3-diones gave the corresponding [4.3.3]-, [5.3.3]-, and [6.3.3]-propellanes. The oxidation of 3-oxopropyl-substituted cycloalkane-1,3-diones also afforded the corresponding propellanes along with the 3-oxopropyl-substituted bicyclic intermediates. The bicyclic intermediates were definitely converted into the corresponding propellanes in the presence of a Lewis acid. The structure determination and the reaction pathway were also described.

Full text of DOI:10.1016/j.tet.2007.12.017

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 1620e1634
www.elsevier.com/locate/tet
Manganese(III)-based dioxapropellane synthesis using
tricarbonyl compounds
Kentaro Asahi a, Hiroshi Nishino b,
*
a Department of Materials and Life Sciences, Graduate School of Science and Technology, Kumamoto University,
Kurokami 2-39-1, Kumamoto 860-8555, Japan
b Department of Chemistry, Graduate School of Science and Technology, Kumamoto University,
Kurokami 2-39-1, Kumamoto 860-8555, Japan
Received 12 November 2007; received in revised form 5 December 2007; accepted 8 December 2007
Available online 14 December 2007
Abstract
The manganese(III)-induced oxidative cyclization of 3-(2-oxoethyl)piperidine-2,4-diones was conducted in the presence of 1,1-diarylethenes
at reflux temperature to produce 3-aza-7,12-dioxatricyclo[4.3.3.01,6]dodec-8-en-2-ones, simply called azadioxa[4.3.3]propellanes, in excellent
yields. A similar oxidation of 2-(2-oxoethyl)cycloalkane-1,3-diones gave the corresponding [4.3.3]-, [5.3.3]-, and [6.3.3]-propellanes. The
oxidation of 3-oxopropyl-substituted cycloalkane-1,3-diones also afforded the corresponding propellanes along with the 3-oxopropyl-substituted
bicyclic intermediates. The bicyclic intermediates were definitely converted into the corresponding propellanes in the presence of a Lewis acid.
The structure determination and the reaction pathway were also described.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
In recent years, the manganese(III)-based oxidations have
been developed by us and other research groups.8 1,3-Dicar-
bonyl compounds can readily form the manganese(III)-enolate
complex in the presence of manganese(III) acetate in acetic
acid. Subsequently, the enolate complex would provide the
electron donoreacceptor-like complex with electron-rich al-
kenes followed by the one-electron oxidation to produce active
carbon radicals.9 These carbon radicals have then been used
for the carbonecarbon bond formation, the peroxidation by
trapping molecular oxygen,10 and the generation of various
important cyclic compounds in organic systhesis.8a Recently,
we reported that the reaction of 1,1-disubstituted ethenes
with 2-(2-oxoethyl)malonates in the presence of a stoichiomet-
ric amount of manganese(III) acetate in boiling acetic acid
produced 2,8-dioxabicyclo[3.3.0]oct-3-enes via the cycloaddi-
tionetandem cyclization.11 The 2,8-dioxabicyclo[3.3.0]oct-3-
ene skeleton is found in biologically and pharmacologically
active compounds, such as the insect antifeedant, clerodin, iso-
lated from Clerodendrum infortunatum.12 Therefore, the man-
ganese(III)-based tandem cyclization might be useful for the
synthesis of functionalized 2,8-dioxabicyclo[3.3.0]oct-3-enes.
Propellanes containing a tricyclic system connected by
a carbonecarbon single bond are one of the synthetic targets
in organic synthesis due to their broad spectra of biological
and pharmacological activities as well as their challenging
molecular framework.1 Some of these propellanes in nature
display antibacterial,2 antibiotic,3 anticancer,2b antifungal,4
and platelet-activating factor antagonistic activities.5 Hence,
many synthetic research groups have investigated the total
synthesis of these natural products and their derivatives.6
Some heterocycles containing the furopyridinone skeleton
also possess antifungal and antibacterial effects.7 For example,
cladobotryal and its isomer derived from the metabolites of the
fungus Cladobotryum varium have an inhibitory effect on the
growth of plant pathogens and moderate activity against some
drug-resistant bacteria.7a
* 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 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.12.017

K. Asahi, H. Nishino / Tetrahedron 64 (2008) 1620e1634
1621
Table 1
Oxidation of a mixture of 1,1-diarylethenes 1 and 3-(2-oxoethyl)piperidine-
As a continuation of our study, we have advanced the manga-
nese(III)-induced oxidation using 3-(2-oxoethyl)piperidine-
2,4-diones in the hope of constructing novel and unique
azadioxapropellanes, which possess both the furopyridinone
and 2,8-dioxabicyclo[3.3.0]oct-3-ene frameworks.13 In this
paper, we report the successful synthesis of 3-aza-7,12-dioxa-
tricyclo[4.3.3.01,6]dodec-8-en-2-ones, the so-called azadi-
oxa[4.3.3]propellanes, and their analogs derived from various
oxoalkyl-substituted cyclic 1,3-dicarbonyl compounds using
simple alkenes.
2,4-diones 2 with manganese(III) acetatea
b
Entry
1
2
1/2/Mn(OAc)3
Time (min)
Product (yield,c %)
1
1a
1b
1c
1a
1d
1e
1a
1a
1a
1a
1a
1a
1a
1a
1a
1f
2a
2a
2a
2a
2a
2a
2b
2c
2d
2e
2f
1:1.2:3
1:1.3:3.5
1:1.3:3
1:1.2:3
1:1.6:4
1:1.5:3
1:1.5:3
1:1.5:3
1:1.5:3
1:1.5:3
1:1.5:3
1:1.5:3
1:1.5:3
1:1.2:3
1:1.5:3
1:1.5:4
1
1.5
1
3aa (53)
3ba (90)
3ca (94)
3aa (87)
3da (73)
3ea (62)
3ab (80)
3ac (93)
3ad (87)
3ae (78)
3af (93)
3ag (86)
3ah (90)
3aa (98)
3ah (93)
3fi (88)
4aa (9)
4ba (4)
2
3
4
10
10
10
10
10
10
10
10
10
10
10
10
10
4aa (9)
4da (10)
4ea (4)
4ab (4)
4ac (6)
4ad (6)
4ae (11)
4af (4)
4ag (4)
4ah (4)
5
6
7
8
9
10
11
12
13
14d
15d
16d
a
2. Results and discussion
2g
2h
2a
2h
2i
2.1. Manganese(III)-based oxidation of a mixture of various
alkenes 1aef and 3-(2-oxoethyl)piperidine-2,4-diones 2aei
We initially attempted the oxidation of a mixture of 1,1-
diphenylethene(1a) (0.5 mmol) and 1-benzyl-3-(2-oxo-2-phenyl-
ethyl)piperidine-2,4-dione (2a) (0.6 mmol) with manganese(III)
acetate dihydrate (1.5 mmol) in glacial acetic acid (20 mL) at re-
flux temperature. The alkene 1a was consumed within 1 min and
four productswere isolatedafter theirchromatographic separation
(Scheme 1 and Table 1, entry 1). The four products were deter-
mined by spectroscopic methods to be azadioxa[4.3.3]propellane
3aa (53%) as the major product along with a small amount of
by-products, azatrioxa[4.4.3]propellane 4aa (9%), and an insep-
arable mixture of acetates 5aa (13%) and 6aa (13%) (vide infra).
The reaction of the alkene 1 (0.5 mmol) with 3-(2-oxoethyl)piperidine-
diones 2 was carried out in glacial acetic acid (20 mL) in the presence of
manganese(III) acetate dihydrate in air at reflux temperature.
b
Molar ratio.
Isolated yield based on the amount of the alkene 1 used.
c
d
Before the oxidation, the mixture was degassed under reduced pressure for
30 min using an ultrasonicator followed by argon displacement, and freshly
prepared manganese(III) acetate was used in the reaction.
A similar reaction of other alkenes 1bee with 2aeh also gave
similar results except for the reaction of 1c with 2a (Table 1, en-
try 3) (see Supplementary data). Since the azadioxapropellane
3aa and the acetates 5 and 6 must be formed from the same in-
termediate, a mixture of acetates 5 and 6 was heated under
reflux in acetic acid for 10 min. As a result, the acetates 5 and
6 were converted into the corresponding propellane 3aa in
a 92% isolated yield. Therefore, the continuous heating for
10 min after finishing the oxidation resulted in the exclusivepro-
duction of the azadioxapropellanes 3 (Table 1, entries 4e13).
In our previous study, we reported the synthesis of azadioxa-
bicyclo[4.4.0]decanones using the manganese(III)-catalyzed
aerobic oxidation of 2,4-piperidinediones at ambient tempera-
ture.8b The endoperoxide ring was derived from the molecular
oxygen dissolved in the solvent.10 In fact, when the reaction
was carried out using a sufficient amount of manganese(III)
acetate at elevated temperature under argon, the azadioxabicy-
clodecanones were not produced, while only the azaoxabicy-
clo[4.3.0]nonanones were obtained.8b Therefore, in order to
avoid the formation of the minor product 4, the complete de-
gassing under reduced pressure for 30 min using an ultrasoni-
cator followed by argon displacement before the oxidation and
also the use of freshly prepared manganese(III) acetate could
control the formation of 4, and the sole production of the
azadioxapropellanes 3 was achieved (Table 1, entries 14e16).
O
R2
R3
R1
Mn(OAc)3
+
N
AcOH, reflux
R1
O
O
1a-f
2a-i
R3
R3
O
O
6
2
7
:
1a
1b
1c
1d
1e
1f
N
N
R
1 = Ph
1
10
R1 = 4-Me-C6H4
R1
:
:
:
:
:
4
4
R1
R1
1
R2
R1
R2
R1 = 4-MeO-C6H4
R1 = 4-Cl-C6H4
R1 = 4-F-C6H4
R1 = 2-naphthyl
8
O
6
O
O
O
O
3
4
R
R
R
R
R
R
R
R
R
2 = Ph, R3 = Bn
3aa, 4aa
3ba, 4ba
3ca
R1 = Ph, R2 = Ph, R3 = Bn
:
:
:
:
:
:
2a
2b
2c
2d
2e
2f
:
:
:
:
:
:
:
:
:
:
:
:
:
2 = 4-Me-C6H4, R3 = Bn
2 = 4-Cl-C6H4, R3 = Bn
2 = Ph, R3 = Me
R1 = 4-Me-C6H4, R2 = Ph, R3 = Bn
1 = 4-MeO-C6H4, R2 = Ph, R3 = Bn
R1 = 4-Cl-C6H4, R2 = Ph, R3 = Bn
1 = 4-F-C6H4, R2 = Ph, R3 = Bn
R
3da, 4da
3ea, 4ea
3ab, 4ab
3ac, 4ac
3ad, 4ad
3ae, 4ae
3af, 4af
3ag, 4ag
3ah, 4ah
3fi
2 = Ph, R3 = Et
R
2 = Ph, R3 = Pr
R1 = Ph, R2 = 4-Me-C6H4, R3 = Bn
2 = Ph, R3 = i-Pr
2 = Ph, R3 = Ph
2g :
R
R
1 = Ph, R2 = 4-Cl-C6H4, R3 = Bn
1 = Ph, R2 = Ph, R3 = Me
:
2h
2 = t-Bu, R3 = t-Bu
:
2i
R1 = Ph, R2 = Ph, R3 = Et
R
1 = Ph, R2 = Ph, R3 = Pr
R1 = Ph, R2 = Ph, R3 = i-Pr
R1 = Ph, R2 = Ph, R3 = Ph
R
1 = 2-naphthyl, R2 = t-Bu, R3 = t-Bu
O
O
O
O
Ph
Ph
Bn
AcO
Ph
Bn
2.2. Structure determination
N
Ph
Ph
N
Ph
O
O
The 1H NMR spectrum of 3aa showed the two characteris-
tic pairs of an AB quartet assigned to the benzyl protons and
H-10 methylene protons at d 4.66 (1H, d, J¼14.9 Hz), 4.44
OAc
5
6
Scheme 1.

1622
K. Asahi, H. Nishino / Tetrahedron 64 (2008) 1620e1634
O
(1H, d, J¼14.9 Hz), 3.59 (1H, d, J¼13.4 Hz), and 2.97 (1H, d,
J¼13.4 Hz), respectively. One of the H-10 methylene protons
(d 2.97) might be shielded by the anisotropic effect of the al-
kenic double bond in the dihydrofuran ring. The most charac-
teristic peak of the sp2 proton (H-9) was confirmed at d 5.19
(1H, s). The methylene protons of H-4 and H-5 appeared as
a geminal and vicinal coupling pattern (ddd), respectively. In
addition, one of the H-5 protons (d 2.44) was shifted downfield
compared to the corresponding methylene protons of 1-benz-
ylpiperidine-2-one (calculated d 1.55). It was supposed that
the proton should locate the space adjacent to the dihydro-
and tetrahydrofuran rings, in other words, it was suggested
the three-dimensional structure having two fused furan rings.
In the 13C NMR spectrum, an amide carbonyl carbon appeared
at d 170.5, and two characteristic sp2 carbons were observed at
d 156.3 (C-8) and d 99.0 (C-9) due to a dihydrofuran ring. The
peaks for the two quaternary carbons at the propellane axis ap-
peared at d 115.9 and 63.8 together with the quaternary carbon
attached to the oxygen of tetrahydrofuran at d 89.8. The chem-
ical shift of these three quaternary carbons was quite similar to
that of the azatrioxapropellane, of which the structure was
characterized by X-ray crystallography.8s All the peaks in
the NMR spectrum were also correlated by HeH COSY and
HeC COSY. Furthermore, the absorption band at 1647 cmꢀ1
was assigned to the amide carbonyl in the IR spectrum. There-
fore, the structure was determined to be 3-benzyl-8,11,11-tri-
phenyl-3-aza-7,12-dioxatricyclo[4.3.3.01,6]dodec-8-en-2-one
(3aa) based on these spectral data and the result of the high res-
olution FAB mass spectrum. The spectroscopic data of the mi-
nor product 4aa were quite similar to those of the propellane
3aa except for the ketal carbon at C-1, the quaternary carbon
of the ring junction at C-6, and the quaternary carbon attached
to the oxygen at C-4, which were slightly shifted upfield (4e
9 ppm) in the 13C NMR spectrum. The conclusive difference
was the Rf value for the TLC and an extra oxygen in the FAB
mass spectra as well as the combustion analysis (see Section
4). Accordingly, the minor product 4aa was tentatively assigned
as 8-aza-2,3,11-trioxa[4.4.3]propellane. The other minor prod-
ucts 5 and 6 were chromatographically inseparable, however,
the acetate 5 could be isolated by fractional recrystallization
from ethyl acetateehexane.
R4
R1
Mn(OAc)3
+
n
AcOH, reflux
R2
1a,g-i
O
O
R3
R3
7a-e
R4
O
O
O
n R3
R3
n R3
R3
R = R2 = Ph
1
R1
R2
:
:
:
:
1a
R4
O
O
R = Ph, R2 = Me
1
R1 R2 O
1g
1h
1i
R = Ph, R2 = H
1
8
9
1
2
R = N(Bn)Boc, R = CO2Me
R = Me, R4 = Ph, n = 1
3
:
:
8aa :
7a
R
R
R
1 = R2 = Ph, R3 = Me, R4 = Ph, n = 1
1 = R2 = Ph, R3 = H, R4 = Ph, n = 1
1 = R2 = Ph, R3 = H, R4 = 2-naphthyl
7b R = H, R4 = Ph, n = 1
3
8ab
:
7c R = H, R4 = 2-naphthyl,
:
3
:
8ac
n = 1
n = 1
R = H, R4 = Ph, n = 2
3
:
7d
8ad
:
9ad
R
1 = R2 = Ph, R3 = H, R4 = Ph, n = 2
7e R = H, R4 = Ph, n = 3
3
:
8ae
:
9ae
R
1 = R2 = Ph, R3 = H, R4 = Ph, n = 3
8gb :
8hb :
8ib :
R
R
R
R
1 = Ph, R2 = Me, R3 = H, R4 = Ph, n = 1
1 = Ph, R2 = H, R3 = H, R4 = Ph, n = 1
1 = N(Bn)Boc, R2 = CO2Me, R3 = H,
4 = Ph, n = 1
O
Me
Me
O
O
Mn(OAc)3
Ph
Me
Me
+
1a
+
AcOH
reflux
Ph
Ph
Ph
Ph
Ph
Me
O
O
O
Ph
O
O
O
O
Me
7f
8af
8af'
O
O
O
O
O
Mn(OAc)3
EtO
EtO
Ph
Ph
+
1a
+
AcOH
reflux
Ph
Ph
O
O
O
O
7g
10
11
Scheme 2.
excess amount of the oxidant was employed since 1i was
only converted in 60%, the yield of 8ib did not increase (Table
2, entry 9). Dimethylcyclohexanedione 7f produced isomeric
propellanes 8af and 8af0 (Table 2, entry 10). By using cyclo-
hexanedioneacetate 7g, the propellanelactone 10 was pro-
duced along with a bicyclic compound 11 (Table 2, entry 11).
A similar reaction using the 3-oxopropyl-substituted cyclo-
alkanediones 12aee was next investigated. The cycloalkane-
diones 12aec gave the desired propellanes 13, however, the
bicyclic intermediates 14 were also isolated as a by-product
(Scheme 3 and Table 3, entries 1e3). The continuous heating
after finishing the oxidation did not effectively increase the
yield of 13. 2-(2-Oxocyclohexylmethyl)cyclohexane-1,3-
dione (12d) gave a good result, though an excess amount of
the oxidant was needed to consume 1a (Table 3, entry 4).
The reaction of cyclohexanedionepropanoate 12e failed to pro-
duce the propellanelactone, but the bicyclic compounds 14ae
and 15 were obtained (Table 3, entry 5). In this case, the con-
tinuous heating resulted in decreased yields (Table 3, entry 6).
The quinoline and coumarin derivatives are found in a wide
range of biologically active natural products.14,15 Therefore, we
next applied the propellane synthesis to the oxoalkyl-substituted
2.3. Application of the propellane formation
In order to examine the applicability of the manganese(III)-
based propellane formation, the reaction using 2-(2-oxoethyl)-
cycloalkane-1,3-diones 7aeg was carried out under similar
oxidation conditions to give the desired propellanes 8 and 10
(Scheme 2 and Table 2). The ring size of the cycloalkane-
diones 7 was bigger, the yield of the propellanes 8 was lower,
and the production of the spiroalkanes 9 was promoted (Table
2, entries 4 and 5). 2-Phenylpropene (1g) and styrene (1h)
barely afforded 8gb and 8hb, respectively, together with an
intractable mixture (Table 2, entries 6 and 7). The reaction us-
ing 2-methylpropene or 2-ethyl-1-butene became messy and
no propellanes were isolated. 2-Aminoacrylate 1i also gave
8ib as a 1:1 diastereomixture (Table 2, entry 8). Although an

K. Asahi, H. Nishino / Tetrahedron 64 (2008) 1620e1634
1623
Table 2
Oxidation of a mixture of alkenes 1 and 2-(2-oxoethyl)cycloalkane-1,3-diones
7 with manganese(III) acetatea
Table 3
Oxidation of a mixture of 1,1-diphenylethene (1a) and 2-(3-oxopropyl)-
cycloalkane-1,3-diones 12aee with manganese(III) acetatea
Entry
1
7
Molar
ratiob
Time
(min)
Product
(yield,c %)
Entry
Cycloalkane
Molar
ratiob
Time
(min)
Product (yield,c %)
1
2
3
4
1a
1a
1a
1a
7a
7b
7c
7d
n¼1
n¼1
n¼1
n¼2
1:1.5:3
1:1.5:4
1:1.5:4
1:1.2:3
10
1
8aa (80)
8ab (81)
8ac (80)
8ad (66)
9ad (19)
8ae (27)
9ae (31)
8gb (17)e
8hb (22)
8ib (50)e
8ib (44)e
8af (34)
8af0 (32)
10 (75)
1
12a
n¼0
1:1.2:3
10
13aa (21)
14aa (37)
14aa0 (34)
14ab (31)
14ac (27)
5
10
2
12b
12c
12d
12e
12e
n¼1
n¼1
n¼1
n¼1
n¼1
1:1.2:3
1:1.5:3.5
1:2:8
10
10
10
1
13ab (49)
13ac (47)
13ad (81)
14ae (79)
14ae (61)
3
4
5
1ad
7e
n¼3
1:1.2:3
2
5d
6d
a
1:1.5:4
1:1.5:4
15 (10)
15 (19)
10
6
1g
1h
1ig
1ih
1a
7b
7b
7b
7b
7f
n¼1
n¼1
n¼1
n¼1
n¼1
1:1.5:4
1:2:2.5f
1:3:6
5
The reaction of 1a (0.5 mmol) with 2-(3-oxopropyl)cycloalkanedione 12
was carried out in glacial acetic acid (20 mL) in the presence of manga-
nese(III) acetate dihydrate in air at reflux temperature.
7
5
8
1
9
10
1:3:10
1:1.7:4
1.5
5
b
Ratio of 1a/12/Mn(OAc)3.
Isolated yield based on the amount of 1a used.
c
d
Before the oxidation, the mixture was degassed under reduced pressure for
30 min using an ultrasonicator followed by argon displacement.
11
1a
7g
n¼1
1:1.5:4
0.5
11 (19)
a
The reaction of the alkene 1 (0.5 mmol) with 2-(2-oxoethyl)cycloalkane-
dione 7 was carried out in glacial acetic acid (20 mL) in the presence of
manganese(III) acetate dihydrate at reflux temperature. Before the oxidation,
the mixture was degassed under reduced pressure for 30 min using an ultraso-
nicator followed by argon displacement.
the intermediates 19 and 20aa (Scheme 4 and Table 4, entry 1).
The further heating for 30 min after finishing the oxidation of
16a did not lead to an increased yield of the propellanes, but de-
creased the product yields. Quinolinone 16b and coumarin 16c
gave the corresponding [4.4.3]propellanes 17ab and 17ac in ex-
cellent yields (Table 4, entries 2 and 4). The continuous heating
after finishing the oxidation of 16b was also not effective for
the formation of 17ab (Table 4, entry 3).
b
Ratio of 1/7/Mn(OAc)3.
Isolated yield based on the amount of the alkene 1 used.
c
d
The alkene 1a was recovered in 11%.
The product was obtained as a 1:1 diastereomixture.
e
f
Copper(II) acetate (0.75 mmol) was added as a co-oxidant.
The alkene 1i was recovered in 40%.
The alkene 1i was recovered in 24%.
g
h
2.4. Lewis acid-induced cyclization of propellane
intermediates
4-hydroxyquinolinones 16a,b and 4-hydroxycoumarin 16c in or-
dertofunctionalizetheircompounds. Thereactionof16agavean
isomeric mixture of [4.3.3]propellanes 17aa and 18together with
The propellane formation using the 3-oxopropyl-substituted
cycloalkanediones 12 deserves comment. Since the continuous
O
O
O
Ph
Ph
Mn(OAc)3
AcOH
reflux
OH
X
O
n R1
R1
Ph
Ph
+
R2
1a
O
O
n
Mn(OAc)3
Ph
Ph
Ph
n
1a
+
O
R1
O
O
n
R1
AcOH
reflux
O
X
O
12
13
16
17
R1 = H, R2 = Ph, n = 0
R1 = H, R2 = Ph, n = 1
R1 = Me, R2 = Ph, n = 1
:
12a
12b
12c
12e
:
:
17aa :
:
:
:
R2
O
EtO
O
X = N-Me, n = 0
X = N-Me, n = 1
X = O, n = 1
16a
16b
16c
X = N-Me, n = 0
X = N-Me, n = 1
X = O, n = 1
17ab :
R
1 = H, R2 = OEt, n = 1
:
O
O
:
17ac
Ph
Ph
Ph
Ph
n
R1 = H, n = 0
13aa :
13ab :
R1
O
O
O
Ph
OH
Ph
O
Ph
Ph
R
R
1 = H, n = 1
R3 R1
14
O
O
N
O
N
1 = Me, n = 1
:
13ac
Ph
n
15
Ph
O
Ph
Ph
Ph
R1 = H, R2 = Ph, R3 = OH, n = 0
N
Me
O
O
14aa :
14aa':
O
1 = H, R2 = Ph, R3 = OAc, n = 0
Me
Me
R
R1 = H, R2 = Ph, R3 = OH, n = 1
R1 = Me, R2 = Ph, R3 = OH, n = 1
R1 = H, R2 = OEt, R3 = OH, n = 1
14ab
14ac
:
18
19
:
20aa n = 1
:
: n = 2
20ab
14ae :
Ph
Ph
O
HO
O
O
O
Ph
Mn(OAc)3
AcOH
reflux
1a
+
N
Me
O
O
Ph
Ph
O
O
O
12d
13ad
21
Scheme 3.
Scheme 4.

1624
K. Asahi, H. Nishino / Tetrahedron 64 (2008) 1620e1634
Table 4
Oxidation of a mixture of 1,1-diphenylethene (1a) and cyclic diketones 16aec
O
O
O
O
O
R2
O
O
O
R2
R2
with manganese(III) acetatea
n
n
R1
R1
R1
R1
1
Mn(III)
heat
X
n
III
X
X
Mn
-Mn(II)
Entry
1
Cycloalkane
Molar
ratiob
Time
(min)
Product (yield,c %)
m
O
m
m
A
B
C
16a
n¼0
1:1.2:3
10
17aa (32)
19 (33)
18 (7)
20aa (19)
X = NR3, CH2, CMe2, O
m = 0-3, n = 1,2
AcOH
2
3
16b
16b
n¼1
n¼1
1:1.2:4
1:1.2:4
1
10
17ab (96)
17ab (43)
or H2O
R2
O
20ab (14)
21 (16)
5,19
O
O
n
4
16c
n¼1
1:1.5:4.5
0.5
17ac (84)
-H
Propellanes
R1
R1
X
6,14,21
3,8,10,13,17,18
a
The reaction of 1a (0.5 mmol) with 16 was carried out in glacial acetic
acid (20 mL) in the presence of manganese(III) acetate dihydrate at reflux
temperature. Before the reaction, the mixture was degassed under reduced
pressure for 30 min using an ultrasonicator followed by argon displacement.
AcOH
m
or H2O
D
Scheme 5.
b
Ratio of 1a/16/Mn(OAc)3.
Isolated yield based on the amount of 1a used.
c
oxoethyl)malonates.11,16 The enolate complex A would be
formed by the reaction of the cyclic 1,3-diones with manganese-
(III) acetate during the first stage. It is known that the
manganese(III)eenolate complex formation is the rate-deter-
mining step.8a,9c The enolate complex A easily oxidized the
electron-rich alkenes 1 via a weak interaction between com-
plex A and the alkene 1 such as an electron donoreacceptor-
like complex,9c giving the corresponding tertiary carbon
radicals B, which were rapidly oxidized by sufficient amounts
of manganese(III) acetate under the stated conditions. As a re-
sult, the carbocations C would be formed and cyclize at the
keto carbonyl oxygen of the cyclic 1,3-diones to produce the
thermodynamically more stable carbocations D. The cations
D would be allowed to intramolecularly cyclize at the carbonyl
oxygen of the most appropriate position to finally produce the
desired dioxapropellanes such as 3 and 8 by deprotonation.
The by-products 5, 6, 14, 19, and 21 were formed by the attack
of the acetate ion or water on cations C and D, however, the
reaction should be reversible. Accordingly, the dioxapropel-
lanes could be solely obtained when the dissolved molecular
oxygen in the solvent was completely removed by degassing
before the oxidation and the heating of the reaction mixture
was continued for 10 min after the oxidation.
heating after finishing the oxidation was not effective for the
propellane formation and a considerable amount of the bicy-
clic propellane precursors 14 was obtained, the acid-catalyzed
decomposition of the propellane 13ac was examined. When
the propellane 13ac was treated with 2 M HCl in a 1:1 mixture
of tetrahydrofuran and chloroform at reflux temperature, the
ring-opened bicyclic hydroxide 14ac was quantitatively ob-
tained (93% yield). Therefore, the propellanes 13 might be
sensitive to acidic media. We next investigated the forced
transformation of the bicyclic hydroxides 14 into the corre-
sponding propellanes 13. The reaction was carried out in dry
tetrahydrofuran using various Lewis acids, and the propellane
formation was eventually achieved (Table 5). The use of ethyl
aluminum dichloride or aluminum trichloride was effective for
the cyclization (Table 5, entries 1, 3, 9, and 10).
2.5. Reaction pathway
The proposed mechanism for the formation of the dioxa-
propellanes is outlined in Scheme 5. The manganese(III)-based
oxidative cycloadditionetandem cyclization could be ex-
plained by a similar mechanism for the reaction using 2-(2-
Table 5
Lewis acid-induced cyclization of propellane intermediates 14 and 21a
Entry
1
Intermediate
Lewis acid
Conditions
Recovery (%)
Propellane (yield,b %)
14aa
EtAlCl2 (4 equiv)
rt (30 min) then
Reflux (30 min)
rt (30 min) then
Reflux (30 min)
rt (5 h)
13aa (96)
2
14ab
EtAlCl2 (4 equiv)
13ab (29)
3
4
5
6
7
8
14ab
14ab
14ab
14ab
14ab
14ac
AlCl3 (4 equiv)
BF3$OEt2 (5 equiv)
FeCl3 (5 equiv)
CuCl2 (5 equiv)
TiCl4 (5 equiv)
EtAlCl2 (4 equiv)
31
13ab (53)
13ab (9)
Reflux (30 min)
Reflux (10 h)
55
52
25
13ab (24)
13ab (29)
13ab (49)
13ac (29)
Reflux (10 h)
rt (6 h) then 50e60 ꢁC (1 h)
rt (30 min) then
Reflux (30 min)
rt (5 h)
9
10
14ac
21
AlCl3 (4 equiv)
EtAlCl2 (4 equiv)
51
13ac (35)
17ab (93)
rt (30 min) then
Reflux (1 h)
a
The reaction of the intermediate 14 or 21 (0.1 mmol) was carried out in dry tetrahydrofuran (2 mL) in air.
Isolated yield based on the amount of the precursors 14 or 21 used.
b

K. Asahi, H. Nishino / Tetrahedron 64 (2008) 1620e1634
1625
3. Conclusion
synthesized by a similar condensation as described above
from the corresponding cycloalkane-1,3-diones or 4-hydroxy-
1-methyl-1H-quinolin-2-one.18 The 2-(3-oxopropyl)cycloal-
kane-1,3-diones 12aec, 3-(3-oxopropyl)-1H-quinolin-2-one
16b, and 3-(3-oxopropyl)coumarin 16c were produced by the
reaction of the corresponding cyclic 1,3-diones with 1-aryl-3-
dimethylaminopropan-1-ones (Mannich base) during the elim-
ination of dimethylamine.19
We have accomplished the unique and selective synthesis of
dioxapropellanes using the manganese(III)-based oxidation of
the oxoalkyl-substituted cycloalkane-1,3-diones in the presence
of alkenes 1. However, the propellane formation was limited to
the use of the alkenes such as 1,1-diarylethenes. Furthermore,
the ring size of the cycloalkanediones 7 was bigger, the yield
of the propellanes 8 was lower, and the production of spiroal-
kanes 9 were promoted. In addition, the oxopropyl-substituted
cycloalkanediones 12 resisted the propellane formation and the
bicyclic propellane precursors 14 were also isolated. The precur-
sors 14 could be eventually converted into the corresponding
propellanes 13 by the Lewis acid-mediated intramolecular cycli-
zation. To the best of our knowledge, the propellane synthesis
using the manganese(III)-based oxidative cyclization has never
been reported. This propellane formation may be adaptable to
various oxoalkyl-substituted cycloalkanediones.
4.3. Manganese(III)-based oxidation of a mixture of alkenes
1aef and triketones 2, 7, 12, 16 at reflux temperature
The general procedure for the oxidation is as follows. An
alkene 1 (0.5 mmol), triketone (0.6e1.5 mmol), and glacial
acetic acid (20 mL) were placed in a 50 mL flask. Before the
oxidation, the mixture was degassed under reduced pressure
for 30 min using an ultrasonicator and then filled with argon.
Manganese(III) acetate dihydrate (1.5e5.0 mmol) was quickly
added to the reaction mixture followed by heating under reflux
for 10 min (normally the brown color of manganese(III) disap-
peared within 1 min). The exact molar ratio of the alkene, trike-
tone, and oxidant is shown in Tables 1e4. The solvent was
removed in vacuo and the residue was triturated with water fol-
lowed by extraction with chloroform (10 mLꢂ3). The com-
bined extracts were dried over anhydrous magnesium sulfate
and then concentrated to dryness. The products were separated
by a silica gel TLC (Wakogel B-10) while eluting with chloro-
form. The products were further purified by recrystallization
from the appropriate solvents.
4. Experimental
4.1. General
The NMR spectra were recorded using a JNM EX300 FT
1
NMR spectrometer at 300 MHz for H and at 75 MHz for
13C, with tetramethylsilane as the internal standard. The chem-
ical shifts are reported in d values (ppm). The IR spectra of the
neat samples were measured by the ATR method using a Shi-
madzu 8400 FTIR spectrophotometer and MIRacle A, and
expressed in cmꢀ1. The EIMS spectra were recorded by a Shi-
madzu QP-5050A gas chromatographemass spectrometer at
the ionizing voltage of 70 eV. The high resolution mass spectra
were measured at the Institute for Materials Chemistry and
Engineering, KyushuUniversity, Fukuoka, Japan. The elemental
analyses were performed at the Analytical Center of Kumamoto
University, Kumamoto, Japan. Manganese(II) acetate tetrahy-
drate was purchased from Wako Pure Chemical Ind., Ltd. Man-
ganese(III) acetate dihydrate, Mn(OAc)3$2H2O, was prepared
according to the method described in the literature.8bem,9 The
alkenes 1 were synthesized according to the literature,7c,8eem
except for 1g and 1h, which were purchased from Tokyo Kasei
Co., Ltd.
4.3.1. 3-Benzyl-8,11,11-triphenyl-3-aza-7,12-dioxatricyclo-
[4.3.3.01,6]dodec-8-en-2-one (3aa)
Rf¼0.22 (chloroform); colorless oil; IR (neat) n 1647
(C]O); 1H NMR (300 MHz, CDCl3) d 7.52e7.50 (2H,
m, arom. H), 7.49e7.41 (2H, m, arom. H), 7.39e7.12 (13H,
m, arom. H), 7.02e6.97 (2H, m, arom. H), 6.86e6.81 (2H, m,
arom. H), 5.19 (1H, s, H-9), 4.66 (1H, d, J¼14.9 Hz, PheCH2),
4.44 (1H, d, J¼14.9 Hz, PheCH2), 3.59 (1H, d, J¼13.4 Hz,
H-10), 3.28 (1H, ddd, J¼12.9, 10.5, 2.9 Hz, H-4), 3.13 (1H,
ddd, J¼12.9, 4.8, 3.9 Hz, H-4), 2.97 (1H, d, J¼13.4 Hz,
H-10), 2.49 (1H, ddd, J¼13.6, 4.8, 2.9 Hz, H-5), 2.14 (1H,
ddd, J¼13.6, 10.5, 3.9 Hz, H-5); 13C NMR (75 MHz, CDCl3)
d 170.5 (C]O), 156.3 (C-8), 146.1, 144.4, 136.5, 129.2 (4C,
arom. C), 128.7, 128.6, 128.2, 127.74, 127.65, 127.5, 127.4,
126.8, 126.3, 125.4, 125.23, 125.16 (20C, arom. CH), 115.9
(C-6), 99.0, 98.9 (1C, C-9), 89.8 (C-11), 63.8 (C-1), 50.1
(PheCH2), 47.5 (C-10), 42.7 (C-4), 33.7 (C-5). FAB HRMS
(acetoneeNBA) calcd for C34H30NO3 500.2226 (Mþ1). Found
500.2229.
4.2. Preparation of 3-(2-oxoethyl)piperidine-2,4-diones and
their analogs
The 3-(2-oxoethyl)piperidine-2,4-dione derivatives 2aei
were prepared by the reaction of the corresponding piperi-
dine-2,4-diones with 2-bromoethanones in the presence of po-
tassium carbonate in ethanol (see Supplementary data). The
piperidinediones were synthesized by the Michael addition
of alkyl acrylates with primary amines followed by condensa-
tion with alkyl malonyl chlorides and subsequent Dieckmann
condensation in the presence of sodium ethoxide, and then de-
carboxylation by using 10% aqueous sulfuric acid at reflux
temperature.8b,17 The 2-(2-oxoethyl)cycloalkane-1,3-diones
7aeg and 3-(2-oxoethyl)-1H-quinolin-2-one 16a were also
4.3.2. 3-Benzyl-11,11-bis(4-methylphenyl)-8-phenyl-3-aza-
7,12-dioxatricyclo[4.3.3.01,6]dodec-8-en-2-one (3ba)
Rf¼0.38 (chloroform); colorless prisms; mp 167.0 ꢁC; IR
(neat)
n
1647 (C]O); 1H NMR (300 MHz, CDCl3)
d 7.37e7.35 (2H, m, arom. H), 7.29e7.12 (12H, m, arom. H),
7.07e7.04 (2H, m, arom. H), 6.80e6.77 (2H, m, arom. H),
5.19 (1H, s, H-9), 4.66 (1H, d, J¼14.7 Hz, PheCH2), 4.41

1626
K. Asahi, H. Nishino / Tetrahedron 64 (2008) 1620e1634
(1H, d, J¼14.7 Hz, PheCH2), 3.53 (1H, d, J¼13.4 Hz, H-10),
3.27 (1H, ddd, J¼12.3, 10.8, 2.6 Hz, H-4), 3.11 (1H, ddd,
J¼12.3, 5.5, 3.9 Hz, H-4), 2.95 (1H, d, J¼13.4 Hz, H-10),
2.45 (1H, ddd, J¼13.6, 5.5, 2.6 Hz, H-5), 2.25 (3H, s, CH3),
2.12 (1H, ddd, J¼13.6, 10.8, 3.9 Hz, H-5), 1.98 (3H, s, CH3);
13C NMR (75 MHz, CDCl3) d 170.5 (C]O), 156.2 (C-8),
143.3, 141.6, 136.5, 136.3, 135.6, 129.3 (6C, arom. C), 128.7,
128.6, 128.5, 128.1, 127.6, 127.3, 125.3, 125.2, 125.1 (18C,
arom. CH), 115.8 (C-6), 99.1 (C-9), 89.6 (C-11), 63.8 (C-1),
50.0 (PheCH2), 47.5 (C-10), 42.6 (C-4), 33.7 (C-5), 20.8,
20.5 (2C, CH3). Anal. Calcd for C36H33NO3: C, 81.95; H,
6.30; N, 2.65. Found: C, 82.17; H, 6.18; N, 2.60.
arom. H), 7.08e6.91 (2H, m, arom. H), 6.73e6.66 (2H, m,
arom. H), 5.19 (1H, s, H-9), 4.67 (1H, d, J¼14.9 Hz,
PheCH2), 4.47 (1H, d, J¼14.9 Hz, PheCH2), 3.52 (1H, d,
J¼13.6 Hz, H-10), 3.31 (1H, ddd, J¼13.0, 10.6, 2.6 Hz,
H-4), 3.16 (1H, ddd, J¼13.0, 4.6, 3.7 Hz, H-4), 2.91 (1H, d,
J¼13.6 Hz, H-10), 2.50 (1H, ddd, J¼13.6, 4.6, 2.6 Hz, H-5),
2.13 (1H, ddd, J¼13.6, 10.6, 3.7 Hz, H-5); 13C NMR
(75 MHz, CDCl3) d 170.3 (C]O), 163.3, 163.0, 160.0,
159.8 (2C, arom. C), 156.5 (C-8), 141.9, 141.8, 140.2,
140.1, 136.5 (3C, arom. C), 129.1 (arom. CH), 129.0 (arom.
C), 128.7, 128.4, 128.1, 128.0, 127.9, 127.7, 127.5, 127.2,
127.1, 127.0, 126.9, 125.1 (13C, arom. CH), 116.0 (C-6),
115.2, 114.9, 114.5, 114.3 (4C, arom. CH), 98.9, 98.8 (1C,
C-9), 89.1 (C-11), 63.9 (C-1), 50.2 (PheCH2), 47.8 (C-10),
42.7 (C-4), 33.7 (C-5). FAB HRMS (acetoneeNBA) calcd
for C34H28F2NO3 536.2037 (Mþ1). Found 536.2036.
4.3.3. 3-Benzyl-11,11-bis(4-methoxyphenyl)-8-phenyl-3-
aza-7,12-dioxatricyclo[4.3.3.01,6]dodec-8-en-2-one (3ca)
Rf¼0.33 (chloroform); colorless oil; IR (neat) n 1649
1
(C]O); H NMR (300 MHz, CDCl3) d 7.46e7.43 (2H, m,
arom. H), 7.29e7.13 (12H, m, arom. H), 6.81e6.78 (2H, m,
arom. H), 6.55e6.52 (2H, m, arom. H), 5.21 (1H, s, H-9),
4.67 (1H, d, J¼14.7 Hz, PheCH2), 4.45 (1H, d, J¼14.7 Hz,
PheCH2), 3.73 (3H, s, OCH3), 3.48 (3H, s, OCH3), 3.45
(1H, d, J¼13.4 Hz, H-10), 3.29 (1H, ddd, J¼12.8, 10.4,
2.8 Hz, H-4), 3.14 (1H, ddd, J¼12.8, 5.0, 4.0 Hz, H-4), 2.95
(1H, d, J¼13.4 Hz, H-10), 2.47 (1H, ddd, J¼13.6, 5.0,
2.8 Hz, H-5), 2.14 (1H, ddd, J¼13.6, 10.4, 4.0 Hz, H-5); 13C
NMR (75 MHz, CDCl3) d 170.6 (C]O), 158.3, 157.9, 156.2
(3C, arom. C, C-8), 138.4, 136.8, 136.5, 129.4 (4C, arom.
C), 128.7, 128.6, 127.7, 127.6, 127.4, 126.8, 126.7, 125.3
(14C, arom. CH), 115.9 (C-6), 113.4, 112.9 (4C, arom. CH),
99.24, 99.17 (1C, C-9), 89.5 (C-11), 64.0 (C-1), 55.11,
55.08, 54.97, 54.95 (2C, OCH3), 50.1 (PheCH2), 47.9
(C-10), 42.7 (C-4), 33.7 (C-5). FAB HRMS (acetoneeNBA)
calcd for C36H34NO5 560.2437 (Mþ1). Found 560.2438.
4.3.6. 3-Benzyl-8-(4-methylphenyl)-11,11-diphenyl-3-aza-
7,12-dioxatricyclo[4.3.3.01,6]dodec-8-en-2-one (3ab)
Rf¼0.44 (chloroform); colorless microcrystals (from ethyl
acetateehexane); mp 128e129 ꢁC; IR (KBr) n 1636 (C]O);
1H NMR (300 MHz, CDCl3) d 7.52e7.49 (2H, m, arom. H),
7.41e7.38 (2H, m, arom. H), 7.35e7.11 (12H, m, arom. H),
7.03e6.98 (2H, m, arom. H), 6.88e6.83 (1H, m, arom. H), 5.12
(1H, s, H-9), 4.65 (1H, d, J¼14.9 Hz, PheCH2), 4.43 (1H, d,
J¼14.9 Hz, PheCH2), 3.58 (1H, d, J¼13.4 Hz, H-10), 3.28
(1H, ddd, J¼12.7, 10.6, 2.4 Hz, H-4), 3.11 (1H, ddd, J¼12.7,
5.0, 3.9 Hz, H-4), 2.97 (1H, d, J¼13.4 Hz, H-10), 2.48 (1H,
ddd, J¼13.6, 5.0, 2.4 Hz, H-5), 2.28 (3H, s, CH3), 2.12 (1H,
ddd, J¼13.6, 10.6, 3.9 Hz, H-5); 13C NMR (75 MHz, CDCl3)
d 170.7 (C]O), 156.6 (C-8), 146.3, 144.6, 138.8, 136.6 (4C,
arom. C), 128.7, 128.5, 128.2, 127.7, 127.6, 127.4, 126.9
(arom. CH), 126.6 (arom. C), 126.3, 125.4, 125.3 (arom. CH),
115.9 (C-6), 98.2 (C-9), 89.8 (C-11), 63.8 (C-1), 50.2
(PheCH2), 47.6 (C-10), 42.8 (C-4), 33.7 (C-5), 21.3 (CH3).
Anal. Calcd for C35H31NO3: C, 81.84; H, 6.08; N, 2.73. Found:
C, 82.00; H, 6.26; N, 2.70. FAB HRMS (acetoneeNBA) calcd
for C35H32NO3 514.2382 (Mþ1). Found 514.2333.
4.3.4. 3-Benzyl-11,11-bis(4-chlorophenyl)-8-phenyl-3-aza-
7,12-dioxatricyclo[4.3.3.01,6]dodec-8-en-2-one (3da)
Rf¼0.28 (chloroform); colorless oil; IR (neat) n 1643
1
(C]O); H NMR (300 MHz, CDCl3) d 7.42e7.39 (2H, m,
arom. H), 7.31e7.14 (14H, m, arom. H), 6.99e6.96 (2H, m,
arom. H), 5.17 (1H, s, H-9), 4.68 (1H, d, J¼14.9 Hz, PheCH2),
4.46 (1H, d, J¼14.9 Hz, PheCH2), 3.51 (1H, d, J¼13.6 Hz,
H-10), 3.32 (1H, ddd, J¼12.7, 11.0, 2.4 Hz, H-4), 3.16 (1H,
ddd, J¼12.7, 5.3, 4.0 Hz, H-4), 2.89 (1H, d, J¼13.6 Hz,
H-10), 2.51 (1H, ddd, J¼13.6, 5.3, 2.4 Hz, H-5), 2.11 (1H,
ddd, J¼13.6, 11.0, 4.0 Hz, H-5); 13C NMR (75 MHz, CDCl3)
d 170.1 (C]O), 156.6 (C-8), 144.2, 142.7, 136.4, 133.0,
132.5, 129.1 (6C, arom. C), 128.7, 128.5, 128.0, 127.8, 127.7,
127.6, 126.8, 126.6, 125.1 (18C, arom. CH), 116.0 (C-6),
98.9, 98.8 (1C, C-9), 88.9 (C-11), 63.8 (C-1), 50.2 (PheCH2),
47.5 (C-10), 42.7 (C-4), 33.7 (C-5). FAB HRMS (acetonee
NBA) calcd for C34H28Cl2NO3 568.1446 (Mþ1). Found
568.1432.
4.3.7. 3-Benzyl-8-(4-chlorophenyl)-11,11-diphenyl-3-aza-
7,12-dioxatricyclo[4.3.3.01,6]dodec-8-en-2-one (3ac)
Rf¼0.53 (chloroform); colorless needles (from ethyl aceta-
1
teehexane); mp 174e175 ꢁC; IR (KBr) n 1645 (C]O); H
NMR (300 MHz, CDCl3) d 7.51e7.48 (2H, m, arom. H),
7.39e7.37 (2H, m, arom. H), 7.27e7.14 (12H, m, arom. H),
7.02e6.97 (2H, m, arom. H), 6.87e6.82 (1H, m, arom. H), 5.18
(1H, s, H-9), 4.65 (1H, d, J¼14.7 Hz, PheCH2), 4.45 (1H, d,
J¼14.7 Hz, PheCH2), 3.61 (1H, d, J¼13.4 Hz, H-10), 3.26
(1H, ddd, J¼13.0, 10.1, 2.9 Hz, H-4), 3.15 (1H, ddd, J¼13.0,
5.1, 4.0 Hz, H-4), 2.91 (1H, d, J¼13.4 Hz, H-10), 2.47 (1H,
ddd, J¼13.8, 5.1, 2.9 Hz, H-5), 2.16 (1H, ddd, J¼13.8, 10.1,
4.0 Hz, H-5); 13C NMR (75 MHz, CDCl3) d 170.3 (C]O),
155.3 (C-8), 146.1, 144.3, 136.5, 134.5 (4C, arom. C), 128.7,
128.2, 128.03, 127.96, 127.8 (arom. CH), 127.7 (arom. C),
127.6, 127.5, 126.9, 126.6, 126.4, 125.4, 125.1 (arom. CH),
116.0 (C-6), 99.54, 99.51 (1C, C-9), 89.9 (C-11), 63.9 (C-1),
50.2 (PheCH2), 47.5 (C-10), 42.7 (C-4), 33.7 (C-5). Anal.
4.3.5. 3-Benzyl-11,11-bis(4-fluorophenyl)-8-phenyl-3-aza-
7,12-dioxatricyclo[4.3.3.01,6]dodec-8-en-2-one (3ea)
Rf¼0.42 (chloroform); colorless oil; IR (neat) n 1649
1
(C]O); H NMR (300 MHz, CDCl3) d 7.47e7.14 (14H, m,

K. Asahi, H. Nishino / Tetrahedron 64 (2008) 1620e1634
1627
Calcd for C34H28ClNO3: C, 76.47; H, 5.28; N, 2.62. Found: C,
76.65; H, 5.32; N, 2.57. FAB HRMS (acetoneeNBA) calcd for
C34H29ClNO3 534.1836 (Mþ1). Found 534.1837.
CDCl3) d 170.1 (C]O), 156.1 (C-8), 146.2, 144.3, 129.3
(3C, arom. C), 128.6, 128.1, 127.7, 127.4, 126.7, 126.2,
125.4, 125.1 (15C, arom. CH), 115.8 (C-6), 99.1, 98.9 (1C,
C-9), 89.7 (C-11), 63.7 (C-1), 48.7 (NeCH2CH2CH3), 47.5
(C-10), 43.4 (C-4), 33.7 (C-5), 20.5 (NeCH2CH2CH3), 11.1,
11.0 (1C, NeCH2CH2CH3). Anal. Calcd for C30H29NO3: C,
79.80; H, 6.47; N, 3.10. Found: C, 79.73; H, 6.47; N, 3.06.
FAB HRMS (acetoneeNBA) calcd for C30H30NO3 452.2226
(Mþ1). Found 452.2222.
4.3.8. 3-Methyl-8,11,11-triphenyl-3-aza-7,12-dioxatricyclo-
[4.3.3.01,6]dodec-8-en-2-one (3ad)
Rf¼0.20 (chloroform); colorless microcrystals (from ethyl
1
acetateehexane); mp 148.0 ꢁC; IR (neat) n 1636 (C]O); H
NMR (300 MHz, CDCl3) d 7.51e7.48 (2H, m, arom. H),
7.38e7.35 (2H, m, arom. H), 7.26e7.11 (8H, m, arom. H),
7.01e6.96 (2H, m, arom. H), 6.85e6.80 (1H, m, arom. H), 5.12
(1H, s, H-9), 3.55 (1H, d, J¼13.4 Hz, H-10), 3.36 (1H, ddd,
J¼12.7, 10.5, 2.8 Hz, H-4), 3.14 (1H, ddd, J¼12.7, 5.0,
4.0 Hz, H-4), 2.90 (3H, s, NeCH3), 2.85 (1H, d, J¼13.4 Hz,
H-10), 2.55 (1H, ddd, J¼13.4, 5.0, 2.8 Hz, H-5), 2.25 (1H,
ddd, J¼13.4, 10.6, 4.0 Hz, H-5); 13C NMR (75 MHz, CDCl3)
d 170.3 (C]O), 156.0 (C-8), 146.1, 144.3, 129.2 (3C, arom.
C), 128.6, 128.0, 127.6, 127.4, 126.8, 126.2, 125.4, 125.3,
125.1 (15C, arom. CH), 115.8 (C-6), 99.1, 98.9 (1C, C-9),
89.8 (C-11), 63.4 (C-1), 47.5 (C-10), 45.4 (C-4), 34.9
(NeCH3), 33.2 (C-5). Anal. Calcd for C28H25NO3: C, 79.41;
H, 5.95; N, 3.31. Found: C, 79.39; H, 5.95; N, 3.26. FAB
HRMS (acetoneeNBA) calcd for C28H25NO3 423.1834 (M).
Found 423.1830.
4.3.11. 3-Isopropyl-8,11,11-triphenyl-3-aza-7,12-
dioxatricyclo[4.3.3.01,6]dodec-8-en-2-one (3ag)
Rf¼0.29 (chloroform); colorless needles (from chloroforme
hexane); mp 137 ꢁC; IR (neat) n 1632 (C]O); 1H NMR
(300 MHz, CDCl3) d 7.53e7.50 (2H, m, arom. H), 7.41e7.38
(2H, m, arom. H), 7.25e7.11 (8H, m, arom. H), 7.01e6.95
(2H, m, arom. H), 6.84e6.79 (1H, m, arom. H), 5.14 (1H, s,
H-9), 4.79 (1H, sep, J¼6.8 Hz, NeCH(CH3)2), 3.55 (1H, d,
J¼13.4 Hz, H-10), 3.19e3.12 (2H, m, H-4), 2.87 (1H, d,
J¼13.4 Hz, H-10), 2.54 (1H, ddd, J¼13.4, 4.8, 2.9 Hz, H-5),
2.14 (1H, ddd, J¼13.4, 8.6, 5.5 Hz, H-5), 1.03 (3H,
d, J¼6.8 Hz, NeCH(CH3)2), 1.00 (3H, d, J¼6.8 Hz,
NeCH(CH3)2); 13C NMR (75 MHz, CDCl3) d 169.7 (C]O),
156.1 (C-8), 146.3, 144.5, 129.4 (3C, arom. C), 128.7, 128.2,
127.7, 127.5, 126.8, 126.2, 125.4, 125.2, 125.1 (15C, arom.
CH), 115.7 (C-6), 99.0 (C-9), 89.8 (C-11), 63.9 (C-1), 47.7
(C-10), 44.0 (NeCH(CH3)2), 36.3 (C-4), 34.1 (C-5), 19.3,
19.2 (2C, NeCH(CH3)2). Anal. Calcd for C30H29NO3: C,
79.80; H, 6.47; N, 3.10. Found: C, 79.83; H, 6.71; N, 3.14.
FAB HRMS (acetoneeNBA) calcd for C30H29NO3 452.2226
(Mþ1). Found 452.2189.
4.3.9. 3-Ethyl-8,11,11-triphenyl-3-aza-7,12-dioxatricyclo-
[4.3.3.01,6]dodec-8-en-2-one (3ae)
Rf¼0.20 (chloroform); colorless microcrystals (from chloro-
formehexane); mp 137e138 ꢁC; IR (neat) n 1641 (C]O); 1H
NMR (300 MHz, CDCl3) d 7.51e7.49 (2H, m, arom. H),
7.39e7.37 (2H, m, arom. H), 7.30e7.12 (8H, m, arom. H),
7.02e6.96 (2H, m, arom. H), 6.85e6.80 (1H, m, arom. H), 5.13
(1H, s, H-9), 3.55 (1H, d, J¼13.4 Hz, H-10), 3.38 (2H, q,
J¼7.2 Hz, NeCH2CH3), 3.35e3.31 (1H, m, H-4), 3.18 (1H,
ddd, J¼12.8, 4.8, 3.9 Hz, H-4), 2.86 (1H, d, J¼13.4 Hz,
H-10), 2.56 (1H, ddd, J¼13.6, 4.8, 2.8 Hz, H-5), 2.23 (1H,
ddd, J¼13.6, 10.5, 3.9 Hz, H-5), 1.04 (3H, t, J¼7.2 Hz,
NeCH2CH3); 13C NMR (75 MHz, CDCl3) d 169.8 (C]O),
156.0 (C-8), 146.2, 144.4, 129.3 (3C, arom. C), 128.6, 128.1,
127.7, 127.4, 126.8, 126.2, 125.4, 125.1 (15C, arom. CH),
115.8 (C-6), 99.1, 98.9 (1C, C-9), 89.8 (C-11), 63.6 (C-1),
47.5 (C-10), 42.8 (C-4), 42.0 (NeCH2CH3), 33.7 (C-5), 12.4,
12.2 (1C, NeCH2CH3). Anal. Calcd for C29H27NO3: C,
79.61; H, 6.22; N, 3.20. Found: C, 79.46; H, 6.27; N, 3.11.
4.3.12. 3,8,11,11-Tetraphenyl-3-aza-7,12-dioxatricyclo-
[4.3.3.01,6]dodec-8-en-2-one (3ah)
Rf¼0.29 (chloroform); colorless microcrystals (from chloro-
1
formehexane); mp 204.0 ꢁC; IR (neat) n 1655 (C]O); H
NMR (300 MHz, CDCl3) d 7.54e7.52 (2H, m, arom. H),
7.44e7.42 (2H, m, arom. H), 7.39e7.17 (13H, m, arom. H),
7.16e6.99 (2H, m, arom. H), 6.87e6.82 (1H, m, arom. H), 5.21
(1H, s, H-9), 3.78 (1H, ddd, J¼12.8, 10.5, 2.8 Hz, H-4), 3.64e
3.60 (1H, m, H-4), 3.59 (1H, d, J¼13.4 Hz, H-10), 3.03 (1H,
d, J¼13.4 Hz, H-10), 2.69 (1H, br d, J¼13.6 Hz, H-5), 2.44
(1H, ddd, J¼13.6, 10.5, 3.3 Hz, H-5); 13C NMR (75 MHz,
CDCl3) d 170.0 (C]O), 156.5 (C-8), 146.1, 144.3, 142.5,
129.2 (4C, arom. C), 128.9, 128.8, 128.2, 127.8, 127.5, 126.9,
126.6, 126.3, 125.4, 125.25, 125.17 (20C, arom. CH), 115.8
(C-6), 98.9, 98.7 (1C, C-9), 90.0 (C-11), 64.3 (C-1), 47.7
(C-10), 46.9 (C-4), 34.2 (C-5). Anal. Calcd for C33H27NO3: C,
81.63; H, 5.60; N, 2.88. Found: C, 81.67; H, 5.61; N, 2.87.
FAB HRMS (acetoneeNBA) calcd for C33H28NO3 486.2069
(Mþ1). Found 486.2098.
4.3.10. 3-Propyl-8,11,11-triphenyl-3-aza-7,12-dioxatricyclo-
[4.3.3.01,6]dodec-8-en-2-one (3af)
Rf¼0.22 (chloroform); colorless needles (from ethyl ace-
tateehexane); mp 137 ꢁC; IR (neat) n 163.8 (C]O); 1H NMR
(300 MHz, CDCl3) d 7.52e7.49 (2H, m, arom. H), 7.40e7.37
(2H, m, arom. H), 7.26e7.14 (8H, m, arom. H), 7.01e6.97
(2H, m, arom. H), 6.85e6.82 (1H, m, arom. H), 5.13 (1H, s,
H-9), 3.55 (1H, d, J¼13.4 Hz, H-10), 3.42e3.15 (4H, m,
NeCH2CH2CH3, H-4), 2.84 (1H, d, J¼13.4 Hz, H-10), 2.56
(1H, br d, J¼13.6 Hz, H-5), 2.22 (1H, ddd, J¼13.6, 10.5,
3.9 Hz, H-5), 1.49 (2H, sex, J¼7.2 Hz, NeCH2CH2CH3),
0.83 (3H, t, J¼7.2 Hz, NeCH2CH2CH3); 13C NMR (75 MHz,
4.3.13. 3,8-Di-tert-butyl-11,11-dinaphthalen-2-yl-3-aza-
7,12-dioxatricyclo[4.3.3.01,6]dodec-8-en-2-one (3fi)
Rf¼0.23 (chloroform); colorless prisms (from diethyl ethere
hexane); mp 234e235 ꢁC; IR (KBr) n 1649 (C]O); 1H NMR
(300 MHz, CDCl3) d 8.05e7.38 (14H, m, arom. H), 4.62 (1H,

1628
K. Asahi, H. Nishino / Tetrahedron 64 (2008) 1620e1634
s, H-9), 3.70 (1H, d, J¼13.7 Hz, H-10), 3.40 (1H, ddd, J¼13.2,
4.9, 3.7 Hz, H-4), 3.22 (1H, ddd, J¼13.2, 10.1, 2.0 Hz, H-4),
2.89 (1H, d, J¼13.7 Hz, H-10), 2.43 (1H, ddd, J¼13.4, 4.9,
2.0 Hz, H-5), 2.18 (1H, ddd, J¼13.4, 10.1, 3.7 Hz, H-5), 1.37
(9H, s, NeC(CH3)3), 0.51 (9H, s, C(CH3)3); 13C NMR
(75 MHz, CDCl3) d 172.2 (C]O), 167.5 (C-8), 144.3, 141.9,
132.9, 132.6, 132.4, 132.1 (6C, arom. C), 128.2, 128.1, 128.0,
127.44, 127.39, 127.3, 126.0, 125.9, 125.8, 125.7, 125.5,
124.5, 124.0, 122.9 (14C, arom. CH), 115.7 (C-6), 96.3 (C-9),
89.7 (C-11), 65.4 (C-1), 57.5 (NeC(CH3)3), 46.5 (C-10), 39.6
(C-4), 35.0 (C-5), 31.5 (C(CH3)3), 28.4 (9C, NeC(CH3)3),
27.0 (9C, C(CH3)3). Anal. Calcd for C37H39NO3: C, 81.43; H,
7.20; N, 2.57. Found: C, 81.15; H, 7.35; N, 2.52.
7.01e6.96 (2H, m, arom. H), 6.87e6.82 (1H, m, arom. H), 5.05
(1H, s, H-9), 3.46 (1H, d, J¼13.2 Hz, H-10), 2.65 (1H, d,
J¼13.2 Hz, H-10), 2.56 (1H, d, J¼14.5 Hz, H-5), 2.35 (1H,
d, J¼15.6 Hz, H-3), 2.26 (1H, d, J¼15.6 Hz, H-3), 2.20 (1H,
d, J¼14.5 Hz, H-5), 1.05 (3H, s, CH3), 0.95 (3H, s, CH3);
13C NMR (75 MHz, CDCl3) d 209.9 (C]O), 155.1 (C-8),
146.7, 144.8, 129.6 (3C, arom. C), 128.7, 128.2, 127.8, 127.6,
126.8, 126.2, 125.3, 125.0 (15C, arom. CH), 118.3 (C-6), 98.8,
98.6 (1C, C-9), 89.1 (C-11), 67.2 (C-1), 51.2 (C-3), 47.0 (C-5),
46.6 (C-10), 32.4 (C-4), 30.7, 30.6, 27.5, 27.3 (2C, CH3). Anal.
Calcd for C30H28O3: C, 82.54; H, 6.46. Found: C, 82.29;
H, 6.45.
4.3.17. 8,11,11-Triphenyl-7,12-dioxatricyclo[4.3.3.01,6]-
dodec-8-en-2-one (8ab)
4.3.14. 8-Benzyl-4,4,12-triphenyl-8-aza-2,3,11-
trioxatricyclo[4.4.3.01,6]tridec-12-en-7-one (4aa)
Rf¼0.62 (chloroform); colorless microcrystals (from diethyl
ether); mp 136 ꢁC; IR (neat) n 1703 (C]O); 1H NMR
(300 MHz, CDCl3) d 7.51e7.48 (2H, m, arom. H), 7.38e7.35
(2H, m, arom. H), 7.28e7.16 (8H, m, arom. H), 7.03e6.98
(2H, m, arom. H), 6.87e6.82 (1H, m, arom. H), 4.89 (1H, s,
H-9), 3.38 (1H, d, J¼13.2 Hz, H-10), 2.75 (1H, d, J¼13.2 Hz,
H-10), 2.58e2.50 (2H, m, H-3, H-5), 2.36e2.25 (1H, m,
H-5), 2.05e1.86 (3H, m, H-3, H-4); 13C NMR (75 MHz,
CDCl3) d 209.4 (C]O), 157.4 (C-8), 146.4, 144.3, 129.4
(3C, arom. C), 128.9, 128.2, 127.8, 127.5, 126.9, 126.4,
125.7, 125.4, 125.2 (15C, arom. CH), 118.1 (C-6), 97.33,
97.28 (1C, C-9), 89.2 (C-11), 68.9 (C-1), 46.0 (C-10), 36.8
(C-5), 33.8 (C-3), 17.5 (C-4). Anal. Calcd for C28H24O3: C,
82.33; H, 5.92. Found: C, 82.36; H, 5.97.
Rf¼0.32 (chloroform); colorless microcrystals (from diethyl
ether); mp 166.5 ꢁC; IR (neat) n 1639 (C]O); 1H NMR
(300 MHz, CDCl3) d 7.57e7.54 (1H, m, arom. H), 7.43e7.12
(18H, m, arom. H), 5.13 (1H, s, H-13), 4.71 (1H, d,
J¼14.9 Hz, PheCH2), 4.37 (1H, d, J¼14.9 Hz, PheCH2),
3.86 (1H, d, J¼14.3 Hz, H-5), 3.38 (1H, ddd, J¼12.7, 11.8,
2.8 Hz, H-9), 3.11 (1H, ddd, J¼12.7, 4.6, 3.5 Hz, H-9), 2.69
(1H, d, J¼14.3 Hz, H-5), 2.23 (1H, ddd, J¼13.6, 3.5, 2.8 Hz,
H-10), 1.95 (1H, ddd, J¼13.6, 11.8, 4.6 Hz, H-10); 13C NMR
(75 MHz, CDCl3) d 169.3 (C]O), 156.3 (C-12), 146.8,
143.7, 136.3, 129.3 (4C, arom. C), 129.1, 128.7, 128.34,
128.27, 128.0, 127.7, 127.6, 127.1, 127.0, 125.42, 125.35,
125.2 (20C, arom. CH), 111.8 (C-1), 100.5, 100.4 (1C, C-13),
86.0 (C-4), 54.7 (C-6), 50.6 (PheCH2), 41.4 (C-9), 37.1
(C-5), 27.9 (C-10). Positive FABMS (acetoneeNBA) m/z 516
(Mþ1). Anal. Calcd for C34H29NO4: C, 79.20; H, 5.67; N,
2.72. Found: C, 79.33; H, 5.60; N, 2.74.
4.3.18. 8-Naphthalen-2-yl-11,11-diphenyl-7,12-
dioxatricyclo[4.3.3.01,6]dodec-8-en-2-one (8ac)
Rf¼0.62 (chloroform); colorless needles (from chloroforme
diethyl ether); mp 161 ꢁC; IR (KBr) n 1703 (C]O); 1H NMR
(300 MHz, CDCl3) d 7.79e6.70 (17H, m, arom. H), 5.02 (1H,
s, H-9), 3.42 (1H, d, J¼13.4 Hz, H-10), 2.77 (1H, d,
J¼13.4 Hz, H-10), 2.63e2.49 (2H, m, H-3, H-5), 2.37e2.26
(1H, m, H-5), 2.09e1.97 (1H, m, H-3), 1.90e1.87 (2H, m,
H-4); 13C NMR (75 MHz, CDCl3) d 209.2 (C]O), 157.3
(C-8), 146.3, 144.2, 133.3, 132.7 (4C, arom. C), 128.4, 128.2,
127.5, 127.4, 126.9 (arom. CH), 126.6 (arom. C), 126.4,
126.3, 126.2, 125.6, 125.2, 124.6, 123.0 (arom. CH), 118.1
(C-6), 98.1 (C-9), 89.2 (C-11), 68.9 (C-1), 46.1 (C-10), 36.7
(C-5), 33.8 (C-3), 17.4 (C-4). Anal. Calcd for C32H26O3: C,
83.82; H, 5.72. Found: C, 83.59; H, 5.51.
4.3.15. 1-Benzyl-3-(2-acetoxy-2,2-diphenylethyl)-3-(2-oxo-
2-phenylethyl)piperidine-2,4-dione (5)
Rf¼0.20 (diethyl etherehexane, 1:1, v/v); colorless micro-
crystals (from ethyl acetateehexane); mp 182e183 ꢁC; IR
(neat) n 1742, 1719, 1682, 1647 (C]O), 1221 (Ac); 1H NMR
(300 MHz, CDCl3) d 7.60e7.24 (20H, m, arom. H), 4.98 (1H,
d, J¼14.9 Hz, PheCH2), 3.90 (1H, d, J¼14.9 Hz, PheCH2),
3.62 (2H, s, CH2), 3.52e3.34 (4H, m, H-6, CH2), 2.82e2.67
(2H, m, H-5), 2.12 (3H, s, Ac); 13C NMR (75 MHz, CDCl3)
d 207.6, 197.5, 171.3, 169.5 (4C, C]O), 145.1, 144.3, 136.5,
135.8 (4C, arom. C), 133.2, 128.6, 128.6, 128.4, 128.3, 128.1,
128.0, 127.5, 127.2, 127.1, 125.4 (20C, arom. CH), 83.9
(Ph2pC), 56.2 (C-3), 50.8 (PheCH2), 46.4 (CH2), 41.4
(C-6, CH2), 37.1 (C-5), 22.3 (Ac). Anal. Calcd for
C34H29NO4: C, 77.26; H, 5.94; N, 2.50. Found: C, 76.98; H,
5.95; N, 2.54.
4.3.19. 9,12,12-Triphenyl-8,13-dioxatricyclo[5.3.3.01,7]-
tridec-9-en-2-one (8ad)
Rf¼0.78 (chloroform); colorless microcrystals (from diethyl
ether); mp 143 ꢁC; IR (KBr) n 1703 (C]O); 1H NMR
(300 MHz, CDCl3) d 7.80e7.77 (1H, m, arom. H), 7.55e7.09
(11H, m, arom. H), 6.99e6.94 (2H, m, arom. H), 6.84e6.79
(1H, m, arom. H), 4.83 (1H, s, H-10), 3.25 (1H, d,
J¼13.4 Hz, H-11), 3.05 (1H, d, J¼13.4 Hz, H-11), 2.87 (1H,
ddd, J¼13.0, 11.2, 3.1 Hz, H-6), 2.75e2.69 (1H, m, H-6),
2.33e2.27 (1H, m, H-3), 1.79e1.66 (4H, m, H-4, H-5),
1.46e1.35 (1H, m, H-3); 13C NMR (75 MHz, CDCl3) d 209.5
4.3.16. 4,4-Dimethyl-8,11,11-triphenyl-7,12-dioxatricyclo-
[4.3.3.01,6]dodec-8-en-2-one (8aa)
Rf¼0.66 (chloroform); colorless microcrystals (from chloro-
1
formehexane); mp 165.0 ꢁC; IR (neat) n 1693 (C]O); H
NMR (300 MHz, CDCl3) d 7.48e7.52 (2H, m, arom. H),
7.39e7.36 (2H, m, arom. H), 7.28e7.13 (8H, m, arom. H),

K. Asahi, H. Nishino / Tetrahedron 64 (2008) 1620e1634
1629
(C]O), 157.2 (C-9), 146.9, 144.8, 137.5 (3C, arom. C),
4.3.23. 8,11-Diphenyl-7,12-dioxatricyclo[4.3.3.01,6]dodec-
8-en-2-one (8hb)
130.0, 129.5, 128.8, 128.2, 128.0, 127.8, 127.5, 126.7, 126.0,
125.4, 125.3, 125.2 (15C, arom. CH), 117.3 (C-7), 99.9
(C-10), 89.2 (C-12), 73.0 (C-1), 43.9 (C-11), 40.0, 37.4, 26.8,
23.5 (4C, C-3, C-4, C-5, C-6). Anal. Calcd for C29H26O3:
C, 82.44; H, 6.20. Found: C, 82.44; H, 6.27. FAB HRMS
(acetoneeNBA) calcd for C29H27O3 423.1960 (Mþ1). Found
423.1958.
Rf¼0.47 (chloroform); colorless oil; IR (KBr) n 1705
1
(C]O); H NMR (300 MHz, CDCl3) d 7.67e7.64 (2H, m,
arom. H), 7.50e7.26 (8H, m, arom. H), 5.28 (1H, s, H-9),
5.15 (1H, dd, J¼11.4, 4.4 Hz, H-9), 2.66e2.37 (3H, m,
CH2), 2.54 (1H, dd, J¼12.8, 4.4 Hz, H-10), 2.19 (1H, dd,
J¼12.8, 11.4 Hz, H-10), 2.11e1.94 (3H, m, CH2); 13C NMR
(75 MHz, CDCl3) d 209.5 (C]O), 159.0 (C-8), 139.0
(arom. C), 129.5 (2C, arom. CH), 129.3 (arom. C), 128.5,
128.0, 126.1, 125.6 (8C, arom. CH), 117.9 (C-6), 96.6 (C-9),
79.5 (C-11), 68.8 (C-1), 44.2 (C-10), 37.1 (C-5), 33.4 (C-3),
17.5 (C-4). FAB HRMS (acetoneeNBA) calcd for C22H20O3
332.1412 (M). Found 332.1414.
4.3.20. 10,13,13-Triphenyl-9,14-dioxatricyclo[6.3.3.01,8]-
tetradec-10-en-2-one (8ae)
Rf¼0.78 (chloroform); colorless oil; IR (KBr) n 1697
1
(C]O); H NMR (300 MHz, CDCl3) d 7.46e7.44 (2H, m,
arom. H), 7.35e7.32 (2H, m, arom. H), 7.26e7.12 (11H,
m, arom. H), 7.00e6.95 (2H, m, arom. H), 6.85e6.80 (1H,
m, arom. H), 4.96 (1H, s, H-11), 3.39 (1H, d, J¼13.2 Hz,
H-12), 3.04 (1H, d, J¼13.2 Hz, H-12), 2.88 (1H, ddd,
J¼12.1, 6.4, 4.7 Hz, H-7), 2.57 (1H, ddd, J¼15.8, 6.4,
2.6 Hz, H-3), 2.27 (1H, ddd, J¼12.1, 10.6, 5.5 Hz, H-7),
1.97 (1H, ddd, J¼15.8, 10.4, 3.3 Hz, H-3), 1.84e1.58 (5H,
m, H-4, H-5, H-6), 1.27e1.20 (1H, m, CH2); 13C NMR
(75 MHz, CDCl3) d 212.1 (C]O), 157.1 (C-10), 147.0,
144.7, 129.7 (3C, arom. C), 128.8, 128.1, 127.8, 127.5,
126.7, 126.1, 125.7, 125.4, 125.3 (15C, arom. CH), 120.6
(C-8), 99.1 (C-11), 88.3 (C-13), 71.2 (C-1), 42.2, 35.8,
26.3, 24.7, 24.2 (5C, C-3, C-4, C-5, C-6, C-7). FAB HRMS
(acetoneeNBA) calcd for C30H29O3 437.2117 (Mþ1). Found
437.2119.
4.3.24. Methyl 8-(benzyl-tert-butoxycarbonylamino)-2-oxo-
11-phenyl-7,12-dioxatricyclo[4.3.3.01,6]dodec-10-ene-8-
carboxylate (8ib) (stereoisomer 1)
Rf¼0.44 (diethyl etherehexane, 1:1, v/v); colorless oil; IR
(KBr) n 1755, 1709 (C]O); 1H NMR (300 MHz, CDCl3)
d 7.57e7.51 (2H, m, arom. H), 7.40e7.18 (8H, m, arom. H),
5.17 (1H, s, H-10), 4.87 (1H, d, J¼16.5 Hz, PheCH2), 4.55
(1H, d, J¼16.5 Hz, PheCH2), 3.51 (1H, s, CO2CH3), 3.44
(1H, d, J¼14.3 Hz, H-9), 2.71 (1H, d, J¼14.3 Hz, H-9),
2.45e2.39 (1H, m, CH2), 2.19e2.15 (1H, m, CH2), 2.06e
1.94 (1H, m, CH2), 1.74e1.58 (1H, m, CH2), 1.42 (10H, s,
C(CH3)3, CH2), 1.04e0.96 (1H, m, CH2); 13C NMR
(75 MHz, CDCl3) d 207.9 (C]O), 169.7 (C]O), 157.5,
154.4 (2C, C]O, C-11), 140.1 (arom. C), 129.4 (arom. CH),
129.2 (arom. C), 128.4, 128.3, 126.6, 125.5 (9C, arom. CH),
119.0 (C-6), 98.4 (C-10), 95.3 (C-8), 81.8 (C(CH3)3), 67.6
(C-1), 52.8 (CO2CH3), 47.8 (C-9), 45.2 (PheCH2), 36.6
(C-5), 32.7 (C-3), 28.2 (C(CH3)3), 17.0 (C-4). FAB HRMS (ace-
toneeNBA) calcd for C30H33NO7 519.2257 (M). Found
519.2238.
4.3.21. 11-Methyl-8,11-diphenyl-7,12-dioxatricyclo-
[4.3.3.01,6]dodec-8-en-2-one (8gb) (stereoisomer 1)
Rf¼0.56 (chloroform); colorless oil; IR (KBr) n 1705
1
(C]O); H NMR (300 MHz, CDCl3) d 7.70e7.19 (10H, m,
arom. H), 5.39 (1H, s, H-9), 2.89 (1H, d, J¼14.3 Hz, H-10),
2.67e2.23 (3H, m, CH2), 2.08 (1H, d, J¼14.3 Hz, H-10),
1.99e1.86 (3H, m, CH2), 1.63 (3H, s, CH3); 13C NMR
(75 MHz, CDCl3) d 209.0 (C]O), 157.5 (C-8), 147.9, 129.6
(2C, arom. C), 129.4, 128.5, 128.2, 126.7, 125.6, 124.1
(10C, arom. CH), 119.2 (C-6), 98.8 (C-9), 86.3 (C-11), 69.1
(C-1), 47.2 (C-10), 36.7 (C-5), 34.0 (C-3), 30.3 (CH3), 17.3
(C-4). FAB HRMS (acetoneeNBA) calcd for C23H23O3
347.1647 (Mþ1). Found 347.1551.
4.3.25. Methyl 8-(benzyl-tert-butoxycarbonylamino)-2-oxo-
11-phenyl-7,12-dioxatricyclo[4.3.3.01,6]dodec-10-ene-8-
carboxylate (8ib) (stereoisomer 2)
Rf¼0.33 (diethyl etherehexane, 1:1, v/v); colorless prisms
(from diethyl etherehexane); mp 140.0 ꢁC; IR (KBr) n
1
174.7, 1711 (C]O); H NMR (300 MHz, CDCl3) d 7.54e
7.51 (2H, m, arom. H), 7.35e7.33 (3H, m, arom. H), 7.27e
7.25 (2H, m, arom. H), 7.11e7.03 (3H, m, arom. H), 5.37
(1H, s, H-10), 4.47 (1H, d, J¼16.2 Hz, PheCH2), 4.44 (1H,
d, J¼16.2 Hz, PheCH2), 3.66 (1H, s, CO2CH3), 3.60 (1H, d,
J¼14.7 Hz, H-9), 2.69 (1H, d, J¼14.7 Hz, H-9), 2.52e2.36
(3H, m, CH2), 2.07e2.00 (1H, m, CH2), 1.88e1.77 (2H, m,
CH2), 1.36 (9H, s, C(CH3)3); 13C NMR (75 MHz, CDCl3)
d 207.6 (C]O), 170.4 (C]O), 156.0, 154.6 (2C, C]O,
C-11), 139.1 (arom. C), 129.5 (arom. CH), 129.1 (arom. C),
128.4, 127.7, 126.4, 125.5 (9C, arom. CH), 120.7 (C-6),
99.7 (C-10), 95.0 (C-8), 81.4 (C(CH3)3), 66.9 (C-1), 52.7
(CO2CH3), 46.7 (2C, C-9, PheCH2), 36.8 (C-5), 33.0 (C-3),
28.1 (C(CH3)3), 17.4 (C-4). Anal. Calcd for C30H33NO7:
C, 69.35; H, 6.40; N, 2.70. Found: C, 69.26; H, 6.46;
N, 2.67.
4.3.22. 11-Methyl-8,11-diphenyl-7,12-dioxatricyclo[4.3.3.01,6]-
dodec-8-en-2-one (8gb) (stereoisomer 2)
Rf¼0.39 (chloroform); colorless oil; IR (KBr) n 1707
1
(C]O); H NMR (300 MHz, CDCl3) d 7.43e6.87 (10H, m,
arom. H), 4.78 (1H, s, H-9), 2.94 (1H, d, J¼13.2 Hz, H-10),
2.61e2.34 (3H, m, CH2), 2.39 (1H, d, J¼13.2 Hz, H-10),
1.99e1.86 (3H, m, CH2), 1.56 (3H, s, CH3); 13C NMR
(75 MHz, CDCl3) d 209.7 (C]O), 157.2 (C-8), 146.0, 129.5
(2C, arom. C), 128.8, 127.8, 127.5, 126.1, 125.3, 124.5
(10C, arom. CH), 118.1 (C-6), 97.1 (C-9), 86.6 (C-11), 69.0
(C-1), 46.4 (C-10), 36.7 (C-5), 34.0 (C-3), 32.6 (CH3), 17.4
(C-4). FAB HRMS (acetoneeNBA) calcd for C23H23O3
347.1647 (Mþ1). Found 347.1553.

1630
K. Asahi, H. Nishino / Tetrahedron 64 (2008) 1620e1634
4.3.26. 3,3-Dimethyl-8,11,11-triphenyl-7,12-dioxatricyclo-
[4.3.3.01,6]dodec-8-en-2-one (8af)
127.5, 126.1, 125.2 (15C, arom. CH), 94.3 (C-9), 81.4 (C-12),
66.3 (C-1), 39.2 (C-13), 35.4, 26.3, 26.0 (5C, C-3, C-4, C-5,
C-6, C-7). Anal. Calcd for C30H28O3: C, 82.54; H, 6.46. Found:
C, 82.48; H, 6.59.
Rf¼0.31 (chloroformehexane, 5:5, v/v); colorless needles
(from chloroformediethyl ether); mp 199e200 ꢁC; IR (KBr)
1
n 1697 (C]O); H NMR (300 MHz, CDCl3) d 7.60e6.83
(15H, m, arom. H), 4.88 (1H, s, H-9), 3.36 (1H, d,
J¼13.2 Hz, H-10), 2.77 (1H, d, J¼13.2 Hz, H-10), 2.53 (1H,
ddd, J¼14.0, 5.9, 2.2 Hz, H-5), 2.04 (1H, ddd, J¼14.0, 12.3,
2.6 Hz, H-5), 1.82 (1H, ddd, J¼14.1, 12.3, 2.2 Hz, H-4), 1.66
(1H, ddd, J¼14.1, 5.9, 2.6 Hz, H-4), 1.14 (3H, s, CH3), 1.09
(3H, s, CH3); 13C NMR (75 MHz, CDCl3) d 214.3 (C]O),
157.1 (C-8), 146.2, 144.4, 129.4 (3C, arom. C), 128.9, 128.2,
127.8, 127.5, 126.9, 126.3, 125.7, 125.4 (15C, arom. CH),
118.2 (C-6), 98.1 (C-9), 89.3 (C-11), 68.6 (C-1), 46.9 (C-10),
42.9 (C-3), 32.5 (C-5), 30.9 (C-4), 28.7, 26.6 (2C, CH3ꢂ2).
Anal. Calcd for C30H28O3: C, 82.54; H, 6.46. Found: C,
82.46; H, 6.37.
4.3.30. 11,11-Diphenyl-7,12-dioxatricyclo[4.3.3.01,6]-
dodecane-2,8-dione (10)
Rf¼0.36 (chloroformemethanol, 98:2, v/v); colorless nee-
dles (from chloroformediethyl ether); mp 164.0 ꢁC; IR (KBr)
1
n 1786, 1715 (C]O); H NMR (300 MHz, CDCl3) d 7.49e
7.18 (10H, m, arom. H), 3.29 (1H, d, J¼13.6 Hz, H-10), 2.94
(1H, d, J¼18.7 Hz, H-9), 2.88 (1H, d, J¼13.6 Hz, H-10),
2.61e2.54 (1H, m, CH2), 2.45e2.38 (2H, m, CH2), 2.43 (1H,
d, J¼18.7 Hz, H-9), 1.99e1.89 (1H, m, CH2), 1.85e1.68 (2H,
m, CH2); 13C NMR (75 MHz, CDCl3) d 206.8, 171.7 (2C,
C]O), 144.2, 144.0 (2C, arom. C), 128.5, 128.3, 127.6,
127.4, 125.4, 125.2 (10C, arom. CH), 117.3 (C-6), 90.7 (C-11),
60.9 (C-1), 46.6, 37.9, 36.2, 33.0, 17.0 (5C, CH2). Anal. Calcd
for C22H20O4: C, 75.84; H, 5.79. Found: C, 75.91; H, 5.59.
4.3.27. 5,5-Dimethyl-8,11,11-triphenyl-7,12-dioxatricyclo-
[4.3.3.01,6]dodec-8-en-2-one (8af0)
Rf¼0.20 (chloroformehexane, 5:5, v/v); colorless prisms
1
(C]O); H NMR (300 MHz, CDCl3) d 7.54e6.76 (15H, m,
4.3.31. Ethyl 3-(4-oxo-2,2-diphenyl-2,3,5,6-tetrahydro-4H-
benzofuran-3a-yl)acetate (11)
(from diethyl etherehexane); mp 173 ꢁC; IR (KBr) n 1701
Rf¼0.49 (chloroformemethanol, 98:2, v/v); colorless oil; IR
(KBr) n 1734, 1719 (C]O); 1H NMR (300 MHz, CDCl3)
d 7.56e7.53 (2H, m, arom. H), 7.38e7.17 (8H, m, arom. H),
5.25 (1H, dd, J¼9.2, 2.2 Hz, H-7), 4.02 (2H, q, J¼7.0 Hz,
OeCH2CH3), 3.25 (1H, d, J¼13.6 Hz, H-3), 2.97 (1H, d,
J¼13.6 Hz, H-3), 2.73e2.59 (2H, m, CH2), 2.58 (1H, d,
J¼14.3 Hz, CH2eCO2Et), 2.44e2.31 (2H, m, CH2), 2.26
(1H, d, J¼14.3 Hz, CH2eCO2Et), 1.18 (3H, t, J¼7.0 Hz,
OeCH2CH3); 13C NMR (75 MHz, CDCl3) d 208.7, 169.5
(2C, C]O), 156.0 (C-7a), 145.9, 144.9 (2C, arom. C), 128.5,
128.3, 127.3, 127.2, 125.34, 125.32 (10C, arom. CH), 94.2
(C-7), 89.6 (C-2), 60.9 (OeCH2CH3), 55.5 (C-3a), 41.8, 39.0,
34.2, 20.0 (4C, CH2), 14.0 (OeCH2CH3). FAB HRMS
(acetoneeNBA) calcd for C24H25O4 377.1753 (Mþ1). Found
377.1753.
arom. H), 4.74 (1H, s, H-9), 3.45 (1H, d, J¼13.2 Hz, H-10),
2.64 (1H, d, J¼13.2 Hz, H-10), 2.54 (1H, ddd, J¼19.5, 8.6,
2.6 Hz, H-3), 2.38 (1H, ddd, J¼19.5, 9.5, 8.6 Hz, H-3), 1.97
(1H, ddd, J¼14.1, 9.5, 8.6 Hz, H-4), 1.58 (1H, ddd, J¼14.1,
8.6, 2.6 Hz, H-4), 1.39 (3H, s, CH3), 0.99 (3H, s, CH3); 13C
NMR (75 MHz, CDCl3) d 210.2 (C]O), 157.7 (C-8), 146.8,
144.6, 129.4 (3C, arom. C), 128.9, 128.2, 127.7, 127.4, 126.6,
126.1, 125.4, 125.3, 124.9 (15C, arom. CH), 121.0 (C-6), 96.6
(C-9), 88.8 (C-11), 68.2 (C-1), 46.7 (C-10), 37.8 (C-5), 33.6
(C-3), 31.0 (C-4), 23.1, 22.2 (2C, CH3ꢂ2). Anal. Calcd for
C30H28O3: C, 82.54; H, 6.46. Found: C, 82.80; H, 6.34.
4.3.28. 9,11,11-Triphenyl-10-oxaspiro[6.5]dodec-9-ene-
2,7-dione (9ad)
Rf¼0.53 (chloroform); colorless oil; IR (KBr) n 1701
1
(C]O); H NMR (300 MHz, CDCl3) d 7.82e7.78 (2H, m,
4.3.32. 3,8,8-Triphenyl-2,9-dioxatricyclo[4.3.3.01,6]dodec-
3-en-12-one (13aa)
arom. H), 7.45e7.12 (13H, m, arom. H), 5.37 (1H, s, H-8),
3.35 (2H, s, H-12), 2.52e2.46 (2H, m, H-3, H-6), 2.38e2.32
(2H, m, H-3, H-6), 1.92e1.78 (4H, m, H-4, H-5); 13C NMR
(75 MHz, CDCl3) d 208.8 (2C, C]O), 152.2 (C-9), 143.6,
134.5 (3C, arom. C), 129.0, 128.4, 128.3, 127.6, 125.9, 125.2
(15C, arom. CH), 93.9 (C-8), 81.2 (C-11), 65.1 (C-1), 40.1, 35.5,
28.6 (5C, C-3, C-4, C-5, C-6, C-12). FAB HRMS (acetonee
NBA) calcd for C29H26O3 422.1882 (M). Found 422.1877.
Rf¼0.71 (chloroform); colorless prisms (from chloroforme
hexane); mp 155e156 ꢁC; IR (KBr) n 1749 (C]O); 1H NMR
(300 MHz, CDCl3) d 7.43e7.07 (15H, m, arom. H), 5.29 (1H,
dd, J¼6.1, 2.6 Hz, H-4), 3.36 (1H, d, J¼13.2 Hz, H-7), 2.73
(1H, d, J¼13.2 Hz, H-7), 2.59 (1H, d, J¼14.7 Hz, H-11),
2.43e2.12 (5H, m, H-5, H-10, H-11); 13C NMR (75 MHz,
CDCl3) d 216.7 (C]O), 150.1 (C-3), 147.2, 144.8, 134.7
(3C, arom. C), 130.0, 128.2, 128.1, 128.0, 127.9, 127.2,
126.6, 125.7, 125.57, 125.55, 124.69, 124.67 (15C, arom.
CH), 112.6 (C-1), 92.5 (C-4), 89.7 (C-8), 56.0 (C-6), 45.2
(C-7), 35.2 (C-10), 30.2 (C-11), 23.8 (C-5). Anal. Calcd for
C28H24O3: C, 82.33; H, 5.92. Found: C, 82.31; H, 6.06.
4.3.29. 10,12,12-Triphenyl-11-oxaspiro[7.5]tridec-10-ene-
2,8-dione (9ae)
Rf¼0.67 (chloroform); colorless needles (from chloroforme
hexane); mp 192e193 ꢁC; IR (KBr) n 1693 (C]O); 1H NMR
(300 MHz, CDCl3) d 7.84e7.81 (2H, m, arom. H), 7.41e7.19
(13H, m, arom. H), 5.60 (1H, s, H-9), 3.34 (2H, s, H-13),
2.43e2.37 (4H, m, H-3, H-7), 1.68e1.47 (6H, m, H-4, H-5,
H-6); 13C NMR (75 MHz, CDCl3) d 207.0 (2C, C]O), 152.1
(C-10), 143.6, 134.6 (3C, arom. C), 129.0, 128.4, 128.2,
4.3.33. 3,12,12-Triphenyl-2,11-dioxatricyclo[4.4.3.01,6]-
tridec-3-en-7-one (13ab)
Rf¼0.62 (chloroform); colorless microcrystals (from ethyl
acetateehexane); mp 169e170 ꢁC; IR (KBr) n 1711 (C]O);

K. Asahi, H. Nishino / Tetrahedron 64 (2008) 1620e1634
1631
1H NMR (300 MHz, CDCl3) d 7.51e7.47 (4H, m, arom. H),
7.28e7.06 (11H, m, arom. H), 5.13 (1H, dd, J¼5.3, 2.8 Hz,
H-4), 3.79 (1H, d, J¼12.5 Hz, H-13), 2.74 (1H, d,
J¼12.5 Hz, H-13), 2.54e1.85 (8H, m, H-5, H-8, H-9, H-10);
13C NMR (75 MHz, CDCl3) d 208.9 (C]O), 149.4 (C-3),
148.8, 145.8, 135.1 (3C, arom. C), 128.0, 127.90, 127.87,
126.6, 126.2, 125.3, 125.2, 124.4 (15C, arom. CH), 107.9
(C-1), 90.62, 90.60 (1C, C-4), 87.3 (C-12), 57.9 (C-6), 42.5
(C-13), 36.3 (C-10), 29.6 (C-8), 27.3 (C-5), 19.3 (C-9).
Anal. Calcd for C29H26O3: C, 82.44; H, 6.20. Found: C,
82.14; H, 6.23.
(C-1), 88.2 (C-3), 61.6 (C-5), 46.2 (C-4), 36.5, 33.5, 31.5,
25.2 (4C, C-7, C-8, BzeCH2CH2). FAB HRMS (acetonee
NBA) calcd for C28H26O4 426.1831 (M). Found 426.1805.
4.3.37. 1-Acetoxy-5-(3-oxo-3-phenylpropyl)-3,3-diphenyl-2-
oxabicyclo[3.3.0]octan-6-one (14aa0)
Rf¼0.29 (chloroform); colorless oil; IR (KBr) n 1746, 1688
(C]O), 1236 (Ac); 1H NMR (300 MHz, CDCl3) d 7.96e7.92
(2H, m, arom. H), 7.56e7.08 (13H, m, arom. H), 3.52e3.46
(1H, m, CH2), 3.35 (1H, d, J¼12.7 Hz, H-4), 3.24e3.13
(1H, m, BzeCH2CH2), 3.04e2.93 (1H, m, BzeCH2CH2),
2.83 (1H, d, J¼12.7 Hz, H-4), 2.58e1.93 (5H, m, H-7, H-8,
BzeCH2CH2), 1.68 (3H, s, Ac); 13C NMR (75 MHz,
CDCl3) d 215.7, 198.9, 169.4 (3C, C]O), 147.7, 145.5,
136.5 (3C, arom. C), 133.2, 128.6, 128.3, 128.19, 128.17,
127.99, 127.96, 127.9, 126.94, 126.90, 126.7, 124.9, 124.8
(15C, arom. CH), 114.3 (C-1), 90.0 (C-3), 63.3 (C-5), 45.3
(C-4), 36.0, 33.3, 29.4, 24.5 (4C, C-7, C-8, BzeCH2CH2),
21.4 (Ac). FAB MS m/z (rel intensity), 468 (3, M), 409 (70),
391 (48), 277 (84), 154 (28), 105 (100), 77 (18), 43 (9).
4.3.34. 9,9-Dimethyl-3,12,12-triphenyl-2,11-dioxatricyclo-
[4.4.3.01,6]tridec-3-en-7-one (13ac)
Rf¼0.73 (chloroform); colorless prisms (from chloroform);
mp 204e206 ꢁC; IR (KBr) n 1709 (C]O); 1H NMR
(300 MHz, CDCl3) d 7.57e7.00 (15H, m, arom. H), 5.11 (1H,
dd, J¼5.3, 2.8 Hz, H-4), 4.05 (1H, d, J¼12.8 Hz, H-13), 2.63
(1H, d, J¼12.8 Hz, H-13), 2.57 (1H, d, J¼14.5 Hz, H-10),
2.50 (1H, dd, J¼18.4, 2.8 Hz, H-5), 2.37 (1H, dd, J¼14.5,
1.8 Hz, H-8), 2.27 (1H, dd, J¼18.4, 5.3 Hz, H-5), 2.08 (1H,
dd, J¼14.5, 1.8 Hz, H-8), 2.03 (1H, d, J¼14.5 Hz, H-10),
1.05 (3H, s, CH3), 1.00 (3H, s, CH3); 13C NMR (75 MHz,
CDCl3) d 208.9 (C]O), 150.1 (C-3), 149.3, 135.1, 132.4
(3C, arom. C), 128.2, 128.1, 127.9, 127.83, 127.78, 126.5,
125.8, 125.5, 124.6, 124.4 (15C, arom. CH), 108.1 (C-1),
90.59, 90.55 (1C, C-4), 87.6 (C-12), 57.0 (C-6), 49.3 (C-10),
42.1 (C-8), 41.2 (C-13), 33.1 (CH3), 32.4 (C-9), 27.8 (CH3),
27.7 (C-5). Anal. Calcd for C31H30O3: C, 82.64; H, 6.71. Found:
C, 82.36; H, 6.81.
4.3.38. 6-Hydroxy-1-(3-oxo-3-phenylpropyl)-8,8-diphenyl-
7-oxabicyclo[4.3.0]nonan-2-one (14ab)
Rf¼0.40 (chloroformemethanol, 98:2, v/v); colorless micro-
crystals (from ethyl acetateehexane); mp 96e98 ꢁC; IR (KBr)
n 3600e3100 (OH), 1714, 1684 (C]O); 1H NMR (300 MHz,
CDCl3) d 7.92e7.90 (2H, m, arom. H), 7.56e7.08 (14H, m,
OH, arom. H), 3.84 (1H, d, J¼12.1 Hz, H-9), 2.99e2.89 (1H,
m, BzeCH2CH2), 2.83e2.75 (1H, m, BzeCH2CH2), 2.71
(1H, d, J¼12.1 Hz, H-9), 2.48e1.83 (8H, m, H-3, H-4, H-5,
BzeCH2CH2); 13C NMR (75 MHz, CDCl3) d 209.3, 199.0
(2C, C]O), 149.7, 146.4, 136.6 (3C, arom. C), 133.1, 128.5,
128.2, 128.0, 127.9, 126.5, 126.3, 125.0, 124.8 (15C, arom.
CH), 107.1 (C-6), 86.1 (C-8), 63.8 (C-1), 43.2 (C-9), 37.5,
34.3, 32.6 (3C, C-3, C-5, BzeCH2CH2), 26.6 (BzeCH2CH2),
19.3 (C-4). Anal. Calcd for C29H28O4$2/5H2O: C, 77.82; H,
6.44. Found: C, 77.87; H, 6.46.
4.3.35. 2,3,4,4a,5,6,7,8,9,9a-Decahydro-4a,9a-(12,12-
diphenylepoxyethano)xanthen-1-one (13ad)
Rf¼0.51 (chloroform); colorless microcrystals (from chloro-
1
formehexane); mp 152.5 ꢁC; IR (KBr) n 1709 (C]O); H
NMR (300 MHz, CDCl3) d 7.46e7.42 (4H, m, arom. H),
7.25e7.08 (6H, m, arom. H), 3.73 (1H, d, J¼12.5 Hz, H-13),
2.64 (1H, d, J¼12.5 Hz, H-13), 2.49e2.33 (2H, m, CH2),
2.15e1.83 (9H, m, CH2), 1.63e1.45 (5H, m, CH2); 13C NMR
(75 MHz, CDCl3) d 209.2 (C]O), 148.6, 145.8, 144.2 (3C,
C-10a, arom. C), 127.7, 126.5, 126.1, 125.4, 125.3 (10C,
arom. CH), 106.8 (C-4a), 98.1 (C-8a), 87.0 (C-12), 58.7
(C-9a), 42.8, 36.4, 31.8, 29.8, 27.8, 26.7, 22.7, 19.1 (9C,
CH2). Anal. Calcd for C27H28O3: C, 80.97; H, 7.05. Found:
C, 80.93; H, 6.97.
4.3.39. 6-Hydroxy-4,4-dimethyl-1-(3-oxo-3-phenylpropyl)-
8,8-diphenyl-7-oxabicyclo[4.3.0]nonan-2-one (14ac)
Rf¼0.42 (chloroformemethanol, 98:2, v/v); colorless micro-
crystals (from ethyl acetate); mp 138e139 ꢁC; IR (KBr) n
1
3600e3100 (OH), 1707, 1684 (C]O); H NMR (300 MHz,
CDCl3) d 7.93e7.90 (2H, m, arom. H), 7.57e7.05 (14H, m,
OH, arom. H), 4.12 (1H, d, J¼12.5 Hz, H-9), 3.02e2.91 (1H,
m, BzeCH2CH2), 2.76e2.65 (1H, m, BzeCH2CH2), 2.57
(1H, d, J¼12.5 Hz, H-9), 2.51 (1H, d, J¼13.8 Hz, H-5),
2.33e1.98 (5H, m, H-3, H-5, BzeCH2CH2), 1.07 (3H, s,
CH3), 0.93 (3H, s, CH3); 13C NMR (75 MHz, CDCl3)
d 209.4, 198.9 (2C, C]O), 151.2, 146.0, 136.6 (3C, arom.
C), 133.2, 128.6, 128.3, 128.0, 127.9, 126.4, 126.3, 125.2,
124.3 (15C, arom. CH), 107.8 (C-6), 86.8 (C-8), 63.5 (C-1),
50.2 (C-5), 45.0 (C-3), 41.5 (C-9), 34.4 (BzeCH2CH2), 33.3
(CH3), 32.1 (C-4), 28.0 (BzeCH2CH2), 27.2 (CH3). Anal.
Calcd for C31H32O4: C, 79.46; H, 6.88. Found: C, 79.26; H,
6.84.
4.3.36. 1-Hydroxy-5-(3-oxo-3-phenylpropyl)-3,3-diphenyl-
2-oxabicyclo[3.3.0]octan-6-one (14aa)
Rf¼0.18 (chloroform); colorless oil; IR (KBr) n 3600e3100
(OH), 1736, 1684 (C]O); 1H NMR (300 MHz, CDCl3)
d 7.92e7.89 (2H, m, arom. H), 7.54e7.08 (13H, m, arom. H),
3.60 (1H, br s, OH), 3.39 (1H, d, J¼12.8 Hz, H-4), 3.24e3.13
(1H, m, BzeCH2CH2), 2.98e2.87 (1H, m, BzeCH2CH2),
2.68 (1H, d, J¼12.8 Hz, H-4), 2.63e1.87 (6H, m, H-7, H-8,
BzeCH2CH2); 13C NMR (75 MHz, CDCl3) d 218.8, 199.5
(2C, C]O), 148.3, 145.4, 136.5 (3C, arom. C), 133.2, 128.5,
128.2, 128.1, 127.0, 126.8, 125.3 (15C, arom. CH), 112.4

1632
K. Asahi, H. Nishino / Tetrahedron 64 (2008) 1620e1634
4.3.40. Ethyl 6-hydroxy-8,8-diphenyl-7-
oxabicyclo[4.3.0]nonan-2-one-1-propionate (14ae)
145.4, 138.2, 134.3 (5C, arom. C, C-3), 130.6, 128.5, 128.1,
128.0, 127.9, 127.6, 126.6, 125.8, 125.3, 124.1, 123.4 (arom.
CH), 122.5 (arom. C), 114.6 (arom. CH), 102.7 (C-1), 92.9,
92.8 (1C, C-4), 88.5 (C-12), 50.0 (C-6), 45.2 (C-13), 29.7
(NeCH3), 26.3 (C-5). Anal. Calcd for C33H27NO3: C, 81.63;
H, 5.60; N, 2.88. Found: C, 81.64; H, 5.73; N, 2.92.
Rf¼0.33 (chloroformemethanol, 98:2, v/v); colorless oil; IR
(KBr) n 3600e3200 (OH), 1732, 1713 (C]O); 1H NMR
(300 MHz, CDCl3) d 7.51e7.06 (10H, m, arom. H), 4.09 (2H,
q, J¼7.1 Hz, OeCH2CH3), 3.75 (1H, d, J¼12.1 Hz, H-9),
2.74 (1H, br s, OH), 2.63 (1H, d, J¼12.1 Hz, H-9), 2.42e1.80
(10H, m, CH2ꢂ5), 1.20 (3H, t, J¼7.1 Hz, OeCH2CH3); 13C
NMR (75 MHz, CDCl3) d 208.8, 172.9 (2C, C]O), 149.7,
146.2 (2C, arom. C), 128.0, 127.7, 126.3, 126.2, 124.9, 124.7
(10C, arom. CH), 106.9 (C-6), 86.0 (C-8), 63.6 (C-1), 60.4
(OeCH2CH3), 42.9, 37.5, 32.4, 30.2, 27.6, 19.2 (6C, CH2),
14.0 (OeCH2CH3). FAB HRMS (acetoneeNBA) calcd for
C25H28O5 408.1937 (M). Found 408.1938.
4.3.44. 3,12,12-Triphenyl-2,8,11-trioxa-9,10-benzotricyclo-
[4.4.3.01,6]tridec-3-en-7-one (17ac)
Rf¼0.67 (chloroform); colorless microcrystals (from diethyl
etherehexane); mp 159 ꢁC; IR (KBr) n 1769 (C]O); 1H NMR
(300 MHz, CDCl3) d 7.73e7.04 (19H, m, arom. H), 5.18 (1H,
dd, J¼5.3, 2.6 Hz, H-4), 3.80 (1H, d, J¼12.7 Hz, H-13), 3.21
(1H, d, J¼12.7 Hz, H-13), 2.60 (1H, dd, J¼18.5, 5.3 Hz,
H-5), 2.36 (1H, dd, J¼18.5, 2.6 Hz, H-5); 13C NMR
(75 MHz, CDCl3) d 169.4 (C]O), 149.6, 148.3, 147.5, 145.0,
134.0 (5C, arom. C, C-3), 131.5, 128.3, 128.2, 128.1, 128.0,
127.0, 126.7, 125.6, 125.2, 125.0, 124.2 (arom. CH), 120.5
(arom. C), 116.9 (arom. CH), 101.6 (C-1), 92.0, 91.9 (1C, C-4),
88.8 (C-12), 50.6 (C-6), 44.4 (C-13), 26.3 (C-5). Anal. Calcd
for C32H24O4: C, 81.34; H, 5.12. Found: C, 81.37; H, 5.17.
4.3.41. Ethyl 3-(4-oxo-2,2-diphenyl-2,3,5,6-tetrahydro-4H-
benzofuran-3a-yl)propionate (15)
Rf¼0.66 (chloroformemethanol, 98:2, v/v); colorless oil; IR
1
(KBr) n 1734, 1713 (C]O); H NMR (300 MHz, CDCl3)
d 7.50e7.17 (10H, m, arom. H), 5.26 (1H, dd, J¼7.0, 2.2 Hz,
H-7), 4.01 (2H, q, J¼7.0 Hz, OeCH2CH3), 2.98 (1H, d,
J¼13.6 Hz, H-3), 2.84 (1H, d, J¼13.6 Hz, H-3), 2.39e1.95
(8H, m, CH2ꢂ4), 1.17 (3H, t, J¼7.0 Hz, OeCH2CH3); 13C
NMR (75 MHz, CDCl3) d 211.2, 172.3 (2C, C]O), 156.9
(C-7a), 145.6, 145.3 (2C, arom. C), 128.5, 128.3, 127.19,
127.17, 125.5, 125.0 (10C, arom. CH), 93.8 (C-7), 89.3 (C-2),
60.5 (OeCH2CH3), 57.2 (C-3a), 41.8, 34.8, 29.5, 28.3, 19.5
(5C, CH2), 14.1 (OeCH2CH3). FAB HRMS (acetoneeNBA)
calcd for C25H27O4 391.1909 (Mþ1). Found 391.1989.
4.3.45. 3-Methyl-8,11,11-triphenyl-2-aza-8,9-dioxa-3,4-
benzotricyclo[4.3.3.01,6]dodec-7-en-5-one (18)
Rf¼0.38 (chloroform); colorless microcrystals (from diethyl
etherehexane); mp 237e238 ꢁC; IR (KBr) n 1678 (C]O); 1H
NMR (300 MHz, CDCl3) d 7.93e7.11 (19H, m, arom. H), 5.61
(1H, s, H-7), 3.35 (3H, s, NeCH3), 3.21 (1H, d, J¼14.0 Hz,
H-12), 3.03 (1H, d, J¼14.0 Hz, H-12); 13C NMR (75 MHz,
CDCl3) d 171.9 (C]O), 152.5 (C-8), 144.1, 142.3, 142.1
(3C, arom. C), 135.0 (arom. CH), 134.9 (arom. C), 131.1,
128.8, 128.7, 128.6, 128.5, 128.4, 128.3, 128.2, 127.6, 127.5,
126.1, 125.9, 125.2, 123.1 (17C, arom. CH), 122.0 (arom. C),
114.7 (C-1), 114.5 (arom. CH), 94.2 (C-9), 81.2 (C-11), 57.6
(C-6), 40.6 (C-12), 30.6 (NeCH3). Anal. Calcd for
C32H25NO3: C, 81.51; H, 5.34; N, 2.97. Found: C, 81.50; H,
5.37; N, 2.95. FAB HRMS (acetoneeNBA) calcd for
C32H26NO3 472.1913 (Mþ1). Found 472.1917.
4.3.42. 3-Methyl-8,11,11-triphenyl-3-aza-7,12-dioxa-4,5-
benzotricyclo[4.3.3.01,6]dodec-8-en-2-one (17aa)
Rf¼0.58 (chloroform); colorless microcrystals (from diethyl
1
etherehexane); mp 94e95 ꢁC; IR (KBr) n 1663 (C]O); H
NMR (300 MHz, CDCl3) d 8.10e8.07 (1H, m, arom. H),
7.59e7.56 (2H, m, arom. H), 7.39e6.93 (16H, m, arom. H),
5.34 (1H, s, H-9), 3.66 (1H, d, J¼13.0 Hz, H-10), 3.26 (3H, s,
NeCH3), 3.04 (1H, d, J¼13.0 Hz, H-10); 13C NMR (75 MHz,
CDCl3) d 168.8 (C]O), 155.1 (C-8), 145.4, 144.2, 136.1
(3C, arom. C), 130.2 (arom. CH), 129.3 (arom. C), 128.8,
128.0, 127.8, 127.7, 126.9, 126.5, 125.6, 125.4 (arom. CH),
123.8 (arom. C), 122.9, 114.3 (arom. CH), 112.4 (C-6), 98.70,
98.66 (1C, C-9), 89.2 (C-11), 62.8 (C-1), 50.4 (C-10), 29.3
(NeCH3). Anal. Calcd for C32H25NO3: C, 81.51; H, 5.34;
N, 2.97. Found: C, 81.48; H, 5.59; N, 2.82. FAB HRMS
(acetoneeNBA) calcd for C32H26NO3 472.1913 (Mþ1). Found
472.1910.
4.3.46. 3-(2-Hydroxy-2,2-diphenylethyl)-1-methyl-3-(2-oxo-
2-phenylethyl)-1H-quinoline-2,4-dione (19)
Rf¼0.27 (chloroform); colorless prisms (from ethyl acetatee
hexane); mp 180e183 ꢁC; IR (KBr) n 3600e3150 (OH), 1682,
1
1638 (C]O); H NMR (300 MHz, CDCl3) d 7.88e7.63 (3H,
m, arom. H), 7.60e7.01 (16H, m, arom. H), 4.41 (1H, d,
J¼17.8 Hz, BzeCH2), 4.10 (1H, d, J¼17.8 Hz, BzeCH2),
3.87 (1H, br s, OH), 3.08 (1H, d, J¼14.5 Hz, CH2), 3.00 (1H,
d, J¼14.5 Hz, CH2), 2.89 (3H, s, NeCH3); 13C NMR
(75 MHz, CDCl3) d 197.6, 196.3, 173.0 (3C, C]O), 146.1,
142.6 (2C, arom. C), 135.4 (2C, arom. C, arom. CH), 133.5,
128.4 (arom. CH), 128.3 (2C, arom. C, arom. CH), 127.94,
127.88, 126.8, 126.7, 125.4, 125.2, 122.8 (arom. CH), 120.9
(arom. C), 114.7 (arom. CH), 77.1 (Ph2pC), 54.8 (C-3), 51.0
(BzeCH2), 49.0 (CH2), 29.3 (NeCH3). Anal. Calcd for
C32H27NO4: C, 78.51; H, 5.56; N, 2.86. Found: C, 78.33; H,
5.64; N, 2.72. FAB HRMS (acetoneeNBA) calcd for
C32H27NO4 489.1940 (M). Found 489.1941.
4.3.43. 8-Methyl-3,12,12-triphenyl-8-aza-2,11-dioxa-9,10-
benzotricyclo[4.4.3.01,6]tridec-3-en-7-one (17ab)
Rf¼0.31 (chloroform); colorless prisms (from diethyl ethere
hexane); mp 209 ꢁC; IR (KBr) n 1672 (C]O); 1H NMR
(300 MHz, CDCl3) d 7.77e7.01 (19H, m, arom. H), 5.21 (1H,
dd, J¼5.3, 2.4 Hz, H-4), 3.78 (1H, d, J¼12.5 Hz, H-13), 3.14
(1H, d, J¼12.5 Hz, H-13), 3.07 (3H, s, NeCH3), 2.56 (1H,
dd, J¼18.5, 5.3 Hz, H-5), 2.15 (1H, dd, J¼18.5, 2.4 Hz, H-5);
13C NMR (75 MHz, CDCl3) d 170.6 (C]O), 147.8, 147.6,

K. Asahi, H. Nishino / Tetrahedron 64 (2008) 1620e1634
1633
4.3.47. 3-(2,2-Diphenylvinyl)-1-methyl-3-(2-oxo-2-phenyl-
ethyl)-1H-quinoline-2,4-dione (20aa)
acid (AlCl3 or EtAlCl2 in hexanes) (0.4 mmol) was added to the
reaction mixture, which was then stirred at room temperature.
The mixture was further heated under reflux until the starting
material was completely consumed as necessary. The resulting
solution was quenched with water (10 mL) and extracted with
chloroform (5 mLꢂ3). The combined chloroform extracts were
dried over anhydrous MgSO4 and concentrated to dryness under
vacuum. The obtained crude products were purified by column
chromatography on silica gel while eluting with chloroform,
giving the desired propellanes 13aa, 13ab, 13ac, and 17ab.
Rf¼0.49 (chloroform); colorless prisms (from hexane); mp
1
169 ꢁC; IR (KBr) n 1684, 1655 (C]O); H NMR (300 MHz,
CDCl3) d 7.93e7.83 (3H, m, arom. H), 7.58e7.50 (2H, m,
arom. H), 7.42e6.90 (14H, m, arom. H), 6.07 (1H, s,
Ph2pC]CH), 4.40 (1H, d, J¼17.6 Hz, BzeCH2), 4.28 (1H,
d, J¼17.6 Hz, BzeCH2), 3.02 (3H, s, NeCH3); 13C NMR
(75 MHz, CDCl3) d 197.4, 193.9, 171.0 (3C, C]O), 145.1
(Ph2pC), 143.1, 142.0, 137.3 (3C, arom. C), 135.5, 135.4
(arom. CH), 133.5 (arom. C), 129.7, 128.4, 128.3, 128.0,
127.8, 127.6, 127.5, 127.0, 126.2 (arom. CH), 126.2
(Ph2pC]CH), 122.5 (arom. CH), 120.7 (arom. C), 115.0
(arom. CH), 58.8 (C-3), 50.1 (BzeCH2), 29.5 (NeCH3).
Anal. Calcd for C32H25NO3: C, 81.51; H, 5.34; N, 2.97. Found:
C, 81.58; H, 5.36; N, 2.98. FAB HRMS (acetoneeNBA) calcd
for C32H26NO3 472.1913 (Mþ1). Found 472.1937.
Acknowledgements
This research was supported by Grants-in-Aid for Scientific
Research (C), No. 19550046, from Japan Society for the Pro-
motion of Science. We gratefully acknowledge Professor
Teruo Shinmyozu, Institute for Materials Chemistry and Engi-
neering, Kyushu University, Japan, for the measurement of the
high resolution FAB mass spectrum.
4.3.48. 3-(2,2-Diphenylvinyl)-1-methyl-3-(3-oxo-3-phenyl-
propyl)-1H-quinoline-2,4-dione (20ab)
Rf¼0.42 (chloroformemethanol, 98:2, v/v); colorless micro-
1
(KBr) n 1684, 1645 (C]O); H NMR (300 MHz, CDCl3)
Supplementary data
crystals (from ethyl acetateehexane); mp 139e140 ꢁC; IR
The result for the reaction of alkenes 1aee with 2aeh except
for the reaction of 1b,c with 2a without a 10-min heating after
finishing the oxidation (Scheme 1-1 and Table 1-1) (1 page),
and the experimental procedures (1 page), spectroscopic and
characterization data for 2 and the rest of the compounds de-
scribed in this paper (11 pages). The spectral data of dioxapro-
pellanes 3aa, 3ah, trioxapropellanes 4aa, 4ah, the by-product
acetates 5, 5ah, the bicycloacetate 6ah, and dioxapropellane
13ab produced by Lewis acid-induced cyclization (45 pages).
Supplementary data associated with this article can be found
in the online version, at doi:10.1016/j.tet.2007.12.017.
d 7.90e6.84 (19H, m, arom. H), 6.40 (1H, s, Ph2pC]CH),
3.08 (3H, s, NeCH3), 2.97e2.92 (2H, m, BzeCH2CH2),
2.75e2.69 (2H, m, BzeCH2CH2); 13C NMR (75 MHz,
CDCl3) d 198.3, 196.2, 172.0 (3C, C]O), 144.3, 142.7,
140.9, 138.3, 136.4 (5C, arom. C, Ph2pC), 135.9 (arom. CH),
133.0 (Ph2pC]CH), 130.7, 130.0, 128.5, 128.0, 127.6, 127.4,
127.1, 122.7 (arom. CH), 120.3 (arom. C), 114.6 (arom. CH),
59.8 (C-3), 35.8 (BzeCH2CH2), 33.3 (BzeCH2CH2), 29.3
(NeCH3). Anal. Calcd for C33H27NO3: C, 81.63; H, 5.60;
N, 2.88. Found: C, 81.93; H, 5.63; N, 2.92.
4.3.49. 9b-Hydroxy-5-methyl-3a-(3-oxo-3-phenylpropyl)-
2,2-diphenyl-3,3a,5,9b-tetrahydro-2H-furo[3,2-c]quinolin-
4-one (21)
References and notes
1. Pihko, A. J.; Koskinen, A. M. P. Tetrahedron 2005, 61, 8769e8807.
2. (a) Dugan, J. J.; de Mayo, P.; Nisbet, M.; Robinson, J. R.; Anchel, M.
J. Am. Chem. Soc. 1966, 88, 2838e2844; (b) Konishi, M.; Ohkuma, H.;
Tsuno, T.; Oki, T. J. Am. Chem. Soc. 1990, 112, 3715e3716.
3. Ellestad, G. A.; Kunstmann, M. P.; Whaley, H. A.; Patterson, E. L. J. Am.
Chem. Soc. 1968, 90, 1325e1332.
Rf¼0.33 (chloroformemethanol, 98:2, v/v); colorless prisms
(from ethyl acetate); mp 211e212 ꢁC; IR (KBr) n 3600e3100
(OH), 1680, 1641 (C]O); 1H NMR (300 MHz, CDCl3)
d 7.84e6.92 (19H, m, arom. H), 3.77 (1H, d, J¼11.7 Hz,
H-3), 3.76 (1H, br s, OH), 3.15 (1H, d, J¼11.7 Hz, H-3),
3.09e2.67 (2H, m, BzeCH2CH2), 2.94 (3H, s, NeCH3),
2.28e2.11 (2H, m, BzeCH2CH2); 13C NMR (75 MHz,
CDCl3) d 199.8, 170.3 (2C, C]O), 147.9, 145.6, 137.7, 136.1
(4C, arom. C), 133.0, 130.1, 128.3, 127.8, 127.6, 126.8, 126.4,
126.2, 125.5 (arom. CH), 125.2 (arom. C), 125.0, 123.3, 114.5
(arom. CH), 101.6 (C-9b), 87.4 (C-2), 57.8 (C-3a), 48.1 (C-3),
34.0 (BzeCH2CH2), 29.9 (NeCH3), 26.1 (BzeCH2CH2).
Anal. Calcd for C33H29NO4: C, 78.71; H, 5.80; N, 2.78. Found:
C, 78.86; H, 5.88; N, 2.74.
4. Qian-Cutrone, J.; Gao, Q.; Huang, S.; Klohr, S. E.; Veitch, J. A.; Shu,
Y.-Z. J. Nat. Prod. 1994, 57, 1656e1660.
5. (a) Okabe, K.; Yamada, K.; Yamamura, D.; Takada, S. J. Chem. Soc. C
1967, 2201e2206; (b) Nakanishi, K. Pure Appl. Chem. 1967, 14, 89e113.
6. (a) Greenlee, W. J.; Woodward, R. B. J. Am. Chem. Soc. 1976, 98,
6075e6076; (b) Boeckman, R. K.; Ko, S. S. J. Am. Chem. Soc. 1980,
102, 7146e7149; (c) Ichihara, A.; Ubukata, M.; Oikawa, H.; Murakami,
K.; Sakamura, S. Tetrahedron Lett. 1980, 21, 4469e4472; (d) Taunton,
J.; Wood, J. L.; Schreiber, S. L. J. Am. Chem. Soc. 1993, 115,
10378e10379; (e) Myers, A. G.; Tom, N. J.; Fraley, M. E.; Cohen,
S. B.; Madar, D. J. J. Am. Chem. Soc. 1997, 119, 6072e6094; (f) Shair,
M. D.; Yoon, T. Y.; Mosny, K. K.; Chou, T. C.; Danishefsky, S. J.
J. Am. Chem. Soc. 1996, 118, 9509e9525; (g) Uchiyama, M.; Kimura,
Y.; Ohta, A. Tetrahedron Lett. 2000, 41, 10013e10017; (h) Corey, E. J.;
Gavai, A. V. Tetrahedron Lett. 1988, 110, 649e651; (i) Crimmins,
M. T.; Pace, J. M.; Nantermet, P. G.; Kim-Meade, A. S.; Thomas, J. B.;
Watterson, S. H.; Wagman, A. S. J. Am. Chem. Soc. 2000, 122,
8453e8463.
4.4. Lewis acid-induced cyclization of propellane
intermediates 14aa, 14ab, 14ac, and 21
Theintermediates14aa, 14ab, 14ac, or21(0.1 mmol)anddry
THF(2 mL)were placed ina 30 mL flask. Theappropriate Lewis

1634
K. Asahi, H. Nishino / Tetrahedron 64 (2008) 1620e1634
7. (a) Clive, D. L. J.; Huang, X. J. Org. Chem. 2004, 69, 1872e1879; (b)
Srinivas, K. V. N. S.; Das, B. Synlett 2004, 1715e1718; (c) Zhang, W.;
Guo, Y.; Yang, L.; Liu, Z.-L. J. Chem. Res. 2004, 418e420; (d) Mahesh,
M. C.; Reddy, V.; Reddy, S.; Raju, P. V. K.; Reddy, V. V. N. Synth.
Commun. 2004, 34, 4089e4104; (e) Clive, D. L.; Huang, X. Tetrahedron
2002, 58, 10243e10250.
10. Nishino, H. Bioactive Heterocycles I; Eguchi, S., Ed.; Springer: Berlin,
2006; pp 39e76 and references cited therein.
11. Nguyen, V.-H.; Nishino, H. Tetrahedron Lett. 2004, 45, 3373e3377.
¨
12. Rogers, D.; Unal, G. G.; Williams, D. J.; Ley, S. V.; Sim, G. A.; Joshi,
B. S.; Ravindranath, K. R. J. Chem. Soc., Chem. Commun. 1979, 97e99.
13. Preliminary work: Asahi, K.; Nishino, H. Tetrahedron Lett. 2006, 47,
7259e7262.
8. (a) Snider, B. B. Chem. Rev. 1996, 96, 339e363; (b) Asahi, K.; Nishino,
H. Tetrahedron 2005, 61, 11107e11124; (c) Nishino, H. Bull. Chem. Soc.
Jpn. 1985, 58, 1922e1927; (d) Colombo, M. I.; Signorella, S.; Mischne,
M. P.; Gonzalez-Sierra, M.; Ruveda, E. A. Tetrahedron 1990, 46,
4149e4154; (e) Nguyen, V.-H.; Nishino, H.; Kurosawa, K. Tetrahedron
Lett. 1997, 38, 1773e1776; (f) Nguyen, V.-H.; Nishino, H.; Kurosawa,
K. Heterocycles 1998, 48, 465e480; (g) Chowdhury, F. A.; Nishino, H.;
Kurosawa, K. Heterocycles 1999, 51, 575e591; (h) Kumabe, R.; Nishino,
H.; Yasutake, M.; Nguyen, V.-H.; Kurosawa, K. Tetrahedron Lett. 2001,
42, 69e72; (i) Rahman, M. T.; Nishino, H. Org. Lett. 2003, 5,
2887e2890; (j) Rahman, M. T.; Nishino, H. Tetrahedron 2003, 59,
8383e8392; (k) Kumabe, R.; Nishino, H. Heterocycl. Commun. 2005,
10, 135e138; (l) Fujino, R.; Nishino, H. Synthesis 2005, 731e740; (m)
Chowdhury, F. A.; Nishino, H. J. Heterocycl. Chem. 2005, 42,
1337e1344; (n) Snider, B. B.; Smith, R. B. Tetrahedron 2002, 58,
25e34; (o) Tseng, C.-M.; Wu, Y.-L.; Chuang, C.-P. Tetrahedron 2004,
60, 12249e12260; (p) Zhou, H.; Huang, X.; Chen, W. J. Org. Chem.
2004, 69, 5471e5472; (q) Huang, J.-W.; Shi, M. J. Org. Chem. 2005,
70, 3859e3863; (r) Bar, G.; Parsons, A. F.; Thomas, C. B. Tetrahedron
2001, 57, 4719e4728; (s) Kumabe, R.; Nishino, H. Tetrahedron Lett.
2004, 45, 703e706.
14. Michael, J. P. Nat. Prod. Rep. 1999, 16, 697e709.
15. (a) Teshima, N.; Tsugawa, M.; Tateishi, A.; Tokumaru, M.; Matsubara, R.;
Kimachi, T.; Ju-ichi, M.; Ito, C.; Furukawa, H. Heterocycles 2004, 63,
2837e2843; (b) Dharmaratne, H. R. W.; Sotheeswaran, S.; Balasubrama-
niam, S.; Waight, E. S. Phytochemistry 1985, 27, 1553e1556; (c) Palmer,
C. J.; Josephs, J. L. J. Chem. Soc., Perkin Trans. 1 1995, 3135e3152.
16. Ouyang, J.; Nishino, H.; Kurosawa, K. J. Heterocycl. Chem. 1997, 34,
81e86.
17. (a) Ibenmoussa, S.; Chavignon, O.; Teulade, J.-C.; Viols, H.; Debouzy,
J.-C.; Chapat, J.-P.; Gueiffier, A. Heterocycl. Commun. 1998, 4, 317e
324; (b) Kametani, T.; Katoh, T.; Tsubuki, M.; Honda, T. Chem. Pharm.
Bull. 1985, 33, 61e66; (c) Tormena, C. F.; Rittner, R.; Abraham, R. J.
J. Phys. Org. Chem. 2002, 15, 211e217.
18. (a) Maini, N. P.; Sammes, P. M. J. Chem. Soc., Perkin Trans. 1 1988,
161e168; (b) Pirrung, C. M.; Webster, G. J. N. J. Org. Chem. 1987, 52,
3603e3613; (c) Stetter, H. Angew. Chem. 1995, 67, 769e788; (d) Naik,
N. R.; Amin, A. F.; Patel, S. R. J. Indian Chem. Soc. 1979, 56,
708e711; (e) Buckle, D. R.; Cantello, B. C. C.; Smith, H.; Spicer,
B. A. J. Med. Chem. 1975, 18, 726e732.
19. (a) Miyano, S.; Lu, D.-L. L.; Viti, M. S.; Sharpless, K. B. J. Org. Chem.
1985, 50, 4350e4360; (b) Zhou, J.-C.; Schenk, K. Helv. Chim. Acta 2002,
85, 1276e1283; (c) Jung, J.-C.; Jung, Y.-J.; Park, O.-S. Synth. Commun.
2001, 31, 1195e1200; (d) Bravo, P.; Ticozzi, C.; Cavicchio, G. Synthesis
1985, 9, 894e896; (e) Kannno, M.; Nakae, T.; Sakuyama, S.; Imaki, K.;
Nakai, H.; Hamanaka, N. Synlett 1997, 1472e1474.
9. (a) Nguyen, V.-H.; Nishino, H.; Kurosawa, K. Synthesis 1997, 899e908;
(b) Yamada, T.; Iwahara, Y.; Nishino, H.; Kurosawa, K. J. Chem. Soc.,
Perkin Trans. 1 1993, 609e616; (c) Nishino, H.; Nguyen, V.-H.; Yoshi-
naga, S.; Kurosawa, K. J. Org. Chem. 1996, 61, 8264e8271; (d) Bar,
G.; Parsons, A. F.; Thomas, C. B. Org. Biomol. Chem. 2003, 1, 373e380.