Facile endoperoxypropellane synthesis by manganese(III) acetate-mediated aerobic oxidation

Article abstract of DOI:10.1002/ejoc.200701232

Manganese(III)-catalyzed aerobic oxidation of combinations of 3-(2-oxoethyl)piperidine-2,4-diones and 1,1-diarylethenes at room temperature produced structurally interesting trioxaaza[ 4.4.3]propellanes in good yields. Similar reactions using 2-(2-oxoethyl)cyclohexane-1,3-diones also produced the corresponding endoperoxy[4.4.3]propellanes. On the other hand, 3-oxopropyl-substituted cycloalkane-1,3-diones did not give the desired propellanes, 1,2-dioxabicyclic propellane precursors were formed instead in excellent yields. The precursors could be converted into the corresponding propellanes in the presence of a Lewis acid. The mechanism for the formation of the propellanes is also described. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200701232

FULL PAPER
DOI: 10.1002/ejoc.200701232
Facile Endoperoxypropellane Synthesis by Manganese(III) Acetate-Mediated
Aerobic Oxidation
Kentaro Asahi[a] and Hiroshi Nishino*[b]
Dedicated to Professor emeritus Kazu Kurosawa
Keywords: Nitrogen heterocycles / Peroxides / Radicals / Cyclization / Oxidation
Manganese(III)-catalyzed aerobic oxidation of combinations
of 3-(2-oxoethyl)piperidine-2,4-diones and 1,1-diarylethenes
at room temperature produced structurally interesting trioxa-
aza[4.4.3]propellanes in good yields. Similar reactions using
not give the desired propellanes, 1,2-dioxabicyclic pro-
pellane precursors were formed instead in excellent yields.
The precursors could be converted into the corresponding
propellanes in the presence of a Lewis acid. The mechanism
2-(2-oxoethyl)cyclohexane-1,3-diones also produced the cor- for the formation of the propellanes is also described.
responding endoperoxy[4.4.3]propellanes. On the other
hand, 3-oxopropyl-substituted cycloalkane-1,3-diones did
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
lanes have also been isolated and synthesized.[9] In this pa-
per we describe the full results of the selective synthesis of
endoperoxypropellanes, and the related reaction.[10]
Introduction
A tricyclic system connected by a common carbon–car-
bon single bond is generally called a “propellane,”[1] and
such systems are found in many different categories of natu-
ral products,[1] some of which exhibit biological and phar-
macological activities.[2] Many synthetic chemists have
therefore investigated the synthesis of these natural prod-
ucts,[3] as well as their physical characteristics.[4] Very re-
cently, we developed a convenient synthesis of heterocyclic
propellanes 3 through the oxidation of 2-oxoethyl-substi-
tuted piperidine-2,4-diones and their derivatives with man-
ganese(III) acetate in the presence of 1,1-diarylethenes
(Scheme 1).[5] In these reactions, small amounts of the
unique endoperoxypropellanes 4 were produced at the same
time.[6] Although the formation of 4 could be avoided by
removal of the dissolved molecular oxygen in the reaction
solvent,[5,6] we were very interested in the nitrogen-contain-
ing endoperoxypropellanes 4 as an attractive synthetic tar-
get, since the endoperoxide skeleton is found in metabolites
and biologically active substances,[7] such as the naturally
occurring artemisinin, a well known potent antimalarial
agent.[8] In addition, a wide variety of natural azapropel-
Scheme 1. Oxidation of 2-oxoethyl-substituted piperidine-2,4-di-
ones 2 with manganese(III) acetate in the presence of 1,1-diaryleth-
enes 1 at reflux temperature.
Results and Discussion
We first adopted conventional aerobic oxidation condi-
tions[6] for the reactions between alkenes 1 and piperidine-
diones 2. The reaction between 1,1-diphenylethene (1a)
(0.25 mmol) and 1-isopropyl-3-(2-oxo-2-phenylethyl)piper-
idine-2,4-dione (2a, 0.5 mmol), for example, was carried out
in the presence of manganese(III) acetate dihydrate
(0.2 mmol) in glacial acetic acid (10 mL) at room tempera-
ture in air. After chromatographic separation, the desired
azatrioxa[4.4.3]propellane 4aa was isolated in a 42% yield,
along with by-product 5aa (30%) (Scheme 2 and Scheme 3,
and Table 1, Entry 1).
[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
Fax: +81-96-342-3374
E-mail: nishino@sci.kumamoto-u.ac.jp
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
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Facile Endoperoxypropellane Synthesis
Table 1. Reactions between 1,1-diarylethenes 1a–f and 3-(2-oxoethyl)piperidine-2,4-diones 2a–i in the presence of manganese(III) acetate.[a]
[b]
Entry
Alkene 1
Piperidinedione 2
1/2/Mn(OAc)3
Time (h)
Product (% yield)[c]
1[d]
2
3
4
5
6
7
8
9
10
11
12
13
14[e]
15
16[e]
17
18[e]
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1c
1d
1e
1e
1e
1e
1f
2a
2a
2b
2c
2d
2e
2f
1:2:0.8
1:2:0.8
1:1.5:0.8
1:2:0.7
1:2:0.7
1:2:1
4.5
7.5
7.5
7.5
7.5
7.5
7.5
7.5
7.5
7.5
7.5
7.5
7.5
5
4aa (42)
4aa (67)
4ab (67)
4ac (75)
4ad (68)
4ae (58)
4af (66)
4ag (67)
4ah (62)
4bb (67)
4cb (58)
4db (63)
4eb (11)
4eb (53)
4ei (8)[f]
4ei (19)[g]
4fi (71)[h]
4fi (26)[i]
5aa (30)
1:2:1
1:2:1
2g
2h
2b
2b
2b
2b
2b
2i
1:2:0.7
1:1.6:0.7
1:1.4:0.7
1:1.6:0.7
1:1.6:0.7
1:1.6:0.7
1:1.6:0.7
1:1.6:0.7
1:2:0.7
1:2:0.7
6eb (83)
6ei (65)
5eb (38)
5ei (60)
5fi (64)
7.5
3.5
7.5
6
2i
2i
1f
2i
[a] The reactions between compounds 1 (0.25 mmol) and compounds 2 were carried out in glacial acetic acid (10 mL) in the presence of
manganese(III) acetate dihydrate in air at room temperature for 7 h, followed by heating at 100 °C for 30 min, except in the cases of
Entries 1, 14, 16, and 18. [b] Molar ratio. [c] Isolated yield based on the amount of the alkene 1 used. [d] The reaction mixture was stirred
in air for 4.5 h at room temperature, and the solvent was then removed in vacuo. [e] The reaction was carried out in air at room
temperature until the alkene 1 had been completely consumed, followed by rapid quenching with water. [f] The corresponding dioxapropel-
lane 3ei was also isolated in 16% yield.[5] [g] The corresponding dioxapropellane 3ei was also isolated in 11% yield.[5] [h] The corresponding
dioxapropellane 3fi was also isolated in 12% yield.[5] [i] The corresponding dioxapropellane 3fi was also isolated in 4% yield.[5]
Scheme 2. MnIII-mediated aerobic oxidation of a combination of
1,1-diarylethenes 1 and 3-(2-oxoethyl)piperidine-2,4-diones 2 at
room temperature.
Scheme 3. Acid-catalyzed decomposition of azatrioxapropellanes
4aa, 4af or the propellane precursors 5.
The by-product 5aa showed very complicated NMR
spectra in CDCl3 or [D6]DMSO. In the IR spectrum, the
absorption band of the hydroxy group appeared at 3150–
3600 cm–1. However, the absorption band due to the car- composition was examined in perchloric acid/acetonitrile or
bonyl group only appeared at ν = 1618 cm–1. From these manganese(II) acetate/acetic acid at reflux temperature, and
˜
spectroscopic data, the by-product 5aa seemed to be an quantitatively gave the corresponding 3,3-bis(2-oxoethyl)-
equilibrium mixture of the hydroperoxide and a pair of piperidine-2,4-dione 6aa and phenol (Scheme 3 and Table 2,
hemiketals (see Scheme 3 and Supporting Information). In Entry 1).[6c,11] A similar reaction of 4aa also gave the same
order to confirm the structure of 5aa, its acid-catalyzed de- product (Table 2, Entry 2). It was postulated that a typical
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K. Asahi, H. Nishino
FULL PAPER
hydroperoxide and endoperoxide rearrangement had oc-
curred, and we therefore concluded that the by-product 5aa
was the precursor of 4aa. Furthermore, combustion analy-
sis of 5aa also agreed with the molecular formula (see Exp.
Sect.). Since continuous heating (10 min) after the oxidation
was effective for the dioxapropellane synthesis,[5] we at-
tempted heating at 100 °C after the aerobic oxidation in
order to convert the precursor 5aa into the endoperoxypro-
pellane 4aa in situ. As a result, the single product 4aa was
isolated in 67% yield (Table 1, Entry 2).
Scheme 4. MnIII-catalyzed aerobic oxidation of a combination of
1,1-diphenylethene (1a) and 5-(2-oxoethyl)barbituric acid 7 at room
temperature.
Table 2. Acid-catalyzed decomposition of azatrioxapropellanes 4aa
and 4af and hydroperoxide intermediates 5aa, 5eb, 5ei, and 5fi.[a]
the H-5 methylene protons (δ = 2.69 ppm) seemed to be
shielded by the anisotropic effect for the alkenic double
bond of the dihydrofuran ring. The most characteristic
peak of the sp2 proton (H-13) appeared at δ = 5.13 ppm (s,
1 H). In the 13C NMR spectrum, the characteristic down-
field peak at δ = 111.8 ppm was assigned to the C-1 quater-
nary ketal carbon together with an amide carbonyl carbon
(δ = 169.3 ppm) and an sp2 carbon (C-12) attached to the
furan oxygen (δ = 156.3 ppm). The quaternary carbon (C-
4) connected to the endoperoxy oxygen and the quaternary
carbon (C-6) at the ring junction also appeared at δ = 86.0
and δ = 54.7 ppm, respectively. All the peaks in the NMR
spectra were correlated by the H-H COSY and H-C COSY
spectra. In addition, the absorption band at 1639 cm–1 was
assigned to the amide carbonyl in the IR spectrum, while
the positive FAB mass spectrum and the elemental analysis
agreed with the molecular formula. Therefore, the structure
of 4ab was determined to be 8-benzyl-4,4,12-triphenyl-
2,3,11-trioxa-8-azatricyclo[4.4.3.01,6]tridec-12-en-7-one.
Having established the optimum conditions, we applied
the endoperoxypropellane formation to various 2-(2-oxo-
ethyl)cycloalkane-1,3-diones 9a–e (Scheme 5). Firstly, the
Product (%
Entry Substrate Reagent
Solvent Time
yield)[b,c]
1
2
3
4
5
6
5aa
4aa
4af
5eb
5ei
60% HClO4 aq. CH3CN 15 min
60% HClO4 aq. CH3CN 15 min
60% HClO4 aq. CH3CN 15 min
6aa (quant.)
6aa (quant.)
6af (92)
6eb (75)
6ei (63)
Mn(OAc)2·4H2O AcOH
Mn(OAc)2·4H2O AcOH
15 min
2 h
5fi
60% HClO4 aq. CH3CN 15 min
6Јfi (96)
[a] The reactions of 4 or 5 (0.1 mmol) were carried out in CH3CN
or AcOH (2 mL) in the presence of perchloric acid aqueous solu-
tion (60%, 0.3 mL) or manganese(II) acetate tetrahydrate (2 equiv.)
at reflux temperature. [b] Isolated yield based on the amount of the
substrate used. [c] The corresponding phenol was also produced.
Similar reactions of other combinations of alkenes 1a–f
and piperidinediones 2b–i were next investigated, and the
corresponding azatrioxapropellanes 4 were produced in
moderate to good yields except when 1e was used (Table 1,
Entries 3–14 and 17). Even under optimized conditions, the
endoperoxypropellane 4eb was only produced in 11% yield
in this last case, along with a large amount of the rearrange-
ment product 6eb (83%) (Table 1, Entry 13). This would
presumably be due to the electron-releasing properties of
the 4-methoxyphenyl group, which would accelerate re-
arrangement.[11a] The problem was partially avoided by ra-
pid quenching with water after the alkene 1e had been com-
pletely consumed during the aerobic oxidation (Table 1, En-
try 14). The use of the bulky substituents in the alkene 1f
and the piperidinedione 2i also led to the production of
a large amount of the propellane precursors 5ei and 5fi,
respectively (Table 1, Entries 16 and 18). Although the
NMR spectra of 5ei and 5fi were also complicated, the pre-
cursors 5ei and 5fi underwent acid-catalyzed decomposition
to give 6ei and 6Јfi (Scheme 3 and Table 2, Entries 5,6).[12]
Incidentally, it is well known that the aerobic oxidation of
barbituric acids does not give the endoperoxides, but hydro-
peroxides.[13] In fact, 5-(2-oxoethyl)barbituric acid (7) pro-
duced the corresponding hydroperoxide 8 under the same
conditions (Scheme 4). These results also supported the
structure of the intermediates 5.
The obtained azatrioxa[4.4.3]propellanes 4 were charac-
terized by spectroscopic methods and elemental analysis.
For example, the 1H NMR spectrum of 4ab showed the
presence of two sets of an AB quartet of benzyl protons
and H-5 methylene protons at δ = 4.71 (d, J = 14.9 Hz, 1
H), 4.37 (d, J = 14.9 Hz, 1 H), 3.86 (d, J = 14.3 Hz, 1 H),
Scheme 5. MnIII-catalyzed aerobic oxidation of a combination of
alkenes 1 and 2-(2-oxoethyl)cyclohexane-1,3-diones 9 at room tem-
and 2.69 ppm (d, J = 14.3 Hz, 1 H), respectively. One of perature.
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Facile Endoperoxypropellane Synthesis
reaction between 2-(2-oxo-2-phenylethyl)cyclohexane-1,3- of X-ray crystallographic analysis to be due to intramolecu-
dione (9a) and 1a was examined, and the desired propellane lar hydrogen bonding between the hydroperoxy groups and
10aa was obtained in 45% yield (Table 3, Entry 1).
the carbonyl oxygen atoms.[6,13,14]
Table 3. Similar aerobic oxidations with 2-(2-oxoethyl)cycloalkane-
1,3-diones 9a–e.[a]
Entry Substrate
Molar ratio[b] Time [h] Product (% yield)[c]
1
2
3
4
5
6
1a
1a
1a
1a
1a
1a
1a
1g
1h
1i
9a
9a
9a
9b
9c
9d
9e
9a
9a
9a
9a
1:2:0.4
1:2:0.4
1:2:0.4
1:2:0.4
1:2:0.4
1:2:0.4
1:2:0.1
1:2:0.4
1:2:0.4
5:1:0.3
1:2:0.1
10.5
5.5
1
1
2
10aa (45)
10aa (67)
10aa (83)
10ab (75)
10ac (78)[d]
10ad (75)
11 (85)
2
7
2.5
1.25
1.5
1.75
5.5
8[e]
9
10ga (61)[f]
10ha (28)[g]
10ia (9)
10[e]
11[h]
1j
10ja (32)[f]
Scheme 6. MnIII-catalyzed aerobic oxidation of 4-hydroxy-3-(2-
oxoethyl)-1H-quinolin-2-one (12) at room temperature.
[a] The reactions between compounds 1 (0.25 mmol) and com-
pounds 9 were carried out in glacial acetic acid (10 mL) in the
presence of manganese(III) acetate dihydrate in air at room tem-
perature for 0.5–10 h, followed by heating at 100 °C for 30 min,
except in the cases of Entries 8 and 10. [b] 1/9/Mn(OAc)3. [c] Iso-
lated yield based on the amount of the alkene 1 used. [d] A single
regioisomer was obtained. [e] After stirring for 1–1.5 h, the reaction
mixture was heated at 100 °C for 15 min. [f] Two diastereoisomers
were isolated in a ratio of ca. 1:2. [g] One diastereoisomer was
produced. [h] The alkene 1j (42%) was recovered.
In an attempt to apply the endoperoxypropellane synthe-
sis to the 3-oxopropyl-substituted cyclic 1,3-diones, we ex-
amined the reaction between 2-(3-oxo-3-phenylpropyl)-
cyclopentane-1,3-dione (15a) and 1a under standard aero-
bic conditions (Scheme 7). Surprisingly, the desired pro-
When the oxidation was scrutinized, however, it was
found that the reaction was finished in 30 min, and the sub-
sequent heating at 100 °C for 30 min gave 10aa in 83% yield
(Entry 3). Other 2-(2-oxoethyl)cyclohexane-1,3-diones 9b–e
also gave the corresponding propellanes 10 and 11 in good
yields (Entries 4–7). In the case of 9c, only a single re-
gioisomer 10ac was produced (Entry 5). The carboxylate 9e
yielded the propellanelactone 11 instead of the dihydrofu-
ran-fused propellane (Entry 7). The reactions of α-methyl-
styrene (1g) and 2-aminoacrylate 1j with 9a afforded 10ga
and 10ja, respectively, as ca. 1:2 mixture of diastereomers
(Entries 8 and 11). The reaction between styrene (1h) and
2-ethylbut-1-ene (1i) became messy and a small amount of
10ha and 10ia was obtained (Entries 9 and 10). The ap-
proach to the trioxa[5.4.3]propellane with 2-(2-oxo-2-phen-
ylethyl)cycloheptane-1,3-dione and 1a failed, with a com-
plex mixture being formed along with a large amount of
recovered 1a. 4-Hydroxy-3-(2-oxoethyl)-1H-quinolin-2-one
12 gave the endoperoxypropellane 13 (53% yield) together
with a considerable amount of the hydroperoxide interme-
diate 14 (37% yield; Scheme 6). When the reaction was
quenched by addition of water without subsequent heating,
the hydroperoxide intermediate 14 was isolated in 76%
yield. The isolation of the stable hydroperoxide 14 could be
explained by our previous studies.[6a,13,14] Similar reactions
with quinolinone derivatives without substituents at the 3-
position yielded the stable 3,3-bis(2-hydroperoxyethyl)-1H-
quinoline-2,4-diones.[6a] Barbituric acids and pyrazolidine-
3,5-diones also provided the stable 5,5-bis(2-hydroperoxy-
ethyl)barbituric acids[13] and 4,4-bis(2-hydroperoxyethyl)-
pyrazolizine-3,5-diones,[14a,14b] respectively. The unusual
Scheme 7. Similar aerobic oxidation with 3-oxopropyl-substituted
stabilities of the hydroperoxy groups turned out on the basis cyclic 1,3-diones 15a–f.
Eur. J. Org. Chem. 2008, 2404–2416
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K. Asahi, H. Nishino
FULL PAPER
pellane was not obtained, but only the acid-decomposition to acids,[11] the cyclizations were scrutinized very carefully.
product 17a was isolated (Table 4, Entry 1). However, rapid Use of a weak Lewis acid silica gel resulted in no change
quenching with water without the additional heating after in the reaction of 16b (Table 5, Entry 1), while use of p-
the alkene 1a had been consumed led to the production of toluenesulfonic acid in dry chloroform led to the decompo-
the dioxabicyclic intermediate 16a, which was the precursor sition of 16b to give the triketone 17b (Entry 2). However,
of the endoperoxypropellane (Entry 2). Similar treatment of use of p-toluenesulfonic acid at 0 °C gave the desired endop-
2-(3-oxopropyl)cyclohexane-1,3-diones 15b and 15c, cyclo- eroxypropellane 18b together with unchanged 16b (En-
hexenylpropanoate 15d, and 3-(3-oxopropyl)quinolinone try 4). Dry tetrahydrofuran was found to be the best solvent
15e also gave the corresponding propellane precursors 16b– to afford 18b in the presence of boron trifluoride (Entries 5–
e (Entries 3–6).[6a] In spite of rapid quenching with water, 10). Finally, it was found that conducting the reaction in
3-(3-oxopropyl)coumarin 15f quantitatively gave the acid the presence of ethylaluminium dichloride in dry tetra-
decomposition product 17f along with generation of the hydrofuran gave the best result for cyclizing compounds 16,
phenol. In any event, we were unable to achieve the synthe- with the desired endoperoxypropellanes 18a–c being ob-
sis of the endoperoxypropellanes from these 3-oxopropyl- tained in good yields (Entries 11–13). To our surprise, the
substituted cyclic 1,3-diones under the aerobic oxidation quinolinone-fused endoperoxide 16e afforded not the endo-
conditions.[6c,11]
peroxypropellane, but the dioxapropellane 19, the selective
synthesis of which had already been developed in our pre-
vious study (Entry 14).[5]
Table 4. Similar aerobic oxidation with 3-oxopropyl-substituted cy-
clic 1,3-diones 15a–f.[a]
Entry Substrate Molar ratio[b] Time [h] Product (% yield)[c]
1[d]
2
3
4
5
15a
15a
15b
15c
15d
15e
15f
1:2:0.5
1:2:0.5
1:2:0.4
1:2:0.4
1:1.5:0.1
1:2:0.5
1:2:0.5
1.5
1
2
3.5
21
1
17a (34)
16a (94)
16b (99)
16c (98)
16d (64)
16e (96)
17f (99)
6
7
1
[a] The reaction between 1a (0.25 mmol) and 15 was carried out in
glacial acetic acid (10 mL) in the presence of manganese(III) ace-
tate dihydrate in air at room temperature until 1a had been com-
pletely consumed, followed by rapid quenching with water except
for in the case of Entry 1. [b] 1/15/Mn(OAc)3. [c] Isolated yield
based on the amount of 1a used. [d] After stirring for 1 h, the
reaction mixture was heated under reflux for 30 min.
Scheme 8. Cyclizations of 3-oxopropyl-substituted propellane pre-
cursors 16 in the presence of Lewis acids.
Recently, we reported the efficient cyclization of 3-oxo-
propyl-substituted propellane precursors into the corre-
sponding dioxapropellanes in the presence of Lewis ac-
We believe that the mechanism for the formation of these
ids,[5b] and so we examined cyclizations of the 3-oxopropyl- endoperoxypropellanes involves the initial formation of a
substituted dioxabicyclic intermediates 16 for conversion manganese(III) enolate complex A by ligand exchange of
into the desired endoperoxypropellanes (Scheme 8 and the cyclic triketones such as 2, followed by electron transfer
Table 5). However, since the endoperoxides were sensitive from the electron-rich alkene 1 to the manganese(III)
Table 5. Cyclizations of 3-oxopropyl-substituted bicyclic endoperoxides 16 in the presence of Lewis acids.[a]
Entry
Endoperoxide Lewis acid
Solvent
Conditions
% Recovery Product (% yield)[b]
1
2
3
4
5
6
7
8
16b
16b
16b
16b
16b
16b
16b
16b
16b
16b
16b
16a
16c
16e
silica gel[c]
dry CHCl3
dry CHCl3
dry CHCl3
dry CHCl3
dry CHCl3
dry CCl4
dry MeCN
dry THF
dry THF
dry THF
dry THF
dry THF
dry THF
dry THF
room temp. (2.5 h), reflux (2 h)
reflux (15 min)
room temp. (11 h)
0 °C (5 h)
0 °C (3 h)
0 °C (1 h)
0 °C (2 h)
reflux (20 min)
30–40 °C (3 h)
0 °C (2 h), room temp. (9 h)
room temp. (30 min), 50–55 °C (1 h)
room temp. (30 min), 60 °C (1 h)
room temp. (30 min), 60 °C (1 h)
room temp. (30 min), 60 °C (1 h)
100
pTsOH (0.5 equiv.)
pTsOH (0.5 equiv.)
pTsOH (10 equiv.)
BF3·OEt2 (4 equiv.)
BF3·OEt2 (3 equiv.)
BF3·OEt2 (3 equiv.)
BF3·OEt2 (4 equiv.)
BF3·OEt2 (5 equiv.)
BF3·OEt2 (4 equiv.)
EtAlCl2 (5 equiv.)
EtAlCl2 (4 equiv.)
EtAlCl2 (4 equiv.)
EtAlCl2 (4 equiv.)
17b (72)
17b (52)
25
44
18b (35)
18b (47)
17b (80)
Complex mixture
17b (94)
17b (31)
17b (16)
18b (63)
9
18b (84)
18b (56)
18b (95)
18a (65)
18c (97)
19 (66)
10
11
12
13
14
31
[a] The cyclization of 16 (0.1 mmol) was carried out in dry solvent (2 mL) in air. [b] Isolated yield based on the amount of 16 used.
[c] Wakogel B-10 was used.
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Facile Endoperoxypropellane Synthesis
enolate complex to produce the carbon radical
B
Experimental Section
(Scheme 9).[11,15,16] Trapping with the triplet molecular oxy-
gen dissolved in the solvent would produce the peroxy radi-
cal C, which would be reduced by manganese(II) species D
in the reaction mixture to generate the peroxy anion E.[6b,6c]
Cyclization at the most favourable position of the carbonyl
group in E would result in the equilibrium with the endo-
peroxide anion F. Subsequent attack of the anion F on the
terminal carbonyl group gives the endoperoxypropellane 4
by dehydration. As a result, since the manganese(III) spe-
cies A could be reproduced, the autoxidation system would
be completed in the presence of the MnIII–MnII redox cata-
lysts. The thirty minute heating at 100 °C after the autoxi-
dation was needed to allow the intramolecular cyclization
followed by dehydration, and finally to produce the thermo-
dynamically stable endoperoxypropellanes 4.
General: The NMR spectra were recorded with a JNM EX300
FT NMR spectrometer at 300 MHz for 1H and at 75 MHz for 13C,
with tetramethylsilane as the internal standard. The chemical shifts
are reported in δ values (ppm). The IR spectra of neat samples
were measured by the ATR method with a Shimadzu 8400 FT IR
spectrophotometer and MIRacle A, and are expressed in cm–1. The
EI MS spectra were recorded with a Shimadzu QP-5050A gas chro-
matograph/mass spectrometer at the ionizing voltage of 70 eV. The
high-resolution mass spectra were measured at the Institute for
Materials Chemistry and Engineering, Kyushu University, Fuku-
oka, Japan. The elemental analyses were performed at the Analyti-
cal Center of Kumamoto University, Kumamoto, Japan. Manga-
nese(II) acetate tetrahydrate was purchased from Wako Pure
Chemical Ind., Ltd. Manganese(III) acetate dihydrate was prepared
by the method described in the literature.[5,6,16] The alkenes 1 were
synthesized as described in the literature,[16c,17] except for 1g, 1h
and 1i, which were purchased from Tokyo Kasei Co., Ltd. 3-(2-
Oxoethyl)piperidine-2,4-diones 2a–i, 2-(2-oxoethyl)cycloalkane-
1,3-diones 9a–e, 3-(2-oxoethyl)-1H-quinolin-2-one 12, 2-(3-oxopro-
pyl)cycloalkane-1,3-diones 15a–d, 3-(3-oxopropyl)-1H-quinolin-2-
one 15e and 3-(3-oxopropyl)coumarin derivative 15f were prepared
by treatment of the corresponding cyclic 1,3-diones with the appro-
priate 2-bromoethanones or 1-aryl-3-(dimethylamino)propan-1-
ones.[5,18,19]
Manganese(III)-Catalyzed Aerobic Oxidation of Combinations of
Alkenes 1a–f and 3-(2-Oxoethyl)piperidine-2,4-diones 2a–i at Room
Temperature in Air (General Procedure): An alkene 1 (0.25 mmol),
a 3-(2-oxoethyl)piperidine-2,4-dione 2 (0.5 mmol) and glacial acetic
acid (10 mL) were placed in a 50 mL round-bottomed flask, and
manganese(III) acetate dihydrate (0.17–0.25 mmol) was added. The
mixture was stirred at room temperature in air until the alkene 1
had been completely consumed (normally for 7 h or less), and was
then heated at 100 °C for 30 min. The solvent was removed in
vacuo, and the residue was triturated with water followed by extrac-
tion with chloroform (10 mLϫ3). The combined extracts were
dried with anhydrous magnesium sulfate and were then concen-
trated to dryness. The products were separated by TLC on silica
gel (Wakogel B-10) with elution with chloroform. The obtained en-
doperoxypropellanes 4 were further purified by recrystallization
from the appropriate solvents.
Scheme 9. Proposed mechanism for the MnIII-catalyzed aerobic
oxidation of 3-(2-oxoethyl)piperidine-2,4-diones 2 in the presence
of alkenes 1.
8-Isopropyl-4,4,12-triphenyl-2,3,11-trioxa-8-azatricyclo[4.4.3.01,6]-
tridec-12-en-7-one (4aa): Rf = 0.40 (chloroform). Colourless oil. 1H
NMR (300 MHz, CDCl3): δ = 7.55–7.52 (m, 2 H, arom. H), 7.42–
7.11 (m, 13 H, arom. H), 5.08 (s, 1 H, 13-H), 4.77 [sept., J = 6.8 Hz,
1 H, N–CH(CH3)2], 3.77 (d, J = 14.3 Hz, 1 H, 5-H), 3.25–3.18 (m,
2 H, 9-H), 2.64 (d, J = 14.3 Hz, 1 H, 5-H), 2.32 (ddd, J = 13.6,
3.5, 3.1 Hz, 1 H, 10-H), 1.93 (ddd, J = 13.6, 8.4, 7.2 Hz, 1 H, 10-
H), 1.07 [d, J = 6.8 Hz, 3 H, N–CH(CH3)2], 1.03 [d, J = 6.8 Hz, 3
H, N–CH(CH3)2] ppm. 13C NMR (75 MHz, CDCl3): δ = 168.5
(C=O), 156.0 (C-12), 146.9, 143.8, 129.4 (3 C, arom. C), 129.0,
128.4, 128.3, 128.0, 127.1, 127.0, 125.5, 125.4, 125.3 (15 C, arom.
CH), 111.6 (C-1), 100.7, 100.5 (1 C, C-13), 86.0 (C-4), 54.7 (C-6),
44.6 [N-CH(CH3)2], 37.2 (C-9), 35.3 (C-5), 28.5 (C-10), 19.3, 19.2,
Conclusions
We have accomplished the selective synthesis of the aza-
trioxa- (4, 13) and trioxa[4.4.3]propellanes 10 and 11 by
manganese(III)-catalyzed aerobic oxidation with 1,1-diaryl-
ethenes and cyclic 1,3-dicarbonyl compounds possessing
oxoethyl substituents. The reaction is very simple and con-
venient, and can be performed under mild reaction condi-
tions, although a thirty-minute heating period at 100 °C is
needed after the oxidation in order to complete the pro-
pellane formation except in certain cases. The oxopropyl-
substituted diketones 15 did not afford the desired pro-
pellanes, but rather the dioxabicyclic intermediates 16.
However, we have achieved the transformation of the acid-
sensitive dioxabicyclic intermediates 16 into the corre-
sponding endoperoxypropellanes 18 by Lewis acid-induced
intramolecular cyclization.
19.1 [2 C, N–CH(CH ) ] ppm. IR (neat): ν = 1636 (C=O) cm–1.
˜
3 2
FAB HRMS (acetone/NBA): calcd. for C30H29NO4 468.2175 (M +
1); found 468.2155.
8-Benzyl-4,4,12-triphenyl-2,3,11-trioxa-8-azatricyclo[4.4.3.01,6]tri-
dec-12-en-7-one (4ab): Rf = 0.32 (chloroform). Colourless micro-
crystals (from diethyl ether), m.p. 166.5 °C. 1H NMR (300 MHz,
CDCl3): δ = 7.57–7.54 (m, 2 H, arom. H), 7.43–7.12 (m, 18 H,
arom. H), 5.13 (s, 1 H, 13-H), 4.71 (d, J = 14.9 Hz, 1 H, Ph–CH2),
Eur. J. Org. Chem. 2008, 2404–2416
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2409

K. Asahi, H. Nishino
FULL PAPER
4.37 (d, J = 14.9 Hz, 1 H, Ph–CH2), 3.86 (d, J = 14.3 Hz, 1 H, 5-
H), 3.38 (ddd, J = 12.7, 11.8, 2.8 Hz, 1 H, 9-H), 3.11 (ddd, J =
12.7, 4.6, 3.5 Hz, 1 H, 9-H), 2.69 (d, J = 14.3 Hz, 1 H, 5-H), 2.23
(ddd, J = 13.6, 3.5, 2.8 Hz, 1 H, 10-H), 1.95 (ddd, J = 13.6, 11.8,
4.6 Hz, 1 H, 10-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 169.3
(C=O), 156.3 (C-12), 146.8, 143.7, 136.3, 129.3 (4 C, arom. C),
8-Ethyl-4,4,12-triphenyl-2,3,11-trioxa-8-azatricyclo[4.4.3.01,6]tridec-
12-en-7-one (4af): Rf = 0.24 (chloroform). Colourless needles (from
diethyl ether/hexane), m.p. 153–154 °C. 1H NMR (300 MHz,
CDCl3): δ = 7.54–7.52 (m, 2 H, arom. H), 7.42–7.18 (m, 11 H,
arom. H), 7.16–7.11 (m, 2 H, arom. H), 5.08 (s, 1 H, 13-H), 3.76
(d, J = 14.3 Hz, 1 H, 5-H), 3.45 (ddd, J = 12.7, 11.7, 2.9 Hz, 1 H,
129.1, 128.7, 128.34, 128.27, 128.0, 127.7, 127.6, 127.1, 127.0, 9-H), 3.37 (dq, J = 21.7, 7.2 Hz, 2 H, N–CH2CH3), 3.15 (ddd, J =
125.42, 125.35, 125.2 (20 C, arom. CH), 111.8 (C-1), 100.5, 100.4 12.7, 4.7, 3.7 Hz, 1 H, 9-H), 2.64 (d, J = 14.3 Hz, 1 H, 5-H), 2.31
(1 C, C-13), 86.0 (C-4), 54.7 (C-6), 50.6 (Ph–CH2), 41.4 (C-9), 37.1 (ddd, J = 13.6, 3.7, 2.9 Hz, 1 H, 10-H), 2.01 (ddd, J = 13.6, 11.7,
(C-5), 27.9 (C-10) ppm. IR (neat): ν = 1639 (C=O) cm–1
C34H29NO4 (515.60): calcd. C 79.20, H 5.67, N 2.72; found C
79.33, H 5.60, N 2.74.
.
4.6 Hz, 1 H, 10-H), 1.06 (t, J = 7.2 Hz, 3 H, N–CH2CH3) ppm.
13C NMR (75 MHz, CDCl3): δ = 168.5 (C=O), 155.9 (C-12), 146.8,
143.7, 129.3 (3 C, arom. C), 129.0, 128.3, 128.2, 127.9, 127.0, 126.9,
125.4, 125.3, 125.2 (15 C, arom. CH), 111.8 (C-1), 100.62, 100.58
(1 C, C-13), 85.9 (C-4), 54.4 (C-6), 42.6 (N–CH2CH3), 41.6 (C-9),
˜
8-Benzyl-12-(4-chlorophenyl)-4,4-diphenyl-2,3,11-trioxa-8-azatricy-
clo[4.4.3.01,6]tridec-12-en-7-one (4ac): Rf = 0.64 (chloroform).
Colourless microcrystals (from diethyl ether/hexane), m.p. 205–
206 °C. 1H NMR (300 MHz, CDCl3): δ = 7.61–7.59 (m, 2 H, arom.
H), 7.55–6.99 (m, 17 H, arom. H), 5.11 (s, 1 H, 13-H), 4.70 (d, J
= 14.9 Hz, 1 H, Ph–CH2), 4.38 (d, J = 14.9 Hz, 1 H, Ph–CH2),
3.86 (d, J = 14.3 Hz, 1 H, 5-H), 3.36 (ddd, J = 12.7, 11.7, 2.6 Hz,
1 H, 9-H), 3.11 (ddd, J = 12.7, 4.4, 3.7 Hz, 1 H, 9-H), 2.67 (d, J =
14.3 Hz, 1 H, 5-H), 2.22 (ddd, J = 13.6, 3.7, 2.6 Hz, 1 H, 10-H),
1.96 (ddd, J = 13.6, 11.7, 4.4 Hz, 1 H, 10-H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 169.1 (C=O), 155.3 (C-12), 146.8, 143.7,
136.3, 134.9 (4 C, arom. C), 130.1, 128.9, 128.8, 128.6, 128.4, 128.3,
128.1 (arom. CH), 127.8 (arom. C), 127.7, 127.2, 127.1, 126.7,
125.3, 125.1 (arom. CH), 112.0 (C-1), 101.1 (1 C, C-13), 86.1 (C-
4), 54.8 (C-6), 50.7 (Ph–CH2), 41.5 (C-9), 37.0 (C-5), 27.9 (C-
37.0 (C-5), 28.0 (C-10), 12.2 (N–CH CH ) ppm. IR (neat): ν = 1636
˜
2
3
(C=O) cm–1. C29H27NO4·17/20 H2O (468.84): calcd. C 74.29, H
6.17, N 2.99; found C 74.46, H 6.47, N 2.83. FAB HRMS (acetone-
NBA): calcd. for C29H28NO4 454.2018 (M + 1); found 454.2010.
4,4,12-Triphenyl-8-propyl-2,3,11-trioxa-8-azatricyclo[4.4.3.01,6]tri-
dec-12-en-7-one (4ag): Rf = 0.31 (chloroform). Colourless micro-
crystals (from diethyl ether/hexane), m.p. 135–137 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.55–7.52 (m, 2 H, arom. H), 7.42–7.11
(m, 13 H, arom. H), 5.07 (s, 1 H, 13-H), 3.78 (d, J = 14.3 Hz, 1 H,
5-H), 3.46 (ddd, J = 12.8, 11.8, 2.2 Hz, 1 H, 9-H), 3.44–3.34 (m, 1
H, N–CH2CH2CH3), 3.26–3.19 (m, 1 H, N–CH2CH2CH3), 3.15
(ddd, J = 12.8, 4.4, 3.5 Hz, 1 H, 9-H), 2.63 (d, J = 14.3 Hz, 1 H,
5-H), 2.30 (ddd, J = 13.6, 3.5, 2.2 Hz, 1 H, 10-H), 2.02 (ddd, J =
13.6, 11.7, 4.4 Hz, 1 H, 10-H), 1.56–1.44 (m, 2 H, N–
10) ppm. IR (KBr): ν = 1647 (C=O) cm–1. C H ClNO (550.04):
˜
34 28
4
calcd. C 74.24, H 5.13, N 2.55; found C 74.08, H 5.41, N 2.51.
CH2CH2CH3), 0.84 (t, J = 7.5 Hz, 3 H, N–CH2CH2CH3) ppm. 13
C
8-Benzyl-12-(4-methylphenyl)-4,4-diphenyl-2,3,11-trioxa-8-azatricy-
clo[4.4.3.01,6]tridec-12-en-7-one (4ad): Rf = 0.62 (chloroform).
Colourless microcrystals (from diethyl ether/hexane), m.p. 190–
191 °C. 1H NMR (300 MHz, CDCl3): δ = 7.82–7.79 (m, 2 H, arom.
H), 7.56–7.02 (m, 17 H, arom. H), 5.06 (s, 1 H, 13-H), 4.69 (d, J
= 14.9 Hz, 1 H, Ph–CH2), 4.37 (d, J = 14.9 Hz, 1 H, Ph–CH2),
3.84 (d, J = 14.3 Hz, 1 H, 5-H), 3.38 (ddd, J = 12.3, 11.9, 2.4 Hz,
1 H, 9-H), 3.09 (ddd, J = 12.3, 4.6, 3.5 Hz, 1 H, 9-H), 2.68 (d, J =
14.3 Hz, 1 H, 5-H), 2.22 (ddd, J = 13.6, 3.5, 2.4 Hz, 1 H, 10-H),
1.94 (ddd, J = 13.6, 11.9, 4.6 Hz, 1 H, 10-H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 169.5 (C=O), 156.5 (C-12), 146.9, 143.8,
139.2, 136.4 (4 C, arom. C), 129.0, 128.8, 128.4, 128.0, 127.7, 127.6,
127.1, 127.0 (arom. CH), 126.6 (arom. C), 125.5, 125.3, 125.2
(arom. CH), 111.8 (C-1), 99.6 (C-13), 86.0 (C-4), 54.7 (C-6), 50.6
(Ph–CH2), 41.5 (C-9), 37.1 (C-5), 28.0 (C-10), 21.4 (CH3) ppm. IR
NMR (75 MHz, CDCl3): δ = 168.9 (C=O), 156.0 (C-12), 146.9,
143.8, 129.3 (3 C, arom. C), 129.0, 128.3, 128.0, 127.1, 126.9, 125.4,
125.3, 125.2 (15 C, arom. CH), 111.8 (C-1), 100.7, 100.6 (1 C, C-
13), 86.0 (C-4), 54.6 (C-6), 49.3 (N–CH2CH2CH3), 42.2 (C-9), 37.0
(C-5), 28.0 (C-10), 20.4 (N–CH2CH2CH3), 11.2, 11.0 (1 C, N–
CH CH CH ) ppm. IR (neat): ν = 1639 (C=O) cm–1. C H NO
˜
2
2
3
30 29
4
(467.56): calcd. C 77.06, H 6.25, N 3.00; found C 77.21, H 6.36, N
2.99. FAB HRMS (acetone/NBA): calcd. for C30H30NO4 468.2175
(M + 1); found 468.2090.
4,4,8,12-Tetraphenyl-2,3,11-trioxa-8-azatricyclo[4.4.3.01,6]tridec-12-
en-7-one (4ah): Rf = 0.40 (chloroform). Colourless needles (from
diethyl ether), m.p. 216 °C. 1H NMR (300 MHz, CDCl3): δ = 7.57–
7.55 (m, 2 H, arom. H), 7.54–7.12 (m, 18 H, arom. H), 5.17 (s, 1
H, 13-H), 3.84 (ddd, J = 12.5, 11.4, 2.8 Hz, 1 H, 9-H), 3.79 (d, J
= 14.3 Hz, 1 H, 5-H), 3.54 (ddd, J = 12.5, 4.4, 4.2 Hz, 1 H, 9-H),
2.82 (d, J = 14.3 Hz, 1 H, 5-H), 2.43 (ddd, J = 13.6, 4.2, 2.8 Hz, 1
H, 10-H), 2.24 (ddd, J = 13.6, 11.4, 4.4 Hz, 1 H, 10-H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 169.0 (C=O), 156.3 (C-12), 146.6,
143.7, 142.6, 132.4 (4 C, arom. C), 130.0, 129.23, 129.19, 128.4,
128.3, 128.2, 128.0, 127.1, 127.02, 126.96, 125.6, 125.43, 125.38,
125.3 (20 C, arom. CH), 111.7 (C-1), 100.4 (C-13), 85.9 (C-4), 55.0
(KBr): ν = 1647 (C=O) cm–1. C H NO (529.62): calcd. C 79.37,
˜
35 31
4
H 5.90, N 2.64; found C 79.52, H 5.97, N 2.52.
8-Methyl-4,4,12-triphenyl-2,3,11-trioxa-8-azatricyclo[4.4.3.01,6]tri-
dec-12-en-7-one (4ae): Rf = 0.27 (chloroform). Colourless micro-
crystals (from diethyl ether/hexane), m.p. 178–179 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.54–7.51 (m, 2 H, arom. H), 7.43–7.09
(m, 13 H, arom. H), 5.09 (s, 1 H, 13-H), 3.72 (d, J = 14.3 Hz, 1 H,
5-H), 3.48 (ddd, J = 12.5, 11.6, 2.9 Hz, 1 H, 9-H), 3.12 (ddd, J =
12.5, 4.6, 3.9 Hz, 1 H, 9-H), 2.92 (s, 3 H, N–CH3), 2.69 (d, J =
14.3 Hz, 1 H, 5-H), 2.29 (ddd, J = 13.6, 3.9, 2.9 Hz, 1 H, 10-H),
2.05 (ddd, J = 13.6, 11.6, 4.6 Hz, 1 H, 10-H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 169.1 (C=O), 155.9 (C-12), 146.6, 143.8,
129.3 (3 C, arom. C), 129.1, 128.3, 128.0, 127.1, 127.0, 125.4, 125.3
(C-6), 45.6 (C-9), 37.3 (C-5), 28.8 (C-10) ppm. IR (neat): ν = 1653
˜
(C=O) cm–1. C33H27NO4 (501.57): calcd. C 79.02, H 5.43, N 2.79;
found C 79.16, H 5.46, N 2.78.
8-Benzyl-4,4-bis(4-chlorophenyl)-12-phenyl-2,3,11-trioxa-8-azatricy-
clo[4.4.3.01,6]tridec-12-en-7-one (4bb): Rf = 0.47 (chloroform).
Colourless microcrystals (from diethyl ether/hexane), m.p. 150–
(15 C, arom. CH), 111.7 (C-1), 100.9, 100.7 (1 C, C-13), 85.9 (C- 151 °C. 1H NMR (300 MHz, CDCl3): δ = 7.57–7.13 (m, 18 H,
4), 54.2 (C-6), 44.2 (C-9), 37.1 (C-5), 35.55, 35.48 (1 C, N–CH3),
arom. H), 5.11 (s, 1 H, 13-H), 4.72 (d, J = 14.9 Hz, 1 H, Ph–CH2),
27.7 (C-10) ppm. IR (neat): ν = 1639 (C=O) cm–1. C28H25NO4 4.37 (d, J = 14.9 Hz, 1 H, Ph–CH2), 3.77 (d, J = 14.3 Hz, 1 H, 5-
˜
(439.50): calcd. C 76.52, H 5.73, N 3.19; found C 76.51, H 5.89, N
3.16. FAB HRMS (acetone-NBA): calcd. for C28H26NO4 440.1862
(M + 1); found 440.1763.
H), 3.39 (ddd, J = 12.7, 11.7, 2.4 Hz, 1 H, 9-H), 3.13 (ddd, J =
12.7, 4.4, 3.5 Hz, 1 H, 9-H), 2.64 (d, J = 14.3 Hz, 1 H, 5-H), 2.24
(ddd, J = 13.8, 3.5, 2.4 Hz, 1 H, 10-H), 1.94 (ddd, J = 13.8, 11.7,
2410
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 2404–2416

Facile Endoperoxypropellane Synthesis
4.4 Hz, 1 H, 10-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 169.0
(C=O), 156.7 (C-12), 145.0, 141.8, 136.2, 133.3, 133.2 (5 C, arom.
C), 129.4 (arom. CH), 129.0 (arom. C), 128.9, 128.8, 128.7, 128.5, methanol, 98:2, v/v). Colourless oil. H NMR (300 MHz, CDCl3):
8,12-Di-tert-butyl-4,4-bis(4-methoxyphenyl)-2,3,11-trioxa-8-aza-
tricyclo[4.4.3.01,6]tridec-12-en-7-one (4ei): Rf = 0.62 (chloroform/
1
128.3, 128.1, 128.0, 127.7, 127.0, 126.7, 125.4 (17 C, arom. CH),
111.9 (C-1), 100.0 (C-13), 85.4 (C-4), 54.6 (C-6), 50.7 (Ph–CH2),
δ = 7.40–7.25 (m, 4 H, arom. H), 6.84–6.74 (m, 4 H, arom. H),
4.34 (s, 1 H, 13-H), 3.75 (s, 3 H, OCH3), 3.74 (s, 3 H, OCH3), 3.66
41.4 (C-9), 36.9 (C-5), 27.8 (C-10) ppm. IR (neat): ν = 1645 (d, J = 14.5 Hz, 1 H, 5-H), 3.39 (ddd, J = 12.7, 4.2, 3.8 Hz, 1 H,
˜
(C=O) cm–1. C34H27Cl2NO4 (584.49): calcd. C 69.87, H 4.66, N
2.40; found C 69.87, H 4.45, N 2.33.
9-H), 3.20 (ddd, J = 12.7, 11.5, 2.4 Hz, 1 H, 9-H), 2.34 (d, J =
14.5 Hz, 1 H, 5-H), 2.13 (ddd, J = 13.7, 3.8, 2.4 Hz, 1 H, 10-H),
1.85 (ddd, J = 13.7, 11.5, 4.2 Hz, 1 H, 10-H), 1.39 [s, 9 H, N–
C(CH3)3], 0.97 [s, 9 H, C(CH3)3] ppm. 13C NMR (75 MHz, CDCl3)
δ = 171.1 (C=O), 167.0 (C-12), 158.3, 158.2, 140.3, 136.3 (4 C,
arom. C), 126.9, 126.1, 113.5, 113.0 (8 C, arom. CH), 111.1 (C-1),
97.7 (C-13), 85.8 (C-4), 57.8, 55.9 [2 C, C-6, N–C(CH3)3], 55.2, 55.1
(2 C, OCH3), 38.5 (C-9), 35.8 (C-5), 31.9 [C(CH3)3], 29.2 (C-10),
8-Benzyl-4,4-bis(4-fluorophenyl)-12-phenyl-2,3,11-trioxa-8-azatri-
cyclo[4.4.3.01,6]tridec-12-en-7-one (4cb): Rf = 0.62 (chloroform).
Colourless microcrystals (from diethyl ether/hexane), m.p. 177–
178 °C. 1H NMR (300 MHz, CDCl3): δ = 7.50–7.14 (m, 14 H,
arom. H), 7.05–7.00 (m, 2 H, arom. H), 6.89–6.84 (m, 2 H, arom.
H), 5.12 (s, 1 H, 13-H), 4.70 (d, J = 14.7 Hz, 1 H, Ph–CH2), 4.39
(d, J = 14.7 Hz, 1 H, Ph–CH2), 3.78 (d, J = 14.3 Hz, 1 H, 5-H),
3.39 (ddd, J = 12.7, 11.7, 2.6 Hz, 1 H, 9-H), 3.14 (ddd, J = 12.7,
4.6, 3.5 Hz, 1 H, 9-H), 2.64 (d, J = 14.3 Hz, 1 H, 5-H), 2.20 (ddd,
J = 13.6, 3.5, 2.6 Hz, 1 H, 10-H), 1.95 (ddd, J = 13.6, 11.7, 4.6 Hz,
1 H, 10-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 169.1 (C=O),
163.5, 163.3, 160.2, 160.0 (2 C, arom. C), 156.5 (C-12), 142.5, 139.4,
136.3, 136.2, 132.6 (3 C, arom. C), 129.3 (arom. CH), 129.1 (arom.
C), 128.8, 128.4, 127.7, 127.4, 127.3, 127.1, 126.9, 125.3 115.4,
115.2, 115.1, 114.8 (17 C, arom. CH), 111.8 (C-1), 100.2 (C-13),
85.5 (C-4), 54.7 (C-6), 50.7 (Ph–CH2), 41.5 (C-9), 37.2 (C-5), 27.9
28.2 [3 C, N–C(CH ) ], 27.2 [3 C, C(CH ) ] ppm. IR (KBr): ν =
˜
3 3
3 3
1647 (C=O) cm–1. FAB HRMS (acetone/NBA): calcd. for
C31H40NO6 522.2856 (M + 1); found 522.2855.
8,12-Di-tert-butyl-4,4-di(naphth-2-yl)-2,3,11-trioxa-8-azatricyclo-
[4.4.3.01,6]tridec-12-en-7-one (4fi): Rf = 0.42 (chloroform). Colour-
less microcrystals (from diethyl ether/hexane), m.p. 190–191 °C. 1H
NMR (300 MHz, CDCl3): δ = 8.14–7.39 (m, 14 H, arom. H), 4.34
(s, 1 H, 13-H), 3.96 (d, J = 14.7 Hz, 1 H, 5-H), 3.41 (ddd, J = 12.8,
4.4, 3.7 Hz, 1 H, 9-H), 3.22 (ddd, J = 12.8, 11.7, 2.6 Hz, 1 H, 9-
H), 2.61 (d, J = 14.7 Hz, 1 H, 5-H), 2.17 (ddd, J = 13.6, 3.7, 2.6 Hz,
1 H, 10-H), 1.87 (ddd, J = 13.6, 11.7, 4.4 Hz, 1 H, 10-H), 1.39 [s,
9 H, N–C(CH3)3], 0.93 [s, 9 H, C(CH3)3] ppm. 13C NMR (75 MHz,
CDCl3): δ = 171.1 (C=O), 167.4 (C-12), 144.6, 140.9, 133.0, 132.7,
132.4, 132.2 (6 C, arom. C), 128.3, 128.2, 128.1, 127.7, 127.5,
126.09, 126.05, 126.0, 125.9, 124.2, 124.1, 123.9, 123.3 (14 C, arom.
CH), 111.3 (C-1), 97.6 (C-13), 86.4 (C-4), 57.9, 56.1 [2 C, C-6, N–
C(CH3)3], 38.5 (C-9), 35.5 (C-5), 32.0 [C(CH3)3], 29.1 (C-10), 28.2
(C-10) ppm. IR (neat): ν = 1647 (C=O) cm–1. C34H27F2NO4
˜
(551.58): calcd. C 74.04, H 4.93, N 2.54; found C 74.16, H 5.07, N
2.47.
8-Benzyl-4,4-bis(4-methylphenyl)-12-phenyl-2,3,11-trioxa-8-aza-
tricyclo[4.4.3.01,6]tridec-12-en-7-one (4 db): Rf = 0.58 (chloroform).
Colourless microcrystals (from diethyl ether/hexane), m.p. 160–
161 °C. 1H NMR (300 MHz, CDCl3): δ = 7.46–7.13 (m, 16 H,
arom. H), 6.97–6.95 (m, 2 H, arom. H), 5.19 (s, 1 H, 13-H), 4.72
(d, J = 14.9 Hz, 1 H, Ph–CH2), 4.35 (d, J = 14.9 Hz, 1 H, Ph–
CH2), 3.81 (d, J = 14.3 Hz, 1 H, 5-H), 3.38 (ddd, J = 12.5, 11.9,
2.8 Hz, 1 H, 9-H), 3.13 (ddd, J = 12.5, 4.6, 3.7 Hz, 1 H, 9-H), 2.66
(d, J = 14.3 Hz, 1 H, 5-H), 2.30 (s, 3 H, CH3), 2.28 (ddd, J = 13.6,
3.7, 2.8 Hz, 1 H, 10-H), 2.23 (s, 3 H, CH3), 1.94 (ddd, J = 13.6,
11.9, 4.6 Hz, 1 H, 10-H) ppm. 13C NMR (75 MHz, CDCl3): δ =
169.5 (C=O), 156.2 (C-12), 144.3, 142.9, 140.9, 136.7, 136.6, 136.4,
135.2 (5 C, arom. C), 130.2 (arom. CH), 129.4 (arom. C), 129.04,
129.01, 128.9, 128.74, 128.66, 128.3, 127.7, 127.6 (17 C, arom. CH),
111.8 (C-1), 100.7 (C-13), 86.0 (C-4), 54.7 (C-6), 50.6 (Ph–CH2),
41.5 (C-9), 37.2 (C-5), 28.0 (C-10), 21.7, 21.0 (2 C, CH3) ppm. IR
[3 C, N–C(CH ) ], 27.3 [3 C, C(CH ) ] ppm. IR (KBr): ν = 1645
˜
3 3
3 3
(C=O) cm–1. C37H39NO4 (561.71): calcd. C 79.11, H 7.00, N 2.49;
found C 79.32, H 7.10, N 2.63.
Equilibrium Mixture 5aa: C30H31NO5 (485.57): calcd. C 74.21, H
6.43, N 2.88; found C 73.91, H 6.37, N 2.97.
Equilibrium Mixture 5eb: C36H35NO7 (593.67): calcd. C 72.83, H
5.94, N 2.36; found C 72.78, H 5.84, N 2.41.
Equilibrium Mixture 5ei: C31H41NO7·2/5H2O (546.87): calcd. C
68.08, H 7.71, N 2.56; found C 68.05, H 7.74, N 2.55.
Equilibrium Mixture 5fi: C37H41NO5 (579.73): calcd. C 76.66, H
7.13, N 2.42; found C 76.36, H 7.22, N 2.44.
(neat): ν = 1647 (C=O) cm–1. C H NO (543.65): calcd. C 79.53,
˜
36 33
4
H 6.12, N 2.58; found C 79.44, H 6.21, N 2.57.
General Procedure for the Acid-Catalyzed Decomposition of Trioxa-
azapropellanes 4 and Hydroperoxide Intermediates 5: A perchloric
acid solution (60%, 0.3 mL) was added to a solution of 4aa, 4af,
5aa or 5fi (0.1 mmol) in acetonitrile (2 mL), and the mixture was
8-Benzyl-4,4-bis(4-methoxyphenyl)-12-phenyl-2,3,11-trioxa-8-aza-
tricyclo[4.4.3.01,6]tridec-12-en-7-one (4eb): Rf = 0.49 (chloroform).
Colourless microcrystals (from diethyl ether/hexane), m.p. 173–
174 °C. 1H NMR (300 MHz, CDCl3): δ = 7.47–7.12 (m, 14 H, heated under reflux for 15 min. Water (20 mL) was added to the
arom. H), 6.87–6.84 (m, 2 H, arom. H), 6.70–6.67 (m, 2 H, arom.
H), 5.22 (s, 1 H, 13-H), 4.67 (d, J = 14.9 Hz, 1 H, Ph–CH2), 4.37
(d, J = 14.9 Hz, 1 H, Ph–CH2), 3.76 (s, 3 H, OCH3), 3.75 (d, J =
resulting solution to quench it, and the resulting aqueous solution
was extracted with chloroform (3ϫ10 mL). The combined chloro-
form extracts were dried with anhydrous magnesium sulfate and
14.3 Hz, 1 H, 5-H), 3.70 (s, 3 H, OCH3), 3.36 (ddd, J = 12.5, 11.7, concentrated to dryness. The obtained crude products were purified
2.8 Hz, 1 H, 9-H), 3.08 (ddd, J = 12.5, 4.4, 3.9 Hz, 1 H, 9-H), 2.68 by TLC on silica gel with elution with chloroform, giving 6aa
(d, J = 14.3 Hz, 1 H, 5-H), 2.21 (ddd, J = 13.6, 3.9, 2.8 Hz, 1 H,
(32.0 mg, quant.), 6af (34.7 mg, 92%) or 6Јfi (36.4 mg, 96%),
10-H), 1.94 (ddd, J = 13.6, 11.7, 4.4 Hz, 1 H, 10-H) ppm. 13C NMR respectively. The obtained products were further purified by
(75 MHz, CDCl3): δ = 169.4 (C=O), 158.4, 158.2 (2 C, arom. C), recrystallization from the appropriate solvents. The 5eb or 5ei
156.1 (C-12), 139.3, 136.3, 136.1, 129.3 (4 C, arom. C), 129.0, 128.7, (0.1 mmol) was also heated under reflux in acetic acid (2 mL) in
128.2, 127.6, 127.5, 126.9, 126.5, 125.3, 113.5, 113.2 (18 C, arom.
the presence of manganese(II) acetate tetrahydrate (0.2 mmol) for
CH), 111.6 (C-1), 100.7 (C-13), 85.7 (C-4), 55.14, 55.08 (2 C, 15 min or 2 h. Water (80 mL) was added to the resulting mixture,
OCH3), 54.6 (C-6), 50.5 (Ph–CH2), 41.4 (C-9), 37.3 (C-5), 27.9 (C- and the aqueous solution was extracted with chloroform
10) ppm. IR (KBr): ν = 1647 (C=O) cm–1. C H NO (575.65):
(3ϫ10 mL). The combined extracts were dried with anhydrous
˜
36 33
6
calcd. C 75.11, H 5.78, N 2.43; found C 74.88, H 5.86, N 2.46.
magnesium sulfate and concentrated to dryness. The obtained
Eur. J. Org. Chem. 2008, 2404–2416
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2411

K. Asahi, H. Nishino
FULL PAPER
crude products were purified by TLC on silica gel with elution with
chloroform, giving 6eb (35.2 mg, 75%) or 6ei (26.2 mg, 63%). The
obtained products were further purified by recrystallization from
the appropriate solvents.
C
29H27NO5 (469.53): calcd. C 74.18, H 5.80, N 2.98; found C
73.97, H 5.85, N 2.96.
1-tert-Butyl-3-(3,3-dimethyl-2-oxobutyl)-3-[2-(4-methoxyphenyl)-2-
oxoethyl]piperidine-2,4-dione (6ei): Rf = 0.44 (chloroform/methanol,
98:2, v/v). Colourless prisms (from ethyl acetate/hexane), m.p.
1-Isopropyl-3,3-bis(2-oxo-2-phenylethyl)piperidine-2,4-dione (6aa):
1
124.0–124.5 °C. H NMR (300 MHz, CDCl3): δ = 7.88–7.85 (m, 2
Rf = 0.44 (chloroform). Colourless microcrystals (from diethyl
H, arom. H), 6.91–6.88 (m, 2 H, arom. H), 3.85 (s, 3 H, OCH3),
3.87–3.82 (m, 2 H, 6-H), 3.77 (d, J = 16.5 Hz, 1 H, CH2), 3.50 (d,
J = 17.6 Hz, 1 H, CH2), 3.34 (d, J = 16.5 Hz, 1 H, CH2), 3.10 (d,
J = 17.6 Hz, 1 H, CH2), 3.07 (br. t, J = 6.2 Hz, 2 H, 5-H), 1.38 [s,
9 H, N–C(CH3)3], 1.11 [s, 9 H, C(CH3)3] ppm. 13C NMR (75 MHz,
CDCl3): δ = 213.4, 210.5, 195.6, 171.1 (4 C, C=O), 163.7 (arom.
C), 130.5 (2 C, arom. CH), 129.2 (arom. C), 113.7 (2 C, arom. CH),
58.2 [N–C(CH3)3], 55.4 (OCH3), 53.7 (C-3), 48.4, 48.1 (2 C, CH2),
43.4 [C(CH3)3], 39.6, 38.3 (2 C, CH2), 28.1 [3 C, N–C(CH3)3], 26.2
1
ether/hexane). m.p. 135–136 °C. H NMR (300 MHz, CDCl3): δ =
7.91–7.88 (m, 4 H, arom. H), 7.58–7.27 (m, 6 H, arom. H), 4.85
[hep, J = 6.6 Hz, 1 H, N–CH(CH3)2], 3.98 (d, J = 17.2 Hz, 2 H,
Bz–CH2 ϫ2), 3.80 (t, J = 6.6 Hz, 2 H, 6-H), 3.60 (d, J = 17.2 Hz,
2 H, Bz–CH2 ϫ2), 3.14 (t, J = 6.6 Hz, 2 H, 5-H), 1.14 [d, J =
6.6 Hz, 6 H, N–CH(CH3)2] ppm. 13C NMR (75 MHz, CDCl3): δ =
209.8, 197.0, 169.9 (4 C, C=O), 135.9 (2 C, arom. C), 133.5, 128.5,
128.1 (10 C, arom. CH), 52.8 (C-3), 48.8 (2 C, Bz–CH2), 45.0 [N-
CH(CH3)2], 37.6, 36.5 (2 C, C-5, C-6), 19.0 [2 C, N–CH-
[3 C, C(CH ) ] ppm. IR (KBr): ν = 1713, 1678, 1636 (C=O) cm–1.
C24H33NO5 (415.52): calcd. C 69.37, H 8.00, N 3.37; found C
69.22, H 8.15, N 3.30.
˜
(CH ) ] ppm. IR (KBr): ν = 1717, 1693, 1630 (C=O) cm–1.
3 3
˜
3 2
C24H25NO4 (391.46): calcd. C 73.64, H 6.44, N 3.58; found: C 3.35,
H 6.47, N 3.58.
Reaction of 1,3-Dimethyl-5-(2-oxo-2-phenylethyl)barbituric Acid (7):
The barbituric acid 7 was prepared by treatment of 1,3-dimethyl-
barbituric acid (1 mmol) with 2-bromo-1-phenylethanone
(1.5 mmol) at reflux temperature in dry THF (5 mL) in the pres-
ence of sodium hydride (50%, 2.5 mmol) for 40 min. The crude 7
product was separated by TLC on silica gel with elution with 70%
chloroform/diethyl ether, and was further purified by recrystalli-
zation from chloroform/diethyl ether. The obtained 7 (207.5 mg,
0.7566 mmol) was allowed to react with 1a (93.4 mg, 0.518 mmol)
in glacial acetic acid (20 mL) in the presence of manganese(III)
acetate dihydrate (15.0 mg, 0.0559 mmol) at room temperature in
air. After 1a had been consumed (3.5 h), the reaction was quenched
by addition of water (80 mL). The resulting aqueous solution was
extracted with chloroform (3ϫ5 mL), and the combined extracts
were washed with water (50 mL), dried with anhydrous magnesium
sulfate, and concentrated to dryness. The products were separated
by TLC on silica gel with elution with chloroform, and the ob-
tained hydroperoxide 8 was further purified by recrystallization
from chloroform/hexane (235.9 mg, 0.4849 mmol, 94%).
1-Ethyl-3,3-bis(2-oxo-2-phenylethyl)piperidine-2,4-dione (6af): Rf =
0.60 (diethyl ether). Colourless microcrystals (from ethyl acetate/
hexane), m.p. 98.0 °C. 1H NMR (300 MHz, CDCl3): δ = 7.97–7.87
(m, 4 H, arom. H), 7.56–7.38 (m, 6 H, arom. H), 4.00 (d, J =
17.3 Hz, 2 H, Bz–CH2 ϫ2), 3.91 (t, J = 6.6 Hz, 2 H, 6-H), 3.62 (d,
J = 17.3 Hz, 2 H, Bz–CH2 ϫ2), 3.52 (q, J = 7.2 Hz, 2 H, N–
CH2CH3), 3.19 (t, J = 6.6 Hz, 2 H, 5-H), 1.08 (t, J = 7.2 Hz, 3 H,
N–CH2CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 209.6, 196.8,
169.8 (4 C, C=O), 135.5 (2 C, arom. C), 133.4, 128.4, 127.9 (10 C,
arom. CH), 52.2 (C-3), 48.7 (2 C, Bz–CH2), 42.7, 42.6 (2 C, C-6,
N–CH CH ), 37.3 (C-5), 11.7 (N–CH CH ) ppm. IR (KBr): ν =
˜
2
3
2
3
1713, 1686, 1632 (C=O) cm–1. C23H23NO4 (377.43): calcd. C 73.19,
H 6.14, N 3.71; found C 73.11, H 6.17, N 3.73.
3-(3,3-Dimethyl-2-oxobutyl)-3-[2-oxo-2-(naphth-2-yl)ethyl]piper-
idine-2,4-dione (6Јfi): Rf = 0.27 (chloroform/methanol, 98:2, v/v).
1
Colourless needles (from diethyl ether/hexane), m.p. 185 °C. H
NMR (300 MHz, CDCl3): δ = 8.43 (br. s, 1 H, arom. H), 7.95–7.84
(m, 4 H, arom. H), 7.63–7.52 (m, 2 H, arom. H), 6.38 (br. s, 1 H,
NH), 4.02 (d, J = 17.4 Hz, 1 H, CH2), 3.96–3.78 (m, 2 H, 6-H),
3.68 (d, J = 17.4 Hz, 1 H, CH2), 3.56 (d, J = 17.8 Hz, 1 H, CH2),
3.25 (d, J = 17.8 Hz, 1 H, CH2), 3.13 (br. t, J = 6.4 Hz, 2 H, 5-H),
1.13 [s, 9 H, C(CH3)3] ppm. 13C NMR (75 MHz, CDCl3): δ =
213.4, 209.7, 196.8, 173.5 (4 C, C=O), 135.7, 132.9, 132.3 (3 C,
arom. C), 130.2, 129.6, 128.7, 128.5, 127.7, 126.9, 123.5 (7 C, arom.
CH), 52.4 (C-3), 48.9, 47.8 (2 C, CH2), 43.5 [C(CH3)3], 37.4, 36.8
1,3-Dimethyl-5-(2-oxo-2-phenylethyl)barbituric Acid (7): Rf = 0.33
(chloroform/diethyl ether, 7:3, v/v). Colourless prisms (from chloro-
1
form/diethyl ether), m.p. 200.0 °C. H NMR (300 MHz, CDCl3): δ
= 7.94–7.92 (m, 2 H, arom. H), 7.61–7.43 (m, 3 H, arom. H), 4.01
(m, 2 H, Bz–CH2), 3.60 (m, 1 H, 5-H), 3.34 (s, 6 H, CH3 ϫ2) ppm.
13C NMR (75 MHz, CDCl3): δ = 196.8, 167.8, 151.5 (3 C, C=O),
135.0 (arom. C), 133.8, 128.6, 128.1 (5 C, arom. CH), 44.3 (C-5),
37.6 (Bz–CH ), 28.6 (2 C, CH ϫ2) ppm. IR (KBr): ν = 1697, 1660
(2 C, CH ), 26.2 [3 C, C(CH ) ] ppm. IR (KBr): ν = 3221 (NH),
˜
˜
2
3
2
3 3
(C=O) cm–1. C14H14N2O4 (274.27): calcd. C 61.31, H 5.14, N 10.21;
1707, 1684, 1665 (C=O) cm–1. C23H25NO4 (379.45): calcd. C 72.80,
found C 61.24, H 5.26, N 10.12.
H 6.64, N 3.69; found C 72.66, H 6.73, N 3.67.
5-(2-Hydroperoxy-2,2-diphenylethyl)-1,3-dimethyl-5-(2-oxo-2-phen-
ylethyl)barbituric Acid (8): Rf = 0.29 (chloroform). Colourless
microcrystals (from chloroform/hexane), m.p. 232–233 °C. 1H
NMR (300 MHz, CDCl3): δ = 8.64 (br. s, 1 H, OOH), 7.88–7.86
(m, 2 H, arom. H), 7.60–7.21 (m, 13 H, arom. H), 4.07 (s, 2 H, Bz–
CH2), 3.48 (s, 2 H, CH2), 3.00 (s, 6 H, CH3 ϫ2) ppm. 13C NMR
(75 MHz, CDCl3): δ = 196.5, 172.9, 150.5 (3 C, C=O), 142.1, 134.9
(3 C, arom. C), 134.0, 128.7, 128.5, 128.2, 127.5, 125.4 (15 C, arom.
CH), 86.4 (Ph2C), 52.2 (Bz–CH2), 48.9 (C-5), 43.4 (CH2), 28.8 (2
1-Benzyl-3-[2-(4-methoxyphenyl)-2-oxoethyl]-3-(2-oxo-2-phenyl-
ethyl)piperidine-2,4-dione (6eb): Rf = 0.40 (chloroform/methanol,
98:2, v/v). Colourless prisms (from diethyl ether/hexane), m.p. 141–
143 °C. 1H NMR (300 MHz, CDCl3): δ = 7.92–7.88 (m, 4 H, arom.
H), 7.56–7.24 (m, 8 H, arom. H), 6.92–6.89 (m, 2 H, arom. H),
4.72 (d, J = 15.0 Hz, 1 H, Ph–CH2), 4.65 (d, J = 15.0 Hz, 1 H, Ph–
CH2), 4.07 (d, J = 13.0 Hz, 1 H, CH2), 4.01 (d, J = 12.7 Hz, 1 H,
CH2), 3.84 (s, 3 H, OCH3), 3.83 (t, J = 6.6 Hz, 2 H, 6-H), 3.68 (d,
J = 13.0 Hz, 1 H, CH2), 3.62 (d, J = 12.7 Hz, 1 H, CH2), 3.15 (t,
J = 6.6 Hz, 2 H, 5-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 209.7,
197.0, 195.3, 171.1 (4 C, C=O), 163.9, 136.7, 135.8 (3 C, arom. C),
133.6, 130.6 (arom. CH), 128.8 (arom. C), 128.6, 128.5, 128.2,
127.8, 127.2, 113.8 (arom. CH), 55.4 (OCH3), 52.7 (C-3), 50.9 (Ph–
C, CH ϫ2) ppm. IR (KBr): ν = 3600–3200 (OOH), 1672, 1663
˜
3
(C=O) cm–1. C28H26N2O6 (486.52): calcd. C 69.12, H 5.39, N 5.76;
found C 69.12, H 5.52, N 5.81.
Aerobic Oxidation with Cycloalkane-1,3-diones 9a–e and Quinol-
CH2), 49.2, 48.9 (2 C, Bz–CH2, 4-MeO-C6H4-CH2), 42.8 (C-6), inone 12: Cyclohexane-1,3-dione 9 or quinolinone 12 (0.5 mmol)
37.4 (C-5) ppm. IR (KBr): ν 1713, 1684, 1636 (C=O) cm–1
.
was allowed to react with the alkene 1 (0.25 mmol) in the presence
˜
2412
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 2404–2416

Facile Endoperoxypropellane Synthesis
of manganese(III) acetate dihydrate (0.025–0.1 mmol) in glacial
acetic acid (10 mL) in air until the alkene 1 had been consumed
(normally for 0.5–1.5 h). After the reaction, the mixture was heated
at 100 °C for 30 min, and the normal workup was done. The ob-
tained products 10, 11, 13, and 14 were further purified by
recrystallization from the appropriate solvents.
4-Methyl-4,12-diphenyl-2,3,11-trioxatricyclo[4.4.3.01,6]tridec-12-en-
7-one (10ga) (Stereoisomer 1): Rf = 0.56 (chloroform). Colourless
oil. 1H NMR (300 MHz, CDCl3): δ = 7.69–7.66 (m, 2 H, arom.
H), 7.43–7.18 (m, 8 H, arom. H), 5.37 (s, 1 H, 13-H), 2.88 (d, J =
13.9 Hz, 1 H, 5-H), 2.64–2.55 (m, 1 H, CH2), 2.32–2.20 (m, 2 H,
CH2), 2.08 (d, J = 13.9 Hz, 1 H, 5-H), 1.92–1.83 (m, 2 H, CH2),
1.71–1.61 (m, 1 H, CH2), 1.46 (s, 3 H, CH3) ppm. 13C NMR
(75 MHz, CDCl3): δ = 207.8 (C=O), 157.4 (C-12), 147.8 (arom. C),
129.33 (2 C, arom. CH), 129.26 (arom. C), 128.4, 128.3, 126.8,
125.4, 124.0 (8 C, arom. CH), 113.2 (C-1), 98.0 (C-13), 83.2 (C-4),
59.8 (C-6), 36.5, 36.1 (2 C, C-5, C-10), 30.1 (CH3), 28.4 (C-8), 16.2
4,4,12-Triphenyl-2,3,11-trioxatricyclo[4.4.3.01,6]tridec-12-en-7-one
(10aa): Rf = 0.62 (chloroform). Colourless oil. 1H NMR (300 MHz,
CDCl3): δ = 7.51–7.09 (m, 15 H, arom. H), 4.83 (s, 1 H, 13-H),
3.46 (d, J = 14.1 Hz, 1 H, 5-H), 2.61–2.53 (m, 1 H, 10-H), 2.53 (d,
J = 14.1 Hz, 1 H, 5-H), 2.34–2.22 (m, 2 H, 8-H, 10-H), 1.90–1.83
(m, 2 H, 9-H), 1.75 (ddd, J = 13.4, 11.9, 4.4 Hz, 1 H, 8-H) ppm.
13C NMR (75 MHz, CDCl3): δ = 207.7 (C=O), 156.7 (C-12), 146.9,
143.8 (2 C, arom. C), 130.0 (2 C, arom. CH), 129.3 (arom. C),
129.1, 128.3, 128.23, 128.20, 128.15, 127.9, 127.7, 127.1, 126.9,
125.4, 125.3, 125.2, 125.1 (13 C, arom. CH), 113.7 (C-1), 98.6, 98.5
(1 C, C-13), 85.8 (C-4), 59.8 (C-6), 36.4 (C-10), 35.9 (C-5), 28.2 (C-
(C-9) ppm. IR (KBr): ν = 1701 (C=O) cm–1. FAB HRMS (acetone/
˜
NBA): calcd. for C23H22O4 362.1518 (M); found 362.1503.
4-Methyl-4,12-diphenyl-2,3,11-trioxatricyclo[4.4.3.01,6]tridec-12-en-
7-one (10ga) (Stereoisomer 2): Rf = 0.44 (chloroform). Colourless
1
oil. H NMR (300 MHz, CDCl3): δ = 7.56–7.16 (m, 10 H, arom.
H), 4.68 (s, 1 H, 13-H), 2.82 (d, J = 13.9 Hz, 1 H, 5-H), 2.63–2.54
(m, 1 H, CH2), 2.39–2.27 (m, 2 H, CH2), 2.06 (d, J = 13.9 Hz, 1
H, 5-H), 1.99–1.82 (m, 3 H, CH2), 1.68 (s, 3 H, CH3) ppm. 13C
NMR (75 MHz, CDCl3): δ = 207.9 (C=O), 156.7 (C-12), 145.4,
129.4 (2 C, arom. C), 129.1, 128.3, 127.9, 126.6, 125.4, 124.5 (10
C, arom. CH), 113.4 (C-1), 98.6 (C-13), 82.8 (C-4), 59.8 (C-6), 37.5,
36.4 (2 C, C-5, C-10), 30.1 (CH3), 28.4 (C-8), 16.4 (C-9) ppm. IR
8), 16.3 (C-9) ppm. IR (KBr): ν = 1703 (C=O) cm–1. FAB HRMS
˜
(acetone/NBA): calcd. for C28H25O4 425.1753 (M + 1); found
425.1784.
9,9-Dimethyl-4,4,12-triphenyl-2,3,11-trioxatricyclo[4.4.3.01,6]tri-
dec-12-en-7-one (10ab): Rf = 0.67 (chloroform). Colourless micro-
crystals (from diethyl ether/hexane), m.p. 182 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.50–6.95 (m, 15 H, arom. H), 5.05 (s, 1
H, 13-H), 3.30 (d, J = 13.9 Hz, 1 H, 5-H), 2.53 (d, J = 13.9 Hz, 1
H, 5-H), 2.39 (d, J = 15.2 Hz, 1 H, 10-H), 2.23 (br. d, J = 14.8 Hz,
2 H, 8-H, 10-H), 1.76 (d, J = 14.3 Hz, 1 H, 8-H), 1.02 (s, 3 H,
CH3), 0.96 (s, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ =
209.2 (C=O), 155.0 (C-12), 146.9, 143.7, 129.5 (3 C, arom. C),
129.0, 128.3, 128.2, 128.0, 127.1, 127.0, 125.2, 125.0 (15 C, arom.
CH), 114.0 (C-1), 99.6 (C-13), 85.3 (C-4), 58.8 (C-6), 50.6 (C-10),
40.5 (C-5), 36.8 (C-8), 31.5 (CH3), 31.0 (C-9), 27.0 (CH3) ppm. IR
(KBr): ν = 1705 (C=O) cm–1. FAB HRMS (acetone/NBA): calcd.
˜
for C23H23O4 363.1596 (M + 1); found 363.1592.
4,12-Diphenyl-2,3,11-trioxatricyclo[4.4.3.01,6]tridec-12-en-7-one
(10ha): Rf = 0.50 (chloroform). Colourless oil. 1H NMR (300 MHz,
CDCl3): δ = 7.70–7.66 (m, 2 H, arom. H), 7.43–7.27 (m, 8 H, arom.
H), 5.42 (s, 1 H, 13-H), 5.28 (dd, J = 10.6, 7.0 Hz, 1 H, 4-H), 2.79
(dd, J = 13.9, 7.0 Hz, 1 H, 5-H), 2.67–2.58 (m, 1 H, CH2), 2.41–
2.23 (m, 2 H, CH2), 2.01–1.83 (m, 3 H, CH2), 1.97 (dd, J = 13.9,
10.6 Hz, 1 H, 5-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 208.2
(C=O), 158.1 (C-12), 141.8 (arom. C), 129.5 (2 C, arom. CH), 129.1
(arom. C), 128.6, 128.5, 127.8, 125.6, 125.1 (8 C, arom. CH), 113.6
(C-1), 97.1 (C-13), 80.1 (C-4), 59.8 (C-6), 36.6 (C-10), 31.5 (C-5),
(neat): ν = 1711 (C=O) cm–1. C H O (452.54): calcd. C 79.62, H
˜
30 28
4
6.24; found C 79.36, H 6.34.
28.4 (C-8), 16.5 (C-9) ppm. IR (KBr): ν = 1705 (C=O) cm–1. FAB
8,8-Dimethyl-4,4,12-triphenyl-2,3,11-trioxatricyclo[4.4.3.01,6]tri-
dec-12-en-7-one (10ac): Rf = 0.29 (chloroform/hexane, 5:5, v/v).
Colourless microcrystals (from diethyl ether/hexane), m.p. 160–
163 °C. 1H NMR (300 MHz, CDCl3): δ = 7.56–7.00 (m, 15 H,
arom. H), 4.78 (s, 1 H, 13-H), 3.56 (d, J = 14.3 Hz, 1 H, 5-H), 2.46
(d, J = 14.3 Hz, 1 H, 5-H), 2.22–2.67, 1.93–1.80, 1.70–1.61 (m, 4
H, 9-H, 10-H), 1.10 (s, 6 H, CH3 ϫ2) ppm. 13C NMR (75 MHz,
CDCl3): δ = 212.3 (C=O), 156.4 (C-12), 147.0, 143.9, 129.3 (3 C,
arom. C), 129.1, 128.3, 128.2, 127.1, 125.4, 125.3, 125.1 (15 C,
arom. CH), 113.8 (C-1), 99.1 (C-13), 85.8 (C-4), 59.3 (C-6), 42.8
(C-8), 36.9 (C-5), 31.1 (C-10), 28.6, 26.7 (2 C, CH3 ϫ2), 25.9 (C-
˜
HRMS (acetone/NBA): calcd. for C22H21O4 349.1440 (M + 1);
found 349.1425.
4,4-Diethyl-12-phenyl-2,3,11-trioxatricyclo[4.4.3.01,6]tridec-12-en-7-
one (10ia): Rf = 0.49 (chloroform). Colourless oil. 1H NMR
(300 MHz, CDCl3): δ = 7.62–7.60 (m, 2 H, arom. H), 7.40–7.33
(m, 3 H, arom. H), 5.23 (s, 1 H, 13-H), 2.65–2.56 (m, 1 H, CH2),
2.40–2.22 (m, 2 H, CH2), 2.37 (d, J = 14.3 Hz, 1 H, 5-H), 1.96–
1.74 (m, 4 H, CH2), 1.61–1.44 (m, 3 H, CH2), 1.45 (d, J = 14.3 Hz,
1 H, 5-H), 0.85 (t, J = 7.7 Hz, 3 H, CH2CH3), 0.83 (t, J = 7.7 Hz,
3 H, CH2CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 208.5
(C=O), 157.0 (C-12), 129.4 (arom. C), 129.2, 128.4, 125.4 (5 C,
arom. CH), 113.2 (C-1), 98.5 (C-13), 84.6 (C-4), 59.7 (C-6), 36.4
(C-10), 33.1, 29.2, 28.8, 27.3 (4 C, C-5, C-8, CH2CH3), 16.3 (C-9),
9) ppm. IR (KBr): ν = 1697 (C=O) cm–1. C H O (452.54): calcd.
˜
30 28
4
C 79.62, H 6.24; found C 79.48, H 6.30.
12-(Naphth-2-yl)-4,4-diphenyl-2,3,11-trioxatricyclo[4.4.3.01,6]tri-
dec-12-en-7-one (10ad): Rf = 0.51 (chloroform). Colourless micro-
crystals (from diethyl ether/hexane), m.p. 153 °C. 1H NMR
(300 MHz, CDCl3): δ = 8.08–7.70 (m, 5 H, arom. H), 7.56–7.10
(m, 12 H, arom. H), 4.96 (s, 1 H, 13-H), 3.50 (d, J = 14.3 Hz, 1 H,
5-H), 2.64–2.55 (m, 1 H, 10-H), 2.57 (d, J = 14.3 Hz, 1 H, 5-H),
2.36–2.24 (m, 2 H, 8-H, 10-H), 1.96–1.74 (m, 3 H, 8-H, 9-H) ppm.
13C NMR (75 MHz, CDCl3): δ = 207.7 (C=O), 156.8 (C-12), 146.9,
7.52, 7.35 (2 C, CH CH ) ppm. IR (KBr): ν = 1703 (C=O) cm–1.
˜
2
3
FAB HRMS (acetone/NBA): calcd. for C20H25O4 329.1753 (M +
1); found 329.1703.
Methyl 4-[Benzyl(tert-butoxycarbonyl)amino]-7-oxo-12-phenyl-
2,3,11-trioxatricyclo[4.4.3.01,6]tridec-12-ene-4-carboxylate (Stereo-
isomer 1, 10ja): Rf = 0.51 (diethyl ether/hexane 1:1, v/v). Colourless
microcrystals (from diethyl ether/hexane), m.p. 128–129 °C. 1H
143.9, 133.5, 133.0, 130.0 (5 C, arom. C), 128.5, 128.4, 128.2, 128.0, NMR (300 MHz, CDCl3): δ = 7.58–7.55 (m, 2 H, arom. H), 7.34–
127.9, 127.6, 127.1, 126.9, 126.7, 126.5, 125.3, 125.2, 124.8, 122.9 7.17 (m, 8 H, arom. H), 5.35 (s, 1 H, 13-H), 4.78 (d, J = 16.5 Hz,
(17 C, arom. CH), 113.9 (C-1), 99.4 (C-13), 85.9 (C-4), 59.9 (C-6), 1 H, Ph–CH2), 4.70 (d, J = 16.5 Hz, 1 H, Ph–CH2), 3.63 (d, J =
36.6 (C-10), 36.0 (C-5), 28.3 (C-8), 16.3 (C-9) ppm. IR (KBr): ν =
15.0 Hz, 1 H, 5-H), 3.60 (s, 3 H, CO2CH3), 2.60–2.51 (m, 1 H,
CH2), 2.29–2.17 (m, 1 H, CH2), 2.08–2.03 (m, 1 H, CH2), 1.85 (d,
J = 15.0 Hz, 1 H, 5-H), 1.82–1.70 (m, 2 H, CH2), 1.41 [s, 9 H,
˜
1701 (C=O) cm–1. C32H26O4 (474.55): calcd. C 80.99, H 5.52; found
C 80.74, H 5.25.
Eur. J. Org. Chem. 2008, 2404–2416
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2413

K. Asahi, H. Nishino
FULL PAPER
C(CH3)3], 1.36–1.28 (m, 1 H, CH2) ppm. 13C NMR (75 MHz, 29.9 (N–CH ) ppm. IR (KBr): ν = 3500–3150 (OOH), 1682, 1636
˜
3
CDCl3): δ = 206.6 (C=O), 166.6 (C=O), 156.1, 154.3 (2 C, C=O, (C=O) cm–1. C32H27NO5 (505.56): calcd. C 76.02, H 5.38, N 2.77;
C-12), 139.7, 129.3 (2 C, arom. C), 129.2, 128.3, 127.9, 127.2, 126.5, found C 76.04, H 5.26, N 2.83.
125.4 (10 C, arom. CH), 113.0 (C-1), 98.9 (C-13), 93.6 (C-4), 81.8
Reactions with 3-Oxopropyl-Substituted Cyclic 1,3-Diones 15a–f:
[C(CH3)3], 58.8 (C-6), 53.0 (CO2CH3), 47.0 (Ph–CH2), 36.2 (C-8),
1,1-Diphenylethene (1a) (45.1 mg, 0.25 mmol), a 3-oxopropyl-sub-
33.0 (C-10), 28.2 [3 C, C(CH3)3], 28.1 (C-5), 16.0 (C-9) ppm. IR
stituted cyclic 1,3-dione 15 (0.5 mmol), and glacial acetic acid
(KBr): ν = 1763, 1705 (C=O) cm–1. C H NO (535.58): calcd. C
˜
30 33
8
(10 mL) were placed in a 50 mL flask, and manganese(III) acetate
dihydrate (0.025–0.125 mmol) was added to the mixture. The mix-
ture was stirred at room temperature in air until 1a was completely
consumed, followed by rapid quenching with water (80 mL). The
resulting aqueous solution was treated by the workup described
above.
67.28, H 6.21, N 2.62; found C 67.14, H 6.27, N 2.60.
Methyl 4-[Benzyl(tert-butoxycarbonyl)amino]-7-oxo-12-phenyl-
2,3,11-trioxatricyclo[4.4.3.01,6]tridec-12-ene-4-carboxylate (Stereo-
isomer 2, 10ja): Rf = 0.38 (diethyl ether/hexane, 1:1, v/v). Colourless
1
oil. H NMR (300 MHz, CDCl3): δ = 7.99–7.09 (m, 10 H, arom.
H), 5.19 (s, 1 H, 13-H), 4.54 (d, J = 16.5 Hz, 1 H, Ph–CH2), 4.46
(d, J = 16.5 Hz, 1 H, Ph–CH2), 3.74 (s, 3 H, CO2CH3), 3.04 (d, J =
15.0 Hz, 1 H, 5-H), 2.63–2.54 (m, 1 H, CH2), 2.57 (d, J = 15.0 Hz, 1
H, 5-H), 2.49–2.37 (m, 1 H, CH2), 2.27–2.22 (m, 1 H, CH2), 2.06–
1.87 (m, 3 H, CH2), 1.35 [s, 9 H, C(CH3)3] ppm. 13C NMR
(75 MHz, CDCl3): δ = 206.9 (C=O), 169.2 (C=O), 157.2, 154.1 (2
C, C=O, C-12), 138.7 (2 C, arom. C), 129.7, 128.5, 127.9, 127.1,
126.6, 125.5 (10 C, arom. CH), 113.3 (C-1), 99.2 (C-13), 91.4 (C-
4), 82.4 [C(CH3)3], 58.8 (C-6), 52.8 (CO2CH3), 46.7 (Ph–CH2), 36.7
(C-8), 32.6 (C-10), 29.3 (C-5), 28.0 [3 C, C(CH3)3], 16.3 (C-9) ppm.
1-Hydroxy-6-(3-oxo-3-phenylpropyl)-4,4-diphenyl-2,3-dioxabicyclo-
[4.3.0]nonan-7-one (16a): Rf = 0.31 (chloroform/methanol, 98:2,
v/v). Colourless microcrystals (from ethyl acetate), m.p. 137 °C. 1H
NMR (300 MHz, CDCl3): δ = 7.95–7.92 (m, 2 H, arom. H), 7.53–
7.16 (m, 13 H, arom. H), 4.79 (br. s, 1 H, OH), 3.34 (d, J = 13.9 Hz,
1 H, 5-H), 3.18–3.05 (m, 2 H, Bz–CH2CH2), 2.40 (d, J = 13.9 Hz,
1 H, 5-H), 2.32–1.67 (m, 6 H, 8-H, 9-H, Bz–CH2CH2) ppm. 13C
NMR (75 MHz, CDCl3): δ = 215.4, 199.7 (2 C, C=O), 144.0, 140.0,
136.4 (3 C, arom. C), 133.2, 128.5, 128.3, 128.1, 127.7, 127.6, 127.3,
127.1, 125.3 (15 C, arom. CH), 106.4 (C-1), 85.1 (C-4), 50.7 (C-6),
35.2, 34.7, 31.7, 29.7, 28.2 (5 C, C-5, C-8, C-9, Bz–CH2CH2) ppm.
IR (KBr): ν = 1753, 1709 (C=O) cm–1. FAB HRMS (acetone/
˜
IR (KBr): ν = 3600 –3100 (OH), 1738, 1686 (C=O) cm–1. C H O
NBA): calcd. for C30H33NO8 536.2284 (M + 1); found 536.2384.
˜
28 26
5
4,4-Diphenyl-2,3,11-trioxatricyclo[4.4.3.01,6]tridecane-7,12-dione
(11): Rf = 0.42 (chloroform/methanol, 98:2, v/v). Colourless micro-
crystals (from chloroform/hexane), m.p. 218–219 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.44–7.20 (m, 10 H, arom. H), 3.17 (d, J
= 14.3 Hz, 1 H, 5-H), 2.91 (d, J = 19.0 Hz, 1 H, 13-H), 2.75 (d, J
= 19.0 Hz, 1 H, 13-H), 2.66 (d, J = 14.3 Hz, 1 H, 5-H), 2.54 (br. t, J
= 6.4 Hz, 2 H, CH2), 2.23–1.71 (m, 4 H, CH2 ϫ2) ppm. 13C NMR
(75 MHz, CDCl3): δ = 208.0, 172.9 (2 C, C=O), 145.7, 142.5 (2 C,
arom. C), 129.1, 128.6, 128.0, 127.4, 124.8, 124.6 (10 C, arom. CH),
111.9 (C-1), 85.2 (C-4), 53.5 (C-6), 37.1, 37.0, 34.3, 28.7, 16.9 (5 C,
(442.50): calcd. C 76.00, H 5.92; found C 76.20, H 6.03.
1-Hydroxy-6-(3-oxo-3-phenylpropyl)-4,4-diphenyl-2,3-dioxabicyclo-
[4.4.0]decan-7-one (16b): Rf = 0.31 (chloroform/methanol, 98:2,
v/v). Colourless prisms (from ethyl acetate), m.p. 137–138 °C. 1H
NMR (300 MHz, CDCl3): δ = 7.93–7.90 (m, 2 H, arom. H), 7.54–
7.13 (m, 13 H, arom. H), 4.22 (br. s, 1 H, OH), 3.60 (d, J = 13.6 Hz,
1 H, 5-H), 3.06–2.95 (m, 1 H, Bz–CH2CH2), 2.81–2.70 (m, 1 H,
Bz–CH2CH2), 2.45 (d, J = 13.6 Hz, 1 H, 5-H), 2.34–2.11 (m, 4 H,
8-H, 10-H), 1.99–1.90 (m, 2 H, Bz–CH2CH2), 1.59–1.51 (m, 2 H,
9-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 208.5, 199.2 (2 C,
C=O), 143.8, 141.2, 136.5 (3 C, arom. C), 133.1, 128.5, 128.3,
128.0, 127.2, 126.6, 125.7 (15 C, arom. CH), 101.5 (C-1), 85.3 (C-
4), 53.3 (C-6), 36.6, 33.8, 32.1, 31.1, 29.6 (5 C, C-5, C-8, C-10, Bz–
CH ) ppm. IR (KBr): ν = 1794, 1719 (C=O) cm–1. C22H20O5·
˜
2
1/5H2O (367.99): calcd. C 71.80, H 5.59; found C 71.76, H 5.61.
8-Methyl-4,4,12-triphenyl-2,3,11-trioxa-8-aza-9,10-benzotricyclo-
[4.4.3.01,6]tridec-12-en-7-one (13): Rf = 0.38 (chloroform). Colour-
less microcrystals (from diethyl ether/hexane), m.p. 174–175 °C. 1H
NMR (300 MHz, CDCl3): δ = 7.85–7.78 (m, 2 H, arom. H), 7.47–
7.12 (m, 15 H, arom. H), 7.00–6.97 (m, 2 H, arom. H), 5.29 (s, 1
H, 13-H), 3.61 (d, J = 13.9 Hz, 1 H, 5-H), 3.32 (s, 3 H, N–CH3),
2.81 (d, J = 13.9 Hz, 1 H, 5-H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 168.1 (C=O), 155.4 (C-12), 146.2, 143.5, 137.4 (3 C, arom. C),
132.4, 131.7, 130.0 (arom. CH), 129.09 (arom. C), 129.06, 128.3,
128.2, 128.1, 127.1, 125.5, 125.4, 125.2, 123.8 (arom. CH), 117.6
(arom. C), 114.5 (arom. CH), 108.7 (C-1), 99.3 (C-13), 85.6 (C-4),
CH CH ), 17.2 (C-9) ppm. IR (KBr): ν = 3600–3100 (OH), 1707,
˜
2
2
1684 (C=O) cm–1. C29H28O5·3/5H2O (467.34): calcd. C 74.55, H
6.26; found C 74.78, H 6.55.
6-[3-(4-Chlorophenyl)-3-oxopropyl]-1-hydroxy-4,4-diphenyl-2,3-di-
oxabicyclo[4.4.0]decan-7-one (16c): Rf = 0.11 (chloroform). Colour-
less microcrystals (from ethyl acetate/hexane), m.p. 158 °C. 1H
NMR (300 MHz, CDCl3): δ = 7.88–7.85 (m, 2 H, arom. H), 7.54–
7.16 (m, 12 H, arom. H), 3.92 (br. s, 1 H, OH), 3.61 (d, J = 13.6 Hz,
1 H, 5-H), 3.00–2.92 (m, 1 H, 4-Cl-C6H4-CH2CH2), 2.81–2.73 (m,
1 H, 4-Cl-C6H4-CH2CH2), 2.44 (d, J = 13.6 Hz, 1 H, 5-H), 2.33–
2.13 (m, 4 H, 8-H, 10-H), 2.04–1.91 (m, 2 H, 4-Cl-C6H4-CH2CH2),
1.65–1.55 (m, 2 H, 9-H) ppm. 13C NMR (75 MHz, CDCl3): δ =
208.6, 197.9 (2 C, C=O), 143.8, 141.1, 139.6, 134.9 (4 C, arom. C),
129.5, 128.9, 128.0, 127.4, 127.3, 126.8, 125.8 (14 C, arom. CH),
101.6 (C-1), 85.5 (C-4), 53.3 (C-6), 36.6, 34.0, 32.2, 31.2, 29.6 (5 C,
54.2 (C-6), 37.7 (C-5), 29.7 (N–CH ) ppm. IR (KBr): ν = 1666
˜
3
(C=O) cm–1. C32H25NO4 (487.55): calcd. C 78.83, H 5.17, N 2.87;
found C 78.83, H 5.20, N 2.85.
3-(2-Hydroperoxy-2,2-diphenylethyl)-1-methyl-3-(2-oxo-2-phenyl-
ethyl)-1H-quinoline-2,4-dione (14): Rf = 0.13 (chloroform). Colour-
less microcrystals (from ethyl acetate/hexane), m.p. 174–175 °C. 1H
NMR (300 MHz, CDCl3) δ = 8.91 (br. s, 1 H, OOH), 7.85–7.83
(m, 2 H, arom. H), 7.59–6.90 (m, 17 H, arom. H), 4.24 (s, 2 H,
CH2), 3.58 (d, J = 14.5 Hz, 1 H, Bz–CH2), 3.49 (d, J = 14.5 Hz, 1
C-5, C-8, C-10, 4-Cl-C H -CH CH ), 17.2 (C-9) ppm. IR (KBr): ν
˜
6
4
2
2
= 3600–3150 (OH), 1707, 1686 (C=O) cm–1. C29H27ClO5 (490.97):
calcd. C 70.94, H 5.54; found C 70.70, H 5.51.
Ethyl 3-(1-Hydroxy-7-oxo-4,4-diphenyl-2,3-dioxabicyclo[4.4.0]-
H, Bz–CH2), 3.26 (s, 3 H, N–CH3) ppm. 13C NMR (75 MHz, decan-6-yl)propionate (16d): Rf = 0.33 (chloroform/methanol,
1
CDCl3) δ = 197.6, 196.9, 174.5 (3 C, C=O), 142.8, 141.7 (3 C, arom.
98:2, v/v). Colourless oil. H NMR (300 MHz, CDCl3): δ = 7.51–
C), 135.4 (arom. CH), 135.2 (arom. C), 133.7, 130.8, 128.6, 128.4, 7.13 (m, 10 H, arom. H), 4.07 (q, J = 7.1 Hz, 2 H, O–CH2CH3),
128.34, 128.28, 128.0, 127.6, 127.3, 127.2, 127.1, 125.8, 125.7, 3.52 (d, J = 13.5 Hz, 1 H, 5-H), 2.37 (d, J = 13.5 Hz, 1 H, 5-H),
125.5, 125.4, 123.6, 122.6 (arom. CH), 121.7 (arom. C), 114.6
(arom. CH), 86.5 (Ph2ϾC), 55.0 (CH2), 53.2 (C-3), 46.1 (Bz–CH2),
2.34–1.90 (m, 9 H, OH, CH2 ϫ4), 1.59–1.55 (m, 2 H, 9-H), 1.22 (t,
J = 7.1 Hz, 3 H, O–CH2CH3) ppm. 13C NMR (75 MHz, CDCl3):
2414
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 2404–2416

Facile Endoperoxypropellane Synthesis
δ = 207.9, 173.1 (2 C, C=O), 143.8, 141.1 (2 C, arom. C), 128.2,
127.8, 127.23, 127.19, 126.6, 125.6 (10 C, arom. CH), 101.3 (C-1),
85.3 (C-4), 60.6 (O-CH2CH3), 53.1 (C-6), 36.5, 33.7, 31.1, 30.6,
2-(2-Oxo-2-phenylethyl)-2-(3-oxo-3-phenylpropyl)cyclohexane-1,3-di-
one (17b): Rf = 0.49 (diethyl ether/hexane 8:2, v/v). Colourless
microcrystals (from diethyl ether/hexane), m.p. 102 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.95–7.90 (m, 4 H, arom. H), 7.60–7.41
(m, 6 H, arom. H), 3.83 (s, 2 H, Bz–CH2), 3.04 (t, J = 7.3 Hz, 2
H, Bz–CH2CH2), 2.90–2.76 (m, 4 H, 4-H, 6-H), 2.44–2.31 (m, 1
H, 5-H), 2.28–2.16 (m, 1 H, 5-H), 2.23 (t, J = 7.3 Hz, 2 H, Bz–
CH2CH2) ppm. 13C NMR (75 MHz, CDCl3): δ = 210.1 (2 C,
C=O), 198.1, 197.7 (2 C, C=O), 136.4, 135.7 (2 C, arom. C), 133.6,
133.4, 128.7, 128.6, 128.3, 128.0 (10 C, arom. CH), 63.4 (C-2), 43.4,
38.0, 33.1, 29.1 (5 C, Bz–CH2, C-4, C-6, Bz–CH2CH2), 17.6 (C-
28.2, 17.1 (6 C, CH ), 14.1 (O–CH CH ) ppm. IR (KBr): ν = 3600–
˜
2
2
3
3200 (OH), 1732, 1713 (C=O) cm–1. FAB HRMS (acetone/NBA):
calcd. for C25H29O6 425.1964 (M + 1); found 425.1933.
4a-Hydroxy-9-methyl-10a-(3-oxo-3-phenylpropyl)-2,2-diphenyl-
1,4a,9,10a-tetrahydro-2H-9-aza-3,4-dioxaphenanthren-10-one (16e):
Rf = 0.44 (chloroform/methanol, 98:2, v/v). Colourless microcrys-
1
tals (from methanol), m.p. 161–164 °C. H NMR (300 MHz, [D6]-
DMSO): δ = 7.86–6.97 (m, 19 H, arom. H), 3.75 (d, J = 13.4 Hz,
1 H, 1-H), 3.35 (br. s, 1 H, OH), 2.97–2.82 (m, 2 H, Bz–CH2CH2),
2.78 (d, J = 13.4 Hz, 1 H, 1-H), 2.67 (s, 3 H, N–CH3), 2.02–1.92
5) ppm. IR (KBr): ν = 1720, 1686 (C=O) cm–1. C H O (362.42):
˜
23 22
4
calcd. C 76.22, H 6.12; found C 76.20, H 5.98.
(m, 1 H, Bz–CH2CH2), 1.83–1.74 (m, 1 H, Bz–CH2CH2) ppm. 13C 4,4,9-Triphenyl-2,3,10-trioxatricyclo[4.4.3.01,6]tridec-8-en-13-one
NMR (75 MHz, [D6]DMSO): δ = 198.9, 168.5 (2 C, C=O), 144.6, (18a): Rf = 0.53 (chloroform). Colourless needles (from chloroform/
141.8, 138.5, 136.4 (4 C, arom. C), 133.0, 130.9, 128.5, 128.1,
127.53, 127.45, 127.2, 126.6, 126.5, 125.9, 125.6, 122.6 (12 C, arom.
diethyl ether), m.p. 201 °C. 1H NMR (300 MHz, CDCl3): δ = 7.73–
7.69 (m, 2 H, arom. H), 7.56–7.52 (m, 2 H, arom. H), 7.44–7.13
CH), 122.3 (arom. C), 114.1 (arom. CH), 97.8 (C-4a), 84.5 (C-2), (m, 11 H, arom. H), 5.34 (dd, J = 6.1, 2.6 Hz, 1 H, 8-H), 3.29 (d,
46.5 (C-10a), 35.1 (C-1), 32.4 (Bz–CH2CH2), 29.3 (Bz–CH2CH2), J = 14.1 Hz, 1 H, 5-H), 2.49 (d, J = 14.1 Hz, 1 H, 5-H), 2.31–2.09
29.2 (N–CH ) ppm. IR: ν = 3500–3000 (OH), 1686, 1651 (m, 5 H, 7-H, 11-H, 12-H), 1.82–1.70 (m, 1 H, 11-H) ppm. 13C
˜
3
(C=O) cm–1. C33H29NO5·2/5H2O (526.80): calcd. C 75.26, H 5.66,
N 2.66; found C 75.54, H 5.72, N 2.63.
NMR (75 MHz, CDCl3): δ = 213.9 (C=O), 150.9, 143.8, 139.7,
134.3 (4 C, arom. C, C-9), 128.6, 128.3, 128.2, 128.1, 128.0, 127.9,
127.8, 127.7, 127.3, 125.7, 125.6, 124.8 (15 C, arom. CH), 106.9 (C-
1), 91.8 (C-8), 85.5 (C-4), 43.6 (C-6), 35.1, 34.2, 29.9, 28.8 (4 C, C-5,
2-(2-Oxo-2-phenylethyl)-2-(3-oxo-3-phenylpropyl)cyclopentane-1,3-
dione (17a): Rf = 0.47 (chloroform/methanol, 98:2, v/v). Colourless
C-7, C-11, C-12) ppm. IR (KBr): ν = 1744 (C=O) cm–1. C H O
˜
28 24
4
1
needles (from diethyl ether/hexane), m.p. 153–154 °C. H NMR
(424.49): calcd. C 79.22, H 5.70; found C 79.12, H 5.62.
(300 MHz, CDCl3): δ = 7.95–7.93 (m, 1 H, arom. H), 7.89–7.86
(br. d, J = 8.6 Hz, 1 H, arom. H), 7.60–7.41 (m, 6 H, arom. H),
3.78 (s, 2 H, Bz–CH2), 3.11 (t, J = 7.3 Hz, 2 H, Bz–CH2CH2), 3.06–
4,4,9-Triphenyl-2,3,10-trioxatricyclo[4.4.4.01,6]tetradec-8-en-14-one
(18b): Rf = 0.76 (chloroform). Colourless microcrystals (from di-
2.95 (m, 4 H, 4-H, 5-H), 2.06 (t, J = 7.3 Hz, 2 H, Bz– ethyl ether/hexane), m.p. 161–162 °C. 1H NMR (300 MHz,
CH2CH2) ppm. 13C NMR (75 MHz, CDCl3): δ = 215.8 (2 C,
CDCl3): δ = 7.69–7.66 (m, 2 H, arom. H), 7.57–7.55 (m, 2 H, arom.
H), 7.39–7.13 (m, 11 H, arom. H), 5.26 (dd, J = 5.3, 2.8 Hz, 1 H,
C=O), 198.0, 197.3 (2 C, C=O), 136.3, 134.8 (2 C, arom. C), 134.0,
133.4, 128.7, 128.4, 128.0 (10 C, arom. CH), 55.1 (C-2), 45.6 (Bz– 8-H), 3.44 (d, J = 13.8 Hz, 1 H, 5-H), 2.65 (d, J = 13.8 Hz, 1 H,
CH2), 35.2 (2 C, C-4, C-5), 32.3 (Bz–CH2CH2), 26.6 (Bz– 5-H), 2.43 (dd, J = 18.4, 2.8 Hz, 1 H, 7-H), 2.25–2.11, 1.93–1.84
CH CH ) ppm. IR (KBr): ν = 1720, 1684 (C=O) cm–1. C H O
(348.39): calcd. C 75.84, H 5.79; found C 75.79, H 5.76.
(m, 4 H, 7-H, 11-H, 13-H), 1.78–1.64 (m, 2 H, 12-H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 209.7 (C=O), 149.5, 143.3, 140.7,
134.5 (4 C, arom. C, C-9), 130.1, 128.6, 128.43, 128.37, 128.33,
128.27, 128.0, 127.9, 127.6, 127.1, 126.2, 124.7 (15 C, arom. CH),
102.6 (C-1), 91.7 (C-8), 85.6 (C-4), 46.4 (C-6), 35.7 (C-5), 35.3 (C-
13), 32.29, 32.26, 32.2 (1 C, C-7), 29.4 (C-11), 16.4 (C-12) ppm. IR
˜
2
2
22 20
4
3-(2-Oxo-2-phenylethyl)-3-(3-oxo-3-phenylpropyl)chroman-2,4-dione
(17f): Rf = 0.56 (chloroform/methanol, 98:2, v/v). Colourless oil.
1H NMR (300 MHz, CDCl3): δ = 7.97–7.26 (m, 14 H, arom. H),
4.23 (d, J = 17.8 Hz, 1 H, Bz–CH2), 4.05 (d, J = 17.8 Hz, 1 H, Bz–
CH2), 3.19–3.00 (m, 2 H, Bz–CH2CH2), 2.50–2.32 (m, 2 H, Bz–
CH2CH2) ppm. 13C NMR (75 MHz, CDCl3): δ = 197.2 (2 C,
C=O), 193.0, 170.5 (2 C, C=O), 154.6 (C-6), 136.9 (arom. CH),
(KBr): ν = 1711 (C=O) cm–1. C H O (438.51): calcd. C 79.43,
˜
29 26
4
H 5.98; found C 79.35, H 5.85.
9-(4-Chlorophenyl)-4,4-diphenyl-2,3,10-trioxatricyclo[4.4.4.01,6]-
136.0 (arom. C), 134.9 (arom. CH), 133.9 (arom. C), 133.3, 128.5, tetradec-8-en-14-one (18c): Rf = 0.53 (chloroform). Colourless
128.3, 127.8, 127.33, 127.28, 125.0 (arom. CH), 118.1 (arom. C),
117.6 (arom. CH), 56.0 (C-3), 45.7 (Bz–CH2), 32.8 (Bz–CH2CH2),
needles (from diethyl ether/hexane), m.p. 170 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.60–7.54 (m, 4 H, arom. H), 7.34–7.14
(m, 10 H, arom. H), 5.24 (dd, J = 5.1, 2.6 Hz, 1 H, 8-H), 3.69 (d,
J = 13.8 Hz, 1 H, 5-H), 2.62 (d, J = 13.8 Hz, 1 H, 5-H), 2.41 (dd,
J = 18.4, 2.6 Hz, 1 H, 7-H), 2.24–1.84, 1.93–1.84 (m, 5 H, 7-H,
11-H, 13-H), 1.76–1.60 (m, 2 H, 12-H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 209.5 (C=O), 148.6, 143.2, 140.6, 134.2, 132.9 (5 C,
arom. C, C-9), 132.4, 130.1, 128.4, 128.3, 128.0, 127.9, 127.6, 127.1,
126.1, 126.0 (14 C, arom. CH), 102.7 (C-1), 92.2 (C-8), 85.6 (C-4),
46.3 (C-6), 35.7 (C-5), 35.3 (C-13), 32.1 (C-7), 29.4 (C-11), 16.3 (C-
30.7 (Bz–CH CH ) ppm. IR (KBr): ν = 1767, 1686 (C=O) cm–1.
˜
2
2
FAB HRMS (acetone/NBA): calcd. for C26H21O5 413.1386 (M +
1); found 413.1376.
Cyclization of 3-Oxopropyl-Substituted Bicyclic Endoperoxides 16 in
the Presence of a Lewis Acid: The 3-oxopropyl-substituted bicyclic
endoperoxides 16a–c or 16e (0.1 mmol) and dry solvent (2 mL)
were placed in a 30 mL flask, and the Lewis acid was added to the
mixture. The mixture was then stirred under the conditions de-
scribed in Table 5. The resulting solution was quenched with water
(10 mL) and the aqueous solution was extracted with chloroform
(3ϫ5 mL). The combined chloroform extracts were dried with an-
hydrous magnesium sulfate and concentrated to dryness. The ob-
tained crude products were separated by TLC on silica gel with
elution with chloroform, giving the corresponding propellanes 18a–
c or 19. In some cases, the acid decomposition product 17b was
also produced. The obtained products were further purified by
recrystallization from appropriate solvents.
12) ppm. IR (KBr): ν = 1709 (C=O) cm–1. C H ClO (472.96):
˜
29 25
4
calcd. C 73.64, H 5.33; found C 73.60, H 5.38.
8-Methyl-3,12,12-triphenyl-2,11-dioxa-8-aza-9,10-benzotricyclo-
[4.4.3.01,6]tridec-3-en-7-one (19):[15] Rf = 0.31 (chloroform). Colour-
less prisms (from diethyl ether/hexane), m.p. 209 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.77–7.01 (m, 19 H, arom. H), 5.21 (dd, J
= 5.3, 2.4 Hz, 1 H, 4-H), 3.78 (d, J = 12.5 Hz, 1 H, 13-H), 3.14 (d,
J = 12.5 Hz, 1 H, 13-H), 3.07 (s, 3 H, N–CH3), 2.56 (dd, J = 18.5,
5.3 Hz, 1 H, 5-H), 2.15 (dd, J = 18.5, 2.4 Hz, 1 H, 5-H) ppm. 13C
Eur. J. Org. Chem. 2008, 2404–2416
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2415

K. Asahi, H. Nishino
FULL PAPER
[7] H. Nishino, in Bioactive Heterocycles I (Ed.: S. Eguchi),
Springer, Berlin, 2006, pp. 39–76.
[8] a) A. Rabert, O. Dechy-Cabaret, J. Cazelles, B. Meunier, Acc.
Chem. Res. 2002, 35, 167–174; b) G. H. Posner, P. M. O’Neill,
Acc. Chem. Res. 2004, 37, 397–404.
NMR (75 MHz, CDCl3): δ = 170.6 (C=O), 147.8, 147.6, 145.4,
138.2, 134.3 (5 C, 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 (1 C, C-4), 88.5 (C-
12), 50.0 (C-6), 45.2 (C-13), 29.7 (N–CH3), 26.3 (C-5) ppm. IR
[9] a) A. Walser, C. Djerassi, Helv. Chim. Acta 1965, 48, 391–404;
b) K. Awang, T. Sevenet, A. H. A. Hadi, B. David, M. Païs,
Tetrahedron Lett. 1992, 33, 2493–2496; c) K. Wiesner, I. Jir-
kowsk, M. Fishman, C. A. J. Williams, Tetrahedron Lett. 1967,
1523–1526; d) T. Ibuka, K. Tanaka, Y. Inubushi, Tetrahedron
Lett. 1972, 1392–1396; e) M. Kurosu, L. R. Marcin, T. J.
Grinsteiner, Y. Kishi, J. Am. Chem. Soc. 1998, 120, 6627–6628.
[10] K. Asahi, H. Nishino, Heterocycl. Commun. 2007, in press.
[11] a) C.-Y. Qian, J. Hirose, H. Nishino, K. Kurosawa, J. Hetero-
cycl. Chem. 1994, 31, 1219–1227; b) V.-H. Nguyen, H. Nishino,
K. Kurosawa, Tetrahedron Lett. 1997, 38, 1773–1776; c) V.-H.
Nguyen, H. Nishino, K. Kurosawa, Heterocycles 1998, 48, 465–
480; d) F. A. Chowdhury, H. Nishino, K. Kurosawa, Heterocy-
cles 1999, 51, 575–591.
(KBr): ν = 1672 (C=O) cm–1. C H NO (485.57): calcd. C 81.63,
˜
33 27
3
H 5.60, N 2.88; found C 81.64, H 5.73, N 2.92.
Supporting Information (see also the footnote on the first page of
this article): 1H NMR, 13C NMR, DEPT, and IR spectra of trioxa-
azapropellanes 4ab, 4ah (9 pages), and the equilibrium mixture 5aa,
5eb, 5ei, and 5fi (16 pages).
Acknowledgments
This research was supported by the Japanese Society for the Pro-
motion of Science (Grants-in-Aid for Scientific Research (C),
No. 15550039 and No. 19550046). We gratefully acknowledge Pro-
fessor Teruo Shinmyozu, Institute for Materials Chemistry and
Engineering, Kyushu University, Japan, for the measurement of the
high-resolution FAB mass spectrum.
[12] The N-tert-butyl substituent in the corresponding rearrange-
ment product 6fi was removed under the acid conditions to
produce 6Јfi.
[13] C.-Y. Qian, H. Nishino, K. Kurosawa, J. D. Korp, J. Org.
Chem. 1993, 58, 4448–4451.
[14] a) M. T. Rahman, H. Nishino, C.-Y. Qian, Tetrahedron Lett.
2003, 44, 5225–5228; b) M. T. Rahman, H. Nishino, Tetrahe-
dron 2003, 59, 8383–8392; c) M. T. Rahman, H. Nishino, Org.
Lett. 2003, 5, 2887–2890.
[15] a) B. B. Snider, Chem. Rev. 1996, 96, 339–363; b) H. Nishino,
V.-H. Nguyen, S. Yoshinaga, K. Kurosawa, J. Org. Chem. 1996,
61, 8264–8271.
[16] a) H. Nishino, Bull. Chem. Soc. Jpn. 1985, 58, 1922–1927; b)
S. Tategami, T. Yamada, H. Nishino, J. D. Korp, K. Kurosawa,
Tetrahedron Lett. 1990, 31, 6371–6374; c) H. Nishino, S. Tate-
gami, T. Yamada, J. D. Korp, K. Kurosawa, Bull. Chem. Soc.
Jpn. 1991, 64, 1800–1809; d) M. I. Colombo, S. Signorella,
M. P. Mischne, M. Gonzalez-Sierra, E. A. Ruveda, Tetrahedron
1990, 46, 4149–4154; e) F. A. Chowdhury, H. Nishino, K. Ku-
rosawa, Tetrahedron Lett. 1998, 39, 7931–7934; f) R. Kumabe,
H. Nishino, M. Yasutake, V.-H. Nguyen, K. Kurosawa, Tetra-
hedron Lett. 2001, 42, 69–72; g) R. Kumabe, H. Nishino, Heter-
ocycl. Commun. 2005, 10, 135–138; h) R. Fujino, H. Nishino,
Synthesis 2005, 731–740.
[1] A. J. Pihko, A. M. P. Koskinen, Tetrahedron 2005, 61, 8769–
8807.
[2] a) J. J. Dugan, P. de Mayo, M. Nisbet, J. R. Robinson, M. J.
Anchel, J. Am. Chem. Soc. 1966, 88, 2838–2844; b) M. Konishi,
H. Ohkuma, T. Tsuno, T. Oki, J. Am. Chem. Soc. 1990, 112,
3715–3716; c) E. Haslam, Shikimic Acid Metabolism and Me-
tabolites, John Wiley & Sons, New York, 1993; d) G. A. Elles-
tad, M. P. Kunstmann, H. A. Whaley, E. L. Patterson, J. Am.
Chem. Soc. 1968, 90, 1325–1332; e) J. Qian-Cutrone, Q. Gao,
S. Huang, S. E. Klohr, J. A. Veitch, Y.-Z. Shu, J. Nat. Prod.
1994, 57, 1656–1660; f) K. Okabe, K. Yamada, D. Yamamura,
S. Takeda, J. Chem. Soc. C 1967, 2201–2206; g) K. Nakanishi,
Pure Appl. Chem. 1967, 14, 89–113.
[3] a) W. J. Greenlee, R. B. Woodward, J. Am. Chem. Soc. 1976,
98, 6075–6076; b) R. K. Boeckman, S. S. Ko, J. Am. Chem.
Soc. 1980, 102, 7146–7149; c) A. Ichihara, M. Ubukata, H.
Oikawa, K. Murakami, S. Sakamura, Tetrahedron Lett. 1980,
21, 4469–4472; d) J. Taunton, J. L. Wood, S. L. Schreiber, J.
Am. Chem. Soc. 1993, 115, 10378–10379; e) A. G. Myers, N. J. [17] a) C. M. Thompson, J. A. Frick, D. L. C. Green, J. Org. Chem.
Tom, M. E. Fraley, S. B. Cohen, D. J. Madar, J. Am. Chem.
Soc. 1997, 119, 6072–6094; f) M. D. Shair, T. Y. Yoon, K. K.
Mosny, T. C. Chou, S. J. Danishefsky, J. Am. Chem. Soc. 1996,
118, 9509–9525; g) M. Uchiyama, Y. Kimura, A. Ohta, Tetra-
hedron Lett. 2000, 41, 10013–10017; h) E. J. Corey, M. Kang,
M. C. Desai, A. K. Ghosh, I. N. Houpis, J. Am. Chem. Soc.
1988, 110, 649–651; i) M. T. Crimmins, J. M. Pace, P. G. Nan-
termet, A. S. Kim-Meade, J. B. Thomas, S. H. Watterson, A. S.
Wagman, J. Am. Chem. Soc. 2000, 122, 8453–8463.
1990, 55, 111–116; b) X. Qi, X. Wang, L. Wang, Q. Wang, S.
Cheng, J. Suo, J. Chang, Eur. J. Med. Chem. 2005, 40, 805–
810; c) R. J. Cherney, L. Wang, J. Org. Chem. 1996, 61, 2544–
2546.
[18] a) N. P. Maini, P. M. Sammes, J. Chem. Soc., Perkin Trans. 1
1988, 161–168; b) C. M. Pirrung, G. J. N. Webster, J. Org.
Chem. 1987, 52, 3603–3613; c) H. Stetter, Angew. Chem. 1995,
67, 769–788; d) N. R. Naik, A. F. Amin, S. R. Patel, J. Indian
Chem. Soc. 1979, 56, 708–711; e) D. R. Buckle, B. C. C. Can-
tello, H. Smith, B. A. Spicer, J. Med. Chem. 1975, 18, 726–732.
[19] a) S. Miyano, D.-L. L. Lu, M. S. Viti, K. B. Sharpless, J. Org.
Chem. 1985, 50, 4350–4360; b) J.-C. Zhou, K. Schenk, Helv.
Chim. Acta 2002, 85, 1276–1283; c) J.-C. Jung, Y.-J. Jung, O.-
S. Park, Synth. Commun. 2001, 31, 1195–1200; d) P. Bravo, C.
Ticozzi, G. Cavicchio, Synthesis 1985, 9, 894–896; e) M.
Kannno, T. Nakae, S. Sakuyama, K. Imaki, H. Nakai, N.
Hamanaka, Synlett 1997, 12, 1472–1474.
[4] a) K. B. Wiberg, Chem. Rev. 1989, 89, 975–983; b) K. B. Wib-
erg, S. T. Waddell, J. Am. Chem. Soc. 1990, 112, 2194–2216; c)
P. E. Eaton, G. H. Temme III, J. Am. Chem. Soc. 1973, 95,
7508–7510.
[5] a) K. Asahi, H. Nishino, Tetrahedron Lett. 2006, 47, 7259–
7262; b) K. Asahi, H. Nishino, Tetrahedron 2007, 63, in press.
[6] a) R. Kumabe, H. Nishino, Tetrahedron Lett. 2004, 45, 703–
706; b) K. Asahi, H. Nishino, Heterocycl. Commun. 2005, 11,
379–384; c) K. Asahi, H. Nishino, Tetrahedron 2005, 61,
11107–11124.
Received: December 30, 2007
Published Online: March 25, 2008
2416
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 2404–2416