Synthesis of small ring-containing conjugated dienes via the coupling reaction of cyclopropyl- and cyclobutylmagnesium carbenoids with α-sulfonylallyllithiums

Article abstract of DOI:10.1016/j.tet.2013.03.019

A variety of allylidenecyclopropanes and allylidenecyclobutanes were synthesized via the coupling reaction of cyclopropyl- and cyclobutylmagnesium carbenoids with α-sulfonylallyllithiums. Small ring cycloalkylmagnesium carbenoids were generated from aryl

Full text of DOI:10.1016/j.tet.2013.03.019

Tetrahedron 69 (2013) 3961e3970
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Synthesis of small ring-containing conjugated dienes via the
coupling reaction of cyclopropyl- and cyclobutylmagnesium
carbenoids with a-sulfonylallyllithiums
Tsutomu Kimura a, Mio Inumaru b, Takuma Migimatsu b, Masashi Ishigaki b,
,b,
Tsuyoshi Satoh a
*
a Department of Chemistry, Faculty of Science, Tokyo University of Science, 12 Ichigaya-funagawara-machi, Shinjuku-ku, Tokyo 162-0826, Japan
b Graduate School of Chemical Sciences and Technology, Tokyo University of Science, 12 Ichigaya-funagawara-machi, Shinjuku-ku, Tokyo 162-0826,
Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A variety of allylidenecyclopropanes and allylidenecyclobutanes were synthesized via the coupling re-
Received 9 February 2013
Received in revised form 27 February 2013
Accepted 5 March 2013
action of cyclopropyl- and cyclobutylmagnesium carbenoids with
cycloalkylmagnesium carbenoids were generated from aryl 1-chlorocycloalkyl sulfoxides and a Grignard
reagent, and the resultant magnesium carbenoids were reacted with -sulfonylallyllithiums, which were
prepared via the deprotonation of p-tolyl vinyl sulfones or allyl p-tolyl sulfones. Allylidenecycloalkanes
were obtained in moderate to good yields, and the DielseAlder reaction of allylidenecycloalkanes with
tetracyanoethylene afforded spirocyclic compounds. The coupling reaction of acyclic alkylmagnesium
a-sulfonylallyllithiums. Small ring
a
Available online 13 March 2013
Keywords:
Allylidenecycloalkane
Conjugated diene
Coupling reaction
[4þ2] Cycloaddition
Magnesium carbenoid
DFT calculation
carbenoids with a-sulfonylallyllithiums provided conjugated dienes as mixtures of geometric isomers.
The results from DFT calculations showed that small ring cycloalkylmagnesium carbenoids have a long
CeCl bond and expanded bond angles on the backside of the CeCl bond relative to those of the corre-
sponding chlorocycloalkanes.
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
We have developed an efficient method for the generation of
magnesium carbenoids 5e8 using a-chloro-substituted sulfoxides
Small ring hydrocarbons play an important role in organic
synthesis.1 Among these compounds, conjugated dienes bearing
a small ring at the terminal position, such as allylidenecyclopro-
panes and allylidenecyclobutanes, are versatile synthetic in-
termediates, especially as strain-activated dienes in the
DielseAlder reaction.2,3 Although several synthetic methods, such
as the Wittig or Peterson olefination-based approaches, have pre-
viously been reported,2e7 small ring-containing conjugated dienes
are still not readily accessible. The preparation of small ring
cycloalkylphosphonium halides from cycloalkyl halides and phos-
phines is difficult because of the poor reactivity of secondary small
ring cycloalkyl halides.8 In addition, the reaction of small ring
cycloalkylidene phosphoranes with carbonyl compounds often
proceeds with low efficiency.5,9 Multi-functionalized small ring
1e4 as key precursors (Scheme 1), and various types of synthetic
transformations have been achieved taking advantage of the di-
verse reactivity of magnesium carbenoids.10 In particular, small ring
cycloalkylmagnesium carbenoids 6 and 7 can be used as electro-
philes,11,12 whereas small ring cycloalkyl halides are less reactive
toward nucleophilic substitution.13 In addition, we found that
magnesium carbenoids 5e8 can be coupled with carbon nucleo-
philes, which have a leaving group on the carbanion center, through
a C]C double bond.11a,b,12b,14 For example, the reaction of magne-
sium alkylidene carbenoids 5 with a-sulfonylallyllithiums yielded
a variety of vinylallenes 9 in good yields (Scheme 1).14d Because
general methods for the synthesis of sulfoxides 2 and 3 have been
establised11,12 and both p-tolyl vinyl sulfones 13 and allyl p-tolyl
sulfones 14 can be used as
coupling reaction of small ring cycloalkylmagnesium carbenoids 6
and 7 with -sulfonylallyllithiums will provide a novel route for the
a
-sulfonylallyl anion sources,14d the
cycloalkanes are necessary for the generation of a-silylcycloalkyl
anions via the Peterson olefination.6
a
synthesis of small ring-containing conjugated dienes. Herein, we
report the synthesis of allylidenecyclobutanes 10 and allylidene-
cyclopropanes 11 via the coupling reaction of cyclobutyl-6 and
* Corresponding author. Tel.: þ81 (3)52288272; fax: þ81 (3)52614631; e-mail
address: tsatoh@rs.kagu.tus.ac.jp (T. Satoh).
cyclopropylmagnesium carbenoids 7 with a-sulfonylallyllithiums.
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.03.019

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T. Kimura et al. / Tetrahedron 69 (2013) 3961e3970
Table 1
Synthesis of allylidenecyclobutanes 10 from sulfoxides
sulfones 13
2
and p-tolyl vinyl
Entry 2
13
10
Yield (%)
69
1
2a 13a
10a
2
3
2a 13b
2a 13c
10b
10c
39
49
Scheme 1. Coupling reaction of magnesium carbenoids with a-sulfonylallyl anions.
The reaction of acyclic alkylmagnesium carbenoid 8 with a-sulfo-
nylallyllithiums leading to the formation of conjugated dienes 12 is
also described.
4
2a 13d
2a 13e
10d
64
2. Results and discussion
5a
10e
10e
10f
44
83
70
2.1. Synthesis of allylidenecyclobutanes
6a,b 2a 13e
First, we investigated the generation of a-sulfonylallyllithiums
from p-tolyl vinyl sulfones 13 (Scheme 2). When isocrotyl p-tolyl
sulfone 13a was treated with BuLi at ꢀ78 ꢁC for 5 min followed by
7
8
2a 13f
2a 13g
quenching with MeOD, a mixture of a-deuterated p-tolyl vinyl sul-
fone 13a-d and
a-deuterated allyl p-tolyl sulfone 14a-d was ob-
tained. On the other hand, when the reaction mixture was warmed
10g
78
to ꢀ70 ꢁC over a period of 10 min after treatment of sulfone 13a with
BuLi, a-deuterated allyl p-tolyl sulfone 14a-d was formed as the sole
product. These results indicated that the a-hydrogen atom of sulfone
13a was initially abstracted by BuLi, and the resultant vinyllithium
isomerized to allyllithium at an elevated temperature.15 We used
this deprotonationeisomerization procedure for the generation of
9
2a 13h
2a 13i
10h
10i
20
32
a
-sulfonylallyllithiums from p-tolyl vinyl sulfones 13.
10c
11d 2a 13j
12d,e 2a 13j
10j
10j
21
43
13
14
2b 13g
2c 13g
10k
10l
70
49
Scheme 2. Generation of a-sulfonylallyllithium from p-tolyl vinyl sulfone 13a.
a
Sulfone 13e was treated with LDA at 0 ꢁC for 1.5 h.
5 equiv of sulfone 13e and LDA were used.
Sulfone 13i was treated with LDA at 0 ꢁC for 30 min.
Sulfone 13j was treated with KHMDS at 0 ꢁC for 10 min.
5 equiv of sulfone 13j and KHMDS were used.
The synthesis of methallylidenecyclobutane 10a was performed
b
c
using 3,3-bis(ethoxymethyl)-substituted 1-chlorocyclobutyl p-tolyl
sulfoxide 2a and sulfone 13a (Table 1, entry 1).11b Cyclo-
butylmagnesium carbenoid was generated in situ from sulfoxide 2a
d
e
and EtMgCl at ꢀ90 ꢁC.16
a-Sulfonylallyllithium (3 equiv) was

T. Kimura et al. / Tetrahedron 69 (2013) 3961e3970
3963
concurrently generated by deprotonating sulfone 13a with BuLi
at ꢀ78 ꢁC followed by warming of the reaction mixture to ꢀ70 ꢁC.
tolyl sulfone 14f was more efficient than that with p-tolyl vinyl
sulfone 13e (Table 1, entry 5 and Table 2, entry 7). However,
a
-
The resulting solution containing
a-sulfonylallyllithium was added
methyl-substituted sulfone 14g was not suitable for the coupling
reaction because sulfone 14g could not be deprotonated using
strong bases, such as t-BuLi and alkali metal amides (entry 8).
Allylidenecyclobutanes 10a, 10d, and 10e could be converted to
spirocyclic compounds 15 using the DielseAlder reaction with
tetracyanoethylene (Table 3). The reaction occurred smoothly in
diethyl ether at room temperature within 15 min to afford [4þ2]
cycloadducts 15aec in 84e89% yield.
to the solution containing magnesium carbenoid through a cannula
at ꢀ90 ꢁC, and the reaction mixture was allowed to warm to 0 ꢁC.
The desired coupling product 10a was obtained in 69% yield.
We further investigated the scope and generality of this reaction
with various sulfones 13 and sulfoxides 2 (Table 1, entries 2e14).
The reaction with sulfone 13b bearing methyl and phenyl groups at
the b-position yielded (2-phenylallylidene)cyclobutane 10b in 39%
yield (entry 2). Allylidenecyclobutanes 10cee, which have an in-
ternal alkene unit, were obtained from sulfoxide 2a and acyclic and
cyclic sulfones 13cee in 44e64% yield (entries 3e5). When
Table 3
[4þ2] cycloaddition of allylidenecyclobutanes 10 with tetracyanoethylene
a
-substituted sulfones 13fej were used as a-sulfonylallyl anion
sources, coupling products 10fej with a tetrasubstituted alkene unit
were formed in variable yields (entries 7e11). The delocalization of
the negative charge over the phenyl or carbonyl group at the
a
-position resulted in the low nucleophilicity of
anions in the reaction with sulfones 13h and 13i (entries 9 and 10).
The generation of -sulfonylallyllithiums from sulfones 13e and 13j
a-sulfonylallyl
a
was performed at 0 ꢁC because the isomerization or deprotonation
did not proceed at low temperatures (entries 5 and 11). The anionic
species generated from sulfones 13e and 13j appeared to be un-
stable at 0 ꢁC, and their degradation resulted in low efficiency. The
use of 5 equiv of sulfones 13e and 13j improved the yield of products
10e and 10j (entries 6 and 12). 3,3-Bis(3-phenylpropoxymethyl)-
substituted sulfoxide 2b and unsubstituted sulfoxide 2c could also
be used as coupling partners (entries 13 and 14).
Entry
10
15
Yield (%)
R1
R2
H
1
10a
Me
15a
89
Next, we investigated the coupling reaction using sulfoxide 2a
and a range of allyl p-tolyl sulfones 14, which do not require an
2
3
10d
10e
e(CH2)3e
e(CH2)4e
15b
15c
86
84
isomerization process (Table 2).
a-Sulfonylallyllithiums generated
from unsubstituted and -disubstituted sulfones 14bed could be
g,g
coupled with cyclobutylmagnesium carbenoid to afford the corre-
sponding allylidenecyclobutanes 10meo in 67e87% yield (entries
1e3). The reaction with sulfones (E)-14e and (Z)-14e bearing a (E)-
and (Z)-cinnamyl group, respectively, proceeded without geometric
isomerization of the cinnamyl group to yield coupling products (E)-
10p and (Z)-10p, respectively (entries 4 and 5). Allylidenecyclobu-
tanes 10a and 10e, which were prepared from p-tolyl vinyl sulfones
13a and 13e, respectively, were also obtained from allyl p-tolyl
sulfones 14a and 14f (entries 6 and 7), and the reaction with allyl p-
2.2. Synthesis of allylidenecyclopropanes
Encouraged by the successful synthesis of allylidenecyclobutanes
Table 2
10, we attempted the coupling reaction of cyclopropylmagnesium
Synthesis of allylidenecyclobutanes 10 from sulfoxide 2a and allyl p-tolyl sulfones 14
carbenoids 7 with a-sulfonylallyllithiums (Table 4). Aryl 1-chlor-
ocyclopropyl sulfoxides 3 were treated with i-PrMgCl at ꢀ78 ꢁC,16
and a solution containing
a-sulfonylallyllithiums (2 equiv) was
added to the solution containing the cyclopropylmagnesium car-
benoids. Allylidenecyclopropanes 11aed were obtained in 42e95%
yield (entries 1e4), and the geometric ratio of the products was
dependent on the substituents on the cyclopropane ring (entries
1e3). Allylidenecyclopropanes 11 were more or less unstable at
room temperature, especially in the neat state, and gradually de-
graded. For example, allylidenecyclopropanes 11e and 11f appeared
to be included in the crude products. However, these compounds
decomposed during silica gel purification (entries 5 and 6). To
confirm the formation of allylidenecyclopropane 11f, the crude
product was immediately trapped by tetracyanoethylene
(Scheme 3). The [4þ2] cycloaddition proceeded with the degrada-
tion of diene 11f to yield spiro[2.5]oct-4-ene 16 as a mixture of di-
astereomers in low yield.
Entry
1
14
R1
H
R2
H
R3
H
R4
H
10
Yield (%)
87
14b
10m
2
14c
10n
84
3
4
5
6
14d
H
H
H
H
H
H
H
Me
Ph
H
Ph
H
Ph
Ph
H
10o
67
85
78
71
(E)-14e
(Z)-14e
14a
(E)-10p
(Z)-10p
10a
H
2.3. Synthesis of acyclic conjugated dienes
7
8
14f
10e
10q
82
0
The coupling reaction was also applied to the synthesis of acyclic
conjugated dienes (Table 5). Alkylmagnesium carbenoid was
14g
Me
Me
Me
Me

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T. Kimura et al. / Tetrahedron 69 (2013) 3961e3970
Table 4
Synthesis of allylidenecyclopropanes 11 from sulfoxides 3 and sulfones 13 and 14
Entry
3
R1
R2
Ar 13 11 R3
R4 R5 R6 Yield Geometric
(%)
ratio
1
2
3a CH2OTr
3b CH2OTBS
3c CH2Bn
H
H
Me
H
Tol 13a 11a
Tol 13a 11b
Tol 13a 11c
H
H
H
Me H
Me H
Me H
H
H
H
H
79
56
95
42
10:1
4:1
da
d
3
4b
3d
H
Ph 13g 11d CH2 Me H
PMB
5
6
3d
3e Me
H
H
Ph 14d 11e
H
H
H
Me H
Ph Ph
0
0
d
d
CH2OTr Tol 13a 11f
H
a
Diene 11c was obtained as a single isomer.
b
The reaction mixture was allowed to warm to ꢀ50 ꢁC and stirred at that tem-
perature for 3 h.
Scheme 4. Proposed mechanism for the coupling reaction of magnesium carbenoids
with -sulfonylallyl anions.
a
sulfoxides 2e4 with a Grignard reagent generates magnesium
carbenoids 6e8, and the deprotonation of vinyl p-tolyl sulfones 13
or allyl p-tolyl sulfones 14 with BuLi provides
The nucleophilic substitution of -sulfonylallyl anions with mag-
nesium carbenoids 6e8 primarily occurs at the -position on the
sulfonylallyl anions to afford intermediates 17.18 The
-elimination
a-sulfonylallyl anions.
a
a
a-
b
of magnesium 4-methylbenzenesulfinate chloride from in-
termediates 17 affords conjugated dienes 10e12.
As mentioned above, small ring cycloalkyl halides undergo nu-
cleophilic substitution reactions with very low efficiency.13 Indeed,
the reaction of chlorocyclobutane 18 with
did not occur at ꢀ90 ꢁC (Scheme 5, Eq. 1).
a-sulfonylallyllithium
Scheme 3. Synthesis of allylidenecyclopropane 11f and [4þ2] cycloaddition of 11f with
tetracyanoethylene.
generated from 3-(4-methoxyphenyl)propyl p-tolyl sulfoxide 4 and
i-PrMgCl,16,17 and the resulting alkylmagnesium carbenoid was
reacted with a-sulfonylallyllithiums generated from sulfones 13a,
13d, and 13f in a similar manner to the synthesis of allylidenecy-
cloalkanes. Conjugated dienes 12aec were formed in 60e85% yield
with low geometric selectivity.
2.4. Reaction mechanism
The mechanism of the coupling reaction is described below
(Scheme 4). The sulfoxideemagnesium exchange reaction of
Scheme 5. Reaction of chlorocyclobutanes with a-sulfonylallyllithium.
Table 5
Synthesis of conjugated dienes 12 from sulfoxide 4 and p-tolyl vinyl sulfones 13
The difficulty with the nucleophilic substitution at the carbon
atom of small ring cycloalkyl halides is primarily due to the in-
accessibilityof the backside of carbonehalogen bond to nucleophiles
and the increased internal ring strain in the transition state.13
However, the reaction of cyclobutylmagnesium carbenoid with
-sulfonylallyllithium occurred at ꢀ90 ꢁC to yield allylidenecyclo-
Entry
1
13
12
Yield (%)
85
E/Z ratio
a
butane 10a (Scheme 5, Eq. 2). To elucidate the curious reactivity
of small ring cycloalkylmagnesium carbenoids, DFT calculations
of chlorocyclobutane 180 and bis(dimethyl ether)-solvated
1-chlorocyclobutylmagnesium chloride 60$2(OMe2) were per-
formed using the 6-311þþG(d,p) basis set at the B3LYP level with the
Gaussian software program (Fig. 1).19e21 Selected structural param-
eters of model compounds 180 and 60$2(OMe2) are listed in Table 6
along with those of cyclopropane analogues 200 and 70$2(OMe2) in
the previous report.22 Small ring cycloalkylmagnesium carbenoids
13a
12a
12b
1:3
2
3
13d
13f
60
78
1:3
12c
1:2.4

T. Kimura et al. / Tetrahedron 69 (2013) 3961e3970
3965
terminal position via the coupling reaction of cyclopropyl- and
cyclobutylmagnesium carbenoids with -sulfonylallyllithiums. The
a
present synthetic method utilizes the electrophilicity of small ring
cycloalkylmagnesium carbenoids and is complementary to the
conventional synthetic methods using the chemistry of cycloalkyl
anions. Allylidenecyclopropane and allylidenecyclobutanes un-
derwent [4þ2] cycloaddition with tetracyanoethylene to afford
spiro[2.5]oct-4-ene and spiro[3.5]non-5-enes, respectively. The
results from DFT calculations of small ring cycloalkylmagnesium
carbenoids revealed that the presence of the magnesium atom on
the carbon atom bearing the chloro group results in enhanced
p-character of the carbon atom in the CeCl bond and facilitates the
nucleophilic substitution on the small carbon ring framework.
Further synthetic applications of small ring cycloalkylmagnesium
carbenoids as electrophiles are ongoing and will be reported in due
course.
4. Experimental
4.1. General method
The melting points were measured using a Yanaco MP-S3 ap-
paratus and are uncorrected. The NMR spectra were measured in
a CDCl3 solution with JEOL JNM-LA 300, JEOL JNM-LA 500, Bruker
AVANCE DPX 300, Bruker AVANCE DPX 400, and Bruker AVANCE
600 spectrometers. The stereochemistry of allylidenecyclobutane
10c, sulfone 13b, and [4þ2] cycloadducts 16 was assigned based on
their NOESY spectra. The assignments of the 13C NMR spectra were
made by DEPT 45, 90, and 135. The mass spectra (MS) were ob-
tained at 70 eV by direct injection with a HITACHI M-80B mass
spectrometer. The IR spectra were recorded on a PerkineElmer
Spectrum One FTIR instrument. Silica gel 60 N (Kanto Chemical)
containing 0.5% fluorescence reagent 254 and a quartz column
were used in the column chromatography, and the products that
absorbed UV light were detected by UV irradiation. Anhydrous THF
was purchased from Kanto Chemical and used as supplied. All of
the reactions involving air- or water-sensitive compounds were
routinely conducted in glassware that had been flame-dried under
a positive pressure of argon. Sulfoxides 2e4,11,12,17 p-tolyl vinyl
sulfones 13,14d and allyl p-tolyl sulfones 1414d were prepared
according to previously published protocols.
Fig. 1. CeCl anti-bonding orbital of model compounds: (a) chlorocyclobutane 180; and
(b) 1-chlorocyclobutylmagnesium chloride 60$2(OMe2). (c) HOMO of the
a-(phenyl-
sulfonyl)allyl anion.
Table 6
Selected parameters of model compounds
a
ꢀ
Compound
HCeCl
C2eCl (A)
BeC2eCl (ꢁ)b
BeC2eE (ꢁ)c
A (ꢁ)d
180
sp4.6
sp5.7
sp3.7
sp4.1
1.83
1.94
1.79
1.88
123.1
112.3
124.8
114.4
131.9
139.5
124.9
131.6
326.2
334.0
300.1
309.9
60$2(OMe2)
200
70$2(OMe2)
a
Hybridization of carbon atom in the CeCl bond.
An angle between the bisector of the C1eC2eC3 angle and the C2eCl bond.
An angle between the bisector of the C1eC2eC3 angle and the C2eE bond (E¼H
b
c
or Mg).
d
Sum of the C1eC2eE, EeC2eC3, and C3eC2eC1 angles (E¼H or Mg).
4.1.1. 1,1-Bis(ethoxymethyl)-3-(2-methylallylidene)cyclobutane
(10a). A 2.0 M solution of EtMgCl in THF (0.125 mL, 0.25 mmol) was
added dropwise to a solution of 2a (34.5 mg, 0.100 mmol) in THF
(1.0 mL) at ꢀ90 ꢁC, and the mixture was stirred at that temperature
for 1 min. In another flask, a 1.62 M solution of BuLi in hexane
(0.185 mL, 0.299 mmol) was added dropwise to a solution of 13a
(63.1 mg, 0.300 mmol) in THF (1.0 mL) at ꢀ78 ꢁC, and the mixture
was allowed to warm to ꢀ70 ꢁC over a period of 10 min. The re-
60$2(OMe2) and 70$2(OMe2) have a weakened CeCl bond and ex-
panded bond angles on the backside of CeCl bond compared to those
of the corresponding chlorocycloalkanes 180 and 200. The difference
in geometry between cycloalkylmagnesium carbenoids and chlor-
ocycloalkanes are attributed to the enhanced p-character of the
carbenoid carbon atom in the CeCl bond relative to that of chlor-
ocycloalkanes. These structural changes provide a favorable envi-
ronment for the nucleophilic substitution because the reaction
center is more accessible and the structures of the reactants ap-
proach to the transition state structures.
sultant solution of a-sulfonylallyllithium in THF was transferred to
a solution of magnesium carbenoid in THF through a cannula at
ꢀ90 ꢁC, and the reaction mixture was allowed to warm to 0 ꢁC over
a period of 80 min. The reaction was quenched with satd aq NH4Cl
(1.5 mL), and the mixture was extracted with CHCl3 (3ꢂ5 mL). The
combined organic layer was dried over MgSO4 and concentrated
under reduced pressure. The residue was purified by column
chromatography on silica gel (hexaneeEtOAc, 20:1) to yield 10a
(15.5 mg, 0.0691 mmol, 69%) as a colorless oil. When the reaction
was conducted on a 1 mmol scale, diene 10a was obtained in 59%
yield (133 mg, 0.592 mmol). IR (neat) 2975, 2931, 2866, 1669, 1608,
Another important point in the reaction mechanism is the
regioselectivity of the nucleophilic substitution of
lallyllithiums.23 In all of the cases, the reaction occurred at the
-position of the -sulfonylallyllithiums. The HOMO of the
(phenylsulfonyl)allyl anion is localized on the carbon atoms at the
- and -positions, and the coefficient of the HOMO at the -po-
a-sulfony-
a
a
a-
a
g
a
sition was larger than that at the g-position (Fig. 1c).
1456, 1409, 1376, 1354, 1176, 1112, 1070, 875 cmꢀ1
(500 MHz, CDCl3)
1.19 (t, J¼7.0 Hz, 6H), 1.85 (br s, 3H), 2.52 (br s,
2H), 2.75 (br s, 2H), 3.44 (s, 4H), 3.51 (q, J¼7.0 Hz, 4H), 4.74 (br s,
2H), 5.81e5.85 (m, 1H); 13C NMR (126 MHz, CDCl3)
15.1 (CH3ꢂ2),
21.0 (CH3), 37.4 (CH2), 37.6 (CH2), 39.4 (C), 66.7 (CH2ꢂ2), 73.5
;
1H NMR
3. Conclusion
d
We developed a useful method for the synthesis of multi-
substituted conjugated dienes bearing small ring at the
d
a

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T. Kimura et al. / Tetrahedron 69 (2013) 3961e3970
(CH2ꢂ2), 113.2 (CH2), 126.0 (CH), 138.3 (C), 142.6 (C); MS (EI) m/z (%)
224 (Mþ, 6), 119 (100), 117 (30), 105 (18), 93 (18), 91 (33), 79 (23), 59
(17); HRMS (EI) calcd for C14H24O2: 224.1776, found: 224.1774.
155 (13), 121 (100); HRMS (EI) calcd for C23H34O3: 358.2508, found:
358.2507.
4.1.8. {1-[3,3-Bis(ethoxymethyl)cyclobutylidene]-2-methylallyl}ben-
4.1.2. 1,1-Bis(ethoxymethyl)-3-(2-phenylallylidene)cyclobutane
zene (10h). Colorless oil; IR (neat) 2974, 2931, 2866, 1601, 1444,
(10b). Colorless oil; IR (neat) 2975, 2931, 2866, 1670, 1596, 1445,
1375, 1111, 1070, 700 cmꢀ1 1H NMR (300 MHz, CDCl3)
; d 1.18 (t,
1376, 1355, 1175, 1111, 1071, 1027, 888, 702 cmꢀ1
;
1H NMR
J¼7.0 Hz, 6H), 1.87 (br s, 3H), 2.49 (br s, 2H), 2.77 (br s, 2H), 3.44 (s,
4H), 3.52 (q, J¼7.0 Hz, 4H), 4.65 (br d, J¼1.7 Hz, 1H), 4.97 (br quint,
J¼1.7 Hz, 1H), 7.14e7.23 (m, 3H), 7.23e7.36 (m, 2H); MS (EI) m/z (%)
300 (Mþ, 13), 195 (100); HRMS (EI) calcd for C20H28O2: 300.2089,
found: 300.2088.
(300 MHz, CDCl3)
d
1.17 (t, J¼7.0 Hz, 6H), 2.26 (br s, 2H), 2.57 (br s,
2H), 3.39 (s, 4H), 3.48 (q, J¼7.0 Hz, 4H), 5.08 (br s,1H), 5.18 (br s,1H),
6.02 (br quint, J¼2.3 Hz, 1H), 7.21e7.36 (m, 5H); MS (EI) m/z (%) 286
(Mþ, 7), 194 (28), 181 (100), 178 (20), 167 (18), 155 (19), 141 (20), 91
(18); HRMS (EI) calcd for C19H26O2: 286.1933, found: 286.1934.
4.1.9. tert-Butyl 2-[3,3-bis(ethoxymethyl)cyclobutylidene]-3-methyl-
but-3-enoate (10i). Colorless oil; IR (neat) 2976, 2931, 2867, 1706
(C]O), 1662, 1638, 1368, 1321, 1253, 1177, 1156, 1113, 1030 cmꢀ1; 1H
4.1.3. (Z)-1,1-Bis(ethoxymethyl)-3-(2-ethylbut-2-en-1-ylidene)cyclo-
butane (10c). Colorless oil; IR (neat) 2974, 2932, 2867, 1664, 1464,
1445, 1375, 1354, 1175, 1112, 1070, 881 cmꢀ1
;
1H NMR (500 MHz,
NMR (300 MHz, CDCl3)
d
1.19 (t, J¼7.0 Hz, 6H), 1.48 (s, 9H), 1.86 (br s,
CDCl3)
d
0.98 (t, J¼7.5 Hz, 3H),1.19 (t, J¼7.0 Hz, 6H),1.65 (d, J¼6.9 Hz,
3H), 2.61 (br s, 2H), 2.83 (br s, 2H), 3.43 (s, 4H), 3.51 (q, J¼7.0 Hz, 4H),
4.74e4.78 (m, 1H), 4.98e5.03 (m, 1H); MS (FABþ) m/z (%) 325
([MþH]þ, 17), 269 (72), 268 (47), 251 (100), 177 (57), 147 (23), 131
(32), 59 (20); HRMS (FABþ) calcd for C19H32O4: 325.2379, found:
325.2377.
3H), 2.11 (q, J¼7.5 Hz, 2H), 2.55 (br s, 2H), 2.64 (br s, 2H), 3.45 (s,
4H), 3.51 (q, J¼7.0 Hz, 4H), 5.22 (q, J¼6.9 Hz,1H), 5.98e6.02 (m,1H);
MS (EI) m/z (%) 252 (Mþ, 115), 147 (100), 131 (17), 119 (22), 105 (23),
93 (18), 91 (19); HRMS (EI) calcd for C16H28O2: 252.2089, found:
252.2091.
4.1.10. 3-[3,3-Bis(ethoxymethyl)cyclobutylidene]cyclohex-1-ene
4.1.4. 1-{[3,3-Bis(ethoxymethyl)cyclobutylidene]methyl}cyclopent-1-
(10j). Colorless oil; IR (neat) 2975, 2931, 2864, 1682, 1611, 1376,
ene (10d). Colorless oil; IR (neat) 2974, 2931, 2865,1674,1376,1354,
1354,1175,1111,1069, 729 cmꢀ1; 1H NMR (300 MHz, CDCl3)
d 1.18 (t,
1175, 1111, 1070, 816 cmꢀ1
;
1H NMR (300 MHz, CDCl3)
d
1.18 (t,
J¼7.0 Hz, 6H), 1.66 (quint, J¼6.2 Hz, 2H), 2.06e2.18 (m, 4H), 2.44 (br
s, 2H), 2.48 (br s, 2H), 3.43 (s, 4H), 3.51 (q, J¼7.0 Hz, 4H), 5.68 (td,
J¼4.0, 9.9 Hz, 1H), 6.06 (td, J¼1.9, 9.9 Hz, 1H); MS (EI) m/z (%) 250
(Mþ, 9), 145 (100), 91 (17); HRMS (EI) calcd for C16H26O2: 250.1933,
found: 250.1935.
J¼7.0 Hz, 6H), 1.86 (quint, J¼7.5 Hz, 2H), 2.32 (br t, J¼7.5 Hz, 2H),
2.41e2.54 (m, 4H), 2.71 (br s, 2H), 3.44 (s, 4H), 3.50 (q, J¼7.0 Hz,
4H), 5.44e5.52 (m,1H), 5.92e6.00 (m,1H); MS (EI) m/z (%) 250 (Mþ,
15), 145 (100), 117 (17), 91 (22); HRMS (EI) calcd for C16H26O2:
250.1933, found: 250.1930.
4.1.11. 1-{3-[3,3-Bis(3-phenylpropoxymethyl)cyclobutylidene]-4-
methylpent-4-en-1-yl}-4-methoxybenzene (10k). Colorless oil; IR
(neat) 3027, 2933, 2857, 1611, 1512, 1497, 1454, 1246, 1177, 1112,
4.1.5. 1-{[3,3-Bis(ethoxymethyl)cyclobutylidene]methyl}cyclohex-1-
ene (10e). Colorless oil; IR (neat) 2975, 2931, 2858,1671,1445, 1376,
1354, 1111, 1070 cmꢀ1; 1H NMR (300 MHz, CDCl3)
d
1.18 (t, J¼7.0 Hz,
1039, 699 cmꢀ1 1H NMR (300 MHz, CDCl3)
; d 1.80e1.94 (m, 7H),
6H),1.49e1.66 (m, 4H), 2.07 (br s, 2H), 2.18 (br s, 2H), 2.49 (br s, 2H),
2.72 (br s, 2H), 3.43 (s, 4H), 3.50 (q, J¼7.0 Hz, 4H), 5.50e5.56 (m,
2.26e2.36 (m, 4H), 2.54e2.72 (m, 8H), 3.35 (s, 4H), 3.42 (t, J¼6.4 Hz,
4H), 3.75 (s, 3H), 4.90 (br s, 2H), 6.76e6.84 (m, 2H), 7.03e7.10 (m,
2H), 7.12e7.22 (m, 6H), 7.22e7.31 (m, 4H); MS (EI) m/z (%) 538 (Mþ,
1.6), 402 (8), 253 (36), 147 (21), 121 (100), 91 (78); HRMS (EI) calcd
for C37H46O3: 538.3447, found: 538.3452.
1H), 5.70 (br t, J¼2.3 Hz, 1H); 13C NMR (126 MHz, CDCl3)
d 15.1
(CH3ꢂ2), 22.2 (CH2), 22.8 (CH2), 25.7 (CH2), 26.7 (CH2), 37.4 (CH2),
37.8 (CH2), 39.4 (C), 66.6 (CH2ꢂ2), 73.5 (CH2ꢂ2), 125.8 (CH), 126.7
(CH),134.3 (C),136.3 (C); MS (EI) m/z (%) 264 (Mþ,17),159 (100),131
(17),117 (14), 91 (23), 79 (18), 59 (15); HRMS (EI) calcd for C17H28O2:
264.2089, found: 264.2086.
4.1.12. 1-(3-Cyclobutylidene-4-methylpent-4-en-1-yl)-4-methox-
ybenzene (10l). Colorless oil; IR (neat) 2947, 2859, 2834, 1648, 1612,
1512, 1464, 1455, 1443, 1300, 1246, 1176, 1040, 880, 820 cmꢀ1 1H
;
4.1.6. 1,1-Bis(ethoxymethyl)-3-(3-methylbut-3-en-2-ylidene)cyclo-
NMR (300 MHz, CDCl3) d 1.79e1.95 (m, 5H), 2.22e2.33 (m, 2H),
butane (10f). Colorless oil; IR (neat) 2975, 2931, 2865, 1661, 1606,
2.51e2.62 (m, 4H), 2.85 (br t, J¼7.2 Hz, 2H), 3.79 (s, 3H), 4.86 (br s,
1H), 4.88 (br s, 1H), 6.82 (d, J¼8.7 Hz, 2H), 7.08 (d, J¼8.7 Hz, 2H); MS
(EI) m/z (%) 242 (Mþ, 13), 121 (100); HRMS (EI) calcd for C17H22O:
242.1671, found: 242.1673.
1445, 1375, 1173, 1112, 1071, 877 cmꢀ1 1H NMR (300 MHz, CDCl3)
;
d
1.19 (t, J¼7.0 Hz, 6H), 1.62e1.66 (m, 3H), 1.90 (br s, 3H), 2.51 (br s,
2H), 2.71 (br s, 2H), 3.43 (s, 4H), 3.51 (q, J¼7.0 Hz, 4H), 4.77 (br s,
1H), 4.82 (br s, 1H); 13C NMR (126 MHz, CDCl3)
d
15.1 (CH3ꢂ2), 15.5
(CH3), 22.8 (CH3), 36.7 (CH2), 38.0 (C), 38.3 (CH2), 66.6 (CH2ꢂ2),
73.6 (CH2ꢂ2), 110.8 (CH2), 129.1 (C), 133.7 (C), 144.4 (C); MS (EI) m/z
(%) 238 (Mþ,13),133 (100),131 (18),105 (17), 93 (14), 91 (15); HRMS
(EI) calcd for C15H26O2: 238.1933, found: 238.1935.
4.1.13. 3-Allylidene-1,1-bis(ethoxymethyl)cyclobutane (10m). Colo
rless oil; IR (neat) 2976, 2932, 2866, 1677, 1608, 1412, 1377, 1354,
1175, 1112, 1071, 992, 894 cmꢀ1; 1H NMR (300 MHz, CDCl3)
d 1.18 (t,
J¼7.0 Hz, 6H), 2.51 (br s, 2H), 2.56 (br s, 2H), 3.43 (s, 4H), 3.50 (q,
J¼7.0 Hz, 4H), 4.92 (br dd, J¼0.9, 10.5 Hz, 1H), 5.02 (br dd, J¼0.9,
16.9 Hz, 1H), 5.87 (d of quintets, J¼2.2, 10.5 Hz, 1H), 6.26 (td, J¼10.5,
16.9 Hz, 1H); MS (EI) m/z (%) 210 (Mþ, 11), 117 (34), 105 (100), 91
(49), 79 (46), 59 (38); HRMS (EI) calcd for C13H22O2: 210.1620,
found: 210.1617.
4.1.7. 1-{3-[3,3-Bis(ethoxymethyl)cyclobutylidene]-4-methylpent-4-
en-1-yl}-4-methoxybenzene (10g). Colorless oil; IR (neat) 2973,
2932, 2901, 2863, 1652, 1612, 1512, 1464, 1444, 1375, 1300, 1246,
1176, 1110, 1039, 880, 819 cmꢀ1; 1H NMR (300 MHz, CDCl3)
d 1.17 (t,
J¼7.0 Hz, 6H), 1.88 (br s, 3H), 2.22e2.34 (m, 4H), 2.52e2.65 (m, 4H),
3.34 (s, 4H), 3.48 (q, J¼7.0 Hz, 4H), 3.78 (s, 3H), 4.89 (br s, 2H),
6.76e6.85 (m, 2H), 7.01e7.10 (m, 2H); 13C NMR (126 MHz, CDCl3)
4.1.14. {2-[3,3-Bis(ethoxymethyl)cyclobutylidene]ethylidene}cyclo-
hexane (10n). Colorless oil; IR (neat) 2974, 2929, 2854, 1633, 1446,
d
15.1 (CH3ꢂ2), 22.9 (CH3), 32.0 (CH2), 33.8 (CH2), 36.2 (CH2), 37.900
1376, 1354, 1175, 1111, 1070, 879 cmꢀ1 1H NMR (400 MHz, CDCl3)
;
(CH2), 37.904 (C), 55.2 (CH3), 66.609 (CH2), 66.611 (CH2), 73.5
(CH2ꢂ2), 111.6 (CH2), 113.5 (CH), 129.4 (CH), 133.2 (C), 134.1 (C),
134.7 (C), 142.7 (C), 157.7 (C); MS (EI) m/z (%) 358 (Mþ, 3), 253 (17),
d
1.18 (t, J¼7.0 Hz, 6H), 1.47e1.58 (m, 6H), 2.13 (br s, 2H), 2.20e2.27
(m, 2H), 2.50 (br s, 2H), 2.53 (br s, 2H), 3.43 (s, 4H), 3.50 (q, J¼7.0 Hz,
4H), 5.64 (d, J¼11.3 Hz, 1H), 6.07 (d of quintets, J¼2.3, 11.3 Hz, 1H);

T. Kimura et al. / Tetrahedron 69 (2013) 3961e3970
3967
13C NMR (126 MHz, CDCl3)
d
15.1 (CH3ꢂ2), 26.8 (CH2), 27.7 (CH2),
7.16e7.33 (m, 9HM, 9Hm), 7.40e7.52 (m, 6HM, 6Hm); MS (EI) m/z (%)
366 (Mþ, 0.3), 243 (100),165 (48),105 (29), 83 (32); HRMS (EI) calcd
for C27H26O: 366.1984, found: 366.1984.
28.6 (CH2), 29.0 (CH2), 35.0 (CH2), 36.5 (CH2), 37.3 (CH2), 39.1 (C),
66.6 (CH2ꢂ2), 73.5 (CH2ꢂ2), 117.7 (CH), 118.9 (CH), 137.1 (C), 139.9
(C); MS (EI) m/z (%) 278 (Mþ, 18), 232 (16), 173 (100), 131 (13), 105
(12), 91 (17); HRMS (EI) calcd for C18H30O2: 278.2246, found:
278.2245.
4.1.19. tert-Butyldimethyl{[2-(2-methylallylidene)cyclopropyl]me-
thoxy}silane (11b). A 4:1 mixture of geometric isomers; colorless
oil; IR (neat) 2956, 2930, 2896, 2858, 1618, 1472, 1464, 1257, 1144,
4.1.15. 1,1-Bis(ethoxymethyl)-3-(3,3-diphenylallylidene)cyclobutane
1089, 1006, 881, 836, 815, 776 cmꢀ1 1H NMR (300 MHz, CDCl3,
;
(10o). Colorless oil; IR (neat) 2974, 2931, 2866, 1661, 1597, 1494,
major: M, minor: m) d 0.06 (s, 6HM, 6Hm), 0.84e0.96 (m, 10HM,
1445, 1376, 1355, 1175, 1111, 1072, 1029, 764, 701 cmꢀ1
;
1H NMR
10Hm), 1.21e1.30 (m, 2HM, 2Hm), 1.92 (br s, 3HM), 1.96 (br s, 3Hm),
3.30 (dd, J¼8.2,10.7 Hz,1HM), 3.43 (dd, J¼7.5,10.8 Hz,1Hm), 3.68 (br
dd, J¼6.0,10.8 Hz,1Hm), 3.93 (ddd, J¼0.6, 5.0, 10.7 Hz,1HM), 4.92 (br
s, 1HM, 1Hm), 4.95 (br s, 1HM, 1Hm), 6.49 (br q, J¼1.7 Hz, 1HM), 6.51
(br q, J¼1.9 Hz, 1Hm); MS (EI) m/z (%) 238 (Mþ, 0.4), 181 (159), 163
(29), 127 (32), 115 (121), 93 (48), 75 (100), 73 (97), 59 (21); HRMS
(EI) calcd for C14H26OSi: 238.1753, found: 238.1754.
(300 MHz, CDCl3)
d
1.19 (t, J¼7.0 Hz, 6H), 2.50 (br s, 2H), 2.67 (br s,
2H), 3.45 (s, 4H), 3.51 (q, J¼7.0 Hz, 4H), 5.95 (d of quintets, J¼2.3,
11.4 Hz, 1H), 6.59 (d, J¼11.4 Hz, 1H), 7.17e7.42 (m, 10H); 13C NMR
(126 MHz, CDCl3)
d
15.1 (CH3ꢂ2), 35.4 (CH2), 36.9 (CH2), 39.2 (C),
66.7 (CH2ꢂ2), 73.5 (CH2ꢂ2), 121.5 (CH), 124.1 (CH), 126.9 (CH), 127.0
(CH), 127.3 (CH), 128.1 (CH), 130.5 (CH), 138.9 (C), 140.0 (C), 142.7
(C), 142.9 (C) (1 signals overlapping); MS (EI) m/z (%) 362 (Mþ, 37),
316 (26), 257 (100), 217 (17), 191 (25), 179 (18), 105 (23), 91 (17);
HRMS (EI) calcd for C25H30O2: 362.2246, found: 362.2247.
4.1.20. {2-[1-Methyl-2-(2-methylallylidene)cyclopropyl]ethyl}ben-
zene (11c). Single isomer; colorless oil; IR (neat) 3084, 3064, 3028,
2963, 2924, 2861, 1617, 1604, 1497, 1455, 1435, 1374, 881, 752,
4.1.16. (E)-1,1-Bis(ethoxymethyl)-3-(3-phenylallylidene)cyclobutane
[(E)-10p]. Colorless oil; IR (neat) 3023, 2974, 2931, 2866, 1667,
697 cmꢀ1
;
1H NMR (300 MHz, CDCl3)
d
0.90 (d, J¼8.7 Hz, 1H), 1.02
(d, J¼8.7 Hz,1H),1.28 (s, 3H),1.46 (ddd, J¼5.2,12.3,13.4 Hz,1H),1.88
(br s, 3H), 1.98e2.14 (m, 1H), 2.57 (ddd, J¼5.1, 11.5, 13.4 Hz, 1H),
2.64e2.80 (m, 1H), 4.89 (br s, 1H), 4.93 (br s, 1H), 6.40 (br s, 1H),
7.10e7.35 (m, 5H); MS (EI) m/z (%) 212 (Mþ, 1.4), 121 (100), 108 (76),
93 (82), 91 (71); HRMS (EI) calcd for C16H20: 212.1565, found:
212.1569.
1595, 1488, 1448, 1376, 1355, 1175, 1111, 1071, 965, 745, 692 cmꢀ1
;
1H NMR (300 MHz, CDCl3)
d
1.19 (t, J¼7.0 Hz, 6H), 2.57 (br s, 2H),
2.65 (br s, 2H), 3.46 (s, 4H), 3.52 (q, J¼7.0 Hz, 4H), 6.02 (d of
quintets, J¼2.2, 10.8 Hz, 1H), 6.37 (d, J¼15.7 Hz, 1H), 6.69 (dd,
J¼10.8, 15.7 Hz, 1H), 7.14e7.21 (m, 1H), 7.24e7.33 (m, 2H), 7.33e7.40
(m, 2H); MS (EI) m/z (%) 286 (Mþ, 19), 240 (18), 181 (100), 166 (14),
141 (17), 115 (15), 91 (16); HRMS (EI) calcd for C19H26O2: 286.1933,
found: 286.1930.
4.1.21. 1-(3-Cyclopropylidene-4-methylpent-4-en-1-yl)-4-methox-
ybenzene (11d). Colorless oil; IR (neat) 2950, 1612, 1512, 1454, 1246,
1177, 1038 cmꢀ1 1H NMR (300 MHz, CDCl3)
; d 0.77e0.87 (m, 2H),
4.1.17. (Z)-1,1-Bis(ethoxymethyl)-3-(3-phenylallylidene)cyclobutane
1.23e1.33 (m, 2H), 2.03 (br s, 3H), 2.61e2.80 (m, 4H), 3.78 (s, 3H),
4.97 (br s, 1H), 5.10 (br s, 1H), 6.77e6.84 (m, 2H), 7.04e7.11 (m, 2H);
MS (EI) m/z (%) 228 (Mþ, 10), 121 (100); HRMS (EI) calcd for
C16H20O: 228.1514, found: 228.1512.
[(Z)-10p]. Colorless oil; IR (neat) 2975, 2931, 2866, 1664, 1598,
1492, 1447, 1409, 1376, 1355, 1175, 1111, 1071, 769, 696 cmꢀ1 1H
;
NMR (400 MHz, CDCl3)
d
1.19 (t, J¼7.0 Hz, 6H), 2.55 (br s, 2H), 2.62
(br s, 2H), 3.45 (s, 4H), 3.51 (q, J¼7.0 Hz, 4H), 6.13 (t, J¼11.6 Hz, 1H),
6.28 (d, J¼11.6 Hz, 1H), 6.40e6.46 (m, 1H), 7.16e7.24 (m, 1H),
7.31e7.34 (m, 4H); MS (EI) m/z (%) 286 (Mþ, 19), 240 (18), 181 (100),
141 (16), 115 (14), 91 (14); HRMS (EI) calcd for C19H26O2: 289.1933,
found: 286.1932.
4.1.22. 1-Methoxy-4-(5-methylhexa-3,5-dien-1-yl)benzene (12a). A
1.02 M solution of t-BuMgCl in THF (0.098 mL, 0.100 mmol) was
added to a solution of 4 (30.9 mg, 0.100 mmol) in THF (1.0 mL) at
ꢀ78 ꢁC to remove a trace amount of water in the reaction media,
and the mixture was stirred at that temperature for 10 min. A 2.0 M
solution of i-PrMgCl in THF (0.14 mL, 0.28 mmol) was then added to
the solution at ꢀ78 ꢁC, and the mixture was stirred at that tem-
perature for 1 min. In another flask, a 1.62 M solution of BuLi in
hexane (0.185 mL, 0.299 mmol) was added dropwise to a solution of
13a (63.1 mg, 0.300 mmol) in THF (1.0 mL) at ꢀ78 ꢁC, and the
mixture was allowed to warm to ꢀ70 ꢁC over a period of 10 min.
4.1.18. 2-(2-Methylallylidene)-1-(trityloxymethyl)cyclopropane
(11a). A 2.0 M solution of i-PrMgCl in THF (0.125 mL, 0.25 mmol)
was added dropwise to a solution of 3a (50.1 mg, 0.100 mmol) in
THF (1.0 mL) at ꢀ78 ꢁC, and the mixture was stirred at that tem-
perature for 1 min. In another flask, a 1.62 M solution of BuLi in
hexane (0.125 mL, 0.202 mmol) was added dropwise to a solution
of 13a (42.1 mg, 0.200 mmol) in THF (1.0 mL) at ꢀ78 ꢁC, and the
mixture was allowed to warm to ꢀ70 ꢁC over a period of 10 min.
The resulting solution of a-sulfonylallyllithium in THF was trans-
ferred to a solution of magnesium carbenoid in THF through
a cannula at ꢀ78 ꢁC. The reaction mixture was allowed to warm to
ꢀ40 ꢁC over a period of 50 min and stirred at ꢀ40 ꢁC for 1 h. The
reaction was quenched with satd aq NH4Cl (1.5 mL), and the mix-
ture was extracted with CHCl3 (3ꢂ5 mL). The combined organic
layer was dried over MgSO4 and concentrated under reduced
pressure. The residue was purified by column chromatography on
silica gel (hexaneeEtOAc, 20:1) to afford 12a (17.2 mg,
0.0851 mmol, 85%, a mixture of geometric isomers, E:Z¼1:3) as
a colorless oil. IR (neat) 3002, 2934, 1612, 1513, 1464, 1455, 1442,
The resulting solution of a-sulfonylallyllithium in THF was trans-
ferred to a solution of magnesium carbenoid in THF through
a cannula at ꢀ78 ꢁC, and the reaction mixture was allowed to warm
to 0 ꢁC over a period of 60 min. The reaction was quenched with
satd aq NH4Cl (1.5 mL), and the mixture was extracted with CHCl3
(3ꢂ5 mL). The combined organic layer was dried over MgSO4 and
concentrated under reduced pressure. The residue was purified by
column chromatography on silica gel (hexaneeCHCl3, 4:1) to afford
11a (28.9 mg, 0.0789 mmol, 79%, a 10:1 mixture of geometric iso-
mers) as a colorless oil. IR (neat) 3085, 3059, 3033, 2973, 2918, 1617,
1597, 1491, 1449, 1219, 1153, 1062, 1033, 909, 885, 762, 746, 734,
1300, 1247, 1178, 1039, 890, 825 cmꢀ1 1H NMR (300 MHz, CDCl3)
;
d
1.83 (br t, J¼1.0 Hz, 3HE), 1.85 (br t, J¼1.0 Hz, 3HZ), 2.33e2.71 (m,
706, 633 cmꢀ1
;
1H NMR (500 MHz, CDCl3, major: M, minor: m)
4HE, 4HZ), 3.786 (s, 3HZ), 3.790 (s, 3HE), 4.79e4.96 (m, 2HE, 2HZ),
5.43 (td, J¼7.0,11.8 Hz,1HZ), 5.69 (br td, J¼6.9,15.6 Hz,1HE), 5.85 (br
qd, J¼1.2, 11.8 Hz, 1HZ), 6.17 (br td, J¼1.2, 15.6 Hz, 1HE), 6.78e6.87
(m, 2HE, 2HZ), 7.06e7.15 (m, 2HE, 2HZ); 13C NMR (126 MHz, CDCl3)
d
0.91e0.98 (m, 1HM), 1.03e1.13 (m, 1Hm), 1.23e1.31 (m, 1HM, 1Hm),
1.80 (br s, 3HM), 1.82e1.90 (m, 1HM, 1Hm), 1.93 (br s, 3Hm), 2.89 (dd,
J¼7.7, 9.5 Hz, 1HM), 2.92 (dd, J¼7.4, 9.8 Hz, 1Hm), 3.33 (dd, J¼5.3,
9.8 Hz, 1Hm), 3.36 (dd, J¼5.0, 9.5 Hz, 1HM), 4.87 (br s, 1HM), 4.92 (br
s, 1HM, 1Hm), 4.94 (br s, 1Hm), 6.46 (br s, 1HM), 6.54 (br s, 1Hm),
d
18.7, 23.3, 30.7, 34.9, 35.0, 35.4, 55.3, 113.7, 114.5, 115.2, 129.3,
130.0, 130.7, 131.3, 133.2, 134.0, 141.8, 157.8 (6 signals overlapping);

3968
T. Kimura et al. / Tetrahedron 69 (2013) 3961e3970
MS (EI) m/z (%) 202 (Mþ, 17), 121 (100); HRMS (EI) calcd for
C14H18O: 202.1358, found: 202.1357.
16), 121 (100); HRMS (EI) calcd for C20H24O3S: 344.1446, found:
344.1447.
4.1.23. 1-[4-(Cyclopent-1-en-1-yl)but-3-en-1-yl]-4-methoxybenzene
(12b). A mixture of geometric isomers (E:Z¼1:3); colorless oil; IR
(neat) 2951, 2932, 2842, 1612, 1512, 1464, 1442, 1300, 1246, 1177,
4.1.29. 1-Methyl-4-[(2-methyl-1-phenylprop-1-en-1-yl)sulfonyl]ben-
zene (13h). Colorless crystals (hexaneeEtOAc); mp 100.0e100.5 ꢁC;
IR (KBr) 2926, 1618, 1594, 1492, 1443, 1308, 1301, 1287, 1252, 1143,
1087, 1073, 933, 903, 815, 765, 706, 687 cmꢀ1; 1H NMR (300 MHz,
CDCl3) d 1.62 (s, 3H), 2.39 (br s, 3H), 2.42 (s, 3H), 6.95e7.02 (m, 2H),
7.15e7.32 (m, 5H), 7.47e7.54 (m, 2H); Anal. Calcd for C17H18O2S: C
1038, 821 cmꢀ1; 1H NMR (300 MHz, CDCl3)
d
1.90 (quint, J¼7.4 Hz,
2HZ), 2.00e2.10 (m, 2HE), 2.29e2.44 (m, 3HE, 3HZ), 2.49e2.76 (m,
5HE, 5HZ), 3.79 (br s, 3HE, 3HZ), 5.38 (td, J¼7.0, 11.7 Hz, 1HZ),
5.52e5.69 (m, 2HE, 1HZ), 6.03 (br d, J¼11.7 Hz, 1HZ), 6.30 (br d,
J¼15.6 Hz, 1HE), 6.79e6.87 (m, 2HE, 2HZ), 7.07e7.15 (m, 2HE, 2HZ);
MS (EI) m/z (%) 228 (Mþ, 9), 121 (100); HRMS (EI) calcd for C16H20O:
228.1514, found: 228.1515.
71.30, H 6.34, S 11.20; found C 71.23, H 6.32, S 11.23.
4.1.30. 1-[(2-Cyclohexylideneethyl)sulfonyl]-4-methylbenzene
(14c). Colorless crystals (hexaneeEtOAc); mp 69.5e70.0 ꢁC; IR
(KBr) 2934, 2846, 1448, 1315, 1302, 1291, 1161, 1141, 1124, 1087,
4.1.24. 1-(4,5-Dimethylhexa-3,5-dien-1-yl)-4-methoxybenzene
(12c). A 1:2.4 mixture of geometric isomers; colorless oil; IR (neat)
3030, 2994, 2932, 2855, 2834, 1611, 1584, 1512, 1464, 1441, 1374,
755 cmꢀ1; 1H NMR (300 MHz, CDCl3)
d 1.13e1.25 (m, 2H), 1.39e1.51
(m, 4H), 1.81 (br dt, J¼0.9, 6.2 Hz, 2H), 2.03e2.12 (m, 2H), 2.44 (s,
3H), 3.79 (d, J¼8.0 Hz, 2H), 5.13 (br tt, J¼0.9, 8.0 Hz, 1H), 7.29e7.35
1300, 1246, 1177, 1039, 885, 821 cmꢀ1
;
1H NMR (300 MHz, CDCl3,
(m, 2H), 7.70e7.77 (m, 2H); 13C NMR (126 MHz, CDCl3)
d 21.5 (CH3),
major: M, minor: m)
d
1.74 (br t, J¼1.1 Hz, 3Hm), 1.76 (br s, 3HM,
26.3 (CH2), 26.9 (CH2), 28.0 (CH2), 28.7 (CH2), 37.1 (CH2), 55.3 (CH2),
107.2 (CH), 128.6 (CH), 129.5 (CH), 135.8 (C), 144.3 (C), 150.1 (C);
Anal. Calcd for C15H20O2S: C 68.14, H 7.62, S 12.13; found C 68.38, H
7.45, S 12.28.
3Hm), 1.89 (br d, J¼0.7 Hz, 3HM), 2.27e2.37 (m, 2Hm), 2.42 (br q,
J¼7.4 Hz, 2HM), 2.53e2.60 (m, 2Hm), 2.60e2.69 (m, 2HM), 3.78 (br s,
3Hm), 3.79 (br s, 3HM), 4.60e4.63 (m, 1Hm), 4.86e4.90 (m, 1HM,
1Hm), 4.96e4.99 (m, 1HM), 5.19 (qt, J¼1.5, 7.2 Hz, 1Hm), 5.63 (br t,
J¼7.4 Hz, 1HM), 6.78e6.87 (m, 2HM, 2Hm), 7.05e7.15 (m, 2HM, 2Hm);
MS (EI) m/z (%) 216 (Mþ, 12), 121 (100); HRMS (EI) calcd for
C15H20O: 216.1514, found: 216.1516.
4.1.31. (3-Tosylprop-1-ene-1,1-diyl)dibenzene (14d). Colorless crys-
tals (hexaneeEtOAc); mp 128.1e128.9 ꢁC; IR (KBr) 2967, 2923,1595,
1490, 1445, 1314, 1290, 1226, 1167, 1133, 1084, 888, 774, 749, 709,
700, 640 cmꢀ1 1H NMR (300 MHz, CDCl3)
; d 2.44 (s, 3H), 3.90 (d,
4.1.25. 1-Methyl-4-[(2-methylprop-1-en-1-yl)sulfonyl]benzene
(13a). Colorless crystals (hexaneeEtOAc); mp 64.5e65.0 ꢁC; IR
(KBr) 3041, 2978, 1634, 1597, 1496, 1443, 1375, 1320, 1285, 1180,
J¼7.9 Hz, 2H), 6.13 (t, J¼7.9 Hz, 1H), 6.67e6.73 (m, 2H), 7.14e7.32
(m, 10H), 7.66 (d, J¼8.2 Hz, 2H); 13C NMR (126 MHz, CDCl3)
d 21.6,
57.5, 114.2, 127.3, 127.7, 128.1, 128.21, 128.24, 128.4, 129.2,
129.6135.7, 137.8, 140.8, 144.5, 149.5; MS (EI) m/z (%) 348 (Mþ, 1),
193 (100),178 (15), 115 (36), 91 (14); HRMS (EI) calcd for C22H20O2S:
348.1184, found: 348.1181.
1141, 1087, 874, 812, 778 cmꢀ1; 1H NMR (300 MHz, CDCl3)
d 1.88 (d,
J¼1.3 Hz, 3H), 2.14 (d, J¼1.3 Hz, 3H), 2.43 (s, 3H), 6.17 (septet,
J¼1.3 Hz, 1H), 7.29e7.37 (m, 2H), 7.75e7.83 (m, 2H); 13C
NMR (126 MHz, CDCl3)
d 19.0 (CH3), 21.5 (CH3), 26.9 (CH3), 126.4
(CH), 127.0 (CH), 129.6 (CH), 139.4 (C), 143.8 (C), 153.6 (C); Anal.
Calcd for C11H14O2S: C 62.83, H 6.71, S 15.25; found C 62.58, H 6.59,
S 15.30.
4.1.32. 2,2-Bis(ethoxymethyl)-8-methylspiro[3.5]non-8-ene-5,5,6,6-
tetracarbonitrile (15a). Tetracyanoethylene (21.5 mg, 0.168 mmol)
was added to a solution of 10a (25.1 mg, 0.112 mmol) in Et2O
(2.0 mL) at room temperature, and the mixture was stirred at that
temperature for 15 min. The mixture was filtered through a bed of
CeliteÒ and concentrated under reduced pressure. The residue was
purified by column chromatography on silica gel (hexaneeEtOAc,
10:1) to give 15a (35.1 mg, 0.0997 mmol, 89%) as a yellow oil. IR
(neat) 2978, 2934, 2873, 2256 (CN), 1445, 1379, 1356, 1174, 1113,
4.1.26. (E)-1-Methyl-4-[(2-phenylprop-1-en-1-yl)sulfonyl]benzene
(13b). Colorless crystals (hexaneeEtOAc); mp 96.5e97.0 ꢁC; IR
(KBr) 3055, 1595, 1443, 1311, 1300, 1289, 1141, 1082, 828, 813, 791,
753 cmꢀ1 1H NMR (300 MHz, CDCl3)
; d 2.44 (s, 3H), 2.52 (d,
J¼1.2 Hz, 3H), 6.59 (q, J¼1.2 Hz, 1H), 7.31e7.42 (m, 7H), 7.81e7.88
(m, 2H); Anal. Calcd for C16H16O2S: C 70.56, H 5.92, S 11.77; found C
70.52, H 5.96, S 11.76.
1074, 913, 879, 735 cmꢀ1 1H NMR (300 MHz, CDCl3)
; d 1.19 (t,
J¼7.0 Hz, 3H), 1.26 (t, J¼7.0 Hz, 3H), 1.84 (br s, 3H), 2.38 (dd, J¼1.6,
12.9 Hz, 2H), 2.59 (dd, J¼1.6, 12.9 Hz, 2H), 2.93 (br s, 2H), 3.44 (s,
2H), 3.50 (s, 2H), 3.51 (q, J¼7.0 Hz, 2H), 3.57 (q, J¼7.0 Hz, 2H), 6.31
4.1.27. 1-[(Cyclohexylidenemethyl)sulfonyl]-4-methylbenzene
(13e). Colorless crystals (hexaneeEtOAc); mp 37.0e37.6 ꢁC; IR
(KBr) 2945, 2936, 2855, 1620, 1443, 1310, 1297, 1288, 1141, 1085,
(br sextet, J¼1.6 Hz, 1H); 13C NMR (126 MHz, CDCl3)
d 14.9 (CH3),
15.1 (CH3), 22.6 (CH3), 36.5 (CH2), 36.75 (C), 36.77 (C), 37.3 (CH2ꢂ2),
39.2 (C), 48.2 (C), 66.9 (CH2ꢂ2), 73.6 (CH2), 74.3 (CH2), 110.7 (Cꢂ2),
110.9 (Cꢂ2), 124.6 (C), 127.7 (CH); MS (EI) m/z (%) 352 (Mþ, 2), 306
(36), 251 (34), 222 (26), 98 (47), 85 (22), 72 (25), 59 (100); HRMS
(EI) calcd for C20H24N4O2: 352.1899, found: 352.1898.
813, 792 cmꢀ1; 1H NMR (300 MHz, CDCl3)
d 1.50e1.66 (m, 6H), 2.14
(br t, J¼5.7 Hz, 2H), 2.41 (s, 3H), 2.71 (br t, J¼5.7 Hz, 2H), 6.10e6.13
(m, 1H), 7.30 (d, J¼8.1 Hz, 2H), 7.76 (d, J¼8.1 Hz, 2H); 13C NMR
(126 MHz, CDCl3)
d 21.5, 25.7, 27.3, 28.3, 29.3, 37.5, 123.7, 127.0,
129.7, 139.9, 143.7, 160.9; Anal. Calcd for C14H18O2S: C 67.16, H 7.25,
S 12.81; found C 66.83, H 7.21, S 12.78.
4.1.33. 3,3-Bis(ethoxymethyl)-10,20,30,7a’-tetrahydrospiro[cyclobutane-
1,50-indene]-60,60,70,70-tetracarbonitrile (15b). Yellow oil; IR (neat)
2977, 2934, 2874, 2256 (CN), 1378, 1356, 1165, 1112, 1073, 912,
4.1.28. 1-Methoxy-4-(4-methyl-3-tosylpent-3-en-1-yl)benzene
(13g). Colorless crystals (hexaneeEtOAc); mp 90.5e91.1 ꢁC; IR
(KBr) 2937, 1633,1610,1512, 1457, 1444,1299,1245, 1172,1137,1085,
735 cmꢀ1; 1H NMR (300 MHz, CDCl3)
d
1.20 (t, J¼7.0 Hz, 3H), 1.25 (t,
J¼7.0 Hz, 3H), 1.65e1.89 (m, 2H), 1.91e2.08 (m, 1H), 2.27e2.62 (m,
6H), 2.74 (br d, J¼13.7 Hz, 1H), 3.10e3.21 (m, 1H), 3.38e3.61 (m, 8H),
6.32 (br q, J¼2.2 Hz, 1H); MS (EI) m/z (%) 378 (Mþ, 20), 332 (26), 248
(24), 221 (21), 98 (44), 85 (31), 59 (100); HRMS (EI) calcd for
C22H26N4O2: 378.2056, found: 378.2056.
1029, 814, 692, 601 cmꢀ1; 1H NMR (500 MHz, CDCl3)
d 1.78 (s, 3H),
2.13 (s, 3H), 2.42 (s, 3H), 2.64e2.70 (m, 2H), 2.72e2.78 (m, 2H), 3.79
(s, 3H), 6.82 (d, J¼8.5 Hz, 2H), 7.10 (d, J¼8.5 Hz, 2H), 7.31 (d,
J¼8.3 Hz, 2H), 7.77 (d, J¼8.3 Hz, 2H); 13C NMR (126 MHz, CDCl3)
d
21.5 (CH3), 22.2 (CH3), 23.8 (CH3), 32.7 (CH2), 34.8 (CH2), 55.2
(CH3), 113.8 (CH), 127.0 (CH), 129.4 (CH), 129.5 (CH), 133.2 (C), 135.7
4.1.34. 3,3-Bis(ethoxymethyl)-50,60,70,80-tetrahydro-3’H-spiro[cyclobut-
ane-1,20-naphthalene]-30,30,40,40(4a’H)-tetracarbonitrile (15c). Yellow
(C), 139.7 (C), 143.5 (C), 148.1 (C), 157.9 (C); MS (EI) m/z (%) 344 (Mþ,

T. Kimura et al. / Tetrahedron 69 (2013) 3961e3970
3969
oil; IR (neat) 2977, 2940, 2867, 2255 (CN), 1449, 1378,1163, 1112, 1073,
913, 735 cmꢀ1; 1H NMR (300 MHz, CDCl3)
Supplementary data
d
1.19 (t, J¼7.0 Hz, 3H), 1.26
(t, J¼7.0 Hz, 3H), 1.30e1.68 (m, 3H), 1.80e1.94 (m, 1H), 1.96e2.21
(m, 2H), 2.24e2.48 (m, 5H), 2.75 (br d, J¼14.1 Hz, 1H), 2.86e2.97 (m,
1H), 3.39e3.63 (m, 8H), 6.20 (br septet, J¼2.0 Hz, 1H); 13C NMR
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.03.019.
(126 MHz, CDCl3)
d 14.9 (CH3), 15.2 (CH3), 24.7 (CH2), 25.4 (CH2),
References and notes
29.7 (CH2), 34.0 (CH2), 36.8 (C), 37.5 (CH2ꢂ2), 39.1 (C), 42.4 (CH), 43.4
(C), 48.9 (C), 66.9 (CH2ꢂ2), 73.6 (CH2), 74.3 (CH2), 109.2 (C), 110.0
(C), 111.7 (C), 111.8 (C), 125.9 (CH), 131.2 (C); MS (EI) m/z (%) 392
(Mþ, 6), 364 (50), 346 (36), 291 (32), 262 (27), 235 (26), 98 (63), 85
(39), 59 (100); HRMS (EI) calcd for C23H28N4O2: 392.2212, found:
392.2205.
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4.1.35. (1R*,3R*)-1,7-Dimethyl-1-[(trityloxy)methyl]spiro[2.5]oct-7-
ene-4,4,5,5-tetracarbonitrile [(1R*,3R*)-16]. Colorless crystals; mp
216.5e217.0 ꢁC; IR (KBr) 3059, 2918, 2868, 2256 (CN), 1491, 1449,
1076, 994, 904, 779, 770, 749, 733, 706, 633 cmꢀ1 1H NMR
;
(300 MHz, CDCl3)
d
1.18 (d, J¼7.1 Hz, 1H), 1.62 (d, J¼7.1 Hz, 1H), 1.69
(br s, 3H),1.84 (s, 3H), 2.78 (d, J¼10.2 Hz,1H), 2.87 (d, J¼17.9 Hz,1H),
3.16 (br d, J¼17.9 Hz, 1H), 3.53 (d, J¼10.2 Hz, 1H), 4.75 (br s, 1H),
7.21e7.37 (m, 9H), 7.38e7.47 (m, 6H); 13C NMR (126 MHz, CDCl3)
4. Brandi, A.; Goti, A. Chem. Rev. 1998, 98, 589.
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Tetrahedron Lett. 1988, 29, 25.
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Wang, F.-C.; Yeh, M.-C. P.; Sheu, J.-H. J. Organomet. Chem. 1994, 474, 123; (c)
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d
18.2 (CH3), 22.7 (CH3), 25.5 (CH2), 28.1 (C), 29.4 (C), 36.1
(CH2), 40.6 (C), 44.0 (C), 67.2 (CH2), 86.4 (C),110.2 (C),110.4 (C),111.4
(C), 111.8 (C), 122.6 (CH), 126.7 (C), 127.3 (CH), 127.9 (CH),
128.622 (CH), 128.624 (CH), 143.2 (C) (7 signals overlapping); MS
(FABþ) m/z (%) 531 ([MþNa]þ, 9), 243 (100), 165 (31), 154 (25), 115
(67), 93 (23); HRMS (FABþ) calcd for C34H28N4ONa: 531.2161,
found: 531.2162.
4.1.36. (1R*,3S*)-1,7-Dimethyl-1-[(trityloxy)methyl]spiro[2.5]oct-7-
ene-4,4,5,5-tetracarbonitrile [(1R*,3S*)-16]. Colorless crystals; mp
65.0e65.5 ꢁC; IR (KBr) 3059, 3034, 2940, 2254 (CN), 1491, 1449,
1221, 1070, 1032, 1001, 902, 777, 768, 750, 707, 633 cmꢀ1; 1H NMR
8. (a) Schweizer, E. E.; Berninger, C. J.; Thompson, J. G. J. Org. Chem. 1968, 33, 336;
(b) Utimoto, K.; Tamura, M.; Sisido, K. Tetrahedron 1973, 29, 1169.
9. (a) Felix, R. J.; Weber, D.; Gutierrez, O.; Tantillo, D. J.; Gagne, M. R. Nat. Chem.
2012, 4, 405; (b) Scherer, K. V., Jr.; Lunt, R. S., III. J. Organomet. Chem. 1965, 30,
3215; (c) Bestmann, H. J.; Kranz, E. Chem. Ber. 1969, 102, 1802.
(300 MHz, CDCl3)
d
1.17 (d, J¼7.1 Hz, 1H), 1.45 (s, 3H), 1.68 (d,
10. (a) Satoh, T. Chem. Rec. 2004, 3, 329; (b) Satoh, T. Chem. Soc. Rev. 2007, 36, 1561;
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magnesium Compounds; Rappoport, Z., Marek, I., Eds.; John Wiley & Sons:
Chichester, UK, 2008; p 717.
11. (a) Satoh, T.; Kasuya, T.; Ishigaki, M.; Inumaru, M.; Miyagawa, T.; Nakaya, N.;
Sugiyama, S. Synthesis 2011, 397; (b) Ishigaki, M.; Inumaru, M.; Satoh, T. Tet-
rahedron Lett. 2011, 52, 5563; (c) Satoh, T.; Kimura, T.; Sasaki, Y.; Nagamoto, S.
Synthesis 2012, 44, 2091.
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Saito, S. Tetrahedron Lett. 2004, 45, 347; (c) Satoh, T.; Miura, M.; Sakai, K.;
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52, 4468.
J¼7.1 Hz, 1H), 1.89 (br s, 3H), 2.89 (d, J¼17.9 Hz, 1H), 3.11 (br d,
J¼17.9 Hz, 1H), 3.51 (d, J¼10.6 Hz, 1H), 3.66 (d, J¼10.6 Hz, 1H),
5.35e5.40 (m, 1H), 7.22e7.37 (m, 9H), 7.45e7.53 (m, 6H); 13C NMR
(126 MHz, CDCl3) d 19.9 (CH3), 23.1 (CH3), 26.8 (CH2), 28.7 (C), 29.9
(C), 36.1 (CH2), 41.1 (C), 44.9 (C), 65.7 (CH2), 87.3 (C), 110.0 (C), 110.4
(C), 110.8 (C), 111.3 (C), 122.0 (CH), 127.3 (CH), 127.8 (CH), 127.9 (CH),
128.1 (C), 128.7 (CH), 128.8 (CH), 143.3 (C) (6 signals overlapping);
MS (FABþ) m/z (%) 531 ([MþNa]þ, 14), 243 (100), 165 (39), 115 (16),
105 (14); HRMS (FABþ) calcd for C34H28N4ONa: 531.2161, found:
531.2158.
13. Brown, H. C.; Fletcher, R. S.; Johannesen, R. B. J. Am. Chem. Soc. 1951, 73, 212.
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51, 966; (b) Satoh, T.; Kondo, A.; Musashi, J. Tetrahedron 2004, 60, 5453; (c)
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4.2. DFT calculations
The DFT calculations were performed with Gaussian 03 soft-
ware. The geometries were fully optimized in the gas phase without
symmetry constraints at the B3LYP/6-311þþG(d,p) level. The fre-
quency calculations at the same level of theory were performed to
determine whether the structures corresponded to energy minima
(no imaginary frequencies). Natural bond orbital (NBO) analysis
was performed at the B3LYP/6-311þþG(d,p) level using NBO ver-
sion 3.1, which is a program contained in the Gaussian 03
package.22
16. Excess Grignard reagents were necessary for the complete consumption of
sulfoxides 2e4.
17. (a) Satoh, T.; Osawa, A.; Ohbayashi, T.; Kondo, A. Tetrahedron 2006, 62, 7892; (b)
Tanaka, S.; Anai, T.; Tadokoro, M.; Satoh, T. Tetrahedron 2008, 64, 7199; (c)
Mitsunaga, S.; Ohbayashi, T.; Sugiyama, S.; Saitou, T.; Tadokoro, M.; Satoh, T.
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Acknowledgements
We wish to acknowledge support from a Grant-in-Aid for Sci-
entific Research No. 22590021 from the Ministry of Education,
Culture, Sports, Science and Technology, Japan, and a TUS Grant for
Research Promotion from Tokyo University of Science. High per-
formance computing resources were provided by the Tokyo Uni-
versity of Science.

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