Synthesis of multi-substituted cyclobutanes and alkylidenecyclobutanes by the reaction of cyclobutylmagnesium carbenoids with nucleophiles

Article abstract of DOI:10.1055/s-0030-1258391

Treatment of 1-chlorocyclobutyl p-tolyl sulfoxides with Grignard reagents such as ethylmagnesium chloride, isopropylmagnesium chloride, and cyclopentylmagnesium chloride in THF at low temperature gave cyclobutylmagnesium carbenoids in high yields. The gen

Full text of DOI:10.1055/s-0030-1258391

PAPER
397
Synthesis of Multi-Substituted Cyclobutanes and Alkylidenecyclobutanes by
the Reaction of Cyclobutylmagnesium Carbenoids with Nucleophiles
M
ulti-Substitute
s
d Cyclob
u
a
nd A
y
lkylidenecyc
o
lobutane
s
shi Satoh,* Takashi Kasuya, Masashi Ishigaki, Mio Inumaru, Toshifumi Miyagawa, Nobuhito Nakaya,
Shimpei Sugiyama
Graduate School of Chemical Sciences and Technology, Tokyo University of Science, Ichigaya-Funagawara-machi 12, Shinjuku-ku,
Tokyo 162-0826, Japan
Fax +81(3)52614631; E-mail: tsatoh@rs.kagu.tus.ac.jp
Received 18 October 2010; revised 25 November 2010
–78 °C for at least 30 minutes. When this reaction was
Abstract: Treatment of 1-chlorocyclobutyl p-tolyl sulfoxides with
carried out with excess R2MgCl, carbenoids 2 were alkyl-
ated with the Grignard reagents to give the alkylated cy-
clobutylmagnesium chloride intermediates 3, which could
Grignard reagents such as ethylmagnesium chloride, isopropylmag-
nesium chloride, and cyclopentylmagnesium chloride in THF at low
temperature gave cyclobutylmagnesium carbenoids in high yields.
The generated magnesium carbenoids were found to be stable at be trapped with electrophiles to give multi-substituted cy-
–78 °C for at least 30 minutes. The cyclobutylmagnesium car-
benoids reacted with several nucleophiles to give multi-substituted
cyclobutanes. The reaction of the cyclobutylmagnesium carbenoids
alkyllithiums and N-lithioarylamines to give cyclobutanes
with lithium a-sulfonyl carbanions afforded alkylidenecyclobu-
tanes in moderate to good yields.
clobutanes 4 in moderate to good yields. Cyclobutylmag-
nesium carbenoids 2 were proved to be reactive with some
5. The reaction of 2 with lithium a-sulfonyl carbanions
gave alkylidenecyclobutanes 6 in moderate to good
Key words: cyclobutane, alkylidenecyclobutane, magnesium car-
yields. Details of the aforementioned results are reported
benoid, cyclobutylmagnesium carbenoid, cyclobutylmagnesium
in this paper.
chloride
R1
R1
Cl
R1
R1
Cl
R1
R1
MgCl
R2
R2MgCl
R2MgCl
Although cyclobutane skeletal structures are not widely
found in natural products, cyclobutane derivatives are
quite interesting compounds. Due to high angular and tor-
sional strain, cyclobutanes are fairly reactive under a vari-
ety of conditions and often used as versatile intermediates
in organic synthesis.1 Cyclopropanes are another small-
ring compounds having inherent ring strain comparable to
that of cyclobutanes and have been widely studied in or-
ganic chemistry; however, the chemistry of cyclobutanes
is not fully investigated even now.
STol
MgCl
O
2
3
1
electrophile
(E+)
R1
R1
E
3
2
R2
4
R3Li
R1
R1
H
R3
We have been interested in the chemistry of cyclopro-
panes, especially cyclopropylmagnesium carbenoids (cy-
clopropanes bearing magnesium and chlorine atoms at the
same carbon) generated from 1-chlorocyclopropyl p-tolyl
sulfoxides with Grignard reagents, and many interesting
properties of the carbenoids have been unveiled.2 In con-
tinuation of our interest in the chemistry of small-ring
magnesium carbenoids, we recently started to investigate
the generation, property, and synthetic uses of cyclobutyl-
magnesium carbenoids, which delivered quite interesting
results.3
5
R4R5CSO2Ph
Li
R4
R5
R1
R1
6
Scheme 1
Synthesis of 1-Chlorocyclobutyl p-Tolyl Sulfoxides
Three 1-chlorocyclobutyl p-tolyl sulfoxides 1a–c were se-
lected, which are the precursors for the generation of cy-
clobutylmagnesium carbenoids 2, and synthesized them
as follows (Scheme 2). Alkylation of the two hydroxy
groups of known diol 75 with 3-phenylpropyl bromide fol-
lowed by catalytic hydrogenation and oxidation with IBX
in DMSO gave cyclobutanone 8 in high overall yields.
Reductive thiolation of cyclobutanone 8 with 4-methyl-
benzenethiol under Fyfe’s conditions6 gave cyclobutyl p-
tolyl sulfide 9 in quantitative yield. Oxidation of the sul-
fide 9 with MCPBA followed by chlorination of the re-
Thus, as shown in Scheme 1, treatment of 1-chlorocy-
clobutyl p-tolyl sulfoxides 1 with Grignard reagents
(R2MgCl) in THF at low temperature afforded cyclobutyl-
magnesium carbenoids 2 in high yields via the sulfoxide–
magnesium exchange reaction.4 The generated cyclobu-
tylmagnesium carbenoids 2 were found to be stable at
SYNTHESIS 2011, No. 3, pp 0397–0408
x
x
.
x
x
.2
0
1
1
Advanced online publication: 10.01.2011
DOI: 10.1055/s-0030-1258391; Art ID: F18310SS
© Georg Thieme Verlag Stuttgart · New York

398
T. Satoh et al.
PAPER
sulting sulfoxide with NCS gave the desired 1-
chlorocyclobutyl p-tolyl sulfoxide 1a in quantitative
yield. When the alkylation of diol 7 was carried out with
iodoethane, 1-chlorocyclobutyl p-tolyl sulfoxide 1b was
obtained in a similar overall yield as that of 1a.
Table 1 Conditions for the Intramolecular Alkylation of 10 to Cy-
clobutyl p-Tolyl Sulfoxide (11)
O
O
STol
base
STol
TsO
THF, conditions
10
11
1) NaH, Ph(CH2)3Br
DMF, 97%
HO
HO
Ph(CH2)3O
Ph(CH2)3O
OBn
O
Entry Base
Concn Conditions
(mol/L)
11,
Yield (%)
2) H2, Pd/C, EtOAc
99%
3) IBX, DMSO, 99%
7
8
1
2
LDA (2 equiv)
0.2
–78 °C to r.t.
–78 °C to r.t.
–78 °C to r.t.
–78 °C to r.t.
–78 °C to r.t.
–78 °C to r.t.
–78 °C to r.t.
–78 °C to r.t.
0 °C, 1 h
68
74
78
80
56
24
54
80
92
RO
RO
9
1) MCPBA
TolSH, Et3SiH
TFA, CHCl3, 99%
STol
LDA (2 equiv)
LDA (2 equiv)
LDA (2 equiv)
LDA (1.5 equiv)
NaH (2 equiv)
0.1
2) NCS
2 steps, 99%
3
0.05
0.025
0.025
0.025
Ph(CH2)3O
Cl
4
EtO
EtO
Cl
Ph(CH2)3O
S
Tol
S
Tol
5
O
O
1a
1b
6
1) TolSH, NaOEt, EtOH, 92%
2) TsCl, Et3N, toluene, 91%
7
LiHMDS (2 equiv) 0.025
KHMDS (2 equiv) 0.025
Cl
HO
8
3) MCPBA, CH2Cl2, –78 °C to r.t., 90%
9
LDA (2 equiv)
LDA (2 equiv)
0.025
0.025
LDA (2 equiv), 0.025 mol/L
THF, 0 °C to r.t., then 1 h
98%
S
Tol
S
Tol
TsO
10
0 °C to r.t., 1 h; 98
then r.t. ,1 h
O
O
10
NCS
THF
0 °C to r.t.
99%
11
(80%; compare the yields in entries 4 and 8). Fortunately,
when this reaction was carried out at 0 °C for 1 h, much
better yield (92%) was obtained (entry 9). Finally, the
conditions shown in entry 10 were selected as the condi-
tions of choice for this reaction. Chlorination of 11
smoothly proceeded with NCS in THF at room tempera-
ture to give 1-chlorocyclobutyl p-tolyl sulfoxide (1c) in
quantitative yield.
Cl
S
Tol
O
1c
Scheme 2 Synthesis of 1-chlorocyclobutyl p-tolyl sulfoxides 1a–c
As cyclobutanone itself is very expensive, the desired 1-
chlorocyclobutyl p-tolyl sulfoxide (1c) was synthesized
from much less expensive starting material. Thus, 4-chlo-
robutan-1-ol was treated with sodium 4-methylbenzene-
thiolate and the hydroxy group in the resultant sulfide was
tosylated7 to give tosyloxy sulfide in high yield. The sul-
fur of the sulfide was oxidized with MCPBA to afford to-
syloxy sulfoxide 10 in good yield. Next, the conditions for
the intramolecular alkylation of 10 were investigated and
the results are summarized in Table 1.
Generation and Property of Cyclobutylmagnesium
Carbenoids
In our previous study,2h,i we could generate cyclopropyl-
magnesium carbenoids from 1-chlorocyclopropyl p-tolyl
sulfoxides with i-PrMgCl via the sulfoxide–magnesium
exchange reaction.4 Based on these experiences, 1-chloro-
cyclobutyl p-tolyl sulfoxide 1a was treated with 2.5
equivalents of i-PrMgCl in THF at –78 °C for 10 minutes
and the reaction was quenched with MeOD (Table 2, en-
try 1). A clean reaction mixture was obtained, in which all
the starting material 1a had disappeared. Deuterated chlo-
rocyclobutane 12 was obtained in 84% yield with perfect
deuterium incorporation. This result implied that the sul-
foxide–magnesium exchange reaction of 1a took place in-
stantaneously with i-PrMgCl even at –78 °C to afford the
At first, 10 was treated with 2 equiv of LDA in THF (con-
centration of the reaction mixture: 0.2 mol/L) at –78 °C
and the temperature of the reaction mixture was allowed
to warm to room temperature (Table 1, entry1). Fortunate-
ly, the desired cyclobutyl p-tolyl sulfoxide 11 was ob-
tained in 68% yield with some unknown by-products.
Next, the reaction was conducted in dilute conditions (en- desired cyclobutylmagnesium carbenoid 2a in high yield.
tries 2–4) and the yield of 11 was improved up to 80%.
Reducing the amount of LDA to 1.5 equiv was found to
be less effective (entry 5). Sodium hydride and lithium
Generation of cyclobutylmagnesium carbenoid 2a from
1a was carried out with other Grignard reagents and the
results are summarized in Table 2, entries 2 to 5. Interest-
hexamethyldisilazide (LiHMDS) were also found to be
ingly, methylmagnesium chloride was found to be totally
less effective in this reaction (entries 6 and 7). Only potas-
ineffective to the sulfoxide–magnesium exchange reac-
sium hexamethyldisilazide (KHMDS) was proved to be
tion (entry 2). Ethylmagnesium chloride proved to be the
effective to give 11 in the same yield as that with LDA
best Grignard reagent (entry 3). Cyclopentylmagnesium
Synthesis 2011, No. 3, 397–408 © Thieme Stuttgart · New York

PAPER
Multi-Substituted Cyclobutanes and Alkylidenecyclobutanes
399
chloride was found to be effective in this reaction; howev-
er, phenylmagnesium chloride was not (entries 4 and 5).
tert-Butylmagnesium chloride also was totally ineffective
in this sulfoxide–magnesium exchange reaction.
Table 2 Generation of Cyclobutylmagnesium Carbenoid 2a from
1a and Quenching with MeOD
Grignard
reagent
Ph(CH2)3OCH2
Ph(CH2)3OCH2
Cl
R
R
Cl
(2.5 equiv)
In order to investigate the stability of cyclobutylmagne-
sium carbenoid 2a, the sulfoxide 1a was treated with eth-
ylmagnesium chloride under various temperature and
time, and the reaction was quenched with MeOD. The sta-
bility of cyclobutylmagnesium carbenoid 2a was estimat-
ed from the chemical yield and deuterium content of the
product 12. The results are summarized in Table 2, entries
6–16. Entry 6 shows that the sulfoxide–magnesium ex-
change reaction of 1a instantaneously proceeds even at
–90 °C. From the results in entries 7 and 8, it is implied
that the generated cyclobutylmagnesium carbenoid 2a is
stable at lower than –78 °C for at least 30 minutes. It is
worth noting that cyclobutylidene derived from 1,1-dibro-
mocyclobutane with methyllithium or diazocyclobutane
was reported to be highly reactive and gave rearranged
products such as methylenecyclopropane, cyclobutene,
and buta-1,3-diene.8 In contrast to this, cyclobutylmagne-
sium carbenoid 2a is proved to be quite stable and the re-
arranged products were not observed in our cases.
THF
STol
MgCl
2a
1a
O
R
Cl
D
MeOD
R = Ph(CH2)3OCH2
R
12
Entry Grignard reagent Temp (°C) Time (min) 12, Yield (%)
1
2
i-PrMgCl
MeMgCl
EtMgCl
c-PentMgCl
PhMgCl
EtMgCl
EtMgCl
EtMgCl
EtMgCl
EtMgCl
EtMgCl
EtMgCl
EtMgCl
EtMgCl
EtMgCl
EtMgCl
–78
–78
–78
–78
–78
–90
–90
–78
–78
–70
–70
–60
–60
–50
–50
–40
10
10
10
10
10
10
30
30
60
10
30
10
30
10
30
10
84a
no reaction
90a
3
4
79a
5
trace
94a
6
7
88a
8
86a
When this reaction was carried out at higher temperature,
the yield of 12 was gradually diminished (entries 10–13).
Interestingly, when this reaction was carried out at –50 °C
or higher, ethylated cyclobutane 13 was obtained as a by-
product (entries 14–16). These results implied that mag-
nesium carbenoid 2a is prone to react with Grignard re-
agents and the intermediate of this reaction is ethylated
cyclobutylmagnesium chloride 14 (R1 = Et; see Table 3).
9
83a
10
11
12
13
14
15
16
81a
78a
80a
72a
Reaction of 1-Chlorocyclobutyl p-Tolyl Sulfoxides
with Excess Grignard Reagents Followed by Electro-
philes: Synthesis of Multi-Substituted Cyclobutanes
with Two Carbon–Carbon Bond Formation in One-
Pot
57a,b
48a,c
40a,d
From the viewpoint of organic synthesis, alkylation of cy-
clobutylmagnesium carbenoids with carbanions is very
interesting. As mentioned above, we found that cyclobu-
tylmagnesium carbenoid 2a reacted with ethylmagnesium
chloride to afford ethylated cyclobutane 13 (see Table 2,
footnote). The intermediate of this reaction was expected
to be the ethylated cyclobutylmagnesium chloride 14
(R1 = Et; see Table 3). If this intermediate 14 can be
trapped with carbon electrophiles, multi-substituted cy-
clobutane derivatives bearing a quaternary carbon 15
would be synthesized. We brought this plan in practice
and the results are summarized in Table 3.
a D-content over 99%.
b About 20% of ethylated cyclobutane 13 was obtained as a by-prod-
uct.
R
Et
D
R
13
c About 30% of 13 was obtained.
d About 40% of 13 was obtained
(R1 = Et, E = Me) was obtained in 69% yield (entry 2).
Allylated product 15c was obtained in 64% yield by the
same treatment with allyl iodide (entry 3). Benzoylation
of the intermediate 14 was also found to be successful un-
der the same conditions described above to give cyclobu-
tane bearing a quaternary carbon 15d in 60% yield (entry
4). The reaction with ethyl chloroformate gave the desired
product; however, the yield was moderate (entry 5). The
addition reaction of the carbanion intermediate 14 with
benzaldehyde did not proceed at all (entry 6).
Thus, 1-chlorocyclobutyl p-tolyl sulfoxide 1a was treated
with 5 equivalents of ethylmagnesium chloride in THF at
–90 °C and the temperature of the reaction mixture was
slowly allowed to warm to 0 °C. When this reaction was
quenched with water, ethylated cyclobutane 15a (R1 = Et,
E = H) was produced in 76% yield (Table 3, entry 1).
When this reaction was treated with 5 equivalents of io-
domethane in the presence of 10 mol% of Cu(I) iodide2h
at 0 °C for one hour, dialkylated cyclobutane 15b
Synthesis 2011, No. 3, 397–408 © Thieme Stuttgart · New York

400
T. Satoh et al.
PAPER
results are summarized in Table 4. Thus, cyclobutylmag-
nesium carbenoid 2a, which was generated from 1a with
2.5 equivalents of EtMgCl in THF at –90 °C, was treated
with 3 equivalents of lithium acetylide derived from phe-
nylacetylene with n-BuLi and the temperature of the reac-
tion mixture was slowly allowed to warm to 0 °C
(Table 4, entry 1). Interestingly, an inseparable mixture of
cyclobutylacetylene 16a and allene 16b (the ratio of 16a/
16b = 3:10) was obtained in 78% yield. When this reac-
tion was conducted with lithium acetylide derived from 4-
fluorophenylacetylene, an inseparable mixture of 16c and
16d (the ratio of 16c/16d = 9:10) was produced in 47%
yield (entry 2). In both reactions, allene (16b and 16d, re-
spectively) was the main product. We attempted to obtain
allene 16b as the single product; however, any effort to
change the ratio in favor of the allene was fruitless.
Table 3 Reaction of 1-Chlorocyclobutyl p-Tolyl Sulfoxide 1a with
Excess Grignard Reagent Followed by Electrophiles to Afford Multi-
Substituted Cyclobutanes 15
Ph(CH2)3OCH2
Ph(CH2)3OCH2
R1MgCl
Cl
R
R
Cl
THF
–90 to 0 °C
STol
MgCl
2a
1a
O
electrophile
(E+)
R1MgCl
R
R
R
E
MgCl
R1
R1
0 °C, 1 h
R
14
15
Entry R1MgCl
Electrophile
Additive 15, Yield (%)
1
2
EtMgCla
EtMgCla
EtMgCla
EtMgCla
EtMgCla
EtMgCla
H2O
none
CuIb
CuIb
CuIb
none
CuIb
none
CuIb
CuIb
CuIb
none
CuIb
CuIb
CuIb
15a, 76
15b, 69
15c, 64
15d, 60
15e, 45
MeI
Table 4 Reaction of Cyclobutylmagnesium Carbenoids 2 with Lith-
ium Acetylides and 2-Lithiothiophenes
3
H2C=CHCH2I
PhCOCl
EtOCOCl
PhCHO
H2O
1) R1Li
THF, –90 to 0 °C
2) H2O
4
R
R
Cl
R
R
H
5
R1
MgCl
c
2a,b
6
–
16
a: R = Ph(CH2)3OCH2
b: R = EtOCH2
7
i-PrMgCld
15f, 72
15g, 74
15h, 72
15i, 33
15j, 77
15k, 70
15l, 75
15m, 51
8
i-PrMgCld
MeI
Entry
2
R1Li
16, Yield (%)
9
i-PrMgCld
H2C=CHCH2I
PhCOCl
H2O
R
R
H
10
11
12
13
14
i-PrMgCld
1
2a
C
CLi (3 equiv)
c-PentMgCld
c-PentMgCld
c-PentMgCld
c-PentMgCld
Ph
MeI
16a
R
H2C=CHCH2I
PhCOCl
Ph
R
16b
a Five equiv of EtMgCl was used.
b Ten mol% of CuI was used.
16a/16b = 3:10 (78)
R
H
c Ethylated cyclobutane 15a was obtained as the main product.
R
d Grignard reagent used: 7.5 equiv.
2
2a
F
C CLi
(3 equiv)
Ar
A similar reaction was proved to be able to carry out with
isopropylmagnesium chloride and cyclopentylmagnesium
chloride (entries 7–14); however, in these reactions, 7.5
equivalents of the Grignard reagents were required in or-
der to give good results. As shown in entries 7–10, isopro-
pylated cyclobutanes 15f–i (R1 = i-Pr) were obtained in
similar yields compared with the corresponding ethylated
products. Interestingly, the reactions with cyclopentyl-
magnesium chloride gave somewhat better yields of the
desired products 15j–m (R1 = cyclopentyl; entries 11–
14).
16c
R
Ar
R
16d
16c/16d = 9:10 (47)
S
Li
3
4
2b
2b
16e (34)
(5 equiv)
Li
S
16f (22)
(5 equiv)
Reaction of Cyclobutylmagnesium Carbenoids with
Lithium Acetylides, 2-Lithiothiophenes, N-Lithio-N-
methylarylamines and N-Lithiophenothiazine
The mechanism of this interesting reaction was presumed
to be as follows (Scheme 3). Thus, SN2 like substitution
reaction of magnesium carbenoid 2a with lithium acetyl-
ide gave cyclobutylmagnesium chloride intermediate 17.
This propargylic carbanion then rearranged to allenic
carbanion 18.10 Carbanions 17 and 18 must be present in
We have previously reported the reaction of magnesium
alkylidenecarbenoids with lithium acetylides.9 Based on
this experience, the reaction of cyclobutylmagnesium car-
benoids with lithium acetylides was investigated and the
Synthesis 2011, No. 3, 397–408 © Thieme Stuttgart · New York

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Multi-Substituted Cyclobutanes and Alkylidenecyclobutanes
401
Table 5 Reaction of Cyclobutylmagnesium Carbenoids 2 with
N-Lithio-N-methylarylamines and N-Lithiophenothiazine
MgCl
R
R
MgCl
R
R
Cl
R
R
MgCl
Ph
N(Li)Me
18
Ph
+
17
C
C
Ph
2a
(3 equiv)
R
R
R
Cl
R
R
H
H
R
R
R
R
H
protonation
THF–HMPA
–78 to –20 °C
MgCl
NMe
Ph
2a,c
16b
Ph
16a
R
a: R = Ph(CH2)3OCH2
c: R = H
Scheme 3 A plausible mechanism for the formation of 16a and 16b
by the reaction of cyclobutylmagnesium carbenoid 2a with lithium
acetylide derived form phenylacetylene
19
19
Entry
1
2
N-Lithioarylamine
Yield (%)
35
equilibrium and they are protonated in the reaction medi-
um to afford acetylene 16a and allene 16b.
N(Li)Me
2c
19a
19b
19c
19d
We have also previously reported the reaction of magne-
sium alkylidenecarbenoids with 2-lithiothiophenes to give
2-alkenylated thiophenes in good yields.11 Based on this
study, the reaction of cyclobutylmagnesium carbenoid 2b
with 2-lithiothiophenes was investigated (Table 4, entries
3 and 4). Thus, carbenoid 2b generated from 1b with 2.5
equivalents of EtMgCl in THF at –90 °C was treated with
5 equivalents of 2-lithiothiophenes, which were derived
from thiophenes with n-BuLi, and the temperature of the
reaction mixture was slowly allowed to warm to 0 °C. The
desired 2-cyclobutylthiophenes 16e and 16f were ob-
tained; however, the yields were very low compared to
those from the reaction with magnesium alkylidene car-
benoids.11
N(Li)Me
2
3
4
2c
2c
2c
32
31
28
MeO
Cl
N(Li)Me
N(Li)Me
N(Li)Me
5
6
2c
2a
19e
20
34
40
Li
N
Finally, the reaction of cyclobutylmagnesium carbenoid 2
with nitrogen nucleophiles was investigated (Table 5).12
Thus, carbenoid 2c generated from 1c with 2.5 equiva-
lents of EtMgCl in THF at –78 °C was treated with 3
equivalents of N-lithio-N-methylaniline, which was gen-
erated from N-methylaniline with n-BuLi, and the temper-
ature of the reaction mixture was slowly allowed to warm
to –20 °C. The desired N-cyclobutyl-N-methylaniline
(19a) was obtained; however, the yield was only 35%.
The results of the reaction with N-methyl-4-substituted
anilines and N-methyl-1-naphthylamine are summarized
in entries 2–5. These reactions gave the desired products
in up to 34%. The reaction of cyclobutylmagnesium car-
benoid 2a with N-lithiophenothiazine gave N-cyclobu-
tylphenothiazine 20 in somewhat better yield (entry 6).
S
Thus, at first, cyclobutylmagnesium carbenoid 2a was
generated from 1a with 2.5 equivalents of EtMgCl at
–78 °C in THF. In an another flask, a solution of lithium
a-sulfonyl carbanion of benzyl phenyl sulfone was pre-
pared from benzyl phenyl sulfone and n-BuLi at 0 °C and
it was transferred to the solution of 2a through a cannula
and the temperature of the reaction mixture was slowly al-
lowed to warm to –20 °C to afford benzylidenecyclobu-
tane 6a (Table 6, entry 1) in 83% yield. Other examples
for the reaction of 2a with various lithium a-sulfonyl car-
banions are summarized in entries 2 to 8 in Table 6. Gen-
erally, the yields were better when the sulfonyl carbanions
have an aromatic group or a conjugated unsaturated group
(entries 1–5). Alkylidenecyclobutanes bearing a fully sub-
stituted olefinic group, 6c and 6h, also could be synthe-
sized by this procedure (entries 3 and 8). The reaction
starting from 1-chlorocyclobutyl p-tolyl sulfoxide (1c) via
cyclobutylmagnesium carbenoid 2c gave the desired alky-
lidenecyclobutanes 6i–k in similar yields (entries 9–11).
Synthesis of Alkylidenecyclobutanes by the Reaction
of Cyclobutylmagnesium Carbenoids with Lithium a-
Sulfonyl Carbanions
Alkylidenecyclobutanes are quite interesting compounds
in synthetic organic chemistry.13 In our previous studies,
we have reported the reaction of magnesium carbenoids,
magnesium alkylidenecarbenoids, and cyclopropylmag-
nesium carbenoids with lithium a-sulfonyl carbanions to
give olefins,14 allenes,15 and alkylidenecyclopropanes,2b
respectively. These reactions were applied to the cyclobu-
tylmagnesium carbenoids 2 and indeed we could obtain
the desired alkylidenecyclobutanes 6 in moderate to good
yields. The results are summarized in Table 6.
In conclusion, we have found that the reaction of 1-chlo-
rocyclobutyl p-tolyl sulfoxides with Grignard reagents,
especially EtMgCl, at low temperature gave cyclobutyl-
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402
T. Satoh et al.
PAPER
CaH2 for use in experiments requiring an anhyd reagent. THF was
distilled from diphenylketyl and acetone was dried over CaSO4 and
distilled before use. Benzaldehyde, benzoyl chloride, and ethyl
chloroformate were distilled before use.
Table 6 Synthesis of Alkylidenecyclobutanes 6 from 1-Chlorocy-
clobutyl p-Tolyl Sulfoxides 1 and Lithium a-Sulfonyl Carbanions via
Cyclobutylmagnesium Carbenoids 2
EtMgCl
R
R
Cl
R
R
Cl
(2.5 equiv)
3,3-Bis(3-phenylpropoxymethyl)cyclobutanone (8)
THF, –78 °C
STol
MgCl
A solution of 7 (0.44 g, 2 mmol) in anhyd DMF (3 mL) was added
to a suspension of NaH (0.35 g, 8 mmol) in anhyd DMF (17 mL) at
0 °C. After stirring the reaction mixture for 1 h, 3-phenylpropyl bro-
mide (1.2 mL, 8 mmol) was added. The mixture was stirred for 2 h
and the reaction was quenched by the addition of sat. aq NH4Cl (1
mL) at 0 °C. The mixture was extracted with benzene (3 × 100 mL)
(Caution! Benzene has been identified as a carcinogen. All proce-
dures involving benzene should be carried out in a well-ventilated
hood, and glove protection is required). The combined organic lay-
ers were washed with sat. aq NH4Cl (100 mL) and dried (MgSO4).
The solvent was evaporated under vacuum to give a residue, which
was purified by silica gel column chromatography (hexane–EtOAc)
to give the intermediate ether (0.89 g, 97%) as a colorless oil. To a
solution of the intermediate ether (0.80 g, 1.74 mmol) in EtOAc (9
mL) was added 10% Pd/C (0.16 g, 20%wt). The reaction mixture
was stirred under H2 atmosphere for 12 h. The mixture was filtered
and the solvent was evaporated under vacuum to give a residue,
which was purified by silica gel column chromatography (hexane–
EtOAc) to give the intermediate alcohol (0.63 g, 99%) as a colorless
oil. IBX (0.58 g, 2.08 mmol) was added to a solution of the alcohol
(0.64 g, 1.73 mmol) in DMSO (8 mL) and the reaction mixture was
stirred for 2 h at r.t. The mixture was extracted with benzene (2 × 50
mL) (Caution! see above) and the combined organic layers were
washed with H2O (3 × 50 mL) and dried (MgSO4). The solvent was
evaporated under vacuum to give a residue, which was purified by
silica gel column chromatography (hexane–EtOAc) to give 8 (0.65
g, 99%) as a colorless oil.
O
2
1a R = Ph(CH2)3OCH2
1c R = H
R2R3CSO2Ph
R2
R3
(3 equiv)
Li
R
R
conditions
6
Entry
1
Sulfone
R2
Conditions
6, Yield (%)
R3
H
1
2
3
4
5
6
1a
1a
1a
1a
1a
1a
Ph
–78 to –20 °C
–78 to –20 °C
–78 to –20 °C
–78 to –20 °C
–78 to –20 °C
6a, 83
6b, 76
6c, 71
6d, 77
6e, 67
1-naphthyl
Ph
H
Me
H
H2C=CH
MeC≡C
H
H
H
–78 to –50 °C, 6f, 56
then 3 h
7
8
1a
1a
Me
Me
H
–78 to –50 °C, 6g, 47
then 3 h
Me
–78 to –50 °C, 6h, 49
then 3 h
IR (neat): 3026, 2930, 2860, 2797, 1785 (C=O), 1603, 1497, 1454,
1376, 1115, 924, 818 cm–1.
1H NMR: d = 1.88 (4 H, quint, J = 6.3 Hz), 2.68 (4 H, t, J = 7.7 Hz),
2.91 (4 H, s), 3.47 (4 H, t, J = 6.3 Hz), 3.53 (4 H, s), 7.16–7.19 (6
H, m), 7.25–7.29 (4 H, m).
MS: m/z (%) = 366 (M+, 8), 248 (8), 118 (98), 91 (100).
HRMS: m/z calcd for C24H30O3 (M+): 366.2195; found: 366.2192.
9
10
11
1c
1c
1c
Ph
H
–78 to –20 °C
–78 to –20 °C
–78 to –20 °C
6i, 78
6j, 70
6k, 64
1-naphthyl
Ph
H
Me
magnesium carbenoids in high yields. The generated cy-
clobutylmagnesium carbenoids were found to be stable at
–78 °C for at least 30 minutes. Multi-substituted cyclobu-
tanes were synthesized in moderated to good yield based
on the reaction of the cyclobutylmagnesium carbenoids
with carbanions and N-lithioarylamines. Alkylidenecy-
clobutanes were synthesized by the reaction of cyclobu-
tylmagnesium carbenoids with lithium a-sulfonyl
carbanions in moderate to good yields. The chemistry pre-
sented here is unprecedented and will contribute to the
synthesis of cyclobutane derivatives.1
1,1-Bis(3-phenylpropoxymethyl)-3-(p-tolylsulfanyl)cyclobu-
tane (9)
TFA (4.1 mL) was added slowly to a stirred solution of cyclobu-
tanone 8 (0.61g, 1.65 mmol) and p-toluenethiol (0.23g, 1.82 mmol)
in CHCl3 (4.1 mL) keeping at r.t. Et3SiH (1.3 mL, 8.25 mmol) was
then added to the reaction mixture over 5 min, again ensuring that
the internal temperature stayed below r.t. The mixture was stirred at
r.t. for 6 h and partitioned between CHCl3 (50 mL) and H2O (50
mL). The aqueous phase was further extracted with CHCl3 (50 mL)
and the combined organic extracts were washed with H2O (80 mL),
sat. aq Na2CO3 (80 mL) and H2O (80 mL), and dried (MgSO4). Fil-
tration, solvent removal, and flash chromatography (hexane–
EtOAc) furnished the compound 9 (0.80 g, 99%) as a colorless oil.
IR (neat): 3025, 2930, 2858, 2793, 1602, 1494, 1455, 1367, 1113,
923 cm–1.
All melting points were measured on Yanaco MP-S3 apparatus and
are uncorrected. H NMR spectra were recorded on Jeol JNMLA
1
1H NMR: d = 1.83–1.92 (4 H, m), 1.96–2.00 (2 H, m), 2.30 (3 H, s),
2.34–2.43 (2 H, m), 2.65–2.70 (4 H, m), 3.35 (2 H, s), 3.40 (2 H, t,
J = 6.3 Hz), 3.43 (2 H, s), 3.46 (2 H, t, J = 6.3 Hz), 3.79 (1 H, quint,
J = 8.1 Hz), 7.07–7.09 (2 H, m), 7.17–7.19 (8 H, m), 7.25–7.29 (4
H, m).
MS: m/z (%) = 474 (M+, 62), 150 (100), 135 (14), 118 (16), 91 (63).
HRMS: m/z calcd for C31H38O2S (M+): 474.2593; found: 474.2593.
500 and Bruker XWIN-600 spectrometers in CDCl3 solution. Elec-
tron-impact mass spectra (MS) were obtained at 70 eV by direct in-
sertion by Hitachi M-80B mass spectrometer. IR spectra were
recorded on a Perkin-Elmer Spectrum One FT-IR instrument. Silica
gel 60N (Kanto Chemical) containing 0.5% fluorescence reagent
254 and a quartz column were used for column chromatography and
the products having UV absorption were detected by UV irradia-
tion. CH2Cl2, i-Pr2NH, Et3N, DMF, and HMPA were distilled from
Synthesis 2011, No. 3, 397–408 © Thieme Stuttgart · New York

PAPER
Multi-Substituted Cyclobutanes and Alkylidenecyclobutanes
403
1-Chloro-3,3-bis(3-phenylpropoxymethyl)-1-(p-tolylsulfi-
nyl)cyclobutane (1a)
(70%, 2.47 g, 10 mmol) and the mixture was stirred for 2 h. The re-
action was quenched with sat. aq Na2SO3 (2 mL) and the mixture
was diluted with CH2Cl2 (20 mL). The mixture was extracted with
CH2Cl2 (2 × 20 mL) and the combined organic layers were washed
with 5% NaOH (2 × 60 mL) followed by sat. aq NH4Cl (100 mL).
The organic layer was dried (MgSO4) and the solvent was evaporat-
ed. The product was purified by silica gel column chromatography
(hexane–EtOAc) to afford 3.20 g (96%) of sulfoxide 10 as colorless
crystals; mp 48–49 °C (hexane–EtOAc).
A solution of sulfide 9 (4.86 g, 10.2 mmol) in CHCl3 (40 mL) was
cooled to –78 °C. To this solution was added m-chloroperbenzoic
acid (75%, 2.69 g, 11.7 mmol) and the reaction mixture was stirred
and slowly allowed to warm to 0 °C. The reaction was quenched
with sat. aq Na2SO3 (2 mL) and the mixture was diluted with CHCl3
(30 mL). The organic layer was washed with aq 5% NaOH (2 × 60
mL) followed by sat. aq NH4Cl (60 mL). The organic layer was
dried (MgSO4) and the solvent was evaporated. The product was
purified by silica gel column chromatography (hexane–EtOAc) to
afford 4.96 g (99%) of the sulfoxide as a colorless oil. N-Chlorosuc-
cinimide (1.69 g, 12.7 mmol) was added to a solution of the sulfox-
ide (4.96 g, 10.1 mmol) in anhyd THF (25 mL) and the suspension
was stirred at r.t. for 12 h. The solution was concentrated and the
precipitate (succinimide) was filtered off and the filtrate was evap-
orated to give a residue that was then purified by silica gel column
chromatography (hexane–EtOAc) to afford 5.3 g (99%) of 1a as a
colorless oil.
IR (KBr): 2924, 1598, 1495, 1453, 1357, 1189, 1176, 1088, 1044,
1016, 931, 813 cm–1.
1H NMR: d = 1.65–1.83 (4 H, m), 2.42 (3 H, s), 2.46 (3 H, s), 2.70–
2.75 (2 H, m), 4.00–4.04 (2 H, m), 7.31–7.36 (4 H, m), 7.47 (2 H, d,
J = 8.2 Hz), 7.76 (2 H, d, J = 8.2 Hz).
Anal Calcd for C18H22O4S2: C, 58.66; H, 6.08; S, 17.27. Found: C,
58.99; H, 6.05; O, 17.46; S, 17.50.
Cyclobutyl p-Tolyl Sulfoxide (11)
Sulfoxide 10 (0.73 g; 2.0 mmol) was added dropwise to a solution
of LDA (4 mmol) in anhyd THF (80 mL) at 0 °C with stirring under
argon atmosphere. The reaction mixture was stirred and slowly al-
lowed to warm to r.t., and stirred additionally for 1 h at r.t. The re-
action was quenched with sat. aq NH4Cl (50 mL). The mixture was
extracted with CHCl3 (3 × 50 mL) and the combined organic layers
were dried (MgSO4). The product was purified by silica gel column
chromatography (hexane–EtOAc) to afford 11 (0.38 g, 98%) as a
colorless oil.
IR (neat): 3061, 3026, 2935, 2860, 1599, 1495, 1455, 1407, 1368,
1292, 1178, 1114, 1056, 929 cm–1.
1H NMR: d = 1.84–1.91 (4 H, m), 2.00 (1 H, d, J = 14.2 Hz), 2.41
(3 H, s), 2.46 (1 H, d, J = 14.3 Hz), 2.65–2.70 (4 H, m), 2.87 (1 H,
d, J = 14.4 Hz), 2.98 (1 H, d, J = 14.3 Hz), 3.44–3.49 (6 H, m), 3.59
(2 H, s), 7.15–7.29 (12 H, m), 7.61–7.63 (2 H, m).
MS: m/z (%) = 524 (M+, trace), 385 (12), 119 (49), 91(100).
HRMS: m/z calcd for C31H37ClO3S (M+): 524.2152; found:
524.2150.
IR (neat): 2984, 2943, 1597, 1494, 1266, 1245, 1088, 1046, 811
cm–1.
1-Chloro-3,3-bis(ethoxymethyl)-1-(p-tolylsulfinyl)cyclobutane
(1b)
Compound 1b was similarly prepared as above from the corre-
1H NMR: d = 1.72–1.79 (1 H, m), 1.90–1.97 (2 H, m), 2.10–2.17 (1
H, m), 2.39–2.47 (1 H, m), 2.40 (3 H, s), 2.53–2.61 (1 H, m), 3.43
(1 H, quint, J = 8.3 Hz), 7.27–7.29 (2 H, m), 7.43–7.45 (2 H, m).
MS: m/z (%) = 194 (M+, 53), 140 (87), 92 (41), 91 (28), 55 (100).
HRMS: m/z calcd for C11H14OS (M+): 194.0765; found: 194.0763.
sponding ethoxy-substituted derivative; yield: 98%; colorless oil.
IR (neat): 2975, 2931, 2867, 1597, 1491, 1407, 1377, 1355, 1292,
1178, 1111, 1057, 809 cm–1.
1H NMR: d = 1.14–1.21 (6 H, m), 1.91–1.98 (1 H, m), 2.38–2.49 (1
H, m), 2.41 (3 H, s), 2.83–2.89 (1 H, m), 2.92–2.98 (1 H, m), 3.42–
3.54 (6 H, m), 3.60 (2 H, s), 7.27–7.31 (2 H, m), 7.59–7.64 (2 H, m).
MS: m/z (%) = 345 ([M + H]+, 100), 158 (24), 114 (45), 58 (48).
HRMS: m/z calcd for C17H26ClO3S (M+): 345.1291; found:
1-Chlorocyclobutyl p-Tolyl Sulfoxide (1c)
N-Chlorosuccinimide (0.31 g, 2.35 mmol) was added to a solution
of sulfoxide 11 (0.38 g, 1.96 mmol) in anhyd THF (10 mL) and the
suspension was stirred at r.t. for 12 h. The solvent was evaporated
and the precipitate was collected by filtration. The product was pu-
rified by silica gel column chromatography (hexane–EtOAc) to af-
ford 0.44 g (99%) of 1c as colorless crystals; mp 43–44 °C (hexane–
EtOAc).
345.1289.
4-Tosyloxybutyl p-Tolyl Sulfoxide (10)
To a stirred solution of 4-chlorobutan-1-ol (1.09 g, 10 mmol) in
EtOH (12.5 mL) was added NaOEt (1.09 g, 16 mmol) at 0 °C. A so-
lution of p-toluenethiol (1.86 g, 15 mmol) in EtOH (10 mL) was
added to the solution and the reaction mixture was stirred at r.t. for
12 h. The reaction was quenched by adding sat. aq NH4Cl (100 mL)
and the mixture was extracted with CHCl3 (3 × 80 mL). The com-
bined organic layers were dried (MgSO4) and the product was puri-
fied by silica gel column chromatography to give the sulfanyl
alcohol (1.80 g, 92%) as a colorless oil. TsC1 (2.86 g, 15 mmol) in
toluene (10 mL) was added to a stirred solution of the sulfanyl alco-
hol (1.96 g, 10 mmol), Et3N (3.48 mL, 25 mmol), and Me3N·HC1
(95.6 mg, 1.0 mmol) in toluene (10 mL) at 0 °C. The reaction mix-
ture was stirred and slowly allowed to warm to r.t., and stirred for
an additional 1 h. H2O (100 mL) was added to the mixture and it was
extracted with EtOAc (3 × 50 mL). The combined organic layers
were washed with H2O (60 mL) and brine (100 mL), dried
(MgSO4), and concentrated. The obtained crude product was puri-
fied by silica gel column chromatography (hexane–EtOAc) to give
the desired tosylate (3.19 g, 91%) as a colorless oil. A solution of
the tosylate (3.19 g, 9.1 mmol) in CH2Cl2 (36 mL) was cooled to
0 °C. To this solution was added slowly m-chloroperbenzoic acid
IR (KBr): 2955, 2917, 1593, 1489, 1417, 1298, 1254, 1221, 1084,
1054, 913, 810 cm–1.
1H NMR: d = 1.90–2.04 (2 H, m), 2.18–2.30 (1 H, m), 2.42 (3 H, s),
2.40–2.52 (1 H, m), 2.98–3.17 (2 H, m), 7.30 (2 H, d, J = 8.1 Hz),
7.63 (2 H, d, J = 8.1 Hz).
Anal Calcd for C11H13ClOS: C, 57.73; H, 5.68; Cl, 15.37; S, 13.84.
Found: C, 57.76; H, 5.68; Cl, 15.50; O, 6.99; S, 14.02.
1-Chloro-1-deuterio-3,3-bis(3-phenylpropoxymethyl)cyclobu-
tane (12)
A solution of EtMgCl (2.0 M solution in THF, 0.25 mL, 0.5 mmol)
was added to a solution of 1a (105 mg, 0.2 mmol) in of THF (2 mL)
at –78 °C with stirring under argon atmosphere. The solution was
stirred for 10 min and the reaction was quenched with MeOD (0.3
mL) followed by sat. aq NH4Cl (50 mL). The mixture was extracted
with CHCl3 (3 × 20 mL) and the combined organic layers were dried
(MgSO4). The solvent was evaporated and the residue was purified
by silica gel column chromatography (hexane–EtOAc) to afford 12
(69.6 mg, 90%) as a colorless oil.
Synthesis 2011, No. 3, 397–408 © Thieme Stuttgart · New York

404
T. Satoh et al.
PAPER
1-Allyl-1-ethyl-3,3-bis(3-phenylpropoxymethyl)cyclobutane
IR (neat): 3027, 2941, 2859, 1944, 1871, 1803, 1603, 1496, 1455,
1367, 1180, 1112, 921, 820 cm–1.
(15c)
Colorless oil.
1H NMR: d = 1.84–1.96 (4 H, m), 2.20–2.30 (2 H, m), 2.46–2.58 (2
H, m), 2.62–2.75 (4 H, m), 3.35 (2 H, s), 3.39 (2 H, s), 3.40–3.47 (4
H, m), 7.12–7.32 (10 H, m).
MS: m/z (%) = 387 (M+, trace), 118 (100), 91 (58).
HRMS: m/z calcd for C24H30DClO2 (M+): 387.20755; found:
IR (neat): 2923, 2855, 1639, 1603, 1496, 1455, 1366, 1112 cm–1.
1H NMR: d = 0.76 (3 H, t, J = 7.4 Hz), 1.48 (2 H, q, J = 7.4 Hz),
1.61 (2 H, d, J = 12.6 Hz), 1.68 (2 H, d, J = 12.6 Hz), 1.81–1.94 (4
H, m), 2.22 (2 H, d, J = 7.2 Hz), 2.62–2.72 (4 H, m), 3.37–3.46 (8
H, m), 4.94–5.06 (2 H, m), 5.65–5.79 (1 H, m), 7.15–7.29 (10 H, m).
MS: m/z (%) = 420 (M+, 10), 284 (4), 242 (13), 118 (100), 91 (96).
HRMS: m/z calcd for C29H40O2 (M+): 420.3028; found: 420.3027.
387.2076.
1-Deuterio-1-ethyl-3,3-bis(3-phenylpropoxymethyl)cyclobu-
tane (13)
This compound was isolated from the reaction of 1a with EtMgCl
conducted as above, but at –40 °C or –50 °C (see, Table 2); color-
less oil.
[1-Ethyl-3,3-bis(3-phenylpropoxymethyl)cyclobutyl]phenyl-
methanone (15d)
Colorless oil.
IR (neat): 3026, 2952, 2926, 2854, 1603, 1497, 1455, 1366, 1112,
745, 699 cm–1.
1H NMR: d = 0.79 (3 H, t, J = 7.4 Hz), 1.39 (2 H, q, J = 7.3 Hz),
1.45–1.54 (2 H, m), 1.81–1.97 (6 H, m), 2.68 (4 H, t, J = 7.4 Hz),
3.31 (2 H, s), 3.37–3.51 (6 H, m), 7.12–7.34 (10 H, m).
MS: m/z (%) = 381 (M+, 8), 118 (100), 91 (80).
HRMS: m/z calcd for C26H35DO2 (M+): 381.2778; found: 381.2777.
IR (neat): 2932, 2859, 1714, 1674 (C=O), 1455, 1239, 1113, 911
cm–1.
1H NMR: d = 0.67 (3 H, t, J = 7.4 Hz), 1.74–1.83 (2 H, m), 1.88–
1.97 (2 H, m), 2.10–2.17 (4 H, m), 2.56–2.64 (4 H, m), 2.70–2.75 (2
H, m), 3.23 (2 H, s), 3.33 (2 H, t, J = 6.3 Hz), 3.42 (2 H, s), 3.49 (2
H, t, J = 6.3 Hz), 7.10–7.31 (10 H, m), 7.39–7.44 (2 H, m), 7.48–
7.54 (1 H, m), 7.87–7.90 (2 H, m).
MS: m/z (%) = 484 (M+, 40), 319 (13), 243 (18), 118 (100), 91 (98),
1-Ethyl-3,3-bis(3-phenylpropoxymethyl)cyclobutane (15a)
A solution of EtMgCl (2.0 M solution in THF, 0.5 mL, 1.0 mmol)
was added to a solution of 1a (105 mg, 0.2 mmol) in THF (2 mL) at
–90 °C with stirring under argon atmosphere. The reaction mixture
was stirred and slowly allowed to warm to 0 °C. The reaction was
quenched by adding sat. aq NH4Cl (50 mL) and the mixture was ex-
tracted with CHCl3 (3 × 20 mL) The combined organic layers were
dried (MgSO4) and concentrated. The product was purified by flash
column chromatography (hexane–EtOAc) to give 15a (57.8 mg,
76%) as a colorless oil.
77 (13).
HRMS: m/z calcd for C33H40O3 (M+): 484.2978; found: 484.2985.
1-Ethyl-3,3-bis(3-phenylpropoxymethyl)cyclobutanecarboxyl-
ic Acid Ethyl Ester (15e)
Colorless oil.
IR (neat): 2932, 2858, 1727 (C=O), 1456, 1249, 1176, 1114 cm–1.
1H NMR: d = 0.78 (3 H, t, J = 7.4 Hz), 1.25 (3 H, t, J = 7.1 Hz),
1.78–1.94 (8 H, m), 2.28–2.32 (2 H, m), 2.64–2.72 (4 H, m), 3.35–
3.46 (8 H, m), 4.14 (2 H, q, J = 7.1 Hz), 7.17–7.30 (10 H, m).
IR (neat): 2953, 2924, 2854, 1604, 1496, 1455, 1367, 1113 cm–1.
MS: m/z (%) = 452 (M+, 28), 407 (8), 242 (12), 118 (100), 91 (68).
HRMS: m/z calcd for C29H40O4 (M+): 452.2927; found: 452.2923.
1H NMR: d = 0.79 (3 H, t, J = 7.4 Hz), 1.40 (2 H, quint, J = 7.4 Hz),
1.46–1.53 (2 H, m), 1.83–1.95 (6 H, m), 2.03–2.19 (1 H, m), 2.66–
2.71 (4 H, m), 3.25 (2 H, s), 3.38–3.58 (6 H, m), 7.15–7.29 (10 H,
m).
MS: m/z (%) = 380 (M+, 13), 244 (8), 118 (100), 91 (73).
HRMS: m/z calcd for C26H36O2 (M+): 380.2715; found: 380.2714.
1-Isopropyl-3,3-bis(3-phenylpropoxymethyl)cyclobutane (15f)
A solution of i-PrMgCl (2.0 M solution in THF, 0.38 mL, 0.75
mmol) was added to a solution of 1a (52.5 mg, 0.1 mmol) in THF
(1 mL) at –90 °C with stirring under argon atmosphere. The reac-
tion mixture was stirred and slowly allowed to warm to 0 °C. The
reaction was quenched by adding sat. aq NH4Cl (20 mL) and the
mixture was extracted with CHCl3 (3 × 20 mL). The combined or-
ganic layers were dried (MgSO4) and concentrated. The product
was purified by flash column chromatography (hexane–EtOAc) to
give 15f (28.5 mg, 72%) as a colorless oil.
1-Ethyl-1-methyl-3,3-bis(3-phenylpropoxymethyl)cyclobutane
(15b); Typical Procedure
A solution of EtMgCl (2.0 M solution in THF, 0.5 mL, 1.0 mmol)
was added to a solution of 1a (105 mg, 0.2 mmol) in THF (2 mL) at
–78 °C with stirring under argon atmosphere. The reaction mixture
was stirred and slowly allowed to warm to 0 °C. To the mixture
were added successively CuI (4 mg, 0.02 mmol) and MeI (0.06 mL,
1 mmol) and the mixture was stirred at 0 °C for 1 h. The reaction
was quenched by adding sat. aq NH4Cl (50 mL) and the mixture was
extracted with CHCl3 (3 × 20 mL). The combined organic layers
were dried (MgSO4) and concentrated. The product was purified by
flash column chromatography (hexane–EtOAc) to give 15b (54.5
mg, 69%) as a colorless oil.
IR (neat): 2951, 2857, 1603, 1496, 1454, 1364, 1112 cm–1.
1H NMR: d = 0.79 (6 H, d, J = 6.6 Hz), 1.37–1.50 (1 H, m), 1.50–
1.60 (2 H, m), 1.77–1.95 (7 H, m), 2.62–2.74 (4 H, m), 3.29 (2 H,
s), 3.38–3.51 (6 H, m), 7.14–7.30 (10 H, m).
MS: m/z (%) = 394 (M+, 12), 258 (8), 118 (100), 91 (70).
HRMS: m/z calcd for C27H38O2 (M+): 394.2872; found: 394.2869.
IR (neat): 2952, 2924, 2855, 1497, 1455, 1365, 1113 cm–1.
1-Isopropyl-1-methyl-3,3-bis(3-phenylpropoxymethyl)cyclobu-
tane (15g); Typical Procedure
1H NMR: d = 0.76–0.81 (3 H, m), 1.08 (3 H, s), 1.44 (2 H, q, J = 7.4
Hz), 1.46–1.53 (2 H, m), 1.57–1.70 (2 H, m), 1.83–1.93 (4 H, m),
2.65–2.72 (4 H, m), 3.36–3.48 (8 H, m), 7.15–7.29 (10 H, m).
MS: m/z (%) = 394 (M+, 13), 258 (8), 118 (100), 91 (76).
HRMS: m/z calcd for C27H38O2 (M+): 394.2871; found: 394.2871.
A solution of i-PrMgCl (2.0 M solution in THF, 0.38 mL, 0.75
mmol) was added to a solution of 1a (52.5 mg, 0.1 mmol) in THF
(1 mL) at –90 °C with stirring under argon atmosphere. The reac-
tion mixture was stirred and slowly allowed to warm to 0 °C. To the
mixture were successively added CuI (2 mg, 0.01 mmol) and MeI
(0.06 mL, 1 mmol) and the mixture was stirred at 0 °C for 1 h. The
reaction was quenched by adding sat. aq NH4Cl (20 mL) and the
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Multi-Substituted Cyclobutanes and Alkylidenecyclobutanes
405
mixture was extracted with CHCl3 (3 × 20 mL). The combined or-
ganic layers were dried (MgSO4) and concentrated. The product
was purified by flash column chromatography (hexane–EtOAc) to
give 15g (31.1 mg, 74%) as a colorless oil.
IR (neat): 2947, 2861, 1638, 1603, 1496, 1454, 1366, 1113, 911
cm–1.
1H NMR: d = 1.09–1.28 (2 H, m), 1.43–1.80 (9 H, m), 1.80–1.99 (6
H, m), 2.28–2.38 (2 H, m), 2.62–2.74 (4 H, m), 3.35–3.51 (8 H, m),
4.92–5.11 (2 H, m), 5.71–5.91 (1 H, m), 7.10–7.32 (10 H, m).
IR (neat): 2954, 2861, 1496, 1454, 1363, 1112 cm–1.
1H NMR: d = 0.71–0.84 (7 H, m), 0.97 (2 H, s), 1.49–1.78 (5 H, m),
1.81–1.95 (4 H, m), 2.64–2.74 (4 H, m), 3.29 (1 H, s), 3.34 (1 H, s),
3.37–3.52 (6 H, m), 7.12–7.34 (10 H, m).
MS: m/z (%) = 460 (M+, 18), 282 (19), 147 (22), 118 (89), 91 (100).
HRMS: m/z calcd for C32H44O2 (M+): 460.3341; found: 460.3343.
MS: m/z (%) = 408 (M+, 9), 118 (100), 91 (86).
HRMS: m/z calcd for C28H40O2 (M+): 408.3028; found: 408.3028.
[1-Cyclopentyl-3,3-bis(3-phenylpropoxymethyl)cyclobu-
tyl]phenylmethanone (15m)
Colorless oil.
1-Allyl-1-isopropyl-3,3-bis(3-phenylpropoxymethyl)cyclobu-
tane (15h)
IR (neat): 2946, 2863, 1722, 1674 (C=O), 1597, 1496, 1454, 1263,
1176, 1115, 910 cm–1.
Colorless oil.
1H NMR: d = 1.28–1.69 (8 H, m), 1.70–1.81 (2 H, m), 1.83–1.97 (2
H, m), 2.20–2.32 (2 H, m), 2.42–2.62 (5 H, m), 2.66–2.75 (2 H, m),
3.23 (2 H, s), 3.31 (2 H, t, J = 6.3 Hz), 3.38–3.50 (4 H, m), 7.05–
7.33 (10 H, m), 7.37–7.46 (2 H, m), 7.46–7.54 (1 H, m), 7.87–7.97
(2 H, m).
MS: m/z (%) = 524 (M+, 15), 147 (28), 118 (52), 105 (43), 91 (100).
HRMS: m/z calcd for C36H44O3 (M+): 524.3290; found: 524.3285.
IR (neat): 2953, 2930, 2858, 1638, 1603, 1496, 1454, 1365, 1113,
911 cm–1.
1H NMR: d = 0.78–0.87 (6 H, m), 1.48–1.96 (9 H, m), 2.15–2.54 (2
H, m), 2.64–2.74 (4 H, m), 3.27–3.48 (8 H, m), 4.91–5.09 (2 H, m),
5.71–5.96 (1 H, m), 7.11–7.32 (10 H, m).
MS: m/z (%) = 434 (M+, 8), 256 (11), 118 (73), 91 (100), 28 (23).
HRMS: m/z calcd for C30H42O2 (M+): 434.3185; found: 434.3186.
Acetylene 16a and Allene 16b; Typical Procedure
To a solution of phenylacetylene (0.035 mL, 0.3 mmol) in anhyd
THF (1 mL) in a flame-dried flask at 0 °C under argon atmosphere
were added successively n-BuLi (0.19 mL, 0.31 mmol) and HMPA
(0.05 mL, 0.3 mmol) to give a clear yellow solution. The mixture
was cooled to –90 °C and to this mixture was added a solution of 2a
(56 mg, 0.1 mmol) in THF (1 mL) followed by EtMgCl (2.0 M so-
lution in THF, 0.13 mL, 0.25 mmol) with stirring. The temperature
of the reaction mixture was gradually allowed to warm to –40 °C
and the stirring was continued at this temperature for 1 h. The tem-
perature of the mixture was then slowly allowed to warm to 0 °C.
The reaction was quenched by the addition of sat. aq NH4Cl (20
mL). The mixture was extracted with CHCl3 (3 × 20 mL) and the
combined organic layers were dried (MgSO4). The product was pu-
rified by silica gel column chromatography (hexane–EtOAc) to af-
ford an inseparable 3:10 mixture of 16a and 16b (34.1 mg, 78%) as
a colorless oil.
[1-Isopropyl-3,3-bis(3-phenylpropoxymethyl)cyclobutyl]phe-
nylmethanone (15i)
Colorless oil.
IR (neat): 2938, 2859, 1721, 1674 (C=O), 1598, 1496, 1453, 1263,
1114, 918 cm–1.
1H NMR: d = 0.92 (6 H, d, J = 6.6 Hz), 1.70–1.82 (2 H, m), 1.84–
1.97 (2 H, m), 2.22–2.39 (3 H, m), 2.45–2.62 (4 H, m), 2.65–2.75 (2
H, m), 3.25 (2 H, s), 3.32 (2 H, t, J = 6.3 Hz), 3.37–3.50 (4 H, m),
7.07–7.33 (10 H, m), 7.37–7.46 (2 H, m), 7.46–7.56 (1 H, m), 7.84–
7.94 (2 H, m).
MS: m/z (%) = 498 (M+, 10), 319 (10), 118 (70), 105 (48), 91 (100).
HRMS: m/z calcd for C34H42O3 (M+): 498.3134; found: 498.3135.
1-Cyclopentyl-3,3-bis(3-phenylpropoxymethyl)cyclobutane
(15j)
Colorless oil.
IR (neat): 2945, 2858, 1496, 1453, 1113 cm–1.
1H NMR: d = 1.02–1.12 (2 H, m), 1.44–1.60 (6 H, m), 1.60–1.70 (2
H, m), 1.77–1.94 (7 H, m), 1.99–2.10 (1 H, m), 2.64–2.72 (4 H, m),
3.31 (2 H, s), 3.39–3.48 (6 H, m), 7.12–7.30 (10 H, m).
IR (neat): 3026, 2930, 2858, 2343 (C≡C), 1950 (C=C=C), 1496,
1454, 1112, 746, 699 cm–1.
1H NMR: d = 1.82–2.01 (4 H, m), 2.60–2.76 (4 H, m), 2.76–2.84 (4
H, m), 2.84–2.90 (0.23 H, m), 3.32–3.60 (8 H, m), 6.15 (0.77 H, m,
C=C=CH), 7.10–7.35 (15 H, m).
MS: m/z (%) = 452 (M+, trace), 167 (13), 128 (14), 118 (100), 91
(87).
MS: m/z (%) = 420 (M+, 12), 284 (6), 118 (100), 91 (70).
HRMS: m/z calcd for C29H40O2 (M+): 420.3028; found: 420.3035.
HRMS: m/z calcd for C32H36O2 (M+): 452.2715; found: 452.2714.
1-Cyclopentyl-1-methyl-3,3-bis(3-phenylpropoxymethyl)cy-
clobutane (15k)
Colorless oil.
IR (neat): 2949, 2863, 1603, 1496, 1454, 1372, 1113 cm–1.
Acetylene 16c and Allene 16d
Colorless oil (an inseparable 9:10 mixture of 16c and 16d).
IR (neat): 3026, 2928, 2858, 2344 (C≡C), 1949 (C=C=C), 1601,
1508, 1224, 1113 cm–1.
1H NMR: d = 1.03–1.28 (5 H, m), 1.42–1.72 (8 H, m), 1.73–1.81 (2
H, m), 1.83–1.99 (5 H, m), 2.62–2.74 (4 H, m), 3.37 (2 H, s), 3.40–
3.51 (6 H, m), 7.08–7.32 (10 H, m).
1H NMR: d = 1.84–2.02 (4 H, m), 2.64–2.76 (4 H, m), 2.76–2.82 (4
H, m), 2.82–2.88 (0.47 H, m), 3.32–3.60 (8 H, m), 6.12 (0.53 H, m,
C=C=CH), 6.92–6.97 (2 H, m), 7.10–7.35 (12 H, m).
MS: m/z (%) = 434 (M+, 6), 298 (11), 118 (100), 91 (96).
MS: m/z (%) = 470 (M+, trace), 118 (100), 91 (73).
HRMS: m/z calcd for C30H42O2 (M+): 434.3185; found: 434.3180.
HRMS: m/z calcd for C32H35FO2 (M+): 470.2621; found: 470.2627.
1-Allyl-1-cyclopentyl-3,3-bis(3-phenylpropoxymethyl)cyclobu-
tane (15l)
Colorless oil.
2-[3,3-Bis(ethoxymethylcyclobutyl)]thiophene (16e); Typical
Procedure
A solution of EtMgCl (2.0 M solution in THF, 0.125 mL, 0.25
mmol) was added to a solution of 2b (34.5 mg, 0.1 mmol) in THF
(1 mL) at –90 °C with stirring under argon atmosphere. Thiophene
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T. Satoh et al.
PAPER
(0.04 mL, 0.5 mmol) was added to a solution of n-BuLi (1.65 M so-
lution in n-hexane, 0.3 mL, 0.5 mmol) in anhyd THF (1 mL) in an
another flame-dried flask at –90 °C under argon atmosphere to give
a clear yellow solution. This solution was added to the solution of
the carbenoid via a cannula. The reaction mixture was stirred and
slowly allowed to warm to 0 °C and the reaction was quenched with
sat. aq NH4Cl (20 mL). The mixture was extracted with CHCl3 (3 ×
20 mL) and the combined organic layers were dried (MgSO4). The
product was purified by silica gel column chromatography (hex-
ane–EtOAc) to afford 16e (8.6 mg, 34%) as a colorless oil.
N-Cyclobutyl-N-methyl-p-anisidine (19c)
Light yellow oil.
IR (neat): 2938, 2857, 1727, 1511, 1242, 1040, 819 cm–1.
1H NMR: d = 1.64–1.73 (2 H, m), 1.95–2.09 (2 H, m), 2.14–2.24 (2
H, m), 2.71 (3 H, s), 3.66–3.76 (1 H, m), 3.76 (3 H, s), 6.82 (4 H, s).
MS: m/z (%) = 191 (M+, 22), 163 (100), 148 (18), 122 (32).
HRMS: m/z calcd for C12H17NO (M+): 191.1310; found: 191.1308.
4-Chloro-N-cyclobutyl-N-methylaniline (19d)
Light brown oil.
IR (neat): 2974, 2931, 2859, 1731, 1444, 1376, 1354, 1111, 825
cm–1.
1H NMR: d = 1.15–1.27 (6 H, m), 2.04–2.16 (2 H, m), 2.28–2.39 (2
H, m), 3.38 (2 H, s), 3.44–3.60 (6 H, m), 3.69 (1 H, quint, J = 8.9
Hz), 6.79–6.85 (1 H, m), 6.92 (1 H, dd, J = 5.1, 3.4 Hz), 7.11 (1 H,
dd, J = 5.1, 1.1 Hz).
MS: m/z (%) = 254 (M+, 5), 110 (100).
HRMS: m/z calcd for C14H22O2S (M+): 254.1341; found: 254.1345.
IR (neat): 2941, 2871, 1598, 1498, 1327, 1248, 1137, 1099, 811
cm–1.
1H NMR: d = 1.65–1.75 (2 H, m), 2.00–2.14 (2 H, m), 2.19–2.29 (2
H, m), 2.80 (3 H, s), 3.85–3.96 (1 H, m), 6.67–6.70 (2 H, m), 7.13–
7.17 (2 H, m).
MS: m/z (%) = 195 (M+, 27), 167 (100), 138 (11), 131 (21), 125
(23), 111 (17).
HRMS: m/z calcd for C11H14ClN (M+): 195.0815; found: 195.0823.
2-[3,3-Bis(ethoxymethylcyclobutyl)]-5-methylthiophene (16f)
Colorless oil.
N-Cyclobutyl-N-methyl-1-naphthylamine (19e)
Light orange oil.
IR (neat): 2974, 2931, 2862, 1445, 1376, 1354, 1170, 1110, 881
cm–1.
1H NMR: d = 1.14–1.28 (6 H, m), 1.98–2.12 (2 H, m), 2.24–2.36 (2
H, m), 2.43 (3 H, s), 3.37 (2 H, s), 3.44–3.68 (7 H, m), 6.51–6.62 (2
H, m).
MS: m/z (%) = 268 (M+, 5), 124 (100).
HRMS: m/z calcd for C15H24O2S (M+): 268.1497; found: 268.1498.
IR (neat): 3047, 2936, 2852, 1576, 1466, 1395, 1343, 1294, 1078,
1056, 801, 775 cm–1.
1H NMR: d = 1.65–1.74 (2 H, m), 1.91–2.05 (2 H, m), 2.12–2.22 (2
H, m), 2.73 (3 H, s), 3.78–3.89 (1 H, m), 6.94–6.97 (1 H, m), 7.33–
7.38 (1 H, m), 7.43–7.53 (3 H, m), 7.78–7.82 (1 H, m), 8.26–8.29 (1
H, m).
MS: m/z (%) = 211 (M+, 19), 183 (100), 168 (13), 142 (54), 127
(18), 90 (10).
N-Cyclobutyl-N-methylaniline (19a)
To a solution of N-methylaniline (0.066 mL, 0.6 mmol) in anhyd
THF (2 mL) in a flame-dried flask at 0 °C under argon atmosphere
was added n-BuLi (1.57 M solution in hexane, 0.38 mL, 0.6 mmol)
dropwise with stirring. The reaction mixture was cooled to –78 °C
and HMPA (0.1 mL, 0.6 mmol) and a solution of 2c (45.7 mg, 0.2
mmol) in anhyd THF (2 mL) were added dropwise with stirring. Af-
ter 5 min, EtMgCl (2.0 M solution in THF, 0.25 mL, 0.5 mmol) was
added to the mixture and the temperature of the mixture was slowly
allowed to warm to –20 °C. The reaction was quenched by the ad-
dition of sat. aq NH4Cl (20 mL) and the mixture was extracted with
CHCl3 (3 × 20 mL) and the combined organic layers were dried
(MgSO4). The product was purified by silica gel column chroma-
tography (hexane–EtOAc) to afford 19a (11.2 mg, 35%) as a light
yellow oil.
HRMS: m/z calcd for C15H17N (M+): 211.1361; found: 211.1356.
10-[3,3-Bis(3-phenylpropoxymethyl)cyclobutyl]-10H-phenothi-
azine (20)
Light orange oil.
IR (neat): 2934, 2858, 1593, 1571, 1496, 1459, 1320, 1287, 1258,
1236, 1217, 1111, 754 cm–1.
1H NMR: d = 1.75–1.84 (2 H, m), 1.85–1.92 (2 H, m), 1.93–2.01 (2
H, m), 2.56–2.63 (4 H, m), 2.73–2.78 (2 H, m), 3.30–3.35 (4 H, m),
3.50–3.57 (4 H, m), 4.48 (1 H, quint, J = 7.0 Hz), 6.56–6.61 (2 H,
m), 6.90–6.95 (2 H, m), 7.07–7.32 (14 H, m).
MS: m/z (%) = 549 (M+, 30), 225 (100), 198 (15), 91 (19).
HRMS: m/z calcd for C36H39NO2S (M+): 549.2702; found:
IR (neat): 2972, 2940, 1599, 1504, 1321 cm–1.
549.2700.
1H NMR: d = 1.65–1.75 (2 H, m), 2.02–2.15 (2 H, m), 2.20–2.30 (2
H, m), 2.83 (3 H, s), 3.90–4.01 (1 H, m), 6.73–6.81 (3 H, m), 7.20–
7.25 (2 H, m).
MS: m/z (%) = 161 (M+, 16), 132 (100), 117 (13), 91 (23), 77 (18).
HRMS: m/z calcd for C11H15N (M+): 161.1204; found: 161.1202.
3,3-Bis(3-phenylpropoxymethyl)-1-benzylidenecyclobutane
(6a); Typical Procedure
A solution of EtMgCl (2.0 M solution in THF, 0.25 mL, 0.5 mmol)
was added to a solution of 1a (105 mg, 0.2 mmol) in THF (2 mL) at
–78 °C with stirring under argon atmosphere. In an another flame-
dried flask, a solution of benzyl phenyl sulfone (139 mg, 0.6 mmol)
in THF (0.5 mL) was added to a solution of n-BuLi (1.57 M solution
in n-hexane, 0.38 mL, 0.6 mmol) in anhyd THF (2 mL) at 0 °C un-
der argon atmosphere to give a clear yellow solution. This solution
was cooled to –78 °C and was added to the solution of the cyclobu-
tylmagnesium carbenoid via a cannula. The reaction mixture was
stirred and slowly allowed to warm to –20 °C; then the reaction was
quenched with sat. aq NH4Cl (20 mL). The mixture was extracted
with CHCl3 (3 × 20 mL) and the solution was dried (MgSO4). The
product was purified by silica gel column chromatography (hex-
ane–EtOAc) to afford 6a (73.1 mg, 83%) as a colorless oil.
N-Cyclobutyl-N-methyl-p-toluidine (19b)
Light yellow oil.
IR (neat): 2929, 2859, 1618, 1518, 1316, 806 cm–1.
1H NMR: d = 1.74–1.95 (2 H, m), 1.99–2.12 (2 H, m), 2.17–2.26 (2
H, m), 2.25 (3 H, s), 2.77 (3 H, s), 3.80–3.90 (1 H, m), 6.72–6.75 (2
H, m), 7.02–7.05 (2 H, m).
MS: m/z (%) = 175 (M+, 21), 147 (93), 146 (100), 132 (16), 106
(26), 91 (24).
HRMS: m/z calcd for C12H17N (M+): 175.1361; found: 175.1360.
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IR (neat): 3026, 2942, 2858, 1680, 1601, 1496, 1454, 1112, 910,
742 cm–1.
IR (neat): 3026, 2943, 2858, 1678, 1603, 1497, 1455, 1367, 1114,
876, 745, 699 cm–1.
1H NMR: d = 1.84–1.94 (4 H, m), 2.66–2.71 (6 H, m), 2.85 (2 H, s),
3.46 (4 H, t, J = 6.3 Hz), 3.48 (4 H, s), 6.19 (1 H, m), 7.13–7.21 (7
H, m), 7.24–7.32 (8 H, m).
1H NMR: d = 1.84–1.93 (4 H, m), 2.50 (4 H, t, J = 2.4 Hz), 2.65–
2.70 (4 H, m), 3.44 (4 H, s), 3.45 (4 H, t, J = 6.3 Hz), 4.81–4.84 (2
H, m), 7.15–7.19 (6 H, m), 7.25–7.29 (4 H, m).
MS: m/z (%) = 440 (M+, 7), 305 (11), 304 (50), 170 (27), 168 (30),
MS: m/z (%) = 364 (M+, trace), 228 (5), 119 (25), 118 (61), 91
156 (19), 155 (100), 142 (8), 129 (12), 119 (18), 91 (93).
(100).
HRMS: m/z calcd for C31H36O2 (M+): 440.2715; found: 440.2708.
HRMS: m/z calcd for C25H32O2 (M+): 364.2402; found: 364.2395.
3,3-Bis(3-phenylpropoxymethyl)-1-(1-naphthyl)methylidenecy-
clobutane (6b)
3,3-Bis(3-phenylpropoxymethyl)-1-ethylidenecyclobutane (6g)
Colorless oil.
Colorless oil.
IR (neat): 3027, 2929, 2856, 1603, 1497, 1455, 1367, 1114, 745
cm–1.
1H NMR: d = 1.49–1.52 (3 H, m), 1.84–1.93 (4 H, m), 2.41–2.42 (4
H, m), 2.65–2.70 (4 H, m), 3.44 (4 H, s), 3.45 (4 H, t, J = 6.3 Hz),
5.17–5.25 (1 H, m), 7.15–7.19 (6 H, m), 7.25–7.29 (4 H, m).
MS: m/z (%) = 378 (M+, trace), 242 (10), 119 (25), 118 (47), 108
(13), 91 (100).
IR (neat): 3026, 2942, 2858, 1691, 1603, 1496, 1454, 1113, 909,
782, 733 cm–1.
1H NMR: d = 1.86–1.92 (4 H, m), 2.66–2.70 (4 H, m), 2.78 (4 H, s),
3.46 (4 H, t, J = 6.3 Hz), 3.50 (4 H, s), 6.90–6.92 (1 H, m), 7.15–
7.25 (10 H, m), 7.39–7.50 (4 H, m), 7.69–7.71 (1 H, m), 7.82–7.84
(1 H, m), 8.10–8.12 (1 H, m).
MS: m/z (%) = 490 (M+, 46), 354 (30), 218 (23), 206 (20), 205
(100), 203 (10), 179 (17), 165 (25), 119 (8), 91 (51).
HRMS: m/z calcd for C26H34O2 (M+): 378.2559; found: 378.2557.
HRMS: m/z calcd for C35H38O2 (M+): 490.2872; found: 490.2866.
3,3-Bis(3-phenylpropoxymethyl)-1-isopropylidenecyclobutane
(6h)
Colorless oil.
3,3-Bis(3-phenylpropoxymethyl)-1-(1-phenyl)ethylidenecyclo-
butane (6c)
Colorless oil.
IR (neat): 3027, 2925, 2856, 1603, 1497, 1455, 1370, 1112, 745
cm–1.
1H NMR: d = 1.49–1.53 (6 H, m), 1.84–1.93 (4 H, m), 2.37–2.38 (4
H, m), 2.65–2.70 (4 H, m), 3.43 (4 H, s), 3.45 (4 H, t, J = 6.3 Hz),
7.15–7.19 (6 H, m), 7.24–7.29 (4 H, m).
IR (neat): 3026, 2933, 2858, 1600, 1496, 1454, 1114, 910, 760 cm–1.
1H NMR: d = 1.84–1.93 (7 H, m), 2.62–2.71 (8 H, m), 3.45 (4 H, t,
J = 6.3 Hz), 3.46 (4 H, s), 7.14–7.18 (7 H, m), 7.23–7.31 (8 H, m).
MS: m/z (%) = 454 (M+, 7), 318 (31), 200 (3), 182 (16), 169 (100),
MS: m/z (%) = 392 (M+, trace), 256 (28), 118 (24), 107 (82), 91
129 (10), 118 (14), 91 (58).
(100).
HRMS: m/z calcd for C32H38O2 (M+): 454.2872; found: 454.2879.
HRMS: m/z calcd for C27H36O2 (M+): 392.2715; found: 392.2718.
3,3-Bis(3-phenylpropoxymethyl)-1-(ethen-1-yl)methylidenecy-
clobutane (6d)
Benzylidenecyclobutane (6i)
Colorless oil.
Colorless oil.
IR (neat): 3024, 2980, 2953, 2911, 1676, 1597, 1498, 1448, 909,
860, 764 cm–1.
1H NMR: d = 2.04–2.16 (2 H, m), 2.85–2.91 (2 H, m), 3.01–3.09 (2
H, m), 6.06–6.09 (1 H, m), 7.11–7.31 (5 H, m).
MS: m/z (%) = 144 (M+, 49), 139 (10), 129 (100), 128 (26), 116
(39), 115 (72).
HRMS: m/z calcd for C11H12 (M+): 144.0939; found: 144.0946.
IR (neat): 3026, 2928, 2856, 1676, 1605, 1496, 1454, 1114, 992,
898, 745 cm–1.
1H NMR: d = 1.83–1.92 (4 H, m), 2.53 (2 H, s), 2.58 (2 H, s), 2.62–
2.70 (4 H, m), 3.44 (4 H, s), 3.45 (4 H, t, J = 6.3 Hz), 4.91–4.95 (1
H, m), 5.00–5.06 (1 H, m), 5.87–5.90 (1 H, m), 6.21–6.34 (1 H, m),
7.14–7.19 (6 H, m), 7.24–7.29 (4 H, m).
MS: m/z (%) = 390 (M+, trace), 254 (10), 120 (16), 119 (21), 118
(21), 105 (20), 92 (23), 91 (100). HRMS: m/z calcd for C27H34O2
(M+): 390.2559; found: 390.2560.
1-Naphthyl-1-methylidenecyclobutane (6j)
Colorless oil.
IR (neat): 3046, 2951, 2913, 1671, 1590, 1508, 1395, 1015, 796,
778 cm–1.
3,3-Bis(3-phenylpropoxymethyl)-1-(2-methylethyn-1-yl)meth-
ylidenecyclobutane (6e)
1H NMR: d = 2.05–2.15 (2 H, m), 2.93–2.99 (4 H, m), 6.77–6.78 (1
H, m), 7.34–7.51 (4 H, m), 7.67–7.70 (1 H, m), 7.80–7.84 (1 H, m),
8.08–8.11 (1 H, m).
MS: m/z (%) = 194 (M+, 67), 179 (71), 165 (100).
HRMS: m/z calcd for C15H14 (M+): 194.1096; found: 194.1097.
Colorless oil.
IR (neat): 3026, 2915, 2856, 2219 (C≡C), 1666, 1603, 1496, 1455,
1368, 1112, 924, 868, 746 cm–1.
1H NMR: d = 1.83–1.92 (4 H, m), 1.95–1.96 (3 H, m), 2.54 (2 H, s),
2.60 (2 H, s), 2.65–2.70 (4 H, m), 3.43 (4 H, s), 3.44 (4 H, t, J = 6.3
Hz), 5.28–5.30 (1 H, m), 7.15–7.20 (6 H, m), 7.25–7.30 (4 H, m).
MS: m/z (%) = 402 (M+, trace), 266 (28), 132 (67), 118 (30), 117
(78), 91 (100).
HRMS: m/z calcd for C28H34O2 (M+): 402.2559; found: 402.2554.
1-Phenyl-1-ethylidenecyclobutane (6k)
Colorless oil.
IR (neat): 2977, 2927, 1599, 1496, 1443, 1375, 1054, 1026 cm–1.
1H NMR: d = 1.89 (3 H, s), 1.93–2.04 (2 H, m), 2.81–2.92 (4 H, m),
7.13–7.20 (1 H, m), 7.28–7.33 (4 H, m).
MS: m/z (%) = 158 (M+, 55), 143 (100), 129 (64), 115 (48).
HRMS: m/z calcd for C12H14 (M+): 158.1096; found: 158.1093.
3,3-Bis(3-phenylpropoxymethyl)-1-methylidenecyclobutane
(6f)
Colorless oil.
Synthesis 2011, No. 3, 397–408 © Thieme Stuttgart · New York

408
T. Satoh et al.
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Acknowledgment
We gratefully acknowledge the support by a Grant-in-Aid for
Scientific Research No. 19590018 and 22590021 from the Ministry
of Education, Culture, Sports, Science and Technology, Japan, and
TUS Grant for Research Promotion from Tokyo University of
Science.
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Synthesis 2011, No. 3, 397–408 © Thieme Stuttgart · New York