Reactions of methylenecyclobutanes with silver acetate and iodine

Article abstract of DOI:10.1016/j.tet.2007.07.046

Methylenecyclobutanes undergo an interesting rearrangement reaction in the presence of silver acetate and iodine at room temperature (20 °C) in dichloromethane to give the corresponding aryl-(1-arylcyclobutyl)methanones in good to high yields within short

Full text of DOI:10.1016/j.tet.2007.07.046

Tetrahedron 63 (2007) 9599–9604
Reactions of methylenecyclobutanes with silver acetate and iodine
*
Min Jiang, Le-Ping Liu and Min Shi
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
Received 7 June 2007; revised 14 July 2007; accepted 16 July 2007
Available online 20 July 2007
Abstract—Methylenecyclobutanes undergo an interesting rearrangement reaction in the presence of silver acetate and iodine at room
temperature (20 ꢀC) in dichloromethane to give the corresponding aryl-(1-arylcyclobutyl)methanones in good to high yields within short
reaction time. A plausible reaction mechanism has been discussed on the basis of control and O18-labeling experiments.
Ó 2007 Elsevier Ltd. All rights reserved.
Ph
Ph
Ph
Ph
1. Introduction
peracetic acid or ozone
O
Oxidation of alkenes using iodine and silver acetate has long
been known to give the corresponding dihydroxy prod-
ucts.1,2 Previously, we reported that using methylenecyclo-
propanes (MCPs), a kind of highly strained but readily
accessible alkenes, as substrates, the ring-opening reaction
takes place to produce the corresponding 2,4-diiodo-buta-
1-enes in good yields in the presence of iodine or in the
coexistence of silver acetate under mild conditions (Scheme
1).3,4 On the other hand, it has been well known that methyl-
enecyclobutanes (MCBs),5 a class of moderately strained
alkenes, could be oxidized by peracetic acid or ozone as
well as thallium(III) oxide to give the corresponding cyclo-
pentanone derivatives in good yields through a rearrange-
ment (Scheme 2).6 On the basis of the above results, we
attempted to examine the reaction of MCBs in the presence
of iodine (I2) and silver acetate to understand their reaction
pathway. In this paper, we wish to report that methylene-
cyclobutanes (MCBs) can undergo an interesting rearrange-
ment reaction in the presence of iodine and silver acetate
at room temperature (20 ꢀC) in dichloromethane to give
the corresponding cyclobutylmethanone derivatives in
good to high yields within short reaction time rather than
cyclopentanone derivatives.
Scheme 2. Oxidation of methylenecyclobutanes to form cyclopentanone.
2. Results and discussion
At first, we investigated the rearrangement reaction of diphe-
nylmethylenecyclobutane 1a in the presence of silver acetate
and iodine to develop the optimal conditions. The results are
summarized in Table 1. Using 1a (1.0 equiv) with I2
(1.2 equiv) and AgOAc (2.4 equiv) in dichloromethane at
room temperature (20 ꢀC), 2a was produced in 61% yield
along with trace of cyclopentanone after 2 h under ambient
atmosphere (Table 1, entry 1). When the ratio of 1a/I2/
AgOAc increased to 1/1.5/3, the color of iodine immediately
disappeared within 10 min and the yield of 2a could be
achieved in 87% (Table 1, entry 2). When AgCO3 or
AgNO3 was used to replace AgOAc, the yield of 2a de-
creased to 41% and 68%, respectively, under the similar con-
ditions (Table 1, entries 3 and 4). In the presence of I2 and
Ag2O, no reaction occurred (Table 1, entry 5). Using bro-
mine to replace iodine, only 22% of 2a was produced under
identical conditions (Table 1, entry 6). When the reaction
was carried out at 0 ꢀC, 2a was obtained in 75% yield under
the standard conditions (Table 1, entry 7). Further examina-
tion of the solvent effects revealed that dichloromethane is
the best one for this transformation (Table 1, entries 8–12).
Ph
Ph
Ph
Ph
I
CH2Cl2
I2
+
I
Scheme 1. Ring-opening reaction of methylenecyclopropanes.
Under these optimal reaction conditions, we next carried out
this interesting rearrangement reaction of a variety of meth-
ylenecyclobutanes 1 with silver acetate and iodine. The
results are summarized in Table 2. We found that the corre-
sponding aryl-(1-arylcyclobutyl)methanone products 2 were
Keywords: Methylenecyclobutanes; Rearrangement; Iodine; Silver acetate.
* Corresponding author. Tel.: +86 21 54925137; fax: +86 21 64166128;
e-mail: mshi@mail.sioc.ac.cn
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.07.046

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M. Jiang et al. / Tetrahedron 63 (2007) 9599–9604
Table 1. Optimized reaction conditions of 1a with X in the presence of I2
2l were obtained as single products through the phenyl mi-
gration (Table 2, entries 8–11). The possible reason is that
the aromatic group can much more easily migrate than alkyl
group, which exclusively results in the formation of alkyl
ketone. For MCB 1h (R1¼H, R2¼p-MeC6H4), complicated
reaction products were formed without the formation of the
expected product 2h (Table 2, entry 7).
O
C6H5
solvent
C6H5
H2O
+
I2
+
AgX
C6H5
1a
C6H5
2a
Entrya Solvent AgX
1a/I2/AgX Temp (ꢀC) Time Yieldb (%)
2a
On the basis of computational calculation on 13C chemical
shifts by gauge including atomic orbital (GIAO) method at
B3LYP/6-31G* level using Gaussian03 program, we con-
firmed that electron-rich aromatic group migrates more
preferentially than electron-poor ones for unsymmetrical
MCBs 1f and 1g (Supplementary data).
1
2
3
CH2Cl2 AgOAc 1/1.2/2.4 rt
CH2Cl2 AgOAc 1/1.5/3 rt
CH2Cl2 Ag2CO3 1/1.5/1.5 rt
2 h 61
10 min 87
1 h
2 h
2 h
41
68
N.R.
4
5
6
7
CH2Cl2 AgNO3 1/1.5/3
CH2Cl2 Ag2O 1/1.5/3
CH2Cl2 AgOAc 1/1.5/3
CH2Cl2 AgOAc 1/1.5/3
rt
rt
rt
0
40 min 22c
10 min 75
8
9
10
11
12
THF
Et2O
AgOAc 1/1.5/3
AgOAc 1/1.5/3
rt
rt
rt
rt
rt
5 h
5 h
5 h
5 h
5 h
57
49
23
77
68
The structures of all these products reported in this paper
1
were determined by H and 13C NMR spectroscopic data,
and HRMS or microanalysis. The structure of 2b was unam-
CH3CN AgOAc 1/1.5/3
DCE AgOAc 1/1.5/3
Toluene AgOAc 1/1.5/3
biguously determined by X-ray diffraction (Fig. 1).7
N.R. ¼ no reaction.
a
Because these reactions were carried out under ambient
atmosphere and all of the solvents and reagents were used
without further drying, the ambient water may play a key
role in this rearrangement reaction and the oxygen atom
might be derived from the ambient water. Therefore, we
carefully studied the water effect on the reaction in anhy-
drous dichloromethane under argon atmosphere. The results
are summarized in Table 3. As can be seen from Table 3,
with the addition of water from 0.5 equiv to 1.0 equiv, the
yield of 2a was indeed improved from 62% to 87%, although
2.0 equiv, 4.0 equiv or 5.0 equiv of water did not make any
significant difference (Table 3, entries 2–5). In the absence
of water, 2a was obtained in 36% yield, suggesting that trace
of water is still involved in this reaction even using anhy-
drous reagents and solvent under argon atmosphere (Table
1, entry 1). The best result was obtained with the addition
of 1.0 equiv of water.
Reaction conditions: 1a (0.3 mmol), I2 (0.45 or 0.36 mmol), AgX
(0.9 mmol), solvent (2.0 mL), and the reactions were carried out at
room temperature or 0 ꢀC.
b
c
Isolated yields.
Br2 was used instead of I2.
obtained in moderate to good yields within 10 min for a
variety of MCBs 1 with electron-rich, electron-neutral, and
electron-poor substituents on the benzene ring under ambi-
ent atmosphere. The effect of the nature of the substituents
is not very significant. However, as can be seen from Table
2, in the presence of an electron-donating substituent at the
para-position of benzene ring leads to a higher yield. For un-
symmetrical MCBs 1f and 1g, the corresponding products 2f
and 2g were obtained as isomeric mixtures in which the ra-
tios were determined by GLC analysis (Table 2, entries 5 and
6) (Supplementary data). But for unsymmetrical MCBs 1i,
1j, 1k, and 1l, the corresponding products 2i, 2j, 2k, and
In order to clarify the reaction mechanism, H218O (18O con-
tent 97.7%) was used in the reaction of 1a with iodine and
silver acetate under the standard conditions. It was found
that the corresponding product 2a-18O was obtained in
82% yield along with 61% of 18O content, indicating that
Table 2. Reaction of 1 with I2 and AgOAc under the optimal conditions
O
R1
CH2Cl2
R2
I2
+ H2O
+ AgOAc
+
r.t., 10 min.
R1
R2
2
1 (R1, R2 = aromatic group)
(R1 = aromatic group, R2 = alkyl group)
Entrya
1 (R1/R2)
Yieldb (%)
2
1
2
3
4
5
6
7
8
1b (p-ClC6H4/p-ClC6H4)
1c (p-MeC6H4/p-MeC6H4)
1d (p-FC6H4/p-FC6H4)
1e (p-MeOC6H4/p-MeOC6H4)
1f (p-ClC6H4/C6H5)
1g (m,p-Me2C6H3/C6H5)
1h (p-MeC6H4/H)
1i (p-MeC6H4/Me)
2b, 60
2c, 73
2d, 63
2e, 77
2f, 72 (2:1)c
2g, 81 (3.2:1)c
2h, —d
2i, 43
9
10
11
1j (p-BrC6H4/Me)
1k (p-CF3C6H4/Me)
1l (p-MeC6H4/(CH2)4CH3)
2j, 73
2k, 36
2l, 41
a
Reactions were carried out at room temperature. Reaction conditions: 1
(0.4 mmol), I2 (0.6 mmol), AgOAc (1.2 mmol), and CH2Cl2 (3.0 mL).
Isolated yields.
Isomeric mixtures.
No expected product.
b
c
d
Figure 1. X-ray crystal structure of compound 2b.

M. Jiang et al. / Tetrahedron 63 (2007) 9599–9604
9601
Table 3. Studies on the influence of the amount of water on the reaction
using anhydrous reagents under argon atmosphere
substituent at the benzene ring more than an electron-
withdrawing one.12 However, when water attacks the posi-
tion b of intermediate A, intermediate D can be formed,
which produces the corresponding cyclopentanone 3a as
a by-product. In cationic intermediate A, the resonance-
stabilized cationic intermediate A-1 is more stable than the
resonance-stabilized cationic intermediate A-2 by two
aromatic groups and a cyclobutane moiety (Fig. 2).9a,13 Sub-
sequently, phenonium ion intermediate C from intermediate
A-1 can be more easily formed, which has been disclosed by
Kakis et al.14 Therefore, the attack of water on the position
a can exclusively take place to give the corresponding
rearranged product 2a as a major product.
O
C6H5
C6H5
CH2Cl2
H2O
C6H5
C6H5
I2
+
+ AgOAc
1a
2a
Entrya
H2O (equiv)
Time (min)
Yieldb (%)
2a
1
2
3
4
5
6
0
10
10
10
10
20
20
36
62
87
87
85
85
0.5
1.0
2.0
4.0
5.0
I
I
b
I
C6H5
a
C6H5
C6H5
a
a
Reaction conditions: 1a (0.3 mmol), I2 (0.45 mmol), AgOAc (0.9 mmol),
CH2Cl2 (2.0 mL), H2O (x equiv), and the reactions were carried out at
room temperature.
+
+
b
+
a
b
C6H5
C6H5
C6H5
A
A-1
A-2
b
Isolated yields.
Figure 2. Cationic intermediates.
the oxygen atom is indeed derived from water (Scheme 3).
The lower 18O content of 2a (61%) is due to that the ambient
moisture (H2O) takes part into the reaction as well.
In order to rule out the possibility of this rearrangement
through an epoxide intermediate, we prepared the corre-
sponding epoxide from 1a using m-CPBA in dichlorome-
thane, and found that the corresponding cyclopentanone 3a
was obtained in 76% yield in the presence of acetic acid,
indicating that 2a might be derived from the iodonium inter-
mediate A (Scheme 5). In fact, Takada has already reported
that cyclopentanone derivatives can be obtained via the ring
enlargement of the corresponding epoxides derived from
alkylidenecyclobutanes in the presence of Lewis acid such
as BF3$OEt2.15
18O
C6H5
CH2Cl2
C6H5
C6H5
2a-18O 82% (18O content: 61%)
+
I2
+ AgOAc
H218O
C6H5
1a
Scheme 3. Isotopic labeling experiment using H218O under the reaction
conditions.
A plausible reaction mechanism for this rearrangement
reaction of methylenecyclobutanes is shown in Scheme 4.
Initially, the reaction of 1a with iodine and silver acetate
generates iodonium intermediate A.8,9 Then, cationic inter-
mediate B is formed when water attacks the position a of
intermediate A, which produces the corresponding rear-
ranged product 2a (path a) through the phenonium ion
C.10–12 As shown in Table 2, the relatively higher yields of
2 with an electron-donating substituent at the para-position
of benzene ring can partially prove the existence of interme-
diate C, because it can be stabilized by an electron-donating
O
C6H5
C6H5
C6H5
C6H5
O
HOAc (1.5 equiv.)
8 h
m-CPBA (1.5 equiv.)
1a
CH2Cl2, 0 - 15 °C, 1.5 h
3a, 76%
Scheme 5. Rearrangement through the corresponding epoxide.
We also examined the reaction of alkene 4 with iodine and
silver acetate in the presence of water under identical condi-
tions. The corresponding product 5 was only isolated in 34%
yield along with 51% of the starting material 4 was recov-
ered after 2 h, suggesting that cyclobutane moiety is required
in this interesting rearrangement reaction (Scheme 6).
AgOAc
I
C6H5
a
C6H5
O
2a
a
C6H5
O
H
C6H5
path a
I
O
H
B
CH2Cl2
C6H5
C6H5
5, 34%
AgI
I2
+
+ AgOAc
H2O, 2 h
C6H5
C
4
I2 + AgOAc
C6H5
+
1a
a
b
A
Scheme 6. Reaction of alkene 4 with iodine and silver acetate.
C6H5
AgI
AgOAc
C6H5
H2O
path b
O
I
C6H5
C6H5
3. Conclusion
b
C6H5
O
AgI + HOAc
3a
In summary, we have disclosed an interesting rearrangement
reaction of MCBs with silver acetate and iodine at room
temperature in dichloromethane to give the corresponding
rearranged products in moderate to good yields under mild
H
D
Scheme 4. Proposed mechanism for the reaction of 1a with iodine and silver
acetate.

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M. Jiang et al. / Tetrahedron 63 (2007) 9599–9604
1
conditions.14 The corresponding ketones 2 may be useful
intermediates in organic synthesis. Efforts are in progress
to elucidate the mechanistic details of this reaction and to
determine its scope and limitations.
1607, 1572, 1512, 1444, 1267, 1180, 966, 737 cmꢁ1; H
NMR (300 MHz, CDCl3, TMS): d 1.80–1.95 (1H, m,
CH2), 1.98–2.14 (1H, m, CH2), 2.27 (6H, s, CH3), 2.45–
2.59 (2H, m, CH2), 2.82–3.01 (2H, m, CH2), 7.06 (2H,
d, J¼8.1 Hz, ArH), 7.12 (2H, d, J¼8.1 Hz, ArH), 7.29
(2H, d, J¼8.4 Hz, ArH), 7.64 (2H, d, J¼8.4 Hz, ArH);
4. Experimental procedures
4.1. General methods
13C NMR (75 MHz, CDCl3, TMS):
d 15.9, 20.9,
21.4, 32.3, 56.7, 125.4, 128.7, 129.6, 139.8, 131.5, 135.9,
140.3, 142.8, 200.8; MS (EI) m/z (%): 264 (8.11) [M+],
236 (3.53), 145 (83.75), 119 (100.00), 105 (10.19),
91 (48.04), 77 (2.87), 65 (19.59), 51 (4.53); HRMS (EI)
Calcd for C19H20O (M+) requires 264.1514, Found:
264.1513.
1H and 13C NMR spectra were recorded on a Bruker AM-
300 spectrometer for solution in CDCl3 with tetramethyl-
silane (TMS) as an internal standard; J values are given in
Hertz. Mass spectra were recorded by EI methods and
HRMS were measured on a Finnigan MA+ mass spectrome-
ter. CHN microanalyses were recorded on a Carlo-Erba 1106
analyzer. Solvents were used without further drying up.
Commercially obtained reagents were used without further
purification. All reactions were monitored by TLC with
Huanghai GF254 silica gel coated plates. Flash column chro-
matography was carried out using 300–400 mesh silica gel at
increased pressure.
4.2.4. (4-Fluorophenyl)(1-(4-fluorophenyl)cyclobutyl)-
methanone (2d). A colorless oil; IR (CH2Cl2): n 3072,
2988, 2948, 2870, 1888, 1675, 1598, 1508, 1410, 1268,
1156, 967, 833, 778 cmꢁ1; H NMR (300 MHz, CDCl3,
1
TMS): d 1.84–2.03 (1H, m, CH2), 2.06–2.16 (1H, m, CH2),
2.43–2.57 (2H, m, CH2), 2.85–2.99 (2H, m, CH2), 6.92–
7.09 (4H, m, ArH), 7.30–7.39 (2H, m, ArH), 7.69–7.78
(2H, m, ArH); 13C NMR (75 MHz, CDCl3, TMS): d 15.8,
32.3, 56.4, 115.3 (d, JC–F¼21.2 Hz), 115.9 (d, JC–F
¼
4.2. General procedure for rearrangement reaction of
vinylidenecyclopropanes with silver acetate and iodine
21.2 Hz), 127.2 (d, JC–F¼8.0 Hz), 130.2 (d, JC–F¼2.8 Hz),
132.3 (d, JC–F¼9.2 Hz), 138.7 (d, JC–F¼3.5 Hz), 161.6 (d,
JC–F¼258.2 Hz), 164.9 (d, JC–F¼267.9 Hz), 199.3; MS (EI)
m/z (%): 272 (3.18) [M+], 244 (3.24), 149 (89.13), 123
(100.00), 101 (30.52), 95 (68.88), 75 (38.32), 69 (6.17), 51
(10.49); HRMS (EI) Calcd for C17H14OF2 (M+) requires
272.1013, Found: 272.1000.
Under ambient atmosphere, methylenecyclobutanes (MCBs)
(0.4 mmol), AgOAc (1.2 mmol), and I2 (0.6 mmol) were
added into a Schlenk tube. The reaction mixture was stirred
at room temperature until the reaction completed. Then, the
solvent was removed under reduced pressure and the residue
was purified by a flash column chromatography (SiO2) to
give the corresponding products 2 in moderate to good yields.
4.2.5. (4-Methoxyphenyl)(1-(4-methoxyphenyl)cyclobu-
tyl)methanone (2e). A colorless oil; IR (CH2Cl2): n 3056,
2948, 2867, 2837, 1875, 1672, 1610, 1505, 1512, 1441,
4.2.1. Phenyl(1-phenylcyclobutyl)methanone (2a). A col-
orless oil; IR (CH2Cl2): n 3058, 3019, 2986, 2945, 2853,
1245, 1170, 1031, 968, 736 cmꢁ1 1H NMR (300 MHz,
;
CDCl3, TMS): d 1.80–1.95 (1H, m, CH2), 1.98–2.14 (1H,
m, CH2), 2.43–2.55 (2H, m, CH2), 2.83–2.97 (2H, m,
CH2), 3.74 (3H, s, CH3), 3.75 (3H, s, CH3), 6.76 (2H, d,
J¼8.4 Hz, ArH), 6.86 (2H, d, J¼8.4 Hz, ArH), 7.32 (2H,
d, J¼9.0 Hz, ArH), 7.73 (2H, d, J¼9.0 Hz, ArH); 13C
NMR (75 MHz, CDCl3, TMS): d 15.9, 32.4, 55.1, 55.2,
56.2, 113.3, 114.2, 126.7, 126.9, 132.0, 135.6, 158.0,
162.6, 200.8; MS (EI) m/z (%): 296 (9.72) [M+], 268
(4.35), 161 (100.00), 135 (69.25), 107 (7.29), 92 (8.43), 64
(5.92), 55 (3.12), 43 (4.51); HRMS (EI) Calcd for
C19H20O3 (M+) requires 296.1412, Found: 296.1403.
1
1675, 1598, 1579, 1495, 1250, 1179, 957, 700 cmꢁ1; H
NMR (300 MHz, CDCl3, TMS): d 1.80–1.97 (1H, m, CH2),
1.99–2.18 (1H, m, CH2), 2.16–2.62 (2H, m, CH2), 2.85–
3.03 (2H, m, CH2), 7.20–7.44 (8H, m, ArH), 7.65–7.75
(2H, m, ArH); 13C NMR (75 MHz, CDCl3, TMS): d 15.9,
32.2, 57.1, 125.6, 126.5, 128.1, 128.9, 129.7, 132.2, 134.1,
143.1, 201.0; MS (EI) m/z (%): 257 (1.39) [M+], 131
(46.17), 105 (100.00), 91 (15.75), 77 (43.53), 51 (11.17),
41 (1.84); HRMS (EI) Calcd for C17H16O (M+) requires
236.1201, Found: 236.1208.
4.2.2. (4-Chlorophenyl)(1-(4-chlorophenyl)cyclobutyl)-
methanone (2b). A white solid, mp 82–84 ꢀC; IR
(CH2Cl2): n 3058, 2987, 2947, 2869, 1677, 1587, 1569,
1490, 1399, 1251, 1093, 967, 752 cmꢁ1; 1H NMR (300 MHz,
CDCl3, TMS): d 1.85–2.03 (1H, m, CH2), 2.05–2.14 (1H, m,
CH2), 2.44–2.57 (2H, m, CH2), 2.62–3.02 (2H, m, CH2),
7.22–7.33 (6H, m, ArH), 7.59–7.68 (2H, m, ArH); 13C
NMR (75 MHz, CDCl3, TMS): d 15.9, 32.1, 56.6, 127.0,
128.6, 129.2, 131.0, 132.2, 132.6, 138.8, 141.4, 199.3; MS
(EI) m/z (%): 304 (2.27) [M+], 241 (2.58), 165 (59.97), 139
(100.00), 111 (19.62), 102 (11.09), 75 (16.38), 51 (5.51),
41 (1.62); HRMS (EI) Calcd for C17H14OCl2 (M+) requires
304.0422, Found: 304.0410.
4.2.6. (1-(4-Chlorophenyl)cyclobutyl)(phenyl)meth-
anone and (4-chlorophenyl)(1-phenylcyclobutyl)meth-
anone (2f). A colorless oil; IR (CH2Cl2): n 3058, 2987,
2946, 2868, 1978, 1894, 1675, 1587, 1490, 1399, 1250,
1
1176, 966, 824, 780 cmꢁ1; H NMR (300 MHz, CDCl3,
TMS): d 1.83–1.99 (1H, m, CH2), 2.01–2.17 (1H, m,
CH2), 2.45–2.58 (2H, m, CH2), 2.83–2.97 (2H, m, CH2),
7.15–7.44 (7H, m, ArH), 7.64–7.70 (2H, m, ArH); 13C
NMR (75 MHz, CDCl3, TMS): d 15.92, 15.96, 32.1, 32.3,
56.7, 57.0, 125.5, 126.7, 127.1, 128.1, 128.2, 128.5, 129.0,
129.1, 129.7, 131.1, 132.3, 132.41, 132.49, 133.7, 141.7,
142.8, 199.8, 200.7; MS (EI) m/z (%): 270 (2.10) [M+],
242 (1.02), 139 (36.81), 131 (100.00), 111 (21.04), 103
(59.58), 91 (23.60), 77 (28.11), 51 (15.58); HRMS (EI)
Calcd for C17H14OCl (M+) requires 270.0811, Found:
270.0816.
4.2.3. p-Tolyl(1-p-tolylcyclobutyl)methanone (2c). A col-
orless oil; IR (CH2Cl2): n 3024, 2986, 2945, 2867, 1672,

M. Jiang et al. / Tetrahedron 63 (2007) 9599–9604
9603
4.2.7. (1-(3,4-Dimethylphenyl)cyclobutyl)(phenyl)metha-
none and (3,4-dimethylphenyl)(1-phenylcyclobutyl)me-
thanone (2g). A colorless oil; IR (CH2Cl2): n 3058, 2943,
2864, 1675, 1598, 1504, 1447, 1250, 1180, 967, 818,
703 cmꢁ1; 1H NMR (300 MHz, CDCl3, TMS): d 1.82–2.02
(1H, m, CH2), 2.04–2.12 (1H, m, CH2), 2.20 (3H, s, CH3),
2.22 (3H, s, CH3), 2.47–2.59 (2H, m, CH2), 2.82–2.96 (2H,
m, CH2), 6.99–7.43 (6H, m, ArH), 7.74 (2H, d, J¼7.5 Hz,
ArH); 13C NMR (75 MHz, CDCl3, TMS): d 16.0, 18.8,
19.3, 19.7, 19.8, 19.9, 32.3, 38.2, 56.7, 57.1, 122.8, 125.5,
126.4, 127.0, 127.6, 128.1, 128.9, 129.2, 129.7, 130.1,
130.9, 131.9, 132.2, 134.2, 134.8, 136.5, 137.2, 140.5,
141.7, 143.5, 201.0, 201.3; MS (EI) m/z (%): 264 (8.04)
[M+], 236 (4.16), 159 (100.00), 131 (79.89), 105 (29.64),
77 (36.26), 51 (12.51), 41 (3.64); HRMS (EI) Calcd for
C19H20O (M+) requires 264.1514, Found: 264.1525.
m, CH2), 2.66–2.78 (2H, m, CH2), 7.10–7.16 (4H, m,
ArH); 13C NMR (75 MHz, CDCl3, TMS): d 13.8, 15.9,
20.9, 22.3, 23.8, 30.4, 31.2, 36.3, 58.6, 126.2, 129.2,
136.2, 140.1, 211.1; MS (EI) m/z (%): 244 (1.60) [M+],
145 (100.00), 117 (78.57), 115 (16.76), 105 (11.17), 91
(12.06), 43 (18.68), 41 (10.48); HRMS (EI) Calcd for
C17H24O (M+) requires 244.1827, Found: 244.1827.
Acknowledgements
We thank the Shanghai Municipal Committee of Science and
Technology (04JC14083 and 06XD14005) and the National
Natural Science Foundation of China for financial support
(203900502, 20472096, and 20672127). We also appreciate
Dr. Yu-Xue Li’s help on computational calculation on 13C
chemical shifts.
4.2.8. 1-(1-p-Tolylcyclobutyl)ethanone (2i). A colorless
oil; IR (CH2Cl2): n 2945, 2865, 1706, 1512, 1430, 1352,
1246, 1189, 1107, 827, 815 cmꢁ1
;
1H NMR (300 MHz,
Supplementary data
CDCl3, TMS): d 1.83–1.93 (2H, m, CH2), 1.92 (3H, s, CH3),
2.34 (3H, s, CH3), 2.32–2.45 (2H, m, CH2), 2.66–2.78 (2H,
m, CH2), 7.10–7.26 (4H, m, ArH); 13C NMR (75 MHz,
CDCl3, TMS): d 15.8, 21.0, 24.3, 30.4, 58.9, 126.1, 129.3,
136.3, 140.1, 209.0; MS (EI) m/z (%): 188 (4.87) [M+], 160
(2.04), 145 (72.35), 117 (100.00), 105 (14.56), 91 (19.25),
77 (6.06), 63 (20.24), 43 (25.98); HRMS (EI) Calcd for
C13H16O (M+) requires 188.1201, Found: 188.1194.
It includes 1H and 13C NMR spectroscopic charts for com-
pounds 2a–2l. This material is available free of charge via
the Internet. Supplementary data associated with this article
can be found in the online version, at doi:10.1016/
j.tet.2007.07.046.
References and notes
4.2.9. 1-(1-(4-Bromophenyl)cyclobutyl)ethanone (2j). A
colorless oil; IR (CH2Cl2): n 2986, 2944, 1894, 1705,
1. (a) Gunstone, F. D.; Morris, L. J. J. Chem. Soc. 1957, 487–489;
(b) Wiberg, K. B.; Saegebarth, K. A. J. Am. Chem. Soc. 1957,
79, 6256–6258; (c) Erfan Ali, M.; Owen, L. N. J. Chem. Soc.
1958, 1074–1076.
2. (a) Zingaro, R. A.; Goodrich, J. E.; Kleinberg, J.; Vanderwerf,
C. A. J. Am. Chem. Soc. 1949, 71, 575–576; (b) Bogert, B.
J. Am. Chem. Soc. 1943, 65, 1075–1078.
3. (a) Shi, M.; Liu, L. P.; Tang, J. Org. Lett. 2005, 7, 3085–3088;
(b) Shao, L. X.; Zhao, L. J.; Shi, M. Eur. J. Org. Chem. 2004,
4894–4900; (c) Xu, B.; Shi, M. Org. Lett. 2003, 5, 1415–1418.
4. Huang, X.; Zhou, H. W. J. Org. Chem. 2004, 69, 839–842,
1015–1026.
1487, 1427, 1394, 1352, 1189, 1074, 1009, 831, 698 cmꢁ1
;
1H NMR (300 MHz, CDCl3, TMS): d 1.76–1.92 (2H, m,
CH2), 1.93 (3H, s, CH3), 2.31–2.44 (2H, m, CH2), 2.68–
2.79 (2H, m, CH2), 7.12 (2H, d, J¼8.7 Hz, ArH), 7.48
(2H, d, J¼8.7 Hz, ArH); 13C NMR (75 MHz, CDCl3,
TMS): d 15.8, 24.3, 30.4, 58.8, 120.7, 128.0, 131.7, 142.1,
207.9; MS (EI) m/z (%): 252 (5.81) [M+], 209 (90.83), 183
(68.34), 173 (22.09), 130 (93.11), 102 (84.44), 75 (25.53),
63 (13.14), 43 (100); HRMS (EI) Calcd for C12H13OBr
(M+) requires 252.0150, Found: 252.0157.
4.2.10. 1-(1-(4-(Trifluoromethyl)phenyl)cyclobutyl)etha-
none (2k). A colorless oil; IR (CH2Cl2): n 2947, 2856, 1709,
5. For the synthesis of MCBs (the procedures are the same as
MCPs), see: Brandi, A.; Goti, A. Chem. Rev. 1998, 98, 589–636.
6. (a) Graham, S. H.; William, A. J. S. J. Chem. Soc. 1959, 4066–
4072; (b) Farcasiu, D.; Schleyer, P. V. R.; Ledlie, D. J. Org.
Chem. 1973, 38, 3455–3459; (c) Graham, S. H.; William,
A. J. S. J. Chem. Soc. C 1966, 655–660; (d) Fitjer, L.;
Kanschik, A.; Majewski, M. Tetrahedron Lett. 1988, 29,
5525–5528; (e) Shen, Y. M.; Wang, B.; Shi, Y. Angew.
Chem., Int. Ed. 2002, 45, 1429–1432.
1593, 1489, 1354, 1332, 1225, 1125, 1075, 902, 705 cmꢁ1
;
1H NMR (300 MHz, CDCl3, TMS): d 1.83–1.98 (2H, m,
CH2), 1.95 (3H, s, CH3), 2.37–2.50 (2H, m, CH2), 2.73–2.86
(2H, m, CH2), 7.38–7.56 (4H, m, ArH); 13C NMR (75 MHz,
CDCl3, TMS): d 15.9, 24.4, 30.6, 59.1, 122.8 (q, JC–F
¼
4.5 Hz), 123.6 (q, JC–F¼3.8 Hz), 124.0 (q, JC–F¼270.6 Hz),
129.2, 129.7 (q, JC–F¼1.2 Hz), 131.1 (q, JC–F¼32.0 Hz),
144.2, 207.6; MS (EI) m/z (%): 242 (3.63) [M+], 199
(100.00), 171 (40.53), 159 (20.69), 145 (10.01), 130 (8.19),
117 (6.59), 91 (1.53), 43 (93.90); HRMS (EI) Calcd for
C13H13OF3 (M+) requires 242.0918, Found: 242.0922.
7. The crystal data of 2b have been deposited in CCDC with num-
ber 638150. Empirical formula: C17H14Cl2O; formula weight:
305.18; crystal color, habit: colorless, prismatic; crystal dimen-
sions: 0.507ꢂ0.482ꢂ0.176 mm; crystal system: triclinic; lat-
˚
tice type: primitive; lattice parameters: a¼6.3238(11) A,
b¼10.3449(17) A, c¼11.8736(19) A, a¼79.549(3)ꢀ, b¼
˚
˚
4.2.11. 1-(1-(4-(Trifluoromethyl)phenyl)cyclobutyl)-
hexan-1-one (2l). A colorless oil; IR (CH2Cl2): n 3021,
2955, 2861, 1706, 1512, 1459, 1378, 1355, 1168, 1085,
3
ꢀ
ꢀ
˚
78.145(3) , g¼80.998(3) , V¼741.8(2) A ; space group: P-1;
Z¼2; Dcalc¼1.366 g/cm3; F000¼316; diffractometer: Rigaku
AFC7R; residuals: R; Rw: 0.0502, 0.1269.
1
1018, 814, 727 cmꢁ1; H NMR (300 MHz, CDCl3, TMS):
d 0.80 (3H, t, J¼7.2 Hz, CH3), 1.01–1.35 (4H, m, CH2),
1.38–1.46 (2H, m, CH2), 1.77–1.92 (2H, m, CH2), 2.20
(2H, t, J¼7.2 Hz, CH2), 2.33 (3H, s, CH3), 2.30–2.45 (2H,
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