Facile preparation of cyclopropanes from 2-iodoethyl-substituted olefins and 1,3-dihalopropanes with zinc powder

Article abstract of DOI:10.1016/j.tet.2005.07.103

Two efficient, simple, cheap, and environmentally benign preparations of cyclopropanes were achieved. One is the formation via 3-exo-trig manner from various electron-deficient 2-iodoethyl-substituted olefins with zinc powder in a mixture of t-butyl alcoh

Full text of DOI:10.1016/j.tet.2005.07.103

Tetrahedron 61 (2005) 10138–10145
Facile preparation of cyclopropanes from 2-iodoethyl-substituted
olefins and 1,3-dihalopropanes with zinc powder
Daisuke Sakumaa and Hideo Togoa,b,
*
aGraduate School of Science and Technology, Chiba University, Yayoi-cho 1-33, Inage-ku, Chiba 263-8522, Japan
bDepartment of Chemistry, Faculty of Science, Chiba University, Yayoi-cho 1-33, Inage-ku, Chiba 263-8522, Japan
Received 7 June 2005; accepted 7 July 2005
Abstract—Two efficient, simple, cheap, and environmentally benign preparations of cyclopropanes were achieved. One is the formation via
3-exo-trig manner from various electron-deficient 2-iodoethyl-substituted olefins with zinc powder in a mixture of t-butyl alcohol and water,
and the other is the formation via 3-exo-tet manner from various 1,3-dihalopropanes with zinc powder in ethanol.
q 2005 Published by Elsevier Ltd.
1. Introduction
typical radical reagent system, Bu3SnH with AIBN in
refluxing benzene, Jung reported an interesting study in that
the introduction of a gem-dialkoxy group to the 5-position
of 6-bromo-2-hexenoate esters dramatically promoted
radical 4-exo-trig cyclization to provide the corresponding
cyclobutanes (a-cyclobutylacetate esters).9 Based on this
result, methyl 5-bromo-4,4-dimethoxy-2-pentenoate was
treated with Bu3SnH and AIBN in refluxing benzene.
However, the expected cyclopropane derivative was not
formed,10 since ring-opening reaction of the formed
cyclopropylmethyl radical occurred rapidly. On the other
hand, electrochemical reductive cyclization of ethyl
5-methanesulfonyloxy-4,4-dimethyl-2-pentenoate was
effectively carried out to form the corresponding cyclo-
propane.11 Photolysis of 2-substituted butyrophenones gave
the corresponding cyclopropyl phenyl ketones through a
Norrish II type pathway.12 As metal-induced radical 3-exo-
trig cyclization, formation of 11b-hydroxy-5,9-cyclo-
pregnane-3,20-dione by SET reduction of 9a-bromo-11b-
hydroxyprogestrone bearing a d-bromo-a,b-unsaturated
ketone group, with chromous acetate was reported.13
Treatment of d-iodo- and d-bromo-a,b-unsaturated esters
with SmI2 in the presence of t-butyl alcohol in THF gave the
corresponding cyclopropanes.14 The same treatment of g,g-
disubstituted d-oxo-a,b-unsaturated esters with SmI2 in the
presence of t-butyl alcohol in THF provided the correspond-
ing cyclopropanols via the ketyl radicals.15 Among these
cyclopropanation methods, SmI2-mediated radical 3-exo-
trig cyclization to cyclopropanes is effective and useful.
However, SmI2 is extremely air-sensitive and, therefore,
careful experimental operation is required. For the radical
3-exo-dig cyclization, the cyclization generally does not
proceed. This is in agreement with Baldwin’s rule, since
A wide variety of naturally occurring cyclopropane
derivatives bearing potent utility and biological activity
are known.1 Therefore, synthetic study of the cyclopropane
ring is still important. Practical methods for the construction
of cyclopropanes with olefinic groups have been carried out
with free carbene derived from haloform under basic
conditions,2 diazo-olefins with the Rh-catalyst,3 the
Simmons–Smith reactions4 and others.5 Among them,
cyclopropanation with diazo-olefins using the Rh-catalyst
and the Simmons–Smith reaction are the most common and
useful. However, generally, electron-rich olefins are
required, since these reactions proceed via an electrophilic
manner. On the other hand, the formation of cyclopropanes
via radical pathways is challenging and interesting, since the
cyclopropane rings are thermodynamically much dis-
favoured because of their ring strain,6 and the carbon-
centered radicals are generally nucleophilic, and, therefore,
electron-deficient olefins are required.7 There are three
approaches for the construction of cyclopropane rings
through a radical pathway. The first one is the formation
of cyclopropanes via radical 3-exo-trig cyclization, the
second one is that via radical 3-exo-dig cyclization, and the
third one is that via radical 3-exo-tet cyclization. Today, to
the best of our knowledge, studies on the formation of
cyclopropanes via radical pathways are extremely limited,
though a few radical 3-exo-trig cyclizations, which are
favoured in Baldwin’s rule, are known.8 Thus, for the
Keywords: Cyclopropane; 3-exo-trig; 3-exo-tet; Zinc.
*
Corresponding author. Address: Graduate School of Science and
Technology, Chiba University, Yayoi-cho 1-33, Inage-ku, Chiba 263-
8522, Japan. Fax: C81 43 290 2874; e-mail: togo@faculty.chiba-u.jp
0040–4020/$ - see front matter q 2005 Published by Elsevier Ltd.
doi:10.1016/j.tet.2005.07.103

D. Sakuma, H. Togo / Tetrahedron 61 (2005) 10138–10145
Table 1. 3-exo-trig Cyclization of benzyl 5-halo-4,4-dimethyl-2-pentenoate
10139
Entry
X
Reagent
Additive
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
Bra
Zn
Zn
Zn
Zn
Zn
Zn
Zn
Zn
—
—
—
—
6
18
5
4
4
2
3
3
2
4
10
9
1
2
15
Brb
42 (37)c
0
67
Brd
Ia
I
I
I
I
I
I
I
I
I
I
—
77
63
21
67
ZnBr2
Yb(OTf)3
FeCl3
Mg(ClO4)2
—
—
—
—
—
e
9
Zn
In
Mg
Fe
Bu3SnHf
(Me3Si)3SiHh
76
10
11
12
13
14
17 (26)c
0 (83)c
0 (86)c
0 (83)g
0 (36)g
a A mixture of t-amyl alcohol and H2O (2:1) was used as a solvent, instead of a mixture of t-BuOH and H2O (2:1).
b KI (2.0 equiv) was added.
c Yield of recovered starting material 1a.
d Sonication was carried out at 40 8C in an ultrasonic cleaner bath.
e Mg(ClO4)2 (2.0 equiv) was added.
f
A mixture of Bu3SnH (1.5 equiv) and AIBN (0.3 equiv) in t-BuOH was added dropwise over 1 h.
g Yield of compound 3a,
h A mixture of (Me3Si)3SiH (1.5 equiv) and AIBN (0.5 equiv) in t-BuOH was added dropwise over 2 h.
(3a).
3-exo-dig cyclization is disfavoured. For the radical 3-exo-
tet cyclization, the study is extremely limited, though
radical 3-exo-tet cyclization is favoured in Baldwin’s rule.8
1,3-Dihalides, mainly 1,3-diiodopropane derivatives, can be
reductively cyclized to cyclopropanes by metal reduction
such as Na,16a–c halogen–metal exchange such as t-BuLi,17
and metal hydride such as LiAlH4,16b,c and it is proposed
that some of these reactions proceed through a radical
pathway. Treatment of 1,3-diiodopropane with benzoyl
peroxide at 110 8C gave cyclopropane in quite good yield.18
Treatment of 2,2-disubstituted 1,3-diiodopropane with
Bu3SnH in refluxing benzene gave the corresponding
cyclopropane in good yield.16c Recently, an interesting
study for the formation of substituted cyclopropanes from
the reaction of 2-substituted 1,3-diiodopropanes with
(C6F13CH2CH2)3SnH or Ph3SnH and AIBN under highly
diluted conditions through homolytic substitution of the
intermediate 3-iodoalkyl radicals was reported, and radical
2. Results and discussion
2.1. Formation of cyclopropanes from 2-haloethyl-
substituted olefins via 3-exo-trig manner
As a preliminary study, benzyl 5-bromo-4,4-dimethyl-2-
pentenoate (1a–i) and benzyl 5-iodo-4,4-dimethyl-2-pen-
tenoate (1a–ii) were treated with zinc powder in a mixture
of t-butyl alcohol and water under refluxing conditions as
shown in Table 1. Reactivity of the bromide 1a–i was poor
(entries 1–3), even though the reaction was carried out in the
presence of KI or under sonication conditions, and the
starting material was recovered mainly. However, the iodide
1a–ii showed good reactivity to give the corresponding
cyclopropane, benzyl (2,2-dimethylcyclopropyl)acetate, in
cyclization proceeds in the range of 5!105 sK1 19
.
Previously, we reported zinc- and indium-mediated radical
ring-expansion reaction of a-halomethyl cyclic b-keto
esters in aqueous alcohol to give the corresponding ring-
expanded products in good yields, as an environmentally
benign method.20h Here, as a part of our study toward
environmentally benign organic synthesis via a radical
pathway,20 we would like to report an efficient, simple,
cheap, and environmentally benign zinc-mediated radical
3-exo-trig cyclization of electron-deficient 2-haloethyl-
substituted olefins to provide cyclopropanes in a mixture
of t-butyl alcohol and water, and zinc-mediated 3-exo-tet
cyclization of 1,3-dihalopropanes to provide cyclopropanes
in ethanol.21
Scheme 1. Plausible reaction pathway.

10140
D. Sakuma, H. Togo / Tetrahedron 61 (2005) 10138–10145
Table 2. 3-exo-trig Cyclization of 2-iodoethyl-subtituted olefins
Entry
1
Substrate
Time (h)
5
Product
Yield (%)
5 (2b)
2
3
4
3
1
4
6 (2c)
13 (2d)
77 (2a)
5
6
7
3
99 (2e)
55 (2f)a
84 (2g)
0.5
3
8
9
4
2
75 (2h)
62 (2i)
10
11
2
2
66 (2j)b
90 (2k)
12
13
3
1
0 (64)c
0 (70)c
14
2
0 (88)c
a Compound 5f was also obtained in 35% yield
(5f).
b Syn/antiZ2:1.
c Yield of the direct reduction product.
good yield (entry 5). The addition of a Lewis acid for
activation of the olefinic group by coordination onto the
carbonyl oxygen atom of the iodide 1a–ii, did not affect the
yield (entries 6–9). Instead of zinc powder, the addition of
indium showed poor reactivity (entry 10), and magnesium
and iron powder did not provide any cyclized product
(entries 11, 12). As typical radical reagents, tributyltin
hydride and tris(trimethylsilyl)silane were treated with
iodide 1a–ii in the presence of AIBN, respectively.
However, the cyclized cyclopropane 2a was not obtained
at all; instead, indirect reduction product 3a was obtained in
83 and 36% yields, respectively (entries 13, 14). This result
supports Jung’s report.10 Radical cyclization of primary
carbon-centered radical A via 3-exo-trig manner is rapid,
however, ring opening of the cyclized cyclopropylmethyl
radical B is more rapid than the ring closure to generate a
more stable tertiary carbon-centered radical C, as shown in
Scheme 1. It is known that the rate constant for ring opening

D. Sakuma, H. Togo / Tetrahedron 61 (2005) 10138–10145
10141
of a cyclopropylmethyl radical is 1.3!108 sK1 (25 8C), and
that of the ring closure via 3-exo-trig manner is 1.0!104 sK1
(25 8C).22 The rate constants for the hydrogen atom
abstraction from tributyltin hydride and tris(trimethylsilyl)-
silane by a primary carbon-centered radical are 2.4!
106 MK1 sK1 (25 8C) and 3.8!105 MK1 sK1 (25 8C),
respectively.23 Therefore, in tributyltin hydride and tris-
(trimethylsilyl)silane systems, before the hydrogen atom
abstraction from them by the cyclized cyclopropylmethyl
radical B, ring opening rapidly occurred to give the indirect
reduction product 3a through the hydrogen atom abstraction
by stable tertiary carbon-centered radical C. However, with
zinc powder, the cyclized carbon-centered radical B is
rapidly reduced to the corresponding anion and is
protonated to provide cyclopropane, benzyl (2,2-dimethyl-
cyclopropyl)acetate, in good yield.
effectively to form the corresponding cyclopropanol in
good yield (entry 11).
2.2. Formation of cyclopropanes from 1,3-dihalo-
propanes via 3-exo-tet manner
Reaction of compound 6a with zinc powder (3.0 equiv) was
carried out in refluxing mixtures of t-BuOH/H2O and EtOH/
H2O to give the corresponding cyclopropane 7a in 93 and
98% yields, respectively, as shown in Table 3 (entries 1, 2).
When the amount of zinc powder was reduced to 1.2 equiv,
the reaction also proceeded under the same conditions.
However, the yield was decreased and the starting material
6a was partly recovered (entry 3). The reaction in refluxing
EtOH proceeded again cleanly, even though the amount of
zinc powder was reduced to 1.2 equiv (entry 4). When the
reaction was carried out in EtOH or in a mixture of EtOH/
H2O at room temperature, cyclopropane 7a was not formed
at all, and the starting material 6a was recovered
quantitatively (entries 5, 6). On the other hand, the reaction
in a mixture of THF/satd aq NH4Cl at room temperature
proceeded, though the reaction requires long reaction time
and 3.0 equiv of zinc powder for effective cyclization
(entries 7, 8). Instead of zinc powder, the addition of indium
powder showed poor reactivity (entry 11), and magnesium
and iron powder did not provide any cyclopropane 7a
(entries 9, 10). As typical radical reagents, Bu3SnH and
(Me3Si)3SiH were treated with 1,3-diiodopropane 6a in the
presence of AIBN in refluxing EtOH to give cyclopropane
7a in 99 and 22% yields, respectively (entries 12–14).
Additionally, as a typical SET reagent, SmI2 was treated
with 1,3-diiodopropane 6a in THF at room temperature to
give cyclopropane 7a in good yield (entry 15).
Based on these results, various 2-iodoethyl-substituted
olefins were treated with zinc powder under the same
conditions as shown in Table 2. Thus, electron-withdrawing
groups such as ester, ketone, amide, sulfone, and nitro
groups accelerate the radical 3-exo-trig cyclization to give
the corresponding cyclopropanes effectively (entries 4–10),
while phenyl and pentyl groups did not provide any cyclized
products at all, respectively (entries 12, 13). Moreover, it is
obvious that the introduction of dialkyl groups to the
4-position or 5-position of 5-iodo-2-pentenoate esters
promotes the radical 3-exo-trig cyclization, while, the
introduction of a monoalkyl group to the 4- or 5-position
of 5-iodo-2-pentenoate esters reduces dramatically the
cyclization product, similar to the parent 5-iodo-2-penteno-
ate esters (entries 1–6). This is the same effect, which was
observed for the radical 4-exo-trig cyclization of 6-bromo-
2-hexenoate ester with Bu3SnH.9 Thus, introduction of two
alkyl groups to the 4- or 5-position of 2-pentenoate esters is
important for the efficient 3-exo-trig cyclization. Instead of
an activated olefinic group, radical 3-exo-trig cyclization
onto an electron-deficient formyl group proceeded
Based on these results, various 1,3-diiodopropanes 6
bearing methoxy, bromo, ester, and olefinic groups were
treated with zinc powder to provide the corresponding
cyclopropanes 7 in good yields as shown in Table 4. Thus,
1,3-diiodopropanes bearing dibenzyl, bis-p-methylbenzyl,
Table 3. Cyclization of 2,2-dibenzyl-1,3-diiodopropane with zinc powder
Entry
Reagent
A
Solvent
Condition
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
Zn
Zn
Zn
Zn
Zn
Zn
Zn
Zn
3.0
3.0
1.2
1.2
1.2
1.2
3.0
1.2
1.2
1.2
1.2
2.4
2.4
2.4
3.0
t-BuOH/H2O (2:1)
EtOH/H2O (2:1)
EtOH/H2O (2:1)
EtOH
EtOH
EtOH/H2O (3:1)
aq NH4Cl (satd)/THF (1:1)
aq NH4Cl (satd)/THF (1:1)
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
THF
Reflux
Reflux
Reflux
Reflux
rt
rt
rt
rt
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
rt
1
2
3
3
22
24
24
24
21
18
6
93
98
60 (36)a
97
0 (97)a
0 (99)a
92
43 (46)a
0 (99)a
0 (94)a
10 (68)a
99
9
Fe
Mg
In
10
11
12
13
14
15
Bu3SnHb
Bu3SnH
(Me3Si)3SiHc
SmI2
5
3
4
1
99
22
83
a Yield of recovered starting material 6a.
b A mixture of Bu3SnH (2.4 equiv) and AIBN (0.2 equiv) in EtOH was added dropwise over 4 h.
c A mixture of (Me3Si)3SiH (2.4 equiv) and AIBN (0.2 equiv) in EtOH was added dropwise over 3 h.

10142
D. Sakuma, H. Togo / Tetrahedron 61 (2005) 10138–10145
Table 4. Cyclization of various 1,3-dihalopropane with zinc powder
Entry
1
Substrate
Time (h)
3
Yield (%)
97
(a)
2
3
4
5
1
3
3
5
99
96
91
86
(b)
(c)
(d)
(e)
6
7
XZI (f)
XZBr (f–i)
2
98
81
15a
8
9
XZI (g)
XZBr (g–i)
1
15a
99
83 (5)b
10
11
12
XZI (h)
XZBr (h–i)
XZCl (h–ii)
2
94
76
27
15a
18a
13
14
XZI (i)
XZI (j)
2
2
16a
94
98
46 (45)c
15
XZBr (j–i)
16
XZI (k)
3
93 (1:0.8)d
17
18
XZI (k)
XZI (k)
5e
5f
29 (61)c
(1:2)d
42 (47)c
(1:2)d
a Zn (3.0 equiv) and NaI (3.0 equiv) were added.
b Yield of recovered starting material 6g–i.
c Yield of direct reduction product.
d Ratio of diastereomers.
e A mixture of Bu3SnH (2.4 equiv) and AIBN (0.2 equiv) in EtOH was added dropwise over 4 h.
f
A mixture of (Me3Si)3 SiH (2.4 equiv) and AIBN (0.2 equiv) in EtOH was added dropwise over 4 h.
bis-p-methoxybenzyl, bis-p-bromobenzyl, and diethoxy-
carbonyl groups at the 2-position, generated cyclopropanes
7 in good yields (entries 1–5). 1,3-Diiodopropanes bearing
p-bromobenzyl, dodecyl, and 10-undecenyl groups at the
2-position, and bearing dodecyl and 10-undecenyl groups at
the 1-position, also gave cyclopropanes in good yields
(entries 6, 8, 10, 13, 14). When 1,3-dibromopropanes were
treated in the presence of NaI under the same conditions, the
corresponding cyclopropanes were again formed in good
yields (entries 7, 9, 11). However, 1,3-dibromopropane
bearing a 10-undecenyl group at the 1-position gave the
cyclopropane in moderate yield (entry 15). This result
probably comes from the fact that the nucleophilic
substitution at the secondary carbon-bromine bond by the
iodide anion does not proceed effectively. When 1,3-
disubstituted 1,3-diiodopropane 6k, which is a diastereo-
meric mixture (2:5) was treated with zinc powder, Bu3SnH
initiated by AIBN, and (Me3Si)3SiH initiated by AIBN
under the same conditions, the corresponding cyclopropane
7k was obtained in good yield with zinc powder, in poor
yield with Bu3SnH, and in moderate yield with (Me3Si)3-
SiH, respectively, and the ratio of the diastereomers was a
little different (entries 16–18). The present cyclization
mechanism with zinc powder is still not clear, and it may not
be completely the same as that with Bu3SnH and (Me3Si)3-
SiH, that is, radical 3-exo-tet manner.
3. Conclusion
Thus, zinc-mediated cyclopropanation of electron-deficient
2-iodoethyl-substituted olefins in a mixture of t-butyl
alcohol and water, and zinc-mediated cyclopropanation of
1,3-dihalopropanes in ethanol were successfully achieved.
The present methods are efficient, simple, and environ-
mentally benign for the preparation of cyclopropanes.
4. Experimental
4.1. General
1H NMR spectra were recorded on 400 and 500 MHz
spectrometers, and 13C NMR spectra were recorded on 100

D. Sakuma, H. Togo / Tetrahedron 61 (2005) 10138–10145
10143
and 125 MHz spectrometers. Chemical shifts are expressed
in ppm downfield from TMS in d units. In the 13C NMR
spectra, p, s, t, and q means primary, secondary, tertiary,
quaternary. Mass spectra were recorded on HX-110 and
JMS-AT II 15 spectrometers. IR spectra were measured
with an FT/IR-200 spectrometer. Silica Gel 60 was used for
column chromatography, and Wakogel B-5F was used for
preparative TLC. Zinc powder (no. 48005-30) was obtained
from Kanto Kagaku Co, and used directly without any pre-
treatment.
(100 MHz, CDCl3) dZ200.3 (q), 137.0 (q), 132.8 (t),
128.5 (t), 128.0 (t), 39.2 (s), 27.1 (p), 20.2 (p), 19.8 (s), 19.6
(t), 15.4 (q); MS (FAB): m/z 189; HRMS (FAB) found:
189.1268 m/z, calcd for C13H17O: MCHZ189.1279.
4.2.5. 2-(20,20-Dimethylcyclopropyl)-1-piperidinyletha-
none (2h). Colorless oil; IR (neat) 2940, 1640, 1440,
1
1250, 1220 cmK1; H NMR (400 MHz, CDCl3) dZ3.56
(2H, dt, JZ5.3, 5.1 Hz), 3.40 (2H, m), 2.44 (1H, dd, JZ
15.5, 6.3 Hz), 2.24 (1H, dd, JZ15.5, 7.5 Hz), 1.68–1.50
(6H, m), 1.08 (3H, s), 1.05 (3H, s), 0.90–0.79 (1H, dddd, JZ
8.6, 7.5, 6.3, 4.7 Hz), 0.52 (1H, dd, JZ8.6, 4.7 Hz), 0.04
(1H, t, JZ4.7 Hz); 13C NMR (100 MHz, CDCl3) dZ171.4
(q), 46.8 (s), 42.7 (s), 34.0 (s), 27.1 (p), 26.6 (s), 25.6 (s),
24.6 (s), 20.5 (t), 20.2 (p), 19.8 (s), 15.4 (q); MS (FAB): m/z
196; HRMS (FAB) found: 196.1718 m/z, calcd for
C12H22O14N: MCHZ196.1701.
4.2. General procedure for zinc-mediated cyclopro-
panation of electron-deficient 2-iodoethyl-substituted
olefins
Zinc powder (1.2 mmol) was added to a refluxing solution
of 2-iodoethyl olefin (0.4 mmol) in a mixture of t-BuOH
(2 mL) and water (1 mL) under an argon atmosphere. After
0.5–5 h at the same temperature, the mixture was filtered
through Celitew, then the solvent was removed, and the
residue was purified by preparative TLC or column
chromatography on silica gel.
4.2.6.
(2,2-Dimethylcyclopropyl)methanesulfonyl-
benzene (2i). Colorless oil; IR (neat) 2950, 1300, 1150,
750, 690 cmK1; 1H NMR (400 MHz, CDCl3) dZ7.93 (2H,
m), 7.66 (1H, tt, JZ7.4, 1.5 Hz), 7.57 (2H, m), 3.22 (1H, dd,
JZ14.5, 7.0 Hz), 3.05 (1H, dd, JZ14.5, 7.2 Hz), 0.98 (3H,
s), 0.91–0.83 (1H, dddd, JZ8.7, 7.2, 7.0, 5.0 Hz), 0.78 (3H,
s), 0.52 (1H, dd, JZ8.7, 5.0 Hz), 0.00 (1H, t, JZ5.0 Hz);
13C NMR (100 MHz, CDCl3) dZ139.1 (q), 133.5 (t), 129.0
(t), 128.4 (t), 57.5 (s), 26.4 (p), 19.9 (p), 19.2 (s), 17.6 (t),
16.1 (q); MS (FAB): m/z 225; HRMS (FAB) found:
225.0935 m/z, calcd for C12H17O2S: MCHZ225.0949.
4.2.1. Benzyl (2,2-dimethylcyclopropyl)acetate (2a).
1
Colorless oil; IR (neat) 2950, 1740, 750, 700 cmK1; H
NMR (400 MHz, CDCl3) dZ7.40–7.28 (5H, m), 5.14 (2H,
s), 2.37 (2H, d, JZ7.6 Hz), 1.05 (3H, s), 1.02 (3H, s), 0.94–
0.84 (1H, m), 0.51 (1H, dd, JZ8.5, 4.6 Hz), 0.03 (1H, t, JZ
4.6 Hz); 13C NMR (100 MHz, CDCl3) dZ173.6 (q), 136.2
(q), 128.5 (t), 128.1 (t), 66.1 (s), 35.0 (s), 27.0 (p), 20.0 (p),
19.9 (t), 19.5 (s), 15.4 (q); MS (FAB): m/z 218; HRMS (EI)
found: 218.1297 m/z, calcd for C14H18O2: MCZ218.1307.
4.2.7. 2,2-Dimethyl cyclopropanecarbaldehyde oxime
1
(2j). H NMR (400 MHz, CDCl3) syn form: dZ6.68 (1H,
d, JZ8.6 Hz), 2.14 (1H, td, JZ8.6, 5.1 Hz), 1.18 (3H, s),
1.17 (3H, s), 0.96 (1H, dd, JZ8.6, 5.1 Hz), 0.65 (1H, t, JZ
5.1 Hz); anti form: dZ7.22 (2H, d, JZ8.5 Hz), 1.44 (1H, td,
JZ8.5, 5.1 Hz), 1.14 (6H, s), 0.84 (1H, dd, JZ8.5, 5.1 Hz),
0.66 (1H, t, JZ5.1 Hz).
4.2.2. Benzyl 2-spiro[2.5]octylacetate (2e). Colorless oil;
IR (neat) 2930, 1740, 750, 700 cmK1; 1H NMR (400 MHz,
CDCl3) dZ7.40–7.27 (5H, m), 5.14 (2H, s), 2.45 (1H, dd,
JZ16.3, 7.2 Hz), 2.34 (1H, dd, JZ16.3, 7.6 Hz), 1.58–1.12
(10H, m), 0.94–0.85 (1H, dddd, JZ8.5, 7.6, 7.2, 4.7 Hz),
0.48 (1H, dd, JZ8.5, 4.7 Hz), 0.03 (1H, t, JZ4.7 Hz); 13C
NMR (100 MHz, CDCl3) dZ173.4 (q), 136.1 (q), 128.4 (t),
128.1 (t), 128.0 (t), 66.0 (s), 37.5 (s), 34.1 (s), 30.6 (s), 26.3
(s), 25.6 (s), 25.4 (s), 22.8 (q), 19.5 (t), 17.8 (s); MS (FAB):
m/z 259; HRMS (FAB) found: 259.1679 m/z, calcd for
C17H23O2: MCHZ259.1698.
1
4.2.8. Spiro[2.5]octan-1-ol (2k). Colorless oil; H NMR
(400 MHz, CDCl3) dZ3.28 (1H, dd, JZ6.1, 3.0 Hz), 1.62–
1.38 (8H, m), 1.21–1.10 (2H, m), 0.47 (1H, t, JZ6.1 Hz),
0.33 (1H, dd, JZ6.1, 3.0 Hz); 13C NMR (100 MHz, CDCl3)
dZ56.5 (t), 34.7 (s), 28.8 (s), 26.3 (s), 25.9 (s), 25.0 (s), 24.3
(q), 20.2 (s).
4.2.3. Ethyl 2-spiro[2.5]octylacetate (2f). Colorless oil; IR
(neat) 2930, 1740, 1180 cmK1; 1H NMR (400 MHz, CDCl3)
dZ4.15 (2H, q, JZ7.2 Hz), 2.38 (1H, dd, JZ16.2, 7.3 Hz),
2.27 (1H, dd, JZ16.2, 7.3 Hz), 1.27 (3H, t, JZ7.2 Hz),
1.60–1.24 (10H, m), 0.91–0.81 (1H, m), 0.47 (1H, dd, JZ
8.4, 4.5 Hz), 0.01 (1H, t, JZ4.5 Hz); 13C NMR (100 MHz,
CDCl3) dZ173.8 (q), 60.2 (s), 37.6 (s), 34.2 (s), 30.7 (s),
26.4 (s), 25.6 (s), 25.1 (s), 22.8 (q), 19.5 (t), 17.8 (s), 14.2
(p); MS (FAB): m/z 197; HRMS (EI) found: 196.1467 m/z,
calcd for C12H20O2: MCZ196.1463.
4.3. General procedure for zinc-mediated cyclopropa-
nation of 1,3-diiodopropanes
Zinc powder (1.2 mmol) was added to a refluxing solution
of 1,3-diiodopropane (0.4 mmol) in EtOH (3 mL) under an
argon atmosphere. After 1–5 h at the same temperature, the
mixture was filtered through Celitew, then the solvent was
removed, and the residue was purified by preparative TLC
or column chromatography on silica gel.
4.3.1. 1,1-Dibenzylcyclopropane (7a). Colorless oil; IR
4.2.4. (2,2-Dimethylcyclopropyl)acetophenone (2g).
(neat) 3030, 2920, 1500, 1460, 1080, 1020, 760, 700 cmK1
;
Colorless oil; IR (neat) 2940, 1690, 750, 690 cmK1; H
1H NMR (400 MHz, CDCl3) dZ7.31–7.25 (4H, m), 7.24–
7.16 (6H, m), 2.56 (4H, s), 0.52 (4H, s); 13C NMR
(100 MHz, CDCl3) dZ140.1 (q), 129.5 (t), 128.0 (t), 126.0
(t), 41.5 (s), 20.8 (q), 10.7 (s); MS (FAB): m/z 222; HRMS
(EI) found: 222.1422 m/z, calcd for C17H18: MCZ
222.1409.
1
NMR (400 MHz, CDCl3) dZ7.96 (2H, m), 7.55 (1H, tt, JZ
7.4, 1.6 Hz), 7.46 (2H, m), 3.03 (1H, dd, JZ17.0, 7.0 Hz),
2.93 (1H, dd, JZ17.0, 7.2 Hz), 1.11 (3H, s), 1.06 (3H, s),
1.02–0.94 (1H, dddd, JZ8.7, 7.2, 7.0, 4.6 Hz), 0.56 (1H, dd,
JZ8.7, 4.6 Hz), 0.06 (1H, t, JZ4.6 Hz); 13C NMR

10144
D. Sakuma, H. Togo / Tetrahedron 61 (2005) 10138–10145
4.3.2. 1,1-Bis(p-methylbenzyl)cyclopropane (7b). Color-
(EI): m/z 194; HRMS (EI) found: 194.2046 m/z, calcd for
C14H26: MCZ194.2035.
1
less oil; IR (neat) 3000, 2920, 1520, 1020, 810 cmK1; H
NMR (400 MHz, CDCl3) dZ7.08 (8H, d, JZ1.7 Hz), 2.51
(4H, s), 2.33 (6H, s), 0.48 (4H, s); 13C NMR (100 MHz,
CDCl3) dZ137.0 (q), 135.3 (q), 129.4 (t), 128.7 (t), 41.1 (s),
21.0 (p), 20.9 (q), 10.6 (s); MS (FAB): m/z 250; HRMS (EI)
found: 250.1734 m/z, calcd for C19H22: MCZ250.1722.
4.3.9. 1-(20-(p-Methoxyphenyl)ethyl)-2-methylcyclopro-
pane (7k). Colorless oil; IR (neat) 2930, 1510, 1240,
1
1040, 820 cmK1; H NMR (400 MHz, CDCl3) syn form:
dZ7.10 (2H, d, JZ8.7 Hz), 6.82 (2H, d, JZ8.7 Hz), 3.78
(3H, s), 2.64 (2H, t, JZ7.7 Hz), 1.65–1.40 (2H, m), 1.01
(3H, d, JZ6.3 Hz), 0.82–0.65 (2H, m), 0.60 (1H, td, JZ8.4,
4.1 Hz), K0.31 (1H, td, JZ5.2, 4.1 Hz); anti form: dZ7.10
(2H, d, JZ8.7 Hz), 6.82 (2H, d, JZ8.7 Hz), 3.78 (3H, s),
2.62 (2H, m), 1.65K1.40 (2H, m), 0.99 (3H, d, JZ5.8 Hz),
0.45–0.33 (2H, m), 0.18 (1H, dt, JZ7.8, 4.6 Hz), 0.13 (1H,
dt, JZ7.8, 4.6 Hz); 13C NMR (100 MHz, CDCl3) dZ157.6
(q), 134.9 (q), 134.8 (q), 129.3 (t), 113.6 (t), 55.2 (p), 36.5
(s), 35.5 (s), 35.0 (s), 30.9 (s), 19.5 (t), 19.0 (p), 15.4 (t), 13.2
(p), 12.9 (s), 12.8 (t), 11.9 (s), 9.5 (t); MS (FAB): m/z 190;
HRMS (FAB) found: 190.1341 m/z, calcd for C13H18O:
MCHZ190.1358.
4.3.3. 1,1-Bis(p-methoxybenzyl)cyclopropane (7c). Color-
less oil; IR (neat) 2910, 2840, 1610, 1510, 1250, 1180, 1040,
1
820 cmK1; H NMR (400 MHz, CDCl3) dZ7.09 (4H, d,
JZ8.7 Hz), 6.83 (4H, d, JZ8.7 Hz), 3.80 (6H, s), 2.49 (4H,
s), 0.47 (4H, s); 13C NMR (100 MHz, CDCl3) dZ157.8 (q),
132.2 (q), 130.3 (t), 113.5 (t), 55.2 (p), 40.6 (s), 21.1 (q),
10.5 (s); MS (FAB): m/z 283; HRMS (FAB) found:
282.1620 m/z, calcd for C19H22O2: MCHZ282.1620.
4.3.4. 1,1-Bis(p-bromobenzyl)cyclopropane (7d). Color-
less oil; IR (neat) 2920, 1490, 1400, 1070, 1010, 800 cmK1
;
1H NMR (400 MHz, CDCl3) dZ7.40 (4H, d, JZ8.2 Hz),
7.02 (4H, d, JZ8.2 Hz), 2.47 (4H, s), 0.53 (4H, s); 13C
NMR (100 MHz, CDCl3) dZ138.8 (q), 131.2 (t), 131.1 (t),
119.9 (q), 40.8 (s), 20.5 (q), 10.8 (s); MS (FAB): m/z 379;
HRMS (FAB) found: 379.9577 m/z, calcd for C17H16Br2:
MCHZ379.9599.
Acknowledgements
Financial support from a Grant-in-Aid for Scientific
Research (16655012) by the Ministry of Education, Science,
Sports and Culture is gratefully acknowledged.
4.3.5. Diethyl cyclopropane-1,1-dicarboxylate (7e).
1
Colorless oil; IR (neat) 1730, 1320, 1210, 1140 cmK1; H
NMR (400 MHz, CDCl3) dZ4.20 (4H, q, JZ7.0 Hz), 1.43
(4H, s), 1.28 (6H, t, JZ7.0 Hz). This compound is available
from Aldrich.
References and notes
4.3.6. p-Bromobenzylcyclopropane (7f). Colorless oil; IR
1. Review: Donaldson, W. A. Tetrahedron 2001, 57, 8589 and
most of synthetic approach to cyclopropanes are cited therein.
2. (a) Doering, W. von E.; Hoffman, A. K. J. Am. Chem. Soc.
1954, 76, 6162. (b) Parham, W. E. Org. React. 1963, 13, 55. (c)
Dave, V.; Warnhoff, E. W. Org. React. 1970, 18, 217.
3. Doyle, M. P.; Forbes, D. C. Chem. Rev. 1998, 98, 911.
4. (a) Simmons, H. E.; Smith, R. D. J. Am. Chem. Soc. 1958, 80,
5323. (b) Simmons, H. E.; Smith, R. D. J. Am. Chem. Soc.
1959, 81, 4256. (c) Furukawa, J.; Kawabata, N.; Nishimura, J.
Tetrahedron 1968, 24, 53.
1
(neat) 3080, 3000, 1490, 1070, 1010, 820 cmK1; H NMR
(400 MHz, CDCl3) dZ7.40 (2H, d, JZ8.5 Hz), 7.13 (2H, d,
JZ8.5 Hz), 2.49 (2H, d, JZ7.0 Hz), 0.99–0.90 (1H, m),
0.52 (2H, ddd, JZ7.9, 5.7, 4.5 Hz), 0.18 (2H, dt, JZ5.7,
4.5 Hz); 13C NMR (100 MHz, CDCl3) dZ141.1 (q), 131.3
(t), 130.1 (t), 119.6 (q), 39.7 (s), 11.7 (t), 4.6 (s); MS (FAB):
m/z 210; HRMS (EI) found: 210.0049 m/z, calcd for
C10H11Br: MCZ210.0044.
4.3.7. Dodecylcyclopropane (7g). Colorless oil; IR (neat)
5. Phenyl(trihalomethyl)mercury with olefins: (a) Seyferth, D.;
Burlitch, J. M.; Heeren, J. K. J. Org. Chem. 1962, 27, 1491. (b)
Seyferth, D.; Minasz, R. J.; Treiber, A. J. H.; Burlitch, J. M.;
Dowed, S. R. J. Am. Chem. Soc. 1963, 28, 1163. Dialkyl-
halomethylaluminium with olefins: (c) Hoberg, H. Angew.
Chem. 1961, 73, 114. (d) Miller, D. B. Tetrahedron Lett. 1964,
989. Michael addition-initiated ring closure: (e) Bestmann,
H. J.; Seng, F. Angew. Chem. 1962, 74, 154. (f) Little, R. D.;
Dawson, J. R. Tetrahedron Lett. 1980, 21, 2609. (g) Artaud, I.;
Seyden-Penne, J.; Viout, P. Synthesis 1980, 34. (h)
Bhattacharjec, S. S.; Ila, H.; Junjappa, H. Synthesis 1982,
301. Isopropylidenetriphenylphosphorane with olefins: (i)
Krief, A.; Froidbise, A. Tetrahedron 2004, 60, 7637.
2920, 2850, 1460, 1020, 820, 720 cmK1 1H NMR
;
(400 MHz, CDCl3) dZ1.45–1.20 (20H, m), 1.19 (2H, dt,
JZ7.3, 7.0 Hz), 0.89 (3H, t, JZ6.9 Hz), 0.72–0.60 (1H, m),
0.39 (2H, ddd, JZ8.1, 5.5, 4.1 Hz), K0.01 (2H, dt, JZ5.5,
4.1 Hz); 13C NMR (100 MHz, CDCl3) dZ34.8 (s), 31.9 (s),
29.67 (s), 29.64 (s), 29.5 (s), 29.3 (s), 22.7 (s), 14.1 (p), 10.9
(t), 4.3 (s); MS (EI): m/z 210; HRMS (EI) found: 210.2361
m/z, calcd for C15H30: MCZ210.2348.
4.3.8. 10-Undecenylcyclopropane (7h). Colorless oil; IR
1
(neat) 2930, 2850, 1640, 1460, 1020, 910, 820 cmK1; H
NMR (400 MHz, CDCl3) dZ5.82 (1H, ddt, JZ17.2, 10.2,
6.8 Hz), 5.04–4.97 (1H, ddt, JZ17.2, 2.1, 1.7 Hz), 4.96–
4.91 (1H, ddt, JZ10.2, 2.1, 1.2 Hz), 2.05 (2H, m), 1.45–
1.22 (14H, m), 1.18 (2H, dt, JZ7.5, 7.0 Hz), 0.72–0.60 (1H,
m), 0.39 (2H, ddd, JZ8.2, 5.8, 4.0 Hz), K0.01 (2H, dt, JZ
5.8, 4.0 Hz); 13C NMR (100 MHz, CDCl3) dZ139.2 (t),
114.0 (s), 34.7 (s), 33.8 (s), 29.66 (s), 29.63 (s), 29.59 (s),
29.51 (s), 29.48 (s), 29.1 (s), 28.9 (s), 10.9 (t), 4.3 (s); MS
6. Nonhebel, D. C. Chem. Soc. Rev. 1993, 347.
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8. Baldwin, J. E. Chem. Commun. 1976, 134.
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´
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