Gold-catalyzed cyclization of 1-alkynyl cyclopropyl tert-butyl carbonate to construct multifunctionalized vinyl cyclopropane derivatives

Article abstract of DOI:10.1016/j.tet.2009.10.087

A convenient new method was developed to prepare two types of vinyl cyclopropane derivatives through gold-catalyzed cyclization of 1-alkynyl cyclopropyl tert-butyl carbonates 2. Different from the previous reported 5-exo-dig route, the 6-endo-dig addition

Full text of DOI:10.1016/j.tet.2009.10.087

Tetrahedron 66 (2010) 321–328
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Gold-catalyzed cyclization of 1-alkynyl cyclopropyl tert-butyl carbonate
to construct multifunctionalized vinyl cyclopropane derivatives
,
b
b
b,
*
Yu-Xin Zhang a, Lin Guo a , Ya-Hui Wang , Li-Li Zhu , Zili Chen
*
a School of Chemistry and Environment, Beijing University of Aeronautics and Astronautics, Beijing 100191, China
b Department of Chemistry, Renmin University of China, Beijing 100872, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 27 August 2009
Received in revised form 22 October 2009
Accepted 27 October 2009
Available online 29 October 2009
A convenient new method was developed to prepare two types of vinyl cyclopropane derivatives through
gold-catalyzed cyclization of 1-alkynyl cyclopropyl tert-butyl carbonates 2. Different from the previous
reported 5-exo-dig route, the 6-endo-dig addition is the preferred pathway to provide six-membered
cyclized carbonates. Two factors, including stereoelectronic effect and steric effect might affect the
regioselectivity. Therefore, low steric aliphatic substrates afforded only six-membered isomers. The
synthetic utility of compound 3 was also explored to afford a series of
derivatives.
b-carbonyl cyclopropanol
Keywords:
Vinyl cyclopropane
Cyclic carbonate
Gold-catalyzed reaction
6-endo-dig Process
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
reactions, we want to report herein a convenient new method to
prepare multifunctionalized vinyl cyclopropane derivatives via
gold-catalyzed cyclization of 1-alkynyl cyclopropyl tert-butyl
carbonates.
Vinyl cyclopropane species are found as the important struc-
tural elements in a wide range of bioactive natural, non-natural
compounds.1,2 With a unique combination of a reactive double
bond and an unstable three-membered ring in one molecule, these
species can be employed as C5 or C3 building blocks in many metal-
catalyzed inter- or intramolecular (5þ2,33þ2,4 4þ1)5 cycloaddition
reactions to construct cyclopentene or cycloheptene derivatives of
various structural characteristics and functionalities.6
In previous reports, most of the metal-catalyzed cyclization of
propargylic carbonates, as indicated in Scheme 1, are favored to
proceed in an intramolecular 5-exo-dig process to afford five-
membered ring products B.9 For example: Gagosz group has
reported that Au(I)-catalyzed 5-exo-dig cyclization of propargylic
tert-butyl carbonates to give five-membered 4-alkylidene-1,3-
dioxolan-2-ones even from an internal alkyne.10 Whereas in this
paper, gold-catalyzed reaction of 1-alkynyl cyclopropyl tert-butyl
carbonates 2 mainly provided six-membered isomers 3 (A type
products, Scheme 1) via a 6-endo-dig route. The unusual regio-
selectivity might be owing to the special stereoelectronic effect in
the cyclopropane-containing system.
Methods for the preparation of vinyl cyclopropane derivatives
are very limited. The reported results generally proceed via two
similar transformations, including addition of carbene to the con-
jugated diene7 or the reaction of
a-vinyl carbenoid with an isolated
olefin.8 However, the synthetic utilities of these transformations
often suffered from the tedious preparation of the diene or carbene
reactants, and from the difficulties to introduce structural or
functional diversity. Therefore, developing new approaches to
construct these important synthetic entities would greatly broaden
their application in organic synthesis.
O
R2
O
O
O
R2
R2
BocO
O
Favored
Disfavored
O
Gold (I) complexes have emerged as an efficient and mild cat-
alyst for the transformation of substrates possessing alkyne or al-
kene functionality into a range of useful structural motifs. As part of
a program directed toward the development of new gold-catalyzed
R1
R1
B
R1
A
Scheme 1. Metal-catalyzed cyclization of propargylic carbonates.
The starting 1-alkynyl cyclopropyl tert-butyl carbonate 2 can be
readily prepared from the reaction of 1-alkynyl cyclopropanol with
tert-butoxyl carbonate in CH2Cl2.11 Subsequent gold-catalyzed
* Corresponding authors. Tel./fax: þ86 10 6251 6660.
E-mail address: zilichen@ruc.edu.cn (Z. Chen).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.10.087

322
Y.-X. Zhang et al. / Tetrahedron 66 (2010) 321–328
cyclization of compound 2 afforded two types of vinyl cyclopropane
derivatives. The structure of the minor product 4a was identified to
be a five-membered spiro-cyclopropyl alkylidene-1,3-dioxolan-2-
one derivative by X-ray crystallography.12 The structure of 3a was
then determined to be a six-membered isomer.
A range of five- or six-membered carbonate bearing vinyl
cyclopropanes were then prepared. Synthetic utility of major
products 3 was also explored to provide cyclopropane-containing
b
-hydroxy ketone derivatives 5.13 These compounds represent
a useful source to prepare cyclopentanone and other elaborated
structures.14
2. Results and discussions
In the preliminary studies, the reaction of 1-phenyl alkynyl
cylcopropyl tert-butyl carbonate 2a was chosen as the model sys-
tem to investigate the reaction condition. As shown in Table 1,
when 0.5 mmol 2a was treated with 2 mol % equivalent of
AuPPh3Cl/AgBF4 in CH2Cl2 at rt for 50 h, two cyclized products 3a
and 4a were obtained in a total yield of 76% (3a/4a¼1.5/1).
Figure 1. The X-ray diffraction structure of compound 4a.
yields were lower than that in DCM (entries 6–8, Table 1). AuCl3 and
other non-gold catalysts, such as PtCl2, AgOTf, and Cu(OTf)2 were
then investigated. These catalysts were proved to be inferior to the
Au(I) complexes and afforded no product (entries 11–14, Table 1).
The optimal reaction condition was then determined to be 2 mol %
of AuPPh3Cl/AgOTf in CH2Cl2 at rt.
With the optimized condition in hand, we explored the scope
and the limitation of this reaction. As shown in Table 2, a range of 1-
alkynyl cyclopropyl tert-butyl carbonates were prepared through
the reaction of the corresponding 1-alkynyl cyclopropanols with
tert-butyl carbonate.
Table 1
Reaction optimization of gold-catalyzed cyclization of 1-phenyl ethynyl cyclopropyl
tert-butyl carbonate 2aa
O
O
O
O
catalyst
BocO
O
+
O
C2
C3
2a
3a
4a
Catalyst
T (h)
Sol/temp
Yield (%)b (ratio 3a/4a)c
Compound 2 were then treated with AuPPh3Cl/AgOTf to prepare
vinyl cyclopropane derivatives 3 and 4. Both aromatic and aliphatic
alkynyl substrates exhibited good reactivities. Two types of vinyl
cyclopropane derivatives were readily obtained in moderate to
good yields. Aryl alkynyl cyclopropyl tert-butyl carbonates bearing
electron-donating groups, such as methyl, ethyl, n-butyl, and
methoxy substitutes (Table 2, entries 2–5), displayed relative high
reactivities and gave higher conversion. While other aryl alkynyl
substrates with electron-withdrawing chloro or fluoro groups had
relative low reactivities (Table 2, entries 6–9). Aliphatic alkynyl
substrates also worked effectively in this reaction (Table 2, entries
10 and 11), which nevertheless, only gave the six-membered cy-
clization products.
The regioselectivity for the aromatic alkynyl substrates ranged
from 1.5/1 to 6/1. Electron rich substrates seem to have a better
selectivity for the formation of the major isomers (Table 2, entries 2–
5), as compared with the lower 3/4 ratio obtained in their electron
deficient counterparts (Table 2, entries 6–9). The highest ratio was
obtained in substrate 2g (Table 2, entry 5), which has an electron-
donating p-methoxy substitutes on the phenyl group. However, the
aliphatic substrates only gave the single major products.
1
2
3
4
5
6
7
8
AuPPh3Cl/AgBF4
AuPPh3Cl/AgSbF6
AuPPh3Cl/AgPF6
Au(PPh3)NTf2
AuPPh3Cl/AgOTf
AuPPh3Cl/AgOTf
AuPPh3Cl/AgOTf
AuPPh3Cl/AgOTf
AuPPh3Cl/AgOTf
AuPPh3Cl/AgOTf
AuCl3
50
15
48
72
2
DCM/rt
DCM/rt
DCM/rt
DCM/rt
DCM/rt
DCE/rt
76 (1.5/1)
65 (1.9/1)
0
11 (2.6/1)
88 (2.4/1)
78 (1.8/1)
60 (1.6/1)
50 (2.6/1)
0
Trace
0
0
0
0
2
40
38
40
20
30
48
48
48
THF/rt
Toluene/rt
CH3CN/rt
Et2O/rt
DCM/rt
DCM/rt
DCM/rt
DCM/rt
9
10
11
12
13
14
PtCl2
AgOTf
Cu(OTf)2
a
All reactions were carried out at 0.5 mmol scale, using 2 mol % of gold catalyst in
2 mL solvent at rt.
b
Separated yield.
The ratio 3a/4a was based on the separated yields.
c
The 1H and 13C NMR spectra data for compound 3a and 4a are
very similar. Only one obvious difference exists between the
chemical shift of 3a’s hydrogen at C2 position (5.52 ppm, 3a) and
that of 4a’s C3 hydrogen (5.15 ppm, 4a). The structure of 4a was then
identified to be 7-benzylidene-4,6-oxa-5-carbonyl-spiro[2,4]-hep-
tane by X-ray crystallography (Fig. 1). Then, the structure of 3a can
be deduced to be 7-phenyl-4,6-oxa-5-carbonyl-spiro[2,5]-7-octene.
A series of experiments were performed to optimize this
reaction. Different silver salts were tested, it was found that
AuPPh3Cl/AgPF6 and Au(PPh3)NTf2 have low activities (entries 3
and 4, Table 1). With AuPPh3Cl/AgPF6 as catalyst, the
desired product was obtained in 65% yield with 3a/4a¼1.9/1 (entry
2, Table 1). The best catalyst, as shown in Table 1, was proved to be
AuPPh3Cl/AgOTf (entry 5, Table 1), which provide 3a and 4a in 88%
with a ratio of 2.4/1. Several solvents were also screened. CH3CN
and Et2O were found to be ineffective (entries 9 and 10, Table 1).
When DCE, THF, and toluene were used as the solvent, the reaction
We assumed that the regioselectivity might be affected by two
factors. The first is the stereoelectronic effect. In substrate 2, angle
q
for C2–C1–O is larger than the normal bond angle in an sp3 hy-
bridized carbon (109.5ꢀ), because of the existence of a small,
strained bond angle in cyclopropane (Scheme 2). Therefore, SN2
addition of the carbonate oxygen onto the gold activated triple
bond is favored to proceed through a 6-endo-dig route (Scheme 2,
route a). However, high steric aromatic group would affect the
attack of the carbonyl oxygen, and favored the 5-exo-dig pathway to
construct minor five-membered isomer (Scheme 2, route b).
Aliphatic substrates, which have no high steric aromatic group,
would therefore give only the major products.
The quench step of the gold-catalyzed cyclization reaction was
then investigated (Scheme 3). When 3 equiv of D2O was added into

Y.-X. Zhang et al. / Tetrahedron 66 (2010) 321–328
323
Table 2
Gold-catalyzed cyclization of compound 2 to afford 3 and 4a
O
O
O
R
R
R
O
AuCl(PPh3)
O
t-Bu
O
R
HO
+
O
O
Boc-protection
AgOTf,
CH2Cl2, rt
O
1
2
3
4
Entry
1
Compound 2/yield (%)b
Products 3
Product 4
Yield (%)b (ratio a/b)c
O
O
O
O
84% (2.4/1)
85% (3/1)
O
BocO
O
2a
4a
3a
O
O
O
O
2
O
BocO
O
3b
2b
4b
O
O
O
O
3
4
87% (5/1)
O
BocO
O
2c
4c
3c
O
O
O
O
86% (2.3/1)
BocO
O
O
2d
3d
4d
O
O
O
O
O
O
O
5
6
7
8
81% (6/1)
O
BocO
O
3e
2e
4e
F
F
F
O
O
O
O
O
58% (1.6/1)
72% (1.6/1)
77% (2/1)
O
BocO
BocO
O
3f
4f
2f
O
O
O
Cl
F
Cl
F
Cl
F
O
O
2g
4g
3g
O
O
O
O
O
BocO
O
F
F
2h
F
4h
4i
3h
O
O
O
O
O
O
F
9
F
69% (1.5/1)
F
O
BocO
BocO
O
O
2i
3i
10
ND
80%
56%
2j
3j
O
O
11
ND
BocO
O
2k
3k
a
Unless noted, all reactions were carried out at 0.5 mmol scale, using 2 mol % of AuPPh3Cl/AgOTf in 2 mL CH2Cl2 at rt.
Separated yield.
The ratio 3/4 was based on the separated yields.
b
c

324
Y.-X. Zhang et al. / Tetrahedron 66 (2010) 321–328
As shown in Table 3, when enol carbonate 3b was treated with
a catalytic amount of p-toluene sulfonic acid in CH2Cl2 at rt, a new
compound, cyclopropane-containing -hydroxy ketone 5b, was
obtained in a high yield, in which the cyclic carbonate was re-
O
O
O
b
stereoelectronic effect
favored route
R
a
moved. Using the same method, five
were then synthesized (Table 3).
b-hydroxy ketone derivatives
Major
O
a
t-BuO
O
b
R
O
b
3. Conclusion
steric effect favored
route
O
O
R
In conclusion, we have developed a convenient new method
to prepare two types of vinyl cyclopropane derivatives through
gold-catalyzed cyclization of 1-alkynyl cyclopropyl tert-butyl
carbonates 2. Different from the previous results to give five-
minor
t-BuO
O
θ
R
3
membered products via
a 5-exo-dig route, cyclization of
O
2
compound 2 preferred to take a 6-endo-dig pathway to provide
six-membered carbonates. Two factors, including stereo-
electronic effect and steric effect might affect the regioselectivity.
Low steric aliphatic substrates afforded only six-membered vinyl
cyclopropane products. The synthetic utilities of compound 3
Scheme 2. A working mechanism for the regioselectivity.
the reaction mixture of compound 2a, it was found that 27% deu-
terium was incorporated into C2 position of compound 3a, and 36%
deuterium into C3 position of compound 4a.15
were also explored to afford a series of cyclopropyl
ketone derivatives.
b-hydroxy
4. Experimental section
F
F
F
t-Bu
O
AuCl(PPh3),
AgOTf,
O
O
4.1. Typical general procedure for the preparation of Boc-
protected cyclopropanol 2a
O
O
O
27% D
H(D)
O
O
+
O
CH2Cl2, rt,
3 eq. D2O
36% D
H(D)
2f
3f
4f
To a solution of 316 mg (2 mmol) of 1-alkynyl cyclopropanol 1
and 872 mg (4 mmol) di-tert-butyl-dicarbonate in 20 mL of
dichloromethane were added aqueous sodium hydroxide (2 N,
Scheme 3. Experiment to trap the reaction with D2O.
Table 3
Preparation of b
-hydroxy ketone derivatives 5a
O
O
R
HO
R
PTSA
CH2Cl2
O
O
5
3
3a
Product
Yield (%)b
O
O
HO
1
4
2
3
91
O
5b
O
3b
O
O
HO
85
88
O
5c
O
3c
O
O
HO
O
5d
O
3d
O
O
O
O
95
83
HO
O
5e
O
3e
O
O
HO
F
5
F
O
5i
O
3i
a
Unless noted, all reactions were carried out at 0.3 mmol scale, using a catalytic amount of p-toluene sulfonic acid in 2 mL CH2Cl2 at rt.
Separated yield.
b

Y.-X. Zhang et al. / Tetrahedron 66 (2010) 321–328
325
2 mL, 4 mmol), tetrabutylammonium chloride (138 mg, 0.5 mmol),
and then 4-dimethylaminopyridine (24.4 mg, 0.2 mmol) at 0 ꢀC.
After 30 min, the reaction mixture was extracted with dichloro-
methane. The combined organic phase was dried over MgSO4 and
concentrated with a rotary evaporator. The crude product was
purified via flash chromatography over silica gel with 50/1 PE/
EtOAc as eluting solvent. Compound 2a was then obtained in 62% as
a colorless liquid.
PE/AcOEt¼50/1). 1H NMR (400 MHz, CDCl3)
d
1.34 (s, 4H), 1.53 (s,
9H), 6.80–6.86 (m, 2H), 7.38–7.44 (m,1H).13C NMR (100 MHz, CDCl3)
d
16.5, 27.7, 50.3, 75.5, 83.1, 92.5, 104.2 (t, J¼25.2 Hz), 107.7, 111.4 (d,
J¼25.1 Hz), 134.5 (d, J¼9.5 Hz), 152.4, 161.7 (dd, J¼52.5, 12.2 Hz),
164.2 (dd, J¼55.0, 11.9 Hz). MS (m/z, rel intensity): 294 (Mþ, 2), 195
(14), 194 (100), 177 (82), 165 (53), 151 (32), 129 (25), 57 (77).
4.1.9. tert-Butyl 1-((3-fluorophenyl)ethynyl)cyclopropyl carbonate
2i. Obtained as colorless oil in 60% yield (Rf¼0.2, PE/AcOEt¼50/
4.1.1. tert-Butyl 1-(phenylethynyl)cyclopropyl carbonate2a. Obtained
as colorless oil in 62% yield (Rf¼0.2, PE/AcOEt¼50/1). 1H NMR
1). 1H NMR (400 MHz, CDCl3)
d 1.32 (s, 4H), 1.52 (s, 9H), 6.98–7.03
(m, 1H), 7.10–7.12 (m, 1H), 7.18–7.28 (m, 2H). 13C NMR (100 MHz,
CDCl3) 13C NMR (100 MHz, CDCl3)
16.4, 27.7, 50.2, 81.8, 83.0,
(400 MHz, CDCl3)
d
1.30 (s, 4H), 1.51 (s, 9H), 7.26–7.29 (m, 3H), 7.41–
d
7.43 (m, 2H). 13C NMR (100 MHz, CDCl3)
87.5, 122.6, 128.2, 128.3, 131.9, 152.5.
d
16.4, 27.7, 50.4, 82.9, 83.0,
88.5, 115.6 (d, J¼21.0 Hz), 118.5 (d, J¼22.7 Hz), 124.4 (d, J¼9.5 Hz),
127.6, 129.7 (d, J¼8.5 Hz), 152.5, 162.2 (d, J¼244.9 Hz). MS (m/z,
rel intensity): 276 (Mþ, 2), 176 (86), 159 (78), 147 (60), 133 (32),
57 (100).
4.1.2. tert-Butyl 1-((4-ethylphenyl)ethynyl)cyclopropyl carbonate
2b. Obtained as a yellow solid in 70% yield (Rf¼0.2, PE/AcOEt¼50/
1). 1H NMR (400 MHz, CDCl3)
d
1.21 (t, J¼7.6 Hz, 3H), 1.30 (s, 4H),
4.1.10. tert-Butyl 1-(hex-1-ynyl)cyclopropyl carbonate 2j. Obtained
as colorless oil in 78% yield (Rf¼0.2, PE/AcOEt¼50/1). 1H NMR
1.51 (s, 9H), 2.62 (q, J¼7.6 Hz, 2H), 7.13 (d, J¼8.0 Hz, 2H), 7.37 (d,
J¼8.4 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d
15.4, 16.4, 27.7, 28.8,
(400 MHz, CDCl3)
d
0.89 (t, J¼7.2 Hz, 3H), 1.13 (dd, J¼14.6, 3.6 Hz,
50.5, 82.8, 83.2, 86.7, 119.7, 127.7, 131.9, 144.8, 152.5. MS (m/z, rel
intensity): 286 (Mþ, 2), 187 (14), 186 (100), 171 (40), 169 (33), 157
(65), 129 (25), 57 (67).
4H), 1.36–1.49 (m, 13H), 2.20 (t, J¼6.8 Hz, 2H). 13C NMR (100 MHz,
CDCl3)
d 13.6, 15.8, 18.5, 21.8, 27.7, 30.5, 50.5, 78.2, 82.6, 84.0,
152.5. MS (m/z, rel intensity): 238 (Mþ, 1), 138 (18), 109 (22), 96
(20), 57 (100).
4.1.3. tert-Butyl 1-(p-tolylethynyl)cyclopropyl carbonate 2c. Obtained
as a yellow solid in 76% yield (Rf¼0.2, PE/AcOEt¼50/1). 1H NMR
4.1.11. tert-Butyl 1-(4-phenylbut-1-ynyl)cyclopropyl carbonate
(400 MHz, CDCl3)
d
1.23 (s, 4H),1.45–1.47 (m, 9H), 2.26 (s, 3H), 7.02–
2k. Obtained as colorless oil in 82% yield (Rf¼0.2, PE/AcOEt¼50/1).
7.04 (m, 2H), 7.24–7.28 (m, 2H). 13C NMR (100 MHz, CDCl3)
d
16.3,
1H NMR (400 MHz, CDCl3)
d 1.09–1.13 (m, 2H), 1.16–1.20 (m, 2H),
21.3, 27.3, 50.3, 83.0, 84.9, 86.7,119.5,128.9,131.7,138.3,146.7,152.4.
MS (m/z, rel intensity): 272 (Mþ, 2), 172 (75), 155 (49), 143 (65), 129
(38), 57 (100).
1.51 (s, 9H), 2.50 (t, J¼7.56 Hz, 2H), 2.82 (t, J¼7.56 Hz, 2H), 7.19–7.22
(m, 3H), 7.27–7.31 (m, 2H). 13C NMR (100 MHz, CDCl3)
d
15.9, 21.2,
27.7, 34.9, 50.3, 79.1, 82.6, 85.1, 126.2, 128.3, 128.5, 140.6, 152.6. MS
(m/z, rel intensity): 286 (Mþ, 2),186 (14),185 (29),157 (23),154 (14),
91 (65), 57 (100).
4.1.4. tert-Butyl 1-((4-butylphenyl)ethynyl)cyclopropyl carbonate
2d. Obtained as a yellow solid in 65% yield (Rf¼0.2, PE/AcOEt¼50/
1). 1H NMR (400 MHz, CDCl3)
d
0.90 (t, J¼7.6 Hz, 3H), 1.28–1.51
4.2. Typical procedure for the preparation of compounds 3
and 4
(m, 17H), 2.57 (t, J¼8.0 Hz, 2H), 7.08 (d, J¼8.0 Hz, 2H), 7.33 (d,
J¼8.4 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d 13.9, 16.4, 22.2, 27.7,
33.4, 35.5, 50.4, 82.8, 83.1, 86.7, 119.7, 128.3, 131.8, 143.4, 152.5. MS
(m/z, rel intensity): 314 (Mþ, 2), 215 (18), 214 (92), 171 (100), 142
(15), 57 (62).
To a solution of 30 mg compound 2a in 2 mL dichloromethane
was added 2% AuCl(PPh3)/AgOTf at rt. After stirred for 2 h under N2,
the reaction mixture was extracted with EtOAc. The organic phase
was combined, dried over MgSO4, and evaporated in vacuo. Crude
product purified by flash chromatography over silica gel gave the
desired cyclic carbonates 3a and 4a readily in 26% and 62% yields,
respectively.
4.1.5. tert-Butyl 1-((4-methoxyphenyl)ethynyl)cyclopropyl carbonate
2e. Obtained as a white solid in 71% yield (Rf¼0.2, PE/AcOEt¼50/1).
1H NMR (400 MHz, CDCl3)
d
1.28 (d, J¼1.6 Hz, 4H), 1.50 (s, 9H), 3.77
(s, 3H), 6.80 (d, J¼8.8 Hz, 2H), 7.36 (d, J¼8.8 Hz, 2H). 13C NMR
(100 MHz, CDCl3)
d
16.4, 27.7, 50.5, 55.2, 82.8, 82.9, 85.9, 113.8,
4.2.1. 7-Phenyl-4,6-oxa-5-carbonyl-spiro[2,5]-7-octene 3a. 1H NMR
114.6, 133.4, 152.5, 159.7.
(400 MHz, CDCl3)
d 0.97–1.01 (m, 2H),1.41–1.44 (m, 2H), 5.52 (s,1H),
7.39–741 (m, 3H), 7.58–7.61 (m, 2H). 13C NMR (100 MHz, CDCl3)
4.1.6. tert-Butyl 1-((4-fluorophenyl)ethynyl)cyclopropyl carbonate
d 14.38, 62.97,100.95,127.42,128.25,128.68,132.27,148.77. MS (m/z,
2f. Obtained as a white solid in 65% yield (Rf¼0.2, PE/AcOEt¼50/1).
rel intensity): 202 (Mþ,100),130 (38),129 (94),118 (78),102 (65), 90
(62). HRMS (EI) calcd for C12H10O3 [M]þ: 202.0630, found: 202.0625.
1H NMR (400 MHz, CDCl3)
d 1.17 (s, 4H), 1.37–1.39 (m, 9H), 6.86 (t,
J¼8.4 Hz, 2H), 7.25–7.29 (m, 2H). 13C NMR (100 MHz, CDCl3)
d 16.2,
27.5, 50.1, 81.8, 82.6, 87.1, 115.4 (d, J¼22.0 Hz), 118.5 (d, J¼3.5 Hz),
133.7 (d, J¼8.0 Hz), 152.4, 162.4 (d, J¼248.2 Hz). MS (m/z, rel in-
tensity): 276 (Mþ, 1), 176 (49), 159 (51), 147 (47), 133 (28), 57 (100).
4.2.2. 7-Benzylidene-4,6-oxa-5-carbonyl-spiro[2,4]-heptane 4a. IR
(neat) 1815, 1703, 1242, 1231, 1047, 1042, 918 cmꢁ1 1H NMR
.
(400 MHz, CDCl3)
d 1.20–1.25 (m, 2H), 1.64–1.68 (m, 2H), 5.15 (s,
1H), 7.24–7.26 (m, 1H), 7.35 (t, J¼7.2 Hz, 2H), 7.51 (d, J¼7.6 Hz, 2H).
4.1.7. tert-Butyl 1-((3-chlorophenyl)ethynyl)cyclopropyl carbonate
13C NMR (100 MHz, CDCl3)
d 14.40, 66.18, 97.63, 127.42, 128.25,
2g. Obtained as a white solid in 72% yield (Rf¼0.2, PE/AcOEt¼50/1).
128.68, 132.27, 151.62. MS (m/z, rel intensity): 202 (Mþ, 100), 130
(38), 129 (95), 118 (75), 115 (45), 102 (62), 90 (58), 89 (30). HRMS
(EI) calcd for C12H10O3 [M]þ: 202.0630, found: 202.0625.
1H NMR (400 MHz, CDCl3)
d 1.08 (s, 4H), 1.27–1.29 (m, 9H), 6.99–
7.07 (m, 3H), 7.15 (t, J¼1.6 Hz, 1H). 13C NMR (100 MHz, CDCl3)
d 16.3,
27.5, 49.9, 81.4, 82.6, 84.8, 124.2, 128.5, 131.4, 133.8, 152.3. MS (m/z,
rel intensity): 292 (Mþ, 2), 194 (13), 192 (35), 175 (38), 163 (28), 129
(21), 57 (100).
4.2.3. 7-(4-Ethylphenyl)-4,6-oxa-5-carbonyl-spiro[2,5]-7-octene
3b. 1H NMR (400 MHz, CDCl3)
d
0.98–1.01 (m, 2H), 1.26 (t, J¼7.6 Hz,
3H), 1.41–1.45 (m, 2H), 2.69 (q, J¼7.6 Hz, 2H), 5.50 (s, 1H), 7.25 (d,
4.1.8. tert-Butyl 1-((2,4-difluorophenyl)ethynyl)cyclopropyl carbon-
J¼8.4 Hz, 2H), 7.53 (d, J¼8.4 Hz, 2H). 13C NMR (100 MHz, CDCl3)
ate 2h. Obtained as
a
white solid in 85% yield (Rf¼0.2,
d 14.4, 15.4, 28.7, 62.9, 100.9, 124.2, 127.6, 128.2, 146.2, 147.1, 148.8.

326
Y.-X. Zhang et al. / Tetrahedron 66 (2010) 321–328
MS (m/z, rel intensity): 230 (Mþ, 52), 201 (98), 157 (48), 143 (42),
131 (52), 129 (88), 115 (37). HRMS (EI) calcd for C14H14O3 [M]þ:
230.0943, found: 230.0944.
151.6, 158.8. MS (m/z, rel intensity): 232 (Mþ, 89), 160 (40), 159 (86),
145 (100), 120 (48), 117 (63), 91 (42), 89 (48), 77 (41), 51 (37). HRMS
(EI) calcd for C13H12O4 [M]þ: 232.0736, found: 232.0738.
4.2.4. 7-(4-Ethylbenzylidene)-4,6-oxa-5-carbonyl-spiro[2,4]-heptane
4.2.11. 7-(4-Fluorophenyl)-4,6-oxa-5-carbonyl-spiro[2,5]-7-octene
4b. IR (neat) 3007, 2963, 2929, 2870, 1829, 1809, 1703, 1514, 1249,
3f. 1H NMR (400 MHz, CDCl3)
d 0.98–1.02 (m, 2H), 1.41–1.45 (m,
1229, 1194, 1045, 1015, 864, 760 cmꢁ1
.
1H NMR (400 MHz, CDCl3)
2H), 5.49 (s, 1H), 7.10 (t, J¼8.6 Hz, 2H), 7.57–7.61 (m, 2H). 13C NMR
d
1.21–1.28 (m, 5H), 1.65–1.69 (m, 2H), 2.66 (q, J¼7.6 Hz, 2H), 5.17 (s,
(100 MHz, CDCl3)
d
14.4, 62.9, 101.6, 115.8 (d, J¼21.5 Hz), 126.3 (d,
1H), 7.20 (d, J¼8.0 Hz, 2H), 7.46 (d, J¼8.0 Hz, 2H). 13C NMR
J¼8.3 Hz), 146.7, 147.8, 163.4 (d, J¼248.8 Hz). MS (m/z, rel intensity):
220 (Mþ, 95), 148 (45), 147 (100), 136 (94), 133 (48), 120 (74), 108
(95), 107 (39). HRMS (EI) calcd for C12H9O3F [M]þ: 220.0536, found:
220.0538.
(100 MHz, CDCl3)
d 14.3, 15.5, 28.6, 66.2, 97.6, 128.2, 128.3, 129.7,
143.7, 146.2, 151.6. MS (m/z, rel intensity): 230 (Mþ, 58), 201 (98),
157 (56), 143 (40), 131 (50), 129 (87), 115 (36). HRMS (EI) calcd for
C14H14O3 [M]þ: 230.0943, found: 230.0941.
4.2.12. 7-(4-Fluorobenzylidene)-4,6-oxa-5-carbonyl-spiro[2,4]-hep-
4.2.5. 7-(4-Methylphenyl)-4,6-oxa-5-carbonyl-spiro[2,5]-7-octene
tane 4f. IR (neat) 1834, 1815, 1703, 1591, 1508, 1366, 1252, 1231,
3c. 1H NMR (400 MHz, CDCl3)
d
0.97–1.01 (m, 2H), 1.41–1.44 (m,
1192, 1047, 1015, 864, 831 cmꢁ1. 1H NMR (400 MHz, CDCl3)
d
1.21–
1.25 (m, 2H), 1.67–1.71 (m, 2H), 5.15 (s, 1H), 7.06 (t, J¼8.8 Hz, 2H),
7.49–7.53 (m, 2H). 13C NMR (100 MHz, CDCl3)
14.4, 66.1, 96.6,115.6
2H), 2.40 (s, 3H), 5.49 (s, 1H), 7.22 (d, J¼8.2 Hz, 2H), 7.50 (d,
J¼8.2 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d
14.3, 21.3, 62.9, 100.9,
d
124.1, 127.4, 129.4, 139.9, 147.0, 148.8. MS (m/z, rel intensity): 216
(Mþ, 100), 201 (33), 143 (34), 132 (42), 129 (96), 115 (52), 104 (35).
HRMS (EI) calcd for C13H12O3 [M]þ: 216.0786, found: 216.0779.
(d, J¼21.5 Hz), 128.5, 129.9 (d, J¼7.5 Hz), 146.7, 151.3, 161.8 (d,
J¼246.4 Hz). MS (m/z, rel intensity): 220 (Mþ, 100), 148 (46), 147
(100), 136 (94), 133 (48), 120 (73), 108 (94), 107 (38). HRMS (EI)
calcd for C12H9O3F [M]þ: 220.0536, found: 220.0527.
4.2.6. 7-(4-Methylbenzylidene)-4,6-oxa-5-carbonyl-spiro[2,4]-hep-
tane 4c. IR (neat) 3456, 1809, 1703, 1694, 1514, 1362, 1249, 1229,
4.2.13. 7-(3-Chlorophenyl)-4,6-oxa-5-carbonyl-spiro[2,5]-7-octene
1194, 1047, 1020, 939, 864 cmꢁ1. 1H NMR (400 MHz, CDCl3)
d
1.20–
3g. 1H NMR (400 MHz, CDCl3)
d
1.01–1.05 (m, 2H), 1.44–1.48 (m,
1.24 (m, 2H), 1.65–1.69 (m, 2H), 2.37 (s, 3H), 5.15 (s, 1H), 7.17 (d,
2H), 5.59 (s, 1H), 7.35–7.37 (m, 2H), 7.48–7.51 (m, 1H), 7.60 (s, 1H).
J¼8.1 Hz, 2H), 7.43 (d, J¼8.1 Hz, 2H). 13C NMR (100 MHz, CDCl3)
13C NMR (100 MHz, CDCl3)
d 14.6, 62.9, 103.2, 122.3, 124.4, 129.7,
d
14.3, 21.3, 66.2, 97.6, 128.2, 129.4, 137.3, 146.2, 151.6. MS (m/z, rel
130.0,131.9,134.9, 146.4,147.3. MS (m/z, rel intensity): 236 (Mþ, 58),
201 (72), 152 (82), 136 (49), 129 (100), 124 (35), 89 (41). HRMS (EI)
calcd for C12H9O3Cl [M]þ: 236.0240, found: 236.0243.
intensity): 216 (Mþ, 93), 201 (31), 143 (35), 132 (44), 129 (100), 115
(55), 104 (38). HRMS (EI) calcd for C13H12O3 [M]þ: 216.0786, found:
216.0788.
4.2.14. 7-(3-Chlorobenzylidene)-4,6-oxa-5-carbonyl-spiro[2,4]-hep-
4.2.7. 7-(4-Butylphenyl)-4,6-oxa-5-carbonyl-spiro[2,5]-7-octene
tane 4g. IR (neat) 3447, 1815, 1638, 1629, 1595, 1049, 1015 cmꢁ1. 1H
3d. 1H NMR (400 MHz, CDCl3)
d
0.97–1.01 (m, 5H), 1.34–1.45 (m,
NMR (400 MHz, CDCl3) d 1.23–1.27 (m, 2H), 1.69–1.72 (m, 2H), 5.12
4H), 1.58–1.66 (m, 2H), 2.65 (t, J¼7.6 Hz, 2H), 5.50 (s, 1H), 7.23 (d,
(s, 1H), 7.22–7.31 (m, 2H), 7.40 (d, J¼7.6 Hz, 1H), 7.51 (s, 1H). 13C
J¼8.4 Hz, 2H), 7.52 (d, J¼8.4 Hz, 2H). 13C NMR (100 MHz, CDCl3)
NMR (100 MHz, CDCl3)
d 14.6, 66.2, 96.4, 126.3, 127.4, 128.0, 129.9,
d
13.9, 14.4, 22.3, 33.4, 35.5, 62.9, 100.9, 124.2, 127.6, 128.8, 144.9,
134.1, 134.5, 148.3, 151.1. MS (m/z, rel intensity): 236 (Mþ, 28), 201
(33), 154 (22), 152 (73), 136 (46), 129 (100), 124 (47), 89 (81), 63
(26), 39 (22). HRMS (EI) calcd for C12H9O3Cl [M]þ: 236.0240, found:
236.0243.
147.1, 148.8. MS (m/z, rel intensity): 258 (Mþ, 39), 202 (10), 201
(100),157 (32),143 (34),131 (47), 129 (52),115 (22). HRMS (EI) calcd
for C16H18O3 [M]þ: 258.1256, found: 258.1252.
4.2.8. 7-(4-Butylbenzylidene)-4,6-oxa-5-carbonyl-spiro[2,4]-heptane
4.2.15. 7-(2,4-Difluorophenyl)-4,6-oxa-5-carbonyl-spiro[2,5]-7-oc-
4d. IR (neat) 2957, 2926, 1829, 1809, 1701, 1249, 1229, 1194, 1047,
tene 3h. 1H NMR (400 MHz, CDCl3)
d
0.99–1.04 (m, 2H), 1.42–1.46
(m, 2H), 5.77 (s, 1H), 6.86–6.99 (m, 2H), 7.71–7.77 (m, 1H). 13C NMR
(100 MHz, CDCl3)
1020 cmꢁ1. 1H NMR (400 MHz, CDCl3)
d
0.94 (t, J¼7.4 Hz, 3H), 1.19–
1.23 (m, 2H), 1.33–1.39 (m, 2H), 1.56–1.68 (m, 4H), 2.61 (t, J¼7.6 Hz,
d
14.5, 62.8, 104.8 (t, J¼26.0 Hz), 107.4 (d,
2H), 5.15 (s, 1H), 7.17 (d, J¼8.2 Hz, 2H), 7.44 (d, J¼8.2 Hz, 2H). 13C
J¼14.8 Hz), 111.8 (dd, J¼21.3, 3.3 Hz), 128.1 (dd, J¼9.6, 3.1 Hz), 142.3
(d, J¼4.9 Hz), 146.6, 158.9 (d, J¼11.7 Hz), 161.6 (dd, J¼41.6, 12.2 Hz),
164.3 (d, J¼12.2 Hz). MS (m/z, rel intensity): 238 (Mþ, 50), 166 (28),
165 (58), 154 (94), 138 (62), 126 (100), 125 (26). HRMS (EI) calcd for
C12H8O3F2 [M]þ: 238.0442, found: 238.0420.
NMR (100 MHz, CDCl3)
d 13.9, 14.4, 22.4, 33.5, 35.4, 66.2, 97.6,
128.2, 128.8, 129.6, 142.4, 146.2, 151.6. MS (m/z, rel intensity): 258
(Mþ, 41), 202 (11), 201 (97), 157 (31), 143 (33), 131 (48), 129 (52),
115 (21). HRMS (EI) calcd for C16H18O3 [M]þ: 258.1256, found:
258.1251.
4.2.16. 7-(2,4-Difluorobenzylidene)-4,6-oxa-5-carbonyl-spiro[2,4]-
heptane 4h. IR (neat) 3447, 1811, 1695, 1611, 1587, 1501, 1429, 1359,
1242, 1221, 1144, 1049, 1020, 970 cmꢁ1. 1H NMR (400 MHz, CDCl3)
4.2.9. 7-(4-Methoxyphenyl)-4,6-oxa-5-carbonyl-spiro[2,5]-7-octene
3e. 1H NMR (400 MHz, CDCl3)
d 0.95–0.99 (m, 2H), 1.38–1.42 (m,
2H), 3.85 (s, 3H), 5.40 (s, 1H), 6.92 (d, J¼8.9 Hz, 2H), 7.53 (d,
d
1.26–1.30 (m, 2H), 1.69–1.74 (m, 2H), 5.38 (s, 1H), 6.80–6.85 (m,
1H), 6.91–6.96 (m, 1H), 7.89–7.95 (m, 1H). 13C NMR (100 MHz,
CDCl3)
J¼8.9 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d 14.3, 55.4, 63.0, 99.8,
114.1, 122.8, 125.8, 147.1, 148.6, 160.7. MS (m/z, rel intensity): 232
(Mþ, 100), 159 (50), 145 (65), 120 (24), 117 (30). HRMS (EI) calcd for
C13H12O4 [M]þ: 232.0736, found: 232.0727.
d
14.7, 66.4, 88.2 (d, J¼7.1 Hz), 103.7 (t, J¼25.6 Hz), 111.7 (dd,
J¼21.2, 3.7 Hz), 130.2 (dd, J¼9.3, 3.7 Hz), 148.2, 151.1, 158.1 (d,
J¼14.3 Hz), 160.5 (dd, J¼12.4, 7.4 Hz), 163.1 (d, J¼12.4 Hz). MS (m/z,
rel intensity): 238 (Mþ, 68), 166 (37), 165 (68), 154 (94), 138 (67),
126 (100), 125 (30). HRMS (EI) calcd for C12H8O3F2 [M]þ: 238.0442,
found: 238.0445.
4.2.10. 7-(4-Methoxybenzylidene)-4,6-oxa-5-carbonyl-spiro[2,4]-
heptane 4e. IR (neat) 3003, 2931, 2839, 1834, 1815, 1707, 1599, 1512,
1296, 1246, 1186, 1180, 1047, 1018, 843 cmꢁ1 1H NMR (400 MHz,
.
CDCl3)
d
1.18–1.23 (m, 2H), 1.63–1.67 (m, 2H), 3.84 (s, 3H), 5.13 (s,
4.2.17. 7-(3-Fluorophenyl)-4,6-oxa-5-carbonyl-spiro[2,5]-7-octene
1H), 6.90 (d, J¼8.8 Hz, 2H), 7.47 (d, J¼8.8 Hz, 2H). 13C NMR
3i. IR (neat) 1689, 1585, 1481, 1443, 1270, 1242, 1172, 1019 cmꢁ1. 1H
(100 MHz, CDCl3)
d
14.2, 55.3, 66.2, 97.3, 114.1, 124.9, 129.6, 145.2,
NMR (400 MHz, CDCl3) d 1.01–1.03 (m, 2H), 1.44–1.47 (m, 2H), 5.59

Y.-X. Zhang et al. / Tetrahedron 66 (2010) 321–328
327
(s, 1H), 6.93–6.97 (m, 1H), 7.25–7.36 (m, 3H). 13C NMR (100 MHz,
CDCl3)
123.0 (d, J¼2.3 Hz), 128.8, 130.0 (d, J¼8.2 Hz), 131.3 (d, J¼8.3 Hz),
147.8, 161.2 (d, J¼246.4 Hz). MS (m/z, rel intensity): 220 (Mþ, 100),
148 (28), 147 (56), 136 (65), 133 (24), 120 (39), 108 (44). HRMS (EI)
calcd for C12H9O3F [M]þ: 220.0536, found: 220.0534.
1182, 1008 cmꢁ1
.
1H NMR (400 MHz, CDCl3)
d
0.50–0.53 (m, 2H),
d
14.6, 62.9, 103.2, 112.3 (d, J¼21.2 Hz), 112.8 (d, J¼22.7 Hz),
0.93–0.97 (m, 5H), 1.35–1.41 (m, 2H), 1.59–1.66 (m, 2H), 2.69 (t,
J¼7.8 Hz, 2H), 3.25 (s, 2H), 4.03 (s, 1H), 7.29 (d, J¼8.2 Hz, 2H), 7.88
(d, J¼8.2 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d 12.9, 13.9, 22.3, 33.2,
35.7, 45.8, 52.2, 128.2, 128.8, 134.3, 149.5, 200.6. MS (m/z, rel in-
tensity): 232 (Mþ, 5), 203 (7), 176 (8), 162 (10), 161 (100), 133 (18),
91 (8). HRMS (EI) calcd for C15H20O2 [M]þ: 232.1463, found:
232.1466.
4.2.18. 7-(3-Fluorobenzylidene)-4,6-oxa-5-carbonyl-spiro[2,4]-hep-
tane 4i. IR (neat) 3447, 2924, 1815, 1749, 1692, 1610, 1587, 1442,
1280, 1244, 1197, 1152, 1049, 1024 cmꢁ1. 1H NMR (400 MHz, CDCl3)
4.3.4. 2-(1-Hydroxycyclopropyl)-1-(4-methoxyphenyl)ethanone
d
1.21–1.25 (m, 2H), 1.67–1.70 (m, 2H), 5.13 (s, 1H), 6.92–6.96 (m,
5e. IR (neat) 3466, 1665, 1601, 1574, 1510, 1261, 1219, 1171, 1113,
1H), 7.23–7.33 (m, 3H). 13C NMR (100 MHz, CDCl3)
d
14.6, 66.2, 96.6,
1015 cmꢁ1 1H NMR (400 MHz, CDCl3)
. d 0.47–0.50 (m, 2H), 0.90–
114.3 (d, J¼21.2 Hz), 114.8 (d, J¼22.8 Hz), 124.0 (d, J¼2.3 Hz), 130.1
(d, J¼8.3 Hz), 134.3 (d, J¼8.3 Hz), 148.2, 151.1, 162.9 (d, J¼244.0 Hz).
MS (m/z, rel intensity): 220 (Mþ, 100), 148 (25), 147 (52), 136 (65),
133 (27), 120 (38), 108 (45). HRMS (EI) calcd for C12H9O3F [M]þ:
220.0536, found: 220.0532.
0.92 (m, 2H), 3.20 (s, 2H), 3.87 (s, 3H), 6.94 (d, J¼8.8 Hz, 2H), 7.91 (d,
J¼8.8 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d 12.9, 45.5, 52.3, 55.5,
113.9, 129.7, 130.4, 163.9, 199.4. MS (m/z, rel intensity): 206 (Mþ, 2),
177 (10), 150 (9), 135 (100), 133 (10), 107 (7), 77 (8). HRMS (EI) calcd
for C15H20O2 [M]þ: 206.0943, found: 206.0944.
4.2.19. 7-Butyl-4,6-oxa-5-carbonyl-spiro[2,5]-7-octene 3j. IR (neat)
4.3.5. 1-(3-Fluorophenyl)-2-(1-hydroxycyclopropyl)ethanone 5i. IR
3466, 2959, 2931, 2872,1782,1713,1265, 1184, 1136,1103, 1047, 966,
(neat) 3447, 1680, 1587, 1487, 1445, 1269, 1246, 1192, 1169,
941 cmꢁ1
.
1H NMR (400 MHz, CDCl3)
d
0.79–0.81 (m, 2H), 0.91 (t,
1153 cmꢁ1. 1H NMR (400 MHz, CDCl3)
d 0.49–0.52 (m, 2H), 0.91–
J¼7.3 Hz, 3H) 1.24–1.28 (m, 2H), 1.31–1.40 (m, 2H), 1.48–1.55 (m,
0.94 (m, 2H), 2.42 (s, 3H), 3.22 (s, 2H), 3.81 (s, 1H), 7.26–7.31 (m,
2H), 2.18 (t, J¼7.4 Hz, 2H), 4.77 (s, 1H). 13C NMR (100 MHz, CDCl3)
1H), 7.43–7.48 (m, 1H), 7.62 (d, J¼9.2 Hz, 1H), 7.70 (d, J¼7.7 Hz,
d
13.7, 21.9, 27.8, 31.3, 62.5, 101.7,147.3, 151.9. MS (m/z, rel intensity):
1H). 13C NMR (100 MHz, CDCl3)
d 12.9, 46.4, 52.0, 114.7 (d,
182 (Mþ, 40), 85 (100), 81 (17), 57 (51), 56 (26), 41 (16). HRMS (EI)
calcd for C10H14O3 [M]þ: 182.0943, found: 182.0942.
J¼22.2 Hz), 120.6 (d, J¼21.3 Hz), 123.8 (d, J¼2.7 Hz), 130.4 (d,
J¼7.5 Hz), 138.6 (d, J¼5.9 Hz), 162.9 (d, J¼246.9 Hz), 199.4. MS
(m/z, rel intensity): 194 (Mþ, 2), 166 (7), 165 (10), 138 (18), 123
(100), 96 (10), 95 (33). HRMS (EI) calcd for C11H11O2F [M]þ:
194.0743, found: 194.0744.
4.2.20. 7-Phenethyl-4,6-oxa-5-carbonyl-spiro[2,5]-7-octene 3k. IR
(neat) 3501, 3026, 2929, 1778, 1715, 1603, 1497, 1454, 1373, 1261,
1186, 1128, 1053, 1029 cmꢁ1. 1H NMR (400 MHz, CDCl3)
d 0.79–0.81
(m, 2H), 1.27–1.29 (m, 2H), 2.53 (t, J¼8.1 Hz, 2H), 2.90 (t, J¼8.1 Hz,
Acknowledgements
2H), 4.76 (s, 1H), 7.20–7.26 (m, 3H), 7.28–7.35 (m, 2H). 13C NMR
(100 MHz, CDCl3)
d 13.7, 32.1, 33.6, 62.5, 102.8, 126.4, 128.4, 128.6,
Financial support from Renmin University of China and National
Science Foundation of China (Nos. 20502033) is greatly appreciated.
140.1, 147.2, 150.7. MS (m/z, rel intensity): 230 (Mþ,19),186 (12), 105
(44), 91 (100). HRMS (EI) calcd for C14H14O3 [M]þ: 230.0943, found:
230.0944.
Supplementary data
4.3. Typical procedure for the preparation of compound 5
Experimental details and NMR spectra are available as Supple-
mentary data. Supplementary data associated with this article can
be found in online version, at doi:10.1016/j.tet.2009.10.087.
To a solution of 20 mg compound 3d in 5 mL dichloromethane
was added 1 mg p-toluene sulfonic acid at rt. After stirring for 3 h,
the organic solvent was evaporated in vacuo. The combined organic
phase purified by flash chromatography on silica gel gave the de-
sired products 5d in 91% yields.
References and notes
1. (a) The Chemistry of the Cyclopropyl Group; Patai, S., Rappoport, Z., Eds.; Wiley:
Chichester, UK, New York, NY, Brisbane, Toronto, Singapore, 1987; (b) Small ring
compounds in organic synthesis I–IV. In Topics in Current Chemistry; de Meijere,
A., Ed.; Springer: Berlin, 1986; p 133; 1987, 135; 1988, 144; 1990, 155; (c) Wong,
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4.3.1. 1-(4-Ethylphenyl)-2-(1-hydroxycyclopropyl)ethanone 5b. IR
(neat) 3447, 2967, 2934, 1672, 1607, 1460, 1414, 1373, 1285, 1267,
1240, 1219, 1182, 1009 cmꢁ1. 1H NMR (400 MHz, CDCl3)
d 0.50–0.53
(m, 2H), 0.93–0.96 (m, 2H), 1.28 (t, J¼7.6 Hz, 3H), 2.73 (q, J¼7.6 Hz,
2H), 3.26 (s, 2H), 4.02 (s, 1H), 7.32 (d, J¼8.2 Hz, 2H), 7.89 (d,
J¼8.2 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d 12.9, 15.2, 28.9, 45.9,
52.2, 128.2, 131.7, 134.3, 150.7, 200.6. MS (m/z, rel intensity): 204
(Mþ, 2), 175 (8), 148 (7), 134 (8), 133 (100), 105 (10). HRMS (EI) calcd
for C13H16O2 [M]þ: 204.1150, found: 204.1151.
4.3.2. 2-(1-Hydroxycyclopropyl)-1-p-tolylethanone 5c. IR (neat)
3447, 1672, 1607, 1285, 1221, 1207, 1182, 1011 cmꢁ1 1H NMR
.
(400 MHz, CDCl3)
d 0.48–0.51 (m, 2H), 0.91–0.94 (m, 2H), 2.42 (s,
3H), 3.23 (s, 2H), 3.99 (s, 1H), 7.27 (d, J¼8.2 Hz, 2H), 7.84 (d,
J¼8.2 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d 12.9, 21.7, 45.8, 52.2,
128.2, 129.4, 134.1, 144.6, 200.5. MS (m/z, rel intensity): 190 (Mþ, 3),
161 (9), 134 (10), 119 (100), 91 (23). HRMS (EI) calcd for C12H14O2
[M]þ: 190.0994, found: 190.0995.
4.3.3. 1-(4-Butylphenyl)-2-(1-hydroxycyclopropyl)ethanone 5d. IR
(neat) 3502, 3005, 2957, 2929, 2860, 1672, 1606, 1462, 1413, 1219,

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