Highly regioselective tandem formal substitution and decarboxylation of 2-acyl-1-chlorocyclopropanecarboxylates with sodium sulfinates

Article abstract of DOI:10.1016/j.tet.2016.04.062

This article reported a highly regioselective tandem formal nucleophilic substitution and decarboxylation reaction of alkyl 2-acyl-1-chlorocyclopropanecarboxylates with sodium sulfinates under basic conditions. Actually, alkyl 2-acyl-1-chlorocyclopropanec

Full text of DOI:10.1016/j.tet.2016.04.062

Tetrahedron 72 (2016) 3436e3442
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Highly regioselective tandem formal substitution and
decarboxylation of 2-acyl-1-chlorocyclopropanecarboxylates with
sodium sulfinates
*
Yuequan Zhu, Yuefa Gong
School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
This article reported a highly regioselective tandem formal nucleophilic substitution and decarboxylation
reaction of alkyl 2-acyl-1-chlorocyclopropanecarboxylates with sodium sulfinates under basic condi-
tions. Actually, alkyl 2-acyl-1-chlorocyclopropanecarboxylates could be easily converted into cyclo-
propene intermediates by simple 1,2-elimination of hydrogen chloride, and this highly reactive
cyclopropene quickly combines with sodium sulfinate via a regioselective 1,4-Michael addition. Sub-
sequent esterolysis and decarboxylation of the 1,4-Michael adducts afforded 1-aroylsulfonyl-2-
aroylcyclopropanes in high yields. This observation firstly demonstrates that direct Michael addition of
sodium sulfinates with reactive cyclopropene is really workable.
Received 19 February 2016
Received in revised form 21 April 2016
Accepted 22 April 2016
Available online 25 April 2016
Keywords:
Tandem reaction
Decarboxylation
Sodium sulfinate
Cyclopropene
Ó 2016 Elsevier Ltd. All rights reserved.
1. Introduction
A: our previous work
-
HF2- or H2F3
Cl
F
base
R1
R1
R1
Cyclopropenes, for their unique reactivity that extends far be-
yond chemical properties typical for common alkenes, has attrac-
ted increasing attention of chemists in the past decades.1 Recently,
a more reactive cyclopropene intermediate I (Scheme 1A) bearing
two electron-withdrawing groups on its C]C bond was observed
during our investigation in the formal fluorination reaction of ethyl
2-aroyl-1-chlorocyclopropanecarboxylates with HFꢀ2 or H2F3ꢀ.2 To
our knowledge, this is one successful example for unique nucleo-
philic addition reaction of hydrogen fluoride with electro-deficient
alkenes under weakly basic conditions.
Inspired by this observation, we want to evaluate nucleophilic
addition reactions of other typical weak nucleophiles with the
electron-deficient cyclopropenes generated in situ. Among them,
sodium sulfinates as a kind of weaker nucleophile, to date, are
rarely reported in direct Michael addition reaction with electron-
deficient alkenes except with some special olefines such as alke-
nyliodonium salt (Scheme 1B).3 For the wide applications of
cyclopropyl sulfones in synthesis4e8 and potential antimicrobial
and pesticidal activities,9 our attention was focused on the possi-
bility to prepare cyclopropyl sulfones through direct Thia-Michael
COOR2
COOR2
COOR2
O
O
O
I
B: previous work
O
R
X
R
+
Ar
S
IPh
BF4
ONa
ArSO2
X
X=F, Cl, Br
C: proposed reaction in this work
Cl
SO2Ar
base
ArSO2Na
R1
R1
R1
COOR2
COOR2
COOR2
O
O
O
I
Scheme 1. The additive reactions of weak nucleophiles with alkenes.
addition of sodium sulfinates with the reactive electron-deficient
cyclopropenes (Scheme 1C).
In general, cyclopropyl sulfones could be prepared from the
cycloaddition of vinylic sulfones with active methylene com-
pounds,10 cyclization of sulfone-stabilized carbanions and electron-
deficient alkenes,11 or cycloisomerization of terminal epoxides with
sodium salts of diethyl (phenylsulfonyl)-methylphosphonate.12
Moreover, they could also be formed from further oxidation of
* Corresponding author. Tel.: þ86 027 87543232; fax: þ86 027 87543632; e-mail
address: gongyf@mail.hust.edu.cn (Y. Gong).
http://dx.doi.org/10.1016/j.tet.2016.04.062
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.

Y. Zhu, Y. Gong / Tetrahedron 72 (2016) 3436e3442
3437
cyclopropyl sulfides.13 There is still a great demand for a general
Table 1
Optimization of reaction conditionsa
and convenient procedure from readily available starting materials.
Based on the above idea and current research situation, we
have tried the possible reaction between 2-aroyl-1-
chlorocyclopropanecarboxylates and sodium sulfinates. As a con-
sequence, a highly regioselective tandem reaction involving 1,2-
elimination of HCl, 1,4-Michael addition of arylsulfinate, ester-
olysis and decarboxylation occurred smoothly, affording a variety
of cyclopropyl sulfones in high yields with dr>20:1. In fact, it was
the first instance reported hitherto about direct Michael addition
of sodium arylsulfinate with cyclopropene intermediate I. More-
over, the introduction of sulfonyl group makes the subsequent
esterolysis and decarboxylation proceed more easily in a tandem
process.
Entry Base
Solvent
Time (h)b Conversion (%) Yield(%)c
3aa
4aa
1
K2CO3
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
24
24
10
2
5
4
3
0.5
24
24
2
62
40
62(38) 16(10)
64(26) 12(5)
19
d
2
3
4
5
Na2CO3
K3PO4
Cs2CO3
NaOH
KOH
100
100
100
100
100
100
26
70
89
48
48
33
26
d
10
4
16
d
6
7
CH3ONa DMSO
8
9
t-BuOK
DIPEA
TEA
DMSO
DMSO
DMSO
DMSO
DMF
CH3CN
1,4-Dioxane 24
1,2-DCE
Toluene
DMSO
27(7)
51(22)
16
11
4
10
11
12
13
14
15
16
17d
18e
44
d
DBU
100
100
100
100
46
30
100
100
43
74
37
15
43(20)
38(11)
81
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
4
4
2. Results and discussion
17
d
24
24
10
24
d
Initially, we began our study choosing ethyl 2-benzoyl-1-
chlorocyclopropanecarboxylate 1a and sodium benzenesulfinate
2a as benchmark substrates. Fortunately, the product 4aa in 74%
yield with dr>20:1 was observed in the presence of 1 equiv Cs2CO3
in DMSO at 80 ꢁC (Scheme 2). The structure of product for this
process was carefully characterized by 1H and 13C NMR spectros-
copy and HRMS, and the major isomer was assigned to be trans-4aa.
This assignment was further supported by single crystal X-ray
analysis of product 4bd (see Supplementary data). It should be
mentioned that product 3aa (in 18% yield) yielded through simple
sulfonate addition, which was hardly separated from 4aa by silica
gel column chromatography.
9
34
DMSO
5
a
Unless otherwise noted, the reaction was performed with 1a (0.2 mmol), 2a
(0.4 mmol), and the indicated base in solvent at 80 ꢁC.
b
Determined by TLC.
Yields based on converted 1a, and isolated yields in parentheses.
Cs2CO3 (0.3 mmol).
Reaction was performed at room temperature.
c
d
e
formation of 4aa in relatively low yields (Table 1, entries 17e18).
Based on the above observations, the optimized reaction conditions
chosen for further investigation were as follows: substrate
(1 equiv), sodium sulfinate (2 equiv), Cs2CO3 (2 equiv) in DMSO at
80 ꢁC (Table 1, entry 4).
Under the optimized conditions, the reactions of sodium ben-
zenesulfinate 2a with
a
variety of alkyl 2-acyl-1-
chlorocyclopropanecarboxylates 1ae1o were studied. All the ob-
served results were summarized in Table 2. In all the cases, the
corresponding products 4bae4ka were respectively produced with
excellent diastereoselectivities (dr up to 20:1). In contrast, the
product yields obviously varied with the change of R1 groups for 1,
though the effect of their electronic property seems to be irregular
(entries 1e10). For example, both 1b with electron-donating 4-Me
group and 1d with electron-withdrawing 4-Cl group gave the
corresponding products 4ba and 4da in excellent yields, whereas
1c with 4-MeO group and 1e with 4-Br group provided moderate
yields of 4ca and 4ea. Among them, the lowest yield was observed
in the case of 1g with a 4-Ph group (entry 7). In addition, substrates
1he1k with 2-furyl, 2-thienyl, 1-naphthyl or 1-pyrenyl groups
were also tolerated in this process, affording almost the corre-
sponding products 4gae4ka in moderate yields with high dr values
(up to 20:1), respectively (Table 2, entries 8e11). Moreover, it
should be noted that the electronic property of R1 groups of 1 has
an obvious influence on the reaction rates, and the electron-
donating group decelerated the reaction. By the way, the steric
effect of R2 group on this reaction was also examined under the
same conditions. According to the results listed in Table 2 (entries
12e15), we realized that the steric hindrance had a little influence
on this cascade process. In fact, both small methyl ester 1l and the
bulky t-butyl ester 1m gave the product 4aa in highest yields in
89%, 87% with excellent dr value (entries 13e14). When R2 is
a functional group like (CH2)2Cl or benzyl, substrates 1n or 1o were
also adapted to the reaction, furnishing the expected product 4aa in
high yields (Table 2, entries 15e16).
Scheme 2. Formal substitution reaction of 1a with sodium sulfinate 2a.
In order to get the optimal reaction conditions, several param-
eters including base, solvent and reaction temperature were
screened using the above reaction of 1a with 2a as the model. The
observed results are summarized in Table 1. Firstly, a variety of
inorganic and organic bases were assessed. From the results listed
in Table 1 (entries 2e11), we can conclude all of the inorganic bases
can promote this reaction, but their property has a great influence
on the reaction. Common bases like K2CO3 or Na2CO3 showed in-
ferior catalytic activity, and gave only low conversions after 24 h
(Table 1, entries 1e2). Strong base was conducive to the further
decarboxylation of this reaction process. Among all the inorganic
bases such as K3PO4, NaOH, KOH, and CH3ONa, Cs2CO3 was the most
suitable one, and the product 4aa was produced in 89% yield with
dr>20:1 possibly owing to its high solubility in DMSO (Table 1,
entries 3e7). In contrast, strong base t-BuOK obviously accelerated
the consumption rate of 1a, but led to a significant decline in the
yield of 4aa (Table 1, entry 8). This decline could be attributed to
much faster 1,2-elimination of 1a and subsequent polymerization
of the cyclopropene intermediate generated in situ under the
strongly basic conditions. On the other hand, organic bases such as
DIPEA, TEA and DBU also can promote the reaction, but the product
yields were unsatisfied (Table 1, entries 9e11).Then, some com-
monly used solvents were screened. Strong polar aprotic solvents
such as DMSO, DMF seems to be good choice for the high yields of
4aa (Table 1, entries 4, 12e16). We realized that the solubility of
base has a marked influence on the reaction in solvents, and DMSO
was the most appropriate one. Decreasing the loading of base to
1.5 equiv or lowering reaction temperature resulted in the
Next, we examined the reaction of 2-benzoyl-1-
chlorocyclopropaneformate 1a with a group of sodium sulfinates.
And the results were summarized in Table 3. The introduction of
electronically different substituents such as Me, OMe and Cl groups

3438
Y. Zhu, Y. Gong / Tetrahedron 72 (2016) 3436e3442
Table 2
Substrate scope for the reaction of 1 with 2aaa
O
Cl
S
Cs2CO3
R1
R1
O
ONa
+
O
S
DMSO, 80oC
COOR2
O
O
1a-1o
2a
4
Entry
1
R1
R2
Time (h)b (h)b
Product
Yield (%)c
drd
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
C6H5
Et
Et
Et
Et
Et
Et
Et
Et
2
6
8
2
2
2
3
2
5
6
4
2
8
4
2
4aa
4ba
4ca
4da
4ea
4fa
4ga
4ha
4ia
89
80
68
88
60
48
33
78
70
55
72
89
87
79
73
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
4-MeC6H4
4-MeOC6H4
4-ClC6H4
4-BrC6H4
2-BrC6H4
4-PhC6H4
2-Furyl
2-Thienyl
1-Naphthyl
1-Pyrenyl
C6H5
9
Et
Et
10
11
12
13
14
15
4ja
Me
Me
t-Bu
(CH2)2Cl
Benzyl
4ka
4aa
4aa
4aa
4aa
C6H5
C6H5
C6H5
a
Reaction conditions: 1 (0.2 mmol), 2a (0.4 mmol) and Cs2CO3 (0.4 mmol) in DMSO (2 mL) was stirred at 80 ꢁC.
Determined by TLC.
b
c
Isolated by column chromatography.
d
Diastereomeric ratios (trans:cis) determined by 1H NMR of the crude product.
on the para position of benzene ring of sodium benzenesulfinate
reaction rate and the product yields was also observed in these
cases (Table 3, entries 8e13).
caused a marked decrease in the yields of the expected products
4ab, 4ac and 4ad, despite of the high dr values (Table 3, entries
2e4). Sodium thiophene-2-sulfinate 2e can also take reaction with
1a smoothly to give the expected product 4ae in 68% yield with
dr>20:1 (Table 3, entry 5). In the case of sodium methanesulfinate
2f, the reaction also underwent smoothly and afforded the formal
substitution product 3af with high dr value (Table 3, entry 6) rather
than the desired decarboxylation product, indicative that the
property of sulfonyl group has a big influence on the subsequent
esterolysis. Sodium trifluoromethanesulfinate 2g, a much weaker
nucleophile, did not react with 1a under the same conditions (Table
3, entry 7). Similar substituent effect of R1 group of 1 on the
In order to further investigate the tandem process, we con-
ducted some control experiments shown in Scheme 3. First, we
found that only the formal substitution product 3aa was generated
and isolated in 83% yield when the reaction of 1a and 2a was per-
formed in the presence of 1.5 equiv Cs2CO3 at room temperature
(Scheme 3,a). When the isolated product 3aa was treated with
1 equiv Cs2CO3 in DMSO at 80 ꢁC, it was readily converted into 4aa
in 88% yield with dr>20:1 (Scheme 3,b). In this case, the total yield
for 4aa is 70%. When the crude product 3aa was further treated
with additional 1 equiv of Cs2CO3 in DMSO at 80 ꢁC without iso-
lation, the desired decarboxylation product 4aa was obtained in
total 66% yield (Scheme 3c). Compared with the 89% yield (Table 2,
entry1), the relatively lower yields imply that the simultaneous
esterolysis and decarboxylation would benefit the formal sub-
stitution reaction to some extent. In addition, the existence of
arylsulfonyl group made the esterolysis and decarboxylation of 3aa
proceed more easily in basic media.
Table 3
Substrate scope for the reaction of 1 with 2a
Cl
O
S
Cs2CO3
R1
R1
+
O
R3
S
O
R3
ONa
DMSO, 80oC
COOEt
O
O
1
2
4
Entry
1
2
Time (h)b Product Yield (%)c drd
O
O
S
1a 2a(R3¼C6H5)
2
9
7
9
6
24
24
12
12
4aa
4ab
4ac
4ad
4ae
3af
89
50
66
51
68
53
d
>20:1
Cl
1
COOEt
1.5 equiv. Cs2CO3
DMSO, rt
(a) Ph
+
2
1a 2b(R3¼4-MeC6H4)
1a 2c(R3¼4-OMeC6H4)
1a 2d(R3¼4-ClC6H4)
1a 2e(R3¼2-thienyl)
1a 2f(R3¼Me)
1a 2g(R3¼CF3)
1b 2b
>20:1
>20:1
>20:1
>20:1
>20:1
d
Ph
Ph
ONa
COOEt
S
O
3e
4
O
O
Ph
1a
2a
3aa
5e
6
yield 83%, dr>20:1
O
O
COOEt
7
8
9
10
11
12e
13e
NR
1 equiv. Cs2CO3
DMSO, 80oC
(b)
Ph
Ph
4bb
4bd
4db
4dd
4ib
4id
51
33
63
43
51
19
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
O
S
S
O
Ph
1b 2d
1d 2b
1d 2d
1i
1i
Ph
O
O
4aa
3aa
5.5
yield 88%, dr>20:1
6
12
12
O
O
2b
2d
Cl
COOEt
1) 1.5 equiv. Cs2CO3
DMSO, rt
(c)
Ph
+
S
Ph
Ph
ONa
O
S
a
2) 1 equiv. Cs2CO3
DMSO, 80oC
Reaction conditions: 1 (0.2 mmol), 2a (0.4 mmol) and Cs2CO3 (0.4 mmol) in
O
Ph
O
DMSO (2 mL) was stirred at 80 ꢁC.
2a
1a
4aa
b
Determined by TLC.
overyield 66%, dr>20:1
c
Isolated by column chromatography.
d
Diastereomeric ratios (trans:cis) determined by 1H NMR of the crude product.
Scheme 3. Some control experiments.
e
Cs2CO3 (0.5 mmol).

Y. Zhu, Y. Gong / Tetrahedron 72 (2016) 3436e3442
3439
According to the above investigation,
a
possible reaction
mass spectra (HRMS) were recorded with a Bruker TOF-Q spec-
trometer in the EI mode. Melting points were recorded with
a melting point detector. All reactions were monitored by TLC
mechanism was proposed and depicted in Scheme 4. The reaction
was initiated by a simple 1,2-elimination of HCl, giving a highly
reactive cyclopropene intermediate I. Next, sodium arylsulfinate
attacked the intermediate I via Michael addition to furnish the
formal substitution compound 3aa under basic conditions. Sub-
sequent esterolysis and decarboxylation of 3aa provided the
cyclopropyl aryl sulfone 4aa. Though the activation role of aryl-
sulfonyl group is still kept unclear, we presumed that its orientation
and coordination ability with cesium ion plays a crucial role in the
esterolysis process depicted in Scheme 4, since the analogous
methylsulfonyl group did not have the role. In addition, we spec-
ulated that stereoelectronic and steric effects between aroyl and
sulfonyl groups played the key role for the excellently diaster-
eoselective formation of trans-4aa during the final protonation step
as shown in Scheme 4.
ꢀ
analysis using silica gel 60 A F-254 thin layer plates and visualized
by UV. Flash column chromatography was performed on silica gel
ꢀ
60 A, 10e40
mm. All reagents and solvents were of commercial
grade and purified prior to use when necessary. Unless otherwise
noted, 2-acyl-1-chlorocyclopropanecarboxylate were synthesized
according to literature.2
4.2. Typical procedure for the synthesis of cyclopropyl aryl
sulfones 4
Compounds 2-benzoyl-1-chlorocyclopropanecarboxylate 1a
(50 mg, 0.2 mmol), sodium benzenesulfinate 2a (66 mg, 0.4 mmol)
and Cs2CO3 (131 mg, 0.4 mmol) were putted into 2 mL of DMSO at
room temperature, and then the reaction mixture was heated and
stirred at 80 ꢁC. The reaction was followed by TLC until all the
substrate 1a disappeared. The reaction was cooled to room tem-
perature and was diluted with water (10 mL). Further treatment
was followed by extraction with CH2Cl2 (2ꢂ20 mL). The combined
organic extracts were washed with H2O (20 mL) and brine
(3ꢂ20 mL), dried with anhydrous Na2SO4, filtered, and concen-
trated under reduced pressure. The residue was purified by silica
gel column chromatography using petroleum ether-EtOAc as eluent
to afford the corresponding product 4aa. Unless otherwise speci-
fied, all other products 3 and 4 were obtained according to this
typical procedure. All the products 4 with trans configuration
prepared in this work are racemic.
4.3. Phenyl((1S,2R)-2-(phenylsulfonyl)cyclopropyl)methanone
(4aa)
White solid (51 mg, 89% yield). Mp 120.7e122.3 ꢁC. 1H NMR
(400 MHz, CDCl3, 25 ꢁC, TMS):
d
¼7.99 (d, J¼7.7 Hz, 2H, ArH), 7.94 (d,
J¼7.7 Hz, 2H, ArH), 7.66 (dd, J¼13.8, 6.2 Hz, 1H, ArH), 7.59 (dd,
J¼15.5, 7.5 Hz, 3H, ArH), 7.49 (t, J¼7.7 Hz, 2H, ArH), 3.52 (ddd, J¼9.7,
5.7, 4.2 Hz,1H, CH-cyclo), 3.18 (ddd, J¼9.8, 5.8, 4.2 Hz,1H, CH-cyclo),
1.90e1.82 (m, 1H, CH2-cyclo), 1.74 (dt, J¼8.5, 5.3 Hz, 1H, CH2-cyclo).
13C NMR (101 MHz, CDCl3, 25 ꢁC, TMS):
d
¼195.2, 139.9, 136.49,
Scheme 4. Proposed mechanism for the tandem reaction.
133.9, 129.5, 129.4, 128.8, 128.4, 127.7, 42.2, 23.0, 15.3. IR (neat):
n
3025, 2923, 1731, 1664, 1592, 1447, 1385, 1306, 1266, 1225, 1149,
1084, 1063, 1023, 981, 916, 861, 794 cmꢀ1. HRMS (EI): m/z calcd for
3. Conclusions
C
16H15O3S [MþH]þ: 287.0742, found: 287.0745.
In summary, a novel and metal-free method for the high
regioselective addition of the electron-deficient reactive cyclo-
propene intermediate generated in situ from 2-acyl-1-
chlorocyclopropanecarboxylate with sodium sulfinate has been
developed under mild conditions. A broad range of 1-aroylsulfonyl-
2-aroylcyclopropane derivatives, which involves the 1,2-
elimination/addition/esterolysis/decarboxylation pathway, was
obtained in up to 89% yield with excellent dr value. In addition, the
synthetically useful research of this special electron-deficient
cyclopropene intermediate generated in situ is currently un-
derway in our laboratory.
4.4. ((1S,2R)-2-(Phenylsulfonyl)cyclopropyl)(p-tolyl)meth-
anone (4ba)
Light yellow solid (48 mg, 80% yield). Mp 129.3e131.1 ꢁC. 1H
NMR (400 MHz, CDCl3, 25 ꢁC, TMS):
d
¼7.97e7.86 (m, 4H, ArH),
7.68e7.62 (m, 1H, ArH), 7.56 (dd, J¼10.5, 4.7 Hz, 2H, ArH), 7.30e7.26
(m, 2H, ArH), 3.55e3.44 (m, 1H, CH-cyclo), 3.17 (ddd, J¼8.5, 5.8,
4.1 Hz, 1H, CH-cyclo), 2.42 (s, 3H, CH3), 1.83 (tt, J¼13.8, 6.4 Hz, 1H,
CH2-cyclo), 1.72 (ddd, J¼8.5, 5.8, 4.7 Hz, 1H, CH2-cyclo). 13C NMR
(101 MHz, CDCl3, 25 ꢁC, TMS):
129.5, 129.5, 128.6, 127.7, 42.1, 22.9, 21.7, 15.2. IR (neat):
d
¼194.6, 144.9, 139.89, 133.9, 133.9,
n
3027,
4. Experimental section
4.1. General information
2922, 1734, 1662, 1603, 1447, 1418, 1383, 1307, 1233, 1209, 1178,
1148, 1086, 1061, 1033, 985, 920, 859, 817, 748 cmꢀ1. HRMS (EI): m/z
calcd for C17H17O3S [MþH]þ: 301.0898, found: 301.0888.
All isolated compounds were characterized on the basis of 1H
NMR and 13C NMR spectroscopic data, IR spectra, and HRMS data.
All 1H NMR and 13C NMR spectra were recorded on a 400 MHz
spectrometer with solvent resonances as the internal standard (1H
NMR: CDCl3 at 7.26 ppm; 13C NMR: CDCl3 at 77.0 ppm). Infrared
spectra were recorded with a FTIR spectrometer. High-resolution
4.5. (4-Methoxyphenyl)((1S,2R)-2-(phenylsulfonyl)-
cyclopropyl)methanone (4ca)
Light yellow solid (43 mg, 68% yield). Mp 85.6e87.3 ꢁC. 1H NMR
(400 MHz, CDCl3, 25 ꢁC, TMS):
J¼7.2 Hz, 2H, ArH), 7.65 (t, J¼7.4 Hz, 1H, ArH), 7.57 (t, J¼7.6 Hz, 2H,
d
¼7.97 (t, J¼7.5 Hz, 2H, ArH), 7.93 (d,

3440
Y. Zhu, Y. Gong / Tetrahedron 72 (2016) 3436e3442
ArH), 6.95 (d, J¼8.9 Hz, 2H, ArH), 3.88 (s, 3H, OCH3), 3.51e3.43 (m,
1H, CH-cyclo), 3.15 (ddd, J¼8.6, 5.8, 4.2 Hz, 1H, CH-cyclo), 1.86e1.77
(m, 1H, CH2-cyclo), 1.71 (dt, J¼8.5, 5.2 Hz, 1H, CH2-cyclo). 13C NMR
1381, 1307, 1267, 1227, 1207, 1183, 1150, 1085, 1067, 1028, 982, 920,
863, 839, 745 cmꢀ1. HRMS (EI): m/z calcd for C22H19O3S [MþH]þ:
363.1055, found: 363.1051.
(101 MHz, CDCl3, 25 ꢁC, TMS):
d
¼193.3, 164.2, 139.9, 133.8, 130.9,
130.8, 129.5, 129.3, 129.1, 127.6, 114.0, 113.9, 55.6, 41.9, 22.7, 15.1. IR
(neat): 3026, 2929, 1735, 1657, 1600, 1570, 1510, 1450, 1427, 1383,
4.10. (Furan-2-yl)((1S,2R)-2-(phenylsulfonyl)cyclopropyl)-
methanone (4ha)
n
1308, 1233, 1170, 1149, 1085, 1064, 1024, 980, 888, 856, 819,
762 cmꢀ1. HRMS (EI): m/z calcd for C17H17O4S [MþH]þ: 317.0848,
found: 317.0844.
White solid (43 mg, 78% yield). Mp 140.6e142.2 ꢁC. 1H NMR
(400 MHz, CDCl3, 25 ꢁC, TMS):
d¼7.95e7.91 (m, 2H, ArH), 7.70e7.62
(m, 2H, ArH), 7.57 (t, J¼7.6 Hz, 2H, ArH), 7.31 (t, J¼4.3 Hz, 1H, ArH),
6.59 (dd, J¼3.6,1.6 Hz,1H, ArH), 3.43 (ddd, J¼9.6, 5.7, 4.2 Hz,1H, CH-
cyclo), 3.15 (ddd, J¼8.6, 5.9, 4.1 Hz, 1H, CH-cyclo), 1.89e1.78 (m, 1H,
CH2-cyclo),1.78e1.66 (m, 1H, CH2-cyclo). 13C NMR (101 MHz, CDCl3,
4.6. (4-Chlorophenyl)((1S,2R)-2-(phenylsulfonyl)-cyclopropyl)
methanone (4da)
Light yellow solid (56 mg, 88% yield). Mp 122.8e123.6 ꢁC. 1H
25 ꢁC, TMS):
112.8, 41.8, 23.2, 14.9. IR (neat): n
d
¼183.4, 152.2, 147.6, 139.8, 133.9, 129.4, 127.7, 118.6,
NMR (400 MHz, CDCl3, 25 ꢁC, TMS):
d
¼7.93 (ddd, J¼8.8, 6.2, 5.1 Hz,
3039, 2924, 1735, 1664, 1568,
4H, ArH), 7.72e7.61 (m, 1H, ArH), 7.57 (dd, J¼17.0, 9.6 Hz, 2H, ArH),
7.51e7.41 (m, 2H, ArH), 3.54e3.41 (m, 1H, CH-cyclo), 3.17 (ddd,
J¼8.5, 5.9, 4.1 Hz, 1H, CH-cyclo), 1.85 (ddd, J¼9.2, 5.8, 4.8 Hz, 1H,
CH2-cyclo), 1.74 (ddd, J¼8.5, 5.7, 4.9 Hz, 1H, CH2-cyclo). 13C NMR
1466, 1403, 1381, 1308, 1286, 1234, 1196, 1153, 1084, 1039, 1015, 992,
920, 879, 855, 794, 755 cmꢀ1. HRMS (EI): m/z calcd for C14H13O4S
[MþH]þ: 277.0535, found: 277.0532.
(101 MHz, CDCl3, 25 ꢁC, TMS):
129.8, 129.5, 129.2, 127.7, 42.3, 22.9, 15.4. IR (neat):
d
¼194.0, 140.5, 139.7, 134.7, 134.0,
4.11. ((1S,2R)-2-(Phenylsulfonyl)cyclopropyl)(thiophen-2-yl)
methanone (4ia)
n
3095, 3039,
1676, 1584, 1483, 1446, 1402, 1374, 1310, 1287, 1258, 1212, 1148,
1083, 1022, 981, 915, 889, 866, 779, 754 cmꢀ1. HRMS (EI): m/z calcd
for C16H14ClO3S [MþH]þ: 321.0352, found: 321.0350.
Yellow solid (43 mg, 78% yield). Mp 120.1e121.8 ꢁC. 1H NMR
(400 MHz, CDCl3, 25 ꢁC, TMS):
d¼7.95e7.90 (m, 2H, ArH), 7.88 (dd,
J¼3.8, 0.8 Hz, 1H, ArH), 7.72 (dd, J¼4.9, 0.8 Hz, 1H, ArH), 7.66 (t,
J¼7.4 Hz, 1H, ArH), 7.57 (t, J¼7.6 Hz, 2H, ArH), 7.18 (dd, J¼4.7, 4.0 Hz,
1H, ArH), 3.43e3.33 (m, 1H, CH-cyclo), 3.18 (ddd, J¼8.6, 5.9, 4.1 Hz,
1H, CH-cyclo), 1.84 (ddd, J¼9.2, 5.8, 5.0 Hz, 1H, CH2-cyclo), 1.74 (dt,
J¼8.6, 5.3 Hz, 1H, CH2-cyclo). 13C NMR (101 MHz, CDCl3, 25 ꢁC,
4.7. (4-Bromophenyl)((1S,2R)-2-(phenylsulfonyl)-cyclopropyl)
methanone (4ea)
White solid (43 mg, 60% yield). Mp 117.4e118.2 ꢁC. 1H NMR
(400 MHz, CDCl3, 25 ꢁC, TMS):
d
¼7.96e7.90 (m, 2H, ArH), 7.84 (d,
TMS):
d
¼187.4, 143.4, 139.8, 135.2, 133.9, 133.2, 129.5, 128.6, 127.7,
J¼8.6 Hz, 2H, ArH), 7.71e7.55 (m, 5H, ArH), 3.45 (ddd, J¼9.5, 5.8,
4.1 Hz, 1H, CH-cyclo), 3.17 (ddd, J¼8.5, 5.9, 4.1 Hz, 1H, CH-cyclo),
1.90e1.81 (m, 1H, CH2-cyclo), 1.78e1.70 (m, 1H, CH2-cyclo). 13C
41.9, 23.9, 15.1. IR (neat):
n 3022, 2924, 1731, 1652, 1515, 1447, 1413,
1381, 1353, 1305, 1246, 1223, 1194, 1147, 1086, 1065, 1022, 957, 920,
864, 843, 727 cmꢀ1. HRMS (EI): m/z calcd for C14H13O3S2 [MþH]þ:
293.0306, found: 293.0301.
NMR (101 MHz, CDCl3, 25 ꢁC, TMS):
d¼194.2, 139.7, 135.1, 133.9,
132.2, 129.9, 129.5, 129.3, 127.7, 42.3, 22.9, 15.4. IR (neat): 3029,
n
2924, 1734, 1671, 1583, 1481, 1447, 1422, 1402, 1382, 1308, 1226,
1175, 1148, 1069, 1035, 1009, 985, 921, 857, 826, 750 cmꢀ1. HRMS
(EI): m/z calcd for C16H14BrO3S [MþH]þ: 364.9847, found: 364.9841.
4.12. (Naphthalen-4-yl)((1S,2R)-2-(phenylsulfonyl)-
cyclopropyl)methanone (4ja)
Yellow solid (59 mg, 72% yield). Mp 133.6e134.7 ꢁC. 1H NMR
4.8. (2-Bromophenyl)((1S,2R)-2-(phenylsulfonyl)-cyclopropyl)
methanone (4fa)
(400 MHz, CDCl3, 25 ꢁC, TMS):
d
¼8.42 (d, J¼8.3 Hz,1H, ArH), 7.94 (d,
J¼8.2 Hz, 1H, ArH), 7.92e7.85 (m, 3H, ArH), 7.79 (dd, J¼9.3, 7.9 Hz,
1H, ArH), 7.60 (t, J¼7.4 Hz, 1H, ArH), 7.47 (dddd, J¼15.5, 11.5, 8.9,
5.9 Hz, 5H, ArH), 3.45e3.35 (m, 1H, CH-cyclo), 3.21 (ddd, J¼8.5, 5.9,
4.1 Hz, 1H, CH-cyclo), 1.80 (ddt, J¼10.5, 8.5, 4.7 Hz, 2H, CH2-cyclo).
Yellowish oil (35 mg, 48% yield). 1H NMR (400 MHz, CDCl3, 25 ꢁC,
TMS):
d
¼7.93 (d, J¼7.3 Hz, 2H, ArH), 7.62 (dq, J¼30.7, 7.6 Hz, 4H,
ArH), 7.45e7.30 (m, 3H, ArH), 3.39e3.30 (m, 1H, CH-cyclo), 3.26
(ddd, J¼8.8, 6.0, 4.2 Hz, 1H, CH-cyclo), 1.94e1.84 (m, 1H, CH2-cyclo),
1.78 (dt, J¼8.7, 5.2 Hz, 1H, CH2-cyclo). 13C NMR (101 MHz, CDCl3,
13C NMR (101 MHz, CDCl3, 25 ꢁC, TMS):
d¼198.27, 139.87, 134.94,
133.94, 133.86, 133.66, 129.96, 129.53, 129.04, 128.58, 128.28,
127.75, 126.72, 125.50, 124.49, 42.80, 26.28, 15.83. IR (neat): 3029,
2924, 1729, 1663, 1585, 1506, 1447, 1400, 1372, 1308, 1278, 1231,
n
25 ꢁC, TMS):
d
¼198.7, 140.2, 139.7, 133.9, 133.9, 132.6, 129.5, 127.8,
127.6, 119.4, 43.4, 26.9, 16.7. IR (neat):
n
3062, 2923, 1690, 1586,
1149, 1101, 1069, 1025, 960, 920, 889, 864, 809, 778, 733 cmꢀ1
.
1468, 1445, 1430, 1379, 1315, 1287, 1213, 1188, 1152, 1087, 1069,
HRMS (EI): m/z calcd for C20H17O3S [MþH]þ: 337.0898, found:
1026, 985, 952, 917, 861, 748 cmꢀ1. HRMS (EI): m/z calcd for
337.0892.
C
16H14BrO3S [MþH]þ: 364.9847, found: 364.9833.
4.13. (1,9-Dihydropyren-5-yl)((1S,2R)-2-(phenylsulfonyl)-cy-
4.9. (4-Biphenyl)((1S,2R)-2-(phenylsulfonyl)cyclopropyl)-
clopropyl)methanone (4ka)
methanone (4ga)
Yellow solid (59 mg, 72% yield). Mp 162.8e163.2 ꢁC. 1H NMR
Light yellow solid (24 mg, 33% yield). Mp 176.5e178.1 ꢁC. 1H
(400 MHz, CDCl3, 25 ꢁC, TMS):
d
¼8.77 (d, J¼9.4 Hz,1H, ArH), 8.35 (d,
NMR (400 MHz, CDCl3, 25 ꢁC, TMS):
d
¼8.06 (d, J¼8.4 Hz, 2H, ArH),
J¼8.0 Hz, 1H, ArH), 8.21 (d, J¼7.7 Hz, 2H, ArH), 8.18e8.07 (m, 3H,
ArH), 8.06e7.96 (m, 4H, ArH), 7.69e7.62 (m, 1H, ArH), 7.58 (t,
J¼7.5 Hz, 2H, ArH), 3.67e3.60 (m, 1H, CH-cyclo), 3.38 (ddd, J¼8.1,
6.2, 4.1 Hz, 1H, CH-cyclo), 2.01e1.92 (m, 2H, CH2-cyclo). 13C NMR
7.95 (d, J¼7.5 Hz, 2H, ArH), 7.74e7.69 (m, 2H, ArH), 7.65 (dd, J¼8.7,
7.4 Hz, 3H, ArH), 7.57 (dd, J¼15.1, 7.7 Hz, 2H, ArH), 7.49 (t, J¼7.4 Hz,
2H, ArH), 7.42 (t, J¼7.3 Hz, 1H, ArH), 3.56 (ddd, J¼9.6, 5.7, 4.2 Hz, 1H,
CH-cyclo), 3.20 (ddd, J¼8.6, 5.8, 4.2 Hz, 1H, CH-cyclo), 1.88 (dt,
J¼9.3, 5.3 Hz, 1H, CH2-cyclo), 1.80e1.72 (m, 1H, CH2-cyclo). 13C NMR
(101 MHz, CDCl3, 25 ꢁC, TMS):
d
¼198.4, 134.0, 134.4, 133.9, 131.1,
131.0, 130.4, 130.03, 130.00, 129.5, 127.8, 127.1, 127.0, 126.6, 126.5,
126.4, 124.8, 124.4, 124.1, 43.0, 26.7, 16.0. IR (neat): 3043, 2957,
2922,1735,1659,1587, 1537, 1502,1446,1381,1311,1259,1214,1184,
1145, 1116, 1080, 1021, 982, 959, 918, 889, 844, 782, 765, 747 cmꢀ1
(101 MHz, CDCl3, 25 ꢁC, TMS):
d
¼194.7, 146.6, 139.9, 139.6, 135.1,
n
133.9, 129.5, 129.1, 129.0, 128.5, 127.7, 127.5, 127.3, 42.2, 23.1, 15.4. IR
(neat): 3027, 2923, 1733, 1663, 1601, 1559, 1516, 1481, 1448, 1406,
n
.

Y. Zhu, Y. Gong / Tetrahedron 72 (2016) 3436e3442
3441
HRMS (EI): m/z calcd for C26H21O3S [MþH]þ: 413.1211, found:
7.80 (d, J¼8.3 Hz, 2H, ArH), 7.35 (d, J¼8.0 Hz, 2H, ArH), 7.28 (d,
J¼8.0 Hz, 2H, ArH), 3.51e3.44 (m, 1H, CH-cyclo), 3.14 (ddd, J¼8.5,
5.8, 4.1 Hz, 1H, CH-cyclo), 2.44 (s, 3H, CH3), 2.43 (s, 3H, CH3), 1.81
(ddd, J¼9.2, 5.8, 4.7 Hz, 1H, CH2-cyclo), 1.73e1.69 (m, 1H, CH2-cy-
413.1209.
4.14. Phenyl((1S,2R)-2-tosylcyclopropyl)methanone (4ab)
Light yellow solid (30 mg, 50% yield). Mp 117.4e118.6 ꢁC. 1H
clo). 13C NMR (101 MHz, CDCl3, 25 ꢁC, TMS):
d¼194.7, 144.9, 144.9,
137.0, 134.0, 130.1, 129.5, 128.6, 127.7, 42.2, 22.9, 21.7, 21.6, 15.2. IR
(neat): 3028, 2923, 1732, 1661, 1602, 1491, 1455, 1419, 1383, 1305,
NMR (400 MHz, CDCl3, 25 ꢁC, TMS):
d
¼8.04e7.95 (m, 2H, ArH),
n
7.79 (t, J¼9.8 Hz, 2H, ArH), 7.61 (t, J¼7.4 Hz, 1H, ArH), 7.48 (dd,
J¼17.0, 9.5 Hz, 2H, ArH), 7.36 (d, J¼8.0 Hz, 2H, ArH), 3.55e3.45 (m,
1H, CH-cyclo), 3.16 (ddd, J¼8.6, 5.8, 4.2 Hz, 1H, CH-cyclo), 2.45 (s,
3H, CH3), 1.84 (ddd, J¼9.3, 5.7, 4.8 Hz, 1H, CH2-cyclo), 1.76e1.68 (m,
1271, 1232, 1210, 1178, 1145, 1085, 1064, 1032, 986, 919, 860, 818,
759, 716 cmꢀ1. HRMS (EI): m/z calcd for C18H19O3S [MþH]þ:
315.1055, found: 315.1049.
1H, CH2-cyclo). 13C NMR (101 MHz, CDCl3, 25 ꢁC, TMS):
d¼195.3,
4.19. ((1S,2R)-2-(4-Chlorophenylsulfonyl)cyclopropyl)(p-tolyl)
methanone (4bd)
144.9, 136.9, 136.5, 133.8, 130.1, 128.8, 128.4, 127.7, 42.4, 23.1, 21.6,
15.3. IR (neat): 3046, 2923, 1734, 1682, 1593, 1456, 1383, 1317,
n
1268, 1217, 1145, 1086, 1025, 986, 917, 883, 815, 798, 746 cmꢀ1
.
Light yellow solid (22 mg, 33% yield). Mp 156.2e157.1 ꢁC. 1H
HRMS (EI): m/z calcd for C17H17O3S [MþH]þ: 301.0898, found:
NMR (400 MHz, CDCl3, 25 ꢁC, TMS):
d
¼7.96e7.80 (m, 4H, ArH),
301.0879.
7.59e7.51 (m, 2H, ArH), 7.29 (t, J¼6.9 Hz, 2H, ArH), 3.49 (ddd, J¼9.6,
5.8, 4.1 Hz,1H, CH-cyclo), 3.15 (ddd, J¼8.5, 5.8, 4.1 Hz,1H, CH-cyclo),
2.44 (s, 3H, CH3), 1.82 (ddd, J¼9.3, 5.7, 4.8 Hz, 1H, CH2-cyclo), 1.72
(ddd, J¼8.5, 5.8, 4.8 Hz, 1H, CH2-cyclo). 13C NMR (101 MHz, CDCl3,
4.15. ((1S,2R)-2-(4-Methoxyphenylsulfonyl)cyclopropyl) (phe-
nyl)-methanone (4ac)
25 ꢁC, TMS):
d
¼194.4, 145.0, 140.7, 138.4, 133.9, 129.8, 129.6, 129.2,
Yellow solid (42 mg, 66% yield). Mp 122.3e123.4 ꢁC. 1H NMR
128.6, 41.9, 22.9, 21.7, 15.3. IR (neat): n 3039, 2920, 1733, 1663, 1604,
(400 MHz, CDCl3, 25 ꢁC, TMS):
d
¼7.99 (d, J¼7.4 Hz, 2H, ArH), 7.85 (d,
1574, 1470, 1423, 1386, 1322, 1269, 1232, 1205, 1177, 1147, 1086,
J¼8.9 Hz, 2H, ArH), 7.61 (t, J¼7.4 Hz, 1H, ArH), 7.49 (t, J¼7.7 Hz, 2H,
ArH), 7.03 (t, J¼7.4 Hz, 2H, ArH), 3.88 (s, 3H, OCH3), 3.49 (ddd, J¼9.5,
5.7, 4.2 Hz,1H, CH-cyclo), 3.15 (ddd, J¼8.6, 5.8, 4.2 Hz,1H, CH-cyclo),
1.87e1.79 (m,1H, CH2-cyclo),1.75e1.69 (m,1H, CH2-cyclo). 13C NMR
1035, 1012, 990, 861, 827, 761, 721 cmꢀ1. HRMS (EI): m/z calcd for
C
17H16ClO3S [MþH]þ: 335.0509, found: 335.0504.
The procedure for crystal growth: Compound 4bd was soluble in
mixtures of chloroform and petroleum ether, crystal could be
prepared by the slow volatilization of solvents at room
temperature.
(101 MHz, CDCl3, 25 ꢁC, TMS):
129.9, 128.8, 128.4, 114.7, 55.7, 42.6, 23.1, 15.4. IR (neat):
d¼195.3, 163.9, 136.5, 133.8, 131.4,
n
3044,
2936, 1734, 1672, 1594, 1497, 1387, 1297, 1262, 1222, 1146, 1089,
1024, 987, 858, 801, 741 cmꢀ1. HRMS (EI): m/z calcd for C16H13O3S
[MþH]þ: 285.0585, found: 285.0577.
4.20. (4-Chlorophenyl)((1S,2R)-2-tosylcyclopropyl)meth-
anone (4db)
4.16. ((1S,2R)-2-(4-Chlorophenylsulfonyl)cyclopropyl)(phenyl)
-methanone (4ad)
Light yellow solid (42 mg, 63% yield). Mp 130.4e132.3 ꢁC. 1H
NMR (400 MHz, CDCl3, 25 ꢁC, TMS):
d
¼7.94 (dd, J¼11.4, 9.6 Hz, 2H,
ArH), 7.80 (d, J¼8.3 Hz, 2H, ArH), 7.49e7.44 (m, 2H, ArH), 7.36 (d,
J¼8.0 Hz, 2H, ArH), 3.44 (ddd, J¼9.5, 5.8, 4.1 Hz, 1H, CH-cyclo), 3.14
(ddd, J¼8.5, 5.9, 4.1 Hz, 1H, CH-cyclo), 2.45 (s, 3H, CH3), 1.83 (ddd,
Light yellow solid (33 mg, 51% yield). Mp 127.8e129.1 ꢁC. 1H
NMR (400 MHz, CDCl3, 25 ꢁC, TMS):
d
¼7.99 (d, J¼7.5 Hz, 2H, ArH),
7.87 (d, J¼8.5 Hz, 2H, ArH), 7.63 (t, J¼7.6 Hz, 1H, ArH), 7.57e7.47 (m,
4H, ArH), 3.56e3.47 (m, 1H, CH-cyclo), 3.22e3.13 (m, 1H, CH-cyclo),
1.88e1.80 (m, 1H, CH2-cyclo), 1.73 (dt, J¼8.6, 5.3 Hz, 1H, CH2-cyclo).
J¼9.2, 5.8, 4.8 Hz, 1H, CH2-cyclo), 1.79e1.67 (m, 1H, CH2-cyclo). 13
C
NMR (101 MHz, CDCl3, 25 ꢁC, TMS):
d
¼194.1, 145.0, 140.4, 136.8,
134.8, 130.1, 129.8, 129.2, 127.7, 42.5, 22.9, 21.6, 15.4. IR (neat):
n
13C NMR (101 MHz, CDCl3, 25 ꢁC, TMS):
d
¼194.9, 140.7, 138.3, 136.3,
3042, 2922, 1736, 1667, 1588, 1487, 1425, 1404, 1384, 1318, 1289,
1266,1174,1147, 1116,1089,1066,1034, 986, 925, 862, 834, 814, 780,
755 cmꢀ1. HRMS (EI): m/z calcd for C17H16ClO3S [MþH]þ: 335.0509,
found: 335.0501.
133.9, 129.8, 129.2, 128.9, 128.4, 42.0, 23.1, 15.4. IR (neat):
n
3047,
2923, 1732, 1671, 1578, 1473, 1449, 1389, 1308, 1270, 1222, 1151,
1086, 1018, 984, 919, 887, 856, 830, 794, 760, 731 cmꢀ1. HRMS (EI):
m/z calcd for C16H14ClO3S [MþH]þ: 321.0352, found: 321.0350.
4.21. ((1S,2R)-2-(4-Chlorophenylsulfonyl)cyclopropyl)(4-
4.17. ((1S,2R)-2-(2-Thienylsulfonyl)cyclopropyl)(phenyl)-
chlorophenyl)methanone (4dd)
methanone (4ae)
Light yellow solid (30 mg, 43% yield). Mp 160.4e161.5 ꢁC. 1H
Yellow solid (40 mg, 68% yield). Mp 113.4e114.2 ꢁC. 1H NMR
NMR (400 MHz, CDCl3, 25 ꢁC, TMS):
d¼7.97e7.92 (m, 2H, ArH),
(400 MHz, CDCl3, 25 ꢁC, TMS):
d
¼8.04e7.98 (m, 2H, ArH), 7.73 (ddd,
7.88e7.84 (m, 2H, ArH), 7.58e7.54 (m, 2H, ArH), 7.50e7.46 (m, 2H,
ArH), 3.46 (ddd, J¼9.5, 5.8, 4.1 Hz, 1H, CH-cyclo), 3.16 (ddd, J¼8.5,
5.9, 4.1 Hz, 1H, CH-cyclo), 1.83 (ddd, J¼9.2, 5.8, 4.8 Hz, 1H, CH2-
cyclo), 1.73 (ddd, J¼8.5, 5.7, 4.9 Hz, 1H, CH2-cyclo). 13C NMR
J¼6.1, 4.3, 1.1 Hz, 2H, ArH), 7.62 (t, J¼7.4 Hz, 1H, ArH), 7.50 (t,
J¼7.7 Hz, 2H, ArH), 7.16 (dd, J¼4.8, 3.9 Hz,1H, ArH), 3.54 (ddd, J¼9.6,
5.8, 4.1 Hz, 1H, CH-cyclo), 3.30 (ddd, J¼8.6, 5.8, 4.1 Hz, 1H, CH-
cyclo), 1.95e1.86 (m, 1H, CH2-cyclo), 1.82e1.75 (m, 1H, CH2-cyclo).
(101 MHz, CDCl3, 25 ꢁC, TMS):
129.9, 129.8, 129.2, 129.2, 42.1, 22.9, 15.5. IR (neat): n
d
¼193.8, 140.8, 140.6, 138.2, 134.6,
3090, 2924,
1730,1670,1585,1476,1426,1400,1308,1276,1221,1178,1146,1087,
13C NMR (101 MHz, CDCl3, 25 ꢁC, TMS):
d
¼195.0, 140.5, 136.3, 134.2,
133.9, 128.9, 128.5, 128.0, 43.4, 23.7, 15.8. IR (neat): 3088, 3048,
n
1733, 1676, 1595, 1449, 1401, 1380, 1314, 1265, 1225, 1142, 1097,
1068, 1016, 984, 863, 736 cmꢀ1. HRMS (EI): m/z calcd for C14H13O3S2
[MþH]þ: 293.0306, found: 293.0298.
1036, 991, 865, 766, 751 cmꢀ1
. HRMS (EI): m/z calcd for
C
16H13Cl2O3S [MþH]þ: 354.9962, found: 354.9951.
4.22. (Thiophen-2-yl)((1S,2R)-2-tosylcyclopropyl)methanone
4.18. p-Tolyl((1S,2R)-2-tosylcyclopropyl)methanone (4bb)
(4ib)
Light yellow solid (32 mg, 51% yield). Mp 143.7e145.2 ꢁC. 1H
Light yellow solid (31 mg, 51% yield). Mp 126.3e127.6 ꢁC. 1H
NMR (400 MHz, CDCl3, 25 ꢁC, TMS):
d¼7.89 (d, J¼8.2 Hz, 2H, ArH),
NMR (400 MHz, CDCl3, 25 ꢁC, TMS):
d
¼7.88 (dd, J¼5.8, 4.9 Hz, 1H,

3442
Y. Zhu, Y. Gong / Tetrahedron 72 (2016) 3436e3442
ArH), 7.79 (t, J¼7.9 Hz, 2H, ArH), 7.74e7.71 (m, 1H, ArH), 7.36 (d,
J¼8.1 Hz, 2H, ArH), 7.18 (dd, J¼4.8, 4.0 Hz, 1H, ArH), 3.40e3.33 (m,
1H, CH-cyclo), 3.16 (ddd, J¼8.7, 5.9, 4.1 Hz, 1H, CH-cyclo), 2.44 (s,
3H, CH3), 1.82 (ddd, J¼9.2, 5.8, 4.9 Hz, 1H, CH2-cyclo), 1.72 (dt, J¼8.6,
5.2 Hz, 1H, CH2-cyclo). 13C NMR (101 MHz, CDCl3, 25 ꢁC, TMS):
965, 929, 856, 779, 763 cmꢀ1. HRMS (EI): m/z calcd for C14H17O5S
[MþH]þ: 297.0797, found: 297.0793.
Acknowledgements
d
¼187.5, 144.9, 143.5, 136.8, 135.1, 133.2, 130.1, 128.6, 127.7, 42.1,
This work was financially supported by grants from National
Science Foundation of China (no. 21472053, 21172082). The Center
of Analysis and Testing of Huazhong University of Science and
Technology is gratefully acknowledged for characterization of the
new compounds.
23.9, 21.7, 15.1. IR (neat): 3022, 2923, 1724, 1645, 1594, 1515, 1454,
n
1416, 1382, 1293, 1247, 1222, 1189, 1142, 1109, 1084, 1065, 1020, 957,
921, 864, 842, 818, 758 cmꢀ1. HRMS (EI): m/z calcd for C15H15O3S2
[MþH]þ: 307.0463, found: 307.0461.
Supplementary data
4.23. ((1S,2R)-2-(4-Chlorophenylsulfonyl)cyclopropyl)-(thio-
phen-2-yl)methanone (4id)
Supplementary data (Copies of 1H and 13C NMR spectra for all
compounds; X-ray structure of 4bc.) related to this article can be
found at http://dx.doi.org/10.1016/j.tet.2016.04.062.
Light yellow solid (13 mg, 20% yield). Mp 170.4e171.8 ꢁC. 1H
NMR (400 MHz, CDCl3, 25 ꢁC, TMS):
d
¼7.89 (dd, J¼3.8, 1.0 Hz, 1H,
ArH), 7.88e7.83 (m, 2H, ArH), 7.74 (dd, J¼5.0, 1.0 Hz, 1H, ArH),
7.58e7.52 (m, 2H, ArH), 7.20 (dd, J¼4.9, 3.9 Hz, 1H, ArH),
3.44e3.33 (m, 1H, CH-cyclo), 3.21e3.12 (m, 1H, CH-cyclo), 1.83
(ddd, J¼9.2, 5.8, 4.9 Hz, 1H, CH2-cyclo), 1.78e1.71 (m, 1H, CH2-
References and notes
1. For selected recent examples, see: (a) Fisher, L. A.; Smith, N. J.; Fox, J. M. J. Org. Chem.
2013, 78, 3342e3348; (b) Liu, Y.; Yu, Q.; Ma, S. M. Eur. J. Org. Chem. 2013,
3033e3040; (c) Young, P. C.; Hadfield, M. S.; Arrowsmith, L.; Macleod, K. M.; Mudd,
R. J.; Jordan-Hore, J. A.; Lee, A. Org. Lett. 2012, 14, 898e901; (d) Liu, Y.; Ma, S. M. Org.
Lett. 2012, 14, 720e723; (e) Miege, F.; Meyer, C.; Cossy, J. Chem.dEur. J. 2012, 18,
7810e7822; (f) Miege, F.; Meyer, C.; Cossy, J. Angew. Chem. 2011, 123, 6054 Angew.
Chem. Int. Ed. 2011, 50, 5932e5937; (g) Liu, Y.;Ma, S. M. Chem. Sci. 2011, 2, 811e814;
(h) Phan, D. H. T.; Kou, K. G. M.; Dong, V. M. J. Am. Chem. Soc. 2010, 132,
16354e16355; (i) Chen, S. J.; Ren, J.; Wang, Z. W. Tetrahedron 2009, 65, 9146e9151;
(j) Sherrill, W. M.; Rubin, M. J. Am. Chem. Soc. 2008,130,13804e13809; (k) Alnasleh,
B. K.; Sherrill, W. M.; Rubin, M. Org. Lett. 2008,10, 3231e3234; (l) Lee, G. A.; Chen, K.
C. Org. Lett. 2008, 10, 1843e1845; (m) Zhu, Z. B.; Shi, M. Chem.dEur. J. 2008, 14,
10219e10222; (n) Chuprakov, S.; D. Malyshev, A.; Trofimov, A.; Gevorgyan, V. J. Am.
Chem. Soc. 2007, 129, 14868e14869; (o) Diev, V. V.; Stetsenko, O. N.; Tung, T. Q.;
Kopf, J.; Kostikov, R. R.; Molchanov, A. P. J. Org. Chem. 2008, 73, 2396e2399; (p)
Chuprakov, S.; Gevorgyan, V. Org. Lett. 2007, 9, 4463e4466; (q) Diev, V. V.; Kostikov,
R. R.; Gleiter, R.; Molchanov, A. J. Org. Chem. 2006, 71, 4066e4077; (r) Yin, J. D.;
Chisholm, J. D. Chem. Commun. 2006, 632e634; (s) Pallerla, M. K.; Fox, J. M. Org. Lett.
2005, 7, 3593e3595; (t) Liao, L. A.; Yan, N.; Fox, J. M. Org. Lett. 2004, 6, 4937e4939;
(u) Zohar, E.; Marek, I. Org. Lett. 2004, 6, 341e343; (v) Orugunty, R. S.; Ghiviriga, I.;
Abboud, K. A.; Battiste, M. A.; Wright, D. L. J. Org. Chem. 2004, 69, 570e572; (w)
Zohar, E.; Ram, M.; Marek, I. Synlett 2004, 1288e1290.
2. Zhang, M.; Gong, Y. F.; Wang, W. Z. Eur. J. Org. Chem. 2013, 7372e7381.
3. (a) Ochiai, M.; Kitagawa, Y.; Toyonari, M.; Uemura, K.; Oshima, K.; Shiro, M. J.
Org. Chem. 1997, 62, 8001e8008; (b) Ochiai, M.; Kitogawa, Y.; Toyonari, M.;
Uemurat, K. Tetrahedron Lett. 1994, 35, 9407e9408; (c) Ochiai, M.; Oshima, K.;
Masaki, Y.; Kunishima, M.; Tanic, S. Tetrahedron Lett. 1993, 34, 4829e4830.
4. (a) Chang, Y. H.; Pinnick, H. W. J. Org. Chem. 1978, 43, 373e374; (b) Corey, E. J.;
Weatherhead-Kloster, R. A. Org. Lett. 2006, 8, 171e174.
5. (a) Baldwin, J. E.; Adlington, R. M.; Bebbington, D. Tetrahedron 1994, 50,
12015e12028; (b) Lai, M. T.; Oh, E.; Shih, Y.; Liu, H. W. J. Org. Chem. 1992, 57,
2471e2476.
cyclo). 13C NMR (101 MHz, CDCl3, 25 ꢁC, TMS):
d¼187.2, 143.3,
140.8, 138.2, 135.3, 133.3, 129.9, 129.2, 128.6, 41.8, 23.9, 15.2. IR
(neat): 3042, 2923, 1724, 1650, 1578, 1513, 1473, 1412, 1352, 1308,
n
1275, 1238, 1220, 1150, 1085, 1011, 957, 919, 861, 847, 831, 764,
740 cmꢀ1
326.9916, found: 326.9911.
.
HRMS (EI): m/z calcd for C14H12ClO3S2 [MþH]þ:
4.24. Ethyl 2-benzoyl-phenylsulfonylcyclopropanecarboxylate
(3aa)
Yellowish oil. 1H NMR (400 MHz, CDCl3, 25 ꢁC, TMS):
d
¼8.02e7.97 (m, 2H, ArH), 7.97e7.92 (m, 2H, ArH), 7.71 (t, J¼7.5 Hz,
1H, ArH), 7.63e7.56 (m, 3H, ArH), 7.45 (t, J¼7.7 Hz, 2H, ArH),
4.02e3.93 (m, 2H, COOEt), 3.66 (dd, J¼9.4, 7.5 Hz, 1H, CH-cyclo),
2.36 (dd, J¼7.4, 5.4 Hz, 1H, CH2-cyclo), 2.24 (dd, J¼9.5, 5.3 Hz, 1H,
CH2-cyclo), 0.97 (t, J¼7.1 Hz, 3H, COOEt). 13C NMR (101 MHz, CDCl3,
25 ꢁC, TMS):
d¼192.4, 163.3, 138.4, 136.4, 134.3, 133.8, 129.3, 129.1,
128.8, 128.6, 62.5, 53.3, 30.1, 18.4, 13.5. IR (neat): n 3065, 2985, 1736,
1681, 1598, 1582, 1449, 1372, 1310, 1228, 1202, 1161, 1138, 1081, 1017,
933, 871, 856, 827, 756, 728 cmꢀ1. HRMS (EI): m/z calcd for
C19H19O5S [MþH]þ: 359.0953, found: 359.0952.
6. Trost, B. M.; Cossy, J.; Burkes, J. J. Am. Chem. Soc. 1983, 105, 1052e1054.
7. Kazuta, Y.; Matsuda, A.; Shuto, S. J. Org. Chem. 2002, 67, 1669e1677.
8. Aïssa, C. J. Org. Chem. 2006, 71, 360e363.
9. Bhaskar Reddy, D.; Ramana Reddy, P. V.; Padmavathi, V. Phosphorus, Sulfur,
Silicon 1994, 90, 1e10.
4.25. Ethyl 2-benzoyl-1-methylsulfonylcyclopropanecarbox-
ylate (3af)
10. (a) Bhaskar Reddy, D.; Reddy, P. S.; Reddy, B. V.; Reddy, P. A. Synthsis 1987, 1,
74e75; (b) Padmaja, A.; Reddy, K. R.; Padmavathi, V.; Reddy, D. B. Collect. Czech.
Chem. Commun. 1998, 63, 835e841; (c) Papageorgiou, C. D.; Ley, S. V.; Gaunt, M.
J. Angew. Chem., Int. Ed. 2003, 42, 828e831.
11. (a) Balaji, T.; Bhaskar Reddy, D. Bull. Chem. Soc. Jpn. 1979, 52, 3434e3437; (b)
Tanaka, K.; Suzuki, H. J. Chem. Soc. Perkin. Trans. 1992, 2071e2074.
12. Bray, C. D.; Faveri, G. D. J. Org. Chem. 2010, 75, 4652e4655.
13. (a) Meninno, S.; Parrella, A.; Brancatelli, G.; Geremia, S.; Gaeta, C.; Talotta, C.;
Neri, P.; Lattanzi, A. Org. Lett. 2015, 17, 5100e5103; (b) Feng, J. B.; Gong, J. L.; Wu,
X. F. RSC Adv. 2014, 4, 29273e29275; (c) Secci, F.; Frongia, A.; Piras, P. P. Tet-
rahedron Lett. 2014, 55, 603e605.
Yellowish oil (32 mg, 53% yield). 1H NMR (400 MHz, CDCl3, 25 ꢁC,
TMS):
d
¼8.13e7.95 (m, 2H, ArH), 7.63 (t, J¼7.4 Hz, 1H, ArH), 7.52 (t,
J¼7.7 Hz, 2H, ArH), 4.29e4.14 (m, 2H, COOEt), 3.51 (dd, J¼9.7, 7.4 Hz,
1H, CH-cyclo), 3.25 (s, 3H, CH3), 2.38e2.25 (m, 1H, CH2-cyclo), 2.17
(dd, J¼9.8, 5.3 Hz, 1H, CH2-cyclo), 1.17 (t, J¼7.1 Hz, 3H, COOEt). 13
C
NMR (101 MHz, CDCl3, 25 ꢁC, TMS):
d
¼192.3, 164.2, 136.2, 134.1,
128.9, 128.5, 62.9, 51.3, 40.8, 29.8, 17.4, 13.6. IR (neat):
n 2984, 2935,
1730, 1682, 1597, 1581, 1450, 1372, 1312, 1229, 1161, 1129, 1097, 1019,