Studies on the factors controlling the stereoselectivity in electrophilic iodocyclization of alkylidenecyclopropyl ketones

Article abstract of DOI:10.1016/j.tet.2008.06.060

An efficient electrophilic iodocyclization of alkylidenecyclopropyl ketones with N-iodosuccinimide (NIS) or I₂ in aqueous CH₃CN affording 3-oxabicyclo[3.1.0]hexan-2-ols is described. NIS is a better electrophilic iodocyclization reagent than I₂. Four chiral centers were formed within one step. The stereochemistry was established by the X-ray diffraction studies of compounds 2e-2h, 2n, and 2c. It is quite interesting to observe that the substituent of the cyclopropane ring plays an important role in determining the relative stereochemistry at the 4-position: with R² being an acyl or ester group a mixture of (1S^*,2R^*,4S^*,5R^*)-2 (major) and (1R^*,2R^*,4R^*,5R^*)-2 (minor) was formed with moderate selectivity while the reaction of the substrates with R² being sulfonyl and p-methylphenylsulfonyl or R¹ being phenyl afforded (1R^*,2R^*,4S^*,5S^*)-2 or (1S^*,2R^*,4S^*,5R^*)-2f as the only product. The reaction is general for a range of different substrates to afford the products in moderate to high yields.

Full text of DOI:10.1016/j.tet.2008.06.060

Tetrahedron 64 (2008) 8899–8906
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Studies on the factors controlling the stereoselectivity in electrophilic
iodocyclization of alkylidenecyclopropyl ketones
*
Jie Chen, Lianghua Lu, Shengming Ma
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient electrophilic iodocyclization of alkylidenecyclopropyl ketones with N-iodosuccinimide (NIS)
or I2 in aqueous CH3CN affording 3-oxabicyclo[3.1.0]hexan-2-ols is described. NIS is a better electrophilic
iodocyclization reagent than I2. Four chiral centers were formed within one step. The stereochemistry
was established by the X-ray diffraction studies of compounds 2e–2h, 2n, and 2c. It is quite interesting to
observe that the substituent of the cyclopropane ring plays an important role in determining the relative
Received 17 February 2008
Received in revised form 10 June 2008
Accepted 17 June 2008
Available online 20 June 2008
stereochemistry at the 4-position: with R2 being an acyl or ester group a mixture of (1S
(major) and (1R ,2R ,4R ,5R )-2 (minor) was formed with moderate selectivity while the reaction of the
substrates with R2 being sulfonyl and p-methylphenylsulfonyl or R1 being phenyl afforded
(1R ,2R ,4S ,5S )-2 or (1S ,2R ,4S ,5R )-2f as the only product. The reaction is general for a range of
different substrates to afford the products in moderate to high yields.
Ó 2008 Elsevier Ltd. All rights reserved.
*
,2R
*
,4S
*
,5R
*
)-2
Keywords:
Iodocyclization
Alkylidenecyclopropyl ketones
Stereoselectivity
3-Oxabicyclo[3.1.0]hexan-2-ols
*
*
*
*
*
*
*
*
*
*
*
*
1. Introduction
proceed in a selective fashion leading to the synthesis of different
products by choice of different catalysts or reagents.
3-Oxabicyclo[3.1.0]hexan-2-ols are important units frequently
found in numerous biologically active natural products or pharma-
cologically interesting unnatural compounds.1 Compounds contain-
ing this unit can also serve as key intermediates for the preparation of
the stereoisomeric chrysanthemic acids,2 norcaradienes,3 3-oxabi-
cyclo[3.1.0]hexan-2-ones,4 and substituted cyclopropanes.5 There
are some known methods available for their preparations.6 However,
most of these methods suffer from their long synthetic routes or poor
yields.7 Thus, developing an efficient methodology for synthesis of
3-oxabicyclo[3.1.0]hexan-2-ols is highly desirable.
In our previous reports, different ring-opening reactions of ACPs
were observed under the catalysis of Pd(II), Pd(0), or Iꢀ, based on
the nature of the catalyst and reaction conditions.13 Besides the
selective cleavage of the s-bonds (proximal and distal bonds) in the
cyclopropane ring, we have also observed the iodolactonization of
the alkylidenecyclopropyl esters.14 Herein, we wish to report our
recent observation on the factors determining the diaster-
eoselectivity in the iodocyclization of alkylidenecyclopropyl
ketones with N-iodosuccinimide (NIS) to form 3-oxabicy-
clo[3.1.0]hexan-2-ols.
Alkylidenecyclopropanes (ACPs) are highly strained but readily
accessible molecules, which may serve as useful building blocks in
organic synthesis.8 ACPs readily undergo a variety of ring-opening
reactions to relief the ring strain, which comes from the copresence
of exo-cyclic double bond and the three-membered carbocycle.9
Numerous efforts have been devoted to the research in this area,
such as 1,3-dipolar cycloaddition,10 Diels–Alder reaction,11 and the
reactions via proximal or distal cleavage under the catalysis of
transition metal complexes or Lewis acids.12 Furthermore, the C–C
double bond in ACPs is also very reactive. Thus, an attractive but
troublesome feature of ACPs is their multi-reaction sites that may
lead to the formation of a variety of different products (Scheme 1).
Therefore, it is attractive to develop the reactions of ACPs, which
2. Results and discussion
Initially, the reaction of 1-(ethoxycarbonyl)-2-(octylidene)cy-
clopropyl methyl ketone (1a) with NIS was carried out in CH3CN/
H2O¼2:1 at room temperature. To our delight, the reaction
smoothly led to the formation of a diastereomeric mixture of
product 2a with a ratio of 33:67 in 73% yield (entry 1, Table 1).
When 2 equiv of I2 were used, the combined yield of 2a was only
39% (entry 2, Table 1), much inferior to the reaction of 1a with NIS.
Thus, we chose NIS as the iodocyclization reagent to optimize the
reaction conditions. As we have demonstrated the important role of
water in the reaction of alkylidenecyclopropyl carboxylic acid es-
ters with iodine or NIS,11 further screening of the solvent system
was conducted (Table 1). In most cases, the reaction proceeded
smoothly to afford moderate yields of a diastereomeric mixture of
2a in a mixed solvent of CH3CN/H2O (1:1 to 8:1 by volume) (entries
* Corresponding author.
E-mail address: masm@mail.sioc.ac.cn (S. Ma).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.06.060

8900
J. Chen et al. / Tetrahedron 64 (2008) 8899–8906
R1
R2
R
R
R1
R2
X
Y
X(Y)
Y(X)
R'
distal C-C
distal C-C
cleavage
R'
proximal
R
cleavage
R'
(2)
(1)
E
proximal
E
distal
R
R
X
Y
E
E
(3)
Y(X)
R'
proximal C-C
cleavage
proximal C-C
cleavage
R'
X(Y)
addition to
X
Y
C=C bond
(X)Y
(Y)X
R
R'
Scheme 1.
3–5, Table 1). The best results were obtained when a mixed solvent
of CH3CN/H2O (10:1) was used affording 2a in 85% yield (entry 6,
Table 1). Further studies showed that the yield decreased with
a further increased ratio of CH3CN/H2O (entry 7, Table 1). Although
there are four new chiral centers formed in the reaction, only two
all the substituents here is the same as what observed in the major
products (1S ,2R ,4S ,5R )-2a–2d, (1R ,2R ,4S ,5R )-2e, or
(1S ,2R ,4S ,5R
)-2f. With R1 being TBSOCH2CH2, the iodocyclization
products underwent further desilylation to afford (1R ,2R ,4S ,5S )-
2l and (1R ,2R ,4S ,5S )-2m (entries 6 and 7, Table 3). The stereo-
chemistry of these major products 2 was established by the X-ray
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
diastereomers, i.e., (1S
*
,2R
*
,4R
*
,5R
*
)-2a and (1S
*
,2R
*
,4S
*
,5R )-2a,
*
were formed in a ratio of 41:59 to 32:68. The difference is the
relative configuration at the 4-position. The two diastereomers can
be readily separated by column chromatography on silica gel.
With the optimized reaction conditions in hand, the scope of the
reaction was studied with the typical results summarized in Table 2.
R1 may be alkyl, Bn, or Ph; R2 may be CO2Et and COCH3; R3 may be Me
diffraction study of (1R
*
,2R
*
,4S
*
,5R
,4S
*
)-2e,15 (1S
*
,2R
*
,4S
*
,5R
*
)-2f,16
(1S ,2R ,4S ,5R
*
*
*
*
)-2g,17 and (1S
*
,2R
*
*
,5R
*
)-2h18 (Fig.1). In addition,
the stereochemistry of these minor products 2 was also established
by the X-ray diffraction study of (1S ,2R ,4R ,5R
)-2c19 (Fig. 1). The
*
*
*
*
structures of other products were tentatively assigned based on the
comparison of the chemical shift of the hydrogen atom at 4-position
in the 1H NMR spectraof 2e–2h and 2c. A conclusion may be made by
comparison of the results of Tables 2 and 3 that the diastereo-
selectivities of the reaction is determined by the nature of R1
and R2.
Furthermore, the tricyclic products 2n and 2o were formed as
the only diastereomers in 73% and 61% yields when 2-(cyclo-
hexylidene)cyclopropyl ketones 1n and 1o were submitted to the
standard reaction conditions (Scheme 2). It should be noted with
or Ph. The diastereomeric ratios of the products of (1S
and (1S ,2R ,4S ,5R )-2 do not seem to have direct correlation
with the E/Z ratios of the starting materials. Under the current
reaction conditions, (1S ,2R ,4S ,5R )-2 is more favored than
)-2. However, it is interesting to note that
,5R
)-2f was obtained when R1 is the phenyl group
,2R ,4R ,5R
* * * *
)-2
*
*
*
*
*
*
*
*
(1S ,2R ,4R ,5R
* * * *
only (1S ,2R ,4S
* * *
*
(entry6, Table 2). Withthis resultinhand, wenextstartedtolookinto
the steric effect of R2 on the diastereoselectivity of this cyclization.
In fact, we observed that the reaction of the starting materials
with R2 being bulkier substituent, such as SO2Ph and Ts, also pro-
interest that here again the same type of products (1S
and (1R ,2R ,5S )-2o were formed. The structure of the two prod-
ucts were established by the X-ray diffraction study of
(1S ,2R ,5R
)-2n (Fig. 2),20 indicating the highly selective formation
of the same type of chiral centers at 1-, 2-, and 5-positions.
*
,2R
* *
,5R )-2n
*
*
*
ceeded smoothly to afford the (1R
*
,2R
*
,4S
*
,5S )-2g–2m as the only
*
products with R1 being 1-alkyl or c-hexyl in moderate to good yields
*
*
*
(Table 3). The relative stereochemistry in terms of the orientation of
Table 1
Iodocyclization of 1-(ethoxycarbonyl)-2-(octylidene)cyclopropyl methyl ketone (1a) with NIS under different conditionsa
6
6
C7H15
H
5
5
CO2Et
OH
CO2Et
OH
I
I
CO2Et
solvent
rt
1
1
4
+
4
+
NIS
2
2
C7H15
C7H15
O
O
O
3
3
1a
(1S*, 2R*, 4R*, 5R*)-2a
(as 4R*-2a in the Table)
(1S*, 2R*, 4S*, 5R*)-2a
(as 4S*-2a in the Table)
Entry
MeCN/H2O
Time (h)
Isolated yield
of 2a (%)
4R
*
-2a/4S -2a
*
4R
*
-2a
*
4S -2a
1
2:1
2:1
1:1
4:1
8:1
0.75
0.5
6.25
5
5
3.25
2.25
24
16
26
27
23
34
23
49
23
46
45
49
51
43
33:67
41:59
36:64
38:62
32:68
40:60
35:65
2b
3
4
5
6
7
10:1
20:1
a
The reaction was carried out using 0.25–0.5 mmol of 1a and 0.3–0.6 mmol of NIS (1.2 equiv) in 1.5–3 mL of solvent at rt.
I2 (2 equiv) was used instead of NIS.
b

J. Chen et al. / Tetrahedron 64 (2008) 8899–8906
8901
Table 2
Iodocyclization of alkylidenecyclopropyl ketones 1 with NISa
R1
6
6
R2
5
R2
5
R2
R3
I
I
CH3CN:H2O = 10:1
rt
1
1
4
H
+
+
NIS
4
2
2
OH
R3
R1
OH
R3
R1
O
O
O
3
3
(1S*, 2R*, 4R*, 5R*)-2
(as 4R*-2 in the Table)
(1S*, 2R*, 4S*, 5R*)-2
(as 4S*-2 in the Table)
1
Entry
1
E/Z ratio of 1
Time (h)
Yield of 4R
*
-2 (%)
Yield of 4S
*
-2 (%)
R1
R2
R3
1
2
C7H15
C4H9
Bn
C7H15
C7H15
Ph
CO2Et
CO2Et
CO2Et
CO2Et
COMe
CO2Et
Me (1a)
Me (1b)
Me (1c)
Ph (1d)
Me (1e)
Me (1f)
2.5:1
2.1:1
1:1
3
3
12
4
2
2
34 (4R
*
-2a)
-2b)
-2c)
51 (4S -2a)
*
22 (4R
*
54 (4S
43 (4S
67 (4S
*
*
*
-2b)
-2c)
-2d)
3
21 (4R
*
4b
5
d
17 (4R
21 (4R
d
*
-2d)
-2e)c
2.5:1
100:0
*
51 (4S
*
-2e)c
-2f)
6
76 (4S
*
a
The reaction was carried out using 0.25–0.5 mmol of 1 and 1.2 equiv of NIS in 1.5–3 mL of the mixed solvent (CH3CN/H2O¼10:1) at rt.
E/Z ratio of 1 is not detected.
b
c
According to the sequence rule, the relative configuration of the chiral center at 1-position in 2e should be read as R .
*
A possible mechanism for this iodocyclization reaction is
moderate to good yields. The stereoselectivity of the products
might be influenced by the steric effects of the substituent group R1
and R2 of the starting materials. With R1 being phenyl or R2 being
bulkier substituents, such as SO2Ph and Ts, only the
depicted in Scheme 3. Firstly, electrophilic interaction of Iþ with the
C]C bond would form the intermediate 3, which would undergo
a ring-opening reaction to generate a carbocationic intermediate
3A. Due to the steric interaction between group R1 and I, the sub-
sequent intramolecular nucleophilic attack of the carbonyl oxygen
at the positively charged carbon center would lead to the formation
of the intermediate 4C as the major or only diastereomer. Sub-
sequent stereoselective attack of 4B or 4C by water could finally
lead to the formation of different diastereomer of product 2,
depending on the steric bulkiness of R1 and R2 groups.
(1S
*
,2R
*
,4S
*
,5R
*
)-2f or (1R
*
,2R
*
,4S
*
,5S )-2g–2m were obtained. In
*
this reaction, H2O may act as a nucleophile, leading to the gener-
ation of hydroxyl group in the product. Further investigations in
this area are being carried out in our laboratory.
4. Experimental section
4.1. Synthesis of alkylidenecyclopropyl ketones (1a–1o)
3. Conclusion
Alkylidenecyclopropyl ketones 1a–1e, 1g–h, and 1n used in this
study were easily prepared via the Rh2(OAc)4-catalyzed cyclo-
propanation of the corresponding 1,2-allenes21 with the corre-
sponding diazo compounds22 according to known procedure.23,13b
In conclusion, we have developed an iodocyclization reaction of
alkylidenecyclopropyl ketones with NIS under aqueous conditions
leading to the formation of 3-oxabicyclo[3.1.0]hexan-2-ols in
Table 3
4.1.1. 1-(Ethoxycarbonyl)-2-(benzylidene)cyclopropyl methyl
ketone (E-1f)
Iodocyclization of alkylidenecyclopropyl ketones 1 with NISa
R1
6
A solution of 2-diazo-3-oxobutyric acid ethyl ester 6a (935 mg,
6 mmol) in 10 mL of CH2Cl2 was added with a syringe to a solution
of phenylpropadiene (2.162 g, 19 mmol) and Rh2(OAc)4 (7 mg,
0.016 mmol) in 5 mL of CH2Cl2 under reflux. After the addition was
over, the mixture was stirred for 5 h under reflux. Evaporation and
chromatography on silica gel (eluent: petroleum ether; petroleum
ether/Et2O¼20:1) gave E-1f (418 mg, 29%) as a liquid. 1H NMR
R2
5
R2
I
CH3CN:H2O = 10:1
rt
1
H
+
NIS
4
2
OH
R1
O
O
3
1
(1R*, 2R*, 4S*, 5S*)-2
Entry
1
Time (h)
Yield of (1R
*
,2R
*
,4S
*
*
,5S )-2 (%)
R1
R2
(300 MHz, CDCl3)
d
7.51 (d, J¼7.2 Hz, 2H), 7.36 (t, J¼6.6 Hz, 2H), 7.28
(t, J¼6.6 Hz, 1H), 6.86 (t, J¼2.7 Hz, 1H), 4.27–4.16 (m, 2H), 2.54 (dd,
1
2
C4H9
SO2Ph (1g)
SO2Ph (1h)
SO2Ph (1i)
Ts (1j)
SO2Ph (1k)
SO2Ph (1l)
Ts (1m)
15
14.5
85
40
36
11
83 (2g)
80 (2h)
71 (2i)
J¼2.7, 9.6 Hz, 1H), 2.47 (dd, J¼2.7, 9.6 Hz, 1H), 2.39 (s, 3H), 1.27 (t,
C7H15
C8H15
C7H15
c-Hexyl
TBSOCH2CH2
TBSOCH2CH2
3b
4c
5c
6c
7c
J¼6.9 Hz, 3H); 13C NMR (75.4 MHz, CDCl3)
d 200.1, 168.8, 135.5,
62 (2j)
128.6,128.1,127.3, 124.0, 119.1, 61.6, 37.8, 28.2,18.7, 14.0; MS (EI) m/z
244 (Mþ, 34.77), 215 (69.44), 199 (64.62), 43 (100); IR (neat) 1709,
1600, 1454, 1292, 1257 cmꢀ1; HRMS (EI) calcd for C15H16Oþ3 (Mþ):
244.1099. Found: 244.1106. The stereochemistry of this product
was determined by the 1H–1H NOESY spectra (300 MHz).
65 (2k)
83 (2l)d
68 (2m)d
11
a
The reaction was carried out using 0.1–0.5 mmol of 1 and 1.2 equiv of NIS in 1.5–
3 mL of solvent at rt.
b
NIS (1.7 equiv) was used.
NIS (1.5 equiv) was used.
The iodocyclization products underwent subsequent desilylation to afford 2l
c
4.1.2. 1-(Phenylsulfonyl)-2-(nonylidene)cyclopropyl methyl ketone
(E-1i)
d
and 2m.
The reaction of 1-(phenylsulfonyl)-1-diazopropan-2-one 6b
(672 mg, 3.0 mmol) with undeca-1,2-diene (3.38 g, 22 mmol) and
Rh2(OAc)4 (5 mg, 0.01 mmol) in CH2Cl2 (15 mL) afforded E-1i
Ts
OH
SO2Ph
OH
I
I
HO
HO
(132 mg, 13%) as a liquid. 1H NMR (300 MHz, CDCl3)
d
7.98 (d,
O
O
(1R*, 2R*, 4S*, 5S*)-2m
(1R*, 2R*, 4S*, 5S*)-2l
J¼7.8 Hz, 2H), 7.63 (t, J¼7.5 Hz, 1H), 7.53 (t, J¼7.8 Hz, 2H), 6.14–6.07

8902
J. Chen et al. / Tetrahedron 64 (2008) 8899–8906
6
1
5
I
CO2Et
OH
NIS (1.2 equiv)
CO2Et
2
4
O
CH3CN:H2O = 10:1
rt, 73%
3
O
(1S*, 2R*, 5R*)-2n
1n
6
1
5
I
SO2Ph
OH
NIS (1.2 equiv)
2
4
SO2Ph
O
CH3CN:H2O = 10:1
rt, 12h
3
O
1o
(1R*, 2R*, 5S*)-2o
Scheme 2.
Figure 2. ORTEP representation of 2n.
d
7.84 (d, J¼8.4 Hz, 2H), 7.30 (d, J¼8.4 Hz, 2H), 6.11–6.07 (m, 1H),
2.63–2.59 (m,1H), 2.42 (s, 3H), 2.30–2.25 (m, 3H), 2.07 (s, 3H),1.52–
1.47 (m, 2H), 1.29–1.28 (m, 8H), 0.87 (t, J¼6.0 Hz, 3H); 13C NMR
(75.4 MHz, CDCl3)
d 197.0, 144.6, 136.2, 129.3, 129.2, 124.9, 118.5,
53.7, 31.7, 31.3, 29.04, 28.96, 28.3, 26.4, 22.5, 21.6, 17.4, 14.0; MS (EI)
m/z 348 (Mþ, 0.67), 263 (12.28), 43 (100); IR (neat) 2927, 1706, 1597,
1319, 1156 cmꢀ1; HRMS (EI) calcd for C20H28O3Sþ (Mþ): 348.1759.
Found: 348.1754. The stereochemistry of this product was de-
termined by the 1H–1H NOESY spectra (300 MHz).
4.1.4. 1-(Phenylsulfonyl)-2-(cyclohexylmethylene)cyclopropyl
methyl ketone (E-1k)
The reaction of 1-(phenylsulfonyl)-1-diazopropan-2-one 6b
(770 mg, 3.4 mmol) with propa-1,2-dienylcyclohexane (4.4 g,
36 mmol) and Rh2(OAc)4 (7 mg, 0.016 mmol) in CH2Cl2 (15 mL)
afforded E-1k (255 mg, 23%) as a liquid. 1H NMR (300 MHz, CDCl3)
d
7.97 (d, J¼7.5 Hz, 2H), 7.62 (t, J¼7.5 Hz, 1H), 7.52 (t, J¼7.8 Hz, 2H),
6.01 (dt, J¼2.7, 6.3 Hz, 1H), 2.72–2.67 (m, 1H), 2.38–2.33 (m, 2H),
2.07 (s, 3H), 1.86–1.65 (m, 6H),1.37–1.16 (m, 4H); 13C NMR
(75.4 MHz, CDCl3)
d 197.0,139.1,133.6,129.9,129.2,128.7,117.0, 52.7,
39.9, 31.9, 31.8, 26.3, 25.9, 25.6, 18.0; MS (EI) m/z 318 (Mþ, 1.86), 236
(24.03), 43 (100); IR (neat) 2926, 1704, 1585, 1447, 1318, 1157 cmꢀ1
,
HRMS (EI) calcd for C18H22O3Sþ (Mþ): 318.1290. Found: 318.1276.
Figure 1. ORTEP representations of 2e–2h and 2c.
(m, 1H), 2.68–2.64 (m, 1H), 2.33–2.27 (m, 3H), 2.08 (s, 3H), 1.54–
4.1.5. 1-(Phenylsulfonyl)-2-((2-tert-butyldimethyloxysilane)-
amylidene)cyclopropyl methyl ketone (E-1l)
The reaction of 1-(phenylsulfonyl)-1-diazopropan-2-one 6b
(670 mg, 3 mmol) with 5-tert-butyldimethylsiloxylpenta-1,2-diene
(1.828 g, 9 mmol) and Rh2(OAc)4 (8þ8 mg, 0.036 mmol) in CH2Cl2
(10 mL) afforded E-1l (221 mg, 19%) as a liquid. 1H NMR (300 MHz,
1.46 (m, 2H), 1.35–1.27 (m, 10H), 0.88 (t, J¼6.3 Hz, 3H); 13C NMR
(75.4 MHz, CDCl3)
d
196.9, 139.2, 133.6, 129.1, 128.6, 125.2, 118.3,
53.6, 31.7, 31.3, 29.2, 29.14, 29.08, 28.2, 26.3, 22.5, 17.5, 14.0; MS (EI)
m/z 348 (Mþ, 2.46), 249 (56.33), 43 (100); IR (neat) 2927,1706,1568,
1447, 1320, 1157 cmꢀ1; HRMS (EI) calcd for C20H28O3Sþ (MþNaþ):
348.1759. Found: 348.1765.
CDCl3)
d
7.97 (d, J¼7.2 Hz, 2H), 7.62 (t, J¼7.5 Hz, 1H), 7.51 (t,
J¼7.8 Hz, 2H), 6.17–6.12 (m, 1H), 3.80–3.72 (m, 2H), 2.68–2.64 (m,
4.1.3. 1-(p-Methylphenylsulfonyl)-2-(octylidene)cyclopropyl methyl
ketone (E-1j)
1H), 2.54–2.48 (m, 2H), 2.34–2.29 (m, 1H), 2.05 (s, 3H), 0.87 (s, 9H),
0.04 (s, 6H); 13C NMR (75.4 MHz, CDCl3)
d 196.8, 139.2, 133.6, 129.1,
The reaction of 1-(p-methylbenzenesulfonyl)-1-diazopropan-2-
one 6c (951 mg, 4 mmol) with deca-1,2-diene (2.007 g,
0.145 mmol) and Rh2(OAc)4 (5 mg, 0.011 mmol) in CH2Cl2 (15 mL)
afforded E-1j (209 mg, 15%) as a liquid. 1H NMR (300 MHz, CDCl3)
128.7, 122.1, 119.9, 61.6, 53.8, 34.9, 26.3, 25.8, 18.2, 17.3, ꢀ5.4; MS
(ESI) m/z 395 (MþHþ); IR (neat) 2954, 1705, 1568, 1320, 1447, 1157,
1098 cmꢀ1
;
HRMS (ESI) calcd for C20H30NaO4SSiþ (MþNaþ):
417.1526. Found: 417.1522.

J. Chen et al. / Tetrahedron 64 (2008) 8899–8906
8903
R1
R1
H
R1
H
I
I
I+
R2
R3
R2
R3
5
4
R2
R3
H
O
O
O
3A
3
1
R2
R3
I
R2
R3
I
R1
H
O
O
R1
H
4B
4C
H2O
H2O
I
R2
I
R2
R3
H
R3
R1
O
O
R1
OH
OH
H
major
minor
Scheme 3.
4.1.6. 1-(p-Methylphenylsulfonyl)-2-((2-tert-butyldimethyl-
oxysilane)amylidene)-cyclopropyl methyl ketone (E-1m)
4.2.1.1. (1S
*
,2R
*
,4R
*
,5R
*
)-1-(Ethoxycarbonyl)-2-methyl-4-heptyl-5-
,2R ,4R ,5R
)-2a). Oil. 1H
5.01 (s, 1H), 4.38–4.21 (m, 2H), 3.98 (dd,
iodo-3-oxabicyclo[3.1.0]hexan-2-ol ((1S
NMR (300 MHz, CDCl3)
*
*
*
*
The reaction of 1-(p-methylbenzenesulfonyl)-1-diazopropan-
2-one 6c (721 mg, 3 mmol) with 5-tert-butyldimethylsilox-
ylpenta-1,2-diene (1.786 g, 9 mmol) and Rh2(OAc)4 (8 mg,
0.018 mmol) in CH2Cl2 (10 mL) afforded E-1m (143 mg, 12%) as
d
J¼11.1, 4.2 Hz, 1H), 1.91–1.80 (m, 2H), 1.83 (d, J¼5.4 Hz, 1H), 1.58–
1.55 (m, 2H),1.46 (s, 3H),1.45 (d, J¼5.4 Hz,1H),1.35 (t, J¼7.2 Hz, 3H),
1.29–1.26 (m, 8H), 0.86 (t, J¼6.0 Hz, 3H); 13C NMR (75.4 MHz,
a liquid. 1H NMR (300 MHz, CDCl3)
(t, J¼7.8 Hz, 2H), 6.17–6.11 (m, 1H), 3.80–3.72 (m, 2H), 2.65–2.61
(m, 1H), 2.54–2.48 (m, 2H), 2.43 (s, 3H), 2.31–2.27 (m, 1H), 2.08
(s, 3H), 0.88 (s, 9H), 0.05 (s, 6H); 13C NMR (75.4 MHz, CDCl3)
d
7.85 (d, J¼8.7 Hz, 2H), 7.32
CDCl3) d 170.1, 103.3, 84.7, 62.1, 42.4, 37.8, 31.8, 29.27, 29.26, 27.1,
26.8, 24.3, 22.6, 14.2, 14.1, 12.9; MS (ESI) m/z 433 (MþNaþ), 393
(MþHþ)ꢀH2O; IR (neat) 3467, 2926, 1722 (sh), 1699, 1466, 1376,
1080, 1210 cmꢀ1; HRMS (MALDI) calcd for C16H27O4INaþ (MþNaþ):
433.0846. Found: 433.0846.
d
196.9, 144.7, 136.2, 129.4, 129.2, 121.9, 120.1, 61.7, 54.0,
34.9, 26.5, 25.8, 21.6, 18.2, 17.3, ꢀ5.4; MS (ESI) m/z 409 (MþHþ);
IR (neat) 2954, 1706, 1599, 1470, 1319, 1157, 1095 cmꢀ1; HRMS
(ESI) calcd for
431.1674.
4.2.1.2. (1S
iodo-3-oxabicyclo[3.1.0]hexan-2-ol ((1S
NMR (300 MHz, CDCl3) 4.97 (s, 1H), 4.41–4.19 (m, 3H), 1.84–1.75
(m, 1H), 1.71 (d, J¼6.3 Hz, 1H), 1.54–1.20 (m, 18H), 0.86 (t, J¼6.0 Hz,
3H); 13C NMR (75.4 MHz, CDCl3)
170.1, 102.6, 84.2, 62.0, 41.7, 31.7,
*
,2R
*
,4S
*
,5R
*
)-1-(Ethoxycarbonyl)-2-methyl-4-heptyl-5-
C
21H32NaO4SSiþ (MþNaþ): 431.1683. Found:
*
,2R ,4S ,5R
*
*
*
)-2a). Oil. 1H
d
4.1.7. 1-(Phenylsulfonyl)-2-(cyclohexylidene)cyclopropyl methyl
ketone (1o)
The reaction of 1-(phenylsulfonyl)-1-diazopropan-2-one 6b
(1.796 g, 8 mmol) with vinylidenecyclohexane (3.439 g, 32 mmol)
and Rh2(OAc)4 (20 mgþ17 mg, 0.086 mmol) afforded 1o (0.824 g,
34%) as a solid, mp 93–94 ꢁC (Et2O/petroleum ether). 1H NMR
d
29.63, 29.60, 29.1, 26.2, 23.4, 22.8, 22.6, 14.3, 14.1, 12.8; MS (ESI) m/z
433 (MþNaþ), 393 (MþHþ)ꢀH2O; IR (neat) 3468, 2928, 1722, 1699,
1376, 1211 cmꢀ1; HRMS (MALDI) calcd for C16H27O4INaþ (MþNaþ):
433.0846. Found: 433.0836.
(300 MHz, CDCl3)
d
8.01 (d, J¼7.2 Hz, 2H), 7.61 (t, J¼7.8 Hz, 1H), 7.52
4.2.2. (1S
*
,2R
*
,5R )-1-(Ethoxycarbonyl)-2-methyl-4-butyl-5-iodo-
*
(t, J¼7.8 Hz, 2H), 2.61 (d, J¼8.7 Hz, 1H), 2.39–2.35 (m, 2H), 2.26 (d,
3-oxabicyclo[3.1.0]hexan-2-ol (2b)
Thereactionof1b(113 mg, 0.5 mmol)andNIS(135 mg, 0.6 mmol)
in 2 mL of CH3CN and 0.2 mL of H2O afforded (1S
J¼9.0 Hz, 1H), 2.19–2.09 (m, 2H), 2.04 (s, 3H), 1.73–1.45 (m, 6H); 13
C
NMR (75.4 MHz, CDCl3)
d
197.8, 139.7, 137.7, 133.5, 129.3, 128.6,
*
,2R
*
,4R
*
,5R )-2b
*
109.8, 54.9, 33.6, 33.5, 27.3, 27.1, 26.1, 25.8, 18.4; MS (EI) m/z 304
(0.97, Mþ), 262 (9.44), 43 (100); IR (neat) 2934, 1702, 1568, 1447,
1308,1150 cmꢀ1. Anal. Calcd for C17H20O3S: C, 67.08; H, 6.62. Found:
C, 67.18; H, 6.62.
(40 mg, 22%) and (1S ,2R ,4S ,5R )-2b (99 mg, 54%).
*
*
*
*
4.2.2.1. (1S
iodo-3-oxabicyclo[3.1.0]hexan-2-ol ((1S
NMR (300 MHz, CDCl3) 5.00 (s, 1H), 4.37–4.20 (m, 2H), 3.97 (dd,
*
,2R
*
,4R
*
,5R
*
)-1-(Ethoxycarbonyl)-2-methyl-4-butyl-5-
*
,2R ,4R ,5R
*
*
*
)-2b). Oil. 1H
d
J¼11.1, 3.9 Hz, 1H), 1.93–1.81 (m, 2H), 1.82 (d, J¼5.7 Hz, 1H), 1.59–
4.2. Typical procedure for iodocyclization of
alkylidenecyclopropyl ketones with NIS
1.51 (m, 1H), 1.48–1.44 (m, 4H), 1.40–1.23 (m, 6H), 0.89 (t, J¼6.9 Hz,
3H); 13C NMR (75.4 MHz, CDCl3)
d 170.0, 103.3, 84.7, 62.1, 42.4, 37.5,
28.9, 27.1, 24.3, 22.3, 14.2, 14.0, 12.8; MS (ESI) m/z 391 (MþNaþ), 351
(MþHþ)ꢀH2O; IR (neat) 3457, 2956, 1722 (sh), 1697, 1376,
1209 cmꢀ1; HRMS (MALDI) calcd for C13H21O4INaþ (MþNaþ):
391.0377. Found: 391.0393.
4.2.1. Synthesis of (1S
*
,2R
*
,5R )-1-(ethoxycarbonyl)-2-methyl-4-
*
heptyl-5-iodo-3-oxabicyclo[3.1.0]hexan-2-ol (2a)
A solution of 1a (68 mg, 0.25 mmol) and NIS (68 mg, 0.3 mmol)
in 1 mL of CH3CN and 0.1 mL of H2O was stirred in a flask for 3.25 h
at room temperature as monitored by TLC. The reaction was
quenched with a saturated aqueous Na2S2O3 solution, extracted
with ether, and dried over anhydrous MgSO4. Evaporation and
column chromatography on silica gel (eluent: petroleum ether/
4.2.2.2. (1S
iodo-3-oxabicyclo[3.1.0]hexan-2-ol ((1S
NMR (300 MHz, CDCl3) 4.96 (s, 1H), 4.40–4.18 (m, 3H), 1.81–1.77
(m, 1H), 1.69 (d, J¼6.0 Hz, 1H), 1.49–1.27 (m, 12H), 0.88 (t, J¼6.9 Hz,
*
,2R
*
,4S
*
,5R
*
)-1-(Ethoxycarbonyl)-2-methyl-4-butyl-5-
*
,2R ,4S ,5R
*
*
*
)-2b). Oil. 1H
d
Et2O¼8:1) afforded (1S
*
,2R
*
,4R
*
,5R
*
)-2a (35 mg, 34%) and
3H); 13C NMR (75.4 MHz, CDCl3)
d 170.0, 102.6, 84.1, 61.9, 41.7, 29.3,
(1S ,2R ,4S ,5R )-2a (52 mg, 51%).
*
*
*
*
28.3, 23.3, 22.8, 22.7,14.2,13.9,12.8; MS (ESI) m/z 391 (MþNaþ), 351

8904
J. Chen et al. / Tetrahedron 64 (2008) 8899–8906
(MþHþ)ꢀH2O; IR (neat) 3469, 2935, 1722, 1698, 1376, 1208 cmꢀ1
;
(1R
*
,2R
,4R
* *
,5R
*
)-2e (40 mg, 21%) and (1R
*
,2R
*
,4S
*
,5R )-2e (97 mg,
*
HRMS (MALDI) calcd for C13H21O4INaþ (MþNaþ): 391.0377. Found:
51%).
391.0377.
4.2.5.1. (1R
*
,2R
*
,4R
*
,5R
*
)-1-Acetyl-2-methyl-4-heptyl-5-iodo-3-oxa-
,2R ,4R ,5R
)-2e). Oil. 1H NMR (300 MHz,
4.2.3. (1S
*
,2R
*
,5R
*
)-1-(Ethoxycarbonyl)-2-methyl-4-benzyl-5-iodo-
bicyclo[3.1.0]-hexan-2-ol((1R
*
*
*
*
3-oxabicyclo[3.1.0]hexan-2-ol (2c)
Thereactionof1c(130 mg, 0.5 mmol)andNIS(135 mg, 0.6 mmol)
in 2 mL of CH3CN and 0.2 mL of H2O afforded (1S
CDCl3)
d
4.39 (s, 1H), 3.98 (dd, J¼11.1, 3.6 Hz, 1H), 2.39 (s, 3H), 1.92–
1.73 (m, 2H), 1.77 (d, J¼5.7 Hz, 1H), 1.63–1.40 (m, 1H), 1.53 (d,
J¼6.6 Hz, 1H), 1.45 (s, 3H), 1.40–1.26 (m, 9H), 0.86 (t, J¼6.0 Hz, 3H);
*
,2R
*
,4R
*
,5R )-2c
*
(42 mg, 21%) and (1S ,2R ,4S ,5R )-2c (87 mg, 43%).
*
*
*
*
13C NMR (75.4 MHz, CDCl3)
d 205.6, 104.0, 84.5, 48.5, 37.6, 31.8, 29.6,
29.3, 29.2, 27.8, 26.8, 24.6, 22.6, 14.1, 13.3; MS (ESI) m/z 403 (MþNaþ),
4.2.3.1. (1S
iodo-3-oxabicyclo[3.1.0]hexan-2-ol ((1S
NMR (300 MHz, CDCl3) 7.36–7.21 (m, 5H), 5.17 (s, 1H), 4.43–4.20
*
,2R
*
,4R
*
,5R
*
)-1-(Ethoxycarbonyl)-2-methyl-4-benzyl-5-
363 (MþHþ)ꢀH2O; IR (neat) 3435, 2925, 1679, 1456, 1363,
*
,2R ,4R ,5R
*
*
*
)-2c). Oil. 1H
1192 cmꢀ1
;
HRMS calcd for C15H25O3INaþ (MþNaþ): 403.0741.
d
Found: 403.0751.
(m, 3H), 3.35 (dd, J¼13.5, 3.0 Hz, 1H), 3.21 (dd, J¼13.5, 11.1 Hz, 1H),
1.89 (d, J¼5.7 Hz, 1H), 1.48 (d, J¼5.7 Hz, 1H), 1.47 (s, 3H), 1.39 (t,
4.2.5.2. (1R
bicyclo[3.1.0]-hexan-2-ol ((1R
(petroleum ether/ether). 1H NMR (300 MHz, CDCl3)
*
,2R
*
,4S
*
,5R
*
)-1-Acetyl-2-methyl-4-heptyl-5-iodo-3-oxa-
,2R ,4S ,5R
)-2e). Solid, mp 55–58 ꢁC
4.65 (s, 1H),
J¼5.7 Hz, 3H); 13C NMR (75.4 MHz, CDCl3)
d
170.0, 138.9, 129.8,
*
*
*
*
128.2, 126.2, 103.6, 85.4, 62.2, 43.6, 42.7, 27.2, 24.4, 14.2, 11.8; MS
d
(ESI) m/z 425 (MþNaþ), 385 (MþHþ)-H2O; IR (neat) 3457, 2985,
4.36 (m, 1H), 2.34 (s, 3H), 1.88–1.75 (m, 1H), 1.67 (d, J¼6.3 Hz, 1H),
1720 (sh), 1696, 1377, 1214 cmꢀ1
C
; HRMS (MALDI) calcd for
1.48 (d, J¼6.3 Hz, 1H), 1.44 (s, 3H), 1.40–1.25 (m, 11H), 0.85 (t,
16H19O4INaþ (MþNaþ): 425.0220. Found: 425.0214.
J¼6.6 Hz, 3H); 13C NMR (75.4 MHz, CDCl3)
d 205.8, 103.3, 83.9, 48.0,
31.7, 29.55, 29.53, 29.2, 29.1, 26.2, 23.7, 23.5, 22.6,14.1,13.8; MS (ESI)
4.2.3.2. (1S
iodo-3-oxabicyclo[3.1.0]hexan-2-ol ((1S
NMR (300 MHz, CDCl3) 7.29–7.21 (m, 5H), 4.95 (s, 1H), 4.70 (dd,
*
,2R
*
,4S
*
,5R
*
)-1-(Ethoxycarbonyl)-2-methyl-4-benzyl-5-
m/z 403 (MþNaþ), 363 (MþHþ)ꢀH2O; IR (neat) 3418, 2927, 1674,
*
,2R ,4S ,5R
*
*
*
)-2c). Oil. 1H
1363, 1199 cmꢀ1
;
HRMS calcd for C15H25O3INaþ (MþNaþ):
d
403.0741. Found: 403.0744.
J¼7.5, 3.0 Hz, 1H), 4.36–4.19 (m, 2H), 3.13 (dd, J¼14.7, 3.0 Hz, 1H),
2.84 (dd, J¼14.1, 7.2 Hz, 1H), 1.65 (d, J¼6.0 Hz, 1H), 1.45 (s, 3H), 1.33
(t, J¼7.5 Hz, 3H), 1.25 (d, J¼6.3 Hz, 1H); 13C NMR (75.4 MHz, CDCl3)
4.2.6. (1S
*
,2R
*
,4S
*
,5R
*
)-1-(Ethoxycarbonyl)-4-phenyl-5-iodo-3-
,2R ,4S ,5R )-2f)
oxabicyclo[3.1.0]hexan-2-one ((1S
The reaction of 1f (122 mg, 0.5 mmol) and NIS (135 mg,
0.6 mmol) in 2 mL of CH3CN and 0.2 mL of H2O afforded
*
*
*
*
d
169.9, 137.0, 129.5, 128.1, 126.4, 102.7, 84.1, 61.9, 41.2, 35.5, 23.2,
22.8, 14.2, 11.9; MS (ESI) m/z 425 (MþNaþ), 385 (MþHþ)ꢀH2O; IR
(neat) 3464, 2985, 1720, 1697, 1376, 1213 cmꢀ1; HRMS (MALDI)
calcd for C16H19O4INaþ (MþNaþ): 425.0220. Found: 425.0225.
(1S
*
,2R
*
,4S
*
,5R
)-2f (148 mg, 76%) as a solid, mp 108–110 ꢁC (pe-
*
troleum ether/ether). 1H NMR (300 MHz, CDCl3)
d
7.50–7.47 (m,
2H), 7.40–7.36 (m, 3H), 5.53 (s, 1H), 5.19 (s, 1H), 4.41–4.25 (m, 2H),
4.2.4. (1S
*
,2R
*
,5R
*
)-1-(Ethoxycarbonyl)-2-phenyl-4-heptyl-5-iodo-
1.79 (d, J¼6.3 Hz, 1H), 1.76 (d, J¼6.3 Hz, 1H), 1.60 (s, 3H), 1.37 (t,
3-oxabicyclo[3.1.0]hexan-2-ol (2d)
Thereactionof1d(165 mg, 0.5 mmol)andNIS(135 mg, 0.6 mmol)
in 2 mL of CH3CN and 0.2 mL of H2O afforded (1S
J¼7.2 Hz, 3H); 13C NMR (75.4 MHz, CDCl3)
d 169.9, 135.0, 128.6,
128.2, 127.4, 103.0. 84.8, 62.1, 42.2, 23.3, 22.4, 14.2, 13.6; MS (ESI)
m/z 411 (MþNaþ), 371 (MþHþ)ꢀH2O; IR (neat) 3453, 2984, 1719,
1696, 1376, 1214 cmꢀ1. Anal. Calcd for C15H17O4I: C, 46.71; H, 4.41.
Found: C, 46.40; H, 4.39.
*
,2R
*
,4R
*
,5R )-2d
*
(41 mg, 17%) and (1S ,2R ,4S ,5R )-2d (157 mg, 67%).
*
*
*
*
4.2.4.1. (1S
iodo-3-oxabicyclo[3.1.0]hexan-2-ol ((1S
NMR (300 MHz, CDCl3) 7.51–7.48 (m, 2H), 7.35–7.30 (m, 3H), 6.15
*
,2R
*
,4R
*
,5R
*
)-1-(Ethoxycarbonyl)-2-phenyl-4-heptyl-5-
*
,2R ,4R ,5R
*
*
*
)-2d). Oil. 1H
4.2.7. (1R
*
,2R
*
,4S
*
,5S
*
)-1-Phenylsulfonyl-2-methyl-4-butyl-5-iodo-
,2R ,4S ,5S )-2g)
d
3-oxabicyclo[3.1.0]hexan-2-ol ((1R
*
*
*
*
(s, 1H), 4.39–4.21 (m, 3H), 2.04–1.96 (m, 2H), 1.86 (d, J¼6.3 Hz, 1H),
1.68–1.63 (m, 2H), 1.55 (d, J¼6.6 Hz, 1H), 1.36 (t, J¼6.3 Hz, 3H), 1.45–
1.26 (m, 8H), 0.88 (t, J¼6.6 Hz, 3H); 13C NMR (75.4 MHz, CDCl3)
The reaction of 1g (144 mg, 0.5 mmol) and NIS (135 mg,
0.6 mmol) in 2 mL of CH3CN and 0.2 mL of H2O afforded
(1R
*
,2R
*
,4S
*
,5S
)-2g (180 mg, 83%) as a solid, mp 123–126 ꢁC (Et2O/
*
d
170.3, 141.0, 128.4, 128.1, 125.7, 103.9, 85.1, 62.3, 43.4, 38.2, 31.9,
hexane). 1H NMR (300 MHz, CDCl3)
d
8.06 (d, J¼7.5 Hz, 2H), 7.66 (t,
29.32, 29.27, 26.9, 26.8, 22.6, 14.2, 14.1, 13.1; MS (ESI) m/z 495
(MþNaþ), 455 (MþHþ)ꢀH2O; IR (neat) 3428, 2925, 1735, 1697,
J¼6.9 Hz, 1H), 7.54 (d, J¼6.9 Hz, 2H), 4.22 (d, J¼7.2 Hz, 1H), 3.75 (s,
1H), 2.11 (d, J¼6.6 Hz, 1H), 1.91–1.85 (m, 1H), 1.56 (d, J¼6.3 Hz, 1H),
1.43–1.24 (m, 5H), 1.02 (s, 3H), 0.87 (t, J¼5.4 Hz, 3H); 13C NMR
1600, 1449, 1375, 1177 cmꢀ1
C
;
HRMS (MALDI) calcd for
21H29O4INaþ (MþNaþ): 495.1003. Found: 495.1000.
(75.4 MHz, CDCl3) d 138.9, 134.1, 129.8, 128.8, 102.6, 82.3, 55.1, 28.7,
28.0, 23.4, 22.6, 22.5, 13.8, 8.4; MS (ESI) m/z 459 (MþNaþ), 419
4.2.4.2. (1S
iodo-3-oxabicyclo[3.1.0]hexan-2-ol ((1S
NMR (300 MHz, CDCl3) 7.53–7.50 (m, 2H), 7.36–7.32 (m, 3H), 6.11
*
,2R
*
,4S
*
,5R
*
)-1-(Ethoxycarbonyl)-2-phenyl-4-heptyl-5-
(MþHþ)ꢀH2O; IR (neat) 3471, 2933, 1447, 1391, 1307, 1151 cmꢀ1
.
*
,2R ,4S ,5R
*
*
*
)-2d). Oil. 1H
Anal. Calcd for C16H21O4SI: C, 44.05; H, 4.85. Found: C, 44.29; H, 4.70.
d
(s, 1H), 4.64 (dd, J¼8.4, 2.4 Hz, 1H), 4.38–4.20 (m, 2H), 1.95–1.88 (m,
4.2.8. (1R
*
,2R
*
,4S
*
,5S
*
)-1-Phenylsulfonyl-2-methyl-4-heptyl-5-
,2R ,4S ,5S )-2h)
1H), 1.78 (d, J¼6.3 Hz, 1H), 1.64–1.48 (m, 4H), 1.41–1.25 (m, 11H),
iodo-3-oxabicyclo[3.1.0]hexan-2-ol ((1R
The reaction of 1h (167 mg, 0.5 mmol) and NIS (136 mg,
0.6 mmol) in 2 mL of CH3CN and 0.2 mL of H2O afforded
*
*
*
*
0.89 (t, J¼6.3 Hz, 3H); 13C NMR (75.4 MHz, CDCl3)
d
170.3, 140.0,
128.5, 128.1, 125.6, 103.2, 84.6, 62.2, 42.7, 31.7, 29.64, 29.58, 29.1,
26.2, 22.6, 22.5, 14.2, 14.1, 12.7; MS (ESI) m/z 495 (MþNaþ), 455
(MþHþ)ꢀH2O; IR (neat) 3433, 2928, 1735 (sh), 1696, 1449, 1375,
1174 cmꢀ1; HRMS (MALDI) calcd for C21H29O4INaþ (MþNaþ):
495.1003. Found: 495.1012.
(1R
*
,2R
*
,4S
*
,5S
)-2h (151 mg, 80%) as a solid, mp 85–87 ꢁC (ether/
*
hexane). 1H NMR (300 MHz, CDCl3)
d
8.06 (d, J¼8.1 Hz, 2H), 7.67 (t,
J¼5.4 Hz,1H), 7.54 (t, J¼8.1 Hz, 2H), 4.23–4.21 (m,1H), 3.66 (br s,1H),
2.10 (d, J¼6.6 Hz, 1H), 1.90–1.83 (m, 1H), 1.56 (d, J¼6.0 Hz, 1H), 1.47–
1.16 (m, 11H), 1.02 (s, 3H), 0.84 (m, 3H); 13C NMR (75.4 MHz, CDCl3)
4.2.5. (1R
*
,2R
*
,5R
*
)-1-Acetyl-2-methyl-4-heptyl-5-iodo-3-
d 138.9,134.1,129.8,128.8,102.6, 82.3, 55.1, 31.7, 29.4, 29.1, 29.0, 25.9,
oxabicyclo[3.1.0]-hexan-2-ol (2e)
The reaction of 1e (119 mg, 0.5 mmol) and NIS (135 mg,
0.6 mmol) in 2 mL of CH3CN and 0.2 mL of H2O afforded
23.4, 22.6, 22.5, 14.0, 8.4; MS (ESI) m/z 501 (MþNaþ), 461
(MþHþ)ꢀH2O; IR (neat) 3465, 2928, 1449, 1391, 1303, 1153 cmꢀ1
.
Anal. Calcd for C19H27O4SI: C, 47.70; H, 5.69. Found: C, 48.07; H, 5.62.

J. Chen et al. / Tetrahedron 64 (2008) 8899–8906
8905
4.2.9. (1R
*
,2R
*
,4S
*
,5S
*
)-1-Phenylsulfonyl-2-methyl-4-octyl-5-iodo-
,2R ,4S ,5S )-2i)
10.2 Hz, 1H), 4.19 (s, 1H), 3.79–3.76 (m, 2H), 2.45 (s, 3H), 2.23–2.10
3-oxabicyclo[3.1.0]hexan-2-ol ((1R
*
*
*
*
(m, 2H), 2.12 (d, J¼6.3 Hz, 1H), 1.59–1.49 (m, 1H), 1.57 (d, J¼6.6 Hz,
The reaction of 1i (52 mg, 0.15 mmol) and NIS (41þ17 mg,
1H), 1.00 (s, 3H); 13C NMR (75.4 MHz, CDCl3)
d 145.5, 135.7, 129.9,
0.26 mmol) in 2 mL of CH3CN and 0.2 mL of H2O afforded
129.6, 103.1, 81.2, 60.1, 54.9, 31.5, 23.5, 22.5, 21.7, 7.5; MS (ESI) m/z
456 (MþNHþ4 ), 421 (MþHþ)ꢀH2O; IR (neat) 3477, 2923, 1597, 1303,
1147 cmꢀ1; HRMS (MALDI) calcd for C15H19O5SINaþ (MþNa)þ:
460.9890. Found: 460.9898.
(1R
*
,2R
*
,4S
*
,5S
)-2i (55 mg, 72%) as a liquid. 1H NMR (300 MHz,
*
CDCl3)
d
8.06 (d, J¼7.5 Hz, 2H), 7.68 (t, J¼7.2 Hz, 1H), 7.56 (t,
J¼8.4 Hz, 2H), 4.22 (d, J¼6.3 Hz, 1H), 3.76 (s, 1H), 2.10 (d, J¼6.3 Hz,
1H), 1.91–1.84 (m, 1H), 1.57 (d, J¼6.3 Hz, 1H), 1.44–1.25 (m, 13H),
1.01 (s, 3H), 0.86 (t, J¼6.3 Hz, 3H); 13C NMR (75.4 MHz, CDCl3)
4.2.14. (1S
pentamethylene-5-iodo-3-oxabicyclo[3.1.0]hexan-2-ol
((1S ,2R ,5R )-2n)
*
,2R
*
,5R ) -1-(Ethoxycarbonyl)-2-methyl-4,4-
*
d
138.8, 134.2, 129.8, 128.9, 102.6, 82.4, 55.1, 31.8, 29.5, 29.3, 29.2,
29.1, 26.0, 23.5, 22.59, 22.56, 14.1, 8.3; MS (ESI) m/z 515 (MþNaþ),
475 (MþHþ)ꢀH2O; IR (neat) 3457, 2922, 1448, 1390, 1305,
1156 cmꢀ1; HRMS (MALDI) calcd for C20H29O4SINaþ: 515.0724.
Found: 515.0745.
*
*
*
The reaction of 1n (103 mg, 0.44 mmol) and NIS (118 mg,
0.52 mmol) in 2 mL of CH3CN and 0.2 mL of H2O afforded
(1S
*
,2R
*
,5R
)-2n (121 mg, 73%) as a solid, mp 56–57 ꢁC (petroleum
*
ether). 1H NMR (300 MHz, CDCl3)
d
5.08 (s, 1H), 4.39–4.18 (m, 2H),
4.2.10. (1R
*
,2R
*
,4S
*
,5S
*
)-1-p-Methylphenylsulfonyl-2-methyl-4-
2.20–2.16 (m, 1H), 1.89–1.79 (m, 1H), 1.72–1.39 (m, 12H), 1.34 (t,
octyl-5-iodo-3-oxabicyclo[3.1.0]hexan-2-ol ((1R
The reaction of 1j (39 mg, 0.12 mmol) and NIS (39 mg,
0.18 mmol) in 2 mL of CH3CN and 0.2 mL of H2O afforded
*
,2R ,4S ,5S )-2j)
*
*
*
J¼7.2 Hz, 3H), 1.24–1.12 (m, 1H); 13C NMR (75.4 MHz, CDCl3)
d 170.1,
102.8, 85.7, 61.9, 42.0, 37.8, 31.8, 25.6, 25.4, 24.9, 22.40, 22.36, 20.5,
14.2; MS (ESI) m/z 403 (MþNaþ), 363 (MþHþ)ꢀH2O; IR (neat) 3454,
2936, 1697, 1447, 1376, 1203 cmꢀ1; HRMS (MALDI) calcd for
(1R
*
,2R
*
,4S
*
,5S
)-2j (34 mg, 62%) as a liquid. 1H NMR (300 MHz,
*
CDCl3)
d
7.93 (d, J¼8.1 Hz, 2H), 7.36 (t, J¼8.1 Hz, 2H), 4.25–4.22 (m,
C
C
14H21O4INaþ (MþNaþ): 403.0377. Found: 403.0375. Anal. Calcd for
1H), 3.78 (s, 1H), 2.46 (s, 3H), 2.10 (d, J¼6.3 Hz, 1H), 1.91–1.85 (m,
1H), 1.56 (d, J¼6.6 Hz, 1H), 1.44–1.26 (m, 11H), 1.01 (s, 3H), 0.86 (t,
14H21O4I: C, 44.22; H, 5.71. Found: C, 44.17; H, 5.71.
J¼6.6 Hz, 3H); 13C NMR (75.4 MHz, CDCl3)
d
145.3, 135.9, 129.8,
4.2.15. (1R
pentamethylene-5-iodo-3-oxabicyclo[3.1.0]hexan-2-ol
((1R ,2R ,5S )-2o)
*
,2R
*
,5R
*
)-1-Phenylsulfonyl -2-methyl-4,4-
129.6, 102.6, 82.4, 55.0, 31.7, 29.5, 29.09, 29.06, 25.98, 23.5, 22.60,
22.58, 21.7, 14.1, 8.4; MS (ESI) m/z 515 (MþNaþ), 475 (MþHþ)ꢀH2O;
IR (neat) 3454, 2928, 1596, 1466, 1402, 1302, 1175 cmꢀ1; HRMS
(MALDI) calcd for C20H29O4SINaþ: 515.0724. Found: 515.0727.
*
*
*
The reaction of 1o (31 mg, 0.1 mmol) and NIS (27 mg,
0.12 mmol) in 2 mL of CH3CN and 0.2 mL of H2O afforded
(1R
*
,2R
*
,5S
)-2o (28 mg, 61%) as a solid, mp 102–104 ꢁC (de-
*
4.2.11. (1R
*
,2R
*
,4S
*
,5S
*
)-1-Phenylsulfonyl-2-methyl-4-cyclohexyl-
,2R ,4S ,5S )-2k)
composition). 1H NMR (300 MHz, CDCl3)
d
8.12 (d, J¼7.2 Hz, 2H),
5-iodo-3-oxabicyclo[3.1.0]hexan-2-ol ((1R
The reaction of 1k (38 mg, 0.12 mmol) and NIS (42 mg,
0.18 mmol) in 2 mL of CH3CN and 0.2 mL of H2O afforded
*
*
*
*
7.66 (t, J¼7.5 Hz, 1H), 7.54 (t, J¼7.5 Hz, 2H), 3.26 (s, 1H), 2.10 (d,
J¼6.3 Hz, 1H), 1.96–1.86 (m, 1H), 1.75–1.35 (m, 9H), 1.14 (s, 4H); 13
C
NMR (75.4 MHz, CDCl3) d 139.0, 133.9, 130.0, 128.6, 102.7, 84.4, 55.9,
(1R
*
,2R
*
,4S
*
,5S
*
)-2k (36 mg, 65%) as a solid, mp 118–119 ꢁC (pe-
38.0, 31.1, 26.1, 25.1, 24.5, 22.2, 22.1, 16.2; MS (EI) m/z 448 (Mþ,
troleum ether/ethyl acetate). 1H NMR (300 MHz, CDCl3)
d
8.07 (d,
21.61), 321 (100); IR (neat) 3479, 2936, 1577, 1447, 1307, 1150 cmꢀ1
;
J¼8.4 Hz, 2H), 7.68 (t, J¼7.2 Hz, 1H), 7.56 (t, J¼7.8 Hz, 2H), 4.10 (d,
J¼3.3 Hz, 1H), 3.84 (s, 1H), 2.21 (d, J¼6.3 Hz, 1H), 1.95–1.86 (m, 1H),
1.75–1.62 (m, 5H), 1.32–1.10 (m, 6H), 1.01 (s, 3H); 13C NMR
HRMS (ESI) calcd for C17H21O4ISNaþ (MþNaþ): 471.0097. Found:
471.0095.
(75.4 MHz, DMSO) d 139.6, 133.7, 129.9, 128.4, 102.0, 83.4, 54.4, 37.4,
Acknowledgements
30.2, 26.1, 26.0, 25.7, 25.6, 22.7, 22.6, 7.01; MS (ESI) m/z 485
(MþNaþ), 445 (MþHþ)ꢀH2O; IR (neat) 3427, 2852,1450,1387,1312,
1153 cmꢀ1. Anal. Calcd for C18H23O4SI: C, 46.76; H, 5.01. Found: C,
46.94; H, 5.11.
Financial support from the Major State Basic Research De-
velopment Program (2006CB806105) and National Natural Science
Foundation of China (20732005) is greatly appreciated.
4.2.12. (1R
hydroxyethyl)-5-iodo-3-oxabicyclo[3.1.0]hexan-2-ol
((1R ,2R ,4S ,5S )-2l)
*
,2R
*
,4S
*
,5S )-1-Phenylsulfonyl-2-methyl-4-(2-
*
Supplementary data
The 1H/13C NMR spectra of all the products. Supplementary data
associated with this article can be found in the online version, at
doi:10.1016/j.tet.2008.06.060.
*
*
*
*
The reaction of 1l (62 mg, 0.16 mmol) and NIS (55 mg,
0.24 mmol) in 2 mL of CH3CN and 0.2 mL of H2O afforded
(1R
*
,2R
*
,4S
*
,5S
)-2l (55 mg, 83%) as a liquid. 1H NMR (300 MHz,
*
CDCl3)
d
8.06 (d, J¼8.4 Hz, 2H), 7.68 (t, J¼7.5 Hz 1H), 7.56 (t,
References and notes
J¼8.1 Hz, 2H), 4.52 (s, 1H), 4.42 (dd, J¼10.2, 2.1 Hz, 1H), 3.76–3.71
(m, 2H), 2.22–2.11 (m, 2H), 2.12 (d, J¼6.9 Hz, 1H), 1.56 (d, J¼6.6 Hz,
1H), 1.57–1.47 (m, 1H), 1.02 (s, 3H); 13C NMR (75.4 MHz, CDCl3)
1. (a) Koft, E. R.; Smith, A. B., III. J. Am. Chem. Soc. 1982, 104, 2659; (b) Smith, A. B.,
III; Huryn, D. M. J. Org. Chem. 1985, 50, 1342; (c) Smith, A. B., III; Yokoyama, Y.;
Dunlap, N. K. Tetrahedron Lett. 1987, 28, 3663.
2. Mann, J.; Thomas, A. Tetrahedron Lett. 1986, 27, 3533.
3. Kohmoto, S. K.; Koyano, I.; Funabashi, T.; Kishikawa, K.; Yamamoto, M.; Yamada,
K. Tetrahedron Lett. 1995, 36, 553.
4. Epe, B.; Trautmann, D.; Mondon, A. Tetrahedron Lett. 1979, 20, 1365.
5. Martin, S. F.; Hom, R. K. Tetrahedron Lett. 1999, 40, 2887.
6. Tanaka, K.; Matsuura, H.; Funaki, I.; Suzuki, H. J. Chem. Soc., Chem. Commun.
1991, 1145.
7. Baird, M. S.; Huber, F. A.; Tverezovsky, V. V.; Bolesov, I. G. Tetrahedron 2000, 56,
4799.
8. For reviews, see: (a) Binger, P.; Bu¨ ch, H. M. Top. Curr. Chem. 1987, 135, 77; (b)
Ohta, T.; Takaya, H. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
Paquette, L. A., Eds.; Pergamon: Oxford, 1991; Vol. 5, p 1185; (c) Carbocyclic
Three-Membered Ring Compounds: Methods of Organic Chemistry (Houben-Weyl),
4th ed.; de Meijere, A., Ed.; 1997; Vol. E17, p 2217; (d) Lautens, M.; Klute, W.;
Tam, W. Chem. Rev. 1996, 96, 49; (e) Brandi, A.; Goti, A. Chem. Rev. 1998, 98, 589;
d
138.7, 134.2, 129.9, 128.9, 103.1, 80.8, 59.8, 55.0, 31.5, 23.4, 22.5,
7.6; MS (ESI) m/z 442 (MþNH4þ), 407 (MþHþ)ꢀH2O; IR (neat) 3474,
2926, 1447, 1307, 1150 cmꢀ1
C
;
HRMS (MALDI) calcd for
14H17O5SINaþ (MþNa) þ: 446.9734. Found: 446.9725.
4.2.13. (1R
hydroxyethyl)-5-iodo-3-oxabicyclo[3.1.0]hexan-2-ol
((1R ,2R ,4S ,5S )-2m)
*
,2R
*
,4S
*
,5S )-1-p-Methylphenylsulfonyl-2-methyl-4-(2-
*
*
*
*
*
The reaction of 1m (41 mg, 0.10 mmol) and NIS (35 mg,
0.15 mmol) in 2 mL of CH3CN and 0.2 mL of H2O afforded
(1R
*
,2R
*
,4S
*
,5S
*
)-2m (30 mg, 68%) as a liquid. 1H NMR (300 MHz,
CDCl3)
d
7.93 (d, J¼8.1 Hz, 2H), 7.36 (d, J¼8.1 Hz, 2H), 4.42 (dd, J¼1.8,

8906
J. Chen et al. / Tetrahedron 64 (2008) 8899–8906
(f) Nakamura, I.; Yammamoto, Y. Adv. Synth. Catal. 2002, 344, 111; (g) Brandi, A.;
unique: 17,364/6890 (R(int)¼0.0803), parameters 367. Supplementary crystal-
lographic data have been deposited at the Cambridge Crystallographic Data
Center. CCDC: 675219.
Cicchi, S.; Cordero, F. M.; Goti, A. Chem. Rev. 2003, 103, 1213.
9. (a) Noyori, R.; Hayashi, N.; Katoˆ, M. J. Am. Chem. Soc. 1971, 93, 4948; (b) Yamago,
S.; Nakamura, E. J. Am. Chem. Soc. 1989, 111, 7285; (c) Lautens, M.; Han, W. J. Am.
Chem. Soc. 2002, 124, 6312; (d) No¨tzel, M. W.; Rauch, K.; Labahn, T.; Meijere, A.
Org. Lett. 2002, 4, 839; (e) Lautens, M.; Han, W.; Liu, J. H.-.C. J. Am. Chem. Soc.
2003, 125, 4028; (f) Lu, L.; Chen, G.; Ma, S. Org. Lett. 2006, 8, 835; (g) Taillier, C.;
Lautens, M. Org. Lett. 2007, 9, 591; (h) Huang, X.; Yang, Y. Org. Lett. 2007, 9,
1667.
17. Crystal data for compound 2g: C16H21O4IS, MW¼436.29, monoclinic, space
group P2(1)/n, final R indices [I>2
s
(I)], R1¼0.0602, wR2¼0.1665, R indices (all
data), R1¼0.0925, wR2¼0.1838, a¼5.8129(7) Å, b¼23.903(3) Å, c¼13.1603(15) Å,
a
¼90ꢁ,
b
¼94.138(2)ꢁ,
g
¼90ꢁ, V¼1823.8(4) Å3, T¼293(2) K, Z¼4, reflections
collected/unique: 10,734/3964 (R(int)¼0.0746), parameters 192. Supplemen-
tary crystallographic data have been deposited at the Cambridge Crystallo-
graphic Data Center. CCDC: 609200.
10. Goti, A.; Anichini, B.; Brandi, A.; Kozhushkov, S.; Gratkowski, C.; Meijere, A.
J. Org. Chem. 1996, 61, 1665.
11. Bottini, A. T.; Cabral, L. J. Tetrahedron 1978, 34, 3187.
18. Crystal data for compound 2h: C19H27O4IS, MW¼478.37, monoclinic, space
group P2(1)/c, final R indices [I>2
s
(I)], R1¼0.0523, wR2¼0.1251, R indices (all
12. (a) Trost, B. M. Angew. Chem., Int. Ed. Engl. 1986, 25, 1; (b) Suginome, M.;
Matsuda, T.; Ito, Y. J. Am. Chem. Soc. 2000, 122, 11015; (c) Nakamura, I.; Oh, B. H.;
Saito, S.; Yamamoto, Y. Angew. Chem., Int. Ed. 2001, 40, 1298; (d) Camacho, D. H.;
Nakamura, I.; Saito, S.; Yamamoto, Y. J. Org. Chem. 2001, 66, 270; (e) Shi, M.; Xu,
B. Org. Lett. 2002, 4, 2145; (f) Huang, X.; Zhou, H. Org. Lett. 2002, 4, 4419; (g)
Delgado, A.; Rodriguez, J. R.; Castedo, L.; Mascaren˜as, J. L. J. Am. Chem. Soc. 2003,
125, 9282; (h) Krafft, M. E.; Bon˜aga, L. V. R.; Felts, A. S.; Hirosawa, C.; Kerrigan, S.
J. Org. Chem. 2003, 68, 6039.
data), R1¼0.0648, wR2¼0.1324, a¼18.310(2) Å, b¼8.3333(11) Å, c¼13.
8883(18) Å,
a
¼90ꢁ,
b
¼90.091(2)ꢁ,
g
¼90ꢁ, V¼2119.2(5) Å3, T¼293(2) K, Z¼4,
reflections collected/unique: 12,017/4625 (R(int)¼0.0958), parameters 230.
Supplementary crystallographic data have been deposited at the Cambridge
Crystallographic Data Center. CCDC: 675218.
19. Crystal data for compound 2c: C16H19O4I, MW¼402.21, triclinic, space group P-
1, final R indices [I>2
s
(I)], R1¼0.0306, wR2¼0.0878, R indices (all data), R1¼0.
0354, wR2¼0.1033, a¼9.2595(11) Å, b¼10.4975(12) Å, c¼10.5681(12) Å, ¼115.
a
13. (a) Ma, S.; Zhang, J. Angew. Chem., Int. Ed. 2003, 42, 183; (b) Ma, S.; Lu, L.; Zhang,
J. J. Am. Chem. Soc. 2004, 126, 9645.
14. Ma, S.; Lu, L. J. Org. Chem. 2005, 70, 7629.
660(5)ꢁ,
b
¼112.581(6)ꢁ,
g
¼92.261(6)ꢁ, V¼828.41(17) Å3, T¼296(2) K, Z¼2, re-
flections collected/unique: 6008/2806 (R(int)¼0.0198), parameters 190. Sup-
plementary crystallographic data have been deposited at the Cambridge
Crystallographic Data Center. CCDC: 690548.
15. Crystal data for compound 2e:
C
15H25O3I, MW¼380.25, monoclinic, space
group P2(1)/n, final R indices [I>2
s
(I)], R1¼0.0480, wR2¼0.0945, R indices
20. Crystal data for compound 2n: C14H21O4I, MW¼380.21, triclinic, space group P-
(all data), R1¼0.0699, wR2¼0.1032, a¼5.5873(7) Å, b¼23.713(3) Å, c¼
1, final R indices [I>2
s
(I)], R1¼0.0693, wR2¼0.1869, R indices (all data), R1¼0.
12.9064(17) Å,
a
¼90ꢁ,
b
¼100.286(6)ꢁ,
g
¼90ꢁ, V¼1682.5(4) Å3, T¼293(2) K,
0857, wR2¼2046, a¼13.4652(11) Å, b¼15.2074(12) Å, c¼16.2382(13) Å,
a
¼74.
Z¼4, reflections collected/unique: 9918/3646 (R(int)¼0.0854), parameters 176.
Supplementary crystallographic data have been deposited at the Cambridge
Crystallographic Data Center. CCDC: 675216.
6950(10)ꢁ,
b
¼71.977(2)ꢁ,
g
¼81.322(2)ꢁ, V¼3041.1(4) Å3, T¼293(2) K, Z¼8, re-
flections collected/unique: 16,151/11,183 (R(int)¼0.1319), parameters 703.
Supplementary crystallographic data have been deposited at the Cambridge
Crystallographic Data Center. CCDC: 675217.
16. Crystal data for compound 2f: C15H17O4I, MW¼388.19, orthorhombic, space
group Pca2(1), final R indices [I>2
s
(I)], R1¼0.0430, wR2¼0.1009, R indices (all
21. Taherirastgar, F.; Brandsma, L. Synth. Commun. 1997, 27, 4035.
22. Regitz, M.; Hocher, J. Org. Synth. Coll. 1973, V, 179.
23. Cheng, C.; Shimo, T.; Somekawa, K.; Baba, M. Tetrahedron 1998, 54, 2031.
data), R1¼0.0594, wR2¼0.1114, a¼24.413(4) Å, b¼5.5093(9) Å, c¼23.070(4) Å,
a
¼90ꢁ,
b
¼90ꢁ,
g
¼90ꢁ, V¼3148.5(9) Å3, T¼293(2) K, Z¼8, reflections collected/