Studies on the structure-enantioselectivity relationships in the catalytic asymmetric intramolecular cyclopropanation reaction of α-diazo-β-keto sulfones possessing a methyl-substituted phenyl group

Article abstract of DOI:10.1016/j.tetasy.2006.10.046

This manuscript describes studies on structure-enantioselectivity relationships in the catalytic asymmetric intramolecular cyclopropanation (IMCP) reaction of α-diazo-β-keto sulfones possessing a methyl-substituted phenyl group. Enantioselectivity of the

Full text of DOI:10.1016/j.tetasy.2006.10.046

Tetrahedron: Asymmetry 17 (2006) 2896–2906
Studies on the structure–enantioselectivity relationships in the
catalytic asymmetric intramolecular cyclopropanation reaction of
a-diazo-b-keto sulfones possessing a methyl-substituted phenyl group
Hiroyuki Takeda and Masahisa Nakada*
Department of Chemistry, Faculty of Science and Engineering, Waseda University, 3-4-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555, Japan
Received 15 September 2006; accepted 31 October 2006
Abstract—This manuscript describes studies on structure–enantioselectivity relationships in the catalytic asymmetric intramolecular
cyclopropanation (IMCP) reaction of a-diazo-b-keto sulfones possessing a methyl-substituted phenyl group. Enantioselectivity of the
IMCP reaction of the a-diazo-b-keto sulfones was varied by the position of a methyl group on the phenyl group in the substrate,
and the 2,3-dimethylphenyl sulfone 11h provided the product 12h in 95% yield with 93% ee. This yield is superior to that of the substrate
with a mesityl sulfone 11b, and the product 12h is useful because alkylation of its cyclopropane-opened b-keto sulfone derivative 15h
provides the C-alkylated product as a major product.
ꢀ 2006 Elsevier Ltd. All rights reserved.
R1 R1
1a: R1=Me, R2=Bn
1. Introduction
O
1b: R1=Me, R2=
1c: R1=Me, R2=
1d: R1=Et, R2=
1e: R1=Bn, R2=
i
-Pr
O
We have reported asymmetric catalysis of the intramolecu-
lar cyclopropanation (IMCP) reaction of various a-diazo-
b-keto sulfones 2, 3, 6, 7, and have succeeded in preparing
2-oxobicyclo[3.1.0]hexanes 4,1 2-oxobicyclo[4.1.0]heptanes
5,3 tricyclo[4.3.0.0]nonenes 8,1 and tricyclo[4.4.0.0]decenes
91,3 in high yield with excellent enantioselectivity (Scheme
1). This asymmetric reaction possesses wide applicabil-
ity4–7 and generates a highly crystalline product, providing
enantiopure chiral building blocks for the asymmetric total
synthesis of natural products. The asymmetric total synthe-
ses of (ꢀ)-malyngolide,5 (+)-allocyathin B2,6 and (ꢀ)-
methyl jasmonate7 in an enantiomerically pure form have
been reported utilizing this catalytic asymmetric IMCP
reaction from our laboratory; however, during our studies
on the asymmetric total synthesis of enantiopure (ꢀ)-
methyl jasmonate,7 we encountered a problem in that the
attempted C-alkylation of b-keto sulfone 10, which was
t-Bu
N
N
i
-Pr
-Pr
R2
R2
N2
i
R5
R3
R4
SO2Mes
R5
CuOTf (10 mol %)
R3
n
ligand 1e (15 mol %)
SO2Mes
n
R4
O
O
93-98% ee
Mes=2,4,6-trimethyl
4 (n=1): 5 (n=2)
2 (n=1): 3 (n=2)
CuOTf (10 mol %)
n
O
n
H
H
O
ligand 1b or 1e (15 mol %)
N2
MesO2S
MesO2S
n=1, 1e: 96% ee
n=2, 1b: 97% ee
6 (n=1): 7 (n=2)
8 (n=1): 9 (n=2)
Scheme 1. Asymmetric catalysis of a-diazo-b-keto sulfones 2, 3, 6, and 7.
derived from the corresponding cyclopropane
4
(R3@R4@R5@H), afforded an O-alkylated product as a
selectivity both in the IMCP reaction (83% ee, Table 1,
entry 3) and in the C-alkylation of the corresponding b-keto
sulfone derivative 13 (Scheme 3), and succeeded in utilizing
it for the asymmetric total synthesis of enantiopure (ꢀ)-
methyl jasmonate.7
major product (Scheme 2).
To overcome this problem, we devised the new substrate
11c possessing a less bulky 1-naphthyl group to attain good
*
The substrates 11a–d that have been prepared to date and
Corresponding author. Tel./fax: +813 5286 3240; e-mail: mnakada@
waseda.jp
the results of their IMCP reactions are summarized in
0957-4166/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.10.046

H. Takeda, M. Nakada / Tetrahedron: Asymmetry 17 (2006) 2896–2906
2897
MeI or
propargyl
bromide
propargyl
bromide
(3.0 equiv)
CN
R6
SO2Mes
CN
CN
CN
CN
CN
SO2Np
(3.0 equiv)
+
+
SO2Mes
SO2Mes
SO2Np
SO2Np
NaI
(3.0 equiv)
K2CO3
(1.5 equiv)
DMF, rt, 2 h
NaI
(3.0 equiv)
K2CO3
(1.5 equiv)
DMF, rt
O
O
O
R6
O
O
O
38% (R6=Me)
27% (R6=CH2CCH)
60% (R6=Me)
10
Np=1-naphthyl
63% (R6=CH2CCH)
75%
21%
13
Scheme 3. Alkylation of 13.
Scheme 2. Alkylation of 10.
Table 1. Results of the substrates with a 1-naphthyl group
11c or a 2,4-dimethylphenyl group 11d are rather unsatis-
factory because the enantioselectivity situates between
those of the phenyl sulfone 11a (73% ee, entry 1) and the
mesityl sulfone 11b (93% ee, entry 2). In addition, although
many successful examples for the catalytic asymmetric
IMCP of a-diazo ketones,2,8 a-diazo acetates,2 and a-diazo
acetamidates2,8 have been reported, the catalytic
asymmetric IMCP reaction of the a-diazo-b-keto com-
pound providing a bicyclo[3.1.0]hexane system with high
enantioselectivity is limited,1,4,6,7,9 thereby drawing our
attention to further studies.
of the a-diazo-b-keto sulfones possessing a methyl-substi-
tuted phenyl group and disclose the new substrate which
afforded a result superior to those previously reported.
2. Results and discussion
We prepared all the new a-diazo-b-keto sulfones 11e–l
(Table 2) possessing a methyl-substituted phenyl group
according to our reported method1,7 as shown in Scheme
4. Thus, the dianion of aryl methyl sulfone 14e–l10 was
reacted with ethyl 4-pentenoate to produce the correspond-
ing b-keto sulfone,11 which was converted to the a-diazo-b-
keto sulfone 11e–l in 72–88% yield. Use of the mono-anion
We report herein studies on structure–enantioselectivity
relationships in the catalytic asymmetric IMCP reaction
Table 1. Asymmetric catalysis of a-diazo-b-keto sulfones 11a–d
H
CuOTf (10 mol %)
ligand (15 mol %)
N2
SO2Ar
11a-d
SO2Ar
O
O
12a-d
Entry
1b
Ar
Ligand
Yield (%)
61
eea (%)
73
Temperature (ꢁC)
Time (h)
2
1e
rt
a
b
2b
1e
1d
87
93
93
83
rt, 50
2, 2.5c
3d
50
5
c
4d
1e
1e
82
97
79
81
50
50
2
5
5d
d
a All the products have (1R)-configuration. ee was determined by HPLC analysis. See Experimental for the conditions.
b Ref. 1.
c Reaction was carried out at the indicated temperatures for the indicated times, respectively.
d Ref. 7.

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H. Takeda, M. Nakada / Tetrahedron: Asymmetry 17 (2006) 2896–2906
Table 2. Asymmetric catalysis of a-diazo-b-keto sulfones 11e–l
H
CuOTf (10 mol %)
ligand (15 mol %)
N2
SO2Ar
11e-l
SO2Ar
12e-l
O
O
Entry
1
Ar
Ligand
Yield (%)
eea (%)
86
Temperature (ꢁC)
Time (h)
3
1e
1e
98
97
50
e
f
2
3
4
5
77
69
93
91
50
50
50
50
3
3
2
3
1e
1d
1e
95
95
82
g
h
6
7
1e
1d
1e
1e
1e
1e
90
83
82
72
94
91
82
90
91
83
72
62
50
50
50
70
50
50
5
3
i
j
8
96
48
5
9
10
11
k
l
5
a All the products have (1R)-configuration. ee was determined by HPLC analysis. See Experimental for the conditions.
of 14e–l resulted in low yield, probably because deprotona-
tion of the rather acidic methylene proton in the product by
the mono-anion occurred.11
at 50 ꢁC or 70 ꢁC (Table 2, entry 9); thus, the conditions
were the same as those used for the IMCP reaction of 2
(Scheme 1). Since ligand 1e provided the best ee in the
IMCP reactions of 11a, 11b, and 11d, ligand 1e was used
for all the reactions in Table 2. Nevertheless, the IMCP
reaction with ligand 1d sometimes gives a better result than
As all the IMCP reactions of various a-diazo-b-keto sulf-
ones 11e–l were sluggish, the reactions were carried out

H. Takeda, M. Nakada / Tetrahedron: Asymmetry 17 (2006) 2896–2906
2899
these results were unusual because the reaction of 11b pos-
sessing a more bulky mesityl sulfone with ligand 1e was
completed in 2.5 h at 50 ꢁC (Table 1, entry 2). Conse-
quently, now we are investigating this long-reaction time
induced by the 2,6-dimethylsulfonyl group in 11j and
ligand 1e.
1) n-BuLi (2.0 equiv)
THF, 0 oC
N2
CH3SO2Ar
SO2Ar
then,
O
14e-l
ethyl 4-pentenoate
2) TsN3, TEA
CH3CN, rt
11e-l
72-88% (2 steps)
The IMCP reaction of other substrates, the 3,4-dimethyl-
sulfone 11k (entry 10) and the 3,5-dimethylsulfone 11l
(entry 11) gave less productive results, affording products
with 72% ee and 62% ee, respectively.
Scheme 4. Preparation of 11e–l.
that with ligand 1e, as shown in entry 3 of Table 1; hence,
the IMCP reaction with ligand 1d was further carried out
for the substrate which afforded the product with over
90% ee (Table 2, entries 4 and 7).
In summary of the results in Table 2, all the substrates with
the 2-methyl substituted phenyl sulfone 11e, 11h–j (entries
1, 4–9) afforded products with over 82% ee, and other sub-
strates lacking a methyl substituent at their 2-position. 11f,
11g, 11k, 11l (entries 2, 3, 10, 11, respectively) gave prod-
ucts with less than 77% ee. This trend of the structure–
enantioselectivity relationship is consistent with that in
Table 1, indicating that the 2-methyl group of the phenyl
sulfonyl group is important to attain the high
enantioselectivity in the IMCP reaction of 11.
First, we carried out the IMCP reactions of 11e–g possess-
ing a methylphenyl sulfone (entries 1–3). The reactions of
11e–g smoothly produced the corresponding 12e–g in
excellent yield with the ee ranging from 69% ee to 86% ee.
The IMCP reaction of the 2-methylphenyl sulfone 11e
(entry 1) was the most enantioselective among the mono-
substituted phenyl sulfones 11e–g (entries 1–3), affording
the product 12e with 86% ee. This ee was higher than that
of the phenyl sulfone 11a (73% ee, Table 1, entry 1) and the
2,4-dimethylphenyl sulfone 11d (81% ee, Table 1, entry 5),
but lower than that of the mesityl sulfone 11b (93% ee,
Table 1, entry 2).
All the products 12e–l in Table 2 were converted to 16
(Scheme 5) to determine their absolute configuration by
comparing their sign of the specific rotations with that of
the known compound 16.7 Thus, reactions of 12e–l with
sodium cyanide in DMSO at 80 ꢁC smoothly produced the
b-keto sulfones 15e–l, respectively, and their subsequent
desulfonylations with SmI2 successfully afforded 16. The
specific rotations of all the products 16 had a minus sign,
indicating that all the products 12e–l in Table 2 possess
(1R) configuration. This sense of enantioselectivity is well
explained by the previously proposed model A (Fig. 1).1
Enantioselectivity of the IMCP reaction of the 3-methyl-
phenyl sulfone 11f (entry 2) was slightly higher than that
of the phenyl sulfone 11a, but lower than the 2-methyl-
phenyl sulfone 11e (entry 1).
In the case of the 4-methylphenyl sulfone 11g (entry 3), the
enantioselectivity was lowest among the entries 1–3 and
lower than that of the phenyl sulfone 11a. The ee of the
products in entries 1–3 was in the order: 2-methylphenyl
sulfone 12e > 3-methylphenyl sulfone 12f > 4-methyl-
phenyl sulfone 12g.
From this model, the 2-methyl group of the phenyl sulfonyl
group is surmised to be important for the high enantio-
selectivity because the increased steric hindrance around
the carbene center would prevent its reaction from the
si-face. Nevertheless, a careful analysis and discussion is
required to account for the observed structure–enantioselec-
tivity relationship because various factors could influence
the enantioselectivity, and the rationale as well as the quan-
Next, we carried out the IMCP reaction of dimethylphenyl
sulfones 11h–l (entries 4–11). The IMCP reaction of the
2,3-dimethylphenyl sulfone 11h (entry 5) afforded the prod-
uct 12h with 91% ee, and the reaction of 11h with ligand 1d
(entry 4) gave the product 12h with the highest ee (93% ee),
and this ee was the same as that of the mesityl sulfone 11b
(Table 1, entry 2); furthermore, the yield in entry 4 was bet-
ter than that in entry 2 of Table 1. That is, the 2,3-dimeth-
ylphenyl sulfone 11h was the best substrate which gave the
2-oxobicyclo[3.1.0]hexane system.
CN
NaCN
SO2Ar
SO2Ar
15e-l
DMSO
80 oC
5 h
O
O
12e-l
-78 oC
5 min
Enantioselectivity of the IMCP reaction of the 2,5-dimeth-
ylphenyl sulfone 11i (82% ee, entry 6) was comparable with
that of 2,4-dimethylphenyl sulfone 11d (81% ee, Table 1,
entry 5). The reaction of the 2,6-dimethylsulfone 11j (entry
8) afforded a product with 91% ee; hence, the reaction with
ligand 1d was also carried out, but the enantioselectivity
was not increased (90% ee, entry 7). Interestingly, com-
pared with entry 7, the reaction of 11j (entry 8) was very
slow and required 96 h to be completed. This was reduced
to 48 h by the elevated temperature (entry 9). Nonetheless,
SmI2, THF
methanol
CN
CN
SmI2, THF
methanol
SO2Mes
-78 oC
5 min
O
O
16
10
Scheme 5. Conversion of 12e–l to 16.

2900
H. Takeda, M. Nakada / Tetrahedron: Asymmetry 17 (2006) 2896–2906
4. Experimental
4.1. General procedures
O
SO2
N
N
1H and 13C NMR spectra were recorded on a JEOL AL-
Cu
1
400 spectrometer. H and 13C chemical shifts are reported
O
in ppm downfield from tetramethylsilane (TMS, d scale)
with the solvent resonances as internal standards. The fol-
lowing abbreviations were used to explain the multiplici-
ties: s, singlet; d, doublet; t, triplet; q, quartet; m,
multiplet; band, several overlapping signals; b, broad. IR
spectra were recorded on a JASCO FT/IR-8300. Melting
points (mp) are uncorrected, recorded on a Yamato capil-
lary melting point apparatus equipped with a digital ther-
mometer. Optical rotations were measured using a 2 mL
cell with a 1 dm path length on a JASCO DIP-1000. Chiral
HPLC analysis was performed on a JASCO PU-980 and
UV-970. Mass spectrometric analyses and elemental analy-
ses were provided at the Materials Characterization Cen-
tral Laboratory, Waseda University. All reactions were
carried out under an argon atmosphere with dry, freshly
distilled solvents under anhydrous conditions, unless other-
wise noted. All reactions were monitored by thin-layer
chromatography carried out on 0.25 mm E. Merck silica
gel plates (60F-254) using UV light as visualizing agent
and phosphomolybdic acid and heat as developing agents.
E. Merck silica gel (60, particle size 0.040–0.063 mm) was
used for flash column chromatography. Preparative thin-
layer chromatography (PTLC) separations were carried
out on self-made 0.3 mm E. Merck silica gel plates (60F-
254). THF was distilled from sodium/benzophenone ketyl
and methylene chloride (CH2Cl2), benzene was distilled
from calcium hydride. Toluene was distilled from sodium.
Acetonitrile was distilled from CaH2 under reduced pres-
sure. (CuOTf)2C6H6 and all other reagents were purchased
from Aldrich, TCI, or Kanto Chemical Co. Ltd.
O
re-face attack
model A (for entry 2, Table 1)
Figure 1. Proposed model A.1
titative analysis await further studies on this IMCP reac-
tion and theoretical calculations.
To explore the utility of 11h as a chiral building block,
alkylation of 15h was examined (Scheme 6). b-Keto sulfone
15h, obtained by the reaction of 11h with sodium cyanide
in DMSO at 80 ꢁC (Scheme 5), was subjected to the alkyl-
ation reaction (Scheme 6). The reaction of 15h with methyl
iodide provided C-methylated product 17C (66%) and O-
methylated product 17O (27%), and the reaction with
propargyl bromide afforded C-propargylated product 18C
(58%) and O-propargylated product 18O (33%), indicating
that 11h is superior to the corresponding mesityl sulfone 10
(Scheme 2) in the C-alkylation selectivity.
3. Conclusion
In summary, structure–enantioselectivity relationships in
the catalytic asymmetric IMCP reaction of the a-diazo-b-
keto sulfones possessing a methyl-substituted phenyl group
have been studied. The enantioselectivity was varied by the
position of the methyl group on the phenyl sulfone, and the
2-methyl group of the phenyl sulfonyl group was important
to attain the high enantioselectivity in the IMCP reactions
of new substrates11a–l. The sense of enantioselectivity in
all the IMCP reactions of 11e–l was well explained by the
previously proposed model A. The new chiral building
block 12h was produced in 95% yield with 93% ee, and
the alkylation reaction of its cyclopropane-opened deriva-
tive 15h showed a good C-alkylation selectivity. These
results are superior to those obtained to date, thereby
making the new chiral building block 12h useful for the
asymmetric total synthesis of natural products. Studies
on the use of 12h are now ongoing in our laboratory and
will be reported in due course.
4.2. 1-(2-Methylphenylsulfonyl)-5-hexen-2-one
Procedure A: To a solution of methyl 2-methylphenyl
sulfone (300.0 mg, 1.76 mmol) in THF (8 mL) was added
n-BuLi (2.21 mL, 3.52 mmol) at 0 ꢁC, and the solution was
stirred for 1.5 h at room temperature. To this stirred solu-
tion was added ethyl 4-pentenoate (237.0 mg, 1.85 mmol)
in THF (1 mL · 2) via a cannula. The reaction mixture
was stirred at 0 ꢁC for 1 h and quenched with saturated
aqueous NH4Cl solution (5 mL), and extracted with Et2O
(3 mL · 2). The combined organic layer was washed with
brine (5 mL), dried over Na2SO4, and evaporated. The
MeI or
CN
CN
CN
propargyl
bromide
R6
(3.0 equiv)
+
SO2Ar
SO2Ar
SO2Ar
NaI
(3.0 equiv)
K2CO3
(1.5 equiv)
DMF, rt
O
O
O
R6
15h
17C (R6=Me)
17O (R6=Me)
66%
58%
27%
33%
18C (R6=CH2CCH)
18O (R6=CH2CCH)
Ar=2,3-dimethylphenyl
Scheme 6. Alkylation of 15h.

H. Takeda, M. Nakada / Tetrahedron: Asymmetry 17 (2006) 2896–2906
2901
residue was purified by flash chromatography (hexane/
ethyl acetate = 4/1) to afford 1-(2-methylphenylsulfonyl)-
5-hexen-2-one (408.0 mg, 92%) as a white solid: mp 30–
32 ꢁC (CH2Cl2/hexane); IR (KBr) mmax 1684, 884,
a white solid. The absolute configuration was determined
as described in the text. Ee was determined by HPLC
(254 nm); Daicel CHIRALPAK AS-H 0.46 cm B · 25 cm;
hexane/2-propanol = 4/1; flow rate = 0.5 mL/min; reten-
tion time: 48.0 min for the minor enantiomer, 50.0 min for
734 cmꢀ1
;
1H NMR (400 MHz, CDCl3): d 7.93 (d,
J = 8.1 Hz, 1H), 7.54 (dd, J = 7.6, 7.6 Hz, 1H), 7.37 (dd,
J = 7.6, 8.1 Hz, 1H), 7.35 (d, J = 7.6 Hz, 1H), 5.74 (ddt,
J = 6.6, 10.0, 17.0 Hz, 1H), 5.04 (dd, J = 1.7, 17.0 Hz,
1H), 4.98 (dd, J = 1.7, 10.0 Hz, 1H), 4.19 (s, 2H), 2.81 (t,
J = 7.1 Hz, 2H), 2.69 (s, 3H), 2.30 (dt, J = 6.6, 7.1 Hz,
2H); 13C NMR (100 MHz, CDCl3): d 197.1, 137.6, 136.6,
134.2, 134.1, 132.7, 130.1, 126.6, 115.6, 66.0, 43.4, 27.0,
20.2; HRMS(FAB): calcd for C13H16O3S+H 253.0898,
found 253.0904.
the major enantiomer: mp 90–92 ꢁC (hexane/CH2Cl2);
25
½aꢁD = ꢀ35.4 (c 1.00, CHCl3, 86% ee); IR (KBr) mmax
:
1
1736, 968, 816 cmꢀ1; H NMR (400 MHz, CDCl3): d 8.08
(d, J = 7.8 Hz, 1H), 7.50 (dd, J = 7.3, 7.3 Hz, 1H), 7.38
(dd, J = 7.3, 7.8 Hz, 1H), 7.30 (d, J = 7.3 Hz, 1H), 3.08–
3.00 (m, 1H), 2.70 (s, 3H), 2.40–2.20 (m, 4H), 2.15–2.00
(m, 1H), 1.63 (dd, J = 5.6, 5.6 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d 203.5, 138.3, 137.6, 133.6, 132.5,
131.4, 126.3, 53.4, 33.5, 30.7, 20.8, 20.3; HRMS(FAB):
calcd for C13H14O3S+H 251.0742, found 251.0752.
4.3. 1-Diazo-1-(2-methylphenylsulfonyl)-5-hexen-2-one 11e
4.5. 1-(3-Methylphenylsulfonyl)-5-hexen-2-one
Procedure B: To a solution of 1-(2-methylphenylsulfonyl)-
5-hexen-2-one (300.0 mg, 1.19 mmol) in CH3CN (5 mL)
was added triethylamine (0.40 mL, 2.85 mmol) at 0 ꢁC
and then a solution of p-toluenesulfonyl azide (280.0 mg,
1.42 mmol) in CH3CN (2.5 mL · 2) via a cannula. The
reaction mixture was stirred at room temperature for 8 h.
The solution was concentrated under vacuum and diluted
with ether (20 mL). This solution was washed with 0.1 M
KOH aqueous solution (5 mL), and the organic was sepa-
rated, washed with brine (5 mL), dried over Na2SO4, and
evaporated. The residue was purified by flash chromato-
graphy (hexane/EtOAc = 20/1) to afford 1-diazo-1-(2-meth-
ylphenylsulfonyl)-5-hexen-2-one 11e (288.0 mg, 87%) as a
greenish yellow solid: IR (KBr) mmax 1676, 917, 806,
This compound was prepared and purified by the previ-
ously described Procedure A, and was obtained as a color-
less oil (93%): IR (neat) mmax 1684, 858, 732 cmꢀ1 1H
;
NMR (400 MHz, CDCl3): d 7.78–7.64 (m, 2H), 7.63–7.35
(m, 2H), 5.70 (ddt, J = 6.6, 10.0, 17.0 Hz, 1H), 5.01–4.89
(m, 2H), 4.11 (s, 2H), 2.74 (t, J = 6.8 Hz, 2H), 2.38 (s,
3H), 2.24 (dt, J = 6.6, 6.8 Hz, 2H); 13C NMR (100 MHz,
CDCl3): d 197.3, 139.5, 138.3, 136.0, 135.0, 129.0, 128.3,
125.2, 115.6, 66.6, 43.2, 26.8, 21.2; HRMS(FAB): calcd
for C13H16O3S+H 253.0898, found 253.0901.
4.6. 1-Diazo-1-(3-methylphenylsulfonyl)-5-hexen-2-one 11f
763 cmꢀ1
;
1H NMR (400 MHz, CDCl3): d 8.12 (d,
J = 7.8 Hz, 1H), 7.55 (dd, J = 7.6, 7.6 Hz, 1H), 7.42 (dd,
J = 7.6, 7.8 Hz, 1H), 7.37 (d, J = 7.6 Hz, 1H), 5.61 (ddt,
J = 6.6, 10.0, 17.0 Hz, 1H), 4.92 (dd, J = 1.5, 17.0 Hz,
1H), 4.84 (dd, J = 1.5, 10.0 Hz, 1H), 2.61 (s, 3H), 2.54 (t,
J = 7.1 Hz, 2H), 2.35 (dt, J = 6.6, 7.1 Hz, 2H); 13C NMR
(100 MHz, CDCl3): d 187.9, 137.1, 135.8, 134.1, 133.0,
130.2, 126.6, 115.6, 38.0, 27.4, 20.0, 19.9: HRMS(FAB):
calcd for C13H14N2O3S+H 279.0803, found 279.0812.
This compound was prepared and purified by the previ-
ously described Procedure B, and was obtained as a green-
ish yellow oil (86%): IR (neat) mmax 1658, 916, 846 cmꢀ1
;
1H NMR (400 MHz, CDCl3): d 7.83–7.70 (m, 2H), 7.55–
7.43 (m, 2H), 5.72 (ddt, J = 6.3, 10.0, 16.0 Hz, 1H), 5.05–
4.88 (m, 2H), 2.66 (t, J = 7.0 Hz, 2H), 2.46 (s, 3H), 2.31
(dt, J = 6.3, 7.0 Hz, 2H); 13C NMR (100 MHz, CDCl3): d
187.7, 141.7, 139.8, 136.0, 134.9, 133.7, 129.2, 127.4,
115.7, 38.1, 27.4, 21.3: HRMS(FAB): calcd for
C13H14N2O3S+H 279.0803, found 279.0812.
4.4. (1R,5R)-1-(2-Methylphenylsulfonyl)bicyclo[3.1.0]hexan-
2-one 12e
Procedure C: A toluene azeotroped [CuOTf]2ÆC6H6 (9.3 mg,
0.0179 mmol, 10 mol % as CuOTf) was placed in a dried
flask (10 mL) under Ar atmosphere and to this flask was
added toluene (3 mL) and then a solution of toluene azeo-
troped ligand 1e (22.3 mg, 0.0537 mmol, 15 mol %) in toluene
(0.5 mL · 2) via a cannula. The mixture was stirred at room
temperature for 0.5 h and then to the light blue solution was
added a solution of toluene azeotroped 1-diazo-1-(2-methyl-
phenylsulfonyl)-5-hexen-2-one 11e (100.0 mg, 0.359 mmol)
in toluene (0.5 mL · 2) via a cannula. The reaction mixture
was stirred at 50 ꢁC for 3 h, quenched with a mixture of
saturated aqueous NH4Cl solution (1 mL) and NH4OH
aqueous solution (1.5 mL), and extracted with ether
(1 mL · 2). The combined organic layer was washed with
brine (1 mL), dried over Na2SO4, and evaporated. The res-
idue was purified by flash chromatography (hexane/
EtOAc = 3/1) to afford (1R,5R)-1-(2-methylphenylsulfon-
yl)bicyclo[3.1.0]hexan-2-one 12e (88.0 mg, 98%, 86% ee) as
4.7. (1R,5R)-1-(3-Methylphenylsulfonyl)bicyclo[3.1.0]hexan-
2-one 12f
This compound was prepared and purified by the previously
described Procedure A, and was obtained as a white solid
(97%, 77% ee). Ee was determined by HPLC (254 nm);
Daicel CHIRALCEL OD-H 0.46 cm B · 25 cm; hexane/
2-propanol = 20/1; flow rate = 0.5 mL/min; retention time:
53.0 min for the major enantiomer, 56.0 min for the minor
26
enantiomer; mp 90–92 ꢁC (hexane/CH2Cl2); ½aꢁD = ꢀ35.8
(c 1.50, CHCl3, 77% ee) ; IR (KBr) mmax 1718, 923,
1
826 cmꢀ1; H NMR (400 MHz, CDCl3): d 7.91–7.77 (m,
2H), 7.60–7.32 (m, 2H), 3.07–3.00 (m, 1H), 2.34 (s, 3H),
2.40–2.20 (m, 4H), 2.15–1.98 (m, 1H), 1.54 (dd, J = 5.6,
5.6 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 203.4, 139.2,
139.1, 134.5, 129.0, 128.9, 125.9, 53.1, 33.6, 31.1, 20.4,
20.2; HRMS(FAB): calcd for C13H14O3S+H 251.0742,
found 251.0744.

2902
H. Takeda, M. Nakada / Tetrahedron: Asymmetry 17 (2006) 2896–2906
4.8. 1-(4-Methylphenylsulfonyl)-5-hexen-2-one
4.12. 1-Diazo-1-(2,3-dimethylphenylsulfonyl)-5-hexen-2-one
11h
This compound was prepared and purified by the previ-
ously described Procedure A, and was obtained as a white
solid (90%): mp 31–33 ꢁC (hexane/CH2Cl2); IR (KBr) mmax
This compound was prepared and purified by the previ-
ously described Procedure B, and was obtained as a green-
1644, 813, 735 cmꢀ1; H NMR (400 MHz, CDCl3) d 7.75
ish-yellow solid (95%): IR (KBr) mmax 1678, 838, 739 cmꢀ1
;
1
(d, J = 8.0 Hz, 2H), 7.36 (d, J = 7.8 Hz, 2H), 5.76 (ddt,
J = 6.8, 10.0, 17.0 Hz, 1H), 5.08–4.95 (m, 2H), 4.15 (s,
2H), 2.80 (t, J = 7.3 Hz, 2H), 2.44 (s, 3H), 2.30 (dt,
J = 6.8, 7.3 Hz, 2H); 13C NMR (100 MHz, CDCl3) d
187.6, 145.3, 138.9, 135.9, 129.9, 127.2, 127.1, 115.7, 38.0,
27.4, 21.5; HRMS(FAB): calcd for C13H16O3S+H
253.0898, found 253.0904.
1H NMR (400 MHz, CDCl3): d 8.00 (d, J = 8.0 Hz, 1H),
7.45 (d, J = 7.5 Hz, 1H), 7.30 (dd, J = 7.5, 8.0 Hz, 1H),
5.62 (ddt, J = 6.8, 9.0, 17.0 Hz, 1H), 4.89 (dd, J = 1.5,
17.0 Hz, 1H), 4.83 (dd, J = 1.5, 9.0 Hz, 1H), 2.53 (t,
J = 7.3 Hz, 2H), 2.50 (s, 3H), 2.36 (s, 3H), 2.22 (dt,
J = 6.8, 7.3 Hz, 2H); 13C NMR (100 MHz, CDCl3): d
187.9, 139.8, 139.6, 135.8, 128.0, 127.8, 125.8, 125.7,
115.4, 37.8, 27.2, 20.3, 15.7: HRMS(FAB): calcd for
C14H16N2O3S+H 293.0960, found 293.0966.
4.9. 1-Diazo-1-(4-methylphenylsulfonyl)-5-hexen-2-one 11g
4.13. (1R,5R)-1-(2,3-Dimethylphenylsulfonyl)bicyclo[3.1.0]-
hexan-2-one 12h
This compound was prepared and purified by the previ-
ously described Procedure B, and was obtained as a green-
ish-yellow oil (87%): IR (neat) mmax 1654, 820, 740 cmꢀ1
;
This compound was prepared and purified by the previ-
ously described Procedure C, and was obtained as a white
solid (95%, 93% ee, using ligand 1d). Ee was determined by
HPLC (254 nm); Daicel CHIRALPAK AS-H 0.46 cm
B · 25 cm; hexane/2-propanol = 4/1; flow rate = 0.5 mL/
min; retention time: 44.0 min for the minor enantiomer,
1H NMR (400 MHz, CDCl3): d 7.85 (d, J = 8.2 Hz, 2H),
7.37 (d, J = 8.2 Hz, 2H), 5.72 (ddt, J = 6.8, 10.0, 17.0 Hz,
1H), 5.02–4.90 (m, 2H), 2.64 (t, J = 7.5 Hz, 2H), 2.45 (s,
3H), 2.30 (dt, J = 6.8, 7.5 Hz, 2H); 13C NMR (100 MHz,
CDCl3): d 187.6 145.3, 138.9, 135.9, 129.9, 127.2, 115.7,
38.0, 27.3, 21.5; HRMS(FAB): calcd for C13H14N2O3S+H
279.0803, found 279.0812.
49.0 min for the major enantiomer; mp 99–101 ꢁC (hex-
26
ane/CH2Cl2); ½aꢁD = ꢀ37.2 (c 1.02, CHCl3, >99% ee); IR
(KBr) mmax 1732, 927, 863 cmꢀ1 1H NMR (400 MHz,
;
CDCl3): d 7.97 (d, J = 8.0 Hz, 1H), 7.40 (d, J = 7.6 Hz,
1H), 7.27 (dd, J = 7.6, 8.0 Hz, 1H), 3.07–3.00 (m, 1H),
2.59 (s, 3H), 2.38–2.31 (m, 4H including d 2.34, s, 3H),
2.30–2.16 (m, 3H), 2.14–2.00 (m, 1H), 1.64 (dd, J = 5.4,
5.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 203.5,
139.1, 136.4, 135.1, 129.1, 129.0, 53.4, 33.4, 31.1, 20.7,
20.6, 20.2, 16.6; HRMS(FAB): calcd for C14H16O3S+H
265.0898, found 265.0898.
4.10. (1R,5R)-1-(4-Methylphenylsulfonyl)bicyclo[3.1.0]-
hexan-2-one 12g
This compound was prepared and purified by the previ-
ously described Procedure C, and was obtained as a white
solid (95%, 69% ee). Ee was determined by HPLC
(254 nm);
Daicel
CHIRALPAK
AS-H
0.46 cm
B · 25 cm; hexane/2-propanol = 4/1; flow rate = 0.5 mL/
min; retention time: 78.0 min for the major enantiomer,
4.14. 1-(2,5-Dimethylphenylsulfonyl)-5-hexen-2-one
82.0 min for the minor enantiomer; mp 96–98 ꢁC (hex-
28
ane/CH2Cl2); ½aꢁD = ꢀ25.2 (c 0.75, CHCl3, 69% ee); IR
(KBr) mmax 1731, 967, 810 cmꢀ1 1H NMR (400 MHz,
;
This compound was prepared and purified by the previ-
ously described Procedure A, and was obtained as a color-
CDCl3) d 7.92 (d, J = 8.0 Hz, 2H), 7.34 (d, J = 7.8 Hz,
2H), 3.07–3.00 (m, 1H), 2.44 (s, 3H), 2.30–2.15 (m, 4H),
2.10–1.95 (m, 1H), 1.51 (dd, J = 5.6, 5.6 Hz, 1H); 13C
NMR (100 MHz, CDCl3): d 203.8, 144.7, 136.4, 129.5,
128.8, 53.2, 33.6, 31.0, 21.8, 20.3; HRMS(FAB): calcd for
C13H14O3S+H 251.0742, found 251.0740.
less oil (94%): IR (neat) mmax 1642, 916, 831 cmꢀ1 1H
;
NMR (400 MHz, CDCl3): d 7.64 (s, 1H), 7.24 (d
J = 7.6 Hz, 1H), 7.14 (d, J = 7.6 Hz, 1H), 5.65 (ddt,
J = 6.8, 10.0, 17.0 Hz, 1H), 4.94 (dd, J = 1.5, 17.0 Hz,
1H), 4.89 (dd, J = 1.5, 10.0 Hz, 1H), 4.11 (s, 2H), 2.71 (t,
J = 7.1 Hz, 2H), 2.54 (s, 3H), 2.28 (s, 3H), 2.20 (dt,
J = 6.8, 7.1 Hz, 2H); 13C NMR (100 MHz, CDCl3): d
196.9, 136.3, 135.9, 134.7, 134.5, 132.5, 129.9, 129.8,
115.4, 65.8, 43.1, 26.7, 20.3, 19.4; HRMS(FAB): calcd for
C14H18O3S+H 267.1055, found 267.1057.
4.11. 1-(2,3-Dimethylphenylsulfonyl)-5-hexen-2-one
This compound was prepared and purified by the previ-
ously described Procedure A, and was obtained as a color-
less oil (93%): IR (neat) mmax 1690, 839, 730 cmꢀ1
;
1H
4.15. 1-Diazo-1-(2,5-dimethylphenylsulfonyl)-5-hexen-2-one
11i
NMR (400 MHz, CDCl3): d 7.83 (d, J = 8.0 Hz, 1H),
7.44 (d, J = 7.5 Hz, 1H), 7.36 (dd, J = 7.5, 8.0 Hz, 1H),
5.76 (ddt, J = 7.0, 10.0, 17.0 Hz, 1H), 5.02 (dd, J = 1.5,
17.0 Hz, 1H), 4.98 (dd, J = 1.5, 10.0 Hz, 1H), 4.20 (s,
2H), 2.81 (t, J = 7.3 Hz, 2H), 2.60 (s, 3H), 2.35 (s, 3H),
2.28 (dt, J = 7.0, 7.3 Hz, 2H); 13C NMR (100 MHz,
CDCl3): d 197.2, 139.7, 137.1, 136.2, 136.0, 135.7, 127.7,
125.9, 115.6, 66.3, 43.3, 26.9, 20.4, 16.1; HRMS(FAB):
calcd for C14H18O3S+H 267.1055, found 267.1062.
This compound was prepared and purified by the previ-
ously described Procedure B, and was obtained as a green-
ish yellow oil (85%): IR (neat) mmax 1670, 916, 730 cmꢀ1; 1H
NMR (400 MHz, CDCl3): d 7.81 (s, 1H), 7.23 (d,
J = 7.6 Hz, 1H), 7.13 (d, J = 7.6 Hz, 1H), 5.52 (ddt,
J = 6.6, 10.0, 17.0 Hz, 1H), 4.84 (dd, J = 1.5, 17.0 Hz,
1H), 4.75 (dd, J = 1.5, 10.0 Hz, 1H), 2.45 (t, J = 6.9 Hz,

H. Takeda, M. Nakada / Tetrahedron: Asymmetry 17 (2006) 2896–2906
2903
2H), 2.43 (s, 3H), 2.29 (s, 3H), 2.08 (dt, J = 6.6, 6.9 Hz,
2H); 13C NMR (100 MHz, CDCl3): d 187.8, 139.0, 136.0,
134.9, 134.1, 133.0, 130.3, 130.2, 115.4, 37.9, 27.4, 20.7,
19.5: HRMS(FAB): calcd for C14H16N2O3S+H 293.0960,
found 293.0956.
B · 25 cm; hexane/2-propanol = 4/1; flow rate = 0.5 mL/
min; retention time: 21.0 min for the major enantiomer,
23.0 min for the minor enantiomer; mp 98–100 ꢁC (hex-
28
ane/CH2Cl2); ½aꢁD = ꢀ50.0 (c 1.25, CHCl3, 91% ee); IR
(KBr) mmax 1731, 874, 790 cmꢀ1 1H NMR (400 MHz,
;
CDCl3): d 7.36–7.28 (m, 1H), 7.18–7.11 (m, 2H), 3.05–
2.96 (m, 1H) 2.73 (s, 6H), 2.48–2.38 (m, 1H), 2.32–2.18
(m, 3H), 2.12–2.02 (m, 1H), 1.66 (dd, J = 5.6, 5.6 Hz,
1H); 13C NMR (100 MHz, CDCl3): d 204.0, 140.9, 132.8,
131.4, 129.6, 55.1, 33.4, 31.6, 23.3, 20.7, 20.4;
HRMS(FAB): calcd for C14H16O3S+H 265.0898, found
265.0897.
4.16. (1R,5R)-1-(2,5-Dimethylphenylsulfonyl)bicyclo[3.1.0]-
hexan-2-one 12i
This compound was prepared and purified by the previ-
ously described Procedure C, and was obtained as a white
solid (90%, 82% ee). Ee was determined by HPLC
(254 nm);
Daicel
CHIRALPAK
AS-H
0.46 cm
B · 25 cm; hexane/2-propanol = 4/1; flow rate = 0.5 mL/
min; retention time: 36.0 min for the major enantiomer,
4.20. 1-(3,4-Dimethylphenylsulfonyl)-5-hexen-2-one
39.0 min for the minor enantiomer; mp 96–98 ꢁC (hex-
This compound was prepared and purified by the previ-
28
ane/CH2Cl2); ½aꢁD = ꢀ43.0 (c 1.05, CHCl3, 82% ee); IR
ously described Procedure A, and was obtained as a color-
(KBr) mmax 1740, 964, 882 cmꢀ1 1H NMR (400 MHz,
;
less oil (96%): IR (neat) mmax 1680, 929, 818 cmꢀ1 1H
;
CDCl3): d 7.88 (s, 1H), 7.29 (d, J = 7.8 Hz, 1H), 7.17 (d,
J = 7.8 Hz, 1H), 3.06–2.90 (m, 1H), 2.64 (s, 3H), 2.40 (s,
3H), 2.39–2.14 (m, 4H), 2.12–1.99 (m, 1H), 1.60 (dd,
J = 5.4, 5.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): d
203.4, 137.2, 136.1, 135.1, 134.3, 132.4, 131.6, 53.5, 33.5,
30.7, 20.8, 20.4, 20.3; HRMS(FAB): calcd for
C14H16O3S+H 265.0898, found 265.0909.
NMR (400 MHz, CDCl3): d 7.61 (s, 1H), 7.58 (d,
J = 7.8 Hz, 1H), 7.30 (d, J = 7.8 Hz, 1H), 5.76 (ddt,
J = 6.3, 10.0, 18.0 Hz, 1H), 5.02 (dd, J = 1.2, 18.0 Hz,
1H), 4.98 (dd, J = 1.2, 10.0 Hz, 1H), 4.14 (s, 2H), 2.80 (t,
J = 7.3 Hz, 2H), 2.40–2.26 (m, 8H including d 2.34, s, 3H
and d 2.33, s, 3H); 13C NMR (100 MHz, CDCl3): d
197.4, 144.0, 138.1, 135.7, 130.3, 128.7, 128.6, 125.5,
115.6, 66.9, 43.1, 26.9, 19.9, 19.8; HRMS(FAB): calcd for
C14H18O3S+H 267.1055, found 267.1044.
4.17. 1-(2,6-Dimethylphenylsulfonyl)-hex-5-en-2-one
This compound was prepared and purified by the previ-
ously described Procedure A, and was obtained as a white
solid (87%): mp 39–41 ꢁC (hexane/CH2Cl2); IR (KBr) mmax
1718, 926, 832 cmꢀ1; 1H NMR (400 MHz, CDCl3): d 7.42–
7.32 (m, 1H), 7.22–7.14 (m, 2H), 5.77 (ddt, J = 6.8, 10.0,
17.0 Hz, 1H), 5.04 (dd, J = 1.7, 17.0 Hz, 1H), 4.99 (dd,
J = 1.7, 10.0 Hz, 1H), 4.16 (s, 2H), 2.83 (t, J = 7.1 Hz,
2H), 2.67 (s, 6H) 2.33 (dt, J = 6.8, 7.1 Hz. 2H); 13C
NMR (100 MHz, CDCl3): d 197.4, 140.0, 136.0, 135.7,
133.2, 131.6, 115.9, 66.6, 43.8, 27.0, 22.9; HRMS(FAB):
calcd for C14H18O3S+H 267.1055, found 267.1057.
4.21. 1-Diazo-1-(3,4-dimethylphenylsulfonyl)-5-hexen-2-one
11k
This compound was prepared and purified by the previ-
ously described Procedure B, and was obtained as a green-
ish-yellow oil (91%): IR (neat) mmax 1734, 914, 823 cmꢀ1
;
1H NMR (400 MHz, CDCl3): d 7.70 (s, 1H), 7.66 (d,
J = 7.6 Hz, 1H), 7.31 (d, J = 7.6 Hz, 1H), 5.73 (ddt,
J = 6.6, 10.0, 17.0 Hz, 1H), 4.96 (dd, J = 1.5, 17.0 Hz,
1H), 4.92 (dd, J = 1.5, 10.0 Hz, 1H), 2.65 (t, J = 7.6 Hz,
2H), 2.33 (s, 6H), 2.28 (dt, J = 6.6, 7.6 Hz, 2H); 13C
NMR (100 MHz, CDCl3): d 187.4, 143.8, 138.9, 138.1,
135.8, 130.1, 127.6, 124.6, 115.3, 37.8, 27.2, 19.6, 19.5:
HRMS(FAB): calcd for C14H16N2O3S+H 293.0960, found
293.0967.
4.18. 1-Diazo-1-(2,6-dimethylphenylsulfonyl)-5-hexen-2-one
11j
This compound was prepared and purified by the previ-
ously described Procedure B, and was obtained as a green-
ish-yellow solid (83%): IR (KBr) mmax 1671, 913, 832 cmꢀ1
;
4.22. (1R,5R)-1-(3,4-Dimethylphenylsulfonyl)bicyclo[3.1.0]-
hexan-2-one 12k
1H NMR (400 MHz, CDCl3): d 7.43–7.33 (m, 1H), 7.31–
7.18 (m, 2H), 5.66 (ddt, J = 6.8, 11.0, 17.0 Hz, 1H), 4.95
(dd, J = 1.2, 17.0 Hz, 1H), 4.88 (dd, J = 1.2, 11.0 Hz,
1H), 2.70 (s, 6H), 2.50 (t, J = 7.6 Hz, 2H), 2.23 (dt,
J = 6.8, 7.6 Hz, 2H); 13C NMR (100 MHz, CDCl3): d
197.1, 140.1, 137.8, 135.8, 133.3, 130.2, 127.5, 115.8, 37.9,
27.4, 22.6: HRMS(FAB): calcd for C14H16N2O3S+H
293.0960, found 293.0962.
This compound was prepared and purified by the previ-
ously described Procedure C, and was obtained as a white
solid (94%, 72% ee). Ee was determined by HPLC
(254 nm);
Daicel
CHIRALPAK
AS-H
0.46 cm
B · 25 cm; hexane/2-propanol = 4/1; flow rate = 0.5 mL/
min; retention time: 62.0 min for the major enantiomer,
65.0 min for the minor enantiomer; mp 92–94 ꢁC (hex-
28
4.19. (1R,5R)-1-(2,6-Dimethylphenylsulfonyl)bicyclo[3.1.0]-
hexan-2-one 12j
ane/CH2Cl2); ½aꢁD = ꢀ42.3 (c 1.09, CHCl3, 72% ee); IR
(KBr) mmax 1656, 892, 754 cmꢀ1 1H NMR (400 MHz,
;
CDCl3): d 7.78 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.29 (d,
J = 8.0 Hz, 1H), 3.06–2.97 (m, 1H), 2.34 (s, 3H), 2.33 (s,
3H), 2.29–2.13 (m, 4H), 2.10–1.94 (m, 1H), 1.51 (dd,
J = 5.6, 5.6 Hz, 1H); 13C NMR (100 MHz, CDCl3): d
203.5, 143.4, 137.6, 130.0, 129.4, 127.8, 126.2, 53.2, 33.6,
This compound was prepared and purified by the previ-
ously described Procedure C, and was obtained as a white
solid (82%, 91% ee). Ee was determined by HPLC
(254 nm);
Daicel
CHIRALCEL
OD-H
0.46 cm

2904
H. Takeda, M. Nakada / Tetrahedron: Asymmetry 17 (2006) 2896–2906
31.0, 20.3, 20.0, 19.7; HRMS(FAB): calcd for
C14H16O3S+H 265.0898, found 265.0886.
fied by flash chromatography (hexane/ethyl acetate = 4/1)
to afford 15h (323.0 mg, 98%) as a white solid: mp 108–
25
110 ꢁC (hexane/CH2Cl2); ½aꢁD = ꢀ33.0 (c 1.15, CHCl3,
4.23. 1-(3,5-Dimethylphenylsulfonyl)-5-hexen-2-one
93% ee); IR (KBr) mmax 1735, 1457, 844 743 cmꢀ1 1H
;
NMR (400 MHz, CDCl3): d 7.82 (d, J = 8.0 Hz, 1H),
7.48 (d, J = 7.6 Hz, 1H), 7.31 (dd, J = 7.6, 8.0 Hz, 1H),
3.76 (d, J = 9.8 Hz, 1H), 3.37–3.23 (m, 1H), 3.00 (dd,
J = 5.8, 17.0 Hz, 1H), 2.81 (dd, J = 3.8, 17.0 Hz, 1H),
2.66–2.28 (m, 9H including d 2.60, s, 3H and d 2.37, s,
3H), 1.88–1.73 (m, 1H); 13C NMR (100 MHz, CDCl3): d
203.8, 139.8, 136.6, 136.1, 135.9, 129.2, 125.8, 116.9, 70.9,
38.7, 34.1, 25.7, 22.3, 20.5, 16.3; HRMS(FAB): calcd for
C15H17NO3S+H 292.1007, found 292.1017.
This compound was prepared and purified by the previ-
ously described Procedure A, and was obtained as a color-
less oil (98%): IR (neat) mmax 1720, 730, 684 cmꢀ1 1H
;
NMR (400 MHz, CDCl3): d 7.47 (s, 2H), 7.28 (s, 1H),
5.76 (ddt, J = 6.8, 10.0, 17.0 Hz, 1H), 5.03 (dd, J = 1.2,
17.0 Hz, 1H), 4.99 (dd, J = 1.2, 10.0 Hz, 1H), 4.13 (s,
2H), 2.81 (t, J = 7.3 Hz, 2H), 2.39 (s, 6H), 2.32 (dt,
J = 6.8, 7.3 Hz, 2H); 13C NMR (100 MHz, CDCl3): d
197.3, 139.4, 138.3, 136.1, 135.9, 125.5, 115.7, 67.0, 43.2,
27.0, 21.1; HRMS(FAB): calcd for C14H18O3S+H
267.1055, found 267.1052.
4.27. (R)-(3-Oxocyclopentyl)acetonitrile (16)
Compound 16 was obtained from 12e–l according to the
4.24. 1-Diazo-1-(3,5-dimethylphenylsulfonyl)-5-hexen-2-one
11l
procedure in Ref. 6.
Compound 16 was obtained from 12e in 55% yield (2
24
This compound was prepared and purified by the previ-
steps): ½aꢁD = ꢀ70.1 (c 1.20, CHCl3, >99% ee).
ously described Procedure B, and was obtained as a green-
ish-yellow oil (90%): IR (neat) mmax 1734, 858, 786 cmꢀ1
;
Compound 16 was obtained from 12f in 49% yield (2
23
1H NMR (400 MHz, CDCl3): d 7.55 (s, 2H), 7.28 (s, 1H),
5.72 (ddt, J = 6.3, 9.8, 16.0 Hz, 1H), 4.97 (dd, J = 1.2,
16.0 Hz, 1H), 4.93 (dd, J = 1.2, 9.8 Hz, 1H), 2.66 (t,
J = 7.6 Hz, 2H), 2.41 (s, 6H), 2.30 (dt, J = 6.3, 7.6 Hz,
2H); 13C NMR (100 MHz, CDCl3): d 197.2, 141.8, 139.7,
136.1, 135.8, 124.6, 115.7, 38.1, 27.5, 21.2, 14.1:
HRMS(FAB): calcd for C14H16N2O3S+H 293.0960, found
293.0962.
steps). ½aꢁD = ꢀ70.0 (c 1.20, CHCl3, >99% ee).
Compound 16 was obtained from 12g in 56% yield (2
26
steps). ½aꢁD = ꢀ69.9 (c 1.20, CHCl3, >99% ee).
Compound 16 was obtained from 12h in 55% yield (2
27
steps). ½aꢁD = ꢀ70.2 (c 1.20, CHCl3, >99% ee).
Compound 16 was obtained from 12i in 51% yield (2 steps).
24
4.25. (1R,5R)-1-(3,5-Dimethylphenylsulfonyl)bicyclo[3.1.0]-
hexan-2-one 12l
½aꢁD = ꢀ70.1 (c 1.20, CHCl3, >99% ee).
Compound 16 was obtained from 12j in 51% yield (2 steps).
28
This compound was prepared and purified by the previ-
ously described Procedure C, and was obtained as a white
solid (91%, 62% ee). Ee was determined by HPLC
½aꢁD = ꢀ69.9 (c 1.20, CHCl3, >99% ee).
Compound 16 was obtained from 12k in 50% yield (2
steps). ½aꢁD = ꢀ70.0 (c 1.20, CHCl3, >99% ee).
26
(254 nm);
Daicel
CHIRALPAK
AS-H
0.46 cm
B · 25 cm; hexane/2-propanol = 4/1; flow rate = 0.5 mL/
min; retention time: 33.0 min for the major enantiomer,
Compound 16 was obtained from 12l in 54% yield (2 steps).
25
35.0 min for the minor enantiomer; mp 95–97 ꢁC (hex-
½aꢁD = ꢀ70.1 (c 1.20, CHCl3, >99% ee).
28
ane/CH2Cl2); ½aꢁD = ꢀ41.0 (c 1.37, CHCl3, 62% ee); IR
(KBr) mmax 1716, 982, 882 cmꢀ1
;
1H NMR (400 MHz,
4.28. (1R,2RS)-[2-(2,3-Dimethylbenzenesulfonyl)-2-methyl-
3-oxocyclopentyl]acetonitrile (17C); (R)-[2-(2,3-dimethyl-
benzenesulfonyl)-3-methoxy-2-cyclopentenyl]acetonitrile
17O
CDCl3): d 7.64 (s, 2H), 7.26 (s, 1H), 3.07–2.99 (m, 1H),
2.40 (s, 6H), 2.38–2.15 (m, 4H), 2.11–1.98 (m, 1H), 1.53
(dd, J = 5.4, 5.4 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 203.4, 139.1, 138.8, 135.5, 126.2, 53.1, 33.6, 31.0, 21.2,
20.3; HRMS(FAB): calcd for C14H16O3S+H 265.0898,
found 265.0900.
To a solution of 15h (100 mg, 0.343 mmol) in DMF (3 mL)
were added potassium carbonate (71.0 mg, 0.514 mmol)
and methyl iodide (0.064 mL, 1.03 mmol) successively,
and the reaction mixture was stirred at room temperature
for 2 h. The reaction mixture was quenched with saturated
aqueous NH4Cl solution (10 mL) and extracted with ether
(3 mL · 2). The combined organic layer was washed with
brine (5 mL), dried over Na2SO4, and evaporated. The res-
idue was purified by flash chromatography (hexane/ethyl
acetate = 4/1) to afford 17C (69.1 mg, 66%, dr = 5:1) as a
white solid and 17O (28.2 mg, 27%) as a white solid.
4.26. (1R,2R)-[2-(2,3-Dimethylbenzenesulfonyl)-3-oxocyclo-
pentyl]acetonitrile 15h
To a solution of 12h (300.0 mg, 1.13 mmol) in DMSO
(10 mL) was added sodium cyanide (61.2 mg, 1.25 mmol)
and the reaction mixture was stirred at 80 ꢁC for 5 h. After
the starting material disappeared, the reaction mixture was
quenched with saturated aqueous NaHCO3 solution
(10 mL) and extracted with ethyl acetate (3 mL · 2). The
combined organic layer was washed with brine (5 mL),
dried over Na2SO4, and evaporated. The residue was puri-
Compound 17C: IR (KBr) mmax 1751, 1461, 919, 835 cmꢀ1
1H NMR (400 MHz, CDCl3): major product: d 7.68 (d,
;

H. Takeda, M. Nakada / Tetrahedron: Asymmetry 17 (2006) 2896–2906
2905
J = 8.1 Hz, 1H), 7.44 (d, J = 7.3 Hz, 1H), 7.32–7.26 (m,
1H), 3.51–3.40 (m, 1H), 2.92 (dd, J = 4.4, 17.0 Hz, 1H),
2.89–2.28 (m, 10H including d 2.48, s, 3H and d 2.33, s,
3H), 1.72–1.56 (m, 1H), 1.27 (s, 3H); minor product: d
7.61 (d, J = 8.1 Hz, 1H), 7.44 (d, J = 7.3 Hz, 1H), 7.32–
7.26 (m, 1H), 3.51–3.40 (m, 1H), 2.92 (dd, J = 4.4,
17.0 Hz, 1H), 2.89–2.28 (m, 10H including d 2.48, s, 3H
and d 2.33, s, 3H), 1.72–1.56 (m, 1H), 1.30 (s, 3H);
HRMS(FAB): calcd for C16H19NO3S+H 306.1164, found
306.1150.
J = 3.9, 17.0 Hz, 1H), 2.64–2.39 (m, 6H including d 2.52,
s, 3H), 2.38–2.19 (m, 4H including d 2.33, s, 3H), 1.90
(dddd, J = 3.4, 7.8, 9.0, 9.7 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d 165.9, 140.0, 139.1, 136.5, 134.7,
127.2, 125.5, 118.3, 114.3, 76.9, 76.8, 58.0, 39.8, 29.1,
25.7, 23.3, 20.4, 16.0; HRMS(FAB): calcd for
C18H19NO3S+H 330.1164, found 330.1150.
Acknowledgments
Compound 17O: mp 113–115 ꢁC (CH2Cl2–hexane);
This work was financially supported in part by a Waseda
University Grant for Special Research Projects and a
Grant-in-Aid for Scientific Research on Priority Areas
(Creation of Biologically Functional Molecules (No.
17035082)) from The Ministry of Education, Culture,
Sports, Science, and Technology (MEXT), Japan. We are
also indebted to 21COE ‘Practical Nano-Chemistry’.
25
½aꢁD = ꢀ17.9 (c 0.72, CHCl3, 93% ee); IR (KBr) mmax
1
1457, 946, 801 cmꢀ1; H NMR (400 MHz, CDCl3): d 7.89
(d, J = 7.8 Hz, 1H), 7.37 (d, J = 7.3 Hz, 1H), 7.25 (dd,
J = 7.3, 7.8 Hz, 1H), 3.75 (s, 3H), 3.30–3.20 (m, 1H), 2.77
(dd, J = 3.6, 17.0 Hz, 1H), 2.70–2.45 (m, 6H including d
2.52, s, 3H), 2.48–2.20 (m, 4H including d 2.33, s, 3H),
1.97–1.83 (m, 1H); 13C NMR (100 MHz, CDCl3): d
168.5, 140.2, 139.1, 136.3, 134.6, 127.0, 125.4, 118.4,
111.3, 58.2, 40.0, 29.2, 25.5, 23.4, 20.4, 15.8; HRMS(FAB):
calcd for C16H19NO3S+H 306.1164, found 306.1161.
References
1. Honma, M.; Sawada, T.; Fujisawa, Y.; Utsugi, M.; Watan-
abe, H.; Umino, A.; Matsumura, T.; Hagihara, T.; Takano,
M.; Nakada, M. J. Am. Chem. Soc. 2003, 125, 2860–2861.
2. Reviews for the preparation and use of cyclopropanes: (a)
Wong, H. N. C.; Hon, M.-Y.; Tse, C.-W.; Yip, Y.-C.; Tanko,
J.; Hudlicky, T. Chem. Rev. 1989, 89, 165–198; (b) Davies, H.
M. L. In Comprehensive Organic Synthesis; Trost, B. M.,
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3. Honma, M.; Nakada, M. Tetrahedron Lett. 2003, 44, 9007–
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4. For the catalytic asymmetric synthesis of bicyclo[3.1.0]hexa-
none derivatives with a phenyl group at the bridgehead
position, see: Sawada, T.; Nakada, M. Adv. Synth. Catal.
2005, 347, 1527–1532.
4.29. (1R,2RS)-[2-(2,3-Dimethylbenzenesulfonyl)-3-oxo-2-
(2-propynyl)cyclopentyl]acetonitrile (18C); (R)-[2-(2,3-di-
methylbenzenesulfonyl)-3-(2-propynyloxy)-2-cyclopentenyl]-
acetonitrile 18O
To a solution of 15h (100.0 mg, 0.343 mmol) in DMF
(2 mL) were added potassium carbonate (71.0 mg,
0.514 mmol), sodium iodide (154.0 mg, 1.03 mmol), and
propargyl bromide (0.094 mL, 1.03 mmol) successively,
and the reaction mixture was stirred at room temperature
for 3 h. The reaction mixture was quenched with saturated
aqueous NH4Cl solution (3 mL) and extracted with ether
(1 mL · 2). The combined organic layer was washed with
brine (5 mL), dried over Na2SO4, and evaporated. The res-
idue was purified by flash chromatography (hexane/ethyl
acetate = 4/1) to afford 18C (65.5 mg, 58%, dr = 10:1)
and 18O as white solids (37.2 mg, 33%).
5. Takano, M.; Umino, A.; Nakada, M. Org. Lett. 2004, 6,
4897–4900.
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Compound 18C: IR (KBr) mmax 2262, 1660, 832, 767 cmꢀ1
;
1H NMR (400 MHz, CDCl3): major product: d 7.68 (d,
J = 8.0 Hz, 1H), 7.49 (d, J = 7.3 Hz, 1H), 7.28 (dd,
J = 7.3, 8.0 Hz, 1H), 3.67–3.54 (m, 1H), 3.06–2.90 (m,
2H), 2.83 (dd, J = 2.6, 17.0 Hz, 1H), 2.67–2.30 (m, 10H,
including d 2.49, s, 3H and d 2.36, s, 3H), 2.08 (dd,
J = 2.6, 2.6 Hz, 1H), 2.01–1.88 (m, 1H); minor product: d
7.62 (d, J = 8.0 Hz, 1H), 7.49 (d, J = 7.3 Hz, 1H), 7.28
(dd, J = 7.3, 8.0 Hz, 1H), 3.67–3.54 (m, 1H), 3.06–2.90
(m, 2H), 2.67–2.30 (m, 11H including d 2.60, dd, J = 2.5,
17.0 Hz, 1H and d 2.49, s, 3H and d 2.34, s, 3H), 2.06
(dd, J = 2.5, 2.5 Hz, 1H), 2.01–1.88 (m, 1H);
HRMS(FAB): calcd for C18H19NO3S+H 330.1164, found
330.1161.
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Fahndrich, B.; Pfaltz, A. Synlett 1995, 491–492; (c) Park,
S.-W.; Son, J.-H.; Kim, S.-G.; Ahn, K. H. Tetrahedron:
Asymmetry 1999, 10, 1903–1911; (d) Kim, S. G.; Cho, C. W.;
Ahn, K. H. Tetrahedron 1999, 55, 10079–10086; (e) Barberis,
M.; Estevan, F.; Lahuerta, P.; Perez-Prieto, J.; Sanau, M.
Inorg. Chem. 2001, 40, 4226–4229; (f) Barberis, M.; Perez-
Prieto, J.; Stiriba, S.-E.; Lahuerta, P. Org. Lett. 2001, 3,
3317–3319; (g) Saha, B.; Uchida, T.; Katsuki, T. Chem. Lett.
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Saha, B.; Uchida, T.; Katsuki, T. Tetrahedron: Asymmetry
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Estevan, F.; Lahuerta, P.; Lloret, J.; Perez-Prieto, J.; Werner,
H. Organometallics 2004, 23, 1369–1372; (l) Estevan, F.;
Compound 18O: mp 119–121 ꢁC (CH2Cl2–hexane);
25
½aꢁD = ꢀ11.2 (c 0.94, CHCl3, 93% ee); IR (KBr) mmax
1
2124, 1454, 792, 709 cmꢀ1; H NMR (400 MHz, CDCl3):
d 7.91 (d, J = 8.0 Hz, 1H), 7.37 (d, J = 7.6 Hz, 1H), 7.24
(dd, J = 7.6, 8.0 Hz, 1H), 4.50 (d, J = 2.2 Hz, 2H), 3.32–
3.23 (m, 1H), 2.86–2.71 (m, 2H including d 2.81, dd,

2906
H. Takeda, M. Nakada / Tetrahedron: Asymmetry 17 (2006) 2896–2906
Lahuerta, P.; Lloret, J.; Penno, D.; Sanau, M.; Ubeda, M. A.
J. Organomet. Chem. 2005, 690, 4424–4432; (m) Uchida, T.;
Katsuki, T. Synthesis 2006, 10, 1715–1723.
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1985, 50, 3334–3336; (b) Beaulieu, C.; Guay, D.; Wang, Z.;
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9. For the attempted catalytic asymmetric IMCP reaction of the
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Muhler, P.; Bolea, C. Helv. Chim. Acta 2001, 84, 1093–
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1111.