A synthesis of bicyclo[n.1.0]alkanes having tert-butyl carboxylate or acetamide moiety via the intramolecular 1,3-CH insertion of magnesium carbenoids

Article abstract of DOI:10.1016/j.tet.2008.04.024

Treatment of 1-chlorovinyl p-tolyl sulfoxides, derived from various cyclic ketones and chloromethyl p-tolyl sulfoxide, with lithium enolate of carboxylic acid tert-butyl esters or N,N-dimethylacetamide gave adducts in high yields. The adducts were treated with ether solution of isopropylmagnesium chloride in dry toluene to give bicyclo[n.1.0]alkane derivatives having tert-butyl carboxylate or acetamide moiety on the bridgehead carbon in high to quantitative yields via magnesium carbenoid 1,3-CH insertion reaction. The 1,3-CH insertion reaction proved to be regioselective and stereospecific. The reaction mechanism and origin of the selectivity and specificity are discussed.

Full text of DOI:10.1016/j.tet.2008.04.024

Tetrahedron 64 (2008) 5711–5720
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A synthesis of bicyclo[n.1.0]alkanes having tert-butyl carboxylate or acetamide
moiety via the intramolecular 1,3-CH insertion of magnesium carbenoids
*
Shingo Ogata, Hideki Saitoh, Daisuke Wakasugi, Tsuyoshi Satoh
Department of Chemistry, Faculty of Science, Tokyo University of Science, Ichigaya-funagawara-machi 12, Shinjuku-ku, Tokyo 162-0826, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Treatment of 1-chlorovinyl p-tolyl sulfoxides, derived from various cyclic ketones and chloromethyl p-
tolyl sulfoxide, with lithium enolate of carboxylic acid tert-butyl esters or N,N-dimethylacetamide gave
adducts in high yields. The adducts were treated with ether solution of isopropylmagnesium chloride in
dry toluene to give bicyclo[n.1.0]alkane derivatives having tert-butyl carboxylate or acetamide moiety on
the bridgehead carbon in high to quantitative yields via magnesium carbenoid 1,3-CH insertion reaction.
The 1,3-CH insertion reaction proved to be regioselective and stereospecific. The reaction mechanism and
origin of the selectivity and specificity are discussed.
Received 17 March 2008
Received in revised form 5 April 2008
Accepted 7 April 2008
Available online 10 April 2008
Keywords:
Cyclopropane
Bicyclo[n.1.0]alkane
Magnesium carbenoid
C–H insertion
Ó 2008 Elsevier Ltd. All rights reserved.
Sulfoxide-magnesium exchange
1. Introduction
cyclic ketones 1, chloromethyl p-tolyl sulfoxide 2, and carboxylic
acid derivatives 4. Thus, 1-chlorovinyl p-tolyl sulfoxides
3
Carbenes and carbenoids have long been recognized to be highly
reactive carbon species and are frequently used as versatile in-
termediates in organic synthesis.1 The carbon–hydrogen insertion
(CH insertion) is one of the most striking reactions of carbenes and
carbenoids.2 The CH insertion reaction is very interesting and
highly useful for construction of molecules, because the reaction
enables the formation of a carbon–carbon bond between a carbene
(or carbenoid) carbon and a non-activated carbon.
were easily synthesized in three steps from cyclic ketones 1 and
chloromethyl p-tolyl sulfoxide 2 in high overall yields.6 Conjugate
addition of lithium enolate of tert-butyl carboxylate or N,N-dime-
thylacetamide 4 gave the adducts 5 in high yields.7 Treatment of the
adducts 5 with i-PrMgCl afforded bicyclo[n.1.0]alkane derivatives 7
in high yields via magnesium carbenoid intermediates 6. Details of
these reactions and some discussions for the mechanism of the
reactions are described.
Previously, we found that the magnesium carbenoids, generated
from aryl 1-chloroalkyl sulfoxides with Grignard reagents via the
sulfoxide–magnesium exchange reaction, were stable below
ꢀ60 ꢁC for at least 30 min.3 Quite interestingly, when the carbon
adjacent to the magnesium carbenoid carbon was quaternary, 1,3-
CH insertion took place to afford cyclopropanes in high to quanti-
tative yields upon warming the reaction mixture to 0 ꢁC.4
2. Results and discussion
2.1. Synthesis of bicyclo[n.1.0]alkane derivatives having tert-
butyl carboxylate moiety on the bridgehead carbon and some
mechanistic studies of the reactions
In continuation of our interest in the chemistry of the magne-
sium carbenoid 1,3-CH insertion reaction, we recently investigated
the reaction of 1-chloroalkyl p-tolyl sulfoxides 5 with i-PrMgCl and
found that the reaction resulted in the formation of bicyclo-
[n.1.0]alkane derivatives 7 in high yields (Scheme 1).5 As shown in
Scheme 1, this method is very useful for a synthesis of bicyclo-
[n.1.0]alkane derivatives 7 by assemblage of three components,
At first, 1-chlorovinyl p-tolyl sulfoxide 8 was synthesized from
cyclopentadecanone6 and was treated with the lithium enolate of
tert-butyl acetate to give adduct 9 in a quantitative yield (Scheme
2).7 A solution of the adduct 9 in toluene was added to a solution of
i-PrMgCl (in ether) in dry toluene at ꢀ78 ꢁC dropwise with stirring.
The temperature of the reaction mixture was slowly allowed to
warm to 0 ꢁC for 2 h to give bicyclo[13.1.0]hexadecane having tert-
butyl acetate moiety on the bridgehead carbon 11 in 96% yield via
magnesium carbenoid intermediate 10. As reported in the pre-
liminary communication,5 using i-PrMgCl in ether and toluene as
the reaction solvent was found to be essential to this reaction.
* Corresponding author.
E-mail address: tsatoh@rs.kagu.tus.ac.jp (T. Satoh).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.04.024

5712
S. Ogata et al. / Tetrahedron 64 (2008) 5711–5720
R1CH2COX
4
TolS(O)CH2Cl
2
Cl
S(O)Tol
Cl
S(O)Tol
O
in three steps
LDA
m
CHCOX
R1
5
m
m
R1 = H, Alkyl
t
1
3
X = O Bu, NMe2
H
Cl
Magnesium carbenoid
MgCl 1,3-CH insertion
i-PrMgCl (in Et2O)
Toluene, -78 ~ 0 °C
CHCOX
R1
m
CHCOX
R1
m
7
6
bicyclo[n.1.0]alkane
Scheme 1.
Cl
Cl
H
S(O)Tol
MgCl
t
S(O)Tol
15
i-PrMgCl (in Et2O)
LiCH2COO Bu
98%
Toluene, -78 ~ 0 °C
t
t
Cl
CH2COO Bu
CH2COO Bu
10
9
8
1,3-CH insertion
96%
t
t
CHCOO Bu
CH2COO Bu
11
12
Scheme 2.
The magnesium carbenoid 1,3-CH insertion reaction was
expected to take place between the carbenoid carbon and the
methylene carbon on the cyclopentadecane ring (giving cyclopro-
pane 11) or the methylene carbon adjacent to the carbonyl carbon
(giving spiro-type cyclopropane 12). In this reaction, cyclopropane
11 was obtained as a single product and no spiro-type cyclopropane
12 was observed. Namely, this reaction was highly regioselective. In
addition, in the case of cyclopropane 11, E- or Z-isomer could be
formed. At present, E-isomer is anticipated as the product 11.
Stereoselectivity of this reaction was also high. The regioselectivity
and the stereoselectivity of this reaction will be discussed later.
We next investigated the generality of this reaction and the
results are summarized in Table 1. The reaction starting from 1-
chlorovinyl p-tolyl sulfoxides derived from cyclopentanone and
cyclohexanone (13a and 13b) gave 15a and 15b, respectively, in
good overall yields via adducts 14a and 14b. In the case of 1-
chlorovinyl p-tolyl sulfoxide derived from cyclohexane-1,4-dione
mono ethylene ketal (13c), the addition reaction gave 14c as
a mixture of separable two diastereomers (entry 3). These adducts
were separately treated with i-PrMgCl to afford the same cyclo-
propane 15c both in high yields. This procedure starting from
medium-sized cycloalkanone (cyclooctanone and cyclodecanone)
gave the desired cyclopropanes 15d and 15e in good overall yields
(entries 4 and 5). Interestingly, all the produced bicyclo[n.1.0]alkane
derivatives 15 were single isomers, except one case (entry 5). Ob-
viously, the product 15e is a mixture of E- and Z-isomers with re-
spect to the configuration of the cyclopropane ring.
The results using tert-butyl propionate, tert-butyl hexanoate,
and tert-butyl 4-phenylbutyrate as the ester component are sum-
marized in Table 2. Because the reaction of 1-chlorovinyl p-tolyl
sulfoxides with lithium enolate of tert-butyl carboxylate is highly
stereoselective,8 all the adducts 16 were obtained as a single
product in good to quantitative yields. Generation of the magne-
sium carbenoids from 16 was carried out under the same condi-
tions as described above to give bicyclo[n.1.0]alkane derivatives 17
in high yield. Interestingly, when 13a was used as the starting vinyl
Table 1
Synthesis of bicyclo[n.1.0]alkane derivatives having tert-butyl acetate moiety 15 from 1-chlorovinyl p-tolyl sulfoxides 13 via adducts 14
Cl
S(O)Tol
t
S(O)Tol
Cl
i-PrMgCl / Et2O
Toluene
-78 ~ 0 °C, 2 h
CH3COO Bu
LDA / THF
-78 °C, 5 min
t
t
CH2COO Bu
m
m
CH2COO Bu
m
13
14
15
Entry
13
14, Yield %
15, Yield %
m
1
2
13a
13b
1
2
98
97
74
89
O
Cl
(L) 86a
(P) 14a
(L) 95b
(P) 93c
3
13c
S(O)Tol
O
4
5
13d
13e
4
6
97
96
90
77d
a
The adduct 14c was obtained as a mixture of separable two diastereomers (less polar adduct (86%) and more polar adduct (14%)).
The yield from the adduct 14c-L.
The yield from the adduct 14c-P.
b
c
d
The product 15e was obtained as a mixture of two inseparable diastereomers (ratio about 2:1).

S. Ogata et al. / Tetrahedron 64 (2008) 5711–5720
5713
Table 2
Synthesis of bicyclo[n.1.0]alkane derivatives having tert-butyl carboxylate moiety 17 from 1-chlorovinyl p-tolyl sulfoxides 13 via adducts 16
Cl
t
S(O)Tol
RCH2COO Bu
i-PrMgCl / Et2O
S(O)Tol
Cl
t
LDA / THF
Toluene
-78 ~ 0 °C, 2 h
t
CHCOO Bu
m
m
CHCOO Bu
m
-78 °C, 5 min
R
R
16
17
Entry
1
1-Chlorovinyl p-tolyl sulfoxide
R
16,a Yield %
17, Yield %
17a, 94b
m
13a
13b
1
2
PhCH2CH2
CH3
CH3(CH2)3
PhCH2CH2
16a, 60
2
3
4
16b, 99
16c, 99
16d, 99
17b, 76c
17c, 95c
17d, 89c
5
6
13d
4
CH3
CH3(CH2)3
16e, 88
16f, 78
17e, 96c
17f, 89c
a
All adducts 16 were obtained as a single isomer.
About 5:1 mixture of two diastereomers.
Single isomer.
b
c
sulfoxide, the product 17a was obtained as a mixture of two di-
astereomers (entry 1). All other products 17 were obtained as single
product (entries 2–6).
lithium enolate of tert-butyl carboxylate is highly stereo-
selective.8,9 Thus, the adducts 19a and 19b, derived from 18a and
18b, respectively, have relative stereochemistry as shown in
Scheme 4. We propose a six-membered transition state model A
for the 1,3-CH insertion reaction of the magnesium carbenoid
intermediate derived from adduct 19a with i-PrMgCl.9 In this
transition state, C–H bond on the methylene carbon of the
cyclohexene ring could attack the chlorine atom from its back-
side to give smoothly cyclopropane 20a. On the other hand,
magnesium carbenoid intermediate derived from 18b would
form a six-membered transition state B. Because the bond placed
on backside of the chlorine atom is between olefinic carbon and
hydrogen, the CH insertion should not take place and the mag-
nesium carbenoid intermediate would decompose upon
warming.
These transition state models also explain the reason why the
CH insertion does not take place between the carbenoid carbon and
the methylene carbon adjacent to the carbonyl carbon as men-
tioned before. In these transition states, attack of both the C–H
bonds on the methylene carbon adjacent to the carbonyl carbon to
the chlorine atom from backside is impossible.
The results were quite similar with the reactions starting from
18c and 18d (entries 3 and 4). Treatment of the adduct 19c derived
from E-vinyl sulfoxide 18c with i-PrMgCl gave cyclopropane 20c
and the same transition state model can be applied to this reaction.
On the other hand, the reaction of the adduct 19d, derived from Z-
vinyl sulfoxide 18d, with i-PrMgCl didn’t give a cyclopropane but
isopropylated product 20d. The alkylation of the magnesium car-
benoid intermediate with i-PrMgCl was thought to occur in this
particular case.3
It is already well established that the addition reaction of 1-
chlorovinyl p-tolyl sulfoxides with the lithium enolate of tert-butyl
carboxylate is highly stereoselective.8,9 In the case of the present
study, the adduct 16a has relative stereochemistry as shown in
Scheme 3. As the epimerization of the stereogenic center bearing
the alkyl substituent is quite unlikely under the conditions, the
stereoselectivity of the 1,3-CH insertion reaction of the carbenoid
derived from 16a is thought to be low to afford a mixture of 17A and
17B shown in Scheme 3. On the other hand, stereoselectivity of the
1,3-CH insertion reaction of the magnesium carbenoid derived
from other adducts 16b–16f proved to be high.
The results of the procedure starting from unsymmetrical ke-
tones are summarized in Table 3. As shown in Table 3, quite in-
teresting specificity was observed. Thus, at first, geometrical
isomers of the 1-chlorovinyl p-tolyl sulfoxides 18a and 18b were
synthesized from 2-cyclohexenone in high overall yields.7c The E-
isomer 18a was treated with the lithium enolate of tert-butyl ace-
tate to give adduct 19a, which was treated with i-PrMgCl to afford
cyclopropane 20a in 90% yield (entry 1). Very interestingly, when
the adduct 19b, derived from Z-geometrical isomer 18b with the
lithium enolate of tert-butyl acetate, was treated with i-PrMgCl
only a complex mixture was obtained (entry 2). Namely, the mag-
nesium carbenoid 1,3-CH insertion reaction is thought to be highly
stereospecific.
The situation was quite similar in the reactions starting from
a
-tetralone (entries 3 and 4). Thus, E-vinyl sulfoxide 18c gave the
desired cyclopropane 20c through adduct 19c. However, the re-
action starting from Z-vinyl sulfoxide 18d gave alkylated product
20d.3 In addition, the reaction starting from vinyl sulfoxide 18e,
which was derived from 1-indanone, gave one-carbon ring-ex-
panded product 20e (entry 5).
The specificity of this reaction mentioned above can be
explained as follows (Scheme 4). As already mentioned above,
the addition reaction of 1-chlorovinyl p-tolyl sulfoxides with the
Interesting one-carbon ring-expansion reaction was observed in
the reaction starting from 1-chlorovinyl p-tolyl sulfoxide derived
from 1-indanone (18e, entry 5). Thus, treatment of adduct 19e,
derived from 18e in a quantitative yield, with i-PrMgCl gave dihy-
dronaphthalene derivative 20e in 69% yield. Magnesium carbenoid
1,2-CC insertion reaction is expected to occur in this relatively
strained five-membered ring.
H
Cl
S*
t
S(O)Tol
S*
RCH2COO Bu
S(O)Tol
Cl
i-PrMgCl / Et2O
Toluene
t
R*
CCOO Bu
+
LDA / THF
t
t
CCOO Bu
CCOO Bu
S*
H
S*
H
H
R
13a
R
R
17B
16a
17A
Scheme 3.

5714
S. Ogata et al. / Tetrahedron 64 (2008) 5711–5720
Table 3
Reaction of 1-chlorovinyl p-tolyl sulfoxides 18 derived from unsymmetrical ketones with lithium enolate of tert-butyl acetate followed by i-PrMgCl
Cl
R1
R2
R1
R2
t
S(O)Tol
CH3COO Bu
LDA / THF
-78 ~ -40 °C, 1 h
S(O)Tol
Cl
i-PrMgCl / Et2O
Toluene
-78 ~ 0 °C, 2 h
Product 20
t
CH2COO Bu
19
18
Entry
1-Chlorovinyl p-tolyl sulfoxide 18
19, Yield %
Product 20
Yield %
90
Cl
1
2
18a
18b
(E)
(Z)
19a, 96
19b, 98
20a
t
CH2COO Bu
S(O)Tol
S(O)Tol
Cl
Complete mixture
d
Cl
t
CH2COO Bu
S(O)Tol
3
4
18c
18d
(E)
(Z)
19c, 53
19d, 95
20c
20d
57
S(O)Tol
Cl
da
t
CH2COO Bu
S(O)Tol
Cl
t
CH2COO Bu
5
18e
19e, 99
20e
69
a
A product containing inseparable unknown compounds.
2.2. Asymmetric synthesis of bicyclo[4.1.0]hept-2-ene having
tert-butyl acetate moiety
sulfoxide.10 The vinyl sulfoxide was treated with lithium enolate of
tert-butyl acetate to afford adduct (ꢀ)-19a in 96% yield. The abso-
lute configuration and optical purity of (ꢀ)-19a had been estab-
lished already.7c Finally, (ꢀ)-19a was treated with i-PrMgCl under
the same conditions described above to give optically pure (1S,6R)-
As an application of the presented method, an asymmetric
synthesis of optically active bicyclo[4.1.0]hept-2-ene having acetic
ester moiety on the bridgehead carbon was investigated as follows
(Scheme 5). At first, optically active vinyl sulfoxide (þ)-18a7c was
synthesized from 2-cyclohexenone and (R)-chloromethyl p-tolyl
bicyclo[4.1.0]hept-2-en-1-ylacetic acid tert-butyl ester (þ)-20a
28
([a
]
þ137.2 (c 0.1, EtOH)) in 90% yield.
D
O
S*
(R)
O
S
S
S(O)Tol
R*
Tol
Tol
ClH2C
t
t
LiCH2COO Bu
BuOOC
O
Cl
3 steps (lit. 7c)
Cl
Cl
96%
t
S*
LiCH2COO Bu
i-PrMgC
l
(+)-18a
S(O)Tol
S*
H
H
19a
Cl
H
18a
S(O)Tol
(S)(R)
H
i-PrMgCl / Et2O
(S)
H
t
t
Toluene, -78 ~ 0 °C
90%
CH2COO Bu
CH2COO Bu
(R)
t
CH-insertion
H
Bu
O
(-)-19a
t
Mg
(+)-20a
COO Bu
H
O
Cl
20a
Scheme 5.
Cl
A
S*
S(O)Tol
R*
2.3. Synthesis of bicyclo[n.1.0]alkane derivatives having
N,N-dimethylacetamide moiety on the bridgehead carbon
t
Bu
OOC
S*
Cl
t
S(O)Tol
Cl
R*
LiCH2COO Bu
i-PrMgCl
Finally, as an extension of this synthetic method, we in-
vestigated an availability of N,N-dimethylacetamide, instead of tert-
butyl carboxylate, in this procedure and the results are summarized
in Table 4. At first, 1-chlorovinyl p-tolyl sulfoxides having various
ring size were synthesized and the reaction with the lithium eno-
late of N,N-dimethylacetamide was studied.7b As shown in Table 4,
the yields for adducts 21 are usually very good except for m¼1 and
4 (entries 1 and 4). Especially, the addition reaction with 1-chloro-
vinyl p-tolyl sulfoxide derived from cyclooctanone (13d) was very
low. However, the reason for the low yield is still obscure.
19b
18b
H
No CH-insertion
occurs
t
Bu
O
Complex mixture
Mg
H
O
Cl
Cl
B
Scheme 4.

S. Ogata et al. / Tetrahedron 64 (2008) 5711–5720
5715
Table 4
Synthesis of bicyclo[n.1.0]alkane derivatives having N,N-dimethylacetamide moiety 22 from 1-chlorovinyl p-tolyl sulfoxides via adducts 21
Cl
S(O)Tol
S(O)Tol
Cl
i-PrMgCl / Et2O
Toluene
-78 ~ 0 °C, 2 h
CH3CONMe2
CH2CONMe2
LDA / THF
-78 ~ -50 °C,
40 min
m
m
CH2CONMe2
m
21
22
Entry
1-Chlorovinyl p-tolyl sulfoxide
21, Yield %
22, Yield %
(diastereomeric ratio)
m
1
2
3
4
5
6
13a
13b
13f
13d
13g
8
1
2
3
4
8
21a, 57 (9:1)
21b, 99 (5:4)
21c, 99 (19:1)
21d, 22 (14:1)
21e, 99(13:1)
21f, 99 (10:1)
22a, 93
22b, 99
22c, 73
22d, 92
22e, 84a
22f, 88a
11
a
A 3:1 mixture of two geometrical isomers.
Treatment of the adducts 21 with i-PrMgCl was investigated
under the same conditions as described above. Fortunately, the 1,3-
CH insertion reaction of the generated magnesium carbenoids
proceeded smoothly to afford the desired bicyclo[n.1.0]alkanes
having N,N-dimethylacetamide moiety on the bridgehead carbon
from 73 to 99% yields. Interestingly, the bicyclo[n.1.0]alkanes 22
having a large-sized ring (12- and 18-membered ring) were
obtained as a mixture of two geometrical isomers (entries 5 and 6).
In conclusion, we have developed a new method for a synthesis
of bicyclo[n.1.0]alkanes having tert-butyl carboxylate or N,N-
dimethylacetamide moiety on the bridgehead carbon by assem-
blage of three components, cyclic ketones 1, chloromethyl p-tolyl
sulfoxide 2, and carboxylic acid derivatives 4 with magnesium
carbenoid 1,3-CH insertion as the key reaction in relatively short
step. We believe that the magnesium carbenoid 1,3-CH insertion
reaction will be used widely in the synthesis of cyclopropane
derivatives.
5 min and the reaction was quenched by adding satd aq NH4Cl. The
whole mixture was extracted with AcOEt. The product was purified
by silica gel column chromatography to afford 2.31 g (99%) of 9 as
a colorless oil. IR (neat) 2929,1721 (CO),1362, 1146,1052, 760 cmꢀ1
;
1H NMR
d 1.3–1.6 (28H, m), 1.46 (9H, s), 2.41 (3H, s), 2.50, 3.09 (each
1H, d, J¼15.6 Hz), 5.27 (1H, m), 7.30, 7.74 (each 2H, d, J¼8.3 Hz). MS
m/z (%) 510 (Mþ, 0.3), 279 (38), 219 (40),140 (100), 57 (54). Calcd for
C29H47ClO3S: M, 510.2939. Found: m/z 510.2934.
3.3. Bicyclo[13.1.0]hexadec-1-ylacetic acid tert-butyl ester (11)
To a flame-dried flask was added dry toluene (4 mL) followed by
i-PrMgCl (0.5 mmol; 2.5 equiv) in ether at ꢀ78 ꢁC. A solution of
adduct 9 (102 mg; 0.2 mmol) in toluene (2.5 mL) was added to the
solution of Grignard reagent dropwise with stirring and the re-
action mixture was slowly allowed to warm to 0 ꢁC for 2 h. The
reaction was quenched with satd aq NH4Cl and the whole mixture
was extracted with CHCl3. The product was purified by silica gel
column chromatography to afford 64.5 mg (96%) of cyclopropane
11 as a colorless oil. IR (neat) 2929, 2857, 1735 (CO), 1459, 1391,
3. Experimental
3.1. General
1366, 1309, 1250, 1147, 1025, 959, 842 cmꢀ1; 1H NMR
d 0.25 (1H, dd,
J¼5.8, 4.8 Hz), 0.47–0.53 (2H, m), 0.59–0.68 (1H, m), 1.08–1.17 (1H,
m), 1.21–1.49 (22H, m), 1.46 (9H, s), 1.54–1.59 (1H, m), 1.76 (1H, d,
J¼15.6 Hz), 1.99–2.15 (1H, m), 2.57 (1H, d, J¼15.6 Hz); 13C NMR
All melting points were measured on a Yanaco MP-S3 heated
stage apparatus and were uncorrected. 1H and 13C NMR spectra
were measured in a CDCl3 solution with JEOL JNM-LA 300, 500,
BRUKER DPX 400 and AV 600 spectrometer. Electron-impact mass
spectra (MS) were obtained at 70 eV by direct insertion by HITACHI
M-80B mass spectrometer. IR spectra were recorded on spectrum
One series Fourier transform infrared spectrometer using either
NaCl plates or KBr pellets. Silica gel 60N (KANTO CHEMICAL) con-
taining 0.5% fluorescence reagent 254 and a quartz column were
used for column chromatography and the products having UV ab-
sorption were detected by UV irradiation. In experiments requiring
dry solvents and reagents, THF and diethyl ether were distilled from
diphenylketyl. Diisopropylamine and toluene were distilled from
CaH2. All reactions involving air- or water-sensitive compounds
were routinely conducted in glassware, which was flame-dried
under a positive pressure of argon. Compounds 13a,6b 13b,6b 13c,6a
13e,7b 14c,7a 14e,7a 18a,7c 18b,7c 18c,6b 19a,7c 19b,7c and 21f7b are
previously reported.
d
79.93 (4), 37.81 (2), 36.71 (2), 29.10 (2), 28.74 (2), 28.17 (1), 27.86
(2), 27.31 (2), 27.17 (2), 26.86 (2), 26.70 (2), 26.49 (2), 26.47 (2),
26.24 (2), 26.22 (2), 26.14 (2), 22.65 (3), 22.11 (4), 18.71 (2). MS m/z
(%) 336 (Mþ, 2), 280 (29), 262 (10), 220 (100), 109 (5), 81 (10), 57
(25). Calcd for C22H40O2: M, 336.3028. Found: m/z 336.3023.
3.4. [Chloro(p-tolylsulfinyl)methylene]cyclooctane (13d)
Colorless crystals; mp 72.5–73.0 ꢁC (hexane–AcOEt); IR (KBr)
2931, 2907, 1579, 1471, 1413, 1086, 1054 (SO), 898, 801 cmꢀ1 1H
;
NMR d 1.37–1.55 (4H, m),1.58–1.63 (2H, m),1.73–1.88 (3H, m), 1.91–
1.99 (1H, m), 2.41 (3H, s), 2.48 (2H, dd, J¼7.0, 4.9 Hz), 2.85 (1H, ddd,
J¼15.0, 7.7, 4.3 Hz), 2.90 (1H, ddd, J¼15.0, 8.9, 4.0 Hz), 7.31 (2H, d,
J¼8.0 Hz), 7.50 (2H, d, J¼8.3 Hz). Anal. Calcd for C16H21ClOS: C,
64.74; H, 7.13; Cl,11.94; S,10.80. Found: C, 64.71; H, 7.09; Cl,11.85; S,
10.85.
3.2. {1-[Chloro(p-tolylsulfinyl)methyl]cyclopentadecyl}acetic
acid tert-butyl ester (9)
3.5. {1-[Chloro(p-tolylsulfinyl)methyl]cyclopentyl}acetic acid
tert-butyl ester (14a)
tert-Butyl acetate (3.1 mL; 22.8 mmol) was added to a solution
of LDA (22.8 mmol) in 40 mL of dry THF at ꢀ78 ꢁC with stirring. The
solution was stirred for 10 min and then a solution of 8 (1.8 g;
4.56 mmol) in THF (5 mL) was added. The solution was stirred for
Colorless oil; IR (neat) 2961, 1723 (CO), 1597, 1455, 1368, 1218,
1151,1056, 812 cmꢀ1; 1H NMR
d 1.47 (9H, s), 1.65–1.74 (4H, m),1.76–
1.85 (2H, m), 2.13–2.20 (2H, m), 2.42 (3H, s), 2.57 (1H, d, J¼15.9 Hz),
3.19 (1H, d, J¼15.9 Hz), 5.31 (1H, s), 7.31 (2H, d, J¼8.6 Hz), 7.71 (2H,

5716
S. Ogata et al. / Tetrahedron 64 (2008) 5711–5720
d, J¼8.0 Hz). MS m/z (%) 370 (Mþ, 0.1), 297 (12), 231 (1), 175 (7), 157
(4), 140 (100), 92 (11), 57 (29). Calcd for C19H27ClO3S: M, 370.1369.
Found: m/z 370.1371.
(23), 81 (32), 57 (59). Calcd for C15H26O2: M, 238.1933. Found: m/z
238.1936.
3.12. Bicyclo[8.1.0]undec-1-ylacetic acid tert-butyl ester (15e)
3.6. {1-[Chloro(p-tolylsulfinyl)methyl]cyclohexyl}acetic acid
tert-butyl ester (14b)
Colorless oil; IR (neat) 2928, 2861, 1732 (CO), 1455, 1392, 1368,
1300, 1255, 1146, 842 cmꢀ1; 1H NMR
d
ꢀ0.20 (0.4H, ddd, J¼6.1, 4.7,
Colorless oil; IR (neat) 2931, 1716 (CO), 1456, 1368, 1255, 1153,
1.3 Hz), 0.22 (0.6H, dd, J¼6.2, 4.6 Hz), 0.41 (0.6H, ddd, J¼8.8, 4.6,
1.5 Hz), 0.50 (0.4H, ddd, J¼10.0, 9.5, 6.3 Hz), 0.57–0.67 (0.6H, m),
0.71 (0.4H, dd, J¼9.2, 4.8 Hz), 0.94–1.02 (0.6H, m), 1.03–1.12 (0.6H,
m), 1.13–1.22 (0.8H, m), 1.23–1.43 (6H, m), 1.45 (3.6H, s), 1.46 (5.4H,
s), 1.47–1.65 (6H, m), 1.67–1.90 (1H, m), 1.75 (0.6H, d, J¼14.3 Hz),
1.76 (0.4H, d, J¼14.4 Hz), 1.95 (0.4H, dt, J¼15.0, 4.7 Hz), 2.25 (0.6H,
dt, J¼14.5, 3.5 Hz), 2.76 (0.4H, d, J¼14.3 Hz), 2.76 (0.6H, d,
J¼14.2 Hz). MS m/z (%) 266 (Mþ, 2), 210 (7), 193 (5), 165 (2), 150
(100), 109 (14), 95 (19), 81 (19), 57 (48). Calcd for C17H30O2: M,
266.2246. Found: m/z 266.2248.
1083, 1055, 811 cmꢀ1 1H NMR
; d 1.23–1.37 (1H, m), 1.40–1.58 (2H,
m), 1.48 (9H, s), 1.58–1.68 (3H, m), 1.72–1.81 (1H, m), 1.86–1.98 (2H,
m), 2.01–2.10 (1H, m), 2.42 (3H, s), 2.71 (1H, d, J¼15.6 Hz), 3.20 (1H,
d, J¼15.5 Hz), 5.29 (1H, s), 7.31 (2H, d, J¼7.8 Hz), 7.74 (2H, d,
J¼7.8 Hz). MS m/z (%) 384 (Mþ, 0.1), 311 (11), 276 (2), 189 (14), 140
(100), 91 (11), 57 (29). Calcd for C20H29ClO3S: M, 384.1526. Found:
m/z 384.1523.
3.7. {1-[Chloro(p-tolylsulfinyl)methyl]cyclooctyl}acetic acid
tert-butyl ester (14d)
3.13. 2-{1-[Chloro(p-tolylsulfinyl)methyl]cyclopentyl}-4-
phenylbutyric acid tert-butyl ester (16a)
Colorless oil; IR (neat) 2927, 1723 (CO), 1471, 1367, 1254, 1153,
1055, 811 cmꢀ1; 1H NMR
d 1.46 (9H, s), 1.47–1.65 (8H, m), 1.71–1.76
(3H, m), 1.90 (1H, ddd, J¼15.2, 9.2, 1.9 Hz), 2.17 (1H, dd, J¼13.2,
8.9 Hz), 2.31 (1H, ddd, J¼15.3, 9.2, 2.7 Hz), 2.42 (3H, s), 2.54 (1H, d,
J¼15.3 Hz), 3.03 (1H, d, J¼15.6 Hz), 5.22 (1H, s), 7.31 (2H, d,
J¼8.2 Hz), 7.73 (2H, d, J¼8.2 Hz). MS m/z (%) 412 (Mþ, trace), 356 (1),
339 (10), 297 (1), 217 (12), 181 (20), 140 (100), 121 (35), 92 (8), 57
(25). Calcd for C22H33ClO3S: M, 412.1838. Found: m/z 412.1826.
Colorless crystals; mp 125.0–126.0 ꢁC (hexane–AcOEt); IR (KBr)
2963, 1712 (CO), 1595, 1455, 1365, 1145, 1053, 814, 696 cmꢀ1 1H
;
NMR
d 1.51 (9H, s), 1.55–1.65 (2H, m), 1.68–1.80 (2H, m), 1.86 (1H,
dddd, J¼13.0, 10.4, 6.5, 2.6 Hz), 1.92–2.20 (5H, m), 2.42 (3H, s), 2.56
(1H, ddd, J¼13.7, 10.0, 6.6 Hz), 2.68 (1H, ddd, J¼14.1, 10.6, 5.0 Hz),
3.21 (1H, dd, J¼11.8, 2.7 Hz), 4.61 (1H, m), 7.15–7.24 (3H, m), 7.28–
7.33 (2H, m), 7.29 (2H, d, J¼7.8 Hz), 7.62 (2H, d, J¼8.3 Hz). Anal.
Calcd for C27H35ClO3S: C, 68.26; H, 7.43; Cl, 7.46; S, 6.75. Found: C,
68.15; H, 7.24; Cl, 7.43; S, 6.73.
3.8. Bicyclo[3.1.0]hex-1-ylacetic acid tert-butyl ester (15a)
Colorless oil; IR (neat) 2932, 2862, 1732 (CO), 1455, 1392, 1368,
1256, 1141 cmꢀ1; 1H NMR
d
0.35 (1H, dd, J¼8.2, 5.3 Hz), 0.43 (1H, t,
3.14. 2-{1-[Chloro(p-tolylsulfinyl)methyl]cyclohexyl}-
propionic acid tert-butyl ester (16b)
J¼4.3 Hz), 1.06–1.13 (1H, m), 1.13–1.23 (1H, m), 1.45 (9H, m), 1.57–
1.69 (2H, m), 1.71–1.83 (2H, m), 2.30 (1H, d, J¼14.6 Hz), 2.37 (1H, d,
J¼14.7 Hz). MS m/z (%) 183 ([MꢀH]þ, 41), 179 (74), 167 (28), 124
(100), 96 (43), 81 (60), 57 (82).
Colorless oil; IR (neat) 2930, 1728 (CO), 1456, 1367, 1145, 1056,
811, 760 cmꢀ1
;
1H NMR
d
1.22–1.34 (4H, m), 1.34 (3H, d, J¼7.0 Hz),
1.47 (9H, m), 1.60–1.79 (3H, m), 1.84 (1H, ddd, J¼13.8, 11.7, 4.6 Hz),
2.08–2.17 (1H, m), 2.43 (3H, s), 2.45–2.52 (1H, m), 3.11 (1H, q,
J¼7.1 Hz), 4.95 (1H, m), 7.32 (2H, d, J¼8.2 Hz), 7.72 (2H, d, J¼8.2 Hz).
MS (FAB) m/z (%) 399 ([MþH]þ, 42), 343 (100), 325 (21), 269 (3),
203 (15), 167 (73), 140 (16), 123 (16), 93 (11), 57 (14). Calcd for
3.9. Bicyclo[4.1.0]hept-1-ylacetic acid tert-butyl ester (15b)
Colorless oil; IR (neat) 2931, 2859, 1732 (CO), 1455, 1368, 1256,
1146 cmꢀ1
;
1H NMR
d
0.26 (1H, t, J¼4.8 Hz), 0.47 (1H, dd, J¼9.0,
4.6 Hz), 0.81–0.91 (1H, m), 1.10–1.36 (4H, m), 1.46 (9H, s), 1.53–1.62
(1H, m), 1.73 (2H, t, J¼6.4 Hz), 1.91 (1H, sextet, J¼6.8 Hz), 2.01 (1H,
d, J¼14.5 Hz), 2.16 (1H, d, J¼14.6 Hz). MS m/z (%) 210 (Mþ, 0.2), 154
(52), 109 (100), 79 (13), 57 (62). Calcd for C13H22O2: M, 210.1620.
Found: m/z 210.1621.
C
21H32ClO3S: [MþH], 399.1761. Found: m/z 399.1759.
3.15. 2-{1-[Chloro(p-tolylsulfinyl)methyl]cyclohexyl}hexanoic
acid tert-butyl ester (16c)
Colorless oil; IR (neat) 2929, 1723 (CO), 1456, 1367, 1144, 1057,
3.10. Cyclopropane (15c)
812 cmꢀ1
;
1H NMR
d
0.93 (3H, t, J¼7.1 Hz), 1.20–1.47 (8H, m), 1.49
(9H, s), 1.60–1.76 (3H, m), 1.78–1.93 (3H, m), 2.06–2.14 (1H, m), 2.44
(3H, m), 2.49–2.58 (1H, m), 2.94 (1H, dd, J¼10.2, 4.3 Hz), 4.98 (1H,
s), 7.33 (2H, d, J¼8.0 Hz), 7.73 (2H, d, J¼8.2 Hz). MS (FAB) m/z (%)
441 ([MþH]þ, 50), 385 (100), 367 (36), 245 (27), 209 (80), 140 (21),
93 (14), 57 (20). Calcd for C24H38ClO3S: [MþH], 441.2230. Found:
m/z 441.2228.
Colorless oil; IR (neat) 2935, 1728 (CO), 1393, 1368, 1259, 1149,
1075, 948, 841 cmꢀ1
;
1H NMR
d
0.47 (1H, t, J¼5.2 Hz), 0.61 (1H,
dd, J¼9.2, 4.9 Hz), 0.41–0.46 (1H, m), 1.35 (1H, ddd, J¼14.6, 9.8,
4.9 Hz), 1.46 (9H, s), 1.54 (1H, ddt, J¼13.4, 5.8, 1.8 Hz), 1.74 (1H, d,
J¼14.4 Hz), 1.99 (1H, d, J¼13.1 Hz), 1.94–2.01 (2H, m), 2.06 (1H, d,
J¼14.4 Hz), 2.20 (1H, d, J¼14.4 Hz), 3.85–3.92 (4H, m). MS m/z (%)
268 (Mþ, 6), 212 (9), 195 (8), 183 (2), 167 (12), 153 (4), 99 (13), 86
(100), 57 (6). Calcd for C15H24O4: M, 268.1675. Found: m/z 268.1671.
3.16. 2-{1-[Chloro(p-tolylsulfinyl)methyl]cyclohexyl}-
4-phenylbutyric acid tert-butyl ester (16d)
3.11. Bicyclo[6.1.0]non-1-ylacetic acid tert-butyl ester (15d)
Colorless oil; IR (neat) 2929, 1716 (CO), 1456, 1368, 1253, 1144,
Colorless oil; IR (neat) 2925, 2856, 1732 (CO), 1456, 1368, 1314,
1055, 757 cmꢀ1; 1H NMR
d 1.15–1.36 (2H, m), 1.36–1.51 (2H, m), 1.54
1257, 1144, 1035, 966, 846 cmꢀ1
;
1H NMR
d
ꢀ0.02 (1H, dt, J¼5.0,
(9H, s), 1.60–176 (3H, m), 1.77–1.91 (1H, m), 2.05–2.20 (2H, m), 2.22
(1H, dd, J¼8.2, 6.9 Hz), 2.43 (3H, s), 2.46–2.56 (1H, m), 2.56 (1H, dd,
J¼16.4, 8.2 Hz), 2.63–2.79 (1H, m), 3.02 (1H, dd, J¼8.4, 6.8 Hz), 4.93
(1H, s), 7.17–7.35 (7H, m), 7.67 (2H, d, J¼8.2 Hz). MS (FAB) m/z (%)
489 ([MþH]þ, 22), 433 (100), 415 (47), 379 (17), 293 (43), 257 (34),
1.2 Hz), 0.39–0.47 (1H, m), 0.69 (1H, dd, J¼8.5, 4.6 Hz), 0.91–1.07
(2H, m), 1.26–1.47 (4H, m), 1.50–1.71 (5H, m), 1.45 (9H, s), 2.02 (2H,
ddt, J¼14.7, 10.7, 3.6 Hz), 2.76 (1H, dd, J¼14.1, 1.3 Hz). MS m/z (%)
238 (Mþ, 2), 223 (5), 182 (22), 165 (7), 154 (11), 137 (9), 122 (100), 95

S. Ogata et al. / Tetrahedron 64 (2008) 5711–5720
5717
211 (35), 91 (73), 57 (50). Calcd for C28H38ClO3S: [MþH], 489.2230.
Found: m/z 489.2230.
J¼3.6 Hz), 0.62–0.72 (2H, m), 1.07–1.28 (4H, m), 1.46 (9H, s), 1.47–
1.55 (2H, m), 1.58–1.66 (1H, m), 1.72 (1H, dddd, J¼13.4, 10.3, 6.7,
5.0 Hz), 1.79–1.92 (2H, m), 2.11 (1H, ddt, J¼13.5, 10.0, 5.2 Hz), 2.54
(1H, ddd, J¼13.7, 10.0, 6.5 Hz), 2.63 (1H, ddd, J¼13.6, 10.2, 5.3 Hz),
7.18 (3H, d, J¼6.8 Hz), 7.27 (2H, dd, J¼8.4, 7.3 Hz). MS m/z (%) 314
(Mþ, 6), 258 (41), 240 (7), 213 (6), 167 (8), 154 (57), 131 (13), 104
(100), 95 (67), 91 (51), 57 (42). Calcd for C21H30O2: M, 314.2246.
Found: m/z 314.2246.
3.17. 2-{1-[Chloro(p-tolylsulfinyl)methyl]cyclooctyl}propionic
acid tert-butyl ester (16e)
Colorless oil; IR (neat) 2926, 1728 (CO), 1597, 1456, 1368, 1255,
1152, 1057, 811 cmꢀ1
;
1H NMR
d
1.35 (3H, d, J¼7.3 Hz), 1.40–1.88
(10H, m), 1.47 (9H, m), 2.01 (2H, t, J¼5.3 Hz), 2.07 (1H, ddd, J¼15.2,
7.7, 2.2 Hz), 2.29 (1H, ddd, J¼15.2, 9.3, 2.3 Hz), 2.43 (3H, s), 3.00 (1H,
q, J¼7.2 Hz), 4.61 (1H, s), 7.32 (2H, d, J¼8.1 Hz), 7.71 (2H, d,
J¼8.4 Hz). MS (FAB) m/z (%) 427 ([MþH]þ, 60), 371 (100), 353 (17),
231 (17), 195 (68), 154 (22), 121 (43), 93 (14), 57 (20). Calcd for
3.23. 2-Bicyclo[6.1.0]non-1-ylpropionic acid tert-butyl ester
(17e)
Colorless oil; IR (neat) 2927, 1729 (CO), 1456, 1367, 1252, 1151,
C
23H36ClO3S: [MþH], 427.2074. Found: m/z 427.2073.
851 cmꢀ1; 1H NMR
d
ꢀ0.25 (1H, t, J¼4.7 Hz), 0.55–0.64 (1H, m), 0.66
(1H, dd, J¼4.1, 8.9 Hz), 0.95–1.12 (2H, m), 1.08 (3H, d, J¼6.8 Hz),
1.29–1.41 (4H, m), 1.43 (9H, s), 1.49–1.62 (2H, m), 1.63–1.80 (2H, m),
1.92–2.04 (2H, m), 2.45 (1H, q, J¼6.7 Hz). MS m/z (%) 252 (Mþ, 3),
237 (5), 196 (27), 151 (12), 123 (100), 109 (11), 81 (41), 67 (25), 57
(77). Calcd for C16H28O2: M, 252.2090. Found: m/z 252.2097.
3.18. 2-{1-[Chloro(p-tolylsulfinyl)methyl]cyclooctyl}hexanoic
acid tert-butyl ester (16f)
Colorless oil; IR (neat) 2928, 1723 (CO), 1455, 1367, 1254, 1150,
1057, 811 cmꢀ1; 1H NMR
d
0.85–0.93 (2H, m), 0.92 (3H, t, J¼7.0 Hz),
1.19–1.72 (10H, m), 1.49 (9H, s), 1.73–1.81 (2H, m), 1.85 (2H, dd,
J¼14.5, 7.7 Hz),1.92–2.07 (3H, m), 2.33 (1H, ddd, J¼15.4, 8.6, 3.1 Hz),
2.43 (3H, s), 2.86 (1H, dd, J¼8.5, 7.4 Hz), 4.58 (1H, m), 7.32 (2H, d,
J¼8.2 Hz), 7.71 (2H, d, J¼8.2 Hz). MS (FAB) m/z (%) 469 ([MþH]þ,
60), 413 (100), 395 (33), 273 (28), 237 (70), 191 (16), 154 (18), 121
(59), 93 (11), 57 (28). Calcd for C26H42ClO3S: [MþH], 469.2543.
Found: m/z 469.2541.
3.24. 2-Bicyclo[6.1.0]non-1-ylhexanoic acid tert-butyl ester
(17f)
Colorless oil; IR (neat) 2926, 2859, 1728 (CO), 1469, 1367, 1256,
1150, 1035, 852 cmꢀ1; 1H NMR
d
ꢀ0.26 (1H, t, J¼4.9 Hz), 0.46–0.56
(1H, m), 0.71 (1H, dd, J¼9.0, 4.3 Hz), 0.93–1.06 (2H, m), 1.14–1.78
(17H, m), 1.44 (9H, s), 1.92–2.02 (2H, m), 2.61 (1H, dd, J¼11.2,
2.6 Hz). MS m/z (%) 294 (Mþ, 4), 238 (28), 210 (3), 193 (11), 181 (28),
123 (100), 116 (42), 81 (35), 57 (54). Calcd for C19H34O2: M,
294.2559. Found: m/z 294.2567.
3.19. 2-Bicyclo[3.1.0]hex-1-yl-4-phenylbutyric acid tert-butyl
ester (17a)
Colorless oil; IR (neat) 2933, 2862, 1728 (CO), 1605, 1497, 1455,
3.25. (Z)-1-[Chloro(p-tolylsulfinyl)methylene]-1,2,3,4-
tetrahydro-naphthalene (18d)
1392, 1367, 1256, 1143, 1020, 851, 699 cmꢀ1
;
1H NMR
d
0.28 (0.2H,
dd, J¼8.1, 5.1 Hz), 0.37 (0.8H, t, J¼4.7 Hz), 0.41–0.49 (1H, m), 1.04
(0.8H, dt, J¼8.0, 4.0 Hz), 1.09–1.25 (1.2H, m), 1.46 (1.8H, s), 1.47
(7.2H, s), 1.61–1.79 (6H, m), 1.98–2.13 (2H, m), 2.48–2.68 (2H, m),
7.18 (3H, d, J¼6.8 Hz), 7.27 (2H, t, J¼8.3 Hz). MS m/z (%) 300 (Mþ, 3),
280 (2), 244 (50), 199 (12), 140 (54), 117 (30), 104 (100), 91 (50).
Calcd for C20H28O2: M, 300.2089. Found: m/z 300.2087.
Colorless crystals; mp 142–143 ꢁC (hexane–AcOEt); IR (KBr)
2968, 1584, 1451, 1435, 1289, 1175, 1086, 1060, 908, 812, 521 cmꢀ1
;
1H NMR
d 1.88–2.05 (1H, m), 2.07–2.22 (1H, m), 2.41 (3H, m), 2.89
(2H, t, J¼6.5 Hz), 3.06 (1H, ddd, J¼14.3, 7.5, 5.4 Hz), 3.27 (1H, ddd,
J¼14.3, 8.2, 5.2 Hz), 7.13–7.22 (2H, m), 7.27 (1H, dd, J¼6.9, 1.7 Hz),
7.33 (2H, d, J¼7.9 Hz), 7.55 (2H, d, J¼8.3 Hz), 7.85–7.91 (1H, m). Anal.
Calcd for C18H17ClOS: C, 68.23; H, 5.41; Cl, 11.19; S, 10.12. Found: C,
68.23; H, 5.42; Cl, 11.09; S, 10.03.
3.20. 2-Bicyclo[4.1.0]hept-1-ylpropionicacid tert-butyl
ester (17b)
Colorless oil; IR (neat) 2979, 2931, 1729 (CO), 1592, 1457, 1368,
3.26. (Z)-1-[Chloro(p-tolylsulfinyl)methylene]indane (18e)
1246, 1153, 1118, 852 cmꢀ1; 1H NMR
d 0.24–0.30 (1H, m), 0.66–0.75
(1H, m), 1.04–1.11 (1H, m), 1.08 (3H, d, J¼7.2 Hz), 1.12–1.29 (5H, m),
1.44 (9H, s), 1.59–1.69 (2H, m), 1.76–1.89 (2H, m). MS m/z (%) 224
(Mþ, 0.1), 209 (0.3), 181 (0.7), 168 (22), 154 (3), 123(26), 95 (100), 81
(28), 57 (52).
Colorless crystals; mp 140–141 ꢁC (hexane–AcOEt); IR (KBr)
2919, 1589, 1492, 1442, 1305, 1085, 1057 (SO), 879, 807, 759,
527 cmꢀ1; 1H NMR
d 2.41 (3H, s), 3.07–3.23 (2H, m), 3.24 (1H, ddd,
J¼16.4, 8.7, 5.2 Hz), 3.56 (1H, ddd, J¼16.6, 8.2, 3.9 Hz), 7.24–7.35
(1H, m), 7.32 (2H, d, J¼8.3 Hz), 7.35–7.42 (2H, m), 7.56 (2H, d,
J¼8.2 Hz), 8.27 (1H, d, J¼7.96 Hz). Anal. Calcd for C17H15ClOS: C,
67.43; H, 4.99; Cl, 11.71; S, 10.59. Found: C, 67.33; H, 4.99; Cl, 11.60;
S, 10.60.
3.21. 2-Bicyclo[4.1.0]hept-1-ylhexanoic acid tert-butyl
ester (17c)
Colorless oil; IR (neat) 2930, 2860, 1727 (CO), 1455, 1367, 1256,
1151 cmꢀ1
;
1H NMR
d
0.22 (1H, t, J¼4.8 Hz), 0.65 (1H, dd, J¼9.3,
3.27. {1-[Chloro(p-tolylsulfinyl)methyl]-1,2,3,4-tetrahydro-
naphthalen-1-yl}acetic acid tert-butyl ester (19c)
4.5 Hz), 0.68–0.76 (1H, m), 0.89 (3H, t, J¼7.0 Hz),1.08–1.35 (10H, m),
1.37–1.51 (1H, m), 1.44 (9H, m), 1.63 (1H, dd, J¼13.2, 6.8 Hz), 1.68–
1.79 (1H, m), 1.79–1.90 (2H, m). MS m/z (%) 266 (Mþ, 2), 210 (20),
154 (22), 116 (16), 109 (11), 95 (100), 57 (27). Calcd for C17H30O2: M,
266.2246. Found: m/z 266.2248.
Derived from 18c; colorless crystals; mp 89–91 ꢁC (hexane–
AcOEt); IR (KBr) 2952, 1720 (CO), 1494, 1448, 1367, 1213, 1143, 1056,
811 cmꢀ1 1H NMR
; d 1.34 (9H, s), 1.72–1.89 (1H, m), 1.99 (1H, dt,
J¼13.7, 5.3 Hz), 2.32 (2H, t, J¼6.5 Hz), 2.41 (3H, s), 2.74–2.84 (2H, m),
2.91 (1H, d, J¼15.6 Hz), 3.15 (1H, J¼15.7 Hz), 5.49 (1H, s), 7.11 (1H,
dd, J¼7.0, 1.8 Hz), 7.20 (2H, ddt, J¼14.0, 7.0, 1.6 Hz), 7.29 (2H, d,
J¼8.2 Hz), 7.59 (1H, dd, J¼7.1, 2.0 Hz), 7.63 (2H, d, J¼8.2 Hz). Anal.
Calcd for C24H29ClO3S: C, 66.57; H, 6.75; Cl, 8.19; S, 7.40. Found: C,
66.81; H, 6.78; Cl, 8.06; S, 7.37.
3.22. 2-Bicyclo[4.1.0]hept-1-yl-4-phenylbutyric acid tert-
butyl ester (17d)
Colorless oil; IR (neat) 2930, 2859, 1781 (CO), 1604, 1496, 1454,
1367, 1256, 1226, 1144, 1021, 850, 699 cmꢀ1 1H NMR
; d 0.24 (1H, t,

5718
S. Ogata et al. / Tetrahedron 64 (2008) 5711–5720
3.28. {1-[Chloro(p-tolylsulfinyl)methyl]-1,2,3,4-tetra-
hydronaphthalen-1-yl}acetic acid tert-butyl ester (19d)
(76), 115 (23), 57 (100). Calcd for C16H20O2: M, 244.1462. Found: m/z
244.1463.
Derived from 18d; colorless crystals; mp 130–133 ꢁC (hexane–
3.34. [Chloro(p-tolylsulfinyl)methylene]cycloheptane (13f)
AcOEt); IR (KBr) 2938, 1710 (CO), 1494, 1447, 1367, 1225, 1153, 1083,
1054, 815, 741 cmꢀ1; 1H NMR
d
1.34 (9H, s), 1.77–2.08 (2H, m), 2.42
Colorless crystals; mp 95–95.5 ꢁC (hexane–AcOEt); IR (KBr)
(3H, s), 2.48 (1H, ddt, J¼13.7, 3.8, 0.9 Hz), 2.58 (1H, ddd, J¼13.7, 12.2,
3.8 Hz), 2.70–2.93 (2H, m), 3.04 (1H, d, J¼15.5 Hz), 3.30 (1H, d,
J¼15.6 Hz), 5.71 (1H, s), 7.05–7.18 (3H, m), 7.32 (2H, d, J¼8.0 Hz),
7.41–7.47 (1H, m), 7.79 (2H, d, J¼8.2 Hz). Anal. Calcd for
2930, 2854, 1441, 1084 (SO), 1055 (SO), 803, 527 cmꢀ1 1H NMR
;
d
1.44–1.74 (7H, m), 1.83–1.95 (1H, m), 2.41 (3H, s), 2.53 (2H, m),
2.86–3.06 (2H, m), 7.31 (2H, d, J¼8.1 Hz), 7.49 (2H, d, J¼8.1 Hz).
Anal. Calcd for C15H19ClOS: C, 63.70; H, 6.77; Cl, 12.53; S, 11.34.
Found: C, 63.86; H, 6.71; Cl, 12.54; S, 11.35.
C
24H29ClO3S: C, 66.57; H, 6.75; Cl, 8.19; S, 7.40. Found: C, 66.14; H,
6.74; Cl, 8.07; S, 7.33.
3.35. [Chloro(p-tolylsulfinyl)methylene]cyclododecane (13g)
3.29. {1-[Chloro(p-tolylsulfinyl)methyl]indan-1-yl}acetic acid
tert-butyl ester (19e)
Colorless crystals; mp 104–104.5 ꢁC (hexane–AcOEt); IR (KBr)
2931, 2849, 1470, 1086 (SO), 1052 (SO), 893, 807, 522 cmꢀ1; 1H NMR
Colorless crystals; mp 115–116.5 ꢁC (hexane–AcOEt); IR (KBr)
d
1.38–1.78 (18H, m), 2.30–2.46 (2H, m), 2.41 (3H, s), 2.65–2.85 (2H,
m), 7.31 (2H, d, J¼8.1 Hz), 7.48 (2H, d, J¼8.1 Hz). Anal. Calcd for
20H29ClOS: C, 68.06; H, 8.28; Cl, 10.04; S, 9.08. Found: C, 68.06; H,
2980, 1718 (CO), 1456, 1367, 1226, 1148, 1057, 814, 506 cmꢀ1 1H
;
NMR
d
1.33 (9H, s), 2.42 (3H, s), 2.43 (1H, ddd, J¼13.1, 8.7, 4.1 Hz),
C
2.82 (1H, ddd, J¼13.3, 9.7, 7.4 Hz), 2.94 (1H, d, J¼15.7 Hz), 3.03 (1H,
dd, J¼16.1, 8.1 Hz), 3.15 (1H, ddd, J¼16.1, 9.8, 4.2 Hz), 3.26 (1H, d,
J¼15.8 Hz), 5.72 (1H, m), 7.10–7.20 (1H, m), 7.21–7.25 (2H, m), 7.26–
7.29 (1H, m), 7.31 (2H, d, J¼8.2 Hz), 7.68 (2H, d, J¼8.2 Hz). Anal.
Calcd for C23H27ClO3S: C, 65.93; H, 6.50; Cl, 8.46; S, 7.65. Found: C,
65.98; H, 6.48; Cl, 8.40; S, 7.70.
8.21; Cl, 9.95; S, 9.06.
3.36. 2-{1-[Chloro(p-tolylsulfinyl)methyl]cyclopentyl}-
N,N-dimethylacetamide (21a)
N,N-Dimethylacetamide (0.46 mL; 5.0 mmol) was added to
a solution of LDA (5.0 mmol) in 15 mL of dry THF at ꢀ78 ꢁC with
stirring. The solution was stirred for 10 min and then a solution of
13a (254 mg; 1.0 mmol) in THF (5 mL) was added. The reaction
mixture was slowly allowed to warm to ꢀ50 ꢁC for 40 min. The
reaction was quenched with satd aq NH4Cl and the whole mixture
was extracted with CHCl3. The product was purified by silica gel
column chromatography to afford 200 mg (57%) of 21a as a color-
less oil (12:1 mixture of two diastereomers). IR (neat) 2954, 1645
3.30. Bicyclo[4.1.0]hept-2-en-1-ylacetic acid tert-butyl
ester (20a)
Colorless oil; IR (neat) 2979, 2930, 1732 (CO), 1455, 1368, 1256,
1147, 1089, 964, 762 cmꢀ1
;
1H NMR
d
0.65 (1H, dd, J¼8.3, 4.6 Hz),
0.79 (1H, t, J¼5.2 Hz), 1.26–1.29 (1H, m), 1.44 (9H, s), 1.55–1.64 (1H,
m), 1.66–1.74 (1H, m), 1.90–2.00 (2H, m), 2.08 (1H, d, J¼14.9 Hz),
2.38 (1H, d, J¼14.9 Hz), 5.45 (1H, ddd, J¼9.5, 6.8, 1.9 Hz), 5.94 (1H,
dd, J¼10.1, 2.8 Hz). MS m/z (%) 208 (Mþ, 7), 193 (11), 152 (100), 132
(12), 107 (64), 93 (65), 57 (88), 18 (77). Calcd for C13H20O2: M,
208.1463. Found: m/z 208.1470.
(CO),1398, 1085 (SO), 1052 (SO), 812 cmꢀ1; 1H NMR
d 1.61–1.74 (4H,
m), 1.76–1.86 (2H, m), 2.22–2.30 (2H, m), 2.41 (3H, s), 2.60 (0.9H, d,
J¼16.6 Hz), 2.82 (0.2H, s), 2.95 (3H, s), 3.02 (2.8H, s), 3.05 (0.2H, s),
3.40 (0.9H, d, J¼16.6 Hz), 5.67 (0.1H, s), 5.79 (0.9H, s), 7.29 (1.8H, d,
J¼7.9 Hz), 7.31 (0.2H, d, J¼8.2 Hz), 7.51 (0.2H, d, J¼8.2 Hz), 7.68
(1.8H, d, J¼7.9 Hz). MS m/z (%) 341 (Mþ, 0.5), 204 (18), 202 (54), 166
(62), 139 (48), 121 (28), 91 (32), 72 (100). Calcd for C17H24ClNO2S:
M, 341.1216. Found: m/z 341.1216.
3.31. (1,1a,2,3-Tetrahydrocyclopropa[a]naphthalen-7b-yl)-
acetic acid tert-butyl ester (20c)
Colorless oil; IR (neat) 2978, 2929, 1732 (CO), 1495, 1455, 1368,
1280, 1251, 1151, 738 cmꢀ1
;
1H NMR
d
0.82 (1H, dd, J¼8.4, 5.3 Hz),
3.37. 2-{1-[Chloro(p-tolylsulfinyl)methyl]cyclohexyl}-
N,N-dimethylacetamide (21b)
0.98 (1H, t, J¼5.5 Hz), 1.32 (9H, s), 1.49–1.56 (1H, m), 1.88 (1H, ddt,
J¼12.9, 5.2, 3.4 Hz), 2.06 (1H, ddd, J¼13.0, 5.8, 2.6 Hz), 2.18 (1H, d,
J¼16.1 Hz), 2.48 (1H, ddd, J¼16.1, 12.6, 6.1 Hz), 2.65 (1H, ddd, J¼16.1,
5.3, 2.7 Hz), 3.14 (1H, d, J¼16.1 Hz), 7.03 (1H, dd, J¼6.7,1.2 Hz), 7.06–
7.17 (2H, m), 7.36 (1H, d, J¼7.6 Hz). MS m/z (%) 258 (Mþ, 7), 238 (3),
202 (100), 185 (10), 157 (29), 142 (67), 129 (26), 115 (21), 57 (37).
Calcd for C17H22O2: M, 258.1619. Found: m/z 258.1620.
Main product: colorless oil; IR (neat) 2929, 1634 (CO), 1456,
1398, 1147, 1051 (SO), 812 cmꢀ1; 1H NMR
d 1.22–1.75 (5H, m), 1.87–
1.96 (1H, m), 1.99–2.19 (4H, m), 2.41 (3H, s), 2.80 (1H, d, J¼16.6 Hz),
2.99 (3H, br s), 3.06 (3H, br s), 3.25 (1H, d, J¼16.6 Hz), 5.80 (1H, s),
7.29 (2H, d, J¼8.1 Hz), 7.70 (2H, d, J¼8.1 Hz). MS m/z (%) 355 (Mþ,
0.3), 246 (25), 218 (22), 216 (65), 180 (32), 153 (100), 139 (25), 87
(45), 72 (84). Calcd for C18H26ClNO2S: M, 355.1373. Found: m/z
355.1372.
3.32. (1-Isobutyl-1,2,3,4-tetrahydronaphthalen-1-yl)acetic
acid tert-butyl ester (20d)
Minor product: colorless oil; IR (neat) 2931, 1634 (CO), 1398,
Colorless oil; IR (neat) 2932, 1723 (CO), 1455, 1392, 1368, 1255,
1089 (SO), 1061 (SO), 811 cmꢀ1; 1H NMR
d 1.25–1.50 (4H, m), 1.61–
1147, 750 cmꢀ1; 1H NMR
d
0.88 (6H, d, J¼6.7 Hz), 1.43 (9H, s), 1.64–
1.67 (2H, m), 1.82–2.11 (4H, m), 2.40 (3H, s), 2.88 (1H, d, J¼16.8 Hz),
2.90 (1H, d, J¼16.8 Hz), 2.96 (3H, s), 3.10 (3H, s), 5.50 (1H, s), 7.31
(2H, d, J¼8.2 Hz), 7.51 (2H, d, J¼8.2 Hz). MS m/z (%) 355 (Mþ, 0.1),
218 (33), 216 (100), 180 (31), 139 (7), 72 (76). Calcd for
1.75 (2H, m), 1.82–1.87 (2H, m), 1.90–2.04 (2H, m), 2.71–2.80 (2H,
m), 2.82–2.88 (2H, m), 7.05–7.12 (4H, m).
3.33. (3,4-Dihydronaphthalen-1-yl)acetic acid tert-butyl
C18H26ClNO2S: M, 355.1373. Found: m/z 355.1375.
ester (20e)
3.38. 2-{1-[Chloro-(p-tolylsulfinyl)-methyl]-cyclopentyl}-
N,N-dimethylacetamide (21c)
Colorless oil; IR (neat) 2978, 2932, 1732 (CO), 1487, 1456, 1368,
1257, 1143, 754 cmꢀ1; 1H NMR
d
1.46 (9H, s), 2.34 (2H, t, J¼8.3 Hz),
2.84 (2H, t, J¼8.3 Hz), 3.11 (2H, s), 6.32 (1H, s), 6.99 (1H, d, J¼6.7 Hz),
Main product: colorless oil; IR (neat) 2923, 2858, 1645 (CO),
7.06–7.16 (3H, m). MS m/z (%) 244 (Mþ, 20), 188 (79), 143 (93), 128
1398, 1085 (SO), 1052 (SO), 811, 734 cmꢀ1; 1H NMR
d 1.36–1.42 (1H,

S. Ogata et al. / Tetrahedron 64 (2008) 5711–5720
5719
m), 1.49–1.59 (3H, m), 1.63–1.84 (5H, m), 2.06–2.12 (1H, m), 2.19–
3.43. 2-Bicyclo[5.1.0]oct-1-yl-N,N-dimethylacetamide (22c)
2.30 (2H, m), 2.41 (3H, s), 2.67 (1H, d, J¼16.5 Hz), 2.97 (3H, br s),
3.04 (3H, br s), 3.25 (1H, d, J¼16.5 Hz), 5.86 (1H, s), 7.29 (2H, d,
J¼8.2 Hz), 7.70 (2H, d, J¼8.2 Hz). MS m/z (%) 369 (Mþ, 1.4), 278 (28),
240 (80), 232 (28), 230 (88), 139 (56), 123 (62), 87 (93), 72 (100).
Calcd for C19H28ClNO2S: M, 369.1530. Found: m/z 369.1526.
Colorless oil; IR (neat) 2918, 1651 (CO), 1465, 1393, 1267, 1141,
1026 cmꢀ1; 1H NMR
(1H, dt, J¼13.6, 10.4 Hz), 1.11–1.85 (7H, m), 1.96 (1H, d, J¼14.8 Hz),
2.08–2.21 (2H, m), 2.79 (1H, d, J¼14.8 Hz), 2.93 (3H, s), 3.01 (3H, s).
MS m/z (%) 195 (Mþ, 20), 180 (19), 138 (21), 87 (81), 72 (100), 45
(23). Calcd for C12H21NO: M, 195.1622. Found: m/z 195.1623.
d
0.39 (1H, t, J¼4.3 Hz), 0.64–0.79 (2H, m), 0.98
3.39. 2-{1-[Chloro(p-tolylsulfinyl)methyl]cyclooctyl}-
N,N-dimethylacetamide (21d)
3.44. 2-Bicyclo[6.1.0]non-1-yl-N,N-dimethylacetamide (22d)
Main product: colorless oil; IR (neat) 2922, 1646 (CO), 1398,
1266, 1053 (SO), 812 cmꢀ1; 1H NMR
d 1.39–1.81 (10H, m), 1.84–2.02
Colorless oil; IR (neat) 2921, 1651 (CO), 1393, 1138, 1032 cmꢀ1
1H NMR
;
(2H, m), 2.18–2.25 (1H, m), 2.32–2.43 (1H, m), 2.41 (3H, s), 2.56 (1H,
d, J¼16.4 Hz), 2.95 (3H, s), 3.05 (3H, s), 3.15 (1H, J¼16.4 Hz), 5.77
(1H, s), 7.29 (2H, d, J¼8.0 Hz), 7.71 (2H, d, J¼8.0 Hz). MS m/z (%) 383
(Mþ, 0.25), 244 (32), 208 (30), 181 (100), 121 (30), 91 (23), 87 (43),
72 (52). Calcd for C20H30ClNO2S: M, 383.1686. Found: m/z 383.1679.
d
0.05 (1H, t, J¼5.1 Hz), 0.42–0.52 (1H, m), 0.60 (1H, dd,
J¼8.7, 4.6 Hz), 0.90–1.15 (2H, m), 1.31–1.62 (8H, m), 1.84 (1H, d,
J¼15.2 Hz), 2.01 (1H, dq, J¼14.3, 3.3 Hz), 2.15 (1H, dt, J¼14.9,
3.8 Hz), 2.89 (1H, d, J¼15.2 Hz), 2.93 (3H, s), 2.99 (3H, s). MS m/z (%)
209 (Mþ, 15), 166 (10), 138 (15), 87 (93), 72 (100), 45 (28). Calcd for
C
13H23NO: M, 209.1777. Found: m/z 209.1770.
3.40. 2-{1-[Chloro(p-tolylsulfinyl)methyl]cyclododecyl}-
N,N-dimethylacetamide (21e)
3.45. 2-Bicyclo[10.1.0]tridec-1-yl-N,N-dimethylacetamide
(22e)
Main product: colorless, amorphous; IR (KBr) 2929, 2861, 1644
(CO), 1471, 1398, 1084 (SO), 1049 (SO), 810, 732 cmꢀ1 1H NMR
;
Colorless oil (3:1 mixture of two diastereomers); IR (neat) 2927,
1652 (CO), 1447, 1393, 1264, 1137 cmꢀ1 1H NMR
; d 0.05 (0.25H, t,
d
1.25–1.50 (16H, m), 1.56–1.73 (3H, m), 1.80–1.90 (2H, m), 2.02–
2.07 (1H, m), 2.38 (1H, d, J¼17.6 Hz), 2.41 (3H, s), 2.96 (3H, br s),
3.03 (3H, s), 3.30 (1H, d, J¼17.6 Hz), 5.95 (1H, s), 7.29 (2H, d,
J¼8.2 Hz), 7.69 (2H, d, J¼8.2 Hz). MS m/z (%) 439 (Mþ, 0.1), 281 (13),
252 (52), 87 (100), 72 (40). Calcd for C24H38ClNO2S: M, 439.2312.
Found: m/z 439.2306.
J¼5.1 Hz), 0.18 (0.75H, dd, J¼5.9, 4.9 Hz), 0.50–0.60 (1H, m), 0.62–
0.70 (1H, m), 0.75–0.90 (1H, m), 1.02–1.68 (17.25H, m), 1.83–1.87
(1H, m), 1.91 (0.75H, d, J¼15.8 Hz), 1.96 (0.25H, d, J¼15.2 Hz), 2.22–
2.28 (0.75H, m), 2.77 (0.25H, d, J¼15.2 Hz), 2.84 (0.75H, d,
J¼15.8 Hz), 2.92 (0.75H, s), 2.96 (2.25H, s), 2.97 (0.75H, s), 3.03
(2.25H, s). MS m/z (%) 265 (Mþ, 94), 222 (18), 138 (25), 87 (85), 72
(100), 55 (14). Calcd for C17H31NO: M, 265.2405. Found: m/z
265.2404.
3.41. 2-Bicyclo[3.1.0]hex-1-yl-N,N-dimethylacetamide (22a)
To a flame-dried flask was added dry toluene (3.0 mL) followed
by i-PrMgCl (in ether; 0.5 mmol; 5.0 equiv) at ꢀ78 ꢁC. A solution of
adduct 21a (34 mg; 0.1 mmol) in toluene (2.0 mL) was added to the
solution of Grignard reagent dropwise with stirring and the re-
action mixture was slowly allowed to warm to 0 ꢁC for 2 h. The
reaction was quenched with satd aq NH4Cl and the whole mixture
was extracted with CHCl3. As the product 22a and the produced
isopropyl p-tolyl sulfoxide were very difficult to separate by silica
gel chromatography, the sulfoxide was oxidized to sulfone. Thus,
CHCl3 was evaporated and the residue was dissolved in THF
(1.0 mL) and m-CPBA (0.12 mmol; 1.2 equiv) was added to the so-
lution at room temperature. The reaction mixture was stirred for
60 min. The reaction was quenched with satd aq Na2SO3 and the
whole mixture was extracted with CHCl3 and the organic layer was
washed with 5% aq NaOH. The product was purified by silica gel
column chromatography to afford 15.8 mg (93%) of 22a as a color-
less oil. IR (neat) 2927, 2859, 1644 (CO), 1452, 1396, 1267, 1132,
3.46. 2-Bicyclo[13.1.0]hexadec-1-yl-N,N-dimethylacetamide
(22f)
Colorless oil (3:1 mixture of two diastereomers); IR (neat) 2927,
1651 (CO), 1461, 1393, 1265, 1137, 753 cmꢀ1; 1H NMR
d 0.06 (0.25H,
s), 0.22 (0.75H, s), 0.48–0.68 (3H, m), 1.15–1.76 (24.25H, m), 1.90
(0.75H, d, J¼15.0 Hz), 2.04–2.11 (0.75H, m), 2.18 (0.25H, d,
J¼15.0 Hz), 2.54 (0.25H, d, J¼15.0 Hz), 2.77 (0.75H, d, J¼15.7 Hz),
2.92 (0.75H, s), 2.96 (2.25H, s), 2.98 (0.75H, s), 3.03 (2.25H, s). MS
m/z (%) 307 (Mþ, 38), 264 (11),138 (12), 87 (71), 72 (100), 55 (26), 41
(29). Calcd for C20H37NO: M, 307.2873. Found: m/z 307.2880.
Acknowledgements
This work was supported by a Grant-in-Aid for Scientific Re-
search No. 19590018 from the Ministry of Education, Culture,
Sports, Science and Technology, Japan, which is gratefully
acknowledged.
1022 cmꢀ1
;
1H NMR
d
0.34 (1H, dd, J¼8.0, 5.1 Hz), 0.48 (1H, t,
J¼4.5 Hz), 1.10 (1H, quintet, J¼4.1 Hz), 1.16–1.23 (1H, m), 1.55–1.61
(2H, m),1.67 (1H, dd, J¼12.3, 7.9 Hz),1.75–1.82 (1H, m),1.84 (1H, dd,
J¼11.1, 7.40 Hz), 2.51 (1H, d, J¼15.0 Hz), 2.60 (1H, d, J¼15.0 Hz), 2.94
(3H, s), 3.00 (3H, s). MS m/z (%) 167 (Mþ, 21), 95 (12), 87 (42), 72
(100). Calcd for C10H17NO: M, 167.1309. Found: m/z 167.1311.
References and notes
1. Some monographs and reviews concerning chemistry of carbenes and carbe-
noids: (a) Kirmse, W. Carbene Chemistry; Academic: New York, NY, 1971; (b)
Dorwald, F. Z. Metal Carbenes in Organic Synthesis; Wiley-VCH: Weinheim, 1999;
(c) Carbene Chemistry; Bertrand, G., Ed.; Marcel Dekker: New York, NY, 2002; (d)
Kobrich, G. Angew. Chem., Int. Ed. Engl. 1972, 11, 473; (e) Stang, P. J. Chem. Rev.
1978, 78, 383; (f) Burke, S. D.; Grieco, P. A. Org. React. 1979, 26, 361; (g) Schaefer,
H. F., III. Acc. Chem. Res. 1979, 12, 288; (h) Wynberg, H.; Meijer, E. W. Org. React.
1982, 29, 1; (i) Taylor, K. G. Tetrahedron 1982, 38, 2751; (j) Oku, A.; Harada, T.
J. Synth. Org. Chem. Jpn. 1986, 44, 736; (k) Oku, A. J. Synth. Org. Chem. Jpn. 1990,
48, 710; (l) Adams, J.; Spero, D. M. Tetrahedron 1991, 47, 1765; (m) Padwa, A.;
Weingarten, M. D. Chem. Rev. 1996, 96, 223; (n) Zaragoza, F. Tetrahedron 1997,
53, 3425; (o) Kirmse, W. Angew. Chem., Int. Ed. 1997, 36, 1164; (p) Braun, M.
Angew. Chem., Int. Ed. 1998, 37, 430; (q) Mehta, G.; Muthusamy, S. Tetrahedron
2002, 58, 9477; (r) Muller, P. Acc. Chem. Res. 2004, 37, 243; (s) Knorr, R. Chem.
Rev. 2004, 104, 3795.
3.42. 2-Bicyclo[4.1.0]hept-1-yl-N,N-dimethylacetamide (22b)
Colorless oil; IR (neat) 2924, 1652 (CO), 1452, 1394, 1266,
1137 cmꢀ1
;
1H NMR
d
0.30 (1H, t, J¼5.2 Hz), 0.45 (1H, dd, J¼9.2,
4.7 Hz), 0.75–0.83 (1H, m),1.10–1.40 (4H, m), 1.55–1.61 (1H, m), 1.67
(1H, ddd, J¼5.4, 7.8, 13.4 Hz), 1.78 (1H, ddd, J¼4.8, 6.9, 12.1 Hz), 1.96
(1H, sextet, J¼6.6 Hz), 2.24 (1H, d, J¼15.4 Hz), 2.38 (1H, d,
J¼15.4 Hz), 2.94 (3H, s), 2.97 (3H, s). MS m/z (%) 181 (Mþ, 28), 138
(18), 109 (12), 87 (93), 72 (100), 45 (29). Calcd for C11H19NO: M,
181.1467. Found: m/z 167.1471.

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2. Some reviews concerning carbon–hydrogen insertion reaction: (a) Padwa, A.;
Krumpe, K. E. Tetrahedron 1992, 48, 5385; (b) Sulikowski, G. A.; Cha, K. L.;
Sulikowski, M. M. Tetrahedron: Asymmetry 1998, 9, 3145; (c) Davies, H. M. L.;
Beckwith, R. E. J. Chem. Rev. 2003, 103, 2861; (d) Davies, H. M. L.; Loe, O. Syn-
thesis 2004, 2595; (e) Davies, H. M. L. Angew. Chem., Int. Ed 2006, 45, 6422.
3. Satoh, T.; Kondo, A.; Musashi, J. Tetrahedron 2004, 60, 5453.
6. (a) Satoh, T.; Takano, K.; Ota, H.; Someya, H.; Matsuda, K.; Koyama, M. Tetra-
hedron 1998, 54, 5557; (b) Satoh, T.; Kawashima, T.; Takahashi, S.; Sakai, K.
Tetrahedron 2003, 59, 9599.
7. (a) Satoh, T.; Sugiyama, S.; Kamide, Y.; Ota, H. Tetrahedron 2003, 59, 4327; (b)
Satoh, T.; Kamide, Y.; Sugiyama, S. Tetrahedron 2004, 60, 11805; (c) Sugiyama, S.;
Satoh, T. Tetrahedron: Asymmetry 2005, 16, 665.
4. Satoh, T.; Musashi, J.; Kondo, A. Tetrahedron Lett. 2005, 46, 599.
5. Preliminary results of this study were reported as a communication: Satoh, T.;
Ogata, S.; Wakasugi, D. Tetrahedron Lett. 2006, 47, 7249.
8. Kido, M.; Sugiyama, S.; Satoh, T. Tetrahedron: Asymmetry 2007, 18, 1934.
9. Ogata, S.; Masaoka, S.; Sakai, K.; Satoh, T. Tetrahedron Lett. 2007, 48, 5017.
10. Satoh, T.; Oohara, T.; Ueda, Y.; Yamakawa, K. J. Org. Chem. 1989, 54, 3130.