Alkenylation of thiophenes and furans at the 2-position and a synthesis of allenes conjugated with α,β-unsaturated ester with magnesium alkylidene carbenoids

Article abstract of DOI:10.1016/j.tet.2009.02.019

The reaction of 1-chlorovinyl p-tolyl sulfoxides, derived from ketones and chloromethyl p-tolyl sulfoxide, with i-PrMgCl at -78 °C gave magnesium alkylidene carbenoids. Treatment of the magnesium carbenoids with 2-lithiothiophenes and 2-lithiofurans resul

Full text of DOI:10.1016/j.tet.2009.02.019

Tetrahedron 65 (2009) 3509–3517
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Alkenylation of thiophenes and furans at the 2-position and a synthesis
of allenes conjugated with
alkylidene carbenoids
a
,b
-unsaturated ester with magnesium
*
Natsuki Mori, Kazumi Obuchi, Takashi Katae, Jo Sakurada, 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:
Received 21 January 2009
Received in revised form 10 February 2009
Accepted 10 February 2009
Available online 13 February 2009
The reaction of 1-chlorovinyl p-tolyl sulfoxides, derived from ketones and chloromethyl p-tolyl sulfoxide,
with i-PrMgCl at ꢀ78 ꢁC gave magnesium alkylidene carbenoids. Treatment of the magnesium carbe-
noids with 2-lithiothiophenes and 2-lithiofurans resulted in the formation of 2-alkenylated thiophenes
and furans, respectively, in good to high yields. The intermediates of these reactions were found to be
alkenylmagnesium, which could be trapped with several electrophiles to afford thiophenes and furans
bearing a fully substituted alkene at the 2-position. Treatment of the magnesium alkylidene carbenoids
Keywords:
with 2-lithio-5-methoxyfuran afforded allenes conjugated with
a,b-unsaturated methyl ester in
Magnesium carbenoid
Magnesium alkylidene carbenoid
Thiophene
Furan
Alkenylation
moderate yields. These procedures offer a new and versatile one-pot synthesis of 2-alkenylthiophenes, 2-
alkenylfurans, and allenes conjugated with
sulfoxides.
a
,b
-unsaturated methyl ester from 1-chlorovinyl p-tolyl
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
alkylidene carbenoids 3 were found to be stable at low tem-
perature4,5 and reacted with phenylmagnesium bromide to give
phenylated alkenylmagnesium intermediate 4, which was able to
be trapped with electrophiles to afford fully substituted styrene
derivatives 5 in good yields.5
In continuation of our interest in the chemistry of magnesium
alkylidene carbenoids in organic synthesis, we investigated the
reaction of 3 with lithiated heteroaromatic compounds and found
that the reaction of 3 with 2-lithiothiophenes and 2-lithiofurans
gave alkenylmagnesium intermediates bearing thiophenes and
furans, respectively, 6 in good to high yields (Scheme 2).6 These
intermediates were found to be trapped with several electrophiles
to afford thiophenes and furans 7 bearing fully substituted olefins
at the 2-position in good yields. Very interesting reaction was found
Carbenes and carbenoids are obviously one of the most in-
teresting highly reactive carbon species in organic synthesis;
however, in particular case, they are too reactive to be controlled.1
In fact, methylene must be classed as the most indiscriminate re-
active species known in organic chemistry.2 In this decade, we have
studied the chemistry of magnesium carbenoids as more stable
carbenoid species and we have reviewed our work.3
For example, as shown in Scheme 1, treatment of 1-chloro-
vinyl p-tolyl sulfoxides 2, derived from ketones 1 and chloro-
methyl p-tolyl sulfoxide, with phenylmagnesium bromide
resulted in the formation of magnesium alkylidene carbenoids 3
by the sulfoxide–magnesium exchange reaction. The magnesium
R1
R2
E
R1
R2
MgBr
R1
R2
Cl
R1
R2
R1
R2
Cl
TolS(O)CH2Cl
in three steps
PhMgBr
Electrophile
PhMgBr
O
MgBr
S(O)Tol
3
1
5
2
4
Scheme 1.
from the reaction of 3 with 2-lithio-5-methoxyfuran. Thus, the
reaction gave alkenylmagnesium intermediate 8, which afforded
allenes conjugated with a,b-unsaturated methyl ester 9 in moder-
ate to good yields. In this paper, we report in detail the above-
mentioned reactions.
* Corresponding author. Fax: þ81 3 52614631.
E-mail address: tsatoh@rs.kagu.tus.ac.jp (T. Satoh).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.02.019

3510
N. Mori et al. / Tetrahedron 65 (2009) 3509–3517
X
Li
R1
R2
Cl
R1
R2
MgCl
X
R1
R2
E
R1
R2
Cl
Electrophile
R
i-PrMgCl
X
R
X = S, O
MgCl
S(O)Tol
2
3
7
6
R
O
Li
OCH3
R1
R2
Cl
R1
R2
MgCl
O
R1
H
OCH3
R2
MgCl
COOCH3
9
3
8
Scheme 2.
S
Li
1) t - BuMgCl (0.13 eq)
2) i - PrMgCl (2.8 eq)
Cl
MgCl
H
Cl
O
O
O
(3 eq)
S
Toluene-THF (9:1),
-78 ~ -10 °C
Toluene, -78 °C
O
S(O)Tol
10
78%
12a
11
Scheme 3.
2. Results and discussion
the reaction mixture was slowly allowed to warm to ꢀ10 ꢁC.
Fortunately, the desired reaction took place to afford 2-alkenyl-
thiophene 12a in 60% yield.
2.1. Alkenylation of thiophenes at the 2-position with
magnesium alkylidene carbenoids
In order to improve the yield of the product 12a, amount of
i-PrMgCl, solvent, and additive were investigated as reported in
the preliminary letter6 and a mixture of toluene–THF (9:1) was
found to be the solvent of choice and use of 2.8 equiv of
i-PrMgCl was found to be suitable to the reaction and alkeny-
lated thiophene 12a was obtained in 78% yield (Scheme 3). As
the methods for obtaining alkenylated thiophenes are quite
limited,8 the procedure presented herein was thought to be
useful to a synthesis of 2-alkenylthiophenes. We investigated
the generality of this reaction by using the above-mentioned
conditions, and the results are summarized in Table 1.
At first, 1-chlorovinyl p-tolyl sulfoxide 10 was synthesized
from cyclohexane-1,4-dione mono ethylene ketal in three steps in
high overall yield (Scheme 3).5,7 To a solution of 10 in THF was
added t-BuMgCl (0.13 equiv) to remove a trace of moisture in the
reaction mixture. To this solution was added i-PrMgCl (2.8 equiv)
at ꢀ78 ꢁC. Magnesium alkylidene carbenoid 11 was generated
instantaneously. A solution of 2-lithiothiophene (3 equiv), gener-
ated from thiophene with n-BuLi in THF, was added to a solution
of the magnesium alkylidene carbenoid through a cannula and
Table 1
Table 2
Reaction of magnesium alkylidene carbenoid 11 with 2-lithiothiophenes
Reaction of alkenylmagnesium intermediate 13 with electrophiles to give thio-
phenes bearing a fully substituted olefin at the 2-position 14
Entry
1
2-Lithiothiophenea
Product/12
Yield/%
67b
S
H
O
O
Li
1) t - BuMgCl (0.13 eq)
2) i - PrMgCl (2.8 eq)
S
Cl
Li
O
O
(3 eq)
S
10
Toluene, -78 °C
Toluene-THF (9:1)
-78 ~ -10 °C
MgCl
11
12b
Electrophile
cat. CuI
MgCl
S
H
O
O
O
E
S
O
S
Li
CH3
S
CH3
2
3
77
80
O
-10 °C ~ r.t., then
r.t. 1 h
O
12c
14
13
H
O
Entry
Electrophile (equiv)
CuI (mol %)
14
S
Li
OCH3
S
OCH3
E
Yield/%
O
1
2
3
4
5
6
7
8
CH3OD
CH3I (3)
None
5
5
5
5
5
D
CH3
14a
14b
14c
14d
dc
78a
72
12d
CH3CH2I (10)
CH2]CHCH2I (3)
(CH3)2CHI (10)
PhCH2Br (3)
ClCOOC2H5 (10)
I2 (10)
CH2CH3
CH2CH]CH2
CH(CH3)2
CH2Ph
COOC2H5
I
69b
67
H
O
O
S
Li
Cl
S
Cl
4
80
14e
14f
14g
72
70
71
None
None
12e
a
a
All 2-lithiothiophenes were generated from the corresponding thiophenes with
Deuterium content 97%.
The reaction mixture was stirred at room temperature for 3 h.
Compound 12a was obtained as a main product.
b
c
n-BuLi.
b
2-Lithiobenzothiophene was generated with t-BuLi.

N. Mori et al. / Tetrahedron 65 (2009) 3509–3517
3511
Table 3
2-Lithiobenzothiophene was generated from benzothiophene
with t-BuLi in a mixture of toluene–THF, and it was treated with
magnesiumalkylidene carbenoid 11, generated from 10 with i-PrMgCl
in toluene, to give the desired 2-alkenylated benzothiophene 12b in
67% yield (entry 1). 2-Lithiothiophenes bearing an electron-donating
group at the 5-position gave the desired products 12c and 12d in
about 80% yields (entries 2 and 3). 2-Lithiothiophene bearing a chlo-
rine atom at the 5-position gave the desired product 12e without any
problem (entry 4). From these results, generality of this reaction was
thought to be verified.
Reaction of magnesium alkylidene carbenoid 11 with 2-lithiothiophenes followed
by iodomethane to give thiophenes having a fully substituted olefin at the 2-position
15
CH3
S
O
O
1) 2-Lithiothiophenes
2) CH3I, CuI (5 mol%)
11
15
R
Entry
2-Lithiothiophene
15
On the bases of our previous investigations,5,9 the intermediate
of this reaction was thought to be alkenylmagnesium 13 (Table 2).
To ascertain that the intermediate was the expected alkenyl-
magnesium, the reaction of magnesium alkylidene carbenoid 11
with 2-lithiothiophene was quenched with CH3OD. This reaction
afforded 2-alkenylthiophene bearing a deuterium at the olefin
carbon 14a (E¼D) in 78% yield with 97% deuterium incorporation
(Table 2, entry 1). From this result, the intermediate of this reaction
was confirmed to be alkenylmagnesium 13.
It was thought that if this alkenylmagnesium intermediate 13
could be trapped with electrophiles, a new method for a synthesis
of thiophenes bearing a fully substituted olefin would be achieved.
To this end, iodomethane (10 equiv) was added to the reaction
mixture. This reaction gave the methylated product 14b (E¼CH3);
however, the yield was not satisfactory (54%). After some
investigations, Cu(I) iodide was found to be the effective catalyst in
this reaction. Thus, after generation of the intermediate 13, Cu(I)
iodide (5 mol %) followed by iodomethane (3 equiv) was added to
the reaction mixture at ꢀ10 ꢁC and the reaction mixture was slowly
allowed to warm to room temperature. The stirring was continued
for 1 h at room temperature to give the desired methylated product
14b in much better 72% yield (entry 2).
The ethylation reaction required 10 equiv of iodoethane and
much longer reaction time to give the desired product 14c in 69%
yield (entry 3). Allyl iodide, benzyl bromide worked well; however,
2-iodopropane did not give the desired product at all (entries 4–6).
Ethyl chloroformate and iodine gave ethoxycarbonylated and io-
dinated products, 14f and 14g, respectively, in good yields (entries 7
and 8). Unfortunately, benzaldehyde and acetone did not afford the
expected adduct but the protonated product 12a. The reaction with
benzoyl chloride gave a complex mixture.
In order to verify that this procedure could be applicable to
other thiophenes, the reaction of magnesium alkylidene carbenoid
11 with 2-lithiothiophenes followed by iodomethane was carried
out and the results are summarized in Table 3. Comparing the
results in Table 3 with those in Table 1, the yields for the methyl-
ation of 11 with iodomethane giving 15a–15d are high (86–97%).
From the results shown in Table 3, it is verified that the method
mentioned above is applicable to various thiophenes.
Yield/%
58
CH3
O
O
S
Li
Li
S
1
15a
CH3
S
O
O
S
CH3
CH3
2
3
75
70
15b
CH3
S
O
S
Li
OCH3
OCH3
O
15c
CH3
S
O
O
S
Li
Cl
Cl
4
77
15d
Table 4
Synthesis of 2-alkenylthiophenes 16 from 1-chlorovinyl p-tolyl sulfoxides 2 with 2-
lithiothiophene
S
Li
1) t - BuMgCl
R1
R2
Cl
R1
R2
H
(3 eq)
2) i - PrMgCl
S
Toluene-THF
S(O)Tol
-78 ~ -10 °C
2
16
Entry
1-Chlorovinyl p-tolyl sulfoxide
2-Alkenylthiophene 16
E/Z
Yield/%
63
H
Cl
15
S
1
2
d
d
S(O)Tol
16a
2a
H
Cl
S
72
60
S(O)Tol
2b
16b
H3C
Ph
16c (Z)
Ph
H3C
16d (E)
H
H3C
Ph
Cl
S
S
Next, generality of this reaction was investigated using various
1-chlorovinyl p-tolyl sulfoxides with 2-lithiothiophene and the
results are summarized in Table 4. 1-Chlorovinyl p-tolyl sulfoxides
prepared from cyclopentadecanone and cyclohexanone gave the
desired products 16a and 16b, respectively, in good yields (entries 1
and 2). Low stereospecificity was observed in the reaction with
geometrical isomers 2c and 2d (entries 3 and 4). E-Vinyl sulfoxide
2c gave Z-olefin 16c as main product. In contrast to this, Z-vinyl
sulfoxide 2d mainly gave E-olefin 16d.
3
4
34/66
81/19
S(O)Tol
2c (E)
H
Ph
Cl
73
H3C
S(O)Tol
2d (Z)
O
Li
1) t - BuMgCl (0.13 eq)
2) i - PrMgCl (2.8 eq)
Cl
Cl
H
O
O
O
O
(3 eq)
O
-78 ~ -10 °C
82%
THF, -78 °C
MgCl
S(O)Tol
10
11
17a
Scheme 4.

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N. Mori et al. / Tetrahedron 65 (2009) 3509–3517
Table 5
2.2. Alkenylation of furans at the 2-position with magnesium
alkylidene carbenoids
Reaction of 1-chlorovinyl p-tolyl sulfoxide 10 with Grignard reagents followed by 2-
lithiofurans to give furans bearing an olefin at the 2-position 17
O
Li
As an extension of the above-mentioned chemistry, we in-
vestigated the reaction of magnesium alkylidene carbenoid 11 with
2-lithiofurans (Scheme 4). Thus, 1-chlorovinyl p-tolyl sulfoxide 10
was treated with t-BuMgCl followed by i-PrMgCl in THF at ꢀ78 ꢁC
to give magnesium alkylidene carbenoid 11. A solution of 2-lithio-
furan (generated from furan with n-BuLi in THF; 3 equiv) was added
to the solution of 11 and the temperature of the reaction mixture
was slowly allowed to warm to ꢀ10 ꢁC. This reaction gave the de-
sired 2-alkenylfuran 17a in 82% yield. We investigated to find the
better conditions for the formation of 17a; however, the reaction
conditions carried out at the first time proved to be the best.
Next, generality of this reaction was studied by using vari-
ous 2-lithiofurans and the results are summarized in Table 5.
All 2-lithiofurans were generated easily with n-BuLi. As shown
in Table 5, benzofuran and the furans having an electron-do-
nating group gave the desired products 17b–17e in 60–70%
yields (entries 1–4). On the other hand, 2-lithiofuran bearing
an electron-withdrawing group gave the product 17f in much
worse yield (entry 5). Comparing the results in Table 5 with
those in Table 3, 2-lithiothiophenes gave somewhat better
yields in this reaction.
1) t - BuMgCl (0.13 eq)
Cl
(3 eq)
-78 ~ -10 °C
O
O
2) i - PrMgCl (2.8 eq)
R
10
THF, -78 °C
MgCl
11
H
O
O
O
R
17
Entry
1
2-Lithiofuran
Product/17
Yield/%
72
H
O
O
O
Li
O
17b
H
O
O
O
O
Li
Li
CH3
CH3
O
O
CH3
2
68
60
62
17c
H
O
O
CH3
CH3
The intermediate of this reaction was again found to be the
alkenylmagnesium 18 (Table 6). Thus, quenching the reaction of 11
with 2-lithiofuran with CH3OD gave deuterated alkenylfuran 19a in
78% yield with 96% deuterium content (Table 6, entry 1). In the
same way described above, the intermediate 18 could be trapped
3
CH3
17d
H
O
O
Li
SCH3
4a
O
SCH3
with various electrophiles to afford furans bearing
a fully
O
substituted alkene at the 2-position. The reaction conditions and
the results are summarized in Table 6.
17e
H
O
Alkylation of 18 with haloalkanes proceeded well in the pres-
ence of Cu(I) iodide to afford 19b–19e in good yields (entries 2–5).
Benzaldehyde gave the adduct 19g in 73% yield. Ethyl chloro-
formate gave the desired product 19f in moderate yield (entry 6);
however, benzoyl chloride only gave a complex mixture (entry 8).
The reaction with iodine gave the desired alkenyl iodide 19h in
good yield (entry 9).
O
Li
SO2Ph
O
5b
44
SO2Ph
O
17f
a
2-Methylthiofuran was synthesized by Cohen’s procedure; Nolan, S. M.; Cohen,
T. J. Org. Chem. 1981, 46, 2473.
b
2-Phenylsulfonylfuran was derived from 2-phenylthiofuran with m-CPBA.
Finally, generality of the reaction of magnesium alkylidene
carbenoids with 2-lithiofurans was investigated by using some
Table 6
Reaction of alkenylmagnesium intermediate 18 with electrophiles to give furans bearing a fully substituted olefin 19
O
Li
1) t - BuMgCl (0.13 eq)
MgCl
Cl
O
O
(3 eq)
THF, Temp.
2) i - PrMgCl (2.8 eq)
10
THF, -78 °C
11
MgCl
O
E
O
O
O
O
Electrophile, cat. CuI
Conditions
O
19
18
Entry
Electrophile (equiv)
CuI (mol %)
E
Temp
Conditions
19
Yield/%
1
2
3
4
5
6
7
8
9
CH3OD
CH3I (6)
None
5
5
5
5
None
None
None
None
D
CH3
ꢀ78 to ꢀ10 ꢁ
C
ꢀ10 ꢁC to rt, 1 h
ꢀ10 ꢁC to rt, 1 h
ꢀ10 ꢁC to rt, 2 h
ꢀ10 ꢁC to rt, 1 h
ꢀ30 ꢁC to rt, 1 h
ꢀ30 ꢁC to rt, 2 h
ꢀ30 to ꢀ15 ꢁC, 20 min
ꢀ10 ꢁC to rt, 1 h
ꢀ10 ꢁC to rt, 1 h
19a
19b
19c
19d
19e
19f
78a
79
67
75
73
62
73
db
70
ꢀ78 to ꢀ10 ꢁ
ꢀ78 to ꢀ10 ꢁ
ꢀ78 to ꢀ10 ꢁ
ꢀ78 to ꢀ30 ꢁ
ꢀ78 to ꢀ30 ꢁ
C
C
C
C
C
CH3CH2I (6)
CH2]CHCH2I (3)
PhCH2Br (6)
ClCOOC2H5 (10)
PhCHO (10)
PhCOCl (10)
I2 (10)
CH2CH3
CH2CH]CH2
CH2Ph
COOC2H5
CH(Ph)OH
COPh
ꢀ78 to ꢀ30 ꢁC
ꢀ78 to ꢀ10 ꢁC
19g
I
ꢀ78 to ꢀ10 ꢁ
C
19h
a
Deuterium content 96%.
A complex mixture was obtained.
b

N. Mori et al. / Tetrahedron 65 (2009) 3509–3517
3513
Table 7
Table 8
Synthesis of 2-alkenylfurans 20 from 1-chlorovinyl p-tolyl sulfoxides 2 with 2-
Synthesis of allenes conjugated with
a
,b
-unsaturated methyl esters 25 from 1-
lithiofuran
chlorovinyl p-tolyl sulfoxides 2 with 2-lithio-5-methoxyfuran
O
O
OCH3
(3 eq)
Li
Li
1) t - BuMgCl
1) t - BuMgCl
2) i - PrMgCl
THF, -78 °C
R1
R2
Cl
R1
R2
Cl
R1
R2
H
R1
R2
H
(3 eq)
2) i - PrMgCl
H
O
THF, -78 °C
THF
-78 ~ -10 °C
THF
-78 ~ -10 °C
S(O)Tol
S(O)Tol
OCH3
2
2
H
20
25
O
Entry
1-Chlorovinyl p-tolyl sulfoxide
2-Alkenylfuran 20
Entry 1-Chlorovinyl p-tolyl
Allene 25
E/Z
Yield/%
57
sulfoxide
Yield/%
54
H
O
Cl
15
1
d
d
H
S(O)Tol
Cl
15
H
20a
15
2a
1
OCH3
S(O)Tol
H
H
H
O
25a
Cl
2a
Cl
S(O)Tol
2b
Cl
S(O)Tol
O
2
3
56
74
S(O)Tol
H
2b
20b
2
3
54
45
OCH3
OCH3
H
25b
H3C
Ph
H
H3C
Ph
Cl
O
O
O
42/58
82/18
H3C
Ph
H
S(O)Tol
H3C
Ph
H
2c (E)
20c (Z)
Ph
H3C
20d (E)
H
25c
2c (E)
O
H
Ph
Cl
4
73
Ph
Cl
H3C
S(O)Tol
4
40
2d (Z)
H3C
S(O)Tol
2d (Z)
25c
1-chlorovinyl p-tolyl sulfoxides and 2-lithiofuran and the results
are summarized in Table 7. Quite similar stereospecificity was
observed in the reaction with 2c and 2d (entries 3 and 4;
compare the results in Table 4).
NMR showed signals at
1H NMR showed three olefinic protons
J¼15.6 Hz), 7.18 (1H, dd, J¼15.6, 11.0 Hz). From the spectral data, an
allene conjugated with -unsaturated methyl ester was
d
206.5 (allene) and
d 167.2 (ester carbonyl).
d
5.82 (1H, m), 5.85 (1H, d,
a,b
determined to be the structure of the product 24a.
A plausible mechanism for the reaction is shown in Scheme 5.
Thus, 2-lithio-5-methoxyfuran attacks the carbenoid carbon to
give alkenylmagnesium intermediate 21. The anion would cleave
the C–O bond of the furan ring10 to afford 1,2,3-triene conjugated
with enolate 22. This triene intermediate must be unstable and
transfer of the charge on the oxygen to the allenic carbon gives
intermediate 23, which is protonated to give product 24a. When
this reaction was quenched with CH3OD, deuterated allene 24b
was obtained with perfect deuterium incorporation.
2.3. Synthesis of allenes conjugated with a,b-unsaturated
methyl ester by the reaction of magnesium alkylidene
carbenoids with 2-lithio-5-methoxyfuran
Very interesting reaction was found from the reaction of mag-
nesium alkylidene carbenoid with 2-lithio-5-methoxyfuran
(Scheme 5). Thus, the reaction of magnesium alkylidene carbenoid
11 with 2-lithio-5-methoxyfuran under the same conditions as
described above gave an unexpected product in 67% yield. Infrared
absorption of the product showed 1947 cmꢀ1 (allene) and
As we recognized that this reaction is quite useful for a synthesis
1709 cmꢀ1 (carbonyl absorption for an
a,
b
-unsaturated ester). 13C
of allenes conjugated with
a,
b-unsaturated esters, generality of this
O
OCH3
(3 eq)
THF, -78 ~ -10 °C
Li
MgCl
Cl
Cl
O
O
O
OCH3
MgCl
MgCl
11
21
O
OCH3
Li
CH3OH
or
R
O
O
MgCl
O
CH3OD
OCH3
O
H
O
67%
OCH3
OCH3
H
22
23
24a R=H
b R=D
(D-content 99 %)
Scheme 5.

3514
N. Mori et al. / Tetrahedron 65 (2009) 3509–3517
reaction was investigated and the results are summarized in Table
8. Both magnesium alkylidene carbenoids derived from 2a (having
a large cyclic chain) and 2b (having a medium sized cyclic chain)
gave expected allenes 25a and 25b, respectively, in the same
moderate yields (entries 1 and 2). The reaction of the magnesium
alkylidene carbenoids derived from the geometrical isomers 2c and
2d gave the same allene 25c in somewhat lower yields (entries 3
and 4). Although the yields of allenes 25 are not satisfactory, this
method is very useful for a short synthesis of allenes conjugated
(19), 91 (14), 77 (8), 55 (8), 42 (11). Calcd for C13H16O2S: M,
236.0869. Found: m/z 236.0864.
4.1.2. 8-Benzo[b]thiophen-2-ylmethylene-1,4-dioxaspiro[4.5]-
decane (12b)
Colorless crystals; mp 112–112.5 ꢁC (AcOEt–hexane); IR (KBr)
2949, 2881, 2865, 1643, 1431, 1379, 1228, 1139, 1116, 1079, 1036, 907,
877, 741, 726 cmꢀ1
;
1H NMR
d
1.77 (2H, t, J¼6.1 Hz), 1.81 (2H, t,
J¼6.2 Hz), 2.47 (2H, t, J¼6.6 Hz), 2.77 (2H, t, J¼6.6 Hz), 4.00 (4H, s),
6.43 (1H, s), 7.09 (1H, s), 7.23–7.34 (2H, m), 7.69 (1H, d, J¼7.1 Hz),
7.76 (1H, d, J¼7.5 Hz). Anal. Calcd for C17H18O2S: C, 71.30; H, 6.34; S,
11.20. Found: C, 71.12; H, 6.15; S, 11.14.
with a,b-unsaturated methyl ester.
3. Conclusion
In conclusion, we have developed a new method for alkenyla-
tion of thiophenes and furans at the 2-position from 1-chlorovinyl
p-tolyl sulfoxide with 2-lithiothiophenes and 2-lithiofurans in one-
pot. This method could be expanded to a synthesis of thiophenes
and furans bearing a fully substituted olefin at the 2-position.
Moreover, a new method for a synthesis of allenes conjugated with
4.1.3. 8-(5-Methylthiophen-2-ylmethylene)-1,4-
dioxaspiro[4.5]decane (12c)
Yellow oil; IR (neat) 2948, 2880, 1648, 1441, 1382, 1233, 1119,
1080, 1034, 906, 794, 685 cmꢀ1 1H NMR
; d 1.71–1.79 (4H, m), 2.39
(2H, t, J¼6.6 Hz), 2.45 (3H, s), 2.67 (2H, t, J¼6.4 Hz), 3.98 (4H, s), 6.27
(1H, s), 6.61 (1H, dd, J¼3.5,1.1 Hz), 6.68 (1H, d, J¼3.4 Hz). MS m/z (%)
250 (Mþ, 100), 221 (25), 206 (9), 205 (18), 189 (22), 177 (9), 163 (28),
149 (34), 135 (18), 111 (21), 99 (21), 91 (13), 77 (9), 59 (9). Calcd for
C14H18O2S: M, 250.1026. Found: m/z 250.1020.
a,b-unsaturated methyl esters was developed by the reaction of
magnesium alkylidene carbenoids with 2-lithio-5-methoxyfuran.
We believe that the method presented herein will contribute to the
synthesis of the products mentioned above and to the chemistry of
magnesium carbenoids.
4.1.4. 8-(5-Methoxythiophen-2-ylmethylene)-1,4-
dioxaspiro[4.5]decane (12d)
4. Experimental
4.1. General
Yellow oil; IR (neat) 2948, 2881, 1548, 1489, 1430, 1207, 1119,
1080,1034, 906, 769, 684 cmꢀ1; 1H NMR
d
1.73 (2H, t, J¼7.5 Hz),1.75
(2H, t, J¼7.7 Hz), 2.38 (2H, t, J¼6.6 Hz), 2.63 (2H, t, J¼6.4 Hz), 3.87
(3H, s), 3.98 (4H, s), 6.06 (1H, d, J¼4.0 Hz), 6.16 (1H, s), 6.50 (1H, d,
J¼4.0 Hz). MS m/z (%) 266 (Mþ, 100), 251 (14), 221 (22), 207 (10),
205 (32), 170 (25), 165 (13), 151 (10), 137 (14), 127 (22), 109 (7), 99
(19), 91 (11), 77 (9), 55 (10), 42 (9). Calcd for C14H18O3S: M,
266.0975. Found: m/z 266.0975.
All melting points were measured on a Yanaco MP-S3 apparatus
and are uncorrected. 1H 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 a Perkin–Elmer Spectrum One FT-IR
instrument. Silica gel 60 N containing 0.5% fluorescence reagent
254 and a quartz column were used for column chromatography
and the products having UV absorption were detected by UV irra-
diation. In experiment requiring a dry solvent and reagent, diiso-
propylamine and toluene were distilled from CaH2, and THF was
distilled from diphenylketyl. Compounds 2a, 2b, 2c, 2d and 10 are
known.5
4.1.5. 8-(5-Chlorothiophen-2-ylmethylene)-1,4-
dioxaspiro[4.5]decane (12e)
Colorless oil; IR (neat) 2950, 2881, 1646, 1437, 1120, 1081, 907,
758, 686 cmꢀ1; 1H NMR
d
1.73 (2H, t, J¼6.2 Hz),1.77 (2H, t, J¼6.2 Hz),
2.40 (2H, t, J¼6.6 Hz), 2.62 (2H, t, J¼6.6 Hz), 3.99 (4H, s), 6.20 (1H, s),
6.64 (1H, d, J¼3.8 Hz), 6.78 (1H, d, J¼3.9 Hz). MS m/z (%) 270 (Mþ,
100), 241 (40), 225 (20), 209 (13), 197 (12), 183 (22), 173 (21), 163
(22), 149 (25), 134 (23), 121 (28), 99 (25), 86 (21), 77 (12), 55 (13), 42
(17). Calcd for C13H15O2ClS: M, 270.0479. Found: m/z 270.0476.
4.1.1. 8-Thiophen-2-ylmethylene-1,4-dioxaspiro[4.5]decane (12a)
To a solution of 10 (98.0 mg; 0.3 mmol) in 6 mL of dry toluene
in a flame-dried flask at ꢀ78 ꢁC under argon atmosphere was
added t-BuMgCl (1.0 M solution in THF, 0.04 mL; 0.04 mmol)
dropwise with stirring. After 10 min, i-PrMgCl (2.0 M solution in
THF, 0.42 mL; 0.84 mmol) was added dropwise to the reaction
mixture to give magnesium alkylidene carbenoid 11. In another
flask, n-BuLi (1.65 M solution in hexane, 0.6 mL; 0.99 mmol) was
added dropwise to a solution of thiophene (0.072 mL; 0.9 mmol)
in a mixture of 3 mL of dry toluene and 1 mL of THF at ꢀ78 ꢁC
under argon atmosphere to give 2-lithiothiophene. After 30 min,
this solution was added to a solution of carbenoid 11 through
a cannula. Temperature of the reaction mixture was gradually
allowed to warm to ꢀ10 ꢁC. The reaction was quenched by satd aq
NH4Cl and the whole was extracted with CHCl3. The organic layer
was dried over MgSO4 and concentrated in vacuo. The residue
was purified by silica gel flash column chromatography to give
12a (55 mg; 78%) as colorless oil. IR (neat) 3104, 2949, 2881, 1648,
4.1.6. 8-(1-Thiophen-2-ylethylidene)-1,4-dioxaspiro[4.5]-
decane (14b)
To a solution of 10 (98 mg; 0.3 mmol) in 6 mL of dry toluene
in a flame-dried flask at ꢀ78 ꢁC under argon atmosphere was
added t-BuMgCl (1.0 M solution in THF, 0.04 mL; 0.04 mmol)
dropwise with stirring. After 10 min, i-PrMgCl (2.0 M solution in
THF, 0.42 mL; 0.84 mmol) was added dropwise to the reaction
mixture to give magnesium alkylidene carbenoid 11. In another
flask, n-BuLi (1.65 M solution in hexane, 0.6 mL; 0.99 mmol) was
added dropwise to a solution of thiophene (0.072 mL; 0.9 mmol)
in a mixture of 3 mL of dry toluene and 1 mL of THF at ꢀ78 ꢁC
under argon atmosphere to give 2-lithiothiophene. After 30 min,
this solution was added to a solution of carbenoid 11 through
a cannula. Temperature of the reaction mixture was gradually
allowed to warm to ꢀ10 ꢁC. Copper iodide (2.9 mg; 0.015 mmol)
was added to the reaction mixture and was stirred for 10 min.
Iodomethane (0.056 mL; 0.9 mmol) was added dropwise to the
reaction mixture. The reaction mixture was gradually allowed to
warm to room temperature, and then was stirred for 1 h at room
temperature. The reaction was quenched by satd aq NH4Cl and
the whole was extracted with CHCl3. The organic layer was dried
over MgSO4 and concentrated in vacuo. The residue was purified
1432, 1120, 1082, 907, 761, 693 cmꢀ1 1H NMR
; d 1.76 (4H, dt,
J¼6.5, 5.5 Hz), 2.42 (2H, t, J¼6.6 Hz), 2.70 (2H, t, J¼6.6 Hz), 3.99
(4H, s), 6.36 (1H, s), 6.89 (1H, d, J¼3.4 Hz), 6.97 (1H, dd, J¼5.1,
3.5 Hz), 7.19 (1H, d, J¼5.1 Hz). MS m/z (%) 236 (Mþ, 100), 207 (40),
192 (9), 191 (13), 174 (17), 163 (10), 149 (12), 135 (30), 121 (14), 97

N. Mori et al. / Tetrahedron 65 (2009) 3509–3517
3515
by silica gel flash column chromatography to give 14b (53.9 mg;
4.1.12. 8-(1-Benzo[b]thiophen-2-ylethylidene)-1,4-
72%) as colorless crystals; mp 54.0–54.5 ꢁC (AcOEt–hexane). IR
(KBr) 2947, 2880, 1438, 1364, 1232, 1124, 1097, 1034, 900, 764,
dioxaspiro[4.5]decane (15a)
Colorless crystals; mp 94.5–95 ꢁC (AcOEt–hexane); IR (KBr)
2960, 2934, 2897, 2850, 1438, 1367, 1236, 1179, 1127, 1113, 1087,
693 cmꢀ1
;
1H NMR
d
1.64 (2H, t, J¼6.5 Hz), 1.76 (2H, t, J¼6.7 Hz),
2.04 (3H, s), 2.40 (2H, t, J¼6.6 Hz), 2.47 (2H, t, J¼6.6 Hz), 3.97
(4H, s), 6.76 (1H, dd, J¼3.5, 1.2 Hz), 6.96 (1H, dd, J¼5.1, 3.5 Hz),
7.20 (1H, dd, J¼5.1, 1.1 Hz). MS m/z (%) 250 (Mþ, 100), 235 (21),
221 (26), 205 (15), 191 (25), 173 (15), 163 (22), 149 (47), 135 (27),
121 (12), 99 (23), 86 (18), 77 (11), 55 (10). Calcd for C14H18O2S:
M, 250.1025. Found: m/z 250.1024. Anal. Calcd for C14H18O2S: C,
67.17; H, 7.25; S, 12.81. Found: C, 67.13; H, 7.23; S, 12.78.
1029, 939, 897, 822, 754, 728 cmꢀ1; 1H NMR
d
1.65 (2H, t, J¼6.5 Hz),
1.78 (2H, t, J¼6.5 Hz), 2.09 (3H, s), 2.44 (2H, t, J¼6.1 Hz), 2.50 (2H, t,
J¼6.5 Hz), 3.98 (4H, s), 6.96 (1H, s), 7.24–7.35 (2H, m), 7.70 (1H, d,
J¼7.2 Hz), 7.78 (1H, d, J¼7.9 Hz). Anal. Calcd for C18H20O2S: C, 71.97;
H, 6.71; S, 10.67. Found: C, 71.99; H, 6.73; S, 10.66.
4.1.13. 8-[1-(5-Methylthiophen-2-yl)ethylidene]-1,4-
dioxaspiro[4.5]decane (15b)
4.1.7. 8-(1-Thiophen-2-ylpropylidene)-1,4-dioxaspiro[4.5]-
decane (14c)
Yellow oil; IR (neat) 3061, 2947, 2880, 1443, 1364, 1232, 1124,
1096, 1035, 945, 901, 800, 759, 690 cmꢀ1 1H NMR
; d 1.64 (2H, t,
Colorless crystals; mp 40–40.5 ꢁC (AcOEt–hexane); IR (KBr)
J¼6.5 Hz), 1.74 (2H, t, J¼6.5 Hz), 2.00 (3H, s), 2.41–2.47 (7H, m), 3.97
(4H, s), 6.54 (1H, d, J¼3.4 Hz), 6.59–6.60 (1H, m). MS m/z (%) 264
(Mþ, 100), 249 (20), 235 (16), 220 (29), 219 (23), 205 (23), 187 (17),
177 (30), 163 (60), 149 (32), 125 (20), 111 (14), 99 (35), 86 (21), 77
(13), 55 (14), 42 (13). Calcd for C15H20O2S: M, 264.1183. Found: m/z
264.1187.
2960, 2875, 1366, 1124, 1101, 1035, 694 cmꢀ1; 1H NMR
d 0.96 (3H, t,
J¼7.5 Hz),1.64 (2H, t, J¼6.4 Hz),1.76 (2H, t, J¼6.2 Hz), 2.29–2.47 (6H,
m), 3.97 (4H, s), 6.73 (1H, dd, J¼3.4, 1.1 Hz), 6.96 (1H, dd, J¼5.1,
3.4 Hz), 7.21 (1H, dd, J¼5.1, 1.1 Hz). Anal. Calcd for C15H20O2S: C,
68.14; H, 7.62; S, 12.13. Found: C, 67.50; H, 7.56; S, 11.98.
4.1.14. 8-[1-(5-Methoxythiophen-2-yl)ethylidene]-1,4-
dioxaspiro[4.5]decane (15c)
4.1.8. 8-(1-Thiophen-2-ylbut-3-enylidene)-1,4-
dioxaspiro[4.5]decane (14d)
Yellow oil; IR (neat) 2947, 2882, 1718, 1650, 1553, 1500, 1431,
Colorless oil; IR (neat) 2949, 2880, 1637, 1440, 1247, 1233, 1124,
1364, 1277, 1204, 1124, 1096, 1034, 945, 901, 761 cmꢀ1 1H NMR
;
d
1100,1035, 909, 695 cmꢀ1; 1H NMR
d
1.66 (2H, t, J¼6.4 Hz),1.75 (2H,
1.64 (2H, t, J¼6.5 Hz), 1.73 (2H, t, J¼6.5 Hz), 1.98 (3H, s), 2.43 (2H, t,
t, J¼6.4 Hz), 2.39 (2H, t, J¼6.5 Hz), 2.45 (2H, t, J¼6.5 Hz), 3.14 (2H, d,
J¼6.0 Hz), 3.97 (4H, s), 4.97–5.07 (2H, m), 5.72–5.85 (1H, m), 6.75
(1H, dd, J¼3.5, 1.2 Hz), 6.95 (1H, dd, J¼5.0, 3.4 Hz), 7.19 (1H, dd,
J¼5.3, 1.1 Hz). MS m/z (%) 276 (Mþ, 100), 235 (35), 231 (12), 215 (12),
191 (26), 175 (25), 161 (37), 149 (36), 135 (23), 115 (15), 99 (37), 86
(21), 77 (15), 55 (15), 42 (13). Calcd for C16H20O2S: M, 276.1182.
Found: m/z 276.1175.
J¼6.0 Hz), 2.45 (2H, t, J¼5.3 Hz), 3.86 (3H, s), 3.97 (4H, s), 6.04 (1H,
d, J¼3.8 Hz), 6.36 (1H, d, J¼3.8 Hz). MS m/z (%) 280 (Mþ, 100), 265
(20), 235 (20), 221 (13), 219 (30), 193 (20), 179 (31), 165 (13), 151
(14), 141 (17), 127 (8), 115 (7), 99 (28), 91 (13), 77 (9), 55 (13), 42
(10). Calcd for C15H20O3S: M, 280.1131. Found: m/z 280.1126.
4.1.15. 8-[1-(5-Chlorothiophen-2-yl)ethylidene]-1,4-
dioxaspiro[4.5]decane (15d)
4.1.9. 8-(2-Phenyl-1-thiophen-2-ylethylidene)-1,4-
dioxaspiro[4.5]decane (14e)
Colorless oil; IR (neat) 2948, 2880, 1446, 1365, 1230, 1124, 1096,
1035, 945, 900, 796 cmꢀ1; 1H NMR
d
1.63 (2H, t, J¼6.6 Hz), 1.74 (2H,
Colorless oil; IR (neat) 2950, 2882, 1494, 1453, 1367, 1246, 1232,
1123, 1094, 1034, 944, 904, 850, 756, 697 cmꢀ1; 1H NMR
d 1.70 (2H,
t, J¼6.6 Hz), 1.99 (3H, s), 2.39 (2H, t, J¼6.8 Hz), 2.44 (2H, t, J¼6.7 Hz),
3.97 (4H, s), 6.51 (1H, d, J¼3.8 Hz), 6.76 (1H, d, J¼3.8 Hz). MS m/z (%)
284 (Mþ, 100), 269 (22), 255 (18), 240 (34), 225 (32), 207 (16), 197
(22), 138 (38), 169 (14), 163 (29), 149 (23), 134 (22), 115 (14), 99 (38),
86 (27), 55 (18), 42 (21). Calcd for C14H17O2ClS: M, 284.0637. Found:
m/z 284.0648.
t, J¼6.4 Hz), 1.79 (2H, t, J¼6.4 Hz), 2.44 (2H, t, J¼6.4 Hz), 2.57 (2H, t,
J¼6.4 Hz), 3.77 (2H, s), 3.98 (4H, s), 6.62 (1H, dd, J¼3.5, 1.3 Hz), 6.88
(1H, dd, J¼5.0, 3.5 Hz), 7.10–7.24 (6H, m). MS m/z (%) 326 (Mþ, 100),
235 (59), 211 (45),191 (30), 173 (15), 149 (32), 99 (32), 91 (39). Calcd
for C20H22O2S: M, 326.1340. Found: m/z 326.1341.
4.1.16. 2-(Cyclopentadecylidenemethyl)thiophene (16a)
4.1.10. (1,4-Dioxaspiro[4.5]dec-8-ylidene)thiophen-2-ylacetic acid
ethyl ester (14f)
Colorless oil; IR (neat) 2929, 2856,1459,1349, 854, 689 cmꢀ1; 1H
NMR
d
1.34–1.53 (24H, m), 2.17 (2H, t, J¼8.1 Hz), 2.38 (2H, t,
Yellow oil; IR (neat) 3103, 2953, 2883,1718,1624,1445,1207,1089,
J¼8.1 Hz), 6.39 (1H, s), 6.88 (1H, d, J¼3.4 Hz), 6.97 (1H, dd, J¼5.2,
3.5 Hz), 7.17 (1H, d, J¼5.1 Hz). MS m/z (%) 304 (Mþ, 100), 151 (8), 137
(22), 123 (28), 110 (27), 97 (37), 91 (9), 69 (7), 55 (17), 41 (23), 28
(30), 18 (9). Calcd for C20H32S: M, 304.2223. Found: m/z 304.2229.
700 cmꢀ1; 1H NMR
d
1.26 (3H, t, J¼7.2 Hz), 1.72 (2H, t, J¼6.8 Hz), 1.83
(2H, t, J¼6.8 Hz), 2.44 (2H, t, J¼6.8 Hz), 2.69 (2H, t, J¼6.8 Hz), 3.97 (4H,
s), 4.21 (2H, q, J¼7.2 Hz), 6.88 (1H, dd, J¼3.5, 1.2 Hz), 7.00 (1H, dd,
J¼5.1, 3.5 Hz), 7.29 (1H, dd, J¼5.1,1.2 Hz). MS m/z (%) 308 (Mþ,13), 279
(14), 262 (100), 235 (33), 222 (5), 217 (25), 200 (10),189 (13),173 (12),
161 (10),149 (24),135 (15),121 (18), 99 (21), 86 (23), 77 (10). Calcd for
C16H20O4S: M, 308.1080. Found: m/z 308.1080.
4.1.17. 2-(Cyclohexylidenemethyl)thiophene (16b)
Colorless oil; IR (neat) 2928, 2853, 1446, 1343, 1237, 851,
690 cmꢀ1; 1H NMR
d 1.60–1.61 (6H, m), 2.23–2.29 (2H, m), 2.54 (2H,
m), 6.29 (1H, s), 6.87 (1H, d, J¼3.4 Hz), 6.96 (1H, dd, J¼5.1, 3.6 Hz),
7.16 (1H, dd, J¼5.1, 1.1 Hz). MS m/z (%) 178 (Mþ, 100), 177 (8), 150 (9),
149 (18), 135 (32), 110 (84), 97 (59), 91 (21), 79 (21), 65 (10), 39 (20).
Calcd for C11H14S: M, 178.0815. Found: m/z 178.0812.
4.1.11. 8-(Iodothiophen-2-ylmethylene)-1,4-dioxaspiro[4.5]-
decane (14g)
Colorless crystals; mp 118.5–119 ꢁC (AcOEt–hexane); IR (KBr)
3100, 2942, 2880, 2348, 1425, 1364, 1335, 1232, 1211, 1121, 1076,
1031, 942, 908, 764, 731 cmꢀ1; 1H NMR
d
1.60 (2H, t, J¼6.6 Hz), 1.80
4.1.18. 8-Furan-2-ylmethylene-1,4-dioxaspiro[4.5]decane (17a)
To a solution of 10 (98 mg; 0.3 mmol) in 6 mL of dry THF in
a flame-dried flask at ꢀ78 ꢁC under argon atmosphere was added
t-BuMgCl (1.0 M solution in THF, 0.04 mL; 0.04 mmol) dropwise
with stirring. After 10 min, i-PrMgCl (2.0 M solution in THF,
0.42 mL; 0.84 mmol) was added dropwise to the reaction mix-
ture to give magnesium alkylidene carbenoid 11. In another flask,
(2H, t, J¼6.6 Hz), 2.49 (2H, t, J¼6.6 Hz), 2.72 (2H, t, J¼6.8 Hz), 3.98
(4H, s), 6.92–6.95 (2H, m), 7.26–7.29 (1H, m). MS m/z (%) 362 (Mþ,
10), 235 (100), 191 (9), 173 (10), 149 (50), 121 (22), 77 (9), 55 (9).
Calcd for C13H15O2SI: M, 361.9838. Found: m/z 361.9839. Anal. Calcd
for C13H15O2SI: C, 43.11; H, 4.17; I, 35.03; S, 8.72. Found: C, 43.15; H,
4.08; I, 34.99; S, 8.72.

3516
N. Mori et al. / Tetrahedron 65 (2009) 3509–3517
n-BuLi (1.65 M solution in hexane, 0.6 mL; 0.99 mmol) was added
dropwise to a solution of furan (0.065 mL; 0.9 mmol) in 4 mL of
dry THF at ꢀ50 ꢁC and the reaction mixture was allowed to
warm to ꢀ10 ꢁC under argon atmosphere to give 2-lithiofuran.
This solution was added to a solution of carbenoid 11 through
a cannula at ꢀ78 ꢁC. Temperature of the reaction mixture was
gradually allowed to warm to ꢀ10 ꢁC. The reaction was quenched
by satd aq NH4Cl and the whole was extracted with CHCl3. The
organic layer was dried over MgSO4 and concentrated in vacuo.
The residue was purified by silica gel flash column chromato-
graphy to give 17a (54 mg; 82%) as a colorless oil. IR (neat) 2949,
2884, 1717, 1683, 1622, 1445, 1371, 1275, 1120, 1083, 1034, 906,
d, J¼7.2 Hz), 7.52–7.60 (2H, m), 7.60–7.63 (1H, m), 7.99–8.01 (2H,
m). MS m/z (%) 360 (Mþ, 62), 331 (17), 316 (100), 219 (48), 191 (94),
174 (21), 125 (80), 99 (41), 77 (97), 51 (55). Calcd for C19H20O5S: M,
360.1029. Found: m/z 360.1029.
4.1.24. 8-(1-Furan-2-ylethylidene)-1,4-dioxaspiro[4.5]decane (19b)
To a solution of 10 (98 mg; 0.3 mmol) in 6 mL of dry THF in
a flame-dried flask at ꢀ78 ꢁC under argon atmosphere was added
t-BuMgCl (1.0 M solution in THF, 0.04 mL; 0.04 mmol) dropwise
with stirring. After 10 min, i-PrMgCl (2.0 M solution in THF,
0.42 mL; 0.84 mmol) was added dropwise to the reaction mixture
to give magnesium alkylidene carbenoid 11. In an another flask,
n-BuLi (1.65 M solution in hexane, 0.6 mL; 0.99 mmol) was added
dropwise to a solution of furan (0.065 mL; 0.9 mmol) in 4 mL of
THF at ꢀ50 ꢁC and the reaction mixture was allowed to warm to
ꢀ10 ꢁC under argon atmosphere to give 2-lithiofuran. This solu-
tion was added to a solution of carbenoid 11 through a cannula at
ꢀ78 ꢁC. Temperature of the reaction mixture was gradually
allowed to warm to ꢀ10 ꢁC. Copper iodide (2.9 mg; 0.015 mmol)
was added to the reaction mixture and was stirred for 10 min.
Iodomethane (0.112 mL; 1.8 mmol) was added dropwise to the
reaction mixture. The reaction mixture was gradually allowed to
warm to room temperature, and then was stirred for 1 h at room
temperature. The reaction was quenched by satd aq NH4Cl and
the whole was extracted with CHCl3. The organic layer was dried
over MgSO4 and concentrated in vacuo. The residue was purified
by silica gel flash column chromatography to give 19b (55.7 mg;
79%) as colorless oil. IR (neat) 2947, 2881, 1496, 1445, 1124, 1099,
735 cmꢀ1
;
1H NMR
d
1.75 (2H, t, J¼6.6 Hz), 1.77 (2H, t, J¼6.6 Hz),
2.40 (2H, t, J¼6.6 Hz), 2.77 (2H, t, J¼6.6 Hz), 3.99 (4H, s), 6.03
(1H, s), 6.17 (1H, d, J¼3.4 Hz), 6.36 (1H, dd, J¼3.1, 1.8 Hz), 7.34
(1H, d, J¼1.8 Hz). MS m/z (%) 220 (Mþ, 100), 191 (43), 158 (17),
133 (25), 99 (51), 77 (15), 55 (21). Calcd for C13H16O3: M,
220.1098. Found: m/z 220.1098.
4.1.19. 8-Benzofuran-2-ylmethylene-1,4-dioxaspiro[4.5]-
decane (17b)
Colorless crystals; mp 60–61 ꢁC (hexane); IR (KBr) 2949, 2863,
1658, 1455, 1378, 1260, 1228, 1183, 1139, 1117, 1080, 1037, 942,
740 cmꢀ1
;
1H NMR
d
1.80 (2H, t, J¼7.6 Hz), 1.81 (2H, t, J¼7.6 Hz),
2.47 (2H, t, J¼6.6 Hz), 2.92 (2H, t, J¼6.6 Hz), 4.01 (4H, s), 6.17 (1H, s),
6.52 (1H, s), 7.17–7.24 (2H, m), 7.43 (1H, d, J¼7.3 Hz), 7.50 (1H, d,
J¼7.6 Hz). MS m/z (%) 270 (Mþ,100), 241 (20), 225 (13), 208 (18),197
(13), 183 (30), 169 (20), 131 (21), 115 (13), 99 (12), 28 (31). Anal.
Calcd for C17H18O3: C, 75.53; H, 6.71. Found: C, 75.37; H, 6.68.
1013, 917, 897, 734 cmꢀ1
;
1H NMR
d
1.70 (2H, t, J¼6.4 Hz), 1.75
(2H, t, J¼6.4 Hz), 1.98 (3H, s), 2.47 (2H, t, J¼6.5 Hz), 2.61 (2H, t,
J¼6.0 Hz), 3.98 (4H, s), 6.14 (1H, d, J¼3.0 Hz), 6.37 (1H, dd, J¼3.3,
2.0 Hz), 7.36 (1H, d, J¼1.8 Hz). MS m/z (%) 234 (Mþ, 100), 220 (10),
219 (21), 205 (20), 189 (15), 175 (30), 157 (18), 147 (22), 133 (27),
119 (20), 99 (28), 91 (38). Calcd for C14H18O3: M, 234.1255. Found:
m/z 234.1259.
4.1.20. 8-(5-Methylfuran-2-ylmethylene)-1,4-
dioxaspiro[4.5]decane (17c)
Colorless oil; IR (neat) 2947, 2882, 1596, 1538, 1444, 1275, 1230,
1120, 1084, 1034, 906, 779, 685 cmꢀ1 1H NMR
; d 1.74 (2H, t,
J¼6.7 Hz), 1.76 (2H, t, J¼6.7 Hz), 2.29 (3H, s), 2.38 (2H, t, J¼6.5 Hz),
2.75 (2H, t, J¼6.5 Hz), 3.99 (4H, s), 5.94 (1H, dd, J¼3.2, 1.2 Hz), 5.96
(1H, s), 6.06 (1H, d, J¼3.1 Hz). MS m/z (%) 234 (Mþ, 100), 205 (25),
189 (18), 173 (23), 147 (37), 133 (17), 119 (14), 95 (29), 43 (39). Calcd
for C14H18O3: M, 234.1255. Found: m/z 234.1262.
4.1.25. 8-(1-Furan-2-ylpropylidene)-1,4-dioxaspiro[4.5]-
decane (19c)
Colorless oil; IR (neat) 2957, 2878, 1718, 1444, 1366, 1274, 1231,
1124, 1102, 1035, 914, 734 cmꢀ1
;
1H NMR
d
0.95 (3H, t, J¼7.5 Hz),
4.1.21. 8-(4,5-Dimethylfuran-2-ylmethylene)-1,4-dioxaspiro[4.5]-
decane (17d)
1.69 (2H, t, J¼6.4 Hz), 1.75 (2H, t, J¼6.8 Hz), 2.37–2.55 (6H, m), 3.98
(4H, s), 6.13 (1H, dd, J¼3.2, 0.6 Hz), 6.37 (1H, dd, J¼3.3, 1.7 Hz), 7.36
(1H, dd, J¼1.7, 0.8 Hz). MS m/z (%) 248 (Mþ, 100), 219 (82), 175 (35),
153 (33), 99 (40), 86 (32). Calcd for C15H20O3: M, 248.1412. Found:
m/z 248.1413.
Colorless oil; IR (neat) 2946, 2880, 1629, 1444, 1247, 1228, 1119,
1083, 1034, 945, 906 cmꢀ1 1H NMR
; d 1.71–1.77 (4H, m), 1.92 (3H,
s), 2.20 (3H, s), 2.37 (2H, t, J¼6.4 Hz), 2.73 (2H, t, J¼6.4 Hz), 3.98
(4H, s), 5.92 (1H, s), 5.97 (1H, s). MS m/z (%) 248 (Mþ, 100), 219
(17), 203 (13), 187 (30), 161 (24), 147 (13), 133 (11), 109 (28), 99
(19), 77 (9), 55 (9), 43 (39). Calcd for C15H20O3: M, 248.1411.
Found: m/z 248.1403.
4.1.26. 8-(1-Furan-2-ylbut-3-enylidene)-1,4-dioxaspiro[4.5]-
decane (19d)
Colorless oil; IR (neat) 2950, 2882, 1719, 1637, 1496, 1445, 1366,
1275,1235,1123,1035, 944, 907, 751 cmꢀ1; 1H NMR
d 1.69–1.77 (4H,
4.1.22. 8-(5-Methylsulfanylfuran-2-ylmethylene)-1,4-
dioxaspiro[4.5]decane (17e)
m), 2.44 (2H, t, J¼6.4 Hz), 2.60 (2H, t, J¼6.4 Hz), 3.16 (2H, d,
J¼5.9 Hz), 3.98 (4H, s), 4.93–5.04 (2H, m), 5.72–5.85 (1H, m), 6.16
(1H, d, J¼3.2 Hz), 6.36 (1H, dd, J¼3.3, 1.9 Hz), 7.36 (1H, d, J¼1.9 Hz).
MS m/z (%) 260 (Mþ, 100), 219 (33), 175 (26), 145 (19), 99 (18), 91
(20). Calcd for C16H20O3: M, 260.1413. Found: m/z 260.1411.
Colorless oil; IR (neat) 2948, 2881, 1658, 1485, 1435, 1120, 1083,
1034, 906, 783 cmꢀ1
;
1H NMR
d
1.75 (2H, t, J¼6.0 Hz), 1.77 (2H, t,
J¼6.0 Hz), 2.41 (5H, m), 2.76 (2H, t, J¼6.5 Hz), 3.99 (4H, s), 5.99 (1H,
s), 6.14 (1H, d, J¼3.3 Hz), 6.40 (1H, d, J¼3.3 Hz). MS m/z (%) 266 (Mþ,
100), 222 (14), 205 (27), 147 (13), 142 (30), 127 (15), 99 (74), 86 (23),
55 (18), 32 (17). Calcd for C14H18O3S: M, 266.0976. Found: m/z
266.0975.
4.1.27. 8-(1-Furan-2-yl-2-phenylethylidene)-1,4-dioxaspiro[4.5]-
decane (19e)
Colorless crystals; mp 64.5–65 ꢁC (AcOEt–hexane); IR (KBr)
3149, 3118, 3025, 2970, 2951, 2929, 2881, 2847, 1600, 1494, 1446,
4.1.23. 8-(5-Benzenesulfonylfuran-2-ylmethylene)-1,4-
dioxaspiro[4.5]decane (17f)
1424, 1356, 1233, 1197, 1134, 1099, 1082, 1032, 945, 904, 728 cmꢀ1
;
1H NMR
d
1.70–1.77 (4H, m), 2.51 (2H, t, J¼6.4 Hz), 2.65 (2H, t,
Colorless oil; IR (neat) 2950, 1691, 1655, 1482, 1447, 1330, 1170,
J¼6.4 Hz), 3.80 (2H, s), 3.98 (4H, s), 6.08 (1H, dd, J¼3.3, 0.7 Hz), 6.31
(1H, dd, J¼3.3, 1.8 Hz), 7.10–7.24 (5H, m), 7.33 (1H, dd, J¼1.8,
0.7 Hz). Anal. Calcd for C20H22O3: C, 77.38; H, 7.10. Found: C, 77.39;
H, 7.14.
1145, 1083, 1032, 942, 906, 725 cmꢀ1 1H NMR
; d 1.72 (2H, t,
J¼6.6 Hz), 1.75 (2H, t, J¼6.6 Hz), 2.40 (2H, t, J¼6.6 Hz), 2.68 (2H, t,
J¼6.6 Hz), 3.99 (4H, s), 6.00 (1H, s), 6.24 (1H, d, J¼3.4 Hz), 7.16 (1H,

N. Mori et al. / Tetrahedron 65 (2009) 3509–3517
3517
4.1.28. (1,4-Dioxaspiro[4.5]dec-8-ylidene)furan-2-ylacetic acid
ethyl ester (19f)
1.47 (4H, t, J¼6.8 Hz), 2.05 (4H, dt, J¼6.8, 2.5 Hz), 3.73 (3H, s), 5.84
(1H, d, J¼15.4 Hz), 5.87–5.89 (1H, m), 7.18 (1H, dd, J¼15.4, 11.1 Hz).
MS m/z (%) 318 (Mþ, 50), 287 (12), 259 (22), 219 (12), 178 (9), 152
(92), 137 (30), 105 (53), 93 (100), 41 (78). Calcd for C21H34O2: M,
318.2559. Found: m/z 318.2555.
Colorless oil; IR (neat) 2955, 2885, 1719, 1638, 1446, 1367, 1281,
1245, 1212, 1089, 1033, 946, 927, 901, 752 cmꢀ1; 1H NMR
d 1.28 (3H,
t, J¼7.2 Hz), 1.77 (2H, t, J¼6.4 Hz), 1.82 (2H, t, J¼6.4 Hz), 2.59 (2H, t,
J¼6.6 Hz), 2.64 (2H, t, J¼6.6 Hz), 3.98 (4H, s), 4.25 (2H, q, J¼7.2 Hz),
6.25 (1H, dd, J¼3.3, 0.8 Hz), 6.40 (1H, dd, J¼3.3,1.8 Hz), 7.40 (1H, dd,
J¼1.8, 0.8 Hz). MS m/z (%) 292 (Mþ, 25), 246 (100), 219 (37), 201
(21), 184 (11), 157 (18), 133 (11), 86 (17). Calcd for C16H20O5: M,
292.1310. Found: m/z 292.1312.
4.1.35. 5-Cyclohexylidenepenta-2,4-dienoic acid methyl ester (25b)
Colorless oil; IR (neat) 2932, 2855, 1945, 1716, 1628, 1440, 1299,
1273, 1246, 1193, 1165, 1119, 983, 868 cmꢀ1 1H NMR
; d 1.51–1.66
(6H, m), 2.13–2.17 (4H, m), 3.74 (3H, s), 5.76–5.80 (1H, m), 5.83 (1H,
dd, J¼15.4, 0.6 Hz), 7.19 (1H, dd, J¼15.4, 11.0 Hz). MS m/z (%) 192
(Mþ, 76), 191 (12), 163 (18), 133 (33), 117 (19), 105 (30), 91 (100), 77
(30), 65 (21), 39 (27), 27 (12). Calcd for C12H16O2: M, 192.1148.
Found: m/z 192.1145.
4.1.29. 2-(1,4-Dioxaspiro[4.5]dec-8-ylidene)-2-furan-2-yl-1-
phenylethanol (19g)
Colorless oil; IR (neat) 3430, 2940, 2921, 1648, 1495, 1448, 1236,
1201, 1080, 1058, 1034, 905, 738 cmꢀ1; 1H NMR
d 1.68–1.86 (4H, m),
2.33 (1H, t, J¼7.8 Hz), 2.41 (2H, t, J¼6.5 Hz), 2.58–2.65 (2H, m), 3.98
(4H, s), 5.92–5.94 (2H, m), 6.28 (1H, dd, J¼3.2, 1.9 Hz), 7.20–7.34
(6H, m). MS m/z (%) 326 (Mþ, 45), 308 (100), 236 (23), 222 (96), 133
(33), 105 (80), 91 (40), 77 (80), 55 (30), 42 (22). Calcd for C20H22O4:
M, 326.1517. Found: m/z 326.1521.
4.1.36. 6-Phenylhepta-2,4,5-trienoic acid methyl ester (25c)
Colorless oil; IR (neat) 3026, 2988, 2950, 1930, 1719, 1627, 1598,
1494, 1436, 1302, 1267, 1246, 1167, 1114, 1066, 1027, 981, 872, 760,
693 cmꢀ1 1H NMR
; d 2.15 (3H, s), 3.74 (3H, s), 5.96 (1H, d,
J¼15.4 Hz), 6.23 (1H, d, J¼10.9 Hz), 7.25 (1H, dd, J¼15.4, 10.9 Hz),
7.25–7.38 (5H, m). MS m/z (%) 214 (Mþ, 100), 183 (25), 171 (43), 155
(70), 128 (61), 105 (49), 91 (12), 77 (49), 76 (10), 51 (19), 43 (14).
Calcd for C14H14O2: M, 214.0994. Found: m/z 214.0993.
4.1.30. 8-(Furan-2-yl-iodomethylene)-1,4-dioxaspiro[4.5]-
decane (19h)
Colorless oil; IR (neat) 2951, 2882, 1366, 1217, 1122, 1086, 1034,
907, 785, 739 cmꢀ1
;
1H NMR
d
1.64 (2H, t, J¼6.5 Hz), 1.79 (2H, t,
Acknowledgements
J¼6.5 Hz), 2.61 (2H, t, J¼6.5 Hz), 2.72 (2H, t, J¼6.5 Hz), 3.98 (4H, s),
6.32 (1H, dd, J¼3.3, 0.8 Hz), 6.38 (1H, dd, J¼3.3, 1.9 Hz), 7.41 (1H, dd,
J¼1.9, 0.8 Hz). MS m/z (%) 346 (Mþ, 25), 219 (100), 175 (13), 147 (10),
133 (27), 105 (12), 99 (12), 86 (12), 77 (8), 28 (20). Calcd for
C13H15O3I: M, 346.0066. Found: m/z 346.0067.
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, and TUS Grant for Research
Promotion from Tokyo University of Science, which are gratefully
acknowledged.
4.1.31. 2-(Cyclopentadecylidenemethyl)furan (20a)
Colorless oil; IR (neat) 2927, 2857, 1652, 1460, 1015, 726 cmꢀ1
;
References and notes
1H NMR
d
1.33–1.58 (24H, m), 2.15 (2H, t, J¼7.3 Hz), 2.38 (2H, t,
J¼7.7 Hz), 6.06 (1H, s), 6.16 (1H, d, J¼3.3 Hz), 6.37 (1H, dd, J¼3.3,
1.8 Hz), 7.33 (1H, d, J¼1.3 Hz). MS m/z (%) 288 (Mþ, 100), 135 (12),
121 (21), 94 (37), 81 (23), 79 (12), 55 (16), 41 (22), 28 (38). Calcd for
C20H32O: M, 288.2452. Found: m/z 288.2457.
1. Some monographs and reviews with regard to the chemistry of carbenes and
carbenoids: (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. Tetra-
hedron 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.
4.1.32. 2-(Cyclohexylidenemethyl)furan (20b)
Colorless oil; IR (neat) 2928, 2853, 1658, 1447, 1149, 1014, 926,
848, 727 cmꢀ1; 1H NMR
d 1.55–1.59 (6H, m), 2.21–2.29 (2H, m), 2.59
(2H, m), 5.96 (1H, s), 6.15 (1H, d, J¼3.4 Hz), 6.36 (1H, dd, J¼3.3,
1.5 Hz), 7.23 (1H, d, J¼1.5 Hz). MS m/z (%) 162 (Mþ, 76), 133 (12), 120
(13), 94 (100), 81 (43), 79 (26), 55 (15), 39 (23), 28 (72). Calcd for
C11H14O: M, 162.1044. Found: m/z 162.1040.
2. Doering, W. v. E.; Buttery, R. G.; Laughlin, R. G.; Chaudhuri, N. J. Am. Chem. Soc.
1956, 78, 3224.
4.1.33. 5-(1,4-Dioxaspiro[4.5]dec-8-ylidene)-penta-2,4-dienoic acid
methyl ester (24a)
3. (a) Satoh, T. Chem. Soc. Rev. 2007, 36, 1561; (b) Satoh, T. In The Chemistry of
Organomagnesium Compounds; Rappoport, Z., Marek, I., Eds.; John Wiley and
Sons: Chichester, UK, 2008; pp 717–769.
4. Satoh, T.; Sakamoto, T.; Watanabe, M.; Takano, K. Chem. Pharm. Bull. 2003, 51,
966.
5. Satoh, T.; Takano, K.; Ota, H.; Someya, H.; Matsuda, K.; Koyama, M. Tetrahedron
1998, 54, 5557.
6. Preliminary results of this study were reported as a letter: Satoh, T.; Mori, N.;
Obuchi, K. Tetrahedron Lett. 2007, 48, 6453.
7. (a) Satoh, T.; Kawashima, T.; Takahashi, S.; Sakai, K. Tetrahedron 2003, 59, 9599;
(b) Sugiyama, S.; Satoh, T. Tetrahedron: Asymmetry 2005, 16, 665.
8. Some papers for the alkenylation of thiophenes: (a) Li, Y.; Li, Z.; Li, F.; Wang, Q.;
Tao, F. Tetrahedron Lett. 2005, 46, 6159; (b) Wu, M.-Y.; Yang, F.-Y.; Cheng, C.-H.
J. Org. Chem. 1999, 64, 2471; (c) Zeni, G.; Alves, D.; Braga, A. L.; Stefani, H. A.;
Nogueira, C. W. Tetrahedron Lett. 2004, 45, 4823; (d) Tsukada, N.; Murata, K.;
Inoue, Y. Tetrahedron Lett. 2005, 46, 7515; (e) Hong, P.; Cho, B.-Re.; Yamazaki, H.
Chem. Lett. 1980, 507; (f) Maruyama, O.; Yoshidomi, M.; Fujiwara, Y.; Taniguchi,
H. Chem. Lett. 1979, 1229.
9. Watanabe, M.; Nakamura, M.; Satoh, T. Tetrahedron 2005, 61, 4409.
10. (a) Taschner, M. J.; Kraus, G. A. J. Org. Chem. 1978, 43, 4235; (b) Atsumi, K.;
Kuwajima, I. J. Am. Chem. Soc. 1979, 101, 2208; (c) Takanishi, K.; Urabe, H.;
Kuwajima, I. Tetrahedron Lett. 1987, 28, 2281.
Colorless crystals; mp 95–96 ꢁC (AcOEt–hexane); IR (KBr) 2956,
1947, 1709, 1633, 1429, 1306, 1259, 1187, 1163, 1122, 1067, 1030, 981,
897, 866 cmꢀ1; 1H NMR
d
1.77 (4H, t, J¼6.6 Hz), 2.30–2.39 (4H, m),
3.74 (3H, s), 3.97 (4H, s), 5.82 (1H, m), 5.85 (1H, dd, J¼15.6, 0.6 Hz),
7.18 (1H, dd, J¼15.6, 11.0 Hz); 13C NMR
d 206.48 (C, allene), 167.17
(CO), 143.56 (CH), 118.62 (CH), 107.87 (C), 101.86 (C), 91.29 (CH),
64.25 (2CH2), 51.36 (CH3), 35.04 (2CH2), 27.87 (2CH2). MS m/z (%)
250 (Mþ, 58), 219 (16), 205 (10), 191 (19),177 (13),163 (16), 147 (10),
124 (16), 119 (10), 99 (54), 86 (100), 77 (20), 55 (19), 42 (18). Anal.
Calcd for C14H18O4: C, 67.15; H, 7.19. Found: C, 67.18; H, 7.25.
4.1.34. 5-Cyclopentadecylidenepenta-2,4-dienoic acid methyl
ester (25a)
Colorless oil; IR (neat) 2929, 2857, 1941, 1721, 1627, 1459, 1440,
1301, 1260, 1171, 1113, 982, 868 cmꢀ1; 1H NMR
d 1.34–1.37 (20H, m),