Three types of products by carbon nucleophiles toward methoxyphenylacetylenic sulfones

Article abstract of DOI:10.1016/j.tet.2011.09.078

Methoxy-arylacetylenic sulfones were examined to react with various carbanion nucleophiles to result in the three types of products; thus, (i) nucleophiles (MeLi·LiBr, Vinyl MgBr, LiCH₂CN) showed the α-addition, however, (ii) Li-CC-TMS afforded β-addition (conjugate addition) products. The (iii) displacement reaction through α-addition/ isomerization/trans-elimination was enhanced by the presence of ortho-methoxy group at high temperature. The heteroatom nucleophiles (nitrogen, oxygen or sulfur atom) in a protic solvent provided only conjugate addition products as reported.

Full text of DOI:10.1016/j.tet.2011.09.078

Tetrahedron 67 (2011) 9957e9965
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Three types of products by carbon nucleophiles toward methoxyphenylacetylenic
sulfones
*
Chia-Yi Cheng, Minoru Isobe
Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 1 August 2011
Received in revised form 16 September 2011
Accepted 19 September 2011
Available online 24 September 2011
Methoxy-arylacetylenic sulfones were examined to react with various carbanion nucleophiles to result in
the three types of products; thus, (i) nucleophiles (MeLi$LiBr, Vinyl MgBr, LiCH2CN) showed the
dition, however, (ii) LieC^CeTMS afforded -addition (conjugate addition) products. The (iii) dis-
placement reaction through -addition/isomerization/trans-elimination was enhanced by the presence
a-ad-
b
a
of ortho-methoxy group at high temperature. The heteroatom nucleophiles (nitrogen, oxygen or sulfur
atom) in a protic solvent provided only conjugate addition products as reported.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Acetylenic sulfone
a
b
-Addition
-Addition
Displacement
Conjugate addition
Chelation effect
Isomerization
trans-Elimination
1. Introduction
controlling the reactivity of acetylenic sulfone 4 with the carbanion
nucleophiles during the course of solanoeclepin synthesis.6,7 But,
We have been studying on the vinylic sulfone system as 1 as one
of the key reactions for stereocontrolled CeC bond formation in the
total syntheses of various natural products, such as maytansine,1,2
okadaic acid,3 tautomycin,3,4 ciguatoxin,5 etc. When one uses
alkyllithium, alkenyllithium or alkynyllithium as NueLi in tetra-
hydrofuran (THF) solvent, extremely high stereoselectivity results
to afford syn products 2 due to chelation effects, which is called
heteroatom directed conjugate addition (HADCA)6,7 (Scheme 1).
HADCA can switch the selectivity to give anti product 3 under
stereoelectronic control in polar solvents.8e11 The selectivity is due
to the significant neighboring group effect by the oxygen atom.12e16
In cases without the oxygen atom presenting around the vinyl-
sulfone moiety, low reactivity is observed in a rate of slower than 1/
100 due to no chelation nor stereoelectronic effects.11 The function
of the oxygen atom is thus significant for reactivity and selectivity
in HADCA. On the other hand, further enhanced reactivity and se-
lectivity was observed under chelation control by adding NaBr in
case of lithium acetylides as nucleophile.6,7 The salt-effects sug-
gested that reactivity was very much depending upon the counter
cations of the carbon nucleophiles. We became interested in
alkylacetylenic sulfones are easy to equilibrate to the correspond-
ing allenic or propargylic sulfones, so that it is too complex to un-
derstand the mechanism of alkynylsulfone moiety with
alkyllithium or Grignard reagent. Extensive studies have been ac-
cumulated in a review article.17 In this paper, we focused on the
reactivity of acetylenic sulfone 4a,b with special reference to the
roles of the oxygen atom (Scheme 1).
2. Results of carbon nucleophiles to acetylenic sulfones
An acetylenic sulfone with an alkyl substituent in general, e.g.
PhSO2C^CeCH3, was reported undergoing rapid equilibration to
the corresponding allenic sulfone PhSO2eCX¼C]CH2 with
various metal complexes showing very different reactivity18,19 (for
details see reviews17). Here we studied alternative system
having the aromatic substituents to the acetylenic sulfones; thus,
PhSO2C^CeAr 4, to avoid such equilibria. The acetylenic sulfones
4a and 4b were synthesized from commercially available
1-bromo-2-methoxybenzene 9 and 1-bromo-4-methoxybenzene
10 under (a) Sonogashira cross-coupling,20,21 (b) retro-Favorskii
reaction,22 (c) lithium acetylide with S-phenyl benzenesulfono-
thioate, and (d) oxidized with m-CPBA to obtain 39% and 47% yield
in four steps, respectively (Scheme 2). To investigate the chelation
* Corresponding author. E-mail address: minoru@mx.nthu.edu.tw (M. Isobe).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.09.078

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C.-Y. Cheng, M. Isobe / Tetrahedron 67 (2011) 9957e9965
chelation product
stereoelectronic product
H
Nu
Nu
Nu-Li
THF
SiMe3
SO2Ph
or
SO2Ph
R1
R1
R1
O
O
O
SO2Ph
R
R
R
3
1
2
alpha-C addition
displacement
beta-C addition
α
C
SO2Ph
R,Li
H
R
R
β
C
SO2Ph
SO2Ph
SO2Ph
R-Li
or
R2
Li,R
R1
R
H
THF
R2
R1
R2
R2
R1
R2
R1
R1
5
7
6
8
4
a R1= OMe, R2= H
b R1= H, R2= OMe
c R1= R2 = H
Scheme 1. Reactivity types for vinylic sulfone and arylacetylenic sulfone.
sulfone moiety (Scheme 1). The plan was first to add lithium
carbanions to 4a,b, and to see the difference in the oxygen-effects
to afford the three types of the products 6e8. But the product 7
was often found with amazing different selectivity from our ex-
pectation. The results are summarized in Table 1 with several
nucleophiles.
A solution of ortho-methoxyphenylacetylenic sulfone 4a in THF
solvent was added 1.5 equiv of MeLi$LiBr at 0 ꢀC to afford dis-
placement product 11 in 45% yield, together with recovery of 44%
4a (entry 1). Addition of 1.5 equiv MeLi$LiBr into 4a at ꢁ78 ꢀC
afforded a displacement product 11 in 61% yield (entry 3).
In case of para-methoxyphenylacetylenic sulfone 4b, we ob-
tained similar displacement product 12 in 60% yield at 0 ꢀC (entry 2)
or in 63% by excess amount 5 equiv of MeLi$LiBr at ꢁ78 ꢀC (entry 5).
Amazingly, the product obtained from 4b with 1.5 equiv MeLi$LiBr
R3
Br
(a)
(b)
(c)
(d)
R2
R1
R2
R1
9
: R1 = OMe, R2 = H
10 : R1 = H, R2 = OMe
4a : R1 = OMe, R2 = H,
R3 = SO2Ph, 39% (4 steps)
4b : R1 = H, R2 = OMe
R3 = SO2Ph, 47% (4 steps)
Scheme 2. Preparation of arylacetylenic sulfones 4a and 4b. Reagent and condition:
(a) 2-methylbut-3-yn-2-ol, Pd(PPh3)2Cl2, CuI, PPh3, Et3N, reflux, 5 h. (b) KOH, toluene,
reflux, 1.5 h. (c) n-BuLi, PhSO2eSPh, THF, ꢁ78 ꢀC, 5 h. (d) m-CPBA, DCM, 0 ꢀC, 2 h.
effects, a methoxy group was placed at the ortho-position 4a and
also para-position 4b for comparison onto this aromatic ring,
which would keep the same electronic situation to the acetylenic
Table 1
Products by carbon nucleophiles to the acetylenic sulfones 4a and 4b
Entrya
Substrate
Nucleophile (equiv)
Temp (ꢀC)
Time (h)
R
Products
Yieldb (%)
A
B
C
1c
2
3
4
5
4a
4b
4a
4b
4b
MeLi$LiBr (1.5)
MeLi$LiBr (1.5)
MeLi$LiBr (1.5)
MeLi$LiBr (1.5)
MeLi$LiBr (5.0)
0
0
ꢁ78
ꢁ78
ꢁ78
1
1
1
1
1
Me
Me
Me
Me
Me
d
d
d
d
d
d
11
12
11
d
45d
60
61
25
63
d
d
15b
d
12
6
4a
4b
4a
4b
4a
ꢁ40
ꢁ40
ꢁ78
ꢁ78
ꢁ78
4.5
4.5
4.5
4.5
4.5
d
d
d
d
d
d
17
d
d
d
d
40
7
19
18
19
18
80
8
30e
18f
60g
9
10
11
12
4b
4a
ꢁ78
ꢁ78
4.5
19
20
d
d
d
d
25f
37i
LiCH2CNh (3.0)
0.25
eCH2CN

C.-Y. Cheng, M. Isobe / Tetrahedron 67 (2011) 9957e9965
9959
Table 1 (continued )
Entrya
Substrate
Nucleophile (equiv)
Temp (ꢀC)
Time (h)
R
Products
Yieldb (%)
A
B
C
13
14
15
4b
4a
4b
LiCH2CNh (3.0)
LiCH2CNh (9.0)
LiCH2CNh (9.0)
ꢁ78
ꢁ78
ꢁ78
0.25
0.1
0.1
eCH2CN
eCH2CN
eCH2CN
21
20
21
d
d
d
d
d
d
21j
40
27
k
16
4a
4b
(10.0)
ꢁ40
5
d
d
22
23
24
25þ44l
ꢁ78
ꢁ40
2
3
k
17
(10.0)
d
50
a
Every reaction is 100 mg scale.
Isolated yield.
b
c
d
e
f
The solution of 4a in THF was added into MeLi$LiBr in THF solution.
The 4a was recovered in 44% yield.
The 4a was recovered in 43% yield.
The conversion yield was determined by 1H NMR.
The 4a was recovered in 18% yield.
g
h
i
Acetonitrile was deprotonated with n-BuLi at 0 ꢀC for 1 h.
High polar byproduct (42 mg) was obtained.
j
High polar byproduct (65 mg) was obtained.
k
l
Trimethylsilylacetylene was deprotonated with MeLi$LiBr at 0 ꢀC for 1 h.
The yield of displacement products
X (X¼H, TMS, combined yield).
at ꢁ78 ꢀC in 25% was 15b (entry 4), which showed different NMR
from those of reported data for 12,23,24 13,14 nor 16. Particularly the
ꢁ78 ꢀC gave 18 in 30% yield with 43% recovery of 4a (entry 8), so
increasing the nucleophile to 10 equiv increased the yield of 18e60%
(entry 10). On the other hand, addition of vinylmagnessium bromide
to 4b gave 19 in 80% yield at ꢁ40 ꢀC (entry 7). But the same reaction
at lower temperature (ꢁ78 ꢀC) or larger excess (10 equiv) afforded
lower yields (entry 9 and 11). Both of the additionproducts 18 and 19
became crystalline, so the structures were determined by X-ray
crystallographic analysis to result in the structure as shown in Fig. 2.
vinylic proton of 15b appeared at around
reported data of 1325 is
6.58 ppm. The structure of this adduct
15b26 was proven from the NMR data (HMBC and NOESY spectra) as
d 7.75 ppm, while the
d
shown in Fig. 1. So 15b is a anti-addition at the a-carbon but not
a syn-addition as 16.27 These authentic data25e27 were taken from
the compounds prepared by completely different way. The chem-
ical shift data are summarized in Table 2.
The addition took place at the a-carbon in anti mode in these cases.
CH3
CH3
CH3
SO2Ph
MeO
H
H
SO2Ph
R2
R1
MeO
13
14
11 R1= OMe, R2= H
12 R1= H, R2= OMe
H
C
H
H
H
OMe H
SO2Ph
SO2Ph
CH3
CH3
HMBC
SO2Ph
CH3
MeO
MeO
15a
16
15b
NOESY
Fig. 1. Products of MeLi$LiBr addition to 4a and 4b.
Table 2
Fig. 2. Products of vinylmagnesium bromide to 4a and 4b.
Chemical shifts of vinylic proton
H
R
OMe H
OMe R
SO Ph
SO Ph
SO Ph
2
2
SO Ph
2
2
Acetonitrile anion was generated with n-butyllithium and then
added to 4a and 4b, respectively. In these cases (entries 12e15), the
R
R
H
R
H
MeO
MeO
δ ppm
δ ppm
δ ppm
δ ppm
a-addition products 20 and 21 were isolated. The yields were
21e40% with some polar side products. These structures were
confirmed by NMR with HMBC (Fig. 3). None of the conjugate ad-
dition product nor displacement product was observed under the
conditions shown in Table 1.
eCH3
(7.74)a 7.75
7.81c
7.99
6.58b
eCH]CH2 8.15a
eCH2CN
eC^CeH
8.19
7.54
7.04
Trimethylsilyl acetylene was lithiated by MeLi$LiBr and then
added to 4a and 4b, respectively. We obtained the conjugate ad-
dition products 22 and 23 in relatively moderate yields. The case of
4a we obtained the displacement product 24 only on the ortho-
methoxy case. The ratios of addition product 22 and displacement
product 24 were isolated in a ratio of 1:2 in 69% total yield. The
HMBC experiments of 22 and 23 showed that the addition products
took place at the b-carbon, thus conjugate addition (Fig. 3).
Structure assignments of the products by the carbon nucleo-
philes were performed from NMR and X-ray crystallographic
a
Taken from Ref. 26.
Taken from Ref. 25.
Structures confirmed by X-ray crystallographic analysis.
b
c
Next, we employed vinylmagnessium bromide as the second
nucleophile (Table 1, entries 6e11). Its reactivity was relatively lower
than MeLi$LiBr,6,7 so large excess reagents were used in 5e10 equiv
to the acetylenic sulfones 4a and 4b to complete the reaction. Ad-
dition of vinylmagnessium bromide(5 equiv) to 4a at ꢁ40 ꢀC for 4.5 h
afforded the displacement product 17 (entry 6). The same reaction at

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C.-Y. Cheng, M. Isobe / Tetrahedron 67 (2011) 9957e9965
addition at the
addition of sulfide took place similarly at the
b
-carbon of the acetylenic sulfones 4a and 4b. The
-carbon to provide
H
C
b
MeO
C
H
C
H
C
H
C
OMe
C
28a, 28b. The sodium methoxy addition product was converted to
the keto-sulfones 29b only on para-methoxy case. The case of 4a, we
obtained stereoisomer mixture addition products. The conjugate
adduct 27b became crystalline, and the structure was determined by
X-ray crystallographic analyzed as shown in Fig. 5.
SO2Ph
CN
SO2Ph
CN
SO2
H
H
MeO
H
H
20
21
22
H
4. Discussions
R3
H
The three carbon nucleophiles toward arylacetylenic sulfones
C
SO2
4a, 4b showed either
a
-addition in anti-manner or displacement,
-addition product was obtained (Table
C
but no -syn-addition nor
a
b
HMBC
H
MeO
R2
R1
1, entries 1e15). The displacement products 11 and 12 with
MeLi$LiBr (Table 1, entries 2 and 3) were obtained in a tendency of
conditions (1) at relatively higher temperature (0 ꢀC), (2) in larger
excess amounts (5 equiv) and/or with substrates (3) the ortho-
methoxy compound 4a rather than para-methoxy 4b. A anti-adduct
15b was isolated from 4b but not corresponding adduct 15a from
24 R1= OMe, R2= H, R3= H
23
24a R1= OMe, R2= H, R3= TMS
25 R1= H, R2= OMe
Fig. 3. Products of acetonitrile and acetylide anions to 4a and 4b.
the ortho-methoxy precursor 4a. These results suggest that the a-
analysis. In addition to confirming these structures, the vinylic
protons of the - or -positions are summarized in Table 2.
Chemical shifts of the -H to the vinylsulfones appear between
7.75 and 8.19 ppm, while those of the -H are located between
6.58 and 7.54 ppm. Namely the lower chemical shifts than
7.75 ppm can be assigned as the -proton, thus -addition.
addition D of methyllithium to 4a first gives the anionic in-
termediate E, lithium cation of which would chelate with the ortho-
methoxy oxygen atom. Under the conditions, E-isomer might
isomerize to Z-isomer at this sp2 carbanion atom to F, which could
kick out the phenylsulfonyl group by trans-elimination to provide
G, ending up with the formation of formal displacement product.
a
b
b
d
d
d
a
b
a
This a-addition, however, takes place without the ortho-methoxyl
group under more drastic conditions (longer reaction time or larger
3. Results of heteroatom nucleophiles to 4a and 4b
amount of nucleophiles). Therefore, ortho-methoxyl group is not
essential to a-addition but enhancing the isomerization reaction
After we examined the four kinds of carbon nucleophiles to the
arylacetylenic sulfones, we performed the addition by heteroatom
nucleophiles, such as nitrogen, sulfide, and oxygen as shown in
Fig. 4. In fact, various nucleophiles were added to arylacetylenic
sulfones in ethanol or methanol solvent at 0 ꢀC to room tempera-
ture to afford selectively the addition products. All of them are
leading to the trans-elimination ending up with the displacement.
Russel has proposed a radical mechanism under photochemical
reaction condition of arylacetylenic sulfonyl compounds.29,30 Fuchs
suggested similar radical mechanism with acetylenic triflones.31
In the current cases, an ionic mechanism is proposed to include
a-addition/isomerization/trans-elimination mechanism for this
conjugate addition to the b-carbon of the acetylenic sulfones in
displacement reaction as shown in Fig. 6. This is also supported by
the fact in the vinylmagnessium bromide case (Table 1, entry 6) that
the displacement product 17 was obtained at ꢁ40 ꢀC but never
high yields (70e88% yields) as summarized in Table 3. Judging from
the higher yields with these heteroatom nucleophiles, neither
displacement nor very little addition took place at the a-carbon of
the acetylenic sulfones 4a and 4b.
observed at ꢁ78 ꢀC, and that only
a-anti-addition products 18 and
19 were obtained at that lower temperature conditions. In the
meantime, we utilized 5 equiv vinylmagnessium bromide to react
with phenylethynyl-sulfonyl benzene 4c at ꢁ40 or ꢁ78 ꢀC for 4.5 h,
SO2Ph
Nu-H
and that only a-addition product 32 was gained but no displace-
ment product. The product I was proposed the
a-addition in-
EtOH or MeOH
R2
R1
termediate H through -attack to 4c, but no isomerization/
a
NuH= iPrNH2/EtOH
C6H11NH2/EtOH
C6H5SH/MeOH
MeONa/MeOH
4a, 4b
elimination, as shown in Fig. 6 and Scheme 3.
A clear syn-addition of lithium dimethylcuprate to phenyl tri-
methylsilylethynyl sulfone afforded the conjugate adduct, showing
a R1= OMe, R2= H
b R1= H, R2= OMe
the vinylic H at
d 6.25 ppm. Addition of phenyllithium afforded
benzenesulfenic acid in >70% yields meaning displacement re-
action, but the product was detected by gas chromatography.32
An alternative carbon nucleophile was examined for a conjugate
addition to the acetylenic sulfone 33. The corresponding methyl-
ketone of 33 afforded under basic conditions largely a mixture of
the dimeric products 35 instead of the pentanone 34. So treatment
of 33 under acidic conditions, such as p-toluenesulfonic acid
monohydrate afforded a cyclopentanone product 34 in 25% isolated
yield together with 35 in 35% yield, which should proceed via the
Nu
O
SO2Ph
SO2Ph
H
R2
R1
R2
R1
29b
26a, 26b, Nu= -NH(i-Pr)
27a, 27b, Nu= -NHC6H11
28a, 28b, Nu= -SC6H5
Fig. 4. Heteroatom nucleophiles addition in ethanol and methanol to 4a and 4b.
intramolecular b-attack as shown by 33a (Fig. 7).
Heteroatom nucleophiles have already been reported in terminal
acetylenic sulfone (HeC^CeSO2Ar) or alkylacetylenic sulfones to
results in the conjugate addition.17,19,28 The arylacetylenic sulfones
show similar but simple conjugate addition with Z-isomers. The
enamines 26a, 26b and 27a, 27b were isolated only in anti-selective
5. Conclusion
Addition reaction to acetylenic sulfones was studied to give
three types of products: (i) -addition products by those high pKa
carbon nucleophiles, such as MeLi$LiBr, vinyl MgBr and LiCH2CN
a

C.-Y. Cheng, M. Isobe / Tetrahedron 67 (2011) 9957e9965
9961
Table 3
Heteroatom nucleophiles to the arylacetylenic sulfones 4a and 4b
SO2Ph
R
Heteroatom
Nucleophile
SO2Ph
solvent ( 0.02 M )
Temp. Time.
H
R2
R1
R2
R1
a : R1 = OMe, R2 = H
b : R1 = H, R2 = OMe
4a : R1 = OMe, R2 = H
4b : R1 = H, R2 = OMe
Entrya
1b
Substrate
Nucleophile (equiv)
NH2
30 (6)
Temp (ꢀC)
Time (h)
Solvent
EtOH
R
Result (yield %)
4a
0 to rt (25)
4
26a (88%)
-NH
2b
3b
4b
4a
30 (6)
NH2
0 to rt (25)
0 to rt (25)
4
4
EtOH
EtOH
26b (75%)
27a (81%)
-NH
-NH
31 (6)
31 (6)
4b
4b
0 to rt (25)
4
EtOH
27b (70%)
-NH
5
6
4a
4b
NaBH4 (6)
PhSeSPh (6)
NaBH4 (6)
0
0
1
1
MeOH
MeOH
eSPh
eSPh
28a (82%)
28b (75%)
PhSeSPh (6)
O
H
SO2Ph
7
4b
NaOMe (3)
Reflux
1
MeOH
29b (72%)
MeO
a
Every reaction is 100 mg scale.
The solution of sulfones was added into the amine in EtOH solution at 0 ꢀC.
b
Heteroatom
Nucleophile
alpha addition
MeO
Li
Nu
OMe
SO2Ph
SO2Ph
SO2Ph
Nu
Li
Nu
H
R2
R1
Nu-H
D
E
5
OMe
Nu
isomerization MeO
trans elimination
SO2Ph
Li
Nu
F
G
MgBr
SO2Ph
H
SO2Ph
SO2Ph
alpha addition
slow
Nu
Fig. 5. HMBC and X-ray structure of 27b.
Nu
H
I
4c
(pKa ꢂ25); (ii)
b
-addition products by LieC^CeTMS (pKa z25);
-addition/isomeri-
Fig. 6. Possible mechanism of the displacement products through
a-addition.
and (iii) the displacement products through
a
zation/trans-elimination. This isomerization was enhanced by the
presence of ortho-methoxy group to afford displacement products,
although it happened even without o-OMe under more drastic
conditions using larger amount of nucleophiles or higher temper-
is striking contrast with the fact that lithium acetylide addition
took place at the -carbon, thus conjugate addition. It seems that
lithium acetylide is the border of - or -carbon attacking. Recently,
Xie and co-workers reported conjugate addition of alkyl- or aryl-
b
atures. The sulfonyl group made the
a-carbon itself electrophilic
a
b
due to its strongly electron withdrawing nature in THF solvent. This

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C.-Y. Cheng, M. Isobe / Tetrahedron 67 (2011) 9957e9965
Reactions were monitored by thin-layer chromatography carried
5.0 equiv.
MgBr
δ 7.88 ppm
SO2Ph
H
H
SO2Ph
out on 0.25 mm Silica Gel 60 F254 coated glass plates (Merck, Art
1.05715) using UV light as visualizing agent Ammonium molybdate
tetrahydrate solution and heated as developing agents. GeduranÒ
THF
H
Silica Gel 60 (particle size 40e63
mm, purchased from E-Merck
H
32
Chemicals, Inc.) was used for flash column chromatography.
4c
Condition a: -40 oC, 4.5 h, 50%
Condition b: -78 oC, 4.5 h, 81%
6.1.1. 1-(2(2-Methoxyphenyl)ethynylsulfonyl)benzene
(4a)36. As
light yellow solid, Rf 0.28 (ethyl acetate/hexane¼1:5). Mp
Scheme 3. Anti-Addition of vinylmagnesium bromide to phenylethynyl-sulfonyl ben-
zene 4c.
81.1e81.9 ꢀC; 1H NMR (400 MHz; CDCl3):
d 3.79 (s, 3H), 6.83e6.90
(m, 2H), 7.37e7.40 (m, 2H), 7.55 (t, J¼7.6 Hz, 2H), 7.62e7.65 (m, 1H),
8.04e8.06 (m, 2H); 13C NMR (100 MHz, CDCl3):
d
55.7, 88.6, 91.6,
106.9, 110.9, 120.4, 127.1, 129.2, 133.3, 133.9, 134.3, 142.0, 161.6;
HRMS (EI) calcd for C15H12O3S (Mþ) m/z 272.0507; found 272.0502.
α
C
SO2Ph
SO2Ph
β
C
C
C
6.1.2. 1-(2-(4-Methoxyphenyl)ethynylsulfonyl)benzene (4b)37,38. As
light yellow solid, Rf 0.25 (ethyl acetate/hexane¼1:3). Mp
TsOH
CH3
O
CH2
OR
33a
CH(OMe)3
MeOH
74.7e75.2 ꢀC; 1H NMR (400 MHz; CDCl3):
d 3.81 (s, 3H), 6.85 (d,
O
J¼8.4 Hz, 2H), 7.45 (d, J¼8.8 Hz, 2H), 7.57 (t, J¼7.6 Hz, 2H), 7.65 (t,
J¼7.2 Hz, 1H), 8.05 (d, J¼7.6 Hz, 2H); 13C NMR (100 MHz, CDCl3):
33
d
55.4, 84.5, 94.7, 109.4, 114.4, 127.2, 129.3, 133.9, 134.7, 142.0, 162.1;
HRMS (EI) calcd for C15H12O3S (Mþ) m/z 272.0507; found 272.0510.
H
H
SO2Ph
H
SO2Ph
+
SO2Ph
6.2. The general procedure for carbon nucleophile to the
acetylenic sulfones 4a and 4b (Table 1, entries 2e11)
The acetylenic aulfones 4a (or 4b) was dissolved in dry THF
(0.02 M), then the carbon nucleophile (MeLi$LiBr or vinyl-
magnessium bromide) was dropwise added into the mixture at the
reaction temperature as shown in Table 1. After the reaction com-
pleted, the reaction mixture was poured into ice-cold saturated
aqueous NH4Cl, extracted with ethyl acetate (20 mLꢃ3). The com-
bined organic layers were washed with brine, dried over MgSO4,
and concentrated. The residue was purified by chromatography on
silica gel with ethyl acetate and hexane.
O
O
35
34
Fig. 7. Intramolecular nucleophile to form cyclopentanone by conjugate addition.
zinc halides to the acetylenic sulfones under toluene-refluxing
condition in the presence of CuI to afford syn-addition prod-
ucts.33,34 The alkynyl nucleophiles, however, cannot undergo the
cuprate mediated conjugate addition due to greater s-character for
the transformation to the electrophile.35 Therefore, the conjugate
addition of acetylide is a quite unique example. The finding of the
6.2.1. 1-Methoxy-2-(prop-1-ynyl)benzene (11). As yellow liquid, Rf
0.80 (ethyl acetate/hexane¼1:5). 1H NMR (400 MHz; CDCl3):
d 2.10
addition product at the a-carbon in this study is also remarkable.
(s, 3H), 3.86 (s, 3H), 6.83e6.88 (m, 2H), 7.21 (d, J¼8.0 Hz,1H),7.35 (d,
J¼7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 4.7, 55.7, 75.7, 89.9,
110.4, 113.0, 120.3, 128.8, 133.5, 159.7; HRMS (EI) calcd for C10H10
Further studies on addition reaction to acetylenic sulfones with
carbon nucleophiles having other counter metal ions are now in
progress, which would be disclosed elsewhere.
O
(Mþ) m/z 146.0732; found 146.0737.
6. Experimentals
6.2.2. 1-Methoxy-4-(prop-1-ynyl)benzene (12). As yellow liquid, Rf
0.70 (ethyl acetate/hexane¼1:5). 1H NMR (400 MHz; CDCl3):
d 2.01
6.1. General information
(s, 3H), 3.77 (s, 3H), 6.79 (d, J¼8.0 Hz, 2H), 7.31 (d, J¼8.0 Hz, 2H); 13C
NMR (100 MHz, CDCl3):
d 4.2, 55.2, 79.4, 84.0, 113.8, 116.1, 132.7,
Proton nuclear magnetic resonance (1H NMR) spectra were
recorded on a BRUKER AV-400 (400 MHz) or a BRUKER DMX-600
(600 MHz). Data were reported as follows; chemical shift as
158.9; HRMS (EI) calcd for C10H10O (Mþ) m/z 146.0732; found
146.0729.
d
values referenced to CHCl3 (7.24), integration, multiplicity
6.2.3. 1-((E)-1-(4-Methoxyphenyl)prop-1-en-2-ylsulfonyl)benzene
(s¼singlet, d¼doublet, t¼triplet, q¼quartet, br¼broadened,
m¼multiplet), coupling constants in Hz, and assignment. Carbon
nuclear magnetic resonance (13C NMR) spectra were recorded on
a BRUKER AV-400 (100 MHz) or a BRUKER DMX-600 (150 MHz).
(15b)*. As colorless liquid, Rf 0.23 (ethyl acetate/hexane¼1:5). 1H
NMR (400 MHz; CDCl3):
d
2.10 (s, 3H), 3.81 (s, 3H), 6.91 (d, J¼8.4 Hz,
2H), 7.37 (d, J¼8.4 Hz, 2H), 7.51 (t, J¼7.2 Hz, 2H), 7.58 (t, J¼7.2 Hz,
1H), 7.75 (s, 1H), 7.89 (d, J¼7.2 Hz, 2H); 13C NMR (100 MHz, CDCl3):
Chemical shifts are reported in
d
values and referenced to CHCl3
d 13.3, 55.3, 114.1, 126.2, 128.0, 129.1, 131.5, 133.1, 134.4, 137.2, 139.4,
(77.00). High resolution mass spectra (HRMS) were recorded on
FINNIGAN MAT-95XL Mass spectrometers in m/z respectively in
NSC Instrumentation Center at NTHU or a Bruker APEX II ESI/FT-MS
Mass spectrometers in m/z respectively in NSC Instrumentation
Center at NSYSU. Melting points were obtained with a SMP3
melting point apparatus. X-ray diffraction spectra were recorded on
Siemens Smart CCD in NSC Instrumentation Center at NTHU. In-
frared (IR) spectrum was recorded on a HORIBA FT-IR spectrometer
using KBr salt plates, and reported in terms of wavenumber (cmꢁ1).
160.5; HRMS (EI) calcd for C16H16O3S (Mþ) m/z 288.0820; found
288.0826. *Compound 15b was reported by different synthetic
route.29
6.2.4. 1-(But-3-en-1-ynyl)-2-methoxybenzene (17). As brown liq-
uid, Rf 0.55 (ethyl acetate/hexane¼1:5). 1H NMR (400 MHz; CDCl3):
d
3.87 (s, 3H), 5.51 (d, J¼11.2 Hz, 1H), 5.73 (d, J¼17.6 Hz, 1H), 6.06
(dd, J¼11.2, 17.6 Hz, 1H), 6.84e6.91 (m, 2H), 7.27 (t, J¼8.0 Hz, 1H),
7.40 (d, J¼7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 55.8, 86.2, 92.1,

C.-Y. Cheng, M. Isobe / Tetrahedron 67 (2011) 9957e9965
9963
110.6, 112.3, 117.4, 120.4, 126.6, 129.8, 133.6, 159.8; HRMS (EI) calcd
6.95 (t, J¼7.6 Hz, 1H), 7.31e7.35 (m, 1H), 7.51 (d, J¼7.6 Hz, 2H), 7.54
(s, 1H), 7.60 (d, J¼6.8 Hz, 1H), 7.64 (d, J¼8.0 Hz, 1H), 8.04 (d,
for C11H10O (Mþ) m/z 158.0732; found 158.0726.
J¼7.6 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 55.7, 78.2, 92.0, 111.6,
6.2.5. 1-((E)-1-(2-Methoxyphenyl)buta-1,3-dien-2- ylsulfonyl) ben-
120.7, 123.7,128.0, 128.8, 131.2,131.3, 131.6, 133.3,138.6, 141.4, 157.4;
zene (18). As white solid, mp 108.6e109.1 ꢀC, Rf 0.28 (ethyl acetate/
HRMS (EI) calcd for C17H14O3S (Mþ) m/z 298.0664; found 298.0663.
hexane¼1:5). 1H NMR (400 MHz; CDCl3):
d 3.87 (s, 3H), 5.36 (d,
J¼11.6 Hz, 1H), 5.91 (d, J¼18.0 Hz, 1H), 6.33 (dd, J¼11.6, 18.0 Hz, 1H),
6.90e6.93 (m, 2H), 7.34 (t, J¼8.0 Hz, 1H), 7.39 (d, J¼7.2 Hz, 1H), 7.49
(t, J¼7.6 Hz, 2H), 7.56 (t, J¼7.2 Hz, 1H), 7.89 (d, J¼8.0 Hz, 2H), 8.15 (s,
6.2.10. 1-(Buta-1,3-diynyl)-2-methoxybenzene (24)39. As brown
liquid, Rf 0.63 (ethyl acetate/hexane¼1:3). 1H NMR (400 MHz;
CDCl3): d 2.51 (s, 1H), 3.87 (s, 3H), 6.85e6.90 (m, 2H), 7.30e7.34 (m,
1H); 13C NMR (100 MHz, CDCl3):
d
55.6, 110.8, 120.1, 122.2, 122.7,
1H), 7.45 (dd, J¼1.6, 7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 55.8,
126.6, 128.0, 128.8, 130.8, 131.5, 132.9, 135.3, 137.3, 140.2, 158.3;
68.4, 71.8, 72.0, 77.2,110.3,110.7,120.5,131.0,134.7,161.8; HRMS (EI)
HRMS (EI) calcd for C17H16O3S (Mþ) m/z 300.0820; found 300.0826.
calcd for C11H8O (Mþ) m/z 156.0575; found 156.0570.
6.2.6. 1-((E)-1-(4-Methoxyphenyl)buta-1,3-dien-2- ylsulfonyl) ben-
6.2.11. 1-((E)-1-(4-Methoxyphenyl)but-1-en-3-yn-2-ylsulfonyl) ben-
zene (19). As yellow solid, mp 120.7e122.2 ꢀC, Rf 0.20 (ethyl ace-
zene (23). As yellow liquid, Rf 0.15 (ethyl acetate/hexane¼1:5). 1H
tate/hexane¼1:5). 1H NMR (400 MHz; CDCl3):
d
3.81 (s, 3H), 5.43 (d,
NMR (400 MHz; CDCl3):
d
3.80 (s, 3H), 3.89 (s,1H), 6.86 (d, J¼8.8 Hz,
J¼11.6 Hz, 1H), 5.86 (d, J¼18.0 Hz, 1H), 6.35 (dd, J¼11.6, 18.0 Hz, 1H),
6.89 (d, J¼8.0 Hz, 2H), 7.47e7.49 (m, 4H), 7.54e7.57 (m, 1H), 7.81 (s,
2H), 7.04 (s, 1H), 7.50e7.54 (m, 2H), 7.58e7.62 (m, 3H), 8.03 (d,
J¼8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 55.4, 77.4, 93.5, 114.2,
1H), 7.86 (d, J¼8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d
55.4, 114.1,
127.0, 128.0, 128.8, 129.0, 132.3, 133.4, 134.3, 141.3, 162.0; HRMS (EI)
123.4, 125.8, 126.7, 128.0, 128.8, 132.4, 133.0, 135.5, 138.3, 140.1,
161.1; HRMS (EI) calcd for C17H16O3S (Mþ) m/z 300.0820; found
300.0815.
calcd for C17H14O3S (Mþ) m/z 298.0664; found 298.0672.
6.2.12. N-((Z)-1-(2-Methoxyphenyl)-2-(phenylsulfonyl)vinyl)
propan-2-amine (26a). To a solution of 4a (100 mg, 0.37 mmol) in
EtOH (13 mL) was dropwise added into the solution of isopropyl-
amine (0.19 mL, 2.20 mmol) in EtOH (5.5 mL, 0.4 M) at 0 ꢀC. The
stirring was allowed to warm to room temperature and continued
for 4 h. The mixture was poured into ice-cold aqueous HCl (pH¼4)
and extracted with ethyl acetate (20 mLꢃ3). The combined organic
layers were washed with saturated aqueous NaHCO3, followed by
brine, dried over MgSO4, and concentrated. The resides was puri-
fied by chromatography on silica gel with ethyl acetate and hexane
(1:3) as an eluent to afford 26a (107 mg, 88%) as yellow syrup, Rf
0.30 (ethyl acetate/hexane¼1:3). 1H NMR (600 MHz; CDCl3, 263 K):
6.2.7. (E)-4-(2-Methoxyphenyl)-3-(phenylsulfonyl)but-3-enenitrile
(20). Acetonitrile anion was generated from acetonitrile (58 mmL,
1.10 mmol) with n-butyllithium (2.5 M in hexane solution, 0.44 mL,
1.10 mmol) in dry THF (2.8 mL, 0.4 M) at 0 ꢀC for 1 h, then added
into the solution of 4a (100 mg, 0.37 mmol) in dry THF (16 mL) at
ꢁ78 ꢀC dropwise. After 15 min, the reaction mixture was poured
into ice-cold saturated NH4Cl, extracted with ethyl acetate
(20 mLꢃ3). The combined organic layers were washed with brine,
dried over MgSO4 and concentrated. The residue was purified by
chromatography on silica gel with ethyl acetate and hexane (1:5) as
an eluent to afford 20 (43 mg, 37%) as yellow solid. mp
100.7e101.7 ꢀC, Rf 0.25 (ethyl acetate/hexane¼1:3). 1H NMR
d
0.92 (d, J¼6.6 Hz, 3H)*, 1.07 (d, J¼6.0 Hz, 3H)*, 3.08e3.13 (m, 1H),
3.71 (s, 3H), 4.41 (s, 1H), 6.82 (d, J¼8.4 Hz, 1H), 6.86 (t, J¼7.2 Hz, 1H),
7.05 (d, J¼7.2 Hz, 1H), 7.27e7.31 (m, 2H), 7.41e7.44 (m, 2H),
7.46e7.48 (m, 1H), 7.88 (d, J¼8.4 Hz, 2H); 13C NMR (150 MHz, CDCl3,
(600 MHz; CDCl3):
d
3.46 (s, 2H), 3.85 (s, 3H), 6.95 (d, J¼8.4 Hz, 1H),
7.00 (t, J¼7.2 Hz, 1H), 7.27 (d, J¼7.8 Hz, 1H), 7.41 (t, J¼7.8 Hz, 1H),
7.58 (t, J¼7.2 Hz, 2H), 7.64e7.67 (m, 1H), 7.96 (d, J¼8.4 Hz, 2H), 8.19
263 K):
d 23.3*, 24.5*, 46.2, 55.2, 87.6, 110.4, 120.3, 123.9, 125.4,
(s, 1H); 13C NMR (150 MHz, CDCl3):
d
16.7, 55.5, 111.2, 115.3, 120.76,
128.6, 129.2, 130.7, 131.8, 144.9, 155.6, 156.7; HRMS (EI) calcd for
120.82, 128.3, 129.5, 129.6, 131.0, 132.3, 134.0, 138.7, 139.7, 157.6;
HRMS (EI) calcd for C17H15NO3S (Mþ) m/z 313.0773; found
313.0775.
C18H21NO3S (Mþ) m/z 331.1242; found 331.1240.
1
*The measurement of H and 13C NMR at 300 K afforded single
broad signal of isopropyl methyl group, therefore, the data are
measured at 263 ꢀK.
6.2.8. (E)-4-(4-Methoxyphenyl)-3-(phenylsulfonyl)but-3-enenitrile
(21). As yellow solid, mp 99.3e100.4 ꢀC, Rf 0.23 (ethyl acetate/
6.2.13. N-((Z)-1-(4-Methoxyphenyl)-2-(phenylsulfonyl)vinyl)
propan-2-amine (26b). As yellow syrup, Rf 0.35 (ethyl acetate/
hexane¼1:3). 1H NMR (400 MHz; CDCl3):
d
3.59 (s, 2H), 3.84 (s, 3H),
6.98 (d, J¼8.0 Hz, 2H), 7.42 (d, J¼8.0 Hz, 2H), 7.58 (t, J¼7.2 Hz, 2H),
hexane¼1:3). 1H NMR (400 MHz; CDCl3):
d
1.06 (d, J¼6.4 Hz, 6H),
7.65e7.68 (m, 1H), 7.95 (d, J¼8.0, 2H), 7.99 (s, 1H); 13C NMR
3.36e3.45 (m, 1H), 3.78 (s, 3H), 4.73 (s, 1H), 6.85 (d, J¼8.4 Hz, 2H),
7.01e7.05 (m, 1H), 7.22 (d, J¼8.4 Hz, 2H), 7.45e7.51 (m, 3H), 7.90 (d,
(100 MHz, CDCl3): d 16.3, 55.4, 114.7, 115.2, 124.2, 127.7, 128.1, 129.6,
131.7, 134.0, 138.7, 142.3, 161.7; HRMS (EI) calcd for C17H15NO3S
J¼7.2 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 23.9, 46.4, 55.3, 92.3,
(Mþ) m/z 313.0773; found 313.0769.
113.8, 125.7, 127.8, 128.8, 129.1, 132.0, 144.9, 159.7, 160.8; HRMS (EI)
calcd for C18H21NO3S (Mþ) m/z 331.1242; found 331.1243.
6.2.9. 1-((E)-1-(2-Methoxyphenyl)but-1-en-3-yn-2-ylsulfonyl) ben-
zene (22). The trimethylsilyl acetylene (10.0 equiv, 0.52 mL,
3.63 mmol) was dissolved in dry THF (4 mL) and deprotonated with
MeLi$LiBr (2.21 M in Et2O solution, 10.0 equiv, 1.67 mL, 3.63 mmol)
at 0 ꢀC for 1 h, then added into the solution of 4a (100 mg,
0.37 mmol) in dry THF (14.5 mL) at ꢁ40 ꢀC. The mixture was stirred
for 5 h, the reaction was poured into ice-cold saturated NH4Cl,
extracted with ethyl acetate (20 mLꢃ3). The combined organic
layers were washed with brine, dried over MgSO4, and concen-
trated. The residue was purified by chromatography on silica gel
with ethyl acetate and hexane (1:7) as an eluent to afford 22
(27 mg, 25%) as yellow liquid, Rf 0.18 (ethyl acetate/hexane¼1:3)
and 24 together with trace amount 24a (24 mg, 44%). 1H NMR
6.2.14. N-((Z)-1-(2-Methoxyphenyl)-2-(phenylsulfonyl)vinyl) cyclo-
hexanamine (27a). As yellow liquid, Rf 0.33 (ethyl acetate/
hexane¼1:3). 1H NMR (400 MHz; CDCl3):
d 1.08e1.23 (m, 6H), 1.42
(br, 1H), 1.60e1.61 (m, 3H), 2.74e2.78 (m, 1H), 3.73 (s, 3H), 4.47 (s,
1H), 6.86 (d, J¼8.4 Hz, 1H), 6.90 (t, J¼7.6 Hz, 1H), 7.09 (d, J¼7.2 Hz,
1H), 7.30e7.33 (m,1H), 7.43e7.49 (m, 4H), 7.93 (d, J¼7.6 Hz, 2H); 13C
NMR (100 MHz, CDCl3):
d 24.4, 24.5, 25.2, 52.9, 55.4, 88.5, 110.9,
120.5, 124.5, 125.5, 128.6, 129.4, 130.7, 131.7, 145.4, 156.0, 156.8;
HRMS (EI) calcd for C21H25NO3S (Mþ) m/z 371.1555; found 371.1553.
6.2.15. N-((Z)-1-(4-Methoxyphenyl)-2-(phenylsulfonyl)vinyl) cyclo-
hexanamine (27b). As yellow solid mp 119.8e120.8 ꢀC, Rf 0.45
(400 MHz; CDCl3):
d
3.74 (s, 1H), 3.82 (s, 3H), 6.90 (d, J¼8.4 Hz, 1H),
(ethyl acetate/hexane¼1:3). 1H NMR (400 MHz; CDCl3):
d 1.05e1.15

9964
C.-Y. Cheng, M. Isobe / Tetrahedron 67 (2011) 9957e9965
(m, 3H), 1.20e1.29 (m, 2H), 1.46e1.48 (m, 1H), 1.61e1.72 (m, 4H),
2.97e3.07 (m, 1H), 3.80 (s, 3H), 4.70 (s, 1H), 6.83e6.87 (m, 2H),
7.21e7.23 (m, 2H), 7.45e7.52 (m, 3H), 7.90e7.92 (m, 2H); 13C NMR
HRMS (ESI) calcd for C18H16O4SNa (MþNa) m/z 351.0667; found
351.0665.
(100 MHz, CDCl3):
d
24.6, 25.1, 34.3, 53.1, 55.3, 91.9, 113.8, 125.7,
6.2.21. (E)-2,3-Dihydro-3-((phenylsulfonyl)methylene)inden-1-one
(34). The mixture solution of 33 (55 mg, 0.17 mmol), p-toluene-
sulfonic acid monohydrate (318 mg, 1.67 mmol), trimethyl ortho-
127.8, 128.8, 129.1, 131.9, 145.0, 159.7, 160.7; HRMS (EI) calcd for
C21H25NO3S (Mþ) m/z 371.1555; found 371.1551.
ꢀ
formate (0.13 mL, 1.17 mmol), and MS 4 A in methanol (8.5 mL,
6.2.16. 1-((Z)-2-(2-Methoxyphenyl)-2-(phenylthio)vinylsulfonyl)
benzene (28a). To a mixture solution of 4a (100 mg, 0.37 mmol) and
phenyl disulfide (481 mg, 2.20 mmol) in MeOH (18.5 mL) was
added NaBH4 (84 mg, 2.20 mmol) at 0 ꢀC and stirred for 1 h. The
mixture solution was poured into ice-cold saturated aqueous NH4Cl
and extracted with ethyl acetate (20 mLꢃ3). The combined organic
layers were washed with brine, dried over MgSO4, and concen-
trated. The residue was purified by chromatography on silica gel
with ethyl acetate and hexane (1:5) as an eluent to afford 28a
(115 mg, 82%) as colorless liquid, Rf 0.28 (ethyl acetate/
0.02 M) was heated to reflux for 45 h. The reaction solution was
cooled to room temperature, quenched by ice-cold saturated
aqueous NH4Cl, then filtered through Celite. The filtrate was con-
centrated in vacuo, then the water layers were extracted with ethyl
acetate (15 mLꢃ3). The combined organic layers were washed with
brine, dried over MgSO4, and concentrated. The residue was puri-
fied by chromatography on silica gel with ethyl acetate and hexane
(1:4) as an eluent to afford 34 (12 mg, 25%) as a brown liquid, Rf 0.28
(ethyl acetate/hexane¼1:2) together with dimmer byproduct 35
(32 mg, 35%) as yellow liquid, Rf 0.26 (ethyl acetate/hexane¼1:2).
hexane¼1:3).1H NMR (400 MHz; CDCl3):
d
3.54 (s, 3H), 6.41 (s, 1H),
1H NMR (400 MHz; CDCl3):
d
3.77 (s, 2H), 6.93 (s, 1H), 7.54e7.69 (m,
5H), 7.73 (d, J¼7.6 Hz, 1H), 7.83 (d, J¼7.2 Hz, 1H), 7.96 (d, J¼7.6 Hz,
2H); 13C NMR (100 MHz; CDCl3):
40.4, 121.5, 122.3, 124.0, 127.5,
6.44 (d, J¼8.4 Hz, 1H), 6.65e6.68 (m, 1H), 6.92e6.94 (m, 2H),
6.96e7.06 (m, 5H), 7.54e7.58 (m, 2H), 7.61e7.66 (m, 1H), 8.13e8.16
d
(m, 2H); 13C NMR (100 MHz, CDCl3):
d
54.9, 110.2, 119.7, 124.7, 125.2,
129.5, 132.5, 133.8, 135.1, 137.8, 141.2, 146.6, 199.7; IR (KBr) v:1723,
2850, 2922 cmꢁ1; HRMS (ESI) calcd for C16H12O3SNa (MþNa) m/z
307.0405; found 307.0403.
127.4, 127.9, 128.5, 128.7, 129.9, 130.1, 130.4, 133.1, 134.6, 141.6, 155.5,
155.7; HRMS (EI) calcd for C21H18O3S2 (Mþ) m/z 382.0697; found
382.0704.
Acknowledgements
6.2.17. 1-((Z)-2-(4-Methoxyphenyl)-2-(phenylthio)vinylsulfonyl)
benzene (28b). As white solid, mp 116.2e117.1 ꢀC, Rf 0.33 (ethyl
We are grateful to National Science Council, Taiwan and Na-
tional Tsing Hua University for funds supported to the current
studies.
acetate/hexane¼1:3). 1H NMR (400 MHz; CDCl3):
d 3.66 (s, 3H),
6.62 (d, J¼8.8 Hz, 2H), 6.72 (s, 1H), 6.83 (d, J¼6.8 Hz, 2H), 6.96e7.01
(m, 3H), 7.19 (d, J¼8.4 Hz, 2H), 7.51 (t, J¼7.6 Hz, 2H), 7.57e7.61 (m,
1H), 8.14 (d, J¼7.2 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 55.2, 113.6,
Supplementary data
127.7, 128.0, 128.2, 128.5, 128.7, 128.8, 130.2, 131.8, 132.5, 133.2,
141.6, 155.3, 161.0; HRMS (EI) calcd for C21H18O3S2 (Mþ) m/z
382.0697; found 382.0697.
Copies of 1H NMR, 13C NMR and 2D NMR spectra are included as
Supplementary data. The crystallographic data for the structures of
18, 19 and 27b have been deposited with the Cambridge Crystal-
lographic Data Center as Supplementary publications no. CCDC
843905, no. CCDC 843909 and no. CCDC 843910. Copies of the data
can be obtained free of charge on application to CCDC, 12 Union
Road, Cambridge CB2 1EZ, UK (tel.: þ44 (0) 1223 762911; e-mail:
deposit@ccdc.cam.ac.uk). Supplementary data associated with this
article can be found, in the online version, at doi:10.1016/
j.tet.2011.09.078.
6.2.18. 1-(4-Methoxyphenyl)-2-(phenylsulfonyl)ethanone (29b). The
mixture solution of 4b (100 mg, 0.37 mmol) and sodium methoxide
(60 mg, 1.10 mmol) in methanol (18.5 mL) was heated to reflux for
1 h. The reaction solution was cooled to room temperature, and was
neutralized to pH¼7 by Dowex-50W-X4 then filtered. The filtrate
was concentrated in vacuo. The residue was purified by chroma-
tography on silica gel with ethyl acetate and hexane (1:5) as an
eluent to afford 29b (77 mg, 72%) as white solid, mp 113.0e113.5 ꢀC,
Rf 0.18 (ethyl acetate/hexane¼1:3). 1H NMR (400 MHz; CDCl3):
References and notes
d
3.86 (s, 3H), 4.66 (s, 2H), 6.92 (d, J¼8.8 Hz, 2H), 7.50e7.54 (m, 2H),
7.62e7.65 (m, 1H), 7.85e7.87 (m, 2H), 7.90 (d, J¼9.2 Hz, 2H); 13C
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4767e4776.
NMR (100 MHz, CDCl3): d 55.5, 63.2, 114.0, 128.4, 128.7, 129.1, 131.8,
134.1, 138.7, 164.5, 186.1; HRMS (EI) calcd for C15H14O4S (Mþ) m/z
290.0613; found 290.0618.
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white solid, mp 80.9e82.1 ꢀC, Rf 0.48 (ethyl acetate/hexane¼1:3).
1H NMR (400 MHz; CDCl3):
d
5.44 (d, J¼11.6 Hz, 1H), 5.89 (d,
J¼17.6 Hz, 1H), 6.36 (dd, J¼11.6, 17.6 Hz, 1H), 7.36 (s, 3H), 7.48e7.50
(m, 4H), 7.54e7.56 (m, 1H), 7.87 (s, 2H), 7.88 (s, 1H); 13C NMR
(100 MHz, CDCl3):
d 123.8, 126.3, 128.0, 128.5, 128.8, 129.9, 130.3,
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6.2.20. 2-Methyl-2-(2-(2-(phenylsulfonyl)ethynyl)phenyl)-1,3-
dioxolane (33). As white solid, mp 97.5e98.9 ꢀC, Rf 0.33 (ethyl ac-
etate/hexane¼1:5). 1H NMR (400 MHz; CDCl3):
d 1.54 (s, 3H),
3.58e3.67 (m, 2H), 3.87e3.95 (m, 2H), 7.26 (t, J¼7.6 Hz, 1H), 7.39 (t,
J¼7.6 Hz, 1H), 7.50e7.57 (m, 4H), 7.62e7.65 (m, 1H), 8.08 (d,
J¼8.0 Hz, 2H); 13C NMR (100 MHz; CDCl3):
d 25.9, 64.3, 88.8, 93.8,
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