Nucleophilic substitution reaction at an sp2 carbon of vinyl halides with an intramolecular thiol moiety: synthesis of thio-heterocycles

Article abstract of DOI:10.1016/j.tet.2009.06.078

This article presents a full account of intramolecular vinylic substitution reactions of bromoalkenes having an acetylthio moiety, which give sulfur-containing heterocycles such as dihydrothiophene, tetrahydrothiopyran, and 2-alkylidenethietane derivative

Full text of DOI:10.1016/j.tet.2009.06.078

Tetrahedron 65 (2009) 6888–6902
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Nucleophilic substitution reaction at an sp2 carbon of vinyl halides with
an intramolecular thiol moiety: synthesis of thio-heterocycles
Mao-Yi Lei a, Yong-Jun Xiao a, Wei-Min Liu a, Koji Fukamizu b, Shunsuke Chiba a,
,
Kaori Ando c, Koichi Narasaka a
*
a Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore
b Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
c Department of Chemistry, Faculty of Engineering, Gifu University, 1-1 Yanagido Gifu 501-1193, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
This article presents a full account of intramolecular vinylic substitution reactions of bromoalkenes
having an acetylthio moiety, which give sulfur-containing heterocycles such as dihydrothiophene, tet-
rahydrothiopyran, and 2-alkylidenethietane derivatives. The reaction pathways of the substitution re-
actions were investigated by theoretical and experimental studies.
Received 26 December 2008
Received in revised form 29 May 2009
Accepted 19 June 2009
Available online 24 June 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Nucleophilic vinylic substitution
Sulfur-containing heterocycles
SNVs and SNVp mechanisms
Density functional theory (DFT)
1. Introduction
occurs with inversion of the configuration (Scheme 1a). In the SNV
mechanism, a nucleophile interacts with the orbital of the vi-
nylic carbon and gives a substitution product with retention of the
configuration (Scheme 1b). However, both SNV and SNV mech-
p
p
*
Concerted nucleophilic substitution at an sp3 carbon, typically
bimolecular nucleophilic substitution (SN2) reaction, is one of the
most fundamental reactions in organic chemistry, giving a sub-
stitution product with inversion of the configuration.1 For such
a concerted bimolecular nucleophilic substitution at a vinylic (sp2)
carbon are proposed two possible mechanisms, namely, in-plane
vinylic nucleophilic substitution (SNV
nucleophilic substitution (SNV
cleophile attacks to the
s
p
anisms were so far considered as unfavorable processes at unac-
tivated vinylic carbons.3
Recent theoretical studies have provided some information on
these substitution reactions at unactivated vinylic carbons.4 For
example, Glukhovtsev et al. showed that the activation energy
s
) and out-of-plane vinylic
mechanism, a nu-
p
).2 In the SNV
s
(32.6 kcal molꢀ1) of the SNV
s
reaction of vinyl chloride with
a chloride ion is about 10 kcal molꢀ1 lower than that of SNV
(42.7 kcal molꢀ1). Lee reported that in vinylic substitution of
chloroethene by HOꢀ and HSꢀ, SNV
pathway is favored, whereas
the SNV
pathway is preferred in the nucleophilic attack with Cl–
s
*
orbital of C–X bond and the substitution
p
p
Nu
R2
R3
R2
R3
Nu
R1
s
R2
R3
R1
X
R1
and Br–. However, the estimated activation energies of both reaction
pathways in these theoretical studies are so high that the sub-
stitution reactions hardly proceed under mild reaction conditions.
There are few reports on substitution reactions at unactivated
(a)
(b)
–X–
X
+
Nu
R2
R3
R1
Nu–
R2
R3
R1
X
sp2 carbons, which were proposed to proceed via the SNV
s mech-
–X–
anism.5 The substitution reaction of alkenyliodonium salts was
found to give the products with inversion of the stereochemistry.6
2-Bromoallylamines cyclized to aziridines by base treatment and
the stereospecificity of the cyclization suggests that the amino
group approaches from the backside of the bromine atom.7
We also showed that haloalkenes bearing intramolecular alco-
hol, sulfonamide, active methine, and thiol moieties at suitable
positions cyclized to the corresponding 5-membered products by
Nu
(Nu– = nucleophile; X = eliminating group)
Scheme 1.
* Corresponding author. Tel.: þ65 6316 8900; fax: þ65 6791 1961.
E-mail address: narasaka@ntu.edu.sg (K. Narasaka).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.06.078

M.-Y. Lei et al. / Tetrahedron 65 (2009) 6888–6902
6889
intramolecular vinylic substitution.8 The cyclizations with O,N,C-
nucleophiles proceeded only from the E-isomers, with the Z-iso-
mers giving no cyclization products with recovery of the starting
haloalkenes (Scheme 2). This stereospecificity is consistent with our
theoretical studies by DFT calculations, namely, that reactions pro-
Schemes 5 and 6. Dibromination of alkenol 110 followed by dehy-
drobromination under basic conditions11 gave bromoalkenol 2,
which was converted into thioacetate 3 by tosylation of 2 and
successive substitution with potassium thioacetate (Scheme 5). cis-
Reduction of alkyne 412 with DIBAL13 followed by treatment of the
14
ceed via the SNV
s
mechanism.
resulting vinylsilane with Br2
provided E-bromoalkenol 5
(Scheme 6a). The corresponding Z-isomer 8 was prepared by the
reaction of 3-phenylpropanal and allylzinc reagent (Scheme 6b).15
These bromoalkenols 5 and 8 were transformed into thioacetates 6
and 9 via their tosylates, respectively. 5-Bromo-4-alkenyl thio-
acetate 13 for 6-membered ring formation was also synthesized as
shown in Scheme 7. The reaction of 3-methyl-3-butenylmagnesium
bromide and 3-phenylpropanal gave alkenol 11. Introduction of
a bromine atom onto alkene 11 followed by the sequence of tosy-
lation and substitution with potassium thioacetate led to 13.
δ–
X
δ –
Nu
X
Nu =
Nu
O
Nu
–X–
NTs
C(CN)SO2Ph
R
R
R
X = Cl
Br
SNV
Scheme 2.
However, the cyclization reaction with a thiol moiety exhibited
contrasting phenomena with the above nucleophiles, that is, the
cyclization proceeded with both E- and Z-isomers (Scheme 3),
Br
OH
OH
1) Br2, CCl4, rt
which meant SNV
The calculation also suggested relatively small activation energies
for the SNV pathway. In addition, 4-membered ring compounds,
p as a possible reaction pathway for the Z-isomer.
Me
Ph
Me
Ph
2) KOH, MeOH, rt
2 40%
(E : Z = 7 : 1)
1
p
O
2-alkylidenethietanes could be prepared by the cyclization of
S-acetyl 3-bromo-3-alkenethiols.9
Br
S
Me
1) TsCl, pyridine, rt
S
S
Br
Me
Ph
2) AcSK, DMF, 45 °C
SH
NaH (1.5 mol equiv)
3 59%
(E : Z = 7 : 1)
Ph
Ph
Ph
Ph
DMI
(degassed)
50 °C, 6 h
Scheme 5.
E
34%
12%
Br
SH
NaH (1.5 mol equiv)
1) (i-Bu)2AlH
Et2O, 0 °C
Br
OH
TMS
OH
DMI
(degassed)
50 °C, 4 h
Ph
Ph
2) Br2
CH2Cl2, –78 °C
Z
5 57%
4
(a)
O
(DMI = N,N-dimethylimidazolidinone)
Br
S
Me
Ph
Scheme 3.
1) TsCl, pyridine, rt
2) AcSK, DMF, 45 °C
As the nucleophilic vinylic substitution with thiol moieties
exhibited unique characters, we have studied it in detail. This ar-
ticle presents a full account of intramolecular vinylic substitution
reactions of terminal-bromoalkenes A and internal bromoalkenes B
having an acetylthio moiety, which gives sulfur-containing hetero-
cycles such as dihydrothiophene, tetrahydrothiopyran, and 2-alky-
lidenethietane derivatives (Scheme 4).
6 54%
1) ZnBr2, THF, –78 °C
2) LDA
Br
Br
OH
Br
CHO
Ph
Ph
3)
7
Ph
8 62%
(b)
O
1) TsCl, pyridine, rt
S
Me
O
K2CO3
MeOH
S
Br
2) AcSK, DMF, 45 °C
R2
S
Me
9 44%
( )n
R1
R2
R1
( )n
(n = 1, 2)
DMI,
Scheme 6.
A: terminal-bromoalkenes
R3
O
K2CO3
MeOH
R3
R4
1) Br2
CCl4, rt
R4
S
Me
1) Mg
S
Ph
R5
DMI,
Me
( )n
( )n
Me
Br
Br
CHO
(n = 1, 2, 3)
R5
2)
2) KOH
MeOH
rt
Ph
OH
11 33%
10
B: internal-bromoalkenes
THF, rt
Scheme 4.
Br
Me
Br
Me
1) TsCl, pyridine, rt
2. Results and discussion
2.1. Preparation of bromoalkenes
Ph
Ph
2) AcSK, DMF, 45 °C
S
Me
OH
12 43%
(E : Z = 1.7 : 1)
O
13 27%
For 5-membered ring formation from terminal-bromoalkenes A,
4-bromo-3-alkenyl thioacetates 3, 6, 9 were prepared as shown in
Scheme 7.

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M.-Y. Lei et al. / Tetrahedron 65 (2009) 6888–6902
The preparation internal bromoalkenes B for 5- and 6-mem-
28: R = (CH2)2Ph, 91%
29: R = CH2Ph, 33%
30: R = cyclo-C6H11, 92%
31: R = (CH2)4CO2Et, 50%
32: R = p-MeO-C6H4, 50%
R-CHO
Sn powder
aq. HBr
bered ring cyclization are summarized in Schemes 8 and 9. Starting
from known bromoalkenols 1416 and 15,17 oxidation followed by
alkylation with phenethylmagnesium bromide gave 16 and 17,
which were converted to thioacetates 18 and 19, respectively. In
a similar procedure, 5-methyl-4-hexen-1-ol (20)18 was converted
into thioacetate 23.
OH
Br
Br
R
Br
Et2O–H2O
rt
33: R =
, 78%
27
Br
34: R = (CH2)2Ph, 64%
35: R = CH2Ph, 50%
36: R = cyclo-C6H11, 45%
37: R = (CH2)4CO2Et, 48%
38: R = p-MeO-C6H4, 0%
O
R
1) Dess-Martin
periodinane
CH2Cl2, rt
1) TsCl, pyridine, rt
S
Me
2) AcSK, DMF, 45 °C
Br
OH
Ph
( )n
Br
( )n
Br
Br
39: R =
, 52%
OMe
Ph
OH
2) PhCH2CH2MgBr
THF, 0 °C
14 (n = 1)
15 (n = 2)
Br
16 (n = 1) 39%
17 (n = 2) 40%
O
OH
EtO2CN=NCO2Et
PPh3, AcSH
S
Me
1) TsCl, pyridine, rt
Ph
Br
( )n
Br
2) AcSK, DMF, 45 °C
OMe
S
Me
THF, rt
32
38 10%
O
Scheme 11.
18 (n = 1) 54%
19 (n = 2) 59%
Scheme 8.
SiMe3
Br
OH
TiCl4
O
+
Ph
Br
H
Ph
CH2Cl2
–78 °C
1) Dess-Martin
periodinane
CH2Cl2, rt
40
1) Br2
CCl4, rt
Me
Me
Me
Me
Ph
41 76%
(syn : anti = 5 : 1)
OH
Ph
2) Ph(CH2)2MgBr
THF, 0 °C
2) KOH
MeOH
rt
20
OH
21 31%
O
S
Me
Ph
1) TsCl
1) TsCl, pyridine, rt
Me
Me
Me
Br
Me
pyridine, rt
Br
Ph
Me
Ph
2) AcSK, DMF, 45 °C
Br
2) AcSK
DMF, 45 °C
S
OH
22 22%
Ph
42 44%
O
23 59%
Scheme 12.
Scheme 9.
To examine 4-membered ring (2-alkylidenethietanes) forma-
tion, -bromo- -alkenyl thioacetates were prepared as shown in
Both E- and Z bromoalkenyl thioacetates were prepared from
undecanoyl chloride (43) and phosphorus ylide 44.23 The resulting
allene 45 was treated with LiBr in acetic acid,24 and then reduced
with NaBH4, giving a Z and E mixture of homoallylic alcohols 46 and
47 (Scheme 13). After chromatographic separation of the isomers,
g
g
Schemes 10–13. Dibromination of the known homoallylic alcohol
2419 and successive dehydrobromination gave 3-bromo 4,4-di-
methyl homoallylic alcohol 25, which was converted into thio-
acetate 26 (Scheme 10). 3-Bromo homoallylic alcohols 28–33 were
synthesized by the reaction of 2,3-dibromopropene (27) with al-
dehydes in the presence of tin powder,20 and were converted into
the corresponding thioacetates 34–39 by tosylation and sub-
stitution of tosylates with potassium thioacetate or by Mitsunobu
reaction with thioacetic acid21 (Scheme 11).
O
O
O
Et3N
+
R
R
Ph3P
Cl
Ph
CH2Cl2
rt
Ph
45 33%
43
44
(R = n-C9H19
)
For the preparation of b-substituted homoallylic alcohol 41, (Z)-
1) LiBr
b
-bromoallylsilane 40 reacted with 3-phenylpropanal to afford 41
with syn-selectivity (Scheme 12).22 Tosylation of 41 followed by
substitution with potassium thioacetate gave thioacetate 42 having
anti-stereochemistry.
AcOH
R
R
OH
80 °C
OH
+
Br
Ph
Br
Ph
2) NaBH4
MeOH
0 °C
47 8%
1) TsCl
46 21%
1) TsCl
1) Br2
CCl4, rt
Me
Me
OH
Me
Br
Me
OH
pyridine, rt
pyridine, rt
2) AcSK
2) AcSK
Ph
DMF, rt
O
DMF, rt
O
Ph
2) KOH
MeOH, rt
25 63%
24
R
R
O
S
Me
S
Me
Me
Br
Me
S
1) TsCl, pyridine, rt
Me
Ph
Br
Ph
Br
Ph
2) AcSK, DMF, 45 °C
48 55%
49 49%
(R = n-C9H19
)
26 44%
Scheme 13.
Scheme 10.

M.-Y. Lei et al. / Tetrahedron 65 (2009) 6888–6902
6891
thioacetates 48 and 49 were obtained by tosylation followed by
used directly instead of thiol 50 for this intramolecular substitution
reaction. As expected, treatment of thioacetate 3 with 1.5 mol equiv
of NaOMe at room temperature in DMI gave dihydrothiophene 51
in 61% yield (Scheme 14).
substitution with potassium thioacetate (Scheme 13).25
2.2. Intramolecular vinylic substitution reactions
Interestingly, the Z-isomer of 50 was not recovered in these
reactions, which meant that both the E- and Z-stereoisomers were
cyclized to 51. To confirm this, the reactions of E- and Z-bro-
moalkenes 6 and 9 were examined independently (Scheme 15). It is
noteworthy that dihydrothiophene 52 was obtained in 83% and 70%
yields from both stereoisomers 6 and 9, respectively by treatment
with K2CO3 and MeOH in DMI at 120 ꢁC.26
2.2.1. Reactions of terminal-bromoalkenes A
When an E/Z-mixture (7:1) of thiol 50 prepared from thioacetate
3 was treated with NaH in N,N0-dimethylimidazolidin-2-one (DMI),
the cyclization proceeded even at room temperature, giving dihy-
drothiophene 51 in 70% yield (Scheme 14). However, thiol 50 was
found not to be stable enough because it was easily oxidized to the
corresponding disulfide. We envisaged that thioacetate 3 could be
O
K2CO3 (1.5 mol equiv)
Br
S
MeOH (10 mol equiv)
O
S
Me
Ph
Br
Br
SH
S
Me
Ph
KOH
Ph
DMI
(degassed)
120 °C, 5 h
6
52 83%
Me
Ph
Me
MeOH, rt
50 59%
(E : Z = 7 : 1)
3
O
(E : Z = 7 : 1)
K2CO3 (1.5 mol equiv)
MeOH (10 mol equiv)
Br
S
S
Me
Ph
NaH
(1.5 mol equiv)
Ph
S
DMI
(degassed)
120 °C, 3.5 h
Br
Ph
9
S
52 70%
DMI
(degassed)
rt, 9 h
Me
Me
51 70%
Scheme 15.
To get more information on these vinylic substitution reactions,
we carried out theoretical calculations using the Gaussian pro-
gram.27 All calculations were performed at the B3LYP28/6-31þG(d)
level and the solvent effect was included by using the Onsager
O
S
Br
Me
S
NaOMe
Br
S
3
Me
–OMe
DMI
(degassed)
rt, 2 h
continuum model29 for DMF (
3
¼37.06) as a solvent.30 For the
Me
cyclization of the thiolate anion from 3, E-anion E-53 generated
from E-3 gave the SNV
activation energy is 19.6 kcal molꢀ1 in the gas phase and
12.5 kcal molꢀ1 in DMF, respectively. On the other hand, the SNV
s transition structure E-53-ts (Fig. 1). The
Ph
Me
p
51 61%
transition structure Z-54-ts was obtained from Z-isomer Z-3 and its
activation energies are 20.7 kcal molꢀ1 in the gas phase and
Scheme 14.
Figure 1. Transition structures for the nucleophilic cyclization of thiolate anion E-53 and Z-54 [B3LYP/6-31þG(d), SCRF (dipole, solv¼DMF)]. Selected bond lengths are shown in Å.
The italic numbers are the values in the gas phase.

6892
M.-Y. Lei et al. / Tetrahedron 65 (2009) 6888–6902
20.8 kcal molꢀ1 in DMF, respectively (Fig. 1). Thus, the calculation
also suggested that each stereoisomer can cyclized through the
SNVs or SNVp transition states, because their activation energies are
low enough to undergo substitution under the presented reaction
conditions.
This intramolecular nucleophilic substitution was next ap-
plied to 6-membered ring formation using bromoalkene 13.
However, the yield of the cyclized product, tetrahydrothiopyran
55 was low (18%), and we couldn’t confirm whether the sub-
stitution reaction proceeded from the E-isomer or both stereo-
isomers (Scheme 16).
afforded an inseparable mixture of 2-methylenetetrahydrothiophene
56 and 2,3-dihydrothiophene 57 in 85% yield (56/57¼3:1) (Table 1,
entry 1). It was found that 2-methylenetetrahydrothiophene 56
gradually isomerized to 2,3-dihydrothiophene 57 at room tempera-
ture during flash chromatography on silica gel. The reaction of thio-
acetate 23havinganisopropylidenemoietygavetetrahydrothiophene
58 and dihydrothiophene 59 in 59% and 10% yield, respectively
(entry 2). Formation of a 6-membered ring was also examined with
thioacetate 19, affording an inseparable mixture of tetrahy-
drothiopyran 60 and dihydrothiopyran 61 in 31% yield along with
19% yield of dehydrobromination product 62 (entry 3). Tetrahy-
drothiopyran 60 also slowly isomerized to dihydrothiopyran 61
during flash column chromatography on silica gel.
Br
According to the above results, it was found that 5-mem-
bered ring formation proceeded more smoothly than that of
6-membered with both terminal-bromoalkenes A and internal-
bromoalkenes B. Galli and Mandolini reported the kinetics of
ring-closure reactions of 1,1-bis(ethoxycarbonyl)cycloalkanes
K2CO3 (1.5 mol equiv)
MeOH (10 mol equiv)
S
Ph
Ph
Me
Me
S
Me
DMI
(degassed)
120 °C, 10 h
55 18%
O
13
(E : Z = 1.7 : 1)
from the anions derived from diethyl (
u-bromoalkyl)malonates
by intramolecular nucleophilic substitution at an sp3 carbon,
which showed that the order of ring-closing rate was 5>6>4
membered ring formation.31 However, in the case of the intra-
molecular nucleophilic substitution with S-nucleophile at an sp2
carbon, there was no precedent on the reaction rate of ring-
closures.
Next we tried a competitive reaction among 5 versus 4-mem-
bered ring formation using thioacetate 39. Surprisingly, the re-
action of thioacetate 39 gave only the 4-membered ring product,
methylidenethiethane 63, in 87% yield without forming the 5-
membered ring compound (Scheme 17).
Scheme 16.
2.2.2. Reactions of internal-bromoalkenes B
As well as terminal-bromoalkenes A, substitution reactions of in-
ternal-bromoalkenesB with athiolateanionwerefoundtoproceedas
showninTable 1. Formationofa5-memberedringfromthioacetate18
Table 1
Cyclization of internal bromoalkenes B with a thiolate aniona
Entry
Thioacetate
Conditions
Product (yield/%)b
S
O
Ph
1.5 mol equiv. K2CO3
S
Me
S
10 mol equiv. MeOH
56
Br
Br
Br
Br
DMI (degassed)
120 °C, 1.5h
S
Ph
Me
Me
Br
Ph
39
1
120 ꢁC, 7 h
S
57
S
O
(85)
(56 : 57 = 3 : 1)
18
Br
Me
S
Me
Ph
63 87%
58 (59)
S
Me
Br
Me
Scheme 17.
Me
Me
Ph
Me
2
120 ꢁC, 8 h
This alkylidenethietane formation32 prompted us to investigate
the scope and limitations, the results of which are summarized in
Table 2. When thioacetate 26 was treated with 1.5 mol equiv of
K2CO3 and 10 mol equiv of MeOH at 120 ꢁC in degassed DMI, thie-
tane 64 was obtained in 94% yield (Table 2, entry1). Thioacetate
derivatives 34–37 bearing primary and secondary alkyl groups at
C(4)-position cyclized to give 2-methylenethietanes 65–68 in good
yields (entries 2–5). Benzylic thioacetate 38 was cyclized to thie-
tane 69 in moderate yield, due to the concurrent elimination of
thioacetic acid forming a conjugated diene as a side product (entry 6).
3,4-Disubstituted 2-methylenethietane 70 was also formed in 92%
yield (entry 7).
Ph
S
59 (10)
O
23
S
Ph
60
Me
S
Ph
O
61
S
Me
Ph
3
120 ꢁC, 7 h
(31)
(60 : 61 = 2.5 : 1)
Br
O
The theoretical calculation of the cyclization of thiolate anion 71
19
from thioacetate 34 revealed that both SNV
states (Fig. 2) have reasonable activation energies (22.4 kcal molꢀ1
for SNV in DMF) to undergo substitution
, 18.2 kcal molꢀ1 for SNV
reactions.
s and SNVp transition
S
Me
Ph
s
p
62 (19)
We were motivated to investigate the mechanism of this thi-
ethane formation by experimental evidence. As we could not judge
a
Reactions were carried out in degassed DMI with 1.5 mol equiv of K2CO3 and
10 mol equiv of MeOH.
b
Isolated yield.
from the above results which is the real reaction course, the SNV
p

M.-Y. Lei et al. / Tetrahedron 65 (2009) 6888–6902
6893
Table 2
O
R
Synthesis of 2-alkylidenethietanesa
1.5 mol equiv. K2CO3
10 mol equiv. MeOH
R
Br
S
Me
Ph
Thietane (yield/%)b
S
Entry
Thioacetate
Conditions
120 ꢁC, 3 h
DMI (degassed)
120 °C, 1.5h
Me
O
48
Ph
72 70%
S
Me
Br
Me
Me
S
S
Me
Ph
O
1.5 mol equiv. K2CO3
10 mol equiv. MeOH
R
R
Ph
S
Me
Ph
26
64 (94)
O
R
DMI (degassed)
120 °C, 1.5h
Br
S
Ph
1
49
73 62%
S
Me
(R = n-C9H19
)
R
Br
Scheme 18.
2
3
34: R¼(CH2)2Ph
35: R¼CH2Ph
120 ꢁC, 1.5 h
120 ꢁC, 3 h
120 ꢁC, 3 h
120 ꢁC, 10 h
120 ꢁC, 2 h
65 (93)
66 (92)
67 (85)
68 (67)
69 (30)
3. Conclusions
4
36: R¼cyclo-C6H11
5c
6
37: R¼(CH2)4CO2Et
38: R¼p-MeO-C6H4
By the nucleophilic intramolecular substitution reactions of
bromoalkenes bearing an acetylthio moiety, several kinds of sulfur-
containing heterocycles could be synthesized. The experimental
and theoretical studies revealed that the vinylic substitution re-
actions with S-nucleophiles could proceed in either SNVs or SNVp
mechanisms. The present methods would provide unique synthetic
routes for a variety of heterocycles.
O
S
S
Me
Ph
7
120 ꢁC, 1.5 h
Br
Ph
Ph
Ph
70 (92)
42
a
Reactions were carried out in degassed DMI with 1.5 mol equiv of K2CO3 and
10 mol equiv of MeOH.
4. Experimental
4.1. General
b
Isolated yield.
10 mol equiv of EtOH was used instead of MeOH.
c
1H NMR (500, 400 and 300 MHz) spectra were recorded on
Bruker AVANCE 500, 400 and 300 and JEOL AL 400 spectrometers in
CDCl3 [using tetramethylsilane (for 1H,
d
¼0) as internal standard].
or/and SNV
stereochemical outcomes of the thiethane formation, that is,
inversion of configuration should be ovserved for SNV and re-
tention should be for SNV . The cyclization reactions of E and Z
thioaetates 48 and 49 were examined, giving thietanes 72 in 70%
yield and 73 in 62% yield, respectively, with complete retention of
their configurations (Scheme 18).33 Thus, the thietane formation
s mechanism. It would be confirmed by examining the
13C NMR (125, 100 and 75 MHz) spectra were recorded on Bruker
AVANCE 500, 400 and 300, and JEOL AL 400 spectrometers in CDCl3
s
[using CDCl3 (for 13C,
d
¼77.00) as internal standard]. The following
p
abbreviations were used to explain the multiplicities: s¼singlet,
d¼doublet, t¼triplet, q¼quartet, br¼broad. IR spectra were recor-
ded on a Horiba FT 300-S by the ATR method and a Shimazu IR
Prestige-21 FT-IR Spectrometer. High-resolution mass spectra were
obtained with a JEOL MS-700P mass spectrometer and a Finnigan
proceeds with retention of the configuration, namely by the SNV
mechanism.
p
Figure 2. Transition structures for the nucleophilic cyclization of thiolate anion 71 [B3LYP/6-31þG(d), SCRF (dipole, solv¼DMF)]. Selected bond lengths are shown in Å. The italic
numbers are the values in the gas phase.

6894
M.-Y. Lei et al. / Tetrahedron 65 (2009) 6888–6902
MAT 95 XP mass spectrometer (Thermo Electron Corporation) and
Q-Tof Premier. Elemental analyses were carried out at the Ele-
mental Analysis Laboratory, Department of Chemistry, Faculty of
Science, The University of Tokyo. Melting points are uncorrected
and were recorded on a Buchi B-54 melting point apparatus. Flash
column chromatography was performed using Merck silica gel 60
with distilled solvents, and preparative thin-layer chromatography
was carried out using Wakogel B-5F. Dry tetrahydrofuran (THF),
diethyl ether (Et2O), and dichloromethane (CH2Cl2) were taken
from a solvent purification system (PS-400-5, Innovative Technology
Inc.). 1,3-Dimethyl-2-imidazolidinone (DMI) and N,N-dimethyl-
formamide (DMF) were distilled from calcium hydride (CaH2) and
stored over molecular sieves 4 Å (MS 4 Å). Ethanol (EtOH) was
distilled from sodium and stored over molecular sieves 3 Å (MS
3 Å). Methanol was distilled from a trace amount of iodine and
magnesium, and stored over MS 3 Å. Triethylamine and pyridine
were distilled from CaH2 and stored over KOH.
major isomer (E): 1H NMR (400 MHz, CDCl3)
d 7.26–7.30 (2H, m),
7.14–7.21 (3H, m), 5.93–5.94 (1H, m), 3.64–3.71 (1H, m), 2.58–2.80
(2H, m), 2.38–2.40 (2H, m), 2.35 (3H, s), 1.89–1.95 (1H, m), 1.77 (3H,
d, J¼1.2 Hz), 1.73–1.83 (1H, m); 13C NMR (100 MHz, CDCl3)
d 195.4,
141.2, 138.7, 128.5, 128.4, 126.1, 103.9, 44.2, 41.8, 35.6, 33.1, 30.9,
18.8; IR (NaCl): 3063, 3026, 2938, 2916, 2855, 1694, 1682, 1495,
1454, 1354, 1288, 1113, 953, 748, 700 cmꢀ1; HRMS (ESI) found:
349.0224, calcd for C15H19OSBrNa (MþNaþ): 349.0238.
4.2.3. (E)-6-Bromo-1-phenylhex-5-en-3-ol (5)12 (Scheme 6a)
To a stirred solution of 1-phenyl-6-(trimethylsilyl)hex-5-yn-3-ol
(4)12 (770 mg, 3.1 mmol) in Et2O (5 mL) was added DIBAL–H in hep-
tane (1.0 M in heptane) (8.1 mL, 8.1 mmol) at 0 ꢁC, and the mixture
was stirred at room temperature overnight. The reaction mixture was
quenched with methanol (30 mL) and saturated sodium potassium
tartrate solution (30 mL), and the organic materials were extracted
three times with Et2O. The combined organic extracts were washed
with water and brine, dried over MgSO4, and concentrated in vacuo.
The crude product was purified by flash column chromatography
(silica gel, hexane/EtOAc¼20:1) to afford the (Z)-1-phenyl-6-trime-
thylsilyl-hex-5-en-3-ol (500 mg, 2.0 mmol) as colorless oil in 64 %
yield.
4.2. Preparation of starting materials
4.2.1. 6-Bromo-5-methyl-1-phenylhex-5-en-3-ol (2) (Scheme 5)
To a stirred solution of 5-methyl-1-phenylhex-5-en-3-ol (1)10
(5.98 g, 31.4 mmol) in CCl4 (150 mL) was added a solution of bro-
mine (1.7 mL, 33.0 mmol) in CCl4 (50 mL) at 0 ꢁC, and the mixture
was stirred for 2 h. The reaction was quenched with saturated
Na2S2O3 solution at 0 ꢁC, and the organic materials were extracted
two times with CH2Cl2. The combined extracts were washed with
water and brine, dried over MgSO4, and concentrated in vacuo. The
residual brown oil was treated with a 5 M solution of KOH in MeOH
(37 mL) at room temperature for 4 h. The reaction mixture was
quenched with water and extracted three times with Et2O. The
combined organic layer was washed with brine, dried over MgSO4,
and concentrated in vacuo. The crude product was purified by flash
column chromatography (silica gel, hexane/EtOAc¼8:1) to give an
E/Z-mixture (7:1) of 2 (3.40 g, 12.6 mmol) in 40% yield.
To a stirred solution of (Z)-1-phenyl-6-trimethylsilanyl-hex-5-en-
3-ol (290 mg, 1.2 mmol) in CH2Cl2 (4 mL) was added bromine (60 mL,
1.2 mmol) at –78 ꢁC. The reaction mixture was quenched with satu-
rated Na2S2O3 solution and the organic materials were extracted
three times with CH2Cl2. The combined organic extracts were washed
with brine, dried over Na2SO4, and filtered. The filtrate was cooled to
ꢀ20 ꢁC prior to addition of TBAF (610 mg, 2.3 mmol). The mixture
was stirred at ꢀ20 ꢁC for 40 min. The reaction mixture was concen-
trated in vacuo. The crude product was purified by flash column
chromatography (silica gel, hexane/EtOAc¼8:1) to afford (E)-6-
bromo-1-phenylhex-5-en-3-ol (5) (270 mg, 1.1 mmol) in 90% yield.
Yellow oil; Rf¼0.50 (silica gel, hexane/EtOAc¼8:1); 1H NMR
(400 MHz, CDCl3) d 7.28–7.32 (2H, m), 7.20–7.21 (3H, m), 6.12–6.25
Pale yellow oil (E/Z¼7:1); Rf¼0.23 (silica gel, hexane/
(2H, m), 3.65–3.72 (1H, m), 2.77–2.84 (1H, m), 2.65–2.72 (1H, m),
EtOAc¼8:1); data for the major isomer (E): 1H NMR (400 MHz,
2.16–2.31 (2H, m), 1.75–1.81 (3H, m); 13C NMR (100 MHz, CDCl3)
CDCl3)
d
7.27–7.31 (2H, m), 7.18–7.23 (3H, m), 6.00–6.01 (1H, m),
d 141.7, 134.0, 128.5, 128.4, 126.0, 107.0, 69.7, 40.9, 38.4, 32.0; IR
3.74–3.76 (1H, m), 2.66–2.84 (2H, m), 2.22–2.29 (2H, m),1.81 (3H, d,
(NaCl): 3375, 3360, 3061, 3026, 2932, 2860, 1620, 1603, 1495, 1454,
1433, 1275, 1242, 1179, 1084, 1049, 941, 910, 735, 700 cmꢀ1; HRMS
(EI) found: 254.0303, calcd for C12H15OBr (Mþ): 254.0301.
J¼0.8 Hz), 1.75–1.78 (2H, m), 1.55 (1H of –OH, br s); 13C NMR
(100 MHz, CDCl3) d 141.7, 138.7, 128.5, 128.4, 125.9, 103.7, 68.2, 46.5,
38.6, 32.0, 19.3; IR (NaCl): 3447, 3063, 3015, 2940, 2918, 2862, 1628,
1603, 1495, 1454, 1437, 1288, 1217, 1053, 756 cmꢀ1; HRMS (ESI)
found: 291.0366, calcd for C13H17OBrNa (MþNaþ): 291.0360.
4.2.4. (E)-S-6-Bromo-1-phenylhex-5-en-3-yl ethanethioate (6)
(Scheme 6a)
This compound was synthesized from (E)-6-bromo-1-phenyl-
hex-5-en-3-ol (5) according to the same procedure as for 3.
Yellow oil; yield 54% (2 steps); Rf¼0.52 (silica gel, hexane/
4.2.2. S-6-Bromo-5-methyl-1-phenylhex-5-en-3-yl ethanethioate
(3) (Scheme 5)
To a stirred solution of 6-bromo-5-methyl-1-phenylhex-5-en-3-
ol (2) (1.21 g, 4.5 mmol) in pyridine (17 mL) was added p-toluene-
sulfonyl chloride (2.56 g, 13.4 mmol) at 0 ꢁC, and the mixture was
stirred at room temperature overnight. The reaction mixture was
poured into cold water (150 mL) and extracted three times with
Et2O. The combined extracts were washed with aqueous HCl (1 M)
and brine, dried over MgSO4, and concentrated in vacuo. The crude
product was purified by flash column chromatography (silica gel,
hexane/EtOAc¼12:1) to give tosylate (1.42 g, 3.4 mmol) in 75% yield.
To a stirred solution of tosylate (1.38 g, 3.3 mmol) in DMF
(36 mL) was added potassium thioacetate (2.15 g, 18.8 mmol), and
the mixture was stirred at 45 ꢁC for 1 d. The reaction was quenched
with water at 0 ꢁC, and the organic materials were extracted three
times with Et2O. The combined extracts were washed with water
and brine, dried over MgSO4, and concentrated in vacuo. The crude
product was purified by flash column chromatography (silica gel,
hexane/EtOAc¼50:1) to give S-6-bromo-5-methyl-1-phenylhex-5-
en-3-yl ethanethioate (3) (830 mg, 2.5 mmol) in 78% yield. Yellow
oil (E/Z¼7:1); Rf¼0.48 (silica gel, hexane/EtOAc¼8:1); data for the
EtOAc¼10:1); 1H NMR (400 MHz, CDCl3)
d 7.27–7.31 (2H, m), 7.15–
7.22 (3H, m), 6.08–6.18 (2H, m), 3.57–3.63 (1H, m), 2.71–2.78 (1H, m),
2.59–2.66 (1H, m), 2.37–2.42 (2H, m), 2.36 (3H, s),1.79–1.97 (2H, m);
13C NMR (100 MHz, CDCl3)
d 195.3, 141.2, 134.0, 128.5, 128.4, 126.1,
107.1, 43.1, 38.5, 35.6, 33.2, 30.9; IR (NaCl): 3061, 3026, 2924, 2857,
1694, 1618, 1495, 1454, 1435, 1352, 1132, 1113, 945, 750, 700 cmꢀ1
HRMS (EI) found: 312.0090, calcd for C14H17OBrS (Mþ): 312.0178.
;
4.2.5. (Z)-6-Bromo-1-phenylhex-5-en-3-ol (8)12 (Scheme 6b)
To a stirred solution of i-Pr2NH (5.6 mL, 40.0 mmol) in anhy-
drous THF (40 mL) was added dropwise n-BuLi (1.6 M in hexane)
(25.2 mL, 40.0 mmol) at 0 ꢁC, and the reaction mixture was stirred
at 0 ꢁC for 30 min before being transferred into the other flask.
To a stirred solution of ZnBr2 (2.25 g, 10.0 mmol) and allyl bro-
mide (7) (1.7 mL, 20.0 mmol) in THF (80 mL) was added the pre-
formed LDA (40.0 mmol) at ꢀ78 ꢁC, and the mixture was stirred for
around 25 min at ꢀ78 ꢁC. Then hydrocinnamaldehyde (1.0 mL,
8.0 mmol) was added. The reaction mixture was allowed to proceed
for 4 h at ꢀ78 ꢁC. Then the reaction was quenched with aqueous

M.-Y. Lei et al. / Tetrahedron 65 (2009) 6888–6902
6895
HCl (1 M) and the organic materials were extracted three times
4.2.9. S-7-Bromo-6-methyl-1-phenylhept-6-en-3-yl ethanethioate
(13) (Scheme 7)
This compound was synthesized from 7-bromo-6-methyl-
1-phenylhept-6-en-3-ol (12) according to the same procedure as
for 3.
with Et2O. The combined organic extracts were washed with water
and brine, dried over MgSO4, and concentrated in vacuo. The crude
product was purified by flash column chromatography (silica gel,
hexane/ether¼10:1) to afford (Z)-6-bromo-1-phenylhex-5-en-3-ol
(8) (1.26 g, 5.0 mmol) in 62% yield.
Pale yellow oil (E/Z¼1.7:1); yield 27%; Rf¼0.50 (silica gel, hex-
Pale yellow oil; Rf¼0.45 (silica gel, hexane/EtOAc¼4:1); 1H NMR
ane/EtOAc¼8:1); Data for E/Z-isomers: 1H NMR (400 MHz, CDCl3)
(400 MHz, CDCl3)
d
7.27–7.31 (2H, m), 7.20–7.21 (3H, m), 6.30 (1H,
d 7.28–7.30 (2H, m), 7.15–7.21 (3H, m), 5.89–5.90/5.87–5.88 (1H, m),
ddd, J¼1.4, 1.5, 7.0 Hz), 6.21 (1H, ddd, J¼7.0, 7.0, 7.0 Hz), 3.76–3.82
3.51–3.59 (1H, m), 2.59–2.79 (2H, m), 2.36/2.35 (3H, s), 2.11–2.34
(2H, m), 1.81–2.05 (2H, m), 1.78–1.79/1.77–1.78 (3H, m), 1.65–1.77
(1H, m), 2.77–2.85 (1H, m), 2.66–2.74 (1H, m), 2.42–2.46 (2H, m),
1.79–1.85 (2H, m); 13C NMR (100 MHz, CDCl3)
d
141.8, 130.9, 128.5,
(2H, m); 13C NMR (100 MHz, CDCl3)
d 195.6/195.7, 141.4/141.6,
128.4, 125.9, 110.1, 70.1, 38.6, 37.7, 32.0; IR (NaCl): 3374, 3082, 3061,
3024, 2928, 2860, 1622, 1603, 1495, 1454, 1314, 1277, 1080, 1055,
1032, 746, 700, 675 cmꢀ1; HRMS (EI) found: 254.0300, calcd for
C12H15OBr (Mþ): 254.0301.
140.9/140.8, 128.44/128.47, 128.42/128.37, 126.04/125.98, 101.8/
101.3, 43.8/44.1, 36.6/36.4, 33.18/33.21, 33.0/35.5, 31.7/31.8, 30.88/
30.89, 19.2/22.1; IR (NaCl): 3063, 3026, 2934, 2855, 1694, 1632,
1603, 1497, 1454, 1352, 1287, 1132, 1111, 953, 748, 700 cmꢀ1; HRMS
(ESI) found: 363.0391, calcd for C16H21OSBrNa (MþNaþ): 363.0394.
4.2.6. (Z)-S-6-Bromo-1-phenylhex-5-en-3-yl ethanethioate (9)
(Scheme 6b)
4.2.10. 6-Bromo-1-phenylhept-6-en-3-ol (16) (Scheme 8)
This compound was synthesized from (Z)-6-bromo-1-phenyl-
hex-5-en-3-ol (8) according to the same procedure as for 3.
Pale yellow oil; yield 44% (2 steps); Rf¼0.50 (silica gel, hexane/
To a stirred solution of 4-bromopent-4-en-1-ol (14)16 (2.07 g,
12.6 mmol) in anhydrous CH2Cl2 (50 mL) was added Dess–Martin
periodinane (8.30 g, 20.8 mmol) in one portion at room tempera-
ture, and the reaction mixture was stirred at room temperature
overnight. Then the reaction was quenched with saturated Na2S2O3
solution, and the organic materials were extracted three times with
CH2Cl2. The combined extracts were washed with saturated
NaHCO3 solution, water and brine, dried over Na2SO4, and con-
centrated in vacuo. The crude product was purified by flash column
chromatography (silica gel, hexane/EtOAc¼15:1) to give 4-bromo-
pent-4-enal (1.39 g, 8.5 mmol) in 68% yield.
EtOAc¼8:1); 1H NMR (400 MHz, CDCl3)
d 7.25–7.30 (2H, m), 7.16–
7.20 (3H, m), 6.27 (1H, ddd, J¼1.3, 1.4, 7.0 Hz), 6.10 (1H, ddd, J¼7.0,
7.0, 7.0 Hz), 3.65–3.72 (1H, m), 2.72–2.80 (1H, m), 2.62–2.70 (1H,
m), 2.53–2.59 (2H, m), 2.35 (3H, s), 1.82–2.02 (2H, m); 13C NMR
(100 MHz, CDCl3) d 195.5, 141.3,131.3, 128.5, 128.4, 126.0, 110.1, 43.0,
35.9, 35.2, 33.2, 30.8; IR (NaCl): 3084, 3061, 3026, 2922, 2857, 1690,
1622, 1603, 1497, 1454, 1352, 1283, 1132, 1111, 953, 750, 700 cmꢀ1
HRMS (EI) found: 312.0164, calcd for C14H17OBrS (Mþ): 312.0178.
;
To a stirred solution of 4-bromopent-4-enal (1.27 g, 7.8 mmol) in
anhydrous THF (10 mL) was added phenethylmagnesium bromide
(0.7 M in THF) (11.0 mL, 7.8 mmol) at 0 ꢁC, and the reaction mixture
was stirred at room temperature for 4 h. Then the reaction was
quenched with saturated NH4Cl solution, and the organic materials
were extracted three times with Et2O. The combined extracts were
washed with water and brine, dried over MgSO4, and concentrated
in vacuo. The crude product was purified by flash column chro-
matography (silica gel, hexane/EtOAc¼15:1) to give 6-bromo-1-
phenylhept-6-en-3-ol (16) (1.20 g, 4.5 mmol) in 57% yield.
4.2.7. 6-Methyl-1-phenylhept-6-en-3-ol (11) (Scheme 7)
To a stirred suspension of magnesium (300 mg, 12.4 mmol) in
anhydrous THF (20 mL) was added 4-bromo-2-methylbut-1-ene
(10) (1.68 g,11.3 mmol) at 0 ꢁC, and the reaction mixture was stirred
at room temperature for 4 h. The resulting Grignard reagent was
added dropwise via a cannula to a solution of hydrocinnamaldehyde
(1.5 mL, 11.3 mmol) in anhydrous THF (20 mL) at 0 ꢁC, and the re-
action mixture was stirred overnight. The reaction was quenched
with saturated NH4Cl solution at 0 ꢁC, and the organic materials
were extracted three times with Et2O. The combined extracts were
washed with water and brine, dried over MgSO4, and concentrated
in vacuo. The crude product was purified by flash column chroma-
tography (silica gel, hexane/EtOAc¼10:1) to give 6-methyl-1-phenyl-
hept-6-en-3-ol (11) (760 mg, 3.7 mmol) in 33% yield.
Pale yellow oil; Rf¼0.40 (silica gel, hexane/EtOAc¼4:1); 1H NMR
(400 MHz, CDCl3)
d
7.18–7.31 (5H, m), 5.60 (1H, d, J¼1.3 Hz), 5.41
(1H, d, J¼1.3 Hz), 3.67–3.68 (1H, m), 2.52–2.76 (4H, m), 1.66–1.86
(4H, m), 1.42 (1H of –OH, br s); 13C NMR (100 MHz, CDCl3)
d
141.8,
134.3, 128.5, 128.4, 125.9, 116.9, 70.2, 39.2, 37.8, 35.7, 32.0; IR (NaCl):
3364, 3026, 2922, 2857,1630,1495,1454,1435,1082,1057,1030, 887,
746, 698 cmꢀ1; HRMS (ESI) found: 291.0364, calcd for C13H17ONaBr
(MþNaþ): 291.0360.
Pale yellow oil; Rf¼0.22 (silica gel, hexane/EtOAc¼6:1); 1H NMR
(400 MHz, CDCl3)
d 7.24–7.30 (2H, m), 7.18–7.21 (3H, m), 4.70–4.71
(2H, m), 3.63–3.66 (1H, m), 2.76–2.83 (1H, m), 2.63–2.71 (1H, m),
2.04–2.20 (2H, m), 1.76–1.84 (2H, m), 1.72–1.74 (3H, m), 1.56–1.71
(2H, m); 13C NMR (100 MHz, CDCl3)
d
145.8, 142.2, 128.4 (over-
4.2.11. 7-Bromo-1-phenyloct-7-en-3-ol (17) (Scheme 8)
This compound was synthesized from 5-bromohex-5-en-1-ol
(15)17 according to the same procedure as for 16.
lapped), 125.8, 110.2, 71.3, 39.1, 35.3, 34.1, 32.1, 22.5; IR (NaCl): 3358,
3063, 3026, 2934, 2859,1649,1495,1454,1373,1088,1057,1030, 887,
746, 698 cmꢀ1; HRMS (ESI) found: 227.1428, calcd for C14H20ONa
(MþNaþ): 227.1412.
Pale yellow oil; yield 40%; Rf¼0.18 (silica gel, hexane/
EtOAc¼6:1); 1H NMR (400 MHz, CDCl3)
d 7.20–7.31 (5H, m), 5.56
(1H, d, J¼1.1 Hz), 5.40 (1H, d, J¼1.1 Hz), 3.64–3.66 (1H, m), 2.64–2.84
4.2.8. 7-Bromo-6-methyl-1-phenylhept-6-en-3-ol (12) (Scheme 7)
This compound was synthesized from 6-methyl-1-phenylhept-
6-en-3-ol (11) according to the same procedure as for 2.
(2H, m), 2.42–2.46 (2H, m),1.44–1.82 (6H, m),1.41 (1H of –OH, br s);
13C NMR (100 MHz, CDCl3)
d 142.0,134.3,128.42,128.39,125.9,116.7,
71.0, 41.2, 39.1, 36.1, 32.0, 23.9; IR (NaCl): 3377, 3026, 2940, 2860,
1632, 1603, 1495, 1454, 1429, 1123, 1090, 887, 746, 700 cmꢀ1; HRMS
(ESI) found: 305.0523, calcd for C14H19ONaBr (MþNaþ): 305.0517.
Yellow oil (E/Z¼1.7:1); yield 43%; Rf¼0.23 (silica gel, hexane/
1
EtOAc¼8:1); data for E/Z-isomers: H NMR (400 MHz, CDCl3)
d 7.20–
7.31 (5H, m), 5.91–5.93/5.87–5.88 (1H, m), 3.61–3.63 (1H, m), 2.64–2.84
(2H, m), 2.19–2.36 (2H, m),1.56–1.83 (7H, m),1.40 (1H of –OH, br s); 13C
4.2.12. S-6-Bromo-1-phenylhept-6-en-3-yl ethanethioate (18)
(Scheme 8)
NMR (100 MHz, CDCl3)
d 142.1/141.9, 141.5/141.3, 128.49/128.44,
128.39/128.44, 126.0/125.9, 101.5/101.0, 70.7/70.8, 39.2/39.0, 35.2/30.6,
34.5/34.3, 32.0/32.1, 19.2/22.1; IR (NaCl): 3383, 3026, 2934, 2859, 1632,
1603, 1495, 1454, 1375, 1283, 1088, 1030, 746, 700 cmꢀ1; HRMS (ESI)
found: 305.0691, calcd for C14H19OBrNa (MþNaþ): 305.0517.
This compound was synthesized from 6-bromo-1-phenylhept-
6-en-3-ol (16) according to the same procedure as for 3.
Pale yellow oil; yield 54% (2 steps); Rf¼0.53 (silica gel, hexane/
EtOAc¼10:1); 1H NMR (400 MHz, CDCl3)
d 7.16–7.30 (5H, m), 5.56

6896
M.-Y. Lei et al. / Tetrahedron 65 (2009) 6888–6902
(1H, d, J¼1.4 Hz), 5.40 (1H, d, J¼1.4 Hz), 3.54–3.61 (1H, m), 2.45–
m), 2.51–2.55 (1H, m), 1.90 (3H, s), 1.79–1.85 (2H, m), 1.81 (3H, s),
1.75 (1H of –OH, br s); 13C NMR (125 MHz, CDCl3)
141.9, 133.8,
2.79 (4H, m), 2.36 (3H, s), 1.80–2.00 (4H, m); 13C NMR (100 MHz,
d
CDCl3)
d
195.4, 141.4, 133.4, 128.45, 128.38, 126.0, 117.2, 43.3, 38.8,
128.4, 128.3, 125.8, 117.5, 69.7, 45.4, 38.0, 32.1, 25.6, 20.9; IR (ZnSe)
3388, 2918, 1653, 1603, 1496, 1454, 1223, 1043, 933, 746,
698 cmꢀ1; HRMS (FABþ) found: 283.0693, calcd for C14H20BrO
(MþHþ): 283.0698.
36.9, 33.4, 33.2, 30.8; IR (NaCl): 3026, 2924, 2857, 1694, 1682, 1630,
1497, 1454, 1427, 1352, 1113, 953, 889, 748, 700 cmꢀ1; HRMS (ESI)
found: 349.0245, calcd for C15H19ONaSBr (MþNaþ): 349.0238.
4.2.13. S-7-Bromo-1-phenyloct-7-en-3-yl ethanethioate (19)
(Scheme 8)
4.2.18. S-5-Bromo-6-methyl-1-phenylhept-5-en-3-yl ethanethioate
(26) (Scheme 10)
This compound was synthesized from 7-bromo-1-phenyloct-7-
en-3-ol (17) according to the same procedure as for 3.
Pale yellow oil; yield 59% (2 steps); Rf¼0.59 (silica gel, hexane/
This compound was synthesized from 5-bromo-6-methyl-
1-phenylhept-5-en-3-ol (25) according to the same procedure as
for 3.
EtOAc¼8:1); 1H NMR (400 MHz, CDCl3)
d
7.16–7.30 (5H, m), 5.56
Pale yellow oil; yield 44% (2 steps); Rf¼0.68 (silica gel, hexane/
(1H, d, J¼0.9 Hz), 5.40 (1H, d, J¼0.9 Hz), 3.56–3.60 (1H, m), 2.60–
EtOAc¼8:1); 1H NMR (500 MHz, CDCl3)
d 7.26–7.29 (2H, m), 7.16–
2.78 (2H, m), 2.40–2.43 (2H, m), 2.36 (3H, s), 1.84–1.98 (2H, m),
7.20 (3H, m), 3.87–3.93 (1H, m), 2.87 (1H, dd, J¼7.4, 14.7 Hz), 2.75–
2.81 (2H, m), 2.61–2.68 (1H, m), 2.34 (3H, s), 1.99–2.06 (1H, m),
1.82–1.90 (1H, m), 1.87 (3H, s), 1.77 (3H, s); 13C NMR (125 MHz,
1.59–1.70 (4H, m); 13C NMR (100 MHz, CDCl3)
d 195.8, 141.6, 134.1,
128.43, 128.39, 126.0, 117.0, 43.9, 40.9, 36.7, 33.5, 33.2, 30.9, 24.9; IR
(NaCl): 3026, 2938, 2859, 1692, 1628, 1495, 1454, 1352, 1115, 953,
887, 748, 700 cmꢀ1; HRMS (ESI) found: 363.0404, calcd for
C16H21ONaSBr (MþNaþ): 363.0394.
CDCl3)
d 195.3, 141.5, 133.3, 128.3 (overlapped), 125.9, 118.0, 43.9,
42.3, 35.2, 33.2, 30.8, 25.5, 21.0; IR (ZnSe) 2918, 1687, 1603, 1496,
1454, 1352, 1111, 951, 748, 698, 631 cmꢀ1; HRMS (FABþ) found:
341.0573, calcd for C16H22BrOS (MþHþ): 341.0575.
4.2.14. 7-Methyl-1-phenyloct-6-en-3-ol (21)34 (Scheme 9)
This compound was synthesized from 4-bromo-5-methylhex-4-
en-1-ol (20)18 according to the same procedure as for 16.
Pale yellow oil; Yield: 31% (2 steps); Rf¼0.37 (silica gel, hexane/
4.2.19. 5-Bromo-1-phenylhex-5-en-3-ol (28) (Scheme 11)
To a stirred suspension of tin powder (1.59 g, 13.4 mmol) and
2,3-dibromopropene (27) (5.34 g, 26.7 mmol) in Et2O/H2O (1:1,
36 mL) were added a few drops of an aqueous HBr solution and
hydrocinnamaldehyde (1.20 g, 8.9 mmol), and the reaction mixture
was stirred at room temperature for 8 h. The organic materials were
extracted three times with Et2O. The combined extracts were
washed with water and brine, dried over MgSO4, and concentrated
in vacuo. The crude product was purified by flash column chro-
matography (silica gel, hexane/EtOAc¼8:1) to give 5-bromo-1-
phenylhex-5-en-3-ol (28) (2.06 g, 8.1 mmol) in 91% yield.
EtOAc¼7:1); 1H NMR (500 MHz, CDCl3)
d 7.27–7.30 (2H, m), 7.18–
7.22 (3H, m), 5.12–5.15 (1H, m), 3.63–3.67 (1H, m), 2.77–2.83 (1H,
m), 2.65–2.71 (1H, m), 2.03–2.17 (2H, m), 1.72–1.83 (2H, m), 1.70
(3H, s), 1.62 (3H, s), 1.47–1.59 (3H, m); 13C NMR (125 MHz, CDCl3)
d
142.2, 132.2, 128.44, 128.41, 125.8, 124.1, 71.3, 39.2, 37.5, 32.1, 25.7,
24.4, 17.7; IR (NaCl): 3350, 3026, 2965, 2924, 2857, 1603, 1495, 1454,
1375, 1111, 1080, 1059, 1030, 984, 746, 698 cmꢀ1; HRMS (EI) found:
218.1675, calcd for C15H22O (Mþ): 218.1665.
Colorless oil; Rf¼0.33 (silica gel, hexane/EtOAc¼5:1); 1H NMR
4.2.15. 6-Bromo-7-methyl-1-phenyloct-6-en-3-ol (22) (Scheme 9)
This compound was synthesized from 7-methyl-1-phenyloct-6-
en-3-ol (21) according to the same procedure as for 2.
(400 MHz, CDCl3) d 7.27–7.31 (2H, m), 7.17–7.21 (3H, m), 5.70 (1H,
ddd, J¼0.8, 0.8, 1.6 Hz), 5.54 (1H, d, J¼1.6 Hz), 3.95–4.01 (1H, m),
2.84 (1H, ddd, J¼7.6, 7.8, 13.6 Hz), 2.71 (1H, ddd, J¼7.6, 8.6, 13.6 Hz),
2.52–2.67 (2H, m), 1.97 (1H of –OH, br s), 1.79–1.85 (2H, m); 13C
Yellow oil; yield: 22%; Rf¼0.28 (silica gel, hexane/EtOAc¼8:1);
1H NMR (400 MHz, CDCl3)
d
7.27–7.32 (2H, m), 7.17–7.22 (3H, m),
NMR (100 MHz, CDCl3) d 141.8, 130.5, 128.5, 128.4, 125.9, 119.8, 68.6,
3.63–3.65 (1H, m), 2.76–2.83 (1H, m), 2.67–2.73 (1H, m), 2.57–2.65
(2H, m), 1.79–1.85 (2H, m), 1.59–1.70 (2H, m), 1.86 (3H, s), 1.77 (3H,
49.4, 38.0, 32.0; IR (NaCl): 3392, 3061, 3024, 2939, 2858,1629,1602,
1494, 1452, 1078, 1053, 891, 746, 700 cmꢀ1; HRMS (ESI) found:
277.0229, calcd for C12H15OBrNa (MþNaþ): 277.0204.
s); 13C NMR (100 MHz, CDCl3)
d 142.0, 130.7, 128.5, 128.4, 125.9,
121.3, 70.4, 39.3, 36.0, 33.9, 32.1, 25.4, 20.3; IR (NaCl): 3404, 3024,
2922, 2859, 1495, 1454, 1217, 1009, 756, 700, 667 cmꢀ1; HRMS (ESI)
found: 319.0650, calcd for C15H21OBrNa (MþNaþ): 319.0673.
4.2.20. 4-Bromo-1-phenylpent-4-en-2-ol (29) (Scheme 11)
This compound was synthesized from 2,3-dibromopropene
(27) and 2-phenylacetaldehyde according to the same procedure as
for 28.
4.2.16. S-6-Bromo-7-methyl-1-phenyloct-6-en-3-yl ethanethioate
(23) (Scheme 9)
Colorless oil; Yield 33%; Rf¼0.27 (silica gel, hexane/EtOAc¼8:1);
This compound was synthesized from 6-bromo-7-methyl-1-
phenyloct-6-en-3-ol (22) according to the same procedure as for 3.
Yellow oil; yield 59%; Rf¼0.71 (silica gel, hexanes/EtOAc¼8:1);
1H NMR (400 MHz, CDCl3)
d 7.34–7.37 (2H, m), 7.26–7.29 (3H, m),
5.74 (1H, d, J¼1.1 Hz), 5.57 (1H, d, J¼1.1 Hz), 4.19–4.22 (1H, m), 2.88
(1H, dd, J¼4.6, 13.6 Hz), 2.76 (1H, dd, J¼8.4, 13.6 Hz), 2.61 (2H, m);
1H NMR (400 MHz, CDCl3)
d
7.28–7.30 (2H, m), 7.17–7.21 (3H, m),
13C NMR (100 MHz, CDCl3)
d 137.9, 130.5, 129.4, 128.6, 126.6, 119.7,
3.52–3.59 (1H, m), 2.63–2.76 (2H, m), 2.55–2.60 (2H, m), 2.35 (3H,
70.0, 48.6, 42.8; IR (NaCl): 3398, 3062, 3026, 2937, 2857, 1629, 1602,
1494, 1454, 1078, 1043, 891, 746, 700 cmꢀ1; HRMS (ESI) found:
263.0050, calcd for C11H13ONaBr (MþNaþ): 263.0047.
s), 1.72–1.99 (4H, m), 1.85 (3H, s), 1.74 (3H, s); 13C NMR (100 MHz,
CDCl3)
d 195.6, 141.6, 131.0, 128.42, 128.40, 126.0, 120.6, 43.6, 37.1,
35.0, 33.3, 33.1, 30.8, 25.4, 20.3; IR (NaCl): 3024, 2918, 2857, 1692,
1497, 1454, 1352, 1111, 953, 748, 700 cmꢀ1; HRMS (ESI) found:
377.0560, calcd for C17H23OSBrNa (MþNaþ): 377.0551.
4.2.21. 3-Bromo-1-cyclohexylbut-3-en-1-ol (30)35
This compound was synthesized from 2,3-dibromopropene (27)
and cyclohexanecarbaldehyde according to the same procedure as
for 28.
4.2.17. 5-Bromo-6-methyl-1-phenylhept-5-en-3-ol (25)
(Scheme 10)
Colorless oil; yield 92%; Rf¼0.40 (silica gel, hexane/EtOAc¼8:1);
This compound was synthesized from 5-methyl-4-hexen-1-ol
(24)19 according to the same procedure as for 2.
Colorless oil; Yield 63%; Rf¼0.28 (silica gel, hexane/
1H NMR (400 MHz, CDCl3)
d 5.69 (1H, s), 5.53 (1H, s), 3.68–3.72 (1H,
m), 2.60 (1H, dd, J¼2.4, 14.4 Hz), 2.48 (1H, dd, J¼9.6, 14.4 Hz), 1.66–
1.84 (6H, m), 1.36–1.44 (1H, m), 1.10–1.25 (5H, m); 13C NMR
EtOAc¼5:1); 1H NMR (500 MHz, CDCl3)
d
7.27–7.29 (2H, m), 7.22–
(100 MHz, CDCl3)
26.2, 26.1.
d 131.5, 119.5, 72.9, 46.4, 42.9, 29.1, 27.9, 26.4,
7.17 (3H, m), 3.97–4.03 (1H, m), 2.78–2.87 (2H, m), 2.66–2.72 (1H,

M.-Y. Lei et al. / Tetrahedron 65 (2009) 6888–6902
6897
4.2.22. Ethyl 8-bromo-6-hydroxynon-8-enoate (31) (Scheme 11)
4.2.27. S-3-Bromo-1-cyclohexylbut-3-enyl ethanethioate (36)
(Scheme 11)
This compound was synthesized from 2,3-dibromopropene
(27) and ethyl 6-oxohexanoate according to the same procedure as
for 28.
This compound was synthesized from 3-bromo-1-cyclo-
hexylbut-3-en-1-ol (30) according to the same procedure as for 3.
Pale yellow oil; yield 45% (2 steps); Rf¼0.67 (silica gel, hexane/
Colorless oil; yield 50%; Rf¼0.30 (silica gel, hexane/EtOAc¼2:1);
1H NMR (400 MHz, CDCl3)
d
5.69 (1H, d, J¼1.2 Hz), 5.54 (1H, d,
EtOAc¼5:1); 1H NMR (400 MHz, CDCl3)
d
5.62 (1H, d, J¼1.6 Hz),
J¼1.2 Hz), 4.13 (2H, q, J¼7.2 Hz), 3.94–3.96 (1H, m), 2.48–2.58 (2H,
m), 2.30–2.34 (2H, m), 1.81 (1H of –OH, br s), 1.64–1.71 (2H, m),
1.43–1.56 (3H, m), 1.38–1.43 (1H, m), 1.26 (3H, t, J¼7.2 Hz); 13C NMR
5.49 (1H, d, J¼1.6 Hz), 3.84–3.88 (1H, m), 2.75 (1H, dd, J¼6.2,
14.8 Hz), 2.62 (1H, dd, J¼8.8, 14.8 Hz), 2.34 (3H, s), 1.64–1.77 (6H,
m), 0.95–1.26 (5H, m); 13C NMR (100 MHz, CDCl3)
d 195.0, 131.2,
(100 MHz, CDCl3)
d
173.6, 130.5, 119.5, 68.7, 60.3, 49.4, 35.9, 34.2,
118.8, 47.9, 43.9, 40.9, 30.7, 30.5, 28.7, 26.26, 26.25, 26.21; IR (NaCl):
2926, 2850, 1693, 1627, 1448, 1425, 1352, 1195, 1128, 1078, 950, 736,
632 cmꢀ1; HRMS (ESI) found: 291.0421, calcd for C12H20OSBr
(MþHþ): 291.0418.
25.1, 24.8, 14.3; IR (ZnSe) 3446, 2979, 2937, 2912, 2866, 1732, 1631,
1373, 1184, 1155, 1093, 1029, 887, 862 cmꢀ1; HRMS (FABþ) found:
279.0584, calcd for C14H20BrO (MþHþ): 279.0518.
4.2.23. 3-Bromo-1-(4-methoxyphenyl)but-3-en-1-ol (32)
(Scheme 11)
4.2.28. Ethyl 6-(acetylthio)-8-bromonon-8-enoate (37)
(Scheme 11)
This compound was synthesized from 2,3-dibromopropene
(27) and 4-methoxybenzaldehyde according to the same procedure
as for 28.
This compound was synthesized from ethyl 8-bromo-6-
hydroxynon-8-enoate (31) according to the same procedure of
synthesis 3.
Colorless oil; yield 50%; Rf¼0.23 (silica gel, hexane/EtOAc¼4:1);
Pale yellow oil; yield 48% (2 steps); Rf¼0.48 (silica gel, hexane/
1H NMR (500 MHz, CDCl3)
d
7.31 (2H, ddd, J¼2.0, 2.4, 8.8 Hz), 6.89
acetone¼5:1); 1H NMR (400 MHz, CDCl3)
d
5.62 (1H, d, J¼1.6 Hz),
(2H, ddd, J¼2.0, 2.4, 8.8 Hz), 5.66 (1H, d, J¼1.6 Hz), 5.52 (1H, d,
J¼1.6 Hz), 4.97–5.01 (1H, m), 3.81 (3H, s), 2.85 (1H, dd, J¼8.8,
14.4 Hz), 2.73 (1H, dd, J¼3.6, 14.4 Hz), 2.02 (1H of –OH, br s); 13C
5.49 (1H, d, J¼1.6 Hz), 4.13 (2H, q, J¼7.0 Hz), 3.80 (1H, ddd, J¼4.8,
7.6, 14.8 Hz), 2.69 (1H, ddd, J¼7.6, 14.8, 24.4 Hz), 2.32 (3H, s), 2.30
(1H, dd, J¼7.6, 7.6 Hz), 1.55–1.73 (5H, m), 1.38–1.51 (3H, m), 1.48
NMR (125 MHz, CDCl3)
d
159.1, 134.9, 130.1, 127.1, 119.8, 113.8, 71.2,
(3H, t, J¼7.0 Hz); 13C NMR (100 MHz, CDCl3)
d 195.0, 173.4, 130.6,
55.2, 51.1; IR (ZnSe) 3397, 2908, 2835, 1610, 1510, 1464, 1302, 1244,
1174, 1105, 1032, 891, 829 cmꢀ1 found: C, 51.20; H, 5.16%, calcd for
C14H18S: C, 51.38; H, 5.10%.
119.2, 60.3, 46.3, 42.4, 34.2, 33.2, 30.8, 26.2, 24.7, 14.3; IR (ZnSe)
2981, 2937, 2912, 2862,1732,1693,1628,1250,1182,1115,1032, 953,
893, 633 cmꢀ1. Found: C, 46.33; H, 6.27%. Calcd for C14H18S: C,
46.29; H, 6.28%.
4.2.24. 2,7-Dibromoocta-1,7-dien-4-ol (33)36 (Scheme 11)
This compound was synthesized from 2,3-dibromopropene
(27) and 4-bromopent-4-enal according to the same procedure as
for 28.
4.2.29. S-3-Bromo-1-(4-methoxyphenyl)but-3-enyl ethanethioate
(38) (Scheme 11)
To a stirred solution of triphenyl phosphine (1.98 g, 7.5 mmol) inTHF
(19 mL) was added diethyl azodicarboxylate (ca. 2.2 mol Lꢀ1 in toluene,
3.4 mL, 40.4 mmol) at 0 ꢁC and the reaction mixture was stirred at 0 ꢁC
for 10 min. A solution of ethyl 8-bromo-6-hydroxynon-8-enoate (32)
Colorless oil; Yield 78%; Rf¼0.41 (silica gel, hexane/EtOAc¼8:1);
1H NMR (500 MHz, CDCl3)
d
5.71 (1H, d, J¼1.4 Hz), 5.63 (1H, d,
J¼1.4 Hz), 5.56 (1H, d, J¼1.6 Hz), 5.43 (1H, d, J¼1.6 Hz), 3.96–3.98
(1H, m), 2.53–2.66 (4H, m), 1.67–1.84 (3H, m); 13C NMR (75 MHz,
(970 mg, 3.8 mmol) and thioacetic acid (540 mL, 7.6 mmol) in 10 mL of
CDCl3)
d
134.0, 130.2, 119.9, 117.0, 67.9, 49.5, 37.7, 34.6.
THF was added dropwise over 10 min at 0 ꢁC, and the reaction mixture
was stirred for 12 h at room temperature. The solution was concen-
trated, and the residue was purified by flash column chromatography
(silica gel, hexane/methylene chloride¼2:1). Further purification was
conducted by gel permeation chromatography (GPC, CHCl3) togive S-3-
bromo-1-(4-methoxyphenyl)but-3-enyl ethanethioate (38) (119 mg,
0.38 mmol) in 10% yield.
4.2.25. S-5-Bromo-1-phenylhex-5-en-3-yl ethanethioate (34)
(Scheme 11)
This compound was synthesized from 5-bromo-1-phenylhex-5-
en-3-ol (28) according to the same procedure as for 3.
Pale yellow oil; yield 64% (2 steps); Rf¼0.69 (silica gel, hexane/
EtOAc¼5:1); 1H NMR (500 MHz, CDCl3)
d
7.26–7.30 (2H, m), 7.16–
Colorless oil; yield 10%; Rf¼0.46 (silica gel, hexane/EtOAc¼4:1);
7.20 (3H, m), 5.61 (1H, d, J¼1.7 Hz), 5.49 (1H, d, J¼1.7 Hz), 3.83–3.88
1H NMR (500 MHz, CDCl3)
d
7.23 (2H, d, J¼8.6 Hz), 6.83 (2H, d,
(1H, m), 2.69–2.80 (3H, m), 2.63–2.69 (1H, m), 2.35 (3H, s), 1.98–
J¼8.6 Hz), 5.46 (1H, d, J¼1.6 Hz), 5.38 (1H, d, J¼1.6 Hz), 4.90 (1H, dd,
2.05 (1H, m), 1.81–1.91 (1H, m); 13C NMR (125 MHz, CDCl3)
d 195.0,
J¼6.8, 8.8 Hz), 3.78 (3H, s), 2.93–3.05 (2H, m), 2.30 (3H, s); 13C NMR
141.3, 130.5, 128.4, 128.3, 126.0, 119.3, 46.2, 42.3, 35.3, 33.0, 30.8; IR
(ZnSe) 3026, 2937, 2923, 2858, 1689, 1627, 1602, 1496, 1454, 1425,
1354, 1111, 953, 893, 748, 700, 631 cmꢀ1; found: C, 53.74; H, 5.41%,
calcd for C14H18S: C, 53.68; H, 5.47%.
(125 MHz, CDCl3) d 194.1, 158.8, 132.0, 129.9, 128.8, 119.5, 113.9,
55.2, 47.4, 45.7, 30.5; IR (ZnSe) 2956, 2835, 1689, 1610, 1512, 1458,
1423, 1354, 1304, 1252, 1178, 1130, 1107, 1036, 947, 895, 837, 785,
631 cmꢀ1; Anal. calcd for C14H18S: C, 49.53%; H, 4.80%, found:
C,49.76%; H, 4.92%.
4.2.26. S-4-Bromo-1-phenylpent-4-en-2-yl ethanethioate (35)
(Scheme 11)
4.2.30. S-2,7-Dibromoocta-1,7-dien-4-yl ethanethioate (39)
(Scheme 11)
This compound was synthesized from 4-bromo-1-phenylpent-
4-en-2-ol (29) according to the same procedure as for 3.
Pale yellow oil; yield 50% (2 steps); Rf¼0.62 (silica gel, hexane/
This compound was synthesized from ethyl 2,7-dibromoocta-
1,7-dien-4-ol (33) according to the same procedure as for 3.
Yellow oil; yield 52% (2 steps); Rf¼0.68 (silica gel, hexane/
EtOAc¼8:1); 1H NMR (400 MHz, CDCl3)
d 7.28–7.32 (2H, m), 7.23–
7.26 (3H, m), 5.64 (1H, s), 5.52 (1H, s), 4.01–4.08 (1H, m), 2.98 (1H,
EtOAc¼8:1); 1H NMR (400 MHz, CDCl3)
d 5.65 (1H, s), 5.60 (1H, s),
5.52 (1H, d, J¼1.5 Hz), 5.42 (1H, d, J¼1.5 Hz), 3.77–3.84 (1H, m),
dd, J¼7.2, 14.0 Hz), 2.91 (1H, dd, J¼7.6, 14.0 Hz), 2.7 (2H, m), 2.28
(3H, s); 13C NMR (100 MHz, CDCl3)
d
194.9, 138.1, 130.6, 129.3, 128.3,
2.66–2.79 (2H, m), 2.50–2.56 (2H, m), 2.33 (3H, s), 1.97–2.05 (1H,
126.6, 119.4, 45.0, 43.8, 40.0, 30.7; IR (NaCl): 3064, 3030, 2960,
2923, 2857, 1690, 1631, 1598, 1496, 1454, 1425, 1361, 1188, 1174,
1095, 937, 893, 767, 700, 665 cmꢀ1; HRMS (EI) found: 297.9922,
calcd for C13H15OSBr (Mþ): 298.0022.
m), 1.74–1.83 (1H, m); 13C NMR (100 MHz, CDCl3)
d 194.8, 133.1,
130.3, 119.6, 117.4, 46.4, 41.6, 38.7, 32.0, 30.8; IR (NaCl): 2916, 1695,
1628, 1425, 1352, 1184, 1111, 951, 889, 625 cmꢀ1; HRMS (ESI) found:
362.9066, calcd for C10H14ONaSBr2 (MþNaþ): 362.9030.

6898
M.-Y. Lei et al. / Tetrahedron 65 (2009) 6888–6902
4.2.31. (3S
*
,4R
*
)-5-Bromo-4-phenethyl-1-phenylhex-5-en-3-ol
(1.02 g, 11.8 mmol) under N2, and the reaction mixture was stirred
(41)22 (Scheme 12)
at refluxed for 6.5 h. The reaction mixture was quenched with H2O
and then extracted five times with Et2O. The combined organic
layer was washed subsequently with saturated NH4Cl solution,
dried over MgSO4, and concentrated in vacuo. The crude product
was treated with NaBH4 (371 mg, 9.8 mmol) in MeOH (30 mL) at
0 ꢁC, and the reaction mixture was stirred at 0 ꢁC for 5 min. The
reaction was quenched with water at 0 ꢁC, and the organic mate-
rials were extracted three times with CH2Cl2. The combined ex-
tracts were washed with water and brine, dried over Na2SO4, and
concentrated in vacuo. The resulting residue was purified by flash
column chromatography (silica gel, hexane/EtOAc¼15:1) to afford
(Z)-5-bromo-1-phenylpentadec-5-en-3-ol (46) (792 mg, 2.1 mmol)
in 21% yield and (E)-5-bromo-1-phenylpentadec-5-en-3-ol (47)
(299 mg, 0.79 mmol) in 8% yield, respectively.
To
a
stirred solution of bromoallylsilane 4022 (677 mg,
L, 2.7 mmol) in
2.3 mmol) and 3-phenylpropionaldehyde (360
m
CH2Cl2 (23 mL) was added TiCl4 (1 M in CH2Cl2) (2.5 mL, 2.5 mmol)
at ꢀ78 ꢁC, and the reaction mixture was stirred for 5 min. The re-
action was quenched with saturated NaHCO3 solution, and the or-
ganic materials were extracted three times with EtOAc. The
combined extracts were washed with brine and dried over MgSO4,
and concentrated in vacuo. The crude product was purified by flash
column chromatography (silica gel, hexane/EtOAc¼8:1) to give the
syn-diastereomer 41 as well as the anti-diastereomer in 5:1 ratio
(624 mg, 1.7 mmol) in 76% yield.
Colorless oil; Rf¼0.38 (silica gel, hexane/EtOAc¼8:1); data for
the major isomer (syn): 1H NMR (300 MHz, CDCl3)
d 7.27–7.32 (4H,
m), 7.20–7.22 (6H, m), 5.70 (1H, d, J¼1.5 Hz), 5.61 (1H, d, J¼1.5 Hz),
3.60–3.68 (1H, m), 2.80–2.90 (1H, m), 2.60–2.78 (2H, m), 2.39–2.50
(1H, m), 2.21–2.28 (1H, m), 2.04–2.13 (1H, m), 1.87–1.97 (1H, m),
1.78–1.85 (1H, m), 1.64–1.74 (1H, m); 13C NMR (75 MHz, CDCl3)
4.2.34.1. (Z)-5-Bromo-1-phenylpentadec-5-en-3-ol (46). Pale yel-
low oil; Rf¼0.53 (silica gel, hexane/EtOAc¼10:1); 1H NMR
(400 MHz, CDCl3)
d
7.18–7.30 (5H, m), 5.77 (1H, dd, J¼6.8, 6.8 Hz),
d
141.87, 141.85, 135.6, 128.49, 128.48, 128.45 (overlapped), 128.40,
3.94–4.00 (1H, m), 2.51–2.85 (4H, m), 2.15–2.19 (2H, m), 1.78–1.82
125.9, 119.7, 72.8, 55.4, 36.6, 33.1, 32.0, 30.5; IR (NaCl): 3404, 3084,
3026, 2949, 2922, 2860, 1666, 1622, 1602, 1496, 1454, 1253, 1130,
1080, 1049, 908, 748, 698 cmꢀ1; HRMS (EI) found: 358.0804, calcd
for C20H23OBr (Mþ): 358.0927.
(2H, m), 1.71 (1H of –OH, d, J¼2.8 Hz), 1.26–1.41 (14H, m), 0.88
(3H, t, J¼6.9 Hz); 13C NMR (100Mz, CDCl3)
d 141.9, 132.5, 128.4
(overlapped), 125.8, 123.6, 68.5, 49.6, 37.9, 32.0, 31.9, 31.4, 29.5,
29.4, 29.3, 29.2, 28.4, 22.7, 14.1; IR (NaCl): 3377, 3026, 2924, 2853,
1657, 1603, 1495, 1454, 1435, 1076, 1049, 1030, 746, 698 cmꢀ1
;
4.2.32. S-(3R
*
,4R
*
)-5-Bromo-4-phenethyl-1-phenylhex-5-en-3-yl
HRMS (ESI) found: 403.1617, calcd for C21H33OBrNa (MþNaþ):
ethanethioate (42) (Scheme 12)
403.1612.
This compound was synthesized from ethyl (3S
*
,4R )-5-bromo-
*
4-phenethyl-1-phenylhex-5-en-3-ol (41) according to the same
procedure as for 3.
4.2.34.2. (E)-5-Bromo-1-phenylpentadec-5-en-3-ol (47). Pale yel-
low oil; Rf¼0.61 (silica gel, hexane/EtOAc¼10:1); 1H NMR
Pale yellow oil; yield 44% (2 steps); Rf¼0.51 (silica gel, hexanes/
(400 MHz, CDCl3)
d
7.18–7.31 (5H, m), 6.04 (1H, dd, J¼6.7, 6.7 Hz),
EtOAc¼8:1); 1H NMR (300 MHz, CDCl3)
d
7.26–7.32 (4H, m), 7.13–
3.97–4.02 (1H, m), 2.68–2.88 (3H, m), 2.46–2.49 (1H, m), 2.04–2.10
(2H, m), 1.78–1.85 (2H, m), 1.26–1.37 (14H, m), 0.88 (3H, t,
7.23 (6H, m), 5.71 (1H, d, J¼1.5 Hz), 5.65 (1H, d, J¼1.5 Hz), 3.75–3.82
(1H, m), 2.60–2.75 (4H, m), 2.44–2.52 (1H, m), 2.37 (3H, s), 1.74–
J¼6.9 Hz); 13C NMR (100 MHz, CDCl3)
d 141.9, 136.1, 128.5 (over-
2.09 (4H, m); 13C NMR (75 MHz, CDCl3)
d
195.4, 141.5, 141.4, 135.1,
lapped), 125.9, 121.0, 69.2, 43.6, 38.0, 32.2, 31.9, 30.0, 29.5, 29.4,
29.3, 29.24, 29.16, 22.7,14.1; IR (NaCl): 3410, 3026, 2924, 2853,1715,
1495, 1454, 1435, 1078, 1053, 1030, 746, 698 cmꢀ1; HRMS (ESI)
found: 403.1639, calcd for C21H33OBrNa (MþNaþ): 403.1612.
128.49,128.45,128.42 (overlapped),126.03,126.00,120.4, 51.8, 47.0,
34.7, 33.2, 33.1, 32.7, 30.8; IR (NaCl): 3061, 3026, 2927, 2858, 1693,
1681, 1622, 1602, 1494, 1454, 1352, 1130, 1111, 1029, 952, 898, 748,
700, 626 cmꢀ1; HRMS (ESI) found: 417.0882, calcd for C22H26OSBr
(MþHþ): 417.0888.
4.2.35. (Z)-S-5-Bromo-1-phenylpentadec-5-en-3-yl ethanethioate
(48) (Scheme 13)
4.2.33. 1-Phenylpentadeca-4,5-dien-3-one (45) (Scheme 13)
This compound was synthesized from (Z)-5-bromo-1-phenyl-
pentadec-5-en-3-ol (46) according to the same procedure as for 3.
Pale yellow oil; yield 55% (2 steps); Rf¼0.64 (silica gel, hexane/
To a stirred solution of phosphorous ylide 44 (10.2 g, 25.0 mmol)
in CH2Cl2 (50 mL) was added Et3N (3.5 mL, 25.0 mmol) at 0 ꢁC. After
stirring for 5 min at 0 ꢁC, a solution of undecanoyl chloride (43)
(6.66 g, 32.5 mmol) in CH2Cl2 (15 mL) was added dropwise at 0 ꢁC,
and the reaction solution was stirred at room temperature over-
night. After evaporation of the solvent, the residue was treated with
80 mL of Et2O and then filtered. This process was repeated five
times until no further triphenylphosphine oixde precipitated. After
concentration, the crude product was purified by flash column
chromatography (silica gel, hexane/EtOAc¼15:1) to afford 1-phenyl-
pentadeca-4,5-dien-3-one (45) (2.46 g, 8.3 mmol) in 33% yield.
Colorless oil; Rf¼0.56 (silica gel, hexane/EtOAc¼12:1); 1H NMR
EtOAc¼10:1); 1H NMR (400 MHz, CDCl3)
d 7.15–7.29 (5H, m), 5.68
(1H, dd, J¼6.9, 6.9 Hz), 3.85–3.92 (1H, m), 2.61–2.80 (4H, m), 2.34
(3H, s), 1.82–2.17 (4H, m), 1.26–1.37 (14H, m), 0.88 (3H, t, J¼6.7 Hz);
13C NMR (100 MHz, CDCl3)
d 195.1, 141.5, 132.0, 128.4, 128.3, 125.9,
124.0, 46.4, 42.8, 35.3, 33.0, 31.9, 31.3, 30.8, 29.53, 29.45, 29.3, 29.2,
28.3, 22.7, 14.1; IR (NaCl): 2924, 2853, 1694, 1497, 1454, 1352, 1115,
951, 910, 748, 735, 698 cmꢀ1; HRMS (ESI) found: 461.1609, calcd for
C23H35OSBrNa (MþNaþ): 461.1484.
4.2.36. (E)-S-5-Bromo-1-phenylpentadec-5-en-3-yl ethanethioate
(49) (Scheme 13)
(400 MHz, CDCl3)
d 7.28–7.30 (2H, m), 7.17–7.21 (3H, m), 5.73–5.76
(1H, m), 5.56–5.61 (1H, m), 2.90–2.92 (4H, m), 2.10–2.16 (2H, m),
This compound was synthesized from (E)-5-bromo-1-phenyl-
pentadec-5-en-3-ol (47) according to the same procedure as for 3.
Pale yellow oil; yield 49% (2 steps); Rf¼0.68 (silica gel, hexanes/
1.21–1.46 (14H, m), 0.88 (3H, t, J¼6.8 Hz); 13C NMR (100 MHz,
CDCl3) d 212.9, 200.6, 141.2, 128.5, 128.4, 126.1, 97.4, 95.7, 40.6, 31.9,
30.6, 29.5, 29.4, 29.3, 29.2, 28.9, 27.8, 22.7, 14.1; IR (NaCl): 2924,
2853, 1946, 1871, 1724, 1680, 1454, 1155, 746, 698 cmꢀ1; HRMS (ESI)
found: 321.2080, calcd for C21H30ONa (MþNaþ): 321.2189.
EtOAc¼10:1); 1H NMR (400 MHz, CDCl3)
d 7.17–7.30 (5H, m), 5.96
(1H, dd, J¼7.6, 7.6 Hz), 3.87–3.90 (1H, m), 2.63–2.77 (4H, m), 2.35
(3H, s), 1.82–2.09 (4H, m), 1.26–1.36 (14H, m), 0.89 (3H, t, J¼6.8 Hz);
13C NMR (100 MHz, CDCl3)
d 195.1, 141.4, 135.5, 128.4, 128.3, 126.0,
4.2.34. (Z)-5-Bromo-1-phenylpentadec-5-en-3-ol (46) and (E)-5-
bromo-1-phenylpentadec-5-en-3-ol (47) (Scheme 13)
To a stirred solution of 1-phenylpentadeca-4,5-dien-3-one (45)
(2.93 g, 9.8 mmol) in glacial acetic acid (23 mL) was added LiBr
121.3, 43.2, 40.4, 35.3, 33.2, 31.9, 30.8, 30.0, 29.5, 29.4, 29.3, 29.2,
29.1, 22.7, 14.1; IR (NaCl): 2924, 2853, 1694, 1497, 1454, 1130, 1113,
951, 910, 748, 698 cmꢀ1; HRMS (ESI) found: 461.1606, calcd for
C23H35OSBrNa (MþNaþ): 461.1484.

M.-Y. Lei et al. / Tetrahedron 65 (2009) 6888–6902
6899
4.3. Intramolecular vinylic substitution reactions
according to the same procedure of synthesis 52. 2-Methylene-5-
phenethyltetrahydrothiophene (56) gradually tautomerized to give
4.3.1. 4-Methyl-2-phenethyl-2,3-dihydrothiophene (51)
(Scheme 14)
5-methyl-2-phenethyl-2,3-dihydrothiophene
temperature.
(57)
at
room
To a stirred solution of S-6-bromo-5-methyl-1-phenylhex-5-en-
3-yl ethanethioate (3) (48 mg, 0.15 mmol) in degassed DMI (7 mL)
was added NaOMe (16 mg, 0.29 mmol), and the reaction mixture
was stirred at room temperature for 2 h. The reaction was
quenched with pH 9 phosphate buffer solution and Et2O was added.
The layers were separated and the aqueous layer was extracted
three times with Et2O. The combined organic layer was washed
three times with water, then with brine, and dried over MgSO4, and
concentrated in vacuo. The crude product was purified by PTLC
using hexane/EtOAc¼30:1 as an eluent to give 4-methyl-2-phe-
nethyl-2,3-dihydrothiophene (51) (18 mg, 0.09 mmol) in 61% yield.
Colorless oil; Rf¼0.76 (silica gel, hexane/EtOAc¼8:1); 1H NMR
4.3.4.1. Compound 56. Colorless oil; mixture (56/57¼3:1); Rf¼0.28
(silica gel, pure hexane); data for the major isomer 56: 1H NMR
(400 MHz, CDCl3)
d 7.28–7.30 (2H, m), 7.18–7.21 (3H, m), 4.96–4.97
(1H, m), 4.89–4.90 (1H, m), 3.55–3.62 (1H, m), 2.59–2.76 (4H, m),
2.14–2.21 (1H, m), 1.88–2.07 (2H, m), 1.68–1.77 (1H, m).
4.3.4.2. Compound 57. Colorless oil; yield: 85%; Rf¼0.28 (silica gel,
pure hexane); 1H NMR (500 MHz, CDCl3)
d 7.27–7.30 (2H, m), 7.18–
7.19 (3H, m), 5.17–5.18 (1H, m), 3.74–3.79 (1H, m), 2.83–2.87 (1H,
m), 2.71–2.76 (1H, m), 2.62–2.68 (1H, m), 2.44–2.49 (1H, m), 1.96–
2.06 (2H, m), 1.94 (3H, d, J¼1.7 Hz); 13C NMR (125 MHz, CDCl3)
(400 MHz, CDCl3)
d
7.18–7.31 (5H, m), 5.65 (1H, s), 3.73–3.77 (1H,
d 141.6, 136.7, 128.5, 128.4, 125.9, 116.9, 50.6, 42.0, 38.9, 34.3, 16.7; IR
m), 2.63–2.82 (3H, m), 2.37 (1H, dd, J¼6.3, 16.0 Hz), 1.92–2.05 (2H,
(NaCl): 3063, 3021, 2928, 2857, 1713, 1497, 1454, 1358, 1217, 1094,
m), 1.76 (3H, d, J¼0.9 Hz); 13C NMR (100 MHz, CDCl3)
d
141.6, 131.7,
1030, 756, 700 cmꢀ1; HRMS (EI) found: 204.0971, calcd for C13H16
(Mþ): 204.0967.
S
128.5, 128.4, 125.9, 117.0, 49.4, 46.0, 38.9, 34.2, 17.1; IR (NaCl): 3061,
3024, 2957, 2924, 2909, 2851, 2828, 1603, 1495, 1454, 1445, 1435,
1234, 1030, 802, 748, 698 cmꢀ1; HRMS (EI) found: 204.0969, calcd
for C13H16S (Mþ): 204.0967.
4.3.5. 2-Phenethyl-5-(propan-2-ylidene)tetrahydrothiophene (58)
and 5-isopropyl-2-phenethyl-2,3-dihydrothiophene (59) (Table 1,
entry 2)
4.3.2. 2-Phenethyl-2,3-dihydrothiophene (52) (Scheme 15)
To a stirred solution of (E)-S-6-bromo-1-phenylhex-5-en-3-yl
ethanethioate (6) (53 mg, 0.17 mmol) and degassed MeOH (70 mL,
These separated compounds 58 and 59 were synthesized from
S-6-bromo-7-methyl-1-phenyloct-6-en-3-yl ethanethioate (23)
according to the same procedure as for 52.
1.7 mmol) in degassed DMI (8 mL) were added K2CO3 (35 mg,
0.25 mmol), and the reaction mixture was stirred at 120 ꢁC for 5 h.
The reaction was quenched with pH 9 phosphate buffer solution at
0 ꢁC, and the organic materials were extracted three times with Et2O.
The combined extracts were washed with H2O and brine, dried over
MgSO4, and concentrated in vacuo. The crude product was purified
by PTLC using hexane/EtOAc¼50:1 as an eluent to give 2-phenethyl-
2,3-dihydrothiophene (52) (27 mg, 0.14 mmol) in 83% yield.
4.3.5.1. Compound 58. Colorless oil; yield 59%; Rf¼0.45 (silica gel,
hexane/EtOAc¼10:1); 1H NMR (400 MHz, CDCl3)
d 7.17–7.30 (5H,
m), 3.44–3.51 (1H, m), 2.63–2.76 (3H, m), 2.41–2.48 (1H, m), 2.15–
2.22 (1H, m), 1.85–2.04 (2H, m), 1.73 (3H, s), 1.71 (3H, s), 1.68–1.77
(1H, m); 13C NMR (100 MHz, CDCl3)
d 141.6, 132.9, 128.5, 128.4,
125.9, 118.3, 50.0, 38.1, 36.8, 35.1, 32.8, 23.4, 21.4; IR (NaCl): 3061,
3024, 2922, 2851, 1655, 1603, 1495, 1452, 1369, 1236, 1032, 748,
698 cmꢀ1; HRMS (ESI) found: 233.1357, calcd for C15H21S (MþHþ):
233.1364.
Colorless oil; Rf¼0.61 (silica gel, hexane/EtOAc¼10:1); 1H NMR
(400 MHz, CDCl3)
d 7.27–7.31 (2H, m), 7.18–7.21 (3H, m), 6.12–6.14
(1H, m), 5.53–5.56 (1H, m), 3.71–3.79 (1H, m), 2.83–2.91 (1H, m),
2.63–2.79 (2H, m), 2.47–2.53 (1H, m), 1.92–2.06 (2H, m); 13C NMR
4.3.5.2. Compound 59. Colorless oil; yield 10%; Rf¼0.59 (silica gel,
(100 MHz, CDCl3)
d
141.5, 128.5, 128.4, 125.9, 125.0, 121.4, 49.4, 41.4,
hexane/EtOAc¼10:1); 1H NMR (400 MHz, CDCl3)
d 7.17–7.30 (5H,
38.6, 34.3; IR (NaCl): 3061, 3024, 2928, 2833, 1734, 1601, 1497, 1452,
1244, 1043, 1030, 910, 789, 748 cmꢀ1; HRMS (EI) found: 190.0805,
calcd for C12H14S (Mþ): 190.0811.
The compound 2-phenethyl-2,3-dihydrothiophene (52) was
also synthesized from (Z)-S-6-bromo-1-phenylhex-5-en-3-yl
ethanethioate (9) according to the above procedure.
m), 5.19–5.21 (1H, m), 3.67–3.74 (1H, m), 2.82–2.88 (1H, m), 2.62–
2.77 (2H, m), 2.43–2.56 (2H, m), 1.91–2.03 (2H, m), 1.13 (6H, d,
J¼6.8 Hz); 13C NMR (100 MHz, CDCl3)
d 149.3, 141.7, 128.5, 128.4,
125.9, 113.2, 49.4, 41.6, 38.7, 34.3, 30.6, 22.3; IR (NaCl): 3024, 2963,
2930, 2855, 1707, 1497, 1452, 1215, 1030, 756 cmꢀ1; HRMS (EI)
found: 232.1273, calcd for C15H20S (Mþ): 232.1280.
4.3.3. 5-Methyl-2-phenethyl-3,4-dihydro-2H-thiopyran (55)
(Scheme 16)
This compound was synthesized from S-7-bromo-6-methyl-1-
phenylhept-6-en-3-yl ethanethioate (13) according to the same
procedure as for 52.
4.3.6. 2-Methylene-6-phenethyltetrahydro-2H-thiopyran (60), 6-
methyl-2-phenethyl-3,4-dihydro-2H-thiopyran (61) and S-1-
phenyloct-7-yn-3-yl ethanethioate (62) (Table 1, entry 3)
These compounds were synthesized in a mixture (60/61¼2.5:1)
and 62 from S-7-bromo-1-phenyloct-7-en-3-yl ethanethioate (19)
according to the same procedure of synthesis 52. 2-Methylene-6-
phenethyltetrahydro-2H-thiopyran (60) gradually tautomerized to
give 6-methyl-2-phenethyl-3,4-dihydro-2H-thiopyran (61) at room
temperature.
Pale yellow oil; yield 18%; Rf¼0.61 (silica gel, hexane/
EtOAc¼10:1); 1H NMR (500 MHz, CDCl3)
d 7.27–7.30 (2H, m), 7.18–
7.21 (3H, m), 5.69 (1H, s), 2.95–3.00 (1H, m), 2.77–2.83 (1H, m),
2.68–2.74 (1H, m), 2.03–2.10 (3H, m), 1.88–1.93 (2H, m), 1.76–1.82
(1H, m), 1.72 (3H, s); 13C NMR (125 MHz, CDCl3)
d 141.7, 128.5, 128.4
(overlapped), 125.9, 111.4, 38.6, 37.2, 33.1, 30.0, 28.4, 25.0; IR (NaCl):
3061, 3024, 2959, 2922, 2849, 2833, 1634, 1603, 1495, 1445, 1265,
1030, 831, 797, 739, 698 cmꢀ1; HRMS (EI) found: 218.1123, calcd for
C14H18S (Mþ): 218.1124.
4.3.6.1. Compound 60. Pale yellow oil; mixture (60/61¼2.5:1);
Rf¼0.60 (silica gel, pure hexane); data for the major isomer 60: 1H
NMR (400 MHz, CDCl3) d 7.17–7.29 (5H, m), 5.14–5.15 (1H, m), 5.05–
5.06 (1H, m), 2.69–2.85 (2H, m), 2.13–2.55 (3H, m), 1.91–2.05 (1H,
m),1.89–2.05 (4H, m),1.62–1.72 (1H, m); 13C NMR (100 MHz, CDCl3)
4.3.4. 2-Methylene-5-phenethyltetrahydrothiophene (56) and 5-
methyl-2-phenethyl-2,3-dihydrothiophene (57) (Table 1, entry 1)
These compounds were synthesized in a mixture (56:57¼3:1)
from S-6-bromo-1-phenylhept-6-en-3-yl ethanethioate (18)
d 141.7, 128.5, 128.4, 127.8, 125.9, 116.3, 40.4, 37.5, 32.9, 28.7, 23.9,
23.6; IR (NaCl): 3061, 3024, 3011, 2928, 2914, 2841,1713,1495, 1452,
1447, 1435, 1217, 1115, 754, 698 cmꢀ1; HRMS (EI) found: 218.1125,
calcd for C14H18S (Mþ): 218.1124.

6900
M.-Y. Lei et al. / Tetrahedron 65 (2009) 6888–6902
4.3.6.2. Compound 61. Pale yellow oil; yield 31%; Rf¼0.60 (silica gel,
pure hexane); 1H NMR (400 MHz, CDCl3)
7.17–7.29 (5H, m), 5.47–
7.26 (1H, m), 7.19–7.22 (2H, m), 4.99 (1H, ddd, J¼2.0, 2.0, 2.2 Hz),
4.75 (1H, ddd, J¼2.2, 2.4, 2.4 Hz), 3.94–3.87 (1H, m), 3.63–3.56 (1H,
m), 3.30–3.23 (1H, m), 3.16 (1H, dd, J¼6.8, 14.0 Hz), 3.09 (1H, dd,
d
5.50 (1H, m), 3.04–3.10 (1H, m), 2.69–2.85 (2H, m), 2.13–2.24 (2H,
m), 1.89–2.05 (3H, m), 1.87 (3H, d, J¼1.3 Hz), 1.62–1.71 (1H, m); 13C
J¼8.4, 14.0 Hz); 13C NMR (100 MHz, CDCl3)
d 140.5, 138.6, 128.6,
NMR (100 MHz, CDCl3)
d
141.7, 128.5, 128.4, 127.8, 125.9, 116.3, 40.4,
128.5,126.7,103.6, 44.7, 43.3, 39.1; IR (NaCl): 3026, 2914, 2835,1633,
1496, 1452, 1120, 1072, 1030, 831, 750, 721 cmꢀ1; HRMS (EI) found:
176.0653, calcd for C11H12S: 176.0654.
37.5, 32.9, 28.7, 23.9, 23.6; IR (NaCl): 3061, 3024, 3011, 2928, 2914,
2841, 1713, 1495, 1452, 1447, 1435, 1217, 1115, 754, 698 cmꢀ1; HRMS
(EI) found: 218.1125, calcd for C14H18S (Mþ): 218.1124.
4.3.11. 2-Methylene-4-cyclohexylthietane (67) (Table 2, entry 4)
This compound was synthesized from S-3-bromo-1-cyclo-
hexylbut-3-enyl ethanethioate (36) according to the same pro-
cedure as for 52.
4.3.6.3. Compound 62. Colorless oil; yield 19%; Rf¼0.55 (silica gel,
hexane/EtOAc¼10:1); 1H NMR (400 MHz, CDCl3)
d 7.28–7.36 (2H, m),
7.08–7.21 (3H, m), 3.56–3.60 (1H, m), 2.71–2.78 (1H, m), 2.61–2.68
(1H, m), 2.35 (3H, s), 2.18–2.22 (2H, m), 1.77–1.99 (4H, m), 1.52–1.73
Colorless oil; yield 85%; Rf¼0.58 (silica gel, hexane/
(3H, m); 13C NMR (100 MHz, CDCl3)
d
195.7, 141.6, 128.42, 128.38,
acetone¼19:1); 1H NMR (400 MHz, CDCl3)
d
4.91 (1H, ddd, J¼2.0,
126.0, 84.0, 68.7, 43.9, 36.9, 34.0, 33.2, 30.8, 25.6,18.2; IR (NaCl): 3294,
2.0, 2.2 Hz), 4.69 (1H, ddd, J¼2.2, 2.4, 2.4 Hz), 3.47–3.54 (1H, m),
3.33–3.39 (1H, m), 3.19–3.25 (1H, m), 1.60–1.75 (5H, m), 1.52–1.57
(1H, m), 1.10–1.26 (3H, m), 0.76–0.87 (2H, m); 13C NMR (100 MHz,
3026, 2940, 2859, 1688, 1497, 1454, 1354, 1113, 953, 748, 700 cmꢀ1
HRMS (EI) found: 260.1238, calcd for C16H20OS (Mþ): 260.1229.
;
CDCl3)
d 141.2, 103.0, 45.3, 44.2, 42.0, 29.9, 28.8, 26.1, 25.75, 25.73;
4.3.7. 2-(3-Bromobut-3-enyl)-4-methylenethietane (63)
(Scheme 17)
IR (NaCl): 2922, 2852, 1631, 1448, 1124, 825, 748, 651 cmꢀ1; HRMS
(EI) found: 168.0970, calcd for C10H16S: 168.0976.
This compound was synthesized from S-2,7-dibromoocta-1,7-
dien-4-yl ethanethioate (39) according to the same procedure as
for 52.
4.3.12. Ethyl 5-(2-methylenethietan-4-yl)pentanoate (68) (Table 2,
entry 5)
Colorless oil; yield 87%; Rf¼0.65 (silica gel, hexane/EtOAc¼20:1);
This compound was synthesized from ethyl 6-(acetylthio)-
8-bromonon-8-enoate (37) according to the same procedure as
for 52.
1H NMR (400 MHz, CDCl3)
d
5.57 (1H, d, J¼1.4 Hz), 5.41 (1H, d,
J¼1.4 Hz), 4.96 (1H, d, J¼1.9 Hz), 4.72 (1H, d, J¼1.9 Hz), 3.61–3.68
(2H, m), 3.15–3.18 (1H, m), 2.37–2.47 (2H, m), 2.12–2.19 (1H, m),
Pale yellow oil; yield 67%; Rf¼0.56 (silica gel, hexane/
2.00–2.07 (1H, m); 13C NMR (100 MHz, CDCl3)
d
140.5, 132.9, 117.4,
acetone¼5:1); 1H NMR (400 MHz, CDCl3)
d 4.92–4.93 (1H, m),
103.8, 43.5, 39.1, 37.1, 36.6; IR (NaCl): 2918, 2853, 1715, 1628, 1443,
1428, 1360, 1215, 1115, 889, 758, 665 cmꢀ1; HRMS (EI) found:
217.9811, calcd for C8H11BrS (Mþ): 217.9759.
4.68–4.69 (1H, m), 4.11 (2H, q, J¼7.2 Hz), 3.56–3.66 (2H, m), 3.07–
3.15 (1H, m), 2.27–2.31 (2H, m), 1.74–1.90 (2H, m), 1.58–1.69 (2H,
m), 1.26–1.30 (2H, m), 1.24 (3H, t, J¼7.2 Hz); 13C NMR (100 MHz,
CDCl3)
d 173.3, 140.9, 103.4, 60.2, 43.7, 38.4, 38.4, 34.2, 26.8, 24.5,
4.3.8. 2-Isopropylene-4-phenethylthietane (64) (Table 2, entry 1)
This compound was synthesized from S-5-bromo-6-methyl-1-
phenylhept-5-en-3-yl ethanethioate (26) according to the same
procedure as for 52.
14.3; IR (ZnSe) 2979, 2935, 2856, 1732, 1633, 1373, 1234, 1180, 1120,
1030, 831, 650 cmꢀ1; HRMS (FABþ) found: 215.1080, calcd for
C11H18O2S (MþHþ): 215.1028.
Colorless oil; yield 94%; Rf¼0.37 (silica gel, hexane/
4.3.13. 2-Methylene-4-(p-methoxyphenyl)thietane (69)
(Table 2, entry 6)
This compound was synthesized from S-3-bromo-1-(4-
methoxyphenyl)but-3-enyl ethanethioate (38) according to the
same procedure as for 52.
acetone¼19:1); 1H NMR (500 MHz, CDCl3)
d 7.19–7.22 (2H, m), 7.08–
7.13 (3H, m), 3.39–3.49 (2H, m), 2.92–2.95 (1H, m), 2.63–2.57 (1H,
m), 2.46–2.52 (1H, m),1.97–2.11 (2H, m),1.45 (3H, s),1.39 (3H, s); 13C
NMR (125 MHz, CDCl3)
d 141.1, 128.48, 128.43, 125.9, 120.9, 120.0,
40.8, 40.7, 36.5, 33.5, 18.4, 17.7; IR (ZnSe) 2908, 1691, 1603, 1496,
1446, 1369, 1030, 748, 698 cmꢀ1; found: C, 76.75; H, 8.21%, calcd for
C14H18S: C, 77.01; H, 8.31%.
Colorless oil; yield 30%; Rf¼0.37 (silica gel, hexane/
acetone¼19:1); 1H NMR (500 MHz, CDCl3)
d
7.32 (2H, dd, J¼2.8,
11.6 Hz), 6.83 (2H, dd, J¼2.8, 11.6 Hz), 6.20–6.23 (1H, m), 5.56 (1H,
ddd, J¼2.4, 2.8, 3.2 Hz), 4.88 (1H, dd, J¼7.6, 9.6 Hz), 3.79 (3H, s), 3.15
(1H, dddd, J¼2.4, 2.8, 9.6, 16.4 Hz), 2.88 (1H, dddd, J¼2.4, 2.8, 7.6,
4.3.9. 2-Methylene-4-phenethylthietane (65) (Table 2, entry 2)
This compound was synthesized from S-5-bromo-1-phenylhex-
5-en-3-yl ethanethioate (34) according to the same procedure as
for 52.
16.4 Hz); 13C NMR (125 MHz, CDCl3)
d 158.7, 135.4, 128.0, 125.5,
120.5, 113.8, 55.3, 52.4, 43.9; IR (ZnSe) 2999, 2952, 2931, 2906,
2833, 1610, 1583, 1509, 1458, 1302, 1246, 1176, 1109, 1034, 831, 769,
671, 650 cmꢀ1; HRMS (FABþ) found: 193.0686, calcd for C11H12OS
(MþHþ): 193.0609.
Pale yellow oil; yield 93%; Rf¼0.55 (silica gel, hexane/
acetone¼19:1); 1H NMR (500 MHz, CDCl3)
d
7.28 (2H, dd, J¼7.3,
7.5 Hz), 7.14–7.21 (3H, m), 4.94 (1H, ddd, J¼2.0, 2.0, 2.2 Hz), 4.71
(1H, ddd, J¼2.2, 2.4, 2.4 Hz), 3.60–3.65 (1H, m), 3.58 (1H, dddd,
J¼2.0, 2.2, 7.1, 7.6 Hz), 3.14 (1H, dddd, J¼2.0, 2.4, 7.1, 14.8 Hz), 2.62–
2.68 (1H, m), 2.53–2.59 (1H, m), 2.07–2.20 (2H, m); 13C NMR
4.3.14. (3R
*
,4R )-2-Methylene-3,4-diphenethylthietane (70)
*
(Table 2, entry 7)
This compound was synthesized from S-(3R
*
,4R )-5-bromo-4-
*
(125 MHz, CDCl3)
d
141.0, 141.0, 128.4 (overlapped), 126.0, 103.5,
phenethyl-1-phenylhex-5-en-3-yl ethanethioate (42) according to
the same procedure as for 52.
43.5, 40.3, 37.9, 33.5; IR (ZnSe) 3026, 2917, 2852, 1631, 1496, 1454,
1120, 1076, 1030, 831, 748, 698, 650 cmꢀ1; HRMS (FABþ) found:
191.0867, calcd for C12H15S (MþHþ): 191.0816.
Colorless oil; yield 92%; Rf¼0.51 (silica gel, hexane/
acetone¼19:1); 1H NMR (400 MHz, CDCl3)
d 7.28–7.35 (4H, m),
7.15–7.26 (6H, m), 5.00 (1H, dd, J¼2.0, 2.1 Hz), 4.74 (1H, dd, J¼2.1,
2.2 Hz), 3.32–3.42 (2H, m), 2.59–2.68 (3H, m), 2.50–2.57 (1H, m),
2.07–2.18 (2H, m), 1.93–2.01 (2H, m); 13C NMR (100 MHz, CDCl3)
4.3.10. 2-Methylene-4-benzylthietane (66) (Table 2, entry 3)
This compound was synthesized from S-4-bromo-1-phenyl-
pent-4-en-2-yl ethanethioate (35) according to the same procedure
as for 52.
d
145.8, 141.5, 141.0, 128.5 (overlapped), 128.4, 128.3, 126.1, 126.0,
102.7, 56.0, 45.5, 40.0, 36.4, 33.8, 32.4; IR (NaCl): 3024, 2929, 2852,
1627, 1602, 1494, 1452, 1126, 1074, 1030, 833, 748, 698 cmꢀ1; HRMS
(ESI) found: 295.1485, calcd for C20H23S (MþHþ): 295.1520.
Colorless oil; yield 92%; Rf¼0.57 (silica gel, hexane/
acetone¼19:1); 1H NMR (400 MHz, CDCl3)
d 7.29–7.33 (2H, m), 7.23–

M.-Y. Lei et al. / Tetrahedron 65 (2009) 6888–6902
6901
4.3.15. (Z)-2-Decylidene-4-phenethylthietane (72) (Scheme 18)
This compound was synthesized from (Z)-S-5-bromo-1-phe-
nylpentadec-5-en-3-yl ethanethioate (48) according to the same
procedure as for 52.
Colorless oil; yield 99%; Rf¼0.35 (silica gel, pure hexane); 1H
NMR (400 MHz, CDCl3) d 7.76–8.14 (3H, m), 7.38–7.55 (4H, m), 3.34
(2H, t, J¼9.7 Hz), 2.64 (2H, dt, J¼3.2, 9.7 Hz), 2.08 (1H, t, J¼3.2 Hz);
13C NMR (100 MHz, CDCl3)
d
136.3, 133.9, 131.6, 128.9, 127.3, 126.2,
Colorless oil; yield: 70%; Rf¼0.93 (silica gel, hexane/EtOAc¼10:1);
126.1,125.6,125.5,123.4, 83.9, 69.2, 32.1,19.9; IR (NaCl): 3294, 3048,
1H NMR (400 MHz, CDCl3)
d
7.17–7.29 (5H, m), 5.18–5.20 (1H, m),
2932, 2870, 2118,1597,1508,1458,1431,1396,1250,1018, 795 cmꢀ1
;
3.69–3.75 (1H, m), 2.82–2.88 (1H, m), 2.63–2.77 (2H, m), 2.45–2.49
(1H, m), 2.23–2.26 (2H, m), 1.92–2.03 (2H, m), 1.26–1.54 (14H, m),
HRMS (ESI) found: 181.1025, calcd for C14H13 (MþHþ): 181.1017.
0.88 (3H, t, J¼6.7 Hz); 13C NMR (100 MHz, CDCl3)
d
142.3,141.7,128.5,
4.3.21. (Z)-2-Decylidene-4-phenethylthietan-1,1-dioxide (78)
(Ref. 33)
128.4, 125.9, 115.4, 49.8, 41.7, 38.8, 34.3, 31.9, 31.3, 29.6, 29.4, 29.3,
29.1, 28.7, 22.7, 14.1; IR (NaCl): 3024, 2924, 2853, 1497, 1437, 1260,
1030, 908, 735, 698 cmꢀ1; HRMS (EI) found: 316.2216, calcd for
C21H32S (Mþ): 316.2219.
To a stirred solution of (Z)-2-decylidene-4-phenethylthietane
(72) (79 mg, 0.25 mmol) in CH2Cl2 (10 mL) was added m-CPBA
(231 mg, 1.0 mmol) and NaHCO3 (63 mg, 0.75 mmol), and the re-
action mixture was stirred at room temperature overnight. The
reaction was quenched with saturated Na2S2O3 solution, and
the organic materials were extracted three times with CH2Cl2. The
combined extracts were washed with brine, dried over MgSO4, and
concentrated in vacuo. The crude product was purified by flash
column chromatography (silica gel, hexane/EtOAc¼6:1) to give (Z)-
4.3.16. (E)-2-Decylidene-4-phenethylthietane (73) (Scheme 18)
This compound was synthesized from (E)-S-5-bromo-1-phenyl-
pentadec-5-en-3-yl ethanethioate (49) according to the same pro-
cedure as for 52.
Colorless oil; yield 62%; Rf¼0.93 (silica gel, hexane/EtOAc¼10:1);
1H NMR (400 MHz, CDCl3)
d
7.15–7.30 (5H, m), 5.00–5.04 (1H, m),
2-decylidene-4-phenethylthietan-1,1-dioxide
0.20 mmol) in 81% yield.
(78)
(70 mg,
3.49–3.68 (2H, m), 3.02–3.05 (1H, m), 2.53–2.69 (2H, m), 2.07–2.21
(2H, m),1.85–1.90 (2H, m),1.20–1.30 (14H, m), 0.88 (3H, t, J¼6.8 Hz);
Pale yellow oil; yield 81%; Rf¼0.49 (silica gel, hexane/
13C NMR (100 MHz, CDCl3)
d
141.1, 128.50, 128.46, 128.43, 126.0,
EtOAc¼6:1); 1H NMR (400 MHz, CDCl3)
d 7.28–7.32 (2H, m), 7.21–
120.1, 41.1, 40.6, 38.5, 33.6, 31.9, 29.64, 29.61, 29.5, 29.4, 29.2, 28.2,
22.7, 14.1; IR (NaCl): 3024, 2922, 2851, 1663, 1603, 1454, 1302, 1240,
908, 698 cmꢀ1; HRMS (EI) found: 316.2229, calcd for C21H32S (Mþ):
316.2219.
7.24 (3H, m), 6.17–6.18 (1H, m), 3.12–3.20 (1H, m), 2.79–2.91 (3H,
m), 2.32–2.41 (4H, m), 1.87–1.96 (1H, m), 1.57–1.65 (2H, m), 1.26–
1.38 (12H, m), 0.88 (3H, t, J¼6.6 Hz); 13C NMR (100 MHz, CDCl3)
d
145.0, 140.3, 129.9, 128.6, 128.5, 126.3, 57.2, 33.0, 31.8, 31.3, 30.3,
29.4, 29.22, 29.18, 29.1, 27.3, 24.0, 22.6, 14.1; IR (NaCl): 2924, 2853,
1736, 1651, 1603, 1497, 1454, 1437, 1292, 1138, 1119, 912, 750, 735,
700 cmꢀ1; HRMS (ESI) found: 371.2214, calcd for C21H32O2NaS
(MþNaþ): 371.2015.
4.3.17. (E)-1-(4-Bromobut-3-enyl)naphthalene (74) (Ref. 26)
This compound was synthesized from 1-(but-3-ynyl)naph-
thalene (77) according to the reported method.37
Colorless oil; yield 48%; Rf¼0.54 (silica gel, hexane/Et2O¼50:1);
1H NMR (400 MHz, CDCl3)
d
7.73–8.00 (3H, m), 7.30–7.55 (4H, m),
4.3.22. (E)-2-Decylidene-4-phenethylthietan-1,1-dioxide (79)
(Ref. 35)
6.27–6.34 (1H, m), 6.08–6.11 (1H, m), 3.18 (2H, t, J¼7.8 Hz), 2.48–
2.53 (2H, m); 13C NMR (100 MHz, CDCl3)
d
137.3, 136.9, 134.0, 131.7,
This compound was synthesized from (E)-2-decylidene-4-phen-
ethylthietane (73) according to the same procedure as for 78.
Pale yellow oil; yield 85%; Rf¼0.61 (silica gel, hexane/EtOAc¼6:1);
128.9, 127.0, 126.2, 126.0, 125.6, 125.5, 123.5, 105.1, 34.0, 32.2; IR
(NaCl): 3063, 3009, 2940, 2870, 2249, 1620, 1597, 1508, 1458, 1438,
1396, 1250, 1215, 934, 907, 799 cmꢀ1; HRMS (ESI) found: 283.0076,
calcd for C14H13BrNa (MþNaþ): 283.0098.
1H NMR (400 MHz, CDCl3)
d 7.29–7.32 (2H, m), 7.19–7.24 (3H, m),
6.29–6.33 (1H, m), 4.07–4.12 (1H, m), 2.70–2.88 (3H, m), 2.35–2.44
(1H, m), 2.26–2.32 (1H, m), 2.02–2.09 (3H, m), 1.26–1.45 (14H, m),
4.3.18. (Z)-1-(4-Bromobut-3-enyl)naphthalene (75) (Ref. 26)
This compound was obtained from 1-(4,4-dibromobut-3-
enyl)naphthalene according to the reported method.38
Colorless oil; yield 74%; Rf¼0.54 (silica gel, hexane/Et2O¼50:1);
0.88 (3H, t, J¼6.7 Hz); 13C NMR (100 MHz, CDCl3)
d 151.3,140.1,132.4,
128.6,128.5,126.4, 72.6, 33.4, 31.8, 31.5, 29.4, 29.3, 29.24, 29.16, 28.5,
28.0, 24.0, 22.6, 14.1; IR (NaCl): 2926, 2855, 1738, 1680, 1603, 1497,
1454, 1300, 1150, 1128, 912, 750, 735, 700 cmꢀ1; HRMS (ESI) found:
371.1992, calcd for C21H32O2NaS (MþNaþ): 371.2015.
1H NMR (300 MHz, CDCl3)
d 7.73–8.11 (3H, m), 7.34–7.54 (4H, m),
6.18–6.25 (2H, m), 3.20 (2H, d, J¼7.8 Hz), 2.62–2.73 (2H, m); 13C
NMR (100 MHz, CDCl3) d 137.2,134.0,133.9,131.9,128.9,127.0,126.1,
Acknowledgements
126.0, 125.6, 125.5, 123.7, 108.6, 31.4, 30.8; IR (NaCl): 3044, 3005,
2936, 2866, 1620, 1597, 1508, 1458, 1439, 1396, 1304, 1288, 1250,
1022, 795 cmꢀ1; HRMS (ESI) found: 283.0114, calcd for C14H13BrNa
(MþNaþ): 283.0098.
We acknowledge the Nanyang Technological University for
funding of this research.
References and notes
4.3.19. S-1,5-Diphenylpentan-3-yl ethanethioate (76) (Ref. 26)
This compound was prepared from 1,5-diphenylpentan-3-ol39
by following the same procedure as for 3.
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Pale yellow oil; yield 38% (2 steps); Rf¼0.63 (silica gel, hexane/
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d 7.28–7.30 (4H, m), 7.15–
7.21 (6H, m), 3.60–3.66 (1H, m), 2.61–2.78 (4H, m), 2.38 (3H, s),
1.85–2.02 (4H, m); 13C NMR (100 MHz, CDCl3)
d 195.7, 141.6, 128.45,
128.40, 126.0, 44.2, 36.9, 33.2, 30.9; IR (NaCl): 3059, 3024, 2932,
2855, 1690, 1601, 1493, 1454, 1354, 1111, 953, 748 cmꢀ1; HRMS (ESI)
found: 299.1477, calcd for C19H23OS (MþHþ): 299.1470.
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that intermolecular substitution reactions of
b-halostyrenes with thiolate and
enyl)naphthalene according to the reported method.40
selenide anions occur with retention of the configuration, but the reaction

6902
M.-Y. Lei et al. / Tetrahedron 65 (2009) 6888–6902
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Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.;
Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.;
Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao,
O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.;
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13. Marko, I. E.; Dobbs, A. P.; Scheirmann, V.; Chelle, F.; Bayston, D. J. Tetrahedron
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K. B. J. Am. Chem. Soc. 1991, 113, 4776.
30. DMI has an almost the same dielectric constant (37.60) as DMF. Since DMF and
DMI are able to dissolve many salts and tend to surround metal cations rather
than nucleophilic anions, the use of free anions as model systems could be
approved.
31. Casadei, M. A.; Galli, C.; Mandolini, L. J. Am. Chem. Soc. 1984, 106, 1051.
32. For reports on the synthesis of 2-alkylidenethietane derivatives, see: Bolster,
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74, 459.
33. The stereochemistries of the alkenes 72 and 73 were determined by NOE
measurements of the corresponding sulfones 78 and 79, which were prepared
by oxidation of 72 and 73 with m-chloroperbenzoic acid (m-CPBA) as shown
below.
23. Fu, C.; Ma, S. Eur. J. Org. Chem. 2005, 3942.
24. Ma, S.; Xie, H.; Wang, G.; Zhang, J.; Shi, Z. Synthesis 2001, 5, 713.
25. The stereochemistries of the alkenes 48 and 49 were determined by NOE
experiments.
n-C8H17
n-C8H17
H
n-C8H17
H
H
H
H
O
S
m-CPBA
Br
AcS
H
Br
H
H
NaHCO3
O
72
Ph
CH2Cl2, rt
AcS
Ph
H
H
Ph
48
49
78 81%
26. To check the E,Z-isomerization of bromoalkenes 6 and 9 in Scheme 15, E- and
Z-bromoalkenes 74 and 75 were treated with thioacetate 76, K2CO3 and MeOH
under the same reaction conditions as those in Scheme 15. E-Bromoalkene 74
was recovered in 81% yield without contamination of Z-bromoalkene 75. Al-
though Z-bromoalkene 75 was also recovered in 27% without the isomerization,
alkyne 77 was isolated in 50% yield. Based on these observations, the possibility
of bromoalkene isomerization–substitution sequence was excluded from the
cyclizations of both 6 and 9 in Scheme 15. In the cyclization of Z-bromoalkene 9,
an alternative mechanism such as formation of alkyne followed by cyclization to
dihydrothiophene 52 might be proposed. However, the cyclization of an E/Z-
mixture of bromoalkene 3, which has no possibility of alkyne formation, gave
dihydrothiophene 51 without recovery of the Z-isomer. Moreover, the alkyne
formation is slower as compared with the cyclization. Accordingly, nucleophilic
substitution pathway is most likely for the reaction mechanism of the cyclization
of both bromoalkenes 6 and 9 as shown in Scheme 15. For a report of the for-
mation of dihydrothiophenes from sulfur–alkyne cyclizations, see: McDonald, F.
E.; Burova, S. A.; Huffman, L. G., Jr. Synthesis 2000, 7, 970.
n-C8H17
O
S
m-CPBA
O
NaHCO3
H
H
73
CH2Cl2, rt
H
H
Ph
79 85%
34. Chen, S.-L.; Hu, Q.-Y.; Loh, T.-P. Org. Lett. 2004, 6, 3365.
35. Kurosu, M.; Lin, M.-H.; Kishi, Y. J. Am. Chem. Soc. 2004, 126, 12248.
36. Fang, Y.-W.; Li, C.-Z. J. Am. Chem. Soc. 2007, 129, 8092.
37. Flamme, E. M.; Roush, W. R. Org. Lett. 2005, 7, 1411.
38. Uenishi, J.; Kawahama, R.; Yonemitsu, O. J. Org. Chem. 1998, 63, 8965.
39. Ueki, H.; Chiba, T.; Yamazaki, T.; Kitazume, T. J. Org. Chem. 2004, 69, 7616.
40. Schmittel, M.; Mahajan, A. A.; Bucher, G.; Bats, J. W. J. Org. Chem. 2007, 72, 2166.
Br
K2CO3 (1.5 mol equiv)
MeOH (10 mol equiv)
O
S
Me
Ph
SM recovery 81%
DMI
(degassed)
120 °C, 5 h
+
+
Ph
Ph
74
76
Br
O
K2CO3 (1.5 mol equiv)
MeOH (10 mol equiv)
S
Me
Ph
DMI
(degassed)
75
76
120 °C, 3.5 h
77 50% (SM recovery 27%)