Synthesis of hetero- and carbocycles by nucleophilic substitution at sp2 carbon

Article abstract of DOI:10.1016/j.tet.2007.02.116

Vinylic halides having alcohol, sulfonamide, active methine, and thiol moieties as nucleophiles cyclize to hetero- and carbocycles by intramolecular nucleophilic substitution at the sp² carbon centers. The density functional theory calculations suggest that the cyclization proceeds through S_N2-type substitution (the in-plane vinylic nucleophilic substitution, S_NVσ), when vinyl halides are substituted with oxygen, nitrogen, and carbon nucleophiles. The substitution with sulfur nucleophiles, in contrast, proceeds through both routes of S_NVσ and out-of-plane vinylic nucleophilic substitution (S_NVπ).

Full text of DOI:10.1016/j.tet.2007.02.116

Tetrahedron 63 (2007) 5940–5953
Synthesis of hetero- and carbocycles by nucleophilic
substitution at sp2 carbon
a,
Hironori Miyauchi,a Shunsuke Chiba,a Koji Fukamizu,a Kaori Andob, and Koichi Narasaka
*
*
aDepartment of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
bCollege of Education, University of the Ryukyus, 1 Senbaru, Nisihara-cho, Okinawa 903-0213, Japan
Received 12 January 2007; revised 24 February 2007; accepted 27 February 2007
Available online 2 March 2007
Abstract—Vinylic halides having alcohol, sulfonamide, active methine, and thiol moieties as nucleophiles cyclize to hetero- and carbocycles
by intramolecular nucleophilic substitution at the sp2 carbon centers. The density functional theory calculations suggest that the cyclization
proceeds through SN2-type substitution (the in-plane vinylic nucleophilic substitution, SNVs), when vinyl halides are substituted with
oxygen, nitrogen, and carbon nucleophiles. The substitution with sulfur nucleophiles, in contrast, proceeds through both routes of SNVs
and out-of-plane vinylic nucleophilic substitution (SNVp).
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
a stable anion intermediate and the successive elimination of
a leaving group completes the reaction (Scheme 1b). Other-
wise, the lifetime of the intermediate becomes short enough
and the reaction occurs in one step. It is called as SNVp
mechanism because a nucleophile interacts with the p*
orbital of the vinylic carbons (Scheme 1c). There is another
possibility named SNVs mechanism where a nucleophile
attacks the s* orbital of C–X bond of a vinylic carbon
(Scheme 1d).
Bimolecular nucleophilic substitution reaction (SN2) is one
of the most fundamental reactions in organic chemistry. A
nucleophile (Nuꢀ) approaches an sp3 carbon from the oppo-
site side of a leaving group (X), and the bond formation
(Nu–C) and the bond cleavage (C–X) occur concertedly
without any intermediates (Scheme 1a).1 On the contrary,
the nucleophilic substitution on a vinylic sp2 carbon is sup-
posed to have many mechanistic possibilities.2 The most
common pathway is an addition–elimination route, in which
a nucleophile attacks the p-bond. If the double bond has an
electron-withdrawing group, the nucleophilic addition gives
The SNVs mechanism has been considered as an unfavor-
able process. In-plane attack of nucleophile is undesirable
due to steric repulsion,3 and an early theoretical study also
denied the possibility of the SNVs pathway.4 However,
recent studies suggested the possibilities as follows. Theo-
retical calculations done by Glukhovtsev show that the
in-plane nucleophilic attack of a chlorine ion to chloroethene
has about 10 kcal molꢀ1 lower activation energy as com-
pared to the out-of-plane attack.5 Following this discovery,
several theoretical studies have been published on the
SNVs reaction.6 Furthermore, experimental supports have
been provided recently for the substitution reaction at sp2
atoms. The substitution reactions of alkenyliodonium salts
were found to give the products with inversion of stereo-
chemistry via intermolecular SNVs mechanism.7 2-Bromo-
allylamines cyclized to aziridines by vinylic substitution and
the stereochemistry of the products suggests that the amino
group approaches from the backside of the bromo groups.8
We also previously showed that haloalkenes having an intra-
molecular hydroxy group gave the corresponding cyclized
products, such as benzofurans and dihydrofurans, in good
yields.9 Because intramolecular vinylic substitution is con-
sidered to become a powerful tool for the synthesis of cyclic
compounds and its mechanistic study is also of interest, we
Nu–
–
–
–X–
(a)
X
Nu
X
Nu
R2
R3
R1
R2
R3
R1
–X–
–X–
(b)
(c)
Nu
X
Nu
R2
R3
R1
X
–
Nu
R2
R3
R1
R2
R1
R3
–
+
Nu
X
Nu–
–
Nu
R2
R3
R2
R3
Nu
R1
–X–
R1
(d)
–
X
Scheme 1. Bimolecular nucleophilic substitution (SN2) reaction.
Keywords: Haloalkenes; Nucleophilic substitution; Cyclization; Density
functional theory.
* Corresponding authors. Tel.: +81 3 5841 4343; fax: +81 3 5800 6891
(K.N.); e-mail: narasaka@chem.s.u-tokyo.ac.jp
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.02.116

H. Miyauchi et al. / Tetrahedron 63 (2007) 5940–5953
5941
were motivated to investigate the scope and the mechanism
of the intramolecular vinylic substitution with various intra-
molecular nucleophiles.
Bromoalkenols 5 were synthesized by dibromination of the
corresponding alkenols 4 followed by dehydrobromination
under basic conditions.10 Alkenyl bromides bearing nitrogen
nucleophiles (7) were prepared from the above alcohols 5
by the Mitsunobu reaction with N-tert-butoxycarbonyl tosyl-
amide.11 The tert-butoxylcarbonyl (Boc) group of 6 was
removed under acidic conditions. Halo stylene derivative
10 was prepared from commercially available 2-aminoace-
tophenone 8 by chloroalkenylation with a Wittig reagent12
and then sulfonylation of the amino group (Scheme 4).
Here, we wish to report the cyclization of vinyl halides bear-
ing hydroxy, sulfonamide, active methine, and thiol counter-
parts to clarify the difference between the nucleophilic
moieties. Firstly, the preparation of starting materials and
the experimental results of the cyclization reactions are
described successively, and then these reaction mechanisms
are discussed later.
Br Boc
R1
Ts
R2
Br
R1
Ts
R2
Br
N
HN
OH
R2
OH
R2
a
b
c
2. Results and discussion
R1
R1
6a–d
7a–d
4a–d
5a–d
2.1. Preparation of starting materials
a R1=Me R2=(CH2)2Ph c R1=Me R2=H
d R1=(CH2)2Ph R2=H
b R1=Me R2=Ph
Haloalkenes bearing a hydroxy group were prepared as
previously described (Schemes 2 and 3).9
Me
Me
Me
Cl
Cl
Me
Me
Me
e
d
O
Cl
a
O
NH
Ts
+
NH2
NH2
Cl
OMOM
OMOM
OMOM
8
9
10
b
b
Scheme 4. Preparation of bromo- and chloroalkenes with nitrogen nucleo-
philic moieties. Reagents and conditions: (a) Br2, CCl4, rt, then KOH,
MeOH, rt, 40% (5a, E/Z-mixture, 10:1), 31% (5b, E/Z-mixture, 7:1), 57%
(5c, E-isomer: 49%, Z-isomer: 8%, separated), 47% (5d, E-isomer: 35%,
Z-isomer: 12%, separated). (b) BocNHTs, diethyl azodicarboxylate, PPh3,
THF, rt, 50% (6a, E-isomer: 44%, Z-isomer: 6%, separated), 72% (6b,
E-isomer: 63%, Z-isomer: 9%, separated), 83% (E-6c), 95% (E-6d). (c)
CF3CO2H, CH2Cl2, rt, 92% (E-7a), 77% (Z-7a), 94% (E-7b), 84% (E-7c),
91% (E-7d). (d) Ph3PCHCl, THF, rt, 24 h, 70% (9, E-isomer: 63%, Z-iso-
mer: 7%, separated). (e) TsCl, pyridine, CH2Cl2, rt, 12 h, 75% (E-10),
63% (Z-10). Boc¼tert-butoxycarbonyl; Ts¼p-toluenesulfonyl; THF¼tetra-
hydrofuran. For detailed information of E/Z-separation, see Section 5.
Me
Me
Cl
Cl
OH
Z-1
OH
E-1
Me
Me
Me
Br
c, d, e
O
+
Br
OMOM
OMOM
OMOM
f
f
Alkenyl bromides with an active methine moiety (11) were
prepared from 5 by the Mitsunobu reaction with 2-phenyl-
sulfonylacetonitrile (Scheme 5).13
Me
Me
Br
Br
OH
OH
E-2
Br
CN
SO2Ph
Br
OH
Z-2
a
R
R
Scheme 2. Preparation of chloroalkenes having an aromatic hydroxy group.
Reagents and conditions: (a) Cp2TiCl2, Mg, CHCl3, P(OEt)3, MS 4A, THF,
rt, 2 h, 31% (E-isomer), 35% (Z-isomer). (b) HCl aq, THF, rt, 2 h, 99%
(E-1), 81% (Z-1), 98% (E-2), 94% (Z-2). (c) LiCHBr2, THF, ꢀ78 ꢁC, 1 h,
66%. (d) Me3SiCl, imidazole, CH2Cl2, rt, 3 h, 92%. (e) n-BuLi, THF,
ꢀ78 ꢁC, 1 h, 40% (E-isomer), 27% (Z-isomer). (f) HCl aq, THF, rt, 2 h,
98% (E-2), 94% (Z-2). Cp¼cyclopentadienyl; MOM¼methoxymethyl.
5c,d
11c,d
(c R=Me d R=(CH2)2Ph)
Scheme 5. Preparation of bromoalkene with an active methine part.
Reagents and conditions: (a) NCCH2SO2Ph, azodicarbonyldipiperidine,
P(n-Bu)3, THF, rt, 56% (E-11c), 41% (E-11d), 30% (Z-11d).
Cl
Cl
H
O
OH
OMOM
Ph
OMOM
Ph
Alkenyl bromides having a thiol part 13 and 17 were
prepared from bromoalkenyl alcohols 5 and 15, respectively,
by the Mitsunobu reaction with thioacetic acid,14 followed
by the removal of the acetyl group from 12 and 16 under
basic conditions (Scheme 6).
H
H
a, b
+
Ph
c
c
Cl
Cl
H
OH
Ph
OH
2.2. Cyclization of phenols and alcohols
H
Ph
When chloroalkene E-1 was treated with NaH in dimethyl-
formamide (DMF) at room temperature, benzofuran 18
was obtained in 95% yield (Table 1, entry 1), whereas Z-1
was recovered quantitatively even after heating at 110 ꢁC
(entry 2). Under the same reaction conditions (NaH, rt),
bromoalkene E-2 was converted to benzofuran 18 in 73%
E-3
Z-3
Scheme 3. Preparation of chloroalkenes having an aliphatic hydroxy group.
Reagents and conditions: (a) MOMCl, i-Pr2NEt, CH2Cl2, rt, overnight,
93%. (b) Cp2TiCl2, Mg, CHCl3, P(OEt)3, MS 4A, THF, rt, overnight,
80% (E/Z-mixture). (c) HCl aq, THF, 60 ꢁC, 7 h, 44% (E-3), 56% (Z-3).

5942
H. Miyauchi et al. / Tetrahedron 63 (2007) 5940–5953
Br
R1
Br
Br
yield, while Z-2 gave only 6% yield of 18 after a prolonged
SAc
R2
SH
R2
OH
R2
b
a
reaction time along with 87% recovery of Z-2 (entries 3 and
4). An E-isomer of chloroalkene having an aliphatic hydroxy
group (E-3) was also cyclized to give dihydrofuran 19 in
82% yield by heating at 80 ꢁC (entry 5). The product 19
was not obtained from Z-3 (entry 6). The possibility of
6p-electrocyclization could be excluded, because the non-
conjugated compound E-3 also gave the product 19.
R1
R1
5a,d
12a,d
13a,d
a R1=Me R2=(CH2)2Ph
d R1=(CH2)2Ph R2=H
Me
OH
Me
Me
OH
Me
Me
SAc
Me
Br
Me
SH
Me
Br
e
d
c
R3
R3
Br
R3
R3
14
15
16
17
A mixture of E- and Z-deuterated chloroalkenes 1D was
treated with NaH in DMF at room temperature. Deuterium
remained at 2-position of the resulted benzofuran 18D and
also in the recovered Z-isomer Z-1D as shown in Scheme
7. From these results, we could exclude the intermediacy
of allyl chloride and carbene, which is described later (see
Section 3.1).
(R3=(CH2)2Ph)
Scheme 6. Preparation of bromoalkene with homoallylic thiol. Reagents
and conditions: (a) AcSH, DIAD, PPh3, THF, rt, 32% (12a), 50% (E-
12d), 46% (Z-12d). (b) KOH, MeOH, rt, 79% (13a), 91% (E-13d), 76%
(Z-13d). (c) Br2, CCl4, rt, then KOH, MeOH, rt, 66%. (d) AcSH, DIAD,
PPh3, THF, rt, 30%. (e) K2CO3, MeOH, rt, 65%. Ac¼acetyl; DIAD¼diiso-
propyl azodicarboxylate.
2.3. Cyclization of sulfonamides
Table 1. Cyclization reaction of haloalkenes having a hydroxy groupa
Some tosylamides having E-haloalkenyl moieties were sub-
jected to the cyclization and the results are listed in Table 2.
Homoallylic amide 7a having an alkyl group at the a-posi-
tion was treated with various bases in 1,3-dimethyl-2-imid-
azolidinone (DMI), which was used instead of DMF to
ensure the reaction at higher temperature. When sodium
hydride was used as a base, dihydropyrrole 20a was obtained
in 76% yield within an hour (entry 1). The treatment with so-
dium methoxide or potassium carbonate also gave the prod-
uct in good yield, although the reaction became slower
(entries 2 and 3). Compound 7b having a phenyl group at
the a-position gave the corresponding product 20b at
100 ꢁC in 77% yield (entry 4). The treatment of tosylamides
having no a-substituent (7c and 7d) with sodium hydride
also gave the cyclization products in good yield (entries 5
and 6). N-Tosylanilide 10 was smoothly converted to the cor-
responding N-tosylindole 21 at lower temperature (80 ꢁC) by
the treatment of various bases (NaH, NaOMe, and K2CO3),
in which potassium carbonate gave the best yield of the prod-
uct (entry 9).
Entry Starting material
Product
Me
Temp/ꢁC Time/h Yield/%
Me
Cl
1
rt
13
95
O
OH
E-1
18
Me
2
18
rt to 110b 16b
0 (100)c
Cl
OH
Z-1
Me
Br
3
18
rt
rt
3
73
OH
E-2
Me
4
18
144
6 (87)c
Br
OH
Z-2
As mentioned above, E-bromohomoallylsulfonamides
smoothly cyclized to dihydroindole derivatives, whereas
the corresponding Z-sulfonamide Z-7a was found to give
only 4% yield of the cyclized product even after longer
heating. The Z-isomer of N-tosylanilide 10, Z-10 gave no
cyclization product even after heating at 120 ꢁC for 6 h
and was recovered in 95% (Scheme 8).
Cl
O
OH
H
Ph
5
6
80
80
10
10
82
Ph
H
19
E-3
Cl
H
OH
19
0d
Ph
2.4. Cyclization of active methine compounds
Z-3
The formation of carbocycles was then examined by using
active methine compounds 11c and 11d having cyano and
phenylsulfonyl groups (Table 3). As compared to the cycli-
zation of sulfonamides, it took longer time to consume the
a
b
c
d
Reactions were carried out in DMF with 1.5 equiv of NaH.
rt, 13 h; 50 ꢁC, 1 h; 80 ꢁC, 1 h; 110 ꢁC, 1 h.
Recovery of the starting material.
A complex mixture.
Me
Cl
Me
Me
D
1.5 mol amt. NaH
DMF, rt, 13 h
+
D
D
Cl
O
OH
1D
OH
18D
(78% from E, 91% D)
Z-1D
(E/Z = 2.5:1, 93% D)
(98% recovery, 93% D)
Scheme 7. Reaction of deuterated chloroalkene.

H. Miyauchi et al. / Tetrahedron 63 (2007) 5940–5953
Table 2. Cyclization reaction of bromoalkenes having tosylamide moietya
5943
Entry
Starting material
Product
Base
Temp/ꢁC
Time/h
1
Yield/%
76
Ts
N
Br
Me
Ts
HN
1
NaH
120
(CH2)2Ph
(CH2)2Ph
Me
7a
20a
20a
20a
2
3
7a
7a
NaOMe
K2CO3
120
120
5
5
87 (10)b
80 (15)b
Ts
N
Br
Ts
HN
Ph
4
5
6
NaH
NaH
NaH
100
120
120
1.5
5
77 (10)b
Me
Ph
Ts
Me
7b
20b
Ts
N
Br
HN
87
Me
Me
7c
20c
Ts
N
Br
Ph(CH2)2
Ts
HN
5
69 (18)b
Ph(CH2)2
20d
7d
Me
Me
Cl
7
NaH
80
2
77
N
Ts
NH
Ts
21
10
8
9
10
10
21
21
NaOMe
K2CO3
80
80
3
3
87
89
a
Reactions were carried out in DMI with 1.5 equiv of base.
Recovery of the starting material.
b
Table 3. Cyclization reaction of bromoalkenes with an active methane
Ts
N
Br
HN
Ts
moietya
1.5 mol amt. NaH
DMI, 120 ºC, 18 h
(CH2)2Ph
Entry
Starting material
Product
Base
Time/ Yield/
h
Me
(CH2)2Ph
Me
%
Z-7a
20a 4%
(Z-7a recovery 70%)
NC
SO2Ph
Br
Me
CN
SO2Ph
1
2
NaH 10
NaOMe 12
61
71
Me
Me
Me
E-11c
22c
NC
1.5 mol amt. K2CO3
SO2Ph
Cl
N
Br
CN
DMI, 80 ºC, 3 h
120 ºC, 6 h
NH
Ts
Ts
SO2Ph
3
NaOMe 12
50
0
21 0%
Ph(CH2)2
Ph(CH2)2
Z-10
(Z-10 recovery 95%)
E-11d
22d
Scheme 8. Reactions of Z-isomers.
Br CN
SO2Ph
starting materials, presumably due to the steric hindrance.
From E-11c, cyclopentene 22c was obtained in a moderate
yield (entries 1 and 2). Each of E/Z-isomers of bromoalkene
11d was treated independently under the same conditions.
Although the E-isomer E-11d was converted to cyclo-
pentene 22d in 50% yield (entry 3), the Z-isomer Z-11d
was recovered in 34% and no cyclized products were
detected (entry 4). Thus the cyclization with active methine
moiety also revealed to proceed in a stereospecific manner.
The moderate yield of the products 22 may originate from
the instability of the products under basic conditions.
4
a
22d
NaOMe 12
(34)b
Ph(CH2)2
Z-11d
Reactions were carried out in DMI with 1.5 equiv of base at 102 ꢁC.
Recovery of the starting material.
b
E/Z-mixture (10:1) of thiol 13a was treated with NaH in
DMI, the reaction proceeded even at room temperature,
giving dihydrothiophene 23a in 70% yield (entry 1). Inter-
estingly, in contrast to the previous cyclization of alcohols,
amides, and active methine derivatives, the Z-isomer was
not recovered. This meant that the both stereoisomers could
be cyclized to 23a. To confirm this, each of the E- and
Z-isomer of bromoalkenes 13d was treated with sodium
hydride. The same cyclopentene 23d was obtained in 34%
2.5. Cyclization of thiols
The cyclization of thiols to dihydrothiophene was found to
proceed very smoothly as shown in Table 4. When an

5944
H. Miyauchi et al. / Tetrahedron 63 (2007) 5940–5953
Table 4. Cyclization reaction of bromoalkenes with a thiol moietya
3.1. Mechanistic possibilities
Entry
Starting material
Product
Temp/ Time/ Yield/
ꢁC
As mentioned before, vinylic substitution has many mecha-
nistic possibilities. Besides the addition–elimination, SNVs,
and SNVp reaction mechanisms,20 the allylic isomerization
and the vinyl carbene formation may be the candidates for
the reaction mechanism (Scheme 10).
h
%
Br
Me
S
SH
(CH2)2Ph
(CH2)2Ph
1
rt
9
70
Me
13a (E/Z = 10:1)
23a
Br
S
SH
Nu
Br
Br
Me
Br
H
H
Nu
Nu
2
50
80
6
4
34
12
Nu
Ph(CH2)2
E-13d
Ph(CH2)2
23d
Br
H
H
SH
Nu
Nu
3
23d
Ph(CH2)2
Z-13d
Me
Me
Me
Scheme 10. Allylic isomerization and carbene insertion.
a
Reactions were carried out in DMI with 1.5 equiv NaH.
The stereospecificity observed in the cyclization of alcohols,
amides, and active methyne derivative nucleophiles can
deny both the allylic isomerization and the carbene forma-
tion,21 because these reactions can proceed from both
E- and Z-isomers. Furthermore, the deuterium-label ex-
periment depicted in Scheme 7 clearly shows the vinylic
hydrogen remains intact during the reaction. Accordingly,
we discuss here the addition–elimination, SNVs, and
SNVp reactions only.
and 12% yields, respectively (entries 2 and 3). It is quite
noteworthy that the cyclization reaction proceeded from
the both isomers.
In addition to the ring closure to five-membered dihydrothio-
phenes, the formation of four-membered ring was examined
(Scheme 9). When thiol 17 was treated with potassium
carbonate in DMI at 120 ꢁC, methylenethietane 24 was
obtained in 78% yield. The reaction of the corresponding
bromohomoallyl alcohol did not give a cyclized product
(oxetane) but an allene derivative as a dehydrobromination
product. The analogous reaction of tosylamide to give azeti-
dine did not proceed and resulted in the recovery of the tosyl-
amide.
3.2. Cyclization of alcohols
We have already reported the transition structures for the
cyclization of the anion E-25 both in the gas phase and in
DMF.9 The in-plane SN2-type structures E-25-ts were ob-
tained with the activation energy of 17.1 kcal molꢀ1 in the
gas phase and 14.4 kcal molꢀ1 in DMF (Fig. 1a). On the
other hand, Z-25 gave the SNVp transition structure Z-25-ts
with the activation energy of 28.9 kcal molꢀ1 (Fig. 1b). The
larger activation energy compared to the SNVs reaction is
Me
Me
SH
Me
Br
1.5 mol amt. K2CO3
DMI, 120 ºC, 1.5 h
Me
S
Ph(CH2)2
Ph(CH2)2
17
Scheme 9. Formation of thietane.
24 78%
3. Theoretical study
In order to examine the reaction mechanisms, theoretical
calculations were done by using Gaussian program.15 All
calculations were performed at the B3LYP16/6-31+G(d)
level and the solvent effect was included by using the Ons-
ager continuum model17 for DMF (3¼37.06) as a solvent.
DMI has an almost 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. Vibrational frequency calculations gave only one
imaginary frequency for all transition structures and only
harmonic frequencies for the reactants and products. The
structures of the reactants and products were obtained by
the optimization of the last structures on both sides of IRC
(intrinsic reaction coordinate) calculations.18 Gibbs free
energies are calculated at 298.15 K and 1.00 atm. The ther-
mal energy corrections are not scaled, because the scale fac-
tors for B3LYP are very close to 1.0.19
Figure 1. Transition structures for the nucleophilic cyclization of phen-
oxides 25 [B3LYP/6-31+G(d), SCRF (dipole, solv¼DMF)]. Selected bond
˚
lengths are shown in A. The italic numbers are the values in the gas phase.

H. Miyauchi et al. / Tetrahedron 63 (2007) 5940–5953
5945
gas phase (14.3 kcal molꢀ1). This difference seems to arise
from the large stabilization of the unstable oxyanion in a
polar solvent. Z-Isomer Z-26 gave the SNVp transition struc-
ture Z-26-ts contrastively (Fig. 2b) and the activation energy
in DMF is estimated as 30.8 kcal molꢀ1, which is also higher
than that in the gas phase (21.8 kcal molꢀ1).
3.3. Cyclization of tosylamides
The DFT calculations on the cyclization of the anion E-27c
derived from E-isomer E-7c gave the SNVs type transition
structure E-27c-ts (Fig. 3a). The nitrogen approached the
alkenyl bromide from the backside of the C–Br bond in
the plane of the vinylic carbons. The distances of the forming
˚
N–C and the breaking C–Br bonds were 2.35 and 2.49 A,
respectively. The length of the C]C double bond was
slightly decreased in the transition state, which suggests
that the central vinylic carbon has been changed from the
sp2 hybridization into an sp-like state due to the interaction
of the nucleophile with the s* orbital of the C–Br bond. The
reaction gave a loose complex of dihydropyrrole 19c and
bromide ion without the formation of any intermediates.
The reaction was exothermic and the heat of reaction in
the gas phase was estimated as 27.4 kcal molꢀ1. The acti-
vation energies for the transition state were estimated as
26.1 kcal molꢀ1 in the gas phase and 20.5 kcal molꢀ1 in
DMF. In the Onsager reaction field, the reactant E-27c was
stabilized by 5.1 kcal molꢀ1 as compared with the gas phase
energy, while the transition state E-27c-ts was stabilized by
10.7 kcal molꢀ1. Several attempts to obtain an SNVp type
transition state from the E-isomer failed.
Figure 2. Transition structures for the nucleophilic cyclization of alkoxides
26 [B3LYP/6-31+G(d), SCRF (dipole, solv¼DMF)]. Selected bond lengths
˚
are shown in A. The italic numbers are the values in the gas phase.
consistent with the experimental failure of the cyclization of
Z-1.
The cyclization of the anion 26 was also studied. E-Isomer
E-26 gave the SNVs transition state E-26-ts with the activa-
tion energy of 18.1 kcal molꢀ1 in DMF (Fig. 2a). It is note-
worthy that the activation energy is higher than that in the
Figure 3. Transition structures for the nucleophilic cyclization of tosylamidates 27 [B3LYP/6-31+G(d), SCRF (dipole, solv¼DMF)]. Selected bond lengths are
˚
shown in A. The italic numbers are the values in the gas phase.

5946
H. Miyauchi et al. / Tetrahedron 63 (2007) 5940–5953
On the contrary, the anion Z-27c derived from Z-7c gave
only the SNVp type transition structure Z-27c-ts (Fig. 3b).
The length of the C]C double bond in the transition state
was slightly increased due to the interaction with the p*
orbital. It resembles the addition–elimination pathway, but
the bond formation and cleavage were almost simultaneous.
The product was the same as that from the E-isomer E-27c
with the heat of reaction being 24.6 kcal molꢀ1 in the gas
phase. The activation energy of the SNVp reaction was
calculated as 34.3 kcal molꢀ1 both in the gas phase and in
DMF. The SCRF calculations did not change the activation
energy, because both the transition structure Z-27c-ts and
the reactant Z-27c were stabilized to the same extent
(5.6 kcal molꢀ1 compared to the gas phase energy). These
values of activation energy are much higher than those of
the SNVs reaction from the E-isomer E-27c and the results
are consistent with the experimental results, that is, Z-isomer
Z-7c gave only 4% yield of the product 20c.
3.4. Cyclization with carbanion
For the carbon nucleophiles, the reactant anions E-29c and
Z-29c derived from E-11c and Z-11c, respectively, were
placed in the gas phase and in the self-consistent reaction
field. In the same as the nitrogen nucleophiles, only the
SNVs type transition structure E-29c-ts was obtained from
the E-isomer E-29c, and the SNVp type Z-29c-ts from the
Z-isomer Z-29c (Fig. 5). The activation energies of the
SNVs type reaction from the E-isomer E-29c were
28.4 kcal molꢀ1 in the gas phase and 23.5 kcal molꢀ1 in
DMF, while those of the SNVp type reaction pathway
from the Z-isomer Z-29c were 33.2 kcal molꢀ1 in the gas
phase and 29.9 kcal molꢀ1 in DMF. Although both the acti-
vation energies of the SNVs and SNVp type reactions were
lowered in the SCRF method, the SNVs reaction still had
lower activation energies. These results are in good accor-
dance with the stereospecific formation of 22 from the E-iso-
mer in the experiments. Furthermore, the higher activation
energy of E-29c-ts compared with E-27c-ts may reflect the
steric hindrance of the carbon nucleophile and can explain
the slow cyclization reaction of 8.
Similar results were obtained for the anion 28 derived from
phenylene-tethered compound 10. E-Isomer E-28 gave only
the SNVs type transition structure E-28-ts, which requires
the activation energies of 22.1 kcal molꢀ1 in the gas phase
and 15.3 kcal molꢀ1 in DMF (Fig. 4a). These values are
lower than those of E-27c-ts and are in accordance with
the experimental results that the reaction proceeded at lower
temperature (80 ꢁC) compared with the dihydropyrrole
synthesis (7 to 20, 120 ꢁC). This is probably because the
phenylene tether can make reaction centers close to each
other. Z-Isomer Z-28 gave the SNVp type transition structure
Z-28-ts with the activation energies of 33.7 kcal molꢀ1 in the
gas phase and 33.5 kcal molꢀ1 with solvent effect (Fig. 4b).
Again, the SCRF model did stabilize the SNVp transition
state Z-28-ts as the same extent as the reactant Z-28.
3.5. Cyclization of thiols
For the cyclization of thiol, E-anion E-30a generated from
E-13a gave the SNVs transition structure E-30a-ts
(Fig. 6a). The activation energy is 19.6 kcal molꢀ1 in the
gas phase. The calculation with SCRF method gave the
activation energy of 12.5 kcal molꢀ1, which is reasonably
in agreement with the room temperature reaction of 13a
(E/Z¼10:1). Several attempts to obtain SNVp transition
structure from E-30a were unsuccessful. On the other
hand, the SNVp type transition structure Z-30a-ts was
Figure 4. Transition structures for the nucleophilic cyclization of tosylanilidates 28 [B3LYP/6-31+G(d), SCRF (dipole, solv¼DMF)]. Selected bond lengths are
˚
shown in A. The italic numbers are the values in the gas phase.

H. Miyauchi et al. / Tetrahedron 63 (2007) 5940–5953
5947
Figure 5. Transition structures for the nucleophilic cyclization of carbanions 29c [B3LYP/6-31+G(d), SCRF (dipole, solv¼DMF)]. Selected bond lengths are
˚
shown in A. The italic numbers are the values in the gas phase.
Figure 6. Transition structures for the nucleophilic cyclization of thiolate anions 30a [B3LYP/6-31+G(d), SCRF (dipole, solv¼DMF)]. Selected bond lengths
˚
are shown in A. The italic numbers are the values in the gas phase.
obtained from Z-isomer Z-30a and its activation energies are
20.6 kcal molꢀ1 in the gas phase and 20.0 kcal molꢀ1 in
DMF, respectively (Fig. 6b). Since the activation energy of
the SNVp reaction is smaller than that of the nitrogen
(E-27c-ts, 20.5 kcal molꢀ1) and the carbon (E-29c-ts,
23.4 kcal molꢀ1) nucleophiles, the cyclization reaction of
Z-13a could also occur. The experimental results obtained
from 13a and 13d accord with these calculation results
although the yields are low.
The transition state structure for the thietane formation from
thiol 17 was also studied and only the SNVp type transition
structure 31-ts was obtained instead of the SNVs type
(Fig. 7). The activation energy for 31-ts was 20.0 kcal molꢀ1
Figure 7. A transition structure for the nucleophilic cyclization of thiolate
31 [B3LYP/6-31+G(d), SCRF (dipole, solv¼DMF)]. Selected bond lengths
˚
are shown in A. The italic numbers are the values in the gas phase.

5948
H. Miyauchi et al. / Tetrahedron 63 (2007) 5940–5953
in DMF. Due to the large steric expulsion between the
thiolate and the isopropylidene group, the SNVs reaction
became unfavorable. In fact, both the SNVs and the SNVp
transition structures were obtained in the case of the thiolate
without the two methyl groups, and they have almost the
same activation energies (24.7 kcal molꢀ1 for SNVs and
24.9 kcal molꢀ1 for SNVp) in the gas phase.
To an ice-cold solution of tetramethylethylenediamine
(8 mL, 53 mmol) in Et2O (30 mL) was added n-BuLi
(40 mmol), and the solution was stirred at room temperature
for 1 h. The solution was then cooled (0 ꢁC), and 3-methyl-
3-buten-1-ol (2 mL, 20 mmol) was added slowly. The result-
ing solution was stirred for 6 h at room temperature to give
a heterogeneous dark yellow suspension. The slurry was
cooled to ꢀ78 ꢁC and benzyl bromide (1.2 mL, 10 mmol)
in Et2O (5 mL) was added dropwise. The reaction vessel
was allowed to warm up to room temperature and stirred
for 6 h. The reaction was quenched with satd NH4Cl aq
and diluted with H2O. Organic materials were extracted
three times by Et2O and combined organic layer was washed
successively with 1 M HCl and brine, dried over MgSO4,
and concentrated in vacuo. Purification by column chro-
matography (hexane/ethyl acetate 4:1 to 2:1 v/v, grad-
ient) gave 3-methylene-5-phenylpentan-1-ol (4d, 1.1 g,
6.5 mmol, 65%).
4. Conclusion
By the intramolecular vinylic substitution reaction, benzo-
furan, dihydrofuran, indole, dihydropyrrole, cyclopentene,
dihydrothiophene, and thietane derivatives were synthesized
from various vinylic halides, which have nucleophilic moie-
ties at the suitable positions. Among the possible reaction
mechanisms, fundamentally, the SNVs reaction pathway
was feasible for E-isomers and the SNVp pathway for
Z-isomers. The theoretically predicted activation energies
of SNVs reactions were generally smaller than those of
SNVp reactions, although the activation energies for the
SNVp reactions of thiols were relatively small, which
make the SNVp pathway also possible.
Colorless oil; 1H NMR (500 MHz, CDCl3) d 7.30–7.27 (2H,
m), 7.20–7.18 (3H, m, overlapped), 4.92 (1H, distorted s),
4.87 (1H, distorted s), 3.72 (2H, t, J¼6.3 Hz), 2.77 (2H, t,
J¼8.1 Hz), 2.36–2.32 (4H, m, overlapped), 1.50 (1H, br);
13C NMR (125 MHz, CDCl3) d 145.4, 141.8, 128.3, 128.3,
125.9, 112.0, 60.3, 39.3, 37.5, 34.2; IR (ZnSe) 3338, 2935,
1645, 1603, 1496, 1454, 1041, 891, 744, 696 cmꢀ1. Found:
C, 81.62; H, 9.23%. Calcd for C12H16O: C, 81.77; H,
9.15%.
5. Experimental
5.1. General
1H and 13C NMR spectra were recorded on Bruker DRX500
and AVANCE 500 spectrometers at 500 and 125 MHz,
respectively. Chemical shifts were reported in parts per mil-
lion relative to trimethylsilane (internal standards, d¼0, for
1H) and solvent peaks (d¼77.0, for 13C). Multiplicities are
abbreviated as follows: s¼singlet, d¼doublet, t¼triplet,
q¼quartet, m¼multiplet, br ¼broad. Infrared spectra were
obtained on a Horiba FT-300S spectrometer. High-resolu-
tion mass spectra were measured on a JEOL JMS-700P
using FAB ionization with m-nitrobenzylalcohol (NBA) as
a matrix. Elemental analyses were performed at The
Elemental Analysis Laboratory, Department of Chemistry,
Faculty of Science, The University of Tokyo. All melting
points are uncorrected. Flash column chromatography was
carried out with PSQ100B silica gel (spherical, neutral,
Fuji Silicia Kagaku). Preparative thin layer chromatography
(PTLC) was performed on Wakogel B-5F silica gel (Wako
Pure Chemical Industries, Ltd.). Dehydrated Et2O, THF,
and CH2Cl2 were purchased from Kanto Chemical Co.,
Inc., and were dried and degassed by Glass Contour solvent
dispenser system. MeOH was distilled from a small amount
5.2.2. Typical procedure for the preparation of bromo-
alkenes with alcohol moiety. 4-Bromo-3-methylbut-3-en-
1-ol (5c) was prepared as described in the literature,10 and
E/Z-isomers were separated by column chromatography.
Other bromoalkenyl alcohols were synthesized in a similar
procedure from corresponding alkenyl alcohols.
To a stirred solution of 5-methyl-1-phenylhex-5-en-3-ol 4a
(3.6 g, 19.0 mmol) in CCl4 (100 mL) was added a solution
of bromine (3.2 g, 20.0 mmol) in CCl4 (30 mL) at 0 ꢁC.
The resulting solution was stirred for 1 h, and the solvent
and excess bromine were removed in vacuo. The residual
brown oil was treated with 5 M solution of KOH in MeOH
(5 mL) at room temperature for 3 h. The reaction mixture
was quenched with water, 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 column chromatography (hexane/ethyl
acetate 5:1 v/v) to give an E/Z-mixture (10:1) of 5a (2.0 g,
7.6 mmol, 40%).
˚
of iodine and magnesium, and stored over MS 3 A. Dimethyl-
imidazolidinone was purchased from Aldrich Co., Inc., dis-
˚
tilled over CaH2, and stored under argon over MS 4 A. All
reactions were carried out under an argon atmosphere.
5.2.2.1.
6-Bromo-5-methyl-1-phenylhex-5-en-3-ol
(5a). The starting material 5-methyl-1-phenylhex-5-en-3-ol
(4a) was synthesized from 2-methylallylmagnesium chlo-
ride and 3-phenylpropanal.
5.2. Preparation of starting materials
Pale yellow oil; 10:1 mixture, data for the major isomer (E):
1H NMR (500 MHz, CDCl3) d 7.30–7.27 (2H, m), 7.22–7.18
(3H, m, overlapped), 6.00 (1H, s), 3.77–3.72 (1H, m), 2.84–
2.79 (1H, m), 2.72–2.66 (1H, m), 2.31–2.27 (1H, m), 2.26–
2.22 (1H, m), 1.83–1.74 (2H, m, overlapped), 1.80 (3H, s),
1.60 (1H, br); 13C NMR (125 MHz, CDCl3) d 141.7,
138.6, 128.4, 128.4, 125.9, 103.7, 68.1, 46.4, 38.6, 32.0,
19.3; IR (ZnSe) 3388, 2935, 1630, 1603, 1495, 1454,
Preparation of compounds 1, 2, and 3 is described in the pre-
ceded literature.9
5.2.1. 3-Methylene-5-phenylpentan-1-ol (4d). This com-
pound was prepared by using 3-methyl-3-buten-1-ol dianion
chemistry described by Chong et al.22

H. Miyauchi et al. / Tetrahedron 63 (2007) 5940–5953
5949
1288, 1163, 1053, 698 cmꢀ1. Found: C, 57.86; H, 6.46%.
Calcd for C13H17BrO: C, 58.01; H, 6.37%.
To an ice-cold solution of 6-bromo-5-methyl-1-phenyl-
hex-5-en-3-ol (5a, 97 mg, 0.36 mmol), PPh3 (0.19 g,
0.72 mmol), and N-butoxycarbonyltosylamide (0.15 g,
0.55 mmol) in THF (10 mL) was added dropwise a toluene
solution of diethyl azodicarboxylate (40 wt %, ca. 2.2 M,
0.25 mL, 0.54 mmol). The resulting mixture was stirred
for 12 h at room temperature and solvents were evaporated
under reduced pressure. Residual materials were treated
with Et2O and insoluble compounds were filtered. Filtrate
was concentrated in vacuo and subjected to column chroma-
tography (hexane/ethyl acetate 5:1 v/v) to give E-6a (84 mg,
0.16 mmol, 44%), Z-6a (10 mg, 0.02 mmol, 6%), and 5a
(26 mg, 0.10 mmol, 27%). E/Z-Isomers of 6b were also
separated at this step.
5.2.2.2.
4-Bromo-3-methyl-1-phenylbut-3-en-1-ol
(5b). This compound was synthesized from 3-methyl-1-phe-
nylbut-3-en-1-ol (4b), which was prepared from 2-methyl-
allylmagnesium chloride and benzaldehyde.
1
Colorless oil; 7:1 mixture, data for major isomer (E): H
NMR (500 MHz, CDCl3) d 7.37–7.22 (5H, m, overlapped),
5.95 (1H, s), 4.73 (1H, dd, J¼8.7, 4.2 Hz), 2.49 (1H, dd,
J¼14.0, 8.7 Hz), 2.40 (1H, dd, J¼14.0, 4.2 Hz), 2.36 (1H,
br), 1.82 (3H,s); 13C NMR (125 MHz, CDCl3) d 143.5,
138.2, 128.4, 127.7, 125.6, 104.2, 71.6, 48.0, 19.3; IR
(ZnSe) 3392, 2912, 1630, 1492, 1454, 1286, 1161, 1049,
1026, 756, 696, 532 cmꢀ1. Found: C, 54.56; H, 5.57%.
Calcd for C11H13BrO: C, 54.79; H, 5.43%.
E-6a (61 mg, 0.12 mmol) was dissolved in CH2Cl2 (5 mL)
and treated with CF3COOH (0.09 mL, 0.13 g, 1.17 mmol)
at room temperature overnight. The reaction mixture
was quenched with NaHCO3 aq and extracted three
times with Et2O. The extracts were washed with brine,
dried over MgSO4, and concentrated in vacuo. The crude
product was purified by PTLC (hexane/ethyl acetate 3:1
v/v) to give E-7a (45 mg, 0.11 mmol, 92%). Contaminant
Z-isomers could be removed by recrystalization (hexane/
CH2Cl2).
5.2.2.3. (E)-3-(Bromomethylene)-5-phenylpentan-1-ol
(E-5d). E/Z-Isomers of 5d were separable.
Colorless oil; 1H NMR (500 MHz, CDCl3) d 7.31–7.28 (2H,
m), 7.24–7.19 (3H, m, overlapped), 6.05 (1H, s), 3.69 (2H, t,
J¼6.3 Hz), 2.76 (2H, t, J¼8.2 Hz), 2.52 (2H, t, J¼8.2 Hz),
2.34 (2H, t, J¼6.3 Hz), 1.63 (1H, br); 13C NMR
(125 MHz, CDCl3) d 141.5, 141.2, 128.4, 128.3, 126.1,
104.0, 60.1, 39.3, 34.8, 33.2; IR (ZnSe) 3354, 2929, 1624,
1603, 1495, 1454, 1038, 746, 696, 563 cmꢀ1. Found: C,
56.44; H, 6.07%. Calcd for C12H15BrO: C, 56.49; H,
5.93%.
5.2.3.1. (E)-N-(6-Bromo-5-methyl-1-phenylhex-5-en-
3-yl)-4-methylbenzenesulfonamide (E-7a). White powder;
mp 113 ꢁC; 1H NMR (500 MHz, CDCl3) d 7.69 (2H, d, J¼
8.3 Hz), 7.29 (2H, d, J¼8.3 Hz), 7.26 (2H, dd, J¼7.5,
7.3 Hz), 7.19 (1H, t, J¼7.3 Hz), 7.05 (2H, d, J¼7.5 Hz),
5.85 (1H, s), 4.51 (1H, br), 3.33–3.25 (1H, m), 2.63–2.50
(2H, m), 2.43 (3H, s), 2.20 (1H, dd, J¼13.8, 6.5 Hz), 2.14
(1H, dd, J¼13.8, 7.4 Hz), 1.82–1.68 (2H, m), 1.40 (3H, s);
13C NMR (125 MHz, CDCl3) d 143.5, 140.9, 137.8, 137.4,
129.7, 128.4, 128.3, 127.2, 126.0, 104.4, 51.0, 43.9, 36.6,
31.4, 21.5, 18.6; IR (ZnSe) 3278, 2924, 1599, 1495, 1456,
5.2.2.4. (Z)-3-(Bromomethylene)-5-phenylpentan-1-ol
(Z-5d). Colorless oil; H NMR (500 MHz, CDCl3) d 7.29
1
(2H, dd, J¼7.5, 7.4 Hz), 7.20 (1H, t, J¼7.4 Hz), 7.16 (2H,
d, J¼7.5 Hz), 6.03 (1H, s), 3.78 (2H, t, J¼6.9 Hz), 2.75
(2H, t, J¼8.0 Hz), 2.57 (2H, t, J¼6.9 Hz), 2.45 (2H, t,
J¼8.0 Hz), 1.53 (1H, br); 13C NMR (125 MHz, CDCl3)
d 141.6, 140.9, 128.4, 128.3, 126.1, 104.1, 60.3, 38.3,
36.1, 34.2; IR (ZnSe) 3342, 2943, 1624, 1603, 1496, 1454,
1041, 746, 698, 561 cmꢀ1. Found: C, 56.51; H, 6.06%.
Calcd for C12H15BrO: C, 56.49; H, 5.93%.
1325, 1157, 1092, 920, 814, 771, 700, 665, 550 cmꢀ1
.
Found: C, 56.76; H, 5.85; N, 3.14%. Calcd for
C20H24BrNO2S: C, 56.87; H, 5.73; N, 3.32%.
5.2.3.2. (Z)-N-(6-Bromo-5-methyl-1-phenylhex-5-en-
3-yl)-4-methylbenzenesulfonamide (Z-7a). Colorless oil;
1H NMR (500 MHz, CDCl3) d 7.72 (2H, d, J¼8.2 Hz),
7.28–7.24 (4H, m, overlapped), 7.18 (1H, t, J¼7.4 Hz),
7.07 (2H, d, J¼7.0 Hz), 5.78 (1H, q, J¼1.3 Hz), 4.59 (1H,
br), 3.50–3.42 (1H, m), 2.69–2.63 (1H, m), 2.60–2.54
(1H, m), 2.42 (3H, s), 2.38 (1H, dd, J¼13.6, 8.4 Hz), 2.26
(1H, dd, J¼13.6, 6.5 Hz), 1.84–1.72 (2H, m, overlapped),
1.47 (3H, d, J¼1.3 Hz); 13C NMR (125 MHz, CDCl3)
d 143.3, 141.1, 137.9, 137.7, 129.5, 128.4, 128.3, 127.2,
125.9, 103.9, 51.9, 39.5, 37.0, 31.5, 22.0, 21.5; IR (ZnSe)
3275, 2922, 1599, 1495, 1452, 1323, 1157, 1090, 916,
5.2.2.5.
5-Bromo-6-methyl-1-phenylhept-5-en-3-ol
(15). This compound was derived from 6-methyl-1-phenyl-
hept-5-en-3-ol (14), which was prepared according to the
literature.23
Colorless oil; 1H NMR (500 MHz, CDCl3) d 7.29–7.27 (2H,
m), 7.22–7.17 (3H, m, overlapped), 4.03–3.97 (1H, m),
2.87–2.78 (2H, m, overlapped), 2.72–2.66 (1H, m), 2.55–
2.51 (1H, m), 1.90 (3H, s), 1.85–1.79 (2H, m, overlapped),
1.81 (3H, s), 1.75 (1H, br); 13C NMR (125 MHz, CDCl3)
d 141.9, 133.8, 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
(FAB+) Found: 283.0693. Calcd for C14H20BrO (M+H+):
283.0698.
814, 700, 663, 550 cmꢀ1
.
HRMS (FAB+) Found:
422.0779. Calcd for C20H25BrNO2S (M+H+): 422.0789.
5.2.3.3.
(E)-N-(4-Bromo-3-methyl-1-phenylbut-3-
enyl)-4-methylbenzenesulfonamide (E-7b). White pow-
der; mp 81 ꢁC; 1H NMR (500 MHz, CDCl3) d 7.55 (2H, d,
J¼8.3 Hz), 7.17–7.14 (3H, m, overlapped), 7.16 (2H, d,
J¼8.3 Hz), 7.08–7.06 (2H, m), 5.88 (1H, s), 5.30 (1H, br),
4.37 (1H, dd, J¼8.8, 6.3 Hz), 2.49 (1H, dd, J¼14.1,
8.8 Hz), 2.40 (1H, dd, J¼14.1, 6.3 Hz), 2.37 (3H, s), 1.55
5.2.3. Typical procedure for the preparation of bromo-
alkenes with tosylamide moiety. Compounds 7a and 7b
were prepared from an E/Z-mixture of 5a and 5b, respec-
tively, where E-7c and E-7d were derived from isolated
E-isomers of 5c and 5d, respectively.

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H. Miyauchi et al. / Tetrahedron 63 (2007) 5940–5953
(3H, s); 13C NMR (125 MHz, CDCl3) d 143.1, 140.3, 137.2,
137.0, 129.4, 128.5, 127.5, 127.1, 126.3, 105.2, 55.7, 46.5,
21.4, 18.7; IR (ZnSe) 3276, 2920, 1599, 1456, 1321, 1155,
1092, 1065, 949, 812, 700, 667 cmꢀ1. Found: C, 54.80; H,
5.32; N, 3.37%. Calcd for C18H20BrNO2S: C, 54.83; H,
5.11; N, 3.55%.
5.2.4.1. (E)-N-(2-(1-Chloroprop-1-en-2-yl)phenyl)-4-
methylbenzenesulfonamide (E-10). White powder; mp
117 ꢁC; 1H NMR (500 MHz, CDCl3) d 7.63 (1H, d,
J¼8.5 Hz), 7.61 (2H, d, J¼8.3 Hz), 7.26–7.29 (1H, m),
7.24 (2H, d, J¼8.3 Hz), 7.07–7.10 (1H, m), 6.98 (1H, d,
J¼7.6 Hz), 6.50 (1H, s), 5.56 (1H, s), 2.39 (3H, s), 1.78
(3H, s); 13C NMR (125 MHz, CDCl3) d 144.1, 136.2,
135.4, 133.5, 132.8, 129.7, 129.0, 128.9, 127.1, 125.0,
121.7, 118.6, 21.5, 18.7; IR (ZnSe) 3271, 1597, 1491,
5.2.3.4. (E)-N-(4-Bromo-3-methylbut-3-enyl)-4-meth-
ylbenzenesulfonamide (E-7c). White powder; mp 74 ꢁC;
1H NMR (500 MHz, CDCl3) d 7.74 (2H, d, J¼7.9 Hz),
7.33 (2H, d, J¼7.9 Hz), 5.88 (1H, q, J¼1.2 Hz), 4.36 (1H,
d, J¼6.1 Hz), 3.06 (2H, dt, J¼6.1, 6.2 Hz), 2.44 (3H, s),
2.26 (2H, t, J¼6.2 Hz), 1.67 (3H, d, J¼1.2 Hz); 13C NMR
(125 MHz, CDCl3) d 143.6, 137.6, 136.8, 129.8, 127.1,
104.1, 40.4, 38.0, 21.5, 18.5; IR (ZnSe) 3278, 2920, 1633,
1398, 1336, 1159, 1092, 912, 812, 758, 663, 543 cmꢀ1
.
Found: C, 59.64; H, 5.28; N, 4.16%. Calcd for
C16H16ClNO2S: C, 59.71; H, 5.01; N, 4.35%.
5.2.4.2. (Z)-N-(2-(1-Chloroprop-1-en-2-yl)phenyl)-4-
methylbenzenesulfonamide (Z-10). White powder; mp
88 ꢁC; 1H NMR (500 MHz, CDCl3) d 7.67 (2H, d,
J¼8.2 Hz), 7.58 (1H, d, J¼8.2 Hz), 7.29–7.26 (1H, m),
7.22 (2H, d, J¼8.2 Hz), 7.15–7.12 (1H, m), 6.98 (1H, d,
J¼7.6 Hz), 6.54 (1H, s), 6.18 (1H, s), 2.37 (3H, s), 1.64
(3H, s); 13C NMR (125 MHz, CDCl3) d 143.9, 136.6,
135.9, 132.7, 130.8, 129.6, 128.8, 128.0, 127.3, 125.1,
121.3, 116.3, 23.0, 21.5; IR (ZnSe) 3278, 1599, 1491,
1599, 1423, 1321, 1153, 1093, 912, 814, 660, 548 cmꢀ1
.
Found: C, 45.00; H, 5.10; N, 4.22%. Calcd for
C12H16BrNO2S: C, 45.29; H, 5.07; N, 4.40%.
5.2.3.5. (E)-N-(3-(Bromomethylene)-5-phenylpentyl)-
4-methylbenzenesulfonamide (E-7d). White powder; mp
72 ꢁC; 1H NMR (500 MHz, CDCl3) d 7.73 (2H, d,
J¼8.2 Hz), 7.31 (2H, d, J¼8.2 Hz), 7.28 (2H, dd, J¼7.4,
7.3 Hz), 7.20 (1H, t, J¼7.4 Hz), 7.14 (2H, d, J¼7.3 Hz),
5.92 (1H, s), 4.30 (1H, d, J¼6.6 Hz), 3.03 (2H, dt, J¼6.6,
6.6 Hz), 2.63 (2H, t, J¼8.2 Hz), 2.41 (3H, s), 2.35 (2H, t,
J¼8.2 Hz), 2.21 (2H, t, J¼6.6 Hz); 13C NMR (125 MHz,
CDCl3) d 143.7, 140.9, 140.8, 136.7, 129.8, 128.4, 128.3,
127.1, 126.2, 104.9, 40.6, 36.1, 34.2, 33.0, 21.5; IR (ZnSe)
3276, 2925, 1599, 1495, 1454, 1323, 1155, 1093, 814,
698, 661, 550 cmꢀ1. Found: C, 55.82; H, 5.58; N, 3.26%.
Calcd for C19H22BrNO2S: C, 55.88; H, 5.43; N, 3.43%.
1396, 1336, 1159, 1092, 914, 814, 758, 663, 555 cmꢀ1
.
Found: C, 59.53; H, 5.19; N, 4.20%. Calcd for
C16H16ClNO2S: C, 59.71; H, 5.01; N, 4.35%.
5.2.5. Typical procedure for the preparation of bromo-
alkenes with active methine moiety. A portion of azodi-
carbonyldipiperidine (0.35 g, 1.40 mmol) was added to
a mixture of (E)-3-(bromomethylene)-5-phenylpentan-1-ol
(E-5d, 0.16 g, 0.61 mmol), phenylsulfonylacetonitrile
(0.17 g, 0.92 mmol), and tributylphosphine (0.31 mL,
1.23 mmol) in THF (3 mL) at room temperature. After stir-
ring 6 h, the reaction mixture was passed through a Celite
pad, and collected solids were washed with Et2O. The filtrate
was concentrated under reduced pressure and purified by
column chromatography (hexane/ethyl acetate 5:1 v/v) to
give (E)-5-(bromomethylene)-7-phenyl-2-(phenylsulfonyl)-
heptanenitrile (E-11d, 0.10 g, 0.25 mmol, 41%).
5.2.4. The preparation of chloroalkenes with tosylanilide
moiety. To an ice-cold solution of diisopropylamine
(1.43 mL, 10.2 mmol) in THF (50 mL) was added a hexane
solution of n-BuLi (2.55 M, 4.0 mL, 10.2 mmol). After
stirring for 30 min at 0 ꢁC, the reaction mixture was cooled
to ꢀ78 ꢁC. Chloromethyltriphenylphosphonium chloride
(3.53 g, 10.2 mmol) was added and the solution was stirred
for 15 min at ꢀ78 ꢁC, 15 min at room temperature. The
reaction vessel was again cooled to ꢀ78 ꢁC and 2-amin-
acetophenone (0.5 mL, 0.56 g, 4.1 mmol) was added. The
resulting solution was allowed to warm up to room tem-
perature and stirred overnight. The reaction mixture was
quenched by a saturated NH4Cl solution, diluted with water,
and extracted three times with Et2O. The ethereal solution
was washed with brine, dried over MgSO4, and concentrated
under reduced pressure. Residual materials were isolated
with column chromatography to give E-9 (0.44 g,
2.6 mmol, 63%) and Z-9 (yield was not determined.). Minor
Z-isomer Z-9 was collected from several same reactions.
5.2.5.1.
(E)-5-(Bromomethylene)-7-phenyl-2-
(phenylsulfonyl)heptanenitrile (E-11d). Pale yellow oil;
1H NMR (500 MHz, CDCl3) d 8.01 (2H, d, J¼8.3 Hz),
7.79 (1H, t, J¼7.5 Hz), 7.66 (2H, dd, J¼8.3, 7.5 Hz),
7.31–7.29 (2H, m), 7.23–7.20 (3H, m, overlapped), 6.08
(1H, s), 3.82 (1H, dd, J¼10.9, 4.2 Hz), 2.77–2.72 (2H, m,
overlapped), 2.61–2.55 (1H, m), 2.46–2.40 (2H, m, overlap-
ped), 2.40–2.35 (1H, m), 2.28–2.23 (1H, m), 2.05–1.99 (1H,
m); 13C NMR (125 MHz, CDCl3) d 141.4, 140.7, 135.4,
135.4, 129.7, 129.6, 128.5, 128.3, 126.3, 113.5, 105.1,
56.5, 34.2, 33.1, 32.8, 24.6; IR (ZnSe) 2924, 1496, 1448,
1331, 1155, 1084, 785, 748, 725, 687, 600 cmꢀ1. HRMS
(FAB+) Found: 418.0475. Calcd for C20H21BrNO2S
(M+H+): 418.0476.
To a mixture of E-9 (0.44 g, 2.6 mmol), 4-dimethylamino-
pyridine (catalytic amount), and pyridine (0.63 mL, 0.62 g,
7.8 mmol) in CH2Cl2 (30 mL) was added tosyl chloride
(0.60 g, 3.1 mmol) at 0 ꢁC. After stirring overnight at
room temperature, the reaction was quenched with water,
extracted three times with CH2Cl2. The combined organic
layer was washed with brine, dried over MgSO4. CH2Cl2
was evaporated in vacuo, and the product E-10 (0.63 g,
75%) was isolated by column chromatography (hexane/
ethyl acetate 5:1 v/v).
5.2.5.2.
(Z)-5-(Bromomethylene)-7-phenyl-2-
(phenylsulfonyl)heptanenitrile (Z-11d). Pale yellow oil;
1H NMR (500 MHz, CDCl3) d 8.02 (2H, d, J¼8.6 Hz),
7.78 (1H, t, J¼7.5 Hz), 7.66 (2H, dd, J¼8.6, 7.5 Hz), 7.30
(2H, dd, J¼7.4, 7.0 Hz), 7.21 (1H, t, J¼7.4 Hz), 7.15 (2H,
d, J¼7.0 Hz), 6.05 (1H, s), 3.89 (1H, dd, J¼10.7, 4.1 Hz),
2.77–2.70 (2H, m, overlapped), 2.57–2.47 (2H, m, overlap-
ped), 2.43–2.35 (3H, m, overlapped), 2.11–2.03 (1H, m);

H. Miyauchi et al. / Tetrahedron 63 (2007) 5940–5953
5951
13C NMR (125 MHz, CDCl3) d 141.5, 140.4, 135.5, 135.4,
129.7, 129.6, 128.6, 128.3, 126.3, 113.8, 105.2, 56.9, 37.6,
34.1, 29.8, 24.3; IR (ZnSe) 2924, 1496, 1448, 1331, 1155,
1084, 789, 748, 725, 687, 598 cmꢀ1. HRMS (FAB+) Found:
418.0459. Calcd for C20H21BrNO2S (M+H+): 418.0476.
5.2.6.3. 6-Bromo-5-methyl-1-phenylhex-5-ene-3-thiol
(13a). Colorless oil; 10:1 mixture, data for the major isomer
(E): 1H NMR (500 MHz, CDCl3) d 7.31–7.28 (2H, m), 7.21–
7.18 (3H, m, overlapped), 5.99 (1H, s), 2.98–2.91 (1H, m),
2.89–2.83 (1H, m), 2.74–2.68 (1H, m), 2.46 (1H, dd,
J¼13.9, 6.2 Hz), 2.31 (1H, dd, J¼13.9, 8.4 Hz), 2.00–1.93
(1H, m), 1.76–1.67 (1H, m), 1.72 (3H, s), 1.50 (1H, d,
J¼5.8 Hz); 13C NMR (125 MHz, CDCl3) d 141.1, 138.8,
128.4, 128.4, 126.0, 104.0, 48.1, 39.5, 37.5, 33.2, 18.6; IR
(ZnSe) 2933, 1630, 1603, 1496, 1454, 1377, 1286, 1161,
1030, 748, 698 cmꢀ1. Found: C, 54.66; H, 5.87%. Calcd
for C13H17BrS: C, 54.74; H, 6.01%.
5.2.5.3. (E)-6-Bromo-5-methyl-2-(phenylsulfonyl)hex-
1
5-enenitrile (E-11c). White powder; mp 75 ꢁC; H NMR
(500 MHz, CDCl3) d 8.02 (2H, d, J¼8.1 Hz), 7.80 (1H, t,
J¼7.6 Hz), 7.67 (2H, dd, J¼8.1, 7.6 Hz), 6.06 (1H, s),
3.85–3.82 (1H, m), 2.49–2.45 (1H, m), 2.42–2.31 (2H, m,
overlapped), 2.08–2.01 (1H, m), 1.81 (3H, s); 13C NMR
(125 MHz, CDCl3) d 138.0, 135.4, 129.7, 129.6, 129.6,
113.6, 104.4, 56.4, 34.8, 24.5, 18.6; IR (ZnSe) 2922,
1633, 1583, 1448, 1331, 1155, 1084, 785, 750, 719, 687,
588 cmꢀ1. Found: C, 47.63; H, 4.47; N, 4.19%. Calcd for
C13H14BrNO2S: C, 47.57; H, 4.30; N, 4.27%.
5.2.6.4. 5-Bromo-6-methyl-1-phenylhept-5-ene-3-thiol
(18). Colorless oil; 1H NMR (500 MHz, CDCl3) d 7.30–7.27
(2H, m), 7.21–7.18 (3H, m, overlapped), 3.31–3.25 (1H, m),
2.92–2.86 (1H, m), 2.80 (1H, dd, J¼14.5, 8.2 Hz), 2.75–2.68
(2H, m, overlapped), 2.05–1.98 (1H, m), 1.91 (3H, s), 1.82
(3H, s), 1.79–1.71 (1H, m), 1.55 (1H, d, J¼5.9 Hz); 13C
NMR (125 MHz, CDCl3) d 141.4, 133.3, 128.4, 128.4,
125.9, 118.9, 46.7, 39.5, 38.8, 33.5, 25.5, 21.2; IR (ZnSe)
5.2.6. Typical procedure for the preparation of bromo-
alkenes with a thiol moiety. To a mixture of (E)-3-(bromo-
methylene)-5-phenylpentan-1-ol (E-5d, 0.15 g, 0.59 mmol)
and triphenylphosphine (0.23 g, 0.88 mmol) in THF (3 mL)
was added diisopropyl azodicarboxylate (0.17 mL,
0.88 mmol) over an ice bath. After 10 min, thioacetic acid
(0.06 mL, 0.88 mmol) was added and the resulting mixture
was stirred for 2 h. Hexanewas added to the reaction mixture,
which was then filtered, concentrated, purified by column
chromatography (hexane/ethyl acetate 10:1 v/v) to give
(E)-S-3-(bromomethylene)-5-phenylpentyl ethanethioate
(E-12d, 0.09 g, 0.30 mmol, 50%).
2914, 1655, 1603, 1496, 1454, 1221, 1012, 746, 698 cmꢀ1
.
Found: C, 56.38; H, 6.69%. Calcd for C14H19BrS: C,
56.19; H, 6.40%.
5.3. Typical procedure of the intramolecular vinylic
substitution reaction
(E)-N-(6-Bromo-5-methyl-1-phenylhex-5-en-3-yl)-4-methyl-
benzenesulfonamide (E-7a, 45 mg, 0.11 mmol) and NaH
(4 mg, 0.16 mmol) were dissolved in DMI (1 mL) and
heated at 120 ꢁC for 1 h. The reaction was quenched by
water and Et2O was added. The layers were separated and
the aqueous layer was extracted three times with Et2O.
The combined organic layer was washed several times
with water, then with brine, and dried over MgSO4. The
solvent was removed under reduced pressure and the crude
product was purified by PTLC using hexane/ethyl acetate
(5:1 v/v) as an eluent. 4-Methyl-2-phenethyl-1-tosyl-2,3-
dihydro-1H-pyrrole (20a, 28 mg, 0.08 mmol, 76%) was
obtained as colorless oil.
To a solution of E-12d (0.09 g, 0.30 mmol) in MeOH (3 mL)
was added K2CO3 (0.25 g, 1.80 mmol) at room temperature.
After 1 h, the reaction mixture was quenched by water,
acidified with 1 M HCl aq, and extracted three times with
Et2O. The combined organic layer was washed with brine,
dried over MgSO4, and evaporated in vacuo. Purification
on PTLC (hexane/ethyl acetate 10:1 v/v) gave (E)-3-(bromo-
methylene)-5-phenylpentane-1-thiol
0.27 mmol, 91%).
(E-13d,
0.07 g,
5.2.6.1. (E)-3-(Bromomethylene)-5-phenylpentane-1-
thiol (E-13d). Colorless oil; H NMR (500 MHz, CDCl3)
1
Spectral data of 4-methyl-1-tosyl-2,3-dihydro-1H-pyrrole
(20c)24 and 3-methyl-1-tosyl-1H-indole (21)25 were reported
and are in accordance with the data obtained in this work.
d 7.30 (2H, dd, J¼7.4, 7.4 Hz), 7.24–7.20 (3H, m, overlap-
ped), 6.03 (1H, s), 2.74 (2H, t, J¼8.2 Hz), 2.61 (2H, dt,
J¼7.6, 7.4 Hz), 2.49 (2H, t, J¼8.2 Hz), 2.39 (2H, t,
J¼7.4 Hz), 1.40 (1H, t, J¼7.6 Hz); 13C NMR (125 MHz,
CDCl3) d 142.4, 141.1, 128.4, 128.3, 126.1, 104.2, 40.5,
34.4, 33.2, 22.6; IR (ZnSe) 2929, 1622, 1603, 1495, 1454,
1271, 1076, 1030, 746, 696 cmꢀ1. HRMS (FAB+) Found:
271.0165. Calcd for C12H16BrS (M+H+): 271.0156.
5.3.1. 4-Methyl-2-phenethyl-1-tosyl-2,3-dihydro-1H-pyr-
role (20a). Colorless oil; 1H NMR (500 MHz, CDCl3) d 7.54
(2H, d, J¼8.3 Hz), 7.29 (2H, dd, J¼7.5, 7.3 Hz), 7.23 (2H, d,
J¼8.3 Hz), 7.23–7.19 (3H, m, overlapped), 6.01 (1H, q,
J¼1.3 Hz), 3.68–3.63 (1H, m), 2.81–2.76 (1H, m), 2.66–
2.60 (1H, m), 2.41 (3H, s), 2.35–2.28 (1H, m), 2.24–2.17
(1H, m), 2.01–1.95 (1H, m), 1.95–1.87 (1H, m), 1.61 (3H,
d, J¼1.3 Hz); 13C NMR (125 MHz, CDCl3) d 143.4,
141.5, 133.4, 129.4, 128.5, 128.4, 127.7, 125.8, 124.6,
123.3, 59.9, 40.3, 37.8, 31.1, 21.6, 13.5; IR (ZnSe) 2924,
1597, 1495, 1454, 1346, 1163, 1090, 1030, 982, 814, 700,
667, 592, 548 cmꢀ1. Found: C, 70.14; H, 6.96; N, 3.90%.
Calcd for C20H23NO2S: C, 70.35; H, 6.79; N, 4.10%.
5.2.6.2. (Z)-3-(Bromomethylene)-5-phenylpentane-1-
thiol (Z-13d). Colorless oil; H NMR (500 MHz, CDCl3)
1
d 7.29 (2H, dd, J¼7.4, 7.4 Hz), 7.21 (1H, t, J¼7.4 Hz),
7.16 (2H, d, J¼7.4 Hz), 6.01 (1H, s), 2.74 (2H, t,
J¼8.0 Hz), 2.66 (2H, dt, J¼7.7, 7.8 Hz), 2.57 (2H, t,
J¼7.8 Hz), 2.43 (2H, t, J¼8.0 Hz), 1.46 (1H, t, J¼7.7 Hz);
13C NMR (125 MHz, CDCl3) d 142.6, 140.8, 128.5, 128.3,
126.2, 104.1, 38.0, 37.3, 34.1, 21.9; IR (ZnSe) 2925, 1626,
1603, 1496, 1454, 1281, 1076, 1030, 748, 698 cmꢀ1
.
5.3.2. 4-Methyl-2-phenyl-1-tosyl-2,3-dihydro-1H-pyrrole
(20b). White powder; mp 105 ꢁC; 1H NMR (500 MHz,
CDCl3) d 7.64 (2H, d, J¼8.1 Hz), 7.33–7.26 (5H, m,
HRMS (FAB+) Found: 271.0130. Calcd for C12H16BrS
(M+H+): 271.0156.

5952
H. Miyauchi et al. / Tetrahedron 63 (2007) 5940–5953
overlapped), 7.29 (2H, d, J¼8.1 Hz), 6.20 (1H, s), 4.72 (1H,
dd, J¼10.7, 5.7 Hz), 2.77 (1H, dd, J¼16.3, 5.7 Hz), 2.43
(3H, s), 2.29 (1H, dd, J¼16.3, 10.7 Hz), 1.65 (3H, s); 13C
NMR (125 MHz, CDCl3) d 143.5, 143.0, 133.8, 129.5,
128.5, 127.7, 127.4, 126.2, 124.7, 121.6, 63.2, 44.6, 21.6,
13.4; IR (ZnSe) 2916, 1597, 1495, 1350, 1163, 1090,
1030, 976, 814, 758, 700, 669, 592 cmꢀ1. Found: C,
68.79; H, 6.30; N, 4.35%. Calcd for C18H19NO2S: C,
68.98; H, 6.11; N, 4.47%.
2.42 (2H, t, J¼8.0 Hz); 13C NMR (125 MHz, CDCl3)
d 141.7, 136.7, 128.4, 128.3, 125.9, 117.9, 38.2, 34.5,
33.4, 32.2; IR (ZnSe) 2924, 1603, 1496, 1454, 1232, 1074,
1030, 806, 748, 698 cmꢀ1
.
HRMS (FAB+) Found:
191.0896. Calcd for C12H15S (M+H+): 191.0895.
5.3.8. 2-Phenethyl-4-(propan-2-ylidene)thietane (24).
Colorless oil; 1H NMR (500 MHz, CDCl3) d 7.22–7.19
(2H, m), 7.13–7.08 (3H, m, overlapped), 3.49–3.39 (2H,
m, overlapped), 2.95–2.92 (1H, m), 2.63–2.57 (1H, m),
2.52–2.46 (1H, m), 2.11–1.97 (2H, m, overlapped), 1.45
(3H, s), 1.39 (3H, s); 13C NMR (125 MHz, CDCl3) d
141.1, 128.4, 128.4, 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%.
5.3.3. 4-Phenethyl-1-tosyl-2,3-dihydro-1H-pyrrole (20d).
Colorless oil; H NMR (500 MHz, CDCl3) d 7.59 (2H, d,
1
J¼8.3 Hz), 7.29 (2H, d, J¼8.3 Hz), 7.26 (2H, dd, J¼7.3,
7.3 Hz), 7.19 (1H, t, J¼7.3 Hz), 7.11 (2H, d, J¼7.3 Hz),
6.09 (1H, s), 3.45 (2H, t, J¼9.0 Hz), 2.69 (2H, t, J¼
7.6 Hz), 2.44 (3H, s), 2.34 (2H, t, J¼9.0 Hz), 2.30 (2H, t,
J¼7.6 Hz); 13C NMR (125 MHz, CDCl3) d 143.5, 141.2,
132.5, 129.6, 128.4, 128.1, 127.7, 126.2, 126.0, 124.8,
47.5, 33.9, 32.4, 29.8, 21.6; IR (ZnSe) 2922, 1597, 1495,
Acknowledgements
1454, 1348, 1161, 1090, 1032, 814, 700, 667, 592 cmꢀ1
.
This work was supported by a Grant-in-Aid for The 21st
Century COE Program for Frontiers in Fundamental Chem-
istry and Grant-in-Aid for Scientific Research on Priority
Areas ‘Advanced Molecular Transformations of Carbon
Resources’ (K.A.) from the Ministry of Education, Culture,
Sports, Science and Technology, Japan. S.C. thanks Astellas
Foundation for Research on Medicinal Resources for the
financial support.
HRMS (FAB+) Found: 328.1378. Calcd for C19H22NO2S
(M+H+): 328.1371.
5.3.4. 3-Methyl-1-(phenylsulfonyl)cyclopent-2-enecarbo-
nitrile (22c). White powder; mp 95 ꢁC; 1H NMR (500 MHz,
CDCl3) d 8.00 (2H, d, J¼7.5 Hz), 7.76 (1H, t, J¼7.6 Hz),
7.64 (2H, dd, J¼7.6, 7.5 Hz), 5.18 (1H, s), 2.94–2.90 (1H,
m), 2.66–2.59 (1H, m), 2.53–2.44 (2H, m, overlapped),
1.89 (3H, s); 13C NMR (125 MHz, CDCl3) d 155.7, 134.9,
134.7, 130.4, 129.3, 117.2, 116.5, 72.9, 36.4, 32.2, 16.8;
IR (ZnSe) 1647, 1583, 1446, 1325, 1149, 1086, 725, 688,
594, 559 cmꢀ1. Found: C, 62.95; H, 5.59; N, 5.49%. Calcd
for C13H13NO2S: C, 63.13; H, 5.30; N, 5.66%.
References and notes
1. Hughes, E. D.; Juliusburger, F.; Masterman, S.; Topley, B.;
Weiss, J. J. Chem. Soc. 1935, 1525.
2. For reviews, see: (a) Rapport, Z. Acc. Chem. Res. 1992, 25, 474;
(b) Okuyama, T.; Lodder, G. Advances in Physical Organic
Chemistry; Tidwell, T. T., Richard, J. P., Eds.; Academic:
New York, NY, 2002; Vol. 37, pp 1–56; (c) Okuyama, T.
J. Synth. Org. Chem. Jpn. 2006, 64, 348.
3. (a) Miller, S. I.; Yonan, P. K. J. Am. Chem. Soc. 1957, 79, 5931;
(b) Miller, S. I. Advances in Physical Organic Chemistry; Gold,
V., Ed.; Academic: New York, NY, 1968; Vol. 6, pp 185–332.
4. Kelsey, D. R.; Bergman, R. G. J. Am. Chem. Soc. 1971, 93,
1953.
5.3.5. 3-Phenethyl-1-(phenylsulfonyl)cyclopent-2-ene-
carbonitrile (22d). Colorless oil; 1H NMR (500 MHz,
CDCl3) d 7.86 (2H, d, J¼8.0 Hz), 7.73 (1H, t, J¼7.5 Hz),
7.58 (2H, dd, J¼8.0, 7.5 Hz), 7.33 (2H, dd, J¼7.4,
7.4 Hz), 7.24 (1H, t, J¼7.4 Hz), 7.19 (2H, d, J¼7.4 Hz),
5.13 (1H, s), 2.97–2.91 (1H, m), 2.82 (2H, t, J¼7.7 Hz),
2.75–2.65 (1H, m), 2.57–2.47 (4H, m, overlapped); 13C
NMR (125 MHz, CDCl3) d 158.9, 140.5, 134.9, 134.6,
130.3, 129.2, 128.5, 128.2, 126.2, 117.1, 116.2, 72.6, 35.0,
33.3, 32.6, 31.7; IR (ZnSe) 2924, 1641, 1603, 1583, 1446,
1325, 1149, 1084, 725, 688, 594 cmꢀ1. HRMS (FAB+)
Found: 338.1193. Calcd for C20H20NO2S (M+H+):
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