Synthesis of thiochromans based on indirect cation pool method

Article abstract of DOI:10.3987/COM-08-S(N)64

A method for the synthesis of thiochromans based on the reactions of stilbenes and alkoxycarbenium ion pools, which were generated and accumulated by the reaction of anodically generated ArS(ArSSAr)⁺ with thioacetals, has been developed.

Full text of DOI:10.3987/COM-08-S(N)64

HETEROCYCLES, Vol. 76, No. 2, 2008
1103
HETEROCYCLES, Vol. 76, No. 2, 2008, pp. 1103 - 1119. © The Japan Institute of Heterocyclic Chemistry
Received, 27th March, 2008, Accepted, 13th May, 2008, Published online, 15th May, 2008. COM-08-S(N)64
SYNTHESIS OF THIOCHROMANS BASED ON INDIRECT CATION
POOL METHOD
Kouichi Matsumoto, Koji Ueoka, Shunsuke Fujie, Seiji Suga,* and Jun-ichi
Yoshida*
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of
Engineering, Kyoto University, Nishikyo-ku, Kyoto 615-8510, Japan. E-mail:
yoshida@sbchem.kyoto-u.ac.jp
This paper is dedicated to Professor Ryoji Noyori on the occasion of his 70th
birthday
Abstract – A method for the synthesis of thiochromans based on the reactions of
stilbenes and alkoxycarbenium ion pools, which were generated and accumulated
by the reaction of anodically generated ArS(ArSSAr)+ with thioacetals, has been
developed.
INTRODUCTION
The chemistry of thiochromans (3,4-dihydro-2H-1-benzothiopyrans) attracts much attention, because of
their utility as synthetic intermediates as well as strong biological activity.1 To date, many methods for
the synthesis of thiochromans have been reported.2 The cationic polar cycloaddition of phenylthionium
ion with olefins developed by Ishibashi is one of the most straightforward approaches to construction of
thiochroman systems.3a-d Katritzky reported an efficient synthesis of novel thiochromans using a similar
strategy.3e Ishino developed an unique acid-catalyzed intermolecular cycloaddition of α,β-unsaturated
aldehydes and thiophenols.4 An efficient one-pot synthesis of thiochromans via intramolecular
[4+2]cycloaddition of o-thiobenzoquinone methides was recently reported by Saito.5 All these examples,
however, involve a coupling process of two different components. To our knowledge, there is no method
involving assembly of three different components, which should allow us to synthesize a variety of
thiochroman derivatives.
We have developed the “cation pool” method,6 in which highly reactive organic cations are generated and
accumulated by the low temperature electrochemical oxidation of substrates. We have also developed the
indirect cation pool method7 consisting of the following three steps (Scheme 1). The highly reactive

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HETEROCYCLES, Vol. 76, No. 2, 2008
ArS(ArSSAr)+ 8 is generated and accumulated by the low temperature electrochemical oxidation of
o
ArSSAr9 at -78 C (step 1), and is subsequently allowed to react with a thioacetal10 (1) to generate an
“alkoxycarbenium ion pool11 (2) ” (step 2). The cation pool of 2 thus generated is allowed to react with a
carbon nucleophile such as allyltrimethylsilane to give the corresponding C-C bond formation product
(step 3a). During the course of our study using various olefins as carbon nucleophiles,12 we found that
compounds having the thiochroman skeleton (3) were formed in the reaction with stilbene derivatives
(step 3b). The reaction involves an assembly of three components, i.e., 2, a stilbene derivative, and
ArSSAr. Herein, we wish to report the details of this method for the synthesis of thiochromans based on
the indirect cation pool method.
Scheme 1. Indirect generation of the alkoxycarbenium ion pools and their reactions with carbon
nucleophiles
step 1
ArSSAr
ArS(ArSSAr)
step 3a
SiMe3
e
step 2
R
OMe
anode
R
OMe
OMe
SAr
R
2
1
S
R
Ar'
Ar'
step 3b
Ar'
+
ArSSAr
X
Ar'
3
RESULTS AND DISCUSSION
We examined various reaction conditions for the reaction of alkoxycarbenium ion 2a with cis-stilbene,
the best result was obtained under the following conditions (Table 1, entry 1). A solution of
− 12
ArS(ArSSAr)+ B(C6F5)4
was generated and accumulated by the anodic oxidation of ArSSAr (1.00
o
mmol) in Bu4NB(C6F5)4/CH2Cl2 at -78 C (0.30 F/mol).13 To the anodic solution was added thiocetal 1a
(0.30 mmol) at -78 oC, and the solution was stirred for 5 min. Then, cis-stilbene (0.20 mmol) was added,
o
and the temperature was rapidly increased to 0 C. After stirring for 10 min at the same temperature,
triethylamine was added to the solution. Thiochroman 3a was obtained in 65% yield (d.r. 2.6:1). When
trans-stilbene was used as a carbon nucleophile, 3a was also obtained (entry 2). Because a similar
diastereoselectivity was observed in both cases, the reactions seem to proceed by a stepwise mechanism
involving cationic intermediates rather than a concerted mechanism (vide infra). The reactions of other
stilbene derivatives having electron-donating substituents or electron-withdrawing substituents at 4,4’ or

HETEROCYCLES, Vol. 76, No. 2, 2008
1105
2,2’-positions also gave thiochromans (entries 3-6). Although four diastereomers could be formed in all
cases, two diastereomers were mainly obtained except for 3e. The reactions of other alkenes such as
1,1-diphenylethene and 1,1’,2,2’-tetramethylethene gave complex mixtures.
Table 1. Reactions of the alkoxycarbenium ion pool 2a with stilbene derivatives.a
R2
R1
-e, -78 oC
OMe
ArSSAr
(Ar = p-FC6H4)
ArS(ArSSAr)
5 min, -78 oC
SAr
S
OMe
stilbene
10 min, 0 oC
F
C8H17
C8H17
(Ar = p-FC6H4)
H17C8
2a
R2
R1
3
1a
R1
3
R2
% yieldb
entry
stilbene
diastereomer ratio
1
2
cis-stilbene
H
H
H
H
3a
3a
2.6:1
2.8:1
65
70
trans-stilbene
trans-4,4'-dimethylstilbene
trans-4,4'-dimethoxystilbene
trans-4,4'-dichlorostilbene
77
3
4
5
Me
OMe
Cl
H
H
H
3b
3c
3d
3.3:1
1.4:1
1.9:1
21d
43e
trans-2,2'-dimethoxystilbene
53c
6
H
OMe
was
3e
exclusive
a
ArSSAr
(Ar
=
p-FC6H4)
(1.00
mmol)
electrolyzed
in
0.1
M
Bu4NB(C6F5)4/CH2Cl2
-
(8 mL) at -78 oC using 0.30 F/mol of electricity. The solution of thus obtained ArS(ArSSAr)+B(C6F5)4 was allowed to
react with thioacetal 1a (0.30
was added and the resulting solution was stirred at
mmol) at -78 oC for
5
min. Then stilbene (0.20 mmol)
0
oC for 10 min. The reaction was
quenched with Et3N (-78 oC). b Isolated yield. c 1H NMR yield using Cl2CHCHCl2 as an internal standard. d The purity of
the product was ca. 85%. e The purity of the product was ca. 95%.
In order to test the applicability of the present method, the reactions of several alkoxycarbenium ions,
which were generated from other thioacetals, with cis-stilbene were examined (Table 2). When the
thioacetal having an ethoxy group instead of a methoxy group was used, thiochroman 3a was also
obtained in 35% yield (entry 1). The diastereoselectivity was similar to that observed in the reaction of 1a
(Table 1, entry 1). Although the reactions of the thioacetals bearing a phenyl and a 4-chlorophenyl groups
gave the corresponding products (entries 2 and 3), the thioacetal having a 4-methoxyphenyl group was
not effective in this reaction. Alkyl-substituted thioacetals could also be utilized for the construction of
thiochromans (entries 4 and 5). NMR measurements (proton homonuclear NOE and coupling constants)
of 3f, which was carried out according to the Katritzky’s procedure,3e showed that three phenyl groups of
the major isomer of 3f were in all trans configuration.

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HETEROCYCLES, Vol. 76, No. 2, 2008
Table 2. Reactions of other alkoxycarbenium ion pools with
cis-stilbene.a
-e, -78 oC
ArSSAr
(Ar = p-FC6H4)
ArS(ArSSAr)
5 min, -78 o
S
Ph
Ph
OR'
thioacetal
(Ar = p-FC6H4)
F
10 min, 0 oC
C
R
R
3
% yieldb
35
entry
1
thioacetal
OEt
R
3
diastereomer ratio
3a
2.6:1
C8H17
C8H17
SAr
OMe
2
3
Ph
3f
>15:1
2.2:1
53
67
SAr
OMe
SAr
3g
p-ClC6H4
Cl
OMe
SAr
3h
3i
2.4:1
3.8:1
37
61
C6H11
4
5
OMe
SAr
PhCH2CH2
a
ArSSAr (Ar = p-FC6H4) (1.00 mmol) was electrolyzed in 0.1 M Bu4NB(C6F5)4/CH2Cl2 (8 mL) at -78 oC using 0.30
-
F/mol of electricity. The solution of thus obtained ArS(ArSSAr)+B(C6F5)4 was allowed to react with a thioacetal (0.30
mmol) at -78 oC for 5 min. Then cis-stilbene (0.20 mmol) was added and the resulting solution was stirred at 0 oC for
10 min. The reaction was quenched with Et3N (-78 oC). b Isolated yield.
Next, the reactions using other ArS(ArSSAr)+, which were generated from the corresponding ArSSAr
having a different para-substituent on the aromatic ring, were examined. The results obtained with 2a and
cis-stilbene are shown in Table 3. Although ArS(ArSSAr)+ bearing a chloro group on the aryl groups
gave 3k in good yield (entry 2), those without a substituent and bearing a methyl group led to the
formation of the desired products in moderate yields (entries 1 and 3).
The present reaction seems to proceed by a stepwise mechanism involving cationic intermediates as
shown in Scheme 2. In the first step, 2 reacts with a stilbene derivative to form cationic intermediate I.
The formation of 3a with similar diastereoselectivities both from cis- and trans-stilbene suggests the
intermediacy of I. The reaction of ArSSAr with I gives intermediate II, and the formal elimination of the

HETEROCYCLES, Vol. 76, No. 2, 2008
1107
methoxyl group from II gives rise to the formation of cationic intermediate III, which undergoes
Friedel-Crafts reaction to give 3.
Table 3. Synthesis of thiochromans using other ArS(ArSSAr)+.a
-e, -78 o
OMe
SAr
C
ArSSAr
ArS(ArSSAr)
5 min, -78 o
S
Ph
Ph
OMe
10 min, 0 oC
R
C
C8H17
C8H17
2a
C8H17
1a
3
% yieldb
28
entry
1
SAr
R
H
3
diastereomer ratio
2.6:1
3j
S
S
2
3
Cl
3k
3l
3.1:1
2.4:1
74
Cl
Me
32c
S
Me
a
ArSSAr (1.00 mmol) was electrolyzed in 0.1 M Bu4NB(C6F5)4/CH2Cl2 (8 mL) at -78 oC using 0.30 F/mol of electricity.
-
The solution of thus obtained ArS(ArSSAr)+B(C6F5)4 was allowed to react with 1a (0.30 mmol) at -78 oC for 5 min.
Then cis-stilbene (0.20 mmol) was added and the resulting solution was stirred at 0 oC for 10 min. The reaction was
quenched with Et3N (-78 oC). b Isolated yield. c The purity of the product was ca. 85%.
Scheme 2. Plausible mechanism
ArS(ArSSAr)
OMe
SAr
OMe
R
R
2
1
ArSSAr
ArSSAr
Ar'
Ar'
Ar'
Ar'
MeO
R
I
X
S
X
S
H
H
S
R
Ar'
Ar'
Ar'
Ar'
Ar'
Ar'
X
MeO
R
R
3
III
II

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HETEROCYCLES, Vol. 76, No. 2, 2008
CONCLUSION
The reactions of alkoxycarbenium ion pools generated by the indirect cation pool method with a variety
of stilbene derivatives led to the formation of the corresponding thiochromans. This reaction provides a
versatile method for the construction of the thiochroman derivatives by assembling three different
components, i.e., an alkoxycarbenium ion, a stilbene derivative, and ArSSAr. It is hoped that a variety of
molecules having a thiochroman skeleton will be synthesized based on the present method.
EXPERIMENTAL
1
13
General Remarks. H and C NMR spectra were recorded in CDCl3 on a Varian Gemini 2000 (1H 300
MHz, 13C 75 MHz), Varian MERCURY plus-400 (1H 400 MHz, 13C 100 MHz), or JEOL ECA-600P (1H
600 MHz, 13C 150 MHz) spectrometer with Me4Si as an internal standard unless otherwise noted. EI mass
spectra were recorded on JMS-SX102A spectrometer. FAB mass spectra were recorded on
JMX-HX110A spectrometer. IR spectra were measured with a SHIMADZU FTIR 1600 spectrometer.
Thin-layer chromatography (TLC) was carried out by using Merck precoated silica gel F254 plates
(thickness 0.25 mm). Flash chromatography was carried out on a column of silica gel (Kanto Chem. Co.,
Silica Gel N, spherical, neutral, 40-100 µm). Gel permeation chromatography (GPC) was carried out on
Japan Analytical Industry LC-908 equipped with JAIGEL-1H and 2H using CHCl3 as eluent. All
reactions were carried out under Ar atmosphere unless otherwise noted.
Materials. Bu4NB(C6F5)4 was prepared from Bu4NBr (35.1 g, 109 mmol) and aqueous solution of
NaB(C6F5)4 (10 wt%, 499 g, 71.1 mmol) in water (100 mL). The mixture was diluted with EtOAc and
was washed with water. After drying over MgSO4 and removal of solvent, the precipitate was
o
recrystallized from CHCl3/hexane and dried at 50 C/1 mmHg overnight to give Bu4NB(C6F5)4 (65.1 g,
70.6 mmol, 99%). Dichloromethane was washed with water, distilled from P2O5, redistilled from dried
K2CO3 to remove a trace amount of acid, and stored over molecular sieves 4A. Dry THF was used as
obtained (Kanto Chemical Co., Inc.). ArSSAr (Ar = p-FC6H4) was prepared according to the procedure in
the literature,14 and identified by the comparison of its spectral data with that of authentic sample.15
trans-2,2’-Methoxystilbene was prepared according to the procedure in the literature,16 and identified by
the comparison of its spectral data with that of authentic sample.17
Thioacetals.
1-Methoxy-1-phenylthiononane,
1-methoxy-1-(4-methylphenylthio)nonane
and
1-methoxy-1-(4-chlorophenylthio)nonane were prepared according to the literature procedures.8
1-Methoxy-1-(4-fluorophenylthio)nonane (1a). To a solution of pelargonaldehyde dimethyl acetal (4.03
g, 21.4 mmol) and p-fluorothiophenol (2.30 mL, 21.5 mmol) in toluene (180 mL), was added BF3-OEt2
o
(2.7 mL, 21.5 mmol) at -78 C. The solution was stirred for 2 h. Saturated aqueous NaHCO3 was added.
The reaction mixture was partitioned between Et2O and saturated aqueous NaHCO3. The organic phase

HETEROCYCLES, Vol. 76, No. 2, 2008
1109
was separated and washed with saturated aqueous NaHCO3 and dried over MgSO4. After removal of the
solvent, the crude product was purified by flash chromatography (hexane/EtOAc 30:1) to give the title
1
compound (1a) (4.23 g, 14.9 mmol, 70%): TLC Rf 0.28 (hexane/EtOAc 20:1); H NMR (400 MHz,
CDCl3) δ 0.87 (t, J = 6.8 Hz, 3H), 1.18-1.32 (m, 10H), 1.34-1.46 (m, 2H), 1.58-1.74 (m, 2H), 3.47 (s, 3H),
4.51 (t, J = 6.4 Hz, 1H), 6.94-7.02 (m, 2H), 7.39-7.45 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 14.1, 22.6,
26.2, 29.1, 29.2, 29.4, 31.8, 35.5, 55.5, 91.0, 115.8 (d, J = 21.7 Hz), 127.9 (d, J = 3.4 Hz), 136.1 (d, J =
8.0 Hz), 162.7 (d, J = 246.0 Hz); IR (neat) 2926, 1590, 1491, 830 cm-1; LRMS (EI) m/z 284 (M+), 157
(M+-SC6H4F); HRMS (EI) calcd for C16H25FOS (M+) 284.1610, found 284.1605.
1-Ethoxy-1-(4-fluorophenylthio)nonane. To a solution of pelargonaldehyde (16 mL, 93 mmol) in EtOH
(70 mL) was added BF3-OEt2 (12.5 mL, 99.5 mmol). Then the mixture was stirred at reflux condition
overnight. Saturated aqueous NaHCO3 was added. The reaction mixture was partitioned between Et2O
and saturated aqueous NaHCO3. The organic phase was separated and washed with saturated aqueous
NaHCO3 and dried over MgSO4. After removal of the solvent, the crude product was purified by
o
distillation (80 C, 1.79 mmHg) and flash chromatography (hexane/EtOAc 100:1) to give pelargonalde-
hyde diethyl acetal (1.91 g, 8.83 mmol, 9%). To a solution of pelargonaldehyde diethyl acetal (1.02 g,
4.70 mmol) and p-fluorothiophenol (0.55 mL, 5.16 mmol) in toluene (50 mL), was added BF3-OEt2 (0.75
mL, 5.97 mmol) at -78 oC. The solution was stirred for 2 h. Et3N (2 mL) was added. The reaction mixture
was partitioned between Et2O and saturated aqueous NaHCO3. The organic phase was separated and
washed with saturated aqueous NaHCO3 and dried over MgSO4. After removal of the solvent, the crude
product was purified by flash chromatography (hexane/EtOAc 50:1) to give the title compound (722 mg,
2.42 mmol, 51%): TLC Rf 0.52 (hexane/EtOAc 20:1); 1H NMR (400 MHz, CDCl3) δ 0.87 (t, J = 6.8 Hz,
3H), 1.18-1.46 (m, 15H), 1.60-1.74 (m, 2H), 3.47 (dq, J = 9.4, 7.2 Hz, 1H), 3.95 (dq, J = 9.4, 7.2 Hz, 1H),
4.58 (t, J = 6.4 Hz, 1H), 6.94-7.02 (m, 2H), 7.40-7.45 (m, 2H); 13C NMR (150 MHz, CDCl3) δ 14.1, 14.8,
22.6, 26.2, 29.1, 29.2, 29.4, 31.8, 35.8, 63.5, 89.3, 115.7 (d, J = 21.5 Hz), 127.9, 136.2 (d, J = 8.6 Hz),
162.6 (d, J = 245.6 Hz); IR (neat) 2926, 1489, 1086 cm-1; LRMS (EI) m/z 298 (M+), 253 (M+-OEt), 171
(M+-SC6H4F), 127 (M+-EtOCHC8H17); HRMS (EI) calcd for C17H27FOS (M+) 298.1767, found 298.1765.
Methyl phenyl(4-fluorophenylthio)methyl ether. To a solution of benzaldehyde dimethyl acetal (1.94 g,
12.7 mmol) and p-fluorothiophenol (1.35 mL, 12.7 mmol) in toluene (100 mL), was added BF3-OEt2
(1.60 mL, 12.6 mmol) at -78 oC. The solution was stirred for 2 h. Saturated aqueous NaHCO3 was added.
The reaction mixture was partitioned between Et2O and saturated aqueous NaHCO3. The organic phase
was separated and washed with saturated aqueous NaHCO3 and dried over MgSO4. After removal of the
solvent, the crude product was purified by flash chromatography (hexane/EtOAc 100:1) to give the title
1
compound (1.92 g, 7.73 mmol, 61%): TLC Rf 0.29 (hexane/EtOAc 20:1); H NMR (400 MHz, CDCl3)

1110
HETEROCYCLES, Vol. 76, No. 2, 2008
13
δ 3.55 (s, 3H), 5.63 (s, 1H), 6.85-6.91 (m, 2H), 7.15-7.25 (m, 7H); C NMR (100 MHz, CDCl3) δ 56.6,
91.1, 115.4 (d, J = 21.4 Hz), 126.0, 127.0, 127.7, 127.8, 136.6 (d, J = 8.3 Hz), 138.9, 162.7 (d, J = 245.6
Hz); IR (neat) 1590, 1489, 1223 cm-1; LRMS (EI) m/z 248 (M+), 217 (M+-OMe), 121 (M+-SC6H4F), 77
(M+-MeOCHSC6H4F); HRMS (EI) calcd for C14H13FOS (M+) 248.0671, found 248.0677.
Methyl 4-chlorophenyl(4-fluorophenylthio)methyl ether. To a solution of p-chlorobenzaldehyde (8.19
g, 58.3 mmol) in MeOH (55 mL) was added BF3-OEt2 (9.0 mL, 71.0 mmol). Then the mixture was stirred
at reflux condition overnight. Saturated aqueous NaHCO3 was added. The reaction mixture was
partitioned between Et2O and saturated aqueous NaHCO3. The organic phase was separated and washed
with saturated aqueous NaHCO3 and dried over MgSO4. The removal of the solvent gave
p-chlorobenzaldehyde dimethyl acetal (8.34 g), and this material was used for the subsequent reaction
without further purification. To a solution of p-chlorobenzaldehyde dimethyl acetal (4.68 g, ca. 25 mmol)
and p-fluorothiophenol (2.60 mL, 24.4 mmol) in toluene (150 mL), was added BF3-OEt2 (3.50 mL, 27.6
o
mmol) at -78 C. The solution was stirred for 2 h. Et3N (8 mL) was added. The reaction mixture was
partitioned between Et2O and saturated aqueous NaHCO3. The organic phase was separated and washed
with saturated aqueous NaHCO3 and dried over MgSO4. After removal of the solvent, the crude product
was purified by flash chromatography (hexane/EtOAc 20:1) to give the title compound (3.58 g, 12.7
mmol, ca. 51%): TLC Rf 0.29 (hexane/EtOAc 20:1); 1H NMR (400 MHz, CDCl3) δ 3.57 (s, 3H), 5.59 (s,
1H), 6.85-6.92 (m, 2H), 7.06-7.11 (m, 2H), 7.15-7.20 (m, 4H); 13C NMR (150 MHz, CDCl3) δ 56.5, 90.3,
115.6 (d, J = 21.5 Hz), 126.3, 127.4, 128.0, 133.4, 137.0 (d, J = 7.2 Hz), 137.8, 163.0 (d, J = 247.0 Hz);
IR (KBr) 1588, 1489, 1219 cm-1; LRMS (FAB) m/z 281 (M+-H), 251 (M+-OMe), 171 (M+-C6H4Cl), 155
(M+-SC6H4F); HRMS (FAB) calcd for C14H12ClFOS (M+) 282.0281, found 282.0278.
Methyl cyclohexyl(4-fluorophenylthio)methyl ether. To a solution of cyclohexanecarbaldehyde (7.38 g,
66 mmol) in MeOH (40 mL) was added BF3-OEt2 (10.0 mL, 78.9 mmol). Then the mixture was stirred at
reflux condition overnight. Saturated aqueous NaHCO3 was added. The reaction mixture was partitioned
between Et2O and saturated aqueous NaHCO3. The organic phase was separated and washed with
saturated aqueous NaHCO3 and dried over MgSO4. The removal of the solvent gave
cyclohexanecarbaldehyde dimethyl acetal (8.06 g), and this material was used for the subsequent reaction
without further purification. To a solution of cyclohexanecarbaldehyde dimethyl acetal (2.14 g, ca. 14
mmol) and p-fluorothiophenol (1.5 mL, 14.0 mmol) in CH2Cl2 (90 mL), was added BF3-OEt2 (1.70 mL,
o
13.4 mmol) at -78 C. The solution was stirred for 2 h. Saturated aqueous NaHCO3 was added. The
reaction mixture was partitioned between Et2O and saturated aqueous NaHCO3. The organic phase was
separated and washed with saturated aqueous NaHCO3 and dried over MgSO4. After removal of the
solvent, the crude product was purified by flash chromatography (hexane/EtOAc 50:1) to give the title

HETEROCYCLES, Vol. 76, No. 2, 2008
1111
1
compound (1.80 g, 7.1 mmol, ca. 51%): TLC Rf 0.39 (hexane/EtOAc 20:1); H NMR (400 MHz, CDCl3)
δ 1.00-1.24 (m, 5H), 1.55-1.66 (m, 2H), 1.68-1.80 (m, 2H), 1.88-2.02 (m, 2H), 3.42 (s, 3H), 4.28 (d, J =
7.2 Hz, 1H), 6.94-7.02 (m, 2H), 7.41-7.48 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 26.0, 26.1, 26.5, 29.5,
30.0, 42.9, 56.5, 97.9, 115.8 (d, J = 21.8 Hz), 129.43 (d, J = 3.2 Hz), 135.5 (d, J = 7.9 Hz), 162.2 (d, J =
244.7 Hz); IR (neat) 2926, 1590, 1489 cm-1; LRMS (EI) m/z 254 (M+), 223 (M+-OMe), 171 (M+-C6H11),
127 (M+-SC6H4F), 83 (M+-MeOCHSC6H4F); HRMS (EI) calcd for C14H19FOS (M+) 254.1141, found
254.1130.
Methyl 2-phenylethyl(4-fluorophenylthio)methyl ether. To a solution of 3-phenylpropionaldehyde
(7.88 g, 59 mmol) in MeOH (100 mL) was added BF3-OEt2 (10.0 mL, 78.9 mmol). Then, the mixture was
stirred at reflux condition overnight. Saturated aqueous NaHCO3 was added. The reaction mixture was
partitioned between Et2O and saturated aqueous NaHCO3. The organic phase was separated and washed
with saturated aqueous NaHCO3 and dried over MgSO4. The removal of the solvent gave
3-phenylpropionaldehyde dimethyl acetal (9.34 g), and this material was used for the subsequent reaction
without further purification. To a solution of 3-phenylpropionaldehyde dimethyl acetal (1.53 g, ca. 8.5
mmol) and p-fluorothiophenol (1.0 mL, 9.4 mmol) in toluene (80 mL), was added BF3-OEt2 (1.1 mL, 8.7
o
mmol) at -78 C. The solution was stirred for 2 h. Saturated aqueous NaHCO3 was added. The reaction
mixture was partitioned between Et2O and saturated aqueous NaHCO3. The organic phase was separated
and washed with saturated aqueous NaHCO3 and dried over MgSO4. After removal of the solvent, the
crude product was purified by flash chromatography (hexane/EtOAc 20:1) to give the title compound
1
(1.96 g, 7.10 mmol, ca. 84%): TLC Rf 0.35 (hexane/EtOAc 20:1); H NMR (400 MHz, CDCl3)
δ 1.90-2.06 (m, 2H), 2.66-2.80 (m, 2H), 3.48 (s, 3H), 4.44 (t, J = 6.6 Hz, 1H), 6.95-7.01 (m, 2H),
7.10-7.20 (m, 3H), 7.23-7.28 (m, 2H), 7.39-7.45 (m, 2H); 13C NMR (150 MHz, CDCl3) δ 32.3, 37.1, 55.6,
89.6, 115.8 (d, J = 21.5 Hz), 126.0, 127.3, 128.4, 128.5, 136.3 (d, J = 7.2 Hz), 141.0, 162.7 (d, J = 247.0
Hz); IR (neat) 1590, 1489, 1455 cm-1; LRMS (EI) m/z 276 (M+), 149 (M+-SC6H4F); HRMS (EI) calcd for
C16H17FOS (M+) 276.0984, found 276.0981.
Reactions of Indirect Generated Alkoxycarbenium Ion with Stilbenes.
6-Fluoro-4-octyl-2,3-diphenylthiochroman (3a): (Typical Procedure). The anodic oxidation was
carried out in an H-type divided cell (4G glass filter) equipped with a carbon felt anode and a platinum
plate cathode (40 mm x 20 mm). In the anodic chamber was placed a solution of ArSSAr (Ar = p-FC6H4)
(254.4 mg, 1.00 mmol) in 0.1 M Bu4NB(C6F5)4/CH2Cl2 (8.0 mL). In the cathodic chamber were placed
0.1 M Bu4NB(C6F5)4/CH2Cl2 (8.0 mL) and trifluoromethanesulfonic acid (52.6 mg, 0.351 mmol). The
o
constant current electrolysis (8 mA) was carried out at -78 C with magnetic stirring until 0.30 F/mol of
-
electricity was consumed. To the anodic chamber containing electrogenerated ArS(ArSSAr)+B(C6F5)4 ,

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HETEROCYCLES, Vol. 76, No. 2, 2008
was added 1-methoxy-1-(4-fluorophenylthio)nonane (1a) (85.2 mg, 0.300 mmol) and the mixture was
o
stirred for 5 min at -78 C. Then, to thus generated alkoxycarbenium ion pool was added cis-stilbene
o
(36.6 mg, 0.203 mmol) and the reaction mixture was stirred for 10 min at 0 C. The reaction was
o
quenched with Et3N (1 mL) at -78 C. The solvent was removed under reduced pressure and the residue
was quickly filtered through a short column (2 x 3 cm) of silica gel to remove Bu4NB(C6F5)4. The silica
gel was washed with Et2O (150 mL). The crude product was purified by flash chromatography (hexane/
EtOAc 100:1) (56.7 mg, 65%). This compound was characterized as a mixture of two diastereomers
(2.6:1 by 1H NMR analysis): TLC Rf 0.45 (hexane/EtOAc 20:1); 1H NMR (600 MHz, CDCl3) δ 0.81-0.90
(m, 3H), 1.00-1.48 (m, 14H), 3.11 (t, J = 10.3 Hz, 1H, minor diastereomer), 3.37 (t, J = 3.1 Hz, 1H, major
diastereomer), 3.41-3.48 (m, 1H, major diastereomer), 3.53-3.59 (m, 1H, minor diastereomer), 4.21 (d, J
= 10.3 Hz, 1H, minor diastereomer), 4.38 (d, J = 3.1 Hz, 1H, major diastereomer), 6.42 (dd, J = 10.3, 2.0
Hz, 1H, minor diastereomer), 6.68 (dd, J = 9.6, 2.8 Hz, 1H, major diastereomer), 6.78-7.30 (m, 12H); 13C
NMR (150 MHz, CDCl3) major diastereomer: δ 14.0, 22.6, 27.1, 29.1, 29.2, 29.3, 31.7, 32.3, 40.5, 50.6,
51.4, 114.6 (d, J = 22.5 Hz), 118.5 (d, J = 20.9 Hz), 126.6, 127.0, 127.4 (d, J = 8.0 Hz), 128.1, 128.2,
128.5, 128.6, 129.2, 135.7 (d, J = 6.4 Hz), 140.5, 146.0, 160.2 (d, J = 241.0 Hz), and minor diastereomer
(selected): δ 14.1, 26.3, 31.6, 31.8, 33.8, 46.9, 54.7, 56.0, 113.8 (d, J = 20.9 Hz), 117.3 (d, J = 22.5 Hz),
128.3, 129.3, 130.0, 140.8, 142.6, 143.4; IR (neat) 2926, 1601, 1478 cm-1; LRMS (EI) m/z 432 (M+);
HRMS (EI) calcd for C29H33FS (M+) 432.2287, found 432.2286.
6-Fluoro-4-octyl-2,3-di-p-tolylthiochroman (3b). Prepared from ArSSAr (Ar = p-FC6H4) (257.9 mg,
1.01 mmol), 1-methoxy-1-(4-fluorophenylthio)nonane (1a) (87.0 mg, 0.306 mmol) and
trans-4,4’-dimethylstilbene (38.1 mg, 0.183 mmol) and purified by flash chromatography (hexane/EtOAc
20:1) and purified by GPC (65.1 mg, 77%). This compound was characterized as a mixture of two
1
1
diastereomers (3.3:1 by H NMR analysis): TLC Rf 0.44 (hexane/EtOAc 20:1); H NMR (600 MHz,
CDCl3) δ 0.82-0.90 (m, 3H), 1.05-1.48 (m, 14H), 2.23 (s, 3H, minor diastereomer), 2.25 (s, 3H, minor
diastereomer), 2.29 (s, 3H, major diastereomer), 2.31 (s, 3H, major diastereomer), 3.06 (t, J = 10.7 Hz,
1H, minor diastereomer), 3.31 (t, J = 3.1 Hz, 1H, major diastereomer), 3.40-3.52 (m, 1H), 4.16 (d, J =
10.7 Hz, 1H, minor diastereomer), 4.32 (d, J = 3.1 Hz, 1H, major diastereomer), 6.40-7.22 (m, 11H); 13C
NMR (150 MHz, CDCl3) major diastereomer: δ 14.1, 20.98, 21.01, 22.6, 27.2, 29.1, 29.28, 29.32, 31.8,
32.5, 40.5, 50.2, 51.2, 114.5 (d, J = 23.0 Hz), 118.5 (d, J = 21.5 Hz), 127.4 (d, J = 7.2 Hz), 128.0, 128.5,
128.8, 129.1, 129.2, 135.9 (d, J = 5.7 Hz), 136.1, 136.5, 137.6, 143.2, 160.2 (d, J = 242.7 Hz), and minor
diastereomer (selected): δ 26.4, 31.8, 33.9, 47.2, 54.2, 55.7, 113.7 (d, J = 21.6 Hz), 117.2 (d, J = 23.0 Hz),
139.7, 140.4, 160.3 (d, J = 251.3 Hz); IR (neat) 1514, 1478, 1266 cm-1; LRMS (EI) m/z 460 (M+); HRMS
(EI) calcd for C31H37FS (M+) 460.2600, found 460.2589.

HETEROCYCLES, Vol. 76, No. 2, 2008
1113
6-Fluoro-2,3-bis-(4-methoxyphenyl)-4-octylthiochroman (3c). Prepared from ArSSAr (Ar = p-FC6H4)
(255.3 mg, 1.00 mmol), 1-methoxy-1-(4-fluorophenylthio)nonane (1a) (87.4 mg, 0.307 mmol) and
trans-4,4’-dimethoxystilbene (47.4 mg, 0.197 mmol) and purified by flash chromatography
(hexane/EtOAc 20:1) and purified by GPC (20.4 mg, 21%, purity ca. 85%). This compound was
1
characterized as a mixture of two diastereomers (1.4:1 by H NMR analysis): TLC Rf 0.25
(hexane/EtOAc 20:1); 1H NMR (400 MHz, CDCl3) δ 0.80-0.90 (m, 3H), 1.00-1.50 (m, 14H), 3.01 (t, J =
10.0 Hz, 1H, major diastereomer), 3.27 (t, J = 3.6 Hz, 1H, minor diastereomer), 3.38-3.44 (m, 1H, minor
diastereomer), 3.44-3.52 (m, 1H, major diastereomer), 3.72 (s, 3H, major diastereomer), 3.73 (s, 3H,
major diastereomer), 3.75 (s, 3H, minor diastereomer), 3.77 (s, 3H, minor diastereomer), 4.11 (d, J = 10.0
Hz, 1H, major diastereomer), 4.28 (d, J = 3.6 Hz, 1H, minor diastereomer), 6.38-7.20 (m, 11H); 13C NMR
(100 MHz, CDCl3) major diastereomer: δ 14.3, 22.8, 26.5, 29.26, 29.34, 29.44, 31.9, 34.0, 47.1, 54.0,
55.1, 55.1, 55.3, 113.3, 113.5, 113.6, 113.7, 117.1 (d, J = 22.2 Hz), 128.1 (d, J = 7.9 Hz), 128.9, 130.1,
134.6, 135.5, 141.2 (d, J = 6.7 Hz), 157.6, 157.7, 160.0 (d, J = 240.8 Hz), and minor diastereomer
(selected): δ 27.3, 31.9, 32.6, 40.7, 49.9, 51.0, 55.2, 129.4, 132.5, 138.2, 157.9, 158.2; IR (neat) 2926,
1611, 1512 cm-1; LRMS (EI) m/z 492 (M+); HRMS (EI) calcd for C31H37FO2S (M+) 492.2498, found
492.2500.
2,3-Bis-(4-chlorophenyl)-6-fluoro-4-octylthiochroman (3d). Prepared from ArSSAr (Ar = p-FC6H4)
(267.1 mg, 1.05 mmol), 1-methoxy-1-(4-fluorophenylthio)nonane (1a) (86.4 mg, 0.304 mmol) and
trans-4,4’-dichlorostilbene (48.1 mg, 0.193 mmol) and purified by flash chromatography (hexane/EtOAc
10:1) and purified by GPC (42.0 mg, 43%, purity ca. 95%). This compound was characterized as a
1
1
mixture of two diastereomers (1.9:1 by H NMR analysis): TLC Rf 0.47 (hexane/EtOAc 20:1); H NMR
(600 MHz, CDCl3) δ 0.82-0.90 (m, 3H), 1.05-1.46 (m, 14H), 3.05 (t, J = 10.6 Hz, 1H, minor
diastereomer), 3.31 (t, J = 3.4 Hz, 1H, major diastereomer), 3.33-3.38 (m, 1H, major diastereomer),
3.45-3.53 (m, 1H, minor diastereomer), 4.15 (d, J = 10.6 Hz, 1H, minor diastereomer), 4.30 (d, J = 3.4 Hz,
1H, major diastereomer), 6.36 (dd, J = 10.3, 2.4 Hz, 1H, minor diastereomer), 6.63 (dd, J = 9.6, 2.8 Hz,
13
1H, major diastereomer), 6.76-7.28 (m, 10H); C NMR (100 MHz, CDCl3) major diastereomer: δ 14.1,
22.6, 27.1, 29.1, 29.2, 29.3, 31.7, 32.1, 40.5, 50.0, 50.7, 115.0 (d, J = 21.6 Hz), 118.4 (d, J = 21.5 Hz),
127.7 (d, J = 7.2 Hz), 128.3, 128.6, 128.8, 129.9, 130.5, 132.6, 133.0, 134.8 (d, J = 5.7 Hz), 138.6, 143.9,
160.2 (d, J = 242.7 Hz), and minor diastereomer (selected): δ 26.2, 29.1, 31.8, 33.7, 46.5, 54.0, 55.5,
114.2 (d, J = 23.0 Hz), 117.1 (d, J = 23.0 Hz), 128.5 (d, J = 7.2 Hz), 129.3, 129.7, 132.4 (d, J = 10.1 Hz),
139.7 (d, J = 5.7 Hz), 140.8, 141.7; IR (neat) 2926, 1491, 1094 cm-1; LRMS (EI) m/z 500 (M+); HRMS
(EI) calcd for C29H31Cl2FS (M+) 500.1508, found 500.1509.
6-Fluoro-2,3-bis-(2-methoxyphenyl)-4-octylthiochroman (3e). Prepared from ArSSAr (Ar = p-FC6H4)

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HETEROCYCLES, Vol. 76, No. 2, 2008
(256.4 mg, 1.01 mmol), 1-methoxy-1-(4-fluorophenylthio)nonane (1a) (87.5 mg, 0.308 mmol) and
1
trans-2,2’-dimethoxystilbene (47.8 mg, 0.199 mmol). The H NMR analysis of the crude product
indicated that the title compound was formed in 53% yield (Cl2CHCHCl2 was used as an internal
1
standard): TLC Rf 0.33 (hexane/EtOAc 20:1); H NMR (400 MHz, CDCl3) δ 0.84 (t, J = 6.8 Hz, 3H),
1.00-1.58 (m, 14H), 3.35-3.41 (m, 1H), 3.81 (s, 3H), 3.86 (s, 3H), 4.19 (dd, J = 4.8, 3.6 Hz, 1H), 4.75 (d,
13
J = 4.8 Hz, 1H), 6.58 (dd, J = 10.2, 2.4 Hz, 1H), 6.72-6.90 (m, 6H), 7.11-7.18 (m, 4H); C NMR (100
MHz, CDCl3) δ 14.2, 22.8, 27.6, 29.3, 29.49, 29.51, 31.4, 31.9, 38.7, 42.2, 42.6, 55.4, 55.6, 110.2, 110.3,
113.9 (d, J = 21.9 Hz), 118.1 (d, J = 21.4 Hz), 120.1, 120.3, 127.2, 127.3, 127.4, 129.1, 129.6, 129.8 (d, J
= 2.8 Hz), 129.9, 134.1, 137.2 (d, J = 6.7 Hz), 156.1, 157.1, 159.9 (d, J = 240.0 Hz); IR (neat) 2926, 1599,
1242 cm-1; LRMS (EI) m/z 492 (M+); HRMS (EI) calcd for C31H37FO2S (M+) 492.2498, found 492.2494.
6-Fluoro-2,3,4-triphenylthiochroman (3f). Prepared from ArSSAr (Ar = p-FC6H4) (255.8 mg, 1.01
mmol), methyl phenyl(4-fluorophenylthio)methyl ether (77.9 mg, 0.314 mmol) and cis-stilbene (35.1 mg,
0.195 mmol) and purified by flash chromatography (hexane/EtOAc 20:1) and purified by GPC (41.2 mg,
53%). This compound was characterized as a mixture of two diastereomers (>15:1 by 1H NMR analysis):
TLC Rf 0.39 (hexane/EtOAc 20:1); 1H NMR (400 MHz, CDCl3) δ 3.65 (t, J = 10.8 Hz, 1H), 4.41 (d, J =
13
10.8 Hz, 1H), 4.66 (d, J = 10.8 Hz, 1H), 6.49 (ddd, J = 10.6, 2.6, 1.2 Hz, 1H), 6.72-7.20 (m, 17H); C
NMR (100 MHz, CDCl3) major diastereomer: δ 51.3, 54.9, 56.4, 113.9 (d, J = 22.3 Hz), 117.5 (d, J =
22.3 Hz), 126.0, 126.3, 127.3, 127.6 (d, J = 7.5 Hz), 127.8, 128.12, 128.15, 128.19, 128.19, 129.1, 129.3
(d, J = 2.7 Hz), 139.2, 140.4 (d, J = 6.7 Hz), 141.2, 143.2, 160.0 (d, J = 241.2 Hz); IR (KBr) 1601, 1474,
696 cm-1; LRMS (EI) m/z 396 (M+); HRMS (EI) calcd for C27H21FS (M+) 396.1348, found 396.1349.
4-(4-Chlorophenyl)-6-fluoro-2,3-diphenylthiochroman (3g). Prepared from ArSSAr (Ar = p-FC6H4)
(256.6 mg, 1.01 mmol), methyl 4-chlorophenyl(4-fluorophenylthio)methyl ether (88.9 mg, 0.314 mmol)
and cis-stilbene (36.9 mg, 0.205 mmol) and purified by flash chromatography (hexane/EtOAc 20:1) and
purified by GPC (59.5 mg, 67%). This compound was characterized as a mixture of two diastereomers
(2.2:1 by 1H NMR analysis): TLC Rf 0.32 (hexane/EtOAc 20:1); 1H NMR (400 MHz, CDCl3) δ 3.61 (t, J
= 10.8 Hz, 1H), 4.41 (d, J = 10.8 Hz, 1H), 4.67 (d, J = 10.8 Hz, 1H), 6.46-7.22 (m, 17H); 13C NMR (100
MHz, CDCl3) major diastereomer: δ 50.6, 54.8, 56.4, 114.0 (d, J = 21.8 Hz), 117.6 (d, J = 22.2 Hz), 126.3,
126.4, 127.5 (d, J = 7.5 Hz), 128.0, 128.09, 128.16, 128.19, 128.3, 129.1, 129.5, 130.4, 132.9, 137.8,
140.9, 143.0, 160.1 (d, J = 241.6 Hz), and minor diastereomer (selected): δ 51.2, 54.3, 56.5, 114.1 (d, J =
21.8 Hz), 117.4 (d, J = 22.2 Hz), 128.4, 138.9, 140.28, 140.35, 160.0 (d, J = 241.6 Hz); IR (KBr) 1601,
1453, 698 cm-1; LRMS (EI) m/z 430 (M+); HRMS (EI) calcd for C27H20ClFS (M+) 430.0958, found
430.0955.
4-Cyclohexyl-6-fluoro-2,3-diphenylthiochroman (3h). Prepared from ArSSAr (Ar = p-FC6H4) (255.4

HETEROCYCLES, Vol. 76, No. 2, 2008
1115
mg, 1.00 mmol), methyl cyclohexyl(4-fluorophenylthio)methyl ether (77.7 mg, 0.305 mmol) and
cis-stilbene (36.2 mg, 0.201 mmol) and purified by flash chromatography (hexane/EtOAc 20:1) and
purified by GPC (30.0 mg, 37%). This compound was characterized as a mixture of two diastereomers
(2.4:1 by 1H NMR analysis): TLC Rf 0.38 (hexane/EtOAc 20:1); 1H NMR (600 MHz, CDCl3) δ 0.65-1.88
(m, 1H), 3.22-3.30 (m, 1H), 3.53-3.60 (m, 1H), 4.21 (d, J = 10.7 Hz, 1H, major diastereomer), 4.30 (d, J
= 2.0 Hz, 1H, minor diastereomer), 6.40 (dd, J = 10.3, 2.8 Hz, 1H, major diastereomer), 6.65 (dd, J = 9.6,
2.8 Hz, 1H, minor diastereomer), 6.79-7.33 (m, 12H); 13C NMR (150 MHz, CDCl3) major diastereomer:
δ 26.0, 26.3, 26.3, 26.5, 32.1, 39.9, 53.0, 53.9, 55.0, 113.8 (d, J = 21.5 Hz), 116.8 (d, J = 21.5 Hz), 126.3,
128.15, 128.20, 128.25, 128.3, 128.5, 129.3, 129.4, 142.8, 142.9, 160.3 (d, J = 241.3 Hz), and minor
diastereomer (selected): δ 25.5, 25.7, 26.2, 30.7, 31.1, 38.6, 45.7, 46.8, 53.3, 114.7 (d, J = 21.6 Hz), 118.4
(d, J = 21.6 Hz), 130.9, 134.6, 140.8, 145.3, 160.1 (d, J = 241.3 Hz); IR (KBr) 1476, 1264, 700 cm-1;
LRMS (EI) m/z 402 (M+); HRMS (EI) calcd for C27H27FS (M+) 402.1818, found 402.1819.
6-Fluoro-2,3-diphenyl-4-(2-phenylethyl)thiochroman (3i). Prepared from ArSSAr (Ar = p-FC6H4)
(254.4 mg, 1.00 mmol), methyl 2-phenylethyl(4-fluorophenylthio)methyl ether (83.2 mg, 0.301 mmol)
and cis-stilbene (36.4 mg, 0.202 mmol) and purified by flash chromatography (hexane/EtOAc 20:1) and
purified by GPC (52.1 mg, 61%). This compound was characterized as a mixture of two diastereomers
1
(3.8:1 by 1H NMR analysis): TLC Rf 0.39 (hexane/EtOAc 20:1); H NMR (400 MHz, CDCl3) δ 1.50-1.66
(m, 1H), 1.72-1.84 (m, 1H), 2.52-2.84 (m, 2H), 3.15 (t, J = 10.4 Hz, 1H, minor diastereomer), 3.40-3.50
(m, 2H, major diastereomer), 3.54 (dt, J = 10.4, 3.2 Hz, 1H, minor diastereomer), 4.17 (d, J = 10.4 Hz,
13
1H, minor diastereomer), 4.39 (d, J = 3.6 Hz, 1H, major diastereomer), 6.38-7.30 (m, 17H); C NMR
(100 MHz, CDCl3) major diastereomer: δ 33.3, 34.0, 39.9, 50.4, 51.3, 114.5 (d, J = 22.2 Hz), 118.4 (d, J
= 21.4 Hz), 125.7, 126.5, 127.0, 127.4 (d, J = 7.6 Hz), 128.1, 128.2, 128.4, 128.5, 129.1, 135.4, 135.6,
140.1, 140.8, 141.0, 145.6, 160.0 (d, J = 241.6 Hz), and minor diastereomer (selected): δ 32.5, 35.6, 54.7,
55.9, 113.8 (d, J = 21.9 Hz), 117.2 (d, J = 22.2 Hz), 126.3, 128.2, 129.2, 143.1, 143.0; IR (neat) 3004,
1601, 1495 cm-1; LRMS (EI) m/z 424 (M+); HRMS (EI) calcd for C29H25FS (M+) 424.1661, found
424.1661.
4-Octyl-2,3-diphenylthiochroman (3j). Prepared from PhSSPh (222.4 mg, 1.02 mmol),
1-methoxy-1-phenylthiononane (83.2 mg, 0.312 mmol) and cis-stilbene (36.6 mg, 0.203 mmol) and
purified by flash chromatography (hexane/EtOAc 20:1) and purified by GPC (23.4 mg, 28%). This
compound was characterized as a mixture of two diastereomers (2.6:1 by 1H NMR analysis): TLC Rf 0.37
1
(hexane/EtOAc 20:1); H NMR (400 MHz, CDCl3) δ 0.84 (t, J = 7.2 Hz, 3H, major diastereomer), 0.85 (t,
J = 6.8 Hz, 3H, minor diastereomer), 1.00-1.48 (m, 14H), 3.15 (t, J = 10.4 Hz, 1H, minor diastereomer),
3.60 (t, J = 3.2 Hz, 1H, major diastereomer), 3.42-3.50 (m, 1H, major diastereomer), 3.56-3.64 (m, 1H,

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HETEROCYCLES, Vol. 76, No. 2, 2008
minor diastereomer), 4.25 (d, J = 10.4 Hz, 1H, minor diastereomer), 4.41 (d, J = 3.2 Hz, 1H, major
13
diastereomer), 6.65-7.29 (m, 14H); C NMR (100 MHz, CDCl3) major diastereomer: δ 14.2, 22.8, 27.3,
29.2, 29.42, 29.44, 31.9, 32.7, 40.2, 50.8, 51.4, 124.3, 126.0, 126.2, 126.6, 126.7, 127.9, 128.3, 128.6,
129.2, 132.1, 133.4, 134.9, 140.6, 146.6, and minor diastereomer (selected): δ 26.4, 29.3, 29.4, 31.9, 33.8,
46.5, 54.6, 56.2, 124.2, 125.9, 126.1, 126.2, 127.9, 128.10, 128.12, 129.2, 130.7, 138.3, 142.5, 144.2; IR
(neat) 2926, 1453, 700 cm-1; LRMS (EI) m/z 414 (M+); HRMS (EI) calcd for C29H34S (M+) 414.2381,
found 414.2379.
6-Chloro-4-octyl-2,3-diphenylthiochroman (3k). Prepared from ArSSAr (Ar = p-ClC6H4) (287.9 mg,
1.00 mmol), 1-methoxy-1-(4-chlorophenylthio)nonane (90.9 mg, 0.302 mmol) and cis-stilbene (35.9 mg,
0.199 mmol) and purified by flash chromatography (hexane/EtOAc 20:1) and purified by GPC (66.4 mg,
74%). This compound was characterized as a mixture of two diastereomers (3.1:1 by 1H NMR analysis):
TLC Rf 0.29 (hexane/EtOAc 20:1); 1H NMR (400 MHz, CDCl3) δ 0.81-0.87 (m, 3H), 1.00-1.50 (m, 14H),
3.11 (t, J = 10.4 Hz, 1H, minor diastereomer), 3.34 (t, J = 3.2 Hz, 1H, major diastereomer), 3.40-3.48 (m,
1H, major diastereomer), 3.52-3.60 (m, 1H, minor diastereomer), 4.19 (d, J = 10.4 Hz, 1H, minor
13
diastereomer), 4.36 (d, J = 3.2 Hz, 1H, major diastereomer), 6.65-7.30 (m, 13H); C NMR (100 MHz,
CDCl3) major diastereomer: δ 14.2, 22.7, 27.2, 29.2, 29.3, 29.4, 31.86, 31.91, 32.6, 40.3, 50.4, 51.4,
126.5, 126.9, 127.0, 127.2, 128.0, 128.4, 128.5, 129.1, 129.6, 131.7, 133.6, 135.2, 140.23, 145.8, and
minor diastereomer (selected): δ 26.3, 29.3, 31.9, 33.8, 46.7, 54.5, 56.0, 126.2, 126.36, 126.39, 128.1,
128.2, 129.1, 129.8, 130.3, 132.1, 140.2, 142.2, 143.2; IR (neat) 2926, 1468, 1103 cm-1; LRMS (EI) m/z
448 (M+); HRMS (EI) calcd for C29H33ClS (M+) 448.1992, found 448.1981.
6-Methyl-4-octyl-2,3-diphenylthiochroman (3l). Prepared from ArSSAr (Ar = p-MeC6H4) (250.7 mg,
1.02 mmol), 1-methoxy-1-(4-methylphenylthio)nonane (82.4 mg, 0.294 mmol) and cis-stilbene (36.0 mg,
0.200 mmol) and purified by flash chromatography (hexane/EtOAc 20:1) and purified by GPC (27.6 mg,
32%, purity ca. 85%). This compound was characterized as a mixture of two diastereomers (2.4:1 by 1H
1
NMR analysis): TLC Rf 0.36 (hexane/EtOAc 20:1); H NMR (400 MHz, CDCl3) δ 0.80-0.88 (m, 3H),
1.00-1.48 (m, 14H), 2.10 (s, 3H, minor diastereomer), 2.17 (s, 3H, major diastereomer), 3.12 (t, J = 10.0
Hz, 1H, minor diastereomer), 3.32 (t, J = 2.8 Hz, 1H, major diastereomer), 3.42-3.48 (m, 1H, major
diastereomer), 3.50-3.58 (m, 1H, minor diastereomer), 4.21 (d, J = 10.0 Hz, 1H, minor diastereomer),
4.36 (d, J = 2.8 Hz, 1H, major diastereomer), 6.51 (br s, 1H, minor diastereomer), 6.73-6.76 (m, 1H,
major diastereomer), 6.80-7.30 (m, 12H); 13C NMR (100 MHz, CDCl3) major diastereomer: δ 14.2, 21.0,
22.8, 27.2, 29.2, 29.40, 29.44, 31.9, 32.9, 40.0, 50.9, 51.5, 125.8, 126.1, 126.7, 127.7, 127.9, 128.1, 128.2,
128.6, 129.2, 132.7, 133.1, 133.8, 140.7, 146.8, and minor diastereomer (selected): δ 21.0, 26.5, 29.3,
29.4, 29.8, 31.9, 33.8, 46.7, 54.7, 56.9, 125.8, 126.2, 126.9, 127.1, 127.8, 129.2, 130.0, 131.2, 131.3,

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133.9, 138.2, 142.8, 144.3; IR (neat) 2924, 1453, 700 cm-1; LRMS (EI) m/z 428 (M+); HRMS (EI) calcd
for C30H36S (M+) 428.2538, found 428.2537.
ACKNOWLEDGEMENTS
This work was financially supported in part by a Grant-in-Aid for Scientific Research from the Japan
Society for the Promotion of Science. We are also grateful to Nippon Shokubai Co. and Nippoh
Chemicals Co. for providing sodium tetrakis(pentafluorophenyl)borate as a precursor of Bu4NB(C6F5)4.
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