Enantioselective hydrogen atom transfer to α-sulfonyl radicals controlled by selective coordination of a chiral Lewis acid to an enantiotopic sulfonyl oxygen

Article abstract of DOI:10.1016/S0957-4166(03)00531-7

Enantioselective hydrogen atom transfer to α-sulfonyl radicals generated from the alkyl radical addition to 2-propenyl and 1-phenylethenyl sulfones in the presence of chiral Lewis acids affords products with high enantioselectivity. The stereochemical course is discussed with the transition states involving selective coordination of a chiral Lewis acid to an enantiotopic sulfonyl oxygen.

Full text of DOI:10.1016/S0957-4166(03)00531-7

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 14 (2003) 3043–3055
Enantioselective hydrogen atom transfer to a-sulfonyl radicals
controlled by selective coordination of a chiral Lewis acid to an
enantiotopic sulfonyl oxygen
Hideki Sugimoto, Shuichi Nakamura, Yoshihiko Watanabe† and Takeshi Toru*
Department of Applied Chemistry, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555, Japan
Received 28 April 2003; accepted 29 May 2003
Abstract—Enantioselective hydrogen atom transfer to a-sulfonyl radicals generated from the alkyl radical addition to 2-propenyl
and 1-phenylethenyl sulfones in the presence of chiral Lewis acids affords products with high enantioselectivity. The stereochem-
ical course is discussed with the transition states involving selective coordination of a chiral Lewis acid to an enantiotopic sulfonyl
oxygen.
© 2003 Elsevier Ltd. All rights reserved.
1. Introduction
Indeed, we recently communicated a highly enantiose-
lective radical allylation of the a-sulfonyl radical in the
presence of a chiral Lewis acid prepared from Zn(OTf)2
and bis(oxazoline).6 We now report a highly enantiose-
lective hydrogen atom transfer to a-sulfonyl radicals
using the benzimidazolyl sulfonyl group as a stereo-
inducer.
Free radical reactions are powerful and versatile tools
for carbonꢀcarbon bond formations. High diastereose-
lectivity has been observed in both substrate- and auxil-
iary-controlled reactions.1 Sulfoxides have been widely
used as important chiral auxiliaries in asymmetric radi-
cal reactions.2 On the other hand, the sulfonyl group is
achiral in itself, but has prochiral oxygens. Studies on
asymmetric reactions focusing on prochiral sulfonyl
oxygens are extremely attractive, but the application of
sulfonyl compounds to enantioselective reactions has
been limited.3 We have reported a highly diastereoselec-
tive radical reaction of a-sulfonyl radicals specifically
coordinated to prochiral sulfonyl oxygens controlled by
intramolecular hydrogen bonding and chelation with
Lewis acids.4 From these results, we envisaged that a
stereogenic sulfur newly created by enantioselective
coordination to one of the sulfonyl oxygens would
control the enantioselective radical reaction (Fig. 1).5
2. Results
Scheme 1 illustrates the preparation of various vinyl
sulfones 6a–g which were subjected to enantioselective
radical addition-hydrogen atom transfer reactions. N-
Arylmethylation or N-methylation of sulfides of 1 and
2 afforded sulfides 3a–g (method A or B), which were
oxidized with m-CPBA giving sulfones 4a–g in high
yields. Selenosulfones 5a,d–g (method C) were prepared
on treatment of the corresponding sulfones 4a,d–g with
2 equiv. of LHMDS and subsequently with phenylse-
lenyl bromide, whereas selenosulfones 5b,c were
obtained on treatment of 4b,c with 2 equiv. of LDA
and diphenyl diselenide (method D).7 Oxidation of 5a–g
with m-CPBA at 0°C followed by warming the mixture
gave vinylsulfones 6a–g.
We first examined the hydrogen atom transfer to the
a-sulfonyl radical generated from the addition of a
tert-butyl radical to 2-propenyl sulfones 6a–d. The
addition-hydrogen atom transfer to 6a–d was carried
out by treatment with tert-butyl iodide (2 equiv.), tri-
butyltin hydride (2 equiv.), and triethylborane (2 equiv.)
Figure 1. Asymmetric induction through the sulfonyl group.
* Corresponding author. Tel.: 81-52-735-5217; fax: 81-52-735-5217;
e-mail: toru@ach.nitech.ac.jp
† Deceased, June 23, 2001.
0957-4166/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0957-4166(03)00531-7

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H. Sugimoto et al. / Tetrahedron: Asymmetry 14 (2003) 3043–3055
Scheme 1. Reagents and conditions: (a) (A): arylmethyl halides, KOH, THF, reflux, or (B): methyl iodide, n-BuLi, THF, 0°C“rt;
(b) m-CPBA, CH2Cl2, 0°C“rt; (c) (C): LHMDS, HMPA, PhSeBr, THF, −78°C“rt, or (D): LDA, HMPA, (PhSe)2, THF,
−78°C“rt; (d) m-CPBA, CH2Cl2, 0°C“rt.
in the presence of a chiral Lewis acid (1 equiv.). The
results are shown in Table 1.8 No addition-hydrogen
atom transfer product 7a was obtained using the chiral
Lewis acid derived from Cu(OTf)2 and bis(oxazoline)-
Ph 8 (entry 1), whereas the reaction in the presence of
ZnBr2-bis(oxazoline)-Ph 8 afforded the product 7a in
high yield but with no enantioselectivity (entry 2). The
reaction using Zn(OTf)2 as a Lewis acid gave 7a with
good enantioselectivity (entry 3). The addition-hydro-
gen atom transfer in the presence of Mg(ClO4)2-8 or
Mg(OTf)2-8 did not improve the enantioselectivity
(entries 4 and 5). Bis(oxazoline)-Ph 8 gave the best
stereoselectivity with Zn(OTf)2 among other bis(oxazo-
line)s 9, 10, 11, 12,9 1310 (entries 6–10). So it was with
N-(3,5-dimethylphenyl)methyl sulfone 6b. The reaction
of 6d with Zn(OTf)2-bis(oxazoline)-Ph 8 gave 7d in 97%
yield with 82% ee (entry 11). The reaction of N-(2,4,6-
trimethylphenyl)methyl sulfone 6c and N-methyl sul-
fone 6d afforded the products 7c and 7d with lower
enantioselectivity in comparison with that from N-ben-
zyl sulfone 6a (entries 12 and 13 versus entry 3).
with low enantioselectivity (entry 4 and entry 5). In the
reaction with several alkyl radicals using a Zn(OTf)2-
bis(oxazoline)-Ph complex and tributyltin hydride, the
addition-hydrogen atom transfer to 6a with ethyl, iso-
propyl and c-hexyl radicals afforded the products 14–
16 (entries 7–9) in high yields but with low
enantioselectivity. These results suggest that the
stereoselectivity obtained depends on the steric bulki-
ness of the alkyl radicals and the tin reagents.
The absolute configuration of 7a was determined as
follows (Scheme 2): Treatment of (S)-4,4-dimethyl-2-
pentanol11 17 with triphenylphosphine and 1-benzyl-
benzimidole-2-thiol12 gave (R)-sulfide 18 with 95% ee.13
(R)-Sulfide 18 was oxidized with m-CPBA to afford
sulfone (R)-7a quantitatively with 95% ee. The stereo-
chemistry of the product 7a formed in the enantioselec-
tive hydrogen atom transfer to the a-sulfonyl radical
was determined to be S in comparison with the specific
rotation. The absolute configuration of 7b was deduced
to be S.
Table 2 shows the results obtained in the reaction using
various hydrogen atom donors and alkyl halides. When
an excess amount of tributyltin hydride was used, the
hydrogenated product was formed in 19% yield with
39% ee (entry 2), and the enantioselectivity was
decreased (entry 1). The reaction using tributyltin deu-
teride proceeded sluggishly, and formation of the
deuterated product was not observed. The reaction
using triphenyltin hydride proceeded slowly (entry 3).
The reaction using trimethytin hydride as a less hin-
dered hydride afforded the product 7a in high yield but
Next, we examined the addition-hydrogen atom trans-
fer to 1-phenylethenyl sulfones 6e–g. The results are
shown in Table 3.14 Surprisingly, the reaction of 6e–g
with tert-butyl iodide, tributyltin hydride, and triethyl
borane in the presence of Zn(OTf)2-bis(oxazoline)-Ph 8
did not afford the addition hydrogen atom transfer
product 7 at all, whereas the reaction with ethyl iodide
proceeded smoothly. Thus, the reaction of N-benzyl-
benzimidazolyl sulfone 6e with 2 equiv. of ethyl iodide,
2 equiv. of tributyltin hydride, and 4 equiv. of triethyl

H. Sugimoto et al. / Tetrahedron: Asymmetry 14 (2003) 3043–3055
3045
Table 1. Addition-hydrogen atom transfer to 2-propenyl sulfones 6a–d with various chiral ligands
Entry
Vinyl sulfone
R1
Lewis acid
Ligand
Time (min)
Product
Yield (%)
Ee (%)a
1
2
3
4
5
6
7
8
6a
6a
6a
6a
6a
6a
6a
6a
6a
6a
6b
6c
6d
C6H5CH2
C6H5CH2
C6H5CH2
C6H5CH2
C6H5CH2
C6H5CH2
C6H5CH2
C6H5CH2
C6H5CH2
C6H5CH2
3,5-Me2C6H3CH2
2,4,6-Me3C6H2CH2
Me
Cu(OTf)2
ZnBr2
8
8
8
8
8
360
30
60
60
60
30
30
60
60
60
60
90
60
7a
7a
7a
7a
7a
7a
7a
7a
7a
7a
7b
7c
7d
Trace
95
88
97
94
99
98
98
98
99
97
95
99
–
0
Zn(OTf)2
Mg(ClO4)2
Mg(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
56
27
0
9
1
5
10
11
12
13
8
4
9
2
10
11
12
13
6
82
5
8
8
26
a Ee was determined by HPLC analysis using CHIRALCEL® OD-H.
Table 2. Addition-hydrogen atom transfer to 2-propenyl sulfone 6a with various hydrogen atom donors
Entry
R
Hydrogen atom donor (equiv.)
Time (min)
Product
Yield (%)
Ee (%)a
1
2
3
4
5
6
7
8
9
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
Et
Bu3SnH (10)
Bu3SnD (4)
Ph3SnH (2)
Me3SnH (2)
Me3SnH (10)
(TMS)3SiH (2)
Bu3SnHc (2)
Bu3SnHc (2)
Bu3SnHc (2)
10
2 days
360
60
15
1 week
210
90
7a
7a
7a
7a
7a
7a
14
15
16
98
19b
8
99
98
35
79
89
74
20
39
38
36
38
0
5
24
8
i-Pr
c-Hex
210
a Ee was determined by HPLC analysis.
b The yield of hydrogenated product. The deuterated product was not formed.
c RI (4 equiv.), Bu3SnH (4 equiv.), and Et3B (4 equiv.) were used.

3046
H. Sugimoto et al. / Tetrahedron: Asymmetry 14 (2003) 3043–3055
showed almost no enantioselectivity (entries 5 and 6).
Other bis(oxazoline)s 9–12 did not improve the enan-
tioselectivity (entries 7–10). The reaction using 10
equiv. of tributyltin hydride proceeded rapidly to give
6e with enantioselectivity as high as that obtained in the
reaction using 2 equiv. of tributyltin hydride (entry 11).
Notably, when triphenyltin hydride and tris(trimethylsi-
lyl)silane were used as hydrogen donors, the reaction
proceeded slowly, but the enantioselectivities were sub-
stantially the same as that obtained with tributyltin
hydride (entries 12 and 13 versus entry 3).
The stereochemistry of 7g was determined by stereospe-
cific transformation from (R)-1-phenyl-1-butanol15 19
as shown in Scheme 3. (R)-19 was subjected to the
Mitsunobu reaction to give (S)-benzimidazolyl sulfide
(S)-20 which was transformed to (S)-benzimidazolyl
sulfone (S)-7g. By comparison of specific rotations, the
absolute configuration of 7g formed from sulfone 6g
was deduced to be R.
Scheme 2.
borane gave 7e in high yield, but, unfortunately, HPLC
analysis of 7e with various chiral columns failed to
determine the enantioselectivity. The reaction of N-
(3,5-dimethyphenyl)methylbenzimidazolyl sulfone 6f
gave the product 7f with 68% ee (entry 2). On the other
hand, N-methylbenzimidazolyl sulfone 6g showed high
enantioselectivity. Thus, the addition of an ethyl radical
and hydrogen atom transfer from tributyltin hydride in
the presence of Zn(OTf)2-bis(oxazoline)-Ph 8 gave 7g in
high yield with 91% ee (entry 3). The reaction using a
catalytic amount of Zn(OTf)2-8 gave 7g with good
enantioselectivity (entry 4). Mg(ClO4)2-8 or Mg(OTf)2-8
3. Discussion
We assumed the reaction mechanism involved the radi-
cal hydrogen atom transfer to 2-propenyl sulfone 6a.
Previously, we have reported that the reaction of vinyl
sulfone 21 with tert-butyl iodide and triethyl borane in
the presence of Zn(OTf)2 and bis(oxazoline)-Ph formed
the carbon radical which was trapped with diallyl-
Table 3. Addition-hydrogen atom transfer to 1-phenylethenyl sulfones 6e–g
Entry
Vinyl sulfone
Lewis acid
Zn(OTf)2
Ligand
Hydrogen atom Time (min)
donor (equiv.)
Product
Yield (%)
Ee (%)a
R
1
2
3
4
5
6
7
8
6e
6f
C6H5CH2
3,5-Me2C6H3CH2 Zn(OTf)2
8
8
8
8
8
8
9
10
11
12
8
Bu3SnH (2)
Bu3SnH (2)
Bu3SnH (2)
Bu3SnH (2)
Bu3SnH (2)
Bu3SnH (2)
Bu3SnH (2)
Bu3SnH (2)
Bu3SnH (2)
Bu3SnH (2)
Bu3SnH (10)
Ph3SnHc (2)
120
120
120
120
120
120
120
120
120
120
30
7e
7f
85
75
99
67
68
77
99
99
76
65
64
55
25
–
68
91
55
0
4
0
17
16
35
91
93
89
6g
6g
6g
6g
6g
6g
6g
6g
6g
6g
6g
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Zn(OTf)2
Zn(OTf)2
7g
7g
7g
7g
7g
7g
7g
7g
7g
7g
7g
b
Mg(OTf)2
Mg(OCl4)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
9
10
11
12
13
8
8
360
(TMS)3SiHd (4) 1 week
a Ee was determined by HPLC analysis using CHIRALCEL® OD-H.
b Zn(OTf)2 (0.3 equiv.) and 8 (0.3 equiv.) were used.
c EtI (2 equiv.), Ph3SnH (2 equiv.), and Et3B (6 equiv.) were used.
d EtI (2 equiv.), (TMS)3SiH (4 equiv.), and Et3B (4 equiv.) were used.

H. Sugimoto et al. / Tetrahedron: Asymmetry 14 (2003) 3043–3055
3047
dibutyltin to give (S)-benzimidazolyl sulfone 22 with
high enantioselectivity. Surprisingly, in this reaction,
diallyldibutyltin approaches the Si face of the carbon
radical from the direction opposite to the direction
from which the tin hydride approaches the radical
center generated in the reaction of 6a (Scheme 4). The
opposite stereochemical course16 in the allylation and
the hydrogen atom transfer to similar a-sulfonyl radi-
cals could not be explained by the difference in stability
of the radical intermediates. Therefore, the obtained
stereoselectivity should be discussed with the stability of
the transition states involving an interaction between
the carbon radical and the hydrogen atom donor.
The plausible transition states for both reactions are
shown in Figs. 2 and 3. The radical allylation and
hydrogen atom transfer using the same chiral Lewis
acid would proceed through transition states having
tetrahedral zinc, chelating between the sulfonyl oxygen
and the nitrogen atom in the benzimidazolyl group.17
The pro-R oxygen of the sulfonyl group preferably
coordinates with cationic zinc because of the steric
repulsion between the neopentyl and the phenyl groups
on the bis(oxazoline) ring. The bulkiest benzimidazolyl
group occupies the open space. The second bulkiest
group is supposed to be tributyltin hydride which
approaches from the direction antiperiplanar to the
benzimidazolyl group. A linear CꢀHꢀSn geometry is
preferable in the intermolecular hydrogen atom transfer
from Bu3SnH.18 On the other hand, in the allylation of
the a-sulfonyl radical derived from 21, the neopentyl
group is supposed to occupy the position antiperiplanar
to the benzimidazolyl group and diallyldibutyltin
approaches the Si face to form (S)-22 through an SH2%
pathway (Fig. 3).19
Scheme 3.
It is not clear why 1-phenylethenyl sulfone 6g showed
higher enantioselectivity than 2-propenyl sulfone 6b. It
is surprising that a large excess amount of tributyltin
hydride and hydrogen atom donors with low reactivity,
the latter of which needed prolonged reaction time to
complete the reaction, showed substantially the same
high enantioselectivity as tributyltin hydride showed
(Table 3, entries 11 and 12 versus entry 3). These results
indicate that the stable chelating intermediate is
formed. A plausible transition state forming (R)-7g
through a considerably stabilized carbon radical adja-
cent to the phenyl group is depicted in Figure 4.
Scheme 4.
Figure 2. Plausible transition state for the hydrogen atom transfer to a-sulfonyl radical derived from 6a.

3048
H. Sugimoto et al. / Tetrahedron: Asymmetry 14 (2003) 3043–3055
Figure 3. Plausible transition state for the allylation a-sulfonyl radical derived from 21.
Figure 4. Plausible transition state for the hydrogen atom transfer to a-sulfonyl radical derived from 6g.
4. Conclusion
bined extracts were dried over Na2SO4 and concen-
trated under reduced pressure to leave a solid which
was washed with hexane (30 mL) to afford 3a (4.02 g,
87%): mp 126.4–127.1°C, Rf=0.38 (hexane/ethyl acet-
Hydrogen atom transfer to a-sulfonyl radicals gener-
ated from the alkyl radical addition to 2-propenyl and
1-phenyletheny sulfones in the presence of a chiral
Lewis acid afforded the addition-hydrogen atom trans-
fer products with high enantioselectivity. The stereo-
chemical courses of these reactions were elucidated with
the assumed transition state involving selective coordi-
nation of a chiral Lewis acid to one of the enantiotopic
sulfonyl oxygens. The use of achiral sulfonyl groups as
stereo-inducers has significant potential for further
extension to asymmetric reactions. Currently, studies
are in progress in this direction.
1
ate=80/20); H NMR l 1.47 (d, J=6.8 Hz, 6H), 4.15
(sep, J=6.8 Hz, 1H), 5.33 (s, 2H), 7.17–7.28 (m, 8H),
7.68–7.79 (m, 1H); 13C NMR l 23.5, 38.9, 47.5, 109.2,
118.4, 121.9, 122.0, 126.8, 126.9, 127.8, 128.8, 135.83,
143.8, 151.8; IR (KBr) 3023, 2969, 1458, 1421, 1376,
1346, 1241, 741, 722 cm−1; EIMS m/z (rel. intensity)
282 (M+, 18), 240 (30), 207 (25), 91 (100). Anal calcd
for C17H18N2S; C, 72.30, H, 6.42, N, 9.92. Found: C,
72.32, H, 6.55, N, 9.77.
5.2. 1-[(3,5-Dimethylphenyl)methyl]-2-[(1-methyethyl)-
thio]benzimidazole, 3b
5. Experimental
The reaction was carried out as described above except
for using 1 (1.51 g, 7.85 mmol), potassium hydroxide
(673 mg, 10.2 mmol) and (3,5-dimethylphenyl)methyl
bromide (1.72 g, 8.64 mmol) in THF (30.0 mL) was
heated under reflux for 12 h. Work-up as above gave a
solid which was purified by column chromatography
(silica gel 70 g, hexane/ethyl acetate=95/5) to afford 3b
(1.97 g, 81%): Rf=0.21 (hexane/ethyl acetate=95/5);
1H NMR l 1.48 (d, J=6.8 Hz, 6H), 2.25 (s, 6H), 4.16
5.1. 2-[(1-Methylethyl)thio]-1-(phenylmethyl)benz-
imidazole, 3a
A mixture of 2-(1-methylthio)benzimidazole 1 (3.16 g,
16.4 mmol), potassium hydroxide (1.40 g, 21.3 mmol)
and benzyl chloride (2.27 mL, 19.7 mol) in THF (30.0
mL) was heated under reflux for 1 h. After cooling,
water was added and extracted with CH2Cl2, the com-

H. Sugimoto et al. / Tetrahedron: Asymmetry 14 (2003) 3043–3055
3049
1
(sep, J=6.8 Hz, 1H), 5.25 (s, 2H), 6.77 (s, 2H), 6.89 (s,
1H), 7.10–7.35 (m, 3H), 7.64–7.83 (m, 1H); 13C NMR l
21.4, 23.6, 39.0, 47.6, 109.2, 118.1, 121.7, 121.8, 124.4,
129.2, 135.4, 138.1, 143.3, 151.5; IR (neat) 2965, 2921,
1429, 1365, 1242, 741 cm−1; EIMS m/z (rel. intensity)
310 (M+, 32), 268 (36), 235 (24), 119 (55), 86 (29), 84
(45), 49 (60), 28 (100). Anal calcd for C19H22N2S; C,
73.51, H, 7.14, N, 9.02. Found: C, 73.27; H, 7.34, N,
9.03.
tate=70/30); H NMR l 1.80 (d, J=7.1 Hz, 3H), 5.19
(q, J=7.1 Hz, 1H), 5.13 (d, J=16.1 Hz, 1H), 5.23 (d,
J=16.1 Hz, 1H), 6.95–7.55 (m, 13H), 7.85–8.11 (m,
1H); 13C NMR l 22.3, 47.5, 109.5, 118.6, 122.0, 122.3,
126.7, 127.1, 127.2, 127.6, 127.1, 127.2, 127.6, 127.7,
128.6, 128.7, 135.7, 142.1, 143.7, 150.9; IR (KBr) 3651,
2345, 1434, 1352, 738 cm−1; EIMS m/z (rel. intensity)
344 (M+, 50), 240 (100), 239 (25), 207 (32), 105 (75).
Anal calcd for C22H20N2S; C, 76.71, H, 5.85, N, 8.19.
Found: C, 76.03, H, 5.91, N, 8.15.
5.3. 2-[(1-Methylethyl)thio]-1-[(2,4,6-trimethylphenyl)-
methyl]benzimidazole, 3c
5.6. 1-[(3,5-Dimethylphenyl)methyl]-2-[(1-phenylethyl)-
thio]benzimidazole, 3f
The reaction was carried out as described above except
for using 1 (1.50 g, 7.78 mmol), potassium hydroxide
(558 mg, 11.7 mmol) and (2,4,6-trimethylphenyl)methyl
bromide (1.42 g, 8.58 mmol). The obtained crude
product was purified by column chromatography (silica
gel 30 g, hexane/ethyl acetate=90/10) to afford 3c (2.58
g, 93%): mp 104.2–106.0°C; Rf=0.51 (hexane/ethyl ace-
The reaction of 2 (2.00 g, 7.86 mmol), potassium
hydroxide (678 mg, 12.1 mmol) and (3,5-
dimethylphenyl)methyl bromide (1.72 g, 8.65 mmol)
followed by standard work-up gave the crude product
which was purified by column chromatography (silica
gel 70 g, hexane/ethyl acetate=90/10) to afford 3f (2.76
g, 93%): mp 71.0–72.0°C; Rf=0.63 (hexane/ethyl ace-
1
tate=80/20); H NMR l 1.51 (d, J=5.9 Hz, 6H), 2.20
1
(s, 6H), 2.30 (s, 3H), 4.21 (sep, J=5.9 Hz, 1H), 5.21 (s,
2H), 6.47–6.60 (m, 1H), 6.81–6.95 (m, 3H), 7.02–7.16
(m, 1H), 7.55–7.70 (m, 1H); 13C NMR l 20.2, 21.0,
23.5, 38.7, 44.2, 110.0, 118.2, 121.4, 121.6, 127.9, 130.0,
135.6, 137.6, 138.0, 143.9, 152.1; IR (KBr) 2959, 1422,
740 cm−1; EIMS m/z (rel. intensity) 324 (M+, 51), 249
(37), 191 (23), 133 (100). Anal calcd for C20H24N2S; C,
74.03, H, 7.46, N, 8.63. Found: C, 74.08, H, 7.61, N,
8.43.
tate=70/30); H NMR l 1.84 (d, J=7.0 Hz, 3H), 2.21
(s, 6H), 5.13 (s, 2H), 5.20 (q, J=7.0 Hz, 1H), 6.89 (s,
2H), 6.90 (s, 1H) 7.25–7.50 (m, 8H), 7.85–7.96 (m, 1H);
13C NMR l 21.5, 22.6, 47.7, 109.6, 118.2, 122.1, 124.2,
127.1, 127.5, 128.4, 129.3, 135.2, 138.2, 141.7, 150.6; IR
(KBr) 2920, 1424, 1368, 1189, 746, 700 cm−1; EIMS m/z
(rel. intensity) 372 (M+, 0.7), 267 (77), 234 (24), 118
(55), 104 (38). Anal calcd for C24H24N2S; C, 77.38, H,
6.49, N, 7.53. Found: C, 77.46, H, 6.55, N, 7.37.
5.4. 1-Methyl-2-[(1-methylethyl)thio]benzimidazole, 3d
5.7. 1-Methyl-2-[(1-phenylethyl)thio]benzimidazole, 3g
To a solution of 2-(1-methylthio)benzimidazole 1 (1.20
g, 6.24 mmol) in THF (30.9 mL) was added n-butyl-
lithium (1.72 mol L−1, solution in hexane, 3.99 mL, 6.86
mmol) at −10°C and the mixture was stirred for 15 min,
methyl iodide (0.582 mL, 9.36 mmol) was then added.
After stirring for 2 h, standard work-up described in
the preparation of 3a gave a solid which was purified by
column chromatography (silica gel 30 g, hexane/ethyl
acetate=90/10) to afford 3d (1.03 g, 80%): mp 30.0–
32.0°C; Rf=0.41 (hexane/ethyl acetate=90/10); 1H
NMR l 1.47 (d, J=6.9 Hz, 6H), 3.94 (sep, J=6.9 Hz,
1H), 4.18 (s, 3H), 7.34–7.51 (m, 3H), 7.81–7.83 (m, 1H);
13C NMR l 15.0, 23.3, 31.7, 55.1, 110.4, 121.7, 124.0,
125.8, 136.0, 141.0, 146.2; IR (neat) 2982, 1462, 1321,
1149, 1127, 813, 747, 704, 627 cm−1; EIMS m/z (rel.
intensity) 238 (M+, 15), 132 (100), 104 (10). Anal calcd
for C11H14N2S; C, 55.44, H, 5.95, N, 11.76. Found: C,
55.56, H, 6.01, N, 11.55.
The reaction was carried out as described in the prepa-
ration of 3d except for using 2 (111 mg, 0.437 mmol),
n-butyllithium (1.99 mol L−1, solution in hexane, 0.241
mL, 0.480 mmol), methyl iodide (0.030 mL, 0.480
mmol). Standard work-up as above gave a solid which
was purified by column chromatography (silica gel 1 g,
hexane/ethyl acetate=90/10) afford 3g (97.8 mg, 83%):
mp 73.1–75.4°C; Rf=0.46 (hexane/ethyl acetate=80/
1
20); H NMR l 1.85 (d, J=7.0 Hz, 3H), 3.54 (s, 3H),
5.13 (q, J=7.0 Hz, 1H), 7.10–7.50 (m, 8H), 7.65–7.72
(m, 1H); 13C NMR l 22.2, 30.0, 47.3, 108.8, 118.6,
121.9, 122.1, 127.2, 127.7, 128.6, 136.3, 142.1, 143.5,
150.6; IR (KBr) 3050, 1451, 1415, 1047, 740, 696 cm−1;
EIMS m/z (rel. intensity) 268 (M+, 29), 164 (100), 105
(58). Anal calcd for C16H16N2S; C, 71.60, H, 6.01, N,
10.44. Found: C, 71.58, H, 6.06, N, 10.42.
5.8. 2-[(1-Methylethyl)sulfonyl]-1-(phenylmethyl)-
benzimidazole, 4a
5.5. 2-[(1-Phenylethyl)thio]-1-(phenylmethyl)-
benzimidazole, 3e
To a solution of sulfide 3a (3.10 g, 11.0 mmol) in
CH2Cl2 (40.0 mL) was added m-CPBA (5.42 g, 22.0
mmol) at 0°C and the mixture was warmed to room
temperature over a period of 12 h. And then saturated
aqueous NaHCO3 was added and extracted with
CH2Cl2, dried over Na2SO4, and concentrated under
reduced pressure to leave a residue which was purified
by column chromatography (silica gel 60 g, hexane/
ethyl acetate=80/20) to afford 4a (3.08 g, 89%): mp
126.4–127.1°C; Rf=0.38 (hexane/ethyl acetate=80/20);
The reaction was carried out as described in the prepa-
ration of 3a except for using 2-[(1-phenylethyl)-
thio]benzimidazole 2 (2.54 g, 9.99 mmol), potassium
hydroxide (990 mg, 15.0 mmol) and benzyl chloride
(1.72 mL, 15.0 mol). Standard work-up gave a solid
which was purified by column chromatography (silica
gel 60 g, hexane/ethyl acetate=80/20) to afford 3e (3.08
g, 89%): mp 100.1–101.8°C; Rf=0.42 (hexane/ethyl ace-

3050
H. Sugimoto et al. / Tetrahedron: Asymmetry 14 (2003) 3043–3055
1H NMR l 1.41 (d, J=6.9 Hz, 6H), 3.79 (sep, J=6.9
Hz, 1H), 5.84 (s, 2H), 7.10–7.45 (m, 8H), 7.80–7.90 (m,
1H); 13C NMR l 14.9, 48.7, 55.1, 111.4, 121.8, 124.0,
126.0, 126.9, 127.1, 128.1, 128.8, 135.4, 135.6, 141.2,
146.2; IR (KBr) 3023, 2969, 1458, 1421, 1376, 1346,
1241, 741, 722 cm−1; EIMS m/z (rel. intensity) 314 (M+,
17), 207 (100), 159 (5), 91 (56). Anal calcd for
C17H18N2O2S; C, 64.94, H, 5.77, N, 8.91. Found: C,
65.14, H, 5.82, N, 8.91.
125.8, 136.0, 141.0, 146.2; IR (neat) 2982, 1462, 1321,
1149, 1127, 813, 747, 704, 627 cm−1; EIMS m/z (rel.
intensity) 238 (M+, 15), 132 (100), 104 (10). Anal calcd
for C11H14N2S; C, 55.44, H, 5.95, N, 11.76. Found: C,
55.56, H, 6.01, N, 11.55.
5.12. 2-[(1-Phenylmethyl)sulfonyl]-1-(phenylmethyl)benz-
imidazole, 4e
The reaction was carried out as described above except
for using 3e (2.86 g, 8.31 mmol) and m-CPBA (4.51 g,
18.2 mmol). Standard work-up gave the crude product,
which was purified by column chromatography (silica
gel 60 g, hexane/ethyl acetate=80/20) to afford 4e (2.94
g, 94%): mp 117.0–119.0°C; Rf=0.61 (hexane/ethyl ace-
5.9. 1-[(3,5-Dimethylphenyl)methyl]-2-[(1-methylethyl)-
sulfonyl]benzimidazole, 4b
The reaction was carried out as described above except
for using 3b (1.65 g, 5.31 mmol) and m-CPBA (2.62 g,
10.6 mmol). Standard work-up gave the crude product
which was purified by column chromatography (silica
gel 70 g, hexane/ethyl acetate=90/10) to afford 4b (1.63
g, 90%): mp 133.0–134.5°C; Rf=0.25 (hexane/ethyl ace-
1
tate=50/50); H NMR l 1.89 (d, J=7.2 Hz, 3H), 4.86
(q, J=7.2 Hz, 1H), 5.13 (d, J=14.9 Hz, 1H), 5.25 (d,
J=14.9 Hz, 1H), 6.95–7.50 (m, 13H), 7.85–8.11 (m,
1H); 13C NMR l 13.5, 48.2, 65.7, 111.5, 121.9, 124.1,
126.1, 126.8, 127.1, 127.9, 128.6, 128.7, 129.3, 129.8,
132.1, 135.3, 141.3, 145.9; IR (KBr) 3651, 2345, 1455,
1317, 1146, 1128, 722, 701 cm−1; EIMS m/z (rel. inten-
sity) 376 (M+, 30), 311 (46), 207 (63), 105 (100). Anal
calcd for C22H20N2O2S; C, 70.19, H, 5.35, N, 7.44.
Found: C, 70.14, H, 5.47, N, 7.37.
1
tate=90/10); H NMR l 1.42 (d, J=7.1 Hz, 6H), 2.24
(s, 6H), 3.76 (sep, J=7.1 Hz, 1H), 5.76 (s, 2H), 6.83 (s,
2H), 6.91 (s, 1H), 7.30–7.50 (m, 3H), 7.80–7.95 (m, 1H);
13C NMR l 15.1, 21.5, 48.9, 55.2, 111.4, 121.6, 123.9,
124.5, 125.8, 129.6, 135.1, 135.5, 138.2, 141.0, 145.9; IR
(KBr) 2965, 1458, 1321, 1121, 754 cm−1; EIMS m/z (rel.
intensity) 342 (M+, 25), 235 (100), 119 (31). Anal calcd
for C19H22N2O2S; C, 66.64, H, 6.48, N, 8.18. Found: C,
66.88, H, 6.49, N, 7.98.
5.13. 1-[(3,5-Dimethylphenyl)methyl]-2-[(1-phenylethyl)-
sulfonyl]benzimidazole, 4f
The reaction was carried out as described above except
for using 3f (2.22 g, 5.96 mmol) and m-CPBA (2.93 g,
11.9 mmol). Standard work-up gave the crude product,
which was purified by column chromatography (silica
gel 60 g, hexane/ethyl acetate=80/20) to afford 4f (1.83
g, 76%): mp 135.0–136.0°C; Rf=0.63 (hexane/ethyl ace-
5.10. 2-[(1-Methylethyl)sulfonyl]-1-[(2,4,6-trimethyl-
phenyl)methyl]benzimidazole, 4c
The reaction was carried out as described above except
for using 3c (2.28 g, 7.03 mmol) and m-CPBA (3.47 g,
14.1 mmol). Standard work-up gave the crude product
which was purified by column chromatography (silica
gel 100 g, hexane/ethyl acetate=90/10) to afford 4c
(1.69 g, 68%): mp 133.5–136.0°C; Rf=0.59 (hexane/
1
tate=70/30); H NMR l 1.87 (d, J=7.2 Hz, 3H), 2.20
(s, 6H), 4.77 (q, J=7.2 Hz, 1H), 4.95 (d, J=16.2 Hz,
1H), 5.14 (d, J=16.2 Hz, 1H), 6.65 (s, 2H), 6.84 (s, 1H),
7.13–7.25 (m, 8H), 7.90–8.10 (m, 1H); 13C NMR l 13.6,
21.3, 48.1, 65.7, 111.4, 121.5, 123.8, 124.2, 125.8, 128.3,
129.0, 129.4, 131.7, 134.9, 135.1, 138.0, 140.9, 145.4; IR
(KBr) 2919, 1322, 1146, 1129, 759 cm−1; EIMS m/z (rel.
intensity) 404 (M+, 40), 340 (42), 236 (65), 106 (59), 27
(100). Anal calcd for C24H24N2O2S; C, 71.26, H, 5.93,
N, 6.93. Found: C, 71.42, H, 5.98, N, 6.71.
1
ethyl acetate=70/30); H NMR l 1.55 (d, J=6.9 Hz,
6H), 2.22 (s, 6H), 2.31 (s, 3H), 4.18 (sep, J=6.9 Hz,
1H), 5.90 (s, 2H), 6.45–6.55 (m, 1H), 6.90 (s, 2H),
7.00–7.18 (m, 1H), 7.20–7.32 (m, 1H), 7.70–7.85 (m,
1H); 13C NMR l 15.2, 20.0, 21.0, 45.6, 54.6, 112.4,
121.4, 123.4, 126.0, 127.3, 130.0, 135.2, 137.9, 138.5,
141.2, 147.0; IR (KBr) 3650, 2978, 1445, 1312, 1132,
1054, 755, 695 cm−1; EIMS m/z (rel. intensity) 356 (M+,
17), 249 (23), 133 (100). Anal calcd for C20H24N2O2S; C,
67.38, H, 6.79, N, 7.86. Found: C, 67.45, H, 6.89, N,
7.68.
5.14. 1-Methyl-2-[(1-phenylethyl)sulfonyl]benzimidazole,
4g
The reaction was carried out as described above except
for using 3g (1.32 g, 4.91 mmol) and m-CPBA (2.42 g,
9.82 mmol). Standard work-up gave the crude product,
which was purified by column chromatography (silica
gel 80 g, hexane/ethyl acetate=70/30) to afford 3g (1.45
g, 98%): mp 139.0–140.5°C; Rf=0.46 (hexane/ethyl ace-
5.11. 1-Methyl-2-[(1-methylethyl)sulfonyl]benzimidazole,
4d
1
The reaction was carried out as described above except
for using 3d (812 mg, 3.94 mmol) and m-CPBA (1.94 g,
7.87 mmol). Standard work-up gave the crude product,
which was purified by column chromatography (silica
gel 20 g, hexane/ethyl acetate=90/10) to afford 4d (902
tate=80/20); H NMR l 1.94 (d, J=7.2 Hz, 3H), 3.38
(s, 3H), 4.80 (q, J=7.2 Hz, 1H), 7.10–7.54 (m, 8H),
7.85–8.00 (m, 1H); 13C NMR l 13.0, 30.7, 66.1, 110.5,
121.9, 124.0, 125.9, 128.5, 129.3, 129.6, 132.2, 135.7,
141.1, 145.5; IR (KBr) 2365, 2345, 1459, 1324, 1156,
1132, 815, 747 cm−1; EIMS m/z (rel. intensity) 300 (M+,
10), 235 (58), 132 (26), 105 (100). Anal calcd for
C16H16N2 O2S; C, 63.94, H, 5.37, N, 9.33. Found: C,
63.94, H, 5.42, N, 9.32.
1
mg, 96%): Rf=0.64 (hexane/ethyl acetate=80/20); H
NMR l 1.47 (d, J=6.9 Hz, 6H), 3.94 (sep, J=6.9 Hz,
1H), 4.18 (s, 3H), 7.34–7.51 (m, 3H), 7.81–7.83 (m, 1H);
13C NMR l 15.0, 23.3, 31.7, 55.1, 110.4, 121.7, 124.0,

H. Sugimoto et al. / Tetrahedron: Asymmetry 14 (2003) 3043–3055
3051
5.15. 2-{[1-Methyl-2-(phenylseleno)ethyl]sulfonyl}-1-
(phenylmethyl)benzimidazole, 5a
5.18. 1-Methyl-2-{[1-phenyl-1-(phenylseleno)ethyl]-
sulfonyl}benzimidazole, 5g
To a solution of 1,1,1,3,3,3-hexamethyldisilazane (1.47
mL, 6.69 mmol) in THF (4.0 mL) was added n-butyl-
lithium (1.99 mol L−1 in hexane, 3.50 mL, 6.69 mmol)
at 0°C, and the mixture was stirred for 30 min. After
cooling the mixture at −78°C, a solution of sulfone 4a
(1.10 g, 3.48 mmol) in THF (10 mL) and a solution of
hexamethyphosphoramide (0.219, 6.69 mmol) in THF
(3.0 mL) were added. After stirring for 30 min, a
solution of phenylselenyl bromide (1.23 g, 5.22 mmol)
in THF (0.5 mL) was then added. The reaction mixture
was warmed up and water (10 mL) was then added.
The combined organic solution was extracted with
CH2Cl2, dried over Na2SO4, and concentrated under
reduced pressure to leave a residue which was purified
by column chromatography (silica gel 80 g, benzene/
ethyl acetate=97/3) to afford 5a (924 mg, 56%): mp
142.7–144.5°C; Rf=0.49 (hexane/ethyl acetate=60/40);
1H NMR l 1.77 (s, 6H), 5.91 (s, 2H), 7.14–7.50 (m,
11H), 7.55–7.70 (m, 2H), 7.80–7.92 (m, 1H); 13C NMR
l 24.8, 49.4, 69.0, 111.6, 122.0, 124.1, 125.9, 126.1,
127.0, 128.0, 128.8, 129.7, 135.6, 135.7, 138.3, 141.5,
144.7; IR (KBr) 3056, 1605, 1453, 1323, 1145, 1131,
741, 722 cm−1; EIMS m/z (rel. intensity) 470 (M+, 0.3),
365 (4), 208 (44), 91 (100). Anal calcd for
C23H22N2O2SSe; C, 58.84, H, 4.72, N, 5.97. Found: C,
58.88, H, 4.83, N, 5.82.
The reaction was carried out as described above except
for using sulfone 4g (1.45 g, 4.83 mmol) to afford 5g
(1.13 g, 51%): mp 162.0–165.0°C; Rf=0.43 (benzene/
1
ethyl acetate=95/5); H NMR l 2.10 (s, 3H), 3.13 (s,
3H), 7.15–7.25 (m, 13H), 7.75–7.90 (m, 1H); 13C NMR
l 22.4, 30.7, 73.1, 110.3, 121.6, 123.7, 125.6, 126.0,
128.1, 128.6, 129.1, 129.8, 135.0, 135.5, 138.8, 140.7,
143.3; IR (KBr) 1467, 1326, 1156, 1133, 810, 750, 696
cm−1; SIMS (rel. intensity) 456 (M+, 66), 307 (100), 300
(27). Anal calcd for C22H20N2O2SSe; C, 58.02, H, 4.43,
N, 6.15. Found: C, 58.00, H, 4.42, N, 6.15.
5.19. 2-[(1-Methylethenyl)sulfonyl]-1-(phenylmethyl)-
benzimidazole, 6a
To a solution of sulfide 5a (808 mg, 1.72 mmol) in
CH2Cl2 (3.0 mL) was added m-CPBA (594 mg, 2.41
mmol) at 0°C and the mixture was warmed to room
temperature over a period of 2 h. Then saturated
aqueous NaHCO3 was added and extracted with
CH2Cl2, dried over Na2SO4, and concentrated under
reduced pressure to leave a residue which was purified
by column chromatography (silica gel 60 g, hexane/
ethyl acetate=80/20) to afford 6a (1.69 g, 68%): mp
126.9–128.2°C; Rf=0.30 (hexane/ethyl acetate=70/30);
1H NMR l 2.18 (s, 3H), 5.82 (s, 2H), 5.85 (s, 1H), 6.30
(s, 1H), 7.12–7.49 (m, 8H), 7.84–7.98 (m, 1H); 13C
NMR l 16.8, 48.8, 111.4, 122.0, 124.1, 126.1, 126.8,
127.2, 127.4, 128.1, 128.8, 135.2, 135.9, 141.3, 144.9,
146.7; IR (KBr) 3651, 2349, 1460, 1324, 1121, 817, 730,
698 cm−1; EIMS m/z (rel. intensity) 312 (M+, 31), 247
(43), 207, (48), 91 (100). Anal calcd for C17H16N2O2S;
C, 65.36, H, 5.16, N, 8.97. Found: C, 65.36, H, 5.19, N,
8.94.
5.16. 1-Methyl-2-{[1-methyl-1-(phenylseleno)ethyl]-
sulfonyl}benzimidazole, 5d
The reaction was carried out as described above except
for using 4d (150 mg, 0.269 mmol) to afford 5d (148
mg, 60%): mp 127–128°C; Rf=0.27 (hexane/ethyl ace-
tate=80/20); 1H NMR l 1.81 (s, 6H), 4.22 (s, 3H),
7.15–7.68 (m, 8H), 7.82–7.91 (m, 1H); 13C NMR l 24.7,
32.4, 68.5, 110.6, 121.9, 124.0, 125.7, 125.9, 128.8,
129.7, 136.1, 138.2, 141.3, 144.5; IR (KBr) 1456, 1322,
1146, 1131, 1095, 811, 762, 694 cm−1; EIMS m/z (rel.
intensity) 394 (M+, 6), 199 (100) 197 (71), 157 (31), 132
(57), 131 (36), 119 (38). Anal calcd for C17H18N2O2SSe;
C, 51.91, H, 4.61, N, 7.12. Found: C, 51.88, H, 4.61, N,
7.16.
5.20. 1-[(3,5-Dimethylphenyl)methyl]-2-[(1-methyl-
ethenyl)sulfonyl]benzimidazole, 6b
To a solution of diisopropylamine (0.245 mL, 1.77
mmol) in THF (1.2 mL) was added n-butyllithium (1.48
mol L−1 in hexane, 1.19 mL, 1.77 mmol) at 0°C, and
the mixture was stirred for 30 min. After cooling at
−78°C, a solution of sulfone 4b (302 mg, 0.882 mmol)
in THF (3.0 mL) and a solution of hexamethyphospho-
ramide (0.307 mL, 1.77 mmol) in THF (2.0 mL) were
added. The mixture was stirred for 30 min, and a
solution of diphenyl diselenide (551 mg, 1.77 mmol) in
THF (2.0 mL) was then added. The reaction mixture
was warmed to room temperature, and water (5.0 mL)
was then added. The mixture was extracted with
CH2Cl2. The combined organic solution was dried over
Na2SO4, and concentrated under reduced pressure to
leave a residue from which excess diphenyl diselenide
was removed by column chromatography (silica gel 10
g, hexane/ethyl acetate=95/5). The obtained solution
was concentrated under reduced pressure. The residue
was dissolved in CH2CH2 (5.0 mL). Then, m-CPBA
(218 mg, 0.883 mmol) was added at 0°C, the mixture
was warmed to room temperature over a period of 2 h.
Saturated aqueous NaHCO3 was added and extracted
5.17. 2-{[1-Phenyl-1-(phenylseleno)ethyl]sulfonyl}-1-
(phenylmethyl)benzimidazole, 5e
The reaction was carried out as described above except
for using sulfone 4e (1.04 g, 2.77 mmol) to afford 5e
(1.19 g, 81%): mp 138.8–140.4°C; Rf=0.20 (benzene);
1H NMR l 2.17 (s, 3H), 4.30 (d, J=15.8 Hz, 1H), 5.00
(d, J=15.8 Hz, 1H), 6.90–7.55 (m, 17H), 7.70–8.11 (m,
2H); 13C NMR l 22.4, 47.8, 73.6, 111.6, 121.9, 123.9,
126.0, 126.3, 126.8, 127.1, 127.8, 128.4, 128.6, 128.7,
128.9, 129.5, 130.1, 135.2, 135.3, 139.1, 141.4, 144.0; IR
(KBr) 3070, 1327, 1146, 744, 723, 693 cm−1; SIMS (rel.
intensity) 532 (M+, 4.6), 272 (74), 240 (5.2), 208 (100).
Anal calcd for C28H24N2O2SSe; C, 63.27, H, 4.55, N,
5.27. Found: C, 63.23, H, 4.64, N, 5.22.

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H. Sugimoto et al. / Tetrahedron: Asymmetry 14 (2003) 3043–3055
with CH2Cl2, dried over Na2SO4, and concentrated
under reduced pressure to leave a residue which was
purified by column chromatography (silica gel 30 g,
hexane/ethyl acetate=90/10) to afford 6b (85.9 mg, two
steps 29%): mp 138.9–141.7°C; Rf=0.33 (hexane/ethyl
5.24. 1-[(3,5-Dimethylphenyl)methyl]-2-[(1-phenyl-
ethenyl)sulfonyl]benzimidazole, 6f
The reaction starting from sulfone 4f (1.44 g, 3.87
mmol) afforded 6f (147mg, two steps 24%): mp 117.8–
120.3°C; Rf=0.43 (hexane/ethyl acetate=70/30); 1H
NMR l 2.20 (s, 6H), 5.45 (s, 2H), 6.10 (s, 1H), 6.62 (s,
2H), 6.72 (s, 1H), 6.86 (s, 1H), 7.00–7.85 (m, 8H),
7.90–8.10 (m, 1H); 13C NMR l 21.4, 48.7, 111.5, 121.8,
123.8, 124.2, 125.9, 128.2, 128.4, 129.0, 129.4, 131.0,
134.7, 135.6, 138.1, 141.0, 146.4, 148.7; IR (KBr) 2919,
1327, 1148, 960, 821, 758 cm−1; EIMS m/z (rel. inten-
sity) 402 (M+, 5.9), 337 (13), 118 (52), 27 (100). Anal
calcd for C24H22N2O2S; C, 71.61, H, 5.51, N, 6.96.
Found: C, 71.88, H, 5.52, N, 6.67.
1
acetate=80/20); H NMR l 2.18 (s, 3H), 2.24 (s, 6H),
5.72 (s, 2H), 5.86 (s, 1H), 6.31 (s, 1H), 6.76 (s, 2H), 6.89
(s, 1H), 7.10–7.20 (m, 3H), 7.85–8.10 (m, 1H); 13C
NMR l 16.9, 21.4, 48.8, 111.4, 121.6, 123.8, 124.2,
125.8, 127.0, 129.4, 134.8, 135.6, 138.1, 140.9, 144.6,
146.2; EIMS m/z (rel. intensity) 340 (M+, 11), 275 (69),
236 (55), 118 (100). Anal calcd for C19H20N2O2S; C,
67.03, H, 5.92, N, 8.23. Found: C, 67.09; H, 5.94, N,
8.14.
5.21. 2-[(1-Methylethenyl)sulfonyl]-1-[(2,4,6-trimethyl-
phenyl)methyl]benzimidazole, 6c
5.25. 1-Methyl-2-[(1-phenylethenyl)sulfonyl]-
benzimidazole, 6g
The reaction as described above starting from 4c (1.20
g, 3.37 mmol) afforded 6c (654 mg, 2 steps 38%): mp
153.0–157.2°C; Rf=0.38 (hexane/ethyl acetate=80/20);
1H NMR l 2.21 (s, 6H), 2.33 (s, 6H), 5.85 (s, 2H), 6.08
(s, 1H), 6.50–6.67 (m, 1H), 6.50 (s, 1H), 6.91 (s, 2H)
7.00–7.18 (m, 1H), 7.20–7.35 (m, 1H), 7.75–7.90 (m,
1H); 13C NMR l 17.3, 19.9, 21.0, 45.7, 112.4, 121.7,
123.4, 125.7, 127.1, 127.8, 129.7, 135.5, 137.9, 138.6,
141.3, 145.0, 147.3; IR (KBr) 3650, 1459, 1315, 1121,
741 cm−1; EIMS m/z (rel. intensity) 354 (M+, 12), 248
(81), 247 (57), 133 (100), 117 (41), 91 (43). Anal calcd
for C20H22N2O2S; C, 67.77, H, 6.26, N, 7.90. Found: C,
67.70, H, 6.37, N, 7.86
The reaction starting from sulfone 5g (803 mg, 1.76
mmol) afforded 6g (457 mg, 87%): mp 83.5–86.5°C;
Rf=0.37 (hexane/ethyl acetate=70/30); 1H NMR l
3.75 (s, 3H), 6.20 (s, 1H), 6.85 (s, 1H), 7.10–7.60 (m,
8H), 7.80–7.95 (m, 1H); 13C NMR l 31.5, 110.3, 121.7,
123.8, 125.7, 128.2, 128.3, 129.2, 129.5, 131.0, 135.8,
140.8, 146.3, 148.9; IR (KBr) 1457, 1330, 1156, 729, 749
cm−1; EIMS m/z (rel. intensity) 298 (M+, 99), 233 (77),
132 (48), 103 (100). Anal calcd for C16H14N2O2S; C,
64.41, H, 4.73, N, 9.39. Found: C, 64.50, H, 4.79, N,
9.24.
General procedure for the chiral Lewis acid-mediated
intermolecular radical reaction of vinyl sulfones 6a–g
5.22. 1-Methyl-2-[(1-methylethenyl)sulfonyl]-
benzimidazole, 6d
A 0.01 mol/L CH2Cl2 solution of 1.1 equiv. of Lewis
acid and 1.2 equiv. of bis(oxazoline) was stirred at
room temperature for 1 h, and then to this mixture was
added vinylsulfones 6a–g. After stirred for 1 h, the
mixture was cooled to −78°C and alkyl iodide (2
equiv.), tributyltin hydride (2 equiv.) and triethylborane
(2 equiv.) were added. The reaction mixture was stirred
at −78°C for 1 h. When the reaction was not completed,
another 2 equiv. of tributyltin hydride and triethylbo-
rane were added, and the reaction was continued for an
additional 1 h. Then 8% KF solution was added, and
stirred for 1 h at room temperature. The aqueous layer
was extracted with CH2Cl2, and the combined organic
extracts were dried over Na2SO4, and concentrated
under reduced pressure to leave a residue which was
purified by flash column chromatography to afford
7a–g.
The reaction as described above staring from 5d (141
mg, 0.358 mmol) afforded 6d (46.5 mg, 55%): mp
94.8–95.7°C; Rf=0.21 (hexane/ethyl acetate=70/30);
1H NMR l 2.24 (s, 3H), 4.12 (s, 3H), 6.02 (s, 1H), 6.47
(s, 1H), 7.21–7.65 (m, 3H), 7.82–7.98 (m, 1H); 13C
NMR l 16.7, 31.5, 110.4, 121.8, 123.9, 125.8, 127.2,
136.2, 141.0, 145.0, 146.5; IR (KBr) 1451, 1323, 1151,
1126, 1105, 818, 742, 695 cm−1; EIMS m/z (rel. inten-
sity) 236 (M+, 48), 132 (100), 131 (56). Anal calcd for;
C11H12N2O2S; C, 55.91, H, 5.12, N, 11.86. Found: C,
55.88, H, 5.14, N, 11.87.
5.23. 2-[(1-Phenylethenyl)sulfonyl]-1-(phenylmethyl)-
benzimidazole, 6e
The reaction as described above using 5e (398 mg, 0.713
mmol) afforded 6e (179 mg, 63%): mp 163.8–165.2°C;
Rf=0.40 (benzene/ethyl acetate=90/10); 1H NMR l
5.57 (s, 2H), 6.14 (s, 1H), 6.77 (s, 1H), 6.95–7.10 (m,
2H), 7.20–7.43 (m, 11H), 7.81–8.05 (m, 1H); 13C NMR
l 48.6, 111.5, 122.0, 124.0, 126.1, 126.7, 127.9, 128.4,
128.7, 129.4, 129.6, 131.3, 135.1, 135.7, 141.4, 146.7,
149.1; IR (KBr) 3651, 2349, 1460, 1329, 1146, 826, 745,
733, 695 cm−1; EIMS m/z (rel. intensity) 374 (M+, 87),
309 (25) 207 (40), 91 (100). Anal calcd for
C22H18N2O2S; C, 70.57, H, 4.85, N, 7.48. Found: C,
70.57, H, 4.93, N, 7.48.
5.26. (S)-1-(Phenylmethyl)-2-[(1,3,3-trimethylbutyl)-
sulfonyl]benzimidazole, 7a
[h]2D0 −5.32 (c 0.224, CHCl3, 56% ee); mp 125.2–
127.0°C; Rf=0.30 (hexane/ethyl acetate=70/30); 1H
NMR l 0.85 (s, 9H), 1.34 (dd, J=8.1 Hz, J=14.5 Hz,
1H), 1.43 (d, J=6.9 Hz, 3H), 2.12 (dd, J=1.7 Hz,
J=14.5 Hz, 1H), 3.40–3.60 (m, 1H), 5.80 (d, J=16.0
Hz, 1H), 5.92 (d, J=16.0 Hz, 1H), 7.10–7.45 (m, 8H),
7.82–8.05 (m, 1H); 13C NMR l 16.2, 29.4, 30.9, 41.4,
48.6, 57.3, 111.3, 121.9, 124.1, 126.0, 126.9, 128.1,

H. Sugimoto et al. / Tetrahedron: Asymmetry 14 (2003) 3043–3055
3053
1
128.9, 135.6, 135.8, 141.3, 146.1; IR (KBr) 2948, 1310,
1128, 756, 638 cm−1; EIMS m/z (rel. intensity) 370 (M+,
6), 313 (40), 207 (100), 91 (98), 57 (59). Anal calcd for
C21H26N2O2S; C, 68.08, H, 7.07, N, 7.56. Found: C,
68.10, H, 7.22, N, 7.40; HPLC (Chiralcel OD-H, hex-
ane/i-PrOH 8=97:3, flow rate 0.5 mL min−1) tR 40.6
(S), 47.3 (R) min.
30); H NMR l 0.87 (t, J=7.1 Hz, 3H), 1.10–1.75 (m,
6H), 1.80–2.20 (m, 1H), 3.40–3.70 (m, 1H), 5.84 (s, 2H),
7.17–7.50 (m, 8H), 7.82–8.00 (m, 1H); 13C NMR l 12.4,
13.6, 19.5, 30.1, 48.6, 59.3, 111.3, 121.8, 124.0, 126.0,
126.9, 128.1, 128.8, 135.5, 135.9, 141.2, 146.3; IR (KBr)
2964, 1332, 1298, 1128, 725 cm−1; EIMS m/z (rel.
intensity) 342 (M+, 0.9), 207 (100), 91 (90). Anal calcd
for C19H22N2O2S; C, 66.64, H, 6.48, N, 8.18. Found: C,
66.50, H, 6.55, N, 8.26. HPLC (Chiralcel OD-H, hex-
ane/i-PrOH=97:3, flow rate 0.5 mL min−1) tR 41.1,
46.1 min.
5.27. (S)-1-[(3,5-Dimethylphenyl)methyl]-2-[(1,3,3-
trimethylbutyl)sulfonyl]benzimidazole, 7b
[h]2D0 −8.29 (c 0.338, CHCl3, 82% ee) mp 91.9–94.2°C;
Rf=0.20 (hexane/ethyl acetate=90/10); 1H NMR l
0.81 (s, 9H), 1.10–1.25 (m, 4H), 2.00–2.20 (m, 7H),
3.15–3.32 (m, 1H), 5.70 (d, J=16.0 Hz, 1H), 5.83 (d,
J=16.0 Hz, 1H), 6.80 (s, 2H), 6.90 (s, 1H), 7.10–7.28
(m, 3H), 7.80–8.15 (m, 1H); 13C NMR l 16.3, 21.4,
29.4, 30.9, 41.4, 48.6, 57.2, 111.2, 121.6, 123.8, 124.3,
125.8, 129.5, 135.2, 138.2, 140.9, 145.6; IR (KBr) 3651,
2960, 1370, 1146, 722 cm−1; EIMS m/z (rel. intensity)
398 (M+, 9.4), 236 (100), 118 (35). Anal calcd for
C23H30N2O2S; C, 69.31, H, 7.59, N, 7.03. Found: C,
69.22, H, 7.87, N, 6.90. HPLC (Chiralcel OD-H, hex-
ane/i-PrOH=97:3, flow rate 0.5 mL min−1) tR 30.5 (S),
33.3 (R) min.
5.31. 2-[(1,3-Dimethylbutyl)sulfonyl]-1-(phenylmethyl)-
benzimidazole, 15
Mp 103.6–105.2°C; Rf=0.38 (hexane/ethyl acetate=80/
20); 1H NMR l 0.78 (d, J=6.1 Hz, 3H), 0.91 (d, J=6.1
Hz, 3H), 1.33 (d, J=6.8 Hz, 3H), 1.40–1.85 (m, 3H),
3.50–3.72 (m, 1H), 5.84 (s, 2H), 7.14–7.50 (m, 8H),
7.81–8.00 (m, 1H); 13C NMR l 12.7, 20.7, 23.4, 25.0,
36.5, 48.6, 58.1, 111.3, 121.8, 124.0, 126.0, 126.8, 128.1,
128.8, 135.5, 136.6, 135.7, 141.2, 146.2; IR (KBr) 2956,
1305, 1126, 755, 637 cm−1; MS (CI) m/e 357 ([M+H]+,
100), 250 (8), 209 (16). Anal calcd for C20H24N2O2S; C,
67.38, H, 6.79, N, 7.86. Found: C, 67.37, H, 6.95, N,
7.71. HPLC (Chiralpac AD-H, hexane/i-PrOH=97:3,
flow rate 1.0 mL min−1) tR 33.1, 42.1 min.
5.28. 2-[(1,3,3-Trimethylbutyl)sulfonyl]-1-[2,4,6-
(trimethylphenyl)methyl]benzimidazole, 7c
Mp 105.4–108.1°C; Rf=0.33 (hexane/ethyl acetate=90/
10); 1H NMR l 0.99 (s, 9H), 1.49 (dd, J=8.0 Hz,
J=14.0 Hz, 1H), 1.60 (d, J=8.0 Hz, 3H), 2.10–2.40 (m,
10H), 3.87–4.10 (m, 1H), 5.91 (s, 2H), 6.41–6.55 (m,
1H), 6.90 (s, 2H), 7.00–7.15 (m, 1H), 7.16–7.32 (m, 1H),
7.82–7.90 (m, 1H); 13C NMR l 16.9, 20.3, 21.3, 29.9,
31.4, 41.7, 45.9, 57.2, 112.7, 121.8, 123.7, 125.8, 127.6,
130.0, 135.5, 138.1, 138.8, 141.5, 147.2; IR (KBr) 2959,
1318, 1141, 744 cm−1; MS (CI) m/e 413 ([M+H]+, 100),
251 (31), 133 (68). Anal calcd for C24H32N2O2S; C,
69.87, H, 7.82, N, 6.79. Found: C, 69.81, H, 7.97, N,
6.70. HPLC (Chiralcel OD-H, hexane/i-PrOH=97:3,
flow rate 0.2 mL min−1) tR 29.2, 31.5 min.
5.32. 2-[(2-Cyclohexyl-1-methylethyl)sulfonyl]-1-(phenyl-
methyl)benzimidazole, 16
Mp 77.0–79.5°C; Rf=0.34 (hexane/ethyl acetate=80/
1
20); H NMR l.60–2.25 (m, 16H), 3.50–3.70 (m, 1H),
5.84 (d, J=18.1 Hz, 2H), 7.10–7.45 (m, 8H), 7.81–8.00
(m, 1H); 13C NMR l 12.8, 25.6, 25.9, 26.1, 31.4, 33.8,
34.2, 35.0, 48.5, 57.3, 111.2, 121.7, 123.9, 125.9, 126.7,
127.9, 128.7, 135.5, 135.6, 141.1, 146.1; IR (KBr) 2921,
1459, 1313, 1127, 751, 726 cm−1 SIMS (rel. intensity)
396 (M+, 100), 272 (29), 208 (28), 206 (36). Anal calcd
for; C23H28N2O2S; C, 69.66, H, 7.12, N, 7.06. Found:
C, 69.61, H, 7.28, N, 6.94; HPLC (Chiralcel OD-H,
hexane/i-PrOH=97:3, flow rate 0.5 mL min−1) tR 38.8,
42.5 min.
5.29. 1-Methyl-2-[(1,3,3-trimethylbutyl)sulfonyl]-
benzimidazole, 7d
Mp 94.9–97.2°C; Rf=0.39 (hexane/ethyl acetate=80/
20); 1H NMR l 0.93 (s, 9H), 1.41 (dd, J=8.0 Hz,
J=14.5 Hz, 1H), 1.43 (d, J=4.4 Hz, 3H), 2.19 (dd,
J=2.0 Hz, J=14.5 Hz, 1H), 3.60–3.80 (m, 1H), 4.17 (s,
3H), 7.30–7.55 (m, 3H), 7.82–7.96 (m, 1H); 13C NMR l
16.3, 29.5, 31.0, 31.7, 41.7, 57.3 110.4, 121.7, 123.9,
125.7, 136.0, 141.1, 146.2; IR (KBr) 2960, 1317, 1152,
745 cm−1; EIMS m/z (rel. intensity) 294 (M+, 0.8), 132
(100), 57 (38). Anal calcd for; C15H22N2O2S; C, 61.19,
H, 7.53, N, 9.52. Found: C, 61.31, H, 7.69, N, 9.23.
HPLC (Chiralcel OD-H, hexane/i-PrOH=97:3, flow
rate 0.5 mL min−1) tR 41.1, 46.1 min.
5.33. 2-[(1-Phenylbutyl)sulfonyl]-1-(phenylmethyl)-
benzimidazole, 7e
Mp 85.1–87.6°C; Rf=0.28 (hexane/ethyl acetate=80/
1
20); H NMR l 0.88 (t, J=7.3 Hz, 3H), 1.10–1.50 (m,
2H), 2.10–2.70 (m, 2H), 4.68 (dd, J=4.0, 11.4 Hz, 1H),
5.08 (d, J=15.3 Hz, 1H), 5.25 (d, J=15.3 Hz, 1H),
6.80–7.50 (m, 13H), 7.80–8.10 (m, 1H); 13C NMR l
13.7, 20.0, 28.8, 48.2, 70.8, 111.3, 121.7, 123.9, 125.8,
126.6, 127.7, 128.4, 128.5, 129.0, 130.0, 130.5, 135.0,
135.1, 141.1, 145.8; IR (KBr) 2961, 1320, 1146, 752
cm−1 EIMS m/z (rel. intensity) 404 (M+, 23), 208 (39),
150 (36), 92 (79), 28 (100). Anal calcd for C24H24N2O2S,
C, 71.26, H, 5.98, N, 6.93. Found: C, 71.39, H, 5.98, N,
6.79.
5.30. 2-[(1-Methylbutyl)sulfonyl]-1-(phenylmethyl)-
benzimidazole, 14
Mp 83.9–85.7°C; Rf=0.64 (hexane/ethyl acetate=70/

3054
H. Sugimoto et al. / Tetrahedron: Asymmetry 14 (2003) 3043–3055
5.34. (R)-1-[(3,5-Dimethylphenyl)methyl]-2-[(1-phenyl-
added. After stirring for 5 min saturated aqueous
NaHCO3 was added. The mixture was extracted with
CH2Cl2, dried over Na2SO4, and concentrated under
reduced pressure to leave a residue which was purified
by column chromatography (silica gel 15 g, hexane/
ethyl acetate=95/5) to afford 18 (48.8 mg, 14%): [h]D20
−35.3 (c 0.928, CHCl3); mp 66.5–68.0°C; Rf=0.37 (hex-
butyl)sulfonyl]benzimidazole, 7f
[h]2D0 +52.7 (c 0.228, CHCl3, 68% ee); mp 34.2–36.5°C;
Rf=0.43 (hexane/ethyl acetate=70/30); 1H NMR l
0.86 (t, J=7.4 Hz, 3H), 1.05–1.59 (m, 2H), 2.0–2.7 (m,
8H), 4.55 (dd, J=4.2 Hz, J=11.2 Hz, 1H), 4.90 (d,
J=16.0 Hz, 1H), 5.19 (d, J=16.0 Hz, 1H), 6.65 (s, 2H),
7.19 (s, 1H), 7.00–7.65 (m, 8H), 7.85–8.28 (m, 1H); 13C
NMR l 13.8, 20.0, 21.4, 28.9, 48.2, 70.9, 111.4, 121.0,
124.0, 124.4, 125.9, 128.4, 129.0, 129.4, 130.0, 130.4,
135.0, 135.1, 138.1, 140.8, 145.7; IR (KBr) 2961, 2873,
1329, 1145, 1129, 747, 699 cm−1; EIMS m/z (rel. inten-
sity) 432 (M+, 32), 367 (32), 235 (69), 119 (39), 91 (100).
Anal calcd for C26H28N2O2S; C, 72.19, H, 6.52, N, 6.48.
Found: C, 72.30, H, 6.65, N, 6.23. HPLC (Chiralpac
AD-H, hexane/i-PrOH=95:5, flow rate 1.0 mL min−1)
tR 41.8 (R), 57.8 (S) min.
1
ane/ethyl acetate=90/10); H NMR l 0.98 (s, 9H), 1.51
(d, J=6.6 Hz, 3H), 1.54 (dd, J=5.5, 14.6 Hz, 1H), 1.70
(dd, J=6.1, 14.6 Hz, 1H), 3.90–4.10 (m, 1H), 5.34 (s,
2H), 7.06–7.35 (m, 8H), 7.61–7.80 (m, 1H); 13C NMR l
24.9, 29.9, 31.4, 40.4, 47.5, 50.5, 109.2, 118.5, 121.9,
122.0, 126.8, 127.7, 128.7, 135.8, 135.9, 143.8, 151.8; IR
(KBr) 2964, 1421, 1374, 742 cm−1; EIMS m/z (rel.
intensity) 338 (M+, 9), 240 (77) 207 (23), 91 (100), 57
(31). Anal calcd for C21H26N2S; C, 74.51, H, 7.74, N,
8.28. Found: C, 74.54, H, 7.95, N, 8.05; HPLC (Chiral-
cel OD-H, hexane/i-PrOH=97:3, flow rate 0.3 mL
min−1) tR 25.1 (S), 27.0 (R) min.
5.35. (R)-1-Methyl-2-[(1-phenylbutyl)sulfonyl]-
benzimidazole, 7g
5.38. (R)-1-(Phenylmethyl)-2-[(1,3,3-trimethyl-
butyl)sulfonyl]benzimidazole, (R)-7a
[h]2D0 +82.5 (c 0.220, CHCl3, 91% ee); Rf=0.43 (hexane/
ethyl acetate=70/30); H NMR l 0.92 (t, J=7.4 Hz,
1
To a solution of sulfide 18 (25.3 mg, 0.0747 mmol) in
CH2Cl2 (4.0 mL) was added m-CPBA (36.9 mg, 0.149
mmol) at 0°C and the mixture was gradually warmed to
room temperature over a period of 2 h. Saturated
aqueous NaHCO3 was added and extracted with
CH2Cl2, dried over Na2SO4, and concentrated under
reduced pressure to leave a residue which was purified
by column chromatography (silica gel 10 g, hexane/
ethyl acetate=90/10) to afforded (R)-7a (27.6 mg,
99%): [h]2D0 +7.22 (c 0.460, CHCl3); HPLC (Chiralcel
OD-H, hexane/i-PrOH=97:3, flow rate 0.5 mL min−1)
tR 30.6 (S), 37.0 (R) min.
3H), 1.05–2.00 (m, 2H), 2.10–2.35 (m, 2H), 3.34 (s, 3H),
4.64 (dd, J=4.2, 11.4 Hz, 1H), 6.80–7.60 (m, 8H),
7.80–8.00 (m, 1H); 13C NMR l 13.7, 20.0, 28.2, 30.9,
71.2, 110.1, 121.2, 124.1, 125.9, 127.9, 128.3, 129.7,
133.0, 134.2, 135.0, 140.0, 145.2, 168.9; IR (neat) 3062,
2961, 1336, 1156 747, 633 cm−1; EIMS m/z (rel. inten-
sity) 328 (M+, 15), 263 (67), 133 (44), 132 (36), 91 (100).
Anal calcd for C18H20N2O2S; C, 65.83, H, 6.14, N, 8.53.
Found: C, 65.73, H, 6.44, N, 8.32; HPLC (Chiralcel
OD-H, hexane/i-PrOH=90:10, flow rate 0.5 mL min−1)
tR 28.1 (R), 35.2 (S) min.
Determination of absolute configuration of 7a and 7g
5.39. (S)-1-Methyl-2-[(1-phenylbutyl)thio]benzimidazole,
(S)-20
5.36. (S)-4,4-Dimethyl-2-pentanol, 17
The reaction as described in the preparation of 18 was
performed for 19 (75.4 mg, 0.502 mmol) to afforded
(S)-20 (83.4 mg, 56%): [h]2D0 −197 (c 1.04, CHCl3, 64%
A solution of (S)-propylene oxide (0.301 mL, 4.31
mmol) containing cat. copper iodide (12.3 mg, 0.0647
mmol) in diethyl ether was cooled to −30°C. To this
solution t-butylmagnesium chloride (1.82 mol L−1, solu-
tion in ether, 3.55 mL, 6.46 mmol) was added dropwise
over a period of 10 min. After stirring for 2 h, the
reaction was quenched with saturated aqueous NH4Cl
and extracted with CH2Cl2. The organic extracts were
dried over Na2SO4, and concentrated under reduced
pressure to leave a residue which was purified by
column chromatography (silica gel 30 g, CH2Cl2) to
afford 17 (341 mg, 68%) [h]2D5 +26.3 (c 0.638 EtOH)
lit.11 [h]2D5 −39.4 (c 2.25 EtOH, 98.4% ee (R)).
1
ee); Rf=0.29 (benzene); H NMR l 1.91 (t, J=7.2 Hz,
3H), 1.20–1.60 (m, 2H), 1.90–2.40 (m, 2H), 3.49 (s, 3H),
4.80–5.20 (m, 1H), 7.15–7.25 (m, 8H), 7.65–7.90 (m,
1H); 13C NMR l 13.9, 20.9, 30.0, 38.1, 52.6, 108.6,
118.4, 121.6, 121.9, 127.1, 127.3, 128.0, 128.1, 135.9,
141.1, 142.99, 149.9; IR (neat) 2958, 1358, 1152, 737
cm−1; EIMS m/z (rel. intensity) 296 (M+, 18), 164 (89),
91 (49), 49 (30), 28 (100). Anal calcd for C18H20N2S; C,
72.93, H, 6.80, N, 9.45. Found: C, 73.07, H, 6.76, N,
9.34. HPLC (Chiralcel OD-H, hexane/i-PrOH=95:5,
flow rate 0.5 mL min−1) tR 16.4 (S), 21.0 (R) min.
5.37. (R)-1-(Phenylmethyl)-2-[(1,3,3-trimethylbutyl)thio]-
benzimidazole, (R)-18
5.40. (S))-1-Methyl-2-[(1-phenylbutyl)sulfonyl]-
benzimidazole, (S)-7g
To a solution of (S)-4,4-dimethylpentanol 17 (124 mg,
1.07 mmol) in THF (3.0 mL) was added slowly diethyl
azodicarboxylate (0.397 mL, 2.57 mmol). After stirring
for 5 min, a solution of triphenylphosphine in THF (3.0
mL) and successively a solution of 1-benzylbenzimida-
zole-2-thiol (692 mg, 2.88 mmol) in THF (3.0 mL) were
A solution of sulfide (S)-20 (43.2 mg, 0.146 mmol) was
treated as in the preparation of (R)-7a to afford (S)-7g
(48.0 mg, 100%): [h]D20 −62.8 (c 0.946, CHCl3, 64% ee);
HPLC (Chiralcel OD-H, hexane/i-PrOH=95:5, flow
rate 1.0 mL min−1) tR 16.6 (R), 21.0 (S) min.

H. Sugimoto et al. / Tetrahedron: Asymmetry 14 (2003) 3043–3055
3055
Acknowledgements
Paradilla, R.; Mart´ınez, M. V.; Montero, C.; Viso, A. J.
Org. Chem. 2000, 65, 6462–6473.
4. (a) Mase, N.; Watanabe, Y.; Toru, T. Tetrahedron Lett.
1999, 40, 2797–2800; (b) Mase, N.; Watanabe, Y.; Toru,
T.; Kakumoto, T.; Hagiwara, T. J. Org. Chem. 2000, 65,
7083–7090.
5. For chiral relay in enantioselective reactions, see:
Corminboeuf, O.; Quaranta, L.; Renaud, P.; Liu, M.;
Jasperse, C. P.; Sibi, M. P. Chem. Eur. J. 2003, 9, 28–35.
6. Watanabe, Y.; Mase, N.; Furue, R.; Toru, T. Tetra-
hedron Lett. 2001, 42, 2981–2984.
This work was supported by a Grant-in-Aid for Scien-
tific Research (no.12650853) from the Ministry of Edu-
cation, Science, Sports and Culture of Japan and the
Tatematsu Foundation.
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7. LHMDS abstracted the benzyl proton instead of that a
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