Asymmetric conjugate addition of thiols to (E)-3-crotonoyloxazolidin-2-one by iron or cobalt/pybox catalyst

Article abstract of DOI:10.1016/j.tet.2008.01.121

The enantioselective conjugate addition of thiols to (E)-3-crotonoyloxazolidin-2-one was effectively catalyzed by the Fe(BF₄)₂·6H₂O/(S,S)-ip-pybox catalyst, and the addition product was obtained with up to a 95% ee. Furthe

Full text of DOI:10.1016/j.tet.2008.01.121

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 3488e3493
www.elsevier.com/locate/tet
Asymmetric conjugate addition of thiols to (E)-3-crotonoyloxazolidin-
-one by iron or cobalt/pybox catalyst
2
Motoi Kawatsura*, Yuji Komatsu, Masashi Yamamoto, Shuichi Hayase, Toshiyuki Itoh*
Department of Materials Science, Faculty of Engineering, Tottori University, Koyama, Tottori 680-8552, Japan
Received 13 January 2008; received in revised form 30 January 2008; accepted 31 January 2008
Available online 3 February 2008
Abstract
The enantioselective conjugate addition of thiols to (E)-3-crotonoyloxazolidin-2-one was effectively catalyzed by the Fe(BF
4 2 2
) $6H O/
(
also catalyzed the same reaction with a high enantioselectivity.
S,S)-ip-pybox catalyst, and the addition product was obtained with up to a 95% ee. Furthermore, the Co(ClO $6H O/(S,S)-ip-pybox catalyst
4
)
2
2
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Iron catalyst; Cobalt catalyst; Conjugate addition; Enantioselectivity; Thiol
1
. Introduction
On the other hand, iron is one of the most abundant and envi-
ronmentally friendly metals on the earth. During the past two de-
cades, some efficient organic transformations, which were
Conjugate addition is one of the most important bond form-
1
0
ing reactions in synthetic organic chemistry, and several types
of reactions including the asymmetric reaction of active meth-
ylene compounds have been attained using chiral Lewis acid
catalyzed by iron salts, were reported. Most of these reports
demonstrated carbonecarbon bond formations such as cou-
pling, cycloaddition, or polymerization reactions. Our group
also reported some iron-catalyzed reactions, i.e., cycloaddition
reactions and Michael addition-type reactions in an organic or
1
e3
catalysts or chiral organocatalysts.
On the other hand, the
asymmetric conjugate addition of thiols to a,b-unsaturated
4
substrates is also a very useful reaction because it produces
11
ionic liquid solvent system. However, until recently, iron
was relatively underrepresented in the field of asymmetric cata-
5
optically active compounds, such as pharmaceuticals. How-
1
2,13
ever, even this type of reaction is a difficult process, and there
are only limited examples of the transition metal-catalyzed
enantioselective addition of thiols to (E)-3-crotonoyloxazol-
idin-2-one. The first example was reported by Kanemasa
et al. in 1999; Ni/DBFOX catalyzed the highly enantioselective
reactions of several thiols to (E)-3-crotonoyloxazolidin-2-one.
After their pioneering work, three groups independently dem-
onstrated this kind of reaction using chiral Yb, Hf, and Sc
catalysts.
lysts
compared to other transition metals for chiral com-
plexes such as palladium, rhodium, ruthenium, etc. Therefore,
we believe that the use of iron required for asymmetric organic
syntheses and the enantioselective construction of the carbone
heteroatom bond is one of the most challenging topics in this
field. From this perspective, the iron-catalyzed conjugate addi-
tion of thiols to a,b-unsaturated compounds still remains unre-
solved. Recently, we discovered that the iron/pybox catalyst
exhibits a high enantioselectivity during the conjugate addition
6
7
8
9
1
4
of thiols to the (E)-3-crotonoyloxazolidin-2-one. During the
course of this study, we found that a cobalt salt with a pybox li-
gand also catalyzes the same reaction with similar enantiomeric
excesses. In this paper, we report the chiral iron and cobalt-cata-
lyzed asymmetric conjugate addition of aromatic thiols to the
(E)-3-crotonoyloxazolidin-2-one.
*
Corresponding authors. Tel./fax: þ81 857 31 5179.
E-mail addresses: kawatsur@chem.tottori-u.ac.jp (M. Kawatsura), titoh@
chem.tottori-u.ac.jp (T. Itoh).
0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.01.121

M. Kawatsura et al. / Tetrahedron 64 (2008) 3488e3493
3489
2
. Results and discussion
Table 1
Iron-catalyzed asymmetric conjugate addition of benzenethiol (1a) to (E)-3-
a
crotonoyloxazolin-2-one (2)
2
.1. Iron/pybox-catalyzed reaction
b
b,c
Entry [Fe]
L
Additive Temp/time
h)
Yield
(%)
ee
(%)
(
The screening of an effective iron catalyst for the conjugate
1
2
3
4
5
6
7
8
9
FeCl
FeCl
2
L1
L1
L1
L1
L2
L3
L1
d
d
d
d
d
d
d
rt/24
rt/24
rt/24
rt/24
rt/24
rt/24
79
69
90
74
92
95
53
17
40
66
0
addition of benzenethiol (1a) to (E)-3-crotonoyloxazolidin-2-
one (2) was performed using various iron salts (FeCl , FeCl ,
Fe(BF ) , Fe(ClO ) , Fe(ClO ) , Fe(OAc) , Fe(acac) , etc.),
3
2
3
Fe(ClO
4 2 2
) $6H O
4
2
4 2
4 3
2
2
Fe(BF ) $6H O
4
2
2
chiral ligands (BINAP, MOP, phox, pybox, box, Jacobsen li-
Fe(BF ) $6H O
4
4
4
4
4
2
2
2
2
2
2
2
2
2
2
1
5
gand, etc. ), and solvents (toluene, THF, diethyl ether, diox-
ane, dichloromethane, acetonitrile, dimethylforamide, etc.).
We discovered that the iron(II) salt with the bisoxazoline-based
chiral ligand in THF exhibited a better reactivity and enantiose-
lectivity than the other iron catalysts and solvents (Scheme 1).
For example, iron(II) chloride with the chiral (S,S)-ip-pybox
Fe(BF
Fe(BF
Fe(BF
Fe(BF
)
)
)
)
$6H
$6H
$6H
$6H
O
O
O
O
0
ꢁ
ꢁ
ꢁ
ꢀ20 C/150 86
86
90
90
˚
L1 MS 4 A
˚
L1 MS 4 A
ꢀ20 C/24
86
93
d
ꢀ20 C/72
a
1
6
All reactions were carried out with 1a (0.75 mmol), 2 (0. 50 mmol),
0 mol % iron salt, and 10 mol % chiral ligand in 0.8 mL of THF under
nitrogen.
1
1
7
b
ligand (L1) gave the addition product 3a in 79% yield with
3% ee (entry 1 in Table 1). On the other hand, iron(III) chlo-
Values for ee and yields are for pure, isolated compounds and are an aver-
age of two runs.
5
c
Values of ee were determined by chiral HPLC using Daicel CHIRALPAK
AD-H (hexane/2-propanol¼5/1).
ride with L1 gave the product 3a with 17% ee (entry 2). Based
on these results, it is obvious that the iron(II) salts are promis-
ing catalysts for the asymmetric conjugate addition of thiol 1a
to the a,b-unsaturated amide 2. Therefore, we attempted to
evaluate the iron(II) salts, switching the catalyst from FeCl2
to Fe(ClO ) $6H O increased the chemical yield of 3a up to
d
[
Fe] of 3 mol % and L1 were used.
Fortunately a significant acceleration was obtained when the re-
1
9
˚
action was conducted in the presence of molecular sieves 4 A,
and the enantioselectivity also slightly increased up to 90% ee
entry 8). Furthermore, it was found that the reaction proceeded
4
2
2
9
4
0%, while the enantioselectivity significantly decreased to
0% ee (entry 3). Optimization of the iron(II) salts concluded
(
with an excellent enantioselectivity using only 3 mol % of the
catalyst, though a longer reaction time was needed (entry 9).
Results of the asymmetric conjugate addition of various
types of thiols by this iron/ip-pybox catalyst system (Scheme
that combination of iron(II) tetrafluoroborate Fe(BF ) $6H O
4
2
2
with the (S,S)-ip-pybox ligand (L1) was the best catalyst, and
the desired addition product 3a was obtained in 74% yield
with 66% ee (entry 4). Interestingly, the reaction using other
chiral bisoxazoline-based ligands, such as (S,S)-phe-pybox
2
) are summarized in Table 2. All reactions were carried out
in the presence of Fe(BF ) $6H O (10 mol %), ip-pybox
(
(
L2) and (S,S)-ip-phebox (L3), showed no enantioselectivity
entries 5 and 6). These results suggest that both the isopropyl
4 2
2
˚
ꢁ
(
10 mol %), and MS 4 A in THF at ꢀ20 C. The reactions of
1
8
the aromatic thiols exhibited both high yields and enantiomeric
excesses (Table 2, entries 1e5). The highest enantioselectivity
group in the pybox ligand and pyridyl backbone are essential
for realizing a highly enantioselective reaction. Based on these
results, we concluded that the chiral iron catalyst with (S,S)-ip-
pybox (L1) is the most effective Lewis acid iron catalyst for the
asymmetric conjugate addition of benzenethiol 1a to 2. The
higher enantioselectivity (86% ee) was attained at a lower tem-
(95% ee) was obtained for the reaction of the sterically
hindered 2-methylbenzenethiol (1d) (entry 3). This type of
steric effect on enantioselectivity was previously reported by
4
a,b
Tomioka et al.
It should be emphasized that an excellent
ꢁ
enantioselectivity was obtained even when the reaction was
performed using 3 mol % of the chiral iron catalyst, though it
required a longer reaction time to complete the reaction (entry
6). Unfortunately, it was found that our catalyst system was not
effective for the reaction of an alkyl thiol, such as benzyl
mercaptan (1g), and it produced 3g with only a 24% ee
perature (ꢀ20 C), while the reaction rate significantly de-
creased and it took 150 h to complete the reaction (entry 7).
PhSH
1a
10 mol% [M]
PhS
O
O
1
0 mol% L
+
THF
Me *
N
O
2
0
O
O
(entry 7).
3
a
Me
N
O
2
1
1
0 mol% [M]
O
R
1
SH
b-g
RS
Me
O
0 mol% L1
N
O
MS 4A, –20 °C
THF
+
2
O
O
N
3b-g
(L1 = (S,S)-ip-pybox)
O
R
O
X
N
N
N
N
1b: R = p-Methoxyphenyl
1
c: R = p-Chlorophenyl
d: R = o-Tolyl
1e: R = p-Tolyl
1f: R = 2-Naphthyl
1g: R = Benzyl
R
1
L1: X = N, R = iPr {(S,S)-ip-pybox}
L2: X = N, R = Ph {(S,S)-phe-pybox}
L3: X = C, R = iPr {(S,S)-ip-phebox}
L4: inda-pybox
Scheme 1.
Scheme 2.

3490
M. Kawatsura et al. / Tetrahedron 64 (2008) 3488e3493
Table 2
increased the enantioselectivity up to 78% ee (entry 6). For this
Co(ClO ) $6H O catalyzed reaction, other pybox type ligands
4
Fe(BF )
a
2
/ip-pybox-catalyzed asymmetric conjugate addition of thiols 1beg
4 2
2
to 2
did not show any enantioselectivities similar to the iron-catalyzed
reaction (entries 7e9). These results strongly suggest that both the
pyridyl backbone and isopropyl group on the oxazoline ring are
essential for realizing a high enantioselective reaction. To attain a
much higher enantioselectivity, the reaction was conducted at a
ꢁ
b
Yield (%)
b,c
ee (%)
Entry
1
Temp ( C)/time (h)
1
2
3
4
5
1b
1c
1d
1e
1f
ꢀ20/24
ꢀ20/24
ꢀ20/108
ꢀ20/24
ꢀ20/72
ꢀ20/168
ꢀ20/48
84
99
92
87
96
72
53
85
87
95
90
89
91
24
ꢁ
lowertemperature (ꢀ20 C), butboth the reaction rate and enantio-
d
˚
selectivity decreased. Fortunately, the addition of MS 4 A again
6
1f
1g
7
increased both these factors, and thus we succeeded in obtaining
the addition product in 88% yield with 91% ee (entry 11). It was
further found that the reaction proceeded without losing any enan-
tioselectivity when a 5 mol % cobalt catalyst was used, though a
longer reaction time (168 h) was needed (entry 12).
a
All reactions were carried out with 1 (0.75 mmol), 2 (0.50 mmol),
˚
0 mol % iron salt, 10 mol % chiral ligand, and MS 4 A (17 mg) in 0.8 mL
1
of THF under nitrogen.
b
Values for ee and yields are for pure, isolated compounds and are an aver-
age of two runs.
c
We also examined the reaction with various types of thiols
using this cobalt/ip-pybox catalyst system (Scheme 2), and
these results are summarized in Table 4. All reactions were car-
Values of ee were determined by chiral HPLC.
d
4 2 2
Fe(BF ) $6H O of 3 mol % and (S,S)-ip-pybox (L1) were used.
2
.2. Cobalt/pybox-catalyzed reaction
ꢁ
ried out with a 10 mol % catalyst at ꢀ20 C, and the reaction
was monitored by TLC. The reactions of several aromatic thiols
smoothly proceeded, and the addition products were obtained
with over 85% yields (Table 4, entries 1e5). However, we found
that the enantioselectivity was strongly affected by the elec-
tronic effects of the substituent on the aromatic ring. The reac-
tion with 4-methoxybenzenethiol (1b) gave a result similar to
the reaction with 1a, but the enantioselectivity for the reaction
with 4-chlorophenylbenzenethiol (1c) decreased to 40% ee
During the course of the iron/pybox-catalyzed reaction, we
found that a cobalt salt with a chiral ligand also catalyzes the
same reaction with high enantiomeric excesses. Based on the re-
sults of the iron/pybox-catalyzed reaction, we examined several
cobalt/pybox catalysts for the conjugate addition of 1a to 2
(
Scheme 1). As shown in Table 3, the trend in the enantioselectivity
was very similar to the results for the iron/pybox-catalyzed reac-
tion. Some cobalt salts exhibited a good reactivity and produced
the addition product 3in good isolated yield. However, the enantio-
(entries 1 and 2). Other aromatic thiols, such as 2-naphthylthiol
(1f) and 4-methylbenzenethiol (1e), also exhibited both high
mericexcesswaslowerthan34% eewhenCo(acac) , Co(acac) ,or
3
CoI wasused(Table 3,entries1e3). A higherenantiomericexcess
2
2
yields and enantiomeric excesses (entries 3 and 4). The highest
enantioselectivity (95% ee) was obtained for the reaction of the
sterically hindered 2-methylbenzenethiol (1d), though it re-
quired a longer reaction time (144 h) to complete the reaction
(entry 5). Unfortunately, it was found that this cobalt catalyst
system was not effective for the reaction of an alkyl thiol,
such as benzyl mercaptan (1g), and it produced only a 39%
product with 0% ee (entries 6 and 7).
(62% ee) was observed for the reaction using Co(OAc) , but the
isolated yield was slightly lower (67%) (entry 4). Finally, we found
2
that Co(ClO ) $6H O with (S,S)-ip-pybox is the best combination,
4
2
2
and 3a was obtained in 91% yield with 62% ee (entry 5). Again,
˚
the addition of molecular sieves 4 A (MS 4 A) effectively
˚
Table 3
Cobalt-catalyzed asymmetric conjugate addition of benzenethiol (1a) to (E)-3-
crotonoyloxazolin-2-one (2)
Table 4
Cobalt/pybox-catalyzed asymmetric conjugate addition of thiols 1beg to 2
a
a
ꢁ
b
c
Entry [Co]
L
Additive Temp ( C)/
time (h)
Yield
(%)
ee
(%)
ꢁ
b
Yield (%)
c
ee (%)
Entry
1
Temp ( C)/time (h)
1
2
3
4
5
6
7
a
1b
1c
1f
ꢀ20/96
ꢀ20/72
ꢀ20/120
ꢀ20/96
ꢀ20/144
ꢀ20/48
25/24
85
90
88
87
85
0
91
40
87
88
95
d
0
1
2
3
4
5
6
7
8
9
1
1
1
Co(acac)
Co(acac)
CoI
Co(OAc)
3
L1
L1
L1
L1
L1
L1
L2
L3
L4
L1
L1
L1
None
None
None
None
None
25/24
25/24
25/24
64
68
85
67
91
97
74
96
71
70
88
86
28
34
34
62
66
78
0
2
2
1e
1d
1g
1g
2
25/24
25/24
Co(ClO
Co(ClO
Co(ClO
Co(ClO
Co(ClO
Co(ClO
Co(ClO
Co(ClO
4
4
4
4
4
4
4
4
)
2
2
2
2
2
2
2
2
$6H
$6H
$6H
$6H
$6H
$6H
$6H
$6H
2
2
2
2
2
2
2
2
O
O
O
O
O
O
O
O
˚
)
)
)
)
)
)
)
MS 4 A
None
None
None
None
25/24
25/24
39
All reactions were carried out with 1 (0.75 mmol), 2 (0.50 mmol),
˚
25/24
25/24
0
4 2 2
Co(ClO ) $6H O (0.05 mmol), (S,S)-ip-pybox (0.05 mmol), and MS 4 A
0
(
19 mg) in 0.8 mL of THF under nitrogen.
b
0
1
2
a
ꢀ20/150
ꢀ20/72
ꢀ20/168
47
91
90
˚
Isolated yield by silica gel column chromatography.
Values of ee were determined by chiral HPLC: Daicel CHIRALCEL OD-H
MS 4 A
˚
MS 4 A
c
d
(
hexane/2-propanol¼19/1) for 3b and 3deg; Daicel CHIRALPAK AD-H
hexane/2-propanol¼5/1) for 3c.
All reactions were carried out with 1a (0.75 mmol), 2 (0.50 mmol),
(
10 mol % cobalt salt, and 10 mol % chiral ligand in 0.8 mL of THF under ni-
trogen unless otherwise noted.
3. Conclusion
b
Isolated yield by silica gel column chromatography.
Values of ee were determined by chiral HPLC using Daicel CHIRALPAK
c
In conclusion, we succeeded in demonstrating the iron or
cobalt salt-catalyzed asymmetric conjugate addition of thiols
AD-H (hexane/2-propanol¼5/1).
d
Co(ClO
4
)
2
$6H
2
O of 5 mol % and L1 were used.

M. Kawatsura et al. / Tetrahedron 64 (2008) 3488e3493
3491
with a,b-unsaturated amide; both the iron and cobalt catalysts,
which were prepared from Fe(BF ) $6H O or Co(ClO ) $6H O
with the (S,S)-ip-pybox ligand, respectively, exhibited excellent
enantioselectivities and the desired addition products were
obtained in good yields.
3.74e3.82 (m, 1H), 3.90e4.01 (m, 2H), 4.33e4.44 (m, 2H),
1
3
7.23e7.33 (m, 3H), 7.44e7.47 (m, 2H).
(100 MHz, CDCl ) 21.17, 38.86, 42.20, 42.33, 61.98,
C NMR
4
2
2
4 2
2
3
127.25, 128.80, 132.68, 134.00, 153.27, 170.90. Colorless
2
4
6
25
oil; [a]D ꢀ12.70 (c 1.26, CHCl ) {lit. [a]D ꢀ11.05 (c
3
1.23, CHCl )} {90% ee estimated on the basis of the HPLC
using a chiral column (Daicel CHIRALPAK AD-H, hexane/
3
4
. Experimental section
i-PrOH¼5/1 v/v, flow rate¼1.0 mL/min, tR(R)¼11 min,
4
.1. General methods
t (S)¼16 min)}.
R
All manipulations were carried out under a nitrogen atmo-
sphere. Nitrogen gas was dried by passage through P O .
NMR spectra were recorded on a JEOL JNM MH400 spectro-
4.2.2. (ꢀ)-(S)-3-[3-(p-Methoxyphenylthio)butanoyl]-2-
6
oxazolidinone (3b)
2
5
1
H NMR (400 MHz, CDCl ) 1.30 (d, J¼6.8 Hz, 3H), 3.06
3
1
meter (400 MHz for H and 100 MHz for C) or JNM MH
13
(dd, J¼17.0, 7.0 Hz, 1H), 3.24 (dd, J¼16.8, 7.0 Hz, 1H),
3.58e3.61 (m, 1H), 3.80 (s, 3H), 3.96 (t, J¼7.9 Hz, 2H), 4.37
13
1 13
00 spectrometer (500 MHz for H and 125 MHz for C).
5
Chemical shifts are reported in d ppm referenced to an internal
(t, J¼7.9 Hz, 2H), 6.85 (d, J¼8.8 Hz, 2H), 7.43 (d, J¼8.8 Hz,
1
SiMe standard for H NMR. Residual chloroform (d 77.0 for
2H). C NMR (100 MHz, CDCl ) 21.09, 39.84, 42.19, 42.38,
4
3
1
3
13
C) was used as internal reference for C NMR. H and
1
13
C
NMR spectra were recorded in CDCl at 25 C unless otherwise
55.27, 62.01, 114.34, 123.80, 136.24, 153.30, 159.72, 171.08.
25
ꢁ
25
6
Colorless oil; [a]D ꢀ6.70 (c 2.13, CHCl ) {lit. [a] ꢀ5.95
3
3
D
noted. All iron salts and chiral ligands include Fe(BF ) $6H O,
2
(c 2.05, CHCl )} {86% ee estimated on the basis of the HPLC
3
4
2
Co(ClO ) $6H O, 2,6-bis[(4S)-(ꢀ)-isopropyl-2-oxazolin-2-
using a chiral column (Daicel CHIRALCEL OD-H, hexane/
i-PrOH¼9/1 v/v, flow rate¼1.0 mL/min, tR(R)¼34 min,
4
2
2
yl]pyridine {(S,S)-ip-pybox, L1}, 2,6-bis[(4S)-(ꢀ)-phenyl-2-
oxazolin-2-yl]pyridine {(S,S)-phe-pybox, L2}, and (ꢀ)-2,6-
t (S)¼40 min)}.
R
0
0
bis[2-{3aS-(2(3 aR*,8 aS*),3aa,8aa)-3a,8a-dihydro-8H-in-
deno[1,2-d]oxazole}]pyridine {inda-pybox (L4)} were pur-
chased from Aldrich, and used without further purification.
The following thiols are commercially available: thiophenol;
o-tolylthiol; p-tolylthiol; p-methoxythiophenol; p-chlorothio-
phenol; 2-naphthylthiol; benzylthiol. (E)-3-Crotonoyloxazo-
4.2.3. (ꢀ)-(S)-3-[3-(p-Chlorophenylthio)butanoyl]-2-
9
b
oxazolidinone (3c)
H NMR (500 MHz, CDCl ) 1.35 (d, J¼6.9 Hz, 3H), 3.12
1
3
(dd, J¼17.0, 6.9 Hz, 1H), 3.26 (dd, J¼17.0, 6.9 Hz, 1H),
3.71e3.76 (m, 1H), 3.96e3.99 (d, J¼7.8 Hz, 2H), 4.40 (t,
13
2
1
lin-2-one (2)
and 1,3-bis[(4S)-isopropyl-2-oxazolin-2-
J¼7.8 Hz, 2H), 7.27 (d, J¼7.6 Hz, 2H), 7.39 (d, J¼7.6 Hz,
2
2
yl]benzene {(S,S)-ip-phebox (L3)} were prepared according
to the literatures. Other reagents and solvents were purchased
from common commercial sources and were used as received
or purified by distillation from appropriate drying agents.
2H). C NMR (125 MHz, CDCl ) 21.16, 39.24, 42.17, 42.40,
3
62.06, 129.02, 132.54, 133.57, 134.21, 153.31, 170.84. Color-
2
5
9b
20
less powder; [a]D ꢀ16.47 (c 2.15, CHCl ) {lit. [a]D ꢀ21
3
(c 1.0, CH Cl )} {87% ee estimated on the basis of the HPLC
2
2
using a chiral column (Daicel CHIRALPAK AD-H, hexane/
i-PrOH¼5/1 v/v, flow rate¼1.0 mL/min, tR(R)¼19 min,
4
.2. General procedure of iron-catalyzed conjugate addition
of thiols to (E)-3-crotonoyloxazolin-2-one (entry 8 in Table 1)
t (S)¼23 min)}.
R
The reaction conditions and results are shown in Tables 1 and
. A typical procedure is given for the reaction of (ꢀ)-(S)-3-(3-
4.2.4. (ꢀ)-(S)-3-(3-o-Tolylthiobutanoyl)-2-oxazolidinone
6
2
(3d)
1
phenylthiobutanoyl)-2-oxazolidinone (3a) (Table 1, entry 8). To
a solution of Fe(BF ) $6H O (16.9 mg, 0.05 mmol), (S,S)-ip-
pybox (15.1 mg, 0.05 mmol), (E)-3-crotonoyl-2-oxazolidinone
H NMR (500 MHz, CDCl ) 1.35 (d, J¼6.9 Hz, 3H), 2.41 (s,
3
3H), 3.13 (dd, J¼17.0, 6.9 Hz, 1H), 3.24 (dd, J¼17.0, 6.9 Hz,
1H), 3.74e3.78 (m, 1H), 3.89 (t, J¼7.8 Hz, 2H), 4.33 (t,
4
2
2
1
3
˚
(
was added benzenethiol (1a) (78 mg, 0.75 mmol), then stirred at
2) (77.6 mg, 0.50 mmol), and MS 4 A (17 mg) in THF (0.8 mL)
J¼7.8 Hz, 2H), 7.12e7.19 (m, 3H), 7.41e7.43 (m, 2H).
C
NMR (125 MHz, CDCl ) 20.78, 21.10, 38.24, 42.34, 42.36,
3
ꢁ
ꢀ
20 C for 24 h. The reaction mixture was quenched with satd
NH Cl, then extracted with THF (3ꢂ2 mL). The combined or-
62.01, 126.27, 127.24, 130.31, 132.68, 133.68, 140.36,
2
6
153.29, 171.01. Colorless oil; [a] ꢀ29.95 (c 2.13, CHCl )
4
D
3
6
25
D
ganic layers were dried over MgSO and concentrated in vacuo.
4
{lit. [a] ꢀ30.33 (c 2.09, CHCl )} {95% ee estimated on the
3
The residue was chromatographed on silica gel (hexane/
EtOAc¼7/3) to give 114 mg (86%) of product 3a. The enantio-
meric purity was determined by chiral HPLC analysis with a
chiral stationary phase column.
basis of the HPLC using a chiral column (Daicel CHIRALCEL
OD-H, hexane/i-PrOH¼19/1 v/v, flow rate¼1.0 mL/min,
t (R)¼32 min, t (S)¼45 min)}.
R
R
4
(3e)
.2.5. (ꢀ)-(S)-3-(3-p-Tolylthiobutanoyl)-2-oxazolidinone
6
4
.2.1. (ꢀ)-(S)-3-(3-Phenylthiobutanoyl)-2-oxazolidinone
6
1
(
3a)
H NMR (500 MHz, CDCl ) 1.26 (d, J¼6.9 Hz, 3H), 2.25 (s,
3
1
H NMR (400 MHz, CDCl ) 1.36 (d, J¼6.6 Hz, 3H), 3.14
3H), 3.03 (dd, J¼17.0, 6.9 Hz, 1H), 3.17 (dd, J¼17.0, 6.9 Hz,
1H), 3.59e3.64 (m, 1H), 3.88 (t, J¼7.8 Hz, 2H), 4.30 (t,
3
(
dd, J¼17.2, 7.0 Hz, 1H), 3.27 (dd, J¼16.9, 7.0 Hz, 1H),

3492
M. Kawatsura et al. / Tetrahedron 64 (2008) 3488e3493
J¼7.8 Hz, 2H), 7.04 (d, J¼7.8 Hz, 2H), 7.29 (d, J¼7.8 Hz, 2H).
Acknowledgements
1
3
C NMR (125 MHz, CDCl ) 21.03, 21.16, 39.24, 42.22, 42.37,
3
6
2.00, 129.59, 130.04, 133.56, 137.61, 153.28, 171.03. Colorless
6
This work was supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports,
Science and Technology, Japan.
2
4
25
D
oil; [a] ꢀ17.74 (c 2.65, CHCl ) {lit. [a] ꢀ20.85 (c 2.67,
D
3
CHCl )}{90% ee estimated onthe basis of the HPLC using a chi-
3
ral column (Daicel CHIRALCEL OD-H, hexane/i-PrOH¼19/1
v/v, flow rate¼1.0 mL/min, t (R)¼37 min, t (S)¼46 min)}.
R
R
References and notes
4
.2.6. (ꢀ)-(S)-3-[3-(2-Naphthylthio)butanoyl]-2-
1
. For reviews, see: (a) Christoffers, J.; Baro, A. Angew. Chem., Int. Ed. 2003,
42, 1688e1690; (b) Sibi, M. P.; Manyem, S. Tetrahedron 2000, 56, 8033e
6
oxazolidinone (3f)
1
8
061; (c) Christoffers, J. Eur. J. Org. Chem. 1998, 1259e1266; (d) Berner,
H NMR (500 MHz, CDCl ) 1.41 (d, J¼6.9 Hz, 3H), 3.17
3
O. M.; Tedeschi, L.; Enders, D. Eur. J. Org. Chem. 2002, 1877e1894; (e)
Krause, N.; Hoffmann-R o¨ der, A. Synthesis 2001, 171e196; (f) Dalko,
P. I.; Moisan, L. Angew. Chem., Int. Ed. 2004, 43, 5138e5175.
(
(
7
1
6
1
dd, J¼17.0, 6.6 Hz, 1H), 3.34 (dd, J¼17.0, 6.6 Hz, 1H), 3.84
t, J¼7.8 Hz, 2H), 3.85e3.94 (m, 1H), 4.25 (t, J¼7.8 Hz, 2H),
.45e7.54 (m, 3H), 7.76e7.81 (m, 3H), 7.94 (d, J¼1.79 Hz,
2
. For selected recent examples using organometallic catalysts, see: (a)
Duguet, N.; Harrison-Marchand, A.; Maddaluno, J.; Tomioka, K. Org.
Lett. 2006, 8, 5745e5748; (b) Yanagita, H.; Kodama, K.; Kanemasa, S.
Tetrahedron Lett. 2006, 47, 9353e9357; (c) Althaus, M.; Bonaccorsi,
C.; Mezzetti, A.; Santoro, F. Organometallics 2006, 25, 3108e3110; (d)
Chen, C.; Zhu, S.-F.; Wu, X.-Y.; Zhou, Q.-L. Tetrahedron: Asymmetry
2006, 17, 2761e2767; (e) Liu, T.-Y.; Li, R.; Chai, Q.; Long, J.; Li,
B.-J.; Wu, Y.; Ding, L.-S.; Chen, Y.-C. Chem.dEur. J. 2007, 13, 319e
1
3
H). C NMR (125 MHz, CDCl ) 21.29, 39.00, 42.32, 42.44,
3
1.94, 126.22, 126.49, 127.44, 127.60, 128.37, 130.16,
31.47, 131.61, 132.35, 133.53, 153.27, 170.96. Colorless pow-
2
5
6
25
D
der; [a] ꢀ17.5 (c 2.86, CHCl ) {lit. [a] ꢀ17.27 (c 2.90,
D
3
CHCl )} {89% ee estimated on the basis of the HPLC using
3
a chiral column (Daicel CHIRALCEL OD-H, hexane/
i-PrOH¼19/1 v/v, flow rate¼1.0 mL/min, t (R)¼50 min,
3
27; (f) Sibi, M. P.; Soeta, T. J. Am. Chem. Soc. 2007, 129, 4522e
523; (g) Zhao, Q.-L.; Wang, L.-L.; Kwong, F. Y.; Chan, A. S. C. Tetra-
R
4
t (S)¼59 min)}.
R
hedron: Asymmetry 2007, 18, 1899e1905.
3
. For selected recent examples using organocatalysts, see: (a) Mase, N.;
Watanabe, K.; Yoda, H.; Takabe, K.; Tanaka, F.; Barbas, C. F., III.
J. Am. Chem. Soc. 2006, 128, 4966e4967; (b) Enders, D.; N u¨ ttl,
M. R. M.; Grondal, C.; Raabe, G. Nature 2006, 441, 861e863; (c) Huang,
H.; Jacobsen, E. N. J. Am. Chem. Soc. 2006, 128, 7170e7171; (d) Xie,
J.-W.; Yue, L.; Chen, W.; Du, W.; Zhu, J.; Deng, J.-G.; Chen, Y.-C.
Org. Lett. 2007, 9, 413e415; (e) Palomo, C.; Vera, S.; Mielgo, A.;
G o´ mez-Bengoa, E. Angew. Chem., Int. Ed. 2006, 45, 5984e5987; (f)
Xiong, Y.; Wen, Y.; Wang, F.; Gao, B.; Liu, X.; Huang, X.; Feng, X.
Adv. Synth. Catal. 2007, 349, 2156e2166; (g) Gu, L.-Q.; Zhao, G.
Adv. Synth. Catal. 2007, 349, 1629e1632; (h) Shi, M.; Lei, Z.-Y.; Zhao,
M.-X.; Shi, J.-W. Tetrahedron Lett. 2007, 48, 5743e5746; (i) Chen, H.;
Wang, Y.; Wei, S.; Sun, J. Tetrahedron: Asymmetry 2007, 18, 1308e
4
.2.7. (ꢀ)-(S)-3-(3-Benzylthiobutanoyl)-2-oxazolidinone
6
(
3g)
1
H NMR (500 MHz, CDCl ) 1.33 (d, J¼6.4 Hz, 3H), 3.03e
3
3
.07 (m, 1H), 3.22e3.29 (m, 2H), 3.77 (d, J¼13.3 Hz, 1H), 3.80
(
d, J¼13.3 Hz, 1H), 3.93e3.99 (m, 2H), 4.33e4.37 (m, 2H),
1
3
.20e7.34 (m, 5H). C NMR (125 MHz, CDCl ) 21.48,
7
3
1
3
5.14, 35.46, 42.27, 42.31, 61.93, 126.79, 128.32, 128.72,
2
38.30, 153.26, 170.80. Colorless oil; [a] ꢀ5.87 (c 2.25,
0
D
6
25
D
CHCl ) {lit. [a] ꢀ3.77 (c 2.28, CHCl )} {17% ee estimated
3
3
on the basis of the HPLC using a chiral column (Daicel CHIR-
ALCEL OD-H, hexane/i-PrOH¼19/1 v/v, flow rate¼1.0 mL/
min, t (R)¼48 min, t (S)¼58 min)}.
1
312; (j) Xie, J.-W.; Chen, W.; Li, R.; Zeng, M.; Du, W.; Yue, L.; Chen,
Y.-C.; Wu, Y.; Zhu, J.; Deng, J.-G. Angew. Chem., Int. Ed. 2007,
6, 389e392; (k) Liu, K.; Cui, H.-F.; Nie, J.; Dong, K.-Y.; Li, X.-J.; Ma,
R
R
4
J.-A. Org. Lett. 2007, 9, 923e925.
4
. (a) Nishimura, K.; Ono, M.; Nagaoka, Y.; Tomioka, K. J. Am. Chem. Soc.
4
.3. General procedure of cobalt-catalyzed conjugate
1
997, 119, 12974e12975; (b) Emori, E.; Arai, T.; Sasai, H.; Shibasaki, M.
addition of thiols to (E)-3-crotonoyloxazolin-2-one
J. Am. Chem. Soc. 1998, 120, 4043e4044; (c) Saito, M.; Nakajima, M.;
Hashimoto, S. Tetrahedron 2000, 56, 9589e9594; (d) Nishimura, K.;
Tomioka, K. J. Org. Chem. 2002, 67, 431e434; (f) Wynberg, H.; Greijda-
nus, B. J. Chem. Soc., Chem. Commun. 1978, 427e428; (g) Kobayashi,
N.; Iwai, K. J. Am. Chem. Soc. 1978, 100, 7071e7072; (h) Hiemstra,
H.; Wynberg, H. J. Am. Chem. Soc. 1981, 103, 417e430; (i) Marigo,
M.; Schulte, T.; Franz e´ n, J.; Jørgensen, K. A. J. Am. Chem. Soc. 2005,
(
entry 11 in Table 3)
The reaction conditions and results are shown in Tables 3
and 4. A typical procedure is given for the reaction of (ꢀ)-
S)-3-(3-phenylthiobutanoyl)-2-oxazolidinone (3a) (Table 3,
entry 11). To a solution of Co(ClO ) $6H O (18.4 mg,
(
4
2
2
1
27, 15710e15711.
. For example, see: Dike, S. Y.; Ner, D. H.; Kumar, A. Synlett 1991, 443e444.
6. Kanemasa, S.; Oderaotoshi, Y.; Wada, E. J. Am. Chem. Soc. 1999, 121,
675e8676.
7. Kobayashi, S.; Ogawa, C.; Kawamura, M.; Sugiura, M. Synlett 2001,
83e985.
0.05 mmol), (S,S)-ip-pybox (15.1 mg, 0.05 mmol), (E)-3-cro-
˚
tonoyl-2-oxazolidinone (2) (78 mg, 0.50 mmol), and MS 4 A
5
8
(
17 mg) in THF (0.8 mL) was added benzenethiol (1a)
ꢁ
(
tion mixture was quenched with satd NH Cl, then extracted
78 mg, 0.75 mmol) at ꢀ20 C, then stirred for 72 h. The reac-
9
4
8
. Matsumoto, K.; Watanabe, A.; Uchida, T.; Ogi, K.; Katsuki, T. Tetra-
hedron Lett. 2004, 45, 2385e2388.
with ether (3ꢂ2 mL). The combined organic layers were dried
over MgSO and concentrated in vacuo. The residue was chro-
4
9. (a) Sauerland, S. J. K.; Kiljunen, E.; Koskinen, A. M. P. Tetrahedron Lett.
006, 47, 1291e1293; (b) Abe, A. M. M.; Sauerland, S. J. K.; Koskinen,
2
matographed on silica gel (hexane/EtOAc¼7/3) to give
A. M. P. J. Org. Chem. 2007, 72, 5411e5413.
1
17 mg (88%) of a mixture of conjugate adducts 3a. The enan-
1
0. Bolm, C.;Legros, J.;LePaih, J.; Zani, L. Chem. Rev. 2004, 104, 6217e6254.
1. (a) Ohara, H.; Kudo, K.; Itoh, T.; Nakamura, M.; Nakamura, E. Hetero-
cycles 2000, 52, 505e510; (b) Ohara, H.; Itoh, T.; Nakamura, M.;
Nakamura, E. Chem. Lett. 2001, 624e625; (c) Ohara, H.; Kiyokane, H.;
tiomeric purity was determined by chiral HPLC analysis with
a chiral stationary phase column (Daicel CHIRALPAK
AD-H).
1

M. Kawatsura et al. / Tetrahedron 64 (2008) 3488e3493
3493
Itoh, T. Tetrahedron Lett. 2002, 43, 3041e3044; (d) Itoh, T.; Kawai, K.;
Hayase, S.; Ohara, H. Tetrahedron Lett. 2003, 44, 4081e4084; (e) Uehara,
H.; Nomura, S.; Hayase, S.; Kawatsura, M.; Itoh, T. Electrochemistry
16. The reaction without iron or cobalt salt also proceed and gave the addition
product 3a in 52% isolated yield, but the enantioselectivity was 0% ee.
17. (a) Nishiyama, H.; Sakaguchi, H.; Nakamura, T.; Horihata, M.; Kondo,
M.; Itoh, K. Organometallics 1989, 8, 846e848; (b) Nishiyama, H.;
Kondo, M.; Nakamura, T.; Itoh, K. Organometallics 1991, 10, 500e
508; (c) Desimoni, G.; Faita, G.; Quadrelli, P. Chem. Rev. 2003, 103,
3119e3154.
2006, 74, 635e638; (f) Itoh, T.; Uehara, H.; Ogiso, K.; Nomura, S.;
Hayase, S.; Kawatsura, M. Chem. Lett. 2007, 36, 50e51.
2. (a) Comprehensive Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A.,
Yamamoto, H., Eds.; Springer: Berlin, 1999; (b) Catalytic Asymmetric
Synthesis, 2nd ed.; Ojima, I., Ed.; Wiley-VCH: New York, NY, 2000.
3. See Refs. 1aec.
1
18. Similar results about the difference between isopropyl group and
phenyl group in ironepybox complexes were also reported by Hossain,
et al., see: Redlich, M.; Hossain, M. M. Tetrahedron Lett. 2004, 45,
8987e8990.
1
1
4. Kawatsura, M.; Komatsu, Y.; Yamamoto, M.; Hayase, S.; Itoh, T. Tetra-
hedron Lett. 2007, 48, 6480e6482.
0
0
0
˚
19. The exact role of molecular sieves 4 A is not clear in this moment.
1
5. BINAP¼(R)- or (S)-2,2 -bis(diphenylphosphino)-1,1 -binaphthyl. MOP¼
0
(
R)- or (S)-2-(diphenylphosphino)-2,2 -methoxy-1,1 -binaphthyl, and its
20. We also examined the reaction of 1g by 1 equiv of iron/pybox catalyst, but
the enantioselectivity didn’t increase.
analogues. phox¼(R)- or (S)-2-[2-(diphenylphosphino)phenyl]-4-(1-meth-
ylethyl)-4,5-di-hydrooxazole, and its analogues. pybox¼2,6-bis[(4R)- or
21. Soloshonok, V. A.; Cai, C.; Hruby, V. J.; Meervelt, L. V.; Yamazaki, T.
J. Org. Chem. 2000, 65, 6688e6696.
22. Kanazawa, Y.; Tsuchiya, Y.; Kobayashi, K.; Shiomi, T.; Itoh, J.-I.;
Kikuchi, M.; Yamamoto, Y.; Nishiyama, H. Chem.dEur. J. 2006, 12,
63e71.
(
4S)-4-(i-propyl)-2-oxazolin-2-yl]pyridine, and its analogues. box¼2,2-
bis[(4S)-4-phenyl-2-oxazolin-2-yl]propane, and its analogues. Jacobsen
0
ligand¼(1R,2R) or (1S,2S)-1,2-cycloheanediamino-N,N -bis(3,5-di-tert-
butylsalicylidene).