Enantioselective oxidation of sulfides with H2O2 catalyzed by a pre-formed manganese complex

Article abstract of DOI:10.1039/c4ra09832c

A facile and environmentally friendly method is presented for the asymmetric oxidation of sulfides with H₂O₂, utilizing a pre-formed manganese complex. Just in the presence of a low catalytic amount of carboxylic acid (CA), a variety of sulfide substrates, including aryl alkyl, aryl benzyl and cyclic sulfides, reacted to form chiral sulfoxides in high yields (up to 95%) and excellent enantioselectivities (>99% ee) under mild conditions. Moreover, the practical utility of the method has been demonstrated by the synthesis of esomeprazole and albendazole sulfoxide (ABZO).

Full text of DOI:10.1039/c4ra09832c

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Enantioselective oxidation of sulfides with H2O2
catalyzed by a pre-formed manganese complex†
Cite this: RSC Adv., 2014, 4, 46545
Wen Dai,ab Guosong Li,a Lianyue Wang,a Bo Chen,ab Sensen Shang,ab Ying Lva
a
*
and Shuang Gao
A facile and environmentally friendly method is presented for the asymmetric oxidation of sulfides with
H2O2, utilizing a pre-formed manganese complex. Just in the presence of a low catalytic amount of
carboxylic acid (CA), a variety of sulfide substrates, including aryl alkyl, aryl benzyl and cyclic sulfides,
reacted to form chiral sulfoxides in high yields (up to 95%) and excellent enantioselectivities (>99% ee)
under mild conditions. Moreover, the practical utility of the method has been demonstrated by the
synthesis of esomeprazole and albendazole sulfoxide (ABZO).
Received 5th September 2014
Accepted 19th September 2014
DOI: 10.1039/c4ra09832c
www.rsc.org/advances
porphyrin-inspired manganese complexes with H2O2, leading to
excellent enantioselectivities (Scheme 1).52 However, the excel-
Introduction
lent enantioselectivities were mainly attributed to the syner-
gistic combination of initial asymmetric sulfoxidation with the
following oxidative kinetic resolution process. So the formation
of signicant amounts of sulfone which made the separation
and purication difficult was inevitable and a large excess of
hydrogen peroxide (2.0 equiv.) was required. In addition, a high
catalyst loading (1 mol%) was required and the dichloro-
methane was employed as the solvent which is environmentally
unfriendly. With this background in mind, we wish to describe
the expansion of this early investigation resulting in improved
yields by further lowering the catalyst loading and suppressing
the sulfones formation under relatively green processes, while
retaining good enantioselectivities and further reducing the
amount of hydrogen peroxide through variation of acid addi-
tive, solvent and ligand. Herein, we report a rapid, efficient and
environmentally benign asymmetric sulfoxidation method with
H2O2 by an pre-formed manganese complex, providing a broad
range of sulfoxides in high yields with absence or very limited
amount of overoxidation to produce sulfone. The practical
utility of the method has further been underscored by the
synthesis of esomeprazole and ABZO.
Chiral sulfoxides are useful auxiliaries and ligands in modern
organic synthesis and an important class of biologically active
molecules (e.g., modanil, sulindac and esomeprazole).1–17 In
view of the importance of optically pure sulfoxides, intensive
effort has been devoted to the development of various methods
towards sulfoxides with high enantiomeric purity.6,18–21 Among
all methods developed so far, the asymmetric oxidation of cor-
responding suldes is one of the most powerful and reliable
route. Thus, the last few decades have witnessed the signicant
advances in the eld of asymmetric sulfoxidation. Since Kagan
and Modena reported the rst enantioselective titanium-
catalyzed asymmetric oxidation of suldes in 1984,22 several
other elegant metal-based catalyst systems have also been
developed.23–51 However, there are disadvantages associated
with these catalyst systems such as harsh reaction conditions,
long reaction time or toxic and expensive catalysts. In addition,
although high enantioselectivity has been achieved for certain
classes of suldes, they oen lack generality. For example,
methods for cyclic, sterically hindered or long alkyl substituted
suldes have been still rarely exploited. Consequently, nding a
general catalytic system with high conversion and selectivity
that utilizes a readily available and non-toxic catalyst and
environmentally benign oxidants remains an attractive goal.
Recently, we described a new approach to asymmetric
oxidation of suldes that involved the application of a
aDalian National Laboratory for Clean Energy, Dalian Institute of Chemical Physics,
Chinese Academy of Sciences, Dalian, 116023, People's Republic of China. E-mail:
sgao@dicp.ac.cn; Fax: +86-0411-84379248; Tel: +86-0411-84379248
bUniversity of Chinese Academy of Sciences, Beijing, 10049, People's Republic of China
† Electronic supplementary information (ESI) available: 1H and 13C NMR spectra
are available for compounds esomeprazole, ABZO, 2a–2z and 3a–3b. HPLC data
are available for esomeprazole, ABZO, 2a–2z and 3a–3b. See DOI:
10.1039/c4ra09832c
Scheme 1 Strategy for the development of asymmetric sulfoxidation.
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Table 1 Screening of the identity and amount of CA
Results and discussion
Early study has shown that CA played a key positive role in
enhancing enantioselectivities in Mn or Fe-catalyzed asym-
metric epoxidation.53–55 Because of that, an extensive study was
performed to investigate the role of CA in our catalyst system.
Initially, thioanisole (1a) was employed as the model substrate.
The reactions were conducted with 1a (1.0 equiv.), CA (1.0
equiv.), H2O2 (1.2 equiv.) and 1 mol% of catalyst which
was generated from Mn(OTf)2 and L2, in isopropanol (IPA) at
ꢀ10 ꢁC. Poor activity was observed when inorganic acid H3PO4
or sodium acetate was used (Table 1, entries 1 and 2). Then the
reaction was carried out by replacing the H3PO4 or sodium
acetate with a wide variety of aliphatic acids. Improved perfor-
mance both in terms of yields and enantioselectivities could be
gained (entries 3–12). The results indicated that both the proton
and carboxylic group were needed in the asymmetric sulfox-
idation process. Among these aliphatic acids, the adamantane
carboxylic acid (aca) provided the best result (90% yield, 80% ee;
entry 5). Perhaps the sterically hindered aca acting as an
auxiliary ligand incorporated into the active species which
could impart highly rigid environment around the active
species lead to a drastic increase in enantioselectivity.56 Unfor-
tunately, when the heterocyclic aromatic carboxylic acid nico-
tinic acid was surveyed, the conversion was relatively low (entry
13). In addition to the racemic CA, the chiral carboxylic acids S-
ibuprofen and (1S)-(ꢀ)-camphanic acid were also investigated.
Disappointedly, only moderate yields and enantioselectivities
were obtained (entries 14 and 15). Aer testing CA loading, the
amount of CA was successfully lowered to 20 mol% with no
decrease of yield and enantioselectivity (entries 16 and 17).
Further reducing the CA loading to 10% mol resulted in a lower
enantioselectivity with the yield being maintained (entry 18).
Finally, the inuence of temperature was examined. The
enantioselectivity had an obvious increase when the tempera-
Entry
Additive
Yielda (%)
eeb (%)
1
2
3
AcONa
H3PO4
CH3COOH
<5
<5
90
—
—
62
4
66
82
5
65
76
6
7
8
90
72
70
80
70
80
9
71
62
80
50
10
11
12
80
76
58
48
13
14
14
70
60
70
ꢁ
ture was decreased to ꢀ20 C (entry 19). The enantioselectivity
almost remained the same by further lowering the temperature
ꢁ
to ꢀ30 C (entry 20).
Next, we extended our search to the inuence of the solvent.
Further assessment of solvent revealed that transformation was
very sensitive to reaction medium. In the initial screening,
various single solvents were applied. The reaction occurred
smoothly in the protic polar EtOH with good yield and enan-
tioselectivity (Table 2, entry 1). When the oxidation was carried
out in aprotic solvent, only the low conversion was observed
(entries 2–6). Then, we focused on screening various mixed
solvents of DCM and aprotic solvent, affording the desired
sulfoxide in moderate yields and enantioselectivities (entries 7–
11). Gratifyingly, replacement of the mixed solvents of DCM and
aprotic solvent with DCM and protic solvent resulted in signif-
icant improvement in yields (entries 12–15). Perhaps the protic
solvent can coordinate to the manganese catalyst, thereby dis-
placing the sulfoxide, which signicantly suppresses over-
oxidation of sulfoxide.43 Among the mixed solvents of DCM
and protic solvent, the solvent of DCM and IPA with a volume
ratio of 1/2 gave the best result (entry 14). Pleasingly, replacing
15
70
48
16c
17d
18e
19f
20g
aca
aca
aca
aca
aca
91
89
89
88
86
80
81
77
87
84
a
b
c
Isolated yields. Determined by chiral HPLC analysis. aca (0.5
d
e
f
equiv.). aca (20 mol%). aca (10 mol% equiv.). aca (20 mol%),
ꢀ20 ꢁC. g aca (20 mol%), ꢀ30 ꢁC.
the mixed solvent of DCM and IPA with CH3CN and IPA resulted
in slight increase in yields with enantioselectivity being
remained (88% yield, 90% ee; entry 16).
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Table 2 Investigation of solvent
Table 3 Investigation of effect of ligand structure
Entry
Solvent
Yielda (%)
eeb (%)
1
2
3
4
5
6
7
8
EtOH
DCM
CHCl3
CCl4
Dioxane
Toluene
DCM–toluene (1 : 2)
DCM–THF (1 : 2)
DCM–AcOEt (1 : 2)
DCM–hexane (1 : 2)
DCM–cyclohexane (1 : 2)
DCM–EtOH (1 : 2)
DCM–n-BuOH (1 : 2)
DCM–IPA (1 : 2)
DCM–t-BuOH (1 : 2)
CH3CN–i-PrOH (1 : 2)
86
32
8
80
76
70
—
—
—
78
80
82
76
79
82
80
90
85
90
Entry
Ligand
% Yielda
% eeb
<5
<5
<5
69
76
74
72
64
91
92
86
90
88
1
2
3
4
5
6
7
8
L1
L3
L4
L5
L6
L7
L8
L9
L2
L2
L2
80
92
90
89
74
92
38
85
87
84
82
85
80
84
86
80
81
74
8
9
10
11
12
13
14
15
16
9c
10d
11e
91
89
89
a
Isolated yields. b Determined by chiral HPLC analysis.
a
Isolated yields. b Determined by chiral HPLC analysis. c Mn(OTf)2 (0.5
mol%), L2 (0.5 mol%). d Mn(OTf)2 (0.25 mol%), L2 (0.25 mol%). e 50%
H2O2 (1.1 equiv.).
Various ligands were then screened under the mixed solvent
CH3CN and IPA with a ratio of 1/2 to nd the optimum ligand
for our catalyst system. Replacing of ligand L2 with various
ligands containing mono-substituted oxazolines also resulted
in good yields and enantioselectivities (Table 3, entries 1–6).
However, when the ligand L8 bearing methyl-substituted oxa-
zolines was used, both yield and enantioselectivity dropped
drastically (entry 7). The result suggested that the hydropho-
bicity of catalyst imposed by ligand is crucial to maintaining the
good activity of catalyst. It is speculated that hydrophobic
structure of ligands allows the substrate to approach the active
center of catalysts more easily and reduces the decomposition
of hydrogen peroxide.56 Then ligand L9, with bis-substituted
oxazolines, was also been examined. Unfortunately, only a low
enantioselectivity was obtained, albeit with good yield (entry 8).
Taking all of our ndings into consideration, ligand L2 was
identied as the ligand providing the best yield and enantio-
selectivity. Remarkably, the catalyst loading was successfully
lowered to 0.5 mol% without erosion of yield and enantiose-
lectivity, and even a catalyst loading of 0.25 mol% gave a good
result (entries 9–10). Finally, the loading of H2O2 was investi-
gated. We found that 1.2 equiv. of H2O2 was necessary in order
to achieve the best result (entry 11).
preserved even when extending the alkyl chain linearly from C1
(methyl) to C5 (pentyl) (entries 13–20). It is noteworthy that
condensed aromatic substrate 2-(methylthio)naphthalene and
2-(phenylthio)ethanol could also be oxidized in good yields with
excellent enantioselectivities (entries 11 and 12). Encouraged by
these results, we turned our attention to the sterically hindered
aryl benzyl suldes. Gratifyingly, high yields and excellent
enantioselectivities could be achieved (entries 21–27). In order
to extend the substrate scope further, we expected that the cyclic
suldes would be oxidized. Fortunately, the present oxidation
could also be successfully applied to cyclic suldes, giving the
corresponding sulfoxides in high yields with excellent enan-
tioselectivities (entries 28 and 29).
On the basis of our previous work,52 a possible mechanism is
proposed (Scheme 2). Although the CA additive used in the
current catalyst system differs from our previous work, the
reaction mechanism should be the same. At the initial stage, the
starting Mn(II) complex is converted to the Mn(III) intermediate
3. Then the active species Mn(V)–oxo complex 4 is formed via
synergistic cooperation of ligands and CA in promoting O–O
cleavage in the intermediate 3. The formed Mn(V)–oxo complex
directly oxidizes the suldes to the corresponding sulfoxides
along with the formation of Mn(III) intermediate 3.
With the optimized conditions in hand, the asymmetric
oxidation of a series of representative suldes was examined
(Table 4). A broad range of aryl methyl suldes were smoothly
converted to the corresponding sulfoxides in high yields with
excellent enantioselectivities within short times regardless of
the electronic properties and position of the substituent on the
aromatic ring (entries 1–10). Good yields and excellent were
The successful results of asymmetric oxidation of suldes
prompted us to further explore the oxidative kinetic resolution
of racemic sulfoxides. As outlined in Scheme 3, we performed
the experiments under the optimized conditions using racemic
methyl phenyl sulfoxide 2a and benzyl phenyl sulfoxide 2x and
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Table 4 Substrate scope of asymmetric sulfoxidation
Table 4 (Contd.)
% Yielda
88
% eeb
95
Entry
1
Product
% Yielda
88
% eeb
90
Entry
17c
Product
R ¼ n-pentyl (2p)
2
3
94
90
95
90
18
R ¼ Et (2q)
95
92
90
94
91
91
19c
20c
R ¼ n-Bu (2r)
R ¼ n-pentyl (2s)
21
22
90
90
98
99
4
5
90
93
90
94
23
91
92
6
92
94
24
25
90
95
98
7
91
92
90
95
90
95
90
80
>99
8
26
27
28
93
94
76
93
>99
92
9
10
11
12
88
89
87
95
29
91
94
a
Isolated yields. b Determined by chiral HPLC analysis. c 50% H2O2 (1.3
equiv.).
13
92
97
found that the oxidation of (S)-enantiomer was obviously pref-
erential to (R)-enantiomer with a relative ratio of 7.7 and 11.0,
respectively.
To further evaluate the practical utility, the asymmetric sul-
foxidation was enlarged to a gram scale under the optimized
conditions, and the desired product 2b was furnished with 95%
yield and 91% ee (Scheme 4).
14
15
16c
R ¼ Et (2n)
92
93
87
92
84
95
R ¼ n-Bu (2o)
R ¼ n-Bu (2o)
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in 76% yield with up to 87% ee. Furthermore, the synthesis of
ABZO was also been achieved. The ABZO is the pharmacologi-
cally active ingredient of albendazole (ABZ) which is a broad-
spectrum benzimidazole anthelmintic drug widely used in
human and veterinary medicine.58,59 The asymmetric oxidation
of ABZ was carried out in mixed solvent of CH3CN, IPA and
acetic acid with a ratio 1/2/2 because of the solubility of
substrate, providing the ABZO in 48% yield and 97% ee
(Scheme 5).
Conclusions
Scheme 2 A proposed catalytic cycle.
In summary, we have developed a highly enantioselective
asymmetric oxidation of a variety of suldes by a low loading
(0.5 mol%) of inexpensive and readily available pre-formed
manganese complex with H2O2. The optically active sulfoxides
were obtained in high yields (up to 95%) with excellent enan-
tioselectivities (>99% ee). The practical application utility of the
current system has further been demonstrated by the synthesis
of esomeprazole and ABZO. Furthermore, the new methodology
was successfully applied to the oxidative kinetic resolution of
racemic sulfoxides, providing an alternative approach for the
synthesis of optically active sulfoxides. Extension of the strategy
to other reactions is ongoing in our laboratory.
Experimental section
General information
Scheme 3 Oxidative kinetic resolution of racemic 2a and 2x.
Unless otherwise stated, all reactions and manipulations were
carried out under argon atmosphere using standard Schlenk
techniques or in an argon-lled glove-box. All chemicals were
obtained from commercial sources and were used without
further purication. Solvents were treated prior to use accord-
ing to the standard methods. Column chromatography was
carried out on silica gel (300–400 mesh) using a forced ow of
eluent at 0.3–0.5 bar pressure. NMR Spectra were recorded at
room temperature in CDCl3 or DMSO on 400 MHz spectrome-
ters. The chemical shis for 1H NMR were recorded in ppm
downeld from tetramethylsilane (TMS) as the internal stan-
dard. The chemical shis for 13C NMR were recorded in ppm
downeld using the central peak of CDCl3 (77.16 ppm) or DMSO
(40.58 ppm) as the internal standard. 13C NMR was broad-band
decoupled from hydrogen nuclei. Coupling constants (J) are
reported in hertz and refer to apparent peak multiplications.
Scheme 4 Gram-scale synthesis of sulfoxide 2b.
To broaden the application of our methodology, we rst
focused on the development of a facile route to esomeprazole,
which is chiral proton pump inhibitor for the treatment of
gastroesophageal reux disease.9,57 Compound 3a which is the
key intermediate for the synthesis of the esomeprazole was
treated under the current system, affording the desired product
Representative procedures for the asymmetric sulfoxidation56
A solution of Mn(OTf)2 (0.0084 M solution in CH3CN, 0.25 mL,
0.0021 mmol) was added to L2 (0.0084 M solution in CH3CN,
0.25 mL, 0.0021 mmol) at room temperature. The reaction
mixture was stirred at room temperature for 6 h. To the solution
of manganese complex was directly added substrate (0.42
mmol), adamantane carboxylic acid (15 mg, 0.084 mmol) and
ꢁ
isopropanol (1 mL). Then decrease the temperature to ꢀ20 C,
50% H2O2 (34.3 mg, 0.51 mmol) was rapidly added and the
mixture was stirred at ꢀ20 ꢁC for 2.0 h. At this point, a saturated
aqueous solution of NaHCO3 (8 mL) was added and the
Scheme 5 Synthesis of esomeprazole and ABZO.
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resulting mixture was extracted with EtOAc (10 mL ꢂ 3). Then, 2.68 (s, 3H); 13C {1H} NMR (100 MHz, CDCl3) d 145.5, 133.1,
the organic layer was combined and washed with brine, dried 126.0, 125.7, 44.6; MS (EI) m/z 220.0 (M+); HPLC (DAICEL OB-H,
over MgSO4 and concentrated at reduced pressure. The residue hexane–isopropanol 70 : 30, ow rate: 0.5 mL minꢀ1, 220 nm): tr
was puried by silica gel column chromatography to afford the (minor) ¼ 14.5 min, tr (major) ¼ 18.7 min.
corresponding sulfoxide.
(R)-1-Fluoro-2-(methylsulnyl)benzene (2h).10 Yellow oil,
(R)-(Methylsulnyl)benzene (2a).52 Colorless oil, puried by puried by column chromatography on silica gel (20% EtOAc in
1
column chromatography on silica gel (20% EtOAc in petroleum petroleum ether) (61.1 mg, 92% yield, 95% ee). H NMR (400
ether) (52.0 mg, 88% yield, 90% ee). HPLC (DAICEL OD-H, MHz, CDCl3) d 7.87 (m, 1H), 7.50 (m, 1H), 7.40 (m, 1H), 7.18–
hexane–isopropanol 70 : 30, ow rate: 0.5 mL minꢀ1, 220 nm): 7.08 (m, 1H), 2.84 (s, 3H); 13C {1H} NMR (100 MHz, CDCl3) d
tr (major) ¼ 11.1 min, tr (minor) ¼ 13.5 min.
157.5 (d, J ¼ 247.5 Hz), 132.7, 132.6, 125.4, 115.8, 115.6, 42.1; MS
(R)-1-Chloro-2-(methylsulnyl)benzene (2b).52 Colorless oil, (EI) m/z 158.0 (M+); HPLC (DAICEL OB-H, hexane–isopropanol
puried by column chromatography on silica gel (20% EtOAc in 70 : 30, ow rate: 0.5 mL minꢀ1, 220 nm): tr (minor) ¼ 11.7 min,
1
petroleum ether) (68.9 mg, 94% yield, 95% ee). H NMR (400 tr (major) ¼ 19.2 min.
MHz, CDCl3) d 7.92 (d, J ¼ 7.7 Hz, 1H), 7.50 (m, 1H), 7.41 (m,
(R)-1-Methoxy-2-(methylsulnyl)benzene (2i).60 Colorless oil,
1H), 7.36 (d, J ¼ 7.7 Hz, 1H), 2.79 (s, 3H); 13C {1H} NMR (100 puried by column chromatography on silica gel (50% EtOAc in
1
MHz, CDCl3) d 144.4, 132.5, 130.3, 128.7, 125.9, 42.2; MS (EI) m/z petroleum ether) (64.3 mg, 90% yield, 90% ee). H NMR (400
174.0 (M+); HPLC (DAICEL OD-H, hexane–isopropanol 90 : 10, MHz, CDCl3) d 7.82 (dd, J ¼ 7.7, 1.7 Hz, 1H), 7.55–7.37 (m, 1H),
ow rate: 0.5 mL minꢀ1, 220 nm): tr (major) ¼ 19.4 min, tr 7.19 (m, 1H), 6.93 (d, J ¼ 8.2 Hz, 1H), 3.89 (s, 3H), 2.77 (s, 3H);
(minor) ¼ 20.7 min.
13C {1H} NMR (100 MHz, CDCl3) d 154.8, 133.2, 131.9, 124.6,
(R)-1-Chloro-3-(methylsulnyl)benzene (2c).52 Colorless oil, 121.7, 110.6, 55.7, 41.2; MS (EI) m/z 170.1 (M+); HPLC (DAICEL
puried by column chromatography on silica gel (20% EtOAc in OD-H, hexane–isopropanol 90 : 10, ow rate: 0.5 mL minꢀ1, 254
1
petroleum ether) (66.0 mg, 90% yield, 98% ee). H NMR (400 nm): tr (minor) ¼ 25.8 min, tr (major) ¼ 29.0 min.
MHz, CDCl3) d 7.64 (s, 1H), 7.46 (m, 3H), 2.72 (s, 3H); 13C {1H}
(R)-Methyl-2-(methylsulnyl)benzoate (2j).60 Colorless oil,
NMR (100 MHz, CDCl3) d 148.5, 136.3, 131.8, 131.2, 124.2, 122.2, puried by column chromatography on silica gel (20% EtOAc in
1
44.6; MS (EI) m/z 174.0 (M+); HPLC (DAICEL OD-H, hexane– petroleum ether) (79.1 mg, 95% yield, 80% ee). H NMR (400
isopropanol 95 : 5, ow rate: 0.5 mL minꢀ1, 220 nm): tr (major) MHz, CDCl3) d 8.27 (d, J ¼ 7.9 Hz, 1H), 8.05 (d, J ¼ 7.7 Hz, 1H),
¼ 37.6 min, tr (minor) ¼ 40.6 min.
7.85–7.71 (m, 1H), 7.54 (m, 1H), 3.91 (s, 3H), 2.81 (s, 3H); 13C
(R)-1-Chloro-4-(methylsulnyl)benzene (2d).52 Colorless oil, {1H} NMR (100 MHz, CDCl3) d 166.30, 151.0, 134.7, 131.3, 130.8,
puried by column chromatography on silica gel (20% EtOAc in 127.0, 124.7, 53.2, 44.6; MS (EI) m/z 198.0 (M+); HPLC (DAICEL
petroleum ether) (66.0 mg, 90% yield, 90% ee). H NMR (400 OD-H, hexane–isopropanol 90 : 10, ow rate: 0.5 mL minꢀ1, 254
1
MHz, CDCl3) d 7.56 (d, J ¼ 8.5 Hz, 2H), 7.47 (d, J ¼ 8.5 Hz, 2H), nm): tr (minor) ¼ 25.8 min, tr (major) ¼ 29.0 min.
2.68 (s, 3H); 13C {1H} NMR (100 MHz, CDCl3) d 144.9, 137.8,
(R)-2-(Phenylsulnyl)ethanol (2k).61 Colorless oil, puried by
130.2, 125.5, 44.6; MS (EI) m/z 174.0 (M+); HPLC (DAICEL OB-H, column chromatography on silica gel (20% EtOAc in petroleum
hexane–isopropanol 70 : 30, ow rate: 0.5 mL minꢀ1, 220 nm): tr ether) (62.9 mg, 88% yield, 87% ee). 1H NMR (400 MHz, CDCl3) d
(minor) ¼ 13.2 min, tr (major) ¼ 18.4 min.
7.60 (m, 2H), 7.47 (m, 3H), 4.34 (s, 1H), 4.10 (m, 1H), 3.96–3.84
(R)-1-Bromo-2-(methylsulnyl)benzene (2e).52 Colorless oil, (m, 1H), 3.05 (m, 1H), 2.96–2.86 (m, 1H); 13C {1H} NMR (100
puried by column chromatography on silica gel (20% EtOAc in MHz, CDCl3) d 143.6, 131.8, 130.0, 124.6, 60.1, 56.8; MS (EI) m/z
petroleum ether) (85.6 mg, 93% yield, 94% ee). H NMR (400 170.2 (M+); HPLC (DAICEL OD-H, hexane–isopropanol 70 : 30,
1
MHz, CDCl3) d 7.93 (dd, J ¼ 7.8, 1.3 Hz, 1H), 7.63–7.51 (m, 2H), ow rate: 0.5 mL minꢀ1, 220 nm): tr (major) ¼ 10.0 min, tr
7.35 (dd, J ¼ 7.8, 1.3 Hz, 1H), 2.80 (s, 3H); 13C {1H} NMR (100 (minor) ¼ 11.1 min.
MHz, CDCl3) d 133.5, 132.8, 129.3, 126.3, 119.0, 42.5; MS (EI) m/z
(R)-2-(Methylsulnyl)naphthalene (2l).6 White solid, puried
220.0 (M+); HPLC (DAICEL OD-H, hexane–isopropanol 90 : 10, by column chromatography on silica gel (50% EtOAc in petro-
ow rate: 0.5 mL minꢀ1, 220 nm): tr (major) ¼ 20.8 min, tr leum ether) (71.1 mg, 89% yield, 95% ee). H NMR (400 MHz,
1
(minor) ¼ 22.8 min.
CDCl3) d 8.22 (s, 1H), 7.99 (d, J ¼ 8.6 Hz, 1H), 7.93 (m, 2H), 7.60
(R)-1-Bromo-3-(methylsulnyl)benzene (2f).52 Colorless oil, (m, 3H), 2.79 (s, 3H); 13C {1H} NMR (100 MHz, CDCl3) d 142.9,
puried by column chromatography on silica gel (20% EtOAc in 134.5, 133.0, 129.6, 128.5, 128.1, 127.8, 127.4, 124.1, 119.5, 43.8;
petroleum ether) (84.6 mg, 92% yield, 94% ee). H NMR (400 MS (EI) m/z 190.0 (M+); HPLC (DAICEL OD-H, hexane–iso-
1
MHz, CDCl3) d 7.78 (s, 1H), 7.60 (d, J ¼ 7.8 Hz, 1H), 7.52 (d, J ¼ propanol 70 : 30, ow rate: 0.5 mL minꢀ1, 220 nm): tr (major) ¼
7.8 Hz, 1H), 7.37 (m, 1H), 2.71 (s, 3H); 13C {1H} NMR (100 MHz, 15.1 min, tr (minor) ¼ 17.2 min.
CDCl3) d 134.7, 131.4, 127.1, 124.2, 122.7, 44.6; MS (EI) m/z 220.0
(R)-1-Chloro-3-(ethylsulnyl)benzene (2m).62 Colorless oil,
(M+); HPLC (DAICEL OD-H, hexane–isopropanol 90 : 10, ow puried by column chromatography on silica gel (20% EtOAc in
rate: 0.5 mL minꢀ1, 220 nm): tr (major) ¼ 25.0 min, tr (minor) ¼ petroleum ether) (73.0 mg, 92% yield, 97% ee). H NMR (400
1
1
26.9 min.
MHz, CDCl3) H NMR (400 MHz, CDCl3) d 7.62 (d, J ¼ 0.9 Hz,
(R)-1-Bromo-4-(methylsulnyl)benzene (2g).52 Colorless oil, 1H), 7.46 (m, 3H), 2.93 (m, 1H), 2.83–2.66 (m, 1H), 1.22 (t, J ¼ 7.4
puried by column chromatography on silica gel (20% EtOAc in Hz, 3H); 13C {1H} NMR (100 MHz, CDCl3) d 145.6, 135.6, 131.1,
petroleum ether) (83.7 mg, 91% yield, 90% ee). H NMR (400 130.3, 124.3, 122.3, 50.3, 5.8; MS (EI) m/z 188.0 (M+); HPLC
1
MHz, CDCl3) d 7.63 (d, J ¼ 8.4 Hz, 2H), 7.49 (d, J ¼ 8.4 Hz, 2H),
46550 | RSC Adv., 2014, 4, 46545–46554
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(DAICEL OB-H, hexane–isopropanol 70 : 30, ow rate: 0.5 mL 7.36 (m, 1H), 3.09 (m, 1H), 2.84–2.65 (m, 1H), 1.91 (m, 1H), 1.74–
minꢀ1, 220 nm): tr (minor) ¼ 11.7 min, tr (major) ¼ 15.5 min.
1.60 (m, 1H), 1.54–1.30 (m, 4H), 0.90 (t, J ¼ 7.1 Hz, 3H); 13C {1H}
(R)-1-Chloro-2-(ethylsulnyl)benzene (2n).62 Colorless oil, NMR (100 MHz, CDCl3) d 143.8, 132.9, 132.1, 128.4, 126.6, 118.7,
puried by column chromatography on silica gel (20% EtOAc in 54.8, 30.6, 22.3, 22.0, 13.8; HRMS (ESI-TOF) m/z calcd for
1
petroleum ether) (73.0 mg, 92% yield, 92% ee). H NMR (400
C
11H16BrOS [M + H]+ 277.0085, found 277.0080; HPLC (DAICEL
MHz, CDCl3) d 7.88 (dd, J ¼ 7.7, 1.6 Hz, 1H), 7.51 (m, 1H), 7.42 OB-H, hexane–isopropanol 70 : 30, ow rate: 0.5 mL minꢀ1, 220
(m, 2H), 3.13 (m, 1H), 2.86 (m, 1H), 1.25 (t, J ¼ 7.4 Hz, 3H); 13
C
nm): tr (minor) ¼ 9.4 min, tr (major) ¼ 15.4 min.
{1H} NMR (100 MHz, CDCl3) d 141.0, 131.9, 130.1, 130.0, 127.7,
(R)-(Benzylsulnyl)benzene (2t).43,52 White solid, puried by
126.6, 47.1, 5.7; MS (EI) m/z 188.0 (M+); HPLC (DAICEL OD-H, column chromatography on silica gel (20% EtOAc in petroleum
hexane–isopropanol 90 : 10, ow rate: 0.5 mL minꢀ1, 220 nm): ether) (81.8 mg, 90% yield, 98% ee). 1H NMR (400 MHz, CDCl3) d
tr (major) ¼ 15.1 min, tr (minor) ¼ 16.0 min.
7.44–7.35 (m, 4H), 7.29–7.22 (m, 4H), 7.01–6.91 (m, 2H), 4.08 (d,
(R)-1-(Butylsulnyl)-2-chlorobenzene (2o).62 Colorless oil, J ¼ 12.6 Hz, 1H), 3.98 (d, J ¼ 12.6 Hz, 1H); 13C {1H} NMR (100
puried by column chromatography on silica gel (20% EtOAc in MHz, CDCl3) d 131.7, 130.9, 129.4, 129.0, 128.8, 125.0, 64.2;
petroleum ether) (79.2 mg, 87% yield, 95% ee). H NMR (400 HRMS (ESI-TOF) m/z calcd for C13H13OS [M + H]+ 217.0687,
1
MHz, CDCl3) d 7.90 (dd, J ¼ 7.8, 1.6 Hz, 1H), 7.51 (m, 1H), 7.41 found 217.0684; HPLC (DAICEL OD-H, hexane–isopropanol
(m, 2H), 3.08 (m, 1H), 2.78 (m, 1H), 1.94–1.84 (m, 1H), 1.68–1.33 90 : 10, ow rate: 1.0 mL minꢀ1, 220 nm): tr (major) ¼ 14.1 min,
(m, 3H), 0.94 (t, J ¼ 7.3 Hz, 3H); 13C {1H} NMR (100 MHz, CDCl3) tr (minor) ¼ 17.6 min.
d 142.0, 131.8, 130.0, 129.7, 127.8, 126.2, 54.2, 24.1, 21.8, 13.6;
(R)-1-(Benzylsulnyl)-2-methylbenzene (2u).43,52 White solid,
HRMS (ESI-TOF) m/z calcd for C10H14ClOS [M + H]+ 217.0454, puried by column chromatography on silica gel (20% EtOAc in
1
found 217.0455; HPLC (DAICEL OB-H, hexane–isopropanol petroleum ether) (87.1 mg, 90% yield, 99% ee). H NMR (400
70 : 30, ow rate: 0.5 mL minꢀ1, 220 nm): tr (minor) ¼ 9.2 min, tr MHz, CDCl3) d 7.70 (m, 1H), 7.33 (m, 2H), 7.25 (d, J ¼ 7.8, 1H),
(major) ¼ 15.0 min.
7.23 (d, J ¼ 7.8, 1H), 7.20 (m, 1H), 7.15–7.05 (m, 1H), 6.96 (m,
(R)-1-Chloro-2-(pentylsulnyl)benzene (2p).62 Colorless oil, 2H), 4.07 (d, J ¼ 12.5 Hz, 1H), 3.98 (d, J ¼ 12.5 Hz, 1H), 2.05 (s,
puried by column chromatography on silica gel (20% EtOAc in 3H); 13C {1H} NMR (100 MHz, CDCl3) d 136.1, 131.5, 130.9,
1
petroleum ether) (85.3 mg, 88% yield, 95% ee). H NMR (400 130.7, 129.0, 128.8, 127.7, 124.8, 62.9, 18.6; HRMS (ESI-TOF) m/z
MHz, CDCl3) d 7.90 (dd, J ¼ 7.7, 1.6 Hz, 1H), 7.51 (m, 1H), 7.41 calcd for C14H15OS [M + H]+ 231.0844, found 231.0844; HPLC
(m, 2H), 3.07 (m, 1H), 2.77 (m, 1H), 1.93–1.82 (m, 1H), 1.71–1.58 (DAICEL OD-H, hexane–isopropanol 90 : 10, ow rate: 1.0 mL
(m, 1H), 1.54–1.29 (m, 4H), 0.89 (t, J ¼ 7.1 Hz, 3H); 13C {1H} NMR minꢀ1, 220 nm): tr (major) ¼ 13.2 min, tr (minor) ¼ 16.7 min.
(100 MHz, CDCl3) d 142.0, 131.8, 130.0, 129.7, 127.8, 126.1, 54.5,
(R)-1-(Benzylsulnyl)-3-methylbenzene (2v).43,52 White solid,
30.6, 22.2, 21.8, 13.8; HRMS (ESI-TOF) m/z calcd for C11H16ClOS puried by column chromatography on silica gel (20% EtOAc in
1
[M + H]+ 231.0610, found 231.0626; HPLC (DAICEL OB-H, petroleum ether) (88.0 mg, 91% yield, 92% ee). H NMR (400
hexane–isopropanol 85 : 15, ow rate: 0.5 mL minꢀ1, 220 nm): MHz, CDCl3) d 7.32–7.20 (m, 5H), 7.20–7.11 (m, 2H), 6.98 (dd, J
tr (minor) ¼ 9.7 min, tr (major) ¼ 21.9 min.
¼ 7.7, 1.4 Hz, 2H), 4.06 (d, J ¼ 12.6 Hz, 1H), 3.95 (d, J ¼ 12.6 Hz,
(R)-1-Bromo-2-(ethylsulnyl)benzene (2q).62 Colorless oil, 1H), 2.32 (s, 3H); 13C {1H} NMR (100 MHz, CDCl3) d 139.6, 132.5,
puried by column chromatography on silica gel (20% EtOAc in 131.0, 129.2, 129.0, 128.8, 125.3, 122.1, 64.3, 21.9; HRMS (ESI-
petroleum ether) (93.0 mg, 95% yield, 94% ee). H NMR (400 TOF) m/z calcd for C14H15OS [M + H]+ 231.0847, found
1
MHz, CDCl3) d 7.86 (dd, J ¼ 8.0, 1.6 Hz, 1H), 7.56 (m, 2H), 7.36 231.0844; HPLC (DAICEL OD-H, hexane–isopropanol 90 : 10,
(m, 1H), 3.13 (m, 1H), 2.85 (m, 1H), 1.26 (t, J ¼ 7.4 Hz, 3H); 13
C
ow rate: 1.0 mL minꢀ1, 220 nm): tr (major) ¼ 12.3 min, tr
{1H} NMR (100 MHz, CDCl3) d 142.9, 133.0, 132.1, 128.2, 127.0, (minor) ¼ 15.4 min.
118.8, 47.4, 5.8; MS (EI) m/z 233.9 (M+); HPLC (DAICEL OD-H,
(R)-1-(Benzylsulnyl)-4-methylbenzene (2w).43,52 White solid,
hexane–isopropanol 90 : 10, ow rate: 0.5 mL minꢀ1, 220 nm): puried by column chromatography on silica gel (20% EtOAc in
1
tr (major) ¼ 15.2 min, tr (minor) ¼ 17.3 min.
petroleum ether) (87.1 mg, 90% yield, 98% ee). H NMR (400
(R)-1-Bromo-2-(butylsulnyl)benzene (2r).62 Colorless oil, MHz, CDCl3) d 7.24 (m, 5H), 7.22 (d, J ¼ 7.6 Hz, 2H), 6.98 (d, J ¼
puried by column chromatography on silica gel (20% EtOAc in 7.6 Hz, 2H), 4.08 (d, J ¼ 12.5 Hz, 1H), 3.95 (d, J ¼ 12.5 Hz, 1H),
1
petroleum ether) (104.0 mg, 90% yield, 91% ee). H NMR (400 2.38 (s, 3H); 13C {1H} NMR (100 MHz, CDCl3) d 130.9, 130.1,
MHz, CDCl3) d 7.89 (dd, J ¼ 8.0, 1.6 Hz, 1H), 7.56 (m, 2H), 7.36 129.2, 129.0, 128.8, 125.1, 64.3, 22.0; HRMS (ESI-TOF) m/z calcd
(m, 1H), 3.10 (m, 1H), 2.76 (m, 1H), 1.90 (m, 1H), 1.69–1.57 (m, for C14H15OS [M + H]+ 231.0847, found 231.0844; HPLC (DAI-
1H), 1.56–1.39 (m, 2H), 0.95 (t, J ¼ 7.3 Hz, 3H); 13C {1H} NMR CEL OD-H, hexane–isopropanol 90 : 10, ow rate: 1.0 mL
(100 MHz, CDCl3) d 143.8, 132.9, 132.1, 128.4, 126.6, 118.7, 54.6, minꢀ1, 220 nm): tr (major) ¼ 13.5 min, tr (minor) ¼ 16.4 min.
24.2, 21.8, 13.7; HRMS (ESI-TOF) m/z calcd for C10H14BrOS [M +
(R)-1-(Benzylsulnyl)-2-chlorobenzene (2x).48 White solid,
H]+ 260.9949, found 260.9941; HPLC (DAICEL OB-H, hexane– puried by column chromatography on silica gel (20% EtOAc in
isopropanol 70 : 30, ow rate: 0.5 mL minꢀ1, 220 nm): tr (minor) petroleum ether) (100.0 mg, 95% yield, >99% ee). 1H NMR (400
1
¼ 8.8 min, tr (major) ¼ 15.7 min.
MHz, CDCl3) H NMR (400 MHz, CDCl3) d 7.48–7.43 (m, 1H),
(R)-1-Bromo-2-(pentylsulnyl)benzene (2s).62 Colorless oil, 7.38 (m, 2H), 7.32 (m, 1H), 7.28–7.22 (m, 3H), 7.05 (dd, J ¼ 7.7,
puried by column chromatography on silica gel (20% EtOAc in 1.2 Hz, 2H), 4.29 (d, J ¼ 13.1 Hz, 1H), 4.03 (d, J ¼ 13.1 Hz, 1H);
1
petroleum ether) (100.9 mg, 92% yield, 91% ee). H NMR (400 13C {1H} NMR (100 MHz, CDCl3) d 140.8, 131.9, 130.4, 130.1,
MHz, CDCl3) d 7.89 (dd, J ¼ 8.0, 1.6 Hz, 1H), 7.66–7.47 (m, 2H), 129.4, 129.3, 128.3, 127.6, 126.8, 59.7; HRMS (ESI-TOF) m/z
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calcd for C13H12ClOS [M + H]+ 251.0297, found 251.0293; HPLC NaHCO3 (15 mL) and extracted with EtOAc (15 mL ꢂ 4). The
(DAICEL OB-H, hexane–isopropanol 90 : 10, ow rate: 1.0 mL organic layer was separated and washed with brine, dried over
minꢀ1, 220 nm): tr (minor) ¼ 10.4 min, tr (major) ¼ 13.2 min.
MgSO4 and concentrated at reduced pressure. The residue was
(R)-1-(Benzylsulnyl)-3-chlorobenzene (2y).48 White solid, puried by silica gel column chromatography to afford the 2b
puried by column chromatography on silica gel (20% EtOAc in (1.04 g, 95% yield, 91% ee).
1
petroleum ether) (98.0 mg, 93% yield, 93% ee). H NMR (400
MHz, CDCl3) d 7.45–7.40 (m, 1H), 7.37–7.25 (m, 5H), 7.20 (d, J ¼
Experimental procedure for the synthesis of esomeprazole56
7.7 Hz, 1H), 7.04–6.92 (m, 2H), 4.10 (d, J ¼ 12.6 Hz, 1H), 4.00 (d,
J ¼ 12.6 Hz, 1H); 13C {1H} NMR (100 MHz, CDCl3) d 145.0, 135.3, A solution of Mn(OTf)2 (0.0084 M solution in CH3CN, 0.25 mL,
131.3, 130.4, 130.0, 128.7, 128.6, 128.5, 124.5, 122.5, 63.6; HRMS 0.0021 mmol) was added to L2 (0.0084 M solution in CH3CN,
(ESI-TOF) m/z calcd for C13H12ClOS [M + H]+ 251.0297, found 0.25 mL, 0.0021 mmol) at room temperature. The reaction
251.0299; HPLC (DAICEL OD-H, hexane–isopropanol 95 : 5, mixture was stirred at room temperature for 6 h. To the solution
ow rate: 0.7 mL minꢀ1, 220 nm): tr (major) ¼ 37.0 min, tr of manganese complex was directly added 3a (138 mg, 0.42
(minor) ¼ 39.4 min.
mmol), adamantane carboxylic acid (37.5 mg, 0.21 mmol) and
(R)-1-(Benzylsulnyl)-2-bromobenzene (2z).48 White solid, isopropanol (1 mL). Then decrease the temperature to ꢀ20 C,
puried by column chromatography on silica gel (20% EtOAc in 50% H2O2 (91.1 mg, 1.34 mmol) was rapidly added and the
petroleum ether) (116.5 mg, 94% yield, >99% ee). 1H NMR (400 mixture was stirred at ꢀ20 ꢁC for 2.0 h. At this point, a saturated
MHz, CDCl3) d 7.56 (dd, J ¼ 7.7, 1.1 Hz, 1H), 7.43 (dd, J ¼ 7.7, 1.9 aqueous solution of NaHCO3 (4 mL) was added and the
Hz, 1H), 7.40–7.21 (m, 5H), 7.07 (m, 2H), 4.30 (d, J ¼ 13.1 Hz, resulting mixture was extracted with EtOAc (10 mL ꢂ 3). Then,
1H), 4.04 (d, J ¼ 13.1 Hz, 1H); 13C {1H} NMR (100 MHz, CDCl3) d the organic layer was combined and washed with brine, dried
142.5, 132.6, 132.2, 130.4, 129.4, 128.9, 128.8, 128.1, 127.2, over MgSO4 and concentrated at reduced pressure. The residue
118.8, 59.9; HRMS (ESI-TOF) m/z calcd for C13H12BrOS [M + H]+ was puried by silica gel column chromatography to afford the
296.9772, found 296.9774; HPLC (DAICEL OB-H, hexane–iso- esomeprazole (110 mg, 76% yield, 87% ee). 1H NMR (400 MHz,
propanol 90 : 10, ow rate: 1.0 mL minꢀ1, 220 nm): tr ¼ 14.9 CDCl3) d 12.45 (s, 1H), 8.17 (s, 1H), 7.58 (s, 1H), 6.88 (dt, J ¼ 23.3,
ꢁ
min.
11.7 Hz, 2H), 4.83–4.65 (m, 2H), 3.80 (s, 3H), 3.56 (s, 3H), 2.18 (s,
(R)-6-Chlorothiochroman-4-one-1-oxide (3a).63 White solid, 3H), 2.08 (s, 3H); 13C {1H} NMR (100 MHz, CDCl3) d 164.9, 150.2,
puried by column chromatography on silica gel (50% EtOAc in 149.3, 127.5, 126.9, 61.2, 60.4, 56.3, 13.9, 12.0; HRMS (ESI-TOF)
petroleum ether) (68.5 mg, 76% yield, 92% ee). H NMR (400 m/z calcd for C17H20N3O3S [M + H]+ 346.1225, found 346.1231;
1
MHz, CDCl3) d 8.07 (d, J ¼ 2.2 Hz, 1H), 7.77 (d, J ¼ 8.3 Hz, 1H), HPLC (DAICEL OD-H, hexane–isopropanol 80 : 20, ow rate:
7.67 (dd, J ¼ 8.3, 2.2 Hz, 1H), 3.46–3.39 (m, 3H), 2.92–2.81 (m, 1.0 mL minꢀ1, 220 nm): tr (minor) ¼ 10.9 min, tr (major) ¼
1H); 13C {1H} NMR (101 MHz, CDCl3) d 190.9, 143.9, 139.1, 13.4 min.
134.5, 130.5, 130.2, 129.0, 46.8, 30.3; HRMS (ESI-TOF) m/z calcd
for C9H8ClO2S [M + H]+ 214.9934, found 214.9935; HPLC (DAI-
Experimental procedure for the synthesis of ABZO56
CEL AD-H, hexane–isopropanol 90 : 10, ow rate: 1.0 mL minꢀ1
220 nm): tr (major) ¼ 30.2 min, tr (minor) ¼ 31.3 min.
,
A solution of Mn(OTf)2 (0.0084 M solution in CH3CN, 0.25 mL,
(R)-Dibenzo[b,e]thiepin-11(6H)-one-5-oxide (3b).63 White 0.0021 mmol) was added to L2 (0.0084 M solution in CH3CN,
solid, puried by column chromatography on silica gel (20% 0.25 mL, 0.0021 mmol) at room temperature. The reaction
EtOAc in petroleum ether) (92.6 mg, 91% yield, 94% ee). 1H mixture was stirred at room temperature for 6 h. To the solution
NMR (400 MHz, CDCl3) d 8.27–8.11 (m, 2H), 8.03 (m, 1H), 7.78 of manganese complex was directly added ABZ (111.4 mg, 0.42
(m, 1H), 7.62 (m, 2H), 7.49 (m, 1H), 7.40 (d, J ¼ 7.5 Hz, 1H), 4.85 mmol, dissolved with 1.0 mL CH3COOH) and isopropanol (1
(d, J ¼ 13.6 Hz, 1H), 4.29 (d, J ¼ 13.6 Hz, 1H); 13C {1H} NMR (100 mL). Then decrease the temperature to ꢀ20 ꢁC, 50% H2O2 (42.8
MHz, CDCl3) d 190.3, 147.0, 138.1, 134.1, 133.4, 132.5, 132.0, mg, 0.63 mmol) was rapidly added and the mixture was stirred
131.4, 130.8, 129.1, 128.0, 124.3, 61.1; HRMS (ESI-TOF) m/z at ꢀ20 ꢁC for 2.0 h. At this point, a saturated aqueous solution
calcd for C14H11O2S [M + H]+ 243.0480, found 243.0483; HPLC of NaHCO3 (10 mL) was added and the resulting mixture was
(DAICEL OD-H, hexane–isopropanol 80 : 20, ow rate: 1.0 mL extracted with EtOAc (5 mL ꢂ 6). Then, the organic layer was
minꢀ1, 220 nm): tr (minor) ¼ 17.8 min, tr (major) ¼ 20.8 min.
combined and washed with brine, dried over MgSO4 and
concentrated at reduced pressure. The residue was puried by
silica gel column chromatography to afford the esomeprazole
(56.7 mg, 48% yield, 99% ee). 1H NMR (400 MHz, DMSO) d 11.81
Experimental procedure for the gram scale synthesis of 2b
A mixture of Mn(OTf)2 (11. 1 mg, 0.032 mmol) and L2 (15.2 mg, (s, 2H), 7.68 (s, 1H), 7.53 (d, J ¼ 8.3 Hz, 1H), 7.29 (dd, J ¼ 8.3, 1.5
0.032 mmol) in CH3CN (5 mL) was stirred at room temperature Hz, 1H), 3.75 (s, 3H), 2.86–2.66 (m, 2H), 1.64–1.52 (m, 1H), 1.45
for 8 h. To the solution of manganese complex was added 1b (m, 1H), 0.91 (t, J ¼ 7.8 Hz, 3H); 13C {1H} NMR (100 MHz, DMSO)
(1.0 g, 6.30 mmol), adamantane carboxylic acid (227 mg, d 155.5, 149.7, 137.2, 117.8, 59.3, 53.6, 16.5, 14.0; HRMS (ESI-
1.26 mmol) and IPA (10 mL). Then decrease the temperature to TOF) m/z calcd for C12H15N3O3S [M + H]+ 282.0912, found
ꢀ20 ꢁC, 50% H2O2 (514 mg, 7.56 mmol) was added dropwise to 282.0918; HPLC (DAICEL OB-H, hexane–isopropanol 80 : 20,
the stirring reaction over 1 min and the mixture was stirred at ow rate: 1.0 mL minꢀ1, 220 nm): tr (minor) ¼ 11.4 min, tr
ꢀ20 ꢁC for 2 h. The reaction was quenched by adding the sat. aq. (major) ¼ 16.4 min.
46552 | RSC Adv., 2014, 4, 46545–46554
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27 M. Hinch, O. Jacques, C. Drago, L. Caggiano, R. F. Jackson,
C. Dexter, M. S. Anson and S. J. Macdonald, J. Mol. Catal.
A: Chem., 2006, 251, 123–128.
Acknowledgements
This work was gratefully nancially supported by the National
28 I. Mohammadpoor-Baltork, M. Hill, L. Caggiano and
R. F. Jackson, Synlett, 2006, 2006, 3540–3544.
29 B. Pelotier, M. S. Anson, I. B. Campbell, S. J. Macdonald,
G. Priem and R. F. Jackson, Synlett, 2002, 2002, 1055–1060.
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