Chiral phosphoric acid-catalyzed asymmetric oxidation of aryl alkyl sulfides and aldehyde-derived 1,3-dithianes: Using aqueous hydrogen peroxide as the terminal oxidant

Article abstract of DOI:10.1002/adsc.201100810

(R)-1,1'-Binaphthyl-2,2'-diol (R-BINOL) derived chiral phosphoric acids have been explored as organocatalysts for the asymmetric oxidation of a series of aryl alkyl sulfides and 1,3-dithianes derived from aldehydes with aqueous hydrogen peroxide (H₂O₂) as the terminal oxidant. The enantiomerically enriched sulfoxides are obtained in moderate to excellent yield (up to 99%) with excellent diastereoselectivity (up to >99:1 dr) and moderate to good enantioselectivity (up to 91:9 er). In particular, the present protocol stereoselectively provides an efficient access to enantiomerically enriched aryl alkyl sulfoxides and dithioacetal mono-sulfoxides, which strictly restrains the formation of the undesirable by-products: sulfones or disulfoxides. The tracking experiments also verify that this approach proceeds via a direct sulfoxidation process, instead of a kinetic resolution route by overoxidation of the resulting sulfoxides. Copyright

Full text of DOI:10.1002/adsc.201100810

FULL PAPERS
DOI: 10.1002/adsc.201100810
Chiral Phosphoric Acid-Catalyzed Asymmetric Oxidation of
Aryl Alkyl Sulfides and Aldehyde-Derived 1,3-Dithianes: Using
Aqueous Hydrogen Peroxide as the Terminal Oxidant
Zhao-Min Liu,a Hua Zhao,b Mei-Qiu Li,a Yu-Bao Lan,b Qi-Bo Yao,b
Jing-Chao Tao,b,* and Xing-Wang Wanga,*
a
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials
Science, Soochow University, Suzhou 215123, Peopleꢀs Republic of China
Fax : (+86)-512-6588-0378; e-mail: wangxw@suda.edu.cn
Department of Chemistry, Zhengzhou University, Zhengzhou 450001, Peopleꢀs Republic of China
b
Fax : (+86)-371-6776-7200; e-mail: jctao@zzu.edu.cn
Received: October 18, 2011; Revised: December 7, 2011; Published online: April 13, 2012
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201100810.
Abstract: (R)-1,1’-Binaphthyl-2,2’-diol (R-BINOL) sulfoxides and dithioacetal mono-sulfoxides, which
derived chiral phosphoric acids have been explored strictly restrains the formation of the undesirable by-
as organocatalysts for the asymmetric oxidation of products: sulfones or disulfoxides. The tracking ex-
a series of aryl alkyl sulfides and 1,3-dithianes de- periments also verify that this approach proceeds via
rived from aldehydes with aqueous hydrogen perox- a direct sulfoxidation process, instead of a kinetic
ide (H2O2) as the terminal oxidant. The enantiomeri- resolution route by overoxidation of the resulting
cally enriched sulfoxides are obtained in moderate to sulfoxides.
excellent yield (up to 99%) with excellent diastereo-
selectivity (up to >99:1 dr) and moderate to good
enantioselectivity (up to 91:9 er). In particular, the Keywords: asymmetric oxidation; chiral phosphoric
present protocol stereoselectively provides an effi- acids; 1,3-dithianes; hydrogen peroxide; organocatal-
cient access to enantiomerically enriched aryl alkyl ysis; sulfoxides
Introduction
Modena group.[7] Today, a variety of chiral catalysts,
mainly transition metal complexes based on titani-
Optically active sulfoxides play a crucial role in asym- um,[8] vanadium,[8b,9] manganese,[10] iron[11] and so
metric synthesis as chiral auxiliaries or chiral li- on,[12] have been applied to the asymmetric oxidation
gands.[1] Furthermore, due to their important biologi- of a wide range of sulfides with different sources of
cal activity,[2] many chiral sulfoxides, such as the
proton-pump inhibitor esomeprazole[3] and the selec-
tive NK2 antagonist ZD7944,[4] have also attracted
a great deal of interest in the pharmaceutical industry
(Figure 1).
Many efficient approaches have been developed to
obtain the enantiomerically pure sulfoxides over the
past three decades.[1a,5] Among all methods described
so far, the asymmetric oxidation of prochiral sulfides
is undoubtedly the most direct and easy approach for
the preparation of chiral sulfoxides. Besides biological
oxidation[5e,f,6] and sulfoxidation with stoichiometric
chiral oxidant,[5d–f] several chemo-catalytic systems for
enantioselective sulfoxidation have been developed
since the initial reports by the Kagan group and pharmaceutical industry.
Figure 1. Structures of representative chiral sulfoxides in the
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Chiral Phosphoric Acid-Catalyzed Asymmetric Oxidation of Aryl Alkyl Sulfides
Table 1. Asymmetric oxidation of thioanisole 2a with H2O2
catalyzed by chiral phosphoric acids.[a]
oxygen donors. Most transition metal catalystic sys-
tems are usually highly enantioselective (ee>90%)
with low catalyst loadings (1–2 mol%), however, high
enantioselectivities are partly achieved by overoxida-
tion of one sulfoxide enantiomer to the sulfone at the
expense of the yield in some cases. More importantly,
the removal of metal traces is a permanent problem
in the pharmaceutical industry. Thus, exploring for en-
vironmentally friendly, metal-free, stereoselective sul-
foxidation process is still challenging and in high
demand for organic chemists.
Over the recent years, asymmetric organocatalysis
has emerged as a new, exciting and environmentally
friendly methodology in organic chemistry, comple-
menting bio- and metal catalysis.[13] However, organo-
catalytic methods for the synthesis of optically active
sulfoxides have been only marginally studied, and
only a limited number of asymmetric organocatalytic
sulfoxidations have been reported up to date.[5b,d,f,14]
Since the pioneering studies of the groups of Akiya-
ma and Terada in 2004,[15] chiral BINOL-derived
phosphoric acids, which contain both a Brønsted
acidic site and Lewis basic site, have proven to be ef-
ficient organocatalysts for a large number of impor-
tant enantioselective transformations.[16] To the best
of our knowledge, however, chiral Brønsted acid cat-
alysis has never been used to promote asymmetric
sulfoxidation reactions. Herein, we report our prelimi-
nary results on the example of the chiral phosphoric
acid-catalyzed asymmetric oxidation of alkyl aryl sul-
fides and aldehyde derived cyclic dithioacetals with
aqueous hydrogen peroxide (H2O2) as the oxidant,
furnishing the corresponding sulfoxides.
Entry
Cat. 1
Time [h]
Yield [%][b]
er[c]
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1h
1i
40
60
60
24
60
24
60
60
60
24
60
45
24
40
48
140
91
86
83
66
88
91
77
85
31
37
87
89
95
87
65
27
47:53
73:27
75:25
58:42
54:46
85:15
69:31
68:32
57:43
65:35
48:52
82:18
86:14
86:14
89:11
56:44
9
10
11
12[d]
13[e]
14[f]
15[g]
16[g,h]
1j
1k
1f
1f
1f
1f
1f
[a]
Reactions were performed with 2a (0.3 mmol), 50%
H2O2 (0.45 mmol, 1.5 equiv.) and catalyst 1 (10 mol%) in
CHCl3 (1.0 mL) at À108C, unless otherwise noted.
Isolated yield.
The enantiomeric ratios (er) of (S)-3a/(R)-3a were deter-
mined by chiral HPLC analysis according to the litera-
ture method.[7a]
The reaction was carried out with 5 mol% catalyst.
The reaction was carried out with 15 mol% catalyst.
The reaction was carried out at À208C.
The reaction was carried out at À408C.
The catalyst was purified on silica gel, without treatment
by 4N HCl.
[b]
[c]
[d]
[e]
[f]
[g]
[h]
Results and Discussion
A preliminary examination of the chiral phosphoric
acid 1a (10 mol%) catalyzed oxidation of thioanisole
2a using 1.5 equivalents of aqueous H2O2 (50%) as
the oxidant in CHCl3 at À108C afforded phenyl
methyl sulfoxide 3a with good catalytic activity (40 h,
91% yield), albeit with very poor enantioselectivity
(47:53 er) (Table 1, entry 1). Notably, reaction almost
did not occur in the absence of 1a under otherwise
identical experimental conditions. These results clear-
ly showed the accelerating effect of the phosphoric
acid in the oxidation of thioanisole 2a and prompted
us to improve the catalytic performance of the phos-
phoric acids by tuning the steric and electronic prop-
erties of the 3,3’-substituents (Figure 2). Both the cat-
alytic efficiency and asymmetric induction are strong-
ly dependent on the solvents used. Among the variety
of solvents examined for the reaction, CHCl3 is the
best choice in terms of the enantiocontrol (see the
Supporting Information; Table S1).
Figure 2. (R)-BINOL-derived chiral phosphoric acids.
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Table 2. Asymmetric oxidation of aryl alkyl sulfides with H2O2 catalyzed by 1f.[a]
Entry
Sulfide
Time [h]
Yield [%][b]
er[c,d]
1
2
3
4
5
6
7
8
9
2a: Ar=C6H5, R=CH3
48
115
88
144
115
115
144
115
88
65
89
92
35
78
84
42
74
68
89:11(S)
90:10(S)
85:15(S)
87:13(S)
87:13(S)
86:14(S)
83:17(S)
85:15(S)
91:9(S)
2b: Ar=4-CH3C6H4, R=CH3
2c: Ar=4-MeOC6H4, R=CH3
2d: Ar=2-BrC6H4, R=CH3
2e: Ar=4-BrC6H4, R=CH3
2f: Ar=4-ClC6H4, R=CH3
2g: Ar=4-NO2C6H4, R=CH3
2h: Ar=C6H5, R=Et
2i: Ar=C6H5, R=Bn
[a]
Reactions were performed with 2 (0.3 mmol), 50% H2O2 (0.45 mmol, 1.5 equiv.) and 1f (10 mol%) in CHCl3 (1.0 mL) at
À408C.
[b]
[c]
[d]
Isolated yield.
Determined by chiral HPLC analysis.
The absolute configurations were assigned by comparing optical rotations with known literature data.
Under the preliminarily optimized reaction condi- silica gel.[17] We also noticed this key point and com-
tions, a series of (R)-BINOL-derived phosphoric acids pared the catalytic performances of only silica gel-pu-
with varying substituents at the 3- and 3’-positions of rified phosphoric acid and metal-free phosphoric acid,
the binaphthyl scaffold were tested, and the results i.e., washed with 4N HCl (aqueous) in THF after pu-
are listed in Table 1. Phosphoric acids 1d, 1e, 1i and rification by chromatography. To our great surprise,
1k showed disappointing results, giving phenyl methyl a significant drop in terms of both yield and enantio-
sulfoxide 3a with low enantioselectivities (48:52–58:42 selectivity was observed when using chiral phosphoric
ers) (entries 4, 5, 9 and 11). To our delight, several acid 1f without treatment by 4N HCl as the catalyst
other phosphoric acid catalysts afforded the desired (Table 1, entry 16 vs. entry 15). In addition, a range of
product with moderate to good enantioselectivities other hydroperoxides were also tested but gave inferi-
(entries 2, 3, 6–8 and 10). Chiral phosphoric acid 1f or results (see the Supporting Information; Table S2).
bearing the 1-naphthyl group was proven to be the With a balance of activity and stereoselectivity, hydro-
optimal catalyst, affording (S)-3a in 91% yield with gen peroxide was finally chosen as the optimal oxi-
an encouraging enantiomeric ratio of 85:15 (entry 6). dant.
When the catalyst loading of 1f was dropped to
With the optimized conditions in hand (10 mol% of
5 mol%, we found that the reaction became much 1f as the catalyst, at À408C in chloroform and using
slower and a prolonged reaction time of 45 h (instead 1.5 equivalents of aqueous H2O2 as the oxidant), the
of 24 h) was necessary to reach the same chemical substrate scope and limitations of this new protocol
yield, albeit with slightly lower enantioselectivity were then investigated by application to a variety of
(entry 12). However, on increasing the catalyst load- simple aryl alkyl sulfides. As shown in Table 2, the re-
ing to 15 mol%, no remarkable enhancement to the action involving all substrates afforded the corre-
yield and the enantioselectivity was achieved sponding sulfoxides with moderate to good enantio-
(entry 13). In addition, the reaction temperature also meric ratios (83:17–91:9), albeit with a slight variation
had a significant influence on the yield and enantiose- in the reactivity, as evidenced by the isolated yields of
lectivity of this transformation (entries 14 and 15). the desired products (35–92%). It has been observed
The enantiomeric ratio of product 3a could be im- that the electronic effect of the substituent on the
proved to 86:14 when the reaction temperature was phenyl ring of aryl methyl sulfides plays a significant
lowered to À208C (entry 14). Pleasingly, the er value role in yields and enantioselectivities. For aryl methyl
could be further enhanced to 89:11 when the reaction sulfides 2b and 2c bearing electron-donating substitu-
was carried out at À408C (entry 15).
ents (Me, OMe) at the para-position on the phenyl
In recent years, several research groups have found group, the desired products 3b and 3c could be ob-
that chiral phosphoric acids, after purification by tained in high yields but with varying levels of enan-
chromatography, should be further washed with hy- tiomeric ratios from 85:15 to 90:10 (entries 2 and 3).
drochloric acid to remove the metal impurities, such Aryl methyl sulfides 2d–2g bearing electron-with-
as alkali or alkaline-earth metal salts absorbed from drawing substituents (Br, Cl, NO2) were oxidized in
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Chiral Phosphoric Acid-Catalyzed Asymmetric Oxidation of Aryl Alkyl Sulfides
reduced yields, but still acceptable enantiomeric
The dithioacetal mono-oxides have reversed polari-
ratios were obtained after prolonged reaction time ty compared to carbonyl compounds, and their enan-
(entries 4–7). Furthermore, the position of the sub- tiomerically enriched derivatives could serve as chiral
stituent on the phenyl group has a significant impact masked acyl groups in various transformations.[18]
on the catalytic activity. Sulfide 2d with an ortho- Thus, much effort has been directed toward the devel-
bromo group on the phenyl ring was oxidized more opment of efficient methods for the preparation of
slowly than sulfide 2e bearing a para-bromo group, al- optically active mono-oxides of cyclic dithio-acetals,
though the same level of enantiomeric ratio was such as 1,3-dithiolane and 1,3-dithiane, and several ef-
found (entry 4 vs. entry 5). In addition, phenyl ethyl ficient asymmetric sulfoxidations of cyclic dithioace-
sulfide 2h and phenyl benzyl sulfide 2i were also ex- tals have been reported so far.[9j,12b,19] However, to the
amined for this transformation and gratefully, the sub- best of our knowledge, no one has so far reported on
strate 2i furnished the desired product 3i in good the highly stereoselective mono-oxidation of cyclic di-
yield and with the best enantioselectivity (up to 91:9 thioacetals carried out through the organic molecular
er) (entries 8 and 9). catalysis in the presence of a substoichiometric cata-
The stereochemistry of all the representative sulf- lyst loading.
oxides obtained was determined as the S configura-
Encouraged by the promising results of the asym-
tion, which was unambiguously assigned by compari- metric sulfoxidation of aryl alkyl sulfides, we further
son of their optical rotations with literature data. examined the scope of the chiral phosphoric acid-cat-
Under the conditions described, no overoxidation by- alyzed oxidation of a variety of 1,3-dithianes derived
product sulfones were detected by TLC or NMR, from aromatic aldehydes. The reactions were per-
which indicates that the enantioselectivity is a direct formed with 0.15 mmol 1,3-dithianes and 1.2 equiva-
result of the asymmetric sulfide oxidation and not of lents of aqueous H2O2 (50%) under the above opti-
a kinetic resolution by overoxidation of the resulting mized reaction conditions. The representative results
sulfoxides.
are summarized in Table 3. All nineteen substrates
Table 3. Asymmetric oxidation of 1,3-dithianes with H2O2 catalyzed by 1f.[a]
Entry
4: Ar
Time [h]
Yield [%][b]
dr (trans:cis)[c]
er[d]
1
2
3
4
5
6
7
8
4a: C6H5
88
67
95
99
99
87
76
98
95
99
99
98
94
79
75
93
60
97
91
98
>99:1
94:6
>99:1
>99:1
>99:1
93:7
>98:2
90:10
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
88:12
97:3
83:17
78:22
80:20
81:19
78:22
80:20
84:16
81:19
82:18
85:15
85:15
87:13
83:17
85:15
85:15
79:21
83:17
83:17
81:19
(1S,2S)[e]
ACHTUNGTRENNUNG
4b: 2-CH3OC6H4
4c: 3-CH3C6H4
4d: 4-CH3C6H4
4e: 4-i-PrC6H4
4f: 2-FC6H4
4g: 4-FC6H4
4h: 2-ClC6H4
4i: 3-ClC6H4
4j: 4-ClC6H4
4k: 4-BrC6H4
4l: 3-NO2C6H4
4m: 4-NO2C6H4
4n: 4-CNC6H4
4o: 4-CF3C6H4
4p: 2,4-Cl2C6H3
4q: 1-naphthyl
4r: 2-naphthyl
4s: 2-thienyl
144
137
144
137
137
140
144
144
144
144
110
110
110
140
137
144
110
140
9
10
11
12
13
14
15
16
17
18
19
97:3
98:2
[a]
Reactions were performed with 4 (0.15 mmol), 50% H2O2 (0.18 mmol, 1.2 equiv.) and 1f (10 mol%) in CHCl3 (0.5 mL) at
À408C.
[b]
[c]
[d]
[e]
Isolated yield.
1
Determined by H NMR spectroscopic analysis according to references.[19a,c]
.
Determined by chiral HPLC analysis.
The absolute configurations were assigned by comparing optical rotation with known literature data.[12b]
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Zhao-Min Liu et al.
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gave moderate to excellent yields (67–99%), excellent
diastereoselectivities (up to >99:1 dr) and moderate
to good enantiomeric ratios (up to 87:13). Generally,
substrates 4b–e bearing electron-donating substituents
(Me, OMe, i-Pr) usually gave slightly lower enantio-
meric ratios than substrates 4f–o containing electron-
withdrawing substituents (F, Cl, Br, NO2, CN, CF3).
Intriguingly, the substrate 4j bearing the para chloro-
substituent gave a higher er value than its two other
(ortho and meta) isomers 4h and 4i (entries 8–10); A
similar regulation is also observed for the fluoro-sub-
stituted 1,3-dithianes 4f and 4g (entries 6 and 7). In
contrast, the substrate 4m with a para nitro group
gave only 83:17 er, which was inferior to the 87:13 er
^
Figure 3. Effect of reaction time on the ee values ( ) and
&
of its meta isomer 4l (entries 12 and 13). It is notewor- yields ( ) of 3a in the asymmetric oxidation of 2a
(0.3 mmol) with 50% H2O2 (1.5 equiv.) catalyzed by 1f
(10 mol%) in CHCl3 (1.0 mL) at À108C.
thy that for the reactions involving substrates 4b, 4f,
4h and 4p bearing a substitutent at the ortho position
of the phenyl ring there seems to be a remarkable
detrimental effect on the diastereoselectivities proba-
bly due to the steric hindrance (entries 2, 6, 8 and 16).
Moreover, the 1,3-dithianes 4q–s containing heteroar-
omatic or fused aromatic rings were also suitable sub-
strates for this reaction, affording the corresponding
products 5q–s in 91–98% yields with 97:3–98:2 drs
and 81:19–83:17 ees (entries 17–19). It should be
noted that no overoxidation to sulfones or disulfox-
ides was observed for the dithioacetal mono-oxidation
reaction.[20]
Figure 4. Proposed transition state.
In order to further probe the real stereoselective
process, the effects of the amount of aqueous H2O2 chiral phosphoric acid,[22] a plausible working model
and reaction time on the enantioselective sulfoxida- for the present catalytic system is proposed in
tion were explored by utilizing thioanisole 2a as the Figure 4, where the “large” group RL represents the
model substrate in the presence of 10 mol% of cata- aryl group for aryl alkyl sulfides or the 2-substituted
lyst 1f. When the amount of 50% H2O2 was raised alkyl group for 1,3-dithiane. The hydrogen peroxide is
from 1.5 to 2.0 equivalents at À108C after 24 h, still supposed to be activated by a double hydrogen-bond-
no overoxidation product of the sulfone was detected, ing interaction with the bifunctional catalyst 1f, and
albeit the yield of the desired product was increased then a stereoselectively nucleophilic attack of the sul-
À
to 95% and the enantiomeric ratio was slightly de- fide S atom on the O O bond occurs because of the
creased to 84:16 relative to that of a 1.5 equivalent chiral environment created by the 1,1’-binaphthyl
amount of 50% H2O2 (Table 1, entry 6). This indicat- backbone and the congested 3- and 3’-substitutents of
ed that the surplus H2O2 did not cause kinetic resolu- the catalyst 1f as shown in Figure 4.
tion of the resulting sulfoxide. On the other hand,
a profile of time-enantioselectivity and reactivity was
depicted for seven parallel oxidation reactions of 2a Conclusions
with a 1.5 equivalent amount of 50% H2O2 at À108C
in Figure 3. When the reaction time was increased In summary, we have developed a new asymmetric
from 2 h to 40 h, yields of the sulfoxide were in- oxidation of aryl alkyl sulfides and 1,3-dithianes de-
creased steadily but ee values were almost retained. rived from aldehydes using BINOL-derived chiral
On the basis of these studies, we could deduced that phosphoric acids as the organocatalysts. With the eco-
the oxidation of sulfides catalyzed by chiral phospho- nomic and environmentally benign aqueous H2O2
ric acid proceeds via a direct enantioselective sulfoxi- (50%) as the oxidant, the corresponding optically
dation process, instead of a kinetic resolution route active sulfoxides can be obtained in moderate to ex-
by overoxidation of the resulting sulfoxides.
cellent yields (up to 99%) with good to excellent dia-
On the basis of the absolute configuration observed stereoselectivities (up to 99:1 dr) and moderate to
for the products, the commonly accepted mechanism good enantioselectivities (up to 91:9 er). Remarkably,
for sulfide oxidation with hydrogen peroxide[21] and the present protocol stereoselectively furnishes the
Dingꢀs activation mode of hydrogen peroxide by desired enantiomerically enriched aryl alkyl sulfox-
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Chiral Phosphoric Acid-Catalyzed Asymmetric Oxidation of Aryl Alkyl Sulfides
ides and dithioacetal mono-sulfoxides, but no overoxi- General Procedure for the Asymmetric Oxidation of
dation to sulfones or disulfoxides was observed in any Aryl Alkyl Sulfides
of the cases. The tracking experiments also support
that this approach proceeds via a direct sulfoxidation
and a ground glass stopper was charged with 18 mg 1f
A 10-mL test tube equipped with a Teflon-coated stir bar
process, instead of a kinetic resolution route by over-
oxidation of the resulting sulfoxides. In addition, sali-
ent features endowed with the present protocol also
include it being environmentally friendly, low-cost,
metal-free and operationally simple. This work is the
first application of the stronger Brønsted acids into
the asymmetric sulfoxidation, and studies on the fur-
ther improvement of the catalytic system, practicality
of the present protocol and details of the mechanism
are underway in our laboratory.
(0.03 mmol), 0.3 mmol sulfide 2 and 1 mL CHCl3. The mix-
ture was stirred for 30 min at À408C, and then 1.5 equiv. of
aqueous H2O2 (50%) were slowly added at this temperature.
The reaction mixture was stirred for the time given in
Table 2 at À408C and then excess H2O2 was decomposed
with aqueous NaHSO3. The product 3 was isolated by prep-
arative TLC or flash column chromatography on silica gel
with petroleum ether/EtOAc 2:3 or CH2Cl2/MeOH 100:1 as
the eluent. The enantiomeric excess was determined by
chiral HPLC analysis.
General Procedure for the Asymmetric Oxidation of
1,3-Dithianes
Experimental Section
A 10-mL test tube equipped with a Teflon-coated stir bar
and a ground glass stopper was charged with 9 mg 1f
(0.015 mmol), 0.15 mmol 1,3-dithiane 4 and 0.5 mL CHCl3.
The mixture was stirred for 30 min at À408C, and then
1.2 equiv. of aqueous H2O2 (50%) were slowly added at this
temperature. The reaction mixture was stirred for the time
given in Table 3 at À408C and then excess H2O2 was decom-
posed with aqueous NaHSO3. The crude product was puri-
fied by flash column chromatography (CH2Cl2/MeOH
100:1) to give the desired monoxide as diastereomeric mix-
General
Unless otherwise stated, all reagents were purchased from
commercial suppliers and used without further purification.
All reactions were carried out in air and using undistilled
solvents, without any precautions to exclude air and mois-
ture unless otherwise noted. Reactions were monitored by
thin-layer chromatography (TLC) on silica gel precoated
glass plates (0.2Æ0.03 mm thickness, GF-254, particle size
0.01–0.04 mm) from Yantai Chemical Industry Research In-
stitute, P. R. China. Chromatograms were visualized by fluo-
rescence quenching with UV light at 254 nm. Flash column
chromatography was performed using silica gel (particle size
0.04–0.05 mm) from Yantai Chemical Industry Research In-
stitute, P. R. China. Melting points were measured on an X-
1
ture. The diastereomeric ratio was determined by H NMR
spectroscopic analysis and the enantiomeric ratio was deter-
mined by chiral HPLC analysis.
(S)-(À)-Phenyl methyl sulfoxide (3a): Colorless oil; yield:
65%; 89:11 er; HPLC (Chiralcel OD-H, hexane/i-PrOH=
90/10, flow rate: 1.0 mLminÀ1, l=254 nm): tminor =12.6 min,
major =14.6 min; [a]D26: À85.4 (c 0.79, acetone) [lit.:[7a] [a]D20:
5
melting point apparatus and uncorrected. 1H and
t
13C NMR spectra were recorded in CDCl3 on Varian Inova
300 MHz or 400 MHz spectometers. Tetramethylsilane
+130 (c 1.7, acetone) for (R)-isomer, 89% ee]; IR (KBr):
n=3056, 2913, 1443, 1038, 750, 693 cmÀ1
;
1H NMR
1
(TMS) served as internal standard (0 ppm) for H NMR and
(400 MHz, CDCl3): d=7.71–7.60 (m, 2H), 7.57–7.46 (m,
3H), 2.73 (s, 3H); 13C NMR (100 MHz, CDCl3): d=145.7,
131.2, 129.5, 123.6, 44.0; ESI-MS: m/z=141.0 [M+H]+; HR-
MS-ESI: m/z=141.0370, calcd. for C7H9OS [M+H]+:
141.0374.
CDCl3 was used as internal standard (77.0 ppm) for
13C NMR. IR spectra were recorded on a Varian 1000 FT-IR
spectrometer. Mass spectra were carried out using an Agi-
lent 6120 Quadrupole LC/MS system with an ESI resource.
High-resolution mass spectra (HR-MS) were determined on
a Micromass GCT-TOF mass spectrometer with an ESI
source. High-performance liquid chromatography (HPLC)
was performed on Agilent 1200 Series or SHIMADZU LC-
6 A instrument equipped with a DAD detector on chiral col-
umns [Chiralcel OD-H, Chiralcel OB-H, Chiralcel OJ-H or
Chiralpak AD-H (Daicel Chemical Ind., Ltd., F 0.46 cmꢂ
25 cm)]. Optical rotations were measured on an Autopol IV
polarimeter and reported as follows: [a]D (c in g per
100 mL, solvent). The 1,3-dithianes were prepared from 1,3-
propanedithiol and various aromatic aldehydes according to
the reported methods.[23]
(S)-(À)-4-Tolyl methyl sulfoxide (3b): White solid; yield:
89%; 90:10 er; mp 72–738C; HPLC (Chiralcel OD-H,
hexane/i-PrOH=90/10, flow rate: 0.5 mLminÀ1, l=254 nm):
t
minor =23.4 min, tmajor =24.9 min; [a]2D6: À96.8 (c 1.1, acetone)
[lit.:[7a] [a]2D0: +132 (c 2.0, acetone) for (R)-isomer, 91% ee];
IR (KBr): n=3040, 2928, 1592, 1494, 1089, 1049, 1013, 972,
817, 509 cmÀ1; H NMR (400 MHz, CDCl3): d=7.54 (d, J=
1
8.0 Hz, 2H), 7.33 (d, J=8.0 Hz, 2H), 2.71 (s, 3H), 2.42 (s,
3H); 13C NMR (100 MHz, CDCl3): d=142.3, 141.4, 129.9,
123.4, 43.9, 21.3; ESI-MS: m/z=155.0 [M+H]+; HR-MS-
ESI: m/z=155.0527, calcd. for C8H11OS [M+H]+: 155.0531.
(S)-(À)-4-Methoxyphenyl methyl sulfoxide (3c): Colorless
oil; yield: 92%; 85:15 er; HPLC (Chiralcel OD-H, hexane/i-
PrOH=90/10, flow rate: 0.5 mLminÀ1, l=254 nm): tminor
=
38.2 min, tmajor =41.5 min; [a]2D6: À90.4 (c 1.2, CHCl3) [lit.:[7a]
[a]2D0: À102 (c 2.0, acetone) for (S)-isomer, 86% ee]; IR
(KBr): n=3014, 2910, 1595, 1497, 1256, 1090, 1027,
Synthesis of Chiral Phosphoric Acids
All of the chiral phosphoric acid catalysts are known com-
pounds[24] and 1a,[24a] 1b,[24b] 1c,[24c] 1d,[24d] 1e,[24b] 1f,[24b] 1g,[24b]
1h,[24b] 1i,[24b] 1j,[24e] and 1k[24f] were prepared according to
the reported procedures, respectively.
832 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=7.60 (d, J=
8.6 Hz, 2H), 7.04 (d, J=8.6 Hz, 2H), 3.86 (s, 3H), 2.70 (s,
3H); 13C NMR (100 MHz, CDCl3): d=161.8, 136.5, 125.4,
Adv. Synth. Catal. 2012, 354, 1012 – 1022
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1017

Zhao-Min Liu et al.
FULL PAPERS
114.8, 55.5, 43.9; ESI-MS: m/z=171.0 [M+H]+; HR-MS-
ESI: m/z=171.0483, calcd. for C8H11O2S [M+H]+: 171.0480.
(S)-(À)-2-Bromophenyl methyl sulfoxide (3d): Colorless
oil; yield: 35%; 87:13 er; HPLC (Chiralcel OB-H, hexane/i-
129.0, 124.0, 50.1, 5.8; ESI-MS: m/z=155.0 [M+H]+; HR-
MS-ESI: m/z=155.0529, calcd. for C8H11OS [M+H]+:
155.0531.
(S)-(À)-Phenyl benzyl sulfoxide (3i): White solid; yield:
68%; 91:9 er; mp 114–1168C; HPLC (Chiralcel OD-H,
hexane/i-PrOH=90/10, flow rate: 0.5 mLminÀ1, l=254 nm):
PrOH=80/20, flow rate: 0.5 mLminÀ1, l=210 nm): tminor
=
23.3 min, tmajor =15.8 min; [a]2D6: À91.7 (c 0.56, THF) [lit.:[25]
[a]2D5: +251 (c 1.0, THF) for (R)-isomer, >99% ee]; IR
t
minor =27.7 min, tmajor =32.9 min; [a]2D6: À164.2 (c 0.90, ace-
(KBr): n=3060, 2995, 1447, 1058, 759 cmÀ1
;
1H NMR
tone) [lit.:[11d] [a]2D5: À169.8 (c 1.0, acetone) for (S)-isomer,
(400 MHz, CDCl3): d=7.98–7.91 (m, 1H), 7.62–7.53 (m,
2H), 7.42–7.34 (m, 1H), 2.83 (s, 3H); 13C NMR (100 MHz,
CDCl3): d=145.2, 132.8, 132.2, 128.7, 125.6, 118.3, 41.8; ESI-
MS (%): m/z=218.8 (98) and 220.8 (100) [M+H]+ for 79Br
and 81Br isotopic pattern; HR-MS-ESI (%): m/z=218.9472
(98), calcd. for C7H879BrO32S [M+H]+: 218.9474 and m/z=
220.9450 (100), calcd. for C7H881BrO34S [M+H]+: 220.9459.
(S)-(À)-4-Bromophenyl methyl sulfoxide (3e): White
solid; yield: 78%; 87:13 er; mp 59–608C; HPLC (Chiralcel
OB-H, hexane/i-PrOH=80/20, flow rate: 0.5 mLminÀ1, l=
210 nm): tminor =24.2 min, tmajor =17.4 min; [a]2D6: À64.0 (c 1.1,
acetone) [lit.:[7a] [a]D25: +77 (c 1.8, acetone) for (R)-isomer,
80% ee]; IR (KBr): n=3072, 2925, 1571, 1470, 1043, 1007,
79% ee]; IR (KBr): n=3060, 2976, 1560, 1034, 746 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=7.45–7.32 (m, 5H), 7.29–
7.12 (m, 3H), 7.01–6.86 (m, 2H), 4.08 and 4.00 (AB, J=
12.6 Hz, 2H); 13C NMR (100 MHz, CDCl3): d=142.6, 131.1,
130.3, 129.0, 128.8, 128.39, 128.2, 124.4, 63.5; ESI-MS: m/z=
216.9 [M+H]+; HR-MS-ESI: m/z=217.0688, calcd. for
C13H13OS [M+H]+: 217.0687.
(+)-trans-(1S,2S)-2-Phenyl-1,3-dithiane
1-oxide
(5a):
White solid; yield: 67%; >99:1 dr, 83:17 er; mp 136–1378C;
HPLC (Chiralpak AD-H, hexane/i-PrOH=75/25, flow rate:
0.5 mLminÀ1, l=210 nm): tminor =27.2 min, tmajor =17.3 min;
[a]2D6: +74.1 (c 1.0, CHCl3) [lit.:[12b] [a]2D5: +117.4 (c 0.63,
CHCl3) for (1S,2S)-isomer, 99% ee]; IR (KBr): n=3070,
1
1
829, 722, 516 cmÀ1; H NMR (400 MHz, CDCl3): d=7.68 (d,
2913, 1453, 1037, 698 cmÀ1; H NMR (400 MHz, CDCl3): d
J=8.4 Hz, 2H), 7.53 (d, J=8.4 Hz, 2H), 2.73 (s, 3H);
13C NMR (100 MHz, CDCl3): d=144.6, 132.4, 125.3, 125.0,
43.9; ESI-MS (%): m/z=218.8 (98) and 220.8 (100) [M+
H]+ for 79Br and 81Br isotopic pattern; HR-MS-ESI (%): m/
z=218.9474 (98), calcd. for C7H879BrO32S [M+H]+:
218.9474 and m/z=220.9453 (100), calcd. for C7H881BrO34S
[M+H]+: 220.9459.
7.45–7.31 (m, 5H), 4.56 (s, 1H), 3.62–3.50 (m, 1H), 2.94–
2.82 (m, 1H), 2.80–2.62 (m, 2H), 2.57–2.46 (m, 1H), 2.44–
2.29 (m, 1H); 13C NMR (75 MHz, CDCl3): d=133.2, 129.1,
128.9, 128.5, 69.4, 54.5, 31.1, 29.3; ESI-MS: m/z=212.9 [M+
H]+; HR-MS-ESI: m/z=213.0400, calcd. for C10H13OS2 [M+
H]+: 213.0402.
(+)-trans-2-(2’-Methoxyphenyl)-1,3-dithiane 1-oxide (5b):
White solid; yield: 95%; 94:6 dr, 78:22 er; mp 149–1518C;
HPLC (Chiralpak OD-H, hexane/i-PrOH=90/10, flow rate:
0.8 mLminÀ1, l=210 nm): tminor =49.8 min; tmajor =55.4 min;
[a]2D6: +71.8 (c 0.98, CHCl3); IR (KBr): n=3070, 2962, 1493,
(S)-(À)-4-Chlorophenyl methyl sulfoxide (3f): Colorless
oil; yield: 84%; 86:14 er; HPLC (Chiralcel OB-H, hexane/i-
PrOH=80/20, flow rate: 0.5 mLminÀ1, l=254 nm): tminor
=
24.0 min, tmajor =16.6 min; [a]2D6: À72.8 (c 1.1, acetone) [lit.:[7a]
[a]2D5: +97 (c 2.0, acetone) for (R)-isomer, 78% ee]; IR
1036, 760 cmÀ1 1H NMR (300 MHz, CDCl3): d=7.51–7.38
;
(KBr): n=3092, 2970, 1578, 1090, 1052, 823, 742 cmÀ1
;
(m, 1H), 7.36–7.27 (m, 1H), 7.01 (t, J=7.5 Hz, 1H), 6.93 (d,
J=8.3 Hz, 1H), 5.28 (s, 1H), 3.87 (s, 3H), 3.62–3.51 (m,
1H), 2.98–2.74 (m, 2H), 2.68–2.59 (m, 1H), 2.57–2.46 (m,
1H), 2.45–2.26 (m, 1H); 13C NMR (75 MHz, CDCl3): d=
157.6, 130.2, 128.8, 121.7, 121.2, 111.2, 61.7, 55.8, 54.7, 31.6,
29.7; ESI-MS: m/z=242.9 [M+H]+; HR-MS-ESI: m/z=
243.0509, calcd. for C11H15O2S2 [M+H]+: 243.0508.
1H NMR (400 MHz, CDCl3): d=7.60 (d, J=8.4 Hz, 2H),
7.52 (d, J=8.4 Hz, 2H), 2.73 (s, 3H); 13C NMR (100 MHz,
CDCl3): d=144.1, 137.1, 129.6, 124.9, 44.0; ESI-MS (%): m/
z=174.9 (100) and 176.9 (38) [M+H]+ for 35Cl and 37Cl iso-
topic pattern; HR-MS-ESI (%): m/z=174.9977 (100), calcd.
for C7H835ClO32S [M+H]+: 174.9979 and m/z=176.9947
(38), calcd. for C7H837ClO34S [M+H]+: 176.9950.
(+)-trans-2-(3’-Methylphenyl)-1,3-dithiane 1-oxide (5c):
White solid; yield: 99%; >99:1 dr, 80:20 er; mp 143–1448C;
HPLC (Chiralpak OD-H, hexane/i-PrOH=70/30, flow rate:
1.0 mLminÀ1, l=210 nm): tminor =8.7 min, tmajor =12.4 min;
[a]2D6: +80.0 (c 0.99, CHCl3); IR (KBr): n=3035, 2910, 1035,
(S)-(À)-4-Nitrophenyl methyl sulfoxide (3g): White solid;
yield: 42%; 83:7 er; mp 115–1178C; HPLC (Chiralcel OJ-H,
hexane/i-PrOH=70/30, flow rate: 0.5 mLminÀ1, l=254 nm):
t
minor =31.4 min, tmajor =36.3 min; [a]2D6: À47.6 (c 1.1, CHCl3)
[lit.:[26] [a]25: +156.9 (c 0.75, CHCl3) for (R)-isomer, 99.3%
ee]; IR (DKBr): n=3098, 3018, 1600, 1519, 1343, 1048,
699 cmÀ1 1H NMR (300 MHz, CDCl3): d=7.41–7.10 (m,
;
4H), 4.52 (s, 1H), 3.61–3.50 (m, 1H), 2.93–2.62 (m, 3H),
2.60–2.24 (m, 2H), 2.36 (s, 3H); 13C NMR (75 MHz,
CDCl3): d=138.8, 133.1, 130.1, 129.3, 129.0, 125.7, 69.6, 54.7,
31.4, 29.5, 21.3; ESI-MS: m/z=226.9 [M+H]+; HR-MS-
ESI: m/z=227.0560, calcd. for C11H15OS2 [M+H]+:
227.0559.
852 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=8.41 (d, J=
8.7 Hz, 2H), 7.87 (d, J=8.7 Hz, 2H), 2.83 (s, 3H); 13C NMR
(100 MHz, CDCl3): d=153.1, 149.3, 124.5, 124.3, 43.7; ESI-
MS: m/z=185.9 [M+H]+; HR-MS-ESI: m/z=186.0227,
calcd. for C7H8NO3S [M+H]+: 186.0225.
(S)-(À)-Phenyl ethyl sulfoxide (3h): Colorless oil; yield:
74%; 85:15 er; HPLC (Chiralcel OD-H, hexane/i-PrOH=
90/10, flow rate: 0.5 mLminÀ1, l=254 nm): tminor =20.3 min,
(+)-trans-2-(4’-Methylphenyl)-1,3-dithiane 1-oxide (5d):
White solid; yield: 99%; >99:1 dr, 81:19 er; mp 165–1678C;
HPLC (Chiralpak OD-H, hexane/i-PrOH=70/30, flow rate:
1.0 mLminÀ1, l=254 nm): tminor =9.5 min, tmajor =16.2 min;
[a]2D6: +88.6 (c 1.0, CHCl3); IR (KBr): n=3025, 2900, 1513,
t
major =24.7 min; [a]D26: À56.0 (c 0.33, EtOH) [lit.:[11d] [a]D
À169.1 (c 1.4, EtOH) for (S)-isomer, 82% ee]; IR (KBr):
n=3060, 2979, 1443, 1087, 1044, 749 cmÀ1
;
1H NMR
1039, 851, 751 cmÀ1 1H NMR (300 MHz, CDCl3): d=7.31
;
(400 MHz, CDCl3): d=7.67–7.56(m, 2H), 7.56–7.45 (m,
G
(d, J=8.0 Hz, 2H), 7.20 (d, J=8.0 Hz, 2H), 4.52 (s, 1H),
3.60–3.49 (m, 1H), 2.92–2.61 (m, 3H), 2.56–2.25 (m, 2H),
2.34 (s, 3H); 13C NMR (75 MHz, CDCl3): d=139.3, 130.2,
3H), 2.99–2.85 (m, 1H), 2.84–2.70 (m, 1H), 1.19 (t, J=
6.5 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=143.1, 130.9,
1018
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 1012 – 1022

Chiral Phosphoric Acid-Catalyzed Asymmetric Oxidation of Aryl Alkyl Sulfides
129.8, 128.5, 69.4, 54.6, 31.4, 29.5, 21.2; ESI-MS: m/z=226.9
[M+H]+; HR-MS-ESI: m/z=227.0561, calcd. for C11H15OS2
[M+H]+: 227.0559.
0.8 mLminÀ1, l=210 nm): tminor =11.4 min, tmajor =19.7 min;
[a]2D6: +79.5 (c 1.2, CHCl3); IR (KBr): n=3068, 2911, 1592,
1571, 1475, 1038, 872, 694 cmÀ1 1H NMR (300 MHz,
;
(+)-trans-2-(4’-Isopropylphenyl)-1,3-dithiane 1-oxide (5e):
White solid; yield: 87%; >99:1 dr, 78:22 er; mp 105–1078C;
HPLC (Chiralpak OD-H, hexane/i-PrOH=70/30, flow rate:
1.0 mLminÀ1, l=230 nm): tminor =7.7 min, tmajor =15.4 min;
[a]2D6: +78.4 (c 1.1, CHCl3); IR (KBr): n=2957, 1508, 1033,
CDCl3): d=7.72–7.00 (m, 4H), 4.53 (s, 1H), 3.63–3.49 (m,
1H), 2.93–2.63 (m, 3H), 2.58–2.26 (m, 2H); 13C NMR
(75 MHz, CDCl3): d=135.2, 134.9, 130.3, 129.5, 128.7, 27.0,
68.9, 54.7, 31.3, 29.4; ESI-MS (%): m/z=246.8 (100) and
248.8 (41) [M+H]+ for 35Cl and 37Cl isotopic pattern; HR-
854 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=7.33 (d, J=
MS-ESI
(%):
m/z=247.0017
(100),
calcd.
for
C10H1235ClO32S2 [M+H]+: 247.0013 and m/z=248.9983 (41),
8.1 Hz, 2H), 7.25 (d, J=8.1 Hz, 2H), 4.54 (s, 1H), 3.58–3.50
(m, 1H), 2.96–2.80 (m, 2H), 2.74 (dt, J=13.2, 2.7 Hz, 1H),
2.68–2.60 (m, 1H), 2.53–2.44 (m, 1H), 2.40–2.27 (m, 1H),
1.23 (d, J=7.0 Hz, 6H); 13C NMR (100 MHz, CDCl3): d=
149.9, 130.4, 128.5, 127.1, 69.2, 54.6, 33.7, 31.3, 29.4, 23.7;
ESI-MS: m/z=254.9 [M+H]+; HR-MS-ESI: m/z=255.0874,
calcd. for C13H19OS2 [M+H]+: 255.0872.
calcd. for C10H1237ClO34S2 [M+H]+: 248.9989.
(+)-trans-2-(4’-Chlorophenyl)-1,3-dithiane 1-Oxide (5j):
White solid; yield: 99%; >99:1 dr, 85:15 er; mp 144–1468C;
HPLC (Chiralpak OD-H, hexane/i-PrOH=70/30, flow rate:
1.0 mLminÀ1, l=230 nm): tminor =10.0 min, tmajor =22.9 min;
[a]2D6: +97.7 (c 1.2, CHCl3); IR (KBr): n=3075, 2924, 1490,
1
1406, 1045, 853, 764 cmÀ1; H NMR (300 MHz, CDCl3): d=
(+)-trans-2-(2’-Fluorophenyl)-1,3-dithiane 1-oxide (5f):
White solid; yield: 76%; 93:7 dr, 80:20 er; mp 117–1188C;
HPLC (Chiralpak OD-H, hexane/i-PrOH=70/30, flow rate:
1.0 mLminÀ1, l=210 nm): tminor =9.6 min, tmajor =18.9 min;
[a]2D6: +88.5 (c 0.87, CHCl3); IR (KBr): n=3075, 2912, 1490,
7.41–7.32 (m, 4H), 4.53 (s, 1H), 3.62–3.53 (m, 1H), 2.94–
2.65 (m, 3H), 2.58–2.47 (m, 1H), 2.44–2.28 (m, 1H);
13C NMR (75 MHz, CDCl3): d=135.3, 131.8, 130.0, 129.3,
68.8, 54.7, 31.3, 29.4; ESI-MS (%): m/z=246.8 (100) and
248.8 (41) [M+H]+ for 35Cl and 37Cl isotopic pattern; HR-
1
1233, 1040, 759 cmÀ1; H NMR (400 MHz, CDCl3): d=7.61–
7.40 (m, 1H), 7.38–7.27 (m, 1H), 7.25–7.15 (m, 1H), 7.15–
7.05 (m, 1H), 5.03 (s, 1H), 3.64–3.51 (m, 1H), 2.97–2.87 (m,
1H), 2.82 (dt, J=13.2, 2.6 Hz, 1H), 2.73–2.60 (m, 1H), 2.57–
2.46 (m, 1H), 2.43–2.29 (m, 1H); 13C NMR (75 MHz,
CDCl3): d=160.8 (d, JC,F =248.3 Hz), 130.7 (d, JC,F =8.3 Hz),
129.1 (d, JC,F =1.5 Hz), 124.9 (d, JC,F =3.0 Hz), 120.9 (d,
MS-ESI
(%):
m/z=247.0010
(100),
calcd.
for
C10H1235ClO32S2 [M+H]+: 247.0013 and m/z=248.9983 (41),
calcd. for C10H1237ClO34S2 [M+H]+: 248.9989.
(+)-trans-2-(4’-Bromophenyl)-1,3-dithiane 1-oxide (5k):
White solid; yield: 98%; >99:1 dr, 85:15 er; mp 163–1658C;
HPLC (Chiralpak OD-H, hexane/i-PrOH=70/30, flow rate:
1.0 mLminÀ1, l=254 nm: tminor =10.5 min, tmajor =23.7 min;
[a]2D6: +87.6 (c 1.2, CHCl3); IR (KBr): n=3060, 2922, 1487,
J
C,F =14.3 Hz), 115.9 (d, JC,F =21.8 Hz), 61.6, 54.8, 31.4, 29.6;
ESI-MS: m/z=230.9 [M+H]+; HR-MS-ESI: m/z=231.0314,
calcd. for C10H12FOS2 [M+H]+: 231.0308.
1
1402, 1040, 851 cmÀ1; H NMR (300 MHz, CDCl3): d=7.53
(+)-trans-2-(4’-Fluorophenyl)-1,3-dithiane 1-oxide (5g):
White solid; yield: 98%; 98:2 dr, 84:16 er; mp 126–1278C;
HPLC (Chiralpak OD-H, hexane/i-PrOH=70/30, flow rate:
1.0 mLminÀ1, l=254 nm): tminor =9.2 min. tmajor =21.2 min;
[a]2D6: +71.4 (c 0.94, CHCl3); IR (KBr): n=3056, 2914, 1599,
(d, J=8.3 Hz, 2H), 7.29 (d, J=8.3 Hz, 2H), 4.52 (s, 1H),
3.62–3.49 (m, 1H), 2.93–2.62 (m, 3H), 2.57–2.45 (m, 1H),
2.44–2.25 (m, 1H); 13C NMR (75 MHz, CDCl3): d=132.3,
132.1, 130.2, 123.5, 68.8, 54.6, 31.2, 29.4; ESI-MS (%): m/z=
290.7 (94) and 292.7 (100) [M+H]+ for 79Br and 81Br isotop-
ic pattern; HR-MS-ESI (%): m/z=290.9510 (94), calcd. for
C10H1279BrO32S2 [M+H]+: 290.9507 and m/z=292.9488
(100), calcd. for C10H1281BrO34S2 [M+H]+: 292.9486.
1
1509, 1224, 1038, 850 cmÀ1; H NMR (300 MHz, CDCl3): d=
7.47–7.35 (m, 2H), 7.16–7.03 (m, 2H), 4.54 (s, 1H), 3.63–
3.50 (m, 1H), 2.94–2.83 (m, 1H), 2.81–2.63 (m, 2H), 2.59–
2.47 (m, 1H), 2.45–2.27 (m, 1H); 13C NMR (75 MHz,
CDCl3): d=163.1 (d, JC,F =247.5 Hz), 130.5 (d, JC,F =8.3 Hz),
129.2 (d, JC,F =3.0 Hz), 116.1 (d, JC,F =21.8 Hz), 68.7, 54.7,
31.4, 29.4; ESI-MS: m/z=230.9 [M+H]+; HRMS-ESI: m/
z=231.0304, calcd. for C10H12FOS2 [M+H]+: 231.0308.
(+)-trans-2-(2’-Chlorophenyl)-1,3-dithiane 1-oxide (5h):
White solid; yield: 95%; 90:10 dr, 81:19 er; mp 134–1368C;
HPLC (Chiralpak OD-H, hexane/i-PrOH=70/30, flow rate:
0.8 mLminÀ1, l=210 nm): tminor =12.1 min, tmajor =17.4 min;
[a]2D6: +78.3 (c 1.1, CHCl3); IR (KBr): n=3060, 2916, 1474,
(+)-trans-2-(3’-Nitrophenyl)-1,3-dithiane 1-oxide (5l):
White solid; yield: 94%; >99:1 dr, 87:13 er; mp 153–1558C;
HPLC (Chiralpak OD-H, hexane/i-PrOH=70/30, flow rate:
0.8 mLminÀ1, l=254 nm): tminor =19.2 min, tmajor =31.0 min;
[a]2D6: +70.7 (c 1.0, CHCl3); IR (KBr): n=3064, 2916, 1531,
1
1352, 1037, 692 cmÀ1; H NMR (300 MHz, CDCl3): d=8.40–
8.15 (m, 2H), 7.77 (d, J=7.7 Hz, 1H), 7.61 (t, J=8.0 Hz,
1H), 4.70 (s, 1H), 3.69–3.56 (m, 1H), 3.03–2.68 (m, 3H),
2.65–2.52 (m, 1H), 2.51–2.32 (m, 1H); 13C NMR (75 MHz,
CDCl3): d=148.4, 135.5, 134.9, 130.1, 124.2, 123.8, 68.5, 54.7,
31.2, 29.4; ESI-MS: m/z=257.8 [M+H]+; HR-MS-ESI: m/
z=258.0254, calcd. for C10H12NO3S2 [M+H]+: 258.0253.
(+)-trans-2-(4’-Nitrophenyl)-1,3-dithiane 1-oxide (5m):
White solid; yield: 79%; >99:1 dr, 83:17 er; mp 162–
1638C;HPLC (Chiralpak OD-H, hexane/i-PrOH=70/30,
1
1427, 1032, 753 cmÀ1; H NMR (300 MHz, CDCl3): d=7.63–
7.48 (m, 1H), 7.48–7.39 (m, 1H), 7.39–7.22 (m, 2H), 5.28 (s,
1H), 3.67–3.52 (m, 1H), 3.04–2.76 (m, 2H), 2.71–2.60 (m,
1H), 2.60–2.47 (m, 1H), 2.46–2.27 (m, 1H); 13C NMR
(75 MHz, CDCl3): d=134.9, 131.4, 130.1, 130.0, 129.1, 127.7,
65.1, 54.8, 31.6, 29.7; ESI-MS (%): m/z=246.8 (100) and
248.8 (41) [M+H]+ for 35Cl and 37Cl isotopic pattern; HR-
flow rate: 1.0 mLminÀ1, l=254 nm): tminor =19.4 min, tmajor
37.5 min; [a]2D6: +121.4 (c 0.92, CHCl3); IR (KBr): n=3130,
2935, 1604, 1526, 1354, 1041, 867, 695 cmÀ1 1H NMR
=
MS-ESI
(%):
m/z=247.0013
(100),
calcd.
for
C10H1235ClO32S2 [M+H]+: 247.0013 and m/z=248.9987 (41),
;
calcd. for C10H1237ClO34S2 [M+H]+: 248.9989.
(300 MHz, CDCl3): d=8.26 (d, J=8.6 Hz, 2H), 7.61 (d, J=
8.6 Hz, 2H), 4.68 (s, 1H), 3.68–3.56 (m, 1H), 3.00–2.70 (m,
3H), 2.64–2.52 (m, 1H), 2.51–2.32 (m, 1H); 13C NMR
(75 MHz, CDCl3): d=148.2, 140.5, 129.8, 124.1, 68.7, 54.8,
(+)-trans-2-(3’-Chlorophenyl)-1,3-dithiane 1-oxide (5i):
White solid; yield: 99%; >99:1 dr, 82:18 er; mp 118–1198C;
HPLC (Chiralpak OD-H, hexane/-iPrOH=70/30, flow rate:
Adv. Synth. Catal. 2012, 354, 1012 – 1022
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1019

Zhao-Min Liu et al.
FULL PAPERS
31.2, 29.4; ESI-MS: m/z=257.8 [M+H]+; HR-MS-ESI: m/
z=258.0253, calcd. for C10H12NO3S2 [M+H]+: 258.0253.
(+)-trans-2-(4’-Cyanophenyl)-1,3-dithiane 1-oxide (5n):
White solid; yield: 75%; >99:1 dr, 85:15 er; mp 137–1388C;
HPLC (Chiralpak OD-H, hexane/i-PrOH=70/30, flow rate:
1.0 mLminÀ1, l=254 nm): tminor =16.4 min, tmajor =37.1 min;
[a]2D6: +130.9 (c 0.82, CHCl3); IR (KBr): n=3095, 2904,
8.07–7.71 (m, 4H), 7.67–7.37 (m, 3H), 4.72 (s, 1H), 3.63–
3.50 (m, 1H), 2.95–2.61 (m, 3H), 2.56–2.29 (m, 2H);
13C NMR (75 MHz, CDCl3): d=133.6, 133.2, 130.6, 129.0,
128.6, 128.1, 127.7, 126.7, 126.5, 125.5, 69.9, 54.7, 31.4, 29.5;
ESI-MS: m/z=262.9 [M+H]+; HR-MS-ESI: m/z=263.0562,
calcd. for C14H15OS2 [M+H]+: 263.0559.
(+)-trans-2-(2’-Thiophenyl)-1,3-dithiane 1-oxide (5s):
White solid; yield: 98%; 98:2 dr, 81:19 er; mp 125–1278C;
HPLC (Chiralpak OD-H, hexane/i-PrOH=70/30, flow rate:
1.0 mLminÀ1, l=254 nm): tminor =11.2 min, tmajor =26.9 min;
[a]2D6: +65.1 (c 1.1, CHCl3); IR (KBr): n=3081, 2913, 1035,
1
2230, 1038, 861 cmÀ1; H NMR (300 MHz, CDCl3): d=7.70
(d, J=8.3 Hz, 2H), 7.54 (d, J=8.2 Hz, 2H), 4.62 (s, 1H),
3.66–3.53 (m, 1H), 2.98–2.68 (m, 3H), 2.62–2.49 (m, 1H),
2.48–2.30 (m, 1H); 13C NMR (75 MHz, CDCl3): d=138.5,
132.6, 129.5, 118.1, 112.9, 68.9, 54.7, 31.1, 29.3; ESI-MS: m/
z=237.9 [M+H]+; HR-MS-ESI: m/z=238.0346, calcd. for
C11H12NOS2 [M+H]+: 238.0355.
746 cmÀ1 1H NMR (300 MHz, CDCl3): d=7.41–7.32 (m,
;
1H), 7.26–7.18 (m, 1H), 7.09–6.98 (m, 1H), 4.85 (s, 1H),
3.55–3.44 (m, 1H), 2.94–2.64 (m, 3H), 2.59–2.46 (m, 1H),
2.42–2.25 (m, 1H); 13C NMR (75 MHz, CDCl3): d=134.9,
128.1, 127.3, 127.1, 64.3, 54.0, 31.4, 28.5; ESI-MS: m/z=
218.9 [M+H]+; HR-MS-ESI: m/z=218.9963, calcd. for
C8H11OS3 [M+H]+: 218.9967.
(+)-trans-2-[4’-(Trifluoromethyl)phenyl]-1,3-dithiane
1-
oxide (5o): White solid; yield: 93%; >99:1 dr, 85:15 er; mp
99–1008C; HPLC (Chiralpak OD-H, hexane/i-PrOH=70/
30, flow rate: 1.0 mLminÀ1, l=210 nm): tminor =8.8 min,
t
major =21.3 min; [a]2D6: +74.5 (c 1.0, CHCl3); IR (KBr): n=
1
2937, 1326, 1129, 1068, 1038, 861 cmÀ1; H NMR (300 MHz,
CDCl3): d=7.67 (d, J=8.2 Hz, 2H), 7.55 (d, J=8.2 Hz, 2H),
4.62 (s, 1H), 3.66–3.53 (m, 1H), 2.96–2.67 (m, 3H), 2.61–
2.27 (m, 2H); 13C NMR (100 MHz, CDCl3): d=137.3, 130.7
(q, JC,F =32.0 Hz), 128.9, 125.6 (d, JC,F =4.0 Hz), 123.4 (q,
Acknowledgements
We are grateful for financial support of the National Natural
Science Foundation of China (20772113, 21072145), Founda-
tion for the Author of National Excellent Doctoral Disserta-
tion of P.R. China (200931), and Natural Science Foundation
of Jiangsu Province of China (BK2009115). This project was
funded by the Priority Academic Program Development of
Jiangsu Higher Education Institutions (PAPD).
J
C,F =271.0 Hz), 69.0, 54.7, 31.2, 29.4; ESI-MS: m/z=280.8
[M+H]+;
HR-MS-ESI:
m/z=281.0279,
calcd.
for
C11H12F3OS2 [M+H]+: 281.0276.
(+)-trans-2-(2’,4’-Dichlorophenyl)-1,3-dithiane
1-oxide
(5p): White solid; yield: 60%; 88:12 dr, 79:21 er; mp 177–
1798C; HPLC (Chiralpak OD-H, hexane/i-PrOH=70/30,
flow rate: 1.0 mLminÀ1, l=230 nm): tminor =10.0 min, tmajor
=
16.3 min; [a]2D6: +83.8 (c 0.89, CHCl3); IR (KBr): n=3074,
1
2931, 1582, 1470, 1056, 869, 782 cmÀ1; H NMR (300 MHz,
References
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1H), 2.60–2.46 (m, 1H), 2.45–2.26 (m, 1H); 13C NMR
(75 MHz, CDCl3): d=135.6, 135.3, 130.2, 130.0, 129.8, 128.0,
64.5, 54.7, 31.5, 29.5; ESI-MS (%): m/z=280.7 (100) and
282.7 (74) [M+H]+ for 35Cl and 37Cl isotopic pattern; HR-
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1423, 1038, 783 cmÀ1; H NMR (400 MHz, CDCl3): d=8.29
(d, J=8.1 Hz, 1H), 7.94–7.77 (m, 2H), 7.71 (d, J=7.1 Hz,
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1.0 mLminÀ1, l=254 nm): tminor =14.2 min, tmajor =18.1 min;
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1507, 1035, 826, 759 cmÀ1; H NMR (300 MHz, CDCl3): d=
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Adv. Synth. Catal. 2012, 354, 1012 – 1022
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asc.wiley-vch.de
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Adv. Synth. Catal. 2012, 354, 1012 – 1022