Hypervalent Iodine(V)-Induced Asymmetric Oxidation of Sulfides to Sulfoxides Mediated by Reversed Micelles: Novel Nonmetallic Catalytic System

Article abstract of DOI:10.1021/jo982295t

Although several types of chiral hypervalent iodine reagents have been used for asymmetric induction, all of them have needed more than a stoichiometric amount of chiral reagents and have shown low enantioselectivities. The described new catalytic asymmetric oxidation using a hypervalent iodine(V) reagent, iodoxybenzene (PhIO₂), in a cationic reversed micellar system provides the first example of a catalytic asymmetric oxidation of sulfides to sulfoxides in high chemical yield with moderate to good enantioselectivity without the use of any transition-metal catalysts. The solubilization and activation of PhIO₂ by adding catalytic amounts of both cetyltrimethylammonium bromide (CTAB) and a chiral tartaric acid derivative were found to be indispensable for the enhancement of chemical and optical yields.

Full text of DOI:10.1021/jo982295t

J . Org. Chem. 1999, 64, 3519-3523
3519
Hyp er va len t Iod in e(V)-In d u ced Asym m etr ic Oxid a tion of Su lfid es
to Su lfoxid es Med ia ted by Rever sed Micelles: Novel Non m eta llic
Ca ta lytic System
Hirofumi Tohma, Shinobu Takizawa, Hiroaki Watanabe, Yuko Fukuoka,
Tomohiro Maegawa, and Yasuyuki Kita*
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka,
Suita, Osaka 565-0871, J apan
Received November 19, 1998
Although several types of chiral hypervalent iodine reagents have been used for asymmetric
induction, all of them have needed more than a stoichiometric amount of chiral reagents and have
shown low enantioselectivities. The described new catalytic asymmetric oxidation using a
hypervalent iodine(V) reagent, iodoxybenzene (PhIO2), in a cationic reversed micellar system
provides the first example of a catalytic asymmetric oxidation of sulfides to sulfoxides in high
chemical yield with moderate to good enantioselectivity without the use of any transition-metal
catalysts. The solubilization and activation of PhIO2 by adding catalytic amounts of both
cetyltrimethylammonium bromide (CTAB) and a chiral tartaric acid derivative were found to be
indispensable for the enhancement of chemical and optical yields.
In tr od u ction
sulfoxides in micellar and reversed micellar systems
using iodosobenzene (PhIdO).5 We were therefore curious
whether placing PhIdO in an organized chiral surfactant
medium, such as a micelle, could oxidize sulfides to
sulfoxides stereoselectively. Several applications of mi-
cellar systems to stereoselective organic syntheses using
chiral surfactants have been reported.6 Among such
examples, asymmetric oxidation reactions, to our knowl-
edge, have only produced poor stereoselectivities (up to
15% ee).7 Accordingly, the use of chiral quaternary
ammonium salts such as N-[4-(trifluoromethyl)benzyl]-
cinchoninium bromide and (-)-cetyldimethylphenylethyl-
ammonium bromide instead of CTAB were not at all
effective for asymmetric induction in our recently devel-
oped micellar and reversed micellar systems.5 We have
Hypervalent iodine reagents have been extensively
used in organic syntheses due to their low toxicity, ready
availability, and easy handling.1 However, regarding
asymmetric induction, especially that of sulfides to sulf-
oxides, several types of hypervalent iodine reagents have
been examined with little success. These include reagents
coordinated by chiral ligands or a chiral host compound
such as carboxylic acids,2a,c,g sulfonic acids,2f,i alcohols,2d
binaphthyl group,2e ethers,2h,j,k and â-cyclodextrin.2b The
poor efficiency and practicality have been attributed to
their low enantioselectivities and the necessity of more
than a stoichiometric amount of chiral sources. As a
result, hypervalent iodine reagents have normally been
used merely as co-oxidants in transition-metal-catalyzed
asymmetric oxidation reactions.3 Therefore, the develop-
ment of catalytic and enantioselective hypervalent iodine-
induced oxidation of sulfides to sulfoxides has been an
important area of organosulfur chemistry.
(3) For the asymmetric oxidation of sulfides to sulfoxides, see: (a)
Groves, J . T.; Viski, P. J . Org. Chem. 1990, 55, 3628-3634. (b)
Halterman, R. L.; J an, S.-T.; Nimmons, H. L. Synlett 1991, 791-792.
(c) Chiang, L.-C.; Konishi, K.; Aida, T.; Inoue, S. J . Chem. Soc., Chem.
Commun. 1992, 254-256. (d) Naruta, Y.; Tani, F.; Maruyama, K.
Tetrahedron: Asymmetry 1991, 2, 533-542. (e) Noda, K.; Hosoya, N.;
Irie, R.; Yamashita, Y.; Katsuki, T. Tetrahedron 1994, 32, 9609-9618.
(f) Takada, H.; Nishibayashi, Y.; Ohe, K.; Uemura, S. Chem. Commun.
1996, 931-932. (g) Kokubo, C.; Katsuki, T. Tetrahedron 1996, 52,
13895-13900. (h) Baird, C. P.; Rayner, C. M. J . Chem. Soc., Perkin
Trans. 1 1998, 1973-2003 and references therein.
(4) (a) Tamura, Y.; Yakura, T.; Haruta, J .; Kita, Y. Tetrahedron Lett.
1985, 26, 3837-3840. (b) Tamura, Y.; Yakura, T.; Haruta, J .; Kita, Y.
J . Org. Chem. 1987, 52, 3927-3930. (c) Kita, Y.; Tohma, H.; Kikuchi,
K.; Inagaki, M.; Yakura, T. J . Org. Chem. 1991, 56, 435-438. (d) Kita,
Y.; Tohma, H.; Inagaki, M.; Hatanaka, K.; Yakura, T. J . Am. Chem.
Soc. 1992, 114, 2175-2180. (e) Kita, Y.; Tohma, H.; Hatanaka, K.;
Takada, T.; Fujita, S.; Mitoh, S.; Sakurai, H.; Oka, S. J . Am. Chem.
Soc. 1994, 116, 3684-3691. (f) Kita, Y.; Takada, T.; Mihara, S.; Whelan,
B. A.; Tohma, H. J . Org. Chem. 1995, 60, 7144-7148. (g) Kita, Y.;
Gyoten, M.; Ohtsubo, M.; Tohma, H.; Takada, T. Chem. Commun. 1996,
1481-1482. (h) Kita, Y.; Egi, M.; Okajima, A.; Ohtsubo, M.; Takada,
T.; Tohma, H. Chem. Commun. 1996, 1491-1492. (i) Kita, Y.; Egi, M.;
Ohtsubo, M.; Saiki, T.; Takada, T.; Tohma, H. Chem. Commun. 1996,
2225-2226. (j) Tohma, H.; Egi, M.; Ohtsubo, M.; Watanabe, H.;
Takizawa, S.; Kita, Y. Chem. Commun. 1998, 173-174. (k) Kita, Y.;
Watanabe, H.; Egi, M.; Saiki, T.; Fukuoka, Y.; Tohma, H. J . Chem.
Soc., Perkin Trans. 1 1998, 635-636. (l) Kita, Y.; Arisawa, M.; Gyoten,
M.; Nakajima, M.; Hamada, R.; Tohma, H.; Takada, T. J . Org. Chem.
1998, 63, 6625-6633. (m) Takada, T.; Arisawa, M.; Gyoten, M.;
Hamada, R.; Tohma, H.; Kita, Y. J . Org. Chem. 1998, 63, 7698-7706.
(5) Tohma, H.; Takizawa, S.; Watanabe, H.; Kita, Y. Tetrahedron
Lett. 1998, 39, 4547-4550.
As a continuation of our studies on hypervalent iodine
chemistry,4 we recently reported quaternary ammonium
salt catalyzed oxidation of sulfides to the corresponding
(1) For reviews, see: (a) Ochiai, M. Rev. Heteroatom Chem. 1989,
2, 92-111. (b) Moriarty, R. M.; Vaid, R. K. Synthesis 1990, 431-447.
(c) Moriarty, R. M.; Vaid, R. K.; Koser, G. F. Synlett 1990, 365-383.
(d) Varvoglis, A. The Organic Chemistry of Polycoordinated Iodine;
VCH Publishers Inc.: New York, 1992. (e) Kita, Y.; Tohma, H.; Yakura,
T. Trends Org. Chem. 1992, 3, 113-128. (f) Stang, P. J .; Zhdankin, V.
V. Chem. Rev. 1996, 96, 1123-1178. (g) Varvoglis, A. Hypervalent
Iodine in Organic Synthesis; Academic Press: San Diego, 1997. (h)
Kitamura, T.; Fujiwara, Y. Org. Prep. Proc. Int. 1997, 29, 409-458.
(2) (a) Merkushev, E. B.; Novikov, A. N.; Makarchenko, S. S.;
Moskal’chuk, A. S.; Glushkova, V. V.; Kogai, I.; Polyakova, L. G. J .
Org. Chem. USSR (Engl. Transl.) 1975, 11, 1246-1249. (b) Czarnik,
A. W. J . Org. Chem. 1984, 49, 924-927. (c) Imamoto, T.; Koto, H.
Chem. Lett. 1986, 967-968. (d) Ray, D. G., III; Koser, G. F. J . Am.
Chem. Soc. 1990, 112, 5672-5673. (e) Ochiai, M.; Takaoka, Y.; Masaki,
Y.; Nagao, Y.; Shiro, M. J . Am. Chem. Soc. 1990, 112, 5677-5678. (f)
Hatzigrigoriou, E.; Varvoglis, A.; Bakola-Christianopoulou, M. J . Org.
Chem. 1990, 55, 315-318. (g) Ray, D. G., III; Koser, G. F. J . Org. Chem.
1992, 57, 1607-1610. (h) Rabah, G. A.; Koser, G. F. Tetrahedron Lett.
1996, 37, 6453-6456. (i) Xia, M.; Chen, Z.-C. Synth. Commun. 1997,
27, 1315-1320. (j) Wirth, T.; Hirt, U. H. Tetrahedron: Asymmetry
1997, 8, 23-26. (k) Hirt, U. H.; Spingler, B.; Wirth, T. J . Org. Chem.
1998, 63, 7674-7679.
10.1021/jo982295t CCC: $18.00 © 1999 American Chemical Society
Published on Web 04/24/1999

3520 J . Org. Chem., Vol. 64, No. 10, 1999
Tohma et al.
Ta ble 1
made subsequent improvements on this micellar system
and now report a novel nonmetallic asymmetric oxidation
reaction of sulfides to sulfoxides devoid of overoxidation
to sulfones with moderate to good enantioselectivities (up
to 72% ee)8 using a hypervalent iodine(V) reagent,
iodoxybenzene9 (PhIO2) (0.5 equiv), in toluene in the
presence of catalytic amounts of cetyltrimethylammo-
nium bromide (CTAB), water, and readily available chiral
diacyltartaric acid (3) (eq 1).
Resu lts a n d Discu ssion
First, we examined whether a chiral additive could
induce enantioselective oxidation of sulfides in our mi-
cellar systems. We found that in the presence of 10 mol
% of dibenzoyl-D-tartaric acid (3a ) and 20 mol % of CTAB
(achiral quaternary ammonium salt) oxidation of methyl
p-tolyl sulfide (1a ) to methyl p-tolyl sulfoxide (2a ) by
PhIdO in 60:1 toluene-H2O proceeds in 80% yield with
30% ee. Hence, the next step was to enhance the enantio-
selectivity by altering oxidants, water content, and chiral
sources.
Ta ble 2. Effect of Wa ter Con ten t in Asym m etr ic
Oxid a tion of 1a to 2a
We examined the asymmetric oxidation in CTAB
reversed micelles using a variety of oxidants. Table 1
shows that among the hypervalent iodine reagents, 0.5
equiv of PhIO2 was most effective for the asymmetric
oxidation of 1a .10 Increasing the amount of PhIO2 did not
affect enantioselectivity at all but accelerated the reaction
without yielding the corresponding sulfone (entries 3 and
4; Table 1). Similarly, increasing the equivalencies of
CTAB and 3a accelerated the reaction, but did not
enhance its enantioselectivity.11
entry toluene/H2O (v/v) [H2O]/[CTAB] time (h) yield ee (%)
1
2
3
4
5
6
7
in toluene
0
14
70
140
280
24
6
2
2
4
trace
quant
quant
quant
quant
87
600
120
60
30
1
26
37
42
30
17
12
12
18
in H2O
85
a
[CTAB]; 6.55 × 10-3 M.
7-9; Table 1). In all cases, in the absence of CTAB the
reaction did not proceed at all, indicating that the forma-
tion of the micellar system is essential for the sulfoxi-
dation.
In contrast to iodine(III) or (V) reagents, other oxidants
such as H2O2, cumene hydroperoxide, and sodium hypo-
chlorite gave only poor enantiomeric excesses (entries
In reversed micelles, the water content that defines mi-
celle size plays an important role both in reactivity and
in enantioselectivity. The best optical yield (42% ee) of
2a was obtained in toluene-H2O (60:1) (entry 4; Table
2), while the reaction yielded only a trace amount of 2a
in the absence of water. As water content exceeds the
optimum amount, it becomes more difficult to form rigid
reversed micelles and CTAB works merely as a phase-
transfer catalyst. Therefore, in such cases (entries 5, 6;
Table 2) both the reaction rate and the enantioselectivity
decreased. Although CTAB can also form micelles in wa-
ter, water micelles generally form structurally less rigid
assemblies than that of reversed micelles. Thus, 2a was
obtained in 85% yield with only 12% ee (entry 7; Table 2).
Next, we optimized the chiral sources in the reaction.
The best chemical and optical yields were obtained by
the use of 10 mol % of di(2-MeO)benzoyl-L-tartaric acid
(3b) (quant, 53% ee) (entry 9; Table 3). The use of other
tartaric acid derivatives or chiral sources such as various
carboxylic acids, a sulfonic acid, an N-protected amino
acid, and a phosphonic acid did not improve the % ee of
2a .
(6) (a) Tascioglu, S. Tetrahedron 1996, 52, 11113-11152. (b) Zhang,
Y.-M.; Sun, P.-P. Tetrahedron: Asymmetry 1996, 7, 3055-3058. (c)
Zhang, Y.-M.; Wu, W. Ibid. 1997, 8, 2723-2725; 3575-3578. (d) Sun,
P.-P.; Zhang, Y.-M. Synth. Commun. 1997, 27, 4173-4179.
(7) Zhang, Y.-M.; Fu, C.-L.; Fan, W.-Q. Chin. J . Chem. 1990, 1, 89-
96 and references therein.
(8) Almost all highly enantioselective chemical oxidations of sulfides
to sulfoxides reported so far have required more than stoichiometric
amounts of chiral sources (or chiral oxidants) except for transition-
metal-catalyzed reactions. Only chiral hydroperoxyflavin-mediated
oxidation of sulfides achieved moderate enantioselectivities using a
catalytic amount of chiral source: Shinkai, S.; Yamaguchi, T.; Manabe,
O.; Toda, F. J . Chem. Soc., Chem. Commun. 1988, 1399-1401. For a
review, see: Kagan, H. B. Asymmetric Oxidation of Sulfides. In
Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH: New York, 1993;
pp 203-226 and references therein.
(9) (a) Formo, M. W.; J ohnson, J . R. Organic Syntheses; Wiley: New
York, 1955; Collect. Vol. III, pp 486-487. (b) Barton, D. H. R.; Godfrey,
C. R. A.; Morzycki, J . W.; Motherwell, W. B.; Ley, S. V. J . Chem. Soc.,
Perkin Trans. 1 1982, 1947-1952.
(10) The optical yield of the present reaction is remarkably affected
by the choice of solvent. That is, better optical yields were observed
with reversed micellar systems in nonpolar solvents (toluene: quant,
42% ee; n-hexane: quant, 37% ee; CCl4: 97%, 34% ee) than with
micelles in polar solvents (CHCl3: quant, 0% ee; CH2Cl2: quant, 0%
ee; MeCN: 88%, 1% ee; AcOEt: quant, 0% ee; acetone: trace) in the
presence of 3a (10 mol %), CTAB (20 mol %), and H2O.
(11) No enhancement of ee of 2a was observed when using various
ratios and amounts of CTAB and 3a . The ee of 2a were 42% ee (CTAB/
3a ) 2; [3a ] ) 10 mol %), 35% ee (CTAB/3a ) 1; [3a ] ) 10 mol %),
15% ee (CTAB/3a ) 0.5; [3a ] ) 40 mol %), and 41% ee (CTAB/3a ) 2;
[3a ] ) 100 mol %).
The present reaction is applicable to several sulfides
(1a -i) and provides corresponding sulfoxides in nearly

Asymmetric Oxidation of Sulfides to Sulfoxides
J . Org. Chem., Vol. 64, No. 10, 1999 3521
Ta ble 3. Asym m etr ic Oxid a tion of 1a to 2a Usin g
Va r iou s Ch ir a l Sou r ces
0.5 equiv of PhIO2 (from 34% ee at 6% conversion to 72%
ee at 95% conversion), while the % ee of 2b stays nearly
constant (38-48% ee) when using 1.0 equiv of PhIdO.
In these cases, the kinetic resolution of 2b cannot occur
since the corresponding sulfone does not form at all.12
Furthermore, the equivalency (either 0.5 equiv or 1.0
equiv) of PhIO2 neither affected the yield nor the % ee of
2b but did affect the reaction rate (Figure 1a,b). In
addition, the oxidation of 1b by PhIO2 did not proceed
at all without 3b, while a 42% yield of 2b was obtained
after 70 min when using PhIdO even in the absence of
3b (Figure 1d). The rate calculated from 10% consump-
tion of reactant 1b showed that the reaction rate without
3b is ca. 15% of the rate observed with 3b. Therefore,
correcting for this background reaction from the reaction
described in Figure 1d, the reaction pathway involving
3b is expected to yield ca. 56% ee (Figure 1c,d). Thus,
the higher enantioselectivity observed when using 0.5
equiv of PhIO2 (72% ee) rather than 1.0 equiv of PhIdO
(48% ee) seems to be partly caused by the unreactive
nature of PhIO2 in the absence of 3b. These results
suggest that there are other mechanistic reasons for the
higher enantioselectivity when using 0.5 equiv of PhIO2.
Since the oxidant and 3b might also be epimerizing the
sulfoxide center, we examined the stability of an enan-
tiomerically pure sulfoxide 2b under the reaction condi-
tions [the oxidant (1:1 PhIdO and PhIO2), which seems
to be generated in situ, 10 mol % 3b, and 20 mol % CTAB
in toluene-H2O (60:1)]. However, no change in the % ee
was observed even after 2 days when using racemic
sulfoxide 2b as well as enantiomerically pure sulfoxide
2b. This reaction does not seem to proceed via the simple
mechanism of sequential reduction of PhI(V)O2 to PhI-
(III)dO and then to PhI(I),13 but via the in situ formation
of some type of stereo-controlled reactive intermediate.
Although we cannot clearly identify the reactive inter-
mediate at this point, it may be an unprecedented
reagent formed from PhIO2, PhIdO, and the chiral
tartaric acid 3b.14 As the reaction proceeds, the formed
sulfoxide may perhaps be involved as well.
Ta ble 4. Ca ta lytic Asym m etr ic Oxid a tion of 1 to 2
To summarize, the likely explanation of the successful
catalytic asymmetric induction in our newly developed
metal-free system is thought to be the following: (i) the
in situ formation of stereocontrolled reactive species (the
remarkable enhancement of the % ee of 2b during the
course of the reaction (Figure 1a,b)), (ii) the high coor-
dination ability of the iodine(V) center similar to that of
transition metal species (the best result (entry 9; Table
3) was derived from the putative coordination of the MeO
group of 3b to the iodine center; other noncoordinating
oxidants gave only poor enantiomeric excesses), (iii)
quantitative yields with moderate to good enantiomeric
excesses when using 3b as a chiral source (Table 4). As
expected, similar optical yields were observed in the
presence of either 1 mol %, 50 mol %, or 100 mol % of
3b, although the reaction took longer to complete when
small amounts of CTAB (6.55 × 10-3 M) were used
(entries 2-5; Table 4).
Further kinetic study using methyl p-nitrophenyl
sulfide (1b) as a model substrate yielded some informa-
tion on the mechanism of this system. Sulfide 1b was
chosen because it has the best % ee and its moderate
reaction rate allows easy detection of the change in % ee
of 2b as a function of reaction time. The results are shown
in Figure 1.
(12) Several groups reported that a kinetic resolution of the formed
sulfoxides to the corresponding sulfones enhances the % ee of the
sulfoxides effectively in asymmetric oxidation reactions of sulfides;
see: (a) Komatsu, N.; Hashizume, M.; Sugita, T.; Uemura, S. J . Org.
Chem. 1993, 58, 7624-7626. (b) Yamanoi, Y.; Imamoto, T. J . Org.
Chem. 1997, 62, 8560-8564. (c) Adam, W.; Korb, M. N.; Roschmann,
K. J .; Saha-Mo¨ller, C. R. J . Org. Chem. 1998, 63, 3423-3428 (d)
Palombi, L.; Bonadies, F.; Pazienza, A.; Scettri, A. Tetrahedron:
Asymmetry 1998, 9, 1817-1822 and references therein.
(13) If the sequential reduction of PhIO2 proceeds when using 0.5
equiv of PhIO2, the initial ee value should be maximum and then
decrease to the final ee. However, in this case, the enhancement of
enantioselectivity occurs during the course of the reaction regardless
of the equivalencies of PhIO2.
The initial reaction rate with 1.0 equiv of PhIdO is
approximately eight times faster than that with 0.5 equiv
of PhIO2 (Figure 1a,c). Interestingly, the % ee of 2b
increases during the course of the reaction when using
(14) To confirm this, we examined the asymmetric oxidation of 1b
using the mixture of 0.1 equiv of PhIdO and 0.45 equiv of PhIO2. As
a
result, no improvement of the final ee of 2b (69% ee at 98%
conversion) was observed, but the initial ee value increased (48% ee
at 5% conversion).

3522 J . Org. Chem., Vol. 64, No. 10, 1999
Tohma et al.
F igu r e 1. Asymmetric oxidation of sulfide 1b as a function of reaction time (10 mol % 3b; 20 mol % CTAB; toluene-H2O (60:1))
[yields and ee were determined by HPLC analysis of the crude reaction mixture on a chiral column (Daicel Chiralpak AD).]
reversed micellar effects which promote solubilization of
PhIO2 and provide well-defined reaction sites, and (iv)
the extremely low reactivity of PhIO2 in the absence of
chiral activator 3b. Although PhIO2 has been used
infrequently in organic synthesis1 due to its insolubility
in H2O and various organic solvents, we achieved the
asymmetric oxidation of sulfides in greater efficiency
than with PhIdO by exploiting exactly this property of
PhIO2, that is, its selective solubility.
clarification of the mechanism for the present asymmetric
induction are now underway.
Exp er im en ta l Section
1H NMR (and 13C NMR) spectra were recorded in CDCl3,
unless otherwise noted, with TMS or CHCl3 as an internal
standard. Infrared (IR) absorption spectra were recorded as a
KBr pellet. Iodosobenzene was purchased from Tokyo Chemi-
cal Industry Co., Ltd. (TCI). Iodoxybenzene was prepared
according to literature procedure.9 Sulfides (1a , 1b, 1e) were
purchased from Aldrich. Sulfides (1c, d , f-h ) were prepared
from the corresponding thiophenols by alkylation with DBU
and iodomethane or iodoethane.15a Sulfide 1i was obtained by
sodium reduction of benzothiophene.15b Yields refer to the
average of at least two isolated yields. Yields of g99% were
considered quantitative. All the enantiomeric excesses (ee) of
Con clu sion s
We accomplished an unprecedented catalytic asym-
metric oxidation reaction of sulfides to sulfoxides using
a still underexplored hypervalent iodine(V) reagent,
PhIO2, in high chemical yield with moderate to good
enantiomeric excess in the presence of a catalytic amount
of readily available 3b. The application of this reversed
micellar system to other stereoselective reactions and the
(15) (a) Ono, N.; Miyake, H.; Saito, T.; Kaji, A. Synthesis 1980, 952-
953. (b) Birch, S.; Dean, R.; Whitehead, E. J . Inst. Petroleum. 1954,
40, 76-85.

Asymmetric Oxidation of Sulfides to Sulfoxides
J . Org. Chem., Vol. 64, No. 10, 1999 3523
2a -i were measured by chiral HPLC analysis: Daicel Chiral-
pak AD, Chiralcel OD, and Chiralcel OJ columns using a UV/
vis detector or a multiwavelength detector.
Di(2-m eth oxy)ben zoyl-L-ta r ta r ic Acid (3b). Chiral dia-
cyltartaric acids were easily prepared in a manner similar to
Yamamoto’s method16 in good yields.
(d, 2H, J ) 8.7 Hz); 13C NMR δ 43.8, 124.4, 124.6, 149.3, 153.1.
Daicel Chiralpak AD column at λ ) 287 nm, n-hexane/2-propa-
nol (94:6) as eluent and a flow rate of 1.0 mL/min: tR (S) )
48.7 min, tR (R) ) 56.8 min, ee ) 72%; [R]25D -112.4 (c ) 1.32,
CHCl3) (lit.17c ((R)-2b; 99.3% ee); [R]D +156.9 (c ) 0.75, CHCl3)).
(S)-Meth yl 3-n itr op h en yl su lfoxid e (2c): a colorless
1
P r ep a r a tion of 3b. To a stirred suspension of dibenzyl-L-
tartarate (200 mg, 0.606 mmol) and 2-methoxybenzoic acid
(313 mg, 2.06 mmol) in benzene (4 mL) was added dropwise
trifluoroacetic anhydride (0.324 mL, 2.24 mmol) over 10 min
at room temperature and the mixture stirred for 1 h. To the
reaction mixture was added aqueous saturated NaHCO3 at 0
°C, and then the resulting mixture was extracted with Et2O.
The organic layer was washed with brine, dried over Na2SO4,
and evaporated. The residue was purified by column chroma-
tography (SiO2/n-hexane/Et2O/CH2Cl2 ) 6:1:5) to give dibenzyl-
L-di(2-methoxy)benzoyltartarate 3′b (362 mg, quant) as a
colorless oil.
crystal; H NMR δ 2.82 (s, 3H), 7.78 (t, 1H, J ) 7.9 Hz), 8.02
(d, 1H, J ) 7.7 Hz), 8.37 (d, 1H, J ) 7.7 Hz), 8.51 (s, 1H); 13
NMR δ 44.0, 118.9, 125.7, 129.2, 130.6, 148.6, 148.7.
C
Daicel Chiralcel OJ column at λ ) 243 nm, n-hexane/2-pro-
panol (9:1) as eluent and a flow rate of 1.0 mL/min: tR (R) )
52.6 min, tR (S) ) 59.3 min, ee ) 64%; [R]25 -98.2 (c ) 0.85,
D
CHCl3). Although the ee value of the literature3d was deter-
mined by 1H NMR using a chiral shift reagent, we determined
the ee value of 2c by HPLC analysis. (In our case, 71% ee
was observed by NMR study as described in the litera-
ture.3d
)
(S)-Eth yl 4-n itr op h en yl su lfoxid e (2d ): a colorless crys-
tal; 1H NMR δ 1.17 (t, 3H, J ) 7.5 Hz), 2.69-2.76 (m, 1H),
2.93-2.99 (m, 1H), 7.73 (d, 2H, J ) 8.9 Hz), 8.32 (d, 2H, J )
8.9 Hz); 13C NMR δ 5.6, 50.1, 124.2, 125.2, 149.4, 150.9. Daicel
Chiralcel OD column at λ ) 291 nm, n-hexane/2-propanol (9:
1) as eluent and a flow rate of 0.5 mL/min: tR (R) ) 48.9 min,
3′b: 1H NMR δ 3.81 (s, 6H), 5.14 (s, 4H), 6.00 (s, 2H), 6.85-
6.93 (m, 4H), 7.12-7.22 (m, 10H), 7.45 (t, 2H, J ) 7.9 Hz),
7.78 (d, 2H, J ) 7.7 Hz); 13C NMR δ 55.8, 67.6, 71.1, 111.8,
117.7, 119.9, 128.0, 128.1, 128.2, 132.3, 134.2, 134.6, 159.8,
163.8, 165.5; IR (KBr) 1775, 1740, 1715, 1600 cm-1; [R]25
)
D
tR (S) ) 52.0 min, ee ) 57%; [R]25 -107.5 (c ) 1.65, CHCl3).
-13.1 (c 12.88, CHCl3). Anal. Calcd for C34H30O10: C, 68.22;
H, 5.05. Found: C, 67.99; H, 5.21.
D
The literature17b shows the enantiomeric resolution of racemic
2d using a chiral column.
The solution of 3′b (349 mg, 0.583 mmol) in AcOEt (13 mL)
was hydrogenated by Pd-black (70.0 mg) under hydrogen
atmosphere at 3 atm at room temperature. After 2 h, the
mixture was filtered with Celite, and the filtrate was concen-
trated and recrystallized from CHCl3 to give pure 3b (243 mg,
quant) as colorless needles.
(S)-4-Cya n op h en yl m et h yl su lfoxid e (2e): a colorless
crystal; 1H NMR δ 2.78 (s, 3H), 7.78 (d, 2H, J ) 8.5 Hz), 7.85
(d, 2H, J ) 8.5 Hz); 13C NMR δ 43.8, 114.6, 117.6, 124.2, 132.8,
151.3. Daicel Chiralcel OJ column at λ ) 267 nm, n-hexane/
2-propanol (9:1) as eluent and a flow rate of 1.0 mL/min: tR
1
3b: mp 187 °C dec (from CHCl3); H NMR δ 3.36 (br, 2H),
(R) ) 53.5 min, tR (S) ) 59.6 min, ee ) 65%; [R]25 -89.4 (c )
D
3.80 (s, 6H), 5.92 (s, 2H), 6.87-6.90 (m, 4H), 7.42 (t, 2H, J )
7.6 Hz), 7.89 (d, 2H, J ) 7.6 Hz); 13C NMR δ 55.9, 71.3, 112.0,
118.1, 120.1, 132.4, 134.3, 159.8, 164.2, 167.8; IR (KBr) 3235,
1775, 1740, 1715, 1600 cm-1; [R]25D ) -115.3 (c 7.13, acetone).
Anal. Calcd for C20H18O10: C, 57.42; H, 4.34. Found: C, 57.03;
H, 4.45.
1.12, EtOH) (lit.17d ((S)-2e; 92% ee); [R]D -120 (c ) 1.07,
EtOH)).
(S)-4-Br om op h en yl m eth yl su lfoxid e (2f): a colorless
crystal; 1H NMR δ 2.72 (s, 3H), 7.52 (d, 2H, J ) 8.7 Hz), 7.67
(d, 2H, J ) 8.7 Hz); 13C NMR δ 43.9, 125.0, 125.3, 132.4, 144.7.
Daicel Chiralcel OD column at λ ) 252 nm, n-hexane/2-
propanol (99:1) as eluent and a flow rate of 0.8 mL/min: tR
Gen er a l P r oced u r e for Asym m etr ic Oxid a tion of Su l-
fid es. To a stirred suspension of CTAB (0.04 mmol) and 3b
(0.02 mmol) in toluene (5.0 mL) and H2O (0.10 mL) was added
PhIO2 (0.10 mmol), and the mixture was stirred for 1 h. Then,
a solution of sulfide 1 (0.20 mmol) in toluene (1.0 mL) was
added to the stirred suspension and was stirred for 2-48 h.
The reaction mixture was quenched by the addition of aqueous
saturated NaHCO3 and then extracted with AcOEt, dried over
MgSO4, filtered, and evaporated. The residue was purified by
column chromatography (SiO2/CH2Cl2/acetone ) 4:1) to give
pure sulfoxide 2, the enantiomeric excess of which was deter-
mined by HPLC. Absolute configurations were assigned by
comparison of the sign of specific rotation with literature
data.17
(R) ) 85.1 min, tR (S) ) 89.3 min, ee ) 58%; [R]25 -75.7 (c )
D
1.50, CHCl3) (lit.3g ((S)-2f; 79% ee); [R]D -105.2 (c ) 0.44,
CHCl3)).
(S)-p-An isyl m eth yl su lfoxid e (2g): a colorless oil; 1H
NMR δ 2.70 (s, 3H), 3.86 (s, 3H), 7.03 (d, 2H, J ) 8.9 Hz),
7.60 (d, 2H, J ) 8.9 Hz); 13C NMR δ 43.9, 55.5, 114.8, 125.4,
136.5, 161.9. Daicel Chiralcel OD column at λ ) 243 nm,
n-hexane/2-propanol (9:1) as eluent and a flow rate of 1.0 mL/
min: tR (R) ) 15.8 min, tR (S) ) 17.3 min, ee ) 46%; [R]25
D
-81.5 (c ) 1.12, CHCl3) (lit.17c ((R)-2g; 99.5% ee); [R]D +165.9
(c ) 0.38, CHCl3)).
(S)-Meth yl 2-n a p h th yl su lfoxid e (2h ): a colorless crystal;
1H NMR δ 2.73 (s, 3H), 7.51-7.54 (m, 3H), 7.85-7.93 (m, 3H),
8.15 (s, 1H); 13C NMR δ 43.7, 119.3, 123.9, 127.3, 127.7, 128.0,
128.4, 129.5, 132.8, 134.3, 142.6. Daicel Chiralpak AD column
at λ ) 223 nm, n-hexane/2-propanol (95:5) as eluent and a flow
rate of 0.5 mL/min: tR (R) ) 64.5 min, tR (S) ) 69.5 min, ee )
51%; [R]25D -69.9 (c ) 1.38, acetone) (lit.17c ((R)-2h ; 77.5% ee);
[R]D +102.6 (c ) 1.9, acetone)).
To confirm the reproducibility of the asymmetric oxidation
of sulfides, these reactions were run at least twice. The condi-
tions to determine the ee values and [R]D values are as follows:
(S)-Meth yl p-tolyl su lfoxid e (2a ): a colorless crystal; 1H
NMR δ 2.42 (s, 3H), 2.71 (s, 3H), 7.33 (d, 2H, J ) 8.1 Hz),
7.54 (d, 2H, J ) 8.1 Hz); 13C NMR δ 21.4, 44.0, 123.4, 129.9,
141.3, 142.3. Daicel Chiralcel OD column at λ ) 243 nm,
n-hexane/2-propanol (9:1) as eluent and a flow rate of 1.0 mL/
(S)-1-Th ia in d a n e 1-oxid e (2i): a colorless oil; 1H NMR δ
3.23-3.41 (m, 3H), 3.82-3.90 (m, 1H), 7.40-7.54 (m, 3H), 7.84
(d, 1H, J ) 7.5 Hz); 13C NMR δ 31.4, 52.7, 126.0, 126.7, 128.2,
132.3, 143.1, 144.7. Daicel Chiralpak AD column at λ ) 267
nm, n-hexane/2-propanol (9:1) as eluent and a flow rate of 1.0
min: tR (R) ) 10.5 min, tR (S)) 11.3 min, ee ) 53%; [R]25
D
-75.8 (c ) 1.22, CHCl3) (lit.17c ((R)-2a ; 99.5% ee); [R]D +145 (c
) 0.75, CHCl3)).
(S)-Meth yl 4-n itr op h en yl su lfoxid e (2b): a colorless
crystal; 1H NMR δ 2.77 (s, 3H), 7.84 (d, 2H, J ) 8.7 Hz), 8.40
mL/min: tR (S) ) 16.3 min, tR (R) ) 19.3 min, ee ) 38%; [R]25
D
+110.3 (c ) 0.787, acetone) (lit.17a ((R)-2i; 2.6% ee); [R]D -7.3
(c ) 1.10, acetone), lit.17e((R)-2i; 99% ee); [R]D -285 (c ) 1.5,
acetone)).
(16) Ishihara, K.; Gao, Q.; Yamamoto, H. J . Org. Chem. 1993, 58,
6917-6919.
(17) (a) Takata, T.; Yamazaki, M.; Fujimori, K.; Kim, Y.-H.; Oae,
S.; Iyanagi, T. Chem. Lett. 1980, 1441-1444. (b) Gargaro, G.; Gaspar-
rini, F.; Misiti, D.; Palmieri, G.; Pierini, M.; Villani, C. Chromatograph-
ia 1987, 24, 505-509. (c) Brunel, J .-M.; Diter, P.; Duetsch, M.; Kagan,
H. B. J . Org. Chem. 1995, 60, 8086-8088. (d) Holland, H. L.;
Bornmann, M. J .; Lakshmaiah, G. J . Mol. Catal. B: Enzymatic 1 1996,
97-102. (e) Allenmark, S. G.; Anderson, M. A. Tetrahedron: Asym-
metry 1996, 7, 1089-1094.
Ack n ow led gm en t. This research was supported in
part by a Grant-in-Aid for Scientific Research from the
Ministry of Education, Science and Culture, J apan.
J O982295T