Photopromoted Ru-catalyzed asymmetric aerobic sulfide oxidation and epoxidation using water as a proton transfer mediator

Article abstract of DOI:10.1021/ja104184r

Ru(NO)-salen complexes were found to catalyze asymmetric aerobic oxygen atom transfer reactions such as sulfide oxidation and epoxidation in the presence of water under visible light irradiation at room temperature. Oxidation of sulfides including alkyl aryl sulfides and 2-substituted 1,3-dithianes using complex 2 as the catalyst proceeded with moderate to high enantioselectivity of up to 98% ee, and epoxidation of conjugated olefins using complex 3 as the catalyst proceeded with good to high enantioselectivity of 76-92% ee. Unlike biological oxygen atom transfer reactions that need a proton and electron transfer system, this aerobic oxygen atom transfer reaction requires neither such a system nor a sacrificial reductant. Although the mechanism of this oxidation has not been completely clarified, some experimental results support the notion that an aqua ligand coordinated with the ruthenium ion serves as a proton transfer agent for the oxygen activation process, and it is recycled and used as the proton transfer mediator during the process. Thus, we have achieved catalytic asymmetric oxygen atom transfer reaction using molecular oxygen that can be carried out under ambient conditions.

Full text of DOI:10.1021/ja104184r

Published on Web 08/11/2010
Photopromoted Ru-Catalyzed Asymmetric Aerobic Sulfide
Oxidation and Epoxidation Using Water as a Proton Transfer
Mediator
Haruna Tanaka,† Hiroaki Nishikawa,† Tatsuya Uchida,† and Tsutomu Katsuki*,‡
Department of Chemistry, Faculty of Science, Graduate School, and Institute for AdVanced
Study, Kyushu UniVersity, Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan
Received May 15, 2010; E-mail: katsuscc@chem.kyushu-univ.jp
Abstract: Ru(NO)-salen complexes were found to catalyze asymmetric aerobic oxygen atom transfer
reactions such as sulfide oxidation and epoxidation in the presence of water under visible light irradiation
at room temperature. Oxidation of sulfides including alkyl aryl sulfides and 2-substituted 1,3-dithianes using
complex 2 as the catalyst proceeded with moderate to high enantioselectivity of up to 98% ee, and
epoxidation of conjugated olefins using complex 3 as the catalyst proceeded with good to high
enantioselectivity of 76-92% ee. Unlike biological oxygen atom transfer reactions that need a proton and
electron transfer system, this aerobic oxygen atom transfer reaction requires neither such a system nor a
sacrificial reductant. Although the mechanism of this oxidation has not been completely clarified, some
experimental results support the notion that an aqua ligand coordinated with the ruthenium ion serves as
a proton transfer agent for the oxygen activation process, and it is recycled and used as the proton transfer
mediator during the process. Thus, we have achieved catalytic asymmetric oxygen atom transfer reaction
using molecular oxygen that can be carried out under ambient conditions.
1. Introduction
In 1993, Mukaiyama and co-workers developed an asym-
metric oxygen atom transfer process using a Mn-salen/O2/
aldehyde system, in which the aldehyde serves as a sacrificial
reductant, and achieved moderate to good enantioselective
aerobic epoxidation (up to 92% ee) and sulfide oxidation.3 In
1985, Groves and Quinn reported that a dioxo ruthenium(VI)-
porphyrin complex catalyzed epoxidation in the absence of a
sacrificial reductant. This epoxidation catalysis by the ruthenium
complex was explained by a unique mechanism; an oxo
ruthenium(IV) species resulting from epoxidation undergoes
disproportionation to give the starting dioxo ruthenium(VI)
species and a Ru(II) species that can be reoxidized by oxygen
at room temperature to the oxo ruthenium(IV) species.4 Later,
Che et al. reported the asymmetric version of this epoxidation
using 8 atm pressure of oxygen, albeit with moderate enanti-
Oxidation and reduction are two fundamental chemical
reactions, and both reactions have been extensively studied for
many years. Today, asymmetric hydrogenation of olefins and
carbonyl compounds can be carried out with almost complete
enantioselectivity in quantitative yield. Two hydrogen atoms
are incorporated into substrates without any byproducts. Asym-
metric oxygen atom transfer reactions such as epoxidation and
sulfide oxidation can also be carried out with high enantiose-
lectivity, but the atom efficiency of the reactions is still mostly
unsatisfactory because of the use of oxidants of low active
oxygen content, except for a few examples.1 On the other hand,
it is well-known that most biological oxygen atom transfer
reactions are highly, often completely, enantioselective and
ecologically sustainable, because they use molecular oxygen in
the air as an oxidant at body temperature and the only coproduct
is water. However, biological reactions include sophisticated
electron and proton transfer steps to activate molecular oxygen
and are currently difficult to implement with a synthetic
catalyst.2 Thus, development of a simple oxidation catalyst that
promotes asymmetric aerobic oxygen atom transfer reactions
at room temperature without using a complicated electron and
proton transfer system has long been a challenge in oxidation
chemistry.
(2) For reviews of biological epoxidation, see: (a) Guengerich, F. P.
J. Biochem. Mol. Toxicol. 2007, 21, 163–168. (b) Mahammed, A.;
Gross, Z. J. Am. Chem. Soc. 2005, 127, 2883–2887. (c) Groves, J. T.
Proc. Natl. Acad. Sci. U.S.A. 2003, 100, 3569–3574. (d) van Rantwijk,
F.; Sheldon, R. A. Curr. Opin. Biotechnol. 2000, 11, 554–564. (e)
Sono, M.; Roach, M. P.; Coulter, E. D.; Dawson, J. H. Chem. ReV.
1996, 96, 2841–2887.
(3) (a) Mukaiyama, T.; Yamada, T.; Nagata, T.; Imagawa, K. Chem. Lett.
1993, 327–328. (b) Mukaiyama, T.; Yamada, T. Bull. Chem. Soc. Jpn.
1995, 68, 17–35. (c) Nagata, T.; Imagawa, K.; Yamada, T.; Mu-
kaiyama, T. Bull. Chem. Soc. Jpn. 1995, 68, 3241–3246. For other
asymmetric oxidation using Mukaiyama condition, see: (d) Bolm, C.;
Schlingloff, G.; Weickhardt, K. Angew. Chem., Int. Ed. Engl. 1994,
33, 1848–1849.
† Department of Chemistry, Faculty of Science, Graduate School.
‡ Institute for Advanced Study.
(1) (a) Wong, O. A.; Shi, Y. Chem. ReV. 2008, 108, 3958–3987. (b)
Aziridines and Epoxides in Organic Synthesis; Yudin, A. K., Ed.;
Wiley-VCH: Weinheim, 2006. (c) Katsuki, T. In ComprehensiVe
Coordination Chemistry II; McCleverty, J. A., Meyer, T. J., Eds.;
Elsevier Pergamon: Oxford, 2004; Vol. 9, pp 207-264. (d) Johnson,
R. A.; Sharpless, K. B. In Catalytic Asymmetric Synthesis, 2nd ed.;
Ojima, I., Ed.; Wiley-VCH: New York, 2000; pp 231-280.
(4) (a) Groves, J. T.; Quinn, R. J. Am. Chem. Soc. 1985, 107, 5790–
5792. (b) Recently, aerobic oxidation of alkenes to aldehydes via
epoxides under ambient conditions was reported: Jiang, G.; Chen, J.;
Thu, H.-Y.; Huang, J.-S.; Zhu, N.; Che, C.-M. Angew. Chem. Int. Ed
2008, 47, 6638–6642.
9
12034 J. AM. CHEM. SOC. 2010, 132, 12034–12041
10.1021/ja104184r  2010 American Chemical Society

Asymmetric Aerobic Sulfide Oxidation and Epoxidation
A R T I C L E S
Scheme 1. The Proposed Mechanism for Asymmetric Aerobic
Oxidation of Alcohols Catalyzed by Ru-salen Complexesa
Scheme 2. An Expected Mechanism for Asymmetric Aerobic
Oxygen Atom Transfer Catalyzed by Ru-salen Complexes
a The salen ligand is omitted for clarity, except for donor atoms.
oselectivity (up to 73% ee).5 Subsequently, Beller et al. reported
the modified version of Sharpless asymmetric dihydroxylation,
another oxygen atom transfer reaction, using molecular oxygen
at 50 °C as the terminal oxidant.6 Realization of asymmetric
aerobic oxygen atom transfer reactions under ambient conditions
is still a challenging target.
In the aforementioned biological oxidation, the transferred
proton for molecular oxygen activation is discarded as water,
the byproduct of the oxygen activation process. This fact poses
a question whether oxygen atom transfer reaction can be
performed without any proton and electron transfer system, if
the byproduced water is recycled as the proton source. In this
paper, we describe a new method for asymmetric aerobic
oxidation of sulfides and epoxidation under ambient conditions
in which water serves as a proton transfer mediator.
There have been recent studies of aerobic oxidations such as
alcohol oxidation and oxidative coupling of 2-naphthol that
involve asymmetric catalysis of dehydrogenation using molec-
ular oxygen.7 We discovered that Ru(NO)-salen(X) complexes
(X ) Cl or OH) catalyze aerobic oxidative kinetic resolution
of racemic alcohols, coupling of 2-naphthol and desymmetri-
zation of meso-diols under ambient and visible light irradiation
conditions (Scheme 1).8 Irradiation promotes the dissociation
of the nitrosyl group to give a Ru(solvent)-salen(X) species,8e
and the Ru(ROH)-salen(X) species generated in the presence
of alcohol catalyzes aerobic alcohol oxidation under
irradiation.8d Moreover, the kinetic study of these alcohol
oxidations disclosed that the rate laws of these oxidation
reactions depend on the apical ligand of the catalyst; the rate
of the reaction catalyzed by Ru(NO)-salen(Cl) complexes (1
and 2) shows the first order dependence on the concentration
of molecular oxygen, while the reaction catalyzed by Ru(NO)-
salen(OH) complexes shows fractional order dependence on the
oxygen concentration.8d This indicates that an oxygen molecule
participates in the transition state of this oxidation by complex
1 or 2. With these results and hypothesis, we further inferred
that molecular oxygen coordinates with the ruthenium(III) ion
prior to the single electron transfer event and the resulting
superoxide is also bound to the oxidized ruthenium(IV) ion.
When an alcohol substrate exists in the reaction mixture, it is
oxidized.8 Superoxide is nucleophilic and is relatively nonre-
active with nucleophilic substrates. In most biological oxidation
reactions, an umpolung step, conversion of a superoxo to an
electrophilic hydroperoxo or oxo species, is included, but it
requires a sophisticated electron and proton transfer system.2
The oxidation with 1 or 2 also shows the first order dependence
on alcohol concentration,8d and the alcohol should be coordi-
nated with the ruthenium ion and be acidic. On the other hand,
it is known that superoxo species can undergo proton coupled
electron transfer to give hydroperoxo species, if a proton donor
exists nearby it.9,10 Thus, the superoxo species a is likely to
undergo proton coupled electron transfer to generate a more
electrophilic hydroperoxo species b. Based on these consider-
ations, we expected that aerobic oxygen atom transfer would
occur in a pathway via b competitively with the alcohol
oxidation, if the reaction mixture includes an appropriate
nucleophile such as a sulfide or an alkene (Scheme 2). Moreover,
oxygen atom transfer by species b generates an (alkoxo)(hy-
droxo)Ru species c that could tautomerize to an (alcohol)-
(oxo)Ru species d.11 An alcohol is regenerated by this tau-
tomerization process and the alcohol can serve as a proton
transfer mediator. Moreover, if the oxo species d undergoes
another oxo transfer reaction, it produces a Ru(III)-salen species
(5) Lai, T.-S.; Zhang, R.; Cheung, K.-K.; Kwong, H.-L.; Che, C.-M. Chem.
Commun. 1998, 1583–1584.
(9) Shan, X.; Que, L., Jr. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 5340–
5345.
(6) (a) Do¨bler, C.; Mehltretter, G.; Beller, M. Angew. Chem., Int. Ed.
1999, 38, 3026–3028. (b) Do¨bler, C.; Mehltretter, G.; Sundermeier,
U.; Beller, M. J. Organomet. Chem. 2001, 621, 70–76.
(10) For examples of seven-coordinate transition metal complexes, see: (a)
Gross, Z.; Mahammed, A. J. Mol. Catal. A: Chem. 1999, 14, 367–
372. (b) Corazza, F.; Solari, E.; Florlani, C.; Chiesi-Villa, A.; Guastini,
C. J. Chem. Soc., Dalton Trans. 1990, 1335–1344. (c) Repo, T.;
Klinga, M.; Pietika¨inen, P.; Leskela¨, M.; Uusitalo, A.-M.; Pakkanen,
T.; Hakala, K.; Aaltonen, P.; Lo¨fgren, B. Macromolecules 1997, 30,
171–175. (d) Watanabe, A.; Uchida, T.; Irie, R.; Katsuki, T. Proc.
Natl. Acad. Sci. U.S.A. 2004, 101, 5737–5742.
(7) For reviews on asymmetric aerobic oxidation of alcohols and cross-
coupling of 2-naphthols, see: (a) Wills, M. Angew. Chem., Int. Ed.
2008, 47, 4264–4267. (b) Irie, R.; Katsuki, T. Chem. Rec. 2004, 4,
96–109. (c) Stahl, S. S. Angew. Chem., Int. Ed. 2004, 43, 3400–3420.
(d) Schultz, M. J.; Sigman, M. S. Tetrahedron 2006, 62, 8227–8241.
(e) Stolz, B. M. Chem. Lett. 2004, 33, 362–367. (f) Kozlowski, M. C.;
Morgan, B. J.; Linton, E. C. Chem. Soc. ReV. 2009, 38, 3193–3207.
(8) (a) Masutani, K.; Uchida, T.; Irie, R.; Katsuki, T. Tetrahedron Lett.
2000, 41, 5119–5123. (b) Irie, R.; Masutani, K.; Katsuki, T. Synlett
2000, 1433–1436. (c) Shimizu, H.; Nakata, K.; Katsuki, T. Chem. Lett.
2002, 1080–1081. (d) Shimizu, H.; Onitsuka, S.; Egami, H.; Katsuki,
T. J. Am. Chem. Soc. 2005, 127, 5396–5413. (e) Works, C. F.; Jocher,
C. J.; Bart, G. D.; Bu, X.; Ford, P. C. Inorg. Chem. 2002, 41, 3728–
3739.
(11) For the examples of oxo-hydroxo and oxo-aqua tautomerization, see:
(a) Jin, N.; Spiro, T. G.; Groves, J. T. J. Am. Chem. Soc. 2007, 129,
12416–12417. (b) Chen, K.; Costas, M.; Kim, J.; Tipton, A. K.; Que,
L., Jr, J. Am. Chem. Soc. 2002, 124, 3026–3035. (c) Lee, K. A.; Nam,
W. J. Am. Chem. Soc. 1997, 119, 1916–1922. (d) Bernadou, J.;
Meunier, B. Chem. Commun. 1998, 2167–2173. (e) Bernadou, J.;
Fabiano, A.-S.; Robert, A.; Meunier, B. J. Am. Chem. Soc. 1994, 116,
9375–9376.
9
J. AM. CHEM. SOC. VOL. 132, NO. 34, 2010 12035

A R T I C L E S
Tanaka et al.
Scheme 3. A Preliminary Experiment on Asymmetric Aerobic
Oxidation Catalyzed by Ru-salen Complex 1
Scheme 4. A Possible Reaction Pathway in the Presence of an
Aqua Ligand
that can undergo single electron transfer upon irradiation8d under
aerobic conditions, regenerating the starting ruthenium(IV)
species a. Based on this mechanistic consideration, the aerobic
oxygen atom transfer reaction was expected to occur via this
catalytic pathway. However, this catalytic pathway includes two
different oxygen atom transfer steps, and it is preferred that the
two different active species would show the same asymmetric
catalysis. Recently, we discovered that the complexes of salen
ligands bearing a binaphthyl moiety show excellent enantiose-
lectivity in an identical sense, irrespective of their configura-
tion.12 Thus, we expected that the above oxidation could be
realized in a highly enantioselective manner by using a
ruthenium-salen complex.
Table 1. Aerobic Oxidation of 2-Chlorophenyl Methyl Sulfide with
Ru(NO)-salen Complexes as the Catalysta
run
cat.
solvent
time (h)
yieldb (%)
eec (%)
1
2
3
4
1
1
1
1
1
1
2
2
2
2
3
CHCl3
toluene
acetone
AcOEt
AcOEt
AcOEt
AcOEt
AcOEt
AcOEt
AcOEt
AcOEt
24
24
24
24
48
24
48
72
48
48
48
3
4
7
18
59
75 (S)
78 (S)
72 (S)
80 (S)
82 (S)
5d
6e
7d
8d
9
2. Results and Discussion
nr
56f
93 (S)
2.1. Asymmetric Aerobic Oxidation of Sulfides. We first
examined the oxidation of methyl phenyl sulfide and o-
chlorophenyl methyl sulfide in chloroform with 1 in the presence
of 1 equiv of ethanol under ambient air (Scheme 3). The
reactions had good enantioselectivity (76 and 88% ee, respec-
tively); however, the oxidation of sulfides and the alcohol
oxidation almost stopped after a short time and the yields of
the sulfoxides were low, though the yield (9%) of o-chlorophe-
nyl methyl sulfoxide was nearly four times better than that
(2.5%) of methyl phenyl sulfoxide. These results suggested that
catalyst poisoning by the product is responsible for the low yield.
During the study, we found that the reaction proceeded in a
better yield (16%) even in the absence of ethanol, albeit with a
slightly reduced selectivity (80% ee) (Scheme 3). According to
the elementary analysis of complex 1 prepared based on the
literature,13 it contains water molecule. The water should be
lattice water, but it can coordinate at the apical position of the
resulting denitrosylated Ru complex upon irradiation and serve
as the hydrogen bond donor. Similar alcohol coordination has
been observed in aerobic alcohol oxidation (Scheme 1).8d These
results were reminiscent of the following advantages of water
as a proton transfer mediator: (i) water is less oxidizable than
alcohol, (ii) water could be a better H-bond donor than
alcohols,14 and (iii) it has two protons. Thus, water has the
specific advantage of proton coupled electron transfer from the
aqua ligand generating (hydroperoxo)(hydroxo) species (b, R
) H). The hydroxo group can then form a hydrogen bond with
the distal oxygen atom of the hydroperoxo group to the metal
ion (Scheme 4). This type of hydrogen bond cannot be formed
when the hydrogen bond donor is an alcohol. Sharpless and
co-workers have proposed that, in a metal catalyzed epoxidation
using alkyl hydroperoxide as the terminal oxidant, the hydrogen
bond formation between a hydroxo group and the distal oxygen
atom of an alkylperoxo group facilitates O-O bond cleavage
and epoxidation.15 Moreover, in biological system catalyzed
99f
92 (S)
99d,f(89)f,g
34d,f
18f
94 (94)g (S)
94 (S)
10h
11
15 (R)
a Reactions were run at 25 °C on a 0.1 mmol scale with Ru-salen
complex (5 mol %) as a catalyst in the presence of H2O (1 equiv) in 1.0
mL of solvent under air and visible light irradiation with a halogen
lamp, unless otherwise noted. b Determined by HPLC analysis using
phenanthrene as an internal standard. c Determined by HPLC analysis
using a chiral stationary phase. d The reaction was run in 0.5 mL of
AcOEt. e The reaction was carried out in the dark. f Isolated yield. g The
reaction was run in 2.5 mL of AcOEt on a 0.5 mmol scale. h The
reaction was performed without addition of water.
cytochrome P-450, a superoxo species is converted to a
hydroperoxo species via a proton and electron transfer, and the
resulting hydroperoxo species is converted into an oxo species
via protonation at the oxygen atom distal to the ferric ion.2b
The nature of species e should be similar to that of the
protonated or hydrogen-bonded hydroperoxo species, which
might undergo O-O bond fission16 or the desired oxygen atom
transfer directly (Scheme 4). We were intrigued by the
hypothesis that water supplies two protons which are retrieved
during the catalytic cycle.
Based on this hypothesis, we next examined the oxidation
of o-chlorophenyl methyl sulfide with 1 in the presence of 1
equiv of water under ambient air (Table 1). The reactions in
chloroform, toluene and acetone were slow, and the yields of
the sulfoxide were less than 7% (runs 1-3). A better yield was
obtained in ethyl acetate (AcOEt) without eroding the enanti-
oselectivity (run 4), and the yield was further improved to 59%
as the substrate concentration was increased and the reaction
time was elongated (run 5). No reaction occurred without
irradiation (run 6). We expected that the yield might be
improved if catalyst poisoning by the sulfoxide could be
(15) Michaelson, R. C.; Palermo, R. E.; Sharpless, K. B. J. Am. Chem.
Soc. 1977, 99, 1990–1992.
(12) Matsumoto, K.; Saito, B.; Katsuki, T. Chem. Commun. 2007, 3619–
3627.
(16) (a) Company, A.; Go´mez, L.; Gu¨ell, M.; Ribas, X.; Luis, J. M.; Que,
L., Jr.; Costas, M. J. Am. Chem. Soc. 2007, 129, 15766–15767. (b)
Chen, K.; Que, L., Jr. J. Am. Chem. Soc. 2001, 123, 6327–6337.
(13) Uchida, T.; Irie, R.; Katsuki, T. Tetrahedron 2000, 56, 3501–3509.
(14) Mayer, U. Pure Appl. Chem. 1979, 51, 1697–1712.
9
12036 J. AM. CHEM. SOC. VOL. 132, NO. 34, 2010

Asymmetric Aerobic Sulfide Oxidation and Epoxidation
A R T I C L E S
Table 2. Aerobic Oxidation of Sulfides with Ru(NO)-salen
Complex 2 as the Catalysta
Table 3. Aerobic Epoxidation of trans-ꢀ-Methylstyrene with
Ru(NO)-salen Complexes as Catalysta
d
run
sulfide
yieldb (%)
eec (%)
config
1
2
3
4
PhSMe
p-ClPhSMe
p-MePhSMe
o-MePhSMe
mesityl methyl sulfide
BnSMe
2-phenyl-1,3-dithiane
2-(t-butyl)-1,3-dithiane
74
69
61
86
18
26
57
98
94
84
91
96
72
75
98
91
S
S
S
S
S
S
d
run
cat.
solvent
yieldb (%)
eec (%)
config
5
1e,f
2e,f
3e
4e,f
5e
6
1
2
3
3
3
3
3
3
3
3
CHCl3
CHCl3
CHCl3
(CHCl2)2
ClC6H5
CH3C6H5
AcOEt
ClC6H5
ClC6H5
ClC6H5
14g
traceg
28
27
>99
90
89
86
83
1R,2R
1R,2R
1S,2S
1S,2S
1S,2S
1S,2S
1S,2S
1S,2S
6e
7e
8
1S,2S
1S,2S
46g
58
a Reactions were carried out at 25 °C in the presence of water (1
26g
28g
59 (58)h
nr
equiv) in 2.5 mL of ethyl acetate for 48 h on a 0.5 mmol scale under
7
77
oxygen and visible light irradiation with
a halogen lamp, unless
87 (88)h
otherwise noted. b Isolated yield. c Determined by HPLC analysis with a
chiral stationary phase, as described in the Experimental Section.
d Absolute configuration was determined by chiroptical comparison.
e Sulfide was added dropwise.
8
9i
10j
nr
a Reactions were carried out at 25 °C in 2.5 mL of solvent for 36 h
on a 0.5 mmol scale without adding water under oxygen and visible
light irradiation with a halogen lamp, unless otherwise noted. b Isolated
yield. c Determined by HPLC or GLC analysis using a chiral stationary
phase as described in the Experimental Section. d Determined by
chiroptical comparison. e 1.0 equiv of water was added. f Reaction was
suppressed by using a complex possessing a sterically congested
coordination sphere, which allows the coordination of molecular
oxygen in preference to a more bulky sulfoxide. Thus, we
examined oxidation using complex 2 that carries two methyl
groups near the ruthenium ion8d as the catalyst. To our delight,
a remarkably improved enantioselectivity of 93% ee was
obtained, though the yield was still moderate (run 7). Eventually,
a satisfactory yield was obtained by extending the reaction time
(run 8) or by performing the reaction under oxygen atmosphere
(run 9). The reaction was also performed without adding water
under oxygen atmosphere (run 10). The reaction proceeded with
the same enantioselectivity, albeit slowly. The reaction with
complex 3, a diastereomer of 1, was of low enantioselectivity
(run 11). Overoxidation is often observed in oxidation of
sulfides.17 It is, however, noteworthy that no overoxidation to
sulfone was observed in the present oxidation.
Under oxygen atmosphere, oxidation of other aryl methyl
sulfides using 2 as the catalyst also proceeded with high
enantioselectivity (up to 96%) (Table 2, runs 1-4). However,
bulky sulfides such as mesityl methyl sulfide were more slowly
oxidized, and the enantioselectivity was moderate (run 5). The
reaction of benzyl methyl sulfide was slow, and the enantiose-
lectivity was moderate (75% ee) (run 6). The reactions of
2-substituted 1,3-dithianes proceeded with high diastereo- and
enantioselectivity (runs 7 and 8). No overoxidation to sulfone
or disulfoxide was also observed in this oxidation.17
2.2. Asymmetric Aerobic Epoxidation of Conjugated Ole-
fins. The successful results of asymmetric aerobic oxidation of
sulfides prompted us to further explore the epoxidation of
olefins, which are weaker nucleophiles than sulfides. The
epoxidation of trans-ꢀ-methylstyrene 4 using Ru(NO)-salen
complexes (1-3) as catalysts was examined in chloroform at
room temperature in the presence of water (1 equiv) under
oxygen atmosphere. The reactions were carried out under
irradiated conditions (Table 3). The epoxidation using complex
1 as the catalyst occurred slowly with modest enantioselectivity
(run 1). Complex 2 showed excellent enantioselectivity, but its
catalytic activity for epoxidation was poor (run 2). However,
complex 3, a poor catalyst for oxidation of sulfides, was found
to show high enantioselectivity, albeit with modest yield (run
3). Thus, the reaction was further optimized with respect to
run on
a
0.1 mmol scale. g Determined by GLC analysis using
bicyclohexyl as an internal standard. h For 48 h. i Carried out in the
dark. j Carried out in nitrogen atmosphere.
solvent by using 3 as the catalyst, and better yield (58%) was
obtained in chlorobenzene, albeit with slightly reduced enan-
tioselectivity (run 5). The reactions in toluene and ethyl acetate
were slower and less selective (runs 6 and 7). Although the
best enantioselectivity was obtained in the reaction in chloro-
form, chlorobenzene was chosen in consideration of yield for
the solvent of the following reactions. The catalytic activities
of complex 313 pretreated with 1 equiv of water and complex
3 were almost identical, supporting the observation that water
molecule is recycled during the oxidation process (Vide infra)
(runs 5 and 8). Epoxidation did not occur without irradiation
or in nitrogen atmosphere under otherwise identical conditions,
suggesting that irradiation and the presence of oxygen are
essential for this oxidation (runs 9 and 10).
Under the optimized conditions, we examined the epoxidation
of several other olefins (Table 4). Epoxidation of 2-[(E)-1-
propenyl]naphthalene 5 and m-methyl[(E)-1-propenyl]benzene
6 also proceeded with high enantioselectivity (runs 1 and 2).
Epoxidation of p-methyl[(E)-1-propenyl]benzene 7 proceeded
with good enantioselectivity (run 3); however, as the reaction
time extended the enantiomeric excess of the epoxide decreased
to some extent. This is because the epoxide slowly rearranged
to a ketone, and the rearrangement of the major enantiomer of
the epoxide to the ketone is faster than that of the minor
enantiomer (runs 4 and 5).18 The epoxidations of (E)-R,ꢀ-
dimethylstyrene 8 and cis-ꢀ-methylstyrene 9 were highly
enantioselective, albeit with modest yields (runs 6 and 7). It is
of note that the epoxidation is stereospecific; trans- and cis-ꢀ-
methystyrenes gave the corresponding trans- and cis-epoxides,
respectively.18,19
2.3. Validation of the Working Hypothesis on the Role of
Water as a Proton Transfer Mediator in Aerobic Oxygen
Atom Transfer Reaction. Based on the working hypothesis that
water could serve as a proton transfer mediator, we examined
(17) For reviews on asymmetric sulfoxidation, see: (a) Legros, J.; Dehli,
J. R.; Bolm, C. AdV. Synth. Catal. 2005, 347, 19–31. (b) Kagan, H. B.;
Luukas, T. O. Catalytic Asymmetric sulfide Oxidations. In Transition
Metals for Organic Synthesis, 2nd ed.; Beller, M., Bolm, C., Eds.;
Wiley-VCH: Weinheim, Germany, 2004; Vol. 2, pp 479-495.
(18) For the enantiomer-differentiating epoxide-rearrangement using com-
plex 3 as the catalyst, see: (a) Takeda, T.; Irie, R.; Shinoda, Y.; Katsiki,
T. Synlett 1999, 1157–1159. (b) Nakata, K.; Takeda, T.; Mihara, J.;
Hamada, T.; Irie, R.; Katsuki, T. Chem.sEur. J. 2001, 7, 3776–3782.
9
J. AM. CHEM. SOC. VOL. 132, NO. 34, 2010 12037

A R T I C L E S
Tanaka et al.
Table 4. Asymmetric Aerobic Epoxidation with Ru(NO)-salen
Complex 3 as the Catalysta
Table 5. Epoxidation of trans-ꢀ-Methylstyrene in 18O2 Atmospherea
run
time (h)
yieldb (%)
18O contentc (%)
% eed
1
2
3
4
6
12
24
36
39
46
49
53
76
79
81
82
85
84
85
85
d
run
substrate
yieldb (%)
eec (%)
config
a Reactions were carried out using 3 as the catalyst at 25 °C in 0.5
mL of chlorobenzene on a 0.1 mmol scale without adding water under
oxygen (18O2) and visible light irradiation with a halogen lamp, unless
otherwise noted. b Determined by 1H NMR analysis using phenanthrene
as an internal standard. c Determined by ESI-TOF-MS analysis (average
of three runs). d Determined by HPLC analysis using a chiral stationary
phase as described in the Experimental Section.
1
2
5
6
7
7
7
8
9
75
67
92
90
77
78
76
88
90
3e
4h,i
5h
6
52 (1)f,g
44f
58 (3)f,g
55
2R,3R
1S,2R
7e
34 (3)f,g
Scheme 6. The Yield of Epoxide (Black Line) and the 18O Content
of the Epoxide Product (Red Line) vs Reaction Time Plots for the
Epoxidation of ꢀ-Methylstyrene with Complex 3 as a Catalyst in
the Presence of H218O (1 equiv)
a Reactions were carried out using 3 as the catalyst at 25 °C in 2.5
mL of chlorobenzene for 48 h on a 0.5 mmol scale without adding
water under oxygen and visible light irradiation with a halogen lamp,
unless otherwise noted. b Isolated yield. c Determined by HPLC or GLC
analysis using a chiral stationary phase as described in the Experimental
Section. d Determined by chiroptical comparison. e For 36 h.
f Determined by 1H NMR analysis using phenanthrene as an internal
standard. g The number in parentheses is the yield of ketone. h Reaction
was run on a 0.1 mmol scale. i For 12 h.
Scheme 5. Epoxidation under Anhydrous or Hydrous Conditions
This result, in addition to the previous result that no
epoxidation occurs in the absence of molecular oxygen (Table
3, run 10), proves that molecular oxygen is the terminal oxidant.
2.3.3. 18O Incorporation Experiment: Asymmetric Epoxida-
tion of trans-ꢀ-Methylstyrene Using 3 as the Catalyst in the
Presence of 18O-Labeled Water. The expected reaction pathway
(Scheme 2) includes a dihydroxo species (c, R ) H) that is in
equilibrium with an aqua(oxo) species (d, R ) H), and a water
oxygen atom can be incorporated into epoxides via the dihy-
droxo and aqua(oxo) tautomerization.11 To investigate the
plausibility of the oxygen atom incorporation from water, we
examined the epoxidation of trans-ꢀ-methylstyrene in the
presence of 1 equiv of H218O under 16O2 atmosphere. As
expected, 18O incorporation was observed, but the 18O incor-
poration value of the epoxide product exceeded 50% (Scheme
6). We also examined the oxidation of o-chlorophenyl methyl
sulfide in the presence of H218O under 16O2 atmosphere. The
18O incorporation value of the sulfoxide product was 70% at
11% conversion, and it diminished to 43% at 94% conversion
(Scheme 7). These results support the assumed mechanism for
incorporation of the water oxygen atom and regeneration of
water. However, in the assumed reaction pathway for aerobic
oxidation (Scheme 2), the oxygen atom incorporation from water
occurs only in the second step, and the 18O incorporation value
must be e50%. Thus, these results suggested that 16O/18O
exchange between H218O and an active species can occur also
in the first step. Although more detailed experiments are
required, the reaction pathway via dioxo species f (Scheme 4)
may explain the experimental results.
Ru-catalyzed asymmetric aerobic oxidation in the absence of
sacrificial reductant and achieved highly enantioselective oxida-
tion of sulfides and epoxidation. To explore the feasibility of
the hypothesis, we performed several experiments.
2.3.1. Study of the Effect of Water on Epoxidation Rate:
Asymmetric Epoxidation of trans-ꢀ-Methylstyrene Using 3 as
the Catalyst under Anhydrous and Hydrous Conditions. In the
hypothesis, a metal-bound water molecule plays a crucial role
in the activation of a putative superoxo or hydroperoxo species.
Complex 3 prepared according to the literature13 contains a
water molecule. Thus, complex 3 was dehydrated in vacuo at
ca. 380 °C and used as catalyst for the epoxidation of trans-
ꢀ-methylstyrene under two different conditions, anhydrous and
hydrous, to study the effect of water on epoxidation (Scheme
5). Epoxidation using dried 3 was sluggish, and the enantiose-
lectivity was lower and its reproducibility was poor. The
epoxidation catalysis of 3 was restored by adding water (wet
3) (cf. Table 3, run 5), supporting the hypothesis on the role of
water.
2.3.2. 18O Incorporation Experiment: Epoxidation of trans-ꢀ-
Methylstyrene with 3 as the Catalyst in 18O2. To verify that
molecular oxygen is the terminal oxidant of this oxidation, the
18O incorporation experiment was performed. The epoxidation
of trans-ꢀ-methylstyrene in 18O2 atmosphere revealed that 18O
incorporation increased from 76 to 82% as the reaction
proceeded (Table 5). This result suggests that most of the
incorporated oxygen atom originates from molecular oxygen
but some originates from another oxygen source.
9
12038 J. AM. CHEM. SOC. VOL. 132, NO. 34, 2010

Asymmetric Aerobic Sulfide Oxidation and Epoxidation
A R T I C L E S
Scheme 7. Conversion of Sulfide (Black Line) and the 18O Content
of the Sulfoxide Product (Red Line) vs Reaction Time Plots for
Asymmetric Oxidation of o-Chlorophenyl Methyl Sulfide in the
Presence of H218O
bromide via Suzuki-Miyaura coupling.20 18O2 and H218O (18O
content g 98%) were purchased from Taiyo Nippon Sanso
Corporation.
4.2. Experimental Procedures for Asymmetric Oxidation
of Sulfides and Epoxidation.
4.2.1. Typical Procedure for Asymmetric Aerobic Oxidation
of Sulfides Using 2 as the Catalyst under Oxygen Atmosphere.
Complex 2 (25.5 mg, 25 µmol) and water (9.0 µL, 0.5 mmol)
were placed in a Schlenk tube, which was previously purged
with oxygen, and AcOEt (2.5 mL) was added to the mixture.
The resultant solution was stirred under irradiation with a halogen
lamp at room temperature. After 30 min, sulfide (0.5 mmol) was
added to the solution and stirred for 48 h under oxygen and
irradiation at room temperature in the closed tube. The mixture
was concentrated and the residue was chromatographed on an
NH-silica gel column to give the corresponding sulfoxide. All
the fractions containing the sulfoxide were collected.21 The
enantiomeric excess of the sulfoxide was determined by HPLC
analysis using a chiral stationary phase.
All the above observations are consistent with the reaction
pathway of asymmetric aerobic oxygen atom transfer using
water as the proton transfer mediator described in Schemes 2
and 4.
3. Conclusion
4.2.1.1. (S)-o-Chlorophenyl Methyl Sulfoxide (Table 1,
Run 9). Colorless oil. Yield 99% (94% ee). [R]2D5 -257.5 (c 3.3,
acetone). Lit.22 [96% ee, (S)-isomer; [R]2D5 -266.5 (c 2.0, acetone)].
1H NMR (CDCl3, 400 MHz): δ 7.97 (dd, J ) 1.7, 7.8 Hz, 1H),
7.55 (ddd, J ) 1.5, 7.3, 7.8 Hz, 1H), 7.45 (ddd, J ) 1.7, 7.3, 7.8
Hz, 1H), 7.40 (dd, J ) 1.5, 7.8 Hz, 1H), 2.83 (s, 3H). 13C NMR
(CDCl3, 100 MHz): δ 143.1, 131.6, 129.4, 129.4, 127.8, 124.9,
41.5 ppm. HPLC: tR (S) )15.2 min, tR (R) )22.4 min (DAICEL
CHIRALCEL OB-H; flow rate, 0.5 mL/min; hexane/EtOH/i-PrOH
) 90/5/5).
In summary, we have demonstrated that Ru(NO)(salen)
complexes 2 and 3 can catalyze aerobic oxygen atom transfer
reactions such as oxidation of sulfides and epoxidation of
conjugated olefins in the presence of water with good to high
enantioselectivity at room temperature under irradiated condi-
tions. The terminal oxidant is molecular oxygen. Water serves
as a proton transfer mediator for these oxygen atom transfer
reactions. That is, water is recycled during the oxidation process
that includes two oxidation steps. These aerobic oxygen atom
transfer reactions do not need a special proton and electron
transfer system. The present results pave the way for ecologi-
cally sustainable oxygen atom transfer. The mechanism of these
reactions is now under investigation.
4.2.1.2. (S)-Methyl Phenyl Sulfoxide (Table 2, Run 1). Color-
less oil. Yield 74% (94% ee). [R]2D5 -136.3 (c 0.33, acetone). Lit.22
1
[96% ee, (S)-isomer; [R]2D5 -141.0 (c 0.43, acetone)]. H NMR
(CDCl3, 400 MHz): δ 7.67-7.65 (m, 2H), 7.56-7.48 (m, 3H), 2.73
(s, 3H). 13C NMR (CDCl3, 100 MHz): δ 145.4, 130.7, 129.0, 123.2,
44.0 ppm. HPLC: tR (S) ) 22.5 min, tR (R) ) 36.2 min (DAICEL
CHIRALCEL OB-H; flow rate, 0.5 mL/min; hexane/EtOH/i-PrOH
) 90/5/5).
4. Experimental Section
4.2.1.3. (S)-p-Chlorophenyl Methyl Sulfoxide (Table 2,
Run 2). Colorless oil. Yield 69% (84% ee). [R]2D5 -98.0 (c 2.0,
acetone). Lit.22 [94% ee (S)-isomer; [R]2D5 -114.9 (c 1.28, acetone)].
1H NMR (CDCl3, 400 MHz): δ 7.61-7.59 (d, J ) 8.4 Hz, 2H),
7.52-7.51 (d, J ) 8.4 Hz, 2H), 2.73 (s, 3H). 13C NMR (CDCl3,
100 MHz): δ 144.0, 136.9, 129.3, 124.6, 44.1 ppm. HPLC: tR (S)
) 16.2 min, tR (R) ) 24.0 min (DAICEL CHIRALCEL OB-H;
flow rate, 0.5 mL/min; hexane/i-PrOH ) 80/20).
4.2.1.4. (S)-Methyl p-Methylphenyl Sulfoxide (Table 2,
Run 3). Colorless oil. Yield 61% (91% ee). [R]2D5 -134.6 (c 0.22,
acetone). Lit.22 [96% ee (S)-isomer; [R]2D5 -140.3 (c 0.63, acetone)].
1H NMR (CDCl3, 400 MHz): δ 7.55-7.53 (d, J ) 8.0 Hz, 2H),
7.35-7.33 (d, J ) 8.0 Hz, 2H), 2.73 (s, 3H), 2.42 (s, 3H). 13C
NMR (CDCl3, 100 MHz): δ 142.1, 141.2, 129.7, 123.2, 43.9, 21.4
ppm. HPLC: tR (S) ) 9.4 min, tR (R) ) 15.3 min (DAICEL
CHIRALCEL OB-H; flow rate, 0.5 mL/min; hexane/i-PrOH ) 50/
50).
4.1. General. 1H and 13C NMR spectra were recorded at 400
and 100 MHz on a JEOL JNM-AL-400 instrument. All signals
were expressed as ppm downfield from tetramethylsilane used
as an internal standard (δ-value in CDCl3). High-resolution
electron spray ionization mass spectra (HRMS-ESI) were
measured with a BRUKER DALTONICS MICRO TOF-KS1
focus. Optical rotations were measured with a JASCO P-1020
polarimeter. Enantiomeric excesses were determined by HPLC
analysis using SHIMADZU LC-10AT-VP or GLC analysis using
SHIMADZU GC-1700, equipped with a chiral stationary phase.
All the reactions were carried out in a 5 mL Schlenk tube (L:
ca. 13 mm) placed in a cooling bath (25 °C), except the
experiments for Table 1 which were carried out in an air-
conditioned room (25 °C). The reaction mixtures were irradiated
by the light (intensity: ca. 90 mW/cm2) from a halogen lamp
(6423 FO, fiber optic lamp, PHILIPS) at a distance of 0.5 cm
through a vinyl covered optical fiber in water to keep the reaction
temperature constant at 25 °C. Column chromatography was
conducted on a silica gel 60N (spherical, neutral), 63-210 µm,
available from Kanto Chemical Co., Inc., or a Chromatorex NH
(spherical, basic), 100-200 µm, available from Fuji Silysia
Chemical Ltd. Preparative thin layer chromatography was
performed on 0.5 mm × 20 cm × 20 cm E. Merck silica gel
(19) Stereospecific asymmetric epoxidation reactions using a Ru complex
have been reported: (a) End, N.; Pfaltz, A. Chem. Commun. 1998,
589–590. (b) Gross, Z.; Ini, S. Org. Lett. 1999, 2077–2080. (c) Tes,
M. K.; Do¨bler, C.; Bhor, S.; Klawonn, M.; Ma¨gerlein, W.; Hugl, H.;
Beller, M. Angew. Chem., Int. Ed. 2004, 43, 5255–5260. (d) Tes,
M. K.; Bhor, S.; Klawonn, M.; Anilkumar, G.; Jiao, H.; Spannenberg,
A.; Do¨bler, C.; Ma¨gerlein, W.; Hugl, H.; Beller, M. Chem.sEur. J.
2006, 12, 1875–1888.
plate (60 F-254). Ru(NO)-salen complexes 1,13
2
8d and 313 were
(20) (a) Miyaura, N.; Yamada, K.; Suzuki, A. Tetrahedron Lett. 1979, 36,
3437–3440. (b) Uenishi, J.; Beau, J.-M.; Armstrong, R. W.; Kishi, Y.
J. Am. Chem. Soc. 1987, 109, 4756–4758.
prepared according to the literature. Commercial trans-ꢀ-
methylstyrene and cis-ꢀ-methylstyrene were distilled before use.
2-[(E)-1-Propenyl]naphthalene and (E)-R,ꢀ-dimethylstyrene were
prepared from the corresponding alkenylboronic acid and aryl
(21) Diter, P.; Taudien, S.; Samuel, O.; Kagan, H. B. J. Org. Chem. 1994,
59, 370–373.
(22) Egami, H.; Katsuki, T. J. Am. Chem. Soc. 2007, 129, 8940–8941.
9
J. AM. CHEM. SOC. VOL. 132, NO. 34, 2010 12039

A R T I C L E S
Tanaka et al.
4.2.1.5. (S)-Methyl o-Methylphenyl Sulfoxide (Table 2,
Run 4). Colorless oil. Yield 86% (96% ee). [R]2D5 -211.8 (c 2.7,
acetone). Lit.23 [53% ee, (S)-isomer; [R]D20 -122 (c 2.0, acetone)].
1H NMR (CDCl3, 400 MHz): δ 7.96 (dd, J ) 1.5, 7.8 Hz, 1H),
7.45 (ddd, J ) 0.7, 7.6, 7.8 Hz, 1H), 7.39 (ddd, J ) 1.5, 7.3, 7.6
Hz, 1H) 7.21 (dd, J ) 0.7, 7.3 Hz, 1H), 2.69 (s, 3H), 2.38 (s, 3H).
13C NMR (CDCl3, 100 MHz): δ 143.8, 133.8, 130.5, 127.3, 122.9,
42.1, 18.2 ppm. HPLC: tR (R) ) 103.7 min, tR (S) ) 109.8 min
(DAICEL CHIRALPAC IC; flow rate, 0.5 mL/min; hexane/i-PrOH
) 90/10).
NMR (CDCl3, 400 MHz): δ 7.35-7.24 (m, 5H), 3.57 (d, J ) 2.2
Hz, 1H), 3.04 (dq, J ) 2.2, 5.1 Hz, 1H), 1.45 (d, J ) 5.1 Hz, 3H).
13C NMR (100 MHz): δ 137.6, 128.3, 127.9, 125.4, 59.5, 59.0,
17.9 ppm. GLC: tR (1S,2S) ) 23.8 min, tR (1R,2R) ) 25.9 min
[InertCap CHIRAMIX: 70 °C (5.5 min) to 110 °C (46 °C/min)
then 110 to 133 °C (1 °C/min)].
4.2.2.2. trans-1-(2-Naphthyl)-1,2-epoxypropane (Table 4,
Run 1). White solid. Yield 75% (92% ee). [R]2D5 -42.4 (c
1
0.90,CHCl3) H NMR (CDCl3, 400 MHz): δ 7.83-7.76 (m, 4H),
7.51-7.30 (m, 3H), 3.74 (d, J ) 2.0 Hz, 1H), 3.14 (dq, J ) 2.0,
5.3 Hz,1H), 1.50 (d, J ) 5.3 Hz, 3H). 13C NMR (CDCl3, 100 MHz):
δ 135.2, 133.2, 133.2, 128.2, 127.7, 126.3, 125.9, 125.0, 123.0,
59.8, 59.1, 12.9 ppm. HPLC: tR (minor) ) 16.5 min, tR (major) )
18.2 min (DAICEL CHIRALCEL OB-H; flow rate, 1.0 mL/min;
hexane/i-PrOH ) 99.9/0.1; at 30 °C).
4.2.1.6. (S)-Mesityl Methyl Sulfoxide (Table 2, Run 5). Yellow
oil. 18% (72% ee). [R]D25 -179.2 (c 1.0, CHCl3). Lit.24 [98% ee,
(S)-isomer; [R]D -241 (c 1.0, CHCl3)]. 1H NMR (CDCl3, 400
MHz): δ 6.85 (s, 3H), 2.84 (s, 3H), 2.50 (s, 6H), 2.24 (s, 3H). 13
C
NMR (CDCl3, 100 MHz): δ 141.3, 137.3, 130.7, 38.5, 20.8, 18.0
ppm. HPLC: tR (S) ) 10.0 min, tR (R) ) 11.1 min (DAICEL
CHIRALCEL OJ-H; flow rate, 1.0 mL/min; hexane/i-PrOH ) 95/
5).
4.2.2.3. trans-1-(m-Methylphenyl)-1,2-epoxypropane (Table
4, Run 2). Colorless oil. Yield 67% (90% ee). [R]2D5 -44.6 (c 0.35,
CHCl3). 1H NMR (CDCl3, 400 MHz): δ 7.26-7.06 (m, 4H), 3.54
(d, J ) 2.2 Hz, 1H), 3.1-3.0 (dq, J ) 5.1, 2.2 Hz, 1H), 2.34 (s,
3H), 1.45 (d, J ) 5.1 Hz, 3H). 13C NMR (100 MHz): δ 138.0,
137.5, 128.6, 128.2, 125.9, 122.6, 59.6, 58.9, 21.5, 18.0 ppm. HPLC:
tR (minor) ) 8.8 min, tR (major) ) 13.3 min (DAICEL CHIRAL-
PAC AS-H; flow rate, 0.5 mL/min; hexane/i-PrOH ) 95/5).
4.2.2.4. trans-1-(p-Methylphenyl)-1,2-epoxypropane (Table
4, Run 5). Colorless oil. Yield 58% (76% ee). [R]2D4 -30.3 (c 0.59,
CHCl3). 1H NMR (CDCl3, 400 MHz): δ 7.26-7.06 (m, 4H), 3.54
(d, J ) 2.0 Hz, 1H), 3.03 (dq, J ) 5.1, 2.0 Hz, 1H), 2.34 (s, 3H),
1.44 (d, J ) 5.1 Hz, 3H). 13C NMR (100 MHz): δ 137.6, 134.5,
129.0, 125.4, 59.6, 58.9, 21.3, 18.0 ppm. HPLC: tR (minor) ) 8.6
min, tR (major) ) 10.3 min (DAICEL CHIRALPAC AS-H; flow
rate, 0.5 mL/min; hexane/i-PrOH ) 90/10).
4.2.1.7. (S)-Benzyl Methyl Sulfoxide (Table 2, Run 6). Color-
less solid. Yield 26% (75% ee). [R]2D4 +79.9 (c 0.56, EtOH). Lit.22
[87% ee, (S)-isomer; [R]2D4 +97.9 (c 0.25, EtOH)]. 1H NMR (CDCl3,
400 MHz): δ 7.41-7.28 (m, 5H), 4.07 (d, J ) 12.9 Hz, 1H), 3.93
(d, J ) 12.9 Hz, 1H), 2.46 (s, 3H). 13C NMR (CDCl3, 100 MHz):
δ 129.9, 129.6, 128.9, 128.4, 60.4, 37.3 ppm. HPLC: tR (S) ) 20.1
min, tR (R) ) 25.1 min (DAICEL CHIRALCEL OB-H; flow rate,
0.5 mL/min; hexane/i-PrOH ) 80/20).
4.2.1.8. (1S,2S)-2-Phenyl-1,3-dithiane 1-Oxide (Table 2,
Run 7). Colorless solid. Yield 57% (98% ee). [R]2D4 +122.4 (c 0.86,
CHCl3). Lit.25 [99% ee, (1S,2S)-isomer; [R]2D4 +106.48 (c 0.88,
CHCl3)]. 1H NMR (400 MHz): δ 7.43-7.36 (m, 5H), 4.59 (s, 1H),
3.60-3.55 (m, 1H), 2.90 (ddd, J ) 2.7, 12.4, 12.4 Hz, 1H), 2.79
(ddd, J ) 2.9, 13.2, 13.2 Hz, 1H), 2.69 (dddd, J ) 1.2, 2.4, 13.2,
13.2 Hz, 1H), 2.58-2.51 (m, 1H), 2.44-2.32 (m, 1H). 13C NMR
(100 MHz): δ 133.0, 129.1, 128.8, 128.4, 69.6, 54.7, 31.4, 29.5
ppm. HPLC: tR (1R,2R) ) 15.2 min, tR (1S,2S) ) 25.0 min
(DAICEL CHIRALCEL AD-H; flow rate, 0.5 mL/min; hexane/i-
PrOH ) 75/25).
4.2.1.9. (1S,2S)-2-tert-Butyl-1,3-dithiane 1-Oxide (Table 2,
Run 8). Colorless solid. Yield 98% (91% ee). [R]2D5 -51.5 (c 0.87,
EtOH). Lit.26 [35% ee, (1S,2S)-isomer]; [R]D -13 (EtOH). 1H NMR
(CDCl3, 400 MHz): δ 3.52 (s, 1H), 3.39 (ddd, J ) 3.7, 3.7, 12.7
Hz, 1H), 2.70 (ddd, J ) 2.9, 12.7, 13.0 Hz, 1H), 2.63 (pseudodd,
J ) 2.9, 8.54 Hz, 2H), 2.45-2.38 (m, 1H), 2.32-2.18 (m, 1H),
1.25 (s, 9H). 13C NMR (CDCl3, 100 MHz): δ 77.2, 55.7, 36.3, 30.7,
30.3, 28.8 ppm. HPLC: tR (1R,2R) ) 18.1 min, tR (1S,2S) ) 24.6
min (DAICEL CHIRALCEL OD-H; flow rate, 0.5 mL/min; hexane/
i-PrOH ) 90/10).
4.2.2. Typical procedure for Asymmetric Aerobic Epoxida-
tion Using 3 as the Catalyst under Oxygen Atmosphere. Complex
3 (24.8 mg, 25 µmol) and chlorobenzene (2.5 mL) were placed in
a Schlenk tube, which was previously purged with oxygen. Alkene
(0.5 mmol) was added to the solution and stirred for 36 h under
oxygen and irradiation in the closed tube. The mixture was
chromatographed on an NH-silica gel column with pentane and
Et2O (1:0 to 20:1) to give the corresponding epoxide. The
enantiomeric excess of the epoxide was determined by GLC or
HPLC analysis using a chiral stationary phase.
4.2.2.5. (2R,3R)-2-Phenyl-2,3-epoxybutane (Table 4, Run
6). Colorless oil. Yield 55% (88% ee). [R]2D5 +14.8 (c 0.88, CHCl3).
Lit.28 [99% ee, (2S,3S)-isomer; [R]D -16.0 (c 1.0, CHCl3)]. H
NMR (CDCl3, 400 MHz): δ 7.36-7.24 (m, 5H), 2.95 (q, J ) 5.4
Hz, 1H), 1.66 (s, 3 H), 1.43 (d, J ) 5.4 Hz, 3H). 13C NMR (100
MHz): δ 143.0, 128.3, 127.1, 125.0, 62.3, 60.3, 17.4, 14.4 ppm.
HPLC: tR (1R,2R) ) 16.5 min, tR (1S,2S) ) 20.0 min (DAICEL
CHIRALPAC AS-H; flow rate, 0.5 mL/min; hexane).
20
1
4.2.2.6. (1S,2R)-cis-ꢀ-Methylstyrene Oxide (Table 4, Run
7). Colorless oil. Yield 34% (90% ee). [R]2D5 +43.8 (c 0.15, CHCl3).
Lit.29 [>99% ee, (1S,2R)-isomer; [R]D20 +47.5 (c 1.17, CHCl3)]. 1H
NMR (CDCl3, 400 MHz): δ 7.37-7.25 (m, 5H), 4.06 (d, J ) 4.4
Hz, 1H), 3.34 (dq, J ) 4.4, 5.4 Hz, 1H), 1.08 (d, J ) 5.4 Hz, 3H).
13C NMR (100 MHz): δ 135.3, 127.8, 127.3, 126.4, 57.5, 55.2,
12.7 ppm. GLC: tR (1S,2R) ) 24.1 min, tR (1R,2S) ) 25.6 min
[InertCap CHIRAMIX: 70 °C (5.5 min) to 110 °C (46 °C/min)
then 110 to 133 °C (1 °C/min)].
4.3. Confirmation of the Effect of Water on Asymmetric
Aerobic Oxidation: Asymmetric Epoxidation of trans-ꢀ-Methyl-
styrene Using Dried or Wet 3 as the Catalyst. Epoxidation with
dried 3 as the catalyst: Complex 3 (4.9 mg, 5.0 µmol) was placed
in a Schlenk tube. The Schlenk tube was heated at 380 °C with
a heat gun for 5 min in vacuo followed by cooling at room
temperature and purging with O2 gas. After that, chlorobenzene
(0.5 mL), trans-ꢀ-methylstyrene (13 µL, 0.1 mmol), and a small
1
amount of phenanthrene as an internal standard for H NMR
4.2.2.1. trans-1-Phenyl-1,2-epoxypropane (Table 3, Run 8).
Colorless oil. Yield 58% (88% ee). [R]2D4 -41.7 (c 0.88, CHCl3).
Lit.27 [95.7% ee, (1S,2S)-isomer; [R]D25 -46.9 (c 0.88, CHCl3)]. 1H
analysis were added to the Schlenk tube. An aliquot (40 µL) of
this solution was taken out of the Schlenk tube as the zero point.
1
The aliquot was diluted by CDCl3 and submitted to H NMR
analysis. The reaction mixture was stirred at room temperature
for 36 h under visible light irradiation in the closed tube. A
small quantity of the samples were taken out for 1H NMR
analysis and GLC analysis with InertCap CHIRAMIX [70 °C
(23) Imamoto, T.; Koto, H. Chem. Lett. 1986, 6, 967–968.
(24) Garc´ıa Ruano, J. L.; Alemparte, C.; Aranda, M. T.; Zarzuelo, M. M.
Org. Lett. 2003, 5, 75–78.
(25) Tanaka, T.; Saito, B.; Katsuki, T. Tetrahedron Lett. 2002, 43, 3259–
3262.
(26) Auret, B. J.; Boyd, D. R.; Cassidy, E. S.; Turley, F.; Drake, A. F.;
Mason, S. F. J. Chem. Soc., Chem. Commun. 1983, 282–283.
(27) Wang, Z.-X.; Tu, Y.; Frohn, M.; Zhang, J.-R.; Shi, Y. J. Am. Chem.
Soc. 1997, 119, 11224–11235.
(28) Capriati, V.; Florio, A.; Luisi, R.; Nuzzo, I. J. Org. Chem. 2004, 69,
3330–3335.
(29) Witkop, B.; Foltz, C. M. J. Am. Chem. Soc. 1957, 79, 197–201.
9
12040 J. AM. CHEM. SOC. VOL. 132, NO. 34, 2010

Asymmetric Aerobic Sulfide Oxidation and Epoxidation
A R T I C L E S
(5.5 min) to 110 °C (46 °C/min) then 110 to 133 °C (1 °C/
min)], respectively. The results are shown in Scheme 5.
Epoxidation with wet 3 as the catalyst: The epoxidation was
carried out in the same manner as that with dried 3, except that
water (1.8 µL, 0.1 mmol) was added to the tube together with trans-
ꢀ-methylstyrene.
110 to 133 °C (1 °C/min)], and ESI-TOF-MS analysis. The results
are shown in Table 5.
4.6. Confirmation of the Incorporation of the Oxygen
Atom from Water to the Product.
4.6.1. Asymmetric Epoxidation of trans-ꢀ-Methylstyrene
Using 3 as the Catalyst in the Presence of 18O-Labeled
Water. A solution of complex 3 in chlorobenzene (0.05 M, 0.1
mL, 5 µmol) and H218O (2.0 µL, 0.1 mmol) was added to 0.3 mL
of chlorobenzene under O2 atmosphere in a 5 mL Schlenk tube
and stirred for 1 h at room temperature under visible light
irradiation. A solution of trans-ꢀ-methylstyrene in chlorobenzene
(1 M, 0.1 mL, 0.1 mmol) with a small amount of phenanthrene as
an internal standard was added to the mixture. The reaction was
carried out under irradiation in the closed tube. Samples (10 µL)
ESI-TOF-MS analysis of 3 and dried 3 gave the ion peak [M+]
at m/z 956.2428 and 956.2436, respectively (m/z calcd for [M+]
C60H44N3O3Ru, 956.2437).
4.4. Proof of the Necessity of Irradiation for Aerobic
Oxidation: The Reaction of trans-ꢀ-Methylstyrene Using 3 as
the Catalyst in the Dark. Complex 3 (4.9 mg, 5 µmol) and
chlorobenzene (0.5 mL) were placed in a Schlenk tube, which was
previously purged with oxygen. To the solution were added trans-
ꢀ-methylstyrene (13.0 µL, 0.1 mmol) and a small amount of
1
were taken out at an appropriate interval for H NMR, GLC with
1
phenanthrene as an internal standard for H NMR analysis. An
InertCap CHIRAMIX [70 °C (5.5 min) to 110 °C (46 °C/min),
then 110 to 133 °C (1 °C/min)], and ES-TOF-MS analyses. The
results are described in Scheme 6.
aliquot (20 µL) of this solution was taken out of the Schlenk tube
as the zero point. The aliquot was diluted by CDCl3 and submitted
to 1H NMR analysis. The Schlenk tube was light-shielded, and the
mixture was stirred for 36 h under irradiation in the closed tube.
4.6.2. Asymmetric Oxidation of o-Chlorophenyl Methyl
Sulfide Using 1 in the Presence of 18O-Labeled Water. Complex
1 (5.0 mg, 5.0 µmol) and dry AcOEt (0.5 mL) were placed in a 5
mL Schlenk tube under oxygen atmosphere. H218O (1.8 µL, 0.1
mmol, content of 18O > 98%) and a small amount of phenanthrene
as an internal standard for HPLC analysis were added to the
suspension. The mixture was stirred for 30 min under irradiation
with a halogen lamp. Then, o-chlorophenyl methyl sulfide (13 µL,
0.1 mmol) was added to the mixture. An aliquot (10 µL) of this
suspension was taken out of the Schlenk tube as the zero point.
The aliquot was diluted by EtOH and submitted to HPLC analysis.
The reaction was carried out for 48 h under irradiation and oxygen
atmosphere, and traced by HPLC analysis. Yield and enantiomeric
excess of o-chlorophenyl methyl sulfoxide were determined by
HPLC analysis using chiral stationary phase [DAICEL CHIRAL-
CEL OB-H (hexane/i-PrOH/EtOH ) 90/5/5)], and the 18O content
of each sulfoxide was determined by ESI-TOF-MS analysis. The
results are shown in Scheme 7.
1
No formation of the epoxide was detected by H NMR analysis.
4.5. Confirmation of the Stoichiometric Oxidant of the
Present Asymmetric Oxidation.
4.5.1. The Reaction of trans-ꢀ-Methylstyrene Using 3 as
the Catalyst under Nitrogen Atmosphere. Under nitrogen atmo-
sphere, Ru-salen complex 3 (4.9 mg, 5 µmol) and chlorobenzene
(0.5 mL) were placed in a Schlenk tube. To the solution were added
trans-ꢀ-methylstyrene (13.0 µL, 0.1 mmol) and a small amount of
1
phenanthrene as an internal standard for H NMR analysis. An
aliquot (20 µL) of this solution was taken out of the Schlenk tube
as the zero point. The aliquot was diluted by CDCl3 and submitted
to 1H NMR analysis. The reaction mixture was stirred under visible
light irradiation for 36 h in the closed tube. No formation of the
1
epoxide was detected by H NMR analysis.
4.5.2. 18O Incorporation Experiment: Asymmetric Epoxida-
tion of trans-ꢀ-Methylstyrene Using 3 as the Catalyst in 18O2.
Complex 3 (4.9 mg, 5 µmol) and chlorobenzene (0.5 mL) were
placed in a Schlenk tube, which was previously purged with 18O2.
To the solution were added trans-ꢀ-methylstyrene (13.0 µL, 0.1
mmol) and a small amount of phenanthrene as an internal standard
for 1H NMR analysis. An aliquot (40 µL) of this solution was taken
out of the Schlenk tube as the zero point. The aliquot was diluted
by CDCl3 and submitted to 1H NMR analysis. The reaction mixture
was stirred at room temperature under visible light irradiation in
the closed tube. A small quantity of the sample was taken out at
Acknowledgment. Financial support from Specially Promoted
Research 18002011 and the Global COE Program, “Science for
Future Molecular Systems” from the Ministry of Education, Science,
and Culture, Japan, is gratefully acknowledged.
Supporting Information Available: GLC and HPLC condi-
tions and ESI-TOF-MS spectra. This material is available free
of charge via the Internet at http://pubs.acs.org.
1
an appropriate interval for H NMR analysis, GLC analysis with
InertCap CHIRAMIX [70 °C (5.5 min) to 110 °C (46 °C/min) then
JA104184R
9
J. AM. CHEM. SOC. VOL. 132, NO. 34, 2010 12041