Selective oxidation of allylic sulfides by hydrogen peroxide with the trirutile-type solid oxide catalyst LiNbMoO6

Article abstract of DOI:10.1021/jo016013s

Chemoselective sulfur oxidation of allylic sulfides containing double bonds of high electron density due to multiple alkyl substituents or extended conjugation was developed using the composite metal oxide catalyst, LiNbMoO₆, without any epoxidation of the electron-rich double bond(s). Selective oxidation to either the corresponding sulfoxides or the sulfones was realized by controlling the stoichiometry of the quantitative oxidant, H₂0₂. This new oxidant system had general applicability for chemoselective oxidation of various allylic, benzylic, or propargylic sulfides containing unsaturated carbon-carbon bonds with different electron properties. Various functional groups including hydroxy, formyl, and ethers of THP or TBDMS are compatible under this mild oxidation reaction condition.

Full text of DOI:10.1021/jo016013s

8192
J . Org. Chem. 2001, 66, 8192-8198
Selective Oxid a tion of Allylic Su lfid es by Hyd r ogen P er oxid e w ith
th e Tr ir u tile-typ e Solid Oxid e Ca ta lyst LiNbMoO6
Soojin Choi,†,§ J ae-Deuk Yang,‡ Minkoo J i,‡ Hojin Choi,‡ Minyong Kee,‡ Kwang-Hyun Ahn,†
Song-Ho Byeon,† Woonphil Baik,‡ and Sangho Koo*,‡
Department of Chemistry, Kyung Hee University, Yongin, Kyunggi-Do, 449-701, Korea, and
Department of Chemistry, Myong J i University, Yongin, Kyunggi-Do, 449-728, Korea
sangkoo@mju.ac.kr
Received August 8, 2001
Chemoselective sulfur oxidation of allylic sulfides containing double bonds of high electron density
due to multiple alkyl substituents or extended conjugation was developed using the composite metal
oxide catalyst, LiNbMoO6, without any epoxidation of the electron-rich double bond(s). Selective
oxidation to either the corresponding sulfoxides or the sulfones was realized by controlling the
stoichiometry of the quantitative oxidant, H2O2. This new oxidant system had general applicability
for chemoselective oxidation of various allylic, benzylic, or propargylic sulfides containing unsatur-
ated carbon-carbon bonds with different electron properties. Various functional groups including
hydroxy, formyl, and ethers of THP or TBDMS are compatible under this mild oxidation reaction
condition.
In tr od u ction
reaction conditions. The use of reactive electrophilic
oxidants, however, might interfere with chemoselectivity,
especially with sulfides containing nucleophilic functional
groups.5
Organosulfur compounds are useful intermediates for
constructing highly functionalized biologically and me-
dicinally important natural products.1 Among the various
transformations of organic sulfides, chemoselective oxi-
dation to sulfoxides or to sulfones has been widely studied
with regard to extending the carbon skeleton2 and/or
double bond formation3 using the resulting sulfoxides or
sulfones. There is much room for improvement, however,
in the chemoselectivity of this oxidation reaction.
Electrophilic oxidants are useful for the selective
oxidation of sulfide to sulfoxide because the initial
oxidation of a highly nucleophilic sulfide to a sulfoxide
is an easier process than the second oxidation of the
resulting much less nucleophilic sulfoxide to sulfone.4
Thus, selective oxidation of sulfides to sulfoxides or to
sulfones can be realized based on the stoichiometry of
the electrophilic oxidant used under carefully controlled
We studied the oxidation reactions of allylic sulfides
comprising double bonds of high electron density due to
multiple alkyl substituents or extended conjugation. We
were unable to selectively convert these allylic sulfides
to the corresponding sulfoxides or to the sulfones using
well-known conventional oxidants such as m-chloroper-
benzoic acid (MCPBA),6 NaIO4,7 SeO2,8 Oxone,5 the
AcOH-H2O2 system,9 etc., because the electron-rich
double bonds interfered with the selective oxidation of
sulfur in the allylic sulfides. It is critical to use a much
less electrophilic but still reactive oxidant system to
selectively convert these allylic sulfides to the corre-
sponding sulfoxides or to the sulfones. We then reviewed
various metal oxide catalyst-H2O2 oxidant systems,10
which are efficient oxidants rendering both selectivity
(due to low electrophilicity) and reactivity to organosul-
fides. Though somewhat satisfactory results were ob-
tained for allylic sulfides with electron-rich double bonds
due to alkyl substituents, chemoselective oxidation of an
allylic sulfide comprising conjugated polyenes was still
problematic.
* To whom correspondence should be addressed: Professor Sangho
Koo, Department of Chemistry, Myong J i University, San 38-2, Nam-
Dong, Yongin, Kyunggi-Do, 449-728, South Korea. Phone: +82-31-
330-6185. Fax no. 82-31-335-7248.
† Kyung Hee University.
‡ Myong J i University.
§ Current address: R&D Center, Daewoong Pharm. Co., Ltd.,
Seongnam, Kyunggi-do, 462-120, Korea.
(1) General Reviews: (a) Metzner, P.; Thuillier, A. Sulfur Reagents
in Organic Synthesis; Academic Press: London, 1994. (b) Cremlyn, R.
J . an Introduction to Oranosulfur Chemistry; Wiley: Chichester, 1996.
(c) Patai, S.; Rappoport, Z., Ed. Syntheses of Sulphones, Sulphoxides
and Cyclic Sulphides; Wiley: Chichester, 1994. (d) Block, E., Ed.
Advances in Sulfur Chemistry; J AI Press Ltd.; Greenwich, 1994. (e)
Page, P. C. B., Ed. Organosulfur Chemistry I; Springer: Berlin, 1999.
(f) Page, P. C. B., Ed. Organosulfur Chemistry II; Springer: Berlin,
1999.
(2) Marshall, J . A.; Cleary, D. G. J . Org. Chem. 1986, 51, 858-863.
(b) Marshall, J . A.; J enson, T. M.; DeHoff, B. S. J . Org. Chem. 1987,
52, 3860-3866.
(3) Trost, B. M.; Lynch, J .; Renaut, P.; Steinman, D. H. J . Am. Chem.
Soc. 1986, 108, 284-291. (b) Kocienski, P.; Todd, M. J . Chem. Soc.,
Perkin Trans. 1 1983, 1777-1781. (c) J ulia, M.; Lauron, H.; Stacino,
J .-P.; Verpeaux, J .-N. Tetrahedron 1986, 42, 2475-2484. (d) Trost, B.
M.; Salzmann, T. N.; Hiroi, K. J . Am. Chem. Soc. 1976, 98, 4887-
4902.
(4) Bonchio, M.; Conte, V.; De Conciliis, M. A.; Furina, F. D.;
Ballistreri, F. P.; Tomaselli, G. A.; Toscano, R. M. J . Org. Chem. 1995,
60, 4475-4480. (b) Adam, W.; Haas, W.; Lohray, B. B. J . Am. Chem.
Soc. 1991, 113, 6202-6208. (c) Ogura, K.; Suzuki, M.; Tsuchihashi,
G.-I. Bull. Chem. Soc. J pn. 1980, 53, 1414-1416.
(5) Trost, B. M.; Curran, D. P. Tetrahedron Lett. 1981, 22, 1287-
1290.
(6) Nicolaou, K. C.; Magolda, R. L.; Sipio, W. J .; Barnette, W. E.;
Lysenko, Z.; J oullie, M. M. J . Am. Chem. Soc. 1980, 102, 3784-3793.
(7) Leonard, N. J .; J ohnson, C. R. J . Org. Chem. 1962, 27, 282-
284. (b) J ohnson, C. R.; Keiser, J . E. Org. Synth. 1966, 46, 78-80.
(8) Drabowicz, J .; Mikolajczyk, M. Synthesis, 1978, 758-759. (b)
Drabowicz, J .; Lyzwa, P.; Mikolajczyk, M. Phosphorus Sulfur 1983,
17, 169-172.
(9) Oae, S.; Kawai, T.; Furukawa, N. Tetrahedron Lett. 1984, 25,
69-72. (b) Paquette, L. A.; Carr, R. V. C. Org. Synth. 1985, 64, 157.
(10) Schultz, H. S.; Freyermuth, H. B.; Buc, S. R. J . Org. Chem.
1963, 28, 1140.
10.1021/jo016013s CCC: $20.00 © 2001 American Chemical Society
Published on Web 11/02/2001

Selective Oxidation of Allylic Sulfides
J . Org. Chem., Vol. 66, No. 24, 2001 8193
Ta ble 1. Oxid a tion of Allylic Su lfid e 1 by Con ven tion a l
Oxid a n ts
Ta ble 2. Oxid a tion of Allylic Su lfid e 1 by Meta l Oxid e
Ca ta lyst-H2O2 Oxid a n t
yields (%)
oxidant
(equiv)
reaction condition,
solvent temperature (time)
yields (%)
equiv of reaction condition,
entry
2
3
4
entry catalyst
H2O2
temperature (time)
2
3
4
1
2
3
4
5
6
7
8
H2O2 (3)
H2O2 (3)
Oxone (1)
Oxone (3)
NaIO4 (1)
NaIO4 (3)
AcOH
AcOH
rt (24 h)
70 °C (3 h)
MeOH 0 °C (1 h)
MeOH rt (6 h)
90
5
54 15
40 32
-
-
12
-
1
2
3
4
5
6
7
8
MoO3
MoO3
MeReO3
MeReO3
V2O5
V2O5
Na2WO4
Na2WO4
1
3
1
3
1
3
1
3
rt (24 h)
rt (24 h)
0 °C (1 h)
rt (2 h)
0 °C (1 h)
rt (3 h)
64 20
62 26
70 14
-
-
-
5
-
-
28 41
MeOH 0 °C (4 h) to rt (4 h) 66
MeOH rt (6 h) 82
-
2
2
-
74 13
82
-
-
-
-
-
-
MCPBA (1) CH2Cl2 0 °C (4 h) to rt (4 h) 75
MCPBA (3) CH2Cl2 rt (4 h)
-
0 °C (4 h) to rt (1 h) 64 23
rt (1 h) 85
-
22 62
-
The trirutile-type solid oxide, LiNbMoO6, is a stable
metal oxide that has been known for several decades.
Previous reports have described the crystallographic
structure11 and preparation method12 of LiNbMoO6.
Although to our knowledge this composite metal oxide
has never been used as a catalyst of sulfur oxidation, we
examined whether it might confer both selectivity and
reactivity to the oxidant system allowing chemoselective
oxidation of allylic sulfides with electron-rich double
bond(s). Indeed, LiNbMoO6 effectively catalyzed the
chemoselective oxidation of allylic sulfides with electron-
rich double bond(s) due to extended conjugation as well
as alkyl substitutions by hydrogen peroxide. Herein, we
report a study of chemoselective oxidation of allylic
sulfides with electron-rich double bond(s).
sulfoxide 2, sulfone 3, and epoxysulfone 4, is straight-
forward by comparing infrared spectra13 and by 1H NMR
analyses of each compound.
Potassium hydrogen persulfate (KHSO5), commercially
available as Oxone, selectively oxidizes sulfides to sul-
foxides or to sulfones.5 Even under the carefully con-
trolled reaction conditions of slowly adding 1 equiv of
Oxone at 0 °C, however, an appreciable amount of sulfone
3 (15%) was also obtained. Furthermore, excess Oxone
(3 equiv) did not produce complete oxidation of sulfide 1
to sulfone 3 (entries 3 and 4, Table 1). Sodium periodate
(NaIO4) was very effective in the selective oxidation of
sulfide 1 to sulfoxide 2,7 even with excessive use of the
oxidant (entries 5 and 6, Table 1). As was expected based
on the electrophilic nature of the oxidant, 3 equiv of
MCPBA produced epoxysulfone 4 as a major oxidation
product (62%), though selective formation of sulfoxide 2
was observed with 1 equiv of the oxidant at 0 °C (entries
7 and 8, Table 1). Overall, selective oxidation of the allylic
sulfide 1 to sulfoxide 2 was feasible using the above
conventional oxidants under carefully controlled reaction
conditions. Selective oxidation of allylic sulfide 1 to
sulfone 3, however, was not possible due to either too low
or too high reactivity of the above oxidants.
Resu lts a n d Discu ssion
Oxid a tion of Allylic Su lfid e w ith Electr on -Rich
Dou ble Bon d Du e To Alk yl Su bstitu en ts. As a model
compound of an allylic sulfide possessing an electron-rich
double bond due to alkyl substituents, we chose phenyl
prenyl sulfide (1) and attempted oxidation reactions using
the various oxidants mentioned above. Hydrogen perox-
ide is a nucleophilic oxidant which is believed to become
electrophilic in acetic acid solvent, presumably by forming
peracetic acid in situ. With an excess of this oxidant
system (3 equiv of H2O2), only the corresponding sulfoxide
2 was produced in 90% yield at ambient temperature
even after a prolonged reaction time of 24 h without
producing any sulfone 3. Under more vigorous conditions
(heating the reaction mixture to 70 °C for 3 h), sulfoxide
2, sulfone 3, and epoxysulfone 4 were obtained in 5%,
5%, and 12% yield, respectively (entries 1 and 2, Table
1). The formation of epoxysulfone 4 is noteworthy in that
the electron-rich double bonds also attack the electro-
philic oxidant under more vigorous conditions to give
epoxidation as well as sulfur oxidation. The overall yield
was low in this case, presumably due to the instability
of the allylic sulfur compounds under acidic conditions
with heating. The identification of the oxidation products,
To achieve selective oxidation of allylic sulfide 1 to the
corresponding sulfone 3, it was necessary to use a less
electrophilic but still reactive oxidant to avoid epoxidation
of the electron-rich double bond. Thus, an oxidant system
consisting of a metal oxide catalyst and H2O2 as a
quantitative oxidizing agent was used. Selective oxidation
of phenyl prenyl sulfide (1) was attempted using either
1 or 3 equiv of H2O2 with MoO3, MeReO3, V2O5, and Na2-
WO4 as representative metal oxide catalysts.10 MoO3 was
not an efficient oxidation catalyst, providing sulfoxide 2
as the major product with low chemoselectivity regardless
of the amount of H2O2 used (entries 1 and 2, Table 2).
The formation of epoxysulfone 4 (41%) with 3 equiv of
14
H2O2 indicates that MeReO3-H2O2 forms a highly
electrophilic oxidant system, as is the case with MCPBA.
Thus, selective oxidation to sulfoxide 2 was attempted
at 0 °C with 1 equiv of H2O2, but the formation of sulfone
(11) Nam, H.-J .; Kim, H.; Chang, S. H.; Kang, S.-G.; Byeon, S.-H.
Solid State Ionics 1999, 120, 189-195.
(12) Bhuvanesh, N. S. P.; Gopalakrishnan, J . Inorg. Chem. 1995,
34, 4, 3760-3764. (b) Kar, T.; Choudhary, R. N. P. Mater. Lett. 1997,
32, 109-113.
(13) Silverstein, R. M.; Bassler, G. C.; Morrill, T. C. Spectroscopic
Identification of Organic Compounds, 5th ed.; Wiley: New York, 1991;
p 129.

8194 J . Org. Chem., Vol. 66, No. 24, 2001
Choi et al.
Ta ble 3. Oxid a tion of Allylic Su lfid e 5 by Va r iou s
Oxid a n ts
3 (14%) could not be prevented (entries 3 and 4, Table
2). On the other hand, highly chemoselective oxidation
of sulfide 1 to sulfone 3 was realized in good yields with
V2O5 and Na2WO4 catalysts with 3 equiv of H2O2. The
selective oxidation to sulfoxide 2 with 1 equiv of H2O2 at
0 °C was, however, problematic due to the formation
of an appreciable amount of sulfone 3 (entries 5-8,
Table 2).
Thus, certain metal oxides are appropriately selective
and reactive to induce chemoselective oxidation of allylic
sulfide with electron-rich double bonds due to alkyl
substituents to the corresponding allylic sulfone without
epoxidation. The possibility of chemoselective oxidation
of allylic sulfides composed of conjugated polyenes was
then studied with these metal oxides.
yieldsc (%)
oxidantb
reaction condition,
temperature (time)
entry
catalysta
Nb2O5
Nb2O5
MoO3
(equiv)
6
7
1
2
3
4
5
6
7
8
9
H2O2 (1)
H2O2 (2)
H2O2 (1)
H2O2 (2)
H2O2 (1)
H2O2 (2)
H2O2 (1)
H2O2 (2)
H2O2 (1)
H2O2 (2)
rt (4 h)
0 °C (2 h) to rt (22 h)
rt (18 h)
0 °C (2 h) to rt (22 h)
rt (0.5 h)
30
17
25
9
14
23
6
15
10
15
27
50
4
Oxid a tion of Allylic Su lfid e w ith Electr on -Rich
Dou ble Bon d s Du e To Con ju ga tion . We also exam-
ined the oxidation reaction of allylic sulfides composed
of conjugated polyene chains to the corresponding sul-
foxides or sulfones, which can be used in retinoid and
carotenoid syntheses.15 It is critical to use an appropriate
oxidant to selectively oxidize the sulfur moiety without
inducing epoxidation of the conjugated polyenes. The
oxidant for this purpose should be less electrophilic but
still require high reactivity to convert sulfide to sulfone.
We utilized phenyl 3,7,11-trimethyl-2,4,6,10-dodeca-
tetraenyl sulfide (5) as the allylic sulfide containing
conjugated polyene and evaluated whether various oxi-
dants, including a metal oxide catalyst-H2O2, could
selectively oxidize the sulfide 5 to either sulfoxide 6 or
sulfone 7 by controlling the stoichiometry of the oxidants.
The reaction condition was carefully controlled, especially
for the oxidation to sulfone 7 where 2 equiv of oxidant
were used, by maintaining the reaction temperature at
0 °C during and after the addition of the oxidant.
MoO3
MeReO3
MeReO3
Na2WO4
Na2WO4
V2O5
26
0 °C (0.5 h) to rt (0.5 h) 14
rt (0.5 h)
0 °C (1 h) to rt (1 h)
rt (1 h)
0 °C (2 h) to rt (2 h)
40 °C (22 h)
40 °C (22 h)
43
30
56
11
4
10 V2O5
9
7
11 n-Pr4NRuO4 NMO (1)
12 n-Pr4NRuO4 NMO (2)
10
26
10
79
12
0
12
2
13 SeO2
14 SeO2
15
16
H2O2 (1)
H2O2 (1)
MCPBA (1) rt (1 h)
rt (18 h)
0 °C (2 h) to rt (22 h)
-
-
MCPBA (2) 0 °C (0.5 h) to rt (0.5 h) 21
35
a
b
Five mol % of catalyst was used based on sulfide 5. MeOH
was used as solvent for H2O2 oxidant, CH3CN for NMO, and
CH2Cl2 for MCPBA oxidation. c An appreciable amount of side
products were obtained that were presumed to be epoxysulfones,
but the structures were not identified.
The product yields were generally low in the above
process, presumably due to the generation of side-
products such as epoxysulfones. Thus, a more efficient
metal oxide catalyst was developed to achieve selective
oxidation of allylic sulfides composed of conjugated poly-
enes, and not only the allylic sulfides having double bonds
of increased electron density due to alkyl substituents,
to the corresponding sulfoxides or sulfones.
Differently from allylic sulfide 1, which has only one
electron-rich double bond, selective oxidation of allylic
sulfide 5 containing the conjugated triene moiety to the
corresponding sulfoxide 6 or to the sulfone 7 were poor.
In contrast to the composite metal oxide, LiNbMoO6,
which successfully catalyzed the selective oxidation of
allylic sulfide 5 to sulfoxide 6 or sulfone 7 by H2O2 (vide
infra), niobium(V) oxide or molybdenum(VI) oxide alone
were not good catalysts for selective oxidation (entries
1-4, Table 3). Other metal oxide catalysts, such as
MeReO3, Na2WO4, and V2O5 with H2O2 as a quantitative
oxidant did not produce either sulfoxide 6 or sulfone 7
in a chemoselective manner (entries 5-10, Table 3). The
oxidation of sulfide 5 by N-methylmorpholine N-oxide
(NMO) with tetrapropylammonium perruthenate (TPAP)
catalyst16 was very sluggish, and poor yields as well as
no chemoselectivity have been observed with this oxidant
system (entries 11 and 12, Table 3). The oxidation
reaction was then attempted with a nonmetal oxide
catalyst, the SeO2-H2O2 oxidant system, and MCPBA.
With these oxidants, selective formation of sulfoxide 6
was possible, though the product yield was low for SeO2-
H2O2. Chemoselective oxidation to sulfone 7 was, how-
ever, still problematic with those oxidants (entries 13-
16, Table 3).
Ch em oselective Oxid a tion of Va r iou s Allylic Su l-
fid es by th e LiNbMoO6-H2O2 Oxid a n t System . Fine-
tuning the reactivity of oxidants is essential for the
selective oxidation of the sulfur moiety of allylic sulfides
containing conjugated polyenes without inducing oxida-
tion of the double bonds. We hypothesized that a com-
posite metal oxide might have quite different reactivity
than that of each metal oxide in the catalysis of those
selective oxidation reactions with H2O2 as a quantitative
oxidant. The air-stable and easy to handle trirutile-type
solid oxide, LiNbMoO6, was prepared as previously
described,12 and selective oxidation reactions were at-
tempted for allylic sulfides 1 and 5. By controlling the
stoichiometry of the quantitative oxidant, H2O2, remark-
able selectivity as well as reactivity in the oxidation of a
sulfur moiety without any epoxidation was observed.
Sulfoxide 2 was obtained in good yield (77%) when 1
equiv of H2O2 was utilized at 0 °C, although it was
contaminated by the further oxidation product, sulfone
3, in 14% yield. Complete chemoselectivity, however, was
observed in the oxidation to sulfones 3 by using 3 equiv
of H2O2 at ambient temperature, and no epoxidation
product was obtained (entry 1, Table 4). The chemose-
lectivity of the LiNbMoO6 catalyst was even better for
(14) Yamazaki, S. Bull. Chem. Soc. J pn. 1996, 69, 2955-2959.
(15) Choi, H.; J i, M.; Park, M.; Yun, I.-K.; Oh, S.-S.; Baik, W.; Koo
S. J . Org. Chem. 1999, 64, 8051-8053.
(16) Guertin, K. R.; Kende, A. S. Tetrahedron Lett. 1993, 34, 5369-
5372.

Selective Oxidation of Allylic Sulfides
J . Org. Chem., Vol. 66, No. 24, 2001 8195
Ta ble 4. Oxid a tion of Va r iou s Su lfid es by LiNbMoO6
The role of the LiNbMoO6 catalyst in these highly
chemoselective oxidation reactions is not clear at this
point; however, it presumably forms a somewhat reactive
metal-hydroperoxide intermediate with H2O2, which can
selectively oxidize only the sulfur moiety. For the oxida-
tion to occur chemoselectively, the allylic sulfides must
be highly soluble in methanol. In the case of sulfides with
low solubility, some benzene is added to the sulfide
solution to obtain complete dissolution. To improve the
selectivity of the oxidation to sulfoxide, the reaction
temperature is preferably maintained at 0 °C. The
oxidation is generally completed within approximately
1 h at 0 °C in the case of sulfoxides, or approximately 4
h at room temperature in the case of oxidation to sulfones
using 0.05 equiv of the catalyst, LiNbMoO6.
Ca ta lyst-H2O2 Oxid a n t
Con clu sion
Oxidation of allylic sulfides comprising double bond(s)
with high electron density due to many alkyl substituents
or conjugation often accompanies epoxidation of the
electron-rich double bond(s) as well as sulfur-oxidation,
especially with electrophilic oxidants. We have developed
a highly chemoselective oxidant system for sulfur-oxida-
tion consisting of the new composite metal oxide catalyst,
LiNbMoO6, and H2O2 as a quantitative oxidant. With this
less electrophilic but still reactive oxidant system, a
highly chemoselective oxidation of allylic sulfides con-
taining electron-rich double bonds to the corresponding
sulfoxides or sulfones in high yields has been achieved
by controlling the stoichiometry of the quantitative
oxidant, H2O2, without inducing epoxidation.
a
The yields of sulfoxide and sulfone when 1 equiv of H2O2 was
b
used at 0 °C. The yield of sulfone when 3 equiv (2.5 equiv for
entry 2) of H2O2 was used at room temperature.
Exp er im en ta l Section
Gen er a l Exp er im en ta l. 1H (300 MHz) and 13C NMR (75.5
MHz) spectra were recorded in deuterated chloroform (CDCl3).
Solvents for oxidation reactions, extraction, and chromatog-
raphy were reagent grade and used as received. Phenyl sulfide
compounds were prepared by the reaction of the corresponding
halides (either bromide or chloride) with benzenethiol in THF
in the presence of Et3N. Diallylic sulfide compounds were
prepared by the reaction of the corresponding allylic bromides
with Na2S‚9H2O in CH3OH. Column chromatography was
performed by the method of Still with silica gel 60, 230-400
mesh ASTM supplied by Merck. All reactions were performed
in an open system under air.
allylic sulfide 5 containing conjugated triene, which had
problems of low selectivity and low yield presumably due
to epoxidation with the other oxidants (Table 3). Selective
oxidations to sulfoxide 6 (80%) and to sulfone 7 (77%)
were achieved by using either 1 or 2.5 equiv of H2O2 at
0 °C or at room temperature, respectively. Once again,
the oxidation to sulfoxide 6 (80%) was accompanied by
further oxidation to sulfone 7 (4%) (entry 2, Table 4).
To establish the general applicability of LiNbMoO6
catalyst in chemoselective sulfur oxidation by H2O2,
various allylic sulfides with electron-rich double bonds,
together with benzylic and propargylic sulfides, were
used for the oxidation (Table 4). Thus, highly efficient
sulfur oxidations to sulfones were observed with LiNb-
MoO6 (0.05 mol %)-H2O2 (3 equiv) oxidant for phenyl
sulfides of allylic, benzyl, and propargyl groups. High
chemoselectivity was also observed for the oxidation to
sulfoxides, but formation of small amounts of sulfones
was unavoidable, even under carefully controlled reaction
conditions using 1 equiv of H2O2 at 0 °C. This chemose-
lective oxidation reaction was not hindered by the pres-
ence of various functional groups including hydroxy,
formyl, and ethers of tetrahydropyranyl (THP) or tert-
butyldimethylsilyl (TBDMS) groups (entries 4-7, Table
4). Yields of the oxidation products, however, dropped
significantly for diallylic sulfides 29 and 32 of prenyl and
geranyl, even though the chemoselectivity was still
maintained. This phenomenon was more prominent for
the oxidation to sulfoxide, which might be explained by
the possible rearrangements (either Pummerer17 or 2,3-
sigmatropic18) of the resulting allylic sulfoxides.
Oxid a tion of P h en yl P r en yl Su lfid e (1):19 P r ep a r a tion
of Su lfoxid e 2,20 Su lfon e 3,21 a n d Ep oxysu lfon e 4.22
By H2O2-AcOH Oxid a n t a t Room Tem p er a tu r e. To a
stirred solution of phenyl prenyl sulfide (1) (524 mg, 2.94
mmol) in AcOH (15 mL) at room temperature was added 30%
aqueous solution of H2O2 (1.00 g, 8.82 mmol). The mixture was
stirred vigorously at that temperature for 24 h and diluted
with ether (30 mL) and then with H2O (15 mL). The mixture
was washed with 1 M NaOH solution (15 mL), dried over
anhydrous Na2SO4, filtered, and concentrated under reduced
pressure. The crude product was purified by SiO2 flash column
(17) Russell, G. A.; Pecoraro, J . M. J . Org. Chem. 1979, 44, 3990-
3991.
(18) Evans, D. A.; Andrews, G. C. Acc. Chem. Res. 1974, 7, 147-
155.
(19) Harayama, H.; Kozera, T.; Mimura, M.; Tanaka, S.; Tamaru,
Y. Chem. Lett. 1996, 543-544.
(20) Uneyama, K.; Hasegawa, N.; Kawafuchi, H.; Torii, S. Bull.
Chem. Soc. J pn. 1983, 56, 1214-1218.
(21) J ulia, M.; Nel, M.; Uguen, D. Bull. Soc. Chim. Fr. 1987, 487-
492.
(22) Diggle, A. W.; Griffiths, G.; Young, D. J .; Stirling, C. J . M. Bull.
Soc. Chim. Fr. 1988, 317-321.

8196 J . Org. Chem., Vol. 66, No. 24, 2001
Choi et al.
chromatography to give rise to phenyl prenyl sulfoxide (2) (516
g, 2.65 mmol) in 90% yield as the sole product.
for 3 h gave sulfone 3 (172 mg, 0.82 mmol) in 82% yield as a
single product.
By H2O2-AcOH Oxid a n t a t 70 °C. The mixture of sulfide
1 (637 mg, 3.57 mmol) and 30% H2O2 solution (1.10 g, 10.7
mmol) in AcOH (18 mL) was heated to 70 °C for 3 h and then
cooled to room temperature. The resulting mixture was worked
up and purified as above to provide sulfoxide 2 (40 mg, 0.19
mmol), sulfone 3 (34 mg, 0.17 mmol), and epoxysulfone 4 (88
mg, 0.42 mmol) in 5%, 5%, and 12% yield, respectively.
Gen er a l Oxid a tion P r oced u r e of P h en yl P r en yl Su l-
fid e (1) by Oth er Electr op h ilic Oxid a n ts. To a stirred
solution of sulfide 1 in the selected solvent was added each
oxidant at 0 °C. After certain reaction time, the mixture was
diluted with CHCl3, washed with H2O, dried over anhydrous
Na2SO4, filtered, and concentrated under reduced pressure.
Sulfoxide 2 or sulfone 3 was obtained after purification by SiO2
flash chromatography.
By Oxon e. The reaction of sulfide 1 (178 mg, 1.00 mmol)
in CH3OH (5 mL) with Oxone (615 mg, 1.00 mmol) at room
temperature for 1 h gave sulfoxide 2 (104 mg, 0.54 mmol) and
sulfone 3 (32 mg, 0.15 mmol) in 54% and 15% yield, respec-
tively. When 3 equiv of Oxone (1.85 g, 3.00 mmol) was used
for the oxidation of sulfide 1 (178 mg, 1.00 mmol) at room
temperature for 6 h, sulfoxide 2 (78 mg, 0.40 mmol) and sulfone
3 (68 mg, 0.32 mmol) were obtained in 40% and 32% yield,
respectively.
By Na IO4. The reaction of sulfide 1 (178 mg, 1.00 mmol) in
CH3OH (5 mL) with NaIO4 (214 mg, 1.00 mmol) at 0 °C for 4
h and then at room temperature for another 4 h gave sulfoxide
2 (129 mg, 0.66 mmol) in 66% yield as a single product. When
3 equiv of NaIO4 (642 mg, 3.00 mmol) was used for the
oxidation of sulfide 1 (178 mg, 1.00 mmol) at room temperature
for 6 h, sulfoxide 2 (159 mg, 0.82 mmol) and sulfone 3 (5 mg,
0.02 mmol) were obtained in 82% and 2% yield, respectively.
By MCP BA. The reaction of sulfide 1 (178 mg, 1.00 mmol)
in CH2Cl2 (5 mL) with ∼70% MCPBA (247 mg, 1.00 mmol) at
0 °C for 4 h and then at room temperature for another 4 h
gave sulfoxide 2 (145 mg, 0.75 mmol) and sulfone 3 (4 mg,
0.04 mmol) in 75% and 4% yield, respectively. When 3 equiv
of ∼70% MCPBA (741 mg, 3.00 mmol) was used for the
oxidation of sulfide 1 (178 mg, 1.00 mmol) at room temperature
for 4 h, sulfone 3 (46 mg, 0.22 mmol) and epoxysulfone 4 (141
mg, 0.67 mmol) were obtained in 22% and 67% yield, respec-
tively.
Gen er a l P r oced u r e for Oxid a tion of Su lfid e 1 by Meta l
Oxid e Ca ta lyst-H2O2 Oxid a n t. To a stirred solution of
sulfide 1 (178 mg, 1.00 mmol) in CH3OH (5 mL) were
consecutively added metal oxide catalyst (0.05 mmol) and 30%
aqueous solution of H2O2 (1.00 or 3.00 mmol) at 0 °C (or at
room temperature). The reaction mixture was stirred at 0 °C
or at room temperature for the specified amounts of time. The
mixture was then concentrated under reduced pressure. The
crude product was then purified by SiO2 flash chromatography.
By MoO3. The reaction using MoO3 catalyst (7 mg, 0.05
mmol) and 1 equiv of 30% H2O2 (113 mg, 1.00 mmol) at room
temperature for 24 h gave sulfoxide 2 (124 mg, 0.64 mmol)
and sulfone 3 (41 mg, 0.20 mmol) in 64% and 20% yield,
respectively. While, use of 3 equiv of 30% H2O2 (339 mg, 3.00
mmol) at room temperature for 24 h gave sulfoxide 2 (120 mg,
0.62 mmol) and sulfone 3 (54 mg, 0.26 mmol) in 62% and 26%
yield, respectively.
By Na 2WO4. The reaction using Na2WO4 catalyst (17 mg,
0.05 mmol) and 1 equiv of 30% H2O2 (113 mg, 1.00 mmol) at
0 °C for 4 h and then room temperature for 1 h gave sulfoxide
2 (124 mg, 0.64 mmol) and sulfone 3 (48 mg, 0.23 mmol) in
64% and 23% yield, respectively. While, use of 3 equiv of 30%
H2O2 (339 mg, 3.00 mmol) at room temperature for 1 h gave
sulfone 3 (179 mg, 0.85 mmol) in 85% yield as a single product.
Oxid a tion of P h en yl 3,7,11-Tr im eth yl-2,4,6,10-d od ec-
a tetr a en yl Su lfid e (5): P r ep a r a tion of Su lfid e 6 or
Su lfon e 7. Gen er a l P r oced u r e for Oxid a tion of Su lfid e
5 by Meta l or Non m eta l Oxid e Ca ta lyst-H2O2 Oxid a n t.
To a stirred solution of sulfide 5 (67 mg, 0.20 mmol), a mixture
of stereoisomers (2.5:1, trans:cis at C-2) in CH3OH (1.5 mL)
and benzene (0.5 mL) were consecutively added the catalyst
(0.05 equiv, 0.01 mmol) and 1 equiv or 2 equiv of 30% aqueous
solution of H2O2 (0.20 or 0.40 mmol) at 0 °C or at room
temperature. The reaction mixture was stirred at 0 °C or at
room temperature for the specified amounts of time. The
mixture was then concentrated under reduced pressure. The
crude product was purified by SiO2 flash chromatography to
give sulfoxide 6 or sulfone 7. The stereoisomers (2.5:1, trans:
cis at C-2) were separable after oxidation to sulfone 7. In all
of the cases, an appreciable amount of side products that are
believed to be epoxidation products was obtained. These side
products were hardly separable and were not identified.
By Nb2O5. The reaction using Nb2O5 catalyst (3 mg, 0.01
mmol) and 1 equiv of 30% H2O2 (23 mg, 0.20 mmol) at room
temperature for 4 h gave sulfoxide 6 (21 mg, 0.06 mmol) and
sulfone 7 (10 mg, 0.028 mmol) in 30% and 14% yield,
respectively. While, use of 2 equiv of 30% H2O2 (46 mg, 0.40
mmol) at 0 °C for 2 h and then at room temperature for 22 h
gave sulfoxide 6 (12 mg, 0.034 mmol) and sulfone 7 (16 mg,
0.046 mmol) in 17% and 23% yield, respectively. Data for 6
(major trans isomer): 1H NMR δ 1.59 (3H, s), 1.63 (3H, s),
1.70 (3H, s), 1.81 (3H, s), 2.12 (4H, br s), 3.71 (1H, d of A of
ABq, J d ) 8.6, J AB ) 12.8 Hz), 3.78 (1H, d of B of ABq, J d
)
8.2, J AB ) 12.8 Hz), 5.13 (1H, br s), 5.29 (1H, t, J ) 8.4 Hz),
5.90 (1H, d, J ) 10.9 Hz), 6.14 (1H, d, J ) 15.2 Hz), 6.44 (1H,
dd, J ) 15.2, 10.9 Hz), 7.47-7.55 (3H, m), 7.57-7.65 (2H, m)
ppm; 13C NMR δ 12.5, 16.8, 17.6, 25.6, 26.5, 40.0, 57.2, 115.8,
123.7, 124.3, 124.8, 125.9, 128.0, 128.9, 131.0, 131.7, 133.5,
140.6, 142.5 ppm; IR (KBr) 1444, 1047 cm-1; HRMS (CI+) calcd
for C21H29OS 329.1939, found 329.1949. Data for 7 (trans at
C-2): 1H NMR δ 1.60 (3H, s), 1.68 (3H, s), 1.71 (3H, s), 1.78
(3H, s), 2.09 (4H, br s), 3.67 (2H, d, J ) 8.0 Hz), 5.10 (1H, br
s), 5.57 (1H, t, J ) 8.0 Hz), 5.89 (1H, d, J ) 11.0 Hz), 6.16
(1H, d, J ) 15.2 Hz), 6.40 (1H, dd, J ) 15.2, 11.0 Hz), 7.12-
7.44 (5H, m); 13C NMR δ 12.2, 16.8, 17.5, 25.5, 26.4, 39.9, 56.5,
114.7, 123.6, 124.7, 126.4, 128.3, 128.9, 131.6, 133.1, 133.5,
138.5, 140.9, 142.7 ppm; IR (KBr) 1307, 1151 cm-1; HRMS
(FAB+) calcd for C21H29O2S 345.1888, found 345.1893. Data
for 7 (cis at C-2) 1H NMR δ 1.60 (3H, s), 1.68 (3H, s), 1.79
(3H, s), 1.88 (3H, s), 2.10 (4H, br s), 3.73 (2H, d, J ) 7.9 Hz),
5.10 (1H, br s), 5.44 (1H, t, J ) 7.9 Hz), 5.93 (1H, d, J ) 11.5
Hz), 6.16 (1H, d, J ) 15.2 Hz), 6.47 (1H, dd, J ) 15.2, 11.0
Hz), 7.12-7.44 (5H, m) ppm; 13C NMR d16.9, 17.7, 20.6, 25.7,
26.5, 40.1, 55.5, 112.8, 123.7, 124.9, 125.1, 128.4, 128.9, 129.2,
131.7, 133.6, 138.6, 141.4, 141.6 ppm; IR (KBr) 1307, 1151
cm-1; HRMS (FAB+) calcd for C21H29O2S 345.1888, found
345.1893.
By MeReO3. The reaction using MeReO3 catalyst (12 mg,
0.05 mmol) and 1 equiv of 30% H2O2 (113 mg, 1.00 mmol) at
0 °C for 1 h gave sulfoxide 2 (136 mg, 0.70 mmol) and sulfone
3 (29 mg, 0.14 mmol) in 70% and 14% yield, respectively.
While, use of 3 equiv of 30% H2O2 (339 mg, 3.00 mmol) at room
temperature for 2 h gave sulfone 3 (59 mg, 0.28 mmol) and
epoxysulfone 4 (92 mg, 0.41 mmol) in 28% and 41% yield,
respectively.
By V2O5. The reaction using V2O5 catalyst (9 mg, 0.05 mmol)
and 1 equiv of 30% H2O2 (113 mg, 1.00 mmol) at 0 °C for 1 h
gave sulfoxide 2 (144 mg, 0.74 mmol) and sulfone 3 (27 mg,
0.13 mmol) in 74% and 13% yield, respectively. While, use of
3 equiv of 30% H2O2 (339 mg, 3.00 mmol) at room temperature
By MoO3. The reaction using MoO3 catalyst (1.4 mg, 0.01
mmol) and 1 equiv of 30% H2O2 (23 mg, 0.20 mmol) at room
temperature for 18 h gave sulfoxide 6 (18 mg, 0.05 mmol) and
sulfone 7 (4.3 mg, 0.012 mmol) in 25% and 6% yield, respec-
tively. While, use of 2 equiv of 30% H2O2 (46 mg, 0.40 mmol)
at 0 °C for 2 h and then at room temperature for 22 h gave
sulfoxide 6 (6.4 mg, 0.019 mmol) and sulfone 7 (10.4 mg, 0.030
mmol) in 9% and 15% yield, respectively.
By MeReO3. The reaction using MeReO3 catalyst (2.4 mg,
0.0096 mmol) and 1 equiv of 30% H2O2 (23 mg, 0.20 mmol) at
room temperature for 0.5 h gave sulfoxide 6 (19 mg, 0.056
mmol) and sulfone 7 (7.2 mg, 0.020 mmol) in 26% and 10%

Selective Oxidation of Allylic Sulfides
J . Org. Chem., Vol. 66, No. 24, 2001 8197
yield, respectively. While, use of 2 equiv of 30% H2O2 (46 mg,
0.40 mmol) at 0 °C for 0.5 h and then at room temperature for
0.5 h gave sulfoxide 6 (9.5 mg, 0.028 mmol) and sulfone 7 (10.4
mg, 0.030 mmol) in 14% and 15% yield, respectively.
By Na 2WO4. The reaction using Na2WO4 catalyst (3.4 mg,
0.010 mmol) and 1 equiv of 30% H2O2 (23 mg, 0.20 mmol) at
room temperature for 0.5 h gave sulfoxide 6 (30 mg, 0.09 mmol)
and sulfone 7 (19.3 mg, 0.055 mmol) in 43% and 27% yield,
respectively. While, use of 2 equiv of 30% H2O2 (46 mg, 0.40
mmol) at 0 °C for 1 h and then at room temperature for 1 h
gave sulfoxide 6 (21 mg, 0.063 mmol) and sulfone 7 (35 mg,
0.01 mmol) in 30% and 50% yield, respectively.
By V2O5. The reaction using V2O5 catalyst (2 mg, 0.01 mmol)
and 1 equiv of 30% H2O2 (23 mg, 0.20 mmol) at room
temperature for 1 h gave sulfoxide 6 (39 mg, 0.12 mmol) and
sulfone 7 (3 mg, 0.01 mmol) in 56% and 4% yield, respectively.
While, use of 2 equiv of 30% H2O2 (46 mg, 0.40 mmol) at 0 °C
for 2 h and then at room temperature for 2 h gave sulfoxide 6
(8 mg, 0.023 mmol) and sulfone 7 (6 mg, 0.02 mmol) in 11%
and 9% yield, respectively.
Oxid a tion of P h en yl 3,7,11-Tr im eth yl-2,4,6,10-d od ec-
a tetr a en yl Su lfid e (5): P r ep a r a tion of Su lfoxid e 6. Phen-
yl 3,7,11-trimethyl-2,4,6,10-dodecatetraenyl sulfide (5) having
trans/cis ratio (on the double bond of C-2) of about 2.5:1 (156
mg, 0.50 mmol) was reacted with LiNbMoO6 (7 mg, 0.025
mmol) and 34% aqueous H2O2 solution (50 µL, 0.50 mmol) in
a mixture of methanol (2.0 mL) and benzene (0.5 mL) at 0 °C
to room temperature for 2.5 h to give sulfoxide 6 having trans/
cis ratio (on the double bond of C-2) of about 2.5:1 (131 mg,
0.40 mmol, yield: 80%). Sulfone 7 (7 mg, 0.02 mmol, yield:
4%) was also obtained. P r ep a r a tion of Su lfon e 7. Phenyl
3,7,11-trimethyl-2,4,6,10-dodecatetraenyl sulfide (5) having
trans/cis ratio (on the double bond of C-2) of about 2.5:1 (16 g,
51.5 mmol) was reacted with LiNbMoO6 (301 mg, 1.03 mmol)
and 35% aqueous H2O2 solution (12.5 g, 0.13 mol) in a mixture
of benzene (30 mL) and methanol (70 mL) at 0 °C to 25 °C for
6 h to give sulfone 7 (13.7 g, 39.8 mmol, yield: 77%). The
sulfone had trans/cis ratio (on the double bond of C-2) of about
2.5:1, and the trans- and cis-isomers were separated by column
chromatography.
Oxid a tion of Ger a n yl P h en yl Su lfid e (8):23 P r ep a r a -
tion of Su lfoxid e 9.24 Geranyl phenyl sulfide (8) (123 mg,
0.50 mmol) was reacted with LiNbMoO6 (7 mg, 0.05 mmol)
and 34% aqueous H2O2 solution (50 mg, 0.50 mmol) in
methanol (2.5 mL) at 0 °C for 1 h to give sulfoxide 9 (102 mg,
0.39 mmol, yield: 78%). Sulfone 10 (19 mg, 0.07 mmol, yield:
14%) was also obtained. P r ep a r a tion of Su lfon e 10.25
Geranyl phenyl sulfide (8) (2.80 g, 11.4 mmol) was reacted with
LiNbMoO6 (0.17 g, 0.60 mmol) and 30% aqueous H2O2 solution
(3.86 g, 34.1 mmol) in methanol (45 mL) at room temperature
for 4 h to give sulfone 10 (2.68 g, 9.60 mmol, yield: 85%).
Oxid a tion of 4-Hyd r oxy-3-m eth yl-2-bu ten yl P h en yl
Su lfid e (11):26 P r ep a r a tion of Su lfoxid e 12.27 4-Hydroxy-
prenyl phenyl sulfide (11) (97 mg, 0.50 mmol) was reacted with
LiNbMoO6 (7 mg, 0.05 mmol) and 34% aqueous H2O2 solution
(50 mg, 0.50 mmol) in methanol (2.5 mL) at 0 °C for 1 h to
give sulfoxide 12 (79 mg, 0.38 mmol, yield: 75%). At the same
time, sulfone 13 (14 mg, 0.06 mmol, yield: 12%) was also
obtained. P r ep a r a tion of Su lfon e 13. 4-Hydroxyprenyl
phenyl sulfide (11) (600 mg, 3.20 mmol) was reacted with
LiNbMoO6 (46 mg, 0.20 mmol) and 30% aqueous H2O2 solution
(960 mg, 9.50 mmol) in methanol (15 mL) at room temperature
for 4 h to give sulfone 13 (670 mg, 3.00 mmol, yield: 95%).
Data for 13: 1H NMR δ 1.34 (3H, s), 2.92 (1H, br s), 3.86 (2H,
d, J ) 8.1 Hz), 3.96 (2H, s), 5.52 (1H, t, J ) 8.1 Hz), 7.31-
7.89 (5H, m) ppm; 13C NMR δ 13.4, 55.4, 66.9, 109.5, 128.1,
129.6, 133.7, 138.2, 145.6 ppm; IR (KBr) 3511, 1447, 1304,
1149 cm-1; HRMS (CI+) calcd for C11H15O3S 227.0743, found
227.0749.
Oxid a tion of 4-F or m yl-3-m eth yl-2-bu ten yl P h en yl Su l-
fid e (14):28 P r ep a r a tion of Su lfoxid e 15. Formylprenyl
phenyl sulfide 14 (192 mg, 1.00 mmol) was reacted with
LiNbMoO6 (15 mg, 0.10 mmol) and 35% aqueous H2O2 solution
(98 mg, 1.00 mmol) in methanol (5 mL) at 0 °C for 5 h to give
sulfoxide 15 (175 mg, 0.84 mmol, yield: 84%). At the same
time, sulfone 16 (23 mg, 0.10 mmol, yield: 10%) was also
obtained. P r ep a r a tion of Su lfon e 16.29 Formylprenyl phenyl
sulfide 14 (192 mg, 1.00 mmol) was reacted with LiNbMoO6
(15 mg, 0.10 mmol) and 35% aqueous H2O2 solution (294 mg,
3.00 mmol) in methanol (5 mL) at room temperature for 18 h
to give sulfone 16 (184 mg, 0.82 mmol, yield: 82%). In these
By SeO2. The reaction using SeO2 catalyst (1 mg, 0.01
mmol) and 1 equiv of 30% H2O2 (23 mg, 0.20 mmol) at room
temperature for 18 h gave sulfoxide 6 (18 mg, 0.054 mmol) in
26% yield. While, use of 2 equiv of 30% H2O2 (46 mg, 0.40
mmol) at 0 °C for 2 h and then at room temperature for 22 h
gave sulfoxide 6 (7 mg, 0.021 mmol) and sulfone 7 (8 mg, 0.024
mmol) in 10% and 12% yield, respectively.
By TP AP /NMO. The oxidation of sulfide 5 (156 mg, 0.50
mmol) using TPAP catalyst (9 mg, 0.025 mmol) and 1 equiv
of NMO (59 mg, 0.50 mmol) oxidant in CH3CN (2.5 mL) with
4 Å molecular sieve (50 mg) at 40 °C for 22 h gave sulfoxide 6
(7 mg, 0.02 mmol) and sulfone 7 (12 mg, 0.035 mmol) in 4%
and 7% yield, respectively, while use of 2 equiv of NMO (117
mg, 1.00 mmol) oxidant at 40 °C for 22 h gave sulfoxide 6 (17
mg, 0.05 mmol) and sulfone 7 (20 mg, 0.06 mmol) in 10% and
12% yield, respectively.
By MCP BA. The reaction of sulfide 5 (67 mg, 0.20 mmol)
in CH2Cl2 (2 mL) with ∼70% MCPBA (49 mg, 0.20 mmol) at
room temperature for 1 h gave sulfoxide 6 (56 mg, 0.17 mmol)
and sulfone 7 (1.4 mg, 0.004 mmol) in 79% and 2% yield,
respectively, while use of 2 equiv of ∼70% MCPBA (98 mg,
0.40 mmol) at 0 °C for 0.5 h and then room temperature for
0.5 h gave sulfoxide 6 (15 mg, 0.044 mmol) and sulfone 7 (25
mg, 0.07 mmol) in 21% and 35% yield, respectively.
Gen er a l P r oced u r e for Ch em oselective Oxid a tion of
Va r iou s Su lfid es by LiNbMoO6 Ca ta lyst-H2O2 Oxid a n t:
To Su lfoxid es. To a stirred solution of allylic sulfide (1 equiv)
in methanol (and benzene in some cases) at 0 °C were added
LiNbMoO6 (0.05 equiv) and ∼30% aqueous solution of hydro-
gen peroxide (1 equiv). After stirring the resultant mixture at
0 °C for a specified amount of time, the solvent was removed
by evaporation under reduced pressure. Thus obtained crude
product was purified by silica gel column chromatography to
give allylic sulfoxide. Small amount of allylic sulfone was also
obtained. To Su lfon es. To a stirred solution of allylic sulfide
(1 equiv) in methanol (and benzene in some cases) at 0 °C were
added LiNbMoO6 (0.05 equiv) and ∼30% aqueous solution of
hydrogen peroxide (3 equiv). After stirring the resultant
mixture at room temperature for a specified duration, chloro-
form was added, and the mixture was well washed with
distilled water, dried over anhydrous Na2SO4, and filtered.
After removing the solvent under reduced pressure, the crude
product was purified by silica gel column chromatography to
give allylic sulfones.
Oxid a tion of P h en yl P r en yl Su lfid e (1): P r ep a r a tion
of Su lfoxid e 2. Phenyl prenyl sulfide (1) (0.71 g, 4.00 mmol)
was reacted with LiNbMoO6 (58 mg, 0.20 mmol) and 30%
aqueous H2O2 solution (454 mg, 4.00 mmol) in CH3OH (20 mL)
at 0 °C for 4 h to give sulfoxide 2 (0.60 g, 3.10 mmol, yield:
77%). Sulfone 3 (0.12 g, yield: 14%) was also obtained.
P r ep a r a tion of Su lfon e 3. Phenyl prenyl sulfide (1) (0.60 g,
3.30 mmol) was reacted with LiNbMoO6 (49 mg, 0.20 mmol)
and 30% aqueous H2O2 solution (1.13 g, 10.0 mmol) in CH3-
OH (20 mL) at room temperature for 4 h to give sulfone 3 (0.56
g, 2.70 mmol, yield: 82%).
(23) Cookson, R. C.; Parsons, P. J . J . Chem. Soc., Chem. Commun.
1978, 822-824.
(24) Breton, G. W.; Fields, J . D.; Kropp, P. J . Tetrahedron Lett. 1995,
36, 3525-3528.
(25) J ulia, M.; Righini, A.; Verpeaux, J . N. Tetrahedron Lett. 1979,
2393-2396.
(26) Martin, G.; Sauleau, J .; David, M.; Sauleau, A.; Sinbandhit, S.
Can. J . Chem. 1992, 70, 2190-2196.
(27) Mandai, T.; Yokoyama, H.; Miki, T.; Fukuda, H.; Kobata, H.;
Kawada, M.; Otera, J . Chem. Lett. 1980, 1057-1060.
(28) Matsumoto, M.; Ito, S. J . Chem. Soc., Chem. Commun. 1981,
907-908.
(29) Sato, T.; Hanayama, K.; Fujisawa, T. Tetrahedron Lett. 1988,
29, 2197-2200.

8198 J . Org. Chem., Vol. 66, No. 24, 2001
Choi et al.
cases, acid workup was required to convert some acetal formed
by the reaction with MeOH into the formyl group again. Data
mmol) was reacted with LiNbMoO6 (7.3 mg, 0.05 mmol) and
34% aqueous H2O2 solution (50 mg, 0.50 mmol) in methanol
(2.5 mL) at 0 °C for 1 h to give sulfoxide 24 (102 mg, 0.47 mmol,
yield: 94%). Sulfone 25 (3 mg, 0.01 mmol, yield: 3%) was also
obtained. P r ep a r a tion of Su lfon e 25.32 Benzyl phenyl sulfide
(23) (2.00 g, 10.0 mmol) was reacted with LiNbMoO6 (0.15 mg,
0.50 mmol) and 30% aqueous H2O2 solution (3.40 g, 30.0 mmol)
in methanol (50 mL) at room temperature for 4 h to give
sulfone 25 (2.27 g, 9.80 mmol, yield: 98%).
for 15: 1H NMR δ 1.39 (3H, s), 3.65 (1H, d of A of ABq, J d
8.4, J AB ) 13.1 Hz), 3.87 (1H, d of B of ABq, J d ) 7.7, J AB
)
)
13.1 Hz), 6.28 (1H, dd, J ) 7.7, 8.4 Hz), 7.38-7.50 (5H, m),
9.26 (1H, s) ppm; 13C NMR δ 9.1, 55.2, 123.6, 128.9, 131.1,
138.0, 142.0, 144.7, 193.3 ppm; IR (KBr) 1688, 1443, 1307 cm-1
HRMS (CI+) calcd for C11H13O2S 209.0636, found 209.0635.
;
Oxid a tion of 4-Hyd r oxy-3-m eth yl-2-bu ten yl P h en yl
Su lfid e, Tetr a h yd r op yr a n yl Eth er (17). P r ep a r a tion of
Su lfoxid e 18. THP ether of hydroxyprenyl phenyl sulfide 17
(278 mg, 1.00 mmol) was reacted with LiNbMoO6 (15 mg, 0.10
mmol) and 35% aqueous H2O2 solution (98 mg, 1.00 mmol) in
methanol (5 mL) at 0 °C for 3 h to give sulfoxide 18 (241 mg,
0.82 mmol, yield: 82%). At the same time, sulfone 19 (37 mg,
0.12 mmol, yield: 12%) was also obtained. P r ep a r a tion of
Su lfon e 19. THP ether of hydroxyprenyl phenyl sulfide 17
(278 mg, 1.00 mmol) was reacted with LiNbMoO6 (15 mg, 0.10
mmol) and 35% aqueous H2O2 solution (294 mg, 3.00 mmol)
in methanol (5 mL) at room temperature for 18 h to give
sulfone 19 (264 mg, 0.85 mmol, yield: 85%). Data for 18: 1H
NMR δ 1.45 (3H, s), 1.44-1.86 (6H, m), 3.43-3.54 (1H, m),
3.62 (2H, d, J ) 8.1 Hz), 3.75-3.89 (1H, m), 3.84 (1H, A of
ABq, J AB ) 13.0 Hz), 4.07 (1H, B of ABq, J AB ) 13.0 Hz), 4.55
(1H, dt, J d ) 3.5, J t ) 3.4 Hz), 5.39 (1H, t, J ) 8.1 Hz), 7.39-
7.86 (5H, m) ppm; 13C NMR δ 13.8, 18.9, 25.0, 30.1, 55.5, 61.6,
70.9, 97.2, 112.1, 124.0, 128.5, 130.6, 141.6, 142.9 ppm; IR
(KBr) 1443, 1037 cm-1; HRMS (CI+) calcd for C16H23O3S
295.1368, found 295.1371. Data for 19: 1H NMR δ 1.36 (3H,
s), 1.45-1.86 (6H, m), 3.45-3.55 (1H, m), 3.70-3.84 (1H, m),
3.83 (1H, A of ABq, J AB ) 13.6 Hz), 3.87 (2H, d, J ) 8.0 Hz),
4.06 (1H, B of ABq, J AB ) 13.6 Hz), 4.54 (1H, dd, J ) 3.5, 3.1
Hz), 5.50 (1H, t, J ) 8.0 Hz), 7.48-7.89 (5H, m) ppm; 13C NMR
δ 13.7, 19.1, 25.2, 30.3, 55.5, 61.9, 70.8, 97.5, 111.6, 128.2,
Oxid a tion of P h en yl P r op a r gyl Su lfid e (26): 33 P r ep a -
r a tion of Su lfoxid e 27.34 Phenyl propargyl sulfide (26) (74
mg, 0.50 mmol) was reacted with LiNbMoO6 (7.3 mg, 0.05
mmol) and 34% aqueous H2O2 solution (50 mg, 0.50 mmol) in
methanol (2.5 mL) at 0 °C for 1 h to give sulfoxide 27 (76 mg,
0.46 mmol, yield: 93%). Sulfone 28 (5 mg, 0.03 mmol, yield:
6%) was also obtained. P r ep a r a tion of Su lfon e 28.35 Phenyl
propargyl sulfide (26) (1.58 g, 10.7 mmol) was reacted with
LiNbMoO6 (0.16 g, 0.50 mmol) and 30% aqueous H2O2 solution
(3.60 g, 32.0 mmol) in methanol (50 mL) at room temperature
for 4 h to give sulfone 28 (1.62 g, 9.00 mmol, yield: 84%).
Oxid a tion of Dip r en yl Su lfid e (29):36 P r ep a r a tion of
Su lfoxid e 30.37 Diprenyl sulfide (29) (85 mg, 0.50 mmol) was
reacted with LiNbMoO6 (7.3 mg, 0.05 mmol) and 34% aqueous
H2O2 solution (50 mg, 0.50 mmol) in methanol (2.5 mL) at 0
°C for 1 h to give sulfoxide 30 (50 mg, 0.27 mmol, yield: 54%).
Sulfone 31 (108 mg, 0.53 mmol, yield: 6%) was also obtained.
P r ep a r a tion of Su lfon e 31.38 Diprenyl sulfide (29) (0.60 g,
3.50 mmol) was reacted with LiNbMoO6 (51 mg, 0.20 mmol)
and 30% aqueous H2O2 solution (1.00 g, 10.1 mmol) in
methanol (18 mL) at room temperature for 4 h to give sulfone
31 (0.43 g, 2.10 mmol, yield: 71%).
Oxid a tion of Diger a n yl Su lfid e (32):39 P r ep a r a tion of
Su lfoxid e 33.40 Digeranyl sulfide (32) (153 mg, 0.50 mmol)
was reacted with LiNbMoO6 (7.3 mg, 0.05 mmol) and 34%
aqueous H2O2 solution (50 mg, 0.50 mmol) in methanol (2.5
mL) at 0 °C for 1 h to give sulfoxide 33 (77 mg, 0.24 mmol,
yield: 48%). Sulfone 34 (12 mg, 0.04 mmol, yield: 7%) was
also obtained. P r ep a r a tion of Su lfon e 34.38 Digeranyl sulfide
(32) (3.57 g, 11.7 mmol) was reacted with LiNbMoO6 (0.17 g,
0.60 mmol) and 30% aqueous H2O2 solution (3.96 g, 35.0 mmol)
in methanol (40 mL) at room temperature for 4 h to give
sulfone 34 (2.84 g, 8.40 mmol, yield: 72%).
128.9, 133.5, 138.4, 142.5 ppm; IR (KBr) 1447, 1307, 1152 cm-1
HRMS (CI+) calcd for C16H23O4S 311.1317, found 311.1317.
;
Oxid a tion of 4-Hyd r oxy-3-m eth yl-2-bu ten yl P h en yl
Su lfid e, ter t-Bu tyld im eth ylsilyl Eth er (20): P r ep a r a tion
of Su lfoxid e 21. TBDMS ether of hydroxyprenyl phenyl
sulfide 20 (309 mg, 1.00 mmol) was reacted with LiNbMoO6
(15 mg, 0.10 mmol) and 35% aqueous H2O2 solution (98 mg,
1.00 mmol) in methanol (5 mL) at 0 °C for 3 h to give sulfoxide
21 (260 mg, 0.80 mmol, yield: 80%). At the same time, sulfone
22 (31 mg, 0.09 mmol, yield: 9%) was also obtained. P r ep a r a -
tion of Su lfon e 22. TBDMS ether of hydroxyprenyl phenyl
sulfide 20 (309 mg, 1.00 mmol) was reacted with LiNbMoO6
(15 mg, 0.10 mmol) and 35% aqueous H2O2 solution (294 mg,
3.00 mmol) in methanol (5 mL) at room temperature for 18 h
to give sulfone 22 (272 mg, 0.80 mmol, yield: 80%). Data for
21: 1H NMR δ 0.03 (6H, s), 0.89 (9H, s), 1.42 (3H, s), 3.58
(1H, d of A of ABq, J d ) 8.4, J AB ) 12.5 Hz), 3.66 (1H, d of B
of ABq, J d ) 8.4, J AB ) 12.5 Hz), 3.99 (2H, s), 5.35 (1H, t, J )
8.4 Hz), 7.47-7.63 (5H, m) ppm; 13C NMR δ -5.6, 13.5, 18.1,
25.7, 55.8, 67.0, 109.5, 124.3, 128.7, 130.8, 143.1, 144.1 ppm;
IR (KBr) 1443, 1048 cm-1; HRMS (CI+) calcd for C17H29O2SSi
Ack n ow led gm en t. This work was supported by the
RRC program of MOST and KOSEF.
J O016013S
(30) Lu, G.; Zhang, Y. Synth. Commun. 1998, 28, 4479-4484.
(31) Kropp, P. J .; Breton, G. W.; Fields, J . D.; Tung, J . C.; Loomis,
B. R. J . Am. Chem. Soc. 2000, 122, 4280-4285.
(32) Balicki, R. Synth. Commun. 1999, 29, 2235-2239.
(33) Luo, F.-T.; Ko, S.-L.; Liu, L.; Chen, H. Heterocycles 2000, 53,
2055-2066.
(34) Skatteboel, L.; Boulette, B.; Solomon, S. J . Org. Chem. 1967,
32, 3111-3113.
1
325.1657, found 325.1662. Data for 22: H NMR δ 0.04 (6H,
(35) Pourcelot, G.; Cadiot, P. Bull. Soc. Chim. Fr. 1966, 3024-3033.
(36) Takabe, K.; Katagiri, T.; Tanaka, J . Tetrahedron Lett. 1971,
1503-1506.
s), 0.89 (9H, s), 1.56 (3H, s), 3.85 (2H, d, J ) 8.2 Hz), 3.96
(2H, s), 5.35 (1H, t, J ) 8.2 Hz), 7.43-7.93 (5H, m) ppm; 13C
NMR δ -5.6, 13.2, 18.1, 25.7, 55.4, 66.8, 109.0, 128.3, 128.8,
(37) Yang, W.; Liang, S.; J in, S. Huadong Huagong Xueyuan Xuebao
1987, 13, 760-763.
133.4, 138.5, 144.7 ppm; IR (KBr) 1447, 1307, 1152 cm-1
;
(38) Buechi, G.; Freidinger, R. M. J . Am. Chem. Soc. 1974, 96, 3332-
HRMS (CI+) calcd for C17H29O4SSi 341.1606, found 341.1607.
Oxid a tion of Ben zyl P h en yl Su lfid e (23):30 P r ep a r a tion
of Su lfoxid e 24.31 Benzyl phenyl sulfide (23) (100 mg, 0.50
3333.
(39) Baldwin, J . E.; Kelly, D. P. Chem. Commun. 1968, 899-900.
(40) Mantegani, A.; Bonardi, G. Chim. Ther. 1972, 7, 411-413.