(S)-dimethylsulfonium(p-tolylsulfinyl)methylide: A new chiral sulfonium ylide and its use in asymmetric epoxidation

Article abstract of DOI:10.1055/s-2006-933131

The title optically active sulfonium ylide was prepared by methylation of easily available (-)-(S)-p-tolylmethylthiomethyl-sulfoxide and subsequent deprotonation. Its reaction with aldehydes gave α,β-epoxy sulfoxides with full enantioselectivity and moder

Full text of DOI:10.1055/s-2006-933131

LETTER
733
(S)-Dimethylsulfonium(p-tolylsulfinyl)methylide: A New Chiral Sulfonium
Ylide and its Use in Asymmetric Epoxidation
A
N
ew Chiral Sulfonium
a
Y
lide and
n
its
U
se in A
d
symmetric
E
a
poxidation H. Midura*
Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Department of Heteroorganic Chemistry, Sienkiewicza
112, 90-363 Łódź, Poland
Fax +48(42)6847126; E-mail: whmidura@bilbo.cbmm.lodz.pl
Received 13 December 2005
Generally, the asymmetric conversions of aldehydes into
Abstract: The title optically active sulfonium ylide was prepared
oxiranes were mediated by sulfur ylides in which chirality
was located in the sulfonium moiety. Continuing our work
by methylation of easily available (–)-(S)-p-tolylmethylthiomethyl-
sulfoxide and subsequent deprotonation. Its reaction with aldehydes
gave a,b-epoxy sulfoxides with full enantioselectivity and moderate
on utilization of optically active sulfinyl compounds in
diastereoselectivity. The steric course of acid-catalyzed rearrange- asymmetric synthesis,7 we decided to design a new type of
ment of sulfinyl oxiranes is briefly discussed.
a chiral sulfur ylide containing optically active sulfinyl
group bonded to the ylidic carbon atom. Such a structure
represents a new chiral reagent for asymmetric epoxida-
tion and cyclopropanation. These reactions should result
in the formation of the corresponding products containing
the chiral sulfinyl auxiliary. Its presence may be utilized
for the separation of diastereomers; afterwards sulfinyl
group can be easily removed.
Key words: asymmetric synthesis, chiral auxiliaries, ylides, epoxi-
dation, sulfoxides
The sulfur ylides are a well-known class of compounds
that have been used as alkylidene transfer agents since the
early works of Johnson1 and Corey.2 The potential of sul-
fur ylides for the preparation of optically active epoxides
and cyclopropanes was first recognized and investigated
by Trost3 in 1973. However, the first nonracemic epoxida-
tion using aromatic aldehydes and chiral sulfur ylides was
reported by Furukawa in 1989.4 This strategy was effec-
tively developed by Metzner5 and Aggarwal.6 The use of
various chiral sulfides has been investigated for either
one-pot reaction or two-step procedure with pre-isolation
of the sulfonium salt. High level of diastereo- and enantio-
control was observed in the asymmetric epoxidation using
C2-symmetric 2,5-disubstituted tetrahydrothiophenes5,6
and especially oxathiane derived ylides as well as the
ylide based on bridged bicyclic sulfides applied by
Aggarwal in a catalytic protocol.6c
The sulfonium salt 2 required for the generation of the title
ylide 1 was obtained by methylation of (–)-(S)-p-tolyl
methylthiomethyl sulfoxide (3) with methyl iodide in the
presence of equimolar amount of silver tetrafluoroborate
in dry diethyl ether, followed by addition of acetone–wa-
ter 1:1 mixture, filtration of precipitated AgI and evapora-
tion of solvents (Scheme 1). The crystalline salt 2 formed
in quantitative yield was fully characterized.8 The starting
enantiopure thioacetal monosulfoxide 3 was prepared by
treatment of enantiopure (+)-(S)-bromomethyl p-tolyl-
sulfoxide with sodium methanethiolate9 or preferably by
the substitution of (–)-menthyl (–)-(S)-p-toluenesulfinate
with methylthiomethyllithium as described by Gennari.10
O
O
Me
–
a
+
S
BF4
S
S
:
p-Tol
75%
Me
p-Tol
:
OMen
(S)-2
[α]D = –202.9 (c 1.3, acetone)
c
O
[α]D = +285.9 (c 1.2, acetone)
100%
S
S
p-Tol
Me
d
100%
:
O
S
(S)-3
b
Br
p-Tol
[α]D = +193.3 (c 0.9, acetone)
O
S
60%
Me
S +
Me
:
p-Tol
–
[α]D = +153 (c 0.6, acetone)
:
(S)-1
Scheme 1 Reagents and conditions: (a) MeSCH2Li, TMEDA–THF, –78 °C; (b) MeSNa, MeCN–H2O, 2 h, r.t.; (c) MeI–AgBF4, overnight,
r.t.; (d) NaH, DMSO or MeCN, 1 h, r.t.
SYNLETT 2006, No. 5, pp 0733–0736
1
7.
0
3.
2
0
0
6
Advanced online publication: 09.03.2006
DOI: 10.1055/s-2006-933131; Art ID: G38405ST
© Georg Thieme Verlag Stuttgart · New York

734
W. H. Midura
LETTER
Treatment of the sulfonium salt 2 with sodium hydride in by assuming the same stereochemical course for epox-
DMSO solution at room temperature afforded dimethyl- idation of other aldehydes one can assign the 2S,3S-con-
sulfonium p-tolylsulfinylmethylide 1 in quantitative figuration for trans-4b and 4c and 2S,3R for cis-4b and 4c.
1
yield, as evidenced by H NMR.11 We have found that Unequivocal evidence confirming our configurational as-
generation of ylide 1 can be performed in acetonitrile signments was provided by the desulfinylation reactions
solution as well.
of resulting oxiranes 4. For example, desulfinylation of
trans-4b performed by methyllithium at –100 °C for one
minute, gave enantiopure16 dextrorotatory p-bromo-
styrene oxide 5b (Scheme 3), which has been recently ob-
tained by enzymatic resolution.17 It is interesting to point
out that combination of the asymmetric epoxidation using
the sulfinyl ylide 1 and desulfinylation reaction represents
a new approach to enantiopure monosubstituted oxiranes.
To demonstrate the utility of the sulfinylmethylide 1 in
asymmetric synthesis, we first applied it for the conver-
sion of aldehydes to epoxides. a,b-Epoxy sulfoxides have
been prepared earlier in Darzens-type procedure by reac-
tion of a-chloro sulfoxides with carbonyl compounds.12
An asymmetric version of this approach was developed by
Satoh.13 In this context, the use of ylide 1 offered an alter-
native route leading to these types of compounds. Thus,
the ylide 1 was in situ treated with benzaldehyde affording
3-phenyl-2-(p-tolylsulfinyl)oxirane (4a) as a mixture of
only two isomers in the 1.6:1 ratio. Since epoxides of this
structure are sensitive to acidic conditions and readily un-
dergo rearrangement to the appropriate aldehydes,12c puri-
fication of a,b-epoxysulfoxide 4a was performed by
chromatography on basic alumina, which allowed to sep-
arate both trans and cis isomers. Based on the NMR cou-
pling constants the trans-geometry was assigned to the
predominant isomer having 3JH–H = 1.6 Hz and cis to the
O
O
MeLi/THF
–100 °C, 1 min
87%
p-Br-C6H4
p-Br-C6H4
SO(p-Tol)
(R)-5b
(2S,3S,SS)-4b
[α]D= –13.0 (c 0.2, acetone)
[α]D= +52.1 (c 0.6, acetone)
Scheme 3
At this point it is necessary to underline a full enantio-
selectivity observed during the addition of the ylide 1 to
the carbonyl group. This means that the stereochemistry
on the ylidic carbon (C-2 in oxirane) is completely
controlled by the chirality of the sulfinyl center. It can be
explained by making assumption that ylide 1 adopts con-
formation, which determines the stereochemical course of
the reaction. According to the literature data,18 the most
stable conformation of sulfonium ylide is that, in which
the filled p-orbital on carbon is perpendicular to the lone
pair on sulfur. Conformation A for ylide 1 seems to fulfill
these requirements for both, sulfonium and sulfinyl, sulfur
atoms. The polar sulfinyl group can stabilize positive
charge on the neighboring sufonium sulfur atom and also
causes a rather transoid approach of the aldehyde, to
avoid dipole–dipole interaction between sulfinyl and
carbonyl groups. However, this hypothesis must be
verified (Scheme 4).
3
minor one with JH–H = 3.4 Hz. Using the same
procedure14 for other aryl (p-Br-C6H4CHO) and alkyl
(C9H19CHO) aldehydes, the corresponding a,b-epoxy-
sulfoxides 4b and 4c were obtained in a good yield
(Scheme 2). In the case of 4b, the trans and cis isomers
were formed in the 1.5:1 ratio, which could be slightly im-
proved, when the reaction was carried out in acetonitrile
solution (2.5:1 ratio). Both trans and cis isomers of 4c
were formed in almost equal amounts independently on
the solvent used.
O
S
O
Me
+
RCHO
solvent, r.t.
R
O
S
p-Tol
–
Me
R
SO(p-Tol)
SO(p-Tol)
cis-4
(S)-1
trans-4
trans/cis ratioi
yield
solvent
a: R = Ph
DMSO
MeCN
DMSO
MECN
DMSO
1.6
2.7
1.5
2.5
–1
:
:
:
:
:
1
1
1
1
1
81%
78%
82%
87%
75%
b: R = p-Br-C6H4
c: R = C9H19
Scheme 2 Determined by 1H NMR of the crude product.
Enantio- and diastereomerically pure 3-phenyl-2-(p-tolyl-
sulfinyl)oxiranes have been recently obtained by de la
Pradilla in the stereoselective nucleophilic epoxidation of
optically active a,b-unsaturated sulfoxides.15 Comparison
of their spectral and optical features presented in his paper
with our data of 3-phenyl-2-(p-tolylsulfinyl)oxiranes (4a)
confirmed formation of only two diastereomers in our
case and allowed us to assign the 2S,3S configuration for
trans-4a and 2S,3R for cis-4a. It can be concluded that
oxiranes formed using sulfonium ylide 1 are those, which
are minor products, obtained by de la Pradilla. Moreover,
Scheme 4
As we mentioned before, sulfinyl oxiranes easily undergo
acid-catalyzed rearrangement to a-sulfinylaldehydes.
This reaction was studied earlier12 on racemic epoxides.
However, because only one of each possible cis-trans
pairs of epoxides was available, the stereochemical course
of this rearrangement was unknown. Having both optical-
ly active cis and trans isomers of a,b-epoxysulfoxides 4
we made an attempt to solve this problem. Thus, treatment
Synlett 2006, No. 5, 733–736 © Thieme Stuttgart · New York

LETTER
A New Chiral Sulfonium Ylide and its Use in Asymmetric Epoxidation
735
atmosphere and mixture was cooled to 0 °C. Next, 0.65 g of
AgBF4 was added in small portions and vigorous stirring.
The temperature was maintained for 0.5 h, then 5 mL of Et2O
was added and stirring was continued at r.t. overnight. After
evaporation of Et2O the residue was treated with 20 mL of
H2O–acetone mixture (1:1) and filtrated. Then, acetone was
evaporated, water solution was extracted with 2 × 3 mL of
CHCl3 to remove impurities, and H2O was evaporated
of cis-(2S,3R,SS)-(p-bromophenyl)-2-(p-tolylsulfinyl)ox-
irane (4b, Scheme 5) with BF3 etherate for five minutes at
0 °C gave one diastereomer of p-bromophenyl(p-tolyl-
sulfinyl)acetaldehyde (6b, dH = 9.86 ppm for aldehyde
proton), which is configurationally stable. On the contrary
trans-2S,3S,SS-4b rearranges to the second diastereomer
of the aldehyde 6b (dH = 9.93 ppm for aldehyde proton),
which is unstable and easily undergoes isomerization to
its epimer.19 Such a stereochemical outcome of the reac-
tion under discussion suggests concerted mechanism of
the migration of the sulfinyl group.20 The oxirane 4c with
alkyl substituent does not undergo rearrangement so easi-
ly. Treatment with BF3·OEt2 for four hours at room tem-
perature leads to full conversion of cis-4c to unsaturated
aldehyde. However, trans-4c remains unchanged under
these conditions, so in this way it can be separated by
kinetic resolution.
22
affording 9 g of crystalline salt 2; mp 114–116 °C, [a]D
–285.9 (c 1.2, acetone). 1H NMR (200 MHz, CD3COCD3):
d = 2.43 (3 H, s, CH3PhS), 3.05 (3 H, s, CH3S), 3.16 (3 H, s,
CH3S), 4.83 and 5.10 (2 H, AB system, J = 13.2 Hz,
SCH2S), 7.49 and 7.73 (4 H, AB system J = 8.4 Hz, Ar). 13
NMR (50 MHz): d = 22.0, 27.3, 27.5, 64.0, 126.0, 131.9,
C
139.3, 144.9. Anal. Calcd for C10H15BF4OS2: C, 39.75; H,
5.00. Found: C, 39.64; H, 4.96.
(9) Numata, T.; Oae, S. Bull. Chem. Soc. Jpn. 1972, 45, 2794.
(10) Colombo, L.; Gennari, C.; Narisano, E. Tetrahedron Lett.
1978, 40, 3861.
(11) 1H NMR (200 MHz) spectrum of the ylide 1 generated in
DMSO-d6 showed signals at d = 2.32 (3 H, s, CH3Ph), 2.57
(3 H, s, CH3S), 2.62 (3 H, s, CH3S), 3.04 (1 H, SCHS), 7.23
and 7.44 (4 H, aromatic).
H
O
O
p-Br–Ph
p-Br–Ph
H
BF3·OEt2, CH2Cl2
*
*
*
TolS
0 °C, 5 min
H
(12) (a) Tavares, D. F.; Estep, R. E.; Blezard, M. Tetrahedron
Lett. 1970, 2373. (b) Durst, T.; Tin, K.-C. Tetrahedron Lett.
1970, 2369. (c) Reutracul, V.; Kanghae, W. Tetrahedron
Lett. 1977, 21377. (d) Durst, T.; Tin, K.-C.; Reinach-
Hirzbach, F.; Decesare, J. M.; Ryan, M. D. Can. J. Chem.
1979, 57, 258; and references cited therein.
H
STol
O
O
4b
6b
Scheme 5
(13) (a) Satoh, T.; Oohara, T.; Ueda, Y.; Yamakawa, K. J. Org.
Chem. 1999, 54, 3130. (b) Satoh, T.; Yamakawa, K. Synlett
1992, 455. (c) Satoh, T.; Hirano, M.; Kuroiwa, A.
Tetrahedron Lett. 2005, 46, 2659.
Acknowledgment
Financial support by the Ministry of Education and Science (Grant
No 3TO9A 18827) is gratefully acknowledged. The author thanks
Prof. M. Mikołajczyk for helpful discussion.
(14) Typical Procedure for Epoxidation.
To a solution of 1 mmol (0.3 g) of (S)-dimethylsulfonium-
(p-tolylsulfinyl)methylide in 5 mL of dry DMSO or 4–5 mL
of MeCN, 0.52 g (1.1 mmol) of NaH was added at r.t. under
an argon atmosphere. The resulting mixture was stirred for
30 min. Then, the precipitate was filtered off and 1 mmol
(0.19 g) of p-bromobenzaldehyde in 1 mL of appropriate
solvent was added. After stirring at r.t. for 2 h, the reaction
was quenched with aq NH4Cl solution (20 mL), extracted
with hexane (4 × 5 mL) and dried over MgSO4. After
filtration, the solvent was evaporated under reduced pressure
affording 4b in 82% of yield as a mixture of trans/cis
isomers in ratio 1.5:1 ratio (DMSO), 2.5:1 (MeCN).
Separation of isomers was achieved by chromatography on
basic alumina (hexane–acetone, 50: 1).
(2S,3S,SS)-3-(p-Bromophenyl)-2-(p-tolylsulfinyl)oxirane
(trans-4b): [a]D22 +52.1 (c 0.6, acetone). 1H NMR (200
MHz, CDCl3): d = 2.42 (3 H, s, CH3PhS), 3.94 (1 H, d,
J = 1.6 Hz, CHPh), 4.54 (1 H, d, J = 1.6 Hz, CHS), 7.11 and
7.45 (4 H, AB system J = 8.4 Hz, Ar), 7.36 and 7.59 (4 H,
AB system J = 8.2 Hz, Ar). 13C NMR (50 MHz): d = 21.5,
29.6, 53.8, 75.7, 123.1, 124.6, 127.5, 130.3, 131.9, 133.0,
137.0, 142.7.
References and Notes
(1) Johnson, A. W.; Lacount, R. B. J. Am. Chem. Soc. 1961, 83,
417.
(2) Corey, E. J.; Chaykovsky, M. J. Am. Chem. Soc. 1965, 87,
1345.
(3) Trost, B. M.; Hammen, R. F. J. Am. Chem. Soc. 1973, 95,
962.
(4) Furukawa, N.; Sugihara, Y.; Fujihara, H. J. Org. Chem.
1989, 54, 4222.
(5) (a) Julienne, K.; Metzner, P.; Henryon, V. J. Chem. Soc.,
Perkin Trans. 1 1999, 731. (b) Davoust, M.; Briere, J.-F.;
Jaffres, P.-A.; Metzner, P. J. Org. Chem. 2005, 70, 4166; and
references cited therein.
(6) (a) Aggarwal, V. K.; Richardson, J. Chem. Commun. 2003,
2644. (b) Aggarwal, V. K.; Alonso, E.; Fang, G.; Ferrara,
M.; Hynd, G.; Porcelloni, M. Angew. Chem. Int. Ed. 2001,
40, 1433. (c) Aggarwal, V. K.; Winn, C. L. Acc. Chem. Res.
2004, 37, 611.
(7) For recent papers, see: (a) Midura, W. H.; Krysiak, J. A.;
Cypryk, M.; Mikołajczyk, M.; Wieczorek, M. W.; Filipczak,
A. D. Eur. J. Org. Chem. 2005, 653. (b) Mikołajczyk, M.;
Midura, W. H.; Michedkina, E.; Filipczak, A. D.;
Wieczorek, M. W. Helv. Chim. Acta 2005, 88, 1769.
(c) Garcia Ruano, J. L.; Fajardo, C.; Martin, M. R.; Midura,
W. H.; Mikołajczyk, M. Tetrahedron: Asymmetry 2004, 15,
2475. (d) Mikołajczyk, M. Pure Appl. Chem. 2005, 77,
2091. (e) Mikołajczyk, M. J. Organomet. Chem. 2005, 2488.
(8) Procedure for Preparation of Sulfonium Salt 2.
To 3 mmol (0.6 g) of (–)-(S)-p-tolylmethylthiomethyl-
sulfoxide excess of MeI (0.5 mL) was added under an argon
(2S,3R,SS)-3-(p-Bromophenyl-2-(p-tolylsulfinyl)oxirane
(cis-4b): [a]D22 –117.1 (c 0.4, acetone). 1H NMR (200 MHz,
CDCl3): d = 2.45 (3 H, s, CH3PhS); 4.08 (1 H, d, J = 3.3 Hz,
CHPh), 4.40 (1 H, d, J = 3.3 Hz, CHS), 7.35 and 7.59 (4 H,
AB system, J = 8.4 Hz, Ar), 7.39 and 7.62 (4 H, AB system,
J = 8.2 Hz, Ar).
(15) (a) de la Pradilla, R. F.; Castro, S.; Manzano, P.; Martin-
Ortega, M.; Priego, J.; Viso, A.; Rodriguez, A.; Fonseca, I.
J. Org. Chem. 1998, 63, 4954. (b) de la Pradilla, R. F.;
Castro, S.; Manzano, P.; Priego, J.; Viso, A. J. Org. Chem.
1996, 61, 3586.
Synlett 2006, No. 5, 733–736 © Thieme Stuttgart · New York

736
W. H. Midura
LETTER
(18) Aggarwal, V. K.; Schade, S.; Taylor, B. J. Chem. Soc.,
(16) The ee was determined by chiral HPLC on Chirobiotic V
column using i-PrOH–hexane (2.5:97.5) as eluent with a
flow rate of 0.4 mL/min. For (R)-5b the second enantiomer
was not detected. Desulfinylation of the crude mixture of 4b
(trans/cis 2.5:1) under the same conditions afforded 5b with
42% ee. The R enantiomer eluted at 187 s and the S
enantiomer at 209 s.
Perkin Trans. 1 1997, 42811.
(19) 1H NMR of the crude sample obtained by rearrangement of
(2S,3S)-4b after 3 d shows the presence of both isomers of
6b in 2:1 ratio.
(20) The mechanistic details of this reaction are under current
investigation.
(17) Pedragosa-Moreau, S.; Morisseau, C.; Zylber, J.; Archelas,
A.; Baratti, J.; Furstoss, R. J. Org. Chem. 1996, 61, 7402.
Synlett 2006, No. 5, 733–736 © Thieme Stuttgart · New York