Nucleophilic epoxidation of γ-alkoxy dienyl sulfoxide derivatives

Article abstract of DOI:10.1016/j.tet.2005.12.024

(E,E) and (Z,E) γ-alkoxy dienyl sulfones undergo nucleophilic epoxidation with remarkable regio- and stereoselectivity to render syn oxiranes in a process mainly controlled by the alkoxy stereocenter. Upon epoxidation γ-hydroxy dienyl sulfoxides provide s

Full text of DOI:10.1016/j.tet.2005.12.024

Tetrahedron 62 (2006) 2684–2692
Nucleophilic epoxidation of g-alkoxy dienyl sulfoxide derivatives
*
´
Roberto Fernandez de la Pradilla, Marıa Victoria Buergo, Carlos Montero and Alma Viso
*
´
´
´
Instituto de Quımica Organica, CSIC, Juan de la Cierva, 3; 28006 Madrid, Spain
Received 21 November 2005; accepted 13 December 2005
Available online 9 January 2006
Abstract—(E,E) and (Z,E) g-alkoxy dienyl sulfones undergo nucleophilic epoxidation with remarkable regio- and stereoselectivity to render
syn oxiranes in a process mainly controlled by the alkoxy stereocenter. Upon epoxidation g-hydroxy dienyl sulfoxides provide sulfinyl
and sulfonyl oxiranes along with bis-epoxides formed through a Payne rearrangement that can be prevented by silylation of the OH
group. Interestingly, the presence of a g-silyloxy group can invert the stereochemical trend of the molecule affording mainly an anti
epoxidation process.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
dienyl sulfones in this epoxidation. Now we report in full
our results (Scheme 1).
The asymmetric epoxidation of electron deficient alkenes
has attracted a great deal of attention in the last decade1 as
an efficient route towards enantiopure functionalized
epoxides, very attractive building blocks.2 In this context,
our group has demonstrated that simple a,b-unsaturated
sulfoxides A (R1ZH) undergo nucleophilic epoxidation by
treatment with metalated hydroperoxides with complete
preservation of double bond geometry and with moderate
to excellent facial selectivity to produce enantio- and
diastereomerically pure a,b-epoxy sulfoxides B (R1ZH).
Related 2-sulfinyl dienes A (R1Zvinyl) have also resulted
suitable substrates for these epoxidations and the facial
diastereoselectivity may be controlled by the choice of the
counterion (LiOO-t-Bu vs NaOO-t-Bu).3 Subsequently, we
have explored the behavior of a0-(1-hydroxyalkyl)vinyl
sulfoxides C,4 and g-alkoxy vinyl sulfoxides D (R1ZH,
PZTBS, BPS),5 bearing an additional stereocenter and with
a reinforcing/non-reinforcing scenario being operative. The
above work has led to the development of a new method for
the synthesis of enantiopure sulfinyl and sulfonyl oxiranes
B, E and F.6 In connection with these efforts, we have also
examined the nucleophilic epoxidation of g-hydroxy dienyl
sulfoxides D (R1Zvinyl). Among others, we have studied
the effect of the E/Z geometry on the electrophilic double
bond, of the relative configuration of the hydroxyl and
sulfinyl stereocenters, of the protection at the hydroxyl
group as well as the reactivity of the related g-hydroxy
p-Tol
p-Tol
O
S
S
O
O
R
R
MOO-t-Bu
R1
A
R1
B
R1 = H, vinyl
p-Tol
p-Tol
O
S
S
(
)
n
O
O
R
MOO-t-Bu
R
OH
R2
E
R2
OH
n = 1, 2
p-Tol
C
p-Tol
R3
O
MOO-t-Bu R3
1 = H, vinyl
S
S
O
(
)
n
O
R1
R1
OP
OP
R
D
F n = 1, 2
P = H, TBS, BPS
Scheme 1.
2. Discussion and results
2.1. Preparation of the starting dienes
The set of dienyl sulfoxides and sulfones chosen for this
study was synthesized following a procedure previously
reported by us.7 The method entails submitting the two
diastereomeric anti sulfinyl chlorohydrins G to one-pot
base-induced (KO-t-Bu) epoxide formation/rearrangement
to generate enantiopure hydroxy 2-sulfinyl dienes D through
the diasteromeric epoxy vinyl sulfoxides H that, if desired,
can also be isolated. This efficient reaction allows for the
selective synthesis of E/E or Z/E dienyl sulfoxides D
depending on the relative stereochemistry of the sulfinyl
Keywords: Sulfoxides; Sulfones; Dienes; Nucleophilic epoxidation.
*
Corresponding authors. Fax: 34 91 564 4853;
e-mail addresses: iqofp19@iqog.csic.es; iqov379@iqog.csic.es
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.12.024

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R. Fernandez de la Pradilla et al. / Tetrahedron 62 (2006) 2684–2692
2685
chlorohydrin precursor, G. Further oxidation (MMPP)
allowed for the simple transformation of dienyl sulfoxides
D into g-hydroxy dienyl sulfones I without any detectable
loss of stereochemical integrity. In particular, dienyl
sulfoxides 1 and 3, and dienyl sulfones 6 and 7 were
prepared for the present work. In addition, (E,E)-g-hydroxy
dienyl sulfoxide 1 was submitted to Mitsunobu conditions
followed by debenzoylation to give diastereomeric diene 2
in good yield and as a single isomer. Finally, to assess the
influence of the hydroxyl group in the epoxidation process
dienyl sulfoxide 1 as well as dienyl sulfone 6 were protected
as silyl ethers in good yields to afford dienes 4 and 8,
respectively. Surprisingly, (Z,E)-dienyl sulfoxide 3 showed a
low reactivity under silylation conditions and the resulting
silyloxy diene 5 was unstable under standard chromato-
graphic purification leading to E/E dienes and diastereomeri-
zation at sulfur.8 However, with careful manipulation a small
amount of 5 could be isolated and then treated with MMPP to
afford g-silyloxy dienyl sulfone 9 in good yield (Scheme 2).
R3
HO
Cl
R3
O
O
S
O
S
p-Tol
Base
p-Tol
OH
R4
G
R4
H
R3
R3
OH
O
S
SO2p-Tol
p-Tol
[O]
R4
R4
D
I
OP
n-Bu
p-Tol
p-Tol
p-Tol
S
( )
O
n
S
S
n-Bu
n-Bu
(a)
( )
O
O
n
PO
n-Pr
1, P = H, n = 1
HO
n-Pr
n-Pr
(b) or (c)
2
3, P = H, n = 1
7, P = H, n = 2
(b)
(c)
(d)
(d)
4, P =TBDMS, n = 1
6, P = H, n = 2
5, P = TBDMS, n = 1
9, P = TBDMS, n = 2
8, P = TBDMS, n = 2
2.2. Nucleophilic epoxidation of dienyl sulfoxides
and sulfones
(a) i. PPh3, DIAD, p-NO2C6H4CO2H, 0 oC THF, 90 min; ii.
K2CO3, MeOH, 0 oC, 2 h, 72% overall yield. (b) TBDMSCl,
imidazole, CH2Cl2, 0 oC to rt, 95 min, 79%. (c) TBDMSOTf,
Et3N, DMAP, 0 oC to rt, 23 min, 98%. (d) MMPP, MeOH, rt, 24 h,
60–64%.
At the beginning of this study, we submitted (E,E)-dienyl
sulfones 6 and 8 to epoxidation with NaOO-t-Bu to assess
the effect of the alkoxy group as the only stereocenter in the
molecule (Table 1, entries 1 and 2). The nucleophilic
epoxidation of g-hydroxy dienyl sulfone 6 was remarkably
Scheme 2.
Table 1. Nucleophilic epoxidation of g-alkoxy dienyl sulfoxides and sulfones
p-Tol
p-Tol
p-Tol
O
O
n-Bu
+
O
O
S
SO2p-Tol
S
n-Bu
HO
n-Pr
n-Bu
n-Bu
HO
n-Pr
S
n-Bu
(
O
)
O
O
n-Bu
O
O
n
+
+
HO
n-Pr
+
ent-10 ent-11a,b
+
ent-11c
HO
n-Pr
O
O
single isomer
(44:56)
n-Pr
11c
n-Pr
11a,b
(44:56)
1, n = 1
6, n = 2
10
2
15
single isomer
p-Tol
p-Tol
OH
OH
p-Tol
p-Tol
n-Bu
n-Bu
O
O
S
n-Bu
TBDMSO
n-Pr
SO2p-Tol
+
S
n-Bu
n-Bu
S
S
(O)
n
(
)
n
O
(
)
n
(
)
n
O
O
+
O
TBDMSO
n-Pr
12
TBDMSO
n-Pr
ent-11c
single isomer
ent-11a,b
(50:50)
+
n-Pr
n-Pr
4, n = 1
8, n = 2
13, n = 1
14, n = 2
3, n = 1
7, n = 2
16, n = 1
17, n = 2
Entry
Compounds
Conditionsa
syn
16
anti
Yield
(%)b
10/ent-10
12
15
17
11a,b/
ent-11a,bc
13
14
11c/ent-11cd
1
2
6
8
NaOOt-Bu,
105 m
NaOOt-Bu,
4 days
NaOOt-Bu, 3 h
KOOt-Bu, 4 days
NaOOt-Bu, 70 m
NaOOt-Bu, 55 m
NaOOt-Bu, 45 m
100 (10)
89
46
10
54
47
75e
3
4
5
6
7
1
4
2
7
3
27 (10)
52 (11a,b)
21 (11c)
62
43
82f
93
4 (ent-10)
80
11 (ent-11a,b)
2 (ent-11a,b)
5 (ent-11c)
22 (ent-11c)
100
4
82
61g
72
a All reactions were conducted in THF at 0 8C.
b Combined yield of isolated epoxides.
c As a 44:56 mixture of diastereomers except for entry 7 where an equimolecular mixture was detected.
d As a single isomer. The absolute configuration was not confirmed.
e Starting material (5%) in the crude reaction mixture (1H NMR).
Starting material (12%) in the crude reaction mixture (1H NMR).
f
g Starting material (11%) in the crude reaction mixture (1H NMR).

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R. Fernandez de la Pradilla et al. / Tetrahedron 62 (2006) 2684–2692
2686
regio- and stereoselective affording syn sulfonyl oxirane 10
as a single diastereoisomer. In contrast, g-silyloxy dienyl
sulfone 8 underwent a slower epoxidation (O4 days) to give
a 46:54 mixture of syn and anti sulfonyl oxiranes 12 and 14
under similar reaction conditions. To further probe the
stereochemical assignment of the above sulfonyl oxiranes,
10 was silylated using TBDMSCl and imidazole rendering
12 with a moderate yield (29%) and conversion (70%
recovered starting material), however, at this point we did
not further optimize this reaction. The high stereodirecting
capability of the free hydroxyl group was again observed for
the nucleophilic epoxidation of (Z,E)-g-hydroxy dienyl
sulfone 7 (entry 6). Thus treatment of 7 with NaOO-t-Bu in
THF afforded exclusively syn sulfonyl oxirane 17 in 55 min
and with an excellent yield (82%).
require rotation around Cb–Cg to adopt a suitable
arrangement and this slows down the Payne rearrangement.
The behavior of dienyl sulfoxide 2 with opposite relative
configuration at the stereocenters is parallel to 1. Thus,
nucleophilic epoxidation of 2 afforded after 70 min an
80:4:11:5 mixture of syn sulfinyl oxirane 15, syn sulfonyl
oxirane ent-10 and bis-epoxides 11ab (44:46) and 11c.
Stereochemical correlation between 15 and ent-10 was
easily provided by oxidation of 15 with MMPP to render
ent-10 in 59% yield. Taking into account the overall ratio of
final epoxides, hydroxy dienyl sulfoxide 2 provides a 95:5
mixture of syn and anti epoxides10 with a reinforcing
combination of stereodirecting elements (hydroxyl and
sulfinyl) while 1 provides a 79:21 syn:anti mixture with a
non-reinforcing arrangement of the stereocenters.
Subsequently we examined the behavior of (E,E)-g-
hydroxy dienyl sulfoxides 1 and 2 with an additional
stereocenter at sulfur (entries 3 and 5). Treatment of 1 with
NaOO-t-Bu after 3 h provided as minor product sulfonyl
oxirane 10 (27%) along with bis-epoxides 11ab (52%, as a
44:55 mixture of diastereoisomers) and 11c (21%, as a
single diastereoisomer). Shortening the reaction time
allowed for detection of variable amounts of the sulfinyl
oxirane (100 not shown) precursor of 10, however, starting
material was always recovered. The formation of bis-
epoxides 11a–c has been rationalized in terms of a Payne
rearrangement,9 (Scheme 3) of sulfinyl oxiranes J (anti) and
K (syn) to generate a,b-unsaturated epoxy ketones L and M
that undergo in situ second selective or non selective
nucleophilic epoxidation providing 11c and 11ab, respec-
tively. In this context, minor anti oxirane J would suffer a
rapid Payne process while major syn oxirane K would
As expected, protection of the hydroxyl group as silyl ether
prevented the Payne rearrangement from taking place,
however, a lower reactivity as well as a reversal of
stereoselectivity was observed (entry 4). In fact, epoxidation
of g-silyloxy dienyl sulfoxide 4 was carried out with the
more reactive KOO-t-Bu3–5 affording a mixture of sulfonyl
oxiranes 12 (10) and 14 (47) along with sulfinyl oxirane 13
(43). A chemical correlation between 13 and 14 was
established by treatment of 13 with MMPP to give 14 in
74% yield. The inversion of the overall syn:anti ratio
(10:90) compared with 1 (syn:anti, 79:29) is noteworthy.11
Finally, to assess the influence of the stereochemistry of the
double bond, the nucleophilic epoxidation of (Z,E)-g-
hydroxy dienyl sulfoxide 3 was examined (Table 1, entry
7). The reaction mixture showed a mixture of syn sulfinyl
and sulfonyl oxiranes 16 (72) and 17 (4) and again
significant amounts of bis-epoxides ent-11a,b (2) and ent-
11c (22) from the Payne rearrangement with an overall
syn:anti ratio of 78:22. Further oxidation (MMPP) of 16
rendered 17 in 62% yield. At this point, we envisioned the
protection of the free hydroxyl group to prevent the Payne
process. However, the silylation of 3 was not a straightfor-
ward process due to the unstable nature of 5 and,
surprisingly, g-silyloxy dienyl sulfone 9 was unreactive
under the nucleophilic epoxidation conditions examined.
Therefore, we did not pursue any further the epoxidation of
these (Z,E)-dienes.
p-Tol
p-Tol
O
O
S
S
n-Bu
n-Bu
n-Bu
O
O
O
NaO
n-Pr
HO
n-Pr
Payne
fast
anti
n-Pr
J
L
1
syn
selective
p-Tol
epoxidation
O
O
O
S
n-Bu
NaO
The structural assignment of the epoxides was based mainly
in their NMR data. The oxidation state at sulfur was
determined by the slightly higher chemical shifts of H-ortho
(p-TolS), H (epox) and C (arom)-S for sulfonyl oxiranes.
The relative configuration of the sulfinyl and sulfonyl
oxiranes was indirectly assessed through the cis/trans
stereochemistry of bis epoxides (see Scheme 3): 11a,b
[J1,3(cis-butyl oxirane)Z4.8 Hz, syn epoxidation] and 11c
[J1,3(trans-butyl oxirane)Z1.9 Hz, anti epoxidation].
O
n-Bu
n-Bu
O
O
Payne
slow
O
n-Pr
n-Pr
n-Pr
11c
M
K
non selective
epoxidation
O
The stereochemical outcome of the nucleophilic epoxida-
tion is primarily controlled by stereoelectronic effects and
can be understood in terms of an initial nucleophilic attack
of the metalated peroxide to the reactive conformers of the
alkoxy dienes (Scheme 4). For (E,E)-dienyl sulfoxides 1 and
2, an s-cis conformation for the unsaturated sulfoxide (CaZ
Cb/S-:),12 along with an s-trans conformation for the dienyl
O
n-Bu
O
n-Pr
11a,b
Scheme 3.

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R. Fernandez de la Pradilla et al. / Tetrahedron 62 (2006) 2684–2692
2687
sulfoxides provide sulfinyl and sulfonyl oxiranes, along
with significant amounts of bis-epoxides probably formed
through a Payne rearrangement that can be prevented by
silylation of the OH group. In terms of stereochemistry,
an additional stereocenter at sulfur implies a reinforcing/
non-reinforcing scenario with the free hydroxyl group as the
stronger syn stereodirecting element of the epoxidation.
Interestingly, the presence of a g-silyloxy group can invert
the stereochemical outcome of the process affording mainly
an anti epoxidation process.
OH and sulfinyl control
OH
n-Pr
H
syn:anti, 95:5
H
O
.
S
.
p-Tol
n-Bu
reinforcing
(E,E)-2
sulfinyl control
H
n-Pr
n-Bu
H
OH control
O
.
S
.
syn:anti, 79:21
p-Tol
OH
non reinforcing
3. Experimental
P = H, (E,E)-1
3.1. General procedures
sulfinyl and silyl ether control
Reagents and solvents were handled by using standard
syringe techniques. Hexane, toluene, and CH2Cl2 were
distilled from CaH2, and Et2O from sodium. DMF was dried
over CaH2 and filtered before distillation under reduced
n-Pr
n-Bu
H
H
syn:anti, 10:90
O
.
S
.
˚
p-Tol
OTBDMS
reinforcing
pressure. Then, it was collected over 4 A molecular sieves
and argon was bubbled through for 10 min before storing it.
Et3N was distilled from CaH2. Crude products were purified
by flash chromatography on Merck 230–400 mesh silica gel
with distilled solvents. Analytical TLC was carried out on
Merck (Kieselgel 60F-254) silica gel plates with detection
by UV light, iodine, acidic vanillin solution, 10%
phosphomolybdic acid solution in ethanol. All reagents
were commercial products purchased from Aldrich, Acros,
Fluka or Merck. Organolithium reagents were titrated by
reaction with 3,4-dimethoxybenzaldehyde prior to use. NaH
and KH (60% in mineral oil) were washed repeatedly with
dry hexane and dried prior to use. Through this section, the
volume of solvents is reported in mL/mmol of starting
material. Infrared spectra (IR) were obtained on a Perkin-
(E,E)-4
sulfinyl control
.
.
O
n-Bu
S
H
H
p-Tol
syn:anti, 78:22
OH control
HO
n-Pr
(Z,E)-3 non reinforcing
Scheme 4.
system would be probably adopted to minimize A1,3 strain
stronger than A1,2 strain caused by the interaction between
the sulfinyl and butenyl groups. Besides, in agreement with
the observed coupling constant between allylic and vinylic
protons for the dienes (JZ8–9 Hz) the Cg–H bond would be
coplanar to the dienyl system with a dihedral angle of
1808.13 In this context, the diastereofacial selectivity for
each substrate (1 and 2) would be determined by the relative
configuration of the two stereogenic centers, sulfoxide and
hydroxyl group. A reinforcing scenario is working for 2 that
produces a 95:5 mixture of epoxidation syn to the OH group,
while a non reinforcing contribution of the sulfoxide
diminishes the stronger stereodirecting ability of the
hydroxyl group in 1 to provide a less selective epoxidation
(syn:anti, 79:21). However, for this particular relative
stereochemistry, the presence of a silyl ether (4) results in
a reinforcing scenario and thus reverts the syn:anti outcome
of the epoxidation (10:90).11 Similarly, (Z,E)-dienyl
sulfoxide 3 would adopt an s-cis reactive conformation for
the dienyl system and the nucleophilic epoxidation would
occur mainly syn (syn:anti, 78:22) to the hydroxyl group
since a non reinforcing contribution of the stereodirecting
elements is taking place.
Elmer 681 and on a Perkin-Elmer Spectrum one. 1H and 13
C
NMR spectra were recorded on a Bru¨ker AM-200
(200 MHz), Varian Gemini-200 (200 MHz), Varian
INOVA-300 (300 MHz) and Varian INOVA-400
(400 MHz) using CDCl3 as solvent and with the residual
solvent signal as internal reference (CDCl3, 7.24 and
77.0 ppm). The following abbreviations are used to describe
peak patterns when appropriate: s (singlet), d (doublet), t
(triplet), q (quartet), m (multiplet), br (broad). Melting
points were determined on a Reichert Kofler microscope
and are uncorrected. Optical rotations were measured on a
Perkin-Elmer 241 polarimeter at 20 8C using a sodium lamp
and in CHCl3 solution. Low resolution mass spectra were
recorded by direct injection on a Hewlett Packard 5973
MSD instrument using the electronic impact technique with
an ionization energy of 70 eV or on a Hewlett Packard 1100
MSD instrument using the atmospheric pressure chemical
ionization (APCI) or electrospray (ES) chemical ionization
techniques in its positive or negative modes. Elemental
analyses were carried out on a Perkin-Elmer 240 C and on a
´
Heraus CHN-O-Rapid instruments at Instituto de Quımica
´
Organica, CSIC (Madrid).
In summary, we have demonstrated that (E,E) and (Z,E)
g-hydroxy dienyl sulfones undergo nucleophilic epoxida-
tion with remarkable regio- and stereoselectivity to
render syn epoxides in a process mainly controlled by the
hydroxyl stereocenter. Upon epoxidation, g-hydroxy dienyl
3.2. General procedure for silylation of sulfinyl alcohols
(a) With tert-butyldimethylsilyl chloride: under an atmo-
sphere of argon, 1.1 equiv of tert-butyldimethylsilyl
chloride was added to a cold (0 8C) solution of the sulfinyl

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2688
alcohol and 1.2 equiv of imidazole in CH2Cl2 (10 mL/
mmol) and the reaction mixture was allowed to warm up to
rt and monitored by TLC. Upon completion the reaction was
quenched with H2O (1 mL/mmol), diluted with CH2Cl2
(10 mL/mmol) and the layers were separated. The aqueous
phase was extracted with CH2Cl2 (three times, 10 mL/
mmol) and the combined organic extracts were washed with
a saturated solution of NaCl (4 mL/mmol), dried over
MgSO4, filtered and concentrated under reduced pressure to
give a crude product that was purified by column
chromatography on silica gel using a gradient of the
appropriate solvents. (b) With tert-butyldimethylsilyl
triflate: under an atmosphere of argon, 2.0 equiv of freshly
distilled tert-butyldimethylsilyl triflate was added to a cold
(0 8C) solution of the sulfinyl alcohol, 2 equiv of Et3N and
2–3 crystals of DMAP in THF (7 mL/mmol) and the
reaction mixture was allowed to warm up to rt and
monitored by TLC. Upon completion 3 equiv of Et3N was
added and the reaction was quenched with a saturated
solution of NaHCO3 (4 mL/mmol) and H2O (4 mL/mmol),
diluted with EtOAc (10 mL/mmol) and the layers were
separated. The aqueous phase was extracted with EtOAc
(three times, 10 mL/mmol) and the combined organic
extracts were washed with a saturated solution of NaCl
(4 mL/mmol), dried over MgSO4, filtered and concentrated
under reduced pressure to give a crude product that was
purified by column chromatography on silica gel using a
gradient of the appropriate solvents.
EtOAc–hexane), 11.6 mg (34%) of an inseparable mixture
(20:80) of silylated dienes 50 and ent-4 was obtained as a
colorless oil. (b) From hydroxy dienyl sulfoxide 3 (14.3 mg,
0.044 mmol) in DMF (1.0 mL), Et3N (9 mg, 12 mL,
0.089 mmol), 2 crystals of DMAP, tert-butyldimethylsilyl
triflate (18.1 mg, 16 mL, 0.067 mmol) according to the
general procedure (3 h, two additions of reagents in the
above amounts), after chromatography (5–30% EtOAc–
hexane), 5.9 mg (32%) of diene 5 was obtained as a
colorless oil, rather unstable in silica gel, and 7.4 mg (52%)
of starting material was obtained. (c) From hydroxy dienyl
sulfoxide 3 (24.5 mg, 0.07 mmol) in THF (0.53 mL), Et3N
(15.2 mg, 21 mL, 0.15 mmol), 2 crystals of DMAP, tert-
butyldimethylsilyl triflate (26 mL, 29.9 mg, 0.11 mmol)
according to the general procedure (6 h 20 min, four
additions of reagents in the above amounts), after
chromatography (5–30% EtOAc–hexane), 15 mg (49%) of
a 32:68 inseparable mixture of 50 and ent-4 was obtained.
Data for 5: RfZ0.42 (20% EtOAc–hexane). [a]2D0 K82.0 (c
0.68). 1H NMR (300 MHz) d 0.03 (s, 3H, TBDMS), 0.07 (s,
3H, TBDMS), 0.73 (t, 3H, JZ7.4 Hz), 0.88 (t, 3H, JZ
5.9 Hz), 0.89 (s, 9H, TBDMS), 1.19–1.70 (m, 8H), 1.94 (q,
2H, JZ6.7 Hz), 2.37 (s, 3H, CH3–p-Tol), 5.07 (q, 1H, JZ
6.7 Hz, H-5), 5.74 (d, 1H, JZ15.7 Hz, H-8), 5.95 (dt, 1H,
JZ15.7, 6.6 Hz, H-9), 6.08 (d, 1H, JZ8.7 Hz, H-6), 7.25 (d,
2H, JZ8.5 Hz, ArH), 7.44 (d, 2H, JZ8.2 Hz, ArH). 13C
NMR (50 MHz) d K4.2, K4.1, 13.4, 14.0, 19.1, 21.3, 22.6,
25.8 (3C), 27.1, 29.7, 35.0, 38.4, 69.0, 121.1, 124.7 (2C),
129.6 (2C), 136.9, 139.5, 140.5, 140.6, 141.4. IR (CCl4):
2930, 2900, 2820, 1720, 1480, 1450, 1240, 1060, 1030,
1000, 780 cmK1. MS (APCI): 425 [MCNa]K, 171 (100%).
Data for 50 from a 38:68 mixture of 50 and ent-4: RfZ0.40
3.2.1. Synthesis of tert-butyldimethylsilyl ether of (D)-
(5R,SS)-(6E,8E)-7-(p-tolylsulfinyl)-6,8-dodecadien-5-ol,
4. From hydroxy dienyl sulfoxide 1 (15.8 mg, 0.049 mmol)
in CH2Cl2 (0.50 mL), imidazole (4 mg, 0.06 mmol), tert-
butyldimethylsilyl chloride (8.4 mg, 0.05 mmol) according
to the general procedure (95 min), after chromatography
(5–50% Et2O–hexane), 16.8 mg (79%) of silylated diene 4
was obtained as a colorless oil. Data for 4: RfZ0.37 (30%
EtOAc–hexane). [a]D20 C81.1 (c 0.90). 1H NMR (300 MHz)
d K0.05 (s, 3H, TBDMS), K0.02 (s, 3H, TBDMS), 0.77 (t,
3H, JZ7.4 Hz), 0.83–0.85 (m, 3H), 0.84 (s, 9H, TBDMS),
1.21–1.36 (m, 6H), 1.45–1.62 (m, 2H), 1.99 (m, 2H), 2.35
(s, 3H, CH3–p-Tol), 4.46 (ddd, 1H, JZ8.7, 7.2, 5.5 Hz, H-
5), 5.83 (m, 2H, H-8, H-9), 6.32 (d, 1H, JZ8.7 Hz, H-6),
7.21 (dd, 2H, JZ8.5, 0.6 Hz, ArH), 7.45 (d, 2H, JZ8.3 Hz,
ArH). 13C NMR (50 MHz) d K4.8, K4.3, 13.4, 14.0, 18.1,
21.4, 22.1, 22.6, 25.8 (3C), 27.3, 35.5, 37.7, 69.2, 119.5,
125.5 (2C), 129.6 (2C), 135.5, 138.6, 140.6, 141.4. IR
(CCl4): 2920, 2900, 2820, 1620, 1570, 1480, 1440, 1240,
1060, 1030, 990, 820, 790 cmK1. Anal. Calcd for
C25H42O2SSi: C, 69.07; H, 9.74; S, 7.38. Found: C, 69.13;
H, 9.55; S, 7.23.
1
(20% EtOAc–hexane). H NMR (200 MHz) d K0.06 (s,
3H, TBDMS), K0.03 (s, 3H, TBDMS), 0.75–0.92 (m, 6H, 2
CH3), 0.82 (s, 9H, TBDMS), 1.16–1.36 (m, 6H), 1.40–1.61
(m, 2H), 1.98 (m, 2H), 2.36 (s, 3H, CH3–p-Tol), 4.48 (m,
1H, H-5), 5.84 (m, 2H, H-8 and H-9), 6.31 (d, 1H, JZ
8.4 Hz, H-6), 7.21 (d, 2H, JZ8.1 Hz, ArH), 7.47 (d, 2H, JZ
8.2 Hz, ArH). The data of ent-4 was identical to its
enantiomer.
3.2.3. Synthesis of tert-butyldimethylsilyl ether of (D)-
(5R)-(6E,8E)-7-(p-tolylsulfonyl)-6,8-dodecadien-5-ol, 8.
From hydroxy dienyl sulfone 6 (29.3 mg, 0.087 mmol) in
THF (0.61 mL), Et3N (26.3 mg, 36 mL), 2 crystals of
DMAP, tert-butyldimethylsilyl triflate (34.5 mg, 30 mL,
0.130 mmol) according to the general procedure (23 min),
after chromatography (5–50% EtOAc–hexane), 35.6 mg
(98%) of 8 was obtained as a pale yellow oil. Data for 8:
1
RfZ0.43 (20% EtOAc–hexane). [a]2D0 C24.1 (c 0.85). H
NMR (300 MHz) d K0.07 (s, 3H, TBDMS), K0.04 (s, 3H,
TBDMS), 0.80 (t, 3H, JZ7.3 Hz), 0.84 (s, 9H, TBDMS),
0.86 (t, 3H, JZ7.0 Hz), 1.22–1.44 (m, 6H), 1.54–1.61 (m,
2H), 2.02 (q, 2H, JZ6.9 Hz), 2.40 (s, 3H, CH3–p-Tol), 4.38
(m, 1H, H-5), 5.81 (d, 1H, JZ16.1 Hz, H-8), 5.87 (dt, JZ
15.9, 6.1 Hz, H-9), 6.74 (d, 1H, JZ8.6 Hz, H-6), 7.26 (d,
2H, JZ7.9 Hz, ArH), 7.66 (d, 2H, JZ8.2 Hz, ArH). 13C
NMR (75 MHz) d K4.9, K4.3, 13.5, 14.0, 18.1, 21.6, 22.0,
22.5, 25.7 (3C), 27.2, 35.4, 37.1, 69.0, 118.2, 128.2 (2C),
129.5 (2C), 136.8, 138.5, 141.2, 143.0, 144.0. IR (CCl4):
2910, 2820, 1630, 1580, 1470, 1440, 1390, 1300, 1240,
1150, 1070, 920, 650 cmK1. Anal. Calcd for C25H42O3SSi:
C, 66.62; H, 9.39; S, 7.11. Found: C, 66.74; H, 9.59; S, 7.03.
3.2.2. Synthesis of tert-butyldimethylsilyl ether of (L)-
(5S,SS)-(6Z,8E)-7-(p-tolylsulfinyl)-6,8-dodecadien-5-ol,
5, tert-butyldimethylsilyl ether of (5S,SS)-(6E,8E)-7-(p-
tolylsulfinyl)-6,8-dodecadien-5-ol, 50, and tert-butyldi-
methylsilyl ether of (5S,RS)-(6E,8E)-7-(p-tolylsulfinyl)-
6,8-dodecadien-5-ol, ent-4. Three different procedures (a),
(b), and (c) were employed for the synthesis of 5. (a) From
hydroxy dienyl sulfoxide 3 (25.5 mg, 0.08 mmol) in CH2Cl2
(1.0 mL), imidazole (6.5 mg, 0.10 mmol), tert-butyldi-
methylsilyl chloride (13.6 mg, 0.09 mmol) according to
the general procedure (27 h), after chromatography (5–50%

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2689
3.3. General procedure for oxidation of sulfoxides
with MMPP
dienyl sulfone 6 (26.2 mg, 0.078 mmol) in THF (0.50 mL),
according to the general procedure (0 8C, 105 min), hydroxy
sulfonyl oxirane 10 was obtained. Purification by chroma-
tography (5–30% EtOAc–hexane) gave 24.5 mg (89%) of
10 as a colorless oil. Data for 10: RfZ0.34 (30% EtOAc–
hexane). [a]2D0 K43.5 (c 1.01). 1H NMR (300 MHz) d 0.75
(t, 3H, JZ7.3 Hz), 0.88 (t, 3H, JZ7.3 Hz), 1.20–1.32 (m,
6H), 1.46–1.70 (m, 2H), 1.92 (br s, 1H, OH), 1.96 (ap q, 2H,
JZ6.6 Hz), 2.42 (s, 3H, CH3–p-Tol), 3.28 (dt, 1H, JZ8.0,
5.6 Hz, H-10), 3.81 (d, 1H, JZ8.2 Hz, H-3), 5.65 (dt, 1H,
JZ15.6, 6.7 Hz, H-200), 5.79 (dt, 1H, JZ15.5, 1.2 Hz,
H-100), 7.30 (dd, 2H, JZ8.5, 0.6 Hz, ArH), 7.68 (dd, 2H,
JZ8.4, 1.9 Hz, ArH). 13C NMR (75 MHz) d 13.4, 13.8, 21.7
(2C), 22.5, 26.8, 33.0, 34.2, 65.1, 69.6, 76.0, 116.3, 129.4
(2C), 129.6 (2C), 132.4, 141.3, 145.3. IR (CCl4): 3460,
To a cold (0 8C) solution of sulfoxide in MeOH (10 mL/
mmol) was added 1.5 equiv of magnesium monoperoxy-
phthalate hexahydrate (MMPP). The mixture was stirred from
0 8C to rt, monitored by TLC until completion and then
quenched with a saturated solution of NaHCO3 (4 mL/mmol).
After removal of MeOH under reduced pressure, the mixture
was diluted with EtOAc (5 mL/mmol), the layers were
separated and the aqueous phase was extracted with EtOAc
(three times, 4 mL/mmol). The combined organic layers were
washed with a saturated solution of NaCl (1 mL/mmol), dried
over MgSO4, filtered and concentrated under reduced
pressure to give a crude product that was purified by gradient
column chromatography using EtOAc–hexane mixtures.
2920, 2900, 2840, 1640, 1580, 1450, 1240, 1170, 640 cmK1
.
MS (APCI): 353 [MC1]C, 197 (100%). Anal. Calcd for
C19H28O4S: C, 64.74; H, 8.01; S, 9.10. Found: C, 64.55; H,
8.22; S, 9.09.
3.3.1. Synthesis of tert-butyldimethylsilyl ether of (D)-
(5S)-(6Z,8E)-7-(p-tolylsulfonyl)-6,8-dodecadien-5-ol, 9.
From sulfinyl diene 5 (10.5 mg, 0.026 mmol) in MeOH
(0.30 mL) and MMPP (64.3 mg, 0.104 mmol), according to
the general procedure (24 h), after chromatography (2–15%
EtOAc–hexane), dienyl sulfone 9 (7 mg, 64%) was obtained
as a colorless oil. Data for 9: RfZ0.30 (2!15% EtOAc–
3.4.2. Synthesis of (2S,3S,10R)-(E)-3-[10-(tert-butyldi-
methylsilyloxy)-n-pentyl]-2-(1-pentenyl)-2-(p-tolylsul-
fonyl)oxirane, 12, and (2R,3R,10R)-(E)-3-[10-(tert-
butyldimethylsilyloxy)-n-pentyl]-2-(1-pentenyl)-2-
(p-tolylsulfonyl)oxirane, 14. From NaH (6.4 mg,
0.26 mmol) in THF (1.30 mL), t-BuOOH (33 mL, 30 mg,
0.26 mmol) and a solution of dienyl sulfone 8 (27.8 mg,
0.066 mmol) in THF (0.46 mL), according to the general
procedure (4 days, 6 h), a 44:51:5 mixture of sulfonyl
oxiranes 12 and 14 and starting material was obtained.
Purification by chromatography (5–30% EtOAc–hexane)
gave 22.3 mg (75%) of an inseparable mixture of 12 and 14
as a colorless oil, and 2 mg (5%) of starting material.
Spectral data measured for 12 and 14 was identical to those
described below.
1
exane). H NMR (300 MHz) d K0.06 (s, 3H, TBDMS),
0.04 (s, 3H, TBDMS), 0.81 (t, 3H, JZ7.3 Hz), 0.85 (s, 9H,
TBDMS), 0.88 (t, 3H, JZ5.9 Hz), 1.24–1.38 (m, 8H,
4CH2), 2.01 (qd, 2H, JZ7.3, 1.5 Hz, H-4), 2.40 (s, 3H,
CH3–p-Tol), 5.31 (dt, 1H, JZ7.9, 3.8 Hz, H-5), 5.77 (dt,
1H, JZ15.5, 7.0 Hz, H-9), 6.06 (d, 1H, JZ8.1 Hz, H-6),
6.05 (d, 1H, JZ15.0 Hz, H-8), 7.28 (d, 2H, JZ8.5 Hz,
ArH), 7.70 (d, 2H, JZ8.3 Hz, ArH). 13C NMR (50 MHz) d
K4.8, K4.4, 13.5, 14.0, 18.1, 21.6, 22.0, 22.6, 25.8 (3C),
27.4, 34.8, 37.7, 68.3, 124.3, 127.7 (2C), 129.5 (2C), 134.0,
137.0, 137.6, 144.2, 144.7.
3.4.3. Synthesis of (L)-(2S,3S,10R,SS)-(E)-3-(10-hydroxy-
pentyl)-2-(pentenyl)-2-(p-tolylsulfinyl)oxirane, 100, (L)-
(2S,3S,10R)-(E)-3-(10-hydroxypentyl)-2-(1-pentenyl)-2-
(p-tolylsulfonyl)oxirane, 10, (7R,8R)-6-oxadodecanyl-4,7-
bis-oxirane, 11c, (7S,8R)-6-oxadodecanyl-4,7-bis-oxirane,
11a,b. From NaH (7.8 mg, 0.32 mmol) in THF (1.60 mL),
t-BuOOH (41 mL, 37 mg, 0.32 mmol) and a solution of
dienyl sulfoxide 1 (26 mg, 0.081 mmol) in THF (0.56 mL),
according to the general procedure (1 h), a 46:9:18:9:18
mixture of 100, 11c, 11a,b, 10 and 1 was obtained (1H NMR
of an aliquot). After 2 h (total reaction time), a
26:10:38:16:10 mixture of 100, 11c, 11a,b, 10 and 1 was
obtained. Purification by chromatography (5–50% EtOAc–
hexane) gave 4.25 mg (25%) of bis oxiranes 11c and 11a,b,
3.25 mg (11%) of sulfonyl oxirane 10, 4.15 mg (21%) of
sulfinyl oxirane 100 and 3.7 mg (7%) of starting material as
colorless oils. Alternatively, from NaH (13.5 mg,
0.40 mmol) in THF (2.15 mL), t-BuOOH (55 mL, 50 mg,
0.40 mmol) and a solution of dienyl sulfoxide 1 (35.2 mg,
0.11 mmol) in THF (0.76 mL), according to the general
procedure (3 h) a 21:52:27 mixture of bis oxiranes 11c and
11a,b and sulfonyl oxirane 10 was obtained. Purification by
chromatography (5–50% Et2O–hexane) gave 4 mg (18%)
of 11c and 10 mg (44%) of 11a,b. Data for 100: RfZ0.21
3.4. General procedure for nucleophilic epoxidation
of dienyl sulfoxides and sulfones
A two-necked round-bottomed flask fitted with a tube in T
for entrance and exit of argon and a polyethylene stopper,
was charged with anhydrous THF (5 mL/mmol) and
2–4 equiv of oil free NaH or KH (washed with hexane
and dried), the mixture was cooled to 0 8C and then
2–4 equiv of t-BuOOH (80% in t-BuOO-t-Bu) was added.
After stirring at rt for 20–30 min, the resulting solution was
cooled to 0 8C and a solution of 1 equiv of the corresponding
dienyl sulfoxide or sulfone in THF (7 mL/mmol), pre-
˚
viously dried over 4 A sieves, was added dropwise. The
reaction mixture was stirred at 0 8C until starting material
disappearance, monitored by TLC. Subsequently, a 10%
solution of Na2S2O4 (4 mL/mmol) and EtOAc (8 mL/mmol)
was added. After separation, the aqueous layer was
extracted with EtOAc (3!10 mL/mmol). The combined
organic extracts were washed with brine and dried with
anhydrous MgSO4. Filtration and evaporation of the solvent
under reduced pressure provided a crude product that was
purified by column chromatography on silica gel.
3.4.1. Synthesis of (L)-(2S,3S,10R)-(E)-3-(10-hydroxy-
pentyl)-2-(1-pentenyl)-2-(p-tolylsulfonyl)oxirane, 10.
From NaH (7 mg, 0.31 mmol) in THF (1.50 mL),
t-BuOOH (40 mL, 35.1 mg, 0.31 mmol) and a solution of
(2!30% EtOAc–hexane). [a]2D0 K17.9 (c 0.41). H NMR
1
(300 MHz) d 0.78 (t, 3H, JZ7.4 Hz), 0.83 (t, 3H, JZ
7.1 Hz), 1.16–1.59 (m, 9H), 1.96 (qd, 2H, JZ7.1, 1.5 Hz),

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R. Fernandez de la Pradilla et al. / Tetrahedron 62 (2006) 2684–2692
2690
2.40 (s, 3H, CH3–p-Tol), 3.33 (dt, 1H, JZ7.9, 5.4 Hz, H-10),
3.67 (d, 1H, JZ8.0 Hz, H-3), 5.43 (dt, 1H, JZ15.6, 1.5 Hz,
H-100), 5.72 (dt, 1H, JZ15.6, 6.8 Hz, H-200), 7.28 (d, 2H, JZ
7.8 Hz, ArH), 7.46 (d, 2H, JZ8.3 Hz, ArH). 13C NMR
(75 MHz) d 13.5, 13.8, 21.5, 21.8, 22.5, 26.8, 33.0, 34.5,
64.6, 69.8, 76.5, 115.1, 125.4 (2C), 129.5 (2C), 136.7,
141.4, 142.2. IR (CCl4): 3360, 2920, 2900, 2820, 1630,
1470, 1440, 1240, 1070, 1000, 770 cmK1. Data for 11a,b (as
an inseparable 44:56 mixture of diastereomers): RfZ0.46
(50% Et2O–hexane). 1H NMR (400 MHz) d 0.88 (t, 3H, JZ
7.3 Hz, CH3), 0.92–1.0 (m, 9H, CH3), 1.23–1.70 (m, 20H),
3.08 (td, 1H, JZ5.9, 1.9 Hz), 3.20–3.26 (m, 3H), 3.39 (d,
1H, JZ1.9 Hz, CH–CO), 3.47 (d, 1H, JZ1.9 Hz, CH–CO),
3.58 (d, 1H, JZ4.8 Hz, CH–CO), 3.77 (d, 1H, JZ4.8 Hz,
CH–CO). 13C NMR (125 MHz) d 13.7, 13.9, 19.1, 19.7,
22.3, 22.4, 26.7, 27.2, 27.8, 28.3, 28.4, 31.4, 31.5, 33.6,
33.7, 56.0, 56.4, 58.6, 58.7, 59.1, 59.3, 59.4, 211.7. IR
(CCl4): 2960, 2930, 2875, 1720, 1460, 1430, 1380, 1230,
1190, 1090, 1050, 1020, 880 cmK1. MS (EI): 212 [M]C,
169, 127, 97, 71, 55 (100%), 43, 41. Data for 11c: RfZ0.52
(50% Et2O–hexane). 1H NMR (400 MHz) d 0.90 (t, 3H, JZ
7.2 Hz), 0.96 (t, 3H, JZ7.2 Hz), 1.34–1.66 (m, 10H), 3.07
(tt, 1H, JZ5.6, 1.7 Hz), 3.16 (td, 1H, JZ5.6, 1.7 Hz), 3.30
(d, 1H, JZ1.9 Hz, CH–CO), 3.42 (d, 1H, JZ2.1 Hz,
CH–CO). 13C NMR (50 MHz) d 13.7, 13.9, 19.1, 22.3,
27.8, 31.5, 33.8, 56.8, 57.2, 57.3, 59.2, 211.7. IR (CCl4):
2960, 2930, 2875, 1720, 1460, 1430, 1380, 1230, 1190,
1090, 1050, 1020, 880 cmK1. MS (EI): 127, 97, 71, 55
(100%), 43, 41, 39. The data of 10 was identical to that
found before.
3.4.5. Synthesis of (D)-(2R,3R,10R,SS)-(E)-3-[10-(tert-
butyldimethylsilyloxy)-n-pentyl]-2-(1-pentenyl)-2-(p-
tolylsulfinyl)oxirane, 13, (2S,3S,10R)-(E)-3-[10-(tert-
butyldimethylsilyloxy)-n-pentyl]-2-(1-pentenyl)-2-(p-
tolylsulfonyl)oxirane, 12, (D)-(2R,3R,10R)-(E)-3-[10-
(tert-butyldimethylsilyloxy)-n-pentyl]-2-(1-pentenyl)-2-
(p-tolylsulfonyl)oxirane, 14. From KH (10.7 mg,
0.26 mmol) in THF (1.30 mL), t-BuOOH (33 mL, 30 mg,
0.26 mmol) and a solution of dienyl sulfoxide 4 (29 mg,
0.06 mmol) in THF (0.46 mL), according to the general
procedure (94 h), a 9:41:37:12 of sulfonyl oxiranes 12 and
14, sulfinyl oxirane 13 and starting material was obtained.
Purification by chromatography (5–15% EtOAc–CH2Cl2)
gave 11.3 mg (38%) of 13, 14 mg (44%) of an 82:18
inseparable mixture of 14 and 12 and 3.1 mg (11%) of
starting material, as colorless oils. Data for 13: RfZ0.45
1
(2!15% EtOAc–hexane). [a]2D0 C80.1 (c 1.11). H NMR
(300 MHz) d K0.06 (s, 3H, TBDMS), K0.02 (s, 3H,
TBDMS), 0.79 (t, 3H, JZ7.4 Hz), 0.85 (s, 9H, TBDMS),
0.87 (t, 3H, JZ7.2 Hz), 1.24–1.51 (m, 8H), 2.00 (q, 2H, JZ
6.8 Hz), 2.37 (s, 3H, CH3–p-Tol), 3.36 (dt, 1H, JZ8.0,
5.6 Hz, H-10), 3.60 (d, 1H, JZ7.9 Hz, H-3), 5.48 (d, 1H, JZ
15.5 Hz, H-100), 5.60 (dt, 1H, JZ15.5, 6.3 Hz, H-200), 7.24
(d, 2H, JZ7.9 Hz, ArH), 7.47 (d, 2H, JZ8.2 Hz, ArH). 13C
NMR (75 MHz) d K4.4, K4.2, 13.6, 14.0, 18.0, 21.5, 21.9,
22.7, 25.7 (3C), 26.3, 34.5, 35.1, 63.8, 68.2, 78.5, 117.1,
125.9 (2C), 129.3 (2C), 136.1, 140.7, 142.0. IR (CCl4):
2920, 2900, 2820, 1530, 1440, 1240, 1060, 990, 770 cmK1
.
Data for 12: RfZ0.48 (15% EtOAc–hexane). 1H NMR
(300 MHz) d K0.04 (s, 3H, TBDMS), 0.05 (s, 3H,
TBDMS), 0.76 (t, 3H, JZ7.3 Hz), 0.80–0.90 (m, 3H),
0.86 (s, 9H, TBDMS), 1.23–1.60 (m, 8H), 1.96 (q, 2H, JZ
6.3 Hz), 2.42 (s, 3H, CH3–p-Tol), 3.22 (dt, 1H, JZ8.1,
4.9 Hz, H-10), 3.77 (d, 1H, JZ8.2 Hz, H-3), 5.65 (dt, 1H,
JZ15.5, 7.0 Hz, H-200), 5.82 (d, 1H, JZ15.5 Hz, H-100),
7.29 (d, 2H, JZ8.4 Hz, ArH), 7.68 (d, 2H, JZ8.4 Hz, ArH).
Data for 14: RfZ0.37 (15% EtOAc–hexane). [a]2D0 C6.6 (c
0.83). 1H NMR (300 MHz) d K0.02 (s, 3H, TBDMS), 0.03
(s, 3H, TBDMS), 0.76 (t, 3H, JZ7.3 Hz), 0.80–0.90 (m,
3H), 0.86 (s, 9H, TBDMS), 1.22–1.39 (m, 6H), 1.52–1.56
(m, 2H), 1.99 (m, 2H), 2.41 (s, 3H, CH3–p-Tol), 3.30 (ddd,
1H, JZ7.9, 6.1, 5.3 Hz, H-10), 3.82 (d, 1H, JZ7.9 Hz, H-3),
5.55 (dt, 1H, JZ15.5, 7.0 Hz, H-200), 5.93 (dt, 1H, JZ15.5,
1.5 Hz, H-100), 7.29 (d, 2H, JZ8.7 Hz, ArH), 7.69 (d, 2H,
JZ8.3 Hz, ArH). 13C NMR (75 MHz) d K4.5, K4.1, 13.5,
14.0, 21.7, 21.8, 22.6, 25.7 (3C), 26.4, 29.7, 34.2, 35.1, 65.1,
67.6, 76.6, 116.5, 129.4 (2C), 129.5 (2C), 132.9, 140.8,
145.5. IR (CCl4): 2920, 2890, 2820, 1440, 1310, 1240,
1130, 1070, 1000, 640 cmK1. MS (APCI): 489 [MCNa]K,
244 (100%).
3.4.4. Synthesis of (D)-(2R,3R,10S,SS)-(E)-3-(10-hydroxy-
pentyl)-2-(1-pentenyl)-2-(p-tolylsulfinyl)oxirane, 15, (D)-
(2R,3R,10S)-(E)-3-(10-hydroxypentyl)-2-(1-pentenyl)-2-
(p-tolylsulfonyl)oxirane ent-10, (7R,8S)-6-oxadodecanyl-
4,7-bis-oxirane, ent-11a,b, (7S,8S)-6-oxado- decanyl-4,
7-bis-oxirane, ent-11c. From NaH (2.2 mg, 0.094 mmol)
in THF (0.47 ), t-BuOOH (12 mL, 11 mg, 0.094 mmol) and
a solution of dienyl sulfoxide 2 (7.5 mg, 0.023 mmol) in
THF (0.16 mL), according to the general procedure
(70 min), an 80:4:11:5 of sulfinyl oxirane 15, sulfonyl
oxirane ent-10, and bis oxiranes ent-11a,b and ent-11c,
was obtained. Purification by chromatography (5–50%
EtOAc–hexane) gave 5.4 mg (76%) of 15, 0.3 mg (4%) of
ent-10 and 0.5 mg (13%) of ent-11c and ent-11a,b as
colorless oils. Data for 15: RfZ0.25 (50% EtOAc–hexane).
[a]2D0 C48.9 (c 0.60). H NMR (300 MHz) d 0.80 (t, 3H,
1
JZ7.4 Hz), 0.87 (t, 3H, JZ7.2 Hz), 1.20–1.39 (m, 6H),
1.36–1.62 (m, 2H), 1.81 (d, 1H, JZ2.4 Hz, OH), 1.99 (qd,
2H, JZ7.0, 1.5 Hz), 2.39 (s, 3H, CH3–p-Tol), 3.35 (m, 1H,
H-10), 3.61 (d, 1H, JZ8.1 Hz, H-3), 5.40 (dt, 1H, JZ15.7,
1.5 Hz, H-100), 5.67 (dt, 1H, JZ15.7, 6.8 Hz, H-200), 7.26
3.4.6. Synthesis of (L)-(2S,3R,10S)-(E)-3-(10-hydroxy-
pentyl)-2-(1-pentenyl)-2-(p-tolylsulfonyl)oxirane, 17.
From NaH (3.7 mg, 0.15 mmol) in THF (0.80 mL),
t-BuOOH (19 mL, 17 mg, 0.15 mmol) and a solution of
dienyl sulfone 7 (13 mg, 0.038 mmol) in THF (0.26 mL),
according to the general procedure (55 min), sulfonyl
oxirane 17 was obtained. Purification by chromatography
(5–50% Et2O–hexane) gave 11 mg (82%) of 17, as a
colorless oil. Data for 17: RfZ0.28 (50% Et2O–hexane).
[a]2D0 K39.2 (c 0.76). 1H NMR (300 MHz) d 0.68 (t, 3H, JZ
7.4 Hz), 0.92 (t, 3H, JZ7.3 Hz), 1.18 (sext, 2H, JZ7.3 Hz),
1.34–1.54 (m, 4H), 1.65–1.69 (m, 2H), 1.81–1.90 (m, 2H),
(d, 2H, JZ7.9 Hz, ArH), 7.46 (d, 2H, JZ8.2 Hz, ArH). 13
C
NMR (50 MHz) d 13.5, 13.8, 21.5, 21.8, 22.5, 26.9, 33.0,
34.5, 64.5, 69.8, 78.8, 117.4, 126.1 (2C), 129.3 (2C), 135.6,
141.1, 142.3. IR (CCl4): 3350, 2920, 2890, 2820, 2840,
1730, 1540, 1470, 1450, 1380, 1240, 1070, 1000, 770,
640 cmK1. Anal. Calcd for C19H28O3S: C, 67.82; H, 8.39;
S, 9.53. Found: C, 67.65; H, 8.42; S, 9.44. The data for
ent-10, ent-11c and ent-11a,b was identical to that of their
enantiomers.

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R. Fernandez de la Pradilla et al. / Tetrahedron 62 (2006) 2684–2692
2691
2.32 (d, 1H, JZ3.6 Hz, OH), 2.42 (s, 3H, CH3–p-Tol), 3.04
(d, 1H, JZ7.8 Hz, H-3), 4.62 (m, 1H, H-10), 5.59 (dt, 1H,
JZ15.5, 6.6 Hz, H-200), 5.73 (dt, 1H, JZ15.5, 1.2 Hz,
H-100), 7.31 (d, 2H, JZ7.9 Hz, ArH), 7.71 (d, 2H, JZ
8.3 Hz, ArH). 13C NMR (75 MHz) d 13.3, 14.0, 21.5, 21.7,
22.5, 27.0, 33.6, 33.8, 67.7, 73.1, 76.8, 120.5, 129.1 (2C),
129.5 (2C), 134.4, 138.1, 145.2. IR (CCl4): 3500, 2920,
2900, 2830, 1640, 1580, 1450, 1310, 1240, 1150, 1060, 990,
780, 660 cmK1. Anal. Calcd for C19H28O4S: C, 64.74; H,
8.01; S, 9.10. Found: C, 64.66; H, 8.25; S, 9.01.
3.4.10. Synthesis of (D)-(2R,3S,10S)-(E)-3-(10-hydroxy-
pentyl)-2-(1-pentenyl)-2-(p-tolylsulfonyl)oxirane, ent-10.
From sulfinyl oxirane 15 (6 mg, 0.017 mmol) in MeOH
(0.17 mL) and MMPP (16.5 mg, 0.026 mmol), according to
the general procedure (90 min), after chromatography
(5–30% EtOAc–hexane), sulfonyl oxirane ent-10 (3.5 mg,
59%) was obtained as a colorless oil with data identical to
that of its enantiomer except for the sign of the optical
rotation ([a]2D0 C32.6 (c 0.35)).
3.4.11. Synthesis of (L)-(2S,3R,10S)-(E)-3-(10-hydroxy-
pentyl)-2-(1-pentenyl)-2-(p-tolylsulfonyl)oxirane, 17.
From sulfinyl oxirane 16 (10.8 mg, 0.032 mmol) in MeOH
(0.32 mL) and MMPP (29.8 mg, 0.048 mmol), according to
the general procedure (23 h), after chromatography (5–20%
EtOAc–hexane), sulfonyl oxirane 17 (7.0 mg, 62%) was
obtained as a colorless oil with data identical to that found
before.
3.4.7. Synthesis of (D)-(2S,3R,10S,SS)-(E)-3-(10-hydroxy-
pentyl)-2-(1-pentenyl)-2-(p-tolylsulfinyl)oxirane, 16, (L)-
(2S,3R,10S)-(E)-3-(10-hydroxypentyl)-2-(1-pentenyl)-2-
(p-tolylsulfonyl)oxirane, 17, (7S,8S)-6-oxadodecanyl-4,
7-bis-oxirane, ent-11c, (7R,8S)-6-oxadodecanyl-4,7-bis-
oxirane, ent-11a,b. From NaH (9.9 mg, 0.41 mmol) in
THF (2.0 mL), t-BuOOH (51 mL, 46 mg, 0.41 mmol) and a
solution of dienyl sulfoxide 3 (33 mg, 0.102 mmol) in THF
(0.71 mL), according to the general procedure (45 min) a
65:4:18:2:11 mixture of 16, 17, ent-11c, ent-11a,b and 3
was obtained. Purification by chromatography (5–50%
Et2O–hexane, then 5–20% EtOAc–toluene) gave 14.8 mg
(44%) of sulfinyl oxirane 16, 1 mg (3%) of sulfonyl oxirane
17, 3 mg (14%) of bis oxiranes ent-11c and ent-11a,b and
3 mg (10%) of starting material, as colorless oils. Data for
16: RfZ0.30 (2!30% EtOAc–hexane). [a]2D0 C7.3 (c
Acknowledgements
This research was supported by CAM (GR/SAL/0823/2004)
and DGICYT (BQU2003-02921). We thank JANSSEN-
CILAG for generous additional support and CAM for a
doctoral fellowship to C.M.
References and notes
1
1.17). H NMR (300 MHz) d 0.71 (t, 3H, JZ7.4 Hz), 0.94
1. (a) Ooi, T.; Ohara, D.; Tamura, M.; Maruoka, K. J. Am. Chem.
Soc. 2004, 126, 6844–6845. (b) Nemoto, T.; Kakei, H.;
Gnanadesikan, V.; Tosaki, S.; Ohshima, T.; Shibasaki, M.
J. Am. Chem. Soc. 2002, 124, 14544–14545. For a review, see:
Lauret, C.; Roberts, S. M. Aldrichim. Acta 2002, 35, 47–51.
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12, 2359–2383. For leading references, see: (b) Chen, W. P.;
Roberts, S. M. J. Chem. Soc., Perkin Trans. 1 1999, 103–105. (c)
Kakei, H.; Nemoto, T.; Ohshima, T.; Shibasaki, M. Angew.
Chem., Int. Ed. 2004, 43, 317–320. (d) Tosaki, S.; Nemoto, T.;
Ohshima, T.; Shibasaki, M. Org. Lett. 2003, 5, 495–498.
(t, 3H, JZ7.3 Hz), 1.21 (sext, 2H, JZ7.4 Hz), 1.40–1.84
(m, 6H), 1.90 (q, 2H, JZ7.0 Hz), 2.10 (br s, 1H, OH), 2.38
(s, 3H, CH3–p-Tol), 3.13 (d, 1H, JZ8.2 Hz, H-3), 4.16
(dt, 1H, JZ8.0, 5.5 Hz, H-10), 5.51 (dt, 1H, JZ15.5, 6.8 Hz,
H-200), 5.74 (dt, 1H, JZ15.6, 1.5 Hz, H-100), 7.27 (d, 2H,
JZ7.9 Hz, ArH), 7.46 (d, 2H, JZ8.3 Hz, ArH). 13C NMR
(75 MHz) d 13.4, 13.9, 21.4, 21.7, 22.6, 27.0, 33.3, 34.1,
69.9, 71.2, 76.4, 116.6, 125.1 (2C), 129.4 (2C), 136.1,
138.6, 141.8. IR (CCl4): 3360, 2930, 2900, 2840, 1720,
1640, 1580, 1470, 1450, 1360, 1240, 1060, 1020, 990,
770 cmK1. Anal. Calcd for C19H28O3S: C, 67.82; H,
8.39; S, 9.53. Found: C, 67.98; H, 8.56; S, 9.71. The
data for 17, ent-11c, and ent-11a,b was identical to those
found before.
´
3. (a) Fernandez de la Pradilla, R.; Castro, S.; Manzano, P.;
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Fernandez de la Pradilla, R.; Castro, S.; Manzano, P.;
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Martın-Ortega, M.; Priego, J.; Viso, A.; Rodrıguez, A.;
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4. (a) Fernandez de la Pradilla, R.; Manzano, P.; Priego, J.;
3.4.8. Synthesis of (2S,3S,10R)-(E)-3-[(10-t-butyldimethyl-
silyloxy)-n-pentyl]-2-(1-pentenyl)-2-(p-tolylsulfonyl)-
oxirane, 12. From hydroxy sulfonyl oxirane 10 (12.4 mg,
0.03 mmol) in CH2Cl2 (0.30 mL), imidazole (2.9 mg,
0.042 mmol), t-butyldimethylsilyl chloride (6 mg,
0.038 mmol) according to the general procedure (25 h),
after chromatography (5–30% EtOAc–hexane), 4.5 mg
(29%) of silylated oxirane 12 and 8.75 mg (70%) of starting
material, was obtained as colorless oils. The data for 12 was
identical to those found before.
´
Viso, A.; Rodrıguez, A. Tetrahedron Lett. 1996, 37,
´ ´
6793–6796. (b) Fernandez de la Pradilla, R.; Fernandez, J.;
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Manzano, P.; Mendez, P.; Priego, J.; Tortosa, M.; Viso, A.;
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Martınez-Ripoll, M.; Rodrıguez, A. J. Org. Chem. 2002, 67,
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5. Fernandez de la Pradilla, R.; Buergo, M. V.; Manzano, P.;
´ ´
Montero, C.; Priego, J.; Viso, A.; Cano, F. H.; Martınez-Alcazar,
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6. For a review on the preparation and applications of a-oxy
sulfones, including sulfonyl oxiranes, see: (a) Chemla, F.
J. Chem. Soc., Perkin Trans. 1 2002, 275–299. For other
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3303–3325. For recent references on applications of sulfinyl
and sulfonyl oxiranes, see: (d) For an application of these
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and Adriatoxin, see: Mori, Y.; Takase, T.; Noyori, R.
3.4.9. Synthesis of (D)-(2R,3R,10R)-(E)-3-[(10-tert-butyl-
dimethylsilyloxy)-n-pentyl]-2-(1-pentenyl)-2-(p-tolyl-
sulfonyl)oxirane, 14. From sulfinyl oxirane 13 (11 mg,
0.02 mmol) in MeOH (0.24 mL) and MMPP (22.7 mg,
0.036 mmol), according to the general procedure (2 h), after
chromatography (5–30% EtOAc–hexane), sulfonyl oxirane
14 (8.3 mg, 74%) was obtained as a colorless oil. The data
for 14 was identical to those found before.

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R. Fernandez de la Pradilla et al. / Tetrahedron 62 (2006) 2684–2692
2692
Tetrahedron Lett. 2003, 44, 2319–2322. (e) For an application
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11. A similar effect was observed by Jackson, see: Jackson,
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´
and Kumausallene, see: Fernandez de la Pradilla, R.;
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Viso, A. Tetrahedron Lett. 1997, 38, 7773–7776. (b) Fernandez
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