Diastereoselective synthesis of γ-hydroxy α,β-epoxyesters and their conversion into β-hydroxy α-sulfenyl γ-butyrolactones

Article abstract of DOI:10.1016/j.tet.2006.09.030

The diastereoselectivity of the nucleophilic epoxidation of γ-hydroxy-α,β-unsaturated esters has been studied. The γ-hydroxy-α,β-unsaturated esters were obtained through treatment of ethyl (E)-4-oxo-2-butenoate with the corresponding Grignard reagent and

Full text of DOI:10.1016/j.tet.2006.09.030

Tetrahedron 62 (2006) 11112–11123
Diastereoselective synthesis of g-hydroxy a,b-epoxyesters and
their conversion into b-hydroxy a-sulfenyl g-butyrolactones
a,
Santiago Rodrıguez, Marıa Kneeteman, Javier Izquierdo, Irakusne Lopez,
a
a
a
*
´
´
Florenci V. Gonzalez and Gabriel Peris
ꢀ
a,
b
*
ꢀ
a
´
ꢁ
ꢁ
ꢀ
Departament de Quımica Inorganica i Organica, Universitat Jaume I, 12080 Castello, Spain
b
´
Serveis Centrals d’Instrumentacioꢀ Cientıfica, Universitat Jaume I, 12080 Castello, Spain
ꢀ
Received 17 July 2006; revised 26 August 2006; accepted 12 September 2006
Available online 9 October 2006
Abstract—The diastereoselectivity of the nucleophilic epoxidation of g-hydroxy-a,b-unsaturated esters has been studied. The g-hydroxy-
a,b-unsaturated esters were obtained through treatment of ethyl (E)-4-oxo-2-butenoate with the corresponding Grignard reagent and were
used as a racemic mixture. The resulting g-hydroxy a,b-epoxyesters were treated with thiophenol for transformation into a-phenylsulfanyl
trisubstituted g-butyrolactones. The syn,syn-lactones isomerize easily in basic media into the syn,anti structures. In order to explain this
interconversion, a retroaldol–aldol sequence has been proposed and a sulfur–oxygen interaction has been invoked to explain the syn
stereochemical preference of the a-sulfured aldols resulting from the intramolecular aldol reaction.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
a-phenylsulfanyl g-butyrolactones 4/5 was useful for the
stereochemical determination of the preceding epoxyesters
(Scheme 1). Trisubstituted g-butyrolactones are an interest-
ing family of compounds,4 which could be then obtained
starting from chiral g-hydroxy a,b-epoxyesters.
a,b-Epoxyesters are versatile functionalities in organic syn-
thesis since they can be converted into interesting synthetic
compounds through the opening of the oxirane ring.1 The
most convenient method for their preparation is through ep-
oxidation of unsaturated esters using a hydroperoxide in the
presence of a base.2 A deeper understanding of the stereo-
selectivity of the epoxidation of unsaturated esters would in-
crease the synthetic applications of these intermediates. We
previously reported the influence of solvent and temperature
on the epoxidation of g-hydroxy-a,b-unsaturated esters3 and
now wish to report a general study of this reaction including
a correction of the previous stereochemical assignment of
some of the resulting epoxides.
The stereoselectivity of the epoxidation reactions was mea-
sured as the ratio between syn/anti diastereomers 2 and 3
(Scheme 1) and must be interpreted as a conjugate addition
to an unsaturated ester modulated by a stereocenter in the
g-position.5
2. Results
2.1. Preparation of substrates
In this paper we also show that the thiophenol-mediated
transformation of the g-hydroxy a,b-epoxyesters into
We wanted to study the selectivity of epoxidation of
g-hydroxy-a,b-unsaturated esters with a range of R alkyl
SPh
O
HO
O
R
O
OEt
O
4 syn-syn
O
OH
R
PhSH
2 syn
R
+
O
OEt
O
M
SPh
OH
HO
O
O
1
R
O
O
OEt
R
OH
3 anti
5 syn-anti
Scheme 1. General scheme of reactions.
Keywords: Diastereoselective epoxidation; Epoxyesters; Lactonization; g-Butyrolactones.
* Corresponding authors. Tel.: +34 964728241; fax: +34 964728214 (F.V.G.); e-mail: fgonzale@qio.uji.es
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.09.030

´
S. Rodrıguez et al. / Tetrahedron 62 (2006) 11112–11123
11113
groups. Commonly g-hydroxy-a,b-unsaturated esters are
obtained in enantiopure form through Wittig–Horner
reaction of chiral aldehydes or enzymatic resolutions of
the corresponding racemic mixtures,6 we synthesized the
g-hydroxy-a,b-unsaturated esters through treatment of ethyl
(E)-4-oxo-2-butenoate3 with the corresponding Grignard
reagent and they were used as a racemic mixture in the
epoxidation process (Scheme 2).
product. The syn/anti assignment for 2b/3b represents a
correction to our previous work,3 an explanation for which
is provided subsequently.
These results showed that stereoselectivity does not depend
on the nature of the pendant R alkyl group for all g-hydroxy-
a,b-unsaturated esters examined.
In order to study the influence of the temperature over the
stereoselectivity, we carried out the epoxidation reaction of
compound 1b at different temperatures (Table 2).
O
O
R
H
a
OEt
OEt
OH
O
Table 2 shows that there is no temperature dependence since
the diastereomeric ratios at different temperatures in a range
between ꢀ80 and 50 ꢁC are same within experimental error.
1a, R=Ph
1b, R=Me
1c, R=i-Propyl
1d, R=i-Pentyl
1e, R=n-Butyl
1f, R=Chx
1g, R=p-MeOPh
1h, R=t-Butyl
Similar J3,4 coupling constants were observed for diastereo-
mers syn a,b-epoxyesters 2a–h and also for anti a,b-epoxy-
esters 3a–h (Table 3). For syn isomers, J3,4 values were
between 3.5 and 4.5 Hz whilst for the anti form, J3,4 ranged
from 2.5 to 3.5 Hz.
Scheme 2. Preparation of g-hydroxy-a,b-unsaturated esters: (a) RMgBr,
THF, ꢀ78 ꢁC–0 ꢁC.
Thus, the measurement of J3,4 represented a convenient
method for the stereochemical assignment of these com-
pounds whenever both isomers were available.
We also prepared O-protected a,b-unsaturated esters in
order to study the influence of the hydroxyl protecting group
on the epoxidation. These compounds were synthesized
through protection of compound 1b via standard conditions
(Scheme 3).
We also epoxidized compound 1b by using oxidants other
than lithium tert-butylperoxide (Table 4).
O
O
a
H3C
Table 2. Epoxidation of 1b at different temperatures
H3C
OEt
OEt
O
O
O
OH
OP
O
O
TBPLi
THF
Me
Me
Me
1b
+
OEt
OEt
OEt
2b syn
2b:3ba
6a, P=TPS
6b, P=TIPS
6c, P=MOM
OH
OH
OH
3b anti
1b
Entry
T (ꢁC)/t (h)
Yield (%)
Scheme 3. Protection of g-hydroxy-a,b-unsaturated esters: (a) P–Cl, base.
1
2
3
4
5
6
7
ꢀ80/72
ꢀ60/46
ꢀ40/24
ꢀ20/20
0/14
73:27
78:22
77:23
70:30
74:26
78:22
76:24
30
55
54
60
55
52
45
2.2. Epoxidation of g-hydroxy-a,b-unsaturated ethyl
esters
Esters 1 were epoxidized using lithium tert-butylperoxide as
the oxidizing reagent in THF as solvent at ꢀ20 ꢁC. Table 1
shows that the diastereomeric ratios are similar for all condi-
tions examined, furnishing the 2 syn isomer as the major
25/3
50/5
Ratio measured by 13C NMR of the crude reaction mixtures.
a
Table 1. Epoxidation of g-hydroxy-a,b-unsaturated esters using lithium
tert-butylperoxide
Table 3. Coupling constants of epoxyalcohols
O
O
O
O
O
O
2
O
O
O
2
3
3
TBPLi, THF
-20 °C, 20h
R
4
R
4
R
R
R
OEt
OEt
OEt
OEt
1
OEt
1
+
OH
OH
OH
OH
OH
2 syn
3 anti
2 syn
3 anti
Entry
Substrate
R
T (ꢁC)/t (h)
2:3a
Yield (%)
R
J3,4 2 syn (Hz)
J3,4 3 anti (Hz)
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
Ph
Me
i-Pr
i-Pent
n-Bu
Chx
p-MeOPh
t-Bu
ꢀ20/20
ꢀ20/20
ꢀ20/20
ꢀ20/20
ꢀ20/20
ꢀ20/15
ꢀ20/15
ꢀ20/72
80:20
70:30
80:20
78:22
81:19
76:24
77:23
70:30
78
60
55
44
48
47
69
41
Ph
Me
i-Pr
i-Pent
n-Bu
Chx
p-MeOPh
t-Bu
4.5
4.2
4
4
4
4
4.5
3.5
2.5
3.1
3
3.5
a
3
2.5
2.5
1g
1h
Ratio measured by 13C NMR of the crude reaction mixtures.
Coupling constant could not be measured because of overlapping signals.
a
a

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S. Rodrıguez et al. / Tetrahedron 62 (2006) 11112–11123
11114
Table 4. Epoxidation of ester 1b using other conditions
Entry
Reagent
Solvent
T (ꢁC)/t
2b:3bb
Yield (%)
1
2
3
4
5
6
7
8
TBHP, EtLi
THF
THF
THF
THF/HMPA
THF/DMF
CH2Cl2
THF
THF
THF
THF
THF
CH2Cl2
THF
THF
CH2Cl2
CH2Cl2
Hexanes
Toluene
ꢀ20/20 h
ꢀ20/60 h
ꢀ20/20 h
ꢀ20/20 h
ꢀ20/20 h
0 ꢁC/120 h
ꢀ20/20 h
Rt/1.5 h
ꢀ20/20 h
ꢀ80/72 h
ꢀ20/20 h
0/4 days
Rt/6 days
ꢀ20/20 h
ꢀ20/4 days
Rt/20 h
70:30
81:19
88:12
88:12
85:15
20:80
—
56:44
79:21
68:32
62:38
40:60
—
60
TBHP, EtLi, 12-cr-4a
TBHP, EtLi, TMEDAa
TBHP, EtLi
39
50c
42
TBHP, EtLi
51
TBHP, Et2Zna
TBHP, Bu2Mg
TBHP, NaH
15c
N.R.
22
9
TBHP, NaH
TBHP, NaH
TBHP, KH
TBHP, Ti(O-i-Pr)4
TBHP, EtLi, Ti(O-i-Pr)4
CMHP, EtLi
18
25
30
10
11
12
13
14
15
16
17
18
74c
N.R.
65
77:23
67:33
—
46:54
68:32
m-CPBA
70c
N.R.
25
m-CPBA, K2CO3
TBHP, EtLi
TBHP, EtLi
ꢀ20/20 h
ꢀ20/20 h
53
a
12-Cr-4 (2.5 equiv) was used in entry 2; 2 equiv of TMEDA were used in entry 3; 1.1 equiv of Et2Zn were used in entry 6.
Ratio measured by 13C NMR of the crude reaction mixtures.
Starting material was recovered: 31% for entry 3; 29% for entry 6; 50% for entry 12; 25% for entry 15.
b
c
If the reaction was carried out using lithium tert-butylper-
O-Protected unsaturated esters 6 were subjected to epoxida-
tion using lithium tert-butylperoxide (Table 5).
oxide in the presence of a cation scavenger (entries 2 and
3) or in a more polar solvent (entries 4 and 5), then a better
selectivity was observed. On the other hand, in the alkaline
peroxides series, potassium gave poorer stereoselectivity
than either lithium or sodium (entries 1 and 8–11). The
anti isomer predominated when zinc7 peroxide was used,
as opposed to the selectivity achieved using alkaline cations.
Magnesium8 (entry 7) was not reactive. When titanium
isopropoxide (entry 12) was used, starting material was
recovered and stereoselectivity was poor, furnishing the
anti isomer as the major product. The reaction using lithium
tert-butylperoxide and titanium isopropoxide (entry 13) did
not give reaction product.
All the O-protected esters (6a–c) were less reactive than free
compound 1b since the epoxidation reactions took longer
time (a few days for all cases). The triisopropylsilyl protect-
ing group gave the best selectivity, furnishing the syn isomer
7 as the major one.
Studies to rationalize the stereoselectivity of these epoxida-
tion reactions are currently underway in our laboratory.
2.3. Synthesis of g-butyrolactones
The g-hydroxy a,b-epoxyesters 2/3 were treated with thio-
phenol in the presence of a base resulting in the opening
of the oxirane ring. The products derived from these reac-
tions were the corresponding g-butyrolactones 4/5 or the
diols 9/10 depending on the conditions and the substrate
(Table 6).
Lithium cumylperoxide gave the same result as lithium tert-
butylperoxide (entry 14). The rate of the epoxidation using
m-CPBA9 (entry 15) was slower than with the other
oxidants, affording the syn isomer as the major one. When
m-CPBA was used in the presence of potassium carbonate10
(entry 16), only starting material was recovered.
When epoxides 2a/3a (from entry 1, Table 1) were treated
with thiophenol in the presence of triethylamine at room
temperature for 1 h, only diols 9a/10a were obtained (entry
1, Table 6) but with longer time, partial cyclization of diols
furnished lactones 4a/5a (entry 2, Table 6) in 1:1 ratio. This
mixture of diols and lactones was directly subjected to acid
treatment, furnishing a mixture of diastereomeric lactones
with lactone 4a being the major one (Table 7).
If the reaction was carried out using lithium tert-butylper-
oxide in non-polar solvents (entries 17 and 18) then a poor
selectivity was observed.
Table 5. Epoxidation of O-protected-g-hydroxy-a,b-unsaturated esters
O
O
O
O
TBPLi
THF
When epoxides 2b/3b (from entry 2, Table 1) were treated
with thiophenol and triethylamine in acetonitrile, diol 9b,
lactones 4b/5b in 1:1 ratio, and butenolide 11b derived
from dehydration of the lactones were obtained (entry 3, Ta-
ble 6). When the reaction was performed in methanol instead
of acetonitrile for longer time (entry 4), only lactones were
obtained and, surprisingly, 5b was the major lactone, thus
showing opposite stereoselection to 2a/3a.
H3C
H3C
+
6
OEt
OEt
OP
OP
7
8
Entry
T (ꢁC)/t
6
7:8a
Yield (%)
1
2
3
4
Rt/5 days
2/10 days
6a
55:45
81:19
84:16
63:37
50
6b
6b
6c
56
ꢀ20/100 h
75b
47b
ꢀ20/5 days
Ratio measured by 13C NMR of the crude reaction mixtures.
Starting material was recovered: 50% for entry 3; 44% for entry 4.
a
A similar result was obtained using Sharpless conditions with
sodium thiophenolate buffered with thiophenol11 (entry 5).
b

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S. Rodrıguez et al. / Tetrahedron 62 (2006) 11112–11123
11115
Table 6. Treatment of epoxyesters 2/3 with thiophenol
SPh
O
SPh
OH
O
SPh
O
O
OH
O
HO
R
HO
R
O
O
R
PhSH
base
R
R
R
O
OEt
OEt
OEt
OEt
+
O
O
OH SPh
R
O
O
OH
OH
OH SPh
2 syn
3 anti
4
5
9
10
11
Entry
Substrate
T (ꢁC)/t
Reagents
4
5
9
10
11
Yield (%)
65
—
1
2
3
4
5
6
7
8
2a/3a (R¼Ph)
2a/3a (R¼Ph)
2b/3b (R¼Me)
2b/3b (R¼Me)
2b/3b (R¼Me)
2b/3b (R¼Me)
2b/3b (R¼Me)
2c/3c (R¼i-Pr)
2c/3c (R¼i-Pr)
2c (R¼i-Pr)
Rt/1 h
Rt/16 h
0/450
Rt/6 h
Rt/2 h
rt/1 h
ꢀ40/800
Rt/22 h
Rt/1 h
Rt/2 h
Rt/2 h
Rt/2 h
PhSH/Et3N/CH3CN
PhSH/Et3N/CH3CN
PhSH/Et3N/CH3CN
PhSH/Et3N/MeOH
PhSH/PhSNa/THF
PhSH/PhSNa/THF
PhSH/PhSNa/THF
PhSH/Et3N/CH3CN
PhSH/PhSNa/THF
PhSH/PhSNa/THF
PhSH/PhSNa/THF
PhSH/PhSNa/THF
9a (75)
9a (50)
9b (28)
10a (25)
10b (28)
a
4a (25)
4b (19)
4b (32)
4b (37)
4b (21)
5a (25)
5b (23)
5b (68)
5b (63)
5b (33)
11b (30)
11c (7)
43
55
50
a
9b (46)
9b (72)
9c (57)
—
67
45
89
70
66
77
4c (19)
4c (33)
4c (40)
4e (34)
4f (34)
5c (17)
5c (67)
5c (60)
5e (66)
5f (66)
9
10
11
12
2e/3e (R¼n-Bu)
2f/3f (R¼Chx)
a
Crude oil was directly subjected to acid cyclization (see Table 6).
When this reaction was conducted for shorter time (entry 6),
diol 9b and a mixture of lactones were obtained and at low
temperature (entry 7) diols 9b/10b were obtained, furnishing
9b as the major one. The mixture of diols and lactones ob-
tained from entry 6 was directly subjected to acid treatment
(Table 6), furnishing 4b/5b but 4b being the major product,
a result opposite to that for entries 4 and 5.
and H-3, whilst the lactone 4b gave NOE between the
methyl and OH but not between the methyl and H-2. 4c
and 4f gave NOE between the H-2 and H-4 whilst 5c H-2
gave NOE with the isopropylic hydrogen.
NOE
H
H
NOE
H
SPh
O
H
HO
H
SPh
O
HO
H
SPh
O
2
HO
H
2
3
NOE
4
O
O
The results obtained with epoxides 2c/3c were similar to 2b/
3b. When epoxides 2c/3c (entry 3, Table 1) were treated with
thiophenol and triethylamine in acetonitrile, then diol 9c
and lactones 4c/5c were obtained along with butenolide
11c (entry 8). Using sodium thiophenolate, the result was
also similar to 2b/3b, yielding lactones 4c/5c (entry 9).
Curiously, a mixture of 4c/5c was obtained when the sub-
strate was pure major epoxyester (entry 10).
H3C
O
Ph
R
4c,f
4a
4b
SPh
HO
NOE
H
H
2
H
SPh
HO
2
3
O
H
NOE
H
H3C
NOE
H
O
O
O
5b
5c
The reaction of epoxides 2e/3e and 2f/3f (entries 5 and 6,
Table 1) with sodium thiophenolate gave a similar result to
the other epoxides, furnishing a mixture of lactones 4/5 in
34:66 ratio for both cases (entries 11 and 12).
The X-ray crystal structures of 4a–c confirmed definitively
the stereochemistry of syn,syn-lactones.12 The conformation
of all three g-butyrolactones in the X-ray structures is very
similar, having the R alkyl groups and the thiophenyl substit-
uents in equatorial position and the hydroxyl groups in axial
position (Fig. 1).
2.4. Stereochemical determination of lactones 4/5 and
diols 9/10
In comparing the shifts of the ring protons and ring 13C
nuclei for all lactones (Table 8) some similarities were
observed: syn,anti-lactones 5 show H2 upfield shift with re-
spect to the syn,syn 4, while H3 and H4 appear downfield in 5
with respect to 4, and C2 appears shifted upfield for 5 while
C4 appears downfield in 5 in relation to 4.13
The stereochemical assignment of the lactones was per-
formed by NOE experiments. Lactone 4a gave NOE be-
tween H-2 and H-4 whilst 5a did not. Lactone 5b gave
NOE between the methyl and H-2 and between the methyl
Table 7. Cyclization of diol 9 in acidic media
The resulting diols from these reactions were transformed
into cyclic carbonates: the mixture of diols 9a/10a (from
entry 1, Table 6) and 9b/10b (from entry 7, Table 6) was
submitted to reaction with triphosgene giving carbonates
12a/13a and 12b/13b, respectively (Table 9).
SPh
SPh
HO
R
HO
R
CSA, benzene
1.5 h, reflux
4 + 5 + 9
O
+
O
O
5
O
4
Entry
Substrate
4:5
Yield (%)
The stereochemistry of the carbonates was assigned by
NMR: coupling constants (J4,5 for 13, higher than for 12)
and by NOE experiments.
1
2
Entry 2, Table 6
Entry 6, Table 6
76:24
65:35
57
45

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S. Rodrıguez et al. / Tetrahedron 62 (2006) 11112–11123
11116
NOE
O
O
O
H
O
O
H
O
4 5
4 5
H
H3C
Ph
CO2Et
SPh
CO2Et
SPh
H
H
NOE
NOE
12a
12b
X-ray structure of 4a
(J4,5=5Hz)
O
(J4,5=4,5Hz)
O
O
O
O
O
4
4 5
5
Ph
H3C
CO2Et
CO2Et
PhS
13b
PhS
13a
(J4,5=7Hz)
(J4,5=7Hz)
X-ray structure of 4b
We have also assured the stereochemical assignment of 2b/
3b by reduction of epoxyketone 14 using zinc borohydride.
As expected, the reduction of an epoxyketone using zinc
borohydride gave the anti isomer as the major one14
(Scheme 4).
O
O
O
b
CO2Et
a
H3C
CO2Et
H3C
CO2Et
3b
H3C
2b/3b
+
OH
OH
81%
14
2b
O
X-ray structure of 4c
19%
Figure 1. X-ray structures of lactones 4a, 4b, and 4c.
Scheme 4. Reduction of compound 14: (a) Dess–Martin, 70%; (b)
Zn(BH4)2, 75%.
The NMR spectra of the major isomer were identical to the
minor in the 2b/3b mixture derived from the epoxidation
(entry 2, Table 1). The major diastereomer in 2b/3b mixture
was the syn one, correcting the stereochemical assignment
we previously published.3
Table 8. 1H and 13C NMR shifts of lactones 4 and 5
SPh
SPh
HO
R
HO
R
2
2
3
4
3
4
O
O
O
5
O
4
2.5. Stereochemical determination of O-protected
epoxides
Lactone
d H2
d H3
d H4
d C2
d C3
d C4
4a (R¼Ph)
5a (R¼Ph)
4b (R¼Me)
5b (R¼Me)
4c (R¼i-Pr)
5c (R¼i-Pr)
4e (R¼n-Bu)
5e (R¼n-Bu)
4f (R¼Chx)
5f (R¼Chx)
4.25
3.89
4.24
3.81
4.25
3.80
4.18
3.73
4.16
3.72
4.46
4.39
4.24
4.31
4.31
4.35
4.20
4.23
4.23
4.29
5.37
5.50
4.51
4.65
3.86
4.06
4.26
4.35
3.88
4.06
56.5
52.2
57.3
53.0
57.6
53.5
56.9
52.9
57.5
53.3
83.0
83.3
79.0
78.7
88.3
88.4
83.2
83.2
87.1
87.0
71.4
75.5
69.9
74.7
68.6
74.0
69.4
74.3
68.3
73.8
The stereochemistry of the O-silyl protected epoxides (7a–c/
8a–c) was established through deprotection affording the
known epoxides 2b/3b (Scheme 5).
O
O
O
O
a
H3C
H3C
OEt
OEt
OP
OH
7a-b/8a-b
2b/3b
Scheme 5. Deprotection of O-silyl protected epoxides: (a) TBAF, THF.
In case of the O-methoxymethyl protected epoxides, the
stereochemistry was established through treatment with
thiol and Lewis acid,15 which furnished lactone 4b and
butenolide 13b (Scheme 6).
Table 9. Cyclization of diols 9/10
O
O
O
triphosgene
O
O
O
9 + 10
+
py
SPh
SPh
R
R
CO2Et
12
CO2Et
13
HO
PhS
a
PhS
7c/8c
O
O
+
H3C
(63/37)
O
O
4b
H3C
Entry
Diols (9/10)
12
13
Yield (%)
13b
50%
50%
1
2
Entry 1, Table 6
Entry 7, Table 6
12a (75)
12b (72)
13a (25)
13b (28)
65
42
Scheme 6. Deprotection of epoxides 7c/8c: (a) PhSH, BF3$Et2O, 70%.

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S. Rodrıguez et al. / Tetrahedron 62 (2006) 11112–11123
11117
3. Discussion
Both lactones 4 and 5 show a 2,3-syn relationship as the syn-
ketones in Scheme 9.
We were unable to make a definitive assignment for the
stereochemistry of epoxides 2b/3b since carbonates and
lactones obtained in acidic media would yield as the major
epoxide 2b (same stereoselectivity as epoxides 2a/3a) but
for lactones obtained in basic media, the major isomer would
be 3b, as can also be said for 2c/3c.
This tendency of a-hydroxy thiols derived from an intra-
molecular aldol reaction to be syn could be explained by
a sulfur–oxygen interaction;17 this interaction over the
enolate–aldehyde would orientate the aldehyde and the
sulfured enolate in the syn position. A similar sulfur–oxygen
interaction has been invoked between the carbonylic oxygen
and the thiolic sulfur of 2-mercaptoacetophenones.17b The
stereochemical outcome in the intramolecular aldol reaction
would then be controlled by two factors: a steric factor about
3,4-anti relationship in 5 and an S–O interaction about
2,3-syn relationship in both 4 and 5.
We believe that an isomerization of lactone 4 into lactone 5
occurs during the opening of the epoxides under basic
conditions (entries 4 and 5, 9–12 of Table 6). To confirm
this speculation, pure lactone 4c was treated with triethyl-
amine at room temperature and a 4:6 mixture of 4c and 5c
was obtained (Scheme 7).
SPh
SPh
4. Conclusions
HO
HO
a
O
O
+
4c
The stereoselectivity in the nucleophilic epoxidation of
g-hydroxy-a,b-unsaturated esters has been studied. The
resulting syn/anti a,b-epoxyesters have been converted
into trisubstituted a-phenylsulfanyl g-butyrolactones using
thiophenol. The syn,syn-lactones isomerize easily in basic
media into the syn,anti structures. In order to explain this
interconversion, a retroaldol–aldol sequence has been pro-
posed and a sulfur–oxygen interaction has been invoked to
explain the syn stereochemical preference of the a-sulfured
aldols resulting from the intramolecular aldol reaction.
O
O
5c
4c
60%
40%
Scheme 7. Basic isomerization of lactone 4c: (a) Et3N, THF, 25 ꢁC, 13 h.
The most plausible mechanism for the isomerization is a
retroaldol–aldol sequence (Scheme 8). The retroaldol reac-
tion of 4 is forced by the steric hindrance of the substituents
into syn,syn relationship into the cyclic structure, then
the resulting enolate–aldehyde intermediate gives an aldol
cyclization to furnish a thermodynamic mixture of lactones.
The major product is the more thermodynamically stable
one, 5, having substituents in syn,anti relationship.
5. Experimental section
5.1. General experimental methods
SPh
SPh
SPh
HO
R
O
retroaldol
aldol
HO
R
All solvents used in reactions were freshly distilled from
O
O
+ base
1
O
appropriate drying agents before use. H NMR spectra and
O
O
R
O
13C NMR spectra were measured in CDCl3 (1H, 7.24 ppm;
13C 77.0 ppm) solution at 30 ꢁC on a 300 MHz Mercury
Varian or a 500 MHz Innova Varian NMR spectrometer at
4
5
Scheme 8. Retroaldol–aldol sequence.
´
ꢀ
the Serveis Centrals d’Instrumentacio Cientıfica de la Uni-
versitat Jaume I. Mass spectra were measured in a QTOF I
(quadrupole–hexapole-TOF) mass spectrometer with an
orthogonal Z-spray-electrospray interface (Micromass,
Manchester, UK). IR spectra were recorded as oily films
on NaCl plates on a Perkin–Elmer 2000 FTIR spectrometer.
EM Science Silica Gel 60 was used for column chromato-
graphy while TLC was performed with E. Merck precoated
plates (Kieselgel 60, F254, 0.25 mm). Unless otherwise spec-
ified, all reactions were carried out under argon atmosphere
with magnetic stirring.
A retroaldol–aldol sequence has been invoked by some
authors to explain the isomerization of b-hydroxy a-sulfenyl
carbonylic compounds.16 The two examples shown in
Scheme 9 are taken from the literature16a,b and both repre-
sent isomerizations of anti b-hydroxy a-sulfenyl cyclic
ketones into the syn ones.
O
O
SR
Me
Me
OH
Me
NaSR
SR
Me
OH
O
anti
O
syn
5.1.1. General experimental procedure for the syntheses
of esters 1. To a liquid N2/acetone cold solution of ethyl (E)-
4-oxo-2-butenoate (65.1 mmol) in THF (150 mL) was added
alkyl magnesium chloride solution (26 mL, 78.1 mmol)
drop wise under N2 atmosphere for a period of 5 min. The
resulting mixture was left to warm up to room temperature
for 1 h and then quenched with satd aq NH4Cl solution
and extracted with Et2O (3ꢂ40 mL), the organic layers
were washed (brine), dried (Na2SO4), and concentrated.
The crude oil was purified through chromatography
(silica-gel, hexanes/EtOAc (8:2) and (7:3)) to afford an oil.
R=Et 20%
R=Ph 7%
80%
90%
O
O
SR
Me
Me
OH
Me
SR
Me
OH
base
O
anti
O
syn
Scheme 9. Isomerization of b-hydroxy a-sulfenyl carbonylic compounds.

´
S. Rodrıguez et al. / Tetrahedron 62 (2006) 11112–11123
11118
1
Spectroscopic data for 1a (yield¼29%): H NMR (CDCl3)
d 7.32–7.24 (6H, m), 6.98 (1H, dd, J¼15.5, 5.5 Hz), 6.09
(1H, dd, J¼15.5, 1.5 Hz), 5.30 (1H, m), 4.13 (2H, q,
J¼7.5 Hz), 2.00 (1H, br s), 1.21 (3H, t, J¼7.5 Hz). 13C
NMR (CDCl3) d 166.52, 148.37, 141.02, 128.93, 128.46,
126.63, 120.49, 73.68, 60.55, 14.26 ppm. IR (NaCl)
n 3467, 3064, 3032, 2983, 2937, 2905, 1779, 1717, 1656,
calcd for C12H20O3Na [M+Na+]: 235.1310, found:
235.1302.
1
Spectroscopic data for 1g (yield¼31%): H NMR (CDCl3)
d 7.19 (2H, d, J¼8.5 Hz), 6.97 (1H, dd, J¼15.5, 5.0 Hz),
6.82 (2H, d, J¼15.5 Hz), 6.06 (1H, d, J¼15.5 Hz), 5.19
(1H, d, J¼4.5 Hz), 4.12 (2H, q, J¼7.5 Hz), 3.37 (1H, br s),
1.23 (3H, t, J¼7.5 Hz). 13C NMR (CDCl3) d 166.57,
159.60, 148.83, 133.19, 127.98, 120.02, 114.19, 73.04,
60.48, 55.31, 14.18 ppm. IR (NaCl) n 3468, 2982, 2838,
1719, 1655, 1610, 1586, 1513, 1465, 1369, 1304, 1251,
1173, 1095, 1034, 982, 834, 775 cmꢀ1. HRMS m/z calcd
for C13H16O4Na [M+Na+]: 259.0946, found: 259.0954.
1494, 1455, 1369, 1304, 1175, 1097, 1032, 700 cmꢀ1
.
HRMS m/z calcd for C12H14O3Na [M+Na+]: 229.0841,
found: 229.0814.
1
Spectroscopic data for 1b (yield¼72%): H NMR (CDCl3)
d 6.88 (1H, dd, J¼15.8, 4.8 Hz), 5.94 (1H, dd, J¼15.6,
1.7 Hz), 4.39 (1H, m), 4.12 (2H, q, J¼7.1 Hz), 3.03 (1H,
s), 1.26 (3H, d, J¼6.6 Hz), 1.22 (1H, t, J¼7.1 Hz). 13C
NMR (CDCl3) d 166.76, 151.32, 119.34, 66.84, 60.40,
22.48, 14.07 ppm. IR (NaCl) n 3429, 2983, 1722, 1448,
1369, 1307, 1185, 1039, 980, 868 cmꢀ1. HRMS m/z calcd
for C7H12O3 [M+H+]: 145.0865, found: 145.0828; calcd
for C7H11O3Na [M+Na+]: 167.0684, found: 167.0488.
1
Spectroscopic data for 1h (yield¼19%): H NMR (CDCl3)
d 6.98 (1H, dd, J¼16, 5.5 Hz), 6.00 (1H, dd, J¼15.5,
1.5 Hz), 4.15 (2H, q, J¼7.5 Hz), 3.90 (1H, dd, J¼5.5,
1.5 Hz), 1.25 (3H, t, J¼7.5 Hz), 0.9 (9H, s). 13C NMR
(CDCl3) d 166.51, 147.84, 121.78, 78.90, 60.35, 35.46,
25.65, 14.15 ppm. IR (NaCl) n 3497, 2964, 2907, 2873,
1770, 1722, 1655, 1479, 1369, 1280, 1164, 1112, 1038,
871, 774 cmꢀ1. HRMS m/z calcd for C10H19O3 [M+H+]:
187.1334, found: 187.1307.
1
Spectroscopic data for 1c (yield¼45%): H NMR (CDCl3)
d 6.92 (1H, dd, J¼15.8, 5.1 Hz), 6.00 (1H, dd, J¼15.6,
1.7 Hz), 4.17 (2H, q, J¼7.1 Hz), 4.06 (1H, td, J¼5.3,
0.9 Hz), 1.96 (1H, br s), 1.80 (1H, ddd, J¼6.8, 6.6, 5.9 Hz),
1.26 (3H, t, J¼7.1 Hz), 0.92 (3H, d, J¼6.9 Hz), 0.91 (3H,
d, J¼6.9 Hz). 13C NMR (CDCl3) d 166.54, 148.91, 121.13,
75.91, 60.43, 33.65, 18.24, 17.43, 14.21 ppm. IR (NaCl)
n 3483, 2964, 2934, 2876, 1722, 1656, 1467, 1370, 1274,
1179, 1036, 873 cmꢀ1. HRMS m/z calcd for C9H16O3Na
[M+Na+]: 195.0997, found: 195.0976.
5.1.2. General experimental procedure for the epoxida-
tion of esters 1. To a ꢀ78 ꢁC cold THF (3.5 mL) was added
TBHP (3.3 M in toluene18) (2.2 mmol) and then ethyllithium
(0.5 M in benzene/cyclohexane (9:1)19) (1.61 mmol). The re-
sulting mixture was stirred at ꢀ78 ꢁC for 15 min and then
a solution of compound 1 (1.46 mmol) in THF (2 mL) was
added drop wise and then the mixture was left at ꢀ20 ꢁC
(fridge) for 20 h. Then solid Na2SO3 (120 mg) was added
in one portion and stirred for 15 min, then diluted with
satd aq NH4Cl solution and extracted with Et2O
(3ꢂ30 mL), the organic layers were washed (brine), dried
(Na2SO4), and concentrated. The crude oil was purified
through chromatography (silica-gel, hexanes/EtOAc (7:3)
and (6:4)).
1
Spectroscopic data for 1d (yield¼22%): H NMR (CDCl3,
300 MHz) d 6.89 (1H, dd, J¼15.6, 4.8 Hz), 5.97 (1H, dd,
J¼15.6, 1.5 Hz), 4.21 (1H, dq, J¼5.4, 1.8 Hz), 4.14 (2H,
q, J¼6.9 Hz), 2.61 (1H, br s), 1.52 (3H, m), 1.26 (2H, m),
1.24 (3H, t, J¼7.2 Hz), 0.84 (3H, d, J¼6.6 Hz), 0.83 (1H,
d, J¼6.6 Hz). 13C NMR (CDCl3) d 166.71, 150.49,
119.99, 71.24, 60.40, 34.47, 34.19, 27.92, 22.45, 22.36,
14.13 ppm. IR (NaCl) n 3449, 2957, 1720, 1655, 1467,
1369, 1275, 1177 cmꢀ1. HRMS m/z calcd for C11H20O3Na
[M+Na+]: 223.1310, found: 223.1288.
Spectroscopic data for 2a/3a: 1H NMR (CDCl3) d 7.22–7.34
(5H, m, majoritary and minoritary), 4.78 (1H, d, J¼2.5 Hz,
minoritary), 4.58 (1H, d, J¼4.5 Hz, majoritary), 4.14 (2H,
m, majoritary and minoritary), 3.63 (1H, d, J¼2 Hz, minori-
tary), 3.50 (1H, d, J¼2 Hz, majoritary), 3.41 (1H, dd, J¼4.5,
2 Hz, majoritary), 3.35 (1H, t, J¼2.5 Hz, minoritary), 1.23
(3H, t, J¼6.5 Hz, majoritary and minoritary). 13C NMR
(CDCl3) d 168.71 (minoritary), 168.49 (majoritary),
139.42 (majoritary), 139.67 (minoritary), 128.74, 128.70,
128.49, 128.43, 126.47, 126.39, 72.18 (majoritary), 70.40
(minoritary), 61.75 (majoritary), 61.70 (minoritary), 60.88
(majoritary), 60.64 (minoritary), 51.10 (majoritary), 49.81
(minoritary), 13.99 (majoritary and minoritary) ppm. IR
(NaCl) n 3467, 3058, 3024, 2976, 2926, 2853, 1732, 1452,
1
Spectroscopic data for 1e (yield¼44%): H NMR (CDCl3)
d 6.93 (1H, dd, J¼15.5, 5 Hz), 6.02 (1H, dd, J¼15.6,
1.5 Hz), 4.29 (1H, m), 4.20 (2H, q, J¼7.1 Hz), 1.82 (1H,
d, J¼4.2 Hz), 1.59 (2H, m), 1.33 (2H, m), 1.29 (3H, t,
J¼7.2 Hz), 0.9 (3H, t, J¼7.0 Hz). 13C NMR (CDCl3)
d 166.59, 150.21, 120.20, 71.19, 60.45, 36.41, 27.34,
22.56, 14.25, 13.94 ppm. IR (NaCl) n 3449, 2959, 2872,
1721, 1656, 1466, 1369, 1305, 1275, 1179, 1040,
985 cmꢀ1. HRMS m/z calcd for C10H18O3Na [M+Na+]:
209.1154, found: 209.1141.
1372, 1205, 1093, 1066, 1025, 904, 760, 701 cmꢀ1
.
1
Spectroscopic data for 1f (yield¼25%): H NMR (CDCl3)
HRMS m/z calcd for C12H14O4Na [M+Na+]: 245.079,
found: 245.0790.
d 6.94 (1H, dd, J¼16, 5.5 Hz), 6.01 (1H, dd, J¼15.5,
1.5 Hz), 4.19 (1H, q, J¼7 Hz), 4.07 (1H, td, J¼5.5,
1.5 Hz), 1.97 (1H, br s), 1.62–1.81 (6H, m), 1.4 (1H, m),
1.28 (3H, t, J¼7.5 Hz), 0.99–1.33 (4H, m). 13C NMR
(CDCl3) d 166.54, 149.25, 120.95, 75.44, 60.40, 43.58,
36.41, 28.83, 27.98, 26.31, 26.06, 26.01, 14.20 ppm. IR
(NaCl) n 3460, 2925, 2855, 1715, 1658, 1450, 1369, 1276,
1176, 1113, 1039, 985, 893, 869, 733 cmꢀ1. HRMS m/z
Spectroscopic data for 2b/3b: 1H NMR (CDCl3) d 4.21 (2H,
m, majoritary and minoritary), 3.97 (1H, dq, J¼6.4, 3.1 Hz),
3.97 (1H, dq, J¼6.4, 3.1 Hz, minoritary), 3.78 (1H, dq,
J¼6.4, 4.2 Hz, majoritary), 3.48 (1H, d, J¼2.0 Hz, minori-
tary), 3.43 (1H, d, J¼2.0 Hz, majoritary), 3.20 (1H, m,
minoritary), 3.18 (1H, dd, J¼4.2, 2.0 Hz, majoritary), 1.28

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S. Rodrıguez et al. / Tetrahedron 62 (2006) 11112–11123
11119
(3H, d, J¼6.6 Hz, majoritary and minoritary), 1.26 (1H, d,
J¼6.4 Hz, majoritary), 1.25 (1H, d, J¼6.2 Hz, minoritary).
13C NMR (CDCl3) d 168.97 (minoritary), 168.75 (majori-
tary), 65.96 (majoritary), 64.31 (minoritary), 61.65 (majori-
tary and minoritary), 61.49 (majoritary), 61.09 (minoritary),
50.88 (majoritary), 49.73 (minoritary), 19.80 (majoritary),
18.75 (minoritary), 14.00 (majoritary and minoritary) ppm.
IR (NaCl) n 3477, 2983, 2921, 1738, 1656, 1452, 1372,
1285, 1202, 1028, 978, 901, 806, 720 cmꢀ1. HRMS m/z
calcd for C7H12O4Na [M+Na+]: 183.0633, found: 183.0625.
(minoritary), 22.53 (majoritary), 14.05 (majoritary and
minoritary), 13.87 (majoritary and minoritary) ppm. IR
(NaCl) n 3480, 2934, 2860, 1738, 1633, 1468, 1372, 1200,
1031, 959, 906, 809, 748 cmꢀ1. HRMS m/z calcd for
C10H18O4Na [M+Na+]: 225.1103, found: 225.1109; calcd
for C10H18O4K [M+K+]: 241.842, found: 241.0849.
Spectroscopic data for 2f/3f: 1H NMR (CDCl3) d 4.18 (2H,
m, majoritary and minoritary), 3.56 (1H, dd, J¼5.5, 3.0 Hz,
minoritary), 3.46 (1H, d, J¼2.0 Hz, minoritary), 3.39 (1H, d,
J¼2.0 Hz, majoritary), 3.28 (1H, dd, J¼6.5, 4.0 Hz, majori-
tary), 3.21 (1H, dd, J¼4.0, 2.0 Hz, majoritary), 3.19 (1H, dd,
J¼3.0, 2.0 Hz, minoritary), 1.97 (1H, br s), 1.58–1.87 (5H,
m, majoritary and minoritary), 1.50 (1H, m, majoritary and
minoritary), 1.24 (3H, t, J¼7.5 Hz, majoritary and minori-
tary), 0.95–1.22 (5H, m, majoritary and minoritary). 13C
NMR (CDCl3) d 169.10 (minoritary), 168.84 (majoritary),
73.77 (majoritary), 71.90 (minoritary), 61.67 (majoritary),
61.63 (minoritary), 59.43 (majoritary), 59.22 (minoritary),
50.90 (majoritary), 49.78 (minoritary), 42.30 (majoritary),
41.43 (minoritary), 28.77 (minoritary), 28.71 (majoritary),
28.43 (majoritary), 27.78 (minoritary), 26.28 (minoritary),
26.24 (majoritary), 26.08 (minoritary), 25.96 (minoritary),
25.94 (majoritary), 25.84 (majoritary), 14.07 (majoritary
and minoritary), 13.87 (majoritary and minoritary) ppm.
IR (NaCl) n 3484, 2928, 2855, 1737, 1450, 1371, 1282,
1199, 1096, 1030, 906, 735 cmꢀ1. HRMS m/z calcd for
C12H20O4Na [M+Na+]: 251.1259, found: 251.1255; calcd
for C12H20O4K [M+K+]: 267.0999, found: 267.1006.
Spectroscopic data for 2c/3c: 1H NMR (CDCl3) d 4.21 (2H,
m, majoritary and minoritary), 3.63 (1H, dd, J¼5.0, 3.0 Hz,
minoritary), 3.53 (1H, d, J¼1.5 Hz, minoritary), 3.45 (1H, d,
J¼2.0 Hz, majoritary), 3.35 (1H, d, J¼4.0, 6.5 Hz, majori-
tary), 3.26 (1H, dd, J¼4.0, 2.0 Hz, majoritary), 3.24 (1H,
dd, J¼3.0, 2.0 Hz, minoritary), 1.87 (2H, m, majoritary
and minoritary), 1.29 (3H, t, J¼7.0 Hz, majoritary and
minoritary), 1.00 (3H, d, J¼6.5 Hz, majoritary and minori-
tary), 0.98 (3H, d, J¼6.5 Hz, majoritary and minoritary).
13C NMR (CDCl3) d 169.09 (minoritary), 168.89 (majori-
tary), 74.29 (majoritary), 72.31 (minoritary), 61.75 (majori-
tary), 61.69 (minoritary), 59.34 (minoritary), 59.22
(minoritary), 50.81 (majoritary), 49.73 (minoritary), 32.69
(majoritary), 31.61 (minoritary), 18.46 (majoritary), 18.75
(minoritary), 17.92 (majoritary), 17.34 (minoritary), 14.12
(majoritary and minoritary) ppm. IR (NaCl) n 3497, 2964,
2877, 1732, 1468, 1371, 1285, 1244, 1199, 1028,
905 cmꢀ1. HRMS m/z calcd for C9H16O4Na [M+Na+]:
211.0946, found: 211.0926.
Spectroscopic data for 2g/3g: 1H NMR (CDCl3) d 7.33 (2H,
d, J¼9.0 Hz, majoritary), 7.30 (2H, d, J¼8.5 Hz, minori-
tary), 6.90 (2H, d, J¼8.5 Hz, majoritary and minoritary),
4.86 (1H, d, J¼2.5 Hz, minoritary), 4.61 (1H, d, J¼4.0 Hz,
majoritary), 4.20 (2H, m, majoritary and minoritary), 3.68
(1H, d, J¼2 Hz, minoritary), 3.54 (1H, d, J¼1.5 Hz, majori-
tary), 3.45 (1H, dd, J¼4.5, 2 Hz, majoritary), 3.39 (1H, dd,
J¼2.5, 2.0 Hz, minoritary), 2.55 (1H, br s, majoritary),
1.84 (1H, br s, minoritary), 1.27 (3H, t, J¼7.0 Hz, majori-
tary), 1.26 (3H, t, J¼7.0 Hz, minoritary). 13C NMR
(CDCl3) d 168.75 (minoritary), 168.56 (majoritary),
159.83 (minoritary), 159.74 (majoritary), 131.67 (majori-
tary), 130.68 (minoritary), 127.90 (minoritary), 127.81
(majoritary), 114.18 (majoritary and minoritary), 71.79
(majoritary), 70.03 (minoritary), 61.76 (majoritary), 61.72
(minoritary), 60.93 (majoritary), 60.63 (minoritary), 55.30
(majoritary and minoritary), 51.10 (majoritary), 49.82
(minoritary), 14.04 (majoritary and minoritary) ppm. IR
(NaCl) n 3483, 3058, 2985, 2939, 2909, 2839, 1740, 1613,
1586, 1515, 1466, 1444, 1421, 1372, 1304, 1225, 1202,
1178, 1113, 1096, 1069, 1032, 964, 907, 836, 737,
703 cmꢀ1. HRMS m/z calcd for C13H16O5Na [M+Na+]:
275.0895, found: 275.0855; calcd for C13H16O5K [M+K+]:
291.0635, found: 291.0657.
Spectroscopic data for 2d/3d: 1H NMR (CDCl3) d 4.17 (2H,
m, majoritary and minoritary), 3.74 (1H, dq, J¼4.0, 3.5 Hz,
minoritary), 3.53 (1H, dq, J¼4.0, 4.0 Hz, majoritary), 3.46
(1H, d, J¼2.0 Hz, minoritary), 3.42 (1H, d, J¼2.5 Hz,
majoritary), 3.16 (1H, dd, J¼4.0, 2.0 Hz, majoritary), 3.15
(minoritary, signal overlapped with majoritary), 2.11 (1H,
br s), 1.46–1.58 (4H, m, majoritary and minoritary), 1.32
(1H, m, majoritary and minoritary), 1.24 (3H, t, J¼7.0 Hz,
majoritary and minoritary), 0.84 (3H, d, J¼7.0 Hz, majori-
tary and minoritary), 0.83 (3H, d, J¼7.0 Hz, majoritary
and minoritary). 13C NMR (CDCl3) d 169.09 (minoritary),
168.81 (majoritary), 69.93 (majoritary), 68.33 (minoritary),
61.66 (majoritary), 61.64 (minoritary), 60.73 (majoritary),
60.45 (minoritary), 50.89 (majoritary), 49.69 (minoritary),
34.23 (majoritary), 34.10 (minoritary), 32.30 (majoritary),
31.26 (minoritary), 28.01 (minoritary), 27.93 (majoritary),
22.46 (majoritary), 22.34 (minoritary), 14.03 (majoritary
and minoritary) ppm.
Spectroscopic data for 2e/3e: 1H NMR (CDCl3) d 4.21 (2H,
m, majoritary and minoritary), 3.71 (1H, m, minoritary),
3.58 (1H, m, majoritary), 3.49 (1H, d, J¼1.8 Hz, minori-
tary), 3.44 (1H, d, J¼2.0 Hz, majoritary), 3.17 (1H, dd,
J¼4.0, 2.0 Hz, majoritary), 3.17 (minoritary, signal overlap-
ped with majoritary), 1.58 (2H, m), 1.33 (4H, m), 1.27 (3H, t,
J¼7.1 Hz, majoritary and minoritary), 0.88 (1H, t,
J¼7.1 Hz, majoritary and minoritary). 13C NMR (CDCl3)
d 169.04 (minoritary), 168.80 (majoritary), 69.66 (majori-
tary), 67.99 (minoritary), 61.68 (majoritary), 61.65 (minori-
tary), 60.74 (majoritary), 60.45 (minoritary), 50.89
(majoritary), 49.63 (minoritary), 34.14 (majoritary), 33.05
(minoritary), 27.32 (majoritary), 27.20 (minoritary), 22.59
Spectroscopic data for 2h/3h: 1H NMR (CDCl3) d 6.98 (1H,
dd, J¼16, 5.5 Hz), 6.00 (1H, dd, J¼15.5, 1.5 Hz), 4.15 (2H,
q, J¼7.5 Hz), 3.90 (1H, dd, J¼5.5, 1.5 Hz), 1.25 (3H, t,
J¼7.5 Hz), 0.9 (9H, s). 13C NMR (CDCl3) d 166.51,
147.84, 121.78, 78.90, 60.35, 35.46, 25.65, 14.15 ppm. IR
(NaCl) n 3497, 2964, 2907, 2873, 1770, 1722, 1655, 1479,
1369, 1280, 1164, 1112, 1038, 871, 774 cmꢀ1. HRMS m/z
calcd for C10H18O4Na [M+Na+]: 225.1103, found:

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S. Rodrıguez et al. / Tetrahedron 62 (2006) 11112–11123
11120
225.1103; calcd for C10H18O4Na [M+K+]: 241.0842, found:
241.0882.
19.92, 13.61 ppm. IR (NaCl) n 2981, 2976, 2824, 1718,
1659, 1449, 1370, 1299, 1272, 1158, 1099, 1033, 982,
919, 869, 734 cmꢀ1. HRMS m/z calcd for C9H16O4Na
[M+Na+]: 211.0946, found: 211.0919.
5.1.2.1. 4-(tert-Butyl-diphenyl-silanyloxy)-pent-2-enoic
acid ethyl ester 6a. To an ice-bath cold solution of compound
1b (266 mg, 1.85 mmol) in DMF (5 mL) was added imida-
zole (138 mg, 2.03 mmol) and then tert-butyldiphenylsilyl-
chloride (528 mL, 2.03 mmol). The resulting mixture was
stirred at room temperature (21 ꢁC) for 70 h and then was
quenched with brine and extracted with Et2O (3ꢂ30 mL),
the organic layers were washed (brine), dried (Na2SO4),
and concentrated. The crude oil was purified through chroma-
tography (silica-gel, hexanes/EtOAc (9:1) to afford 542 mg
5.1.3. General experimental procedure for the epoxida-
tion of esters 6. To a ꢀ78 ꢁC cold THF (3.5 mL) was added
TBHP (3.3 M in toluene18) (600 mL, 1.97 mmol) and then
ethyllithium (0.5 M in benzene/cyclohexane (9:1))
(2.9 mL, 1.45 mmol), gas evolution was observed. The re-
sulting mixture was stirred at ꢀ78 ꢁC for 15 min and then
a solution of compound 6 (1.31 mmol) in THF (2 mL) was
added drop wise and then the mixture was stirred at the
desired temperature for the desired time (see Table 4).
Then solid Na2SO3 (110 mg) was added in one portion and
stirred for 15 min, then diluted with satd aq NH4Cl solution
and extracted with Et2O (3ꢂ30 mL), the organic layers were
washed (brine), dried (Na2SO4), and concentrated. The
crude oil was purified through chromatography (silica-gel,
hexanes/EtOAc (7:3)) to afford an oil.
1
(77%) of an oil. H NMR (CDCl3) d 7.76 (2H, dd, J¼7.7,
1.3 Hz), 7.71 (2H, dd, J¼8.1, 1.5 Hz), 7.41 (6H, m), 6.99
(1H, dd, J¼15.6, 4.6 Hz), 6.10 (1H, dd, J¼15.6, 1.5 Hz),
4.54 (1H, m), 4.24 (2H, m), 1.32 (3H, t, J¼7.2 Hz), 1.20
(1H, d, J¼6.4 Hz), 1.17 (s, 9H). 13C NMR (CDCl3)
d 166.42, 151.16, 135.66, 135.62, 133.85, 133.29, 129.66,
127.53, 127.50, 119.16, 68.59, 60.02, 26.88, 23.18, 19.10,
14.13 ppm. IR (NaCl) n 3072, 3050, 2960, 2859, 1722,
1428, 1369, 1295, 1157, 1112, 978, 822, 741, 703 cmꢀ1
.
Spectroscopic data for 7a/8a: 1H NMR (CDCl3) d 7.61 (4H,
m), 7.27 (6H, m), 4.11 (2H, m), 3.67 (1H, m), 3.23 (1H, d,
J¼2 Hz), 3.17 (1H, d, J¼5.2 Hz), 3.13 (1H, d, J¼1.5 Hz),
3.06 (1H, dd, J¼4.5, 1.5 Hz), 1.18 (3H, t, J¼7 Hz), 1.08
(3H, d, J¼6.5 Hz), 1.01(1H, d, J¼6.5 Hz), 0.98 (9H, m).
13C NMR (CDCl3) d 169.02, 168.92, 135.90, 135.83,
135.81, 135.32, 134.80, 133.97, 133.77, 133.32, 133.14,
129.82, 129.77, 129.73, 129.56, 127.66, 127.65, 127.60,
68.89, 67.38, 61.94, 61.53, 61.48, 61.30, 50.99, 50.77,
26.91, 26.85, 26.57, 20.55, 19.76, 19.23, 19.18, 18.99,
14.09, 14.07 ppm. IR (NaCl) n 3072, 2960, 2932, 2892,
2858, 1737, 1472, 1428, 1391, 1374, 1305, 1197, 1113,
1029, 998, 822, 740, 702 cmꢀ1. HRMS m/z calcd for
C7H12O4Na [M+Na+]: 421.1811, found: 421.1844.
HRMS m/z calcd for C23H30O3SiNa [M+Na+]: 405.1862,
found: 405.1822.
5.1.2.2. 4-Triisopropylsilanyloxy-pent-2-enoic acid
ethyl ester 6b. To an ice-bath cold solution of compound
1b (582 mg, 4.04 mmol) in DMF (12 mL) was added imid-
azole (358 mg, 5.25 mmol) and then triisopropylsilylchloride
(980 mL, 4.44 mmol). The resulting mixture was stirred at
room temperature (21 ꢁC) for 42 h and then was quenched
with brine and extracted with Et2O (3ꢂ30 mL), the organic
layers were washed (brine), dried (Na2SO4), and concen-
trated. The crude oil was purified through chromatography
(silica-gel, hexanes/EtOAc (9:1)) to afford 1 g (83%) of an
1
oil. H NMR (300 MHz, CDCl3) d 6.88 (1H, dd, J¼15.3,
4.2 Hz), 5.95 (1H, dd, J¼15.3, 1.8 Hz), 4.51 (1H, dq,
J¼6.3, 1.8 Hz), 4.12 (2H, q, J¼6.9 Hz), 1.23 (3H, d, J¼
6.3 Hz), 1.22 (3H, t, J¼6.3 Hz), 1.01 (s, 9H). 13C NMR
(CDCl3) d 166.59, 151.99, 118.92, 67.81, 60.07, 23.84,
17.92, 17.90, 14.13, 12.24 ppm. IR (NaCl) n 2930, 2868,
1723, 1465, 1369, 1294, 1159, 1094, 883 cmꢀ1. HRMS
m/z calcd for C16H32O3SiNa [M+Na+]: 323.2018, found:
323.1956; calcd for C16H33O3Si [M+H+]: 301.2199, found:
301.2172.
Spectroscopic data for 7b/8b: 1H NMR (CDCl3) d 4.20 (2H,
m, majoritary and minoritary), 3.97 (1H, dq, J¼6.5, 4.0 Hz,
minoritary), 3.80 (1H, dq, J¼5.5, 6.5 Hz, majoritary), 3.42
(1H, d, J¼2.0 Hz, minoritary), 3.31 (1H, d, J¼2.0 Hz, ma-
joritary), 3.19 (1H, dd, J¼5.5, 2.0 Hz, majoritary), 3.10
(1H, dd, J¼4.0, 2.0 Hz), 1.27 (3H, t, J¼7.5 Hz, minoritary),
1.26 (3H, t, J¼7.0 Hz, majoritary), 1.23 (3H, d, J¼6.5 Hz,
majoritary), 1.23 (3H, d, J¼6.5 Hz, minoritary), 1.04
(21H, m, majoritary and minoritary). 13C NMR (CDCl3)
d 169.28 (minoritary), 168.97 (majoritary), 68.41 (majori-
tary), 66.07 (minoritary), 62.29 (majoritary), 61.63 (minori-
tary), 61.53 (majoritary), 61.48 (minoritary), 50.79
(majoritary), 50.52 (minoritary), 20.48 (minoritary), 20.33
(majoritary), 17.95, 17.91 (majoritary and minoritary),
14.06 (majoritary and minoritary), 12.29 (majoritary and mi-
noritary) ppm. IR (NaCl) n 2944, 2887, 2860, 1755, 1465,
1373, 1284, 1244, 1196, 1170, 1122, 1099, 1059, 1031,
999, 907, 883, 827, 761, 681 cmꢀ1. HRMS m/z calcd for
C16H32SiO4Na [M+Na+]: 339.1968, found: 339.1966.
5.1.2.3. 4-Methoxymethoxy-pent-2-enoic acid ethyl
ester 6c. To an ice-bath cold solution of compound 1b
(730 mg, 5.1 mmol) in CH2Cl2 (16 mL) were added di-
isopropylethylamine (3.55 ml, 20.4 mmol), chloromethyl
methyl ether (1.55 ml, 20.4 mmol), and then 4-dimethyl-
aminopyridine (464 mg, 3.8 mmol). The resulting mixture
was stirred at room temperature (23 ꢁC) for 20 h and then
was quenched with brine and extracted with CH2Cl2
(3ꢂ30 mL), the organic layers were washed (brine), dried
(Na2SO4), and concentrated. The crude oil was purified
through chromatography (silica-gel, hexanes/EtOAc (8:2)
and (7:3)) to afford 460 mg (48%) of an oil. 1H NMR
(CDCl3) d 6.58 (1H, dd, J¼15.5, 6.0 Hz), 5.72 (1H, dd,
J¼15.5, 1.5 Hz), 4.35 (2H, s), 4.08 (2H, dq, J¼7.0,
7.0 Hz), 3.92 (2H, q, J¼7.5 Hz), 3.08 (s, 3H), 1.03 (3H, d,
J¼6.5 Hz), 1.01 (3H, t, J¼7.0 Hz). 13C NMR (CDCl3)
d 165.45, 148.31, 120.36, 93.91, 70.49, 59.63, 54.56,
Spectroscopic data for 7c/8c: 1H NMR (CDCl3) d 4.64 (1H,
d, J¼7.0 Hz, minoritary), 4.55 (1H, d, J¼7.0 Hz, minori-
tary), 4.54 (1H, d, J¼7.0 Hz, majoritary), 4.51 (1H, d,
J¼7.0 Hz, majoritary), 4.12 (2H, m, majoritary and minori-
tary), 3.55 (1H, dq, J¼6.5, 5.0 Hz, majoritary), 3.54 (1H, dq,
J¼6.5, 6.0 Hz, majoritary), 3.33 (1H, d, J¼2.0 Hz, majori-
tary), 3.26 (3H, s, minoritary), 3.23 (3H, s), 3.22 (1H, d,

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S. Rodrıguez et al. / Tetrahedron 62 (2006) 11112–11123
11121
J¼2.0 Hz, minoritary), 3.13 (1H, dd, J¼6.0, 2.0 Hz, minori-
tary), 3.05 (1H, dd, J¼5.0, 2.0 Hz, majoritary), 1.19 (3H, t,
J¼6.5 Hz, majoritary and minoritary), 1.16 (3H, d,
J¼6.5 Hz, majoritary and minoritary). 13C NMR (CDCl3)
d 168.77 (majoritary), 168.66 (minoritary), 95.61 (majori-
tary), 95.07 (minoritary), 71.67 (minoritary), 71.14 (majori-
tary), 61.65 (minoritary), 61.53 (majoritary), 60.57
(minoritary), 59.96 (majoritary), 55.43 (majoritary), 55.30
(minoritary), 51.44 (majoritary), 50.14 (minoritary), 17.75
(majoritary), 17.04 (minoritary), 14.04 (majoritary), 14.02
(minoritary) ppm. HRMS m/z calcd for C9H16O5Na
[M+Na+]: 227.0895, found: 227.0874.
J¼6.6 Hz). 13C NMR (CDCl3) d 172.94, 133.21, 132.26,
129.53, 129.50, 128.87, 78.66, 74.74, 53.02, 13.68 ppm.
IR (NaCl) n 3399, 2922, 2853, 1759, 1721, 1623, 1439,
1313, 1259, 1113, 1052 cmꢀ1. HRMS m/z calcd for
C11H12O3SNa [M+Na+]: 247.0405, found: 247.0412.
1
Spectroscopic data for 4c: H NMR (CDCl3) d 7.52–7.54
(2H, m), 7.33–7.36 (3H, m), 4.31 (1H, m), 4.24 (1H, d, J¼
4.0 Hz), 3.86 (1H, dd, J¼10.0, 2.5 Hz), 2.75 (1H, s), 2.27
(1H, m), 1.11 (3H, d, J¼7.0 Hz), 0.99 (3H, d, J¼6.5 Hz).
13C NMR (CDCl3) d 172.21, 132.37, 132.00, 129.68,
128.67, 88.34, 68.55, 57.64, 27.64, 19.83, 17.51 ppm. IR
(NaCl) n 3423, 2965, 1760, 1471, 1440, 1392, 1339, 1171,
1072, 1026, 873, 778, 745, 690 cmꢀ1. HRMS m/z calcd
for C13H16O3SNa [M+Na+]: 275.0718, found: 275.0761
(recrystallized from hexanes/EtOAc, mp 147.8–148.5 ꢁC).
5.1.4. General experimental procedure for the treatment
of 2 with sodium thiophenolate to furnish 4/5. An ice-bath
cold suspension of sodium hydride (60% in mineral oil)
(1.12 mmol) in THF (1 mL) was treated with thiophenol
(2.25 mmol). The mixture was stirred at room temperature
for 15 min and then a solution of the epoxyester 2
(0.75 mmol) in THF (1 mL) was added drop wise and the
mixture was stirred at room temperature for the required
time (see Table 5). Then brine was added and extracted
with Et2O (3ꢂ20 mL), the organic layers were washed
(brine), dried (Na2SO4), and concentrated. The crude oil
was purified through chromatography (silica-gel, hexanes/
EtOAc (7:3) and (6:4)).
1
Spectroscopic data for 5c: H NMR (CDCl3) d 7.52–7.54
(2H, m), 7.33–7.36 (3H, m), 4.35 (1H, m), 4.06 (1H, dd,
J¼10.0, 3.0 Hz), 3.80 (1H, s), 2.42 (1H, d, J¼5.0 Hz),
2.15 (1H, m), 1.10 (3H, d, J¼6.5 Hz), 0.95 (3H, d,
J¼7.0 Hz). 13C NMR (CDCl3) d 173.51, 132.83, 131.58,
129.49, 128.76, 88.43, 73.96, 53.50, 27.01, 19.86,
17.62 ppm. IR (NaCl) n 3449, 3060, 2965, 2876, 1759,
1583, 1471, 1440, 1391, 1370, 1340, 1199, 1173, 1121,
1070, 1024, 955, 916, 821, 778, 747, 690 cmꢀ1. HRMS
m/z calcd for C13H16O3SNa [M+Na+]: 275.0718, found:
275.0721.
Spectroscopic data for 4a: 1H NMR (CDCl3) d 7.50–7.53 (m,
2H), 7.35–7.45 (8H, m), 5.47 (1H, d, J¼3.0 Hz), 4.56 (1H,
ddd, J¼4.0, 3.0, 2.0 Hz), 4.35 (1H, d, J¼4.0 Hz), 2.37
(1H, d, J¼2.0 Hz). 13C NMR (CDCl3) d 172.63, 133.04,
132.59, 129.57, 129.05, 128.71, 128.59, 126.52, 82.98,
71.38, 56.64 ppm. IR (NaCl) n 3460, 3060, 2916, 1951,
1886, 1752, 1581, 1498, 1456, 1438, 1326, 1290, 1214,
Spectroscopic data for 4e: 1H NMR (CDCl3) d 7.45–7.49 (m,
2H), 7.27–7.30 (3H, m), 4.26 (1H, m), 4.20 (1H, m), 4.18
(1H, d, J¼4.0 Hz), 2.70 (1H, s), 1.73–1.90 (2H, m), 1.29–
1.39 (4H, m), 0.86 (3H, t, J¼7.5 Hz). 13C NMR (CDCl3)
d 172.17, 132.38, 132.06, 129.67, 128.67, 82.70, 69.20,
57.24, 28.27, 27.39, 22.54, 13.91 ppm. IR (NaCl) n 3449,
3060, 2958, 2872, 1759, 1583, 1467, 1440, 1307, 1177,
1089, 1024, 938, 832, 745, 691 cmꢀ1. HRMS m/z calcd for
C14H18O3SNa [M+Na+]: 289.0874, found: 289.0856.
1179, 1110, 1024, 994, 954, 942, 815, 790, 701, 634 cmꢀ1
.
HRMS m/z calcd for C16H14O3SNa [M+Na+]: 309.0562,
found: 309.0580 (recrystallized from hexanes/EtOAc, mp
151.5–154.5 ꢁC).
1
Spectroscopic data for 5a: 1H NMR (CDCl3) d 7.48–7.50 (m,
2H), 7.24–7.35 (8H, m), 5.49 (1H, d, J¼4.0 Hz), 4.38 (1H,
dd, J¼4.0, 1.0 Hz), 3.89 (1H, d, J¼1.0 Hz), 2.20 (1H, s).
13C NMR (CDCl3) d 173.05, 132.93, 132.54, 131.21,
129.53, 129.12, 128.98, 128.89, 126.31, 83.27, 75.49,
52.17 ppm. IR (NaCl) n 3389, 3053, 2987, 1776, 1440,
1265, 1156, 1070, 1023, 909, 650 cmꢀ1. HRMS m/z calcd
for C16H14O3SNa [M+Na+]: 309.0562, found: 309.0562
(recrystallized from hexanes/EtOAc, mp 142.5–144.3 ꢁC).
Spectroscopic data for 5e: H NMR (CDCl3) d 7.44–7.45
(2H, m), 7.24–7.35 (3H, m), 4.35 (1H, m), 4.23 (1H, m),
3.89 (1H, d, J¼1.0 Hz), 2.90 (1H, s), 1.59–1.85 (2H, m),
1.22–1.40 (4H, m), 0.83 (3H, t, J¼7.0 Hz). 13C NMR
(CDCl3) d 173.72, 132.83, 131.58, 129.49, 128.76, 83.22,
74.20, 52.87, 27.70, 27.52, 22.42, 13.84 ppm. IR (NaCl)
n 3441, 3059, 2959, 2921, 2859, 1748, 1583, 1479, 1439,
1343, 1274, 1187, 1123, 996, 945, 739, 690 cmꢀ1. HRMS
m/z calcd for C14H18O3SNa [M+Na+]: 289.0874, found:
289.0848.
1
Spectroscopic data for 4b: H NMR (CDCl3) d 7.33–7.57
(m, 5H), 4.51 (1H, dq, J¼6.5, 3 Hz), 4.24 (2H, m), 2.75
1
Spectroscopic data for 4f: H NMR (CDCl3) d 7.45–7.47
1
(1H, s), 1.50 (3H, d, J¼6.0 Hz). H NMR (C6D6) d 7.19
(2H, m), 7.27–7.30 (3H, m), 4.23 (1H, m), 4.16 (1H, d, J¼
4.5 Hz), 3.88 (1H, dd, J¼10.5, 2.5 Hz), 2.70 (1H, s), 0.83–
2.03 (11H, m). 13C NMR (CDCl3) d 172.16, 132.43,
131.97, 129.68, 128.69, 87.10, 68.33, 57.47, 36.58, 30.16,
27.62, 26.32, 25.35, 25.27 ppm. IR (NaCl) n 3470, 3055,
2910, 2854, 1751, 1439, 1265, 1173, 1097, 1001, 944,
895, 704 cmꢀ1. HRMS m/z calcd for C16H20O3SNa
[M+Na+]: 315.1031, found: 315.1040.
(2H, dd, J¼6, 3.5 Hz), 6.90 (3H, t, J¼6 Hz), 3.50 (1H, dq,
J¼6.5, 3 Hz), 3.41 (1H, d, J¼5 Hz), 3.24 (1H, m), 2.11 (1H,
d, J¼2.5 Hz), 1.09 (3H, d, J¼6.5 Hz). 13C NMR (CDCl3)
d 172.94, 132.41, 129.68, 128.71, 78.99, 69.86, 57.31,
14.13 ppm. IR (NaCl) n 3381, 2921, 2860, 1752, 1630,
1436, 1174, 1113 cmꢀ1. HRMS m/z calcd for C11H12O3SNa
[M+Na+]: 247.0405, found: 247.0376.
1
Spectroscopic data for 5b: H NMR (CDCl3) d 7.33–7.57
(m, 5H), 4.65 (1H, dq, J¼6.6, 4.4 Hz), 4.31 (1H, dd,
Spectroscopic data for 5f (partially contaminated with 4f):
1H NMR (CDCl3) d 7.46–7.50 (2H, m), 7.28–7.30 (3H,
m), 4.30 (1H, m), 4.06 (1H, dd, J¼10.5, 3.5 Hz), 3.72 (1H,
J¼4.4, 2.8 Hz), 3.81 (1H, d, J¼2.8 Hz), 1.40 (3H, d,

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S. Rodrıguez et al. / Tetrahedron 62 (2006) 11112–11123
11122
s), 0.85–2.00 (12H, m). 13C NMR (CDCl3) d 172.16, 132.92,
131.59, 129.52, 128.81, 86.85, 73.86, 53.29, 36.08, 30.08,
27.82, 26.23, 25.37, 25.28 ppm. IR (NaCl) n 3443, 3060,
2923, 2854, 1750, 1650, 1439, 1261, 1224, 1189, 1097,
1017, 735, 687 cmꢀ1. HRMS m/z calcd for C16H20O3SNa
[M+Na+]: 315.1031, found: 315.1026.
5.1.6. Experimental procedure for the reduction of 14. An
ice-bath cold solution of compound 14 (48 mg, 0.30 mmol)
in Et2O (4 mL) was treated with zinc borohydride solution20
(0.17 M in Et2O) (18 ml, 3 mmol). The mixture was stirred
cold with an ice-bath for 30 min. Then satd aq NH4Cl
solution was added and extracted with Et2O (3ꢂ20 mL),
the organic layers were washed (brine), dried (Na2SO4),
and concentrated. The crude oil was purified through chro-
matography (silica-gel, hexanes/EtOAc (7:3) and (6:4)) to
afford 36 mg (75%) of an oil.
5.1.5. General experimental procedure for the cyclization
of 9/10 into carbonates 12/13. An ice-bath cold solution of
diols 9/10 (0.44 mmol) in THF (11 mL) was treated with
pyridine (0.22 mmol) and triphosgene (0.48 mmol). The
mixture was refluxed for 7.5 h. Then brine was added and
extracted with Et2O (3ꢂ20 mL), the organic layers were
washed (brine), dried (Na2SO4), and concentrated. The
crude oil was purified through chromatography (silica-gel,
hexanes/EtOAc (8:2) and (7:3)).
Acknowledgements
ꢀ
This work was financed by Conselleria d’Educacio, Cultura i
Ciencia de la Generalitat Valenciana (GV05/071) and Ban-
ꢁ
caixa-UJI foundation (P1 1A2005-14). We thank Serveis
´
ꢀ
Centrals d’Instrumentacio Cientıfica de la Universitat Jaume
I for technical support and especially Prof. William R. Roush
for helpful discussions.
1
Spectroscopic data for 12a: H NMR (CDCl3) d 7.13–7.50
(10H, m), 5.60 (1H, d, J¼4.5 Hz), 4.87 (1H, dd, J¼8.0,
4.5 Hz), 4.11 (2H, m), 3.81 (1H, d, J¼7.5 Hz), 1.16 (1H, t,
J¼7.5 Hz). IR (NaCl) n 3064, 2983, 1815, 1735, 1593,
1458, 1440, 1368, 1312, 1267, 1158, 1069, 1020, 952,
863, 765, 737 cmꢀ1. HRMS m/z calcd for C19H18O5SNa
[M+Na+]: 381.0773, found: 381.0758.
References and notes
1. (a) Chong, J. M.; Sharpless, K. B. Tetrahedron Lett. 1985, 26,
4683–4686; (b) Otsubo, K.; Inanaga, J.; Yamaguchi, M.
Tetrahedron Lett. 1987, 28, 4435–4436; (c) Saito, S.;
Takahashi, N.; Ishikawa, T.; Moriwake, T. Tetrahedron Lett.
1991, 32, 667–670; (d) Lanier, M.; Pastor, R. Tetrahedron
Lett. 1995, 36, 2491–2492; (e) Righi, G.; Rumboldt, G.
1
Spectroscopic data for 13a: H NMR (CDCl3) d 7.06–7.38
(10H, m), 5.86 (1H, d, J¼7.0 Hz), 5.22 (1H, dd, J¼10.5,
7.0 Hz), 4.11 (2H, m), 3.31 (1H, d, J¼10.5 Hz), 1.16 (1H,
t, J¼7.5 Hz). IR (NaCl) n 3063, 2982, 1810, 1728, 1594,
1475, 1441, 1369, 1264, 1157, 1020, 952, 862, 752,
698 cmꢀ1. HRMS m/z calcd for C19H18O5SNa [M+Na+]:
381.0773, found: 381.0765.
ꢀ
J. Org. Chem. 1996, 61, 3557–3560; (f) Concellon, J. M.;
Bardales, E. Org. Lett. 2002, 4, 189–191; (g) Tosaki, S.;
Nemoto, T.; Ohshima, T.; Shibasaki, M. Org. Lett. 2003, 5,
ꢀ
495–498; (h) Concellon, J. M.; Bardales, E.; Llavona, R.
J. Org. Chem. 2003, 68, 1585–1588.
Spectroscopic data for 12b/13b: 1H NMR (CDCl3) d 7.19–
7.49 (5H, m, 12b and 13b), 4.83 (1H, dq, J¼7.0, 6.5 Hz,
13b), 4.73 (1H, dq, J¼6.5, 4.5 Hz, 12b), 4.53 (1H, d,
J¼8.0, 4.5 Hz, 12b), 4.45 (1H, d, J¼10.5, 7.0 Hz, 13b),
4.14 (2H, m, 12b and 13b), 3.70 (1H, d, J¼8.0 Hz, 12b),
3.63 (1H, d, J¼10.5 Hz, 13b), 1.52 (3H, d, J¼6.5 Hz,
12b), 1.31 (3H, d, J¼6.5 Hz, 13b), 1.19 (1H, t, J¼7.0 Hz,
12b), 1.18 (1H, t, J¼7.0 Hz, 13b). IR (NaCl) n 3060,
2955, 2854, 1805, 1732, 1466, 1377, 1259, 1157, 1069,
746, 685 cmꢀ1. HRMS m/z calcd for C14H16O5SNa
[M+Na+]: 319.0616, found: 319.0582.
2. (a) Meth-Cohn, O.; Moore, C.; Taljaard, H. C. J. Chem. Soc.,
Perkin Trans. 1 1988, 2663–2674; (b) Yang, N. C.; Finnegan,
R. B. J. Am. Chem. Soc. 1958, 5, 5845–5848.
´
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3. Rodrıguez, S.; Vidal, A.; Monroig, J. J.; Gonzalez, F. V.
Tetrahedron Lett. 2004, 45, 5359–5361.
4. (a) Niwa, M.; Iguchi, M.; Yamamura, S. Tetrahedron Lett.
1975, 1539–1542; (b) Niwa, M.; Iguchi, M.; Yamamura, S.
Chem. Lett. 1975, 655–658; (c) Niwa, M.; Iguchi, M.;
Yamamura, S. Tetrahedron Lett. 1975, 4395–4398; (d) Niwa,
M.; Iguchi, M.; Yamamura, S. Chem. Lett. 1975, 581–582;
(e) Takeda, K.; Sakurawi, K.; Ishii, H. Tetrahedron 1972, 28,
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3757–3766; (f) Martınez, J. C. V.; Yoshida, M.; Gottlieb,
O. R. Tetrahedron Lett. 1979, 1021–1024.
5.1.5.1. 3-Acetyl-oxirane-2-carboxylic acid ethyl ester
14. An ice-bath cold solution of compound 1b (163 mg,
1.02 mmol) in CH2Cl2 (4 mL) was treated with pyridine
(463 mL, 5.72 mmol) and Dess–Martin periodinane
(574 mg, 1.53 mmol). The mixture was stirred at room tem-
perature (21 ꢁC) for 1.5 h. Then satd aq NaHCO3/Na2S2O3
solution was added, diluted with Et2O, then extracted with
Et2O (3ꢂ20 mL), the organic layers were washed (brine),
dried (Na2SO4), and concentrated. The crude oil was puri-
fied through chromatography (silica-gel, hexanes/EtOAc
(8:2) and (7:3)) to afford 113 mg (70%) of an oil. 1H NMR
(CDCl3) d 4.27 (2H, m), 3.63 (1H, d, J¼2.0 Hz), 3.59 (1H,
d, J¼2.0 Hz), 2.12 (3H, s), 1.32 (3H, t, J¼7.0 Hz). 13C
NMR (CDCl3) d 202.56, 166.71, 62.38, 57.86, 51.83,
24.49, 14.07 ppm. IR (NaCl) n 2983, 2915, 1745, 1718,
5. For stereoselective Michael reactions of g-alkoxy a,b-unsa-
turated esters see: (a) Asao, N.; Shimada, T.; Sudo, T.;
Tsukada, N.; Yazawa, K.; Gyoung, Y. S.; Uyehara, T.;
Yamamoto, Y. J. Org. Chem. 1997, 62, 6274–6282; (b)
Yamamoto, Y.; Chounan, Y.; Nishii, S.; Ibuka, T.; Kitahara,
H. J. Am. Chem. Soc. 1992, 114, 7652–7660; For examples
of asymmetric epoxidation of g-hydroxy-a,b-unsaturated sulf-
ꢀ
oxides and sulfones: (a) Fernandez de la Pradilla, R.; Buergo,
M. V.; Manzano, P.; Montero, C.; Priego, J.; Viso, A.; Cano,
´
ꢀ
F. H.; Martınez-Alcazar, M. P. J. Org. Chem. 2003, 61, 4797–
4805; (b) Jackson, R. F. W.; Standen, S. P.; Clegg, W.;
McCamley, A. J. Chem. Soc., Perkin Trans. 1 1995, 149–156;
(c) Jackson, R. F. W.; Standen, S. P.; Clegg, W. J. Chem.
Soc., Perkin Trans. 1 1995, 141–148.
1459, 1365, 1310, 1202, 1095, 1030, 874, 806 cmꢀ1
.
HRMS m/z calcd for C7H10O4Na [M+Na+]: 181.0477,
found: 181.0462.
6. For synthesis of g-hydroxy-a,b-unsaturated esters from chiral al-
dehydes see: (a) Ref. 5; (b) Marcus, J.; Van Meurs, P. J.; Van den

´
S. Rodrıguez et al. / Tetrahedron 62 (2006) 11112–11123
11123
Nieuwendijk, M. C. H.; Porchet, M.; Brussee, J.; Van der Gen, A.
Tetrahedron 2000, 56, 2491–2495; (c) Pedersen, T. M.; Hansen,
E. L.; Kane, J.; Rein, T.; Helquist, P.; Nourby, P.-O.; Tanner, D.
J. Am. Chem. Soc. 2001, 123, 9738–9742; For synthesis of
g-hydroxy-a,b-unsaturated esters through SPARC reactions
and then enzymatic resolution see: Burgess, K.; Cassidy, J.;
Henderson, I. J. Org. Chem. 1991, 56, 2050–2058.
7. (a) Enders, D.; Zhu, J.; Raabe, G. Angew. Chem., Int. Ed. 1996,
35, 1725–1727; (b) Yamamoto, K.; Yamamoto, N. Chem. Lett.
1989, 1149–1152.
8. Jacques, O.; Richards, S. J.; Jackson, R. F. W. Chem. Commun.
2001, 2712–2713.
9. Tanaka, S.; Yamamoto, H.; Nozaki, H.; Sharpless, K. B.;
Michaelson, R. C.; Cutting, J. D. J. Am. Chem. Soc. 1974, 96,
5254–5255.
15. Fuji, K.; Ichikawa, K.; Node, M.; Fujita, E. J. Org. Chem. 1979,
44, 1661–1664.
16. For cyclic ketones: (a) Silverman, R. B. J. Org. Chem. 1981,
46, 4789–4791; (b) Caine, D.; Crews, E.; Salvino, J. M. Tetra-
hedron Lett. 1983, 24, 2083–2086; For esters: (c) Joven, C.;
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Lemaıtre, S.; Lequex, T.; Pommelet, J. C. Tetrahedron 1998,
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17. (a) Markham, G. D.; Bock, C. W. J. Mol. Struct. 1997, 418,
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Nicolson, I. S.; Parkin, A.; Parsons, S. Acta Crystallogr. 2001,
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C57, 1174–1176; (c) Parkanyi, L.; Kalman, A.; Kucsman, A.;
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Kucsman, A.; Csizmadia, I. G. J. Am. Chem. Soc. 1987, 109,
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10. Garcıa-Ruano, J. L.; Fajardo, C.; Fraile, A.; Martı, M. R.
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11. Behrens, C. H.; Sharpless, K. B. J. Org. Chem. 1985, 50, 5696–
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12. The crystal structures have been deposited at the Cambridge
Crystallographic Data Centre and allocated the deposition
numbers: CCDC 603611 for 4a, CCDC 293151 for 4b, and
CCDC 293009 for 4c.
2237–2245; (g) Beaulieu, P. L.; Kabo, A.; Garrat, D. Can. J.
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18. Preparation of tert-butyl hydroperoxide solution: Hill, J. G.;
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3607–3608.
19. Purchased from Aldrich.
13. Similar behavior was observed for similar lactones by
€
Bruckner, R., et al. Chem.—Eur. J. 1998, 4, 2342–2352.
14. Oishi, T.; Nakata, T. Acc. Chem. Res. 1984, 17, 338–344.
20. For preparation of zinc borohydride solution see: Gensler,
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