Diastereoselective epoxidation of allylic diols derived from Baylis-Hillman adducts

Article abstract of DOI:10.1055/s-2005-872091

The results of a highly diastereoselective epoxidation of allylic diols derived from Baylis-Hillman adducts are reported. The formation of an intramolecular hydrogen bond seems to be responsible for the high anti diastereoselection obtained in this epoxid

Full text of DOI:10.1055/s-2005-872091

PAPER
2297
Diastereoselective Epoxidation of Allylic Diols Derived from Baylis–Hillman
Adducts
D
iastereoselectiv
i
e
E
pox
c
idation of
A
a
llylic
D
iol
r
do S. Porto,a Mario L. A. A. Vasconcellos,b Elizete Ventura,b Fernando Coelho*a
a
Laboratory of Synthesis of Natural Products and Drugs, Organic Chemistry Department, Chemistry Institute/Unicamp, PO Box 6154,
13084-971 Campinas SP, Brazil
Fax +19(55)37883023; E-mail: coelho@iqm.unicamp.br
b
Departamento de Química, Universidade Federal da Paraíba, João Pessoa, PB, Brazil
Received 2 October 2004; revised 11 March 2005
literature pointed out that Markó et al.5 and latter
Hatakeiyama et al.6 have already reported on the highly
syn-diastereoselective epoxidation of Baylis–Hillman ad-
ducts using both Weitz–Scheffer and titanium-mediated
Abstract: The results of a highly diastereoselective epoxidation of
allylic diols derived from Baylis–Hillman adducts are reported. The
formation of an intramolecular hydrogen bond seems to be respon-
sible for the high anti diastereoselection obtained in this epoxida-
tion reaction. The results are complementary to those obtained in oxidation procedures (Scheme 1). Such methodologies
the direct epoxidation of Baylis–Hillman adducts, in which an ele-
vated syn diastereoselectivity was observed.
have been subsequently applied to the synthesis of the ra-
cemic upper-chain of clerocidin and terpenticin and to the
Key words: Baylis–Hillman reaction, epoxidation, allylic alcohol,
silicon, diastereoselectivity
asymmetric synthesis of (–)-mycestericin E, respective-
ly.5,6
OH
O
OH
O
O
H2O2, NaOH
The use of the Baylis–Hillman reaction has significantly
advanced in the last years, as demonstrated by recent re-
ports in the literature.1,2 This reaction is seen as a valuable
strategy for the preparation of multifunctionalized inter-
mediates, which may then be used as substrates for the ra-
cemic and asymmetric syntheses of natural products and
drugs.3
Recently, others4a–g,4j as well as we4h,i have described a
highly diastereoselective hydrogenation (homogeneous
and heterogeneous) reaction of Baylis–Hillman adducts.
Depending on the reaction conditions used it was possible
to obtain both syn and anti hydrogenated products with
high degrees of diastereoselection. Particularly, in the cas-
es we studied, the hydrogenation of silylated Baylis–Hill-
man adducts gave the corresponding reduced products
with elevated syn diastereoselectivity. Based on the data
obtained from this study it was possible to establish a re-
lationship between the diastereoselectivity and the size of
the silylated protecting group. Apparently, the stereo-
chemical results we have observed were exclusively con-
trolled by steric factors. This strategy was used as the key
step for the diastereoselective total synthesis of ( )-sito-
philate, the aggregation pheromone produced by the male
of the granary weevil Sitophilus granarius (L.).3d
R
R
or Ti(OiPr)4, TBHP
Baylis–Hillman adduct
syn epoxides
Scheme 1 Direct epoxidation of Baylis–Hillman adducts
However, the epoxidation of Baylis–Hillman adducts has
been limited so far to only syn-products. On the other
hand, the literature has several reports concerning the
preparation of anti-epoxides.7 Miyashita et al.,7a stimulat-
ed by Nakata’s work,7b reported highly stereoselective
anti-epoxidation of the 4-methyl-5-silyloxyallyl system
with m-chloroperbenzoic acid (MCPBA). In this work,
the silyl group served not only as protective group but also
as an effective directing group for facial selectivity, since
the approach occurs preferentially on the side opposite to
the bulky silyloxy group.
Stimulated by the observations reported by Miyashita et
al. for silylated homoallylic alcohols, we disclose herein
the results of a study focused on the stereochemical course
of epoxidation reactions of allylic diol derived from Bay-
lis–Hillman adducts. Our intention was to observe the ste-
reochemical bias of this reaction and verify a possible
relationship between the protecting group and diastereo-
selectivity. To achieve these results we employed an array
of allylic diols, which have been prepared directly from
Baylis–Hillman adducts bearing different substitution
patterns. The Baylis–Hillman adducts were prepared us-
ing a method recently described by us.8 The results are
summarized in Table 1.
In the course of our research directed towards the exploi-
tation of the synthetic potentiality of the Baylis–Hillman
adducts,3 we decided to investigate the generality of these
diastereoselective reactions on silylated Baylis–Hillman
adducts, working now with epoxides generated from allyl-
ic diols easily prepared from them. A careful search of the
In order to gain preliminary information, we decided to
use tert-butyldimethylsilyl (TBS) as the protecting group.
Our choice was based on two previous observations. First-
ly, TBS is very easy to manipulate, showing reasonable
SYNTHESIS 2005, No. 14, pp 2297–2306
Advanced online publication: 20.07.2005
DOI: 10.1055/s-2005-872091; Art ID: M07504SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
5

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R. S. Porto et al.
PAPER
Table 1 Baylis–Hillman Reaction with Different Aliphatic and
Table 2 Two-step Sequence for the Preparation of Bisallylic alco-
Aromatic Aldehydes
hols from Baylis–Hillman Adducts
OH
O
Yield (%)a
O
Reaction
Baylis–Hillman Adduct
Silylated
Product
CO2CH3
R
OCH3
R
H
R1 = TBS
DABCO, MeOH
)))
Silylation
Reaction
1, R = C6H5
9
10
11
12
13
14
15
16
60
68
95
58
93
83
88
93
R = alkyl or aryl
Baylis–Hillman
adduct
2, R = 4-OCH3C6H4
3, R = 2-BrC6H4
4, R = 4-BrC6H4
5, R = 2-bromopiperonyl
6, R = C2H5
Entry
RCHO
Baylis–Hillman Yield (%)a,b
Adduct
R
1
2
3
4
5
6
7
8
C6H5
1
2
3
4
5
6
7
8
60
88
95
67
72
70
60
75
7, R = i-C4H9
8, R = C6H13
4-OCH3C6H4
2-BrC6H4
4-BrC6H4
2-bromopiperonyl
C2H5
Silylated Product
R1 = TBS
Allylic
Alcohol
Yield (%)a
DIBAL-H
Reduction 10, R = 4-OCH3C6H4
11, R = 2-BrC6H4
9, R = C6H5
17
18
19
20
21
22
23
24
76
75
82
63
60
73
75
60
12, R = 4-BrC6H4
13, R = 2-bromopiperonyl
14, R = C2H5
15, R = i-C4H9
16, R = C6H13
i-C4H9
C6H13
a The reactions were carried out using an ultrasound bath. The devel-
opment of the reactions was followed by GC.
a All yields refer to isolated and purified products.
b Yields of isolated and purified products.
dichloromethane at room temperature furnished a mixture
of diastereoisomeric epoxides 26a/b in 75% yield (3:1,
determined by GC analysis of the crude reaction product).
chemical stability. Secondly, during a hydrogenation
study we observed that an increase in the size of the sub-
stituents bonded to the silicon atom was not necessarily
related to an increase in the diastereoselectivity.
OH
OTBS
TBAF, THF
R
OH
R
OH
The Baylis–Hillman adducts 1–8 were treated with tert-
butyldimethylchlorosilane in DMF, at room temperature,
to provide the corresponding silylated products 9–16. The
silylated Baylis–Hillman adducts were then reduced with
DIBAL-H in anhydrous dichloromethane at –78 °C to
give, after work up, the allylic diols 17–24 (Scheme 2).
The results of this simple and straightforward two-step se-
quence are summarized in Table 2.
r.t., 2 h, 80%
25, R = Ph
17, R = Ph
a) MCPBA
MCPBA
CH2Cl2, r.t., 75%
CH2Cl2, r.t. 75%
b) TBAF, THF, 2 h
r.t., 80%
OH
OH
OH
OH
+
O
O
OR1
OH
O
a) TBSCl, imidazole,
DMF, r.t.
R2
R
OCH3
R
( )-26b
( )-26a
b) DIBAL-H, CH2Cl2
–78 °C
Scheme 3 Epoxidation reaction of unprotected allylic diols
Baylis–Hillman
adduct
9–16, R = alkyl or aryl
R1 = TBS; R2 = CO2CH3
17–24, R = alkyl or aryl
R1 = TBS; R2 = CH2OH
Most probably, the presence of two hydroxyl groups in the
neighborhood of the double bond contributes to enhance
the diastereoselectivity of this epoxidation. The same ex-
perimental protocol was then repeated with the silylated
allylic alcohol 17 (Scheme 3). We also observed the for-
mation of a mixture of diastereoisomers, but now one of
them was present in a considerable excess (13:1, mea-
sured by GC of the crude mixture). Seeking to determine
the relative stereochemistry of the diastereoisomers, we
tried to separate them by column chromatography, how-
ever, without success.
Scheme 2 Two-step sequence for the preparation of allylic diols
from B-H adducts
Before starting the epoxidation with the protected allylic
alcohols, we evaluated the degree of diastereoselectivity
with unprotected allylic diols. Thus, compound 17 (see
Table 2 and Scheme 3) was treated with TBAF in THF at
room temperature for two hours to give 25 in 80% yield
(Scheme 3). The epoxidation of 25 with MPCBA in
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PAPER
Diastereoselective Epoxidation of Allylic Diols
2299
To solve this problem the mixture of epoxide diols was di- minima on the potential energy surfaces as a function of
rectly transformed into the corresponding acetals. The en- Q1234 torsion angle. If we consider exclusively parameters
riched diastereoisomeric mixture (generated from the of a steric nature, the approximation of the oxidant can oc-
reaction with the silylated alcohol) was treated with cur from the both faces of the double bond of conformer
TBAF in THF at room temperature to provide the epoxide 25a (Figure 1). However, a slight preference for the re
diols in 80% yield, which was treated with 2,2-dimeth- face can occur. On other hand, in conformation 25b
oxypropane in the presence of a catalytic amount of cam- (Figure 1) the si face is more favored for attack than the
phorsulfonic acid (CSA) at room temperature for 24 hours re. Conformation 25b is slightly more stable than 25a
to give 27 in 60% yield (Scheme 4).
(DDH 0.13 kcal/mol). This small energy difference prob-
ably explains the preferential attack on the si face and,
consequently, the preferential formation of the anti dia-
stereoisomer. Additionally, to minimize the allylic strain
A,1,3 the bulky aromatic ring should be positioned prefer-
entially on one face of the double bond, being responsible
for the moderate degree of diastereoselectivity observed.9
At this stage only one of the two diastereoisomeric acetals
was detected. The results obtained from a NOE experi-
ment with this diastereoisomer 27a are depicted in
Scheme 4. To avoid any doubt concerning the results of
the NOE experiment, the same procedure was repeated
with a sample of syn epoxide, which was prepared accord-
ing to the procedure described by Hatakeiyama.6b The
NOE experiment indicates that the relative stereochemis-
try of the major diastereoisomer is anti. These findings are
consistent with those reported in the literature.7a,b
When we compare the spectroscopic data (1H and 13C
NMR and NOE) recorded for the mixture of products ob-
tained in the epoxidation of the unprotected alcohol with
those obtained in the epoxidation of the silylated alcohols
we observe that the major diastereoisomer was identical in
both cases. Hence, the epoxidation of the unprotected al-
cohols furnishes preferentially the anti epoxide.
In order to explain our results we made some calculations.
In Figure 1, the completely optimized geometry obtained
at the AM1 level for the allylic diol 25 is shown (see,
Scheme 3). The conformations 25a and 25b represents the
Figure 1 Minimal energy conformations for allylic diol 25
2,2-DMP,
CSA, 60%
OH
O
O
OH
O
O
O
O
+
+
R
OH
R
OH
R
R
O
O
26a
26b
27b
27a
H
R = Ph
H
Ph
O
O
O
H
H
CH3
CH3
H
2.58%
2.70%
27a
Irradiated
at 5.30 ppm
OH
OH
OH
1.47%
Ref. 6b
CO2CH3
CO2CH3
O
CO2CH3
+
R
R
R
O
R
O
R = OCH3C4H6
H
29
2
H
CH3
28
O
H
H
H
CH3
2.47%
DIBAL-H, –78 °C
CH2Cl2, 2 h, 50%
2.23%
Irradiated
at 5.18 ppm
2,2-DMP,
CSA, 40%
OH
O
O
O
R
OH
R
O
31
31
30
Scheme 4 Acetal preparation and NOE experiment
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2300
R. S. Porto et al.
PAPER
With these data in hand, we carried out epoxidations with
the other silylated allylic diols 18–24 using the same ex-
perimental protocol as described above for 17. The results
are summarized in Table 3. The data obtained in this reac-
tion are very intriguing. A good level of anti diastereose-
lection was observed for all allylic alcohols derived from
aromatic aldehydes, however, some exceptions were no-
ticed. Curiously, the diastereoselectivity observed for the
allylic alcohols prepared from 2-bromobenzaldehyde and
2-bromopiperonal is lower than that observed for allylic
alcohols without substituents on the ortho position (see
Table 3, entries 3 and 5). Moreover, for all allylic alcohols
prepared from aliphatic aldehydes a poor degree of dia-
stereoselectivity was observed (Table 3, entries 6–8).
Figure 2 Minimized conformations for the silylated allylic diol 17
Table 3 Diastereoselectivity in the Epoxidation of the Silylated Al-
lylic Alcohols
for all possible relative low energy conformers like 17b,
the same phenomena have been observed.
Entry
Silylated Allylic Alcohol
Prod- Yield anti:syn
Seeking to evaluate the accuracy of the results that stem
from the calculations, monosilylated allylic diol 21 was
treated with tert-butyldiphenylsilyl chloride and imida-
zole in DMF to provide compound 40, which was submit-
ted to epoxidation with MCPBA, furnishing a mixture of
diastereoisomers 41a/41b (anti:syn = 1:1) (Scheme 5).
Not surprisingly, no diastereoselectivity was observed in
this epoxidation (1H NMR and GC analyses), which con-
firm the calculated results (Scheme 5).
uct
32
33
34
35
36
37
38
39
(%)a
76
75
82
63
60
65
75
60
Ratiob
12: 1
13: 1
3: 1
1
2
3
4
5
6
7
8
17, R = C6H5
18, R = 4-OCH3C6H4
19, R = 2-BrC6H4
20, R = 4-BrC6H4
21, R = 2-bromopiperonyl
22, R = C2H5
10: 1
3: 1
2: 1
OTBS
TBDPSCl, DMAP,
Et3N, CH2Cl2
OTBS
23, R = i-C4H9
1.4: 1
2: 1
R
OTBDPS
R
OH
r.t., 18 h, 80%
24, R = C6H13
40
21, R = 2-Br-Piperonyl
a All yields refer to isolated and purified products.
MCPBA
b Diastereoselectivity was measured by 1H NMR and capillary GC.
The crude products were transformed into the corresponding 1,3-cy-
clic acetals, which were used in an NOE experiment.
CH2Cl2, r.t., 75%
OTBS
OTBS
+
R
OTBDPS
R
OTBDPS
O
O
It seems that different effects are responsible for the dia-
stereoselectivity attained. In order to explain our results,
we calculated the minimal energy conformations (using
AM1 semiempirical calculation) for the silylated diols.
For those allylic alcohols without substituents in the ortho
position (e.g. 17), two possible low energy conformations
17a and 17b were found (Figure 2). Both conformations
have a hydrogen bond between the primary hydroxyl
group and the oxygen atom bonded to silicon atom, which
stabilizes these conformations and contributes to decrease
the total energy. All other possible conformers, in which
this hydrogen bond was not considered, exhibited a much
higher energy level. In Figure 2, we show the minimal en-
ergy conformations for the silylated allylic diol 17. The
energy difference between them is very small (DDH =
–0.11 kcal/mol).
( )-41b
( )-41a
1 : 1
Scheme 5 Epoxidation reaction of the diprotected allylic diol 36
Now we turn our attention to the results obtained with the
allylic diols 19, 21, 22–24. The presence of a substituent
in the ortho position of the aromatic ring (compounds 19
and 21) changes the conformation, because now the aryl
group is turned away from the double bond. As a conse-
quence both faces of the double bond could be attacked,
although a little preference for the si face is maintained
(see Figure 3, A). On the other hand, the replacement of
an aryl group by an alkyl renders both faces of the allylic
diols almost similar. For these cases, the diastereoselec-
tivity is really very poor (see Figure 3, B).
As the major diastereoisomer provided by epoxidation is
that with an anti relative stereochemistry, this method
could be considered as a valuable alternative for the prep-
aration of anti epoxides from Baylis–Hillman adducts. To
demonstrate this, the primary hydroxyl group of allylic
epoxide 35 was oxidized with the oxalyl chloride/Et3N/
The TBS group in conformer 17a is far away from the ep-
oxidation site (double bond), and thus, under these cir-
cumstances the si face is completely free to be attacked by
the oxidizing reagent. However, the re face is blocked by
the presence of the phenyl group. It is worth noting that,
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PAPER
Diastereoselective Epoxidation of Allylic Diols
2301
phosphomolybdic acid and heating. All Baylis–Hillman reactions
were sonicated in an UNIQUE model GA 1000 ultrasonic bath
(1000 W, 25 kHz). Ice was added occasionally to avoid the increase
of the water temperature of the ultrasonic bath, which was main-
tained between 30 and 40 °C. Aromatic and aliphatic aldehydes
were purchased from Aldrich, Acros or Lancaster, and were used
without prior purification.
Baylis–Hillman Adducts; General Procedure
A mixture of the aliphatic or aromatic aldehyde (1 mmol), methyl
acrylate (112 mg, 1.3 mmol) and DABCO (73 mg, 0.65 mmol) in
MeOH was sonicated for 2–3 d. Ultrasound bath temperature was
constantly monitored and kept at 30–40 °C during the reaction by
adding ice or by using a refrigerated circulator. After completion of
the reaction, the mixture was diluted with CH2Cl2 (50 mL). The or-
ganic solution was washed with 10% aq HCl (2 × 20 mL) and brine
(20 mL), and then dried (Na2SO4). After filtration and solvent re-
moval, the residue was filtered through a pad of silica gel to furnish
the corresponding Baylis–Hillman adduct as a viscous oil or a solid
(Table 1).
Figure 3 Minimized conformations for the silylated allylic diols 19
and 22
DMSO (Swern reagent) in dichloromethane and the re-
sulting aldehyde directly transformed to the carboxylic
acid by oxidation with NaClO2, in an overall yield of 50%
(Scheme 6).10
( )-Methyl 2-[Hydroxy(phenyl)methyl]acrylate (1)
Yield: 60%; colorless oil.
IR (film): 3467, 1720 cm–1.
1H NMR (CDCl3, 300 MHz): d = 7.53–7.46 (m, 5 H), 6.23 (s, 1 H),
5.74 (s, 1 H), 5.45 (s, 1 H), 3.60 (s, 3 H), 2.81 (s, 1 H, exchangeable
with D2O).
OTBS
1. (COCl)2, Et3N, DMSO
OTBS
CH2Cl2, 0 °C
CO2H
O
R
OH
R
O
2. NaClO2, NaH2PO4
43
13C NMR (CDCl3, 75.4 MHz): d = 166.4, 141.7, 141.0, 128.2,
35, R = 4-BrC6H4
127.6, 126.4, 125.8, 73.0, 51.9.
Scheme 6 anti-Epoxides from Baylis–Hillman adducts.
( )-Methyl 2-[Hydroxy(4-methoxyphenyl)methyl]acrylate (2)
Yield: 88%; yellow-tinged oil.
IR (film): 3347, 1715 cm–1.
1H NMR (CDCl3, 300 MHz): d = 7.29 (d, 2 H, J = 9 Hz), 6.85 (d, 2
H, J = 9 Hz), 6.32 (s, 1 H), 5.87 (s, 1 H), 5.51 (s, 1 H), 3.79 (s, 3 H),
3.07 (s, 1 H, exchangeable with D2O).
The epoxidation reaction of allylic diols prepared from the
Baylis–Hillman adduct occurs with a high degree of dias-
tereoselectivity. Surprisingly, no influence of the protect-
ing group in this diastereoselection was observed. Based
on the results obtained from theoretical quantum chemis-
try calculations, the diastereoselectivity seems to be con-
trolled by the formation of an intermolecular hydrogen
bond which contributes to minimize the energy of the re-
active conformers.
13C NMR (CDCl3, 75.4 MHz): d = 166.4, 158.9, 141.9, 133.2,
127.7, 125.3, 113.6, 72.5, 55.1, 51.8.
( )-Methyl 2-[2-Bromophenyl(hydroxy)methyl]acrylate (3)
Yield: 95%; yellow-tinged oil.
This sequence allows the stereoselective preparation of
highly functionalized epoxides, which could be used as
starting materials for the synthesis of several classes of
products. As the epoxidation furnished preferentially the
epoxide with an anti relative stereochemistry, this method
could be used as an alternative to those already described
for the preparation of syn epoxides from Baylis–Hillman
adducts and are complementary to them, as demonstrated.
IR (film): 3437, 1718 cm–1.
1H NMR (CDCl3, 300 MHz): d = 7.55 (dd, J = 1.4, 8.0 Hz, 1 H),
7.35 (m, 1 H), 7.17 (m, 1 H), 6.35 (d, J = 0.74 Hz, 1 H), 5.94 (s, 1
H), 5.57 (t, J = 1.1 Hz, 1 H), 3.78 (s, 3 H), 2.95 (s, 1 H, exchange-
able with D2O).
13C NMR (CDCl3, 75.4 MHz): d = 166.7, 140.4, 139.6, 132.6,
129.1, 128.2, 127.5, 126.9, 122.9, 71.4, 52.1.
( )-Methyl 2-[4-Bromophenyl(hydroxy)methyl]acrylate (4)
Yield: 67%; colorless viscous oil.
IR (film): 3425, 1717 cm–1.
1H NMR (CDCl3, 300 MHz): d = 7.46 (d, J = 8 Hz, 2 H), 7.24 (d,
J = 7 Hz, 2 H), 6.33 (br s, 1 H), 5.82 (br s, 1 H), 5.50 (s, 1 H), 3.72
(s, 3 H).
13C NMR (CDCl3, 75.4 MHz): d = 166.3, 141.4, 140.1, 131.3,
128.1, 126.2, 121.6, 72.7, 52.0.
1
The H and 13C spectra were recorded with a Varian Gemini BB
spectrometer at 300 MHz and 75.4 MHz, respectively, or on an In-
ova Instrument at 500 MHz and 125 MHz, respectively. The mass
spectra were recorded using a HP model 5988A GC/MS with a
High-Resolution Autospec/EBE spectrometer. IR spectra were ob-
tained with a Nicolet model Impact 410 spectrometer. Yields and
diastereoselectivities were determined from GC analysis on a
HP6890 with flame ionization detector, using a HP-5 capillary
(cross linked 5% phenyl methyl siloxane, 28 m) column. Experi-
mental manipulations and reactions were not performed under a dry
atmosphere or employing anhyd solvents, unless otherwise speci-
fied. Purifications and separations by column chromatography were
performed on silica gel, using normal or flash chromatography.
TLC visualization was achieved by spraying with 5% ethanolic
( )-Methyl 2-[(6-Bromo-1,3-benzodioxol-5-yl)(hydroxy)meth-
yl]acrylate (5)
Yield: 72%; yellow-tinged viscous oil, which crystallized on stand-
ing; mp 101–102 °C.
Synthesis 2005, No. 14, 2297–2306 © Thieme Stuttgart · New York

2302
R. S. Porto et al.
PAPER
IR (film): 3473, 1716 cm–1.
1H NMR (CDCl3, 300 MHz): d = 7.28 (d, J = 9 Hz, 2 H), 6.85 (d,
J = 9 Hz, 2 H), 6.23 (s, 1 H), 6.07 (s, 1 H), 5.56 (s, 1 H), 3.79 (s, 3
H), 3.67 (s, 3 H), 0.88 (s, 9 H), 0.06 (s, 3 H), –0.01 (s, 3 H).
1H NMR (CDCl3, 300 MHz): d = 7.02 (s, 1 H), 6.99 (s, 1 H), 6.35
(s, 1 H), 5.99 (s, 2 H), 5.86 (s, 1 H), 5.63 (s, 1 H), 3.79 (s, 3 H), 2.84
(s, 1 H, exchangeable with D2O).
13C NMR (CDCl3, 75.4 MHz): d = 166.2, 158.6, 143.8, 134.6,
128.1, 123.2, 113.2, 72.2, 55.1, 51.6, 25.8, 17.5, –4.9.
13C NMR (CDCl3, 75.4 MHz): d = 166.8, 147.8, 147.5, 140.5,
133.0, 126.8, 113.5, 112.5, 108.2, 101.8, 71.4, 52.2.
( )-Methyl 2-[(2-Bromophenyl)(tert-butyldimethylsilyl-
oxy)methyl]acrylate (11)
Yield: 95%; colorless viscous oil.
IR (film): 2930, 1729, 1471 cm–1.
1H NMR (CDCl3, 300 MHz): d = 7.46 (dd, J = 8.1, 13.0 Hz, 1 H),
7.32–7.26 (m, 2 H), 7.09 (t, J = 7.7 Hz, 1 H), 6.27 (s, 1 H), 5.99 (s,
1 H), 5.74 (t, J = 1.3 Hz, 1 H), 3.70 (s, 3 H), 0.84 (s, 9 H), 0.10 (s, 3
H), –0.11 (s, 3 H).
13C NMR (CDCl3, 75.4 MHz): d = 170.9, 146.3, 141.9, 139.0,
133.7, 128.0, 127.6, 125.2, 123.3, 118.6, 72.2, 51.4, 26.0, 18.4,
–4.3, –4.5.
( )-Methyl 2-(1-Hydroxypropyl)acrylate (6)
Yield: 70%; yellow-tinged fluid oil.
IR (film): 3409, 1715 cm–1.
1H NMR (CDCl3, 300 MHz): d = 6.22 (br s, 1 H), 5.78 (br s, 1 H),
4.31 (t, J = 7 Hz, 1 H), 3.75 (s, 3 H), 2.80 (s, 1 H, exchangeable with
D2O), 1.73–1.55 (m, 2 H), 0.90 (t, J = 8 Hz, 3 H).
13C NMR (CDCl3, 75.4 MHz): d = 167.2, 142.3, 125.4, 73.3, 52.2,
29.5, 10.5.
( )-Methyl 2-(1-Hydroxy-4-methylbutyl)acrylate (7)
Yield: 60%; colorless fluid oil.
IR (film): 3470, 1715 cm–1.
( )-Methyl 2-[(4-Bromophenyl)(tert-butyldimethylsilyl-
oxy)methyl]acrylate (12)
1H NMR (CDCl3, 300 MHz): d = 6.18 (s, 1 H), 5.78 (s, 1 H), 4.45
(q, J = 3 Hz, 1 H), 3.75 (s, 3 H), 2.51 (s, 1 H), 1.78 (sept, J = 7 Hz,
1 H), 1.58–1.35 (m, 2 H), 0.93–0.90 (m, 6 H).
13C NMR (CDCl3, 75.4 MHz): d = 166.8, 142.8, 124.4, 69.7, 51.8,
45.4, 24.8, 23.3, 21.8, 20.3.
Yield: 58%; slightly yellow viscous oil.
IR (film): 2933, 1701, 1495 cm–1.
1H NMR (CDCl3, 300 MHz): d = 7.41 (d, J = 8 Hz, 2 H), 7.24 (d,
J = 9 Hz, 2 H), 6.26 (s, 1 H), 6.09 (s, 1 H), 5.55 (s, 1 H), 3.68 (s, 3
H), 0.88 (s, 9 H), 0.06 (s, 3 H), –0.08 (s, 3 H).
13C NMR (CDCl3, 75.4 MHz): d = 166.4, 143.8, 142.1, 131.5,
129.1, 124.4, 121.6, 72.6, 52.2, 26.3, 18.7, –4.2, –4.3.
( )-Methyl 2-(1-Hydroxyheptyl)acrylate (8)
Yield: 75%; colorless fluid oil.
IR (film): 3469, 1719 cm–1.
( )-Methyl 2-[(6-Bromo-1,3-benzodioxol-5-yl)(tert-butyl-
dimethylsilyloxy)methyl]acrylate (13)
Yield: 93%; colorless viscous oil.
IR (film): 2929, 1728, 1501 cm–1.
1H NMR (CDCl3, 300 MHz): d = 6.95 (s, 1 H), 6.89 (s, 1 H), 6.27
(t, J = 2.6 Hz, 1 H), 5.97 (dd, J = 1.5, 9.2 Hz, 2 H), 5.92 (s, 1 H),
5.84 (t, J = 2.9 Hz, 1 H), 3.72 (s, 3 H), 0.87 (s, 9 H), 0.12 (s, 3 H),
–0.05 (s, 3 H).
13C NMR (CDCl3, 75.4 MHz): d = 166.1, 147.5, 147.2, 143.0,
134.6, 124.9, 113.3, 112.1, 108.8, 101.6, 71.4, 51.7, 25.8, 18.1,
–4.5, –4.8.
1H NMR (CDCl3, 300 MHz): d = 6.21 (br s, 1 H), 5.78 (br s, 1 H),
4.38 (t, J = 6 Hz, 1 H), 3.77 (s, 3 H), 2.29 (s, 1 H), 1.65–1.61 (m, 2
H), 1.35–1.28 (m, 8 H), 0.87 (t, J = 7 Hz, 3 H).
13C NMR (CDCl3, 75.4 MHz): d = 167.0, 142.4, 124.9, 71.8, 51.8,
36.1, 31.7, 29.0, 25.7, 22.5, 14.0.
Silylation (TBS Ether) of Baylis–Hillman Adducts; General
Procedure
A mixture of the adduct 1–8 (1 mmol), tert-butyldimethylsilyl chlo-
ride (96 mg, 1.3 mmol) and imidazole (170 mg, 2.5 mmol) in anhyd
DMF (0.5 mL) was stirred at r.t. under N2 for 18 h. After that, the
mixture was quenched with hexane (30 mL). The hexane phase was
washed with brine (2 × 10 mL) and distilled H2O (20 mL), and dried
(Na2SO4). After evaporation of the solvent, the residue was purified
by silica gel column chromatography (eluent: hexane–EtOAc,
90:10).
( )-Methyl 2-(1-tert-Butyldimethylsilyloxypropyl)acrylate (14)
Yield: 65%; colorless fluid oil.
IR (film): 2955, 1730, 1519 cm–1.
1H NMR (CDCl3, 300 MHz): d = 6.23 (s, 1 H), 5.90 (s, 1 H), 4.56
(t, J = 5 Hz, 1 H), 3.74 (s, 3 H), 1.48–1.43 (m, 2 H), 0.90 (s, 9 H),
0.85 (t, J = 5 Hz, 3 H), 0.09 (s, 3 H), –0.01 (s, 3 H).
13C NMR (CDCl3, 75.4 MHz): d = 166.7, 124.5, 71.0, 51.5, 30.3,
25.7, 18.1, 9.0, –5.1.
( )-Methyl 2-[(tert-Butyldimethylsilyloxy)(phenyl)methyl]
acrylate (9)
Yield: 60%; colorless viscous oil.
IR (film): 2955, 1722, 1504 cm–1.
1H NMR (CDCl3, 300 MHz): d = 7.36–7.27 (m, 5 H), 6.21 (s, 1 H),
6.09 (s, 1 H), 5.62 (s, 1 H), 3.68 (s, 3 H), 0.90 (s, 9 H), 0.04 (s, 3 H),
–0.09 (s, 3 H).
( )-Methyl 2-(1-tert-Butyldimethylsilyloxybutyl-3-methyl)acry-
late (15)
Yield: 88%; colorless viscous oil.
13C NMR (CDCl3, 75.4 MHz): d = 166.6, 144.2, 142.8, 128.3,
IR (film): 2929, 1710, 1492 cm–1.
127.6, 127.3, 124.1, 73.1, 52.0, 26.2, 18.6, –4.4.
1H NMR (CDCl3, 300 MHz): d = 6.21 (s, 1 H), 5.91 (s, 1 H), 4.61
(q, J = 3 Hz, 1 H), 3.75 (s, 3 H), 1.77 (sept, J = 7 Hz, 1 H), 1.43–
1.36 (m, 2 H), 0.93–0.82 (m, 6 H), 0.90 (s, 9 H), 0.06 (s, 3 H), –0.03
(s, 3 H).
13C NMR (CDCl3, 75 MHz): d = 166.5, 144.7, 124.0, 68.8, 51.6,
48.1, 25.9, 24.5, 24.0, 21.8, 18.2, –4.3, –4.8.
( )-Methyl 2-[(tert-Butyldimethylsilyloxy)(4-methoxyphe-
nyl)methyl]acrylate (10)
Yield: 68%; colorless viscous oil.
IR (film): 2954, 1722, 1511 cm–1.
Synthesis 2005, No. 14, 2297–2306 © Thieme Stuttgart · New York

PAPER
Diastereoselective Epoxidation of Allylic Diols
2303
( )-Methyl 2-(1-tert-Butyldimethylsilyloxyheptyl)acrylate (16)
Yield: 95%; colorless viscous oil.
IR (film): 2949, 1721, 1509 cm–1.
1H NMR (CDCl3, 300 MHz): d = 6.21 (s, 1 H), 5.90 (s, 1 H), 4.57
(q, J = 3 Hz, 1 H), 3.75 (s, 3 H), 1.63–1.58 (m, 2 H), 1.38–1.20 (m,
8 H), 0.90 (s, 9 H), 0.88 (t, J = 7 Hz, 3 H), 0.06 (s, 3 H), 0.01 (s, 3 H).
1H NMR (CDCl3, 300 MHz): d = 7.45 (d, J = 8 Hz, 2 H), 7.24 (d,
J = 8 Hz, 2 H), 5.28 (s, 1 H), 5.20 (s, 1 H), 5.15 (s, 1 H), 4.09 (d,
J = 14 Hz, 1 H), 3.91 (d, J = 14 Hz, 1 H), 0.90 (s, 9 H), 0.08 (s, 3
H), 0.03 (s, 3 H).
13C NMR (CDCl3, 75.4 MHz): d = 149.8, 141.5, 131.1, 128.2,
127.6, 112.1, 62.9, 29.7, 25.8, 18.3, –4.8, –4.9.
13C NMR (CDCl3, 75 MHz): d = 166.6, 144.0, 124.2, 70.2, 51.6,
37.9, 31.9, 29.3, 25.9, 25.0, 22.7, 18.2, 14.2, –4.5, –4.8.
( )-2-[(6-Bromo-1,3-benzodioxol-5-yl)(tert-butyldimethylsilyl-
oxy)methyl]prop-2-en-1-ol (21)
Yield: 91%; colorless oil.
IR (film): 3350, 2949, 2931, 2863 cm–1.
Reduction of Silylated Baylis–Hillman Adducts; General Proce-
dure
To a solution of silylated Baylis–Hillman adduct 9–16 (6.2 mmol)
in anhyd CH2Cl2 (20 mL) was added slowly at –78 °C under argon,
a solution of DIBAL-H (15 mmol of a 1 mol/L solution in toluene).
The resulting solution was stirred for 2 h. After checking for the
complete consumption of starting material by TLC, an aq sat. solu-
tion of NaOAc was added (50 mL). The resulting solution was
transferred to a beaker containing a mixture of aq sat. solution of
NH4Cl (10 mL) and EtOAc (50 mL). The mixture was stirred for 1
h until the formation of a gel. It was then filtered over a pad of
Celite. The filtrate was dried (Na2SO4) and concentrated under re-
duced pressure. The crude product was purified by silica gel column
chromatography (hexanes–EtOAc, 10%) to provide the correspond-
ing allylic alcohols.
1H NMR (CDCl3, 300 MHz): d = 7.00 (s, 1 H), 6.93 (s, 1 H), 5.99
(s, 1 H), 5.96 (s, 1 H), 5.59 (s, 1 H), 5.17 (d, J = 5 Hz, 2 H), 4.10 (d,
J = 13 Hz, 1 H), 4.03 (J = 13 Hz, 1 H), 1.92 (s, 1 H), 0.98 (s, 9 H),
0.03 (s, 3 H), –0.02 (s, 3 H).
13C NMR (CDCl3, 75.4 MHz): d = 148.8, 147.5, 135.0, 112.4, 111.9,
108.3, 101.6, 74.9, 63.4, 25.8, 18.2, –4.7, –4.9.
( )-2-(1-tert-Butyldimethylsilyloxypropyl)-2-prop-2-en-1-ol
(22)
Yield: 73%; colorless oil.
IR (film): 3378, 2954, 2895, 2828 cm–1.
1H NMR (CDCl3, 300 MHz): d = 5.06 (s, 1 H), 4.99 (s, 1 H), 4.30
(d, J = 12 Hz, 1 H), 4.15 (t, J = 5 Hz, 1 H), 4.10 (d, J = 12 Hz, 1 H),
2.04 (s, 1 H), 1.64–1.56 (m, 2 H), 0.89 (s, 9 H), 0.09 (s, 3 H), 0.08
(t, J = 5 Hz, 3 H), 0.05 (s, 3 H).
13C NMR (CDCl3, 75.4 MHz): d = 149.4, 111.7, 77.8, 63.5, 29.4,
25.62, 18.0, 9.9, –3.6.
( )-2-[(tert-Butyldimethylsilyloxy)(phenyl)methyl]-2-prop-2-
en-1-ol (17)
Yield: 86%; yellow tinged oil.
IR (film): 3377, 2954, 2929, 2856 cm–1.
1H NMR (CDCl3, 300 MHz): d = 7.37–7.24 (m, 5 H), 5.23 (s, 1 H),
5.12 (s, 1 H), 5.08 (s, 1 H), 4.06 (d, J = 12 Hz, 1 H), 3.85 (d, J = 12
Hz, 1 H), 1.91 (s, 1 H), 0.97 (s, 9 H), 0.15 (s, 3 H), –0.01 (s, 3 H).
13C NMR (CDCl3, 75.4 MHz): d = 150.2, 142.4, 128.1, 127.2,
125.9, 111.9, 76.7, 63.0, 25.7, 18.2, –4.9.
( )-2-(1-tert-Butyldimethylsilyloxybutyl-3-methylbutyl)prop-2-
en-1-ol (23)
Yield: 78%; colorless oil.
IR (film): 3360, 2958, 2895, 2854 cm–1.
1H NMR (CDCl3, 300 MHz): d = 5.05 (s, 1 H), 4.99 (s, 1 H), 4.33
(d, J = 13 Hz, 1 H), 4.12 (t, J = 12 Hz, 1 H), 4.10 (d, J = 13 Hz, 1
H), 1.68 (sept, J = 8 Hz, 1 H), 2.01 (s, 1 H), 1.51–1.40 (m, 2 H),
0.98–0.89 (m, 6 H), 0.90 (s, 9 H), 0.09 (s, 3 H), 0.06 (s, 3 H).
( )-2-[(tert-Butylimethylsilyloxy)(4-methoxyphenyl)methyl]-2-
prop-2-en-1-ol (18)
Yield: 86%; colorless viscous oil.
IR (film): 3370, 2955, 2910, 2849 cm–1.
13C NMR (CDCl3, 75.4 MHz): d = 149.8, 11.8, 75.0, 63.3, 45.9,
1H NMR (CDCl3, 300 MHz): d = 7.45 (d, J = 9 Hz, 2 H), 7.10 (d,
J = 9 Hz, 2 H), 5.50 (s, 1 H), 5.38 (s, 1 H), 5.30 (s, 1 H), 4.30 (d,
J = 12 Hz, 1 H), 4.12 (d, J = 12 Hz, 1 H), 4.01 (s, 3 H), 1.12 (s, 9
H), 0.28 (s, 3 H), 0.12 (s, 3 H).
25.8, 25.7, 24.3, 22.6, 18.0, –4.6, –5.0.
( )-2-(1-tert-Butyldimethylsilyloxyheptyl)-2-prop-2-en-1-ol (24)
Yield: 68%; colorless oil.
IR (film): 3369, 2950, 2915, 2854 cm–1.
13C NMR (CDCl3, 75.4 MHz): d = 158.7, 150.5, 134.6, 128.0,
1H NMR (CDCl3, 300 MHz): d = 5.05 (s, 1 H), 4.98 (s, 1 H), 4.26
(d, J = 13 Hz, 1 H), 4.23 (t, J = 3 Hz, 1 H), 4.10 (d, J = 13 Hz, 1 H),
2.8 (br s, exchangeable with D2O, 1 H), 1.59–1.55 (m, 2 H), 1.38–
1.22 (m, 8 H), 0.89 (s, 9 H), 0.87 (t, J = 7 Hz, 3 H), 0.09 (s, 3 H),
0.06 (s, 3 H).
127.1, 113.5, 111.7, 70.3, 63.2, 55.2, 25.7, 18.2, –3.5.
( )-2-[(2-Bromophenyl)(tert-butyldimethylsilyloxy)methyl]-2-
prop-2-en-1-ol (19)
Yield: 95%; colorless fluid oil.
IR (film): 3353, 2955, 2929, 2857 cm–1.
13C NMR (CDCl3, 75.4 MHz): d = 149.7, 111.4, 76.4, 63.5, 36.8,
1H NMR (CDCl3, 300 MHz): d = 7.52 (d, J = 7.7 Hz, 1 H), 7.44 (d,
J = 7.9 Hz, 1 H), 7.27 (t, J = 7.5 Hz, 1 H), 7.07 (t, J = 7.7 Hz, 1 H),
5.63 (s, 1 H), 5.13 (d, J = 4.4 Hz, 2 H), 4.04 (q, 2 H), 0.84 (s, 9 H),
0.05 (s, 3 H), –0.14 (s, 3 H).
31.9, 29.2, 25.9, 25.6, 22.7, 18.2, 14.1, –4.5, –4.7.
Epoxidation of Baylis–Hillman Adducts 17–25; General proce-
dure
To a solution of allylic alcohols 17–25 (1 mmol) in CH2Cl2 (25 mL)
at 0 °C was added m-chloroperbenzoic acid (204 mg, 1.18 mmol).
The resulting solution was stirred for 24 h until complete consump-
tion of starting material (verified by TLC). The mixture was washed
with an aq 10% solution of KOH (5 mL) and then extracted with
CH2Cl2 (30 mL). The organic layer was dried (Na2SO4) and the sol-
vent was removed under reduced pressure. The crude product was
purified by silica gel column chromatography (hexanes–EtOAc,
13C NMR (CDCl3, 75.4 MHz): d = 150.2, 142.2, 132.3, 128.0,
127.6, 127.3, 127.0, 119.2, 110.7, 74.7, 62.2, 25.8, 18.2, –4.6, –5.0.
( )-2-[(4-Bromophenyl)(tert-butyldimethylsilyloxy)meth-
yl]prop-2-en-1-ol (20)
Yield: 78%; colorless oil.
IR (film): 3351, 2948, 2920, 2863 cm–1.
Synthesis 2005, No. 14, 2297–2306 © Thieme Stuttgart · New York

2304
R. S. Porto et al.
PAPER
10%) to yield the corresponding epoxides, as a mixture of diaste-
reoisomers.
Hz, 1 H), 2.89 (d, J = 5 Hz, 1 H), 2.87 (d, J = 5 Hz, 1 H), 0.08 (s, 9
H), 0.03 (s, 3 H), –0.01 (s, 3 H).
13C NMR (CDCl3, 75.4 MHz): d = 134.0, 131.7, 128.7, 122.2, 74.7,
62.1, 61.0, 49.2, 26.3, 18.7, –4.2, –4.3.
anti-( )-2-[Hydroxy(phenyl)methyl]-2-oxyranylmethanol (26a)
Yield: 85%; yellow-tinged oil.
IR (film): 3449, 2927 cm–1.
1H NMR (CDCl3, 300 MHz): d = 7.37–7.24 (m, 5 H), 5.13 (s, 1 H),
3.92 (d, J = 12 Hz, 1 H), 3.73 (d, J = 12 Hz, 1 H), 3.49 (s, 1 H), 3.31
(d, J = 5 Hz, 1 H), 3.04 (d, J = 5 Hz, 1 H).
13C NMR (CDCl3, 75.4 MHz): d = 141.1, 128.7, 127.6, 125.3, 77.7,
72.2, 63.3, 41.1.
HRMS (70 eV): m/z calcd for C16H25BrO3Si: 372.0756; found:
372.0700.
anti-( )-2-[(6-Bromo-1,3-benzodioxol-5-yl)(tert-butyldimethyl-
silyloxy)methyl]-2-oxyranylmethanol (36)
Yield: 60%; colorless fluid oil.
IR (film): 3448, 2929 cm–1.
HRMS (70 eV): m/z calcd for C10H12O3: 180.07864; found:
180.07850.
1H NMR (CDCl3, 300 MHz): d = 7.05 (s, 1 H), 6.92 (s, 1 H), 6.0 (d,
J = 1.1 Hz, 2 H), 5.35 (s, 1 H), 4.14 (d, J = 11 Hz, 1 H), 4.09 (d,
J = 11 Hz, 1 H), 2.81 (d, J = 5 Hz, 1 H), 2.62 (d, J = 5 Hz, 1 H), 0.86
(s, 9 H), 0.09 (s, 3 H), –0.11 (s, 3 H).
13C NMR (CDCl3, 75 MHz): d = 147.9, 147.3, 132.3, 112.8, 111.6,
109.3, 101.7, 71.9, 61.5, 60.8, 47.0, 25.7, –4.7, –5.0.
anti-( )-2-[(tert-butyldimethylsilyloxy)(phenyl)methyl]-2-oxy-
ranylmethanol (32)
Yield: 76%; yellow-tinged oil.
IR (film): 3452, 2959 cm–1.
1H NMR (CDCl3, 300 MHz): d = 7.28–7.16 (m, 5 H), 4.63 (s, 1 H),
3.55 (d, J = 12 Hz, 1 H), 3.44 (d, J = 12 Hz, 1 H), 2.82 (d, J = 5 Hz,
1 H), 2.80 (d, J = 5 Hz, 1 H), 1.95 (s, 1 H), 0.80 (s, 9 H), –0.01 (s,
3 H), –0.16 (s, 3 H).
HRMS (70 eV): m/z calcd for C17H25BrO5Si: 416.0654; found:
416.01454.
anti-( )-2-(1-tert-Butyldimethylsilyloxybutyl)-2-oxyranylmeth-
anol (37)
Yield: 65%; colorless oil.
IR (film): 3370, 2969 cm–1.
13C NMR (CDCl3, 75.4 MHz): d = 128.1, 128.0, 127.8, 126.6, 74.7,
61.6, 60.7, 48.6, 29.7, 25.8, 18.2, –4.8, –4.9.
HRMS (70 eV): m/z calcd for C16H26O3Si: 294.1651; found:
294.1662.
1H NMR (CDCl3, 300 MHz): d = 4.15 (t, J = 5 Hz, 1 H), 2.94 (d,
J = 12 Hz, 1 H), 2.93 (d, J = 12 Hz, 1 H), 2.78 (d, J = 5 Hz, 1 H),
2.64 (d, J = 5 Hz, 1 H), 1.73–1.54 (m, 2 H), 0.88 (s, 9 H), 0.12 (s, 3
H), 0.09 (t, J = 5 Hz, 3 H), 0.05 (s, 3 H).
13C NMR (CDCl3, 75.4 MHz): d = 73.9, 61.4, 60.4, 59.6, 49.3, 48.5,
27.9, 25.8, 21.0, 18.2, 14.2, 10.6, 9.9, –4.3, –4.4.
anti-( )-2-[(tert-Butyldimethylsilyloxy)(4-methoxyphen-
yl)methyl]-2-oxyranylmethanol (33)
Yield: 75%; colorless oil.
IR (film): 3455, 2950 cm–1.
1H NMR (CDCl3, 300 MHz): d = 7.35 (d, J = 9 Hz, 2 H), 6.90 (d,
J = 9 Hz, 2 H), 4.75 (s, 1 H), 3.85 (s, 3 H), 3.69 (d, J = 12 Hz, 1 H),
3.61 (d, J = 12 Hz, 1 H), 2.92 (d, J = 5 Hz, 1 H), 2.89 (d, J = 5 Hz,
1 H), 0.95 (s, 9 H), 0.09 (s, 3 H), –0.05 (s, 3 H).
HRMS (70 eV): m/z calcd for C12H26O3Si: 246.1651; found:
246.1578.
anti-( )-2-(1-tert-Butyldimethylsilyloxy-3-methylbutyl)-2-oxy-
ranylmethanol (38)
Yield: 75%, colorless viscous oil.
IR (film): 3439, 2930 cm–1.
13C NMR (CDCl3, 75.4 MHz): d = 159.0, 132.3, 127.7, 113.4, 74.3,
60.8, 55.2, 48.6, 25.7, 18.2, –4.7, –4.8.
HRMS (70 eV): m/z calcd for C17H28O4Si: 324.1756; found:
324.1736.
1H NMR (CDCl3, 300 MHz): d = 4.12 (t, J = 12 Hz, 1 H), 3.87 (d,
J = 12 Hz, 1 H), 3.75 (d, J = 12 Hz, 1 H), 3.58 (dd, J = 4, 5 Hz, 2
H), 2.73 (d, J = 5 Hz, 1 H), 2.58 (d, J = 5 Hz, 1 H), 1.75 (sept, J = 7
Hz, 1 H), 0.94 (s, 3 H), 0.90 (s, 9 H), 0.87 (s, 3 H), 0.06 (s, 3 H),
0.05 (s, 3 H).
anti-( )-2-[(2-Bromophenyl)(tert-butyldimethylsilyloxy)meth-
yl]-2-oxyranylmethanol (34)
Yield: 82%; yellow-tinged oil.
IR (film): 3447, 2929 cm–1.
1H NMR (CDCl3, 300 MHz): d = 7.72–7.32 (m, 4 H), 5.64 (s, 1 H),
4.21 (d, J = 12 Hz, 1 H), 4.08 (d, J = 12 Hz, 1 H), 3.04 (d, J = 5 Hz,
1 H), 2.81 (d, J = 5 Hz, 1 H), 1.06 (s, 9 H), 0.31 (s, 3 H), 0.09 (s, 3
H).
13C NMR (CDCl3, 75.4 MHz): d = 75.2, 72.1, 60.5, 50.1, 48.5, 25.9,
24.1, 21.8, –4.2, –4.7. HRMS (70 eV): m/z calcd for C14H30O3Si:
274.1964; found: 274.1965.
anti-( )-2-(1-tert-Butyldimethylsilyloxyheptyl)-2-oxyranyl-
methanol (39)
Yield: 60%; colorless oil.
IR (film): 3442, 2930 cm–1.
1H NMR (CDCl3, 300 MHz): d = 3.58 (t, J = 4 Hz, 1 H), 3.87 (d,
J = 12 Hz, 1 H), 3.76 (d, J = 12 Hz, 1 H), 2.88 (d, J = 5 Hz, 1 H),
2.75 (d, J = 5 Hz, 1 H), 2,08 (s, 1 H), 1.62–1.10 (m, 13 H), 0.88 (s,
9 H), 0.12 (s, 3 H), 0.05 (s, 3 H).
13C NMR (CDCl3, 75 MHz): d = 138.9, 132.3, 130.1, 129.3, 127.2,
122.5, 72.0, 61.4, 60.9, 47.2, 25.8, –4.7, –5.0.
HRMS (70 eV): m/z calcd for C16H25BrO3Si: 372.0756; found:
372.0664.
anti-( )-2-[(4-Bromophenyl)(tert-butyldimethylsilyloxy)meth-
yl]-2-oxyranylmethanol (35)
13C NMR (CDCl3, 75 MHz): d = 73.3, 60.5, 60.4, 49.6, 35.0, 34.2,
Yield: 63%; colorless oil.
31.8, 29.4, 29.3, 25.8, 25.4, 22.6, 18.2, 14.1, –4.3, –4.7.
IR (film): 3447, 2929 cm–1.
HRMS (70 eV): m/z calcd for C16H34O3Si: 302.2277; found:
302.2119.
1H NMR (CDCl3, 300 MHz): d = 7.66 (d, J = 8 Hz, 2 H), 7.47 (d,
J = 8 Hz, 2 H), 4.90 (s, 1 H), 3.60 (d, J = 12 Hz, 1 H), 3.58 (d, J = 12
Synthesis 2005, No. 14, 2297–2306 © Thieme Stuttgart · New York

PAPER
Diastereoselective Epoxidation of Allylic Diols
2305
( )-4-(4-Methoxyphenyl)-6,6-dimethyl-1,5,7-trioxaspiro[2,5]oc-
tane (27a)
1H NMR (CDCl3, 300 MHz): d = 7.64 (m, 4 H), 7.37 (m, 6 H), 6.90
(s, 1 H), 6.88 (s, 1 H), 5.96 (d, J = 1 Hz, 1 H), 5.93 (d, J = 1 Hz, 1
H), 5.50 (s, 1 H), 5.33 (s, 1 H), 5.19 (s, 1 H), 4.13 (m, 2 H), 1.05 (s,
9 H), 0.90 (s, 9 H), 0.03 (s, 3 H), –0.09 (s, 3 H).
13C NMR (CDCl3, 75.4 MHz): d = 149.2, 147.3, 147.2, 135.5,
135.3, 133.5, 129.4, 127.4, 112.4, 111.7, 110.0, 108.5, 101.5, 73.6,
63.5, 26.8, 25.8, 19.3, 18.2, –4.7, –4.3.
To a stirred solution of 25 (0.05 g, 0.24 mmol) in 2,2-dimethoxypro-
pane (1.2 mL) was added a catalytic amount of camphorsulfonic
acid (0.5 mg). The resulting solution was stirred for 24 h at room
temperature. The solvent was evaporated under reduced pressure
and the residue was dissolved in EtOAc (20 mL). The organic phase
was washed with aq 5% solution of NaHCO3 (5 mL), brine (5 mL)
and dried (Na2SO4). The solvent was evaporated and the residue
was purified by silica gel column chromatography to provide 27a as
a colorless fluid oil; yield: 60%.
1H NMR (CDCl3, 500 MHz): d = 7.38 (d, J = 9 Hz, 2 H), 6.9 (d,
J = 9 Hz, 2 H), 5.35 (s, 1 H), 4.49 (d, J = 5 Hz, 1 H), 3.80 (s, 3 H),
3.62 (d, J = 5 Hz, 1 H), 2.5 (d, J = 7 Hz, 1 H), 2.24 (d, J = 7 Hz, 1
H), 1.65 (s, 3 H), 1.60 (s, 3 H).
Epoxides 41a and 41b
Prepared according to the general procedure for the epoxidation of
Baylis–Hillman adducts; yield: 98%.
41a
IR (film): 2957, 2929, 1487 cm–1.
1H NMR (CDCl3, 300 MHz): d = 7.69 (m, 4 H), 7.38 (m, 6 H), 7.00
(s, 1 H), 6.96 (s, 1 H), 5.98 (d, J = 1 Hz, 1 H), 5.92 (d, J = 1 Hz, 1
H), 5.36 (s, 1 H), 3.89 (d, J = 13 Hz, 1 H), 3.77 (d, J = 13 Hz, 1 H),
2.93 (d, J = 5 Hz, 1 H), 2.68 (d, J = 5 Hz, 1 H), 1.08 (s, 9 H), 0.85
(s, 9 H), 0.09 (s, 3 H), –0.12 (s, 3 H).
13C NMR (CDCl3, 75.4 MHz): d = 147.1, 144.2, 136.5, 133.0,
129.8, 127.7, 115.6, 108.0, 101.1, 78.8, 66.7, 56.9, 53.3, 22.6, 21.4,
20.1, 19.7, –4.3.
13C NMR (CDCl3, 125 MHz): d = 159.4, 129,6, 126.3, 113.1, 99.9,
73.1, 65.0, 55.2, 46.6, 29.7, 28.4, 19.9.
Methyl 2-[Hydroxy(4-methoxyphenyl)methyl]-2-oxyranecar-
boxylate (28)
To a stirred suspension of powdered, activated molecular sieves
(4Å, 0.7 g) in CH2Cl2 (10 mL) at –25 °C was added Ti(OPr-i)4 (0.22
mL, 0.74 mmol) and L-(+)-diisopropyl tartarate (0.18 mL, 0.09
mmol). After 30 min, the racemic adduct 2 (0.35 g, 1.57 mmol) in
CH2Cl2 (3 mL) was added and the mixture was stirred at the same
temperature for 1 h. Then, a TBHP solution in decane (0.29 mL,
0.85 mmol, 1.06 mol/L) was added dropwise. The mixture was then
stirred for 20 h at –25 °C. Then it was quenched by addition of ac-
etone (10 mL) and H2O (3.6 mL) and warmed to r.t. The resulting
emulsion was filtered through a pad of Celite and the filtrate was
dried (MgSO4) and concentrated. The residue was purified by silica
gel column chromatography to give epoxide 28; yield: 0.15 g
(40%).
41b
IR (film): 2957, 2929, 1487 cm–1.
1H NMR (CDCl3, 300 MHz): d = 7.67 (m, 4 H), 7.36 (m, 6 H), 6.97
(s, 1 H), 6.94 (s, 1 H), 5.97 (d, J = 1 Hz, 1 H), 5.90 (d, J = 1 Hz, 1
H), 5.33 (s, 1 H), 3.88 (d, J = 13 Hz, 1 H), 3.76 (d, J = 13 Hz, 1 H),
2.90 (d, J = 5 Hz, 1 H), 2.65 (d, J = 5 Hz, 1 H), 0.96 (s, 9 H), 0.54
(s, 9 H), 0.01 (s, 3 H), –0.15 (s, 3 H).
13C NMR (CDCl3, 75.4 MHz): d = 147.0, 144.1, 136.2, 132.9,
129.7, 127.4, 115.3, 107.8, 100.9, 78.5, 66.5, 56.8, 53.1, 22.4, 21.3,
19.9, 19.5, –4.6.
IR (film): 3443, 2926, 1730 cm–1.
1H NMR (CDCl3, 500 MHz): d = 7.31 (d, J = 10 Hz, 2 H), 6.85 (d,
J = 10 Hz, 2 H), 5.16 (s, 1 H), 3.79 (s, 3 H), 3.72 (s, 3 H), 3.12 (d,
J = 5 Hz, 1 H), 2.83 (d, J = 5 Hz, 1 H), 2.61 (s, 1 H).
13C NMR (CDCl3, 125 MHz): d = 177.7, 159.5, 130.2, 128.2, 113.6,
71.2, 58.9, 55.1, 52.6, 49.5.
Epoxide 43
Step 1: To a mixture of anhyd CH2Cl2 (10 mL) and anhyd DMSO
(0.17 mL, 1.25 mmol) was added oxalyl chloride (0.107 mL, 1.25
mmol) at –78 °C under argon. After stirring for 20 min, a solution
of the mono-protected diol 35 (0.162 g, 0.5 mmol) in CH2Cl2 (5 mL)
was added. The mixture was stirred for 50 min at the same temper-
ature. After this time, Et3N (0.71 mL, 2.5 mmol) was added and then
the mixture was warmed to r.t. After stirring for 50 min, aq ammo-
nia (10 mL) was added and the resulting mixture was extracted with
CHCl3 (3 × 5 mL). The combined organic layers were washed with
brine (2 × 10 mL), dried (Na2SO4), filtered and concentrated under
reduced pressure. The crude product was purified by silica gel col-
umn chromatography to give 0.144 g (90%) of the corresponding al-
dehyde, which was used in the next step.
2-Hydroxymethyl-2-oxiranyl-4-methoxyphenylmethanol (30)
Prepared according to the general procedure for the epoxidation of
Baylis–Hillman adducts; yield: 59%.
IR (film): 3439, 2923 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.30 (d, J = 9 Hz, 2 H), 6.90 (d,
J = 9 Hz, 2 H), 4,95 (s, 1 H), 3.81 (s, 3 H), 3,57 (d, J = 12 Hz, 1 H),
3,52 (d, J = 12 Hz, 1 H), 3.16 (d, J = 5 Hz, 1 H), 2.89 (d, J = 5 Hz,
1 H), 2.21 (s, 1 H), 1.62 (s, 1 H).
13C NMR (75.4 MHz, CDCl3): d = 159.6, 128.5, 127.6, 114.0, 75.3,
66.4, 61.5, 55.2, 47.4.
Intermediate Aldehyde
IR (film): 2957, 1714, 1569 cm–1.
1H NMR (CDCl3, 300 MHz): d = 9.09 (s, 1 H), 7.41 (d, J = 9 Hz, 2
H), 7.21 (d, J = 9 Hz, 2 H), 5.27 (s, 1 H), 2.86 (d, J = 5 Hz, 1 H),
2.69 (d, J = 5 Hz, 1 H), 0.81 (s, 9 H), 0.05 (s, 3 H), –0.12 (s, 3 H).
13C NMR (CDCl3, 75.4 MHz): d = 208.6, 130.1, 129.3, 128.7,
120.9, 77.09, 65.5, 51.8, 21.7, 20.0, –4.4.
5-Bromo-6-[(1-tert-butyldimethylsilyloxy)-2-(tert-butyldiphe-
nylsilyloxymethyl)allyl]-1,3-benzodioxole (40)
A mixture of the allylic diol 21 (0.2 g, 0.5 mmol), DMAP (1.5 mg,
0.0125 mmol) and Et3N (0.14 mL, 1 mmol) in CH2Cl2 (5 mL) was
stirred for 5 min at 0 °C. tert-Butyldiphenylsilyl chloride (0.2 g,
0.75 mmol) was then added at the same temperature. After the ad-
dition, the ice bath was removed and the mixture was stirred at r.t.
under N2 for 18 h. The mixture was quenched with hexane (10 mL).
The hexane phase was washed with brine (2 × 5 mL) and distilled
H2O (5 mL), and dried (Na2SO4). After evaporation of the solvent,
the residue was purified by silica gel column chromatography;
Yield: 93%.
Step 2: To a solution of the aldehyde (0.09 g) prepared as described
above in t-BuOH (15 mL), was added 2-methylbut-2-ene (1.5 mL,
14.4 mmol) and the reaction temperature was lowered to 0 °C. After
that, a solution of NaClO2 (0.25 g, 2.76 mmol) and NaH2PO4 (0.119
g, 2.07 mmol) in distilled H2O (1 mL) was added dropwise. The re-
sulting mixture was stirred for 16 h. The mixture was then concen-
trated under reduced pressure. The residue was diluted in H2O,
acidified with aq 10% solution of HCl (pH 3) and extracted with
IR (film): 2955, 2930, 1503, 1233 cm–1.
Synthesis 2005, No. 14, 2297–2306 © Thieme Stuttgart · New York

2306
R. S. Porto et al.
PAPER
Et2O (2 × 20 mL). The organic phase was dried (MgSO4) and the
solvent removed under reduced pressure. No additional purification
was necessary.
IR (film): 2963, 1728, 1580 cm–1.
1H NMR (CDCl3, 300 MHz): d = 9.93 (s, 1 H), 7.36 (d, J = 10 Hz,
2 H), 7.29 (d, J = 10 Hz, 2 H), 4.95 (s, 1 H), 3.29 (d, J = 5 Hz, 1 H),
3.08 (d, J = 5 Hz, 1 H), 0.79 (s, 9 H), 0.02 (s, 3 H), –0.09 (s, 3 H).
(4) For some examples of syn diastereoselectivity in
homogeneous hydrogenation of Baylis–Hillman adducts,
see: (a) Brown, J. M.; Cutting, I. J. Chem. Soc., Chem.
Commun. 1985, 578. (b) Brown, J. M. Angew. Chem., Int.
Ed. Engl. 1987, 26, 190. (c) Brown, J. M.; Cutting, I.;
James, A. P. Bull. Soc. Chim. Fr. 1988, 211.
(d) Yamamoto, K.; Takagi, M.; Tsuji, J. Bull. Chem. Soc.
Jpn. 1988, 319. (e) Brown, J. M.; Rose, M.; Knight, F. I.;
Wienand, A. Recl. Trav. Chim. Pays-Bas 1995, 114, 247.
(f) Brown, J. M.; Evans, P. L.; James, A. P. Org. Synth.
1990, 68, 64. (g) Farington, E.; Franchini, M. C.; Brown, J.
M. Chem. Commun. 1998, 277. (h) Mateus, C. R.; Almeida,
W. P.; Coelho, F. Tetrahedron Lett. 2000, 41, 2533.
(i) Coelho, F.; Almeida, W. P.; Mateus, C. R.; Furtado, L.
D.; Gouveia, J. C. F. Arkivoc 2003, x, 443; www.arkat-
usa.org. (j) Bouzide, A. Org. Lett. 2002, 4, 1347.
(5) (a) Bailey, M.; Markó, I. E.; Ollis, W. D. Tetrahedron Lett.
1991, 32, 2687. (b) Bailey, M.; Markó, I. E.; Ollis, W. D.
Tetrahedron Lett. 1990, 31, 4509.
13C NMR (CDCl3, 75.4 MHz): d = 185.1, 130.5, 130.2, 128.8,
120.3, 78.4, 59.8, 51.1, 21.6, –4.3.
Acknowledgment
The authors thank FAPESP for a fellowship to RSP and for financi-
al support. The authors are grateful to Prof. C. H. Collins for the
English revision of this manuscript. FC thanks CNPq for a research
fellowship.
(6) (a) Iwabuchi, Y.; Furukawa, M.; Esumi, T.; Hatakeiyama, S.
Chem. Commun. 2001, 2030. (b) Iwabuchi, Y.; Nakatami,
M.; Yokoyama, M.; Hatakeiyama, S. J. Am. Chem. Soc.
1999, 121, 10219.
(7) (a) Maruyama, K.; Ueda, M.; Sasaki, S.; Iwata, Y.;
Miyazawa, M.; Miyashita, M. Tetrahedron Lett. 1998, 39,
4517. (b) Jorgensen, K. B.; Koshino, H.; Nakata, T.
Heterocycles 1998, 47, 679. (c) Kurihara, M.; Ishii, K.;
Kasahara, Y.; Kameda, M.; Pathak, A. K.; Miyata, N. Chem.
Lett. 1997, 1015. (d) Tomioka, H.; Susuki, T.; Oshima, K.;
Nozaki, H. Tetrahedron Lett. 1982, 23, 3387.
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Synthesis 2005, No. 14, 2297–2306 © Thieme Stuttgart · New York