Alkenyl β-d-galactopyranoside derivatives as efficient chiral templates in stereoselective cyclopropanation and epoxidation reactions

Article abstract of DOI:10.1016/j.tetasy.2009.12.003

The synthesis of a wide range of alkenyl 4,6-O-(S)-benzylidene-β-d-galactopyranosides is described. The cyclopropanation and epoxidation reactions of these compounds were developed. Cyclopropanation reactions took place with high stereoselectivity giving diastereomeric excesses of up to 100%. As a part of our aim in studying hydroxyl-directed reactions, their epoxidation with m-CPBA was carried out. High diastereomeric excesses (80-100%) were obtained when the hydroxyl group at C-2 of the auxiliary was unprotected. The β-d-galactopyranoside moiety constitutes as an interesting auxiliary, due to its efficient chirality transfer capability as well as providing a way to obtain a variety of glycolipid derivatives.

Full text of DOI:10.1016/j.tetasy.2009.12.003

Tetrahedron: Asymmetry 21 (2010) 81–95
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Alkenyl b-D-galactopyranoside derivatives as efficient chiral templates
in stereoselective cyclopropanation and epoxidation reactions
*
*
José M. Vega-Pérez , Ignacio Periñán, Carlos Palo-Nieto, Margarita Vega-Holm, Fernando Iglesias-Guerra
Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, E-41071 SEVILLA, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of a wide range of alkenyl 4,6-O-(S)-benzylidene-b-
D
-galactopyranosides is described. The
Received 18 November 2009
Accepted 9 December 2009
Available online 6 January 2010
cyclopropanation and epoxidation reactions of these compounds were developed. Cyclopropanation reac-
tions took place with high stereoselectivity giving diastereomeric excesses of up to 100%. As a part of our
aim in studying hydroxyl-directed reactions, their epoxidation with m-CPBA was carried out. High diaste-
reomeric excesses (80–100%) were obtained when the hydroxyl group at C-2 of the auxiliary was unpro-
tected. The b-D-galactopyranoside moiety constitutes as an interesting auxiliary, due to its efficient
chirality transfer capability as well as providing a way to obtain a variety of glycolipid derivatives.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
chiral auxiliaries.7 There are only a few precedents for the stereo-
selective synthesis of cyclopropanes using carbohydrates as chiral
Given the close relationship between therapeutic activity and
chirality, the preparation of enantiomerically pure compounds, to
be tested and/or used as potential drugs, is currently a great chal-
lenge in organic and pharmaceutical chemistries. The use of chiral
auxiliaries to achieve stereoselectivity is an important strategy in
asymmetric synthesis in order to obtain enantiomerically enriched
compounds.1 In this context, carbohydrates, which contain several
functional groups and stereogenic centres in one molecular unit,
are effective tools as chiral inducers.2,3
One of our lines of research, the search for new methods to pre-
pare enantiomerically pure substances, is centred on the develop-
ment of methods for the synthesis of synthetic and/or functionally
relevant functions, such as the cyclopropanes and oxiranes, via the
stereoselective transformation of alkenes, employing carbohy-
drates as chiral inducers. The fragment, which contains the double
bond to be transformed, is incorporated into different positions of
the sugar residue by means of different organic functions.
Due to the presence of cyclopropane rings in a variety of natural
products and biologically active compounds,4 and their nature as
versatile synthetic intermediaries for the preparation of more func-
tionalised cycloalkanes and acyclic compounds,5 the development
of efficient methods for the synthesis of chiral non-racemic cyclo-
propane moieties is an important aim in asymmetric synthesis.
General methods for this stereoselective synthesis have recently
been reviewed.6 One synthetic strategy is based on the stereoselec-
tive addition of the methylene group to substituted allyllic alcohols
auxiliaries.8–12 Our group has recently published the stereoselec-
tive cyclopropanation (using the diiodomethane/diethyl zinc sys-
tem) of a wide range of alkenes linked via an acetal function to
different backbones of sugar moieties.13,14 It is important to note
that the union of the olefin to the carbohydrate via an acetal func-
tion allowed the easy separation of the new chiral cyclopropane
fragment and the chiral auxiliary by mild acid hydrolysis.
Chiral epoxides are widely employed in organic synthesis be-
cause they are useful synthetic intermediates that can easily
be transformed into a variety of target molecules15 (via their open-
ing reaction which allows the obtention of 1,2-difunctionalised
compounds and the formation of new carbon–carbon bonds). The
functional group is itself an essential structural moiety of many
natural products and biologically active compounds.16 Its chemical
reactivity is responsible for the biological activity exhibited by the
compounds that contain the function; certain glycosyl glycidols
(oxiranes derived from alkenyl glycosides) have cytotoxic activity
and can be used as alkylating agents in anticancer chemotherapy.17
The development of efficient methods to gain access to chiral epox-
ides with high enantiomeric excesses is an important goal of many
research groups, including our own.
The enantioselective epoxidation of non-functionalised olefins
is one of the most useful processes in synthetic transformations
for the introduction of functional groups into organic molecules.
Over the last few years we have developed methods for the stere-
oselective epoxidation of olefins, involving the use of chiral cata-
lysts or chiral auxiliaries, both of which are derived from sugars.
With regard to the first, we have recently described the synthesis
of new chiral ketones and their use as catalysts in the enantioselec-
tive dioxirane-mediated epoxidation of a wide range of arylalk-
enes.18 For the second, we have developed the stereoselective
and to
a,b-unsaturated carbonyl compounds joined to different
* Corresponding authors. Tel./fax: +34 95 4556737.
E-mail addresses: vega@us.es (J.M. Vega-Pérez), iglesias@us.es (F. Iglesias-
Guerra).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.12.003

82
J. M. Vega-Pérez et al. / Tetrahedron: Asymmetry 21 (2010) 81–95
epoxidation of olefins with m-CPBA. The olefinic chain was joined
to different positions of a sugar molecule, acting as a chiral auxil-
iary via various functions: glycoside, amide and acetal. The chiral
epoxyalkyl glycosides,19 epoxyamides20 and epoxyacetals21,22 ob-
tained can be transformed into different types of compound. This
method has enabled us to synthesise derivatives of glycosylglycer-
ol analogues which have been used as an alkylating-agent carrier
system23 and phenylisoserine precursors21,22 whose acetal func-
tion can be easily hydrolysed in the organism to separate the active
fraction of the sugar moiety.
Herein we continue to investigate the development of effective
methods for the selective cyclopropanation and epoxidation of al-
kenes. In the present case, the substrates chosen as carriers of the
double bond for the stereoselective transformations are a wide
range of allyl alcohols that join to the chiral auxiliary via a glyco-
2. Results and discussion
Herein we report the highly diastereoselective cyclopropana-
tion and epoxidation reactions of substituted allylic alcohols linked
to a carbohydrate moiety readily available from commercial
a-D-acetobromogalactose 1. The double bond was incorporated
into the sugar by a simple glycosidation reaction, and via a short
synthetic sequence we obtained the new alkenyl 4,6-O-(S)-benzyl-
idene-b-D-galactopyranosides 2–8. By this means we achieved a set
of functionalised substances with a well-defined stereochemistry,
and with a double bond susceptible to transformation into com-
pounds with diverse but constitutionally similar chemical features
(Scheme 1). These alkenyl derivatives are obtained in good chem-
ical yields and as single diastereoisomers. In all cases, the proton of
4,6-O-(S)-benzylidene acetal appears as a singlet between 5.57 and
5.55 ppm, while the proton at the anomeric position appears as a
doublet at around 4.30 ppm in those cases where its signal is
resolved.
In order to have a higher number of substrates to study the
reactions and to analyse the effect of the free hydroxyl groups at
the 2- and 3-position of the sugar and/or the aromatic residues
of the protecting groups introduced into both the chemical and ste-
reochemical yields obtained in the cyclopropanation and epoxida-
tion reactions, and at the same time to attempt to resolve the
possible problems caused by the solubilities of the alkenyl deriva-
tives in the solvents used in these reactions (caused by the pres-
ence of the OH at the 2- and 3-position of the sugar), the
compounds 9–15 were obtained by the introduction of benzyl
ethers (Scheme 2). In all cases, the signals for the two pairs of dia-
stereotopic benzyl protons (2-OCH2Ph and 3-OCH2Ph) appear be-
tween 4.9 and 4.7 ppm.
sidic bond with D-galactose as the carbohydrate inducer of chiral-
ity. We chose this carbohydrate as the auxiliary; (a) because
there are few references describing the use of chiral auxiliaries de-
rived from
thus to assess its capacity as a chirality agent; and (b) because
D
-galactose in these reactions on double bonds,24 and
D-
galactose is a frequent sugar in glycolipid complexes such as glyc-
erolipids, phosphatidic acids and sphingolipids, substances that
have gained great interest as regulatory agents of cell proliferation,
and thus are possibly useful in the treatment of cancer.25 The syn-
thesis of the derivatives or analogues of these natural products is a
focus of attention. On this point it is of interest that the stereose-
lective synthesis of the cyclopropane and oxirane functions of the
substituents on the anomeric position of D-galactosyl derivatives is
shown to be an effective procedure for obtaining synthetic inter-
mediaries and analogues of those natural compounds for their sub-
sequent biological evaluation.
It has been reported that b-D-glucopyranosides with a free hy-
droxyl group at the 2-position are efficient chiral auxiliaries for
stereoselective reactions of cyclopropanation and epoxidation of
allyl alcohols present on the aglyclone.8,19,26 The presence of the
OH at the 2-position of the sugar is a determinant for the stereose-
lectivity of the reactions of epoxidation and cyclopropanation of al-
Ph
OAc
O
AcO
AcO
O
R1
i
O
O
O
R3
lyl b-D-glucopyranosides, and can be attributed to the OH
HO
presumably acting as an anchor point of the reagent from which
it is transferred preferentially to one of the faces of the double
bond which determines the configuration of the major diastereo-
isomer obtained. Thus, our next aim in adding to the range of com-
pounds in which we were going to carry out both reactions of
transformation of the double bond was the synthesis of the 3-O-
benzylated derivatives. We obtained compounds that conserve a
free OH at the 2-position of the sugar and are soluble in the
appropriate solvents, in order to evaluate whether in these new
galactosyl derivatives the 2-OH group is determinant in the stereo-
chemical control of the reaction. The bibliography describes the
AcO
OH
Br
R2
2 R1 = H , R2 = H, R3 = H
1
3 R1 = H , R2 = H, R3 = Ph
4 R1 = H , R2 = H, R3 = Me
5 R1 = H , R2 = H, R3 = n-C7H15
6 R1 = H , R2 = Me, R3 = Me
7 R1 = Me , R2 = H, R3 = H
8 R1 = Me , R2 = H, R3 = Ph
Scheme 1. Reagents and conditions: (i) (1) HOCH2CR1@CR2R3/MeNO2–PhMe (1:1)/
Hg(CN)2/50 °C/2–3 h; (2) NaMeO/MeOH; (3) PhCH(OMe)2/MeCN/CSA.
Ph
O
Ph
O
O
O
R1
R1
i
O
O
O
R3
O
R3
HO
BnO
OH
2−8
OBn
R2
R2
9 R1 = H , R2 = H, R3 = H
10 R1 = H , R2 = H, R3 = Ph
11 R1 = H , R2 = H, R3 = Me
12 R1 = H , R2 = H, R3 = n-C7H15
13 R1 = H , R2 = Me, R3 = Me
14 R1 = Me , R2 = H, R3 = H
15 R1 = Me , R2 = H, R3 = Ph
Scheme 2. Reagents: (i) BnBr/KOH/18-crown-6/THF.

J. M. Vega-Pérez et al. / Tetrahedron: Asymmetry 21 (2010) 81–95
83
Ph
Ph
O
O
O
O
R1
R1
i
O
O
O
R3
O
R3
HO
BnO
OH
OH
R2
R2
16 R1 = H , R2 = H, R3 = H
2−8
17 R1 = H , R2 = H, R3 = Ph
18 R1 = H , R2 = H, R3 = Me
19 R1 = H , R2 = H, R3 = n-C7H15
20 R1 = H , R2 = Me, R3 = Me
21 R1 = Me , R2 = H, R3 = H
22 R1 = Me , R2 = H, R3 = Ph
Scheme 3. Reagents: (i) BnBr/KOH/18-crown-6/THF.
Ph
Ph
O
O
O
O
R1
R1
i
O
O
O
R3
O
R3
HO
HO
OH
OH
R2
R2
23 R1 = H , R2 = H, R3 = Ph
3 R1 = H , R2 = H, R3 = Ph
6 R1 = H , R2 = Me, R3 = Me
24 R1 = H , R2 = Me, R3 = Me
Scheme 4. Reagents: (i) CH2I2/ZnEt2/CH2Cl2.
benzylation mediated by butyltin oxide which takes place with
high chemoselectivity towards the 3-position of the allyl 4,6-O-
benzylidene-b-galactopyranoside to give the 3-O-benzyl ether, a
reaction that requires heating and reaction times of around
24 h.27 We have developed a method for the selective monobenzy-
lation of the hydroxyl at position 3 of the sugar, using the same
method as for the dibenzylation, although with rigorous control
of the equivalents of reagents and, mainly, of the reaction time
(20–30 min) (for general conditions see Experimental) (Scheme 3).
We achieved marked improvements over the previously described
procedure with regard to shorter reaction times, no need for heat-
ing and applicability to a variety of alkenyl 4,6-O-(S)-benzylidene-
b-D-galactopyranosides with products 16–22 being obtained. In all
cases the signal due to the benzyl protons appears at around
4.7 ppm.
The next step was to tackle the cyclopropanation of the new
alkenyl derivatives by the general method of Simmons–Smith. This
cyclopropanation reaction had been studied in allyl b-D-glucopyr-
use CH2Cl2 as the solvent, and chose for this assay, compounds 3
and 6 (Scheme 4). Compounds 23 and 24 were obtained in 57%
and 22% of diastereoisomeric excess, respectively (determined by
1H NMR).
For the assays of the cyclopropanation reaction in toluene, we
chose the alkenyl glycoside analogues of 2 and 3, which are soluble
in that solvent and hence give the corresponding dibenzylated and
monobenzylated derivatives. The cyclopropanation reaction of
compounds 10 and 13 (2,3-di-O-benzyl-derived substrates) in tol-
uene does not take place. We attribute this to the steric hindrance
exerted by the benzyl group at the 2-position of the sugar,
obstructing the access of the reagent to the double bond. However,
the reaction of compounds 17 and 20 (3-O-benzyl-derived) yielded
compounds 25 and 26 with 100% diastereoisomeric excess. This led
us to subject the remaining 3-O-benzylated derivatives, com-
pounds 18, 19 and 22, to the cyclopropanation reaction to give
compounds 27, 28 and 29 (Scheme 5). The excesses continued to
be high: 74–100% (Table 1).
anosides in toluene, which takes place with high diastereoisomeric
excesses.8b,9–12 As our products, with a free OH at at the 2- and 3-
position of the sugar, are not very soluble in toluene, we decided to
All the cyclopropyl derivatives with a Ph at the 2-position of the
cyclopropane ring present the signals of the 2H of the methylenic
bridge at around 0.9–1.0 ppm while those of the H of the methines
Ph
O
Ph
O
O
O
R1
R1
i
O
O
O
R3
O
R3
BnO
BnO
OH
OH
R2
R2
17 R1 = H , R2 = H, R3 = Ph
25 R1 = H , R2 = H, R3 = Ph
26 R1 = H , R2 = Me, R3 = Me
27 R1 = H , R2 = H, R3 = Me
18 R1 = H , R2 = H, R3 = Me
19 R1 = H , R2 = H, R3 = n-C7H15
20 R1 = H , R2 = Me, R3 = Me
22 R1 = Me , R2 = H, R3 = Ph
28 R1 = H , R2 = H, R3 = n-C7H15
29 R1 = Me , R2 = H, R3 = Ph
Scheme 5. Reagents: (i) CH2I2/ZnEt2/PhCH3.

84
J. M. Vega-Pérez et al. / Tetrahedron: Asymmetry 21 (2010) 81–95
Table 1
variety of compounds by oxirane opening, for example, glycolipids,
in the present context: the employment of -galactose derivatives
Cyclopropanation of alkenyl galactopyranosides 17–20 and 22 produced via Scheme 5
D
Entry Starting
compound product
Reaction Yielda (%) Deb (%) Major cyclopropane
as chiral template acquires added value. Our group has already de-
scribed the use of this method for the synthesis of chiral epox-
yalkyl glucosides with high diastereoisomeric excesses,19 and
derivatives of glycosylglycerol analogues that have been used as
an alkylating agent carrier system.23 The aim of this work was to
obtain epoxyalkyl galactopyranosides and to study the influence
of both the configuration of the sugar (galacto) and the role of
the OH at the 2- and 3-position of the sugar on the stereoselectivity
of the epoxidation reaction. In all cases the reaction was performed
in chloroform at ꢀ15 °C for the time necessary until plate detection
showed that all the starting material had been consumed (for reac-
tion conditions see Experimental). The reaction of compounds 2–8
(with the free OH at the 2- and 3-position of the sugar) yielded
compounds 32–38. Compounds 9, 10 and 14 (2,3-di-O-benzyl
derivatives) yielded the compounds 39–41. The epoxidation of
the 3-O-benzyl derivatives 16–19, 21 and 22 yielded compounds
42–47 (Scheme 7).
configuration
1
2
3
4
5
17
18
19
20
22
25
27
28
26
29
95
91
91
91
67
100
84
100
100
78
(2S,3S)
(2S,3S)
(2S,3S)
(2S)
(2S,3R)
a
Yields refer to compounds obtained in each reaction after isolation and
purification.
b
Determined by relative integration in the 1H NMR spectra of reaction mixture.
of the cycle between 1.5 ppm and 1.8 ppm. For the 2-alkyl cyclo-
propyl derivatives, those signals appeared at around 0.2–0.5 ppm
and 0.7–0.9 ppm, respectively.
In order to assign the absolute configuration of the stereogenic
centres generated in the cyclopropanation reaction, the cyclopro-
pyl derivatives 25 and 28 (obtained with some 100% diastereoiso-
meric excess) were treated with triflic anhydride in pyridine;
subsequent heating in aqueous DMF in the presence of pyridine
yielded the enantiomerically pure cyclopropylcarbinols 30 and
31.9 Comparison of the specific rotations of these compounds with
those reported in the literature enabled us to assign the absolute
stereochemistry of the cyclopropane ring for compounds 3014,28
and 3114 (Scheme 6); in both cases the enantiomer obtained had
an (S,S)-configuration. The reactive face is the same in the two
cases—its notation being (Si,Si) for compound 17 (with one aro-
matic substituent on carbon three of the allyl moiety) and (Si,Re)
for compound 19 (with one alkyl substituent on carbon three). It
should be emphasised that our research group had already de-
scribed the enantioselective synthesis of the cyclopropylcarbinol
enantiomers of 30 and 31, employed as a chiral auxiliary 1,2-O-iso-
The diastereoisomeric excesses were established by 1H NMR
(Table 2). For their analysis, the epoxyalkyl b-D-galactopyranosides
were grouped into three groups. The first group comprises those
substrates with a free OH at the 2- and 3-position of the sugar res-
idue (compounds 32–38); the second group comprises those epox-
ides obtained by using 2,3-di-O-benzyl derivative as a chiral
inducer (compounds 39–41); and the third group comprises those
in which the chiral auxiliary is a 3-O-benzyl derivative (com-
pounds 42–47). As can be seen in Table 2, the compounds obtained
with the largest diastereoisomeric excesses are 32–38 and 42–47,
with values between 77% and 100%. However, the excesses ob-
tained fall drastically (9–23%), and in one case to zero, for com-
pounds 39–41. This demonstrates that the presence of the OH at
the 2-position of the sugar is the determinant for the stereoselec-
tivity of the epoxidation reaction of the double bond with m-CPBA
attributed to the formation of a hydrogen bridge between the OH
group and the peroxyacid.
propylidene-a-D-xylofuranose and incorporating the alkene via an
acetal function that is readily cleaved off.14 The configurations of
the other cyclopropanes listed in Table 1 were established from
analysis of the chemical shifts of the protons and the carbons of
the cyclopropane system and anomeric position in the NMR data.
The stereoselectivity generated due to the directing role of the
group at the 2-position of the sugar able to form hydrogen bridges
with the peroxyacid has already been described in the epoxidation
reactions of alkenyl b-
at the 2-position of the sugar) and by ourselves in the epoxidation
reaction of alkenyl glycoside derived from N-acetyl- -glucosamine
D
-glucopyranoside derivatives26 (OH group
Ph
O
D
(acetamido group on 2),19 in both cases the reactive face being Re.
Our group has also described the stereoselectivity in the epoxida-
tion reaction of propenylidene acetals derived from glucopyrano-
sides, allopyranosides, glucofuranosides and xylofuranosides, and
how the stereochemistry of the major oxirane obtained depends
on the configuration of the sugar residue employed as a chiral aux-
iliary and whether the OH at the 3-position of the sugar is free or
protected; the asymmetric induction is greater when it is free.20,21
In order to assign the configuration to the stereogenic centres in
the oxirane ring formed in the epoxidation reaction, the chemical
shifts of the easily identifiable protons and carbons must be ana-
O
R1
O
O
R3
BnO
OH
R2
25 R1 = H , R2 = H, R3 = Ph
28 R1 = H , R2 = H, R3 = n-C7H15
i
i
(S)
(S)
lysed and compared with the signals of epoxyalkyl b-D-glucopyran-
HO
HO
Ph
oside analogues previously described.19 For this, we compared the
chemical displacements and profile of the signals of the protons
and carbons of epoxyalkyl 2-acetamido-(R)-4,6-O-benzylidene-2-
(S)
(S)
(+)-30
(+)-31
deoxy-b-D-glucopyranoside analogues 49–52 (Scheme 8), whose
Scheme 6. Reagents and conditions: (i) (1) Tf2O/Py (95%); (2) DMF/Py/H2O/160 °C.
epoxyalkyl moieties on the anomeric position are analogous to
those present on compounds 32–47 (Table 3).
The second part of the study, which was within our line of work
centred on the development of new sugar-derived chiral inducers
for hydroxyl-group-directed reactions, was to subject the newly
synthesised b-allyl galactopyranosides to an epoxidation reaction
with m-CPBA. This general method is of interest not only because
it enables access to chiral-substituted epoxyalcohols, but also be-
cause it undoubtedly provides a procedure for the synthesis of a
In most of the cases examined (as shown in Table 3), the major
stereoisomer presents a lower chemical shift in 1H NMR for the
anomeric proton, and a higher chemical displacement for the ano-
meric carbon in 13C NMR. At the same time, the signals of the car-
bons of the oxirane ring and of the allyl methylene appear at lower
values of chemical displacement for the major stereoisomer than

J. M. Vega-Pérez et al. / Tetrahedron: Asymmetry 21 (2010) 81–95
85
Ph
Ph
O
O
O
O
R1
R1
O
O
O
O
R3
O
R3
i
HO
HO
OH
OH
R2
R2
2 R1 = H , R2 = H, R3 = H
3 R1 = H , R2 = H, R3 = Ph
4 R1 = H , R2 = H, R3 = Me
32 R1 = H , R2 = H, R3 = H
33 R1 = H , R2 = H, R3 = Ph
34 R1 = H , R2 = H, R3 = Me
5 R1 = H , R2 = H, R3 = n-C7H15
6 R1 = H , R2 = Me, R3 = Me
7 R1 = Me , R2 = H, R3 = H
8 R1 = Me , R2 = H, R3 = Ph
35 R1 = H , R2 = H, R3 = n-C7H15
36 R1 = H , R2 = Me, R3 = Me
37 R1 = Me , R2 = H, R3 = H
38 R1 = Me , R2 = H, R3 = Ph
Ph
O
Ph
O
O
O
R1
R1
O
O
O
O
R3
O
R3
i
BnO
BnO
OBn
OBn
R2
R2
9 R1 = H , R2 = H, R3 = H
10 R1 = H , R2 = H, R3 = Ph
14 R1 = Me , R2 = H, R3 = H
39 R1 = H , R2 = H, R3 = H
40 R1 = H , R2 = H, R3 = Ph
41 R1 = Me , R2 = H, R3 = H
Ph
O
Ph
O
O
O
R1
R1
i
O
O
O
O
R3
O
R3
BnO
BnO
OH
OH
R2
R2
42 R1 = H , R2 = H, R3 = H
43 R1 = H , R2 = H, R3 = Ph
44 R1 = H , R2 = H, R3 = Me
16 R1 = H , R2 = H, R3 = H
17 R1 = H , R2 = H, R3 = Ph
18 R1 = H , R2 = H, R3 = Me
45 R1 = H , R2 = H, R3 = n-C7H15
46 R1 = Me , R2 = H, R3 = H
47 R1 = Me , R2 = H, R3 = Ph
19 R1 = H , R2 = H, R3 = n-C7H15
21 R1 = Me , R2 = H, R3 = H
22 R1 = Me , R2 = H, R3 = Ph
Scheme 7. Reagents and conditions: (i) m-CPBA/CHCl3/ꢀ15 °C.
for the minor stereoisomer in those compounds whose signals are
spread for each diastereoisomer.
Table 2
Epoxidation of alkenyl galactopyranosides 2–10, 14, 16–19, 21 and 22 produced via
Scheme 7
From these correlation studies we were able to assign the nota-
tion for the more reactive face (in all cases studied it was always
the same): Re,Re in compounds with one aromatic substituent on
the C-3; Re in compounds whereby both substituents on the C-3
are the same and Re,Si in compounds with one alkyl substituent
on C-3; as well as the absolute configuration of the major stereo-
isomer for compounds 32–47 as shown in Table 3.
Entry
Starting
compound
Reaction
product
Yielda (%)
Deb (%)
Major oxirane
configurationc
1
2
2
3
4
5
6
7
8
9
10
14
16
17
18
19
21
22
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
63
72
56
74
92
79
80
90
72
90
61
87
98
80
79
85
100
85
80
80
23
88
76
23
9
(2R)
(2S,3S)
(2S,3S)
(2S,3S)
(2S)
(2R)
(2S,3S)
(2R)
(2S,3S)
-
(2R)
(2S,3S)
(2S,3S)
(2S,3S)
(2R)
3b
4
5
6
7
8
3. Conclusions
9
Herein we have described the synthesis of a wide range of new
alkenyl b-D-galactopyranoside derivatives and their use as chiral
10
11
12
13
14
15
16
0
77
73
84
86
88
81
templates for the stereoselective transformation of the double
bond moiety. Their cyclopronation and epoxidation reactions took
place with high diastereoisomeric excesses, up to 100%. The des in
both reactions were found to depend on the presence of the OH
group at the 2-position of the unprotected sugar, which determines
the selective transfer of the reagent from one face to the double
bond. The excellent chemical and stereochemical yields obtained
(2S,3S)
a
Yields refer to compounds obtained in each reaction after isolation and
purification.
b
Determined by relative integration in the 1H NMR spectra of reaction mixture.
Deduced by comparative studies of NMR data, Table 3.
c
allow us to consider the D-galactose moiety as an effective chiral

86
J. M. Vega-Pérez et al. / Tetrahedron: Asymmetry 21 (2010) 81–95
R1
O
Ph
O
O
O
O
R3
Ph
O
O
O
O
O
HO
BnO
NHAc
R2
NHAc
52
48 R1 = H , R2 = H, R3 = Ph
49 R1 = H , R2 = H, R3 = Me
50 R1 = H, R2 = Me, R3 = Me
51 R1 = Me , R2 = H, R3 = H
Scheme 8. Alkenyl glucopyranosides previously described.19
auxiliary; this methodology as an attractive way to obtain new chi-
ral cycloalkyl and epoxyalkyl b- -galactopyranoside derivatives
that can be employed as precursors of glycolipid analogues.
1Ph), 5.94 (m, OCH2CH@CH2), 5.53 (s, 1H, PhCH), 5.25 (m, 2H,
OCH2CH@CH2), 4.42 (ddd, 1H, Jgem 12.6 Hz, J 5.3 Hz, 4J 1.5 Hz,
OCHAHBCH@CH2), 4.31 (m, 2H, H-6e, H-1), 4.19 (dd, 1H, J3,4
3.7 Hz, J4,5 1.0 Hz, H-4), 4.12 (ddd, 1H, Jgem 12.5 Hz, J 6.9 Hz, 4J
1.1 Hz, OCHAHBCH@CH2), 4.06 (dd, 1H, J5,6a 1.9 Hz, J6e,6a 12.5 Hz,
H-6a), 3.77 (dd, 1H, J1,2 7.7 Hz, J2,3 9.5 Hz, H-2), 3.67 (dd, 1H, J2,3
9.5 Hz, J3,4 3.7 Hz, H-3), 3.45 (m, 1H, H-5), 2.52 (m, 2H, 2OH).
D
4. Experimental
4.1. General
4.2.2. (E)-3-Phenyl-2-propenyl 4,6-O-(S)-benzylidene-b-D-galac-
topyranoside 3
The solid was purified by column chromatography using hex-
ane–ethyl acetate (1:4) as eluent. Yield 1.2 g (92%); mp 185–
Evaporations were conducted under reduced pressure. Prepara-
tive chromatography was performed on Silica Gel 60 (E. Merck).
Kieselgel 60 F254 (E. Merck) was used for TLC. Melting points were
obtained on a Stuart Melting Point Apparatus SMP 10 and are
uncorrected. Optical rotations were obtained on a Perkin Elmer
Polarimeter Model 341 at 25 °C. Mass spectra were recorded on a
Micromass AUTOSPECQ mass spectrometer: EI at 70 eV and CI at
150 eV, HR mass measurements with resolutions of 10,000. FAB
mass spectra were recorded using a thioglycerol matrix. NMR spec-
tra were recorded at 25 °C on a Bruker AMX500 spectrometer and
on a Bruker AV500 spectrometer at 500 MHz for 1H and 125 MHz
for 13C. The chemical shifts are reported in ppm on the d scale rel-
ative to TMS. COSY, HSQC and NOESY experiments were performed
to assign the signals in the NMR spectra.
186 °C;
[a
]D = ꢀ22.8 (c 0.5, CH2Cl2); MS (CI): m/z 385 (5%)
[M+H]+. 1H NMR (500 MHz, CDCl3): d 7.6–7.2 (m, 10H, 2Ph), 6.65
(d, 1H, Jtrans 16.0 Hz, OCH2CH@CHPh), 6.34 (ddd, 1H, Jtrans 16.0 Hz,
J 5.8 Hz, J 6.8 Hz, OCH2CH@CHPh), 5.57 (s, 1H, PhCH), 4.61 (ddd,
1H, Jgem 12.5 Hz, J 5.8 Hz, 4J 1.5 Hz, OCHAHBCH@CHPh), 4.41 (d,
1H, J1,2 7.7 Hz, H-1), 4.37 (dd, 1H, J5,6e 1.5 Hz, J6e,6a 12.5 Hz, H-6e),
4.32 (ddd, 1H, Jgem 12.5 Hz, J 6.9 Hz, 4J 1.3 Hz, OCHAHBCH@CHPh),
4.22 (dd, 1H, J3,4 3.9 Hz, J4,5 1.1 Hz, H-4), 4.10 (dd, 1H, J5,6a 1.9 Hz,
J6e,6a 12.5 Hz, H-6a), 3.82 (dd, 1H, J1,2 7.7 Hz, J2,3 9.6 Hz, H-2), 3.71
(m, 1H, H-3), 3.50 (m, 1H, H-5), 2.52 (m, 2H, 2OH). 13C NMR
(125 MHz, CDCl3): d 137.5–126.4 (2Ph), 133.5 (OCH2CH@CHPh),
125.0 (OCH2CH@CHPh), 101.6 (C-1), 101.5 (PhCH), 75.3 (C-4),
72.8 (C-3), 71.9 (C-2), 69.9 (OCH2CH@CHPh), 69.2 (C-6), 66.8 (C-
5). HRMS (CI): [M+H]+, found 385.1641. C22H25O6 requires
385.1651. Anal. Calcd for C22H24O6: C, 68.74; H, 6.29. Found: C,
68.57; H, 6.41.
4.2. General procedure for the synthesis of alkenyl glycosides
2–8
To a solution of 2,3,4,6-tetra-O-acetyl-a-D-galactopyranosyl bro-
mide 1 (2.06 g, 5.0 mmol) in nitromethane–toluene (1:1) (30 mL),
4 Å molecular sieves (5 g), mercury cyanide (2.54 g, 10.0 mmol)
and the corresponding unsaturated alcohol (10.0 mmol) were
added. The mixture was heated at 50 °C with stirring until TLC
showed that all the starting material had reacted (2–3 h). The solid
was filtered through Celite and washed with dichloromethane. The
organic layer was washed with an aqueous saturated solution of so-
dium bicarbonate and brine, then dried (MgSO4), evaporated to dry-
ness and purified by column chromatography. To a solution of the
4.2.3. (E)-2-Butenyl 4,6-O-(S)-benzylidene-b-D-galactopyranoside 4
The solid was purified by column chromatography using hex-
ane–ethyl acetate (1:4) as eluent. Yield 1.4 g (87%); mp 178–
180 °C; [
a]
D = ꢀ43.1 (c 1.0, CH2Cl2); MS (FAB): m/z 345 (100%)
[M+Na]+. 1H NMR (500 MHz, CDCl3): d 7.5–7.3 (m, 5H, Ph), 5.77
(m, 1H, OCH2CH@CHCH3), 5.63 (m, 1H, OCH2CH@CHCH3), 5.56 (s,
1H, PhCH), 4.4–4.3 (m, 3H, OCHAHBCH@CHCH3, H-1, H-6e), 4.21
(dd, 1H, J3,4 3.8 Hz, J4,5 1.0 Hz, H-4), 4.1–4.0 (m, 2H, H-6a,
OCHAHBCH@CHCH3), 3.78 (dd, 1H, J1,2 7.7 Hz, J2,3 9.6 Hz, H-2),
3.70 (m, 1H, H-3), 3.48 (m, 1H, H-5), 2.50 (m, 2H, 2OH), 1.73 (dd,
3H, J 6.5 Hz, 4J 1.1 Hz, OCH2CH@CHCH3). 13C NMR (125 MHz,
CDCl3): d 137.4, 129.2, 128.2, 126.4 (Ph), 130.8 (OCH2CH@CHCH3),
126.6 (OCH2CH@CHCH3), 101.5 (PhCH), 101.4 (C-1), 75.3 (C-4),
72.8 (C-3), 71.8 (C-2), 70.0 (OCH2CH@CHCH3), 69.2 (C-6), 66.7 (C-
5), 17.8 (OCH2CH@CHCH3). HRMS (FAB): [M+Na]+, found
345.1297. C17H22O6Na requires 345.1314. Anal. Calcd for
C17H22O6: C, 63.34; H, 6.88. Found: C, 63.41; H, 6.74.
corresponding alkenyl 2,3,4,6-tetra-O-acetyl-b-D-galactopyrano-
side in methanol (50 mL), a solution of sodium methoxide (1 mmol)
in methanol (5 mL) was added. After 30 min at room temperature,
the solution was neutralised by the addition of Dowex 50 resin (H+
form), filtered and evaporated to dryness. To a solution of the corre-
sponding alkenyl b-D-galactopyranoside in acetonitrile (30 mL),
benzaldehyde dimethylacetal (10.0 mmol) and camphorsulfonic
acid (10 mg) were added. The mixture was stirred at room temper-
ature until TLC showed that all the starting material had reacted.
Then, triethylamine was added until pH 7. The reaction mixture
was evaporated and the compound obtained was purified by column
chromatography to give compounds 2–9 in good yields.
4.2.4. (E)-2-Decenyl 4,6-O-(S)-benzylidene-b-D-galactopyranoside 5
The solid was purified by column chromatographyusing hexane–
4.2.1. Allyl 4,6-O-(S)-benzylidene-b-D
-galactopyranoside 227
The solid was purified by column chromatography using hex-
ane–ethyl acetate (1:4) as eluent. Yield 1.1 g (72.2%). MS (CI): m/
z 309 (40%) [M+H]+. 1H NMR (500 MHz, CDCl3): d 7.5–7.3 (m, 5H,
ethyl acetate (1:2) as eluent. Yield 2.4 g (87%); mp 164–165 °C;
[a]
D = ꢀ14.6 (c 1.0, CH2Cl2); MS (CI): m/z 407 (5%) [M+H]+. 1H NMR
(500 MHz, CDCl3): d 7.6–7.3 (m, 5H, Ph), 5.74 [m, 1H, OCH2-
CH@CH(CH2)6CH3], 5.60 [m, 1H, OCH2CH@CH(CH2)6CH3], 5.55 (s,

J. M. Vega-Pérez et al. / Tetrahedron: Asymmetry 21 (2010) 81–95
87
Table 3
Comparative analysis of NMR data (d, ppm) in CDCl3 for the oxirane carbons and anomeric proton and carbon in compounds 32–47 versus 48–52
R1
O
O
R3
1'
2'
Sugar
3'
R2
Entry
Product
C-10 minor/major
C-20 minor/major
C-30 minor/major
H-1 minor/major
C-1 major/minor
Major oxirane configuration
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
32a
33
34
35
36
37
38
39
69.0
68.7/68.2
68.6
68.8
68.0
71.0
71.5/71.3
70.5
69.2
72.0
68.9
68.1
68.5
68.7
70.9
71.3
68.8/68.3
69.0/68.8
67.8
50.7
60.5
57.9/57.7
56.9/56.7
61.7
44.6
56.2/55.9
52.2
4.4–4.5
103.2
103.3/102.6
103.1
103.3/102.3
102.7
103.6
(2R)
4.46/4.39
4.40/4.35
4.41/4.33
4.33/4.25
4.40/4.35
4.49/4.40
4.49/4.44
4.56/4.51
4.49/4.44
4.43/4.38
4.50/4.44
4.42/4.35
4.43/4.35
4.43/4.34
4.51/4.43
4.59/4.55
4.68/4.49
4.75/4.67
4.67/4.44
4.96/4.90
(2S,3S)
(2S,3S)
(2S,3S)
(2S)
(2R)
(2S,3S)
(2R)
(2S,3S)
-
(2R)
(2S,3S)
(2S,3S)
(2S,3S)
(2R)
(2S,3S)
(2S,3S)
(2S,3S)
(2S)
56.3/56.0
58.3/57.9
51.3
60.7/60.4
44.6/44.3
56.3/56.0
51.7/51.6
44.6
56.2
62.8
103.7
50.8/50.6
61.4/60.8
55.8
50.7/50.5
61.2/61.0
57.7
56.8
56.2
62.7
60.3/60.1
56.9/56.7
60.5
57.1
50.8/50.3
103.7/103.4
103.8/103.6
103.5/103.2
103.3/103.1
103.5/103.2
103.5
40
41b
42
43
44
45
46
56.2/56.0
52.4
56.4
103.5
103.7
51.4
47
61.2/60.4
55.3/54.9
51.3/51.2
57.3/57.2
49.6
103.9/103.6
102.1/101.9
101.7/101.6
101.7/101.3
102.9/102.8
101.0/100.7
48c
49c
50c
51c
52c
69.5
70.8/68.9
(2R)
(2R)
44.2
a
b
c
Only one stereoisomer obtained.
No de.
Ref. 19.
1H, PhCH), 4.39 [dd, 1H, Jgem 11.7 Hz, J 6.0 Hz, OCHAHBCH@
CH(CH2)6CH3], 4.35–4.30 (m, 2H, H-1, H-6e), 4.21 (d, 1H, J3,4
3.7 Hz, H-4), 4.10–4.05 [m, 2H, H-6a, OCHAHBCH@CH(CH2)6CH3],
3.77 (dd, 1H, J1,2 7.7 Hz, J2,3 9.5 Hz, H-2), 3.69 (m, 1H, H-3), 3.47
(m, 1H, H-5), 2.52 (m, 2H, 2OH), 2.05 [m, 2H, OCH2CH@CHCH2-
(CH2)5CH3], 1.40–1.25 [m, 10H, OCH2CH@CHCH2(CH2)5CH3], 0.88
[t, 3H, J 6.9 Hz, OCH2CH@CH(CH2)6CH3]. 13C NMR (125 MHz, CDCl3):
d 137.4, 129.2, 128.2, 126.4 (Ph), 136.2 [OCH2CH@CH(CH2)6CH3],
125.1 [OCH2CH@CH(CH2)6CH3], 101.5 (PhCH), 101.4 (C-1), 75.3 (C-
4), 72.7 (C-3), 71.8 (C-2), 70.1 [OCH2CH@CH(CH2)6CH3], 69.2 (C-6),
66.7 (C-5), 32.3, 31.8, 29.2, 29.1, 29.0, 22.6 [OCH2CH@CH(CH2)6CH3],
14.1 [OCH2CH@CH(CH2)6CH3]. HRMS (CI): [M+H]+, found 407.2413.
C23H35O6 requires 407.2434. Anal. Calcd for C23H34O6: C, 67.96; H,
8.43. Found: C, 67.91; H, 8.14.
[M+Na]+, found 358.1375. C18H24O6Na requires 358.1392. Anal.
Calcd for C18H24O6: C, 64.27; H, 7.19. Found: C, 64.34; H, 7.27.
4.2.6. 2-Methyl-2-propenyl 4,6-O-(S)-benzylidene-b-D-
galactopyranoside 7
The compound was purified by column chromatography using
hexane–ethyl acetate (1:4) as eluent to obtain a syrup. Yield 1.1 g
(70%); [
a
]
D = ꢀ21.6 (c 0.8, CH2Cl2); MS (CI): m/z 323 (5%) [M+H]+.
1H NMR (500 MHz, CDCl3): d 7.5–7.3 (m, 5H, Ph), 5.55 (s, 1H, PhCH),
5.03, 4.94 [2 m, 2H, OCH2C(CH3)@CH2], 4.4–4.3 [m, 3H, H-1, H-6e,
OCHAHBC(CH3)@CH2], 4.21 (dd, 1H, J3,4 3.8 Hz, J4,5 0.8 Hz, H-4),
4.10–4.05 [m, 2H, H-6a, OCHAHBC(CH3)@CH2], 3.80 (dd, 1H, J1,2
7.8 Hz, J2,3 9.6 Hz, H-2), 3.70 (dd, 1H, J2,3 9.6 Hz, J3,4 3.8 Hz, H-3),
3.46 (m, 1H, H-5), 2.60 (m, 2H, 2OH), 1.77 [s, 3H, OCH2C(CH3)@CH2].
13C NMR (125 MHz, CDCl3): d 141.2 [OCH2C(CH3)@CH2], 137.5,
129.2, 128.2, 126.4 (Ph), 113.3 [OCH2C(CH3)@CH2], 101.4 (PhCH),
101.3 (C-1), 75.3 (C-4), 72.7 [C-3, OCH2C(CH3)@CH2], 71.8 (C-2),
69.1 (C-6), 66.7 (C-5), 19.6 [OCH2C(CH3)@CH2]. HRMS (CI): [M+H]+,
found 323.241457. C17H23O6 requires 323.243364.
4.2.5. 3-Methyl-2-butenyl 4,6-O-(S)-benzylidene-b-D-
galactopyranoside 6
The solid was purified by column chromatography using hexane–
ethyl acetate (1:4) as eluent. Yield 1.85 g (86%); mp 177–178 °C;
[
a]
D = ꢀ26.5 (c 1.0, CH2Cl2); MS (FAB): m/z 358 (65%) [M+Na]+. 1H
NMR (500 MHz, CDCl3): d 7.5–7.3 (m, 5H, Ph), 5.56 (s, 1H, PhCH),
5.38 [m, 1H, OCH2CH@C(CH3)2], 4.40 [dd, Jgem 11.7 Hz, J 6.4 Hz,
OCHAHBCH@C(CH3)2], 4.35 (dd, 1H, J5,6e 1.2 Hz, J6e,6a 12.5 Hz, H-6e),
4.32 (d, 1H, J1,2 7.5 Hz, H-1), 4.22–4.17 [m, 2H, H-4, OCHAHBCH@
C(CH3)2], 4.09 (dd, 1H, J5,6a 1.8 Hz, J6e,6a 12.5 Hz, H-6a), 3.80 (dd,
1H, J1,2 7.8 Hz, J2,3 9.5 Hz, H-2), 3.70 (m, 1H, H-3), 3.47 (m, 1H, H-
5), 2.51 (m, 2H, 2OH), 1.77, 1.69 [2s, 6H, OCH2CH@C(CH3)2]. 13C
NMR (125 MHz, CDCl3): d 138.3 [OCH2CH@C(CH3)2], 137.5, 129.2,
128.2, 126.4 (Ph), 120.0 [OCH2CH@C(CH3)2], 101.5 (PhCH), 101.3
(C-1), 75.3 (C-4), 72.8 (C-3), 71.8 (C-2), 69.2 (C-6), 66.7 (C-5), 65.5
[OCH2CH@C(CH3)2], 25.8, 18.0 [OCH2CH@C(CH3)2]. HRMS (FAB):
4.2.7. (E)-2-Methyl-3-phenyl-2-propenyl 4,6-O-(S)-benzylidene-
b-D
-galactopyranoside 8
The compound was purified by column chromatography using
hexane–ethyl acetate (1:3) as eluent to obtain a syrup. Yield
1.11 g (74%); [
a
]
D = ꢀ27.4 (c 1.0, CH2Cl2); MS (EI): m/z 398 (3%)
[M]+Å. 1H NMR (500 MHz, CDCl3): d 7.6–7.2 (m, 10H, 2Ph), 6.56 [s,
1H, OCH2C(CH3)@CHPh], 5.56 (s, 1H, PhCH), 4.46 [d, 1H, Jgem 12.
Hz, OCHAHBC(CH3)@CHPh], 4.4–4.3 (m, 2H, H-1, H-6e), 4.25–4.20
[m, 2H, H-4, OCHAHBC(CH3)@CHPh], 4.09 (d, 1H, J6e,6a 12.5 Hz, H-
6a), 3.83 (m, 1H, H-2), 3.71 (m, 1H, H-3), 3.470 (m, 1H, H-5), 2.67
(m, 2H, 2OH), 1.95 [s, 3H, OCH2C(CH3)@CHPh]. 13C NMR

88
J. M. Vega-Pérez et al. / Tetrahedron: Asymmetry 21 (2010) 81–95
(125 MHz, CDCl3): d 137.5–126.4 [2Ph, OCH2C(CH3)@CHPh], 101.4
(PhCH), 101.3 (C-1), 75.3 [OCH2C(CH3)@CHPh], 75.2 (C-4), 72.7
(C-3), 71.8 (C-2), 69.1 (C-6), 66.7 (C-5), 15.7 [OCH2C(CH3)@CHPh].
HRMS (EI): [M]+Å, found 398.1738. C23H26O6 requires 398.1729.
3), 78.5 (C-2), 75.3 (2-PhCH2O), 74.1 (C-4), 72.1 (3-PhCH2O), 70.1
(OCH2CH@CHCH3), 69.3 (C-6), 66.4 (C-5), 17.8 (OCH2CH@CHCH3).
HRMS (FAB): [M+Na]+, found 525.2248. C31H34O6Na requires
525.2253. Anal. Calcd for C31H34O6: C, 74.08; H, 6.82. Found: C,
73.83; H, 6.81.
4.3. Synthesis of 2,3-di-O-benzyl derivatives 9–15
4.3.4. (E)-2-Decenyl 2,3-di-O-benzyl-4,6-O-(S)-benzylidene-b-D-
To a cooled solution (5 °C) of sugar derivatives 2–8 (1.0 mmol)
in freshly distilled THF (20 mL) were added, successively, freshly
powdered potassium hydroxide (0.7 g, 8.33 mmol), 18-crown-6
(20–30 mg) and benzyl bromide (0.5 mL, 4.1 mmol). The reaction
mixture was stirred at this temperature for 3 h, left overnight at
room temperature, then diluted with dichloromethane (30 mL)
and washed successively with water and an aqueous saturated
solution of sodium bicarbonate, dried (MgSO4), filtered and the fil-
trate was evaporated to dryness.
galactopyranoside 12
The solid was purified by column chromatographyusing hexane–
ethyl acetate (3:1) as eluent. Yield 0.5 g (85%); mp 181–182 °C;
[a]
D = +20.1 (c 1.0, CH2Cl2); MS (FAB): m/z 609 (10%) [M+Na]+. 1H
NMR (500 MHz, CDCl3): d 7.60–7.25 (m, 15H, 3Ph), 5.74 [m, 1H,
OCH2CH@CH(CH2)6CH3], 5.60 [m, 1H, OCH2CH@CH(CH2)6CH3],
5.50 (s, 1H, PhCH), 4.95 (d, 1H, Jgem 10.9 Hz, 2-PhCHAHBO), 4.80–
4.70 (m, 3H, 2-PhCHAHBO, 3-PhCH2O), 4.44 (d, 1H, J1,2 7.8 Hz, H-1),
4.40 [dd, 1H, Jgem 12.0 Hz, J 5.8 Hz, OCHAHBCH@CH(CH2)6CH3],
4.31 (dd, 1H, J5,6e 1.5 Hz, J6e,6a 12.3 Hz, H-6e), 4.11–4.07 [m, 2H, H-
4, OCHAHBCH@CH(CH2)6CH3], 4.01 (dd, 1H, J5,6a 1.8 Hz, J6e,6a
12.3 Hz, H-6a), 3.87 (dd, 1H, J1,2 7.8 Hz, J2,3 9.7 Hz, H-2), 3.56 (dd,
1H, J2,3 9.7 Hz, J3,4 3.7 Hz, H-3), 3.30 (m, 1H, H-5), 2.04 [m, 2H,
OCH2CH@CHCH2(CH2)5CH3], 1.40–1.20 [m, 10H, OCH2CH@CHCH2-
(CH2)5CH3], 0.88 [t, 3H, J 7.0 Hz, OCH2CH@CH(CH2)6CH3]. 13C NMR
(125 MHz, CDCl3): d 139.0–126.5 (3Ph), 135.0 [OCH2CH@CH(CH2)6-
CH3], 125.7 [OCH2CH@CH(CH2)6CH3], 102.6 (C-1), 101.4 (PhCH),
79.3 (C-3), 78.5 (C-2), 75.2 (2-PhCH2O), 74.1 (C-4), 72.1 (3-PhCH2O),
70.2 [OCH2CH@CH(CH2)6CH3], 69.3 (C-6), 66.4 (C-5), 32.3, 31.8, 29.2,
29.1, 22.6 [OCH2CH@CH(CH2)6CH3], 14.1 [OCH2CH@CH(CH2)6CH3].
HRMS (FAB): [M+Na]+, found 609.3224. C37H46O6Na requires
609.3192. Anal. Calcd for C37H46O6: C, 75.74; H, 7.90. Found: C,
75.89; H, 7.90.
4.3.1. Allyl 2,3-di-O-benzyl-4,6-O-(S)-benzylidene-b-D-
galactopyranoside 927
The compound was purified by column chromatography using
hexane–ethyl acetate (3:1) as eluent to obtain a syrup. Yield
0.3 g (77%); 1H NMR (500 MHz, CDCl3): d 7.6–7.3 (m, 15H, 3Ph),
5.95 (m, 1H, OCH2CH@CH2), 5.48 (s, 1H, PhCH), 5.32 (m, 2H,
OCH2CH@CH2), 4.85 (m, 4H, 2-PhCH2O, 3-PhCH2O), 4.44 (m, 2H,
OCHAHBCH@CH2, H-1), 4.29 (dd, 1H, J5,6e 1.5 Hz, J6e,6a 12.3 Hz, H-
6e), (ddd, 1H, Jgem 12.9 Hz, J 5.9 Hz, 4J 1.3 Hz, OCHAHBCH@CH2),
4.09 (dd, 1H, J3,4 3.7 Hz, J4,5 1.0 Hz, H-4), 4.00 (dd, 1H, J5,6a 1.8 Hz,
J6e,6a 12.3 Hz, H-6a), 3.86 (dd, 1H, J1,2 7.8 Hz, J2,3 9.6 Hz, H-2), 3.54
(dd, 1H, J2,3 9.6 Hz, J3,4 3.7 Hz, H-3), 3.30 (m, 1H, H-5).
4.3.2. (E)-3-Phenyl-2-propenyl 2,3-di-O-benzyl-4,6-O-(S)-
benzylidene-b-
D-galactopyranoside 10
4.3.5. 3-Methyl-2-butenyl 2,3-di-O-benzyl-4,6-O-(S)-
The compound was purified by column chromatography using
hexane–ethyl acetate (3:1) as eluent to obtain a syrup. Yield
benzylidene-b-D-galactopyranoside 13
The solid was purified by column chromatography using hex-
ane–ethyl acetate (3:1) as eluent. Yield 0.4 g (74%); mp 177–
0.4 g (77%); [
a]
D = ꢀ30.3 (c 0.4, CH2Cl2); MS (FAB): m/z 587 (82%)
[M+Na]+. 1H NMR (500 MHz, CDCl3): d 7.6–7.2 (m, 20H, 4Ph),
6.65 (d, 1H, Jtrans 16.0 Hz, OCH2CH@CHPh), 6.31 (dt, 1H, Jtrans
16.0 Hz, J 5.9 Hz, OCH2CH@CHPh), 5.51 (s, 1H, PhCH), 4.97, 4.84
(2d, 2H, Jgem 10.9 Hz, 2-PhCH2O), 4.79, 4.75 (2d, 2H, Jgem 12.4 Hz,
3-PhCH2O), 4.60 (dd, 1H, Jgem 13.0 Hz, J 5.8 Hz, OCHAHBCH@CHPh),
4.51 (d, 1H, J1,2 7.8 Hz, H-1), 4.35–4.30 (m, 2H, OCHAHBCH@CHPh,
H-6e), 4.12 (d, 1H, J3,4 3.5 Hz, H-4), 4.03 (dd, 1H, J5,6a 1.7 Hz, J6e,6a
12.3 Hz, H-6a), 3.91 (dd, 1H, J1,2 7.8 Hz, J2,3 9.7 Hz, H-2), 3.58 (dd,
1H, J2,3 9.7 Hz, J3,4 3.6 Hz, H-3), 3.33 (m, 1H, H-5). 13C NMR
(125 MHz, CDCl3): d 139.0–126.5 (4Ph), 132.5 (OCH2CH@CHPh),
125.6 (OCH2CH@CHPh), 102.6 (C-1), 101.4 (PhCH), 79.3 (C-3),
78.5 (C-2), 75.3 (2-PhCH2O), 74.0 (C-4), 72.1 (3-PhCH2O), 69.8
(OCH2CH@CHPh), 69.3 (C-6), 66.5 (C-5). HRMS (FAB): [M+Na]+,
found 587.2382. C36H35O6Na requires 587.2410.
178 °C; [
a
]
D = ꢀ50.3 (c 1.0, CH2Cl2); MS (FAB): m/z 539 (5%)
[M+Na]+. 1H NMR (500 MHz, CDCl3): d 7.6–7.2 (m, 15H, 3Ph),
5.50 (s, 1H, PhCH), 5.41 [m, 1H, OCH2CH@C(CH3)2], 4.95 (d, 1H, Jgem
10.8 Hz, 2-PhCHAHBO), 4.80–4.73 (m, 3H, 2-PhCHAHBO, 3-PhCH2O),
4.45 (d, 1H, J1,2 7.8 Hz, H-1), 4.40 [dd, Jgem 11.8 Hz, J 6.5 Hz,
OCHAHBCH@C(CH3)2], 4.31 (dd, 1H, J5,6e 1.5 Hz, J6e,6a 12.2 Hz, H-
6e), 4.21 [dd, Jgem 11.8 Hz, J 7.4 Hz, OCHAHBCH@C(CH3)2], 4.10
(dd, 1H, J3,4 3.7 Hz, J4,5 0.7 Hz, H-4), 4.02 (dd, 1H, J5,6a 1.8 Hz, J6e,6a
12.2 Hz, H-6a), 3.86 (dd, 1H, J1,2 7.8 Hz, J2,3 9.7 Hz, H-2), 3.56 (dd,
1H, J2,3 9.7 Hz, J3,4 3.7 Hz, H-3), 3.30 (m, 1H, H-5), 1.76, 1.68 [2s,
6H, OCH2CH@C(CH3)2]. 13C NMR (125 MHz, CDCl3):
d 139.0
[OCH2CH@C(CH3)2], 138.6–126.6 (3Ph), 120.7 [OCH2CH@C(CH3)2],
102.4 (C-1), 101.4 (PhCH), 79.4 (C-3), 78.5 (C-2), 75.2 (2-PhCH2O),
74.1 (C-4), 72.1 (3-PhCH2O), 69.3 (C-6), 66.4 (C-5), 65.7
[OCH2CH@C(CH3)2], 25.8, 18.0 [OCH2CH@C(CH3)2]. HRMS (FAB):
[M+Na]+, found 539.2416. C32H36O6 requires 539.2410. Anal. Calcd
for C32H36O6Na: C, 74.39; H, 7.02. Found: C, 74.57; H, 7.21.
4.3.3. (E)-2-Butenyl 2,3-di-O-benzyl-4,6-O-(S)-benzylidene-b-D-
galactopyranoside 11
The solid was purified by column chromatography using hex-
ane–ethyl acetate (3:1) as eluent. Yield 0.4 g (85%); mp 135–
4.3.6. 2-Methyl-2-propenyl 2,3-di-O-benzyl-4,6-O-(S)-
136 °C; [
a
]D = +16.0 (c 1.0, CH2Cl2); MS (FAB): m/z 525 (10%)
benzylidene-b-D-galactopyranoside 14
[M+Na]+. 1H NMR (500 MHz, CDCl3): d 7.60–7.25 (m, 15H, 3Ph),
5.76 (m, 1H, OCH2CH@CHCH3), 5.63 (m, 1H, OCH2CH@CHCH3),
5.50 (s, 1H, PhCH), 4.95 (d, 1H, Jgem 10.8 Hz, 2-PhCHAHBO), 4.80–
4.70 (m, 3H, 2-PhCHAHBO, 3-PhCH2O), 4.44 (d, 1H, J1,2 7.8 Hz, H-
1), 4.38 (dd, 1H, Jgem 11.9 Hz, J 5.9 Hz, OCHAHBCH@CHCH3), 4.31
(dd, 1H, J5,6e 1.3 Hz, J6e,6a 12.3 Hz, H-6e), 4.11–4.06 (m, 2H, H-4,
OCHAHBCH@CHCH3), 4.01 (dd, 1H, J5,6a 1.6 Hz, J6e,6a 12.3 Hz, H-
6a), 3.86 (dd, 1H, J1,2 7.9 Hz, J2,3 9.6 Hz, H-2), 3.56 (dd, 1H, J2,3
9.7 Hz, J3,4 3.7 Hz, H-3), 3.31 (m, 1H, H-5), 1.71 (dd, 3H, J 6.4 Hz,
4J 1.0 Hz, OCH2CH@CHCH3). 13C NMR (125 MHz, CDCl3): d 139.0–
126.6 (3Ph, OCH2CH@CHCH3), 102.5 (C-1), 101.4 (PhCH), 79.3 (C-
The solid was purified by column chromatography using hex-
ane–ethyl acetate (3:1) as eluent. Yield 0.3 g (58%); mp 140–
141 °C; [a]
D = +36.3 (c 0.9, CH2Cl2); MS (CI): m/z 503 (2%) [M+H]+.
1H NMR (500 MHz, CDCl3): d 7.6–7.3 (m, 15H, 3Ph), 5.50 (s, 1H,
PhCH), 5.05, 4.91 [2 m, 2H, OCH2C(CH3)@CH2], 4.96 (d, 1H, Jgem
10.8 Hz, 2-PhCHAHBO), 4.80–4.73 (m, 3H, 2-PhCHAHBO, 3-PhCH2O),
4.43 (d, 1H, J1,2 7.8 Hz, H-1), 4.34 [d, Jgem 12.7 Hz, OCHA-
HBC(CH3)@CH2], 4.31 (dd, 1H, J5,6e 1.5 Hz, J6e,6a 12.3 Hz, H-6e),
4.11 (dd, 1H, J3,4 3.7 Hz, J4,5 0.8 Hz, H-4), 4.06 [d 1H, Jgem 12.7 Hz,
OCHAHBC(CH3)@CH2], 4.02 (dd, 1H, J5,6a 1.8 Hz, J6e,6a 12.3 Hz, H-
6a), 3.89 (dd, 1H, J1,2 7.8 Hz, J2,3 9.7 Hz, H-2), 3.57 (dd, 1H, J2,3

J. M. Vega-Pérez et al. / Tetrahedron: Asymmetry 21 (2010) 81–95
89
9.7 Hz, J3,4 3.7 Hz, H-3), 3.31 (m, 1H, H-5), 1.78 [s, 3H, OCH2-
C(CH3)@CH2]. 13C NMR (125 MHz, CDCl3): d 141.5 [OCH2C(CH3)@
CH2], 138.8–126.5 (3Ph), 112.7 [OCH2C(CH3)@CH2], 102.3 (C-1),
101.3 (PhCH), 79.4 (C-3), 78.5 (C-2), 75.3 (2-PhCH2O), 74.0 (C-4),
72.7 [OCH2C(CH3)@CH2], 72.1 (3-PhCH2O), 69.3 (C-6), 66.4 (C-5),
19.6 [OCH2C(CH3)@CH2]. HRMS (CI): [M+H]+, found 503.2414.
C31H35O6 requires 503.2433. Anal. Calcd for C31H34O6: C, 74.08;
H, 6.82. Found: C, 74.13; H, 6.65.
5.7 Hz, J 6.9 Hz, OCH2CH@CHPh), 5.47 (s, 1H, PhCH), 4.78, 4.74
(2d, 2H, Jgem 12.4 Hz, PhCH2O), 4.59 (ddd, 1H, Jgem 13.0 Hz, J
5.8 Hz, 4J 1.5 Hz, OCHAHBCH@CHPh), 4.42 (d, 1H, J1,2 7.8 Hz, H-1),
4.35–4.30 (m, 2H, H-6e, OCHAHBCH@CHPh), 4.14 (dd, 1H, J3,4
3.6 Hz, J4,5 1.0 Hz, H-4), 4.1–4.0 (m, 2H, H-2, H-6a), 3.51 (dd, 1H,
J2,3 9.7 Hz, J3,4 3.6 Hz, H-3), 3.37 (m, 1H, H-5). 13C NMR
(125 MHz, CDCl3): d 138.1–126.4 (3Ph), 133.3 (OCH2CH@CHPh),
125.2 (OCH2CH@CHPh), 101.7 (C-1), 101.2 (PhCH), 79.3 (C-3),
73.2 (C-4), 71.6 (PhCH2O), 70.1 (C-2), 69.6 (OCH2CH@CHPh), 69.3
(C-6), 66.7 (C-5). HRMS (CI): [M+H]+, found 475.2072. C29H31O6 re-
quires 475.2121.
4.3.7. (E)-2-Methyl-3-phenyl-2-propenyl 2,3-di-O-benzyl-4,6-O-
(S)-benzylidene-b-
The solid was purified by column chromatography using hex-
ane–ethyl acetate (3:1) as eluent. Yield 0.5 g (74%); [
D = ꢀ27.4
(c 1.0, CH2Cl2); MS (FAB): m/z 601 (60%) [M+Na]+. 1H NMR
(500 MHz, CDCl3): 7.6–7.2 (m, 20H, 4Ph), 6.58 [s, 1H,
D-galactopyranoside 15
a
]
4.4.3. (E)-2-Butenyl 3-O-benzyl-4,6-O-(S)-benzylidene-b-D-
galactopyranoside 18
The solid was purified by column chromatography using hex-
ane–ethyl acetate (2:1) as eluent. Yield (calculated from the
amount of starting material transformed) 0.2 g (35%); mp 153–
d
OCH2C(CH3)@CHPh], 5.51 (s, 1H, PhCH), 4.99 (d, 1H, Jgem 10.8 Hz,
2-PhCHAHBO), 4.84 (d, 1H, Jgem 10.8 Hz, 2-PhCHAHBO), 4.79 (d,
1H, Jgem 12.4 Hz, 3-PhCHAHBO), 4.76 (d, 1H, Jgem 12.4 Hz, 3-
PhCHAHBO), 4.50–4.45 [m, 2H, H-1, OCHAHBC(CH3)@CHPh], 4.34
(dd, 1H, J5,6e 0.8 Hz, J6e,6a 12.3 Hz, H-6e), 4.22 [d, 1H, Jgem 12.4 Hz,
OCHAHBC(CH3)@CHPh], 4.13 (d, 1H, J3,4 3.5 Hz, H-4), 4.04 (dd, 1H,
J5,6a 1.4 Hz, J6e,6a 12.3 Hz, H-6a), 3.93 (dd, 1H, J1,2 7.9 Hz, J2,3
9.6 Hz, H-2), 3.59 (dd, 1H, J2,3 9.7 Hz, J3,4 3.6 Hz, H-3), 3.34 (m,
1H, H-5), 1.94 [s, 3H, OCH2C(CH3)@CHPh]. 13C NMR (125 MHz,
CDCl3): d 138.8–126.4 [2Ph, OCH2C(CH3)@CHPh], 102.2 (PhCH),
101.3 (C-1), 79.4 (C-3), 78.5 (C-2), 75.4 (2-PhCH2O), 75.1
[OCH2C(CH3)@CHPh], 74.0 (C-4), 72.0 (3-PhCH2O), 69.2 (C-6),
66.4 (C-5), 15.7 [OCH2C(CH3)@CHPh]. HRMS (FAB): [M+Na]+, found
601.2532. C37H38O6 requires 601.2566. Anal. Calcd for C37H38O6: C,
76.79; H, 6.62. Found: C, 76.74; H, 6.59.
155 °C; [a]D = +8.2 (c 0.5, CH2Cl2); MS (FAB): m/z 435 (35%)
[M+Na]+. 1H NMR (500 MHz, CDCl3): d 7.55–7.25 (m, 10H, 2Ph),
5.75 (m, 1H, OCH2CH@CHCH3), 5.63 (m, 1H, OCH2CH@CHCH3),
5.46 (s, 1H, PhCH), 4.76 (m, 2H, PhCH2O), 4.4–4.3 (m, 2H,
OCHAHBCH@CHCH3, H-1), 4.31 (dd, 1H, J5,6e 1.5 Hz, J6e,6a 12.3 Hz,
H-6e), 4.13 (dd, 1H, J3,4 3.6 Hz, J4,5 0.9 Hz, H-4), 4.09–3.99 (m, 3H,
OCHAHBCH@CHCH3, H-2, H-6a), 3.50 (dd, 1H, J2,3 9.7 Hz, J3,4
3.6 Hz, H-3), 3.35 (m, 1H, H-5), 2.41 (d, 1H, J2,OH 1.8 Hz, OH), 1.72
(dd, 3H, J 6.4 Hz, 4J 1.2 Hz, OCH2CH@CHCH3). 13C NMR (125 MHz,
CDCl3):
d 138.2–126.4 (2Ph), 130.5 (OCH2CH@CHCH3), 126.8
(OCH2CH@CHCH3), 101.6 (C-1), 101.2 (PhCH), 79.2 (C-3), 73.3 (C-
4), 71.6 (PhCH2O), 70.1 (C-2), 69.7 (OCH2CH@CHCH3), 69.3 (C-6),
66.7 (C-5), 17.8 (OCH2CH@CHCH3). HRMS (FAB): [M+Na]+, found
435.1790. C24H28O6Na requires 435.1784. Anal. Calcd for
C24H28O6: C, 69.88; H, 6.84. Found: C, 69.57; H, 7.21.
4.4. Synthesis of 3-O-benzyl derivatives 16–22
To a cooled solution (5 °C) of sugar derivatives 2–8 (3.0 mmol)
in freshly distilled THF (20 mL) were added, successively, freshly
powdered potassium hydroxide (1.0 g, 11.9 mmol), 18-crown-6
(60 mg, 0.2 mmol) and benzyl bromide (0.4 mL, 3.4 mmol). The
reaction mixture was stirred at this temperature for 20 min, then
diluted with dichloromethane (30 mL) and washed successively
with water and an aqueous saturated solution of sodium bicarbon-
ate, dried (MgSO4), filtered and the filtrate was evaporated to
dryness.
4.4.4. (E)-2-Decenyl 3-O-benzyl-4,6-O-(S)-benzylidene-b-D-gala-
ctopyranoside 19
The solid was purified by column chromatographyusing hexane–
ethyl acetate (2:1) as eluent. Yield (calculated from the amount of
starting material transformed) 0.4 g (77%); mp 118–120 °C;
[a
]
D = ꢀ44.0 (c 0.3, CH2Cl2); MS (FAB): m/z 519 (85%) [M+Na]+. 1H
NMR (500 MHz, CDCl3): d 7.60–7.25 (m, 10H, 2Ph), 5.74 [m, 1H,
OCH2CH@CH(CH2)6CH3], 5.59 [m, 1H, OCH2CH@CH(CH2)6CH3],
5.46 (s, 1H, PhCH), 4.76 (s, 2H, PhCH2O), 4.40–4.35 [m, 2H, H-1,
OCHAHBCH@CH(CH2)6CH3], 4.30 (dd, 1H, J5,6e 1.2 Hz, J6e,6a 12.3 Hz,
H-6e), 4.13 (d, 1H, J3,4 3.5 Hz, H-4), 4.09–4.00 [m, 3H, H-2, H-6a,
OCHAHBCH@CH(CH2)6CH3], 3.50 (dd, 1H, J2,3 9.7 Hz, J3,4 3.6 Hz, H-
3), 3.34 (m, 1H, H-5), 2.45 (d, 1H, J2,OH 1.7 Hz, OH), 2.04 [m, 2H,
OCH2CH@CHCH2(CH2)5CH3], 1.40–1.20 [m, 10H, OCH2CH@
CHCH2(CH2)5CH3], 0.88 [t, 3H, J 6.9 Hz, OCH2CH@CH(CH2)6CH3].
13C NMR (125 MHz, CDCl3): d 138.1–126.4 (2Ph), 136.0 [OCH2-
CH@CH(CH2)6CH3], 125.2 [OCH2CH@CH(CH2)6CH3], 101.5 (C-1),
101.1 (PhCH), 79.2 (C-3), 73.2 (C-4), 71.5 (PhCH2O), 70.0
[OCH2CH@CH(CH2)6CH3], 69.9 (C-2), 69.3 (C-6), 66.6 (C-5), 32.3,
31.8, 29.2, 29.1, 29.0, 22.6 [OCH2CH@CH(CH2)6CH3], 14.1 [OCH2CH@
CH(CH2)6CH3]. HRMS (FAB): [M+Na]+, found 519.2713. C30H40O6Na
requires 519.2723. Anal. Calcd for C30H40O6: C, 72.55; H, 8.12.
Found: C, 72.80; H, 8.40.
4.4.1. Allyl 3-O-benzyl-4,6-O-(S)-benzylidene-b-D-galactopyran-
oside 1627
The compound was purified by column chromatography using
hexane–ethyl acetate (1.5:1) as eluent to obtain a syrup. Yield (cal-
culated from the amount of starting material transformed) 0.7 g
(88%); MS (FAB): m/z 421 (50%) [M+Na]+. 1H NMR (500 MHz,
CDCl3): d 7.5–7.3 (m, 10H, 2Ph), 5.94 (m, 1H, OCH2CH@CH2), 5.44
(s, 1H, PhCH), 5.24 (m, 2H, OCH2CH@CH2), 4.78, 4.74 (2 br s, 2H,
3-PhCH2O), 4.41 (ddd, 1H, Jgem 12.5 Hz,
J
5.3 Hz, 4J 1.5 Hz,
OCHAHBCH@CH2), 4.34 (d, 1H, J1,2 7.8 Hz, H-1), 4.29 (dd, 1H, J5,6e
1.5 Hz, J6e,6a 12.3 Hz, H-6e), 4.12 (m, 2H, OCHAHBCH@CH2, H-4),
4.01 (m, 2H, H-2, H-6a), 3.48 (dd, 1H, J2,3 9.7 Hz, J3,4 3.6 Hz, H-3),
3.34 (m, 1H, H-5). HRMS (FAB): [M+Na]+, found 421.1628.
C23H26O6Na requires 421.1627.
4.4.5. 3-Methyl-2-butenyl 3-O-benzyl-4,6-O-(S)-benzylidene-b-
4.4.2. (E)-3-Phenyl-2-propenyl 3-O-benzyl-4,6-O-(S)-benzy-
D-galactopyranoside 20
lidene-b-
D-galactopyranoside 17
The solid was purified by column chromatography using hex-
The compound was purified by column chromatography using
hexane–ethyl acetate (2:1) as eluent to obtain a syrup. Yield (cal-
culated from the amount of starting material transformed) 0.4 g
ane–ethyl acetate (1.5:1) as eluent. Yield (calculated from the
amount of starting material transformed) 0.3 g (66%); mp 188–
190 °C; [a]
D = +11.0 (c 1.0, CH2Cl2); MS (CI): m/z 427 (5%) [M+H]+.
(67%); [
a]
D = ꢀ35.1 (c 1.0, CH2Cl2); MS (CI): m/z 475 (2%) [M+H]+.
1H NMR (500 MHz, CDCl3): d 7.60–7.25 (m, 10H, 2Ph), 5.46 (s,
1H, PhCH), 5.39 [m, 1H, OCH2CH@C(CH3)2], 4.76 (s, 2H, PhCH2O),
4.38 [dd, Jgem 11.7 Hz, J 6.5 Hz, OCHAHBCH@C(CH3)2], 4.34–4.30
1H NMR (500 MHz, CDCl3): d 7.6–7.2 (m, 15H, 3Ph), 6.64 (d, 1H,
Jtrans 16.0 Hz, OCH2CH@CHPh), 6.33 (ddd, 1H, Jtrans 16.0 Hz, J

90
J. M. Vega-Pérez et al. / Tetrahedron: Asymmetry 21 (2010) 81–95
(m, 2H, H-1, H-6e), 4.20 [dd, Jgem 11.7 Hz,
J
7.8 Hz,
silica gel. The diastereomeric excess (de) was determined by 1H
NMR.
OCHAHBCH@C(CH3)2], 4.12 (dd, 1H, J3,4 3.6 Hz, J4,5 0.9 Hz, H-4),
4.05–3.00 (m, 2H, H-2, H-6a), 3.50 (dd, 1H, J2,3 9.7 Hz, J3,4 3.6 Hz,
H-3), 3.34 (m, 1H, H-5), 2.41 (d, 1H, J2,OH 1.9 Hz, OH), 1.76, 1.68
[2s, 6H, OCH2CH@C(CH3)2]. 13C NMR (125 MHz, CDCl3): d 138.8
[OCH2CH@C(CH3)2], 138.0–126.6 (2Ph), 120.2 [OCH2CH@C(CH3)2],
101.5 (C-1), 101.2 (PhCH), 79.2 (C-3), 73.3 (C-4), 71.6 (PhCH2O),
70.1 (C-2), 69.3 (C-6), 66.8 (C-5), 65.3 [OCH2CH@C(CH3)2], 25.8,
18.0 [OCH2CH@C(CH3)2]. HRMS (CI): [M+H]+, found 427.2098.
C25H31O6 requires 427.2121. Anal. Calcd for C25H30O6: C, 70.40;
H, 7.09. Found: C, 70.00; H, 6.86.
4.5.1. (2S,3S)-(2-Phenylcyclopropyl)methyl 4,6-O-(S)-benzyli-
dene-b-D-galactopyranoside 23
Two stereoisomers were obtained in a 3.7:1 ratio (57% de). The
pure diastereomeric mixture was obtained as a syrup by column
chromatography using dichlorometane–methanol (30:1) as eluent.
Yield 0.3 g (74%); [
a
]D = ꢀ22.1 (c 1.0, CH2Cl2); MS (FAB): m/z 421
(50%) [M+Na]+. 1H NMR (500 MHz, CDCl3): d 7.6–7.0 (m, 10H, 2Ph),
5.56 (s, 0.21H, PhCH minor), 5.54 (s, 0.79H, PhCH major), 4.38 (d,
1H, J1,2 7.8 Hz, H-1), 4.22–4.19 (m, 2H, H-4, H-6e), 4.02 (dd, 1H, J5,6a
1.6 Hz, J6e,6a 12.4 Hz, H-6a), 3.86 [dd, 1H Jgem 10.7 Hz, J 7.0 Hz,
OCHAHBCH(CH2)CHPh], 3.77 (m, 1H, H-2), 3.71 (m, 1H, H-3), 3.66
[dd, 1H, Jgem 10.8 Hz, J 6.7 Hz, OCHAHBCH(CH2)CHPh], 3.48 (m,
0.21H, H-5 minor), 3.43 (m, 0.79H, H-5 major), 2.49 (m, 2H, 2OH),
1.87 [m, 1H, OCH2CH(CH2)CHPh], 1.52 [m, 1H, OCH2CH(CH2)Ph],
1.01 [m, 1H, OCH2CH(CHAHB)CHPh], 0.95 [m, 1H, OCH2CH
(CHAHB)CHPh]. 13C NMR (125 MHz, CDCl3): d 142.4–125.6 (2Ph),
102.4 (C-1 major), 102.1 (C-1 minor), 101.4 (PhCH), 75.4 (C-4),
73.4 (C-3), 72.6 [OCH2CH(CH2)C(CH3)2], 71.7 (C-2), 69.1 (C-6 minor),
69.0 (C-6 major), 66.7 (C-5), 22.7 [OCH2CH(CH2)CHPh minor] 22.3
[OCH2CH(CH2)CHPh major], 21.7 [OCH2CH(CH2)CHPh minor],
21.6 [OCH2CH(CH2)CHPh major], 14.3 [OCH2CH(CH2)CHPh major],
14.1 [OCH2CH(CH2)CHPh minor]. HRMS (FAB): [M+Na]+, found
421.1607. C23H26O6Na requires 421.1627.
4.4.6. 2-Methyl-2-propenyl 3-O-benzyl-4,6-O-(S)-benzylidene-
b-D
-galactopyranoside 21
The solid was purified by column chromatography using hex-
ane–ethyl acetate (2:1) as eluent. Yield (calculated from the
amount of starting material transformed) 0.3 g (67%); mp 156–
157 °C; [a]D = +6.2 (c 0.5, CH2Cl2); MS (FAB): m/z 435 (50%)
[M+Na]+. 1H NMR (500 MHz, CDCl3): d 7.5–7.2 (m, 10H, 2Ph),
5.46 (s, 1H, PhCH), 5.02, 4.93 [2m, 2H, OCH2C(CH3)@CH2], 4.76 (s,
2H, PhCH2O), 4.34 (d, 1H, J1,2 7.8 Hz, H-1), 4.32–4.28 (m, 2H, H-
6e, OCHAHBC(CH3)@CH2], 4.13 (dd, 1H, J3,4 3.6 Hz, J4,5 0.9 Hz, H-4),
4.09–4.01 [m, 3H, OCHAHBC(CH3)@CH2, H-2, H-6a], 3.50 (dd, 1H,
J2,3 9.7 Hz, J3,4 3.6 Hz, H-3), 3.35 (m, 1H, H-5), 2.41 (d, 1H, J2,OH
2.0 Hz, OH), 1.78 [s, 3H, OCH2C(CH3)@CH2]. 13C NMR (125 MHz,
CDCl3): d 141.3 [OCH2C(CH3)@CH2], 138.2–126.4 (2Ph), 113.1
[OCH2C(CH3)@CH2], 101.5 (C-1), 101.2 (PhCH), 79.3 (C-3), 73.3
(C-4), 72.5 [OCH2C(CH3)@CH2], 71.6 (PhCH2O), 70.1 (C-2), 69.3
(C-6), 66.7 (C-5), 19.6 [OCH2C(CH3)@CH2]. HRMS (FAB): [M+Na]+,
found 435.1792. C24H28O6Na requires 435.1784.
4.5.2. (2S)-3-Methyl-2,3-methylidenebutyl 4,6-O-(S)-benzyli-
dene-b-D-galactopyranoside 24
Two stereoisomers were obtained in a 1.5:1 ratio (20% de). The
pure diastereomeric mixture was obtained as a solid by column
chromatography using dichloromethane–methanol (10:1) as elu-
4.4.7. (E)-2-Methyl-3-phenyl-2-propenyl 3-O-benzyl-4,6-O-(S)-
benzylidene-b-D-galactopyranoside 22
ent. Yield 0.3 g (85%); mp 159–160 °C; [
a
]D = ꢀ36.5 (c 1.0, CH2Cl2);
MS (CI): m/z 351 (5%) [M+H]+. 1H NMR (500 MHz, CDCl3): d 7.55–
7.35 (m, 5H, Ph), 5.56 (s, 0.40H, PhCH minor), 5.55 (s, 0.60H, PhCH
major), 4.36 (d, 0.60H, J1,2 7.6 Hz, H-1 major), 4.33 (m, 1H, H-6e),
4.29 (d, 0.40H, J1,2 7.6 Hz, H-1 minor), 4.21 (m, 1H, H-4), 4.09 (m,
1H, H-6a), 4.04 [dd, 0.40H Jgem 10.7 Hz, J 6.6 Hz, OCHAHBCH(CH2)-
C(CH3)2 minor], 3.89 [dd, 0.60H Jgem 10.8 Hz, J 7.5 Hz, OCHAHB-
CH(CH2)C(CH3)2 major], 3.77 (m, 1H, H-2), 3.71 (m, 1H, H-3), 3.63
[dd, 1H, Jgem 10.8 Hz, J 7.3 Hz, OCHAHBCH(CH2)C(CH3)2 major],
3.50–3.45 [m, 1.40H, H-5, OCHAHBCH(CH2)C(CH3)2 minor], 2.49
(m, 2H, 2OH), 1.11, 1.10, 1.09, 1.08 [4s, 6H, OCH2CH(CH2)C(CH3)2],
0.95 [m, 1H, OCH2CH(CH2)C(CH3)2], 0.54, 0.16 [2 m, 2H,
OCH2CH(CH2)C(CH3)2]. 13C NMR (125 MHz, CDCl3): d 137.6–126.4
(2Ph), 102.2 (C-1 major), 102.1 (C-1 minor), 101.4 (PhCH), 75.4 (C-
4), 72.8 (C-3 major), 72.7 (C-3 minor) 71.8 (C-2 major), 71.7 (C-2
minor), 70.7 [OCH2CH(CH2)C(CH3)2], 69.2 (C-6), 66.7 (C-5 major),
66.6 (C-5 minor) 27.2, 20.0 [OCH2CH(CH2)C(CH3)2 minor], 27.1,
20.0 [OCH2CH(CH2)C(CH3)2 major], 23.5 [OCH2CH(CH2)C(CH3)2
minor], 23.3 [OCH2CH(CH2)C(CH3)2 major], 18.8 [OCH2CH(CH2)-
C(CH3)2], 16.1 [OCH2CH(CH2)C(CH3)2 minor], 15.7 [OCH2CH(CH2)-
C(CH3)2 major]. HRMS (CI): [M+H]+, found 351.1801. C19H27O6 re-
quires 351.1808. Anal. Calcd for C19H26O6: C, 65.13; H, 7.48. Found:
C, 65.35; H, 7.42.
The solid was purified by column chromatography using hexane–
ethyl acetate (3:1) as eluent. Yield 0.3 g (60%); mp 126–127 °C;
[a
]
D = ꢀ27.4 (c 1.0, CH2Cl2); MS (FAB): m/z 511 (65%) [M+Na]+. 1H
NMR (500 MHz, CDCl3): d 7.6–7.2 (m, 15H, 3Ph), 6.55 [s, 1H,
OCH2C(CH3)@CHPh], 5.47 (s, 1H, PhCH), 4.78, 4.75 (2d, 2H, Jgem
12.4 Hz, PhCH2O), 4.45 [d, 1H, Jgem 12.2 Hz, OCHAHBC(CH3)@CHPh],
4.40 (d, 1H, J1,2 7.8 Hz, H-1), 4.34 (dd, 1H, J5,6e 1.4 Hz, J6e,6a 12.3 Hz,
H-6e), 4.22 [d, 1H, Jgem 12.2 Hz, OCHAHBC(CH3)@CHPh], 4.14 (d, 1H,
J3,4 3.4 Hz, H-4), 4.09 (dd, 1H, J1,2 7.9 Hz, J2,3 9.6 Hz, H-2), 4.04 (dd,
1H, J5,6a 1.8 Hz, J6e,6a 12.3 Hz, H-6a), 3.52 (dd, 1H, J2,3 9.7 Hz, J3,4
3.6 Hz, H-3), 3.37 (m, 1H, H-5), 2.45 (s, 1H, OH), 1.94 [d, 3H, 4J
1.1 Hz, OCH2C(CH3)@CHPh]. 13C NMR (125 MHz, CDCl3): d 138.1–
126.6 (3Ph), 134.2 [OCH2C(CH3)@CHPh], 127.9 [OCH2C(CH3)@
CHPh], 101.4 (C-1), 101.1 (PhCH), 79.2 (C-3), 74.9 [OCH2C(CH3)@
CHPh], 73.2 (C-4), 71.6 (PhCH2O), 70.1 (C-2), 69.3 (C-6), 66.7 (C-5),
15.6 [OCH2C(CH3)@CHPh]. HRMS (FAB): [M+Na]+, found 511.2081.
C30H32O6Na requires 511.2097. Anal. Calcd for C30H32O6: C, 73.75;
H, 6.60. Found: C, 73.50; H, 6.62.
4.5. General procedure for cyclopropanation of unsaturated
glycosides
To a solution of the corresponding unsaturated glycosides 3, 6,
17–20, 22 (1.0 mmol) in dry toluene (10–30 mL) at ꢀ15 °C were
added 1.0 M diethylzinc in hexane (5.0 mL, 5.0 mmol) and diiodo-
methane (0.8 mL, 10.0 mmol). The reaction mixture was stirred for
1 h at ꢀ15 °C, and then kept at room temperature until TLC showed
that all the starting material had reacted (ꢁ12 h). The reaction
mixture was diluted with dichloromethane and the reaction was
quenched with saturated ammonium chloride solution. The organ-
ic layer was dried (MgSO4), filtered and evaporated to dryness. The
compounds obtained were purified by flash chromatography on
4.5.3. (2S,3S)-(2-Phenylcyclopropyl)methyl 3-O-benzyl-4,6-O-
(S)-benzylidene-b-D-galactopyranoside 25
Only one stereoisomer was obtained (100% de). The syrup was
purified by column chromatography using hexane–ethyl acetate
(2:1) as eluent. Yield 0.5 g (95%); [
a
]
D = ꢀ22.5 (c 0.8, CH2Cl2); MS
(EI): m/z 488 (3%) [M]+Å. 1H NMR (500 MHz, CDCl3): d 7.6–7.0 (m,
15H, 2Ph), 5.44 (s, 1H, PhCH), 4.78, 4.75 (2d, 2H, PhCH2O), 4.39
(d, 1H, J1,2 7.8 Hz, H-1), 4.15 (dd, 1H, J5,6e 1.3 Hz, J6e,6a 12.3 Hz, H-
6e), 4.12 (d, 1H, J3,4 3.4 Hz, H-4), 4.02 (dt, 1H, J1,2 = J2,3 7.8 Hz,
J2,OH 1.8 Hz, H-2), 3.96 (dd, 1H, J5,6a 1.8 Hz, J6e,6a 12.3 Hz, H-6a),

J. M. Vega-Pérez et al. / Tetrahedron: Asymmetry 21 (2010) 81–95
91
3.87 [dd, 1H, Jgem 10.7 Hz, J 7.0 Hz, OCHAHBCH(CH2)CHPh], 3.64 [dd,
1H, Jgem 10.8 Hz, J 6.7 Hz, OCHAHBCH(CH2)CHPh], 3.50 (dd, 1H, J2,3
9.7 Hz, J3,4 3.6 Hz, H-3), 3.30 (m, 1H, H-5), 2.43 (d, 1H, J2,OH
1.8 Hz, OH), 1.85 [m, 1H, OCH2CH(CH2)CHPh], 1.51 [m, 1H,
OCH2CH(CH2)Ph], 1.00 [m, 1H, OCH2CH(CHAHB)CHPh], 0.94 [m,
1H, OCH2CH(CHAHB)CHPh]. 13C NMR (125 MHz, CDCl3): d 142.5–
125.6 (3Ph), 102.5 (C-1), 101.1 (PhCH), 79.1 (C-3), 73.2 (C-4),
73.1 [OCH2CH(CH2)CHPh], 71.5 (PhCH2O), 70.1 (C-2), 69.2 (C-6),
66.7 (C-5), 22.3 [OCH2CH(CH2)CHPh], 21.5 [OCH2CH(CH2)CHPh],
14.3 [OCH2CH(CH2)CHPh]. HRMS (EI): [M]+Å, found 488.2184.
C30H32O6 requires 488.2199.
1H, Jgem 10.6 Hz, J 7.5 Hz, OCHAHBCH(CH2)CH(CH2)5CH3], 3.32 (m,
1H, H-5), 2.46 (s, 1H, OH), 1.4–1.2, [m, 10H, OCH2CH(CH2)CH-
(CH2)5CH3], 0.90–0.83 [m, 4H, OCH2CH(CH2)CH(CH2)5CH3], 0.61
[m, 1H, OCH2CH(CH2)CH(CH2)5CH3], 0.41–033 [m, 2H, OCH2-
CH(CH2)CH(CH2)5CH3]. 13C NMR (125 MHz, CDCl3): d 138.0–125.3
(2Ph), 102.1 (C-1), 101.1 (PhCH), 78.9 (C-3), 73.6 [OCH2CH(CH2)-
CH(CH2)5CH3], 73.2 (C-4), 71.5 (PhCH2O), 70.1 (C-2), 69.2 (C-6),
66.6 (C-5), 33.6–29.4 [OCH2CH(CH2)CH(CH2)5CH3], 22.7 [OCH2CH-
(CH2)CH(CH2)5CH3], 17.8 [OCH2CH(CH2)CH(CH2)5CH3], 14.1 [OCH2-
CH(CH2)CH(CH2)5CH3], 10.1 [OCH2CH(CH2)CH(CH2)5CH3]. HRMS
(FAB): [M+Na]+, found 533.2874. C31H42O6Na requires 533.2879.
4.5.4. (2S)-3-Methyl-2,3-methylidenebutyl 3-O-benzyl-4,6-O-
(S)-benzylidene-b-D-galactopyranoside 26
Only one stereoisomer was obtained (100% de). The syrup was
purified by column chromatography using hexane–ethyl acetate
4.5.7. (1S,2R)-(1-Methyl-2-phenylcyclopropyl)methyl 3-O-
benzyl-4,6-O-(S)-benzylidene-b-D-galactopyranoside 29
Two stereoisomers were obtained in an 8.1:1 ratio (78% de). The
pure diastereomeric mixture was obtained as a syrup by column
chromatography using hexane–ethyl acetate (3:1) as eluent. Yield
(1.5:1) as eluent. Yield 0.4 g (91%); [
a
]
D = ꢀ56.6 (c 0.3, CH2Cl2); MS
(EI): m/z 440 (5%) [M]+Å. 1H NMR (500 MHz, CDCl3): d 7.55–7.25 (m,
10H, 2Ph), 5.46 (s, 1H, PhCH), 4.77 (s, 2H, PhCH2O), 4.38 (d, 1H, J1,2
7.8 Hz, H-1), 4.30 (dd, 1H, J5,6e 1.4 Hz, J6e,6a 12.3 Hz, H-6e), 4.12 (d,
1H, J3,4 3.3 Hz, H-4), 4.04–4.00 (m, 2H, H-2, H-6a), 3.87 [dd, Jgem
10.8 Hz, J 7.5 Hz, OCHAHBCH(CH2)C(CH3)2], 3.62 [dd, 1H, Jgem
10.8 Hz, J 7.2 Hz, OCHAHBCH(CH2)C(CH3)2], 3.51 (dd, 1H, J2,3 9.7 Hz,
J3,4 3.6 Hz, H-3), 3.34 (m, 1H, H-5), 2.45 (d, 1H, J2,OH 1.7 Hz, OH),
1.09, 1.07 [2s, 6H, OCH2CH(CH2)C(CH3)2], 0.94 [m, 1H, OCH2CH-
0.3 g (67%); [a]D = +34.0 (c 0.8, CH2Cl2); MS (FAB): m/z 525 (15%)
[M+H]+. 1H NMR (500 MHz, CDCl3): d 7.60–7.15 (m, 15H, 3Ph),
5.48 (s, 1H, PhCH), 4.78 (s, 2H, PhCH2O), 4.40 (d, 1H, J1,2 7.8 Hz, H-
1), 4.31 (dd, 1H, J5,6e 1.5 Hz, J6e,6a 12.3 Hz, H-6e), 4.15 (d, 1H, J3,4
2.7 Hz, H-4), 4.08–4.02 (m, 2H, H-2, H-6a), 3.87 [d, 0.11H Jgem
10.3 Hz, OCHAHBC(CH3)(CH2)CHPh minor], 3.82 [d, 0.89H Jgem
10.2 Hz, OCHAHBC(CH3)(CH2)CHPh major], 3.60–3.50 [m, 2H,
OCHAHBC(CH3)(CH2)CHPh, H-3), 3.64 (m, 1H, H-5), 2.43 (s, 1H,
OH), 2.11 [m, 1H, OCH2C(CH3)(CH2)CHPh], 0.97 [m, 1H, OCH2-
C(CH3)(CHAHB)CHPh], 0.90–0.85 [m, 4H, OCH2CH(CH3)(CHAHB)-
CHPh]. 13C NMR (125 MHz, CDCl3): d 138.9–125.8 (3Ph), 102.7
(C-1), 101.1 (PhCH), 79.1 (C-3), 77.7 [OCH2C(CH3)(CH2)CHPh], 73.4
(C-4), 71.6 (PhCH2O), 70.3 (C-2), 69.3 (C-6), 66.8 (C-5), 26.6 [OCH2-
C(CH3)(CH2)CHPh], 22.6 [OCH2C(CH3)(CH2)CHPh], 16.3 [OCH2C-
(CH3)(CH2)CHPh], 15.8 [OCH2C(CH3)(CH2)CHPh]. HRMS (FAB): [M+
Na]+, found 525.2250. C31H34O6Na requires 525.2253.
(CH2)C(CH3)2], 0.53 [dd, 1H, Jgem 4.5 Hz,
J 8.5 Hz, OCH2CH-
(CHAHB)C(CH3)2], 0.15 [dd, 1H, Jgem 4.6 Hz, J 4.9 Hz, OCH2CH-
(CHAHB)C(CH3)2]. 13C NMR (125 MHz, CDCl3): d 138.2–126.4 (2Ph),
102.2 (C-1), 101.2 (PhCH), 79.1 (C-3), 73.3 (C-4), 71.5 (PhCH2O),
70.4 [OCH2CH(CH2)C(CH3)2], 70.1 (C-2), 69.3 (C-6), 66.7 (C-5), 27.2,
20.0 [OCH2CH(CH2)C(CH3)2], 23.3 [OCH2CH(CH2)C(CH3)2], 18.8
[OCH2CH(CH2)C(CH3)2], 15.7 [OCH2CH(CH2)C(CH3)2]. HRMS (EI):
[M]+Å, found 440.2202. C26H32O6 requires 440.2199.
4.5.5. (2S,3S)-2,3-Methylidenebutyl 3-O-benzyl-4,6-O-(S)-benzyl-
idene-b-D-galactopyranoside 27
4.6. Separation of chiral auxiliary9
Two stereoisomers were obtained in an 11.5:1 ratio (84% de). The
pure diastereomeric mixture was obtained as a solid by column
chromatography using hexane–ethyl acetate (2:1) as eluent. Yield
To a solution of compound 25 or 28 (1.0 mmol) in dichloro-
methane (2 mL) cooled to ꢀ20 °C, pyridine (17 mmol) and trifluo-
romethanesulfonic anhydride (4.8 mmol) were added over 20 min.
The reaction mixture was then warmed slowly to 0 °C over 1 h and
stirred at that temperature until TLC analysis showed complete
consumption of the starting material. The reaction mixture was di-
luted with dichloromethane and washed with saturated aqueous
sodium bicarbonate and brine, and the organic layer was dried
(MgSO4) and evaporated to dryness. The residue was dissolved in
dimethylformamide (100 mL) and pyridine (2 mL) and water
(2 mL) were added. The reaction mixture was heated at 150 °C
for 30 min and then cooled to room temperature. The solution
was diluted with diethyl ether–ethyl acetate (1:1) (100 mL) and
washed successively with 10% aqueous hydrochloric acid and
water. The organic layer was dried (MgSO4) and evaporated to dry-
ness. The compound obtained was purified by column chromatog-
raphy using hexane–ethyl acetate mixtures as eluent.
0.4 g (91%); [
a]
D = ꢀ12.8 (c 0.5, CH2Cl2); MS (FAB): m/z 449 (50%)
[M+Na]+. 1H NMR (500 MHz, CDCl3): d 7.55–7.25 (m, 10H, 2Ph),
5.46 (s, 1H, PhCH), 4.77 (s, 2H, PhCH2O), 4.39 (d, 0.08H, J1,2 7.8 Hz,
H-1 minor), 4.35 (d, 0.92H, J1,2 7.8 Hz, H-1 major), 4.29 (dd, 1H,
J5,6e 1.6 Hz, J6e,6a 12.3 Hz, H-6e), 4.12 (dd, 1H, J3,4 3.6 Hz, J4,5 0.9 Hz,
H-4), 4.05–4.00 (m, 2H, H-2, H-6a), 3.75 [dd, Jgem 10.6 Hz, J 7.0 Hz,
OCHAHBCH(CH2)CHCH3], 3.50 (dd, 1H, J2,3 9.7 Hz, J3,4 3.6 Hz, H-3),
3.42 [dd, 1H, Jgem 10.6 Hz, J 7.1 Hz, OCHAHBCH(CH2)CHCH3], 3.33
(m, 1H, H-5), 2.45 (s, 1H, OH), 1.05 [d, 3H, J 6.0 Hz, OCH2-
CH(CH2)CHCH3], 0.85, 0.66 [2m, 2H, OCH2CH(CH2)CHCH3], 0.39,
031 [2m, 2H, OCH2CH(CH2)CHCH3]. 13C NMR (125 MHz, CDCl3): d
138.2–126.4 (2Ph), 102.4 (C-1), 101.1 (PhCH), 79.2 (C-3), 73.6 (C-
4), 73.3 [OCH2CH(CH2)CHCH3], 71.6 (PhCH2O), 70.1 (C-2) , 69.3 (C-
6), 66.7 (C-5), 19.0, 18.4, 11.7, 11.2 [OCH2CH(CH2)CHCH3]. HRMS
(FAB): [M+Na]+, found 449.1914. C25H30O6Na requires 449.1940.
4.6.1. (1S,2S)-trans-1-Hydroxymethyl-2-phenylcyclopropane
4.5.6. (2S,3S)-2,3-Methylidenedecyl 3-O-benzyl-4,6-O-(S)-benzy-
lidene-b-D-galactopyranoside 28
(+)-3029
A syrup was obtained. Yield 48 mg (60%); [
a
]
D = +69.3 (c 0.8,
Only one stereoisomer was obtained (100% de). The syrup was
purified by column chromatography using hexane–ethyl acetate
CH2Cl2), {lit.29b for (R,R)-enantiomer [
a]
D = ꢀ56.2 (c 0.60, CHCl3)
for 75% ee}; MS (CI): m/z 149 (20%) [M+H]+. 1H NMR (500 MHz,
CDCl3): d 7.6–7.1 (m, 5H, Ph), 3.63 [dd, 2H, J 6.8 Hz, Jgem 11.3 Hz,
HOCH2CH(CH2)CHPh], 1.84 [m, 1H, HOCH2CH(CH2)CHPh], 1.47
[m, 1H, HOCH2CH(CH2)CHPh], 0.98 [m, 2H, HOCH2CH(CH2)CHPh].
13C NMR (125 MHz, CDCl3): d 136.7–128.1 (Ph), 66.5 [HOCH2-
CH(CH2)CHPh], 25.2 [HOCH2CH(CH2)CHPh], 21.3 [HOCH2CH(CH2)-
CHPh], 13.7 [HOCH2CH(CH2)CHPh].
(3:1) as eluent. Yield 0.5 g (91%); [
a]
D = ꢀ27.4 (c 0.5, CH2Cl2); MS
(FAB): m/z 533 (50%) [M+Na]+. 1H NMR (500 MHz, CDCl3): d 7.55–
7.25 (m, 10H, 2Ph), 5.46 (s, 1H, PhCH), 4.77 (s, 2H, PhCH2O), 4.36
(d, 1H, J1,2 7.8 Hz, H-1), 4.29 (dd, 1H, J5,6e 1.5 Hz, J6e,6a 12.3 Hz,
H-6e), 4.12 (dd, 1H, J3,4 3.3 Hz, J4,5 0.8 Hz, H-4), 4.03–4.00 (m, 2H,
H-2, H-6a), 3.82 [dd, Jgem 10.6 Hz, J 6.7 Hz, OCHAHBCH(CH2)-
CH(CH2)5CH3], 3.50 (dd, 1H, J2,3 9.7 Hz, J3,4 3.6 Hz, H-3), 3.36 [dd,

92
J. M. Vega-Pérez et al. / Tetrahedron: Asymmetry 21 (2010) 81–95
4.6.2. (1S,2S)-trans-1-Heptyl-2-hydroxymethylcyclopropane (+)-31
A syrup was obtained. Yield 100 mg (75%); [ D = +16.8 (c 0.5,
CH2Cl2), {lit.14 ent-form [
D = –17.6 (c 0.50, CH2Cl2)}; MS (CI): m/z
minor], 55.9 [OCH2CH(O)CHPh major]. HRMS (FAB): [M+Na]+, found
423.1441. C22H24O7Na requires 423.1420.
a]
a]
171 (5%) [M+H]+. 1H NMR (500 MHz, CDCl3): d 3.44 [m, 2H,
HOCH2CH(CH2)CH(CH2)6CH3], 1.60–1.15 [m, 13H, HOCH2CH(CH2)-
CH(CH2)6CH3], 0.88 [t, 3H, J 6.9 Hz, HOCH2CH(CH2)CH(CH2)6CH3],
0.83 [m, 1H, HOCH2CH(CH2)CH(CH2)6CH3], 0.59 [m, 1H, HOCH2-
CH(CH2)CH(CH2)6CH3], 0.36, 0.30 [2 m, 2H, HOCH2CH(CH2)CH-
(CH2)6CH3]. 13C NMR (125 MHz, CDCl3): d 67.3 [HOCH2CH(CH2)-
CH(CH2)6CH3], 33.6, 31.9, 29.6, 29.4, 29.3, 22.7 [HOCH2CH(CH2)-
CH(CH2)6CH3], 21.2 [HOCH2CH(CH2)CH(CH2)6CH3], 17.4 [HOCH2-
CH(CH2)CH(CH2)6CH3], 14.1 [HOCH2CH(CH2)CH(CH2)6CH3], 9.9
[HOCH2CH(CH2)CH(CH2)6CH3].
4.7.1.3. (2S,3S)-2,3-Epoxybutyl 4,6-O-(S)-benzylidene-b-D-galac-
topyranoside 34. Two stereoisomers were obtained in a 9:1 ratio
(80% de). The pure diastereomeric mixture was obtained as a solid
by column chromatography using hexane–ethyl acetate (1:6) as
eluent. Yield 0.2 g (56%); mp 149–150 °C; [
a
]D = ꢀ37.2 (c 0.5,
CH2Cl2); MS (FAB): m/z 361 (100%) [M+Na]+. 1H NMR (500 MHz,
CDCl3): d 7.50–7.30 (m, 5H, Ph), 5.55 (s, 1H, PhCH), 4.40 (d,
0.10H, J1,2 7.7 Hz, H-1 minor), 4.35–4.30 (m, 1.90H, H-1 major, H-
6e), 4.21 (d, 1H, J3,4 3.7 Hz, H-4), 4.09 (dd, 1H, J5,6a 1.8 Hz, J6e,6a
12.5 Hz, H-6a), 4.00 [dd, 0.90H Jgem 12.0 Hz, J 4.3 Hz, OCHAHB-
CH(O)CHCH3 major], 3.84 [dd, 0.90H Jgem 12.0 Hz, J 3.2 Hz, OCHAHB-
CH(O)CHCH3 major], 3.77 (dd, 1H, J1,2 7.7 Hz, J2,3 9.4 Hz, H-2), 3.68
(dt, 1H, J2,3 9.4 Hz, J3,4 3.7 Hz, J3,OH 8.7 Hz, H-3), 3.58 [dd, 0.10H Jgem
11.9 Hz, J 6.0 Hz, OCHAHBCH(O)CHCH3 minor], 3.49 (m, 1H, H-5),
3.07 [m, 1H, OCH2CH(O)CHCH3], 2.96 [m, 1H, OCH2CH(O)CHCH3],
2.92 (s, 1H, 2-OH), 2.56 (d, 1H, J3,OH 8.6 Hz, 3-OH), 1.34 [d, 3H, J
5.3 Hz, OCH2CH(O)CHCH3]. 13C NMR (125 MHz, CDCl3): d 137.4–
126.4 (Ph), 103.3 (C-1), 101.4 (PhCH), 75.2 (C-4), 72.7 (C-3), 71.7
(C-2), 69.1 (C-6), 68.6 [OCH2CH(O)CHCH3], 66.8 (C-5), 57.9 [OCH2-
CH(O)CHCH3 minor], 57.7 [OCH2CH(O)CHCH3 major], 52.2 [OCH2-
CH(O)CHCH3], 17.2 [OCH2CH(O)CHCH3 major], 15.3 [OCH2CH(O)-
CHCH3 minor]. HRMS (FAB): [M+Na]+, found 361.1244. C17H22O7Na
requires 361.1263. Anal. Calcd for C17H22O7: C, 60.35; H, 6.55.
Found: C, 59.95; H, 6.35.
4.7. General procedure for the epoxidation of unsaturated
glycosides
To a solution of the corresponding unsaturated glycosides 2–10,
14, 16–19, 21 and 22 (1.0 mmol) in chloroform (75 mL) was added
a solution of m-chloroperoxybenzoic acid (Aldrich 57–86%) (1.5 g)
in chloroform (25 mL), previously dried over MgSO4. The reaction
mixture was kept at ꢀ15 °C until TLC showed that all starting com-
pound had been consumed (7 days); then, the solution was washed
successively with 5% aqueous sodium hydroxide (7 ꢂ 30 mL) and
water, dried (MgSO4), filtered and the filtrate was evaporated to
dryness. The diastereomeric excess (de) was determined by 1H
NMR.
4.7.1. Epoxidation of 4,6-O-benzylidene derivatives
4.7.1.4. (2S,3S)-2,3-Epoxydecyl 4,6-O-(S)-benzylidene-b-D-galac-
4.7.1.1. (2R)-2,3-Epoxypropyl 4,6-O-(S)-benzylidene-b-
D
-galac-
topyranoside 35. Two stereoisomers were obtained in an 8.9:1
ratio (80% de). The pure diastereomeric mixture was obtained as
a syrup by column chromatography using hexane–ethyl acetate
topyranoside 32. Only one stereoisomer was obtained (100%
de). The pure compound was obtained as a syrup by column chro-
matography using hexane–ethyl acetate (1:5) as eluent. Yield 0.2 g
(1:6) as eluent. Yield 0.3 g (74%); [
a
]D = ꢀ17.3 (c 0.5, CH2Cl2); MS
(63%); [
a
]
D = ꢀ31.2 (c 0.5, CH2Cl2); MS (CI): m/z 325 (5%) [M+H]+.
(FAB): m/z 445 (100%) [M+Na]+. 1H NMR (500 MHz, CDCl3): d
7.55–7.30 (m, 5H, Ph), 5.55 (s, 1H, PhCH), 4.41 (d, 0.10H, J1,2
7.8 Hz, H-1 minor), 4.33–4.31 (m, 1.90H, H-1 major, H-6e), 4.20
(d, 1H, J3,4 3.7 Hz, H-4), 4.15 [dd, 0.10H Jgem 12.0 Hz, J 2.9 Hz,
OCHAHBCH(O)CH(CH2)6CH3 minor], 4.08 (dd, 1H, J5,6a 1.8 Hz, J6e,6a
12.5 Hz, H-6a), 3.99 [dd, 0.90H Jgem 12.0 Hz, J 4.1 Hz, OCHAHB-
CH(O)CH(CH2)6CH3 major], 3.85 [dd, 0.90H Jgem 12.0 Hz, J 2.8 Hz,
OCHAHBCH(O)CH(CH2)6CH3 major], 3.76 (dd, 1H, J1,2 7.8 Hz, J2,3
9.4 Hz, H-2), 3.68 (dt, 1H, J2,3 9.5 Hz, J3,4 3.7 Hz, J3,OH 8.6 Hz, H-3),
3.54 [dd, 0.10H Jgem 12.0 Hz, J 6.3 Hz, OCHAHBCH(O)CH(CH2)6CH3
minor], 3.48 (m, 1H, H-5), 3.08 (s, 0.90H, 2-OH major), 3.04 (s,
0.10H, 2-OH minor), 3.02–2.97 [m, 2H, OCH2CH(O)CH(CH2)6CH3],
2.64 (d, 1H, J3,OH 8.6 Hz, 3-OH), 1.6–1.2 [m, 12H, OCH2CH(O)-
CH(CH2)6CH3], 0.88 [t, 3H, J 7.0 Hz, OCH2CH(O)CH(CH2)6CH3]. 13C
NMR (125 MHz, CDCl3): d 137.5–126.4 (Ph), 103.3 (C-1 major),
102.3 (C-1 minor), 101.4 (PhCH), 75.2 (C-4), 72.7 (C-3 major),
72.6 (C-3 minor), 71.7 (C-2 major), 71.2 (C-2 minor), 69.1 (C-6),
68.8 [OCH2CH(O)CH(CH2)6CH3], 66.8 (C-5), 56.9, 56.3 [OCH2-
CH(O)CH(CH2)6CH3 minor], 56.7, 56.0 [OCH2CH(O)CH(CH2)6CH3
major], 31.7, 31.6, 29.3, 29.1, 25.9, 22.6 [OCH2CH(O)CH(CH2)6CH3],
14.1 [OCH2CH(O)CH(CH2)6CH3]. HRMS (FAB): [M+Na]+, found
445.2215. C23H34O7Na requires 445.2202.
1H NMR (500 MHz, CDCl3): d 7.6–7.3 (m, 5H, Ph), 5.55 (s, 1H,
PhCH), 4.4–4.3 (m, 2H, H-1, H-6e), 4.21 (d, 1H, J3,4 3.5 Hz, H-4),
4.02 (d, 1H, J6e,6a 12.4 Hz, H-6a), 3.98 [dd, 1H, Jgem 12.0 Hz, J
4.4 Hz, OCHAHBCH(O)CH2], 3.90 [dd, 1H, Jgem 12.0 Hz, J 3.0 Hz,
OCHAHBCH(O)CH2], 3.78 (m, 1H, H-2), 3.70 (m, 1H, H-3), 3.49 (m,
1H, H-5), 3.25 [m, 1H, OCH2CH(O)CH2], 2.83 [m, 1H, OCH2CH(O)-
CHAHB], 2.78 [m, 1H, OCH2CH(O)CHAHB]. 13C NMR (125 MHz,
CDCl3): d 137.4–126.4 (Ph), 103.2 (C-1), 101.4 (PhCH), 75.2 (C-4),
72.7 (C-3), 71.7 (C-2), 69.1 (C-6), 69.0 [OCH2CH(O)CH2], 66.8 (C-
5), 50.7 [OCH2CH(O)CH2], 44.6 [OCH2CH(O)CH2]. HRMS (CI):
[M+H]+, found 325.1287. C16H21O7 requires 325.1287.
4.7.1.2. (2S,3S)-2,3-Epoxy-3-phenylpropyl
4,6-O-(S)-benzyli-
dene-b- -galactopyranoside 33. Two stereoisomers were ob-
D
tained in a 12.5:1 ratio (85% de). The pure diastereomeric mixture
was obtained as a syrup by column chromatography using hex-
ane–ethyl acetate (1:4) as eluent. Yield 0.3 g (72%); [
a
]D = ꢀ26.5 (c
0.4, CH2Cl2); MS (FAB): m/z 423 (100%) [M+Na]+. 1H NMR
(500 MHz, CDCl3): d 7.6–7.2 (m, 10H, 2Ph), 5.55 (s, 0.93H, PhCH ma-
jor), 5.54 (s, 0.07H, PhCH minor), 4.46 (d, 0.07H, J1,2 7.8 Hz, H-1 min-
or), 4.39 (d, 0.93H, J1,2 7.7 Hz, H-1 major), 4.33 (dd, 0.93H, J5,6e 1.4 Hz,
J6e,6a 12.5 Hz, H-6e major), 4.26 (dd, 0.07H, J5,6e 1.4 Hz, J6e,6a 12.5 Hz,
H-6e minor), 4.21 (d, 1H, J3,4 3.0 Hz, H-4), 4.15–4.05 [m, 2H, OCHAHB-
CH(O)CHPh, H-6a], 4.01 [dd, 1H, Jgem 12.1 Hz, J 2.8 Hz, OCHAHB-
CH(O)CHPh], 3.96 [d, 1H, J 2.0 Hz, OCH2CH(O)CHPh], 3.81 (m, 1H,
H-2), 3.70 (m, 1H, H-3), 3.49 (m, 1H, H-5), 3.33 [m, 0.07H, OCH2-
CH(O)CHPh minor], 3.28 [m, 0.93H, OCH2CH(O)CHPh major], 3.04
(s, 1H, 2-OH), 2.68 (s, 1H, 3-OH). 13C NMR (125 MHz, CDCl3): d
137.5–125.8 (2Ph), 103.3 (C-1 major), 102.6 (C-1 minor), 101.4
(PhCH), 75.2 (C-4), 72.7 (C-3), 71.7 (C-2 major), 71.2 (C-2 minor),
69.1 (C-6), 68.7 [OCH2CH(O)CHPh minor], 68.2 [OCH2CH(O)CHPh
major], 66.8 (C-5), 60.5 [OCH2CH(O)CHPh], 56.2 [OCH2CH(O)CHPh
4.7.1.5. (2S)-2,3-Epoxy-3-methylbutyl 4,6-O-(S)-benzylidene-b-
D-galactopyranoside 36. Two stereoisomers were obtained in a
1.6:1 ratio (23% de). The pure diastereomeric mixture was obtained
as a solid by column chromatography using hexane–ethyl acetate
(1:4) as eluent. Yield 0.3 g (92%); mp 148–149 °C, [
a
]D = ꢀ17.3 (c
1.0, CH2Cl2); MS (FAB): m/z 375 (100%) [M+Na]+. 1H NMR
(500 MHz, CDCl3): d 7.55–7.30 (m, 5H, Ph), 5.51 (s, 1H, PhCH),
4.33–4.25 (m, 2H, H-1, H-6e), 4.15–4.00 (m, 2H, H-4, H-6a), 3.95
[dd, 0.38H Jgem 11.5 Hz, J 6.0 Hz, OCHAHBCH(O)C(CH3)2 minor],
3.81–3.74 [m, 1.62H, H-2, OCHAHBCH(O)C(CH3)2 major], 3.69–

J. M. Vega-Pérez et al. / Tetrahedron: Asymmetry 21 (2010) 81–95
93
3.59 [m, 2H, H-3, OCHAHBCH(O)C(CH3)2], 3.42 (m, 1H, H-5), 3.06
[m, 1H, OCH2CH(O)C(CH3)2], 2.72, 2.59 (2 m, 2H, 2OH), 1.33, 1.29
[2s, 1.14H, OCH2CH(O)C(CH3)2 minor], 1.30, 1.27 [2s, 1.86H, OCH2-
CH(O)C(CH3)2 major]. 13C NMR (125 MHz, CDCl3): d 137.6–126.4
(Ph), 102.7 (C-1), 101.3 (PhCH), 75.4 (C-4 major), 75.3 (C-4 minor),
72.6 (C-3 minor), 72.5 (C-3 major), 71.5 (C-2 major), 71.2 (C-2 min-
or), 69.1 (C-6), 68.0 [OCH2CH(O)C(CH3)2], 66.7 (C-5), 61.7 [OCH2-
(m, 3H, 2-PhCHAHBO, 3-PhCH2O) 4.49 (d, 0.39H, J1,2 7.8 Hz, H-1
minor), 4.44 (d, 0.61H, J1,2 7.8 Hz, H-1 major), 4.28 (dd, 1H, J5,6e
5.0 Hz, J6e,6a 12.3 Hz, H-6e), 4.14 (d, 0.39H, J3,4 = J4,5 3.2 Hz, H-4
minor), 4.12 (d, 0.61H, J3,4 = J4,5 3.5 Hz, H-4 major), 4.02 (d,
0.61H, Jgem 12.2, H-6a major), 4.01 (d, 0.39H, Jgem 12.4, H-6a minor),
3.98 (d, 0.39H, J2,3 = J3,4 4.8 Hz, H-3 minor), 3.95 (d, 0.61H, J2,3 = J3,4
4.7 Hz, H-3 major), 3.9–3.8 [m, 2H, OCHAHBCH(O)CH2, H-2] , 3.6–
3.5 (m, 1H, OCHAHBCH(O)CH2), 3.33 (br s, 1H, H-5), 3.22 [m, 1H,
OCH2CH(O)CH2], 2.83 [m, 1H, OCH2CH(O)CHAHB], 2.72 [dd, 0.61H,
J 2.7 Hz, J 4.9 Hz, OCH2CH(O)CHAHB major], 2.60 [dd, 0.39H, J
2.7 Hz, J 4.9 Hz, OCH2CH(O)CHAHB minor]. 13C NMR (125 MHz,
CDCl3): d 138.7–126.4 (3Ph), 103.7 (C-1 major), 103.4 (C-1 minor),
101.3 (PhCH), 79.1 (C-3 major), 79.0 (C-3 minor), 78.4 (C-2 minor),
78.3 (C-2 major), 75.3 (2-PhCH2O), 73.9 (C-4 minor), 73.8 (C-4
mayor), 72.1 (3-PhCH2O minor), 72.0 (3-PhCH2O major), 70.5
[OCH2CH(O)CH2], 69.4 (C-6 minor), 69.2 (C-6 major), 66.5 (C-5 ma-
jor), 66.4 (C-5 minor), 50.8 [OCH2CH(O)CH2 minor], 50.6 [OCH2-
CH(O)CH2 major], 44.5 [OCH2CH(O)CH2]. HRMS (EI): [M]+Å, found
504.2109. C30H32O7 requires 504.2148.
CH(O)C(CH3)2],
58.3
[OCH2CH(O)C(CH3)2
minor],
57.9
[OCH2CH(O)C(CH3)2 major], 24.6, 18.8 [OCH2CH(O)C(CH3)2 minor],
24.5, 18.9 [OCH2CH(O)C(CH3)2 major]. HRMS (FAB): [M+Na]+,
found 375.1438. C18H24O7Na requires 375.1420. Anal. Calcd for
C18H24O7: C, 61.35; H, 6.86. Found: C, 60.56; H, 6.88.
4.7.1.6. (2R)-2,3-Epoxy-2-methylpropyl 4,6-O-(S)-benzylidene-
b-D-galactopyranoside 37. Two stereoisomers were obtained in
a 15:1 ratio (88% de). The pure diastereomeric mixture was ob-
tained as a syrup by column chromatography using hexane–ethyl
acetate (1:4) as eluent. Yield 0.3 g (79%); [
a]D = ꢀ19.2 (c 0.9,
CH2Cl2); MS (CI): m/z 339 (50%) [M+H]+. 1H NMR (500 MHz, CDCl3):
d 7.6–7.3 (m, 5H, Ph), 5.57 (s, 0.06H, PhCH minor), 5.55 (s, 0.94H,
PhCH major), 4.40 (d, 0.06H, J 7.8 Hz, H-1 minor), 4.35–4.30 (m,
1.94H, H-1 major, H-6e), 4.20 (dd, 1H, J3,4 3.7 Hz, J4,5 0.8 Hz, H-4),
4.08 (dd, 1H, J5,6a 1.8 Hz, J6e,6a 12.5 Hz, H-6a), 4.01 [d, 1H Jgem
11.7 Hz, OCHAHBC(CH3)(O)CH2], 3.78 (m, 0.06H, H-2 minor) 3.76
(dd, 0.94H, J1,2 7.6 Hz, J2,3 9.6 Hz, H-2 major), 3.7–3.6 [m, 2H, H-3,
OCHAHBC(CH3)(O)CH2], 3.47 (m, 1H, H-5), 2.97 [d, 1H, Jgem 4.9 Hz,
OCH2C(CH3)(O)CHAHB], 2.64 [d, 1H, Jgem 4.9 Hz, OCH2C(CH3)(O)-
CHAHB], 1.34 (s, 0.18H, OCH2C(CH3)(O)CH2 minor], 1.38 (s, 2.88H,
OCH2C(CH3)(O)CH2 major]. 13C NMR (125 MHz, CDCl3): d 137.5–
126.4 (Ph), 103.6 (C-1), 101.4 (PhCH), 75.2 (C-4), 72.8 (C-3), 71.8
(C-2), 71.0 [OCH2C(CH3)(O)CH2], 69.1 (C-6), 66.8 (C-5), 56.2
[OCH2C(CH3)(O)CH2], 51.3 [OCH2C(CH3)(O)CH2], 18.6 [OCH2C(-
CH3)(O)CH2]. HRMS (CI): [M+H]+, found 339.1446. C17H23O7 re-
quires 339.1444.
4.7.2.2. (2S,3S)-2,3-Epoxy-3-phenylpropyl 2,3-di-O-benzyl-4,6-
O-(S)-benzylidene-b-D-galactopyranoside 40. Two stereoisomers
were obtained in a 1.2:1 ratio (9% de). The pure diastereomeric mix-
ture was obtained as a syrup by column chromatography using hex-
ane–ethyl acetate (3:1) as eluent. Yield 0.4 g (72%); [
a
]
D = ꢀ30.3 (c
0.4, CH2Cl2); MS (EI): m/z 580 (10%) [M]+Å. 1H NMR (500 MHz, CDCl3):
d 7.6–7.2 (m, 20H, 4Ph), 5.52 (s, 0.55H, PhCH major), 5.50 (s, 0.45H,
PhCH minor), 4.96 (d, 0.55H, Jgem 10.6 Hz, 2-PhCHAHBO major), 4.94
(d, 0.45H, Jgem 10.6 Hz, 2-PhCHAHBO minor), 4.8–4.7 (m, 3H, 2-
PhCHAHBO, 3-PhCH2O), 4.56 (d, 0.45H, J1,2 7.9 Hz, H-1 minor), 4.51
(d, 0.55H, J1,2 7.9 Hz, H-1 major), 4.38 (m, 0.45H, H-6e minor), 4.32
(m, 0.55H, H-6e major), 4.2–4.1 (m, 2H, H-4, H-6a), 4.0–3.9 [m, 3H,
H-2, OCHAHBCH(O)CHPh, OCH2CH(O)CHPh], 3.80 (d, 0.45H, J2,3
=
J3,4 5.0 Hz, H-3 minor), 3.78 (d, 0.55H, J2,3 = J3,4 5.1 Hz, H-3 major),
3.36 (m, 0.45H, H-5 minor), 3.33 (m, 0.55H, H-5 major), 3.30 [m,
0.45H, OCH2CH(O)CHPh minor], 3.27 [m, 0.55H, OCH2CH(O)CHPh
major] .13C NMR (125 MHz, CDCl3): d 138.7–125.7 (4Ph), 103.8 (C-
1 major), 103.6 (C-1 minor), 101.3 (PhCH major), 101.2 (PhCH min-
or), 79.1 (C-3), 78.4 (C-2 major), 78.3 (C-2 minor), 75.4 (2-PhCH2O
minor), 75.3 (2-PhCH2O major), 73.9 (C-4), 72.0 (3-PhCH2O), 69.2
[OCH2CH(O)CHPh], 68.3(C-6) 66.6 (C-5), 61.4 [OCH2CH(O)CHPh
minor], 60.8 [OCH2CH(O)CHPh major], 56.3 [OCH2CH(O)CHPh min-
or], 56.0 [OCH2CH(O)CHPh major]. HRMS (EI): [M]+Å, found
580.2466. C36H36O7 requires 580.2461.
4.7.1.7. (2S,3S)-2,3-Epoxy-2-methyl-3-phenylpropyl 4,6-O-(S)-
benzylidene-b-D-galactopyranoside 38. Two stereoisomers were
obtained in a 7.3:1 ratio (76% de). The pure diastereomeric mixture
was obtained as a syrup by column chromatography using hex-
ane–ethyl acetate (1:4) as eluent. Yield 0.3 g (80%); [
a]
D = ꢀ20.1 (c
0.7, CH2Cl2); MS (EI): m/z 414 (8%) [M]+Å. 1H NMR (500 MHz, CDCl3):
d 7.6–7.2 (m, 10H, 2Ph), 5.56 (s, 1H, PhCH), 4.49 (d, 0.12H, J1,2 7.8 Hz,
H-1 minor), 4.40 (d, 0.88H, J1,2 7.8 Hz, H-1 major), 4.36 (dd, 1H, J5,6e
1.4 Hz, J6e,6a 12.4 Hz, H-6e), 4.29 [s, 1H, OCH2C(CH3)(O)CHPh], 4.22
(d, 1H, J3,4 3.0 Hz, H-4), 4.14 [d, 1H, Jgem 12.0 Hz, OCHAHB
C(CH3)(O)CHPh], 4.10 (dd, 1H, J5,6a 1.8 Hz, J6e,6a 12.4 Hz, H-6a),
3.85–3.80 [m, 2H, OCHAHBC(CH3)(O)CHPh, H-2], 3.75 (m, 0.12H, H-
3 minor), 3.73 (m, 0.88H, H-3 major), 3.51 (m, 1H, H-5), 1.10 [s, 3H,
OCH2C(CH3)(O)CHPh]. 13C NMR (125 MHz, CDCl3): d 137.4–126.4
(2Ph), 103.7 (C-1), 101.4 (PhCH), 75.2 (C-4), 72.6 (C-3), 71.7 (C-2),
71.5 [OCH2C(CH3)(O)CHPh minor], 71.3 [OCH2C(CH3)(O)CHPh
major], 69.1 (C-6), 66.8 (C-5), 62.8 [OCH2C(CH3)(O)CHPh], 60.7
[OCH2C(CH3)(O)CHPh minor], 60.4 [OCH2C(CH3)(O)CHPh major],
13.8 [OCH2C(CH3)(O)CHPh]. HRMS (EI): [M]+Å, found 414.1686.
C23H26O7 requires 414.1679.
4.7.2.3. 2,3-Epoxy-2-methylpropyl
2,3-di-O-benzyl-4,6-O-(S)-
benzylidene-b- -galactopyranoside 41. Two stereoisomers were
D
obtained in a 1:1 ratio (0% de). The pure diastereomeric mixture
was obtained as a syrup by column chromatography using hex-
ane–ethyl acetate (3:1) as eluent. Yield 0.5 g (90%); [a]D = +35.8
(c 1.0, CH2Cl2); MS (EI): m/z 518 (10%) [M]+Å. 1H NMR (500 MHz,
CDCl3): d 7.6–7.2 (m, 15H, 3Ph), 5.50 (s, 1H, PhCH), 4.96, 4.92
(2d, 1H, Jgem 10.8 Hz, 2-PhCHAHBO), 4.8–4.7 (m, 3H, 2-PhCHAHBO,
3-PhCH2O), 4.49, 4.44 (2d, 1H, J1,2 7.8 Hz, H-1), 4.29 (2dd, 1H,
J5,6e 1.5 Hz, J6e,6a 12.3 Hz, H-6e), 4.11 (d, 1H, J3,4 3.6 Hz, H-4),
4.05–3.80 [m, 3H, H-2, H-6a, OCHAHBC(CH3)(O)CH2], 3.7–3.5 [m,
2H, OCHAHBC(CH3)(O)CH2, H-3), 3.32 (m, 1H, H-5), 2.88, 2.73 [2d,
1H, Jgem 5.0, 4.7 Hz, OCH2C(CH3)(O)CHAHB], 2.63, 2.61 [2d, 1H,
Jgem 4.7, 5.0 Hz, OCH2C(CH3)(O)CHAHB], 1.43, 1.40 (2s, 3H, OCH2C
(CH3)(O)CH2]. 13C NMR (125 MHz, CDCl3): d 138.4–126.4 (3Ph),
103.5, 103.2 (2C-1), 101.2 (PhCH), 79.3,79.2 (2C-3), 78.4, 78.3
(2C-2) 75.3 (2-PhCH2O), 73.9 (C-4), 71.7 (3-PhCH2O), 72.0 [OCH2C
(CH3)(O)CHPh], 69.2 (C-6), 66.5 (C-5), 55.8 [OCH2C(CH3)(O)CH2],
51.7, 51.6 [2OCH2C(CH3)(O)CH2], 18.7, 18.5 [2OCH2C(CH3)(O)
CHPh]. HRMS (EI): [M]+Å, found 5518.2282. C31H34O7 requires
518.2305.
4.7.2. Epoxidation of 4,6-O-benzylidene-2,3-di-O-benzyl
derivatives
4.7.2.1. (2R)-2,3-Epoxypropyl 2,3-di-O-benzyl-4,6-O-(S)-benzyl-
idene-b-D-galactopyranoside 39. Two stereoisomers were ob-
tained in a 1.6:1 ratio (23% de).The pure diastereomeric mixture
was obtained as a solid by column chromatography using hex-
ane–ethyl acetate (3:1) as eluent. Yield 0.5 g (90%); mp 131–
132 °C; [a]
D = +52.9 (c 0.5, CH2Cl2); MS (EI): m/z 504 (10%) [M]+Å.
1H NMR (500 MHz, CDCl3): d 7.6–7.1 (m, 10H, 2Ph), 5.55 (s, 1H,
PhCH), 4.96, 4.86 (2d, 1H, Jgem 10.8 Hz, 2-PhCHAHBO), 4.81–4.76

94
J. M. Vega-Pérez et al. / Tetrahedron: Asymmetry 21 (2010) 81–95
4.7.3. Epoxidation of 4,6-O-benzylidene-3-O-benzyl derivatives
4.7.3.1. (2R)-2,3-Epoxypropyl 3-O-benzyl-4,6-O-(S)-benzyli-
dene-b-D-galactopyranoside 42. Two stereoisomers were ob-
tained in a 7.5:1 ratio (76% de). The pure diastereomeric mixture
was obtained as a solid by column chromatography using hex-
ane–ethyl acetate (1:2) as eluent. Yield 0.3 g (61%). mp 200–
CDCl3): d 138.1–126.3 (2Ph), 103.5 (C-1), 101.1 (PhCH), 79.0 (C-
3), 73.1 (C-4), 71.6 (PhCH2O), 70.1 (C-2), 69.3 (C-6), 68.5 [OCH2-
CH(O)CHCH3], 66.7 (C-5), 57.7 [OCH2CH(O)CHCH3], 52.4 [OCH2-
CH(O)CHCH3], 17.2 [OCH2CH(O)CHCH3]. HRMS (FAB): [M+Na]+,
found 451.1767. C24H28O7Na requires 451.1733. Anal. Calcd for
C24H28O7: C, 67.28; H, 6.59. Found: C, 67.02; H, 6.49.
201 °C; [
a
]D = ꢀ43.2 (c 0.5, CH2Cl2); MS (FAB): m/z 437 (70%)
[M+Na]+. 1H NMR (500 MHz, CDCl3): d 7.4–7.1 (m, 10H, 2Ph),
5.55 (s, 1H, PhCH), 4.75 (s, 2H, PhCH2O) 4.43 (d, 0.12H, J1,2
7.8 Hz, H-1 minor), 4.38 (d, 0.88H, J1,2 7.8 Hz, H-1 major), 4.31
(dd, 1H, J5,6e 1.5 Hz, J6e,6a 12.3 Hz, H-6e) 4.15 (d, 0.12H, J3,4 3.5 Hz,
H-4 minor), 4.13 (d, 0.88H, J3,4 3.5 Hz, H-4 major), 4.01–3.8 [m,
3H, OCHAHBCH(O)CH2, H-2], 3.88 (dd, 1H, J6e,6a 12.4 Hz, J5,6a
3.3 Hz, H-6a), 3.52 (dd, 0.12H, J3,4 3.4 Hz, J2,3 8.0 Hz, H-3 minor),
3.49 (dd, 0.88H, J3,4 3.5 Hz, J2,3 8.1 Hz, H-3 major), 3.38 (br s, 1H,
H-5), 3.25 [m, 1H, OCH2CH(O)CH2], 2.82 [m, 1H, OCH2CH(O)-
CHAHB], 2.77 [m, 1H, OCH2CH(O)CHAHB], 2.67 (br s, 1H, 2-OH).
13C NMR (125 MHz, CDCl3): d 138.0–126.2 (2Ph), 103.3 (C-1 major),
103.1 (C-1 minor), 101.0 (PhCH), 79.0 (C-3), 73.1 (C-4 minor), 73.0
(C-4 major), 71.6 (PhCH2O minor), 71.5 (PhCH2O major), 70.1 (C-2),
69.3 (C-6 minor), 69.2 (C-6 major), 68.9 [OCH2CH(O)CHCH3], 66.7
(C-5), 50.7 [OCH2CH(O)CH2 minor], 50.5 [OCH2CH(O)CH2 major],
44.6 [OCH2CH(O)CH2] HRMS (CI): [M+Na]+, found 413.1586.
C23H26O7Na requires 413.1576. Anal. Calcd for C23H26O7: C,
66.65; H, 6.32. Found: C, 66.60; H, 6.06.
4.7.3.4. (2S,3S)-2,3-Epoxydecyl
3-O-benzyl-4,6-O-(S)-benzyli-
dene-b- -galactopyranoside 45. Two stereoisomers were ob-
D
tained in a 13.6:1 ratio (86% de). The pure diastereomeric mixture
was obtained as a solid by column chromatography using hexane–
ethyl acetate (1.5:1) as eluent. Yield 0.4 g (80%); mp 129–130 °C;
[a]
D = +21.5 (c 1.0, CH2Cl2); MS (FAB): m/z 535 (95%) [M+Na]+. 1H
NMR (500 MHz, CDCl3): d 7.55–7.25 (m, 10H, 2Ph), 5.55 (s, 1H,
PhCH), 4.77 (s, 2H, PhCH2O), 4.43 (d, 0.07H, J1,2 7.8 Hz, H-1 minor),
4.35 (d, 0.93H, J1,2 7.8 Hz, H-1 major), 4.30 (dd, 1H, J5,6e 1.5 Hz,
J6e,6a 12.3 Hz, H-6e), 4.12 (dd, 1H, J3,4 3.6 Hz, J4,5 0.8 Hz, H-4), 4.05–
3.95 [m, 3H, H-2, H-6a, OCHAHBCH(O)CH(CH2)6CH3], 3.84 [dd, 1H
Jgem 12.2 Hz, J 3.2 Hz, OCHAHBCH(O)CH(CH2)6CH3], 3.49 (dd, 1H,
J2,3 9.7 Hz, J3,4 3.6 Hz, H-3), 3.37 (m, 1H, H-5), 2.97 [m, 2H, OCH2-
CH(O)CH(CH2)6CH3], 2.71 (s, 1H, OH), 1.6–1.2 [m, 12H, OCH2-
CH(O)CH(CH2)6CH3], 0.88 [t, 3H, J 7.0 Hz, OCH2CH(O)CH(CH2)6-
CH3]. 13C NMR (125 MHz, CDCl3): d 138.2–126.4 (2Ph), 103.5 (C-1),
101.1 (PhCH), 79.1 (C-3), 73.2 (C-4), 71.6 (PhCH2O), 70.1 (C-2),
69.3 (C-6), 68.7 [OCH2CH(O)CH(CH2)6CH3], 66.8 (C-5), 56.8, 56.4
[OCH2CH(O)CH(CH2)6CH3], 31.7, 31.6, 29.3, 29.2, 25.9, 22.6 [OCH2-
CH(O)CH(CH2)6CH3], 14.1 [OCH2CH(O)CH(CH2)6CH3]. HRMS (FAB):
[M+Na]+, found 535.2656. C30H40O7Na requires 535.2672. Anal.
Calcd for C30H40O7: C, 70.29; H, 7.86. Found: C, 70.29; H, 7.66.
4.7.3.2. (2S,3S)-2,3-Epoxy-3-phenylpropyl 3-O-benzyl-4,6-O-(S)-
benzylidene-b-D-galactopyranoside 43. Two stereoisomers were
obtained in a 6.5:1 ratio (74% de). The pure diastereomeric mixture
was obtained as a syrup by column chromatography using hexane–
ethyl acetate (1:1) as eluent. Yield 0.2 g (87.3%); [
a
]
D = ꢀ20.4 (c 0.4,
4.7.3.5. (2R)-2,3-Epoxy-2-methylpropyl 3-O-benzyl-4,6-O-(S)-
benzylidene-b-D-galactopyranoside 46. Two stereoisomers were
obtained in a 16.2:1 ratio (88% de). The pure diastereomeric
mixture was obtained as a solid by column chromatography using
hexane–ethyl acetate (1:2) as eluent. Yield 0.3 g (79%); mp 158–
CH2Cl2); MS (EI): m/z 490 (12%) [M]+Å. 1H NMR (500 MHz, CDCl3): d
7.6–7.2 (m, 15H, 3Ph), 5.55 (s, 0.87H, PhCH major), 5.54 (s, 0.13H,
PhCH minor), 4.70 (s, 2H, PhCH2O) 4.50 (d, 0.13H, J1,2 7.8 Hz, H-1
minor), 4.44 (d, 0.87H, J1,2 7.7 Hz, H-1 major), 4.33 (dd, 1H, J5,6e
1.4 Hz, J6e,6a 12.5 Hz, H-6e), 4.20 (d, 0.13H, J3,4 3.0 Hz, H-4 minor),
4.18 (d, 0.87H, J3,4 3.0 Hz, H-4 major), 4.1–3.9 [m, 4H, OCH2-
CH(O)CHPh, H-2, H-6a], 3.52 (dd, 0.13H, J3,4 3.5 Hz, J2,3 8.0 Hz, H-
3 minor), 3.49 (dd, 0.87H, J3,4 3.5 Hz, J2,3 8.1 Hz, H-3 major) 3.42
(m, 1H, H-5), 3.33 [m, 0.87H, OCH2CH(O)CHPh minor], 3.30 [m,
0.13H, OCH2CH(O)CHPh major], 2.94 [m, 0.13H, OCH2CH(O)CHPh
minor], 2.90 [m, 0.87H, OCH2CH(O)CHPh major], 2.73 (br s, 1H,
2-OH). 13C NMR (125 MHz, CDCl3): d 137.5–125.8 (3Ph), 103.5
(C-1 major), 103.2 (C-1 minor), 101.2 (PhCH), 79.2 (C-3 major),
79.1 (C-3 minor), 73.1 (C-4 mayor), 71.6 (PhCH2O), 70.1 (C-2),
69.3 (C-6 major), 69.2 (C-6 minor), 68.1 [OCH2CH(O)CHPh], 66.8
(C-5), 61.2 [OCH2CH(O)CHPh minor], 61,0 [OCH2CH(O)CHPh ma-
jor], 56.2 [OCH2CH(O)CHPh minor], 56.0 [OCH2CH(O)CHPh major].
HRMS (EI): [M]+Å, found 490.1992. C29H30O7 requires 490.1992.
159 °C; [a]D = +27.8 (c 0.5, CH2Cl2); MS (FAB): m/z 451 (100%)
[M+Na]+. 1H NMR (500 MHz, CDCl3): d 7.55–7.25 (m, 10H, 2Ph),
5.46 (s, 0.06H, PhCH minor), 5.45 (s, 0.94H, PhCH major), 4.77 (s,
2H, PhCH2O), 4.43 (d, 0.06H, J1,2 7.8 Hz, H-1 minor), 4.34 (d,
0.94H, J1,2 7.8 Hz, H-1 major), 4.29 (dd, 1H, J5,6e 1.5 Hz, J6e,6a
12.3 Hz, H-6e), 4.11 (dd, 1H, J3,4 3.6 Hz, J4,5 0.9 Hz, H-4), 4.05–
3.95 [m, 3H, H-2, H-6a, OCHAHBC(CH3)(O)CH2], 3.68 [d, 0.94H, Jgem
11.8 Hz, OCHAHBC(CH3)(O)CH2 major], 3.60 [d, 0.06H, Jgem 11.8 Hz,
OCHAHBC(CH3)(O)CH2 minor], 3.48 (dd, 1H, J2,3 9.6 Hz, J3,4 3.6 Hz,
H-3), 3.35 (m, 1H, H-5), 2.96 [d, 1H, Jgem 4.9 Hz, OCH2C(CH3)(O)-
CHAHB], 2.82 (s, 1H, OH), 2.63 [d, 1H, Jgem 4.9 Hz, OCH2C(CH3)(O)-
CHAHB], 1.38 (s, 3H, OCH2C(CH3)(O)CH2]. 13C NMR (125 MHz,
CDCl3): d 138.2–126.4 (2Ph), 103.7 (C-1), 101.1 (PhCH), 79.1 (C-
3), 73.3 (C-4), 71.6 (PhCH2O), 70.9 [OCH2C(CH3)(O)CH2], 70.1 (C-
2), 69.2 (C-6), 66.8 (C-5), 56.2 [OCH2C(CH3)(O)CH2], 51.4 [OCH2C
(CH3)(O)CH2], 18.6 [OCH2C(CH3)(O)CH2]. HRMS (FAB): [M+Na]+,
found 451.1731. C24H28O7Na requires 451.1733. Anal. Calcd for
C24H28O7: C, 67.28; H, 6.59. Found: C, 67.25; H, 6.54.
4.7.3.3. (2S,3S)-2,3-Epoxybutyl
3-O-benzyl-4,6-O-(S)-benzyli-
dene-b- -galactopyranoside 44. Two stereoisomers were ob-
D
tained in an 11.5:1 ratio (84% de). The pure diastereomeric
mixture was obtained as a solid by column chromatography using
hexane–ethyl acetate (1:1) as eluent. Yield 0.4 g (98%); mp 119–
4.7.3.6. (2S,3S)-2,3-Epoxy-2-methyl-3-phenylpropyl
3-O-ben-
120 °C; [
a]D = +15.3 (c 1.0, CH2Cl2); MS (FAB): m/z 451 (95%)
zyl-4,6-O-(S)-benzylidene-b- -galactopyranoside 47. Two ster-
D
[M+Na]+. 1H NMR (500 MHz, CDCl3): d 7.60–7.25 (m, 10H, 2Ph),
5.46 (s, 1H, PhCH), 4.76 (s, 2H, PhCH2O), 4.42 (d, 0.08H, J1,2
7.8 Hz, H-1 minor), 4.35 (d, 0.92H, J1,2 7.8 Hz, H-1 major), 4.30 (d,
1H, J6e,6a 12.4 Hz, H-6e), 4.12 (d, 1H, J3,4 3.4 Hz, H-4), 4.05–3.95
[m, 3H, H-2, H-6a, OCHAHBCH(O)CHCH3], 3.83 [dd, 0.92H Jgem
12.1 Hz, J 3.4 Hz, OCHAHBCH(O)CHCH3 major], 3.60 [dd, 0.08H Jgem
12.0 Hz, J 3.6 Hz, OCHAHBCH(O)CHCH3 minor], 3.49 (dd, 1H, J2,3
9.7 Hz, J3,4 3.5 Hz, H-3), 3.37 (m, 1H, H-5), 3.07 [m, 1H, OCH2-
CH(O)CHCH3], 2.95 [m, 1H, OCH2CH(O)CHCH3], 2.72 (s, 1H, OH),
1.33 [d, 3H, J 5.3 Hz, OCH2CH(O)CHCH3]. 13C NMR (125 MHz,
eoisomers were obtained in a 9.4:1 ratio (81% de). The pure
diastereomeric mixture was obtained as a solid by column chroma-
tography using hexane–ethyl acetate (1.5:1) as eluent. Yield 0.4 g
(85%); mp 78–79 °C; [a]D = +21 (c 1.0, CH2Cl2); MS (FAB): m/z
527 (5%) [M+Na]+. 1H NMR (500 MHz, CDCl3): d 7.6–7.2 (m, 15H,
3Ph), 5.48 (s, 1H, PhCH), 4.78 (s, 2H, PhCH2O), 4.51 (d, 0.10H, J1,2
7.8 Hz, H-1 minor), 4.43 (d, 0.90H, J1,2 7.7 Hz, H-1 major), 4.34–
4.30 [m, 2H, H-6e, OCH2C(CH3)(O)CHPh], 4.14–4.10 [m, 2H, H-4,
OCHAHBC(CH3)(O)CHPh], 4.07–4.03 (m, 2H, H-2, H-6a), 3.85 [d,
0.90H, Jgem 12.1 Hz, OCHAHBC(CH3)(O)CHPh major], 3.78 [d,

J. M. Vega-Pérez et al. / Tetrahedron: Asymmetry 21 (2010) 81–95
95
Günther, W.; Kötteritzsch, M.; Poppitz, W.; Schönecker, B. Tetrahedron Lett.
2002, 43, 2499–2503; (d) Mitra, D.; Segunpta, A.; Biradha, K.; Basak, A.
Tetrahedron: Asymmetry 2008, 19, 2678–2681.
0.90H, Jgem 11.9 Hz, OCHAHBC(CH3)(O)CHPh minor], 3.52 (dd, 1H,
J2,3 9.6 Hz, J3,4 3.5 Hz, H-3), 3.40 (m, 1H, H-5), 2.94, 2.90 (2s, 1H,
OH), 1.17 [s, 0.30H, OCH2C(CH3)(O)CHPh minor], 1.09 [s, 2.70H,
OCH2C(CH3)(O)CHPh major]. 13C NMR (125 MHz, CDCl3): d 138.2–
126.3 (3Ph), 103.9 (C-1 major), 102.6 (C-1 minor), 101.1 (PhCH),
79.1 (C-3), 73.3 (C-4), 71.6 (PhCH2O), 71.3 [OCH2C(CH3)(O)CHPh],
70.3 (C-2), 69.2 (C-6), 66.8 (C-5), 62.7 [OCH2C(CH3)(O)CHPh],
61.2 [OCH2C(CH3)(O)CHPh minor], 60.4 [OCH2C(CH3)(O)CHPh ma-
jor], 13.8 [OCH2C(CH3)(O)CHPh]. HRMS (FAB): [M+Na]+, found
527.2042. C30H32O7Na requires 527.2042. Anal. Calcd for
C30H32O7: C, 71.41; H, 6.39. Found: C, 71.29; H, 6.54.
8. (a) Charette, A. B.; Côté, B. Tetrahedron: Asymmetry 1993, 4, 2283–2286; (b)
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13. Vega-Pérez, J. M.; Periñán, I.; Vega, M.; Iglesias-Guerra, F. Tetrahedron:
Asymmetry 2008, 19, 1720–1729.
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Acknowledgements
We thank the Junta de Andalucía and the Ministerio de Educa-
ción (Spain) and the FEDER program for financial support (P06-
FQM-01885 and CTQ2007-61185). Ignacio Periñán thanks Junta
de Andalucía for a predoctoral grant.
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