Simultaneous regio- and enantiodifferentiation in carbohydrate coupling

Article abstract of DOI:10.1002/ejoc.200600125

The glycosylation of 1,2-trans-diequatorial diols derived from tetrabenzoylated and tetrabenzylated D- and L-chiro-inositol with several glycosyl donors has been investigated. An unprecedented dependence of the regioselectivity on the absolute configurati

Full text of DOI:10.1002/ejoc.200600125

FULL PAPER
DOI: 10.1002/ejoc.200600125
Simultaneous Regio- and Enantiodifferentiation in Carbohydrate Coupling
M. Belén Cid,*[b] Inés Alonso,[b] Francisco Alfonso,[a] Julia B. Bonilla,[a]
Javier López-Prados,[a] and Manuel Martín-Lomas*[a]
Dedicated to Professor J. L. García Ruano
Keywords: Density functional calculations / Glycosylation / Hydrogen bonding / Regioselectivity / Steric effect
The glycosylation of 1,2-trans-diequatorial diols derived from
tetrabenzoylated and tetrabenzylated - and -chiro-inositol
indicate that stereoelectronic factors and hydrogen bonding
between the donor and acceptor govern their relative orien-
tation and determine the regiochemical outcome of the pro-
cess. These studies also highlight the role of the acyl group
adjacent to the OH to be glycosylated in facilitating the gly-
cosylation reaction.
D
L
with several glycosyl donors has been investigated. An un-
precedented dependence of the regioselectivity on the abso-
lute configuration of the acceptor has been found. However
this trend is also modulated by the nature of the protecting
groups on both the donor and acceptor, with benzoylated ac-
ceptors affording higher levels of regioselectivity. Most of the
results have been rationalized by DFT calculations which
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
Although glycosylations crucially depend on both the
donor and acceptor,[4b] most glycosylation studies have
focused on the role of glycosyl donors in controlling the
stereoselectivity of the process. A remarkable exception is
the glycosylation with glycosylidene diazirines where the
key factor is the kinetic acidity of the acceptor OH group.
In this case, the emphasis is shifted to the role of polyol
glycosyl acceptors in controlling the regioselectivity of gly-
cosylation.[9]
As part of our work on the synthesis of inositolphos-
phoglycans (IPGs) as potential mediators in the insulin sig-
naling process, we have extensively studied the glycosylation
reactions of myo and - and -chiro inositol derivatives with
different glycosyl donors, in particular 2-azido-2-deoxy-gly-
copyranosyl trichloroacetimidates.[10] In an attempt to ex-
tend the applicability of the double stereodifferentiation
principle[11a] in glycosylation reactions[11b] we have also
studied the stereoselectivity of the glycosylation of - and
-chiro inositol derivatives with several glycosyl donors.[12]
We have now observed that when differently protected 1,2-
diols, derived from both chiro-inositol enantiomers, are
Introduction
A great deal of attention has been devoted to glycosyla-
tion reactions and a wide array of glycosylation methods,
strategies and procedures have been reported in the litera-
ture.[1,2] Established mechanistic thinking[3] and extended
experimental experience[4] emphasize the importance of
protecting groups for the effective donor-acceptor match[4b]
which determines the feasibility and the selectivity of the
glycosylation. From the first observation[5] that stereoselec-
tive 1,2-trans glycosylation can be achieved through neigh-
boring group participation,[6] careful design of protecting
groups has been used to control the reactivity of the part-
ners and the selectivity of the process.[1,7] These observa-
tions, which recently led to the reciprocal donor-acceptor
selectivity concept (RDAS),[8] constitute outstanding exper-
imental evidence of the key role of the donor-acceptor
match[4b] in governing the glycosylation outcome.
[a] Grupo de Carbohidratos, Instituto de Investigaciones Quím- used as acceptors, both the absolute configuration of the
icas, CSIC, Américo Vespucio s/n,
acceptor as well as the nature of the donor’s and acceptor’s
Isla de La Cartuja, 41092 Sevilla, Spain
protecting groups play a key role in the regiochemistry of
the coupling. A few examples of regioselective glycosyla-
tions of 1,2-cis-axial/equatorial[9,13] and 1,2-trans-diequato-
rial diols[9,10b,14] have been described and the influence of
the donor’s protecting groups on the regiochemistry of po-
lyol glycosylation has been recently investigated.[8] A no-
table example of regioselective glycosylation of a 1,2-trans-
Fax: +34-95-4460565
E-mail: manuel.martin-lomas@iiq.csic.es
[b] Departamento de Química Orgánica, Universidad Autónoma
de Madrid,
Cantoblanco 28049, Spain
Fax: +34-91-4973966
E-mail: belen.cid@uam.es
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
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M. B. Cid, M. Martín-Lomas et al.
FULL PAPER
diequatorial diol is the virtually complete regioselective gal- idate 11 under the same conditions gave a α/β mixture. Here
actosylation of the OH-4 group of p-methoxyphenyl-2-de- the 2-O-glycosylated products predominated and afforded
oxy-2-tetrachlorophthalimido-β--glucopyranoside I (see the α(1Ǟ2) pseudodisaccharide 12 as the only product in
Figure 1) using a 2,3,4-tri-O-acetyl thiophenyl galactopyr- 66% yield when the reaction temperature was decreased
anoside as glycosyl donor.[14] In this case it was also re- from –40 to –78 °C.[16] In neither case were transbenzo-
ported that OH-3 and OH-4 in I show different preferences ylation processes detected.
for fucosylation depending on the nature of the protecting
groups in the fucosyl donor. This was later observed in the
mannosylation of the diequatorial diols of methyl 4,6-O-
benzylidene-α- and -β--glucopyranoside (II and III) in the
course of RDAS studies.[8a] The glycosylation of the OH-6
group of the myo-inositol derivative IV with 2-azido-2-de-
oxy--glucopyranosyl trichloroacetimidates is another case
of regioselective glycosylation of a 1,2-trans-diequatorial
diol system IV which is frequently performed in our
laboratories for the preparation of building blocks for IPG
synthesis.[10b] There may be some other examples of suc-
cessful regioselective glycosylations of 1,2-trans-diequato-
rial diols in the course of complex glycoside and oligosac-
charide synthesis. Nevertheless, to the best of our knowl-
edge the results presented here constitute the first reported
observations and rationalization of the effect of the abso-
lute configuration and protecting groups of diol glycosyl
acceptors[15] on the regiochemistry of glycosylations.
Scheme 1. Reaction of 1L with 2, 5 and 8 and 1D with 11.
These results allowed for the straightforward syntheses
of IPG building blocks V and VI and fagopyritol B (VII)
as indicated in Figure 2 which emphasizes the different be-
havior of both enantiomers regarding the regioselectivity of
these specific glycosylations.
Figure 1. Acceptors that have shown good regioselectivities in gly-
cosilation reactions.
We have previously shown that the coupling of -chiro-
inositol terabenzoate 1L with trichloroacetimidate 2 gave a
6.4:1 mixture of the α(1Ǟ3) (3) and the α(1Ǟ2) (4) pseudo-
disaccharides in 67% combined yield (Scheme 1). Similarly,
Results and Discussion
the glycosylation of 1
L
with 5 gave a 7:1 mixture of the
In order to confirm the influence of the absolute configu-
α(1Ǟ3) (6) and the α(1Ǟ2) (7) compounds in 48% overall ration of the acceptor on the regioselectivity of these glyco-
yield.[10c] The regioselectivity was poorer but followed the sylations we have examined the reactions of 1
with 2 and
same trend in the glycosylation with the less reactive tri- 5 and 1 with 11. The results are given in Table 1 (for struc-
chloroacetimidate 8 which afforded a 2:1 mixture of the tures see Figure 3). In the glycosylations of 1 the α(1Ǟ2)
D
L
D
α(1Ǟ3) (9) and the α(1Ǟ2) (10) pseudodisaccharides in compounds (13 and 14) slightly predominated over the
78% overall yield. Interestingly, the glycosylation of the α(1Ǟ3) pseudodisaccharides (15 and 16), thus confirming
corresponding -chiro-inositol diol 1D with trichloroacetim- that the absolute configuration of the acceptor plays a role
Figure 2. Regioselective reactions of - and -chiro inositol acceptors.
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Simultaneous Regio- and Enantiodifferentiation in Carbohydrate Coupling
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in the regiochemistry of the process. Although, in these pounds with excellent yield while the reaction with 1
cases the regioselectivity was poorer than for 1 . In the gly- yielded the β(1Ǟ3) derivative 23 as the only product, albeit
cosylation of 1 with 11 a mixture of the α(1Ǟ2) (17), in lower yield.
L
L
L
β(1Ǟ2) (18) and α(1Ǟ3) (19) pseudodisaccharides was ob-
served even when the reaction was performed at –78 °C.
Thus, the tendency for the  enantiomer (1D) to form the
α(1Ǟ2) pseudodisaccharide, as observed in the glycosyla-
tion with 11, was also observed in the glycosylation with 2
and 5. However, the tendency for the  enantiomer (1L)
to form the α(1Ǟ3) glycosidic linkage, as observed in the
glycosylation with 2 and 5, was not observed in the glycosy-
lation with 11. As deduced, other factors, most likely the
nature of the protecting group at C-2 in the glycosyl donor,
also seem to be playing a role in the regiochemistry of the
process (Table 1).
Table 1. Glycosylation reactions of acceptors 1L and 1D with do-
nors 2, 5, 11 and 20. Reaction conditions: TMSOTf (0.08 equiv.),
–40 °C, diethyl ether, 1 h, –40 °C; TCA = trichloroacetimidate.
Figure 3. Structures of Table 1.
Therefore, with the only exception of the reaction of 1
L
with 11 (with a benzyloxy group in position 2), in all the
cases studied with tetrabenzoylated acceptors the regioch-
emistry of the glycosylations seems to be dictated by the
absolute configuration of the glycosyl acceptor. These re-
sults constitute the first experimental evidence of simulta-
neous regio- and enantiodifferentiation in carbohydrate
coupling.
The clear influence of the absolute configuration of the
acceptor could not be observed when a similar study was
[a] T = –78 °C. [b] Reaction time: 3 h at –40 °C, 1 h at –10 °C.
[c] Reaction time: 3 h at –40 °C. [d] Determined by 1H NMR spec-
troscopy.
carried out with the tetrabenzylated glycosyl acceptors 24
and 24 which were prepared from 1
[10c] and 1 [16] respec-
At this point, the glycosylation of 1D and 1L with trichlo- tively, as indicated in Scheme 2 for the  enantiomer. These
D
L
D
L,
roacetimidate 20, bearing a trifluoroacetamide participating syntheses required long protecting group manipulations due
group at C-2, was investigated. The results are also shown to the difficulties found when direct benzylation of the si-
in Table 1 and Figure 3. In this case, the regiochemistry of lylated tetraol -chiro-inositol derivative was tried instead
the glycosylation followed the same trend as already ob- of the benzoylation that affords 1
served for donors 2 and 5: the reaction with 1 afforded a of the glycosylation reactions with acceptors 24
5:1 mixture of the β(1Ǟ2) (21) and the β(1Ǟ3) (22) com- are presented in Table 2 and Figure 4.
D
and 1
L
.
[10c,16] The results
and 24L
D
D
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M. B. Cid, M. Martín-Lomas et al.
Table 2. Glycosylation reactions of acceptors 24 and 24 with do-
FULL PAPER
L
D
nors 2 and 5. Reaction conditions: TMSOTf (0.08 equiv.), –40 °C,
diethyl ether, 1 h, –40 °C; TCA = trichloroacetimidate.
Scheme 2. Synthesis of benzylated acceptor 24D. Reaction condi-
tions: i) a) TIPDSCl2, DMAP, DMF, imidazole, r.t., 16 h; b) BzCl,
DMAP, Py, room temp., 16 h, 36% (two steps); iii) (HF)nPy, THF,
90%; iii) 2,3-butanedione, trimethyl orthoformate, CSA, MeOH
70 °C, 5 h. 92%; iv) MeONa/MeOH 1 , MeOH/THF room temp.,
2 h, 100%; v) BnBr, NaH, tBuNH4I, DMF, 20 °C to room temp.,
12 h. 91%; vi) TFA/H2O = 9:1, room temp., 4 h, 86%.
Substituting benzoyl for benzyl groups resulted in an in-
crease of the proportions of the β anomers and small
amounts of uncharacterized pseudotrisaccharides, probably
due to the higher reactivity of the benzylated acceptors.[10e]
Compared to the results described above for 1
D, the yield
and the regioselectivity for the glycosylation of 24
D
were
similar when using donor 2 affording the α(1Ǟ2) 28 and
β(1Ǟ2) 29 pseudodisaccharides in a slightly higher pro-
portion than the α(1Ǟ3) 30 and β(1Ǟ3) 31 compounds
(C3/C2 = 1:1.5). No selectivity at all was observed with do-
nor 5 where the 1Ǟ2 (32 and 33) and the 1Ǟ3 (34 and 35) (α38 and β39 in the glycosylation with 2 and β42 in the
compounds were formed in similar proportions (C3/C2 = glycosylation with 5) and the yields were considerably de-
1.1:1). For 24
L, the regioselectivity observed in the reactions creased (Table 2 and Figure 4).
with both 2 and 5, was reversed compared to 1
L. The mix- Therefore, the nature of the protecting group in the gly-
ture of 1Ǟ2 pseudodisaccharides (α36 and β37 in the glyco- cosyl acceptor also seems to exert an important influence
sylation with 2 and α40 and β41 in the glycosylation with on the regiochemical outcome of these glycosylations.
5) predominated (C3/C2 = 1:2.5) over the 1Ǟ3 compounds While a comparison of the results obtained for 1L and 1D
Figure 4. Structures of Table 2.
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Simultaneous Regio- and Enantiodifferentiation in Carbohydrate Coupling
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under identical experimental conditions evidences the im- chiro-inositol ring) were optimized. Most of the complexes
portance of stereoelectronic factors on the regiochemistry showed a C1Ј–O2(O3) bond length around 2 Å. However,
of the process, a comparison of the behavior of 1
L
and 24
L
some slightly more stable complexes with shorter distances
also provides experimental evidence for the importance of for the incipient glycosidic bond were found. Complexes
protecting groups on the donor-acceptor match[4b] affecting obtained with 2-azide (denoted as A) and 2-methoxy (de-
the yield and the stereoselectivity but also the regioselectiv- noted as M) substituted donors and  and  acetylated ac-
ity of the coupling.
ceptors are named as AL and ML and AD and MD and
In an attempt to rationalize the above experimental re- are shown in Figure 5 and Figure 6, respectively. In each
sults, the interactions taking place in the process of glyco- case the approximation through position 2 or 3 is indicated
sidic bond formation were analyzed by means of DFT cal- by the corresponding number. Complexes obtained from 
culations.[17] Glycosyl oxocarbenium ions with 2-azide and methoxylated acceptor (denoted as LЈ) with 2-azide donor
2-methoxy groups without substituents at positions 3 and 4 are also shown in Figure 5. The equivalence between mod-
(far from the reaction center) and methyl instead of benzyl els and real systems is also indicated.
ether at position 6 were used as glycosyl donor models. The
benzoylated glycosyl acceptors were modeled by removing
the substituents at positions 5 and 6 of the cyclitol ring
and changing the benzoyl to acetyl groups. Methoxylated
glycosyl acceptors were used as models for benzylated de-
rivatives. Several nucleophile-carbonium ion complexes dif-
fering in the nucleophile orientation, acceptor configuration
( or ) and attacking OH group (OH-2 or OH-3 of the
Figure 6. Significant interactions between groups at short and long
distances [Å] determined on model complexes ML3, ML2, MD3
and MD2.
Two main interactions seem to control all these approxi-
mations. First, a very strong hydrogen bond, according to
the usual criteria,[18] which is present in all the complexes
with acetylated acceptors between the O–H group to be gly-
cosylated and the adjacent acyl group. In complexes ALЈ3
and ALЈ2 an equivalent but weaker interaction is also pres-
ent with the adjacent methoxy group. Second, an important
hydrogen bond between C1Ј and the closest O2(O3) –H
group, the directionality of which determines the conforma-
tion (especially Φ angle) of the pseudodisaccharide being
formed. This interaction is present in all the complexes ex-
cept in AD2 and MD2 where there is an equivalent interac-
tion between C5Ј–H and O3.
Comparing the hydrogen bond between the O3(O2)–H
bond and the adjacent acyl group in complexes with acety-
lated acceptors, with respect to the situation in the acceptor
model, the hydrogen atom seems to be partially transferred
to the carbonyl group.[19] NBO analyses[20] show an impor-
tant charge donation from a lone pair of the carboxylic oxy-
gen to the O–H antibonding orbital that weakens this bond
Figure 5. Significant interactions between groups at short and long
distances [Å] determined on model complexes AL3, AL2, AD3,
AD2, ALЈ3 and ALЈ2.
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M. B. Cid, M. Martín-Lomas et al.
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(Wiberg bond indexes of O–H bonds involved in glycosidic was present in AL3 (the equivalent distance O–HC5Ј with
bond formation are in the range 0.50–0.52 whereas the val- the OMe group in ALЈ3 is 3.72 Å). The possible steric hin-
ues for the other O–H group are in the range 0.65–0.66).[21] drance in ALЈ2 would decrease (distance between axial H6
The second-order perturbational energy associated with and C5Ј = 5.54 Å) with respect to the situation in AL2
these stabilizing donations are in the range 43–46 kcal/mol, (4.70 Å). These facts agree with the reverse regioselectivity
a big value compared with the interactions found for the experimentally observed for benzylated acceptors (see the
other O–H groups (7–12 kcal/mol) that participate in a nor- results of the reaction of 24
L with 2 and 5 in Table 2).
mal hydrogen bond. This suggests that glycosylation may be On the other hand, in the case of the acceptor with 
assisted by the basic character of the adjacent acyl group. In configuration, complex AD3 also shows a stabilizing inter-
agreement with this, when the acyl groups in complexes action (analogous to the one found in AL3) between the 4-
AL3 and AL2 were substituted by methyl groups (see com- acyl group and in this case C3Ј–H (distance C=O–HC3Ј
plexes ALЈ3 and ALЈ2 in Figure 5) the complexation pro- 2.43 Å). However due to the orientation of this acyl group
cess was less favorable and a slight elongation of the dis- steric effects should become important when the size of the
tances C1Ј–O3(O2) (1.67 and 1.68 Å) and C1ЈH–O2(O3) acyl group increases (distance COCH3–HC3Ј 3.71 Å). The
(2.29 and 2.10 Å) was observed. Although there also exists approximation shown for complex AD2 is almost totally
an interaction between the O–H group to be glycosylated free of steric interactions but does not present any ad-
and the adjacent methoxy group, this must be weaker ac- ditional favourable electronic interactions. The experimen-
cording to the values of the distances and angles.[18]
Complexes shown in each Figure are quite similar in en-
ergy (see supporting information) and do not seem to have
tal result in this case is poor regioselectivity (see reaction of
1
D
with 2 and 5 in Table 1).
In order to study the role of the group at C-2 of the
important differences in electronic interactions. However, a glycosyl donor, complexes shown in Figure 5 and Figure 6
careful analysis of these structures may help to understand must be compared. Both types of complexes are quite sim-
most of the experimental results presented in Tables 1 and ilar. However, there exists a remarkable difference between
2. First, the high regioselectivity to position 3 shown by complex AL3 and ML3 regarding the orientation of the C-
acceptor 1
and 5, which is inverted to position 2 with benzylated ac- C2Ј–O–CH3 = 155.4°].[22] Probably with this orientation the
ceptor 24 and the same donors. Second, the low regioselec- nitrogen atom on the azide group can avoid electronic re-
tivity observed for acceptor 1 with 2-azide substituted do- pulsion with O2, whereas the methoxy group cannot reach
L in reaction with 2-azide substituted donors 2 2 substituent [torsion angles: C1Ј–C2Ј–N–N = 92.7°; C1Ј–
L
D
nors 2 and 5. Third, the role of the group at C-2 of the this conformation due to steric reasons. The different con-
glycosyl donor: azide group induces high 3-regioselectivity formation of the C-2 substituent causes a dramatic decrease
with acceptor  whereas the benzyloxy group induces high in the value of ΦO5Ј–C1Ј–O3–C3 from 93.8° in complex AL3
2-regioselectivity with acceptor .
to 60.2°[23] in complex ML3. Thus, complex ML3 shows an
The interactions that take place during the approach of orientation similar to ML2 (and also to AL2, compare Φ
the acceptor to the lower face of the donor can be related angle values in Figure 5 and Figure 6) and therefore they
to the value of the dihedral angle Φ as well as to the dis- should present similar interactions between the axial sub-
tances between certain groups indicated in Figures 5 and 6. stituent at C-5 in ML3 and C-6 in ML2 and AL2 of the
In order to analyze the results from the AL3 and AL2 acceptor and the lower face of the donor. Additionally,
approximations (see Figure 5), it must be mentioned that in ML3 shows the 4-acyl group inside the lower face of the
complex AL2, the axial substituent at C-6 of the acceptor donor (distances C=O–HC5Ј 2.76 and C=O–HC3Ј 2.58 Å)
(that has been eliminated in the model) should be closer to and thus the stabilizing interaction should be smaller than
the lower face of the donor (distance H6–HC5Ј 4.70 Å) in complex AL3. Therefore, with these 2-methoxy ML com-
than in complex AL3 where the closest substituent, at C- plexes no regioselectivity should be expected as can be ex-
5 in this case, shows a longer distance (H5–HC5Ј 6.26 Å). perimentally observed in the reaction of 1
L with 11
Additionally, complex AL3 shows a stabilizing interaction (Table 1). For the  enantiomer the approximation through
between the 4-acyl group and C5Ј–H (distance C=O–HC5Ј OH-2 seems to be slightly favored according to the distance
2.43 Å). These factors would afford a high C3/C2 ratio of the incipient bond (1.66 Å in complex MD2 vs. 1.68 Å
which is in agreement with experimental results (see highly in complex MD3). The relatively unfavorable situation in
regioselective reactions of 1
L
with 2 and 5, Table 1).
MD3 may also be ascribed to steric factors. The distance
When methoxylated glycosyl acceptors were used an between methyl groups of the C2Ј-methoxy substituent and
increase in the dihedral angle Φ was observed. Thus, the 4-acetyl is only 3.68 Å. In comparison with AD3, the
dihedral angle ΦO5Ј–C1Ј–O3–C3 increased from 93.8 (in AL3) COCH3–HC3Ј distance in MD3 is 3.64 Å. Most likely the
to 104.0° (in ALЈ3) (see Figure 5). In the case of influence of these effects on the regioselectivity of the glyco-
approximation through position 2 the dihedral angle sylation will increase as the size of the substituent at the 2-
ΦO5Ј–C1Ј–O2–C2 varied from 67.6° (in AL2) to 73.8° (in position of the glycosyl donor increases.
ALЈ2). These variations provide fewer interactions between
These calculations have highlighted the importance of
groups on the acceptor and the lower face of the donor in hydrogen bonds on the acceptor residue in the regiochem-
both ALЈ complexes. The absence of the carbonyl group in ical outcome of the glycosylation of diol acceptors. Particu-
ALЈ3 produces the loss of the stabilizing interaction that larly interesting is the assistance of an acyl group close to
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Simultaneous Regio- and Enantiodifferentiation in Carbohydrate Coupling
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benzyl-2-deoxy-
D
-glucopyranosyl-α(1Ǟ3)-1,4,5,6-tetra-O-benzoyl-
the hydroxy group to be glycosylated. This effect can help
to explain the results presented herein as well as some
others already described in the bibliography. For example,
the regioselectivity in the glycosylation of a 3,4-diol of a
glucuronic derivative in a 1C4 conformation.[24] In this case,
glycosylation at the 3-position is facilitated by the meth-
oxycarbonyl group at the 6-position. The higher ratio of
glycosylation at C2 of the 2,4-mannosyl diol acceptors,
when a benzoyl group is at C3 compared with a benzyl
group, is also in agreement with these observations.[15]
As can be seen in complexes ALЈ3 and ALЈ2 the hydro-
gen bond assistance can also be found, although to a lesser
extent, with alkoxy substituents. This effect could explain
the lower degree of glycosylation of hydroxy groups with
either no possible or favorable hydrogen bond assistance
D
-chiro-inositol (15): A mixture of 3,4,6-tri-O-benzyl-2-deoxy-α--
glucopyranosyl trichloroacetimidate (2) (296.0 mg, 0.477 mmol)
and 1,4,5,6-tetra-O-benzoyl--chiro-inositol (1 ) (237.5 mg,
D
0.398 mmol) was co-evaporated 3 times with toluene, 4-Å molecu-
lar sieves were added and the residue was dried under vacuum over-
night. The mixture was dissolved in dry ether (15 mL) in an argon
atmosphere and stirred at room temperature for 30 min, then 0.08
equiv. (318 µL of a 0.1  solution) of TMSOTf was added at –40 °C
and the reaction mixture stirred for 1 h at –40 °C. Then it was
quenched with Et3N, concentrated and purified by flash
chromatography (toluene/acetone, 40:1) to yield 167 mg (40%) of
pseudodisaccharide 13 and 113 mg (27%) of pseudodisaccharide
15.
Data of the α(1Ǟ2) Pseudodisaccharide 13: [α]2D0 = +86.4 (c = 0.7,
CHCl3).1H NMR (500 MHz, CDCl3): δ = 8.17–7.76 (m, 8 H, Hor-
described in the literature. That could be the case of the tho), 7.64–7.05 (m, 15 H, Bn and 12 H, Bz), 6.00–5.95 (m, 2 H, H4
and H6), 5.93 (br. t, J = 3.5 Hz, 1 H, H1), 5.87 (dd, J = 10.4 and
higher ratio of glycosylation of hydroxy groups at C3-posi-
tions, even being the most hindered one, compared to OH-
3.1 Hz, 1 H, H5), 5.22 (d, J = 3.6 Hz, 1 H, H1Ј), 4.71–4.39 (3 AB
systems, 6 H, 3CH2Ph), 4.44 (m, 1 H, H3), 4.34 (dd, J = 9.5 and
2 in α-altrose diol acceptor derivatives described by Fraser-
3.4 Hz, 1 H, H2), 4.10 (m, 1 H, H5Ј), 3.80 (t, J = 9.9 Hz, 1 H, H3Ј),
Reid and collaborators.[8b] This fact could also explain the
3.62 (d, J = 3.2 Hz, 2 H, H6Ј), 3.57 (t, J = 9.8 Hz, 1 H, H4Ј) and
low glycolysation tendency of the axial hydroxy group at
3.37 (d, J = 10.0 and 3.6 Hz, 1 H, H2Ј) ppm. 13C NMR (125 MHz,
C1 vs. C2 in -chiro-inositol 1,2-syn diol acceptors.[10c]
CDCl3): δ = 166.6, 165.8, 165.3 and 165.0 (4CO), 138.2, 138.0 and
137.8 (3C, Bn), 134.1, 133.9, 133.6 and 133.5 (4CHpara), 130.3–
127.9 (15CH, Bn and 16CH, Bz), 129.6, 129.5, 129.2 and 129.1
(4C, Bz), 96.6 (C1Ј), 80.4 (CH), 78.3 (CH), 76.9 (CH), 75.6
(CH2Ph), 75.1 (CH2Ph), 73.8 (CH2Ph), 72.6 (CH), 71.7 (CH), 71.6
(CH), 70.2 (CH), 68.9 (CH), 68.6 (CH2), 67.8 (CH) and 63.8 (CH)
ppm. C61H55O14N3 (1054.12): calcd. C 69.50 %, H 5.25 %, N 3.98
%; found: C 69.00 %, H 5.43 %, N 3.73 %. FAB HRMS calcd. for
[C61H55O14N3+Na]+: 1076.3581, found: 1076.3545.
Conclusions
In summary, we have presented experimental evidence
for the simultaneous regio- and enantiodifferentiation in the
glycosylation of 1,2-trans-diequatorial diol systems and for
the influence of protecting groups, of both donor and ac-
ceptor partners on the regioselectivity of these processes.
DFT calculations indicate that this regioselectivity is gov-
erned by stereoelectronic factors and predicts that an acyl
group adjacent to the OH to be glycosylated facilitates the
glycosylation itself. According to these studies, the trend of
glycosylation of a determined hydroxy group could be mod-
ulated by the nature of the protecting groups close to the
reaction centre, both those located on the donor and on the
acceptor partners.
Data of the α(1Ǟ3) Pseudodisaccharide 15: [α]2D0 = +56.4 (c = 0.7,
CHCl3). 1H NMR (500 MHz, CDCl3): δ = 8.15–7.76 (m, 8 H, Hor-
tho), 7.65–7.10 (m, 15 H, 3Bn and 12 H, 4Bz), 6.08 (t, J = 10.3 Hz,
1 H, H4), 5.91 (t, J = 3.6 Hz, 1 H, H6), 5.82 (dd, J = 10.3 and
3.3 Hz, 1 H, H5), 5.79 (t, J = 3.6 Hz, 1 H, H1), 5.04 (d, J = 3.6 Hz,
1 H, H1Ј), 4.80–4.38 (3 AB systems, 6 H, 3CH2Ph), 4.30 (m, 1 H,
H2), 4.23 (m, 1 H, H5Ј), 4.18 (t, J = 9.3 Hz, 1 H, H3), 3.95 (t, J =
9.7 Hz, 1 H, H3Ј), 3.81 (d, J = 4.4 Hz, 1 H, C2OH), 3.60 (dd, J =
10.4 and 2.0 Hz, 1 H, H6aЈ), 3.53 (dd, J = 10.4 and 5.7 Hz, 1 H,
H6bЈ), 3.47 (t, J = 9.7 Hz, 1 H, H4Ј), 3.37 (dd, J = 9.8 and 3.7 Hz,
1 H, H2Ј) ppm. 13C NMR (125 MHz, CDCl3): δ = 166.0, 165.8,
165.4 and 165.1 (4CO), 137.9, 137.8 and 137.6 (3C, Bn), 134.0,
133.9, 133.6 and 133.2 (4CHpara), 130.4–128.1 (15CH, Bn and
16CH, Bz), 129.6, 129.4, 129.2 and 129.2 (4C, Bz), 99.9 (C1Ј), 83.5
(C3), 80.9 (CH), 78.5 (CH), 76.0 (CH2Ph), 75.5 (CH2Ph), 73.9
(CH2Ph), 72.1 (CH), 70.9 (CH), 70.7 (CH), 70.4 (CH), 70.1 (CH),
68.8 (CH), 68.6 (CH2) and 64.2 (CH) ppm. FAB HRMS calcd. for
[C61H55O14N3+Na]+: 1076.3581, found: 1076.3612.
Experimental Section
General Remarks: Diethyl ether and dichloromethane were distilled
from sodium benzophenone and calcium hydride, respectively. Mo-
lecular sieves (4 Å, powdered) were dried in the oven at 100 °C and
activated for 5 min under vacuum at 500 °C. All reactions were run
in an atmosphere of dry argon using oven-dried glassware and
freshly distilled and dried solvents unless otherwise stated. TLC
was performed using silica gel GF254. Silica gel (230–400 mesh) was
used for flash chromatography and eluents are given as volume to
volume ratios (v/v). All aqueous solutions were saturated unless
otherwise stated. 1H NMR (300, 400 and 500 MHz) and 13C NMR
(125 and 75 MHz) spectra were recorded at 25 °C in CDCl3 unless
otherwise noted, chemical shifts are given in ppm relative to CDCl3
(δ = 7.27 ppm) and coupling constants are reported in Hz. Reso-
nances were assigned by means of 2D spectra (COSY, HMQC and
HSQC).
2-Azido-3,4,6-tri-O-benzyl-2-deoxy-
1,4,5,6-tetra-O-benzoyl- -chiro-inositol (14), 2-Azido-3,4,6-tri-O-
benzyl-2-deoxy- -galactopyranosyl-α(1Ǟ3)-1,4,5,6-tetra-O-benzoyl-
-chiro-inositol (16): These pseudodisaccharides were prepared
D-galactopyranosyl-α(1Ǟ2)-
D
D
D
from 3,4,6-tri-O-benzyl-2-deoxy-α--galactopyranosyl trichlo-
roacetimidate (5) (74 mg, 0.12 mmol) and 1,4,5,6-tetra-O-benzoyl-
-chiro-inositol (1D) (60 mg, 0.10 mmol) as described for the prepa-
ration of 13 and 15, by addition of 0.08 equiv. (80 µL of 0.1  solu-
tion) of TMSOTf at –40 °C in dry ether (3.5 mL) and by stirring
the reaction mixture for 1 h at –40 °C; yield after flash chromatog-
raphy (toluene/acetone, 40:1) 35 mg (33%) of pseudodisaccharide
14 and 31 mg (29%) of pseudodisaccharide 16.
2-Azido-3,4,6-tri-O-benzyl-2-deoxy-
1,4,5,6-tetra-O-benzoyl- -chiro-inositol (13), 2-Azido-3,4,6-tri-O-
D-glucopyranosyl-α(1Ǟ2)-
D
Eur. J. Org. Chem. 2006, 3947–3959
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3953

M. B. Cid, M. Martín-Lomas et al.
FULL PAPER
Data of the α(1Ǟ2) Pseudodisaccharide 14: [α]2D0 = +80.9 (c = 1.0,
CHCl3). 1H NMR (500 MHz, CDCl3): δ = 8.16–7.76 (m, 8 H, Hor-
tho), 7.65–7.15 (m, 15 H, 3Bn and 12 H, 4Bz), 5.98–5.94 (m, 2 H,
H4, H6), 5.92 (br. t, J = 3.5 Hz, 1 H, H1), 5.85 (dd, J = 10.4 and
3.3 Hz, 1 H, H5), 5.20 (d, J = 3.6 Hz, 1 H, H1Ј), 4.80–4.34 (3 AB
systems, 6 H, 3CH2Ph), 4.41 (m, 1 H, H3), 4.32 (dd, J = 9.5 and
3.4 Hz, 1 H, H2), 4.15 (m, 1 H, H5Ј), 3.89 (dd, J = 10.4 and 3.6 Hz,
1 H, H2Ј), 3.75 (m, 2 H, H3Ј and H4Ј), 3.59 (d, J = 4.4 Hz, 1 H,
C3OH), 3.51 (dd, J = 9.5 and 7.1 Hz, 1 H, H6aЈ) and 3.32 (dd, J =
6.01 (t, J = 10.5 Hz, 1 H, H4), 5.93 (t, J = 3.5 Hz, 1 H, H6), 5.84
(t, J = 3.5 Hz, 1 H, H1), 5.79 (dd, J = 10.5 and 3.5 Hz, 1 H, H5),
5.13 (d, J = 4.0 Hz, 1 H, H1Ј), 4.83 (d, J = 11.5 Hz, 1 H, CH2Ph),
4.81 (d, J = 11.5 Hz, 1 H, CH2Ph), 4.70 (d, J = 11.5 Hz, 1 H,
CH2Ph), 4.56 (AB system, 2 H, CH2Ph), 4.50 (d, J = 11.5 Hz, 1
H, CH2Ph), 4.45 (br. t, J = 10.0 Hz, 1 H, H3), 4.40 (AB system, 2
H, CH2Ph), 4.16 (dd, J = 9.5 and 3.0 Hz, 1 H, H2), 4.06 (dd, J =
4.0 and 10.0 Hz, 1 H, H2Ј), 4.05 (s, 1 H, OH), 4.03 (br. t, J =
7.0 Hz, 1 H, H5Ј), 3.90 (br. s, 1 H, H4Ј), 3.79 (dd, J = 10.0 and
9.5 and 5.3 Hz, 1 H, H6bЈ) ppm.13C NMR (125 MHz, CDCl3): δ = 2.5 Hz, 1 H, H3Ј), 3.54 (t, J = 8.5 Hz, 1 H, H6aЈ), 3.50 (dd, J = 6.0
166.6, 165.8, 165.1 and 165.0 (4CO), 138.3, 137.8 and 137.7 (3C,
and 9.0 Hz, 1 H, H6bЈ) ppm. 13C NMR (CDCl3, 125 MHz): δ =
Bn), 134.1, 133.9, 133.6 and 133.5 (4CHpara), 130.3–128.1 (15CH, 166.0, 1656, 164.8, 164.7 (CO, Bz), 138.6, 138.3, 138.1, 137.5 (C,
Bn and 16CH, Bz), 129.7, 129.6, 129.2 and 129.0 (4C, Bz), 97.8
Bn), 133.69, 133.65, 133.2, 133.1 (CHpara, Bz), 130.0, 129.9, 129.8,
(C1Ј), 77.9 (CH), 77.7 (CH), 74.9 (CH2Ph), 73.8 (CH2Ph), 73.7 129.7 (CHortho, Bz), 129.6, 129.3, 128.93, 128.88 (C, Bz), 128.73,
(CH), 72.8 (CH2Ph), 72.6 (CH), 71.7 (CH), 71.0 (CH), 70.3 (CH), 128.67, 128.5, 128.4, 128.33, 128.27, 128.2, 127.9, 127.7, 127.52,
69.4 (CH2), 68.8 (CH), 68.5 (CH) and 60.1 (CH) ppm. FAB HRMS 127.48, 127.4 (CH, Bn and Bz), 102.1 (C1Ј), 80.5 (C2), 79.4 (C3Ј),
calcd. for C61H55O14N3+Na+: 1076.3581, found: 1076.3621.
75.8 (C2Ј), 74.7 (CH2), 74.4 (CH2, C4Ј), 73.2 (CH2), 72.4 (CH2),
71.6 (C3 and C4), 70.1 (C1, C5), 69.9 (C5Ј), 68.8 (C6), 68.0 (C6Ј)
ppm. FAB HRMS calcd. for [C68H62O15+Na]+: 1141.3981, found:
1141.3953, calcd. for C68H62O15+K: 1157.3720, found: 1157.3705.
Data of the α(1Ǟ3) Pseudodisaccharide 16: [α]2D0 = +59.8 (c = 0.5,
CHCl3). 1H NMR (500 MHz, CDCl3): δ = 8.11–7.76 (m, 8 H, Hor-
tho), 7.65–7.10 (m, 15 H, Bn and 12 H, Bz), 6.09 (t, J = 9.7 Hz, 1
H, H4), 5.90 (t, J = 3.6 Hz, 1 H, H6), 5.78 (dd, J = 9.6 and 3.5 Hz,
1 H, H5), 5.74 (t, J = 3.6 Hz, 1 H, H1), 5.11 (d, J = 3.8 Hz, 1 H,
H1Ј), 4.80–4.20 (3 AB systems, 6 H, 3CH2Ph), 4.32 (m, 1 H, H5Ј),
4.28 (m, 1 H, H2), 4.25 (t, J = 9.7 Hz, 1 H, H3), 3.90 (dd, J = 10.6
and 2.7 Hz, 1 H, H3Ј), 3.85 (dd, J = 10.6 and 3.8 Hz, 1 H, H2Ј),
3.80 (s, 1 H, H4Ј), 3.76 (d, J = 6.05 Hz, 1 H, C2), 3.48 (dd, J = 9.5
and 8.1 Hz, 1 H, H6aЈ), 3.22 (dd, J = 9.5 and 4.0 Hz, 1 H, H6bЈ)
ppm. 13C NMR (125 MHz, CDCl3): δ = 166.1, 165.8, 165.3 and
165.1 (4CO), 138.2, 137.9 and 137.5 (3C, Bn), 134.0, 133.9, 133.6
and 133.3 (4CHpara), 130.4–127.9 (15CH, Bn and 16CH, Bz),
129.4, 129.3, 129.2 and 129.1 (4C, Bz), 99.9 (C1Ј), 81.6 (CH), 78.5
(CH), 74.8 (CH2Ph), 73.8 (CH2Ph), 73.7 (CH), 73.0 (CH2Ph), 71.3
(CH), 71.1 (CH), 71.1 (CH), 70.4 (CH), 69.9 (CH), 69.8 (CH2),
68.8 (CH) and 60.4 (CH) ppm. FAB HRMS calcd. for
[C61H55O14N3+Na]+: 1076.3581, found: 1076.3598.
Data for Pseudodisaccharide β(1Ǟ2) 18: TLC, toluene/AcOEt =
1
9:1, Rf = 0.38. [α]2D0 = –57.6 (c = 0.5, CHCl3). H NMR (CDCl3,
500 MHz): δ = 8.12 (d, J = 7.5 Hz, 2 H, Hortho), 8.04 (d, J =
7.5 Hz, 2 H, Hortho), 8.03 (d, J = 7.5 Hz, 2 H, Hortho), 7.77 (d, J
= 8.0 Hz, 2 H, Hortho), 7.64–7.15 (m, 20 H, Bn and 12 H, Bz),
6.04 (t, J = 10.0 Hz, 1 H, H4), 5.93 (m, 2 H, H1, H6), 5.82 (br. d,
J = 10.5 Hz, 1 H, H5), 4.85 (d, J = 11.5 Hz, 1 H, CH2Ph), 4.78 (d,
J = 11.5 Hz, 1 H, CH2Ph), 4.72 (s, 1 H, OH), 4.68 (AB system, 2
H, CH2Ph), 4.59 (d, J = 11.0 Hz, 1 H, CH2Ph), 4.55 (d, J = 8.0 Hz,
1 H, H1Ј), 4.53 (d, J = 12.0 Hz, 1 H, CH2Ph), 4.48 (br. t, J =
9.5 Hz, 1 H, H3), 4.32 (AB system, 2 H, CH2Ph), 4.25 (br. d, J =
9.5 Hz, 1 H, H2), 3.79 (br. s, 1 H, H4Ј), 3.78 (t, J = 9.0 Hz, 1 H,
H2Ј), 3.63 (t, J = 6.0 Hz, 1 H, H5Ј), 3.58 (dd, J = 9.0 and 6.5 Hz,
1 H, H6aЈ), 3.50 (dd, J = 10.0 and 3.0 Hz, 1 H, H3Ј), 3.36 (dd, J =
9.5 and 5.5 Hz, 1 H, H6bЈ) ppm. 13C NMR (CDCl3, 125 MHz): δ
= 166.0, 165.6, 164.8, 164.6 (CO, Bz), 138.1 (3C, Bn), 137.3 (C,
Bn), 133.7, 133.6, 133.1, 133.0 (CHpara, Bz), 130.1, 130.0, 129.84
(CHortho, Bz), 129.83 (C, Bz), 129.7 (CHortho, Bz), 129.1, 128.93,
128.86 (C, Bz), 128.7, 128.64, 128.41, 128.38, 128.36, 128.3, 128.2,
128.1, 127.8, 127.7, 127.6, 127.5 (CH Bn and Bz), 105.2 (C1Ј), 82.5
(C3), 82.1 (C3Ј), 78.9 (C2Ј), 75.4 (CH2), 74.6 (CH2), 74.0 (C5Ј), 73.7
(CH2), 73.3 (CH2), 73.0 (C4Ј), 71.8 (C4), 70.96 (C2), 70.05 (C5),
70.00 (C1), 68.7 (C6Ј), 68.6 (C6) ppm. FAB HRMS calcd. for
[C68H62O15+H]+: 1119.4167, found: 1119.4156.
2,3,4,6-Tetra-O-benzyl-
benzoyl- -chiro-inositol (17), 2,3,4,6-Tetra-O-benzyl-
anosyl-β(1Ǟ2)-1,4,5,6-tetra-O-benzoyl- -chiro-inositol (18) and
2,3,4,6-Tetra-O-benzyl- -galactopyranosyl-α(1Ǟ3)-1,4,5,6-tetra-O-
benzoyl- -chiro-inositol (19): These pseudodisaccharides were pre-
D-galactopyranosyl-α(1Ǟ2)-1,4,5,6-tetra-O-
L
D
-galactopyr-
L
D
L
pared from 2,3,4,6-tetra-O-benzyl--galactopyranosyl trichloroace-
timidate (11) (100 mg, 0.146 mmol) and 1,4,5,6-tetra-O-benzyl--
chiro-inositol (1L) (87 mg, 0.146 mmol) as described for the prepa-
ration of 13 and 15 by addition of 0.08 equiv. (117 µL of 0.1 
solution) of TMSOTf at –40 °C in dry ether (3.7 mL) and stirring
the reaction mixture for 1 h at –40 °C. The crude product was puri-
fied by preparative TLC (hexane/AcOEt = 3:1) to separate the re-
sulting trichloroacetamide (26 mg, Rf = 0.79 in hexane/AcOEt =
Data for Pseudodisaccharide α(1Ǟ3) 19: TLC, toluene/AcOEt =
1
9:1, Rf = 0.54. [α]2D0 = –28.6 (c = 0.8, CHCl3). H NMR (CDCl3,
500 MHz): δ = 8.19 (d, J = 7.5 Hz, 2 H, Hortho), 8.07 (d, J =
7.5 Hz, 2 H, Hortho), 7.92 (d, J = 8.0 Hz, 2 H, Hortho), 7.73 (d, J
= 7.5 Hz, 2 H, Hortho), 7.70–7.04 (m, 20 H, Bn and 12 H, Bz),
6.00 (t, J = 10.0 Hz, 1 H, H4), 5.92 (t, J = 3.5 Hz, 1 H, H6), 5.87
(t, J = 3.5 Hz, 1 H, H1), 5.77 (dd, J = 10.5 and 3.0 Hz, 1 H, H5),
5.23 (s, 1 H, OH), 4.86 (d, J = 12.0 Hz, 1 H, CH2Ph), 4.85 (br. s,
1 H, H1Ј), 4.80 (d, J = 11.0 Hz, 1 H, CH2Ph), 4.72 (AB system, 2
H, CH2Ph), 4.67 (d, J = 12.0 Hz, 1 H, CH2Ph), 4.44 (br. dd, J =
9.5 and 3.5 Hz, 1 H, H2), 4.42 (d, J = 11.0 Hz, 1 H, CH2Ph), 4.13
(t, J = 9.5 Hz, 1 H, H3), 4.03 (m, 3 H, H2Ј, H3Ј, H4Ј), 4.02 (AB
system, 2 H, CH2Ph), 3.94 (dd, J = 9.5 and 4.5 Hz, 1 H, H5Ј), 3.22
(t, J = 9.0 Hz, 1 H, H6aЈ), 2.60 (dd, J = 9.0 and 4.5 Hz, 1 H, H6bЈ)
ppm. 13C NMR (CDCl3, 125 MHz): δ = 165.6, 165.4, 165.0, 164.7
(CO, Bz), 138.7, 138.3, 138.0, 137.0 (C, Bn), 133.6, 133.5, 133.13,
2:1) and the remaining acceptor 1L (22 mg, 25%, Rf = 0.05 in hex-
ane/AcOEt = 2:1). Products with intermediate Rf values were repu-
rified by preparative TLC (toluene/AcOEt, 95:5) to yield pseudodi-
saccharides α(1–2) 17 (40 mg, 24%), β(1–2) 18 (11 mg, 7%) and
α(1–3) 19 (33 mg, 20%) as colourless syrups. When the reaction
was carried out at –78 °C for 2 h, trichloroacetamide (14 mg), the
remaining acceptor 1L (16 mg, 10%) and disaccharides α(1–2) 17
(40 mg, 24%), β(1–2) 18 (10 mg, 6%) and α(1–3) 19 (35 mg, 21%)
were obtained.
Data for the α(1–2) Pseudodisaccharide 17: TLC, toluene/AcOEt =
1
9:1, Rf = 0.42. [α]2D0 = –20.7 (c = 1.0, CHCl3). H NMR (CDCl3,
500 MHz): δ = 8.14 (d, J = 7.5 Hz, 2 H, Hortho), 8.03 (d, J = 133.08 (CHpara, Bz), 130.02, 129.95, 129.86, 129.6 (CHortho, Bz),
7.0 Hz, 2 H, Hortho), 8.02 (d, J = 8.0 Hz, 2 H, Hortho), 7.78 (d, J 129.6, 129.4, 129.0, 128.9 (C, Bz), 128.8, 128.7, 128.4, 128.3, 128.2,
= 7.5 Hz, 2 H, Hortho), 7.67–7.15 (m, 20 H, Bn and 12 H, Bz),
128.14, 128.10, 127.8, 127.62, 127.58, 127.4, 127.3 (CH, Bn and
3954
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 3947–3959

Simultaneous Regio- and Enantiodifferentiation in Carbohydrate Coupling
FULL PAPER
Bz), 102.9 (C1Ј), 84.0 (C3), 79.2 (C3Ј), 75.9 (C2Ј), 74.9, 74.6 disaccharide (29 mg, 0.028 mmol, 30 %) was prepared from 20
(CH2Ph), 74.1 (C4Ј), 73.0, 72.3 (2CH2Ph), 71.0 (C4), 70.7 (C5), 70.6
(60 mg, 0.106 mmol, 1.2 equiv.) and 1 (55 mg, 0.092 mmol,
L
(C2), 69.9 (C5Ј), 69.7 (C1), 68.6 (C6), 67.0 (C6Ј) ppm. FAB HRMS 1 equiv.) as described for the preparation of 13 and 15 by addition
calcd. for [C68H62O15+Na]+: 1141.3981, found: 1141.3983, calcd.
for [C68H62O15+K]+: 1157.3720, found: 1157.3718.
of 41 µL (0.08 equiv.) of a solution 0.2  of TMSOTf at –40 °C in
dry ether (3 mL) and stirring the reaction mixture for 30 h at
–40 °C, then additionally for 1 h at –10 °C. The suspension was
filtered through a short pad of celite, the solvent evaporated under
vacuum to provide a residue which was separated by flash
chromatography (hexane/AcOEt = 3:1, then 2:1, 1:1, AcOEt).
[α]2D0 = –68.2 (c = 0.67, CHCl3). 1H NMR (CDCl3, 500 MHz): δ =
8.09 (d, J = 7.5 Hz, 2 H, Hortho), 8.03 (d, J = 7.5 Hz, 2 H, Hortho),
8.01 (d, J = 8.5 Hz, 2 H, Hortho), 7.78 (d, J = 7.5 Hz, 2 H, Hortho),
7.64, 7.63 (2t, J = 7.5 Hz, 2 H, Hpara), 7.53 (t, J = 7.5 Hz, 2 H,
Hmeta), 7.51 (t, J = 7.5 Hz, 1 H, Hpara), 7.50 (t, J = 7.5 Hz, 2 H,
Hmeta), 7.39 (t, J = 7.5 Hz, 1 H, Hmeta), 7.37 (m, 2 H, Hmeta,
Hpara), 7.24 (t, J = 7.5 Hz, 2 H, Hmeta), 6.97 (d, J = 8.0 Hz, 1 H,
NHCOCCl3), 6.02 (m, 1 H, H4), 5.87 (m, 1 H, H6), 5.85(m, 1 H,
H5), 5.82 (m, 1 H, H1), 5.51 (t, J = 9.5 Hz, 1 H, H3Ј), 5.17 (d, J =
8.5 Hz, 1 H, H1Ј), 5.00 (t, J = 9.5, 1 H, H4Ј), 4.38 (m, 1 H, H2),
4.34 (m, 1 H, H3), 4.12 (dd, J = 12.2 and 6.0 Hz, 1 H, H6aЈ), 4.07
(dd, J = 12.2 and 3.0 Hz, 1 H, H6bЈ), 3.83 (ddd, 1 H, J = 9.5, 6.0
and 3.0 Hz, 1 H, H5Ј), 3.73 (m, 1 H, OH), 3.71 (c, J = 8.5 Hz, 1 H,
H2Ј), 2.02, 1.99, 1.88 (3s, 9 H, 3CH3CO) ppm. 13C NMR (CDCl3,
125 MHz): δ = 170.7, 170.4, 169.5 (3CO, Ac), 166.2, 165.7, 165.3,
164.9 (4CO, Bz), 162.6 (NHCOCCl3), 134.14, 134.07, 133.5, 133.4
(4C, Bz), 130.3–128.5 (4CHpara, Bz), 99.5 (C1Ј), 80.0 (C3), 72.5
(C5Ј), 71.5 (C4), 70.88, 70.84 (C2, C3Ј), 69.9 (C6), 69.0 (C5), 68.54,
68.50 (C1, C4Ј), 62.0 (C6Ј), 57.1 (C2Ј), 20.7, 20.6, 20.5 (CH3CO)
ppm. FAB HRMS calculated for [C48H44NO18Cl3+Na]+:
1050.1516, found: 1050.1499; calculated for [C48H44NO18Cl3 +K]+:
1066.1256, found: 1066.1246.
3,4,6-Tri-O-acetyl-2-deoxy-2-trichloroacetamido-
β(1Ǟ2)-1,4,5,6-tetra-O-benzoyl- -chiro-inositol (21) and 3,4,6-Tri-
O-acetyl-2-deoxy-2-trichloroacetamido- -glucopyranosyl-β(1Ǟ3)-
1,4,5,6-tetra-O-benzoyl- -chiro-inositol (22): These pseudodisac-
D-glucopyranosyl-
D
D
D
charides were prepared from 3,4,6-tri-O-benzyl-2-deoxy-2-trichlo-
roacetamido--glucopyranosyl trichloroacetimidate (20) (160 mg,
0.269 mmol) and 1,4,5,6-tetra-O-benzoyl--chiro-inositol (1D)
(134 mg, 0.225 mmol) as described for the preparation of 13 and
15 by addition of 180 µL (0.08 equiv.) of a 0.1  solution of
TMSOTf at –40 °C in dry ether (5.6 mL) and stirring the reaction
mixture for 3 h at –40 °C. The reaction was quenched with Et3N,
the solvent was evaporated and the crude residue was purified by
flash chromatography (toluene/AcOEt = 8:2) to yield a mixture of
pseudodisaccharides 21 β(1–2) and 22 β(1–3) (5:1, 220 mg, 95%)
as a white solid.
Data for the Mixture of Pseudodisaccharides 21/22: 21 β(1–2)/
1
22 β(1–3) = I/II = 5:1, TLC, toluene/AcOEt = 7:3, Rf = 0.28. H
NMR (CDCl3, 500 MHz): δ = 8.17 (d, J = 7.5 Hz, 0.4 H, Hortho,
II), 8.14 (d, J = 7.5 Hz, 2 H, Hortho, I), 8.10 (d, J = 7.5 Hz, 2 H,
Hortho, I), 8.03 (d, J = 7.5 Hz, 0.4 H, Hortho, II), 8.02 (d, J =
8.0 Hz, 0.4 H, Hortho, II), 7.98 (d, J = 7.5 Hz, 2 H, Hortho, I),
7.83 (d, J = 7.0 Hz, 0.4 H, Hortho, II), 7.75 (d, J = 7.5 Hz, 2 H,
Hortho, I), 7.66–7.20 (m, 14.4 H, 12 H, I and 2.4 H, II, Bz), 7.18
(d, J = 8.5 Hz, 0.2 H, NHCOCCl3, II), 7.03 (d, J = 8.5 Hz, 1 H,
NHCOCCl3, II), 6.004 (t, J = 3.5 Hz, 1 H, H6, I), 5.997 (t, J =
9.5 Hz, 0.2 H, H4, II), 5.93 (t, J = 10.0 Hz, 1 H, H4, I), 5.92 (m,
0.2 H, H6, II), 5.87 (dd, J = 10.5 and 3.0 Hz, 0.2 H, H5, II), 5.79
(t, J = 3.5 Hz, 1 H, H1, I), 5.76 (dd, J = 10.5 and 3.5 Hz, 1 H, H5,
I), 5.75 (m, 0.2 H, H1, II), 5.23 (t, J = 9.5 Hz, 1 H, H3Ј, I), 5.17 (t,
J = 10.0 Hz, 0.2 H, H3Ј, II), 5.09 (d, J = 8.0 Hz, 1 H, H1Ј, I), 5.03
(t, J = 9.5 Hz, 1 H, H4Ј, I), 5.00 (d, J = 8.5 Hz, 0.2 H, H1Ј, II),
4.97 (t, J = 9.5 Hz, 0.2 H, H4Ј, II), 4.49 (td, J = 9.5 and 3.5 Hz, 1
H, H3, I), 4.47 (dt, J = 9.5 and 3.5 Hz, 0.2 H, H2, II), 4.35 (dd, J
= 9.5 and 3.5 Hz, 1 H, H2, I), 4.24 (t, J = 9.5 Hz, 0.2 H, H3, II),
4.11 (dd, J = 12.0 and 4.5 Hz, 1 H, H6aЈ, I), 4.01 (dd, J = 12.0 and
1,4,5,6-Tetra-O-benzoyl-2,3-O-(2Ј,3Ј-dimethoxybutane-2Ј,3Ј-diyl)-
chiro-inositol (25 ): A suspension of 1,4,5,6-tetra-O-benzoyl--
chiro-inositol (1 ) (0.7 g, 1.17 mmol), 2,3-butanedione (0.154 mL,
D-
D
D
1.76 mmol) and trimethyl orthoformate (0.512 mL, 4.68 mmol) in
dry MeOH (13 mL) was treated with CSA (0.032 g, 0.138 mmol).
The resulting mixture was refluxed in an argon atmosphere for 5 h,
whereupon it was cooled, neutralised with Et3N and concentrated
under vacuum. The crude product was purified by flash chromatog-
raphy (hexane/EtOAc = 8:1) to give 0.76 g of 3 (92%).
2.0 Hz, 1 H, H6bЈ, I), 4.00 (m, 0.2 H, H2Ј, II), 3.99 (dt, J = 10.5 Data of 25
D
: [α]2D0 = –6.2 (c = 0.8, CHCl3). H NMR (500 MHz,
1
and 8.5 Hz, 1 H, H2Ј, I), 3.91 (dd, J = 12.5 and 4.5 Hz, 0.2 H, H6aЈ
II), 3.70 (ddd, J = 9.5, 4.5 and 2.0 Hz, 1 H, H5Ј, I), 3.65 (dd, J =
,
CDCl3): δ = 8.14 (d, J = 8.0 Hz, 2 H, Hortho), 8.05 (m, J = 8.0 Hz,
2 H, Hortho), 7.99 (d, J = 8.0 Hz, 2 H, Hortho), 7.77 (d, J = 8.0 Hz,
12.5 and 2.0 Hz, 0.2 H, H6bЈ, II), 3.53 (m, 0.2 H, H5Ј, II), 3.21 (d, 2 H, Hortho), 7.65–7.20 (m, 12 H, 4Bz), 6.06 (t, J = 10.1 Hz, 1 H,
J = 3.5 Hz, 0.2 H, OH, II), 3.13 (d, J = 3.5 Hz, 1 H, OH, II), 1.98
H4), 5.92 (t, J = 3.6 Hz, 1 H, H6), 5.75 (dd, J = 10.1 and 3.5 Hz,
(s, 6.6 H, 2CH3CO, II + CH3CO, II), 1.94 (s, 0.6 H, CH3CO, II), 1 H, H5), 5.68 (t, J = 3.6 Hz, 1 H, H1), 4.52 (t, J = 10.2 Hz, 1 H,
1.89 (s, 0.6 H, CH3CO, II), 1.89 (s, 3 H, CH3CO, II) ppm. 13C H3), 4.36 (dd, J = 10.1 and 3.6 Hz, 1 H, H2), 3.28–3.25 (2s, 6 H,
NMR (CDCl3, 125 MHz): δ = 171.0, 170.6, 169.1 (CH3CO, II), 2OCH3), 1.27 (s, 3 H, CH3) and 1.22 (s, 3 H, CH3) ppm. 13C NMR
166.6, 165.3, 164.9, 164.5 (CO, II, Bz), 162.3 (NHCOCCl3, II), (125 MHz, CDCl3): δ = 165.8, 165.7, 165.5, 165.1 (4CO), 134.0,
133.8, 133.5, 133.4, 133.2 (CHpara Bz), 130.1, 129.9, 129.8 (CHor-
133.7, 133.5, 133.4 (4CHpara), 130.4–128.6 (16CH, Bz), 130.0,
tho, II, Bz), 129.7 (C, II, Bz), 129.6 (CHortho, II, Bz), 129.3, 129.0, 129.9, 129.3, 129.2 (4C, Bz), 100.4, 99.7 (2C, BDA), 71.3 (C5), 70.2
128.9 (C, II, Bz), 128.8, 128.6, 128.4, 128.3 (CHmeta, II, Bz), 101.3
(C4), 69.5 (C1), 69.2 (C6), 67.3 (C3), 67.0 (C2), 48.5, 48.1
(C1Ј, II), 101.2 (C1Ј, I), 92.2 (NHCOCCl3, II), 80.4 (C3, II), 78.5 (2OCH3) and 17.9, 17.7 (2CH3) ppm. FAB HRMS calcd. for
(C2, I), 72.43 (C4, I), 73.38 (C3Ј, II), 70.07 (C5Ј, I), 71.97 (C3, I + [C40H38O12+Na]+: 733.2256, found: 733.2260.
C5Ј, II), 71.69 (C3Ј, I), 71.61 (C2, II), 71.34 (C1, II), 70.03 (C5, II),
2,3-O-(2Ј,3Ј-Dimethoxybutane-2Ј,3Ј-diyl)-
solution of 1,4,5,6-tetra-O-benzoyl-2,3-O-(2Ј,3Ј-dimethoxybutane-
2Ј,3Ј-diyl)--chiro-inositol (25 ) (0.76 g, 1.07 mmol) in 9 mL of
D-chiro-inositol (26D): A
69.96 (C4, II), 69.8 (C1, I), 69.6 (C5, I), 68.7 (C6, I, II), 68.6 (C6,
I), 67.9 (C4Ј, II), 67.74 (C4Ј, I), 61.72 (C6Ј, II), 61.6 (C6Ј, I), 56.3
(C2Ј, I), 56.1 (C2Ј, II), 20.5, 20.4, 20.3 (CH3CO, II) ppm. FAB
HRMS calcd. for [C48H44NO18Cl3+H]+: 1028.1702, found:
1028.1652.
D
MeOH/THF (8:1) was treated in an argon atmosphere with 2 mL
of a 1.0  solution of MeONa/MeOH. After stirring the reaction
mixture for 2 h at room temperature, the reaction was stopped with
IR-120 and acidified to pH = 7, filtered and concentrated to give
3,4,6-Tri-O-acetyl-2-deoxy-2-trichloroacetamido-
D
-glucopyranosyl-
β(1Ǟ3)-1,4,5,6-tetra-O-benzoyl-D-chiro-inositol (23): This pseudo-
0.31 g of 26D (quantitative).
Eur. J. Org. Chem. 2006, 3947–3959
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3955

M. B. Cid, M. Martín-Lomas et al.
FULL PAPER
1
Data of 26
D
: [α]2D0 = –51.0 (c = 0.2, CHCl3), H NMR (500 MHz,
anosyl-β(1Ǟ2)-1,4,5,6-tetra-O-benzyl-
azido-3,4,6-tri-O-benzyl-2-deoxy- -glucopyranosyl-β(1Ǟ3)-1,4,5,6-
tetra-O-benzyl- -chiro-inositol (31): These pseudodisaccharides
D-chiro-inositol (29) and 2-
MeOD): δ = 3.88 (t, J = 3.2 Hz, 1 H, H1), 3.86 (t, J = 3.2 Hz, 1
D
H, H6), 3.83 (dd, J = 10.0 and 3.0 Hz, 1 H, H5), 3.77 (t, J = 8.9 Hz,
D
1 H, H4), 3.66 (dd, J = 9.0 and 3.1 Hz, 1 H, H2), 3.63 (t, J = were prepared from 3,4,6-tri-O-benzyl-2-deoxy-α--glucopyranosyl
8.9 Hz, 1 H, H3), 3.25 (s, 3 H, OCH3), 3.20 (s, 3 H, OCH3) and trichloroacetimidate (2) (68 mg, 0.11 mmol) and 1,4,5,6-tetra-O-
1.27 (2s, 6 H, 2CH3) ppm. 13C NMR (125 MHz, MeOD): δ =
benzyl--chiro-inositol (24
D) (60 mg, 0.11 mmol) as described for
101.8, 101.2 (2C, BDA), 74.5 (CH), 73.7 (CH), 73.1 (CH), 72.9
the preparation of 13 and 15 by addition of 0.08 equiv. (88 µL of
(CH), 71.1 (CH), 69.9 (CH), 49.0, 48.9 (2OCH3) and 18.8 (2CH3) a 0.1  solution) of TMSOTf at –40 °C in dry ether (2.5 mL) and
ppm. FAB HRMS calcd. for [C12H22O8+Na]+: 317.1212, found:
317.1212.
stirring the reaction mixture for 1 h at –40 °C; yield, after flash
chromatography (toluene/acetone = 30:1), 40 mg of a mixture (2:1)
of pseudodisaccharides 28 and 30 (36%), 18 mg of pseudodisaccha-
ride 29 (16%) and 14 mg of pseudodisaccharide 31 (13%). In order
to confirm the regiochemistry of these pseudodisaccharides some
of them were treated with Ac2O/Py.
1,4,5,6-Tetra-O-benzyl-2,3-O-(2Ј,3Ј-dimethoxybutane-2Ј,3Ј-diyl)-
chiro-inositol (27 ): 2,3-O-(2Ј,3Ј-dimethoxybutane-2Ј,3Ј-diyl)--
chiro-inositol (26 ) (0.31 g, 1.06 mmol) and tetrabutylammonium
D-
D
D
iodide (39 mg, 0.106 mmol) in DMF (30 mL) at –20 °C were added
to a suspension of sodium hydride (60 % in mineral oil, 0.34 g,
8.51 mmol). The resulting mixture was stirred at 0 °C for 30 min
and BnBr (1.01 mL, 8.51 mmol) was added dropwise. After stirring
the mixture for 12 h at room temperature, the reaction was com-
plete and methanol was added to the mixture. The solvent was
evaporated, the residue diluted with CH2Cl2 and washed with a
saturated solution of ammonium chloride and brine. The organic
layer was dried with Na2SO4, filtered and concentrated. The resi-
due was purified by column chromatography (hexane/Et2O = 4:1)
to give 630 mg of 5 (91%). [α]2D0 = –82.5 (c = 1.0, CHCl3). 1H NMR
(500 MHz, CDCl3): δ = 7.40–7.20 (m, 20 H, 4Ph), 4.95–4.36 (4 AB
systems, 8 H, 4CH2Ph), 4.11 (t, J = 9.8 Hz, 1 H, H3), 4.02 (dd, J
= 10.1 and 2.6 Hz, 1 H, H2), 3.93 (t, J = 9.7 Hz, 1 H, H4), 3.77
(dd, J = 9.5 and 3.4 Hz, 1 H, H5), 3.69 (t, J = 3.5 Hz, 1 H, H6),
3.67 (t, J = 2.6 Hz, 1 H, H1), 3.3 (s, 3 H, OCH3), 3.24 (s, 3 H,
OCH3), 1.36 (s, 3 H, CH3) and 1.32 (s, 3 H, CH3) ppm. 13C NMR
(125 MHz, CDCl3): δ = 139.8 (C), 139.3 (C), 139.3 (C), 138.9 (C),
128.8–127.6 (20CH, Bn), 99.9 (C, BDA), 99.2 (C, BDA), 80.5 (C5),
80.2 (C4), 76.8 (C6), 76.1 (C1), 76.0 (CH2Ph), 73.9 (CH2Ph), 73.8
(CH2Ph), 73.7 (CH2Ph), 70.5 (C3), 68.9 (C2), 48.1 (OCH3), 48.0
(OCH3), 18.3 (CH3) and 18.1 (CH3) ppm. FAB HRMS calcd. for
[C40H46O8+Na]+: 677.3102, found: 677.3090.
Data of the α(1Ǟ2) Pseudodisaccharide 28: 1H NMR (500 MHz,
C6D6): δ = 7.50–7.10 (m, 35 H, 7Ph), 5.11–4.17 (7 AB systems, 14
H, 7CH2Ph), 4.85 (d, J = 3.7 Hz, 1 H, H1Ј), 4.55 (m, 1 H, H5Ј),
4.40 (m, 1 H, H3), 4.27 (dd, J = 8.4 and 3.7 Hz, 1 H, H2), 4.20 (m,
2 H, H3Ј and H4), 4.18 (dd, J = 9.7 and 2.6 Hz, 1 H, H5), 4.01 (t,
J = 3.8 Hz, 1 H, H1), 3.89 (m, 1 H, H6), 3.77 (m, 1 H, H4Ј), 3.73
(dd, J = 10.8 and 4.4 Hz, 1 H, H6aЈ), 3.67 (dd, J = 10.4 and 1.6 Hz,
1 H, H6bЈ), 3.33 (d, J = 8.4 Hz, 1 H, OH) and 3.25 (dd, J = 10.2
and 3.7 Hz, 1 H, H2Ј) ppm. 13C NMR (125 MHz, C6D6): δ = 140.7,
139.9, 139.7, 139.6, 139.5, 139.4, 139.3 (7C), 129.2–127.9 (35CH,
Ph), 98.3 (C1Ј), 81.5 (CH), 81.2 (CH), 80.5 (CH), 79.7 (CH), 77.2
(CH), 76.5 (CH), 75.9 (CH2Ph), 75.8 (CH2Ph), 75.5 (CH2Ph), 75.1
(CH), 74.7 (CH2Ph), 74.4 (CH2Ph), 74.2 (CH), 74.1 (CH2Ph), 74.0
(CH2Ph), 72.3 (CH), 69.6 (CH2) and 64.9 (CH) ppm.
Data of the Acetylated α(1Ǟ2) Pseudodisaccharide 28: 1H NMR
(500 MHz, C6D6): δ = 6.12 (t, 1 H, J = 9.8 Hz, H3) ppm.
Data of the α(1Ǟ3) Pseudodisaccharide 30: 1H NMR (500 MHz,
C6D6): δ = 7.50–7.10 (m, 35 H, 7Ph), 5.55 (d, 1 H, J = 3.8 Hz,
H1Ј), 5.11–4.17 (7 AB systems, 14 H, 7CH2Ph), 4.93 (m, 1 H, H5Ј),
4.40 (m, 1 H, H4), 4.20 (m, 2 H, H3Ј and H3), 4.18 (dd, J = 9.7
and 2.6 Hz, 1 H, H2), 4.04 (dd, J = 9.8 and 2.6 Hz, 1 H, H5), 3.89
(m, 1 H, H1), 3.77 (m, 2 H, H6aЈ and H6), 3.63 (dd, J = 10.4 and
4.1 Hz, 1 H, H6bЈ), 3.47 (dd, J = 10.0 and 9.0 Hz, 1 H, H4Ј) and
3.10 (dd, J = 10.3 and 3.8 Hz, 1 H, H2Ј) ppm. 13C NMR (125 MHz,
C6D6): δ = 140.7, 140.6, 139.7, 139.5, 139.5, 139.4, 139.3 (7C, Ph),
129.2–127.9 (35CH, Ph), 99.7 (C1Ј), 83.1 (CH), 82.9 (CH), 82.3
(CH), 81.5 (CH), 81.2 (CH), 79.9 (CH), 79.5 (CH), 76.3 (CH2Ph),
76.1 (CH2Ph), 75.9 (CH2Ph), 75.4 (CH2Ph), 74.5 (CH2Ph), 73.9
(CH2Ph), 73.8 (CH2Ph), 71.9 (CH), 71.8 (CH), 70.3 (CH2) and 64.9
(CH) ppm.
1,4,5,6-Tetra-O-benzyl-
H2O = 9:1 (20 mL) was added to 1,4,5,6-tetra-O-benzyl-2,3-O-
(2Ј,3Ј-dimethoxybutane-2Ј,3Ј-diyl)--chiro-inositol (27 ) (0.63 g,
D-chiro-inositol (24D): A mixture of TFA/
D
0.97 mmol) and the reaction mixture was stirred at room tempera-
ture for 4 h. The solvent was evaporated and co-evaporated four
times with toluene until dry. The residue was purified by flash
chromatography (hexane/AcOEt = 4:1) to obtain 0.45 g of 27
D
(86%). [α]2D0 = –20.0 (c = 2.0, CHCl3). 1H NMR (500 MHz, C6D6):
δ = 7.40–7.20 (m, 20 H, 4Ph), 5.09–4.35 (4 AB systems, 8 H,
4CH2Ph), 4.19 (dd, J = 9.5 and 3.5 Hz, 1 H, H2), 4.09 (t, J =
9.3 Hz, 1 H, H4), 4.02 (t, J = 9.3 Hz, 1 H, H3), 3.99 (dd, J = 9.4
and 2.9 Hz, 1 H, H5), 3.89 (t, J = 3.6 Hz, 1 H, H1), 3.83 (t, J =
3.2 Hz, 1 H, H6), 2.58 (s, 1 H, OH) and 2.42 (s, 1 H, OH) ppm.
13C NMR (125 MHz, C6D6): δ = 140.5 (C), 139.8 (C), 139.6 (C),
139.5 (C), 129.2–128.1 (20CH, Ph), 82.4 (C4), 80.9 (C5), 78.4 (C1),
76.1 (C6), 76.0 (CH2Ph), 75.5 (C3), 74.4 (CH2Ph), 74.1 (CH2Ph),
73.8 (CH2Ph) and 73.0 (C2) ppm. FAB HRMS calcd. for
[C34H36O6+Na]+: 563.2407, found: 563.2409.
Data of the Acetylated α(1Ǟ3) Pseudodisaccharide 30: 1H NMR
(500 MHz, C6D6): δ = 5.79 (dd, J = 9.3 and 2.6 Hz, 1 H, H2) ppm.
Data of the β(1Ǟ2) Pseudodisaccharide 29: [α]2D0 = –11.7 (c = 0.9,
CHCl3). 1H NMR (500 MHz, C6D6): δ = 7.50–7.10 (m, 35 H, 7Ph),
5.15–4.38 (7 AB systems, 14 H, 7CH2Ph), 4.64 (d, J = 8.2 Hz, 1 H,
H1Ј), 4.55 (t, J = 9.7 Hz, 1 H, H3), 4.37 (dd, J = 9.8 and 3.4 Hz, 1
H, H2), 4.31 (t, J = 3.4 Hz, 1 H, H1), 4.24 (t, J = 9.7 Hz, 1 H, H4),
4.14 (dd, J = 9.7 and 3.7 Hz, 1 H, H5), 3.90 (t, J = 3.5 Hz, 1 H,
H6), 3.68 (t, J = 9.2 Hz, 1 H, H4Ј), 3.64 (dd, J = 10.8 and 4.2 Hz,
1 H, H6aЈ), 3.57 (dd, J = 11.0 and 1.6 Hz, 1 H, H6bЈ), 3.51 (dd, J
= 9.4 and 8.2 Hz, 1 H, H2Ј), 3.37 (t, J = 9.3 Hz, 1 H, H3Ј), 3.11
(m, 1 H, H5Ј) and 2.95 (s, 1 H, OH) ppm. 13C NMR (125 MHz,
C6D6): δ = 140.6, 140.0, 139.9, 139.7, 139.6, 139.4, 139.3 (7C),
129.2–128.1 (35CH, Ph), 104.1 (C1Ј), 83.9 (CH), 82.7 (CH), 81.9
(CH), 80.7 (CH), 78.8 (CH), 78.7 (CH), 77.0 (CH), 76.1 (CH2Ph),
75.9 (CH2Ph), 75.6 (CH), 75.4 (CH2Ph), 74.9 (CH2Ph), 74.6 (CH),
74.2 (CH2Ph), 74.0 (CH2Ph), 73.9 (CH2Ph), 69.7 (CH2) and 67.7
1,4,5,6-Tetra-O-benzyl-L-chiro-inositol (24L): This compound was
prepared from -quebrachitol, following the same experimental
procedure described for 1,4,5,6-tetra-O-benzyl--chiro-inositol
(24
2-Azido-3,4,6-tri-O-benzyl-2-deoxy-
1,4,5,6-tetra-O-benzyl- -chiro-inositol (28), 2-azido-3,4,6-tri-O-ben-
zyl-2-deoxy- -glucopyranosyl-α(1Ǟ3)-1,4,5,6-tetra-O-benzyl-
chiro-inositol (30), 2-azido-3,4,6-tri-O-benzyl-2-deoxy- -glucopyr-
D
). [α]2D0 = +20.0 (c = 2.0, CHCl3).
D
-glucopyranosyl-α(1Ǟ2)-
D
D
D-
D
3956
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 3947–3959

Simultaneous Regio- and Enantiodifferentiation in Carbohydrate Coupling
(CH) ppm. FAB HRMS calcd. for [C61H63O10N3+Na]+: 1020.4411, 79.1, 76.2, 75.2, 75.1, 75.0, 74.3, 74.2, 74.1, 73.9, 72.7, 72.0, 71.9,
FULL PAPER
found: 1020.4398.
71.5 and 71.0 (10CH and 8CH2) ppm. C61H63O10N3 (998.1872):
calcd. C 73.40 %, H 6.36 %, N 4.20 %; found: C 73.57 %, H 6.44
%, N 4.05 %.
Data of the Acetylated α(1Ǟ3) Pseudodisaccharide 34: 1H NMR
(500 MHz, C6D6): δ = 5.80 (dd, J = 9.8 and 3.1 Hz, 1 H, H2) ppm.
Data of the β(1Ǟ2) Pseudodisaccharide 33: [α]2D0 = –16.2 (c = 0.8,
CHCl3). 1H NMR (500 MHz, C6D6): δ = 7.50–7.10 (m, 35 H, 7Ph),
5.12–4.30 (7 AB systems, 14 H, CH2Ph), 4.63 (d, J = 8.2 Hz, 1 H,
H1Ј), 4.56 (m, 1 H, H3), 4.38 (dd, J = 9.9 and 2.9 Hz, 1 H, H2),
4.27–4.23 (m, 2 H, H1 and H4), 4.16 (dd, J = 10.3 and 8.2 Hz, 1
H, H2Ј), 4.13 (dd, J = 9.7 and 2.7 Hz, 1 H, H5), 3.86 (t, J = 3.5 Hz,
1 H, H6), 3.76 (s, 1 H, H4Ј), 3.75 (dd, J = 8.9 and 7.9 Hz, 1 H,
H6aЈ), 3.57 (dd, J = 8.8 and 5.7 Hz, 1 H, H6bЈ), 3.23 (m, 1 H, H5Ј),
3.16 (dd, J = 10.3 and 2.9 Hz, 1 H, H3Ј) and 3.03 (s, 1 H, OH)
ppm. 13C NMR (125 MHz, CDCl3): δ = 140.7, 140.1, 139.9, 139.7,
139.7, 139.1, 138.9 (7C), 129.3–128.1 (35CH, Ph), 104.3 (C1Ј),
82.7(CH), 81.8 (CH), 81.8 (CH), 80.7 (CH), 78.2 (CH), 77.1 (CH),
76.1 (CH2Ph), 75.7 (CH2Ph), 74.8 (CH), 74.6 (CH2Ph), 74.2
Data of the β(1Ǟ3) Pseudodisaccharide 31: [α]2D0 = –18.7 (c = 0.7,
CHCl3), 1H NMR (500 MHz, C6D6): δ = 7.65–7.10 (m, 35 H, 7Ph),
5.45–4.25 (7 AB systems, 14 H, 7CH2Ph), 4.82 (d, J = 8.2 Hz, 1 H,
H1Ј), 4.54 (m, 1 H, H2), 4.40 (t, J = 9.3 Hz, 1 H, H3), 4.29 (t, J =
9.3 Hz, 1 H, H4), 4.09 (dd, J = 9.4 and 3.7 Hz, 1 H, H5), 3.98 (t, J
= 3.7 Hz, 1 H, H1), 3.87 (t, J = 3.7 Hz, 1 H, H6), 3.74 (t, J =
9.2 Hz, 1 H, H4Ј), 3.59 (dd, J = 11.0 and 3.8 Hz, 1 H, H6aЈ), 3.53
(dd, J = 11.0 and 1.6 Hz, 1 H, H6bЈ), 3.51 (dd, J = 9.5 and 8.2 Hz,
1 H, H2Ј), 3.37 (t, J = 9.5 Hz, 1 H, H3Ј) and 3.13 (m, 1 H, H5Ј)
ppm. 13C NMR (125 MHz, C6D6): δ = 141.3, 140.0, 139.6, 139.6,
139.6, 139.5, 139.3 (7C), 129.2–127.7 (35CH, Ph), 103.2 (C1Ј), 85.5
(CH), 84.5 (CH), 81.2 (CH), 80.5 (CH), 78.9 (CH), 78.8 (CH), 76.2
(CH2Ph), 76.1 (CH), 76.0 (CH), 75.9 (CH2Ph), 75.2 (CH2Ph), 74.5
(CH2Ph), 74.3 (CH2Ph), 74.2 (CH2Ph), 74.1 (CH2Ph), 73.6 (CH),
69.5 (CH2 ) and 67.7 (CH) ppm. FAB HRMS calcd. for
[C61H63O10N3+Na]+: 1020.4411, found: 1020.4378.
2-Azido-3,4,6-tri-O-benzyl-2-deoxy-
1,4,5,6-tetra-O-benzyl-
zyl-2-deoxy- -galactopyranosyl-α(1Ǟ3)-1,4,5,6-tetra-O-benzyl-
chiro-inositol (34), 2-azido-3,4,6-tri-O-benzyl-2-deoxy- -galactopyr-
anosyl-β(1Ǟ2)-1,4,5,6-tetra-O-benzyl- -chiro-inositol (33) and 2-
azido-3,4,6-tri-O-benzyl-2-deoxy- -galactopyranosyl-β(1Ǟ3)-
1,4,5,6-tetra-O-benzyl- -chiro-inositol (35): These pseudodisaccha-
D-galactopyranosyl-α(1Ǟ2)-
D
-chiro-inositol (32), 2-azido-3,4,6-tri-O-ben- (CH2Ph), 74.1 (CH), 74.0 (CH2Ph), 73.9 (CH2Ph), 73.6 (CH), 73.0
D
D
-
(CH2Ph), 69.3 (CH2) and 64.7 (CH) ppm. FAB HRMS calcd. for
D
[C61H63O10N3+Na]+: 1020.4411, found: 1020.4409.
D
Data of the β(1Ǟ3) Pseudodisaccharide 35: [α]2D0 = –21.1 (c = 1.2,
CHCl3). 1H NMR (500 MHz, C6D6): δ = 7.63–7.10 (m, 35 H, 7Ph),
5.28–4.17 (7 AB systems, 14 H), 4.73 (d, J = 8.2 Hz, 1 H, H1Ј),
4.52 (m, 1 H, H2), 4.37 (t, J = 9.6 Hz, 1 H, H3), 4.23 (t, J = 9.7 Hz,
1 H, H4), 4.17 (dd, J = 10.2 and 8.2 Hz, 1 H, H2Ј), 4.09 (dd, J =
9.7 and 3.5 Hz, 1 H, H5), 3.99 (t, J = 3.7 Hz, 1 H, H1), 3.87 (t, J
= 3.6 Hz, 1 H, H6), 3.83(d, J = 2.6 Hz, 1 H, H4Ј), 3.72 (t, J =
8.8 Hz, 1 H, H6aЈ), 3.67 (s, 1 H, OH), 3.37 (dd, J = 8.9 and 5.3 Hz,
1 H, H6bЈ), 3.24 (m, 1 H, H5Ј) and 3.21 (dd, J = 10.3 and 2.6 Hz,
1 H, H3Ј) ppm. 13C NMR (125 MHz, C6D6): δ = 141.1, 140.1,
139.8, 139.6, 139.6, 139.3, 138.7 (7C), 129.3–127.7 (35CH, Bn),
103.7 (C1Ј), 85.6 (CH), 82.8 (CH), 80.9 (CH), 80.6 (CH), 78.7 (CH),
76.3 (CH), 76.2 (CH2Ph), 75.6 (CH2Ph), 74.5 (CH2Ph), 74.4
(CH2Ph), 74.2 (CH2Ph), 74.1 (CH2Ph), 74.0 (CH), 73.7 (CH), 73.1
(CH), 72.6 (CH2Ph), 68.9 (CH2) and 64.9 (CH) ppm. FAB HRMS
D
D
rides were prepared from 3,4,6-tri-O-benzyl-2-deoxy-α--galactop-
yranosyl trichloroacetimidate (5) (68 mg, 0.11 mmol) and 1,4,5,6-
tetra-O-benzyl--chiro-inositol (24D) (60 mg, 0.11 mmol) as de-
scribed for the preparation of 13 and 15 by addition of 0.08
equiv. (88 µL of 0.1  solution) of TMSOTf at –40 °C in dry ether
(2.5 mL) and stirring the reaction mixture for 1 h at –40 °C to yield,
after flash chromatography (hexane/AcOEt = 4:1), 13 mg of the
pseudodisaccharide 32 (12%), 7 mg of the pseudodisaccharide 34
(6%), 16 mg of the pseudodisaccharide 33 (14%) and 24 mg of the
pseudodisaccharide 35 (22%).
Data of the α(1Ǟ2) Pseudodisaccharide 32: 1H NMR (500 MHz,
C6D6): δ = 7.50–7.10 (m, 35 H, 7Ph), 5.24–4.32 (7 AB systems, 14
H, 7CH2Ph), 4.93 (d, J = 3.5 Hz, 1 H, H1Ј), 4.60 (m, 1 H, H5Ј), calcd. for [C61H63O10N3+Na]+: 1020.4411, found: 1020.4395.
4.31 (m, 1 H, H4), 4.26 (dd, J = 9.5 and 3.8 Hz, 1 H, H5), 4.20–
2-Azido-3,4,6-tri-O-benzyl-2-deoxy-D-glucopyranosyl-α(1Ǟ2)-
4.12 (m, 3 H, H2Ј, H2 and H3), 4.07 (dd, J = 11.6 and 2.5 Hz, 1 H,
H3Ј), 4.00 (br. t, J = 3.8 Hz, 1 H, H6), 3.92 (s, 1 H, H4Ј), 3.87 (br.
t, J = 3.8 Hz, 1 H, H1), 3.79 (dd, J = 8.2 and 6.4 Hz, 1 H, H6Јa) and
3.68 (dd, J = 8.2 and 6.4 Hz, 1 H, H6Јb) ppm. 13C NMR (dep135)
(125 MHz, C6D6): δ = 128.4–127.1 (35CH, Ph), 98.1 (C1Ј), 82.4
(CH), 80.9 (CH), 79.7 (CH), 77.7 (CH), 76.2 (CH), 75.9 (CH), 75.7
(CH2Ph), 74.8 (CH2Ph), 73.8 (CH2Ph), 73.7 (CH), 73.6 (CH2Ph),
73.5 (CH), 73.4 (CH2Ph), 73.3 (CH2Ph), 71.8 (CH2Ph), 70.3 (CH),
69.2 (CH2 ) and 60.7 (CH) ppm. FAB HRMS calcd. for
[C61H63O10N3+Na]+: 1020.4411, found: 1020.4420.
1,4,5,6-tetra-O-benzyl-
zyl-2-deoxy- -glucopyranosyl-α(1Ǟ3)-1,4,5,6-tetra-O-benzyl-
chiro-inositol (38), 2-Azido-3,4,6-tri-O-benzyl-2-deoxy- -glucopyr-
anosyl-β(1Ǟ2)-1,4,5,6-tetra-O-benzyl- -chiro-inositol (37) and 2-
Azido-3,4,6-tri-O-benzyl-2-deoxy- -glucopyranosyl-β(1Ǟ3)-1,4,5,6-
tetra-O-benzyl- -chiro-inositol (39): These pseudodisaccharides
L-chiro-inositol (36), 2-Azido-3,4,6-tri-O-ben-
D
L-
D
L
D
L
were prepared from 3,4,6-tri-O-benzyl-2-deoxy-α--glucopyranosyl
trichloroacetimidate (2) (63 mg, 0.101 mmol) and 1,4,5,6-tetra-O-
benzyl--chiro-inositol (24L) (55 mg, 0.101 mmol) as described for
the preparation of 13 and 15 by addition of 0.08 equiv. (80 µL of
0.1  solution) of TMSOTf at –40 °C in dry ether (2.0 mL) and
stirring the reaction mixture for 1 h at –40 °C to yield, after flash
chromatography (hexane/EtOAc = 4:1), 23 mg of a mixture (9:1)
of the pseudodisaccharides 36 and 39 (23%), 8 mg of the pseudodi-
saccharide 38 (8%) and 13 mg of the pseudodisaccharide 37 (13%).
In order to confirm the regiochemistry of these pseudodisaccha-
rides, some of them were treated with Ac2O/Py.
Data of the α(1Ǟ2) Pseudodisaccharide 36: 1H NMR (500 MHz,
C6D6): δ = 7.50–7.10 (m, 35 H, 7Ph), 5.24–4.40 (7 AB systems, 14
H, 7CH2Ph), 5.17 (d, J = 3.4 Hz, 1 H, H1Ј), 4.30–4.12 (m, 6 H,
H3Ј, H5Ј, H3, H4, H6 or H1 and H2 or H5), 4.07 (dd, J = 9.7 and
Data of the Acetylated α(1Ǟ2) Pseudodisaccharide 32: 1H NMR
(500 MHz, C6D6): δ = 6.11 (t, J = 10.1 Hz, 1 H, H3) ppm.
Data of the α(1Ǟ3) Pseudodisaccharide 34: [α]2D0 = +21.4 (c = 0.3,
CHCl3).1H NMR (500 MHz, C6D6): δ = 7.60–7.10 (m, 35 H, 7Ph),
5.78 (dd, J = 3.5 Hz, 1 H, H1Ј), 5.34–4.20 (7 AB systems, 14 H,
7CH2Ph), 5.02 (m, 1 H, H5Ј), 4.44–4.38 (m, 3 H, H2, H3, and H4),
4.12 (dd, J = 10.7 and 2.6 Hz, 1 H, H3Ј), 4.08 (dd, J = 10.8 and
3.5 Hz, 1 H, H2Ј), 3.99 (dd, J = 9.5 and 3.6 Hz, 1 H, H5), 3.92 (t,
J = 3.8 Hz, 1 H, H1), 3.81 (dd, J = 9.5 and 7.9 Hz, 1 H, H6aЈ), 3.76
(t, J = 3.7 Hz, 1 H, H6), 3.70 (s, 1 H, H4Ј), 3.54 (dd, J = 9.5 and
4.2 Hz, 1 H, H6bЈ) and 3.39 (s, 1 H, OH) ppm. 13C NMR
(125 MHz, C6D6): δ = 140.6, 139.8, 139.7, 139.6, 139.3, 139.1, 138.4 2.6 Hz, 1 H, H2 or H5), 3.91 (br. t, J = 3.5 Hz, 1 H, H1 or H6),
(7C), 129.0–128.0 (35CH, Ph), 99.9 (C1Ј), 82.6, 81.6, 80.3, 79.8, 3.70–3.63 (m, 2 H, H6aЈ, H6bЈ), 3.57 (t, J = 9.5 Hz, 1 H, H4Ј) and
Eur. J. Org. Chem. 2006, 3947–3959
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3957

M. B. Cid, M. Martín-Lomas et al.
FULL PAPER
3.12 (dd, J = 10.2 and 3.4 Hz, 1 H, H2Ј) ppm. 13C NMR (125 MHz,
C6D6): δ = 140.7, 140.1, 139.6, 139.5, 139.4, 139.3, 139.3 (7C),
129.4–128.1 (35CH, Ph), 100.7 (C1Ј), 82.7, 81.7, 81.5, 80.3, 79.6,
78.7, 76.2, 76.1, 75.9, 75.5, 75.0, 74.4, 74.3, 74.2, 73.6, 72.8, 70.2
and 65.2 (10CH and 8CH2) ppm.
dition of 0.08 equiv. (64 µL of 0.1  solution) of TMSOTf at –40 °C
in dry ether (2 mL) and stirring the reaction mixture for 1 h at
–40 °C to yield, after flash chromatography (hexane/AcOEt = 4:1),
20 mg of the pseudodisaccharides 41 (20%), 5 mg of the pseudodi-
saccharide 40 (5%) and 10 mg of the pseudodisaccharide 42 (10%).
Data of the Acetylated α(1Ǟ2) Pseudodisaccharide 36: 1H NMR
(500 MHz, C6D6): δ = 6.17 (t, J = 9.8 Hz, 1 H, H3) ppm.
Data of the α(1Ǟ2) Pseudodisaccharide 40: [α]2D0 = +30.8 (c = 0.2,
CHCl3). 1H NMR (500 MHz, C6D6): δ = 7.60–7.10 (m, 35 H, 7Ph),
5.32–4.30 (7 AB systems, 14 H, 7CH2Ph), 5.12 (d, J = 2.5 Hz, 1 H,
H1Ј), 4.28 (m, 2 H, H5Ј and H4), 4.22 (dd, J = 9.7 and 3.0 Hz, 1
H, H2), 4.20–4.13 (m, 2 H, H3 and H1), 4.08–4.02 (m, 2 H, H3Ј
and H5), 3.99 (dd, J = 10.5 and 2.5 Hz, 1 H, H2Ј), 3.92 (t, J =
3.3 Hz, 1 H, H6), 3.81 (s, 1 H, H4Ј), 3.72 (dd, J = 9.2 and 6.4 Hz,
1 H, H6aЈ) and 3.67 (dd, J = 9.2 and 6.1 Hz, 1 H, H6bЈ) ppm. 13C
NMR (125 MHz, C6D6): δ = 140.9, 140.2, 139.8, 139.7, 139.4,
139.2 and 138.9 (7C), 129.8–128.2 (35CH, Ph), 101.5 (C1Ј), 82.8,
82.7, 80.3, 79.5, 79.3, 76.3, 76.3, 75.6, 75.1, 74.8, 74.4, 74.3, 73.8,
72.8, 72.4, 71.6, 70.7 and 62.0 (10CH and 8CH2 ) ppm.
C61H63O10N3 (998.1872): calcd. C 73.40 %, H 6.36 %, N 4.20 %;
found: C 73.78 %, H 6.72 %, N 4.17 %.
Data of the α(1Ǟ3) Pseudodisaccharide 38: [α]2D0 = +25.7 (c = 0.4,
CHCl3). 1H NMR (500 MHz, C6D6): δ = 7.50–7.10 (m, 35 H, 7Ph),
5.23–4.20 (7 AB systems, 14 H, 7CH2Ph), 5.47 (d, J = 3.5 Hz, 1 H,
H1Ј), 4.30–4.17 (m, 5 H, H3Ј, H5Ј,H2, H3, and H4), 4.10 (dd, J =
9.4 and 3.6 Hz, 1 H, H5), 3.96 (br. t, J = 3.5 Hz, 1 H, H1), 3.92 (t,
J = 9.6 Hz, 1 H, H4Ј), 3.83 (t, J = 3.5 Hz, 1 H, H6), 3.53 (dd, J =
11.3 and 2.6 Hz, 1 H, H6Јa), 3.33 (d, J = 11.0 Hz, 1 H, H6Јb) and
3.20 (dd, J = 10.1 and 3.5 Hz, 1 H, H2Ј) ppm. 13C NMR (125 MHz,
C6D6): δ = 140.4, 139.9, 139.7, 139.7, 139.6, 139.5, 139.5 (7C),
129.5–128.0 (35CH, Bn), 99.8 (C1Ј), 83.1, 81.9, 81.7, 80.6, 79.5,
78.5, 76.0, 75.9, 75.8, 75.5, 74.8, 74.2, 74.1, 74.0, 73.8, 72.5, 69.3
and 65.6 (10CH and 8CH2) ppm. C61H63O10N3 (998.1872): calcd.
C 73.40 %, H 6.36 %, N 4.20 %; found: C 73.53 %, H 6.39 %, N
4.46 %.
Data of the Acetylated α(1Ǟ2) Pseudodisaccharide 40: 1H NMR
(500 MHz, C6D6): δ = 6.16 (t, J = 9.8 Hz, 1 H, H3) ppm.
Data of the Acetylated α(1Ǟ3) Pseudodisaccharide 38: 1H NMR
(500 MHz, C6D6): δ = 6.17 (dd, J = 10.2 and 3.4 Hz, 1 H, H2).
Data of the β(1Ǟ2) Pseudodisaccharide 41: [α]2D0 = +14.3 (c = 1.0,
CHCl3). 1H NMR (500 MHz, C6D6): δ = 7.65–7.10 (m, 35 H, 7Ph),
5.50–4.21 (7 AB systems, 14 H, 7CH2Ph), 4.30 (m, 1 H, H4), 4.26
(dd, J = 9.3 and 3.8 Hz, 1 H, H2), 4.20 (m, 1 H, H5), 4.16 (br. t, J
= 3.8 Hz, 1 H, H6), 4.11 (t, J = 9.3 Hz, 1 H, H3), 4.09 (m, 2 H,
H1Ј and H2Ј), 3.95 (br. t, J = 3.7 Hz, 1 H, H1), 3.66 (br. s, 1 H,
H4Ј), 3.61–3.55 (m, 2 H, H5Ј and H6Јa), 3.26 (br. t, J = 6.4 Hz, 1
H, H6Јb), 3.07 (dd, J = 9.5 and 2.5 Hz, 1 H, H3Ј) ppm. 13C NMR
(125 MHz, C6D6): δ = 141.1, 140.3, 139.8, 139.8, 139.4, 139.1 and
138.8 (7C), 129.6–127.9 (35CH, Ph), 104.1 (C1Ј), 86.3, 83.3, 81.8,
80.3, 78.9, 77.4, 76.5, 75.7, 74.9, 74.9, 74.8, 74.7, 74.6, 74.3, 73.1,
72.9, 69.5 and 64.7 (10CH and 8CH2) ppm. C61H63O10N3
(998.1872): calcd. C 73.40 %, H 6.36 %, N 4.20 %; found: C 73.45
%, H 6.21 %, N 4.36 %.
Data of the β(1Ǟ2) Pseudodisaccharide 37: [α]2D0 = +9.7 (c = 0.6,
CHCl3). 1H NMR (500 MHz, C6D6): δ = 7.56–7.10 (m, 35 H, 7Ph),
5.56–4.35 (7 AB systems, 14 H, 7CH2Ph), 4.37 (m, 2 H, H3 and
H4), 4.24 (dd, J = 9.7 and 3.7 Hz, 1 H, H2), 4.21 (dd, J = 9.6 and
2.7 Hz, 1 H, H5), 4.13 (br. t, J = 3.7 Hz, 1 H, H1), 4.07 (d, J =
7.5 Hz, 1 H, H1Ј), 3.96 (br. t, J = 3.6 Hz, 1 H, H6), 3.62–3.49 (m,
3 H, H6aЈ, H6bЈ and H4Ј), 3.32–3.25 (m, 2 H, H2Ј and H3Ј) and
3.21 (m, 1 H, H5Ј) ppm. 13C NMR (125 MHz, CDCl3): δ = 139.8,
139.1, 138.8, 138.7, 138.1, 138.0, 139.9 (7C), 128.8–127.6 (35CH,
Ph), 103.1 (C1Ј), 84.8, 83.5, 82.2, 79.3, 78.0, 77.8, 75.9, 75.9, 75.7,
75.4, 75.3, 75.2, 74.1, 73.9, 73.9, 73.8, 68.8 and 66.9 (10CH and
8CH2) ppm. C61H63O10N3 (998.1872): calcd. C 73.40 %, H 6.36 %,
N 4.20 %; found: C 73.28 %, H 6.23 %, N 4.33 %.
Data of the Acetylated β(1Ǟ2) Pseudodisaccharide 41: 1H NMR
(500 MHz, C6D6): δ = 6.12 (t, J = 10.7 Hz, 1 H, H3) ppm.
Data of the Acetylated β(1Ǟ2) Pseudodisaccharide 37: 1H NMR
(500 MHz, C6D6): δ = 6.15 (t, J = 9.9 Hz, 1 H, H3) ppm.
Data of the β(1Ǟ3) Pseudodisaccharide 42: [α]2D0 = +5.0 (c = 0.5,
CHCl3).1H NMR (500 MHz, C6D6): δ = 7.68–7.10 (m, 35 H, 7Ph),
5.22–4.25 (7 AB systems, 14 H, 7CH2Ph), 4.63 (d, J = 8.1 Hz, 1 H,
H1Ј), 4.49 (m, 1 H, H4), 4.37 (m, 1 H, H3), 4.21 (dd, J = 9.1 and
2.8 Hz, 1 H, H2), 4.15 (dd, J = 10.2 and 8.1 Hz, 1 H, H2Ј), 4.14–
4.11 (m, 2 H, H5 and H6), 3.88 (t, J = 2.9 Hz, 1 H, H1), 3.65 (d, J
= 2.6 Hz, 1 H, H4Ј), 3.63–3.57 (m, 2 H, H5Ј and H6aЈ), 3.17 (t, J =
6.5 Hz, 1 H, H6bЈ) and 3.07 (dd, J = 10.3 and 2.7 Hz, 1 H, H3Ј)
ppm. 13C NMR (125 MHz, CDCl3): δ = 139.3, 139.1, 138.8, 138.6,
138.5, 138.0 and 137.8 (7C), 128.8–127.4 (35 CH, Ph), 102.7 (C1Ј),
83.1, 81.1, 81.0, 80.5, 78.2, 75.8, 75.0, 74.8, 74.3, 73.9, 73.8, 73.8,
73.2, 72.8, 72.5, 70.6, 68.5 and 63.6 (10CH and 8CH2) ppm.
C61H63O10N3 (998.1872): calcd. C 73.40 %, H 6.36 %, N 4.20 %;
found: C 73.62 %, H 6.39 %, N 4.45 %.
Data of the β(1Ǟ3) Pseudodisaccharide 39: 1H NMR (500 MHz,
C6D6): δ = 7.70–7.10 (m, 35 H, 7Ph), 5.27–4.40 (7 AB systems, 14
H, 7CH2Ph), 4.64 (d, J = 8.1 Hz, 1 H, H1Ј), 4.35 (t, J = 9.2 Hz, 1
H, H3 or H4), 4.30–3.90 (m, 5 H, H1, H2, H3 or H4, H5 and H6),
3.68 (m, 2 H, H6aЈ, H6bЈ), 3.59 (t, J = 9.1 Hz, 1 H, H4Ј), 3.35 (dd,
J = 8.1 and 2.2 Hz, 1 H, H2Ј), 3.27 (t, J = 8.1 Hz, 1 H, H3Ј) and
3.02 (m, 1 H, H5Ј) ppm. 13C NMR (125 MHz, C6D6): δ = 140.8,
140.2, 139.6, 139.5, 139.5, 139.3, 139.2 (7C), 129.4–128.1 (35CH,
Ph), 103.2 (C1Ј), 84.4, 83.7, 83.1, 82.7, 81.9, 81.6, 81.2, 78.3, 77.8,
75.5, 75.3, 74.3, 74.2, 73.8, 73.5, 71.8, 69.2 and 67.5 (10CH and
8CH2) ppm.
Data of the Acetylated β(1Ǟ3) Pseudodisaccharide 39: 1H NMR
(500 MHz, C6D6): δ = 5.93 (dd, J = 7.1 and 1.8 Hz, 1 H, H2) ppm.
Data of the Acetilated β(1Ǟ3) Pseudodisaccharide 42: 1H NMR
(500 MHz, C6D6): δ = 5.91 (dd, J = 10.2 and 1.4 Hz, 1 H, H2)
ppm.
2-Azido-3,4,6-tri-O-benzyl-2-deoxy-
1,4,5,6-tetra-O-benzyl- -chiro-inositol (40), 2-Azido-3,4,6-tri-O-ben-
zyl-2-deoxy- -galactopyranosyl-β(1Ǟ2)-1,4,5,6-tetra-O-benzyl-
chiro-inositol (41) and 2-Azido-3,4,6-tri-O-benzyl-2-deoxy- -galac-
topyranosyl-β(1Ǟ3)-1,4,5,6-tetra-O-benzyl- -chiro-inositol (42):
D-galactopyranosyl-α(1Ǟ2)-
L
D
L-
D
Supporting Information (see also the footnote on the first page of
this article): Cartesian coordinates (Å) and Absolute Energies (a.u.)
for carbonium ions (2-N3) and (2-OMe), acceptors (1,4-diOAc) and
(1,4-diOMe) models and complexes AL3, AL2, AD3, AD2, ML3,
ML2, MD3, MD2, ALЈ3 and ALЈ2 and the spatial arrangement of
all the optimized complexes.
L
These pseudodisaccharides were prepared from 3,4,6-tri-O-benzyl-
2-deoxy-α--galactopyranosyl trichloroacetimidate (5) (50 mg,
0.08 mmol) and 1,4,5,6-tetra-O-benzyl--chiro-inositol (6
L) (43 mg,
0.08 mmol) as described for the preparation of 13 and 15 by ad-
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Eur. J. Org. Chem. 2006, 3947–3959

Simultaneous Regio- and Enantiodifferentiation in Carbohydrate Coupling
FULL PAPER
[15] One of us has recently reported experimental evidence for the
influence of the acceptor protecting groups on the regioselec-
tivity of diol glycosylation: M. B. Cid, S. Valverde, C. López,
A. M. Gómez, M. García, Synlett 2005, 1095–1100.
[16] M. B. Cid, F. Alfonso, M. Martín-Lomas, Carbohydr. Res.
2004, 339, 2303–2307.
Acknowledgments
This work was supported by the MCyT (grant BQO2002-03734).
M.B.C thanks the MCyT for a Ramón y Cajal contract. We also
thank the Centro de Computación Científica (Universidad Autó-
noma de Madrid) for computation time.
[17] Conformational analyses of donor and acceptor models were
performed using semiempirical PM3(tm) procedure, as im-
plemented in HyperChem. 6.02; see: a) J. J. P. Stewart, J. Com-
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were reoptimized by using hybrid density functional theory
(B3LYP); see: d) A. D. Becke, J. Chem. Phys. 1993, 98, 1372;
e) C. Lee, W. Yang, R. G. Parr, Phys. Rev., B 1988, 37, 785; all
of the atoms were described by means of the 6-31G(d) basis
set as implemented in Gaussian03; see: f) R. Ditchfield, W. J.
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uma, G. A. Voth, P. Salvador, J. J. Dannenberg, V. G. Zakrzew-
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vision B.03; Gaussian, Inc., Pittsburgh, PA, 2003. The same
method was used for the optimization of all the model com-
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theory/basis to characterize stationary points (all of the models
presented here were characterized as minima) and to determine
the zero-point energy (ZPE).
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[22] This torsion angle is in the range 153–167° for the rest of the
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Received: February 13, 2006
9322.
Published Online: June 28, 2006
Eur. J. Org. Chem. 2006, 3947–3959
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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