Protecting group and solvent effects in electrochemical glycosylation

Article abstract of DOI:10.1055/s-2007-986644

An investigation is undertaken into the roles of protecting groups and the solvent in the electrochemical-mediated glycosylation of manno thioglycosides. Herein notable differences are observed between electrochemical and chemical glycosylation. Georg Thi

Full text of DOI:10.1055/s-2007-986644

LETTER
2711
Protecting Group and Solvent Effects in Electrochemical Glycosylation
E
lectrochemica
u
l
Glycosylati
d
on ovic Drouin,a Richard G. Compton,b Nicole Fietkau,b Antony J. Fairbanks*a
a
Chemistry Research Laboratory, Oxford University, Mansfield Road, Oxford, OX1 3TA, UK
Fax +44(1865)275674; E-mail: antony.fairbanks@chem.ox.ac.uk
b
Physical and Theoretical Chemistry Laboratory, South Parks Road, Oxford, OX1 3QZ, UK
Received 5 July 2007
anomer (Scheme 1). However, a-mannose-containing oli-
gosaccharides are perhaps more relevant synthetic targets,
particularly as they are major components of N-glycan
oligosaccharides, and therefore attention turned to the po-
tential uses of electrochemical glycosylation for the rapid
assembly of a-oligomannose structures. Unfortunately in
this case only low levels of stereocontrol were observed;
for example whilst glycosylation10 of perbenzylated donor
thiomannoside 3a with diacetone galactose at +1.5 V in
acetonitrile did produce disaccharide 3b in good yield, a
considerable amount of the undesired b-anomer was
produced (a/b = 7:3; Scheme 1).
Abstract: An investigation is undertaken into the roles of pro-
tecting groups and the solvent in the electrochemical-mediated
glycosylation of manno thioglycosides. Herein notable differences
are observed between electrochemical and chemical glycosylation.
Key words: carbohydrates, glycosylations, electrochemistry,
solvent effects, neighbouring-group effects
The structural complexity of oligosaccharides makes
them extremely challenging synthetic targets.1 Despite
considerable synthetic efforts over the preceding decades
the synthesis of a particular oligosaccharide target still re-
mains an extremely time-consuming exercise.2 However,
recently the pioneering work of Fraser-Reid,3 Ley,4 and
Wong5 has stimulated several research groups to develop
new techniques to allow the rapid assembly of oligo-
saccharides from preformed building blocks using the
concept of reactivity tuning which allows selective
chemical activation of one glycosyl donor in the presence
of another, permitting multiple sequential glycosylations
to be performed in one pot.
OH
O
O
O
O
O
2
BnO
BnO
BnO
O
O
BnO
BnO
BnO
O
+1.8 V, MeCN,
n-Bu4NClO4
BnO
O
O
STol
O
BnO
3 Å MS, 25 °C
O
O
1b
1a
81%
Inspired by the early work on electrochemical glycosyla-
tion of Noyori,6 and Sinaÿ and Amatore,7 we became in-
trigued as to whether a similar selective type of reactivity
tuning approach would be possible for electrochemical
glycosylation. Herein we envisaged using variation of cell
potential to effect selective activation8 of one glycosyl do-
nor in the presence of a donor/acceptor which could then
itself be later activated to act as a donor at a higher poten-
tial. We subsequently undertook9 the synthesis and elec-
trochemical investigation of a variety of differentially
protected seleno-, thio- and O-glycosides as glycosyl do-
nors for use in electrochemical glycosylation reactions
and investigated their applications for the one-pot assem-
bly of oligosaccharides. However, besides the ability to
selectively activate one donor in the presence of another,
a second prerequisite for the development of efficient one-
pot oligosaccharide synthesis is that of achieving a high
level of stereocontrol during each glycosylation reaction.
In previous studies, good b-selectivity had been achieved
for electrochemical-mediated glycosylation of gluco
donors.9 For example thiotolylglucoside 1a was cleanly
glycosylated with diacetone galactose 2 in acetonitrile at
+1.8 V to give disaccharide 1b in 81% yield as the pure b-
β only
OBn
O
OBn
O
BnO
BnO
BnO
BnO
BnO
BnO
2, +1.5 V, MeCN,
n-Bu4NClO4
O
O
S
3 Å MS, 25 °C
O
3a
O
O
3b
86%
α:β = 7:3
O
OMe
Scheme 1 Contrasting stereochemical outcomes in the electroche-
mical glycosylation of perbenzylated gluco and manno thioglycosides
Perhaps the most straightforward method of achieving
high stereocontrol during a glycosylation reaction is to use
classical neighbouring-group participation of a 2-O-acyl-
protected glycosyl donor.11 However, previous reports,
particularly from Lubineau12 and co-workers, on the use
of peracetylated donors for electrochemical glycosylation
reactions indicated that such processes are low-yielding.
There were therefore two objectives of an investigation
into the use of a variety of manno thioglycoside donors
that possessed different protecting groups at the 2-posi-
tion in electrochemical glycosylation processes: first, to
try and improve the stereocontrol of glycosylation, and
second, to investigate protecting group effects on the
yield of electrochemical glycosylation (Table 1). To these
SYNLETT 2007, No. 17, pp 2711–2717
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6
.1
0
.
2
0
0
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Advanced online publication: 12.09.2007
DOI: 10.1055/s-2007-986644; Art ID: D19707ST
© Georg Thieme Verlag Stuttgart · New York

2712
L. Drouin et al.
LETTER
Table 1 Electrochemical Glycosylation of Thioglycoside Donors with Diacetone Galactose in Acetonitrile at +1.5 V
Entry
Glycosyl donor
Disaccharide
Yield
15%
Ratio a/ba
OAc
BnO
OAc
O
BnO
BnO
BnO
O
BnO
BnO
O
O
O
S
1
4:1
O
O
O
OMe
4a
4b
OPiv
O
OPiv
BnO
BnO
BnO
BnO
O
BnO
BnO
O
O
O
O
S
2
60%
9:1b
O
O
OMe
5a
5b
Me
Me
Me
Me
Me
Me
O
O
O
O
O
O
BnO
BnO
BnO
BnO
BnO
BnO
O
O
O
3
28%
7:3
S
O
O
O
OMe
6a
6b
OFmoc
O
BnO
BnO
BnO
S
4
not observed
–
–
OMe
tBu
7a
O
O
O
BnO
BnO
BnO
BnO
O
BnO
BnO
tBu
O
O
O
S
5
65%
7:3
O
O
O
OMe
8a
8b
O
O
O
BnO
BnO
BnO
BnO
BnO
BnO
O
O
N
N
O
S
6c
16%
4:1
O
O
O
O
OMe
9a
9b
a Ratios determined by 1H NMR of the crude mixture.
b Performing this electrochemical glycosylation at –20 °C did not alter the stereochemical outcome of the reaction.
c Glycosylation was carried out at +2.2 V.
Synlett 2007, No. 17, 2711–2717 © Thieme Stuttgart · New York

LETTER
Electrochemical Glycosylation
2713
ends, a series of thioglycosides 4a–9a was synthesized in participating protection and to simply increase the steric
which the 3-, 4- and 6-hydroxyls were protected as benzyl bulk of the 2-hydroxyl protecting group to try and favour
ethers, and the protection of the 2-hydroxyl was varied. formation of the desired a-disaccharide, the p-tert-butyl
Glycosylation of the 2-O-acetate-protected donor 4a with benzyl ether 8a was synthesised. Glycosylation of 8a with
diacetone galactose 2 as a model glycosyl acceptor pro- diacetone galactose under similar conditions produced
duced the desired disaccharide 4b13 in a very poor 15% disaccharide 8b17 in 65% yield, but with no improvement
yield, in line with the observations of Lubineau,12 and in in stereocontrol (a/b = 7:3) compared to the normal
contrast with the earliest report by Noyori.6 Interestingly, benzyl ether. Finally the potential use of 2-O-picolyl
the ester protection did not result in complete control of protection, which was recently reported18 as an arming
anomeric stereochemistry; (a/b = 4:1; Table 1, entry 1) participating protecting group for chemical glycosylation,
which contrasts with reports by Sinaÿ et al. on the use of was investigated. Thus picolyl-protected donor 9a was
2-O-acylated gluco donors,7c but is in line with reports synthesised and glycosylated with acceptor 2 at a slightly
from the same group on the use of a 2-O-acylated ido higher potential of +2.2 V. Disaccharide 9b was produced
donor.7d Reasoning that nucleophilic cleavage of the ester only in a poor 16% yield, although the stereochemical out-
protection may be responsible for the reduced product come (a/b = 4:1) was slightly better than for the other non-
yield glycosylation of the more robust pivaloyl-protected ester protecting groups. These results indicate that ester
donor 5a was undertaken. In line with the increased resis- protection of the 2-position is disadvantageous in terms of
tance to hydrolysis the yield of glycosylated product 5b14 yield of electrochemical glycosylation, and does not
was increased to a respectable 60% (Table 1, entry 2). invariably provide the high level of stereocontrol that is
However, once again stereocontrol, although higher than usually observed in more conventional glycosylation
for the acetate ester, was not complete (a/b = 9:1) and in reactions. The fact that the use of nonparticipating protec-
fact when this reaction was repeated at –20 °C in order to tion at the 2-position does not lead to satisfactorily high
try and improve this a selectivity, the stereochemical levels of stereocontrol exacerbates the problem. This
outcome was found to be the same (Table 1, entry 2, foot- having been said, the use of the pivaloyl group for protec-
note b).
tion of the 2-position does appear to produce acceptable
results.
Continuing the theme of steric retardation of hydrolysis
the mesitoate-protected donor 6a was synthesised. How- It was next decided to investigate more precisely why the
ever, the yield of electrochemical-mediated glycosylation low levels of glycosylation product were observed for
of 6a was considerably lower than for the pivaloate 5a, ester-protected glycosyl donors, and in particular whether
and disaccharide 6b15 was only isolated in a modest 28% this was because of ester protection specifically of the 2-
yield perhaps indicating an acid-catalysed cleavage mech- position of the donor, which could result in a potential
anism, and again with low stereocontrol (a/b = 7:3). Since hydrolysis pathway via orthoester formation. The per-
the more acid-stable Fmoc protecting group has recently benzoylated thioglycoside 10a was synthesised, and sub-
found increasingly useful application in oligosaccharide jected to electrochemical glycosylation with acceptor 2 at
synthesis,16 Fmoc-protected donor 7a was synthesised +2.2 V in acetonitrile. In this case (Table 2, entry 1) the
and glycosylated under similar conditions. However, in desired disaccharide 10b19 was produced in 49% yield as
this case, complete decomposition was observed, indicat- an anomeric mixture (a/b = 4:1). However, careful analy-
ing that Fmoc protection is not compatible with electro- sis of the reaction mixture revealed that the benzoylated
chemical glycosylation. In an attempt to move away from acceptor 11 had also been produced in 30% yield. Clearly
Table 2 Electrochemical Glycosylation of Benzoyl-Protected Donors with Diacetone Galactose
Entry
Donor
Disaccharide
Yield
Ratio a/b
Transesterification Yield
product
OBz
O
OBz
O
BzO
BzO
BzO
BzO
BzO
BzO
OBz
O
O
O
O
O
S
1
10a
10b
49%
4:1
11
30%
O
O
O
O
O
O
OMe
OBn
O
OBn
O
BzO
BzO
BzO
BzO
BzO
BzO
OBz
O
O
O
O
O
O
S
O
2
12a
12b
41%
6:1
11
30%
O
O
O
O
OMe
Synlett 2007, No. 17, 2711–2717 © Thieme Stuttgart · New York

2714
L. Drouin et al.
LETTER
this indicates that transesterification of the glycosyl Table 3 Solvent Effects in Electrochemical and One-Electron-
Oxidation-Mediated Glycosylation24 of Donors 3a and 5a
acceptor is a competing side reaction, which is no doubt
in part responsible for the lower yield of glycosylation us-
Entry Donora Activation
Methodb
Solvent Product
(yield)
Anomeric
ratio
ing ester-protected donors. In order to investigate whether
this transesterification had arisen because of the neigh-
bouring-group participation, donor 12a, which possesses
benzyl protection at the 2-position but benzoyl protection
at the 3-, 4-, and 6-hydroxyls, was synthesised. Electro-
chemical glycosylation of donor 12a was then undertaken,
to produce disaccharide 12b20 in 41% yield again as an
anomeric mixture (a/b = 6:1), and indeed benzoylated
acceptor 11 was again produced in 30% yield (Table 2,
entry 2).
1
2
3
4
5
6
7
3a
3a
3a
3a
3a
5a
5a
+2.2 V
MeCN 3b (80%)
MeCN 3b (89%)
CH2Cl2 3b (96%)
8:3
7:3
7:3
1:1
7:3
9:2
7:1
+1.9 V at –40 °C
+1.9 V
(BrC6H4)3NSbCl6 MeCN 3b (64%)
(BrC6H4)3NSbCl6 CH2Cl2 3b (49%)
+2.2 V
MeCN 5b (55%)
Two conclusions can be drawn from these experiments.
First, since the anomeric ratios of disaccharide products
are roughly equal (in fact glycosylation of the 2-O-benzyl
donor 12a is actually more a-selective), this provides
further evidence that a neighbouring-group-participation
mechanism is not operating exclusively. Second, since the
esterified acceptor 11 was isolated in the same amount in
both cases, the transesterification process does not
necessarily result via a neighbouring-group-participation/
orthoester-formation mechanism21 since this is not possi-
ble in the case of 2-O-benzyl donor 12a.
(BrC6H4)3NSbCl6 MeCN 5b (96%)
a The acceptor was in all cases diacetone galactose 2.
b All glycosylations were performed at r.t. unless otherwise stated
nificant role in determining the stereochemical outcome
of the chemical glycosylation, considerably more b-disac-
charide being formed in acetonitrile, a similar effect is not
observed for the electrochemical glycosylation. In this
case the stereochemical outcome of the reaction appears
to be largely solvent-independent. Finally both electro-
chemical and chemical glycosylation of the 2-O-pivaloyl-
protected donor 5a were undertaken in acetonitrile. Elec-
trochemical glycosylation resulted in the formation of di-
saccharide 5b in a modest 55% yield as a 9:2 a/b mixture
of anomers (Table 3, entry 6). However, chemical glyco-
sylation produced disaccharide 5b in a much improved
96% yield, as an approximate ca. 7:1 a/b mixture of
anomers (Table 3, entry 7). Taken together, these two
final results indicate that not only is chemical glycosyla-
tion of ester-protected donors more efficient than electro-
chemical glycosylation in terms of yield, but also that
higher levels of stereocontrol can be achieved chemically
since it appears that neighbouring-group participation is
not the predominant process in the latter case.
The nature of the reaction solvent is known to play a major
role in determining the stereochemical outcome of chem-
ical glycosylation reactions. In particular the use of aceto-
nitrile has been demonstrated to increase the proportion of
b-glycosides produced by the intermediacy of a-nitrilium
ions.22 In order to more definitively investigate the ste-
reochemical outcome of electrochemical glycosylation
reactions, a third series of experiments was undertaken.
Herein the any possible solvent effects were investigated
by performing glycosylations in both acetonitrile and
dichloromethane as the solvent. Moreover, a series of
oxidative chemical glycosylations of the same donor/
acceptor pairs were performed in parallel using the one-
electron oxidizing agent tris(4-bromophenyl)amminium
hexachloroantimonate [(BrC6H4)3NSbCl6]23 as the pro-
moter, and the stereochemical results of these experiments
were compared (Table 3).
In summary, it is clear that there are subtle yet important
differences between chemical and electrochemical
glycosylation reactions. One primary disadvantage of
electrochemical glycosylation processes is the poor
compatibility with ester protecting groups on the donor,
the use of which, unless hindered pivaloate esters are
employed, results in considerably reduced yields of
glycosylated product. One competing process herein is
transesterification of the glycosyl acceptor, and it is clear
that this process does not necessarily happen because of
neighbouring-group participation/orthoester formation
since esters at positions other then the 2-hydroxyl are also
transferred with equal ease. Finally neighbouring-group
participation and solvent effects, both of which are well-
established methods for achieving increased stereocontrol
of glycosylation, do not appear to affect the stereochemi-
cal outcome of electrochemical glycosylation reactions in
nearly as significant a manner as for more standard chem-
ical glycosylation processes. These observations, com-
bined with the fact that the reaction temperature also does
Glycosylation of perbenzylated thiomannoside 3a with
acceptor 2 at +2.2 V in acetonitrile gave the expected di-
saccharide 3b in 80% yield as an approximate 8:3 a/b
mixture (Table 3, entry 1). Performing the same reaction
at a slightly lower potential (+1.9 V) at low temperature
(–40 °C) did not significantly change the stereochemical
outcome of the reaction (Table 3, entry 2). Moreover,
changing the solvent to CH2Cl2 and performing the reac-
tion at this slightly lower potential gave disaccharide 3b in
an improved 96% yield, but again as a 7:3 a/b mixture
(Table 3, entry 3). However, using (BrC6H4)3NSbCl6 as a
one-electron oxidant activator in acetonitrile as solvent
gave disaccharide 3b in 64% yield as a 1:1 mixture of ano-
mers (Table 3, entry 4), whilst in contrast the use of
(BrC6H4)3NSbCl6 in CH2Cl2 gave 3b in only 49% yield as
a 7:3 mixture of anomers (Table 3, entry 5). These results
indicate that whilst the nature of the solvent plays a sig-
Synlett 2007, No. 17, 2711–2717 © Thieme Stuttgart · New York

LETTER
Electrochemical Glycosylation
2715
point the mixture was filtered through Celite®, the filtrate
was concentrated under reduced pressure, and the residue
was taken up into Et2O. Any remaining solid was removed
by filtration through Celite,® and the filtrate was again
concentrated under reduced pressure. Finally purification by
flash column chromatography (typically eluting with PE–
EtOAc, 9:1) afforded the desired disaccharide as colourless
oil.
not seem to alter the stereochemical outcome of electro-
chemical glycosylation, underline the contrasts in chemis-
try which can occur between solution-phase species and
those adsorbed on electrode surfaces.
Further investigations into the potential uses of electro-
chemical glycosylation techniques for the rapid assembly
of oligosaccharide structures are currently in progress,
and the results will be reported in due course.
(11) Wulff, G.; Röhle, G. Angew. Chem., Int. Ed. Engl. 1974, 13,
157.
(12) (a) Balavoine, G.; Gref, A.; Fischer, J.-C.; Lubineau, A.
Tetrahedron Lett. 1990, 31, 5761. (b) Balavoine, G.;
Berteina, S.; Gref, A.; Fischer, J.-C.; Lubineau, A.
J. Carbohydr. Chem. 1995, 14, 1217. (c) Balavoine, G.;
Berteina, S.; Gref, A.; Fischer, J.-C.; Lubineau, A.
J. Carbohydr. Chem. 1995, 14, 1237.
Acknowledgment
We thank the EPSRC (Project studentship GR/T24692/01 to L.D.)
for funding.
(13) Selected data for 4b (a-anomer only): [a]D22 +10 (c = 0.7,
CHCl3). 1H NMR (500 MHz, CDCl3): d = 1.33 (s, 3 H, Me),
1.34 (s, 3 H, Me), 1.43 (s, 3 H, Me), 1.52 (s, 3 H, Me), 2.15
(s, 3 H, MeCO), 3.68–3.71 (m, 2 H, H-6a, H-6b), 3.76–3.84
(m, 3 H, H-6¢a, H-6¢b, H-5a), 3.91–3.95 (m, 2 H, H-4b, H-
5b), 3.99 (dd, J2b,3b = 3.0 Hz, J3b,4b = 9.5 Hz, 1 H, H-3b), 4.22
(dd, J3a,4a = 8.0 Hz, J4a,5a = 1.5 Hz, 1 H, H-4a), 4.30 (dd,
J1a,2a = 5.0 Hz, J2a,3a = 2.5 Hz, 1 H, H-2a), 4.47 (d, J = 10.5
Hz, 1 H, CH2 of Bn), 4.49 (d, J = 12.0 Hz, 1 H, CH2 of Bn),
4.53 (d, J = 11.0 Hz, 1 H, CH2 of Bn), 4.60 (dd, J2a,3a = 2.5
Hz, J3a,4a = 8.0 Hz, 1 H, H-3a), 4.69 (d, J = 12.0 Hz, 1 H, CH2
of Bn), 4.70 (d, J = 11.0 Hz, 1 H, CH2 of Bn), 4.87 (d, J =
10.5 Hz, 1 H, CH2 of Bn), 4.90 (d, J1b,2b = 1.5 Hz, 1 H, H-
1b), 5.40 (dd, J1b,2b = 2.0 Hz, J2b,3b = 3.0 Hz, 1 H, H-2b),
5.50 (d, J1a,2a = 5.0 Hz, 1 H, H-1a), 7.10–7.36 (m, 15 H,
15 × ArH). 13C NMR (125.8 MHz, CDCl3): d = 21.1
(MeCO), 24.5 (Me), 24.9 (Me), 25.9 (Me), 26.1 (Me), 65.9
(C-4b), 66.1 (C-6), 68.6 (C-6), 68.7 (C-2b), 70.5 (C-3a),
70.6 (C-2a), 70.8 (C-4a), 71.5 (C-5a), 71.8 (CH2), 73.4
(CH2), 74.2 (C-5b), 75.1 (CH2), 78.1 (C-3b), 96.2 (C-1a),
97.9 (C-1b), 108.6 (Cqx), 109.3 (Cqy), 127.5 (ArCH), 127.6
(ArCH), 127.7 (ArCH), 127.8 (2 × ArCH), 127.9 (2 × ArCH),
128.0 (2 × ArCH), 128.3 (4 × ArCH), 128.3 (2 × ArCH),
138.0 (ArC), 138.2 (ArC), 138.4 (ArC), 170.4 (C=O).
References and Notes
(1) (a) Varki, A. Glycobiology 1993, 3, 97. (b) Dwek, R. A.
Chem. Rev. 1996, 96, 683.
(2) Davis, B. G. J. Chem. Soc., Perkin Trans. 1 2000, 2137.
(3) Mootoo, D. R.; Konradsson, P.; Udodong, U.; Fraser-Reid,
B. J. Am. Chem. Soc. 1988, 110, 5583.
(4) (a) Grice, P.; Ley, S. V.; Pietruszka, J.; Priepke, H. W. M.;
Walter, E. P. E. Synlett 1995, 781. (b) Cheung, M. K.;
Douglas, N. L.; Hinzen, B.; Ley, S. V.; Pannecoucke, X.
Synlett 1997, 257. (c) Grice, P.; Ley, S. V.; Pietruszka, J.;
Osborn, H. M. I.; Priepke, H. W. M.; Warriner, S. Chem. Eur
J. 1997, 3, 431. (d) Green, L.; Hinzen, B.; Ince, S. J.;
Langer, P.; Ley, S. V.; Warriner, S. L. Synlett 1998, 440.
(e) Douglas, N. L.; Ley, S. V.; Lücking, U.; Warriner, S. L.
J. Chem. Soc., Perkin Trans. 1 1998, 51.
(5) (a) Zhang, Z.; Ollmann, I. R.; Ye, X.-S.; Wischnat, R.;
Baasov, T.; Wong, C.-H. J. Am. Chem. Soc. 1999, 121, 734.
(b) Ye, X.-S.; Wong, C.-H. J. Org. Chem. 2000, 65, 2410.
(c) Burkhart, F.; Zhang, Z.; Wacowich-Sgarbi, S.; Wong, C.-
H. Angew. Chem. Int. Ed. 2001, 40, 1274.
(6) Noyori, R.; Kurimoto, I. J. Org. Chem. 1986, 51, 4320.
(7) (a) Amatore, C.; Jutand, A.; Mallet, J.-M.; Meyer, G.; Sinaÿ,
P. J. Chem. Soc., Chem. Commun. 1990, 718. (b)Marra,A.;
Mallet, J.-M.; Amatore, C.; Sinaÿ, P. Synlett 1990, 572.
(c) Mallet, J.-M.; Meyer, G.; Yvelin, F.; Jutand, A.;
Amatore, C.; Sinaÿ, P. Carbohydr. Res. 1993, 244, 237.
(d) Amatore, C.; Jutand, A.; Meyer, G.; Bourhis, P.;
Machetto, F.; Mallet, J.-M.; Sinaÿ, P.; Tabeur, C.; Zhang,
Y.-M. J. Appl. Electrochem. 1994, 24, 725.
(8) For a similar approach, see: (a) Yamago, S.; Kokobu, K.;
Hara, O.; Masuda, S.; Yoshida, J. J. Org. Chem. 2002, 67,
8584. (b) Yamago, S.; Kokubo, K.; Yoshida, J. Chem. Lett.
1997, 111.
(9) (a) France, R. R.; Compton, R. G.; Fairbanks, A. J.; Rees, N.
V.; Wadhawan, J. D. Org. Biomol. Chem. 2004, 2, 2188.
(b) France, R. R.; Compton, R. G.; Davis, B. G.; Fairbanks,
A. J.; Rees, N. V.; Wadhawan, J. D. Org. Biomol. Chem.
2004, 2, 2195.
(10) Typical Procedure for Electrochemical Glycosylation:
Electrochemical glycosylation was carried out using
galvanostatic system with Pt as auxiliary and working
electrodes, and Ag as the reference electrode. Under an
atmosphere of argon, glycosyl donor (ca. 70–150 mg,
1 equiv), glycosyl acceptor (ca. 30–70 mg, 1.2 equiv), n-
Bu4NClO4 (ca. 650 mg), and 3 Å MS were suspended in
anhyd MeCN (or CH2Cl2, 20 mL) and the reaction mixture
was stirred at 25 °C for 30 min prior to commencing
electrolysis. Electrolysis was then performed at the required
potential (+1.5 V to +2.2 V depending on the donor) until the
necessary charge was reached (typically 2.5 F·mol–1). At this
+
HRMS (ESI+): m/z [M + NH4 ] calcd for C41H54NO12:
752.3641; found: 752.3649.
(14) Selected data for 5b (a-anomer): [a]D20 –6 (c = 1.2 CHCl3).
IR (film): 1732 (s, C=O), 1371 (s, CO) cm–1. 1H NMR (500
MHz, CDCl3): d = 1.21 (s, 9 H, t-Bu), 1.33 (s, 3 H, Me), 1.35
(s, 3 H, Me), 1.43 (s, 3 H, Me), 1.52 (s, 3 H, Me), 3.72 (dd,
J5a,6a = 6.5 Hz, J6a,6¢a = 10.5 Hz, 1 H, H-6a), 3.72–3.74 (m, 1
H, H-6b), 3.80 (dd, J5,6¢a = 6.5 Hz, J6a,6¢a = 10.5 Hz, 1 H, H-
6¢a), 3.78–3.82 (m, 1 H, H-6¢b), 3.83–3.87 (m, 1 H, H-5b),
3.91 (app t, J3b,4b = 9.5 Hz, J4b,5b = 9.5 Hz, 1 H, H-4b), 3.95
(d app t, J4a,5a = 1.5 Hz, J5a,6a = 6.5 Hz, J5a,6¢a = 6.5 Hz, 1 H,
H-5a), 3.99 (dd, J2b,3b = 3.0 Hz, J3b,4b = 9.5 Hz, 1 H, H-3b),
4.22 (dd, J3a,4a = 8.0 Hz, J4a,5a = 1.5 Hz, 1 H, H-4a), 4.31 (dd,
J1a,2a = 5.0 Hz, J2a,3a = 2.5 Hz, 1 H, H-2a), 4.49 (d, J = 11.0
Hz, 1 H, CH2 of Bn), 4.50 (d, J = 11.0 Hz, 1 H, CH2 of Bn),
4.51 (d, J = 13.0 Hz, 1 H, CH2 of Bn), 4.60 (dd, J2a,3a = 2.5
Hz, J3a,4a = 8.0 Hz, 1 H, H-3a), 4.68 (d, J = 12.0 Hz, 1 H, CH2
of Bn), 4.69 (d, J = 11.0 Hz, 1 H, CH2 of Bn), 4.82 (d, J =
11.0 Hz, 1 H, CH2 of Bn), 4.88 (d, J1b,2b = 2.0 Hz, 1 H, H-
1b), 5.40 (dd, J1b,2b = 2.0 Hz, J2b,3b = 3.0 Hz, 1 H, H-2b), 5.51
(d, J1a,2a = 5.0 Hz, 1 H, H-1a), 7.15–7.36 (m, 15 H, 15 ×
ArH). 13C NMR (125.8 MHz, CDCl3): d = 24.5 (Me), 24.9
(Me), 25.0 (Me), 26.1 (Me), 27.1 (t-Bu), 38.9 (CqPiv), 65.8
(C-5a), 65.9 (C-6), 68.1 (C-2b), 68.8 (C-6), 70.6 (C-3a), 70.7
(C-2a), 70.8 (C-4a), 71,4 (CH2 of Bn), 71.5 (C-5b), 73.1
(CH2 of Bn), 74.1 (C-4b), 75.1 (CH2 of Bn), 78.3 (C-3b),
96.3 (C-1a), 97.8 (C-1b), 108.6 (Cq), 109.3 (Cq), 107.4
Synlett 2007, No. 17, 2711–2717 © Thieme Stuttgart · New York

2716
L. Drouin et al.
LETTER
(ArCH), 127.4 (2 × ArCH), 127.6 (ArCH), 127.9 (2 ×
ArCH), 128.1 (2 × ArCH), 128.2 (2 × ArCH), 128.2 (2 ×
ArCH), 128.3 (2 × ArCH), 138.3, 138.3, 138.4 (ArC), 138.4
(ArCH), 177.6 (C=O). HRMS (ESI+): m/z [M + Na+] calcd
for C44H56NaO12: 799.3664; found: 799.3662. Selected data
for 5b (b-anomer): [a]D20 –39 (c = 0.2, CHCl3). 1H NMR
(400 MHz, CDCl3): d = 1.24 (s, 9 H, t-Bu), 1.29 (s, 3 H, Me),
1.32 (s, 3 H, Me), 1.42 (s, 3 H, Me), 1.52 (s, 3 H, Me), 3.46
(d app t, J4,5 = 3.5 Hz, J5,6 = 3.5 Hz, J5,6¢ = 9.5 Hz, 1 H, H-
5b), 3.65 (dd, J2,3 = 3.0 Hz, J3,4 = 9.5 Hz, 1 H, H-3b), 3.69
(dd, J5,6 = 10.5 Hz, J6,6¢ = 4.0 Hz, 1 H, H-6a), 3.74–3.79 (m,
3 H, H-6b, H-6¢b, H-6¢a), 3.97 (ddd, J4,5 = 1.5 Hz, J5,6 = 10.5
(16) (a) Zhu, T.; Boons, G.-J. Tetrahedron: Asymmetry 2000, 11,
199. (b) Roussel, F.; Knerr, L.; Grathwohl, M.; Schmidt, R.
R. Org. Lett. 2000, 2, 3043.
(17) Selected data for 8b (a-anomer): [a]D20 –6 (c = 0.7, CHCl3).
IR (film): 3050 (CHAr), 2962 (CH), 1600–2000 (CHAr),
1497 (w, CH) cm–1. 1H NMR (500 MHz, CDCl3): d = 1.31
(s, 9 H, t-Bu), 1.34 (s, 2 × 3 H, 2 × Me), 1.44 (s, 3 H, Me),
1.52 (s, 3 H, Me), 3.69–3.81 (m, 5 H, H-6a, H-6¢a, H-6b, H-
6¢b, H-2b), 3.84–3.85 (m, 1 H, H-5b), 3.90 (dd, J2b,3b = 3.0
Hz, J3b,4b = 9.5 Hz, 1 H, H-3b), 3.97 (d app t, J4a,5a = 1.5 Hz,
J5a,6a = 6.5 Hz, J5a,6¢a = 6.5 Hz, 1 H, H-5a), 4.02 (app t,
J3b,4b = 9.5 Hz, J4b,5b = 9.5 Hz, 1 H, H-4b), 4.17 (dd, J3a,4a
8.0 Hz, J4a,5a = 1.5 Hz, 1 H, H-4a), 4.32 (dd, J1a,2a = 5.0 Hz,
2a,3a = 2.5 Hz, 1 H, H-2a), 4.50 (d, J = 10.5 Hz, 1 H, CH2 of
=
Hz, J5,6¢ = 4.0 Hz, 1 H, H-5a), 4.02 (dd, J3,4 = 9.5 Hz, J4,5
=
3.5 Hz, 1 H, H-4b), 4.20 (dd, J3,4 = 8.0 Hz, J4,5 = 1.5 Hz, 1 H,
H-4a), 4.28 (dd, J1,2 = 5.0 Hz, J2,3 = 2.5 Hz, 1 H, H-2a), 4.46
(d, J = 11.5 Hz, 1 H, CH2 of Bn), 4.50 (d, J = 10.5 Hz, 1 H,
CH2 of Bn), 4.55 (d, J = 12.0 Hz, 1 H, CH2 of Bn), 4.56 (dd,
J2,3 = 2.5 Hz, J3,4 = 8.0 Hz, 1 H, H-3a), 4.63 (br s, 1 H, H-1b),
4.68 (d, J = 12.0 Hz, 1 H, CH2 of Bn), 4.74 (d, J = 11.5 Hz,
1 H, CH2 of Bn), 4.83 (d, J = 11.0 Hz, 1 H, CH2 of Bn), 5.50
(d, J1,2 = 5.0 Hz, 1 H, H-1a), 5.61 (d, J2,3 = 3.0 Hz, 1 H, H-
2b), 7.10–7.40 (m, 15 H, 15 × ArH). 13C NMR (100.6 MHz,
CDCl3): d = 24.3 (Me), 25.0 (Me), 25.9 (Me), 26.0 (Me),
27.2 (t-Bu), 39.0 (CqPiv), 67.5 (C-2b), 67.8 (CH), 68.8 (C-
6), 69.0 (C-6), 70.5 (C-3a), 70.6 (C-2a), 70.9 (CH2 of Bn),
71.2 (C-4a), 73.2 (CH2 of Bn), 74.2 (CH), 75.1 (CH2 of Bn),
75.4 (CH), 80.3 (C-3b), 96.2 (C-1a), 99.3 (C-1b), 108.7
(Cq), 109.2 (Cq), 127.4 (ArCH), 127.6 (2 × ArCH), 127.6
(ArCH), 127.6 (ArCH), 128.0 (2 × ArCH), 128.1 (2 ×
ArCH), 128.2 (2 × ArCH), 128.2 (2 × ArCH), 128.3 (2 ×
ArCH), 176.6 (C=O), 137.9 (ArC), 138.5 (2 × ArC).
J
Bn), 4.54–4.58 (m, 3 H, CH2 of Bn), 4.60 (dd, J2a,3a = 2.5 Hz,
J3a,4a = 8.0 Hz, 1 H, H-3a), 4.67 (d, J = 12.5 Hz, 1 H, CH2 of
Bn), 4.69 (d, J = 12.0 Hz, 1 H, CH2 of Bn), 4.74 (d, J = 12.5
Hz, 1 H, CH2 of Bn), 4.87 (d, J = 10.5 Hz, 1 H, CH2 of Bn),
5.04 (d, J1b,2b = 1.5 Hz, 1 H, H-1b), 5.53 (d, J1a,2a = 5.0 Hz, 1
H, H-1a), 7.15–7.37 (m, 19 H, 19 × ArH). 13C NMR (100.6
MHz, CDCl3): d = 24.6 (Me), 25.1 (Me), 26.2 (Me), 26.3
(Me), 34.7 (Cq), 65.3 (C-5a), 65.5 (C-6), 69.3 (C-6), 70.8
(C-3a), 70.9 (C-2a), 71.2 (C-4a), 72.1 (CH2), 72.2 (CH2),
72.3 (C-2b), 73.5 (CH2), 74.3 (C-5b), 75.0 (C-4b), 75.3
(CH2), 80.2 (C-3b), 96.5 (C-1a), 97.3 (C-1b), 108.8 (Cq),
109.5 (Cq), 125.5 (2 × ArCH), 127.5 (2 × ArCH), 127.6
(ArCH), 127.7 (2 × ArCH), 127.8 (2 × ArCH), 127.9 (2 ×
ArCH), 128.1 (2 × ArCH), 128.3 (4 × ArCH), 128.4 (2 ×
ArCH), 135.5 (ArC), 138.6 (ArC), 138.7 (ArC), 138.8
(ArC), 150.7 (ArC). HRMS (ESI+): m/z [M + Na+] calcd for
C50H62NaO11: 861.4184; found: 861.4162. Selected data for
8b (b-anomer): [a]D20 –48 (c = 0.1, CHCl3). 1H NMR (500
MHz, CDCl3): d = 1.30 (s, 9 H, t-Bu), 1.33 (s, 3 H, Me), 1.34
(s, 3 H, Me), 1.44 (s, 3 H, Me), 1.50 (s, 3 H, Me), 3.41 (ddd,
J4b,5b = 9.5 Hz, J5b,6b = 5.0 Hz, J5b,6¢b = 2.0 Hz, 1 H, H-5b),
3.44 (dd, J2b,3b = 3.0 Hz, J3b,4b = 9.5 Hz, 1 H, H-3b), 3.62 (dd,
(15) Selected data for 6b (a-anomer only): [a]D20 –38 (c = 0.3,
CHCl3). IR (film): 3031 (CHAr), 2921 (CH), 1729 (s, C=O),
1497 (s, CH), 1072, 1260 (s, CO) cm–1. 1H NMR (500 MHz,
CDCl3): d = 1.33 (s, 3 H, Me), 1.35 (s, 3 H, Me), 1.44 (s, 3
H, Me), 1.53 (s, 3 H, Me), 2.28 (s, 2 × 3 H, 2 × Memesitoyl),
2.29 (s, 3 H, Memesitoyl), 3.69 (br d, J6b,6¢b = 10.5 Hz, 1 H, H-
6b), 3.75 (d, J5a,6a = 6.5 Hz, J6a,6¢a = 10.5 Hz, 1 H, H-6a), 3.76
(dd, J5b,6¢b = 3.0 Hz, J6b,6¢b = 10.5 Hz, 1 H, H-6¢b), 3.83 (dd,
J5a,6¢a = 6.5 Hz, J6a,6¢a = 10.5 Hz, 1 H, H-6¢a), 3.87–3.90 (m, 2
H, H-4b, H-5b), 3.98 (d app t, J4a,5a = 1.5 Hz, J5a,6a = 6.5 Hz,
J5a,6¢a = 6.5 Hz, 1 H, H-5a), 4.08–4.10 (dd, J2b,3b = 3.0 Hz,
J5a,6a = 10.5 Hz, J6a,6¢a = 9.5 Hz, 1 H, H-6a), 3.75 (dd, J5b,6b
5.0 Hz, J6b,6¢b = 10.5 Hz, 1 H, H-6b), 3.79 (dd, J5b,6¢b = 2.0 Hz,
6b,6¢b = 10.5 Hz, 1 H, H-6¢b), 3.89 (app t, J3b,4b = 9.5 Hz,
J4b,5b = 9.5 Hz, 1 H, H-4b), 4.00 (d, J2b,3b = 3.0 Hz, 1 H, H-
=
J
2b), 4.13 (br d, 1 H, H-5a), 4.22 (dd, J5a,6¢a = 2.0 Hz, J6a,6¢a
9.5 Hz, 1 H, H-6¢a), 4.23 (dd, J3a,4a = 9.0 Hz, J4a,5a = 1.5 Hz,
1 H, H-4a), 4.29 (d, J = 12.0 Hz, 1 H, CH2 of Bn), 4.34 (dd,
J1a,2a = 5.0 Hz, J2a,3a = 2.5 Hz, 1 H, H-2a), 4.40 (d, J = 12.0
Hz, 1 H, CH2 of Bn), 4.45 (s, 1 H, H-1b), 4.50 (d, J = 10.5
Hz, 1 H, CH2 of Bn), 4.56 (d, J = 12.0 Hz, 1 H, CH2 of Bn),
4.62 (dd, J2a,3a = 2.5 Hz, J3a,4a = 9.0 Hz, 1 H, H-3a), 4.63 (d,
J = 12.0 Hz, 1 H, CH2 of Bn), 4.90 (d, J = 10.5 Hz, 1 H, CH2
of Bn), 4.91 (d, J = 12.5 Hz, 1 H, CH2 of Bn), 4.98 (d, J =
12.5 Hz, 1 H, CH2 of Bn), 5.61 (d, J1a,2a = 5.0 Hz, 1 H, H-1a),
7.15–7.45 (m, 19 H, 19 × ArH). 13C NMR (125.8 MHz,
CDCl3): d = 24.4 (Me), 25.1 (Me), 26.0 (Me), 26.1 (Me),
31.4 (t-Bu), 34.5 (Cq), 68.0 (C-5a), 69.6 (C-6b), 69.9 (C-6a),
70.5 (CH), 70.8 (CH), 70.9 (CH2), 71.7 (CH), 71.9 (CH),
73.1 (CH2), 73.4 (CH2), 74.8 (C-4b), 75.1 (CH2), 75.8 (CH),
81.9 (CH), 96.4 (C-1a), 102.4 (C-1b), 108.7 (Cq), 109.5
(Cq), 125.1 (2 × ArCH), 127.4 (ArCH), 127.5 (ArCH), 127.5
(2 × ArCH), 127.6 (ArCH), 127.9 (2 × ArCH), 128.0 (2 ×
ArCH), 128.2 (4 × ArCH), 128.3 (2 × ArCH), 128.6 (2 ×
ArCH), 135.5 (ArC), 138.1 (ArC), 138.4 (2 × ArC), 150.2
(ArC). HRMS (ESI+): m/z [M + Na+] calcd for C50H62NaO11:
861.4184; found: 861.4192.
=
J3b,4b = 9.0 Hz, 1 H, H-3b), 4.25 (dd, J3a,4a = 8.0 Hz, J4a,5a
=
1.5 Hz, 1 H, H-4a), 4.31 (dd, J1a,2a = 5.0 Hz, J2a,3a = 2.5 Hz,
1 H, H-2a), 4.45 (d, J = 11.5 Hz, 1 H, CH2 of Bn), 4.47 (d,
J = 12.5 Hz, 1 H, CH2 of Bn), 4.60 (d, J = 12.0 Hz, 1 H, CH2
of Bn), 4.62 (d, J = 11.0 Hz, 1 H, CH2 of Bn), 4.63 (dd,
J2a,3a = 2.5 Hz, J3a,4a = 8.0 Hz, 1 H, H-3a), 4.81 (d, J = 11.0
Hz, 2 H, 2 × CH2 of Bn), 5.05 (d, J1b,2b = 2.0 Hz, 1 H, H-1b),
5.52 (d, J1a,2a = 5.0 Hz, 1 H, H-1a), 5.65 (dd, J1b,2b = 2.0 Hz,
J2b,3b = 3.0 Hz, 1 H, H-2b), 6.82 (s, 2 H, 2 × ArH), 7.13–7.16
(m, 2 H, 2 × ArH), 7.23–7.40 (m, 13 H, 13 × ArH). 13C NMR
(125.8 MHz, CDCl3): d = 20.0 (2 × Me), 21.1 (Me), 24.5
(Me), 24.9 (Me), 26.0 (Me), 26.2 (Me), 65.8 (C-5a), 66.0 (C-
6a), 68.8 (C-6b), 69.3 (C-2b), 70.6 (C-3a, C-2a), 70.9 (C-4a),
71.8 (C-5b), 71.9 (CH2 of Bn), 73.2 (CH2 of Bn), 74.5 (C-
4b), 75.2 (CH2 of Bn), 76.2 (C-3b), 96.3 (C-1a), 97.6 (C-1b),
108.6 (Cq), 109.4 (Cq), 127.4 (ArCH), 127.5 (ArCH), 127.6
(ArCH), 127.7 (2 × ArCH), 127.9 (2 × ArCH), 128.0 (2 ×
ArCH), 128.2 (2 × ArCH), 128.2 (2 × ArCH), 128.3 (2 ×
ArCH), 128.3 (2 × ArCH), 130.6 (Cq), 135.6 (2 × Cq), 138.1
(Cq), 138.3 (Cq), 138.3 (Cq), 139.3 (Cq), 139.3 (Cq), 169.3
(C=O). HRMS (ESI+): m/z [M + Na+] calcd for
(18) Smoot, J. T.; Pornsuriyasak, P.; Demchenko, A. V. Angew.
Chem. Int. Ed. 2005, 44, 7123.
C49H58NaO12: 861.3820; found: 861.3818. Anal. Calcd for
C49H58O12: C, 70.15; H, 6.97. Found: C, 69.76; H, 6.59.
(19) Selected data for 10b (a-anomer only): [a]D19 –61 (c = 0.3,
CHCl3). IR (film): 3010 (w, CHAr), 2988 (w, CH), 1728 (s,
C=O), 1601, 1595, 1500, 1452 (m, C=CAr), 1263, 1060 (s,
Synlett 2007, No. 17, 2711–2717 © Thieme Stuttgart · New York

LETTER
Electrochemical Glycosylation
2717
CO) cm–1. 1H NMR (500 MHz, CDCl3): d = 1.36 (s, 2 × 3 H,
2 × Me), 1.43 (s, 3 H, Me), 1.63 (s, 3 H, Me), 3.89 (dd,
5a,6a = 6.5 Hz, J6a,6¢a = 11.0 Hz, 1 H, H-6a), 3.97 (dd, J5a,6¢a
6.5 Hz, J6a,6¢a = 11.0 Hz, 1 H, H-6¢a), 4.12 (d app t, J4a,5a = 2.0
Hz, J5a,6a = 6.5 Hz, J5a,6¢a = 6.5 Hz, 1 H, H-5a), 4.34 (dd,
(C-3a), 71.1 (C-4a), 72.4 (C-3b), 73.1 (CH2 of Bn), 75.7 (C-
2b), 96.5 (C-1a), 97.9 (C-1b), 108.8 (Cq), 109.5 (Cq), 127.6,
128.4, 128.5, 129.9 (16 × ArCH), 127.7 (ArCH), 129.4
(ArC), 129.5 (ArC), 130.0 (ArC), 132.9 (ArCH), 133.3 (2 ×
ArCH), 137.8 (ArC), 165.5 (C=O), 165.9 (C=O), 166.4
J
=
+
J3a,4a = 8.0 Hz, J4a,5a = 2.0 Hz, 1 H, H-4a), 4.35 (dd, J1a,2a
5.0 Hz, J2a,3a = 2.5 Hz, 1 H, H-3a), 4.50 (dd, J5b,6b = 3.0 Hz,
6b,6¢b = 12.0 Hz, 1 H, H-6b), 4.59 (br d app t, J4b,5b = 10.0 Hz,
J5b,6b = 3.0 Hz, J5b,6¢b = 3.0 Hz, 1 H, H-5b), 4.67 (dd, J2a,3a
=
(C=O). HRMS (ESI+): m/z [M + NH4 ] calcd for
C46H52NO14: 842.3382; found: 842.3422. Selected data for
12b (b-anomer): [a]D24 –7 (c = 0.2, CHCl3). 1H NMR (500
MHz, CDCl3): d = 1.33 (s, 2 × 3 H, 2 × Me), 1.42 (s, 3 H,
Me), 1.55 (s, 3 H, Me), 3.75 (dd, J5a,6a = 6.5 Hz, J6a,6¢a = 10.5
Hz, 1 H, H-6a), 3.89 (dd, J5a,6¢a = 6.5 Hz, J6a,6¢a = 10.5 Hz, 1
H, H-6¢a), 4.00 (dd, J1b,2b = 1.5 Hz, J2b,3b = 3.5 Hz, 1 H, H-
2b), 4.02 (d app t, J4a,5a = 2.0 Hz, J5a,6a = 6.5 Hz, J5a,6¢a = 6.5
Hz, 1 H, H-5a), 4.09 (ddd, J4b,5b = 10.0 Hz, J5b,6b = 2.0 Hz,
J
=
2.0 Hz, J3a,4a = 8.0 Hz, 1 H, H-3a), 4.69 (dd, J5b,6¢b = 3.0 Hz,
J6b,6¢b = 12.0 Hz, 1 H, H-6¢b), 5.16 (d, J1b,2b = 2.0 Hz, 1 H,
H-1b), 5.57 (d, J1a,2a = 5.0 Hz, 1 H, H-1a), 5.74 (dd, J1b,2b
2.0 Hz, J2b,3b = 3.0 Hz, 1 H, H-2b), 5.91 (dd, J2b,3b = 3.0 Hz,
3b,4b = 10.0 Hz, 1 H, H-3b), 6.14 (app t, J3b,4b = 10.0 Hz,
=
J
J4b,5b = 10.0 Hz, 1 H, H-4b), 7.25–7.28 (m, 2 H, 2 × ArH),
7.33–7.45 (m, 7 H, 7 × ArH), 7.48–7.53 (m, 1 H, ArH), 7.55–
7.62 (m, 2 H, 2 × ArH), 7.84 (dd, JA,B = 8.5 Hz, JA,X = 1.5
Hz, 2 H, 2 × ArH), 7.96 (dd, JA,B = 8.5 Hz, JA,X = 1.5 Hz,
2 H, 2 × ArH), 8.06 (dd, JA,B = 8.5 Hz, JA,X = 1.5 Hz, 2 H,
2 × ArH), 8.12 (dd, JA,B = 8.5 Hz, JA,X = 1.5 Hz, 2 H,
2 × ArH). 13C NMR (125.8 MHz, CDCl3): d = 24.6 (Me),
25.1 (Me), 26.1 (Me), 26.4 (Me), 63.0 (C-6b), 66.8 (C-5a),
67.0 (C-4b), 67.7 (C-6a), 69.0 (C-5b), 70.4 (C-3b), 70.5
(C-2b), 70.8 (C-3a), 71.0, 71.1 (C-2a, C-4a), 96.5 (C-1a),
98.0 (C-1b), 108.9 (Cq), 109.6 (Cq), 128.4 (2 × ArCH),
128.5 (2 × ArCH), 128.6 (2 × ArCH), 128.7 (2 × ArCH),
129.2 (ArC), 129.3 (ArC), 129.5 (ArC), 129.8 (2 × ArCH),
129.9 (2 × ArCH), 129.9 (2 × ArCH), 130.0 (2 × ArCH),
130.1 (ArC), 133.1 (ArCH), 133.3 (ArCH), 133.5 (ArCH),
133.6 (ArCH), 165.5 (C=O), 165.5 (C=O), 165.6 (C=O),
J5b,6¢b = 4.0 Hz, 1 H, H-5b), 4.23 (dd, J3a,4a = 8.0 Hz, J4a,5a =
2.0 Hz, 1 H, H-4a), 4.25 (app t, J3b,4b = 10.0 Hz, J4b,5b = 10.0
Hz, 1 H, H-4b), 4.32 (dd, J1a,2a = 5.0 Hz, J2a,3a = 2.5 Hz, 1 H,
H-2a), 4.58 (dd, J5b,6b = 2.0 Hz, J6b,6¢b = 12.0 Hz, 1 H, H-6b),
4.62 (dd, J2a,3a = 2.5 Hz, J3a,4a = 8.0 Hz, 1 H, H-3a), 4.63 (d,
J = 12.0 Hz, 1 H, CH2 of Bn), 4.68 (d, J = 12.0 Hz, 1 H, CH2
of Bn), 4.79 (dd, J5b,6b = 4.0 Hz, J6b,6¢b = 12.0 Hz, 1 H, H-6b),
5.05 (d, J1b,2b = 1.5 Hz, 1 H, H-1b), 5.43 (dd, J2b,3b = 3.5 Hz,
J3b,4b = 10.0 Hz, 1 H, H-3b), 5.53 (d, J1a,2a = 5.0 Hz, 1 H, H-
1a), 7.16–7.31 (m, 5 H, 5 × ArH), 7.36–7.47 (m, 6 H, 6 ×
ArH), 7.53–7.61 (m, 3 H, 3 × ArH), 8.01–8.11 (m, 6 H, 6 ×
ArH). 13C NMR (125.8 MHz, CDCl3): d = 24.7 (Me), 25.1
(Me), 26.1 (Me), 26.3 (Me), 64.1 (C-6b), 66.2 (C-5a), 66.2
(C-4b), 66.4 (C-6a), 70.7 (C-2a), 70.8 (C-3a), 71.1 (C-4a),
71.6 (C-5b), 73.1 (CH2 of Bn), 74.7 (C-3b), 76.2 (C-2b),
96.5 (C-1a), 97.8 (C-1b), 108.9 (Cq), 109.5 (Cq), 127.6,
128.4, 128.5, 128.6, 130.0 (16 × ArCH), 127.8 (ArCH),
129.7 (2 × ArC), 130.0 (ArC), 133.2 (ArCH), 133.4 (2 ×
ArCH), 138.0 (ArC), 166.9 (C=O), 167.2 (2 × C=O).
(21) See for example: Ziegler, T.; Kovac, P.; Glaudemans, C. P.
J. Liebigs Ann. Chem. 1990, 613.
+
166.4 (C=O). HRMS (ESI+): m/z [M + NH4 ] calcd for
C46H50NO15: 856.3175; found: 856.3167).
(20) Selected data for 12b (a-anomer): [a]D24 –14 (c = 0.9,
CHCl3). IR (film): 3020 (w, CHAr), 2934 (w, CH), 1725 (s,
C=O), 1601, 1598, 1500, 1452 (m, C=CAr), 1270, 1069 (s,
CO), 711 (m, CH) cm–1. 1H NMR (500 MHz, CDCl3): d =
1.34 (s, 2 × 3 H, 2 × Me), 1.44 (s, 3 H, Me), 1.58 (s, 3 H, Me),
3.81 (dd, J5a,6a = 6.5 Hz, J6a,6¢a = 10.5 Hz, 1 H, H-6a), 3.94
(dd, J5a,6¢a = 6.5 Hz, J6a,6¢a = 10.5 Hz, 1 H, H-6¢a), 4.07 (d app
t, J4a,5a = 1.5 Hz, J5a,6a = 6.5 Hz, J5a,6¢a = 6.5 Hz, 1 H, H-5a),
4.13 (dd, J1b,2b = 1.5 Hz, J2b,3b = 3.0 Hz, 1 H, H-2b), 4.26 (dd,
(22) (a) Braccini, I.; Derouet, C.; Esnault, J.; Hervé du Penhoat,
C.; Mallet, J.-M.; Michon, V.; Sinaÿ, P. Carbohydr. Res.
1993, 246, 23. (b) Sinaÿ, P. Pure Appl. Chem. 1991, 63,
519. (c) Marra, A.; Esnault, J.; Veyrières, A.; Sinaÿ, P. J.
Am. Chem. Soc. 1992, 114, 6354; and references contained
therein.
J3a,4a = 8.0 Hz, J4a,5a = 1.5 Hz, 1 H, H-4a), 4.34 (dd, J1a,2a
5.0 Hz, J2a,3a = 2.5 Hz, 1 H, H-2a), 4.45 (dd, J4b,5b = 10.0 Hz,
J5b,6b = 5.0 Hz, J5b,6¢b = 2.5 Hz, 1 H, H-5b), 4.48 (dd, J5b,6b
=
(23) (a) Marra, A.; Mallet, J.-M.; Amatore, C.; Sinaÿ, P. Synlett
1990, 572. (b) Mehta, S.; Pinto, B. M. Carbohydr. Res.
1998, 310, 43.
=
5.0 Hz, J6b,6¢b = 12.0 Hz, 1 H, H-6b), 4.57 (dd, J5b,6¢b = 2.5 Hz,
J6b,6¢b = 12.0 Hz, 1 H, H-6¢b), 4.64 (dd, J2a,3a = 2.5 Hz,
J3a,4a = 8.0 Hz, 1 H, H-3a), 4.65 (d, J = 12.0 Hz, 1 H, CH2 of
(24) Typical Procedure for Chemical Glycosylation Mediated
by (4-BrC6H4)3NSbCl6: Under an atmosphere of argon,
glycosyl donor (ca. 30–90 mg, 1 equiv), glycosyl acceptor
(ca. 20–50 mg, 1.2 equiv) and 3 Å MS were suspended in
anhyd MeCN (or CH2Cl2, 10 mL) and the reaction mixture
was stirred at r.t. for 30 min prior to addition of (4-
BrC6H4)3NSbCl6 (ca. 120–340 mg, 3 equiv). After 3 h, the
mixture was filtered and the filtrate was concentrated under
reduced pressure. The residue was then purified by flash
column chromatography (typically eluting with PE–EtOAc,
9:1) to afford the desired disaccharide as a colourless oil.
Bn), 4.69 (d, J = 12.0 Hz, 1 H, CH2 of Bn), 5.11 (d, J1b,2b
=
1.5 Hz, 1 H, H-1b), 5.55 (d, J1a,2a = 5.0 Hz, 1 H, H-1a), 5.69
(dd, J2b,3b = 3.0 Hz, J3b,4b = 10.0 Hz, 1 H, H-3b), 6.06 (app t,
J3b,4b = 10.0 Hz, J4b,5b = 10.0 Hz, 1 H, H-4b), 7.15–7.38 (m,
11 H, 11 × ArH), 7.45–7.53 (m, 3 H, 3 × ArH), 7.92–8.10 (m,
6 H, 6 × ArH). 13C NMR (125.8 MHz, CDCl3): d = 24.7
(Me), 25.1 (Me), 26.1 (Me), 26.2 (Me), 63.6 (C-6b), 66.2 (C-
5a), 66.7 (C-6a), 67.4 (C-4b), 69.1 (C-5b), 70.7 (C-2a), 70.8
Synlett 2007, No. 17, 2711–2717 © Thieme Stuttgart · New York

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