Regiospecific anomerisation of acylated glycosyl azides and benzoylated disaccharides by using TiCl4

Article abstract of DOI:10.1002/chem.201302572

Chelation induced anomerisation is promoted when Lewis acids, such as TiCl₄ or SnCl₄, coordinate to the pyranose ring oxygen atom and another site, giving rise to endocyclic cleavage and isomerisation to the more stable anomer. In this research regiospecific site-directed anomerisation is demonstrated. TiCl₄ (2.5equiv) was employed to induce anomerisation of 15 glycosyl azide and disaccharide substrates of low reactivity, and high yields (>75 %) and stereoselectivies (α/β>9:1) were achieved. The examples included glucopyranuronate, galactopyranuronate and mannopyranuronate as well as N-acetylated glucopyranuronate and galactopyranuronate derivatives. A disaccharide with the α1→4 linkage found in polygalacturonan was included. The use of benzoylated saccharides was found to be important in disaccharide anomerisation as attempts to isomerise related acetyl protected and 2,3-carbonate protected derivatives were not successful. Copyright

Full text of DOI:10.1002/chem.201302572

DOI: 10.1002/chem.201302572
Regiospecific Anomerisation of Acylated Glycosyl Azides and Benzoylated
Disaccharides by Using TiCl4
Mark Farrell, Jian Zhou, and Paul V. Murphy*[a]
Abstract: Chelation induced anomeri-
sation is promoted when Lewis acids,
such as TiCl4 or SnCl4, coordinate to
the pyranose ring oxygen atom and an-
other site, giving rise to endocyclic
cleavage and isomerisation to the more
stable anomer. In this research regio-
specific site-directed anomerisation is
demonstrated. TiCl4 (2.5 equiv) was
employed to induce anomerisation of
15 glycosyl azide and disaccharide sub-
strates of low reactivity, and high yields
(>75%) and stereoselectivies (a/b>
9:1) were achieved. The examples in-
cluded glucopyranuronate, galactopyra-
nuronate and mannopyranuronate as
well as N-acetylated glucopyranuronate
and galactopyranuronate derivatives. A
disaccharide with the a1!4 linkage
found in polygalacturonan was includ-
ed. The use of benzoylated saccharides
was found to be important in disacchar-
ide anomerisation as attempts to iso-
merise related acetyl protected and
2,3-carbonate protected derivatives
were not successful.
Keywords: anomerisation · glycur-
onic acid · Lewis acids · protecting
groups · regioselectivity
Introduction
established.[5] In previous studies the presence of an azide or
a saccharide residue at the anomeric carbon led to a signifi-
cant reduction in reactivity of the linkage towards anomeri-
sation. Herein we now report the generation of a-configured
acylated glycosyl azides and benzoylated disaccharides using
TiCl4 promoted anomerisation of the corresponding b-
linked precursors. This study shows that anomerisation is in-
duced in a regiospecific manner at the glycuronic acid
anomeric carbon, providing additional evidence for the sig-
nificant rate enhancement for the Lewis acid in the presence
of the C-6 carbonyl group. In the case of the disaccharides
the use of benzoylated substrates was found to be important
in achieving anomerisation.
Glycosides are ubiquitous and important to life, health,
food, materials, energy and the environment. Despite prog-
ress, it is still viewed as being important to improve the ste-
reoselective synthesis of glycosides.[1,2] Previous studies from
our laboratory have shown that the presence of a carboxylic
acid or a derivative (e.g., ester or amide) at the C-5 of a sac-
charide, as found in glycuronic acids, leads to a significant
increase in the rate of anomerisation promoted by Lewis
acids, such as TiCl4 or SnCl4.[3] This is explained by chelation
of the pyranose ring oxygen atom and C-6 carbonyl group
to the Lewis acid facilitating endocyclic cleavage and conse-
quent glycoside bond isomerisation to the thermodynamical-
ly more stable anomer (Scheme 1). A study of factors influ-
encing anomerisation of glucose and galactose derivatives[4]
has been carried out, with the impact of protecting group
(e.g., benzoylation>acetylation) and promoter (TiCl4 >
SnCl4) on the rate and stereoselectivity of the reaction being
Results and Discussion
This study commenced with the synthesis of a variety of gly-
cosyl azide and disaccharide substrates. The methyl ester
1 was prepared as previously reported.[6] Its analogous allyl
ester 2 was generated via 1 by saponification, which was fol-
lowed by the base-mediated allylation of the carboxylic acid
and subsequent acetylation.[3] The bromide 3 was prepared
from d-galacturonic acid through acetylation,[7] subsequent
methyl ester formation and then treatment with HBr/AcOH
(Scheme 2). Treatment of this bromide with sodium azide in
DMF in an ultrasonic bath gave the azide 4.[6] The b-manno-
pyranosyl azide 6 was prepared from 5 via a glycosyl
iodide.[8] This azide 6 was then subjected to Zemplꢀn deace-
tylation followed by one pot silylation–benzoylation to give
the TBDPS derivative 7. Removal of the the silyl protecting
group, followed by oxidation and base-mediated esterifica-
tion gave 8.
Scheme 1. Lewis acid promoted anomerisation by endocyclic cleavage.
[a] M. Farrell, Dr. J. Zhou, Prof. Dr. P. V. Murphy
School of Chemistry, National University of Ireland Galway
University Road, Galway (Ireland)
E-mail: paul.v.murphy@nuigalway.ie
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.20132752.
14836
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 14836 – 14851

FULL PAPER
Scheme 3. Synthesis of b-azides 13 and 14.
tetrabutylammonium azide in CH2Cl2.[9] These azides were
then treated with sodium methoxide in methanol to bring
about O-deacetylation and this was followed by one pot sily-
lation–benzoylation to give 11 and 12.[10] The TBDPS group
was removed from 11 and 12 using HF/pyridine and the re-
sulting primary alcohol was oxidised to the carboxylic acid
using TEMPO/BAIB. Initial attempts to prepare the methyl
ester by base-mediated esterification as described for other
acids above gave low yields. However, the esterification
with p-toluenesulfonic acid in MeOH gave the desired
azides 13 and 14 in improved yields.
The preparation of the disaccharide 20 was carried out
from azide 15.[11] Deacetylation followed by treatment of
1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane (TIPDSCl2) in
the presence of pyridine gave 16 in which both 4- and 6-OH
groups are protected. The TIPDS group was then re-
AHCTUNGTREGaNNNU rranged, using p-toluenesulfonic acid in DMF, so as to pro-
tect the 3- and 4-OH groups.[12] Then oxidation of the pri-
mary alcohol to the acid using TEMPO/BAIB followed by
esterification gave 17. Glycosidation using the trichloroaceti-
midate donor 18 gave 19.[13] The TIPDS protecting group
was removed using HCl/MeOH and subsequent treatment
with benzoyl chloride and pyridine gave the disaccharide 20
(Scheme 4).
Scheme 2. Synthesis of b-azides 2, 4 and 8.
An approach similar to that used for the mannuronic acid
derivative 8 was adopted for the preparation of the 2-deoxy-
N-acetyl-glycuronides (Scheme 3). The a-glycosyl bromides
9 and 10 were converted to the corresponding b-azides using
Scheme 4. Synthesis of 20.
Chem. Eur. J. 2013, 19, 14836 – 14851
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
14837

P. V. Murphy et al.
Scheme 5. Synthesis of 27.
The synthesis of disaccharide 27 began from the allyl gly-
coside 21 (Scheme 5).[14] Deacetylation followed by treat-
ment with TBDPSCl in the presence of pyridine and subse-
quent benzoylation gave 22. Removal of the TBDPS group
followed by oxidation and esterification gave 23. The allyl
group was removed using PdCl2 to give a hemiacetal. Subse-
quent treatment of this hemiacetal with trichloroacetonitrile
in the presence of DBU gave donor 24.[15] The disilyloxy de-
rivative 25, prepared from 16 (Scheme 3), was used to give
acceptor 26 through regioselective acetylation at the 6-OH.
The glycoside bond forming reaction between 24 and 26
then gave the disaccharide 27.
Scheme 6. Synthesis of 30.
The glucosyl azide 28, prepared by deacetylation of 15,
was next regioselectively silylated using TBDPSCl. The re-
maining hydroxyl groups were benzoylated and removal of
the TBDPS group with TBAF gave acceptor 29. The glyco-
side coupling reaction of 29 with 24 gave disaccharide 30
(Scheme 6).
of the free OH groups in the aglycon of the intermediate
gave 32.
Azide 28 was used to prepare 34 and 35. Treatment of 28
with dimethoxypropane under acidic conditions led to intro-
The diol 16 was used to pre-
pare 31 and 32 (Scheme 7).
Thus, the treatment of 16 with
acetyl chloride in the presence
of collidine led to the regiose-
lective introduction of an
acetyl group at the 2-OH.[16]
Subsequent glycosidation of
this acceptor with 24 gave 31.
Removal of the disilyloxy
group using HCl/MeOH also
led to the selective removal of
the acetate from 31 but not the
benzoate protecting groups.
The subsequent benzoylation
Scheme 7. Synthesis of 32.
14838
www.chemeurj.org
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 14836 – 14851

Regiospecific Anomerisation
FULL PAPER
duction of an acetonide group at the 4- and 6-OH groups.
Then treatment with TIPDSCl2 in pyridine placed the
TIPDS protecting group onto the 2- and 3-OH groups. Re-
moval of the acetonide and regioselective acetylation gave
33. The glycoside coupling treatment of 33 with 24 gave di-
ACHTUNGTRENNUNGsaccharide 34. Concomitant removal of the TIPDS protect-
ing group and the acetate using Amberlyst-15H+ in metha-
nol followed by benzoylation of the free OH groups gave 35
(Scheme 8).
Scheme 9. Synthesis of 39.
41 with the galactose acceptor 42 gave the disaccharide 43
in good yield.[17] Then the removal of the TBDPS, followed
by oxidation, esterification, removal of the benzyl groups
and finally benzoylation gave 44 (Scheme 10).
Scheme 8. Synthesis of 35.
With a series of disaccharides based on glucuronic acid in
hand, our attention next turned to preparation of disaccha-
ACHTUNGTRENNUNGrides based on galacturonic acid. Hence, the donor 37 was
required and its preparation was commenced from d-galac-
tose which was first tritylated at the 6-OH group and then
the remaining hydroxyl groups then benzoylated. Acid cata-
lysed hydrolysis of the trityl group gave 36. Subsequent oxi-
dation of the primary alcohol and esterification followed by
glycosyl bromide formation and silver ion promoted hydro-
ACHTUNGTRENNUNGlysis of the bromide gave a hemiacetal. Treatment of the
hemiacetal with trichloroacetonitrile in the presence of
DBU gave 37. The acceptor 38 was prepared from methyl
a-d-galactopyranoside by introduction of a benzylidene at
the 4- and 6-OH groups, benzoylation of the 2- and 3-OH
groups and then removal of the benzylidene. The glycoside
coupling reaction of 37 and diol 38 was regioselective with
bond formation occurring at the primary alcohol. Subse-
quent benzoylation of the initially formed glycoside gave 6-
O-linked 39 (Scheme 9).
The 4-O-linked disaccharide 44 was prepared starting
from thioglycoside 40. Deacetylation of 40 followed by se-
lective introduction of the TBDPS group at the primary al-
cohol and subsequent benzoylation gave 41. The coupling of
Scheme 10. Synthesis of 44.
Chem. Eur. J. 2013, 19, 14836 – 14851
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
14839

P. V. Murphy et al.
The anomerisation study commenced with a range of sub-
strates in hand. This began with the azide 1 (Table 1,
entry 1), which when subjected to treatment with SnCl4
(0.5 equiv) was only partially converted (~5% conversion)
tion. The excellent stereoselectivities observed are in part
due to the use of 2.5-fold excess TiCl4. In an earlier study on
O- and S-glycosides the use of 2.5–3.0 equivalents of TiCl4
was found to be optimum in terms of maximizing the a/
b ratio. The impact of Lewis acid concentration
on stereoselectivity of the glycosyl azides is ex-
plained by coordination of the Lewis acid at
Table 1. Anomerisation of glycosyl azides.[a]
Entry
Substrate (b-anomer)
Product (a-anomer)
Reagents,
a/b ratio
(yield [%])
higher concentrations to the anomeric azide,
which influences the anomer equilibrium. It is
proposed that coordination at this site leads to
enhancement of the anomeric effect. The use of
TiCl4 at lower or higher amounts gives rise to a re-
duction in stereoselectivity. The use of TiCl4 at
higher concentration than 0.5 equiv also enhances
the rate, which is most likely important to induce
isomerisation of the less reactive substrates as is
the case with the glycosyl azides.
Having successfully achieved the anomerisation
of the glycosyl azides, we next turned our atten-
tion to disaccharide linkages. In previous research
we observed the partial anomerisation (~33%) of
an acetylated disaccharide using 0.5 equiv TiCl4
after 24 h in nitromethane. Encouraged that use
of 2.5 equivalents of TiCl4 facilitated the re-
conditions[b]
ACHTUNGTRENNUNG
1
2
3
A
B
B
5:95 (90)
95:5 (91)
94:6 (82)
1
45
4
5
6
B
B
B
>97:3 (93)
>95:5 (90)
>95:5 (90)
AHCTUNGTREGUNaNN rrangement of glycosyl azides we explored these
conditions with the series of disaccharides shown
in Table 2 (entries 1–8). Gratifyingly, these disac-
charides were all successfully isomerised to give
the 1,2-cis glycosides 52–59. The yields were >
75% and the stereoselectivity greater than 9:1. In
a number of cases the selectivity was >95:5, with
the b-configured starting disaccharide not being
detected in the product mixture by 1H NMR
spectroscopy. In the case of the reaction of 44
conversion of its methyl glycoside to the corre-
sponding glycosyl chloride occurred to a degree
7
8
B
B
9:1 (87)
>90:10 (94)
[a] Experimental and analytical data of all compounds are available in the Supporting
Information. [b] A: SnCl4 (0.5 equiv) CH2Cl2, 208C, 24 h. B: TiCl4 (2.5 equiv) CH2Cl2,
ꢀ158C, 48 h.
to the a-anomer 45 after 24 h. This observation is indicative
of a slow anomerisation reaction as reactions of simpler ace-
tylated-O-glycosides were complete under these condi-
tions.[5] However, when 1 was left to stand in the presence
of TiCl4 in 2.5-fold excess (entry 2) in a freezer at ꢀ15 to
ꢀ188C for 48 h then 45 was isolated in high yield (94%)
and with high stereoselectivity (ratio of 1/45=19:1). The use
of TiCl4 under these conditions was found to be successful
for a range of the glycosyl azides (Table 1, entries 2–8). The
yields of the products (>82%) and stereoselectivities (a/b>
9:1) were high. The glycosyl azides successfully anomerised
included glucuronic acid, galacturonic acid, mannuronic acid
and 2-deoxy-2-acetamido-d-glucuronic acid and 2-deoxy-2-
acetamido-galacturonic acid derivatives. In the latter two ex-
amples the presence of the acetamido group in 13/14 did not
impair the glycosyl azide isomerisation which gave 49/50 ste-
reospecifically (entries 6 and 7). The regiospecific anomeri-
sation of the glycosyl azide linkage in disaccharide 20 was
also achieved (entry 8), which demonstrated clearly the rate
enhancement brought about by the presence of the glucur-
onic acid carboxylate leading to the site-directed anomerisa-
(~15%), explaining the lower yield of 56. Anomerisation of
disaccharides with a variety of glycosidic linkages (1!6, 1!
4, 1!3 and 1!2) were all achieved and the successful ex-
amples included both glucuronic acid and galacturonic acid
linkages. In contrast with the azides in Table 1, the glycosyl
azide group in each disaccharide in Table 2 did not anomer-
ise. Anomerisation occurred only at the site where efficient
chelation to the C-6 carbonyl group could occur. The regio-
specific nature of the reaction is worth noting and this pro-
vides additional convincing evidence for the rate enhancing
effect of the C-6 carbonyl group. The TIPDS protecting
group (Table 2, entries 6–8) was also highly compatible with
the reaction conditions, especially when located on the agly-
con. This contrasted with attempted anomerisation of the
azides 17 and 19 (Scheme 4), which were not successful. The
TIPDS group may hinder the approach of the Lewis acid in
17/19. The diACTHUNTGRNEUNGsilyloxy group would be less likely to cause
steric hindrance at the chelation site when placed on the
aglycon.
The results described herein demonstrate a broader appli-
cation of anomerisation for acylated substrates than hereto-
14840
www.chemeurj.org
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 14836 – 14851

Regiospecific Anomerisation
FULL PAPER
Table 2. Anomerisation of disaccharides.
tion would have been fast in
these cases given that they
contain both the 2,3-trans car-
bonate and C-6 carbonyl
group, both of which promote
endocyclic cleavage. However,
the reaction of 61–65 led to in-
tractable products when sub-
jected to various Lewis acid
promoters. Anomerisation of
more reactive saccharides (e.g.,
benzyl protected saccharides)
without the 2,3-trans carba-
mate or 2,3-trans carbonate, in-
cluding that promoted by
TiCl4, have been carried out
previously and this has includ-
ed some examples of disac-
Entry
Substrate (b-anomer)
Product (a-anomer)
Reagents,
a/b ratio
(yield [%])
conditions[b]
ACHTUNGTRENNUNG
1
B
B
>90:10 (92)
2
3
95:5 (94)
B
95:5 (87)
charide
anomerisation.[19,20]
There are reports in which
anomerisation with benzylated
saccharides give high yields but
in other cases they proceed
with low yield (<50%). It is
possible that TiCl4 could cause
the removal of benzyl groups,
which would complicate the
anomerisation of benzylated
substrates. In our hands acetyl
and benzoyl groups have been
found to be stable to TiCl4. Al-
though benzoyl groups are
more electron withdrawing
than benzyl groups and acetate
groups they still confer suffi-
cient reactivity to enable the
anomerisation and they are
faster than for acetylated sub-
strates. In a previous study the
SnCl4 promoted anomerisation
of 2,3,4-tri-O-benzoylated glu-
4
5
B
B
>90:10 (92)
95:5 (94)
6
7
B
C
95:5 (90)
>95:5 (92)
8
C
>90:10 (75)
curonides
were
2–3-times
faster than corresponding tri-
O-acetylated analogues. This
contrasts with impact of ben-
zoate groups compared to ace-
tate groups on reactivity in
[b] B: TiCl4 (2.5 equiv) CH2Cl2, ꢀ158C, 48 h; C: TiCl4 (2.5 equiv), CH2Cl2, ꢀ208C, 36 h.
fore described. The presence of the benzoyl groups in the
saccharides in which anomerisation takes place is important
as the anomerisation reaction of 60 under the conditions de-
scribed were not successful. Anomerisation with weaker
Lewis acids and also SnCl4 has been reported for pyrano-
sides which have 2,3-trans carbamate or 2,3-trans carbonate
groups, which demonstrate increased susceptibility to endo-
cyclic cleavage and anomerisation due to inherent
strain.[18,19] The disaccharides 61–65 were also investigated as
part of this work as it had been anticipated that anomerisa-
other carbohydrate-based model systems.[21] It is not clear
yet why it is the case that anomerisation becomes possible
for the benzoylated disaccharides compared to acetylated
derivatives. Aside from our own investigations and that
shown herein there has been limited investigation to date on
anomerisation of acylated disaccharides.[22]
In terms of application there is potential for anomerisa-
tion of glycuronic acids and some applications have been re-
cently described, such as the synthesis of S- and O-glyco-
AHCTUNGTRENNUNG
lipids.[23] Importantly, homogalacturonan is a major pectic
Chem. Eur. J. 2013, 19, 14836 – 14851
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
14841

P. V. Murphy et al.
removed under diminished pressure. Flash chromatography of the resi-
due (petroleum ether/EtOAc 1:1) gave 4 (0.21 g, 92%) as a white solid;
[a]D =16.3 (c 0.6, CH2Cl2); 1H NMR (500 MHz, CDCl3): d=5.74 (dd, 3J-
3
(H,H)=3.5, 1.4 Hz, 1H; H-4), 5.19 (dd, J
N
3
3
5.09 (dd, J
N
H-1), 4.39 (d, 3J
AHCTUNGTRENNUNG
3H; COCH3), 2.09 (s, 3H; COCH3), 2.00 ppm (s, 3H; COCH3);
13C NMR (126 MHz, CDCl3): d=170.1 (CO2CH3), 169.8, 169.4, 165.9 (3ꢂ
COCH3), 88.6 (C-1), 74.2 (C-5), 70.5 (C-3), 68.1 (C-4), 67.8 (C-2), 53.1
(CO2CH3), 20.8, 20.7 ppm (2s) (3ꢂCOCH3); IR (film): n˜ =2980, 2119,
1771, 1737, 1273, 1239, 1210, 1051 cmꢀ1
; ESI-HRMS calcd for
C13H17O9N3Na 382.0862, found m/z (%) 382.0866 [M+Na]+.
2,3,4,6-Tetra-O-acetyl-b-d-mannopyranosyl azide (6): Penta-O-acetyl-a-
d-mannose 5 (3 g, 7.7 mmol) was dissolved in CH2Cl2 (80 mL), I2 (2.74 g,
10.8 mmol) was added followed by the slow addition of Et3SiH (1.72 mL,
10.8 mmol; warning exothermic). The reaction was heated at reflux for
20 min and was then cooled to room temperature, diluted with CH2Cl2
(80 mL) and washed with satd. aq. NaHCO3 (150 mL) containing 10%
Na2S2O3. The aqueous phase was further extracted with CH2Cl2 (50 mL)
and the combined organic extracts were dried over Na2SO4, filtered and
the solvent was removed under diminished pressure. The residual glyco-
syl iodide was taken up in CH2Cl2 (60 mL) and tetrabutylammonium
azide (3.3 g, 11.6 mmol) was added. The reaction mixture was stirred,
overnight, before being diluted with CH2Cl2 (50 mL) and extracting with
1m HCl (100 mL). The aqueous phase was further washed with CH2Cl2
(30 mL) and the combined organic extracts were dried over Na2SO4, fil-
tered and the solvent was removed under diminished pressure. Flash
chromatography of the residue (petroleum ether/EtOAc 1:1) gave 6
(2.1 g, 64%) as a white solid; [a]D =ꢀ70.6 (c 0.3, CH2Cl2); 1H NMR
polymer of a-homogalacturonan and compounds related to
59 could be envisaged as building blocks for the synthesis of
homogalacturonan fragments, which would be important for
plant scientists.[24] The conditions described herein provide
an alternative access to a-glycuronides.[25] a-Glycuronides
are components of bacterial polysaccharides and hemicellu-
loses, providing a range of interesting target molecules. Al-
though the presence of the uronate is necessary for the most
efficient anomerisations,[26] it is possible to subsequently
chemically transform the carboxylic acid group of the uro-
nate (e.g., reduction) to increase the diversity of products
that can be obtained. The azide group is the precursor to tri-
azole-based conjugates prepared by metal catalysed alkyne–
azide cycloaddition reactions.[27] Glycosyl triazoles have
been prepared from the corresponding azide and a-glycosyl
azides have also been used for the synthesis of a-glycosyl
amides.[11b,28,29] The number of a-glycosyl azides is limited in
the literature and, until now, these have usually been pre-
pared by nucleophilic substitution of the b-glycosyl halide.[30]
In summary, we have described chelation-induced anom-
erisation of acylated glycosyl azides and disaccharide sub-
strates. The work has included regiospecific or site-directed
anomerisation. Further exploration of this reaction, in terms
of understanding how the rates can be enhanced, including
improving the activity of the promoter is under way. There
are intriguing possibilities if regioselective or site-directed
anomerisation of higher-order oligosaccharides or polysac-
charides can ultimately be achieved. Understanding factors
that influence rates of anomerisation will help chemists to
achieve isomerisation of glycosidic linkages in increasingly
complex substrates.
(500 MHz, CDCl3): d=5.44 (dd, 3J
(aptt, 3J(H,H)=10.0 Hz, 1H; H-4), 5.04 (dd, 3J
H-3), 4.73 (d, J
(H,H)=5.7 Hz, 1H; H-6a), 4.20 (dd, 2J
2.5 Hz, 1H; H-6b), 3.76 (ddd, 3J
(H,H)=10.0, 5.7, 2.5 Hz, 1H; H-5), 2.20
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
3
2
3
N
ACHTUNGTRENNUNG
A
R
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
(s, 3H; COCH3), 2.11 (s, 3H; COCH3), 2.05 (s, 3H; COCH3), 1.99 ppm
(s, 3H; COCH3); 13C NMR (126 MHz, CDCl3): d=170.6, 169.9 (2s),
169.5 (each COCH3), 85.1 (C-1), 74.6 (C-5), 70.9 (C-3), 69.2 (C-2), 65.3
(C-4), 62.3 (C-6), 20.7, 20.6, 20.5 ppm (each COCH3); IR (film): n˜ =2115,
1744, 1366, 1238, 1209, 1038 cmꢀ1
; ESI-HRMS calcd for C6H15N4O5
391.1465, found m/z (%) 391.1469 [M+NH4]+.
6-O-tert-Butyldiphenylsilyl-2,3,4-tri-O-benzoyl-b-d-mannopyranosyl azide
(7): Azide 6 (1.8 g, 4.8 mmol) was taken up in MeOH (20 mL) and
NaOMe (0.05 g, 0.96 mmol) was added and the mixture was stirred for
1 h. Dowex 50WX8 H+-resin (500 mg) was then added and the resulting
suspension was stirred until the solution was neutral. This was then fil-
tered and the solvent was removed to give the deprotected intermediate
(0.93 g, 94%) as a white solid; [a]D =ꢀ42.6 (c 0.2, CH3OH); 1H NMR
ACTHNUTRGNEUNG
(500 MHz, D2O): d=4.87 (d, 3J(H,H)=1.1 Hz, 1H; H-1), 3.03 (dd, 3J-
(H,H)=3.2, 1.1 Hz, 1H; H-2), 3.96 (dd, 2J(H,H)=12.3 Hz, 3J
AHCTUNGTREUNNGN ACHTUNGTRENNUNG ACHTUNGTRENNUNG
2
3
2.2 Hz, 1H; H-6a), 3.77 (dd, J
ACHUTGTNREN(UNG H,H)=12.3 Hz, JACHTNUGTRENNUNG
6b), 3.67 (dd, 3J
N
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
13C NMR (126 MHz, D2O): d=87.2 (C-1), 78.3 (C-5), 72.7 (C-3), 71.0 (C-
2), 66.4 (C-4), 60.9 ppm (C-6); IR (film): n˜ =3332, 2886, 2113, 1739, 1370,
1243, 1053, 1008 cmꢀ1; ESI-HRMS calcd for C8H13N3O6Na 228.0596,
found m/z (%) 228.0600 [M+Na]+. This intermediate (0.9 g, 4.4 mmol)
was dissolved in pyridine (50 mL) and the resulting solution was cooled
over an ice-bath. TBDPSCl (1.36 mL, 5.3 mmol) was then added in
a drop-wise manner and the reaction mixture was allowed to attain room
temperature and was stirred, overnight. The resulting suspension was
again cooled using an ice-bath and benzoyl chloride (1.12 mL, 9.7 mmol)
was added slowly and the mixture was allowed to warm to room temper-
ature and was stirred, overnight. Methanol (5 mL) was then added and
the resulting slurry was diluted with EtOAc (50 mL), washed twice with
1m HCl (50 mL), satd aqueous NaHCO3 (50 mL), brine (50 mL), dried
over Na2SO4, filtered and the solvent was removed under diminished
pressure. Flash chromatography of the residue (petroleum ether/EtOAc,
7:3) gave 7 (2.53 g, 76%) as a foam; [a]D =ꢀ19.5 (c 0.1, CH2Cl2);
1H NMR (500 MHz, CDCl3): d=8.15–7.13 (ms, 25H; Ar-H), 6.26 (aptt,
Experimental Section
Methyl 2,3,4-tri-O-acetyl-1-azido-1-deoxy-b-d-galactopyranuronate (4):
The bromide 3[31,32] (0.25 g, 0.63 mmol) and NaN3 (0.41 g, 6.3 mmol) were
placed in a Biotage microwave vial and then DMF (2.5 mL) was added
and the vial was sealed and the resulting suspension was placed in an ul-
trasonic bath and then sonicated for 15–20 min. The vial was opened and
the solution was poured on H2O (15 mL) and extracted twice with
EtOAc (15 mL). The combined organic extracts were washed with H2O
(40 mL), brine (40 mL), dried over Na2SO4, filtered and the solvent was
14842
www.chemeurj.org
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 14836 – 14851

Regiospecific Anomerisation
FULL PAPER
3J
5.56 (dd, J
H-1), 3.99–3.88 (m, 3H; H-6a, H-6b, H-5, overlapping peaks), 1.12 ppm
(s, 9H; C
(CH3)3); 13C NMR (126 MHz, CDCl3): d=165.7, 165.4, 164.9
(each COPh), 135.7, 135.5 (5ꢂAr-CH, overlapping peaks), 133.5 133.3
(2s), 132.6 (5ꢂAr-C), 130.2, 129.8, 129.7 (2s), 129.6, 129.3, 129.0, 128.8,
128.6, 128.5, 128.3, 127.8, 127.6 (20ꢂAr-CH, overlapping peaks), 85.4 (C-
1), 77.4 (C-5), 72.4 (C-3), 70.3 (C-2), 65.4 (C-4), 61.8 (C-6), 26.5 (C-
G
E
C, 2ꢂAr-CH, overlapping peaks), 127.7, 127.6 (4ꢂAr-CH, overlapping
peaks), 88.6 (C-1), 77.1 (C-5), 73.2 (C-3), 68.3 (C-4), 62.2 (C-6), 54.6 (C-
2), 26.6 (CACTHNURGTNE(UNG CH3)3, overlapping peaks), 23.3 (NHCOCH3), 19.2 ppm (C-
3
3
ACHTUGNTRENUN(NG CH3)3); IR (film): n˜ =3268, 2931, 2113, 1725, 1657, 1548, 1240,
1061 cmꢀ1; ESI-HRMS calcd for C38H40N4O7SiNa 701.2533, found m/z
(%) 701.2540 [M+Na]+.
2-Acetamido-6-O-tert-butyldiphenylsilyl-3,4-di-O-benzoyl-2-deoxy-b-d-
galactopyranosyl azide (12): Treatment of pentaacetyl-d-galactosamine
(3 g, 7.7 mmol) as described above for the glucosamine gave, via bromide
10, the intermediate azide (1.7 g, 59%) as a white solid; [a]D =ꢀ30.5 (c
ACHTUNGTRENNUNG(CH3)3, overlapping peaks), 19.2 ppm (CCAHUTNGTRENN(UGN CH3)3); IR (film): n˜ =2931,
2119, 1729, 1452, 1259, 1092, 1025 cmꢀ1
; ESI-HRMS calcd for
C43H41N3O8SiNa 778.2561, found m/z (%) 778.2553 [M+Na]+.
1
3
0.04, CH2Cl2); H NMR (500 MHz, CDCl3): d=5.56 (d, JCAHTUNGTRENNNUG
1H; NHCOCH3), 5.38 (dd, 3J
ACHTUNGTRENNUNG
2-Acetamido-6-O-tert-butyldiphenylsilyl-3,4-di-O-benzoyl-2-deoxy-b-d-
glucopyranosyl azide (11): Pentaacetyl-d-glucosamine (3 g, 7.7 mmol)
was suspended in CH2Cl2 (30 mL) and cooled to 08C. A 33% solution of
HBr in AcOH (30 mL) was added and the reaction mixture was stirred
for 5 h, keeping the reaction on ice. The reaction was then diluted with
CH2Cl2 (50 mL) and poured onto ice (100 mL). The layers were separat-
ed and the aqueous layer was washed with a further portion of CH2Cl2
(30 mL). The combined organic extracts were washed with ice (100 mL),
satd. aq. NaHCO3 (100 mL), brine (100 mL), dried over Na2SO4, filtered
and the solvent was removed under diminished pressure to give 9. Fresh-
ly prepared 9 was dissolved in CH2Cl2 (30 mL) and tetrabutylammonium
azide (4.38 g, 15.4 mmol) was added. The reaction mixture was stirred,
overnight, and the solvent was removed under diminished pressure. Flash
chromatography of the residue (EtOAc) gave the intermediate azide
(1.55 g, 54%) as a white solid; [a]D =ꢀ49.8 (c 0.15, CH2Cl2); 1H NMR
A
ACHTUNGTRENNUNG
4.19–4.13 (m, 2H; H-6a, H-6b, overlapping peaks), 4.07–3.97 (m, 2H; H-
5, H-2, overlapping peaks), 2.16 (s, 3H; NHCOCH3), 2.06 (s, 3H;
COCH3), 2.01 (s, 3H; COCH3), 1.99 ppm (s, 3H; COCH3); 13C NMR
(126 MHz, CDCl3): d=170.5, 170.4 (3ꢂCOCH3), 170.1 (NHCOCH3),
88.7 (C-1), 72.8 (C-5), 69.7 (C-3), 66.5 (C-4), 61.4 (C-6), 50.8 (C-2), 23.4
(NHCOCH3), 20.7, 20.6 ppm (2s) (3ꢂCOCH3); IR (film): n˜ =3267, 2932,
2113, 1723, 1549, 1315, 1240, 1061 cmꢀ1
; ESI-HRMS calcd for
C14H20N4O8Na 395.1179, found m/z (%) 395.1184 [M+Na]+. Treatment
of this azide (1.65 g, 4.4 mmol) as described above for the corresponding
GlcNAc derivative with MeOH (20 mL) and NaOMe (0.05 g, 0.9 mmol)
gave the unprotected GalNAc azide (0.93 g, 86%) as a white solid;
[a]D =ꢀ145.2 (c 0.04, CH3OH); 1H NMR (500 MHz, D2O): d=4.68 (d,
3J
(H,H)=9.3 Hz, 1H; H-1), 3.99 (dd, 3J
ACHTUGTNRENNUG CAHTUNGTRENN(UGN H,H)=3.1, 0.8 Hz, 1H; H-4),
3
(500 MHz, CDCl3): d=5.66 (d, 3J
(dd, 3J(H,H)=10.6, 9.4 Hz, 1H; H-3), 5.10 (dd, 3J
1H; H-4), 4.76 (d, 3J(H,H)=9.2 Hz, 1H; H-1), 4.27 (dd, 2J
12.4 Hz, 3J(H,H)=4.9 Hz, 1H; H-6a), 4.16 (dd, 2J(H,H)=12.4 Hz, 3J-
(H,H)=2.3 Hz, 1H; H-6b), 3.91 (aptdt, J(H,H)=10.6, 9.2 Hz, 1H; H-2),
3.79 (ddd, 3J
(H,H)=10.1, 4.9, 2.3 Hz, 1H; H-5), 2.10 (s, 3H; COCH3),
(H,H)=8.9 Hz, 1H; NHCOCH3), 5.24
(H,H)=10.1, 9.4 Hz,
(H,H)=
3.94 (dd, JACTHNUGNRTE(NUG H,H)=10.7, 9.3 Hz, 1H; H-2), 3.85–3.75 (m, 4H; H-6a, H-6b,
H-5, H-3, overlapping peaks), 2.07 ppm (s, 3H; NHCOCH3); 13C NMR
(126 MHz, D2O): d=174.9 (NHCOCH3), 89.0 (C-1), 77.2 (C-5), 70.7 (C-
3), 67.6 (C-4), 60.9 (C-6), 51.7 (C-2), 22.1 ppm (NHCOCH3); IR (film):
n˜ =3329, 2907, 2095, 1639, 1553, 1429, 1326, 1226, 1018 cmꢀ1; ESI-HRMS
calcd for C8H14N4O5Na 269.0862, found m/z (%) 269.0851 [M+Na]+.
This intermediate (0.9 g, 3.7 mmol) when treated with pyridine (15 mL)
and TBDPSCl (1.14 mL, 4.4 mmol) and then benzoyl chloride (0.93 mL,
8.0 mmol) as described above in preparation of 7 gave after chromatogra-
phy (petroleum ether/EtOAc, 6:4) the title compound 12 (1.79 g, 70%)
as a white foam; [a]D = +32.7 (c 0.1, CH2Cl2); 1H NMR (500 MHz,
CDCl3): d=8.07–8.02 (m, 2H; Ar-H), 7.87–7.83 (m, 2H; Ar-H), 7.66–
7.60 (m, 3H; Ar-H), 7.54–7.47 (m, 5H; Ar-H), 7.42–7.28 (m, 5H; Ar-H),
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
3
N
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
2.04 (s, 3H; COCH3), 2.03 (s, 3H; NHCOCH3), 1.98 ppm (s, 3H;
COCH3); 13C NMR (126 MHz, CDCl3): d=171.0, 170.6, 170.3 (each
COCH3), 169.2 (NHCOCH3), 88.4 (C-1), 74.0 (C-5), 72.1 (C-3), 68.0 (C-
4), 61.8 (C-6), 54.2 (C-2), 23.2 (NHCOCH3), 20.7, 20.6 ppm (2s) (3ꢂ
COCH3); IR (film): n˜ =3334, 2959, 2141, 2105, 1740, 1659, 1371, 1224,
1034 cmꢀ1; ESI-HRMS calcd for C14H20N4O8Na 395.1179, found m/z (%)
395.1187 [M+Na]+. This intermediate (1.5 g, 4.0 mmol) was dissolved in
MeOH (20 mL) and NaOMe (0.04 g, 0.8 mmol) was added. The reaction
was quenched after 1 h by the addition of Dowex 50WX8 H+-resin
(50 mg). The reaction was filtered and the solvent was removed to give
the unprotected GlcNAc derivative (0.89 g, 91%) as a white solid; [a]D =
ꢀ21.9 (c 0.07, CH3OH); 1H NMR (500 MHz, D2O): d=4.78 (d, 3J-
7.11 (t, 3J
(m, 2H; H-4, NHCOCH3, overlapping peaks), 4.80 (d, 3J
1H; H-1), 4.33 (aptdt, 3J(H,H)=11.1, 9.0 Hz, 1H; H-2), 4.06 (ddd, 3J-
(H,H)=7.4, 6.1, 1.2 Hz, 1H; H-5), 3.86–3.75 (m, 2H; H-6a, H-6b, over-
lapping peaks), 1.89 (s, 3H; NHCOCH3), 0.99 ppm (s, 9H; C(CH3)3);
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
13C NMR (126 MHz, CDCl3): d=170.5 (NHCOCH3), 166.4, 165.3 (2ꢂ
COPh), 135.5, 135.4, 133.5 (2s), 133.4 (6ꢂAr-CH, overlapping peaks),
132.7, 132.5 (2ꢂAr-C), 129.9 (2s), 129.8, 129.7 (6ꢂAr-CH, overlapping
peaks), 129.4, 128.8 (2ꢂAr-C), 128.6, 128.4, 127.8, 127.6 (8ꢂAr-CH, over-
lapping peaks), 89.0 (C-1), 75.7 (C-5), 71.0 (C-4), 67.1 (C-3), 61.1 (C-6),
A
E
ACHTUNGTREN(NUNG H,H)=2.2 Hz,
1H; H-6a), 3.79 (dd, 2J
ACHTUNGTRENNUNG
3.73 (dd, J
3.34 (m, 1H; H-5), 3.50 (dd, JACTHUNRTGNEUNG(H,H)=9.8, 8.7 Hz, 1H; H-4), 2.08 ppm (s,
3H; NHCOCH3); 13C NMR (126 MHz, D2O): d=174.7 (NHCOCH3),
88.6 (C-1), 77.8 (C-5), 73.6 (C-3), 69.4 (C-4), 60.5 (C-6), 55.0 (C-2),
22.0 ppm (NHCOCH3); IR (film): n˜ =3266, 2920, 2112, 1737, 1544, 1373,
1235, 1034 cmꢀ1; ESI-HRMS calcd for C8H15N4O5 233.1012, found m/z
51.4 (C-2), 26.6 (C
19.0 ppm (C(CH3)3); IR (film): n˜ =3994, 2860, 2115, 1722, 1657, 1272,
1106, 1068 cmꢀ1; ESI-HRMS calcd for C38H40N4O7SiNa 701.2533, found
m/z (%) 701.2525
[M+Na]+.
ACHTNUGRTNE(NUGN CH3)3, overlapping peaks), 23.3 (NHCOCH3),
AHCTUNGTRENNUNG
(%) 233.1019ACHTUNGTRENNUNG
[M+H]+. This polyhydroxylated intermediate (0.84 g,
AHCTUNGTRENNUNG
3.4 mmol) was taken up in pyridine (15 mL) and the resulting solution
was cooled and treated with TBDPSCl (1.1 mL, 4.1 mmol) followed by
benzoyl chloride (0.87 mL, 7.5 mmol) as described above in formation of
7. Flash chromatography (petroleum ether/EtOAc 6:4) gave 11 (1.8 g,
4,6-O-(1,1,3,3-Tetraisopropyl-1,3-disiloxanediyl)-b-d-glucopyranosyl azide
(16): Sodium methoxide (0.2 g, 4.0 mmol) was added to the azide 15
(7.5 g, 20.1 mmol) in MeOH (50 mL) and the mixture was stirred for 1 h
and then Dowex 50WX8 H+-resin (500 mg) was added and the resulting
suspension was stirred until the pH was 7. This mixture was then filtered
and the solvent was removed under diminished pressure to give b-d-glu-
copyranosyl azide (3.92 g, 95%) as a white solid; [a]D =ꢀ31.0 (c 0.3,
76%) as
a
white foam; [a]D =ꢀ51.2 (c 0.13, CH2Cl2); 1H NMR
(500 MHz, CDCl3): d=7.98–7.91 (m, 2H; Ar-H), 7.90–7.83 (m, 2H; Ar-
H), 7.75–7.68 (m, 2H; Ar-H), 7.61–7.45 (m, 4H; Ar-H), 7.42–7.32 (m,
6H; Ar-H), 7.18 (dd, 3J
ACHTUNGTRENNUNG
CH3OH); 1H NMR (500 MHz, D2O): d=4.75 (d, 3J
ACHTUNGTRENNUNG
H-1), 3.93 (dd, 2J
ACHUTNGRENNUG CAHTUNGTRENNUNG
(H,H)=12.4 Hz, 3J
AHCTUNGTRENNUNG
2J(H,H)=12.4 Hz, 3J
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
lapping peaks), 1.91 (s, 3H; NHCOCH3), 1.04 ppm (s, 9H; C
(CH3)3);
ACHTUNGTRENNUNG
d=90.9 (C-1), 79.0 (C-5), 76.9 (C-3), 73.6 (C-2), 69.9 (C-4), 61.4 ppm (C-
6); IR (film): n˜ =3303, 2881, 2125, 1472, 1377, 1263, 1064 cmꢀ1; ESI-
HRMS calcd for C6H12N3O5 206.0777, found m/z (%) 206.0772 [M+H]+.
To this intermediate (3.5 g, 17.1 mmol) in pyridine (50 mL) at 08C was
Chem. Eur. J. 2013, 19, 14836 – 14851
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
14843

P. V. Murphy et al.
added 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane (0.99 mL, 20.5 mmol)
and the mixture was allowed to warm to room temperature and was then
stirred for 5 h at which point MeOH (1 mL) was added and the solvent
removed under diminished pressure. The resulting residue was taken up
in EtOAc (50 mL) and washed with 1m HCl (50 mL), NaHCO3 (50 mL),
brine (50 mL), then dried over Na2SO4, filtered and the solvent removed
under diminished pressure. Flash chromatography of the residue (petro-
leum ether/EtOAc, 7:3) gave 16 (4.7 g, 61%) as a white solid; [a]D =
ꢀ80.7 (c 0.20, CH2Cl2); 1H NMR (500 MHz, CDCl3): d=4.58 (d, 3J-
2H; Ar-H), 7.91 (ddd, 3J
(m, 2H; Ar-H), 7.57–7.52 (m, 1H; Ar-H), 7.50 (dd, J
2H; Ar-H), 7.41 (aptq, 3J(H,H)=7.8 Hz, 3H; Ar-H), 7.35 (td, 3J
7.7, 4.2 Hz, 4H; Ar-H), 7.28–7.22 (m, 1H; Ar-H), 5.85 (aptt, 3J
9.5 Hz, 1H; H-3), 5.73 (aptt, 3J(H,H)=9.6 Hz, 1H; H-4), 5.58 (dd, 3J-
(H,H)=9.6, 7.7 Hz, 1H; H-2), 5.35 (d, 3J
(H,H)=7.7 Hz, 1H; H-1), 4.71
(dd, 2J(H,H)=12.1 Hz, 3J
(H,H)=3.2 Hz, 1H; H-6a), 4.57–4.47 (m, 2H;
H-1’, H6-b, overlapping peaks), 4.11 (ddd, 3J
(H,H)=10.0, 5.2, 3.2 Hz,
1H; H-5), 3.93 (aptt, 3J
(H,H)=8.5 Hz, 1H; H-2’), 3.89–3.79 (m, 3H; H-
3’, H-4’, H-5’, overlapping peaks), 3.75 (s, 3H; OCH3), 1.06–0.68 ppm (m,
28H; 4ꢂCH
(CH3)2, overlapping peaks); 13C NMR (126 MHz, CDCl3):
ACHTUNGTRENUN(NG H,H)=8.5, 4.0, 1.3 Hz, 4H; Ar-H), 7.82–7.71
3
AHCTUNGTRENNUNG
G
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
G
ACHTUNGTRENNUNG
R
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
N
G
ACHTUNGTREN(NUNG H,H)=2.1 Hz,
R
R
ACHTUNGTRENNUNG
A
E
d=168.1 (CO2CH3), 166.1, 165.8, 165.1 (2s) (4ꢂCOPh), 133.4, 133.2 (2s),
133.1, 129.9, 129.8, 129.7 (12ꢂAr-CH, overlapping peaks), 129.6, 129.2,
128.8, 128.0 (4ꢂAr-C), 128.4 (2s), 128.3, 128.2 (8ꢂAr-CH, overlapping
peaks), 100.0 (C-1), 88.4 (C-1’), 79.7 (C-3’), 77.2 (C-5’), 76.4 (C-2’), 74.0
(C-4’), 73.1 (C-3), 72.5 (C-2), 72.3 (C-5), 69.6 (C-4), 62.9 (C-6), 52.4
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
overlapping peaks), 13.6, 13.2, 12.5 ppm (2s) (4ꢂCH
N
(CO2CH3), 17.5, 17.4, 17.2 (2s), 17.1, 17.0 (2s) (8ꢂCHACHTUNGTRENNUNG
peaks), 12.8, 12.7, 12.3, 12.2 ppm (4ꢂCHAHCTUNGTRENNNUG
(film): n˜ =2946, 2119, 1728, 1452, 1249, 1089, 986 cmꢀ1; ESI-HRMS calcd
for C53H63N3O16Si2Na 1076.3645, found m/z (%) 1076.3652 [M+Na]+.
Methyl 1-azido-1-deoxy-3,4-O-(1,1,3,3-tetraisopropyl-1,3-disiloxanediyl)-
b-d-glucopyranuronate (17): p-TsOH.H2O (0.17 g, 0.9 mmol) was added
to diol 16 (2 g, 4.45 mmol), in DMF (25 mL) and the mixture was stirred
at room temperature for 5 h and it was then diluted with EtOAc
(50 mL), washed with H2O (2ꢂ25 mL), satd. aq. NaHCO3 (50 mL), brine
(50 mL), dried over Na2SO4, filtered and the solvent was removed under
diminished pressure. Flash chromatography of the residue (petroleum
ether/EtOAc 8:2) gave the 3,4-protected intermediate (1.87 g, 94%) as
Allyl 6-O-tert-butyldiphenylsilyl-2,3,4-tri-O-benzoyl-b-d-glucopyranoside
(22): Deacetylation of 21 (9 g, 23.2 mmol) as described for 15 gave the in-
termediate (4.4 g, 87%) as a white solid; [a]D =ꢀ35.0 (c 0.24, CH3OH);
1H NMR (500 MHz, D2O): d=5.99 (dddd, J=17.0, 10.5, 6.3, 5.5 Hz, 1H;
CH2CH=CH2), 5.40 (dq, 3J
CH2CH=CH2), 5.30 (dq, 3J(H,H)=10.5 Hz, 2J
CH2CH=CH2), 4.51 (d, J=8.0 Hz, 1H; H-1), 4.40 (ddt, 2J
1.4 Hz, 3J(H,H)=5.5 Hz, 1H; CH2CH=CH2), 4.24 (ddt, 2J
1.4 Hz, 3J(H,H)=6.3 Hz, 1H; CH2CHCH2), 3.93 (dd, 2J
(H,H)=12.3 Hz,
3J(H,H)=2.2 Hz, 1H; H-6a), 3.73 (dd, 2J(H,H)=12.3 Hz, 3J
(H,H)=
6.0 Hz, 1H; H-6b), 3.50 (aptt, 3J
(H,H)=9.2 Hz, 1H; H-3), 3.47–3.44 (m,
1H; H-5), 3.39 (dd, 3J(H,H)=9.9, 8.9 Hz, 1H; H-4), 3.30 ppm (dd, 3J-
(H,H)=9.3, 8.0 Hz, 1H; H-2); 13C NMR (126 MHz, D2O): d=133.2
A
ACHTUNGTREN(NGNU H,H) 1.5 Hz, 1H;
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
1
a clear oil; [a]D =ꢀ4.8 (c 0.17, CH2Cl2); H NMR (500 MHz, CDCl3): d=
A
ACHTUNGTRENNUNG
4.60 (d, 3J
A
G
E
A
R
ACHTUNGTRENNUNG
(H,H)=12.0 Hz, 3J
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
3
3
3.45 (ddd, J
G
E
ACHTUNGTRENNUNG
2.2 Hz, 1H; H-2), 2.44 (d, 3J
N
(CH2CHCH2), 118.7 (CH2CHCH2), 101.1 (C-1), 75.8 (C-5), 75.7 (C-3),
73.0 (C-2), 70.5 (CH2CHCH2), 69.6 (C-4), 60.7 ppm (C-6); IR (film): n˜ =
3295, 2915, 1664, 1458, 1365, 1109, 1073, 1022 cmꢀ1; ESI-HRMS calcd for
C9H16O6Na 243.0845, found m/z (%) 243.0852 [M+Na]+. This intermedi-
ate (10 g, 45.4 mmol) was treated with pyridine (100 mL), TBDPSCl
(14.1 mL, 54.5 mmol) and benzoyl chloride (34.82 mL, 299.7 mmol) as de-
scribed previously to give 22 (27.3 g, 78%) as a foam; [a]D =ꢀ21.1 (c 0.1,
CH2Cl2); 1H NMR (500 MHz, CDCl3): d=7.99–7.94 (m, 1H), 7.88–7.81
(m, 2H; Ar-H), 7.71–7.67 (m, 4H; Ar-H), 7.62–7.58 (m, 2H; Ar-H), 7.5–
7.48 (m, 2H; Ar-H), 7.44–7.27 (m, 9H; Ar-H), 7.25–7.21 (m, 2H; Ar-H),
5.88–5.78 (m, 2H; CH2CHCH2, C-3, overlapping peaks ), 5.62 (aptt, 3J-
ACHTUNGTRENNUNG(H,H)=6.8 Hz, 1H; OH), 1.16–0.86 ppm (m, 28H; 4ꢂCHACHTGNUTRENNUNG
lapping peaks); 13C NMR (126 MHz, CDCl3): d=89.5 (C-1), 79.8 (C-3),
78.4 (C-5), 73.9 (C-2), 72.1 (C-4), 61.9 (C-6), 17.3 (3s), 17.2 (2s), 17.1 (8ꢂ
CHACHTUNGTRENNUNG(CH3)2, overlapping peaks), 12.9, 12.8, 12.1 ppm (2s) (4ꢂCHACHTUGNTRENN(UNG CH3)2,
overlapping peaks); IR (film): n˜ =3349, 2868, 2114, 1464, 1248, 1052,
987 cmꢀ1; ESI-HRMS calcd for C18H37N3O6Si2Na 442.2349, found m/z
(%) 442.2356 [M+Na]+. This intermediate (1.8 g, 4.0 mmol) was dis-
solved in MeCN/H2O (60 mL, 3:1) and treated with BAIB (3.24 g,
10.1 mmol) and TEMPO (0.06 g, 0.4 mmol) as described above to give
the carboxylic acid, which when treated in DMF (25 mL) with NaHCO3
(0.5 g, 6.0 mmol) and methyl iodide (0.37 mL, 6.0 mmol) gave 17 (0.97 g,
51%) as a clear oil after chromatography (petroleum ether/EtOAc 9:1);
[a]D:ꢀ3.68 (c 0.06, CH2Cl2); 1H NMR (500 MHz, CDCl3): d=4.61 (d, 3J-
A
ACHTUNGTRNE(NUNG H,H)=9.7, 7.9 Hz, 1H; H-2), 5.25
A
ACHTUNGTRENNUNG
A
E
ACHTUNGTRENNUNG
2
3
A
ACHUTGTNREN(UNG H,H)=13.3 Hz, JACHTNUGTRENNUNG
3
peaks), 3.78 (s, 3H; OCH3), 3.68 (ddd, J
A
ACHTUNGTRENNUNG
3), 3.45 (td, 3J(H,H)=8.7, 1.9 Hz, 1H; H-2), 2.43 (d, 3J
1H; OH), 1.29–0.46 ppm (m, 28H; 4ꢂCH
N
ACHTUNGTRENNUNG
(3ꢂCOPh, overlapping peaks), 135.6, 135.5 (4ꢂAr-CH, overlapping
peaks), 133.6 (CH2CH=CH2), 133.2 (2ꢂAr-CH), 133.1 (2s) (Ar-C, 2ꢂAr-
CH, overlapping peaks), 133.0 (Ar-C), 129.8 (2s), 129.7, 129.6 (2s) (6ꢂ
Ar-CH, overlapping peaks), 129.5, 129.2, 129.0 (3ꢂAr-C),128.3 (2s),
128.2, 127.6 (2s) (11ꢂAr-CH, overlapping peaks), 117.6 (CH2CHCH2),
99.7 (C-1), 75.2 (C-5), 73.4 (C-3), 72.0 (C-2), 69.6 (CH2CH=CH2), 69.3
17.0 (2s) (8ꢂCH
ACHTUNGTRENNUNG(CH3)2, overlapping peaks), 12.9, 12.8, 12.2, 12.1 ppm
(4ꢂCHACHTUNGTRENNUNG(CH3)2, overlapping peaks); IR (film): n˜ =3441, 2867, 2125, 1785,
1736, 1464, 1251, 1081, 987 cmꢀ1; ESI-HRMS calcd for C19H37N3O7Si2Na
498.2068, found m/z (%) 498.2074 [M+Na]+.
(C-4), 62.8 (C-6), 26.6 (C
AHCTUNGTRENNUNG
ACHTUGNRTNE(NUNG CH3)3, overlapping peaks), 19.2 ppm (C-
Methyl
2-O-(2,3,4,6-tetra-O-benzoyl-b-d-glucopyranosyl)-1-azido-1-
(CH3)3); IR (film): n˜ =3071, 2857, 1729, 1451, 1259, 1091, 1026 cmꢀ1; ESI-
deoxy-3,4-O-(1,1,3,3-tetraisopropyl-1,3-disiloxanediyl)-b-d-glucopyranur-
onate (19): Compound 17 (0.25 g, 0.5 mmol), 18[13] (0.58 g, 0.8 mmol) and
CH2Cl2 (6 L) were added to a flame-dried flask containing freshly acti-
vated 4 ꢃ molecular sieves (0.6 g). The resulting suspension was stirred
at room temperature for 30 min before being cooled to 08C using an ice-
bath. TMSOTf (0.029 mL, 0.16 mmol) was then added and the reaction
mixture was allowed to attain room temperature over 1 h. Triethylamine
(0.25 mL) was added, the mixture filtered and the solvent was removed
under diminished pressure. Flash chromatography of the residue (petro-
leum ether/EtOAc 8:2) gave 19 (0.35 g, 67%) as a white foam; [a]D =
ꢀ22.6 (c 0.07, CH2Cl2); 1H NMR (500 MHz, CDCl3): d=8.06–8.01 (m,
HRMS calcd for C46H46O9SiNa 793.2809, found m/z (%) 793.2798
[M+Na]+.
1-O-Allyl-2,3,4-tri-O-benzoyl-b-d-glucopyranosiduronic acid, methyl
ester (23): The TBDPS derivative 22 (27.0 g, 35.0 mmol) was dissolved in
THF (250 mL) and the resulting solution was cooled using an ice-bath.
AcOH (4 mL, 70.0 mmol) and 1m TBAF in THF (70 mL, 70.0 mmol)
were added to this. The mixture was allowed to attain room temperature
and was stirred for 16 h and the product was adsorbed on silica gel. Flash
chromatography (petroleum ether/EtOAc 3:2) gave the intermediate al-
cohol (14.4 g, 77%) as a white solid; [a]D =ꢀ23.0 (c 0.2, CH2Cl2);
14844
www.chemeurj.org
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 14836 – 14851

Regiospecific Anomerisation
FULL PAPER
1H NMR (500 MHz, CDCl3): d=7.95 (apttt, 3J
G
tilled AcCl (0.13 mL, 1.84 mmol) was added to this and the reaction mix-
ture was allowed to attain room temperature. Methanol was added and
the solvent was removed under diminished pressure. Flash chromatogra-
phy of the residue (petroleum ether/EtOAc 9:1) gave 26 (0.58 g, 70%) as
Ar-H), 7.89–7.81 (m, 2H; Ar-H), 7.59–7.47 (m, 2H; Ar-H), 7.46–7.35 (m,
5H; Ar-H), 7.31–7.26 (m, 2H; Ar-H), 5.93 (aptt, 3J
(H,H)=9.7 Hz, 1H;
H-3), 5.81 (dddd, 3J
(H,H)=17.0, 10.7, 6.1, 5.0 Hz, 1H; CH2CHCH2),
5.60–5.39 (m, 2H; H-2, H-4, overlapping peaks), 5.26 (dq, 3J
(H,H)=
(H,H)=10.7 Hz,
(H,H)=7.9 Hz, 1H; H-1),
(H,H)=5.0, 1.6 Hz, 1H; CH2CHCH2),
(H,H)=6.1, 1.4 Hz, 1H; CH2CHCH2),
(H,H)=8.8, 1.9 Hz, 1H; H-6a), 3.83–3.68
(m, 2H; H-6b, H-5), 2.55 ppm (dd, 3J
(H,H)=8.8, 5.3 Hz, 1H; OH);
ACHTUNGTRENNUNG
1
a white solid; [a]D =ꢀ23.0 (c 0.18, CH2Cl2); H NMR (500 MHz, CDCl3):
2
17.0 Hz, J
G
G
ACTHNGUTRENNUG CAHTUNGTRENNUNG
d=4.56 (d, 3J(H,H)=8.7 Hz, 1H; H-1), 4.44 (dd, 2J(H,H)=12.0 Hz, 3J-
2J
(H,H)=1.4 Hz, 1H; CH2CHCH2), 4.89 (d, 3J
N
ACHUTGTNREN(UNG H,H)=12.0 Hz, JACHTNUGTRENNUNG
2
3
4.39 (ddt, 2J
4.19 (ddt, 2J
3
3J
2), 2.44 (d, 3J
0.93 ppm (m, 28H; 4ꢂCHACHTUNGTRENNUNG
G
ACHTUNGTRENNUNG
3.86 (ddd, 2J
ACHTUNGTRENNUNG
N
13C NMR (126 MHz, CDCl3): d=166.0, 165.8, 165.0 (3ꢂCOPh), 133.7
(Ar-CH, overlapping peaks), 133.4 (CH2CHCH2), 133.2 (2s) (2ꢂAr-CH),
129.9, 129.8, 129.7 (6ꢂAr-CH, overlapping peaks), 129.3, 128.8, 128.6 (3ꢂ
Ar-C), 128.5, 128.3 (2s) (6ꢂAr-CH), 117.7 (CH2CHCH2), 100.0 (C-1),
74.6 (C-5), 72.8 (C-3), 71.8 (C-4), 70.2 (CH2CHCH2), 69.6 (C-2),
61.4 ppm (C-6); IR (film): n˜ =3380, 2955, 1722, 1451, 1252, 1066,
1026 cmꢀ1; ESI-HRMS calcd for C30H28O9Na 555.1631, found m/z (%)
555.1637 [M+Na]+. This intermediate (14 g, 26.3 mmol) in MeC/H2O
(100 mL, 3:1) was oxidised, using BAIB (21.17 g, 65.7 mmol) and
TEMPO (0.4 g, 2.6 mmol), and the resulting acid was esterified in DMF
(80 mL) using NaHCO3 (3.3 g, 39.5 mmol) and methyl iodide (2.5 mL,
39.5 mmol) as described above to give 23 (8.7 g, 59%) as a foam; [a]D =
ꢀ40.0 (c 0.07, CH2Cl2); 1H NMR (500 MHz, CDCl3): d=7.98–7.92 (m,
(126 MHz, CDCl3): d=170.7 (OCOCH3), 89.6 (C-1), 79.7 (C-3), 76.1 (C-
5), 73.7 (C-2), 72.2 (C-4), 62.9 (C-6), 20.9, 17.3 (3s), 17.2 (3s), 17.1 (8ꢂ
CHACHTNURTGENNUG(CH3)2, overlapping peaks), 12.8, 12.7, 12.1 ppm (2s) (4ꢂCHACHTUNGTRENNUNG(CH3)2,
overlapping peaks); IR (film): n˜ =3504, 2947, 2868, 2114, 1725, 1463,
1250, 1028, 980 cmꢀ1; ESI-HRMS calcd for C20H39N3O7Si2Na 512.224,
found m/z (%) 512.2229 [M+Na]+.
2-O-(2,3,4-Tri-O-benzoyl-5-S-(methoxycarbonyl)-b-d-xylopyranosyl)-3,4-
O-(1,1,3,3-tetraisopropyl-1,3-disiloxanediyl)-6-O-acetyl-b-d-glucopyrano-
syl azide (27): Glycosidation with acceptor 26 (0.5 g, 1.0 mmol) and
donor 24 (0.91 g, 1.2 mmol) as described above gave 27 (0.88 g, 89%) as
a foam; [a]D =ꢀ4.0 (c 1.0, CHCl3); 1H NMR (500 MHz, CDCl3): d=7.91
(ddt, 3J(H,H)=17.1, 7.0, 1.4 Hz, 4H; Ar-H), 7.81 (dd, 3J
ACTHNUTRGENNUG ACHUTGNTREN(NUNG H,H)=8.4,
1.4 Hz, 2H; Ar-H), 7.54–7.48 (m, 2H; Ar-H), 7.44–7.33 (m, 5H; Ar-H),
7.28 (d, 3J(H,H)=7.8 Hz, 2H; Ar-H), 5.84 (aptt, 3J
(H,H)=9.2 Hz, 1H;
H-3’), 5.78 (aptt, 3J(H,H)=9.5 Hz, 1H; H-4’), 5.58 (dd, 3J
(H,H)=9.0,
7.6 Hz, 1H; H-2’), 5.34 (d, 3J(H,H)=7.5 Hz, 1H; H-1’), 4.54 (d, 3J-
(H,H)=12.0 Hz, 3J
(H,H)=2.2 Hz,
(H,H)=9.6 Hz, 1H; H-5’), 4.14 (dd, 3J
(H,H)=
4H; Ar-H), 7.90–7.83 (m, 2H; Ar-H), 7.52 (dddd, 3J
1.3 Hz, 2H; Ar-H), 7.47–7.43 (m, 1H; Ar-H), 7.38 (dddd, 3J
6.2, 3.5, 1.7 Hz, 4H; Ar-H), 7.33–7.28 (m, 2H; Ar-H), 5.90 (aptt, 3J-
(H,H)=9.3 Hz, 1H; H-3), 5.80 (dddd, 3J
(H,H)=17.0, 10.5, 6.4, 4.7 Hz,
1H; CH2CHCH2), 5.71 (aptt, 3J(H,H)=9.4 Hz, 1H; H-4), 5.57 (dd, 3J-
(H,H)=9.3, 7.3 Hz, 1H; H-2), 5.26 (dq, 3J(H,H)=17.0 Hz, 2J
(H,H)=
1.6 Hz, 1H; CH2CHCH2), 5.16 (dq, 3J(H,H)=10.5 Hz, 3J
(H,H)=1.4 Hz,
1H; CH2CHCH2), 4.92 (d, 3J(H,H)=7.3 Hz, 1H; H-1), 4.42 (ddt, 2J-
(H,H)=13.2 Hz, 3J(H,H)=4.8, 1.6 Hz, 1H; CH2CH=CH2), 4.35 (d, 3J-
(H,H)=9.4 Hz, 1H), 4.17 (ddt, 2J(H,H)=13.2 Hz, 3J
(H,H)=6.4, 1.4 Hz,
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
E
ACHTUNGTRENNUNG
1H; H-6a), 4.33 (d, 3J
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
A
R
ACHTUNGTRENNUNG
12.0 Hz, J
3J
4), 3.49 (ddd, J
1.08–0.72 ppm (m, 28H; 4ꢂCHAHCTNUGTRENNNUG
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
R
ACHTUNGTRENNUNG
(126 MHz, CDCl3): d=170.7 (COCH3), 167.0 (CO2CH3), 165.7, 165.0
(2s), (3ꢂCOPh), 133.4, 133.3 (2s)129.9, 129.8, 129.7 (9ꢂAr-CH, overlap-
ping peaks), 129.2, 128.8, 128.6 (3ꢂAr-C), 128.4, 128.3, 128.2 (6ꢂAr-CH,
overlapping peaks), 100.2 (C-1’), 88.4 (C-1), 79.8 (C-3), 78.0 (C-2), 75.6
(C-5), 73.1 (C-5’), 72.6 (C-3’), 72.5 (C-4), 72.1 (C-2’), 70.1 (C-4’), 62.8 (C-
6), 53.0 (CO2CH3), 20.9 (COCH3), 17.5 (2s) 17.4, 17.3, 17.2 (3s)17.1 (8ꢂ
1H; CH2CH=CH2), 3.70 ppm (s, 3H; CO2CH3); 13C NMR (126 MHz,
CDCl3): d=167.4 (CO2CH3), 165.6, 165.2, 165.0 (3ꢂCOPh), 133.4, 133.3,
133.2 (3ꢂAr-CH), 133.1 (CH2CH=CH2), 129.8 (3s) (6ꢂAr-CH, overlap-
ping peaks), 129.2, 128.7, 128.5 (3ꢂAr-C), 128.4 (2s), 128.3 (6ꢂAr-CH,
overlapping peaks), 118.0 (CH2CH=CH2), 99.6 (C-1), 72.9 (C-5), 72.0 (C-
3), 71.5 (C-2), 70.2 (CH2CHCH2), 70.1 (C-4), 52.9 ppm (CO2CH3); IR
(film): n˜ =3068, 1761, 1726, 1451, 1250, 1088 cmꢀ1; ESI-HRMS calcd for
C31H32NO10 578.2026, found m/z (%) 578.2031 [M+NH4]+.
CHACHTNURTGENNUG(CH3)2, overlapping peaks), 12.8, 12.7, 12.3 ppm (2s) (4ꢂCHACHTUNGTRENNUNG(CH3)2,
overlapping peaks); IR (film): n˜ =3073, 2952, 2120, 1727, 1686, 1452,
1248, 1091, 1067, 1026 cmꢀ1; ESI-HRMS calcd for C48H61O16N3Si2Na
1014.3488, found m/z (%) 1014.3491 [M+Na]+.
2,3,4-Tri-O-benzoyl-1-deoxy-1-(2,2,2-trichloro-1-iminoethoxy)-d-glucopyr-
anuronate, methyl ester (24): The allyl glycoside 23 (8.5 g, 15.1 mmol)
was dissolved in MeOH/CH2Cl2 (60 mL, 3:1) and PdCl2 (0.54 g,
3.0 mmol) was added and the mixture was stirred for 16 h at room tem-
perature. The resulting suspension was filtered through Celite and the
solvent was removed to give a foam. Flash chromatography (petroleum
ether/EtOAc 6:4) gave the hemiacetal (5.6 g, 10.8 mmol). This intermedi-
ate was dissolved in CH2Cl2 (50 mL) and cooled on an ice-bath and tri-
chloroacetonitrile (10.8 mL, 107.6 mmol) and DBU (0.5 mL) were added.
The mixture was stirred for 5 h and was directly subjected to flash chro-
matography (petroleum ether/EtOAc 7:3, 0.1% Et3N) to give 24 (6.95 g,
2,3,4-Tri-O-benzoyl-b-d-glucopyranosyl azide (29): Azide 28 (1 g,
4.87 mmol) prepared from 15 as described, was treated with TBDPSCl
(1.5 mL, 5.85 mmol) in pyridine and then benzoyl chloride (3.73 mL,
32.14 mmol) as described above, to give the silylated intermediate
(1.99 g, 54%) as
a
foam; [a]D =ꢀ25.9 (c 0.41, CH2Cl2); 1H NMR
(500 MHz, CDCl3): d=7.99–7.94 (m, 2H; Ar-H), 7.91–7.86 (m, 2H; Ar-
H), 7.86–7.81 (m, 2H; Ar-H), 7.74–7.69 (m, 2H; Ar-H), 7.61–7.56 (m,
2H; Ar-H), 7.56–7.50 (m, 2H; Ar-H), 7.45–7.34 (m, 7H; Ar-H), 7.34–7.27
(m, 3H; Ar-H), 7.23–7.18 (m, 2H; Ar-H), 5.86 (aptt, 3J
A
3
3
1H; H-3), 5.75 (aptt, J
8.8 Hz, 1H; H-2), 4.87 (d, JACHTGNUTRENNUNG
(H,H)=9.7 Hz, 1H; H-4), 5.47 (dd, J
a
white foam; [a]D =+44.4 (c 0.18, CH2Cl2); 1H NMR
3
69%) as
(500 MHz, CDCl3): d=8.68 (s, 1H; NH), 8.00–7.93 (m, 4H; Ar-H), 7.92–
7.85 (m, 2H; Ar-H), 7.58–7.49 (m, 2H; Ar-H), 7.46 (ddt, 3J
(H,H)=8.7,
7.2, 1.3 Hz, 1H; Ar-H), 7.42–7.30 (m, 5H; Ar-H), 6.91 (d, 3J
(H,H)=
3.6 Hz, 1H; H-1), 6.29 (aptt, 3J(H,H)=9.9 Hz, 1H; H-3), 5.76 (aptt, 3J-
(H,H)=9.9 Hz, 1H; H-4), 5.63 (dd, 3J
(H,H)=10.1, 3.6 Hz, 1H; H-2),
4.77 (d, 3J
(H,H)=10.5 Hz, 1H; H-5), 3.69 ppm (s, 3H; CO2CH3);
CACHTUNGTRENNUNG
13C NMR (126 MHz, CDCl3): d=165.8, 165.1, 164.8 (3ꢂCOPh), 135.6,
135.5, 133.4, 133.3, 133.2 (7ꢂAr-CH, overlapping peaks), 132.9, 132.8 (2ꢂ
Ar-C), 129.9, 129.8, 129.8, 129.7, 129.6 (8ꢂAr-CH, overlapping peaks),
129.0, 128.8, 128.7 (3ꢂAr-C), 128.4, 128.4, 128.3, 127.7, 127.6 (10ꢂAr-
CH, overlapping peaks), 88.1 (C-1), 77.3 (C-5), 73.1 (C-3), 71.5 (C-2),
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
13C NMR (126 MHz, CDCl3): d=167.2 (CO2CH3), 165.5, 165.2 (3ꢂ
COPh, overlapping peaks), 160.3 (OC(NH)CCl3), 133.6 (2s), 133.4, 129.9
(2s), 129.7 (9ꢂAr-CH, overlapping peaks), 128.7, 128.6 (2ꢂAr-C), 128.5
(2ꢂAr-CH, overlapping peaks), 128.4 (2s) (4ꢂAr-CH, Ar-C, overlapping
peaks), 92.9 (C-1), 70.9 (C-5), 70.2 (C-2), 69.6 (C-4), 69.3 (C-3), 53.0 ppm
68.5 (C-4), 62.3 (C-6), 26.6 (CACHTUNTRGENNUG(CH3)3), 19.2 ppm (CCAHTUNTGERN(NUGN CH3)3); IR (film): n˜ =
3071, 2858, 2116, 1731, 1451, 1245, 1088, 1068 cmꢀ1; ESI-HRMS calcd for
C43H42N3O8Si 756.2736, found m/z (%) 756.2742 [M+H]+. This inter-
mediate in THF (50 mL) was cooled over ice and AcOH (0.29 mL,
5.03 mmol) and 1m TBAF in THF (5.03 mL, 5.03 mmol) added and the
mixture stirred for 16 h. The product was adsorbed onto silica gel and
flash chromatography (petroleum ether/EtOAc 3:2) gave 29 (1.02 g,
79%) as a white solid; [a]D =+88.1 (c 0.2, CH2Cl2); 1H NMR (500 MHz,
(CO2CH3); IR (film): n˜ =3068, 1728, 1451, 1278, 1092, 1025 cmꢀ1
.
6-O-Acetyl-3,4-O-(1,1,3,3-tetraisopropyl-1,3-disiloxanediyl)-b-d-glucopyr-
anosyl azide (26): A solution of 25 (0.75 g, 1.7 mmol) in collidine (5 mL),
prepared from 16 as described above was cooled to ꢀ358C. Freshly dis-
ACTHNUTRGNEUNG
CDCl3): d=7.95 (td, 3J(H,H)=8.2, 1.4 Hz, 4H; Ar-H), 7.83 (dd, 3J-
Chem. Eur. J. 2013, 19, 14836 – 14851
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
14845

P. V. Murphy et al.
A
R
1.09–0.94 ppm (m, 28H; 4ꢂCHACTHGNUTERNNUG
(CH3)2, overlapping peaks); 13C NMR
A
(126 MHz, CDCl3): d=169.3 (COCH3), 167.5 (CO2CH3), 165.7, 165.3,
165.2 (3ꢂCOPh), 133.6, 133.4, 130.0, 129.9 (9ꢂAr-CH, overlapping
peaks), 129.4, 129.0, 128.9 (3ꢂAr-C), 128.6 (2s), 128.5 (6ꢂAr-CH, over-
lapping peaks), 101.7 (C-1’), 87.6 (C-1), 79.0 (C-5), 77.4 (C-3), 73.3 (C-4),
73.0 (C-5’), 72.6 (C-2), 72.3 (C-3’), 71.8 (C-2’), 70.3 (C-4’), 69.0 (C-6), 53.0
A
ACHTUNGTRENNUNG
3
3
ACHTUNGTRENNUNG(H,H)=9.8, 8.8 Hz, 1H; H-2), 4.96 (d, JACHTUNGTERN(NUGN H,H)=8.8 Hz,
G
N
ACHTUNGTRENNUNG
8.8, 5.6 Hz, 1H; OH); 13C NMR (126 MHz, CDCl3): d=166.0, 165.7,
165.0 (3ꢂCOPh), 133.8, 133.5, 133.4, 130.0, 129.9, 129.7 (9ꢂAr-CH, over-
lapping peaks), 128.7, 128.6 (2ꢂAr-C), 128.5, 128.4 (4ꢂAr-CH, overlap-
ping peaks), 128.3 (2s) (Ar-C, 2ꢂAr-CH, overlapping peaks), 88.4 (C-1),
77.0 (C-5), 72.6 (C-3), 71.2 (C-2), 69.0 (C-4), 61.1 ppm (C-6); IR (film):
(CO2CH3), 20.8 (COCH3), 17.6, 17.5, 17.3 (4s), 17.2 (8ꢂCH
ACHTUGNTRNEN(UNG CH3)2, over-
lapping peaks), 12.9, 12.8, 12.3, 12.2 ppm (4ꢂCH(CH3)2, overlapping
AHCTUNGTRENNUNG
peaks); IR (film): n˜ =2948, 2868, 2118, 1732, 1452, 1248, 1223, 1092, 1068,
1041, 1027, 984 cmꢀ1; ESI-HRMS calcd for C48H61O16N3Si2Na 1014.3488,
found m/z (%) 1014.3533 [M+Na]+.
n˜ =3491, 2122, 1723, 1450, 1244, 1088 cmꢀ1
; ESI-HRMS calcd for
2,4,6-Tri-O-benzoyl-3-O-(2,3,4-tri-O-benzoyl-5-S-(methoxycarbonyl)-b-d-
xylopyranosyl)-b-d-glucopyranosyl azide (32): Disaccharide 31 (0.25 g,
0.252 mmol) was added to 1.25m HCl in methanol (10 mL) at 08C and
the resulting solution was allowed to attain room temperature and stirred
for 16 h. The reaction mixture was cooled over an ice-bath, diluted with
MeOH (20 mL) and NaHCO3 was added. The resulting slurry was con-
centrated to dryness and the residue suspended was in pyridine and
cooled over an ice-bath. BzCl (0.18 mL, 1.5 mmol) was then added and
the reaction mixture was allowed to warm to room temperature and was
stirred, overnight. Methanol (0.5 mL) was added and the mixture was di-
luted with EtOAc (10 mL). This layer was washed with 1m HCl (2ꢂ5
mL), satd. aq. NaHCO3 (10 mL), brine (10 mL), dried over Na2SO4, fil-
tered and the solvent was removed under diminished pressure. Flash
chromatography of the residue (petroleum ether/EtOAc 6:4) gave 32
C27H27NO8Na 399.0903, found m/z (%) 399.0887 [M+Na]+.
2,3,4-Tri-O-benzoyl-6-O-(2,3,4-tri-O-benzoyl-5-S-(methoxycarbonyl)-b-d-
xylopyranosyl)-b-d-glucopyranosyl azide (30): The glycosidation of ac-
ceptor 29 (0.2 g, 0.39 mmol) and donor 24 (0.43 g, 0.58 mmol) was carried
out as previously described to give 30 (0.33 g, 84%) as a white solid;
[a]D =ꢀ10.1 (c 0.75, CH2Cl2); 1H NMR (500 MHz, CDCl3): d=8.06–7.97
(m, 2H), 7.98–7.90 (m, 4H), 7.90–7.85 (m, 4H), 7.79–7.74 (m, 2H), 7.52
(t, 3J
2H), 7.29–7.24 (m, 3H), 5.91 (aptt, 3J
(aptt, 3J(H,H)=9.6 Hz, 1H; H-3), 5.68 (aptt, 3J
4’), 5.54 (dd, 3J(H,H)=9.3, 7.1 Hz, 1H; H-2’), 5.38 (aptt, 3J
9.8 Hz, 1H; H-4), 5.35 (aptt, 3J(H,H)=9.3 Hz, 1H; H-2), 5.04 (d, 3J-
(H,H)=7.3 Hz, 1H; H-1), 4.65 (d, 3J
(H,H)=8.8 Hz, 1H; H-1’), 4.35 (d,
3J(H,H)=9.4 Hz, 1H; H-5’), 4.13 (dd, 2J(H,H)=12.0 Hz, 3J
(H,H)=
1.9 Hz, 1H; H-6a), 4.06 (ddd, 3J
(H,H)=9.8, 7.4, 1.9 Hz, 1H; H-5), 3.90
(dd, 2J(H,H)=12.0 Hz, 3J
(H,H)=7.4 Hz, 1H; H-6b), 3.66 ppm (s, 3H;
A
ACHTUNGTREN(NUNG H,H)=7.7 Hz,
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
E
U
(0.15 g, 63%) as
a
glass; [a]D =ꢀ15.6 (c 1.25, CH2Cl2); 1H NMR
E
(500 MHz, CDCl3): d=8.00 (dd, 3J
ACTHNGUTERN(UNG H,H)=8.4, 1.4 Hz, 2H; Ar-H), 7.95–
A
U
7.90 (m, 4H; Ar-H), 7.88 (ddd, 3J
7.79–7.75 (m, 2H; Ar-H), 7.55–7.50 (m, 4H; Ar-H), 7.48–7.27 (m, 14H;
Ar-H), 5.91 (aptt, 3J(H,H)=9.3 Hz, 1H; H-3’), 5.79 (aptt, 3J
(H,H)=
9.6 Hz, 1H; H-3), 5.68 (aptt, 3J(H,H)=9.3 Hz, 1H; H-4’), 5.54 (dd, 3J-
(H,H)=9.2, 7.3 Hz, 1H; H-2’), 5.38 (aptt, 3J
(H,H)=9.8 Hz, 1H; H-2),
5.35 (dd, 3J(H,H)=9.7, 8.7 Hz, 1H; H-4), 5.04 (d, 3J
(H,H)=7.3 Hz, 1H;
ACHTUNGTRNE(NUNG H,H)=8.4, 3.0, 1.4 Hz, 4H; Ar-H),
CO2CH3); 13C NMR (126 MHz, CDCl3): d=167.4 (CO2CH3), 165.7,
165.7, 165.4, 165.3, 165.2, 165.1 (6ꢂCOPh), 133.8, 133.6, 133.6, 133.5,
130.0, 130.0, 130.0, 129.9 (18ꢂAr-CH, overlapping peaks), 129.3, 128.9,
128.9, 128.9, 128.7 (5ꢂAr-C), 128.6, 128.6 (8ꢂAr-CH, Ar-C, overlapping
peaks), 128.5, 128.4 (4ꢂAr-CH, overlapping peaks), 101.6 (C-1), 88.0 (C-
1’), 76.6 (C-5), 73.0 (C-5’), 72.8 (C-3), 72.0 (C-3’), 71.6 (C-2’), 71.4 (C-2),
70.1 (C-4’), 69.2 (C-4), 68.8 (C-6), 53.0 ppm (CO2CH3); IR (film): n˜ =
2956, 2120, 1727, 1452, 1245, 1087, 1067, 1026 cmꢀ1; ESI-HRMS calcd for
C55H45O17N3Na 1042.2647, found m/z (%) 1042.2656 [M+Na]+.
G
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
3
3
H-1’), 4.65 (d, JACHTNUGTREN(NUNG H,H)=8.8 Hz, 1H; H-1), 4.35 (d, JACHTGNUTRENNUNG
H-5’), 4.13 (dd, 2J
(H,H)=12.0 Hz, 3J
E
3
2
3
(ddd, J
(H,H)=9.7, 7.6, 1.9 Hz, 1H; H-5), 3.90 (dd, J
G
AHCTUNGTRENNUNG
(H,H)=7.6 Hz, 1H; H-6b), 3.66 ppm (s, 3H; CO2CH3); 13C NMR
(126 MHz, CDCl3): d=167.2 (CO2CH3), 165.6, 165.5, 165.3, 165.2, 165.0,
164.9 (6ꢂCOPh), 133.6, 133.5, 133.4, 133.3, 129.9 (2s), 129.8 (2s), 129.7
(18ꢂAr-CH, overlapping peaks), 129.1, 128.8, 128.7 (2s), 128.6 (5ꢂAr-C,
overlapping peaks), 128.5, 128.4 (2s) (8ꢂAr-CH, Ar-C, overlapping
peaks), 128.3 (2s) (4ꢂAr-CH, overlapping peaks), 101.5 (C-1’), 87.8 (C-
1), 76.5 (C-5), 72.8 (C-5’), 72.6 (C-3), 71.8 (C-3’), 71.5 (C-2’), 71.2 (C-2),
70.0 (C-4’), 69.1 (C-4), 68.6 (C-6), 52.9 ppm (CO2CH3); IR (film): n˜ =
2956, 2120, 1714, 1451, 1247, 1088, 1068, 1026 cmꢀ1; ESI-HRMS calcd for
C55H45O17N3Na 1042.2647, found m/z (%) 1042.2646 [M+Na]+.
2-O-Acetyl-3-O-(2,3,4-tri-O-benzoyl-5-S-(methoxycarbonyl)-b-d-xylopyr-
anosyl)-4,6-O-(1,1,3,3-tetraisopropyl-1,3-disiloxanediyl)-b-d-glucopyrano-
syl azide (31): A solution of 16 (0.5 g, 1.1 mmol) in collidine (2.5 mL)
was cooled to ꢀ358C. Freshly distilled AcCl (0.087 mL, 1.23 mmol) was
added to this and the reaction mixture was allowed to attain room tem-
perature and stirred for 16 h. MeOH was added and the solvent was re-
moved and flash chromatography of the residue (petroleum ether/EtOAc
9:1) gave the 2-O-acetylated intermediate (0.42 g, 78%); [a]D =ꢀ1.8 (c
0.1, CH2Cl2); 1H NMR (500 MHz, CDCl3): d=4.92–4.84 (m, 1H; H-2),
4.53 (d, 3J
(m, 3H; H-6b, H-4, H-3, overlapping peaks), 3.45 (dddd, 3J
5.2, 2.8, 1.3 Hz, 1H; H-5), 2.09 (s, 3H; COCH3), 1.98–1.91 (m, 1H; OH),
1.13–0.89 (m, 28H; 4ꢂCH
(CH3)2, overlapping peaks); 13C NMR
G
2,3-O-(1,1,3,3-Tetraisopropyl-1,3-disiloxanediyl)-6-O-acetyl-b-d-glucopyr-
anosyl azide (33): Azide 28 (1.5 g, 7.3 mmol) was dissolved in DMF
(15 mL) and 2,2-dimethoxypropane (1.78 mL, 14.6 mmol) and p-toluene-
sulfonic acid (0.14 g, 0.73 mmol) were added and the reaction mixture
was stirred at room temperature for 3 h. Triethylamine (1 mL) was added
and the solvent was removed and the residue was dissolved in pyridine
(15 mL) and the mixture was cooled over ice. 1,3-Dichloro-1,1,3,3-tetra-
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
(126 MHz, CDCl3): d=169.2 (COCH3), 87.9 (C-1), 78.4 (C-5), 77.3 (C-4),
72.7 (C-3), 72.5 (C-2), 61.9 (C-6), 20.6 (COCH3), 17.2 (2s), 17.1 (4s) (8ꢂ
CHACHTUNGTRENNUNG(CH3)2, overlapping peaks), 12.8 (2s), 12.1, 12.0 ppm (4ꢂCHACHTUGNTRENN(UNG CH3)2,
overlapping peaks); IR (film): n˜ =3533, 2943, 2866, 2121, 1729, 1462,
1243, 980 cmꢀ1; ESI-HRMS calcd for C20H39N3O7Si2Na 512.224, found
m/z (%) 512.2232 [M+Na]+. Glycosidation of this intermediate (0.4 g,
0.8 mmol) with 24 (0.91 g, 1.2 mmol) gave 31 (0.65 g, 82%) after chroma-
tography (petroleum ether/EtOAc 8:2) as a foam; [a]D =ꢀ24.1 (c 0.1,
ACHTUNGERTNiNUNG sopropyldisiloxane (2.88 g, 9.13 mmol) was added and the mixture stirred
for 16 h at room temperature. Methanol (1 mL) was added followed by
EtOAc (50 mL) and this layer was washed with 1m HCl (2ꢂ50 mL),
satd. aq. NaHCO3 (50 mL), brine (50 mL), dried over Na2SO4, filtered
and the solvent was removed under diminished pressure. Flash chroma-
tography of the residue (petroleum ether/EtOAc 95:5) gave the protected
intermediate (2.53 g, 71%) as a clear oil; [a]D =+78.8 (c 0.25, CH2Cl2);
1
3
CH2Cl2); H NMR (500 MHz, CDCl3): d=7.98 (dd, J
2H; Ar-H), 7.93 (dd, 3J
(H,H)=8.3, 1.4 Hz, 2H; Ar-H), 7.51 (dd, 3J
H), 7.47–7.42 (m, 1H), 7.38 (q, 3J(H,H)=7.9 Hz, 4H; Ar-H), 7.30 (t, 3J-
(H,H)=7.8 Hz, 2H; Ar-H), 5.89 (aptt, 3J
(H,H)=9.3 Hz, 1H; H-3’), 5.71
(aptt, 3J(H,H)=9.4 Hz, 1H; H-4’), 5.53 (dd, 3J
(H,H)=9.3, 7.4 Hz, 1H;
H-2’), 5.09 (d, J
H-2), 4.36 (d, 3J
(H,H)=9.5 Hz, 1H; H-5), 4.28–4.19 (m, 2H; H-6a, H-1,
overlapping peaks), 3.85 (dd, 2J(H,H)=12.2 Hz, 3J
(H,H)=7.3 Hz, 1H;
H-6b), 3.70 (s, 3H; CO2CH3), 3.63 (dd, 3J
(H,H)=9.1, 7.7 Hz, 1H; H-3),
3.59–3.49 (m, 2H; H-5, H-4, overlapping peaks), 2.06 (s, 3H; COCH3),
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
A
U
1H NMR (500 MHz, CDCl3): d=4.57 (d, 3J
3.95 (dd, 2J(H,H)=10.8 Hz, 3J(H,H)=5.3 Hz, 1H; H-6a), 3.75 (aptt, 2J-
(H,H)=10.5 Hz, 1H; H-6b), 3.68 (dd, 3J
(H,H)=8.9, 7.9 Hz, 1H; H-3),
3.55–3.49 (m, 2H; H-2, H-4, overlapping peaks), 3.32 (td, 3J
(H,H)=10.0,
5.3 Hz, 1H; H-5), 1.47 (s, 3H; C(CH3)2), 1.38 (s, 3H; C(CH3)2), 1.13–
(CH3)2, overlapping peaks); 13C NMR
(CH3)2), 91.3 (C-1), 78.1 (C-2), 76.6 (C-3),
(CH3)2), 17.3, 17.2, 17.1
(CH3)2, overlapping peaks), 12.9, 12.8, 12.2,
ACHTUNGERTN(NUNG H,H)=8.2 Hz, 1H; H-1),
N
A
ACHTUNGTRENNUNG
A
U
A
ACHTUNGTRENNUNG
A
G
ACHTUNGTRENNUNG
3
3
G
A
A
ACHTUNGTRENNUNG
E
0.99 ppm (m, 28H; 4ꢂCH
(126 MHz, CDCl3): d=99.5 (CACHTGNUTRENNUNG
ACHTUNGTRENNUNG
A
U
R
72.7 (C-4), 69.5 (C-5), 62.0 (C-6), 28.9, 19.0 (C
(2s), 17.0, 16.8 (8ꢂCH
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
14846
www.chemeurj.org
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 14836 – 14851

Regiospecific Anomerisation
FULL PAPER
12.0 ppm (4ꢂCH
G
2H; Ar-H), 7.58 (dd, 3J
ACHTNUGETRNNU(G H,H)=8.3, 1.4 Hz, 2H; Ar-H), 7.55–7.45 (m,
2115, 1738, 1465, 1064, 983 cmꢀ1; ESI-HRMS calcd for C21H42N3O6Si2
488.7451, found m/z (%) 488.7458 [M+H]+. This intermediate (2.5 g,
5.1 mmol) was dissolved in MeOH and Amberlyst 15H+ (3.0 g) was
added and the mixture was stirred for 5 h. The resin was filtered off and
the solvent was removed and flash chromatography of the residue (petro-
leum ether/EtOAc, 8:2) gave the required 2,3-O-silylated intermediate
3H; Ar-H), 7.45–7.33 (m, 7H; Ar-H), 7.29–7.17 (m, 8H; Ar-H), 5.78–5.67
(m, 3H,H-3, H-4’, H-3’, overlapping peaks), 5.54–5.48 (m, 2H; H-2’, H4’,
ACTHNUTRGNEUNG
overlapping peaks), 5.07 (d, 3J(H,H)=7.6 Hz, 1H; H-1’), 4.87 (d, 3J-
A
R
ACHTUNGTREN(NUNG H,H)=3.0 Hz,
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
(1.88 g, 82%) as
a
wax; [a]D =ꢀ18.0 (c 0.11, CH2Cl2); 1H NMR
lapping peaks), 3.73 ppm (s, 3H; CO2CH3); 13C NMR (126 MHz, CDCl3):
d=166.7 (CO2CH3), 166.0, 165.5, 165.1, 165.0, 164.9, 164.7 (6ꢂCOPh),
133.4 (2s), 133.3, 133.1, 132.9, 129.8 (2s), 129.7 (3s), 129.6 (18ꢂAr-CH,
overlapping peaks), 129.5, 128.8, 128.7, 128.5 (3s) (6ꢂAr-C), 128.4 (2s),
128.3 (2s), 128.2, 128.1 (12ꢂAr-CH, overlapping peaks), 100.8 (C-1’),
88.8 (C-1), 77.7 (C-2), 73.9 (C-5 and C-3, overlapping peaks), 73.0 (C-5’),
72.2 (C-3’), 71.6 (C-2’), 70.0 (C-4’), 69.0 (C-4), 62.8 C-6), 53.0 ppm
(CO2CH3); IR (film): n˜ =2945, 2867, 2120, 1724, 1452, 1248, 1092, 1066,
1027, 986, 702 cmꢀ1; ESI-HRMS calcd for C55H45O17N3Na 1042.2647,
found m/z (%) 1042.2631 [M+Na]+.
ACTHNUTRGNEUNG
(500 MHz, CDCl3): d=4.61 (d, 3J(H,H)=8.1 Hz, 1H; H-1), 3.95 (dd, 2J-
A
R
ACHTUNGTRNE(NUNG H,H)=
A
ACHTUNGTRENNUNG
3
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
peaks); IR (film): n˜ =3372, 2945, 2868, 2117, 1738, 1464, 1143, 1036,
986 cmꢀ1; ESI-HRMS calcd for C18H37N3O6Si2Na 442.2349, found m/z
(%) 442.2354 [M+Na]+. This intermediate (1.5 g, 3.35 mmol) was treated
with freshly distilled AcCl (0.26 mL, 3.69 mmol) in collidine (7.5 mL) as
previously described and gave 33 (0.97 g, 59%) after flash chromatogra-
phy (petroleum ether/EtOAc 9:1); [a]D =ꢀ25.6 (c 0.25, CH2Cl2);
2,3,4-Tri-O-benzoyl-1-deoxy-1-(2,2,2-trichloro-1-iminoethoxy)-d-galacto-
pyranuronate, methyl ester (37): The compound 36[33] (10 g, 0.017 mol) in
CH2Cl2 (100 mL) and H2O (40 mL) was treated with TEMPO (0.5 g) and
BAIB (16.2 g, 0.05 mol) as described above to give the galacturonic acid
(9.5 g, 91%). Some of this acid (3 g, 4.9 mmol) was dissolved in DMF
(40 mL) and treated with NaHCO3 (0.8 g, 9.5 mmol) and MeI (0.50 mL,
7.2 mmol) as described above and gave after chromatography (petroleum
ether/EtOAc 3:1) the methyl ester as a white solid (2.58 g, 86%, mixture
of anomers, a/b=3:1). Analytical data for the a anomer: 1H NMR
1H NMR (500 MHz, CDCl3): d=4.57 (d, 3J
ACHTUNGTRENNUNG
4.42 (dd, 2J
ACHTUNGTRENNUNG ACHTUNGTRENNUNG
(H,H)=12.2 Hz, 3J
A
R
ACHTUNGTRENNUNG
(500 MHz, CDCl3): d=8.10–8.03 (m, 4H; Ar-H), 7.89 (d, 3J
7.8 Hz, 2H; Ar-H), 7.83 (d, 3J(H,H)=6.9 Hz, 2H; Ar-H), 7.61 (t, 3J-
(H,H)=7.3 Hz, 1H; Ar-H), 7.59–7.51 (m, 1H; Ar-H), 7.51–7.40 (m, 6H;
Ar-H), 7.30 (m, 4H; Ar-H), 6.27 (m, 2H; H4 and H1), 6.15–6.08 (m, 1H;
ACHTUNGTRENNUNG(H,H)=
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
(126 MHz, CDCl3): d=171.1 (COCH3), 90.8 (C-1), 80.0 (C-3), 76.4 (C-2),
75.1 (C-5), 70.2 (C-4), 63.1 (C-6), 20.9 (COCH3), 17.3, 17.2 (3s), 17.1, 17.0
3
H2), 5.78 (dd, JACTHNUTRGNEUNG(H,H)=10.3, 3.3 Hz, 1H; H3), 4.84 (s, 1H; H5), 3.71 ppm
(s, 3H; CH3); 13C NMR (125 MHz, CDCl3): d=165.9, 165.4, 165.2, 164.70
(each C=O), 133.9, 133.6, 133.5, 133.4 (each CH), 130.3, 130.1, 129.8,
129.7 (each CH), 128. 8, 128.7, (each C), 128.6, 128.5, 128.4, 128.3 (each
CH), 92.6 (C-1), 73.7 (C-5), 71.2 (C-3), 69.0 (C-4), 68.2 (C-2), 52.9 ppm
(CH3); ESI-HRMS calcd for C35H28O11Na 647.1529, found m/z (%)
647.1533 [M+Na]+. This intermediate (2 g, 3.2 mmol) was dissolved in
CH2Cl2 (5 mL) and cooled to 08C and 33% HBr in AcOH (8 mL) was
then added and the mixture was stirred at room temperature for 6 h. The
mixture was then diluted with EtOAc, washed with water, satd. aq.
NaHCO3, water, brine, dried over Na2SO4, and the solvent was removed
under diminished pressure to give the glycosyl bromide as a colourless
oil. This was taken up in acetone (90 mL) and water (10 mL) and
Ag2CO3 (530 mg, 1.9 mmol) were added and the mixture was stirred for
16 h at room temperature. The mixture was filtered through Celite, which
was subsequently rinsed with CH2Cl2. The combined filtrate were dried
over Na2SO4, and the solvent was removed under diminished pressure.
Flash chromatography (petroleum ether/EtOAc 2:1) gave the hemiacetal
as a white solid (1.21 g, 73% over 2 steps) and as mixture of anomers
(a/b=3:1). Analytical data for the a anomer: 1H NMR (500 MHz,
(8ꢂCH
(CH3)2, overlapping peaks); IR (film): n˜ =3484, 2946, 2869, 2116, 1736,
1464, 1245, 1149, 1039, 985 cmꢀ1; ESI-HRMS calcd for C20H39N3O7Si2Na
512.224, found m/z (%) 512.2219
[M+Na]+.
ACHTUNGTRENNUNG(CH3)2, overlapping peaks), 12.8 (2s), 12.1 (2s), 12.1 ppm (4ꢂCH-
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
2,3-O-(1,1,3,3-Tetraisopropyl-1,3-disiloxanediyl)-4-O-(2,3,4-tri-O-benzoyl-
5-S-(methoxycarbonyl)-b-d-xylopyranosyl)-6-O-acetyl-b-d-glucopyranosyl
azide (34): Glycosidation of 33 (0.5 g, 1.02 mmol) with donor 24 (1.13 g,
1.53 mmol) as previously described gave 34 (0.67 g, 66%) after chroma-
tography (petroleum ether/EtOAc 8:2) as a glass; [a]D =ꢀ75.3 (c 0.3,
CH2Cl2); 1H NMR (500 MHz, CHCl3): d=7.98–7.90 (m, 4H; Ar-H),
7.86–7.81 (m, 2H; Ar-H), 7.58–7.51 (m, 2H; Ar-H), 7.48–7.36 (m, 6H;
3
3
Ar-H), 7.30 (t, J
1H; H-3’), 5.69 (aptt, 3J
9.6, 7.8 Hz, 1H; H-2’), 4.92 (d, 3J
(H,H)=8.3 Hz, 1H; H-1), 4.35 (dd, 2J
1H; H-6a), 4.28 (d, 3J(H,H)=9.7 Hz, 1H; H-5’), 4.14 (dd, 3J
12.2 Hz, 3J(H,H)=4.9 Hz, 1H; H-6b), 3.80 (aptt, 3J
(H,H)=8.4 Hz, 1H;
H-3), 3.76–3.69 (m, 4H; CO2CH3, H-4, overlapping peaks), 3.49 (aptt, J-
(H,H)=8.3 Hz, 1H; H-2), 3.42 (ddd, 3J
(H,H)=10.0, 4.9, 2.0 Hz, 1H; H-
5), 2.03 (s, 3H; COCH3), 1.23–1.04 ppm (m, 28H; 4ꢂCH(CH3)2, overlap-
G
ACHTUNGTRENNUNG
R
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
G
E
ACHTUNGTRENNUNG
G
ACHTUNGTRENNUNG
G
ACHTUNGTRENNUNG
3
CDCl3): d=8.00 (dd, 3J
AHCTUNGTRENNUNG
(H,H)=17.5, 7.8 Hz, 4H; Ar-H), 7.81 (d, 3J-
E
ACHTUNGTRENNUNG
3
AHCTUNGTRENNUNG
A
ping peaks); 13C NMR (126 MHz, CDCl3): d=170.3 (COCH3), 166.5
(COCH3), 165.5, 164.9, 164.6 (3ꢂCOPh), 133.5, 133.4, 133.3, 129.8 (2s)
(9ꢂAr-CH, overlapping peaks), 128.7, 128.6 (3ꢂAr-C, overlapping
peaks), 128.5, 128.4, 128.3 (6ꢂAr-CH, overlapping peaks), 100.9 (C-1’),
90.5 (C-1), 77.8 (C-3), 77.1 (C-4), 74.6 (C-5), 73.7 (C-5’), 72.3 (C-3’), 71.8
(C-2’), 70.2 (C-4’), 61.9 (C-6), 52.8 (CO2CH3), 29.7, 20.8, 17.4, 17.3, 17.2
3
3J
7.37 (t, 3J
1H; H1), 6.06 (dd, 3J
(dd, 3J
(H,H)=10.8, 3.0 Hz, 1H; H2), 5.16 (s, 1H; H5), 3.71 (s, 3H; CH3),
G
ACHTUNGTNER(NUNG H,H)=7.7 Hz, 3H; Ar-H Ar-H),
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
3.55 ppm (s, 1H; OH); 13C NMR (125 MHz, CDCl3): a=167.8, 165.9,
165.5, 165.2 (each C=O), 133.5 (2s), 133.2 (each CH), 129.9, 129.8, 129.7
(each C), 129.1, 129.0 (2s), 128.6, 128.5, 128.3 (each CH), 91.2 (C-1), 69.9
(C-4), 68.8 (2s) (C-5 and C-2), 67.6 (C-3), 52.8 ppm (CH3); ESI-HRMS
calcd for C34H28O10Na 619.1580, found m/z (%) 619.1591 [M+Na]+. This
hemiacetal (540 mg, 1.0 mmol) was dissolved in CH2Cl2 (20 mL) and
cooled to 08C And Cl3CCN (1.0 mL, 10.3 mmol) was added followed by
DBU (6 drops). The mixture was stirred at 08C for 5 h, concentrated to
5 mL and subsequent chromatography of the residue (petroleum ether/
EtOAc 2:1) gave the title compound 37 (425 mg, 61%) as a white solid;
(2s), 17.1 (2s), 17.0 (8ꢂCHACHTUNRGTNEUNG(CH3)2, overlapping peaks), 12.8 (2s), 12.1,
11.6 ppm (4ꢂCHACHTUNGTRENNUNG(CH3)2, overlapping peaks); IR (film): n˜ =3072, 2955,
2118, 1728, 1691, 1451, 1248, 1090, 1067, 1025 cmꢀ1; ESI-HRMS calcd for
C48H61O16N3Si2Na 1014.3488, found m/z (%) 1014.3469 [M+Na]+.
2,3,6-Tri-O-benzoyl-4-O-(2,3,4-tri-O-benzoyl-5-S-(methoxycarbonyl)-b-d-
xylopyranosyl)-b-d-glucopyranosyl azide (35): Removal of the acetyl
group and silyl protecting group from 34 (0.3 g, 0.3 mmol) as described
above gave 35 (0.17 g, 54%) as a glass after chromatography (petroleum
ether/EtOAc 6:4); [a]D =ꢀ56.6 (c 1.15, CH2Cl2); 1H NMR (500 MHz,
1H NMR (500 MHz, CDCl3): d=8.69 (s, 1H; NH), 8.03 (d, 3J
7.7 Hz, 2H; Ar-H), 7.94 (d, 3J(H,H)=7.8 Hz, 2H; Ar-H), 7.82 (d, 3J-
(H,H)=7.8 Hz, 2H; Ar-H), 7.61 (t, 3J
(H,H)=7.4 Hz, 1H; Ar-H), 7.54–
ACHTUNGTRENNUNG(H,H)=
CDCl3): d=8.02–7.98 (m, 2H; Ar-H), 7.89 (dd, 3J
N
ACHTUNGTRENNUNG
2H; Ar-H), 7.76–7.72 (m, 4H; Ar-H), 7.62 (dd, 3J
A
A
ACHTUNGTRENNUNG
Chem. Eur. J. 2013, 19, 14836 – 14851
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
14847

P. V. Murphy et al.
7.43 (m, 4H; Ar-H), 7.35 (t, 3J
(H,H)=7.8 Hz, 2H; Ar-H), 7.03 (d, 3J
3J(H,H)=1.4 Hz, 1H; H-4), 6.08 (dd, 3J
5.96 (dd, J
G
3.2 Hz, 1H; Ar-H), 5.12 (d, 2J
(H,H)=11.7 Hz, 1H; 1ꢂPhCHH), 4.62 (d, 2J
PhCHH), 4.47–4.38 (m, 2H; 1ꢂPhCHH and H-1), 4.34 (d, 2J
11.9 Hz, 1H; 1ꢂPhCHH), 4.12–4.04 (m, 2H; 1ꢂPhCHH and H-4), 3.92
ACHTUNGTRENNUNG
E
R
U
ACHTUNGTRENNUNG
A
R
ACHTUNGTRENNUNG
3
ACHTUNGTRENNUNG
3H; CH3); 13C (125 MHz, CDCl3): d=166.4, 165.5, 165.4, 165.1, 160.2
(each C=O), 133.7, 133.6, 133.4 (each CH), 130.0, 129.8, 129.7 (each CH),
128.8, 128.7 (each C), 128.6 (CH), 128.6(C), 128.4, 128.3 (each CH), 93.6
(C-1), 90.6 (C=NH), 71.2 (C-5), 69.4 (C-4), 67.8 (C-3), 67.3 (C-2),
52.9 ppm (CH3); HRMS calcd for C28H25O10 521.1448, found m/z (%)
521.1446 [M+H]+.
3
(t, J
3), 3.71 (m, 2H; H-6aꢄ and H-6b’), 3.67–3.50 (m, 3H; H-6a and H-6b and
H-2), 3.28 (s, 3H; CH3), 0.99 (s, 9H; C
(CH3)3); 13C NMR (125 MHz,
ACHTUNGTREN(NUGN H,H)=7.2 Hz, 1H; H-5’), 3.81 (m, 3H; 1ꢂPhCHH and H-5 and H-
AHCTUNGTRENNUNG
CDCl3): d=171.2, 165.6, 165.3, 165.1 (each C=O), 138.8, 138.4, 138.1
(each C), 135.5, 135.4 (each CH), 133.3, 133.0, 132.9 (each CH), 132.8,
132.4 (each C), 130.0, 129.9, 129.8, 129.7 (2s), (each CH), 129.6, 129.1
(each C), 128.6, 128.5, 128.2 (2s), 128.1, 127.8 (2s) 127.8, 127.7, 127.6 (2s),
127.5 (2s) (each CH), 101.6 (C-1’), 98.5 (C-1), 78.1 (C-3), 77.4 (C-2), 75.1
(C-4), 73.8 (PhCH2), 73.5 (PhCH2), 73.4 (PhCH2), 73.2 (C-5’), 72.2 (C-3’),
70.3 (C-2’), 69.7 (C-6), 69.1 (C-5), 67.6 (C-4’), 60.8 (C-6), 55.3 (OCH3),
Methyl 6-O-(2,3,4-tri-O-benzoyl-5-S-(methoxycarbonyl)-a-l-arabinopyra-
nosyl)-2,3,4-tri-O-benzoyl-a-d-galactopyranose (39): Regioselective gly-
cosidation of 38[34,35] (150 mg, 0.22 mmol) and 37 (100 mg, 0.22 mmol) as
described above gave the intermediate alcohol (165 mg, 77%) as a color-
less foam; 1H NMR (500 MHz, CDCl3): d=8.02–7.92 (m, 8H; Ar-H),
26.6 (CACHTUNRGTNNEU(G CH3)3), 18.9 ppm (CHCAUTNGTERN(NUNG CH3)3); ESI-HRMS calcd for C71H73O14Si
1177.4770, found m/z (%) 1177.4762 [M+H]+.
7.80 (d, 3J
H), 7.52–7.41 (m, 6H; Ar-H), 7.39–7.32 (m, 6H; Ar-H), 7.26 (dd, 3J-
(H,H)=9.1, 6.5 Hz, 2H; Ar-H), 6.17 (d, 3J
(H,H)=3.3 Hz, 1H; H-4’’),
5.78 (dd, 3J(H,H)=10.4, 7.9 Hz, 1H; H-2’), 5.69 (dd, 3J
(H,H)=10.7,
3.5 Hz, 1H; H-2), 5.62 (ddd, 3J
(H,H)=10.5, 7.3, 3.5 Hz, 2H; H-3 and H-
3’), 5.01 (d, 3J(H,H)=3.5 Hz, 1H; H-1), 4.97 (d, 3J
(H,H)=7.9 Hz, 1H;
H-1’), 4.61 (s, 1H; H-5’), 4.54 (s, 1H; H-4), 4.26 (dd, 2J
(H,H)=10.2 Hz,
3J(H,H)=6.4 Hz, 1H; H-6a), 4.18 (t, 3J
(H,H)=6.3 Hz, 1H; H-5), 4.00
(dd, 2J(H,H)=10.2 Hz, 3J
(H,H)=6.4 Hz, 1H; H-6b), 3.61 (s, 3H; CH3),
3.42
(d, 3J(H,H)=5.0 Hz, 1H; OH), 3.17 ppm (s, 3H; CH3); 13C NMR
ACHTUNGTRENNUNG ACHTUNGTERN(NUGN H,H)=7.5 Hz, 1H; Ar-
(H,H)=7.3 Hz, 2H; Ar-H), 7.56 (t, 3J
Methyl 4-O-(2,3,4-tri-O-benzoyl-5-S-(methoxycarbonyl)-a-l-arabinopyra-
nosyl)-2,3,6-tri-O-benzoyl-a-d-galactopyranoside (44): Acetic acid
(13 mL, 1 equiv) was added to a solution of 43 (263 mg, 0.22 mmol) in
THF (6 mL), and the mixture was cooled to 08C. After addition of
TBAF (1m in THF, 0.25 mL, 0.25 mmol), the mixture was stirred at 08C
for 2 h, then diluted with diethyl ether and washed with brine (ꢂ2). The
aqueous phase was reextracted with diethyl ether, and the combined or-
ganic phases were dried with Na2SO4, filtered, and the solvent was re-
moved under diminished pressure. Flash chromatography furnished the
R
ACHTUNGTRENNUNG
R
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
G
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
N
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
desilylated intermediate (172 mg, 82%) as
(500 MHz, CDCl3): d=8.10 (d, 3J(H,H)=7.3 Hz, 2H; Ar-H), 7.93 (d, 3J-
(H,H)=7.4 Hz, 2H; Ar-H), 7.82 (d, J
3J(H,H)=7.4 Hz, 1H; Ar-H), 7.51 (t, 3J
7.33 (m, 7H; Ar-H), 7.33–7.20 (m, 10H; Ar-H), 7.17 (t, J
2H; Ar-H), 6.97 (dd, 3J(H,H)=6.5, 2.7 Hz, 2H; Ar-H), 5.84 (dd, 3J-
(H,H)=10.3, 8.0 Hz, 1H; H-2’), 5.79 (d, 3J
(H,H)=3.4 Hz, 1H; H-4’),
5.52 (dd, 3J(H,H)=10.3, 3.4 Hz, 1H; H-3’), 5.04 (d, 3J
(H,H)=8.0 Hz,
1H; H-1’), 4.70–4.59 (ABq, 2J
(H,H)=16.8, 11.7 Hz, 2H; PhCH2), 4.58–
4.49 (ABq, 2J(H,H)=15.9, 12.2 Hz, 2H; PhCH2), 4.44 (d, 3J
(H,H)=
3.6 Hz, 1H; H-1), 4.18 (d, J
(H,H)=2.4 Hz, 1H; H-4), 4.05 (dd, 2J
1H; H-6a), 3.95 (dd, 3J(H,H)=7.9, 5.2 Hz, 1H; H-5), 3.89 (d, 2J
11.8 Hz, 1H; 1ꢂPhCH2), 3.75 (m, 2H; H-5 and H-3), 3.72–3.65 (m, 1H;
H-6a’), 3.65–3.54 (m, 2H; H-6b and H-2), 3.45 (dd, 3J
(H,H)=10.6,
a
white foam; 1H NMR
(125 MHz, CDCl3): d=166.8, 166.1, 165.8, 165.6, 165.2, 165.1 (each C=
O), 133.6, 133.4 (ꢂ2), 133.2, 133.1 (each CH), 130.0, 129.8 (ꢂ2), 129.7
(each CH), 129.5, 129.2, 128.8, 128.7 (each C), 128.6, 128.4 (2s), 128.3
(each CH), 101.4 (C-1’’), 97.3 (C-1), 72.6 (C-5’), 71.3 (C-3’), 70.9 (C-2),
69.3 (C-3 and C-2’), 68.9 (C-4’), 68.7 (C-6), 68.5 (C-5), 67.3 (C-4), 55.1
(CH3), 52.9 ppm (CH3); ESI-HRMS calcd for C49H45O17 905.2657, found
m/z (%) 905.2655 [M+H]+. This intermediate (125 mg, 0.132 mmol) was
benzoylated using pyridine (4 mL) and benzoyl chloride (30 mL,
0.263 mmol) as described above to give 39 (118 mg, 90%) as a white
solid after chromatography (petroleum ether/EtOAc 2:1); 1H NMR
(500 MHz, CDCl3): d=8.11–8.05 (m, 2H; Ar-H), 8.05– 8.00(m, 2H; Ar-
H), 7.93 (m, 4H; Ar-H), 7.81–7.78 (m, 2H; Ar-H), 7.76–7.72 (m, 2H; Ar-
H), 7.60 (m, 2H; Ar-H), 7.53–7.30 (m, 12H; Ar-H), 7.29–7.17 (m, 4H;
Ar-H), 6.21–6.12 (m, 1H; H-4’), 5.90 (m, 2H; H-4, H-3), 5.83 (dd, 3J-
AHCTUNGTRENNUNG
3
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
3
AHCTUNGTREGUN(NN H,H)=7.8 Hz,
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
2
3
AHCTUNGTRENNUNG
A
R
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
E
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
5.0 Hz, 1H; H-6b), 3.32–3.27 (m, 1H; OH), 3.26 (s, 3H; CH3); 13C NMR
(125 MHz, CDCl3): d=166.3, 165.6, 165.3 (each C=O), 138.7, 138.4, 137.8
(each C), 133.7, 133.3, 133.0 (each CH), 130.0 (2s), 129.8 (each CH),
129.5, 128.9, 128.8 (each C), 128.7, 128.6, 128.5, 128.3, 128.2, 128.1, 128.0,
127.9 (2 s), 127.8 (3s) (each CH), 102.3 (C-1’), 98.8 (C-1), 77.9 (C-3), 77.1
(C-2), 76.0 (C-4), 74.0 (C-5’), 73.7 (2ꢂPhCH2), 73.5 (PhCH2), 72.2 (C-3’),
70.1 (C-2’), 68.8 (C-4’), 68.3 (C-6), 67.6 (C-5), 61.0 (C-6’), 55.3 ppm
(CH3); ESI-HRMS calcd for C55H54NaO14 961.3411, found m/z (%)
961.3407 [M+Na]+. This intermediate (326 mg, 0.35 mmol) was added to
CH2Cl2 (10 mL) and H2O (5 mL) and treated with TEMPO (10 mg,
0.065 mmol) and BAIB (336 mg, 1.043 mmol) to give the acid. This was
esterified in DMF (10 mL) using NaHCO3 (220 mg, 2.6 mmol) and MeI
(0.055 mL, 0.87 mmol) to give the ester (290 mg, 87%) after chromatog-
A
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
G
ACHTUNGTRENNUNG
G
ACHTUNGTRENNUNG
CH3), 3.10 ppm (s, 3H; CH3); 13C NMR (125 MHz, CDCl3): d=166.3,
166.1, 165.5 (2s) 165.3, 165.2 (2s) (each C=O), 133. (2s), 133.3 (2s), 133.0
(each CH), 130.0, 129.9, 129.8 (2s), 129.7, 129.6 (each CH), 129.3, 129.2
(2s), 128.9, 128.7 (each C), 128.6 (2s), 128.4 (2s), 128.4, 128.3, 128.2 (each
CH), 101.9 (C-1’), 97.0 (C-1), 72.9 (C-5’), 71.2 (C-3’), 70.2 (C-6), 70.0 (C-
4), 69.4 (C-2), 69.2 (C-2’), 69.1 (C-4’), 68.4 (C-5), 68.9 (C-3), 55.0 (CH3),
52.8 ppm (CH3); ESI-HRMS calcd for C56H49O18 1009.2919, found m/z
(%) 1009.2924 [M+H]+.
Methyl 4-O-(6-O-tert-butyldiphenylsilyl-2,3,4-tri-O-benzoyl-b-d-galacto-
pyranosyl)-2,3,6-tri-O-benzyl-a-d-galactopyranose (43): Tf2O (0.080 mL,
0.48 mmol) was added to a stirred solution of the thioglycoside 41[36,37]
(370 mg, 0.44 mmol), benzene sulfonyl pyridine (92 mg, 0.44 mmol),
2,4,6-tri-tert-butylpyrimidine (220 mg, 0.89 mmol), and activated 3 ꢃ pow-
dered sieves in CH2Cl2 (5 mL), at ꢀ608C, under argon. After 5 min, a so-
lution of the glycosyl acceptor 42 (286 mg, 0.60 mmol) in dichlorome-
thane (4 mL) was added. The mixture was allowed to attain room tem-
perature, filtered, washed with satd. aq. NaHCO3, brine, dried (Na2SO4),
and the solvent was then removed under diminished pressure. Chroma-
tography of the residue (petroleum ether/EtOAc, 3:1) gave the title com-
raphy (petroleum ether/EtOAc 2:1) as
(500 MHz, CDCl3): d=8.02 (dd, 3J
(H,H)=8.2, 1.1 Hz, 2H; Ar-H), 7.96
(dd, 3J(H,H)=8.3, 1.1 Hz, 2H; Ar-H), 7.83 (dd, 3J
(H,H)=8.3, 1.2 Hz,
2H; Ar-H), 7.63–7.57 (m, 1H; Ar-H), 7.51–7.16 (m, 21H; Ar-H), 7.01
(dd, 3J(H,H)=6.8, 2.6 Hz, 2H; Ar-H), 6.14 (dd, 3J
(H,H)=3.4, 1.1 Hz,
1H; H-4’), 5.80 (dd, 3J(H,H)=10.4, 7.9 Hz, 1H; H-2’), 5.53 (dd, 3J-
(H,H)=10.4, 3.4 Hz, 1H; H-3’), 5.18 (d, 3J
(H,H)=7.9 Hz, 1H; H-1’),
4.71 (dd, 2J(H,H)=11.8, 8.0 Hz, 2H; PhCH2), 4.64 (dd, 2J
(H,H)=11.8,
4.3 Hz, 2H; PhCH2), 4.50 (d, 3J(H,H)=3.6 Hz, 1H; H-1), 4.43 (d, 3J-
(H,H)=1.2 Hz, 1H; H-5’), 4.26 (d, 3J
(H,H)=2.4 Hz, 1H; H-4), 4.15 (d,
2J(H,H)=11.7 Hz, 1H; PhCHH), 4.01 (dd, 2J(H,H)=9.9 Hz, 3J
(H,H)=
6.0 Hz, 1H; H-6a), 3.96 (t, J
11.7 Hz, 1H; PhCHH), 3.86 (dd, 3J
(dd, 2J(H,H)=9.9 Hz, 3J
a
white foam; 1H NMR
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
1
A
E
ACHTUNGTRENNUNG
pound 43 (466 mg, 90%) as a white foam; H NMR (500 Hz, CDCl3): d=
3
2
8.04 (d, J=7.4 Hz, 2H; Ar-H), 7.91 (d, J=7.5 Hz, 2H; Ar-H), 7.82 (d,
E
ACHTUNGTRENNUNG(H,H)=
J=7.4 Hz, 2H; Ar-H), 7.64 (dd, 3J
(H,H)=13.1, 7.0 Hz, 3H; Ar-H), 7.49
ACHTUNGTRENNUNG
3
(t, J
G
A
ACHTUNGTRENUN(NG H,H)=6.0 Hz, 1H; H-6b), 3.65–3.59 (m, 4H;
15H; Ar-H), 6.95 (d, 3J
N
G
CH3 and H-2), 3.32 ppm (s, 3H; CH3); 13C NMR (125 MHz, CDCl3): d=
166.2, 165.6, 165.2, 165.1 (each C=O), 138.8 (2s), 138.4 (each C), 133.5,
AHCTUNGTRENNUNG
14848
www.chemeurj.org
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 14836 – 14851

Regiospecific Anomerisation
FULL PAPER
133.3, 133.1 (each CH), 130.0, 129.9, 129.8 (each CH), 129.5, 129.1, 128.8
(each C), 128.6 (2s), 128.3 (3s), 128.2, 127.9, 127.7 (3s), 127.6, 127.5, 127.4
(each CH), 101.6 (C-1’), 98.5 (C-1), 78.2 (C-3), 77.4 (C-2), 76.1 (C-4),
73.9 (PhCH2), 73.5 (PhCH2), 73.4 (PhCH2), 72.5 (C-5’), 71.6 (C-3’), 70.0
(C-6), 69.5 (C-2’), 69.3 (C-5), 69.1 (C-4’), 55.3 (CH3), 52.5 ppm (CH3);
ESI-HRMS calcd for C56H54NaO15 989.3360, found m/z (%) 989.3355
[M+Na]+. To this intermediate (155 mg, 0.160 mmol) in MeOH (5 mL),
Pd/C (30 mg) was added and the mixture was stirred under hydrogen for
24 h. The mixture was filtered through Celite and the filtrate concentrat-
ed to dryness. The residue was taken up in pyridine (4 mL) and cooled to
08C and benzoyl chloride (100 mL, 0.80 mmol) was added and the reac-
tion allowed to attain room temperature for 24 h. Work up as described
previously and chromatography (petroleum ether/EtOAc 1:1) gave 44
2,3,4-Tri-O-benzoyl-6-O-(2,3,4-tri-O-benzoyl-5-S-(methoxycarbonyl)-a-d-
xylopyranosyl)-b-d-glucopyranosyl azide (53): [a]D =44.9 (c 1.1, CH2Cl2);
1H NMR (500 MHz, CDCl3): d=8.13–8.02 (m, 2H; Ar-H), 8.00 (dd, 3J-
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
3
(d, JACHTGNUTRENNUNG
A
ACHTUNGTRENNUNG
2
A
ACHTUNGTRENNUNG
13C NMR (126 MHz, CDCl3): d=168.3 (CO2CH3), 165.9, 165.8, 165.7,
165.5, 165.2, 165.0 (6ꢂCOPh), 133.7 (2s), 133.6, 133.5, 133.3, 130.1 (2s),
130.0, 129.9 (2s) (18ꢂAr-CH, overlapping peaks), 129.2, 129.1, 129.0,
128.9 (4ꢂAr-C), 128.7 (2s) (2ꢂAr-CH, Ar-C, overlapping peaks), 128.6
(2s) (4ꢂAr-CH, Ar-C, overlapping peaks), 128.5 (2s), 128.4 (6ꢂAr-CH,
overlapping peaks), 96.4 (C-1’), 88.2 (C-1), 75.5 (C-5), 72.9 (C-3), 71.5
(C-2), 71.3 (C-2’), 70.2 (C-4’) 69.9 (C-3’), 68.9 (C-4), 68.6 (C-5’), 67.0 (C-
6), 52.9 ppm (CO2CH3); IR (film): n˜ =2955, 2924, 2118, 1726, 1451, 1248,
1090, 1067, 1025 cmꢀ1; ESI-HRMS calcd for C55H45O17N3Na 1042.2647,
found m/z (%) 1042.2649 [M+Na]+.
1
(138 mg, 86%) as a white solid; H NMR (500 MHz, CDCl3): d=8.12 (d,
3J
(d, 3J
7.83 (m, 4H; Ar-H), 7.63–7.53 (m, 3H, Ar-H), 7.53–7.42 (m, 6H; Ar-H),
7.39–7.24 (m, 7H; Ar-H), 7.16 (t, 3J
(H,H)=7.8 Hz, 2H; Ar-H), 6.12 (d,
3J
(H,H)=2.5 Hz, 1H; H4’), 5.89–5.82 (m, 2H; H-2ꢄ and H-3), 5.57 (dd, J-
(H,H)=10.5, 2.5 Hz, 1H; H-3’), 5.37 (dd, 3J
(H,H)=10.8, 3.5 Hz, 1H; H-
ACHTUNGTRENNUNG ACHTUNGTRENNUNG
(H,H)=7.2 Hz, 2H; Ar-H), 8.05 (d, 3J
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
3
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
3
3
2), 5.24 (d, J
1’), 4.96 (dd, 2J
(H,H)=12.1 Hz, 3J
G
ACHTUNGTREN(NUGN H,H)=7.9 Hz, 1H; H-
E
ACHTUNGTRENNUNG
E
U
ACHTUNGTRENNUNG
2-O-Acetyl-3-O-(2,3,4-tri-O-benzoyl-5-S-(methoxycarbonyl)-a-d-xylopyr-
anosyl)-4,6-O-(1,1,3,3-tetraisopropyl-1,3-disiloxanediyl)-b-d-glucopyrano-
syl azide (54): [a]D =ꢀ9.7 (c 0.35, CH2Cl2); 1H NMR (500 MHz, CDCl3):
1H; H-4), 4.48–4.39 (m, 2H; H-5 and H-5’), 3.61 (s, 3H; CH3), 3.39 ppm
(s, 3H; CH3); 13C NMR (125 MHz, CDCl3): d=166.2, 166.0, 165.9, 165.6,
165.4, 165.2 (s), (each C=O), 133.6 (2s), 133.4, 133.1, 132.9 (2s), 132.9
(each CH), 130.3 (C), 130.1, 129.8 (2s), 129.8, 129.7 (2s) (each CH),
129.4, 129.3, 129.0, 128.9 (each C), 128.7 (2s, CH), 128.7 (C), 128.4, 128.3,
128.2 (2s) (each CH), 101.0 (C-1), 97.3 (C-1), 74.7 (C-4), 72.7 (C-5), 71.2
(C-3’), 70.6 (C-3), 69.7 (C-2’), 69.4 (C-2), 69.0 (C-4), 68.1 (C-5), 64.5 (C-
6), 55.3 (CH3), 52.7 ppm (CH3). ESI-HRMS calcd for C56H49O18
1009.2919, found m/z (%) 1009.2922 [M+H]+.
d=8.00 (dd, 3J(H,H)=8.2, 1.4 Hz, 2H; Ar-H), 7.95 (dd, 3J
ACTHNUTRGENNUG ACHUTGNTREN(NUNG H,H)=8.3,
1.4 Hz, 2H; Ar-H), 7.90 (dd, 3J
(m, 2H; Ar-H), 7.46–7.36 (m, 5H; Ar-H), 7.31 (t, 3J
Ar-H), 6.19 (aptt, 3J
(H,H)=9.9 Hz, 1H; H-3’), 5.68–5.62 (m, 2H; H-1’,
H-4’, overlapping peaks), 5.32 (dd, J
(d, 3J(H,H)=10.1 Hz, 1H; H-5’), 4.56 (aptt, 3J
4.43 (d, J
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
3
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
3
AHCTUNGTRENNUNG
General procedure for the anomerisation reaction (conditions B; see
Tables 1 and 2): The b-anomer (1 equiv) was added to a flame-dried
round bottomed flask and anhydrous CH2Cl2 (10 mL per g of substrate)
was added. The flask was then cooled on an ice-bath and 2.5 equiv TiCl4
(1m in CH2Cl2) was added dropwise. The flask was then left to stand in
a freezer (ꢀ15 to ꢀ188C) for 48–72 h. The mixture was diluted with
CH2Cl2 and washed with NH4Cl (1.0M, 10 mL). The aqeous layer was ex-
tracted with CH2Cl2 and the combined organic layers were washed with
satd. aq. NaHCO3 and brine. The organic layer was dried over Na2SO4,
filtered through silica gel and the solvent removed to give the products.
lapping peaks), 3.71–3.63 (m, 5H; CO2CH3, H-3, H-4, overlapping
peaks), 3.53–3.46 (m, 1H; H-5) 2.05 (s, 3H; COCH3), 1.22–0.94 (m, 28H;
4ꢂCHACHTNUGRTNEUNG
(CH3)2, overlapping peaks); 13C NMR (126 MHz, CDCl3): d=
168.9 (COCH3), 168.4 (CO2CH3), 165.7 (2s), 165.5 (3ꢂCOPh), 133.6,
133.5, 133.3, 130.0, 129.9 (9ꢂAr-CH, overlapping peaks), 129.2, 129.0,
128.9 (3ꢂAr-C), 128.7, 128.5 (2s) (6ꢂAr-CH, overlapping peaks), 96.6
(C-1’), 87.9 (C-1), 77.9 (C-5), 77.6 (C-4), 72.5 (C-2), 72.4 (C-3), 71.6 (C-
2’), 70.3 (C-4), 69.8 (C-3’), 68.7 (C-5), 65.9 (C-6), 53.0 (CO2CH3), 20.8
(COCH3), 17.4 (4s), 17.3 (2s) (8ꢂCH
12.8, 12.3, 12.2 ppm (4ꢂCH
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
2925, 2867, 2117, 1731, 1452, 1260, 1095, 1067, 1041, 983 cmꢀ1; ESI-
HRMS calcd for C48H61O16N3Si2Na 1014.3488, found m/z (%) 1014.3492
[M+Na]+.
2-O-(2,3,4-Tri-O-benzoyl-5-S-(methoxycarbonyl)-a-d-xylopyranosyl)-3,4-
O-(1,1,3,3-tetraisopropyl-1,3-disiloxanediyl)-6-O-acetyl-b-d-glucopyrano-
syl azide (52): [a]D =48.0 (c 0.35, CH2Cl2); 1H NMR (500 MHz, CDCl3):
d=8.00 (dd, 3J
G
2,4,6-Tri-O-benzoyl-3-O-(2,3,4-tri-O-benzoyl-5-S-(methoxycarbonyl)-a-d-
xylopyranosyl)-b-d-glucopyranosyl azide (55): [a]D =40.2 (c 0.95,
CH2Cl2); 1H NMR (500 MHz, CDCl3): d=8.15–8.10 (m, 2H; Ar-H),
8.08–8.03 (m, 2H; Ar-H), 8.02–7.98 (m, 2H; Ar-H), 7.97–7.94 (m, 2H;
Ar-H), 7.94–7.89 (m, 3H Ar-H), 7.83–7.77 (m, 2H; Ar-H), 7.64–7.60 (m,
7.88 (dd, 3J
ACHTUNGTRENNUNG(H,H)=8.3, 1.5 Hz, 2H; Ar-H), 7.57–7.49 (m, 1H; Ar-H),
7.46–7.37 (m, 5H; Ar-H), 7.30 (t, 3J
3
(aptt, J
G
3
5.65 (aptt, J
A
E
1H; Ar-H), 7.56–7.27 (m, 19H; Ar-H), 6.29 (aptt, 3J
H-3’), 5.88 (aptt, 3J(H,H)=9.7 Hz, 1H; H-3), 5.68 (aptt, 3J
9.8 Hz, 1H; H-4’), 5.59 (aptt, 3J(H,H)=9.8 Hz, 1H; H-4), 5.51 (d, 3J-
ACHTUNGERTN(NUNG H,H)=3.7 Hz, 1H; H-1’), 5.40–5.30 (m, 2H; H-2, H-2’, overlapping
ACHTUNGTRENNUNG
E
G
E
ACHTUNGTRENNUNG
3
G
G
ACHTUNGTRENNUNG
G
E
N
peaks), 4.90 (d, 3J(H,H)=8.8 Hz, 1H; H-1), 4.74 (d, 3J
ACTHNGUTRENNUG CAHTUNGTRENNUNG
N
1H; H-5’), 4.11 (ddd, 3J
G
3
2
E
(H,H)=11.3 Hz, J
E
G
CDCl3): d=170.7 (COCH3), 168.2 (CO2CH3), 165.6, 165.4, 165.3 (3ꢂ
COPh), 133.4 (2s), 133.2, 129.8, 129.7 (9ꢂAr-CH, overlapping
peaks),129.1, 129.0, 128.9 (3ꢂAr-C) 128.5, 128.4, 128.3 (6ꢂAr-CH, over-
lapping peaks), 94.9 (C-1’), 89.7 (C-1), 78.0 (C-3), 76.9 (C-2), 75.7 (C-5),
72.7 (C-4), 71.0 (C-2’), 70.0 (C-4’), 69.0 (C-3’), 68.6 (C-5’), 62.7 (C-6), 52.7
(CO2CH3), 29.7 (COCH3), 20.8, 17.5 (2s), 17.4, 17.3, 17.2 (2s), 17.1 (2s)
ACTHNGUTERNNUG
3J(H,H)=1.7 Hz, 1H; H-6b), 3.60 ppm (s, 3H; CO2CH3); 13C NMR
(126 MHz, CDCl3): d=168.1 (CO2CH3), 165.7 (2s), 165.6, 165.4, 165.0,
164.8 (6ꢂCOPh), 133.7, 133.6, 133.5 (2s), 133.3, 133.2, 130.2, 130.0 (2s),
129.9, 129.8 (2s) (18ꢂAr-CH, overlapping peaks), 129.1, 128.9, 128.8 (2s),
128.6 (5ꢂAr-C), 128.5 (3s) (4ꢂAr-CH, Ar-C, overlapping peaks), 128.4
(2s), 128.3 (2s) (8ꢂAr-CH, overlapping peaks), 96.3 (C-1’), 88.1 (C-1),
75.4 (C-5), 72.8 (C-3), 71.3 (C-3’), 71.2 (C-4’), 70.0 (C-2’), 69.8 (C-2), 68.8
(C-4), 68.4 (C-5’), 66.8 (C-6), 52.8 ppm (CO2CH3); IR (film): n˜ =2957,
2924, 2119, 1724, 1452, 1248, 1090, 1067, 1025 cmꢀ1; ESI-HRMS calcd for
C55H45O17N3Na 1042.2647, found m/z (%) 1042.2653 [M+Na]+.
(8ꢂCHACHTUNGTRENNUNG(CH3)2, overlapping peaks), 12.9, 12.7, 12.2, 11.4 ppm (4ꢂCH-
ACHTUNGTRENNUNG(CH3)2, overlapping peaks); IR (film): n˜ =3072, 2953, 2120, 1727, 1452,
1248, 1091, 1067, 1026 cmꢀ1; ESI-HRMS calcd for C48H61O16N3Si2Na
1014.3488, found m/z (%) 1014.3494 [M+Na]+.
Chem. Eur. J. 2013, 19, 14836 – 14851
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
14849

P. V. Murphy et al.
2,3-O-(1,1,3,3-Tetraisopropyl-1,3-disiloxanediyl)-4-O-(2,3,4-tri-O-benzoyl-
5-S-(methoxycarbonyl)-a-d-xylopyranosyl)-6-O-acetyl-b-d-glucopyrano-
7.79 (m, 2H; Ar-H), 7.64–7.23 (m, 18H; Ar-H), 6.27 (dd, 3J
1.9 Hz, 1H; H-4’), 6.18 (dd, 3J
(H,H)=11.0, 3.4 Hz, 1H; H-3’), 5.89–5.80
ACHTUNGTRENUN(NG H,H)=3.4,
AHCTUNGTRENNUNG
3
3
1
(m, 2H; H-2ꢄ and H-2), 5.63 (d, J
(H,H)=11.0, 2.6 Hz, 1H; H-3), 5.30 (d, J
(d, 3J(H,H)=3.6 Hz, 1H; H-1), 4.67 (d, 3J
(dd, 2J(H,H)=10.3 Hz, 3J
(H,H)=5.9 Hz, 1H; H-6a), 4.38–4.32 (m, 1H;
H-5), 4.28 (dd, 2J(H,H)=10.3 Hz, 3J
(H,H)=8.3 Hz, 1H; H-6b), 3.45 (s,
ACHTUNGTRNE(NUNG H,H)=3.6 Hz, 1H; H-1’), 5.59 (dd, J-
syl azide (56): [a]D = +29.0 (c 0.2, CH2Cl2); H NMR (500 MHz, CDCl3):
3
d=8.05 (dd, 3J
ACHTUNGTRENNUNG
N
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
3H; OCH3), 3.08 ppm (s, 3H; COOCH3); 13C NMR (125 MHz, CDCl3):
d=166.6, 166.3, 166.0, 165.8, 165.6, 165.5, 165.0 (each C=O), 133.5, 133.4,
133.3, 133.2 (2s), 129.8 (2s), 129.7 (2s) (each CH), 129.3 (2s) 129.1, 129.0,
128.9, 128.6 (each C), 128.5 (2s) 128.4 (2s), 128.3, 128.2 (each CH), 99.5
(C-1’), 97.7 (C-1), 77.1 (C-4), 71.0 (C-3), 70.2 (C-4’), 70.0 (C-5’), 68.5 (C-
2ꢄ and C-2), 67.5 (C-3’), 67.2 (C-5), 60.8 (C-6), 55.7 (CH3), 52.1 ppm
(CH3). ESI-HRMS calcd for C56H48NaO18 1031.2738, found m/z (%)
1031.2742 [M+Na]+.
G
ACHTUNGTRENNUNG
2
3
ACHTUNGTRENNUNG(H,H)=12.2 Hz, JACTHUNGTRENNNUG
G
T
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
(126 MHz, CDCl3): d=170.7 (COCH3), 168.4 (COCH3), 165.4, 165.2 (3ꢂ
COPh, overlapping peaks), 133.7, 133.4, 130.1, 130.0, 129.8 (9ꢂAr-CH,
overlapping peaks), 199.3 128.8, 128.6 (3ꢂAr-C) 128.4, 128.4, 128.3 (6ꢂ
Ar-CH, overlapping peaks), 94.6 (C-1’), 90.5 (C-1), 80.3 (C-3), 76.7 (C-2),
74.4 (C-5), 74.2 (C-4) 72.3 (C-5’), 68.6 (H-3’), 68.2 (H-4’), 67.4 (H-2’) 63.0
(C-6), 52.6 (CO2CH3), 20.8 (COCH3), 17.3 (2s), 17.2 (2s), 17.1, 16.9 (8ꢂ
Supporting information: Additional experimental prodedures and NMR
spectra can be found in the Supporting Information.
CH
ACHTUNGTRENNUNG(CH3)2, overlapping peaks), 12.9, 12.7, 12.1, 12.0 ppm (4ꢂCHACHTUGNTRENN(UNG CH3)2,
overlapping peaks); IR (film): n˜ =2927, 2868, 2118, 1729, 1452, 1246,
Acknowledgements
1091, 1068, 1026, 988 cmꢀ1
; ESI-HRMS calcd for C48H61O16N3Si2Na
1014.3488, found m/z (%) 1014.3467 [M+Na]+.
Material presented herein was supported by Science Foundation Ireland
(Grant No. 12/IA/1398) and the Irish Research Council through an En-
terprise Partnership funded by Roche Ireland, Ltd. (M.F.).
2,3,6-Tri-O-benzoyl-4-O-(2,3,4-tri-O-benzoyl-5-S-(methoxycarbonyl)-a-d-
xylopyranosyl)-b-d-glucopyranosyl azide (57): [a]D = +65.3 (c 0.15,
CH2Cl2); 1H NMR (500 MHz, CDCl3): d=8.07–8.02 (m, 2H; Ar-H),
8.01–7.98 (m, 2H; Ar-H), 7.97–7.94 (m, 2H; Ar-H), 7.91 (ddd, 3J
ACHTUNGTRENNUNG
[1] For recent reviews on O-glycoside synthesis, see: a) L. K. Mydock,
A. V. Demchenko, Org. Biomol. Chem. 2010, 8, 497–510; b) X.
Zhu, R. R. Schmidt, Angew. Chem. 2009, 121, 1932–1967; Angew.
Chem. Int. Ed. 2009, 48, 1900–1934.
[2] a) D. Crich, J. Org. Chem. 2011, 76, 9193–9209; b) P. H. Seeberger,
D. B. Werz, Nature 2007, 446, 1046–1051; c) B. Lepenies, J. Yin,
P. H. Seeberger, Curr. Opin. Chem. Biol. 2010, 14, 404–411; d) P. H.
Seeberger, Chem. Soc. Rev. 2008, 37, 19–28; e) C. H. Hsu, S. H.
Hung, C. Y. Wu, C. H. Wong, Angew. Chem. 2011, 123, 12076–
12129; Angew. Chem. Int. Ed. 2011, 50, 11872–11923.
[3] a) M. Tosin, P. V. Murphy, Org Lett 2002, 4, 3675–3678; b) M.
Polꢅkovꢅ, N. Pitt, M. Tosin, P. V. Murphy, Angew. Chem. 2004, 116,
2572–2575; Angew. Chem. Int. Ed. 2004, 43, 2518–2521; c) C. Oꢄ
Brien, M. Polꢅkovꢅ, N. Pitt, M. Tosin, P. V. Murphy, Chem. Eur. J.
2007, 13, 902–909; d) L. Cronin, M. Tosin, H. Mꢆller-Bunz, P. V.
Murphy, Carbohydr. Res. 2007, 342 111–118; e) M. Tosin, C. Oꢄ
Brien, G. M. Fitzpatrick, H. Mꢆller-Bunz, W. K. Glass, P. V. Murphy,
J. Org. Chem. 2005, 70, 4096–4106; f) M. Tosin P. V. Murphy, J. Org.
Chem. 2005, 70, 4107–4117; g) T. Velasco-Torrijos, P. V. Murphy,
Org. Lett. 2004, 6, 3961–3964.
[4] R. U. Lemieux, in Molecular Rearrangements (Ed.: P. De Mayo),
Wiley Interscience, New York, 1964, pp. 709–769; b) S. Koto, in
Glycoscience: Chemistry and Chemical Biology (Eds: B. Fraser-
Reid, K. Tatsuta, J. Thiem), Springer, Heidelberg, 2001, pp. 785–
876.
[5] W. Pilgrim, P. V. Murphy, J. Org. Chem. 2010, 75, 6747–6755.
[6] Z. Gyçrgydeꢅk, J. Thiem, Carbohydr. Res. 1995, 268, 85–92.
[7] C. Vogel, W. Steffan, H. Boye, H. Kristen, V. I. Betaneli, A. Y. Ott,
N. K. Kotetchkov, Carbohydr. Res. 1992, 237, 131–144.
[8] a) D. Comegna, F. De Riccardis, Org. Lett. 2009, 11, 3898–3901;
b) L. Ying, J. Gervay-Hague, Carbohydr. Res. 2003, 338, 835–841.
[9] D. J. Lee, K. Mandal, P. W. R. Harris, M. A. Brimble, S. B. H. Kent,
Org. Lett. 2009, 11, 5270–5273.
[10] L. G. Weaver, Y. Singh, J. T. Blanchfield, P. L. Burn, Carbohydr. Res.
2013, 371, 68–76.
[11] a) P. V. Murphy, H. Bradley, M. Tosin, N. Pitt, G. M. Fitzpatrick,
W. K. Glass, J. Org. Chem. 2003, 68, 5693–5704; b) A. Bianchi, A.
Bernardi, J. Org. Chem. 2006, 71, 4565–4577.
G
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
3
G
ACHTUNGTRNE(NUNG H,H)=3.7 Hz, 1H; H-1’), 5.38–5.32
3
AHCTUNGTRENNUNG
G
ACHTUNGTRENNUNG
N
ACHTUNGTRENNUNG
G
ACHTUNGTRENNUNG
(s, 3H; CO2CH3); 13C NMR (126 MHz, CDCl3): d=168.1 (CO2CH3),
165.7 (2s), 165.6, 165.4, 165.0, 164.8 (6ꢂCOPh), 133.6, 133.5 (2s), 133.3,
133.2, 130.0, 129.9 (2s), 129.8 (2s) (18ꢂAr-CH, overlapping peaks), 129.1,
128.9, 128.8 (2s), 128.6 (5ꢂAr-C), 128.5 (2s) (2ꢂAr-CH, Ar-C, overlap-
ping peaks), 128.4(2s), 128.3 (2s) (10ꢂAr-CH, overlapping peaks), 96.3
(C-1’), 88.1 (C-1), 75.4 (C-5), 72.8 (C-3), 71.3 (C-2), 71.2 (C-2’), 70.0
(C4’), 69.8 (C-3’), 68.8 (C-4), 68.4 (C-5’), 66.8 (C-6), 52.8 ppm (CO2CH3);
IR (film): n˜ =2952, 2119, 1725, 1452, 1247, 1091, 1067, 1026, 704 cmꢀ1
ESI-HRMS calcd for C55H45O17N3Na 1042.2647, found m/z (%)
1042.2665 [M+Na]+.
;
Methyl 6-O-(2,3,4-tri-O-benzoyl-5-S-(methoxycarbonyl)-b-l-arabinopyra-
nosyl)-2,3,4-tri-O-benzoyl-a-d-galactopyranose (58): 1H NMR (500 MHz,
CDCl3): d=8.08–7.93 (m, 8H; Ar-H), 7.83–7.78 (m, 2H; Ar-H), 7.76–
7.73 (m, 2H; Ar-H), 7.64–7.56 (m, 2H; Ar-H), 7.55–7.32 (m, 12H; Ar-
H), 7.24 (m, 4H; Ar-H), 6.23 (dd, 3J
5.93 (m, 2H; H-3ꢄ and H-3), 5.87 (d, 3J
(dd, 3J(H,H)=10.7, 3.5 Hz, 1H; H-2), 5.66 (dd, 3J
1H; H-2’), 5.48 (d, J
1H; H-1), 5.08 (d, 3J
3.6 Hz, 1H; H-5), 4.00 (dd, 2J
6a), 3.77 (dd, 2J(H,H)=10.5 Hz, 3J
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
G
ACHTUNGTRENNUNG
3
3
A
ACHTUNGTRENNUNG
E
ACHTUNGTRENNUNG
E
ACHTUNGTRENNUNG
G
ACHTUNGTRENNUNG
3H; CH3), 3.54 ppm (s, 3H; CH3); 13C NMR (125 MHz, CDCl3): d=
167.3, 166.1, 165.8, 165.5 (2s), 165.4, 165.2 (each C=O), 133.6, 133.5,
133.4, 133.2, 133.1 (each CH), 129.9 (3s), 129.8, 129.7, 129.6 (each CH),
129.2, 129.1, 129.0 (4s) (each C), 128.6 (2s), 128.4, 128.3, 128.2 (each
CH), 97.6 (C-1), 96.9 (C-1’), 70.0 (C-4), 69.6 (C-4), 69.4 (C-2’), 69.2 (C-
5’), 68.3 (C-3’), 68.3 (C2), 68.0 (C-5), 67.9 (C-3’), 67.7 (C-6), 55.7 (CH3),
52.8 ppm (CH3); ESI-HRMS calcd for C56H48NaO18 1031.2738, found m/z
(%) 1031.2745 [M+Na]+.
Methyl 4-O-(2,3,4-tri-O-benzoyl-5-S-(methoxycarbonyl)-b-l-arabinopyra-
nosyl)-2,3,6-tri-O-benzoyl-a-d-galactopyranose (59): 1H NMR (500 MHz,
CDCl3): d=8.06–8.03 (m, 2H; Ar-H), 7.97–7.90 (m, 8H; Ar-H), 7.83–
[12] C. A. A. Van Boeckel, J. H. Van Boom, Tetrahedron 1985, 41, 4567–
4575.
[13] L. Heng, J. Ning, F. Kong, J. Carbohydr. Chem. 2001, 20, 285–296.
14850
www.chemeurj.org
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 14836 – 14851

Regiospecific Anomerisation
FULL PAPER
[14] Y. A. Lin, J. M. Chalker, B. G. Davis, J. Am. Chem. Soc. 2010, 132,
16805–16811.
[15] J. G. Allen, B. Fraser-Reid, J. Am. Chem. Soc. 1999, 121, 468–469.
[16] K. Ishihara, H. Kurihara, H. Yamamoto, J. Org. Chem. 1993, 58,
3791–3793.
[17] E. van Dijkum, R. Danac, D. J. Hughes, R. Wood, A. Rees, B. L.
Wilkinson, A. J. Fairbanks, Org. Biomol. Chem. 2009, 7, 1097–1105.
[18] a) H. Satoh, S. Manabe, Y. Ito, H. P. Luethi, T. Laino, J. Hutter, J.
Am. Chem. Soc. 2011, 133, 5610–5619.
[19] S. Koto, N. Morishima, R. Kawahara, K. Isikawa, S. Zen, Bull.
Chem. Soc. Jpn. 1982, 55, 1092–1096.
[20] Y. Wang, H. S. Cheon, Y. Kishi, Chem. Asian J. 2008, 3, 319–326.
[21] M. Heuckendorff, C. M. Pedersen, M. Bols, Chem. Eur. J. 2010, 16,
13982–13994.
[22] There is an example in which a catalytic carboxylic acid led to the
inter- and intramolecular promotion of anomerisation in the prepa-
[28] a) F. Pꢀrez-Balderas, M. Ortega-MuÇoz, J. Morales-Sanfrutos, F.
Hernꢅndez-Mateo, F. G. Calvo-Flores, J. A. Calvo-Asꢈn, J. Isac-
Garcꢈa, F. Santoyo-Gonzꢅlez, Org. Lett. 2003, 5, 1951–1954; b) F.
Morvan, A. Meyer, A. Jochum, C. Sabin, Y. Chevolot, A. Imberty,
J. P. Praly, J. J. Vasseur, E. Souteyrand, S. Vidal, Bioconjugate Chem.
2007, 18, 1637–1643; c) S. Andrꢀ, T. Velasco-Torrijos, R. Leyden, S.
Gouin, M. Tosin, P. V. Murphy, H.-J. Gabius, Org. Biomol. Chem.
2009, 7, 4715–4725; d) V. Aragao-Leoneti, V. L. Campo, S. A.
Gomes, R. A. Field, I. Carvalho, Tetrahedron 2010, 66, 9475–9492;
e) V. L. Campo, I. Carvalho, C. H. T. P. Da Silva, S. Schenkman, L.
Hill, S. A. Nepogodiev, R. A. Field, Chem. Sci. 2010, 1, 507–514;
f) A. Papadopolos, T. C. Shiao, R. Roy, Mol. Pharm. 2012, 9, 394–
403.
[29] C. J. Cappiciotti, J. F. Trant, M. Leclꢇre, R. N. Ben, Bioconjugate
Chem. 2011, 22, 605.
[30] a) L. Szilꢉgyi, Z. Gyçrgydeꢉk, Carbohydr. Res. 1985, 143, 21–42;
b) Z. Gyçrgydeꢉk, J. Thiem, Carbohydr. Res. 1995, 268, 85–92; c) L.
Szilꢉgyi, Z. Gyçrgydeꢉk, Liebigs Ann. Chem. 1987, 235–241.
[31] C. Vogel, B. Liebelt, W. Steffan, H. Kristen, J. Carbohydr. Chem.
1992, 11, 287–303.
[32] S. Saito, S. Sumita, K. Ichinose, Y. Kanda, Chem. Pharm. Bull. 1993,
41, 90–96.
[33] P. Kovac, C. P. J. Glaudemans, W. Guo, T. C. Wong, Carbohydr. Res.
1985, 140, 299–311.
[34] N. Tanaka, I. Ogawa, S. Yoshigase, J. Nokami, Carbohydr. Res. 2008,
343, 2675–2679.
[35] K. Yamamoto, Y. Sato, A. Ishimori, K. Miyairi, T. Okuno, N.
Nemoto, H. Shimizu, S. Kidokoro, M. Hashimoto, Biosci. Biotech-
nol. Biochem. 2008, 72, 2039–2048.
[36] Z. Wang, L. Y. Zhou, K. El-Boubbou, K. X. S. Ye, X. F. Huang, J.
Org. Chem. 2007, 72, 6409–6420.
[37] S. Q. Yan, N. Ding, W. Zhang, P. Wang, Y. X. Li, M. Li, Carbohydr.
Res. 2012, 354, 6–20.
ration of an acetylated isopropyl glycoside: R. U. Lemieux,
O
Hindsgaul, Carbohydr. Res. 1980, 82, 195.
[23] a) C. OꢄReilly, P. V. Murphy, Org. Lett. 2011, 13, 5168–5171; b) W.
Pilgrim, P. V. Murphy, Org. Lett. 2009, 11, 939–942; c) S. Deng, J.
Mattner, Z. Zang, L. Bai, L. Teyton, A. Bendelac, P. B. Savage, Org.
Biomol. Chem. 2011, 9, 7659–7663.
[24] S. A. Nepogodiev, R. A. Field, Iben Damager, Annual Plant Reviews
2011, 41, 65–92.
[25] a) D. Giguꢇre, S. Andrꢀ, M. A. Bonin, M. A. Bellefleur, P. C. Pro-
vencal, B. Pucci, R. Roy, H. J. Gabius, Bioorg. Med. Chem. 2011, 19,
3280; b) S. Andrꢀ, D. V. Jarikote, D. Yan, L. Vincenz, G.-N. Wang,
H. Kaltner, P. V. Murphy, H.-J. Gabius, Bioorg. Med. Chem. Lett.
2012, 22, 313–318.
[26] A. E. Christina, L. J. van den Bos, H. S. Overkleeft, G. A. van der
Marel, J. D. C. Codee, J. Org. Chem. 2011, 76, 1692–1706.
[27] a) H. C. Kolb, M. G. Finn, K. B. Sharpless, Angew. Chem. 2001, 113,
2056–2075; Angew. Chem. Int. Ed. 2001, 40, 2004–2021; b) M.
Meldal, C. W. Tornoe, Chem. Rev. 2008, 108, 2952–3015.
Received: July 21, 2013
Published online: September 20, 2013
Chem. Eur. J. 2013, 19, 14836 – 14851
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
14851