Dichloro-cyanoacetimidates as glycosyl donors

Article abstract of DOI:10.1080/07328300701410650

Transformation of 1-O-unprotected glucose and galactose derivatives (1a-d) into O-glycosyl dichloro-cyanoacetimidates (2a-d) was performed with dichloro-cyanoacetonitrile in the presence of DBU as base. Reaction with different acceptors (3a-d) under TMSOT

Full text of DOI:10.1080/07328300701410650

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Dichloro‐cyanoacetimidates as Glycosyl
Donors
Uwe Schmelzer a , Zhaojun Zhang a & Prof. Dr. Richard R. Schmidt a
a Fachbereich Chemie, Universität Konstanz , Konstanz, Germany
Published online: 21 Jun 2007.
To cite this article: Uwe Schmelzer , Zhaojun Zhang & Prof. Dr. Richard R. Schmidt (2007)
Dichloro‐cyanoacetimidates as Glycosyl Donors , Journal of Carbohydrate Chemistry, 26:4, 223-238, DOI:
10.1080/07328300701410650
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Journal of Carbohydrate Chemistry, 26:223–238, 2007
Copyright # Taylor & Francis Group, LLC
ISSN: 0732-8303 print 1532-2327 online
DOI: 10.1080/07328300701410650
Dichloro-cyanoacetimidates
as Glycosyl Donors
Uwe Schmelzer, Zhaojun Zhang, and Richard R. Schmidt
¨
Fachbereich Chemie, Universitat Konstanz, Konstanz, Germany
Transformation of 1-O-unprotected glucose and galactose derivatives (1a–d) into O-
glycosyl dichloro-cyanoacetimidates (2a–d) was performed with dichloro-cyanoacetoni-
trile in the presence of DBU as base. Reaction with different acceptors (3a–d) under
TMSOTf catalysis afforded glycosides 4 in high yields. Competition experiments with
O-glucopyranosyl trichloroacetimidate 10a, bearing a 4-tert-butylbenzyl group at 6-O,
and O-glucopyranosyl dichloro-cyanoacetimidate 10b, bearing a 4-methylbenzyl group
at 6-O, displayed similar reactivities for these two types of glycosyl donors.
Keywords Glycosyl donors, Glycosidation, Catalysis, Leaving group, Dichloromalo-
nitrile, Imidates
INTRODUCTION
O-Glycosyl trichloroacetimidates have become popular because they are
powerful glycosyl donors.[1–3] These donors can be readily obtained by base cat-
alyzed addition of the anomeric hydroxy group to the nitrile group of trichlor-
oacetonitrile. This addition is strongly supported by the electron-withdrawing
trichloromethyl group. Once prepared, these glycosyl donors can be generally
activated by catalytic amounts of (Lewis) acid, conditions that are orthogonal
to their preparation. This way, they react with various nucleophiles to
provide various types of glycosides generally in high yields and high
anomeric stereocontrol.
This glycosidation principle consists of[1] generation of powerful glycosyl
donors by catalyzed reversible addition of the anomeric hydroxy group to the
activating group and[2] activation of this glycosyl donor by a promoter in
Received November 22, 2006; accepted March 23, 2007.
This manuscript has not been published elsewhere and has not been submitted simul-
taneously for publication elsewhere.
Address correspondence to Prof. Dr. Richard R. Schmidt, Fachbereich Chemie, Univer-
¨
sitat Konstanz, Fach M 725, D-78457, Konstanz, Germany. E-mail: richard.schmidt@
uni-konstanz.de
223

U. Schmelzer et al.
224
catalytic amounts (i.e., an agent that is not consumed during the reaction
course). Particularly in large-scale preparations, such methods are generally
superior to methods that require replacement of the anomeric oxygen by
other elements and activation of the glycosyl donor by equimolar amounts
(often even big excess is employed) of a reaction promoter.[3,4] However, for
various reasons, the last methods are still quite popular. For instance, thiogly-
cosides can be generally stored at rt and they tolerate various protecting group
manipulations. We initiated further investigations to provide efficient glycosyl
donors, which follow the principle of O-glycosyl trichloroacetimidate formation
and activation. Previously trifluoroacetonitrile,[5] ketenimines,[5,6] imide
halides having electron-withdrawing carbon substituents,[5,7–10] and their
heterocyclic equivalents[7,11–14] have been investigated. The last two systems
have the disadvantage of furnishing equimolar amounts of salt on glycosyl
donor generation. Additionally, glycosyl donor generation is not reversible;
therefore, a/b-stereocontrol is much more difficult or impossible. Hence, sur-
passing the properties of O-glycosyl trichloroacetimidates is an interesting
task.
We reasoned that replacement of one chlorine atom in trichloroacetonitrile
by a cyano group, that is, using dichloromalonitrile (Sch. 1) as activating agent,
may lead to increased glycosyl donor properties because the negative inductive
effect of the cyano group is bigger than that of the chlorine atom. However, the
influence of the different inductive effects could be modified by the different
size, leading to different conformational preferences of the derived O-glycosyl
dichloro-cyanoacetimidates, or by other effects.
RESULTS AND DISCUSSION
The investigation of the dichloro-cyanoacetimidate leaving group was based on
readily available anomeric O-unprotected glucose and galactose derivatives
1a–d[15–17] (Sch. 1). Reaction with dichloromalonitrile under catalysis with
DBU as base for O-glycosyl trichloroacetimidate formation gave O-gluco- and
Scheme 1: Transformation of 1a–d into O-glycosyl dichloro-cyanoacetimidates 2a–d.

Dichloro-cyanoacetimidates as Glycosyl Donors
225
Figure 1: X-ray structure of 2b.
O-galactopyranosyl dichloro-cyanoacetimidates 2a–d in excellent yields. Only
the a-anomers could be isolated in pure form under these conditions. From
compound 2b crystals could be obtained, which were subjected to X-ray
analysis (Fig. 1).[18] Interestingly, the smaller cyano group was below the
sugar residue, thus exhibiting that the size of the chlorine atom may lead in
O-glycosyl trichloroacetimidates to different conformational preferences.
Reaction of O-acetyl-protected O-glycosyl dichloro-cyanoacetimidates 2a,b
with readily available acceptors 3a–c[19–22] (Sch. 2) led under TMSOTf cataly-
sis to high yields of glycosides 4aa,[23] 4ba,[23] 4bb, and 4bc,[24] respectively
(Sch. 3 and Table 1: entries 1–4). Due to anchimeric assistance, only the
b-linked products were obtained. Investigations with the O-benzyl-protected
glycosyl donors 2c,d and 3a–d as acceptors were also carried out under the
same conditions; this led to glycoside bond formation in very good yields,
even for low reactive acceptor 3d (Table 1, entries 5–11: products 4cc,[25]
4cd,[26,27] 4da, 4db, 4dc,[28] 4dd[29]). Compared with results obtained for O-
glycosyl trichloroacetimidates with typical acceptors, as, for example, 3b and
3c, a higher tendency for a-product formation was observed even at –408C.[2]
To obtain further information on the reactivity of O-glycosyl
dichloro-cyanoacetimidates, competition experiments with an O-glycosyl
Scheme 2: Acceptors 3a–d for the glycosylation reactions.

U. Schmelzer et al.
226
Scheme 3: Glycosylation products of donors 2a–d with acceptors 3a–d.
trichloroacetimidate were carried out. To this end, 6-O-(4-tert-butylbenzyl)-
and 6-O-(4-methylbenzyl)-protected glucose derivatives 9a,b were prepared
(Sch. 4). Readily available glucose derivative 5[30] was silylated with thexyldi-
methylsilyl (TDS) chloride in the presence of imidazole to furnish exclusively
Table 1: Glycosylation Results of acceptors 3a–d with donors 2a–d.
Reaction Conditionsa
Yield
[%]
a/b-
Ratio
Entry Donor Acceptor
Temp.
TMSOTf (eq) Product
1
2
3
4
5
6
7
8
9
2a
2b
2b
2b
2d
2d
2d
2c
2c
2d
2d
3a
3a
3b
3c
3a
3b
3c
3c
3d
3d
3d
rt
rt
08C
0.05
0.025
0.025
0.1
0.02
0.03
0.07
0.05
0.02
0.05
0.05
4aa
4ba
4bb
4bc
4da
4db
4dc
4cc
4cd
4dd
4dd
71
65
82
84
80
89
73
95
90
83
57
b
b
b
b
b
08C
2408C
2408C
2408C
2408C
2408C
2408C
rt
2:1
a
1:4
1:2
1:3
10:1
10
11
aSolvent: CH2Cl2/Hexane, 1:1.

Dichloro-cyanoacetimidates as Glycosyl Donors
227
Scheme 4: Synthesis of glycosyl donors 10a,b. Reagents and conditions: a) TDS-Cl, imidazole,
DMF, rt (97%); b) NaOMe, MeOH, rt (91%); c) TB-Br, NaH, DMF (95%); d) MB-Br, NaH, DMF (97%);
e) TBAF, HOAc, THF (9a: qu, 9b: 92%); f) CCl3CN, DBU, CH2Cl2 (10a: 92%); g) Cl2C(CN)2, DBU,
CH2Cl2, rt (10b: 90%).
b-glycoside 6. Methanolysis of the 6-O-acetyl group ( ! 7) and then alkylation
with 4-tert-butylbenzyl (TB) bromide and 4-methylbenzyl (MB) bromide with
NaH in DMF afforded 6-O-protected compounds 8a and 8b, respectively. 1-O-
Desilylation with tetrabutylammonium fluoride (TBAF) in the presence of
HOAc in THF gave the desired compounds 9a,b. Reaction of 9a with trichlor-
oacetonitrile and of 9b with dichloromalonitrile under standard conditions for
imidate formation with electron-poor nitriles (i.e., catalysis with DBU as base)
furnished O-glycosyl imidates 10a and 10b, respectively.
The 4-tert-butylbenzyl group in 10a and the methyl group in 10b are
quite distant from the anomeric center; therefore, they should have

U. Schmelzer et al.
228
Scheme 5: Competition experiments with donors 10a,b and acceptor 11.
practically no influence on the glycosylation result with 6-O-unportected
methyl glucopyranoside 11[31] as acceptor. However, the 12a/12b product
ratios can be readily derived from the well-separated 1H NMR signals of
the tert-butyl and the methyl group (Sch. 5). Reaction of one equivalent
each of 10a and 10b with subequivalent amounts of 11 (0.4, 1.0, 1.2 equiva-
lents) under standard glycosylation conditions afforded in all cases a slight
excess of disaccharide 12aa,b over 12ba,b in high yield (95%;
12a:12bꢀ6:5; a:bꢀ1:4), thus exhibiting that imidates 10a and 10b possess
similar reactivity. The difference in basicity of the imino group in 10a and
10b, due to the different electro-negativities of the chlorine atom and the
cyano group, could lead to preferred catalyst attack and thus activation of
10a and this way explain the experimental finding. It remains to be seen
whether the lower steric demand of the dichloro-cyanomethyl group over
the trichloromethyl group has advantages in sterically more demanding O-
glycosyl imidate formations.
In conclusion, dichloromalonitrile is a suitable reagent for the base-cata-
lyzed generation of O-glycosyl dichloro-cyanoacetimidates. These compounds
exhibit glycosyl donor properties closely related to those of O-glycosyl
trichloroacetimidates.
EXPERIMENTAL
General Methods
Solvents were purified according to the standard procedures, boiling range
of petroleum ether 35–658C. For flash chromatography, silica gel (J. T. Baker,
particle size 40 mm) was employed. Thin-layer chromatography (TLC) was
carried out using layer plastic foils coated with silica gel 60 F254 (Merck,
layer thickness 0.2 mm). Melting points are reported uncorrected. Optical
rotations were measured using a Perkin-Elmer 241 MC polarimeter 1-dm
cell at 208C. NMR spectra were recorded using Bruker AC 250 Cryospec or
Bruker Avanca-DRX 600 spectrometers with teramethylsilane (TMS) or

Dichloro-cyanoacetimidates as Glycosyl Donors
229
residual H-signal in deuterated solvent as internal standard. MALDI-mass
spectra were recorded on a Kratos Kompact Maldi 2, and 2,5-dihydroxy-
benzoic acid (DHB) or 6-aza-2-thiothymine (ATT) was used as the matrix.
FAB mass spectra were measured on a Finnigan MAT 312/AMD 5000
spectrometer.
O-(2,3,4,6-Tetra-O-acetyl-a-D-glucopyranosyl) Dichloro-cyanoacetimi-
date (2a). To a solution of dichloromalonitrile (0.89 mL, 8.60 mmol) and
three drops of DBU in 3 mL of dichloromethane, a solution of compound 1a
in 7 mL of dichloromethane was added dropwise. After 30 min the reaction
mixture was worked up and purified as described for compound 2b, which furn-
ished 2a (0.95 g, 68%) as colorless foam. The corresponding b-compound (12%)
1
could not be obtained in pure form. TLC (toluene/acetone 4:1): Rf ¼ 0.44. H
NMR (250 MHz, CDCl3): d 8.83 (s, 1H, NH), 6.59 (d, J1,2 ¼ 3.7 Hz, 1H, 1-H),
5.55 (d, J3,2 ¼ 9.8 Hz, 1H, 3-H), 5.19 (t, Jt ¼ 9.8 Hz, 1H, 4-H), 5.15 (dd,
J2,1 ¼ 3.7, J2,3 ¼ 9.8 Hz, 1H, 2-H), 4.32–4.11 (m, 3H, 5-H, 2 6-H), 2.09, 2.06,
2.04, 2.03 (4 s, 12H, 4 OAc). C17H20Cl2N2O10 (483.3). Calcd.: C, 42.25; H,
4.17; N, 5.80. Found: C, 42.26; H, 4.20; N, 5.72.
O-(2,3,4,6-Tetra-O-acetyl-a-D-galactopyranosyl) Dichloro-cyanoaceti-
midate (2b). To a solution of dichloromalonitrile (888 mL, 8.60 mmol) and
three drops of DBU in 3 mL of dichloromethane, a mixture of 2,3,4,6-tetra-O-
acetyl-D-galactopyranose in 7 mL of dichloromethane was slowly added
dropwise. After 30 min stirring at rt the solvent was evaporated in vacuo. Puri-
fication by flash chromatography (toluene/acetone 8 : 1) furnished 2b as an oily
residue, which after recrystallization (petroleum ether/diethyl ether) furn-
ished colorless crystals (1.21 g, 87%). m.p.: 1138C. TLC (toluene/acetone
4 : 1): Rf ¼ 0.41. [a]D ¼ þ106.2 (c 2.0, CHCl3). 1H NMR (250 MHz, CDCl3):
(¼8.76 (bs, 1H, NH), 6.58 (d, J1,2 ¼ 2.6 Hz, 1H, 1-H), 5.54 (m, 1H, 4-H),
5.40–5.30 (m, 2H, 2-H, 3-H), 4.38 (t, Jt ¼ 6.8 Hz, 1H, 5-H), 4.18–3.98 (m, 2H,
2 6-H), 2.14, 2.01, 2.00, 1.98 (4 s, 12H, 4 OAc). C17H20Cl2N2O10 (483.3).
Calcd.: C, 42.25; H, 4.17; N, 5.80. Found: C, 42.30; H, 4.21; N, 5.80.
O-(2,3,4,6-Tetra-O-benzyl-D-glucopyranosyl) Dichloro-cyanoacetimi-
date (2c). To a solution of 2,3,4,6-tetra-O-benzyl-D-glucopyranose 1c (1.55 g,
2.87 mmol) in dichloromethane (10 mL) was added dichloromalonitrile
(0.8 mL, 7.78 mmol) and three drops of DBU. After 30 min the reaction
mixture was worked up and purified as described for compound 2d, furnishing
essentially only a-product 2c (1.26 g, 68%) as colorless oil. TLC (petroleum
1
ether/diethyl ether 3:2): Rf ¼ 0.36. H NMR (250 MHz, CDCl3): d 8.62 (s, 1H,
NH), 7.07–7.31 (m, 20H, Ph), 6.51 (dd, J1,2 ¼ 3.4 Hz, 1H, 1-H), 5.33–4.36
(m, 8H, 4 CH2Ph), 4.01 (dd, J3,2 ¼ J3,4 ¼ 9.4 Hz, 1H, 3-H), 3.94 (m, 1H, 4-H),
3.73 (dd, J2,1 ¼ 3.4, J2,3 ¼ 9.4 Hz, 1H, 2-H), 3.79–3.56 (m, 2H, 5-H, 2 6-H).

U. Schmelzer et al.
230
O-(2,3,4,6-Tetra-O-benzyl-D-galactopyranosyl) Dichloro-cyanoacetimi-
date (2d). To a solution of 1d (1.55 g, 2.87 mmol) in dichloromethane were
added dichloromalonitrile (0.8 mL, 7.78 mmol) and three drops of DBU. After
stirring for 30 min the reaction mixture was concentrated under reduced
pressure. Purification by flash chromatography (petroleum ether/diethyl
ether 3:2) furnished essentially only a-product 2d (1.17 g, 60%) as a colorless
oil. TLC (petroleum ether/diethyl ether 3:2): Rf ¼ 0.45. [a]D ¼ þ39.4 (c 2.0,
1
CHCl3). H NMR (250 MHz, CDCl3): d 8.58 (bs, 1H, NH), 7.38–7.19 (m, 10H,
Ph), 6.54 (d, J1,2 ¼ 3.4 Hz, 1H, 1-H), 4.98–4.36 (m, 8H, 4 CH2Ph), 4.23 (dd,
J2,1 ¼ 3.4, J2,3 ¼ 9.6 Hz, 1H, 2-H), 4.14 (t, Jt ¼ 6.6 Hz, 1H, 5-H), 4.03–3.92
(m, 2H, 3-H, 4-H), 3.61–3.47 (m, 2H, 2 6-H).
Decyl 2,3,4,6-Tetra-O-acetyl-b-D-glucopyranoside (4aa). Donor 2a (230 mg,
476 mmol) and 1-decanol (109 mL, 572 mmol) were dissolved in dichloromethane/
hexane (1:1) at 08C. A 0.1 M solution of TMSOTf (115 mL, 11.5 mmol, 0.025 eq) in
dichloromethane was added dropwise. After 1 h stirring at 08C the reaction was
terminated by adding triethylamine and the reaction mixture concentrated
under reduced pressure. Purification by flash chromatography (toluene/
acetone 20:1) furnished 4aa (156 mg, 65%) as a colorless oil. The physical data
correspond with those in ref. 23.
Decyl 2,3,4,6-Tetra-O-acetyl-b-D-galactopyranoside (4ba). 2b (100 mg,
0.21 mmol) and 1-decanol (48 mL, 0.25 mmol) were dissolved in dichloro-
methane/hexane (1:1) (2 mL) and the glycosidation initiated by adding a 0.1
M solution of TMSOTf (50 mL, 5 mmol, 0.025 eq) in dichloromethane at rt.
After 1 h the reaction mixture was quenched with one drop of triethylamine
and concentrated under reduced pressure. Purification by flash chromato-
graphy furnished 4ba (72 mg, 71%) as a colorless oil. The physical data corre-
spond with those in ref. 23.
Benzyl 2,3,4-Tri-O-benzyl-O-(2,3,4,6-tetra-O-acetyl-b-D-galactopyrano-
syl)-(1-6)-a-D-glucopyranoside (4bb). A solution of 2b (200 mg, 414 mmol)
and 3b[20] (269 mg, 497 mmol) in dichloromethane/hexane (1: 2) (3 mL) was
cooled down to 08C and then TMSOTf (10 mmol, 0.025 eq) in dichloromethane
added. After 1 h the reaction mixture was quenched with one drop of triethyl-
amine and concentrated under reduced pressure. Purification by flash chromato-
graphy furnished 4bb (296 mg, 82%) as a colorless oil. TLC (petroleum ether/ethyl
acetate 2:1): Rf ¼ 0.27. [a]D ¼ þ29.9 (c 1.0, CHCl3). 1H NMR (250 MHz, CDCl3):
d 5.38–5.37 (dd, 1H, 4b-H), 5.29 (dd, J2b,1b ¼ 8.1, J2b,3b ¼ 10.4 Hz, 1H, 2b-H),
5.00 (dd, J3b,2b ¼ 10.4, J3b,4b ¼ 4.5 Hz, 1H, 3b-H), 4.81 (d, J1a,2a ¼ 4.0 Hz, 1H,
1a-H), 5.03–4.51 (m, 8H, 4 CH2Ph), 4.49 (d, J1b,2b ¼ 8.1 Hz, 1H, 1b-H), 4.18–
4.12 (m, 2H, 2 6b-H), 4.08–4.01 (m, 2H, 6a-H, 5b-H), 3.89–3.82 (m, 2H, 4a-H,
5a-H), 3.66 (dd, Jgem ¼ 10.6, J6a,5a ¼ 4.6 Hz, 1H, 6a-H), 3.51 (dd, J2a,1a ¼ 4.0,

Dichloro-cyanoacetimidates as Glycosyl Donors
231
J2a,3a ¼ 9.8 Hz, 1H, 2a-H), 3.45 (dd, J3a,2a ¼ J3a,4a ¼ 9.8 Hz, 1H, 3a-H), 2.12,
2.03, 1.97, 1.95 (4 s, 12H, 4 OAc).
Methyl 2,3,6-Tri-O-benzyl-O-(2,3,4,6-tetra-O-acetyl-b-D-galactopyranosyl)-
(1-4)-a-D-glucopyranoside (4bc). A solution of 2b (200 mg, 414 mmol) and 3c[21]
(231 mg, 497 mmol) in dichloromethane/hexane (1:1) (4 mL) was cooled down to
08C. After addition of 400 mL of a solution of TMSOTf (10 mmol, 0.025 eq) in dichlor-
omethane, immediately one drop of triethylamine was added and the reaction
mixture concentrated under reduced pressure. Purification by flash chromato-
graphy (petroleum ether/ethyl acetate 2:1) furnished 4bc (275 mg, 84%) as a color-
less foam. The physical data correspond with those in ref. 24.
Decyl 2,3,4,6-Tetra-O-benzyl-b-D-galactopyranoside (4da). A solution of
2d (300 mg, 444 mmol) and 1-decanol (110 mL, 577 mmol) in dichloromethane/
hexane (1:1, 5 mL) was cooled to 2408C. Then a 0.1 M solution of TMSOTf
(100 mL, 10 mmol, 0.02 eq) in dichloromethane was added followed by one
drop of triethylamine. The reaction mixture was then concentrated under
reduced pressure. Purification by flash chromatography (petroleum ether/
ethyl acetate 2:1) furnished 4da (275 mg, 84%) as a colorless oil. The structure
of the compound was secured by debenzylation, peracetylation, and comparison
with 4ba. 4da: TLC (petroleum ether/ethyl acetate 4:1): Rf ¼ 0.62. [a]D ¼ –1.2
(c 1.0, CHCl3). 1H NMR (250 MHz, CDCl3): d 7.38–7.23 (m, 20H, Ph), 4.96–4.37
(m, 8H, 4 CH2Ph), 4.34 (d, J1,2 ¼ 7.7 Hz, 1H, 1-H), 3.96–3.90 (m, 1H, 5-H),
CH3), 3.88–3.88 (m, 1H, 4-H), 3.81 (d, J2,1 ¼ 7.7, J2,3 ¼ 9.7 Hz, 1H, 2-H),
3.61–3.43 (m, 5H, 3-H, 2 6-H, CH2), 1.66–1.57 (m, 2H, CH2), 1.25 (bs, 14H, 7
.
CH2), 0.87 (t, Jt ¼ 6.5 Hz, 3H, CH3). C44H56O6 H2O (699.0). Calcd.: C, 75.61;
H, 8.36. Found: C, 75.79; H 8.17.
Benzyl O-(2,3,4,6-Tetra-O-benzyl-a-D-galactopyranosyl)-(1-6)-2,3,4-tri-
O-benzyl-a-D-glucopyranoside (4db-a) and Benzyl O-(2,3,4,6-Tetra-O-
benzyl-b-D-galactopyranosyl)-(1-6)-2,3,4-tri-O-benzyl-b-D-glucopyra-
noside (4db-b). A solution of 2d (200 mg, 296 mmol) and 3b[20] (192 mg,
355 mmol) in dichloromethane/hexane (1:1, 3 mL) was cooled to 2408C. Then
a 0.1 M solution of TMSOTf (100 mL, 10 mmol, 0.03 eq) in dichloromethane
was added and stirred for 30 min. The reaction mixture was quenched with tri-
ethylamine and concentrated under reduced pressure. Purification by flash
chromatography (petroleum ether/ethyl acetate 2:1) furnished 4db-a
(184 mg, 59%) and 4db-b (96 mg, 30%).
4db-a: TLC (petroleum ether/ethyl acetate 4:1): Rf ¼ 0.36. [a]D ¼ þ86.6 (c 1.0,
CHCl3). 1H NMR (250 MHz, CDCl3): d 7.38–7.13 (m, 40H, Ph), 5.01
(d, J1b,2b ¼ 3.4 Hz, 1H, 1b-H), 4.73 (d, J1a,2a ¼ 3.7 Hz, 1H, 1a-H), 5.00–4.33
(m, 16H, 8 CH2Ph), 4.05–3.50 (m, 11H, 2b-H, 3a-H, 3b-H, 4a-H, 4b-H, 5a-H,
5b-H, 2 6a-H, 2 6b-H), 3.49 (dd, J2a,1a ¼ 3.7, J2a,3a ¼ 9.6 Hz, 1H, 2a-H).

U. Schmelzer et al.
232
4db-b: TLC (petroleum ether/ethyl acetate 4:1): Rf ¼ 0.28. 1H NMR (250 MHz,
CDCl3): (7.33–7.13 (m, 40H, Ph), 5.00–4.35 (m, 17H, 1a-H, 8 CH2Ph), 4.33
(d, J1a,2a ¼ 7.7 Hz, 1H, 1b-H), 4.13–3.83 (m, 5H, 3b-H, 4a-H, 4b-H, 5a-H, 5b-
H), 3.66–3.35 (m, 7H, 2a-H, 2b-H, 3a-H, 2 6a-H, 2 6b-H).
Methyl O-(2,3,4,6-Tetra-O-benzyl-a-D-galactopyranosyl)-(1-4)-2,3,6-tri-
O-benzyl-a-D-glucopyranoside (4dc). A solution of 2d (280 mg, 414 mmol)
and 3d[22] (130 mg, 497 mmol) in dichloromethane/hexane (1:1, 4 mL) was
cooled down to 2408C. Then a 0.1 M solution of TMSOTf (300 mL, 30 mmol,
0.07 eq) in dichloromethane was added. One drop of triethylamine was added
and the reaction mixture concentrated under reduced pressure. Purification
by flash chromatography (petroleum ether/ethyl acetate 4:1) furnished 4dc
(318 mg, 73%) as colorless oil. The physical data are in accordance with the
literature.[28]
Methyl
O-(2,3,4,6-Tetra-O-benzyl-a/b-D-glucopyranosyl)-(1-4)-2,3,6-
solution of 2c (300 mg,
tri-O-benzyl-a-D-glucopyranoside (4cc).
A
444 mmol) and 3c[21] (248 mg, 533 mmol) in dichloromethane/hexane (1:1,
4 mL) was cooled down to 2408C. Then 200 mL of a solution of TMSOTf
(20 mmol, 0.05 eq) in dichloromethane was added. After 30 min two drops of tri-
ethylamine were added and the reaction mixture concentrated under reduced
pressure. Purification by flash chromatography (petroleum ether/ethyl acetate
4:1) furnished 4cc (535 mg, 95%) as colorless oil; anomeric mixture (a/b ¼ 4:1).
The physical data are in accordance with the literature.[25]
1,2:5,6-Di-O-isopropylidene-O-(2,3,4,6-tetra-O-benzyl-a-D-glucopyrano-
syl)-(1-3)-a-D-glucofuranose (4cd-a) and 1,2:5,6-Di-O-isopropylidene-O-
(2,3,4,6-tetra-O-benzyl-b-D-glucopyranosyl)-(1-3)-a-D-glucofuranose
(4cd-b). A solution of 2c (300 mg, 444 mmol) and 3d[22] (130 mg, 497 mmol) in
dichloromethane/hexane (1 : 1, 6 mL) was cooled down to 2408C. Then a 0.1
M solution of TMSOTf (100 mL, 10 mmol, 0.02 eq) in dichloromethane was
added dropwise. After adding three drops of triethylamine, the reaction
mixture was concentrated under reduced pressure. Purification by flash
chromatography (petroleum ether/ethyl acetate 4:1) furnished 4cd-a
(104 mg, 30%) and 4cd-b (207 mg, 60%). The physical data are in accordance
with the literature.[26,27]
3-O-(2,3,4,6-Tetra-O-benzyl-a-D-galactopyranosyl)-(1-3)-1,2:5,6-di-O-iso-
propylidene-a-D-glucofuranose (4dd-a) and 3-O-(2,3,4,6-tetra-O-
benzyl-b-D-galactopyranosyl)-(1-3)-1,2:5,6-di-O-isopropyliden-a-D-glu-
cofuranose (4dd-b). A solution of 2d (280 mg, 414 mmol) and 3d[22]
(130 mg, 497 mmol) in dichloromethane/hexane (1:1, 6 mL) was cooled
down to 2408C. Then 200 mL of a solution of TMSOTf (20 mmol, 0.05 eq)

Dichloro-cyanoacetimidates as Glycosyl Donors
233
in dichloromethane was added dropwise. The reaction mixture was
quenched with triethylamine and concentrated under reduced pressure.
Purification by flash chromatography (petroleum ether/ethyl acetate 4:1)
furnished 4dd-a (69 mg, 21%) and 4dd-b (202 mg, 62%) as colorless oils
(a/b ratio ¼ 1:3). The physical data are in accordance with the
literature.[29]
Dimethylthexylsilyl 6-O-Acetyl-2,3,4-tri-O-benzyl-b-D-glucopyranose
(6). To a stirred solution of hemiacetal 5[30] (13.00 g, 26.42 mmol) and imida-
zole (2.70 g, 39.63 mmol) in dry DMF (60 mL) was slowly added
dimethylthexylsilyl chloride (6.16 mL, 31.70 mmol) at rt and the mixture
was continuously stirred for 17 h. The mixture was then poured into ice
water (200 mL) and extracted with CH2Cl2 (3 ꢁ 50 mL). The
combined organic layers were dried over anhydrous Na2SO4, filtered, con-
centrated in vacuo, and purified by flash column chromatography on silica
gel (petroleum ether/:EtOAc 9 : 1) to afford compound 6 (16.17 g) in 97%
yield as a colorless syrup. Rf 0.76 (PE/EtOAc 3:1); [a]D ¼ þ27.4 (c 1.0,
CHCl3); 1H NMR (250 MHz, CDCl3): d 7.40–7.25 (m, 15H, ArH), 5.03–
4.74 (m, 5H, 2.5 PhCH2), 4.68 (d, J1,2 ¼ 7.5 Hz, 1H, 1-H), 4.60
(d, J ¼ 10.8 Hz, 1H, 0.5 PhCH2), 4.39 (dd, J6A,6B ¼ 11.8, J6A,5 ¼ 1.8 Hz, 1H,
H-6A),
4.17
(dd,
J6B,6A ¼ 11.8,
J6B,5 ¼ 5.8 Hz,1H,
H-6B),
3.69
(t, J3,2 ¼ J3,4 ¼ 9.0 Hz, 1H, H-3), 3.55–3.50 (m, 2H, H-4,5), 3.42 (dd,
J2,3 ¼ 9.3 Hz, J2,1 ¼ 7.5 Hz, 1H, 2-H), 2.06 (s, 3H, Ac), 1.76–1.65 (m, 1H,
Me2CH), 0.93, 0.92, 0.90 (3 s, 12H, 4 Me), 0.22, 0.20 (2 s, 6H, 2 Me) ppm;
MALDI-MS (positive mode, matrix: DHB) for C37H50O7Si (m/z):
[M þ Na]þ ¼ 657.7; Anal. Calcd for C37H50O7Si (634.9): C, 70.00; H, 7.94.
Found: C, 69.69; H, 7.49.
Dimethylthexylsilyl 2,3,4-Tri-O-benzyl-b-D-glucopyranoside (7). To a
stirred solution of compound 6 (15.95 g, 26.16 mmol) in dry methanol (90 mL)
and CH2Cl2 (10 mL) was added NaOMe (68 mg, 1.26 mmol) at rt and the
mixture was continuously stirred for 23 h. The mixture was then neutralized
with Amberlyst 15 ion exchange resin, filtered, concentrated in vacuo, and
purified by flash column chromatography on silica gel (PE/EtOAc
18:1 ! 12:1) to afford compound 7 (14.89 g) in 91% yield as a colorless syrup.
Rf 0.19 (PE/EtOAc 12:1); [a]D ¼ þ10.2 (c 1.0, CHCl3); 1H NMR (250 MHz,
CDCl3): d 7.30–7.25 (m, 15H, ArH), 4.96–4.59 (m, 7H, 3 PhCH2, 1-H), 3.82
(dd, J6A,6B ¼ 12.0, J6A,5 ¼ 3.0 Hz,1H, H-6A), 3.69–3.61 (m, 2 H), 3.54
(t, J ¼ 9.3 Hz, 1 H), 3.38–3.32 (m, 2 H), 1.75–1.60 (m, 1H, Me2CH), 0.89,
0.88, 0.87 (3 s, 12H, 4 Me), 0.18, 0.17 (2 s, 6H, 2 Me) ppm; MALDI-MS
(positive mode, matrix: DHB) for C35H48O6Si (m/z): [M þ Na]þ ¼ 615.7,
[M þ K]þ ¼ 631.6; Anal. Calcd for C35H48O6Si (592.8): C, 70.91; H, 8.16.
Found: C, 70.66; H, 7.67.

U. Schmelzer et al.
234
Dimethylthexylsilyl
2,3,4-Tri-O-benzyl-6-O-(4-tert-butylbenzyl)-b-D-
glucopyranoside (8a). To a stirred suspension of compound 7 (1.10 g,
˚
1.86 mmol) and molecular sieves (4 A MS, 1.50 g) in dry DMF (10 mL) was
added NaH (89 mg, 2.23 mmol, 60% dispersion in mineral oil) at 08C. Five
minutes later, 4-tert-butylbenzyl bromide (0.41 mL, 2.23 mmol) was added
dropwise and the mixture was continuously stirred for 17 h at rt. The mixture
was then diluted with sat. NaHCO3 (40 mL) and extracted with CH2Cl2
(3 ꢁ 20 mL). The combined organic layers were dried over anhydrous
Na2SO4, filtered, concentrated in vacuo, and purified by flash column chromato-
graphy on silica gel (PE/EtOAc 30:1 ! 20:1) to afford compound 8a (1.31 g) in
95% yield as a colorless syrup. Rf 0.59 (PE/EtOAc 12:1); [a]D ¼ þ17.9 (c 1.0,
1
CHCl3); H NMR (250 MHz, CDCl3): d 7.40–7.21 (m, 19H, ArH), 5.02–4.51
(m, 9H, 4 ArCH2, H-1), 3.71–3.60 (m, 4 H), 3.47–3.38 (m, 2 H), 1.78–1.65
(m, 1H, Me2CH), 1.32 (s, 9H, Me3C), 0.93, 0.92, 0.91, 0.90, 0.89 (5 s, 12H,
4Me), 0.24, 0.21 (2 s, 6H, 2 Me) ppm; MALDI-MS (positive mode, matrix:
DHB) for C46H62O6Si (m/z): [M þ Na]þ ¼ 761.7, [M þ K]þ ¼ 777.7; Anal.
Calcd for C46H62O6Si (739.1): C, 74.76; H, 8.46. Found: C, 74.79; H, 8.25.
Dimethylthexylsilyl 2,3,4-Tri-O-benzyl-6-O-(4-methylbenzyl)-b-D-gluco-
pyranoside (8b). Compound 8b was prepared using the same protocol as that
for preparing compound 8a. 8b: 1.37 g (97%), colorless syrup. Rf 0.69 (PE/
EtOAc 12 : 1); [a]D ¼ þ14.4 (c 1.0, CHCl3); 1H NMR (250 MHz, CDCl3): d 7.40–
7.21 (m, 19H, ArH), 5.02–4.51 (m, 9H, 4 ArCH2, 1-H), 3.71–3.60 (m, 4H),
3.47–3.38 (m, 2H), 1.78–1.65 (m, 1H, Me2CH), 1.32 (s, 9H, Me3C), 0.93, 0.92,
0.91, 0.90, 0.89 (5 s, 12H, 4 Me), 0.24, 0.21 (2 s, 6H, 2 Me) ppm; MALDI-MS
(positive mode, matrix: DHB) for C43H56O6Si (m/z): [M þ Na]þ ¼ 719.9; Anal.
Calcd for C43H56O6Si (697.0): C, 74.10; H, 8.10. Found: C, 73.99; H, 7.82.
2,3,4-Tri-O-benzyl-6-O-(4-tert-butylbenzyl)-D-glucopyranose (9a). To a
stirred solution of compound 8a (790 mg, 1.07 mmol) and AcOH (240 mL,
.
4.19 mmol) in dry THF (6 mL) in a Teflon flask was added TBAF 3 H2O
(4 mL, 1 mmol/mL THF solution) at 08C and the mixture was continuously
stirred for 24 h at rt. The mixture was then diluted with sat. NaHCO3
(60 mL) and extracted with CH2Cl2 (3 ꢁ 30 mL). The combined organic
layers were dried over anhydrous Na2SO4, filtered, concentrated in vacuo,
and purified by flash column chromatography on silica gel (PE/EtOAc 4:1) to
afford compound 9a (637 mg) in quant. yield as a white solid. Rf 0.21 (PE/
1
EtOAc 4 : 1); a/b ¼ 37 : 10; H NMR (250 MHz, CDCl3): d 7.34–7.13 (m, 19H,
ArH), 5.26 (t, J ¼ 2.5 Hz, 0.79H, H-1a), 4.97–4.42 (m, 8.21H, 4 ArCH2,
H-1b), 4.05–3.36 (m, 6H, H-2,3,4,5,6), 3.13, 2.88 (2 br s, 1H, OH), 1.29, 1.27
(2 s, 9H, Me3C) ppm; MALDI-MS (positive mode, matrix: DHB) for C38H44O6
(m/z): [M þ Na]þ ¼ 619.8, [M þ K]þ ¼ 635.8; Anal. Calcd for C38H44O6
(596.8): C, 76.48; H, 7.43. Found: C, 76.25; H, 7.22.

Dichloro-cyanoacetimidates as Glycosyl Donors
2,3,4-Tri-O-benzyl-6-O-(4-methylbenzyl)-D-glucopyranoside (9b).
235
Compound 9b was prepared using the same protocol as that for preparing
compound 9a. 9b: 952 mg (92%), white solid. Rf 0.50 (PE/EtOAc 4:1); a/
b ¼ 8:5; 1H NMR (250 MHz, CDCl3): d 7.42–7.10 (m, 19H, ArH), 5.24
(d, J ¼ 3.5 Hz, 0.62H, H-1a), 4.98–4.41 (m, 8.38H, 4 ArCH2, H-1b), 4.06–
3.37 (m, 6H, H-2,3,4,5,6), 3.13, 2.86 (2 br s, 1H, OH), 2.34, 2.32 (2 s, 3H, Me)
ppm; MALDI-MS (positive mode, matrix: DHB) for C35H38O6 (m/z):
[M þ Na]þ ¼ 578.2; Anal. Calcd for C35H38O6 (554.7): C, 75.79; H, 6.91.
Found: C, 75.84; H, 7.08.
2,3,4-Tri-O-benzyl-6-O-(4-tert-butylbenzyl)-D-glucopyranosyl Trichlor-
oacetimidate (10a). To a stirred solution of hemiacetal 9a (413 mg,
0.69 mmol) and CCl3CN (510 mL, 5.10 mmol) in dry CH2Cl2 (3 mL) were
added three drops of DBU at rt. After 30 min the mixture was concentrated
in vacuo and purified by flash column chromatography on silica gel (toluene/
EtOAc/Et3N 200:5:2 ! 100:4:1) to afford 10a (472 mg) in 92% yield as a
slightly yellow syrup. Rf 0.59 (toluene/EtOAc 10:1); a/b ¼ 23:1; 1H NMR
(250 MHz, CDCl3): d 8.72, 8.57 (2 s, 1H, NH), 7.35–7.13 (m, 19H, ArH), 6.52,
5.83 (2 d, J1a,2 ¼ 3.3, J1b,2 ¼ 7.5 Hz, 1H, H-1a,b), 4.98–4.40 (m, 8H, 4
ArCH2), 4.08–3.62 (m, 6H, H-2,3,4,5,6), 1.29, 1.27 (2 s, 9H, Me3C) ppm;
MALDI-MS (positive mode, matrix: DHB) for C40H44Cl3NO6 (m/z): [M – CCl3-
CN þ Na]þ ¼ 619.6, [M – CCl3CN þ K]þ ¼ 635.8.
2,3,4-Tri-O-benzyl-6-O-(4-methylbenzyl)-D-glucopyranosyl
Dichloro-
cyanoacetimidate (10b). To a stirred solution of hemiacetal 9b (295 mg,
0.53 mmol) and Cl2C(CN)2 (140 mL, 1.33 mmol) in dry CH2Cl2 (3 mL) were
added two drops of DBU at rt. After 30 min the mixture was concentrated
under vacuo and purified by flash column chromatography on silica gel
(toluene/EtOAc/Et3N 200:5:2 ! 100:4:1) to afford 10b (330 mg) in 90% yield
as a colorless syrup. Rf 0.56 (toluene/EtOAc 10:1); a/b ¼ 27 : 1; 1H NMR
(250 MHz, CDCl3): d 8.64, 8.27 (2 s, 1H, NH), 7.43–7.10 (m, 19H, ArH), 6.54,
5.79 (2d, J1a,2 ¼ 3.5, J1b,2 ¼ 7.5 Hz, 1H, H-1a,b), 5.02–4.35 (m, 8H,
4 ArCH2), 4.06–3.55 (m, 6H, H-2,3,4,5,6), 2.30, 2.32 (2 s, 3H, Me) ppm;
MALDI-MS (positive mode, matrix: DHB) for C38H38Cl2N2O6 (m/z):
[M þ Na]þ ¼ 711.2, [M þ K]þ ¼ 727.1.
Methyl
2,3,4-Tri-O-benzyl-6-O-(4-tert-butylbenzyl)-a-D-glucopyrano-
syl-(1-6)-2,3,4-tri-O-benzyl-a-D-glucopyranoside (12aa) and Methyl
2,3,4-Tri-O-benzyl-6-O-(4-tert-butylbenzyl)-b-D-glucopyranosyl-(1-6)-
2,3,4-tri-O-benzyl-b-D-glucopyranoside (12ab). General procedure for gly-
cosylations: Trichloroacetimidate 10a (89 mg, 0.12 mmol), acceptor 11[31]
(46 mg, 0.10 mmol), and a stirrer were combined in a flask (10 mL) and then
dried in high vacuo while the flask was being kept in a 458C oil bath. Two

U. Schmelzer et al.
236
hours later, the flask was cooled by air to ambient temperature and filled with
argon, and anhydrous CH2Cl2 (1.0 mL) was added. Then the mixture was
cooled to 2408C and TMSOTf (94 mL, 0.05 eq) was slowly added. Thirty
minutes later, TLC showed the completion of the glycosylation. The reaction
was quenched with one drop of Et3N and concentrated. The residue was
purified by flash column chromatography on silica gel (toluene/EtOAc
30:1 ! 20:1 ! 10:1) to afford a mixture of 12aa and 12ab (84 mg 12aa/
1
12ab ꢀ 1 : 4 as estimated by H NMR) in 82% yield as a colorless syrup. The
mixture of 12aa and 12ab was subjected again to flash column chromato-
graphy on silica gel (hexane/EtOAc 5:1 ! 4:1) to afford a little pure 12ab
(15 mg). Pure 12aa could not be obtained. 12ab: Rf 0.15 (toluene/EtOAc
1
10:1); [a]D ¼ þ16.7 (c 1.0, CHCl3); H NMR (250 MHz, CDCl3): d 7.38–7.19
(m, 34H, ArH), 5.02–4.48 (m, 15H, 7 ArCH2, H-1a), 4.37 (d, J1b,2b ¼ 7.8 Hz,
1H, H-1b), 4.21 (dd, Jgem ¼ 10.8, J6a,5a ¼ 1.5 Hz, 1H, H-6a), 4.02
(t, J ¼ 9.3 Hz), 3.88–3.81 (m, 1H, H-5a), 3.78–3.42 (m, 9 H), 3.35 (s, 3H,
MeO), 1.31 (s, 3H, Me3C) ppm; 13C NMR (62.5 MHz, CDCl3): d 150.5, 138.8,
138.6, 138.3, 138.1, 135.2, 128.3, 128.1, 127.9, 127.8, 127.7, 127.6, 127.5,
125.2, 103.8, 98.0, 84.8, 82.1, 82.0, 79.9, 78.0, 77.9, 77.2, 75.6, 75.1, 74.9,
74.8, 73.3, 69.9, 69.0, 68.5, 55.2, 34.5, 31.3; MALDI-MS (positive mode,
matrix: DHB) for C66H74O11 (m/z): [M þ Na]þ ¼ 1065.0, [M þ K]þ ¼ 1081.0;
.
Anal. Calcd for C66H74O11 H2O (1061.3): C, 74.24; H, 7.05. Found: C, 74.54;
H, 6.92.
Methyl 2,3,4-Tri-O-benzyl-6-O-(4-methylbenzyl)-a-D-glucopyranosyl-
(1-6)-2,3,4-tri-O-benzyl-a-D-glucopyranoside (12ba) and Methyl 2,3,4-
Tri-O-benzyl-6-O-(4-methylbenzyl)-b-D-glucopyranosyl-(1-6)-2,3,4-tri-O-
benzyl-b-D-glucopyranoside (12bb). As described for 12a, dichloro-cyanoa-
cetimidate 10b (128 mg, 0.19 mmol) reacted with acceptor 11[31] (72 mg,
0.16 mmol) in the presence of catalyst TMSOTf (150 mL, 0.05 eq) to afford a
mixture of 12ba and 12bb (131 mg, 12ba/12bbꢀ1:4 as estimated by 1H
NMR) in 84% yield as a white solid. The mixture of 12ba and 12bb was sub-
jected again to flash column chromatography on silica gel (hexane/EtOAc
5:1 ! 4:1) to afford some pure 12bb (21 mg). 12bb: Rf 0.14 (toluene/EtOAc
1
10:1); [a]D ¼ þ 19.5 (c 1.0, CHCl3); H NMR (250 MHz, CDCl3): d 7.33–7.10
(m, 34H, ArH), 5.00–4.46 (m, 15H, 7 ArCH2, H-1a), 4.35 (d, J1b,2b ¼ 7.8 Hz,
1H, H-1b), 4.19 (dd, Jgem ¼ 10.5, J6a,5a ¼ 1.5 Hz, 1H, H-6a), 4.00
(t, J ¼ 9.3 Hz), 3.86–3.81 (m, 1H, H-5a), 3.76–3.42 (m, 9 H), 3.33 (s, 3H,
MeO), 2.31 (s, 3H, Me) ppm; 13C NMR (62.5 MHz, CDCl3): d 138.8, 138.5,
138.4, 138.1, 137.1, 135.1, 129.0, 128.4, 128.3, 128.1, 127.9, 127.8, 127.7,
127.6, 127.4, 103.8, 98.0, 84.8, 82.0, 81.9, 79.8, 78.0, 77.9, 75.6, 75.0, 74.9,
74.8, 73.3, 69.8, 68.7, 55.1, 21.1; MALDI-MS (positive mode, matrix: DHB)
for C63H68O11 (m/z): [M þ Na]þ ¼ 1023.3; Anal. Calcd for C63H68O11 (1001.2):
C, 75.58; H, 6.85. Found: C, 75.42; H, 6.85.

Dichloro-cyanoacetimidates as Glycosyl Donors
237
ACKNOWLEDGEMENTS
This work was supported by the Deutsche Forschungsgemeinschaft and the
Fonds der Chemischen Industrie. We are grateful to Prof. Dr. H. Fischer and
Dr. G. Roth for the X-ray analysis.
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[20] For compound 3b see: Adams, P.R.; Harrison, R.; Inch, T.D.; Rich, P. Dehydrogena-
tion of the phosphonate analogue of glucose 6-phosphate by glucose 6-phosphate
dehydrogenase. Biochem. J. 1976, 155, 1–4.
[21] For compound 3c see: Garegg, P.J.; Hultberg, H.; Wallin, S. A novel reductive ring-
opening of carbohydrate benzylidene acetals. Carbohydr. Res. 1982, 108, 97–101.
[22] For compound 3d see: Schmidt, O.T. Isopropylidene derivatives. In Methods in
Carbohydrate Chemistry; Whistler, R.L., Wolfram, L., Eds.; Academic Press:
New York, 1963; Vol. II, 320–321.
[23] Klotz, W. Untersuchungen zur anomeren O-Alkylierung von Hexosen und
¨ ¨ ¨
Reaktivitat und Regioselektivitat. Dissertation, Universitat
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Konstanz, Verlag Hartung-Gorre: Konstanz, 1994.
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1,2-cis-disaccharides. J. Am. Chem. Soc. 1977, 99, 6762–6763.
[26] Schmidt, R.R.; Michel, J. O-(a-D-Glucopyranosyl)-trichloracetimidate as glycosyl
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¨
[27] Schmidt, R.R.; Behrendt, M.; Topfer, A. Nitriles as solvents in glycosylation reac-
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AlCl3, reagent. Carbohydr. Res. 1975, 44, 1–11.