Synthesis of deoxy glycosides under neutral conditions in LiClO4/solvent mixtures

Article abstract of DOI:10.1055/s-1999-3651

2-Deoxy- and 2,6-dideoxyglycosyl trichloroacetimidates, phosphites and fluorides are efficiently activated in 0.1M metal perchlorate/solvent mixtures, i.e. without the need for an additional promoter like a strong Lewis acid or a heavy metal salt. Under these neutral conditions they react with different glycosyl acceptors to give oligosaccharides, amino acid glycosides and cholesteryl glycosides in high yields and with pronounced stereoselectivity. For 3,4,6-tri-O-benzyl protected 2-deoxy glucose the highest yields were observed with the α-imidate, however, the anomer ratio was highest if the corresponding glycosyl fluoride was used. The stereoselectivity was not significantly influenced by the solvent and the metal ion, the yield was highest in 0.1M solutions of LiClO₄ in diethyl ether. Under these gentle conditions also 2-deoxy-L-fucosyl fluoride and D- digitoxosyl fluoride react with different O-silylated glycosyl acceptors to give sensitive 2,6-dideoxyglycosides with preparatively useful results.

Full text of DOI:10.1055/s-1999-3651

PAPER
1411
Synthesis of Deoxy Glycosides Under Neutral Conditions in LiClO4/Solvent
Mixtures
Heidrun Schene, Herbert Waldmann*
Universität Karlsruhe, Institut für Organische Chemie, Richard-Willstätter-Allee 2, D-76128, Karlsruhe, Germany
Fax+49(721)6084825; E-mail: waldmann@ochhades.chemie.uni-karlsruhe.de
Received 18 March 1999
jacent to the anomeric center is lacking that may direct the
Abstract: 2-Deoxy- and 2,6-dideoxyglycosyl trichloroacetimi-
steric course of the glycosidation reaction.
dates, phosphites and fluorides are efficiently activated in 0.1M
metal perchlorate/solvent mixtures, i. e. without the need for an ad-
ditional promoter like a strong Lewis acid or a heavy metal salt. Un-
For the stereoselective synthesis of 2-deoxy-a-glycosides
the latter problem mostly is circumvented by electrophile
der these neutral conditions they react with different glycosyl
mediated addition of acceptor alcohols to the double bond
acceptors to give oligosaccharides, amino acid glycosides and cho-
of glycals followed by reductive removal of the C-2-sub-
lesteryl glycosides in high yields and with pronounced stereoselec-
stituent.4 For the construction of b-configured 2-deoxy-
tivity. For 3,4,6-tri-O-benzyl protected 2-deoxy glucose the highest
glycosides the use of glycosyl donors with equatorial 2-
substituents acting as neighboring group5 and of 1,2-
anhydropyranoses6 followed by reductive removal of the
2-substituent has provided solutions to the problem.
Clearly, the application of direct methods for the efficient
and highly stereoselective construction of 2-deoxy- and
2,6-dideoxyglycosides is highly desirable. For this pur-
pose the Koenigs–Knorr reaction employing the insoluble
silver silicate,7 the Lewis acid-mediated activation of gly-
cosyl phosphites and phosphoramidates,8 and the activa-
tion of glycosyl sulfoxides in the presence of a Lewis
acid9 were developed recently. In the light of the pro-
nounced acid-sensitivity of deoxyglycosides and the
drawbacks associated with the use of toxic and expensive
heavy metal salts, the development of alternative methods
that proceed under very mild, preferably neutral condi-
tions and without the use of strong Lewis acids or other
promotors is of great interest.
yields were observed with the a-imidate, however, the anomer ratio
was highest if the corresponding glycosyl fluoride was used. The
stereoselectivity was not significantly influenced by the solvent and
the metal ion, the yield was highest in 0.1M solutions of LiClO4 in
diethyl ether. Under these gentle conditions also 2-deoxy-L-fucosyl
fluoride and D-digitoxosyl fluoride react with different O-silylated
glycosyl acceptors to give sensitive 2,6-dideoxyglycosides with
preparatively useful results.
Key words: deoxyglycosides, glycosylations, LiClO4/diethyl ether
mixtures, carbohydrates, oligosaccharides
Introduction
Glycosides of 2-deoxy- and 2,6-dideoxycarbohydrates
occur in various natural products. For instance they form
characteristic structural elements of antitumor drugs like
the anthracyclins, aureolic acid, calicheamicin and espe-
ramicin, of antibiotics active against Gram positive bacte-
ria, like the orthosomycins, and of cardiac glycosides used
in the treatment of cardiac insufficiency.1 Whereas the
therapeutic effect of these drugs is mediated by the agly-
con, the glycosidic part influences the pharmacokinetic
properties of the physiologically active compounds. The
development of new drugs with altered glycosidic parts or
aglycons is actively being pursued. For instance 2-deoxy-
L-fucose is employed in the development of so called class
II anthracyclin antibiotics.1,2 Also, digitoxosides in which
the aglycons found in the natural Digitalis glycosides are
replaced by analogs are of great interest as new and safer
drugs for the treatment of cardiac insufficiency.3 Due to
this biological relevance the development of methods for
the efficient and stereoselective construction of deoxygly-
cosidic linkages is of great relevance to organic synthesis,
medicinal and bioorganic chemistry.1
We have recently reported that solutions of LiClO4 in or-
ganic reaction media favor the formation of glycosyl cat-
ions by detachment of suitable leaving groups from
various glycosyl donors and thus are eminently suitable
for O-glycoside synthesis under very mild conditions.10 In
these solvent systems glycosyl halides, trichloroacetimi-
dates, phosphates and phosphites are activated under neu-
tral conditions and participate as glycosyl donors in
glycosylation reactions with different glycosyl acceptors.
In this paper we report on the application of this method
for the construction of 2-deoxy- and 2,6-dideoxyglyco-
sides (Scheme 1).11
Results and Discussion
Our previous investigations on the use of LiClO4/solvent
mixtures for glycoside synthesis under neutral conditions
had revealed that glycosyl trichloroacetimidates and gly-
cosyl fluorides12 are particularly advantageous glycosyl
donors in these reaction media. Therefore, the corre-
sponding glycosyl donors 1–4 derived from benzyl-pro-
In comparison to the synthesis of other glycosides 2-de-
oxyglycoside synthesis is particularly challenging, since
2-deoxyglycosides on the one hand are more acid labile.
On the other hand a stereodirecting neighboring group ad-
Synthesis 1999, No. SI, 1411–1422 ISSN 0039-7881 © Thieme Stuttgart · New York

1412
H. Schene, H. Waldmann
PAPER
(a:b = 25:1) was obtained in quantitative yield. If K2CO3
was employed as base the corresponding b-anomer 2 was
formed in excess14 (quantitative yield, a:b = 1:8; see the
experimental part).
Scheme 1 Synthesis of 2-deoxyglycosyl saccharides in metal (Met)
perchlorate/diethyl ether mixtures
tected 2-deoxyglucose (Figure 1) were employed to
determine if deoxyglycosides could be built up in solu-
tions of metal perchlorates in organic solvents. Alcohols
7–12 were used as model glycosyl acceptors. 2-Deoxyglu-
cosyl-a-trichloroacetimidate 1 was synthesized by depro-
tonation of 3,4,6-tri-O-benzyl-2-deoxyglucopyranose13
with NaH and subsequent treatment with trichloroacetoni-
trile according to the method introduced by R. R. Schmidt
et al.14 An a/b-mixture with the a-anomer predominating
Figure 2 Glycosyl acceptors employed in the glycosylation reac-
tions
Upon treatment of a-configured glycosyl donor 1 with se-
lectively deprotected glucosyl acceptor 7a in differently
concentrated solutions of LiClO4 in diethyl ether the cor-
responding disaccharide 13 was formed smoothly and in
high yield. Variation ot the LiClO4 concentration between
0.03 M and 0.5 M revealed that the yield was highest in
0.1 M LiClO4/diethyl ether (Table 1, entry 1). Therefore
all further glycosylations were conducted in 0.1 M solu-
tions (Table 1). Under these conditions deoxyglucosyl
disaccharide 13 was obtained in 89% isolated yield and
with an a/b ratio of 1.5:1. Use of the more reactive b-gly-
cosyl donor did not give an improved yield and the a/b ra-
tio was very similar (Table 1, entry 2). Also variation of
the solvent and the metal counterion did not significantly
change the picture. In toluene, CH3CN and CH2Cl2 and
also with Mg(ClO4)2 and Ba(ClO4)2 the stereoselectivity
was very similar. However, the yield was consistently
lower (Table 1, entries 3–7). In particular, the finding that
in CH3CN the a/b ratio remains unchanged is surprising.
Obviously, the “nitrile-effect”15 that was observed in the
activation of the analogous glucosyl trichloroacetimidate
in LiClO4/diethyl ether10a,b is not operating in the deoxy
case. In order to determine the influence of the perchlorate
anion, solutions of LiN(Tf)2,16 LiBF4 and LiPF6 in diethyl
ether were investigated as reaction media. For the
Figure 1 Glycosyl donors employed in the synthesis of 2-deoxy
and 2,6-dideoxyglycosides
Synthesis 1999, No. SI, 1411–1422 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of Deoxy Glycosides Under Neutral Conditions in LiClO4/Solvent Mixtures
1413
Table 1 Results of the Glycosylations in 0.1M Solutions of
MetClO4 Employing Donors 1 and 2 and Acceptor 7a To Give
Glycoside 13
tained from 3,4,6-tri-O-benzyl-2-deoxyglucose according
to a published procedure8b and fluoride 4 was synthesized
from this selectively deprotected deoxyglucose derivative
by treatment with diethylaminosulfur trifluoride18
(DAST; see the experimental part).
Entry Donora Promoter
Solvent
Yield
(%)b
Anomer
ratio
(a:b)c
Deoxyglycosyl phosphite 3 was also activated in 0.1 M
LiClO4/diethyl ether and reacted with glycosyl acceptors
7a and 8a to give disaccharides 13 and 14 in 56% and 43%
yield and with a/b ratios of 3.5:1 and 4.2:1 respectively.
Thus, although a higher preference for the a-anomer
could be recorded with this glycosyl donor the situation
was not improved to a satisfying degree. The use of 2-
deoxyglucosyl fluoride 4, however, led to significantly
higher anomer ratios. Glycosyl donor 4 is also activated in
1M LiClO4 in diethyl ether under very mild conditions. It
reacts with selectively deprotected glucose derivative 7a,
galactosyl alcohol 8a and cholesterol 10a to give glyco-
sides 13, 14 and 16 in yields of 41–65% (Table 3). More
gratifyingly, a pronounced preference for the a-anomer is
observed. Thus, glucosyl disaccharide 13 is formed with
an a/b ratio of 13.4:1 whereas with the imidate 1 only a
value of 1.5:1 was recorded (compare Table 1, entry 1 and
Table 3, entry 1). Similarly for galactosyl disaccharide 14
the anomer ratio raised to 6:1 (as compared to 2:1 for the
imidate). Cholesteryl glycoside 16 prepared from fluoride
4 displayed an a/b ratio of 11.4:1 whereas if imidate 1 was
used the two anomers were fomed in equal amounts (Ta-
1
2
3
4
5
6
7
8
9
1
2
1
1
1
1
1
1
1
1
LiClO4
LiClO4
LiClO4
LiClO4
LiClO4
Ba(ClO4)2
Mg(ClO4)2
LiN(SO2CF3)2 Et2O
LiBF4
LiPF6
Et2O
Et2O
89
78
69
68
75
66
43
31
75
29
1.5:1
1.1:1
1.8:1
1.5:1
1.8:1
1.8:1
1.3:1
1.3:1
1.6:1
3.6:1
toluene
CH3CN
CH2Cl2
CH3CN
CH2Cl2
Et2O
Et2O
10
a The donors 1 (a:b = 25:1) and 2 (a:b = 1:8) were used as anomeric
mixtures.
b Chromatographically purified glycoside 13.
c The ratio was determined by 1H or 13C NMR.
hexafluorophosphate the stereoselectivity was signifi-
cantly higher (Table 1, enty 10), but the yield was inferior
in all three cases. Thus, the best results were obtained with
a-deoxyglucosyl imidate 1 in 0.1 M solutions of LiClO4 in
diethyl ether. Therefore, all further glycoside syntheses
with this donor were carried out under these conditions.
In order to determine the scope of this new method, imi- ble 2, entry 3 and Table 3, entry 3). Thus, although with
date 1 was coupled with glycosyl acceptors 8–11. In the fluoride 4 yields are lower than with imidate 1, the higher
course of the ensuing reactions galactosyl glycoside 14, stereoselectivity overcompensates this loss in reactivity.
serine glycoside 15 and cholesterol derivative 16 were
formed in high yields and with a/b ratios ranging from
2.4:1 to 1:1 (Table 2, entries 1–3). Deoxyglucosyl disac-
In order to extend the scope of the method established as
described above, the synthesis of 2,6-dideoxyglycosides
in LiClO4/diethyl ether was investigated. Since glycosides
of 2-deoxy-L-fucose and of D-digitoxose are targets of
charide 17 was obtained in lower yield, however, the a-
anomer was formed with complete stereoselectivity (Ta-
current interest (see the Introduction), these two carbohy-
ble 2, entry 4). These results demonstrate that 2-deoxyim-
drates were chosen for further studies. In the light of the
finding that 2-deoxyglucosyl fluoride was the most ad-
vantageous of the 2-deoxyglucosyl donors investigated,
the corresponding fluorides 5 and 6 (Figure 1) of 2-de-
idate 1 is efficiently activated in 0.1 M solutions of LiClO4
in diethyl ether in the absence of a strong Lewis acid. As
already pointed out earlier, the rate-accelerating effect of
these reaction media may be attributed to their ability to
oxylfucose and D-digitoxose were prepared (Scheme 2).
stabilize polar or ionic transition states or intermediates
To this end, triacetates 2519 and 2620 were converted into
like glycosyl cations.10,17
diacetylated allyl glycosides 27 and 28. After removal of
Although with imidate 1 the desired glycosides were the acetates, benzyl ether protecting groups were intro-
formed in high yields the stereoselectivity remained most- duced. The allyl glycosides were then cleaved by Rh(I)-
ly low. In an attempt to find glycosyl donors that react mediated isomerisation of the allyl to the 1-propenyl
with higher selectivity the use of deoxyglucosyl phosphite group and subsequent Lewis acid mediated hydrolysis of
3 and of deoxyglucosyl fluoride 4 in the glycosidations the enol ethers formed in this process.21 Finally, the result-
was investigated. Deoxyglucosyl phosphite 3 was ob- ing dideoxycarbohydrates selectively deprotected at the
Table 2 Results of Glycosylations With Glycosyl Imidate 1 in 0.1M
Solutions of LiClO4
Table 3 Results of the Glycosylations with Glycosyl Fluoride 4 in
0.1M Solutions of LiClO4 in Diethyl Ether
Entry Acceptor Solvent Glycoside Yield
(%)
Anomer ratio
(a:b)
Entry
Acceptor
Glycoside
Yield (%)
Anomer ratio
(a:b)
1
2
3
4
8a
9
10a
11
Et2O
CH2Cl2 15
Et2O
Et2O
14
91
57
78
37
2:1
2.4:1
1:1
1
2
3
7a
8a
10a
13
14
16
65
49
41
13.4:1
6:1
11.4:1
16
17
only a
Synthesis 1999, No. SI, 1411–1422 ISSN 0039-7881 © Thieme Stuttgart · New York

1414
H. Schene, H. Waldmann
PAPER
anomeric center were converted into glycosyl fluorides 5
and 6 by treatment with DAST.
As glycosyl acceptors silyl ethers 7b, 8b and 10b were
employed to facilitate the reactions by formation of the
very stable Si–F bond. Lactose acceptor 12 was used to
test if any regioselectivity could be obtained. Upon treat-
ment of benzyl-protected 2-deoxyfucosyl fluoride 5 with
glucose derivative 7b, galactosyl acceptor 8b, cholesteryl
silyl ether 10b and lactose derivative 12 in 0.1 M LiClO4
in diethyl ether, glycosides 18–21 were smoothly formed
in moderate to high yield. In all cases, the anomer ratio
was gratifyingly high (Table 4, entries 1–5). Whereas the
glucose and the galactose disaccharides were obtained
with a/b ratios of 8:1 to 13:1, cholesteryl glycoside 20 and
trisaccharide 21 were formed with complete a-selectivity.
Furthermore, the glycosylation of lactose acceptor 21 pro-
ceeded with complete regioselectivity to deliver exclu-
sively the 4’-deoxyfucosyl trisaccharide. Once more the
use of CH3CN as solvent did not influence the course of
the stereoselection. Glycoside 20 was formed in both di-
ethyl ether and acetonitrile with complete a-selectivity
(Table 4, entries 3 and 4). Thus, under these reaction con-
ditions glycosides of 2-deoxy-L-fucose can be prepared
with high selectivity and the method is applicable to the
construction of oligosaccharides.
D-Digitoxosyl fluoride 6 reacted with glucosyl- and galac-
tosyl silyl ethers 7b and 8b and silylated cholesterol 10b
also under the mild conditions provided by the LiClO4/
ether systems to give the corresponding disaccharides 22
and 23 as well as and the steroid glycoside 24 in satisfying
yields (Table 4, entries 6–8). Whereas with glucose accep-
tor 7b the anomers were formed nearly in a 1:1 ratio, for
galactose disaccharide 23 once more a high a/b ratio was
recorded (Table 4, entries 6 and 7). In the case of choles-
teryl glycoside 24 unexpectedly the b-isomer was formed
in excess (Table 4, entry 8).
In conclusion the results detailed above demonstrate that
in 0.1 M LiClO4/diethyl ether mixtures glycosides of 2-
deoxy- and 2,6-dideoxycarbohydrates are formed in high
yields and with high stereoselectivity. The glycosidation
reactions proceed under neutral conditions and without
need for an additional promoter usually applied in glyco-
Scheme 2. Synthesis of 2,6-dideoxy fluorides 5 and 6
side synthesis, i.e. a strong Lewis acid, a heavy metal salt
or an alkylating reagent.
The LiClO4/diethyl ether method compares favourably
with established methods of 2-deoxyglycoside synthesis.
For instance coupling of in situ generated glycosyl phos-
phates of 2-deoxyglucose with glycosyl acceptors 7a and
8a proceeded in 72% and 79% respectively,22 whereas ac-
tivation of imidate 1 in LiClO4/diethyl ether delivered dis-
accharides 13 and 14 in 89% and 91% yield respectively
(Table 1 and Table 2). The synthesis of these disaccha-
Table 4 Results of the Glycosylations with 2-Deoxyfucosyl Donor
5 and Digitoxosyl Fluoride 6 in 0.1M Solutions of LiClO4 in Organic
Solvents
Entry Donor Accep- Glyco- Solvent Yield Anomer ratio
tor
side
(a:b)
1
2
3
4
5
6
7
8
5
5
5
5
5
6
6
6
7b
18
19
20
20
21
22
23
24
Et2O
Et2O
Et2O
49
75
66
8:1
13:1
8b
10b
10b
12
7b
8b
only a
only a
only a
1:1.3
10:1
rides employing a a pentenyl
thioglycoside23 or
glycoside24 as glycosyl donors and methyl iodide or I(col-
lidine)2ClO4 as promoters proceeded in 68–88% yield. 2-
Deoxyfucosyl glucopyranoside 18 could be built up in
91% yield by employing the dibenzylphosphite of 2-de-
CH3CN 51
Et2O
Et2O
Et2O
Et2O
31
52
61
39
10b
1:4.5
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PAPER
Synthesis of Deoxy Glycosides Under Neutral Conditions in LiClO4/Solvent Mixtures
1415
oxyfucose as glycosyl donor and TMSOTf as promotor,8
whereas it was obtained in LiClO4/diethyl ether in only
49% yield. However in the case of the phosphite donor at
a/b ratio was only 2:1, whereas in LiClO4/diethyl ether it
was significantly higher (8.1:1).
Glycosyl Fluorides 4, 5 and 6; General Procedure
To a solution of 3,4,6-tri-O-benzyl-2-deoxy-D-glucopyranose, 3,4-
di-O-benzyl-2-deoxy-L-fucopyranose or 3,4-di-O-benzyl-2,6-
dideoxy-D-ribohexopyranose (0.1 mmol) in CH2Cl2 (0.4 mL) at
–78 °C was added rapidly under Ar DAST (30.9 mmol) and the so-
lution was stirred for 20 min. The cooling bath was removed and af-
ter 15 min stirring at r.t. TLC indicated completion of the reaction.
In the cases of the fluorides 4 and 5 stirring was continued at 0 °C.
MeOH (0.1 mL) was added to quench the reaction. The solution was
diluted with CH2Cl2 (50 mL), washed with H2O, dried (Na2SO4) and
concentrated in vacuo. The fluorides were used without further pu-
rification.
MPs were recorded on a Büchi 530 melting point apparatus and are
uncorrected. 1H and 13C NMR were measured on a Bruker AC-250,
a Bruker AM-400 or a Bruker DRX-500 spectrometer. Chemical
shifts are expressed in ppm downfield relative to TMS as an internal
standard. Specific optical rotation values were determined on a Per-
kin Elmer polarimeter 241. Mass spectra were obtained with a
Finnigan MAT 90 spectrometer or a PerSeptive Biosystems Voy-
agerTM spectrometer. Elemental analyses were performed on an El-
ementar CHN-Rapid Analyzer. For thin-layer chromatography
(TLC) Macherey-Nagel silica gel ALUGRAM® SIL G/UV254 lay-
ers were used. Flash chromatography was performed with Baker sil-
ica gel (40–60mm). LiPF6 and LiBF4 were obtained from Aldrich
and Fluka as >98% pure solids. LiClO4 (Acros), Mg(ClO4)2 (Fluka),
Ba(ClO4)2 (Merck) and LiN(CF3SO2)2 (3M-company) were dried
extensively in vacuo prior to use. The carbohydrates 3,8b 7a,5j,8b
3,4,6-Tri-O-benzyl-2-deoxy-a/b-D-glucopyranosyl Fluoride (4)
Yellowish oil; yield quantitative; anomeric ratio a:b = 4:1; Rf:0.53
(EtOAc/hexane 1/2).
MS (EI): m/z = 435 [M+-H]. C27H29O4F.
a-Anomer:
1H NMR (500 MHz, CDCl3): d = 1.75 (dt, J2,3 = J2’,2 = 13.7 Hz,
J2,F = 39.8 Hz, 1H, 2-H), 2.43 (dt, J2’,3 = 4.7 Hz, J2,2’ = J2’,F = 13.7
Hz, 1H, 2’-H), 3.62–3.80 (m, 3H, 4-H, 6’-H, 6-H), 3.92–3.99 (m,
2H, 3-H, 5-H), 4.49–4.64 (m, 5H, OCH2Ph), 4.89 (d, Jgem = 10.8 Hz,
1H, OCH2Ph), 5.75 (d, J1,F = 52.0 Hz, 1H, 1-H), 7.18–7.34 (m, 15H,
Ph-H).
8a,25
9,26
1227
and
3,4,6-tri-O-benzyl-2-deoxy-a/b-D-
glucopyranose13 were prepared according to literature procedures.
13C NMR (125.7 MHz, CDCl3): d = 35.15 (1C, JC2,F = 26.6 Hz,
CH2, C-2), 68.24 (1C, CH2, C-6), 72.05, 73.48, 75.05 (3C, CH2,
OCH2Ph), 73.22, 76.39, 77.26 (3C, CH, C-3, C-4, C-5), 106.93 (1C,
Glycosyl Donors
3,4,6-Tri-O-benzyl-2-deoxy-a/b-D-glucopyranosyl Trichloro-
acetimidates (1) and (2)
JC1,F = 216.4 Hz, CH, C-1), 127.65–128.43 (15C, CH, Ph-CH),
These compounds were prepared by analogy to the procedures de-
scribed by R. R. Schmidt et al.14 and used without further purifica-
tion.
137.89, 138.26, 138.28 (3C, Cipso).
Characteristic signals of the b-anomer:
1H NMR (500 MHz, CDCl3): d = 5.38 (dd, J1,2 = 6.8 Hz, J1,F = 52.0
Hz, 1H, 1-H).
13C NMR (125.7 MHz, CDCl3): d = 34.79 (1C, JC2,F = 21.5 Hz,
CH2, C-2), 106.62 (1C, JC1,F = 211.7 Hz, CH, C-1).
3,4,6-Tri-O-benzyl-2-deoxy-b-D-glucopyranosyl Trichloroace-
timidate (2)
Pale yellow oil; yield quantitative; anomeric ratio a:b = 1:8; Rf:0.24
(EtOAc/hexane 1/2). C29H30NCl3O5.
1H NMR (250 MHz, CDCl3): d = 1.90 (q, J1,2 = J2,2’ = J2,3 = 10.9
Hz, 1H, 2-H), 2.53 (ddd, J2’,3 = J2’,1 = 2.4 Hz, J2,2’ = 10.3 Hz, 1H, 2’-
H), 3.63–3.81 (m, 5H, 3-H, 6-H), 4.51–4.72 (m, 5H, OCH2Ph), 4.87
(d, Jgem = 10.8 Hz, 1H, OCH2Ph), 5.86 (dd, J2’,1 = 2.2 Hz, J1,2 = 9.2
Hz, 1H, 1-H), 7.19–7.32 (m, 15H, Ph-H), 8.56 (s, 1H, NH).
13C NMR (62.5 MHz, CDCl3): d = 34.27 (1C, CH2, C-2), 68.70 (1C,
CH2, C-6), 71.43, 73.28, 74.63 (3C, CH2, OCH2Ph), 75.91, 76.49–
77.50, 78.15 (3C, CH, C-3, C-4, C-5), 96.10 (1C, CH, C-1), 127.57–
128.92 (15C, CH, Ph-CH), 138.03–160.88 (5C, Cipso).
3,4-Di-O-benzyl-2-deoxy-a/b-L-fucopyranosyl Fluoride (5)
Pale red oil; quantitative yield; anomeric ratio a/b = 13.6:1; Rf:0.66
(EtOAc/hexane 1/2).
MS (EI): m/z = 330 [M+]. C20H23O3F.
a-Anomer:
1H NMR (500 MHz, CDCl3): d = 1.22 (d, J5,6 = 6.5 Hz, 3H, 6-CH3),
2.15–2.19 (m, 1H, 2’-H), 2.25–2.30 (m, 1H, 2-H), 3.67 (s, 1H, 4-H),
3.91–3.95 (m, 1H, 3-H), 4.02 (q, J5,6 = 6.5 Hz, 1H, 5-H), 4.59–4.62
(m, 2H, OCH2Ph), 4.69 (d, Jgem = 11.6 Hz, 1H, OCH2Ph), 4.98 (d,
J
gem = 11.6 Hz, 1H, OCH2Ph), 5.77 (d, J1,F = 52.7 Hz, 1H, 1-H),
3,4,6-Tri-O-benzyl-2-deoxy-a-D-glucopyranosyl Trichloroace-
timidate (1)
Pale yellow oil; yield quantitative; anomeric ratio = 25:1; Rf:0.24
(EtOAc/hexane 1/2). C29H30NCl3O5.
7.25–7.39 (m, 10H, Ph-H).
13C NMR (125.7 MHz, CDCl3): d = 17.15 (1C, CH3, C-6), 30.30 (d,
JC2,F = 26.0 Hz, 1C, C-2), 69.58 (1C, CH, C-5), 70.50 (1C, CH2,
OCH2Ph), 74.09 (1C, CH, C-3), 74.44 (1C, CH2, OCH2Ph), 75.08
(1C, CH, C-4), 107.77 (d, JC1,F = 213.8 Hz, 1C, C-1), 127.33–
128.76 (10C, CH, Ph-CH), 138.21, 138.53 (2C, Cipso).
1H NMR(500 MHz, CDCl3): d = 1.85 (ddd, J1,2 = 3.2 Hz,
J2,3 = J2,2’ = 12.6 Hz, 1H, 2-H), 2.38 (dd, J2’,3 = 4.4 Hz, J2,2’ = 13.6
Hz, 1H, 2’-H), 3.54 (t, J4,3 = J4,5 = 9.4 Hz, 1H, 4-H), 3.59–3.65 (m,
2H, 6’-H, 6-H), 3.87–3.90 (m, 1H, 5-H), 3.97–4.02 (m, 1H, 3-H),
4.49–4.52 (m, 3H, OCH2Ph), 4.64–4.68 (m, 2H, OCH2Ph), 4.85 (d,
Jgem = 10.9 Hz, 1H, OCH2Ph), 6.24 (s, 1H, 1-H), 7.12–7.34 (m, 15H,
Ph-H), 8.52 (s, 1H, NH).
13C NMR(125.7 MHz, CDCl3): d = 34.03 (1C, CH2, C-2), 68.23
(1C, CH2, C-6), 72.03 (1C, CH2, OCH2Ph), 73.28 (1C, CH, C-5),
73.35, 75.11 (2C, CH2, OCH2Ph), 76.20 (1C, CH, C-3), 77.37 (1C,
CH, C-4), 96.08 (1C, CH, C-1), 96.49 (1C, Cipso), 127.59–128.46
(15C, CH, Ph-CH), 137.17–137.96 (4C, Cipso).
Characteristic signals for the b-anomer:
1H NMR (500 MHz, CDCl3): d = 1.29 (d, J5,6 = 6.4 Hz, 3H, 6-CH3),
5.25 (ddd, J1,F = 52.7 Hz, 1H, 1-H).
3,4-Di-O-benzyl-2,6-dideoxy-a/b-D-ribohexopyranosylFluoride
(6)
Pale yellow oil; yield quantitative; anomeric ratio a:b = 1.1:1;
Rf:0.61 (EtOAc/hexane 1/2).
1H NMR (500 MHz, CDCl3): d = 1.32 (t, J5,6 = 6.9 Hz, 6H, 6a-CH3,
6b-CH3), 1.65 (ddt, J1,2 = J2,3 = 3.4 Hz, J2’,2 = 15.4 Hz, J2,F = 39.6
Hz, 1H, 2a-H), 1.83–1.89 (m, 1H, 2b-H), 2.30–2.39 (m, 1H, 2’b-H),
2.44 (ddd, J2’,3 = 3.1 Hz, J2’,2 = 15.4 Hz, J2’,F = 4.9 Hz, 1H, 2’a-H),
3.16 (dd, J3,4 = 2.8 Hz, J4,5 = 9.6 Hz, 1H, 4a-H), 3.40 (dd, J3,4 = 2.6
Synthesis 1999, No. SI, 1411–1422 ISSN 0039-7881 © Thieme Stuttgart · New York

1416
H. Schene, H. Waldmann
PAPER
Hz, J4,5 = 5.8 Hz, 1H, 4b-H), 3.95 (q, J2’,3 = J2,3 = J3,4 = 2.9 Hz, 1H,
3a-H), 4.04 (q, J2’,3 = J2,3 = J3,4 = 3.8 Hz, 1H, 3b-H), 4.21–4.26 (m,
1H, 5b-H), 4.43 (d, Jgem = 11.9 Hz, 1H, OCH2Ph), 4.49–4.52 (m,
1H, 5a-H), 4.55–4.62 (m, 5H, OCH2Ph), 4.66 (d, Jgem = 12.0 Hz,
1H, OCH2Ph), 4.77 (d, Jgem = 12.4 Hz, 1H, OCH2Ph), 5.57 (dd,
J1,2 = 3.2 Hz, J1,F = 52.5 Hz, 1H, 1a-H), 5.73 (ddd, J1,2’ = 2.6 Hz,
OCH2CH=CH2), 133.84 (1C, CH, OCH2CH=CH2), 170.01 (1C, Cip-
so), 170.68 (1C, Cipso).
Allyl 3,4-Di-O-acetyl-2,6-dideoxy-a/b-D-ribohexopyranoside
(28)
This compound was purified by flash chromatography with EtOAc/
hexane (1% Et3N) 1/8. Yield 81%; anomeric ratio a:b = 1.1:1.
C13H20O6•0.25 H2O calcd C 56.41, H 7.46; found C 56.68, H 6.93.
J1,2 = 5.6 Hz, J1,F = 53.6 Hz, 1H, 1b-H), 7.25–7.40 (m, 20H, Ph-H).
13C NMR (125.7 MHz, CDCl3): d = 17.98 (1C, CH3, C-6a), 19.30
(1C, CH3, C-6b), 32.02 (d, JC2,F = 25.6 Hz, 1C, CH2, C-2a), 33.05
(d, JC2,F = 23.5 Hz, 1C, CH2, C-2b), 65.30 (1C, CH, C-5a), 68.36
(1C, CH, C-3a), 69.85 (d, JC3,F = 6.1 Hz, 1C, CH, C-3b), 70.81,
70.83, 71.25, 71.88 (4C, CH2, OCH2Ph), 71.88 (1C, CH, C-5b),
78.01 (1C, CH, C-4b), 79.44 (1C, CH, C-4a), 105.3 (d, JC1,F = 220.8
Hz, 1C, CH, C-1a), 107.68 (d, JC1,F = 209.1 Hz, 1C, CH, C-1b),
127.55–128.43 (20C, CH, Ph-CH), 137.91, 138.06, 138.18, 138.42
(4C, Cipso).
b-Anomer: white solid; mp 24 °C; Rf:0.60 (EtOAc/hexane 1/1);
[a]21D = +4.2 (c = 1.1 in CHCl3).
1H NMR (500 MHz, CDCl3): d = 1.23 (d, J5,6 = 6.3 Hz, 3H, 6-CH3),
1.89 (ddd, J2,3 = 3.0 Hz, J2,1 = 9.2 Hz, J2’,2 = 14.2 Hz, 1H, 2-H), 2.01
(s, 3H, C(O)CH3), 2.06 (ddd, J2’,1 = 2.3 Hz, J2’,3 = 4.2 Hz, J2’,2 = 14.2
Hz, 1H, 2’-H), 2.10 (s, 3H, C(O)CH3), 3.91–3.97 (m, 1H, 5-H), 4.06
(ddt, 4J = 1.2 Hz, Jvic = 6.2 Hz, Jgem = 12.7 Hz, 1H, OCH2CH=CH2),
4.37 (ddt, 4J = 1.4 Hz, Jvic = 5.2 Hz, Jgem = 12.7 Hz, 1H,
OCH2CH=CH2), 4.60 (dd, J3,4 = 3.1 Hz, J4,5 = 9.5 Hz, 1H, 4-H),
4.84 (dd, J1,2’ = 2.2 Hz, J1,2 = 9.2 Hz 1H, 1-H), 5.19 (dd, Jgem = 1.4
Hz, Jcis = 10.4 Hz, 1H, OCH2CH=CH2), 5.29 (ddt, Jgem = 1.6 Hz,
MS (EI): m/z = 330 [M+]. C20H23O3F.
Allyl Glycosides 27 and 28; General Procedure
J
J
trans = 17.2 Hz, 1H, OCH2CH=CH2), 5.45 (ddd, J3,4 = J3,2’ = 3.2 Hz,
3,2 = 3.7 Hz 1H, 3-H), 5.88–5.96 (m, 1H, OCH2CH=CH2).
1,3,4-Tri-O-acetyl-2-deoxy-a/b-L-fucopyranose20 (25) or 1,3,4-tri-
O-acetyl-2-deoxy-a/b-D-ribohexopyranose19 (26) were dissolved in
allyl alcohol (4.1 mL) and sat. HCl in Et2O (0.7 mL) was added at
0 °C under Ar. After 2 h stirring K2CO3 was added, the mixture was
filtered through Celite and the allyl alcohol was removed in vacuo.
In the case of digitoxose a few drops of Et3N had to be added before
removal of the alcohol. The crude product was purified by flash
chromatography using hexane/Et2O 6/1 as eluent.
13C NMR (125.7 MHz, CDCl3): d = 17.81 (1C, CH3, C-6), 20.68
(1C, C(O)CH3), 20.88 (1C, C(O)CH3), 35.45 (1C, CH2, C-2), 67.21
(1C, CH, C-5), 68.05 (1C, CH, C-3), 69.57 (1C, CH2,
OCH2CH=CH2), 72.5 (1C, CH, C-4), 97.07 (1C, CH, C-1), 117.25
(1C, CH2, OCH2CH=CH2), 133.97 (1C, CH, OCH2CH=CH2),
169.85 (1C, Cipso), 169.88 (1C, Cipso).
a-Anomer: colorless oil; Rf:0.41 (EtOAc/hexane 1/2);
[a]21D = +187.2 (c = 0.5; in CHCl3).
Allyl 3,4-Di-O-acetyl-2-deoxya/b-L-fucopyranoside (27)
Yield 76%; anomeric ratio a:b = 1.6:1.
1H NMR (500 MHz, CDCl3): d = 1.18 (d, J5,6 = 6.4 Hz, 3H, 6-CH3),
1.99–2.10 (m, 1H, 2-H), 2.04 (s, 3H, C(O)CH3), 2.09 (s, 3H,
C(O)CH3), 2.17 (ddd, J2’,1 = 1.4 Hz, J2’,3 = 3.7 Hz, J2’,2 = 15.05 Hz,
1H, 2’-H), 3.94 (ddt, 4J = 1.4 Hz, Jvic = 5.7 Hz, Jgem = 13.4 Hz, 1H,
OCH2CH=CH2), 4.19–4.28 (m, 2H, 5-H, OCH2CH=CH2), 4.65 (dd,
C13H20O6 calcd C 57.34, H 7.40; found C 57.57, H 7.06.
a-Anomer: colorless oil; Rf:0.11 (hexane/Et2O 3/1); [a]22D = –145.5
(c = 0.8 in MeOH).
1H NMR (500 MHz, CDCl3): d = 1.13 (d, J5,6 = 6.6 Hz, 3H, 6-CH3),
1.86 (dd, J2’,3 = 5.1 Hz, J2’,2 = 12.6 Hz, 1H, 2’-H), 1.98 (s, 3H,
C(O)CH3), 2.05 (ddd, J2,1 = 3.7 Hz, J2,3 = J2’,2 = 12.5 Hz, 1H, 2-H),
2.16 (s, 3H, C(O)CH3), 3.97 (ddt, 4J = 1.3 Hz, Jvic = 6.0 Hz,
J3,4 = 3.2 Hz, J4,5 = 9.5 Hz, 1H, 4-H), 4.85 (d, J1,2 = 3.6 Hz, 1H, 1-
H), 5.17 (dd, Jgem = 1.7 Hz, Jcis = 10.5 Hz, 1H, OCH2CH=CH2), 5.26
(q, J3,4 = J3,2’ = J3,2 = 3.5 Hz, 1H, 3-H), 5.33 (ddt, 4J = Jgem = 1.7 Hz,
Jtrans = 17.1 Hz, 1H, OCH2CH=CH2), 5.88–5.96 (m, 1H,
OCH2CH=CH2).
13C NMR (125.7 MHz, CDCl3): d = 17.31 (1C, CH3, C-6), 20.80
(1C, C(O)CH3), 21.15 (1C, C(O)CH3), 33.18 (1C, CH2, C-2), 62.07
(1C, CH, C-5), 66.42 (1C, CH, C-3), 67.86 (1C, CH2,
OCH2CH=CH2), 72.32 (1C, CH, C-4), 95.01 (1C, CH, C-1), 116.17
(1C, CH2, OCH2CH=CH2), 134.37 (1C, CH, OCH2CH=CH2),
169.98 (1C, Cipso), 170.68 (1C, Cipso).
J
gem = 13.0 Hz, 1H, OCH2CH=CH2), 4.08 (q, J5,6 = 6.6 Hz, 1H, 5-
H), 4.14 (ddt, 4J = 1.4 Hz, Jvic = 5.2 Hz, Jgem = 13.0 Hz, 1H,
OCH2CH=CH2), 5.02 (d, J1,2 = 3.3 Hz, 1H, 1-H), 5.18–5.20 (m, 2H,
4-H, OCH2CH=CH2), 5.27–5.33 (m, 2H, 3-H, OCH2CH=CH2),
5.86–5.94 (m, 1H, OCH2CH=CH2).
13C NMR(125.7 MHz, CDCl3): d = 16.43 (1C, CH3, C-6), 20.67
(1C, C(O)CH3), 20.84 (1C, C(O)CH3), 29.82 (1C, CH2, C-2), 64.63
(1C, CH, C-5), 66.74 (1C, CH, C-3), 69.97 (1C, CH2,
OCH2CH=CH2), 69.78 (1C, CH, C-4), 96.57 (1C, CH, C-1), 117.11
(1C, CH2, OCH2CH=CH2), 133.95 (1C, CH, OCH2CH=CH2),
169.99 (1C, Cipso), 170.63 (1C, Cipso).
Deacetylation of 27 and 28; General Procedure
To a solution of allyl 3,4-di-O-acetyl-2-deoxy-a-L-fucopyranoside
(27a) allyl 3,4-di-O-acetyl-2-deoxy-b-L-fucopyranoside (27b) allyl
3,4-di-O-acetyl-2,6-dideoxy-a-D-ribo-hexopyranoside (28a) or al-
lyl 3,4-di-O-acetyl-2,6-dideoxy-b-D-ribohexopyranoside (28b) in
MeOH (1.4 mL) was added 1 M NaOCH3/MeOH (1.4 mL) under Ar
at r.t. After stirring for 12 h the solution was neutralized with Am-
berlite 120 H+, filtered and concentrated in vacuo. In the case of 28a
or 28b the reaction went to completion within 1 h.
b-Anomer: colorless oil; Rf = 0.07 (hexane/Et2O 3/1); [a]22D = –9.9
(c = 0.6 in MeOH).
1H NMR (500 MHz, CDCl3): d = 1.22 (d, J5,6 = 6.5 Hz, 3H, 6-CH3),
1.98–1.91 (m, 2H, 2’-H, 2-H), 2.00 (s, 3H, C(O)CH3), 2.16 (s, 3H,
C(O)CH3), 3.68 (dq, J4,5 = 0.9 Hz, J5,6 = 6.5 Hz, 1H, 5-H), 4.09 (ddt,
4J = 1.3 Hz, Jvic = 6.4 Hz, Jgem = 12.3 Hz, 1H, OCH2CH=CH2), 4.40
(ddt, 4J = 1.5 Hz, Jvic = 5.1 Hz, Jgem = 12.8 Hz, 1H, OCH2CH=CH2),
4.57 (dd, J1,2’ = 2.8 Hz, J1,2 = 9.2 Hz, 1H, 1-H), 4.97–5.00 (m, 1H,
3-H), 5.10 (d, J3,4 = 3.1 Hz, 1H, 4-H) 5.19 (ddt, 4J = 1.3 Hz,
Jgem = 1.4 Hz, Jcis = 10.4 Hz, 1H, OCH2CH=CH2), 5.28 (ddt,
4J = Jgem = 1.6 Hz, Jtrans = 18.0 Hz, 1H, OCH2CH=CH2), 5.89–5.96
(m, 1H, OCH2CH=CH2).
13C NMR (125.7 MHz, CDCl3): d = 16.39 (1C, CH3, C-6), 20.67
(1C, C(O)CH3), 20.76 (1C, C(O)CH3), 31.63 (1C, CH2, C-2), 68.61
(1C, CH, C-4), 68.94 (1C, CH, C-3), 69.12 (1C, CH, C-5), 69.67
(1C, CH2, OCH2CH=CH2), 98.62 (1C, CH, C-1), 117.47 (1C, CH2,
Allyl 2-Deoxy-a-L-fucopyranoside (29a)
Colorless oil; quantitative yield; Rf = 0.13 (EtOAc/hexane 2/1);
[a]23D = –176.0 (c = 0.6 in MeOH).
1H NMR (400 MHz, CDCl3): d = 1.21 (d, J5,6 = 6.6 Hz, 3H, 6-CH3),
1.75 (dd, J2’,3 = 5.0 Hz, J2’,2 = 10.2 Hz, 1H, 2’-H), 1.91 (ddd,
J2,1 = 3.7 Hz, J2,3 = J2’,2 = 12.4 Hz, 1H, 2-H), 3.56 (d, J3,4 = 2.1 Hz,
1H, 4-H), 3.85 (q, J5,6 = 6.5 Hz, 1H, 5-H), 3.91–3.99 (m, 2H, 3-H,
OCH2CH=CH2), 4.10 (dd, Jvic = 5.1 Hz, Jgem = 13.2 Hz, 1H,
OCH2CH=CH2), 4.89 (d, J1,2 = 3.1 Hz, 1H, 1-H), 5.14 (dd,
4J = Jgem = 1.2 Hz, Jcis = 10.4 Hz, 1H, OCH2CH=CH2), 5.26 (dd,
Synthesis 1999, No. SI, 1411–1422 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of Deoxy Glycosides Under Neutral Conditions in LiClO4/Solvent Mixtures
1417
4J = Jgem = 1.6 Hz, Jtrans = 17.4 Hz, 1H, OCH2CH=CH2), 5.87–5.96
(m, 1H, OCH2CH=CH2).
13C NMR (100.6 MHz, CDCl3): d = 17.16 (1C, CH3, C-6), 33.02
(1C, CH2, C-2), 66.58, 67.28, 71.92 (3C, CH, C-3, C-4, C-5), 68.57
(1C, CH2, OCH2CH=CH2), 97.99 (1C, CH, C-1), 116.77 (1C, CH2,
OCH2CH=CH2), 135.68 (1C, CH, OCH2CH=CH2).
C-3), 75.76 (1C, CH, C-4), 97.12 (1C, CH, C-1), 116.74 (1C, CH2,
OCH2CH=CH2), 127.22–128.36 (10C, CH, Ph-CH), 134.46 (1C,
CH, OCH2CH=CH2), 138.64 (1C, Cipso), 138.89 (1C, Cipso).
C23H28O4 calcd C 74.97, H 7.66; found C 75.11, H 7.12.
Allyl 3,4-Di-O-benzyl-2-deoxy-b-L-fucopyranoside (31b)
Colorless oil; yield 71%; Rf:0.54 (EtOAc/hexane 1/2);
[a]21D = +49.0 (c = 0.6 in CHCl3).
1H NMR(500 MHz, CDCl3): d = 1.21 (d, J5,6 = 6.4 Hz, 3H, 6-CH3),
2.06–2.10 (m, 2H, 2’-H, 2-H), 3.35 (q, J5,6 = 6.4 Hz, 1H, 5-H), 3.50
(s, 1H, 4-H), 3.51–3.55 (m, 1H, 3-H), 4.02 (dd, Jvic = 6.4 Hz,
Jgem = 12.8 Hz, 1H, OCH2CH=CH2), 4.36 (ddt, 4J = 1.4 Hz,
C9H16O4•0.25 H2O calcd C 56.09, H 8.63; found C 56.31, H 8.47.
Allyl 2-Deoxy-b-L-fucopyranoside (29b)
Colorless oil; quantitative yield; Rf = 0.13 (EtOAc/hexane 2/1);
[a]23D = +41.8 (c = 0.5 in MeOH).
1H NMR (400 MHz, CDCl3): d = 1.27 (d, J5,6 = 6.5 Hz, 3H, 6-CH3),
1.75–1.70 (m, 1H, 2’-H), 1.82–1.89 (m, 1H, 2-H), 3.47–3.52 (m,
2H, 4-H, 5-H), 3.68–3.73 (m, 1H, 3-H), 4.05 (dd, Jvic = 5.9 Hz,
Jvic = 5.0 Hz, Jgem = 12.8 Hz, 1H, OCH2CH=CH2), 4.41 (dd,
J1,2’ = 3.5 Hz, J1,2 = 8.6 Hz, 1H, 1-H), 4.58 (q, Jgem = 12.2 Hz, 2H,
OCH2Ph), 4.71 (d, Jgem = 11.9 Hz, 1H, OCH2Ph), 4.96 (d,
Jgem = 13.0 Hz, 1H, OCH2CH=CH2), 4.31 (dd, Jvic = 5.1 Hz,
J
gem = 11.9 Hz, 1H, OCH2Ph), 5.15 (dd, Jgem = 1.3 Hz, Jcis = 10.4 Hz,
1H, OCH2CH=CH2), 5.26 (ddt, 4J = 1.5 Hz, Jgem = 3.1 Hz,
trans = 17.3 Hz, 1H, OCH2CH=CH2), 5.87–5.95 (m, 1H,
Jgem = 13.0 Hz, 1H, OCH2CH=CH2), 4.48 (dd, J1,2’ = 2.2 Hz,
4
J
1,2 = 9.7 Hz, 1H, 1-H), 5.14 (dd, J = Jgem = 1.5 Hz, Jcis = 10.4 Hz,
J
4
1H, OCH2CH=CH2), 5.26 (dd, J = Jgem = 1.7 Hz, Jtrans = 17.3 Hz,
1H, OCH2CH=CH2), 5.87–5.97 (m, 1H, OCH2CH=CH2).
OCH2CH=CH2), 7.23–7.40 (m, 10H, Ph-H).
13C NMR(125.7 MHz, CDCl3): d = 17.22 (1C, CH3, C-6), 32.31
(1C, CH2, C-2), 69.28 (1C, CH2, OCH2CH=CH2), 70.19 (1C, CH2,
OCH2Ph), 70.79 (1C, CH, C-5), 74.20 (1C, CH2, OCH2Ph), 74.34
(1C, CH, C-4), 77.91 (1C, CH, C-3), 99.13 (1C, CH, C-1), 117.13
(1C, CH2, OCH2CH=CH2), 127.28–128.48 (10C, CH, Ph-CH),
134.41 (1C, CH, OCH2CH=CH2), 138.39 (1C, Cipso), 138.86 (1C,
13C NMR (100.6 MHz, CDCl3): d = 16.93 (1C, CH3, C-6), 35.05
(1C, CH2, C-2), 69.67 (1C, CH, C-3), 70.19 (1C, CH2,
OCH2CH=CH2), 71.01 (1C, CH, C-4), 71.68 (1C, CH, C-5), 100.41
(1C, CH, C-1), 116.85 (1C, CH2, OCH2CH=CH2), 135.61 (1C, CH,
OCH2CH=CH2). C9H16O4•0.25 H2O calcd C 56.09, H 8.63; found C
56.31, H 8.47.
Cipso).
C23H28O4 calcd C 74.97, H 7.66; found C 75.11, H 7.12.
Allyl 2,6-Dideoxy-a/b-D-ribohexopyranoside (30)
This compound used directly in the next protection step without fur-
ther characterization.
Allyl 3,4-Di-O-benzyl-2,6-dideoxy-a/b-D-ribohexopyranoside
(32)
The crude product was purified by flash chromatography with
EtOAc/hexane (1% Et3N) 1/8.
b-Anomer: quantitative yield; colorless oil; Rf:0.16 (EtOAc/hexane
1/1), [a]21D = –39.2 (c = 0.7 in MeOH).
b-Anomer: yield 89%; colorless oil; Rf:0.23 (EtOAc/hexane 1/8);
[a]22D = +53.7 (c = 0.5 in CHCl3).
a-Anomer: yield 71%; colorless oil; Rf:0.11 (EtOAc/hexane 1/2);
[a]21D = +153.6 (c = 0.6 in methanol).
1H NMR (400 MHz, CDCl3): d = 1.31 (d, J5,6 = 6.3 Hz, 3H, 6-CH3),
1.56 (ddd, J2,3 = 2.5 Hz, J2,1 = 9.6 Hz, J2’,2 = 13.7 Hz, 1H, 2-H), 2.21
(ddd, J1,2’ = 2.1 Hz, J2’,3 = 3.8 Hz, J2’,2 = 13.8 Hz, 1H, 2’-H), 3.11
(dd, J3,4 = 2.8 Hz, J4,5 = 9.2 Hz, 1H, 4-H), 3.95 (q,
Protection of 29 and 30 as Benzyl Ethers; General Procedure
A solution of allyl 2-deoxy-a-L-fucopyranoside (29a), allyl 2-
deoxy-b-L-fucopyranoside (29b), allyl-2,6-dideoxy-a-D-ribohex-
opyranoside (30a), or allyl-2,6-dideoxy-b-D-ribohexopyranoside
(30b) in DMF (68 mL) was treated in three portions with NaH (25.2
mmol) and stirred for 30 min at 0 °C. A solution of benzyl chloride
(48.6 mmol) in DMF (12 mL) was added within 1 h. After stirring
for 12 h at r.t. MeOH (2 mL) was added at 0 °C. In the case of 30a
or 30b the reaction was complete within 1.5 h at 0 °C. After the sol-
vent was removed in vacuo the residue was taken up in CH2Cl2 (50
mL) and the solution was extracted with water. The organic phase
was dried (MgSO4), the solvent was removed in vacuo and the prod-
uct was isolated by flash chromatography using EtOAc/hexane 1/8
as eluent.
J
3,2 = J3,2’ = J3,4 = 2.9 Hz, 1H, 3-H), 3.98–4.06 (m, 2H, 5-H,
OCH2CH=CH2), 4.31–4.34 (m, 1H, OCH2CH=CH2), 4.38 (d,
gem = 11.8 Hz, 1H, OCH2Ph), 4.52 (d, Jgem = 11.7 Hz, 1H,
OCH2Ph), 4.59–4.67 (2d, Jgem = 12.2 Hz, 2H, OCH2Ph), 4.87 (dd,
J
4
J
J
1,2’ = 1.9 Hz, J1,2 = 9.5 Hz, 1H, 1-H), 5.14 (dd, J = Jgem = 1.4 Hz,
4
cis = 10.9 Hz, 1H, OCH2CH=CH2), 5.25 (ddt, J = Jgem = 1.6 Hz,
Jtrans = 17.2 Hz, 1H, OCH2CH=CH2), 5.58–5.95 (m, 1H,
OCH2CH=CH2), 7.22–7.35 (m, 10H, Ph-H).
13C NMR (125.7 MHz, CDCl3): d = 18.55 (1C, CH3, C-6), 35.37
(1C, CH2, C-2), 69.15 (1C, CH, C-5), 69.71 (1C, CH2,
OCH2CH=CH2), 71.13 (1C, CH, C-3), 71.39, 71.62 (2C, CH2,
OCH2Ph), 80.93 (1C, CH, C-4), 97.34 (1C, CH, C-1), 117.15 (1C,
CH2, OCH2CH=CH2), 127.69–128.44 (10C, CH, Ph-CH), 134.48
(1C, CH, OCH2CH=CH2), 138.15 (1C, Cipso), 138.69 (1C, Cipso).
Allyl 3,4-Di-O-benzyl-2-deoxy-a-L-fucopyranoside (31a)
Colorless oil; yield 80%; Rf:0.57 (EtOAc/hexane 1/2),[a]21D = –80.0
(c = 0.6 in CHCl3).
1H NMR (500 MHz, CDCl3): d = 1.17 (d, J5,6 = 6.5 Hz, 3H, 6-CH3),
C23H28O4 calcd C 74.97, H 7.66; found C 74.92, H 7.63.
2.00 (dd, J2’,3 = 4.6 Hz, J2’,2 = 12.6 Hz, 1H, 2’-H), 2.20 (ddd,
a-Anomer: yield 77%; colorless oil; Rf:0.31 (EtOAc/hexane 1/4);
[a]20D = +162.3 (c = 0.5 in CHCl3).
1H NMR (500 MHz, CDCl3): d = 1.26 (d, J5,6 = 6.4 Hz, 3H, 6-CH3),
1.66 (dt, J2,3 = J2,1 = 3.5 Hz, J2’,2 = 14.8 Hz, 1H, 2-H), 2.32 (ddd,
J1,2’ = 1.3 Hz, J2’,3 = 3.6 Hz, J2’,2 = 14.8 Hz, 1H, 2’-H), 3.14 (dd,
J2,1 = 3.7 Hz, J2,3 = J2’,2 = 12.3 Hz, 1H, 2-H), 3.60 (s, 1H, 4-H), 3.81
(q, J5,6 = 6.5 Hz, 1H, 5-H), 3.90–3.96 (m, 2H, 3-H, OCH2CH=CH2),
4.09 (dd, Jvic = 5.2 Hz, Jgem = 13.1 Hz, 1H, OCH2CH=CH2), 4.56–
4.62 (m, 2H, OCH2Ph), 4.68 (d, Jgem = 11.7 Hz, 1H, OCH2Ph), 4.96
(d, Jgem = 11.7 Hz, 1H, OCH2Ph), 4.99 (d, J1,2 = 3.5 Hz, 1H, 1-H),
5.14 (d, Jcis = 10.4 Hz, 1H, OCH2CH=CH2), 5.25 (dd, 4J = Jgem = 1.5
Hz, Jtrans = 17.2 Hz, 1H, OCH2CH=CH2), 5.85–5.92 (m, 1H,
OCH2CH=CH2), 7.22–7.39 (m, 10H, Ph-H).
13C NMR (125.7 MHz, CDCl3): d = 17.27 (1C, CH3, C-6), 30.61
(1C, CH2, C-2), 66.72 (1C, CH, C-5), 67.77 (1C, CH2,
OCH2CH=CH2), 70.36, 74.31 (2C, CH2, OCH2Ph), 75.34 (1C, CH,
J3,4 = 3.0 Hz, J4,5 = 9.0 Hz, 1H, 4-H), 3.90–3.95 (m, 2H, 3-H,
OCH2CH=CH2), 4.20–4.24 (m, 1H, OCH2CH=CH2), 4.30–4.35 (m,
1H, 5-H), 4.40 (d, Jgem = 12.0 Hz, 1H, OCH2Ph), 4.54–4.60 (2d,
J
gem = 12.0 Hz, 2H, OCH2Ph), 4.77–4.81 (m, 2H, 1-H, OCH2Ph),
5.13 (dd, Jgem = 1.5 Hz, Jcis = 8.2 Hz, 1H, OCH2CH=CH2), 5.31 (dd,
gem = 1.7 Hz, Jtrans = 17.2 Hz, 1H, OCH2CH=CH2), 5.88–5.96 (m,
1H, OCH2CH=CH2), 7.23–7.41 (m, 10H, Ph-H).
J
Synthesis 1999, No. SI, 1411–1422 ISSN 0039-7881 © Thieme Stuttgart · New York

1418
H. Schene, H. Waldmann
PAPER
13C NMR (125.7 MHz, CDCl3): d = 18.06 (1C, CH3, C-6), 31.67
(1C, CH2, C-2), 63.42 (1C, CH, C-5), 67.83 (1C, CH2,
OCH2CH=CH2), 68.95 (1C, CH, C-3), 70.11, 70.51 (2C, CH2,
OCH2Ph), 79.85 (1C, CH, C-4), 95.46 (1C, CH, C-1), 116.14 (1C,
CH2, OCH2CH=CH2), 127.38–128.28 (10C, CH, Ph-CH), 134.71
(1C, CH, OCH2CH=CH2), 138.32 (1C, Cipso), 138.75 (1C, Cipso).
OCH=CHCH3 Z), 103.56 (1C, CH, OCH=CHCH3 E), 127.36–
128.54 (20C, CH, Ph-CH), 138.35 (2C, Cipso), 138.90 (2C, Cipso),
142.70 (1C, CH, OCH=CHCH3 Z), 143.80 (1C, CH, OCH=CHCH3
E).
C23H28O4.
Prop-1-enyl 3,4-Di-O-benzyl-2,6-dideoxy-a/b-D-ribohexopyra-
noside (34)
The crude compound was purified by flash chromatography with
EtOAc/hexane 1/10 as eluent.
Isomerization of Allyl Glycosides to Propenyl Glycosides; Gen-
eral Procedure
A suspension of allyl glycoside 31 or 32 (1 mmol), (PPh3)3RhCl
(0.1 mmol) and 1,4-diazabicyclo[2.2.2]octane (0.3 mmol) in EtOH/
H2O (10/1) (23.3 mL) was stirred for 25 min at 85 °C. The solvent
was distilled off in vacuo and the residue was filtered through a
short silica gel column with EtOAc/hexane 1/10 as eluent to remove
the catalyst.
b-Anomer: Yield 93%; E/Z-ratio:1/1.5; colorless oil; Rf:0.63
(EtOAc/hexane 1/2).
1H NMR (500 MHz, CDCl3): d = 1.30 (d, J5,6 = 6.2 Hz, 6H, 6-CH3
E, 6-CH3 Z), 1.53 (dd, 4J = 1.4 Hz, Jvic = 6.8 Hz, 3H, OCH=CHCH3
E), 1.58 (dd, 4J = 1.6 Hz, Jvic = 6.8 Hz, 3H, OCH=CHCH3 Z), 1.61–
1.69 (m, 2H, 2-H E, 2-H Z), 2.22–2.31 (m, 2H, 2’-H E, 2’-H Z), 3.15
(2dd, J3,4 = 2.7 Hz, J4,5 = 9.4 Hz, 2H, 4-H E, 4-H Z), 3.97–4.01 (m,
2H, 3-H E, 3-H Z), 4.05–4.10 (m, 2H, 5-H E, 5-H Z), 4.42 (d,
Jgem = 11.7 Hz, 2H, OCH2Ph), 4.46–4.50 (m, 2H, OCH=CHCH3 Z,
OCH=CHCH3 E), 4.54–4.57 (m, 2H, OCH2Ph), 4.62–4.69 (m, 4H,
OCH2Ph), 5.04–5.08 (m, 2H, 1-H E, 1-H Z), 6.18 (td, 4J = 0.8 Hz,
Prop-1-enyl 3,4-Di-O-benzyl-2-deoxy-a-L-fucopyranoside (33a)
Colorless oil; yield 90%; E/Z-ratio:1/1.8; Rf:0.38 (EtOAc/hexane 1/
2).
1H NMR (500 MHz, CDCl3): d = 1.15, 1.16 (2d, J5,6 = 6.5 Hz, 6H,
6-CH3), 1.53 (dd, 4J = 1.5 Hz, Jvic = 6.1 Hz, 3H, OCH=CHCH3 E),
4
1.56 (dd, J = 1.7 Hz, Jvic = 6.0 Hz, 3H, OCH=CHCH3 Z), 2.00–
J
cis = 6.3 Hz, 1H, OCH=CHCH3 Z), 6.22 (dd, 4J = 1.4 Hz,
2.08 (m, 2H, 2’-H E, 2’-H Z), 2.17–2.24 (m, 2H, 2-H E, 2-H Z), 3.59
(s, 2H, 4-H E, 4-H Z), 3.78–3.83 (m, 2H, 5-H E, 5-H Z), 3.91–3.99
(m, 2H, 3-H E, 3-H Z), 4.45–4.50 (m, 1H, OCH=CHCH3 Z), 4.55–
4.63 (m, 4H, OCH2Ph), 4.67, 4.68, 4.96, 4.98 (4d, Jgem = 11.7 Hz,
4H, OCH2Ph), 4.99–5.04 (m, 1H, OCH=CHCH3 E), 5.16 (d,
J1,2 = 3.7 Hz, 2H, 1-H E, 1-H Z), 6.13 (dq, 4J = 1.7 Hz, Jcis = 6.3 Hz,
Jtrans = 12.3 Hz, 1H, OCH=CHCH3 E), 7.21–7.36 (m, 20H, Ph-H).
13C NMR (125.7 MHz, CDCl3): d = 9.34 (1C, CH3, OCH=CHCH3
Z), 12.36 (1C, CH3, OCH=CHCH3 E), 18.37 (1C, CH3, C-6 Z),
18.40 (1C, CH3, C-6 E), 34.58 (1C, CH2, C-2 Z), 34.63 (1C, CH2,
C-2 E), 69.52 (1C, CH, C-5 E), 69.63 (1C, CH, C-5 Z), 70.79 (1C,
CH, C-3 Z), 70.85 (1C, CH, C-3 E), 71.41–71.60 (4C, CH2,
OCH2Ph), 80.39 (1C, CH, C-4 Z), 80.49 (1C, CH, C-4 E), 97.41
(1C, CH, C-1 E), 97.93 (1C, CH, C-1 Z), 102.47 (1C, CH,
OCH=CHCH3 Z), 103.22 (1C, CH, OCH=CHCH3 E), 127.64–
128.36 (20C, CH, Ph-CH), 137.96 (2C, Cipso), 138.43 (2C, Cipso),
142.98 (1C, CH, OCH=CHCH3 Z), 144.05 (1C, CH, OCH=CHCH3
E).
4
1H, OCH=CHCH3 Z), 6.19 (dq, J = 1.6 Hz, Jtrans = 12.3 Hz, 1H,
OCH=CHCH3 E), 7.15–7.38 (m, 20H, Ph-H).
13C NMR (125.7 MHz, CDCl3): d = 9.19 (1C, CH3, OCH=CHCH3
Z), 12.49 (1C, CH3, OCH=CHCH3 E), 17.21 (2C, CH3, C-6 E, C-6
Z), 29.96 (1C, CH2, C-2 Z), 30.04 (1C, CH2, C-2 E), 67.30 (1C, CH,
C-5 E), 67.45 (1C, CH, C-5 Z), 70.38–74.39 (4C, CH2, OCH2Ph),
74.92 (1C, CH, C-3 Z), 75.08 (1C, CH, C-3 E), 75.64 (2C, CH, C-4
Z, C-4 E), 97.68 (1C, CH, C-1 E), 98.06 (1C, CH, C-1 Z), 102.57
(1C, CH, OCH=CHCH3 Z), 103.13 (1C, CH, OCH=CHCH3 E),
127.21–128.38 (20C, CH, Ph-CH), 138.47–138.81 (4C, Cipso),
142.11 (1C, CH, OCH=CHCH3 Z), 143.28 (1C, CH, OCH=CHCH3
E).
C23H28O4.
a-Anomer: Yield 49%; E/Z-ratio:1/1; colorless oil; Rf:0.61 (EtOAc/
hexane 1/2).
1H NMR (500 MHz, CDCl3): d = 1.25, 1.26 (2d, J5,6 = 6.4 Hz, 6H,
6-CH3 E, 6-CH3 Z), 1.54–1.70 (m, 8H, 2-H E, 2-H Z, OCH=CHCH3
E, OCH=CHCH3 Z), 2.36 (ddd, J1,2’ = 1.3 Hz, J2’,3 = 3.5 Hz,
J2’,2 = 15.9 Hz, 1H, 2’-H E), 2.42 (ddd, J1,2’ = 1.0 Hz, J2’,3 = 3.3 Hz,
C23H28O4.
Prop-1-enyl 3,4-Di-O-benzyl-2-deoxy-b-L-fucopyranoside (33b)
Colorless oil; yield 76%; E/Z-ratio:1/1; Rf:0.36 (EtOAc/hexane 1/
J2’,2 = 15.0 Hz, 1H, 2’-H Z), 3.12–3.15 (m, 2H, 4-H E, 4-H Z), 3.90–
2).
3.95 (m, 2H, 3-H E, 3-H Z), 4.29–4.36 (m, 2H, 5-H E, 5-H Z), 4.41,
4.42 (2d, Jgem = 12.0 Hz, 2H, OCH2Ph), 4.47–4.61 (m, 5H, 2 x
OCH2Ph, OCH=CHCH3 Z), 4.79, 4.84 (2d, Jgem = 12.3 Hz, 2H,
OCH2Ph), 4.97 (d, J1,2 = 3.7 Hz, 1H, 1-H E), 5.00 (d, J1,2 = 4.0 Hz,
1H, 1-H Z), 5.04–5.12 (m, 1H, OCH=CHCH3 E), 6.12 (dq, 4J = 1.7
Hz, Jcis = 6.2 Hz, 1H, OCH=CHCH3 Z), 6.20 (dt, 4J = 1.5 Hz,
1H NMR (500 MHz, CDCl3): d = 1.23, 1.24 (2d, J5,6 = 6.5 Hz, 6H,
6-CH3), 1.53 (dd, 4J = 1.4 Hz, Jvic = 7.6 Hz, 3H, OCH=CHCH3 E),
4
1.59 (dd, J = 1.6 Hz, Jvic = 6.9 Hz, 3H, OCH=CHCH3 Z), 2.05–
2.18 (m, 4H, 2’-H E, 2’-H Z, 2-H E, 2-H Z), 3.40 (q, J5,6 = 6.4 Hz,,
2H, 5-H E, 5-H Z), 3.50 (s, 2H, 4-H E, 4-H Z), 3.52–3.56 (m, 2H,
3-H E, 3-H Z), 4.44–4.50 (m, 1H, OCH=CHCH3 Z), 4.56–4.63 (m,
6H, 2 x OCH2Ph, 1-H E, 1-H Z), 4.69, 4.72 (2d, Jgem = 11.8 Hz, 2H,
OCH2Ph), 4.96 (d, Jgem = 11.9 Hz, 2H, OCH2Ph), 5.03–5.09 (m, 1H,
OCH=CHCH3 E), 6.18 (dd, 4J = 1.7 Hz, Jcis = 6.3 Hz, 1H,
OCH=CHCH3 Z), 6.23 (dd, 4J = 1.5 Hz, Jtrans = 12.3 Hz, 1H,
OCH=CHCH3 E), 7.21–7.39 (m, 20H, Ph-H).
13C NMR (125.7 MHz, CDCl3): d = 9.48 (1C, CH3, OCH=CHCH3
Z), 12.46 (1C, CH3, OCH=CHCH3 E), 17.26 (1C, CH3, C-6 Z),
17.28 (1C, CH3, C-6 E), 31.77 (1C, CH2, C-2 E), 31.79 (1C, CH2,
C-2 Z), 70.31 (2C, CH2, OCH2Ph), 71.25 (1C, CH, C-5 E), 71.32
(1C, CH, C-5 Z), 74.34–74.41 (4C, 2CH, 2CH2, C-4 Z, C-4 E,
2*OCH2Ph), 77.64 (1C, CH, C-3 E), 77.67 (1C, CH, C-3 Z), 99.47
(1C, CH, C-1 E), 99.98 (1C, CH, C-1 Z), 102.73 (1C, CH,
Jtrans = 10.7 Hz, 1H, OCH=CHCH3 E), 7.21–7.43 (m, 20H, Ph-H).
13C NMR (125.7 MHz, CDCl3): d = 9.46 (1C, CH3, OCH=CHCH3
Z), 12.63 (1C, CH3, OCH=CHCH3 E), 18.08 (2C, CH3, C-6 Z, C-6
E), 30.95 (1C, CH2, C-2 Z), 31.19 (1C, CH2, C-2 E), 63.76 (1C, CH,
C-5 Z), 63.92 (1C, CH, C-5 E), 68.50 (1C, CH, C-3 Z), 68.87 (1C,
CH, C-3 E), 70.09, 70.19, 70.53, 70.55 (4C, CH2, OCH2Ph), 79.67
(1C, CH, C-4 E), 79.71 (1C, CH, C-4 Z), 95.92 (1C, CH, C-1 E),
96.27 (1C, CH, C-1 Z), 102.97 (1C, CH, OCH=CHCH3 Z), 103.34
(1C, CH, OCH=CHCH3 E), 127.45–128.34 (20C, CH, Ph-CH),
138.18, 138.29, 138.60, 138.75 (4C, Cipso), 142.51 (1C, CH,
OCH=CHCH3 Z), 143.67 (1C, CH, OCH=CHCH3 E).
C23H28O4.
Synthesis 1999, No. SI, 1411–1422 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of Deoxy Glycosides Under Neutral Conditions in LiClO4/Solvent Mixtures
1419
Hydrolysis of the Prop-1-enyl Glycosides 33 and 34; General
Procedure
sion was added a solution of the donor (0.1 mmol) in the same sol-
vent (1 mL). In the case of acceptors without TMS group, CsF (0.1
mmol) was used as acid scavenger. After stirring for 3 d (2 d with
the donors 5 and 6) at r.t., the mixture was diluted with CH2Cl2 (50
mL), filtered and washed with H2O. The organic layer was dried
(Na2SO4) and concentrated in vacuo. The crude product was puri-
fied by flash chromatography.
Prop-1-enyl 3,4-di-O-benzyl-2-deoxy-a/b-L-fucopyranoside (33)
or prop-1-enyl 3,4-di-O-benzyl-2-deoxy-a/b-D-ribohexopyrano-
side (34) (1 mmol) and HgCl2 (5.05 mmol) were suspended in ace-
tone/H2O (5/1) (13.0 ml) at r.t. and stirred for 30 min. After removal
of acetone in vacuo the mixture was extracted with CH2Cl2 (50 mL).
The organic layer was dried (MgSO4) and the solvent was removed
in vacuo. The crude product was purified by flash chromatography
with EtOAc/hexane 1/2.
Glycosidations with Phosphite 3 and Trichloracetimidates 1
and 2; General Procedure
To a mixture of donor (0.1 mmol), acceptor (0.2 mmol), molecular
sieves 4Å (70 mg) and metal perchlorate (0.2–2.0 mmol) was added
the respective solvent (2 mL) under Ar. After a reaction time of 3 d
at r.t. the mixture was diluted with CH2Cl2 (50 mL), filtered and
washed with H2O. The organic layer was dried (Na2SO4) and con-
centrated in vacuo. The crude product was purified by flash chroma-
tography.
3,4-Di-O-benzyl-2-deoxy-a/b-L-fucopyranose (35)
White solid; mp 58 °C; yield 73%; anomeric ratio a:b = 2.4:1;
Rf:0.22 (EtOAc/hexane 1/2).
1H NMR (500 MHz, CDCl3): d = 1.16 (d, J5,6 = 6.5 Hz, 3H, 6a-
CH3), 1.24 (d, J5,6 = 6.4 Hz, 3H, 6b-CH3), 1.93–1.97 (m, 2H, 2-H),
2.14–2.19 (m, 2H, 2’-H), 2.94 (t, J1,OH=2.5 Hz, 1H, 1-OH), 3.44 (q,
J5,6 = 6.4 Hz, 1H, 5b-H), 3.51 (s, 1H, 4b-H), 3.53–3.57 (m, 1H, 3b-
H), 3.61 (s, 1H, 4a-H), 3.73 (d, J1,OH=9.12 Hz, 1H, 1-OH), 3.96–3.99
(m, 1H, 3a-H), 4.06 (q, J5,6 = 6.5 Hz, 1H, 5a-H), 4.56–4.71 (m, 7H,
3 x OCH2Ph, 1b-H), 4.96 (d, Jgem = 11.7 Hz, 2H, OCH2Ph), 5.42 (s,
1H, 1a-H), 7.25–7.39 (m, 20H, Ph-H).
3,4,6-Tri-O-benzyl-2-deoxy-a/b-D-glucopyranosyl-N-diphenyl-
methylene Serine Methyl Ester (15)
Colorless oil; yield 57%; anomeric ratio a:b = 2.4:1.
MS (FAB): m/z = 699 [M+]. C44H45O7N.
13C NMR(125.7 MHz, CDCl3): d = 17.21 (1C, CH3, C-6b), 17.36
(1C, CH3, C-6a), 30.52 (1C, CH2, C-2a), 34.48 (1C, CH2, C-2b),
66.89 (1C, CH, C-5a), 71.14 (1C, CH, C-5b), 70.25, 70.43 (2C,
CH2, OCH2Ph), 74.31–74.78 (4C, 2CH2, 2CH, 2*OCH2Ph, C-3a,
C-4b), 75.67 (1C, CH, C-4a), 77.53 (1C, CH, C-3b), 92.64 (1C,
CH, C-1a), 94.75 (1C, CH, C-1b), 127.28–128.48 (20C, CH, Ph-
CH), 138.22–138.74 (4C, Cipso).
a-Anomer: Rf:0.35 (EtOAc/hexane 1/2); [a]21D = +10.8 (c = 0.7 in
CHCl3).
1H NMR (500 MHz, CDCl3): d = 1.67 (ddd, J2,1 = 3.1 Hz,
J2,2’ = J2,3 = 12.2 Hz, 1H, 2-H), 2.22 (dd, J2’,3 = 5.0 Hz, J2’,2 = 12.8
Hz, 1H, 2’-H), 3.58–3.67 (m, 3H, 4-H, 5-H, 6’-H), 3.68 (s, 3H,
COOCH3), 3.73 (dd, J5,6 = 3.4 Hz, J6’,6 = 10.5 Hz, 1H, 6-H), 3.75–
3.86 (m, 1H, b-CH2), 3.87–3.90 (m, 1H, 3-H), 4.11 (dd, Jvic = 4.7
Hz, Jgem = 9.9 Hz, 1H, b-CH2), 4.34 (dd, Jcis = 4.7 Hz, Jtrans = 7.4 Hz,
1H, a-CH), 4.48 (d, Jgem = 12.1 Hz, 1H, OCH2Ph), 4.51 (d,
MS (EI): m/z = 328 [M+].
C20H24O4.
Jgem = 11.0 Hz, 1H, OCH2Ph), 4.61 (q, Jgem = 11.5 Hz, 3H,
3,4-Di-O-benzyl-2,6-dideoxy-a/b-D-ribohexopyranose (36)
This compound was purified by flash chromatography with EtOAc/
hexane 1/8→1/5. Yield 65%; anomeric ratio a/b = 1/1.3; colorless
oil; Rf:0.18 (EtOAc/hexane 1/2).
OCH2Ph), 4.88 (d, Jgem = 11.0 Hz, 1H, OCH2Ph), 4.95 (d, J1,2 = 2.6
Hz, 1H, 1-H), 7.14–7.38 (m, 23H, Ph-H), 7.64 (d, J = 7.5 Hz, 2H,
Ph-H).
13C NMR (125.7 MHz, CDCl3): d = 35.24 (1C, CH2, C-2), 52.20
(1C, CH3, OCH3), 65.47 (1C, CH, a-CH), 68.04 (1C, CH2, b-CH2),
68.72 (1C, CH2, C-6), 70.84 (1C, CH, C-5), 71.58, 73.43, 74.78
(3C, CH2, OCH2Ph), 76.78–77.29 (1C, CH, C-3), 78.11 (1C, CH, C-
4), 97.75 (1C, CH, C-1), 127.48–130.50 (25C, CH, Ph-CH), 135.98,
138.11, 138.59, 138.70, 139.40, 170.56, 172.02 (7C, Cipso).
1H NMR (500 MHz, CDCl3): d = 1.29 (d, J5,6 = 6.3 Hz, 3H, 6b-
CH3), 1.32 (d, J5,6 = 6.2 Hz, 3H, 6a-CH3), 1.48 (ddd, J2,3 = 2.4 Hz,
J
J
2,1 = 9.7 Hz, J2’,2 = 13.8 Hz, 1H, 2b-H), 1.74 (dt, J1,2 = J2,3 = 3.1 Hz,
2’,2 = 14.4 Hz, 1H, 2a-H), 2.18 (dd, J2’,3 = 3.7 Hz, J2’,2 = 14.4 Hz,
1H, 2’a-H), 2.27 (ddd, J2’,1 = 2.1 Hz, J2’,3 = 3.7 Hz, J2’,2 = 13.8 Hz,
1H, 2’b-H), 3.11 (dd, J4,3 = 2.6 Hz, J4,5 = 8.9 Hz, 2H, 4a-H, 4b-H),
3.59 (d, J1b,OH=5.8 Hz, 1H, 1b-OH), 3.97 (q, J2’,3 = J2,3 = J3,4 = 2.9
Hz, 1H, 3b-H), 4.06–4.12 (m, 2H, 3a-H, 5b-H), 4.29–4.34 (m, 1H,
5a-H), 4.40, 4.47 (2d, Jgem = 11.7 Hz, 2H, OCH2Ph), 4.54–4.69 (m,
5H, OCH2Ph), 4.80 (d, Jgem = 11.9 Hz, 1H, OCH2Ph), 5.08 (dd,
b-Anomer: Rf = 0.42 (EtOAc/hexane 1/2); [a]21D = –54.7 (c = 0.2 in
CHCl3).
1H NMR (250 MHz, CDCl3): d = 1.58 (q, J2,2’ = J2,3 = J2,1 = 10.7 Hz,
1H, 2-H), 2.28 (dd, J2’,3 = 5.0 Hz, J2’,2 = 12.8 Hz, 1H, 2’-H), 3.29–
3.38 (m, 1H, 5-H), 3.46–3.74 (m, 4H), 3.71 (s, 3H, COOCH3), 4.07
(d, J = 7.2 Hz, 2H), 4.34–4.70 (m, 7H, 1-H, 2.5 x OCH2Ph), 4.87 (d,
Jgem = 11.5 Hz, 1H, OCH2Ph), 7.15–7.46 (m, 23H, Ph-H), 7.60–7.67
(m, 2H, PhH).
J
1,2 = 3.6 Hz, J1,OH=11.0 Hz, 1H, 1a-H), 5.19 (ddd, J1,2’ = 2.0 Hz,
J1,OH=5.8 Hz, J1,2 = 9.5 Hz, 1H, 1b-H), 5.31 (d, J1a,OH=11.0 Hz 1H,
1a-OH), 7.24–7.36 (m, 20H, Ph-H).
13C NMR(125.7 MHz, CDCl3): d = 18.26 (1C, CH3, C-6a), 18.36
(1C, CH3, C-6b), 34.11 (1C, CH2, C-2a), 36.36 (1C, CH2, C-2b),
62.85 (1C, CH, C-5a), 69.20, 72.43 (2C, CH, C-3a, C-5b), 70.81
(1C, CH, C-3b), 71.29, 71.49, 71.60, 73.08 (4C, CH2, OCH2Ph),
80.57, 80.96 (2C, CH, C-4a, C-4b), 91.79 (1C, CH, C-1a), 92.19
(1C, CH, C-1b), 127.62–128.52 (20C, CH, Ph-CH), 137.49, 137.75,
137.90, 138.40 (4C, Cipso).
Cholesteryl 3,4,6-Tri-O-benzyl-2-deoxy-a/b-D-glucopyranoside
(16)
MS (MALDI): m/z = 826 [M++Na].
C54H74O5•H2O calcd C 78.98, H 9.33; found C 79.15, H 9.00.
a-Anomer: colorless oil; Rf = 0.48 (CH2Cl2/Et2O 20/1);
[a]21D = +65.6 (c = 2.2 in CHCl3).
1H NMR(500 MHz, CDCl3): d = 0.67 (s, 3H), 0.85–0.97 (m, 10H),
0.99–1.22 (m, 11H), 1.22–1.60 (m, 12H), 1.73 (ddd, J2,1 = 3.3 Hz,
MS (EI):328 [M+].
C20H24O4.
J
2,3 = J2,2’ = 12.2 Hz, 1H, 2-H), 1.79–2.02 (m, 5H), 2.24–2.35 (m,
Glycosidation Reactions
Glycosidations with the Fluorides 4, 5 and 6 as Donors; General
Procedure
Pulverized, freshly activated molecular sieves 4Å (70 mg), LiClO4
or Ba(ClO4)2 (0.2 mmol) and acceptor (0.2 mmol) were stirred in
Et2O, CH2Cl2 or MeCN (1 mL) for 30 min under Ar. To this suspen-
3H, 2’-H), 3.43–3.49 (m, 1H), 3.62 (t, J3,4 = J4,5 = 9.4 Hz, 1H, 4-H),
3.68 (dd, J5,6’ = 1.9 Hz, J6’,6 = 10.5 Hz, 1H, 6’-H), 3.80 (dd, J5,6 = 3.9
Hz, J6’,6 = 10.5 Hz, 1H, 6-H), 3.85–3.88 (m, 1H, 5-H), 4.00–4.05
(m, 1H, 3-H), 4.49 (d, Jgem = 12.0 Hz, 1H, OCH2Ph), 4.51 (d,
Jgem = 10.7 Hz, 1H, OCH2Ph), 4.63–4.69 (m, 3H, OCH2Ph), 4.89 (d,
Synthesis 1999, No. SI, 1411–1422 ISSN 0039-7881 © Thieme Stuttgart · New York

1420
H. Schene, H. Waldmann
PAPER
Jgem = 10.7 Hz, 1H, OCH2Ph), 5.13 (d, J1,2 = 2.9 Hz, 1H, 1-H), 5.28
(d, J = 5.0 Hz, 1H), 7.16–7.36 (m, 15H, Ph-H).
6-O-(3,4-Di-O-benzyl-2-deoxy-a/b-L-fucopyranosyl)-1,2:3,4-di-
O-isopropylidene-a-D-galactopyranoside (19)
Yield 75%; anomeric ratio a:b = 13:1.
MS (FAB): m/z = 569 [M+-H]. C32H42O9.
a-Anomer: colorless oil; Rf:0.51 (EtOAc/hexane 1/2); [a]21D = –
16.2 (c = 0.9 in CHCl3).
1H NMR (500 MHz, CDCl3): d = 1.16 (d, J5,6 = 6.5 Hz, 3H, 6b-
CH3), 1.31, 1.34, 1.43, 1.53 (4s, 12H, C(CH3)), 2.03 (dd, J2’,3 = 4.5
Hz, J2’,2 = 12.5 Hz, 1H, 2’b-H), 2.18 (dt, J1,2 = 3.7 Hz,
13C NMR(125.7 MHz, CDCl3): d = 11.85, 18.72, 19.35 (3C, CH3),
21.04 (1C, CH2), 22.57, 22.82 (2C, CH3), 23.82, 24.29, 27.63 (3C,
CH2), 28.01 (1C, CH), 28.23 (1C, CH2), 31.88 (1C, CH), 31.92 (1C,
CH2), 35.78 (1C, CH), 35.91 (1C, Cipso), 36.19, 36.72, 37.07 (3C,
CH2, C-2), 39.51, 39.77, 39.96 (3C, CH2), 42.31 (1C, Cipso), 50.09,
56.14, 56.76 (3C, CH), 68.98 (1C, CH2, C-6), 70.69 (1C, CH, C-5),
71.75, 73.41, 75.01 (3C, CH2, OCH2Ph), 75.87 (1C, CH), 77.84
(1C, CH, C-3), 78.44 (1C, CH, C-4), 95.01 (1C, CH, C-1), 121.64
(1C, CH), 127.46–129.02 (15C, CH, Ph-CH), 138.18, 138.53,
138.82, 140.84 (4C, Cipso).
J
2’,2 = J2,3 = 12.3 Hz, 1H, 2b-H), 3.55 (dd, J6’,5 = 6.7 Hz, J6,6’ = 10.1
Hz, 1H, 6’a-H), 3.59 (s, 1H, 4b-H), 3.77 (dd, J6,5 = 6.4 Hz,
6,6’ = 10.1 Hz, 1H, 6a-H), 3.85–3.94 (m, 3H, 3b-H, 5b-H, 5a-H),
J
b-Anomer:28 colorless solid; mp 109 °C; Rf:0.42 (CH2Cl2/Et2O 20/
4.20 (dd, J5,4 = 1.7 Hz, J4,3 = 7.9 Hz, 1H, 4a-H), 4.31 (dd, J1,2 = 2.4
Hz, J2,3 = 4.9 Hz, 1H, 2a-H), 4.57–4.64 (m, 3H, 3a-H, OCH2Ph),
4.70, 4.97 (2d, Jgem = 11.8 Hz, 2H, OCH2Ph), 5.00 (d, J1,2 = 3.2 Hz,
1H, 1b-H), 5.53 (d, J1,2 = 5.0 Hz, 1H, 1a-H), 7.24–7.39 (m, 10H, Ph-
H).
13C NMR(125.7 MHz, CDCl3): d = 17.29 (1C, CH3, C-6b), 24.55,
24.97, 26.00, 26.12 (4C, CH3, C(CH3)), 30.50 (1C, CH2, C-2b),
65.28 (1C, CH2, C-6a), 66.70, 66.76 (2C, CH, C-5a, C-5b), 70.35
(2C, 1CH, 1CH2, C-3a, OCH2Ph), 70.61 (1C, CH, C-2a), 71.16 (1C,
CH, C-4a), 74.25 (1C, CH2, OCH2Ph), 75.34 (1C, CH, C-3b), 75.77
(1C, CH, C-4b), 96.31 (1C, CH, C-1a), 97.81 (1C, CH, C-1b),
108.53, 109.22 (2C, Cipso, C(CH3)), 127.33–128.39 (10C, CH, Ph-
CH), 138.70, 138.98 (2C, Cipso).
5j
1); [a]20D = +139.4 (c = 1.8 in CHCl3); [Ref.:
(c = 1.7 in CHCl3)].
[a]23 = –30.5
D
1H NMR (500 MHz, CDCl3): d = 0.67 (s, 3H), 0.83–1.66 (s, 33H),
1.67 (q, J2,1 = J2,3 = J2,2’ = 11.0 Hz, 1H, 2-H), 1.79–1.86 (m, 2H),
1.95–2.02 (m, 3H), 2.22–2.33 (m, 3H, 2’-H), 3.40 (ddd, J5,6’ = 1.8
Hz, J5,6 = 5.2 Hz, J4,5 = 9.7 Hz, 1H, 5-H), 3.48 (t, J3,4 = J4,5 = 9.1 Hz,
1H, 4-H), 3.56–3.62 (m, 1H), 3.64–3.70 (m, 1H, 3-H), 3.68 (dd,
J5,6 = 5.2 Hz, J6’,6 = 10.8 Hz, 1H, 6-H), 3.76 (dd, J5,6’ = 1.7 Hz,
J6’,6 = 10.7 Hz, 1H, 6’-H), 4.54–4.63 (m, 5H, 1-H, 2 x OCH2Ph),
4.68 (d, Jgem = 11.7 Hz, 1H, OCH2Ph), 4.90 (d, Jgem = 10.9 Hz, 1H,
OCH2Ph), 5.34 (d, J = 5.2 Hz, 1H), 7.21–7.35 (m, 15H, Ph-H).
13C NMR(125.7 MHz, CDCl3): d = 11.84, 18.71, 19.35 (3C, CH3),
21.02 (1C, CH2), 22.57, 22.83 (2C, CH3), 23.79, 24.27 (2C, CH2),
28.00 (1C, CH), 28.22, 29.69 (2C, CH2), 31.85 (1C, CH), 31.93 (1C,
CH2), 35.77 (1C, CH), 36.16 (1C, CH2), 36.72 (1C, Cipso), 37.20,
37.29 (2C, CH2, C-2), 38.90, 39.50, 39.75 (3C, CH2), 42.29 (1C,
Characteristic signals for the b-anomer:
1H NMR (500 MHz, CDCl3): d = 1.18 (d, J5,6 = 6.4 Hz, 3H, 6b-
CH3), 1.97–2.12 (m, 1H, 2b-H), 5.49 (d, J1,2 = 5.0 Hz, 1H, 1a-H).
C
ipso), 50.15, 56.10, 56.73 (3C, CH), 69.41 (1C, CH2, C-6), 71.30,
Cholesteryl 3,4-Di-O-benzyl-2-deoxy-a-L-fucopyranoside (20)
This compound was purified by flash chromatography with EtOAc/
hexane (1% Et3N) 1/8→1/4→1/2. White solid; mp 109 °C; Rf:0.66
(EtOAc/hexane 1/2); [a]21D = –72.2 (c = 1.0 in CHCl3).
1H NMR (500 MHz, CDCl3): d = 0.67 (s, 3H), 0.85–1.57 (m, 33H),
1.15 (d, J5,6 = 6.5 Hz, 3H, 6-CH3), 1.76–1.84 (m, 3H), 1.93–2.01 (m,
3H, 2’-H, 2H Chol), 2.17–2.21 (m, 2H, 2-H), 2.32 (dd, J = 3.0 Hz,
J = 13.2 Hz, 1H), 3.41–3.44 (m, 1H), 3.61 (s, 1H, 4-H), 3.87 (q,
73.34, 74.95 (3C, CH2, OCH2Ph), 75.09 (1C, CH, C-5), 78.12,
78.15 (2C, CH, C-4), 79.55 (1C, CH, C-3), 97.91 (1C, CH, C-1),
121.82 (1C, CH), 127.48–128.41 (15C, CH, Ph-CH), 138.33,
138.35, 138.38, 140.65 (4C, Cipso).
Methyl-O-(3,4-di-O-benzyl-2-deoxy-a/b-L-fucopyranosyl)-
(1→6)-2,3,4-tri-O-benzyl-a-D-glucopyranoside (18)
MS (MALDI): m/z = 797 [M++Na].
J
5,6 = 6.6 Hz, 1H, 5-H), 3.94–3.96 (m, 1H, 3-H), 4.59–4.64 (m, 2H,
OCH2Ph), 4.69, 4.96 (2d, Jgem = 11.8 Hz, 2H, OCH2Ph), 5.11 (d,
1,2 = 3.3 Hz, 1H, 1-H), 5.32 (d, J = 4.8 Hz, 1H), 7.24–7.39 (m, 10H,
C48H54O9•H2O calcd C 72.71, H 7.12; found C 72.82, H 6.87.
a-Anomer: colorless oil; Rf:0.46 (EtOAc/hexane 1/2); [a]21
–16.2 (c = 1.2 in CHCl3).
=
D
J
Ph-H).
1H NMR (500 MHz, CDCl3): d = 1.12 (d, J5,6 = 6.5 Hz, 3H, 6b-
CH3), 1.91 (dd, J2’,3 = 4.6 Hz, J2’,2 = 12.5 Hz, 1H, 2’b-H), 2.14 (dt,
J1,2 = 3.6 Hz, J2’,2 = J2,3 = 12.3 Hz, 1H, 2b-H), 3.32 (s, 3H, OCH3),
3.42–3.51 (m, 3H, 2a-H, 4a-H, 6a-H), 3.57 (s, 1H, 4b-H), 3.68–3.71
(m, 1H, 5a-H), 3.77–3.81 (m, 2H, 5b-H, 6a-H), 3.86–3.90 (m, 1H,
3b-H), 3.98 (t, J2,3 = J3,4 = 9.2 Hz, 1H, 3a-H), 4.52–4.58 (m, 4H, 1a-
H, 1.5*OCH2Ph), 4.67 (d, Jgem = 12.1 Hz, 1H, OCH2Ph), 4.68 (d,
13C NMR (125.7 MHz, CDCl3): d = 11.85, 18.72, 19.38 (3C, CH3),
17.34 (1C, CH3, C-6), 21.05 (1C, CH2), 22.57, 22.82 (2C, CH3),
23.82, 24.29 (2C, CH2), 28.01 (1C, CH), 28.23, 29.54 (2C, CH2),
31.20 (1C, CH2, C-2), 31.89 (2C, CH, CH2), 35.78 (1C, Cipso), 36.19
(1C, CH), 36.74, 37.40, 38.70, 39.51, 39.78 (5C, CH2), 42.31 (1C,
Cipso), 50.15, 56.13, 56.73 (3C, CH), 66.61 (1C, CH, C-5), 70.42,
74.29 (2C, CH2, OCH2Ph), 75.64 (1C, CH, C-3), 75.88 (1C, CH, C-
4), 76.09 (1C, CH), 95.91 (1C, CH, C-1), 121.67 (1C, CH), 127.23–
128.36 (10C, CH, Ph-CH), 138.76, 138.97, 140.70 (3C, Cipso).
MS (MALDI): m/z = 721 [M++Na].
Jgem = 11.7 Hz, 1H, OCH2Ph), 4.78–4.89 (m, 4H, 1b-H, 1.5 x
OCH2Ph), 4.95 (d, Jgem = 11.7 Hz, 1H, OCH2Ph), 4.99 (d,
Jgem = 10.8 Hz, 1H, OCH2Ph), 7.23–7.39 (m, 25H, Ph-H).
13C NMR (125.7 MHz, CDCl3): d = 17.24 (1C, CH3, C-6b), 30.61
(1C, CH2, C-2b), 54.96 (1C, CH3, OCH3), 66.02 (1C, CH2, C-6a),
66.65 (1C, CH, C-5b), 70.06 (1C, CH, C-5a), 70.24, 73.31, 74.34
(3C, CH2, OCH2Ph), 74.84 (1C, CH, C-3b), 75.04 (1C, CH2,
OCH2Ph), 75.63 (1C, CH, C-4b), 75.81 (1C, CH2, OCH2Ph), 77.90
(1C, CH, C-4a), 80.01 (1C, CH, C-2a), 82.16 (1C, CH, C-3a), 97.84
(1C, CH, C-1a), 98.09 (1C, CH, C-1b), 127.33–128.45 (25C, CH,
Ph-CH), 2 x 138.16, 138.55, 138.69, 138.88 (5C, Cipso).
C47H68O4 calcd C 80.97, H 9.84; found C 80.46, H 9.53.
Benzyl-O-(3,4-di-O-benzyl-2-deoxy-a-L-fucopyranosyl)-(1→4)-
(2,6-di-O-benzyl-b-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-ben-
zyl-a/b-D-glucopyranoside (21)
The crude product was purified by flash chromatography with
EtOAc/hexane (1% Et3N) 1/10→1/4. Colorless oil; Rf:0.12
(EtOAc/hexane 1/4).
1H NMR (500 MHz, CDCl3): d = 1.17 (d, J5,6 = 6.5 Hz, 3H, 6c-
CH3), 1.93 (dd, J2’,3 = 4.5 Hz, J2,2’ = 12.6 Hz, 1H, 2’c-H), 2.16 (ddd,
J2,1 = 3.7 Hz, J2’,2 = J2,3 = 12.4 Hz, 1H, 2c-H), 3.33 (t, J = 5.9 Hz,
1H), 3.33–3.36 (m, 1H), 3.44–3.62 (m, 6H), 3.63 (bs, 1H, 4c-H),
3.71 (dd, J = 1.4 Hz, J = 10.1 Hz, 1H, 6’-H), 3.80 (dd, J = 4.0 Hz,
Characteristic signals for the b-anomer:
1H NMR (250 MHz, CDCl3): d = 1.17 (d, J5,6 = 6.5 Hz, 3H, 6b-
CH3), 3.36 (s, 3H, OCH3).
Synthesis 1999, No. SI, 1411–1422 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of Deoxy Glycosides Under Neutral Conditions in LiClO4/Solvent Mixtures
1421
J = 10.8 Hz, 1H, 6-H), 3.87 (d, J = 3.2 Hz, 1H), 3.89–3.93 (m, 1H,
3c-H), 3.97 (q, J5,6 = 6.6 Hz, 1H, 5c-H), 4.00 (t, J = 9.3 Hz, 1H),
4.37–4.42 (m, 3H, 1-H, OCH2Ph), 4.48 (d, J1,2 = 7.7 Hz, 1H, 1-H),
4.58–4.75 (m, 10H, OCH2Ph), 4.90 (d, Jgem = 10.8 Hz, 1H,
OCH2Ph), 4.94–4.99 (m, 3H, OCH2Ph), 5.25 (d, J1,2 = 3.5 Hz, 1H,
1c-H), 7.20–7.41 (m, 40H, Ph-H).
13C NMR (125.7 MHz, CDCl3): d = 17.42 (1C, CH3, C-6c), 30.82
(1C, CH2, C-2c), 67.30 (1C, CH), 68.04, 68.62 (2C, CH2, C-6a, C-
6b), 69.25 (1C, CH), 70.43, 70.94 (2C, CH2, OCH2Ph), 72.63 (1C,
CH), 73.21, 73.42, 74.43, 75.00 (4C, CH2, OCH2Ph), 75.10 (2C,
CH), 75.21, 75.36 (2C, CH2, OCH2Ph), 75.52, 76.48, 79.43, 79.49,
81.73, 82.95 (6C, CH), 100.13 (1C, CH, C-1c), 102.52, 102.58 (2C,
CH, C-1a, C-1b), 127.15–128.43 (40C, CH, Ph-CH), 137.54,
138.10, 138.16, 138.41, 138.45, 138.59, 138.74, 139.15 (8C, Cipso).
4.76 (d, Jgem = 12.3 Hz, 1H, OCH2Ph), 4.82 (d, J1,2 = 3.8 Hz, 1H, 1b-
H), 5.51 (d, J1,2 = 5.0 Hz, 1H, 1a-H), 7.26–7.40 (m, 10H, Ph-H).
13C NMR (125.7 MHz, CDCl3): d = 18.10 (1C, CH3, C-6b), 24.42,
24.93, 25.99, 26.17 (4C, CH3, C(CH3)), 31.47 (1C, CH2, C-2b),
65.47 (1C, CH2, C-6a), 65.78 (1C, CH, C-5a), 69.06 (1C, CH, C-
3b), 69.95 (1C, CH2, OCH2Ph), 63.56, 70.45, 70.67, 70.88 (4C, CH,
C-2a, C-3a, C-4a, C-5b), 70.60 (1C, CH2, OCH2Ph), 79.82 (1C, CH,
C-4b), 96.26 (1C, CH, C-1a), 96.56 (1C, CH, C-1b), 108.52, 108.97
(2C, Cipso, C(CH3)), 127.33–128.30 (10C, CH, Ph-CH), 138.21,
138.79 (2C, Cipso).
Characteristic signals of the b-anomer:
1H NMR (500 MHz, CDCl3): d = 3.11 (dd, J4,3 = 2.9 Hz, J4,5 = 9.1
Hz, 1H, 4b-H), 5.56 (d, J1,2 = 5.0 Hz, 1H, 1a-H).
MS (MALDI): m/z = 1217 [M++Na]. C74H80O14.
Cholesteryl 3,4-Di-O-benzyl-2,6-dideoxy-a/b-D-ribohexopyra-
noside (24)
O-(3,4-Di-O-benzyl-2,6-dideoxy-a/b-D-ribohexopyranosyl)-
(1→6)-2,3,4-tri-O-benzyl-a-D-glucopyranoside (22)
The product was purified by flash chromatography with EtOAc/
hexane (1% Et3N) 1/6→1/2.
The product was purified by flash chromatography with EtOAc/
hexane (1% Et3N) 1/10→1/8. White solid; Rf:0.55 (EtOAc/hexane
1/4).
MS (MALDI): m/z = 720 (M++Na).
MS (MALDI): m/z = 797 [M++Na].
MS (FAB): m/z = 696 (M–-2H).
C48H54O9•H2O calcd C 72.71, H 7.12; found C 72.69, H 7.16.
C47H68O4•0.25 H2O calcd C 80.47, H 9.84; found C 80.30, H 9.57.
b-Anomer:
b-Anomer: colorless oil; Rf:0.45 (ethyl acetate/hexane 1/2;
[a]21D = +43.0 (c = 0.8 in CHCl3).
1H NMR (500 MHz, CDCl3): d = 0.67 (d, J = 2.7 Hz, 3H), 0.85–
1.18 (m, 21H), 1.22–1.41 (m, 5H), 1.28 (d, J5,6 = 6.2 Hz, 3H, 6-
CH3), 1.43–1.57 (m, 8H, 2a-H, 7H Chol), 1.59–1.85 (m, 2H), 1.91–
2.01 (m, 3H), 2.12–2.19 (m, 2H, 2’-H, 1H Chol), 2.29–2.32 (m,
1H), 3.12 (dd, J4,3 = 2.8 Hz, J4,5 = 9.3 Hz, 1H, 4-H), 3.53–3.55 (m,
1H), 3.97–4.02 (m, 2H, 3-H, 5-H), 4.41 (d, Jgem = 11.8 Hz, 1H,
OCH2Ph), 4.55 (d, Jgem = 11.8 Hz, 1H, OCH2Ph), 4.67 (bs, 2H,
OCH2Ph), 4.95 (dd, J1,2’ = 1.8 Hz, J1,2 = 9.6 Hz, 1H, 1-H), 5.35–5.37
(m, 1H), 7.25–7.44 (m, 10H, Ph-H).
1H NMR (500 MHz, CDCl3): d = 1.27 (d, J5,6 = 6.3 Hz, 3H, 6b-
CH3), 1.55–1.61 (m, 1H, 2b-H), 2.14 (ddd, J2’,1 = 2.0 Hz, J2’,3 = 3.6
Hz, J2’,2 = 13.6 Hz, 1H, 2’b-H), 3.11 (dd, J4,3 = 2.7 Hz, J4,5 = 9.2 Hz,
1H, 4b-H), 3.34 (s, 3H, OCH3), 3.51–3.55 (m, 2H, 2a-H, 4a-H), 3.63
(dd, J6’,5 = 4.5 Hz, J6,6’ = 10.9 Hz, 1H, 6’a-H), 3.74–3.76 (m, 1H, 5a-
H), 3.96–4.01 (m, 3H, 3a-H, 3b-H, 5b-H), 4.08 (dd, J6,6’ = J6,5 = 10.1
Hz, 1H, 6a-H), 4.40 (d, Jgem = 11.7 Hz, 1H, OCH2Ph), 4.67–4.50 (m,
5H, OCH2Ph), 4.58 (d, J1,2 = 3.5 Hz, 1H, 1a-H), 4.77–4.89 (m, 3H,
OCH2Ph), 4.84 (dd, J1,2’ = 1.8 Hz, J1,2 = 9.9 Hz, 1H, 1b-H), 4.98 (d,
13C NMR (125.7 MHz, CDCl3): d = 11.86 (1C, CH3), 18.45 (1C,
CH3, C-6), 18.72, 19.36 (2C, CH3), 21.04 (1C, CH2), 22.57, 22.83
(2C, CH3), 23.82, 24.29 (2C, CH2), 28.02 (1C, CH), 28.24, 29.67
(2C, CH2), 31.89 (1C, CH), 31.96 (1C, CH2), 35.79 (1C, CH), 35.91
(1C, Cipso), 36.19 (1C, CH2, C-2), 36.75, 37.33, 38.92, 39.52, 39.78
(5C, CH2), 42.32 (1C, Cipso), 50.18, 56.14, 56.77 (3C, CH), 68.92
(1C, CH, C-3), 71.33 (1C, CH, C-5), 71.37, 71.65 (2C, CH2,
OCH2Ph), 77.82 (1C, CH), 80.78 (1C, CH, C-4), 95.86 (1C, CH, C-
1), 121.69 (1C, CH), 127.29–128.38 (10C, CH, Ph-CH), 138.05,
138.15, 138.70 (3C, Cipso).
J
gem = 10.9 Hz, 1H, OCH2Ph), 7.25–7.36 (m, 25H, Ph-H).
13C NMR (125.7 MHz, CDCl3): d = 18.33 (1C, CH3, C-6b), 35.19
(1C, CH2, C-2b), 55.09 (1C, CH3, OCH3), 67.47 (1C, CH2, C-6a),
69.84 (1C, CH2, C-5a), 69.09, 71.09, 82.12 (3C, CH, C-3a, C-3b, C-
5b), 71.37, 71.61, 73.34, 75.10, 75.77 (5C, CH2, OCH2Ph), 77.81,
79.76 (2C, CH, C-2a, C-4a), 80.73 (1C, CH, C-4b), 98.00 (1C, CH,
C-1a), 98.19 (1C, CH, C-1b), 127.58–128.44 (25C, CH, Ph-CH),
138.02, 138.15, 138.27, 138.51, 138.80 (5C, Cipso).
Characteristic signals of the a-anomer:
1H NMR (500 MHz, CDCl3): d = 1.18 (d, J5,6 = 6.2 Hz, 3H, 6b-
CH3), 1.55–1.61 (m, 2H, 2b-H, 2’b-H), 3.36 (s, 3H, OCH3).
13C NMR (125.7 MHz, CDCl3): d = 18.18 (1C, CH3, C-6b), 55.17
(1C, CH3, OCH3), 94.88 (1C, CH, C-1a).
Characteristic signals of the a-anomer:
1H NMR (500 MHz, CDCl3): d = 1.25 (d, J5,6 = 6.4 Hz, 3H, 6-CH3),
3.16 (dd, J3,4 = 3.0 Hz, J4,5 = 9.0 Hz, 1H, 4-H), 4.94 (d, J1,2 = 4.4 Hz,
1H, 1-H).
O-(3,4-Di-O-benzyl-2,6-dideoxy-a/b-D-ribohexopyranosyl)-
(1→6)-1,2:3,4-di-O-isopropylidene-a-D-galactopyranoside (23)
The product was purified by flash chromatography with ethyl ace-
tate/hexane (1% Et3N) 1/6→1/4. Colorless oil; Rf:0.43 (EtOAc/hex-
ane 1/2).
13C NMR (125.7 MHz, CDCl3): d = 94.09 (1C, CH, C-1).
The analytical data recorded for 2-deoxyglucosyl disaccharides
13,5j,8b 146 and 177 are in accordance with reported values.
MS (FAB): m/z = 569 [M+-H]. C32H42O9.
Acknowledgement
a-Anomer:
This research was supported by the Deutsche Forschungsgemein-
schaft and the Fonds der Chemischen Industrie.
1H NMR (500 MHz, CDCl3): d = 1.26 (d, J5,6 = 6.4 Hz, 3H, 6b-
CH3), 1.29, 1.32, 1.44, 1.51 (4s, 12H, C(CH3)), 1.63 (dt,
J
1,2 = J2,3 = 3.8 Hz, J2’,2 = 14.9 Hz, 1H, 2b-H), 2.36 (dd, J2’,3 = 2.6
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Synthesis 1999, No. SI, 1411–1422 ISSN 0039-7881 © Thieme Stuttgart · New York

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Article Identifier:
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