A convenient synthesis of fluoroalkyl and fluoroaryl glycosides using Mitsunobu conditions

Article abstract of DOI:10.1016/S0008-6215(99)00089-0

A new procedure for the synthesis of fluoroalkyl and fluoroaryl glycosides from primary, secondary, and tertiary fluoroalkyl alcohols and pentafluorophenol using Mitsunobu conditions is reported. Copyright (C) 1999 Elsevier Science Ltd.

Full text of DOI:10.1016/S0008-6215(99)00089-0

www.elsevier.nl/locate/carres
Carbohydrate Research 318 (1999) 171–179
Note
A convenient synthesis of fluoroalkyl and fluoroaryl
glycosides using Mitsunobu conditions
David Gueyrard a, Patrick Rollin a,*, Truong Thi Thanh Nga b, Miche`le Oure´vitch b,
Jean-Pierre Be´gue´ b,1, Danie`le Bonnet-Delpon b
a Institut de Chimie Organique et Analytique, Uni6ersite´ d’Orle´ans, BP 6759, F-45067 Orle´ans, France
b BIOCIS, URA CNRS 1843, Faculte´ de Pharmacie, rue J.B. Cle´ment, F-92296 Chaˆtenay-Malabry, France
Received 8 February 1999; accepted 10 April 1999
Abstract
A new procedure for the synthesis of fluoroalkyl and fluoroaryl glycosides from primary, secondary, and tertiary
fluoroalkyl alcohols and pentafluorophenol using Mitsunobu conditions is reported. © 1999 Elsevier Science Ltd. All
rights reserved.
Keywords: Glycosylation; Fluoroalkyl and fluoroaryl glycosides; Mitsunobu reaction
In other respects, such amphiphiles also dis-
To date, fluoroalkyl glycosides have re-
ceived moderate attention in carbohydrate
chemistry. 1,1-Difluoroalkyl glucosides have
been investigated as a new class of irre-
versible inhibitors of yeast a-glucosidase [1];
fluoroalkyl derivatives of N-acetylmuramyl-
play interesting thermotropic liquid-crys-
talline properties [5a,b]. In most cases,
however, the fluorinated segment was sepa-
rated from the sugar moiety by a two- or
three-methylene spacer arm.
In contrast, fluoroalkyl glycosides with
only one carbon between the fluoroalkyl
moiety and O-1 are not common. For in-
stance, trifluoroethyl glycosides have been
isolated in low yields in solvolytic reactions
L
-alanyl- -isoglutamine were reported as im-
D
munogenic agents [2]. Perfluoroalkylated
monosaccharides which contain the strongly
hydrophobic perfluoroalkyl chain and a bio-
compatible polar head group were shown to
be surfactants and emulsifiers for biomedical
applications [3]. The sugar may allow spe-
cific in vivo recognition and hence such sub-
stances may be capable of drug targeting [4].
of
D
-glucopyranosyl derivatives in trifl-
uoroethanol [6]. Some years ago, Vasella and
co-workers described the formation of
fluoroalkyl glucosides through the insertion
of a glycosylidene carbene—generated from
an anomeric diazirine under thermal and/or
photolytic conditions—into fluoroalkyl alco-
hols and pentafluorophenol [7,8]. However,
* Corresponding author. Fax: +33-23-849-4579.
E-mail address: patrick.rollin@univ-orleans.fr (P. Rollin)
1 Also corresponding author.
the synthesis of the per(O-benzylated)-
gluco-diazirine precursor requires five steps
D
-
0008-6215/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(99)00089-0

172
D. Gueyrard et al. / Carbohydrate Research 318 (1999) 171–179
from 2,3,4,6-tetra-O-benzyl-
D
-glucopyranose
investigated the preparation of fluoroalkyl ac-
etals from dihydroartemisinin, a semisynthetic
derivative of the natural diterpenic endoperox-
ide artemisinin [11]. We have thus observed
that the best general method to prepare
fluoroalkyl derivatives of this type of complex
lactol was the Mitsunobu reaction whatever
the class (primary, secondary or tertiary) of
the fluorinated alcohol involved.
The efficiency of the Mitsunobu procedure
in the case of fluoroalkoxylation has been
previously reported by Falck et al. [12] for the
synthesis of non-symmetric polyfluoroethers.
The reaction was effective even with sterically
hindered 1,1,1,3,3,3-hexafluoro-2-phenyliso-
propyl alcohol [13] and perfluoro-tert-butyl
alcohol [14]. The low pKa of fluorinated alco-
and moreover this thermally unstable diazirine
has to be stored at −25°C. This approach is
therefore not really convenient from a syn-
thetic point of view. More recently, the elec-
trochemical condensation of fluorinated
alcohols initiated by anodic oxidation of
triphenylphosphine [9] or the radical addition
of perfluoroalkyl iodides to double bonds us-
ing sodium dithionite as initiator [5b] were
also shown to result in fluoroglycosides. Ex-
pectedly, the standard Koenigs–Knorr gly-
cosidation approach gave poor results, thus
reflecting the low nucleophilicity of highly
fluorinated alcohols [10].
With a view to studying antimalarials with
prolonged plasma half-life, we have recently
Scheme 1.

Table 1
Yields and physicochemical data for fluoralkyl and fluoralkyl glycosides 1–18
Fluorinated
glycosides
Formula
Eluent (petroleum ether–ethyl
acetate)
Isolated yield
(%)
M+H
a:b
[h]D (c 1,
CHCl3) (°)
Mp (°C)
Elemental analyses
Calcd
Found
a
a
1a,b
2a,b
3
C36H37F3O6 9:1
C37H36F6O6 19:1
C43H40F6O6 19:1
C40H35F5O6 19:1
C28H29F3O5 19:1
C29H28F6O5 9:1
C32H27F5O5 19:1
C36H37F3O6 9:1
C37H36F6O6 19:1
C36H37F3O6 9:1
C14H21F3O6 19:1
C15H20F6O6 19:1
C21H24F6O6 9:1
C18H19F5O6 17:3
C16H22F6O6 19:1
C29H36F6O18 3:2
C29H36F6O18 3:2
C20H19F5O10 4:1
91
645 (M+Na) 20:80
691 15:85
789 (M+Na) 100:0 +56
707 65:35
525 (M+Na) 80:20
C, 69.44; H,
5.99
C, 64.34; H,
5.25
C, 67.35; H,
5.26
C, 67.98; H,
4.99
C, 66.92; H,
5.82
C, 61.05; H,
4.95
C, 65.52; H,
4.64
C, 69.44; H,
5.99
C, 64.34; H,
5.25
C, 69.44; H,
5.99
C, 49.12; H,
6.18
C, 43.91; H,
4.91
C, 51.85; H,
4.97
C, 50.71; H,
4.49
C, 45.29; H,
5.23
C, 44.28; H,
4.61
C, 69.15; H,
5.65
C, 64.19; H,
5.18
97
56
136
C, 67.73; H,
5.58
a
4a,b
5a,b
6a,b
7
80 b
73
n.d. c
a
a
a
a
a
a
C, 66.74; H,
5.71
n.d.
79
571
587
623
691
623
15:85
29 d
66
100:0 +69
85:15
C, 65.68; H,
4.78
C, 69.24; H,
5.87
C, 64.62; H,
5.37
C, 69.59; H,
6.14
C, 49.35; H,
6.31
C, 44.07; H,
5.04
C, 51.63; H,
4.79
C, 50.53; H,
4.34
/
8a,b
9
50
0:100 +40
65:35
10a,b
11
67
85
365 (M+Na) 0:100 +47
51
318
a
12
83
411
487
427
425
787
787
515
0:100 +50
0:100 +11
0:100 +10
15:85
(
a
a
a
a
a
13
26
7
14
64
179
15a,b
16a,b
17a,b
18
31
C, 45.56; H,
5.42
n.d.
97 d
57 d
79
25:75
5:95
C, 44.28; H,
4.61
C, 46.70; H,
3.72
n.d.
0:100 −10
145
C, 46.94; H,
3.83
a With the exception of 3, 11 and 18, which spontaneously crystallized, all compounds were obtained as syrups.
1
b Because of persistent C6F5OH contamination, the yield was estimated by H NMR.
c n.d., not determined.
1
d Because of persistent DEADH2 contamination, the yield was estimated by H NMR.

Table 2
1H NMR chemical shifts (l in ppm) and coupling constants (J in Hz) for fluorinated glycosides of benzylated sugars
Fluorinated
glycosides
H-1
H-2
H-3
H-4
H-5
H-6
Rf
1a
1b
4.84, J1,2 3.9
4.53, J1,2 7.8
3.63, J2,3 11.8 4.03, n.d. a
3.72, n.d.
3.75, J4,5 9.4
3.80, n.d.
3.50, J5,6a 2.3
3.72, n.d.
3.70, J5,6b 4.4
3.93, JH,F 8.7
4.01, 4.28, JH,H 12.4, JH,F 8.7,
3.50, J2,3 8.6
3.70
JH,F 8.5
n.d.
n.d.
2a
2b
3
4a
4b
5a
5b
6a
6b
4.99, J1,2 3.8
4.50, J1,2 7.2
5.39, J1,2 3.5
5.55, J1,2 3.4
5.00, J1,2 7.6
4.77, J1,2 3.7
4.49, J1,2 7.4
4.84, J1,2 3.9
4.75, J1,2 6.8
3.50
3.40, J2,3 8.0
3.69, J2,3 10.0 4.27, J3,410.0
3.81, J2,3 10.0 4.22, n.d.
3.80, n.d.
3.57, J2,3 9.6
3.45, J2,3 8.9
3.63, J2,3 11.8 n.d.
3.95
3.50, n.d.
n.d.
3.50, J4,5 9.3
3.92, J4,5 10.0 4.18, J5,6a 2.2
3.82, J4,5 10.0 4.26, J5,6a 2.7
3.80, J4,5 9.2
n.d.
3.30, n.d.
n.d.
3.68, J4,5b 7.8 3.38, 4.01, J4,5a 4.5,
J5a,5b 11.9
n.d.
3.30, J5,6a 2.3
n.d.
3.50, J5,6b 4.5
3.72, 3.94, J6a,6b 10.8
3.67, n.d.
3.67, J5,6b 3.2
n.d.
n.d.
n.d.
/
n.d.
3.80, n.d.
3.9, n.d.
3.65, n.d.
3.46, n.d.
n.d.
3.30, n.d.
n.d.
3.80, n.d.
4.00, 4.02, n.d.
4.58, JH,F 6.0
n.d.
3.53, J2,3 9.0
3.65, J3,4 8.0
n.d.
318
7
5.42, J1,2 3.5
3.64, J2,3 9.8
4.11, J3,4 9.4
3.64, J4,5b 11.1 3.75, 3.95, J4,5a 5.6,
J5a,5b 11.2
n.d.
(
8a
8b
9
4.81, J1,2 2.0
4.19, J1,2 0.0
5.14, J1,2 0.0
3.75, J2,3 3.0
n.d.
3.90, J2,3 3.1
3.85, J3,4 9.3
n.d.
3.91, J3,4 7.0
3.99, J4,5 9.3
n.d.
4.12, J4,5 9.0
3.70, n.d.
n.d.
3.90, J5,6a 1.8
3.60, 3.70, n.d.
3.65, 3.75, n.d.
3.72, 3.83, J5,6b 4.4,
J6a,6b 10.9
3.75, n.d.
3.62, 3.80, n.d.
5.9, n.d.
1
179
10a
10b
4.76, J1,2 3.7
4.3, J1,2 6.7
3.8, n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
3.7, n.d.
3.7, 4.0, n.d.
a n.d., not determined.

Table 3
1H NMR chemical shifts (l in ppm) and coupling constants (J in Hz) for fluorinated glycosides of 2,3:5,6-di-O-isopropylidene-
D
-mannofuranose
Fluorinated
glycosides
H-1
H-2
H-3
H-4
H-5
H-6a
H-6b
Rf
CMe2
11
5.03, J1,2 0.0
4.64, J2,3 5.9
4.77, J3,4 3.6
3.95, J4,57.4
4.37, J5,6a 6.4 3.97, J6a,6b 8.8 4.07, J5,6b 4.5 3.81–3.87, JH,H
1.29, 1.34,
12.2, JH,F 8.6, JH,F 1.40, 1.43
8.5
12
5.20, J1,2 0.0
5.26, J1,2 0.0
5.35, J1,2 3.2
5.42, J1,2 0.0
5.38, J1,2 0.0
4.74, J2,3 5.8
4.89, J2,3 5.8
4.87, n.d.
4.83, J3,4 3.5
4.93, J3,4 3.4
4.87, n.d.
4.02, J4,5 7.6
4.19, J4,5 7.9
3.93, J4,5 8.3
n.d.
4.38, J5,6a 6.4 3.93, J6a,6b 8.7 4.08, J5,6b 4.6 4.40, JH,F 6.0
1.31, 1.35,
1.40, 1.43
1.34, 1.39,
1.39, 1.48
1.36, 1.40,
1.40, 1.59
n.d.
13
4.36, J5,6a 6.3 4.00, J6a,6b 8.8 4.09, J5,6b 4.5 7.5–7.6, n.d. a
4.55, J5,6a 4.3 3.99, J6a,6b 9.0 4.04, J5,6b 4.2
14
/
15a
15b
4.73, J2,3 5.9
4.72, J2,3 5.9
4.90, J3,4 3.6
4.84, J3,4 3.6
n.d.
3.65, J6a,6b
3.82, J5,6b 3.1 2.10, n.d.
11.4, J5,6a 6.0
4.04, J4,5 7.7
4.36, J5,6a 6.5 3.94, J6a,6b 8.7 4.08, J5,6b 4.8 1.70, n.d.
1.32, 1.37,
1.42, 1.46
a n.d., not determined.
318
(
7
Table 4
1H NMR chemical shifts (l in ppm) and coupling constants (J in Hz) for fluorinated glycosides of disaccharides
179
Fluorinated
glycosides
H-1
H-2
H-3
H-4
H-5
H-6a
H-6b
H-1%
H-2%
H-3%
H-4%
H-5%
H-6a%
H-6b%
Rf
16a
16b
5.71, J1,2 5.3 n.d. a
4.80, J1,2 7.6 4.90, J2,3 8.9
n.d.
5.24, J3,4 8.9
n.d.
4.03, J4,5 9.6
n.d.
n.d.
n.d.
4.30, J5,6b
4.3
4.56, J5,6b
3.4
5.46, J1%,2% 4.0 n.d.
5.40, J1%,2% 4.1 4.83, J2%,3%
10.6
n.d.
n.d.
n.d.
n.d.
4.05, J6a%,6b%
12.4
4.03, J6a%,6b%
12.5
n.d.
4.25, J5,6b%
2.4
4.33, J5,6b%
2.4
n.d.
4.47, JH,F 5.9
3.74, J5,6a 3.1 4.54, J6a,6b
5.33, J3%,4% 9.6 5.03, J4%,5% 9.9 3.95, J5%,6a%
12.2
3.65, J5,6a 6.0 4.07, J6a,6b
12.1
6.5
17a
4.74, J1,2 7.6 4.97, J2,3 9.3
5.70, J3,4 9.2
3.82, J4,5 9.8
4.52, J1%,2% 7.9 4.90, J2%,3% 9.4 5.13, J3%,4% 9.4 5.04, J4%,5% 9.5 3.65, J5%,6a%
4.44, JH,F 6.0
4.5
a n.d., not determined.

176
D. Gueyrard et al. / Carbohydrate Research 318 (1999) 171–179
Table 5
13C NMR chemical shifts (l in ppm) and coupling constants (J in Hz) for fluorinated glycosides of benzylated sugars
Fluorinated
glycosides
C-1
C-2 C-3
C-4 C-5
C-6 Rf
2
1
1a
1b
2a
2b
3
4a
4b
5a
5b
6a
6b
7
8a
8b
9
10a
10b
97.9 79.7 81.6
103.7 81.7 84.4
99.5 81.1
103.5 81.3 84.0
95.1 81.5 80.3
101.2 79.3 81.3
105.0 82.0 84.3
97.8 79.4 80.9
104.1 81.3 83.3
77.3 71.0
77.5 75.1
68.2 64.7, 123.8, JC,F 35.0, JC,F 282.0
68.7 66.0, 123.8
n.d. a n.d. n.d.
n.d. n.d.
2
1
1
77.1 75.3
77.5 72.1
74.4 72.5
77.3 75. 6 67.9 n.d.
77.6 60.5
77.6 64
n.d. n.d.
77.6 64.0
77.3 61.9
74.5 73.0
n.d. n.d.
74.2 73.4
n.d. n.d.
n.d. n.d.
68.5 72.3, 120.9, 121.8, JC,F 30.0, JC,F 280.0, JC,F 283.0
67.9 83.0, 122.1, 123.0, JC,F 29.2, JC,F 287.1, JC,F 289.2
2
1
1
68.3 n.d.
2
1
64.5, 123.8, JC,F 34.8, JC,F 279.0
2
65.9, JC,F 34.8
99.3 80.7
n.d.
n.d.
2
1
1
104.0 80.7 82.7
101.0 79.2 80.8
98.6 74.4 79.7
71.1, 120.8, 121.8, JC,F 34.8, JC,F 282.5, JC,F 287.7
n.d.
2
1
69.0 64.1, 123.7, J
34.7, J
278.3
C,F
C,F
1
101.3
n.d. n.d.
n.d. 63.8, n.d.
1
100.6 74.4 79.1
68.8 72.0, 121.0, 122.02JC,F 32.5, JC,F 281.0, JC,F 283.0
2
1
98.2
103.9
n.d. n.d.
n.d. n.d.
n.d. 64.5, 123.9, JC,F 34.6, JC,F 279.9
2
1
n.d. 65.7, 123.8, JC,F 34.6, JC,F 279.4
a n.d., not determined.
lation between the a/b ratios observed and the
structure and pKa of the fluorinated reactants.
hols [15] allowing better deprotonation under
the Mitsunobu reaction conditions, the result-
ing alkoxide would displace the oxyphospho-
nium leaving group under milder conditions
as compared with non-fluorinated alcohols.
Since the pioneering work of Grynkiewicz on
the formation of phenyl glycosides [16], O-gly-
cosylation using a Mitsunobu reaction has
been performed only with phenolic nucle-
ophiles [17].
The synthesis of fluoroalkyl glycosides was
therefore investigated under Mitsunobu condi-
tions with regard to diverse parameters (type
of fluorinated alcohol, sugar series, nature of
the protective group, etc.). The reaction pro-
ceeded under comparatively mild conditions
representing a special variant of the Mit-
sunobu protocol in which the fluoroalcohol,
due to its acidity (pKa 9–12), acts as the
proton donor/nucleophile. The fluoroalkyl
and fluoroaryl glycosides prepared from di-
versely protected mono- and disaccharides are
shown in Scheme 1 and characterized in Table
1.
Experimental
General methods.—Evaporation was con-
ducted in vacuo with a Buchi rotary evapora-
tor. Optical rotations were determined at
20 °C with a Perkin–Elmer model 141 polar-
imeter. Melting points were measured on a
Buchi apparatus and are uncorrected. TLC
was performed on precoated Silica Gel 60F-
254 plates (E. Merck), with detection by UV
light (254 nm) and spraying with a 10% solu-
tion of concd H2SO4 in MeOH followed by
heating. Low-resolution mass spectra (MS)
were measured on a Perkin–Elmer SCIEX
API 300 (ion spray or heated nebulizer). NMR
spectra were performed on a Bruker ARX 400
using two probes: a broad band inverse probe,
equipped with field gradients (1H at 400.13
13
MHz and C at 100.62 MHz) and an inverse
dual 19F/1H probe (19F at 386.6 MHz). All
compounds were dissolved in CDCl3 unless
when dissolution in C6D6 was required for
spectrum interpretation. Total assignment of
the carbon and proton signals was made
The influence of the pKa of the glycosyl
acceptor in Mitsunobu glycosylations has pre-
viously been pointed out [18]: for each sugar
series, we are presently investigating the corre-

Table 6
13C NMR chemical shifts (l in ppm) and coupling constants (J in Hz) for fluorinated glycosides of 2,3:5,6-di-O-isopropylidene-
D
-mannofuranose
CMe2
Fluorinated gly-
cosides
C-1
C-2
C-3
C-4
C-5
C-6
Rf
2
1
11
12
13
14
15a
15b
106.5 84.7 79.2 81.0 72.9 66.6 63.9, 124.0, JC,F 34.9, JC,F 278.1
24.4, 25.1, 25.7, 26.7, 109.2, 112.8
24.3, 25.1, 25.7, 26.6, 109.3, 113.1
24.4, 25.2, 25.7, 26.8, 110.0, 113.0
25.2, 25.2, 25.4, 26.9, 109.5, 115.3
24.3, 24.3, 25.7, 26.7, 109.5, 113.0
24.3, 24.3, 25.7, 26.7, 109.5, 113.0
2
1
1
107.5 84.6 79.2 81.9 72.6 66.6 71.7, 121.0, 121.5, JC,F 33.0, JC,F 285.3, JC,F 286.4
103.9 86.2 79.2 81.6 72.8 66.8 122.7, 123.2, 127.6, 128.5, 128.9, 130.5, JC,F 287.4, JC,F 289.3
1
1
103.5 80.6 78.7 79.4 73.2 66.5 n.d. a
103.0 85.3 79.7 80.0 70.1 64.2 12.1, n.d.
1
103.2 85.5 79.3 81.3 72.7 66.7 12.1, 122.1, JC,F 287.3
a n.d., not determined.
/
Table 7
13C NMR chemical shifts (l in ppm) and coupling constants (J in Hz) for fluorinated glycosides of disaccharides
Fluorinated glycosides
C-1
C-2
C-3
C-4
C-5
C-6
C-1%
C-2%
C-3%
C-4%
C-5%
C-6%
Rf
16a
16b
17a
95.2
100.5
100.7
n.d. a
71.5
71.0
n.d.
74.7
71.9
n.d.
72.3
67.7
n.d.
72.6
73.0
n.d.
62.2
61.1
95.6
95.6
100.8
n.d.
70.0
71.5
n.d.
69.7
72.0
n.d.
68.1
75.9
n.d.
68.6
72.8
n.d.
62.2
61.5
n.d.
73.4, 122.0, n.d.
73.5, 121.0, JC,F 289.0
1
318
)
a n.d., not determined.
1
179
Table 8
19F NMR chemical shifts (l in ppm) and coupling constants (J in Hz) for fluoroalkyl glycosides
Fluo-
1a
1b
2a
2b
3
5a
5b
6b
8a
8b
9
10a
10b
11
12
13
16a
16b
17a
17b
roalkyl
glycosides
CF3
−74.4,
JH,F 8.7
−75.1,
JH,F 8.6
−73.0,
n.d. a
−73.6,
−73.5,
n.d.
−68.1,
JF,F 10.8, JH,F 8.7
−75.1
−73.7,
−74.4,
JH,F 8.6
−73.5,
−75.2,
JH,F 8.6
−75.3,
JH,F 8.6
−73.5,
−73.8,
JF,F 9.0,
JH,F 6.0
−73.7,
JH,F 8.6
−74.2,
JH,F 8.6
-74.5,
JH,F 8.6
—74.1,
n.d.
−69.4,
−73.5,
JF,F 10.6
−73.6,
−73.1,
JF,F 9.5,
JH,F 5.9,
JH,F 6.0
−74.1,
−73.9,
JH,F 7.0
−74.1,
−73.9,
JH,F 6.0
−73.2,
−73.5
JH,F 6.3,
JF,F 8.8,
−73.9,
JF,F 9.2
a n.d., not determined.

178
D. Gueyrard et al. / Carbohydrate Research 318 (1999) 171–179
Table 9
19F NMR chemical shifts (l in ppm) and coupling constants (J in Hz) for fluoroaryl glycosides
Fluoroaryl glycosides
4a
4b
7
14
F ortho
F meta
F para
−155.0, J 19.1
−162.9, J 1.9
−161.3, J 21.8
−154.6, J 19.4
−163.2, J 2.0
−161.2, J 22.0
−154.9, J 20.0
−163.0, n.d. a
−161.5, J 22.0
−156.0, J 18.0
−164.2, J 2.1
−162.9, J 21.9
a n.d., not determined.
After evaporation under reduced pressure, the
residue was chromatographed (see Table 1) on
silica gel.
through COSY, HMQC and HMBC experi-
ments (Tables 2–9). For most compounds, the
determination of the anomeric carbon and
proton chemicals shifts, together with the cou-
pling constant J1,2, allowed the determination
of the a (J1,2 4 Hz) or b (J1,2 7 Hz) structure.
In the case of furanosidic compounds, the J1,2
value was not informative: homonuclear-
NOESY and heteronuclear NOE-difference
experiments allowed the attribution of the b
anomeric configuration to compounds 15b
and 14, respectively. When neither homo- or
hetero-NOE experiments gave structural in-
formation (compounds 11, 12 and 13), only
the comparison of the chemical shift values of
some specific carbons (C-5 and C-6) with
those of unambiguously determined com-
pounds (15b and 14) allowed their anomeric
Pentafluorophenyl 2,3,4,6-tetra-O-acetyl-i-
D
-glucopyranoside (18).—1H NMR (CDCl3):
5.31–5.24 (m, 2H, H-2 and H-3), 5.19 (t, 1H,
J4,3=J4,5 9.1 Hz, H-4), 5.00 (d, 1H, J1,2 7.2
Hz, H-1), 4.26 (dd, 1H, J6a,6b 12.4 Hz, J6a,5 5.0
Hz, H-6a), 4.11 (dd, 1H, J6b,5 2.6 Hz, H-6b),
3.73 (m, 1H, H-5), 2.08, 2.04 and 2.01 (3s,
12H, 4CH3CO); 13C NMR (CDCl3): 170.9–
169.6 (4CO), 144.2–130.8 (CF), 102.7 (C-1),
72.7 (C-5 and C-3), 71.5 (C-2), 68.4 (C-4), 61.8
(C-6), 20.9 (4CH3CO).
Acknowledgements
We thank the MENRT and the CNRS for
financial support. The authors also thank Dr
J. Greiner and Dr H. Driguez for valuable
discussions and Dr B. Perly for NMR
expertise.
configuration to be determined as b(
2,3,4,6 - Tetra - O - benzyl - - glucopyranose
[4132 - 28 - 9] was purchased from Sigma and
2,3:5,6-di-O-isopropylidene-a- -mannofura-
nose [14131-84-1] from Aldrich.
D).
D
D
Non-commercially available benzyl pro-
tected hemiacetalic substrates were prepared
through standard acid-catalysed glycoside hy-
drolysis [19]. Disaccharide precursors to com-
pounds 16 and 17 were obtained from maltose
and cellobiose octaacetates, respectively,
through hydrazine acetate-catalyzed selective
transesterification [20].
General procedure for the synthesis of
fluoroalkyl and fluoroaryl glycosides.—To a
stirred solution of the hemiacetalic sugar (1
mmol) in dry toluene (10 mL) were added
triphenylphosphine (2 equiv), the fluorinated
alcohol (2–8 equiv) and diethyl azodicarboxy-
late (2 equiv). The mixture was stirred under
argon atmosphere at room temperature and
monitored by TLC (reaction time: 1.5–48 h).
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