Organofluorine compounds and fluorinating agents, Part 26: New reversed nucleosides - Perfluoroalkyl substituted 1,2,3-triazoles linked to D-galactose and D-altrose

Article abstract of DOI:10.1016/S0022-1139(00)00212-8

Reversed nucleosides, i.e., fluoroalkyl-substituted 1,2,3-triazoles linked to the C-atom 6 of D-galactose and D-altrose were synthesised by 1,3-dipolar cycloadditions using the monosaccharide azides 8, 11 and the perfluoroalkyl substituted phenyl vinyl sulfones 5-7. The starting material 11, methyl 6-azido-3,4-O-(trichloroethylidene)-2-O-cyclohexylcarbamoyl-6-deoxy-α-D- altropyranoside, was synthesized from methyl 2-O-cyclohexylcarbamoyl-3,4-O-(2,2,2-trichloroethylidene)-α-D- altropyranoside (9), via its 6-iododeoxy derivative 10. The homologous dipolarophiles 5-7, (E)-1-perfluoroalkyl-2-phenylsulfonyl-ethenes with a CF₃ (5), n-C₄F₉ (6), and n-C₆F₁₃ (7) group, respectively, were obtained by Wittig-Horner olefination from phosphonate 4 and the corresponding perfluoroalkanals 1-3. Cycloaddition of 6-azido-6-deoxy-1,2:3,4-di-O-isopropylidene-α-D-galactose (8) with the dipolarophiles 5-7 yielded the reversed nucleosides 12-14; altrose azide 11 gave the reversed nucleosides 15 and 16. The products of cycloaddition were deprotected using usual techniques. Thus, the 1-(6-deoxy-1,2:3,4-di-O-isopropylidene-α-D-galactopyranoso-6-yl)-4- perfluoroalkyl-1,2,3-triazoles 13 and 14 were deacetalated by treatment with aqueous trifluoroacetic acid yielding the corresponding 1-(6-deoxy-α-D-galactopyranoso-6-yl)-4-perfluoroalkyl-1,2,3-triazoles 17 and 18. The deprotection of the 1-[methyl 2-O-cyclohexylcarbamoyl-6-deoxy-3,4-O-(2,2,2-trichloroethylidene)-α-D- altropyranosido-6-yl]-4-perfluoroalkyl-1,2,3-triazoles 15 and 16 was made stepwise (hydrodechlorination→deacetalation→decarbamoylation), i.e., the 1-(methyl 6-deoxy-D-altropyranosido-6-yl)-4-perfluoroalkyl-1,2,3-triazoles 23 and 24 were synthesised via the ethylidene acetals 19, 20 and the 1-(methyl 2-O-cyclohexylcarbamoyl-6-deoxy-α-D-altropyranosido-6-yl)-4- perfluoroalkyl-1,2,3-triazoles 21 and 22. For the methyl 6-azido-2-O-cyclohexylcarbamoyl-6-deoxy-3,4-O-(2,2,2-trichloroethylidene)- α-D-altropyranoside (11) an X-ray structure is given.

Full text of DOI:10.1016/S0022-1139(00)00212-8

Journal of Fluorine Chemistry 104 (2000) 135±142
Organo¯uorine compounds and ¯uorinating agents, Part 26
New reversed nucleosides Ð per¯uoroalkyl substituted
1,2,3-triazoles linked to D-galactose and D-altrose$
Christian Hager, Ralf Miethchen*, Helmut Reinke
È
Universitat Rostock, Fachbereich Chemie, Lehrstuhl Organische Chemie II, Buchbinderstrasse 9,
D-18051 Rostock, Germany
Received 25 October 1999; accepted 23 November 1999
Abstract
Reversed nucleosides, i.e., ¯uoroalkyl-substituted 1,2,3-triazoles linked to the C-atom 6 of D-galactose and D-altrose were synthesised by
1,3-dipolar cycloadditions using the monosaccharide azides 8, 11 and the per¯uoroalkyl substituted phenyl vinyl sulfones 5±7. The starting
material 11, methyl 6-azido-3,4-O-(trichloroethylidene)-2-O-cyclohexylcarbamoyl-6-deoxy-a-D-altropyranoside, was synthesized from
methyl 2-O-cyclohexylcarbamoyl-3,4-O-(2,2,2-trichloroethylidene)-a-D-altropyranoside (9), via its 6-iododeoxy derivative 10. The
homologous dipolarophiles 5±7, (E)-1-per¯uoroalkyl-2-phenylsulfonyl-ethenes with a CF3 (5), n-C4F9 (6), and n-C6F13 (7) group,
respectively, were obtained by Wittig±Horner ole®nation from phosphonate 4 and the corresponding per¯uoroalkanals 1±3. Cycloaddition
of 6-azido-6-deoxy-1,2:3,4-di-O-isopropylidene-a-D-galactose (8) with the dipolarophiles 5±7 yielded the reversed nucleosides 12±14;
altrose azide 11 gave the reversed nucleosides 15 and 16. The products of cycloaddition were deprotected using usual techniques. Thus, the
1-(6-deoxy-1,2:3,4-di-O-isopropylidene-a-D-galactopyranoso-6-yl)-4-per¯uoroalkyl-1,2,3-triazoles 13 and 14 were deacetalated by
treatment with aqueous tri¯uoroacetic acid yielding the corresponding 1-(6-deoxy-a-D-galactopyranoso-6-yl)-4-per¯uoroalkyl-1,2,3-
triazoles 17 and 18. The deprotection of the 1-[methyl 2-O-cyclohexylcarbamoyl-6-deoxy-3,4-O-(2,2,2-trichloroethylidene)-a-D-altro-
pyranosido-6-yl]-4-per¯uoroalkyl-1,2,3-triazoles 15 and 16 was made stepwise (hydrodechlorination!deacetalation!decarbamoylation),
i.e., the 1-(methyl 6-deoxy-D-altropyranosido-6-yl)-4-per¯uoroalkyl-1,2,3-triazoles 23 and 24 were synthesised via the ethylidene acetals
19, 20 and the 1-(methyl 2-O-cyclohexylcarbamoyl-6-deoxy-a-D-altropyranosido-6-yl)-4-per¯uoroalkyl-1,2,3-triazoles 21 and 22. For the
methyl 6-azido-2-O-cyclohexylcarbamoyl-6-deoxy-3,4-O-(2,2,2-trichloroethylidene)-a-D-altropyranoside (11) an X-ray structure is given.
# 2000 Elsevier Science S.A. All rights reserved.
Keywords: Fluorinated compounds; 1,2,3-Triazoles; Reversed nucleosides; Carbohydrates; Galactose; Altrose
1. Introduction
nucleoside-analogous compounds like N-glycosylated 4-
halomethyl 1H- or 2H-1,2,3-triazoles are of interest as
radiomimetic substances [8], bactericides, and viricides,
respectively [9±11]. In this paper, we describe ¯uorinated
1,2,3-triazoles linked to a non-glycosidic position of
monosaccharides. The key step of the synthesis is based
on a 1,3-dipolar cycloaddition.
Various natural antibiotics contain carbohydrate moieties
with amino-deoxy structures, e.g., 2-amino-2-deoxy-D-
gulose was detected in streptothricine [2,3] and 3-amino-
3,6-dideoxy-D-mannose was found in the macrolide-anti-
biotic natamycine (pimaricine) [2,4,5]. Properties of bioac-
tive substances are commonly in¯uenced by mimetic
modi®cations of natural or synthetic reference species.
Especially, heterocycles linked to sugars represent an inter-
esting group of such mimetic products. Various 1,2,3-tria-
zole derivatives are biologically active [6,7], e.g.,
2. Syntheses and discussion
Per¯uoroalkyl substituted vinyl sulfones are very favour-
able `building blocks' for syntheses of ¯uorinated hetero-
aromatics by 1,3-dipolar cycloaddition. Such dipolarophiles
are easily accessible by ultrasound-assisted Wittig±Horner
ole®nation [12,13]. We synthesised the (E)-1-per¯uoro-
$ For Part 25, see [1].
* Corresponding author. Fax: ‡49-381-498-1819.
E-mail address: ralf.miethchen@chemie.uni-rostock.de (R. Miethchen)
0022-1139/00/$ ± see front matter # 2000 Elsevier Science S.A. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ( 0 0 ) 0 0 2 1 2 - 8

136
C. Hager et al. / Journal of Fluorine Chemistry 104 (2000) 135±142
Scheme 1. Synthesis of (E)-1-perfluoroalkyl-2-phenylsulfonyl-ethenes by
Wittig±Horner olefination.
alkyl-2-phenylsulfonyl-ethenes 5±7 by ultrasound-assisted
Wittig±Horner ole®nation from the phosphonate 4 and the
per¯uoroalkanals 1±3, Scheme 1. Because ¯uoral (1) is
gaseous, the procedure for the preparation of 5 was slightly
modi®ed compared to that for 6 and 7. The vinyl sulfones 5±
7 were isolated in yields of 51±58%.
The structures of 5±7 are supported by their NMR
spectra. In ¯uorinated alkenes of the type XCF2±CH=CHR,
the observed couplings 4JH;F are always <1 Hz (0.4±0.9 Hz)
if the a-CF2-group and the corresponding hydrogen are
trans. If they are on the same side (cis), values of
4JH;Fꢀ1.5±2.5 Hz are observed [14]. Accordingly to this
4JH;F couplings of 1.5±1.6 Hz were found for the vinylsul-
fones 5±7 indicating a trans-arrangement of the per¯uor-
oalkyl and the phenylsulfonyl group.
The azides 8 [15] and 11 required as 1,3-dipoles for the
synthesis of the per¯uoroalkyl substituted 1,2,3-triazoles
were prepared by conventional procedures. The synthesis
of the methyl 6-azido-2-O-cyclohexylcarbamoyl-6-deoxy-
3,4-O-(2,2,2-trichloroethylidene)-a-D-altropyranoside (11)
from 9 [16] via 10 is shown in Scheme 2. Its structure is
supported by an X-ray analysis (Fig. 1). The Puckering
Fig. 1. X-ray structure of methyl 6-azido-2-O-cyclohexylcarbamoyl-6-
deoxy-3,4-O-(2,2,2-trichloroethylidene)-a-D-altropyranoside (11); 30%
probability of the terminal ellipsoids. The fragment A, viewed from
another perspective, shows the exact conformation of the pyranose ring.
aromatisation follows spontaneously the cyclisation step
as a result of elimination, because the sulfonyl function
is an excellent leaving group.
We synthesised the 4-per¯uoroalkyl substituted 1,2,3-
triazoles 12±16 by 1,3-dipolar cycloaddition of the azides
8 and 11 with the homologous vinyl sulfones 5±7 in
re¯uxing toluene. It is noteworthy, that only a single regioi-
someric 1,2,3-triazole derivative was formed in each of
these reactions. Thus, the azide 8 yielded exclusively the
4-per¯uoroalkyl-1,2,3-triazole derivatives 12±14 in yields
of 72±75%. The cycloaddition of the azide 11 with the vinyl
sulfones 6 and 7 gave the crystalline 4-per¯uoroalkyl-1,2,3-
triazole derivatives 15 and 16 in 40% yield, Scheme 3.
The structure of the 1,2,3-triazole derivatives 12±16 was
supported by their 1H, 13C, and 19F NMR spectra completed
by a 1H-NOE measurement of compound 13. A signi®cant
Ê
parameters [17,18] of 11 (Qˆ0.504 A, yˆ22.68, jˆ342.58)
indicate that the pyranose ring adopts a conformation which
4
intermediate between an ideal C1 chair (yˆ08), a 8E half
boat (yˆ54.78, jˆ0 or 3608), and a 8H5 half chair con-
formation (yˆ50.88, jˆ330.08). The altrose ring is sepa-
rately depicted in Fig. 1 to show its special conformation.
Numerous studies, including many with azidodeoxy
sugars, have shown that 4-substituted 1,2,3-triazole deriva-
tives may be generated in 1,3-dipolar cycloadditions with
dipolarophiles based on monosubstituted acetylenes [19].
Beck and GuÈnther [20] have shown that 1,2-disubstituted
phenylsulfonyl-ethenes are likewise very favourable
dipolarophiles for 1,2,3-triazole syntheses. In this case,
Scheme 2. Synthesis of methyl 6-azido-2-O-cyclohexylcarbamoyl-6-
deoxy-3,4-O-(2,2,2-trichloroethylidene)-a-D-altropyranoside (11).
Scheme 3. 1,3-dipolar cycloadditions of the azides with vinyl sulfones.

C. Hager et al. / Journal of Fluorine Chemistry 104 (2000) 135±142
137
2-O-cyclohexylcarbamoyl-6-deoxy-a-D-altropyranosido-6-
yl)-4-per¯uoroalkyl-1,2,3-triazoles 21, 22, respectively, in
good yields. Subsequently, the altroses 21 and 22 were
decarbamoylated by re¯uxing in methanolic sodium
methoxide yielding 23 and 24, respectively, Scheme 4.
The microanalyses and NMR spectra of the deprotected
compounds correspond to the structures presented in
Scheme 4.
Fig. 2. 1H-NOE correlation of triazole±H and methylene protons of
compound 13; a weak correlation was also found between the triazole±H
and H-1 of the galactose moiety.
3. Experimental
Sonication: VIBRACELLVCX-400, 20 kHz, 6 or 13 mm
probe, 120 W electrical input; melting points: Leitz Labor-
lux 12 Pol equipped with a hot stage Mettler FP 90; H,
correlation of the triazole±H with the methylene protons
(H-6, H-60) of the sugar moiety indicates that the 4-per-
¯uoroalkyl regioisomer (not the 5-isomer) was formed
(Fig. 2).
1
13CfHg, and 13FfHg NMR spectra: Bruker instruments: AC
250 and ARX 300, internal standard TMS; optical rotation:
Polar LmP (IBZ Mebtechnik); Column chromatography: E.
Merck Silica Gel 60 (63±200 mm); thin layer chromatogra-
phy (TLC): E. Merck Silica Gel 60 F254 foils. Chemicals:
BuLi (Aldrich), AIBN (Fluka), Bu3SnH (Aldrich), 2,2,2-
tri¯uoroethanal methylhemiacetal (HOECHST AG),
Amberlite IR 120 (Fluka).
For the X-ray structure determination a crystal of 11 was
checked by a rotational photograph and a suitable reduced
cell was found by the automatic cell determination routine.
The data collection was performed in routine o-scan, the
structure was solved by direct methods (Siemens
SHELXTL, 1990, Siemens Analytical X-ray Inst.) and
re®ned by the full matrix least-squares method of Siemens
SHELXTL, Vers.5.03. All non-hydrogen atoms were
re®ned anisotropically. The H-atoms were put into theore-
tical positions and re®ned using the riding model.
The sugar moieties of the D-galactose derivatives 13, 14
and the D-altrose derivatives 15, 16 were deprotected
using usual procedures, Scheme 4. Because trichloroethy-
lidene acetal groups are acid-stable, the D-altrose derivatives
15, 16 were ®rst converted into the ethylidene derivatives 19
and 20 by treatment with tributyltin hydride under radical
conditions [21,22]. The stepwise hydrodechlorination of 15
and 16 via the dichloro- and the monochloro derivatives
may be followed by TLC, because the two intermediates
are easily detectable. The isopropylidene acetals in 13, 14
and the ethylidene acetals in 19, 20 were cleaved by
treatment of the compounds with aqueous tri¯uoroacetic
acid (TFA) giving the 1-(6-deoxy-D-galactopyranoso-6-yl)-
4-per¯uoroalkyl-1,2,3-triazoles 17, 18 and the 1-(methyl
Ê
Diffractometer: Siemens P4; Radiation: lˆ0.71073 A
(Mo±Ka) with graphite monochromator; crystal size:
0.50 mmÂ0.45 mmÂ0.22 mm; formula: C16H23Cl3N4O6;
formula weight: 473.73; temperature 293(2) K; crystal sys-
tem: monoclinic; space group: P21; unit cell dimensions:
Ê
Ê
Ê 3
Ê
aˆ6.054(2) A, bˆ13.078(5) A, cˆ13.835(4) A, bˆ
93.09(2)8; volume: 1093.8(6) A ; Zˆ2; density (calcu-
lated): 1.438 Mg/m3; absorption coef®cient: 0.458 mm
;
1
F(0 0 0): 492; Y range for data collection: 2.14±21.988;
index ranges: 6ꢁhꢁ6, 14ꢁkꢁ14, 14ꢁlꢁ14; re¯ec-
tions collected: 3127; independent re¯ections: 2692;
R(int)ˆ0.0339, completeness to Yˆ21.988, 99.9%; data/
restraints/parameters: 2692/1/262; goodness- of- ®t on F2:
1.046; ®nal R indices [I>2s (I)]: R1ˆ0.0434, wR2ˆ0.1131;
R indices (all data): R1ˆ0.0454, wR2ˆ0.1154; largest diff.
Ê 3
peak and hole: 0.167 and 0.195 e/A . Crystallographic
data (excluding structure factors) for the structure of 11 have
been deposited with the Cambridge Crystallographic Data
Centre as supplementary publication no. CCDC-135 212.
Copies of the data can be obtained free of charge on
application to The Director, CCDC, 12 Union Road, Cam-
bridge CB2 1EZ, UK (fax: Int. code ‡(1223) 336±033; e-
mail: deposit@ccdc.cam.ac.uk).
Scheme 4. Deprotection of the carbohydrate moieties.

138
C. Hager et al. / Journal of Fluorine Chemistry 104 (2000) 135±142
3.1. (E)-1-trifluoromethyl-2-phenylsulfonyl-ethene (5)
C14H7F13O2S (486.3) Calc. C 34.58, H 1.45, S 6.59;
Found C 34.42, H 1.48, S 6.79%.
Tri¯uoroethanal (1) was generated from 1,1,1-tri¯uoro-
ethanal methylhemiacetal (12.92 g, 0.1 mol) by dropwise
addition of syrupy phosphoric acid at 1208C with stirring.
The gaseous compound was condensed in a freezing trap at
788C, which already contained the phosphonate 4 (5.33 g,
20 mmol) dissolved in THF (100 ml). Under stirring, butyl
lithium (15.6 ml of a 1.6 M solution in hexane) was drop-
wise added to this mixture by syringe through a septum and
stirring was continued at 788C for 1 h. The mixture was
allowed to warm to r.t. within 2 h and was worked-up as
described for the homologue 6. Yield of 5: 2.41 g (51%);
RFꢀ0.24 (heptane±EtOAc, 20:1, v/v), m.p. 658C (pentane);
[23] 66±66.58C.
3.4. Methyl 2-O-cyclohexylcarbamoyl-6-deoxy-6-iodo-3,4-
O-(2,2,2-trichloroethylidene)-a-D-altropyranoside (10)
To a solution of methyl 2-O-cyclohexylcarbamoyl-3,4-O-
(2,2,2-trichloroethylidene)-a-D-altropyranoside (9) [16]
(2.24 g, 5.0 mmol) and Ph3P (1.97 g, 7.50 mmol) in
15 ml dry toluene imidazole (1.02 g, 15.0 mmol) and iodine
(1.90 g, 7.50 mmol) was added and the mixture was re¯uxed
with vigorous stirring for about 35 min. (TLC control).
After decantation and treatment of the solid with EtOAc
(twice 10 ml), the combined organic phases were subse-
quently washed with 10 ml of 3% aq. Na2S2O4 solution and
water (twice 10 ml), dried (MgSO4) and concentrated under
reduced pressure. The residue was puri®ed by column
3.2. (E)-1-(1,1,2,2,3,3,4,4,4-nonafluorobutyl)-2-
phenylsulfonyl-ethene (6)
chromatography (RFˆ0.42; heptane±EtOAc, 6:1, v/v).
23
Yield: 2.37 g (85%), glass-like solid; ‰aŠ ‡57.88 (CHCl3,
D
Under sonication and argon atmosphere butyl lithium
(0.7 ml, 1.1 mmol of a 1.6 M solution in hexane) was slowly
added to a solution of phosphonate 4 (292 mg, 1.0 mmol) in
THF (25 ml) at r.t. Sonication was continued for 30 min and
then per¯uoropentanal (2) [13] (248 mg, 1.0 mmol) dis-
solved in THF (5 ml) was added using a syringe. After
30 min. saturated NH4Cl solution (25 ml) and diethyl ether
(25 ml) were added to the mixture. The organic phase was
separated and the extraction of 6 was completed with ether
(10 ml). The combined organic phases were washed with
saturated aq. NaHCO3 solution (25 ml) and water (25 ml),
dried (Na2SO4) and concentrated under reduced pressure.
The residue was puri®ed by column chromatography
(RFꢀ0.30, heptane±EtOAc, 20:1, v/v) yielding 0.20 g
(52%) of sulfone 6, m.p. 64±668C (pentane).
cˆ1.15).
1H-NMR (250.1 MHz, CDCl3): dˆ5.47 (s, 1H, acetal±
H), 5.07 (dd, 1H, 3J1=2ꢀ1.7 Hz, 3J2=3ꢀ3.6 Hz, H-2), 4.68 (d,
1H, H-1), 4.62±4.72 (m, 1H, NH), 4.60 (dd, 1H,
3
3J3=4ꢀ5.8 Hz, H-3), 4.33 (dd, J4=5ꢀ8.9 Hz, H-4), 3.70
3
3
(ddd, 1H, J5=6ꢀ2.6 Hz, J5=6'ꢀ8.5 Hz, H-5), 3.60 (dd,
3
1H, J6=6'ꢀ10.9 Hz, H-6), 3.48 (s, 3H, OMe), 3.38±3.47
(m, 1H, cyclohexyl±CH), 3.27 (dd, 1H, H-60), 1.84±2.00 (m,
2H, cyclohexyl±CH2), 1.52±1.77 (m, 3H, cyclohexyl±CH2),
1
1.04±1.44 (m, 5H, cyclohexyl±CH2); 13Cf Hg-NMR
(75.5 MHz, CDCl3): dˆ154.2 (carbamoyl±C=O), 107.0
(acetal±C), 99.3 (C-1), 99.3 (CCl3), 76.7, 76.5, 68.6, 66.8
(C-2,3,4,5), 56.1 (OMe), 50.2 (cyclohexyl±CH), 33.2, 25.4,
24.7 (cyclohexyl±CH2), 5.4 (C-6).
C16H23Cl3INO6 (558.6): Calc. C 34.40, H 4.15, N 2.51;
Found C 34.67, H 4.01, N 2.63%.
1H NMR (300.1 MHz, CDCl3): dˆ7.56±7.95 (m, 5H,
3
4
phenyl±H), 7.06 (dt, 1H, JH-1=H-2ꢀ15.3 Hz, JH-2=a-CF
ꢀ
2
3
1.6 Hz, H-2), 6.88 (dt, 1H, JH-1=a-CF ꢀ11.2 Hz, H-1);
3.5. Methyl 6-azido-2-O-cyclohexylcarbamoyl-6-deoxy-
3,4-O-(2,2,2-trichloroethylidene)-a-D-altropyranoside (11)
2
19Ff Hg NMR (235.4 MHz, CDCl3): dˆ 80.7 (CF3),
1
113.1 (a-CF2), 123.6, 125.4 (b,g-CF2).
C12H7F9O2S (386.2): Calc. C 37.32, H 1.83, S 8.30;
Found C 37.33, H 2.07, S 8.44%.
A solution of 10 (2.79 g, 5.0 mmol) and NaN3 (0.36 g,
5.50 mmol) in dry DMF (10 ml) was stirred for 3 h at
1208C. Subsequently, the mixture was cooled down, poured
on 10 g of ice and extracted with diethyl ether (3Â10 ml).
The combined organic phases were dried (MgSO4), con-
centrated under reduced pressure and the residue was pur-
i®ed by column chromatography (RFˆ0.33; heptane±
3.3. (E)-1-(1,1,2,2,3,3,4,4,5,5,6,6,6-tridecafluorohexyl)-2-
phenylsulfonyl-ethene (7)
Per¯uoroheptanal (3) [13] (348 mg, 1.0 mmol) and phos-
phonate 4 (292 mg, 1.0 mmol) were converted into 7 as
described for the homologue 6. Yield of 7: 0.28 g (58%);
RFꢀ0.26 (heptane±EtOAc, 20:1, v/v), m.p. 798C (pentane).
1H NMR (300.1 MHz, CDCl3): dˆ7.89±7.95 (m, 2H,
phenyl±H), 7.63±7.76 (m, 1H, phenyl±H), 7.57±7.66 (m,
EtOAc, 10:1, v/v). Yield: 2.30 g (97%), m.p. 102±1048C
22
(MeOH); ‰aŠ 51.08 (CHCl3, cˆ1.38).
D
1H-NMR (250.1 MHz, CDCl3): dˆ5.47 (s, 1H, acetal±
H), 5.08 (dd, 1H, 3J1=2ꢀ2.2 Hz, 3J2=3ꢀ3.7 Hz, H-2), 4.68 (d,
1H, H-1), 4.60±4.72 (m, 1H, carbamoyl±NH), 4.62 (dd, 1H,
3
3
3H, phenyl±H), 7.06 (dt, 1H, JH-1=H-2ꢀ15.2 Hz,
3J3=4ꢀ6.3 Hz, H-3), 4.47 (dd, J4=5ꢀ9.7 Hz, H-4), 3.89
3
3
3
4JH-2=a-CF ꢀ1.5 Hz, H-2), 6.89 (dt, 1H, JH-1=a-CF
ꢀ
(ddd, 1H, J5=6ꢀ2.7 Hz, J5=6'ꢀ6.3 Hz, H-5), 3.59 (dd,
2
2
11.3 Hz, H-1); 19Ff Hg NMR (235.4 MHz, CDCl3):
1H, J6=6'ꢀ13.1 Hz, H-6), 3.49 (dd, 1H, H-60), 3.44±3.59
1
2
dˆ 80.5 (CF3),
112.9 (a-CF2),
121.3,
122.7,
(m, 1H, cyclohexyl±CH), 3.43 (s, 3H, OMe), 1.85±2.00 (m,
2H, cyclohexyl±CH2), 1.52±1.78 (m, 3H, cyclohexyl±CH2),
122.7, 125.9 (4 CF2, b,g,d,e-CF2).

C. Hager et al. / Journal of Fluorine Chemistry 104 (2000) 135±142
139
1
1.04±1.45 (m, 5H, cyclohexyl±CH2); 13Cf Hg-NMR
(75.5 MHz, CDCl3): dˆ153.7 (carbamoyl±C=O), 107.1
(acetal±C), 99.2 (CCl3), 99.1 (C-1), 76.5, 73.2, 68.6, 66.7
(C-2, 3, 4, 5), 55.9 (OMe), 52.0 (C-6), 50.3 (cyclohexyl±
CH), 33.2, 25.4, 24.7 (cyclohexyl±CH2).
dˆ 80.8 (CF3), 109.0 (a-CF2), 123.4, 125.3 (b,g-
CF2).
C18H20F9N3O5 (529.4): Calc. C 40.84, H 3.81, N 7.94;
Found C 41.01, H 3.67, N 7.42%.
C16H23Cl3N4O6 (473.7): Calc. C 40.57, H 4.89, N 11.83;
Found C 40.52, H 4.72, N 11.63%.
3.8. 1-(6-Deoxy-1,2:3,4-di-O-isopropylidene-a-D-
galactopyranoso-6-yl)-4-perfluorohexyl-1,2,
3-triazole (14)
3.6. 1-(6-Deoxy-1,2:3,4-di-O-isopropylidene-a-D-
galactopyranoso-6-yl)-4-trifluoromethyl-1,2,
3-triazole (12)
Azide 8 (0.85 g, 3.0 mmol) and vinyl sulfone 7 (1.17 g,
2.40 mmol) dissolved in toluene (15 ml) were re¯uxed for
17 h under argon. The mixture was worked-up as described
for the homologue 12 (RFˆ0.37, toluene±EtOAc, 20:1, v/v).
A solution of 8 (0.85 g, 3.0 mmol) and 5 (0.69 g,
2.40 mmol) in toluene (15 ml) was re¯uxed under argon
atmosphere for 17 h (TLC control). Then the solvent was
evaporated under reduced pressure and the residue was
puri®ed by column chromatography (RFˆ0.29, toluene±
22
D
Yield of 14: 1.12 g (74%), m.p. 145±1468C; ‰aŠ
(CHCl3, cˆ1.05).
34.28
1H NMR (250.1 MHz, CDCl3): dˆ8.09 (s, 1H, triazole±
3
3
H), 5.50 (d, 1H, J1;2ꢀ4.9 Hz, H-1), 4.72 (dd, 1H, J5;6
ꢀ
2
3
3.4 Hz, J6;6 ꢀ14.4 Hz, H-6), 4.65 (dd, 1H, J2;3ꢀ2.6 Hz,
'
EtOAc, 20:1, v/v). Yield of 12: 0.64 g (72%), m.p. 128±
3J3;4ꢀ7.8 Hz, H-3), 4.50 (dd, 1H, 3J5;6'ꢀ8.7 Hz, H-60), 4.33
(dd, 1H, H-2), 4.20 (dd, 1H, H-4), 4.14 (ddd, 1H, H-5), 1.47
(s, 3H, CH3), 1.35 (s, 3H, CH3), 1.33 (s, 3H, CH3), 1.28 (s,
24
D
1308C; ‰aŠ
49.28 (CHCl3, cˆ0.99).
1H NMR (250.1 MHz, CDCl3): dˆ8.04 (q, 1H,
4Jtriazole
ꢀ0.9 Hz, triazole±H), 5.50 (d, 1H, J1;2
ꢀ
3
H=CF3
3H, CH3); 13Cf Hg NMR (75.5 MHz, CDCl3): dˆ125.8
1
3
2
4.7 Hz, H-1), 4.68 (dd, 1H, J5;6ꢀ3.6 Hz, J6;6'ꢀ14.2 Hz,
H-6), 4.64 (dd, 1H, 3J2;3ꢀ2.5 Hz, 3J3;4ꢀ7.6 Hz, H-3), 4.48
(triazole±C), 110.1, 109.2 (2 ketal±C), 96.2 (C-1), 71.2,
70.8, 70.4 (C-2,3,4), 67.1 (C-5), 51.1 (C-6), 25.9, 25.7, 24.8,
(dd, 1H, 3J5;6 ꢀ8.6 Hz, H-60), 4.33 (dd, 1H, H-2), 4.21 (dd,
'
24.3 (4 CH3); 19Ff Hg NMR (235.4 MHz, CDCl3):
1
3
1H, J4;5ꢀ2.0 Hz, H-4), 4.17 (ddd, 1H, H-5), 1.46 (s, 3H,
dˆ 80.5 (CF3),
108.9 (a-CF2)
121.3,
122.6,
CH3), 1.36 (s, 3H, CH3), 1.34 (s, 3H, CH3), 1.28 (s, 3H,
1
122.6, 125.9 (b,g,d,e-CF2).
C20H20F13N3O5 (629.4): Calc. C 38.17, H 3.20, N 6.68;
Found C 38.22, H 3.05, N 6.65%.
CH3); 13Cf Hg NMR (75.5 MHz, CDCl3): dˆ124.4 (q,
3Jtriazole C5=Fꢀ2.9 Hz, triazole±C5), 120.5 (q, JCF =F
ꢀ
1
3
267.8 Hz, CF3), 110.1, 109.2 (2 ketal±C), 96.2 (C-1),
71.1, 70.8, 70.3 (C-2,3,4), 67.0 (C-5), 51.0 (C-6), 25.9,
3.9. 1-[Methyl 2-O-cyclohexylcarbamoyl-6-deoxy-3,4-O-
(2,2,2-trichloroethylidene)-a-D-altropyranosido-6-yl]-4-
perfluorobutyl-1,2,3-triazole (15)
25.8, 24.8, 24.4 (4 CH3); 19Ff Hg NMR (235.4 MHz,
1
CDCl3): dˆ 80.8 (CF3).
C15H20F3N3O5 (379.3): Calc. C 47.50, H 5.31, N 11.08;
Found C 47.45, H 5.26, N 10.96%.
Azide 11 (1.42 g, 3.0 mmol) and vinyl sulfone 6 (0.93 g,
2.40 mmol) dissolved in toluene (15 ml) were re¯uxed for
24 h under argon. The mixture was worked-up as described
3.7. 1-(6-Deoxy-1,2:3,4-di-O-isopropylidene-a-D-
galactopyranoso-6-yl)-4-perfluorobutyl-1,2,
3-triazole (13)
for the compound 12 (RFˆ0.14, heptane±EtOAc, 7:1, v/v).
24
Yield of 15: 0.69 g (40%); m.p. 152±1538C; ‰aŠ ‡38.08
D
(CHCl3, cˆ1.08).
Azide 8 (0.85 g, 3.0 mmol) and vinyl sulfone 6 (0.93 g,
2.40 mmol) dissolved in toluene (15 ml) were re¯uxed for
21 h under argon. The mixture was worked-up as described
1H NMR (250.1 MHz, CDCl3): dˆ8.04 (s, 1H, triazole±
3
H), 5.54 (s, 1H, acetal±H), 5.07 (dd, 1H, J1=2ꢀ2.2 Hz,
3
2
3J2=3ꢀ3.6 Hz, H-2), 4.98 (dd, 1H, J5=6ꢀ2.8 Hz, J6=6'ꢀ
3
for the homologue 12 (RFˆ0.39, toluene±EtOAc, 20:1, v/v).
14.3 Hz, H-6), 4.65 (dd, 1H, J3=4ꢀ5.8 Hz, H-3), 4.64 (d,
22
D
3
Yield of 13: 0.95 g (75%), m.p. 143±1468C; ‰aŠ
(CHCl3, cˆ1.01).
38.08
1H, H-1), 4.59 (d, 1H, JNH=CHꢀ8.5 Hz, carbamoyl±NH),
4.56 (dd, 1H, J5=6'ꢀ8.5 Hz, H-60), 4.37 (dd, 1H,
3
1H NMR (250.1 MHz, CDCl3): dˆ8.09 (s, 1H, triazole±
3J4=5ꢀ9.4 Hz, H-4), 4.08 (ddd, 1H, H-5), 3.32±3.58 (m,
1H, cyclohexyl±CH), 3.07 (s, 3H, OMe), 1.84±2.02 (m, 2H,
cyclohexyl±CH2), 1.50±1.80 (m, 3H, cyclohexyl±CH2),
3
3
H), 5.51 (d, 1H, J1;2ꢀ4.9 Hz, H-1), 4.72 (dd, 1H, J5;6
ꢀ
2
3
3.4 Hz, J6;6 ꢀ14.5 Hz, H-6), 4.65 (dd, 1H, J2;3ꢀ2.6 Hz,
'
3J3;4ꢀ7.7 Hz, H-3), 4.51 (dd, 1H, 3J5;6 ꢀ8.6 Hz, H-60), 4.33
1.02±1.45 (m, 5H, cyclohexyl±CH2); 13Cf Hg NMR
1
'
(dd, 1H, H-2), 4.20 (dd, 1H, H-4), 4.14 (ddd, 1H, H-5), 1.48
(s, 3H, CH3), 1.35 (s, 3H, CH3), 1.34 (s, 3H, CH3), 1.28 (s,
(62.0 MHz, CDCl3): dˆ153.5 (carbamoyl±CO), 126.2 (tria-
zole±C-5), 107.2 (acetal±C), 99.1 (C-1), 99.0 (CCl3), 76.1,
72.9, 68.1, 65.6 (C-2,3,4,5), 55.7 (OMe), 52.0 (C-6), 50.3
(cyclohexyl±CH), 33.2, 25.4, 24.7 (cyclohexyl±CH2);
3H, CH3); 13Cf Hg NMR (75.5 MHz, CDCl3): dˆ125.8
1
(triazole±C), 110.1, 109.2 (2 ketal±C), 96.2 (C-1), 71.2,
70.8, 70.3 (C-2,3,4), 67.1 (C-5), 51.1 (C-6), 25.9, 25.7, 24.8,
19Ff Hg NMR (235.4 MHz, CDCl3): dˆ 80.8 (CF3),
1
24.3 (4 CH3); 19Ff Hg NMR (235.4 MHz, CDCl3):
109.8 (a-CF2), 123.1, 125.3 (b,g-CF2).
1

140
C. Hager et al. / Journal of Fluorine Chemistry 104 (2000) 135±142
C22H24Cl3F9N4O6 (717.8): Calc. C 36.81, H 3.37, N 7.81;
Found C 36.94, H 3.30, N 7.58%.
3.12. 1-(6-Deoxy-D-galactopyranoso-6-yl)-4-
perfluorohexyl-1,2,3-triazole (18)
The galactose derivative 14 (0.63 g, 1.0 mmol) was trea-
ted with 60% aq. TFA (10 ml) as described for the homo-
logue 17. After 2.5 h reaction time 0.55 g (100%) of the
crystalline compound 18 was isolated; on heating decom-
position above 1758C.
3.10. 1-[Methyl 2-O-cyclohexylcarbamoyl-6-deoxy-3,4-O-
(2,2,2-trichloroethylidene)-a-D-altropyranosido-6-yl]-4-
perfluorohexyl-1,2,3-triazole (16)
Azide 11 (1.42 g, 3.0 mmol) and vinyl sulfone 7 (1.17 g,
2.40 mmol) dissolved in toluene (15 ml) were re¯uxed for
32 h under argon. The mixture was worked-up as described
1H NMR (250.1 MHz, DMSO-D6): dˆ8.84 (s, 1H, tria-
1
zole±H); 13Cf Hg NMR (62.9 MHz, DMSO-D6): dˆ127.8
(triazole±C-5), 102.0, 92.8 (C-1), 82.7, 82.1, 76.1, 69.6,
69.0, 68.9, 68.8, 68.5 (C-2, 3, 4, 5), 53.9, 51.9 (C-6);
for the compound 12 (RFˆ0.16, heptane±EtOAc, 7:1, v/v).
23
Yield of 16: 0.79 g (40%); m.p. 150±1518C; ‰aŠ ‡34.18
1
19Ff Hg NMR (235.4 MHz, DMSO-D6): dˆ 80.4 (CF3),
D
(CHCl3, cˆ0.98).
107.6 (a-CF2) 121.5, 122.2, 122.7, 125.9 (b,g,d,e-
CF2).
1H NMR (250.1 MHz, CDCl3): dˆ8.04 (s, 1H, triazole±
3
H), 5.54 (s, 1H, acetal±H), 5.07 (dd, 1H, J1=2ꢀ2.2 Hz,
C14H12F13N3O5 (549.2): Calc. C 30.62, H 2.20, N 7.65;
Found C 30.83, H 2.04, N 7.53%.
3
2
3J2=3ꢀ3.4 Hz, H-2), 4.99 (dd, 1H, J5=6ꢀ2.8 Hz, J6=6'ꢀ
3
14.3 Hz, H-6), 4.65 (dd, 1H, J3=4ꢀ5.8 Hz, H-3), 4.64 (d,
3
1H, H-1), 4.59 (d, 1H, JNH=CHꢀ8.3 Hz, carbamoyl±NH),
4.56 (dd, 1H, J5=6'ꢀ8.6 Hz, H-60), 4.37 (dd, 1H, J4=5
ꢀ
3
3
3.13. 1-(Methyl 2-O-cyclohexylcarbamoyl-6-deoxy-3,4-O-
ethylidene-a-D-altropyranosido-6-yl)-4-perfluorobutyl-
1,2,3-triazole (19)
9.4 Hz, H-4), 4.08 (ddd, 1H, H-5), 3.35±3.56 (m, 1H,
cyclohexyl±CH), 3.06 (s, 3H, OMe), 1.83±2.02 (m, 2H,
cyclohexyl±CH2), 1.48±1.78 (m, 3H, cyclohexyl±CH2),
1.01±1.44 (m, 5H, cyclohexyl±CH2); 13Cf Hg NMR
1
A solution of 15 (1.08 g, 1.50 mmol), Bu3SnH (1.40 ml,
5.25 mmol) and AIBN (15 mg, 0.10 mmol) in dry toluene
(10 ml) was heated at 758C under stirring (Ar atmosphere).
When the reaction was ®nished (10 h, TLC control) the
solution was cooled down and was shaken with 30% aq. KF
(5 ml) for 45 min. Bu3SnF precipitated and was removed by
®ltration. Subsequently, the organic phase was separated,
washed with 3% aq. NaHSO4 and twice with water (15 ml),
dried (MgSO4), and concentrated under reduced pressure.
The residue was puri®ed by column chromatography
(62.0 MHz, CDCl3): dˆ153.4 (carbamoyl±CO), 126.2 (tria-
zole±C-5), 107.1 (acetal±C), 99.1 (C-1), 98.9 (CCl3), 76.1,
72.9, 68.1, 65.7 (C-2,3,4,5), 55.6 (OMe), 52.0 (C-6), 50.3
(cyclohexyl±CH), 33.2, 25.4, 24.7 (cyclohexyl±CH2);
19Ff Hg NMR (235.4 MHz, CDCl3): dˆ 80.5 (CF3),
1
108.6 (a±CF2),
(b,g,d,e-CF2).
C24H24Cl3F13N4O6 (817.8): Calc. C 35.25, H 2.96, N
121.2,
122.2,
122.5,
125.8
6.85; Found C 35.62, H 2.94, N 6.80%.
(RFˆ0.19, toluene±EtOAc, 9:1, v/v) giving 0.65 g (70%)
23
colourless crystals of 19, m.p. 133±1348C; ‰aŠ ‡41.78
3.11. 1-(6-Deoxy-D-galactopyranoso-6-yl)-4-
perfluorobutyl-1,2,3-triazole (17)
D
(CHCl3, cˆ1.01).
1H NMR (250.1 MHz, CDCl3): dˆ8.02 (s, 1H, triazole±
3
A solution of the galactose derivative 13 (0.53 g,
1.0 mmol) in 60% aq. TFA (10 ml) was stirred at r.t..
The deacetalation reaction was complete after about 2.5 h
(TLC control: toluene±EtOAc, 5:1, v/v; RF (13)ˆ0.63).
Water (10 ml) was added and the mixture was concentrated
under reduced pressure. To remove remainders of TFA and
H2O, the residue was dissolved in toluene (5 ml) and the
solution was concentrated under reduced pressure. After
repetition of this procedure the residue was crystallised from
acetone. Yield of 17: 0.45 g (100%) of crystalline product,
on heating decomposition above 1758C.
H), 5.45 (q, 1H, Jacetal
H=ethylidene CH3
5.05 (dd, 1H, 3J1=2ꢀ2.4 Hz, 3J2=3ꢀ4.1, H-2), 4.89 (dd, 1H,
ꢀ4.9 Hz, acetal±H),
3J5=6ꢀ2.3 Hz, JH6=6 ꢀ14.2 Hz, H-6), 4.60 (d, 1H, H-1),
2
4.58 (d, 1H, JNH=CH'ꢀ7.9 Hz, carbamoyl±NH), 4.50 (dd,
3
1H, J5=6'ꢀ8.0 Hz, H-60), 4.18 (dd, 1H, J3=4ꢀ5.4 Hz,
3
3
3
H-3), 4.05 (ddd, 1H, J4=5ꢀ9.5 Hz, H-5), 3.99 (dd, 1H,
H-4), 3.31±3.59 (m, 1H, cyclohexyl±CH), 3.08 (s, 3H,
OMe), 1.83±2.01 (m, 2H, cyclohexyl±CH2), 1.50±1.78
(m, 3H, cyclohexyl±CH2), 1.33 (d, 3H, ethylidene±CH3),
1.01±1.45 (m, 5H, cyclohexyl±CH2); 13Cf Hg NMR
1
(62.0 MHz, CDCl3): dˆ153.7 (carbamoyl±CO), 126.1
(triazole±C-5), 102.2 (acetal±C), 99.3 (C-1), 73.7, 71.4,
68.5, 65.7 (C-2,3,4,5), 55.6 (OMe), 52.0 (C-6), 50.3 (cyclo-
hexyl±CH), 33.2, 25.4, 24.7 (cyclohexyl±CH2), 20.7 (ethy-
1H NMR (250.1 MHz, DMSO-D6): dˆ8.86 (s, 1H, tria-
1
zole±H); 13Cf Hg NMR (75.5 MHz, DMSO-D6): dˆ127.9
(triazole±C-5), 102.3, 93.1 (C-1), 82.9, 82.3, 76.4, 69.8,
1
69.2, 69.1, 69.0, 68.7 (C-2,3,4,5), 54.1, 52.1 (C-6); 19Ff Hg
lidene±CH3); 19Ff Hg NMR (235.4 MHz, CDCl3):
1
NMR (235.4 MHz, DMSO-D6): dˆ 80.7 (CF3), 107.9
(a-CF2), 123.2, 125.5 (b,g-CF2).
C12H12F9N3O5 (449.2): Calc. C 32.08, H 2.69, N 9.35;
dˆ 80.7 (CF3), 108.8 (a-CF2), 123.1, 125.3 (b,g-
CF2).
C22H27F9N4O6 (614.5): Calc. C 43.00, H 4.43, N 9.12;
Found C 43.13, H 4.45, N 8.98%.
Found C 31.68, H 2.88, N 8.91%.

C. Hager et al. / Journal of Fluorine Chemistry 104 (2000) 135±142
141
3.14. 1-(Methyl 2-O-cyclohexylcarbamoyl-6-deoxy-3,4-O-
ethylidene-a-D-altropyranosido-6-yl)-4-perfluorohexyl-
1,2,3-triazole (20)
moyl±CO), 126.3 (triazole±C-5), 99.0 (C-1), 69.4, 68.3,
67.3, 65.3 (C-2,3,4,5), 55.7 (OMe), 51.9 (C-6), 50.3 (cyclo-
1
hexyl±CH), 33.2, 25.4, 24.7 (cyclohexyl±CH2); 19Ff Hg
NMR (235.4 MHz, CDCl3): dˆ 80.7 (CF3), 108.8 (a-
CF2), 123.1, 125.3 (b,g-CF2).
C20H25F9N4O6 (588.4): Calc. C 40.82, H 4.28, N 9.52;
Compound 16 (1.31 g, 1.50 mmol), was reduced to 20 by
treatment for 6 h with Bu3SnH (1.40 ml, 5.25 mmol) and
AIBN (15 mg, 0.10 mmol) in toluene (10 ml) as described
Found C 40.81, H 4.21, N 9.24%.
for the homologue 19 (RFˆ0.19, toluene±EtOAc, 9:1, v/v).
23
Yield: 0.74 g (69%), m.p. 142±1438C; ‰aŠ ‡33.48 (CHCl3,
D
3.16. 1-(Methyl 2-O-cyclohexylcarbamoyl-6-deoxy-a-D-
altropyranosido-6-yl)-4-perfluorohexyl-1,2,
3-triazole (22)
cˆ1.00).
1H NMR (250.1 MHz, CDCl3): dˆ8.03 (s, 1H, triazole±
3
H), 5.43 (q, 1H, Jacetal
3
ꢀ4.9 Hz, acetal±H),
H=ethylidene CH3
3
5.03 (dd, 1H, J1=2ꢀ2.4 Hz, J2=3ꢀ4.1 Hz, H-2), 4.88 (dd,
A solution of the ethylidene acetal 20 (0.71 g, 1.0 mmol)
in 10 ml of 60% aq. TFA was heated and worked-up as
3
2
1H, J5=6ꢀ2.3 Hz, J6=6'ꢀ14.2 Hz, H-6), 4.65 (d, 1H,
3JNH=CHꢀ8.0 Hz, carbamoyl±NH), 4.58 (d, 1H, H-1),
described for the homologue 21 (RFˆ0.31, toluene±EtOAc,
3
4.48 (dd, 1H, J5=6ꢀ 7.5 Hz, H-60), 4.17 (dd, 1H,
23
D
1:1, v/v). Yield of 22: 0.49 g (71%), m.p. 78±808C; ‰aŠ
3J3=4ꢀ5.4 Hz, H-3), 4.04 (ddd, 1H, J4=5ꢀ9.6 Hz, H-5),
3
‡32.38 (CHCl3, cˆ1.02).
3.98 (dd, 1H, H-4), 3.24±3.62 (m, 1H, cyclohexyl±CH),
3.04 (s, 3H, OMe), 1.81±1.99 (m, 2H, cyclohexyl±CH2),
1.49±1.78 (m, 3H, cyclohexyl±CH2), 1.30 (d, 3H, ethyli-
1H NMR (250.1 MHz, CDCl3): dˆ8.04 (s, 1H, triazole±
H), 5.02 (dd, 1H, 3J5=6ꢀ2.4 Hz, 2J6=6'ꢀ14.3 Hz, H-6), 4.90
(dd, 1H, 3J1=2ꢀ1.3 Hz, 3J2=3ꢀ3.4 Hz, H-2), 4.72 (d, 1H, H-
dene±CH3), 0.99±1.42 (m, 5H, cyclohexyl±CH2); 13Cf Hg
1
3
1), 4.59 (dd, 1H, J5=6'ꢀ7.9 Hz, H-60), 4.57 (d, 1H,
NMR (62.0 MHz, CDCl3): dˆ153.8 (carbamoyl±CO),
126.1 (triazole±C-5), 102.1 (acetal±C), 99.4 (C-1), 73.8,
71.5, 68.6, 65.8 (C-2,3,4,5), 55.5 (OMe), 52.3 (C-6), 50.3
(cyclohexyl±CH), 33.2, 25.3, 24.7 (cyclohexyl±CH2), 20.6
3
3JNH=CHꢀ8.3 Hz, carbamoyl±NH), 4.01 (ddd, 1H, J4=5
ꢀ
10.3 Hz, H-5), 3.92±4.00 (m, 1H, H-3), 3.35±3.53 (m, 2H,
H-4, cyclohexyl±CH), 3.15 (s, 3H, OMe), 3.05±3.29 (m, 1H,
3-OH), 2.56±2.80 (m, 1H, 4-OH), 1.82±1.98 (m, 2H, cyclo-
hexyl±CH2), 1.46±1.77 (m, 3H, cyclohexyl±CH2), 1.01±
(ethylidene±CH3); 19Ff Hg NMR (235.4 MHz, CDCl3):
1
dˆ 80.6 (CF3),
108.7 (a-CF2),
121.3,
122.3,
1
1.42 (m, 5H, cyclohexyl±CH2); 13Cf Hg NMR
122.6, 125.9 (b,g,d,e-CF2).
C24H27F13N4O6 (714.5): Calc. C 40.35, H 3.81, N 7.84;
Found C 40.42, H 3.82, N 7.74%.
(75.5 MHz, CDCl3): dˆ153.3 (carbamoyl±CO), 137.3 (tria-
zole±C-4) 126.1 (triazole±C-5), 98.8 (C-1), 69.2, 68.1, 67.2,
65.2 (C-2,3,4,5), 55.4 (OMe), 51.7 (C-6), 50.1 (cyclohexyl±
1
CH), 33.0, 25.1, 24.5 (cyclohexyl±CH2); 19Ff Hg NMR
3.15. 1-(Methyl 2-O-cyclohexylcarbamoyl-6-deoxy-a-D-
altropyranosido-6-yl)-4-perfluorobutyl-1,2,3-triazole (21)
(235.4 MHz, CDCl3): dˆ 80.5 (CF3), 108.6 (a-CF2),
121.3, 122.3, 122.6, 125.9 (b,g,d,e-CF2).
C22H25F13N4O6 (688.4): Calc. C 38.38, H 3.66, N 8.14;
Found C 38.36, H 3.71, N 8.05%.
A solution of 19 (0.61 g, 1.0 mmol) in 60% aq. TFA
(10 ml) was stirred at 508C. The deacetalation reaction was
complete after about 7 h (TLC control). Water (10 ml) was
added and the mixture was concentrated under reduced
pressure. To remove remainders of TFA and H2O, the
residue was dissolved in toluene (5 ml) and the solution
was concentrated under reduced pressure. After repetition of
this procedure, the residue was puri®ed by column chro-
3.17. 1-(Methyl 6-deoxy-a-D-altropyranosido-6-yl)-4-
perfluorobutyl-1,2,3-triazole (23)
A solution of compound 21 (0.59 g, 1.0 mmol) in 1%
methanolic sodium methoxide (10 ml) was heated for 4 h
under re¯ux. The mixture was cooled down, neutralised
with an acidic ion exchanger (Amberlite IR 120), ®ltered,
and the ®ltration residue was washed twice with methanol
(10 ml). The combined methanolic solutions were concen-
trated under reduced pressure and the crude product 23
matography (RFˆ0.31, toluene±EtOAc, 1:1, v/v). Yield of
23
21: 0.40 g (68%), m.p. 78±808C; ‰aŠ ‡40.28 (CHCl3,
D
cˆ0.99).
1H NMR (250.1 MHz, CDCl3): dˆ8.05 (s, 1H, triazole±
H), 5.01 (dd, 1H, 3J5=6ꢀ2.3 Hz, 2J6=6'ꢀ14.3 Hz, H-6), 4.89
(dd, 1H, 3J1=2ꢀ1.3 Hz, 3J2=3ꢀ3.4 Hz, H-2), 4.72 (d, 1H, H-
obtained was crystallised from CHCl3±MeOH (10:1, v/v).
24
3
1), 4.60 (dd, 1H, J5=6'ꢀ7.9 Hz, H-60), 4.59 (d, 1H,
Yield: 0.29 g (62%), m.p. 158±1598C; ‰aŠ ‡51.78 (MeOH,
D
3
3JNH=CHꢀ8.2 Hz, carbamoyl±NH), 4.02 (ddd, 1H, J4=5
ꢀ
cˆ1.03).
10.3 Hz, H-5), 3.89±4.00 (m, 1H, H-3), 3.35±3.53 (m, 2H,
3
1H NMR (300.1 MHz, CD3OD): dˆ8.58 (s, 1H, triazole±
H), 4.98 (dd, 1H, 3J5=6ꢀ2.5 Hz, 2J6=6'ꢀ14.2 Hz, H-6), 4.60
(dd, 1H, 3J5=6'ꢀ9.2 Hz, H-60), 4.51 (d, 1H, 3J1=2ꢀ1.4 Hz, H-
H-4, cyclohexyl±CH), 3.22, (d, 1H, J3=3-OHꢀ9.7 Hz, 3-
OH), 3.02 (s, 3H, OMe), 2.76 (d, 1H, 3J4=4-OHꢀ10.4, 4-OH),
1.81±2.00 (m, 2H, cyclohexyl±CH2), 1.53±1.78 (m, 3H,
cyclohexyl±CH2), 1.01±1.44 (m, 5H, cyclohexyl±CH2);
3
1), 4.16 (ddd, 1H, J4=5ꢀ10.1 Hz, H-5), 3.85 (dd, 1H,
3
3J2=3ꢀ3.5 Hz, J3=4ꢀ3.4 Hz, H-3), 3.78 (dd, 1H, H-2),
1
1
13Cf Hg NMR (62.0 MHz, CDCl3): dˆ153.5 (carba-
3.67 (dd, 1H, H-4), 3.00 (s, 3H, OMe); 13Cf Hg NMR

142
C. Hager et al. / Journal of Fluorine Chemistry 104 (2000) 135±142
2
(75.5 MHz, CD3OD): dˆ137.8 (t, Jtriazole
ꢀ
the NMR spectra, the `Fonds der Chemischen Industrie' for
financial support and the HOECHST AG for the gift of 1-
iodo-perfluoroalkanes.
C-4=a-CF2
2
29.1 Hz, triazole±C-4), 128.9 (t, Jtriazole
triazole±C-5), 102.9 (C-1), 72.2, 71.4, 68.4, 67.1 (C-
ꢀ3.9 Hz,
C-5=a-CF2
2,3,4,5), 55.3 (OMe), 53.5 (C-6); 19Ff Hg NMR
1
(235.4 MHz, CD3OD): dˆ 78.4 (CF3), 105.9 (a-CF2),
120.4, 122.6, (b,g-CF2).
References
C13H14F9N3O5 (463.3): Calc. C 33.71, H 3.05, N 9.07;
Found C 33.45, H 2.84, N 8.99%.
È
[1] M. Hein, R. Miethchen, D. Schwabisch, J. Fluor. Chem. 98 (25)
(1999) 55.
[2] S. Hanessian, T.H. Haskell, The Carbohydrates, Chem. and
Biochem., Vol. IIA, Academic Press, New York, London, 1970,
pp. 139±211.
3.18. 1-(Methyl 6-deoxy-a-D-altropyranosido-6-yl)-4-
perfluorohexyl-1,2,3-triazole (24)
[3] J.S. Brimacombe, Angew. Chem. 83 (1971) 261.
È
[4] Rompp Lexikon Chemie Ð Band 4, Georg Thieme Verlag, Stuttgart,
A solution of compound 22 (0.69 g, 1.0 mmol) in 10 ml
of 60% aq. TFAwas re¯uxed for 7 h (TLC control: RFˆ0.60,
CHCl3±MeOH, 5:1, v/v) and worked-up as described for the
New York, 1998, p. 2817.
[5] O. Ceder, B. Hansson, U. Rapp, Tetrahedron 33 (1977) 2703.
[6] R. BoÈhm, C. Karow, Pharmazie 36 (1981) 243.
[7] H. Dehne, 1,2,3-Triazoles, in Houben-Weyl, Vol. E 8d, Thieme-
Verlag, Stuttgart, 1994, 308 and papers cited therein.
homologue 23. Isolated yield: 0.38 g (68%), m.p. 159±
24
1608C (CHCl3±MeOH); ‰aŠ ‡41.58 (MeOH, cˆ1.02).
D
1H NMR (300.1 MHz, CD3OD): dˆ8.58 (s, 1H, triazole±
H), 4.98 (dd, 1H, 3J5=6ꢀ2.5 Hz, 2J6=6'ꢀ14.2 Hz, H-6), 4.60
(dd, 1H, 3J5=6'ꢀ9.2 Hz, H-60), 4.51 (d, 1H, 3J1=2ꢀ1.4 Hz, H-
[8] A. Contreras, R.M. Sanchez-Perez, G. Alonso, Cancer Chemother.
Pharmacol. 1 (1978) 243.
Â
Â
[9] G.R. Revankar, V.C. Solan, R.K. Robins, Nucl. Acid Res. Ð
Symp. Ser. 9 (1981) 65.
3
1), 4.17 (ddd, 1H, J4=5ꢀ10.1 Hz, H-5), 3.85 (dd, 1H,
[10] O. Makabe, H. Suzuki, S. Umezawa, Bull. Chem. Soc. Jpn. 50
(1977) 2689.
3
3J2=3ꢀ3.5 Hz, J3=4ꢀ3.4 Hz, H-3), 3.78 (dd, 1H, H-2),
1
3.68 (dd, 1H, H-4), 3.00 (s, 3H, OMe); 13Cf Hg NMR
[11] P. Wigerinck, A.v. Aerschot, P. Claes, J. Balzarini, E. De Clercq, P.
Herdewijn, J. Heterocycl. Chem. 26 (1989) 1635.
[12] D. Peters, F. Pautet, H. ElFakih, H. Fillion, J.-L. Luche, J. Prakt.
Chem. 337 (1995) 363.
2
(75.5 MHz, CD3OD): dˆ137.9 (t, Jtriazole
ꢀ
C-4=a-CF2
2
29.0 Hz, triazole±C-4), 128.8 (t, Jtriazole
triazole±C-5), 103.0 (C-1), 72.2, 71.4, 68.5, 67.1 (C-
ꢀ3.7 Hz,
C-5=a-CF2
[13] A.O. Miller, D. Peters, C. Zur, M. Frank, R. Miethchen, J. Fluor.
Chem. 82 (1997) 33.
2,3,4,5), 55.3 (OMe), 53.5 (C-6); 19Ff Hg NMR
1
(235.4 MHz, CD3OD): dˆ 79.8 (CF3), 107.4 (a-CF2),
119.9, 121.2, 121.2, 124.7 (b,g,d,e-CF2).
C15H14F13N3O5 (563.3): Calc. C 31.99, H 2.51, N 7.46;
Found C 31.90, H 2.53, N 7.54%.
[14] W.S. Wadsworth, Org. React. 25 (1977) 73.
[15] A.B. Reitz, R.W. Tuman, C.S. Marchione, A.D. Jordan, C.R.
Bowden, B.E. Maryanoff, J. Med. Chem. 32 (1989) 2110.
[16] R. Miethchen, D. Rentsch, Synthesis (1994) 827.
[17] D. Cremer, J.A. Pople, J. Am. Chem. Soc. 97 (1975) 1354.
[18] G.A. Jeffrey, J.H. Yates, Carbohydr. Res. 74 (1979) 319.
[19] P. Norris, D. Horton, B.R. Levine, Heterocycles 43 (1996) 2643 and
papers cited therein.
Acknowledgements
[20] G. Beck, D. GuÈnther, Chem. Ber. 106 (1973) 2758.
[21] S. Jacobsen, F. Slùk, Acta Chem. Scand. 47 (1993) 1012.
[22] D. Rentsch, R. Miethchen, Carbohydr. Res. 293 (1996) 139.
[23] T. Taguchi, G. Tomizawa, A. Kawara, M. Nakajima, Y. Kobayashi, J.
Fluor. Chem. 40 (1988) 171.
The authors are grateful to Angela Niemann and
Claudia Vinke for technical assistance. Moreover, we thank
Prof. Dr. Manfred Michalik (IfOK Rostock) for recording