Synthesis of homochiral 2-C-perfluoroalkyl substituted D- and L-riboses

Article abstract of DOI:10.1016/S0022-1139(02)00042-8

Homochiral 2-C-perfluoroalkyl substituted D- and L-riboses were synthesized via Barbier, Grignard and Ruppert type reactions. The influence of the size of the perfluoroalkyl groups, attached to C-2, on the furanose/pyranose as well as on the α-furanose/β-

Full text of DOI:10.1016/S0022-1139(02)00042-8

Journal of Fluorine Chemistry 115 (2002) 149±154
Synthesis of homochiral 2-C-per¯uoroalkyl substituted D- and L-riboses
a
Uwe Eilitz , Christoph Bottcher , Lothar Hennig , Alois Haas ,
a
a
b
È
Cecile Boyerb, Klaus Burgera,*
È È
Institut fur Organische Chemie, Universitat Leipzig, Johannisallee 29, D-04103 Leipzig, Germany
a
b
È
Ruhr-Universitat, Bochum FNO 034, D-44780 Bochum, Germany
Received 26 November 2001; received in revised form 29 January 2002; accepted 6 February 2002
Dedicated to Professor H. BuÈrger on the occasion of his 65th birthday.
Abstract
Homochiral 2-C-per¯uoroalkyl substituted D- and L-riboses were synthesized via Barbier, Grignard and Ruppert type reactions. The
in¯uence of the size of the per¯uoroalkyl groups, attached to C-2, on the furanose/pyranose as well as on the a-furanose/b-furanose and
a-pyranose/b-pyranose ratio in solution was studied. # 2002 Elsevier Science B.V. All rights reserved.
Keywords: Stereoselective ¯uoroalkylation reactions; 2-C-hepta¯uoropropyl D-ribose; 2-C-nona¯uorobutyl L-ribose
1. Introduction
dif®cult to achieve when a tri¯uoromethyl group is attached
to C-2 [12]. Consequently, glycosides derived from thus
modi®ed carbohydrates should exhibit improved chemical
and enzymatic stability. A review on ¯uoro sugars [13]
prompts us to disclose a preparatively simple access to
homochiral D- and L-ribose derivatives bearing per¯uor-
oalkyl substituents of different chain length (C3F7 and
C4F9) at C-2 [14]. Incorporation of long per¯uoroalkyl
chains into carbohydrates provides access to compounds
with mesogenic and tenside properties. Surface active com-
pounds of this type are of interest to pharmacy and bio-
chemistry [15,16].
Modi®cation of bioactive compounds by introduction of
¯uorine and ¯uoroalkyl groups is an area of current interest
[1±3]. Fluorine and/or ¯uoroalkyl groups placed in strategic
positions of a molecule may profoundly modify chemical
properties, biological activity and selectivity [4±6]. Further-
more, ¯uorine as well as di¯uoromethyl and tri¯uoromethyl
groups are suitable NMR probes for monitoring transport
and metabolism of drugs by 19F NMR spectroscopy in vitro
and in vivo [7]. The usefulness of 18F-labelled carbohydrates,
especially 2-deoxy-2-[18F]¯uoro-D-glucose to study patho-
physiological processes in man non-invasively using posi-
tron-emission-tomography (PET), led to a widespread
investigation of differently 18F-labelled sugar derivatives [8].
Chemically modi®ed carbohydrates are substructures of
nucleosides exhibiting anti-viral, anti-cancer and anti-HIV
activity [9]. Among the possible modi®cations of the car-
bohydrate ring, the C-2 position is of special interest, since it
has been shown that a methyl group placed at C-2 of a sugar
moiety induces severe conformational changes. The rotation
about the N-glycosidic bond becomes restricted, resulting in
an increased nuclease resistance and consequently in an
enhanced biological activity [10,11]. Reactions at C-1 of
carbohydrates via cationic intermediates are much more
2. Results and discussion
Recently we reported on the synthesis of 2-C-tri¯uoro-
methyl D-L-ribose and D-L-arabinose [17] and of 2-C-tri-
¯uoromethyl D-ribose [18] starting from the readily
available tri¯uoromethyl containing building block methyl
tri¯uoropyruvate. We now describe methodology for stereo-
selective introduction of per¯uoroalkyl groups in a late step
of the synthetic sequence. We tested three methods for
introduction of per¯uoroalkyl groups into D- and L-ribose,
namely the Barbier, the Grignard and the Ruppert reaction.
As substrate we applied benzyl D-3,4-O-isopropylidene-
b-erythro-pentopyranosid-2-ulose and benzyl L-3,4-O-iso-
propylidene-b-erythro-pentopyranosid-2-ulose (1 and 2),
respectively [19] (Scheme 1).
* Corresponding author. Tel.: ‡49-341-9736529;
fax: ‡49-341-9736599.
E-mail address: burger@organik.chemie.uni-leipzig.de (K. Burger).
0022-1139/02/$ ± see front matter # 2002 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ( 0 2 ) 0 0 0 4 2 - 8

150
U. Eilitz et al. / Journal of Fluorine Chemistry 115 (2002) 149±154
Scheme 1.
Scheme 3.
First, we reacted 1 with per¯uorobutyl iodide and Zn in
DMF with soni®cation according to the standard protocol
[20] and under modi®ed conditions without success. This
was not unexpected, since only aldehydes are reported to
give good yields in Barbier type reactions [21], while in the
case of ketones the yields are notoriously low, due mainly to
steric reasons [20,22] (Scheme 2).
this compound the structure of an a-furanose. After a few
days a stable equilibrium mixture consisting of a-furanose
(69%), b-furanose (17%), a-pyranose (<1%) and b-pyranose
(14%) was formed (Scheme 2).
In water solution mutarotation can be observed. For a
freshly prepared solution of 7 in water (c ˆ 1) an optical
rotation was measured ‰aŠ ˆ ‡16:7 which changed during
D
When in a Ruppert type reaction, 1 was treated with
hepta¯uoropropyl trimethylsilane [23] in the presence of
tetrabutylammonium ¯uoride (TBAF) as a catalyst, an oil
was obtained after column chromatography in low yield
(9%). A slight improvement of the yield (25%) was accom-
plished when TBAF was substituted by tetrabutylammo-
nium di¯uorophenylstannate as a catalyst. 19F NMR
spectroscopy of the crude product revealed that only one
diastereomer was formed. Because of the concave geometry
of 1 the carbonyl group should be attacked preferentially
from the Si-site to give the benzyl 2-C-hepta¯uoropropyl-
3,4-O-isopropylidene-b-D-erythro-ribopyranoside (4).
Deblocking of the acetonide protecting group can be
achieved on treatment with diluted acetic acid (60%). Com-
parison of the 13C NMR spectra of benzyl 2-C-hepta¯uor-
opropyl-b-D-ribopyranoside (5) formed in 83% yield with its
2-C-tri¯uoromethyl analogue [13] reveals that the size of the
¯uoroalkyl side chain does not affect conformational equi-
libria profoundly as long as the anomeric OH-function
remains protected (Scheme 3).
one day to ‰aŠ ˆ À13:3.
D
To introduce the per¯uorobutyl group into benzyl-3,4-O-
isopropylidene-b-L-erythro-pento-pyranosid-2-ulose (2) we
choose per¯uorobutyl magnesium bromide, readily prepared
from per¯uorobutyl iodide and ethyl magnesium bromide
[24,25]. Because of the concave shape of the acetone
protected sugar moiety, nucleophilic attack from the Si-site
is unfavorable and CC-bond formation occurs exclusively
from the Re-site to give the C-2 per¯uoroalkyl-substituted L-
ribose derivative 8. Again the yield is low (20%) (Scheme 4).
The acetonide was cleaved on treatment with diluted
acetic acid (60%) to give the corresponding benzyl 2-C-
per¯uoroalkyl-b-L-ribopyranoside 9. The unprotected 2-C-
per¯uorobutyl L-ribose was obtained on hydrogenolysis
(9 ! 10 ! 11) as an oil of only poor water solubility.
Therefore, mutarotation could not be recorded and the
optical rotation was measured in methanol.
The relative amounts of tautomeric forms for 2-C-nona-
¯uorobutyl-L-ribose at equilibrium in D6-acetone at room
temperature are: 80% a-furanose, 11% b-furanose, <1% a-
pyranose and 9% b-pyranose. With increasing size of the
substituents at C-2 the ratio of furanose increases, while the
ratio of pyranose decreases (see Table 1). In the furanose
series a-furanose dominates, where the anomeric OH group
is placed trans in respect to the bulky per¯uoroalkyl group,
while in the pyranose series b-pyranose dominates, where
the anomeric OH function is cis positioned with respect to
Deblocking of the benzyl group by catalytic hydrogena-
tion at room temperature is a surprisingly slow process (4
weeks) and affords the unprotected 2-C-hepta¯uoropropyl
D-ribose 7 in 73% yield as a colorless compound, readily
recrystallized from water. NMR spectra of a freshly prepared
solution in D6-acetone reveals that only a single compound
1
is present. Based on the H and 13C NMR data we ascribe
Scheme 2.

U. Eilitz et al. / Journal of Fluorine Chemistry 115 (2002) 149±154
151
Scheme 4.
Table 1
Relative amounts of tautomeric forms of differently substituted riboses at equilibrium in D6-acetone and D2O
Ribose
a-Furanose
b-Furanose
a-Pyranose
b-Pyranose
References
Ribose*
7
14
21
58
[26]
[27]
[14]
[28]
[18]
2-Desoxy-2-C-fluor-
2
11
21
66
2-C-CH3
2-C-CH2OH*
2-C-CF3
35
42
65, 74*
22
29
21, 18*
28
15
16
12, 7*
13
2, 1*
<1
<1
2-C-C3F7
69
17
14
a
2-C-C4F9
80
11
9
a
L-Configured.
* Data recorded in D2O.
the bulky, equatorially placed per¯uoroalkyl group occupy-
ing the favorable axial position (anomeric effect).
Then a 1 M TBAF solution (0.5 ml) in THF was added
dropwise. After 1 h at 0 8C, the reaction mixture was
warmed up to room temperature. The progress of the reac-
tion was monitored by TLC. When the starting material was
consumed (ca. 4 h), THF was evaporated and the remaining
residue extracted with CH2Cl2. The organic phase was
stirred with water (20 ml). The CH2Cl2 phase was separated
and the water phase extracted with CH2Cl2 (3Â). The
organic phase was dried with MgSO4 and evaporated to
dryness. The remaining oil was puri®ed by column chro-
matography (eluent: EtOAc, RF ˆ 0:87) to give 0.1 g (9%)
of 4 as a colorless oil.
Method B: The reaction was performed in CH2Cl2, tetra-
n-butylammonium di¯uoro-phenylstannate instead of TBAF
was applied as a catalyst. After the reaction was complete
the solvent was evaporated and the residue extracted with
MeOH and treated with TBAF (2.5 mmol). After stirring the
mixture for 12 h, MeOH was distilled off and the residue was
puri®ed by chromatography (see earlier paragraph) to give
0.28 g (25%) of 4.
3. Experimental
3.1. General
Microanalyses were carried out with a Heraeus CNH-O
Rapid apparatus. Melting points were determined on a
Boetius apparatus and are corrected. Mass spectra were
obtained with a MASSLABVG 12-250 instrument (EI,
70 eV). IR spectra were measured with a Genesis Series
FTIR ATI Mattson spectrometer. NMR spectra were
recorded on Varian Gemini 200 (1H 199.96; 13C
50.29 MHz), Gemini 2000 (1H 200.04; 13C 50.31 MHz)
and Gemini 300 (1H 300.8; 13C 75.46 MHz) instruments.
Chemical shifts are reported in parts per million relative to
tetramethylsilane. For 19F NMR spectra, external tri¯uor-
oacetic acid was used as reference. Optical rotations were
measured with a Schmidt and Haensch Polartronic polari-
meter. All solvents were dried by standard methods. Reac-
tions were carried out under dry argon.
‰aŠ ˆ À69:7 (c ˆ 1:4, CHCl ); IR (Nujol) n 1778, 1734,
D
3
1457,1381,1190,1160 cmÀ1;1HNMR(CDCl3):d1.40[s,3H,
C(CH3)2], 1.61 [s, 3H, CH(CH3)2], 3.51 (s, 1H, OH-2), 4.01 (d
2
2
br., 1H, J5a=5b ˆ 12:8 Hz, H-5a), 4.10 (d br, 1H, J5a=5b
ˆ
12:8 Hz, H-5b), 4.33 (dd, 1H, 3J4=3 ˆ 6:8 Hz, 3J4=5 ˆ 2 Hz,
H-4), 4.52 (d, 1H, 2J ˆ 11:8 Hz, CH2a), 4.64 (d, 1H,
3J4=3 ˆ 6:8 Hz, H-3), 4.73 (d, 1H, 2J ˆ 11:8 Hz, CH2b),
5.19 (s, 1H, H-1), 7.26±7.38 (m, 5H, Ph); 13C NMR (CDCl3):
d 25.1 (CH3), 26.4 (CH3), 58.4 (C-5), 68.8 (d, 3JCF ˆ 1:2 Hz,
3.1.1. (À) Benzyl-2-C-heptafluoropropyl-3,4-O-
isopropylidene-b-D-ribopyranoside (4)
Method A: Hepta¯uoropropyl trimethylsilane (0.67 g,
2.75 mmol) was added via syringe to a solution of ben-
zyl-3,4-O-isopropylidene-b-D-pentopyranosid-2-ulose (1)
[28] (0.69 g, 2.5 mmol) in THF at 0 8C under inert gas.
3
C-3), 70.0 (d, JCF ˆ 1:5 Hz, C-3), 70.9 (CH2), 71.2 (C-4),

152
U. Eilitz et al. / Journal of Fluorine Chemistry 115 (2002) 149±154
2
3
‡
‡
‡
72.3 (t, JCF ˆ 26:4 Hz, C-2), 97.4 (t, JCF ˆ 1:9 Hz, C-1),
109.8 [C(CH3)2], 110.0 (tq, 1JCF ˆ 270:0 Hz, 2JCF ˆ 33 Hz,
CF2), 118.6 (qt, 1JCF ˆ 261 Hz, 2JCF ˆ 31:6 Hz, CF3), 121.2
301 (M À OH), 282 (M À 2H2O), 254 (M À OHÀ
‡
‡
CH2OH), 241 (M À HCOOH À CH2OH), 169 (C3F7) ,
‡
‡
‡
97 (C5H7O2) , 55 (C3H3O) , 41 (C2HO) .
1
2
(tt, JCF ˆ 278:9, JCF ˆ 33:9 Hz, CF2), 128.3 (C-4, Ph),
128.6 (C-2, 6, Ph), 128.9 (C-3, 5, Ph), 136.7 (C-1, Ph); 19F
NMR(CDCl3):dÀ47.57(dd,1F,2J ˆ 289:1 Hz,J ˆ 6:1 Hz,
CF2), À45.85 (dd, 1F, 2J ˆ 288:4 Hz, J ˆ 6:1 Hz, CF2),
À40.63 (ddq, 2J ˆ 291:5 Hz, J ˆ 18:4 Hz, J ˆ 10:7 Hz,
CF2), À37.79 (ddq, 1F, 2J ˆ 293 Hz, J ˆ 15:2 Hz, J ˆ
3.2. Relative amounts of tautomeric forms at equilibrium
in D6-acetone
3.2.1. a-Furanose (69%)
1H NMR: d 3.59 (dd, 1H, J5a=5b ˆ 12:6 Hz, J5a=4
ˆ
ˆ
2
3
‡
‡
2
10:7 Hz, CF2), À2.85 (m, CF3); MS, EI (m/z): 433 (M À
4:5 Hz, H-5a), 3.70 (m, 1H, H-4), 3.78 (d, 1H, J5a=5b
‡
‡
3
CH3), 390 (M À acetone), 357 (M À Bn), 299 (M À
12:6 Hz, H-5b), 4.25 (d, 1H, J4=3 ˆ 8:1 Hz, H-3), 5.43 (s,
1H, H-1); 13C NMR: d 60.6 (C-5), 69.8 (C-3), 81.0 (C-4), 95.4
(C-1), signal of C-2 could not be extracted because of
low intensity; 19F NMR: d À47.63 (dd, 1F, 2J ˆ 291:3,
J ˆ 4:7 Hz, CF2), À45.10 (dd, 1F, 2J ˆ 292:9 Hz,
J ˆ 6:2 Hz, CF2), À43.80 (m, 2F, CF2), À3.0 (m, 3F, CF3).
‡
‡
‡
acetone À Bn), 253 (C7H4F7O2) , 169 (C3F7) , 91 (C7H7) ,
‡
‡
59 (C3H7O) , 43 (C2H3O) . Anal. Found: C, 48.11; H
4.20%. Calcd. for C18H19F7O5 (448.35): C, 48.22; H, 4.27%.
3.1.2. (À) Benzyl-2-C-heptafluoropropyl-b-D-
ribopyranoside (5)
A solution of benzyl-2-C-hepta¯uoropropyl-3,4-O-iso-
propylidene-b-D-ribopyranoside (4) (0.054 g, 0.12 mmol)
in 60% AcOH (5 ml) was stirred at 40±50 8C for 24 h.
The crude product obtained after evaporation to dryness
was recrystallized from THF/hexanes to give 5 as colorless
crystals 0.041 g (83%), mp: 165±166 8C.
3.2.2. b-Furanose (17%)
1H NMR:
d
3.66 (dd, 1H, 2J5a=5b ˆ 12:5 Hz,
3J4=5 ˆ4:2 Hz, H-5a), 3.89 (d, 1H, 2J5a=5b ˆ12:5 Hz, H-5b),
3.95 (m, 1H, H-4), 4.01 s, 1H, H-3), 4.78 (s, 1H, H-1);
13C NMR: d 63.2 (C-5), 71.3 (C-3), 83.9 (C-4), 100.9 (C-1),
signal of C2 could not be extracted because of low intensity;
19
2
‰aŠ ˆ À87:5 (c ˆ 0:48, acetone); IR (KBr): n 1474,
F NMR: d À47.00 (dd, 1F, J ˆ 286:3 Hz, J ˆ 10:7 Hz,
D
1458, 1384, 1310, 1267, 1206, 1185, 1141 cmÀ1
;
1H
CF2), À44.20 (ddd, 1F, 2J ˆ 286:8 Hz, J ˆ 10:7 Hz,
J ˆ 6 Hz, CF2), À38.50 (dm, 1F, 2J ˆ 293:0 Hz, CF2),
2
NMR (CDCl3):
3J5a=4 ˆ 1:8 Hz, H-5a), 4.06 (dd, 1H, J5a=5b ˆ 12:6 Hz,
d
3.84 (dd, 1H, J5a=5b ˆ 12:6 Hz,
À36.30
(ddt,
1F,
2J ˆ 288:3 Hz,
J ˆ 21:3 Hz,
2
3J5b=4 ˆ 1:3 Hz, H-5b), 4.14 (m, 1H, H-4), 4.22±4.24 (m,
J ˆ 10:7 Hz, CF2), À2.55 (m, 3F, CF3).
2
2H, H-3, OH-3), 4.58 (d, 1H, J ˆ 11:7 Hz, CH2), 4.77 (d,
2
3.2.3. a-Pyranose (<1%), b-Pyranose (14%)
1H, J ˆ 11:7 Hz, CH2), 5.11 (s, 1H, H-1), 5.25 (d, 1H,
1H NMR: d 3.13 (dd, 1H, 2J5a=5b ˆ 8:9 Hz, J5a=4 ˆ 6:2 Hz,
3JHÀ4=OHÀ4 ˆ 4:5 Hz, OH-4), 5.54 (s, 1H, OH-2), 7.36±7.42
(m, 5H, Ph); 13C NMR (CDCl3): d 63.5 (C-5), 64.7 (t,
3JCF ˆ 1:9 Hz, C-3), 70.0 (CH2), 71.3 (C-4), 78.9 (t,
2JCF ˆ 22:1 Hz, C-2), 99.9 (C-1), 110±122 (m,
CF2CF2CF3), 128.1 (C-4, Ph), 128.2 (C-2, 6, Ph), 128.8
(C-3, 5, Ph), 137.8 (C-1, Ph); 19F NMR (CDCl3): d À46.72
H-5a),3.48(dd,1H,2J ˆ 8:9 Hz,3J5b=4 ˆ 6:1 Hz,H-5b),4.10
(s, 1H, H-3), 5.22 (s, 1H, H-1), H-4 could not be extracted; 13
C
NMR: d 73.6 (C-5), 64.8 (C-3), 99.9 (C-1), C-2 and C-4 could
not be extracted because of low intensity; 19F NMR: d À46.34
(dd, 1F, 2J ˆ 289:8 Hz, J ˆ 10:7 Hz, CF2), À42.98 (dd, 1F,
2J ˆ 289 Hz, J ˆ 9:2 Hz, CF2), À39.05 (ddq, 1F, 2J ˆ
288:5 Hz, J ˆ 10:7 Hz, CF2), À35.03 (ddq, 1F, 2J ˆ
293.0 Hz,J ˆ25:8 Hz,J ˆ 13:5 Hz,CF2),À3.20(m,3F,CF3).
2
(dd, 1F, J ˆ 286:1 Hz, J ˆ 12:5 Hz, CF2), À44.20 (ddd,
2
1F, J ˆ 286:3 Hz, J ˆ 11:8 Hz, J ˆ 7 Hz, CF2), À38.27
2
(ddq, 1F, J ˆ 293:8 Hz, J ˆ 29:3 Hz, J ˆ 10:0 Hz, CF2),
2
À35.03 (ddq, 1F, J ˆ 293 Hz, J ˆ 25:5 Hz, J ˆ 12:8 Hz,
‡
3.2.4. (‡) Benzyl-3,4-O-isopropylidene-2-C-
CF2), À2.55 (m, CF3); MS, EI (m/z): 317 (M À Bn), 299
‡
‡
‡
perfluorobutyl-b-L-ribopyranoside (8)
(M À Bn À H2O),
283
(M À OBn À H2O),
271
‡
‡
A solution of per¯uorobutyl iodide (1.02 g, 2.95 mmol) in
dry ether (10 ml), under inert gas and exclusion of light, was
cooled to À45 8C and treated with ethylmagnesium bromide
(2.97 ml, 1 M in THF). After stirring the reaction mixture at
À45 8C for 0.5 h benzyl-3,4-O-isopropylidene-erythro-L-
pentopyranosid-2-ulose (2) [29] (0.68 g, 0.15 mmol) in ether
(5 ml) was added. The reaction mixture was warmed up to
room temperature within 3 h and afterwards treated with a
saturated solution of NH4Cl. Then the mixture was extracted
with ether, the organic phase was dried with MgSO4 and
evaporated to dryness. The crude reaction product was
puri®ed by column chromatography (eluent: CH2Cl2,
RF ˆ 0:53) to give 0.25 g (20%) 8 as colorless crystals,
mp: 68±70 8C.
(M À BnO À CH2O), 241 (C6H4F7O2) , 169 (C3F7) ,
‡
‡
91 (C7H7) , 43 (C2H3O) . Anal. Found: C, 44.13; H
3.68%. Calcd. for C15H15F7O5 (408.29): C, 44.54; H, 3.75%.
3.1.3. (À) 2-C-Heptafluoropropyl-D-ribose (7)
A mixture of benzyl-2-C-hepta¯uoropropyl ribopyrano-
side (5) (0.012 g, 0.03 mmol) and a catalyst (10% Pd/C) in
dry MeOH was stirred in an atmosphere of hydrogen until
the starting material was completely consumed (ca. 4 weeks,
19F NMR analysis). After ®ltration, the organic phase was
evaporated to give an oil, which crystallized slowly. Crystal-
lization from H2O gave 7, 0.007 g (73%), mp: 70±81 8C.
‰aŠ ˆ ‡16:7 (c ˆ 1, H O), after 1 day À13.3; IR (Nujol)
D
2
n 1460, 1378, 1347, 1258, 1147, 1042 cmÀ1; MS, EI (m/z):

U. Eilitz et al. / Journal of Fluorine Chemistry 115 (2002) 149±154
153
‰aŠ ˆ ‡70 (c ˆ 4, CHCl ); IR (KBr) n 2987, 2878, 1786,
evaporation of the solvent 0.036 g (70%) of 11 were
obtained as a colorless oil.
D
3
1711, 1455, 1383, 1367, 1257, 1215, 1190 cmÀ1; H NMR
1
(CDCl3): d 1.40 [s, 3H, C(CH3)2], 1.61 [s, 3H, C(CH3)2], 3.50
‰aŠ ˆ ‡2:1 (c ˆ 0:42, MeOH). IR (Nujol) n 1451, 1413,
D
1340, 1247, 1149, 1084, 1041 cmÀ1; MS, EI ꢀm=z† ˆ 332
2
3
(s, 1H, OH-2), 4.00 (dd, 1H, J5a=5b ˆ 12:9 Hz, J5a=4
ˆ
ˆ
ˆ
2
3
‡
‡
‡
3:2 Hz, H-5a), 4.09 (dd, 1H, J5a=5b ˆ 12:9 Hz, J5b=4
(M À 2H2O), 303 (M À OH À CH2OH), 291 (M À
‡ ‡
3
3
1:6 Hz, H-5b), 4.33 (ddd, 1H, J4=3 ˆ 6:8 Hz, J4=5a
HCOOH À CH2OH), 97 (C5H7O2) , 55 (C3H3O) , 41
‡
3:2 Hz, J ˆ 1:6 Hz, H-4), 4.52 (d, 1H, 2J ˆ 11:6 Hz,
(C2HO) .
CH2a), 4.64 (d, 1H, J3=4 ˆ 6:8 Hz, H-3), 4.72 (d, 2J ˆ
3
11:6 Hz, CH2b), 5.19 (s, 1H, H-1), 7.26±7.36 (m, 5H, Ph);
13C NMR(CDCl3): d 25.0 (CH3), 26.4 (CH3), 58.3 (C-5), 69.0
3.3. Relative amounts of tautomeric forms at equilibrium
in D6-acetone
3
3
(d, JCF ˆ 1:8 Hz, C-3), 69.1 (d, JCF ˆ 1:8 Hz, C-3), 70.9
(CH2), 71.2 (C-4), 72.3 (td, 2J ˆ 22:1 Hz, 3JCF ˆ 2:0 Hz, C-
2), 97.4 (t, 3JCF ˆ 1:6 Hz, C-1), 109.8 (CMe2), 111.2±126.4
(C4F9), 128.4 (C-4, Ph), 128.6 (C-2, 6, h), 129.0 (C-3, 5, Ph),
136.7 (C-1, Ph). 19F NMR (CDCl3): d À48.74, À48.18,
À44.01, À43.25, À41.61 (m, 4F, CF2CF2), À40.17 (dm, 1F,
2J ˆ 295:5 Hz, CF2), À37.13 (dm, 1F, 2J ˆ 297:6 Hz, CF2),
3.3.1. a-Furanose (80%)
1
2
3
H NMR: d 3.68 (dd, 1H, J ˆ 12:7 Hz, J4=5 ˆ 4:5 Hz,
H-5) 3.86 (mÃ, H-4), 3.87 (dÃ, 2J ˆ 12:7 Hz, H-5), 4.34 (d,
1H, J3=4 ˆ 8:0 Hz, H-3), 5.52 (s, 1H, H-1); 13C NMR: d
3
60.6 (C-5), 69.9 (C-3), 80.9 (C-4), 95.5 (C-1), C-2 could not
be extracted because of low intensity; 19F NMR: d À49.33
(dm, 1F, 2J ˆ 292 Hz, CF2), À47.37 (dm, 1F, 2J ˆ 293 Hz,
‡
À3.05 (m, 3F, CF3); MS, EI (m/z): 483 (M À Me), 407
‡
‡
‡
2
(M À Bn), 349 (M À Bn À acetone), 319 (M À BnÀ
CF2), À43.51 (m, 2F, CF2), À44.30 (dm, 1F, J ˆ 298 Hz,
acetone À CH2O), 303 (M À OBn À acetone À CH2O),
CF2), À41.98 (dm, 2J ˆ 298 Hz, CF2), À3.25 (m, 3F, CF3).
‡
‡
‡
‡
‡
219 (C4F9) , 91 (C7H7) , 59 (C3H7O) , 43 (C2H3O) . Anal.
Found:C,45.69;H,3.76%.Calcd.forC19H19F9O5(498.36):C,
45.79; H, 3.84%.
3.3.2. b-Furanose (11%)
1H NMR:
d
3.77 (ddÃ, 1H, J5a=5b ˆ 12:6 Hz,
2
3J5a=4 ˆ 1:7 Hz, H-5a), 3.98 (ddÃ, 1H, J5a=b ˆ 12:6 Hz,
3J5b=4 ˆ 1:2 Hz, H-5b), 4.00 (mÃ, 1H, H-4), 4.10 (sÃ, 1H,
H-3), 4.89 (s, 1H, H-1); 19F NMR: d À49.05 (dm, 1F,
2J ˆ 292 Hz, CF2), À46.35 (dm, 1F, 2J ˆ292 Hz, CF2),
À42.97 (dm, 1F, 2J ˆ 296 Hz, CF2), À40.04 (dm, 1F,
2J ˆ 299 Hz, CF2), À38.68 (dm, 1F, 2J ˆ292 Hz, CF2),
2
3.2.5. (‡)-Benzyl-2-C-perfluorobutyl-b-L-ribopyranoside
(9)
Benzyl-3,4-O-isopropylidene-2-C-per¯uorobutyl-b-L-
ribopyranoside (8) (0.145 g, 0.3 mmol) and 60% AcOH
(5 ml) were stirred at 40±50 8C for 24 h. After evaporation
of the solvent, the remaining residue was puri®ed by crystal-
lization from THF/hexanes to give 0.12 g (90%) 9, mp: 147±
149 8C (colorless crystals).
Ã
2
À36.38 (dm, 1F, J ˆ 293 Hz, CF2), À3.25 (m , 3F, CF3).
3.3.3. a-Pyranose (<1%), b-Pyranose (9%)
‰aŠ ˆ ‡67:4 (c ˆ 0:46, acetone); IR (KBr) n 3343, 1343,
1HNMR:d3.23(dd,1H,2J5a=5b ˆ 8:6 Hz,3J5a=4 ˆ 6:1 Hz,
H-5a),3.57(dd,1H,2J5a=5b ˆ 8:6 Hz,3J5b=4 ˆ 6:1 Hz,H-5b),
4.35 (sÃ, 1H, H-3), 5.33 (sÃ, 1H, H-1), H-4 could not be
extracted; 19F NMR: d À 49:5 (dmÃ, 1F, CF2), À46.35
(dmÃ, 1F, CF2), À41.93 (dm, 1F, 2J ˆ 291 Hz, CF2),
À41.18 (dm, 1F, 2J ˆ 294 Hz, CF2), À37.80 (dm, 1F,
2J ˆ 291 Hz, CF2), À35.08 (dm, 1F, 2J ˆ295 Hz, CF2),
À3.25 (mÃ, 3F, CF3); (Ã Resonance signals are overlapping).
D
1267, 1201, 1183, 1145, 1099, 1061 cmÀ1; 1H NMR(CDCl3):
2
3
d 3.83 (dd, 1H, J5a=5b ˆ 12:6 Hz, J5a=4 ˆ 1:4 Hz, H-5a),
4.05(d, 1H, 2J5a=5b ˆ 12:6 Hz, H-5b), 4.13(m, 1H, H-4), 4.24
(d, 1H, 3J3=4 ˆ 3 Hz, H-3), 4.58 (d, 1H, 2J ˆ 11:6 Hz, CH2a),
4.81(d,1H,2J ˆ 11:6 Hz,CH2b),5.11(s,1H,H-1),7.36±7.42
(m, 5H, Ph); 13C NMR (CDCl3): d 63.5 (C-5), 64.7 (C-3), 70.0
(CH2), 71.3 (C-4), 79.5 (t, 2JCF ˆ 22:1 Hz, C-2), 99.9 (C-1),
110±126(C4F9),128.2(C-2,4,6,Ph),128.8(C-3,5,Ph),137.8
(C-1, Ph); 19F NMR (CDCl3): d À48.58 (dm, 1F, 2J ˆ
291:3 Hz, CF2), À46.21 (dm, 1F, 2J ˆ 294:6 Hz, CF2),
À42.99 (dm, 1F, 2J ˆ 288:3 Hz, CF2), À40.96 (dm, 1F,
2J ˆ 288:5 Hz, CF2), À37.23 (d, 1F, 2J ˆ 291:8 Hz),
Acknowledgements
The authors are grateful to the European Community
(TMR: Contract no. ERBFMRXCT 970 120: ``Fluorine:
A Unique Tool for Engineering Molecular Properties''), the
Deutsche Forschungsgemeinschaft and the Fonds der Che-
mischen Industrie for ®nancial support.
2
À34.82 (ddt, 1F, J ˆ 294:6 Hz, J ˆ 21:5 Hz, J ˆ 14 Hz,
‡
CF2), À3.0 (m, 3F, CF3); MS, EI ꢀm=e† ˆ 351 (M À Bn),
‡
‡
321 (M À Bn À CH2O), 219 (C4F9) , 91 (C7H7), 43
‡
(C2H3O) .
3.2.6. (‡)-2-C-Perfluorobutyl-L-ribose (11)
A solution of benzyl-2-C-per¯uorobutyl-b-L-ribopyrano-
side (9) (0.07 g, 0.15 mmol) in dry MeOH (5 ml) was stirred
in the presence of a Pd/C catalyst in an atmosphere of
hydrogen until the starting material was completely con-
sumed (4 weeks, 19F NMR analysis). After ®ltration and
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