Organofluorine compounds and fluorinating agents; 20:1 The nucleophilic perfiuoroalkylation of sugar aldehydes using a sonochemical barbier-type reaction

Article abstract of DOI:10.1055/s-1998-2101

A convenient synthesis of C-perfluoroalkylated carbohydrates 2a-c and 3a-c based on a sonochemical Zn-mediated reaction of the sugar aldehyde 1 with perfluoroalkyl iodides (C₄F₉I, C₆F₁₃I, C₈F₁₇I) has been developed. Stirring or reflux at 120°C gives no detectable products and hence the application of ultrasound is crucial. The obtained carbohydrate derivatives were stepwise deprotected (intermediates 6a-c) to the amphiphilic mesogenic compounds 7a-c consisting of a sugar moiety with free hydroxyl groups and a perfluoroalkyl tail directly attached to a sugar carbon. Moreover, the amphiphiles 7a-c were peracetylated to the furanose 8 and the pyranose 9, respectively.

Full text of DOI:10.1055/s-1998-2101

SYNTHESIS
July 1998
1033
Organofluorine Compounds and Fluorinating Agents; 20:1 The Nucleophilic
Perfluoroalkylation of Sugar Aldehydes Using a Sonochemical Barbier-Type Reaction
Dietmar Peters, Cornelia Zur, Ralf Miethchen*
Fachbereich Chemie, Universität Rostock, Buchbinderstraße 9, D-18051 Rostock, Germany
Fax +49(381)4981819; E-mail: ralf.miethchen@chemie.uni-rostock.de
Received 28 October 1997; revised 27 January 1998
Abstract: A convenient synthesis of C-perfluoroalkylated carbo-
hydrates 2a–c and 3a–c based on a sonochemical Zn-mediated
reaction of the sugar aldehyde 1 with perfluoroalkyl iodides
alkylations. Cavitational effects result in cleaning of
(C4F9I, C6F13I, C8F17I) has been developed. Stirring or reflux at
120˚C gives no detectable products and hence the application of
found that ultrasonic agitation is suitable to shorten the re-
action time and to increase the yield in such perfluoro-
surfaces and the erosion of solids.15 Moreover, ultrasound
promotes reactions on metal surfaces owing to cavitation.
ultrasound is crucial. The obtained carbohydrate derivatives were
stepwise deprotected (intermediates 6a–c) to the amphiphilic
mesogenic compounds 7a–c consisting of a sugar moiety with
free hydroxyl groups and a perfluoroalkyl tail directly attached to
a sugar carbon. Moreover, the amphiphiles 7a–c were peracetyl-
ated to the furanose 8 and the pyranose 9, respectively.
We report here the perfluoroalkylation of 3-O-ben-
zyl-1,2-O-isopropylidene-α-D-xylopentodialdo-1,4-fura-
nose (1)16,17 with perfluorobutyl, perfluorohexyl or per-
fluorooctyl iodide in the presence of zinc (solvent:
DMF). In the course of each reaction two diastereomeric
products were formed, i.e. the epimers 2a/3a, 2b/3b and
2c/3c. The crystalline (5R)-diastereomers 2a, 2b, and 2c
could be chromatographically separated from the corre-
sponding syrupy (5S)-diastereomers 3a, 3b, and 3c
(Scheme 1, Table 2). The ratios of the corresponding
(5R)- to (5S)-epimers were after the chromatographic
separation 2.1 : 1 (2a/3a), 3.2 : 1 (2b/3b), and 2.3 : 1 (2c/
3c), respectively.
Key words: carbohydrates, amphiphiles, mesogens, perfluoro-
alkylation, ultrasound
Perfluoroalkylated monosaccharides which contain the
strongly hydrophobic perfluoroalkyl chain and a biocom-
patible polar head group should be useful surfactants and
emulsifiers for biomedical applications.2 The sugar moi-
ety may allow specific in vivo recognition and hence such
substances may be capable of drug targeting.3 On the oth-
er hand, such amphiphilic compounds may have interest-
ing liquid-crystalline properties; however, mesogenic
properties of perfluoroalkylated carbohydrate am-
phiphiles have not been described so far.
Perfluoroalkyl halides are readily available and reactive
reagents for the nucleophilic introduction of perfluoro-
alkyl chains into organic molecules.4 Recently, we report-
ed on two methods of introducing perfluoroalkyl chains
into carbohydrates, namely the dithionite-catalyzed addi-
tion of perfluoroalkyl iodides to unsaturated
carbohydrates1 and the non-conventional acetalation of
pyranosides with perfluoroalkanals.5,6 A further method
presented in this paper is aimed at the synthesis of am-
phiphilic perfluoroalkyl substituted carbohydrates with a
stable C–C bond between the sugar moiety and the per-
fluoroalkyl tail.
i) RFI/Zn/DMF, sonication, r.t., 1.5–8 h; ii) Ac2O/pyridine, r.t., 12 h
Numerous publications describe fluorinated organometal-
lics as synthetic intermediates for the perfluoroalkylation
of organic molecules (References 4, 7 and literature cited
therein). Thus, perfluoroalkyltrimethylsilanes8,9 and per-
fluoroalkylmagnesium reagents10 have been used for that
purpose. Because the latter are rather unstable, it is
favourable to generate these reagents in situ by a metal-
halogen-exchange reaction.4,11 Portella at al.12 have used
these reagents in carbohydrate chemistry.
Scheme 1
The influence of ultrasonic agitation on the outcome of
the reaction was tested under several reaction conditions
(Table 1). Hardly any product could be detected by stir-
ring at room temperature or at 120°C, even after using
prolonged reaction times. The overall yields were higher
The in situ generation of an organometallic reagent in the with the shorter chain perfluoroalkyl iodides and in-
presence of the substrate (Barbier-type reactions) has creased with the sound intensity in the investigated range.
been applied for perfluoroalkylations with fluoro-substi- Thus, in a 35 kHz ultrasonic cleaning bath the yield was
tuted organozinc reagents.13,14 Kitazume and Ishikawa13 much better than under stirring; with a 850 kHz focused

SYNTHESIS
Papers
1034
Table 2. Compounds 2a–c, 3a–c, 4c, 5c, 6a–c, 7a–c, 8, and 9 Prepared
high-frequency bath it increased somewhat. However, the
experimental data are not sufficient to give a general state-
ment on the frequency effect. The best yields could be ob-
tained with a 20 kHz probe system, where the ultrasonic
transducer can be directly immersed into the reaction mix-
ture and which is much more intensive than a cleaning
bath system. It is not possible to increase the power input
beyond a certain value because decoupling occurs and the
sonochemical effect decreases sharply.18 For the reaction
a reactor system was used which allowed the immersion
of the transducer under argon and intensive cooling at the
same time.18
Sub-
Prod-
Yield
g (%)
mp (°C)
(solvent)
[α]D22
Rfc
strate ucta
(c)b
1
1
1
2a
3a
1.79
(36)
0.85
(17)
56–58
(hexane)
syrup
–31.9
(1.24)
–29.8
(1.12)
0.66
0.74
2b
3b
2.27
(38)
0.72
(12)
59–60
(hexane)
syrup
–26.5
(1.17)
–24.9
(1.19)
0.57
0.66
2c
3c
1.85
(26.5)
0.87
84–85
(heptane)
syrup
–23.2
(1.01)
–21.7
(1.07)
0.55
0.64
Table 1. Overall Yields in the Nucleophilic Perfluoroalkylations of 1
with Perfluoroalkyl Iodides Depending on the Reaction Conditions
(12.5)
2c
3c
2a
2b
2c
6a
6b
6c
7b
4c
5c
6a
6b
6c
7a
7b
7c
0.44
(95)
65–67
(heptane)
–9.4
(1.10)
0.55d
0.69d
0.41
Conditions
Yield (%)
0.37
(88)
70–71
(heptane)
–18.2
(1.12)
2a and 3aa 2b and 3bb 2c and 3cc
0.61
(90)
120–124
(hexane/EtOAc)
–5.1
(1.12)
stirring; r.t.
stirring; 120°C
ultrasonic bath; 35 kHz
ultrasonic probe; 20 kHz, 120 W 53
ultrasonic probe; 20 kHz, 60 W
ultrasonic bath; 850 kHz
7
–
<1
<1
20
39
–
–
<1
22
50
35
–
1.2
(85)
130–131
(hexane/EtOAc)
–6.2
(1.09)
0.30
35
–
0.59
(87)
143–145
(hexane/EtOAc)
145–148f
(heptane/acetone)
163–166f
(heptane/acetone)
174–176f
(heptane/acetone)
–10.1
0.22
(1.03)e
43
–
0.24
(75)
–
–
–
0.41g
0.36g
0.30g
a Reaction time 1.5 h.
b Reaction time 3 h.
c Reaction time 8 h.
0.92
(88)
0.21
(92)
The structures of the products 2a–c and 3a–c are support-
0.59h
0.51h
1
ed by their H, 13C, and 19F NMR spectra, respectively.
8
9
0.05
(22)
0.09
(37)
syrup
–26.8
(1.14)
+49.0
(0.50)
Thus, the perfluoroalkyl chain is represented by 19F sig-
syrup
nals for the CF2-groups in the range of δ = –127 to –105
and the signal for the CF3-group at about – 80. In the 13
C
a
Satisfactory microanalyses obtained: C ± 0.33, H ± 0.21 (Exception:
NMR spectra of the compounds the signals for the C-5
carbon atoms appear as double doublets with coupling
constants of about 22 and 29 Hz, because of their coupling
with the neighbouring F-atoms. Because the J4,5 coupling
constants of 2a–c and 3a–c were not exactly observable in
3c, C –0.57).
CHCl3.
Toluene/EtOAc (3:1).
Heptane/EtOAc (5:1).
b
c
d
e
f
Acetone.
1
Clearing points: 7a, 126–137°C (SA-phase, monotropic), 7b,
159–168°C (SA-phase, enantiotropic), 7c, 188–192°C (SA-phase,
enantiotropic).
Toluene/EtOAc (1:2).
Heptane/EtOAc (1:1).
the H NMR spectra owing to overlapping signals, the
epimers 2c and 3c were acetylated to 4c and 5c, respec-
tively (Scheme 1). The relatively small J4,5 couplings of
4c (3.1 Hz) indicate a (5R) configuration, the large J4,5
couplings of 5c (12.2 Hz) correlate with a (5S) configura-
tion. In addition, the NOESY-spectrum of the derivative
3a recorded in DMSO-d6 did show weak cross peaks
g
h
between the OH-proton in position 5 and the H-3 as well reduces significantly the reactivity of the benzylic ether
as between the H-1 and H-5 protons expected for a (5R) function. In comparison the isopropylidene moiety could
configuration. Consequently, the minor products 3a–c are be removed without difficulties yielding the fully depro-
D-gluco configurated and the major diastereomers 2a–c tected 5-C-(perfluoroalkyl)-D-xyloses 7a–c (Scheme 2,
are L-ido configurated. To support this stereochemical as- Table 2). It is noticeable that these amphiphilic products
signment additionally, NMR data of 5-C-substituted (non- are liquid crystals forming smectic A phases. The thermal
fluorinated) 3-O-methyl- and 3-O-benzyl-1,2-O-isopro- behaviour was investigated by polarising microscopy and
pylidene-L-ido- and D-glucofuranoses reported in the lit- DSC measurements (for more details see Ref. 21).
erature were used.19,20
The NMR data of the three amphiphilic L-idoses 7a–c cor-
The debenzylation of 2a–c to 6a–c by hydrogenation in respond as expected in various details with the published
the presence of palladium on charcoal required fairly long 1H22,23 and 13C NMR data23,24 of D-idose. However, be-
α/β-pyranose and
reaction times, i.e. the neighbouring perfluoralkyl group cause of the overlapping of numerous

SYNTHESIS
July 1998
1035
Table 3. Composition of the Pyranose/Furanose Mixtures of the Am-
phiphiles 7a–c in Acetone-d6
Prod- Anomeric
Concen-
tration (%)
δ (H-1)a J1,2 (Hz) δ (C-1)b
uct
form
7a
α-pyranose
β-pyranose
α-furanose
β-furanose
α-pyranose
β-pyranose
α-furanose
β-furanose
α-pyranose
β-pyranose
α-furanose
β-furanose
12.0
29.2
24.0
34.8
12.1
29.5
22.0
36.3
20.7
26.7
20.3
32.3
5.12
5.01
5.36
5.15
5.15
5.04
5.38
5.18
5.14
5.03
5.37
5.17
≈1
≈1
4.3
1.8
1.2
<1
4.3
1.4
1.2
<1
4.3
1.6
96.0
93.6
96.1
102.6
96.0
93.6
96.1
102.6
95.7
93.2
95.7
102.1
7b
7c
a 1H NMR (250 MHz).
b 13C NMR (62 MHz).
i) H2/Pd-C/EtOH/MeOH, r.t. 70–96 h; ii) 90% TFA, r.t., 6–20 h
Scheme 2
α/β-furanose signals the 1H and 13C NMR spectra of the
amphiphiles 7a–c could not be evaluated in detail. The 1H
NMR spectra of 7a–c recorded in acetone-d6/D2O show
the existence of the anomeric pyranose and furanose
forms by displaying four different H-1 signals (Table 3).
To assign these signals, first of all the corresponding C-1
signals were evaluated by comparison of the 13C NMR
spectra of 7a–c with the C-1 data of the four anomeric D-
idoses (furanoses α/β:δ = 103.1/96.8; pyranoses α/β:δ =
94.4/93.7).23 The chemical shifts and splittings of the ano-
meric protons of 7a–c assigned by a 1H,13C-COSY exper-
iment using the C-1 data correspond to those of the D-
idofuranoses (α:δ = 5.19, J1,2 = 1.3 Hz; β:δ = 5.41, J1,2 = 4.3
Hz) and D-idopyranoses (α:δ = 4.97, J1,2 = 6.0 Hz; β:δ =
5.05, J1,2 = 1.6 Hz) as well.22,23 Integration of the H-1 sig-
nals shows that in acetone-d6/D2O the amount of furanoses
Scheme 3
9 correspond to an α-L-ido-diastereomer which adopts a
distorted boat conformation (b0.3). In such a conforma-
tion, the relatively stiff perfluoroalkyl chain as well as the
acetyl groups in 1-, 2-, and 3-position are quasi-equatori-
ally arranged. Therefore, the H-2, H-3 and H-4 ring pro-
tons are approximately trans-diaxial oriented to each
other which is indicated by relatively large coupling con-
stants (J2,3 ≈ 7.6 Hz, J3,4 ≈ 7.5 Hz). The coupling constants
J1,2 ≈ 4.5 Hz and J4,5 ≈ 2.9 Hz are also in good agreement
with the assumed conformation of 9. Additionally, the
chemical shift of δ = 6.45 indicates an equatorial position
is unusually high (Table 3). However, this result is not sur-
25,26
prising for ido-configurated sugars since Angyal
has
observed high concentration of furanoses (25–32%) in the
equilibrium of unprotected D-idose as well. Both the pyr-
anose forms have such unfavourable interactions that the
furanoses, although also disfavoured, become important
contributors to the equilibrium.25 In the case of 7a–c, the
perfluoroalkyl chains seem to favour additionally the
furanose form (see also Ref. 21).
To support the L-ido configuration of the diastereomers for the H-1, corresponding to an α-L-ido configuration.
2a–c, 6a–c, and 7a–c, the unprotected sugar 7b was sub-
In summary the generation of the L-ido-products 2a–c is
jected to acetylation (Scheme 3). Two main products, 8
significantly favoured over the corresponding D-gluco-
and 9, were separated and characterized by NMR-spectro-
epimers 3a–c in sonochemical Zn-mediated nucleophilic
scopic investigations. For the furanose 8 no coupling was
additions of 1-iodoperfluoroalkanes to the sugar alde-
observable between H-1 and H-2, the coupling constant
hyde 1. Furthermore, it is noticeable that the equilibrium
between H-2 and H-3 was likewise very small (1.6 Hz) in-
mixtures of the amphiphilic 5-C-perfluoroalkylated sug-
dicating the β-furanose configuration.
ars 7a–c contain unusually high parts of the anomeric
As expected, the H-4,H-5-coupling constant of the pyra- furanoses and that the corresponding pyranoses prefer a
nose 9 (J4,5 ≈ 2.9 Hz) does not correspond to a D-gluco- conformation between 4C1 and 1C4 with a quasi-equato-
4
derivative which should adopt a C1-conformation and rial arrangement of the perfluoroalkyl chain (see also
give a significantly larger J4,5 value. The 1H NMR data of Ref. 21).

SYNTHESIS
Papers
1036
Solvent systems are given in v/v. 1H and 13C {1H} NMR: Bruker AC
250; internal standard TMS, J values in Hz. 19F {1H} NMR: external
standard CFCl3. To acetone-d6 as NMR solvent three drops of D2O
were added. TLC: silica gel foils 60 F254 (Merck). Column chroma-
tography: silica gel 60 (63–200 µm) (Merck). Melting points: Polaris-
ing microscope Leitz Laborlux 12 Pol equipped with a hot stage
Mettler FP 90. Sonications were performed with a) ultrasonic bath,
Bandelin Sonorex 102 H, 35 kHz; 2 × 120 W electrical power input;
2a:
1H NMR (250 MHz, CDCl3): δ = 1.25, 1.41 (s, 3 H, CH3), ≈ 3.13 (br,
1 H, OH), 4.00 (m, 1 H, H-3), 4.40 (m, 1 H, H-4), 4.43 (d, 1 H, J =
11.5 Hz, CH2Ph), 4.47 (m, 1 H, H-5), 4.55 (d, 1 H, J1,2 = 4.0 Hz, H-
2), 4.61 (d, 1 H, CH2Ph), 5.91(d, 1 H, J1,2 = 4.0 Hz, H-1), 7.19–7.31
(m, 5 H, C6H5).
13C NMR (62 MHz, CDCl3) : δ = 26.3, 26.8 (CH3), 67.6 (dd, JC-5,F
=
21.5 Hz, JC-5,F’ = 29.3 Hz, C-5), 72.4 (CH2Ph), 75.7 (C-4), 82.0 (C-2),
83.2 (C-3), 105.0 (C-1), 112.6 [C(CH3)2], 105–120 (m, 3 CF2, CF3),
127.9, 128.4, 128.7, 136.4 (C6H5).
b) immersion probe, Vibracell VX 400, 20 kHz, probe
13 mm,
120 W (setting 30%) or 60 W (setting 15%) electrical power input; c)
ultrasonic bath, UST Meinhardt, K 80/5, 850 kHz, focus transducer,
100 W (power setting 4) electrical power input.
19F NMR (235 MHz, CDCl3): δ = –127.6 to –124.2 (m, 3 F, CF2),
–122.7 to –122.6 (m, 2 F, CF2), –120.3 to –119.0 (m, 1 F, CF2CH2),
–80.7 (CF3).
MS (70 eV): m/z = 499 (M+ + H).
3a:
Perfluoroalkylation of 1; General Procedure A:
To a solution of 117 (2.78 g, 10 mmol) in anhyd DMF (15 mL) was
added zinc dust (1.34 g, 20 mmol) under an argon atmosphere. Then
the mixture was sonicated (immersion probe, electrical power input
120 W/setting 30%) and the corresponding perfluoroalkyl iodide
(20 mmol) was added. After a short induction period the reaction be-
came strongly exothermic and decoupling may occur. In this case the
sonication had to be switched off for some minutes. When the starting
material had disappeared (TLC control, eluent: toluene/EtOAc, 3:1),
the reaction mixture was poured into 2% aq HCl (50 mL). After ex-
traction with Et2O (100 mL) the separated organic phase was succes-
sively washed with satd aq solution of NH4Cl (50 mL), a 10% aq
solution of Na2S2O3 (50 mL), and brine (50 mL). The Et2O phase was
dried (Na2SO4), filtered and concentrated under reduced pressure.
Subsequently, the syrupy residue was purified by column chrom-
atography (eluent: toluene/EtOAc, 15:1).
1H NMR (250 MHz, CDCl3): δ = 1.26, 1.42 (s, 3 H, CH3), 4.22 (m, 3
H, H-3, H-5, OH), 4.30 (m, 1 H, H-4), 4.48 (d, 1 H, J = 11.0 Hz,
CH2Ph), 4.56 (d, 1 H, J1,2 = 3.7 Hz, H-2), 4.60 (d, 1 H, J = 11.0 Hz,
CH2Ph), 5.94 (d, 1 H, J1,2 = 3.7 Hz, H-1), 7.18–7.34 (m, 5 H, C6H5).
13C NMR (62 MHz, CDCl3) : δ = 26.1, 26.6 (CH3), 69.9 (dd, JC-5,F
=
21.9 Hz, JC-5,F’ = 25.8 Hz, C-5), 72.8 (CH2Ph), 74.8 (C-4), 81.8 (C-2),
84.7 (C-3), 104.6 (C-1), 112.2 [C(CH3)2], 105 –120 (m, 3 CF2, CF3),
128.2, 128.7, 128.8, 135.8 (C6H5).
19F NMR (235 MHz, CDCl3): δ = –127.6 to – 123.9 (m, 3 F, CF2),
–122.7 to –122.4 (m, 2 F, CF2), –120.0 to –118.7 (m, 1 F, CF2CH2),
–80.7 (CF3).
MS (70 eV): m/z = 499 (M+ + H).
(5R)-3-O-Benzyl-1,2-O-isopropylidene-5-C-perfluorohexyl-α-D-xy-
lofuranose (2b) and (5S)-3-O-Benzyl-1,2-O-isopropylidene-5-C-per-
fluorohexyl-α-D-xylofuranose (3b): Compound 117 (2.78 g, 10 mmol)
was reacted with perfluorohexyl iodide (8.92 g, 4.3 mL, 20 mmol) ac-
cording to the general procedure A (reaction time: 3 h). After column
chromatographic separation the crystalline 5R-product 2b and the
syrupy 5S-product 3b were isolated (Table 2).
Acetylation of 2a–c; General Procedure B (cf. Ref. 27):
To an ice cooled solution of the sugar 2 (1.0 mmol) in Ac2O (1.5 mL)
was added pyridine (1.5 mL) and the mixture was allowed to warm up
to r.t. and allowed to stand overnight. After addition of Et2O (10 mL),
the organic phase was separated and washed with satd aq citric acid
solution (2 × 5 mL), satd aq NH4Cl solution (5 mL), and brine (5 mL).
Then, the organic phase was dried (Na2SO4), filtered and concen-
trated under reduced pressure. Traces of pyridine were removed by
co-distillation with CHCl3/toluene (7:3). The residue was purified by
column chromatography (eluent: heptane/EtOAc, 5:1).
2b:
1H NMR (250 MHz, CDCl3): δ = 1.25, 1.41 (s, 3 H, CH3), ≈ 3.14 (br,
1 H, OH), 4.00 (m, 1 H, H-3), 4.40 (m, 1 H, H-4), 4.43 (d, 1 H, J =
11.3 Hz, CH2Ph), 4.47 (m, 1 H, H-5), 4.56 (d, 1 H, J1,2 = 3.7 Hz, H-
2), 4.61 (d, 1 H, J = 11.3 Hz, CH2Ph), 5.91(d, 1 H, J1,2 = 3.7 Hz, H-
1), 7.20–7.30 (m, 5 H, C6H5).
13C NMR (62 MHz, CDCl3) : δ = 26.3, 26.8 (CH3), 67.6 (dd, JC-5,F
=
21.0 Hz, JC-5,F’ = 29.7 Hz, C-5), 72.4 (CH2Ph), 75.7 (C-4), 82.0 (C-2),
83.1 (C-3), 104.9 (C-1), 112.6 [C(CH3)2], 105 –120 (m, 5 CF2, CF3),
128.4, 128.6, 128.9, 136.4 (C6H5).
Debenzylation of 2a–c; General Procedure C (cf. Ref. 28):
3-O-Benzyl derivative 2a, 2b, or 2c (1.0 mmol) was dissolved in
EtOH/MeOH 1:1 (5 mL), 10% Pd/C (0.03 g) was added and the mix-
ture stirred under H2 at r.t. until the starting material had disappeared.
After filtration and evaporation of the solvents under reduced pres-
sure, the obtained white solid was purified by column chromatogra-
phy and/or recrystallization.
19F NMR (235 MHz, CDCl3): δ = –127.2 to –124.4 (m, 3 F, CF2),
–122.6 to –121.7 (m, 6 F, CF2), –120.1 to – 118.9 (m, 1 F, CF2CH2),
–80.6 (CF3).
MS (CI-isobutane): m/z = 599 (M+ + H).
3b:
1H NMR (250 MHz, CDCl3): δ = 1.26, 1.42 (s, 3 H, CH3), 4.29 (m, 3
H, H-3, H-5, OH) 4.38 (m, 1 H, H-4), 4.56 (d, 1 H, J = 11.0 Hz,
CH2Ph), 4.64 (d, 1 H, J1,2 = 3.7 Hz, H-2), 4.68 (d, 1 H, J = 11.0 Hz,
CH2Ph), 5.94 (d, 1 H, J1,2 = 3.7 Hz, H-1), 7.20–7.30 (m, 5 H, C6H5).
Deisopropylidenation of 6a–c; General Procedure D (cf. Ref. 29):
The 1,2-O-isopropylidene derivative 6a, 6b, or 6c (0.5 mmol) was
dissolved in 90% TFA (5 mL) and the mixture was stirred at r.t. until
the starting material had disappeared (approx. 6–20 h; monitored by
TLC). Then the mixture was codistilled under reduced pressure in a
rotary evaporator with toluene (3 or 4 × 10 mL) in order to remove
TFA and H2O. The residue was purified by chromatography and/or
recrystallization.
13C NMR (62 MHz, CDCl3) : δ = 26.1, 26.6 (CH3), 70.0 (dd, JC-5,F
=
22.0 Hz, JC-5,F’ = 26.7 Hz, C-5), 72.8 (CH2Ph), 74.8 (C-4), 81.8 (C-2),
84.7 (C-3), 104.6 (C-1), 112.2 [C(CH3)2], 105–120 (m, 5 CF2, CF3),
128.2, 128.7, 128.9, 135.8 (C6H5).
19F NMR (235 MHz, CDCl3): δ = –126.1 to –125.0 (m, 3 F, CF2),
–122.4 to –121.5 (m, 6 F, CF2), –119.8 to –118.6 (m, 1 F, CF2CH2),
–80.5 (CF3).
(5R)-3-O-Benzyl-1,2-O-isopropylidene-5-C-perfluorobutyl-α-D-xy-
lofuranose (2a) and (5S)-3-O-Benzyl-1,2-O-isopropylidene-5-C-per-
fluorobutyl-α-D-xylofuranose (3a): Compound 117 (2.78 g, 10 mmol)
was reacted with perfluorobutyl iodide (6.92 g, 3.4 mL, 20 mmol) ac-
cording to the general procedure A (reaction time: 1.5 h). After col-
umn chromatographic separation, the crystalline 5R-product 2a and
the syrupy 5S-product 3a were isolated (Table 2).
MS (CI-isobutane): m/z = 599 (M++H).
(5R)-3-O-Benzyl-1,2-O-isopropylidene-5-C-perfluorooctyl-α-D-xy-
lofuranose (2c) and (5S)-3-O-Benzyl-1,2-O-isopropylidene-5-C-per-
fluorooctyl-α-D-xylofuranose (3c): Compound 117 (2.78 g, 10 mmol)
was reacted with perfluorooctyl iodide (10.92 g, 20 mmol), dissolved

SYNTHESIS
July 1998
1037
in anhyd DMF (2 mL) according to the general procedure A (reaction
time: 8 h). After column chromatographic separation, the crystalline
5R-product 2c and the syrupy 5S-product 3c were isolated (Table 2).
2c:
(5R)-1,2-O-Isopropylidene-5-C-perfluorobutyl-α-D-xylofuranose
(6a): Compound 2a (0.83 g, 1.66 mmol) was debenzylated according
to the general procedure C (reaction time: 96 h). The residue was
crystallized from hexane/EtOAc (colourless needles) (Table 2).
1H NMR (250 MHz, acetone-d6): δ = 1.29, 1.43 (s, 3 H, CH3), 4.32
(m, 1 H, H-3), 4.39 (m, 1 H, H-4), 4.57 (d, 1 H, J1,2 = 3.5 Hz, H-2),
4.70 (dddd, 1 H, J5,F = 22.7 Hz, J5,F’ = 3.5 Hz, J5,OH = 1.8 Hz, H-5), ≈
4.9 (br, 2 H, OH), 5.95 (d, 1 H, J1,2 = 3.5 Hz, H-1).
1H NMR (250 MHz, CDCl3): δ = 1.25, 1.41 (s, 3 H, CH3), ≈ 3.16 (br,
1 H, OH), 4.00 (m, 1 H, H-3), 4.40 (m, 1 H, H-4), 4.42 (d, 1 H, J =
11.6 Hz, CH2Ph), 4.47 (m, 1 H, H-5), 4.56 (d, 1 H, J1,2 = 3.7 Hz, H-
2), 4.61 (d, 1 H, J = 11.6 Hz, CH2Ph), 5.91 (d, 1 H, J1,2 = 3.7 Hz, H-
1), 7.18–7.30 (m, 5 H, C6H5).
13C NMR (62 MHz, acetone-d6): δ = 26.6, 27.3 (CH3), 68.5 (dd, JC-5,F
= 20.8 Hz, JC-5,F´ = 28.6 Hz, C-5), 76.5 (d, JC-3,F = 3.7 Hz, C-3), 77.5
(C-4), 86.6 (C-2), 105.6 (C-1), 112.5 [C(CH3)2], 110–122 (m, 3 CF2,
CF3).
13C NMR (62 MHz, CDCl3) : δ = 26.3, 26.8 (CH3), 67.6 (dd, JC-5,F
=
21.5 Hz, JC-5,F’ = 28.7 Hz, C-5), 72.4 (CH2Ph), 75.8 (C-4), 82.1 (C-2),
83.2 (C-3), 104.9 (C-1), 112.6 [C(CH3)2], 105 –120 (m, 7 CF2, CF3),
128.2, 128.7, 129.0, 136.5 (C6H5).
19F NMR (235 MHz, acetone-d6): δ= –128.2 to –124.4 (m, 3 F, CF2),
–123.1, –122.7 (s, 1 F, CF2), –119.7 to –118.5 (m, 1 F, CF2CH2),
–81.6 (CF3).
19F NMR (235 MHz, CDCl3): δ = –126.2 to –125.0 (m, 3 F, CF2),
–122.5 to –121.7 (m, 10 F, CF2), –120.1 to – 118.9 (m, 1 F, CF2CH2),
–80.7 (CF3).
MS (CI-isobutane): m/z = 699 (M+ + H).
(5R)-1,2-O-Isopropylidene-5-C-perfluorohexyl-α-D-xylofuranose
(6b): Compound 2b (1.64 g, 2.74 mmol) was debenzylated according
to the general procedure C (reaction time: 70 h). The residue was
crystallized from hexane/EtOAc (Table 2).
3c:
1H NMR (250 MHz, CDCl3): δ = 1.26, 1.42 (s, 3 H, CH3), 4.20 (m, 3
H, H-3, H-5, OH), 4.31 (m, 1 H, H-4), 4.49 (d, 1 H, J = 11.0 Hz,
CH2Ph), 4.56 (d, 1 H, J1,2 = 3.7 Hz, H-2), 4.60 (d, 1 H, J = 11.0 Hz,
CH2Ph), 5.95 (d, 1 H, J1,2 = 3.7 Hz, H-1), 7.20–7.31 (m, 5 H, C6H5).
1H NMR (250 MHz, acetone-d6): δ = 1.29, 1.43 (s, 3 H, CH3), 4.32
(m, 1 H, H-3), 4.39 (m, 1 H, H-4), 4.57 (d, 1 H, J1,2 = 3.8 Hz, H-2),
4.63–4.79 (m, 1 H, H-5), ≈ 4.86 (br, 1 H, OH), ≈ 4.98 (br, 1 H, OH),
5.95 (d, 1 H, J1,2 = 3.8 Hz, H-1).
13C NMR (62 MHz, CDCl3) : δ = 26.1, 26.6 (CH3), 69.9 (dd, JC-5,F
=
22.5 Hz, JC-5,F’ = 25.8 Hz, C-5), 72.8 (CH2Ph), 74.8 (C-4), 81.8 (C-2),
84.7 (C-3), 104.6 (C-1), 112.1 [C(CH3)2], 105 –120 (m, 7 CF2, CF3),
128.2, 128.7, 128.8, 135.8 (C6H5).
13C NMR (62 MHz, acetone-d6): δ = 26.6, 27.3 (CH3), 68.6 (dd, JC-5,F
=
21.6 Hz, JC-5,F’ = 28.1 Hz, C-5), 76.6 (d, JC-3,F = 4.0 Hz, C-3), 77.6 (C-4),
86.6 (C-2), 105.7 (C-1), 112.5 [C(CH3)2], 105–122 (m, 5 CF2, CF3).
19F NMR (235 MHz, acetone-d6): δ = –127.9 to –125.1 (m, 3 F, CF2),
–123.1, –122.8, –122.5 (s, 1 F, CF2), –122.0 (s, 3 F, CF2), –119.6 to
–118.4 (m, 1 F, CF2CH2), –81.4 (CF3).
19F NMR (235 MHz, CDCl3): δ = –127.8 to –124.8 (m, 3 F, CF2),
–123.6 to –121.6 (m, 10 F, CF2), –117.9 to –116.7 (m, 1 F, CF2CH2),
–81.3 (CF3).
(5R)-5-O-Acetyl-3-O-benzyl-1,2-O-isopropylidene-5-C-perfluorooc-
tyl-α-D-xylofuranose (4c): Compound 2c (0.43 g, 0.62 mmol) was
acetylated with Ac2O/pyridine as described in the general procedure
B. After column chromatographic separation (Rf = 0.55, eluent: hep-
tane/EtOAc, 5 : 1), the crystalline product 4c was isolated (Table 2).
1H NMR (250 MHz, CDCl3): δ = 1.31, 1.50 (s, 3 H, CH3), 2.04 (s, 3
H, COCH3), 4.03 (dd, 1 H, J3,4 = 3.7 Hz, J4,5 = 3.1 Hz, H-4), 4.48 (d,
1 H, J = 11.3 Hz, CH2Ph), 4.51 (dd, 1 H, J2,3 = 8.5 Hz, H-3), 4.62 (d,
1 H, J = 11.3 Hz, CH2Ph), 4.62 (dd, 1 H, J1,2 = 4.0 Hz, H-2), 5.90 (d,
1 H, J1,2 = 4.0 Hz, H-1), 6.15 (ddd, 1 H, J5,F = 20.0 Hz, J5,F’ = 8.4 Hz,
H-5), 7.26–7.39 (m, 5 H, C6H5).
(5R)-1,2-O-Isopropylidene-5-C-perfluorooctyl-α-D-xylofuranose
(6c): Compound 2c (0.78 g, 1.11 mmol) was debenzylated according
to the general procedure C (reaction time: 84 h). The residue was
crystallized from hexane/EtOAc (Table 2).
1H NMR (250 MHz, acetone-d6): δ = 1.29, 1.43 (s, 3 H, CH3), 4.33
(m, 1 H, H-3), 4.39 (m, 1 H, H-4), 4.57 (d, 1 H, J1,2 = 3.7 Hz, H-2),
4.62–4.78 (m, 1 H, H-5), ≈ 4.84 (br, 1 H, OH), ≈ 4.97 (br, 1 H, OH),
5.95 (d, 1 H, J1,2 = 3.7 Hz, H-1).
13C NMR (62 MHz, acetone-d6): δ = 26.6, 27.3 (CH3), 68.6 (dd, JC-5,F
= 21.7 Hz, JC-5,F’ = 28.1 Hz, C-5), 76.6 (d, JC-3,F = 4.0 Hz, C-3), 77.6
(C-4), 86.6 (C-2), 105.7 (C-1), 112.5 [C(CH3)2], 105–122 (m, 7 CF2,
CF3).
13C NMR (62 MHz, CDCl3) : δ = 20.6 (COCH3), 26.6, 27.1
[C(CH3)2], 66.0 (dd, JC-5,F = 20.9 Hz, JC-5,F’ = 30.3 Hz, C-5), 72.6
(CH2Ph), 76.1 (C-3), 82.6 (C-4), 82.7 (C-2), 104.8 (C-1), 112.5
[C(CH3)2], 105–120 (m, 7 CF2, CF3), 128.3, 128.4, 128.8, 137.0
(C6H5), 168.7 (COCH3).
19F NMR (235 MHz, acetone-d6): δ = –126.4 to –125.0 (m, 3 F, CF2),
–122.9 (s, 1 F, CF2), –122.1 to –121.9 (m, 9 F, CF2), –119.5 to –118.4
(m, 1 F, CF2CH2), –81.4 (CF3).
19F NMR (235 MHz, CDCl3): δ = –125.8 (s, 2 F, CF2CF3), –123.6 to
–119.9 (m, 11 F, CF2), –118.6 to –117.0 (m, 1 F, CF2CH2), –80.6 (CF3).
(5R)-5-C-Perfluorobutyl-D-xylose (7a): Compound 6a (0.36 g, 0.89
mmol) was deacetylated according to the general procedure D (reac-
tion time: 6 h). The residue was recrystallized from heptane/acetone
(Table 2).
(5S)-5-O-Acetyl-3-O-benzyl-1,2-O-isopropylidene-5-C-perfluorooc-
tyl-α-D-xylofuranose (5c): Compound 3c (0.40 g, 0.57 mmol) was
acetylated with Ac2O/pyridine as described in the general procedure
B. After column chromatographic separation (Rf = 0.69, eluent: hep-
tane/EtOAc, 5 : 1), the crystalline product 5c was isolated (Table 2).
1H NMR (250 MHz, CDCl3): δ = 1.31, 1.49 (s, 3 H, CH3), 1.95 (s, 3
H, COCH3), 3.98 (d, 1 H, J3,4 = 3.0 Hz, H-3), 4.46 (d, 1 H, J =
11.3 Hz, CH2Ph), 4.53 (dd, 1 H, J4,5 = 12.2 Hz, H-4), 4.54 (d, 1 H, J
= 11.3 Hz, CH2Ph), 4.54 (d, 1 H, J1,2 = 3.6 Hz, H-2), 5.87 (m, 1 H, H-
5), 5.94 (d, 1 H, J1,2 = 3.6 Hz, H-1), 7.26 –7.39 (m, 5 H, C6H5).
13C NMR (62 MHz, CDCl3) : δ = 20.1 (COCH3), 26.3, 26.8
[C(CH3)2], 66.7 (dd, JC-5,F = 23.7 Hz, JC-5,F’ = 27.3 Hz, C-5), 72.1
(CH2Ph), 75.9 (C-4), 80.5 (C-3), 81.6 (C-2), 105.8 (C-1), 112.3
[C(CH3)2], 105–120 (m, 7 CF2, CF3), 128.2, 128.6, 128.7, 136.6
(C6H5), 167.3 (COCH3).
19F NMR (235 MHz, CDCl3): δ = –127.1 to –118.0 (m, 3 CF2), –81.6
(CF3) (see also Table 3).
(5R)-5-C-Perfluorohexyl-D-xylose (7b): Compound 6b (1.14 g, 2.24
mmol) was deacetylated according to the general procedure D (reac-
tion time: 20 h). The residue was recrystallized from heptane/acetone
(Table 2).
19F NMR (235 MHz, CDCl3, CFCl3): δ = –126.6 to –118.0 (m, 5 CF2),
–81.4 (CF3) (see also Table 3).
(5R)-5-C-Perfluorooctyl-D-xylose (7c): Compound 6c (0.25 g,
0.4 mmol) was deacetylated according to the general procedure D (re-
action time: 20 h). The residue was recrystallized from heptane/ace-
tone (Table 2).
19F NMR (235 MHz, CDCl3): δ = –125.9 (s, 2 F, CF2CF3), –122.5 (s,
2 F, CF2), –121.4 (m, 10 F, CF2), –120.2 to –116.3 (m, 2 F, CF2CH2),
–80.6 (CF3).
19F NMR (235 MHz, CDCl3, CFCl3): δ = –126.7 to –116.6 (m, 7 CF2),
–81.4 (CF3) (see also Table 3).

SYNTHESIS
Papers
1038
(5R)-1,2,3,5-Tetra-O-acetyl-5-C-perfluorohexyl-β-D-xylofuranose
(8) and (5R)-1,2,3,4-Tetra-O-acetyl-5-C-perfluorohexyl-α-D-xylopy-
ranose (9): To an ice cooled solution of 7b (0.19 g, 0.4 mmol) in
Ac2O (0.7 mL) was added pyridine (0.7 mL) and the mixture was al-
lowed to warm up to r.t. and allowed to stand overnight. After addi-
tion of Et2O (10 mL) the organic phase was separated and washed
with satd aq citric acid solution (5 mL), satd aq NH4Cl solution (5
mL), and brine (5 mL). Then, the organic phase was dried (Na2SO4),
filtered and concentrated under reduced pressure. Traces of pyridine
could be removed by codistillation with CHCl3/toluene (7:3). The res-
idue was purified by column chromatography (eluent: heptane/
EtOAc, 5:1) yielding the syrupy β-furanose 8, and the syrupy α-pyr-
anose 9 (Table 2).
(b) Part 19: Zur, C.; Miethchen, R. Eur. J. Org. Chem. 1998,
531
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90/2.
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Soc. 1989, 111, 393.
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1974, 4, 35.
8:
1H NMR (250 MHz, acetone-d6): δ = 2.09, 2.10, 2.10, 2.12 (s, 3 H,
CH3), 4.76 (dd, J3,4 = 5.7 Hz, J4,5 = 8.3 Hz, 1 H, H-4), 5.17 (d, 1 H,
J2,3 = 1.6 Hz, H-2), 5.35 (ddd, 1 H, J3,5 = 2.8 Hz, H-3), 5.97–6.10 (m,
1 H, H-5), 6.03 (s, 1 H, H-1),
13C NMR (62 MHz, acetone-d6): δ = 20.2, 20.3, 20.6, 20.9 (CH3),
65.4 (dd, JC-5,F = 20.0 Hz, JC-5,F´ = 30.9 Hz, C-5), 74.1 (d, JC-3,F
=
2.7 Hz, C-3), 77.0 (C-4), 79.6 (C-2), 97.6 (C-1), 105–122 (m, 5 CF2,
CF3), 168.3, 169.0, 169.0, 169.2 (C=O).
(12) Lavaire, S.; Plantier-Royon, R.; Portella, C. Tetrahedron Asym-
metry 1998, 9, 213.
(13) Kitazume, T.; Ishikawa, N. J. Am.Chem. Soc. 1985, 107, 5186.
(14) Chen, Y.; Qi, M. J. Fluorine Chem. 1994, 66, 175.
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gical Effects, VCH: Weinheim, 1988.
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(22) Angyal, S. J.; Pickles, V. A. Aust. J. Chem. 1972, 25, 1695.
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(24) Grindley, T. B.; Gulasekharam, V. J. Chem. Soc., Chem. Com-
mun. 1978, 1073.
19F NMR (235 MHz, acetone-d6): δ = –125.9 (s, 2 F, CF2), –123.0 to
–121.3 (m, 7 F, CF2), –119.1 to –117.6 (m, 1 F, CF2CH2), –80.6 (s, 3
F, CF3).
9:
1H NMR (250 MHz, acetone-d6): δ = 2.06, 2.07, 2.08, 2.20 (s, 3 H,
CH3), 4.91 (ddd, 1 H, J3,4 = 7.5 Hz, J4,5 = 2.9 Hz, J4,F = 1.5 Hz, H-4),
5.32 (dd, 1 H, J1,2 = 4.5 Hz, J2,3 = 7.6 Hz, H-2), 5.54 (dd, 1 H, J2,3
=
7.6 Hz, J3,4 = 7.5 Hz, H-3), 5.51–5.61 (m, 1 H, H-5), 6.45 (d, 1 H, J1,2
= 4.5 Hz, H-1),
13C NMR (62 MHz, acetone-d6) : δ = 20.3, 20.4, 20.5, 20.8 (CH3),
65.1 (dd, JC-5,F = 21.2 Hz, JC-5,F’ = 26.8 Hz, C-5), 73.4 (C-3, C-4), 74.2
(C-2), 92.4 (C-1), 105–120 (m, 5 CF2, CF3), 168.2, 168.9, 169.6,
170.3 (C=O).
19F NMR (235 MHz, acetone-d6): δ = –126.1 to –116.3 (m, 10 F,
CF2), –80.6 (CF3).
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2, 211.
The authors are grateful to Dr. M. Michalik (Institut für Organische
Katalyseforschung e.V., University of Rostock) for recording the
NMR spectra. Furthermore, we thank the “Fonds der Chemischen
Industrie” for financial support and the HOECHST AG for a gift of
1-iodoperfluoroalkanes.
(28) Heathcock, C. H.; Ratcliffe, R. J. Am.Chem. Soc. 1971, 93,
1746.
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1986, 149, 464.
(1) (a) Presented at the 15th International Symposium on Fluorine
Chemistry in Vancouver, Canada, 2–7 August, 1997.