Concentrated hydriodic acid in simultaneous deprotections of multifunctional inositols

Article abstract of DOI:10.1016/j.carres.2004.11.031

L-1-Deoxy-1-fluoro-6-O-methyl-myo-inositol was epimerized by chloral/DCC in boiling 1,2-dichloroethane yielding d-1-O-cyclohexylcarbamoyl-2-deoxy-2-fluoro- 3-O-methyl-5,6-O-[(R/S)-2,2,2-trichloroethylidene]-chiro-inositol. The latter and l-4-O-benzyl-3-O-cyclohexylcarbamoyl-5-O-methyl-1,2-O-(2,2,2- trichloroethylidene)-muco-inositol, l-4-O-benzyl-3-O-cyclohexylcarbamoyl-1,2-O- ethylidene-5-O-methyl-muco-inositol, d-1-O-cyclohexylcarbamoyl-2-deoxy-5,6-O- ethylidene-2-fluoro-3-O-methyl-chiro-inositol, as well as d-5-O-benzyl-4-O- cyclohexylcarbamoyl-3-deoxy-3-(N,N′-dicyclohexylureido)-6-O-methyl-1, 2-O-(2,2,2-trichloroethylidene)-chiro-inositol were deprotected with boiling 57% aq hydrogen iodide. Ether, urethane and ethylidene acetal functions were simultaneously cleaved by the reagent, whereas the trichloroethylidene groups were still intact or were only removed in small quantities. Especially, the urea function of d-5-O-benzyl-4-O-cyclohexylcarbamoyl-3-deoxy-3-(N,N′- dicyclohexylureido)-6-O-methyl-1,2-O-(2,2,2-trichloroethylidene)-chiro-inositol was decomposed to a cyclohexylamino group. The hydrodechlorination of d-1-O-cyclohexylcarbamoyl-2-deoxy-2-fluoro-3-O-methyl-5,6-O-[(R/S)-2,2, 2-trichloroethylidene]-chiro-inositol using Raney-Nickel yielded a mixture of the corresponding 5,6-O-ethylidene- and 5,6-O-chloroethylidene derivatives. The three synthetic steps-hydrodehalogenation, HI-deprotection and peracylation- were combined without purification of the intermediates.

Full text of DOI:10.1016/j.carres.2004.11.031

Carbohydrate
RESEARCH
Carbohydrate Research 340 (2005) 741–748
Note
Concentrated hydriodic acid in simultaneous deprotections
of multifunctional inositolsI
a
a
b
Ralf Miethchen,a, Andreas Schmidt, Katharina Neitzel, Manfred Michalik,
*
Thomas Pundta and Wolfgang Rutha
aInstitut fu¨r Chemie, Universita¨t Rostock, Albert-Einstein-Strasse 3a, D-18059 Rostock, Germany
bInstitut fu¨r Organische Katalyseforschung an der Universita¨t Rostock, Buchbinderstrasse 5-6, D-18055 Rostock, Germany
Received 17 September 2004; received in revised form 15 November 2004; accepted 15 November 2004
Available online 25 January 2005
Abstract—L-1-Deoxy-1-fluoro-6-O-methyl-myo-inositol was epimerized by chloral/DCC in boiling 1,2-dichloroethane yielding D-1-
O-cyclohexylcarbamoyl-2-deoxy-2-fluoro-3-O-methyl-5,6-O-[(R/S)-2,2,2-trichloroethylidene]-chiro-inositol. The latter and L-4-O-
benzyl-3-O-cyclohexylcarbamoyl-5-O-methyl-1,2-O-(2,2,2-trichloroethylidene)-muco-inositol, L-4-O-benzyl-3-O-cyclohexylcarbamo-
yl-1,2-O-ethylidene-5-O-methyl-muco-inositol,
D-1-O-cyclohexylcarbamoyl-2-deoxy-5,6-O-ethylidene-2-fluoro-3-O-methyl-chiro-
inositol, as well as D-5-O-benzyl-4-O-cyclohexylcarbamoyl-3-deoxy-3-(N,N0-dicyclohexylureido)-6-O-methyl-1,2-O-(2,2,2-trichlo-
roethylidene)-chiro-inositol were deprotected with boiling 57% aq hydrogen iodide. Ether, urethane and ethylidene acetal functions
were simultaneously cleaved by the reagent, whereas the trichloroethylidene groups were still intact or were only removed in small
quantities. Especially, the urea function of D-5-O-benzyl-4-O-cyclohexylcarbamoyl-3-deoxy-3-(N,N0-dicyclohexylureido)-6-O-
methyl-1,2-O-(2,2,2-trichloroethylidene)-chiro-inositol was decomposed to a cyclohexylamino group. The hydrodechlorination of
D-1-O-cyclohexylcarbamoyl-2-deoxy-2-fluoro-3-O-methyl-5,6-O-[(R/S)-2,2,2-trichloroethylidene]-chiro-inositol using Raney-Nickel
yielded a mixture of the corresponding 5,6-O-ethylidene- and 5,6-O-chloroethylidene derivatives. The three synthetic steps—
hydrodehalogenation, HI-deprotection and peracylation- were combined without purification of the intermediates.
ꢀ 2005 Elsevier Ltd. All rights reserved.
Keywords: Inositols; Fluoroinositols; Epimerization; Deprotection; Hydrogen iodide
The separation of inositol derivatives from natural
sources is limited to a few representatives, so that vari-
ous compounds of this type have to be prepared by
chemical methods.2–5 A new access to rare inositol deriv-
atives from common diastereomers was opened by a
convenient one-pot procedure using the chloral/DCC re-
agent combination.1,6,7 This non-conventional acetaliza-
tion/epimerization reaction yields epimerized inositol
derivatives with useful protecting groups pattern (acetal,
carbamoyl, ureido and formyl).
Scheme 1 shows two examples starting with L-1-O-
benzyl-2-O-methyl-chiro-inositol (1)6 and L-1-deoxy-1-
fluoro-6-O-methyl-myo-inositol (4).1,8,
Recently, a review10 was published about the non-
conventional acetalizations/epimerizations of carbohy-
drates and inositols as well as about the possibilities
for a stepwise deprotection of these manifold functional-
ized products. Simultaneous deprotections of such epi-
merized cyclitols were not investigated so far. In this
paper, we report about the use of boiling 57% hydrogen
The numbering of the inositol derivatives based in this paper on the
numbering of the corresponding simple member of a group of
derivatives. Thus, D-2-deoxy-2-fluoro-chiro-inositol is the reference
substance for the consistent numbering of the derivatives 5 and 14–
18; D-3-amino-3-deoxy-chiro-inositol is reference for 3, 12 and 13 for
the nomenclature of inositols, see Ref. 9.
q Epimerization of carbohydrates and cyclitols, Part 20. For Part 19,
see Ref. 1.
*
Corresponding author. Tel.: +49 381 498 6420; fax: +49 381 498
6412; e-mail: ralf.miethchen@uni-rostock.de
0008-6215/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2004.11.031

742
R. Miethchen et al. / Carbohydrate Research 340 (2005) 741–748
O
Cl3C
O
Cy
OMe
N
H
OBn
OMe
O
CyHN
NHCy
O
OMe
HO
O
NHCy
OBn
HO
O
O
+
O
HO
OBn
OH
H
O
1
4
3
2
O
H
Cl3C
Cy
O
Cy
OMe
N
H
HN
O
O
CyHN
Cl3C
O
F
F
O
HO
HO
O
H
HO
OMe
OMe
NH-Cy
HO
O
OH
F
O
+
Cl3C
6
5
O
Cy = Cyclohexyl
Scheme 1. Non-classical epimerization of L-1-O-benzyl-2-O-methyl-chiro-inositol (1)6 and of L-1-deoxy-1-fluoro-6-O-methyl-myo-inositol (4)à with
chloral/DCC yielding the single inverted major products 2 and 5 as well as the double inverted minor products 3 and 6, respectively.
Cl3C
O
Cl3C
O
H
H
H
i
HO
H
OH
O
+
O
OMe
OH
O
O
OH
OH
2
NHCy
OBn
1
6
OH
OH
3
O
5
4
O
O
2 (endo-H form)
ii
O
H
H
7
8
iii
Cl3C
O
H3C
O
H
H
+
AcO
O
OAc
Ac
O
Ac
O
O
OMe
O
i
Ac
Ac
O
NHCy
OBn
O
OAc
O
OAc
O
Ac
10
9
Ac
O
11
8
O
H
iii
Bz
O
CyHN
H
O
CyHN
4
OBz
OBz
3
iv
i
OH
OH
3 (endo-H)
2
O
O
6
1
5
H
H
O
O
12
13
Cl3C
Cl3C
Scheme 2. One-pot deprotection of cyclitol derivatives 2, 3 and 11 by heating in 57% HI; (i) 57% HI, reflux, 2 h; (ii) Bu3SnH/AIBN;6 (iii) Ac2O,
pyridine, rt, 12 h; (iv) BzCl, pyridine, rt, 12 h; Cy = cyclohexyl.
iodide soln for simultaneous cleavages of several pro-
tecting groups. Concentrated hydriodic acid has been
already proved successful for the L-quebrachitol
demethylation.11
methyl-muco-inositol (11), prepared from 2 by hydrode-
chlorination with tributylstannane/AIBN,6 was com-
pletely deprotected to muco-inositol (8) by boiling
hydriodic acid. After acetylation of the latter and col-
umn chromatographic purification, the well-known
1,2,3,4,5,6-hexa-O-acetyl-muco-inositol (10) was ob-
tained.12–14
Compared with the examples above, the isolation of
aminoinositol 12, generated from the doubly inverted
epimerization product 3,6 by column chromatography
was difficult. Therefore, the crude product was first per-
benzoylated (peracetyl derivatives were not detectable by
TLC), and the UV active derivative 13 was then sepa-
rated by column chromatography (yield 45%). It is to
mention that a part of compound 13 was debenzoylated
in the course of the column chromatographic separation.
On refluxing of the inositol derivatives 2,6 36 and 116
in concentrated hydriodic acid for 2 h, the methoxy,
benzyloxy, carbamoyl and ethylidene groups were com-
pletely cleaved, whereas the trichloroethylidene group
was only removed in parts (Scheme 2). Elongation of
the reaction time from 2 to 16 h did not have apprecia-
ble influence on the product ratios. Thus, muco-inositol
derivative 2 yielded a 5:1 mixture of 1,2-O-trichloroethy-
lidene-muco-inositol (7) and muco-inositol (8). Because a
direct column chromatographic separation of minor
product 8 was difficult, the crude mixture of 7 and 8
was first peracetylated. The acetylated derivatives were
then isolated in yields of 74% (9) and 15% (10). L-4-O-
Benzyl-3-O-cyclohexylcarbamoyl-1,2-O-ethylidene-5-O-
à X-ray analysis reported in Ref. 1.

R. Miethchen et al. / Carbohydrate Research 340 (2005) 741–748
743
Fluorinated cyclitols are useful biological probes of
phosphatidylinositol metabolism. Recently, Schedler
and Baker15 gave a topical overview about the fluoro-
inositols synthesized so far; see also Ref. 16. As recently
reported in Ref. 1 and shown in Scheme 1, a further dia-
stereomeric fluorocyclitol derivative (compound 5) is
accessible by one-pot epimerization of L-1-deoxy-1-flu-
oro-6-O-methyl-myo-inositol (4). After the yield of com-
pounds 5 could be significantly increased from 18%1 to
61% (this paper) by use of a higher boiling solvent
(1,2-dichloroethane instead of dichloromethane), the
compound became important as precursor for further
D-2-deoxy-2-fluoro-chiro-inositol derivatives.
of 5, because also fluoro-free products were formed, a
consequence of competing hydrodefluorinations.18,19
By contrast, Raney-Nickel did not cause hydrodefluori-
nation, but it resulted from 5 a mixture of ethylidene
acetal 14 and monochloroethylidene acetal 15 (ratio
1.3:1; estimated by NMR); for hydrodechlorinations of
chloralacetals in the carbohydrate chemistry see also
Ref. 20.
The chromatographic properties of compounds 14
and 15 are very similar. The first fraction, obtained by
recrystallization of the 14/15 mixture from cyclohex-
ane/2-propanol (10:1) contained exclusively the endo-H
diastereomers of 14 and 15. This fraction allowed a
NMR spectroscopic analysis of the two compounds.
For the HI-deprotection of 14/15, the whole mixture
was used. It was even possible to combine the hydrode-
chlorination, HI-deprotection and peracetylation proce-
dures without column chromatographic purification of
the intermediates. In this way, D-1,3,4,5,6-penta-O-ace-
tyl-2-deoxy-2-fluoro-chiro-inositol (16) was obtained in
40% yield related to starting material 5 (Scheme 3).
The synthesis of the parent compound D-2-deoxy-2-
fluoro-chiro-inositol from the mixture of 14 and 15
was reported in a preliminary communication.21
The structures of the new compounds are supported
by their NMR spectra; assignments of the signals based
on two-dimensional 1H,1H- and 13C,1H-correlations
spectra. Key signals attributable with confidence to a
definite position were found out from typical correla-
tions in the case of the fluorocyclitols (coupling of the
ring protons and ring carbons with fluorine). On this ba-
sis the assignment of signals for the other ring atoms be-
came possible. The atomic configurations of adjacent
ring protons were assigned with the assistance of the
Karplus relationship.22 The spectra of 5, 7, 9, 12, 13,
17, 18 (endo-H form) and 18 (exo-H form) show the
Compound 5 is a mixture of diastereomers, because
the chiral C-atom of the acetal moiety is either (S)- or
(R)-configurated. The endo-H diastereomer, D-5,6-O-
[(S)-2,2,2-trichloroethylidene]-1-O-cyclohexylcarbamoyl-
2-deoxy-2-fluoro-3-O-methyl-chiro-inositol, predominates
in this mixture [(endo-H):(exo-H) ꢀ 7.1:1]. Selected
reactions of this diastereomeric mixture are shown in
Scheme 3. Thus, it was treated with boiling concentrated
hydriodic acid for 2 h. D-5,6-O-[(S)-2,2,2-Trichloroethyl-
idene]-2-deoxy-2-fluoro-chiro-inositol (17) was formed
and isolated (yield 64%). In a second experiment, the
crude product obtained after the HI-deprotection of 5
was acetylated. Also in this case, only products were
found with an intact trichloroethylidene group, that
is, D-1,3,4-tri-O-acetyl-5,6-O-[(S)-2,2,2-trichloroethylid-
ene]-2-deoxy-2-fluoro-chiro-inositol (18) in a yield of
76% and its exo-H diastereomer in a yield of 11%. This
result shows that the trichloroethylidene group has to be
first converted into an acid-unstable ethylidene group
before a simultaneous total deprotection of the inositol
derivative with hydriodic acid is possible.
Tributylstannane/AIBN6,10,17 proved to be an
unsuited reagent for the desired hydrodechlorination
H
H
O
O
R
Cl3C
2
1
6
F
F
F
4
O
O
HO
HO
5
3
OMe
OMe
NH-Cy
OMe
NH-Cy
i
ii
HO
O
HO
O
HO
OH
H
O
4
O
5
14 (R=CH3)
+ 15 (R=CH2Cl)
iii
ii, iii, iv
O
Ac
O
Cl3C
F
F
OH
AcO
O
OAc
iv
AcO
O
Ac
HO
O
H
17
16
Cl
H
3C
H
O
O
Cl3C
+
F
OAc
F
O
O
OAc
AcO
O
Ac
AcO
O
Ac
18 (endo-H form)
18 (exo-H-form)
Scheme 3. (i) = Chloral/DCC, (CH2Cl)2, reflux, 8 h; (ii) = Raney-Nickel/H2, EtOH; (iii) = 57% HI, reflux, 2 h; (iv) = Ac2O, pyridine, rt, 12 h.

744
R. Miethchen et al. / Carbohydrate Research 340 (2005) 741–748
characteristic signals of a trichloroethylidene group. The
latter is characterized by the singlet of the acetal proton
(d ꢀ 5.28–5.93) and by the C signals of the acetal moiety
1. Experimental
1.1. General
(dCH ꢀ 105.4–112.6; dCCl ꢀ 96.0–105.6).
3
The cyclic chloral acetals generated by a non-conven-
tional epimerization reaction with chloral/DCC are mix-
tures of endo-H and exo-H diastereomers. The singlet
of the acetal proton is a good marker to distinguish
between the two diastereomeric forms, because the
endo-H proton is always about 0.1–0.25 ppm downfield
shifted compared to the corresponding exo-H signal.10
In the case of the compound 5 the ratio of endo-H form
to exo-H form, estimated by integration of the two ace-
tal-H singlets, was about 7:1 (d endo-H = 5.39, d exo-
H = 5.28). The corresponding singlets of 18 (endo-H
form) and 18 (exo-H form) were found at d 5.49 and d
5.35, respectively.
Melting points were measured using a polarizing micro-
scope Leitz (Laborlux 12 Pol) equipped with a hot stage
(Mettler FP 90). H NMR and 13C NMR spectra were
1
recorded on Bruker spectrometers AC 250 (250.13 and
62.9 MHz, respectively), and AVANCE 500 (500.13
and 125.8 MHz, respectively). Calibration of spectra
was carried out by means of solvent peaks. (CDCl3: d
1H = 7.25, d 13C = 77.0; CD3OD:
d
1H = 3.30,
d
13C = 49.0; (CD3)2CO:
d d
1H = 2.04, 13C = 29.8;
Me2SO-d6: d H = 2.5, d 13C = 39.7). 19F NMR spectra
were recorded at 235.2 MHz (spectrometer AC 250, d
19F values referenced to CFCl3). Optical rotations were
measured on a Polar LlP (IBZ Meßtechnik). LC–MS:
LCQ Advantage, ESI-mode (Thermo Finnigan). Col-
umn chromatography: Particle size for silica gel 63–
200 lm; thin layer chromatography (TLC): E. Merck
Silica Gel 60 F254 foils; Chemicals: 57% aq HI (Riedel
de Hae¨n), zinc dust (E. Merck).
1
The ethylidene groups of compounds 116 and 14 (endo-
H form) are characterized by a doublet for the methyl
group at about 5.29–5.30 ppm and by a doublet of the
methyl group at about 1.30–1.36 ppm. The correspond-
ing signals of the chloroethylidene group of compound
15 (endo-H form) were found at 5.38 ppm (triplet); see
also Ref. 6. In the case of the mixture from 14 and 15,
all signals of the two endo-H diastereomers could be ex-
actly assigned. The crude mixture of 14 and 15 shows in
the 19F NMR spectrum as expected four singlets for the
two endo-H (d À199.9 and À202.4) and the two exo-H
isomers (d À198.1 and À199.2).
1.2. D-1-O-Cyclohexylcarbamoyl-2-deoxy-2-fluoro-3-O-
methyl-5,6-O-[(S)-2,2,2-trichloroethylidene]-chiro-inositol
(5 endo-H) and D-1-O-cyclohexylcarbamoyl-2-deoxy-2-
fluoro-3-O-methyl-5,6-O-[(R)-2,2,2-trichloroethylidene]-
chiro-inositol (5 exo-H) by epimerization
Whereas the chair conformation of aminoinositol 12
(Scheme 2) corresponds to the coupling constants of
the compound, the benzoyl derivative 13 shows strong
divergences in this point. The coupling constants of
the ring protons indicate a boat or twisted boat confor-
mation of 13.
To a suspension of L-1-deoxy-1-fluoro-6-O-methyl-myo-
inositol (4)1 (1.0 g, 5.1 mmol) in (CH2Cl)2 (40 mL),
DCC (3.16 g, 15.3 mmol) and chloral (1.7 mL,
17.8 mmol) were subsequently added with stirring at rt
(argon atmosphere). Then the mixture was refluxed for
8 h. The work up procedure is analogous to that de-
scribed in Ref. 1. The crystalline mixture of 5 (1.4 g,
61%, 5 (endo-H):5 (exo-H) ꢀ 7.1:1) and 6 (0.27 g, 8%)
were separated by column chromatography (3:1 hep-
tane/EtOAc). The pure diastereomer 5 (endo-H) could
be obtained by fractionated crystallization from cyclo-
hexane (mp 145–146 ꢁC); Ref. 1 mp 145–146 ꢁC. LC–
MS [(M+H): m/z 452.0.
In conclusion, the simultaneous complete deprotec-
tion of non-classically epimerized inositols with a very
different pattern of protecting groups was solved using
boiling 57% HI. With that in hand, a rapid access was
achieved to well-known (but rare) inositols and to new
epimeric inositols (e.g., fluoroinositol diastereomers).
Refluxing of the inositols 2 (endo-H form), 3 (endo-H
form), 5 and 11 in 57% hydrogen iodide resulted in
simultaneous cleavage of the ether, urethane and ethyl-
idene acetal protecting groups within 2 h. Additionally,
a small percentage of the cyclic chloral acetal function
was removed under this reaction conditions in the case
of compound 2. Prolongation of the reaction time from
2 to 16 h did not have an appreciable influence on the
result. To achieve the simultaneous cleavage of all pro-
tecting groups by 57% hydrogen iodide, a preceding
hydrodechlorination of the trichloroethylidene group
of 2 and 5 was required.
1
Compound 5 (endo-H): H NMR (500 MHz, CDCl3):
d 5.39 (s, 1H, CHCCl3), 5.17 (ddd, 1H, J1,F ꢀ 21.8,
J1,2 ꢀ 2.8, J1,6 ꢀ 6.0 Hz, H-1), 4.76 (ddd, 1H,
J2,F ꢀ 48.2, J1,2 ꢀ 2.8, J2,3 ꢀ 5.0 Hz, H-2), 4.68 (m,
2H, H-6, NH), 4.56 (ddd, 1H, J5,F ꢀ 1.3, J4,5 ꢀ 8.5,
J5,6 ꢀ 6.6 Hz, H-5), 3.67 (ÔtÕ, 1H, J3,4 ꢀ 8.5 Hz, H-4),
3.48 (s, 3H, OCH3), 3.40 (ddd, 1H, J3,F ꢀ 15.7,
J2,3 ꢀ 5.0, J3,4 ꢀ 8.5 Hz, H-3) 3.40 (m, 1H, cyclohexyl–
CH) 2.78 (br, 1H, OH), 1.88 (m, 2H, cyclohexyl–CH2),
1.64 (m, 2H, cyclohexyl–CH2), 1.53 (m, 1H, cyclo-
hexyl–CH2) 1.27 (m, 2H, cyclohexyl–CH2), 1.09 (m,
3H, cyclohexyl–CH2); 13C{1H} NMR (125.8 MHz,
CDCl3): d 153.8 (C(O)NH), 107.3 (CHCCl3), 99.3
N,N0-Dicyclohexylureido groups are decomposed by
hydrogen iodide to cyclohexylamino groups as already
observed in the reaction of 3 with acetic acid.6

R. Miethchen et al. / Carbohydrate Research 340 (2005) 741–748
745
(CCl3), 90.6 (d, JC,F ꢀ 199.0 Hz, C-2), 81.0 (d,
1.4. Deprotection of epimerized inositol derivatives by
hydrogen iodide soln followed by acylation of the crude
products—general procedure
JC,F ꢀ 23.0 Hz, C-3), 80.5 (C-5), 76.7 (d, JC,F ꢀ 7.0 Hz,
C-6), 72.0 (d, JC,F ꢀ 7.0 Hz, C-4), 69.8 (d,
JC,F ꢀ 18.0 Hz, C-1), 59.4 (OCH3), 50.3 (cyclohexyl–
CH), 33.2 (2·), 25.4, 24.7 (2·) (5C, cyclohexyl–CH2);
19F{1H} NMR (235 MHz, CDCl3): d À202.7 (s).
Compound 5 (exo-H): acetal proton d 5.28 (s).
A soln of the corresponding inositol (1.0 mmol) in 57%
aq HI-soln (2 mL) was refluxed for 2 h (Ar) and then
concentrated under diminished pressure. Then the crude
residue was peracylated with Ac2O (2 mL) and pyridine
(5 mL) or with benzoylchloride/pyridine (only com-
pound 3, endo-H) for 12 h at rt. After concentration
of the acylation mixture under diminished pressure,
the corresponding crude product was three times co-dis-
tilled with 5 mL of toluene followed by column chro-
matographic separation.
1.3. Deprotection of epimerized inositol derivatives by
hydrogen iodide soln§—general procedure
A soln of the corresponding inositol (1.0 mmol) in 57%
aq HI-soln (2 mL) was refluxed for 2 h (Ar) and then
concentrated under diminished pressure. The crude res-
idue was purified by column chromatography.
1.4.1. 3,4,5,6-Tetra-O-acetyl-1,2-O-(2,2,2-trichloroethy-
lidene)-muco-inositol (9) and 1,2,3,4,5,6-hexa-O-acetyl-
muco-inositol (10). The L-4-O-benzyl-1,2-O-(2,2,2-tri-
chloroethylidene)-3-O-cyclohexylcarbamoyl-5-O-methyl-
muco-inositol (2, endo-H diastereomer)6 (500 mg,
0.93 mmol) was successively deprotected to 7/8 and acet-
ylated as described in the general procedure yielding the
crude mixture of 9/10. After column chromatographic
separation (gradient: heptane/EtOAc 1:2 ! heptane/
EtOAc) 65 mg (16%) of 10; colourless crystals (6:1
cyclohexane/EtOAc), mp 182–183 ꢁC, Rf 0.26 (1:1 hep-
tane/EtOAc) and 329 mg (74%) of 9; colourless crystals
(cyclohexane), mp 141–143 ꢁC, Rf 0.29 (1:1 heptane/
EtOAc) were isolated.
1.3.1.
1,2-O-(2,2,2-Trichloroethylidene)-muco-inositol
(7). The muco-inositol derivative 2 (endo-H)6 (440 mg,
0.82 mmol) yielded after chromatographic purification
(EtOAc) 152 mg (60%) of 7, colourless crystals (diethyl
ether), mp 111–113 ꢁC; Rf 0.37 (5:1 CHCl3–MeOH);
1H NMR (250 MHz, CD3OD): d 5.87 (s, 1H, CHCCl3),
4.88 (m, 2H, J1,2 ꢀ 4.1 Hz, H-1, H-2), 4.28 (m, 2H, H-3,
H-6), 4.09 (dd, 2H, J3,4 ꢀ 8.9, J4,5 ꢀ 2.9 Hz, H-4, H-5);
13C NMR (125.8 MHz, CD3OD): d 108.4 (CHCCl3),
100.8 (CCl3), 83.4 (C-1, C-2), 73.3 (C-3, C-6), 71.9 (C-
4, C-5). Anal. Calcd for C8H11Cl3O6 (309.53): C,
31.04; H, 3.58. Found: C, 30.89; H, 3.40.
1
Compound 9: H NMR (500 MHz, CDCl3): d 5.51 (s,
1H, CHCCl3), 5.50 (m, 2H, H-3, H-6), 5.23 (m, 2H, H-4,
H-5), 4.62 (m, 2H, H-1, H-2), 2.12 (s, 6H, acetyl–CH3),
2.08 (s, 6H, 2 · CH3); 13C NMR (62.9 MHz, CDCl3): d
169.6, 169.1 (2 · C@O), 106.1 (CHCCl3), 98.5 (CCl3),
78.4 (C-1, C-2), 68.1 (C-4, C-5), 67.2 (C-3, C-6), 20.7,
20.7 (2 · CH3). Anal. Calcd for C16H19Cl3O10 (477.68):
C, 40.23; H, 4.01. Found: C, 40.49; H, 4.06.
1.3.2. D-2-Deoxy-2-fluoro-5,6-O-[(S)-2,2,2-trichloroethy-
(17). D-5,6-O-[(R/S)-2,2,2-Tri-
chloroethylidene]-1-O-cyclohexylcarbamoyl-2-deoxy-2-
fluoro-3-O-methyl-chiro-inositol (5)1 (740 mg, 1.65
mmol) yielded after chromatographic separation (30:1
CHCl3–MeOH), 330 mg (64%) of 17, colourless crystals
lidene]-chiro-inositol
(diethyl ether), mp 156–157 ꢁC, Rf 0.32 (5:1 CHCl3–
1
22
Compound 10: H NMR (500 MHz, Me2SO-d6 ): d
MeOH), ½aŠ þ 66:2 (c 0.66, MeOH), were isolated; 17
D
1
5.30–5.26 (br m, 2H, H-3, H-6), 5.19–5.16 (m, 4H, H-
1, H-2, H-4, H-5), 2.08 (s, 6H, 2 · CH3), 2.04 (s, 12H,
4 · CH3); 13C NMR (125.8 MHz, Me2SO-d6): d 169.5
(C@O), 169.1 (C@O), 68.3 (C1, C2, C4, C5), 66.9 (C3,
C6), 20.5 (CH3). Anal. Calcd for C18H24O12 (432.38):
C, 50.00; H, 5.60. Found: C, 50.19; H, 5,56.
(endo-H form): H NMR (250 MHz, CD3OD): d 5.52
(s, 1H, CHCCl3), 4.61 (ddd, 1H, J1,6 ꢀ 4.1,
J5,6 ꢀ 5.7 Hz, H-6), 4.50 (dd, 1H, J4,5 ꢀ 8.0 Hz, H-5),
4.44 (ddd, 1H, J2,F ꢀ 48.0, J1,2 ꢀ 3.0, J2,3 ꢀ 7.7 Hz, H-
2), 4.31 (ddd, 1H, J1,F ꢀ 14.2 Hz, H-1), 3.86 (ddd, 1H,
J3,F ꢀ 16.9, J3,4 ꢀ 9.2 Hz, H-3), 3.54 (t, 1H, H-4); 13C
NMR (125.8 MHz, CD3OD): d 112.6 (CHCCl3), 105.6
(CCl3), 98.5 (d, JC,F ꢀ 180.0 Hz, C-2), 88.1 (C-5), 85.3
(d, JC,F ꢀ 8.0 Hz, C-6), 79.1 (d, JC,F ꢀ 8.0 Hz, C-4),
76.2 (d, JC,F ꢀ 20.0 Hz, C-3), 73.4 (d, JC,F ꢀ 18.0 Hz,
C-1); 19F{1H} NMR (235 MHz, CDCl3): d À202.8 (s).
Anal. Calcd for C8H10Cl3FO5 (311.52): C, 30.84; H,
3.24. Found: C, 30.99; H, 3.26.
1.4.2. 1,2,3,4,5,6,-Hexa-O-acetyl-muco-inositol (10).
A
soln of the muco-inositol derivative 116 (360 mg,
0.83 mmol) in 57% aq HI (2 mL) was refluxed for 2 h
(Ar). After concentration of the mixture under dimin-
ished pressure, the residue was treated with Ac2O
(5 mL) and pyridine (2 mL) for 12 h at rt. Then, the mix-
ture was poured on ice. After stirring for 30 min, com-
pound 10 was extracted with ether. The crude product
obtained by concentration of the combined ether phases
was several times co-distilled with toluene before col-
umn chromatographic purification (Rf 0.25, 4:1
§
Procedure corresponding to Angyal and Hoskinson;11 HI was first
distilled over zinc dust.

746
R. Miethchen et al. / Carbohydrate Research 340 (2005) 741–748
heptane/EtOAc). Yield: 165 mg (46%) of 10; colourless
crystals (6:1 cyclohexane/EtOAc), mp 182–183 ꢁC
(lit.14 179–180 ꢁC) NMR data analogous to those de-
scribed in paragraph 1.4.1.
129.2, 129.2, 129.1, 128.9, 128.9, 128.7 (Ph–C); 105.4
(CHCCl3), 99.2 (CCl3), 82.3 (C-4), 76.3 (C-5); 71.6,
70.7 (C-1, C-2); 68.1 (C-6), 55.9 (C-3), 54.9 (cyclo-
hexyl–CH); 33.7, 33.4 (2,20-cyclohexyl–CH2); 25.8 (4-
cyclohexyl–CH2); 24.4, 24.4 (3,30-cyclohexyl–CH2). IR
(Nujol): NH band 3425.5 cmÀ1. LC–MS m/z 703.1.
Anal. Calcd for C35H34Cl3NO8 (703.02): C, 59.80; H,
4.88; N, 2.00. Found C, 60.20; H, 4.92; N, 1.85.
1.4.3. D-4,5,6-Tri-O-benzoyl-3-cyclohexylamino-3-deoxy-
1,2-O-(2,2,2-trichloroethylidene)-chiro-inositol (13). D-
5-O-Benzyl-4-O-cyclohexylcarbamoyl-3-deoxy-3-(N,N0-
dicyclohexylureido)-6-O-methyl-1,2-O-trichloroethylid-
ene-chiro-inositol (3 endo-H)6 (400 mg, 0.54 mmol) was
deprotected to D-1,2-O-(2,2,2-trichloroethylidene)-3-
cyclohexylamino-3-deoxy-chiro-inositol (12)– as de-
scribed in the general procedures 1.3. The crude product
13 was dissolved in CH2Cl2–pyridine (7 mL, 1:1) and
then benzoyl chloride (0.31 mL, 2.7 mmol) was added
with cooling. After the mixture was allowed to react
for 12 h at rt, the colourless precipitate was removed
by filtration and washed with CH2Cl2 (15 mL). The
combined filtrates were subsequently washed with water
(10 mL), satd aq NaHCO3 soln (10 mL) and 5%-NaH-
SO4 soln (10 mL), dried (Na2SO4) and concentrated
under diminished pressure. Compound 13 (167 mg, 44%)
was separated by column chromatography (15:1!1:1
1.4.4. D-1-O-Cyclohexylcarbamoyl-2-deoxy-5,6-O-ethyli-
dene-2-fluoro-3-O-methyl-chiro-inositol (14) and D-5,6-O-
(2-chloroethylidene)-1-O-cyclohexylcarbamoyl-2-deoxy-
2-fluoro-3-O-methyl-chiro-inositol (15). To a stirred
soln of 5 (650 mg, 1.44 mmol) in EtOH (10 mL)
Raney-Ni (1.0 g) was added (H2-atmosphere). After
the suspension was stirred for 8 h at rt, triethylamine
(1 mL) was added and stirring was continued for 8 h.
Then the mixture was filtered through Kieselguhr, and
the filtrate was concentrated under diminished pressure.
After column chromatographic purification (1:1 hep-
tane/EtOAc), 445 mg of a crystalline mixture of the eth-
ylidene acetals 14 and the chloroethylidene acetal (15)
were isolated (14:15 ꢀ 1.3:1); Rf 0.20 (1:3 heptane/
EtOAc). Recrystallization of this four component frac-
tion from 10:1 cyclohexane/i-PrOH gave a mixture of
the endo-H isomers of 14 and 15, colourless fine needles,
which were ÔfeltedÕ. One of the compounds melts at 152–
154 ꢁC, the other at 161–163 ꢁC (polarizing microscope).
The two exo-H isomers of 14 and 15, enriched in the fil-
trate, were detected by LC–MS [(M+H): m/z 348 and
382, respectively]. Their 19F NMR singlets were found
at d À198.1 and À199.2.
heptane/EtOAc). Colourless needles (i-PrOH), mp
23
D
161–162 ꢁC, Rf 0.28 (1:1 heptane/EtOAc), ½aŠ +118.3
(c 0.50, CHCl3).
Compound 12: H NMR (500 MHz, CD3OD): d 5.58
1
(s, 1H, CHCCl3), 4.69 (dd, 1H, J1,2 ꢀ 5.5, J2,3
ꢀ
8.2 Hz, H-2), 4.62 (dd, 1H, J1,2 ꢀ 5.5, J1,6 ꢀ 3.5 Hz, H-
1), 4.18 (ÔtÕ, 1H, J1,6 ꢀ 3.5, J5,6 ꢀ 3.1 Hz, H-6), 3.71
(dd, 1H, J3,4 ꢀ 9.5, J4,5 ꢀ 8.7 Hz, H-4), 3.65 (dd, 1H,
J4,5 ꢀ 8.7, J5,6 ꢀ 3.1 Hz, H-5), 3.13 (dd, 1H, J2,3 ꢀ 8.2,
J3,4 ꢀ 9.5 Hz, H-3), 3.10 (m, 1H, CH), 2.20–1.10 (m,
10H, cyclohexyl–CH2); 13C NMR (125.8 MHz,
CD3OD): d 107.7 (CHCCl3), 100.7 (CCl3), 81.7 (C-2),
81.3 (C-1), 73.1 (C-5), 70.3 (C-4), 70.0 (C-6), 59.3 (C-
3), 56.7 (cyclohexyl–CH), 33.6, 32.4, 26.8, 26.2, 26.0
(cyclohexyl–CH2). LC–MS: m/z 390.1.
Compound 14 (endo-H): 1H NMR (500 MHz, CDCl3):
d 5.29 (q, 1H, J ꢀ 5.0 Hz, CHCH3), 5.29 (m, 1H, H-1),
4.80 (ddd, 1H, J2,F ꢀ 48.2, J1,2 ꢀ 3.0, J2,3 ꢀ 6.0 Hz, H-
2), 4.72 (d, 1H, J ꢀ 8.0 Hz, NH), 4.40–4.26 (m, H-5,
H-6), 3.69 (ÔtÕ, 1H, J3,4 ꢀ J4,5 ꢀ 8.5 Hz, H-4), 3.56 (s,
3H, OCH3), 3.55–3.40 (m, 2H, H-3, cyclohexyl–CH),
2.68 (br, 1H, OH), 1.96–1.11 (m, 10H, cyclohexyl–
CH2), 1.36 (d, 1H, J ꢀ 5.0 Hz, CH3CH); 13C{1H}
NMR (125.8 MHz, CDCl3): d 154.1 (C(O)NH), 100.8
(CHCH3), 90.9 (d, JC,F ꢀ 182.2 Hz, C-2), 81.6 (d,
JC,F ꢀ 23.8 Hz, C-3), 78.2 (C-5), 75.1 (d, JC,F ꢀ 6.5 Hz,
C-6), 71.4 (d, JC,F ꢀ 7.5 Hz, C-4), 69.5 (d, JC,F 17.5 Hz,
C-1), 59.6 (OCH3), 50.3 (cyclohexyl–CH), 33.2 (2·),
25.4, 24.7 (2·) (cyclohexyl–CH2), 20.1 (CHCH3);
19F{1H} NMR (235 MHz, CDCl3): d À199.9 (s). LC–
MS (M+H): m/z 348.
Compound 15 (endo-H): 1H NMR (500 MHz, CDCl3):
d 5.38 (t, 1H, J ꢀ 4.0 Hz, ClCH2CH), 5.18 (ddd, 1H,
JF,H ꢀ 22.5, J1,2 ꢀ 3.0, J1,6 ꢀ 6.3 Hz, H-1), 4.81 (ddd,
1H, J2,F ꢀ 48.5, J1,2 ꢀ 3.0, J2,3 ꢀ 5.0 Hz, H-2), 4.72 (d,
1H, J ꢀ 8.0 Hz, NH), 4.40–4.26 (m, 2H, H-5, H-6),
3.73 (ÔtÕ, 1H, J3,4 ꢀ J4,5 ꢀ 8.5 Hz, H-4), 3.54 (s, 3H,
OCH3), 3.55–3.40 (m, 4H, H-3, cyclohexyl–CH,
CHCH2Cl), 2.68 (br, 1H, OH), 1.96–1.11 (m, 10H,
Compound 13: 1H NMR (500 MHz, Me2SO-d6): d 8.02
(m, 2H, o-Ph), 7.92 (m, 2H, o-Ph), 7.75–7.69 (m, 3H, o-
Ph, p-Ph), 7.63–7.51 (m, 4H, 2 · p-Ph, m-Ph), 7.48 (m,
2H, m-Ph), 7.37 (m, 2H, m-Ph), 5.93 (s, 1H, CHCCl3),
5.93 (m, 1H, H-6), 5.66–5.60 (m, 2H, H-1, H-2), 4.96
(dd, 1H, J3,4 ꢀ 6.5, J4,5 ꢀ 5.5 Hz, H-4), 4.76 (dd, 1H,
J5,6 ꢀ 4.0 Hz, H-5), 3.50 (br m, 1H, H-3), 2.72 (br m,
1H, cyclohexyl–CH), 1.93–0.81 (m, 10H, cyclohexyl–
CH2); 13C NMR (125.8 MHz, Me2SO-d6): d 165.5
(COC6H5), 164.9 (COC6H5), 164.7 (COC6H5), 134.2 (i-
Ph), 133.9 (i-Ph), 133.6 (i-Ph); 129.7, 129.5, 129.4,
– After neutralization of the crude product mixture with methanolic
Et3N, a column chromatographic separation of compound 12 was
attempted. However, 12 could only be accumulated but not be
isolated in pure form. The contaminated solid of 12 obtained was
investigated by LC–MS. Besides the major product 12 (molar mass
390) a second product (molar mass 497), which likewise contains a
2,2,2-trichloroethylidene group, was detected.

R. Miethchen et al. / Carbohydrate Research 340 (2005) 741–748
747
cyclohexyl–CH2); 13C{1H} NMR (125.8 MHz, CDCl3):
153.9 (C(O)NH), 102.1 (CHCH2Cl), 90.8 (d,
1H, J3,F ꢀ 12.5, J2,3 ꢀ 6.3, J3,4 ꢀ 8.5 Hz, H-3), 5.22
(m, 1H, H-4), 4.81 (ddd, 1H, J2,F ꢀ 47.0, J1,2 ꢀ 2.8,
J2,3 ꢀ 6.3 Hz, H-2), 4.75–4.72 (m, 2H, H-5, H-6), 2.17,
2.12, 2.09 (3s, 9H, 3 · CH3); 13C NMR (62.9 MHz,
d
JC,F ꢀ 183.4 Hz, C-2), 81.0 (d, JC,F ꢀ 21.2 Hz, C-3),
79.0 (C-5), 74.0 (d, JC,F ꢀ 6.5 Hz, C-6), 70.7 (d,
JC,F ꢀ 7.5 Hz, C-4), 69.5 (d, JC,F ꢀ 17.5 Hz, C-1),
59.2 (OCH3), 50.2 (cyclohexyl–CH), 44.6 (CH2Cl),
33.2 (2·), 25.4, 24.7 (2·) (5C, cyclohexyl–CH2);
19F{1H} NMR (235 MHz, CDCl3): d À202.4 (s). LC–
MS (M+H): m/z 382.
CDCl3):
d 169.8, 169.6, 169.3 (3 · C@O), 106.9
(CHCCl3), 98.6 (CCl3), 88.5 (d, JC,F ꢀ 186.0 Hz, C-2),
78.5 (s, C-5), 76.5 (d, JC,F ꢀ 7.2 Hz, C-6), 70.3 (d,
JC,F ꢀ 5.5 Hz, C-4), 69.9 (d, JC,F ꢀ 25.5 Hz, C-3), 68.5
(d, JC,F ꢀ 17.5 Hz, C-1), 20.7, 20.7, 20.6 (3 · CH3);
19F{1H} NMR (235 MHz, CDCl3): d À203.5. Anal.
Calcd for C14H16Cl3FO8 (437.63): C, 38.42; H, 3.69.
Found: C, 38.77; H, 3.53.
1.4.5. D-1,3,4,5,6-Penta-O-acetyl-2-deoxy-2-fluoro-chiro-
inositol (16). To
a stirred soln of 5 (3.40 mg,
0.75 mmol) in EtOH (5 mL) Raney-Ni (0.5 g) was added
(H2-atmosphere). After the suspension was stirred for
8 h at rt, triethylamine (1 mL) was added and stirring
was continued for 8 h. Then the mixture was filtered
through Kieselguhr, and the filtrate was concentrated
under diminished pressure. The residue (316 mg) was re-
fluxed for 2 h in 57% aq HI-soln (2 mL). The soln was
then concentrated under diminished pressure followed
by acetylation of the residue and isolation of compound
16 as described for compound 10 (Rf 0.18, 1:1 heptane/
Compound 18 (exo-H form): 1H NMR (500 MHz,
CDCl3): d 5.61 (ddd, 1H, J1,F ꢀ 21.8, J1,2 ꢀ 2.5,
J1,6 ꢀ 5.0 Hz, H-1), 5.55 (ÔqÕ, 1H, J4,F ꢀ J4,5 ꢀ 7.5,
J3,4 ꢀ 8.0 Hz, H-4), 5.35 (s, 1H, CHCCl3), 5.31 (ddd,
1H, J3,F ꢀ 12.5, J2,3 ꢀ 5.5, J3,4 ꢀ 8.0 Hz, H-3), 4.90
(ddd, 1H, J2,F ꢀ 47.2, J1,2 ꢀ 2.5, J2,3 ꢀ 5.5 Hz, H-2),
4.64–4.58 (m, 2H, H-5, H-6), 2.20, 2.11, 2.10 (3s, 9H,
3 · CH3); 13C NMR (62.9 MHz, CDCl3): d 169.7,
169.5, 169.2 (3 · C@O), 107.2 (CHCCl3), 96.0 (CCl3),
88.9 (d, JC,F ꢀ 185.2 Hz, C-2), 76.9 (s, C-5), 76.88 (d,
JC,F ꢀ 7.3 Hz, C-6), 72.5 (d, JC,F ꢀ 4.6 Hz, C-4), 70.8
(d, JC,F ꢀ 26.8 Hz, C-3), 69.3 (d, JC,F ꢀ 18.2 Hz, C-1),
20.70, 20.65, 20.58 (3s, 3 · CH3); 19F{1H} NMR
(235 MHz, CDCl3): d À201.7.
EtOAc). Yield of 16: 117 mg (40% related to 5); colour-
22
less syrup, ½aŠ +27.0 (c 0.86, CHCl3).
D
1H NMR (500 MHz, CDCl3): d 5.52–5.46 (m, 2H, H-
3, H-1), 5.41 (ÔqÕ, J6,F ꢀ J1,6 ꢀ J5,6 ꢀ 3.5 Hz, 1H, H-6),
5.36 (ÔtÕ, 1H, J4,F ꢀ J3,4 ꢀ J4,5 ꢀ 10.2 Hz, H-4), 5.21
(dd, 1H, J4,5 ꢀ 10.2, J5,6 ꢀ 3.5 Hz, H-5), 4.97 (ddd,
1H, J2,F ꢀ 46.4, J1,2 ꢀ 3.5, J2,3 ꢀ 9.8 Hz, H-2), 2.18,
2.15, 2.06, 2.01, 1.95 (s, 15H, 5 · CH3). 13C NMR
(62.9 MHz, CDCl3): d 171.4, 171.4, 171.4, 170.7, 170.5
(5 · C@O), 88.9 (d, JC,F ꢀ 188.6 Hz, C-2), 70.4 (s, C-
5), 68.1 (d, JC,F ꢀ 6.7 Hz, C-6), 70.4 (d, JC,F ꢀ 10.2 Hz,
C-4), 71.7 (d, JC,F ꢀ 21.0 Hz, C-3), 68.8 (d,
JC,F ꢀ 17.7 Hz, C-1), 20.5 (CH3); 19F{1H} NMR
References
1. Miethchen, R.; Neitzel, K.; Weise, K.; Michalik, M.;
Reinke, H.; Faltin, F. Eur. J. Org. Chem. 2004, 2010–
2018.
2. Posternak, T. Les Cyclitols; Hermann: Paris, 1962, Engl.
Ed. Holden-Day: San Francisco, 1965.
3. Hudlicky, T.; Cebulak, M. Cyclitols and Their Derivatives.
A Handbook of Physical, Spectral, and Synthetic Data;
VCH Weinheim: New York, Cambridge, 1993.
4. Takahashi, Y.; Nakayama, H.; Katagiri, K.; Ichikawa, K.;
Ito, N.; Takita, T.; Takeuchi, T.; Miyake, T. Tetrahedron
Lett. 2001, 42, 1053–1056, and papers cited therein.
5. Angyal, S. J.; Odier, L. Carbohydr. Res. 1980, 80, 203–
206.
6. Miethchen, R.; Sowa, Chr.; Frank, M.; Michalik, M.;
Reinke, H. Carbohydr. Res. 2002, 337, 1–9.
7. Miethchen, R.; Sowa, C.; Michalik, M. Tetrahedron Lett.
2001, 42, 8637–8639.
(235 MHz, CDCl3):
C16H21FO10 (392.34): C, 48.98; H, 5.40. Found: C,
49.23; H, 5.57.
d
À207.5. Anal. Calcd for
1.4.6. D-1,3,4-Tri-O-acetyl-2-deoxy-2-fluoro-5,6-O-[(S)-
2,2,2-trichloroethylidene]-chiro-inositol (18 endo-H)
and D-1,3,4-tri-O-acetyl-2-deoxy-2-fluoro-5,6-O-[(R)-2,2,2-
trichloroethylidene]-chiro-inositol (18 exo-H). The dia-
stereomeric fluoroinositols 51 (500 mg, 1.11 mmol) were
deprotected by HI to crude product 17a,b and then lat-
ter acetylated to 18 as described in the general proce-
dures 1.3 and 1.4. The acetyl derivatives were
separated by column chromatography (gradient: hep-
tane/EtOAc 5:1 ! heptane/EtOAc 1:1) yielding 370 mg
(76%) of 18 (endo-H); colourless amorphous solid
(cyclohexane), mp 47–49 ꢁC, Rf 0.26 (1:1 heptane/
EtOAc), and 55 mg (11%) of 18 (exo-H); colourless
amorphous solid, Rf 0.23 (1:1 heptane/EtOAc).
8. Kozikowski, A. P.; Powis, G.; Fauq, A. H.; Tuckmantel,
¨
W.; Gallegos, A. J. Org. Chem. 1994, 59, 963–971.
9. IUPAC Commission on the Nomenclature of Organic
Chemistry and IUPAC-IUB Commission on Biochemical
Nomenclature. Nomenclature of Cyclitols. Recommenda-
tions, 1973. Pure Appl. Chem. 1974, 37, 285–297.
10. Miethchen, R. J. Carbohydr. Chem. 2003, 22, 801–825.
11. Angyal, S. J.; Hoskinson, R. M. Methods Carbohydr.
Chem. 1963, 2, 87–89.
12. Lichtenthaler, F. W.; Emig, P. Carbohydr. Res. 1968, 7,
121–137.
13. Paulsen, H.; Ho¨hne, H. Chem. Ber. 1972, 105, 3445–3455.
14. Dangschat, G.; Fischer, H. O. L. Carbohydr. Res. 1987,
164, 343–355.
1
Compound 18 (endo-H form): H NMR (500 MHz,
CDCl3): d 5.59 (ddd, 1H, J1,F ꢀ 18.2, J1,2 ꢀ 2.8,
J1,6 ꢀ 4.0 Hz, H-1), 5.49 (s, 1H, CHCCl3), 5.33 (ddd,

748
R. Miethchen et al. / Carbohydrate Research 340 (2005) 741–748
15. Schedler, D. J. A.; Baker, D. C. Carbohydr. Res. 2004,
339, 1585–1595.
16. Hudlicky, T.; Entwistle, D. A.; Pitzer, K. K.; Thorpe, A. J.
Chem. Rev. 1996, 96, 1195–1220.
19. Kvic˘ala, J.; Paleta, O. Dehalogenation. In Houben-Weyl,
Methods of Organic Chemistry, Vol. E 10b/Part 2 (Org-
ano-Fluorine Compounds); G. Thieme: Stuttgart, 2000, pp
125–161.
´
17. Jacobsen, S.; Sløk, F. Acta Chem. Scand. 1993, 47, 1012–
1018.
20. Forsen, S.; Lindberg, B.; Silvander, B.-G. Acta Chem.
Scand. 1965, 19, 359–369.
18. Paleta, O. Replacement of Fluorine by Hydrogen. In
Houben-Weyl, Methods of Organic Chemistry, Vol. E 10b/
Part 2 (Organo-Fluorine Compounds); G. Thieme: Stutt-
gart, 2000, pp 306–344.
21. Miethchen, R.; Pundt, T.; Michalik, M. Tetrahedron Lett.
2005, 46, 831–833.
22. Karplus, M. J. Chem. Phys. 1959, 30, 11–
15.