Rearrangements in the course of fluorination by diethylaminosulfur trifluoride at C-2 of glycopyranosides: Some new parameters

Article abstract of DOI:10.1007/s007060200019

Reaction of a series of 21 glycosides unprotected at O-2 and featuring various configurations with DAST (diethylaminosulfur trifluoride) was monitored by ¹⁹F NMR spectroscopy. By means of the diacritical set of data (shift values and coupling c

Full text of DOI:10.1007/s007060200019

Monatshefte fuÈr Chemie 133, 427±448 ꢀ2002)
Rearrangements in the Course
of Fluorination by Diethylaminosulfur
Tri¯uoride at C-2 of Glycopyranosides:
Some NewParameters
Ã
Thomas Purkarthofer, Martin Tscherner, and Hansjorg Weber
Karl Dax , Martin Albert, David Hammond, Carina Illaszewicz,
È

Institut fur Organische Chemie, Technische Universitat Graz, A-8010 Graz, Osterreich


Summary. Reaction of a series of 21 glycosides unprotected at O-2 and featuring various
con®gurations with DAST ꢀdiethylaminosulfur tri¯uoride) was monitored by 19F NMR spectroscopy.
By means of the diacritical set of data ꢀshift values and coupling constants) thus obtained for each
product, identi®cation of the operative mechanisms was possible. By correlation of these ®ndings
with stereochemical details from the structure of the educts, new parameters governing the choice of
the reaction paths could be deduced. This evaluation led to the result that ring contraction after attack
at C-2 of the ring oxygen and entry of the ¯uoride at C-1 is strongly favoured over all other
possibilities. Exceptions are all derivatives of the manno series as well as all members of the trans-
decalin type structure as present after 4,6-O-benzylidene acetal formation with educts having their
ring substituents at C-4 and C-5 in diequatorial ꢀtrans) orientation. From these, ꢀ-D-mannopyrano-
sides generally and of the trans-decalin types those with an additional 1,2-trans-con®guration are
prone to 1,2-aglycon migration and, again, entry of the ¯uoride at C-1. Additional pathways like
alkoxy group migration, substitution under retention of con®guration, or orthoester formation, are
possible by participation of a suitably located neighbouring group at C-3 inasmuch as an alkoxy
group interferes from an antiperiplanar orientation to the leaving group at C-2 and an acyloxy
functionality attacks in a diequatorial relationship to the latter. The generally intended nucleophilic
substitution by ¯uoride under inversion of con®guration is of minor importance.
Keywords. Glycosides; Nucleophilic substitution; Fluorination; Rearrangements; Neighbour group
participation; 19F NMR spectroscopy; DAST.
Introduction
Within the carbohydrates, the so-called deoxy¯uoro analogues which contain
¯uorine instead of a hydroxyl group are of special importance in biological
studies [1]. Thus far, they have served, for example, as mechanistic probes to
investigate receptor-substrate interactions, attachment sites of antibodies, speci®ty
of enzymes, or metabolism and transport phenomena. For the stereoselective
Ã
Corresponding author. E-mail: dax@orgc.tu-graz.ac.at

428
K. Dax et al.
Scheme 1
chemical synthesis of these species, most frequently the principle of a nucleophilic
displacement reaction with concomitant inversion of con®guration ꢀSN2) is
employed. This consists, as generally depicted in Scheme 1, either of the treat-
ment of a sulfonate ꢀtri¯uoromethanesulfonate, tri¯ate) with ¯uoride anion or of
the direct reaction of an unprotected alcohol with diethylaminosulfur tri¯uoride
ꢀDAST ).
However, side reactions, many of them caused by neighbouring group ꢀNG)
participation, are often involved in such intended transformations [2±4]. Own
unsuccessful efforts towards the synthesis of certain 2-deoxy-2-¯uoro sugars
applying the SN2-strategy initiated attempts to categorize the set of hitherto
observed reaction pathways in such nucleophilic displacement reactions for all
non-glycosidic positions in carbohydrates [5]. From these, the structural pre-
requisites for the individual types of side reactions seemed evident:
i) Any vicinal alkoxy group oriented antiperiplanar to the leaving group ꢀLG)
ꢀincluding that containing the ring oxygen) may, under inversion of con®gu-
ration at the reaction centre, cause formation of an intermediate oxiranium ion
ꢀanchimeric assistance of the `simple' type, Scheme 2). The oxiranium ion is
opened, again under inversion of con®guration, by the nucleophile at one of the
carbons involved.
ii) A vicinal acyloxy group is able to interfere, with inversion of con®guration, by
attack of its carbonyl oxygen under formation of a cyclic acyloxonium ion
ꢀ`complex' type, Scheme 3). The steric requirement is the diequatorial ar-
rangement of both partners. The reaction is completed by attack of the external
nucleophile at one of the carbons involved.
iii) Out of an antiperiplanar orientation relative to the LG, a hydrogen atom or an
alkyl group ꢀincluding parts of the sugar ring) may shift to the reaction centre
with entry of the external nucleophile at the other end under inversion of
con®guration at both centres.
iv) As ¯uoride also may act as a base, in case of educts containing an axially
oriented LG together with a vicinal trans-located hydrogen atom elimination
ꢀE) is often observed.
v) Fragmentation ꢀF) may occur with the prerequisite that a well-stabilized
ꢀoxo)carbenium ion can be eliminated from the C-atom vicinal to that bearing
the LG. This is usually the case with the anomeric centre in educts that contain
the LG in equatorial position at C-3.

Fluorination of Glucopyranosides with DAST
429
Scheme 2
Scheme 3. Hy ˆ hydrolysis, AcM ˆ acyl migration
Generally it should be noted that mechanistic concertedness in the course of
these reactions manifests itself by the stereochemical homogeneity of the product,
whereas formation of structures effected by epimerization at one single centre
points to the existence of intermediates; this is especially the case when the stabi-
lized oxocarbenium ion containing C-1 is involved.

430
K. Dax et al.
For the sake of clarity, within this account the following symbols [5] for the above cited mechanisms
which involve neighbouring proup participation will be used:
AS: Anchimerically assisted substitution with retention of con®guration at the position of the
original activation
MS: Substitution by migration of the participating group and entry of the nucleophile ꢀ¯uo-
ride) at the position where the participating group departs with inversion of con®guration at both
centres
IS: Intramolecular nucleophilic substitution with inversion of con®guration by a hetero atom of
an NG under formation of a ꢀsmall) heterocyclic ring ꢀ`simple' type)
ISC: Intramolecular substitution by the carbonyl oxygen of a vicinal acyl group under inversion
of con®guration at the position of the original activation and entry of the nucleophile at the carbon of
the original carbonyl group to form an orthoester derivative ꢀ`complex' type)
In all instances, the position of activation in the sugar ring as well as the type of the participating
group ꢀ`H' for hydrogen, `NG' for any neighbouring group, `rO' for ring oxygen) and its location in
the educt are given in parentheses.
For the respective reactions at C-2 of glycopyranosides, the inventory of published
data comprises the following reaction paths:
i) Straight SN2-displacement is rather the exception than the rule; modest to good
results are obtained with educts of ꢁ-D-manno- and ꢁ-D-gluco-con®gurations
only. The disposition of the ꢀ-D-gluco-anomer to give this reaction is restricted to
structures containing a 4,6-O-benzylidene protection ꢀTable 1, entries 1±3).
ii) 2-Tri¯ates of ꢀ-D-mannopyranosides are prone to elimination under forma-
tion of 2,3-unsaturated products upon treatment with ¯uoride anion ꢀTable 1,
entry 4).
iii) The corresponding DAST-reaction with the OH-2 unprotected ꢀ-D-mannopy-
ranoside 1 causes 1,2-aglycon migration, MSꢀ2,NG-1), with concomitant
entry of the ¯uoride at C-1 under formation of the corresponding 2-O-methyl-
D-glucopyranosyl ¯uorides 2 ꢀTable 1, entry 5).
iv) Treatment of methyl 3-azido-4,6-O-benzylidene-3-deoxy-ꢀ-D-altropyrano-
side ꢀ3) with DAST ꢀTable 1, entry 6) results in ASꢀ2,NG-3 and=or NG-1)
ꢀsubstitution at C-2 with retention of con®guration to form 4) together with
MSꢀ2,NG-3) and MSꢀ2,NG-1) which produce benzyl 2-azido-2,3-dideoxy-3-
¯uoro-ꢀ-D-glucopyranoside 5 and 3-azido-2-O-benzyl-3-deoxy-D-allopyrano-
syl ¯uorides 6, respectively.
v) 2-Tri¯ates of 6-deoxy-L-galactopyranosides ꢀfucopyranosides, 7), independent
of the anomeric con®guration, give ring contraction, MSꢀ2,rO), to form 2,5-
anhydro sugars 8 with inversion of con®guration at C-2 and entry of ¯uorine at
C-1 ꢀTable 1, entry 7). This special type of side reaction is frequently observed
with educts of galacto- and arabino-con®gurations when other nucleophiles
than ¯uoride are applied.
In reactions of carbohydrate 2-tri¯ates with other nucleophiles and in ꢀmech-
anistically closely related) nitrous acid deaminations of 2-amino-2-deoxy sugars
the following additional pathways have been observed:
i) Hydride shift, MSꢀ2,H-3), occurred in the course of a diazotation reaction of
methyl ꢀ-D-mannosaminide under formation of a 2-deoxy-3-ulose ꢀTable 2,

Fluorination of Glucopyranosides with DAST
431
entry 1; this reaction formally corresponds to an elimination followed by retro-
enolization). Additionally, aglycon migration took place.
ii) Alkyl shift, MSꢀ2,C-4), was found with a nitrous acid deamination of methyl ꢀ-
and ꢁ-D-glucosaminide to give a pentofuranose derivative with a formyl side
Table 1. Results from attempted ¯uorinations at C-2 of pyranosides ꢀTBAF ˆ tetrabutylammonium ¯uoride)
Educt
Productꢀs)=Mechanism
Conditions
Yield=%
Ref.
[6]
DAST
1
2
diglyme
100ꢀC, 7 min
77
TBAF, MeCN
30
[7]
re¯ux, 2.5 h
3
4
TBAF, MeCN
77
82
[7]
[8]
re¯ux, 80 min
TBAF, MeCN
re¯ux, 30 min
5
DAST
diglyme
100ꢀC, 30 min
76
[9]
40
ꢀAS)
6
DAST, benzene
40
re¯ux, 2 h
ꢀMSꢀ2,NG-3)) [10]
15
ꢀMSꢀ2,NG-1))
7
3HF Á TEA, TEA,
MeCN, room
60
[11]
temperature, 16 h

432
K. Dax et al.
chain ꢀthe former C-3) at C-2; this product was subject to epimerization at C-2
ꢀTable 2, entries 2 and 3). The `conventional' ring contraction, MSꢀ2,rO)
ꢀcompare Table 1, entry 7) was the main reaction.
iii) Orthoester formation, ISCꢀ2,NG-3), resulted from a trans-diequatorial ar-
rangement between the tri¯ate and an acyloxy group at C-3 ꢀScheme 2,
entry 4); the intermediate acyloxonium ion was partly hydrolyzed to a
mixture of the respective 2- and 3-benzoate with inverted con®guration at
C-2.
Table 2. Further side reactions upon attempted nucleophilic substitution at C-2 of pyranosides
Educt
Productꢀs)=Mechanism
Conditions
Yield=%
Ref.
NaNO2,
50
1
2
HOAc=H2O
room
ꢀMSꢀ2,H-3)) [12]
30
temperature, 2 h
ꢀMSꢀ2,NG-1))
27
ꢀMSꢀ2,C-4)) [13]
73
NaNO2 ꢀpH ˆ 3.5)
room temperature,
12 h
ꢀMSꢀ2,rO))
16
3
4
ꢀMSꢀ2,C-4))
84
[13]
[14]
ꢀMSꢀ2,rO))
MeOH,
sym-collidine,
toluene,
90
91
re¯ux, 6 h
5
[15]
MeLi, Et2O,
À50ꢀC ! room
temperature, 1 h
6
77
[15]

Fluorination of Glucopyranosides with DAST
433
Scheme 4
iv) ꢀ-Hydrogen abstraction has recently been proven in experiments with
deuterated educts by El Nemr and Tsuchiya [15] to be the initial step in the
reaction of carbohydrate tri¯ates with strong bases ꢀalkyl lithium compounds).
Thus, from the 2-tri¯ates 9 and 10 of otherwise fully and identically protected
ꢀ-D-gluco- and ꢀ-D-mannopyranoside, the same 2-C-alkyl derivative with
D-gluco-con®guration ꢀ11, Table 2, entries 5 and 6) was obtained. The whole
set of products formed and the mechanisms involved for their formation is
shown in Scheme 4 with the ꢁ-D-manno-educt 12, where ± besides unsaturated
products ± mixtures of 2-C-alkyl derivatives with D-gluco-ꢀ13) as well as
D-manno-con®guration ꢀ14) were formed due to the missing steric approach
control in the ®nal addition step.
Although this compilation sheds some light on the complex situation and even
immediately allows the identi®cation of a few seemingly contradictory results in the
literature, a series of questions concerning the precise dependence on structural
features has remained. Within this contribution we focus on the governing
parameters for the most fascinating competitors, MSꢀ2,rO) and MSꢀ2,NG-1). Can
these be made comprehensible when educts are used which ± under the aspect of
conformational ¯exibility ± ful®ll the stereochemical prerequisites for both
possibilities?
As the collection of NMR data for all types of ¯uorinated reaction products
obtained thus far in attempted syntheses by nucleophilic displacement reac-
tions at C-2 had made available a set of diacritical 19F NMR parameters
ꢀTable 3), the stage was set to conduct ± under comparable conditions ± a more

434
K. Dax et al.: Fluorination of Glucopyranosides with DAST
Table 3. Characteristic 19F NMR data
Operative
Type of structure
ꢂ=ppm
2JF,H=Hz
mechanism
MSꢀ2,rO)
134±143
135±150
63±68
48±54
MSꢀ2,NG-1)
SN2
or
ASꢀ2,NG-1=3)
190±220
47±54
MSꢀ2,NG-3)
comprehensive study simply by monitoring the crude reaction mixtures by 19F
NMR spectroscopy.
Results and Discussion
The ®rst aim in these studies was to reexamine the reported ꢀbut by no means
substantiated) 1,2-aglycon shifts, MSꢀ2,NG-1), from DAST-treatment of 2-OH-
unprotected educts of ꢀ-L-arabino- and ꢁ-D-galacto-con®guration, respectively,
containing a 3,4-O-isopropylidene group [16]. In contrast to this ꢀand completely
provable), the 2-sulfonates of similar compounds from the ꢀ-L- ꢀTable 1, entry 7
[11]) as well as the ꢁ-D-galacto-series [17, 18] had been found to give ring con-
traction, MSꢀ2,rO), on attempted nucleophilic displacements. When taking into
account some conformational ¯exibility of these educt structures, the given 1,2-
trans-orientation allows an antiperiplanar arrangement of LG and the respective
migrating NG as the stereochemical prerequisite for both types of reactions.
However, as can be seen from Table 4, entries 1 and 6, the DAST-treatment, under
identical conditions as described [16] ꢀin dichloromethane, 3 equivalents of DAST,
room temperature), of benzyl 3,4-O-isopropylidene-ꢀ-D-arabinopyranoside ꢀ15, the
enantiomer of the original educt [16]) as well as methyl 3,4-O-isopropylidene-6-O-
trityl-ꢁ-D-galactopyranoside ꢀ23) caused MSꢀ2,rO) only. In full agreement with
previous ®ndings [11, 17, 18] with sulfonate displacement reactions, the same pairs
of ring-contracted products ꢀbut in differing individual ratios) were formed when
the respective anomer ꢀ16 or 22; Table 4, entries 2 and 5) was reacted. MSꢀ2,rO)
was also exclusively observed when methyl 3,4-O-isopropylidene-ꢁ-D-arabinopy-
ranoside ꢀ18, Table 4, entry 3) or its 2-tri¯ate were treated with DAST and
tetrabutylammonium ¯uoride, respectively. To elucidate any conformational barrier
in the obviously clear-cut preference for MSꢀ2,rO) over MSꢀ2,NG-1), we turned to
the ꢀ1,2-trans-con®gured) educts 20 ꢀꢁ-D-ribo) as well as 25 and 27 ꢀꢀ-D-altro)
which ± in comparison to the structures 15 and 23 ± show inverted con®gurations

Table 4. Reactions with DAST
Educt
Proposed structure
of products
19F NMR
ꢂ=ppm
J=Hz
1H NMR
ꢂ=ppm
J=Hz
13C NMR
ꢂ=ppm
J=Hz
Operative
mechanism
1
2
À140.0
67=26
H-1: 5.39
C-1: 111.2
219.8
66.9=2.0
MSꢀ2,rO)
À134.2
63=5
H-1: 5.37
C-1: 109.3
220.7
63.4=2.6
À141.3
67=24
H-1: 5.23
C-1: 114.2
222.9
3
4
67.4=2.1
MSꢀ2,rO)
À135.5
64=9
H-1: 5.18
C-1: 112.6
223.4
63.6=2.7
À138.6
67=6
H-1: 5.34
C-1: 112.8
220.6
68.8=6.9
MSꢀ2,rO)
À138.0
64=5
H-1: 5.42
C-1: 111.7
214.3
62.8=7.0
5
6
À140.8
67=24
H-1: 5.25
C-1: 113.4
220.5
67.8=1.8
MSꢀ2,rO)
À135.4
64=6
H-1: 5.19
C-1: 111.7
220.4
63.3=2.6
À142.7
67=15
H-1: 5.24
C-1: 111.8
220.7
66.4=3.3
7
MSꢀ2,rO)
À136.9
64=6
H-1: 5.19
C-1: 111.9
219.7
64.6=4.1
À143.3
67=18
H-1: 5.18
C-1: 111.6
220.9
66.8=2.2
8
MSꢀ2,rO)
À137.5
64=9
H-1: 5.13
C-1: 111.4
219.8
64.2=3.1
ꢀcontinued)

436
K. Dax et al.
Table 4 ꢀcontinued)
Educt
Proposed structure
of products
19F NMR
ꢂ=ppm
J=Hz
1H NMR
ꢂ=ppm
J=Hz
13C NMR
Operative
ꢂ=ppm
J=Hz
mechanism
À142.4
67=21
H-1: 5.18
C-1: 112.4
222.1
66.8=2.6
MSꢀ2,rO)
À136.8
64=5
H-1: 5.16
63.7=3.1
H-1: 4.62
13.6
not resolved
9
C-1: 97.3
34.7
À196.5
SN2
47=12=7
H-2: 4.60
45=3
C-2: 85.2
176.8
or
ASꢀ2,rO)
À142.3
66=14
H-1: 5.27
C-1: 112.3
219.2
67=2
10
11
12
MSꢀ2,rO)
MSꢀ2,rO)
MSꢀ2,rO)
À143.2
64=13
H-1: 5.26
C-1: 111.4
219.3
63.7=1.8
À141.9
66=16
H-1: 5.41
C-1: 112.5
221.5
66.0=2.1
À140.2
64=not
resolved
H-1: 5.39
C-1: 111.5
220.3
63.8=2.8
À141.9
67=18
H-1: 5.44
C-1: 110.2
221.7
66.8=1.8
À136.9
64=6
H-1: 5.41
C-1: 109.7
219.4
63.7=2.4
aldehyde, after
À138.5
67=15
hydrolysis at C-1
13
14
À134.7
67=9
H-1: 9.77
C-1: 202.9
MSꢀ2,rO)
MSꢀ2,rO)
À135.9
67=15
H-1: 5.45
C-1: 111.6
221.7
65.5=3.5
À132.4
67=9
H-1: 5.41
C-1: 111.6
222
66.4=6.2
ꢀcontinued)

Fluorination of Glucopyranosides with DAST
Table 4 ꢀcontinued)
Educt
437
Proposed structure
of products
19F NMR
ꢂ=ppm
J=Hz
1H NMR
ꢂ=ppm
J=Hz
13C NMR
ꢂ=ppm
J=Hz
Operative
mechanism
ꢀ-anomer
À148.1
52=27
ꢀ-anomer
5.70
ꢀ-anomer
105.6
52.0=2.9
229.7
15
MSꢀ2,NG-1)
ꢁ-anomer
À135.6
55=12
ꢁ-anomer
5.29
ꢁ-anomer
109.5
53.5=6.2
218.2
H-1: 5.50
À139.2
49.5=1.8
C-1: 106.7
224.7
MSꢀ2,NG-1)
16
49=not resolved
H-2: 3.62
1.8=1.5
À148.4
56=11
H-1: 5.54
C-1: 99.9
217.4
55.8=5.6
MSꢀ2,rO)
À147.4
57=12
H-1: 5.55
C-1: 99.5
220
17
57=4
À135.7
MSꢀ2,NG-1)
50
not detected not detected
18
À126.0
H-1: 5.78
C-1: 108.4
225.7
MSꢀ2,NG-1)
52
52.3=1.7
C-2: 52.3
28.0
À147.8
53=23
19
not detected not detected MSꢀ2,NG-1)
À138.0
53=12
ꢀcontinued)

438
K. Dax et al.
Table 4 ꢀcontinued)
Educt
Proposed structure
of products
19F NMR
ꢂ=ppm
J=Hz
1H NMR
ꢂ=ppm
J=Hz
13C NMR
Operative
ꢂ=ppm
J=Hz
mechanism
H-1: 4.91
3.6
C-1: 98.8
±
H-1: 4.90
3.6
C-1: 99.5
20
À142.5
66=10
not detected not detected MSꢀ2,rO)
À136.2
67=not resolved
À139.0
49=14
61
unknown
not detected not detected unknown
À192.5
not detected C-1: 99.2
34.5
ASꢀ2,NG-3=1)
43=10=10
21
À199.0
not detected C-1: 99.6
9.6
MSꢀ2,NG-3)
54=10=10
À122.1
67=6
H-1: 5.85
C-1: 105.6
22
65.9=1.5=1.5 225.5
MSꢀ2,NG-1)
H-1: 5.58
62.5
À127.8
61=À
H-2: 4.00
ꢀs)
C-1: 106.3
227.8
H-1: 5.06
ꢀs)
C-1: 98.7
23
ISCꢀ2,NG-3)
±
±
H-1: 5.02
ꢀs)
C-1: 98.9
C-1: 99.9
ISCꢀ2,NG-3)
H-1: 4.85
ꢀs)
‡ Hydrolysis

Fluorination of Glucopyranosides with DAST
439
at C-1 as well as C-2. However, MSꢀ2,rO) was found to be the sole reaction in all
three cases ꢀTable 4, entries 4, 7, and 8).
So far, in this series all educts contained a 3,4-cis-con®guration and were, in
this part of the molecule, also uniformly protected by the isopropylidene group. To
test the in¯uence of the latter, the conformationally more rigid methyl 3,4-anhydro-
6-O-trityl-ꢀ-D-galactopyranoside ꢀ29) was studied; in this case ꢀTable 4, entry 9),
besides the 19F NMR signals for the products 30 of the MSꢀ2,rO)-reaction, that of
31 stemming from SN2 or ASꢀ2,rO) appeared ꢀÀ196.4 ppm, 47=12=7 Hz). Sub-
sequently, turning to the 3-O-protected derivatives of methyl 4,6-O-benzylidene-ꢁ-
D-galactopyranoside, both benzyl ether 32 and benzoate 34 ꢀTable 4, entries 10 and
11) were found to be subjects of MSꢀ2,rO) exclusively. From the treatment of the
2-tri¯ate of 34 with aliphatic alcohols in the presence of an organic base, formation
of ꢀthe pair of) 2,3-orthoesters under inversion of con®guration at C-2 has been
claimed [14]. However, this reaction only had been proven with the ꢁ-D-gluco-
analogue ꢀsee Table 2, entry 4). Thorough NMR measurements ꢀprivate com-
munication of the original authors) recently showed that the products are ± as had
been anticipated [5] ± structural analogues of compounds 35 ꢀTable 4, entry 11).
Thus, even under these conditions, MSꢀ2,rO) is preferred over ISCꢀ2,NG-3).
To complete these extensive arabino=ribo- as well as galacto=altro-series and to
start in the gluco=manno-range, a few not dioxolane ring protected derivatives of
both were treated with DAST. Again ꢀTable 4, entries 12 and 13), benzyl 3,4,6-tri-
O-benzyl-ꢁ-D-galacto- ꢀ36) as well as the identically protected ꢁ-D-glucopyrano-
side ꢀ38) were subject to MSꢀ2,rO). In the crude reaction mixture of 38 and DAST,
a small proportion of benzyl ¯uoride ꢀtriplet at À206.6 ppm, 49 Hz) was also
detected. During the standard isolation of the primary products, obviously hy-
drolysis at C-1 occurred under liberation of the aldehydo-2,5-anhydro-D-hexose
derivative 40. The disaccharidic educt 41, consisting of an ꢀ-D-glucopyranosyl
moiety with an unprotected OH-group at C-2 as donor and a 1,2:3,4-di-O-iso-
propylidene-ꢀ-D-galactopyranose as acceptor, was subject to this dominant type of
side-reaction ꢀTable 4, entry 14).
This MSꢀ2,rO)-side reaction was also observed with 2-tri¯ates of alkyl 3,4,6-tri-O-benzyl-ꢀ- and
ꢁ-D-glucopyranosides under hydrolytic conditions ꢀwater=pyridine in DMF, 160ꢀC, 5 min) and was
used [19] for glycoside cleavage in the synthesis of chiral cyclopropylmethanol derivatives.
Nevertheless, a parallel SN2-reaction by ¯uoride was also observed upon treatment of the tri¯ate of
38 with TBAF in THF [20].
In contrast to the ®ndings described above, where MSꢀ2,rO) was the generally
dominating option, treatment of the corresponding derivatives from the ꢀ-D-
manno-series containing an unprotected OH-2 with DAST is known [2, 3] to induce
aglycon migration, MSꢀ2,NG-1). This tendency is not restricted to 4,6-O-ben-
zylidene protected educts ꢀsee Table 1, entry 5 [9]), but also dominates in cases
where a cyclic acetal protection group is absent [16, 21, 22].
To validate our approach, methyl 3-O-benzyl-4,6-O-benzylidene-ꢀ-D-manno-
pyranoside ꢀ1) was subjected to reaction with DAST under our standard conditions,
and the results ꢀꢀMSꢀ2,NG-1) as well as NMR data of product 2 ꢀTable 4, entry 15))
were found to be in full agreement with the published ones from the DAST-reaction
in diglyme at 100ꢀC [9].

440
K. Dax et al.
Yield=%
50
Table 5. Related reactions
Educt
Product
NMR data
Ref.
[23]
ꢂ=ppm, J=Hz
1
2
no data
no data
88
86
[16]
[16]
ꢀ-anomer:
H-1: 5.34 ꢀ53.2=5.9)
ꢁ-anomer:
H-1: 5.54 ꢀ51.5=2.3)
3
F-1: À144.3 ꢀ62.4=6.0)
F-2: À118.9 ꢀm)
H-1: 5.32 ꢀ62.4=1.2)
19
[27]
4
C-1: 106.2 ꢀ224.2=46.2)
C-2: 110.3 ꢀ223.3=25.8)
The corresponding ꢁ-D-gluco-derivative 43 contains, in its 4C1-conformation, an
antiperiplaner orientation of the LG to the ring oxygen ꢀrO) and a diequatorial one to
the aglycon ꢀNG-1). Due to 4,6-O-benzylidene protection it constitutes a rigid trans-
decalin system. Thus far, for the displacement reactions of the corresponding
tri¯ates, SN2 had been the choice [7]; the possible MSꢀ2,rO), observed with educts
devoid of this `paralyzing' dioxane protection [19, 20], had never come into play1.
However, there is a single report in the literature dealing with the nitrous acid
deamination with methyl 2-amino-4,6-O-benzylidene-2-deoxy-ꢁ-D-glucopy-
ranoside ꢀ45) of this trans-decalin type ꢀTable 5, entry 1) [23] where from the
elucidation of the product structure ꢀthat time by chemical means only) this
MSꢀ2,rO) had to be anticipated. In later experiments [24], isolation of the same
product, 2,5-anhydro-4,6-O-benzylidene-D-mannose ꢀ46), from the corresponding
benzyl glycoside could not be achieved ꢀbut its formation was not explicitly
excluded).
In our case, against all expectations, the treatment of 43 with DAST caused
aglycon migration, MSꢀ2,NG-1), under formation of 3-O-benzyl-4,6-O-benzyli-
dene-2-O-methyl-ꢀ-D-mannopyranosyl ¯uoride ꢀ44). For an explanation it can be
argued that the centres involved in this rearrangement are located at the more ¯exible
1
See Note Added in Proof at the end of this contribution

Fluorination of Glucopyranosides with DAST
441
part of the trans-decalin system, thus possibly allowing quasi-diaxial arrangement of
LG and NG-1 ꢀas depicted in Table 4, entry 16). Furthermore it has been reported in
the literature [16] that thioglycosides in the ꢁ-D-gluco- and ꢁ-D-galactopyranose
series ꢀas well ꢁ-D-galactopyranosyl azides) with unprotected OH-2, on treatment
with DAST, give this MSꢀ2,NG-1) in excellent yields ꢀe.g. the phenyl thioglycosides
47 and 49 of the ꢁ-D-gluco-series shown in Table 5, entries 2 and 3).
To prove this exceptional migratory aptitude of the alkyl=arylthio as well as the azido group as
compared to the aglycon of normal O-glycosides ꢀe.g. 38), azide 51 and thioglycoside 54 were
treated with DAST under standard conditions. The results shown in Table 4, entries 17 and 18, give
the impression that this report for the phenylthio group may be valid1 ꢀhowever, the given J1,2 value
of 5.9 Hz for the ꢀ-anomer of 2-phenylthio-mannopyranosyl ¯uoride 50 [16] cannot be imagined to
be possible), whereas those from the azido-analogue could not be reproduced since a 10:1-preference
for the MSꢀ2,rO)-product 52 over that of the MSꢀ2,NG-1)-reaction ꢀ53) was observed. As is evident
from the literature [25], the geminal 19F, 1H couplings for derivatives containing an azido or arylthio
substituent are by approximately 8±10 Hz smaller than the corresponding values in case of
O-substitution.
The incorporation of the hexopyranose moiety into a trans-decalin ring system
as in the 4,6-O-benzylidene protected educt 43 of the gluco-series obviously causes
the exceptional reactivity order that the otherwise generally preferred MSꢀ2,rO)1 is
`prohibited', whereas ꢀdue to 1,2-trans-con®guration) MSꢀ2,NG-1) is `allowed',
even when a diequatorial orientation of LG and NG predominates. With the
intention to bring the bridgeheads of the trans-annellation closer to the reaction
centre, we chose the butane 2,3-bis-acetal ꢀBBA) strategy [26] to simultaneously
protect the diequatorial arranged OH-groups at C-3 and 4 in methyl ꢀ-D-manno-
and -glucopyranoside. The corresponding educts, 56 and 58, behaved as follows
ꢀTable 4, entries 19 and 20): The ꢀ-D-manno-isomer 56 solely gave the expected
MSꢀ2,NG-1)-products 57 ꢀan identical result has very recently been published [27]
with the corresponding cyclohexane diacetal ꢀCDA) from the ꢀ-L-manno-series).
However, the ꢀ-D-gluco-analogue 58, under standard reaction conditions, led to at
least eleven ¯uorinated products, most of them showing the characteristic 19F
NMR features of ring-contracted structures. Only when the reaction rate was
drastically reduced ꢀby conducting the treatment with DAST at À20ꢀC in the
presence of an excess of pyridine), formation of one single product could be
observed by TLC monitoring. After isolation, it did not contain ¯uorine but a
diethylamino moiety. From the similarity of the NMR spectra to those of the
starting material 58 ꢀexcept chemical shift values for H-2 and H-3), its structure
was anticipated to be that of the two ꢀdiastereomeric) 2-O-diethylaminosul®nyl
derivatives 59 ꢀformed by hydrolysis of both S±F-bonds in the intermediate of the
DAST-reaction, see Scheme 1). The distinct results presented in Table 4, entry 20,
were then obtained after prolonged reaction time under these conditions. MSꢀ2,rO)
to give 60 clearly dominated ꢀcompare results from the DAST-treatment of a
structurally related 2-ulose 62 bearing a 3,4-CDA protection [27], where ring
contraction was observed; Table 5, entry 4). For the additionally observed signal
ꢀꢂ ˆ À139.0 ppm, J ˆ 49 and 14 Hz), which corresponds to a glycosyl ¯uoride,
presently no structure can be suggested ꢀ61). However, it proved, by the admixture
of the reaction products 57, not to be identical with the ꢁ-anomer of 2-O-methyl-
glucopyranosyl ¯uoride 57 ꢀꢂ ˆ À138.0 ppm, J ˆ 53 and 12 Hz). The latter was

442
K. Dax et al.: Fluorination of Glucopyranosides with DAST
formed in the DAST-reaction of 56 ꢀTable 4, entry 19), but its generation from 58
would have also been conceivable [24] as the opening of the intermediate
oxiranium ion in the MSꢀ2,rO)-mechanism by the neighbouring methoxy group
from C-1 under overall retention of con®guration.
Furthermore, two other educts were investigated, which both have a relatively
rigid conformation as well as an axial OH-group at C-2. In the ®rst case, with
methyl 3-O-benzyl-4,6-O-benzylidene-ꢀ-D-altropyranoside ꢀ64), two antiperipla-
nar oriented alkoxy groups are present in vicinal positions to the LG, whereas in
the second example, with 1,6-anhydro-3,4-O-isopropylidene-ꢁ-D-galactopyranose
ꢀ67), the oxygen atom of the 1,6-anhydro ring occupies the antiperiplanar position.
The results obtained with 64 ꢀTable 4, entry 21) parallel those from the corre-
sponding 3-azido-3-deoxy analogue 3 depicted in Table 1, entry 6, except that
aglycon migration ꢀMSꢀ2,NG-1)) having led to compound 6 was not observed in
this case. In comparison to the MSꢀ2,rO) reactions found with the educts 25 and 27,
both of ꢀ-D-altro-con®guration as well, the diacritical role of the protecting group
with respect to the necessary conformational interconversion becomes evident. As
expected, the DAST-treatment of 67 resulted in migrative substitution at C-2 by the
oxygen of the 1,6-anhydro ring with inversion of con®guration and entry of ¯uoride
at C-1 ꢀMSꢀ2,NG-1)) to yield 2,6-anhydro-D-talopyranosyl ¯uorides 68. Note-
worthy, the 19F NMR resonances are located at higher ®elds and show the same
magnitude of geminal couplings as characteristic for MSꢀ2,rO)-products. These
results are in good agreement with those reported from the DAST reaction of the
unprotected 1,6-anhydro-ꢁ-D-galactopyranose [28].
Finally, to test the SN2- vs. the ISCꢀ2,NG-3)-option, methyl 3-O-benzoyl-4,6-
O-benzylidene-ꢀ-D-glucopyranoside ꢀ69) was reacted with DAST ꢀTable 4, entry
23). Although TLC monitoring showed product formation, no discrete resonance
signal could be observed by 19F NMR. After work-up, the products were found to
be those of ISC ꢀ70) and subsequent hydrolysis ꢀ71) as well as ꢀnot shown in entry
23) the 2-O-diethylaminosul®nyl derivative of educt 69.
In conclusion, the following `rules', additional to those mentioned in the
introduction, can be derived from the results described herein on the treatment of
alkyl hexopyranosides containing an unprotected OH-group at C-2 with DAST in
dichloromethane at room temperature:
i) MSꢀ2,rO), the ring contraction under attack of the ring oxygen, is generally
preferred over all other possibilities, even when the predominating conforma-
tion does not contain OH-2 in the ꢀquasi-essential) equatorial position. This is
especially valid in the class of pento- and hexopyranosides which contain a
ꢀcis)-3,4-O-isopropylidene protecting group. Exceptions from this type of re-
action are all educts of the manno-series as well as those 4,6-O-benzylidenated
hexopyranosides which are members of the trans-decalin family ꢀderivatives of
the gluco-, allo-, and altro-series as they contain their ring substituents at C-4
and C-5 in ꢀtrans)-diequatorial orientation)1.
ii) MSꢀ2,NG-1), the so-called aglycon migration, seems to be the `opposite'
alternative to MSꢀ2,rO) as they, with O-glycosidic educts, have never been
observed together in the same reaction. Independently of the protecting groups
present, MSꢀ2,NG-1) ®nds its stage set for single action in all derivatives of
ꢀ-D-mannopyranoside.

Table 6. 13C NMR data ꢀꢂ=ppm, J=Hz); assignments marked with an asterisk may be interchanged
C-1
C-2
C-3
C-4
C-5
C-6
±
Others
17a
17b
19a
19b
21a
21b
26a
26b
28a
28b
31
111.2
219.8
84.8
80.9
3.6
81.5
74.7
71.7 ꢀBn), 112.5=26.6=25.0 ꢀCMe2)
21.0
109.3
220.7
84.3
29.4
80.8
81.4
82.1
82.0
81.5
81.5
82.4
82.8
81.9
82.3
48.6
74.3
74.5
74.8
74.7
81.2
80.7
78.5
75.3
71.0
68.7
74.7
75.2
75.2
74.1
74.2
84.8
85.2
83.3
83.7
65.3
73.3
73.3
73.6
73.6
±
71.3 ꢀBn), 112.5=26.6=25.0 ꢀCMe2)
57.7 ꢀOMe), 113.4=26.8=25.1 ꢀCMe2)
57.8 ꢀOMe), 113.6=26.8=25.1 ꢀCMe2)
57.9 ꢀOMe), 113.5=26.2=24.9 ꢀCMe2)
57.8 ꢀOMe), 113.5=26.3=25.0 ꢀCMe2)
114.2
222.9
85.3
21.5
81.4
3.5
±
112.6
223.4
84.9
29.5
81.3
±
112.8
220.6
82.7
22.2
81.3
6.2
±
111.7
214.3
82.2
35.8
80.8
±
111.8
220.0
84.7
24.9
80.8
3.5
64.4
64.8
63.9
64.3
63.3
67.6
67.5
67.3
67.3
68.8
68.8
68.6
68.6
62.0
61.9
57.5 ꢀOMe), 114.1=27.6=25.7 ꢀCMe2),
87.0 ꢀCPh3)
111.9
219.7
84.9
26.6
81.1
2.3
57.5 ꢀOMe), 113.8=27.6=25.7 ꢀCMe2),
87.0 ꢀCPh3)
111.6
220.9
84.5
24.0
80.5
3.8
57.6 ꢀOMe), 114.4=27.5=25.6 ꢀCMe2),
178.4=39.0=27.4 ꢀPiv)
111.4
220.7
85.1
29.4
80.7
1.5
57.6 ꢀOMe), 114.1=27.5=25.6 ꢀCMe2),
178.4=39.0=27.4 ꢀPiv)
97.3
34.7
85.2
51.0
24.4
55.4 ꢀOMe), 87.0 ꢀCPh3)
176.8
Ã
Ã
Ã
Ã
Ã
Ã
Ã
Ã
Ã
Ã
Ã
Ã
Ã
33a
33b
35a
35b
2ꢀ
111.4
219.3
80.6
25.0
79.2
57.5 ꢀOMe), 72.2 ꢀBn), 99.0 ꢀCHPh)
[n.r.]
Ã
112.3
219.2
80.7
22.0
79.2
57.4 ꢀOMe), 72.2 ꢀBn), 99.1 ꢀCHPh)
[n.r.]
111.2
221.3
79.8
23.3
74.4
4.0
57.5 ꢀOMe), 166.2 ꢀBz), 98.7 ꢀCHPh)
57.6 ꢀOMe), 166.2 ꢀBz), 98.7 ꢀCHPh)
60.2 ꢀOMe), 75.4 ꢀBn), 101.6 ꢀCHPh)
60.5 ꢀOMe), 74.7 ꢀBn), 101.5 ꢀCHPh)
60.9 ꢀOMe), 73.7 ꢀBn), 101.9 ꢀCHPh)
74.2=73.5=71.9 ꢀBn)
111.5
220.3
79.7
27.7
74.1
1.3
105.6
229.7
81.5
24.1
78.2
64.7
3.8
2ꢁ
109.5
218.2
83.3
24.1
79.6
8.8
65.6
44
106.7
224.7
78.3
35.6
75.6
2.7
66.3
2.7
Ã
Ã
55
108.4
225.7
52.3
28.0
77.8
2.7
74.2
3.7
Ã
Ã
Ã
58
99.9
69.5
70.2
66.4
66.8
55.3 ꢀOMe), 99.7=48.4=48.2=18.0=
17.8 ꢀBBA), 86.6 ꢀCPh3)
59a
98.8
69.9
68.2
54.9 ꢀOMe), 99.6=48.1=48.0=17.6=
17.5 ꢀBBA), 86.3 ꢀCPh3), 36.7=36.6=
14.0=13.9 ꢀNEt2)
59b
99.5
71.9
68.1
66.7
68.7
61.7
ꢀcontinued)

444
K. Dax et al.: Fluorination of Glucopyranosides with DAST
Table 6 ꢀcontinued)
C-1
C-2
88.2
C-3
72.2
C-4
C-5
C-6
Others
65
99.2
34.5
71.1
1.9
58.7
69.5
56.1 ꢀOMe), 73.6 ꢀBn), 102.6 ꢀCHPh)
174.2
27.2
66
99.6
9.6
80.0
16.9
91.4
77.2
61.8
69.1
60.8
63.0
69.1
69.1
69.0
55.7 ꢀOMe), 73.8 ꢀBn), 101.9 ꢀCHPh)
110.9=26.2=24.5 ꢀCMe2)
187.2
ꢁ15
69.9
ꢁ5
69.3
1.5
68a
68b
70a
70b
71
105.6
225.5
65.3
21.4
70.5
4.2
106.3
227.8
68.4
19.5
73.5
9.2
70.5
6.8
68.7
2.0
113.0=26.2=25.1 ꢀCMe2)
98.7
98.9
99.9
76.7
77.0
72.8
75.9
75.2
67.7
79.7
79.5
79.4
60.2
60.5
63.6
55.6 ꢀOMe), 102.0 ꢀCHPh), 121.0=51.2
ꢀorthoester)
55.6 ꢀOMe), 102.2 ꢀCHPh), 122.1=51.6
ꢀorthoester)
55.4 ꢀOMe), 102.5 ꢀCHPh), 166.4 ꢀBz)
iii) MSꢀ2,NG-1) is also operative in pyranoid educts with a 4,6-O-benzylidene
protection as soon as a 1,2-trans- as well as 4,5-trans-orientation of their
ring substituents is given ꢀꢀ-D-altro and ꢁ-D-gluco1; ꢁ-D-allo was not probed).
In the case of 4,6-O-benzylidene-ꢀ-D-altropyranosides, MSꢀ2,NG-3), the
migrative substitution ꢀ`simple' case) by the NG from C-3, as well as
ASꢀ2,NG-1 and=or 3), the anchimerically assisted substitution under reten-
tion of con®guration, become signi®cant as well.
iv) ISCꢀ2,NG-3), the participation of the `complex' type ꢀout of a diequatorial
arrangement to the LG) by a neighbouring acyloxy group, ranks behind a
possible MSꢀ2,rO) but before SN2.
v) SN2, the usually intended nucleophilic substitution under inversion of con®gu-
ration, is the reaction of choice with ꢁ-D-mannopyranosides only.
vi) E, elimination, was never observed, although many educts ful®lled the stereo-
chemical prerequisite of an antiperiplanar orientation between the LG and a
vicinal hydrogen atom at C-3 or C-1.
Synthesis of Educts
Many of the educts used in this study were taken either directly or in form of
essential precursors from the carbohydrate reference collection of this institute or
were gifts of Chemprosa Company, Lannach ꢀAustria). The eventually neces-
sary ®nal transformations on donated precursors as well as the syntheses of the
remaining educts were conducted according to literature procedures. The regio-
selective introduction of the butane bis-acetal protection in educt 58 was achieved
starting from the known methyl 2-benzoyl-ꢀ-D-glucopyranoside. All compounds
1
gave satisfactory H and 13C NMR spectra, but were not further characterized.

446
K. Dax et al.
Characterization of products
As in most cases the formed mixtures of diastereomers were found to be hardly
1
separable, unequivocal identi®cation of individual H and 13C NMR signals was
not possible in all instances; this was especially the case with proton resonance
spectra. Data essential for the structure assignments are included in Table 4; further
data are collected in Tables 6 and 7 ꢀsignals corresponding to aromatic moieties of
protecting groups are omitted). The con®guration at C-1 within a pair of
diastereomers formed by MSꢀ2,rO) can be deduced from the set of couplings
observed with the nuclei F, H-1, and H-2 [11], but this was not done with the
products obtained here. They are designated simply as isomers `a' or `b'; this holds
also for the pair of diastereoisomers in compound 59.
Experimental
General
NMR spectra were recorded at 300.13 or 200 MHz ꢀ1H), 75.47 or 50.29 MHz ꢀ13C), and 282.4 MHz
ꢀ19F) using a Bruker MSL 300 and a Varian Gemini 200 apparatus, respectively, except for the
elucidation of 59 where a Varian Inova 500 spectrometer was employed. As reference standards,
tetramethylsilane ꢀ1H and 13C NMR) and trichloro¯uoromethane ꢀ19F NMR) were used. TLC was
performed on silica gel 60 F254 precoated aluminum plates ꢀMerck 5554) with detection by charring
after spraying with vanillin=H2SO4 ꢀ1%). For column chromatography, silica gel 60, 230±400 mesh
ꢀMerck 9385), was employed.
General procedure for the DAST-reaction
Analytical Scale: To a cold ꢀ0ꢀC) solution of 0.1 mmol educt in 1 cm3 absolute CH2Cl2, 0.04±
0.05 cm3 DAST ꢀ0.30±0.38 mmol) were added under stirring. After 10 min the cooling bath was
removed, and the mixture was stirred at room temperature for 5 h under monitoring by TLC
ꢀgenerally, the reaction products are faster moving than the educt). For the 19F NMR measurements,
0.4 cm3 of the reaction mixture were transferred into the NMR tube and diluted with CDCl3.
Preparative Scale: The reaction conditions were the same as used in the analytical scale. The
amount of educt, solvent, and reagent was ten- to ®fteen-fold. The reaction time was extended to
15±24 h. Work-up started with dilution of the reaction mixture with CH2Cl2 and quenching of the
excess reagent by addition of an excess of MeOH. After 15 to 20 min the mixture was then extracted
with H2O, followed by aqueous NaHCO3 and again H2O. After drying with Na2SO4 the solvent was
evaporated, and the residue was chromatographically puri®ed on silica gel.
Note Added in Proof
After having submitted the manuscript we became aware of a recent paper dealing with the DAST
reaction of glycosides and thioglycosides of 3-deoxy-3-C-methyl-3-nitro-D=L-gluco- as well as
-mannopyranoses [29]. These educt structures, in the same way as ours, are subject to either ring
contraction ꢀMSꢀ2,rO)) or aglycon migration ꢀASꢀ2,NG-1)) and show, as is to be expected, a higher
degree of reactivity in displacement reactions at C-2. As the presented generalizations concerning
the diacritic structural parameters in the choice of the side reaction were in contrast to those we had
deduced from our ®ndings, a thorough inspection of the reported 1H and 13C NMR data was carried
out in order to re-examine the elucidation of product structures. From the value of the geminal 19F,

Fluorination of Glucopyranosides with DAST
447
1H couplings ꢀ2JF,H) and other diacritical data ꢀe.g. chemical shifts of H-2 and C-2, respectively) it
has to be concluded that the structure appointments are wrong in 8 cases. According to our
interpretation of the data, the methyl ꢀ-L-manno derivative as well as all thioglycosides ꢀꢀ- and
ꢁ-anomers from the D=L-gluco series) were subject to ASꢀ2,NG-1), whereas all O-glycosides with
ꢀ- or ꢁ-D=L-gluco con®guration, including those containing a 4,6-O-benzylidene protection, gave
MSꢀ2,rO) only. This is in full agreement with parameters we have deduced herein from our re-
sults, except that in the ꢀmore reactive) 3-deoxy-3-C-methyl-3-nitro-glucopyranose case, a 4,6-O-
benzylidene protection does no more cause prevention of the ring contractive MSꢀ2,rO)-reaction.
Acknowledgements
We appreciate ®nancial support by the Fonds zur Forderungder wissenschaftlichen Forschung ,
Vienna ꢀP-11021 OECH) and thank Chemprosa, Lannach ꢀAustria) for the gift of educts for this
investigation. Student coworkers in the synthesis of educts as well as their treatment with DAST have
been: R. Peinsipp, J. Wolfgang, G. Koller, B. J. Paul, F. Burghart, C. Gruber, W. Haas, M. Grininger,
R. Harrer, W. Kroutil, S. Leitgeb, M. Waldhuber, D. Kober, T. Sovic, and J. Steinreiber. They are all
thanked for their valuable help in these laborious studies.
References
[1] For an overview see: Liebmann JF, Greenberg A, Dolbier WR ꢀeds) ꢀ1988) Fluorine-Containing
Molecules, Structure, Reactivity, Synthesis and Applications. VCH, Weinheim
[2] Detailed data are collected in: Tsuchiya T ꢀ1990) Adv Carbohydr Chem Biochem 48: 91
[3] Dax K, Albert M, Ortner J, Paul BJ ꢀ2000) Carbohydr Res 327: 47
[4] Dax K, Albert M, Ortner J, Paul BJ ꢀ1999) Curr Org Chem 3: 287
[5] Dax K, Albert M ꢀ2001) In: Stutz AE ꢀed) Glycoscience: Epimerisation, Isomerisation and
Rearrangement Reactions in Carbohydrates. Springer, Berlin, p 193
[6] Kovac P ꢀ1986) Carbohydr Res 153: 168
[7] Haradahira T, Maeda M, Omae H, Yano Y, Kojima M ꢀ1984) Chem Pharm Bull 32: 4758
[8] Haradahira T, Maeda M, Kai Y, Omae H, Kojima M ꢀ1985) Chem Pharm Bull 33: 165
[9] Kovac P, Yeh HJC, Jung GL, Glaudemans CPJ ꢀ1986) J Carbohydr Chem 5: 497
[10] Castillon S, Dessinges A, Faghih R, Lukacs G, Olesker A, Thang TT ꢀ1985) J Org Chem 50:
4913
[11] Baer H, Hernandez Mateo F, Siemsen L ꢀ1989) Carbohydr Res 187: 67
[12] Llewellyn JW, Williams JM ꢀ1973) J Chem Soc Perkin Trans I, 1997
[13] Erbing C, Lindberg B, Svensson S ꢀ1973) Acta Chem Scand 27: 3699
[14] Ivanova IA, Nikolaev AV ꢀ1998) J Chem Soc Perkin Trans I, 3093
[15] a) El Nemr A, Tsuchiya T ꢀ2001) Carbohydr Res 330: 205; b) El Nemr A, Tsuchiya T ꢀ1997)
Carbohydr Res 303: 267; c) El Nemr A, Tsuchiya T ꢀ1997) Carbohydr Res 301: 77; d)
El Nemr A, Tsuchiya T, Kobayashi Y ꢀ1996) Carbohydr Res 293: 31; e) El Nemr A, Tsuchiya T
ꢀ1995) Tetrahedron Lett 36: 7665
[16] Nicolaou KC, Ladduwahetty T, Randall JL, Chucholowski A ꢀ1986) J Am Chem Soc 108: 2466
[17] El Sayed Ahmed FM, David S, Vatele J-M ꢀ1986) Carbohydr Res 155: 19
[18] Fleet GWJ, Seymour LC ꢀ1987) Tetrahedron Lett 28: 3015
[19] a) Charette AB, Cote B, Marcoux J-F ꢀ1991) J Am Chem Soc 113: 8166; b) Charette AB, Cote B
ꢀ1993) J Org Chem 58: 933
[20] Ogawa T, Takahashi Y ꢀ1983) J Carbohydr Chem 2: 461
[21] Street IP, Withers SG ꢀ1986) Can J Chem 64: 1400
[22] a) Bliard C, Herczegh P, Olesker A, Lukacs G ꢀ1989) J Carbohydr Chem 8: 103; b) Bliard C,
Cabrera Escribano F, Lukacs G, Olesker A, Sarda P ꢀ1987) J Chem Soc Chem Commun: 368

448
K. Dax et al.
[23] Akiya S, Osawa Tꢀ1959) Chem Pharm Bull 7: 277; see also Irvine JC, Hynd OA ꢀ1914) J Chem
Soc 698
[24] Chan W-P, Gross PH ꢀ1980) J Org Chem 45: 1369
[25] a) Robins MJ, Wnuk SF, Mullah KB, Dalley NK ꢀ1994) J Org Chem 59: 544; b) Fuchigami T,
Konno A, Nakagawa K, Shimojo M ꢀ1994) J Org Chem 59: 5938; c) Takeuchi Y, Asahina M,
Hori K, Koizumi Tꢀ1988) J Chem Soc Perkin Trans I, 1149
[26] Montchamp J-L, Tian F, Hart ME, Frost JW ꢀ1996) J Org Chem 61: 3897
[27] Aghmiz ML, Diaz Y, Jana GH, Matheu MI, Echarri R, Castillon S, Jimeno ML ꢀ2001)
Tetrahedron 57: 6733
[28] Baillargeon DJ, Reddy GS ꢀ1986) Carbohydr Res 154: 275
[29] Borrachero P, Cabrera-Escribano F, Carmona AT, Gomez-Guillen M ꢀ2000) Tetrahedron Asymm
11: 2927
Received November 26, 2001. Accepted November 28, 2001