E versus Z geometry in β-d-arabino-hexopyranosidulose oximes

Article abstract of DOI:10.1016/j.carres.2009.08.007

Koenigs-Knorr-type glycosidations of peracylated 2Z-benzoyloxyimino-glycopyranosyl bromides invariably proceed with retention of the Z-geometry. Accordingly, the many β-d-hexosidulose oximes in literature which were prepared in this way and for which the

Full text of DOI:10.1016/j.carres.2009.08.007

Carbohydrate Research 344 (2009) 2127–2136
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E versus Z geometry in b-D-arabino-hexopyranosidulose oximes q
*
Matthias Lergenmüller, Ulrich Kläres, Frieder W. Lichtenthaler
Clemes-Schöpf-Institut für Organische Chemie und Biochemie, Technische Universität Darmstadt, Petersenstraße 22, D-64287 Darmstadt, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 28 May 2009
Received in revised form 31 July 2009
Accepted 1 August 2009
Available online 12 August 2009
Koenigs–Knorr-type glycosidations of peracylated 2Z-benzoyloxyimino-glycopyranosyl bromides invari-
ably proceed with retention of the Z-geometry. Accordingly, the many b-
D-hexosidulose oximes in liter-
ature which were prepared in this way and for which the oxime geometry has not been addressed
explicitly, are the Z-oximes throughout. By contrast, oximation of b-D-hexopyranosid-2-uloses leads to
mixtures of E and Z oximes readily separable and structurally verifiable by 1H and 13C NMR. Configura-
tional assignments rested on comparative evaluation of NMR data of E and Z isomers, and, most notably
Keywords:
on an X-ray structural analysis of the pivaloylated isopropyl 2E-benzoyloxyimino-2-deoxy-b-
D-arabino-
Hexosidulose oximes
E versus Z geometry
hexopyranoside revealing the unusual 1S5 ꢀ 1,4B conformation for the pyranoid ring.
1S5
ꢀ
1,4B conformation
Ó 2009 Elsevier Ltd. All rights reserved.
OR2
OR2
O
1. Introduction
O
R2O
Within the last two decades, oximes of
siduloses have figured prominently as key intermediates for the
straightforward preparation—by reduction and N-acetylation—of
D
-arabino-hexopyrano-
R2O
R2O
R2O
OR1
OR
N
OR
OR1
N
oligosaccharides with
a-D-GlcNAc residues from a
-anomers2–4
I
II
and, more importantly, with b-
D-ManNAc units from the respective
β-D-arabino
α-D-arabino
b-counterparts (Scheme 1).5
For
a- -hexopyranosidulose oximes of type I, ample evidence has
D
1. Red.
2. Ac2O
1. Red.
2. Ac2O
accumulated that invariably the Z geometry is adopted with the N–
OH or N–O-acyl group pointing toward the anomeric center. This
entails the N-OR group to be essentially coplanar to the equatorial
anomeric hydrogen causing a distinct deshielding and, hence, up-
field shift of its 1H NMR signal by up to 0.6 ppm as compared to
the parent 2-ketose—a fact that has provided convenient configu-
rational proof.6 Similar conclusions may be derived from 13C chem-
ical shifts of the carbons vicinal to the carbonyl resp.
oximinocarbonyl group, as the carbon on the same side as the N–
OH exhibits a significantly larger upfield shift than the other.1 Full
conformational details have been provided by two X-ray struc-
tures, that is, I with OEt7 and pyrazol8 (R2 = Ac) as anomeric sub-
stituents, disclosing the adoption of a 4C1 conformation slightly
flattened around C-2.
OR2
R2O
R2O
NHAc
O
O
R2O
R2O
R2O
OR1
AcHN
OR1
α-D-GlcNAc
R = H, acyl; R1 = alkyl, glycosyl; R2= Ac, Bz, Bn
β-D-ManNAc
Scheme 1. The oximino-ulosyl donor approach for the generation of
and b- -ManNAc units.
a-D-GlcNAc
D
The same Z-oxime-OH geometries are observed for various 4-
epimeric
an anomeric substituent (H instead of OR1), that is, the oximes of
1,5-anhydro-ketoses of -tagato-, -rhamnulo- and
-fructo-3a,10,11
-xylulo configuration.1
a-D
-lyxo analogs of I4b,6c,9 as well as for analogs lacking
In the case of b-configurated hexopyranosidulose oximes of type
II, the N–OH or N–OR group is—in the 4C1 conformation of the pyr-
anoid ring—coplanar either to the anomeric substituent (Z geome-
try) or to the equally equatorial C-3 acyloxy group (E-oxime).
Accordingly, one would expect the formation of either oxime or
mixtures thereof. Indeed, there are two cases in the literature12
where mixtures of E/Z oximes have been obtained upon oximation
D
D
L
D
q
Part 44 of the series, sugar-derived building blocks; for Part 43, see Ref. 1.
* Corresponding author. Tel.: +49 6151 162376.
E-mail address: lichtenthaler@chemie.tu-darmstadt.de (F.W. Lichtenthaler).
0008-6215/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2009.08.007

2128
M. Lergenmüller et al. / Carbohydrate Research 344 (2009) 2127–2136
OAc
O
H4
OAc
O
AcO
OAc
H4
X
O
N
X
AcO
AcO
H3
AcO
X
OH
AcO
AcO
N
H3
4C1
OH
N
OH
3,0B
0S2
X = N3, NHAc
Scheme 2. Distortion of pyranoid ring conformations in two b-
D
-arabino-hexosidulose E-oximes as derived from X-ray data.15,16
of b-
D-arabino-hexosiduloses yet they were neither separated nor
2. Results and discussion
the products were sufficiently characterized. On the other
hand, the large number of b- -arabino-hexosidulose benzoyloxi-
D
2.1. Oximation of b-D-hexopyranosiduloses: E/Z mixtures
mes of type II, prepared via the oximino-ulosyl donor ap-
proach,3,5,10,11,13,14 has, surprisingly, not been scrutinized as to
their N–OBz geometry. Conformationally, the steric strain in the
4C1 chair form of these Z benzoyloximes caused by the near coplan-
arity of N–OBz with either the anomeric (Z form) or the C-3 substi-
tuent (E isomer) is evaded by distortion of the pyranoid ring, as
indicated by comparatively small J3,4 and J4,5 couplings. Obviously,
the distortion operates toward adoption of the 0S2 skew or twist/
boat form (Scheme 2), evidenced by two X-ray structures, with
As b-
dation of 2-OH-free b-
alcoholysis of
-ulosyl bromides 2?3,5 a standard procedure for
generating the respective oximes is their direct oximation by expo-
sure to hydroxylamine. Despite several examples in the litera-
ture,12,18 the oximes obtained were—except for a ribose- and
galactose-derived case19—not characterized as such, but directly
subjected to reduction and N-acetylation toward the actual targets,
D
-hexopyranosiduloses are readily prepared either by oxi-
D
-glucosides 1?317 or by Ag2CO3-promoted
a
N3 and NHAc16 as anomeric substituents.
15
that is, b-
D-ManNAc units in oligosaccharides.
In more closely addressing the E versus Z geometry in b-D-ara-
As demonstrated here with the oximation of isopropyl b-
D
-ara-
bino-hexosidulose oximes, which appears to depend on their mode
of generation, we here report the preparation, interconversion and
unequivocal configurational assignments of five E and Z isomeric
pairs, and provide evidence for the respective conformational dis-
tortions in their pyranoid rings.
bino-hexopyranosiduloses carrying benzoyl (3a), pivaloyl (3b), and
benzyl blocking groups (3c) (Scheme 3), oximation under standard
conditions invariably led to E/Z mixtures of the respective oximes,
their proportions varying with the size of the vicinal 3-O-substitu-
ent: 2:1 in favor of the E isomer in the benzoyl derivatives 4a, and
5:1 in the pivaloylated products 4b. In the case of the more slender
benzyl groups, that is, 3c?4c, the E/Z-proportion of the oximes is
reversed to 1:2.
As shown by the O-benzoylation of the oxime hydroxyls
(benzoyl chloride/pyridine, rt), these oximes are interconvertible,
at least to equilibrium mixtures: the 5:1 E/Z mixture of pivaloy-
lated oximes 4b—or either of the pure E-4b and Z-4b—changes
to 8:1 (1H NMR), allowing the isolation of pure E-5b by
fractional crystallization. All other E/Z mixtures were separated
by chromatography and the individual geometrical isomers were
characterized by their polarometric, 1H and 13C NMR data (cf.
Table 1).
In the disaccharide-uloside 6, oximation similarly led to E/Z
oxime mixtures in favor of the E-isomer (5:1 ratio), which on ben-
zoylation changes to 20:1, thus greatly facilitating the isolation of
8E (Scheme 4). Its physical data clearly distinguished it from its Z
isomer 8Z, which had already been prepared independently, that
is, by Ag2CO3-promoted alcoholysis of benzoyloximino-hexosyl
bromide 13a (vide infra) with diacetone-galactose.13
OR
OR
O
O
RO
RO
RO
RO
OR'
O
HO
Br
1
2
Ag2CO3
R'OH
Oxid.
OR
O
RO
RO
OR'
O
3
NH2OH
A further indication for the E ꢀ Z interconversion of the oxi-
mes came from the surprising finding that the benzoximes 5,
yet not the oximes 4 as such, show mutarotation in CHCl3 (cf. Ta-
ble 1) whilst rotational values are constant in dichloromethane. In
the pivaloylated cases, this rotational change, apparently induced
by the minime trace of acid contained in the CHCl3, is distinct:
(R' = iPrOH)
OR
N
OR
O
O
RO
RO
RO
RO
+
O
O
XO
N
OX
½
a 2D0
ꢀ
values (from ꢁ59.5° to +56.8° within 24 h for the E-ben-
4E X = H
5E X = Bz
4Z X = H
5Z X = Bz
zoyloxime 5b versus +85.5° to +60.5° for the Z-isomer), indicating
an equilibration from each side to an approximate 1:8 E/Z
mixture, hence, the Z-isomer being the thermodynamically more
stable.
BzCl
BzCl
a-series: R = benzoyl; b-series: R = pivaloyl; c-series: R = benzyl;
R’ = alkyl, glycosyl
Configurational assignments. The proof of E and Z geometry for
the oximes 4, 5, 7, and 8 is arduous in so far, as either substituent
vicinal to the oximino carbon is in an equatorial disposition, hence
Scheme 3. Generation and oximation of b-D-arabino-hexopyranosiduloses.

M. Lergenmüller et al. / Carbohydrate Research 344 (2009) 2127–2136
2129
Table 1
Selected 1H and 13C NMR data in CDCl3 and ½aꢀ values for isopropyl b-D-arabino-hexopyranosiduloses and their E and Z oximino analogs
D
Compound
H-1
H-3
J3,4
J4,5
C-1
C-3
½ ꢀ (CHCl3)
a 2D0
OR
3a
3b
3c
R = Bz13
R = Piv
5.22
5.05
4.85
5.98
5.49
4.22
10.0
10.1
7.9
8.0
9.1
9.2
78.6
98.4
98.0
77.1
76.4
85.9
ꢁ52.3
ꢁ22.2
ꢁ49.0
O
R = Bn20
RO
RO
OiPr
OiPr
O
OR
O
R
R0
H
H
H
Bz
Bz
Bz
4a
4b
4c
5a
5b
5c
Bz
Piv
Bn
Bz
Piv
Bn
5.40
5.26
5.26
5.70
5.56
5.54
6.60
6.08
5.01
6.73
6.31
5.06
6.7
6.7
4.4
6.9
6.9
4.9
7.2
7.7
5.2
7.3
8.2
5.4
95.0
94.1
95.2
95.0
94.7
94.9
63.6
69.5
75.3
64.6
64.2
71.3
ꢁ74.1
ꢁ18.5
RO
RO
ꢁ35.1
ꢁ7.9?ꢁ21.2 (1h)
+85.3?+60.5 (24h)
ꢁ9.1
N
R'O
E
4b
4a
4c
5a
5b
5c
Piv
Bz
Bn
Bz
Piv
Bn
H
H
H
Bz
Bz
Bz
6.04
5.99
5.88
6.19
6.04
6.00
6.01
5.42
4.09
6.20
5.72
4.40
5.7
4.7
2.4
5.0
5.2
2.8
5.5
4.5
89.6
87.9
90.5
90.4
89.7
90.8
68.7
67.1
75.3
68.7
67.7
74.9
ꢁ73.3
ꢁ13.5
ꢁ35.1
OR
O
Oi Pr
OR'
RO
RO
4.8
5.0
5.1
ꢁ60.7?ꢁ 21.2 (1h)
ꢁ59.9?+56.8 (24h)
ꢁ27.5
N
Z
6
X = O
X = HO–N
5.40
5.36
5.67
6.02
6.09
5.99
6.58
6.74
6.00
6.26
10.0
10.1
8.6
8.3
5.6
5.3
99.3
97.2
97.3
91.7
93.2
76.7
63.9
65.3
68.7
68.7
OBz
O
7E
8E
7Z
8Z
7.1
7.1
6.0
4.3
X = BzO–N
X = N–OH
OiP2Gal
BzO
BzO
X = N–OBz14a
X
OBz
O
proton and H-1 or H-3, that is, irradiation of H-1 in Z-4b at
5.99 ppm caused inversion not only of the H-3 and H-5 signals,
but of the N–OH signal at 8.85 ppm as well. In turn, irradiation
of H-3 at 5.42 ppm had no effect on the oxime-OH. In the E-4b
case, the correlations between H-1 resp. H-3 and the N–OH were
reverse, as expected.
O
O
BzO
O
O
BzO
O
O
X
6 X = O
7 X =
8 X =
In addition, we succeeded in obtaining a single crystal of the
pivaloylated E-benzoyloxime E-5b suitable for an X-ray diffraction
analysis (Fig. 1). As clearly inferable from the dihedral angles listed
out in Table 2, the pyranoid ring adopts a conformation lying be-
tween a 1,4B boat and the 1S5 form, whilst the N–OBz group points
away from the anomeric center, the respective torsion angle C1–
C2–N2–O21 indicating the N–O bond being in antiparallel arrange-
ment (–178.0°) to C1–C2. A more lucid substantiation of the
1,4B ꢀ 1S5 conformation of E-5b is provided by the Cremer–Pople
ring puckering parameters21 (Table 3): the puckering angles /=
255°, h= 88.3°, and the amplitude Q = 0.772 Å show the excepted
angles /= 270° and h= 90° for 1,4B and /= 240° and h= 90° for 1S5,
respectively.22 Atoms forming the least-squares planes of both
conformations—C-2, C-3, C-5, and O-1 for the 1,4B boat and C-2,
C-3, C-4, and O-1 for the twisted 1S5 form—diverge approximately
0.10 Å from the best-fit ring plane (Table 3 and Fig. 2). The identical
deviation of atoms defining these planes emphasizes on the real
conformation lying between the extremes, from which the 1,4B is
defined by ring atoms C-1 and C-4 positioned 0.62 Å and 0.67 Å
above the plane, whereas the 1S5 conformation is described by
one atom lying above the plane (C-1: 0.75 Å) and one lying below
(C-5: 0.65 Å).
NH2OH
BzCl
N
N
OH
E/Z 5:1
E/Z 20:1
OBz
Scheme 4. E- resp. Z-oximes of a D-arabino-hexosulosyl-b(1?6)-D-galactose.
is sterically interfering in either arrangement with the essentially
coplanar oxime–OH or –OBz groups. This steric congestion is re-
leased by distortion of the pyranoid ring, as evidenced by the com-
paratively small J3,4 and J4,5 coupling constants, sometimes even as
low as J3,4 = 2.8 (Z-5c) and J4,5 = 4.5 Hz (Z-4b) (cf. Table 1). By con-
trast, the parent ulosides 3 and 6, exhibit J3,4 and J4,5 couplings in
the 9–10 Hz range, clearly proving the adoption of the 4C1 confor-
mation throughout. Thus—unlike their
a-anomeric counterparts,
where the downfield shift of the equatorial H-1 by the Z N–OR
group relative to the parent uloside is a clear indicator of Z
geometry1,6—the b-anomeric uloside/uloside oxime counterparts
provide no unambiguous clues on this basis.
Aside an independent, essentially stereospecific synthesis of
the Z-benzoyloximes of 5a–5c, 8, and 10 (vide infra: 2.2),
unequivocal proof for the oxime geometries was derived from
the following pieces of evidence: (i) All Z oximes listed out in
Table 1 show their anomeric hydrogens at lower field (5.9–
6.2 ppm) than their E isomers (5.4–5.7 ppm), obviously reflecting
the deshielding through the Z-NOH; for H-3, not being affected
by a Z-oriented oxime hydroxyl, the situation is reverse, its
chemical shift being at higher field up to 1 ppm for the Z isomers
relative to their E analogs. (ii) The NOESY spectra of E-4b and
Z-4b showed the expected correlations between the N–OH
On the basis of these results it may be concluded that the clo-
sely related E isomeric benzoximes E-5a, E-5c, and E-8 will simi-
larly adopt conformations approximating the 1,4B ꢀ 1S5 forms—in
the solid state. In solution, conformations appear to be different,
since the dihedral angles H-3 to H-4 and H-4 to H-5 are 158.6°
and 173.9°, respectively (Table 2), whilst the J3,4 and J4,5 couplings
with 5.2 and 5.0 Hz, are comparatively too small.

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M. Lergenmüller et al. / Carbohydrate Research 344 (2009) 2127–2136
H3C
O
CH3
OPiv
PivO
PivO
O
N
BzO
E - 5b
Figure 1. Perspective view of the X-ray structure of isopropyl 3,4,6-tri-O-pivaloyl-2E-benzoyloxyimino-2-deoxy-b-D-arabino-hexopyranoside E-5b and numbering system. To
facilitate visualization of the 1,4BM1S5 conformation of the pyranoid ring, a second view is given (right) in which pivaloyl groups and i-propyl substituent are omitted for
clarity.
Table 2
Torsion angles in E-5b
2.2. Z-Oximes of b-D-arabino-hexopyranosiduloses
Whilst the alcoholysis of 2-nitrosohexosyl chlorides invariably
led to
-hexosidulose oximes,6 the preparatively more important
b-counterparts—they constitute key intermediates toward the
straightforward assembly of b- -ManNAc containing oligosaccha-
rides5—are either prepared by oximation of b-
-hexosiduloses as
Pyranoid ring
(°)
Substituents
(°)
a
C1–C2–C3–C4
C2–C3–C4–C5
C3–C4–C5–O1
C4–C5–O1–C1
C5–O1–C1–C2
O1–C1–C2–C3
+15.2
+45.0
–66.9
+18.7
+41.3
ꢁ60.2
C1–C2–N2–O21
O11–C1–C2–N2
N2–C2–C3–O31
N2–C2–C3–C4
H3–C3–C4–H4
H4–C4–C5–H5
ꢁ178.8
ꢁ111.0
+66.0
ꢁ173.7
+158.6
+173.9
D
D
discussed above (Section 2.1.) or by the Koenigs–Knorr type glycos-
idation of 2-benzoyloximinoglycosyl bromides (Scheme 5, 13?5).
The generation of these oximino-ulosyl donors is preparatively
most straightforward, as the readily large-scale accessible 2-
hydroxyglycal esters 10 smoothly undergo hydroxylaminolysis of
Table 3
Deviations in E-5b from the least-squares best-fit plane in Å formed by four atoms
and ring puckering parameters
their enol ester group,5 and the resulting 1,5-anhydro-
D-fructose
oximes 11—after O-benzoylation (?12)—are readily refunctional-
ized at the proanomeric center by photobromination 12?13.10
In the oximes 11–13, the N–OH or N–OBz group is always ori-
ented toward the anomeric or proanomeric center as indicated in
the formulae, a fact readily rationalized on the basis that the copla-
nar equatorial H-1 exerts considerably less steric congestion than
the equally equatorial 3-OBz. Unequivocal proof for the Z geometry
Atom
1,4B
1S5
Puckering parameters
C-1
C-2
C-3
C-4
C-5
O-1
0.62
0.75
/ = 255.1°
h = 88.3°
ꢁ0.10a
0.10a
ꢁ0.10a
0.10a
0.10a
0.67
Q = 0.722 Å
ꢁ0.10a
ꢁ0.65
0.10a
ꢁ0.10a
of benzoyloximinohexosyl bromides 13 as well as the respective a-
a
Atoms defining a plane.
Figure 2. Graphic representation of the molecular geometry of E-5b lying between the 1,4B boat and the twisted 1S5 conformation. The deviations of the ring atoms from the
calculated best planes (indicated by dotting) are given in Å. Substituents at C-3 to C-5 are omitted for clarity.

M. Lergenmüller et al. / Carbohydrate Research 344 (2009) 2127–2136
2131
leads to E/Z mixtures of the respective oximes, their proportions
varying with the size of the vicinal anomeric and 3-O-substituent.
Their separation is readily accomplished providing the E and Z iso-
mers in pure form thereby substantially facilitating structural and
configurational assignments by NMR, notably NOESY experiments,
and, in one case, by an X-ray structure. By contrast, preparation of
OR
OR
O
O
NH2OH
RO
RO
RO
RO
OR'
N
OR
11 R' = H
12 R' = Bz
10
b-D-arabino-hexosidulose oximes via Koenigs–Knorr glycosidation
OR
of Z-benzoyloximino-hexosyl bromides uniformly leads to pure
Z-oximes, that is, without touching the steric integrity of the oxime
moiety.
NBS / hν
O
RO
RO
Due to the coplanarity in the 4C1 form of the N–OH or N–OBz
groups to either the anomeric (Z isomers) or the 3-O substituent
(E counterparts), both evade this steric congestion by distortion
of the pyranoid ring, as evidenced by J3,4 and J4,5 values much too
small for diaxial arrangement of the respective hydrogens. Based
on the X-ray structural data of the E-benzoyloxime described here
and two Z-oximes from the literature,15,16 these distortions can be,
at least for the solid state, be specified: adoption of the 1S5 ꢀ 1,4B
conformation in the case of E-oximes versus the 0S2 ꢀ 3,0B forms
for their Z isomers (Fig. 3), both being closely interrelated via the
B2,5 boat form on the pseudorotational boat/skew cycle25 of the
pyranoid ring.
OBz
N
Br
13
Ag2CO3
iPrOH
Ag triflate
iPrOH
OR
OR
O
O
RO
RO
RO
RO
O
OBz
N
N
OBz
O
5
14
4. Experimental
4.1. General
a-series: R = benzoyl; b-series: R = pivaloyl; c-series: R = benzyl;
Scheme 5. Generation of 2Z-benzoyloxyimino-hexopyranosyl bromides 13 and
means for their selective a-(?14) and b-glycosidation (?5).
Melting points were determined with a Bock hot-stage micro-
scope and are uncorrected. Optical rotations were measured at
20 °C with a Perkin–Elmer 241 polarimeter using a cell of 1 dm
path length. 1H and 13H NMR spectra were recorded on Bruker
ARX 300 and Avance 500 instruments. Mass spectra were acquired
on a Varian MAT 311 spectrometer, microanalyses on a Perkin–El-
mer 240 elemental analyzer. Analytical thin layer chromatography
(TLC) was performed on Kieselgel 60 F254 plastic sheets (Merck,
Darmstadt) with detection by UV light or by spraying with 50% sul-
hexosidulose oximes 14, prepared by silver triflate-promoted
alcoholysis of 13, was convincingly derived from the downfield
shift of the equatorial anomeric hydrogen induced by the coplanar
N–OBz group as compared to their respective 2-oxo analogs. The
data compiled in Table 4, widely scattered in the literature, provide
ample evidence thereof, the shift of the equatorial anomeric hydro-
gen to lower field amounting to 0.6–1.2 ppm.
That the three b-configurated hexosidulose oximes 5 with
R = Bz, Piv and Bn (cf. Scheme 3), prepared by Koenigs–Knorr gly-
cosidation of the respective Z-benzoyloximinohexosyl bromide
13 with i-propanol, also have the Z configuration was already indi-
cated by the distinctly uniform course of these glycosidations gen-
erating single products isolable in high yields. Unambiguous proof
followed from their identity with the Z forms of 5a, 5b, and 5c
independently prepared by oximation of the glycosiduloses and
subsequent benzoylation (vide supra: 2.1, Scheme 2).
OR
O
OR
RO
OR'
O
N
OR'
RO
RO
RO
OR''
N
OR''
3,0
0
S
2
Z
B
On the basis of these results, an important conclusion as to the
steric course of the oxime reactions depicted in Scheme 5 can be
drawn: Neither the conditions of the photobromination 12?13
RO
RO
RO
O
(NBS in CCl4, hm, 15 min reflux) nor those for the a-glycosidation
OR'
of the benzoyloximino-ulosyl bromides 13?14 (Ag-triflate/
dioxane, s-collidine, rt), or the Koenigs–Knorr alcoholysis 13?5
(stirring with Ag2CO3/ROH in CH2Cl2, rt) affect in any way the Z
geometry in the benzoyloximino groups.
N
OR''
This inference has important bearing on the large number of
b-D-arabino-hexosidulose benzoyloximes of type II (Scheme 1),
E
OR'
OR'
prepared via the oximino-ulosyl donor approach,3,5,10,11,13,14 whose
N–OBz geometries have, surprisingly, not been scrutinized
explicitly as of now: As the essentially b-specific Koenigs–Knorr
glycosidation of the Z-benzoyloximino-ulosyl bromides proceeds with
retention of configuration, they invariably have the Z geometry
throughout.
RO
RO
RO
RO
O
O
RO
N
OR
R''O
N
R''O
1,4
B
1
S
5
3. Conclusion
R = Bz, Piv, Bn; R' = alkyl, glycosyl; R'' = H, Bz
The above experimental results demonstrate, that exposure of
Figure 3. Pyranoid ring distortions in E and Z isomers of b-D-arabino-hexosidulose
b-D
-arabino-hexopyranosiduloses to hydroxylamine invariably
oximes.

2132
M. Lergenmüller et al. / Carbohydrate Research 344 (2009) 2127–2136
Table 4
Proof of Z geometry of 2-ulopyranoside oximes on the basis of the deshielding, hence downfield shift, of the equatorial anomeric hydrogen by the coplanar oxime-OH or OAcyl
group as compared to the parent ulosides
Compda
H-1e
H-3
J3,4
J4,5
Downfield shift of H-1e (ppm)
Ref.
OBz
O
X = O
X = N–OH
X = N–OBz
4.57
5.17
5.35
6.19
6.02
6.30
9.8
7.2
6.5
9.8
8.1
6.9
—
0.60
0.78
11
11
10
BzO
BzO
X
OBz
R
X
O
—
Bz
Bz
Piv
Piv
6.52
ꢄ7.5b
6.40
6.54
6.70
6.00
6.21
10.4
10.0
10.4
10.2
10.4
10.0
10.4
10.2
13
10
13
c
O
N–OBz
O
N–OBz
ꢄ1.0
—
1.01
BzO
BzO
7.41
X
Br
OAc
O
X = O
X = N–OH
4.94
6.14
5.70
5.87
10.0
9.5
10.0
9.5
—
1.20
6c
6a
AcO
AcO
X
OiPr
COOMe
X = O
X = N–OH
5.21
6.18
6.20
6.26
10.3
9.7
10.1
9.8
—
0.97
23
23
O
BzO
BzO
X
OCx
OR
R
X
Bz
Ac
O
5.14
6.02
6.17
5.76
10.2
9.7
10.2
9.9
—
0.88
24
4b
O
RO
RO
N–OAc
X
OCx
a
b
c
Cx = cyclohexyl.
Signal obscured by aromatic protons.
This paper.
furic acid and charring at 140 °C for 5 min. Column chromatogra-
phy was performed on Silica Gel 60 (Merck, 63–200 ppm) using
the specified eluents.
(120 mL), washing with 2 M HCl (2 ꢃ 40 mL), satd NaHCO3
(20 mL), water (20 mL), drying (Na2SO4), and removal of the sol-
vent in vacuo afforded a 2:1 mixture (1H NMR) of E and Z-isomers
(5.20 g, 95%) as a hard foam. Separation was effected by elution
from a silica gel column with 20:1 toluene/EtOAc.
4.2. Isopropyl 3,4,6-tri-O-pivaloyl-b-D-arabino-hexopyranosid-
2-ulose 3b (R0 = iPr)
4.3.1. Z-Oxime Z-4a
A mixture of iPrOH (185 L, 1.4 mmol), silver carbonate (330 mg,
1.2 mmol) and molecular sieve (3 Å, 500 mg) in dry CH2Cl2 (15 mL)
was stirred at room temperature for 30 min, followed by the addi-
tion of ulosyl bromide 2b13 (600 mg, 1.2 mmol). After stirring for
another h the suspension was filtered, and the solvent was re-
moved under reduced pressure. Trituration of the resulting syrup
with Et2O gave 3b (540 mg, 95%) in crystalline form; mp 121–
Concentration of the first fraction (Rf 0.10 in 20:1 toluene/
EtOAc) yielded Z-4a (1.43 g, 26%) as a colorless solid; ½a D20
ꢁ73.3
ꢀ
(c 1.4, CHCl3); –84.6 (c 1.2, CH2Cl2). 1H NMR (300 MHz, CDCl3):
1.17, 1.27 (2d, 6H, C(CH3)2), 4.14 (qq, 1H, CHMe2), 4.45 (dt, 1H,
H-5), 4.84 (2H-d, 6-H2), 5.86 (dd, 1H, H-4), 6.01 (d, 1H, H-3), 6.04
(s, 1H, H-1), 7.30–8.10 (m, 15H, 3C6H5), 8.85 (s, 1H, NOH),
J3,4 = 5.7, J4,5 = 5.5, J5,6 = 6.6, JCH,CH3 = 6.1 Hz; 13C NMR (75.5 MHz,
CDCl3): 21.4, 23.0 (C(CH3)2), 65.3 (C-6), 68.7 (C-3), 69.3 (C-4),
71.3 (CMe2), 72.7 (C-5), 89.6 (C-1), 128.3–133.5 (3C6H5), 149.6
(C-2), 165.1, 165.3, 166.2 (3COC6H5), JC-1,1-H 171.3 Hz. Anal. Calcd
for C30H29NO9 (547.56): C, 65.81; H, 5.34; N, 2.56. Found: C,
65.68; H, 5.32; N, 2.49.
128 °C; Rf = 0.30 (4:1 CCl4/EtOAc); ½a D20
ꢀ
ꢁ22.2 (c 1, CHCl3). 1H
NMR (300 MHz, CDCl3): 1.19, 1.22, 1.24 (3s, 9H each, 3C(CH3)3),
1.23, 1.31 (2d, 3H each, 2CH(CH3)2), 4.04 (m, 1H, CH(CH3)2),
4.12–4.20 (m, 2H, H-5, H-6a), 4.31 (m, 1H, H-6b), 5.05 (s, 1H, H-
1), 5.36 (d, 1H, H-4), 5.49 (d, 1H, H-3); J3,4 = 10.1, J4,5 = 9.1,
JCH,CH3 = 6.2 Hz. 13C NMR (75.5 MHz, CDCl3): 21.8, 23.2 (CH(CH3)2),
27.0, 27.1 (C(CH3)3), 38.8, 38.9, 39.1 (C(CH3)3), 62.4 (C-6), 69.6 (C-
4), 72.7 (C-5), 72.9 (CH(CH3)2), 76.4 (C-3), 98.4 (C-1), 176.2, 177.4,
178.1 (COtBu), 191.9 (C-2). MS (FD): m/z 472 (M+). Anal. Calcd for
C24H40O9 (472.57): C, 61.00; H, 8.53. Found: C, 61.05; H, 8.61.
4.3.2. E-Oxime E-4a
The fraction eluted next (Rf 0.05) was treated as above to give
oxime E-4a (2.80 g, 51%) as a colorless foam; ½a D20
ꢁ74.1 (c 1.3,
ꢀ
CHCl3), ꢁ57.4 (c 1.3, CH2Cl2); 1H NMR (300 MHz, CDCl3): 1.15,
1.19 (2d, 6H, C(CH3)2), 4.08 (qq, 1H, CH(CH3)2), 4.30 (ddd, 1H, H-
5), 4.62 (two 1H-dd, 6-H2), 5.40 (s, 1H, H-1), 6.04 (dd, 1H, H-4),
6.60 (d, 1H, H-3), 7.30–8.05 (m, 15H, 3C6H5), 8.59 (s, 1H, NOH);
J3,4 = 6.7, J4,5 = 7.2, J5,6 = 5.5 and 4.8, J6,6 = 11.8, JCH,CH3 = 6.1 Hz; 13C
NMR (75.5 MHz, CDCl3): 21.4, 23.0 (CH(CH3)2), 63.6 (C-3), 64.5
(C-6), 69.4 (C-4), 69.9 (C(CH3)2), 72.3 (C-5), 95.0 (C-1), 125.3–
133.4 (3C6H5), 149.5 (C-2), 165.1, 165.2, 166.3 (3COC6H5). Anal.
4.3. Isopropyl 3,4,6,-tri-O-benzoyl-2-deoxy-2-hydroxyimino-b-
D-arabino-hexopyranoside E-4a and Z-4a
A solution of isopropyl uloside 3a13 (5.32 g, 10 mmol) and
NH2OHꢂHCl (1.40 g, 20 mmol) in MeOH/pyridine (30 mL, 1:1) was
stirred at room temperature for 24 h. Dilution with CH2Cl2

M. Lergenmüller et al. / Carbohydrate Research 344 (2009) 2127–2136
2133
Calcd for C30H29NO9 (547.56): C, 65.81; H, 5.34; N, 2.56. Found: C,
65.73; H, 5.28; N, 2.49.
127.6–128.5, 137.6–138.4 (3C6H5), 152.4 (C-2). Anal. Calcd for
C30H35NO6 (505.59): C, 71.26; H 6.98; N, 2.77. Found: C, 71.15;
H, 7.04; N, 2.69.
4.4. Isopropyl 2-deoxy-2-hydroxyimino-3,4,6-tri-O-pivaloyl-b-
4.5.2. E-Oxime
D
-arabino-hexopyranoside E-4b and Z-4b
Workup of the fraction eluted next gave 243 mg (21%) of E-4c as
a foam. ½a 2D0
ꢀ
ꢁ18.5 (c 1, CHCl3). 1H NMR (300 MHz, CDCl3). d 1.17,
Uloside 3b (1.6 g, 3.4 mmol) in THF/MeOH/pyridine (100 mL,
1.21 (2d, 3H each, CHMe2), 3.72–3.91 (m, 3H, H-5, 6-H2), 4.04 (dd,
1H, 4-H), 4.07 (m, 1H, CHMe2), 4.32–4.55 (m, 4H, 2CH2C6H5), 4.64,
4.72 (2d, 2H, CH2C6H5), 5.01 (d, 1H, 3-H), 5.26 (s, 1H, 1-H), 7.01–
7.54 (m, 15H, 3C6H5), 8.47 (s, 1H, NOH); J3,4 = 4.4, J4,5 = 5.2,
JCH2 = 11.6, JCH,CH3 = 6.1 Hz. 13C NMR (75.5 MHz, CDCl3) d 21.5,
23.2 (CHMe2), 69.5 (C-3), 69.7 (CH2C6H5), 70.6 (C-6), 71.9 (CHMe2),
72.5, 73.4 (2CH2C6H5), 74.5 (C-5), 75.8 (C-4), 95.2 (C-1), 127.7–
128.5, 137.6–138.5 (3C6H5), 152.8 (C-2). MS (FD): m/z 506
[M++H], 445 [M+ꢁC3H7OH].
70:20:10) was treated with NH2OHꢂHCl (596 mg, 8.6 mmol) and
stirred at room temperature for 2.5 h. Workup as described above
for 4a gave an amorphous 5:1 mixture (1H NMR) of E/Z isomers
(1.57 g, 94%). Elution from a silica gel column with 4:1 cyclohex-
ane/EtOAc and concentration of the first fraction (Rf 0.41 in 4:1
CCl4/EtOAc) yielded Z-4b (230 mg, 14%); ½a D20
ꢁ13.5 (c 1, CHCl3).
ꢀ
1H NMR (500 MHz, CDCl3): 1.19, 1.20, 1.23 (3s and m, 33H,
3C(CH3)3, 2CH(CH3)2), 4.06 (m, 1H, H-5), 4.11 (qq, 1H, CHMe2),
4.46 and 4.55 (two 1H-dd, 6-H2), 5.24 (dd, 1H, H-4), 5.42 (d, 1H,
H-3), 5.99 (s, 1H, H-1), 8.36 (br s, 1H, NOH); J3,4 = 4.7, J4,5 = 4.5,
J5,6 =6.0 and 7.4, J6,6 = 11.6 Hz. 13C NMR (75.5 MHz, CDCl3): 20.6,
22.5 (CH(CH3)2), 26.4, 26.5 (C(CH3)3), 38.1, 38.2 (C(CH3)3), 63.7
(C-6), 67.1 (C-3), 67.5 (C-4), 70.0 (CH(CH3)2), 71.7 (C-5), 87.9 (C-
1), 148.1 (C-2), 176–1. 177.7 (3tBuCO).
4.6. Isopropyl 3,4,6-tri-O-benzoyl-2-benzoyloxyimino-2-deoxy-
b-D-arabino-hexopyranoside 5a
4.6.1. Z-Isomer by glycosidation of bromide 2a
Silver carbonate (138 mg, 0.50 mmol), i-PrOH (115 L,
1.51 mmol), and molecular sieve (4 Å, 500 mg) were suspended
in CH2Cl2 (5 mL) and stirred for 15 min at room temperature in
the dark. Bromide 12a10 (200 mg, 0.36 mmol) was added and stir-
ring was continued for 2.5 h. The mixture was filtered, freed from
the solvent in vacuo and eluted from a silica gel column with 10:1
toluene/EtOAc. Evaporation of the solvent afforded Z-5a (174 mg,
E-4b. The fraction eluted next (Rf 0.34 in 4:1 CCl4/EtOAc) was
processed as described above to afford E-4b as a colorless solid
(720 mg, 43%); ½a D20
ꢀ
ꢁ14.4 (c 1, CHCl3). 1H NMR (500 MHz, CDCl3):
1.17, 1.18, 1.22 (3s and m, 33H, 3C(CH3)3, 2CH(CH3)2), 3.96 (ddd,
1H, H-5), 4.04 (qq, 1H, CH(CH3)2), 4.29 and 4.34 (two 1H-dd, 6-
H2), 5.26 (s, 1H, H-1), 5.59 (dd, 1H, H-4), 6.08 (d, 1H, H-3), 8.46
(br s, 1H, NOH); J3,4 = 6.7, J4,5 = 7.7, J5,6 = 3.9 and 5.2, J6,6 = 12.0,
JCH,CH3 = 6.1 Hz. 13C NMR (75.5 MHz, CDCl3): 20.8, 22.3 (CH(CH3)2),
26.4, 26.5 (C(CH3)3), 38.1, 38.2 (C(CH3)3), 62.7 (C-3, C-6), 67.3 (C-4),
68.5 (CH(CH3)2), 71.3 (C-5), 94.1 (C-1), 149.0 (C-2), 176.1, 177.7
(3tBuCO). MS (FD) data: m/z 487 (M+). Anal. Calcd for C24H41NO9
(487.59): C, 59.12; H, 8.48; N, 2.87. Found: C, 59.17; H, 8.52; N,
2.84.
89%) as a colorless foam; Rf = 0.53 (10:1 toluene/EtOAc); ½a D20
ꢀ
ꢁ60.7 ? ꢁ21.2 (1 h, c 0.8, CHCl3); ꢁ71.0 (c 1, CH2Cl2). 1H NMR
(500 MHz, CDCl3): 1.27, 1.34 (2d, 6H, CH(CH3)2), 4.28 (qq, 1H,
CH(CH3)2), 4.47 (dt, 1H, H-5), 4.86 (2H-d, 6-H2), 5.91 (dd, 1H,
H-4), 6.19 (s, 1H, H-1), 6.20 (d, 1H, H-3), 7.32–8.08 (m, 20H,
4C6H5); J3,4 = 5.0, J4,5 = 4.8, J5,6 = 6.6, JCH,CH3 6.1 Hz. 13C NMR
(75.5 MHz, CDCl3): 21.6, 23.2 (CH(CH3)2), 64.8 (C-6), 68.7 (C-3),
69.2 (C-4), 71.5 (CH(CH3)2), 72.8 (C-5), 90.4 (C-1), 128.3–133.8
(4C6H5), 156.9 (C-2), 162.8, 164.6, 165.0, 166.0 (4COC6H5). Anal.
Calcd for C37H33NO10 (651.67): C, 68.20; H, 5.10; N, 2.15. Found:
C, 67.98; H, 4.99; N, 2.07.
NOESY experiments. Irradiation of the Z-4b signal at 5.99 (H-1)
affected those at 4.06 (H-5), 5.42 (H-3), and 9.36 (N–OH), whilst, in
turn, H-3 irradiation resulted in inversion of the signals for H-1, H-
5, and NOH. The E-4b isomer, by contrast, showed no change in the
NOH signal at 8.46 ppm on irradiation with H-1 (5.26 ppm).
NOESY experiments. Irradiation of the signal at 6.19 ppm (H-1)
affected those at 4.47 (H-5).
4.5. Isopropyl 3,4,6-tri-O-benzyl-2-deoxy-2-hydroxyimino-b-
D-
arabino-hexopyranosides E-4c and Z-4c
4.6.2. E and Z isomer 5a by benzoylation of the E/Z-oxime
mixture 4a
Uloside 3c13 (1.15 g, 2.3 mmol) was dissolved in THF and pyri-
dine (50 mL each, followed by the addition of NH2OHꢂHCl (1.0 g,
14.4 mmol) and stirring at ambient temperature for 1.5 h. The mix-
ture was diluted with CH2Cl2 (100 mL) and poured into ice-water
(200 mL). Consecutive washings of the organic phase with 2 M
HCl (2 ꢃ 75 mL), satdNaHCO3 solution (50 mL), and water
(50 mL), drying (Na2SO4) and removal of the solvent in vacuo left
a syrup which contained the oximes in a 1:2 E/Z ratio (1H NMR).
Rf (Z-oxime) = 0.47 (5:1 toluene/EtOAc); Rf (E-oxime) = 0.40.
Benzoyl chloride (1.70 mL, 14.3 mmol) was added dropwise to a
solution of oxime mixture 4a (3.12 g, 5.71 mmol) in CHCl2 (20 mL)
and pyridine (2.3 mL) at 0 °C, followed by stirring for 24 h at room
temperature. The solution was diluted with CH2Cl2 (10 mL),
washed with 2 M HCl (20 mL), satd NaHCO3 (20 mL), and water
(20 mL), dried (Na2SO4) and concentrated under reduced pressure
to yield a colorless syrup, comprising a 2:1 mixture of E-ben-
zoyloxime (Rf = 0.10 in 3:1 CH2Cl2/toluene) and
Z isomer
(Rf = 0.13). Elution from a silica gel column with 2:1 CH2Cl2/cyclo-
hexane and concentration of the first fraction gave 370 mg (10%) of
Z-5a as a hard foam of ½a D20
ꢀ
ꢁ69.9 (c 1, CH2Cl2), identical by 1H and
4.5.1. Z-Oxime
13C NMR with the product described under 4.6.1.
Chromatography of the syrupy E/Z-mixture of oximes obtained
on silica gel (4 ꢃ 22 cm column, elution with 10:1 toluene/EtOAc)
and evaporation of the fraction eluted first to dryness in vacuo gave
The fraction eluted next upon evaporation to dryness in vacuo
gave the E-benzoyloxime E-5a (1.0 g, 27%) as an amorphous foam;
485 mg (42%) of Z-4c as a colorless syrup; ½a D20
ꢁ35.1 (c 1, CHCl3).
ꢀ
½
a 2D0
ꢀ
ꢁ7.9 ? ꢁ21.5 (1 h, c 1.1, CHCl3); –3.5 (c 1.0, CH2Cl2). 1H NMR
1H NMR (300 MHz, CDCl3). d 1.16, 1.20 (2d, 6H, CHMe2), 3.72–3.89
(m, 4H, 6-H2, 5-H, 4-H), 4.09 (d, 1H, 3-H), 4.11 (m, 1H, CHMe2), 4.44
(m, 5H, 2CH2C6H5, CH2aC6H5), 4.71 (d, 1H, CH2bC6H5), 5.88 (s, 1H, 1-
H), 7.18–7.38 (m, 15H, 3C6H5), 8.50 (s, 1H, NOH); J3,4 = 2.4,
JCH2 = 11.7, JCH,CH3 = 6.1 Hz. 13C NMR (75.5 MHz, CDCl3) d 21.6,
23.3. (CHMe2), 70.4 (CH2C6H5), 70.9 (C-6), 71.2 (CHMe2), 71.9,
73.4 (2CH2C6H5), 74.2 (C-5), 75.3 (C-3), 76.7 (C-4), 90.5 (C-1),
(500 MHz, CDCl3): 1.25, 1.27 (2d, 6H, CH(CH3)2), 4.20 (qq, 1H,
CH(CH3)2), 4.43 (ddd, 1H, H-5), 4.69 and 4.84 (two 1H-dd, 6-H2),
5.70 (s, 1H, H-1), 6.19 (dd, 1H, H-4), 6.73 (d, 1H, H-3), 7.30–8.10
(m, 20H, 4C6H5); J3,4 = 6.9, J4,5 = 7.3, J5,6 = 5.4 and 5.1, J6,6 = 11.8,
JCH,CH3 = 6.0 Hz; 13C NMR (75.5 MHz, CDCl3): 21.8, 23.1 (CH(CH3)2),
64.5 (C-6), 64.6 (C-3), 69.4 (C-4), 71.0 (C(CH3)2), 72.3 (C-5), 95.0 (C-
1), 127.7–133.9 (4C6H5), 156.3 (C-2), 163.3, 165.1, 165.2, 166.2

2134
M. Lergenmüller et al. / Carbohydrate Research 344 (2009) 2127–2136
(4COC6H5). Anal. Calcd for C37H33NO10 (651.67): C, 68.20; H, 5.10;
N, 2.15. Found: C, 67.97; H, 5.07; N, 2.14.
(C(CH3)2), 27.0, 27.1, 27.2 (C(CH3)3), 38.7, 38.8, 38.9 (C(CH3)3),
63.2 (C-6), 64.2 (C-3), 68.0 (C-4), 70.3 (CMe2), 72.0 (C-5), 94.7 (C-
1), 127.7–134.0 (C6H5), 156.4 (C-2), 163.2 (COC6H5), 176.6, 176.7,
178.2 (COtBu). MS (FD): m/z 591 (M+), 490 (M+ꢁPivO/tBuCO2).
Anal. Calcd for C31H45NO10 (591.68): C, 62.93; H, 7.67; N, 2.37.
Found: C, 63.01; H, 7.72; N, 2.23.
4.7. Isopropyl 2-benzoyloxyimino-2-deoxy-3,4,6-tri-O-pivaloyl-
b-D-arabino-hexopyranosides E-5b and Z-5b
4.7.1. Z-Oxime by glycosidation of bromide 2b
X-ray diffraction analysis was carried out on an Enraf-Nonius
A suspension of bromide 2b (1.14 g, 1.9 mmol), silver carbonate
(2.6 g, 9.4 mmol), i-PrOH (288 L, 3.7 mmol) and molecular sieve
(3 Å, 1.5 g) in dry CH2Cl2 (40 mL) was stirred at room temperature
for 18 h. The mixture was filtered, and freed from the solvent in va-
CAD diffractometer with graphite monochromated MoKa radiation
(k = 0.71073 Å). Details for crystal data, data collection, and refine-
ment parameters are given in Table 5. Programs used for structure
solution, refinement, and analysis include SHELXS97,26 and SHEL-
XS97.27 The hydrogen atoms are geometrically positioned; the iso-
propyl group is disordered and the bonds of C9–C10, C9–C11 are
fixed at 1.50 Å and not refined. Stereostructure: Figure 1; selected
torsional angles: Table 2; deviations from the least-squares best-fit
plane and ring puckerings: Table 3.
cuo to yield Z-5b (920 mg, 83%) as an amorphous product; ½a D20
ꢀ
ꢁ59.5 ? +56.8 (after 24 h, c 0.9, CHCl3); –61.7 (c 1.1, CH2Cl2). 1H
NMR (300 MHz, CDCl3): 1.21, 1.24, 1.25 (three 9H-s, 6H-m,
3C(CH3)3, C(CH3)2), 4.08 (m, 1H, H-5), 4.18 (m, 1H, CH(CH3)2),
4.43 and 4.52 (two 1H-dd, 6-H2), 5.34 (dd, 1H, H-4), 5.72 (d, 1H,
H-3), 6.04 (s, 1H, H-1), 7.45–8.05 (m, 5H, C6H5); J3,4 = 5.2,
J4,5 = 5.0, J5,6 = 5.7 and 7.7, J6,6 = 11.5 Hz. 13C NMR (75.5 MHz,
CDCl3): 21.3, 23.1 (C(CH3)2), 27.0, 27.1 (C(CH3)3), 38.8, 38.9
(C(CH3)3), 64.2 (C-6), 67.7 (C-3, C-4), 71.0 (C(CH3)2), 72.7 (C-5),
89.7 (C-1), 128.3–133.7 (C6H5), 156.5 (C-2), 162.7 (COC6H5),
176.3, 176.7, 178.1 (3COtBu), JC-1,1-H = 171.9 Hz. MS (FD): m/z 591
(M+). Anal. Calcd for C31H45NO10 (591.68): C, 62.93; H, 7.67; N,
2.37. Found: C, 62.86; H, 7.66; N, 2.36.
4.8. Isopropyl 3,4,6-tri-O-benzyl-2-benzoyloxyimino-2-deoxy-
b-D
-arabino-hexopyranosides E-5c and Z-5c
To a cooled (0 °C) solution of 2.8 g (5.5 mmol) of E/Z-oxime mix-
ture 5c in CH2Cl2 (50 mL) were added pyridine (1.5 mL) and drop-
wise benzoyl chloride (1.0 mL, 8.6 mmol), followed by stirring for
4 h at 0 °C. The mixture was then poured on ice-water (75 mL), ex-
tracted with CH2Cl2 (2 ꢃ 50 mL) and followed by consecutive
washings of the combined organic phases with 2 M HCl
(2 ꢃ 30 mL), satd NaHCO3 solution (2 ꢃ 50 mL), and water. Drying
(Na2SO4) and evaporation to dryness in vacuo gave a syrup com-
prising a 5:2 mixture (1H NMR) of Z- and E-isomers. Separation
was effected by elution from a silica gel column (3 ꢃ 18 cm) with
10:1 toluene/EtOAc.
4.7.2. E-Isomer by benzoylation of E/Z-oxime mixture 4b
A solution of 1.2 g (2.4 mmol) of the 5:1-mixture of E-4b/Z-4b
(as obtained under 4.4.) in CH2Cl2 (30 mL), pyridine (1 mL), and
benzoyl chloride (685 L, 5.9 mmol) was kept at room temperature
for 2 h and subsequently processed as described above (4.6.2.) to
afford 1.34 g (96%) of an 8:1 E/Z amorphous mixture (1H NMR).
Crystallization from i-PrOH gave benzoyloxime E-5b as colorless
prisms (1.2 g, 85%); mp 130–131 °C; ½a D20
ꢀ
+85.3 ? +60.5 (after
4.8.1. Z-Benzoyloxime
24 h, c 0.9, CHCl3); +85.1 (c 1, CH2Cl2). 1H NMR (300 MHz, CDCl3):
1.13, 1.16, 1.24 (3s, 27H, 3C(CH3)3), 1.25, 1.30 (2d, 6H, 2C(CH3)2),
4.04 (ddd, 1H, H-5), 4.13 (qq, 1H, CHMe2), 4.33 and 4.37 (two
1H-dd, 6-H2), 5.56 (s, 1H, H-1), 5.71 (dd, 1H, H-4), 6.31 (d, 1H, H-
3), 7.46–8.18 (m, 5H, C6H5); J3,4 = 6.9, J4,5 = 8.2, J5,6 = 3.8 and 4.9,
J6,6 = 12.0, JCH,CH3 = 6.2 Hz. 13C NMR (75.5 MHz, CDCl3): 21.8, 23.0
The fraction eluted first contained Z-5c of Rf = 0.56 (5:1 toluene/
EtOAc) and, upon evaporation to dryness in vacuo gave 0.77 g
(23%) of a colorless syrup. ½a D20
ꢀ
ꢁ27.5 (c 1, CHCl3). 1H NMR
(300 MHz, CDCl3). d 1.20, 1.23 (2d, 6H, CHMe2), 3.75–3.94 (m, 4H,
6-H2, 5-H, 4-H), 4.18 (m, 1H, CHMe2), 4.36–4.51 (m, 5H, 3-H,
2CH2C6H5), 4.60, 4.80 (2d, 2H, CH2C6H5), 6.00 (s, 1H, 1-H), 7.1–
7.7, 8.0–8.2 (m, 20H, 4C6H5); J3,4 = 2.8, J4,5 = 5.1, JCH2 = 11.7,
JCH,CH3 = 6.1 Hz. 13C NMR (75.5 MHz, CDCl3) d 21.6, 23.3 (CHMe2),
70.5 (C-6), 70.8 (CH2C6H5), 71.7 (CHMe2), 71.6, 73.4 (2CH2C6H5),
74.3 (C-4), 74.9 (C-3), 76.5 (C-5), 90.8 (C-1), 127.6–128.5, 137.6–
138.2 (4C6H5), 159.2 (C-2), 162.4 (C6H5CO). Anal. Calcd for
C37H39NO7 (609.69): C, 72.88; H, 6.45; N, 2.30. Found: C, 72.69;
H, 6.35; N, 2.20.
Table 5
Crystal data and structure refinement for E-5b
Empirical formula
Formula weight (g)
Temperature (K)
Wavelength (Å)
Crystal system, space group
A (Å)
C31H45NO10
591.68
299(2)
0.71073
Trigonal, R3
27.692(4)
4.8.2. E-Benzoyloxime
B (Å)
27.692(4)
Further elution resulted in an E/Z mixed fraction (1.6 g, 48%) be-
fore pure E-5c (Rf = 0.46 in 5:1 toluene/EtOAc) appeared. Evapora-
C (Å)
11.747(4)
90
90
120
7801.3
9, 1.13
a
(°)
tion to dryness in vacuo afforded 0.71 g (21%) of a syrup of ½a D20
ꢀ
b (°)
c
(°)
ꢁ9.1 (c 1.1, CHCl3). 1H NMR (300 MHz, CDCl3). d 1.21, 1.23 (2d,
6H, CMe2), 3.77–3.96 (m, 3H, 5-H, 6-H2), 4.16 (m, 1H, CHMe2),
4.25 (dd, 1H, 4-H), 4.41–4.82 (m, 6H, 3CH2C6H5), 5.06 (d, 1H, 3-
H), 5.54 (d, 1H, 1-H), 7.17–7.61, 7.87–8.12 (m, 20H, 4C6H5);
J1,3 = 0.5, J3,4 = 4.9, J4,5 = 5.4, JCH2 = 11.6, JCH,CH3 = 6.1 Hz. 13C NMR
(75.5 MHz, CDCl3) d 21.6, 23.1 (CHMe2), 70.2 (C-6), 70.5 (CHMe2),
71.2 (CH2C6H5), 71.3 (C-3), 72.8, 73.3 (2CH2C6H5), 74.2 (C-5), 75.4
(C-4), 94.9 (C-1), 127.7–128.5, 137.6–138.5 (4C6H5), 159.2 (C-2),
163.4 (C6H5CO). MS (FD): m/z 609 [M+], 549 [M+ꢁC6H5CH2O].
Volume (A3)
Z, Dcalcd (g(/cm3)
Crystal size (mm3)
h Range for data collection (°)
Limiting indices
0.30 ꢃ 0.25 ꢃ 0.18
1.47–22.97
ꢁ30 6 h 6 14, 0 6 k 6 30,
0 6 l 6 12
2251/2251 [0.0000]
93.4
0.99850 and 0.9752
Full-matrix least-squares on F2
2251/77/378
1.001
R1 = 0.0985, wR2 = 0.1949
R1 = 0.1011, wR2 = 0.2020
1043(33)
Reflections collected/unique [R(int)]
Completeness to h = 22.97 (%)
Maximum and minmium transmission
Refinement method
Data/restraints/parameters
Goodness-of-fit on F2
4.9. 1,2:3,4-Di-O-isopropylidene-6-O-(30,40,60-tri-O-benzoyl-2-
deoxy-b-D-arabino-hexopyranos-2-ulosyl)-D-galactopyranose 6
Final R indices [I > 2
R indices (all data)
Extinction coefficient
Largest difference in peak and hole
(e Aꢁ3
r(I)]
mixture of diacetone–galactose28 (210 mg, 0.81 mmol),
molecular sieve 3 Å and Ag2CO3 (1.1 g, 4 mmol) in CH2Cl2
0.439 and ꢁ0.230
A
)

M. Lergenmüller et al. / Carbohydrate Research 344 (2009) 2127–2136
2135
(20 mL) was stirred in the dark for 15 min followed by the addition
of ulosyl iodide 2a (with I instead of Br)13 and continuous stirring.
As no ulosyl iodide was detectable by TLC after 5 min, the mixture
was diluted with 20 mL of CH2Cl2, filtered through Kieselgur,
washed with 10% Na2S2O3 solution (20 mL) and water
(2 ꢃ 20 mL). Drying over Na2SO4 and removal of the solvent in va-
cuo gave 425 mg (83%) of a colorless foam, which turned out (1H
NMR) to be a mixture of keto form 6 and its hydrate (6ꢂH2O). MS
(FD, 20 mA): m/z = 733 (M++H), 717 (M+ꢁCH3). 1H NMR
(300 MHz, CDCl3) for keto form: d 1.30–1.53 (four 3H-s, 4 Me),
3.7–4.7 (complex m, H-20–60-H2, 5-H, 6-H2), 5.40 (1H-s, H-10),
5.57 (1H-d, H-1), 5.93 (1H-dd, H-4), 5.99 (1H-d, H-3); J1,2 = 4.7,
96.4 (C-1), 108.9 and 109.5 (2C(CH3)2), 125.4–133.6 (3C6H5),
148.9 (C-2), 165.1–166.2 (3COC6H5).
4.11. 1,2:3,4-Di-O-isopropylidene-(3,4,6-tri-O-benzoyl-2E-
benzoyloxyimino-2-deoxy-b-
galactopyranose 8E
D-arabino-hexopyranosyl)-a-D-
To a cooled (0 °C) solution of the 5:1 oxime mixture 7E/7Z
(1.3 g, 1.7 mmol) as newly prepared according to 4.10 (cf. above)
in CH2Cl2 (75 mL) was added dropwise 1.4 mL (12 mmol) of ben-
zoyl chloride. Stirring was continued for 15 h allowing the mixture
to warm to room temperature, followed by pouring into ice-water
(50 mL) and extraction with CH2Cl2 (25 mL). Consecutive washing
of the organic phase with 50 mL each of 2 M HCl, satd NaHCO3-
solution and water gave 1.56 g (94%) of a syrupy solid comprising
an approximate 20:1 E/Z mixture (1H NMR). It was subjected to
elution from a silica gel column (4 ꢃ 22 cm) with 15:1 toluene/
EtOAc. Collection of the fraction with Rf = 0.41 (5:1 toluene/EtOAc)
J3 ,4 = 10.0, J4 ,5 = 10.1 Hz. 13C NMR (75.5 MHz, CDCl3), relevant sig-
nals: d 76.7 (C-30), 96.2 (C-1), 99.3 (C-10), 191.6 (C-20).
0
0
0
0
Hydrate (6ꢂH2O): 1H NMR (300 MHz, CDCl3), relevant signals:
4.81 (1H-s, H-10), 5.53 (1H-d, H-1), 5.61 (1H-dd, H-30), 5.79 (1H-
d, H-40), J3,4 = 5.3, J4,5 = 9.8 Hz. 13C NMR (75.5 MHz, CDCl3): 63.5
(C-60), 68.4 (C-6), 75.6 (C-30), 92.8 (C-20), 96.2 (C-1), 102.7 (C-10).
afforded 1.23 g (74%) of 8E as a colorless foamy solid of ½a D20
ꢁ35.5
ꢀ
4.10. 1,2:3,4-Di-O-isopropylidene-6-O-(3,4,6-tri-O-benzoyl-2-
(c 1.0, CHCl3). 1H NMR (300 MHz, CDCl3): d 1.29, 1.34, 1.42, 1.58
(4s, 12H, C(CH3)2), 3.78 (dde, 1H, 6-Ha), 3.92 (dd, 1H, 4-H), 4.07
(m, 1H, 5-H), 4.14 (dd, 1H, 6-Hb), 4.31 (dd, 1H, 2-H), 4.43 (m, 1H,
50-H), 4.51 (dd, 1H, 30-H), 4.63 and 4.87 (two 1H-dd, 60-H2), 5.55
(d, 1H, 1-H), 5.67 (s, 1H, 10-H), 6.25 (dd, 1H, 40-H), 6.74 (d, 1H, 30-
deoxy-2-hydroxyimino-b-
D-arabino-hexopyranosyl)-a-D-
galactopyranose 7E and 7Z
Silver-alumina silicate29 (2 g, 6.6 mmol) and freshly desiccated
molecular sieve 3 Å was added to a solution of diacetone–galact-
ose28 (2.5 g, 9.5 mmol) followed by stirring for 30 min in the dark,
and cooling to 0 °C with ice, and the addition of 4.0 g (7.2 mmol) of
ulosyl bromide 2a.13 After 30 min, the mixture was filtered over
Kieselgur and the filtrate was taken to dryness in vacuo to give ulo-
side 6 as a colorless foam, which was dissolved in a mixture of THF
(75 mL) and pyridine (150 mL), followed by the addition of
NH2OHꢂHCl (3.0 g, 42 mmol). Stirring at ambient temperature for
2 d, dilution with CH2Cl2 (200 mL), pouring into ice-water
(200 mL), and consecutive washings of the organic phase with
2 M HCl (2 ꢃ 150 mL), satd NaHCO3 solution (2 ꢃ 150 mL) and
water (2 ꢃ 150 mL), drying and evaporation to dryness in vacuo
left a foam comprising (1H NMR) a 5:1 mixture of 7E and 7Z. Chro-
matography on silica gel (5 ꢃ 30 cm column) was effected by elu-
tion with 10:1 toluene/EtOAc.
0
0
H), 7.25–8.12 (m, 20H, 4C6H5); J3,4 = 7.1, J4,5 = 8.3, J5 ,6 = 4.5 and
0
0
0
0
0
0
5.4, J6 ,6 = 11.9, J1,2 = 5.0, J2,5 = 2.4, J3 ,4 = 7.9, J4 ,5 = 1.7, J5,6 = 6.0
and 6.3, J6,6 = 8.9 Hz. 13C NMR (75.5 MHz, CDCl3): d 24.7, 25.5,
26.3, 26.6 (2C(CH3)2), 64.6 (C-60), 65.1 (C-30), 67.0 (C-5), 67.5 (C-
6), 69.7 (C-40), 71.0 (C-2, C-3), 71.2 (C-4), 72.5 (C-5), 96.7 (C-1),
97.3 (C-1), 109.2 and 109.9 (2C(CH3)2), 128.0–134.1 (4C6H5),
155.9 (C-20), 163.4–166.4, 171.6 (4COC6H5). Anal. Calcd for
C46H45NO15 (851.83): C, 64.85; H, 5.32; N, 1.64. Found: C, 64.73;
H, 5.20; N, 1.57.
A fraction eluted last proved to be an approximate 1:2 mixture
of 8E and 8Z, from which the NMR data for the Z isomer could
readily be gathered. They proved to be identical with those of an
independently prepared 8Z, that is, by Ag2CO3-promoted glycosi-
dation of Z-benzoximino-ulosyl bromide 13a with diacetone-
galactose.14a
The E-oxime 7E of Rf = 0.52 (2:1 toluene/EtOAc) was eluted first,
affording 1.88 g (39%, based on 2a) of a colorless foam; ½a D20
ꢁ79.8
ꢀ
(c 0.98, CHCl3). 1H NMR (300 MHz, CDCl3): d 1.25, 1.32, 1.39, 1.53
(4s, 12H, C(CH3)2), 3.68 (dd, 1H, 6-Ha), 3.74 (dd, 1H, 4-H), 4.00
(m, 2H, 5-H, 6-Hb). 4.23 (m, 1H, 50-H), 4.29 (dd, 1H, 2-H), 4.45
(dd, 1H, 3-H), 4.49 and 4.79 (two 1H-dd, 6-H2), 5.36 (s, 1H, 10-H),
5.54 (d, 1H, 1-H), 6.17 (dd, 1H, 40-H), 6.58 (d, 1H, 30-H), 7.34–
4.12. 3,4,6-Tri-O-pivaloyl-1,5-anhydro-D-fructose Z-oxime 11b
To a solution of hydroxyglucal ester 10b13 (10 g, 20 mmol) in
dry pyridine (250 mL) was added NH2OHꢂHCl (9.7 g, 140 mmol).
The mixture was stirred for 5 d at 70 °C, diluted with CH2Cl2
(300 mL) and was subsequently washed with 2 M HCl (500 mL),
sat NaHCO3 (200 mL), water (200 mL), and dried (Na2SO4). Re-
moval of the solvent in vacuo left a crystalline residue, which
was recrystallised from i-PrOH to yield 11b (6.8 g, 79%) as colorless
0
0
0
0
8.04 (m, 15H, 3C6H5), 8.84 (s, 1H, NOH); J3 ,4 = 7.1, J4 ,5 = 8.6,
0
0
0
0
J5 ,6 = 4.1 and 4.9, J6 ,6 = 11.9, J1,2 = 4.9, J2,3 = 2.4, J3,4 = 7.9, J4,5 = 1.5,
J5,6a = 8.7, J6,6 = 11.2 Hz. 13C NMR (75.5 MHz, CDCl3): d 24.3, 25.2,
25.9, 26.2 (2C(CH3)2), 63.9 (C-30), 64.1 (C-60), 66.7 (C-60), 67.2 (C-
50), 69.4 (C-40), 70.7 (C-2, C-3), 70.9 (C-4), 71.9 (C-50), 96.4 (C-1),
97.2 (C-10), 108.9 and 109.5 (2C(CH3)2), 125.3–133.4 (3C6H5),
148.7 (C-20), 165.1–166.2 (3COC6H5). Anal. Calcd for C27H22NO9
(667.78): C, 70.14; H, 6.20; N, 2.10. Found: C, 70.03; H, 6.34; N,
2.00.
needles; mp 164–166 °C;
½
a 2D0
ꢀ
ꢁ12.3 (c 1, CHCl3). 1H NMR
(300 MHz, CDCl3): 1.18, 1.20, 1.22 (3s, 27H, 3C(CH3)3), 3.73 (ddd,
1H, H-5), 3.98 (d, 1H, H-1a), 4.18–4.21 (m, 2H, 6-H2), 5.17 (d, 1H,
H-1e), 5.22 (dd, 1H, H-4), 5.56 (d, 1H, H-3), 8.56 (br s, 1H, NOH);
J1,1 = 15.4, J3,4 = 8.3; J4,5 = 8.7; J5,6 = 4.8 and 2.9 Hz. 13C NMR
(75.5 MHz, CDCl3): 25.2, 27.0, 27.1 (C(CH3)3), 38.8, 38.9 (C(CH3)3),
61.7 (C-1), 62.4 (C-6), 68.8 (C-4), 70.5 (C-3), 76.3 (C-5), 150.8 (C-
2), 176.4, 177.4, 178.3 (COtBu). MS (FD): m/z 429 (M+), 328
(M+ꢁPivO/tBuCO2). Anal. Calcd for C21H35NO8 (429.51): C, 58.72;
H, 8.21; N, 3.26. Found: C, 58.65; H, 8.28; N, 3.14.
The minor product, Z-oxime 7Z of Rf = 0.48, was eluted next:
530 mg (11%) of a colorless foam. 1H NMR (300 MHz, CDCl3): d
1.24, 1.32, 1.39, 1.53 (4s, 12H, C(CH3)2), 3.68 (dd, 1H, 6-Ha), 3.73
(dd, 1H, 4-H), 4.02 (m, 2H, 5-H, 6-Hb), 4.29 (dd, 1H, 2-H), 4.45
(dd, 1H, 3-H), 4.51 (m, 1H, 50-H), 4.83 (d, 2H, 60-H), 5.54 (d, 1H,
1-H), 5.87 (dd, 1H, 40-H), 6.00 (d, 1H, 30-H), 6.02 (s, 1H, 10-H),
0
0
4.13. 3,4,6-Tri-O-pivaloyl-1,5-anhydro-D-fructose Z-
7.15–8.04 (m, 15H, 3C6H5), 8.74 (s, 1H, NOH); J4 ,4 = 6.0,
0
0
0
0
benzoyloxime 12b
J4 ,5 = 5.6, J5 ,6 = 6.3, J1,2 = 4.9, J2,3 = 2.4, J3,4 = 7.8, J4,5 = 1.5,
J5,6a = 8.7, J6,6 = 11.4 Hz. 13C NMR (75.5 MHz, CDCl3): d 24.3, 25.0,
25.9, 26.2 (2C(CH3)2), 65.0 (C-60), 66.7 (C-6), 67.2 (C-5), 68.7 (C-
30), 69.0 (C-40), 70.6 (C-2, C-3), 70.9 (C-4), 72.9 (C-50), 91.7 (C-10),
A solution of oxime 11b (2.6 g, 6 mmol) in CH2Cl2/pyridine
(60 mL, 5:1) and benzoyl chloride (1.7 mL, 15 mmol) was stirred

2136
M. Lergenmüller et al. / Carbohydrate Research 344 (2009) 2127–2136
48–52; (c) Boren, H. B.; Ekborg, G.; Lönngren, J. Acta Chem. Scand. 1975, B29,
1085–1088.
for 20 h at room temperature. Dilution with CH2Cl2 (50 mL), wash-
ing with 2 M HCl (200 mL), satd aq NaHCO3 (100 mL), and water
(100 mL), drying (Na2SO4) and removal of the solvent in vacuo gave
12b (2.81 g, 88%) in microcrystalline form; recrystallization of an
analytic sample from i-PrOH afforded 12b as colorless needles;
3. (a) Lichtenthaler, F. W.; Kaji, E.; Weprek, S. J. Org. Chem. 1985, 50, 3505–3515;
(b) Lichtenthaler, F. W.; Kaji, E. Liebigs Ann. Chem. 1985, 1659–1668; (c) Kaji, E.;
Lichtenthaler, F. W. J. Carbohydr. Chem. 1975, 14, 791–803; (d) Kaji, E.;
Lichtenthaler, F. W.; Osa, Y.; Zen, S. Bull. Chem. Soc. Jpn. 1995, 68, 1172–1179;
(e) Kaji, E.; Matsui, E.; Kobayashi, M.; Zen, S. Bull. Chem. Soc. Jpn. 1995, 68,
1449–1454.
4. (a) Karpiesiuk, W.; Banaszek, A. J. Carbohydr. Chem. 1990, 9, 909–914; (b)
Banaszek, A.; Karpiesiuk, W. Carbohydr. Res. 1994, 251, 233–242 (c) 1994, 251,
243–253.
5. For reviews, see: (a) Kaji, E.; Lichtenthaler, F. W. Trends Glycosci. Glycotechnol.
1993, 5, 121–142; (b) Gridley, J. J.; Osborn, H. M. I. J. Chem. Soc., Perkin Trans. 1
2000, 1477–1491.
6. (a) Lemieux, R. U.; Nagabhushan, T. L.; Gunner, S. W. Can. J. Chem. 1968, 46,
405–411; (b) Lemieux, R. U.; Ito, Y.; James, K.; Nagabushan, T. L. Can. J. Chem.
1973, 51, 7–18; (c) Lemieux, R. U.; Earl, R. A.; James, K.; Nagabhushan, T. L. Can.
J. Chem. 1973, 51, 19–26.
mp 126–127 °C; ½a D20
ꢀ
ꢁ44.2 (c 1, CHCl3). 1H NMR data (300 MHz,
CDCl3): 1.20, 1.23, 1.30 (3s, 27H, 3C(CH3)3), 3.85 (m, 1H, H-5),
4.16 (d, 1H, H-1a), 4.23 (m, 2H, 6-H2), 5.29 (d, 1H, H-1e), 5.38
(dd, 1H, H-4), 5.78 (d, 1H, H-3), 7.44–8.01 (m, 5H, C6H5);
J1,1 = 15.2, J3,4, = J4,5 = 9.0 Hz. 13C NMR (75.5 MHz, CDCl3): 27.0,
27.1 (C(CH3)3), 38.8, 38.9 (C(CH3)3), 62.0 (C-6), 62.6 (C-1), 68.2
(C-4), 70.5 (C-3), 76.7 (C-5), 128.3–133.7 (C6H5), 158.0 (C-2),
162.6 (COC6H5), 176.2, 177.4, 178.1 (COtBu). MS (FD): m/z 533
(M+). Anal. Calcd for C28H39NO9 (533.62): C, 63.02; H, 7.37; N,
2.62. Found: C, 62.95; H, 7.31; N, 2.55.
7. Ciunik, Z.; Szweda, R.; Smiatacz, Z. Carbohydr. Res. 1991, 219, 9–13.
8. Ciunik, Z.; Paulsen, H.; Luger, P.; Smiatacz, Z.; Msyzka, H. Acta Crystallogr., Sect.
B 1989, 45, 512–518.
9. Kaji, E.; Osa, Y.; Takahashi, K.; Zen, S. Chem. Pharm. Bull. 1996, 44, 15–20.
10. Lichtenthaler, F. W.; Jarglis, P.; Hempe, W. Liebigs Ann. Chem. 1983, 1959–1972.
11. Brehm, M.; Göckel, V. H.; Jarglis, P.; Lichtenthaler, F. W. Tetrahedron:
Asymmetry 2008, 19, 358–373.
4.14. 2Z-(Benzoyloxyimino)-2-deoxy-3,4,6-tri-O-pivaloyl-
arabino-hexopyranosyl bromide 13b
a-D-
12. (a) Larm, O.; Scholander, E.; Theander, O. Carbohydr. Res. 1976, 49, 69–77; (b)
Micheli, E.; Nicotra, F.; Panza, L.; Ronchetti, F.; Toma, L. Carbohydr. Res. 1985,
129, C1–C3.
13. Lichtenthaler, F. W.; Kläres, U.; Lergenmüller, M.; Schwidetzky, S. Synthesis
1992, 179–184.
14. (a) Kaji, E.; Lichtenthaler, F. W.; Nishino, T.; Yamane, A.; Zen, S. Bull. Chem. Soc.
Jpn. 1988, 61, 1291–1297; (b) Kaji, E.; Osa, Y.; Takahashi, K.; Hirooka, M.; Zen,
S.; Lichtenthaler, F. W. Bull. Chem. Soc. Jpn. 1994, 67, 1130–1140; (c) Kaji, E.;
Anabuki, N.; Zen, S. Chem. Pharm. Bull. 1995, 43, 1441–1447; (d) Kaji, E.;
Lichtenthaler, F. W.; Osa, Y.; Takahashi, K.; Zen, S. Chem. Pharm. Bull. 1996, 44,
437–440; (e) Kaji, E.; Osa, Y.; Shinohara, N.; Yanagi, C.; Semine, M.; Nishino, T.
Heterocycles 2004, 64, 317–331.
A mixture of 534 mg (1 mmol) benzoyloxime 12b and freshly
recrystallized NBS (356 mg, 2 mmol) in CCl4 (50 mL) was irradiated
with a 250 W heat lamp (Hg lamp) such that gentle reflux was ef-
fected. After 30 min the resulting solution was cooled (0 °C), the
succinimide was filtered off and evaporated to dryness. The residue
was solved in CH2Cl2 (200 mL) and washed with water (100 mL).
After drying (Na2SO4) the solvent was removed under reduced
pressure to give 13b (612 mg, quant.) as a hard foam; Rf = 0.60
(4:1 CCl4/EtOAc); ½a D20
ꢀ
+235.8 (c 1, CHCl3). 1H NMR (300 MHz,
CDCl3): 1.21, 1.22, 1.29 (3s, 27H, 3C(CH3)3), 4.26 (2H-m, 6-H2,
4.44 (ddd, 1H, H-5), 5.49 (dd, 1H, H-4), 6.21 (d, 1H, H-3), 7.41 (s,
1H, H-1), 7.48–8.11 (m, 5H, C6H5); J3,4 = J4,5 = 10.2, J5,6 = 3.6 and
2.5 Hz. 13C NMR (75.5 MHz, CDCl3): 27.2, 27.3 (C(CH3)3), 39.0,
39.1 (C(CH3)3), 60.9 (C-6), 66.6 (C-4), 67.9 (C-3), 73.2 (C-5), 73.8
(C-1), 128.0–134.2 (C6H5), 155.6 (C-2), 162.1 (COC6H5), 176.3,
177.4, 178.1 (tBuCO). MS (FD): m/z 611, 613 (M+).
15. Walczyna, R.; Smiatacz, Z.; Ciunik, Z. J. Carbohydr. Chem. 1993, 12, 1161–1171.
16. Ciunik, Z.; Walczyna, R.; Smiatacz, Z. J. Carbohydr. Chem. 1994, 13, 193–205.
17. (a) Theander, O. Acta Chem. Scand. 1958, 12, 1883–1885; (b) Ekborg, G.;
Lindberg, B.; Lönngren, J. Acta Chem. Scand. 1972, 26, 3287–3292; (c) Ekborg,
G.; Lönngren, J.; Svenson, S. Acta Chem. Scand. 1995, B29, 1031–1035; (d)
Kochetkov, N. K.; Dmitriev, B. A.; Chizhov, O. S.; Klimov, E. M.; Malysheva, N.
N.; Chernyak, A. Y.; Bayramova, N. E.; Torgov, V. I. Carbohydr. Res. 1975, 45,
283–290; (e) Shaban, M. A. E.; Jeanloz, R. W. Carbohydr. Res. 1976, 52, 115–127;
(f) Warren, C. D.; Augé, C.; Laver, M.; Suzuki, S.; Power, D.; Jeanloz, R. W.
Carbohydr. Res. 1980, 82, 71–83; (g) Augé, C.; Warren, C. D.; Jeanloz, R. W.; Kiso,
M.; Anderson, L. Carbohydr. Res. 1980, 82, 85–95; (h) Lee, H. H.; Congson, L. N.;
Whitfield, D. M.; Radies, L. R.; Krepinsky, J. J. Can. J. Chem. 1992, 70, 2607–2617;
(i) Kerékgyártó, J.; van der Ven, J. G. M.; Kamerling, J.; Lipták, A.; Vliegenthart, J.
F. G. Carbohydr. Res. 1993, 238, 135–145.
18. (a) Brimacombe, J. S.; How, M. J. J. Chem. Soc. (London) 1963, 3886–3887; (b)
Brimacombe, J. S.; Cook, M. C. J. Chem. Soc. (London) 1964, 2663–2666; (c)
Collins, P. M.; Overend, W. G. J. Chem. Soc. (London) 1965, 3448–3456.
19. (a) Collins, P. M. Chem. Commun. 1966, 164–165; (b) Barili, P. L.; Berti, G.;
Catalani, G.; D0Andrea, F.; Piccioni, L. J. Carbohydr. Chem. 2000, 19, 79–91.
20. Lichtenthaler, F. W.; Schneider-Adams, T. J. Org. Chem. 1994, 59, 6728–6734.
21. Cremer, D.; Pople, J. A. J. Am. Chem. Soc. 1975, 97, 1354–1358.
22. Jeffrey, G. A.; Yates, J. H. Carbohydr. Res. 1979, 74, 319–322.
23. Lergenmüller, M.; Lichtenthaler, F. W. Carbohydr. Res. 2007, 342, 2132–2137.
24. Lichtenthaler, F. W.; Schwidetzky, S.; Nakamura, K. Tetrahedron Lett. 1990, 31,
71–74.
5. Supplementary data
Crystallographic data, excluding structure factors, have been
deposited with the Cambridge Crystallographic Data Centre as sup-
plementary publication with CCDC No. 726514. Copies of the data
can be obtained free of charge on application with the Director,
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: +44 1223
336 033; e-mail: deposit@ccdc.cam.ac.uk).
Acknowledgement
25. IUPAC-IUB Joint Commission on conformational Nomenclature, Eur. J. Biochem.
1980, 111, 295–298.
26. Sheldrick, G. M. SHELXS-97. Program for the solution of crystal structures,
University of Göttingen, Germany, 1997.
Our thanks are due to Mrs. Sabine Foro for collecting the X-ray
data.
References
27. Sheldrick, G. M. SHELXL-97. Program for the refinement of crystal structures,
University of Göttingen, Germany, 1997.
28. Ohle, H.; Behrend, G. Ber. Dtsch. Chem. Ges. 1925, 58, 2585–2589. commercially
available from Aldrich Chem. Co..
29. Van Boeckel, C. A. A.; Beetz, T.; Kock-van-Dalen, A. C.; van Bekkum, H. Recl.
Trav. Chim. Pays-Bas 1987, 106, 596–598.
1. Jarglis, P.; Göckel, V.; Lichtenthaler, F. W. Tetrahedron: Asymmetry 2009, 20,
952–960.
2. (a) Lemieux, R. U.; James, K.; Nagabushan, T. L.; Ho, Y. Can. J. Chem. 1973, 51,
33–41; (b) Lemieux, R. U.; James, K.; Nagabushan, T. L. Can. J. Chem. 1973, 51,