2,3,4,6-Tetra-O-acetyl-α- d-gluco-pyranosyl azide

Article abstract of DOI:10.1107/S0108270108020702

The Cu^I-catalysed 1,3-dipolar cyclo-addition of an azide and a terminal alkyne is becoming an increasingly popular tool for synthetic chemists. This is the most representative of the so-called click reactions and it is used to generate 1,4-di-substituted triazoles in high yield. During studies on such cyclo-addition reactions, a reduced reactivity of an -glucosyl azide with respect to the corresponding Β-anomer was observed. With the aim of understanding this phenomenon, the structure of the title compound, C14H19N3O9, has been determined at 140 K. The glucopyranosyl ring appears in a regular ⁴ C 1 chair conformation with all the substituents in equatorial positions, except for the anomeric azide group, which adopts an axial orientation. The observed bond lengths are consistent with a strong anomeric effect, which is reflected in a change in dipolar character and hence reduced reactivity of the -glucosyl azide.

Full text of DOI:10.1107/S0108270108020702

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
2
005b; Nepogodiev et al., 2007). Initial studies were based on
the immediately accessible ꢁ-linked sugar azides, which do not
mirror the anomeric stereochemistry of starch. We report here
the structural analysis of the title compound, (I), prepared
according to Bianchi & Bernardi (2006). The X-ray structure
of the corresponding ꢁ-linked anomer, viz. 2,3,4,6-tetra-
O-acetyl-ꢁ-d-glucopyranosyl azide, (II), has already been
reported (Temelkoff et al., 2004).
ISSN 0108-2701
2,3,4,6-Tetra-O-acetyl-a-D-gluco-
pyranosyl azide
a
a
Simone Dedola, Sergey A. Nepogodiev, David L.
b
a
Hughes and Robert A. Field *
a
Department of Biological Chemistry, John Innes Centre, Colney Lane, Norwich
b
NR4 7UH, England, and School of Chemical Sciences and Pharmacy, University of
East Anglia, Norwich NR4 7TJ, England
Correspondence e-mail: rob.field@bbsrc.ac.uk
The six-membered pyranose ring in (I) adopts a chair
conformation, with all exocyclic substituents adopting an
equatorial arrangement, except for the anomeric azide which
has the expected axial orientation (Fig. 1). The geometry of
the pyranose ring and the orientation of the acetate groups of
Received 2 June 2008
Accepted 4 July 2008
Online 19 July 2008
I
The Cu -catalysed 1,3-dipolar cycloaddition of an azide and a
(
I) are very similar to those features in the corresponding
-anomer, (II) (Temelkoff et al., 2004). However, whereas the
terminal alkyne is becoming an increasingly popular tool for
synthetic chemists. This is the most representative of the so-
called ‘click reactions’ and it is used to generate 1,4-di-
substituted triazoles in high yield. During studies on such
cycloaddition reactions, a reduced reactivity of an ꢀ-glucosyl
azide with respect to the corresponding ꢁ-anomer was
observed. With the aim of understanding this phenomenon,
the structure of the title compound, C H N O , has been
ꢁ
length of the C1—O5 bond in (I) [1.423 (3) A] is the same
˚
˚
as in (II) [1.420 (2) A], the C1—N11 [1.510 (3) versus
˚ ˚
.460 (2) A] and C5—O5 [1.459 (3) versus 1.432 (2) A]
1
distances are significantly longer in (I) than in (II). As in (II),
the azide group in (I) appears as a nearly linear fragment
ꢀ
ꢀ
[
N11—N12—N13 = 173.0 (3) , compared with 171.4 (2) for
14
19
3
9
(
II)] and shows a very similar C1—N11—N12 bond angle
ꢀ
determined at 140 K. The glucopyranosyl ring appears in a
4
regular C chair conformation with all the substituents in
[
113.7 (2) versus 113.74 (14) for (II)].
However, the N—N bond lengths for the azide group and
1
equatorial positions, except for the anomeric azide group,
which adopts an axial orientation. The observed bond lengths
are consistent with a strong anomeric effect, which is reflected
in a change in dipolar character and hence reduced reactivity
of the ꢀ-glucosyl azide.
the C1—N11 distances in (I) and (II) are different. The
structural differences between the anomeric glucosyl azides
Comment
Glycosyl azides represent important and versatile building
blocks in carbohydrate chemistry (Gy o¨ rgyde a´ k & Thiem,
2006). They have been widely used as synthetic intermediates
for the preparation of glycosyl amines, asparagine-linked
glycopeptides (Herzner et al., 2000) and, more recently, tri-
azole-linked neoglycoconjugates (Dedola et al., 2007;
Dondoni, 2007). These last became available as a result of the
I
discovery of the highly efficient Cu -catalysed cycloaddition
reaction between azides and terminal alkynes (Rostovtsev et
al., 2002; Tornøe et al., 2002), which is commonly referred to as
‘
click chemistry’. This cycloaddition process has been exten-
sively used for the synthesis of a variety of neoglycoconjugates
Dedola et al., 2007; Dondoni, 2007). In the course of our work
(
on the synthesis of starch-like molecules, we experienced
major problems with stereocontrol in the synthesis of inter-
sugar chain glycosidic linkages (Marmuse et al., 2005a). We
therefore resorted to the preparation of pseudo-starch frag-
ments based on glucosyl triazole linkages (Marmuse et al.,
Figure 1
A view of the molecular structure of (I), showing the atom-numbering
scheme. For clarity, only the major component of the disordered
–CH OCOMe group at C6 is shown. Displacement ellipsoids are drawn
2
at the 50% probability level and H atoms are shown as capped sticks.
Acta Cryst. (2008). C64, o445–o446
doi:10.1107/S0108270108020702
# 2008 International Union of Crystallography o445

organic compounds
are all in keeping with the expected influence of the anomeric
effect (Briggs et al., 1984; Wolfe et al., 1979). For (II), the
˚
terminal N12—N13 bond [1.119 (3) A] is shorter than the
˚
N11—N12 bond [1.243 (2) A], whereas in (I), these are more
˚
similar in value [1.195 (4) and 1.165 (3) A, respectively]. One
C62/C72 was found to be common to both orientations and was
refined with full occupancy for that site using the EXYZ and EADP
restraints in SHELXL97 (Sheldrick, 2008). H atoms were included in
idealized positions, with C—H distances for the methyl, methylene
˚
and methine groups set at 0.96, 0.97 and 0.98 A, respectively, and with
U
iso(H) = 1.5Ueq(C) for the methyl group and 1.2Ueq(C) for the
might therefore anticipate a significant reactivity difference
between compounds (I) and (II) in dipolar cycloaddition
chemistry, which we have indeed observed: a much lower
reactivity of ꢀ-azide (I) compared with ꢁ-azide (II) is evident
remaining groups. The absolute configuration of the C atoms could
not be determined from the X-ray data; the assignment was based on
the known configuration of the starting material.
Data collection: CrysAlis CCD (Oxford Diffraction, 2007); cell
refinement: CrysAlis RED (Oxford Diffraction, 2006); data reduc-
tion: CrysAlis RED; program(s) used to solve structure: SHELXS97
(Sheldrick, 2008); program(s) used to refine structure: SHELXL97
(Sheldrick, 2008); molecular graphics: Mercury (Macrae et al., 2006);
software used to prepare material for publication: SHELXL97 and
publCIF (Westrip, 2008).
I
in the Cu -catalysed synthesis of triazoles. This is consistent
with other experimental observations (Wilkinson et al., 2006)
and in accord with computational studies, which show the
crucial role that a partial negative charge on atom N11 plays in
I
the mechanism of the Cu -catalysed cycloaddition of azides
and alkynes (Himo et al., 2005).
The authors are grateful to the BBSRC and the EPSRC for
financial support.
Experimental
2
,3,4,6-Tetra-O-acetyl-ꢀ-d-glucopyranosyl azide, (I), was prepared
1
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: BM3053). Services for accessing these data are
described at the back of the journal.
along with the ꢁ-anomer, (II), in a 9:1 ratio (determined by H NMR
spectroscopy) as described previously (Bianchi & Bernardi, 2006),
using tetra-O-acetyl-ꢁ-d-glucopyranosyl chloride (Korytnyk & Mills,
1
959) and Me
using purification by silica-gel column chromatography. Crystals of
I) suitable for X-ray diffraction analysis were obtained as colourless
3 3
SiN (Soli et al., 1999). Single isomers were obtained
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C
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r
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Monoclinic, P21
Mo Kꢀ radiation
˚
a = 10.806 (4) A
À1
ꢂ = 0.12 mm
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˚
b = 7.9840 (13) A
˚
c = 11.0107 (8) A
0.45 Â 0.43 Â 0.30 mm
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ꢁ
= 109.742 (2)
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diffractometer
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(CrysAlis RED; Oxford
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int = 0.039
(
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2
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2
R[F > 2ꢃ(F )] = 0.039
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À3
2
˚
Áꢄmax = 0.15 e A
˚
À3
Áꢄmin = À0.16 e A
3125 reflections
257 parameters
1 restraint
Absolute structure: Flack (1983),
with 1440 Friedel pairs
Flack parameter: 0.6 (12)
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ꢁ
o446 Dedola et al.
C
14
H N O
19 3 9
Acta Cryst. (2008). C64, o445–o446