Enantioselective catalysis. Part 142: Carbohydrate-derived oxime ethers from functionalised aldehydes and O-β-D-glucopyranosylhydroxylamine - New C=N ligands stable towards hydrolysis

Article abstract of DOI:10.1016/S0957-4166(01)00451-7

A new way of linking carbohydrates to phosphorus- or nitrogen-containing aldehydes via oxime ethers is described resulting in novel C=N ligands which are stable towards hydrolysis. Reaction of O-β-D-glucopyranosylhydroxylamine 2 with 2-diphenylphosphanylbenzaldehyde 3 or pyridine-2-carbaldehyde 4 afforded the oxime ethers O-(β-D-glucopyranosyl)-2-diphenylphosphanylbenzaldoxime 5 and O-(β-D-glucopyranosyl)pyridine-2-carbaldoxime 6. After peracetylation of the hydroxyl groups in 5 and 6, the protected sugar derivatives O-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-2- diphenylphosphanylbenzaldoxime 7 and O-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)pyridine-2-carbaldoxime 8 were obtained. The molecular structure of 7 was established by X-ray diffraction studies.

Full text of DOI:10.1016/S0957-4166(01)00451-7

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 2671–2675
Enantioselective catalysis. Part 142: Carbohydrate-derived oxime
ethers from functionalised aldehydes and
O-b-
D
-glucopyranosylhydroxylamine—new CꢀN ligands stable
towards hydrolysis†
Henri Brunner,* Maximilian Scho¨nherr and Manfred Zabel‡
Institut fu¨r Anorganische Chemie, Universita¨t Regensburg, D-93040 Regensburg, Germany
Received 10 September 2001; accepted 15 October 2001
Abstract—A new way of linking carbohydrates to phosphorus- or nitrogen-containing aldehydes via oxime ethers is described
resulting in novel CꢀN ligands which are stable towards hydrolysis. Reaction of O-b- -glucopyranosylhydroxylamine 2 with
2-diphenylphosphanylbenzaldehyde 3 or pyridine-2-carbaldehyde 4 afforded the oxime ethers O-(b- -glucopyranosyl)-2-
diphenylphosphanylbenzaldoxime 5 and O-(b- -glucopyranosyl)pyridine-2-carbaldoxime 6. After peracetylation of the hydroxyl
groups in 5 and 6, the protected sugar derivatives O-(2,3,4,6-tetra-O-acetyl-b- -glucopyranosyl)-2-diphenylphosphanylbenz-
aldoxime 7 and O-(2,3,4,6-tetra-O-acetyl-b- -glucopyranosyl)pyridine-2-carbaldoxime 8 were obtained. The molecular structure
of 7 was established by X-ray diffraction studies. © 2001 Elsevier Science Ltd. All rights reserved.
D
D
D
D
D
1. Introduction
and have been successfully implemented in different
ligand concepts, e.g. imines from the condensation of
primary amines with carbonyl compounds have been
successfully used in transition-metal catalysed reac-
tions.2 A limiting factor for these products is their
susceptibility to hydrolysis which often prevents chro-
matographic purification, further derivatisation or the
use of aqueous solvents. The tendency for hydrolysis is
high for imines, it is reduced for hydrazones and much
lower for oximes. In fact, oxime ethers are very stable
towards hydrolytic conditions (Fig. 1).
The most effective non-enzymatic approach towards
asymmetric catalysis is the use of chiral metal com-
plexes as catalysts.1 This approach requires chiral lig-
ands that bind to the metal during the catalytic cycle,
multiplying their chiral information throughout the
reaction by transfer to the substrate. The availability of
chiral building blocks for ligand synthesis is an impor-
tant factor. Compounds from the chiral pool such as
carbohydrates and amino acids meet these requirements
C
N
O
N
C
N
N
>
>
C
C
oximes
hydrazones
imines
Figure 1. Carbonyl derivatives and their tendency towards hydrolysis.
* Corresponding author. Fax: +49-(0)941/943-4439; e-mail: henri.brunner@chemie.uni-regensburg.de
† For Part 141, see: Brunner, H.; Niemetz, M. Chem. Monthly, in press.
‡ X-Ray structure analysis.
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00451-7

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H. Brunner et al. / Tetrahedron: Asymmetry 12 (2001) 2671–2675
Our new approach is the connection of carbohydrate
derivatives and phosphorus- or nitrogen-ligands via
oxime ethers. The acid-catalysed condensation of alde-
hydes and hydroxylaminoglycosides can be carried out
in the presence of water, yielding products resistant to
hydrolysis over a wide pH range. Herein, an enantio-
pure building block from the chiral pool is introduced
into the ligand which, due to its many functional
groups, may bind additives and orient substrates prior
to the actual catalysis. Another aspect is the ready
protection of the sugar’s hydrophilic hydroxyl groups
by acetylation or benzoylation resulting in lypophilic
esters soluble in organic solvents.
dissolve the phosphine 3. The progress of the condensa-
tion was monitored by TLC and the reaction was found
to be complete after 24 h. Removal of the solvent and
subsequent chromatography on silica gel afforded pure
5 as a white solid in almost quantitative yield. 5 is
soluble in most organic solvents but not in water. The
31P{1H} NMR spectrum showed only one signal at
−14.98 ppm indicating that no phosphine oxide was
formed during the reaction or the work-up.
In a similar reaction, pyridine-2-carbaldehyde 4 gave
O-(b-D-glucopyranosyl)pyridine-2-carbaldoxime 6 in
very good yield (Scheme 2). Since aldehyde 4 is soluble
in water, THF was not needed as a co-solvent. Work-
up as for 5 yielded 6 as a white hygroscopic powder
soluble in water and methanol.
2. Results and discussion
O-b- -Glucopyranosylhydroxylamine 2 was prepared
D
Both oxime ethers 5 and 6 were esterified with acetic
anhydride in pyridine, resulting in the peracetylated
oxime ethers 7 and 8 (Scheme 3). After aqueous work-
up and recrystallisation from hexanes/ethyl acetate, 8
was obtained as white needles, while 7 formed colour-
less crystals suitable for X-ray diffraction analysis. The
1H NMR spectra of 7 and 8 exhibited almost identical
chemical shifts and multiplet structures of the hydrogen
atoms in the sugar moiety. The imine analogue of 8 is
reported in the literature.4
by a modification of the method published for the
synthesis of its galactose analogue.3 When O-(2,3,4,6-
tetra-O-acetyl-b-
imide 1 was treated with an excess of hydrazine hydrate
-glucopyranosylhydroxylamine 2
D-glucopyranosyl)-N-hydroxysuccin-
in methanol, O-b-
D
was obtained after recrystallisation from methanol in
58% yield (Scheme 1).
Condensation of 2 with 2-diphenylphosphanylbenzalde-
hyde 3 under acidic conditions using 0.1 equiv. HCl
and a mixture of water/THF as the solvent gave O-(b-
Fig. 2 shows the molecular structure of 7. The CꢀN
double bond has trans-configuration with a torsion
D
-glucopyranosyl)-2-diphenylphosphanylbenzaldoxime
5 (Scheme 2). THF as a co-solvent was needed to
OH
OAc
O
7 equiv. N2H4 H2O
MeOH, r.t., 48 h, 58%
O
O
AcO
AcO
HO
HO
O N
O
NH2
OH
AcO
O
2
1
Scheme 1.
OH
P
P
O
HO
HO
O
N
O
3
OH
5
OH
O
HO
HO
O
NH2
OH
2
OH
N
O
O
HO
HO
N
O
N
4
OH
6
Scheme 2.

H. Brunner et al. / Tetrahedron: Asymmetry 12 (2001) 2671–2675
2673
OAc
OAc
O
P
O
AcO
AcO
N
AcO
AcO
O
N
O
N
OAc
OAc
8
7
Scheme 3.
Figure 2. Molecular structure of 7.
angle O(1)ꢁN(1)ꢁC(19)ꢁC(18) of 177.11(1)°. The tor-
sion angle N(1)ꢁC(19)ꢁC(18)ꢁC(17) is 29,79(1)° indicat-
ing that the CꢀN double bond is inclined with respect
the new ligands in asymmetric transition-metal catalysis
is currently in progress.
,
to the adjacent phenyl ring. With 1.476(2) A the bond
C(19)ꢁC(18) is a single bond open for rotation to allow
bidentate metal-binding through both the phosphorus
and the nitrogen atom. The substituents of the
pyranose ring are all in equatorial positions confirming
the configurational stability of the sugar moiety
throughout the reaction sequence.
4. Experimental
4.1. General remarks
1H NMR (i-TMS): Bruker AC 250 and ARX 400, 31P
NMR (ext. 85% H3PO4): Bruker ARX 400. Melting
points: Bu¨chi SMP-20. Optical rotations: Perkin–Elmer
polarimeter 241. Mass spectra: Varian MAT 95. Com-
pound 3 was prepared according to the literature.5
3. Conclusion
4.2. O-b-D-Glucopyranosylhydroxylamine 2
A synthesis of new chiral water-stable CꢀN ligands has
been established by linking hydroxylamino–carbohy-
drates to aldehydes via oxime ether substructures. By
reaction of 5 and 6 with acetic anhydride, the peracety-
lated oxime ethers 7 and 8 were obtained. Compound 7
could be examined by X-ray diffraction analysis. The
method described allows the use of varying aldehydes
and a manifold of sugars. Analysis of the efficiency of
To suspension of O-(2,3,4,6-tetra-O-acetyl-b-D-
a
glucopyranosyl)-N-hydroxysuccinimide 1 (10 g, 22.5
mmol) in methanol (400 mL) was added hydrazine
hydrate (7 mL, 157 mmol) and the mixture was stirred
at room temperature for 48 h. The precipitated butane-
dioic acid dihydrazide was filtered off and the solution
was cooled to −18°C for 10 h affording pure crystalline

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H. Brunner et al. / Tetrahedron: Asymmetry 12 (2001) 2671–2675
1
2 (2.53 g, 57%). Mp 182°C; [h]2D5=−40.0 (c 1, H2O); H
NMR (250 MHz, D2O): l=3.17 (dd, 1H, J2,1=8.2 Hz,
(2 mL). Acetic anhydride (191 ml, 206 mg, 2 mmol) was
added and the solution was stirred for 16 h at 60°C.
The reaction mixture was poured on ice water (50 mL)
and 20% HCl (10 mL), extracted with CH2Cl2 (3×20
mL) and the combined organic extracts were dried over
MgSO4. Removal of the solvent under reduced pressure
and subsequent chromatography on silica gel eluting
with EtOAc/hexanes 2:1 gave pure 7 as a white solid in
89% yield. Colourless crystals suitable for X-ray dif-
fraction analysis were obtained after recrystallisation
from hexanes/EtOAc. Mp 77°C; [h]2D5=−17.3 (c 3,
J
2,3=9.2 Hz, H-2), 3.24 (dd, 1H, J4,3=8.7 Hz, J4,5=9.6
Hz, H-4), 3.35 (ddd, 1H, J5,6a=2.2 Hz, J5,6b=5.7 Hz,
5,4=9.6 Hz, H-5), 3.38 (dd, 1H, J3,4=8.7 Hz, J3,2=9.2
J
Hz, H-3), 3.60 (dd, 1H, J6b,5=5.7 Hz, J6b,6a=12.3 Hz,
H-6b), 3.81 (dd, 1H, J6a,5=2.2 Hz, J6a,6b=12.3 Hz,
H-6a), 4.44 (d, 1H, J1,2=8.2 Hz, H-1); MS (ESI,
MeOH+1% AcOH): m/z=196.2 (MH+, 100); anal.
calcd for C6H13NO6 (195.2): C, 36.92; H, 6.17; N, 7.18.
Found: C, 36.86; H, 6.94; N, 7.38%.
1
CH2Cl2); H NMR (400 MHz, CDCl3): l=1.97 (s, 3H,
4.3. O-(b-
D
-Glucopyranosyl)-2-diphenylphosphanylbenz-
CH3), 2.01 (s, 3H, CH3), 2.03 (s, 3H, CH3), 2.07 (s, 3H,
aldoxime 5
CH3), 3.74 (ddd, 1H, J5,4=9.9 Hz, J5,6a=4.2 Hz, J5,6b
=
=
2.2 Hz, Hgluc-5), 4.08 (dd, 1H, J6b,6a=12.4 Hz, J6b,5
To a solution of 2 (195 mg, 1 mmol) and 2-
diphenylphosphanylbenzaldehyde 3 (290 mg, 1 mmol)
in H2O (20 mL) and THF (20 mL) was added 0.1 M
HCl (1 mL) and the reaction mixture was stirred at
room temperature for 24 h. After removal of the sol-
vents under reduced pressure the residue was taken up
in CH2Cl2 (50 mL), washed with water (2×20 mL) and
brine (1×10 mL) and purified by column chromatogra-
phy on silica gel using CH2Cl2/methanol 12:1 to give
pure 5 as a white solid in 95% yield. Mp 145°C;
[h]2D5=−1.8 (c 3, CH2Cl2); 1H NMR (400 MHz, DMSO-
d6): l=3.05–3.25 (m, 4H, Hgluc), 3.40–3.48 (m, 1H,
Hgluc), 3.57–3.65 (m, 1H, Hgluc), 4.50–4.44 (m, 1H,
2.2 Hz, Hgluc-6b), 4.30 (dd, 1H, J6a,6b=12.4 Hz,
6a,5=4.2 Hz, Hgluc-6a), 5.10–5.27 (m, 4H, Hgluc), 6.90–
J
6.95 (m, 1H, Har), 7.19–7.25 (m, 4H, Har), 7.27–7.40 (m,
8H, Har), 7.83–7.88 (m, 1H, Har), 8.83 (d, 1H, JP=4.4
Hz, CHꢀN); 31P{1H} NMR (400 MHz, CDCl3): l=
−13.94; MS (CI-MS): m/z=288.2 (100), 366.3 (12),
636.3 (MH+, 3); anal. calcd for C33H34NO10P (635.6):
C, 62.36; H, 5.39; N, 2.20. Found: C, 62.10; H, 5.62; N,
2.09%.
4.6. O-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-
pyridine-2-carbaldoxime 8
H
gluc), 4.83 (d, 1H, 3J=8.3 Hz, OH), 4.97 (d, 1H,
Reaction procedure as for 7 with O-(b-D-glucopyran-
J=5.0 Hz, OH), 5.06 (d, 1H, J=4.8 Hz, OH), 5.32 (d,
1H, J=5.2 Hz, OH), 6.81–6.86 (m, 1H, Har), 7.15–7.22
(m, 4H, Har), 7.38–7.44 (m, 7H, Har), 7.44–7.49 (m, 1H,
Har), 7.85–7.89 (m, 1H, Har), 8.74 (d, 1H, JP=4.4 Hz,
CHꢀN); 31P{1H} NMR (400 MHz, CDCl3): l=−14.98;
MS (FAB): m/z=288.2 (100), 468.5 (MH+, 49); anal.
calcd for C25H26NO6P (467.5): C, 64.24; H, 5.61; N,
3.00. Found: C, 64.01; H, 5.82; N, 2.81%.
osyl)pyridine-2-carbaldoxime 6 (107 mg, 0.43 mmol)
gave 8 as colourless needles in almost quantitative
1
yield. Mp 117°C; [h]2D5=−22.0 (c 2, CH2Cl2); H NMR
(250 MHz): l=2.03 (s, 3H, CH3), 2.04 (s, 3H, CH3),
2.05 (s, 3H, CH3), 2.08 (s, 3H, CH3), 3.85 (ddd, 1H,
J
5,4=9.8 Hz, J5,6a=4.3 Hz, J5,6b=2.4 Hz, Hgluc-5), 4.15
(dd, 1H, J6b,6a=12.4 Hz, J6b,5=2.4 Hz, Hgluc-6b), 4.33
(dd, 1H, J6a,6b=12.4 Hz, J6a,5=4.3 Hz, Hgluc-6a), 5.13–
5.39 (m, 4H, Hgluc), 7.31 (ddd, 1H, J2,3=6.5 Hz, J2,1
4.9 Hz, J2,4=2.3 Hz, Hpy-2), 7.72 (ddd, 1H, J3,4=7.9
Hz, J3,2=6.7 Hz, J3,1=1.7 Hz, Hpy-3), 7.76 (ddd, 1H,
=
4.4. O-(b-D-Glucopyranosyl)pyridine-2-carbaldoxime 6
Obtained as above from pyridine-2-carbaldehyde 4 and
2 without using THF as a co-solvent and after chro-
matography on silica gel using EtOAc/methanol 7:3 to
give pure 6 as a white hygroscopic powder in 92% yield.
J
4,3=7.9 Hz, J4,2=2.3 Hz, J4,1=1.0 Hz, Hpy-4), 8.27 (s,
1H, CHꢀN), 8.65 (ddd, 1H, J1,2=4.9, J1,3=1.7, J1,4
=
1.0, Hpy-1); MS (CI-MS): m/z=107.0 (100), 246.1 (23),
453.2 (MH+, 41); anal. calcd for C20H24N2O10 (452.4):
C, 53.10; H, 5.35; N, 6.19. Found: C, 53.10; H, 5.39; N,
6.20%.
1
Mp 76°C; [h]2D5=−16.3 (c 2, CH3OH); H NMR (250
MHz, D2O): l=3.30–3.43 (m, 1H, Hgluc), 3.44–3.55 (m,
3H, Hgluc), 3.63 (dd, 1H, J6a,6b=12.3 Hz, J=5.8 Hz,
H
gluc-6a), 3.82 (dd, 1H, J6b,6a=12.3 Hz, J=2.14, Hgluc-
6b), 5.07–5.12 (m, 1H, Hgluc), 7.39 (ddd, 1H, J2,3=7.6
Hz, J2,1=5.0 Hz, J2,4=1.3 Hz, Hpy-2), 7.68 (ddd, 1H,
4.7. Crystal data for compound 7
J
4,3=7.9 Hz, J4,2=1.3 Hz, J4,1=0.9 Hz, Hpy-4), 7.81
C33H34NO10P 7: colourless thin rod from EtOAc/
hexanes, Fw=635.58, monoclinic, space group P21 (no.
(ddd, 1H, J3,4=7.9 Hz, J3,2=7.6 Hz, J3,1=1.7 Hz,
Hpy-3), 8.29 (s, 1H, CHꢀN), 8.45 (ddd, 1H, J1,2=5.0
Hz, J1,3=1.7 Hz, J1,4=0.9 Hz, Hpy-1); MS (CI-MS):
m/z=107.0 (100), 122.0 (48), 285.2 (MH+, 4); anal.
calcd for C12H16O6N2 (284.3): C, 50.70; H, 5.67; N,
9.85. Found: C, 50.43; H, 5.78; N, 9.65%.
,
4), a=14.300(1), b=7.6003(5), c=15.008(1) A, i=
3
−3
,
96.135(9)°, V=1621.8(2) A , Z=2, Dx=1.301 Mg m ,
v(Mo-Ka)=0.142 mm−1, crystal dimensions 0.46×0
.20×0.08 mm3, u=0.71073
,
A (Mo-Ka radiation,
graphite monochromator, STOE Imaging Plate Diffrac-
tion System). Data collection at T=173 K, 1.87<q<
25.73°, h −17“17, k −9“9, l −18“18, 16306 reflections
measured, 6134 unique, merging Rint=0.0486). The
structure was solved by direct methods (SIR-976) and
refined by full-matrix least-squares based on F2
(SHELXL-977) with weights w=1/[|2(Fo)2+(0.0723P)2],
4.5. O-(2,3,4,6-Tetra-O-acetyl-b-
diphenylphosphanylbenzaldoxime 7
D-glucopyranosyl)-2-
O-(b-
D-Glucopyranosyl)-2-diphenylphosphanylbenzald-
oxime 5 (200 mg, 0.43 mmol) was dissolved in pyridine

H. Brunner et al. / Tetrahedron: Asymmetry 12 (2001) 2671–2675
2675
2
2
where P=(Fo +2Fc )/3. The H atoms were calculated
geometrically and a riding model was used during the
refinement process. The final consistency indexes for
all data were R1=0.0693 and wR2=0.1184, goodness-
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