Towards C-2 symmetrical macrocyles with an incorporated sucrose unit

Article abstract of DOI:10.1139/V06-035

The first C₂ symmetrical macrocyclic receptor containing two sucrose molecules has been prepared, albeit in low yield, by reaction of hexa-O-benzyl-6′-O-acroyl-6-O-allylsucrose in the presence of a second generation Grubbs catalyst (1,3-dimesit

Full text of DOI:10.1139/V06-035

492
Towards C-2 symmetrical macrocyles with an
incorporated sucrose unit1
S»awomir Jarosz and Arkadiusz Listkowski
Abstract: The first C2 symmetrical macrocyclic receptor containing two sucrose molecules has been prepared, albeit in
low yield, by reaction of hexa-O-benzyl-6′-O-acroyl-6-O-allylsucrose in the presence of a second generation Grubbs
catalyst (1,3-dimesityl-4,5-dihydroimidazol-2-ylidene ruthenium alkylidene complex). Highly selective protection of the
6′-OH group in 1′,2,3,3′,4,4′-hexa-O-benzylsucrose was a key step in the preparation of the precursor used under ring
closing metathesis (RCM) conditions.
Key words: sucrose, macrocyclic receptors, metathesis, regioselective transformations.
Résumé : La réaction du hexa-O-benzyl-6′-O-acroyl-6-O-allylsucrose en présence du catalyseur de Grubbs de
deuxième génération (complexe alkylidène 1,3-dimésityl-4,5-dihydroimidazol-2-ylidène ruthénium) nous a permis de
préparer, avec un faible rendement, le premier récepteur macrocyclique de symétrie C2 contenant deux molécules de su-
crose. La protection hautement sélective du groupe OH en 6′ du 1′,2,3,3′,4,4′-hexa-O-benzylsucrose est l’étape clé dans
la préparation du précurseur utilisé dans les conditions de fermeture de cycle par métathèse (RCM).
Mots clés : sucrose, récepteurs macrocycliques, métathèse, transformations régiosélectives.
[Traduit par la Rédaction] Jarosz and Listkowski 496
Introduction
pared another useful sucrose diol, compound 3 (8), and ap-
plied it in the preparation of a variety of crown ether analogs
(4, Fig. 1) (9).
In this paper a methodology leading to complex sucrose
macrocycles possessing higher symmetry will be described.
Differentiation of the primary hydroxyl groups in 3 is re-
quired for regioselective introduction of the proper olefinic
fragments needed for cyclization under ring closing metathe-
sis (RCM) conditions.
Sucrose, a cheap raw material, is available in more than
130 million tons per year; most of it is consumed on the
food market. This chemical is very demanding to work with
because of its very poor solubility in organic solvents (ex-
cept DMF, pyridine, and DMSO), presence of eight hydroxyl
groups that are difficult to differentiate, and the high sensi-
tivity of the glycosidic bond in acidic media. However, this
disaccharide is a subject of interest for several laboratories,
which use it as a starting material for the preparation of fine
chemicals (1–3), as well as biodegradable polymers or sur-
factants (4). Recently, a biocatalytic approach to sucrose
analogs has been published (5).
Synthesis of selectively protected
derivatives of hexa-O-benzylsucrose
Reaction of the free sucrose with 1 equiv. of silylating
agent preferentially protects the 6′-OH group (10). Since the
same feature applies for diol 2 (7), similar selective protec-
tion of 3 was also expected. Diol 3 was reacted with tert-
butyldimethylsilyl chloride to afford alcohol 5 in 48% yield.
Protection at the C-6′ position was confirmed by advanced
NMR experiments performed on derivative 7 in which the
COSY correlations between H-5 (glucose part) and both
olefinic protons were visible. Since the yield of product 5
was not particularly impressive, we used the more bulky
silyl reagent, tert-butyldiphenylsilyl chloride, and obtained
alcohol 6 in 60% yield. Its structure was also confirmed by
the NMR experiments performed on methyl uronate (11);
the significant lowfield shift of the H-5 resonance
(δ 4.56 ppm) proved that this proton is in close vicinity to
the ester group, hence the 6-OH (and not 6′-OH) group in
alcohol 7 was not protected (Scheme 1).
As part of an on-going program, we elaborated a conve-
nient route to 2,3,3′,4,4′-penta-O-benzylsucrose (6) (1), a
useful starting material for the preparation of derivatives
modified at the terminal (C1′, C6, C6′) positions. Differenti-
ation of the primary hydroxyl groups in 1 is possible, which
allows for the production of all three monoalcohols, as well
as the 6,6′-diol 2, in good yields (3, 7). Recently, we pre-
Received 30 August 2005. Published on the NRC Research
Press Web site at http://canjchem.nrc.ca on 6 April 2006.
Dedicated to Professor Walter Szarek on the occasion of his
65th birthday.
S. Jarosz2 and A. Listkowski. Institute of Organic
Chemistry, Academy of Sciences, 01-224 Kasprzaka 44/52,
Warsaw, Poland.
1This article is part of a Special Issue dedicated to Professor
Walter A. Szarek.
Synthesis of 6-O-allyl-6′-O-acroyl derivative 10, the di-
rect precursor of the C2-symmetrical macrocycle, was
achieved in 37% overall yield from 6 by allylation of the 6-
2Corresponding author (e-mail: sljar@icho.edu.pl).
Can. J. Chem. 84: 492–496 (2006)
doi:10.1139/V06-035
© 2006 NRC Canada

Jarosz and Listkowski
493
Fig. 1. Preparation of partially protected sucrose derivatives and
Scheme 1. (i) CH2Cl2, TBDMSCl (1 equiv.), DIPEA, DMAP,
synthesis of the crown ether analogs containing sucrose.
48%; (ii) CH2Cl2, TBDPSCl (1 equiv.), DIPEA, DMAP, 60%;
(iii) 1. Swern oxidation; 2. Ph3P=CH-CO2Me; (iv) CH2Cl2, 50%
NaOH, AlIBr, Bu4NBr, rt, 66%; (v) Bu4NF, THF, rt, 74%;
(vi) CH2Cl2, Et3N, DMAP, acroyl chloride, 75%; (vii) 1. Swern
oxidation; 2. Jones oxidation; 3. CH2N2, 64% overall.
Sucrose
20% overall
of 1
48%
ref. 8
overall
ref. 7
OH
HO
6
OH
6'
HO
MeO2C
BnO
3
6
i. or ii.
7
6'
O
TBDMSO
1'
O
RO
BnO
6
O
RO
1'
OH
O
BnO
BnO
O
OBn
O
O
5
BnO
O
BnO
BnO
O
OBn
3
OBn
OBn
O
O
BnO
BnO
OBn
O
OBn
OBn
BnO
OBn
OBn
7
1 R = H
2 R = BOM
OBn
BnO
OBn
iii.
OBn
COSY H5-H6, H5-H7
O
O
5. R = TBDMS (48%)
6. R = TBDPS (60%)
vii.
For differentiation between
the primary hydroxyl
groups in 1 see ref. ...
BnO
O
O
δ / 4.05 ppm
δ / 4.56 ppm
iv.
O
4
TBDPSO
O
O
RO
MeO
6
6'
BnO
H
H
O
O
OH group with allyl bromide,3 followed by removal of the
silyl protection from the 6′-OH and subsequent acroylation
(Scheme 1).
BnO
5
OBn
O
8. R = TBDPS
9. R = H
10. R = -C(O)-CH=CH2
v.
BnO
OBn
11
vi.
OBn
Cyclization of sucrose derivative 11 to the C2-
symmetrical receptor
three olefinic carbon resonances (at δ 131.1 (=CH2), 129.4,
and ~128.2 ppm, respectively; assigned from the HETCOR
correlations), one carbonyl resonance (at δ 165.9 ppm), and
one set of signals connected with the sucrose skeleton (rep-
resentative resonances at δ 104.7 (C-2′) and 90.3 (C-1))
were seen, which pointed at structure 15. The geometry
across the newly created double bond is most likely E (as-
sumption based on the literature examples (12)), but because
of the symmetry of 15, it cannot be assigned by NMR.
We plan to assign this geometry by desymmetrization of
the molecule; the results will be reported in a separate paper.
Reaction of 11 performed in the presence of a second gen-
eration Grubbs catalyst (1,3-dimesityl-4,5-dihydroimidazol-
2-ylidene ruthenium alkylidene complex (11)) afforded a
mixture of products in a total yield of about 35%. Four dif-
ferent compounds (12–15) were isolated by HPLC
(Scheme 2).
Structures of all these products were established by MS
and high-resolution NMR spectroscopy. The MS spectra of
compounds 12 and 13 clearly pointed at the presence of only
one molecule of sucrose (in both spectra, the signals m/z 971
[M(C58H60O12) + Na+] and 987 [M(C58H60O12) + K+] were
seen). The geometry across the newly created double bonds
was determined from the 1H NMR spectra of these
macrocycles. Thus, the large coupling constant (J = 16.1 Hz)
pointed at the E geometry in 12, while the smaller constant
(J = 12.0 Hz) proved the Z geometry in 13.
The MS data of one of the two remaining derivatives were
in accordance with the dimeric structure; the signal at m/z
1919 [(C116H120O24) + Na+] could be assigned to the ex-
pected cyclic derivative 14. In the 13C NMR spectrum of this
compound, only one -CH=CH-C(O)- group was seen
(δ 165.8, 145.6, and 120.0 ppm), which strongly supported
the symmetrical structure. Further information was obtained
from the 1H NMR spectrum; the large coupling constant (J =
15.8 Hz) among two olefinic protons (at δ 6.83 and
5.96 ppm) clearly pointed at the E geometry across this dou-
ble bond. This is consistent with the literature data reporting
on a preferential synthesis of the E isomers under such con-
ditions (12).
Conclusion
The first synthesis of a C2-symmetrical macrocycle con-
taining two sucrose units was realized by dimerization of the
6-O-allyl-6′-O-acroylsucrose monomer under RCM condi-
tions with Grubbs II catalyst (1,3-dimesityl-4,5-dihydro-
imidazol-2-ylidene ruthenium alkylidene complex). Besides
the expected receptor 14, two compounds (with E and Z ge-
ometry, respectively, across the newly created double bond)
resulting from the intramolecular cyclization and one
dimeric open-chain product (from reaction among two allyl
moieties) were produced. The overall yield of this process
was low (ca. 35%).
Experimental
General
NMR spectra were recorded with a Bruker AM 500 spec-
trometer for solutions in CDCl3 (internal Me4Si) unless oth-
erwise stated. Most of the resonances were assigned by
COSY (1H–1H) and (or) HETCOR and DEPT correlations.
In the MS spectrum of the last identified product, the sig-
nal at m/z 1947 (differing by 28 Da (2 × CH2 groups) from
the dimer 14) was detected. In the 13C NMR spectrum, only
3 Interestingly, the reaction with allyl chloride was not effective under PTC conditions; removal of the silyl block from the C-6′ end, followed
by allylation of both 6-OH and 6′-OH groups, led to known 6,6′-di-O-allyl-1′2,3,3′,4,4′-hexa-O-benzylsucrose (ref. 3).
© 2006 NRC Canada

494
Can. J. Chem. Vol. 84, 2006
Scheme 2. (i) CH2Cl2, second generation Grubbs catalyst, reflux, 3.5 h.
O
BnO
BnO
β
O
O
γ
OBn
δ
BnO
O
i.
O
O
BnO
α
O
OBn
OBn
O
O
O
+
O
O
1
BnO
O
5
5'
O
BnO
BnO
O
OBn
10
BnO
1'
O
OBn
OBn
OBn
OBn
O
OBn
OBn
O
Jα,β = 16.1 Hz
+
12
14
Jα,β = 15.8 Hz
O
β
O
α
β
BnO
OBn
OBn
OBn
γ
O
γ
O
O
δ
BnO
α
O
O
O
O
O
BnO
BnO
+
O
O
O
O
BnO
BnO
O
δ
OBn
OBn
O
O
O
OBn
OBn
φ
ε
OBn
OBn
BnO
OBn
BnO
15
13
Jα,β = 12.0 Hz
1
The H and 13C aromatic resonances occurring at the typical
δ values were omitted for simplicity. Mass spectra were re-
corded with an ESI/MS Mariner (PerSeptive Biosystem)
mass spectrometer. Optical rotations were measured with a
Jasco P-1020 polarimeter for solutions in CHCl3 (c = 1) at
room temperature (rt). IR spectra (film) were recorded with
a PerkinElmer Spectrum 2000 apparatus. Column chroma-
tography was performed on silica gel (Merck, 70–230 or
230–400 mesh). Methylene chloride was distilled from CaH2
and THF from potassium prior to use. Organic solutions
were dried over anhydrous sodium sulfate.
added at –78 °C within 5 min to a solution of a Swern re-
agent (generated from 0.1 mL of oxalyl chloride and 0.3 mL
DMSO in 5 mL of CH2Cl2). After stirring for 15 min at
–78 °C, triethylamine (0.3 mL) was added and the mixture
was allowed to attain rt. Water (3 mL) was added, the
organic layer was separated, dried, and concentrated. The
residue was dissolved in dry benzene (5 mL) to which
methoxycarbonyl methylenetriphenylphosphorane (50 mg)
was added; the mixture was stirred for 2 h at rt, filtered, and
concentrated. The crude product was purified by column
chromatography (hexane – ethyl acetate, 8:1) to afford ester
7 (67 mg, 0.064 mmol, 80%). IR (film, cm–1) υ: 2929, 2858,
1
1725, 1675, 1454, 1090, 1028, 736, 698. H NMR δ: 6.93
1′,2,3,3′,4,4′-Hexa-O-benzyl-6′-O-tert-butyldimethyl-
silylsucrose (5)
(dd, 1H, J5,6 = 4.4 Hz, J6,7 = 15.8 Hz, H-6), 6,04 (dd, 1H,
J5,7 = 1.8 Hz, H-7), 5.95 (d, 1H, J1,2 = 3.7 Hz, H-1), 4.46 (d,
1H, J3′,4′ = 7.5 Hz, H-3′), 4.33 (dd, 1H, J4′,5′ = 7.5 Hz, H-
4′), 3.96 (dd, 1H, J2,3 = 7.4 Hz, J3,4 = 8.9 Hz), 3.75 (s, 3H,
OCH3), 3.69 (d, 1H, J1′A,1′B = 10.9 Hz, H-1′A), 3.22 (dd,
1H, J1,2 = 10.1 Hz, H-4), 0,93 (s, 9H, CMe3), 0.10, 0.08
(2×s, SiMe2). 13C NMR δ: 166.7 (CO), 145.1 (C-6), 120.8
(C-7), 104.2 (C-2′), 88.8 (C-1), 83.8 (C-3′), 81.8 (C-4′),
81.7 (C-5′), 81.6 (C-4′), 81.0 (C-3), 79.9 (C-2), 75.6, 75.1,
73.4, 73.0, 72.7, 72.1 (6×CH2Ph), 71.7 (C-1′), 69.7 (C-5),
63.4 (C-6′), 51.4 (OCH3), 25.9 (CMe3), 18.3 (CMe3), –5.42,
–5.44 (SiMe2). MS m/z: 1073 [M(C63H74O12Si) + Na+].
To a solution of diol 3 (1.25 g, 1.4 mmol), DMAP
(0.12 g), and diisopropylethylamine (0.8 mL) in CH2Cl2
(50 mL), a solution of tert-butyldimethylsilyl chloride
(0.27 mL, 1.4 mmol) in CH2Cl2 (5 mL) was added over
60 min and the mixture was stirred for 24 h at rt. Water
(70 mL) was added, the organic phase was separated, and
the aqueous one extracted with ether (70 mL). The com-
bined organic solutions were dried, concentrated, and the
crude product was isolated by column chromatography
(hexane – ethyl acetate, 7:1 to 1:1) to give the title com-
pound (5) (0.48 g, 0.48 mmol, 48% calcd. on consumed 3)
as a colorless oil and unreacted alcohol 3 (0.36 g,
0.41 mmol). Data for 6: [α]D +33.5°. 1H NMR (200 MHz) δ:
5.97 (d, 1H, J1,2 = 3.8 Hz, H-1), 0.88 (s, 9H, 3×CCH3), 0.06,
0.05 (2×s, SiMe2). 13C NMR (50 MHz) δ: 104.3 (C-2′), 88.6
(C-1), 83.6, 81.9, 80.7, 80.6, 80.1, 77.8 and 71.2 (C-
2,3,3′,4,4′,5,5′), 75.6, 74.9, 73.5, 73.1, 72.6, 72.0, 71.8, and
62.9, 62.0 (C-1′,6,6′, 6×OCH2Ph), 25.9 (CMe3), 18.3 (CMe3),
–5.0 (SiMe2). MS m/z: 1019 [M(C60H72O11Si) + Na+]. Anal.
calcd. for C60H72O11Si: C 72.26, H 7.28; found: C 72.0, H 7.4.
1′,2,3,3′,4,4′-Hexa-O-benzyl-6′-O-tert-butyldiphenylsilyl-
sucrose (6)
To a solution of diol 3 (1.23 g, 1.39 mmol), DMAP
(78 mg, 0.64 mmol), and diisopropylethylamine (0.5 mL) in
CH2Cl2 (50 mL), tert-butyldiphenylsilyl chloride (0.36 mL,
1.4 mmol) was added over 30 min and the mixture was
stirred overnight at rt. Water (70 mL) was added, the organic
phase was separated, and the aqueous one extracted with
CH2Cl2 (30 mL). The combined organic solutions were
dried, concentrated, and the crude product was isolated by
column chromatography (hexane – ethyl acetate, 5:1) to give
the title compound (6) (0.93 g, 0.829 mmol, 60%) as a col-
Determination of the structure of 5 — Synthesis of the
␣,␤-unsaturated ester 7
Alcohol 5 (80 mg, 0.08 mmol) in CH2Cl2 (2 mL) was
© 2006 NRC Canada

Jarosz and Listkowski
495
orless oil. [α]D +26.2°. IR (film, cm–1) υ: 2930, 2859, 1497,
hexa-O-benzyl-6′-O-tert-butyl-diphenylsilylsucrose (8) (0.91 g,
0.782 mmol, 52%; 66% calcd. on consumed 6) as a colorless
oil and unreacted alcohol 6 (0.38 g, 0.339 mmol). [α]D
+24.8°. IR (film, cm–1) υ: 2929, 2859, 1453, 1090, 1027,
737, 698. MS m/z: 1184.6 [M(C73H80O11Si) + Na+].
When the allyl bromide was replaced with allyl chloride,
removal of the silyl protection from the C-6′ position was
noted and the diallylated product was isolated from the reac-
tion mixture in good yield.
1
1454, 1089, 1028, 737, 698. H NMR δ: 5.90 (d, J1,2
=
3.8 Hz, 1H, H-1), 1.06 (s, 9H, CMe3). 13C NMR δ: 104.2
(C-2′), 88.7 (C-1), 83.6, 81.9, 80.7, 80.5, 80.1, 77.7, 71.3
(C-2,3,3′,4,4′,5,5′), 75.5, 74.9, 73.4, 73.1, 72.7, 72.3, 72.1
(C-1′ and 6×CH2Ph), 63.9, 61.8 (C-6 and C-6′), 26.9 (Me3C-
Si), 19.2 (Me3CSi). MS m/z: 1143.6 [M(C70H76O11Si) +
Na+]. Anal. calcd. for C70H76O11Si: C 74.97, H 6.83; found:
C 74.6, H 6.9.
To a solution of 8 (0.91 g, 0.782 mmol) in THF (20 mL),
Bu4NF·3H2O (0.32 g, 1.0 mmol) was added and the mixture
was stirred overnight at rt. The solvent was removed under
reduced pressure and the residue was partitioned between
ethyl acetate (40 mL) and water (40 mL). The organic layer
was separated, dried, concentrated, and the residue was puri-
fied by column chromatography (hexane – ethyl acetate, 3:1
to 2:1) to give alcohol 9 (0.54 g, 0.58 mmol, 74%) as a col-
orless oil. [α]D +35.2°. IR (film, cm–1) υ: 2917, 2867, 1496,
(5S)-2,3,4-Tri-O-benzyl-5-C-metoxycarbonyl-␣-D-
xylopiranosyl-(1↔2)-6-O-tert-butyldiphenylsilyl-1,3,4-tri-
O-benzyl-␤-D-fructofuranoside (11)
DMSO (1 mL) was added dropwise to a solution of oxalyl
chloride (0.4 mL) in CH2Cl2 (25 mL) at –78 °C under an ar-
gon atmosphere. After 5 min, alcohol 6 (1.2 g, 1.1 mmol in
15 mL CH2Cl2) was added and the mixture was stirred at
–78 °C for 30 min. Triethylamine (1 mL) was added, stirring
was prolonged for an additional 15 min at –78 °C, and the
mixture was allowed to reach rt. It was then partitioned be-
tween water (40 mL) and ether (150 mL), the organic phase
was separated, washed with water (2 × 50 mL) and brine
(50 mL), dried, and concentrated. The oily residue was dis-
solved in acetone (20 mL) and titrated with Jones reagent
(3 mL) until TLC (hexane – ethyl acetate, 1:1) indicated the
disappearance of the starting material (ca. 20 min). The ex-
cess of the Jones reagent was decomposed with isopropanol
(5 mL), most of the acetone was removed by vacuum, and
the residue was partitioned between water (50 mL) and ethyl
acetate (100 mL). The organic phase was separated, washed
with brine (50 mL), dried, concentrated, and the crude acid
was methylated with diazometane under standard conditions.
Evaporation of the solvent left an oily residue, which was
purified by column chromatography (hexane – ethyl acetate,
5:1) to give the title methyl uronate (11) (0.80 g,
0.698 mmol, 64%) as a colorless oil. [α]D +19.9°. IR
(film, cm–1) υ: 2930, 2859, 1750 (CO), 1454, 1089, 1028,
737, 698. 1H NMR δ: 5.77 (d, J1,2 = 3.6 Hz, 1H, H-1), 4.78–
4.40 (m, 14H, 12×CH2Ph, H-3′, H-5), 4.30 (dd, J3′4′ = 6.9 Hz,
J4 ′5 ′ = 6.9 Hz, 1H, H-4′), 4.07–4.03 (m, 1H, H-5′), 3.97–
1
1454, 1088, 1073, 1028, 736, 697. H NMR δ: 5.93–5.83
(m, 1H, CH=CH2), 5.52 (d, J1,2 = 3.5 Hz, 1H, H-1), 5.27–
5.22 (m, 1H, -CH2-CH=CH2, J = 17.2 Hz), 5.15 (1H, -CH2-
CH=CH2, J = 10.4 Hz). 13C NMR δ: 134.5 (-CH2-CH=CH2),
117.3 (-CH2-CH=CH2), 103.9 (C-2′), 91.1 (C-1), 83.7, 81.7,
81.3, 79.6, 79.4, 77.4, 71.3 (C-2,3,3′,4,4′,5,5′), 75.5, 74.9,
73.4, 73.3, 72.9, 72.49, 72.47, 71.2 (6×CH2Ph, C-1′ and
-CH2-CH=CH2), 67.9, 61.2 (C-6 and C-6′). MS m/z: 945
[M(C57H62O11) + Na+]. Anal. calcd. for C57H62O11: C 74.17,
H 6.77; found: C 74.0, H 6.8.
6-O-Allyl-6′-O-acroyl-1′,2,3,3′,4,4′-hexa-O-benzylsucrose
(10)
Alcohol 9 (0.355 g, 0.385 mmol) was dissolved in CH2Cl2
(20 mL) containing triethylamine (1 mL) and DMAP (ca.
~20 mg). Acroyl chloride (0.13 mL, 1.5 mmol) was added,
the mixture was stirred for 1 h at rt and then partitioned be-
tween ether (70 mL) and water (50 mL). The organic phase
was separated, dried, concentrated, and the residue was puri-
fied by column chromatography (hexane – ethyl acetate, 3:1)
to give 10 (0.268 g, 0.29 mmol, 75%) as a yellowish oil.
[α]D +41.2°. IR (film): 3070, 3031, 2930, 2857, 1727, 1636,
1
3.91 (m, 2H, both H-6′), 3.87 (dd, J2,3 = 9.3 Hz, J3,4
=
1497, 1454, 1428, 1361, 821, 739, 700. H NMR δ: 6.39
9.3 Hz, 1H, H-3), 3.69 (dd, J4,5 = 9.4 Hz, 1H, H-4), 3.68 (d,
J1 ′A,1 ′B = 11.2 Hz, 1H, H-1′A) 3.48 (d, 1H, H-1′B) 3.47 (dd,
1H, H-2), 3.469 (s, 3H, OCH3), 1.05 (s, 9H, Me3CSi). 13C
NMR δ: 170 (CO), 104.8 (C-2′), 90.1 (C-1), 83.8 (C-3′),
82.7 (C-4′), 81.6 (C-5′), 81.3 (C-3), 79.6 (C-4), 79.4 (C-2),
75.6, 74.9, 73.4, 73.0, 72.6, 72.3 (6×CH2Ph), 70.9 (C-1′),
70.5 (C-5), 64.9 (C-6′), 51.9 (OCH3), 26.9 (Me3CSi), 19.3
(Me3CSi). MS m/z: 1071.8 [M(C71H76O12Si) + Na+].
(dd, J = 1.3, 17.4 Hz, 1H, COCH=CH2), 6.11 (dd, J =
10.5 Hz, 1H, second COCH=CH2), 5.90–5.80 (m, 1H,
CH2CH=CH2), 5.75 (dd, 1H, COCH=CH2), 5.64 (d,
J1,2 = 3.6 Hz, 1H, H-1), 5.22 (dd, J = 17.2, 1.6 Hz, 1H,
CH2CH=CH2), 5.12 (dd, J = 10.4 Hz, 1H, second
CH2CH=CH2). 13C NMR δ: 165.8 (CO), 134.7 (-CO2CH=CH2),
131.0 (-CO2CH=CH2), 128.5–127 (-CH2CH=CH2), 117.1
(-CH2CH=CH2), 104.7 (C-2′), 90.2 (C-1), 83.8, 82.2, 81.9,
79.7, 78.2, 77.7 and 70.7 (C-2,3,3′,4,4′,5,5′), 75.5, 74.8,
73.4, 72.9, 72.6, 72.5, 72.3, 70.9, 68.5, 65.3 (C-1′, C-6,
C-6′, -CH2CH=CH2, and 6×OCH2Ph). MS m/z: 999
[M(C60H64O12) + Na+].
6-O-Allyl-1′,2,3,3′,4,4′-hexa-O-benzylsucrose (9)
To a solution of 6 (1.71 g, 1.52 mmol) and allyl bromide
(6 mL) in CH2Cl2 (40 mL), 50% NaOH (40 mL) and
Bu4NBr (0.15 g, 0.47 mmol) were added. The mixture was
stirred vigorously for 24 h at rt. A second portion of allyl
bromide (4 mL) was added, the stirring was continued over-
night, and the mixture was then partitioned between water
(30 mL) and ether (70 mL). The organic layer was sepa-
rated, washed with water (40 mL), dried, concentrated, and
the product was isolated by column chromatography (hexane –
ethyl acetate, 7:1 to 4:1) to give 6-O-allyl-1′,2,3,3′,4,4′-
Metathesis reaction of 6-O-allyl-6′-O-acroyl-
1′,2,3,3′,4,4′-hexa-O-benzylsucrose (10) catalyzed by
Grubbs II catalyst
Compound 10 (0.250 g, 0.256 mmol) was dissolved in
CH2Cl2 (7 mL) to which Grubbs II catalyst (13.1 mg,
0.015 mmol) was added and the mixture was boiled under
reflux for 3.5 h. The mixture was then partitioned between
© 2006 NRC Canada

496
Can. J. Chem. Vol. 84, 2006
CH2Cl2 (20 mL) and water (30 mL), the organic phase was
separated, and the aqueous one extracted with ether
(10 mL). The combined organic layers were dried, concen-
trated, and the products were partially purified by column
chromatography (hexane – ethyl acetate, 5:1 to 3:1) to afford
unreacted compound 10 (30 mg) and a mixture of four com-
pounds (76 mg) from which the individual products were
isolated by HPLC (hexane – ethyl acetate, 5:2).
3.6 Hz, H-1). 13C NMR δ: 165.9 (CO), 131.1 (-CO2CH=CH2),
129.5 (-CO2CH=CH2), 104.7 (C-2′), 90.3 (C-1), 83.9, 82.3,
81.8, 79.8, 78.3, 77.6, 70.70 (C-2,3,3′,4,4′,5,5′), 75.5,
74.8, 73.4, 72.9, 72.59, 72.50, 71.4, 70.8, 68.6, 65.4
(C-1′,6,6′, -CH2CH=CH2 and 6×CH2Ph). MS m/z: 1947
[M(C118H124O24) + Na+] (strongest signal: 1948 [M + 1 +
Na+]).
E-Isomer 12 was the first to be isolated. IR (film, cm–1) υ:
References
2923, 2856, 1726 (CO), 1454, 1091, 1073, 1028, 736, 697.
1. (a) J.Y.C. Chan, L. Hough, and A.C. Richardson. J. Chem.
Soc. Perkin Trans. 1, 1457 (1985); (b) A. de Raadt and A.E.
Stütz. Tetrahedron Lett. 33, 189 (1992); (c) G. Garndnig, G.
Legler, and A.E. Stütz. Carbohydr. Res. 287, 49 (1996);
(d) F.W. Lichtenthaler. Acc. Chem. Res. 35, 728 (2002).
2. Review: R. Khan. Pure Appl. Chem. 56, 833 (1984), and
refs. therein.
1H NMR (for numbering see Scheme 2) δ: 7.13 (ddd, Jα,β
=
16.1 Hz, Jβ,δ = 7.0 Hz, Jβ, γ = 5.2 Hz, 1H, H-β), 5.81–5.76
(m, 1H, H-α), 5.67 (d, J1,2 = 3.8 Hz, H-1). 13C NMR δ:
165.7 (CO), 147.8 (-CH2CH=CHCO-), 22.3 (-CH=CH-CO-),
102.8 (C-2′), 88.6 (C-1), 84.2, 81.6, 79.9, 78.31, 78.25, 78.18,
71.2 (C-2,3,3′,4,4′,5,5′′), 75.19, 75.13, 74.6, 73.3, 73.1,
72.4, 72.2, 69.9, 67.6, 60.0 (C-1′,6,6′, -CH2CH=CH2 and
6×OCH2Ph). MS m/z: 971 (main signal) [M(C58H60O12) +
Na+] and 987 [M(C58H60O12) + K+] (minor).
3. Review: S. Jarosz and M. Mach. Eur. J. Org. Chem. 769
(2002), and refs. therein.
4. (a) F.W. Lichtenthaler. Carbohydr. Res. 313, 69 (1998); an
overview of sucrose chemistry is included in: F.W.
Lichtenthaler (Editor). Carbohydrates as organic raw materi-
als. VCH Verlagsgesellschaft mbH, Weinheim, Germany.
1991; (b) F.W. Lichtenthaler and S. Mondel. Pure Appl. Chem.
69, 1853 (1997); (c) G. Descotes, J. Gagnaire, A. Bouchu, S.
Thevenet, N. Giry-Panaud, P. Salanski, S. Belniak, A.
Wernicke, S. Porwanski, and Y. Queneau. Pol. J. Chem. 73,
1069 (1999).
5. J. Seibel, R. Moraru, and S. Götze. Tetrahedron, 61, 7081
(2005).
6. S. Jarosz. J. Carbohydr. Chem. 15, 73 (1996).
7. S. Jarosz, M. Mach, and J. Frelek. J. Carbohydr. Chem. 19,
693 (2000).
Z-Isomer 13 was the second to be isolated (contaminated
1
with ca. 30% of 12). H NMR δ: 6.21 (ddd, Jβ,γ = 12.0 Hz,
Jβ,δ = 12.0 Hz, Jα,β = 5.2 Hz, 1H, H-β), 5.77 (ddd, Jα,γ
=
1.8 Hz, Jα,δ = 1.8 Hz, 1H, H-α), 5.54 (d, J1,2 = 3.6 Hz, H-1).
13C NMR δ: 166.1 (CO), 144.8 (-CH=CHCO-), 121.5
(-CH=CH-CO2), 103.7 (C-2′), 90.2 (C-1), 83.7, 81.7, 80.7,
79.7, 79.0, 77.8, 71.6 (C-2,3,3′,4,4′,5,5′), 75.4, 74.6, 73.3,
73.1, 72.4, 72.3 (2×), 70.5, 67.2, 61.9 (C-1′,6′,6, -CH2CH=CH2
and 6×OCH2Ph). MS m/z: 971 (minor signal) [M(C58H60O12) +
Na+] and 987 [M(C58H60O12) + K+] (main).
Macrocyclic dimer 14 was the third to be isolated (con-
1
taminated with 12, 13, and 15; ca. 5%–10% each). H NMR
8. S. Jarosz and A. Listkowski. J. Carbohydr. Chem. 22, 753
(2003).
9. S. Jarosz, A. Listkowski, B. Lewandowski, Z. Ciunik, and A.
δ: 6.83 (ddd, Jα,β = 15.8 Hz, Jβ,γ = 4.0 Hz, Jβ,δ = 4.0 Hz, 1H,
H-β), 5.96 (ddd, Jα,γ = 2.0 Hz, Jα,δ = 2.0 Hz, 1H, H-α), 5.66
(d, J1,2 = 3.7 Hz, H-1). 13C NMR δ: 165.8 (CO), 145.6
(-CH2CH=CHCO-), 120.0 (-CH2CH=CHCO-), 104.6 (C-2′),
89.4 (C-1), 89.4, 83.6, 82.1, 81.3, 80.0, 77.7, 70.9 (C-
2,3,3′,4,4′,5,5′), 75.5, 74.9, 73.5, 72.9, 72.5, 72.3, 71.6,
70.1, 69.3, 64.1 (C-1′,6,6′, -CH2CH=CH2 and 6×CH2Ph).
MS m/z: 1919 [M(C116H120O24) + Na+] (strongest signal:
1920 [M + 1 + Na+]).
Brzuszkiewicz. Tetrahedron, 61, 8485 (2005)
10. (a) F. Franke and R.D. Guthrie. Aust. J. Chem. 30, 639 (1977);
(b) F. Franke and R.D. Guthrie. Aust. J. Chem. 31, 1285
(1978); (c) H. Karl, C.K. Lee, and R. Khan. Carbohydr. Res.
101, 31 (1982).
11. (a) A.K. Chatterjee and R.H. Grubbs. Org. Lett. 1, 1751
(1999); (b) T.M. Trnka and R.H. Grubbs. Acc. Chem. Res. 34,
18 (2001); (c) S.B. Garber, J.S. Kingsbury, B.L. Gray, and
A.H. Hoveyda. J. Am. Chem. Soc. 122, 8168 (2000).
12. S.J. Connon and S. Blechert. Angew. Chem. Int. Ed. 42, 1900
(2003).
1
Open-chain dimer 15 was the fourth to be isolated. H
NMR δ: 6.36 (dd, Jα,β = 17.4 Hz, Jβ,γ = 1.4 Hz, 1H, H-β),
6.09 (dd, Jα,γ = 10.4 Hz, 1H, H-α), 5.72 (dd, 1H, H-γ), 5.70
(dd, Jδ,φ = 3.0 Hz, Jδ,ε = 3.0 Hz, 1H, H-δ), 5.62 (d, J1,2
=
© 2006 NRC Canada