Alternative approaches towards glycosylated eight-membered ring compounds employing Claisen rearrangement of mono and disaccharide allyl vinyl ether precursors

Article abstract of DOI:10.1016/j.tetasy.2005.02.027

Highly functionalized eight-membered rings having a glycosidic residue were synthesized in two different ways involving either glycosylation of a sugar-derived cyclooctenone with high stereocontrol as well as a Claisen rearrangement of a disaccharide deri

Full text of DOI:10.1016/j.tetasy.2005.02.027

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 1631–1638
Alternative approaches towards glycosylated eight-membered
ring compounds employing Claisen rearrangement of mono
and disaccharide allyl vinyl ether precursors
Stefan Jurs and Joachim Thiem*
¨
Institut fu¨r Organische Chemie der Universita¨t, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany
Received 25 January 2005; accepted 24 February 2005
Available online 31 March 2005
Dedicated to the memory of Professor Christian Pedersen, Technical, University of Denmark, Lyngby-Copenhagen,
the excellent Danish, carbohydrate chemist
Abstract—Highly functionalized eight-membered rings having a glycosidic residue were synthesized in two different ways involving
either glycosylation of a sugar-derived cyclooctenone with high stereocontrol as well as a Claisen rearrangement of a disaccharide
derivative.
ꢀ 2005 Elsevier Ltd. All rights reserved.
1. Introduction
conditions and selective tosylation gave 5. The introduc-
tion of benzyl groups simultaneously caused the substi-
tution of the tosylate by a bromide, hence, this
Finkelstein exchange was driven to completion by both
heating and an extra addition of NaBr. The preparation
of the enolether 7 from 6, accomplished by silver fluo-
ride,7 assisted the elimination of hydrogen bromide.
Simple heating to 185 ꢁC for 1 h in nitrobenzene fur-
nished the desired 5-cyclooctenone 8 in over 80% yield.
Glycosides of eight-membered carbocycles are excep-
tionalstructuralmotifs in nature and can be found in
a number of noveltaxane derivatives as well as in fur-
ther terpenoids based on the fusicoccane framework.2
The biological functions of these structures are not fully
understood at present, however, some of these com-
pounds seem to have an impact on plant growth and
development and stimulate seed germination.3
1
Upon reduction using either LiAlH4 or triisobutylalu-
minium, only one diastereomer of the 5-cyclooctenol 9
was formed. It is interesting to note that only minor
changes of the coupling constant values could be
observed after reduction of 8 to 9. An additionalalrge
coupling constant (J1,2 = 8.5 Hz) indicates a trans-
arrangement and therefore (S)-configuration of the
new stereogenic centre with an equatorialhydroxy
group. Strong NOE interactions between H-2, H-4 and
H-7 in compound 8 suggest a boat-chair like geometry,
the most common conformation amongst eight-mem-
bered rings.8 The same conformation is likely to apply
to 9 in view of the lack of spectral changes. The second-
ary hydroxyl function could be glycosylated9 using the
benzylated b-trichloroacetimidate 1010 to give selectively
the 1,2-cis configured a-glucoside 11. The decrease of
J2,3 = 4.7 Hz in 9 to J4,5 = 1.9 Hz in 11 is remarkable
since all other coupling constants in both compounds
again remain similar. Hence, 11 is assumed to feature
2. Results and discussion
An attractive approach to chiraloxygenated eight-mem-
bered rings consists of the ring enlargement of a pyra-
nose-derived allyl vinyl ether to the corresponding
5-cyclooctenone derivative.4,5 Thus, D-glucose 1 was
transformed into the peracetylated a-bromide 2 (Scheme
1) and subsequently alkylated to afford the C-vinyl
glucoside 36 as an inseparable mixture of anomers
(a:b = 0.2:1.0). The initially formed C-glucoside with
unprotected hydroxylgroups had to be peracetyalted
in order to facilitate the removal of large amounts of
´
magnesium salts. Deacetylation of 3 under Zemplen
*
Corresponding author. Tel.: +49 40 42838 4241; fax: +49 40 42838
4325; e-mail: joachim.thiem@chemie.uni-hamburg.de
0957-4166/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2005.02.027

1632
S. Ju¨rs, J. Thiem / Tetrahedron: Asymmetry 16 (2005) 1631–1638
R''
RO
O
O
RO
RO
RO
RO
iii
D-glucose
OR
OR
R'
R'
1
i
2: R = Ac, R' = α-Br
5: R = H, R' = CH=CH2, R'' = OTs
6: R = Bn, R' = β-CH=CH2, R'' = Br
iv
3: R = Ac, R' = CH=CH2
ii
4: R = H, R' = CH=CH2
H
2
BnO
BnO
H
O
BnO
O
H
4
7
v
BnO
BnO
vi
OBn
7
8
BnO
BnO
O
BnO
BnO
BnO
HO
BnO
BnO
BnO
O
BnO
1'
vii
OBn
viii
O
BnO
BnO
+
NH
O
OBn
BnO
6
Cl3C
9
10
11
1
Scheme 1. Reagents and conditions: (i) CH2@CHMgBr, THF, reflux, then Ac2O, Py, 41%; (ii) NaOMe, MeOH, Amberlite IR 120 H+, 100%; (iii)
TsCl, Py, 93%; (iv) BnBr, NaH, DMF, then NaBr, 80 ꢁC, 31%; (v) AgF, Py, 80%; (vi) PhNO2, 185 ꢁC, 81%; (vii) LiAlH4, THF, 88%; (viii) 10,
TMSOTf, DCM, molecular sieves 4 A, 51%.
˚
a new interesting spatialarrangement of oxygenated func-
tionalities, presumably boat-chair like in the cycloocten-
ylresidue, that coudl be of interest with respect to
disaccharide mimetics. Moreover, the newly generated
double bond offers opportunities for the introduction
of further functionalities.
this solvent mixture can be attributed to the high heat
capacity of decane, granting an improved energy trans-
fer onto the substrate, and the absence of oxygen in both
solvents, leading to significantly less decomposition. The
use of triisobutylaluminium as a catalyst for the Claisen
rearrangement, which was reported to be successfulin
12,13
severalsynthetic undertakings,
did not prove effec-
The selective introduction of a glycosidic residue to one
of the benzylprotected hydroxylgroups in 8 was figured
to be more complicated. To circumvent random glyco-
sylation of deprotected 8, the introduction of the glyco-
side should be carried out at an earlier stage in the
synthesis of the 5-cyclooctenone with the aid of conven-
tionalprotecting group manipualtions. For this pur-
pose, D-mannose 12 was converted into the acetylated
a-bromide 13, which in turn was used for the intro-
duction of a C-vinylgroup ( Scheme 2). Subsequent
deacetylation followed by selective silylation and
isopropylidenation led to the mannose derivative 17
unprotected at the 4-position. The glycosylation of the
latter using 10 (a:b = 1.0:0.8) under the same conditions
as for the synthesis of 11 gave, selectively, the protected
Glca1-4Man disaccharide derivative 18 (53%). The fol-
lowing steps included desilylation (TBAF, THF, 61%),
tosylation (TsCl, py, 92%) and substitution of the tosyl-
ate by a bromide (NaBr, DMF, 70 ꢁC, quant.) to facili-
tate elimination using silver fluoride to give precursor 22
in quantitative yields after reaction (TLC), although in
moderate yields after work-up.11 In the subsequent
experiment it was shown that the properly functional-
ized disaccharide with an allyl vinyl ether substructure
22 could be thermally converted into the corresponding
glycosylated cyclooctenone 23 (70%) by a Claisen rear-
rangement. Precursor 22 was dissolved in a decane/tolu-
ene mixture (ratio 5:1) and heated to 180 ꢁC for 15 min
in a microwave device. The pronounced effectiveness of
tive in this case, presumably due to the high density of
oxygenated functionalities. The boat-chair conform-
ation of 23 was also established by thorough analysis
of NOE spectra and coupling constants. In this case, a
relatively large coupling constant J1,2 = 8.9 Hz was ob-
served when compared to compound 8 (J1,2 = 4.4 Hz).
This can be attributed to the fused 1,3-dioxolane ring
causing a somewhat more strained conformation.
3. Conclusion
The novel enantiopure cyclooctenyl glycosides reported
herein are of crucialinterest with regards to disaccharide
mimetics due to their unique conformationalproperties
consisting of a boat-chair conformation in which the
chair part is highly oxygenated and therefore bears
exceptionalresembalnce to naturalsubstrates. Further
studies including complete deprotection as well as more
functionalizations of the related compounds will be pre-
sented in due course.
4. Experimental
4.1. General
Solvents were purified and dried according to standard
procedures. The microwave experiment was performed

S. Ju¨rs, J. Thiem / Tetrahedron: Asymmetry 16 (2005) 1631–1638
1633
R'O
RO
RO
RO
OR
OR
O
O
ii
iv
D-mannose
RO
RO
iii
R'
12
15: R = R' =H
13: R = Ac, R' = α-Br
i
16: R = H, R' = TBDPS
14: R = Ac, R' = CH=CH2
BnO
BnO
O
TBDPSO
O
O
ix
v
HO
O
R
O
O
BnO
10
OBn
O
O
17
vi
18: R = OTBDPS
19: R = OH
vii
viii
20: R = OTs
21: R = Br
BnO
BnO
O
BnO
BnO
O
BnO
BnO
x
1'
OBn
OBn
2
O
O
O
O
O
O
O
23
22
O
1
5
Scheme 2. Reagents and conditions: (i) CH2@CHMgBr, THF, reflux, then Ac2O, Py, 45%; (ii) NaOMe, MeOH, Amberlite IR 120 H+, 100%; (iii)
˚
TBDPSCl, imidazole, DMF, 80%; (iv) CH3C(OCH3)2CH3, acetone, p-TSA, 62%; (v) 10, TMSOTf, DCM, molecular sieves 4 A, 53%; (vi) TBAF,
THF, 61%; (vii) TsCl, Py, cat. DMAP, 83%; (viii) NaBr, DMF, 70 ꢁC, 100%; (ix) AgF, Py, 21%; (x) n-decane/toluene 5:1, 180 ꢁC, 70%.
in a CEM microwave system (Discover, 300 W maxi-
mum power output). Petroleum ether used refers to
bp 50–70 ꢁC. TLC was performed on silica gel 60-
coated aluminium sheets (Merck or Macherey-Nagel),
with detection by UV at 254 nm and by heating with
H2SO4 (5% in EtOH). Flash chromatography was car-
ried out on silica gel 60 (0.04–0.063 mm; Merck,
Macherey-Nagelor ICN). NMR spectra were recorded
on a Bruker AMX-400 NMR spectrometer (1H:
400 MHz; 13C: 100 MHz) and analyzed with the
respective solvent peaks as references. IR spectra were
recorded on a Thermo Electron FT-IR spectrometer
(Nicolet Avatar 370). Melting points were determined
on a Leitz apparatus and are uncorrected. The optical
rotations were measured on a Perkin–Elmer 243 or 341
polarimeter at 20 ꢁC. With regards to nomenclature, in
most cases the sugar nomenclature14 was applied
except for the more complex oligohydroxy cyclooctene
derivatives.
for 5 h. The reaction mixture was poured onto ice/
water and neutralized with acetic acid. The aqueous
phase was evaporated and the residue dried for several
hours in vacuo. After suspension of the residue in
pyridine (200 mL) and addition of acetic anhydride
(200 mL) at 0 ꢁC, the reaction mixture was stirred for
2 days at room temperature. The mixture was then
poured into iced water and extracted severaltimes with
dichloromethane. After evaporation of the solvent, the
residue was purified by column chromatography
(petroleum ether/ethyl acetate 3:1) to give 2.970 g of
3 (8.29 mmol, 41%, colourless crystals) as an insepar-
able anomeric mixture (a:b ꢀ 0.2:1.0). C16H22O9
(358.3); MALDI-TOF: [M+Na]+: 381, [M+K]+: 397;
b-anomer: 1H NMR (400 MHz, CDCl3): d = 1.99,
2.00, 2.02, 2.08 (4 · s, 4 · 3H, Ac), 3.69 (ddd, 1H,
H-7, J6,7 = 9.7, J7,8a = 4.8, J7,8b = 2.2 Hz), 3.86 (dd,
1H, H-3, J2,3 = 7.1, J3,4 = 9.7 Hz), 4.12 (dd, 1H,
H-8b, J7,8b = 2.2, J8a,8b = 12.4 Hz), 4.24 (dd, 1H, H-
8a, J7,8a = 4.8, J8a,8b = 12.4 Hz), 4.93 (dd ꢁ t, 1H,
4.2. 4,5,6,8-Tetra-O-acetyl-3,7-anhydro-1,2-dideoxy-D-
glycero-D-gulo-oct-1-enitol [b-anomer] and 4,5,6,8-tetra-
O-acetyl-3,7-anhydro-1,2-dideoxy-D-glycero-D-ido-oct-1-
enitol [a-anomer] 3
H-4, J3,4 = J4,5 = 9.7 Hz), 5.08 (dd ꢁ t, 1H, H-6, J5,6
J6,7 = 9.7 Hz), 5.22 (dd ꢁ t, 1H, H-5, J4,5 = J5,6
=
=
9.7 Hz), 5.26–5.37 (m, 2H, H-1a, H-1b, J1a,2 = 17.4,
J1b,2 = 10.4 Hz), 5.75 (ddd, 1H, H-2, J2,3 = 7.1 Hz)
ppm; 13C NMR (100 MHz, CDCl3): d = 20.75, 20.79,
20.84, 20.90 (4C, 4 · acetyl–Me), 62.41 (1C, C-8),
68.66, 71.37, 74.09, 75.74, 79.59 (5C, C-3, C-4, C-5,
C-6, C-7), 120.21 (1C, C-1), 133.35 (1C, C-2), 169.62,
169.63, 170.50, 170.87 (4C, 4 · acetyl–CO2) ppm; Anal.
Calcd for C16H22O9 (358.3): C, 53.62; H, 6.20. Found
C, 53.58; H, 6.24.
Under an argon atmosphere, a solution of 2,3,4,6-tetra-
O-acetyl-a-D-glucopyranosylbromide 215 (8.23 g, 20.00
mmol) in dry THF (60 mL) was added dropwise to a
solution of vinyl magnesium bromide in THF
(200 mL, 1 M, 200 mmol). At the end of the exother-
mic reaction, heating under reflux was continued

1634
S. Ju¨rs, J. Thiem / Tetrahedron: Asymmetry 16 (2005) 1631–1638
4.3. 3,7-Anhydro-1,2-dideoxy-D-glycero-D-gulo-oct-1-eni-
tol [b-anomer] and 3,7-anhydro-1,2-dideoxy-D-glycero-D-
ido-oct-1-enitol [a-anomer] 4
solution was extracted with dichloromethane and the
combined organic extracts washed with saturated
sodium chloride solution. After evaporation of the
solvents, the residue was purified by column
chromatography (petroleum ether/ethyl acetate 20:1)
to give 0.921 g of 6 (1.759 mmol, 36%, yellowish solid)
To a solution of 3 (2.790 g, 8.288 mmol) in dry metha-
nol(50 mL) was added sodium methoxide (NaOMe)
untilpH 9 was reached. The reaction mixture was stir-
red for severalhours untilTLC control(dichol rometh-
ane/methanol10:1) confirmed compelte reaction. After
neutralization with Amberlite IR 120 H+, the solution
was filtered and the solvent evaporated to give
1.570 g of 4 (8.254 mmol, 100%) as an inseparable ano-
meric mixture (a:b ꢀ 0.2:1.0); C8H14O5 (190.2); MAL-
as pure b-anomer; mp (solid after chromatography):
20
65–67 ꢁC; ½aŠ ¼ þ19:4 (c 0.5, CHCl3); C29H31O4Br,
D
523.5; MALDI-TOF: [M+Na]+: 545, 547; [M+K]+:
561; 1H NMR (400 MHz, CDCl3): d = 3.35 (dd ꢁ t,
1H, H-4, J3,4 = J4,5 = 9.4 Hz), 3.47–3.51 (m, 1H, H-7,
J6,7 = 9.4, J7,8a = 2.5, J7,8b = 4.3 Hz), 3.60–3.64 (m, 2H,
H-6, H-8b, J5,6 = J6,7 = 9.4, J7,8b = 4.3, J8a,8b = 10.9
Hz), 3.70 (dd, 1H, H-8a, J7,8a = 2.5, J8a,8b = 10.9 Hz),
3.75 (dd ꢁ t, 1H, H-5, J4,5 = J5,6 = 9.4 Hz), 3.84 (dd,
1H, H-3, J2,3 = 6.1, J3,4 = 9.4 Hz), 4.67, 4.74, 4.76,
4.88, 4.94, 4.95 (6 · d, 6 · 1H, OCH2), 5.30–5.33 (m,
1H, H-1b, J1b,2 = 10.7, J1a,1b = 1.3 Hz), 5.49 (ddd ꢁ dt,
1H, H-1a, J1a,2 = 17.3, J1a,1b = 1.3 Hz), 5.93–6.01 (m,
1H, H-2, J1a,2 = 17.3, J1b,2 = 10.7, J2,3 = 6.1 Hz), 7.28–
1
DI-TOF: [M+Na]+: 213, [M+K]+: 229; b-anomer: H
NMR (400 MHz, MeOD): d = 3.09 (dd ꢁ t, 1H, H-4),
3.25–3.38 (m, 6H, H-5, H-6, H-7, 3 · OH), 3.60–3.68
(m, 2H, H-3, H-8b, J2,3 = 5.9 Hz), 3.86 (dd, 1H, H-
8a), 5.21 (ddd, 1H, H-1b), 5.39 (ddd, 1H, H-1a), 5.93
(ddd, 1H, H-2) ppm; 13C NMR (100 MHz, CD3OD):
d = 63.10 (1C, C-8), 71.86, 75.40, 79.65, 81.57, 81.67
(5C, C-3, C-4, C-5, C-6, C-7), 117.68 (1C, C-1),
136.93 (1C, C-2) ppm; Anal. Calcd for C8H14O5
(190.2): C, 50.51; H, 7.42; Found: C, 48.88; H, 7.71
(hygroscopic).
7.38 (m, 15H, Ar) ppm. 13C NMR (100 MHz, CDCl3):
d = 33.57 (1C, C-8), 75.31, 75.48, 75.78 (3C, OCH2),
77.21, 79.79, 79.99, 82.78, 86.57 (5C, C-3, C-4, C-5,
C-6, C-7), 118.57 (1C, C-1), 127.85–128.75 (15C, Ar),
135.00 (1C, C-2), 138.05, 138.11, 138.58 (3C, Ar) ppm;
Anal. Calcd for C29H31O4Br, 523.5: C, 66.53; H, 5.98.
Found: C, 65.71; H, 5.99.
4.4. 3,7-Anhydro-1,2-dideoxy-8-O-(4-toluenesulfonyl)-D-
glycero-D-gulo-oct-1-enitol [b-anomer] and 3,7-anhydro-
1,2-dideoxy-8-O-(4-toluenesulfonyl)-D-glycero-D-ido-oct-
1-enitol [a-anomer] 5
4.6. 3,7-Anhydro-4,5,6-tri-O-benzyl-1,2,8-trideoxy-D-
gulo-oct-1,7-dienitol 7
To a solution of 4 (1.432 g, 7.530 mmol) in dry pyridine
(50 mL) was added p-toluenesulfonyl chloride (1.58 g,
8.29 mmol) at 0 ꢁC. The solution was stirred at room
temperature for 2 days. If necessary, further small por-
tions of p-toluenesulfonyl chloride were added to effect
the complete consumption of starting material. The
reaction was terminated by the addition of water fol-
lowed by evaporation of the solvents and co-distilla-
tion with toluene. Column chromatography of the
residue (dichloromethane/methanol 10:1) gave 2.42 g 5
(7.03 mmol, 93%) as an inseparable mixture of anomers
(a:b ꢀ 0.2:1.0); C15H20O7S (344.4); MALDI-TOF:
[M+Na]+: 367, [M+K]+: 383; b-anomer: 1H NMR
(400 MHz, CDCl3): d = 2.43 (s, 3H, Ts–Me), 3.20–3.79
(m, 7H, H-4, H-5, H-6, H-7, 3 · OH), 4.23–4.31 (m,
2H, H-8a/b), 5.23 (d, 1H, H-1b), 5.30 (d, 1H, H-1a),
5.85 (m, 1H, H-2), 7.32, 7.78 (2 · d, 4H, Ar) ppm; 13C
NMR (100 MHz, CDCl3): d = 21.79 (1C, Ts–Me),
69.52 (1C, C-8), 69.86, 73.62, 76.94, 78.11, 80.28 (5C,
C-3, C-4, C-5, C-6, C-7), 118.57 (1C, C-1), 128.16,
130.03, 132.81 (5C, Ar), 134.75 (1C, C-2) ppm.
To a solution of 6 (1.147 g, 2.190 mmol) in dry pyridine
(40 mL) was added silver fluoride (1.100 g, 8.67 mmol).
The solution was stirred for 2 days at room temperature
under light exclusion until TLC control confirmed the
complete consumption of starting material. After dilu-
tion with dichloromethane followed by filtration, evapo-
ration and co-distillation with toluene the residue was
purified by column chromatography (petroleum ether/
ethylacetate 20:1) to give 0.780 g 7 (1.760 mmol, 80%)
as colourless crystals (pure b-anomer). Mp (solid
20
after chromatography): 55 ꢁC; ½aŠ ¼ À75:1 (c 0.2,
D
CHCl3); C29H30O4, 442.6; MALDI-TOF: [M+Na]+:
465, [M+K]+: 481; 1H NMR (400 MHz, CDCl3):
d = 3.28 (dd, 1H, H-4, J3,4 = 9.8, J4,5 = 7.5 Hz), 3.57
(dd ꢁ t, 1H, H-5, J4,5 = J5,6 = 7.5 Hz), 3.81 (d, 1H,
H-6, J5,6 = 7.5 Hz), 3.94–3.98 (m, 1H, H-3, J2,3 = 6.4,
J3,4 = 9.8 Hz), 4.45–4.70 (m, 8H, H-8a/b, OCH2), 5.16–
5.19 (m, 1H, H-1b, J1a,1b = 1.3, J1b,2 = 10.7 Hz), 5.31–
5.36 (m, 1H, H-1a, J1a,1b = 1.3, J1a,2 = 17.3 Hz), 5.76–
5.34 (m, 1H, H-2, J1a,2 = 17.3, J1b,2 = 10.7, J2,3 = 6.4
Hz), 7.10–7.24 (m, 15H, Ar) ppm. 13C NMR
(100 MHz, CDCl3): d = 72.83, 74.54, 74.68 (3C,
OCH2), 78.99, 79.49, 82.12, 84.50 (4C, C-3, C-4, C-5,
C-6), 94.94 (1C, C-8), 118.65 (1C, C-1), 127.84–128.60
(15C, Ar), 135.08 (1C, C-2), 138.02, 138.13, 138.46
(3C, Ar), 156.10 (1C, C-7) ppm.
4.5. 3,7-Anhydro-4,5,6-tri-O-benzyl-8-bromo-1,2,8-tride-
oxy-D-glycero-D-gulo-oct-1-enitol 6
To a solution of 5 (1.692 g, 4.913 mmol) in dry DMF
(45 mL) were added benzylbromide (4.67 mL,
39.3 mmol) and sodium hydride (1.179 g of a 60% sus-
pension in paraffine, 29.48 mmol) one after another
whilst stirring. After 3 h, sodium bromide was added
(2.53 g, 24.56 mmol), the solution heated to 80 ꢁC and
stirring continued overnight. The reaction was termi-
nated by the addition of ethylacetate and water. The
4.7. cis-(2S,3R,4S)-2,3,4-Tribenzyloxycyclooct-5-enone 8
A solution of 7 (0.758 g, 1.710 mmol) in nitrobenzene
(20 mL) was placed in a preheated oil bath and heated
at 185 ꢁC for 1 h. After evaporation of the solvent, the

S. Ju¨rs, J. Thiem / Tetrahedron: Asymmetry 16 (2005) 1631–1638
1635
20
D
residue was purified by column chromatography (petro-
leum ether/ethyl acetate 10:1) to give 0.612 g
(1.383 mmol, 81%) as an orange syrup. C29H30O4,
(20 lmol, 51%); ½aŠ ¼ þ17:3 (c 1, CHCl3); C63H66O9,
8
967.3; MALDI-TOF: [M+Na]+ = 989, [M+K]+ = 1005;
1H NMR (500 MHz, C6D6): d = 1.66–1.80 (m, 3H, H-
8b, H-7a/b), 2.79–2.86 (m, 1H, H-8a), 3.57 (dd, 1H,
442.6; MALDI-TOF: [M+Na]+: 465, [M+K]+: 481;
20
½aŠ ¼ þ20:4 (c 1, CHCl3); m (film/cmÀ1): 1719 (C@O);
H-20, J1 ,2 = 3.2, J2 ,3 = 9.5 Hz), 3.70, 3.73 (2 · dd,
0
0
0
0
D
1H NMR (500 MHz, C6D6): d = 1.77–1.83, 1.98–2.07,
2.59–2.65 (3 · m, 4H, H-7a/b, H-8a/b), 3.72 (dd, 1H,
H-3, J2,3 = 4.4, J3,4 = 8.8 Hz), 4.07 (d, 1H, H-2,
J2,3 = 4.4 Hz), 4.15, 4.20 (2 · d, 2 · 1H, OCH2), 4.24
(dd, 1H, H-4, J3,4 = 8.8, J4,5 = 6.6 Hz), 4.38, 4.51
(2 · d, 2 · 1H, OCH2), 4.73 (s, 2H, OCH2), 5.54–5.63
(m, 2H, H-5, H-6, J4,5 = 6.6, J5,6 = 11.4 Hz) ppm. 13C
NMR (100 MHz, CDCl3): d = 23.68 (1C, C-7), 42.35
(1C, C-8), 71.87, 72.51, 74.65 (3C, OCH2), 77.87,
80.31, 84.87 (3C, C-2, C-3, C-4), 127.62, 127.79,
127.91, 128.04, 128.44, 128.47, 128.60, 131.67, 131.71
(15C, Ar), (2C, C-5, C-6), 137.66, 138.47, 138.50 (3C,
Ar), 212.58 (1C, C-1) ppm.
2 · 1H, H-60a/b, J5 ,6 a = 4.1, J5 ,6 b = 2.0, J6 a,6 b
0
0
0
0
0
0
=
10.5 Hz), 3.76 (dd ꢁ t, 1H, H-40, J3 ,4 = J4 ,5 = 9.5 Hz),
3.88 (dd, 1H, H-4, J3,4 = 8.5, J4,5 = 1.9 Hz), 4.00 (dd,
1H, H-5, J4,5 = 1.9, J5,6 = 8.2 Hz), 4.05, 4.29 (2 · d,
2 · 1H, OCH2), 4.40–4.43 (m, 1H, H-6, J5,6 = 8.2 Hz),
4.67, 4.76, 4.88, 4.90 (4 · d, 4 · 1H, OCH2), 4.92 (d,
0
0
0
0
1H, H-10, J1 ,2 = 3.2), 4.98, 5.04 (2d, 2 · 1H, OCH2),
5.26 (dd ꢁ t, 1H, H-3, J2,3 = J3,4 = 8.5 Hz), 5.68–
5.74 (m, 1H, H-2, J1,2 = 10.4, J2,3 = 8.5 Hz), 5.77–5.82
(m, 1H, H-1, J1,2 = 10.4 Hz), 7.02–7.44 (m, 35H,
Ar) ppm. 13C NMR (100 MHz, C6D6): d = 20.89 (1C,
C-8), 26.48 (1C, C-7), 69.45 (1C, C-60), 71.24 (1C,
C-50), 71.69, 71.86, 72.96, 73.14 (4C, OCH2), 73.26
(1C, C-6), 74.66, 74.71, 75.21 (3C, OCH2), 78.59 (1C,
C-40), 78.87 (1C, C-3), 80.86, 80.94 (2C, C-5, C-20),
82.00 (1C, C-30), 85.31 (1C, C-4), 93.78 (1C, C-10),
126.87–128.75 (42C, Ar), 130.60 (1C, C-2), 131.80
(1C, C-1) ppm.
0
0
4.8. cis-(1S,2R,3R,4S)-2,3,4-Tribenzyloxycyclooct-5-
en-1-ol 9
To a solution of 8 (92 mg, 208 lmol) in THF (4 mL)
was added LiAlH4 (14 mg, 369 lmol) at 0 ꢁC and stir-
ring continued overnight. Water was added to destroy
excess LiAlH4. The precipitate was diluted with a small
amount of 2 M sulphuric acid. The solution was di-
luted with chloroform and the organic phase washed
with water. After another extraction of the aqueous
phase with chloroform the combined organic phases
were evaporated. Column chromatography of the resi-
due (petroleum ether/ethyl acetate 10:1) gave 81 mg of
9 (182 lmol, 88%) as a yellowish syrup; C29H32O4,
4.10. 4,5,6,8-Tetra-O-acetyl-3,7-anhydro-1,2-dideoxy-D-
glycero-D-galacto-oct-1-enitol [b-anomer] and 4,5,6,8-
tetra-O-acetyl-3,7-anhydro-1,2-dideoxy-D-glycero-D-talo-
oct-1-enitol [a-anomer] 14
Under an argon atmosphere, a solution of 1316 (8.19 g,
19.92 mmol) in dry THF (70 mL) was added dropwise
to a solution of vinyl magnesium bromide in THF
(200 mL, 1 M, 200 mmol). After the end of the exother-
mic reaction heating under reflux was continued for 5 h.
The reaction mixture was poured into iced water and
neutralized with acetic acid. The aqueous phase was
evaporated and the residue dried for severalhours in
vacuo. After suspension of the residue in pyridine
(150 mL) and addition of acetic anhydride (150 mL) at
0 ꢁC, the reaction mixture was stirred for 2 days. The
mixture was then poured into ice water and extracted
with dichloromethane. After evaporation of the solvent
the residue was purified by column chromatography
(petroleum ether/ethyl acetate 3:1) to give 3.177 g of 14
(8.86 mmol, 45%, white solid) as an inseparable ano-
meric mixture (a:b ꢀ 0.4:1.0). C16H22O9, 358.4; MAL-
444.6; MALDI-TOF: [M+Na]+: 467, [M+K]+: 483;
20
D
½aŠ ¼ À4:8 (c 1, CHCl3); 1H NMR (500 MHz,
C6D6): d = 1.79–1.89, 1.96–2.03, 2.52–2.61 (3 · m, 4H,
H-7a/b, H-8a/b), 3.29 (s, 1H, OH), 3.66 (dd, 1H,
H-3, J2,3 = 4.7, J3,4 = 7.9 Hz), 3.77 (dd, 1H, H-2,
J1,2 = 8.5, J2,3 = 4.7 Hz), 4.18–4.21 (m, 2H, H-1,
OCH2), 4.39, 4.46 (2 · d, 2 · 1H, OCH2), 4.61 (d,
2H, OCH2), 4.78 (d, 1H, OCH2), 4.82 (dd ꢁ t, 1H,
H-4, J3,4 = J4,5 = 7.9 Hz), 5.56–5.60 (m, 1H, H-5,
J4,5 = 7.9, J5,6 = 10.9 Hz), 5.71–5.77 (m, 1H, H-6,
J5,6 = 10.9 Hz), 7.07–7.35 (m, 15H, Ar) ppm. 13C
NMR (100 MHz, C6D6): d = 22.21 (1C, C-7), 32.42
(1C, C-8), 70.71, 78.97, 81.60, 85.20 (4C, C-1, C-2,
C-3, C-4), 71.40, 73.61, 74.95 (3C, OCH2), 127.70–
128.62, 138.93, 139.09, 139.47 (18C, Ar), 129.76,
133.68 (2C, C-5, C-6) ppm.
DI-TOF: [M+Na]+: 381, [M+K]+: 397; b-anomer: H
1
NMR (400 MHz, CDCl3): d = 1.98, 2.04, 2.09, 2.13
(4 · s, 4 · 3H, Ac), 3.68 (ddd, 1H, H-7, J6,7 = 9.9,
J7,8a = 5.6, J7,8b = 2.5 Hz), 4.08–4.18 (m, 2H, H-3,
H-8b, J2,3 = 5.3, J3,4 = 1.3, J7,8b = 2.5, J8a,8b = 12.2 Hz),
4.27 (dd, 1H, H-8a, J7,8a = 5.6, J8a,8b = 12.2 Hz), 5.08
(dd, 1H, H-5, J4,5 = 3.4, J5,6 = 9.9 Hz), 5.24 (ddd ꢁ dt,
1H, H-1b, J1a,1b = 1.3, J1b,2 = 10.8), 5.25 (dd ꢁ t, 1H,
H-6, J5,6 = J6,7 = 9.9 Hz), 5.85 (ddd ꢁ dt, 1H, H-1a,
J1a,1b = 1.3, J1a,2 = 17.5 Hz), 5.40 (dd, 1H, H-4,
J3,4 = 1.3, J4,5 = 3.4 Hz), 5.72 (ddd, 1H, H-2,
J1a,2 = 17.5, J1b,2 = 10.8, J2,3 = 5.3 Hz) ppm. 13C NMR
(100 MHz, CDCl3): d = 20.77, 20.83, 20.86, 20.95 (4C,
Ac), 63.04 (1C, C-8), 66.23 (1C, C-6), 70.05 (1C, C-4),
72.41 (1C, C-5), 76.28 (1C, C-7), 77.57 (1C, C-3),
118.59 (1C, C-1), 132.43 (1C, C-2), 169.84, 170.35,
170.57, 170.91 (4C, acetyl–CO2) ppm; Anal. Calcd for
4.9. [cis-(3S,4R,5S,6S)-3,4,5-Tribenzyloxycycloocten-6-
yl]-20,30,40,60-tetra-O-benzyl-a-D-glucopyranoside 11
To a solution of 9 (17 mg, 38 lmol) in dry dichlorometh-
ane (1.3 mL) with molecular sieves was added a solution
of TMSOTf in dichloromethane (40 lL, concentration
approx. 0.223 M, 9 lmol) at 0 ꢁC under an argon atmo-
sphere. Afterwards, a solution of 10 (41 mg, 60 lmol) in
dichloromethane (1.1 mL) was added at 0 ꢁC. The reac-
tion mixture was stirred overnight and terminated by the
addition of three drops of triethylamine. Evaporation of
the solvent and chromatography of the residue (petro-
leum ether/ethyl acetate 12:1) gave 19 mg of 11

1636
S. Ju¨rs, J. Thiem / Tetrahedron: Asymmetry 16 (2005) 1631–1638
C16H22O9, 358.4: C, 53.62; H, 6.20. Found: C, 52.95; H,
6.20.
4.13. 3,7-Anhydro-8-O-tert-butyldiphenylsilyl-1,2-dide-
oxy-4,5-di-O-isopropylidene-D-glycero-D-galacto-oct-1-
enitol 17
4.11. 3,7-Anhydro-1,2-dideoxy-D-glycero-D-galacto-oct-
1-enitol [b-anomer] and 3,7-anhydro-1,2-dideoxy-D-
glycero-D-talo-oct-1-enitol [a-anomer] 15
To a stirred solution of 16 (0.259 g, 0.604 mmol) in
acetone (6 mL) was added 2,2-dimethoxypropane
(1.5 mL) and p-toluenesulfonic acid (0.003 g). After
stirring overnight, two drops of triethylamine were
added and the solvents evaporated. Chromatography
of the residue (petroleum ether/ethyl acetate 4:1)
gave 0.176 g of 17 (0.375 mmol, 62%, white solid) as
To a solution of 14 (3.102 g, 8.660 mmol) in dry metha-
nol(50 mL) was added sodium methoxide (NaOMe) un-
tilpH 9 was reached. The reaction mixture was stirred
for severalhours untilTLC control(dichol romethane/
methanol10:1) confirmed compelte reaction. After neu-
tralization with Amberlite IR 120 H+, the solution was
filtered and the solvent evaporated to give 1.645 g of
15 (8.649 mmol, 100%, colourless syrup) as an insepar-
able anomeric mixture (a:b ꢀ 0.4:1.0). C8H14O5, 190.2;
MALDI-TOF: [M+Na]+: 213, [M+K]+: 229; b-anomer:
1H NMR (500 MHz, (CD3)2SO): d = 3.03–3.06 (m,
1H, H-7), 3.28–3.47, 3.57–3.69 (2 · m, 10H, H-4, H-5,
H-6, H-8a/b), 3.82 (dd, 1H, H-3), 4.29–4.75 (br m, 8H,
OH), 5.09 (ddd ꢁ dt, 1H, H-1b), 5.20–5.29 (m, 3H,
H-1a, H-1b), 5.84–5.95 (m, 2H, H-2) ppm. 13C NMR
(100 MHz, (CD3)2SO): d = 61.68 (1C, C-8), 67.20,
71.79, 74.75, 78.92, 81.06 (5C, C-3, C-4, C-5, C-6,
C-7), 115.73 (1C, C-1), 137.07 (1C, C-2) ppm.
pure b-anomer. Mp (solid after chromatography): 87–
20
90 ꢁC; ½aŠ ¼ À8:0 (c 0.5, EtOAc); C27H36O5Si,
546
1
468.7; MALDI-TOF: [M+Na]+: 492, [M+K]+: 508; H
NMR (400 MHz, C6D6): d = 1.18 (s, 9H, tert-butyl),
1.26, 1.50 (2 · s, 2 · 3H, 2 · Me), 2.21 (br s, 1H,
6-OH), 3.16 (m, 1H, H-7, J6,7 = 9.2, J7,8a = 3.8, J7,8b
=
4.6 Hz), 3.72 (dd, 1H, H-4, J4,5 = 2.3 Hz), 3.75
(ddd ꢁ dt, 1H, H-3, J2,3 = 5.9 Hz), 3.86–3.93 (m, 2H,
H-5, H-6, J4,5 = 2.3, J6,7 = 9.2 Hz), 4.02–4.09 (m, 2H,
H-8a/b, J7,8a = 3.8, J7,8b = 4.6, J8a,8b = 10.8 Hz), 5.12
(ddd ꢁ dt, 1H, H-1b, J1a,1b = 1.5, J1b,2 = 10.7 Hz), 5.33
(ddd ꢁ dt, 1H, H-1a, J1a,1b = 1.5, J1a,2 = 17.3 Hz), 6.09
(ddd, 1H, H-2, J1a,2 = 17.3, J1b,2 = 10.7, J2,3 = 5.9 Hz),
7.19–7.26, 7.83–7.88 (2 · m, 10H, Ar) ppm. 13C NMR
(100 MHz, C6D6): d = 26.64 (1C, Me), 27.08 (3C, tert-
butyl), 28.53 (1C, Me), 64.95 (1C, C-8), 70.97 (1C,
C-6), 76.55 (1C, C-4), 77.38 (1C, C-3), 78.64 (1C, C-7),
80.63 (1C, C-5), 109.56 (1C, CMe2), 116.54 (1C, C-1),
128.16–136.22 (13C, C-2, Ar) ppm; Anal. Calcd for
C27H36O5Si, 468.7: C, 69.18; H, 7.76. Found: C, 68.75;
H, 7.75.
4.12. 3,7-Anhydro-8-O-tert-butyldiphenylsilyl-1,2-dide-
oxy-D-glycero-D-galacto-oct-1-enitol [b-anomer] and 3,7-
anhydro-8-O-tert-butyldiphenylsilyl-1,2-dideoxy-D-
glycero-D-talo-oct-1-enitol [a-anomer] 16
To a solution of 15 (1.662 g, 8.738 mmol) in DMF
(50 mL) was added imidazole (0.654 g, 9.606 mmol)
and
tert-butyldiphenylsilyl
chloride
(2.46 mL,
4.14. (3,7-Anhydro-8-O-tert-butyldiphenylsilyl-1,2,6-tri-
deoxy-4,5-di-O-isopropylidene-D-glycero-D-galacto-oct-
1-enitol-6-yl)-20,30,40,60-tetra-O-benzyl-a-D-glucopyrano-
side 18
9.612 mmol). The reaction mixture was stirred for
3 days with two further additions of tert-butyldiphenyl-
silyl chloride (0.80 mL, 0.60 mL, respectively). After
TLC controlconfirmed the disappearance of the start-
ing material, the reaction was quenched with water.
Acetone was then added in order to precipitate the
imidazolium salts. After filtration and evaporation,
the residue was purified by column chromatography
(petroleum ether/ethyl acetate 1:2) to give 2.996 g of
16 (6.989 mmol, 80%, colourless syrup) as an insepar-
able anomeric mixture (a:b ꢀ 0.4:1.0). C24H32O5Si,
428.7; MALDI-TOF: [M+Na]+: 452, [M+K]+: 467;
b-anomer: 1H NMR (500 MHz, CDCl3): d = 1.06 (s,
9H, tert-butyl), 2.87–3.05 (br s, 3H, 3 · OH), 3.37–
To a solution of 17 (96 mg, 205 lmol) in dry dichloro-
methane (5 mL) with molecular sieves was added a
solution of TMSOTf in dichloromethane (170 lL,
concentration approx. 0.223 M, 38 lmol) at 0 ꢁC under
an argon atmosphere. Afterwards, a solution of 10
(168 mg, 248 lmol) in dichloromethane (4 mL) was
added at 0 ꢁC. The reaction mixture was stirred over-
night and terminated by the addition of three drops of
triethylamine. Evaporation of the solvent and chroma-
tography of the residue (petroleum ether/ethyl acetate
3.41 (m, 1H, H-7, J6,7 = 9.5, J7,8a = 4.7, J7,8b
=
12:1) gave 108 mg 18 (109 lmol, 53%) as a yellow syrup.
20
5.7 Hz), 3.63 (dd, 1H, H-5, J4,5 = 3.2, J5,6 = 9.1 Hz),
3.87–3.90, 4.01–4.02 (2 · m, 3H, H-3, H-4, H-6,
J2,3 = 4.7, J4,5 = 3.2, J5,6 = 9.1, J6,7 = 9.5 Hz), 3.93
(dd, 1H, H-8a, J7,8a = 4.7, J8a,8b = 10.7 Hz), 3.98 (dd,
1H, H-8b, J7,8b = 5.7, J8a,8b = 10.7 Hz), 5.29 (ddd ꢁ dt,
1H, H-1a, J1a,1b = 1.5, J1a,2 = 17.3 Hz), 5.39 (ddd ꢁ
dt, 1H, H-1b, J1a,1b = 1.5, J1b,2 = 10.7 Hz), 5.87 (ddd,
1H, H-2, J1a,2 = 17.3, J1b,2 = 10.7, J2,3 = 4.7 Hz), 7.38–
7.45, 7.66–7.70 (2 · m, 10H, Ar) ppm. 13C NMR
(100 MHz, CDCl3): d = 26.79 (4C, tert-butyl), 65.28
(1C, C-8), 70.54, 71.00, 75.31, 77.92, 78.23 (5C, C-3,
C-4, C-5, C-6, C-7), 117.47 (1C, C-1), 127.80, 129.89,
132.75, 132.78, 134.06, 135.55 (12C, Ar), 134.06 (1C,
C-2) ppm.
½aŠ ¼ þ36:5 (c 0.5, EtOAc); C61H70O10Si, 991.4;
546
MALDI-TOF: [M+Na]+: 1014, [M+K]+: 1030; 1H
NMR (500 MHz, C6D6): d = 1.24 (s, 9H, tert-butyl),
1.40, 1.53 (2 · s, 2 · 3H, 2Me), 3.32 (ddd, 1H, H-7,
J6,7 = 9.1, J7,8a = 2.2, J7,8b = 4.4 Hz), 3.54 (d, 1H, H-
60b, J6 a,6 b = 10.4 Hz), 3.61 (dd, 1H, H-20, J1 ,2 = 3.5,
0
0
0
0
J2 ,3 = 9.8 Hz), 3.69–3.74 (m, 3H, H-3, H-5, H-60a,
0
0
J2,3 = 5.9, J6 a,6 b = 10.4 Hz), 3.98–4.03 (m, 2H, H-40,
0
0
H-50), 4.14–4.30 (m, 6H, H-30, H-8a/b, H-6, H-4,
0
0
OCH2, J6,7 = 9.1, J7,8a = 2.2, J7,8b = 4.4, J2 ,3 = 9.8 Hz),
4.43, 4.58, 4.70, 4.71, 4.91, 5.00, 5.09 (7 · d, 7H, OCH2),
5.15 (d, 1H, H-1b, J1b,2 = 10.4 Hz), 5.34 (d, 1H, H-1a,
J1a,2 = 17.0 Hz), 5.90 (d, 1H, H-10, J1 ,2 = 3.5 Hz),
6.07–6.13 (m, 1H, H-2, J1a,2 = 17.0, J1b,2 = 10.4,
0
0

S. Ju¨rs, J. Thiem / Tetrahedron: Asymmetry 16 (2005) 1631–1638
1637
20
546
J2,3 = 5.9 Hz), 7.08–7.42, 7.87–7.95 (2 · m, 30H, Ar)
ppm. 13C NMR (100 MHz, C6D6): d = 26.62 (1C, Me),
27.29 (3C, tert-butyl), 28.26 (1C, Me), 64.48 (1C, C-8),
69.21 (1C, C-60), 72.03 (1C, C-50), 73.13 (1C, C-4),
73.27, 73.61, 75.40, 75.57 (4C, OCH2), 76.71, 77.30
(2C, C-3, C-5), 78.34, 78.47 (2C, C-7, C-40), 80.32 (1C,
C-6), 81.07 (1C, C-20), 82.24 (1C, C-30), 95.84 (1C,
C-10), 109.72 (1C, CMe2), 116.67 (1C, C-1), 127.52–
128.57, 129.90, 129.99, 135.31, 136.08, 136.47 (37C,
C-2, Ar) ppm.
½aŠ ¼ þ56:0 (c 0.25, EtOAc); C52H58O12S, 907.2;
MALDI-TOF: [M+Na]+: 930, [M+K]+: 946; H NMR
(400 MHz, C6D6): d = 1.17, 1.39 (2 · s, 2 · 3H,
2 · Me), 1.78 (s, 3H, Ts–Me), 3.26 (ddd, 1H, H-7,
J6,7 = 9.4, J7,8a = 2.3, J7,8b = 5.4 Hz), 3.54–3.58 (m, 1H,
H-3, J2,3 = 5.9, J3,4 = 2.4 Hz), 3.59–3.62 (m, 2H, H-4,
1
H-20, J3,4 = 2.4, J1 ,2 = 3.8, J2 ,3 = 9.4 Hz), 3.94–4.04
(m, 4H, H-6, H-40, H-60a/b, J5,6 = 6.4, J6,7 = 9.4,
0
0
0
0
J3 ,4 = J4 ,5 = 9.4 Hz), 4.11–4.17 (m, 2H, H-5, H-50,
0
0
0
0
J5,6 = 6.4, J4 ,5 = 9.4 Hz), 4.22 (dd ꢁ t, 1H, H-30,
0
0
0
0
0
0
J2 ,3 = J3 ,4 = 9.4 Hz), 4.34 (dd, 1H, H-8b, J7,8b = 5.4,
J8a,8b = 10.5 Hz), 4.38 (1, H, OCH2), 4.47–4.52 (m, 2H,
H-8a, OCH2, J7,8a = 2.3, J8a,8b = 10.5 Hz), 4.58, 4.67,
4.75, 4.95 (4 · d, 4H, OCH2), 4.99–5.05 (m, 2H, H-1b,
OCH2, J1a,1b = 1.5, J1b,2 = 10.5 Hz), 5.10 (d, 1H,
OCH2), 5.18 (ddd ꢁ dt, 1H, H-1a, J1a,1b = 1.5,
4.15. (3,7-Anhydro-1,2,6-trideoxy-4,5-di-O-isopropylid-
ene-D-glycero-D-galacto-oct-1-enitol-6-yl)-20,30,40,60-
tetra-O-benzyl-a-D-glucopyranoside 19
To a solution of 18 (157 mg, 158 lmol) in THF (7 mL)
was added a solution of tetrabutylammonium fluoride
in THF (0.19 mL, 1 M, 190 lmol) at 0 ꢁC. The solution
was stirred at room temperature for 4 days. Evaporation
of the solvent and chromatography of the residue
J1a,2 = 17.0 Hz), 5.80 (d, 1H, H-10, J1 ,2 = 3.8 Hz),
5.87–5.96 (m, 1H, H-2, J2,3 = 5.9 Hz), 6.63 (d, 2H, Ar),
7.06–7.21 (m, 12H, Ar), 7.33, 7.41 (2 · d, 8H, Ar),
7.82 (d, 2H, Ar) ppm. 13C NMR (100 MHz, C6D6):
d = 21.14 (1C, Ts–Me), 26.39, 28.10 (2C, 2 · Me),
69.45 (1C, C-60), 69.82 (1C, C-8), 72.33 (1C, C-50),
73.26 (1C, C-6), 73.41, 73.62 (2C, OCH2), 75.37 (1C,
OCH2), 75.55 (1C, C-7), 75.66 (1C, OCH2), 76.41,
80.85 (2C, C-4, C-20), 77.25 (1C, C-3), 78.43 (1C, C-
40), 79.62 (1C, C-5), 82.20 (1C, C-30), 96.22 (1C, C-10),
116.94 (1C, C-1), 127.64–128.73, 129.88 (30C, Ar),
134.40 (1C, C-2) ppm.
0
0
(petroleum ether/ethyl acetate 4:1) gave 73 mg of 19
20
546
(97 lmol, 61%) as a yellowish syrup. ½aŠ ¼ þ66:0 (c
0.5, EtOAc); C45H52O10, 753.0; MALDI-TOF:
[M+Na]+: 776, [M+K]+: 792; 1H NMR (500 MHz,
C6D6): d = 1.22, 1.50 (2 · s, 2 · 3H, 2 · Me), 2.20 (br
s, 1H, 8-OH), 3.12 (ddd, 1H, H-7, J6,7 = 9.5,
J7,8a = 2.5, J7,8b = 3.8 Hz), 3.62 (dd, 1H, H-20,
0
0
0
0
J1 ,2 = 3.8, J2 ,3 = 9.8 Hz), 3.68–3.70 (m, 2H, H-3,
H-4, J2,3 = 6.1 Hz), 3.75–3.79 (m, 3H, H-40, H-60a/b,
0
0
0
0
0
0
0
0
J3 ,4 = J4 ,5 = 9.8, J5 ,6 a = J5 ,6 b = 3.2 Hz), 3.89 (br d,
1H, H-8b, J7,8b = 3.8 Hz), 3.95 (br d, 1H, H-8a,
4.17. (3,7-Anhydro-8-bromo-1,2,6,8-tetradeoxy-4,5-di-
O-isopropylidene-D-glycero-D-galacto-oct-1-enitol-6-yl)-
20,30,40,60-tetra-O-benzyl-a-D-glucopyranoside 21
J7,8a = 2.5 Hz), 4.14 (ddd ꢁ dt, 1H, H-50, J4 ,5 = 9.8,
0
0
J5 ,6 a = J5 ,6 b = 3.2 Hz), 4.18–4.22 (m, 2H, H-5, H-30,
0
0
0
0
0
0
0
0
J5,6 = 6.9, J2 ,3 = J3 ,4 = 9.8 Hz), 4.26 (dd, 1H, H-6,
J5,6 = 6.9, J6,7 = 9.5 Hz), 4.35, 4.43, 4.59, 4.63, 4.77,
4.87, 4.95 (7 · d, 7H, OCH2), 5.07–5.10 (m, 2H,
OCH2, H-1b, J1a,1b = 1.3, J1b,2 = 10.4 Hz), 5.23 (d, 1H,
H-1a, J1a,1b = 1.3, J1a,2 = 17.3 Hz), 5.88 (d, 1H, H-10,
A solution of 20 (52 mg, 57 lmol) and NaBr (59 mg,
573 lmol) in DMF (4 mL) was heated to 70 ꢁC and stir-
red overnight. After evaporation of the solvent, the res-
idue was dissolved in dichloromethane and the solution
filtrated. Evaporation of the solvent yielded 59 mg of the
raw product 21 accompanied by sodium tosylate. The
residue was directly used without further purification
for the subsequent elimination.
0
0
J1 ,2 = 3.8 Hz), 6.04–6.11 (m, 1H, H-2, J1a,2 = 17.3,
J1b,2 = 10.4, J2,3 = 6.1 Hz), 7.06–7.45 (m, 20H, Ar)
ppm. 13C NMR (100 MHz, C6D6): d = 26.58, 28.30
(2C, 2 · Me), 62.51 (1C, C-8), 69.52 (1C, C-60), 71.98
(1C, C-50), 73.08 (1C, OCH2), 73.32 (1C, C-6), 73.55
(1C, OCH2), 75.31, 75.63 (2C, OCH2), 76.82, 77.70,
77.95, 78.53 (4C, C-3, C-4, C-7, C-40), 80.42, 80.90,
82.38 (3C, C-5, C-20, C-30), 96.14 (1C, C-10), 109.70
(1C, CMe2), 117.00 (1C, C-1), 127.55–128.60, 139.27,
139.86 (24C, Ar), 135.05 (1C, C-2) ppm.
4.18. (3,7-Anhydro-1,2,6,8-tetradeoxy-4,5-di-O-isoprop-
ylidene-D-galacto-octo-1,7-dienitol-6-yl)-20,30,40,60-tetra-
O-benzyl-a-D-glucopyranoside 22
To a solution of raw product 21 dissolved in pyridine
(3 mL), was added silver fluoride (47 mg, 370 lmol).
The solution was stirred under light exclusion at room
temperature. On the next day, a second portion of silver
fluoride was added and stirring continued for 1 day until
TLC showed complete conversion of bromide 21. After
filtration, co-distillation with toluene and evaporation of
the solvents chromatography of the residue (petroleum
4.16. [3,7-Anhydro-8-O-(4-toluenesulfonyl)-1,2,6-tride-
oxy-4,5-di-O-isopropylidene-D-glycero-D-galacto-oct-1-
enitol-6-yl]-20,30,40,60-tetra-O-benzyl-a-D-glucopyrano-
side 20
To a solution of 19 (63 mg, 84 lmol) in dry pyridine
(4 mL) was added a catalytic amount of 4-dimethylami-
nopyridine (DMAP) and tosylcohrlide (19 mg,
100 lmol). The solution was stirred at room tempera-
ture for 5 days with severalextra additions of tosylchlo-
ride untilthe alrgest part of starting materialhad
reacted. Evaporation of the solvent and chromatogra-
phy of the residue (petroleum ether/ethyl acetate 6:1)
gave 63 mg of 20 (69 lmol, 83%) as a colourless syrup.
ether/ethylacetate 10:1) gave 9 mg of
22 (12.2
lmol, 21% via two steps) as a colourless syrup.
20
D
½aŠ ¼ þ14:9 (c 0.5, CHCl3); C45H50O9, 735.0; MALDI-
TOF: [M+Na]+: 758, [M+K]+: 774; 1H NMR
(400 MHz, C6D6): d = 1.17, 1.50 (2 · s, 2 · 3H,
2 · Me), 3.51 (dd, 1H, H-20, J1 ,2 = 3.7, J2 ,3 = 9.4 Hz),
0
0
0
0
3.67 (dd, 1H, H-60b, J5 ,6 b = 1.8, J6 a,6 b = 10.7 Hz),
0
0
0
0
3.78 (dd, 1H, H-60a, J5 ,6 a = 3.6, J6 a,6 b = 10.7 Hz),
0
0
0
0
3.90 (dd ꢁ t, 1H, H-40, J3 ,4 = J4 ,5 = 9.4 Hz), 4.09 (dd,
0
0
0
0

1638
S. Ju¨rs, J. Thiem / Tetrahedron: Asymmetry 16 (2005) 1631–1638
1H, H-4, J3,4 = 1.5, J4,5 = 7.4 Hz), 4.14–4.20 (m, 2H, H-30,
C-2), 99.20 (1C, C-10), 127.21–128.88 (25C, C-6, Ar),
134.10 (1C, C-5) ppm.
H-50, J2 ,3 = J3 ,4 = J4 ,5 = 9.4, J5 ,6 a = 3.6, J5 ,6 b
0
0
0
0
0
0
0
0
0
0
=
1.8 Hz), 4.27–4.37 (m, 5H, H-5, H-6, H-8b, OCH2,
J4,5 = 7.4 Hz), 4.45, 4.53, 4.67 (3 · d, 3H, OCH2), 4.76
(s, 1H, H-8a), 4.83 (d, 1H, OCH2), 4.94–4.98 (m, 2H,
Acknowledgements
H-10, OCH2, J1 ,2 = 3.7 Hz), 5.00 (dd, 1H, H-3,
J2,3 = 6.6, J3,4 = 1.5 Hz), 5.10 (ddd ꢁ dt, 1H, H-1b,
J1a,1b = 1.5, J1b,2 = 10.4 Hz), 5.37 (ddd ꢁ dt, 1H, H-1a,
J1a,1b = 1.5, J1a,2 = 17.3 Hz), 6.10–6.19 (m, 1H, H-2,
J1a,2 = 17.3, J1b,2 = 10.4, J2,3 = 6.6 Hz), 7.03–7.35 (m,
20H, Ar) ppm. 13C NMR (100 MHz, C6D6): d = 24.72,
26.76 (2C, 2 · Me), 69.12 (1C, C-60), 72.16 (1C, C-50),
73.40, 74.43, 74.90 (3C, C-3, C-5, C-6), 73.46, 73.59
(2C, OCH2), 75.24, 75.56 (2C, OCH2), 75.72 (1C, C-4),
78.42 (1C, C-40), 81.07 (1C, C-20), 82.42 (1C, C-30),
92.62 (1C, C-8), 96.78 (1C, C-10), 117.58 (1C, C-1),
127.58–128.70 (24C, Ar), 135.13 (1C, C-2) ppm.
0
0
Support of this work by the Deutsche Forschungsge-
meinschaft (GRK 464) and the Fonds der Chemischen
Industrie is gratefully acknowledged.
References
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recovered 22 (9.5 lmol). C45H50O9, 735.0; MALDI-
20
TOF: [M+Na]+: 757; ½aŠ ¼ þ53:0 (c 0.1, CHCl3);
546
m (film/cmÀ1): 1719 (C@O); 1H NMR (500 MHz,
C6D6): d = 1.20, 1.46 (2 · s, 2 · 3H, Me), 1.56–1.70 (m,
2H, H-7a/b), 2.20 (ddd, 1H, H-8b, J8a,8b = 13.6 Hz),
2.41 (ddd, 1H, H-8a, J8a,8b = 13.6 Hz), 3.56–3.59 (m,
2H, H-20, H-60b, J1 ,2 = 3.8, J2 ,3 = 9.5, J5 ,6 b = 1.5,
0
0
0
0
0
0
J6 a,6 b = 10.8 Hz), 3.67–3.73 (m, 2H, H-40, H-60a,
0
0
0
0
0
0
0
0
0
0
J3 ,4 = J4 ,5 = 9.5, J5 ,6 a = 4.7, J6 a,6 b = 10.8 Hz), 4.09–
4.13 (ddd, 1H, H-50, J4 ,5 = 9.5, J5 ,6 a = 4.7,
0
0
0
0
10. Schmidt, R. R.; Michel, J.; Roos, M. Liebigs Ann. Chem.
1984, 22, 1343–1357.
0
0
J5 ,6 b = 1.5 Hz), 4.16 (d, 1H, H-2, J2,3 = 8.9 Hz), 4.29
(dd ꢁ t, 1H, H-30, J2 ,3 = J3 ,4 = 9.5 Hz), 4.33 (d, 1H,
OCH2), 4.35–4.40 (m, 2H, H-3, OCH2, J2,3 = 8.9,
J3,4 = 5.2 Hz), 4.42–4.44 (m, 1H, H-4, J3,4 = 5.2,
J4,5 = 6.3, J4,6 = 1.8 Hz), 4.49, 4.60, 4.62, 4.68, 4.89,
4.95 (6 · d, 6H, OCH2), 5.05 (d, 1H, H-10,
0
0
0
0
11. Large amounts of AgF were required to effect complete
elimination leading in turn to significant losses of product
during workup due to adsorption on silver salts.
12. Paquette, L. A.; Friedrich, D.; Rogers, R. D. J. Org.
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14. Nomenclature of Carbohydrates (Recommendations
1996), Carbohydr. Res. 1997, 297, 1–92.
15. Lemieux, R. U. Methods Carbohydr. Chem. 1963, 32, 221–
222.
16. Levene, P. A.; Tipson, R. S. J. Biol. Chem. 1931, 90, 89–
98.
0
0
J1 ,2 = 3.8 Hz), 5.37–5.45 (m, 1H, H-6, J4,6 = 1.8,
J5,6 = 11.2 Hz), 5.60 (ddd, 1H, H-5, J4,5 = 6.3,
J5,6 = 11.2 Hz), 6.96–7.36, 7.48–7.51 (2 · m, 20H, Ar)
ppm. 13C NMR (100 MHz, C6D6): d = 24.77 (1C, C-7),
26.35, 27.85 (2C, 2 · Me), 44.20 (1C, C-8), 69.70 (1C,
C-60), 71.72 (1C, C-50), 71.96, 73.52 (2C, OCH2), 73.87
(1C, C-4), 75.02, 75.60 (2C, OCH2), 78.16 (2C, C-3,
C-40), 80.76 (1C, C-20), 82.17 (1C, C-30), 82.78 (1C,