Dibutyl tin oxide mediated, regioselective alkylation and acylation of siloxane protected glycopyranosides

Article abstract of DOI:10.1055/s-1999-3569

Treatment of alkyl and aryl 4,6-O-(1,1,3,3-tetraisopropyl-1,3- disiloxane-1,3-diyl)-D-glycopyranosides 2 with dibutyltin oxide followed by benzoyl chloride, benzyl bromide and allyl bromide afforded regioselectively the corresponding mono acylated and alkylated glycosides. The regioselective acylation of the stannylene intermediates is inverted as compared to the direct acylation of 2. Regioselective alkylations of 2 proceeded without affecting the siloxane residue.

Full text of DOI:10.1055/s-1999-3569

PAPER
1661
Dibutyl Tin Oxide Mediated, Regioselective Alkylation and Acylation of
Siloxane Protected Glycopyranosides
Thomas Ziegler,* Ralf Dettmann, Jaroslaw Grabowski
Institute of Organic Chemistry, University of Cologne, Greinstraße 4, D-50939 Cologne, Germany
Fax +49(221)4705057; E-mail: thomas.ziegler@uni-koeln.de
Received 24 April 1999
lowed by Pd-catalyzed decarboxylative rearrangement of
the acylated intermediates to the corresponding allylated
glycosides.5 Therefore, it would be highly desirable to
find reaction conditions which allow for the selective
Abstract: Treatment of alkyl and aryl 4,6-O-(1,1,3,3-tetraisopro-
pyl-1,3-disiloxane-1,3-diyl)-D-glycopyranosides 2 with dibutyltin
oxide followed by benzoyl chloride, benzyl bromide and allyl bro-
mide afforded regioselectively the corresponding mono acylated
and alkylated glycosides. The regioselective acylation of the stan- alkylation of 4,6-TIPS protected glycopyranosides with-
nylene intermediates is inverted as compared to the direct acylation
of 2. Regioselective alkylations of 2 proceeded without affecting
the siloxane residue.
out affecting the TIPS group. In this paper, we now
present a flexible procedure based on dibutyl stannylene
derivatives of TIPS protected D-gluco-, D-manno-, and D-
galactopyranosides which allows the regioselective alky-
Key words: protecting groups, silylation, siloxanes, glycopyrano-
sides, saccharides, alkylation, acylation, benzoylation
lation and acylation of 4,6-TIPS protected sugars.
The acylation and alkylation of dibutyl stannylene inter-
mediates of simple glycopyranosides is a well established
One of the most remarkable developments in protecting
procedure for the regioselective protection of sugars.8,9
group chemistry of carbohydrates in the past decades are
Although examples for the regioselective manipulation of
without any doubt the silyl ether groups. Due to the viable
functional groups of carbohydrates via tin intermediates
stability and the ease of cleavage of silyl ether groups vir-
are abundant, there is only one single example described
tually under all reaction conditions simply by varying the
in the literature where the stannylation procedure was
substitution patterns at the silicon atoms makes silyl ether
protecting groups almost ideal for saccharide syntheses.
In this respect, the bifunctional 1,1,3,3-tetraisopropyl-1,3-
used in combination with the TIPS group. Here, a regiose-
lective stannylene mediated 3-O benzylation of the b-
(1→4)-linked 4,6-O-benzylidene-D-glucopyranosyl side
disiloxane-1,3-diyl (TIPS) group which was introduced
chain of 2,3-TIPS protected levoglucosene was performed
by Markiewicz in 1979 for the synchronous protection of
thus demonstrating that the TIPS group remains uneffect-
contiguous hydroxyls in nucleosides1 appears to be an es-
ed by intermediate stannylene derivatives.10
pecially useful protecting group. In general, otherwise un-
For stannylations and regioselective acylations and alky-
protected pentofuranosides and hexopyranosides, can be
lations, we chose 4,6-O-(1,1,3,3-tetraisopropyl-1,3-disi-
selectively blocked by the TIPS group at hydroxy groups
3 and 5 of furanosides and 4 and 6 of pyranosides.2 Fur-
thermore, 3,5-TIPS protected furanosides and 4,6-TIPS
protected pyranosides are easily rearranged to the corre-
sponding 2,3 protected and 3,4 protected counterparts by
simple treatment with acid.2-6 Thus, the TIPS group may
be regarded as a “silyl” equivalent to the classical acetal
protecting groups for carbohydrates which, in addition, al-
lows for the protection of trans-diequatorial hydroxyl
groups as well. Another useful feature of 4,6-TIPS pro-
tected pyranosides is the regioselective acylation of posi-
tion 2 of the latter and the regioselective ring opening with
hydrofluoric acid or glycosyl fluorides that makes protect-
ing group strategies using TIPS groups highly flexible and
advantageous for oligosaccharide synthesis.2,7
loxane-1,3-diyl)-glycopyranosides 2 in the D-galacto, D-
gluco and D-manno series (Scheme 1). TIPS protected
glycosides 2b,11 2c,12 and 2d13 were prepared from the
corresponding glycosides 1 using 1,3-dichloro-1,1,3,3-
tetraisopropyl-1,3-disiloxane and imidazole as previously
described. For the preparation of phenyl 1-thiogalactoside
2a this procedure failed as was previously encountered for
other galactosides.12 Therefore, a modified procedure14
using pyridine/DMF mixtures as the solvent was applied
here. Thus, phenyl 1-thio-b-D-galactopyranoside 1a was
converted into the corresponding TIPS protected galacto-
side 2a in 79% yield.
Next, benzoylation of TIPS-protected glycosides 2 was
performed either by treatment of 2 directly with benzoyl
chloride in pyridine (Table, Procedure A) or by first stan-
nylation followed by benzoylation with benzoyl chloride
(Table, Procedure B). As was expected from previous
acylations of 4,6-TIPS protected glycosides2-7 direct ben-
zoylations afforded solely the corresponding 2-O-benzoy-
lated glycosides 3. In contrast, when the intermediate
stannylene derivative of galactoside 2a was benzoylated
an almost complete inversion of the regioselectivity was
However, a major draw back of TIPS protected pyrano-
sides lies in the incompatibility of TIPS with conditions
which are commonly necessary for the introduction of
benzyl and allyl protecting groups (i.e. destruction of the
siloxane moiety during alkylation of TIPS protected sug-
ars under strongly basic conditions5). Solely, allyl groups
have been successfully introduced into TIPS-protected
glycopyranosides by initial allyloxycarbonylation fol-
Synthesis 1999, No. 9, 1661–1665 ISSN 0039-7881 © Thieme Stuttgart · New York

1662
T. Ziegler et al.
PAPER
Si
Si
Si
OH
O
O
O
O
O
HO
HO
O
O
O
[ClSi(i-prop)2]2O
O
2a
2b
2c
Si
HO
Si
BzO
Si
O
O
O
O
SPh
SPh
SPh
pyridine-DMF 4:1
0°C, 2 h, 79%
SPh
HO
HO
BzO
HO
HO
1a
3a
4a
2a
Si
Si
Si
O
O
O
OH
O
O
O
Si
Si
Si
ref. 11
O
O
O
HO
HO
O
BzO
O
O
O
HO
HO
HO
OCH3
HO
OCH3
BzO
HO
OCH3
OCH3
4b
3b
1b
2b
Si
Si
Si
O
O
O
O
OH
O
O
OH
OH
O
Si
O
Si
OBz
O
ref. 12, 13
Si
OH
O
O
O
BzO
HO
HO
O
HO
HO
3c
OCH3
4c
OCH3
R
R
1c R = OCH3
1d R = S(CH2)6CH3
2c R = OCH3
2d R =
S(CH2)6CH3
For reaction conditions and yield of product(s), see Table
Scheme 2
Scheme 1
terpart (experimental data are not given). A similar case
has been previously found as well.10 All alkylation posi-
tions were unambigously assigned as outlined above by
acetylation of compounds 5, 7, and 9 followed by inspec-
tion of the NMR spectra of the thus obtained products 6,
8, and 10, respectively. Furthermore, octyl 1-thio-manno-
side 11 was used as glycosyl acceptor for coupling with
ethyl 2,3,4,6-tetra-O-benzyl-1-thio-a-D-galactopyrano-
side16 12 under promotion by methyl trifluoromethane-
sulfonate to give the corresponding a-(1→2)-linked dis-
accharide 13, related to the GPI-anchor of Trypanosoma
brucei.13
observed. Thus, the corresponding 3-O-benzoylgalacto-
side 4a (77%) was formed as the main product (Scheme
2). Benzoylation of the stannylene derivatives of gluco-
side 2b and mannoside 2c gave mixtures of the 2-O- and
3-O-benzoylated products which, however, were easily
separated by chromatography. The respective position of
benzoylation was unambigously assigned for all benzoy-
1
lation products 3 and 4 by simple inspection of the H
NMR spectra of compounds 3 and 4 which showed a sig-
nificant downfield shift for H-2 and H-3, respectively
when a benzoyl group was present at this position.
Obviously, the regioselectivity of alkylations of stan-
nylene intermediates of TIPS-protected glycosides is
strongly governed by the relative configuration of hy-
droxy groups at position 2 and 3 whereas benzoylations
depend more on steric factors due to the sterically de-
In contrast to the benzoylations of stannylene intermedi-
ates of TIPS protected glycosides 2, alkylations (i.e. ben-
zylation and allylation) proceeded with high selectivity in
all cases (Scheme 3). All reactions proceeded smoothly
and no decomposition of the TIPS group was observed.
Treatment of glucoside 2b with dibutyl tin oxide followed
by benzyl bromide afforded the 2-O-benzyl-glucoside 5 in
91% yield. Therefore, a significantly higher regioselectiv-
ity compared to the respective benzoylation of 2b was
found in this case since the latter gave a 2:1 mixture of the
corresponding 2-O-benzoyl- 3b and 3-O-benzoylgluco-
side 4b (cf. Table). In contrast, both mannosides 2c and
2d afforded the corresponding 3-O-alkylated products 7,
9 and 11 exclusively upon benzylation or allylation. This
regioselectivity is surprising since the sterically more de-
manding position reacted here (i.e. position 3). It should
Table Benzoylation of Glycopyranosides 2a–c
Sub-
Benzoylation
Product(s)
strate Procedurea
3
Yield (%)
4
Yield (%)
2a
2a
2b
2b
2c
2c
A
B
A
B
A
B
3a
3a
3b
3b
3c
3c
77
8
89
62
67
69
4a
4a
4b
4b
4c
4c
0
77
0
31
0
31
be also noted that all attempts to benzylate compound 2c a A: BzCl in pyridine. Procedure A corresponds to the General Proce-
with benzyl bromide and silver oxide10,15 resulted in a 1:1
mixture of 7 and the corresponding 2-O-benzylated coun-
dure I described in the experimental part. B: 1. Bu2SnO; 2. BzCl. Pro-
cedure B corresponds to the General Procedure II described in the
experimental part.
Synthesis 1999, No. 9, 1661–1665 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Regioselective Alkylation and Acylation of Siloxane Protected Glycopyranosides
1663
Phenyl 4,6-O-(1,1,3,3-Tetraisopropyl-1,3-disiloxane-1,3-diyl)-1-
thio-b-D-galactopyranoside (2a)
Si
A solution of 1,3-dichloro-1,1,3,3-tetraisopropyl-1,3-disiloxane
(4.04 g, 12.8 mmol) and phenyl 1-thio-b-D-galactopyranoside17 (1a;
2.9 g, 10.65 mmol) in a mixture of DMF (23 mL) and pyridine (85
mL) was stirred at 0°C for 2 h, poured into H2O and extracted with
CH2Cl2. The combined extracts were washed with aq HCl and aq
NaHCO3 solution, dried and concentrated. Chromatography (elu-
ent: CCl4/acetone 10:1) of the residue afforded 2a (4.36 g, 79%);
[a]D20 –30 (c = 1.0, MeOH).
Si
1) Bu2SnO
2) BnBr
O
O
O
Ac2O
79%
O
O
Si
Si
2b
91%
O
O
O
AcO
HO
BnO
OCH3
BnO
OCH3
5
6
1H NMR (CDCl3): d = 3.66–3.56 (m, 3 H, H-2,3,5), 3.92–3.80 (m,
2 H, H-6a,6b), 4.25 (d, 1 H, J3,4 = 1.3 Hz, H-4), 4.46 (d, 1 H,
J1,2 = 9.2 Hz, H-1).
13C NMR (CDCl3): d = 59.3 (C-6), 68.2 (C-2), 69.2 (C-4), 74.9 (C-
3), 77.9 (C-5), 87.6 (C-1).
Si
Si
1) Bu2SnO
2) BnBr
O
O
Ac2O
O
OH
O
O
OAc
O
2c
Si
Si
91%
90%
O
BnO
O
BnO
7
8
OCH3
OCH3
Anal. Calcd for C24H42O6SSi2: C, 55.99; H, 8.22. Found C, 55.72;
H, 8.16.
Si
Si
1) Bu2SnO
2) AllylBr
O
O
Ac2O
91%
Benzoylation of Glycosides; General Procedure I
O
OH
O
O
OAc
O
2c
Si
Si
Benzoyl chloride (1.1 mmol) was added at 0°C to a solution of 2
(1.0 mmol) in pyridine (5 mL) and the mixture was stirred at r.t. un-
til all starting material was consumed. The mixture was poured into
H2O and extracted with CH2Cl2. The combined extracts were
washed with aq HCl and aq NaHCO3 solution, dried and concentrat-
ed. Chromatography (eluent: toluene/ethyl acetate 15:1) of the res-
idue afforded 3.
84%
O
O
AllylO
AllylO
9
10
OCH3
OCH3
OBn
O
BnO
BnO
Si
1) Bu2SnO
2) BnBr
SEt
O
O
OH
O
BnO
12
2d
Si
Benzoylation of Stannylene Intermediates; General Procedure
II
65%
O
BnO
49%
A solution of 2 (1.0 mmol) and Bu2SnO (1.1 mmol) in benzene (80
mL) was refluxed in a Dean–Stark apparatus for 16 h and concen-
trated to 40 ml. Benzoyl chloride (1.1 mmol) was added at 0°C and
strirring was continued at r.t. for 16 h. Workup as described in the
General Procedure I afforded 3 and 4, respectively.
11
S(CH2)7CH3
BnO
O
OBn
OBn
Si
O
Alkylation of Stannylene Intermediates; General Procedure III
A solution of 2 (1.0 mmol) and Bu2SnO (1.1 mmol) in benzene (80
mL) were treated as described in the General Procedure II. Benzyl
bromide (2.0 mmol) or allyl bromide (2.0 mmol), Bu4NI (1.0 mmol)
and 4 Å molecular sieves (1 g) were added and the mixture was re-
fluxed for 24 h. After cooling to r.t., the mixture was filtered
through a layer of Celite and concentrated. Chromatography (elu-
ent: toluene/ethyl acetate 10:1) of the residue afforded 5, 7, 9, and
11.
O
OBn
O
O
Si
O
BnO
13
S(CH2)7CH3
Scheme 3
Acetylation of Glycosides; General Procedure IV
Ac2O (2 mL) was added at r.t. to a solution of 5, 7, and 9 (0.2 mmol)
in pyridine (5 mL) and the mixture was stirred for 6 d at r.t. Workup
as described for the General Procedure I afforded 6, 8, and 10, re-
spectively.
manding TIPS group. Thus, regioselective alkylations of
TIPS protected glycosides via stannylene intermediates
may be regarded as a useful extension for TIPS-protected
glycosides in oligosaccharide synthesis.
Mps were determined with a Büchi apparatus and are uncorrected.
Optical rotations were measured with a Perkin-Elmer 241 polarim-
eter. 1H and 13C NMR spectra were recorded with a Bruker AC 300F
spectrometer at 300 MHz and 75.46 MHz, respectively. TLC was
performed on precoated silica gel plates (Merck, 60F254) using ap-
propriately adjusted mixtures of toluene/ethyl acetate. Detection of
the products was achieved by charring with 5% H2SO4 in MeOH.
Column chromatography was carried out on silica gel using col-
umns of different length (10-20 cm). Solvents were destilled prior
to use. Compounds 2b, 2c and 2d were prepared as previously de-
scribed.11-13
Phenyl 2-O-Benzoyl-4,6-O-(1,1,3,3-tetraisopropyl-1,3-disilox-
ane-1,3-diyl)-1-thio-b-D-galactopyranoside (3a)
Treatment of 2a (445 mg, 0.86 mmol) according to the General Pro-
cedure I afforded 3a (408 mg, 77%); [a]D20 –22.8 (c = 0.85, CHCl3).
1H NMR (CDCl3): d = 3.73–3.67 (m, 1 H, H-5), 3.79 (dd, 1 H, H-
3), 3.98–3.88 (m, 2 H, H-6a,6b), 4.32 (d, 1 H, J3,4 = 2.6 Hz, H-4),
4.78 (d, 1 H, J1,2 = 9.8 Hz, H-1), 5.14 (t, 1 H, J2,3 = 9.7 Hz, H-2).
13C NMR (CDCl3): d = 59.2 (C-6), 68.9 (C-4), 71.2 (C-2), 74.3 (C-
3), 77.8 (C-5), 85.3 (C-1).
Anal. Calcd for C31H46O7SSi2: C, 60.16; H, 7.49. Found C, 60.03;
H, 7.57.
Synthesis 1999, No. 9, 1661–1665 ISSN 0039-7881 © Thieme Stuttgart · New York

1664
T. Ziegler et al.
PAPER
Phenyl 3-O-Benzoyl-4,6-O-(1,1,3,3-tetraisopropyl-1,3-disilox-
ane-1,3-diyl)-1-thio-b-D-galactopyranoside (4a)
13C NMR (CDCl3) d = 61.4 (C-6), 64.7 (C-3), 70.3 (C-4), 73.4 (C-
5), 74.8 (C-2), 101.6 (C-1).
Treatment of 2a (266 mg, 0.52 mmol) according to the General Pro-
Anal. Calcd for C26H44O8Si2: C, 57.75; H, 8.20. Found C, 57.67; H,
8.18.
20
cedure II afforded 3a (24 mg, 8%) and 4a (250 mg, 77%); [a]D
12.9 (c = 1.1, CHCl3).
–
Methyl 2-O-Benzyl-4,6-O-(1,1,3,3-tetraisopropyl-1,3-disilox-
ane-1,3-diyl)-a-D-glucopyranoside (5)
1H NMR (CDCl3): d = 3.95–3.77 (m, 3 H, H-5,6a,6b), 4.06 (t, 1 H,
2,3 = 9.8 Hz, H-2), 4.55 (d, 1 H, H-4), 4.60 (d, 1 H, J1,2 = 9.5 Hz, H-
J
Treatment of 2b (437 mg, 1.0 mmol) according to the General Pro-
1),5.14 (t, 1 H, J3,4 = 2.8 Hz, H-3).
13C NMR (CDCl3): d = 59.1 (C-6), 66.4 (C-2), 66.7 (C-4), 77.1 (C-
3), 77.9 (C-5), 88.3 (C-1).
cedure III afforded 5 (480 mg, 91%); [a]D20 +47.8 (c = 1.1, CHCl3).
1H NMR (CDCl3) d = 3.51–3.47 (m, 1 H, H-5), 3.36 (dd, 1 H, H-2),
3.77 (t, 1 H, J3,4 = J4,5 = 9.2 Hz, H-4), 3.85 (dd, 1 H, J5,6b = 1.3 Hz,
H-6b), 3.94 (t, 1 H, J2,3 = J3,4 = 9.2 Hz, H-3), 4.11 (dd, 1 H,
Anal. Calcd for C31H46O7SSi2: C, 60.16; H, 7.49. Found C, 60.08;
H, 7.51.
J5,6a = 1.9 Hz, H-6a), 4.63 (d, 1 H, J1,2 = 4.0 Hz, H-1).
Methyl 2-O-Benzoyl-4,6-O-(1,1,3,3-tetraisopropyl-1,3-disilox-
ane-1,3-diyl)-a-D-glucopyranoside (3b)
13C NMR (CDCl3): d = 60.7 (C-6), 69.3 (C-4), 71.4 (C-5), 73.1 (C-
3), 79.9 (C-2), 98.0 (C-1).
Treatment of 2b (437 mg, 1.0 mmol) according to the General Pro-
Anal. Calcd for C26H46O7Si2: C, 59.28; H, 8.80. Found C, 59.05; H,
8.72.
cedure I afforded 3b (481mg, 89%); [a]D20 +72.5 (c = 1.7, CHCl3).
1H NMR (CDCl3): d = 3.95–3.77 (m, 3 H, H-5,6a,6b), 4.06 (t, 1 H,
Methyl 3-O-Acetyl-2-O-benzyl-4,6-O-(1,1,3,3-tetraisopropyl-
1,3-disiloxane-1,3-diyl)-a-D-glucopyranoside (6)
J2,3 = 9.8 Hz, H-2), 4.55 (d, 1 H, H-4), 4.60 (d, 1 H, J1,2 = 9.5 Hz, H-
1), 5.14 (t, 1 H, J3,4 = 2.8 Hz, H-3).
13C NMR (CDCl3): d = 59.1 (C-6), 66.4 (C-2), 66.7 (C-4), 77.1 (C-
3), 77.9 (C-5), 88.3 (C-1).
Treatment of 5 (110 mg, 210 µmol) according to the General Proce-
dure IV afforded 6 (93 mg, 73%); [a]D20+67.0 (c = 0.7, CHCl3).
1H NMR (CDCl3) d = 3.41 (dd, 1 H, H-2), 3.58 (d, 1 H, J = 9.6 Hz,
H-5), 3.87 (dd, 1 H, J5,6b = 1.3 Hz, H-6b), 3.90 (t, 1 H,
Anal. Calcd for C26H43O8Si2: C, 57.75; H, 8.20. Found C, 57.60; H,
8.20.
J
3,4 = J4,5 = 9.4 Hz, H-4), 4.13 (dd, 1 H, J5,6a = 2.0 Hz, J6a,6b = 12.7
Hz, H-6a), 4.68 (d, 1 H, J1,2 = 3.6 Hz, H-1), 5.43 (t, 1 H,
2,3 = J3,4 = 9.6 Hz, H-3).
Methyl 3-O-Benzoyl-4,6-O-(1,1,3,3-tetraisopropyl-1,3-disilox-
ane-1,3-diyl)-a-D-glucopyranoside (4b)
Treatment of 2b (437 mg, 1 mmol) according to the General Proce-
dure II afforded first 3b (336 mg, 62%). Compound 4b was eluted
next (119 mg, 22%); [a]D20 +51.5 (c = 1.0, CHCl3).
1H NMR (CDCl3): d = 1.15-0.56 (m, 28 H, TIPS), 2.14 (s, 1 H, OH),
3.44 (s, 3 H, CH3), 3.66 (d, 1 H, J5,4 = 9.5 Hz, H-5), 3.69 (dd, 1 H,
J
13C NMR (CDCl3): d = 60.7 (C-6), 67.7 (C-3), 71.7 (C-5), 73.5 (C-
4), 78.2 (C-2), 97.9 (C-1).
Anal. Calcd for C28H48O8Si2: C, 59.12; H, 8.50. Found C, 58.77; H,
8.50.
Methyl 3-O-Benzyl-4,6-O-(1,1,3,3-tetraisopropyl-1,3-disilox-
ane-1,3-diyl)-a-D-mannopyranoside (7)
J2,1 = 4.0 Hz, J2,3 = 9.7 Hz, H-2), 3.95 (dd, 1 H, J5,6b = 1.3 Hz, H-6b),
4.09 (t, 1 H, J3,4 = 9.4 Hz, H-4), 4.18 (dd, 1 H, J5,6a = 1.9 Hz,
Treatment of 2c (437 mg, 1.0 mmol) according to the General Pro-
J6a,6b = 12.6, H-6a), 4.85 (d, 1 H, J1,2 = 3.9 Hz, H-1), 5.50 (t, 1 H,
cedure III afforded 7 (481 mg, 91%); [a]D20+44.4 (c = 1.0, CHCl3).
J3,4 = 9.6 Hz, H-3).
1H NMR (CDCl3) d = 3.47 (d, 1 H, J = 9.5 Hz, H-5), 3.71 (dd, 1 H,
H-3), 3.89 (dd, 1 H, J5,6b = 1.5 Hz, H-6b), 3.93 (dd, 1 H, J2,3 = 3.2
Hz, H-2), 4.15 (dd, 1 H, J5,6a = 2.0 Hz, J6a,6b = 12.6 Hz, H-6a), 4.21
(t, 1 H, J3,4 = J4,5 = 9.4 Hz, H-4), 4.78 (d, 1 H, J1,2 = 1.2 Hz, H-1).
13C NMR (CDCl3): d = 61.4 (C-6), 66.1 (C-4), 68.9 (C-2), 73.2 (C-
5), 80.0 (C-3), 101.2 (C-1).
13C NMR (CDCl3): d = 99.6 (C-1), 76.0 (C-2), 72.2 (C-4), 71.9 (C-
5), 67.1 (C-3), 60.7(C-6).
Anal. Calcd for C26H43O8Si2: C, 57.75; H, 8.20. Found C, 57.70; H,
8.20.
Methyl 2-O-Benzoyl-4,6-O-(1,1,3,3-tetraisopropyl-1,3-disilox-
ane-1,3-diyl)-a-D-mannopyranoside (3c)
Anal. Calcd for C26H45O7Si2: C,59.28; H, 8.80. Found C, 59.00;
H,8.80.
Treatment of 2c (1.60 g, 3.7 mmol) according to the General Proce-
dure I afforded 3c (1.32 g, 67%); [a]D20 –19.5 (c = 1.2, CHCl3).
Methyl 2-O-Acetyl-3-O-benzyl-4,6-O-(1,1,3,3-tetraisopropyl-
1,3-disiloxane-1,3-diyl)-a-D-mannopyranoside (8)
1H NMR (CDCl3): d = 3.58 (d, 1 H, J = 9.4, H-5), 3.94 (dd, 1 H,
J6b,5 = 1.1 Hz, H-6b), 4.14 (dd, 1 H, J2,3 = 3.8 Hz, J3,4 = 9.5 Hz,H-3),
Treatment of 7 (150 mg, 285 µmol) according to the General Proce-
4.20 (dd, 1 H, J6a,5 = 2.0 Hz, J6a,6b = 12.7 Hz, H-6a), 4.29 (t, 1 H,
J3,4 = J4,5 = 9.4 Hz, H-4), 4.85 (d, 1 H, J1,2 = 1.2 Hz, H-1), 5.42 (dd,
1 H, J1,2 = 1.5 Hz, J2,3 = 3.5 Hz, H-2).
13C NMR (CDCl3): d = 99.3 (C-1), 72.8 (C-2), 72.7 (C-3), 70.6 (C-
4), 67.6 (C-5), 60.9 (C-6).
dure IV afforded 8 (147 mg, 90%); [a]D20+17.9 (c = 1.5, CHCl3).
1H NMR (CDCl3) d = 3.50 (d, 1 H, J = 9.2 Hz, H-5), 3.81 (dd, 1 H,
H-3), 3.88 (dd, 1 H, J5,6b = 1.2 Hz, H-6b), 4.18 (dd, 1 H, J5,6a = 1.7
Hz, J6a,6b = 12.5 Hz, H-6a), 4.29 (t, 1 H, J3,4 = J4,5 = 9.6 Hz, H-4),
4.71 (d, 1 H, H-1), 5.28 (dd, 1 H, J1,2 = 1.8 Hz, J2,3 = 3.1 Hz, H-2).
Anal. Calcd for C26H44O8Si2: C, 57.75; H, 8.20. Found C, 57.67; H,
8.18.
13C NMR (CDCl3): d = 60.9 (C-6), 65.7 (C-4), 68.9 (C-2), 73.3 (C-
5), 76.7 (C-3), 99.1 (C-1).
Methyl 3-O-Benzoyl-4,6-O-(1,1,3,3-tetraisopropyl-1,3-disilox-
ane-1,3-diyl)-a-D-mannopyranoside (4c)
Treatment of 2c (437 mg, 1.0 mmol) according to the General Pro-
cedure II afforded first 3c (370 mg, 69%). Compound 4c was eluted
next (170 mg, 31%); [a]D20 –9.9 (c = 1.2, CHCl3).
Anal. Calcd for C28H47O8Si2: C, 59.12; H, 8.50. Found C, 59.24; H,
8.38.
Methyl 3-O-Allyl-4,6-O-(1,1,3,3-tetraisopropyl-1,3-disiloxane-
1,3-diyl)-a-D-mannopyranoside (9)
Treatment of 2c (437 mg, 1.0 mmol) according to the General Pro-
cedure III afforded 9 (399 mg, 84%); mp 113°C; [a]D20+34.5
(c = 1.1, CHCl3).
1H NMR (CDCl3): d = 3.42–3.37 (m, 1 H, H-5), 3.53 (dd, 1 H,
J3,4 = 9.3, H-3), 3.82 (dd, 1 H, J5,6b = 1.5, J6a,6b = 12.5 Hz, H-6b),
1H NMR (CDCl3): d = 3.67 (d, 1 H, J = 9.4 Hz, H-5), 3.95 (dd, 1 H,
J5,6b = 1.4 Hz, H-6b), 4.09 (dd, 1 H, H-2), 4.20 (dd, 1 H, J5,6a = 2.1
Hz, J6a,6b = 12.5 Hz, H-6a), 4.50 (t, 1 H, J3,4 = J4,5 = 9.7 Hz, H-4),
4.78 (d, 1 H, J1,2 = 1.7 Hz, H-1), 5.48 (dd, 1 H, J3,2 = 3.2 Hz,
J3,4 = 9.9 Hz, H-3).
Synthesis 1999, No. 9, 1661–1665 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Regioselective Alkylation and Acylation of Siloxane Protected Glycopyranosides
1665
3.92 (dd, 1 H, J2,3 = 3.4, H-2), 4.11–4.04 (m, 4 H, H-4, H6a, Allyl-
CH2), 4.73 (d, 1 H, J1,2 = 1.2 Hz, H-1), 5.11 (ddd, 1 H, H3´b), 5.21
(ddd, 1 H, J3´a,3´b = 3.0, J3´a,1´a,b = 1.4, H-3´a), 5.94 (ddt, 1 H,
J2´,3´a = 17.2 Hz, J2´,3´b = 10.3 Hz, J2´, 1´a,b = 5.7 Hz, H-2´).
13C NMR (CDCl3): d = 61.1 (C-6), 66.6 (C-4), 69.6 (C-6´), 70.0 (C-
5´), 74,4 (C-5), 75.6 (C-2´), 75.9 (C-4´), 77.4 (C-2), 79.1 (C-
2´),79.7 (C-3), 85.3 (C-1,
JC1´,H1´ = 169.45 Hz).
JC1,H1 = 166.41 Hz), 99.6 (C-1´,
13C NMR (CDCl3): d = 60.96 (C-6), 65.5 (C-4), 68.5 (C-2), 72.7 (C-
5), 78.9 (C-3), 100.8 (C-1).
Anal. Calcd for C67H94O11SSi2: C, 69.15; H, 8.14. Found C, 69.01,
H, 8.19.
Anal. Calcd for C22H44O7Si2: C, 55.43; H, 9.30. Found C, 55.28, H,
9.23.
Acknowledgement
Methyl 2-O-Acetyl-3-O-allyl-4,6-O-(1,1,3,3-tetraisopropyl-1,3-
disiloxane-1,3-diyl)-a-D-mannopyranoside (10)
We thank the Deutsche Forschungsgemeinschaft and the Fonds der
Chemischen Industrie for the financial support of this work. We are
also grateful to Dr. Schmickler, University of Cologne for recording
the NMR spectra.
Treatment of 9 (150 mg, 315 µmol) according to the General Proce-
dure IV afforded 10 (149 mg, 91%); [a]D20+17.0 (c = 1.2, CHCl3).
1H NMR (CDCl3) d = 3.50 (d, 1 H, J = 9.6 Hz, H-5), 3.88 (dd, 1 H,
J5,6b = 1.3 Hz, H-6b), 3.71 (dd, 1 H, H-3), 4.17 (dd, 1 H, J5,6a = 1.9
Hz, J6a,6b = 12.5 Hz, H-6a), 4.07–4.02 (m, 2H Allyl-CH2), 4.21 (t, 1
H, J3,4 = J4,5 = 9.6 Hz, H-4), 4.70 (d, 1 H, H-1), 5.13 (ddd, 1 H,
H3´b), 5.24 (ddd, 1 H, J3´a,3´b = 3.5, J3´a,1´a,b = 1.4, H-3´a), 5.25 (dd,
1 H, J1,2 = 1.8 Hz, J2,3 = 3.3 Hz, H-2), 5.86 (ddt, 1 H, J2´,3´a = 17.2
Hz, J2´,3´b = 10.4 Hz, J2´, 1´a,b = 5.6 Hz, H-2´).
13C NMR (CDCl3): d = 60.9 (C-6), 65.5 (C-4), 69.0 (C-2), 73.2 (C-
5), 76.3 (C-3), 99.1 (C-1).
References
(1) Markiewicz, W. T. J. Chem. Res. (S) 1979, 24.
(2) Ziegler, T.; Dettmann, R.; Bien, F.; Jurisch, C. Trends in Org.
Chem. 1997, 6, 91.
(3) Verdegaal, C. H. M.; Jansse, P. L.; de Rooij, J. F. M.; van
Boom, J. H. Tetrahedron Lett. 1980, 21, 1571.
(4) van Boeckel, C. A. A.; van Boom, J. H. Tetrahedron Lett.
1980, 21, 3705.
(5) Oltvoort, J. J.; Klosterman, M.; van Boom, J. H. Trav. Chim.
Pays-Bas 1983, 102, 501.
(6) Thiem, J.; Duckstein, V.; Prahst, A.; Matzke, M. Liebigs Ann.
Chem. 1987, 289.
Anal. Calcd for C24H46O8Si2: C, 55.56; H, 8.94. Found C, 55.39; H,
8.92.
Octyl 3-O-Benzyl-4,6-O-(1,1,3,3-tetraisopropyl-1,3-disiloxane-
1,3-diyl)-1-thio-a-D-mannopyranoside (11)
Reaction of a solution of 2d (2.46 g, 4.5 mmol) in benzene (280 mL)
with Bu2SnO (1.22g, 4.9 mmol), benzyl bromide (2.14 mL, 9
mmol), Bu4NI (3.33 g, 9 mmol) and 4 Å molecular sieves (5 g) ac-
cording to the General Procedure III afforded 11 (1.86 g, 65%);
[a]D20 +79.5 (c = 1.0, CHCl3).
1H NMR (CDCl3): d = 3.69 (dd, 1 H, J2,3 = 3.2 Hz, H-3), 3.89–3.81
(m, 2 H, H-5,6b), 3.98 (d, 1 H, J = 2.4 Hz, H-2), 4.16 (dd, 1 H,
J5,6a = 1.9 Hz, J6a,6b = 12.4 Hz, H-6a), 4.25 (t, 1 H, J3,4 = J4,5 = 9.3
Hz, H-4), 5.36 (s, 1 H, H-1).
(7) Ziegler, T. Topics Curr. Chem. 1997, 186, 203.
Ziegler, T.; Neumann, K.; Eckhardt, E.; Herold, G.;
Pantkowski, G. Synlett 1991, 699.
Heuer, M.; Hohgardt, K.; Heinemann, F.; Kuhne, H.;
Diertrich, W.; Grzelak, D.; Müller, D.; Welzel, P.; Markus,
A.; van Heijenoort, Y.; van Heijenoort, J. Tetrahedron 1994,
50, 2029.
(8) Tsuda, Y.; Haque, M. E.; Yoshimoto, K. Chem. Pharm Bull.
1983, 31, 1612.
13C NMR (CDCl3): d = 61.1 (C-6), 65.9 (C-4), 70.1 (C-2), 73.5 (C-
David, S.; Hanessian, S. Tetrahedron 1985, 41, 643.
(9) Grindley, T. B. In Synthetic Oligosaccharides; Kovac, P., Ed.;
ACS Symposium Series 560, American Chemical Society:
Washigton DC, 1994, p 51.
5), 79.9 (C-3), 84.2 (C-1).
Anal. Calcd for C33H60O6SSi2: C, 61.81; H, 9.43; S, 5.00. Found C,
61.86; H, 9.41; S, 5.05.
David, S. In Preparative Carbohydrate Chemistry; Hanessian,
S., Ed.; Marcel Dekker: New York, 1997, p 69.
Ziegler, T. In Carbohydrate Chemistry; Boons, G.-J., Ed.;
Blackie Academic: London, 1998, p 21.
Octyl 3-O-Benzyl-2-O-(2,3,4,6-tetra-O-benzyl-a-D-galactopyra-
nosyl)-4,6-O-(1,1,3,3-tetraisopropyl-1,3-disiloxane-1,3-diyl)-1-
thio-a-D-mannopyranoside (13)
(10) Ichikawa, Y.; Monden, R.; Kunzuhara, H. Tetrahedron Lett.
1986, 27, 611.
(11) Ziegler, T.; Seidl, U. J. Carbohydr. Chem. 1991, 10, 813.
(12) Ziegler, T.; Eckhardt, E.; Neumann, K.; Birault, V. Synthesis
1992, 1013.
(13) Ziegler, T.; Dettmann, R.; Duszenko, M.; Kolb, V.
Carbohydr. Res. 1996, 295, 7.
(14) El-Kattan, Y.; Gosselin, G.; Imbach, J.-L. J. Chem. Soc.
Perkin Trans. 1 1994, 10, 1289.
(15) Srivastava, S.C.; Roy, S.K. US Patent 5 214 135, 1993; Chem.
Abstr. 1993, 119, 2 503 87.
(16) Käsbeck, L.; Kessler, H. Liebigs Ann./Recueil 1997, 169.
(17) Kohata, K.; Konno, T.; Meguro, H. Tetrahedron Lett. 1980,
21, 3771.
A solution of 11 (254 mg, 0.4 mmol) and 1215 (245 mg, 0.4 mmol)
in anhyd Et2O (10 mL) was stirred for 1 h with 4 Å molecular sieves
at r.t. under argon. After 0.5 h, 2,4-di-tert-butyl pyridine (220 µL,
1.0 mmol) was added and the solution was stirred for 1 h. Then, me-
thyl triflate (110 µL, 1.0 mmol) was added and the mixture was al-
lowed to react for 1.5 h. An additional amount of 12 (122 mg, 0.2
mmol) was then added and stirring was continued for 1.5 h. The
mixture was quenched with Et3N (1 mL) and diluted with CH2Cl2.
After filtration through a layer of Celite the solution was washed
with 1 M aq HCl, neutralized with aq satd NaHCO3 solution, dried
(Na2SO4), filtered and concentrated. Chromatography of the residue
(hexane/EtOAc, 20:1 to 10:1) afforded 13 (228 mg, 49%) as a col-
20
orless oil; [a]D +48 (c = 1.3, CHCl3).
1H NMR (CDCl3): d = 3.44 (dd, 1 H, J5´,6´b = 5.6 Hz, H-6´b), 3.51
(dd, 1 H, J5´,6´a = 6.7 Hz, J6´a,6´b = 10.0 Hz, H-6´a), 3.70 (dd, 1 H,
J2,3 = 2.2 Hz, J3,4 = 9.6 Hz, H-3), 3.87–3.81 (m, 2 H, H-5, H-6b),
3.99 (s, 2 H, H-2´, H-4´), 3.91 (s, 1 H, H-3´),4.04 (d, 1 H, J = 1.3
Hz, H-2), 4.21–4.17 (m, 2 H, H-6a, H-5´),4.46 (t, 1 H,
Sarkar, A.K.; Matta, K.L. Carbohydr. Res. 1992, 233, 245.
Article Identifier:
1437-210X,E;1999,0,09,1661,1665,ftx,en;H02499SS.pdf
J3,4 = J4,5 = 9.7 Hz, H-4), 5.16 (s, 1 H, H-1´), 5.45 (s, 1 H, H-1).
Synthesis 1999, No. 9, 1661–1665 ISSN 0039-7881 © Thieme Stuttgart · New York