DDQ-mediated oxidation of 4,6-O-methoxybenzylidene-protected saccharides in the presence of various nucleophiles: Formation of 4-OH, 6-Cl, and 6-Br derivatives

Article abstract of DOI:10.1021/jo952177v

Treatment of 4,6-O-p-methoxybenzylidene-protected pyranosidic mono- and disaccharides with 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ), in the presence of a few equivalents of water, gave the corresponding 6- and 4-O-p-methoxybenzoates with unprotected hydroxyl groups in the 4- and 6-position in the ratio ~4:1 and in 85-98% yield. Dry conditions in the presence of halide salts gave the 6-deoxychloro and -bromo 4-O-p-methoxybenzoates exclusively, in >90% yield.

Full text of DOI:10.1021/jo952177v

2394
J . Org. Chem. 1996, 61, 2394-2400
DDQ-Med ia ted Oxid a tion of 4,6-O-Meth oxyben zylid en e-P r otected
Sa cch a r id es in th e P r esen ce of Va r iou s Nu cleop h iles: F or m a tion
of 4-OH, 6-Cl, a n d 6-Br Der iva tives
Zhiyuan Zhang and Go¨ran Magnusson*
Organic Chemistry 2, Chemical Center, The Lund Institute of Technology, University of Lund,
P.O. Box 124, S-221 00 Lund, Sweden
Received December 7, 1995X
Treatment of 4,6-O-p-methoxybenzylidene-protected pyranosidic mono- and disaccharides with 2,3-
dichloro-5,6-dicyano-p-benzoquinone (DDQ), in the presence of a few equivalents of water, gave
the corresponding 6- and 4-O-p-methoxybenzoates with unprotected hydroxyl groups in the 4- and
6-position in the ratio ∼4:1 and in 85-98% yield. Dry conditions in the presence of halide salts
gave the 6-deoxychloro and -bromo 4-O-p-methoxybenzoates exclusively, in >90% yield.
In tr od u ction
In contrast to the reductive cleavage reactions that give
benzyl ethers, oxidative cleavage gives benzoyl esters.
The latter are labile under alkaline conditions and can
therefore be simply and selectively removed in later
stages of a synthetic route. In order to enhance the ease
of oxidation, p-methoxybenzylidene acetals were chosen
as protecting groups. With non-saccharidic acetals, a
number of oxidants have thus been evaluated, including
ozone,8 pyridinium dichromate/t-BuOOH,9 NaBO3‚4H2O/
Ac2O,10 and t-BuOOH/Pd(OCOCF3)(t-BuOOH).11 How-
ever, the regioselectivity obtained with most of these
reagents was rather poor. Treatment of some p-meth-
oxybenzylidene acetals of furanoses with 2,3-dichloro-5,6-
dicyanobenzoquinone (DDQ) gave the two expected re-
gioisomeric p-methoxybenzoyl esters in the ratio 7:3.12
Oxidative cleavage of 4,6-O-benzylidene acetals of py-
ranosides, using Pd(OAc)2 or CuCl2/t-BuOOH, gave the
benzoyl esters in high yield, but low regioselectivity.13
To the best of our knowledge, oxidative cleavage of 4,6-
O-p-methoxybenzylidene acetals of pyranosidic sugars
has not been reported. We now disclose our results from
an investigation of DDQ-promoted cleavage of such
acetals. Using different reaction conditions (Tables 1 and
2), the 4-hydroxy, 6-deoxychloro, and 6-deoxybromo
derivatives, carrying a p-methoxybenzoyl group (MBz) in
the 6- or 4-position, respectively, were formed as the main
products.
Cyclic acetals are versatile protecting groups for diols
and have found widespread use in carbohydrate synthe-
sis.1 Well-known examples include 3,4-O-isopropylidene
and 4,6-O-benzylidene protection in hexopyranosides and
1,2;5,6-di-O-isopropylidene-protection in hexofuranosides.
In addition to protection/deprotection, regioselective cleav-
age of benzylidene acetals by both reductive and oxidative
procedures gives access to partly protected sugars with
only one unprotected hydroxyl group, suitable as e.g.
glycosyl acceptors.
Hanessian,2 and Hullar and Siskin,3 independently
found in 1966 that 4,6-O-benzylidene acetals could be
transformed into the corresponding 4-O-benzoyl-6-deoxy-
bromo derivatives, by treatment with N-bromosuccinim-
ide (NBS) in tetrachloromethane. This procedure has
developed into one of the standard reactions for regiose-
lective functionalization of carbohydrates. Following
these initial examples, further search for effective meth-
ods for regioselective ring-opening of sugar acetals has
yielded other valuable procedures for the preparation of
partially protected sugars.4
Reductive cleavage of sugar benzylidene acetals, using
reagents such as LiAlH4/AlCl3,5 NaCNBH3/HCl,6 and
i-Bu2AlH,7 gives benzyl ether sugars with one unpro-
tected hydroxyl group. The regioselectivity varies be-
tween these methods. Generally speaking, LiAlH4/AlCl3
and NaCNBH3/HCl give products with unprotected 6-OH
and 4-OH, respectively. The latter reagent is now
generally accepted for reliable regioselective preparation
of pyranosidic glycosyl acceptors.
Resu lts a n d Discu ssion
The acetals 2-10, depicted in Chart 1, were used as
starting materials in the DDQ-mediated cleavage reac-
tions discussed below. Treatment of 2-(trimethylsilyl)-
ethyl â-D-galactopyranoside14 with p-methoxybenzalde-
hyde dimethyl acetal and p-toluenesulfonic acid gave 1
(98%). Benzoylation and benzylation of 1 gave 2 (95%)
and 3 (90%), respectively. Acetals 4-10 were prepared
according to published procedures.14-17
X Abstract published in Advance ACS Abstracts, March 15, 1996.
(1) Greene, T. W.; Wuts P. G. M. Protecting groups in organic
synthesis, 2nd ed.; Wiley-Interscience: New York, 1990.
(2) (a) Hanessian, S. Carbohydr. Res. 1966, 2, 86-88. (b) Hanessian,
S.; Plessas, N. R. J . Org. Chem. 1969, 34, 1035-1044, 1045-1052,
1053-1058.
(3) Failla, D. L.; Hullar, T. L.; Siskin, S. B. J . Chem. Soc., Chem.
Commun. 1966, 716-717.
(4) (a) J acobsen, S.; Pedersen, C. Acta Chem. Scand. B 28 1974,
866-872. (b) Binkley, R. B.; Goewey, G. S.; J ohnston, J . C. J . Org.
Chem. 1984, 49, 992-996.
(8) Deslongchamps, P.; Atlani, P.; Fre´hel, D.; Malaval, A.; Moreau,
C. Can. J . Chem. 1974, 52, 3651-3664.
(9) Chidambaram, N.; Bhat, S.; Chandrasekaran, S. J . Org. Chem.
1992, 57, 5013-5015.
(5) (a) Bhattacharjee, S. S.; Gorin, P. A. J . Can. J . Chem. 1969, 47,
1195-1206. (b) Lipta´k, A.; J oda´l, I.; Na´na´si, P. Carbohydr. Res. 1975,
44, 1-11.
(10) Bhat, S.; Ramesha, A. R.; Chandrasekaran, S. Synlett 1995,
57, 329-330.
(6) (a) Horne, D. A.; J ordan, A. Tetrahedron Lett. 1978, 1357-1358.
(b) Garegg, P. J .; Hultberg, H. Carbohydr. Res. 1981, 93, C10-C11.
(c) Garegg, P. J .; Hultberg, H.; Wallin, S. Carbohydr. Res. 1982, 108,
97-101.
(11) Hosokawa, T.; Imada, Y.; Murahashi, S. J . Chem. Soc., Chem.
Commun. 1983, 1245-1246.
(12) Oikawa, Y.; Yoshioka, T.; Yonemitsu, O. Tetrahedron Lett. 1982,
23, 889-892.
(7) Mikami, T.; Asano, H.; Mitsunobu, O. Chem. Lett. 1987, 2033-
2036.
(13) Sato, K.; Igarashi, T.; Yanagisawa, Y.; Kawauchi, N.; Hash-
imoto, H.; Yoshimura, J . Chem. Lett. 1988, 1699-1702.
0022-3263/96/1961-2394$12.00/0 © 1996 American Chemical Society

Oxidation of 4,6-O-Methoxybenzylidene-Protected Saccharides
J . Org. Chem., Vol. 61, No. 7, 1996 2395
Ch a r t 1
Ch a r t 2
Syn t h esis of 4-O- a n d 6-O-p -Met h oxyb en zoyl-
P r otected Sa cch a r id es (Ch a r t 2). An initial attempt,
based on a published procedure,12 to regioselectively
cleave the acetal ring of 2 with DDQ in dichloromethane/
water (17:1) resulted in hydrolysis of the acetal to give
the corresponding 4,6-diol 13. Similar DDQ-induced
hydrolysis of other acetals has been reported recently.18
It seems as if excess water in the reaction mixture leads
to hydrolysis rather than the desired oxidative cleavage
to MBz-esters. When the reaction was run with 2 in
acetonitrile or dioxane (without previous drying of the
solvent; supposed to contain excess water) only diol 13
was formed. Using essentially the published conditions18
[DDQ (0.2 equiv), MeCN/H2O, 9:1, 2-6 h, 45 °C], com-
pounds 2 and 517 were hydrolyzed to give the correspond-
ing diols 13 and 16 in 97 and 95% isolated yield,
respectively.
When the solvent (toluene or 1,2-dichloroethane) was
predried and a controlled amount of water was added
(preabsorbed in molecular sieves), only the desired 4-O-
and 6-O-MBz-esters 11 and 12 were obtained from 2
(Chart 2 and Table 1). Addition of a small amount of
acetic acid increased the 11/12 ratio.
(14) J ansson, K.; Ahlfors, S.; Frejd, T.; Kihlberg, J .; Magnusson, G.;
Dahme´n, J .; Noori, G.; Stenvall, K. J . Org. Chem. 1988, 53, 5629-
5647.
(15) Zhiyuan, Z.; Magnusson, G. Carbohydr. Res. 1994, 262, 79-
101.
(16) Zhang, Z.; Magnusson, G. J . Org. Chem. 1995, 60, 7304-7315.
(17) Zhang, Z.; Magnusson, G. J . Org. Chem. 1996, 61, 2383.
(18) (a) Ferna´ndez, J . M. G.; Mellet, C. O.; Mar´ın, A. M.; Fuentes,
J . Carbohydr. Res. 1995, 274, 263-268. (b) Tanemura, K.; Suzuki, T.;
Horaguchi, T. J . Chem. Soc., Chem. Commun. 1992, 979-980.
In addition to compound 2 we tested the 4,6-O-p-
methoxybenzylidene acetals 5-10. The glucoside 5 was
more sensitive than 2 toward hydrolysis. Thus, when
water was added to the reaction mixture containing 5
(same conditions as method A in Table 1), a substantial
amount of diol 16 was formed. However, by omitting the
addition of water and lowering the amount of acetic acid

2396 J . Org. Chem., Vol. 61, No. 7, 1996
Zhang and Magnusson
Ch a r t 3
Ta ble 1. Syn th esis of 4-O- a n d
to 1.5 equiv (method B), 14 and 15 were isolated in 76
and 13% yield, respectively, and no diol 16 was formed.
Presumably, the nondried solvent and nonactivated
molecular sieves contained enough water for the reaction
to proceed to completion.
6-O-p-Meth oxyben zoyl-P r otected Sa cch a r id es by
DDQ-Med ia ted Oxid a tive Clea va ge of
4,6-O-p-Meth oxyben zylid en e Aceta ls
starting mtrla
methodb
productc
yieldd (%)
2
5
6
7
8
A
B
C
D
A
A
E
11/12
14/15
17/18/diol
19/20
21/22
79/19
76/13
66/19/3
85/6e
79/20
83/16
65/31
92f
The 2- and 3-deoxyglucosides17 6 and 7 were, as
expected, more sensitive toward hydrolysis than 5.
Decreasing the amount of acetic acid to 0.2 equiv (method
C) gave with 6 the desired 17 (66%) and 18 (19%),
together with a small amount of diol (3%). The 3-deoxy-
glucoside 7 was even more acid sensitive, decomposing
in the presence of silica gel. Omitting the addition of
acetic acid (method D) permitted the transformation of
7 into a mixture of 19 and 20. However, the regioselec-
tivity was low in the absence of acid (19/20 3:2). We have
previously shown that p-methoxybenzoyl groups migrate
from the 4- to the 6-position by treatment with silver
nitrate/potassium fluoride.17,19 Under these conditions,
the 19/20 ratio was shifted from 3:2 to 14:1 and pure 19
was obtained in 85% yield.
9
23/24
25/26
10
2 + 4
A
11/12 + 4
a
b
See Chart 1. A: DDQ (1.5 equiv), AcOH (5 equiv), H2O (2
equiv), nonactivated molecular sieves (4 Å), toluene, 80 °C; B:
DDQ (1.5 equiv), AcOH (1.5 equiv), nonactivated molecular sieves
(4 Å), toluene, 80 °C; C: DDQ (2 equiv), AcOH (0.2 equiv),
nonactivated molecular sieves (4 Å), toluene, 80 °C (ref 17); D:
DDQ (2 equiv), nonactivated molecular sieves (4 Å), toluene, 80
°C (ref 17); E: DDQ (1.5 equiv), NaHSO4 (4.5 equiv), H2O (5 equiv),
18-crown-6 (cat.), nonactivated molecular sieves (4 Å), toluene, 70
d
°C (ref 16). c See Chart 2. Isolated yields of the 4OH-6OMBz/
4OMBz-6OH products. e After rearrangement and chromatography
The lactoside15 8 was treated under the same condi-
tions as galactoside 2 (method A) to give 21 and 22 in 79
and 20% yield, respectively. These conditions worked
equally well with the 6-deoxylactoside17 9, giving 23 and
24 in 83 and 16% yield, respectively. The 3′-deoxylac-
toside16 10 was transformed into 25 and 26 in 65 and
31% yield, respectively, in the presence of added water
and sodium hydrogen sulfate (method E), indicating once
more that galactosides are less prone to hydrolysis than
glucosides (cf. 10 and 7).
of the original mixture (ref 17). f Yield of unreacted 4.
4 and 6. In an initial attempt along these lines, com-
pound 2 was treated with DDQ (2 equiv), potassium
chloride (3 equiv), and 18-crown-6 (0.5 equiv) in dry 1,2-
dichloroethane. The 6-deoxychloro galactoside 27 was
formed together with a small amount of compound 11;
compound 27 was isolated in 85% yield. The same result
was obtained when toluene was used as solvent (method
F, Table 2).
Treatment of the 2,3-O-benzylated galactoside 3 under
the conditions of method E gave a complex mixture of
debenzylated products, indicating that electron-with-
drawing protecting groups (such as benzoyl groups)
stabilize the compounds much better than benzyl pro-
tecting groups.
To our surprise, attempted formation of the corre-
sponding deoxyfluoro galactoside from 2 in the presence
of potassium fluoride instead of potassium chloride, also
gave the deoxychloro galactoside 27. In order to inves-
tigate the nature of the chloride-ion source, the 1,2-
dichloroethane solvent was substituted by toluene, but
27 was also here the main product formed. The same
results were obtained when potassium bromide, potas-
sium azide, and lithium tosylate were used as the
potential nucleophiles. In an experiment where 2 was
treated with 1.3 equiv of DDQ and only 0.3 equiv of
potassium chloride, the 6-deoxychloro compound 27 was
isolated in 72% yield. The logical conclusion is that DDQ,
or its reaction products, reacts with nucleophiles present
in solution (including water) thus liberating chloride ions,
which can then react with the activated p-methoxyben-
zylidene acetal (Scheme 1). Substitution of chloride ion
by fluoride ion was reported to occur when 2,3,5,6-
tetrachloro-p-benzoquinone was treated with potassium
fluoride.20 Consequently, a halogen source different from
Finally, the 4,6-O-benzylidene acetal14 4 was virtually
stable under the conditions that converted 2 into 11 and
12. Thus, when a mixture of compounds 2 and 4 was
treated according to method A, compound 2 was con-
sumed but 4 remained unchanged and 92% of 4 was
recovered from the reaction mixture.
Syn th esis of 4-O-p-Meth oxyben zoyl-6-d eoxych lo-
r o a n d -br om o Sa cch a r id es (Ch a r t 3). As depicted
in Scheme 1, a benzyloxonium ion is considered to be an
early intermediate in DDQ-oxidation of 4,6-O-p-meth-
oxybenzylidene acetals. Such intermediates should in
principle be amenable to nucleophilic attack at position
(19) Yasumori, T.; Sato, K.; Hashimoto, H.; Yoshimura, J . Bull.
Chem. Soc. J pn. 1984, 57, 2538-2542.

Oxidation of 4,6-O-Methoxybenzylidene-Protected Saccharides
Sch em e 1
J . Org. Chem., Vol. 61, No. 7, 1996 2397
Ta ble 2. Syn th esis of 6-Deoxych lor o- a n d
6-Deoxybr om o-4-O-p-m eth oxyben zoyl-P r otected
Sa cch a r id es by DDQ-Med ia ted Oxid a tive Clea va ge of
4,6-O-p-Meth oxyben zylid en e Aceta ls in th e P r esen ce of
Ha lid e Don or s
desired deoxyhalo sugars. We assume that a Lewis acid
is needed in addition to the halide source, in order to
expedite the nucleophilic attack on the activated 4,6-O-
p-methoxybenzylidene acetal. Copper(II) halides were
found to function well as Lewis acids in these reactions.
Thus, the combination DDQ/CuCl2/Bu4NCl (1:1:2; method
H) gave with 2, 5, and 8 the desired 6-deoxychloro
derivatives 27, 29, and 34 in 96, 91, and 97% isolated
yield. Using the same starting materials with DDQ/
CuBr2/Bu4NBr (1:1:2, method J ) gave 28, 30, and 35 in
93, 88, and 93% yield. Compound 35 was treated with
tributyltin hydride to give the corresponding 6′-deoxy-
lactoside 36, clearly demonstrating that the bromine
atom was present in the 6′-position of 35.
In analogy with the experiment described in Table 1
(2 + 4) the stability of the 4,6-O-benzylidene derivative
4 was investigated with the DDQ/CuBr2/Bu4NBr reagent.
After 2 days under the conditions of method J , ap-
proximately 90% of 4 was recovered intact, showing that
combined p-methoxybenzylidene and benzylidene protec-
tion of pyranosides can be used to advantage when
selective deprotection or halogenation is desired with
larger oligosaccharides that contain both protecting
groups.
starting mtrla
methodb
productc
yieldd (%)
2
2
2
2
2
5
5
5
5
3
8
8
8
8
F
G
H
I
27 (Cl)
27 (Cl)
27 (Cl)
28 (Br)
28 (Br)
29 (Cl)
29 (Cl)
30/31 (Br)
30 (Br)
32/33 (Br)
34 (Cl)
35 (Br)
35 (Br)
35 (Br)
85
88
96
90
93
71
91
75/20
88
33/53
97
83
93
95
J
G
H
I
J
K
H
I
J
L
a
b
See Chart 1. F: DDQ, KCl, 18-crown-6 (cat.), molecular
sieves (4 Å), toluene, 80 °C; G: DDQ, TMS-Cl, molecular sieves
(4 Å), 1,2-dichloroethane 50 °C; H: DDQ, CuCl2/Bu4NCl, molecular
sieves (4 Å), 1,2-dichloroethane, reflux; I: DDQ, TMS-Br, molec-
ular sieves (4 Å), 1,2-dichloroethane, 50 °C; J : DDQ, CuBr2/
Bu4NBr, molecular sieves (4 Å), 1,2-dichloroethane, reflux; K:
DDQ, TMS-Br, molecular sieves (4 Å), chloroform, 50 °C; L: NBS,
d
CCl4, reflux. c See Chart 3. Isolated yields.
Mech a n ist ic Con sid er a t ion s. Oxidation of allylic
alcohols by DDQ was suggested to occur via an ionic
rather than a radical mechanism.21 It seems reasonable
to assume that the DDQ-oxidations of p-methoxyben-
zylidene acetals reported here also proceed via ionic
intermediates, as depicted in Scheme 1. Attack by
nucleophiles (H2O, Cl-, or Br-) on the initially formed
p-methoxybenzyloxonium ion can in principle take place
at three different positions. The benzylic position, car-
rying the highest positive charge density, probably
undergoes the most rapid nucleophilic attack (a, Scheme
1). Reaction with water gives a hemi-orthoester inter-
mediate, which can react further by cleavage of the
dioxine ring to form the desired p-methoxybenzoyl ester
with unprotected HO-4 (d) or HO-6 (e), as shown in Table
1. Alternatively, the HO-6 compound may be formed via
direct attack by water at C-6 (b). Yet another possibility
includes migration of the p-methoxybenzoyl group from
the 4- to the 6-position after initial formation of the HO-6
compound, although this is considered to be less likely.
In contrast to the water case above, attack at the
benzylic carbenium ion by Cl- or Br- is nonproductive
and the carbenium ion is recreated due to the good
leaving group characteristics of the halogenide ions.
Attack at C-6 leads on the other hand to the desired
potassium halide had to be found when halosugars other
than chlorides are desired.
Treatment of 2 and 5 with DDQ and trimethylsilyl
chloride in 1,2-dichloromethane (method G) gave 27 and
29 in 88 and 71% yield, respectively. Similarily, when
trimethylsilyl bromide was used with 2 and 8 (method
I), the deoxybromo galacto- and lactosides 28 and 35 were
obtained in 90 and 83% yield, respectively. However,
with glucoside 5, the yield of the desired deoxybromo
glucoside 30 was only 75% and the deoxybromo furano-
side 31 was formed as a byproduct (20%). Another
disadvantage with trimethylsilyl bromide was found on
attempted bromination of the 2,3-di-O-benzyl galactoside
3 (method K). Both the desired bromodeoxy compound
32 (33%) and the partially debenzylated derivative 33
(53%) were obtained. Finally, attempted conversion of
2 using DDQ and trimethylsilyl iodide gave a very
complex reaction mixture. It was concluded that tri-
methylsilyl chloride and bromide are acceptable reagents
when stable starting materials, such as 2 and 8, are used.
However, with less stable compounds, such as 3 and 5, a
less aggressive reagent is desired.
Preliminary experiments with 2 and DDQ/tetrabutyl-
ammonium chloride and bromide did not produce the
(21) Burstein, S. H.; Ringold, H. J . J . Am. Chem. Soc. 1964, 86,
4952-4958.
(20) Wallenfels, K.; Draber, W. Chem. Ber. 1957, 2819-2832.

2398 J . Org. Chem., Vol. 61, No. 7, 1996
Zhang and Magnusson
3.30 (bs, 1 H), 1.05 (m, 2 H), 0.03 (s, 9 H); HRMS calcd for
C33H42O7SiNa (M + Na) 601.2598, found 601.2583.
6-deoxyhalo products, as shown in Table 2. It is note-
worthy that no 4-deoxyhalo compounds were found in the
reaction mixtures, which means that route c (Scheme 1)
is strongly disfavored compared to route b. This is in
agreement with Hanessian’s results with NBS-mediated
tranformation of 4,6-O-benzylidene acetals into the cor-
responding 4-O-benzoyl-6-deoxybromo compounds.2b
2-(Tr im eth ylsilyl)eth yl 2,3-Di-O-ben zoyl-4,6-O-p-m eth -
oxyben zylid en e-â-D-glu cop yr a n osid e17 (5). 2-(Trimethyl-
silyl)ethyl 4,6-O-p-methoxybenzylidene-â-D-glucopyranoside17
(1.93 g, 4.9 mmol) was benzoylated as described in the
preparation of 2. The crude product was chromatographed
(SiO2, heptane/EtOAc 5:1 f 2:1) to give 5 (2.67 g, 91%). The
physical data for 5 were as described.17
2-(Tr im eth ylsilyl)eth yl 2,3-Di-O-ben zoyl-6-O-p-m eth -
oxyben zoyl-â-D-ga la ctop yr a n osid e (11) a n d 2-(Tr im eth -
ylsilyl)eth yl 2,3-Di-O-ben zoyl-4-O-p-m eth oxyben zoyl-â-
D-ga la ctop yr a n osid e (12). Meth od A: H2O (5.9 µL, 0.3
mmol) and AcOH (28.3 µL, 0.8 mmol) were absorbed in crushed
(nonactivated) molecular sieves (100 mg). The sieves were
added to a solution of compound 2 (100 mg, 0.17 mmol) in
toluene (5 mL). The mixture was stirred for 5 min, DDQ (58
mg, 0.25 mmol) was added, and the temperature was raised
to 80 °C. After 20 h, TLC (toluene/EtOAc 4:1) showed that 2
had been consumed. The mixture was diluted with EtOAc (50
mL), filtered through Celite, washed with saturated aqueous
NaHCO3 (2 × 25 mL) and water (25 mL), dried (Na2SO4),
filtered, and concentrated. The residue was chromatographed
(SiO2, heptane/EtOAc 3:1 f 2:1) to give 11 (80.5 mg, 79%) and
Exp er im en ta l Section
Gen er a l Meth od s. NMR spectra were recorded in CDCl3;
chemical shifts are relative to Me4Si. TLC was performed on
Kieselgel 60 F254 (Merck). Products were chromatographed on
Kieselgel 60 (Merck, 35-70 mesh). Melting points are uncor-
rected. Solvents were freshly distilled over drying agents
under N2 (toluene/Na, 1,2-dichloroethane/CaH2, chloroform/
CaH2). Powdered molecular sieves were activated at 180 °C
and then with a flame under vacuum for 5 min and kept under
vacuum for 1 h before use. Tetrabutylammonium halides and
cupric halides were treated in the same way. Compounds 4
and 6-10 have been described.14-17
2-(Tr im eth ylsilyl)eth yl 4,6-O-p-Meth oxyben zylid en e-
â-D-ga la ctop yr a n osid e (1). To a mixture of 2-(trimethylsi-
lyl)ethyl â-D-galactopyranoside14 (8.00 g, 28.6 mmol), p-meth-
oxybenzaldehyde dimethyl acetal (8.60 mL, 57.3 mmol), and
dry acetonitrile (170 mL) was added toluenesulfonic acid
monohydrate (320 mg) at room temperature. After 1 h, the
mixture was neutralized with triethylamine (1.0 mL) and
concentrated. The residue was chromatographed (SiO2, EtOAc/
heptane 3:1 f 4:1) to give 1 (11.14 g, 98%); Recrystallization
12 (19.1 mg, 19%). Compound 11 had mp 113-115 °C; [R]22
D
1
+39.7° (c 1.0, CHCl3); H-NMR δ 5.75 (dd, 1 H, J ) 10.3, 7.9
Hz), 5.34 (dd, 1 H, J ) 10.3, 3.2 Hz), 4.74 (d, 1 H, J ) 7.9 Hz),
4.68, 4.58 (dd, 1 H each, J ) 11.4, 6.7, 6.5 Hz), 4.34 (d, 1 H, J
) 2.7 Hz), 3.86 (s, 3 H), -0.08 (s, 9 H). Anal. Calcd for
C33H38O10Si: C, 63.6; H, 6.2. Found: C, 63.7; H, 6.2. Com-
pound 12 had mp 162-163 °C; [R]22 +221.5° (c 1.0, CHCl3);
D
1H-NMR δ 5.84 (dd, 1 H, J ) 10.4, 7.9 Hz), 5.76 (d, 1 H, J )
(EtOAc-heptane) gave an analytical sample: mp 155-156 °C;
1
[R]22 -47.8° (c 1.0, CHCl3); H-NMR δ 7.42 (d, 2 H, J ) 8.7
3.4 Hz), 5.57 (dd, 1 H, J ) 10.4, 3.4 Hz), 4.81 (d, 1 H, J ) 8.0
D
Hz), 3.89 (s, 3 H), -0.08 (s, 9 H); HRMS calcd for C33H38O10
SiNa (M + Na): 645.2132, found 645.2128.
-
Hz), 6.88 (d, 2 H, J ) 8.7 Hz), 5.50 (s, 1 H), 4.33 (dd, 1 H, J )
12.5, 1.5 Hz), 4.28 (d, 1 H, J ) 7.3 Hz), 4.18 (dd, 1 H, J ) 3.5,
1.0 Hz), 3.80 (s, 3 H), 3.67 (dd, 1 H, J ) 3.5, 9.7 Hz), 1.05 (m,
2 H), 0.03 (s, 9 H); HRMS calcd for C19H30O7SiNa (M + Na)
421.1659, found 421.1674.
2-(Tr im eth ylsilyl)eth yl 2,3-Di-O-ben zoyl-â-D-ga la cto-
p yr a n osid e (13). To a mixture of compound 2 (50 mg, 0.083
mmol) and CH3CN/H2O (1.5 mL, 9:1) was added DDQ (3.8 mg,
0.017 mmol). The mixture was stirred at 45 °C for 2 h, diluted
with EtOAc (30 mL), washed with aqueous 10% NaHCO3/NaCl
(15 mL), dried (Na2SO4), filtered, and concentrated. The
residue was chromatographed (SiO2, heptane/EtOAc 2:1 f 1:1)
2-(Tr im eth ylsilyl)eth yl 2,3-Di-O-ben zoyl-4,6-O-p-m eth -
oxyben zylid en e-â-D-ga la ctop yr a n osid e (2). Compound 1
(8.00 g, 20.1 mmol) was dissolved in pyridine (120 mL), the
mixture was cooled (ice-water bath), and benzoyl chloride (6.4
mL, 55 mmol) was added dropwise. After 19 h, the mixture
was diluted with CH2Cl2 (500 mL), washed with 2 M H2SO4
(2 × 200 mL), water (2 × 200 mL), saturated aqueous NaHCO3
(200 mL), and water (200 mL), dried (Na2SO4), filtered, and
concentrated. The residue was recrystallized (EtOAc/heptane)
to give 2 (7.41 g, 61%). The mother liquor was concentrated,
and the residue was chromatographed (SiO2, heptane/EtOAc
5:1 f 2:1) to give an additional crop of 2 (3.82 g, 31%): mp
to give 13 (38.1 mg, 97%); [R]22 +74.0° (c 1.0, CHCl3); 1H-
D
NMR δ 5.76 (dd, 1 H, J ) 10.3, 7.9 Hz), 5.30 (dd, 1 H, J )
10.3, 3.1 Hz), 4.74 (d, 1 H, J ) 8.0 Hz), 4.41 (d, 1 H, J ) 2.7
Hz), 3.78 (bt, 1 H, J ) 5.1 Hz), -0.09 (s, 9 H); 13C-NMR δ 166.0,
165.4, 133.4, 133.1, 101.0, 74.6, 74.1, 69.8, 68.2, 67.7, 62.4, 18.0,
-1.5; HRMS calcd for C25H32O8SiNa (M + Na): 511.1764,
found 511.1764.
2-(Tr im eth ylsilyl)eth yl 2,3-Di-O-ben zoyl-6-O-p-m eth -
oxyben zoyl-â-D-glu cop yr a n osid e (14) a n d 2-(Tr im eth yl-
silyl)eth yl 2,3-Di-O-ben zoyl-4-O-p-m eth oxyben zoyl-â-D-
glu cop yr a n osid e (15). Meth od B: Compound 5 (100 mg,
0.17 mmol) was treated with DDQ (58 mg, 0.25 mmol) and
AcOH (14 µL, 0.25 mmol) in the presence of molecular sieves
(nonactivated; no H2O added), as described in the preparation
of 11 and 12. The crude product was chromatographed (SiO2,
heptane/EtOAc 6:1 f 4:1) to give 14 (78 mg, 76%) and 15 (13.7
117-118 °C; [R]22 +130.2° (c 1.0, CHCl3); 1H-NMR δ 7.98 (d,
D
2 H, J ) 8.6 Hz), 6.88 (d, 2 H, J ) 8.6 Hz), 5.85 (dd, 1 H, J )
10.4, 7.9 Hz), 5.50 (s, 1 H), 5.35 (dd, 1 H, J ) 10.5, 3.6 Hz),
4.77 (d, 1 H, J ) 8.1 Hz), 4.57 (d, 1 H, J ) 3.4 Hz), 4.40 (dd,
1 H, J ) 12.3, 1.4 Hz), 3.81 (s, 3 H), 0.90 (m, 2 H), -0.07 (s, 9
H); HRMS calcd for C33H38O9SiNa (M + Na) 629.2183, found
629.2169.
2-(Tr im eth ylsilyl)eth yl 2,3-Di-O-ben zyl-4,6-O-p-m eth -
oxyben zylid en e-â-D-ga la ctop yr a n osid e (3). Compound 1
(1.16 g, 2.9 mmol) was dissolved in DMF (18 mL), NaH (80%,
262 mg, 8.7 mmol) was added, the mixture was stirred for 40
min, benzyl bromide (1.76 mL, 14.6 mmol) was added, and the
mixture was stirred overnight. MeOH (0.5 mL) was added,
and the mixture was stirred for 15 min to destroy unreacted
NaH. The mixture was coconcentrated with toluene-H2O (2:
1, 4 × 5 mL), and the residue was diluted with CH2Cl2 (100
mL). The mixture was washed with saturated aqueous
NaHCO3 (40 mL) and saturated aqueous NaCl (40 mL), dried
(Na2SO4), filtered, and concentrated. The residue was recrys-
tallized (EtOAc/heptane) to give 3 (1.05 g, 62%). The mother
liquor was concentrated, and the residue was chromatographed
(SiO2, heptane/EtOAc 6:1 f 4:1) to give an additional crop of
3 (472 mg, 29%): mp 138-140 °C; [R]22D +30.7° (c 1.0, CHCl3);
1H-NMR δ 5.47 (s, 1 H), 5.35 (dd, 1 H, J ) 10.5, 3.6 Hz), 4.90-
4.75 (m, 4 H), 4.39 (d, 1 H, J ) 7.7 Hz), 4.30 (dd, 1 H, J )
12.2, 1.5 Hz), 3.99 (dd, 1 H, J ) 12.5, 1.7 Hz), 3.81 (s, 3 H),
mg, 13%). Compound 14 had mp 139-140 °C; [R]22 +57.2°
D
(c 1.0, CHCl3); 1H-NMR δ 8.06, 6.95 (d, 2 H each, J ) 9.0 Hz),
5.50-5.39 (m, 2 H), 4.78 (dd, 1 H, J ) 12.1, 4.2 Hz), 4.74 (d,
1 H, J ) 7.7 Hz), 4.61 (dd, 1 H, J ) 12.2, 2.1 Hz), 3.88 (s, 3 H),
3.78 (ddd, 1 H, J ) 9.7, 4.1, 2.2 Hz), 3.50 (d, 1 H, J ) 4.1 Hz),
-0.08 (s, 9 H); HRMS calcd for C33H38O10SiNa (M + Na):
645.2132, found 645.2144. Compound 15 had [R]22D +45.6° (c
0.9, CHCl3); 1H-NMR δ 6.86 (d, 2 H, J ) 9.0 Hz), 5.91 (t, 1 H,
J ) 9.7 Hz), 5.49 (dd, 1 H, J ) 9.9, 7.9 Hz), 5.44 (t, 1 H, J )
9.7 Hz), 4.84 (d, 1 H, J ) 7.9 Hz), 3.83 (s, 3 H), -0.06 (s, 9 H);
HRMS calcd for C33H38O10SiNa (M + Na): 645.2132, found
645.2108.
2-(Tr im eth ylsilyl)eth yl 2,3-Di-O-ben zoyl-â-D-glu cop y-
r a n osid e (16). A mixture of compound 5 (50 mg, 0.083 mmol),
DDQ (3.8 mg, 0.017 mmol), and CH3CN/H2O (1.5 mL, 9:1) was
stirred at 45 °C for 6 h and worked up as described in the
preparation of 13. The residue was chromatographed (SiO2,
heptane/EtOAc 2:1 f 1:1) to give 16 (37.5 mg, 96%); [R]22
D

Oxidation of 4,6-O-Methoxybenzylidene-Protected Saccharides
J . Org. Chem., Vol. 61, No. 7, 1996 2399
+61.0° (c 1.0, CHCl3); 1H-NMR δ 5.46-5.36 (m, 2 H), 4.75 (bd,
1 H, J ) 7.8 Hz), -0.08 (s, 9 H); 13C-NMR 167.6, 165.3, 133.6,
133.2, 100.6, 77.3, 75.7, 71.6, 70.0, 67.8, 62.3, 18.0, -1.5;
HRMS calcd for C25H32O8SiNa (M + Na): 511.1764, found
511.1779.
washed with saturated aqueous NaHCO3 (2 × 20 mL), dried
(Na2SO4), filtered, and concentrated. The residue was chro-
matographed (SiO2, toluene/CH3CN 9:1 f 7:1) to give 25 (53
mg, 65%) and 26 (25 mg, 31%). The physical data for 25 and
26 were as described.16
2-(Tr im et h ylsilyl)et h yl 3-O-Ben zoyl-2-d eoxy-6-O-p -
m eth oxyben zoyl-â-D-glu cop yr a n osid e (17) a n d 2-(Tr i-
m eth ylsilyl)eth yl 3-O-Ben zoyl-2-d eoxy-4-O-p-m eth oxy-
ben zoyl-â-D-glu cop yr a n osid e (18). Meth od C: Compound
6 (779 mg, 1.60 mmol) was treated with DDQ (751 mg, 3.21
mmol) and AcOH (17 µL, 0.48 mmol) in the presence of
molecular sieves (nonactivated; no H2O added), as described
in the preparation of 11 and 12. The crude product was
chromatographed (SiO2, heptane/EtOAc 6:1 f 4:1) to give 17
(553 mg, 66%) and 18 (220 mg, 19%). The physical data for
17 and 18 were as described.17
2-(Tr im et h ylsilyl)et h yl 2-O-Ben zoyl-3-d eoxy-6-O-p -
m eth oxyben zoyl-â-D-glu cop yr a n osid e (19) a n d 2-(Tr i-
m eth ylsilyl)eth yl 2-O-Ben zoyl-3-d eoxy-4-O-p-m eth oxy-
ben zoyl-â-D-glu cop yr a n osid e (20). Meth od D: Compound
7 (150 mg, 0.31 mmol) was treated with DDQ (192 mg, 0.82
mmol) in the presence of molecular sieves (nonactivated; no
AcOH or H2O added), as described in the preparation of 11
and 12. The crude product was treated with AgNO3/KF to
change the 19/20 ratio from 3:2 to 14:1. Chromatography
(SiO2, toluene/CH2Cl2/THF 20:10:3) of the rearranged mixture
gave 19 (132 mg, 85%) and 20 (10 mg, 6%). The physical data
for 19 and 20 were as described.17
2-(Tr im et h ylsilyl)et h yl 2,3-Di-O-b en zoyl-6-ch lor o-6-
deoxy-4-O-p-m eth oxyben zoyl-â-D-galactopyr an oside (27).
Meth od F : A mixture of 2 (200 mg, 0.33 mmol), 18-crown-6
ether (37.2 mg, 0.14 mmol), KCl/4 Å molecular sieves (2.77
mmol/g, 379 mg, ∼1.05 mmol), and dry toluene (5 mL) was
stirred under Ar for 10 min. DDQ (164 mg, 0.70 mmol) was
added, and the mixture was heated at 80 °C overnight. The
mixture was diluted with EtOAc (75 mL), filtered through
Celite, washed with saturated aqueous NaHCO3 (2 × 40 mL)
with vigorous shaking, dried (Na2SO4), filtered, and concen-
trated. The residue was chromatographed (SiO2, heptane/
EtOAc 4:1) to give 27 (179.5 mg, 85%). An analytical sample
was obtained by recrystallization from MeOH; mp 148-149
°C; [R]22 +207.0° (c 1.0, CHCl3); 1H-NMR δ 8.04, 6.95 (d, 2 H
D
each, J ) 9.0 Hz), 5.96 (dd, 1 H, J ) 3.4, 1.0 Hz), 5.77 (dd, 1
H, J )10.5, 8.0 Hz), 5.57 (dd, 1 H, J ) 10.4, 3.4 Hz), 4.83 (d,
1 H, J ) 7.9 Hz), 3.88 (s, 3 H), 3.74-3.64 (m, 3 H), -0.04 (s,
9 H); 13C-NMR δ 165.6, 165.22, 165.17, 163.9, 121.3, 113.9,
101.0, 74.2, 72.0, 69.8, 67.9, 55.5, 41.5, 18.0, -1.5; HRMS calcd
for C33H37O9ClSiNa (M + Na) 663.1793, found 663.1779.
Meth od G: A mixture of 2 (500 mg, 0.82 mmol), DDQ (375
mg, 1.7 mmol), molecular sieves (4 Å, 600 mg), and dry ClCH2-
CH2Cl (10 mL) was stirred for 20 min under Ar, and then
trimethylsilyl chloride (0.209 mL, 1.7 mmol) was added. The
mixture was left at 50 °C overnight and then diluted with
EtOAc (200 mL), filtered throught Celite, washed with satu-
rated aqueous NaHCO3 (2 × 40 mL), dried (Na2SO4), filtered,
and concentrated. The residue was chromatographed (SiO2,
heptane/EtOAc/CH2Cl2 7:1:1) to give 27 (464 mg, 88%).
Meth od H: A mixture of 2 (100 mg, 0.17 mmol), Bu4NCl/
CuCl2 (2:1, 175.8 mg), activated molecular sieves (200 mg),
and dry ClCH2CH2Cl (4 mL) was stirred for 20 min under Ar
and then at 90 °C for 15 h. General workup and purification
as above gave 2 (101 mg, 96%).
2-(Tr im et h ylsilyl)et h yl 2,3-Di-O-b en zoyl-6-b r om o-6-
deoxy-4-O-p-m eth oxyben zoyl-â-D-galactopyr an oside (28).
Meth od I: A mixture of 2 (200 mg, 0.33 mmol), DDQ (112
mg, 0.50 mmol), molecular sieves (4 Å, 200 mg), and dry ClCH2-
CH2Cl (10 mL) was stirred for 20 min, and then trimethylsilyl
bromide (0.067 mL, 0.50 mmol) was added. The mixture was
left at 40 °C for 20 h and then diluted with EtOAc (100 mL),
filtered throught Celite, washed with saturated aqueous
NaHCO3 (2 × 40 mL), dried (Na2SO4), filtered, and concen-
trated. The residue was chromatographed (SiO2, toluene/
EtOAc 80:1 f 10:1) to give 28 (203 mg, 90%). An analytical
sample was obtained by recrystallization from ether/heptane:
mp 143-144 °C; [R]22D +201.2° (c 1.0, CHCl3); 1H-NMR δ 8.04,
6.95 (d, 2 H each, J ) 9.0 Hz), 5.96 (dd, 1 H, J ) 3.4, 1.1 Hz),
5.75 (dd, 1 H, J ) 10.4, 7.8 Hz), 5.54 (dd, 1 H, J ) 9.4, 3.4
Hz), 4.81 (d, 1 H, J ) 7.9 Hz), 3.89 (s, 3 H), 3.52 (dd, 2 H, J )
6.5, 1.2 Hz), -0.04 (s, 9 H); 13C-NMR δ 165.6, 165.23, 165.18,
163.9, 121.2, 113.9, 101.0, 100.9, 74.14, 74.10, 72.0, 69.83,
69.77, 68.4, 67.9, 55.5, 28.8, 18.0, -1.5; HRMS calcd for
C33H37O9SiBrNa (M + Na) 707.1288, found 707.1304.
2-(Tr im eth ylsilyl)eth yl 2,3,6-Tr i-O-ben zoyl-4-O-(2,3-d i-
O-ben zoyl-6-O-p-m eth oxyben zoyl-â-D-ga la ctop yr a n osyl)-
â-D-glu cop yr a n osid e (21) a n d 2-(Tr im et h ylsilyl)et h yl
2,3,6-Tr i-O-ben zoyl-4-O-(2,3-d i-O-ben zoyl-4-O-p-m eth oxy-
ben zoyl-â-D-ga la ctop yr a n osyl)-â-D-glu cop yr a n osid e (22).
Meth od A: Compound 815 (150 mg, 0.14 mmol) was treated
with DDQ (49.5 mg, 0.21 mmol), H2O (5.1 µL, 0.28 mmol),
AcOH (24.2 µL, 0.71 mmol), and nonactivated molecular sieves
(100 mg), as described in the preparation of 11 and 12. The
crude product was chromatagraphed (SiO2, heptane/EtOAc 6:1
f 4:1) to give 21 (121 mg, 79%) and 22 (30 mg, 20%).
Compound 21 had [R]22 +50.6° (c 1.0, CHCl3); 1H-NMR δ
D
5.80-5.69 (m, 2 H), 5.43 (dd, 1 H, J ) 9.6, 7.9 Hz), 5.13 (dd,
1 H, J ) 10.4, 3.2 Hz), 4.77, 4.70 (d, 1 H each, J ) 8.1, 7.9
Hz), 4.60, 4.45 (dd, 1 H each, J ) 12.0, 1.5, 4.7 Hz), 4.20 (t, 1
H, J ) 9.3 Hz), 3.88 (s, 3 H), -0.13 (s, 9 H); HRMS calcd for
C60H60O18SiNa (M + Na): 1119.3447, found 1119.3474. Com-
1
pound 22 had [R]22 +112.9° (c 1.0, CHCl3); H-NMR δ 5.77
D
(dd, 1 H, J ) 10.2, 7.9 Hz), 5.70 (t, 1 H, J ) 9.1 Hz), 5.50 (d,
1 H, J ) 3.4 Hz), 5.44 (dd, 1 H, J ) 9.6, 8.0 Hz), 5.33 (dd, 1 H,
J ) 10.5, 3.4 Hz), 4.81, 4.70 (d, 1 H each, J ) 7.8, 7.8 Hz),
4.59 (bd, 1 H, J ) 12.0 Hz), 4.45 (dd, 1 H, J ) 12.1, 5.0 Hz),
4.18 (t, 1 H, J ) 9.5 Hz), 3.92 (s, 3 H), 2.93, 2.66 (dABq, 1 H
each, J ) 11.8, 6.3 Hz), -0.13 (s, 9 H); HRMS calcd for
C60H60O18SiNa (M + Na): 1119.3447, found 1119.3423.
2-(Tr im eth ylsilyl)eth yl 2,3-Di-O-ben zoyl-6-d eoxy-4-O-
(2,3-d i-O-ben zoyl-6-O-p-m eth oxyben zoyl-â-D-ga la ctop y-
r an osyl)-â-D-glu copyr an oside (23) an d 2-(Tr im eth ylsilyl)-
eth yl 2,3-Di-O-ben zoyl-6-d eoxy-4-O-(2,3-d i-O-ben zoyl-4-
O-p -m et h oxyb en zoyl-â-D-ga la ct op yr a n osyl)-â-D-glu co-
p yr a n osid e (24). Meth od A: Compound 9 (259 mg, 0.27
mmol) was treated with DDQ (134 mg, 0.57 mmol), AcOH (81.5
µL, 1.43 mmol), molecular sieves (250 mg), and H2O (10 µL,
0.57 mmol), as described in the preparation of 11 and 12. The
crude product was chromatographed (SiO2, heptane/EtOAc 3:1
f 1:1) to give 23 (218 mg, 83%) and 24 (43.9 mg, 16%). The
physical data for 23 and 24 were as described.17
Meth od J : A mixture of 2 (200 mg, 0.33 mmol), Bu4NBr/
CuBr2 (2:1, 220 mg), activated molecular sieves (4 Å, 200 mg),
and dry ClCH2CH2Cl (4 mL) was stirred for 20 min under Ar.
DDQ (164 mg, 0.70 mmol) was added, and the mixture was
stirred at 90 °C for 15 h. Workup and purification as above
gave 28 (210 mg, 93%).
2-(Tr im et h ylsilyl)et h yl 2,3,6-Tr i-O-a cet yl-4-O-(2-O-
a cet yl-3-d eoxy-6-O-p -m et h oxyb en zoyl-â-D-xylo-h exop y-
r an osyl)-â-D-glu copyr an oside (25) an d 2-(Tr im eth ylsilyl)-
et h yl 2,3,6-Tr i-O-a cet yl-4-O-(2-O-a cet yl-3-d eoxy-4-O-p -
m e t h oxyb e n zoyl-â-D -xylo-h e xop yr a n osyl)-â-D -glu co-
p yr a n osid e (26). Meth od E: A mixture of 10 (80 mg, 0.112
mmol), DDQ (40 mg, 0.169 mmol), 18-crown-6 ether (3 mg),
NaHSO4 (69 mg, 0.507 mmol), molecular sieves (4 Å) (0.01 mL
H2O added to 200 mg of sieves), and ClCH2CH2Cl (5 mL) was
stirred at 70 °C overnight and then diluted with CH2Cl2/H2O
(70 mL, 5:2) and filtered (Celite). The organic phase was
2-(Tr im et h ylsilyl)et h yl 2,3-Di-O-b en zoyl-6-ch lor o-6-
d eoxy-4-O-p-m eth oxyben zoyl-â-D-glu cop yr a n osid e (29).
Meth od G: Compound 5 (200 mg, 0.33 mmol) was treated with
DDQ (112 mg, 0.50 mmol) and trimethylsilyl chloride (0.063
mL, 0.50 mmol) as described in the preparation of 27 according
to method G. The crude product was chromatographed (SiO2,
toluene/EtOAc 80:1 f 40:1) to give 29 (166 mg, 79%). An
analytical sample was obtained by recrystallization from
ether/heptane: mp 149-151 °C; [R]22 -2.9° (c 1.0, CHCl3);
D
1H-NMR δ 5.86 (t, 1 H, J ) 9.6 Hz), 5.50 (dd, 1 H, J ) 9.8, 7.9
Hz), 5.43 (t, 1 H, J ) 9.6 Hz), 4.86 (d, 1 H, J ) 7.9 Hz), 4.02-

2400 J . Org. Chem., Vol. 61, No. 7, 1996
Zhang and Magnusson
3.95 (m, 1 H), 3.82 (s, 3 H), -0.05 (s, 9 H); HRMS calcd for
C33H37O9SiClNa (M + Na) 663.1793, found 663.1802.
Meth od H: Compound 5 (100 mg, 0.17 mmol) was treated
with DDQ (58 mg, 0.25 mmol), Bu4NCl/CuCl2 (2:1, 176 mg)
and molecular sieves (3 Å, 100 mg) as described in the
preparation of 27 according to method H. Workup and
purification as above gave 9 (96.5 mg, 91%).
2-(Tr im et h ylsilyl)et h yl 2,3-Di-O-b en zoyl-6-b r om o-6-
d eoxy-4-O-p-m et h oxyb en zoyl-â-D-glu cop yr a n osid e (30)
a n d 2-(Tr im eth ylsilyl)eth yl 2,3-Di-O-ben zoyl-6-br om o-6-
d eoxy-5-O-p-m eth oxyben zoyl-r-D-glu cofu r a n osid e (31).
Meth od I: Compound 5 (100 mg, 0.17 mmol) was treated with
DDQ (58 mg, 0.25 mmol) and trimethylsilyl bromide (98%,
0.033 mL, 0.25 mmol) as described in the preparation of 28
according to method I. Workup and purification as above gave
10.3, 3.3 Hz), 4.85 (d, 1 H, J ) 8.0 Hz), 4.71 (d, 1 H, J ) 7.9
Hz), 4.63, 4.44 (dd, 1 H each, J ) 12.2, 1.5, 4.4 Hz), 4.27 (t, 1
H, J ) 9.5 Hz), 3.90 (s, 3 H), 3.66 (t, 1 H, J ) 6.6 Hz), 2.92,
2.74 (dd, 1 H each J ) 11.4, 6.4, 6.8 Hz), -0.13 (s, 9 H); 13C-
NMR δ 165.9, 165.4, 165.2, 164.8, 163.9, 121.1, 113.9, 100.7,
100.4, 75.9, 74.3, 73.3, 72.9, 71.9, 71.8, 69.9, 67.5, 67.3, 62.5,
55.6, 40.5, 17.9, -1.5; HRMS calcd for C60H59O17SiClNa (M +
Na) 1137.3108, found 1137.3126.
2-(Tr im eth ylsilyl)eth yl 2,3,6-Tr i-O-ben zoyl-4-O-(2,3-d i-
O-b en zoyl-6-b r om o-6-d eoxy-4-O-p-m et h oxyb en zoyl-â-D-
ga la ctop yr a n osyl)-â-D-glu cop yr a n osid e (35). Meth od I:
Compound 8 (150 mg, 0.14 mmol) was treated with DDQ (49
mg, 0.22 mmol) and trimethylsilyl bromide (98% 0.0186 mL,
0.14 mmol) in dry chloroform (3 mL) at 50 °C as described in
the preparation of 28 according to method I. The crude
product was chromatographed (SiO2, heptane/EtOAc 3:1) to
give 35 (134 mg, 83%). An analytical sample was obtained
31 (22.1 mg, 20%) and 30 (85.2 mg, 75%). Compound 30:
1
[R]22 -40.0° (c 1.0, CHCl3); H-NMR δ 5.86 (t, 1 H, J ) 9.7
D
by recrystallization from ether/heptane: mp 109-110 °C; [R]22
Hz), 5.50 (dd, 1 H, J ) 9.7, 7.9 Hz), 5.40 (t, 1 H, J ) 9.6 Hz),
4.86 (d, 1 H, J ) 7.8 Hz), 3.98 (m, 1 H), 3.82 (s, 3 H), 3.58 (dd,
1 H, J ) 11.2, 3.4 Hz), 3.53 (dd, 1 H, J ) 11.4, 7.6 Hz), -0.04
(s, 9 H); 13C-NMR δ 165.8, 165.0, 163.9, 120.9, 113.8, 100.4,
74.3, 72.9, 72.1, 71.6, 67.7, 55.4, 31.2, 17.9, -1.5; HRMS calcd
for C33H37O9BrSiNa 707.1288, found 707.1309. Compound
D
1
+101.0° (c 1.0, CHCl3); H-NMR δ 5.79 (t, 1 H, J ) 9.5 Hz),
5.71 (d, 1 H, J ) 2.9 Hz), 5.68 (dd, 1 H, J ) 10.4, 8.0 Hz), 5.47
(dd, 1 H, J ) 9.7, 8.0 Hz), 5.33 (dd, 1 H, J ) 10.3, 3.4 Hz),
4.87 (d, 1 H, J ) 8.0 Hz), 4.72 (d, 1 H, J ) 7.9 Hz), 4.66 (bd,
1 H, J ) 10.7 Hz), 4.46 (dd, 1 H, J ) 12.2, 4.4 Hz), 4.32 (t, 1
H, J ) 9.5 Hz), 3.89 (s, 3 H), 3.74 (t, 1 H, J ) 6.6 Hz), 2.83,
2.58 (dd, 1 H each J ) 10.7, 6.1, 7.1 Hz), -0.12 (s, 9 H). Anal.
Calcd for C60H59O17BrSi: C, 62.1; H, 5.1. Found: C, 61.8; H,
5.5.
Meth od J : Compound 8 (100 mg, 0.093 mmol) was treated
with DDQ (33 mg, 0.14 mmol) and Bu4NBr/CuBr2 (2:1, 123
mg) in dry ClCH2CH2Cl (4 mL) as described in the preparation
of 28 according to method J . Workup and purification as above
gave 35 (100 mg, 93%)
Meth od L:2 A mixture of compound 8 (50 mg, 0.046 mmol),
NBS (15.6 mg, 0.069 mmol), and tetrachloromethane (20 mL)
was heated until ∼2 mL of the solvent was distilled off. The
mixture was refluxed overnight, diluted with chloroform (10
mL), washed with 10% aqueous Na2S2O3 (10 mL), dried (Na2-
SO4), filtered, and concentrated. The residue was chromato-
graphed (SiO2, heptane/EtOAc 3:1) to give 35 (51 mg, 95%).
2-(Tr im eth ylsilyl)eth yl 2,3,6-Tr i-O-ben zoyl-4-O-(2,3-d i-
O-ben zoyl-6-d eoxy-4-O-p-m eth oxyben zoyl-â-D-ga la ctop y-
r a n osyl)-â-D-glu cop yr a n osid e (36). Tributyltin hydride
(0.030 mL, 0.11 mmol) was dissolved in dry toluene (3 mL)
and the mixture was brought to reflux. A solution of compound
35 (50 mg, 0.043 mmol) and azobis(isobutyronitrile) (AIBN, 1
mg) in dry toluene (1 mL) was added under Ar. The mixture
was refluxed for 5 h and concentrated. The residue was
chromatographed (SiO2, heptane/EtOAc/acetone 8:2:1) to give
36 (46 mg, 99%): [R]22D +123.1° (c 1.0, CHCl3); 1H-NMR δ 5.77
(t, 1 H, J ) 9.3 Hz), 5.67 (dd, 1 H, J ) 10.3, 7.8 Hz), 5.45-
5.38 (m, 2 H), 5.31 (dd, 1 H, J ) 10.3, 3.3 Hz), 4.80 (d, 1 H, J
) 7.9 Hz), 4.71 (d, 1 H, J ) 7.8 Hz), 4.59, 4.45 (dd, 1 H each,
J ) 11.9, 1.6, 4.6 Hz), 4.19 (t, 1 H, J ) 9.2 Hz), 3.89 (s, 3 H),
0.64 (d, 3 H, J ) 6.4 Hz); HRMS calcd for C60H60O17SiNa (M
+ Na) 1103.3497, found 1103.3466.
31: [R]22 -35.4° (c 1.0, CHCl3); 1H-NMR δ 5.88 (dd, 1 H, J )
D
5.6, 1.0 Hz), 5.51 (dt, 1 H, J ) 9.2, 2.8 Hz), 5.43 (d, 1 H, J )
1.2 Hz), 5.26 (s, 1 H), 5.01 (dd, 1 H, J ) 9.2, 5.5 Hz), 4.03 (dd,
1 H, J ) 11.5, 3.0 Hz), 3.83 (s, 3 H), 3.64 (m, 1 H), 0.04 (s, 9
H); 13C-NMR 165.1, 165.0, 164.7, 163.6, 121.5, 113.5, 106.0,
81.3, 79.0, 74.5, 69.6, 66.3, 55.4, 33.9, 18.0, -1.3; HRMS calcd
for C33H37O9SiBrNa (M + Na) 707.1288, found 707.1309.
Meth od J : Compound 5 (100 mg, 0.17 mmol) was treated
with DDQ (58 mg, 0.25 mmol) and Bu4NBr/CuBr2 (2:1, 220
mg) as described in the preparation of 28 according to method
J . Workup and purification as above gave 30 (99.3 mg, 88%).
2-(Tr im et h ylsilyl)et h yl 2,3-Di-O-b en zyl-6-b r om o-6-
d eoxy-4-O-p-m eth oxyben zoyl-â-D-ga la ctop yr a n osid e (32)
a n d 2-(Tr im eth ylsilyl)eth yl 2-O-Ben zyl-6-br om o-6-d eoxy-
4-O-p-m eth oxyben zoyl-â-D-ga la ctop yr a n osid e (33). Com-
pound 3 (100 mg, 0.17 mmol) was treated with DDQ (80 mg,
0.35 mmol) and trimethylsilyl bromide (0.040 mL, 0.31 mmol)
in dry chloroform (8 mL) at 60 °C for 2 h, essentially as
described in the preparation of 28 according to method B. The
crude product was chromatographed (SiO2, heptane/EtOAc 4:1)
to give 32 (38 mg, 33%) and 33 (52 mg, 53%). Compound 32:
[R]22D +55.1° (c 1.0, CHCl3); 1H-NMR δ 8.06, 6.93 (d, 2 H each,
J ) 9.0 Hz), 5.83 (t, 1 H, J ) 1.3 Hz), 4.94-4.57 (m, 4 H), 4.48
(bd, 1 H, J ) 7.6 Hz), 4.10 (m, 1 H), 3.81 (dt, 1 H, J ) 6.6, 1.0
Hz), 3.44 (dd, 2 H, J ) 6.7, 1.3 Hz), 0.05 (s, 9 H); 13C-NMR δ
165.5, 163.7, 138.6, 137.8, 121.8, 113.7, 103.3, 79.3, 78.8, 75.3,
73.8, 72.0, 67.9, 67.4, 55.5, 29.4, 18.5, -1.4. Anal. Calcd for
C33H41O7BrSi: C, 60.4; H, 6.3. Found: C, 60.7; H, 6.3.
1
Compound 33: [R]22 +46.5° (c 1.5, CHCl3); H-NMR δ 8.05,
D
6.92 (d, 2 H each, J ) 9.0 Hz), 5.85 (bd, 1 H, J ) 3.2 Hz), 4.88,
4.54 (d, 1 H each, J ) 11.5 Hz), 4.39 (d, 1 H, J ) 7.8 Hz), 4.08
(m, 1 H), 3.86 (s, 3 H), 3.57 (dd, 1 H, J ) 9.7, 3.3 Hz), 3.45 (d,
1 H, J ) 6.7 Hz), 0.04 (s, 9 H); 13C-NMR δ 165.5, 163.8, 137.4,
121.6, 113.7, 102.5, 79.1, 74.1, 71.7, 70.7, 67.69, 66.7, 55.5, 29.3,
18.2, -1.4; HRMS calcd for C26H35O7SiBrNa (M + Na) 589.1233,
found 589.1233.
Ack n ow led gm en t. This work was supported by the
Swedish Natural Science Research Council. We are
grateful to Mr. Krister So¨dergren for technical as-
sistance.
2-(Tr im eth ylsilyl)eth yl 2,3,6-Tr i-O-ben zoyl-4-O-(2,3-d i-
O-b en zoyl-6-ch lor o-6-d eoxy-4-O-p -m et h oxyb en zoyl-â-D-
ga la ctop yr a n osyl)-â-D-glu cop yr a n osid e (34). Meth od H:
Compound 8 (150 mg, 0.14 mmol) was treated with DDQ (49
mg, 0.22 mmol) and trimethylsilyl chloride (0.0277 mL, 0.22
mmol) in dry chloroform (4 mL) at 55 °C, as described in the
preparation of 27 according to method B. The crude product
was chromatographed (SiO2, heptane/EtOAc 8:3) to give 34
(151 mg, 97%). An analytical sample was obtained by recrys-
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra
and 1H NMR data with peak assignments for all title com-
pounds described in the Experimental Section (34 pages). This
material is contained in libraries on microfiche, immediately
follows this article in the microfilm version of the journal, and
can be ordered from the ACS; see any current masthead page
for ordering information.
tallization from ether/heptane: mp 100-102 °C; [R]22 +113°
D
(c 0.7, CHCl3); 1H-NMR δ 5.77 (t, 1 H, J ) 9.6 Hz), 5.70-5.64
(m, 2 H), 5.45 (dd, 1 H, J ) 9.7, 8.0 Hz), 5.30 (dd, 1 H, J )
J O952177V