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The synthesis of 2-azido C-glycosyl sugars
Teuahedmn Lam, Vol. 33, No. 22, pp.31W3112. 1992 Printed in Great Iiritain
THE
SYNTHESIS
OF Z-AZIDO
C-GLYCOSYL
SUGARS
Carolyn R. Bertozzi and Mark D. Bednarski*
Department
of Chemistry,
University of California, Berkeley, CA 94720
&mmaty: 2-Azido C-glycosyl sugars can be prepared by the Lewis acid catalyzed addition of alkyl silanesto the nitrateglycosidesof 2-azido sugars. The products are ozoniti to the coPrespondingaldehyddesfor further elaboration Amino sugarsare integral components biological
recognition
phenomena.
agents4
linked to serine or threonine
of these sugars can serve as stable analogs for biological recognition
generation of more complex carbohydrate
of 2-amino C-glycosyl
One of the most direct routes to a-linked
with these conditions.6
therefore fmussed
on opening
followed by cyclization approach
These methods,
which are incompatible In our efforts
C-glycosyl
product.6-*
the hetero 14+2] cycloaddition
of azo compounds
biologically
active C-glycosides,
of these compounds
a
glycals.9
compounds
an efficient
method
for the
is masked during the synthesis as an
Azides are ideal amine equivalents and the ease of reduction in carbohydrate
have been limited IO simple anomeric cyanides.l
of 2-azido a-C-glycosyl
due to their non-
to the corresponding chemistry,
C-gly~o~yl
1 We report herein a method for
by the direct Lewis acid catalyzed
addition of alkyl silanes to
of 2-azido sugars.
We first investigated
the addition reaction of allyltrimethylsilane
were prepared by azidonitration M solution in C‘fl$N)
have recently described
with C-l substituted
we required
sugars in which the amine functionality
their stability under acidic and basic conditions,
the nitrate glycosides
at C-
sugars have
reaction or vinylation reaction
Leblanc and coworkers
amine.10 Despite the fact that 2-azido sugars have been used extensively the synthesis
the Lewis acid catalyzed
amino and amido substituents
with Lewis acidic and anionic conditions and limit subsequent derivatization. to synthesize
unreactive group towards Lewis acids and anionic reagents.
derivatives
involves
involve several steps resulting in products that contain amine or amide functionalities
preparation of 2-amino a-C-glycosyl
nucleophilicity,
compounds
derivatives. 5 Unfortunately,
the pyranose or furanose ring by either a Wittig-type
involving
active
are therefore necessary for the
Previous methods for the synthesis of 2-amino C-glycosyl
to provide the C-glycosyl
however,
studies or as biologically
compounds
are
C-glycosyl
analogs such as glycopeptides.
addition of alkyd silanes to activated carbohydrate 2 are incompatible
with crucial roles in
such as the blood group and tumor associated antigens.2,3
Efficient methods for the construction
different
a class of natural products
* For example, 2=acetamido a-galactosides
commonly found in O-linked glycopeptides derivatives
of glycoproteins,
of the corresponding
tri-i)-henzyl
to compounds
were. treated with 1.5 equivalents of allyltrimethylsilane
0 DC for 16 h to afford a 5;1 mixture of a/lJ C-glycosyl
propenes
3109
1 and 2 (Scheme 1’)which
glycals. 1Qb,1%12 Both compounds and 1.1 equivalents
3 and 4. Both compounds
1 and 2 (1
of BF@Et2 at
3 and 4, however,
3110
react readily at room temperature products
to afford the unwanted
3 and 4 were used without purification
temperatures
(c -20 “C).
triethylamine
provided,
Ozonolysis
purification
the crude
workup and were stored at reduced
3 and 4 in CH2C12 at -78 “C followed
aldehydes 7 and 8 in ca. 40 % overall yield from compounds
Scheme
adducts 5 and 6.’ 3 Therefore,
after careful extractive
of compounds
after chromatographic
1,3-dipolar
(IO:1 hexanes/ethyl
by reduction
acetate),
with
the stable a-linked
1 and 2.14
I
5: X = H. Y = OBn 6: X = OBn, Y = H
BF.OEt.
l:X=H,Y=OBn
3:X=H,Y=OBn 4: X = OBn, Y = H
2:X=OBn,Y=H
7: X = H, Y = OBn 8: X = OBn. Y = H
Alternatively, CQtX5ponding
aldehydes
7 and 8 can be generated
acetate glycosides
with 3 equivalents
of compounds
by a similar reaction
1 and 2 which were prepared
sequence
by reaction
starting
with the
of the nitrate sugars
of NaOAc in acetic acid at 100 “C for 8 h, In this case, however, the less reactive acetate
derivatives required 3 equivalents of BF30Et2 and a reaction time of 48 h at 0 “C. When methyl 2-azido-2-deoxy(3,4,6-tri-Gbenzyl)-P-D-glucopyranoside Lewis acids (BFlOEtZ,
TMSOTf,
was reacted with allyltrimethylsilane Tick,
SnC4)
no reaction
was observed.
in the presence Therefore,
of a variety of
unlike the methyl
glycosides of 2-alkoxy sugars, the methyl glycosides of 2-azido sugars are unreactive under the normal conditions for Lewis acid catalyzed C-glycosylation Compound
2
pmpargyltrimethylsilane the corresponding
and 1.1 equivalents
a-C-glycosyl
allene 9 is sufficiently
aldehyde
temperatures.
in CH3CN)
can
also
be
reacted
of BF30Et2 at 0 “C to room temperature
with
1.5
equivalents
of
over a 10 h period to afford
allene 9 in 65 % yield (Scheme II). 153th Unlike Ihe ally1 derivatives
stable at room temperature
Compound 9 decomposes reduced
reactions.
(1 M solution
to be purified by silica gel chromatography
3 and 4, the
(7: 1 pentane/ether).
to several products, however, after two weeks at 0 “C and should therefore be stored at Ozonolysis
10.17 Compound
of compound
10 readily undergoes
9 in CH2C12 at -78 “C provides p-elimination
temperature and must be used without further purification.
quantitatively
of the azide upon exposure
the sensitive
to silica gel at room
3111
Scheme II
In summary, Aldehydes
we have described
an efficient
method for the preparation
8 and 10 have been used as substrates for aldol condensations
can be further derivatized
to afford a variety of electrophilic
glycosyl products can be effected with thiolacetic naturally occurring
sugars.~9
We are currently
of 2-azido C-glycosyl
and Wittig reactions,
substrates.
Reductive
respectively,
acetylation
acid’8 to provide the corresponding investigating
and
of the 2-azido C-
2-acetarnido
the utility of these compounds
sugars.
analogs of the
in the synthesis
of
stable analogs of complex oligosaccharides.
Acknowledgement. The authors thank the American Cancer Society for a Junior Faculty Investigator
Award (M. B.) and an ACS Medicinal
Chemistry
for a GRPW grant (C, B.), This research was supported
Award (M. B.), Eli Lilly for a Junior
Fellowship
(C. B,) and AT&T Bell Laboratories
by National Institute of Health awrard # R29 GM43037-
02.
References 1.
and Notes.
For reviews sez the following. .ki.
1980.37.
Chem, Biochem.
(a) Paulson, J. C. Trends Biochem. Sci. 1989, 14, 272. (b) lentoft. N. Trends Biochem,
(c) Kunz, H. Angew
1990,15,291.
Chem. Inl. Ed. Engl.
1987.26,
Kabat, E. A. In Blood and Tissue Antigens
3.
Springer, G. F. Science
4.
C-glycosyl compounds have been used previously as stable, biologically
1984.224,
1198.
Sinnoll, M. L.; Smith, P. J.
active analogs of naturally occurring oxygen-linked
V. N.; Myers, R. W.; Carbohydr.
Norbeck, D. W.; Kramer, J. B.; Lartey, P. A.; J. Org. Ckm. P. K. /. Med. Chem. 19X4.27,
1987,X,
2174.
J. Chem. See., Chem. Commun.
Ann. Chem.
1989,357.
1976,223.
(g) Giannis, A.; Sandhoff,
Res. 1990,200,
2383.
described.
,4llvltrimethvlsil~
(b) Hosomi, A.; S&&t,
J. Am, C&m. Sot.
(‘b)
Lett.
1978,8,
(0 Kuhn, C. -S.; Glaudemans, K. Tetrahedron
Letr.
1991,30,
723.
(e)
C. P. J.:
1985, 26, 1479, Rts.
(h)
1986,
1328. (k) Bertoezi. C. R.; Bednarski,
Res. 1992,223,243,,
Lewis acid catalyzed additions of alkyl silanes to activated carbohydrate been previously
111,
(c) Meyer, R. B., Jr.; Stone, T. E.; Jesthi,
391, (i) Myers, R. W.; Lee. Y. C. Carbohydr.
lS2, 143. (‘j) Schmidt, R. R.: Diemich, H. Angew. Chem. Int. Ed. Engl.
5.
Res. 1990,200.
1095. (d) Tang, 1. -C.; Tropp, B. E.; Engel, R. Tetrahedron
Svensson. S. C. T.; Thiem, J. Carbohydr.
M. D. Carbohydr.
Cnrbohydr.
Aminoff, D., Ed., Academic Press: New York, 1970.
(a) BeMiller, J. N.; Yadav, M, P.; Kalabokis,
Lehmann, J. Liebigs
(d) Montreuil, J. Adv.
157.
2.
sugars.
294.
1982,104,
Y.; Sakurai, H. Carbohydr, 4976.
derivatives to provide the a-C-glycosyl
. (a) Hosomi. A.: Sakata, Y.; Sakurai, H,
(d) Danishefsky,
Res. 1987,171,
223.
S.: Kerwin, J, F,, Jr.
Tetrahedron
produet have
Lerr.
1984,X,
(c) Lewis, M. D.; Cha, J. K.; Kishi, Y.
d. Org. Chem.
1982.47.
3803.
{e)
3112
Kozikowski,
A. P.; Sorgi, K. L.: Wang, B. C.: Xu, Z. Tetrahedron
Terrahedron Left.
1985,26,
1479.
Chem. 1987.52.
1370.
2034. EconarevlVimetkvlsilane:
(j) Pornet, J.: Miginiac, L.: Jaworski,
333. (k) Bruckner, C.: Holzinger, H.; Reissig, H. U. J. Org. C&t.
1988,53,
Carcano,
I.
Nicotra, F.; Russo, G.; Ronchetti, F.; Toma, L. Carbnhydr. Rex
8.
Giannis, A.; Sandhoff, K. Carbahydr. Rex. 1987.171,201.
9.
Grondin. R.; Leblanc, Y.; Hoogsteen, K. Tetrahedron Left. 199L32.5021.
10.
For examples of the use of azido sugars in carbohydrate Chem. Inr. Ed. EnRl. 1990,29,
1985,4,
1989, 297.
C5.
chemistry see the following.
(a) Revicwcd in ref. Ic and in Paulsen,
(b) Kinzy, W.; Schmidt, R. R. Liebi8.s Ann. Gem.
1985, 1537. (c)
G.; Schmidt_ R. R. Liebigs Ann. Chem. 1984, 1826. (d) Sahefian, S.; Lemieux, R. U. Can. .I. Chem. 1984,
62, 644.
(e) Marra. A.; Shun, L. K. S.: Gauffeny,
Hakomori,
S. Tetrahedron
A. Tetrahedron
Lert. 1990,31,2673.
F.; Sinaji. P.
Synlert
(g) Kunz;, H.; Bimbach,
1990,
445.
(f, Toyokuni,
S.; Wemig, P. Corbohydr.
Y.; lijima, H.; Sibayama, S,; Ogawa, T, Tetrahedron Lerr. 1990,31,
1985,41,
T.; Dean, B.;
Rex
1990,202,
6897. (i) Ferrari, B.: Pavia, A.
1939. (i) Paulsen, H.; Paal, M. Carbohydr. Res. 1984,135,71.
(a) BcMillcr, J, N.; Blazis, V. J.; Myers, R. W. 1. Curbohydr. Chem. 1990,9, 39. (b) Hoffmann, M. G.; Schmidt, R. R. Liebigs Ann. Chem.
12.
B. Organame&zllics
Grundler,
207. (h) Nakahara,
11.
823.
(h) Panek, J.
2450,
M.: Nicotra, F.; Panza, L.; Russo, G. J Chem. Sot., Chem. Cammun. 1983,124,
5627.
(i) Babirad, S. A.: Wang, Y.; Kishi, Y. J.
K.; Randrianoelina,
6.
H. Anpw.
1563. (f) Giannis, A.: Sandhoff, K.
(g) Nicotra, F.; Panza. L.; Russo, G. J. Org. C/rem. 1987.52,
S.; Sparks. M. A. J. Org. Chem. 1989.54. org.
L&t. 1983,24,
The azidonitration and coworkers
1985, 2403.
procedure used for the synthesis of compounds 1 and 2 is a modified version of that described by Schmidt
(refs. lob and 1oC). A solution of the 3,4,6-tri-0-benzyl
glycal in acemnitrile (0.1 M) was cooled to -23 “C
and treated with 1.6 equivalents of NaN3 and 3 equivalent7 of c&urn ammonium nitrate (CAN). The suspension was stir& for 2.5 h and then poured into ice water and diluted with ether. The organic layer was separated, washed with water and brine and dried over MgSO4, The crude product was purified by silica gel chromata$Taphy eluting with 15:l hcxancs/ethyl acetate, 13.
The inwmolwfar
1,3-dipolar addition is complete after 12 h ar rwm temperature.
NMR, IR and mass spectromcuy
without assignment of tbe sterwchemistry
Dipolar adducts were characterized
of the bridgehead carbon atom.
14.
The fl-linked aldchydc was not isolated but can be easily separated from the n-linked &tier
15.
The acetate glycoside
cm
also be
used
The reaction is warmed to room temperature over a 12 h p&xl,
17,
another 1.0
are added and then tbe reaction is continued for another 12 h. In this case, however,
only ca. 50 % of the acetate glycoside reacts and Ihe yield of compound 9 is significantly 16.
by silica gel chromatography.
as a substrate far the synthesis of allene 9 in which case the reaction is started at 0 OC
with 1.5 equivalents of propargyltrimethylsilane. equivalents of propargyltimethylsilanc
by
lower.
Only the a-linked diastereomer was observed by NMR. We have recently described a method for the synthesis of C-glycosyl aldehydes via ozonolysis of C-glycosyl allcncs. Kob&~, W. R.; Benozzi, C. R.; Bednarski, M. D. Tetrahedron Lett. 1992,33, 734.
1X. 19.
Rosen, T.; Lice, I. M.; Chu, D. T. W. J. Org. Chem. 1988,53,
1580.
Some other methods for the direct reductive acetylation of 2-azido sugars are described in: (a) Paulsen, H.; Adermann, K. Lie&
(Received
Ann. Chem.
1989, 751. (b) Ref lob.
in USA 19 February
1992)
(c) Ciommer, M.; Kunz, H, Synlert
1991, 593.
THE
SYNTHESIS
OF Z-AZIDO
C-GLYCOSYL
SUGARS
Carolyn R. Bertozzi and Mark D. Bednarski*
Department
of Chemistry,
University of California, Berkeley, CA 94720
&mmaty: 2-Azido C-glycosyl sugars can be prepared by the Lewis acid catalyzed addition of alkyl silanesto the nitrateglycosidesof 2-azido sugars. The products are ozoniti to the coPrespondingaldehyddesfor further elaboration Amino sugarsare integral components biological
recognition
phenomena.
agents4
linked to serine or threonine
of these sugars can serve as stable analogs for biological recognition
generation of more complex carbohydrate
of 2-amino C-glycosyl
One of the most direct routes to a-linked
with these conditions.6
therefore fmussed
on opening
followed by cyclization approach
These methods,
which are incompatible In our efforts
C-glycosyl
product.6-*
the hetero 14+2] cycloaddition
of azo compounds
biologically
active C-glycosides,
of these compounds
a
glycals.9
compounds
an efficient
method
for the
is masked during the synthesis as an
Azides are ideal amine equivalents and the ease of reduction in carbohydrate
have been limited IO simple anomeric cyanides.l
of 2-azido a-C-glycosyl
due to their non-
to the corresponding chemistry,
C-gly~o~yl
1 We report herein a method for
by the direct Lewis acid catalyzed
addition of alkyl silanes to
of 2-azido sugars.
We first investigated
the addition reaction of allyltrimethylsilane
were prepared by azidonitration M solution in C‘fl$N)
have recently described
with C-l substituted
we required
sugars in which the amine functionality
their stability under acidic and basic conditions,
the nitrate glycosides
at C-
sugars have
reaction or vinylation reaction
Leblanc and coworkers
amine.10 Despite the fact that 2-azido sugars have been used extensively the synthesis
the Lewis acid catalyzed
amino and amido substituents
with Lewis acidic and anionic conditions and limit subsequent derivatization. to synthesize
unreactive group towards Lewis acids and anionic reagents.
derivatives
involves
involve several steps resulting in products that contain amine or amide functionalities
preparation of 2-amino a-C-glycosyl
nucleophilicity,
compounds
derivatives. 5 Unfortunately,
the pyranose or furanose ring by either a Wittig-type
involving
active
are therefore necessary for the
Previous methods for the synthesis of 2-amino C-glycosyl
to provide the C-glycosyl
however,
studies or as biologically
compounds
are
C-glycosyl
analogs such as glycopeptides.
addition of alkyd silanes to activated carbohydrate 2 are incompatible
with crucial roles in
such as the blood group and tumor associated antigens.2,3
Efficient methods for the construction
different
a class of natural products
* For example, 2=acetamido a-galactosides
commonly found in O-linked glycopeptides derivatives
of glycoproteins,
of the corresponding
tri-i)-henzyl
to compounds
were. treated with 1.5 equivalents of allyltrimethylsilane
0 DC for 16 h to afford a 5;1 mixture of a/lJ C-glycosyl
propenes
3109
1 and 2 (Scheme 1’)which
glycals. 1Qb,1%12 Both compounds and 1.1 equivalents
3 and 4. Both compounds
1 and 2 (1
of BF@Et2 at
3 and 4, however,
3110
react readily at room temperature products
to afford the unwanted
3 and 4 were used without purification
temperatures
(c -20 “C).
triethylamine
provided,
Ozonolysis
purification
the crude
workup and were stored at reduced
3 and 4 in CH2C12 at -78 “C followed
aldehydes 7 and 8 in ca. 40 % overall yield from compounds
Scheme
adducts 5 and 6.’ 3 Therefore,
after careful extractive
of compounds
after chromatographic
1,3-dipolar
(IO:1 hexanes/ethyl
by reduction
acetate),
with
the stable a-linked
1 and 2.14
I
5: X = H. Y = OBn 6: X = OBn, Y = H
BF.OEt.
l:X=H,Y=OBn
3:X=H,Y=OBn 4: X = OBn, Y = H
2:X=OBn,Y=H
7: X = H, Y = OBn 8: X = OBn. Y = H
Alternatively, CQtX5ponding
aldehydes
7 and 8 can be generated
acetate glycosides
with 3 equivalents
of compounds
by a similar reaction
1 and 2 which were prepared
sequence
by reaction
starting
with the
of the nitrate sugars
of NaOAc in acetic acid at 100 “C for 8 h, In this case, however, the less reactive acetate
derivatives required 3 equivalents of BF30Et2 and a reaction time of 48 h at 0 “C. When methyl 2-azido-2-deoxy(3,4,6-tri-Gbenzyl)-P-D-glucopyranoside Lewis acids (BFlOEtZ,
TMSOTf,
was reacted with allyltrimethylsilane Tick,
SnC4)
no reaction
was observed.
in the presence Therefore,
of a variety of
unlike the methyl
glycosides of 2-alkoxy sugars, the methyl glycosides of 2-azido sugars are unreactive under the normal conditions for Lewis acid catalyzed C-glycosylation Compound
2
pmpargyltrimethylsilane the corresponding
and 1.1 equivalents
a-C-glycosyl
allene 9 is sufficiently
aldehyde
temperatures.
in CH3CN)
can
also
be
reacted
of BF30Et2 at 0 “C to room temperature
with
1.5
equivalents
of
over a 10 h period to afford
allene 9 in 65 % yield (Scheme II). 153th Unlike Ihe ally1 derivatives
stable at room temperature
Compound 9 decomposes reduced
reactions.
(1 M solution
to be purified by silica gel chromatography
3 and 4, the
(7: 1 pentane/ether).
to several products, however, after two weeks at 0 “C and should therefore be stored at Ozonolysis
10.17 Compound
of compound
10 readily undergoes
9 in CH2C12 at -78 “C provides p-elimination
temperature and must be used without further purification.
quantitatively
of the azide upon exposure
the sensitive
to silica gel at room
3111
Scheme II
In summary, Aldehydes
we have described
an efficient
method for the preparation
8 and 10 have been used as substrates for aldol condensations
can be further derivatized
to afford a variety of electrophilic
glycosyl products can be effected with thiolacetic naturally occurring
sugars.~9
We are currently
of 2-azido C-glycosyl
and Wittig reactions,
substrates.
Reductive
respectively,
acetylation
acid’8 to provide the corresponding investigating
and
of the 2-azido C-
2-acetarnido
the utility of these compounds
sugars.
analogs of the
in the synthesis
of
stable analogs of complex oligosaccharides.
Acknowledgement. The authors thank the American Cancer Society for a Junior Faculty Investigator
Award (M. B.) and an ACS Medicinal
Chemistry
for a GRPW grant (C, B.), This research was supported
Award (M. B.), Eli Lilly for a Junior
Fellowship
(C. B,) and AT&T Bell Laboratories
by National Institute of Health awrard # R29 GM43037-
02.
References 1.
and Notes.
For reviews sez the following. .ki.
1980.37.
Chem, Biochem.
(a) Paulson, J. C. Trends Biochem. Sci. 1989, 14, 272. (b) lentoft. N. Trends Biochem,
(c) Kunz, H. Angew
1990,15,291.
Chem. Inl. Ed. Engl.
1987.26,
Kabat, E. A. In Blood and Tissue Antigens
3.
Springer, G. F. Science
4.
C-glycosyl compounds have been used previously as stable, biologically
1984.224,
1198.
Sinnoll, M. L.; Smith, P. J.
active analogs of naturally occurring oxygen-linked
V. N.; Myers, R. W.; Carbohydr.
Norbeck, D. W.; Kramer, J. B.; Lartey, P. A.; J. Org. Ckm. P. K. /. Med. Chem. 19X4.27,
1987,X,
2174.
J. Chem. See., Chem. Commun.
Ann. Chem.
1989,357.
1976,223.
(g) Giannis, A.; Sandhoff,
Res. 1990,200,
2383.
described.
,4llvltrimethvlsil~
(b) Hosomi, A.; S&&t,
J. Am, C&m. Sot.
(‘b)
Lett.
1978,8,
(0 Kuhn, C. -S.; Glaudemans, K. Tetrahedron
Letr.
1991,30,
723.
(e)
C. P. J.:
1985, 26, 1479, Rts.
(h)
1986,
1328. (k) Bertoezi. C. R.; Bednarski,
Res. 1992,223,243,,
Lewis acid catalyzed additions of alkyl silanes to activated carbohydrate been previously
111,
(c) Meyer, R. B., Jr.; Stone, T. E.; Jesthi,
391, (i) Myers, R. W.; Lee. Y. C. Carbohydr.
lS2, 143. (‘j) Schmidt, R. R.: Diemich, H. Angew. Chem. Int. Ed. Engl.
5.
Res. 1990,200.
1095. (d) Tang, 1. -C.; Tropp, B. E.; Engel, R. Tetrahedron
Svensson. S. C. T.; Thiem, J. Carbohydr.
M. D. Carbohydr.
Cnrbohydr.
Aminoff, D., Ed., Academic Press: New York, 1970.
(a) BeMiller, J. N.; Yadav, M, P.; Kalabokis,
Lehmann, J. Liebigs
(d) Montreuil, J. Adv.
157.
2.
sugars.
294.
1982,104,
Y.; Sakurai, H. Carbohydr, 4976.
derivatives to provide the a-C-glycosyl
. (a) Hosomi. A.: Sakata, Y.; Sakurai, H,
(d) Danishefsky,
Res. 1987,171,
223.
S.: Kerwin, J, F,, Jr.
Tetrahedron
produet have
Lerr.
1984,X,
(c) Lewis, M. D.; Cha, J. K.; Kishi, Y.
d. Org. Chem.
1982.47.
3803.
{e)
3112
Kozikowski,
A. P.; Sorgi, K. L.: Wang, B. C.: Xu, Z. Tetrahedron
Terrahedron Left.
1985,26,
1479.
Chem. 1987.52.
1370.
2034. EconarevlVimetkvlsilane:
(j) Pornet, J.: Miginiac, L.: Jaworski,
333. (k) Bruckner, C.: Holzinger, H.; Reissig, H. U. J. Org. C&t.
1988,53,
Carcano,
I.
Nicotra, F.; Russo, G.; Ronchetti, F.; Toma, L. Carbnhydr. Rex
8.
Giannis, A.; Sandhoff, K. Carbahydr. Rex. 1987.171,201.
9.
Grondin. R.; Leblanc, Y.; Hoogsteen, K. Tetrahedron Left. 199L32.5021.
10.
For examples of the use of azido sugars in carbohydrate Chem. Inr. Ed. EnRl. 1990,29,
1985,4,
1989, 297.
C5.
chemistry see the following.
(a) Revicwcd in ref. Ic and in Paulsen,
(b) Kinzy, W.; Schmidt, R. R. Liebi8.s Ann. Gem.
1985, 1537. (c)
G.; Schmidt_ R. R. Liebigs Ann. Chem. 1984, 1826. (d) Sahefian, S.; Lemieux, R. U. Can. .I. Chem. 1984,
62, 644.
(e) Marra. A.; Shun, L. K. S.: Gauffeny,
Hakomori,
S. Tetrahedron
A. Tetrahedron
Lert. 1990,31,2673.
F.; Sinaji. P.
Synlert
(g) Kunz;, H.; Bimbach,
1990,
445.
(f, Toyokuni,
S.; Wemig, P. Corbohydr.
Y.; lijima, H.; Sibayama, S,; Ogawa, T, Tetrahedron Lerr. 1990,31,
1985,41,
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(a) BcMillcr, J, N.; Blazis, V. J.; Myers, R. W. 1. Curbohydr. Chem. 1990,9, 39. (b) Hoffmann, M. G.; Schmidt, R. R. Liebigs Ann. Chem.
12.
B. Organame&zllics
Grundler,
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6.
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(g) Nicotra, F.; Panza. L.; Russo, G. J. Org. C/rem. 1987.52,
S.; Sparks. M. A. J. Org. Chem. 1989.54. org.
L&t. 1983,24,
The azidonitration and coworkers
1985, 2403.
procedure used for the synthesis of compounds 1 and 2 is a modified version of that described by Schmidt
(refs. lob and 1oC). A solution of the 3,4,6-tri-0-benzyl
glycal in acemnitrile (0.1 M) was cooled to -23 “C
and treated with 1.6 equivalents of NaN3 and 3 equivalent7 of c&urn ammonium nitrate (CAN). The suspension was stir& for 2.5 h and then poured into ice water and diluted with ether. The organic layer was separated, washed with water and brine and dried over MgSO4, The crude product was purified by silica gel chromata$Taphy eluting with 15:l hcxancs/ethyl acetate, 13.
The inwmolwfar
1,3-dipolar addition is complete after 12 h ar rwm temperature.
NMR, IR and mass spectromcuy
without assignment of tbe sterwchemistry
Dipolar adducts were characterized
of the bridgehead carbon atom.
14.
The fl-linked aldchydc was not isolated but can be easily separated from the n-linked &tier
15.
The acetate glycoside
cm
also be
used
The reaction is warmed to room temperature over a 12 h p&xl,
17,
another 1.0
are added and then tbe reaction is continued for another 12 h. In this case, however,
only ca. 50 % of the acetate glycoside reacts and Ihe yield of compound 9 is significantly 16.
by silica gel chromatography.
as a substrate far the synthesis of allene 9 in which case the reaction is started at 0 OC
with 1.5 equivalents of propargyltrimethylsilane. equivalents of propargyltimethylsilanc
by
lower.
Only the a-linked diastereomer was observed by NMR. We have recently described a method for the synthesis of C-glycosyl aldehydes via ozonolysis of C-glycosyl allcncs. Kob&~, W. R.; Benozzi, C. R.; Bednarski, M. D. Tetrahedron Lett. 1992,33, 734.
1X. 19.
Rosen, T.; Lice, I. M.; Chu, D. T. W. J. Org. Chem. 1988,53,
1580.
Some other methods for the direct reductive acetylation of 2-azido sugars are described in: (a) Paulsen, H.; Adermann, K. Lie&
(Received
Ann. Chem.
1989, 751. (b) Ref lob.
in USA 19 February
1992)
(c) Ciommer, M.; Kunz, H, Synlert
1991, 593.