N-Nosyl as a stereoselectivity-improving and easily removable group in the O-glycosylation of d-allal and d-galactal-derived allyl aziridines. Stereospecific synthesis of 4-amino-2,3-unsaturated-O-glycosides

Article abstract of DOI:10.1016/j.tet.2006.12.069

The glycosylation of alcohols, phenol, and partially protected monosaccharides with the diastereoisomeric d-allal and d-galactal-derived N-nosyl aziridines 2α and 2β leads to the corresponding 4-N-(nosylamino)-2,3-unsaturated-α-O- (6α) and β-O-glycosides

Full text of DOI:10.1016/j.tet.2006.12.069

Tetrahedron 63 (2007) 2482–2489
N-Nosyl as a stereoselectivity-improving and easily removable
group in the O-glycosylation of D-allal and D-galactal-derived
allyl aziridines. Stereospecific synthesis of 4-amino-2,3-
unsaturated-O-glycosides
*
Valeria Di Bussolo, Maria Rosaria Romano, Mauro Pineschi and Paolo Crotti
Dipartimento di Chimica Bioorganica e Biofarmacia, Universitaꢀ di Pisa, Via Bonanno 33, 56126 Pisa, Italy
Received 4 October 2006; revised 12 December 2006; accepted 21 December 2006
Available online 28 December 2006
Abstract—The glycosylation of alcohols, phenol, and partially protected monosaccharides with the diastereoisomeric D-allal and D-galactal-
derived N-nosyl aziridines 2a and 2b leads to the corresponding 4-N-(nosylamino)-2,3-unsaturated-a-O- (6a) and b-O-glycosides and
disaccharides (6b), respectively, in a stereospecific substrate-dependent O-glycosylation process. The N-(nosylamino) group of 6a and
6b can easily be deprotected to give the corresponding 4-amino-2,3-unsaturated-O-glycosides 7a and 7b, with an increased value to our
glycosylation protocol.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
proved not to be sufficiently reactive,3 our choice fell on
aziridines 2a and 2b, which bear the N-(o-nitrobenzenesul-
fonyl) [N-(nosyl)] protecting/activating group, which is eas-
ily removable by the PhSH/K2CO3 protocol, in accordance
with a SNAr reaction mechanism.4 Application of this proto-
col to the –NH-nosyl group present in compounds 6a and
6b, which derive from the glycosylation process, would
give the corresponding free –NH2-containing products 7a
and 7b, as desired (Scheme 1).
Mono- and oligosaccharides bearing a free amino group
(amino sugars) are an important class of sugars, widely
present in nature, with important biological properties.1
Consequently, the realization of effective procedures for
the stereo- and regioselective introduction of an amino func-
tionality on a glycosidic structure may be valuable.
We recently found that the D-allal- 1a and D-galactal-derived
N-mesyl allyl aziridine 1b can be successfully used for the
completely regio- and highly, or even completely, stereo-
selective glycosylation with O-nucleophiles (alcohols, par-
tially protected monosaccharides, and phenol) to afford the
corresponding a-O-glycosides 5a from 1a and b-O-glyco-
sides 5b from 1b (Scheme 1).2 As a consequence of the
conjugate addition involved in this glycosylation process, a
N-mesylamino group, having the same configuration of the
starting aziridine, is regioselectively delivered to the C(4)
of the newly formed pseudoglycal system present in 5a
and 5b. As the N-mesylamino group is not actually the
best choice to have a free amino group by deprotection pro-
cedures, it appeared necessary to introduce on the starting
aziridine a different N-activating group, which could easily
be removed after the glycosylation process had taken place.
Considering that the simple N-acetyl group could not be
used because the corresponding N-acetyl aziridine had
OR3
O
O
O
R3OH
BnO
R2O
base
BnO
BnO
R1HN
N
NHR1
R1
t-BuOK
R1= R2= Ms
1
5
3
4
benzene
K2CO3
PhSH
7 , R1=H
R1=Ns; R2= Ms
2
6
K2CO3
MeCN
OR3
O
O
O
R3OH BnO
BnO
R2O
base
BnO
R1HN
N
NHR1
R1
t-BuOK
benzene
K2CO3
MeCN
R1= R2= Ms
3
4
5
1
2
PhSH
R1=Ns; R2= Ms
7 , R1=H
6
K2CO3
R3OH = alcohols, partially protected monosaccharides and phenol
(ref.2 and Tables 1 and 2)
Keywords: Allyl aziridines; Glycals; Glycosylation; Amino sugars.
* Corresponding author. Tel.: +39 050 2219 690; fax: +39 050 2219 660;
e-mail: crotti@farm.unipi.it
Scheme 1.
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.12.069

V. Di Bussolo et al. / Tetrahedron 63 (2007) 2482–2489
2483
2. Results
MeCN, instead of the t-BuOK (1 equiv)/benzene protocol,
which has been routinely used with the corresponding N-
mesyl analogues 3a and 3b.2
As the N-nosyl aziridines 2a and 2b are not stable, it was
first necessary to prepare their stable precursors, the corre-
sponding N-nosyl-O-mesylate 4a and 4b. The reaction of
the diastereoisomeric trans amino alcohols 9a and 9b, ob-
tained from epoxides 8b2a and 8a,2b respectively, with nosyl
chloride (NsCl) (1 equiv) afforded the corresponding N-
nosyl derivatives 10a and 10b, which were treated with
MsCl (2 equiv) in CH2Cl2/pyridine to give 4a and 4b, re-
spectively. Following a previously reported protocol,5 the
cyclization of 4a and 4b to the corresponding N-nosyl azir-
idines 2a and 2b was carried out with K2CO3 (3 equiv) in
To check the efficiency of aziridines 2a and 2b as glycosyl
donors, the possible influence of the N-nosyl group on the
regio- and stereoselectivity, and the applicability of the
deprotection procedure on the N-(nosylamino)-substituted
compounds (6a and 6b) deriving from the glycosylation
process, we examined the regio- and stereochemical behav-
ior of aziridines 2a and 2b in the reaction with alcohols,
partially protected monosaccharides, and phenol (O-nucleo-
philes) (Scheme 2).
NsCl
MsCl
O
O
O
O
O
BnO
BnO
BnO
BnO
BnO
HO
(1 equiv)
(2 equiv)
K2CO3
MeCN
Py
53%
CH2Cl2/Py
63%
HO
MsO
N
O
NHNs
10
NHNs
4
Ns
Ns
NH2
9
2
8
NsCl
MsCl
O
O
O
O
O
K2CO3
MeCN
BnO
BnO
BnO
BnO
BnO
HO
(1 equiv)
(2 equiv)
Py
80%
Py
65%
HO
MsO
N
O
NHNs
10
NHNs
4
NH2
9
8
2
Scheme 2.
Table 1. Regio- and stereoselectivity of the addition reaction of O-nucleophiles to N-nosyl aziridine 2a under protocols A and Ba
-glycoside
-glycoside
11, R=Me
12, R=Et
O
O
O
OR
13, R= i-Pr
14, R= t-Bu
15, R= allyl
16, R= Bn
O
OR
BnO
BnO
MsO
BnO
BnO
NsHN
ROH
K2CO3
MeCN
+
NsHN
N
NHNs
Ns
17, see entry 10
18, see entry 11
2
11 -18
11 -18
4
Entry
1
Glycosyl acceptor (ROH)
MeOH
Protocol
A
Time (h)
3
Product(s)
Yield (%)
95b
11a (60%)
11b (40%)
11a (>99%)
12a (73%)
12b (27%)
2
3
MeOH
EtOH
B
A
3
3
68c
89b
4
5
6
7
8
9
EtOH
i-PrOH
i-PrOH
t-BuOH
CH2]CHCH2OH
PhCH2OH
B
A
B
A
B
B
3
3
3
3
3
3
12a (>99%)
13a (>99%)
13a (>99%)
14a (>99%)
15a (>99%)
16a (>99%)
80c
98b
65c
92b
63c
63c
Me
Me
Me
Me
HO
O
O
BnO
10
B
B
3
3
66c
NsHN
Me
(+)-Menthol
HO
Me
17a (>99%)
O
O
BnO
O
O
O
O
O
O
NsHN
11
60c
O
O
O
O
18a (>99%)
1,2;3,5-Di-O-isopropylidene-a-D-glucofuranose
a
Protocol A: ROH, as the solvent; protocol B: MeCN, as the solvent, ROH¼2–3 equiv.
Crude product.
Purified product (flash chromatography or preparative TLC).
b
c

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V. Di Bussolo et al. / Tetrahedron 63 (2007) 2482–2489
Table 2. Regio- and stereoselectivity of the addition reaction of O-nucleophiles to N-nosyl aziridine 2b under protocols A and Ba
-glycoside
-glycoside
19, R=Me
20, R=Et
O
OR
O
O
OR
O
BnO
BnO
BnO
NsHN
BnO
MsO
ROH
K2CO3
MeCN
21, R= i-Pr
22, R= t-Bu
23, R= allyl
24, see entry 10
25, R= Ph
+
NsHN
N
Ns
NHNs
2
19 -25
Time (h)
19 -25
4
Entry
1
Glycosyl acceptor (ROH)
MeOH
Protocol
A
Product(s)
Yield (%)
87b
3
19a (75%)
19b (25%)
19b (>99%)
20a (65%)
20b (35%)
20b (>99%)
21a (40%)
21b (60%)
21b (>99%)
22b (>99%)
23b (>99%)
2
3
MeOH
EtOH
B
A
3
3
63c
98b
4
5
EtOH
i-PrOH
B
A
3
3
71c
98b
6
7
8
i-PrOH
t-BuOH
CH2]CHCH2OH
B
B
B
3
3
3
65c
70c
75c
O
O
O
O
O
O
O
9
B
3
67c
O
O
O
O
BnO
O
HO
NsHN
24b (>99%)
25b (>99%)
Diacetone-D-glucose
PhOH
10
B
3
80c
a
Protocol A: ROH, as the solvent; protocol B: MeCN, as the solvent, ROH¼2–3 equiv.
Crude product.
Purified product (flash chromatography or preparative TLC).
b
c
Two conceptually different protocols were used. When pos-
1a and a-anomer from aziridine 1b) were detected in many
cases.2 With the present N-nosyl-substituted aziridines 2a
and 2b, complete stereoselectivity is obtained with all the
O-nucleophiles used and the corresponding a-anomer from
2a and b-anomer from 2b are the only reaction products,
in the stereospecific O-glycosylation process (Tables 1 and
2). It is significant in this respect to compare the results
obtained from the reactions with MeOH and PhOH. In the
reaction with MeOH, the N-mesyl aziridine 1b afforded
a 85:15 mixture of the corresponding methyl b-26b and a-
glycoside 26a (Scheme 3; Table 3 entry 2),2b whereas in
the reaction with PhOH a 15:45:40 mixture of all the possi-
ble addition products (a-1,4-adduct 27a, b-1,4-adduct 27b,
and anti 1,2-adduct 28) was unexpectedly obtained (Scheme
3; Table 3 entry 9).2b The same reactions repeated with
the corresponding N-nosyl aziridine 2b gave a completely
regio- and stereoselective result in both the cases affording
the methyl b-glycoside 19b (reaction with MeOH) and the
phenyl b-glycoside 25b (reaction with PhOH), as the only
respective reaction product (Table 2 entries 2 and 11, or
Table 3 entries 6 and 10).
sible: (a) a solution of the aziridine precursor, the N-nosyl-O-
mesylate 4a or 4b in the alcohol (O-nucleophile) was treated
with K2CO3 (3 equiv) (protocol A); (b) the base, K2CO3
(3 equiv), was added to an MeCN solution of 4a or 4b,
containing the O-nucleophile (3 equiv) (protocol B). Under
protocol A, the reaction of the in situ-formed aziridine oc-
curred in the presence of a very large amount of nucleophile,
whereas under protocol B, the nucleophile was present only
to a very reduced extent. As glycosyl acceptors, MeOH,
EtOH, i-PrOH, and t-BuOH, were used for both protocols
A and B, whereas allyl alcohol, benzyl alcohol, (+)-menthol,
diacetone-D-glucose, 1,2;3,5-diisopropyliden-a-D-gluco-
furanose, and phenol were used only for protocol B. The
results obtained are shown in Tables 1 and 2.
3. Discussion
The results obtained indicate that the regio- (only the 1,4-
adduct was observed) and stereoselectivity (a-1,4-adduct/
b-1,4-adduct ratio) of N-nosyl aziridines 2a and 2b under
protocol A closely resembles those previously obtained
with the corresponding N-mesyl aziridines 1a and 1b, re-
spectively.2 On the contrary, a substantial difference is found
under protocol B between aziridines 1a and 1b and 2a and
2b. With aziridines 1a and 1b, the reactions were not com-
pletely stereoselective in all cases and some amounts, up to
15%, of the anomer with an inverted configuration with re-
spect to the aziridine ring carbons (b-anomer from aziridine
The complete 1,4-regioselectivity and aziridine ring config-
uration-related stereoselectivity, observed in all the reactions
of the N-nosyl aziridines 2a and 2b with O-nucleophiles,
can be rationalized, as previously admitted for 1a and 1b,
by the occurrence of an effective coordination (hydrogen
bond) of the O-nucleophile with the aziridine nitrogen of
2a and 2b, followed by a nucleophilic attack on the nearby
C(1) of the allyl aziridine system (routes a and b for 2a and

V. Di Bussolo et al. / Tetrahedron 63 (2007) 2482–2489
2485
O
O
O
OR
O
OR
BnO
BnO
BnO
BnO
MsHN
ROH
3
+
+
t-BuOK
MsHN
MsHN
benzene
N
OPh
Ms
R = Me
R = Ph
26
27
26
27
28
1
Scheme 3.
Table 3. Regio- and stereoselectivity of the addition of MeOH and PhOH to N-mesyl aziridine 1b and N-nosyl aziridine 2b
Entry
Aziridine
Generating base
and solvent
Glycosyl acceptor
Protocola
Time (h)
Product(s)
Yield (%)
1
2
1b
1b
t-BuOK/MeOH
t-BuOK/benzene
MeOH
MeOH
A
B
2
2
26a (69%)
26b (31%)
26a (15%)
26b (85%)
26b (>99%)
26a (22%)
26b (78%)
19a (75%)
19b (25%)
19b (>99%)
19b (>99%)
19a (10%)
19b (90%)
27a (15%)
27b (45%)
28 (40%)
92b,c
92b,c
3
4
1b
1b
K2CO3/MeCN
t-BuOK/benzene 18-crown-6
MeOH
MeOH
B
B
2
2
97c
97b,c
5
2b
K2CO3/MeOH
MeOH
A
3
87c
6
7
8
2b
2b
2b
K2CO3/MeCN
t-BuOK/benzene
t-BuOK/benzene 18-crown-6
MeOH
MeOH
MeOH
B
B
B
3
18
18
63c
86d
86d
9
1b
t-BuOK/benzene
PhOHa
B
3
90b,c
10
11
12
2b
2b
1b
K2CO3/MeCN
t-BuOK/benzene
K2CO3/MeCN
PhOH
PhOH
PhOH
B
B
B
3
1.5
3
25b (>99%)
25b (>99%)
27b (>99%)
80d
96c
89c
a
See Tables 1 and 2.
Ref. 2b.
Crude product.
b
c
d
Purified product (flash chromatography or preparative TLC).
2b, respectively, Scheme 4).2 Additionally, in the present
case, the metal ion (K+) probably plays a role in determining
the complete stereoselectivity observed (vide infra).
comparison with entry 2, Table 3) unequivocally points to
the importance of the metal cation (K+) on the stereoselectiv-
ity, on the other hand, the complete b-stereoselectivity ob-
tained with N-nosyl aziridine 2b (entry 7 and comparison
with entry 2, Table 3) tends to indicate that the nature of
the arylsulfonyl group is also important. This point is con-
firmed also by the reactions of aziridines 1b and 2b, both
generated by t-BuOK/benzene protocol, carried out in the
presence of 18-crown-6, the crown ether specific for K+:
the N-nosyl aziridine 2b affords a better b-stereoselective re-
sult than the N-mesyl derivative 1b (Table 3 entries 4 and 8).
Similar considerations may be made as regards the results
obtained in the reaction with PhOH under different condi-
tions. Particularly significant is the complete 1,4-regio-
and b-stereoselectivity obtained with N-nosyl aziridine 2b,
when generated by the t-BuOK/benzene cyclization protocol
(Table 3 entry 11); in the same conditions, the N-mesyl azir-
idine 1b had previously given a non-regioselective (forma-
tion of both 1,2- and 1,4-adduct) and a non-stereoselective
result (formation of both a- and b-anomer) (Table 3 entry
9).2b At the same time, the N-mesyl aziridine 1b, when
In this framework, the higher stereoselectivity observed with
the N-nosyl aziridines 2a and 2b than with the N-mesyl azir-
idines 1a and 1b could be due to either an intrinsically
higher ability to coordinate with the aziridine nitrogen of
the N-nosyl group than in the mesyl case and/or to the coor-
dinating–chelating ability of K+, which is present in a decid-
edly large amount (6 equiv) in the reaction mixture in which
aziridines 2a and 2b are prepared by the K2CO3/MeCN cy-
clization protocol on the N-nosyl-O-mesylates 4a and 4b,
respectively (see above). In order to clarify this point, appro-
priate experiments were carried out on aziridines 1b and 2b,
generated in situ by inverted procedures (1b by K2CO3/
MeCN cyclization of 3b and 2b by t-BuOK/benzene cycli-
zation of 4b), in their reaction with MeOH and PhOH under
protocol B (Table 3). While, on the one side, the complete
b-stereoselectivity observed under these conditions in the
reaction of N-mesyl aziridine 1b with MeOH (entry 3 and
-
+
Ns
R
OBn
O
H
O
O
OR
N
O
OR
BnO
NsHN
OBn
O
BnO
NsHN
route b
route a
1
a
+
N
b
1
Ns
H
O
-1,4-adduct
-1,4-adduct
2 '
2 '
R
Scheme 4.

2486
V. Di Bussolo et al. / Tetrahedron 63 (2007) 2482–2489
OR
OR
OR
O
O
OR
O
O
BnO
H2N
BnO
BnO
NsHN
BnO
PhSH
K2CO3/MeCN
PhSH
K2CO3/MeCN
NsHN
11-13, 16,17
R= see Tables 1 and 2
H2N
29-33
22-24
34-36
Scheme 5.
generated by the K2CO3/MeCN-promoted cyclization proto-
col, behaves like the N-nosyl aziridine 2b, affording a com-
pletely regio- and stereoselective result (Table 3 entry 12).
corresponding 4-amino-2,3-unsaturated-O-glycosides 7a
and 7b, bearing a free amino group in the same position,
with an added value to the final product and to the glycosyl-
ation process itself. The obtained results indicate that the use
of our O-glycosylation process by means of the N-nosyl azir-
idines 2a and 2b, followed by the deprotection protocol,
may constitute a simple and valid tool for the stereospecific
synthesis of 2,3-unsaturated-4-amino sugars.
The 4-N-(nosylamino)-O-glycosides 11–13a, 16a, 17a, and
22–24b were chosen in order to check the applicability of
these pseudoglycals to the deprotection procedure, which
makes use of the PhSH/K2CO3 protocol.4 In this way, a solu-
tion of the methyl 4-N-(nosylamino)-a-O-glycoside 11a
(R¼Me), taken as an example, in MeCN was treated with
PhSH (3 equiv) in the presence of K2CO3 (4 equiv) (solution
phase conditions): the deprotection reaction is very fast and
5. Experimental
5.1. General
1
is completed in 3 h (conversion>99%, TLC and H NMR)
and the corresponding methyl 4-amino-a-O-glycoside 29a
(R¼Me) is obtained in pure form (65% yield) after simple
preparative TLC or flash chromatography (Scheme 5). How-
ever, with the aim of eliminating the purification step, an al-
ternative procedure (solid phase conditions) was tested, by
treating a THF solution of glycoside 11a (R¼Me) with a
PhSH-supported resin (PS-thiophenol).6 Unfortunately,
under these conditions, the deprotection process turned out
to be very slow and after several days and/or addition (2–3
times) of an equal amount of fresh resin, the conversion to
29a (R¼Me) was not complete and a substantial amount
(20%) of the starting glycoside 11a was still present. As
a consequence, preparative TLC or flash chromatography
was still necessary in order to obtain the pure free amino
derivative 29a (R¼Me). Comparison of the two procedures
indicated that the solution phase conditions were to be pre-
ferred and, consequently, they were adopted in all the other
cases [4-N-(nosylamino)-O-glycosides 12a, 13a, 16a, 17a,
and 22–24b, Scheme 5]. Under these simple conditions, the
corresponding 4-amino-O-glycosides 30–33a and 34–36b
were obtained pure, rapidly (3 h at room temperature), and
in good yields (55–75%) (Scheme 5).
All reactions were performed in flame-dried modified
Schlenk (Kjeldahl shape) flasks fitted with a glass stopper or
rubber septa under a positive pressure of argon. Air and/or
moisture-sensitive liquids and solutions were transferred via
syringe. Flash column chromatography was performed with
230–400 mesh silica gel (Macherey–Nagel). Analytical TLC
was performed on Alugram SIL G/UV254 silica gel sheets
(Macherey–Nagel) with detection by 0.5% phosphomolyb-
dic acid solution in 95% EtOH. MeOH, i-PrOH, t-BuOH,
BnOH, and allylic alcohol were distilled from calcium
hydride. EtOH (absolute), phenol, (+)-menthol, 1,2;5,6-di-
O-isopropylidene-a-D-glucofuranose (diacetone-D-glucose),
and anhydrous MeCN over molecular sieves were purchased
from Aldrich and used without purification. 1,2;3,5-di-
O-isopropylidene-a-D-glucofuranose was prepared as re-
ported.7 PS-thiophenol resin was purchased from Stepbio.
Epoxides 8a8a and 8b8b and trans amino alcohol 9a2a and
9b2b were prepared as previously described. In the reaction
carried out under protocol A, a solution of trans N-nosyl-O-
mesylates 4a and 4b in anhydrous MeCN was treated with
K2CO3 in the presence of the glycosyl acceptor (MeOH,
EtOH, i-PrOH, t-BuOH, phenol, allylic alcohol, BnOH,
(+)-menthol, 1,2;5,6-di-O-isopropylidene-a-D-glucofura-
nose (diacetone-D-glucose), 1,2;3,5-di-O-isopropylidene-a-
D-glucofuranose (3 equiv). In the reaction carried out under
protocol B, trans N-nosyl-O-mesylates 4a and 4b were
treated with K2CO3 in the glycosyl acceptor (MeOH,
EtOH, i-PrOH, t-BuOH), as the solvent.
4. Conclusion
In conclusion, our original glycosylation protocol of alco-
hols, partially protected monosaccharides, and phenol by
the diastereoisomeric D-allal and D-galactal-derived allyl
N-mesyl aziridines 1a and 1b has now been substantially
improved by the use of the corresponding N-nosyl aziridines
2a and 2b.2 On passing from the N-mesyl to the N-nosyl
protecting/activating group, the stereoselectivity of all the
O-glycosylation reactions increases, to the point that the
addition reactions of the new N-nosyl-aziridines 2a and 2b
are completely stereoselective, affording the corresponding
4-N-(nosylamino)-2,3-unsaturated-a- (6a) and b-O-glyco-
sides (6b), respectively, in a new uncatalyzed substrate-
dependent stereospecific glycosylation process. The
N-(nosylamino) functionality, regio- and stereoselectively
introduced at C(4) of 6a and 6b, can be easily deprotected
by the simple PhSH/K2CO3 protocol to give the
5.1.1. 6-O-Benzyl-3-deoxy-3-N-(nosylamino)-D-gulal
(10a).
A solution of amino alcohol 9a (0.117 g,
0.50 mmol) in anhydrous CH2Cl2 (1.7 mL) was treated at
room temperature with Et3N (0.076 mL, 0.55 mmol) and
NsCl (0.121 g, 0.55 mmol) and the reaction mixture was
stirred 2 h at the same temperature. Dilution with CH2Cl2
(30 mL) and evaporation of the washed (saturated aqueous
NaHCO3, 1ꢀ5 mL, and saturated aqueous NaCl, 1ꢀ5 mL)
organic solution afforded a crude residue (0.214 g) consist-
ing of the N-nosyl derivative 10a, which was subjected to
flash chromatography. Elution with an 1:1 hexane/AcOEt
mixture yielded the N-nosylate 10a (0.108 g, 53% yield),

V. Di Bussolo et al. / Tetrahedron 63 (2007) 2482–2489
2487
pure as a yellow liquid, [a]2D0 +25.2 (c 1.04, CHCl3):
Rf¼0.19 (1:1 hexane/AcOEt); FTIR (neat film) n 3479,
the treatment of a solution of the N-nosyl derivative 10b
(0.63 g, 1.50 mmol) in anhydrous CH2Cl2 (8 mL) with anhy-
drous pyridine (0.36 mL, 4.5 mmol) and MsCl (0.23 mL,
3.0 mmol) afforded, after 18 h stirring at 0 ꢂC, a crude residue
(1.05 g) consisting of the trans N-nosyl-O-mesyl derivative
4b, which was subjected to flash chromatography. Elution
with a 4:3:3 hexane/CH2Cl2/AcOEt mixtureyielded the trans
N-nosyl-O-mesylate 4b (0.38 g, 51% yield), as a pale yellow
solid, mp 39–41 ꢂC; [a]D20 ꢁ54.5 (c 0.52, CHCl3): Rf¼0.32
(1:1 hexane/AcOEt); FTIR (Nujol) n 3310, 1653, 1541,
1
3350, 1650, 1540, 1450, 1360, 1240, 1150, 1020 cmꢁ1. H
NMR (CDCl3) d 8.10–8.18 (m, 1H), 7.82–7.90 (m, 1H),
7.65–7.80 (m, 2H), 7.24–7.43 (m, 5H), 7.00 (d, 1H, J¼
7.5 Hz), 5.35–5.42 (m, 1H, NH), 4.62 (d, 1H, J¼12.0 Hz),
4.52 (d, 1H, J¼12.0 Hz), 4.36 (t, 1H, J¼3.7 Hz), 3.84–
3.92 (m, 1H), 3.74 (unresolved d, 2H, J¼3.7 Hz), 3.56–
3.81 (m, 2H), 3.18 (br s, 1H, OH). 13C NMR (CDCl3)
d 150.0, 133.6, 133.0, 131.0, 128.7, 128.3, 128.0, 125.6,
92.5, 77.4, 74.2, 69.8, 64.4, 51.2. Anal. Calcd for
C19H20N2O7S: C, 54.28; H, 4.79; N, 6.66. Found: C,
54.03; H, 4.65; N, 6.56.
1
1466, 1351 cmꢁ1. H NMR (CDCl3) d 8.11–8.21 (m, 1H),
7.85–7.94 (m, 1H), 7.71–7.83 (m, 2H), 7.21–7.45 (m, 5H),
6.33 (dd, 1H, J¼6.0, 1.7 Hz), 5.88 (d, 1H, J¼8.9 Hz, NH),
4.97 (dd, 1H, J¼7.9, 6.8 Hz), 4.66 (d, 1H, J¼11.7 Hz), 4.55
(d, 1H, J¼11.7 Hz), 4.12–4.41 (m, 3H), 3.84 (dd, 1H,
J¼11.5, 3.1 Hz), 3.77 (dd, 1H, J¼11.5, 4.0 Hz), 3.21 (s,
3H). 13C NMR (CDCl3) d 146.3, 137.4, 134.3, 134.2,
133.4, 130.9, 128.6, 128.2, 128.0, 125.7, 97.9, 76.1, 75.6,
73.8, 68.1, 51.9, 39.6. Anal. Calcd for C20H22N2O9S2: C,
48.19; H, 4.45; N, 5.62. Found: C, 47.98; H, 4.39; N, 5.56.
5.1.2. 6-O-Benzyl-3-deoxy-3-N-(nosylamino)-D-glucal
(10b). Following the above described procedure, the
treatment of a solution of amino alcohol 9b (0.310 g,
1.32 mmol) in anhydrous CH2Cl2 (4.6 mL) with Et3N
(0.2 mL, 1.45 mmol) and NsCl (0.322 g, 1.45 mmol) af-
forded, after 3 h stirring at room temperature, a crude residue
(0.560 g) consisting of the N-nosyl derivative 10b, which
was subjected to flash chromatography. Elution with an
1:1 hexane/AcOEt mixture yielded the N-nosylate 10b
(0.448 g, 80% yield), pure as a yellow liquid, [a]2D0 +3.8 (c
1.07, CHCl3): Rf¼0.29 (1:1 hexane/AcOEt); FTIR (neat
film) n 3344, 1650, 1540, 1380, 1230, 1180, 1160, 1100,
5.1.5. Glycosylation of alcohols, partially protected
monosaccharides, and phenol in anhydrous MeCN by
the in situ-formed allyl aziridines 2a and 2b (protocol B).
5.1.5.1. Reaction of aziridine 2a with MeOH in anhy-
drous MeCN. Typical procedure (protocol B): a solution
of trans N-nosyl-O-mesylate 4a (0.032 g, 0.064 mmol)
in anhydrous MeCN (3.6 mL) was treated with K2CO3
(0.026 g, 0.192 mmol, 3 equiv) in the presence of MeOH
(0.008 mL, 0.192 mmol, 3 equiv) and the reaction mixture
was stirred at room temperature for 3 h. The solution was
partitioned between Et2O (15 mL) and brine (5 mL), and
the aqueous layer was further extracted with Et2O
(2ꢀ10 mL). Evaporation of the combined organic extracts
afforded a clean crude product (0.027 g, 97% yield) consist-
ing of practically pure methyl glycoside 11a (1H NMR),
which was subjected to flash chromatography. Elution
with an 1:1 hexane/AcOEt mixture afforded pure methyl
6-O-(benzyl)-2,3,4-trideoxy-4-N-(nosylamino)-a-D-erythro-
hex-2-enopyranoside (11a) (0.019 g, 68% yield), as a yellow
liquid, [a]2D0 +104.2 (c 0.80, CHCl3): Rf¼0.30 (1:1 hexane/
AcOEt); FTIR (neat film) n 3329, 1732, 1541, 1456, 1363,
1050, 1020 cmꢁ1 1H NMR (CDCl3) d 8.17 (dd, 1H,
.
J¼5.8, 3.5 Hz), 7.91 (dd, 1H, J¼6.0, 3.4 Hz), 7.70–7.82
(m, 2H), 7.25–7.40 (m, 5H), 6.35 (dd, 1H, J¼5.9, 1.9 Hz),
5.51 (d, 1H, J¼7.6 Hz, NH), 4.64 (d, 1H, J¼12.1 Hz),
4.55 (d, 1H, J¼12.1 Hz), 4.41 (dd, 1H, J¼5.9, 2.1 Hz), 3.95–
4.10 (m, 1H), 3.74–3.93 (m, 4H), 2.90 (br s, 1H, OH).
13C NMR (CDCl3) d 146.1, 137.6, 134.4, 133.8, 133.1,
131.4, 128.7, 127.8, 125.5, 99.2, 77.6, 73.9, 69.4, 69.1,
55.4. Anal. Calcd for C19H20N2O7S: C, 54.28; H, 4.79; N,
6.66. Found: C, 54.35; H, 4.82; N, 6.74.
5.1.3. 6-O-Benzyl-3-deoxy-3-N-(nosylamino)-4-O-mesyl-
D-gulal (4a). A solution of the N-nosyl derivative 10a
(2.13 g,5.07 mmol)inanhydrousCH2Cl2 (27 mL)wastreated
at 0 ꢂC with anhydrous pyridine (1.22 mL, 15.21 mmol) and
MsCl (0.78 mL, 10.14 mmol) and the reaction mixture was
stirred 18 h at 0 ꢂC. Dilution with CH2Cl2 (200 mL) and
evaporation of the washed (water, 2ꢀ15 mL) organic solution
afforded a crude residue (2.9 g) consisting of trans N-nosyl-O-
mesyl derivative 4a, which was subjected to flash chromato-
graphy. Elution with a 4:3:3 hexane/CH2Cl2/AcOEt mixture
yielded the trans N-nosyl-O-mesylate 4a (1.26 g, 50% yield),
pure as a pale yellow solid, mp 102–105 ꢂC; [a]D20 +89.3 (c
0.61, CHCl3): Rf¼0.33 (1:1 hexane/AcOEt); FTIR (Nujol)
1288, 1170, 1072 cmꢁ1 1H NMR (CDCl3) d 8.06–8.16
.
(m, 1H), 7.80–7.89 (m, 1H), 7.72 (td, 1H, J¼7.5, 1.8 Hz),
7.65 (td, 1H, J¼7.5, 1.8 Hz), 7.23–7.40 (m, 5H), 5.75 (dt,
1H, J¼10.1, 2.6 Hz), 5.51 (d, 1H, J¼10.1 Hz), 5.39 (d,
1H, J¼9.4 Hz, NH), 4.85–4.93 (m, 1H, H-1), 4.52 (s, 2H),
4.24–4.40 (m, 1H), 3.81–3.92 (m, 1H), 3.65–3.80 (m, 2H),
3.42 (s, 3H). 13C NMR (CDCl3) d 147.9, 138.2, 134.4,
133.9, 133.1, 131.0, 130.1, 128.3, 128.2, 127.9, 127.7,
125.6, 95.2, 73.7, 69.4, 68.8, 56.1, 48.9. Anal. Calcd for
C20H22N2O7S: C, 55.29; H, 5.10; N, 6.45. Found: C,
55.35; H, 5.24; N, 6.51.
n 3319, 1647, 1543, 1371, 1251, 1178 cmꢁ1 1H NMR
.
(CDCl3) d 8.22–8.31 (m, 1H), 7.61–7.92 (m, 3H), 7.23–7.43
(m, 5H), 6.57 (d, 1H, J¼5.9 Hz), 5.39 (d, 1H, J¼4.9 Hz,
NH), 4.96–5.03 (m, 1H), 4.63 (td, 1H, J¼5.9, 1.7 Hz), 4.52
(s, 2H), 4.22 (t, 1H, J¼6.8 Hz), 3.96–4.05 (m, 1H), 3.74 (dd,
1H, J¼9.8, 6.0 Hz), 3.64 (dd, 1H, J¼9.8, 7.5 Hz), 3.03 (s,
3H). 13C NMR (CDCl3) d 148.2, 137.4, 134.3, 133.4, 132.2,
128.7, 128.3, 125.7, 95.5, 73.9, 73.8, 70.0, 67.4, 47.7, 37.9.
Anal. Calcd for C20H22N2O9S2: C, 48.19; H, 4.45; N, 5.62.
Found: C, 48.31; H, 4.49; N, 5.70.
5.1.5.2. Reaction of aziridine 2a with 1,2;3,5-di-O-iso-
propylidene-a-D-glucofuranose in anhydrous MeCN
(protocol B). Following the above described typical proce-
dure, the treatment of a solution of trans N-nosyl-O-mesyl-
ate 4a (0.035 g, 0.070 mmol) in anhydrous MeCN (4 mL)
with K2CO3 (0.029 g, 0.210 mmol, 3 equiv) in the presence
of 1,2;3,5-di-O-isopropylidene-a-D-glucofuranose (0.036 g,
0.140 mmol, 2 equiv) afforded, after 3 h stirring at room
temperature, a crude product consisting of a mixture of
5.1.4. 6-O-Benzyl-3-deoxy-3-N-(nosylamino)-4-O-mesyl-
D-glucal (4b). Following the above described procedure,

2488
V. Di Bussolo et al. / Tetrahedron 63 (2007) 2482–2489
disaccharide 18a and unreacted monosaccharide (1H NMR),
which was subjected to flash chromatography. Elution with
a 9:1 CH2Cl2/AcOEt mixture afforded 3-O-[6-O-benzyl-
2,3,4-trideoxy-4-N-(nosylamino)-a-D-erythro-hex-2-eno-
pyranosyl]-1,2;3,5-di-O-isopropylidene-a-D-glucofuranose
(18a) (0.028 g, 60% yield), as a yellow liquid, [a]2D0 +95.9
(c 1.58, CHCl3): Rf¼0.29 (7:3 hexane/acetone); FTIR (neat
film) n 3290, 1732, 1541, 1456, 1373, 1242, 1168, 1076,
Rf¼0.16 (7:3 hexane/acetone); FTIR (neat film) n 3358,
1
1541, 1413, 1261, 1070 cmꢁ1. H NMR (CDCl3) d 8.09–
8.16 (m, 1H), 7.79–7.87 (m, 1H), 7.69 (td, 1H, J¼7.4,
2.0 Hz), 7.62 (td, 1H, J¼8.6, 3.0 Hz), 7.23–7.41 (m, 5H),
5.84–5.95 (m, 3H), 5.71 (d, 1H, J¼10.2 Hz), 5.32 (d, 1H,
J¼1.3 Hz, H-1), 4.61 (d, 1H, J¼3.8 Hz), 4.41 (s, 2H),
4.25–4.35 (m, 2H), 4.19 (dd, 1H, J¼6.8, 3.3 Hz), 3.89–4.11
(m, 4H), 3.61 (d, 2H, J¼5.9 Hz), 1.50 (s, 3H), 1.39 (s, 3H),
1.34 (s, 3H), 1.32 (s, 3H). 13C NMR (CDCl3) d 148.0,
137.9, 133.6, 132.9, 130.5, 130.4, 130.3, 128.6, 128.0,
127.8, 125.5, 112.2, 109.1, 105.3, 96.2, 83.8, 80.5, 77.8,
73.7, 73.6, 72.8, 69.3, 67.0, 48.3, 27.1, 27.0, 26.5, 25.5.
Anal. Calcd for C31H38N2O12S: C, 56.18; H, 5.78; N, 4.23.
Found: C, 56.27; H, 5.91; N, 4.31.
1026 cmꢁ1
.
1H NMR (CDCl3) d 8.09 (dd, 1H, J¼7.2,
2.0 Hz), 7.84 (dd, 1H, J¼7.5, 1.6 Hz), 7.70 (td, 1H, J¼7.4,
1.7 Hz), 7.63 (td, 1H, J¼7.4, 1.6 Hz), 7.23–7.40 (m, 5H),
5.97 (d, 1H, J¼3.7 Hz), 5.76 (dt, 1H, J¼10.1, 2.6 Hz),
5.52 (d, 1H, J¼10.1 Hz), 5.34 (d, 1H, J¼9.2 Hz, NH),
5.04 (br s, 1H, H-1), 4.56 (d, 1H, J¼3.7 Hz), 4.49 (s, 2H),
4.26–4.43 (m, 2H), 4.18 (d, 1H, J¼3.8 Hz), 3.73–3.96 (m,
4H), 3.69 (unresolved d, 2H, J¼2.9 Hz), 1.48 (s, 3H), 1.33
(s, 9H). 13C NMR (CDCl3) d 147.9, 138.2, 134.5, 133.9,
133.2, 131.1, 130.1, 128.5, 128.3, 127.9, 127.7, 125.6,
112.3, 106.5, 101.0, 92.2, 84.1, 79.6, 75.1, 73.7, 71.4,
69.4, 68.8, 68.6, 48.7, 27.4, 26.7, 24.2. Anal. Calcd for
C31H38N2O12S: C, 56.18; H, 5.78; N, 4.23. Found: C,
56.35; H, 5.85; N, 4.41.
5.1.6. Glycosylation of alcohols by the in situ-formed allyl
aziridines 2a and 2b, in alcohol as the solvent/nucleo-
phile (protocol A).
5.1.6.1. Reaction of aziridine 2a with MeOH as the
solvent/nucleophile. Typical procedure (protocol A): a solu-
tion of trans N-nosyl-O-mesylate 4a (0.040 g, 0.080 mmol)
in anhydrous MeOH (4.4 mL) was treated with K2CO3
(0.033 g, 0.240 mmol, 3 equiv) and the reaction mixture
was stirred at room temperature for 2 h. The solution was
partitioned between Et2O (15 mL) and brine (5 mL), and
the aqueous layer was further extracted with Et2O
(2ꢀ10 mL). Evaporation of the combined washed (brine) or-
ganic extracts afforded a crude reaction product (0.033 g,
95% yield) consisting of a 60:40 mixture of methyl glyco-
sides 11a and 11b (1H NMR), which was subjected to pre-
parative TLC using a 6:4 CH2Cl2/i-Pr2O mixture, as the
eluant (3 runs). Extraction of the two most intense bands
(the faster moving band contained 11b) afforded pure 11a
(0.016 g, 46% yield) and methyl 6-O-benzyl-2,3,4-tri-
deoxy-4-N-(nosylamino)-b-D-erythro-hex-2-enopyranoside
(11b) (0.011 g, 31% yield), as a yellow liquid, [a]2D0 +24.1 (c
0.98, CHCl3); FTIR (neat film) n 3325, 1537, 1452, 1417,
5.1.5.3. Reaction of aziridine 2b with MeOH in anhy-
drous MeCN (protocol B). Following the above described
typical procedure, the treatment of a solution of trans N-
nosyl-O-mesylate 4b (0.031 g, 0.062 mmol) in anhydrous
MeCN (3.5 mL) with K2CO3 (0.026 g, 0.186 mmol,
3 equiv) in the presence of MeOH (0.008 mL, 0.186 mmol,
3 equiv) afforded, after 3 h stirring at room temperature,
a crude product (0.024 g, 90% yield) consisting of practi-
cally pure methyl glycoside 19b (1H NMR), which was sub-
jected to flash chromatography. Elution with an 1:1 hexane/
AcOEt mixture afforded pure methyl 6-O-(benzyl)-2,3,4-
trideoxy-4-N-(nosylamino)-b-D-threo-hex-2-enopyranoside
(19b) (0.017 g, 63% yield), as a yellow liquid, [a]2D0 ꢁ136.7
(c 0.90, CHCl3): Rf¼0.28 (1:1 hexane/AcOEt); FTIR (neat
film) n 3354, 1541, 1456, 1417, 1396, 1168, 1120,
1
1357, 1261, 1167, 1080 cmꢁ1. H NMR (CDCl3) d 8.05
1
1053 cmꢁ1. H NMR (CDCl3) d 8.09–8.16 (m, 1H), 7.81–
(dd, 1H, J¼7.8, 1.3 Hz), 7.84 (dd, 1H, J¼7.9, 1.2 Hz),
7.68 (td, 1H, J¼7.7, 1.4 Hz), 7.49 (td, 1H, J¼7.7, 1.3 Hz),
7.24–7.42 (m, 5H), 5.82 (d, 1H, J¼11.0 Hz), 5.72 (dd, 1H,
J¼11.0, 3.8 Hz), 5.58 (d, 1H, J¼9.3 Hz, NH), 4.88–4.93
(m, 1H, H-1), 4.47 (s, 2H), 4.04–4.19 (m, 1H), 3.63–3.88
(m, 2H), 3.57 (dd, 1H, J¼9.9, 5.1 Hz), 3.41 (s, 3H). 13C
NMR (CDCl3) d 148.0, 138.3, 134.7, 133.8, 133.1, 131.3,
129.5, 128.6, 127.9, 126.9, 125.5, 95.6, 75.1, 73.5, 69.9,
55.6, 48.1. Anal. Calcd for C20H22N2O7S: C, 55.29; H,
5.1; N, 6.45. Found: C, 55.12; H, 5.36; N, 6.32.
7.88 (m, 1H), 7.60–7.76 (m, 2H), 7.24–7.39 (m, 5H), 5.73
(s, 2H), 5.71 (d, 1H, J¼7.7 Hz, NH), 5.00 (d, 1H,
J¼1.7 Hz, H-1), 4.45 (s, 2H), 3.88–4.09 (m, 2H), 3.68 (dd,
1H, J¼10.1, 5.6 Hz), 3.62 (dd, 1H, J¼10.1, 6.3 Hz), 3.47
(s, 3H). 13C NMR (CDCl3) d 147.9, 138.1, 135.4, 133.7,
133.1, 131.0, 130.5, 128.9, 128.6, 127.9, 125.5, 98.4, 73.6,
73.5, 69.7, 55.6, 48.7. Anal. Calcd for C20H22N2O7S: C,
55.29; H, 5.10; N, 6.45. Found: C, 55.17; H, 4.89; N, 6.32.
5.1.5.4. Reaction of aziridine 2b with 1,2;5,6-di-O-iso-
propylidene-a-D-glucofuranose (diacetone-D-glucose) in
anhydrous MeCN (protocol B). Following the above
described typical procedure, the treatment of a solution
of N-nosyl-O-mesylate 4b (0.028 g, 0.056 mmol) in anhy-
drous MeCN (3.2 mL) with K2CO3 (0.023 g, 0.168 mmol,
3 equiv) in the presence of diacetone-D-glucose (0.029 g,
0.112 mmol, 2 equiv) afforded, after 3 h stirring at room tem-
perature, a crude product consisting of a mixture of disaccha-
ride 24b and unreacted monosaccharide (1H NMR), which
was subjected to flash chromatography. Elution with a 7:3
hexane/acetone mixture afforded 3-O-[6-O-benzyl-2,3,4-tri-
deoxy-4-N-(nosylamino)-b-D-threo-hex-2-enopyranosyl]-1,
2;5,6-di-O-isopropylidene-a-D-glucofuranose(24b) (0.025 g,
67% yield), as a yellow liquid, [a]2D0 ꢁ33.6 (c 0.33, CHCl3):
5.1.6.2. Reaction of aziridine 2b with MeOH as the
solvent/nucleophile (protocol A). Following the above
described typical procedure, the treatment of a solution
of trans N-nosyl-O-mesylate 4b (0.033 g, 0.066 mmol) in
anhydrous MeOH (3.7 mL) with K2CO3 (0.027 g,
0.198 mmol, 3 equiv) afforded, after 2 h stirring at room
temperature a crude product (0.025 g, 87% yield) consisting
of a 75:25 mixture of methyl glycosides 19a and 19b (1H
NMR), which proved to be inseparable under any chromato-
graphic conditions.
5.1.7. Deprotection of 4-N-nosyl-O-glycoside 11a by
the PhSH/K2CO3 protocol. Typical procedure: a solution
of 4-N-nosyl-O-glycoside 11a (0.016 g, 0.037 mmol) in

V. Di Bussolo et al. / Tetrahedron 63 (2007) 2482–2489
2489
anhydrous MeCN (0.9 mL) was treated with K2CO3
(0.020 g, 0.148 mmol, 4 equiv) in the presence of PhSH
(0.011 mL, 0.111 mmol, 3 equiv) and the resulting reaction
mixture was stirred 3 h at room temperature. The solution
was diluted with AcOEt (20 mL). The organic solution
was filtered through a short Celite pad and evaporated to
afford a crude product consisting of a mixture of 4-amino-
O-glycoside 29a and PhSH (1H NMR), which was subjec-
ted to preparative TLC using an 1:1:0.1 CH2Cl2/AcOEt/
MeOH mixture, as the eluant. Extraction of the slower
moving band afforded methyl 6-O-(benzyl)-2,3,4-trideoxy-
4-amino-a-D-erythro-hex-2-enopyranoside (29a) (0.006 g,
65% yield), as a yellow liquid, [a]2D0 +46.2 (c 0.49,
CHCl3): Rf¼0.12 (1:1:0.1 CH2Cl2/AcOEt/MeOH); FTIR
(neat film) n 3360, 3296, 1454, 1396, 1261, 1097,
In other runs, even if operating under the same experimental
conditions, the starting 4-N-nosyl-O-glycoside 11a was re-
covered completely unreacted.
Acknowledgements
ꢀ
This work was supported by the Universita di Pisa and
MIUR (Ministero dell’Istruzione, della Universita e della
ꢀ
Ricerca) Roma. P.C. gratefully acknowledges Merck
Research Laboratories for the generous financial support
deriving from the 2005 ADP Chemistry Award.
Supplementary data
1
1057 cmꢁ1. H NMR (CDCl3) d 7.27–7.41 (m, 5H), 5.88
(d, 1H, J¼10.1 Hz), 5.74 (dt, 1H, J¼10.1, 2.4 Hz), 4.87–
4.93 (m, 1H, H-1), 4.69 (d, 1H, J¼12.2 Hz), 4.55 (d, 1H,
J¼12.2 Hz), 3.71–3.77 (m, 2H), 3.54–3.66 (m, 1H), 3.38–
3.52 (m, 1H), 3.44 (s, 3H), 1.36–1.56 (m, 2H, NH2). 13C
NMR (CDCl3) d 135.4, 128.6, 127.9, 125.5, 95.4, 73.6,
72.8, 70.3, 55.8, 47.1. Anal. Calcd for C14H19NO3: C,
67.45; H, 7.68; N, 5.62. Found: C, 67.61; H, 7.78; N, 5.34.
Supplementary data associated with this article can be found
in the online version, at doi:10.1016/j.tet.2006.12.069.
References and notes
1. (a) Banoub, J.; Boullanger, P.; Lafont, D. Chem. Rev. 1992, 92,
ꢁ
1167–1195; (b) van den Bos, L. J.; Codee, J. D. C.; van Boom,
5.1.8. Deprotection of 4-N-nosyl-O-glycoside 11a by the
PS-thiophenol resin protocol.6 A solution of 4-N-nosyl-
O-glycoside 11a (0.030 g, 0.070 mmol) in anhydrous THF
(0.2 mL) was treated with Cs2CO3 (0.072 g, 0.22 mmol)
and PS-thiophenol resin (0.040 g, 0.08 mmol). This amount
of resin had been previously treated by shaking for 30 min in
a sealed vial with 1.6 mL of a 0.7 M solution of PPh3 in
anhydrous deoxygenated THF. The resin was filtered on a
sintered glass, washed with anhydrous THF (30 mL), and
used immediately without drying. The reaction mixture
was shaken in a sealed vial at room temperature for 8 h. Addi-
tional PS-thiophenol resin was added (0.040 g, 0.08 mmol)
and the reaction mixture was shaken again for 16 h. The re-
action mixture was filtered and the solid was washed several
times with CH2Cl2 (20 mL). Evaporation of the combined
organic extracts afforded a crude product consisting of an
80:20 mixture of 4-amino-O-glycoside 29a and unreacted
4-N-nosyl-O-glycoside 11a (1H NMR), which was sub-
jected to preparative TLC using an 1:1 hexane/AcOEt mix-
ture, as the eluant. Extraction of the two most intense bands
(the slower moving band contained 29a) afforded pure 29a
(0.012 g, 70% yield) and 11a (0.004 g, 15% yield).
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