An efficient stereoselective synthesis of enantiomerically pure aziridine derivatives of allyl β-D-glucopyranosides asymmetrically induced by a glucide moiety

Article abstract of DOI:10.1016/S0957-4166(98)00427-3

The enantiomerically pure title aziridines were obtained by regioselective azidolysis of the 2',3'-epoxy derivatives of allyl 3,4,6-tri- O-benzyl-β-D-glucopyranosides, followed by cyclization of the corresponding azido alcohols by means of the PPh₃

Full text of DOI:10.1016/S0957-4166(98)00427-3

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 9 (1998) 4079–4088
An efficient stereoselective synthesis of enantiomerically pure
aziridine derivatives of allyl β-D-glucopyranosides
asymmetrically induced by a glucide moiety
Cinzia Chiappe,∗ Paolo Crotti, Elena Menichetti and Mauro Pineschi
Dipartimento di Chimica Bioorganica, Università di Pisa, via Bonanno 33, 56126 Pisa, Italy
Received 7 October 1998; accepted 20 October 1998
Abstract
The enantiomerically pure title aziridines were obtained by regioselective azidolysis of the 20,30-epoxy derivat-
ives of allyl 3,4,6-tri-O-benzyl-β-D-glucopyranosides, followed by cyclization of the corresponding azido alcohols
by means of the PPh3 protocol. Enantiomerically pure starting epoxides were prepared by epoxidation of the
corresponding allyl 3,4,6-tri-O-benzyl-β-D-glucopyranosidesasymmetrically induced by a glucide moiety. © 1998
Elsevier Science Ltd. All rights reserved.
1. Introduction
Chiral aziridines form an attractive class of organic compounds because they can be used for asymme-
tric synthesis in a number of different ways. The chemistry of aziridines is dominated by ring-opening
reactions, the driving force for which is relief of ring strain. By a suitable choice of substituents on the
carbon and nitrogen atoms, it is possible to obtain stereo- and regiocontrolled ring-opening reactions
with a wide variety of nucleophiles; this makes chiral aziridines useful as substrates for the preparation
of important bioactive molecules.1,2 In addition, it is noteworthy that a number of compounds possessing
an aziridine ring have been shown to exhibit potent biological activity, which is intimately associated
with the reactivity of the strained heterocycle.3,4
In the course of our research program studying the use of simple carbohydrates as efficient chiral
auxiliaries for asymmetric synthesis, we became interested in evaluating the effectiveness of the glucose-
derivative template in the preparation of chiral aziridine derivatives of allylic β-D-glucopyranosides,
which may not only have an intrinsic biological activity, but may also represent a source of optically
active β-hydroxy α-amino acids, and provide a convenient pathway to a variety of glycosphingolipids.
∗
Corresponding author. E-mail: cinziac@farm.unipi.it
0957-4166/98/$ - see front matter © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00427-3

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Natural glycosphingolipids are indeed an important class of organic compounds, mainly located in the
cell membrane, and frequently involved in immunological processes.5,6 However, only small amounts of
glycosphingolipids can be obtained from natural extracts,6 and consequently the development of efficient
synthetic methods for the preparation of these compounds has become one of the most timely problems
in synthetic chemistry and biochemistry.7
In this work, we report on the application of a general method for the preparation of aziridine
derivatives of allylic β-D-glucopyranosides, showing that the completely regioselective ring opening of
oxiranes, obtained in an enantiomerically pure form by epoxidation of the corresponding precursors
asymmetrically induced by a glucide moiety, represents a highly efficient procedure.
2. Results and discussion
Ring-opening of epoxides by azide ions followed by ring-closure of the resulting 1,2-azido alcohol
derivatives is a frequently applied route to aziridines, and when enantiomerically pure epoxides are used
in this reaction sequence, access to non-racemic aziridines is feasible.1 As it has been recently shown8,9
that oxidation of allyl β-D-glucopyranosides to the corresponding epoxides can be asymmetrically
induced by a glucide moiety, the following procedure was applied to obtain enantiomerically pure
aziridines derived from allyl β-D-glucopyranosides.
The appropriate allyl β-D-glucopyranosides used as starting materials in this synthetic approach were
prepared from the commercially available glucal 1, which was transformed into the corresponding
1,2-anhydro-3,4,6-tri-O-benzyl-α-D-glucose 2 by epoxidation following the MCPBA–KF protocol in
anhydrous CH2Cl2.10 The crude epoxide 2 (containing ca. 10% of the corresponding β-anomer)10 was
then subjected to oxirane ring-opening by treatment with the appropriate allyl alcohol in the presence of
ZnCl2 to give β-glycosides 3 (Scheme 1). Higher yields were obtained when the reactions were carried
out in THF at −78°C, in the presence of molecular sieves as a moisture scavenger, using the inverse
addition order of the reagents.8 The reaction mixtures were then purified by column chromatography
1
to give pure 3 (>80% yield, H NMR). C-Glycosides represent a field of noteworthy interest,11 and in
order to verify the possibility of applying the same procedure to obtain enantiomerically pure aziridine
derivatives of these compounds, the C-glycoside 4 was synthesized by treatment of the crude epoxide
mixture (2) with allyl magnesium bromide in the presence of a catalytic amount of CuBr·Me2S. The 1H
and 13C NMR spectra of 4, obtained in a satisfactory isolated yield (60%), turned out to be identical to
the previously reported data for this compound.12
The allyl glycosides 3a–d and the C-glycoside 4 were treated with anhydrified MCPBA in dichloro-
methane (Table 1), as previously reported,8 to give the corresponding epoxides 5, 6a–d and 7–8,
respectively (Scheme 2). The stereochemistry at the oxirane C-20 carbon of the glycidol moiety of the
main diastereoisomeric epoxides 5 arising from 3a and 3c had previously been established,8,9 whereas
that of epoxide 5b, arising from 3b, was tentatively attributed on the basis of the face enantioselection
observed in the reaction of 3a and 3c.8,9 It is noteworthy that, although the electrophilic attack of
the peracid occurs in 3a–c on the same face of the double bond of the allylic substituent, the 20(R)
stereochemistry of 5a and 5b becomes 20(S) in 5c because of the formal change in the descriptor caused
by the CIP priority rule.
In agreement with the previously observed high facial diastereoselection in the epoxidation of O-
glycosides 3a and 3c, the reaction of 3b gives pratically only one diastereoisomer (5b) (Table 1). How-
ever, when the same procedure was applied to the more reactive derivative 3d, a 1:1 mixture of the two
diastereoisomers, 5d and 6d, was obtained. Furthermore, in this case, even carrying out the epoxidation

C. Chiappe et al. / Tetrahedron: Asymmetry 9 (1998) 4079–4088
4081
Scheme 1.
Table 1
Epoxidation of 3a–d and 4 with MCPBA–KF protocol (1.2 equiv.)
Scheme 2.
at −80°C, the diastereoisomeric ratio remained extremely modest. Finally, no diastereoselection and a
very low reaction rate was found in the case of the C-glycoside 4 (Table 1).
As it has been shown8 that the stereoselectivity of epoxidation, as well as the reaction rate, largely
depend on the possibility of forming a hydrogen bond between the peracid and the OH substituent on the
C-2 carbon of the glucide moiety, the lack of diastereoface selection observed in the reaction of 4 may
be related to the absence of the anomeric oxygen in this compound. This structural feature, reducing the

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distance between the hydroxy group on C-2 and the double bond on the allyl substituent, makes the OH
group unable to direct the reaction. However, in the case of 3d, the low facial diastereoselection could be
attributed to the higher reactivity of the trisubstituted double bond, which makes the stabilization of the
transition state by the formation of a hydrogen bond between the reagent and the directing group on the
chiral inductor less important.
The 90:10 mixtures of the diastereoisomeric epoxides 5a–c and 6a–c were then subjected to oxirane
ring-opening with NaN3 in methanol:water in the presence of NH4Cl. In all cases the reaction occurred
in a completely regioselective way to give the diastereoisomeric azido alcohols 9a–c and 10a–c, arising
from the nucleophilic attack on C-30, in a practically quantitative yield (>90%), and in a 90:10 ratio
(Scheme 3).13
Scheme 3.
The subsequent transformation of the crude azido alcohol mixtures (9–10a–c) into the corresponding
aziridines was carried out with triphenylphosphine in acetonitrile. Besides triphenylphosphine oxide, the
two diastereoisomeric aziridines 11a–c and 12a–c were obtained in a ca. 90:10–95:5 ratio (Scheme 4). A
90:10 mixture of aziridines 11c and 12c was isolated, in an 80% yield, after column chromatography, and
characterized by 1H and 13C NMR spectra. In contrast, attempts to purify aziridines 11–12a and 11–12b
by column chromatography produced only decomposition products.
Scheme 4.
The stereochemistry at the aziridine carbon(s) of compounds 11a–c was finally established, taking into
account that the overall reaction sequence implies inversion at both atoms of the original epoxide. On the
basis of the absolute configuration of the starting epoxide, it is possible to assign the (S) configuration to
the C-20 carbon in compounds 11a and 11b, and the (20S,30R) configuration to the aziridine carbons of
11c.
Another well-established classic method to obtain aziridines is the reduction of haloazides prepared by
pseudo halogen addition to olefins.14 However, attempts to obtain diastereoisomerically pure aziridines,
11–12a–c, via iodo azides failed because of the very low, if any, face selection which characterizes the
IN3 addition reaction to the double bond of olefins 3b and 3c (Scheme 5).
Even at −78°C, the IN3 (generated in situ from ICl and NaN3) addition to glycosides 3b and 3c
carried out in anhydrous CH3CN, proceeded with a practically complete regioselection, to give the

C. Chiappe et al. / Tetrahedron: Asymmetry 9 (1998) 4079–4088
4083
Scheme 5.
products arising from addition of the nucleophile to the more substituted carbon,15 but without face
diastereoselection. In both cases, the corresponding compounds 13 and 14 were formed in a ca. 1:1 ratio.
In addition, when the reaction was carried out with the C-glycoside 4, the cyclic iodo ether 15, arising
from the intramolecular nucleophilic attack of the C-2 hydroxy group on the iodonium intermediate, was
obtained in a good yield and with a substantial appreciable diastereoisomeric purity (ca. 70%).
It is noteworthy that the same product 15 was also obtained in a practically diastereoisomerically
pure form when the reaction was carried out in dichloromethane under two phase conditions, using
tetrabutylammonium chloride for the ion transfer.16
Finally, aziridination attempts utilizing [N-(p-toluenesulphonyl)imino]phenylidinane (Ph=NTs) in the
presence of catalytic quantities of Cu(OTf)2 under ‘standard conditions’17 failed, giving the unreacted
starting material as the sole product.
In conclusion, these results show not only that the high diastereoselection obtained in the epoxidation
of allylic alcohols can easily be applied to the preparation of the corresponding aziridines, but also that
this method, among those generally used, is the only one able to give satisfactory results with these kinds
of compounds.
3. Experimental
All melting points were measured on a Kofler apparatus and are uncorrected. Optical rotations were
measured in CHCl3 solution (c=1.0ꢀ0.2) at 20ꢀ2°C with a Perkin–Elmer 241 polarimeter. NMR spectra
were registered with a Bruker AC 200 instrument using tetramethylsilane as the internal standard. All
reactions were followed by TLC Alugram® sil G/UV254 with detection by UV or with ethanolic 10%
sulphuric acid and heating. Kieselgel Macherey-Nagel (70–230 or 230–400 mesh) was used for column
and flash chromatography. Solvents were distilled and stored over 4 Å molecular sieves activated by
heating for 24 h at 400°C. Reactions in anhydrous conditions were carried out under an argon atmosphere.
MgSO4 was used as the drying agent for solutions. Anhydrous KF was obtained by heating at 120°C and
0.1 mmHg for 2 h.

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1,2-Anhydro-3,4,6-tri-O-benzyl-α-D-glucopyranose 2 was obtained as reported,8 and transformed into
the allyl 3,4,6-tri-O-benzyl-β-D-glucopyranosides 3a–d following the previously described procedure.8
3.1. 20-Methylpropenyl-3,4,6-tri-O-benzyl-β-D-glucopyranoside, 3b
[α]D −12.8 (c 3.6, CHCl3). 1H NMR (CDCl3) δ: 1.77 (s, 3H, CH3); 3.48–5.29 (m, 17H, allylic OCH2,
3 benzylic CH2, CH2_, H-6, H-60, H-5, H-4, H-3, H-2 and H-1); 7.13–7.37 (m, 15H aromatic H). 13C
NMR (CDCl3) δ: 20.11 (CH3); 69.32 (C6); 73.21 (allylic OCH2); 73.89, 75.39, 75.63 (benzylic CH2);
75.16, 75.55 (C-2 and C-5); 78.05 (C-4); 85.09 (C-3); 101.98 (C-1); 113.59 (CH2_); 128.10–128.85 (15
aromatic C); 138.63, 139.17 and 141.65 (3 quaternary aromatic C). Anal. calcd for C31H36O6: C, 73.79;
H, 7.19. Found: C, 73.56, H, 7.15.
3.2. trans-20-Butenyl-3,4,6-tri-O-benzyl-β-D-glucopyranoside, 3c
1
M.p. 43–45°C. [α]D 9.0 (c 2.1, CHCl3). H NMR (CDCl3) δ: 1.7 (d, 3H, J=6.0 Hz, CH3); 4.50 (m,
12H, allylic OCH2, 2 benzylic CH2, H-6, H-60, H-5, H-4, H-3 and H-2); 4.78–4.97 (m, 3H, benzylic
CH2 and H-1); 5.50–5.90 (m, 2H, CH_); 7.13–7.37 (m, 15 aromatic H). 13C NMR (CDCl3) δ: 17.80
(CH3); 68.85 (C-6); 70.07 (allylic OCH2); 73.43, 74.60, 74.96 (benzylic CH2); 75.09, 75.50 (C-2 and
C-5); 78.00 (C-4); 8.50 (C-3); 101.41 (C-1); 126.52 (CH_); 127.59–128.42 (15 CH); 130.73 (CH_);
138.01, 138.06, 138.57 (3 quaternary aromatic C). Anal. calcd for C31H36O6: C, 73.79, H, 7.19. Found:
C, 73.91, H, 6.99.
Compounds 3a and 3d were identified on the basis of the reported specific rotations and of 1H and 13
C
NMR spectra.8,18
3.3. C-Allyl 3,4,6-tri-O-benzyl-β-D-glucopyranoside, 4
1 M allyl magnesium bromide in Et2O (4.6 ml) was added to a solution of CuBr·Me2S (97 mg, 0.47
mmol) in 3 ml of THF, under an argon atmosphere at −30°C. At the end of the addition, compound 2
(1.30 g, 3.08 mmol) dissolved in THF (2 ml) was added. After 2 h of stirring at 0°C the resulting mixture
was poured into aqueous NH4Cl at 0°C, and extracted with CH2Cl2. The organic phase, washed and
dried, was evaporated in vacuo to give a residue (1.08 g), which was purified by column chromatography
over silica gel (7:3 hexane:AcOEt) to give pure 4 in a ca. 60% yield: m.p. 64–66°C [lit.12 63–65°C].
1
[α]D +36.6 (c 2.1, CHCl3) [lit.12 [α]D +37.5 (c 2.1, CHCl3)]. H NMR (CDCl3) δ: 3.3–3.1 (m, 8H,
allylic CH2, H-6, H-60, H-5, H-4, H-3, H-2); 4.5–5.2 (m, 9H, 3 benzylic CH2, CH2_, H-1); 5.9 (qt,
J=17, J=10 and J=7 Hz, CH_); 7.1–7.4 (m, 15 aromatic H). 13C NMR (CDCl3) δ: 36.05 (CH2CH_);
68.74 (C-6); 73.32, 74.65 and 75.05 (3 benzylic CH2); 78.29 and 78.64 (C-5 and C-4); 78.99 (C-3);
86.61 (C-1); 116.94 (CH2); 127.44–128.51 (15 aromatic CH); 134.50 (CH_); 137.93, 138.13, 138.48 (3
quaternary aromatic C).
3.4. 20,30-Epoxy derivatives of O-allyl and C-allyl 3,4,6-tri-O-benzyl-β-D-glucopyranosides, 5, 6a–d, 7
and 8
Allyl 3,4,6-tri-O-benzyl-β-D-glucopyranoside 3a–d (1 mmol) was added to a CH2Cl2 solution (5 ml)
of 70% MCPBA (1.2 mmol), previously dried for 20 min over Sikkon and MgSO4 and filtered. The
reaction mixture was left at the proper temperature for the time reported in Table 1, then diluted with
CH2Cl2, washed with an aqueous solution of NaHSO3 and NaHCO3, dried and evaporated in vacuo.

C. Chiappe et al. / Tetrahedron: Asymmetry 9 (1998) 4079–4088
4085
1
The residues were analyzed by H NMR in order to evaluate the conversion by the ratio between the
olefinic and oxirane protons, and the diastereoselectivity of the epoxidation, which was given by the
ratio between the signals for the diastereoisomeric oxirane H-30 protons. Yields and diastereoisomeric
ratios are reported in Table 1. The crude residues were purified by flash chromatography over silica gel
(hexane:AcOEt, 7:3, containing 0.1% Et3N) to obtain the starting glucoside 3 or 4 and a mixture of
the two diastereoisomeric epoxides. The mixture of epoxides 5 and 6, or 7 and 8, obtained always as
a syrup, showed: Mixture of 5a+6a: specific rotations and 1H and 13C NMR spectra in agreement with
those previously reported.8 Mixture of 5b+6b: [α]D −8.0 (c 1, CHCl3). 1H NMR (CDCl3) for 5b δ: 1.27
(s, 3H, CH3); 2.54 (d, 1H, J=4.8 Hz, H-30); 2.85 (d, 1H, J=4.8 Hz, H-30); 3.4–3.7 (m, 7H, H-6, H-60,
H-5, H-4, H-3, H-2, H-10); 3.90 (d, 1H, J=11.7 Hz, H-10); 4.5–5.0 (m, 7H, benzylic CH2 and H-1). 13
C
NMR (CDCl3) δ: 18.43 (CH); 51.15 (C-30); 56.10 (C-20); 68.74–71.14 (C-6 and C-10); 73.39, 74.86,
74.93 (benzylic CH2); 75.06 (C-2 and C-5); 77.22 (C-4); 84.51 (C-3); 103.59 (C-1); 127.59–128.31 (15
aromatic CH); 137.97, 137.97, 138.59 (3 quaternary aromatic C). The following signals were attributed to
6b: 13C NMR (CDCl3) δ: 102.59 (C-1); 51.7 (C-20). Anal. calcd for C31H36O7; C, 71.52, H, 6.97. Found:
C, 71.35, H, 6.93. Mixture of 5c+6c: [α]D −16 (c 3.0, CHCl3). 1H and 13C NMR spectra were identical
to those previously reported.9 Mixture of 5d+6d: 1H NMR (CDCl3) δ: 1.30 (d, 3H, J=8.7 Hz, CH3); 1.33
(d, 3H, J=8.8 Hz, CH3); 3.04 (m, 1H, C-20); 3.6–4.7 (m, 8H, allylic CH2, H-6, H-60, H-5, H-4, H-3, H-
2); 4.31 (m, 1H, H-1); 4.4–5.0 (m, 6H, benzylic CH2). 13C NMR (CDCl3) δ: 25.29 (CH3); 30.36 (CH3);
62.64 (C-20); 69.44–68.64 (C-6, C-10); 74.15, 75.10, 75.36 (benzylic CH2); 75.61 (C-2 and C-5); 78.34
(C-4); 85.10 (C-3); 103.57 (C-1); 128.0–129.0 (15 aromatic CH); 138.68, 138.68, 139.26 (3 quaternary
aromatic C). Although the spectra of the two diastereoisomeric epoxides were largely identical, it was
possible to distinguish the following signals: 13C NMR (CDCl3) δ: 62.00 (C-20) and 103.40 (C-1). Anal.
calcd for C32H38O7: C, 72.89, H, 7.16. Found: C, 71.75, H, 7.26. Mixture of 7+8: 1H NMR (CDCl3) δ:
2.85 (m, 2H, H-30); 3.1–3.8 (m, 9H, allylic CH2, H-6, H-60, H-5, H-4, H-3, H-2 and H-20); 4.97–4.70
(m, 7H, 3 benzylic CH2 and H-1); 7.12–7.40 (m, 15 aromatic H). 13C NMR (CDCl3) δ: 36.38 (C-10);
48.61 (C-30); 50.13 (C-20); 69.44 (C-6); 74.04, 75.45, 75.87 (benzylic CH2); 77.69 (C-2 and C-5); 78.88
(C-4); 79.32 (C-3); 87.22 (C-1); 117.70–129.30 (15 aromatic carbons). Although the spectra of the two
diastereoisomeric epoxides were largely identical, it was possible to distinguish the following signals:
13C NMR (CDCl3) δ: 35.18 (C-10); 47.40 (C-30); 49.94 (C-20); 79.05 (C-4); 79.57 (C-3); 87.32 (C-1).
Anal. calcd for C30H34O6: C, 73.45, H, 6.99. Found: C, 73.55, H, 6.95.
3.5. Oxirane ring-opening of mixtures of epoxides 5a–c+6a–c with NaN3 and transformation of azido
alcohols (9+10) into the corresponding aziridines (11+12)
Anhydrous NaN3 (4.5 equiv.) and NH4Cl (2.5 equiv.) were added to a MeOH:H2O (8:2) solution (2.5
ml) of the ca. 90:10 mixtures of epoxides 5a–c and 6a–c (1 equiv.) and the solution was stirred at 80°C.
The reactions were monitored by TLC and after 18–20 h, the mixtures were diluted with CH2Cl2, washed
with an aqueous solution of NaCl, and dried. Evaporation in vacuo of the solvent gave a residue (90–95%
yield) which was analyzed by 1H and 13C NMR.
3.5.1. 20-Hydroxy-30-azidopropyl-3,4,6-tri-O-benzyl-β-D-glucopyranosides, 9a–10a
[α]D −3.8 (c 1.8, CHCl3). 1H NMR (CDCl3) δ: 3.30–3.90 (m, 11H, H-6, H-60, H-5, H-4, H-2, H-3,
allylic OCH2, CHOH, CH2N3); 4.40–4.90 (m, 7H, 6H benzylic CH2, H-1); 7.10–7.40 (15 aromatic H).
13C NMR (CDCl3) δ: 53.09 (C-30, CH2N3); 68.56 (C-6); 69.86 (C-20, CHOH); 73.07 (C-10, CH2O);
74.15, 74.80, 74.91 (benzylic CH2); 77.42 (C-4); 84.33 (C-3); 103.35 (C-1); 127.0–133.0 (15 aromatic

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C. Chiappe et al. / Tetrahedron: Asymmetry 9 (1998) 4079–4088
CH); 137.70, 137.96, 138.33 (3 quaternary aromatic C); 74.21, 74.88 (C-2 and C-5). Only the anomeric
carbon was attributed to 10a: 13C NMR (CDCl3) δ: 103.55 (C-1).
3.5.2. 20-Hydroxy-20-methyl-30-azidopropyl-3,4,6-tri-O-benzyl-β-D-glucopyranosides, 9b–10b
[α]D −3.25 (c 2.1, CHCl3). 1H NMR (CDCl3) δ: 1.15 (s, 3H, CH3); 3.25 (AB system, 2H, J=12.3 Hz,
CH2N3); 3.4–4.0 (m, 8H, H-6, H-60, H-5, H-4, H-3, H-2, OCH2); 4.2–4.9 (m, 7H, CH2 benzylic, H-1);
7.10–7.40 (m, 15 aromatic H). 13C NMR (CDCl3) δ: 21.75 (CH3); 57.27 (CH2N3); 68.43 (C-6); 72.40
(quaternary COH); 73.31 (C-10); 74.77, 75.00, 75.40 (benzylic CH2); 73.99–74.85 (C-2 and C-5); 77.42
(C-4); 84.36 (C-3); 103.34 (C-1); 127.56–128.39 (15 aromatic C); 137.76, 137.76, 138.33 (3 quaternary
aromatic C). The following signals were attributed to 10b: 1H NMR (CDCl3) δ: 1.22 (d, 3H, CH3). 13
NMR (CDCl3) δ: 103.53 (C-1); 57.57 (CH2N3).
C
3.5.3. trans-20-Hydroxy-30-azidobutyl-3,4,6-tri-O-benzyl-β-D-glucopyranosides, 9c–10c
[α]D −7.8 (c 2.1, CHCl3). 1H NMR (CDCl3) δ: 1.28 (d, 3H, J=6.6 Hz, CH3); 3.40–3.95 (m, 10H, H-6,
H-60, H-5, H-4, H-3, H-2, OCH2, CHOH, CHN3); 4.3–5.0 (m, 7H, benzylic CH2 and H-1); 7.10–7.40
(15 aromatic H). 13C NMR (CDCl3) δ: 15.14 (CH3); 58.43 (CHN3); 68.59 (C-6); 72.60 (C-10); 73.20
(CHOH); 73.41, 74.88, 75.18 (benzylic CH2); 74.08–74.88 (C-2 and C-5); 77.44 (C-4); 84.32 (C-3);
103.27 (C-1); 127.83–133.48 (15 aromatic CH); 137.72, 137.72, 138.34 (3 quaternary aromatic C). The
following signals were attributed to 10c: 1H NMR (CDCl3) δ: 1.22 (d, 3H, CH3). 13C NMR (CDCl3) δ:
103.53 (C-1).
PPh3 (1 equiv.) was added to the crude azido alcohols (9+10a–c) dissolved in CH3CN (2 ml) and
the mixture was kept at room temperature with stirring until the evolution of N2 was observed (ca. 30
min) and then refluxed for ca. 16 h. After cooling, the solvent was removed in vacuo and the residue,
1
consisting of a mixture of aziridines 11+12 and triphenylphosphine oxide was analyzed by H and
13C NMR. Purification by column chromatography over silica gel (4:4:2 hexane:CH2Cl2:Et3N) made
it possible to obtain, only in the case of 11c and 12c, a pure fraction containing the two corresponding
diastereoisomeric aziridines in a 90:10 ratio. Attempts to purify aziridines 11a+12a and 11b+12b by
column chromatography failed because of the products’ instability. 11c and 12c (90:10 ratio): [α]D +2.0
(c 2.1, CHCl3). 1H NMR (CDCl3) δ: 1.19 (d, 3H, J=5.4 Hz, CH3); 1.92 [m, 2H, CH(NH)–CH]; 3.3–3.7
(m, 9H, H-6, H-60, H-5, H-4, H-3, H-2, allylic CH2, OH, NH); 4.1 (dd, 1H, J=11.3 and 3.2 Hz, OCH2);
4.27 (d, 1H, J=6.9 Hz, OCH2); 4.5–5.1 (m, 6H, benzylic CH2). 13C NMR (CDCl3) δ: 18.38 (C-40, CH3);
29.75 (C-30, CHN); 37.00 (CHN); 68.77 (C-6); 69.57 (OCH2); 73.24, 74.75, 74.78 (benzylic CH2);
74.78, 73.89 (C-2 and C-5); 77.26 (C-4); 84.65 (C-3); 102.90 (C-1); 127.00–132.00 (15 aromatic C);
138.00, 138.00, 138.73 (3 quaternary aromatic C). The following signals were attributed to 12c: 13C
NMR (CDCl3) δ: 103.90 (C-1); 69.38 (OCH2); 36.60, 29.37 (CHN). Anal. calcd for C31H37O6N: C,
71.65; H, 7.18; N, 2.70. Found: C, 71.53; H, 7.25; N, 2.55.
3.6. Iodine azide addition reaction to 3b–c and 4. General procedure
3.6.1. In acetonitrile
ICl (1.12 mmol), previously dissolved in CH3CN (2 ml), was added to a stirred slurry of NaN3 (2.5
mmol) in CH3CN (2 ml) cooled at −78°C. The reaction mixture was stirred for 10 min and then, after
the addition of the glycoside (1 mmol), allowed to warm to room temperature. At the end of the reaction,
which in all cases was followed by TLC, the reaction mixture was diluted with CH2Cl2 and washed with
aqueous NaHSO3. The organic phase was dried and evaporated in vacuo to give a residue (90% yield),
which was analyzed by 1H and 13C NMR.

C. Chiappe et al. / Tetrahedron: Asymmetry 9 (1998) 4079–4088
4087
3.6.2. From 3b: 30-iodo-20-methyl-20-azidopropyl-3,4,5-tri-O-benzyl-β-D-glucopyranoside (13b+14b)
1H NMR (CDCl3) δ: 1.39 (s, 3H, CH3); 1.44 (s, 3H, CH); (m, 10H, OCH2, H-60, H-6, H-5, H-3, H-2,
CH2I); 4.50–5.00 (m, 7H, 3 benzylic CH2 and H-1); 7.20–7.50 (m, 15 aromatic H). 13C NMR (CDCl3)
δ: 12.40 (CH2I); 22.55 (CH3); 62.50 (CN3); 69.28 (C-6); 74.72 (OCH2); 74.10, 75.83, 75.83 (benzylic
CH2); 75.62 (C-2 and C-5); 77.93 (C-4), 84.99 (C-3); 103.67 (C-1); 127.00–132.00 (15 aromatic C);
138.00, 138.00, 138.73 (3 quaternary C). Although the spectra of the two diastereoisomeric iodo azido
derivatives were largely identical, it was possible to distinguish the following signals: 13C NMR (CDCl3)
δ: 12.16 (CH2I); 22.13 (CH3); 62.15 (CN3). On the basis of the intensity of these signals a 60:40 ratio
between the two diastereoisomeric products was evaluated.
3.6.3. From 3c: 30-iodo-20-azidobutyl-3,4,6-tri-O-benzyl-β-D-glucopyranoside or 20-iodo-30-azido-
butyl-3,4,6-tri-O-benzyl-β-D-glucopyranoside (13c+14c)
1H NMR (CDCl3) δ: 1.60 (d, 3H, CH3); 3.40–4.40 (m, 10H, OCH2, H-60, H-6, H-5, H-3, H-2, CHI,
CHN3); 4.50–5.00 (m, 7H, 3 benzylic CH2 and H-1); 7.20–7.50 (m, 15 aromatic H). 13C NMR (CDCl3)
δ: 24.42 (CH3); 38.87 (CHI); 56.94 (CHN3); 68.50 (C-6); 72.58 (CH2O); 73.42, 74.46, 74.95 (benzylic
CH2); 75.01 (C-2 and C-5); 77.19 (C-4); 84.25 (C-3); 102.66 (C-1); 127.00–132.00 (15 aromatic C);
138.00, 138.00, 138.73 (3 quaternary C). Although the spectra of the two diastereoisomeric iodo azido
derivatives were largely identical, it was possible to distinguish the following signals: 13C NMR (CDCl3)
24.58 (CH3); 39.72 (CHI); 57.25 (CN3); 103.24 (C-1). On the basis of the intensity of these signals a
50:50 ratio between the two diastereoisomeric products was evaluated.
3.6.4. From 4: compound 15 (85:15 mixture of the two diastereoisomers)
1H NMR (CDCl3) δ: 1.70–2.20 (m, 2H, CH2); 2.50 (m, 1H, CH); 3.10–3.70 (m, 8H, CH2, H-6, H-
60, H-5, H-4, H-3, H-2); 4.30–5.00 (m, 7H, 3 benzylic CH2 and H-1); 7.20–7.50 (m, 15 aromatic H).
13C NMR (CDCl3) δ: 10.15 (CH2I); 35.66 (CH2); 72.87, 73.35, 75.25 (benzylic CH2); 68.94 (C-6);
77.25 (C-2); 78.0 (C-5); 78.38 (C-4); 80.49 (C-3); 81.92 (CH); 84.07 (C-1); 127.00–132.00 (15 aromatic
C); 138.00, 138.00, 138.73 (3 quaternary C). Although the spectra of the two diastereoisomers were
largely identical, it was possible to distinguish the following signals: 13C NMR (CDCl3) δ: 83.70 (C-1);
34.08 (CH2); 11.28 (CH2I). On the basis of the intensity of these signals an 85:15 ratio between the two
diastereoisomeric products was evaluated. [Lit.12: 13C NMR of the major isomer δ: 11.2 (t); 34.3 (t);
73.0 (t), 73.5 (t), 75.3 (t); 69.3 (t); 77.5 (d); 77.6 (d); 78.0 (d); 80.9 (d); 83.8 (d); 83.9 (d).]
3.7. In dichloromethane
ICl (1.5 mmol) was added to a stirred slurry of NaN3 (3 mmol) in anhydrous CH2Cl2 (4 ml), containing
tetrabutylammonium chloride (0.03 mmol). After 2 h at room temperature, the mixture was cooled at
−78°C and 4 (1 mmol) was added with stirring. The reaction mixture was stirred for another 4 h and then
allowed to warm to room temperature. After 1 h at room temperature the reaction mixture was washed
with aqueous NaHSO3, dried and evaporated in vacuo to give 15 (90% yield; ≥98% d.r.), which was
analyzed by 1H and 13C NMR.

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C. Chiappe et al. / Tetrahedron: Asymmetry 9 (1998) 4079–4088
Acknowledgements
This work was supported in part by grants from the Consiglio Nazionale delle Ricerche (CNR, Roma)
and the Ministero dell’Università e della Ricerca Scientifica e Tecnologica (MURST, Roma), and by
MERCK 1998 ADP Chemistry.
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