Glycosylations with 2,3-aziridinofuranose derivatives

Article abstract of DOI:10.1016/j.tet.2013.03.074

Two aziridine-containing pentofuranose derivatives were synthesized from d-arabinose and their ability to glycosylate alcohols was explored. The major products are those in which the newly formed glycosidic bond is cis to the aziridine moiety, although in

Full text of DOI:10.1016/j.tet.2013.03.074

Tetrahedron 69 (2013) 4276e4284
Contents lists available at SciVerse ScienceDirect
Tetrahedron
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Glycosylations with 2,3-aziridinofuranose derivatives
*
Md Faiaz Ahmed, Todd L. Lowary
Alberta Glycomics Centre and Department of Chemistry, The University of Alberta, Gunning-Lemieux Chemistry Centre, Edmonton, Alberta,
T6G 2G2 Canada
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 January 2013
Received in revised form 13 March 2013
Accepted 19 March 2013
Available online 29 March 2013
Two aziridine-containing pentofuranose derivatives were synthesized from D-arabinose and their ability
to glycosylate alcohols was explored. The major products are those in which the newly formed glycosidic
bond is cis to the aziridine moiety, although in all cases the stereoselectivity is modest. The analogous
epoxides have been shown to be more highly stereoselective glycosyl donors. Differences in glycosylation
stereoselectivity between the epoxide and aziridine-containing substrates was proposed to arise from
steric hindrance between the alcohol acceptor and the nitrogen protecting group in the aziridine
substrates.
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
use of such species as glycosyl donors. If these species are highly
stereoselective glycosylating agents, then they may find application
Previously, we have reported the use of 2,3-anhydrosugar
derivatives (e.g., 1e3, Fig. 1) as donors for the synthesis of glyco-
side bonds.1e4 These species are highly stereoselective glycosyl
donors, producing the product in which the newly formed bond is
cis to the epoxide ring. The products can be further functionalized
through regioselective epoxide ring opening to produce
in the synthesis of furanose aminosugars through subsequent nu-
cleophilic opening of the aziridine ring.
2. Results and discussion
In developing a route to 4 and 5, we envisioned an approach
glycans containing
b a
-arabinofuranoside,2 -arabinofuranoside5 or
(Fig. 2) starting from -arabinose (6) and proceeding through a key
D
a
-galactofuranoside3 moieties. Thioglycosides, such as 1 and 3 are
azidosugar intermediate (7), which possesses a leaving group at C-
2. In our earlier studies on 2,3-anhydrosugar donors, we had
employed thioglycoside donors, and corresponding sulfoxides
also effective precursors for the stereocontrolled synthesis of
2-deoxy-glycosides.6,7
STol
BzO
STol
BzO
S(O)Tol
O
BzO
O
O
O
O
OR
BzO
BzO
N
Ac
O
O
1
2
3
4, R = H
5, R = C(=NH)CCl3
Fig. 1. 2,3-Anhydrosugar glycosyl donors 1e3 and related aziridine derivatives 4 and 5.
In this paper, we report an extension of these investigations and
explore the ability of 4 and 5, analogs of 2 in which the epoxide
moiety is replaced with an aziridine, to glycosylate alcohols. To the
best of our knowledge, there have been no previous reports on the
derived from them.1e5 However, based on this work, we expected
that use of a thioglycoside (X¼SR) in this approach would likely
lead to decomposition of 7 via displacement of the C-2 leaving
group by neighboring group participation of the sulfur atom, gen-
erating oxacarbenium ion 8.8 We therefore chose to prepare donors
(i.e., 4 and 5) containing an oxygen at C-1. Should 4 and 5 prove to
be highly stereoselective glycosyl donors, an alternate route to
targets containing a thioglycoside moiety could be developed.
* Corresponding author. E-mail addresses: tlowary@ualberta.ca, carbres@ual-
berta.ca (T.L. Lowary).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.03.074

M.F. Ahmed, T.L. Lowary / Tetrahedron 69 (2013) 4276e4284
4277
4 & 5
BzO
OLG
X
X = OR
X = SR
OH
OH
BzO
O
O
O
OH
8
HO
N3
6
7
N3
X
LG = Leaving Group
Fig. 2. General strategy to 4 and 5 and predicted decomposition pathway with thioglycosides.
2.1. Synthesis of 4 and 5
the aziridine moiety is cis to the allyl group and trans to the ben-
zoyloxymethyl group.y
The synthesis of 4 (Scheme 1) began with allyl
a
-
D
-arabinofur-
The unit cell of the crystal contains two molecules of 13. The
furanose ring in both molecules adopts similar conformations with
pseudorational phase angle (P) and puckering amplitude (fm) values
of 266ꢁ/28.5ꢁ and 277ꢁ/20.5ꢁ, respectively.14,15 Interestingly, the
relative orientation of the acetyl group differs in the two molecules
(Fig. 3b). In one, the acetyl group is positioned away from, and in the
other it is oriented under, the furanose ring. These forms appear to
represent the two different ‘inverted’ forms of the nitrogen. It is
anoside (9), which is easily available from
D
-arabinose (6).9 Re-
action of 9 with diisopropyl azodicarboxylate, triphenylphosphine,
and benzoic acid provided 10 in 82% yield.10 The formation of 2,3-
epoxide moiety was clear from the chemical shift of signals for C-
2 and C-3 in the 13C NMR spectrum, which appeared at 56.3 and
54.1 ppm, respectively. These values are similar to those reported
for other 2,3-anhydro-
a-
D
-lyxofuranosides.11
OH
BzO
HO
O
O
O
BzOH, DIAD, Ph3P, THF
82%
NaN3, NH4Cl, EtOH,
O
O
H2O
HO
10
9
90%
1. Ph3P, H2O, THF
2. Et3N, DMF
3. Ac2O, pyridine
OH
OTs
BzO
BzO
O
O
TsCl, pyridine
79%
79%
O
O
N3
N3
12
11
1. H2, [Ir(COD)(PMePh2)2]PF6, THF
2. OsO4, TMANO, CH2Cl2
BzO
O
Cl3CCN, DBU, CH2Cl2
98%
4
5
O
N
Ac
98%
13
Scheme 1. Synthesis of 4 and 5.
Opening of the epoxide ring in 10 was performed using NaN3
and NH4Cl in EtOH and H2O. The reaction was sluggish and it was
necessary to heat the mixture at reflux for 48 h. The product,11, was
obtained in 90% yield, together with 9% recovered starting material
10. A peak at 2107 cmꢀ1 in the IR spectrum of 11 confirmed the
presence of the azido group. The regioselectivity of the reaction was
confirmed by the 13C NMR spectrum of 11. The resonance for C-2
appeared at 80.9 ppm for C-2 and that for C-3, as expected, at lower
known that aziridine N-acylation reduces the barrier to nitrogen
inversion;16 in 13 it appears that both forms are energetically similar,
at least in the solid state. To date, only 23 crystal structures of N-
acylated aziridines have been deposited in the Cambridge Crystal-
lographic Database17e37 and in only four of those cases20,24,27,28 does
the until cell contain more than one molecule. In all four of these, the
relative position of the acyl group in the different molecules is the
same. Thus, 13 appears to be the first N-acylated aziridine in which
both inverted nitrogen forms are populated in the crystal.
3
chemical shift, 67.5 ppm. In addition, the JH-1,H2 (1.0 Hz) was
consistent with a product possessing the arabinofuranose stereo-
chemistry.12 The regioselectivity observed in the epoxide opening
was expected based on previous work on the nucleophilic opening
of 2,3-anhydrofuranosides.2,13 Reaction of 11 with tosyl chloride in
pyridine afforded 12. Subsequently, the reduction of the azide using
the Staudinger reaction, followed by treatment with triethylamine
and finally acetylation (Ac2O, pyridine) produced aziridine 13 in
79% yield. In the 13C NMR spectrum of 13, the chemical shift of
signals for C-2 and C-3 appeared at 42.6 ppm and 40.5 ppm, re-
spectively, an indication of aziridine ring formation. Compound 13
is crystalline and further support for the structure was obtained
from an X-ray diffraction study. The structure (Fig. 3a) showed that
The final step in the synthesis of 4 involved cleavage of the
allyl glycoside in 13. This cleavage was achieved by first rearrange-
ment of the allyl ether to the vinyl ether in the presence of
(1,5-cyclooctadiene)bis(methyldiphenylphosphine)iridium(I) hexa-
fluorophosphate and H2.38 Next, treatment with trimethylamine
y
Crystallographic data (excluding structure factors) for 13 have been deposited
with the Cambridge Crystallographic Data Centre as supplementary publication
number CCDC 917385. Copies of the data can be obtained, free of charge, on ap-
plication to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK, fax: þ44 (0)1223 336033
or e-mail: deposit@ccdc.cam.ac.uk.

4278
M.F. Ahmed, T.L. Lowary / Tetrahedron 69 (2013) 4276e4284
Fig. 3. Crystal structure of 13. (a) Depicts the orientation of the aziridine ring relative to the allyl and benzoyloxymethyl groups. (b) Shows the different orientations of the acetyl
group relative to the furanose ring in the two molecules in the unit cell.
N-oxide and osmium tetroxide39 resulted in cleavage of the vinyl
ether to give the expected hemiacetal (4) in 98% yield over the two
steps (a/b 1:7). Finally, reaction of 4 with trichloroacetonitrile in the
corresponding epoxide-functionalized compounds. As described
below, in the other glycoside product, where H-1 is cis to the azir-
idine moiety, the 1JC-1,H-1 value was w175 Hz. Thus, it appears that
the trends in 1JC-1,H-1 magnitudes established in the epoxide series
also apply for these aziridine-containing compounds.
presence of DBU at room temperature produced 5 in excellent yield.40
We also explored an alternate route to 4 and 5, starting from p-
methoxyphenyl (PMP) glycoside 1441 (Scheme 2). As detailed in
Scheme S1 (see Supplementary data), 14 could be converted to the
expected aziridine 15 using a route analogous to that used to
prepare 13. However, attempted cleavage of the PMP glycoside
using with ceric ammonium nitrite (CAN)42 or 2,3-dichloro-5,6-
dicyanobenzoquinone(DDQ)43 led to decomposition of the mole-
cule and hence this approach was abandoned.
2.3. Stereoselectivity of glycosylation reactions with 4 and 5
To assess the ability of 4 and 5 to act as glycosyl donors, various
alcohol acceptors were used (16e23, Fig. 4). Included were aliphatic
primary, secondary, and tertiary alcohols, as well as primary and
secondary carbohydrate alcohols.
2.2. Method for establishing anomeric stereochemistry in
glycoside products
RO
O
O
H3C OR
7
OCH3
OR
With 4 and 5 in hand, we explored their ability to serve as
glycosyl donors. However, before doing that, an unambiguous
method for establishing anomeric stereochemistry in the products
was needed. Previous studies have reported11 that the value of the
1JC-1,H-1 is the only reliable method for determining the stereo-
chemistry at the anomeric center in 2,3-anhydrofuranosides. In
these studies, 1JC-1,H-1 was shown to fall between 163 and 169 Hz
when H-1 is trans to the oxirane ring. When H-1 is cis to the ep-
oxide moiety 1JC-1,H-1 ranged between 174 and 178 Hz.
16, R = H
24, R = R'
17, R = H
25, R = R'
18, R = H
26, R = R'
Ph
O
OR
O
BzO
O
O
OR
RO
BnO
OPMP
OCH3
N3
19, R = H
27, R = R'
20, R = H
28, R = R'
OR
21, R = H
29, R = R'
To determine if this trend was also observed in 2,3-
1
aziridinoglycoisdes, we measured the values of the JC-1,H-1 in 13
BzO
O
and 15. The X-ray structure for 13 unequivocally established the
relative stereochemistry between the aziridine and the anomeric
substituent. The similarities in NMR spectra between 13 and 15, as
well as the route by which the compound was synthesized, allowed
us to conclude that 15 also has a trans-relationship between the C-
1eH-1 bond and the aziridine group. For both 13 and 15, the 1JC-1,H-1
value is 169.1 Hz, which is consistent with the trends observed in the
OR
R' =
N
Ac
22, R = H
30, R = R'
23, R = H
31, R = R'
Fig. 4. Acceptors studied (16e23) in glycosylation reactions and possible products
(24e31).
BzO
OH
HO
6 steps
O
CAN, H2O, THF or
Decomposition
O
DDQ, H2O, CH2Cl2
OPMP
See Figure S1
N
Ac
15
OPMP
HO
14
Scheme 2. Attempted synthesis of 4 via PMP glycoside intermediates 14 and 15.

M.F. Ahmed, T.L. Lowary / Tetrahedron 69 (2013) 4276e4284
4279
In situ activation of 4 was performed using the Gin glycosylation
protocol.44 In this reaction, the hemiacetal is activated by the use of
trifluoromethanesulfonic anhydride and dimethyl sulfide in the
presence of an acid scavenger (2,4,6-tri-tert-butyl-pyridine, TTBP).
After an appropriate time, a solution of acceptor alcohol is added
dropwise and the reaction stirred until complete. Under these
conditions we propose that the initially formed oxacarbenium ion
pair (32, Fig. 5) exists in equilibrium with two glycosyl triflates (33
and 34) that react in an SN2-like fashion with the alcohol when it is
added. Previous work on 2,3-anhydrosugar glycosyl triflates sug-
The results presented in Table 1 can be rationalized based on
the pathway shown in Fig. 5. With the less hindered alcohols,
modest
SN2-like displacement between the acceptor and the
The formation of the -glycoside could arise from the reaction
between the -triflate 34 and the alcohol. Alternatively, the oxa-
carbenium ion pair 32 could be the immediate precursor to both
glycosides, although the -glycoside 36 would be expected to be
favored for steric reasons. The decreasing -selectivity seen as the
a
-selectivity results, which could be the result of a direct
b-triflate 33.
b
a
b
a
steric bulk of the alcohols increases could result from steric hin-
drance between the acetylated aziridine moiety in 33 and the
nucleophile (Fig. 6). This would lead to an increase in product
formation through 32 or 34.
gests that the
b-triflate 33 should be more stable than the a-triflate
34.45 Hence, if this reaction manifold is operating, the favored
product should be the
a
-glycoside 35.
OTf
BzO
BzO
BzO
O
O
ROH
OR
35
N
Ac
N
Ac
β-triflate
33
BzO
BzO
O
O
(CH3)2S
Tf2O
major
OTf
OH
N
N
32
BzO
OR
Ac
Ac
O
N
O
ROH
4
OTf
N
Ac
36
α-triflate
34
minor
Ac
Fig. 5. Plausible mechanistic pathway for glycosylations with 4.
OTf
BzO
O
As illustrated in Table 1, under these conditions, all of the
simple alcohols were glycosylated as was the primary carbohy-
drate alcohol 18. In contrast, neither of the secondary carbohy-
drate alcohols (20 or 21) led to a product. In these cases, unreacted
donor was observed. For those reactions in which a product was
N
O
R
H
O
formed, the yields were generally good; however, the
selectivities were modest. The best results were obtained with
benzyl alcohol (16), which gave the product in a 2.6:1 ratio.
With the more sterically encumbered tertiary alcohols 22 and 23,
the selectivities were lower (w1.5:1 ). In general, the glyco-
a/b stereo-
33
Fig. 6. Proposed negative steric interactions between the aziridine moiety in 33 and
a/b
alcohols.
a/b
We next explored the glycosylation of the trichloroacetimidate
5. These reactions involved the addition of 5 to a solution of the
alcohol in dichloromethane, followed by the dropwise addition of
TMSOTf. We also explored the effect of diethyl ether on the selec-
tivity of the glycosylation for some acceptors. Overall, the trends
observed in reactions with 4 are also observed with 5 (Table 2).
sylation selectivity decreased as the size of the acceptor alcohol
increased. In all cases, the anomeric stereochemistry was de-
1
termined by measurement of the JC-1,H-1 values of the purified
products. For all of the a-glycosides, this value ranged from 167.4
to 169.1 Hz and for all of the
174.5 Hz and 177.2 Hz.
b-glycosides this value was between
Table 2
Glycosylation of alcohols 16e23 with 5a
Entry
Solvent
Acceptor
Product
Yield (%)
a/b
ratiob
Table 1
Glycosylation of alcohols 16e23 with 4a
1
2
3
4
5
6
7
8
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
16
17
18
19
20
21
22
23
16
17
22
24
25
26
27
28
29
30
31
24
25
30
67
72
72
62
d
2.2:1
2.8:1
4.8:1
2.8:1
d
Entry
Acceptor
Product
Yield (%)
a/b
ratiob
1
2
3
4
5
6
7
8
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
81
74
85
78
d
2.6:1
1.8:1
2.4:1
1.7:1
d
d
d
71
70
68
69
75
1.2:1
1.6:1
4.0:1
3.6:1
1.8:1
d
d
9
10
11
9:1 CH2Cl2eEt2O
9:1 CH2Cl2eEt2O
9:1 CH2Cl2eEt2O
78
76
1.6:1
1.3:1
a
a
Conditions: see Method A in experimental.
Conditions: see Methods B or C in experimental.
b
b
Ratio determined by the integration of the H-1 signal of the glycosides in the 1
H
Ratio determined by the integration of the H-1 signal of the glycosides in the 1
H
NMR spectrum of the crude products.
NMR spectrum of the crude products.

4280
M.F. Ahmed, T.L. Lowary / Tetrahedron 69 (2013) 4276e4284
The glycosylations are modestly
hindrance on the alcohol increases, the selectivity decreases. When
comparing the two donors, the use of the imidate donor generally
a
-selective, and, as the steric
modification of the nitrogen protecting group, for example, by re-
placement with a carbamate, could also be anticipated to influence
the stereochemical outcome of the reaction via altering the elec-
tronic character of the nitrogen.16 However, the selectivities ob-
served here, and the limitation that secondary carbohydrate
alcohols cannot be glycosylated by these species, suggest these
donors have limited future application in the synthesis of complex
glycans.
gives better
a small amount of ether is added to the reactions involving 5, the
-selectivity increases further for some alcohols (Table 2, compare
a-selectivity than the hemiacetal. Finally, when
a
entries 1 and 9, entries 2 and 10, and entries 7 and 11).
We propose that the mechanism of the reaction involves
a pathway as shown in Fig. 7.40 Activation of 5 by TMSOTf would
lead to 37, which can proceed down one of two pathways. Direct
SN2-like displacement on 37 by the alcohol will lead directly to the
4. Experimental section
4.1. General methods
a
-glycoside 35. On the other hand, 37 can also dissociate into an
oxacarbenium ion pair 38, which can react with alcohols to gen-
erate a mixture of and glycosides 39. The modest increase in
a
b
a-
Starting materials and reagents used in reactions were pur-
chased from commercial sources, SigmaeAldrich and Fluka, and
were used without further purification, unless stated otherwise.
Solvents used in reactions were purified by passage through col-
umns of alumina and copper under argon pressure. Unless noted
differently, all reactions were carried out under a positive pressure
of argon/nitrogen and were monitored by TLC on silica gel G-25
UV254 (0.25 mm, E. Merck). Spots were detected under UV light or
by charring with 10% H2SO4 in ethanol or charring with a solution of
selectivity with some alcohols in the presence of diethyl ether46 can
be rationalized by the formation of adduct 40 (from 38), which
would lead to the increase amount of attack cis to the aziridine.
Similar to what was proposed for the reactions involving hemi-
acetal 4, we speculate that as the steric hindrance on the alcohol
increases, direct SN2 attack on intermediates, such as 37 and 39
become disfavored and that the reaction proceeds through species,
such as 38. This pathway is anticipated to be less
a
-selective.
BzO
O
TMS
H
OTf
N
OTf
NH
TMS
CCl3
b
a, –H+
OR
N
Ac
O
CCl3
BzO
O
BzO
O
O
R
35
O
a
N
Ac
N
Ac
b
H
BzO
O
OTf
37
5
OEt2
N
Ac
38
BzO
ROH
O
–
H+
BzO
OTf
R
O
OR
N
Ac
O
N
Ac
H
39
40
Fig. 7. Plausible mechanistic pathway for glycosylations with 5.
3. Conclusion
anisaldehyde in ethanol, acetic acid, and H2SO4. Solvents were
evaporated under reduced pressure and below 60 ꢁC (bath), and
organic solutions of crude products were dried over anhydrous
Na2SO4. Column chromatography was performed on Silica Gel 60
In summary, we describe here the synthesis of two aziridine-
containing glycosyl donors, hemiacetal 4 and trichloroacetimidate
5. The former is obtained in nine steps from
D-arabinose and the
(40e60 mM) and the ratio between silica gel and crude product
latter in one additional step. When the ability of these compounds
to glycosylate alcohols was studied, the major products were those
in which the newly formed glycosidic bond was cis to the aziridine
moiety. Trichloroacetimidate 5 provides the products with mar-
ginally better stereoselectivity than 4, and the addition of ether to
the reaction mixture modestly enhances this selectivity in some
cases.
These results suggest that these species behave analogously to
the epoxide-containing (2,3-anhydrosugar) donors we have pre-
viously investigated. However, the stereoselectivities with the
aziridine substrates are lower. We attribute this to the need for
a protecting group on the aziridine nitrogen. The steric bulk of this
group could hinder the approach of the nucleophile into an elec-
trophilic intermediate (e.g., 33, Fig. 6) from the face cis to the
aziridine moiety. In the epoxide series, a protecting group is not
necessary. Further refinement of this reaction through the use of
other donor types (e.g., thioglycosides, sulfoxides), or other nitro-
ranged from 100 to 50:1 (w/w). Optical rotations were measured at
21ꢂ2 ꢁC at the sodium D line (589 nm) on a PerkineElmer polar-
imeter and are in units of deg mL/(dm g). 1H NMR spectra were
recorded at 400 or 500 MHz and 13C NMR spectra at 100 or
125 MHz. 1H chemical shifts were referenced to TMS (0.0, CDCl3) or
internal CD3OD (3.31, CD3OD). 13C chemical shifts were referenced
to CDCl3 (77.00, CDCl3) or CD3OD (49.15, CD3OD). Peaks assign-
ments were made by 2D NMR (gCOSY, gHSQC, and gHMBC) ex-
periments. IR spectra were obtained as film (by application of
a solution of the compound in CHCl3 to an NaCl plate followed by
evaporation of the solvent). Electrospray mass spectra were recor-
ded on samples suspended in mixtures of THF and CH3OH with
added NaCl. All acceptors were either commercially available or
prepared as previously reported.6 Product yields from glycosylation
reactions are shown in Tables 1 and 2. Crystallographic data (ex-
cluding structure factors) for 13 has been deposited with the
Cambridge Crystallographic Data Centre as supplementary publi-
cation nos. CCDC 917385. Copies of the data can be obtained, free of
gen protecting groups could enhance the a-selectivity. In addition,

M.F. Ahmed, T.L. Lowary / Tetrahedron 69 (2013) 4276e4284
4281
charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ,
UK, fax: þ44 (0)1223 336033 or e-mail: deposit@ccdc.cam.ac.uk.
triphenylphosphine oxide precipitated upon trituration with cold
diethyl ether. The triphenylphosphine oxide was filtered off and the
filtrate was concentrated. The resulting residue was purified by
chromatography (hexaneseEtOAc, 7:1) to obtain compound 10
(3.7 g, 82%) as a white crystalline solid. Rf 0.62 (hexaneseEtOAc,
4.2. N-Acetyl-2,3-aziridino-5-O-benzoyl-2,3-dideoxy-D-ribo-
furanose (4)
4:1); [
a
]
þ41.2 (c 1.0, CHCl3); 1H NMR (400 MHz, CDCl3, dH
)
D
A solution of [Ir(COD)(PMePh2)2]PF6 (0.12 g, 0.14 mmol) in THF
(24 mL) was stirred under a hydrogen atmosphere for 20 min at
room temperature. The catalyst immediately lost its pink color and
started to dissolve. The clear solution was injected carefully into
a solution of 13 (1.4 g, 4.41 mmol) dissolved in THF (46.4 mL) and
the reaction mixture was stirred overnight at room temperature
under an argon atmosphere. Concentration of the mixture resulted
in a colorless oil, which was dissolved in dichloromethane (58 mL).
Trimethylamine N-oxide dehydrate (0.75 g, 6.7 mmol) and osmium
tetroxide (11.8 mg) were added to the solution and the reaction
mixture was stirred for another 12 h at room temperature. The
reaction solution was then concentrated and purified by column
chromatography (hexaneseEtOAc 1:1) to afford 4 (1.2 g, 98%) as
8.12e8.03 (m, 2H, Ar), 7.62e7.52 (m, 1H, Ar), 7.51e7.40 (m, 2H, Ar),
5.99e5.83 (m, 1H, CH]CH2), 5.31 (ddd, 1H, J¼1.6, 3.2, 17.1 Hz, CH]
CH2), 5.22 (ddd, 1H, J¼1.6, 2.8, 10.3 Hz, CH]CH2), 5.15 (s, 1H, H-1),
4.55 (dd, 1H, J¼6.0, 11.5 Hz, H-5), 4.50 (dd, 1H, J¼6.0, 11.5 Hz, H-5),
4.36 (dd, 1H, J¼5.6, 6.0 Hz, H-4), 4.27 (dddd, 1H, J¼1.2, 1.2, 5.2,
12.8 Hz, OCH2CH]CH2), 4.06 (dddd, 1H, J¼1.2, 1.2, 6.0, 12.8 Hz,
OCH2CH]CH2), 3.83 (dd, 1H, J¼0.8, 2.8 Hz, H-2), 3.73 (d, 1H,
J¼2.8 Hz, H-3); 13C NMR (125.3 MHz, CDCl3, dC) 166.2 (C]O), 133.7
(CH]CH2), 133.1 (AreC), 129.7 (AreC), 129.7 (AreC), 128.3 (AreC),
117.7 (CH]CH2), 100.5 (C-1), 74.0 (C-4), 69.0 (OCH2CH]CH2), 62.8
(C-5), 56.3 (C-2), 54.1 (C-3). HRMS (ESI) calcd for (MþNa)
C15H16O5þNa: 299.1563, found 299.1560.
a colorless oil and as a mixture of isomers (
a/b
-1.0:7.0), Rf 0.21 (1:1,
4.5. Allyl 3-azido-5-O-benzoyl-3-deoxy-a-D-arabinofurano-
side (11)
hexaneseEtOAc); 1H NMR (500 MHz, CDCl3, dH) 8.11e8.08 (m,
2.38H, Ar), 7.63e7.58 (m, 1.27H, Ar), 7.51e7.46 (m, 2.42H, Ar), 5.52
(d, 0.15H, J¼1.0 Hz, H-1
a
), 5.51 (s, 1H, H-1
b
), 4.58e4.48 (m, 2.64H),
To a solution of compound 10 (2.6 g, 9.49 mmol) in EtOHeH2O
(9:1, 95 mL) were added NaN3 (3.67 g, 56.5 mmol) and NH4Cl
(5.03 g, 94.1 mmol). The reaction mixture was heated at reflux for
48 h, cooled to room temperature, and extracted with EtOAc
(2ꢃ50 mL). The combined organic extracts were dried over
Na2SO4, filtered, and the solvent was removed under reduced
pressure. The product was purified by column chromatography
(5:1, hexaneseEtOAc) to yield 11 (2.57 g, 85%, 9% starting material
10 was also recovered) as a colorless syrup: Rf 0.25 (5:1, hex-
4.44e4.35 (m, 1.24H), 4.34e4.30 (m, 0.34H), 3.44 (d, 1H, J¼4.0 Hz),
3.41 (dd, 0.17H, J¼1.0, 4.0 Hz), 3.38e3.34 (m, 1H), 2.21 (s, 0.42H,
acetate CH3a), 2.10 (s, 3H, acetate CH3b); 13C NMR (125.7 MHz,
CDCl3, dC) 180.8 (C]O), 179.7 (C]O), 166.3 (C]O), 166.0 (C]O),
133.5 (AreC), 133.4 (AreC), 129.7 (AreC), 129.6 (AreC), 129.4
(AreC), 128.6 (AreC), 128.6 (AreC), 128.5 (AreC), 97.9 (C-1
(C-1 ), 74.9 (C-4 ), 74.7 (C-4 ), 65.3 (C-5 ), 65.0 (C-5 ), 43.6 (C-2
41.5 (C-2 ), 40.9 (C-2 ), 40.8 (C-2 ), 23.9 (CH3), 23.6 (CH3). HRMS
(ESI) calcd for (MþNa) C14H15NO5þNa: 300.0847, found 300.0845.
a
), 95.3
b
b
a
b
a
b
),
a
a
b
aneseEtOAc); [
a]
D þ100.6 (c 1.5, CHCl3); 1H NMR (500 MHz, CDCl3,
dH) 8.12e8.03 (m, 2H, Ar), 7.62e7.52 (m, 1H, Ar), 7.51e7.40 (m, 2H,
Ar), 5.94e5.86 (m, 1H, CH]CH2), 5.31 (ddd, 1H, J¼1.6, 3.2, 17.1 Hz,
CH]CH2), 5.22 (ddd, 1H, J¼1.6, 2.8, 10.3 Hz, CH]CH2), 5.05 (d, 1H,
J¼1.5 Hz, H-1), 4.58 (dd, 1H, J¼4.0, 12.0 Hz, H-5), 4.50 (dd, 1H,
J¼4.5, 12.0 Hz, H-5), 4.35e4.20 (m, 3H, H-4, 2ꢃ OCH2CH]CH2),
4.05 (ddd, 1H, J¼1.0, 6.0, 13.0 Hz, H-2), 3.80 (dd, 1H, J¼3.5, 7.0 Hz,
H-3), 3.12 (br, 1H); 13C NMR (125.3 MHz, CDCl3, dC) 166.4 (C]O),
133.6 (CH]CH2), 133.4 (AreC), 129.8 (AreC), 129.7 (AreC), 128.5
(AreC), 117.7 (CH]CH2), 106.8 (C-1), 80.9 (C-2), 79.1 (C-4), 68.5
(OCH2CH]CH2), 67.5 (C-3), 63.8 (C-5); IR (film) 3467.2 (br),
3061.9, 2956.1, 2107.2 (N]N]N), 1723.5 (C]O), 1275.4 (CeO).
HRMS (ESI) calcd for (MþNa) C15H17N3O5þNa: 342.1066, found
342.1056.
4.3. N-Acetyl-2,3-aziridino-5-O-benzoyl-2,3-dideoxy-b-D-ri-
bofuranosyl trichloroacetimidate (5)
To
chloroacetonitrile (1.26 mL, 12.6 mmol) in dichloromethane
(18.0 mL) cooled to 0 ꢁC was added a solution of DBU (13.48
L,
a stirring solution of 1 (0.5 g, 1.8 mmol) and tri-
m
0.09 mmol) in dichloromethane (0.6 mL) over a period of 5 min. The
reaction mixture then warmed to room temperature over 10 min
and was stirred for 2 h at room temperature. The solution then
concentrated at room temperature under reduced pressure, and the
residue was purified by silica gel flash chromatography (6:4, hex-
aneseEtOAc with 0.5% Et3N, Rf 0.28) to give trichloroacetimidate 2
(0.74 g, 98%) as an amorphous white solid; [
a
]
D ꢀ25.1 (c 0.6, CHCl3);
1H NMR (500 MHz, CDCl3, dH) 8.68 (s, 1H), 8.08e8.06 (m, 2H, Ar),
7.63e8.59 (m, 1H, Ar), 7.50e7.46 (m, 2H, Ar), 6.56 (s, 1H, H-1), 4.73
(dd, 1H, J¼6.0, 7.0 Hz, H-4), 4.53 (dd, 1H, J¼7.0, 12.5 Hz, H-5), 4.49
(dd,1H, J¼6.0,11.5 Hz, H-5), 3.65 (d,1H, J¼4.0 Hz, H-2), 3.61 (dd,1H,
4.6. Allyl 3-azido-5-O-benzoyl-3-deoxy-2-O-p-toluene-
sulfonyl-a-D-arabinofuranoside (12)
A solution of compound 11 (2.4 g, 7.51 mmol) dissolved in
dichloromethane (28 mL) and pyridine (4.5 mL) was treated at 0 ꢁC
with p-toluenesulfonyl chloride (5.3 g, 27.8 mmol), and the reaction
mixture was stirred for 50 h at room temperature under argon. The
reaction mixture was quenched by the addition of a small piece of
ice and then diluted with dichloromethane (22 mL). The organic
layer was washed with a satd aq NaHCO3 solution and then water.
The crude solution was dried over anhydrous Na2SO4, filtered, and
concentrated under reduced pressure. The residue was purified by
column chromatography (7:1, n-hexaneseEtOAc) to yield 12
J¼4.0 Hz, H-3), 2.22 (s, 3H, CH3); 13C NMR (125.7 MHz, CDCl3, dC
)
176.4 (C]O), 163.5 (C]O), 158.2 (C]NH), 130.8 (Ar), 127.2 (Ar),
126.8 (Ar), 125.9 (Ar), 95.9 (C-1), 89.0 (CCl3), 74.9 (C-4), 62.8 (C-5),
40.5 (C-2), 39.2 (C-3), 22.1 (CH3); JC-1,H-1¼183.1 Hz. HRMS (ESI) calcd
for (MþNa) C16H15Cl3N2O5þNa: 442.9943, found 442.9943.
4.4. Allyl 2,3-anhydro-5-O-benzoyl-a-D-lyxofuranoside (10)
To a solution of 99 (3.10 g, 16.30 mmol) in THF (180 mL), tri-
phenylphosphine (10.73 g, 40.76 mmol) and benzoic acid (3.0 g,
24.46 mmol) were added. The resulting mixture was then cooled to
(2.81 g, 79%) as an oil. Rf 0.35 (7:1, hexaneseEtOAc); [
a
]
D
þ86.2 (c
1.0, CHCl3); 1H NMR (500 MHz, CDCl3, dH) 8.10e8.04 (m, 2H, Ar),
7.82e7.77 (m, 2H, Ar), 7.61e7.56 (m, 1H, Ar), 7.49e7.40 (m, 2H,
Ar),7.35 (d, 2H, J¼8.0 Hz, Ar), 5.57e5.55 (m, 1H, CH]CH2), 5.25
(ddd, 1H, J¼1.5, 3.5, 17.0 Hz, CH]CH2), 5.18 (ddd, 1H, J¼1.0, 2.5,
11.5 Hz, CH]CH2), 5.08 (s, 1H, H-1), 4.78 (d, 1H, J¼2.5 Hz, H-2), 4.55
(dd, 1H, J¼4.0, 12.0 Hz, H-5), 4.46 (dd, 1H, J¼4.0, 12.0 Hz, H-5), 4.18
0
ꢁC and diisopropyl azodicarboxylate (3.86 mL, 19.5 mmol) was
added dropwise over a period of 10 min. The reaction mixture was
allowed to stir at room temperature for 2 h under an argon
atmosphere. The solution was subsequently concentrated under
reduced pressure to yield a crude oil from, which most of the

4282
M.F. Ahmed, T.L. Lowary / Tetrahedron 69 (2013) 4276e4284
ꢀ
(ddd, 1H, J¼4.0, 4.0,7.0 Hz, H-4), 4.12 (dddd, 1H, J¼1.5, 1.5, 5.0,
13.0 Hz, OCH2CH]CH2), 3.96 (dd, 1H, J¼3.0, 6.5 Hz, H-3), 3.94
(dddd, 1H, J¼1.5, 1.5, 6.5, 13.0 Hz, OCH2CH]CH2), 2.94 (s, 3H, CH3);
13C NMR (125.3 MHz, CDCl3, dC) 166.1 (C]O), 145.7 (Ar), 133.4
(CH]CH2), 133.1, 132.6, 130.2, 129.8, 129.3, 128.5, 128.1, 118.0 (CH]
CH2), 104.1 (C-1), 87.4 (C-2), 79.3 (C-4), 68.2 (OCH2CH]CH2), 65.9
(C-3), 62.9 (C-5), 21.7 (CH3); IR (film) 3060.9, 2946.7, 2111.0 (N]N]
N), 1724.1 (C]O), 1273.0 (CeO). HRMS (ESI) calcd for (MþNa)
C22H23N3O7SþNa: 496.1153, found 496.1151.
containing 4 A molecular sieves (10 mg) was added a solution of
trichloroacetimidate 5 (50 mg, 0.12 mmol) dissolved in dichloro-
methane (1.0 mL). A solution of TMSOTf (0.05 equiv) in dichloro-
methane (0.16 mL) was added dropwise to the reaction mixture
over a period of 5 min. The resulting mixture was stirred at this
temperature for 15 min, then another 15 min at ꢀ20 ꢁC, and finally
warmed slowly to ꢀ5 ꢁC over 1 h. After quenching the acid by the
addition of Et3N, the reaction mixture was diluted with dichloro-
methane (3 mL) and filtered through Celite. The filtrate was con-
centrated under reduced pressure to give a crude residue that was
purified by column chromatography to afford products shown in
Table 2.
4.7. Allyl N-acetyl-2,3-aziridino-5-O-benzoyl-2,3-dideoxy-a-D-
ribofuranoside (13)
To a solution of azide 12 (2.2 g, 4.6 mmol) in THF (5.2 mL), water
(0.41 mL) and triphenylphosphine (3.02 g, 11.5 mmol) were added.
The resulting mixture was stirred for 20 h at room temperature. The
solution then dried over Na2SO4 and concentrated under high
vacuum resulting in a colorless crude oil. Without further purifi-
cation, DMF (24 mL) and triethylamine (0.83 mL) were added to the
crude product at room temperature. The reaction mixture was
stirred at 100 ꢁC for 20 h and then cooled to room temperature.
Pyridine (27 mL) and acetic anhydride (4.6 mL) were then added to
the mixture cooled at 0 ꢁC. After stirring for 4 h at room temper-
ature, the mixture was extracted with EtOAc (3ꢃ30 mL). The or-
ganic phases were combined, washed with a satd aq NaHCO3
solution and then water. The organic layer was dried over anhy-
drous Na2SO4, filtered, and the solvent was evaporated under
reduced pressure. The residue was purified by column chroma-
tography (7:1, hexaneseEtOAc) to yield 13 (2.81 g, 79%) as a white
4.8.3. Method C: glycosylation with imidate 5 using TMSOTf in di-
chloromethane and 10% diethyl ether.40 The donor 5 (50 mg,
0.12 mmol) was dissolved in dichloromethane (1.0 mL) and then
added to a solution of alcohol (16, 17 or 22) dissolved in dichloro-
ꢀ
methane (1.0 mL) and diethyl ether (0.1 mL) containing 4 A mo-
lecular sieves (10 mg, stirred already for 10 min) at ꢀ25 ꢁC. At this
temperature, a solution of TMSOTf (0.05 equiv) in dichloromethane
(0.16 mL) was added dropwise over 5 min. The resulting mixture
was stirred for 15 min followed by another 15 min at ꢀ20 ꢁC, and at
last warmed slowly to ꢀ5 ꢁC over 1 h. The reaction mixture then
quenched by the addition of Et3N (0.56
mL), diluted with
dichloromethane (3 mL), and filtered through Celite. The filtrate
was concentrated to give a crude residue that was purified by
column chromatography to afford the products shown in Table 2
(Results and discussion section).
solid: Rf 0.35 (2:1, hexaneseEtOAc); [
a
]
ꢀ59.6 (c 1.0, CHCl3); 1H
D
NMR (500 MHz, CDCl3, dH) 8.01e8.04 (m, 2H, Ar), 7.60e7.56 (m, 1H,
Ar), 7.47e7.41 (m, 2H, Ar), 5.95e5.86 (m, 1H, CH]CH2), 5.65 (d, 1H,
J¼1.5 Hz, H-1), 5.3 (ddd, 1H, J¼1.5, 3.5, 17.0 Hz, CH]CH2), 5.19 (ddd,
1H, J¼1.0, 2.5, 10.5 Hz, CH]CH2), 4.71 (dd, 1H, J¼4.0, 4.0 Hz, H-4),
4.5 (dd, 1H, J¼4.0, 12.0 Hz, H-5), 4.38 (dd, 1H, J¼4.0, 12.0 Hz, H-5),
4.32 (dddd, 1H, J¼1.5, 1.5, 5.0, 13.0 Hz, OCH2CH]CH2), 4.15 (dddd,
1H, J¼1.5, 1.5, 6.5, 13.0 Hz, OCH2CH]CH2), 3.4 (dd, 1H, J¼1.5, 4.5 Hz,
H-2), 3.3 (d, 1H, J¼4.0 Hz, H-3), 3.22 (s, 3H, CH3); 13C NMR
(125.3 MHz, CDCl3, dC) 180.8 (C]O), 166.1 (C]O), 133.6 (AreC),
133.4 (CH]CH2), 129.6 (AreC), 129.5 (AreC), 128.6 (AreC), 117.6
(CH]CH2), 101.5 (C-1), 74.9 (C-4), 70.9 (OCH2CH]CH2), 65.2 (C-5),
42.6 (C-2), 40.5 (C-3), 24.0 (CH3); JC-1,H-1¼169.1 Hz. HRMS (ESI)
calcd for (MþNa) C17H19NO5þNa: 340.1160, found 340.1145.
4.9. Benzyl N-acetyl-2,3-aziridino-5-O-benzoyl-2,3-dideoxy-
a-
D-ribofuranoside (24
a)
The compound was isolated after chromatography (hex-
aneseEtOAc, 3:1) as a colorless oil. Rf 0.26 (hexaneseEtOAc, 2:1);
1H NMR (500 MHz, CDCl3, dH) 8.07e8.03 (m, 2H, Ar), 7.62e7.58 (m,
1H, Ar), 7.46e7.42 (m, 2H, Ar), 7.26e7.22 (m, 5H, Ar), 5.39 (d, 1H,
J¼1.5 Hz, H-1), 4.87 (d, 1H, J¼12.0 Hz, PhCH2), 4.76 (dd, 1H, J¼4.0,
4.0 Hz, H-4), 4.59 (d, 1H, J¼12.0 Hz, PhCH2), 4.52 (dd, 1H, J¼4.0,
12.0 Hz, H-5), 4.39 (dd, 1H, J¼4.0, 12.0 Hz, H-5), 3.78 (dd, 1H, J¼1.0,
3.5 Hz, H-2), 3.78 (d,1H, J¼4.0 Hz, H-3), 2.15 (s, 3H, acetate CH3); 13
C
NMR (125.7 MHz, CDCl3, dC) 180.7 (C]O), 166.0 (C]O), 136.9
(AreC), 133.4 (AreC), 129.5 (AreC), 129.4 (AreC), 128.5 (AreC),
128.4 (AreC),128.0 (AreC),127.9 (AreC),101.1 (C-1), 74.7 (C-4), 71.6
(OCH2), 65.2 (C-5), 42.5 (C-2), 40.4 (C-3), 24.1 (CH3); JC-1,H-
4.8. General procedures for glycosylation reactions
¼168.3 Hz. HRMS (ESI) calcd for (MþNa) C21H11NO5þNa: 390.1316,
1
4.8.1. Method A: glycosylation with 4 using (CH3)2S and Tf2O.44 To
found 390.1314.
a
stirring solution of N-acetyl-2,3-aziridino-5-O-benzoyl-2,3-
dideoxy- -ribofuranose (4, 35 mg, 0.13 mmol), 2,4,6-tri-tert-
butylpyridine (140.3 mg, 0.56 mmol), and dimethyl sulfide
(18.64 L, 0.3 mmol) in dichloromethane (1.8 mL) was added tri-
fluoromethanesulfonic acid anhydride (31.85 L, 0.19 mmol,
D
4.10. Benzyl N-acetyl-2,3-aziridino-5-O-benzoyl-2,3-dideoxy-
m
b-D
-ribofuranoside (24
b)
m
1.5 equiv) at ꢀ45 ꢁC under an argon atmosphere. The resulting
solution was stirred for 1 h at this temperature, followed by 15 min
at 0 ꢁC and finally another 15 min at room temperature. A solution
of an alcohol (20 to 27, 0.19 mmol, 1.5 equiv) in dichloromethane
(0.44 mL) was then added dropwise. The reaction mixture then
stirred for 12 h at room temperature, and diluted with dichloro-
methane (20 mL). The diluted solution was washed with a satd
aq NaHCO3 and water. The organic layer was dried, filtered, and
concentrated. The crude residue was purified by chromatography
to afford the products shown in Table 2.
The compound was isolated after chromatography (hex-
aneseEtOAc, 3:1) as a colorless oil. Rf 0.28 (hexaneseEtOAc, 2:1);
1H NMR (500 MHz, CDCl3, dH) 8.10e8.05 (m, 2H, Ar), 7.61e7.54
(m, 1H, Ar), 7.49e7.40 (m, 2H, Ar), 7.38e7.31 (m, 5H), 5.29 (s, 1H,
H-1), 4.78 (d, 1H, J¼11.5 Hz, PhCH2), 4.63 (dd, 1H, J¼6.5, 6.5 Hz,
H-4), 4.56 (d, 1H, J¼11.5 Hz, PhCH2), 4.51 (dd, 1H, J¼6.0, 11.5 Hz,
H-5), 4.48 (dd, 1H, J¼6.5, 11.5 Hz, H-5), 3.46 (d, 1H, J¼3.5 Hz, H-2),
3.42 (d, 1H, J¼4.0 Hz, H-3), 2.16 (s, 3H, acetate CH3); 13C NMR
(125.7 MHz, CDCl3, dC) 179.2 (C]O), 166.1 (C]O), 136.7 (AreC),
133.2 (AreC), 129.7 (AreC), 129.6 (AreC), 128.5 (AreC), 128.4
(AreC), 128.2 (AreC), 128.0 (AreC), 100.2 (C-1), 75.0 (C-4), 70.2
(OCH2), 64.8 (C-5), 42.8 (C-2), 40.7 (C-3), 23.7 (CH3); JC-1,H-
4.8.2. Method B: glycosylation with imidate 5 using TMSOTf in di-
chloromethane.40 To a stirring solution of an alcohol (16 to 23,
0.1 mmol, 0.8 equiv) in dichloromethane (1.0 mL) at ꢀ25 ꢁC
¼175.1 Hz. HRMS (ESI) calcd for (MþNa) C21H11NO5þNa:
1
390.1316, found 390.1314.

M.F. Ahmed, T.L. Lowary / Tetrahedron 69 (2013) 4276e4284
4283
4.11. n-Octyl N-acetyl-2,3-aziridino-5-O-benzoyl-2,3-dideoxy-
-ribofuranoside (25
7.52e7.48 (m, 2H, Ar), 5.24 (s, 1H, H-10), 4.97 (s, 1H, H-1), 4.61 (dd,
1H, J¼6.0, 7.0 Hz, H-40), 4.48 (dd, 2H, J¼7.0, 7.0 Hz, H-50), 4.19 (dd,
1H, J¼6.0,10.0 Hz, H-5), 3.96 (dd, 1H, J¼5.5,10.0 Hz, H-5), 3.63e3.74
(m, 3H, H-20, H-2, H-4), 3.43e3.47 (m, 2H, H-30, H-3), 3.41 (s,
a
-D
a)
The compound was isolated after chromatography (4:1, hex-
aneseEtOAc) as a colorless oil: Rf 0.40 (3:1, hexaneseEtOAc); 1H
NMR (500 MHz, CDCl3, dH) 8.09e8.01 (m, 2H, Ar), 7.65e7.52 (m, 1H,
Ar), 7.51e7.40 (m, 2H, Ar), 5.34 (d, 1H, J¼1.5 Hz, H-1), 4.76 (dd, 1H,
J¼4.0, 4.0 Hz, H-4), 4.53 (dd, 1H, J¼4.0, 12.0 Hz, H-5), 4.40 (dd, 1H,
J¼4.0, 12.0 Hz, H-5), 3.81 (ddd, 1H, J¼6.5, 7.0, 9.5 Hz, octyl OCH2),
3.53 (ddd, 1H, J¼6.5, 7.0, 9.0 Hz, octyl OCH2), 3.42 (dd, 1H, J¼1.5,
4.5 Hz, H-2), 3.31 (d, 1H, J¼4.0 Hz, H-3), 2.23 (s, 3H, acetate CH3),
1.71e1.58 (m, 4H, octyl CH2), 1.42e1.18 (m, 8H, octyl CH2), 0.95 (t,
3H, J¼6.8 Hz, octyl CH3); 13C NMR (125.7 MHz, CDCl3, dC) 180.8 (C]
O), 166.1 (C]O), 133.4 (AreC), 129.6 (AreC), 129.5 (AreC), 128.6
(AreC),102.5 (C-1), 74.3 (C-4), 70.8 (octyl OCH2), 65.3 (C-5), 42.6 (C-
2), 40.3 (C-3), 31.8 (octyl-CH2), 29.7 (octyl-CH2), 29.6 (octyl-CH2),
29.5 (octyl-CH2), 25.9 (octyl-CH2), 24.1 (acetate-CH3), 14.1 (octyl-
CH3); JC-1,H-1¼169.0 Hz. HRMS (ESI) calcd for (MþNa)
C22H31NO5þNa: 412.2099, found 412.2093.
3H,OCH3), 2.15 (s, 3H, acetate CH3); 13C NMR (125.7 MHz, CDCl3, dC
)
179.2 (C]O), 166.1 (C]O), 133.3 (AreC), 129.7 (AreC), 128.4
(AreC), 102.4 (azi-C-1), 101.4 (epo-C-1), 75.1 (C-40), 75.0 (C-4), 67.4
(C-5), 64.8 (C-50), 56.0 (C-2), 55.6 (C-3), 42.7 (C-20), 40.6 (C-30), 23.7
(OCH3); JC-1,H-1¼177.2 Hz. HRMS (ESI) calcd for (MþNa)
C20H23NO8þNa: 428.1321, found 428.1316.
4.15. Cyclohexyl N-acetyl-2,3-aziridino-5-O-benzoyl-2,3-
dideoxy-a-D-ribofuranoside (27a)
The compound was isolated after chromatography (hex-
aneseEtOAc, 4:1) as a colorless oil. Rf 0.32 (hexaneseEtOAc, 3:1);
1H NMR (500 MHz, CDCl3, dH) 8.12e8.03 (m, 2H, Ar), 7.62e7.55
(m, 1H, Ar), 7.51e7.46 (m, 2H, Ar), 5.46 (d, 1H, J¼1.0 Hz, H-1), 4.76
(dd, 1H, J¼4.0, 4.5 Hz, H-4), 4.53 (dd, 1H, J¼4.0, 12.0 Hz, H-5), 4.40
(dd, 1H, J¼4.5, 12.0 Hz, H-5), 3.57e3.64 (m, 1H, cyclohexyl CH),
3.38 (dd, 1H, J¼1.0, 4.0 Hz, H-2), 3.26 (d, 1H, J¼4.0 Hz, H-3), 2.18
(s, 3H, acetate CH3), 1.98e1.18 (m, 10H, cyclohexyl CH2); 13C NMR
(125.7 MHz, CDCl3, dC) 180.8 (C]O), 166.1 (C]O), 133.4 (AreC),
129.6 (2AreC), 128.6 (2AreC), 100.7 (C-1), 78.2 (cyclohexyl-CH),
73.9 (C-4), 65.3 (C-5), 42.9 (C-2), 39.8 (C-3), 33.1 (cyclohexyl CH2),
32.0 (cyclohexyl CH2), 29.7 (cyclohexyl CH2), 29.6 (cyclohexyl
CH2), 24.2 (OCH3), 24.1 (cyclohexyl CH2); JC-1,H-1¼168.2 Hz.
HRMS (ESI) calcd for (MþNa) C20H25NO5þNa: 382.1629, found
382.1623.
4.12. n-Octyl N-acetyl-2,3-aziridino-5-O-benzoyl-2,3-dideoxy-
b-
D
-ribofuranoside (25
b)
The compound was isolated after chromatography (4:1, hex-
aneseEtOAc) as a colorless oil: Rf 0.43 (3:1, hexaneseEtOAc); 1H
NMR (500 MHz, CDCl3, dH) 8.12e8.03 (m, 2H, Ar), 7.62e7.55 (m, 1H,
Ar), 7.51e7.46 (m, 2H, Ar), 5.17 (s, 1H, H-1), 4.60 (dd, 1H, J¼6.0,
6.5 Hz, H-4), 4.45 (d, 2H, J¼6.5 Hz, H-5), 3.75 (ddd, 1H, J¼6.5, 7.0,
9.5 Hz, octyl OCH2), 3.47 (ddd, 1H, J¼6.5, 7.0, 9.0 Hz, octyl OCH2),
3.43 (d, 1H, J¼3.5 Hz, H-2), 3.36 (d, 1H, J¼3.5 Hz, H-3), 2.18 (s, 3H,
acetate CH3), 1.64e1.50 (m, 4H, octyl CH2), 1.20e1.14 (m, 8H, octyl
CH2), 0.91 (t, 3H, J¼7.0 Hz, octyl CH3); 13C NMR (125.7 MHz, CDCl3,
dC) 179.2 (C]O), 166.1 (C]O), 133.2 (AreC), 129.7 (AreC), 129.6
(AreC),128.4 (AreC),100.9 (C-1), 74.6 (C-4), 68.9 (octyl-OCH2), 64.9
(C-5), 42.6 (C-2), 40.7 (C-3), 31.8 (octyl-CH2), 29.7 (octyl-CH2), 29.5
(octyl-CH2), 29.3 (octyl-CH2), 26.1 (octyl-CH2), 23.7 (acetate-CH3),
14.1 (octyl-CH3); JC-1,H-1¼177.0 Hz. HRMS (ESI) calcd for (MþNa)
C22H31NO5þNa: 412.2099, found 412.2093.
4.16. Cyclohexyl N-acetyl-2,3-aziridino-5-O-benzoyl-2,3-
dideoxy-b-D-ribofuranoside (27b)
The compound was isolated after chromatography (hex-
aneseEtOAc, 4:1) as a colorless oil. Rf 0.37 (hexaneseEtOAc, 3:1); 1H
NMR (500 MHz, CDCl3, dH) 8.12e8.03 (m, 2H), 7.62e7.55 (m, 1H),
7.51e7.46 (m, 2H), 5.33 (s, 1H, H-1), 4.40e4.60 (m, 3H, H-4, H-5),
3.70e3.64 (m, 1H), 3.44 (d, 1H, J¼3.5 Hz, H-2), 3.33 (d, 1H, J¼4.0 Hz,
H-3), 2.08 (s, 3H, acetate CH3), 1.98e1.17 (m, 10H, cyclohexyl CH2);
13C NMR (125.7 MHz, CDCl3, dC) 179.3 (C]O), 166.1 (C]O), 133.2
(AreC), 129.7 (AreC), 129.6 (AreC), 128.4 (AreC), 99.1 (C-1), 78.2
(cyclohexyl-CH), 74.3 (C-4), 65.0 (C-5), 42.7 (C-2), 41.0 (C-3), 33.2
(cyclohexyl CH2), 32.1 (cyclohexyl CH2), 29.6 (cyclohexyl CH2), 29.4
(cyclohexyl CH2), 24.1 (acetate CH3), 24.1 (cyclohexyl CH2); JC-1,H-
4.13. Methyl 5-O-(N-acetyl-2,3-aziridino-5-O-benzoyl-2,3-
dideoxy-a-D-ribofuranosyl)-2,3-anhydro-a-D-lyxofuranoside
(26
a)
The compound was isolated after chromatography (3:1, hex-
aneseEtOAc) as white solid: Rf 0.19 (3:2, hexaneseEtOAc); 1H
NMR (500 MHz, CDCl3, dH) 8.09e8.01 (m, 2H, Ar), 7.65e7.52 (m,
1H, Ar), 7.51e7.40 (m, 2H, Ar), 5.43 (d, 1H, J¼1.5 Hz, H-10), 4.93
(s, 1H, H-1), 4.76 (dd, 1H, J¼4.0, 4.0 Hz, H-40), 4.55 (dd, 1H, J¼3.5,
12.0 Hz, H-50), 4.42 (dd, 1H, J¼4.0, 12.0 Hz, H-50), 4.25 (dd, 1H,
J¼5.5, 10.0 Hz, H-5), 3.96 (dd, 1H, J¼5.0, 10.0 Hz, H-5), 3.82e3.76
(m, 2H, H-3, H-4), 3.65 (d, 1H, J¼3.5 Hz, H-2), 3.48 (dd, 1H, J¼1.5,
4.0 Hz, H-20), 3.41 (s, 3H,OCH3), 3.34 (d, 1H, J¼4.0 Hz, H-30), 2.06
(s, 3H, acetate CH3);13 C NMR (125.7 MHz, CDCl3, dC) 180.6 (C]O),
166.1 (C]O), 133.4 (AreC), 129.4 (AreC), 128.5 (AreC), 102.7 (azi-
C-1), 102.1 (epo-C-1), 74.9 (C-40), 74.5 (C-4), 67.3 (C-5), 64.8 (C-50),
56.3 (C-2), 55.5 (C-3), 42.5 (C-20), 40.5 (C-20), 24.0 (OCH3); JC-1,H-
¼175.1 Hz. HRMS (ESI) calcd for (MþNa) C20H25NO5þNa: 382.1629,
1
found 382.1623.
4.17. tert-Butyl N-acetyl-2,3-aziridino-5-O-benzoyl-2,3-
dideoxy-a-D-ribofuranoside (30a)
The compound was isolated after chromatography (3:1, hex-
aneseEtOAc) as a colorless oil: Rf 0.26 (2:1, hexaneseEtOAc); 1H
NMR (500 MHz, CDCl3, dH) 8.06e8.03 (m, 2H, Ar), 7.61e7.58 (m, 1H,
Ar), 7.53e7.47 (m, 2H, Ar), 5.52 (d, 1H, J¼1.0 Hz, H-1), 4.74 (dd, 1H,
J¼4.5, 4.5 Hz, H-4), 4.55 (dd, 1H, J¼4.5, 12.0 Hz, H-5), 4.40 (dd, 1H,
J¼4.5, 12.0 Hz, H-5), 3.29 (dd, 1H, J¼1.5, 4.0 Hz, H-2), 3.23 (d, 1H,
J¼4.0 Hz, H-3), 2.24 (s, 3H, acetate CH3), 1.23 (s, 9H, tert-butyl CH3);
13C NMR (125.7 MHz, CDCl3, dC) 181.0 (C]O), 166.1 (C]O), 133.4
(AreC), 129.6 (AreC), 129.6 (AreC), 128.5 (AreC), 96.8 (C-1), 75.8
(OC(CH3)3), 73.8 (C-4), 65.1 (C-5), 43.3 (C-2), 39.3 (C-3), 29.7
(C(CH3)3), 28.4 (C(CH3)3), 24.2 (acetate CH3); JC-1,H-1¼168.6 Hz.
HRMS (ESI) calcd for (MþNa) C18H23NO5þNa: 356.1473, found
356.1468.
¼169.1 Hz. HRMS (ESI) calcd for (MþNa) C20H23NO8þNa:
1
428.1321, found 428.1316.
4.14. Methyl 5-O-(N-acetyl-2,3-aziridino-5-O-benzoyl-2,3-
dideoxy-b-D-ribofuranosyl)-2,3-anhydro-b-D-lyxofuranoside
(26
b)
The compound was isolated after chromatography (3:1, hex-
aneseEtOAc) as white solid: Rf 0.22 (3:2, hexaneseEtOAc); 1H NMR
(500 MHz, CDCl3, dH) 8.06e8.04 (m, 2H, Ar), 7.66e7.63 (m, 1H, Ar),

4284
M.F. Ahmed, T.L. Lowary / Tetrahedron 69 (2013) 4276e4284
4.18. tert-Butyl N-acetyl-2,3-aziridino-5-O-benzoyl-2,3-
dideoxy- -ribofuranoside (30
spectral data for all new compounds. Supplementary data related
to this article can be found online at http://dx.doi.org/10.1016/
j.tet.2013.03.074.
b-D
b)
The compound was isolated after chromatography (3:1, hex-
aneseEtOAc) as a colorless oil: Rf 0.31 (2:1, hexaneseEtOAc); 1H
NMR (500 MHz, CDCl3, dH) 8.07e8.02 (m, 2H, Ar), 7.60e7.58 (m, 1H,
Ar), 7.53e7.47 (m, 2H, Ar), 5.47 (s, 1H, H-1), 4.55e4.44 (m, 3H, H-4,
2H-5), 3.45 (d, 1H, J¼4.0 Hz, H-2), 3.24 (d, 1H, J¼4.0 Hz, H-3), 2.15 (s,
3H, acetate CH3), 1.28 (s, 9H, tert-butyl CH3); 13C NMR (125.7 MHz,
CDCl3, dC) 181.0 (C]O), 166.1 (C]O), 133.2 (AreC), 129.8 (AreC),
129.7 (AreC), 128.4 (AreC), 95.5 (C-1), 75.8 (OC(CH3)3), 74.3 (C-4),
65.1 (C-5), 43.1 (C-2), 41.4 (C-3), 29.7 (C(CH3)3), 28.8 (C(CH3)3), 23.7
(acetate CH3); JC-1,H-1¼174.5 Hz. HRMS (ESI) calcd for (MþNa)
C18H23NO5þNa: 356.1473, found 356.1468.
References and notes
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The compound was isolated after chromatography (hex-
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1H NMR (500 MHz, CDCl3, dH) 8.12e8.03 (m, 2H, Ar), 7.62e7.52 (m,
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J¼4.0 Hz, H-3), 2.18 (br s, 3H), 1.90e1.75 (m, 6H, adamantyl CH2),
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1.55e1.65 (m, 6H, adamantyl CH2); 13C NMR (125.7 MHz, CDCl3, dC
)
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181.0 (C]O),166.1 (C]O),133.3 (AreC),129.7 (AreC),129.6 (AreC),
128.5 (AreC), 95.2 (C-1), 75.0 (C-4), 73.7 (adamantyl CO), 65.1 (C-5),
43.4 (C-2), 42.2 (adamantyl CH), 39.4 (C-3), 36.2 (adamantyl CH),
30.6 (adamantyl CH), 24.3 (CH3); JC-1,H-1¼167.4 Hz. HRMS (ESI) calcd
for (MþNa) C24H29NO5þNa: 434.1942, found 434.1936.
ꢁ
ꢁ
ꢂ
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4.20. 1-Adamantyl N-acetyl-2,3-aziridino-5-O-benzoyl-2,3-di-
deoxy-b-D-ribofuranoside (31b)
The compound was isolated after chromatography (hex-
aneseEtOAc, 3:1) as a colorless oil. Rf 0.24 (hexaneseEtOAc, 2:1); 1H
NMR (500 MHz, CDCl3, dH) 8.12e8.03 (m, 2H, Ar), 7.62e7.52 (m, 1H,
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This work was supported by the Natural Sciences and Engi-
neering Research Council of Canada. We thank Dr. Robert McDonald
(University of Alberta, Department of Chemistry, X-ray Crystallog-
raphy Laboratory) for obtaining the X-ray structure of 13 and for
assistance in generating Fig. 3.
Supplementary data
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These data include additional experimental details on the
attempted preparation of 4 from 13 and 1H and 13C NMR