1,3-Dipolar cycloaddition between N-benzyl-C-glycosyl nitrones and methyl acrylate en route to glycosyl pyrrolidines

Article abstract of DOI:10.1016/j.tetasy.2003.08.027

1,3-Dipolar cycloaddition reactions between three N-benzyl-C-glycosyl nitrones and methyl acrylate afforded key intermediates for the synthesis of glycosyl pyrrolidines. The best result was obtained with a D-galactose derived nitrone which afforded only one isomer in quantitative yield. Absolute configurations were assigned by applying the Kakisawa's rule and X-ray diffraction methods.

Full text of DOI:10.1016/j.tetasy.2003.08.027

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 14 (2003) 3731–3743
1,3-Dipolar cycloaddition between N-benzyl-C-glycosyl nitrones
and methyl acrylate en route to glycosyl pyrrolidines
Pedro Merino,* Santiago Franco, Francisco L. Merchan, Pilar Romero, Tomas Tejero and
Santiago Uriel
Departamento de Qu´ımica Orga´nica, ICMA, Facultad de Ciencias, Universidad de Zaragoza-CSIC, E-50009 Zaragoza,
Aragon, Spain
Received 28 July 2003; accepted 26 August 2003
Abstract—1,3-Dipolar cycloaddition reactions between three N-benzyl-C-glycosyl nitrones and methyl acrylate afforded key
intermediates for the synthesis of glycosyl pyrrolidines. The best result was obtained with a
D-galactose derived nitrone which
afforded only one isomer in quantitative yield. Absolute configurations were assigned by applying the Kakisawa’s rule and X-ray
diffraction methods.
© 2003 Elsevier Ltd. All rights reserved.
1. Introduction
instance, imino disaccharides linked by glycosidic
bonds extended with additional carbon atoms have
been prepared.4 The synthesis of nitrogen5 and sulfur6
containing links between the sugar and imino sugar
moieties have also been reported. Among the non-
hydrolyzable linkages, the all-carbon link leading to
imino-C-disaccharides7 (Fig. 1, X=−(CH2)n-, n=0, 1,
2) is considered the closest in structure to natural
sequences.8 The first example of imino-C-disaccharides
was reported by Johnson et al.9 In this regard, the
Vogel group pioneered the elaboration of flexible
methodologies for the preparation of imino-C-disac-
charides from the so-called ‘naked sugars’.10 Recently,
other research groups have reported some approaches
starting from natural sugars.11
The chemistry of imino disaccharides1 has become of
great interest in recent years because they can be pow-
erful glycosidase inhibitors, thus having an enormous
potential as bactericidal or as antidiabetes agents.2 A
number of synthetic routes have been developed to
various imino disaccharides, including MDL25,637,2b in
which one of the sugar moieties has been replaced by a
piperidine ring.3
The glycosidic linkage can also be replaced by different
sequences of atoms and the imino sugar can be either a
piperidine or a pyrrolidine ring (Fig. 1, o=1, 2). For
In particular, Brandi and Goti et al. applied an elegant
strategy, based on cycloaddition chemistry, to the syn-
thesis of imino-C-disaccharides in which a pyranose
ring is directly linked (X=0) to a hydroxylated pyrro-
lidine.12 The key step of this approach consisted of the
1,3-dipolar cycloaddition between a cyclic nitrone and a
glycal.
In this context and based on our previous experience,13
we envisioned that a pyrrolidinyl sugar system A might
be a valuable key intermediate for the preparation of
several carbohydrate mimics. Compound A would be
derived from isoxazolidine B which could be prepared
Figure 1. Imino disaccharides.
* Corresponding author. Tel.: +34-976-762075; fax: +34-976-762075;
e-mail: pmerino@unizar.es
0957-4166/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2003.08.027

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P. Merino et al. / Tetrahedron: Asymmetry 14 (2003) 3731–3743
3,5-disubstituted isoxazolidines 4 and 5. In all cases
purification by radial chromatography allowed the iso-
lation of pure compounds. Whereas the regioselectivity
of the reaction was very high (the corresponding 3,4-
regioisomers were not detected), both the endo/exo
selectivity and the diastereofacial induction (Re/Si )
were rather low (Table 1, entries 1–9). The cycloaddi-
tion proved to be not dependent of the reaction condi-
tions (solvent and temperature). Even the use of
microwaves (Table 1, entry 4) did not substantially
change the ratio of the products, although it did accel-
erate the reaction rate considerably. In general, a slight
trend towards endo adducts (as expected for cycloaddi-
tions with electron-poor alkenes) and Re attacks was
observed. On the other hand, pyranosyl nitrone 3 was
much more selective. Indeed, cycloaddition at ambient
temperatures afforded only one detectable (NMR)
adduct (Table 1, entry 11) which was identified as
Re-endo 6a. The obtained isoxazolidines were trans-
formed into the corresponding N-benzyl-3-hydroxy-2-
pyrrolidinones by treatment with Zn in acetic acid
(Scheme 2).13
Scheme 1.
through the cycloaddition between an N-benzyl-C-gly-
cosyl nitrone14 C and methyl acrylate (Scheme 1).15
Herein we report our results on the cycloaddition reac-
tion between C-furanosyl/C-pyranosyl nitrones C and
methyl acrylate, and the further elaboration of the
obtained glycosyl isoxazolidines into glycosyl pyrrolidi-
nes A.
Spectroscopic data and chemical behavior supported
the structural assignments made to adducts 4–6 given in
Table 1. The relative cis/trans configuration was
assigned by NOE experiments (Fig. 2). Thus, for trans-
compounds 4a–6a and 4d–6d, irradiation of H-3 only
produced a strong enhancement of H-4a (15–17%) and
irradiation of H-5 only produced enhancement of H-4b
(11–17%). In addition, irradiation of H-4a and H-4b in
the same experiment produced enhancements of H-3
(9–11%) and H-5 (8–12%). For cis-compounds 4b–6b
and 4c–6c, irradiation of H-4a produced enhancements
of both H-3 (5–17%) and H-5 (14–17%). Irradiation of
H-5 produced enhancement of H-4a (10–15%) and a
smaller enhancement of H-3 (5–6%). Irradiation of H-3
produced enhancement of H-4a (8–12%) and H-5 (5–
6%). The relative configuration between the isoxazo-
lidine ring and the sugar moiety could not be
2. Results and discussion
2.1. Cycloaddition reactions and synthesis of imino-C-
disaccharides
The nitrones 1–3 used in this study were easily prepared
from the corresponding aldehyde following our previ-
ously described procedure.16 Condensation of nitrones
1–3 with an excess of methyl acrylate under several
conditions afforded the corresponding mixtures of isox-
azolidines. In all cases the chemical yield of the reaction
was quantitative. The results of the reactions illustrated
in Scheme 2 are collected in Table 1.
It was found that furanosyl nitrones 1 and 2 reacted
with methyl acrylate to give mixtures of all possible
Scheme 2. Reagents and conditions: (i) Methyl acrylate. See Table 1; (ii) Zn/AcOH–H2O, 60°C, 5 h.

P. Merino et al. / Tetrahedron: Asymmetry 14 (2003) 3731–3743
3733
Table 1. Cycloaddition reactions between nitrones 1–3 and methyl acrylatea and further conversion to pyrroldinones 7–9
Entry
Nitrone
Solvent
Temp. (°C) Time (h)
Yield (%)b
Isoxazolidine a:b:c:dc
endo/exod
Re/Sie
Pyrrolidinone
1
2
3
4
5
6
7
8
1
1
1
1
1
1
2
2
2
3
3
3
Neat
Neat
Neat
Neat
CHCl3
Toluene
Neat
Neat
CHCl3
Neat
80
25
0.5
2
6
100
100
100
100
100
100
100
100
100
100
100
100
4
4
4
4
4
4
5
5
5
6
6
6
34:25:22:19 53:47
32:27:22:19 51:49
59:41
59:41
61:39
59:41
66:34
61:39
55:45
60:40
61:39
79:21
100:0
85:15
7
7
7
7
7
7
8
8
8
9
9
9
−18
33:28:21:18 51:49
35:24:22:19 54:46
41:25:18:16 57:43
34:27:24:15 49:51
36:19:21:24 60:40
34:26:20:20 54:46
39:22:20:19 58:42
MWf
0.1
72
72
0.5
2
90
0.5
4
25
25
80
25
25
80
25
25
9
10
11
12
74:5:11:10
100:0:0:0g
78:7:7:8
84:16
100:0
86:14
Neat
CHCl3
72
a The reaction was stopped when no more starting material was observed (TLC).
b All reactions showed quantitative yields calculated with respect to the isolated mixture of isoxazolidines.
c Measured by NMR in the crude mixture of the reaction.
d Referred to the a+d:b+c ratio.
e Referred to the a+b:c+d ratio.
f Carried out in a conventional oven at 700 W.
g Only one isomer could be detected by NMR noise-to-signal ratio.
determined by spectroscopic means and it was assigned
from further derivatives as discussed below.
N-Debenzylation was quantitatively achieved for com-
pounds 7a and 8a by reaction with lithium in liquid
ammonia (Scheme 3).
Scheme 3. Reagents and conditions: (i) Li/liquid NH3.
In the case of compound 8a the O-benzyl group was
Figure 2. Selected NOE observed for 4–6 (pobs given as
percent of pmax).
also eliminated and 11 was obtained. Compounds 10
and 11 can be considered immediate precursors of
glycosyl pyrrolidines. The pyranosyl pyrrolidinone 9a
was further converted, after N-debenzylation with
lithium in liquid ammonia into protected galactosyl
pyrrolidine 15 by sequential O- and N-protection and
reduction of the lactam moiety with LiEt3BH (Scheme
4). Compound 15 was obtained as a 3:1 mixture of
isomers which were identified by NMR (see Section 4).
successful application of Kakisawa’s rule, we need a
comparison between values corresponding to a pair of
isomers having an opposite configuration. As a result
we synthesized the corresponding Mosher esters derived
from (R)- and (S)-Mosher acids (Scheme 5). This
methodology is equivalent to that of preparing the
esters of racemic mixtures using an only enantiomeri-
cally pure Mosher acid. Condensation of the corre-
sponding alcohols with the acid chloride afforded pairs
of diastereomeric esters which were purified by radial
chromatography.
2.2. Determination of the absolute configuration
In order to determine the absolute configuration of the
new stereogenic centers we applied Kakisawa’s rule17
for inferring the orientation of the hydroxyl group at
C-3 in the pyrrolidinone rings. Since the relative cis/
trans-configuration had been previously assigned, it was
only necessary to prepare the corresponding Mosher
esters of compounds 7a, 7c, 8a, 8c, 9a and 9c. For a
Only in the case of compound 8c did we find that the
reaction did not work and the corresponding esters
1
could not be obtained. The H NMR spectra of the
esters were recorded and the differences in the chemical

3734
P. Merino et al. / Tetrahedron: Asymmetry 14 (2003) 3731–3743
ring could be determined independently of the other
asymmetric centers of the molecule. By defining Dla
and Dlb as indicated in Eqs. (1) and (2) (lSH4a and
lSH4b refers to the chemical shifts of (S)-MTPA esters,
and lRH4a and lRH4b refers to the chemical shifts of
(R)-MTPA esters), positive and negative values would
indicate (R) and (S)-configurations, respectively, at C-3
in the pyrrolidine ring.
Dla=lSH4a−lRH4a
Dlb=lSH4b−lRH4b
(1)
(2)
As indicated in Table 2 it was confirmed as an (R)-
configuration for compounds 7a, 7c, 8a, 9a and 9c thus
unequivocally ascertaining the absolute configuration
for the rest of isomers, too.
Scheme 4. Reagents and conditions: (i) Li/liquid NH3; (ii)
TBSCl, DMF, imidazole; (iii) Boc2O, DMPA, NEt3, CH2Cl2;
(iv) LiEt3BH, THF.
In addition, we were able to obtain a single crystal of
compound 9a suitable for carrying out an X-ray analy-
sis. This analysis18 (Fig. 3) further confirmed the
assigned configuration for that compound.
3. Conclusions
In conclusion, we have studied the 1,3-dipolar cycload-
dition between N-benzyl-C-glycosyl nitrones and
methyl acrylate as a novel route for the preparation of
glycosyl pyrrolidines. Of the three chiral non-racemic
nitrones used in this work, the furanosyl nitrones 1 and
2 showed little endo/exo and diastereofacial selectivities,
whereas the pyranosyl nitrone 3 was much more selec-
tive and only one isomer was obtained. The synthetic
utility of the methodology was addressed by preparing
the protected glycosyl pyrrolidine 15, consisting of a
Scheme 5. Reagents and conditions: (i) (+)-(R)-MTPA-Cl,
DCC, DMAP, CH2Cl2; (ii) (−)-(S)-MTPA-Cl, DCC, DMAP,
CH2Cl2.
D
-galactosyl unit directly linked to a 2,3-dihydroxy-
pyrrolidine. The complete protection of all functional
groups in 15 but leaving the free hydroxyl group at C-2
in the pyrrolidine ring, made this compound to be
considered as a useful building block for the construc-
tion of more complex structures by means of glycosila-
tion reactions. Further studies in connection to the
enhancement of the selectivities for furanosyl nitrones
and application to the synthesis of carbohydrate mimics
are the subject of ongoing investigations.
shift calculated. The data are collected in Table 2.
According to Kakisawa’s rule, the methylene group
(H4a and H4b) is selectively shielded by the phenyl
group when the two groups are located on the same
side of the plane containing H3 and the carbonyl group
(compounds 16a–e in Scheme 4). In this way the abso-
lute configuration (R or S) at the C-3 of the pyrrolidine
Table 2. Selected chemical shifts and differences for 16a–e and 17a–ea
MTPA-Cl
Ester
lH4a
Dla
lH4b
Dlb
Conf.
R
7a
7c
8a
9a
9c
R
S
R
S
R
S
R
S
R
S
16a
17a
16b
17b
16c
17c
16d
17d
16e
17e
2.63
2.64
2.37
2.40
2.58
2.60
2.60
2.63
2.52
2.54
+0.01
+0.03
+0.02
+0.03
+0.02
2.22
2.36
2.08
2.26
2.22
2.40
2.26
2.41
1.92
2.11
+0.14
+0.18
+0.18
+0.15
+0.19
R
R
R
R
a All reactions were carried out neat except for entry 6 which was carried out in toluene as a solvent.

P. Merino et al. / Tetrahedron: Asymmetry 14 (2003) 3731–3743
3735
4.1. 1,3-Dipolar cycloaddition of nitrones 1-3 with methyl
acrylate. General procedure
The corresponding nitrone 1–3 (2 mmol) was dissolved
in methyl acrylate (5.92 g, 80 mmol) and the resulting
solution stirred at reflux until no more nitrone was
observed (TLC). The reaction mixture was evaporated
to dryness and the residue analyzed by NMR to deter-
mine the diastereomeric ratio. Purification by radial
chromatography gave the pure adducts (eluent is given
in brackets).
4.1.1. 4-[(3R,5R)-2-Benzyl-5-(methoxycarbonyl)-3-isoxa-
zolidinyl]-2,3-O-isopropyliden-1-O-methyl-a- -lyxo-
D
tetrofuranose 4a. (Hexane/EtOAc, 80:20; Rf=0.30);
0.268 g (34%); oil; [h]2D5=+113 (c 1.21, CHCl3); IR
1
(wCꢀO) 1730 cm−1; H NMR (CDCl3, 55°C) l 1.23 (s,
3H, CH3), 1.32 (s, 3H, CH3), 2.71 (td, 1H, J=7.7, 12.9
Hz, H4b), 2.80 (ddd, 1H, J=3.1, 8.4, 12.9 Hz, H4a), 3.30
(s, 3H, OCH3), 3.76 (dt, 1H, J=3.1, 8.5 Hz, H3), 3.78
(s, 3H, OCH3), 3.85 (dd, 1H, J=3.3, 8.6 Hz, H4%), 3.96
(d, 1H, J=13.3 Hz, NCH2Ph), 4.23 (d, 1H, J=13.3 Hz,
NCH2Ph), 4.50 (d, 1H, J=5.8 Hz, H2%), 4.58 (t, 1H,
J=8.1 Hz, H5), 4.69 (dd, 1H, J=3.3, 5.8 Hz, H3%), 4.83
(s, 1H, H1%), 7.20–7.32 (m, 5H, ArH). 13C NMR
(CDCl3) l 24.7, 25.9, 35.3, 37.6, 52.1, 54.4, 62.4, 63.3,
79.7, 79.8, 85.2, 107.4, 112.2, 127.1, 128.1, 129.4, 137.7,
172.9. Anal. calcd for C20H27NO7: C, 61.06; H, 6.92; N,
3.56. Found: C, 61.30; H, 6.96; N, 3.70.
Figure 3. Perspective view (ORTEP) of 9a. Non-hydrogen
atoms are drawn as 50% thermal ellipsoids while hydrogens
are drawn at an arbitrary size. Only the atoms refined with
anisotropic thermal parameters are drawn with the principal
axes indicated; the isotropic atoms are represented as simple
circles.
4.1.2. 4-[(3R,5S)-2-Benzyl-5-(methoxycarbonyl)-3-isoxa-
zolidinyl]-2,3-O-isopropyliden-1-O-methyl-a- -lyxo-
D
tetrofuranose 4b. (Hexane/EtOAc, 80:20; Rf=0.28);
0.196 g (25%); oil; [h]2D5=+24 (c 0.12, CHCl3); IR (wCꢀO
)
1735 cm−1; 1H NMR (CDCl3, 55°C) l 1.21 (s, 3H,
CH3), 1.30 (s, 3H, CH3), 2.62 (ddd, 1H, J=3.4, 5.9,
12.9 Hz, H4b), 2.73 (ddd, 1H, J=7.8, 9.2, 12.9 Hz, H4a),
3.25 (s, 3H, OCH3), 3.65 (ddd, 1H, J=3.4, 7.8, 9.5 Hz,
H3), 3.72 (s, 3H, OCH3), 3.89 (dd, 1H, J=3.4, 9.5 Hz,
H4%), 3.97 (d, 1H, J=13.4 Hz, NCH2Ph), 4.02 (d, 1H,
J=13.4 Hz, NCH2Ph), 4.46 (d, 1H, J=5.9, H2%), 4.69
(dd, 1H, J=3.4, 5.9 Hz, H3%), 4.70 (dd, 1H, J=5.9, 9.2
Hz, H5), 4.78 (s, 1H, H1%), 7.15–7.45 (m, 5H, ArH). 13C
NMR (CDCl3) l 24.7, 25.9, 30.6, 35.5, 52.0, 54.0, 61.2,
62.5, 79.5, 80.0, 85.2, 107.0, 112.1, 127.2, 128.1, 129.3,
137.0, 171.5. Anal. calcd for C20H27NO7: C, 61.06; H,
6.92; N, 3.56. Found: C, 61.22; H, 6.85; N, 3.62.
4. Experimental
The reaction flasks and other glass equipment were
heated in an oven at 130°C overnight and assembled in
a stream of Ar. All reactions were monitored by TLC
on silica gel 60 F254; the position of the spots were
detected with 254 nm UV light or by spraying with one
of the following staining systems: 50% methanolic sul-
furic acid, 5% ethanolic phosphomolybdic acid and
iodine. Preparative centrifugally accelerated radial thin-
layer chromatography (radial chromatography) was
performed with a Chromatotron® model 7924 T (Har-
rison Research, Palo Alto, CA, USA) and with solvents
that were distilled prior to use; the rotors (1 or 2 mm
layer thickness) were coated with silica gel Merck grade
type 7749, TLC grade, with binder and fluorescence
indicator (Aldrich 34,644-6) and the eluting solvents
delivered by the pump at a flow-rate of 0.5–1.5 mL
min−1. Melting points are uncorrected. 1H and 13C
NMR spectra were recorded on a Varian Unity or on a
Bruker 300 instrument in CDCl3. Chemical shifts are
reported in ppm (l) relative to CHCl3 (l=7.26) in
CDCl3. Optical rotations were taken at 25°C on a
Perkin–Elmer 241 polarimeter. Elemental analyses were
performed on a Perkin–Elmer 240B microanalyzer.
4.1.3. 4-[(3S,5R)-2-Benzyl-5-(methoxycarbonyl)-3-isoxa-
zolidinyl]-2,3-O-isopropyliden-1-O-methyl-a- -lyxo-
D
tetrofuranose 4c. (Hexane/EtOAc, 80:20; Rf=0.21);
0.174 g (22%); oil; [h]2D5=−35 (c 0.75, CHCl3); IR (wCꢀO
)
1732 cm−1; 1H NMR (CDCl3, 55°C) l 1.27 (s, 3H,
CH3), 1.42 (s, 3H, CH3), 2.33 (ddd, 1H, J=5.3, 8.3,
13.1 Hz, H4b), 2.86 (ddd, 1H, J=8.3, 9.1, 13.1 Hz, H4a),
3.21 (q, 1H, J=8.3 Hz, H3), 3.26 (s, 3H, OCH3), 3.73
(s, 3H, OCH3), 3.94 (d, 1H, J=15.2 Hz, NCH2Ph), 4.00
(dd, 1H, J=3.5, 8.3 Hz, H4%), 4.51 (d, 1H, J=5.8 Hz,
H2%), 4.52 (d, 1H, J=15.2 Hz, NCH2Ph), 4.53 (dd, 1H,
J=5.3, 9.1 Hz, H5), 4.67 (dd, 1H, J=3.5, 5.8 Hz, H3%),
4.90 (s, 1H, H1%), 7.18–7.34 (m, 5H, ArH). 13C NMR
(CDCl3) l 24.9, 26.1, 35.8, 38.2, 52.3, 54.6, 60.7, 64.1,
80.9, 81.2, 84.5, 107.4, 112.6, 126.9, 128.1, 128.8, 137.6,
Nitrones 1, 2 and 3 were prepared from
D-ribose,
D
-glucose and
D
-galactose, respectively, as described.16

3736
P. Merino et al. / Tetrahedron: Asymmetry 14 (2003) 3731–3743
172.8. Anal. calcd for C20H27NO7: C, 61.06; H, 6.92; N,
3.56. Found: C, 60.99; H, 6.87; N, 3.51.
4.1.7. 4-[(3S,5R)-2-Benzyl-5-(methoxycarbonyl)-3-isoxa-
zolidinyl]-3-O-benzyl-1,2-O-isopropyliden-a- -xylo-tetro-
D
furanose 5c. (Hexane/Et2O, 60:40; Rf=0.15); 0.196 g
(21%); oil; [h]D25=−97 (c 0.70, CHCl3); IR (wCꢀO) 1728
cm−1; 1H NMR (CDCl3, 55°C) l 1.32 (s, 3H, CH3), 1.49
(s, 3H, CH3), 2.17 (ddd, 1H, J=5.0, 8.3, 12.6 Hz, H4b),
2.58 (ddd, 1H, J=8.3, 9.1, 12.6 Hz, H4a), 3.28 (q, 1H,
J=8.3 Hz, H3), 3.74 (s, 3H, OCH3), 3.89 (d, 1H,
J=15.1 Hz, NCH2Ph), 3.92 (d, 1H, J=3.3 Hz, H3%),
4.25 (dd, 1H, J=3.3, 8.6 Hz, H4%), 4.46 (d, 1H, J=11.6
Hz, OCH2Ph), 4.49 (dd, 1H, J=5.0, 9.1 Hz, H5), 4.56
(d, 1H, J=15.1 Hz, NCH2Ph), 4.61 (d, 1H, J=3.9 Hz,
H2%), 4.70 (d, 1H, J=11.6 Hz, OCH2Ph), 5.97 (d, 1H,
J=3.9 Hz, H1%), 7.20–7.50 (m, 10H, ArH). 13C NMR
(CDCl3) l 26.3, 26.8, 35.5, 52.2, 60.8, 64.2, 71.8, 74.0,
81.2, 81.8, 83.5, 105.6, 111.8, 126.8, 127.8, 128.0, 128.2,
128.4, 128.6, 137.1, 137.8, 172.8. Anal. calcd for
C26H31NO7: C, 66.51; H, 6.65; N, 2.98. Found: C,
66.69; H, 6.58; N, 3.09.
4.1.4. 4-[(3S,5S)-2-Benzyl-5-(methoxycarbonyl)-3-isoxa-
zolidinyl]-2,3-O-isopropyliden-1-O-methyl-a- -lyxo-
D
tetrofuranose 4d. (Hexane/EtOAc, 80:20; Rf=0.17);
0.150 g (19%); oil; [h]2D5=−168 (c 0.35, CHCl3); IR
1
(wCꢀO) 1730 cm−1; H NMR (CDCl3, 55°C) l 1.28 (s,
3H, CH3), 1.42 (s, 3H, CH3), 2.41 (td, 1H, J=8.9, 12.6
Hz, H4a), 2.71 (ddd, 1H, J=5.3, 7.4, 12.6 Hz, H4b), 3.32
(s, 3H, OCH3), 3.39 (q, 1H, J=8.1 Hz, H3), 3.74 (s, 3H,
OCH3), 3.99 (dd, 1H, J=3.6, 7.8 Hz, H4%), 4.08 (d, 1H,
J=14.3 Hz, NCH2Ph), 4.47 (d, 1H, J=14.3 Hz,
NCH2Ph), 4.50 (d, 1H, J=5.8 Hz, H2%), 4.51 (dd, 1H,
J=5.3, 8.9 Hz, H5), 4.66 (dd, 1H, J=3.6, 5.8 Hz, H3%),
4.92 (s, 1H, H1%), 7.18–7.34 (m, 5H, ArH). 13C NMR
(CDCl3) l 24.9, 26.1, 32.8, 36.5, 52.2, 53.7, 62.2, 64.0,
74.8, 80.7, 84.6, 107.3, 112.7, 127.0, 128.2, 129.1, 138.2,
172.6. Anal. calcd for C20H27NO7: C, 61.06; H, 6.92; N,
3.56. Found: C, 61.19; H, 7.04; N, 3.49.
4.1.8. 4-[(3S,5S)-2-Benzyl-5-(methoxycarbonyl)-3-isoxa-
zolidinyl]-3-O-benzyl-1,2-O-isopropyliden-a- -xylo-tetro-
D
4.1.5. 4-[(3R,5R)-2-Benzyl-5-(methoxycarbonyl)-3-isoxa-
furanose 5d. (Hexane/Et2O, 60:40; Rf=0.10); 0.226 g
zolidinyl]-3-O-benzyl-1,2-O-isopropyliden-a- -xylo-
D
(24%); white solid; mp 106–108°C; [h]2D5=−67 (c 0.95,
tetrofuranose 5a. (Hexane/Et2O, 60:40; Rf=0.29); 0.338
g (36%); oil; [h]D25=−21 (c 1.25, CHCl3); IR (wCꢀO) 1725
cm−1; 1H NMR (CDCl3, 55°C) l 1.29 (s, 3H, CH3), 1.47
(s, 3H, CH3), 2.73 (td, 1H, J=7.6, 13.1 Hz, H4b), 2.92
(ddd, 1H, J=1.7, 8.5, 13.1 Hz, H4a), 3.75 (d, 2H,
J=13.3 Hz, NCH2Ph), 3.76 (s, 3H, OCH3), 3.91 (m,
1H, H3), 4.07 (d, 1H, J=3.0 Hz, H3%), 4.10 (dd, 1H,
J=3.0, 9.1 Hz, H4%), 4.20 (d, 2H, J=13.3 Hz,
NCH2Ph), 4.30 (d, 1H, J=11.7 Hz, OCH2Ph), 4.49 (d,
1H, J=11.7 Hz, OCH2Ph), 4.54 (d, 1H, J=3.8 Hz,
H2%), 4.61 (t, 1H, J=8.4 Hz, H5), 5.88 (d, 1H, J=3.8
Hz, H1%), 7.15–7.38 (m, 10H, ArH). 13C NMR (CDCl3)
l 26.2, 26.8, 34.8, 52.4, 62.4, 63.0, 72.0, 77.2, 79.8, 81.7,
82.3, 105.0, 111.7, 127.3, 127.6, 127.9, 128.3, 128.5,
129.4, 137.5, 127.6, 173.2. Anal. calcd for C26H31NO7:
C, 66.51; H, 6.65; N, 2.98. Found: C, 66.36; H, 6.57; N,
2.95.
1
CHCl3); IR (wCꢀO) 1730 cm−1; H NMR (CDCl3, 55°C)
l 1.31 (s, 3H, CH3), 1.48 (s, 3H, CH3), 2.18 (td, 1H,
J=8.8, 12.4 Hz, H4a), 2.37 (ddd, 1H, J=4.8, 7.3, 12.4
Hz, H4b), 3.44 (dt, 1H, J=7.3, 8.8 Hz, H3), 3.71 (s, 3H,
OCH3), 3.87 (d, 1H, J=3.3 Hz, H3%), 4.03 (d, 1H,
J=14.1 Hz, NCH2Ph), 4.41 (d, 1H, J=14.1 Hz,
NCH2Ph), 4.20 (dd, 1H, J=3.3, 8.6 Hz, H4%), 4.42 (d,
1H, J=11.7 Hz, OCH2Ph), 4.44 (dd, 1H, J=4.8, 8.8
Hz, H5), 4.60 (d, 1H, J=3.9 Hz, H2%), 4.69 (d, 1H,
J=11.7 Hz, OCH2Ph), 5.96 (d, 1H, J=3.9 Hz, H1%),
7.17–7.43 (m, 10H, ArH). 13C NMR (CDCl3) l 26.3,
26.7, 36.1, 52.2, 62.4, 63.7, 71.8, 74.9, 81.2, 81.7, 82.9,
105.5, 111.8, 127.0, 128.0, 128.1, 128.2, 128.6, 129.1,
136.9, 138.2, 172.1. Anal. calcd for C26H31NO7: C,
66.51; H, 6.65; N, 2.98. Found: C, 66.61; H, 6.52; N,
2.92.
4.1.6. 4-[(3R,5S)-2-Benzyl-5-(methoxycarbonyl)-3-isoxa-
4.1.9. 5-[(3R,5R)-2-Benzyl-5-(methoxycarbonyl)-3-isoxa-
zolidinyl]-3-O-benzyl-1,2-O-isopropyliden-a-
D
-xylo-tetro-
zolidinyl]-1,2:3,4-di-O-isopropyliden-a- -galacto-pento-
D
furanose 5b. (Hexane/Et2O, 60:40; Rf=0.21); 0.178 g
(19%); oil; [h]D25=−4 (c 0.75, CHCl3); IR (wCꢀO) 1732
cm−1; 1H NMR (CDCl3, 55°C) l 1.27 (s, 3H, CH3), 1.46
(s, 3H, CH3), 2.67 (ddd, 1H, J=2.5, 5.6, 13.4 Hz, H4b),
2.76 (ddd, 1H, J=7.7, 9.8, 13.4 Hz, H4a), 3.71 (s, 3H,
OCH3), 3.75 (d, 1H, J=13.6 Hz, NCH2Ph), 3.78 (ddd,
1H, J=2.5, 7.7, 9.9 Hz, H3), 3.89 (d, 1H, J=13.6 Hz,
NCH2Ph), 4.09 (d, 1H, J=3.1 Hz, H3%), 4.23 (dd, 1H,
J=3.1, 9.9 Hz, H4%), 4.30 (d, 1H, J=11.7 Hz,
OCH2Ph), 4.50 (d, 1H, J=11.7 Hz, OCH2Ph), 4.52 (d,
1H, J=3.7 Hz, H2%), 4.72 (dd, 1H, J=5.6, 9.8 Hz, H5),
5.83 (d, 1H, J=3.7 Hz, H1%), 7.16–7.30 (m, 10H, ArH).
13C NMR (CDCl3) l 26.5, 26.8, 35.4, 52.3, 61.1, 62.1,
71.9, 75.3, 80.6, 81.7, 82.3, 104.8, 111.9, 127.5, 127.5,
127.8, 128.3, 128.4, 129.0, 136.8, 137.6, 171.5. Anal.
calcd for C26H31NO7: C, 66.51; H, 6.65; N, 2.98.
Found: C, 66.73; H, 6.79; N, 3.13.
pyranose 6a. (Hexane/Et2O, 60:40; Rf=0.41); 0.664 g
(74%); white solid; mp 117–119°C; [h]2D5=−82 (c 0.40,
1
CHCl3); IR (wCꢀO) 1730 cm−1; H NMR (CDCl3, 55°C)
l 1.23 (s, 3H, CH3), 1.31 (s, 6H, CH3), 1.47 (s, 3H,
CH3), 2.64 (ddd, 1H, J=7.0, 8.4, 13.0 Hz, H4b), 2.85
(ddd, 1H, J=1.8, 8.4, 13.0 Hz, H4a), 3.56 (dd, 1H,
J=1.3, 10.0 Hz, H5%), 3.67 (ddd, 1H, J=1.8, 7.0, 10.0
Hz, H3), 3.77 (s, 3H, OCH3), 3.87 (d, 1H, J=13.2 Hz,
NCH2Ph), 4.24 (d, 1H, J=13.2 Hz, NCH2Ph), 4.26
(dd, 1H, J=2.1, 4.9 Hz, H2%), 4.43 (dd, 1H, J=1.3, 8.1
Hz, H4%), 4.49 (t, 1H, J=8.4 Hz, H5), 4.52 (dd, 1H,
J=2.1, 8.1 Hz, H3%), 5.48 (d, 1H, J=4.9 Hz, H1%),
7.20–7.42 (m, 5H, ArH). 13C NMR (CDCl3) l 24.0,
24.9, 25.8, 26.2, 34.1, 52.1, 62.6, 64.1, 64.7, 67.1, 70.7,
70.8, 71.2, 96.6, 108.4, 108.7, 127.1, 128.1, 129.5, 137.6,
173.0. Anal. calcd for C23H31NO8: C, 61.46; H, 6.95; N,
3.12. Found: C, 61.55; H, 7.03; N, 3.00.

P. Merino et al. / Tetrahedron: Asymmetry 14 (2003) 3731–3743
3737
4.1.10. 5-[(3R,5S)-2-Benzyl-5-(methoxycarbonyl)-3-isox-
azolidinyl]-1,2:3,4-di-O-isopropyliden-a- -galacto-pento-
mL), water (10 mL) and Zn dust (0.200 g, 3.1 mmol);
the resulting solution was heated at 60°C for 5 h. After
cooling at ambient temperature, the reaction mixture
was filtered through a plug of Celite. The filtrate was
treated with a saturated aqueous solution of sodium
carbonate and the resulting mixture extracted with
CH2Cl2 (3×15 mL). The combined organic layers were
washed with brine, dried over magnesium sulfate and
evaporated to yield a residue which was purified by
radial chromatography.
D
pyranose 6b. (Hexane/Et2O, 60:40; Rf=0.35); 0.046 g
(5%); oil; [h]D25=−26 (c 0.40, CHCl3); IR (wCꢀO) 1738
cm−1; 1H NMR (CDCl3, 55°C) l 1.20 (s, 3H, CH3), 1.27
(s, 3H, CH3), 1.48 (s, 6H, CH3), 2.54 (ddd, 1H, J=2.8,
6.6, 13.2 Hz, H4b), 2.72 (ddd, 1H, J=8.2, 9.2, 13.2 Hz,
H4a), 3.54 (dt, 1H, J=2.8, 8.2 Hz, H3), 3.67 (d, 1H,
J=8.2, H5%), 3.70 (s, 3H, OCH3), 3.89 (d, 1H, J=13.1
Hz, NCH2Ph), 4.02 (d, 1H, J=13.1 Hz, NCH2Ph), 4.19
(dd, 1H, J=1.9, 4.9 Hz, H2%), 4.43 (bd, 1H, J=8.0 Hz,
H4%), 4.49 (dd, 1H, J=1.9, 8.0 Hz, H3%), 4.72 (dd, 1H,
J=6.6, 9.2 Hz, H5), 5.44 (d, 1H, J=4.9 Hz, H1%),
7.20–7.40 (m, 5H, ArH). 13C NMR (CDCl3) l 23.8,
24.6, 25.7, 25.8, 35.3, 52.0, 57.7, 61.2, 63.5, 68.6, 70.7,
70.8, 71.0, 96.3, 108.4, 109.3, 127.2, 128.1, 129.4, 136.9,
171.0. Anal. calcd for C23H31NO8: C, 61.46; H, 6.95; N,
3.12. Found: C, 61.32; H, 7.03; N, 3.21.
4.2.1.
4-[(3R,5R)-1-Benzyl-3-hydroxy-2-oxo-5-pyrro-
-lyxo-tetro-
lidinyl]-2,3-O-isopropyliden-1-O-methyl-a-
D
furanose 7a. (Et2O; Rf=0.31); 0.291 g (80%); white
solid; mp 136–138°C; [h]2D5=+88 (c 0.25, CHCl3); IR
(wCꢀO) 1680 cm−1; H NMR (CDCl3, 55°C) l 1.24 (s,
1
3H, CH3), 1.41 (s, 3H, CH3), 2.22 (td, 1H, J=5.4, 14.0
Hz, H4b), 2.49 (td, 1H, J=7.6, 14.0 Hz, H4a), 3.23 (s,
3H, OCH3), 3.79 (bs, 1H, OH), 3.83 (td, 1H, J=5.0,
7.6 Hz, H5), 4.02–4.04 (bs, 1H, H4%), 4.28 (d, 1H,
J=15.2 Hz, NCH2Ph), 4.33 (dd, 1H, J=5.4, 7.6 Hz,
H3), 4.46–4.50 (m, 2H, H2% and H3%), 4.87 (d, 1H,
J=15.2 Hz, NCH2Ph), 4.89 (s, 1H, H1%), 7.08–7.18 (m,
5H, ArH). 13C NMR (CDCl3) l 24.3, 25.7, 30.9, 45.3,
54.5, 54.8, 69.6, 78.0, 79.6, 85.3, 106.7, 112.8, 127.6,
127.7, 128.7, 136.6, 175.5. Anal. calcd for C19H25NO6:
C, 62.80; H, 6.93; N, 3.85. Found: C, 62.95; H, 6.97; N,
4.00.
4.1.11. 5-[(3S,5R)-2-Benzyl-5-(methoxycarbonyl)-3-isox-
azolidinyl]-1,2:3,4-di-O-isopropyliden-a- -galacto-pento-
D
pyranose 6c. (Hexane/Et2O, 60:40; Rf=0.19); 0.098 g
(11%); oil; [h]D25=−55 (c 0.90, CHCl3); IR (wCꢀO) 1736
cm−1; 1H NMR (CDCl3, 55°C) l 1.30 (s, 3H, CH3), 1.31
(s, 3H, CH3), 1.42 (s, 3H, CH3), 1.51 (s, 3H, CH3), 2.43
(ddd, 1H, J=5.5, 7.7, 12.5 Hz, H4b), 2.68 (ddd, 1H,
J=8.1, 8.8, 12.5 Hz, H4a), 3.20 (q, 1H, J=8.0 Hz, H3),
3.69 (s, 3H, OCH3), 3.88 (dd, 1H, J=1.8, 8.1 Hz, H5%),
3.90 (d, 1H, J=14.6 Hz, NCH2Ph), 4.23 (dd, 1H,
J=1.8, 7.9 Hz, H4%), 4.26 (dd, 1H, J=2.5, 5.0 Hz, H2%),
4.46 (d, 1H, J=14.6 Hz, NCH2Ph), 4.49 (dd, 1H,
J=5.5, 8.8 Hz, H5), 4.57 (dd, 1H, J=2.5, 7.9 Hz, H3%),
5.78 (d, 1H, J=5.0 Hz, H1%), 7.14–7.44 (m, 5H, ArH).
13C NMR (CDCl3) l 24.5, 25.1, 26.0, 26.0, 35.0, 52.2,
61.0, 64.1, 69.5, 70.3, 70.9, 72.3, 74.2, 96.3, 108.9, 109.4,
126.8, 127.9, 129.0, 137.8, 172.6. Anal. calcd for
C23H31NO8: C, 61.46; H, 6.95; N, 3.12. Found: C,
61.21; H, 7.08; N, 3.25.
4.2.2.
4-[(3S,5R)-1-Benzyl-3-hydroxy-2-oxo-5-pyrro-
lidinyl]-2,3-O-isopropyliden-1-O-methyl-a- -lyxo-tetro-
D
furanose 7b. (Et2O; Rf=0.20); 0.254 g (70%); oil;
[h]2D5=+79 (c 0.71, CHCl3); IR (wCꢀO) 1680 cm−1; H
1
NMR (CDCl3, 55°C) l 1.26 (s, 3H, CH3), 1.30 (s, 3H,
CH3), 2.03 (td, 1H, J=8.9, 13.6 Hz, H4b), 2.27 (ddd,
1H, J=1.6, 8.1, 13.6 Hz, H4a), 3.25 (s, 3H, OCH3), 3.70
(bs, 1H, OH), 3.76 (dt, 1H, J=1.6, 8.5 Hz, H5), 3.85
(dd, 1H, J=3.5, 8.5 Hz, H4%), 4.34 (d, 1H, J=14.3 Hz,
NCH2Ph), 4.50 (t, 1H, J=8.6 Hz, H3), 4.51 (d, 1H,
J=5.8 Hz, H2%), 4.66 (dd, 1H, J=3.5, 5.8 Hz, H3%), 4.93
(s, 1H, H1%), 5.09 (d, 1H, J=14.3 Hz, NCH2Ph), 7.20–
7.27 (m, 5H, ArH). 13C NMR (CDCl3) l 24.9, 26.0,
31.6, 46.3, 53.3, 54.8, 68.9, 80.4, 83.5, 84.3, 107.7, 112.9,
127.6, 128.6, 128.8, 136.3, 175.2. Anal. calcd for
C19H25NO6: C, 62.80; H, 6.93; N, 3.85. Found: C,
62.88; H, 6.89; N, 4.72.
4.1.12. 5-[(3S,5S)-2-Benzyl-5-(methoxycarbonyl)-3-isox-
azolidinyl]-1,2:3,4-di-O-isopropyliden-a- -galacto-pento-
D
pyranose 6d. (Hexane/Et2O, 60:40; Rf=0.16); 0.090 g
(10%); oil; [h]D25=−38 (c 1.25, CHCl3); IR (wCꢀO) 1734
cm−1; 1H NMR (CDCl3, 55°C) l 1.31 (s, 6H, CH3), 1.43
(s, 3H, CH3), 1.51 (s, 3H, CH3), 2.53 (td, 1H, J=8.8,
12.5 Hz, H4a), 2.61 (ddd, 1H, J=5.1, 7.3, 12.5 Hz, H4b),
3.34 (q, 1H, J=7.7 Hz, H3), 3.74 (s, 3H, OCH3), 3.86
(dd, 1H, J=1.8, 7.4 Hz, H5%), 4.06 (d, 1H, J=14.0 Hz,
NCH2Ph), 4.24 (dd, 1H, J=1.8, 8.1 Hz, H4%), 4.26 (dd,
1H, J=2.6, 4.8 Hz, H2%), 4.39 (d, 1H, J=14.0 Hz,
NCH2Ph), 4.52 (dd, 1H, J=5.1, 8.8 Hz, H5), 4.58 (dd,
1H, J=2.6, 8.1 Hz, H3%), 5.50 (d, 1H, J=4.8 Hz, H1%),
7.10–7.40 (m, 5H, ArH). 13C NMR (CDCl3) l 24.4,
25.0, 25.9, 26.1, 35.6, 51.9, 62.4, 64.4, 69.5, 70.7, 71.0,
72.1, 75.2, 96.3, 108.8, 109.5, 126.8, 128.0, 129.1, 138.4,
172.3. Anal. calcd for C23H31NO8: C, 61.46; H, 6.95; N,
3.12. Found: C, 61.64; H, 6.82; N, 3.23.
4.2.3.
4-[(3R,5S)-1-Benzyl-3-hydroxy-2-oxo-5-pyrro-
lidinyl]-2,3-O-isopropyliden-1-O-methyl-a- -lyxo-tetro-
D
furanose 7c. (Et2O; Rf=0.16); 0.285 g (78%); oil;
[h]2D5=+176 (c 0.62, CHCl3); IR (wCꢀO) 1690 cm−1; H
1
NMR (CDCl3, 55°C) l 1.25 (s, 3H, CH3), 1.29 (s, 3H,
CH3), 2.03 (td, 1H, J=8.5, 13.6 Hz, H4b), 2.26 (ddd,
1H, J=1.5, 8.5, 13.6 Hz, H4a), 3.24 (s, 3H, OCH3), 3.75
(dt, 1H, J=1.5, 8.5 Hz, H5), 3.84 (dd, 1H, J=3.3, 8.5
Hz, H4%), 4.15 (bs, 1H, OH), 4.32 (d, 1H, J=14.3 Hz,
NCH2Ph), 4.50 (d, 1H, J=5.9 Hz, H2%), 4.50 (t, 1H,
J=8.5 Hz, H3), 4.67 (dd, 1H, J=3.3, 5.9 Hz, H3%), 4.90
(s, 1H, H1%), 5.08 (d, 1H, J=14.3 Hz, NCH2Ph), 7.18–
7.35 (m, 5H, ArH). 13C NMR (CDCl3) l 24.9, 25.9,
31.6, 46.3, 53.4, 54.8, 68.9, 80.4, 83.5, 84.3, 107.7, 112.9,
127.5, 128.6, 128.8, 136.3, 175.5. Anal. calcd for
C19H25NO6: C, 62.80; H, 6.93; N, 3.85. Found: C,
62.92; H, 6.86; N, 3.75.
4.2. Reduction of ixoazolidines 4–6. Synthesis of pyrro-
lidin-2-ones 7–9. General procedure
A solution of the corresponding isoxazolidine (1 mmol)
in THF (10 mL) was treated with glacial acetic acid (20

3738
P. Merino et al. / Tetrahedron: Asymmetry 14 (2003) 3731–3743
4.2.4.
4-[(3S,5S)-1-Benzyl-3-hydroxy-2-oxo-5-pyrro-
-lyxo-tetro-
OH), 3.85 (ddd, 1H, J=3.6, 7.2, 9.4 Hz, H5), 3.91 (d,
lidinyl]-2,3-O-isopropyliden-1-O-methyl-a-
D
1H, J=3.3 Hz, H3%), 4.08 (dd, 1H, J=3.3, 9.4 Hz, H4%),
4.36 and 5.05 (2d, 2H, J=14.6 Hz, NCH2Ph), 4.39 (d,
1H, J=11.8 Hz, OCH2Ph), 4.42 (t, 1H, J=8.6 Hz, H3),
4.56 (d, 1H, J=3.8 Hz, H2%), 4.63 (d, 1H, J=11.8 Hz,
OCH2Ph), 5.98 (d, 1H, J=3.8 Hz, H1%), 7.16–7.36 (m,
10H, ArH). 13C NMR (CDCl3) l 26.2, 26.7, 31.5, 46.2,
53.4, 68.7, 71.8, 81.1, 82.5, 84.0, 105.6, 111.9, 127.3,
128.0, 128.3, 128.5, 128.5, 128.6, 134.2, 136.1, 174.9.
Anal. calcd for C25H29NO6: C, 68.32; H, 6.65; N, 3.19.
Found: C, 68.56; H, 6.44; N, 3.11.
furanose 7d. (Et2O; Rf=0.32); 0.327 g (90%); white
solid; mp 76–78°C; [h]2D5=+46 (c 0.30, CHCl3); IR
(wCꢀO) 1685 cm−1; H NMR (CDCl3, 55°C) l 1.26 (s,
1
3H, CH3), 1.33 (s, 3H, CH3), 1.72 (td, 1H, J=6.7, 13.4
Hz, H4b), 2.61 (ddd, 1H, J=7.2, 8.3, 13.4 Hz, H4a), 3.14
(s, 3H, OCH3), 3.74 (dt, 1H, J=6.7, 8.3 Hz, H5), 3.95
(dd, 1H, J=3.5, 8.3 Hz, H4%), 4.34 (t, 1H, J=7.1 Hz,
H3), 4.48 (d, 1H, J=5.8 Hz, H2%), 4.49 (d, 1H, J=14.4
Hz, NCH2Ph), 4.71 (dd, 1H, J=3.5, 5.8 Hz, H3%), 4.91
(s, 1H, H1%), 4.98 (d, 1H, J=14.4 Hz, NCH2Ph), 4.60
(bs, 1H, OH), 7.07–7.19 (m, 5H, ArH). 13C NMR
(CDCl3) l 24.9, 26.0, 30.8, 45.9, 54.7, 54.8, 69.3, 80.5,
84.8 (2C), 107.9, 112.7, 127.3, 128.3, 128.4, 137.1, 175.7.
Anal. calcd for C19H25NO6: C, 62.80; H, 6.93; N, 3.85.
Found: C, 62.72; H, 6.95; N, 3.91.
4.2.8.
4-[(3S,5S)-1-Benzyl-3-hydroxy-2-oxo-5-pyrro-
-xylo-tetro-
lidinyl]-3-O-benzyl-1,2-O-isopropyliden-a-
D
furanose 8d. (Et2O; Rf=0.29); 0.365 g (83%); white
solid; mp 197–199°C; [h]2D5=−29 (c 0.81, CHCl3); IR
(wCꢀO) 1700 cm−1; H NMR (CDCl3, 55°C) l 1.29 (s,
1
3H, CH3), 1.34 (s, 3H, CH3), 1.52 (td, 1H, J=7.6, 13.1
Hz, H4b), 2.00 (bs, 1H, OH), 2.42 (td, 1H, J=7.6, 13.1
Hz, H4a), 3.77 (q, 1H, J=8.1 Hz, H5), 3.95 (d, 1H,
J=3.1 Hz, H3%), 4.11 (dd, 1H, J=3.1, 8.3 Hz, H4%), 4.31
(t, 1H, J=7.6 Hz, H3), 4.40 (d, 1H, J=11.4, OCH2Ph),
4.53 (d, 1H, J=14.5 Hz, NCH2Ph), 4.56 (d, 1H, J=3.8
Hz, H2%), 4.63 (d, 1H, J=11.4, OCH2Ph), 4.88 (d, 1H,
J=14.5 Hz, NCH2Ph), 5.99 (d, 1H, J=3.8 Hz, H1%),
7.06–7.43 (m, 10H, ArH). 13C NMR (CDCl3) l 26.3,
26.6, 29.7, 45.5, 54.7, 69.0, 71.9, 80.5, 82.7, 84.0, 105.6,
111.9, 127.2, 128.0, 128.3, 128.5, 128.6, 128.8, 136.6,
137.2, 175.4. Anal. calcd for C25H29NO6: C, 68.32; H,
6.65; N, 3.19. Found: C, 68.21; H, 6.77; N, 3.07.
4.2.5.
4-[(3R,5R)-1-Benzyl-3-hydroxy-2-oxo-5-pyrro-
-xylo-tetro-
lidinyl]-3-O-benzyl-1,2-O-isopropyliden-a-
D
furanose 8a. (Et2O; Rf=0.27); 0.334 g (76%); white
solid; mp 152–154°C; [h]2D5=−22 (c 0.88, CHCl3); IR
(wCꢀO) 1700 cm−1; H NMR (CDCl3, 55°C) l 1.26 (s,
1
3H, CH3), 1.32 (s, 3H, CH3), 2.23 (td, 1H, J=5.6, 14.0
Hz, H4b), 2.42 (td, 1H, J=7.8, 14.0 Hz, H4a), 3.75 (ddd,
1H, J=3.4, 5.6, 7.4 Hz, H5), 3.80 (d, 1H, J=3.4 Hz,
H3%), 4.09 (bs, 1H, OH), 4.19 (d, 1H, J=15.6 Hz,
NCH2Ph), 4.25–4.30 (m, 1H, H3), 4.29 (t, 1H, J=3.4
Hz, H4%), 4.32 (d, 1H, J=11.7 Hz, OCH2Ph), 4.56 (d,
1H, J=3.8 Hz, H2%), 4.58 (d, 1H, J=11.7 Hz,
OCH2Ph), 4.77 (d, 1H, J=15.6 Hz, NCH2Ph), 5.90 (d,
1H, J=3.8 Hz, H1%), 7.06–7.30 (m, 10H, ArH). 13C
NMR (CDCl3) l 26.3, 26.8, 30.8, 45.0, 54.6, 69.4, 71.8,
77.8, 82.1, 82.7, 104.6, 111.9, 127.4, 127.5 (2C), 128.0,
128.4, 128.7, 136.3, 137.0, 175.0. Anal. calcd for
C25H29NO6: C, 68.32; H, 6.65; N, 3.19. Found: C,
68.42; H, 6.72; N, 3.23.
4.2.9.
lidinyl]-1,2:3,4-di-O-isopropyliden-a-
ranose 9a. (Et2O; Rf=0.40); 0.394 g (90%); white solid;
mp 124–126°C; [h]2D5=+47 (c 0.40, CHCl3); IR (wCꢀO
5-[(3R,5R)-1-Benzyl-3-hydroxy-2-oxo-5-pyrro-
D
-galacto-pentopy-
)
1688 cm−1; 1H NMR (CDCl3, 55°C) l 1.29 (s, 3H,
CH3), 1.33 (s, 3H, CH3), 1.43 (s, 3H, CH3), 1.57 (s, 3H,
CH3), 2.25–2.42 (m, 2H, H4b and H4a), 3.27 (bs, 1H,
OH), 3.62–3.67 (m, 1H, H5), 4.00 (d, 1H, J=15.3 Hz,
NCH2Ph), 4.01 (bs, 1H, H5%), 4.10 (dd, 1H, J=1.6, 8.0
Hz, H4%), 4.25 (dd, 1H, J=5.8, 6.9 Hz, H3), 4.31 (dd,
1H, J=2.0, 5.1 Hz, H2%), 4.59 (dd, 1H, J=2.0, 8.0 Hz,
H3%), 5.20 (d, 1H, J=15.3 Hz, NCH2Ph), 5.57 (d, 1H,
J=5.1 Hz, H1%), 7.14–7.35 (m, 5H, ArH). 13C NMR
(CDCl3) l 24.1, 24.7, 25.8, 26.1, 30.2, 44.1, 55.6, 65.0,
70.0, 70.5, 71.2, 71.6, 96.7, 108.6, 109.5, 127.6, 127.8,
128.8, 136.2, 175.1. Anal. calcd for C22H29NO7: C,
62.99; H, 6.97; N, 3.34. Found: C, 62.85; H, 7.15; N,
3.37.
4.2.6.
4-[(3S,5R)-1-Benzyl-3-hydroxy-2-oxo-5-pyrro-
lidinyl]-3-O-benzyl-1,2-O-isopropyliden-a- -xylo-tetro-
D
furanose 8b. (Et2O; Rf=0.35); 0.365 g (83%); oil;
[h]2D5=−86 (c 0.64, CHCl3); IR (wCꢀO) 1695 cm−1; H
1
NMR (CDCl3, 55°C) l 1.29 (s, 3H, CH3), 1.36 (s, 3H,
CH3), 1.79 (td, 1H, J=9.0, 13.0 Hz, H4b), 2.84 (ddd,
1H, J=1.0, 8.3, 13.0 Hz, H4a), 3.64 (bs, 1H, OH), 3.71
(bdd, 1H, J=3.3, 9.0, H5), 3.80 (d, 1H, J=3.3 Hz, H3%),
4.15 (d, 1H, J=15.2 Hz, NCH2Ph), 4.23 (t, 1H, J=3.3
Hz, H4%), 4.38 (d, 1H, J=11.9, OCH2Ph), 4.59 (t, 1H,
J=8.8 Hz, H3), 4.59 (d, 1H, J=3.8 Hz, H2%), 4.63 (d,
1H, J=11.9, OCH2Ph), 4.82 (d, 1H, J=15.2 Hz,
NCH2Ph), 5.91 (d, 1H, J=3.8 Hz, H1%), 7.10–7.35 (m,
10H, ArH). 13C NMR (CDCl3) l 26.2, 26.8, 31.3, 45.3,
54.6, 69.1, 71.8, 78.5, 82.1, 82.8, 104.9, 111.9, 127.4,
127.6, 127.7, 128.1, 128.6, 128.8, 135.9, 137.0, 176.0.
Anal. calcd for C25H29NO6: C, 68.32; H, 6.65; N, 3.19.
Found: C, 68.14; H, 6.73; N, 3.27.
4.2.10.
5-[(3S,5R)-1-Benzyl-3-hydroxy-2-oxo-5-pyrro-
lidinyl]-1,2:3,4-di-O-isopropyliden-a- -galacto-pentopy-
D
ranose 9b. (Et2O; Rf=0.39); 0.381 g (91%); oil;
[h]2D5=−115 (c 0.35, CHCl3); IR (wCꢀO) 1695 cm−1; H
1
NMR (CDCl3, 55°C) l 1.24 (s, 3H, CH3), 1.32 (s, 3H,
CH3), 1.44 (s, 3H, CH3), 1.52 (s, 3H, CH3), 1.85 (td,
1H, J=8.5, 13.1 Hz, H4b), 2.86 (dd, 1H, J=8.8, 13.1
Hz, H4a), 3.00 (bs, 1H, OH), 3.58 (dd, 1H, J=4.3, 8.2
Hz, H5), 3.76 (dd, 1H, J=1.8, 4.3 Hz, H5%), 3.92 (d, 1H,
J=14.9 Hz, NCH2Ph), 4.10 (dd, 1H, J=1.8, 8.0 Hz,
H4%), 4.31 (dd, 1H, J=2.3, 5.1 Hz, H2%), 4.52 (t, 1H,
J=9.0 Hz, H3), 4.59 (dd, 1H, J=2.3, 8.0 Hz, H3%), 5.18
(d, 1H, J=14.9 Hz, NCH2Ph), 5.51 (d, 1H, J=5.1 Hz,
4.2.7.
4-[(3R,5S)-1-Benzyl-3-hydroxy-2-oxo-5-pyrro-
lidinyl]-3-O-benzyl-1,2-O-isopropyliden-a- -xylo-tetro-
D
furanose 8c. (Et2O; Rf=0.25); 0.356 g (81%); oil;
[h]2D5=+24 (c 0.34, CHCl3); IR (wCꢀO) 1686 cm−1; H
1
NMR (CDCl3, 55°C) l 1.32 (s, 3H, CH3), 1.45 (s, 3H,
CH3), 1.86–1.93 (m, 2H, H4a and H4b), 3.70 (bs, 1H,

P. Merino et al. / Tetrahedron: Asymmetry 14 (2003) 3731–3743
3739
H1%), 7.18–7.34 (m, 5H, ArH). 13C NMR (CDCl3) l
24.1, 24.7, 27.8, 26.3, 31.0, 44.8, 54.5, 65.9, 69.0, 70.4,
71.0, 71.5, 96.4, 108.4, 109.5, 127.8, 128.1, 128.8, 135.7,
176.0. Anal. calcd for C22H29NO7: C, 62.99; H, 6.97; N,
3.34. Found: C, 63.20; H, 6.87; N, 3.45.
4.3.1. 4-[(3R,5R)-3-Hydroxy-2-oxo-5-pyrrolidinyl]-2,3-
O-isopropyliden-1-O-methyl-a- -lyxo-tetrofuranose 10.
D
(EtOAc; Rf=0.17); 0.265 g (97%); oil; [h]2D5=+18 (c
1
0.32, CHCl3); IR (wCꢀO) 1705 cm−1; H NMR (CDCl3,
55°C) l 1.29 (s, 3H, CH3), 1.43 (s, 3H, CH3), 1.65 (bs,
1H, OH), 1.98 (td, 1H, J=6.6, 13.4 Hz, H4b), 2.71 (td,
1H, J=7.2, 13.4 Hz, H4a), 3.29 (s, 3H, OCH3), 3.79–
3.86 (m, 2H, H5 and H4%), 4.31 (t, 1H, J=6.9 Hz, H3),
4.56 (d, 1H, J=5.9, H2%), 4.72 (dd, 1H, J=3.4, 5.9 Hz,
H3%), 4.90 (s, 1H, H1%), 6.53 (bs, 1H, NH). 13C NMR
(CDCl3) l 24.6, 25.9, 34.2, 50.5, 54.6, 69.2, 79.3, 83.0,
84.9, 107.0, 112.9, 177.9. Anal. calcd for C12H19NO6: C,
52.74; H, 7.01; N, 5.13. Found: C, 52.58; H, 6.97; N,
5.08.
4.2.11.
lidinyl]-1,2:3,4-di-O-isopropyliden-a-
ranose 9c. (Et2O; Rf=0.24); 0.369
5-[(3R,5S)-1-Benzyl-3-hydroxy-2-oxo-5-pyrro-
-galacto-pentopy-
(88%); oil;
D
g
1
[h]2D5=+35 (c 0.45, CHCl3); IR (wCꢀO) 1686 cm−1; H
NMR (CDCl3, 55°C) l 1.27 (s, 3H, CH3), 1.31 (s, 3H,
CH3), 1.32 (s, 3H, CH3), 1.45 (s, 3H, CH3), 1.92 (td,
1H, J=8.8, 13.9 Hz, H4b), 2.34 (ddd, 1H, J=1.1, 7.9,
13.9 Hz, H4a), 3.41 (bs, 1H, OH), 3.69–3.71 (m, 2H, H5%
and H5), 4.17 (dd, 1H, J=1.0, 7.8 Hz, H4%), 4.29 (d, 1H,
J=14.4 Hz, NCH2Ph), 4.30 (dd, 1H, J=2.6, 5.0 Hz,
H2%), 4.45 (t, 1H, J=8.5 Hz, H3), 4.56 (dd, 1H, J=2.6,
7.8 Hz, H3%), 5.12 (d, 1H, J=14.4 Hz, NCH2Ph), 5.56
(d, 1H, J=5.0 Hz, H1%), 7.19–7.32 (m, 5H, ArH). 13C
NMR (CDCl3) l 24.6, 24.8, 25.8, 26.1, 31.0, 46.6, 53.3,
68.9, 70.1, 70.8, 70.9, 71.2, 96.3, 108.9, 109.8, 127.5,
128.5, 128.7, 136.2, 175.2. Anal. calcd for C22H29NO7:
C, 62.99; H, 6.97; N, 3.34. Found: C, 63.27; H, 6.95; N,
3.28.
4.3.2. 4-[(3R,5R)-3-Hydroxy-2-oxo-5-pyrrolidinyl]-3-O-
benzyl-1,2-O-isopropyliden-a- -xylo-tetrofuranose 11.
D
(EtOAc/MeOH, 95:5; Rf=0.29); 0.234 g (90%); oil;
1
[h]2D5=+53 (c 0.75, CHCl3); IR (wCꢀO) 1710 cm−1; H
NMR (CDCl3, 55°C) l 1.25 (s, 3H, CH3), 1.31 (s, 3H,
CH3), 2.17–2.36 (m, 1H, H4b), 2.57–2.71 (m, 2H, H4a,
OH), 3.56–3.68 (m, 2H, H5 and H4%), 3.94–3.96 (m, 2H,
H3%, OH), 4.22 (bs, 1H, H3), 4.54 (d, 1H, J=3.6 Hz,
H2%), 5.70 (bs, 1H, NH), 5.93 (d, 1H, J=3.6 Hz, H1%).
13C NMR (CDCl3) l 26.1, 26.8, 29.7, 53.0, 67.1, 74.0,
83.2, 85.7, 105.2, 111.7, 180.0. Anal. calcd for
C11H17NO6: C, 50.96; H, 6.61; N, 5.40. Found: C,
51.28; H, 6.50; N, 5.30.
4.2.12.
5-[(3S,5S)-1-Benzyl-3-hydroxy-2-oxo-5-pyrro-
lidinyl]-1,2:3,4-di-O-isopropyliden-a- -galacto-pentopy-
D
ranose 9d. (Et2O; Rf=0.50); 0.370 g (88%); oil;
4.3.3. 5-[(3R,5R)-3-Hydroxy-2-oxo-5-pyrrolidinyl]-1,2:
[h]2D5=−10 (c 1.02, CHCl3); IR (wCꢀO) 1702 cm−1; H
3,4-di-O-isopropyliden-a-
D
-galacto-pentopyranose
12.
1
NMR (CDCl3, 55°C) l 1.30 (s, 3H, CH3), 1.34 (s, 6H,
CH3), 1.51 (s, 3H, CH3), 1.72 (td, 1H, J=7.4, 13.0 Hz,
H4b), 2.53 (ddd, 1H, J=6.7, 8.0, 13.0 Hz, H4a), 3.24 (bs,
1H, OH), 3.70 (q, 1H, J=7.6 Hz, H5), 3.86 (dd, 1H,
J=1.7, 8.0 Hz, H5%), 4.27 (dd, 1H, J=1.7, 7.9 Hz, H4%),
4.27 (t, 1H, J=7.0 Hz, H3), 4.31 (dd, 1H, J=2.6, 5.0
Hz, H2%), 4.49 (d, 1H, J=14.5 Hz, NCH2Ph), 4.59 (dd,
1H, J=2.6, 7.9 Hz, H3%), 5.08 (d, 1H, J=14.5 Hz,
NCH2Ph), 5.57 (d, 1H, J=5.0 Hz, H1%), 7.15–7.35 (m,
5H, ArH). 13C NMR (CDCl3) l 24.5, 24.9, 25.8, 25.9,
30.7, 45.2, 54.2, 69.4, 70.0, 70.8, 71.0, 72.1, 96.4, 109.0,
109.6, 127.2, 128.5, 128.7, 137.1, 175.4. Anal. calcd for
C22H29NO7: C, 62.99; H, 6.97; N, 3.34. Found: C,
62.78; H, 6.82; N, 3.41.
(EtOAc; Rf=0.22); 0.316 g (96%); white solid; mp
112–114°C; [h]D25=−29 (c 0.65, CHCl3); IR (wCꢀO) 1712
cm−1; 1H NMR (CDCl3, 55°C) l 1.31 (s, 3H, CH3), 1.34
(s, 3H, CH3), 1.43 (s, 3H, CH3), 1.51 (s, 3H, CH3), 2.00
(ddd, 1H, J=4.7, 6.2, 13.7 Hz, H4b), 2.62 (ddd, 1H,
J=6.4, 7.8, 13.7 Hz, H4a), 2.69 (bs, 1H, OH), 3.68–3.73
(m, 2H, H5 and H5%), 4.23 (dd, 1H, J=6.2, 7.8 Hz, H3),
4.26 (dd, 1H, J=1.4, 7.9, H4%), 4.33 (dd, 1H, J=2.6, 5.0
Hz, H2%), 4.63 (dd, 1H J=2.6, 7.9 Hz, H3%), 5.51 (d, 1H,
J=5.0 Hz, H1%), 5.69 (bs, 1H, NH). 13C NMR (CDCl3)
l 24.5, 25.0, 25.9 (2C), 33.7, 38.2, 51.3, 69.3, 70.3, 70.7,
70.9, 96.2, 109.0, 109.8, 177.6. Anal. calcd for
C15H23NO7: C, 54.70; H, 7.04; N, 4.25. Found: C,
54.87; H, 6.94; N, 4.32.
4.3. N-Debenzylation of pyrrolidinones. General
procedure
4.4. 5-[(3R,5R)-3-(tert-Butyldimethylsiloxy)-2-oxo-5-
pyrrolidinyl]-1,2:3,4-di-O-isopropyliden-a- -galacto-pento-
D
pyranose 13
To a solution of lithium (75 mg, 3 mmol) in liquid
ammonia (10 mL) cooled to −40°C was added dropwise
a solution of the corresponding N-benzyl-2-pyrrolidi-
none (0.75 mmol) in THF (3 mL). The mixture was
stirred for 2 h and then treated with solid ammonium
chloride until the solution became colourless. The
ammonia was allowed to evaporate at ambient temper-
ature after which water (5 mL) was added. The aqueous
solution was extracted with dichloromethane (3×10 ml),
dried over MgSO4 and evaporated under reduced pres-
sure. The residue was filtered through a short pad of
silica gel and eluted with ethyl acetate. Evaporation of
the solvent afforded the crude product which was
purified by radial chromatography.
A solution of 12 (0.165 g, 0.5 mmol) in DMF (5 mL)
was treated with imidazol (0.189 g) and tert-
butyldimethylsilyl chloride (0.113 g, 0.75 mmol). The
resulting solution was stirred at 70°C until no more
starting material was observed by TLC (ca. 1 h).
Methanol (5 mL) and water (20 mL) were added and
the resulting mixture extracted with EtOAc (3×25 mL).
The organic layers were combined, dried over magne-
sium sulfate and evaporated under reduced pressure to
give the crude material which was purified by radial
chormatography (hexane/Et2O, 40:60; Rf=0.21) to
afford pure 13 (0.182 g, 82%) as an oil; [h]2D5=−52 (c
1
0.15, CHCl3); IR (wCꢀO) 1715 cm−1; H NMR (CDCl3,

3740
P. Merino et al. / Tetrahedron: Asymmetry 14 (2003) 3731–3743
55°C) l 0.00 (s, 3H, SiCH3), 0.05 (s, 3H, SiCH3), 0.83
(s, 9H, Si(CH3)3), 1.24 (s, 3H, CH3), 1.29 (s, 3H, CH3),
1.36 (s, 3H, CH3), 1.44 (s, 3H, CH3), 1.76 (td, 1H,
J=6.9, 13.3 Hz, H4b), 2.52 (ddd, 1H, J=6.9, 8.0, 13.3
Hz, H4a), 3.52 (dd, 1H, J=1.4, 8.8 Hz, H5%), 3.61 (td,
1H, J=6.9, 8.8 Hz, H5), 4.18 (t, 1H, J=7.6 Hz, H3),
4.22 (dd, 1H, J=2.2, 5.0 Hz, H2%), 4.37 (dd, 1H, J=1.4,
7.9 Hz, H4%), 4.52 (dd, 1H, J=2.2, 7.9 Hz, H3%), 5.42 (d,
1H, J=5.0 Hz, H1%), 5.60 (bs, 1H, NH). 13C NMR
(CDCl3) l −5.0, −4.6, 18.3, 24.5, 24.9, 25.8, 25.9, 26.2,
38.2, 50.6, 70.1, 70.4, 70.7, 70.8, 71.7, 96.2, 108.8, 109.7,
176.0. Anal. calcd for C21H37NO7Si: C, 56.86; H, 8.41;
N, 3.16. Found: C, 57.18; H, 8.35; N, 3.10.
revealed that it was formed by a 3:1 mixture of epimers
at C-2%. The signals of each isomer could be identified
from the spectrum of the mixture.
1
Major isomer: H NMR (CDCl3, 55°C) l 0.09 (s, 3H,
SiCH3), 0.10 (s, 3H, SiCH3), 0.90 (s, 9H, Si(CH3)3), 1.28
(s, 3H, CH3), 1.31 (s, 3H, CH3), 1.41 (s, 3H, CH3), 1.45
(s, 9H, C(CH3)3), 1.47 (s, 3H, CH3), 2.12–2.30 (m, 2H,
H4b and H4a), 2.98 (bs, 1H, OH), 3.84–4.01 (m, 2H, H2,
H3 and H5), 4.19–4.28 (m, 3H, H2%, H4% and H5%), 4.56
(dd, 1H, J=2.3, 7.8 Hz, H3%), 5.54 (d, 1H, J=5.1 Hz,
H1%). 13C NMR (CDCl3) l −4.8 (2C), 18.4, 24.3, 25.0,
25.7, 25.8, 25.8, 28.4, 38.2, 56.0, 66.3, 70.9, 71.3, 71.9,
72.2, 80.3 (2C), 96.6, 108.9, 109.2, 153.9.
4.5. 5-[(3R,5R)-1-(tert-Butoxycarbonyl)-3-(tert-
butyldimethylsiloxy)-2-oxo-5-pyrrolidinyl]-1,2:3,4-di-O-
1
Minor isomer: H NMR (CDCl3, 55°C) l 0.16 (s, 3H,
isopropyliden-a- -galacto-pentopyranose 14
D
SiCH3), 0.21 (s, 3H, SiCH3), 0.92 (s, 9H, Si(CH3)3), 1.27
(s, 3H, CH3), 1.30 (s, 3H, CH3), 1.41 (s, 3H, CH3), 1.45
(s, 9H, (CH3)3), 1.48 (s, 3H, CH3), 1.80 (bs, 1H, OH),
2.12–2.30 (m, 2H, H4b and H4a), 3.84–4.01 (m, 2H, H2,
H3, H5), 4.19–4.28 (m, 3H, H2%, H4%, H5%), 4.53 (dd, 1H,
J=2.3, 6.3 Hz, H3%), 5.46 (d, 1H, J=5.0 Hz, H1%). 13C
NMR (CDCl3) l −4.5 (2C), 18.0, 24.4, 25.1, 25.9, 26.0,
26.1, 28.4, 42.8, 57.0, 66.8, 70.8, 71.3, 71.4, 72.7, 80.6,
80.8, 96.6, 108.4, 109.1, 154.3.
A solution of 13 (0.177 g, 0.4 mmol) in CH2Cl2 (15 ml)
was treated with Boc2O (0.105 g, 0.48 mmol), Et3N (61
mg, 0.6 mmol) and DMAP (7.2 mg, 0.06 mmol). The
reaction mixture was stirred at ambient temperature for
18 h, at which time 1N KHSO4 (10 mL) was added.
The organic layer was separated, washed with water
(1×15 ml) and brine (1×15 ml), dried over magnesium
sulfate and evaporated. The residue was purified by
radial chromatography (hexane/Et2O, 40:60; Rf=0.32)
to give pure 14 (0.194 g, 89%) as an oil; [h]2D5=−22 (c
4.7. Synthesis of Mosher esters. General procedure
1
0.10, CHCl3); IR (wCꢀO) 1710 cm−1; H NMR (CDCl3,
55°C) l 0.08 (s, 3H, SiCH3), 0.11 (s, 3H, SiCH3), 0.88
(s, 9H, Si(CH3)3), 1.26 (s, 3H, CH3), 1.29 (s, 3H, CH3),
1.40 (s, 3H, CH3), 1.43 (s, 3H, CH3), 1.50 (s, 9H,
C(CH3)3), 2.31 (ddd, 1H, J=8.4, 9.3, 13.6 Hz, H4b),
2.38 (ddd, 1H, J=7.8, 9.3, 13.6 Hz, H4a), 4.11 (dt, 1H,
J=1.2, 8.0 Hz, H5), 4.22 (t, 1H, J=9.3 Hz, H3), 4.24
(dd, 1H, J=2.3, 5.1 Hz, H2%), 4.27 (dd, 1H, J=2.3, 7.9
Hz, H4%), 4.38 (bs, 1H, H5%), 4.56 (dd, 1H, J=2.3, 7.9
Hz, H3%), 5.50 (d, 1H, J=5.1 Hz, H1%). 13C NMR
(CDCl3) l −5.1, −4.5, 18.1, 24.3, 24.8, 25.7, 26.0, 27.6,
28.1, 38.1, 55.0, 65.1, 70.5, 70.7, 71.4, 72.6, 83.0, 96.6,
108.4, 109.2, 151.2, 172.3. Anal. calcd for C26H45NO9Si:
C, 57.43; H, 8.34; N, 2.58. Found: C, 57.61; H, 8.29; N,
2.63.
To a solution of the corresponding pyrrolidin-2-one
(0.1 mmol) in CH2Cl2 (2 mL) was added the corre-
sponding MTPA chloride (0.12 mmol), DCC (31 mg,
0.15 mmol) and DMAP (6 mg, 0.01 mmol). The result-
ing solution was stirred at ambient temperature for 12
h at which time the reaction mixture was treated with 1
M HCl (1 mL). The organic layer was separated and
washed with a saturated aqueous solution of NaHCO3.
The organic layer was separated, dried over magnesium
sulfate, filtered and evaporated under reduced pressure.
The residue was purified by radial chromatography to
afford the pure Mosher esters.
4.7.1. 4-{(3R,5R)-1-Benzyl-3-[(1R)-1-methoxy-1-phenyl-
1-(trifluoromethyl)acetoxy]-2-oxo-5-pyrrolidinyl}-2,3-O-
4.6. 5-[(3R,5R)-1-(tert-Butoxycarbonyl)-3-(tert-butyl-
dimethylsiloxy)-2-hydroxy-5-pyrrolidinyl]-1,2:3,4-di-O-
isopropyliden-1-O-methyl-a-
D
-lyxo-tetrofuranose
16a.
isopropyliden-a-
D
-galacto-pentopyranose 15 (mixture of
(Hexane/Et2O; Rf=0.22); 53 mg (92%); oil; [h]2D5=+26
epimers at C-2%)
1
(c 0.50, CHCl3); H NMR (CDCl3, 55°C) l 1.23 (s, 3H,
CH3), 1.25 (s, 3H, CH3), 2.22 (td, 1H, J=5.7, 14.0 Hz,
H4b), 2.63 (ddd, 1H, J=7.1, 8.8, 14.0 Hz, H4a), 3.14 (s,
3H, OCH3), 3.64 (s, 3H, OCH3), 3.89 (td, 1H, J=5.3,
7.1 Hz, H5), 3.94 (dd, 1H, J=3.3, 5.1 Hz, H4%), 4.28 (d,
1H, J=15.2 Hz, NCH2Ph), 4.40 (dd, 1H, J=3.3, 5.1
Hz, H3%), 4.45 (d, 1H, J=5.9 Hz, H2%), 4.70 (s, 1H, H1%),
4.91 (d, 1H, J=15.2 Hz, NCH2Ph), 5.70 (dd, 1H,
J=5.9, 8.8 Hz, H3), 7.20–7.40 (m, 8H, ArH), 7.40–7.45
(m, 1H, ArH), 7.63–7.68 (m, 1H, ArH). 13C NMR
(CDCl3) l 24.4, 25.7, 29.7, 34.0, 45.4, 54.3, 54.8, 55.6,
71.7, 78.0, 79.4, 85.3, 106.6, 112.8, 121.3, 127.6, 127.7,
127.7, 128.5, 128.8, 129.7, 132.0, 136.2, 166.1, 170.4.
Anal. calcd for C29H32F3NO8: C, 60.10; H, 5.57; N,
2.42. Found: C, 60.30; H, 5.49; N, 2.33.
To a cooled (−78°C) solution of 14 (0.181 g, 0.33
mmol) in THF (10 mL) was added dropwise a solution
of LiEt3BH (0.67 mL of a 1 M solution in hexanes, 0.67
mmol). The resulting solution was stirred at −78°C for
1 h at which time the reaction was quenched with water
(0.5 mL) and allowed to warm to room temperature.
The reaction mixture was diluted with EtOAc (10 mL)
and brine (15 mL). The organic layer was separated,
and the aqueous layer extracted with EtOAc (3×15
mL). The combined organic extracts were washed with
brine, dried over magnesium sulfate, filtered and evapo-
rated. The residue was purified by radial chromatogra-
phy (hexane/Et2O, 20:80; Rf=0.30) to give 15 (0.134 g,
74%) as an oil. The NMR analysis of this product

P. Merino et al. / Tetrahedron: Asymmetry 14 (2003) 3731–3743
3741
4.7.5. 5-[(3R,5S)-1-Benzyl-3-[(1R)-1-methoxy-1-phenyl-
1-(trifluoromethyl)acetoxy]-2-oxo-5-pyrrolidinyl]-1,2:3,4-
4.7.2. 4-{(3R,5S)-1-Benzyl-3-[(1R)-1-methoxy-1-phenyl-
1-(trifluoromethyl)acetoxy]-2-oxo-5-pyrrolidinyl}-2,3-O-
isopropyliden-1-O-methyl-a-
D
-lyxo-tetrofuranose
16b.
di-O-isopropyliden-a-
D
-galacto-pentopyranose
16e.
(Hexane/Et2O, 60:40; Rf=0.22); 56 mg (97%); oil;
(Hexane/Et2O, 60:40; Rf=0.17); 59 mg (93%); oil;
1
[h]2D5=+69 (c 0.72, CHCl3); H NMR (CDCl3, 55°C) l
1
[h]2D5=+5 (c 0.50, CHCl3); H NMR (CDCl3, 55°C) l
1.25 (s, 3H, CH3), 1.29 (s, 3H, CH3), 2.08 (td, 1H,
J=8.6, 14.0 Hz, H4b), 2.37 (ddd, 1H, J=2.1, 8.6, 14.0
Hz, H4a), 3.26 (s, 3H, OCH3), 3.67 (s, 3H, OCH3), 3.81
(dt, 1H, J=2.1, 8.6 Hz, H5), 3.91 (dd, 1H, J=3.6, 8.6
Hz, H4%), 4.38 (d, 1H, J=14.3 Hz, NCH2Ph), 4.52 (d,
1H, J=6.0 Hz, H2%), 4.67 (dd, 1H, J=3.6, 6.0 Hz, H3%),
4.94 (s, 1H, H1%), 5.07 (d, 1H, J=14.3 Hz, NCH2Ph),
5.81 (t, 1H, J=8.6 Hz, H3), 7.20–7.95 (m, 10, ArH).
13C NMR (CDCl3) l 24.8, 25.8, 29.4, 34.0, 46.4, 53.6,
54.9, 55.8, 71.5, 80.2, 83.1, 84.3, 107.7, 113.0, 121.3,
127.4, 127.6, 128.6, 128.7, 128.8, 129.7, 132.1, 136.1,
166.1, 169.4. Anal. calcd for C29H32F3NO8: C, 60.10; H,
5.57; N, 2.42. Found: C, 59.91; H, 5.68; N, 2.48.
1.27 (s, 3H, CH3), 1.32 (s, 3H, CH3), 1.35 (s, 3H, CH3),
1.49 (s, 3H, CH3), 1.92 (td, 1H. J=8.4, 13.6 Hz, H4b),
2.52 (ddd, 1H, J=1.8, 8.4, 13.6 Hz, H4a), 3.66 (s, 3H,
OCH3), 3.77 (dt, 1H, J=1.8, 8.4 Hz, H5), 3.79 (dd, 1H,
J=1.8, 8.4 Hz, H5%), 4.11 (dd, 1H, J=1.8, 8.1 Hz, H4%),
4.28 (d, 1H, J=14.7 Hz, NCH2Ph), 4.31 (dd, 1H,
J=2.6, 5.1 Hz, H2%), 4.56 (dd, 1H, J=2.6, 8.1 Hz, H3%),
5.08 (d, 1H, J=14.7 Hz, NCH2Ph), 5.54 (d, 1H, J=5.1
Hz, H1%), 5.80 (t, 1H, J=8.4 Hz, H3), 7.20–7.24 (m, 5H,
ArH), 7.36–7.46 (m, 3H, ArH), 7.56–7.62 (m, 2H,
ArH). 13C NMR (CDCl3) l 24.4, 24.8, 25.8, 26.2, 29.7,
46.3, 54.0, 55.5, 64.7, 69.7, 70.2, 70.8, 72.5, 85.6, 96.3,
109.0, 109.9, 123.7, 127.7, 127.8, 128.5, 128.6, 128.7,
129.8, 131.6, 135.9, 166.0, 169.6. Anal. calcd for
C32H36F3NO9: C, 60.47; H, 5.71; N, 2.20. Found: C,
60.69; H, 5.82; N,2.29.
4.7.3. 4-[(3R,5R)-1-Benzyl-3-[(1R)-1-methoxy-1-phenyl-
1-(trifluoromethyl)acetoxy]-2-oxo-5-pyrrolidinyl]-3-O-
benzyl-1,2-O-isopropyliden-a- -xylo-tetrofuranose 16c.
D
4.7.6. 4-{(3R,5R)-1-Benzyl-3-[(1S)-1-methoxy-1-phenyl-
1-(trifluoromethyl)acetoxy]-2-oxo-5-pyrrolidinyl}-2,3-O-
(Hexane/Et2O, 60:40; Rf=0.20); 61 mg (93%); oil;
1
[h]2D5=−9 (c 0.91, CHCl3); H NMR (CDCl3, 55°C) l
isopropyliden-1-O-methyl-a-
D
-lyxo-tetrofuranose
17a.
1.26 (s, 3H, CH3), 1.32 (s, 3H, CH3), 2.22 (td, 1H,
J=7.4, 14.3 Hz, H4b), 2.58 (ddd, 1H, J=7.4, 9.0, 14.3
Hz, H4a), 3.65 (s, 3H, OCH3), 3.72 (d, 1H, J=3.6 Hz,
H3%), 3.83 (dt, 1H, J=3.6, 7.4 Hz, H5), 4.20 (d, 1H,
J=15.5 Hz, NCH2Ph), 4.25 (t, 1H, J=3.6 Hz, H4%),
4.30 (d, 1H, J=11.7 Hz, OCH2Ph), 4.50 (d, 1H, J=3.6
Hz, H2%), 4.55 (d, 1H, J=11.7 Hz, OCH2Ph), 4.84 (d,
1H, J=15.5 Hz, NCH2Ph), 5.69 (dd, 1H, J=7.4, 9.0
Hz, H3), 5.72 (d, 1H, J=3.6 Hz, H1%), 7.10–7.46 (m,
13H, ArH), 7.60–7.70 (m, 2H, ArH). 13C NMR
(CDCl3) l 26.2, 26.7, 29.7, 45.2, 53.8, 55.7, 71.5, 71.6,
77.2, 77.6, 81.7, 82.3, 104.4, 111.7, 127.4, 127.5, 127.7,
128.2, 128.4, 128.6, 128.8, 129.6, 132.1, 135.7, 136.6,
166.2, 169.7. Anal. calcd for C35H36F3NO8: C, 64.11; H,
5.53; N, 2.14. Found: C, 63.86; H, 5.61; N, 2.02.
(Hexane/Et2O, 60:40; Rf=0.13); 55 mg (95%); oil;
1
[h]2D5=−4 (c 0.35, CHCl3); H NMR (CDCl3, 55°C) l
1.23 (s, 6H, CH3), 2.36 (td, 1H, J=5.7, 14.6 Hz, H4b),
2.64 (td, 1H, J=7.7, 14.6 Hz, H4a), 3.18 (s, 3H, OCH3),
3.56 (s, 3H, OCH3), 3.89 (td, 1H, J=5.6, 7.1 Hz, H5),
3.97 (dd, 1H, J=3.1, 5.3 Hz, H4%), 4.27 (d, 1H, J=15.6
Hz, NCH2Ph), 4.39 (dd, 1H, J=3.1, 6.0 Hz, H3%), 4.47
(d, 1H, J=6.0 Hz, H2%), 4.82 (s, 1H, H1%), 4.88 (d, 1H,
J=15.6 Hz, NCH2Ph), 5.62 (dd, 1H, J=5.7, 7.7 Hz,
H3), 7.20–7.36 (m, 5H, ArH), 7.37–7.40 (m, 3H, ArH),
7.58–7.62 (m, 2H, ArH). 13C NMR (CDCl3) l 24.3,
25.6, 29.7, 33.9, 45.4, 54.2, 54.8, 62.5, 72.1, 78.0, 79.4,
85.3, 106.6, 112.7, 125.1, 127.7, 127.8 (2C), 128.4, 128.7,
129.7, 131.7, 136.2, 165.9, 169.8. Anal. calcd for
C29H32F3NO8: C, 60.10; H, 5.57; N, 2.42. Found: C,
60.32; H, 5.65; N, 2.36.
4.7.4. 5-[(3R,5R)-1-Benzyl-3-[(1R)-1-methoxy-1-phenyl-
1-(trifluoromethyl)acetoxy]-2-oxo-5-pyrrolidinyl]-1,2:3,4-
4.7.7. 4-{(3R,5S)-1-Benzyl-3-[(1S)-1-methoxy-1-phenyl-
1-(trifluoromethyl)acetoxy]-2-oxo-5-pyrrolidinyl}-2,3-O-
di-O-isopropyliden-a-
D
-galacto-pentopyranose
16d.
isopropyliden-1-O-methyl-a-
D
-lyxo-tetrofuranose
17b.
(Hexane/Et2O, 60:40; Rf=0.24); 62 mg (98%); white
1
solid; mp 167–169°C; [h]2D5=−24 (c 0.55, CHCl3); H
(Hexane/Et2O, 60:40; Rf=0.16); 54 mg (94%); oil;
1
[h]2D5=+74 (c 0.33, CHCl3); H NMR (CDCl3, 55°C) l
NMR (CDCl3, 55°C) l 1.25 (s, 3H, CH3), 1.32 (s, 3H,
CH3), 1.36 (s, 3H, CH3), 1.54 (s, 3H, CH3), 2.26 (td,
1H, J=7.2, 14.3 Hz, H4b), 2.60 (ddd, 1H, J=7.8, 9.0,
14.3 Hz, H4a), 3.65 (s, 3H, OCH3), 3.71 (dt, 1H, J=2.3,
7.3 Hz, H5), 3.95–4.05 (m, 2H, H4% and H5%), 4.02 (d,
1H, J=15.5 Hz, NCH2Ph), 4.26 (dd, 1H, J=1.8, 5.3
Hz, H2%), 4.53 (dd, 1H, J=1.8, 7.9, H3%), 5.23 (d, 1H,
J=15.5 Hz, NCH2Ph), 5.43 (d, 1H, J=5.3, H1%), 5.62
(dd, 1H, J=7.2, 7.8 Hz, H3), 7.14–7.42 (m, 8H, ArH),
7.60–7.78 (m, 2H, ArH). 13C NMR (CDCl3) l 24.0,
24.5, 25.5, 26.2, 26.8, 44.1, 55.1, 55.5, 63.9, 70.4, 71.4,
71.6, 71.7, 89.6, 96.6, 108.1, 109.4, 121.3, 127.5, 127.7,
127.8, 128.2, 128.9, 129.4, 132.3, 135.8, 166.2, 169.6.
Anal. calcd for C32H36F3NO9: C, 60.47; H, 5.71; N,
2.20. Found: C, 60.54; H, 5.79; N, 2.34.
1.25 (s, 6H, CH3), 2.26 (td, 1H, J=8.1, 14.0 Hz, H4b),
2.40 (ddd, 1H, J=2.4, 8.6, 14.0 Hz, H4a), 3.26 (s, 3H,
OCH3), 3.51 (s, 3H, CH3), 3.86 (dt, 1H, J=2.4, 8.5 Hz,
H5), 3.91 (dd, 1H, J=3.1, 9.2 Hz, H4%), 4.36 (d, 1H,
J=14.3 Hz, NCH2Ph), 4.52 (d, 1H, J=6.0 Hz, H2%),
4.67 (dd, 1H, J=3.1, 6.0 Hz, H3%), 4.95 (s, 1H, H1%), 5.08
(d, 1H, J=14.3 Hz, NCH2Ph), 5.69 (t, 1H, J=8.3 Hz,
H3), 7.24–7.29 (m, 5H, ArH), 7.40–7.45 (m, 3H, ArH),
7.60–7.64 (m, 2H, ArH). 13C NMR (CDCl3) l 24.8,
25.6, 28.6, 34.0, 46.3, 53.6, 54.9, 55.5, 72.1, 80.2, 83.1,
84.2, 107.7, 113.0, 121.8, 127.6, 127.8, 128.5, 128.6,
128.7, 129.8, 131.6, 136.1, 166.0, 169.2. Anal. calcd for
C29H32F3NO8: C, 60.10; H, 5.57; N, 2.42. Found: C,
60.33; H, 5.42; N, 2.53.

3742
P. Merino et al. / Tetrahedron: Asymmetry 14 (2003) 3731–3743
4.7.8. 4-[(3R,5R)-1-Benzyl-3-[(1S)-1-methoxy-1-phenyl-
1-(trifluoromethyl)acetoxy]-2-oxo-5-pyrrolidinyl]-3-O-
Acknowledgements
benzyl-1,2-O-isopropyliden-a- -xylo-tetrofuranose 17c.
D
(Hexane/Et2O, 60:40; Rf=0.16); 62 mg (95%); oil;
We thank for their support of our programs: the
Spanish Ministry of Science and Technology (MCYT)
and FEDER Program (Project CASANDRA,
BQU2001-2428) and the Government of Aragon (Pro-
ject P116-2001).
1
[h]2D5=−35 (c 0.70, CHCl3); H NMR (CDCl3, 55°C) l
1.27 (s, 3H, CH3), 1.34 (s, 3H, CH3), 2.40 (td, 1H,
J=6.5, 14.2 Hz, H4b), 2.60 (ddd, 1H, J=7.4, 8.8, 14.2
Hz, H4a), 3.56 (s, 3H, OCH3), 3.73 (d, 1H, J=3.3 Hz,
H3%), 3.86 (ddd, 1H, J=4.5, 6.5, 7.4 Hz, H5), 4.19 (d, 1H,
J=15.6 Hz, NCH2Ph), 4.26 (t, 1H, J=3.9 Hz, H4%), 4.31
(d, 1H, J=11.8 Hz, OCH2Ph%), 4.55 (d, 1H, J=3.8 Hz,
H2%), 4.58 (d, 1H, J=11.8 Hz, OCH2Ph%), 4.77 (d, 1H,
J=15.6 Hz, NCH2Ph), 5.63 (dd, 1H, J=6.9, 8.8 Hz,
H3), 5.85 (d, 1H, J=3.8 Hz, H1%), 7.06–7.09 (m, 2H,
ArH), 7.15–7.33 (m, 8H, ArH), 7.36–7.42 (m, 3H,
ArH), 7.57–7.62 (m, 2H, ArH). 13C NMR (CDCl3) l
26.2, 26.7, 27.9, 29.7, 45.2, 53.8, 55.6, 71.4, 71.8, 78.0,
81.7, 82.2, 85.0, 104.4, 111.8, 127.3, 127.6, 127.6, 127.8,
128.2, 128.4, 128.6, 128.8, 129.6, 131.6. 135.8, 136.8,
166.0, 169.6. Anal. calcd for C35H36F3NO8: C, 64.11; H,
5.53; N, 2.14. Found: C, 64.42; H, 5.42; N, 2.21.
References
1. According to the IUPAC recommendations (IUPAC/
IUBMP Pure Appl. Chem. 1996, 68, 1919) ‘cyclic sugar
derivatives in which the ring O-atom has been replaced
by NH have the clase name imino sugar (not aza sugar)’.
In consequence Vogel et al. pointed out that the corre-
sponding disaccharides should be called imino disaccha-
rides and not aza disaccharides. See: Kraehenbuehl, K.;
Picasso, S.; Vogel, P. Helv. Chim. Acta 1998, 81, 1439.
2. (a) Liu, P. S. J. Org. Chem. 1987, 52, 4717; (b) Anzeveno,
P. B.; Creemer, L. J.; Daniel, J. K.; King, C.-H. R.; Liu,
P. S. J. Org. Chem. 1989, 54, 2539.
4.7.9. 5-[(3R,5R)-1-Benzyl-3-[(1S)-1-methoxy-1-phenyl-
1-(trifluoromethyl)acetoxy]-2-oxo-5-pyrrolidinyl]-1,2:3,4-
3. Wong, C.-H.; Krach, T.; Narvor, C. G.-L.; Ichikawa, Y.;
Look, G. C.; Gaeta, F.; Thompson, D.; Nicolau, K. C.
Tetrahedron Lett. 1991, 32, 4867.
di-O-isopropyliden-a-
D
-galacto-pentopyranose
17d.
(Hexane/Et2O, 60:40; Rf=0.22); 60 mg (95%); oil;
1
[h]2D5=+9 (c 0.65, CHCl3); H NMR (CDCl3, 55°C) l
4. Mikkelsen, G.; Christensen, T. V.; Bols, M.; Lundt, I.;
1.25 (s, 3H, CH3), 1.32 (s, 3H, CH3), 1.37 (s, 3H, CH3),
1.57 (s, 3H, CH3), 2.41 (td, 1H, J=7.1, 14.3, H4b), 2.63
(ddd, 1H, J=7.8, 9.1, 14.3 Hz, H4a), 3.55 (s, 3H, OCH3),
3.69 (dt, 1H, J=2.3, 7.3 Hz, H5), 3.99 (dd, 1H, J=7.9,
9.7 Hz, H4%), 3.99 (d, 1H, J=15.5 Hz, NCH2Ph), 4.03
(dd, 1H, J=2.3, 9.7 Hz, H5%), 4.30 (dd, 1H, J=2.0, 5.0
Hz, H2%), 4.55 (dd, 1H, J=2.0, 7.9 Hz, H3%), 5.22 (d, 1H,
J=15.5 Hz, NCH2Ph), 5.54 (d, 1H, J=5.0 Hz, H1%),
5.58 (dd, 1H, J=7.1, 9.1 Hz, H3), 7.10–7.70 (m, 10H,
ArH). 13C NMR (CDCl3) l 24.0, 24.5, 25.6, 26.2, 26.8,
43.9, 54.9, 55.5, 63.6, 70.1, 71.2, 71.5, 71.9, 85.0, 96.5,
108.2, 109.4, 123.2, 127.7, 127.8, 128.4, 128.9 (2C),
129.6, 131.6, 135.6, 166.2, 169.6. Anal. calcd for
C32H36F3NO9: C, 60.47; H, 5.71; N, 2.20. Found: C,
60.35; H, 5.82; N, 2.28.
Sierks, M. R. Tetrahedron Lett. 1995, 36, 6541.
5. (a) Vonhoff, S.; Heightman, T. D.; Vasella, A. Helv.
Chim. Acta 1998, 81, 1710; (b) McCort, I.; Dureault, A.;
Depezay, J.-C. Tetrahedron Lett. 1998, 39, 4463; (c) Ble-
riot, Y.; Dintinger, T.; Guillo, N.; Tellier, C. Tetrahedron
Lett. 1995, 36, 5175.
6. (a) Suzuki, K.; Hashimoto, H. Tetrahedron Lett. 1994,
35, 4119; (b) Campanini, L.; Dureault, A.; Depezay, J.-C.
Tetrahedron Lett. 1996, 37, 5095.
7. These compounds can also be called C-linked imino
disaccharides, but not aza-C-disaccharides. See Ref. 1.
8. Duff, F. J.; Vivien, V.; Wightman, R. H. Chem. Commun.
2000, 2127.
9. (a) Jonhson, C. R.; Miller, M. W.; Golebiowski, A.;
Sundram, H.; Ksebati, M. B. Tetrahedron Lett. 1994, 35,
8991; (b) Johns, N. A.; Pan, Y. T.; Elbein, A. D.;
Johnson, C. R. J. Am. Chem. Soc. 1997, 119, 4856; (c)
Johns, B. A.; Johnson, C. R. Tetrahedron Lett. 1998, 39,
749.
10. See inter alia: (a) Zhu, Y.-H.; Vogel, P. Chem. Commun.
1999, 1873; (b) Zhu, Y.-H.; Vogel, P. J. Org. Chem. 1999,
64, 666; (c) Frerot, E.; Marquis, C.; Vogel, P. Tetra-
hedron Lett. 1996, 37, 2023; (d) Baudat, A.; Vogel, P. J.
Org. Chem. 1997, 62, 6252; (e) Baudat, A.; Vogel, P.
Tetrahedron Lett. 1996, 37, 483.
11. (a) Martin, O. R.; Liu, L.; Yang, F. Tetrahedron Lett.
1996, 37, 1991; (b) Dondoni, A.; Giovanninin, P. P.;
Perrone, D. J. Org. Chem. 2002, 67, 7203; (c) Andreassen,
V.; Svensson, B.; Bols, M. Synthesis 2001, 339.
12. (a) Cardona, F.; Salanski, P.; Chmielewski, M.; Valenza,
S.; Goti, A.; Brandi, A. Synlett 1998, 1444; (b) Cardona,
F.; Valenza, S.; Goti, A.; Brandi, A. Tetrahedron Lett.
1997, 38, 8097; (c) Cardona, F.; Valenza, S.; Picasso, S.;
Goti, A.; Brandi, A. J. Org. Chem. 1998, 63, 7311.
13. (a) Merino, P.; Anoro, S.; Franco, S.; Merchan, F. L.;
Tejero, T.; Tunon, V. J. Org. Chem. 2000, 65, 1590; (b)
4.7.10. 5-[(3R,5S)-1-Benzyl-3-[(1S)-1-methoxy-1-phenyl-
1-(trifluoromethyl)acetoxy]-2-oxo-5-pyrrolidinyl]-1,2:3,4-
di-O-isopropyliden-a-
D
-galacto-pentopyranose
17e.
(Hexane/Et2O, 60:40; Rf=0.24); 60 mg (95%); oil;
1
[h]2D5=+85 (c 0.25, CHCl3); H NMR (CDCl3, 55°C) l
1.23 (s, 3H, CH3), 1.32 (s, 3H, CH3), 1.34 (s, 3H, CH3),
1.55 (s, 3H, CH3), 2.11 (ddd, 1H, J=4.4, 8.4, 13.6 Hz,
H4b), 2.54 (ddd, 1H, J=1.8, 8.1, 13.6 Hz, H4a), 3.53 (s,
3H, OCH3), 3.78 (dd, 1H, J=1.8, 4.4 Hz, H5), 3.79 (s,
1H, H5%), 4.12 (d, 1H, J=7.9 Hz, H4%), 4.26 (d, 1H,
J=14.5 Hz, NCH2Ph), 4.31 (dd, 1H, J=2.5, 5.0 Hz,
H2%), 4.55 (dd, 1H, J=2.5, 7.9 Hz, H3%), 5.10 (d, 1H,
J=14.5 Hz, NCH2Ph), 5.55 (d, 1H, J=5.0 Hz, H1%),
5.69 (t, 1H, J=8.2 Hz, H3), 7.18–7.29 (m, 5H, ArH),
7.37–7.43 (m, 3H, ArH), 7.57–7.64 (m, 2H, ArH). 13C
NMR (CDCl3) l 24.4, 24.8, 25.8, 26.2, 29.7, 46.3, 54.0,
55.5, 64.6, 69.7, 70.2, 70.8, 72.5, 84.9, 96.3, 109.0, 109.9,
121.3, 127.7, 127.8, 128.5, 128.6, 128.7, 129.8, 131.6,
135.9, 166.2, 169.6. Anal. calcd for C32H36F3NO9: C,
60.47; H, 5.71; N, 2.20. Found: C, 60.35; H, 5.77; N,
2.17.

P. Merino et al. / Tetrahedron: Asymmetry 14 (2003) 3731–3743
3743
Merino, P.; Mates, J. A.; Revuelta, J.; Tejero, T.; Chiac-
chio, U.; Romeo, G.; Iannazzo, D.; Romeo, R. Tetra-
hedron: Asymmetry 2002, 12, 173.
Tejero, T. Synth. Commun. 1994, 22, 2200.
17. (a) Kusumi, T.; Fukushima, T.; Ohtani, I.; Kakisawa, H.
Tetrahedron Lett. 1991, 32, 2939; (b) Sullivan, G. R.;
Dale, J. A.; Mosher, H. S. J. Org. Chem. 1973, 38, 2143;
(c) Dale, J. A.; Mosher, H. S. J. Am. Chem. Soc. 1973,
95, 512; (d) Dale, J. A.; Dull, D. L.; Mosher, H. S. J.
Org. Chem. 1969, 34, 2543; (e) Latypov, Sh. K.; Seco, J.
M.; Quin˜oa, E.; Riguera, R. J. Org. Chem. 1996, 61,
8569.
18. The authors have deposited the atomic coordinates for
this structure with the Cambridge Crystallographic Data
Centre. The coordinates can be obtained on request from
the Director, Cambridge Crystallographic Data Centre,
12 Union Road, Cambridge CB2 1EZ, UK. The deposi-
tion number is CCDC 218370. The graphic view showed
in Figure 2 was made with ORTEP3 software. Copyright
by Farrugia, L. J., University of Glasgow, 1997–2000.
14. The N and C symbols included into the general name
‘N-benzyl-C-glycosyl nitrones’ refer to the groups linked
to the nitrogen and carbon atoms, respectively, of the
nitrone functionality (R1CHꢀN+(O−)R2, where R1=ben-
zyl and R2=glycosyl).
15. (a) Kusumi, T.; Fukushima, T.; Ohtani, I.; Kakisawa, H.
Tetrahedron Lett. 1991, 32, 2939; (b) Sullivan, G. R.;
Dale, J. A.; Mosher, H. S. J. Org. Chem. 1973, 38, 2143;
(c) Dale, J. A.; Mosher, H. S. J. Am. Chem. Soc. 1973,
95, 512; (d) Dale, J. A.; Dull, D. L.; Mosher, H. S. J.
Org. Chem. 1969, 34, 2543; (e) Latypov, Sh. K.; Seco, J.
M.; Quin
8569.
16. Dondoni, A.; Franco, S.; Merchan, F. L.; Merino, P.;
1 oa, E.; Riguera, R. J. Org. Chem. 1996, 61,