The use of anhydroiminocyclitols as glycosyl donors in glycosidation reactions

Article abstract of DOI:10.1016/j.tet.2010.09.065

High yielding synthesis of six- and five-membered N-substituted iminosugar glycosides and of five-membered iminosugar thioglycosides by nucleophilic opening of both new and previously described N-diethoxycarbonylvinyl anhydroiminosugar derivatives (glycos

Full text of DOI:10.1016/j.tet.2010.09.065

Tetrahedron 66 (2010) 9214e9222
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
The use of anhydroiminocyclitols as glycosyl donors in glycosidation reactions
a
,
a
b
a
*
ꢀ
ꢀ
Jose Fuentes , Nader R. Al Bujuq , Manuel Angulo , Consolacion Gasch
a
ꢀ
ꢀ
Departamento de Quõmica Organica, Universidad de Sevilla, Apartado 1203, E-41071 Sevilla, Spain
b Servicio de RMN, Universidad de Sevilla, Apartado 1152, E-41071 Sevilla, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 12 May 2010
Received in revised form 7 September 2010
Accepted 17 September 2010
Available online 24 September 2010
High yielding synthesis of six- and five-membered N-substituted iminosugar glycosides and of five-
membered iminosugar thioglycosides by nucleophilic opening of both new and previously described N-
diethoxycarbonylvinyl anhydroiminosugar derivatives (glycosyl donors) with primary alcohols, primary
thiols, and thiophenol (glycosyl acceptors) is reported. The reactions are highly stereoselective, with
anomeric ratios better than 4:1.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Iminosugar
Iminocyclitol
Azasugar
Glycosyl donor
Glycosidation reaction
Thioglycoside
Glycoside
1. Introduction
and thioglycosides starting from 1,2-O-isopropylidene furanosyl
derivatives has been reported by Schmidt.15 The author has used
In the past decade the stereoselective syntheses of highly
functionalized molecules, such as natural and pharmaceutically
important compounds, have been a challenge in organic chemis-
try.1 Carbohydrate derivatives, due to their numerous stereogenic
centers, anomeric reactivity, and conformational properties, play an
important role in these syntheses, where can be considered as
targets or as key chiral intermediates.2 Particularly, iminocyclitols,
also known as iminosugars, are glycosidase and glycosyltransferase
inhibitors and consequently they can be useful in the treatment of
metabolic disorders and inflammatory processes.3,4 It is not sur-
prising that this therapeutical potential has generated a huge in-
terest in the syntheses and structural modifications of iminosugars,
and many short and stereoselective routes have been reported.5 We
have described a versatile procedure to prepare five6-, six7-, and
seven8-membered iminosugars, starting from glycosylenamines
and being the key chiral intermediate an anhydroiminosugar.
The data on the preparation of iminosugar glycosides (1) and
iminosugar thioglycosides (2) are limited. Multistep, low-yielding
syntheses of 2-alkoxy polyhydroxypiperidines have been repor-
ted.9,10 Six-membered iminosugar glycosides have been used as
intermediates to prepare monocyclic11e13 and bicyclic azasugars.14
A method for the synthesis of six-membered azasugar glycosides
the glycosidation reaction, with trichloroacetimidates as glycosyl
donors, to prepare nojirimycin thioglycosides.16 Hashimoto17 has
reported the first synthesis of an ethyl thioglycoside of a thio-
disaccharide having one iminosugar moiety. Later, we have de-
scribed18 the synthesis of six-membered iminosugar thioglycosides
starting from an anhydroiminosugar with D-ribo configuration.
Regarding the preparation of five-membered iminosugar gly-
cosides, Schmidt19 has described a multistep synthesis of a methyl
iminoriboside, and we have reported20 the preliminary data on the
use of an anhydroiminocyclitol, particularly with D-galacto config-
uration, as glycosyl donor in glycosidation reactions, but only
methanol was used as glycosyl acceptor. The bibliographic data on
five-membered iminocyclitol derivatives having a thioalkoxy group
on the pseudoanomeric carbon atom are very scarce, and limited to
thioanalogues of the indolizidine alkaloid castanospermine having
the sulfur atom taking part in the five-membered ring.21
* Corresponding author. Tel.: þ34 954551518; fax: þ34 954624960; e-mail
address: jfuentes@us.es (J. Fuentes).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.09.065

J. Fuentes et al. / Tetrahedron 66 (2010) 9214e9222
9215
In a recent letter22 we have communicated our preliminary re-
sults on the use of iminosugar thioglycosides as glycosyl donors in
glycosidation reactions. Continuing our work on the chemistry of
iminosugars,18,23 herein we present the preparation of a new
anhydroiminosugar (13) and the use of this type of compounds to
prepare six-(5e7) and five-(14e19)-membered iminosugar glyco-
sides, and five-membered (21e27) iminosugar thioglycosides.24
Fig. 1. Intermediate cation in the formation of 5e7.
2. Results and discussion
The chemical shift (see Experimental) for the resonances of H-2
and C-2 (pseudoanomeric position) in 5e7 and the appearance of
a doublet at 2.07e2.15 ppm for the OH group support the ring
opening and the formation of a new glycosidic bond. A double
pulsed field gradient spin echo (DPFGSE-NOE) experiment,25 per-
formed on H-5, was used to assess the configuration of C-2. NOE
spectra data (Fig. 2) revealed important correlations between the
endo-methyl protons of the isopropylidene group an H-6b, and
between the methyl group of the aglycone and H-6a. All data were
in agreement with S-configuration for C-2.
2.1. Synthesis of six- and five-membered iminosugar
glycosides
The starting material to prepare the six-membered iminosugar
glycosides 5e7 (pyranoside analogues) is the anhydroiminosugar
418 (Scheme 1), which was easily prepared from the furanosylen-
amine 3, using the capability of the alkoxycarbonylvinyl group to
stabilize a negative charge on the nitrogen atom, and to produce an
internal substitution8 (see Fig. 3). Reaction of the glycosyl donor 4
with methanol, butanol, and allyl alcohol as glycosyl acceptors, in
the presence of BF3$OEt2 produced the corresponding iminosugar
glycoside (5e7) in almost quantitative yield and only as b-anomer.
Probably, the coordination of 4 with BF3 produce an oxocation
(Fig. 1) facilitating the attack of the alcohol. The stereoselectivity for
the formation of the
b-anomer, is due to the steric hindrance of the
a
-attack caused by the isopropylidene group.
Fig. 2. Diagnostic NOE observation for compounds 5 and 20.
Fig. 3. Intermediate amide ion for the formation of 13.
We have carried out several attempts of glycosidation of cyclo-
hexanol, a secondary alcohol, with 4 but the reaction was un-
successful, probably due to the steric hindrance. The corresponding
cyclohexyl iminosugar glycoside could be obtained using a thio-
glycoside as glycosyl donor, as we have reported in a previous
communication.22
The key chiral intermediate to prepare the five-membered imi-
nosugar glycosides 14e19 (furanoside analogues) was the anhy-
droiminocyclitol 13 (Scheme 1), which was prepared from the
D
-xylopyranosylenamine 8,26 following a modification of the
reported method for the synthesis of other anhydroiminocyclitols.6
Dibutyltin oxide derivatives have been extensively employed as in-
termediates in the regioselective derivatization of carbohydrates.27
At the same time, the tosyl group is useful in the field of carbohy-
drate chemistry as activating group28 for substitution reactions.
However, the preparation of a particular mono-O-tosyl derivative
often requires multistep and low-yielding syntheses. The regiose-
lective benzoylation29 and tosylation30 of various non-protected
monosaccharide derivatives after activation of a hydroxyl group
with dibutyltin oxide have been reported.31
The treatment of 8 with dibutyltin oxide in the presence of
dimethylaminopyridine (DMAP), followed by the addition of tosyl
Scheme 1. Synthesis of glycosides.

9216
J. Fuentes et al. / Tetrahedron 66 (2010) 9214e9222
chloride selectively produced the 4-O-tosyl derivative 9. When the
same reaction was performed using mesyl chloride instead of tosyl
chloride, compound 10 was the major product but the yield was
low and other regioisomers were detected. The presence of the 4-
O-sulfonyloxy group in 9 and 10 was confirmed by NMR spectra
(see Experimental), which showed the described32 downfield shifts
for the resonances of H-4 (Dd, 0.80e0.94 ppm) and C-4 (Dd, 7.6),
and the upfield shifts for the resonances of C-3 (Dd, ꢀ2.1 ppm) and
C-5 (Dd, ꢀ2.4 to ꢀ1.8 ppm) with respect to the same signals for 8.
Conventional acetylation23 of 9 and 10 yielded, respectively, 11
and 12 whose spectroscopic data also confirmed the structures of 9
and 10.
Scheme 2. Formation of compound 20.
Treatment of 11 with 1 equiv of sodium methoxide in hexam-
2.2. Synthesis of five-membered iminosugar thioglycosides
ethyl phosphoramide (HMPA) afforded the 1,4-anhydro-a-L-arabi-
nopyranosylamine 13, whose formation could be explained
through the formation of a stabilized amide ion (Fig. 3).
When the 1H NMR spectrum of 13 is compared with that for 11,
the disappearance of the NH signal, and the resonance for the HC],
of the enamino moiety, as a singlet was observed. Additionally, the
signal for H-1 was downfield shifted, whereas the resonance for H-
4 was upfield shifted, which is in agreement with the substitution
of the C-tosyloxy group by the enamino group. Also important
changes in the coupling constant values for the sugar ring were
observed.
The starting material to prepare the five-membered iminosugar
thioglycosides 21e27 was the 1,4-anhydro-L-arabinopyranosyl-
amine 13 (Scheme 3). Thus, reaction of 13, as glycosyl donor, and
thiols (ethanethiol, butanethiol, p-tolylphenol, and 1,4-butanedi-
thiol) as glycosyl acceptors, in the presence of BF3$OEt2, produced
21e27 as resoluble pairs of anomers, except in the case of the
butanedithiol where only the
a anomer 24 was isolated.
Reaction of 1,4-anhydroiminosugar 13 with methanol, butyl
alcohol, and benzyl alcohol in the presence of boron trifluoride
diethyl etherate afforded (Scheme 1) the five-membered imino-
sugar glycosides (furanoside analogues) 14e19 as resoluble pairs of
anomers (14, 17; 15, 18; and 16, 19, respectively). The alcohols were
used as reagents and solvents, except in the case of 16 and 19 where
ether was used as solvent. The substitution reaction occurred rap-
idly and the products were formed within 30 min at rt. When the
reaction mixtures of butanol and benzyl alcohol were left for longer
times, some transacetylations (from C-4 to C-6) were observed and
confirmed by NMR spectroscopy. Table 1 shows the reaction con-
ditions, yields, and anomeric ratios, which were determined by 1H
NMR spectroscopy. The mixtures of anomers were chromato-
graphically resolved.
Table 1
Reaction conditions for compounds 14e19
Nucleophile
Solvent
Temperature
Products
a
:b
ratio
Yield (%)
MeOH
BuOH
BnOH
Methanol
Butanol
Ether
rt
rt
rt
14 and 17
15 and 18
16 and 19
3:2
3:2
3:1
86
84
82
The NMR data (see Experimental) for the sugar ring nuclei of
compounds 14e19 were similar to those for the corresponding
anomers of methyl a- and b-L
-furanosides.33,34 The NMR spectra of
compounds 14e16 were very similar; in the three cases the signal
for H-2 was a broad singlet (J2,3<0.5 Hz) in accord with the data of
a-L-furanosides. However, the same proton for compounds 17e19
resonated as a doublet (J2,3¼4.8e5.0 Hz) as is reported for
b-L-
furanosides.
When the reaction of 13 was attempted with a secondary al-
cohol, such as cyclohexanol, as glycosyl donor a mixture of com-
pounds was obtained, from which only the 5-aminoglycoside 20
was isolated in medium yield (Scheme 2). The formation of 20 in-
volves a rearrangement of the enamino moiety from the position 2
to the position 5. A similar reaction has been reported for related
compounds.20 The resonances for the NH of 20 was a double
doublet and the proton ]CH resonated as a doublet. NOE experi-
ments (Fig. 2) revealed correlations in the space between protons
NH and H-3, and also between NH and H-2, supporting the
Scheme 3. Synthesis of thioglycosides.
Different experiments, performed on the synthesis of ethyl (21,
25) and butyl (22, 26) derivatives, were carried out to establish the
optimal reaction conditions (see Table 2). The best results (high
yields without side products, and high anomeric selectivities) were
obtained under the conditions of entries 2 and 9, that is, using ether
as solvent and rt.
The 1H NMR spectra (see Experimental) of 21e27 showed a sin-
glet at z7.50 ppm, which corresponds to the HC]group of the
enamino moiety, and a broad signal in the range 2.4e2.3 ppm
b-L-anomeric configuration.

J. Fuentes et al. / Tetrahedron 66 (2010) 9214e9222
9217
Table 2
4. Experimental
Optimization conditions for the reactions of 13 with thiols
4.1. General methods
Entry Nucleophile Solvent Temperature Products
a:b ratio
1
2
3
4
5
6
7
8
9
10
EtSH
EtSH
EtSH
EtSH
EtSH
EtSH
BuSH
BuSH
BuSH
BuSH
DMFa
Ether
Ether
Ether
Ether
Ether
0
rt
0
ꢂC
25 and side products
21, 25
21, 25
21, 25
21, 25
1:0
5:1
4:1
5:3
5:3
4:3
Unless otherwise noted, starting materials were obtained for
commercial suppliers and used without purification. All manipula-
tions of air-sensitive compounds were carried out in an inert atmo-
sphere under recirculation of nitrogen or argon. The following
reaction solvents were distilled under nitrogen immediately before
use: THF and Et2O from Na/benzophenone; CH2Cl2 from CaH2; tol-
uene from Na; and MeOH from Mg. Et2O and petroleum ether for
column chromatography were also distilled under nitrogen from Na/
ꢂC
ꢀ5 ꢂC
ꢀ35 ꢂC
ꢀ75 ꢂC
21, 25
Toluenea rt
22, 26, and side products 4:1
22, 26, and side products 4:1
22, 26
CH3CNa rt
Ether
rt
4:1
Toluenea 45 ꢂC
22, 26, and side products 4:1
a
The total yield was low or very low due, in part, to the formation of side-
benzophenone before use. TLC were performed on silica gel HF254
,
products.
with visualization by UV light or charring with 10% H2SO4 (EtOH) or
1% Ce(SO4)2$4H2O-5% ammonium molybdate-6% H2SO4. Silica gel 60
(Merck, 70e230 or 230e400 mesh) was used for preparative chro-
matography. A PerkineElmer model 141 MC polarimeter, tubes of
1 cm, and solutions in CH2Cl2, unless other stated, at 589 nm, were
usedformeasurementsofspecificrotations. IRspectrawererecorded
for KBr discs or films on a Bomen Michelson MB 120 FTIR spectro-
photometer. Mass spectra (EI, CI, and FAB) were recorded with
a Kratos MS-80RFA or a Micromass AutoSpecQ instrument with
a resolution of 1000 or 60,000 (10% valley resolution). For the FAB
spectra; ions were produced by a beam of xenon atoms (6e7 KeV),
using3-nitrobenzylalcoholorthioglycerolasmatrixandNaIassalt.A
corresponding to the OH group; both signals are indicative of ring
opening by cleavage of the CeO bond. In the 13C NMR spectra the
signals for C-2 appeared upfield shifted with respect to the same
resonances for the glycosides 14e19, as corresponds to the sub-
stitution of an oxygen atom bya sulfur atom.35 The
b configuration of
compound 27 was deduced from the J2,3 value (5.8 Hz), similar to
that for 17e19. However, for compounds 21e26, resonances of the
protons H-2 and H-3 appeared very close, and NOE experiments
were necessary to confirm the anomeric configurations. In every
case appeared correlations confirming the configurations indicated
in Scheme 3. As examples, Fig. 4 shows the NOE contacts in ethyl
Waters 2690 instrument, with a PDA 996 detector, and a mBondpack
thioglycosides 21 and 25. The
correlations between H-5 and SeCH2, between H-2 and H-4, and
between H-2 and H-6. The configuration of 25 is in agreement with
a configuration of 21 is supported by
C18 column (7.8ꢁ300 mm) was used for HPLC. NMR experiments
were recorded on a Bruker AMX 500 (500.13 MHz for 1H and
125.75 MHz for 13C) or on a Bruker AMX300 (300.5 MHz for 1H and
75.50 MHz for 13C). Sample concentrations were typically in the
range 10e15 mg per 0.5 mL of solvent. Chemical shifts are given in
parts per million, and tetramethylsilane was the internal standard.
2D COSY, HMQC, TOCSY, HMBC, and 1D NOESY experiments were
carried out to assist in NMR signal assignments.
b
NOE contacts between H-2 and H-5 and between H-4 and SeCH2.
Compounds 3,35 4,18 and 826 were prepared according to the
described literature procedures.
4.2. General procedure for the synthesis of glycosides 5e7
To a stirred solution of compound 4 (x mg) in the corresponding
dry alcohol (methanol for 5, butanol for 6, and allyl alcohol for 7)
Fig. 4. Diagnostic NOE observations for compounds 21 and 25.
ꢂ
ꢁ
(y mL), over 4 A molecular sieves, at 0 C, boron trifluoride diethyl
etherate (z l) was added. The reaction mixture was stirred for
Treatment of compounds 23 and 27 with resin Amberlite IRA-
400 (OH) for 12 h produced de-O-acetylation with formation of 28
and 29, respectively, in high yield (Scheme 3). Longer reaction time
(tested on 28) produced transesterification and the bicyclic de-
rivative 30 was isolated. No N-deprotection36 was observed. Several
attempts of N-deprotection using other described procedures26 for
N-dialcoxycarbonyl-2-aminosugars, only gave irresolvable mix-
tures of decompositions products.
m
45 min, then neutralized with saturated aqueous NaHCO3 and
extracted with CH2Cl2. The organic layer was washed with water,
dried over MgSO4, and concentrated to dryness. The residue was
purified by column chromatography (ether/hexane 1:2).
4.2.1. (2S,3R,4R,5R)-N-(2,2-Diethoxycarbonylvinyl)-3,4,5-trihydroxy-
3,4-O-isopropylidene-2-methoxypiperidine (5). x¼150 mg (0.44 mmol);
y¼10 mL; z¼250
m
l. Solid (133 mg; 81%). [
a
]
22 ꢀ32 (c 1.0, CH2Cl2); IR:
D
3. Conclusions
nmax 3447, 2884, 2935, 1692, 1598, 1383, 1268, 1171, 1091, 905 cmꢀ1; 1H
NMR: (300 MHz, CDCl3)
d
7.44 (s, 1H, HC]), 4.48 (dd, J2,3¼2.4, J3,4¼7.8,
Six- and five-membered N-diethoxycarbonylvinyl iminosugar
glycosides, and five-membered N-diethoxycarbonylvinyl iminosu-
gar thioglycosides are obtained in good yields through glyco-
sidation reactions using anhydro-iminosugars as glycosyl donors
and primary alcohols or thiols (p-tolylthiophenol) as glycosyl ac-
ceptors. The glycosidations were completely stereoselective in the
pseudoanomeric position for piperidine derivatives (pyranoid an-
alogues), whereas in the case of pyrrolidine derivatives (furanoid
analogues) resoluble mixtures of anomers were obtained. When
the glycosidation reaction was tried using cyclohexanol (a sec-
ondary alcohol) as an acceptor a rearrangement of the enamino
1H, H-3), 4.39 (d, 1H, H-4), 4.37 (m, 2H, H-2, H-5), 4.26, 4.16 (each q,
each 2H, JH,H¼7.0, 2COOCH2CH3), 3.37 (dd, 1H, J5,6a¼6.0, J6a,6b¼11.4, H-
6a), 3.30 (s, 3H, OCH3), 3.11 (t, 1H, J5,6b¼11.4, H-6b), 2.07 (d, 1H,
J5,OH¼10.4, OH-5), 1.43, 1.33 [each s, each 3H, (CH3)2C], 1.32, 1.24 (each
t, each 3H, 2COOCH2CH3); 13C NMR: (125.7 MHz, CDCl3)
d 167.6, 167.0
(2C]O),149.5 (HC]), 110.8 (C(CH3), 96.7 (]C), 93.4 (C-2), 74.7 (C-4),
73.4 (C-3), 63.5 (C-5), 61.2, 60.4 (2COOCH2CH3), 55.6 (OCH3), 45.3 (C-
6), 26.2, 24.6 [2 (CH3)2C)], 14.7, 14.3 (2COOCH2CH3). Anal. Calcd for
C17H27NO8: C, 54.68; H, 7.29; N, 3.75. Found: C, 54.88; H, 7.17; N, 3.74.
4.2.2. (2S,3R,4R,5R)-2-Butoxy-N-(2,2-diethoxycarbonylvinyl)-3,4,5-
moiety took place and a 4-amino-4-deoxy-
was obtained.
L-arabinoside derivative
trihydroxy-3,4-O-isopropylidenepiperidine (6). x¼77 mg (0.41 mmol);
y¼8 mL; z¼250
m
l. Syrup (136 mg; 80%). [
a
]
22 ꢀ11 (c 1.0, CH2Cl2); IR:
D

9218
J. Fuentes et al. / Tetrahedron 66 (2010) 9214e9222
nmax 3447, 2929, 1682, 1593, 1376, 1276, 1206, 1164, 1082, 946,
899 cmꢀ1; 1H NMR: (300 MHz, CDCl3)
7.44 (s, 1H, HC]), 4.54 (dd,
Anal. Calcd for C20H27NO10S: C, 50.73; H, 5.75; N, 2.96; S, 6.77.
Found: C, 50.32; H, 5.78; N, 2.99; S, 6.20%.
d
J5,6¼7.8, J4,5¼2.8,1H, H-5), 4.41 (d,1H, J2,3¼1.5, H-2), 4.41 (br s,1H, H-
3), 4.39 (d, 1H, J3,4¼1.5 Hz, H-4) 4.29, 4.19 (each q, each 2H, JH,H¼7.0,
2COOCH2CH3), 3.58 (dd, 1H, J5,6a¼6.5, J6a,6b¼12.0, H-6a), 3.36 [m, 2H,
OCH2(CH2)2CH3], 3.12 (t, 1H, J5,6b¼10.8, H-6b), 2.14 (d, 1H, J5,OH¼10.5,
OH-5), 1.53 (m, 2H, OCH2CH2CH2CH3), 1.45, 1.36 [each s, each 3H,
(CH3)2C], 1.31, 1.26 (each t, each 3H, 2COOCH2CH3), 0.934 (m, 5H,
4.3.2. N-(2,2-Diethoxycarbonylvinyl)-4-O-mesyl-
amine (10). x¼5.00 (15.6 mmol); y¼4.70
z¼2,00 mL (17.5 mmol). Syrup (3.92 g; 63%). [
CH2Cl2); IR: nmax 3901, 3837, 3750, 3674, 3648, 3566, 3617, 1942,
1918, 1733, 1670, 1575, 1361, 1071, 961, 669 cmꢀ1 1H NMR:
(500 MHz, CDCl3)
b
-
g
]
D
-xylopyranosyl-
(18.7 mmol);
þ40.2 (c 1.0,
g
22
a
D
;
OCH2CH2CH2CH3); 13C NMR: (125.7 MHz, CDCl3):
d
167.5,166.9 (2C]
d
9.26 (dd, JNH,]CH¼13.6, JNH,1¼8.3, 1H, NeH),
O), 149.4 (HC]), 110.7 [C(CH3)2], 96.1 (]C), 92.0 (C-2), 74.7 (C-4),
73.2 (C-3), 67.9 [OCH2(CH2)2CH3], 63.5 (C-5), 61.1, 60.3
(2COOCH2CH3), 45.28 (C-6), 31.27 (OCH2CH2CH2CH3), 26.0, 24.4 [2
(CH3)2C], 19.32 (OCH2CH2CH2CH3), 14.3, 14.1 (2COOCH2CH3), 13.7
(OCH2CH2CH2CH3); HRFABMS: calcd for C13H25N2O5Na: 311.1583.
Found: 311.1589.
8.02 (d, 1H, HC]), 4.54 (m, 1H, H-4), 4.34 (t, J1,2¼8.3 Hz, 1H, H-1),
4.24e4.08 (m, 3H, 2COOCH2CH3, H-5b), 3.74 (t, J2,3¼8.9, H-3),
3.55e3.47 (m, 2H, H-2, H-5b), 3.15(s, 3H, OSO2CH3), 1.30, 1.27 (each
t, each 3H, 2COOCH2CH3); 13C NMR: (125.7 MHz, CDCl3)
d 168.7,
166.2 (2C]O), 158.3 (HC]), 93.5 (]C), 88.7 (C-1), 77.0 (C-4), 74.4
(C-3), 73.5 (C-2), 65.4 (C-5), 60.6, 60.4 (2COOCH2CH3), 38.4
(OSO2CH3) 14.4, 14.3 (2COOCH2CH3); HRFABMS: calcd for
C14H24NO10S: 398.1094. Found: 398.1121.
4.2.3. (2S,3R,4R,5R)-2-Allyloxy-N-(2,2-diethoxycarbonylvinyl)-3,4,5-
trihydroxy-3,4-O-isopropylidenepiperidine (7). x¼110 mg (0.32 mmol);
y¼8 mL; z¼100
m
l. Syrup (110 mg; 85%). [
a
]
22 ꢀ33.0 (c 1.0, CH2Cl2); IR:
4.4. General procedure for the synthesis of compounds
11 and 12
D
nmax IR: 3433, 2917, 1623, 1376, 1206, 1164, 1088, 864 cmꢀ1; 1H NMR:
(300 MHz, CDCl3): d 7.43 (s, 1H, NCH]), 5.82 (m, 1H, OCH2CH]CH2),
5.29 (t, 2H, J]CH,]CH2¼14.7, OCH2CH]CH2), 4.57 (dd, J5,4¼2.7, J5,6¼9.4
1H, H-5), 4.47 (d, 1H, J2,3¼1.5, H-2), 4.44 (br s, 1H, H-4), 4.40 (d, 1H, H-
3), 4.29, 4.19 (each q, each 2H, JH,H¼7.2, 2COOCH2CH3), 4.09 (d, 1H,
To a stirred solution of 8 or 9 (x g) in pyridine (50 mL) at rt, acetic
anhydride (10 mL) was added. The reaction mixture was stirred at
rt for 4.0 h and then was added over ice-water (200 mg) and
extracted with CH2Cl2 (2ꢁ100 mL). The organic layer was washed
successively with H2SO4 (20 mL, 1 M), saturated aqueous NaHCO3
(20 mL) and H2O (20 mL), dried over MgSO4, and evaporated to
dryness. The dark residue obtained was purified by column chro-
matography (ethyl acetate/hexane 1:2).
JOCHa ]CH
,
¼4.8, OCHaHb), 3.94 (dd, 1H, JOCHb ]CH¼6.6, JHa,Hb¼14.8,
,
OCHaHb), 3.40 (dd, 1H, J5,6a¼6.0, J6a,6b¼11.4, H-6a), 3.17 (t, 1H,
J5,6b¼11.1, H-6b), 2.15 (d, 1H, J5,OH¼10.2, OH-5), 1.44, 1.32 (each s, each
3H, [(CH3)2C]), 1.31, 1.26 (each t, each 3H, 2COOCH2CH3); 13C NMR:
(125.7 MHz, CDCl3)
d 167.5, 166.8 (2C]O), 149.3 (HC]), 132.7
(CH2CH]CH2), 119.0 (OCH2CH]CH2) 110.7 [C(CH3)2], 96.5 (]C), 90.4
(C-2), 74.7 (C-4), 73.2 (C-3), 68.3 (OCH2CH]CH2), 63.4 (C-5), 61.1, 60.2
(2COOCH2CH3), 45.28 (C-6), 26.0, 24.4 (2 [(CH3)2C)], 14.3, 14.1
(2COOCH2CH3); HRFABMS: calcd for C19H29NO8Na: 422.1791. Found:
422.1783.
4.4.1. 2,3-Di-O-acetyl-N-(2,2-diethoxycarbonylvinyl)-4-O-tosyl-b-D-
xylopyranosylamine (11). From 8; x¼3.60 g (7.6 mmol). Syrup
(3.50 g; 82%). [
a
]
22 ꢀ56.5 (c 1.0, CH2Cl2); IR: nmax 3848, 3737, 3649,
D
3557, 2985, 2367, 2332, 1749, 1707, 1649, 1370, 1212, 1060 cmꢀ1; 1H
NMR: (500 MHz, CDCl3)
d
9.25 (dd, JNH,]CH¼13.1, JNH,1¼8.8, 1H, NH),
7.90 (d, 1H, HC]), 7.78, 7.76, 7.37, 7.35 (4H, Ph), 5.21 (t, J2,3¼J3,4¼8.5,
1H, H-3), 4.90 (t, J1,2¼8.5, 1H, H-2), 4.52 (m, 1H, H-4), 4.48 (t, 1H, H-
1), 4.26e4.10 (m, 3H, 2COOCH2CH3, H-5a), 3.52 (dd, J5a,5b¼12.0,
J4,5b¼9.7, 1H, H-5b), 2.45 (s, 3H, PheCH3), 1.99,1.84 (each s, each 3H,
2COCH3), 1.30, 1.27 (each t, each 3H, 2COOCH2CH3); 13C NMR:
4.3. General procedure for the synthesis of compounds
9 and 10
A mixture of 8 (x g) and dibutyltin oxide (y g) was heated under
reflux in dry toluene (100 mL) for 3 h. The solution was evaporated
to dryness and the dark brown residue obtained was dissolved in
dioxane (50 mL). Then, p-toluenesulfonyl chloride (TsCl) for 9, or
methanesulfonyl chloride (MsCl) for 10 (z g or mL), and DMAP
(catalytic amount) were added. The reaction mixture was stirred at
rt for 4.0 h. Water (10 mL) was added and the mixture was
extracted by CH2Cl2 (2ꢁ50 mL). The organic layer was washed by
saturated aqueous NaHCO3 (30 mL) and water (30 mL), dried over
MgSO4, and evaporated to dryness. The crude product was purified
by column chromatography (ethyl acetate/hexane 2:3).
(125.7 MHz, CDCl3) d 169.6,169.4,167.9,165.4 (4C]O),157.2 (HC]),
145.6, 133.1, 130.2, 128.0 (Ph), 95.1 (]C), 86.9 (C-1), 74.1 (C-4), 70.8
(C-3), 70.3 (C-2), 64.7 (C-5), 60.5, 60.3 (2COOCH2CH3), 21.8
(PheCH3), 20.5, 20.4 (COCH3), 14.5, 14.3 (2COOCH2CH3); HRFABMS:
calcd for C24H31NO12SNa: 580.1465. Found: 580.1465. Anal. Calcd
for C24H31NO12S: C, 51.70; H, 5.60; N, 2.51; S, 5.75. Found: C, 51.41;
H, 5.39; N, 2.58; S, 5.47%.
4.4.2. 2,3-Di-O-acetyl-N-(2,2-diethoxycarbonylvinyl)-4-O-mesyl-b-
D
-xylopyranosylamine (12). From 9; x¼4.60 g (10.1 mmol). Syrup
(4.13 g; 85%). [
a]
22 ꢀ35.7 (c 1.0, CH2Cl2); IR: nmax 3901, 3801, 3689,
D
4.3.1. N-(2,2-Diethoxycarbonylvinyl)-4-O-tosyl-
b
-
D
-xylopyranosyl-
3566, 1868, 1828, 1792, 1750, 1733, 1716, 1670, 1652, 1635, 1456,
amine (9). x¼4.00 g (12.5 mmol); y¼3.70 g (15.0 mmol); z¼2.90 g
1418, 1363, 1225, 1178, 1069 cmꢀ1 1H NMR: (500 MHz, CDCl3)
;
(15.0 mmol). Syrup (4.10 g; 87%). [
a
]
22 þ10.7 (c 1.0, CH2Cl2); IR: nmax
d
9.29 (dd, JNH,]CH¼13.0, JNH,1¼8.8 1H, NH), 8.0 (d,1H, HC]), 5.28 (t,
D
3848, 3737, 3649, 3568, 3649, 3451, 2332, 1865, 1842, 1737, 1713,
J2,3¼J3,4¼8.0, 1H, H-3), 4.97 (t, J1,2¼8.0, 1H, H-2), 4.71 (m, 1H, H-4),
4.54 (t, 1H, H-1), 4.26e4.16 (m, 2COOCH2CH3, H5a), 3.60 (dd,
J5a,5b¼12.0, J4,5b¼2.5, 1H, H-5b), 3.04 (s, 3H, OSO2CH3), 2.11, 2.03
(each s, each 3H, 2COCH3), 1.31, 1.28 (each t, each 3H,
1690, 1655, 1556, 1504, 1451 cmꢀ1 1H NMR: (500 MHz, CDCl3)
;
d
9.30 (dd, J NH,]CH¼13.4, JNH,1¼8.3, 1H, NH), 8.0 (d, 1H, HC]), 7.83,
7.81, 7.37, 7.35 (4H, Ph), 4.38 (m, 1H, H-4), 4.31 (t, J¼8.3, 1H, H-1),
4.24e4.14 (m, 2COOCH2CH3), 3.96 (dd, J5a, 5b¼11.8, J4,5a¼5.4, 1H, H-
5a), 3.72 (t, J2,3¼J3,4¼8.5, H-3), 3.47 (t, 1H, H-2), 3.41 (dd,
J4,5b¼1.5 Hz, 1H, H-5b), 2.45 (s, 3H, PheCH3) 1.30, 1.27 (each t, each
2COOCH2CH3); 13C NMR: (125.7 MHz, CDCl3)
d 169.7, 169.6, 167.9,
165.4 (4C]O), 157.4 (HC]), 95.2 (]C), 87.0 (C-1), 73.2 (C-4), 71.0
(C-3), 70.2 (C-2), 64.6 (C-5), 60.5, 60.3 (2COOCH2CH3), 38.5
(OSO2CH3), 20.7, 20.6 (2COCH3), 14.5, 14.3 (2COOCH2CH3);
HRFABMS: calcd for C18H28NO12S¼482.1332. Found: 482.1324.
3H, 2COOCH2CH3); 13C NMR: (125.7 MHz, CDCl3)
d 168.7, 165.8
(2C]O),158.1 (HC]),145.8,133.0,130.2,128.2 (Ph), 93.8 (]C), 88.4
(C-1), 77.0 (C-4), 74.4 (C-3), 73.1 (C-2), 64.8 (C-5), 60.5, 60.2
(2COOCH2CH3), 21.8 (PheCH3) 14.5, 14.3 (2COOCH2CH3);
HRFABMS: calcd for C20H27NO10SNa: 496.1253. Found: 496.1276.
4.4.3. 3,4-Di-O-acetyl-1,4-anhydro-N-(2,2-diethoxycarbonylvinyl)-
a-L-arabinopyranosylamina (13). To a stirred solution of the tosyl

J. Fuentes et al. / Tetrahedron 66 (2010) 9214e9222
9219
derivative 11 (3.00 g, 5.38 mmol) in hexamethyl phosphoramide
(HMPA) (25 mL) at 40 ꢂC in vacuum (20 mmHg), sodium methoxide
(0.35 g; 6.36 mmol) was added. After 40 min, the mixture was
poured into ice water (200 g) and extracted with ether (3ꢁ70 mL).
The organic layer was washed with brine, dried over MgSO4, fil-
tered, and concentrated to dryness. The residue was purified by
column chromatography (ether/hexane 3:2) to afford compound 13
IR: nmax 3901, 3869, 3853, 3837, 3819, 2960, 1918, 1868, 1844, 1828,
1791,1748,1716,1698,1684,1652,1635,1601,1558,1540,1520,1497,
1488, 1473, 1456, 1418, 1372, 1170, 1076 cmꢀ1; 1H NMR: (500 MHz,
CDCl3)
d 7.57 (s, 1H, HC]), 5.16 (br s, 1H, H-3), 5.04 (br s, 1H, H-4),
5.00 (br s, 1H, H-2), 4.36e4.08 (m, 4H, 2COOCH2CH3), 4.05 (t,
J¼5.9 Hz, 1H, H-5), 3.76e3.62 (m, 2H, H-6a, H6b), 3.44 (m, 2H,
OCH2(CH2)2CH3), 2.57 (br s, 1H, OH), 2.10, 2.09 (each s, each 3H,
COCH3), 1.51 (m, 2H, OCH2CH2CH2CH3), 1.36 (m, 2H,
OCH2CH2CH2CH3), 1.30, 1.25 (each t, each 3H, 2COOCH2CH3), 0.89 (t,
as an amorphous solid (1.40 g; 66%). [
a]
22 þ138 (c 1.0, CH2Cl2); IR:
D
nmax 3854, 3731, 3638, 2985, 2378, 2355, 2326, 1871, 1854, 1731,
1690, 1544, 1370, 1223, 1066 cmꢀ1
;
1H NMR: (500 MHz, CDCl3)
O(CH2)3CH3); 13C NMR: (125.7 MHz, CDCl3)
d 170.5, 169.4, 167.9,
d
7.51 (s,1H, HC]), 5.53 (d, J1,2¼2.5,1H, H-1), 4.78 (m,1H, H-2), 4.58
166.8 (4C]O), 146.3 (HC]), 99.3 (]C), 94.0 (C-2), 77.15 (C-3), 76.0
(C-4), 69.8 (C-5), 66.6 (OCH2(CH2)2CH3), 61.9 (C-6), 61.1, 60.6
(2COOCH2CH3), 31.6 (OCH2CH2CH2CH3), 20.95, 20.93 (2COCH3),
19.3 (OCH2CH2CH2CH3), 14.4, 14.2 (2COOCH2CH3), 13.9 (O
(CH2)3CH3); HRFABMS: calcd for C21H33NO10Na: 482.4981. Found:
482.4986.
(d, J2,3¼1.3, 1H, H-3), 3.82 (d, J4,5a¼3.8, 1H, H-4), 4.25, 4.19 (each q,
each 2H, JH,H¼7.0, 2COOCH2CH3), 3.68 (dd, 1H, J5a,5b¼7.9, H-5a),
3.63 (d, 1H, H-5b), 2.12, 2.09 (2s, COCH3), 1.30, 1.25 (each t, each 3H,
2COOCH2CH3); 13C NMR: (125.7 MHz, CDCl3)
d 170.7, 170.2, 166.3,
165.7 (4C]O), 146.0 (HC]), 103.1 (]C), 88.5 (C-1), 79.5 (C-2), 76.6
(C-3), 65.1 (C-5), 63.6 (C-4), 61.3, 60.8 (2COOCH2CH3), 20.9, 20.7
(COCH3), 14.4, 14.2 (2COOCH2CH3); HRFABMS: calcd for
C17H24NO9¼386.1451. Found: 386.1439.
Data for 18: (from a mixture 1:9 of compounds 15 and 18): syrup
(40 mg, 34%); 1H NMR: (500 MHz, CDCl3)
d 7.51 (s, 1H, HC]), 5.38
(dd, J3,4¼6.4, J4,5¼3.4, 1H, H-4), 5.13 (d, J2,3¼5.0 1H, H-2), 4.96 (dd,
1H, H-3), 4.30e3.95 (m, 4H, 2COOCH2CH3), 3.73e3.60 (m, 3H, H-5,
H6a, H6b), 3.40e3.25 (m, 2H, OCH2(CH2)2CH3), 2.97 (dd, JOH,6a¼4.2,
JOH,6b¼8.6, 1H, OH), 2.10, 2.09 (each s, each 3H, 2COCH3), 1.52 (m,
2H, OCH2CH2CH2CH3), 1.40 (m, 2H, OCH2CH2CH2CH3), 1.30, 1.25
(each t, each 3H, 2COOCH2CH3), 0.98 (t, 3H, O(CH2)3CH3); 13C NMR:
4.5. General procedure for the synthesis of compounds 14e20
To a stirred solution of compound 13 (x mg) in the corre-
sponding dry alcohol (methanol for 14 and 17, and butanol for 15
and 18) (y mL), over 4 A molecular sieves at rt, boron trifluoride
ꢁ
(125.7 MHz, CDCl3) d 171.3,170.4,167.2, 166.7 (4C]O),145.6 (HC]),
diethyl etherate (z
m
l) was added. After 1.0 h, the reaction mixture
98.0 (]C), 92.3 (C-2), 78.3 (C-4), 75.6 (C-3), 70.0 (OCH2(CH2)2CH3),
64.4 (C-5), 62.3 (C-6), 61.7, 60.7 (2COOCH2CH3), 31.5
(OCH2CH2CH2CH3), 21.0, 20.6 (2COCH3), 19.3 (OCH2CH2CH2CH3),
14.4, 14.1 (2COOCH2CH3), 13.8 [O(CH2)3CH3].
was neutralized by saturated aqueous NaHCO3 and then extracted
with ethyl acetate (2ꢁ50 mL). The organic layer was dried over
MgSO4, filtered, and concentrated to dryness. The residue was
purified by column chromatography (ethyl acetate/hexane 1:2).
4.5.3. (2S,3R,4R,5S)-3,4-Di-acetoxy-2-benzyloxy-N-(2,2-diethoxy-
carbonylvinyl)-5-hydroxymethylpyrrolidine (16) and (2R,3R,4R,5S)-
3,4-di-acetoxy-2-benzyloxy-N-(2,2-diethoxycarbonylvinyl)-5-hy-
droxymethylpyrrolidine (19). To a stirred solution of compound 13
4.5.1. (2S,3R,4R,5S)-3,4-Di-acetoxy-N-(2,2-diethoxycarbonylvinyl)-
5-hydroxymethyl-2-methoxypyrrolidine (14) and (2R,3R,4R,5S)-3,4-
di-acetoxy-N-(2,2-diethoxycarbonylvinyl)-5-hydroxymethyl-2-me-
ꢁ
thoxy pyrrolidine (17). x¼180 mg(0.47mmol); y¼10.0 mL; z¼200
m
l.
(100 mg; 0.26 mmol) in dry ether (10.0 mL), over 4 A molecular
Data for 14: syrup (102 mg, 52%). [
a
]
D
22 þ24 (c 1.1, CH2Cl2); IR: nmax
sieves at 0 ꢂC, boron trifluoride diethyl etherate (170
m
l) was added.
The color of the solution became white, and then benzyl alcohol
(500 l) was added. The reaction mixture was stirred at rt for 1.0 h,
3861, 3742, 2984, 1868,1791, 1742, 1693, 1605, 1372, 1230, 1716,
1074 cmꢀ1; 1H NMR: (500 MHz, CDCl3)
d
7.56 (s,1H, HC]), 5.20 (br s,
m
1H, H-3), 5.03 (br s, 1H, H-4), 4.93 (br s, 1H, H-2), 4.38e4.14 (m, 4H,
2COOCH2CH3), 4.02 (t, J¼6.0,1H, H-5), 3.72 (m, 2H, H-6a, H-6b), 3.30
(s, 3H, OCH3), 2.60 (1H, OH), 2.11, 2.10 (each s, each 3H, 2COCH3),1.31,
1.25 (each t, each 3H, 2COOCH2CH3); 13C NMR: (125.7 MHz, CDCl3)
neutralized with saturated aqueous NaHCO3, and extracted with
ethyl acetate (2ꢁ50 mL). The organic layer was dried over MgSO4,
filtered, and concentrated to dryness. The residue was purified by
column chromatography (ethyl acetate/hexane 1:2).
22
d
170.5,169.4,166.9,166.7 (4C]O),145.9 (HC]), 99.7 (]C), 94.6 (C-
Data for 16: syrup (80 mg, 62%). [
a
]
þ89 (c 1.0, CH2Cl2); IR:
D
2), 77.15 (C-3), 75.8 (C-4), 70.5 (C-5), 62.0 (C-6), 61.1, 60.6
(2COOCH2CH3), 53.9 (OCH3), 21.0, 20.9 (2COCH3), 14.5, 14.2
(2COOCH2CH3); HRFABMS: calcd for C18H28NO10¼418.1713. Found:
418.1721.
nmax 3901, 3819, 3710, 2982, 2918,1868,1844,1791,1748,1716,1684,
1652, 1635, 1602, 1558, 1488, 1473, 1418, 1371, 1232, 1168,
1071 cmꢀ1 1H NMR: (500 MHz, CDCl3)
; d 7.57 (s, 1H, HC]),
7.32e7.25 (5H, Ph), 5.19 (br s,1H, H-3), 5.16 (br s,1H, H-2), 5.07 (br s,
1H, H-4), 4.60 (s, 2H, CH2Ph), 4.30e3.90 (m, 4H, 2COOCH2CH3), 4.10
(t, J¼5.6, 1H, H-5), 3.76e3.65 (m, 2H, H-6a, H6b), 2.56 (br s, 1H, OH),
2.10, 2.06 (each s, each 3H, 2COCH3), 1.25, 1.20 (each t, each 3H,
2COOCH2CH3); 13C NMR: (125.7 MHz, CDCl3) 170.5, 169.5, 166.9,
166.7 (4C]O), 146.3 (HC]), 137.0, 128.5, 127.9, 127.7, 99.6 (]C),
93.8 (C-2), 77.6 (C-3), 76.2 (C-4), 69.7 (C-5), 68.7 (CH2Ph) 61.8 (C-6),
61.1, 60.6 (2COOCH2CH3), 20.9 (2COCH3), 14.4, 14.0 (2COOCH2CH3);
HRFABMS: calcd for C24H31NO10Na¼516.1846. Found: 516.1857.
Data for 17: syrup (67 mg, 34%). [
a
]
22 þ115 (c 1.0, CH2Cl2); IR: nmax
D
3853, 3749, 3674, 3648, 1733, 1698, 1652, 1635, 1616, 1558, 1540,
1520,1507,1456,1418,1236 cmꢀ1; 1H NMR: (500 MHz, CDCl3)
d 7.51
(s,1H, HC¼), 5.20 (dd, J3,4¼6.6, J4,5¼3.6,1H, H-4), 5.04 (d, J2,3¼4.8,1H,
H-2), 4.96 (dd, 1H, H-3), 4.30e4.13 (m, 4H, 2COOCH2CH3), 3.93 (dd,
J5,6a¼9.7,1H, H-5), 3.73e3.64 (m, 2H, H-6a, H-6b), 3.36 (s, 3H, OCH3),
2.95 (d, J¼7.2,1H, OH), 2.11, 2.10 (each s, each 1H, 2COCH3),1.30,1.25
(each t, each 3H, 2COOCH2CH3); 13C NMR: (125.7 MHz, CDCl3)
d
171.3, 170.4, 167.2, 166.6 (4C]O), 145.6 (HC]), 98.1 (]C), 93.2 (C-
Data for 19: syrup (26 mg, 20%). [
a
]
22 þ11 (c 1.0, CH2Cl2); IR: nmax
D
2), 77.9 (C-4), 75.5 (C-3), 64.5 (C-5), 62.5 (C-6), 61.7, 60.8
(2COOCH2CH3), 56.0 (OCH3), 21.0, 20.7 (2COCH3), 14.4, 14.1
(2COOCH2CH3); HRFABMS: calcd for C18H28NO10Na¼440.1532.
Found: 440.1548.
3853, 3837, 3749, 3628, 2982, 1868, 1844, 1828, 1792, 1748, 1698,
1652, 1602, 1558, 1540, 1507, 1488, 1473, 1456, 1366, 1069 cmꢀ1; 1H
NMR: (500 MHz, CDCl3) d 7.49 (s,1H, HC]), 7.37e7.27 (5H, Ph), 5.40
(dd, J3,4¼6.4, J4,5¼3.5, 1H, H-4), 5.24 (d, J2,3¼4.8, 1H, H-2), 5.00 (dd,
1H, H-3), 4.70 (d, Ja,b¼11.6, 1H, CHHPh), 4.46 (d, J¼11.6 Hz, 1H,
CHHPh), 4.31e4.13 (m, 4H, 2COOCH2CH3), 4.00 (m, 1H, H-5),
3.80e3.67 (m, 2H, H-6a, H6b), 2.90 (dd, JOH,H6a¼2.8, JOH,H6b¼9.6,1H,
OH), 2.11, 2.08 (each s, each 3H, 2COCH3), 1.31, 1.27 (each t, each 3H,
4.5.2. (2S,3R,4R,5S)-3,4-Di-acetoxy-2-butoxy-N-(2,2-diethoxy-
carbonylvinyl)-5-hydroxymethylpyrrolidine (15) and (2R,3R,4R,5S)-
3,4-di-acetoxy-2-butoxy-N-(2,2-diethoxycarbonylvinyl)-5-hydrox-
ymethylpyrrolidine (18). x¼100 mg (0.26 mmol); y¼10.0 mL;
2COOCH2CH3); 13C NMR: (125.7 MHz, CDCl3)
d
171.1, 170.1, 167.0,
z¼170
m
l. Data for 15: syrup (60 mg, 50%). [
a]
22 þ87 (c 1.1, CH2Cl2);
166.3 (4C]O), 145.3 (HC]), 135.6, 128.6, 128.3, 127.8, 97.8 (]C),
D

9220
J. Fuentes et al. / Tetrahedron 66 (2010) 9214e9222
90.9 (C-2), 77.9 (C-4), 75.2 (C-3), 64.1 (C-5), 70.1 (CH2Ph) 62.3 (C-6),
61.5, 60.2 (2COOCH2CH3), 20.8, 20.4 (2COCH3), 14.2, 13.8
(2COOCH2CH3); FABMS: m/e 516 [(MþNa)þ]; HRFABMS: calcd for
C24H31NO10Na¼516.1846. Found: 516.1857.
2COCH3), 1.34, 1.20 (each t, each 3H, 2COOCH2CH3), 1.20 (t, 3H,
SCH2CH3); 13C NMR: (125.7 MHz, CDCl3)
170.7, 169.8, 167.0,
d
166.5 (4C]O), 145.5 (HC]), 97.5 (]C), 76.9 (C-4), 74.9 (C-3),
71.6 (C-2), 65.1 (C-5), 61.3 (C-6), 60.4, 60.5 (2COOCH2CH3), 25.0
(SCH2CH3), 20.8, 20.6 (COCH3), 14.4, 14.2 (2COOCH2CH3), 14.0
(SCH2CH3); HRFABMS: calcd for C19H30NO9SNa¼470.1460. Found:
470.1469.
4.5.4. Cyclohexyl 2,3-di-O-acetyl-4-deoxy-4-diethoxycarbonylvinyla
mino-
0.26 mmol) in dry ether (10.0 mL), over 4 A molecular sieves at 0 C,
boron trifluoride diethyl etherate (220 l) was added. The color of
the solution became white, and then cyclohexanol (500 l) was
b-L-arabinopyranoside (20). To a stirred solution of 13 (0.10 g;
ꢂ
ꢁ
m
4.6.2. (2S,3R,4R,5S)-3,4-Di-acetoxy-2-butylthio-N-(2,2-diethoxy-
carbonylvinyl)-5-hydroxymethylpyrrolidine (22) and 3,4-di-acetoxy-2-
butylthio-(2R,3R,4R,5S)-N-(2,2-diethoxycarbonylvinyl)-5-hydroxy-
m
added. The reaction mixture was stirred at rt for 1.0 h, neutralized
with saturated aqueous NaHCO3, and extracted with ethyl acetate
(2ꢁ50 mL). The organic layer was dried over MgSO4, filtered, and
concentrated to dryness. The residue was purified by column
methylpyrrolidine (26). x¼100 mg (0.26 mmol); y¼8.0 mL; z¼170
ml;
w¼300
m
l. Data for 22: syrup (66 mg, 54%). [
a
]
22 þ13 (c 0.8, CH2Cl2);
D
1H NMR: (500 MHz, CDCl3)
d
7.72 (s, 1H, HC]), 5.38 (br s, 1H, H-3),
chromatography (diethyl ether/hexane 1:1) to afford compound 20
5.09 (br s, 1H, H-4), 4.89 (br s, 1H, H-2), 4.38e4.12 (m, 4H,
2COOCH2CH3), 4.02 (t, J5,6a¼J5,6b¼5.0 Hz, 1H, H-5), 3.76 (d, 2H, H-6a,
H6b), 2.56 (t, 2H, SCH2(CH2)2CH3), 2.40 (br s, 1H, OH), 2.11, 2.10 (each s,
each 3H, 2COCH3), 1.55 (m, 2H, SCH2CH2CH2CH3), 1.37 (m, 2H,
SCH2CH2CH2CH3), 1.32, 1.23 (each t, each 3H, 2COOCH2CH3), 0.9 (t, 3H,
22
as a syrup (70 mg; 55%). [
a
]
þ25 (c 1.0, CH2Cl2); IR: nmax 3372,
D
1744, 1686, 1656, 1607, 1433, 1372, 1316, 1224, 1153, 1061, 1025,
901 cmꢀ1 1H NMR: (500 MHz, CDCl3)
;
d
9.48 (dd, JNH,5¼9.8,
JNH,HC]¼13.6, 1H, NH), 7.84 (d, 1H, HC]), 5.27 (d, J2,3¼3.8, 1H, H-2),
5.30 (dd, 1H, J3,4¼10.6, J4,5¼4.0, H-4), 4.83 (dd, 1H, H-3), 4.26 (q, 1H,
COOCH2CH3), 4.21e4.14 (m, 3H, COOCH2CH3, H6a), 3.85 (ddd,
J5,6a¼10.9, J5,6b¼1.9, 1H, H-5), 3.67 (dd, J6a,6b¼12.3, 1H, H6b), 3.55
(m, 1H, OC6H11), 2.08, 2.04 (2s, COCH3), 1.82e1.68 (m, 5H, OC6H11),
1.51e130 (m, 5H, OC6H11), 1.31, 1.25 (each t, each 3H, 2COOCH2CH3);
S(CH2)3CH3); 13C NMR: (125.7 MHz, CDCl3)
d 170.4, 169.4, 166.9, 166.7
(4C]O), 147.0 (HC]), 99.3 (]C), 80.6 (C-3), 76.1 (C-4), 70.8 (C-2, C-5),
62.0 (C-6), 61.1, 60.6 (2COOCH2CH3), 31.6 (SCH2CH2CH2CH3), 30.1
(SCH2(CH2)2CH3), 22.2 (SCH2CH2CH2CH3), 20.7, 20.5 (2COCH3), 14.4,
14.2 (2COOCH2CH3), 13.7 (S(CH2)3CH3); HRFABMS: calcd for
C21H33NO9SNa¼498.1804. Found: 498.1773.
13C NMR: (125.7 MHz, CDCl3)
d 170.5, 170.3, 168.9, 166.0 (4C]O),
159.1 (HC]), 94.5 (C-2) 91.4 (]C), 76.4, 33.3, 31.4, 25.5, 23.8, 23.5
(OC6H11), 69.1 (C-3), 68.9 (C-4), 60.0 (C-6), 60.0, 59.7
(2COOCH2CH3), 57.4 (C-5), 20.7, 20.6 (COCH3), 14.4, 14.3
(2COOCH2CH3); HRFABMS: calcd for C23H36NO10¼486.2339.
Found: 486.2318.
Data for 26 (from a mixture 1:9 of compounds 22 and 26): syrup
(17 mg,14%); 1H NMR: (500 MHz, CDCl3)
d 7.58 (s,1H, HC]), 5.38 (m,
1H, H-4), 5.33 (m, 1H, H-3), 5.30 (m, 1H, H-2), 4.30e4.17 (m, 4H,
2COOCH2CH3), 3.99 (m, 1H, H-5), 3.83 (m, 1H, H-6a), 3.72 (m, 1H, H-
6b), 2.60 (m, 2H, SCH2(CH2)2CH3), 2.30 (br s,1H, OH), 2.13, 2.10 (each
s, each 3H, 2COCH3), 1.56 (m, 2H, SCH2CH2CH2CH3), 1.40 (m, 2H,
SCH2CH2CH2CH3) 1.32, 1.24 (each t, each 3H, 2COOCH2CH3), 0.91 (t,
4.6. General procedure for the synthesis of compounds 21e27
To a stirred solution of compound 13 (x mg) in dry ether (y mL),
3H, S(CH2)3CH3); 13C NMR: (125.7 MHz, CDCl3)
d 170.9, 169.9, 167.0,
166.0 (4C]O),145.7 (HC]), 99.0 (]C), 77.1 (C-4), 75.1 (C-3), 72.0 (C-
2), 65.3 (C-5), 61.5 (C-6), 61.6, 60.6 (2COOCH2CH3), 31.6
(SCH2CH2CH2CH3), 30.8 (SCH2(CH2)2CH3), 22.0 (SCH2CH2CH2CH3),
21.0, 20.5 (COCH3), 14.4, 14.2 (2COOCH2CH3), 13.7 (S(CH2)3CH3);
FABMS: m/e 498 [(MþNa)þ].
ꢁ
over 4 A molecular sieves at rt, boron trifluoride diethyl etherate
(z
corresponding thiol (ethanethiol for 21 and 25, butanethiol for 22
and 26, and butane-1,4-dithiol for 24) (w l) was added. After 1 h at
ml) was added. The color of solution became white, and then the
m
rt, the reaction mixture was neutralized with saturated aqueous
NaHCO3, and extracted by ethyl acetate (2ꢁ50 mL). The organic
layer was dried over MgSO4, filtered, and concentrated to dryness.
The residue was purified by column chromatography (ethyl acetate/
hexane 2:3).
4.6.3. (2S,3R,4R,5S)-3,4-Di-acetoxy-N-(2,2-diethoxycarbonylvinyl)-
5-hydroxymethyl-2-mercaptobutylpyrrolidine
(24). x¼100
mg
(0.26 mmol); y¼8.0 mL; z¼150 mL; w¼300 mL. Syrup (58 mg, 44%).
22
[a
]
þ12 (c 1.0, CH2Cl2); 1H NMR: (500 MHz, CDCl3)
d 7.70 (s, 1H,
D
HC¼), 5.37 (br s, 1H, H-3), 5.10 (br s, 1H, H-4), 4.90 (br s, 1H, H-2),
4.39e4.13 (m, 4H, 2COOCH2CH3), 4.01 (t, J5,6a¼J5,6a¼5.5, 1H, H-5),
3.76 (d, 2H, H-6a, H6b), 2.57 (t, 2H, SCH2(CH2)3SH), 2.52 (m, 2H,
SCH2CH2CH2CH2SH), 2.44 (1H, SH), 2.11, 2.10 (each s, each 3H,
2COCH3), 1.68 (m, 4H, SCH2(CH2)2CH2SH), 1.37 (m, 2H,
SCH2CH2CH2CH3), 1.32, 1.27 (each t, each 3H, 2COOCH2CH3); 13C
4.6.1. (2S,3R,4R,5S)-3,4-Di-acetoxy-N-(2,2-diethoxycarbonylvinyl)-
2-ethylthio-5-hydroxymethylpyrrolidine (21) and (2R,3R,4R,5S)-3,
4-di-acetoxy-N-(2,2-diethoxycarbonylvinyl)-2-ethylthio-5-hydroxy-
methylpyrrolidine (25). x¼180 mg (0.47 mmol); y¼10.0 mL;
z¼200
m
l; w¼500
m
l. Data for 21: syrup (93 mg, 58%). [
a
]
22 þ129 (c
D
1.0, CH2Cl2); IR: nmax 3901, 3819, 3710, 3628, 2928, 1918, 1868, 1844,
NMR: (125.7 MHz, CDCl3) d 170.3, 169.5, 166.9, 166.7 (4C]O), 146.9
1771, 1683, 1576, 1520, 1507, 1456, 1396, 1373, 1034 cmꢀ1; 1H NMR:
(HC]), 99.5 (]C), 80.7 (C-3), 76.1 (C-4), 70.8 (C-2, C-5), 62.0 (C-6),
61.2, 60.7 (2COOCH2CH3), 33.2 (HSCH2(CH2)3S), 29.8 (HS
(CH2)3CH2S), 27.7, 24.2 (SCH2CH2CH2CH2SH, SCH2CH2CH2CH2SH),
21.1, 21.0 (2COCH3), 14.5, 14.3 (2COOCH2CH3); HRFABMS: calcd for
C21H33NO9S2Na¼530.1494. Found: 530.1495.
(500 MHz, CDCl3) d 77.72 (s, 1H, HC]), 5.39 (br s, 1H, H-3), 5.10 (br
s, 1H, H-4), 4.91 (br s, 1H, H-2), 4.38e4.14 (m, 4H, 2COOCH2CH3),
4.02 (t, J¼5.2, 1H, H-5), 3.78 (m, 2H, H-6a, H6b), 2.60 (m, 2H,
SCH2CH3), 2.28 (1H, OH), 2.12, 2.11 (each s, each 3H, 2COCH3), 1.32,
1.27 (each t, each 3H, 2COOCH2CH3), 1.23 (t, 3H, SCH2CH3); 13C
NMR: (125.7 MHz, CDCl3)
d
170.4, 169.4, 166.9, 166.7 (4C]O), 147.0
4.6.4. (2S,3R,4R,5S)-3,4-di-acetoxy-N-(2,2-diethoxycarbonylvinyl)-
5-hydroxymethyl-2-p-tolylthiopyrrolidine (23) and (2R,3R,4R,5S)
-3,4-di-acetoxy-N-(2,2-diethoxycarbonylvinyl)-5-hydroxymethyl-2-
p-tolylthiopyrrolidine (27). To a stirred solution of compound 13
(280 mg; 0.73 mmol) in dry ether (10.0 mL), over 4 A molecular
sieves at rt, boron trifluoride diethyl etherate (300 ml) was added.
The color of solution became white, and then p-thiocresol (0.46;
3.7 mmol) in dry ether (2.0 mL) was added. After 1 h at rt, the re-
action mixture was neutralized with saturated aqueous NaHCO3 and
extracted by ethyl acetate (2ꢁ50 mL). The organic layer was dried
(HC]), 98.3 (]C), 79.7 (C-3), 75.1 (C-4), 69.7 (C-5, C-2), 61.0 (C-6),
60.1, 59.6 (2COOCH2CH3), 24.7 (SCH2CH3), 20.7, 20.5 (COCH3), 14.4,
14.2 (2COOCH2CH3), 13.3 (SCH2CH3); HRFABMS: calcd for
C19H30NO9S¼448.1641. Found: 448.1628.
ꢁ
Data for 25 (from a mixture 1:8 of compounds 21 and 25):
syrup (20 mg, 12%); 1H NMR: (500 MHz, CDCl3)
d
7.59 (s, 1H,
HC]), 5.38 (m, 1H, H-4), 5.33e5.30 (m, 2H, H-2, H-3), 4.30e4.17
(m, 4H, 2COOCH2CH3), 3.99 (m, 1H, H-5), 3.83 (m, 1H, H-6a), 3.72
(m, 1H, H-6b), 2.63 (m, 2H, SCH2CH3), 2.13, 2.10 (each s, each 3H,

J. Fuentes et al. / Tetrahedron 66 (2010) 9214e9222
9221
over MgSO4, filtered, and concentrated to dryness. The residue was
purified by column chromatography (ethyl acetate/hexane 1:2).
(C-5), 60.2 (C-6), 60.1, 60.0 (2COOCH2CH3), 20.9 (C6H4eCH3), 14.3
(2COOCH2CH3); HRFABMS: calcd for C20H28NO7S¼426.1586. Found:
426.1571.
22
Data for 23: syrup (234 mg, 63%). [
a
]
þ7 (c 0.8, CH2Cl2); 1H
D
NMR: (500 MHz, CDCl3)
d
7.61 (s, 1H, HC¼), 7.36, 7.35, 7.14, 7.12 (4H,
C6H4), 5.43 (br s, 1H, H-3), 5.20 (br s, 1H, H-2), 5.07 (br s, 1H, H-4),
4.24e3.98 (m, 4H, 2COOCH2CH3), 3.90 (br s, 1H, H-5), 3.76 (d,
J¼5.0 Hz, 2H, H-6a, H6b), 2.42 (br s,1H, OH), 2.32 (s, 3H, C6H4eCH3),
2.08, 2.02 (each s, each 1H, 2COCH3), 1.28e1.24 (m, 6H,
4.7.3. (7S,8R,9R,10S) 1-Aza-3-ethoxycarbonyl-8,9-dihydroxy-5-oxa-
4-oxo-10-(p-tolylthio)bicyclo[5,3,0]dec-2-ene (30). To a solution of
compound 23 (100 mg, 0.23 mmol) in methanol (y mL), Amberlite
IRA-400(HO) resin (1.0 g,10 equiv) was added. The reaction mixture
was stirred for 72 h at 40 ꢂC. The resin was collected and rinsed with
methanol, and the combined filtrates were evaporated to dryness.
The crude obtained was washed with ether (1 mL) and purified by
2COOCH2CH3); 13C NMR: (125.7 MHz, CDCl3)
d 170.4, 169.3, 166.9,
166.6 (4C]O), 146.6 (HC]), 139.2, 134.8, 130.8, 127.6 (C6H4), 100.0
(]C), 79.5 (C-3), 76.1 (C-4), 73.4 (C-2), 69.7 (C-5), 61.6 (C-6), 61.1,
60.7 (2COOCH2CH3), 21.8 (C6H4eCH3), 20.9, 20.7 (COCH3), 14.4, 14.2
(2COOCH2CH3); HRFABMS: calcd for C24H31NO9SNa¼532.1617.
column chromatography (CH2Cl2/MeOH 25:1). Amorphous solid
22
(70 mg; 80%). [
a]
ꢀ105 (c 0.5, CH2Cl2); 1H NMR: (500 MHz,
D
Found: 532.1611.
Data for 27: syrup (48 mg, 13%). [
NMR: (500 MHz, CDCl3)
CD3OD) d 7.93 (s, 1H, HC]), 7.42e7.45 (2H, C6H4), 7.19e7.27 (2H,
22
a
]
þ22 (c 0.9, CH2Cl2); 1H
C6H4), 4.82 (br s, 1H, H-10), 4.47 (dd, J6a, 6b¼13.0, J6a,7¼7.8, 1H, H-
6a), 4.42 (dd, J6b,7¼2.7, 1H, H-6b), 4.15 (q, 2H, COOCH2CH3), 3.87
(dd, J9,8¼6.9, J9,10¼6.3, 1H, H-9), 3.70 (dd, J7,8¼8.9, 1H, H-8), (ddd,
1H, H-7), 2.38 (s, 3H, C6H4eCH3), 1.24 (t, 3H, COOCH2CH3); 13C
D
d
7.06 (s, 1H, HC]), 7.38, 7.37, 7.17, 7.16 (4H,
C6H4), 5.47 (d, J2,3¼6.0, 1H, H-2), 5.40 (m, 1H, H-4), 5.34 (t, J3,4¼6.0,
1H, H-3), 4.23e4.03 (m, 4H, 2COOCH2CH3), 3.98 (br s, 1H, H-5), 3.84
(m, 1H, H-6a), 3.70 (m, 1H, H-6b), 2.34 (s, 3H, C6H4eCH3), 2.11, 2.05
(each s, each 1H, 2COCH3),1.29,1.17 (each t, each 3H, 2COOCH2CH3);
NMR: (125.7 MHz, CD3OD)
d 168.1, 166.7 (2C]O), 149.3 (HC]),
140.1, 135.7, 130.0, 126.3 (Ph), 91.3 (]C), 77.3 (C-9), 76.1 (C-10), 74.8
(C-8), 65.5 (C-7), 65.4 (C-6), 60.1 (OCH2Ph), 19.8 (PheCH3), 13.2
(COOCH2CH3); HRFABMS: calcd C18H22NO6S¼380.1168. Found:
380.1176.
13C NMR: (125.7 MHz, CDCl3)
d 170.9, 169.9, 167.0, 166.0 (4C]O),
145.3 (HC]), 139.6, 135.0, 130.4, 126.8 (C6H4), 97.7 (]C), 76.7 (C-4),
74.9 (C-3), 76.1 (C-2), 64.7 (C-5), 61.3 (C-6), 61.4, 60.2
(2COOCH2CH3), 21.2 (C6H4eCH3), 20.9, 20.5 (2COCH3), 14.2, 14.0
(2COOCH2CH3); HRFABMS: calcd for C24H31NO9SNa¼532.1617.
Found: 532.1635.
Supplementary data
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2010.09.065.
4.7. General procedure for the synthesis of compounds 28e30
To a solution of the corresponding O-protected thioglycoside (23
for 28 and 27 for 29) (x mg) in methanol (y mL), Amberlite IRA-400
(HO) resin (z mg) was added. The reaction mixture was stirred for
12 h at rt. The resin was collected and rinsed with methanol, and
the combined filtrates were evaporated to dryness. The crude
obtained was washed with ether (1 mL) and purified by column
chromatography (CH2Cl2/MeOH 25:1).
References and notes
€
1. See as examples: (a) Levy, D. E.; Fugedi, P. In The Organic Chemistry of Sugars;
CRC Taylor and Francis: London, 2006; (b) Nubbemeyer, U. Synthesis 2003,
961e1008.
2. See as examples: (a) Hoces, M. Eur. J. Org. Chem. 2003, 235e239; (b) Kunz, H.;
€
Ruck, K. Angew. Chem., Int. Ed. Engl. 1993, 105, 336e358 See also the book of
abstracts of ‘24th International Carbohydrate Symposium’, Oslo, Norway, 2008.
3. See as examples: (a) Compain, P.; Martin, O. R. Iminosugars: From Synthesis to
Therapeutic Applications; John Wiley and Sons, Ltd.: West Sussex, 2007; (b)
Afarinkia, K.; Bahar, A. Tetrahedron: Asymmetry 2005, 12, 1239e1287; (c) Lille-
lund, V. H.; Jensen, H.; Liang, X.; Bols, M. Chem. Rev. 2002, 102, 515e533; (d)
4.7.1. (2S,3R,4R,5S)-3,4-Dihydroxy-N-(2,2-diethoxycarbonylvinyl)-5-
hydroxymethyl-2-p-tolylthiopyrrolidine
(28). x¼150
mg
(0.28 mmol); y¼5.0 mL; z¼1.5 g (10 equiv). Amorphous solid
22
(100 mg; 85%). [
(CD3)2SO, 80 ꢂC)
a]
D
d
ꢀ14 (c 1.0, CH2Cl2); 1H NMR: (500 MHz,
€
Giannis, A. In Iminosugars as Glycosidase Inhibitors; Stutz, A. E., Ed.; Wiley-VCH:
Weinheim, 1999; Angew. Chem., Int. Ed. Engl. 1994, 33, 178e180.
7.75 (s, 1H, HC]), 7.31e7.30 (m, 2H, C6H4),
4. Butters, T. D.; Dwek, R. A.; Platt, F. M. Curr. Top. Med. Chem. 2003, 3, 561e574.
7.20e7.18 (m, 2H, C6H4), 5.60 (d, J3,OH-3¼5.3, 1H, OH-3), 5.1 (d, J4,OH-
ꢀ
5. (a) Bols, M.; Lopez, O.; Ortega-Caballero, F. In Comprehensive Glycoscience, from
Chemistry to System Biology; Kamerling, J. P., Ed.; Elsevier: 2007; Vol. I,
pp 815e884; (b) See also in Ref. 3a La Ferla, B.; Cipolla, L.; Nicotra, F, pp 25e58.
6. Fuentes, J.; Sayago, F. J.; Illangua, J. M.; Gasch, C.; Angulo, M.; Pradera, M. A.
Tetrahedron: Asymmetry 2004, 15, 603e615 and references therein.
7. Pradera, M. A.; Sayago, F. J.; Illangua, J. M.; Gasch, C.; Fuentes, J. Tetrahedron Lett.
2003, 44, 6605e6608.
8. Fuentes, J.; Gasch, C.; Olano, D.; Pradera, M. A.; Repetto, G.; Sayago, F. J. Tetra-
hedron: Asymmetry 2002, 13, 1743e1753 and references therein.
9. Natsume, M.; Wada, M. Chem. Pharm. Bull. 1975, 23, 2567e2572.
10. Natsume, M.; Wada, M. Chem. Pharm. Bull. 1976, 24, 2657e2660.
11. Altenbach, H. J.; Wischnat, R. Tetrahedron Lett. 1995, 36, 4983e4984.
12. Johnson, C.; Golebiowski, A.; Sundram, H.; Miller, M.; Dwaihy, R. Tetrahedron
Lett. 1995, 36, 653e654.
¼3.9, 1H, OH-4), 5.0 (d, J2,3¼3.9, 1H, H-2), 4.80 (br s, 1H, OH-5),
4
4.11e4.07 (m, 2H, COOCH2CH3), 4.0 (d, 1H, H-3), 3.90 (m, 2H,
COOCH2CH3), 3.80 (br s, 1H, H-4), 3.60 (m, 1H, H-6a), 3.50e3.47 (m,
2H, H-5, H-6b), 2.3 (s, 3H, C6H4eCH3), 1.22, 1.18 (each t, each 3H,
2COOCH2CH3); 13C NMR: (125.7 MHz, (CD3)2SO, 80 ꢂC)
d 166.7,
166.2 (2C]O),147.3 (HC]),138.0,133.5,130.1,129.5 (C6H4), 97.7 (]
C), 80.3 (C-3), 75.8 (C-4, C-2), 71.1 (C-5), 60.6 (C-6), 60.1, 59.7
(2COOCH2CH3), 21.0 (C6H4eCH3), 14.7, 14.4 (2COOCH2CH3);
HRFABMS: calcd for C20H28NO7S¼426.1586. Found: 426.1574.
13. Hankaas, M.; O’Doherty, G. Org. Lett. 2001, 3, 401e404.
14. Koulocheri, S.; Pitsinos, E.; Haroutounian, S. Synthesis 2002, 12, 1707e1710.
15. Fuchss, T.; Streicher, H.-J.; Schmidt, R. R. Liebigs Ann. Rec. 1997, 1315e1321.
16. Fuchss, T.; Schmidt, R. R. J. Carbohydr. Chem. 2000, 19, 677e691.
17. (a) Suzuki, K.; Hashimoto, H. Carbohydr. Res. 2000, 323, 14e27; (b) Suzuki, K.;
Hashimoto, H. Tetrahedron Lett. 1994, 35, 4119e4122.
4.7.2. (2R,3R,4R,5S)-3,4-Dihydroxy-N-(2,2-diethoxycarbonylvinyl)-5-
hydroxymethyl-2-p-tolylthiopyrrolidine (29). x¼80 mg (0.15 mmol);
22
y¼4.0 mL; z¼1.0 g (10 equiv). Syrup (50 mg; 79%). [
a
]
þ8 (c 1.0,
D
CH2Cl2); IR: nmax 3901, 3801, 3749, 3648, 3628, 2981, 1942, 1918,
1828, 1716, 1683, 1636, 1576, 1507, 1473, 1418, 1339, 1201, 1151,
18. Fuentes, J.; Illangua, J. M.; Sayago, F. J.; Angulo, M.; Gasch, C.; Pradera, M. A.
1069 cmꢀ1 1H NMR: (500 MHz, CDCl3)
; d 7.53 (s, 1H, HC]),
Tetrahedron: Asymmetry 2004, 15, 3783e3789.
19. Forrest, A. K.; Schmidt, R. R. Tetrahedron Lett. 1984, 25, 1769e1772.
20. Fuentes, J.; Olano, D.; Pradera, M. A. Tetrahedron: Asymmetry 1997, 8,
3443e3456.
21. Berges, D. A.; Fan, J.; Devinck, S.; Liu, N.; Dalley, N. K. Tetrahedron 1999, 55,
6759e6770 and references therein.
22. Fuentes, J.; Al Bujuq, N. R.; Angulo, M.; Gasch, C. Tetrahedron Lett. 2008, 49,
910e913.
23. Sayago, F. J.; Fuentes, J.; Angulo, M.; Gasch, C.; Pradera, M. A. Tetrahedron 2007,
63, 4695e4702.
7.40e7.38 (2H, C6H4), 7.20e7.16 (2H, C6H4), 5.50 (d, J3,OH-3¼5.3, 1H,
OH-3), 5.37 (d, J2,3¼5.5, 1H, H-2), 5.13 (d, J4,OH-4¼3.9 Hz, 1H, OH-4),
4.73 (br s, 1H, OH-5), 4.19e4.0 (m, 6H, 2COOCH2CH3, H-3, H-4),
3.67e3.61 (m, 2H, H-6a, H-5), 3.50e3.45 (m, 1H, H-6b), 2.31 (s, 3H,
C6H4eCH3), 1.20e1.18 (6H, 2COOCH2CH3); 13C NMR: (125.7 MHz,
(CD3)2SO, 80 ꢂC)
130.1, 129.5 (C6H4), 95.7 (]C), 77.2 (C-2), 76.5 (C-3), 76.3 (C-4), 86.5
d 166.6, 166.1 (2 C]O), 146.0 (HC]), 132.9, 130.5,

9222
J. Fuentes et al. / Tetrahedron 66 (2010) 9214e9222
24. Communicatedinparttothe‘EighthTetrahedronSymposium’Berlin,Germany,June
2007. See Fuentes, J.; Al Bujuq, N.R.; Pradera, M.A.; Gasch, C. Communication P343.
25. Stott, K.; Keeler, J.; Van, Q. N.; Shaka, A. J. J. Magn. Reson. 1997, 125, 302e324.
26. Gomez Sanchez, A.; Gomez Guillen, M.; Cert Ventula, A.; Scheidegger, U. An.
Quim., Ser. B 1968, 64, 579e590.
27. (a) For a review see Grindley, T. B. Adv. Carbohydr. Chem. Biochem. 1998, 53,
17e142; (b) See also Hanessian, S.; David, S. Tetrahedron 1985, 41, 643e663.
28. (a) Binkley, R. W. Adv. Carbohydr. Chem. Biochem. 1981, 38, 105e193; (b) Baer, H.
H.; Astles, D. J.; Chin, H. C.; Siemsen, L. Can. J. Chem. 1985, 63, 432e439.
29. Tsuda, Y.; Haque, M. E.; Yoshimoto, K. Chem. Pharm. Bull. 1983, 31, 1612e1624.
30. Tsuda, Y.; Nishimura, M.; Kobayashi, T.; Sato, Y.; Kanemitsu, K. Chem. Pharm.
Bull. 1991, 39, 2883e2887.
31. For selective monosulfonylation using dibutyltin oxide see Martinelli, M. J.;
Vaidyanathan, R.; Pawlak, J. M.; Nayyar, N. K.; Dhokte, U. P.; Doecke, C. W.;
ꢂ
Zollars, L. M.; Moher, E. D.; Khau, V. V.; Kosmrlj, B. J. Am. Chem. Soc. 2002, 124,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
3578e3585 and references therein.
ꢀ
ꢀ
32. Fuentes Mota, J.; Garcõa Fernandez, J. M.; Ortiz Mellet, C.; Pradera, M. A.; Ba-
biano Caballero, R. Carbohydr. Res. 1989, 188, 35e44.
33. Mizutani, K.; Kasai, R.; Nakamura, M.; Tanaka, O.; Matsuura, H. Carbohydr. Res.
1989, 185, 27e38.
34. Bock, K.; Pedersen, C. Adv. Carbohydr. Chem. Biochem. 1983, 41, 27e66.
35. Fuentes Mota, J.; Mostowicz, D.; Ortiz, C.; Pradera, M. A.; Robina, I. Carbohydr.
Res. 1994, 257, 305e316.
ꢀ
ꢀ
36. Gomez Sanchez, A.; Borrachero, P. Carbohydr. Res. 1984, 135, 101e106.