Cerium(IV)-mediated C-C bond formations in carbohydrate chemistry

Article abstract of DOI:10.1016/j.tet.2008.08.109

We provide a comprehensive study on the addition of radicals to unsaturated carbohydrates in the presence of cerium(IV) ammonium nitrate (CAN). The method is applicable to hexoses, pentoses, and disaccharides, tolerates different protecting groups, and is characterized by mild reaction conditions. Best substrates are malonates and glycals, which afford 2-C-branched carbohydrates in high yields and stereoselectivities. For the first time, the anomeric radicals were trapped with nucleophiles after oxidation and thus the 1- and 2-position of glucose were functionalized in one step. Nitro compounds are suitable CH acidic radical precursors as well, offering an easy access to C-analogs of glycosamines in moderate to good yields. Finally, selective reductions demonstrate the synthetic potential of cerium(IV)-mediated radical reactions in carbohydrate chemistry.

Full text of DOI:10.1016/j.tet.2008.08.109

Tetrahedron 64 (2008) 11925–11937
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Cerium(IV)-mediated C–C bond formations in carbohydrate chemistry
*
Elangovan Elamparuthi, Boo Geun Kim, Jian Yin, Michael Maurer, Torsten Linker
Department of Chemistry, University of Potsdam, Karl-Liebknecht-Strasse 24-25, D-14476 Potsdam/Golm, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
We provide a comprehensive study on the addition of radicals to unsaturated carbohydrates in the
presence of cerium(IV) ammonium nitrate (CAN). The method is applicable to hexoses, pentoses, and
disaccharides, tolerates different protecting groups, and is characterized by mild reaction conditions. Best
substrates are malonates and glycals, which afford 2-C-branched carbohydrates in high yields and
stereoselectivities. For the first time, the anomeric radicals were trapped with nucleophiles after oxi-
dation and thus the 1- and 2-position of glucose were functionalized in one step. Nitro compounds are
suitable CH acidic radical precursors as well, offering an easy access to C-analogs of glycosamines in
moderate to good yields. Finally, selective reductions demonstrate the synthetic potential of cerium(IV)-
mediated radical reactions in carbohydrate chemistry.
Received 10 July 2008
Accepted 8 August 2008
Available online 20 September 2008
Keywords:
Carbohydrates
C–C bond formations
Cerium(IV)
Radicals
Ó 2008 Elsevier Ltd. All rights reserved.
Synthetic methods
1. Introduction
offers a convenient entry point to biologically interesting C-glyco-
sides. Two selected examples are the amino acid analog 46 and the
Radical reactions have become a convenient and versatile tool in
organic synthesis during the last decades.1 Mild conditions and
high stereoselectivities have enabled numerous applications in
natural product chemistry, with special emphasis on carbon–car-
bon bond formations. The importance of radical reactions is
reflected in many reviews every year, and various new methodol-
ogies have been described very recently.2 For instance, the first
enantioselective organocatalysis in radical chemistry was pub-
lished merely one year ago.3
Despite such new developments, the generation of radicals from
alkyl halides and their addition to electron-poor alkenes in the
presence of tri-n-butylstannane is still one of the most prominent
methods for the formation of C–C bonds.1 The pioneering work of
Giese was essential for the understanding of orbital interactions in
radical reactions and led to many applications of the ‘tin hydride
method’.4 Exactly 25 years ago, the breakthrough in carbohydrate
chemistry was published by the same group, with the successful
C-disaccharide 5,7 available in one step from the same simple radical
precursor 1 (Scheme 1). The only disadvantage is the high toxicity of
AcO
O
AcO
CN
AcO
AcO
AcO
AcO
ax-3 (70%)
+
CN
O
2
AcO
H-SnBu3, h
Et2O, 35 °C
AcO
AcO
AcO
AcO
Br
O
1
CN
AcO
eq-3 (5%)
NHFmoc
AcO
AcO
O
NHFmoc
CO2Bn
CO2Bn
AcO
1
AcO
H-SnBu3, AIBN
synthesis of C-1 analogs 3 from acetobromo-
a-D-glucose (1) and
acrylonitrile (2) (Scheme 1).5
4 (73%)
Orbital interactions and a preferred boat-like conformation of the
anomeric radical are responsible for the remarkably high stereo-
selectivity. Additionally, the reactions are characterized by mild
conditions, good yields, and easily available starting materials, and
are nowadays well established in carbohydrate and natural product
chemistry. Especially the formation of C–C bonds at the 1-position
BnO
OBn
BnO
OBn
OBn
O
AcO
AcO
AcO
BnO
O
AcO
O
O
1
H-SnBu3, AIBN
5 (70%)
O
* Corresponding author. Tel.: þ49 331 977 5212; fax: þ49 331 977 5056.
E-mail address: linker@chem.uni-potsdam.de (T. Linker).
Scheme 1. Synthesis of C-glycosides 3–5 from easily available acetobromo-
glucose (1).
a-D-
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.08.109

11926
E. Elamparuthi et al. / Tetrahedron 64 (2008) 11925–11937
tin reagents, but silanes are suitable substitutes as hydrogen atom
donors.8
known for many years,15 this was the first example of a cerium(IV)-
mediated C–C bond formation in carbohydrate chemistry.
In contrast to the easy formation of carbon–carbon bonds at the
anomeric center via the ‘tin hydride method’, other positions of the
carbohydrate are more difficult to functionalize. For instance,
synthesis of the radical precursor 6 is tedious and the C-analogs 7
can only be isolated in moderate yields and steroeselectivities
(Scheme 2).9
AcO
AcO
MeO2C
AcO
CO2Me
O
O
AcO
MeO2C
OMe
CO2Me
CO2Me
8a
AcO
(10 equiv)
AcO
CO2Me
CAN
MeOH
0 °C
OMe
+
gluco-13a (62%)
manno-13a (14%)
+
AcO
AcO
AcO
O
O
AcO
AcO
AcO
O
AcO
AcO
AcO
OMe
CN
MeO2C
MeO2C
gluco-14a (16%)
CN
ONO2
10a
AcO
AcO
O
2
eq-7 (33%)
OMe
AcO
Scheme 4. Synthesis of 2-C-branched carbohydrates 13 and 14.
H-SnBu3, AIBN
+
Br
AcO
AcO
6
We were able to extend our methodology to other unsaturated
saccharides and malonates16 and very recently to benzyl-protected
glycals17 with even higher stereoselectivities. Furthermore, the
undesired formation of nitrates 14 was suppressed completely with
anhydrous cerium(IV) ammonium nitrate. We applied the addition
of malonates to 1-substituted glycals18 and in the total synthesis of
natural products.19 However, other CH acidic radical precursors
were less suitable for the synthesis of branched-chain carbohy-
drates, and we described the successful reaction with glycals in two
communications only recently.20
Herein we present a comprehensive study on the scope and
limitations of cerium(IV)-mediated C–C bond formations in carbo-
hydrate chemistry. For the first time, the anomeric radicals were
trapped with nucleophiles after oxidation. This enabled the func-
tionalization of the 1- and 2-position of glucose in only one step.
Nitro compounds were applied as CH acidic radical precursors,
which reacted less efficiently but provided high regio- and stereo-
selectivities. Thus, 2-C-branched carbohydrates with nitrogen sub-
stituents were isolated in moderate to good yields. Finally, the C-2
side-chains were modified by reductions, affording interesting
amines and amino acids, demonstrating the synthetic potential of
CAN-mediated radical reactions in carbohydrate chemistry.
CN
O
AcO
OMe
ax-7(13%)
Scheme 2. Synthesis of 2-C-branched carbohydrates 7.
More than 10 years ago, we developed a new entry to 2-C-
branched saccharides by a different strategy (Scheme 3). In this
case the carbohydrate is not the precursor, but the unsaturated
radical acceptor, with the advantage that such glycals 10 can be
easily synthesized on a large scale or are nowadays commercially
available.10 However, for a successful addition, the radicals 9 must
have electrophilic character due to the electron-rich double bond. If
this is the case, orbital interactions should favor the attack at the
2-position,4 affording 2-C-branched carbohydrates.
O
Mn+
- M(n-1)+
O
R
O
R
PGO
PGO
PGO
10
11
12
PG = Ac, Bn
MeOH - H
O
Mn+
OMe
R–H
8
R
9
PGO
- H+,
2. Results and discussion
R
13
- M(n-1)+
2.1. Malonates as radical precursors and nucleophilic
trapping at the anomeric center
Scheme 3. Concept for the synthesis of 2-C-branched carbohydrates 13.
The generation of electrophilic radicals 9 can be best accom-
plished by the oxidation of CH acidic precursors 8 (e.g., ketones,
malonates or nitro compounds) in the presence of manganese(III)
acetate or cerium(IV) ammonium nitrate (CAN). Besides reductive
methods,11 such oxidative transition-metal-mediated radical re-
actions have found many applications during the last two de-
cades.12 Another advantage is the subsequent oxidation of the
adduct radicals 11 into cations 12 under the reaction conditions,
directly affording glycosides 13 after trapping with the nucleophilic
solvent (Scheme 3).
The addition of dimethyl malonate (8a) to various glycals 10
proceeded efficiently in the presence of cerium(IV) ammonium ni-
trate (CAN) in methanol.14,16 Methyl glycosides 13 were isolated in
high yields and stereoselectivities by trapping of the intermediary
anomeric cations 12 with the nucleophilic solvent (Scheme 3). To
functionalize the 1- and 2-position in the same reaction step, the
radical addition had to be performedin anon-nucleophilic solvent in
the presence of an external nucleophile 15. However, CAN is only
soluble in polar solvents, which additionally influence the oxidation
potential of this transition-metal complex.1d,21 Thus, the generation
of malonyl radicals might have proceeded less efficiently, and
therefore the reaction conditions had to be carefully optimized.
We have been interested in transition-metal-mediated radical
reactions with simple precursors for many years.13 Our first suc-
cessful application of such reactions in carbohydrate chemistry was
We selected tri-O-acetyl- (10a) and tri-O-benzyl-D-glucal (10b)
the addition of dimethyl malonate (8a) to tri-O-acetyl-
D
-glucal (10a)
as suitable unsaturated radical acceptors, since they can be syn-
thesized on a large scale10 and afford gluco-configured addition
products, which represent biologically interesting 2-C-analogs.
Furthermore, the protecting groups can be easily removed after the
radical reactions. We tested a broad variety of nucleophiles 15, with
special emphasis on new pathways to disaccharides. First experi-
ments were conducted in water, to obtain the hemiacetals 16a
in the presence of CAN (Scheme 4).14 Ten equivalents of the pre-
cursor 8a were necessary for an efficient radical generation, but we
were able to remove the excess by distillation after complete con-
version. Importantly, the 2-C-analogs were obtained with exclusive
regioselectivity by an orbital controlled addition. Furthermore, the
methyl glycosides 13a and the nitrate 14a were isolated in high
yields and stereoselectivities in analytically pure form. Although the
addition of azide radicals to glycals in the presence of CAN was
(Table 1, entries 1 and 2). Although tri-O-acetyl-
D-glucal (10a) was
slightly soluble in this solvent, the oxidation potential of CAN was

E. Elamparuthi et al. / Tetrahedron 64 (2008) 11925–11937
11927
not sufficient to generate malonyl radicals and no conversion was
observed. On the other hand, we could not employ the O-benzyl-
protected carbohydrate 10b, which was completely insoluble in
water. Therefore, non-nucleophilic solvents were required, in order
to dissolve the carbohydrates and allow the external addition of
nucleophiles 15. N,N-Dimethylformamide (DMF) and acetonitrile
were applied in transition-metal-mediated radical reactions pre-
viously,12 and indeed, the addition of 25 equiv of water (15a)
afforded the hemiacetals 16a in moderate yields as anomeric
mixtures (entries 3–5). Acetonitrile was superior to DMF and was
employed in all further additions, with gluco/manno ratios in the
range from 4:1 to 5:1. These selectivities are independent from the
trapping nucleophile 15 and can be explained by unfavorable steric
interactions of the attacking malonyl radicals with the O-acetyl
group in the 3-position, in accordance to our previous studies.16
Next, we became interested in the synthesis of anomeric ace-
tates, since such compounds represent interesting glycosyl donors.
Acetic acid was not suitable as nucleophile, due to acid-catalyzed
Ferrier rearrangements.22 However, with potassium acetate (15b),
the requested 2-C-anologs 16b were isolated in moderate to good
yields (Table 1, entries 6 and 7). Interestingly, unsaturated carbo-
hydrates 17 were isolated as by-products, which can be rationalized
by the mechanism outlined in Scheme 5.
If a good nucleophile 15 is present (e.g., solvent methanol), the
intermediary cations 12 (compare Scheme 3) are trapped, affording
addition products 16. A neighboring group participation of the
malonyl side-chain is responsible for the exclusive formation of
b-glucosides and a-mannosides. On the other hand, if this bimole-
cular reaction is too slow (bad nucleophile and/or low concentra-
tions), deprotonation of the 2-position competes and elimination
products 17 are obtained in some reactions (Table 1). Glycosyl
Table 1
Addition of dimethyl malonate (8a) to glucals 10 in the presence of nucleophiles 15
PGO
PGO
PGO
PGO
MeO2C
PGO
CO2Me
PGO
PGO
O
O
PGO
O
CO2Me
CAN
solvent, 0 °C
O
PGO
Nu
PGO
+
+
+
PGO
PGO
CO2Me
8a
CO2Me
MeO2C
gluco-16
CO2Me
MeO2C
17
PG = Ac: 10a
PG = Bn: 10b
Nu
Nu 15
manno-16
Entry
Glycal
PG
Solvent
Nu 15 (equiv)
gluco/mannoa
gluco-16 (%)b
manno-16 (%)b
17 (%)b
1
2
3
4
5
6
7
8
10a
10b
10a
10a
10b
10a
10b
10a
10b
10a
10b
10b
10a
10b
10a
10a
Ac
Bn
Ac
Ac
Bn
Ac
Bn
Ac
Bn
Ac
Bn
Bn
Ac
Bn
Ac
Ac
H2O
H2O
DMF
d
dc
dc
5:1
5:1
5:1
4:1
4:1
df
d
d
d
de
12d
9d
10
13
d
11
12
14
9
d
d
d
d
d
24
18
d
d
d
d
d
16
10
d
32
d
d
15a:H2O (25)
15a:H2O (25)
15a: H2O (25)
15b: KOAc (10)
15b: KOAc (10)
15c: LiCl (10)
15d: EtOH (10)
15e: H17C8OH (10)
15e: H17C8OH (10)
15f: H25C12OH (10)
15g: i-PrOH (10)
15g: i-PrOH (10)
15h: PhCH2OH (10)
15i: t-BuOH (10)
26d
57d
56d
40
54
d
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
9
5:1
4:1
4:1
4:1
5:1
5:1
dg
5:1
68
59
64
53
51
68
d
10
11
12
13
14
15
16
12
9
d
de
21
OH
O
O
(5)
(5)
17
18
19
10a
10b
10a
Ac
Bn
Ac
CH3CN
CH3CN
CH3CN
15j:
15j:
15k:
O
5:1
5:1
5:1
31
29
7
5
6
28
31
35
O
O
O
OH
O
O
O
O
O
O
O
(5)
OH
de
O
O
O
O
O
O
(5)
20
10b
Bn
CH3CN
15k:
5:1
6
de
37
OH
O
a
Ratios determined by 1H NMR analysis of the crude product (300 MHz).
Yields of isolated products after column chromatography.
No conversion was observed.
b
c
d
e
f
Isolated as an anomeric mixture.
Due to the low yield, no manno isomer was isolated.
Addition of chlorine from oxidation of chloride by CAN.
Oxidation of benzyl alcohol (15h) to benzaldehyde by CAN.
g

11928
E. Elamparuthi et al. / Tetrahedron 64 (2008) 11925–11937
PGO
PGO
various glycals 10, affording carbohydrate C-analogs 13 and 14 in
O
good to excellent yields (Scheme 4).14,16–19 To gain access to further
functionalized 2-C-branched saccharides, we became interested in
radical precursors with nitro groups. Although the generation of
nitroalkyl radicals by oxidative transition-metal-mediated reactions
is known for many years,12,24 we published their application in car-
bohydrate chemistry in two communications only very recently.20
Hereinwe describe the synthetic and mechanistic details, explaining
the different product distributions and stereoselectivities.
PGO
Nu
CO2Me
MeO2C
PGO
PGO
H
Nu
- H
O
gluco-16
PGO
MeO2C
12
O
PGO
PGO
O
OMe
PGO
CO2Me
For the initial experiment, tri-O-acetyl-D-glucal (10a) and the
MeO2C
17
radical precursor ethyl nitroacetate (8b) were selected as com-
mercially available starting materials. The reaction was performed
in the presence of CAN in methanol as solvent. However, the
expected methyl glycosides 18a were isolated in only low yields as
complex mixtures of diastereomers together with the isoxazoline
N-oxides 19a. The formation of such bicyclic 2-C-branched carbo-
hydrates is interesting from a mechanistic point of view (Scheme
6). After the addition of the nitroalkyl radicals, the anomeric radical
11 is oxidized to the cations 12, and subsequent trapping by the
solvent affords the methyl glycosides 18a. Due to the generation of
three new stereocenters, a complex mixture of isomers results.
The isoxazoline N-oxides 19a are presumably formed via the
tautomersaci 12, whichcanattack theanomericcationandafford the
bicycles after deprotonation. Cyclization of the anomeric radical 11
by intramolecular attack of the nitro group and subsequent oxidation
might be possible as well, but the corresponding reaction of nitro-
methane (8c) did not give any bicyclic products at all (see below).
Scheme 5. Formation of the unsaturated carbohydrates 17.
chlorides 16c would be even more attractive glycosyl donors than
the acetates 16b, but lithium chloride (15c) was oxidized to chlorine
by CAN, which after addition to the double bond afforded 1,2-
dichlorides in low yields in accordance to the literature (entry 8).23
The reactions with alcohols as nucleophiles 15 proceeded very
efficiently and the 2-C-branched saccharides 16d–g were isolated
in moderate to good yields in analytically pure form (Table 1, en-
tries 9–14). Assembly of long chains at the anomeric center was
achieved with 1-octanol (15e) and 1-dodecanol (15f), affording
interesting amphiphilic carbohydrate structures. Even the sterically
more demanding 2-propanol (15g) was a suitable nucleophile. Al-
though glycal 17 was obtained as by-product, the isopropyl glyco-
sides 16g were isolated in 63–77% yield (entries 13 and 14). The
limit of trapping with alcohols was reached with benzyl alcohol
(15h), which was oxidized to benzaldehyde by CAN under the re-
action conditions (entry 15). Finally, tert-butanol (15i) afforded the
glycoside gluco-16i in only 21% yield and elimination to the glycal
17 was the major pathway (entry 16, Scheme 5), which can be
explained by unfavorable steric interactions.
AcO
AcO
AcO
AcO
O
NO2
CAN
MeOH
0 °C
O
+
AcO
EtO2C
AcO
CO2Et
NO2
Trapping of the intermediary cations 12 with another carbohy-
drate seemed to be very attractive, since disaccharides 16 would be
accessible in only one step. We investigated 1,2:3,4-di-O-iso-
10a
8b
11
CAN
AcO
AcO
propylidene-D-galactose (15j) and diacetone-D-glucose (15k) as
O
nucleophiles, which have only one reactive hydroxy group. Yields
with the sterically demanding secondary alcohol 15k were very
low, but the main gluco isomer 16k could be isolated (entries 19 and
20). The primary alcohol 15j reacted more efficiently, affording the
disaccharides 16j in moderate yields (entries 17 and 18). Since
malonates can be added to maltal and lactal as well,17b we estab-
lished a possibility to introduce carbon side-chains in the 2-posi-
tion of both sugar units of disaccharides in only one step.
In summary, we extended the scope of cerium(IV)-mediated C–
C bond formations in carbohydrate chemistry by simple function-
alization of the anomeric position. Acetonitrile was the ideal sol-
vent, providing sufficient solubility and allowing the generation of
malonyl radicals. The intermediary cations at the anomeric position
were trapped by external addition of nucleophiles, such as water,
acetate, and various alcohols. All reactions proceeded with high
AcO
NO2
EtO2C
12
MeOH
AcO
- H
AcO
AcO
AcO
AcO
O
O
O
AcO
AcO
EtO2C
AcO
OMe
NO2
- H
AcO
O
OH
EtO2C
N
N
O
EtO2C
18a (14%)
O
aci 12
19a (32%)
(gluco + manno)
(gluco + manno)
Scheme 6. Formation of the 2-C-branched carbohydrates 18 and 19.
To suppress the formation of methyl glycosides 18, which make
product separation much more difficult, we applied non-nucleo-
philic solvents. Best results were obtained with N,N-dime-
thylformamide (DMF), and the reactions proceeded smoothly with
various glycals 10 at 0 ꢀC. The isoxazoline N-oxides 19 were isolated
in moderate yields in analytically pure form, and the method was
suitable for hexoses, pentoses, and disaccharides (Scheme 7). The
exclusive formation of 1,2-cis-bicyclic products was established by
the coupling constants in the 1H NMR spectra and is due to the
intramolecular trapping of the anomeric cations. High to excellent
stereoselectivities at the 2-position were obtained as well, resulting
from an anti attack of the radicals to the 3-O-acetyl group, in ac-
cordance with the addition of malonates.16,17 Although yields of
isoxazoline N-oxides 19 are somewhat lower compared to other 2-
C-branched carbohydrates 13 or 16, the addition of ethyl nitro-
acetate (8b) to glycals 10 offers an easy one-step entry to unnatural
regio- and good stereoselectivities in favor of the
b-configured
gluco isomers. With less reactive nucleophiles, deprotonation at the
2-position competed, affording glycals as by-products. The
anomeric center was trapped with free OH groups of carbohydrates,
providing simple access to disaccharides in moderate yields. Al-
though radical reactions with CAN proceed in methanol more ef-
ficiently than in acetonitrile, we succeeded in the functionalization
of the 1- and 2-position of carbohydrates in one reaction step,
affording interesting C-analogs for further transformations.
2.2. Nitro compounds as radical precursors
The generation of radicals by cerium(IV) ammonium nitrate
(CAN) requires CH acidic precursors 8.12 In our previous studies, di-
methyl malonate (8a) was the best substrate for the addition to

E. Elamparuthi et al. / Tetrahedron 64 (2008) 11925–11937
11929
bicyclic carbohydrates, which can be transferred into interesting C-
glycosylated amino acids (Section 2.3).
Interestingly, selectivities at the newly formed stereocenter at
the 2-position are lower with nitromethane compared to malo-
nates or nitroesters. Thus, ribo, lyxo, epi-malto, and epi-lacto iso-
mers 20i–l were isolated as by-products (Scheme 8), whereas
precursors with two acceptor groups afforded exclusively the xylo-,
arabino-, malto-, and lacto-configured isoxazoline N-oxides 19
(Scheme 7). This can be rationalized by reduced steric interactions
between the attacking radicals and the functional groups at the
carbohydrate. Additionally, the nitromethyl radicals are less elec-
trophilic than malonyl radicals, resulting in an earlier transition
state and lower selectivities.
NO2
8b
O
CO2Et
+
O
EtO2C
N
CAN
AcO
EtO2C
+
O
O
DMF
0 °C
O
O
AcO
N
O
AcO
10
eq-19
ax-19
In summary, we were able to demonstrate the applicability of
CH acidic radical precursors with nitro groups in cerium(IV)-me-
diated C–C bond formations in carbohydrate chemistry. Ethyl
nitroacetate and nitromethane were suitable substrates for the
addition to various glycals, affording bicyclic isoxazoline N-oxides
or 2-C-nitromethyl-pyranosides in moderate to good yields. This
difference in product distribution was rationalized by an intra-
molecular trapping of the anomeric cations with the aci form of the
nitro compound, which should be interesting for the mechanism of
other transition-metal-mediated radical reactions.
gluco-19a (45%)a
galacto-19c (52%)a
xylo-19d (54%)a
–
manno-19a (13%)a
tri-O-acetyl-D-glucal (10a)
tri-O-acetyl-D-galactal (10c)
di-O-acetyl-D-xylal (10d)
di-O-acetyl-D-arabinal (10e)
hexa-O-acetyl-D-maltal (10f)
talo-19c (4%)a
–
arabino-19e (51%)a
–
malto-19f (64%)a
lacto-19g (53%)a
hexa-O-acetyl-D-lactal (10g)
–
a Yield of isolated pure product.
Scheme 7. Synthesis of isoxazoline N-oxides 19.
From the synthetic point of view, the additions of the new
radical precursors proceeded less efficiently than the established
reactions of malonates, but the convenient procedure allowed the
formation of C–C bonds and the introduction of nitro groups in only
one step. The regioselectivities were excellent, due to the electro-
philic character of the nitroalkyl radicals, and good to high ster-
eoselectivities were realized. The method was applicable to
hexoses, pentoses, and disaccharides and the glycal and nitro
alkane precursors are commercially available or can be synthesized
on a large scale. Finally, the nitro group allows various further
transformations like reductions to amino acids or amines (Section
2.3), and the 2-C-nitromethyl-pyranosides may even serve as pre-
cursors for the synthesis of C-disaccharides.25
The reaction of nitromethane (8c) with glycals 10 seemed to be
very attractive, since a C1 building block with an additional func-
tional group could be introduced at the 2-position by this radical
methodology. However, in comparison to dimethyl malonate (8a)
and ethyl nitroacetate (8b) the CH acidity of this reagent is lower.
Thus, the generation of radicals by CAN proceeds less efficiently and
is only possible under basic conditions.24 Therefore, O-acetylated
glycals were unsuitable substrates, due to the lability of the
functional groups. Very recently, we succeeded in the first
cerium(IV)-mediated C–C bond formation with nitromethane (8c)
in carbohydrate chemistry.20b Per O-benzylated glycals 10b,h–l
reacted smoothly at 0 ꢀC in the presence of potassium hydroxide as
base, and the 2-C-nitromethyl-pyranosides 20 were isolated in
moderate to good yields in analytically pure form (Scheme 8).
Pentoses 10i–j were oxidized by CAN to by-products, but the radical
addition worked well with disaccharides 20k,l. Interestingly, in
contrast to the reaction of ethyl nitroacetate (8b), nitromethane
(8c) afforded no bicyclic isoxazoline N-oxides. This result proves
the mechanism outlined in Scheme 6, with an intramolecular
trapping of the cation 12 and not of the radical 11. In a radical
pathway, both CH acidic precursors 8b and 8c would cyclize, which
is obviously not the case. Thus, the aci form of 12, which due to
the ester group is much more stabilized with 8c, is responsible for
the formation of isoxazoline N-oxides 19. During the addition of
nitromethane (8c) this tautomeric form is less favored, and thus
a cyclization cannot compete with the intramolecular reaction with
the solvent methanol, affording exclusively methyl glycosides 20.
2.3. Reduction of the nitro compounds
Nitro groups can be transferred into various other functional
groups and the reduction to amines is one of the most prominent
methods.26 However, only few applications in carbohydrate
chemistry exist, and the labile protecting groups and stereocenters
require mild reaction conditions. Very recently, we described the
reduction of the 2-C-nitromethyl-pyranosides 20 with lithium
aluminum hydride, which afforded O-benzyl-2-C-branched glyco-
samines.20b Catalytic hydrogenation was even more attractive,
since the protecting groups could be removed in the same reaction
step. Thus, after acetylation, the free C-2 branched glycosamines 21
were isolated in good yields in analytically pure form (Scheme 9).
Next, we became interested in the reduction of isoxazoline
N-oxides 19, since carbohydrate-linked unnatural amino acid de-
rivatives, which are stable toward enzymatic cleavage and possess
H3C NO2
8c
NO2
O
CAN
O
+
+
KOH, MeOH
0 °C
OMe
NO2
BnO
O
BnO
O
O
1. H2 (40 bar), Pd/C
2. Ac2O
OMe
NO2
BnO
OMe
OMe
NHAc
BnO
HO
10
ax-20
eq-20
20
gluco-20b
21
tri-O-benzyl-D-glucal (10b)
tri-O-benzyl-D-galactal (10h)
di-O-benzyl-D-xylal (10i)
di-O-benzyl-D-arabinal (10j)
hexa-O-benzyl-D-maltal (10k)
hexa-O-benzyl-D-lactal (10l)
gluco-20b (59%)a
manno-20b (12%)a
talo-20h (10%)a
gluco-21b (82%)a
galacto-21h (77%)a
xylo-21i (78%)a
galacto-20h (55%)a
xylo-20i (28%)a
ribo-20j (8%)a
galacto-20h
xylo-20i
arabino-20j
malto-20k
lacto-20l
lyxo-20i (20%)a
arabino-20j (31%)a
arabino-21j (75%)a
malto-21k (71%)a
lacto-21l (73%)a
malto-20k (58%)a epi-malto-20k (12%)a
lacto-20l (59%)a
epi-lacto-20l (9%)a
a Yield of isolated pure product.
a Yield of isolated pure product.
Scheme 9. Synthesis C-2 branched glycosamines 21.
Scheme 8. Synthesis of 2-C-nitromethyl-pyranosides 20.

11930
E. Elamparuthi et al. / Tetrahedron 64 (2008) 11925–11937
Table 2
Reduction of isoxazoline N-oxides 19 to C-glycosylated amino acids 22
O
O
O
1. H2 (80 bar),
Raney-Ni
OAc
NHAc
(R)-22
OAc
AcO
EtO2C
AcO
EtO2C
AcO
+
H
H
2. Ac2O,
pyridine
O
EtO2C
7
7
N
O
NHAc
(S)-22
19
Entry
Isoxazoline N-oxide
S:Ra
a
:
ba
(S)-22b
(R)-22b
1
2
3
4
5
6
gluco-19a
galacto-19c
xylo-19d
arabino-19e
malto-19f
lacto-19g
>95:5
>95:5
>95:5
<5:95
>95:5
>95:5
35:65
30:70
30:70
80:20
30:70
35:65
74
68
78
d
d
d
d
62
d
d
71
65
a
Ratios determined by 1H NMR analysis of the crude product (300 MHz).
Yields of isolated C-glycosylated amino acids 22. Main anomers were separated
b
by column chromatography and afforded analytically pure products.
Figure 2. X-ray crystal structure of the gluco isomer (S)-22a.20a
antibiotic activities,27 are potentially accessible in only one step.
However, two new stereogenic centers, at the anomeric position
exclusively from the Si face. Thus, all heterogenous reductions pro-
ceed from the convex side of bicycles 19, with excellent facial
selectivity.
and
a to the amino group, are formed during this transformation,
and thus the control of selectivity was a challenging task. Indeed, in
our previous studies, reduction with aluminum amalgam afforded
all four possible isomers.20a Therefore, we investigated catalytic
hydrogenations with various catalysts. Although Pd, Pd/C, PdO, and
Pd(OH)2 gave no conversion, Raney-Ni was the metal of choice and
after acetylation the C-glycosylated amino acids 22 were isolated in
moderate to good overall yield (Table 2). High pressure of hydrogen
gas was necessary, since the ethyl ester group reduces the reactivity
of the isoxazoline N-oxides and resulted in slow heterogenous
reactions.
Although
a and b anomers were easily distinguishable by the J1,2
coupling constant, the determination of the configuration at C-7
was more difficult. Comparison of NMR spectra clearly showed the
analogy of all S-configured products (S)-22 with small J2,7 coupling
constants of 1.2–1.7 Hz, whereas the R-configured arabino isomer
22e exhibits a remarkably larger coupling (J2,7¼8.5 Hz). However,
due to the fast rotation of the C–C single bond, the NMR data were
not completely indicative. Finally, we succeeded in the crystalli-
zation of the main gluco isomer 22a, which was assigned un-
equivocally as the S-configured product by X-ray analysis (Fig. 2).20a
In summary, reduction of the nitro compounds proceeded
smoothly by catalytic hydrogenation. The method was applicable to
hexoses, pentoses, and disaccharides. 2-C-Nitromethyl-pyranosides
afforded C-2 branched glycosamines in high yields, and the pro-
tecting groups were removed in the same reaction step. Isoxazoline
N-oxides were reduced by Raney-Ni in moderate yields but with
excellent stereoselectivities. This opened an easy entry to carbo-
hydrate-linked unnatural amino acid derivatives.
On the other hand, due to the steric hindrance of the carbohy-
drate residue, excellent R/S selectivities were obtained. The NMR
spectra of the crude products showed the exclusive formation of
one isomer at the newly formed stereocenter at C-7. Only a mixture
of
a and b anomers resulted after acetylation of the intermediary
hemiacetals. The main isomer of all C-glycosylated amino acids 22
had the 1,2-diequatorial configuration of substituents, which was
unequivocally proven by large coupling constants (J1,2 9–10 Hz) in
the 1H NMR spectra. Finally, the anomers were separated by
column chromatography and main products 22 were isolated in
analytically pure form.
3. Conclusions
Interestingly, most isoxazoline N-oxides 19 gave exclusively the
S-configured amino acids (S)-22, whereas arabino-19e reacted se-
lectively to (R)-22e (entry 4). This result is important from the
mechanistic point of view and can be rationalized by the preferred
configurations and conformations of the bicyclic starting materials
(Fig. 1).
The gluco, galacto, xylo, malto, and lacto isomers (eq-19a,c,d,f,g),
whichallhavethe C-2substituentequatoriallyaligned,wereattacked
by the catalyst exclusively from the Re face. Thus, the sugar ring ef-
ficiently shields one side of the isoxazoline, irrespective of the con-
figuration of the carbohydrate. On the other hand, arabino-19e is the
only isomerwithanaxial substituentat the2-position. Now the other
side of the isoxazoline is blocked and hydrogenation occurs
Cerium(IV)-mediated C–C bond formations are a valuable tool
for the synthesis of 2-C-branched carbohydrates. We investigated
the scope and limitations of such highly regioselective radical re-
actions, which are characterized by easily available precursors, mild
reaction conditions, and non-toxic reagents. For the first time, the
anomeric radicals were trapped with nucleophiles after oxidation
to cations by CAN. This enabled the functionalization of the 1- and
2-position of glucose in only one step. Furthermore, free OH groups
of carbohydrates were suitable external nucleophiles, providing
simple access to disaccharides in moderate yields. Nitro com-
pounds were applied as commercially available CH acidic radical
precursors, which reacted less efficiently but with high regio- and
stereoselectivities. Thus, nitromethane afforded 2-C-nitromethyl-
pyranosides, representing interesting substrates for the synthesis
of C-disaccharides. On the other hand, with ethyl nitroacetate, bi-
cyclic isoxazoline N-oxides were isolated in moderate to good
yields. This difference in product distribution was rationalized by
an intramolecular trapping of the anomeric cations with the aci
form of the nitro compound, which might be interesting for the
mechanism of other transition-metal-mediated radical reactions.
Finally, the C-2 side-chains of the carbohydrates were selectively
reduced by catalytic hydrogenation. 2-C-Nitromethyl-pyranosides
O
O
EtO2C
Re
N
AcO
O
O
AcO
O
EtO2C
N
O
Si
OAc
ax-19e
eq-19a,c,d,f,g
Figure 1. Facial selective hydrogenation of isoxazoline N-oxides 19.

E. Elamparuthi et al. / Tetrahedron 64 (2008) 11925–11937
11931
afforded C-2 branched glycosamines in high yields and the pro-
4.2.2. 3,4,6-Tri-O-benzyl-2-C-[bis-(methoxycarbonyl)-methyl]-D-
tecting groups were removed in the same step. Best conditions for
the reduction of isoxazoline N-oxides were found with Raney-Ni,
providing C-glycosylated amino acids in moderate yields but with
excellent stereoselectivities. This opened a convenient entry to
carbohydrate-linked amino acid derivatives, which are interesting
substrates for future applications in biology and medicine. Overall,
easily available starting materials, high selectivities, and few re-
action steps demonstrate the synthetic potential of CAN-mediated
radical reactions in carbohydrate chemistry.
glucal (benzyl-17)
20
Colorless syrup; Rf¼0.38 (cyclohexane/MTB 2:1); [
a]
þ 43.1 (c
D
0.90, CHCl3); 1H NMR (500 MHz, CDCl3):
d
¼3.49 (s, 3H, COOMe),
3.68 (dd, J¼10.7, 3.4 Hz, 1H, 6-H), 3.71 (s, 3H, COOMe), 3.81 (dd,
J¼10.7, 5.4 Hz,1H, 60-H), 3.94 (dd, J¼6.6, 5.1 Hz,1H, 4-H), 4.01 (s, 1H,
7-H), 4.24 (ddd, J¼9.7, 5.4, 3.4 Hz, 1H, 5-H), 4.40 (d, J¼5.1 Hz, 1H, 3-
H), 4.50 (d, J¼11.2 Hz, 1H, CH2–Ph), 4.55 (d, J¼11.5 Hz, 1H, CH2–Ph),
4.58 (d, J¼11.2 Hz,1H, CH2–Ph), 4.61 (d, J¼11.2 Hz,1H, CH2–Ph), 4.64
(d, J¼11.5 Hz, 1H, CH2–Ph), 4.74 (d, J¼11.5 Hz, 1H, CH2–Ph), 6.50 (s,
1H, 1-H), 7.22–7.34 (m, 15H, arom. H); 13C NMR (75 MHz, CDCl3):
4. Experimental
4.1. General
d
¼51.2 (d, C-7), 52.3, 52.4 (2q, COOMe), 68.0 (t, C-6), 72.4, 72.9, 73.4
(3t, CH2–Ph), 74.0, 74.8, 76.6 (3d, C-3, C-4, C-5), 106 (q, C-2), 127.6,
127.7, 127.8, 128.1, 128.2, 128.3, 128.4, 128.6, 128.9 (9d, arom. C-H),
137.8, 137.9, 138.1 (3s, arom. C–CH2O), 144.8 (d, C-1), 168.6, 169.0
All reactions were carried out under argon by using standard
Schlenk techniques. Solvents and commercially available chemicals
were purified by standard methods or used as purchased. Excess of
malonate was removed by a Kugelrohrofen (GKR-50, Bu¨chi). TLC
was performed on aluminum sheets silica gel 60F254 (Merck,
(2s, COOMe); IR (CDCl3):
n
¼3030, 2961, 1734, 1453, 1145, 1069, 736,
697, 600 cmꢂ1. Anal. Calcd (%) for C32H34O8 (546.61): C, 70.32; H,
6.27. Found: C, 70.30; H, 6.25.
4.3. General procedure for the synthesis of isoxazoline N-
Darmstadt). Silica gel (63–200
mm, Woelm, Erlangen) was used for
oxides 19
column chromatography. Optical rotations were measured on
a JASCO P-1020 polarimeter and melting points on a Bu¨chi SMP 20
apparatus (uncorrected). IR spectra were recorded on a Perkin–
Elmer 1600 FT-IR spectrometer. NMR spectra were recorded either
on a Bruker AM 250, AC 300, Avance 500 or DMX 600 with CDCl3 as
the solvent and internal standard. Elemental analyses were per-
formed on an ELEMENTAR Vario EL III analyser.
A solution of the per-O-acetylated-D-glycal 10 (3.0 mmol), ethyl
nitroacetate (8b) (3.99 g, 30 mmol, 10 equiv), and sodium hydrogen
carbonate (2.02 g, 24 mmol, 8 equiv) in DMF (10 mL) was cooled to
0 ꢀC under an argon atmosphere. At this temperature, a solution of
cerium(IV) ammonium nitrate (CAN) (9.87 g, 18 mmol, 6 equiv) in
DMF (20 mL) was added dropwise over a period of 4–6 h until TLC
showed complete conversion of the starting material. After stirring
for 30 min at 0 ꢀC, an ice-cold diluted solution of sodium thiosulfate
(50 mL) was added, and the mixture was extracted with dichloro-
methane (4ꢁ100 mL). The combined organic extracts were dried
(Na2SO4) and concentrated, and the excess of nitroacetate was re-
moved at 0.01 mbar in a Kugelrohrofen. The crude product was pu-
rified by column chromatography (cyclohexane/ethyl acetate) and
the isoxazoline N-oxides 19 were isolated in analytically pure form.
4.2. General procedure for the radical additions in the
presence of nucleophiles 15
A solution of tri-O-acetyl-
D-glucal (10a) (545 mg, 2.0 mmol) or
tri-O-benzyl- -glucal (10b) (830 mg, 2.0 mmol), dimethyl malonate
D
(8a) (2.64 g, 20 mmol, 10 equiv), sodium hydrogen carbonate
(670 mg, 8 mmol, 4 equiv), and the nucleophile 15 (5–25 equiv,
Table 1) in dry acetonitrile (10 mL) was cooled to 0 ꢀC under an
argon atmosphere. At this temperature, a solution of cerium(IV)
ammonium nitrate (CAN) (2.2–4.4 g, 2–4 equiv), which was dried in
a desiccator under high vacuum overnight, in acetonitrile (20 mL)
was added dropwise over a period of 4–6 h until TLC showed
complete conversion of the starting material. After stirring for
30 min at 0 ꢀC, an ice-cold diluted solution of sodium thiosulfate
(50 mL) was added, and the mixture was extracted with dichloro-
methane (4ꢁ100 mL). The combined organic extracts were dried
(Na2SO4) and concentrated, and the excess of malonate was re-
moved at 0.01 mbar in a Kugelrohrofen. The crude product was
purified by column chromatography (cyclohexane/ethyl acetate)
and the glycosides 16 were isolated in analytically pure form.
Complete characterization of all nucleophilic trapping products 16
is provided in Supplementary data. Elimination products 17 were
isolated in analytically pure form in the yields depicted in Table 1.
4.3.1. gluco-Isoxazoline N-oxide (gluco-19a)
Colorless syrup (545 mg, 45%); Rf¼0.47 (hexane/ethyl acetate
26
1:1); [
a]
ꢂ97.2 (c 1.03, CHCl3); 1H NMR (500 MHz, CDCl3):
¼1.34
d
D
(t, J¼7.1 Hz, 3H, CO2CH2CH3),1.99, 2.07, 2.11 (3s, 3H each, 3OAc), 4.00
(ddd, J¼7.0, 5.9, 3.3 Hz, 1H, 5-H), 4.07 (ddd, J¼8.3, 3.3, 1.4 Hz, 1H, 2-
H), 4.21 (dd, J¼12.0, 5.9 Hz, 1H, 6-H), 4.27 (dd, J¼12.0, 3.3 Hz,1H, 60-
H), 4.33(q, J¼7.1 Hz, 2H, CO2CH2CH3), 4.96 (ddd, J¼7.0, 2.0,1.4 Hz,1H,
4-H), 5.59 (dd, J¼3.3, 2.0 Hz,1H, 3-H), 6.05 (d, J¼8.3 Hz,1H,1-H); 13C
NMR (125 MHz, CDCl3):
d¼14.1 (q, CO2CH2CH3), 20.4, 20.6, 20.8 (3q,
3OAc), 43.2 (d, C-2), 62.2 (t, CO2CH2CH3), 63.6 (t, C-6), 66.6, 67.4, 69.1
(3d, C-3, C-4, C-5), 93.7 (d, C-1),106.7 (s, C-7), 157.9 (s, CO2Et),168.8,
169.0, 170.4 (3s, 3OAc); IR (neat):
n
¼2988, 1747, 1634, 1373, 1232,
1041, 876 cmꢂ1. Anal. Calcd (%) for C16H21NO11 (403.34): C, 47.65; H,
5.25; N, 3.47. Found: C, 47.82; H, 5.50; N, 3.32.
4.3.2. manno-Isoxazoline N-oxide (manno-19a)
4.2.1. 3,4,6-Tri-O-acetyl-2-C-[bis-(methoxycarbonyl)-methyl]-
glucal (acetyl-17)
D
-
Colorless oil (160 mg, 13%); Rf¼0.38 (hexane/ethyl acetate 1:1);
20
[a
]
þ19.0 (c 0.93, CHCl3); 1H NMR (300 MHz, CDCl3):
¼1.29 (t,
d
D
20
Colorless syrup; Rf¼0.37 (cyclohexane/ethyl acetate 1:1); [
a
]
J¼7.1 Hz, 3H, CO2CH2CH3), 2.03, 2.07, 2.11 (3s, 3H each, 3OAc), 3.95
(ddd, J¼6.9, 5.4, 2.7 Hz, 1H, 5-H), 4.18 (dd, J¼11.7, 6.9 Hz, 1H, 6-H),
4.25 (dd, J¼11.7, 5.4 Hz,1H, 60-H), 4.26 (q, J¼7.1 Hz, 2H, CO2CH2CH3),
4.23–4.32 (m, 1H, 2-H), 4.98 (dd, J¼4.6, 2.7 Hz, 1H, 4-H), 5.45 (dd,
J¼6.3, 4.6 Hz, 1H, 3-H), 5.79 (d, J¼6.7 Hz, 1H, 1-H); 13C NMR
D
þ58.9 (c 1.01, CHCl3); 1H NMR (600 MHz, CDCl3):
¼2.00, 2.06, 2.09
d
(3s, 3H each, OAc), 3.74, 3.75 (2s, 3H each, COOMe), 3.94 (s,1H, 7-H),
4.20 (dd, J¼12.2, 3.2 Hz,1H, 6-H), 4.31 (ddd, J¼7.6, 5.9, 3.2 Hz,1H, 5-
H), 4.39 (dd, J¼12.2, 5.9 Hz,1H, 60-H), 5.19 (dd, J¼7.6, 5.5 Hz,1H, 4-H),
5.71 (d, J¼5.5 Hz, 1H, 3-H), 6.64 (s, 1H, 1-H); 13C NMR (75 MHz,
(75 MHz, CDCl3):
45.1 (d, C-2), 62.3 (t, CO2CH2CH3), 63.6 (t, C-6), 64.9, 65.7, 74.9 (3d,
C-3, C-4, C-5), 93.4 (d, C-1), 105.8 (s, C-7), 158.3 (s, CO2Et), 168.9,
d
¼14.0 (t, CO2CH2CH3), 20.5, 20.6, 20.7 (3q, 3OAc),
CDCl3):
d
¼20.5, 20.6, 20.7 (3q, OAc), 47.9 (d, C-7), 52.7, 52.8 (2q,
COOMe), 61.2 (t, C-6), 67.2, 67.8 (2d, C-4, C-5), 73.8 (d, C-3), 103.9 (s,
C-2),146.6 (d, C-1),167.8,168.3,169.6,170.2,170.4 (5s, OAc, COOMe);
IR (CDCl3):
169.1, 170.5 (3s, 3OAc); IR (neat):
n
¼2988, 1746, 1638, 1376, 1236,
n
¼3065, 2986, 1752, 1664, 1425, 1286 cmꢂ1. Anal. Calcd
1048, 890 cmꢂ1. Anal. Calcd (%) for C16H21NO11 (403.34): C, 47.65; H,
5.25; N, 3.47. Found: C, 47.53; H, 5.42; N, 3.39.
(%) for C17H22O11 (402.40): C, 50.74; H, 5.51. Found: C, 50.46; H, 5.63.

11932
E. Elamparuthi et al. / Tetrahedron 64 (2008) 11925–11937
4.3.3. galacto-Isoxazoline N-oxide (galacto-19c)
J¼7.1 Hz, 2H, CO2CH2CH3), 4.11 (ddd, J¼8.3, 2.7, 1.4 Hz, 1H, 2-H),
4.34–4.46 (m, 1H, 5-H), 4.37 (dd, J¼12.2, 2.2 Hz, 1H, 60b-H), 4.38 (dd,
J¼10.8, 7.1 Hz,1H, 6a-H), 4.50 (dd, J¼10.8, 7.1 Hz,1H, 6b-H), 4.84 (dd,
J¼10.2, 4.1 Hz, 1H, 20-H), 4.98 (dd, J¼10.0, 9.6 Hz, 1H, 40-H), 5.17
(dd, J¼10.2, 9.6 Hz, 1H, 30-H), 5.20 (d, J¼4.1 Hz, 1H, 10-H), 5.54 (dd,
J¼2.7, 0.8 Hz, 1H, 3-H), 6.02 (d, J¼8.3 Hz, 1H, 1-H); 13C NMR
White crystals (630 mg, 52%); Rf¼0.36 (hexane/ethyl acetate
25
1:1); mp 140 ꢀC; [
CDCl3):
a
]
ꢂ27.8 (c 1.02, CHCl3); 1H NMR (500 MHz,
D
d
¼1.30 (t, J¼7.1 Hz, 3H, CO2CH2CH3), 2.05, 2.08, 2.17 (3s, 3H
each, 3OAc), 3.60 (ddd, J¼8.5, 6.2, 1.4 Hz, 1H, 2-H), 4.16 (d, J¼6.5 Hz,
2H, 6-H), 4.28 (q, J¼7.1 Hz, 2H, CO2CH2CH3), 4.42 (td, J¼6.5, 1.4 Hz,
1H, 5-H), 5.39 (dd, J¼8.5, 3.0 Hz, 1H, 3-H), 5.38–5.45 (m, 1H, 4-H),
(75 MHz, CDCl3):
d
¼14.0 (q, CO2CH2CH3), 20.4, 20.5, 20.6, 20.7, 20.8,
6.16 (d, J¼6.2 Hz, 1H, 1-H); 13C NMR (125 MHz, CDCl3):
d
¼14.1 (q,
20.9 (6q, 6OAc), 43.6 (d, C-2), 61.9 (t, CO2CH2CH3), 62.7, 63.4 (2t, C-
6, C-60), 68.1, 68.2, 68.5, 69.5, 69.6, 70.1, 76.9 (7d, C-3, C-4, C-5, C-20,
C-30, C-40, C-50), 93.2, 98.5 (2d, C-1, C-10), 105.8 (s, C-7), 158.1 (s,
CO2Et), 169.4, 169.5, 169.6, 170.3, 170.4, 170.5 (6s, 6OAc); IR (neat):
CO2CH2CH3), 20.4, 20.5, 20.6 (3q, 3OAc), 42.3 (d, C-2), 61.4 (t,
CO2CH2CH3), 62.3 (t, C-6), 64.4, 68.9, 70.4 (3d, C-3, C-4, C-5), 98.0 (d,
C-1), 112.7 (s, C-7), 158.4 (s, CO2Et), 169.6, 169.7, 170.4 (3s, 3OAc); IR
(neat):
n
¼2973, 1748, 1731, 1607, 1366, 1218, 1159, 1079, 1037,
n
¼2960, 1748, 1705, 1636, 1420, 1371, 1228, 1039 cmꢂ1. Anal. Calcd
890 cmꢂ1. Anal. Calcd (%) for C16H21NO11 (403.34): C, 47.65; H, 5.25;
N, 3.47. Found: C, 47.48; H, 5.20; N, 3.30.
(%) for C28H37NO19 (691.59): C, 48.63; H, 5.39; N, 2.03. Found: C,
48.41; H, 5.10; N, 2.28.
4.3.4. talo-Isoxazoline N-oxide (talo-19c)
4.3.8. lacto-Isoxazoline N-oxide (lacto-19g)
Colorless oil (50 mg, 4%); Rf¼0.34 (hexane/ethyl acetate 1:1);
White crystals (1.10 g, 53%); Rf¼0.37 (hexane/ethyl acetate 1:2);
25
27
[
a]
þ8.9 (c 0.97, CHCl3); 1H NMR (300 MHz, CDCl3):
d¼1.33 (t,
mp 200 ꢀC; [
d
a]
ꢂ35.0 (c 1.05, CHCl3); 1H NMR (300 MHz, CDCl3):
D
D
J¼7.1 Hz, 3H, CO2CH2CH3), 2.04, 2.07, 2.16 (3s, 3H each, 3OAc), 3.61
(dd, J¼8.1, 6.2 Hz, 1H, 2-H), 4.17 (dd, J¼6.4 Hz, 2H, 6-H), 4.30 (q,
J¼7.1 Hz, 1H, CO2CH2CH3), 4.31 (q, J¼7.1 Hz, 1H, CO2CH2CH3), 4.41
(td, J¼6.4, 1.2 Hz, 1H, 5-H), 5.39 (dd, J¼8.1, 3.3 Hz, 1H, 3-H), 5.42 (dd,
J¼3.3, 1.2 Hz, 1H, 4-H), 6.15 (d, J¼6.2 Hz, 1H, 1-H); 13C NMR
¼1.41 (t, J¼7.1 Hz, 3H, CO2CH2CH3), 1.96, 2.03, 2.04, 2.11, 2.12, 2.13
(6s, 3H each, OAc), 3.76 (ddd, J¼7.7, 1.5, 0.9 Hz, 1H, 4-H), 3.90 (ddd,
J¼7.7, 6.0, 2.8 Hz, 1H, 5-H), 3.98 (td, J¼6.8, 0.8 Hz, 1H, 50-H), 4.07
(ddd, J¼8.4, 2.9, 1.5 Hz, 1H, 2-H), 4.12 (dd, J¼12.1, 6.0 Hz, 1H, 6a-H),
4.15 (d, J¼6.8 Hz, 2H, 60-H), 4.24 (d, J¼12.0, 2.8 Hz, 1H, 6b-H), 4.38
(q, J¼7.1 Hz, 2H, CO2CH2CH3), 4.64 (d, J¼6.2 Hz, 1H, 10-H), 4.98 (m,
1H, 40-H), 5.01 (dd, J¼6.2, 2.9 Hz, 1H, 20-H), 5.37 (dd, J¼2.9, 0.8 Hz,
1H, 30-H), 5.87 (dd, J¼2.9, 0.9 Hz, 1H, 3-H), 6.00 (d, J¼8.4 Hz, 1H, 1-
(75 MHz, CDCl3):
42.4 (d, C-2), 61.4, 62.3 (2t, C-6, CO2CH2CH3), 64.4, 68.9, 70.5 (3d, C-
3, C-4, C-5), 89.5 (d, C-1), 98.0 (s, C-7), 158.3 (s, CO2Et), 169.7, 169.8,
d
¼14.1 (q, CO2CH2CH3), 20.5, 20.6, 20.7 (3q, 3OAc),
170.3 (3s, 3OAc); IR (neat):
n
¼2986, 1749, 1619, 1559, 1376, 1230,
H); 13C NMR (75 MHz, CDCl3):
d
¼14.1 (q, CO2CH2CH3), 20.3, 20.4,
1044, 925, 862 cmꢂ1. Anal. Calcd (%) for C16H21NO11 (403.34): C,
47.65; H, 5.25; N, 3.47. Found: C, 47.32; H, 5.07; N, 3.35.
20.5, 20.6, 20.7, 20.8 (6q, 6OAc), 43.5 (d, C-2), 60.8, 62.1, 63.7 (3t, C-
6, C-60, CO2CH2CH3), 66.9, 67.6, 68.6, 69.1, 70.9, 71.1, 75.8 (7d, C-3,
C-4, C-5, C-20, C-30, C-40, C-50), 93.4 (d, C-1), 102.0 (d, C-10), 106.0 (d,
C-7), 157.6 (s, CO2Et), 169.1, 169.2, 169.9, 170.0, 170.3, 170.5 (6s,
4.3.5. xylo-Isoxazoline N-oxide (xylo-19d)
Colorless oil (540 mg, 54%); Rf¼0.51 (hexane/ethyl acetate 1:1);
6OAc); IR (neat):
n
¼2984, 1748, 1641, 1568, 1422, 1373, 1235, 1136,
27
[
a
]
ꢂ118.8 (c 1.03, CHCl3); 1H NMR (300 MHz, CDCl3):
d
¼1.36 (t,
1063, 950, 911 cmꢂ1. Anal. Calcd (%) for C28H37NO19 (691.59): C,
48.63; H, 5.39; N, 2.03. Found: C, 48.44; H, 5.51; N, 1.85.
D
J¼7.1 Hz, 3H, CO2CH2CH3), 2.00, 2.14 (2s, 3H each, 2OAc), 3.81 (dd,
J¼13.1, 4.6 Hz, 1H, 5-H), 3.92 (ddd, J¼6.3, 2.8, 1.0 Hz, 1H, 2-H), 4.14
(dd, J¼13.1, 4.8 Hz,1H, 50-H), 4.35 (q, J¼7.1 Hz, 2H, CO2CH2CH3), 4.87
(dddd, J¼4.8, 4.6, 2.7, 1.0 Hz, 1H, 4-H), 5.74 (dd, J¼2.8, 2.7 Hz, 1H, 3-
4.4. General procedure for the radical addition of
nitromethane (8c)
H), 5.90 (d, J¼6.3 Hz, 1H, 1-H); 13C NMR (75 MHz, CDCl3):
¼14.1 (q,
d
CO2CH2CH3), 20.5, 20.7 (2q, 2OAc), 44.9 (d, C-2), 61.0 (t,
CO2CH2CH3), 62.2 (t, C-5), 65.2, 66.2 (2d, C-3, C-4), 93.4 (d, C-1),
106.4 (s, C-6), 158.3 (s, CO2Et), 168.9, 169.2 (2s, OAc); IR (neat):
A solution of the per-O-benzylated-D-glycal 10 (2.0 mmol), po-
tassium hydroxide (225 mg, 4.0 mmol, 2 equiv), and nitromethane
(8c) (1.22 g, 20 mmol, 10 equiv) in methanol (10 mL) was cooled to
0 ꢀC under an argon atmosphere. At this temperature, a solution of
cerium(IV) ammonium nitrate (CAN) (4.39 g, 8 mmol, 4 equiv) in
methanol (20 mL) was added dropwise over a period of 2 h until
TLC showed complete conversion of the starting material. After
stirring for 30 min at 0 ꢀC, an ice-cold diluted solution of sodium
bisulfate (50 mL) and ammonium chloride (20 mL) was added, and
the mixture was extracted with dichloromethane (3ꢁ100 mL). The
combined organic extracts were dried (Na2SO4) and concentrated.
The crude product was purified by column chromatography (cy-
clohexane/ethyl acetate), affording the 2-deoxy-2-C-nitromethyl-
pyranosides 20 in analytically pure form.
n
¼2988, 2942, 1754, 1628, 1374, 1234, 1063, 1044 cmꢂ1. Anal. Calcd
(%) for C13H17NO9 (331.28): C, 47.13; H, 5.17; N, 4.23. Found: C, 47.20;
H, 5.33; N, 4.02.
4.3.6. arabino-Isoxazoline N-oxide (arabino-19e)
Colorless oil (510 mg, 51%); Rf¼0.46 (hexane/ethyl acetate 1:1);
27
[
a]
þ49.6 (c 1.02, CHCl3); 1H NMR (300 MHz, CDCl3):
¼1.37 (t,
d
D
J¼7.1 Hz, 3H, CO2CH2CH3), 2.10, 2.12 (2s, 3H each, 2OAc), 3.79
(dd, J¼5.9, 5.7 Hz, 1H, 2-H), 3.93 (dd, J¼12.3, 5.6 Hz, 1H, 5-H), 4.07
(dd, J¼12.3, 3.9 Hz, 1H, 50-H), 4.33 (q, J¼7.1 Hz, 2H, CO2CH2CH3),
5.11 (ddd, J¼5.6, 3.9, 3.3 Hz,1H, 4-H), 5.76 (dd, J¼5.9, 3.3 Hz,1H, 3-H),
5.95 (d, J¼5.7 Hz, 1H, 1-H); 13C NMR (125 MHz, CDCl3):
¼14.0
d
(q, CO2CH2CH3), 20.6, 20.7 (2q, 2OAc), 45.5 (d, C-2), 61.9 (t,
CO2CH2CH3), 62.4 (t, C-5), 65.1, 66.4 (2d, C-3, C-4), 95.8 (d, C-1),108.8
4.4.1. Methyl 3,4,6-tri-O-benzyl-2-deoxy-2-C-nitromethyl-b-D-
glucopyranoside (gluco-20b)
(s, C-6), 158.3 (s, CO2Et), 169.6, 169.6 (2s, 2OAc); IR (neat):
n
¼2988,
Colorless oil (600 mg, 59%); Rf¼0.32 (cyclohexane/ethyl acetate
20
1748,1623,1377,1239,1093,1052,1017, 874 cmꢂ1. Anal. Calcd (%) for
C13H17NO9 (331.28): C, 47.13; H, 5.17; N, 4.23. Found: C, 47.01; H, 5.04;
N, 4.31.
2:1); [
a
]
þ10.4 (c 1.02, CHCl3); 1H NMR (500 MHz, CDCl3):
¼2.21
d
D
(dddd, J¼13.1, 11.2, 8.6, 4.4 Hz, 1H, 2-H), 3.37 (ddd, J¼11.3, 8.3,
4.3 Hz, 1H, 5-H), 3.40 (s, 3H, OMe), 3.54 (dd, J¼11.3, 2.4 Hz, 1H, 6-H),
3.62 (dd, J¼9.1, 4.3 Hz, 1H, 4-H), 3.65 (dd, J¼11.3, 2.3 Hz, 1H, 60-H),
3.68 (dd, J¼9.1, 8.6 Hz, 1H, 3-H), 4.29 (d, J¼8.6 Hz, 1H, 1-H), 4.44 (d,
J¼11.0 Hz, 1H, CH2–Ph), 4.45 (dd, J¼11.2, 5.8 Hz, 1H, 7-H), 4.46 (dd,
J¼12.6, 4.4 Hz, 1H, 70-H), 4.52 (d, J¼11.0 Hz, 1H, CH2–Ph), 4.54 (d,
J¼11.0 Hz, 1H, CH2–Ph), 4.56 (d, J¼12.0 Hz, 1H, CH2–Ph), 4.69
(d, J¼11.0 Hz, 1H, CH2–Ph), 4.83 (d, J¼11.0 Hz, 1H, CH2–Ph), 7.09–
4.3.7. malto-Isoxazoline N-oxide (malto-19f)
Colorless oil (1.33 g, 64%); Rf¼0.36 (hexane/ethyl acetate 1:2);
27
[
a]
ꢂ16.8 (c 1.02, CHCl3); 1H NMR (300 MHz, CDCl3):
¼1.38 (t,
d
D
J¼7.1 Hz, 3H, CO2CH2CH3), 1.97, 2.02, 2.03, 2.07, 2.10, 2.14 (6s, 3H
each, 6OAc), 3.65 (ddd, J¼7.9, 1.4, 0.8 Hz,1H, 4-H), 3.96 (ddd, J¼10.0,
5.0, 2.2 Hz, 1H, 50-H), 4.06 (dd, J¼12.2, 5.0 Hz, 1H, 60a-H), 4.11 (q,
7.26 (m, 15H, arom. H); 13C NMR (75 MHz, CDCl3):
d¼46.6 (d, C-2),

E. Elamparuthi et al. / Tetrahedron 64 (2008) 11925–11937
11933
57.1 (q, OMe), 68.6 (t, C-6), 72.1 (t, CH2–NO2), 73.5, 74.7 (2t, CH2–
Ph), 75.1 (d, C-3), 75.1 (t, CH2–Ph), 75.6, 79.6, 80.4, 101.9 (3d, C-4, C-
5, C-1), 127.6, 127.7, 127.8, 127.9, 127.9, 128.0, 128.4, 128.5, 128.6 (9d,
arom. C–H), 137.7, 137.8, 138.0 (3s, arom. C–CH2O); IR (neat):
959, 806, 733, 695, 601, 596 cmꢂ1. Anal. Calcd (%) for C29H33NO7
(507.58): C, 68.62; H, 6.55; N, 2.76. Found: C, 68.59; H, 6.82; N, 2.63.
4.4.5. Methyl 3,4-di-O-benzyl-2-deoxy-2-C-nitromethyl-b-D-
n
¼3030, 2914, 1555, 1496, 1453, 1380, 1209, 1093, 911, 738, 698, 617,
xylopyranoside (xylo-20i)
463 cmꢂ1. Anal. Calcd (%) for C29H33NO7 (507.58): C, 68.62; H, 6.55;
N, 2.76. Found: C, 68.49; H, 6.67; N, 2.80.
Colorless oil (220 mg, 28%); Rf¼0.41 (cyclohexane/ethyl acetate
20
2:1); [
a
]
D
þ45.7 (c 0.98, CHCl3); 1H NMR (500 MHz, CDCl3):
¼2.24
d
(dddd, J¼12.5, 10.5, 8.1, 4.5 Hz, 1H, 2-H), 3.25 (dd, J¼11.8, 5.8 Hz, 1H,
5-H), 3.46 (s, 3H, OMe), 3.57 (dd, J¼9.5, 8.1 Hz, 1H, 3-H), 3.66 (ddd,
J¼9.5, 5.8, 4.9 Hz, 1H, 4-H), 4.03 (dd, J¼11.8, 4.9 Hz, 1H, 50-H), 4.36
(d, J¼8.1 Hz, 1H, 1-H), 4.57–4.60 (m, 2H, 6-H, 60-H), 4.63 (d,
J¼11.5 Hz, 1H, CH2–Ph), 4.64 (d, J¼11.5 Hz, 1H, CH2–Ph), 4.67 (d,
J¼11.5 Hz, 1H, CH2–Ph), 4.94 (d, J¼11.5 Hz, 1H, CH2–Ph), 7.25–7.36
4.4.2. Methyl 3,4,6-tri-O-benzyl-2-deoxy-2-C-nitromethyl-a-D-
mannopyranoside (manno-20b)
Colorless oil (120 mg, 12%); Rf¼0.35 (cyclohexane/ethyl acetate
20
2:1); [
a
]
þ68.0 (c 1.00, CHCl3); 1H NMR (300 MHz, CDCl3):
¼2.76
d
D
(dddd, J¼13.7, 8.6, 4.6, 3.4 Hz, 1H, 2-H), 3.35 (s, 3H, OMe), 3.74 (ddd,
J¼11.3, 5.4, 4.5 Hz, 1H, 5-H), 3.81 (dd, J¼9.2, 5.4 Hz, 1H, 4-H,), 4.18
(dd, J¼9.2, 5.5 Hz, 1H, 3-H), 4.37 (dd, J¼13.3, 4.5 Hz, 1H, 6-H), 4.39
(d, J¼8.6 Hz, 1H, 1-H), 4.48 (dd, J¼13.3, 4.6 Hz, 1H, 60-H), 4.56 (d,
J¼12.0 Hz, 1H, CH2–Ph), 4.66 (d, J¼12.0 Hz, 1H, CH2–Ph), 4.68
(d, J¼12.0 Hz, 1H, CH2–Ph), 4.70 (d, J¼12.0 Hz, 1H, CH2–Ph), 4.74 (d,
J¼12.0 Hz, 1H, CH2–Ph), 4.79–4.83 (m, 2H, 7-H, 70-H), 4.93 (d,
J¼12.0 Hz, 1H, CH2–Ph), 7.16–7.4 (m, 15H, arom. H); 13C NMR
(m, 10H, arom. H); 13C NMR (75 MHz, CDCl3):
d
¼45.9 (d, C-2), 57.3
(q, OMe), 63.6 (t, C-5), 73.0 (t, CH2–NO2), 73.2, 75.1 (2t, CH2–Ph),
77.9, 79.8, 102.2 (3d, C-3, C-4, C-1), 128.2, 128.4, 128.4, 128.5, 128.9,
130.0 (m, arom. C–H), 138.2, 138.3 (2s, arom. C–CH2O); IR (film):
n
¼3030, 2875, 1552, 1453,1378, 1206,1070,1027, 997, 901, 734, 696,
620, 587 cmꢂ1. Anal. Calcd (%) for C21H25NO6 (387.43): C, 65.10; H,
6.50; N, 3.62. Found: C, 64.95; H, 6.61; N, 3.49.
(75 MHz, CDCl3):
d¼44.6 (d, C-2), 55.1 (q, OMe), 68.4 (t, C-6), 70.9
(d, C-3), 73.5 (t, CH2–NO2), 73.6, 74.8, 75.1 (3t, CH2–Ph), 77.8, 79.5,
98.0 (3d, C-4, C-5, C-1), 127.7, 127.7, 127.8, 127.8, 127.9, 128.0, 128.1,
128.4, 128.6 (m, arom. C–H), 137.7, 137.9, 137.9 (3s, arom. C–CH2O);
4.4.6. Methyl 3,4-di-O-benzyl-2-deoxy-2-C-nitromethyl-a-D-
lyxopyranoside (lyxo-20i)
Colorless oil (155 mg, 20%); Rf¼0.62 (cyclohexane/ethyl acetate
þ52.7 (c 0.99, CHCl3); 1H NMR (300 MHz, CDCl3):
¼2.65
d
20
IR (film):
n
¼3030, 2911, 1551, 1496, 1453, 1377, 1206, 1097, 1063,
2:1); [
a
]
D
988, 911, 734, 695, 675, 621, 572 cmꢂ1 Anal. Calcd (%) for C29H33NO7
(507.58): C, 68.62; H, 6.55; N, 2.76. Found: C, 68.51; H, 6.56; N, 2.48.
(dddd, J¼9.7, 8.4, 4.7, 3.3 Hz, 1H, 2-H), 3.34 (s, 3H, OMe), 3.56 (ddd,
J¼9.7, 8.2, 5.4 Hz, 1H, 4-H), 3.65 (dd, J¼9.7, 4.7 Hz, 1H, 3-H), 3.70
(dd, J¼8.2, 4.0 Hz, 1H, 5-H), 3.94 (dd, J¼5.4, 2.0 Hz, 1H, 50-H), 4.40
(dd, J¼13.4, 8.4 Hz, 1H, 6-H), 4.52 (d, J¼4.7 Hz, 1H, 1-H), 4.57 (dd,
J¼11.0, 3.3 Hz, 1H, 60-H), 4.65 (d, J¼11.5 Hz, 1H, CH2–Ph), 4.68 (d,
J¼11.5 Hz, 1H, CH2–Ph), 4.70 (d, J¼11.5 Hz, 1H, CH2–Ph), 4.94
(d, J¼11.5 Hz, 1H, CH2–Ph), 7.27–7.39 (m, 10H, arom. H); 13C NMR
4.4.3. Methyl 3,4,6-tri-O-benzyl-2-deoxy-2-C-nitromethyl-b-D-
galactopyranoside (galacto-20h)
White needles (560 mg, 55%); Rf¼0.54 (cyclohexane/ethyl ace-
20
tate 2:1); mp 127–128 ꢀC; [
(500 MHz, CDCl3):
a]
þ8.4 (c 0.98, CHCl3); 1H NMR
D
d
¼2.71 (dddd, J¼12.7, 9.3, 8.8, 4.1 Hz, 1H, 2-H),
(75 MHz, CDCl3):
CH2–NO2), 73.5, 74.9 (2t, CH2–Ph), 76.5, 79.2, 98.2 (3d, C-3, C-4, C-
d
¼44.0 (d, C-2), 57.2 (q, OMe), 60.3 (t, C-5), 72.8 (t,
3.50 (s, 3H, OMe), 3.56 (dd, J¼8.7, 5.9 Hz, 1H, 6-H), 3.59 (dd, J¼8.5,
5.6 Hz, 1H, 60-H), 3.63 (dd, J¼8.8, 2.3 Hz, 1H, 3-H), 3.69 (dd, J¼8.7,
5.6, 1.0 Hz, 1H, 5-H), 4.02 (dd, J¼2.3, 1.0 Hz, 1H, 4-H), 4.39 (d,
J¼11.5 Hz, 1H, CH2–Ph), 4.40 (d, J¼8.8 Hz, 1H, 1-H), 4.43 (d, J¼11.5,
Hz, 1H, CH2–Ph), 4.44 (d, J¼11.5 Hz, 1H, CH2–Ph), 4.49 (d, J¼11.5 Hz,
1H, CH2–Ph), 4.58 (d, J¼11.5 Hz,1H, CH2–Ph), 4.70–4.73 (m, 2H, 7-H,
70-H), 4.86 (d, J¼11.5 Hz, 1H, CH2–Ph), 7.27–7.37 (m, 15H, arom. H);
1), 127.7, 127.8, 128.0, 128.0, 128.4, 128.5 (m, arom. C–H), 137.9, 138.0
(2s, arom. C–CH2O); IR (neat):
n
¼3030, 2932,1550,1453,1377,1265,
1204, 1092, 1045, 1027, 952, 735, 696 cmꢂ1. Anal. Calcd (%) for
C21H25NO6 (387.43): C, 65.10; H, 6.50; N, 3.62. Found: C, 64.97; H,
6.42; N, 3.29.
13C NMR (75 MHz, CDCl3):
d
¼42.3 (d, C-2), 57.4 (q, OMe), 69.1 (t, C-
4.4.7. Methyl 3,4-di-O-benzyl-2-deoxy-2-C-nitromethyl-a-D-
arbinopyranoside (arabino-20j)
6), 71.0 (d, C-3), 72.2 (t, CH2–NO2), 72.6 (t, CH2–Ph), 73.9 (d, C-4),
74.0, 74.9 (2t, CH2–Ph), 78.3, 102.0 (2d, C-5, C-1), 128.0, 128.2, 128.3,
128.4, 128.5, 128.6, 128.9, 130.0 (m, arom. C–H), 138.0, 138.3, 138.6
White crystals (240 mg, 31%); Rf¼0.41 (cyclohexane/ethyl ace-
20
tate 2:1); mp 128 ꢀC; [
CDCl3):
a
]
D
ꢂ46.1 (c 1.01, CHCl3); 1H NMR (300 MHz,
(3s, arom. C–CH2O); IR (KBr):
n
¼3031, 2862, 1549, 1495, 1451, 1352,
d
¼2.72 (dddd, J¼15.5, 12.5, 8.5, 4.1 Hz, 1H, 2-H), 3.31 (dd,
1205, 1159, 1095, 1066, 1025, 1000, 910, 750, 696, 640, 596 cmꢂ1
.
J¼13.0, 1.0 Hz, 1H, 5-H), 3.51 (s, 3H, OMe), 3.58 (dd, J¼8.5, 2.7 Hz,
1H, 3-H), 3.75 (ddd, J¼2.7, 2.2, 1.0 Hz, 1H, 4-H), 4.19 (dd, J¼13.0,
2.2 Hz, 1H, 50-H), 4.35 (d, J¼11.2 Hz, 1H, CH2–Ph), 4.36 (d, J¼8.5 Hz,
1H, 1-H), 4.54 (d, J¼11.2 Hz, 1H, CH2–Ph), 4.63 (d, J¼12.3 Hz, 1H,
CH2–Ph), 4.70 (dd, J¼12.9, 4.1 Hz, 1H, 6-H), 4.74 (dd, J¼12.5, 4.9 Hz,
1H, 60-H), 4.75 (d, J¼12.3 Hz, 1H, CH2–Ph), 7.27–7.40 (m, 10H, arom.
Anal. Calcd (%) for C29H33NO7 (507.58): C, 68.62; H, 6.55; N, 2.76.
Found: C, 68.59; H, 6.51; N, 2.77.
4.4.4. Methyl 3,4,6-tri-O-benzyl-2-deoxy-2-C-nitromethyl-a-D-
talopyranoside (talo-20h)
Colorless oil (100 mg, 10%); Rf¼0.62 (cyclohexane/ethyl acetate
H); 13C NMR (75 MHz, CDCl3):
d
¼42.4 (d, C-2), 57.4 (q, OMe), 63.8 (t,
20
2:1); [
a
]
þ26.5 (c 1.00, CHCl3); 1H NMR (300 MHz, CDCl3):
d¼3.01
C-5), 69.9 (d, C-3), 71.5, 71.5 (2t, CH2–Ph), 72.5 (t, CH2–NO2), 76.4,
102.3 (2d, C-4, C-1), 128.2, 128.4, 128.4, 128.8, 128.9 (m, arom. C–H),
138.2, 138.4 (2s, arom. C–CH2O); IR (KBr):
1380, 1350, 1255, 1225, 1122, 1093, 1001, 878, 796, 740, 696, 649,
619, 564, 492, 425 cmꢂ1. Anal. Calcd (%) for C21H25NO6 (387.43): C,
65.10; H, 6.50; N, 3.62. Found: C, 65.12; H, 6.58; N, 3.66.
D
(dddd, J¼9.5, 8.7, 5.2, 4.2 Hz, 1H, 2-H), 3.37 (s, 3H, OMe), 3.61 (dd,
J¼9.3, 6.4 Hz, 6-H), 3.66 (dd, J¼9.3, 6.5 Hz, 1H, 60-H), 3.85 (dd, J¼2.7,
1.2 Hz, 1H, 4-H), 3.94 (ddd, J¼7.5, 6.5, 1.2 Hz, 1H, 5-H), 4.06 (dd,
J¼5.2, 2.7 Hz, 1H, 3-H), 4.47 (d, J¼12.0 Hz, 1H, CH2–Ph), 4.52
(d, J¼11.3 Hz, 1H, CH2–Ph), 4.56 (d, J¼12.0 Hz, 1H, CH2–Ph), 4.61 (d,
J¼12.0 Hz, 1H, CH2–Ph), 4.70 (d, J¼12.0 Hz, 1H, CH2–Ph), 4.80–4.83
(m, 2H, 7-H, 70-H), 4.84 (d, J¼8.7 Hz, 1H, 1-H), 4.85 (d, J¼11.3 Hz, 1H,
CH2–Ph), 7.26–7.40 (m, 15H, arom. H); 13C NMR (75 MHz, CDCl3):
n
¼3029, 2867, 1535,1453,
4.4.8. Methyl 3,4-di-O-benzyl-2-deoxy-2-C-nitromethyl-b-D-
ribopyranoside (ribo-20j)
d
¼40.9 (d, C-2), 55.6 (q, OMe), 69.4 (t, C-6), 69.7 (d, C-3), 71.2 (t,
Colorless oil (60 mg, 8%); Rf¼0.54 (cyclohexane/ethyl acetate
20
CH2–NO2), 73.8, 74.0 (2t, CH2–Ph), 74.3, 74.4 (2d, C-4, C-5), 75.3 (t,
CH2-Ph), 100.1 (d, C-1), 127.8, 128.1, 128.2, 128.2, 128.3, 128.8, 128.8,
130.0 (m, arom. C–H), 138.1, 138.4, 138.7 (3s, arom. C–CH2O); IR
2:1); [
a]
ꢂ60.7 (c 0.98, CHCl3); 1H NMR (300 MHz, CDCl3):
¼2.86
d
D
(dddd, J¼10.3, 7.8, 4.8, 2.8 Hz, 1H, 2-H), 3.38 (s, 3H, OMe), 3.69 (dd,
J¼5.8, 2.2 Hz, 1H, 5-H), 3.74 (ddd, J¼3.4, 2.2, 1.0 Hz, 1H, 4-H), 3.82
(dd, J¼12.1, 3.4 Hz, 1H, 50-H), 4.03 (dd, J¼7.8, 1.0 Hz, 1H, 3-H), 4.58
(neat):
n
¼3030, 2910, 1547, 1496, 1453, 1357, 1205, 1096, 1051, 1026,

11934
E. Elamparuthi et al. / Tetrahedron 64 (2008) 11925–11937
(d, J¼12.0 Hz, 1H, CH2–Ph), 4.62–4.68 (m, 2H, 6-H, 60-H), 4.69 (d,
J¼12.0 Hz, 1H, CH2–Ph), 4.73 (d, J¼12.0 Hz, 1H, CH2–Ph), 4.75 (d,
J¼12.0 Hz, 1H, CH2–Ph), 4.78 (d, J¼4.8 Hz, 1H, 1-H), 7.27–7.40 (m,
4.4.11. Methyl 3,6,8,9,10,12-hexa-O-benzyl-2-deoxy-2-C-
nitromethyl- -lactopyranoside (lacto-20l)
b-D
Colorless oil (1.11 g, 59%); Rf¼0.51 (cyclohexane/ethyl acetate
20
10H, arom. H); 13C NMR (75 MHz, CDCl3):
d
¼41.7 (d, C-2), 55.6 (q,
2:1); [
a
]
þ8.1 (c 1.01, CHCl3); 1H NMR (300 MHz, CDCl3):
¼2.13
d
D
OMe), 60.9 (t, C-5), 71.6 (t, CH2–NO2), 72.0 (t, CH2–Ph), 72.5 (d, C-3),
73.3 (t, CH2–Ph), 73.9, 99.8 (2d, C-4, C-1), 127.5, 127.6, 127.7, 127.8,
128.5, 128.5 (m, arom. C–H), 137.9, 138.1 (2s, arom. C–CH2O); IR
(dddd, J¼15.3, 12.7, 8.4, 4.1 Hz, 1H, 2-H), 3.27 (dd, J¼11.3, 3.4 Hz, 1H,
12-H), 3.29 (dd, J¼6.8, 2.4 Hz, 1H, 4-H), 3.32 (ddd, J¼6.8, 4.4, 1.4 Hz,
1H, 5-H), 3.42 (s, 3H, OMe), 3.40–3.52 (m, 1H, 11-H), 3.58 (dd,
J¼11.3, 8.5 Hz, 1H, 120-H), 3.61 (dd, J¼10.8, 1.4 Hz, 1-H, 6-H), 3.70
(dd, J¼9.7, 2.2 Hz, 1H, 10-H), 3.80 (dd, J¼11.0, 4.4 Hz, 1-H, 60-H), 3.83
(dd, J¼5.3, 2.4 Hz, 1H, 9-H), 3.96 (dd, J¼9.0, 2.4 Hz, 1H, H-8), 4.17 (d,
J¼11.5 Hz, 1H, CH2–Ph), 4.28 (d, J¼11.5 Hz, 1H, CH2–Ph), 4.32 (dd,
J¼8.4, 2.4 Hz, 1H, H-3), 4.33–4.38 (m, 2H, 13-H, 130-H), 4.36
(d, J¼11.5 Hz, 1H, CH2–Ph), 4.43 (d, J¼8.4 Hz, 1H, 1-H), 4.46
(d, J¼11.5 Hz, 1H, CH2–Ph), 4.52 (d, J¼12.1 Hz, 1H, CH2–Ph), 4.55 (d,
J¼12.1 Hz, 1H, CH2–Ph), 4.59 (d, J¼12.1 Hz, 1H, CH2–Ph), 4.66 (d,
J¼12.1 Hz, 1H, CH2–Ph), 4.71 (d, J¼11.5 Hz, 1H, CH2–Ph), 4.75
(d, J¼12.1 Hz, 1H, CH2–Ph), 4.87 (d, J¼11.5 Hz, 1H, CH2–Ph), 4.89 (d,
J¼11.5 Hz, 1H, CH2–Ph), 5.12 (d, J¼10.2 Hz, 1H, 7-H), 7.05–7.25 (m,
(neat):
n
¼3030, 2872, 1546, 1452, 1379, 1355, 1268, 1127, 1053, 939,
905, 733, 696, 634, 595 cmꢂ1. Anal. Calcd (%) for C21H25NO6
(387.43): C, 65.10; H, 6.50; N, 3.62. Found: C, 65.02; H, 6.72; N, 3.24.
4.4.9. Methyl 3,6,8,9,10,12-hexa-O-benzyl-2-deoxy-2-C-
nitromethyl-b-D-maltopyranoside (malto-20k)
Colorless oil (1.09 g, 58%); Rf¼0.50 (cyclohexane/ethyl acetate
20
2:1); [
a
]
þ41.2 (c 1.00, CHCl3); 1H NMR (500 MHz, CDCl3):
¼2.44
d
D
(dddd, J¼12.6, 9.9, 8.8, 5.2 Hz, 1H, 2-H), 3.48 (s, 3H, OMe), 3.51 (dd,
J¼10.1, 2.4 Hz, 1H, 12-H), 3.54 (ddd, J¼9.6, 5.3, 4.1 Hz, 1H, 5-H), 3.60
(dd, J¼10.7, 3.6 Hz,1H,120-H), 3.64 (dd, J¼10.7, 9.6 Hz,1H, 4-H), 3.75
(dd, J¼10.7, 8.8 Hz,1H, 9-H), 3.77 (ddd, J¼10.2, 3.6, 2.4 Hz,1H,11-H),
3.84 (dd, J¼10.2, 8.8 Hz, 1H, 10-H), 3.92 (dd, J¼10.7, 3.8 Hz, 1H, 8-H),
3.96 (dd, J¼11.4, 4.1 Hz, 1-H, 6-H), 4.10 (d, J¼8.2 Hz, 1H, 1-H), 4.36–
4.38 (m, 2H,13-H,130-H), 4.45 (dd, J¼11.2, 5.3 Hz,1H, 60-H), 4.47 (dd,
J¼10.7, 8.8 Hz, 1H, 3-H), 4.52 (d, J¼12.0 Hz, 1H, CH2–Ph), 4.52 (d,
J¼11.2 Hz, 1H, CH2–Ph), 4.53 (d, J¼12.0 Hz, 1H, CH2–Ph), 4.54
(d, J¼12.0 Hz, 1H, CH2–Ph), 4.55 (d, J¼12.0 Hz, 1H, CH2–Ph), 4.57 (d,
J¼11.2 Hz, 1H, CH2–Ph), 4.62 (d, J¼12.0 Hz, 1H, CH2–Ph), 4.78 (d,
J¼11.2 Hz, 1H, CH2–Ph), 4.80 (d, J¼11.2 Hz, 1H, CH2–Ph), 4.82
(d, J¼11.2 Hz, 1H, CH2–Ph), 4.87 (d, J¼11.2 Hz, 1H, CH2–Ph), 5.00 (d,
J¼11.2 Hz, 1H, CH2–Ph), 5.28 (d, J¼3.6 Hz, 1H, 7-H), 7.13–7.30 (m,
30H, arom. H); 13C NMR (75 MHz, CDCl3):
d
¼46.5 (d, C-2), 57.0 (q,
OMe), 67.9, 68.1 (2t, C-6, C-12), 72.3 (t, CH2–NO2), 72.7, 73.1 (2t,
CH2–Ph), 73.1 (d, C-3), 73.4 (t, CH2–Ph), 73.7 (d, C-4), 74.7, 74.9 (2t,
CH2–Ph), 75.3 (d, C-5), 75.3 (t, CH2–Ph), 77.2, 77.4, 80.0, 82.4, 101.4,
102.6 (6d, C-8, C-9, C-10, C-11, C-1, C-7), 127.3, 127.4, 127.5, 127.5,
127.6, 127.7, 127.8, 127.9, 128.0, 128.1, 128.2, 128.3, 128.4 (m, arom.
C–H), 138.1, 138.2, 138.4, 138.5, 138.7, 139.0 (6s, arom. C–CH2O); IR
(neat):
n
¼3028, 2862, 1555, 1495, 1452, 1361, 1207, 1046, 909, 731,
694, 600, 568, 555 cmꢂ1. Anal. Calcd (%) for C56H61NO12 (940.09): C,
71.55; H, 6.54; N, 1.49. Found: C, 71.32; H, 6.81; N, 1.60.
30H, arom. H); 13C NMR (75 MHz, CDCl3):
d
¼45.3 (d, C-2), 56.9 (q,
4.4.12. Methyl 3,6,8,9,10,12-hexa-O-benzyl-2-deoxy-2-epi-2-C-
nitromethyl-a-D-lactopyranoside (epi-lacto-20l)
OMe), 68.5, 69.2 (2t, C-6, C-12), 71.2 (d, C-3), 72.4 (t, CH2–NO2), 72.5,
73.3, 73.4, 73.5, 75.0 (5t, CH2–Ph), 75.5 (d, C-4), 75.5(t, CH2–Ph), 75.6,
77.8, 78.7, 79.7, 82.0, 97.4,101.4(7d, C-5, C-8, C-9, C-10, C-11, C-7, C-1),
127.5, 127.6, 127.7, 127.8, 127.9, 128.0, 128.3, 128.3, 128.4, 128.4 (m,
arom. C–H), 137.8, 137.8, 138.0, 138.3, 138.3, 138.6 (6s, arom. C–
Colorless oil (170 mg, 9%); Rf¼0.52 (cyclohexane/ethyl acetate
20
2:1); [
a
]
þ19.6 (c 0.99, CHCl3); 1H NMR (300 MHz, CDCl3):
¼3.03
d
D
(dddd, J¼9.5, 8.1, 5.9, 3.5 Hz, 1H, 2-H), 3.37 (s, 3H, OMe), 3.37 (ddd,
J¼4.6, 3.8, 2.8 Hz,1H, 5-H), 3.42 (dd, J¼4.6, 3.1 Hz,1H, 4-H), 3.48 (dd,
J¼10.8, 5.4 Hz,1H,12-H), 3.52 (ddd, J¼9.2, 5.9, 2.3 Hz,1H,11-H), 3.58
(dd, J¼10.8, 2.0 Hz,1H,120-H), 3.68 (dd, J¼9.2, 4.0 Hz,1H,10-H), 3.76
(dd, J¼8.7, 9.8 Hz, 1H, H-8), 3.82 (dd, J¼11.0, 3.8 Hz, 1-H, 6-H), 3.90
(dd, J¼11.0, 2.8 Hz,1H, 60-H), 4.02 (dd, J¼8.1, 3.1 Hz,1H, H-3), 4.26 (d,
J¼11.8 Hz, 1H, CH2–Ph), 4.30 (d, J¼11.5 Hz, 1H, CH2–Ph), 4.32 (d,
J¼8.1 Hz, 1H, 1-H), 4.33 (d, J¼11.8 Hz, 1H, CH2–Ph), 4.35 (dd, J¼8.7,
4.0 Hz, 1H, 9-H), 4.40 (d, J¼12.1 Hz, 1H, CH2–Ph), 4.54 (d, J¼11.5 Hz,
1H, CH2–Ph), 4.57 (d, J¼12.1 Hz, 1H, CH2–Ph), 4.58 (d, J¼11.5 Hz, 1H,
CH2–Ph), 4.62 (d, J¼11.5 Hz,1H, CH2–Ph), 4.65–4.73 (m, 2H,13-H,130-
H), 4.75 (d, J¼11.5 Hz, 1H, CH2–Ph), 4.81 (d, J¼11.5 Hz, 1H, CH2–Ph),
4.85 (d, J¼11.5 Hz,1H, CH2–Ph), 4.97 (d, J¼11.5 Hz, 1H, CH2–Ph), 5.16
(d, J¼10.7 Hz, 1H, 7-H), 7.21–7.36 (m, 30H, arom. H); 13C NMR
CH2O); IR (neat):
n
¼3031, 2873, 1540, 1487, 1402, 1394, 1209, 1087,
976, 738, 687, 632, 543, 521 cmꢂ1. Anal. Calcd (%) for C56H61NO12
(940.09): C, 71.55; H, 6.54; N, 1.49. Found: C, 71.67; H, 6.98; N, 1.62.
4.4.10. Methyl 3,6,8,9,10,12-hexa-O-benzyl-2-deoxy-2-epi-2-C-
nitromethyl-a-D-maltopyranoside (epi-malto-20k)
Colorless oil (225 mg, 12%); Rf¼0.55 (cyclohexane/ethyl acetate
20
2:1); [
a]
þ61.6 (c 0.99, CHCl3); 1H NMR (500 MHz, CDCl3):
¼2.80
d
D
(dddd, J¼10.5, 8.2, 5.8, 3.8 Hz,1H, 2-H), 3.31 (s, 3H, OMe), 3.50 (ddd,
J¼9.8, 6.4, 3.6 Hz, 1H, 5-H), 3.58 (dd, J¼10.7, 5.7 Hz, 1H, 12-H), 3.63
(dd, J¼9.4, 9.8 Hz, 1H, 4-H), 3.66 (dd, J¼10.8, 3.3 Hz, 1H, 120-H), 3.74
(ddd, J¼11.4, 5.7, 3.3 Hz, 1H, 11-H), 3.77 (dd, J¼10.1, 8.6 Hz, 1H, 9-H),
3.93 (dd, J¼9.3, 8.6 Hz, 1H, 10-H), 4.03 (dd, J¼10.1, 3.5 Hz, 1H, 8-H),
4. 11 (dd, J¼9.4, 3.4 Hz, 1H, 3-H), 4.31 (dd, J¼13.4, 3.8 Hz, 1H, 13-H),
4.34 (dd, J¼13.4, 3.8 Hz, 1H, 130-H), 4.38–4.39 (m, 2H, 6-H, 60-H),
4.41 (d, J¼8.2 Hz, 1H, 1-H), 4.46 (d, J¼11.5 Hz, 1H, CH2–Ph), 4.47 (d,
J¼11.5 Hz, 1H, CH2–Ph), 4.50 (d, J¼12.3 Hz, 1H, CH2–Ph), 4.52
(d, J¼11.5 Hz, 1H, CH2–Ph), 4.53 (d, J¼11.5 Hz, 1H, CH2–Ph), 4.56 (d,
J¼12.3 Hz, 1H, CH2–Ph), 4.59 (d, J¼12.3 Hz, 1H, CH2–Ph), 4.76 (d,
J¼11.5 Hz, 1H, CH2–Ph), 4.77 (d, J¼12.3 Hz, 1H, CH2–Ph), 4.82
(d, J¼11.5 Hz, 1H, CH2–Ph), 4.87 (d, J¼11.5 Hz, 1H, CH2–Ph), 5.00 (d,
J¼11.5 Hz, 1H, CH2–Ph), 5.30 (d, J¼3.5 Hz, 1H, 7-H), 7.14–7.32 (m,
(75 MHz, CDCl3):
d
¼42.4 (d, C-2), 57.2 (q, OMe), 68.4 (t, C-6), 68.7 (t,
C-12), 71.0 (d, C-3), 72.7 (t, CH2–NO2), 72.7, 72.9, 73.3, 73.5 (4t, CH2–
Ph), 73.5 (d, C-4), 73.8 (d, C-5), 74.5 (d, C-8), 74.6, 75.2 (2t, CH2–Ph),
75.4 (d, C-9), 80.0 (d, C-10), 82.4 (d, C-11), 98.9 (d, C-1),103.3 (d, C-7),
127.4, 127.6, 127.7, 127.8, 128.1, 128.2, 128.3 (m, arom. C–H), 138.1,
138.2, 138.4, 138.5, 138.8, 138.8 (6s, arom. C–CH2O); IR (neat):
n
¼3033, 2799, 1547, 1487, 1465, 1321, 1256, 1135, 967, 721, 687, 643,
554 cmꢂ1. Anal. Calcd (%) for C56H61NO12 (940.09): C, 71.55; H, 6.54;
N, 1.49. Found: C, 71.93; H, 6.59; N, 1.74.
30H, arom. H); 13C NMR (75 MHz, CDCl3):
d
¼43.7 (d, C-2), 55.2 (q,
4.5. General procedure for the catalytic hydrogenation of the
nitromethyl-pyranosides 20
OMe), 68.7, 69.0 (2t, C-6, C-12), 70.9, 71.2 (2d, C-3, C-4), 73.1 (t, CH2–
NO2), 73.2, 73.3, 73.3, 73.4, 75.0, 75.5 (6t, CH2–Ph), 76.1, 77.7, 77.8,
79.9, 81.9, 97.5, 97.7 (7d, C-5, C-8, C-9, C-10, C-11, C-1, C-7), 127.4,
127.5, 127.6, 127.6, 127.7, 127.8, 127.8, 128.0, 128.3, 128.3, 128.5 (m,
arom. C–H), 137.9, 138.0, 138.0, 138.3, 138.3, 138.6 (6s, arom. C–
The 2-deoxy-2-C-nitromethyl-pyranoside 20 (1.0 mmol) was
dissolved in methanol (5 mL) and palladium on carbon (10%)
(120 mg) was added. The reaction mixture was stirred in an auto-
clave under H2 atmosphere (40 bar) for 1 h and TLC showed com-
plete conversion. The mixture was filtered over Celite,
concentrated, and acetylated with acetic anhydride (0.5 mL) for
CH2O); IR (neat):
n
¼3030, 2862, 1571, 1462, 1441, 1372, 1237, 1075,
976, 731, 696, 654, 543 cmꢂ1. Anal. Calcd (%) for C56H61NO12
(940.09): C, 71.55; H, 6.54; N, 1.49. Found: C, 71.43; H, 6.86; N, 1.65.

E. Elamparuthi et al. / Tetrahedron 64 (2008) 11925–11937
11935
30 min. After concentration in vacuum, the crude product was
purified by column chromatography (ethyl acetate/methanol 8: 2),
affording the branched-chain glycosamines 21 in analytically pure
form.
Ac), 2.06 (dddd, J¼11.6, 8.6, 6.3, 4.3 Hz, 1H, 2-H), 2.80 (dd, J¼11.0,
8.5 Hz, 1H, 13-H), 3.28 (s, OMe), 3.34 (dd, J¼11.6, 6.3 Hz, 1H, 130-H),
3.42 (dd, J¼11.4, 4.4 Hz, 1H, 12-H), 3.48 (ddd, J¼9.3, 5.4, 3.3 Hz, 1H,
5-H), 3.53 (dd, J¼11.0, 2.9 Hz, 1H, 120-H), 3.70 (ddd, J¼10.7, 5.9,
2.4 Hz, 1H, 11-H), 3.76 (dd, J¼8.7, 7.0 Hz, 1H, 4-H), 3.78 (dd, J¼9.0,
6.4 Hz, 1H, 10-H), 3.83 (dd J¼9.3, 8.6 Hz, 1H, 3-H), 4.01 (dd, J¼12.0,
6.6 Hz, 1H, 6-H), 4.06 (dd, J¼9.3, 8.6 Hz, 1H, 9-H), 4.20 (dd, J¼12.0,
6.2 Hz, 1H, 60-H), 4.32 (dd, J¼8.6, 3.5 Hz, 1H, 8-H), 4.69 (s, 6H, OH),
4.70 (d, J¼8.6 Hz, 1H, 1-H), 4.83 (d, J¼3.5 Hz, 1H, 7-H); 13C NMR
4.5.1. Methyl 2-acetamidomethyl-2-deoxy-b-D-glucopyranoside
(gluco-21b)
Colorless syrup (200 mg, 82%); Rf¼0.50 (ethyl acetate/methanol
20
8:2); [
a
]
ꢂ8.1 (c 0.99, H2O); 1H NMR (300 MHz, D2O):
¼1.51
d
D
(dddd, J¼12.1, 10.6, 8.8, 5.6 Hz, 1H, 2-H), 1.91 (s, 3H, Ac), 3.18–3.26
(m, 1H, 5-H), 3.27 (dd, J¼8.8, 4.6 Hz, 1H, 4-H), 3.29 (dd, J¼10.9,
5.4 Hz, 1H, 6-H), 3.38 (dd, J¼8.8, 4.5 Hz,1H, 3-H), 3.43 (s, OMe), 3.47
(dd, J¼14.1, 3.1 Hz, 1H, 60-H), 3.62 (dd, J¼12.2, 5.6 Hz, 1H, 7-H), 3.82
(dd, J¼12.1, 1.5 Hz, 1H, 70-H), 4.29 (d, J¼8.8 Hz, 1H, 1-H), 4.69 (s, 3H,
(75 MHz, D2O):
d
¼20.6 (q, Ac), 36.8 (t, CH2–NH), 47.8 (d, C-2), 54.9
(q, OMe), 61.0, 61.2 (2t, C-6, C-12), 69.2, 69.8, 71.1, 72.3, 73.1, 73.4,
79.4 (7d, C-3, C-4, C-5, C-8, C-9, C-10, C-11), 97.1, 103.1 (2d, C-1, C-7),
171.6 (s, Ac); IR (neat):
n
¼3345, 2982, 1732, 1564, 1427, 1286, 1144,
1053, 981, 562 cmꢂ1; HRMS (ES) (C16H29NO11): calcd for [MþNa]:
OH); 13C NMR (75 MHz, D2O):
d¼22.3 (q, Ac), 36.4 (t, CH2–NH), 48.0
434.1638, found: 434.1642.
(d, C-2), 57.4 (q, OMe), 61.4 (t, C-6), 71.1, 72.5, 76.1 (3d, C-3, C-4, C-5),
103.2 (d, C-1), 174.6 (s, Ac); IR (neat):
n
¼3276, 2867, 1627, 1552,
4.5.6. Methyl 2-acetamidomethyl-2-deoxy-b-D-lactopyranoside
(lacto-21l)
1451, 1370, 1210, 1069, 1024, 733, 696, 604, 573 cmꢂ1; HRMS (ES)
(C10H19NO6): calcd for [MþNa]: 272.1110, found: 272.1128.
Colorless syrup (300 mg, 73%); Rf¼0.59 (ethyl acetate/methanol
20
7:3); [
a]
ꢂ5.4 (c 0.99, H2O); 1H NMR (300 MHz, D2O):
¼2.00 (s,
d
D
4.5.2. Methyl 2-acetamidomethyl-2-deoxy-
b
-D-galactopyranoside
3H, Ac), 2.35 (dddd, J¼11.0, 8.8, 6.8, 4.6 Hz,1H, 2-H), 3.28 (dd, J¼11.1,
6.8 Hz, 1H, 13-H), 3.36 (dd, J¼11.7, 2.0 Hz, 1H, 12-H), 3.43 (s, OMe),
3.46 (dd, J¼11.1, 3.4 Hz, 1H, 130-H), 3.52 (ddd, J¼8.8, 6.9, 3.5 Hz, 1H,
5-H), 3.58 (ddd, J¼10.1, 7.6, 3.7 Hz, 1H, 11-H), 3.60 (dd, J¼9.8, 3.2 Hz,
1H, 9-H), 3.65 (dd, J¼8.8, 3.4 Hz, 1H, 3-H), 3.70 (dd, J¼8.4, 3.4 Hz,
1H, 4-H), 3.75 (dd, J¼12.4, 5.1 Hz, 1H, 6-H), 3.82 (dd, J¼9.6, 3.2 Hz,
1H, 10-H), 3.91 (dd, J¼12.2, 2.0 Hz, 1H, 120-H), 4.38 (d, J¼7.7 Hz, 1H,
7-H), 4.49 (d, J¼8.8 Hz, 1H, 1-H), 4.62 (dd, J¼13.1, 6.2 Hz, 1H, 60-H),
4.69 (s, 6H, OH), 4.72 (dd, J¼9.8, 7.7 Hz, 1H, H-8); 13C NMR (75 MHz,
(galacto-21h)
Colorless syrup (193 mg, 77%); Rf¼0.44 (ethyl acetate/methanol
20
8:2); [
a
]
ꢂ4.9 (c 1.00, H2O); 1H NMR (300 MHz, D2O):
¼1.64–1.74
d
D
(m, 1H, 2-H), 1.90 (s, 3H, Ac), 3.24 (ddd, J¼12.6, 7.3, 1.7 Hz, 1H, 5-H),
3.43 (s, OMe), 3.44 (dd, J¼12.6, 4.7 Hz, 1H, 3-H), 3.47–3.55 (m, 2H,
6-H, 60-H), 3.64 (dd, J¼11.8, 4.7 Hz, 1H, 4-H), 3.71–3.74 (m, 2H, 7-H,
70-H), 4.21 (d, J¼8.9 Hz, 1H, 1-H), 4.69 (s, 3H, OH); 13C NMR
(75 MHz, D2O):
d¼22.3 (q, Ac), 36.4 (t, CH2–NH), 43.2 (d, C-2), 57.4
(q, OMe), 61.7 (t, C-6), 67.8, 69.7, 75.3 (3d, C-3, C-4, C-5), 103.7 (d, C-
D2O):
d
¼20.6 (q, Ac), 36.2 (t, CH2–NH), 47.9 (d, C-2), 57.5 (q, OMe),
1), 174.6 (s, Ac); IR (neat):
n
¼3304, 2936, 1735, 1633, 1556, 1371,
61.0, 61.4 (2t, C-6, C-12), 69.8, 72.1, 72.8, 73.1, 73.3, 74.8, 75.0 (7d, C-
3, C-4, C-5, C-8, C-9, C-10, C-11), 100.2, 103.1 (2d, C-1, C-7), 171.7 (s,
1234, 1032, 776, 588 cmꢂ1; HRMS (ES) (C10H19NO6): calcd for
[MþNa]: 272.1110, found: 272.1120.
Ac); IR (neat):
n
¼3334, 2930, 2493, 1724, 1562, 1372, 1241, 1028,
893, 779, 597 cmꢂ1; HRMS (ES) (C16H29NO11): calcd for [MþNa]:
4.5.3. Methyl 2-acetamidomethyl-2-deoxy-
b
-D-xylopyranoside
434.1638, found: 434.1662.
(xylo-21i)
Colorless syrup (170 mg, 78%); Rf¼0.60 (ethyl acetate/methanol
4.6. General procedure for the catalytic hydrogenation of the
isoxazoline N-oxides 19
20
8:2); [
a
]
ꢂ20.1 (c 1.00, H2O); 1H NMR (300 MHz, D2O):
d
¼1.44–
D
1.53 (m, 1H, 2-H), 1.90 (s, 3H, Ac), 3.15 (dd, J¼10.1, 11.6 Hz, 1H, 5-H),
3.23–3.35 (m, 2H, 6-H, 60-H), 3.39 (s, OMe), 3.44 (dd, J¼5.3, 9.2 Hz,
1H, 4-H), 3.51 (dd, J¼5.3, 8.8 Hz, 1H, 3-H), 3.86 (dd, J¼5.2, 11.6 Hz,
1H, 50-H), 4.25 (d, J¼8.6 Hz, 1H, H-1), 4.69 (s, 2H, OH); 13C NMR
The isoxazoline N-oxide 19 (1.0 mmol) was dissolved in meth-
anol (5 mL) and Raney nickel (50% in H2O, 600 mg) was added. The
reaction mixture was stirred in an autoclave under H2 atmosphere
(80 bar) for 1–2 days until TLC showed complete conversion. The
mixture was filtered over Celite, washed with methanol (10 mL),
concentrated, and acetylated with pyridine (5.0 mL) and acetic
anhydride (10 mL) for 1 day. After concentration in vacuum, the
diastereomeric ratios were determined by 1H NMR (500 MHz) on
the crude products. Purification by column chromatography (hex-
ane/ethyl acetate 1: 2) afforded the C-glycosylated amino acids 22
as an anomeric mixture in the yields depicted in Table 2. The 1,2-
diequatorially configured main products were isolated by MPLC
(medium pressure liquid chromatography) (hexane/ethyl acetate 1:
2) in analytically pure form.
(75 MHz, D2O):
d
¼22.3 (q, Ac), 36.4 (t, CH2–NH), 47.5 (d, C-2), 57.3
(q, OMe), 65.2 (t, C-5), 70.5, 72.2 (2d, C-3, C-4), 103.8 (d, C-1), 174.6
(s, Ac); IR (neat):
n
¼3296, 2913, 1626, 1552, 1437, 1297, 1214, 1155,
1043, 1001, 943, 639, 599 cmꢂ1; HRMS (ES) (C9H17NO5): calcd for
[MþNa]: 242.1004, found: 242.1016.
4.5.4. Methyl 2-acetamidomethyl-2-deoxy-a-D-arabinopyranoside
(arabino-21j)
Colorless syrup (165 mg, 75%); Rf¼0.53 (ethyl acetate/methanol
20
8:2); [
a
]
D
ꢂ4.2 (c 1.00, H2O); 1H NMR (300 MHz, D2O):
¼1.00–
d
1.08 (m, 1H, 2-H), 1.90 (s, 3H, Ac), 3.17 (s, OMe), 3.30 (dd, J¼10.2,
6.6 Hz, 1H, 3-H), 3.38–3.51 (m, 2H, 6-H, 60-H), 3.54 (dd, J¼10.2, 6.9,
1.1 Hz, 1H, 4-H), 3.62 (dd, J¼12.2, 3.4 Hz, 1H, 5-H), 3.80 (dd, J¼12.8,
3.1 Hz, 1H, 50-H), 4.17 (d, J¼8.2 Hz, 1H, 1-H), 4.69 (s, 2H, OH); 13C
4.6.1. gluco-Amino acid (S-22a)
20
Colorless oil; Rf¼0.35 (hexane/ethyl acetate 1:2); [
a]
þ72.6 (c
D
NMR (75 MHz, D2O):
d¼22.3 (q, Ac), 36.6 (t, CH2–NH), 43.6 (d, C-2),
1.00, CHCl3); 1H NMR (300 MHz, CDCl3):
d
¼1.34 (t, J¼7.2 Hz, 3H,
57.2 (q, OMe), 66.0 (t, C-5), 67.2, 69.1 (2d, C-3, C-4), 103.6 (d, C-1),
OCH2CH3), 1.96, 2.01, 2.05, 2.07 (4s, 3H each, 4OAc), 2.21 (s, 3H,
NHAc), 2.71 (ddd, J¼11.4, 9.2, 1.4 Hz, 1H, 2-H), 3.73 (ddd, J¼10.0, 4.4,
2.1 Hz, 1H, 5-H), 4.06 (dd, J¼12.5, 2.1 Hz, 1H, 6-H), 4.26 (q, J¼7.2 Hz,
2H, OCH2CH3), 4.29 (dd, J¼12.5, 4.4 Hz, 1H, 60-H), 4.98 (dd, J¼8.8,
1.4 Hz, 1H, 7-H), 5.05 (dd, J¼10.0, 9.2 Hz, 1H, 4-H), 5.21 (dd, J¼11.4,
9.2 Hz, 1H, 3-H), 5.39 (d, J¼9.2 Hz, 1H, 1-H), 6.19 (d, J¼8.8 Hz, 1H,
174.8 (s, Ac); IR (neat):
n
¼3324, 2943, 1654, 1492, 1417, 1287, 1153,
1049, 967, 587 cmꢂ1; HRMS (ES) (C9H17NO5): calcd for [MþNa]:
242.1004, found: 242.1002.
4.5.5. Methyl 2-acetamidomethyl-2-deoxy-b-D-maltopyranoside
(malto-21k)
NHAc); 13C NMR (75 MHz, CDCl3):
d
¼14.2 (q, OCH2CH3), 20.4, 20.5,
Colorless syrup (290 mg, 71%); Rf¼0.54 (ethyl acetate/methanol
20.7, 20.8 (4q, 4OAc), 23.1 (q, NHAc), 47.4, 48.0 (2d, C-2, C-7), 61.7 (t,
20
7:3); [
a]
ꢂ12.8 (c 1.01, H2O); 1H NMR (300 MHz, D2O):
d
¼1.97 (s,
OCH2CH3), 62.7 (d, C-6), 68.8, 69.9, 72.4 (3d, C-3, C-4, C-5), 91.7 (d,
D

11936
E. Elamparuthi et al. / Tetrahedron 64 (2008) 11925–11937
C-1), 168.7 (s, CO2Et), 169.6, 170.5, 170.6, 170.8, 170.9 (5s, 4OAc,
5.32 (dd, J¼10.6, 9.4 Hz, 1H, 30-H), 5.38 (d, J¼9.2 Hz, 1H, 1-H), 6.36
NHAc); IR (neat):
n
¼3417, 2963, 1749, 1688, 1525, 1443, 1373, 1261,
(d, J¼9.6 Hz, 1H, NHAc); 13C NMR (75 MHz, CDCl3):
d¼14.1 (q,
1026, 801 cmꢂ1. Anal. Calcd (%) for C20H29NO12 (475.44): C, 50.53;
H, 6.15; N, 2.95. Found: C, 49.98; H, 6.48; N, 2.88.
CO2CH2CH3), 20.3, 20.4, 20.5, 20.6, 20.7, 20.8, 20.9, 23.1 (8q, 7OAc,
NHAc), 474, 47.6 (2d, C-2, C-7), 61.4, 61.9, 62.8 (3t, C-6, C-60,
CO2CH2CH3), 67.9, 68.6, 69.2, 69.9, 72.2, 73.0, 73.9 (7d, C-3, C-4, C-5,
C-20, C-30, C-40, C-50), 91.3, 95.8 (2d, C-1, C-10), 168.5, 169.3, 169.7,
170.2, 170.3, 170.4, 170.5, 170.7, 171.5 (9s, 7OAc, NHAc, CO2Et); IR
4.6.2. galacto-Amino acid (S-22c)
20
Colorless oil; Rf¼0.52 (hexane/ethyl acetate 1:5); [
a]
ꢂ53.2 (c
D
1.04, CHCl3); 1H NMR (300 MHz, CDCl3):
d
¼1.32 (t, J¼7.1 Hz, 3H,
(neat):
n
¼3404, 2962, 1748, 1688, 1518, 1435, 1371, 1334, 1225, 1168,
OCH2CH3), 2.02, 2.03, 2.10, 2.10 (4s, 3H each, 3OAc, 1NHAc), 2.90
(ddd, J¼12.0, 9.4, 1.6 Hz, 1H, 2-H), 3.93 (ddd, J¼6.8, 6.3, 0.8 Hz, 1H,
5-H), 4.05 (dd, J¼11.3, 6.3 Hz, 1H, 6-H), 4.12–4.19 (m, 1H,
CO2CH2CH3), 4.13 (dd, J¼11.3, 6.8 Hz, 1H, 60-H), 4.20–4.28 (m 1H, 4-
H), 4.25 (dq, J¼10.8, 7.1 Hz, 1H, CO2CH2CH3), 4.97 (dd, J¼8.5, 1.6 Hz,
1H, 7-H), 5.06 (dd, J¼12.0, 3.2 Hz, 1H, 3-H), 5.39 (d, J¼9.4 Hz, 1H, 1-
1138, 1038, 939, 894 cmꢂ1. Anal. Calcd (%) for C32H45NO20 (763.70):
C, 50.33; H, 5.94; N, 1.83. Found: C, 50.62; H, 6.11; N, 2.02.
4.6.6. lacto-Amino acid (S-22g)
20
Colorless oil; Rf¼0.34 (hexane/ethyl acetate 1:5); [
a
]
þ46.4 (c
D
1.00, CHCl3); 1H NMR (500 MHz, CDCl3):
d
¼1.33 (t, J¼7.1 Hz,
H), 6.24 (d, J¼8.5 Hz, 1H, NHAc); 13C NMR (75 MHz, CDCl3):
d
¼14.1
CO2CH2CH3), 1.96, 2.00, 2.04, 2.05, 2.06, 2.11, 2.15, 2.19 (8s, 3H each,
7OAc, NHAc), 2.64 (ddd, J¼11.5, 9.3,1.2 Hz,1H, 2-H), 3.62 (ddd, J¼9.8,
4.8,1.8 Hz, 1H, 5-H), 3.72 (dd, J¼9.7, 8.9 Hz, 1H, 4-H), 3.85 (dd, J¼7.5,
6.0 Hz,1H, 50-H), 4.03 (dd, J¼11.0, 7.5 Hz,1H, 60a-H), 4.14 (dd, J¼12.0,
4.0 Hz, 1H, 6a-H), 4.17–4.21 (m, 1H, 60b-H), 4.21 (q, J¼7.1 Hz, 2H,
CO2CH2CH3), 4.40 (d, J¼7.8 Hz,1H, 10-H), 4.41 (dd, J¼12.0,1.8 Hz,1H,
6b-H), 4.93 (dd, J¼10.4, 3.5 Hz, 1H, 30-H), 5.01 (dd, J¼9.2, 1.2 Hz,
1H, 7-H), 5.07 (dd, J¼10.4, 7.8 Hz, 1H, 20-H), 5.13 (dd, J¼11.5, 8.9 Hz,
1H, 3-H), 5.33 (d, J¼9.3 Hz,1H,1-H), 5.35 (d, J¼3.2 Hz,1H, 40-H), 6.32
(q, OCH2CH3), 20.3, 20.4, 20.5, 20.7 (4q, 4OAc), 23.0 (q, NHAc), 42.9,
47.9 (2d, C-2, C-7), 61.2 (t, OCH2CH3), 61.8 (d, C-6), 65.9, 68.3, 71.2
(3d, C-3, C-4, C-5), 91.9 (d, C-1), 168.7, 170.0, 170.1, 170.3, 170.7, 171.1
(6s, 4OAc, CO2Et, NHAc); IR (neat):
n
¼3415, 2961, 1738, 1692, 1523,
1443, 1365, 1268, 1029, 805 cmꢂ1. Anal. Calcd (%) for C20H29NO12
(475.44): C, 50.53; H, 6.15; N, 2.95. Found: C, 49.88; H, 6.23; N, 2.83.
4.6.3. xylo-Amino acid (S-22d)
20
Colorless oil; Rf¼0.62 (hexane/ethyl acetate 1:5); [
a
]
þ6.5 (c
(d, J¼9.2 Hz, 1H, NHAc); 13C NMR (75 MHz, CDCl3):
d
¼14.2 (q,
D
0.96, CHCl3); 1H NMR (300 MHz, CDCl3):
d
¼1.32 (t, J¼7.1 Hz, 3H,
CO2CH2CH3), 20.3, 20.4, 20.5, 20.6, 20.7, 20.8, 20.9, 23.2 (8q, 7OAc,
NHAc), 47.4, 48.0 (2d, C-2, C-7), 60.9, 64.4, 64.6 (3t, C-6, C-60,
CO2CH2CH3), 66.6, 68.9, 69.7, 70.7, 70.8, 70.9, 73.4, 78.4 (7d, C-3, C-4,
C-5, C-20, C-30, C-40, C-50), 91.6, 101.0 (2d, C-1, C-10), 168.7, 169.0,
170.0, 170.1, 170.2, 170.3, 170.5, 170.8, 170.9 (9s, 7OAc, NHAc, CO2Et);
CO2CH2CH3), 1.98, 2.01, 2.05 (3s, 3H each, OAc), 2.19 (s, 3H, NHAc),
2.65 (ddd, J¼11.5, 9.0, 1.7 Hz, 1H, 2-H), 3.38 (dd, J¼11.8, 9.7 Hz, 1H,
5-H), 4.08 (dd, J¼11.8, 5.5 Hz, 1H, 50-H), 4.11 (q, J¼7.1 Hz, 2H,
CO2CH2CH3), 4.92–5.01 (m, 1H, 4-H), 4.98 (dd, J¼8.8, 1.7 Hz, 1H, 6-
H), 5.18 (dd, J¼11.5, 9.1 Hz, 1H, 3-H), 5.35 (d, J¼9.0 Hz, 1H, 1-H), 6.25
IR (neat):
n
¼3404, 2941,1751,1687,1518,1435,1371,1221,1169,1137,
(d, J¼8.8 Hz, 1H, NHAc); 13C NMR (75 MHz, CDCl3):
d
¼14.1 (q,
1067, 953, 898 cmꢂ1. Anal. Calcd (%) for C32H45NO20 (763.70): C,
50.33; H, 5.94; N, 1.83. Found: C, 50.02; H, 6.01; N, 1.86.
CO2CH2CH3), 20.5, 20.6, 20.7 (3q, 3OAc), 23.1 (q, NHAc), 46.9 (d, C-
2), 48.1 (d, C-6), 62.0 (t, CO2CH2CH3), 63.4 (t, C-5), 69.4, 69.8 (2d, C-
3, C-4), 92.3 (d, C-1), 168.9 (s, CO2Et), 169.9, 170.5, 170.9, 171.0 (4s,
Acknowledgements
NHAc, 3OAc); IR (neat):
n
¼3342, 2948, 1749, 1685, 1543, 1438, 1372,
1215, 1013, 937 cmꢂ1. Anal. Calcd (%) for C17H25NO10 (403.38): C,
50.62; H, 6.25; N, 3.47. Found: C, 50.45; H, 6.12; N, 3.27.
This work was generously supported by the Deutsche For-
schungsgemeinschaft (Li 556/7-3).
4.6.4. arabino-Amino acid (R-22e)
Supplementary data
20
Colorless oil; Rf¼0.67 (hexane/ethyl acetate 1:5); [
a
]
þ55.7 (c
D
1.01, CHCl3); 1H NMR (300 MHz, CDCl3):
d
¼1.28 (t, J¼7.1 Hz, 3H,
Complete characterization of all nucleophilic trapping products
16 is provided. Supplementary data associated with this article can
be found in the online version, at doi:10.1016/j.tet.2008.08.109.
CO2CH2CH3), 1.95, 2.04, 2.12, 2.20 (4s, 3H each, 3OAc, NHAc), 2.95
(ddd, J¼11.7, 9.3, 1.6 Hz, 1H, 2-H), 3.72 (dd, J¼13.4, 0.9 Hz, 1H, 5-H),
4.00 (dd, J¼13.5, 1.8 Hz, 1H, 50-H), 4.17 (dq, J¼10.8, 7.1 Hz, 1H,
CO2CH2H3), 4.27 (dq, J¼10.8, 7.1 Hz, 1H, CO2CH2H3), 5.00 (dd, J¼8.5,
1.6 Hz, 1H, 6-H), 5.09 (dd, J¼11.7, 3.3 Hz, 1H, 3-H), 5.13–5.16 (m, 1H,
4-H), 5.32 (d, J¼9.2 Hz, 1H, 1-H), 6.14 (d, J¼8.5 Hz, 1H, NHAc); 13C
References and notes
1. Books: (a) Giese, B. Radicals in Organic Synthesis: Formation of Carbon–Carbon
Bonds; Pergamon: Oxford, 1986; (b) Fossey, J.; Lefort, D.; Sorba, J. Free Radicals in
Organic Chemistry; Wiley: Chichester, UK, 1995; (c) Curran, D. P.; Porter, N. A.;
Giese, B. Stereochemistry of Radical Reactions; VCH: Weinheim, 1996; (d) Linker,
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VCH: Weinheim, 1998; (e) Radicals in Organic Synthesis; Renaud, P., Sibi, M. P.,
Eds.; Wiley-VCH: Weinheim, 2001; (f) Zard, S. Z. Radical Reactions in Organic
Synthesis; Oxford University Press: New York, NY, 2003; (g) Gansa¨uer, A. Rad-
icals in Synthesis, Topics in Current Chemistry; 2006; Vol. 263, pp 1–190; (h)
Gansa¨uer, A. Radicals in Synthesis, Topics in Current Chemistry; 2006; Vol. 264,
pp 1–236.
NMR (75 MHz, CDCl3):
(4q, 3OAc, NHAc), 43.4 (d, C-2), 48.1 (d, C-6), 61.7 (t, CO2CH2CH3),
d
¼14.2 (q, CO2CH2CH3), 20.5, 20.7, 20.8, 23.1
65.1 (t, C-5), 67.0, 67.9 (2d, C-3, C-4), 92.4 (d, C-1), 168.9, 170.2,
170.3, 170.4, 170.6 (5s, CO2Et, 3OAc, NHAc); IR (neat):
n
¼3407, 2926,
1745, 1663, 1542, 1442, 1374, 1235, 1034, 974 cmꢂ1. Anal. Calcd (%)
for C17H25NO10 (403.38): C, 50.62; H, 6.25; N, 3.47. Found: C, 51.03;
H, 5.98; N, 3.04.
2. Selected recent reviews: (a) Zard, S. Z. Org. Biomol. Chem. 2007, 5, 205–213; (b)
Schiesser, C. H.; Wille, U.; Matsubara, H.; Ryu, I. Acc. Chem. Res. 2007, 40, 303–
313; (c) Crich, D.; Grant, D.; Krishnamurthy, V.; Patel, M. Acc. Chem. Res. 2007,
40, 453–463; (d) Kim, S.; Kim, S. Bull. Chem. Soc. Jpn. 2007, 80, 809–822; (e)
Miyabe, H.; Takemoto, Y. Chem.dEur. J. 2007, 13, 7280–7286; (f) Oshima, K. Bull.
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Ed. 2007, 46, 7356–7359.
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4.6.5. malto-Amino acid (S-22f)
20
Colorless oil; Rf¼0.32 (hexane/ethyl acetate 1:5); [
a
]
þ142.2 (c
D
1.03, CHCl3); 1H NMR (300 MHz, CDCl3):
d
¼1.46 (t, 3H, J¼7.1 Hz,
CO2CH2CH3), 1.97, 2.01, 2.02, 2.04, 2.07, 2.09, 2.11, 2.12 (8q, 3H each,
7OAc, NHAc), 2.65 (ddd, J¼11.4, 9.2, 1.5 Hz, 1H, 2-H), 3.73 (ddd,
J¼9.3, 4.1, 2.5 Hz, 1H, 5-H), 3.91 (ddd, J¼10.4, 2.5, 2.2 Hz, 1H, 50-H),
3.93 (dd, J¼9.3, 8.8 Hz, 1H, 4-H), 4.06 (dd, J¼12.2, 2.2 Hz, 1H, 60a-H),
4.10–4.22 (m, 3H, 6a-H, CO2CH2CH3), 4.24 (dd, J¼11.9, 4.1 Hz, 1H, 6b-
H), 4.43 (dd, J¼12.2, 2.5 Hz, 1H, 60b-H), 4.90 (dd, J¼10.6, 3.8 Hz, 1H,
20-H), 5.04 (dd, J¼10.4, 9.4 Hz, 1H, 40-H), 5.05 (dd, J¼9.6, 1.5 Hz, 1H,
7-H), 5.26 (d, J¼3.8 Hz, 1H, 10-H), 5.27 (dd, J¼11.4, 8.8 Hz, 1H, 3-H),

E. Elamparuthi et al. / Tetrahedron 64 (2008) 11925–11937
11937
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