Preparation of enantiomerically pure 4-alkyl-5-formyl-4-nitrocyclohex-1-enes from 5-glyco-4-nitrocyclohex-1-enes

Article abstract of DOI:10.1016/S0957-4166(02)00416-0

Base-catalyzed (TMG, DBU or TEA) asymmetric Michael reactions between 5-glyco-4-nitrocyclohex-1-enes 1a or 1b and a number of mono- or α,β-disubstituted electron-deficient alkenes yielded, in all cases, adducts in which the sugar side-chain and the added group on C-4 of the cyclohexene ring showed a trans-relationship. Furthermore, some of the adducts have been used to prepare enantiomerically pure 4-alkyl-5-formyl-4-nitrocyclohex-1-enes by a two-step process involving base-catalyzed (NaOMe) deacetylation of their respective sugar side-chains and subsequent oxidative cleavage (NaIO₄). When reactions of 1a or 1b with dimethyl maleate, dimethyl fumarate or methyl trans-4-oxopentenoate were carried out with DBU (instead of TMG) as catalyst, there was in situ elimination of nitrous acid.

Full text of DOI:10.1016/S0957-4166(02)00416-0

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 1773–1787
Preparation of enantiomerically pure
4-alkyl-5-formyl-4-nitrocyclohex-1-enes from
5-glyco-4-nitrocyclohex-1-enes
R. Ballini,a G. Bosica,a M. V. Gil,b E. Roma´nb,* and J. A. Serranob
aDipartimento di Scienze Chimiche, Universita` di Camerino, v´ıa S. Agostino, 1, I-62032 Camerino, Italy
bDepartamento de Qu´ımica Orga´nica, Facultad de Ciencias, Universidad de Extremadura, 06071 Badajoz, Spain
Received 4 July 2002; accepted 22 July 2002
Abstract—Base-catalyzed (TMG, DBU or TEA) asymmetric Michael reactions between 5-glyco-4-nitrocyclohex-1-enes 1a or 1b
and a number of mono- or a,b-disubstituted electron-deficient alkenes yielded, in all cases, adducts in which the sugar side-chain
and the added group on C-4 of the cyclohexene ring showed a trans-relationship. Furthermore, some of the adducts have been
used to prepare enantiomerically pure 4-alkyl-5-formyl-4-nitrocyclohex-1-enes by a two-step process involving base-catalyzed
(NaOMe) deacetylation of their respective sugar side-chains and subsequent oxidative cleavage (NaIO4). When reactions of 1a or
1b with dimethyl maleate, dimethyl fumarate or methyl trans-4-oxopentenoate were carried out with DBU (instead of TMG) as
catalyst, there was in situ elimination of nitrous acid. © 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
In a preliminary communication,10 we reported briefly
on stereoselective Michael reactions between 5-glyco-4-
nitrocyclohexenes 1a or 1b and several electron-
deficient alkenes. The purpose of this paper is to
present in full details of those reactions, as well as to
extend the methodology to a range of other disubsti-
tuted symmetrical or non-symmetrical alkenes. More-
over, some of the adducts prepared have been used for
the enantioselective synthesis of 4-alkyl-5-formyl-4-
nitrocyclohex-1-enes.
Stereoselective carbonꢀcarbon bond-forming processes
with introduction of versatile functionalities are of
great interest for the preparation of target molecules
containing numerous stereogenic centres and branched
skeletons. Among the reactions that fit these require-
ments, the Michael addition with chiral nitro aliphatic
compounds as donors or acceptors plays a crucial role,
primarily due to the remarkable versatility of nitro
derivatives in their conversion into a variety of organic
functional groups.1 As examples of valuable enan-
tiomerically pure products that have been prepared
through this methodology, there are C-disaccharides,2
glycosylspirolactones,3 sugar-derived 1,3-dinitro com-
pounds,4 carbocyclic nucleosides,5 or some intermedi-
ates in one of the synthetic routes to the carbazole
alkaloids, staurosporine and staurosporinone,6 as well
as potential anxiolytic agents.7 In connection with the
present work, the Michael addition between 4-nitrocy-
clohexenes and a,b-unsaturated aldehydes is a key step
in the synthesis of several sesquiterpenes.8 Also, asym-
metric Michael reactions with nitro compounds using
chiral catalysts have been described in recent years.9
2. Results and discussion
Base-catalyzed asymmetric Michael reactions between
5-glyco-4-nitrocyclohex-1-enes 1a or 1b and a number
of mono- and a,b-disubstituted electron-deficient
alkenes11 yielded Michael adducts 2–11,a,b, in which
the sugar side-chain and the added group on C-4 of the
cyclohexene ring showed a trans-relationship (Scheme
1). The starting 1,2-dimethyl-(4S,5S)-5-(
-(4R,5R)-5-( -manno)-4-nitrocyclohexenes 1a and 1b
have been prepared by thermal asymmetric Diels–Alder
cycloaddition between sugar-derived -galacto- or D-
D-galacto)- and
D
D
manno-1-nitroalkenes and 2,3-dimethylbuta-1,3-diene
as described previously;12 also, cis-hex-3-en-2,6-dione
was synthesized as reported by Dom´ınguez et al.13
* Corresponding author. Tel.: +34-924289381; fax: +34-924271149;
e-mail: roman@unex.es
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00416-0

1774
R. Ballini et al. / Tetrahedron: Asymmetry 13 (2002) 1773–1787
R3
R3
R2
R3
NO2
R2
NO2
R1
R2
or
or
MeCN / base
R1
R1
12a, 13a
1a
1b
2a-11a
R3
R2
NO2
R1
R3
R2
NO2
R1
R3
R2
MeCN / base
R1
12b, 13b
2b-11b
2a, 2b; R2 = H, R3 = COOCH3
3a, 3b; R2 = H, R3 = COCH3
4a, 4b; R2 = H, R3 = CN
a; R1 = D-galacto-(CHOAc)4-CH2OAc
b; R1 = D-manno-(CHOAc)4-CH2OAc
5a, 5b; R2 = H, R3 = CHO
6a, 7a, 6b, 7b, 12a, 13a; R2 = R3 = COOCH3
8a, 9a, 8b, 9b, 12b, 13b; R2 = COOCH3, R3 = COCH3
10a, 11a, 10b, 11b; R2 = R3 = COCH3
Scheme 1.
compounds (series b) support a deviation of the planar-
ity for C-1%, in such a way that these sugar side-chains
The Michael additions (Scheme 1) were completed in
acetonitrile solvent at room temperature, using in most
cases a slight excess (1.1 equiv.) of the alkene acceptor
and basic catalyst [1,1,3,3-tetramethyl-guanidine
(TMG), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or
triethylamine (TEA)]. After reaction times of between
12 and 24 h, the 1H NMR spectra of the crude mixtures
showed complete disappearance of the starting material
and the formation of only one of the possible C-4
stereoisomers; i.e. 1a and 1b led exclusively to products
of the series a and b, respectively.
could be in the G− and G+ conformations, the latter
1
being more probable17 be1cause they would not present
1,3-parallel interactions between acetate groups on C-1%
and C-3%. On the other hand, crystallographic studies18
have supported the possibility that the terminal oxygen
atom of an acyclic sugar derivative may readily adopt a
gauche- or anti-periplanar disposition with respect to
the substituent located on C-4% (Fig. 1).
Concerning the connection between the sugar side-
chain and the cyclohexene ring, the couplings J1%,5 (8.7–
10.9 Hz) indicate that, in all cases, protons H-1% and
H-5 show an anti-periplanar relationship. As can be
deduced from the Karplus equation,19 the values of J5,6a
(4.1–5.9 Hz) and J5,6b (0–1.0 Hz) correspond to dihedral
angles H-5ꢀC-5ꢀC-6ꢀH-6a and H-5ꢀC-5ꢀC-6ꢀH-6b of
ca. 40 and 80°, respectively, thus evidencing that the
conformation of the cyclohexene ring corresponds to a
distorted half-chair,20 where the first carbon atoms of
both side-chains (C-1% and C-1¦) adopt arrangements
closer to axial than equatorial (Fig. 2).
The structures of the new adducts are supported by
elemental analysis, spectral data (IR, 1H and 13C NMR,
HRMS), and the X-ray single crystallographic analysis
of 2a. Thus, compounds 2–11,a,b clearly showed car-
bonyl acetate IR bands (1740 5 cm−1), as well as the
characteristic symmetric and antisymmetric stretching
of the N−O bonds (1365 5 and 1540 5 cm−1), the latter
being characteristic of tertiary alkyl nitro compounds.14
The ketonic carbonyl group in adducts from
methylvinylketone (3a,b), methyl trans-4-oxo-pen-
tenoate (8 and 9,a,b, 12b, 13b) and cis-hex-3-en-2,5-
dione (10 and 11a,b) was observed near 1710 cm−1. In
the case of adducts from acrolein (5a,b), the presence of
a band at ca. 2720 cm−1 is indicative of the formyl
group, whereas those from acrylonitrile (4a,b) presented
a weak CꢁN absorption at ca. 2240 cm−1.
Besides those signals corresponding to alkyl side-chains,
13C NMR spectra of compounds 2–11 showed similar
characteristics within each one of the series a or b.
Linkage of the alkene acceptor at C-4 (88.0–90.3 ppm)
was confirmed because in DEPT experiments no signal
for this carbon was evident, in contrast to what was
observed in the precursors 1a and 1b.
1
In the H NMR spectra (ca. 50 mg/mL, CDCl3 solu-
tions, room temperature), the magnitude of the
observed vicinal coupling constants between protons in
the sugar side-chains of the adducts indicate that the
preferred conformations for this fragment (C-1%ꢀC-5%)
From the X-ray data for 2a (Fig. 3 and Tables 1–3), the
deviation of the bond angle C-4ꢀC-5ꢀC-1% (118.6°) with
respect to the angle expected for a sp3-hybridized car-
bon is noteworthy. The enlargement of this angle is
probably a way to alleviate steric compression between
the nitro group and the acetate at C-1%. The torsion
in -galacto compounds (series a) are the zig-zag planar
D
(P conformations15), in agreement with those observed
for aldohexoses with the same configuration.16 How-
ever, the values of J1%,2% (3.7–4.0 Hz) in the
D-manno

R. Ballini et al. / Tetrahedron: Asymmetry 13 (2002) 1773–1787
1775
Figure 1. Sugar side-chain conformations for Michael adducts 2–11 (series a and b).
angles from crystalline 2a were very similar to those
obtained in deuteriochloroform solution. Both alkyl
and sugar side-chains on C-4 and C-5 showed confor-
mations close to zig-zag planar, their first carbon atoms
C-1% and C-1¦ being in a practically trans-diaxial
arrangement (dihedral angle C-1¦–C-4–C-5–C-1%,
173.3°). On the other hand, the nitro group presents a
clear equatorial orientation, in such a way that the
nitrogen and the two oxygen atoms appear located
almost in the same average plane that is defined by the
cyclic fragment. As could be expected for a cyclohexene
ring,20 the olefinic carbons and the adjacent allylic
carbons are in the same plane, the other (C-4 and C-5)
being below and above of this plane, respectively. Table
Figure 2. Cyclohexene ring conformations for compounds
2–11.
,
3 shows the deviations (A) of the six carbons of the ring
in 2a with respect to the average plane of C-3, C-2, C-1
and C-6.
As we will discuss later, the stereochemistry of the
substituents at C-4 and C-5 is consistent with the
proposed mechanism for the Michael addition, which is
assumed to be the same for all of the adducts (2–11,a,b)
obtained; furthermore, the close similarity between
their NMR spectra within each series also supports the
configurations assigned to C-4. Thus, we found that for
the adducts in series a, the H-5 protons appear 0.31–
0.21 ppm upfield when they are compared with the
same protons in adducts of series b. The opposite
configurations at C-4 for the adducts in both series
were supported by the opposite values of the specific
rotations, that showed enantiomeric nitroaldehydes 2e
and 2f, prepared from 2a and 2b, respectively (see
Scheme 5), through reactions in which the configura-
tion at stereogenic centers did not change.
Figure 3. View of the crystal structure of 2a (A) and its
cyclohexene fragment (B). For clarity, hydrogen atoms in Fig.
3(A) have been omitted.
Table 1. Bond angles (°) in compound 2a
C-2ꢀC-1ꢀC-6
C-3ꢀC-2ꢀC-1
C-2ꢀC-3ꢀC-4
C-3ꢀC-4ꢀC-5
C-4ꢀC-5ꢀC-6
C-3ꢀC-4ꢀC-1¦
121.8
123.9
112.3
112.5
108.6
112.2
NꢀC-4ꢀC-1¦
NꢀC-4ꢀC-5
C-4ꢀC-5ꢀC-1%
C-1%ꢀC-5ꢀC-6
C-5ꢀC-6ꢀC-1
104.3
108.0
118.6
107.1
113.2
As shown in Scheme 2 for 1a, the stereochemical out-
come in these Michael additions could be justified by
supposing the electrophilic carbon of the electron-
deficient alkene adds to the less hindered face of the
intermediate carbanion 14a; that is to say, opposite to
where the bulky sugar side-chain is linked.

1776
R. Ballini et al. / Tetrahedron: Asymmetry 13 (2002) 1773–1787
Table 2. Dihedral angles (°) in compound 2a
all cases, ca. 1:1 diastereomeric mixtures in which the
adducts 6–11, a,b differ only in the stereochemistry at
the new C-1¦ stereogenic center. Assignment of the
1¦(R) or 1¦(S) configuration to these compounds is
based on NOE observations on 6a,b and 7a,b as well as
on correlation of NMR data; thus, the space proximity
between protons H-2¦a and H-5 in 6a and 7b [1¦(R)
and 1¦(S) configuration, respectively] was supported by
NOE effects (4.1–3.5%); however, no NOE effect was
observed between these same protons in 7a and 6b
[1¦(S) configuration and 1¦(R) configuration, respec-
tively]; instead, a 5.8%–4.3% NOE was observed
between H-2¦b and H-3a in these latter compounds.
For the adducts 8–11, a,b, configurations at C-1¦ have
been tentatively assigned by comparison of their 1H and
13C NMR spectra; for example, we found that for 1¦(R)
compounds of series a (6a, 8a, 10a), and for 1¦(S)
compounds of series b (7b, 9b, 11b), the resonances of
C-4 carbons appear in the range 90.0–90.5 ppm. On the
other hand, signals of C-4 were at 88.0–88.4 ppm in
1¦(S) compounds of series a (7a, 9a, 11a) and 1¦(R)
compounds of series b (6b, 8b, 10b). Fig. 4 shows
NꢀC-4ꢀC-5ꢀH-5
NꢀC-4ꢀC-5ꢀC-5
−60.9 NꢀC-4ꢀC-5ꢀC-1%
−176.9 NꢀC-4ꢀC-3ꢀH-3a
−42.1 NꢀC-4ꢀC-3ꢀC-2
60.7
75.2
−163.2
173.3
−40.8
11.8
76.3
−58.2
−176.8
57.6
NꢀC-4ꢀC-3ꢀH-3b
C-1¦ꢀC-4ꢀC-5ꢀH-5
C-3ꢀC-4ꢀC-5ꢀC-6
C-1¦ꢀC-4ꢀC-3ꢀH-3b
H-6aꢀC-6ꢀC-5ꢀH-5
H-5ꢀC-5ꢀC-1%ꢀH-1%
C-5ꢀC-1%ꢀC-2%ꢀOAc
AcO–C-1%ꢀC-2%ꢀC-3%
H-3aꢀC-3ꢀC-2ꢀMe-2
C-2ꢀC-1ꢀC-6ꢀC-5
Me-1ꢀC-1ꢀC-6ꢀH-6b
AcOꢀC-3%ꢀC-4%ꢀOAc
C-2%ꢀC-3%ꢀC-4%ꢀC-5%
51.7 C-1¦ꢀC-4ꢀC-5ꢀC-1%
60.6 C-1¦ꢀC-4ꢀC-3ꢀH-3a%
−158.1 C-4ꢀC-3ꢀC-2ꢀC-1
−41.4 H-6bꢀC-6ꢀC-5ꢀH-5
−139.7 AcOꢀC-1%ꢀC-2%ꢀOAc
66.0 C-5ꢀC-1%ꢀC-2%ꢀC-3%
59.0 C-1%ꢀC-2%ꢀC-3%ꢀOAc
−48.1 H-3bꢀC-3ꢀC-2ꢀMe-2
19.6 Me-1ꢀC-1ꢀC-6ꢀH-6a
78.0 AcO–C-2%ꢀC-3%ꢀC-4%
62.6 C-2%ꢀC-3%ꢀC-4%ꢀOAc
−174.9 AcOꢀC-4%ꢀC-5%ꢀOAc
70.1
−39.0
−62.0
−55.7
67.4
−167.7
−167.0
−178.1
C-3%ꢀC-4%ꢀC-5%ꢀOAc −174.1 C-2¦ꢀC-1¦ꢀC-4ꢀC-5
C-3¦ꢀC-2¦ꢀC-1¦ꢀC-4
C-2¦ꢀC-1¦ꢀC-4ꢀC-3
174.8 OꢀC-3¦ꢀC-2¦ꢀC-1¦
67.2 C-4¦ꢀOꢀC-3¦ꢀC-1¦
,
Table 3. Deviations (A) of the six carbons of the ring in
2a with respect to the average plane of C-3, C-2, C-1 and
C-6
NO2
NO2
C-1
C-2
C-3
C-4
C-5
C-6
−0.0026
0.0026
−0.0012
0.2784
−0.4589
−0.0011
COR4
C-3
C-2´´
C-3
H-1´´
C-5
H-1´´
H
H
S
R
C-5
COR4
C-2´´
H
H
6a, 8a, 10a
7a, 9a, 11a
R4 = Me, OMe
H
COR4
H
C-2´´
In agreement with this mechanism, the configuration at
C-4 in the starting material should not influence the
stereochemistry of the product. Thus, we have per-
formed the reaction between methyl acrylate and cis-5-
glyco-4-nitrocyclohexene 15a, to give the same product
as was obtained starting from 1a (Scheme 3).
C-5
C-3
C-5
C-3
H
H
R
S
H-1´´
COR4
H-1´´
C-2´´
NO2
NO2
6b, 8b, 10b
7b, 9b, 11b
When a,b-disubstituted electron-deficient alkenes were
used in Michael additions with 1a or 1b we obtained, in
Figure 4. Newmann projections (C-1¦–C-4) for adducts 6–11,
a,b.
NO2
base
NO2
NO2
R1
R1
R1
14a
R3
1a
R2
R3
1´´
R2
4
R1
NO2
2a
Scheme 2.
CH2CH2COOMe
NO2
NO2
NO2
R1
COOMe
COOMe
MeCN / DBU
MeCN / DBU
R1
R1
1a
2a
15a
Scheme 3.

R. Ballini et al. / Tetrahedron: Asymmetry 13 (2002) 1773–1787
1777
Newmann projections along C-1¦ꢀC-4 for the adducts
6–11, a,b.
3f and 4f, were prepared by a two-step process that
involved base-catalyzed deacetylation of the sugar side-
chain of 2a,b, 3b and 4b to yield 2c,d, 3d and 4d,
followed by oxidative cleavage of the deacetylated
sugar side-chains, thus affording the above cited
nitroaldehydes (Scheme 5).
On the other hand, when Michael additions of 1a or 1b
with dimethyl fumarate (or maleate) and methyl trans-
4-oxo-pentenoate, respectively, were carried out in the
presence of DBU (2.0 equiv.) instead of TMG, we
obtained cyclohexadienes 12 and 13,a,b. Furthermore,
these elimination products were also obtained by treat-
ment of ca. 1:1 mixtures of either adducts 6a, 7a, or 8b,
9b with 2.0 equiv. of DBU. As shown in Scheme 4
starting from 1a and dimethyl fumarate, we propose
that the Michael addition is followed by in situ elimina-
tion of nitrous acid, promoted by the presence of an
electron-withdrawing group in the b-position with
respect to the nitro group.21
Deacetylated compounds 2c, 2d, 3d and 4d were
obtained as crystalline solids, with IR bands for
hydroxyl (broad, 3510–3280 cm−1) and tertiary nitro
1
groups (ca. 1530 and 1340 cm−1). H NMR spectra in
DMSO-d6 showed five D2O-exchangeable signals (four
doublets and a triplet at 4–5 ppm), which were
attributed to hydroxyl groups. The resonances for the
H-5 protons appear at 2.70–2.73 ppm, with J5,6a and
J5,6b couplings (ca. 5 and 1 Hz, respectively) indicating
that the conformation of the cyclohexene rings in these
compounds are very similar to those of their precursors.
The exocyclic double bond in compounds 16a and 17a
(E,Z isomers, not isolated) should isomerize to the
more-stable conjugated cyclohexadienes 12a and 13a
[1¦(R) and 1¦(S) isomers)]. PM3 semiempirical calcula-
tions with Gaussian 94W22 for simplified model com-
pounds (R1ꢂCHOHꢀCH2OH) showed that structures as
12a, 13a were more stable than those as 16a, 17a by
about 9.2 Kcal/mol.
On examining the physical properties of the deacetyl-
ated compounds, the appreciable solubility of 2c and 2d
in solvents as distinct as water and chloroform was
somewhat surprising. Thus, to consider the possible
utility of these substances as non-ionic surfactants, their
surface tension was measured. However, the values we
found (50 mN/m for 2c and 68 mN/m for 2d, in 10−3
M
1
Data from the H NMR spectra of the nitrous acid
aqueous solutions) were not enough to permit their
elimination products 12 and 13,a,b indicate that the
conformations of their respective sugar side-chains are
very similar to those of the corresponding precursors.
The presence of a singlet (5.57–5.64 ppm) that has been
attributed to the olefinic proton H-3 of the cyclohexadi-
ene ring is of note. The configurations at C-1¦ in 12 and
13, a,b have been tentatively assigned on the basis of
deshielding effects for the H-5 protons; thus, in com-
pounds 13a and 13b [1¦(S)], where H-5 is closer to a
COOMe group than in 12a and 12b [1¦(R)], the signals
for this proton appear downfield by 0.34 and 0.29 ppm,
respectively. The 13C NMR spectra of 12a and 13a were
practically superimposable, showing the presence of
four olefinic carbons at 124.8–131.0 ppm.
commercial application.23
Nitroaldehydes 2e, 2f, 3f and 4f were oily compounds,
whose structural assignment was based on IR and
NMR spectroscopic data, as well as elemental analysis
of the solid 2,4-dinitrophenylhydrazone derivative 2g of
2e. Thus, each of the aldehydes showed an IR band at
1
2720 cm−1 (CHO), and signals in the H and 13C NMR
spectra that supported the presence of the formyl group
(a sharp singlet at l 9.6 ppm and a signal at l 199.3).
The signal for the H-5 protons appears as a triplet
(3.14–3.22 ppm) with J5,6a and J5,6b couplings between
5.3 and 5.7 Hz. These values agree with dihedral angles
H-6a–C-6–C-5–H-5 and H-6b–C-6–C-5–H-5 of ca. 33
and 130°, respectively, thus suggesting that the formyl
group of the cyclohexene ring should be in a disposition
close to equatorial.
As noted above, we obtained enantiomeric nitroalde-
hydes 2e,f. These compounds, as well as their analogues
H
CH2COOMe
C
NO2
R1
COOMe
COOMe
(- HNO2)
MeOOC
MeCN / DBU
NO2
R1
1a
6a, 7a
CH2COOMe
COOMe
CH2COOMe
COOMe
isomerization
R1
R1
16a, 17a
12a, 13a
Scheme 4.

1778
R. Ballini et al. / Tetrahedron: Asymmetry 13 (2002) 1773–1787
R3
R3
R3
R2
NO2
R2
NO2
R2
NO2
NaIO4
NaOMe
MeOH
OAc
OH
CHO
AcO
AcO
HO
HO
2e
OAc
OAc
OH
OH
2a
2c
R3
R2
R3
R3
R2
R2
NO2
NaIO4
NaOMe
MeOH
NO2
NO2
AcO
AcO
HO
HO
CHO
2f-4f
OAc
OAc
OAc
OH
OH
OH
2d-4d
2b-4b
Scheme 5.
3. Experimental
3.2. 1%,2%,3%,4%,5%-Penta-O-acetyl-1%-C-[(4R,5S)-1,2-
dimethyl-4-(2¦-methoxycarbonylethyl)-4-nitrocyclohex-1-
3.1. General
en-5-yl]- -galacto-pentitol, 2a
D
Solvents were evaporated under reduced pressure
below 40°C bath temperature. Melting points were
determined with an Electrothermal 8100 apparatus
and are uncorrected. Optical rotations were obtained
at 20 2°C with a Perkin–Elmer 241 polarimeter.
Reactions were monitored by thin-layer chromatogra-
phy (TLC) on precoated plates of Kieselgel 60 GF254
(Merck), with visualization of spots by UV light or
iodine vapour. Separations by flash column chro-
matography and preparative thin-layer chromatogra-
phy (p.TLC) were performed using Merck Kieselgel
60 (230–400 mesh ASTM) and plates (20×20×0.2 cm)
of Merck Kieselgel 60 PF254, respectively. Infrared
spectra were recorded in the range 4000–600 cm−1
with Perkin–Elmer 399 or Midac FT-IR spectropho-
tometers. NMR spectra were recorded at 20°C on a
Bruker spectrometer AM 400 (400.13 MHz for 1H,
100.62 MHz for 13C) with TMS or residual CHCl3/
DMSO as internal standards. NMR assignments were
confirmed by addition of deuterium oxide, homonu-
clear double-resonance experiments, and DEPT.
Chemical shifts are reported in l units (ppm) and
coupling constants (J) are reported in Hz. Chemical
ionization low and high resolution mass spectra (CI
MS and CI HRMS) were taken on a VG Autospec
spectrometer. Elemental analyses were determined
with a Leco CHNS 932 instrument by the Microanal-
ysis Service at the University of Extremadura, Spain.
All commercially available reagents were purchased
from Aldrich Chemical Co. and used without further
purification. Surface tension (kl) was determined by
the No¨uy’s ring method by using a Kru¨ss Tensiome-
ter.
To
a
solution of 1%,2%,3%,4%,5%-penta-O-acetyl-1%-C-
[(4S,5S)-1,2-dimethyl-4-nitrocyclohex-1-en-5-yl]-
D
-
galacto-pentitol 1a (3.00 g, 5.83 mmol) in acetonitrile (10
mL) was added methyl acrylate (0.60 mL, 6.69 mmol) and
DBU (1.00 mL, 6.69 mmol). After stirring for 24 h at room
temperature, the reaction mixture was poured onto ice
cold water (100 mL), neutralized with 1 M hydrochloric
acid, extracted with methylene chloride (3×20 mL) and
washedwithwater(2×20mL). Theorganiclayerwasdried
over anhydrous MgSO4 and the solvent was evaporated,
yielding the title compound as an oil which crystallized
from 96% ethanol (2.10 g, 60%): mp 125–127°C; Rf 0.62
(1:1 hexane/AcOEt); [h]D=+34.8 (c 1.15, CHCl3); wmax
(KBr) 2960, 2900, 2860 (CH), 1745 (CꢂO), 1540, 1365
(NO2), 1210, 1030 (CꢀO) cm−1; 1H NMR (CDCl3) l 5.23
(d, 1H, J2%,3%=10.0 Hz, H-2%), 5.22 (m, 1H, H-4%), 4.99 (d,
1H, J1%,5=10.4 Hz, H-1%), 4.92 (dd, 1H, J3%,4%=2.0 Hz,
H-3%), 4.28 (dd, 1H, J4%,5%a=4.1 Hz, J5%a,5%b=12.0 Hz,
H-5%a), 3.74 (dd, 1H, J4%,5%b=7.7 Hz, H-5%b), 3.62 (s, 3H,
COOCH3), 2.65 (dd, 1H, J5,6a=5.1 Hz, J5,6b=1.0 Hz,
H-5), 2.46 (br d, 1H, J3a,3b=17.8 Hz, H-3a), 2.37 (br d,
1H, J6a,6b=18.8 Hz, H-6a), 2.25 (m, 1H, H-1¦a), 2.14,
2.05, 2.04, 1.97, 1.93 (each s, each 3H, 5×OCOCH3), 2.13
(d, 1H, H-3b), 2.05 (m, 3H, H-1¦b, H-2¦a, H-2¦b), 2.02
(dd, 1H, H-6b), 1.65, 1.64 (each s, each 3H, CH3-1,
CH3-2); 13C NMR (CDCl3) l 172.4 (C-3¦), 170.6, 170.2,
169.7(OCOCH3), 123.9, 121.4(C-1, C-2), 88.6(C-4), 69.1,
68.3, 68.1 (C-1%, C-2%, C-3%, C-4%), 62.8 (C-5%), 51.9 (C-4¦),
40.3 (C-5), 33.6, 33.0 (C-3, C-6), 32.9 (C-2¦), 27.9 (C-1¦),
20.7, 20.6, 20.2 (OCOCH3), 18.9, 18.6 (CH3-1, CH3-2).
Anal. calcd for C27H39NO14: C, 53.90; H, 6.53; N, 2.33.
Found: C, 53.96; H, 6.59; N, 2.32%.

R. Ballini et al. / Tetrahedron: Asymmetry 13 (2002) 1773–1787
1779
3.3. 1%,2%,3%,4%,5%-Penta-O-acetyl-1%-C-[4S,5R)-1,2-
121.5 (C-1, C-2), 88.8 (C-4), 69.2 68.3 (C-1%, C-2%, C-3%,
C-4%), 62.8 (C-5%) 40.6 (C-5), 37.1 (C-2¦), 33.7, 32.0 (C-3,
C-6), 31.7 (C-1¦), 30.1 (C-4¦), 20.7, 20.6, 20.2
(OCOCH3), 19.1, 18.6 (CH3-1, CH3-2). Anal. calcd for
C27H39NO13: C, 55.38; H, 6.71; N, 2.39. Found: C,
55.40; H, 6.64; N, 2.33%.
dimethyl-4-(2¦-methoxycarbonylethyl)-4-nitrocyclohex-1-
en-5-yl]- -manno-pentitol, 2b
D
To
a
solution of 1%,2%,3%,4%,5%-penta-O-acetyl-1%-C-
[(4R,5R)-1,2-dimethyl-4-nitrocyclohex-1-en-5-yl]-
D
-
manno-pentitol 1b (3.00 g, 5.83 mmol) in aceto-nitrile
(10 mL) was added methyl acrylate (0.60 mL, 6.69
mmol) and DBU (1.00 mL, 6.69 mmol). After stirring
for 12 h at room temperature, the reaction mixture was
poured onto ice cold water (50 mL), yielding the title
compound as a white solid which was filtered, washed
on the filter with cold water and recrystallized from
96% ethanol (3.10 g, 89%): mp 179–181°C; Rf 0.63 (1:1
hexane/AcOEt); [h]D=+13.9 (c 0.56, CHCl3); wmax
(KBr) 2960, 2920, 2860 (CH), 1740 (CꢂO), 1650 (CꢂC),
3.5. 1%,2%,3%,4%,5%-Penta-O-acetyl-1%-C-[(4S,5R)-1,2-
dimethyl-4-nitro-4-(3¦-oxobutyl)cyclohex-1-en-5-yl]-
D-
manno-pentitol, 3b
Following the procedure described in Section 3.2, treat-
ment of a solution of 1b (3.00 g, 5.83 mmol) in acetoni-
trile (10 mL) with methyl vinyl ketone (0.44 mL, 5.27
mmol) and TMG (0.07 mL, 0.53 mmol) yielded the title
compound as an oil which crystallized from ethanol/
water and was recrystallized from the same solvent
system (2.20 g, 65%): mp 118–120°C; Rf 0.73 (1:1
hexane/AcOEt); [h]D=+12.1 (c 0.85, CHCl3); wmax
(KBr) 2980, 2920, 2860 (CH), 1745 (CꢂO ester), 1710
(CꢂO ketone) 1630 (CꢂC), 1530, 1370 (NO2), 1210,
1
1535, 1365 (NO2), 1210, 1060 (CꢀO) cm−1; H NMR
(CDCl3) l 5.53 (dd, 1H, J2%,3%=1.8 Hz, H-3%), 5.23 (dd,
1H, H-2%), 5.21 (dd, 1H, J1%,5=9.9 Hz, J1%,2%=3.9 Hz,
H-1%), 5.08 (ddd, 1H, J3%,4%=8.3 Hz, H-4%), 4.23 (dd, 1H,
J
J
4%,5%a=2.7 Hz, J5%a,5%b=12.7 Hz, H-5%a), 4.08 (dd, 1H,
4%,5%b=5.6 Hz, H-5%b), 3.65 (s, 3H, COOCH3), 2.97 (dd,
1
1040, 1060 (CꢀO) cm−1; H NMR (CDCl3) l 5.54 (dd,
1H, J5,6a=4.6 Hz, H-5), 2.52 (br d, 1H, J6a,6b=13.9 Hz,
H-6a), 2.48 (br d, 1H, J3a,3b=19.6 Hz, H-3a), 2.29 (m,
1H, H-2¦a), 2.20–1.95 (m, 3H, H-2¦b, H-1¦a, H-1¦b),
2.16 (br d, 1H, H-3b), 2.12, 2.07, 2.06, 2.00, 1.92 (each
s, each 3H, 5×OCOCH3), 2.00 (br d, 1H, H-6b), 1.68,
1.66 (each s, each 3H, CH3-1, CH3-2); 13C NMR
(CDCl3) l 172.4 (C-3¦), 170.5, 170.2, 169.9, 169.6
(OCOCH3), 123.6, 121.3 (C-1, C-2), 88.8 (C-4), 69.8,
69.0, 68.8, 66.7 (C-1%, C-2%, C-3%, C-4%), 61.7 (C-5%), 51.9
(C-4¦), 40.0 (C-5), 33.7, 32.7 (C-3, C-6), 32.4 (C-2¦),
27.9 (C-1¦), 20.7, 20.4, 20.2 (OCOCH3), 19.2, 18.5
(CH3-1, CH3-2). Anal. calcd for C27H39NO14: C, 53.90;
H, 6.53; N, 2.33. Found: C, 53.99; H, 6.56; N, 2.33%.
1H, J2%,3%=1.9 Hz, H-3%), 5.23 (dd, 1H, H-2%), 5.21 (dd,
1H, J1%,5=9.9 Hz, J1%,2%=4.0 Hz, H-1%), 5.09 (ddd, 1H,
J3%,4%=8.5 Hz, H-4%), 4.23 (dd, 1H, J4%,5%a=2.7 Hz,
J
5%a,5%b=12.5 Hz, H-5%a), 4.09 (dd, 1H, J4%,5%b=5.4 Hz,
H-5%b), 2.96 (dd, 1H, J5,6a=4.1 Hz, H-5), 2.53 (m, 1H,
6a,6b=18.7 Hz, H-6a), 2.48 (d, 1H, J3a,3b=19.6 Hz,
J
H-3a), 2.43 (m, 1H, J1¦,2¦a=7.3 Hz, H-2¦a), 2.22 (m,
1H, J2¦a,2¦b=15.7 Hz, J1¦,2¦b=7.3 Hz, H-2¦b), 2.14 (d,
1H, H-3b), 2.13, 2.12, 2.07, 2.06, 2.00, 1.92 (each s,
each 3H, COCH3 and 5×OCOCH3), 2.10 (m, 2H, H-
1¦a, H-1¦b), 1.98 (m, 1H, H-6b), 1.67, 1.65 (each s, each
3H, CH3-1, CH3-2); 13C NMR (CDCl3) l 198.9 (C-3¦),
170.6, 170.2, 170.0, 169.6 (OCOCH3), 123.6, 121.4 (C-
1, C-2), 88.9 (C-4), 69.9, 69.0, 68.7, 66.7 (C-1%, C-2%,
C-3%, C-4%), 61.8 (C-5%), 40.2 (C-5), 37.1 (C-2¦), 33.9,
32.7 (C-3, C-6), 31.1 (C-1¦), 30.2 (C-4¦), 20.8, 20.5, 20.3
(OCOCH3), 19.3, 18.6 (CH3-1, CH3-2). Anal. calcd for
C27H39NO13: C, 55.38; H, 6.71; N, 2.39. Found: C,
55.26; H, 6.78; N, 2.38%.
3.4. 1%,2%,3%,4%,5%-Penta-O-acetyl-1%-C-[(4R,5S)-1,2-
dimethyl-4-nitro-4-(3¦-oxobutyl)cyclohex-1-en-5-yl]-
D-
galacto-pentitol, 3a
Following the procedure described in Section 3.2, treat-
ment of a solution of 1a (3.00 g, 5.83 mmol) in acetoni-
trile (10 mL) with methyl vinyl ketone (0.52 mL, 6.2
mmol) and TMG (0.07 mL, 0.53 mmol) led to the title
compound as a white solid which was filtered and
washed on the filter with cold water (2.80 g, 82%): mp
133−135°C; Rf 0.57 (1:1 hexane/AcOEt); [h]D=+22.5 (c
0.51, CHCl3); wmax (KBr) 2980, 2920, 2860 (CH), 1740
(CꢂO ester), 1710 (CꢂO ketone) 1535, 1360 (NO2),
3.6. 1%,2%,3%,4%,5%-Penta-O-acetyl-1%-C-[(4R,5S)-4-(2¦-
cyanoethyl)-1,2-dimethyl-4-nitrocyclohex-1-en-5-yl]-D-
galacto-pentitol, 4a
Following the procedure described in Section 3.2, treat-
ment of a solution of 1a (3.00 g, 5.83 mmol) in acetoni-
trile (10 mL) with acrylonitrile (0.41 mL, 6.69 mmol)
and TMG (0.07 mL, 0.53 mmol) led to the title com-
pound as an oil which crystallized from ethanol/water
and was recrystallized from 96% ethanol (1.94 g, 60%):
mp 132−134°C; Rf 0.56 (1:1 hexane/AcOEt); [h]D=
+34.0 (c 0.5, CHCl3); wmax (KBr) 2960, 2920, 2860 (CH),
2250 (CꢁN), 1740 (CꢂO), 1650 (CꢂC), 1540, 1365
1
1205, 1020 (CꢀO) cm−1; H NMR (CDCl3) l 5.26 (d,
1H, J2%,3%=9.7 Hz, H-2%), 5.25 (m, 1H, H-4%), 5.00 (d,
1H, J1%,5=10.5 Hz, H-1%), 4.93 (dd, 1H, J3%,4%=1.9 Hz,
H-3%), 4.30 (dd, J4%,5%a=4.1 Hz, J5%a,5%b=11.9 Hz, H-5%a),
3.76 (dd, 1H, J4%,5%b=7.7 Hz, H-5%b), 2.67 (dd, 1H,
1
J5,6a=4.9 Hz, J5,6b=1 Hz, H-5), 2.46 (br d, 1H, J6a,6b
=
(NO2), 1200, 1050 (CꢀO) cm−1; H NMR (CDCl3) l
18.3 Hz, H-6a), 2.42 (m, 1H, H-3a), 2.38 (m, 1H,
H-2¦a), 2.2–2.0 (m, 5H, H-3b, H-6b, H-2¦b, H-1¦a,
H-1¦b), 2.16, 2.10, 2.07, 2.06, 1.99, 1.95 (each s, each
3H, COCH3 and 5×OCOCH3), 1.67, 1.65 (each s, each
3H, CH3-1, CH3-2); 13C NMR (CDCl3) l 206.2 (C-3¦),
170.6, 170.5, 170.4, 170.3, 169.8 (OCOCH3), 123.8,
5.25 (dd, 1H, J2%,3%=9.9 Hz, H-2%), 5.25 (m, 1H, H-4%),
5.00 (dd, 1H, J1%,5=10.4 Hz, J1%,2%=0.9 Hz, H-1%), 4.94
(dd, 1H, J3%,4%=2.2 Hz, H-3%), 4.31 (dd, 1H, J4%,5%a=4.1
Hz, J5%a,5%b=12.0 Hz, H-5%a), 3.75 (dd, 1H, J4%,5%b=7.7
Hz, H-5%b), 2.68 (dd, 1H, J5,6a=5.4 Hz, H-5), 2.54 (br
d, 1H, J3a,3b=17.5 Hz, H-3a), 2.34 (br d, 1H, J6a,6b
=

1780
R. Ballini et al. / Tetrahedron: Asymmetry 13 (2002) 1773–1787
19.2 Hz, H-6a), 2.30–2.05 (m, 4H, H-1¦a, H-1¦b, H-2¦a,
H-2¦b), 2.23 (br d, 1H, H-3b), 2.16, 2.07, 2.06, 2.00,
1.95 (each s, each 3H, 5×OCOCH3), 2.10 (d, 1H, H-6b),
2.02 (dd, 1H, H-6b), 1.70, 1.69 (each s, each 3H, CH3-1,
CH3-2); 13C NMR (CDCl3) l 170.6, 170.5, 170.4, 170.2,
169.7 (OCOCH3), 123.7, 121.6 (C-1, C-2), 118.0 (C-3¦),
88.4 (C-4), 68.9, 68.1 (C-1%, C-2%, C-3%, C-4%), 62.7 (C-5%),
40.1 (C-5), 33.4, 33.2, 32.9 (C-3, C-6, C-1¦), 20.7, 20.6,
20.1 (OCOCH3), 19.1, 18.5 (CH3-1, CH3-2), 11.8 (C-
2¦). Anal. calcd for C26H36N2O12: C, 54.92; H, 6.38; N,
4.92. Found: C, 54.98; H, 6.42; N, 4.88%.
(CDCl3) l 200.2 (C-3¦), 170.6, 170.2, 169.8, 169.7
(OCOCH3), 123.8, 121.2 (C-1, C-2), 88.4 (C-4), 68.9,
68.5, 68.2 (C-1%, C-2%, C-3%, C-4%), 62.6 (C-5%), 40.0 (C-5),
37.4 (C-2¦), 33.6, 32.3 (C-3, C-6), 29.7 (C-1¦), 20.5,
20.4, 20.0 (OCOCH3), 19.3, 18.5 (CH3-1, CH3-2).
3.9. 1%,2%,3%,4%,5%-Penta-O-acetyl-1%-C-[(4S,5R)-4-(2¦-
formylethyl)-1,2-dimethyl-4-nitrocyclohex-1-en-5-yl]-D-
manno-pentitol, 5b
Following the procedure described in Section 3.2, treat-
ment of a solution of 1b (3.00 g, 5.83 mmol) in acetoni-
trile (10 mL) with acrolein (1.4 mL, 20.94 mmol) and
triethylamine (1.3 mL, 9.3 mmol), led to the title com-
pound as an oil which was purified by column chro-
matography using 3:1 hexane/AcOEt as eluent (1.2 g,
36%): Rf 0.58 (1:1 hexane/AcOEt); [h]D=+19.4 (c 0.92,
CHCl3); wmax (film) 3010, 2920, 2860 (CH), 2720 (CH
aldehyde), 1740 (CꢂO), 1650 (CꢂC), 1535, 1360 (NO2),
3.7. 1%,2%,3%,4%,5%-Penta-O-acetyl-1%-C-[(4S,5R)-4-(2¦-
cyanoethyl)-1,2-dimethyl-4-nitrocyclohex-1-en-5-yl]-D-
manno-pentitol, 4b
Following the procedure described in Section 3.2, treat-
ment of a solution of 1b (3.00 g, 5.83 mmol) in acetoni-
trile (10 mL) with acrylonitrile (0.41 mL, 6.69 mmol)
and TMG (0.07 mL, 0.53 mmol), led to the title com-
pound as an oil which crystallized from ethanol/water
and was recrystallized from 96% ethanol (2.82 g, 85%):
mp 113–115°C; Rf 0.70 (1:1 hexane/AcOEt); [h]D=
+19.3 (c 0.57, CHCl3); wmax (KBr) 2980, 2920, 2860
(CH), 2250 (CꢁN), 1735 (CꢂO), 1635 (CꢂC), 1540, 1365
(NO2), 1210, 1050, 1040 (CꢀO) cm−1; 1H NMR (CDCl3)
l dd, 1H, J2%,3%=1.6 Hz, H-3%), 5.23 (dd, 1H, H-2%), 5.21
(dd, 1H, J1%,5=9.4 Hz, J1%,2%=3.8 Hz, H-1%), 5.09 (ddd,
1H, J3%,4%=8.2 Hz, H-4%), 4.24 (dd, 1H, J4%,5%a=2.6 Hz,
1
1210, 1040, (CꢀO) cm−1; H NMR (CDCl3) l 9.72 (s,
1H, H-3¦), dd, 1H, J2%,3%=1.6 Hz, H-3%), 5.22 (dd, 1H,
H-2%), 5.20 (dd, 1H, J1%,5=9.0 Hz, J1%,2%=3.9 Hz, H-1%),
5.08 (ddd, 1H, J3%,4%=8.3 Hz, H-4%), 4.22 (dd, 1H,
J
J
4%,5%a=2.7 Hz, J5%a,5%b=12.6 Hz, H-5%a), 4.08 (dd, 1H,
4%,5%b=5.5 Hz, H-5%b), 2.97 (dd, 1H, J5,6a=4.4 Hz,
H-5), 2.60–2.40 (m, 3H, H-2¦a, H-3a, H-6a), 2.28 (ddd,
1H, J2¦a,2¦b=18.3 Hz, J1¦b,2¦b=9.7 Hz, H-2¦b), 2.15 (m,
2H, H-1¦a, H-1¦b), 2.14 (m, 1H, H-3b) 2.11, 2.06, 2.05,
2.00, 1.92 (each s, each 3H, 5×OCOCH3), 2.06 (m, 1H,
H-6b), 1.67, 1.65 (each s, each 3H, CH3-1, CH3-2); 13C
NMR (CDCl3) l 199.3 (C-3¦), 170.5, 170.1, 169.9, 169.5
(OCOCH3), 123.5, 121.3 (C-1, C-2), 88.6 (C-4), 69.7,
68.9, 68.7, 66.6 (C-1%, C-2%, C-3%, C-4%), 61.6 (C-5%), 39.5
(C-5), 37.7 (C-2¦), 33.8 (C-3), 32.6 (C-6), 29.4 (C-1¦),
20.6, 20.3, 20.1 (OCOCH3), 19.1, 18.4 (CH3-1, CH3-2).
J5%a,5%b=12.6 Hz, H-5%a), 4.09 (dd, 1H, J4%,5%b=5.4 Hz,
H-5%b), 2.99 (dd, 1H, J5,6a=4.4 Hz, H-5), 2.53 (br d,
1H, H-6a), 2.48 (br d, 1H, H-3a), 2.4–2.0 (m, 6H,
H-1¦a, H-1¦b, H-2¦a, H-2¦b, H-3a, H-3b), 2.12, 2.07,
2.06, 2.00, 1.92 (each s, each 3H, 5×OCOCH3), 1.71,
1.70 (each s, each 3H, CH3-1, CH3-2); 13C NMR
(CDCl3) l 170.5, 170.0, 169.6 (OCOCH3), 123.4, 121.6
(C-1, C-2), 118.1 (C-3¦), 88.4 (C-4), 69.6, 68.9, 68.7,
66.6 (C-1%, C-2%, C-3%, C-4%), 61.6 (C-5%), 39.6 (C-5), 33.5,
33.0 (C-3, C-6), 32.6 (C-1¦), 20.7, 20.4, 20.2
(OCOCH3), 19.1, 18.4 (CH3-1, CH3-2), 11.8 (C-2¦).
Anal. calcd for C26H36N2O12: C, 54.92; H, 6.38; N,
4.92. Found: C, 54.97; H, 6.24; N, 4.98%.
3.10. 1%,2%,3%,4%,5%-Penta-O-acetyl-1%-C-[(4R,5S)-1,2-
dimethyl-4-[(1¦R)-1¦,2¦-dimethoxycarbonylethyl]-4-nitro-
cyclohex-1-en-5-yl]- -galacto-pentitol, 6a and
D
1%,2%,3%,4%,5%-penta-O-acetyl-1%-C-[(4R,5S)-1,2-dimethyl-
4-[(1¦S)-1¦,2¦-dimethoxycarbonylethyl]-4-nitrocyclohex-
1-en-5-yl]- -galacto-pentitol, 7a
D
3.8. 1%,2%,3%,4%,5%-Penta-O-acetyl-1%-C-[(4R,5S)-4-(2¦-
To a solution of 1a (1.00 g, 1.94 mmol) in acetonitrile
(4 mL) was added either dimethyl fumarate or dimethyl
maleate (0.32 g, 2.23 mmol) and TMG (0.28 mL, 2.23
mmol) at 0°C. After stirring for 24 h at room tempera-
ture, the reaction mixture was poured onto cold water
(50 mL) and neutralized with 1 M hydrochloric acid,
yielding a ca. 1:1 mixture of the title compounds as a
white solid, which was filtered and washed on the filter
with cold water (1.27 g, quantitative). Anal. calcd for
C29H41NO16: C, 52.80; H, 6.26; N, 2.12. Found: C,
53.10; H, 6.59; N, 2.32%. Preparative thin-layer chro-
matography (1.0:1.5 petroleum ether/ethyl ether) of the
mixture afforded samples in which each of the title
compounds was clearly predominant. Data for 6a: Rf
0.47 (1:1 hexane/AcOEt); wmax (KBr) 2990, 2950 (CꢀH),
1740 (CꢂO), 1540, 1370 (NO2), 1220, 1040 (CꢀO) cm−1;
1H NMR (CDCl3) l 5.31 (d, 1H, J2%,3%=10.0 Hz, H-2%),
5.27 (m, 1H, H-4%), 5.02 (d, 1H, J1%,5=10.0 Hz, H-1%),
formylethyl)-1,2-dimethyl-4-nitrocyclohex-1-en-5-yl]-D-
galacto-pentitol, 5a
Following the procedure described in Section 3.2, treat-
ment of a solution of 1a (3.00 g, 5.83 mmol) in acetoni-
trile (10 mL) with acrolein (0.42 mL, 6.2 mmol) and
TMG (0.07 mL, 0.53 mmol) led to the title compound
as an oil which was purified by column chromatogra-
phy using 3:1 hexane/AcOEt as eluent (1.47 g, 44%): Rf
0.66 (1:1 hexane/AcOEt); [h]D=+24.6 (c 0.50, CHCl3);
wmax (film) 2960, 2920, 2860 (CH), 2720 (CH aldehyde),
1745 (CꢂO), 1630 (CꢂC), 1535, 1360 (NO2), 1210, 1020,
1
(CꢀO) cm−1; H NMR (CDCl3) l 9.71 (s, 1H, H-3¦),
5.25 (m, 1H, H-4%), 4.31 (dd, 1H, J4%,5%a=3.9 Hz,
J
5%a,5%b=12.0 Hz, H-5%a), 3.76 (dd, 1H, J4%,5%b=7.8 Hz,
H-5%b), 2.67 (dd, 1H, J5,6a=5.3 Hz, H-5), 2.12, 2.08,
2.04, 2.00, 1.94 (each s, each 3H, 5×OCOCH3), 1.68,
1.66 (each s, each 3H, CH3-1, CH3-2); 13C NMR

R. Ballini et al. / Tetrahedron: Asymmetry 13 (2002) 1773–1787
1781
pounds was clearly predominant. Data for 6b: Rf 0.42
(1:1 hexane/AcOEt; wmax (Nujol) 3010, 2970, 2950
4.94 (dd, 1H, J3%,4%=2.1 Hz, H-3%), 4.32 (dd, 1H, J4%,5%a
5.1 Hz, J5%a,5%b=12.0 Hz, H-5%a), 3.78 (dd, 1H, J4%,5%b
7.7 Hz, H-5%b), 3.71, 3.65 (each s, each 3H,
CH2COOCH3, CHCOOCH3), 3.36 (dd, 1H, H-1¦), 3.05
(dd, 1H, J5,6a=5.5 Hz, J5,6b=1 Hz, H-5), 2.63 (dd, 1H,
=
=
(CꢀH), 1740 (CꢂO), 1540, 1365 (NO2), 1220, 1060
1
(CꢀO) cm−1; H NMR (CDCl3) l 5.54 (dd, 1H, J3%,4%
=
8.5 Hz, H-3%), 5.27 (dd, 1H, J2%,3%=1.6 Hz, H-2%), 5.23
(dd, 1H, J1%,5=9.0 Hz, J1%,2%=3.9 Hz, H-1%), 5.11 (m, 1H,
H-4%), 4.24 (dd, 1H, J4%,5%a=2.6 Hz, J5%a,5%b=12.5 Hz,
H-5%a), 4.07 (dd, 1H, J4%,5%b=5.8 Hz, H-5%b), 3.68, 3.66
(each s, each 3H, CH2COOCH3, CHCOOCH3), 3.29
(dd, 1H, H-1¦), 3.11 (dd, 1H, J5,6a=5.3 Hz, H-5), 3.07
(dd, 1H, J1¦,2¦a=12.0 Hz, J2¦a,2¦b=17.5 Hz, H-2¦a), 2.80
J1¦,2¦a=10.9 Hz, J2¦a,2¦b=17.0 Hz, H-2¦a), 2.48 (br d,
1H, J3a,3b=18.1 Hz, H-3a), 2.30 (br d, 1H, H-3b),
2.2–2.1.9 (m, 2H, H-6a, H-6b), 2.15, 2.09, 2.08, 2.00,
1.95 (each s, each 3H, 5×OCOCH3), 1.69, 1.65 (each s,
each 3H, CH3-1, CH3-2); 13C NMR (CDCl3) l 171.8,
170.6, 169.7 (OCOCH3, CH2COOCH3, CHCOOCH3),
124.4, 122.8 (C-1, C-2), 90.0 (C-4), 69.4, 67.3 (C-1%,
C-2%, C-3%, C-4%), 62.7 (C-5%), 52.8, 52.1 (CH2COOCH3,
CHCOOCH3), 45.4 (C-5), 38.1 (C-1¦), 34.0, 33.7 (C-3,
C-6), 31.1 (C-2¦), 20.7, 20.0 (OCOCH3), 18.6, 18.4
(CH3-1, CH3-2). Data for 7a: Rf 0.43 (1:1 hexane/
AcOEt); wmax (KBr) 2990, 2950 (CꢀH), 1740 (CꢂO),
(dd, 1H, J1¦,2¦b=2.3 Hz, H-2¦b), 2.53 (br d, 1H, J6a,6b
=
18.2 Hz, H-6a), 2.42 (br d, 1H, J3a,3b=17.0 Hz, H-3a),
2.32 (d, 1H, H-6b), 2.15, 2.07, 2.05, 1.99, 1.90 (each s,
each 3H, 5×OCOCH3), 2.00 (d, 1H, H-3b), 1.69 (s, 6H,
CH3-1, CH3-2); 13C NMR (CDCl3) l 172.1, 171.8,
170.5, 170.2, 169.6 (COOCH3, OCOCH3), 124.2, 120.8
(C-1, C-2), 88.1 (C-4), 69.2, 68.7, 68.6, 66.6 (C-1%, C-2%,
C-3%, C-4%), 61.8 (C-5%), 52.5, 52.1 (COOCH3), 45.8
(C-5), 37.0 (C-1¦), 33.8, 33.6 (C-3, C-6), 31.3 (C-2¦),
20.7, 20.4, 20.2, 20.1 (OCOCH3), 19.1, 18.4 (CH3-1,
CH3-2). Data for 7b: Rf 0.47 (1:1 hexane/AcOEt); wmax
(Nujol) 3010, 2970, 2950 (CꢀH), 1740 (CꢂO), 1545,
1
1540, 1370 (NO2), 1220, 1040 (CꢀO) cm−1; H NMR
(CDCl3) l 5.27 (m, 1H, H-4%), 5.23 (d, 1H, J2%,3%=10.1
Hz, H-2%), 5.02 (d, 1H, J1%,5=10.4 Hz, H-1%), 4.94 (dd,
1H, J3%,4%=2.1 Hz, H-3%), 4.33 (dd, 1H, J4%,5%a=5.1 Hz,
J5%a,5%b=12.0 Hz, H-5%a), 3.77 (dd, 1H, J4%,5%b=7.7 Hz,
H-5%b), 3.67 (s, 6H, CH2COOCH3 and CHCOOCH3),
1
1370 (NO2), 1220, 1060 (CꢀO) cm−1; H NMR (CDCl3)
3.26 (dd, 1H, H-1¦), 3.01 (dd, 1H, J1¦,2¦a=12.1 Hz,
l 5.54 (dd, 1H, J3%,4%=8.5 Hz, H-3%), 5.27 (dd, 1H,
J2¦a,2¦b=17.2 Hz, H-2¦a), 2.82 (m, 1H, H-5), 2.60 (dd,
J2%,3%=1.6 Hz, H-2%), 5.23 (dd, 1H, J1%,5=9.0 Hz, J1%,2%
4.0 Hz, H-1%), 5.08 (m, 1H, H-4%), 4.19 (dd, 1H, J4%,5%a
=
=
1H, J1¦,2¦b=2.2 Hz, H-2¦b), 2.55 (br d, 1H, J3a,3b=19.2
Hz, H-3a), 2.36 (br d, 1H, H-3b), 2.2–1.9 (m, 2H, H-6a,
H-6b), 2.13, 2.06, 2.05, 2.00, 1.95 (each s, each 3H,
5×OCOCH3), 1.70 (s, 6H, CH3-1, CH3-2); 13C NMR
2.6 Hz,
J5%a,5%b=12.5 Hz, H-5%a), 4.08 (dd, 1H,
J4%,5%b=5.6 Hz, H-5%b), 3.81, 3.66 (each s, each 3H,
CH2COOCH3, CHCOOCH3), 3.37 (dd, 1H, H-1¦), 3.26
(dd, 1H, J5,6a=5.3 Hz, H-5), 2.98 (br d, 1H, J6a,6b=19.7
Hz, H-6a), 2.65 (dd, 1H, J1¦,2¦a=11.0 Hz, J2¦a,2¦b=17.1
Hz, H-2¦a), 2.50 (br d, 1H, J3a,3b=18.2 Hz, H-3a), 2.48
(dd, 1H, J1¦,2¦b=3.5 Hz, H-2¦b), 2.32 (br d, 1H, H-3b),
2.09. 2.07, 2.04, 2.01, 1.90 (each s, each 3H, 5×
OCOCH3), 2.04 (d, 1H, H-6b), 1.68, 1.63 (each s, each
3H, CH3-1, CH3-2); 13C NMR (CDCl3) l 171.8, 170.5,
170.2, 169.9, 169.6 (COOCH3, OCOCH3), 122.7, 122.0
(C-1, C-2), 90.3 (C-4), 70.0, 68.8, 68.5, 66.4 (C-1%, C-2%,
C-3%, C-4%), 61.8 (C-5%), 52.8, 52.1 (COOCH3), 45.2
(C-5), 38.0 (C-1¦), 33.8, 33.6 (C-3, C-6), 31.2 (C-2¦),
20.7, 20.4, 20.2, 20.1 (OCOCH3), 19.1, 18.4 (CH3-1,
CH3-2).
(CDCl3)
l
171.7, 170.5, 169.6, (OCOCH3,
CH2COOCH3, CHCOOCH3), 124.4, 122.8 (C-1, C-2),
88.0 (C-4), 68.8, 67.5 (C-1%, C-2%, C-3%, C-4%), 62.8 (C-5%),
52.4, 52.0 (CH2COOCH3, CHCOOCH3), 46.0 (C-5),
37.2 (C-1¦), 33.9, 33.7 (C-3, C-6), 32.7 (C-2¦), 20.7, 20.5
(OCOCH3), 19.0, 18.4 (CH3-1, CH3-2).
3.11. 1%,2%,3%,4%,5%-Penta-O-acetyl-1%-C-[(4S,5R)-1,2-
dimethyl-4-[(1¦R)-1¦,2¦-dimethoxycarbonylethyl]-4-nitro-
cyclohex-1-en-5-yl]- -manno-pentitol, 6b and
1%,2%,3%,4%,5%-penta-O-acetyl-1%-C-[(4S,5R)-1,2-dimethyl-
4-[(1¦S)-1¦,2¦-dimethoxycarbonylethyl]-4-nitrocyclohex-
1-en-5-yl]- -manno-pentitol, 7b
D
D
Following the procedure described in Section 3.2, treat-
ment of a solution of 1b (0.40 g, 0.78 mmol) in acetoni-
trile (1.5 mL) with either dimethyl fumarate or dimethyl
maleate (0.13 g, 0.90 mmol) and TMG (0.01 mL, 0.09
mmol) at 0°C, led to an oil that contained the title
compounds (ca. 1:1 ratio) together with other minor
unidentified products. Purification of this crude by
column chromatography, using 3:2 cyclohexane/AcOEt
as eluent, yielded a ca. 1:1 mixture of 6b and 7b as a
colourless oil (0.365 g, 71%). CI MS m/z (rel. int.): 660
([M+H]+, 24%), 600 (M−OAc, 10), 554 (M−OAc−NO2,
15), 539 (M−2HOAc, 18), 493 (M−NO2−2HOAc, 21),
461 (10), 433 (63), 373 (80), 341 (10), 331 (34), 313
(100); CI HRMS calcd for C29H41NO16+H 660.2503.
Found (M+H)+ 660.2503. Preparative thin-layer chro-
matography of the mixture (1:1 hexane/AcOEt)
afforded oily samples in which each of the title com-
3.12. 1%,2%,3%,4%,5%-Penta-O-acetyl-1%-C-[(4S,5R)-1,2-
dimethyl-4-[(1¦R)-1¦-methoxycarbonyl-3¦-oxobutyl]-4-
nitrocyclohex-1-en-5-yl]- -galacto-pentitol, 8a and
D
1%,2%,3%,4%,5%-penta-O-acetyl-1%-C-[(4S,5R)-1,2-dimethyl-
4-[(1¦S)-1¦-methoxycarbonyl-3¦-oxobutyl]-4-nitrocyclo-
hex-1-en-5-yl]- -galacto-pentitol, 9a
D
Following the procedure described in Section 3.2, treat-
ment of a solution of 1a (0.40 g, 0.78 mmol) in acetoni-
trile (1.5 mL) with methyl trans-4-oxo-pentenoate (0.12
g, 0.90 mmol) and TMG (0.01 mL, 0.09 mmol) at 0°C
led to an oil that contained the title compounds (ca. 1:1
ratio) together with other minor unidentified products.
Purification of this crude by column chromatography,
using 3:2 cyclohexane/AcOEt as eluent, yielded a ca.
1:1 mixture of 8a and 9a as a colourless oil (0.42 g,
83%). Preparative thin-layer chromatography of the

1782
R. Ballini et al. / Tetrahedron: Asymmetry 13 (2002) 1773–1787
mixture (1:1 hexane/AcOEt) afforded oily samples in
which each of the title compounds was clearly pre-
dominant. Data for 8a: Rf 0.49 (1:1 hexane/AcOEt);
wmax (Nujol) 3010, 2950, 2920, 2865 (C-H), 1745 (CꢂO
ester), 1710 (CꢂO ketone) 1540, 1365 (NO2), 1215,
1050, 1040 (CꢀO) cm−1; 1H NMR (CDCl3) l 5.30
(dd, 1H, J2%,3%=9.1 Hz, H-2%), 5.26 (m, 1H, H-4%), 5.01
(dd, 1H, J1%,5=9.0 Hz, J1%,2%=1.0 Hz, H-1%), 4.94 (dd,
1H, J3%,4%=2.3 Hz, H-3%), 4.32 (dd, 1H, J4%,5%a=3.7 Hz,
int.): 644 ([M+H]+, 10%), 597 (M−NO2, 30), 584 (M−
COOCH3, 24), 537 (M−NO2−HOAc, 40), 505 (22),
477 (47), 417 (100), 357 (94); CI HRMS calcd for
C29H41NO15+H 644.2554. Found (M+H)+ 644.2545.
Preparative thin-layer chromatography of the mixture
(1:1 hexane/AcOEt) afforded oily samples in which
each of the title compounds was clearly predominant.
Data for 8b: Rf 0.42 (1:1 hexane/AcOEt); wmax (Nujol)
3020, 2950, 2920, 2860 (CꢀH), 1745 (CꢂO ester), 1710
(CꢂO ketone), 1545, 1365 (NO2), 1215, 1055, 1040
(CꢀO) cm−1; 1H NMR (CDCl3) l 5.54 (dd, 1H,
J3%,4%=8.2 Hz, H-3%), 5.23 (dd, 1H, J2%,3%=1.8 Hz, H-
2%), 5.21 (dd, 1H, J1%,5=10.0 Hz, J1%,2%=3.8 Hz, H-1%),
5.11 (ddd, 1H, H-4%), 4.24 (dd, 1H, J4%,5%a=2.7 Hz,
J5%a,5%b=11.7 Hz, H-5%a), 3.76 (dd, 1H, J4%,5%b=7.9 Hz,
H-5%b), 3.68 (s, 3H, COOCH3), 3.38 (dd, 1H, H-1¦),
3.00 (m, 1H, H-5), 2.80 (dd, 1H, J1¦,2¦a=10.4 Hz,
J2¦a,2¦b=18.2 Hz, H-2¦a), 2.48 (br d, 1H, J3a,3b=18.5
Hz, H-3a), 2.43 (dd, 1H, J1¦,2¦b=3.7 Hz, H-2¦b), 2.25
(br d, 1H, H-3b), 2.20–1.90 (m, 2H, H-6a, H-6b),
2.17, 2.15, 2.09, 2.07, 1.99, 1.95 (each s, each 3H,
COCH3, 5×OCOCH3), 1.70, 1.62 (each s, each 3H,
CH3-1, CH3-2); 13C NMR (CDCl3) l 205.7 (C-3¦),
170.7, 170.6, 170.3, 169.9 (OCOCH3, COOCH3),
123.0, 122.2 (C-1, C-2), 90.3 (C-4), 69.6, 68.4, 68.3,
68.2 (C-1%, C-2%, C-3%, C-4%), 62.9 (C-5%), 52.5
(COOCH3), 44.8 (C-5), 40.2 (C-2¦), 38.3 (C-1¦), 34.1,
34.0 (C-3, C-6), 30.2 (C-4¦), 20.9, 20.6, 20.4
(OCOCH3), 19.3, 18.6 (CH3-1, CH3-2). Data for 9a:
Rf 0.47 (1:1 hexane/AcOEt); wmax (Nujol) 3020, 2950,
2920, 2860 (CꢀH), 1745 (CꢂO ester), 1715 (CꢂO
ketone) 1545, 1365 (NO2), 1215, 1055, 1040 (CꢀO)
cm−1; 1H NMR (CDCl3) l 5.27 (m, 1H, H-4%), 5.20
(dd, 1H, J2%,3%=9.8 Hz, H-2%), 5.00 (dd, 1H, J1%,5=10.7
Hz, J1%,2%=1.0 Hz, H-1%), 4.92 (dd, 1H, J3%,4%=2.2 Hz,
H-3%), 4.32 (dd, 1H, J4%,5%a=4.5 Hz, J5%a,5%b=11.2 Hz,
H-5%a), 3.75 (dd, 1H, J4%,5%b=7.9 Hz, H-5%b), 3.61 (s,
3H, COOCH3), 3.29 (dd, 1H, H-1¦), 3.09 (dd, 1H,
J5%a,5%b=12.5 Hz, H-5%a), 4.08 (dd, 1H, J4%,5%b=5.6 Hz,
H-5%b), 3.63 (s, 3H, COOCH3), 3.34 (dd, 1H, H-1¦),
3.27 (dd, 1H, J1¦,2¦a=11.5 Hz, J2¦a,2¦b=17.3 Hz, H-
2¦a), 3.07 (m, 1H, J5,6a=5.9 Hz, J5,6b=1 Hz, H-5),
2.87 (dd, 1H, J1¦,2¦b=2.0 Hz, H-2¦b), 2.57 (br d, 1H,
J3a,3b=17.9 Hz, H-3a), 2.40 (br d, 1H, H-3b), 2.20–
1.90 (m, 2H, H-6a, H-6b), 2.17, 2.09, 2.06, 2.04, 1.98,
1.90 (each s, each 3H, COCH3 and 5×OCOCH3), 1.69
and 1.68 (each s, each 3H, CH3-1, CH3-2); 13C NMR
(CDCl3) l 206.4 (C-3¦), 170.7, 170.5, 170.2, 169.9,
169.6 (OCOCH3, COOCH3), 124.3, 120.7 (C-1, C-2),
88.4 (C-4), 69.2, 68.7, 66.7 (C-1%, C-2%, C-3%, C-4%),
61.8 (C-5%), 52.5 (COOCH3), 44.8 (C-5), 40.5 (C-2¦),
37.0 (C-1¦), 33.8, 32.4 (C-3, C-6), 30.1 (C-4¦), 20.8,
20.7, 20.4 (OCOCH3), 19.1, 18.4 (CH3-1, CH3-2).
Data for 9b: Rf 0.49 (1:1 hexane/AcOEt); wmax (Nujol)
3020, 2950, 2920, 2880 (CꢀH), 1735 (CꢂO ester), 1710
(CꢂO ketone) 1540, 1365 (NO2), 1215, 1055, 1040
(CꢀO) cm−1; 1H NMR (CDCl3) l 5.51 (dd, 1H,
J3%,4%=8.4 Hz, H-3%), 5.26 (dd, 1H, J2%,3%=1.2 Hz, H-
2%), 5.23 (dd, 1H, J1%,5=9.5 Hz, J1%,2%=4.0 Hz, H-1%),
5.07 (ddd, 1H, H-4%), 4.17 (dd, 1H, J4%,5%a=2.7 Hz,
J1¦,2¦a=11.4 Hz, J2¦a,2¦b=18.0 Hz, H-2¦a), 2.84 (m,
1H, H-5), 2.61 (br d, 1H, J3a,3b=18.0 Hz, H-3a), 2.60
(d, 1H, H-2¦b), 2.32 (br d, 1H, H-3b), 2.20–1.90 (m,
2H, H-6a, H-6b), 2.20, 2.16, 2.08, 2.05, 1.99, 1.95
(each s, each 3H, COCH3, 5×OCOCH3), 1.70 (s, 6H,
CH3-1, CH3-2); 13C NMR (CDCl3) l 206.2 (C-3¦),
171.1, 169.8, 169.4 (OCOCH3, COOCH3), 124.8,
122.2 (C-1, C-2), 88.4 (C-4), 69.1, 68.6, 67.8, 67.7
(C-1%, C-2%, C-3%, C-4%), 62.6 (C-5%), 52.6 (COOCH3),
45.4 (C-5), 40.5 (C-2¦), 37.5 (C-1¦), 34.6, 33.8 (C-3,
C-6), 30.2 (C-4¦), 20.9, 20.6, 20.4 (OCOCH3), 19.0,
18.3 (CH3-1, CH3-2).
J5%a,5%b=12.5 Hz, H-5%a), 4.06 (dd, 1H, J4%,5%b=5.5 Hz,
H-5%b), 3.77 (s, 3H, COOCH3), 3.41 (dd, 1H, H-1¦),
3.25 (m, 1H, J5,6a=4.6 Hz, J5,6b=1 Hz, H-5), 2.98 (br
d, 1H, J6a,6b=16.0 Hz, H-6a), 2.81 (dd, 1H, J1¦,2¦a
11.0 Hz, J2¦a,2¦b=17.7 Hz, H-2¦a), 2.47 (br d, 1H,
3a,3b=19.5 Hz, H-3a), 2.46 (dd, 1H, J1¦,2¦b=2.8 Hz,
=
J
H-2¦b), 2.25 (br d, 1H, H-3b), 2.15, 2.08, 2.05, 2.01,
1.98, 1.90 (each s, each 3H, COCH3, 5×OCOCH3),
2.01 (d, 1H, H-6b), 1.66, 1.61 (each s, each 3H, CH3-
1, CH3-2); 13C NMR (CDCl3) l 205.6 (C-3¦), 170.5,
170.1, 169.9, 169.5, 169.3 (OCOCH3, COOCH3),
122.7, 121.9 (C-1, C-2), 90.3 (C-4), 70.0, 68.8, 68.5,
66.4 (C-1%, C-2%, C-3%, C-4%), 61.7 (C-5%), 52.7
(COOCH3), 44.4 (C-5), 40.1 (C-2¦), 38.0 (C-1¦), 34.0,
33.5 (C-3, C-6), 30.0 (C-4¦), 20.7, 20.3, 20.2
(OCOCH3), 19.1, 18.4 (CH3-1, CH3-2).
3.13. 1%,2%,3%,4%,5%-Penta-O-acetyl-1%-C-[(4S,5R)-1,2-
dimethyl-4-[(1¦R)-1¦-methoxycarbonyl-3¦-oxobutyl]-4-
nitrocyclohex-1-en-5-yl]- -manno-pentitol, 8b and
D
1%,2%,3%,4%,5%-penta-O-acetyl-1%-C-[(4S,5R)-1,2-dimethyl-
4-[(1¦R)-1¦-methoxycarbonyl-3¦-oxobutyl]-4-nitrocyclo-
hex-1-en-5-yl]- -manno-pentitol, 9b
D
Following the procedure described in Section 3.2,
treatment of a solution of 1b (0.40 g, 0.78 mmol) in
acetonitrile (1.5 mL) with methyl trans-4-oxo-pen-
tenoate (0.12 g, 0.90 mmol) and TMG (0.01 mL, 0.09
mmol) at 0°C led to an oil that contained the title
compounds (ca. 1:1 ratio) together with other minor
unidentified products. Purification of this crude by
column chromatography, using 3:2 cyclohexane/
AcOEt as eluent, yielded a ca. 1:1 mixture of 8b and
9b as a colourless oil (0.40 g, 80%). CI MS m/z (rel.
3.14. 1%,2%,3%,4%,5%-Penta-O-acetyl-1%-C-[(4R,5S)-1,2-
dimethyl-4-[(1¦R)-1¦-acetyl-3¦-oxobutyl]-4-nitrocyclo-
hex-1-en-5-yl]- -galacto-pentitol, 10a and
D
1%,2%,3%,4%,5%-penta-O-acetyl-1%-C-[(4R,5S)-1,2-dimethyl-
4-[(1¦S)-1¦-acetyl-3¦-oxobutyl]-4-nitrocyclohex-1-en-5-
yl]- -galacto-pentitol, 11a
D
Following the procedure described in Section 3.2,
treatment of a solution of 1a (0.40 g, 0.78 mmol) in

R. Ballini et al. / Tetrahedron: Asymmetry 13 (2002) 1773–1787
1783
acetonitrile (1.5 mL) with cis-hex-3-en-2,5-dione (0.10
g, 0.90 mmol) and TMG (0.01 mL, 0.09 mmol) at 0°C
led to an oil that contained the title compounds (ca. 1:1
ratio) together with other minor unidentified products.
Purification of this crude by column chromatography,
using 3:2 cyclohexane/AcOEt as eluent, yielded a ca.
1:1 mixture of 10a and 11a as a colourless oil (0.36 g,
73%) CI MS m/z (rel. int.): 628 ([M+H]+, 23%), 610
(M−OH, 21), 581 (M−NO2, 30), 550 (M−OH−HOAc,
21), 521 (M−NO2−HOAc, 40), 519 (17), 504 (17), 461
(38), 407 (47), 400 (29), 341 (25), 299 (41), 281 (100); CI
HRMS: calcd for C29H41NO14+H 628.2605. Found
(M+H)+ 628.2593. Preparative thin-layer chromatogra-
phy of the mixture (1:1 hexane/AcOEt) afforded oily
samples in which each of the title compounds was
ment of a solution of 1b (0.40 g, 0.78 mmol) in acetoni-
trile (1.5 mL) with cis-hex-3-en-2,6-dione (0.10 g, 0.90
mmol) and TMG (0.01 mL, 0.09 mmol) at 0°C led to
an oil that contained the title compounds (ca. 1:1 ratio)
together with other minor unidentified products. Purifi-
cation of this crude by column chromatography, using
3:2 cyclohexane/AcOEt as eluent, yielded a ca. 1:1
mixture of 10b and 11b as a colourless oil (0.37 g, 75%).
CI MS m/z (rel. int.): 628 ([M+H]+, 22%), 610 (M−OH,
32), 581 (M−NO2, 37), 550 (M−OH−HOAc, 15), 521
(M−NO2−HOAc, 40), 519 (52), 504 (27), 459 (35), 407
(77), 400 (42), 341 (26), 299 (76), 281 (100); HRMS (CI)
calcd for C29H41NO14+H 628.2605. Found (M+H)+
628.2569. Preparative thin-layer chromatography of the
mixture (1:1 hexane/AcOEt) afforded oily samples in
which each of the title compounds was clearly predom-
inant. Data for 10b: Rf 0.47 (1:1 hexane/AcOEt); wmax
(Nujol) 3010, 2980, 2960 (CꢀH), 1745 (CꢂO ester), 1715
1
clearly predominant. Data for 10a: H NMR (CDCl3) l
5.28 (ddd, 1H, H-4%), 5.27 (d, 1H, J2%,3%=9.7 Hz, H-2%),
5.00 (d, 1H, J1%,5=10.5 Hz, H-1%), 4.93 (dd, 1H, J3%,4%
=
2.3 Hz, H-3%), 4.32 (dd, 1H, J4%,5%a=3.9 Hz, J5%a,5%b=12.0
Hz, H-5%a), 3.77 (dd, 1H, J4%,5%b=7.9 Hz, H-5%b), 3.50 (d,
1H, H-1¦), 2.91 (dd, 1H, J1¦,2¦a=11.7 Hz, J2¦a,2¦b=18.5
Hz, H-2¦a), 2.89 (dd, 1H, J5,6a=4.7 Hz, J5,6b=1 Hz,
H-5), 2.55 (dd, 1H, J1¦,2¦b=2.2 Hz, H-2¦b), 2.40 (br d,
1H, J3a,3b=19.0 Hz, H-3a), 2.35 (br d, 1H, H-3b), 2.25,
2.18, 2.11, 2.09, 2.07, 2.00, 1.97 (each s, each 3H,
2×COCH3 and 5×OCOCH3), 2.20–1.90 (m, 2H, H-6a,
H-6b), 1.72 and 1.70 (each s, each 3H, CH3-1, CH3-2);
13C NMR (CDCl3) l 206.6, 206.1 (C-3¦, CHCOCH3),
170.8, 170.5, 170.3, 170.2, 169.7 (OCOCH3), 124.0,
122.3 (C-1, C-2), 90.5 (C-4), 69.0, 68.8, 68.7, 68.4 (C-1%,
C-2%, C-3%, C-4%), 62.8 (C-5%), 49.0 (C-5), 41.7 (C-2¦),
37.9 (C-1¦), 34.0, 33.6 (C-3, C-6), 33.2 (CHCOCH3),
29.8 (CH2COCH3), 20.8, 20.6, 20.2 (OCOCH3), 19.0,
18.6 (CH3-1, CH3-2). Data for 11a: Rf 0.42 (1:1 hexane/
AcOEt); wmax (Nujol) 3010, 2980, 2920 (CꢀH), 1740
(CꢂO ketone), 1545, 1370 (NO2), 1230, 1060, 1040
1
(CꢀO) cm−1; H NMR (CDCl3) l 5.52 (dd, 1H, J3%,4%
=
8.2 Hz, H-3%), 5.21 (dd, 1H, J2%,3%=1.7 Hz, H-2%), 5.20
(dd, 1H, J1%,5=9.8 Hz, J1%,2%=3.7 Hz, H-1%), 5.09 (ddd,
1H, H-4%), 4.22 (dd, 1H, J4%,5%a=2.7 Hz, J5%a,5%b=12.5 Hz,
H-5%a), 4.07 (dd, 1H, J4%,5%b=5.9 Hz, H-5%b), 3.58 (dd,
1H, H-1¦), 3.17 (dd, 1H, J1¦,2¦a=11.1 Hz, J2¦a,2¦b=17.7
Hz, H-2¦a), 3.01 (dd, 1H, J5,6a=5.8 Hz, J5,6b=1 Hz,
H-5), 2.96 (dd, 1H, J1¦,2¦b=1.9 Hz, H-2¦b), 2.48 (br d,
1H, J3a,3b=18.1 Hz, H-3a), 2.25 (br d, 1H, H-3b), 2.18,
2.16, 2.15, 2.05, 2.04, 1.99, 1.95 (each s, each 3H,
2×COCH3, 5×OCOCH3), 2.20–1.90 (m, 2H, H-6a, H-
6b), 1.73 (s, 6H, CH3-1, CH3-2); 13C NMR (CDCl3) l
207.9, 207.5 (COCH3), 170.4, 170.2, 169.9, 169.6
(OCOCH3), 123.5, 122.0 (C-1, C-2), 88.0 (C-4), 68.8,
68.7, 66.6 (C-1%, C-2%, C-3%, C-4%), 61.8 (C-5%), 47.8 (C-5),
42.0 (C-2¦), 37.2 (C-1¦), 34.3 (C-3), 33.1, 29.8
(COCH3), 32.6 (C-6), 20.7, 20.6, 20.3, 20.0 (OCOCH3),
19.1, 18.5 (CH3-1, CH3-2). Data for 11b: Rf 0.42 (1:1
hexane/AcOEt); wmax (Nujol) 3010, 2980, 2950 (CꢀH),
1745 (CꢂO ester), 1715 (CꢂO ketone), 1540, 1365
(NO2), 1220, 1050, 1020 (CꢀO) cm−1; 1H NMR (CDCl3)
l 3.60 (dd, 1H, H-1¦), 3.18 (dd, 1H, J5,6a=5.8 Hz,
1
(CꢂO), 1540, 1360 (NO2), 1210, 1030 (CꢀO) cm−1; H
NMR (CDCl3) l 5.28 (ddd, 1H, H-4%), 5.19 (d, 1H,
J2%,3%=9.9 Hz, H-2%), 4.97 (d, 1H, J1%,5=10.9 Hz, H-1%),
4.94 (dd, 1H, J3%,4%=2.1 Hz, H-3%), 4.33 (dd, 1H, J4%,5%a
3.9 Hz, J5%a,5%b=12.0 Hz, H-5%a), 3.77 (dd, 1H, J4%,5%b
=
=
7.9 Hz, H-5%b), 3.55 (d, 1H, H-1¦), 3.14 (dd, 1H,
J
1¦,2¦a=11.5 Hz, J2¦a,2¦b=18.7 Hz, H-2¦a), 2.78 (dd, 1H,
J5,6a=4.9 Hz, J5,6b=1 Hz, H-5), 2.69 (dd, 1H, J1¦,2¦b
=
J
5,6b=1 Hz, H-5), 3.00 (dd, 1H, J2¦a,2¦b=18.2 Hz, H-
2.0 Hz, H-2¦b), 2.45 (br d, 1H, J3a,3b=19.5 Hz, H-3a),
2.29 (br d, 1H, H-3b), 2.23, 2.19, 2.13, 2.08, 2.07, 1.99,
1.95 (each s, each 3H, 2×COCH3 and 5×OCOCH3),
2.15 (m, 1H, H-6a), 2.08 (m, 1H, H-6b), 1.75 and 1.74
(each s, each 3H, CH3-1, CH3-2); 13C NMR (CDCl3) l
207.3, 206.7 (C-3¦, CHCOCH3), 170.9, 170.5, 170.4,
170.2, 169.6 (OCOCH3), 123.8, 122.2 (C-1, C-2), 88.0
(C-4), 68.7, 68.5, 68.2, 68.1 (C-1%, C-2%, C-3%, C-4%), 62.8
(C-5%), 48.3 (C-5), 42.0 (C-2¦), 37.6 (C-1¦), 34.4, 33.1
(C-3, C-6), 33.3 (CHCOCH3), 29.8 (CH2COCH3), 20.7,
20.6, 20.1 (OCOCH3), 19.0, 18.5 (CH3-1, CH3-2).
2¦a), 2.96 (dd, 1H, J1¦,2¦b=1.9 Hz, H-2¦b); 13C NMR
(CDCl3) l 90.2 (C-4), 72.0 (C-1%), 91.9 (C-5%), 50.5
(C-5), 42.5 (C-2¦), 37.5 (C-1¦).
3.16. 1%,2%,3%,4%,5%-Penta-O-acetyl-1%-C-[(5S)-1,2-
dimethyl-4-[(1¦R)-1¦,2¦-dimethoxycarbonylethyl]-
cyclohex-1,3-dien-5-yl]- -galacto-pentitol, 12a and
D
1%,2%,3%,4%,5%-penta-O-acetyl-1%-C-[(5S)-1,2-dimethyl-4-
[(1¦S)-1¦,2¦-dimethoxycarbonylethyl]cyclohex-1,3-dien-5-
yl]- -galacto-pentitol, 13a
D
Following the procedure described in Section 3.2, treat-
ment of a solution of 1a (0.50 g, 0.97 mmol) in acetoni-
trile (2.0 mL) with either dimethyl fumarate or dimethyl
maleate (0.29 mL, 1.94 mmol) and DBU (0.29 mL, 1.94
mmol) led to an oil that contained the title compounds
(ca. 1:1 ratio) together with other minor unidentified
products. Purification of this crude by column chro-
matography, using 3:2 cyclohexane/AcOEt as eluent,
3.15. 1%,2%,3%,4%,5%-Penta-O-acetyl-1%-C-[(4S,5R)-1,2-
dimethyl-4-[(1¦R)-1¦-acetyl-3¦-oxobutyl]-4-nitrocyclo-
hex-1-en-5-yl]- -manno-pentitol, 10b and
D
1%,2%,3%,4%,5%-penta-O-acetyl-1%-C-[(4S,5R)-1,2-dimethyl-
4-[(1¦S)-1¦-acetyl-3¦-oxobutyl]-4-nitrocyclohex-1-en-5-
yl]- -manno-pentitol, 11b
D
Following the procedure described in Section 3.2, treat-

1784
R. Ballini et al. / Tetrahedron: Asymmetry 13 (2002) 1773–1787
yielded a ca. 1:1 mixture of 12a and 13a as a colourless
oil (0.60 g, quantitative). CI MS m/z (rel. int.): 613
([M+H]+, 30%), 551 (M−NO2−CH3, 66), 493 (M−NO2−
CH3−C3H6O, 12), 433 (25), 373 (34), 213 (22); CI
HRMS calcd for C29H40O14+H 613.2496. Found (M+
H)+ 613.2478. Preparative thin-layer chromatography
of the mixture (1:1 hexane/AcOEt) afforded oily sam-
ples in which each of the title compounds was clearly
predominant. Data for 12a: Rf 0.42 (1:1 hexane/
AcOEt); wmax (Nujol) 2940, 2920 (CꢀH), 1740 (CꢂO),
oil that contained the title compounds (ca. 1:1 ratio)
together with other minor unidentified products. Purifi-
cation of this crude by column chromatography, using
3:2 cyclohexane/AcOEt as eluent, yielded a ca. 1:1
mixture of 12b and 13b as a colourless oil (0.36 g, 78%).
Preparative thin-layer chromatography of the mixture
(1:1 hexane/AcOEt) afforded oily samples in which
each of the title compounds was clearly predominant.
1
Data for 12b: Rf 0.47 (1:1 hexane/AcOEt); H NMR
(CDCl3) l 5.64 (s, 1H, H-3), 5.49 (dd, 1H, J3%,4%=9.9
Hz, H-3%), 5.29 (dd, 1H, J2%,3%=2.0 Hz, H-2%), 5.20 (dd,
1H, J1%,5=8.7 Hz, J1%,2%=3.8 Hz, H-1%), 5.05 (m, 1H,
H-4%), 4.22 (dd, 1H, J4%,5%a=2.9 Hz, J5%a,5%b=12.2 Hz,
H-5%a), 4.12 (dd, 1H, J4%,5%b=5.5 Hz, H-5%b), 3.70 (dd,
1H, H-1¦), 3.66 (s, 3H, COOCH3), 3.08 (dd, 1H,
1
1210, 1040 (CꢀO) cm−1; H NMR (CDCl3) l 5.57 (s,
1H, H-3), 5.39 (d, 1H, J1%,5=10.0 Hz, H-1%), 5.29 (m,
1H, H-4%), 5.23 (d, 1H, J2%,3%=9.8 Hz, H-2%), 5.09 (dd,
1H, J3%,4%=2.0 Hz, H-3%), 4.31 (dd, 1H, J4%,5%a=4.1 Hz,
J
5%a,5%b=11.6 Hz, H-5%a), 3.81 (dd, 1H, J4%,5%b=7.6 Hz,
H-5%b), 3.71 and 3.68 (each s, each 3H, COOCH3), 3.50
(dd, 1H, H-1¦), 2.84 (dd, 1H, J1¦,2¦a=10.7 Hz, J2¦a,2¦b
J
J
1¦,2¦a=11.7 Hz, J2¦a,2¦b=16.0 Hz, H-2¦a), 2.35 (dd, 1H,
1¦,2¦b=4.5 Hz, H-2¦b), 2.20–1.90 (m, 3H, H-5, H-6a,
=
16.9 Hz, H-2¦a), 2.47 (dd, 1H, J1¦,2¦b=4.0 Hz, H-2¦b),
2.29 (m, 1H, J6a,6b=17.9 Hz, H-6a), 2.18, 2.10, 2.09,
2.08, 2.02 (each s, each 3H, 5×OCOCH3), 2.10 (m, 1H,
H-6b), 2.08 (m, 1H, H-5), 1.80, 1.68 (each s, each 3H,
CH3-1, CH3-2); 13C NMR (CDCl3) l 172.8, 172.3,
170.2, 169.9 (COOCH3, OCOCH3), 131.6, 125.3, 125.0
(C-1, C-2, C-4), 128.5 (C-3), 68.1, 68.7 (C-1%, C-2%, C-3%,
C-4%), 62.7 (C-5%), 52.0, 51.9 (COOCH3), 47.4 (C-5),
37.2, 33.1 (C-3, C-6), 35.2 (C-1¦), 20.7, 20.6, 20.5
(OCOCH3), 19.2, 16.7 (CH3-1, CH3-2). Data for 13a:
Rf 0.48 (1:1 hexane/AcOEt); wmax (Nujol) 2940, 2920
H-6b), 2.12, 2.08, 2.05, 2.02, 1.97 (each s, each 3H,
COCH3 and 5×OCOCH3), 1.76, 1.64 (each s, each 3H,
CH3-1, CH3-2). Data for 13b: Rf 0.45 (1:1 hexane/
1
AcOEt); H NMR (CDCl3) l 5.66 (s, 1H, H-3), 5.49
(dd, 1H, J3%,4%=9.8 Hz, H-3%), 5.29 (dd, 1H, J2%,3%=1.9
Hz, H-2%), 5.21 (dd, 1H, J1%,5=9.7 Hz, J1%,2%=4.0 Hz,
H-1%), 5.03 (m, 1H, H-4%), 4.21 (dd, 1H, J4%,5%a=2.8 Hz,
J
5%a,5%b=12.6 Hz, H-5%a), 4.08 (dd, 1H, J4%,5%b=5.6 Hz,
H-5%b), 3.69 (dd, 1H, H-1¦), 3.68 (s, 3H, COOCH3),
3.28 (dd, 1H, J1¦,2¦a=11.9 Hz, J2¦a,2¦b=15.4 Hz, H-2¦a),
2.49 (m, 1H, H-5), 2.45 (dd, 1H, J1¦,2¦b=4.5 Hz, H-2¦b),
2.20–1.90 (m, 2H, H-6a, H-6b), 2.18, 2.14, 2.11, 2.06,
2.03, 1.94 (each s, each 3H, COCH3, 5×OCOCH3),
1.78, 1.68 (each s, each 3H, CH3-1, CH3-2).
1
(CꢀH), 1740 (CꢂO), 1210, 1040 (CꢀO) cm−1; H NMR
(CDCl3) l 5.64 (s, 1H, H-3), 5.30 (d, 1H, J1%,5=10.7 Hz,
H-1%), 5.27 (d, 1H, H-2%), 5.25 (d, 1H, H-4%), 5.12 (dd,
1H, J2%,3%=9.7 Hz, J3%,4%=1.7 Hz, H-3%), 4.30 (dd, 1H,
J
J
4%,5%a=4.4 Hz, J5%a,5%b=11.6 Hz, H-5%a), 3.82 (dd, 1H,
4%,5%b=7.5 Hz, H-5%b), 3.69 (s, 6H, CH2COOCH3,
The same result was achieved when a ca. 1:1 mixture of
8b and 9b was treated with DBU (2.0 equiv.) for 24 h
at room temperature.
CHCOOCH3), 3.50 (dd, 1H, H-1¦), 3.10 (dd, 1H,
J
J
1¦,2¦a=11.8 Hz, J2¦a,2¦b=16.7 Hz, H-2¦a), 2.42 (dd, 1H,
5,6a=6.0 Hz, H-5), 2.36 (dd, 1H, J1¦,2¦b=3.1 Hz, H-
2¦b), 2.33 (m, 1H, H-6a), 2.18, 2.11, 2.07, 2.04, 1.99
(each s, each 3H, 5×OCOCH3), 2.08 (m, 1H, H-6b),
1.79, 1.70 (each s, each 3H, CH3-1, CH3-2); 13C NMR
(CDCl3) l 172.9, 172.2 170.5, 170.3, 170.1 (COOCH3,
OCOCH3), 130.8, 125.8, 124.8 (C-1, C-2, C-4), 128.1
(C-3), 68.3, 68.0, 67.9, 67.8 (C-1%, C-2%, C-3%, C-4%), 62.5
(C-5%), 52.3, 51.9 (COOCH3), 46.7 (C-5), 35.1 (C-1¦),
34.7, 33.1 (C-3, C-6), 32.7 (C-2¦), 20.7, 20.6, 20.5
(OCOCH3), 19.2, 16.7 (CH3-1, CH3-2).
3.18. 1%-C-[(4R,5S)-1,2-Dimethyl-4-(2¦-methoxycar-
bonylethyl)-4-nitrocyclohex-1-en-5-yl]-
D
-galacto-pentitol,
2c
A solution of 2a (2.05 g, 3.41 mmol) in methanol (25
mL) was treated with a catalytic amount of 2 M sodium
methoxide in methanol. After stirring for 12 h at room
temperature, there was apparition of a white solid,
which was filtered and recrystallized from methanol/
water (1.24 g, 93%): mp 178–180°C; Rf 0.35 (AcOEt);
[h]D=+9.4 (c 0.64, MeOH); wmax (KBr) 3460, 3320
(OH), 2980, 2940, 2900, 2850 (CH), 1730 (CꢂO), 1530,
The same result was achieved when a ca. 1:1 mixture of
6a and 7a was treated with DBU (2.0 equiv.) for 24 h
at room temperature.
1
1330 (NO2), 1220, 1090, 1030 (CꢀO) cm−1; H NMR
(DMSO-d6) l 4.43 (t, 1H, JH,OH-5%=5.7 Hz, OH-5%),
4.23 (d, 2H, 2×OH), 4.06 (d, 1H, JH,OH=7.0 Hz, OH),
3.85 (d, 1H, J1%,OH=8.5 Hz, OH-1%), 3.69 (m, 1H,
3.17. 1%,2%,3%,4%,5%-Penta-O-acetyl-1%-C-[(5R)-1,2-
dimethyl-4-[(1¦R)-1¦-methoxycarbonyl-3¦-oxobutyl]-
J4%,5%a=J4%,5%b=6.5 Hz, H-4%), 3.64 (dd, 1H, J1%,5=10.2
cyclohex-1,3-dien-5-yl]- -manno-pentitol, 12b and
D
Hz, H-1%), 3.58 (s, 3H, COOCH3), 3.40–3.25 (m, 4H,
H-2%, H-3%, H-5%a, H-5%b), 2.83 (br d, 1H, J3a,3b=17.0
Hz, H-3a), 2.73 (dd, 1H, J5,6a=4.7 Hz, J5,6b=1 Hz,
H-5), 2.10–2.00 (m, 3H, H-1¦a, H-1¦b, H-2¦b), 2.33 (m,
1H, H-2¦a), 2.25 (d, 1H, H-3b), 2.22 (br d, 1H, H-6a),
1.85 (d, 1H, J6a,6b=18.3 Hz, H-6b), 1.66, 1.58 (each s,
each 3H, CH3-1, CH3-2); 13C NMR (DMSO-d6) l 173.6
(C-3¦), 124.4, 123.4 (C-1, C-2), 90.0 (C-4), 70.7, 70.4,
1%,2%,3%,4%,5%-penta-O-acetyl-1%-C-[(5R)-1,2-dimethyl-4-
[(1¦S)-1¦-methoxycarbonyl-3¦-oxobutyl]cyclohex-1,3-
dien-5-yl]- -manno-pentitol, 13b
D
Following the procedure described in Section 3.2, treat-
ment of a solution of 1b (0.40 g, 0.78 mmol) in acetoni-
trile (1.5 mL) with methyl trans-4-oxo-pentenoate (0.12
g, 0.90 mmol) and DBU (0.23 mL, 1.56 mmol) led to an

R. Ballini et al. / Tetrahedron: Asymmetry 13 (2002) 1773–1787
1785
(m, 1H, H-3b), 2.06 (s, 3H, COCH3), 2.05 (br d, 1H,
69.6, 69.5 (C-1%, C-2%, C-3%, C-4%), 63.8 (C-5%), 52.6
(C-4¦), 41.8 (C-5), 34.9, 33.4, 33.3 (C-3, C-6, C-1¦), 28.6
(C-2¦), 19.9, 19.1 (CH3-1, CH3-2). Anal. calcd for
C17H29NO9.1/2 H2O: C, 50.99; H, 7.55; N, 3.49. Found:
C, 50.66; H, 7.44; N, 3.44%. Surface tension: kl=50
mN/m (20°C, 10−3 mol/L, in aqueous solution).
J6a,6b=18.5 Hz, H-6b), 1.85 (m, 2H, H-1¦a, H-1¦b),
1.65, 1.57 (each s, each 3H, CH3-1, CH3-2); 13C NMR
(DMSO-d6) l 209.6 (C-3¦), 123.9, 122.7 (C-1, C-2), 89.6
(C-4), 73.4, 72.0, 71.7, 70.6 (C-1%, C-2%, C-3%, C-4%), 64.1
(C-5%), 42.5 (C-5), 37.3, 35.7, 35.0, 32.3 (C-1¦, C-2¦, C-3,
C-6), 30.7 (C-4¦), 19.1, 19.9 (CH3-1, CH3-2). Anal.
calcd for C17H29NO8: C, 54.39; H, 7.79; N, 3.73.
Found: C, 54.58; H, 7.64; N, 3.52%.
3.19. 1%-C-[(4S,5R)-1,2-Dimethyl-4-(2¦-methoxycar-
bonylethyl)-4-nitrocyclohex-1-en-5-yl]-
2d
D
-manno-pentitol,
3.21. 1%-C-[(4S,5R)-4-(2¦-Cyanoethyl)-1,2-dimethyl-4-
A solution of 2b (0.96 g, 1.60 mmol) in methanol (5 mL)
was treated with a catalytic amount of 2 M sodium
methoxide in methanol. After stirring for 24 h at room
temperature, the reaction mixture was neutralized with
Amberlite IR-120 (H+) and the solvent was evaporated,
yielding the title compound as an oil, which crystallized
from methanol (0.43 g, 69%) and was recrystallized from
chloroform: mp 123−125°C; Rf 0.40 (AcOEt); [h]D=+
65.2 (c 0.52, CHCl3); wmax (KBr) 3500, 3440, 3280 (OH),
3000, 2965, 2940, 2920, 2890, 2840 (CH), 1740 (CꢂO),
1535, 1340 (NO2), 1270, 1060, 1020 (CꢀO) cm−1; 1H NMR
(DMSO-d6) l 4.99 (d, 1H, J1%,OH=6.6 Hz, OH-1%), 4.48
(d, 1H, JH,OH=6.8 Hz, OH), 4.44 (d, 1H, JH,OH=5.7 Hz,
OH), 4.36 (t, 1H, JH,OH-5%=5.5 Hz, OH-5%), 4.11 (d, 1H,
nitrocyclohex-1-en-5-yl]- -manno-pentitol, 4d
D
Following the procedure described in Section 3.18,
treatment of a solution of 4b (1.00 g, 1.76 mmol) in
methanol (15 mL) with a catalytic amount of 2 M
sodium methoxide for 1.5 h led to a solid, which was
recrystallized from methanol (0.49 g, 78%): mp 168–
170°C, Rf 0.44 (AcOEt); [h]D=+13.1 (c 0.49, MeOH);
wmax (film) 3400, 3360 (OH), 2920, 2880 (CꢀH), 1535,
1340 (NO2), 1070, 1035 (CꢀO) cm−1; 1H NMR (DMSO-
d6) l 5.06 (d, 1H, J1%,OH=6.5 Hz, OH-1%), 4.60–4.10 (m,
4H, 4×OH), 3.70–3.30 (m, 6H, H-1%, H-2%, H-3%, H-4%,
H-5%a, H-5%b), 2.92 (br d, 1H, J3a,3b=17.7 Hz, H-3a),
2.71 (t, 1H, J1%,5=J5,6a 5.9 Hz, H-5), 2.50–2.00 (m, 4H,
H-1¦a, H-1¦b, H-2¦a, H-2¦b), 2.33 (d, 1H, H-3b), 2.22
(br d, 1H, H-6a), 2.02 (d, 1H, H-6b), 1.67, 1.58 (each s,
each 3H, CH3-1, CH3-2); 13C NMR (DMSO-d6) l
122.9, 122.4 (C-1, C-2), 120.1 (C-3¦), 88.4 (C-4), 72.4,
72.0, 71.5, 70.2 (C-1%, C-2%, C-3%, C-4%), 63.9 (C-5%), 42.3
(C-5), 34.6, 33.3 (C-1¦, C-3, C-6), 19.3, 18.6 (CH3-1,
CH3-2), 11.5 (C-2¦). Anal. calcd for C16H26N2O7: C,
53.62; H, 7.31; N, 7.82. Found: C, 53.43; H, 7.38; N,
7.69%.
JH,OH=6.8 Hz, OH), 3.56 (s, 3H, COOCH3), 3.60–3.50
(m, 3H, H-2%, H-3%, H-5%a), 3.37 (m, 2H, H-1%, H-5%b), 2.92
(br d, 1H, J3a,3b=17.0 Hz, H-3a), 2.71 (t, 1H, J1%,5=J5,6a
5.5 Hz, H-5), 2.30 (dt, 1H, J2¦a,2¦b=16.5 Hz, J1¦a,2¦a
=
=
J1¦b,2¦a=7.9 Hz, H-2¦a), 2.21 (br d, 1H, H-3b), 2.18 (m,
1H, H-6a), 2.09 (m, 1H, H-2¦b), 2.07 (d, 1H, J6a,6b=16.5
Hz, H-6b), 1.95 (t, 2H, J1¦,2¦=7.9 Hz, H-1¦a, H-1¦b), 1.65,
1.57 (each s, each 3H, CH3-1, CH3-2); 13C NMR (DMSO-
d6) l 173.1 (C-3¦), 123.6, 122.4 (C-1, C-2), 89.3 (C-4), 72.6
(C-1%), 72.2 (C-2%), 71.6 (C-3%), 70.4 (C-4%), 64.0 (C-5%), 52.3
(C-4¦), 42.3 (C-5), 35.5 (C-3), 34.9 (C-6), 33.3 (C-2¦), 28.3
(C-1¦), 19.7, 19.0 (CH3-1, CH3-2). Anal. calcd for
C17H29NO9: C, 52.17; H, 7.47; N, 3.58. Found: C, 52.04;
H, 7.28; N, 3.53%. Surface tension: kl=68 mN/m (20°C,
10−3 mol/L, in aqueous solution.
3.22. (4R,5S)-5-Formyl-1,2-dimethyl-4-(2¦-methoxycar-
bonylethyl)-4-nitrocyclohex-1-ene, 2e and its (2,4-dinitro-
phenylhydrazone), 2g
To a stirred solution of 3c (0.50 g, 1.28 mmol) in water
(78 mL) was added a solution of sodium metaperiodate
(1.37 g, 6.42 mmol) in water (2 mL). After stirring for
15 min at 0°C, the solution was extracted with methyl-
ene chloride (4×50 mL) and washed with water (2×30
mL). The organic layer was dried over MgSO4 and the
solvent evaporated, yielding the title compound as a
colourless oil (0.34 g, 100%): Rf 0.54 (3:1 hexane/
AcOEt); [h]D=−2.6 (c 0.52, CHCl3); wmax (film) 2980,
2940, 2900, 2850 (CꢀH), 2720 (CHO), 1720 (CꢂO),
3.20. 1%-C-[(4S,5R)-1,2-Dimethyl-4-nitro-4-(3¦-
oxobutyl)-cyclohex-1-en-5-yl]- -manno-pentitol, 3d
D
Following the procedure described in Section 3.18,
treatment of a solution of 3b (2.00 g, 3.42 mmol) in
methanol (30 mL) with a catalytic amount of 2 M sodium
methoxide for 1.5 h, led to a solid, which was crystallized
from methanol (0.68 g, 53%): mp 119–121°C, Rf 0.40
(AcOEt); [h]D=+5.8 (c 0.52, H2O); wmax (KBr) 3510, 3280
(OH), 2920, 2850 (CꢀH), 1710 (CꢂO), 1530, 1350 (NO2),
1260, 1070, 1045 (CꢀO) cm−1; 1H NMR (DMSO-d6) l 4.96
(d, 1H, J1%,OH=6.6 Hz, OH-1%), 4.46 (d, 1H, JH,OH=5.9
Hz, OH), 4.44 (d, 1H, JH,OH=4.9 Hz, OH), 4.36 (t, 1H,
1
1530, 1340 (NO2), 1190, 1170 (CꢀO) cm−1; H NMR
(CDCl3) l 9.60 (s, 1H, H-1%), 3.66 (s, 3H, COOCH3),
3.14 (t, 1H, J5,6a=J5,6b=5.7 Hz, H-5), 2.92 (d, 1H,
J
3a,3b=17.6 Hz, H-3a), 2.45–2.20 (m, 7H, H-1¦a, H-1¦b,
H-2¦a, H-2¦b, H-3b, H-6a, H-6b), 1.64, 1.63 (each s,
each 3H, CH3-1, CH3-2); 13C NMR (CDCl3) l 199.2
(C-1%), 172.1 (C-3¦), 123.3, 122.4 (C-1, C-2), 88.6 (C-4),
51.9 (C-5), 50.5 (C-4¦), 36.9 (C-3), 32.6 (C-6), 29.9
(C-2¦), 27.9 (C-1¦), 18.9, 18.2 (CH3-1, CH3-2).
JH,OH=5.5 Hz, OH-5%), 4.12 (d, 1H, JH,OH=6.6 Hz, OH),
3.60–3.30 (m, 4H, H-2%, H-3%, H-5%a, H-5%b), 3.45 (m, 1H,
J4%,5%a=2.3 Hz, H-4%), 3.36 (m, 1H, H-1%), 2.91 (br d, 1H,
J3a,3b=16.6 Hz, H-3a), 2.70 (m, 1H, J1%,5=8.9 Hz,
J5,6a=5.2Hz, J5,6b=1Hz, H-5), 2.44(m, 1H, J2¦a,2¦b=18.4
Hz, J1¦a,2¦a=J1¦b,2¦a=7.6 Hz, H-2¦a), 2.23 (m, 1H,
Treatment of a solution of aldehyde 2e (0.16 g, 0.60
mmol) in methanol (14 mL) with (2,4-dinitro-
J
1¦a,2¦b=J1¦b,2¦b=7.6 Hz, H-2¦b), 2.21 (m, 1H, H-6a), 2.18

1786
R. Ballini et al. / Tetrahedron: Asymmetry 13 (2002) 1773–1787
phenyl)hydrazine (0.20 g, 0.99 mmol) yielded its crys-
talline (2,4-dinitro-phenyl)hydrazone 2g (0.09 g, 35%):
mp 121–123°C (from benzene/MeOH); Rf 0.65 (2:1
hexane/AcOEt); [h]D=+10.6 (c 0.53, CHCl3); wmax
(KBr) 3270 (NH), 2950, 2920, 2840 (CH), 1730 (CꢂO),
1610, 1580 (CHꢂN, CꢂC), 1530, 1330 (NO2), 1130
(br d, 1H, J3a,3b=17.6 Hz, H-3a), 2.53–2.17 (m, 7H,
H-1¦a, H-1¦b, H-2¦a, H-2¦b, H-3b, H-6a, H-6b), 1.67
(s, 6H, CH3-1, CH3-2); 13C NMR (CDCl3) l 199.3
(CHO), 123.6, 122.9 (C-1, C-2), 118.4 (C-3¦), 88.5
(C-4), 50.4 (C-5), 36.8, 33.4, 30.3 (C-3, C-6, C-1¦), 19.3,
18.6 (CH3-1, CH3-2), 12.2 (C-2¦). CI MS m/z (rel. int.):
236 (M+H, 4%), 188 (M−H2O−NO, 100), 172 (M−
H2O−NO2, 44), 159 (21), 145 (32), 119 (74); CI HRMS:
calcd for C12H16N2O3+H 236.1160. Found (M+H)+
236.1117.
1
(CꢀO) cm−1; H NMR (CDCl3) l 11.08 (s, 1H, NH),
9.11 (d, 1H, H-3Ar), 8.32 (dd, 1H, J5Ar,6Ar=9.7 Hz,
J5Ar,3Ar=2.8 Hz, H-5Ar), 7.79 (d, 1H, H-6Ar), 7.54 (d,
1H, J5,CHꢂN=5.8 Hz, CHꢂN), 3.68 (s, 3H, COOCH3),
6
3.29 (dd, 1H, J5,6a=6.0 Hz, J5,6b=12.0 Hz, H-5), 2.93
(br d, 1H, J3a,3b=17.8 Hz, H-3a), 2.50–2.20 (m, 7H,
H-3b, H-6a, H-6b, H-1¦a, H-1¦b, H-2¦a, H-2¦b), 1.70,
1.68 (each s, each 3H, CH3-1, CH3-2); 13C NMR
(CDCl3) l 172.2 (C-3¦), 149.5 (CHꢂN), 144.8 (C-1Ar),
138.3 (C-4Ar), 130.1, 129.3 (C-5Ar, C-2Ar), 123.3 (C-
3Ar), 123.0, 122.8 (C-1, C-2), 116.5 (C-6Ar), 90.5 (C-4),
52.0 (C-4¦), 44.1 (C-5), 36.6, 33.4, 32.8, 28.1 (C-3, C-6,
C-1¦, C-2¦), 19.0, 18.4 (CH3-1, CH3-2). Anal. calcd for
C19H23N5O8: C, 50.78; H, 5.16; N, 15.58. Found: C,
50.54; H, 5.11; N, 16.02%.
Acknowledgements
This work was supported by the Spanish Ministerio de
Educacio´n y Cultura (CICYT, PB98-0997), the Junta
de Extremadura-Fondo Social Europeo through grant
IPR00C021 and by the MIUR, Italy in the framework
of the National Project ‘Stereoselezione in Sintesi
Organica: Metodologie ed Applicazioni’. We also thank
the Unidad de Espectrometr´ıa de Masas de la Universi-
dad de Co´rdoba and the Universidad de Extremadura
(Programa Propio) for a postdoctoral fellowship to M.
V. Gil.
3.23. (4S,5R)-5-Formyl-1,2-dimethyl-4-(2-methoxycar-
bonylethyl)-4-nitrocyclohex-1-ene, 2f
Following the same procedure described above for the
preparation of its enantiomer 2e, oxidation of 2d (0.12
g, 0.31 mmol) led to the title compound as a colourless
oil (56 mg, 68%): Rf 0.58 (3:1 hexane/AcOEt); [h]D=
+2.5 (c 0.5, CHCl3). IR, 1H and 13C NMR data
matched those for 2e.
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(NO2) cm−1; H NMR (CDCl3) l 9.61 (s, 1H, CHO),
3.16 (t, 1H, J5,6a=J5,6b=5.4 Hz, H-5), 2.93 (br d, 1H,
J
J
3a,3b=17.7 Hz, H-3a), 2.55 (m, 1H, J2¦a,2¦b=17.5 Hz,
1¦a,2¦a=10.1 Hz, J1¦b,2¦a=3.0 Hz, H-2¦a), 2.45 (m, 2H,
H-6a, H-6b), 2.40 (m, 1H, H-2¦b), 2.34 (br d, 1H,
H-3b), 2.3–2.1 (m, 2H, H-1¦a, H-1¦b), 2.16 (s, 3s,
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4-nitrocyclohex-1-ene, 4f
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(0.35 g, 0.96 mmol) led to the title compound as a
colourless oil (0.16 g, 69%): Rf 0.42 (3:1 hexane/
AcOEt); [h]D=+16.5 (c 0.54, CHCl3); wmax (film) 2910,
2850 (C–H), 2720 (CHO), 2240 (CN), 1715 (CꢂO),
1
1535, 1350 (NO2) cm−1; H NMR (CDCl3) l 9.56 (s,
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