An efficient and highly diastereoselective synthesis of C-glycosylated 1,3-oxazolidines from N-methyl-d-glucamine

Article abstract of DOI:10.1016/j.tet.2008.04.082

A one-pot procedure for preparing chiral 1,3-oxazolidines derived from N-methyl-d-glucamine and aryl aldehydes is described. It has been carried out by using readily available reagents and operationally simple conditions allowing the preparation of the acyclic C-nucleoside analogs in high yields. The structure of these derivatives has been fully characterized by NMR correlations and single-crystal X-ray diffraction. Some reactions also provide access to the corresponding tetrahydro-1,3-oxazines by an alternative ring closure. Mechanistic considerations account for the observed steric course. Crown Copyright

Full text of DOI:10.1016/j.tet.2008.04.082

Tetrahedron 64 (2008) 6377–6386
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
An efficient and highly diastereoselective synthesis of C-glycosylated
1,3-oxazolidines from N-methyl-D-glucamine
a
,
a
a
a
a
b
*
´
´
´
´
´
R. Fernando Martınez , Martın Avalos , Reyes Babiano , Pedro Cintas , Jose L. Jimenez , Mark E. Light ,
a
a
´
Juan C. Palacios , Esther M.S. Perez
a
´
´
´
Departamento de Quımica Organica e Inorganica, QUOREX Research Group, Universidad de Extremadura, E-06071 Badajoz, Spain
b Department of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
A one-pot procedure for preparing chiral 1,3-oxazolidines derived from N-methyl-D-glucamine and aryl
Received 13 March 2008
Received in revised form 10 April 2008
Accepted 22 April 2008
aldehydes is described. It has been carried out by using readily available reagents and operationally
simple conditions allowing the preparation of the acyclic C-nucleoside analogs in high yields. The
structure of these derivatives has been fully characterized by NMR correlations and single-crystal X-ray
diffraction. Some reactions also provide access to the corresponding tetrahydro-1,3-oxazines by an
alternative ring closure. Mechanistic considerations account for the observed steric course.
Crown Copyright Ó 2008 Published by Elsevier Ltd. All rights reserved.
Available online 25 April 2008
1. Introduction
saturated heterocycles.4 Since some 1-alkylamino-1-deoxyalditols
are commercially available, such as N-methyl, N-ethyl, and N-(2-
C-Nucleoside analogs in which an open-chain sugar is linked to
a heterocyclic moiety through a carbon–carbon bond represent
attractive structures in view of the biological and therapeutic ac-
tivities exhibited by naturally occurring C-nucleosides and their
synthetic surrogates.1
hydroxyethyl)-D-glucamine, and N-methyl-D-galactamine, we were
stimulated to further explore the preparation of new and robust
chiral 1,3-oxazolidines derived from aromatic aldehydes.
2. Results and discussion
Recently, we have shown that imines derived from sugar ami-
nopolyols, such as D-glucamine (1), can be converted into inherently
2.1. Synthesis of N-methyl-1,3-oxazolidines
chiral N-acyloxazolidines (3) under acylating conditions, a process
occurring through the intermediacy of a transient iminium ion
(Scheme 1).2 Both chiral oxazolidines and oxazolidinones have
proved to be versatile auxiliaries in asymmetric induction.3
Herein, we report the condensation of N-methyl-D-glucamine
(4) with different monosubstituted benzaldehydes (5a–5j, 5m, 5o,
5q) and polysubstituted benzaldehydes (5k, 5l), as well as 1-
naphthaldehyde (5n) and cinnamaldehyde (5p). Two protocols
were developed; the first (method A) involves the reaction of 4
with the corresponding aldehyde in water plus a small amount of
methanol to ensure homogenization, which causes the rapid sep-
aration of the adduct, either spontaneously or after solvent evap-
oration. In method B, a mixture of 4 and the aldehyde derivative is
refluxed in benzene with azeotropic water removal (Dean–Stark).
The resulting adducts are filtered from the hot benzene solution to
avoid crystallization of the remaining aldehyde.
In general, imines like RCH]NCH2CHOH–R1 are stable enough
and do not cyclize in solution; however, N-substitution leads to an
iminium species that further evolves to the corresponding 1,3-oxa-
zolidine. This strategy has in fact become the usual synthesis of such
Ac
Ar
N
CH2N=CH2Ar
OH
CH2NH2
OH
O
H
ArCHO
1) Ac2O, C5H5N
2) NH3, CH3OH
HO
HO
HO
OH
OH
CH2OH
OH
OH
CH2OH
OH
OH
CH2OH
CHO
CHO
CHO
CHO
CHO
Me
Me
Me
2
1
3
Scheme 1.
X
Me
Me
* Corresponding author.
E-mail address: rmarvaz@unex.es (R.F. Martınez).
5a-5j, 5m,
5o, 5q
5k
5l
5n
5p
´
0040-4020/$ – see front matter Crown Copyright Ó 2008 Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.04.082

6378
R.F. Mart´ınez et al. / Tetrahedron 64 (2008) 6377–6386
Table 1
in a ratio of w75:25 that increased up to 81:19 after crystalliza-
Isolated yields (%) in the condensation of 4 and aldehydes
tion from ethanol. Further recrystallizations, however, did not
alter that proportion nor did they facilitate stereoisomer
separation.
Entry
Aldehyde
X
Product
Yield (%) Aa/Bb
1
2
3
4
5
6
7
8
5a
5b
5c
5d
5e
5f
5g
5h
5i
4-NO2
3-MeO
3-Br
4-Cl
H
2-Me
3-Me
4-Me
4-Et
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
7þ8
80/93
79/92
76/95
70/97
57/97
18/96
60/91
79/90
With o-salicylaldehyde (5o) these methodologies gave rise to
a mixture of three products, which were identified as oxazolidines
9 (trans-configured) and 10 (cis), and the tetrahydro-1,3-oxazine 11
in an approximate proportion of 40:35:25, respectively, as de-
termined by 1H NMR integration. Similar results were obtained
with cinnamaldehyde (5p) affording a mixture of such five- and
six-membered heterocycles in 52:32:16 ratio (for 12/13/14, re-
spectively). In both cases, those proportions are identical by both
synthetic methods (A and B) and remain essentially unchanged
after successive crystallizations from ethanol. Separation of the
individual isomers could not be achieved.
The bifunctional aldehyde 5q reacted with 2 equiv of 4 in
aqueous medium with complete stereoselectivity as only com-
pound 15 could be isolated. This substance contains two oxazoli-
dine rings, both having the same configuration at the newly created
chiral centers (2R,20R) (vide infra) (Scheme 3).
9
41/98
76/84
31/85
10
11
12
13
14
15
5j
4-MeO
5k
5n
5o
5p
5q
98c/97c
61c/95c
47c/100c
51/57(87d)
2-OH
9þ10þ11
12þ13þ14
15
4-CHO
a
In water.
In benzene at reflux.
Combined yield.
b
c
d
Combined yield of 15–17.
CH2OH
As shown in Table 1, the latter protocol does usually produce higher
yields, substantially improved in a few cases with respect to the
aqueous variation, for which yields range from low, presumably
due to steric effects in the case of o-substituted aldehydes 5f and 5k
(entries 6 and 11), to good, especially with electron-withdrawing
groups (entries 1–4). No product could be obtained, either
HO
HO
Me
N
OH
H
H
CH2NHMe
OH
O
CHO
H
O
N
Me
H
HO
+
HO
by method
A
or by method B, starting from 2,4,6-trime-
OH
OH
CH2OH
OH
OH
CH2OH
thylbenzaldehyde (5l) and 4-dimethylaminobenzaldehyde (5m).
The absence of reactivity in 5m may be attributed to the strong
donor effect of the dimethylamino group that decreases the elec-
trophilic character of the carbonyl group. This argument has equally
been invoked to account for the inertness of 5m in the benzoin
condensation.5
CHO
4
5q
15
Scheme 3.
When these reactions were conducted with aldehydes 5a–5k,
the sole products were the corresponding trans-oxazolidines
6a–6k (Scheme 2), in which the new chiral center possesses R
configuration. With 1-naphthaldehyde (5n), its condensation with
4 led, in both methods A and B, to a mixture of trans- and cis-
oxazolidines (7 and 8, respectively). Both methods also gave 7/8
However, the same condensation conducted in refluxing ben-
zene provided a mixture of 15, its 2S,20S diastereomer (16), and the
isomeric bis-tetrahydro-1,3-oxazine 17 in an approximate pro-
portion of 66:22:12, respectively, from which pure 15 could be
isolated by crystallization from ethanol.
X
Me
Me
Me
CH2NHMe
OH
N
N
N
O
O
O
HO
H
HO
H
H
OH
OH
CH2OH
HO
HO
OH
OH
OH
OH
OH
OH
CH2OH
CH2OH
CH2OH
4
6a-6k
7
8
a X=4-NO2
b X=3-MeO
c X=3-Br
d X=4-Cl
e X=H
Me
Me
N
R
O
R
Me
N
N
R
O
H
H
O
HO
HO
HO
f
X=2-Me
H
g X=3-Me
h X=4-Me
OH
OH
CH2OH
OH
OH
OH
OH
i
X=4-Et
CH2OH
CH2OH
j
X=4-MeO
k X=2,4-Me2
9 R=2-HOC6H4
12 R=C6H5CH=CH
10 R=2-HOC6H4
13 R=C6H5CH=CH
11 R=2-HOC6H4
14 R=C6H5CH=CH
Scheme 2.

R.F. Mart´ınez et al. / Tetrahedron 64 (2008) 6377–6386
6379
A further proof supporting the heterocyclic nature of these
condensation products could be obtained through an acetylated
derivative of 6a, prepared by conventional room-temperature re-
action with acetic anhydride and pyridine. NMR analysis of the
crude mixture revealed the formation of approximately equal
amounts of 18 and 19; the latter could be isolated by evaporating to
dryness and treating the resulting oil with diethyl ether (Scheme 4).
CH2OH
CH2OH
HO
HO
HO
HO
H O
Me
N
Me
OH
H
H
H
N
O
HO
OH
H
O
N
Me
H
O
H
N
HO
H
Me
OH
OH
CH2OH
OH
OH
CH2OH
NO2
NO2
NO2
16
17
Me
Me
Me
N
N
N
O
2.2. Structural determination
O
O
H
H
H
Ac2O
Py
HO
AcO
AcO
+
Structural elucidation of the above substances can easily be
inferred from spectroscopic and analytical data. With the sole ex-
ception of IR bands at 3500–3100 cmꢀ1 (OH groups), no significant
absorptions are observed beyond 1600 cmꢀ1, in agreement with the
saturated character of the heterocycles. Tables 2 and 3 also collect
1H and 13C NMR chemical shifts of the heterocyclic moiety. The
proton resonances at w4.5 to 5.5 ppm and the 13C shift at w97 ppm
are consistent with the typical values encountered for the H-2 and
C-2 signals of the oxazolidine ring.6–8 Sugar carbons resonated at
around w71 ppm, another feature usually typical of acyclic poly-
hydroxyalkyl chains.9,10
Moreover, the mass spectrum of compound 6k showed frag-
mentations similar to those found in other polyhydroxylalkyl het-
erocycles such as Hetþ, Het–CH]OHþ, and Het–CHOHCH]OHþ,
which evidence the presence of the N-methyl-oxazolidine moiety
(Fig. 1S and Chart 1 in Supplementary data).
OH
OAc
OAc
OAc
CH2OAc
OH
CH2OH
OAc
CH2OAc
6a
18
19
Scheme 4.
The structure of 19 was in addition confirmed by X-ray diffrac-
tion analysis as suitable crystals were grown from ethanol solutions
(Fig. 1).11 NMR data of 19 (Tables 2 and 3) fully agree with those of
6a–6k, 7–10, 12, 13, 15, 16 and 18, thereby confirming the presence
of the oxazolidine core in these substances.
Crude mixtures resulting from the condensation of 4 with
aldehydes 5o–5q were analyzed by NMR analysis and evidenced
the presence of three isomeric substances having similar chemical
shifts and splitting patterns (Fig. 2S in Supplementary data). The
structure of tetrahydro-1,3-oxazine (attributed to minor products)
is based on spectroscopic data; proton and carbon resonances
(Tables 4 and 5) are close to those of the above oxazolidines and
were assigned by two-dimensional correlations.
Table 2
Selected chemical shifts (
d
, ppm) of the heterocyclic protons of chiral oxazolidinesa
Config.d
c
Product
H-2
H-5
H-4a
H-4b
DdH-4
6a
6e
6h
6j
7
8
15
16
18b
19b
4.75
4.56
4.51
4.48
5.21
5.48
4.56
4.70
4.77
4.71
4.32
4.28
4.25
4.24
4.37
4.28
4.26
4.18
4.38
4.24
3.35
3.33
3.34
3.30
3.29
3.14
3.32
3.08
2.48
3.24
2.42
2.37
2.34
2.31
2.54
2.85
2.35
2.67
2.50
2.76
0.93
0.96
1.00
0.99
0.75
0.29
0.97
0.41
0.98
0.48
R
R
R
R
R
S
R
S
R
S
2.3. Geometric isomerization of 1,3-oxazolidines
At this stage, it is worth pointing out that acetylation of 6a does
lead to not only the expected oxazolidine 18 but also 19. Further-
more, NMR monitoring of a CDCl3 solution of 19 revealed a slow
a
At 400 MHz, in DMSO-d6.
In CDCl3.
b
c
DdH-4
¼
dH-4a
ꢀ
dH-4b.
d
Stereochemistry at C-2.
Table 3
Selected 13C chemical shifts (
d
, ppm) of chiral oxazolidinesa
Polyhydroxyalkyl chain
Product
Heterocycle
C-2
C-4
C-5
N–Me
C-10
C-20
C-30
C-40
6a
6e
6j
7
8
96.0
97.6
97.2
96.9
96.1
95.8
96.9
97.4
98.1
97.5
98.3
96.7
98.0
57.0
57.2
57.0
57.4
53.6
56.5
55.2
57.1
55.4
57.3
55.8
57.2
56.4
79.8
79.1
78.7
78.4
77.8
79.3
77.8
78.9
77.8
79.3
77.9
76.0
75.4
37.7
37.5
37.4
38.0
39.4
37.5
38.0
38.0
38.8
37.7
38.6
37.6
38.1
71.4
71.4
71.3
71.4
71.4
71.6
71.8
71.6
71.5
71.6
71.6
70.2
70.9
71.3
71.4
71.3
71.3
71.2
71.6
71.7
71.6
71.3
71.5
71.5
68.7
69.2
71.3
71.3
71.2
71.3
71.2
71.5
71.6
71.6
71.2
71.5
71.5
68.1
68.0
63.6
63.7
63.6
63.7
63.6
68.8
63.9
63.9
64.0
63.8
64.0
61.7
61.7
Figure 1. ORTEP diagram for the N-methyl oxazolidine 19. Thermal ellipsoids were
drawn at 35% probability level.
9
10
12
13
15
16
18b
19b
Table 4
Chemical shifts (
oxazinesa
d, ppm) of the heterocyclic protons in N-Methyl-tetrahydro-1,3-
Product
H-2
H-4a
H-4b
H-5
OH-5
H-6
NCH3
11
14
17
4.63
4.26
4.59
3.04
2.93
3.00
2.56
2.60
2.68
3.82
3.70
3.74
5.22
4.96
5.00
4.21
4.13
4.26
2.00
2.21
2.09
a
At 100 MHz, in DMSO-d6.
In CDCl3.
b
a
At 400 MHz recorded in DMSO-d6.

6380
R.F. Mart´ınez et al. / Tetrahedron 64 (2008) 6377–6386
Table 5
(
Dd
DdH-4
¼
dH-4a
ꢀ
dH-4b) (Table 2). Such a difference increases to
Selected 13C resonances (
d
, ppm) of N-Methyl-tetrahydro-1,3-oxazinesa
trans
¼0.98 ppm for the isomeric structure 18 that does neces-
H-4
sarily possesses R configuration at C-2. These shift differences and
a nearly constant variation (DDdH-4
Product
Heterocycle
Polyhydroxyalkyl chain
trans
cis
¼Dd
ꢀ
Dd ¼0.5 ppm) may
C-2
C-4
C-5
C-6
N–Me
C-10
C-20
C-30
H-4
H-4
be employed as diagnostic criteria to denote the stereochemistry,
either R or S, in the rest of the synthesized oxazolidines. Data from
Table 2 plus those collected in Section 4 point to 2R-configured
products in the case of oxazolidines 6a–6k as well as major adducts
7, 9, 12, 15, and 18, whereas they are consistent with the opposite 2S
configuration in 8, 10, 13, 16, and 19. Again, these correlations are
11
14
17
94.7
94.8
95.7
59.9
60.4
60.7
73.7
74.0
74.0
77.7
77.6
78.3
39.8
39.8
39.7
70.9
70.9
70.9
66.1
66.9
66.8
63.1
63.2
63.1
a
At 100 MHz in DMSO-d6.
similar to those found in N-acyloxazolidines derived from D-gluc-
and gradual transformation of this substance into a mixture of 18
and 19 (Fig. 2). Since both derivatives are present in nearly equal
amounts after equilibration, their stability should be similar. This
isomerization should be occurring via acid catalysis. When acid
impurities present in CDCl3 are removed (by passing it through an
alumina column), such isomerization slows down. Thus, only 25%
and 38% of 18 is formed after 24 and 48 h, respectively (Fig. 3S in
Supplementary data). In contrast, this conversion was not detected
at all in DMSO-d6 (a solvent lacking acid character) after 6 days. This
behavior points to an easy isomerization between oxazolidines,
despite Baldwin rules disfavor a 5-endo-trig cyclization relative to
the 6-endo-trig one,12,13 which would afford the corresponding
oxazines. Nevertheless, David and co-workers have demonstrated
that 5-endo-trig cyclizations of imines and iminium ions leading
either to oxazolidines or to oxazines proceeds quickly.14
amine and corroborate the stereochemistry previously assigned to
these substances.2 Particular attention deserves the stereochemis-
try in adducts derived from 4 plus terephthaldehyde (5q) as four
different stereoisomers can be potentially formed as depicted in
Scheme 5: (2R,20R), (2R,20S), (2S,20R), and (2S,20S).
Me
N
Me
N
Me
N
Me
N
O
O
O
O
H
H
H
H
R
R
R
R
2R,2´S
20
2R,2´R
15
2.4. Absolute configuration at C-2 of chiral oxazolidines and
oxazines
Me
N
Me
N
Me
N
Me
N
O
O
O
O
H
H
H
H
R
R
R
R
Although the steric course of imine and iminium cyclization to
produce oxazolidines has been previously documented,4,15 such
pathways are not completely applicable to the present case with
the sole exception of N-acyloxazolidines.2 However, we were able
to establish unequivocally the absolute stereochemistry of the
newly generated stereocenter by spectroscopic correlation. The key
point of this reasoning is based on the stereochemistry at C-2 of
compound 19, which has been determined to be S (Fig. 1). NMR
2S,2´S
2S,2´R
21
16
R=D-arabino-(CHOH)3CH2OH
Scheme 5.
Obviously, the bis-oxazolidines with configurations (2R,20R) and
(2S,20S) possess a C2 symmetry axis that halves the expected proton
and carbon NMR signals; in stark contrast, the derivatives having
analysis shows that the two protons at C-4 of the oxazolidine ring
cis
exhibit very distinctive shifts with a difference Dd ¼0.48 ppm
H-4
Figure 2. Equilibration of isomers 18 and 19 in CDCl3 solution.

R.F. Mart´ınez et al. / Tetrahedron 64 (2008) 6377–6386
6381
HO
R
HO
R
considering solvent effects (CHCl3), in agreement with the experi-
mental observations.
R
Me
N
N
Me
R
Me
R
N
O
O
HO
O
2.6. Mechanistic considerations in the formation
of heterocyclic rings
R
2R (5C2)
2S (5C2)
2S (2C5)
Scheme 6 accounts for the formation of oxazolidines and tetra-
hydro-1,3-oxazines. The former substances are generated via 5-endo-
trig cyclization of the iminium ion, entropically favored with respect
tothealternative6-endo-trigthatprovides the1,3-oxazinederivative.
This stereochemical result assumes that cyclization of the (E)-
iminium cation occurs preferentially through the most stable
Figure 3. Conformations of tetrahydro-1,3-oxazines.
the (2R,20S) and (2S,20R) configurations would exhibit duplicated
signals. A detailed 13C NMR analysis of the crude sample reveals the
existence of three isomers, from which the major ones only show
the half of possible signals, thus agreeing with oxazolidines 15
(2R,20R) and 16 (2S,20S), whose stereochemistries have been
assigned through the magnitudes of DdH-4 (0.97 ppm and 0.43 ppm,
respectively). The minor adduct equally shows a simplified spec-
trum with the half of signals, a fact ruling out the isomers 20
(2R,20S) and 21 (2S,20R). Since its 13C resonances are different from
those of 15 and 16, the isomer should be the symmetrical bis(te-
trahydro-1,3-oxazine) 17.
conformation. The first and second chiral centers of N-methyl-D-
glucamine, having S and R configurations, respectively, as well as
their hydroxyl substituents lie in the Re face of the carbon of imi-
nium ion. The subsequent cyclization could then take place on such
a face to give a new chiral center with configuration R and relative
stereochemistry trans between the polyhydroxyl chain at C-5 and
the aromatic substituent at C-2.
N-Methyl-D-glucamine is not more stable in an extended zig-zag
(P) conformation (22) due to the 1,3-diaxial interaction present
between the hydroxyl groups at C-2 and C-4 rather this sugar
adopts a 3Gþ conformation (23) generated by 60ꢁ rotation around
the C3–C4 bond.20 A small rotation around the C–N bond converts
this initial conformation into a favored disposition (24) to reach the
transition structure that leads to a trans-oxazolidine (2R-config-
ured, 26, path a) by ring closure.
We have tentatively assigned an R configuration at C-2 for 11
and 14, and (2R,20R) for 17, because they lead to the most stable
conformation of the tetrahydro-1,3-oxazine: 5C2,16 which places the
bulkiest substituents in equatorial dispositions (Fig. 3). Moreover,
this argument is also consistent with the stereochemical outcome
that likely follows this transformation (vide infra).
Counterclockwise rotation at an angle of 120ꢁ around the C1–C2
bond then generates the 1Gꢀ3Gþ conformation (25), in which the
planar iminium group is placed between the hydroxyl groups of the
aforementioned carbon atoms; the first on the Si face and the other on
the Re face. Further cyclization of such hydroxyl groups gives rise to
a cis-oxazolidine (2S-configured, 27, path b) and a cis-tetrahydro-1,3-
oxazine (2R-configured, 28, path c), respectively, the former being
entropically favored. The 1Gꢀ3Gþ conformation (25) should be less
stable than 24 because the bulkier iminium group bisects the angle
between the hydroxyl substituent and the sugar chain, thereby gen-
erating two strong gauche interactions in addition to a 1,3-diaxial one
between the hydroxyl at C-2 and the iminium group. Conversely, only
one gauche interaction with the hydroxyl group occurs in 24. As a re-
sult, the transition structures leading to 27 and 28, which arise from
25, should likewise be less stable than the corresponding ones to 26
generated from the more stable conformation 24. Overall, this explains
why the relative amounts of products in experiments, i.e., 26>27>28
(kinetic control) contradicts the thermodynamic stability 26>28>27.
The 1Gꢀ3Gꢀ conformation, generated by clockwise rotation at an
angle of 120ꢁ around the C1–C2 bond, has a lower energy than that
of 1Gꢀ3Gþ (25); however, such an arrangement puts away the
iminium group, thus impeding the ring closure.
2.5. Stability of N-methyl oxazolidines and N-methyl-
tetrahydro-1,3-oxazines
Calculations in vacuum at the DFT level (B3LYP/6-31G
*
) of
theory,17 and with a PCM(B3LYP/6-31G ) SCRF model18 to consider
*
the solvent, have also been carried out using Gaussian 0319 to asses
the relative stability of the different isomeric species. As repre-
sentative example, Table 6 shows the computed energies for oxa-
zolidines 9 and 10 and their isomeric oxazine 11. In the gas phase,
the oxazine derivative has a larger stability, while compound 9
becomes more stable in DMSO. It is noteworthy that energy dif-
ferences between 9 and 10 remain constant in both gas phase and
after considering solvent effects. Accordingly, the experimental ratio
9>10>11 (40:35:25, respectively) follows a different trend to ther-
modynamic stability and reflects that formation of these heterocyclic
species should be occurring under kinetic control. This conclusion
may be extrapolated to other series such as 12–14 and 15–17.
Table 7 shows the calculated energies for the trans- and cis-
acetylated oxazolidines 18 and 19. Such calculations evidence the
same stability of both isomers, in the gas phase as well as by
Table 6
Alternative to the cyclization through the Si face of (E)-iminium
cation, cyclization of the C-2 hydroxyl group through the Re face of
the (Z)-iminium cation would give rise to a cis-oxazolidine, as well
as the corresponding cis-oxazine resulting from the cyclization of
the hydroxyl group at C-3. However, the latter has not been
detected experimentally.
Finally, equilibration between trans- and cis-oxazolidines (18
and 19) should be occurring under acid catalysis, a fact that re-
generates the cation intermediate (30).
Calculated relative energies of compounds 9–11a
Product
9
10
11
Vacuumb
DMSOc
12.17
0.00
18.12
7.29
0.00
2.38
a
b
c
In kcal molꢀ1
At the B3LYP/6-31G
.
*
level.
PCM(B3LYP/6-31G ) SCRF.
*
Table 7
Calculated relative energies of compounds 18 and 19a
Me
Me
Me
Product
18
19
N
N
N
HA
Ar
Vacuumb
0.82
0.59
0.00
0.00
Ar
19
18
OH
c
O
H
O
H
CHCl3
H
Ar
HA
HO
HO
HO
R
a
In kcal molꢀ1
At the B3LYP/6-31G
.
R
R
31
29
30
b
c
*
level.
(R=D-erythro-CHOAcCHOAcCH2OAc; Ar=4-NO2C6H4)
PCM(B3LYP/6-31G
*
) SCRF.

6382
R.F. Mart´ınez et al. / Tetrahedron 64 (2008) 6377–6386
a
path a
Me
Me
Ar
N
Me
N
R
OH
OH OH
R
OH
Me
Ar
H
Re attack
path a
O
OH
N
Ar
HOCH2
HO
Ar
N
HO
HO
HO
OH
OH
OH
24
H
H
R
path c
26
22 (P)
23 (3G+)
Me
OH
R
HO
Me
path b
H
N
N
path c
Re attack
path b
Si attack
Me
O
28
Ar
HO
O
OH
R
HO
Ar
HO
N
OH
R
path c
27
Ar
25 (1G-3G+)
(R = D-glycero-CHOH-CH2OH)
Scheme 6.
In solvents devoid of such properties (e.g., DMSO), no equilibration
takes place.
concomitant water removal (Dean–Stark). The product was filtered
and washed with cold benzene and recrystallized from ethanol.
4.2.1. (2R,5S)-3-Methyl-2-(4-nitrophenyl)-5-(
D
-arabino-1,2,3,4-
3. Conclusions
tetrahydroxybutyl)oxazolidine (6a)
22
Method A (80%); method B (93%); mp 160–162 ꢁC; [
a
]
þ11 (c
D
In summary, we have demonstrated a convenient one-pot pro-
tocol for the formation of chiral oxazolidines with high or complete
stereoselectivity from N-methylaminopolyols and aromatic alde-
hydes bypassing the Schiff base stage. Given the availability of
N-alkyl-D-glycamines, this methodology should facilitate access to
mono- and bis-C-glycosylated oxazolidines (and oxazines) as suit-
0.5, pyridine); nmax/cmꢀ1 3400–3200 (OH), 1605, 1520, 1457 (arom),
1085, 1030 (C–O). 1H NMR (400 MHz, DMSO-d6, ppm)
d
8.23 (d, J
8.8 Hz, 2H, H-arom), 7.71 (d, J 8.8 Hz, 2H, H-arom), 4.75 (s, 1H, H-2),
4.62 (d, J 6.4 Hz, 1H, OH), 4.52 (d, J 6.0 Hz, 1H, OH), 4.36 (d, J 4.0 Hz,
1H, OH), 4.35 (t, J4 ,OH¼J4 ,OH 3.0 Hz, 1H, OH-40), 4.32 (dt, J4a,5¼J5,1
0
00
0
0
0
0
0
6.6 Hz, J4b,5 9.2 Hz, 1H, H-5), 3.70 (t, J1 ,5¼J1 ,OH 7.4 Hz, J1 ,2 0 Hz, 1H,
able scaffolds.
H-10), 3.60 (m, J4 ,OH 3.2 Hz, J3 ,4 5.6 Hz, 1H, H-4 ), 3.50 (m, 1H, H-3 ),
0
0
0
0
0
3.42 (dt, J4 ,4 11.2 Hz, J4 ,3 ¼J4 ,OH 5.6 Hz, 1H, H-400), 3.35 (dd, J4a,4b
00
0
00
0
00
4. Experimental
4.1. General
9.4 Hz, J4a,5 5.8 Hz, 1H, H-4a), 3.22 (t, J2 ,3 ¼J2 ,OH 7.8 Hz, 1H, H-20),
0
0
0
0
2.42 (t, J4a,4b¼J4b,5 9.4 Hz, 1H, H-4b), 2.14 (s, 3H, CH3). 13C NMR
(100 MHz, DMSO-d6, ppm)
d 148.03 (C-arom), 147.24 (C-arom),
129.24 (2C, C-arom), 123.59 (2C, C-arom), 96.02 (C-2), 79.76 (C-5),
71.36, 71.27 (C-10, C-20, C-30), 63.60 (C-40), 57.05 (C-4), 37.67 (CH3–
N). Anal. Calcd for C14H20N2O7: C, 51.22; H, 6.14; N, 8.53. Found: C,
51.20; H, 6.35; N, 8.60.
Melting points were determined on Gallenkamp and Electro-
thermal apparatus, and are uncorrected. Optical rotations were
measured on a Perkin–Elmer 241 polarimeter. IR spectra were
recorded in the range 4000–600 cmꢀ1 on FT-IR THERMO spectro-
photometer. Solid samples were recorded on KBr (Merck) pellets.
1H and 13C NMR spectra were recorded on a Bruker 400 AC/PC
instrument at 400 and 100 MHz, respectively, or with a Bruker AC
200-E instrument at 200 and 50.3 MHz, respectively, in different
solvent systems. Assignments were confirmed by homo- and het-
ero-nuclear double-resonance and DEPT (distortionless enhance-
ment by polarization transfer). TMS was used as the internal
4.2.2. (2R,5S)-2-(3-Methoxyphenyl)-3-methyl-5-(D-arabino-
1,2,3,4-tetrahydroxybutyl)oxazolidine (6b)
23
Method A (79%); method B (92%); mp 133–135 ꢁC; [
a
]
þ12 (c
D
0.5, pyridine); nmax/cmꢀ1 3500–3100 (OH), 1603 (arom), 1160, 1097,
1031 (C–O). 1H NMR (400 MHz, DMSO-d6, ppm)
d
7.29 (t, J 7.8 Hz,
1H, H-arom), 7.00 (m, 2H, H-arom), 6.91 (dd, J 1.8, 7.8 Hz, 1H, H-
arom), 4.58 (d, J 6.0 Hz, 1H, OH), 4.54 (s, 1H, H-2), 4.34 (m, 2H, OH),
standard (
d
¼0.00 ppm) and all J values are given in hertz. Micro-
0
4.27 (dt, J4a,5¼J4b,5 8.8 Hz, J5,1 6.4 Hz, 1H, H-5), 3.69 (s, 3H, OCH3),
analyses were carried out on a Leco 932 analyser at the Universidad
de Extremadura (Spain). High resolution mass spectra (chemical
ionization) were recorded on an Autospec-Q spectrometer by the
Servicio de Espectrometr´ıa de Masas de la Universidad de Sevilla
(Spain).
3.68 (t, J1 ,5¼J1 ,OH 6.0 Hz, J1 ,2 0 Hz, 1H, H-10), 3.60 (d, J4 ,4 10.0 Hz,
0
0
0
0
0
00
1H, H-40), 3.50 (m, 1H, H-30), 3.42 (m, 1H, H-400), 3.32 (dd, J4a,4b
8.8 Hz, J4a,5 5.6 Hz, 1H, H-4a), 3.21 (t, J2 ,3 6.8 Hz, 1H, H-20), 2.34 (t,
J4a,4b¼J4b,5 9.4 Hz, 1H, H-4b), 2.00 (s, 3H, CH3). 13C NMR (100 MHz,
0
0
DMSO-d6, ppm)
d 159.40, 141.21, 129.38, 120.55, 114.64, 113.31 (C-
arom), 97.38 (C-2), 79.10 (C-5), 71.42, 71.36, 71.30 (C-10, C-20, C-30),
63.66 (C-40), 57.11 (C-4), 55.29 (OCH3), 37.61 (CH3). Anal. Calcd for
4.2. Condensation of N-methyl-
D-glucamine with aldehydes
C15H23NO6: C, 57.50; H, 7.40; N, 4.47. Found: C, 57.32; H, 7.65; N,
Method A. To a solution of N-methyl-
D
-glucamine (55.2 mmol) in
4.62.
water (70 mL) was slowly added a solution of the corresponding
aldehyde (55.0 mmol) in a few volume of methanol. The mixture
was stirred at room temperature, which afforded a precipitate
within few minutes. The resulting product was collected by filtra-
tion, successively washed with cold water, ethanol, and diethyl
ether, and recrystallized from ethanol.
4.2.3. (2R,5S)-2-(3-Bromophenyl)-3-methyl-5-(
D
-arabino-1,2,3,4-
tetrahydroxybutyl)oxazolidine (6c)
21
Method A (76%); method B (95%); mp 166–168 ꢁC; [
a
]
þ7 (c
D
0.5, pyridine); nmax/cmꢀ1 3400–3200 (OH), 1578, 1474 (arom), 1090,
1024 (C–O). 1H NMR (400 MHz, DMSO-d6, ppm)
d
7.61 (s, 1H, H-
Method B. To
a
suspension of N-methyl-
D
-glucamine
arom), 7.55 (d, J 8.0 Hz, 1H, H-arom), 7.43 (d, J 8.0 Hz, 1H, H-arom),
7.34 (t, J 7.7 Hz,1H, H-arom), 4.58 (d, J 4.4 Hz,1H, OH), 4.56 (s,1H, H-
2), 4.50 (d, J 5.6 Hz, 1H, OH), 4.34 (t, J 6.0 Hz, 1H, OH), 4.26 (m, 1H,
(10.0 mmol) in benzene (15 mL) was added the corresponding al-
dehyde (15.0 mmol). The mixture was refluxed for 4–5 h with

R.F. Mart´ınez et al. / Tetrahedron 64 (2008) 6377–6386
6383
H-5), 3.66 (t, J1 ,5¼J1 ,OH 6.8 Hz, J1 ,2 0 Hz, 1H, H-10), 3.58 (m, 1H, H-
7.15 (d, J 7.20 Hz, 1H, H-arom), 4.55 (d, J 6.8 Hz, 1H, OH), 4.51 (s, 1H,
H-2), 4.50 (d, J 6.4 Hz, 1H, OH), 4.34 (t, J 5.6 Hz, 1H, OH), 4.31 (d, J
0
0
0
0
40), 3.48 (m, 1H, H-30), 3.40 (dt, J4 ,OH¼J4 ,3 5.6 Hz, J4 ,4 11.2 Hz, 1H,
00
00
0
00
0
H-400), 3.31 (dd, J4a,4b 8.8 Hz, J4a,5 6.0 Hz, 1H, H-4a), 3.20 (t,
7.6 Hz, 1H, OH), 4.26 (m, 1H, H-5), 3.67 (t, J1 ,5 6.8 Hz, J1 ,OH 6.4 Hz,
0
0
J2 ,3 ¼J2 ,OH 7.8 Hz, 1H, H-20), 2.35 (t, J4b,4a¼J4b,5 9.2 Hz, 1H, H-4b),
J1 ,2 0 Hz, 1H, H-10), 3.59 (m, 1H, H-40), 3.49 (m, 1H, H-30), 3.40
0
0
0
0
0
2.10 (s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6, ppm)
d
138.38,
(dt, J4 ,OH¼J4 ,3 5.6 Hz, J4 ,4 10.9 Hz,1H, H-4 ), 3.32 (dd, J4a,4b 8.9 Hz,
00
00
00
0
00
0
0
0
0
133.18, 129.80, 128.09 (C-arom), 96.30 (C-2), 79.98 (C-5), 71.07,
71.00, 70.93 (C-10, C-20, C-30), 63.33 (C-40), 56.77 (C-4), 37.30 (CH3).
Anal. Calcd for C14H20BrNO5: C, 46.42; H, 5.57; N, 3.87. Found: C,
46.27; H, 5.88; N, 4.06.
J4a,5 5.8 Hz, 1H, H-4a), 3.21 (t, J2 ,3 ¼J2 ,OH 7.4 Hz, 1H, H-20), 2.34 (t,
J4b,4a¼J4b,5 8.8 Hz, 1H, H-4b), 2.31 (s, 3H, CH3–arom), 2.08 (s, 3H,
CH3). 13C NMR (100 MHz, DMSO-d6, ppm)
d 139.19, 137.11, 129.33,
128.43, 127.85, 125.13 (C-arom), 97.28 (C-2), 78.75 (C-5), 71.03,
70.97 (C-10, C-20, C-30), 63.34 (C-40), 56.85 (C-4), 37.27 (CH3), 20.94
(CH3–arom). Anal. Calcd for C15H23NO5: C, 60.59; H, 7.80; N, 4.71.
Found: C, 60.39; H, 7.68; N, 4.79.
4.2.4. (2R,5S)-2-(4-Chlorophenyl)-3-methyl-5-(
D
-arabino-1,2,3,4-
tetrahydroxybutyl)oxazolidine (6d)
22
Method A (70%); method B (97%); mp 193–195 ꢁC; [
a]
þ6 (c 0.5,
D
pyridine); nmax/cmꢀ1 3400–3200 (OH), 1602, 1492, 1459 (arom),
4.2.8. (2R,5S)-3-Methyl-2-(4-methylphenyl)-5-(D-arabino-1,2,3,4-
1088, 1032 (C–O). 1H NMR (400 MHz, DMSO-d6, ppm)
d
7.46 (d, J
tetrahydroxybutyl)oxazolidine (6h)
21
8.8 Hz, 2H, H-arom), 7.43 (d, J 8.8 Hz, 2H, H-arom), 4.59 (d, J 6.8 Hz,
1H, OH), 4.57 (s, 1H, H-2), 4.51 (d, J 5.6 Hz, 1H, OH), 4.35 (t, J 5.6 Hz,
Method A (79%); method B (90%); mp 170–172 ꢁC; [
a]
þ11 (c
D
0.5, pyridine); nmax/cmꢀ1 3400–3100 (OH), 1457 (arom), 1062, 1029
0
0
1H, OH), 4.34 (d, J 7.6 Hz,1H, OH), 4.26 (m,1H, H-5), 3.67 (t, J1 ,5¼J1 ,OH
(C–O). 1H NMR (400 MHz, DMSO-d6, ppm)
d
7.31 (d, J 7.6 Hz, 2H, H-
0
0
0
0
0
6.8 Hz, J1 ,2 0 Hz,1H, H-1 ), 3.59 (m,1H, H-4 ), 3.49 (m,1H, H-3 ), 3.40
arom), 7.17 (d, J 7.6 Hz, 2H, H-arom), 4.54 (d, J 5.2 Hz, 1H, OH), 4.51
(s, 1H, H-2), 4.50 (d, 1H, OH), 4.30 (m, 2H, OH), 4.25 (c,
(m,1H, H-400), 3.32 (m,1H, H-4A), 3.20 (t, J2 ,3 ¼J2 ,OH 7.6 Hz,1H, H-20),
0
0
0
2.35 (t, J4b,4a¼J4b,5 9.2 Hz, 1H, H-4b), 2.12 (s, 3H, CH3). 13C NMR
J4a,5¼J4b,5¼J5,1 7.2 Hz, 1H, H-5), 3.67 (t, J1 ,5¼J1 ,OH 6.4 Hz, J1 ,2 0 Hz,
0
0
0
0
0
1H, H-10), 3.59 (dd, J4 ,4 10.0 Hz, J4 ,3 5.0 Hz, 1H, H-40), 3.49 (m, 1H,
0
0
0
0
0
(100 MHz, DMSO-d6, ppm)
d
138.89,133.70,130.31,128.61 (C-arom),
96.16 (C-2), 79.11 (C-5), 71.07, 70.95 (C-10, C-20, C-30), 63.32 (C-40),
56.71 (C-4), 37.30 (CH3). Anal. Calcd for C14H20ClNO5: C, 52.92; H,
6.34; N, 4.41. Found: C, 53.10; H, 6.35; N, 4.35.
H-30), 3.41 (dt, J4 ,4 10.8 Hz, J4 ,3 ¼J4 ,OH 5.6 Hz, 1H, H-400), 3.34 (dd,
00
0
00
0
00
0
0
0
0
J4a,4b 8.4 Hz, J4a,5 6.4 Hz, 1H, H-4a), 3.21 (t, J2 ,3 zJ1 ,2 7.6 Hz, 1H, H-
20), 2.34 (t, J4a,4b¼J4b,5 9.6 Hz, 1H, H-4b), 2.06 (s, 3H, CH3). 13C NMR
(100 MHz, DMSO-d6, ppm)
d 138.18 (C-arom), 136.51 (C-arom),
4.2.5. (2R,5S)-3-Methyl-2-phenyl-5-(
D
-arabino-1,2,3,4-
128.80 (2C, C-arom), 128.17 (2C, C-arom), 97.38 (C-2), 78.91 (C-5),
71.33, 71.27, 71.21 (C-10, C-20, C-30), 63.60 (C-40), 57.11 (C-4), 37.46
(CH3–N), 21.08 (CH3). Anal. Calcd for C15H23NO5: C, 60.59; H, 7.80;
N, 4.71. Found: C, 60.33; H, 7.64; N, 4.84.
tetrahydroxybutyl)oxazolidine (6e)
21
Method A (57%); method B (97%); mp 129–131 ꢁC; [
a
]
þ12 (c
D
0.5, pyridine); IR (KBr) nmax/cmꢀ1 3400–3100 (OH), 1477, 1457
(arom),1095, 1024 (C–O). 1H NMR (400 MHz, DMSO-d6, ppm)
d
7.44
(m, 2H, H-arom), 7.36 (m, 3H, H-arom), 4.57 (d, J 6.4 Hz, 1H, OH),
4.56 (s, 1H, H-2), 4.51 (d, J 5.6 Hz, 1H, OH), 4.35 (d, J 5.2 Hz, 1H, OH),
4.2.9. (2R,5S)-2-(4-Ethylphenyl)-3-methyl-5-(
D
-arabino-1,2,3,4-
tetrahydroxybutyl)oxazolidine (6i)
20
4.34 (t, J 7.6 Hz, 1H, OH), 4.28 (m, J5,4b 8.8 Hz, J5,1 6.4 Hz, 1H, H-5),
Method A (41%); method B (98%); mp 133–135 ꢁC; [
a
]
þ8 (c
0
D
3.70 (dd, J1 ,5¼J1 ,OH 6.0 Hz, J1 ,2 0 Hz, 1H, H-10), 3.61 (dd, J4 ,4
0.5, pyridine); nmax/cmꢀ1 3400–3200 (OH), 1490,1454 (arom), 1093,
0
0
0
0
0
00
11.0 Hz, J4 ,3 2.6 Hz, 1H, H-40), 3.51 (m, 1H, H-30), 3.42 (dt, J4 ,4
1033 (C–O). 1H NMR (400 MHz, DMSO-d6, ppm)
d
7.33 (d, J 7.6 Hz,
0
0
00
0
10.6 Hz, J4 ,3 ¼J4 ,OH 5.6 Hz, 1H, H-400), 3.33 (dd, J4a,4b 8.8 Hz, J4a,5
2H, H-arom), 7.20 (d, J 8.0 Hz, 2H, H-arom), 4.55 (d, J 6.4 Hz, 1H,
OH), 4.52 (s, 1H, H-2), 4.51 (d, J 6.0 Hz, 1H, OH), 4.36 (t, J 5.6 Hz, 1H,
00
0
00
6.0 Hz, 1H, H-4a), 3.24 (t, J2 ,3 ¼J2 ,OH 6.8 Hz, 1H, H-20), 2.37 (t,
0
0
0
J4b,4a¼J4b,5 9.0 Hz, 1H, H-4b), 2.09 (s, 3H, CH3). 13C NMR (100 MHz,
OH), 4.32 (d, J 7.2 Hz, 1H, OH), 4.25 (m, 1H, H-5), 3.67 (t, J1 ,5¼J1 ,OH
0
0
6.4 Hz, J1 ,2 0 Hz, 1H, H-10), 3.59 (m, 1H, H-40), 3.49 (m, 1H, H-30),
0
0
DMSO-d6, ppm) d 139.54, 129.05, 128.32, 128.26 (C-arom), 97.57 (C-
2), 79.13 (C-5), 71.42, 71.36, 71.30 (C-10, C-20, C-30), 63.69 (C-40),
57.17 (C-4), 37.55 (CH3). Anal. Calcd for C14H21NO5: C, 59.35; H, 7.47;
N, 4.94. Found: C, 59.02; H, 7.42; N, 5.10.
3.40 (m, 1H, H-400), 3.32 (dd, J4a,4b 8.8 Hz, J4a,5 6.0 Hz, 1H, H-4a), 3.21
(t, J2 ,3 ¼J2 ,OH 7.6 Hz, 1H, H-20), 2.60 (c, J 7.6 Hz, 2H, CH2–Ar), 2.34 (t,
J4b,4a¼J4b,5 9.2 Hz, 1H, H-4b), 2.08 (s, 3H, CH3), 1,18 (t, J 7.6 Hz, 3H,
0
0
0
CH3–Ar). 13C NMR (100 MHz, DMSO-d6, ppm)
d 144.81, 137.00,
4.2.6. (2R,5S)-3-Methyl-2-(2-methylphenyl)-5-(
D
-arabino-1,2,3,4-
128.47, 127.89 (C-arom), 97.66 (C-2), 79.14 (C-5), 71.59, 71.54, 71.46
(C-10, C-20, C-30), 63.85 (C-40), 57.36 (C-4), 37.77 (CH3), 28.44 (CH2–
Ar), 16.08 (CH3–Ar). Anal. Calcd for C16H25NO5: C, 61.72; H, 8.09; N,
4.50. Found: C, 61.55; H, 8.20; N, 4.46.
tetrahydroxybutyl)oxazolidine (6f)
20
Method A (18%); method B (96%); mp 110–112 ꢁC; [
a
]
þ22 (c
D
0.5, pyridine); nmax/cmꢀ1 3400–3200 (OH), 1453 (arom), 1057, 1031
(C–O). 1H NMR (400 MHz, DMSO-d6, ppm)
d
7.43 (d, J 7.2 Hz, 1H, H-
arom), 7.20 (m, 3H, H-arom), 4.81 (s, 1H, H-2), 4.55 (d, J 6.4 Hz, 1H,
OH), 4.50 (d, J 5.2 Hz, 1H, OH), 4.34 (m, 2H, OH), 4.23 (dt, J4a,5¼J4b,5
4.2.10. (2R,5S)-2-(4-Methoxyphenyl)-3-methyl-5-(
D
-arabino-
1,2,3,4-tetrahydroxybutyl)oxazolidine (6j)
22
0
0
0
0
0
8.8 Hz, J5,1 6.6 Hz, 1H, H-5), 3.68 (t, J1 ,5¼J1 ,OH 6.2 Hz, J1 ,2 0 Hz, 1H,
Method A (76%); method B (84%); mp 170–172 ꢁC; [
a
]
þ11 (c
D
H-10), 3.58 (m, 1H, H-40), 3.49 (m, 1H, H-30), 3.40 (dt, J4 ,4 10.0 Hz,
0.5, pyridine); nmax/cmꢀ1 3400–3100 (OH), 2960 (OCH3), 1613, 1515
00
0
J4 ,3 ¼J4 ,OH 5.0 Hz, 1H, H-400), 3.31 (m, 1H, H-4a), 3.21 (t, J2 ,3 ¼J1 ,2
(arom), 1097, 1032 (C–O). 1H NMR (400 MHz, DMSO-d6, ppm)
d
7.34
00
0
00
0
0
0
0
7.6 Hz, 1H, H-20), 2.41 (t, 1H, H-4b), 2.38 (s, 3H, CH3–arom), 2.08 (s,
(t, J 8.4 Hz, 1H, H-arom), 6.91 (d, J 8.4 Hz, 2H, H-arom), 4.54 (d, J
6.4 Hz, 1H, OH), 4.48 (s, 1H, H-2), 4.33 (m, 2H, OH), 4.29 (d, J 7.6 Hz,
1H, OH), 4.24 (m, J4a,5¼J4b,5 8.7 Hz, 1H, H-5), 3.75 (s, 3H, OCH3), 3.65
3H, CH3). 13C NMR (100 MHz, DMSO-d6, ppm)
d 137.08, 136.19,
130.44, 128.24, 128.10, 125.44 (C-arom), 95.21 (C-2), 78.07 (C-5),
71.12, 71.06, 71.00 (C-10, C-20, C-30), 63.34 (C-40), 56.67 (C-4), 37.15
(CH3–N), 18.59 (CH3). Anal. Calcd for C15H23NO5$1⁄2 H2O: C, 58.81;
H, 7.90; N, 4.57. Found: C, 59.05; H, 8.04; N, 4.89.
(t, J1 ,5¼J1 ,OH 6.8 Hz, J1 ,2 0 Hz, 1H, H-10), 3.580(m, J4 ,4 10.3 Hz, J4 ,OH
0
0
0
0
0
00
0
0
0
0
00
00
0
5.4 Hz, J4 ,3 3.6 Hz, 1H, H-4 ), 3.47 (m, 1H, H-3 ), 3.38 (dt, J4 ,OH¼J4 ,3
00
00
0
5.2 Hz, J4 ,4 11.2 Hz, 1H, H-4 ), 3.30 (dd, J4a,4b 8.8 Hz, J4a,5 6.0 Hz, 1H,
H-4a), 3.20 (t, J2 ,3 ¼J2 ,OH 7.4 Hz, 1H, H-20), 2.31 (t, J4a,4b¼J4b,5 9.0 Hz,
0
0
0
4.2.7. (2R,5S)-3-Methyl-2-(3-methylphenyl)-5-(D-arabino-1,2,3,4-
1H, H-4b), 2.06 (s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6, ppm)
tetrahydroxybutyl)oxazolidine (6g)
d 159.83, 131.35, 129.47, 113.61 (C-arom), 97.20 (C-2), 78.73 (C-5),
21
Method A (60%); method B (91%); mp 165–167 ꢁC; [
a]
þ14 (c
71.33, 71.27, 71.18 (C-10, C-20, C-30), 63.60 (C-40), 57.05 (C-4), 55.29
(OCH3), 37.40 (CH3). Anal. Calcd for C15H23NO6$1⁄2 H2O: C, 55.89; H,
7.50; N, 4.35. Found: C, 55.97; H, 7.38; N, 4.47.
D
0.5, pyridine); nmax/cmꢀ1 3400–3200 (OH), 1479, 1458 (arom), 1035
(C–O). 1H NMR (400 MHz, DMSO-d6, ppm)
7.22 (m, 3H, H-arom),
d

6384
R.F. Mart´ınez et al. / Tetrahedron 64 (2008) 6377–6386
4.2.11. (2R,5S)-2-(2,4-Dimethylphenyl)-3-methyl-5-(
D
-arabino-
4.2.13.2. Spectroscopic data for compound 10y. 1H NMR (400 MHz,
DMSO-d6, ppm) 7.20 (m, 1H, H-arom), 6.76 (m, 3H, H-arom), 4.87
1,2,3,4-tetrahydroxybutyl)oxazolidine (6k)
d
20
Method A (31%); method B (85%); mp 148–150 ꢁC; [
a]
þ14 (c
(s, 1H, H-2), 4.21 (m, 1H, H-5), 3.67 (m, 1H, H-10), 3.60 (m, 1H, H-40),
D
0.5, pyridine); nmax/cmꢀ1 3500–3100 (OH), 1600 (arom), 1161.64,
3.56 (m, 1H, 30), 3.48 (m, 1H, H-400), 3.36 (d, J2 ,3 6.4 Hz, 1H, H-20),
3.14 (dd, J4a,4b 7.6 Hz, J4a,5 4.4 Hz, 1H, H-4a), 2.69 (t, J4a,4b¼J4b,5
8.8 Hz, 1H, H-4b), 2.22 (s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6,
0
0
1082.3, 1031.39 (C–O). 1H NMR (400 MHz, DMSO-d6, ppm)
d
7.31 (d,
J 7.6 Hz, 1H, H-arom), 6.99 (d, J 7.6 Hz, 1H, H-arom), 6.98 (s, 1H, H-
arom), 4.76 (s, 1H, H-2), 4.55 (m, 2H, OH), 4.34 (m, 2H, OH), 4.22 (m,
1H, H-5), 3.68 (m, 1H, H-10), 3.60 (m, 1H, H-40), 3.48 (m, 1H, H-30),
ppm)
d 157.74–116.03 (C-arom), 96.89 (C-2), 77.81 (C-5), 71.76,
71.65, 71.62 (C-10, C-20, C-30), 63.90 (C-40), 55.21 (C-4), 37.99 (CH3).
3.40 (m, 1H, H-400), 3.33 (m, 1H, H-4a), 3.21 (t, J2 ,3 ¼J2 ,OH 7.6 Hz, 1H,
H-20), 2.37 (t, J4b,4a¼J4b,5 9.4 Hz, 1H, H-4b), 2.34 (s, 3H, CH3–arom),
2.25 (s, 3H, CH3–arom), 2.05 (s, 3H, CH3). 13C NMR (100 MHz,
0
0
0
4.2.13.3. Spectroscopic data for compound 11y. 1H NMR (400 MHz,
DMSO-d6, ppm) d 7.57 (d, J 7.6 Hz, 1H, H-arom), 7.41 (d, J 8.4 Hz, 1H,
DMSO-d6, ppm)
d
137.60, 137.14, 133.50, 131.32, 128.53, 126.26
H-arom), 6.84 (d, J 8.4 Hz,1H, H-arom), 5.22 (br s,1H, OH-5), 4.63 (s,
1H, H-2), 4.21 (m, 1H, H-6), 3.82 (m, 1H, H-5), 3.67–3.04 (m, 4H, H-
10, H-20, H-30, H-300), 3.04 (dd, J4a,4b 12.4 Hz, J4a,5 2.4 Hz, 1H, H-4a),
2.56 (d, J4a,4b 12.4 Hz, 1H, H-4b), 2.00 (s, 3H, CH3). 13C NMR
(C-arom), 95.53 (C-2), 78.25 (C-5), 71.39, 71.33, 71.27 (C-10, C-20, C-
30), 63.63 (C-40), 57.26 (C-4), 37.73 (CH3), 20.93, 18.80 (CH3–arom).
HRMS-CI (C16H26NO5[MþH]þ) calcd: 312.181098; found:
312.181732.
(100 MHz, DMSO-d6, ppm)
d 156.84–116.03 (C-arom), 94.71 (C-2),
77.66 (C-6), 73.71 (C-5), 70.88, 66.10 (C-10, C-20), 63.08 (C-30), 59.90
(C-4), 39.87 (CH3).
4.2.12. (2R,5S)-3-Methyl-2-(1-naphthyl)-5-(
tetrahydroxybutyl)oxazolidine (7) and (2S,5S)-3-methyl-2-(1-
naphthyl)-5-( -arabino-1,2,3,4-tetrahydroxybutyl)oxazolidine (8)
D-arabino-1,2,3,4-
D
4.2.14. (2R,5S)-3-Methyl-2-styryl-5-(
tetrahydroxybutyl)oxazolidine (12), (2S,5S)-3-methyl-2-
styryl-5-( -arabino-1,2,3,4-tetrahydroxybutyl)oxazolidine
(13), and (2R,5R)-5-hydroxy-3-methyl-2-styryl-5-(
D-arabino-1,2,3,4-
Method A (98); method B (97%); ratio 75:25 (7/8); mp 154–
21
157 ꢁC; [
a]
þ9 (c 0.5, pyridine); nmax/cmꢀ1 3400–3100 (OH), 1589,
D
D
1506, 1452 (arom), 1070, 1028 (C–O). Anal. Calcd for C18H23NO5: C,
64.85; H, 6.95; N, 4.20. Found: C, 64.62; H, 7.15; N, 4.21.
D-
erythro-1,2,3-trihydroxypropyl)tetrahydro-1,3-oxazine (14)
Method A (47%); method B (100%); ratio 52:32:16 (12/13/14).
4.2.12.1. Spectroscopic data for compound 7. 1H NMR (400 MHz,
DMSO-d6, ppm)
d
8.49 (d, J 7.6 Hz, 1H, H-arom), 7.93 (m, 2H, H-
4.2.14.1. Spectroscopic data for compound 12. 1H NMR (400 MHz,
arom), 7.67 (d, J 7.2 Hz, 1H, H-arom), 7.51 (m, 3H, H-arom), 5.21 (s,
1H, H-2), 4.55 (d, J 4.4 Hz,1H, OH), 4.50 (d, J 6.0 Hz,1H, OH), 4.37 (m,
DMSO-d6, ppm) d 7.49 (t, J 7.2 Hz, 1H, H-arom), 7.48 (d, J 8.0 Hz, 1H,
H-arom), 7.36 (t, J 7.2 Hz, 2H, H-arom), 7.29 (d, J 7.2 Hz,1H, H-arom),
6.70 (d, J 16.0 Hz, 1H, Ar–CH]CH–), 6.13 (dd, J 16.0, 6.4 Hz, 1H, Ar–
CH]CH), 4.55 (d, J 6.4 Hz, 1H, OH), 4.49 (d, J 5.6 Hz, 1H, OH), 4.45
(m, 1H, OH), 4.35 (m, 1H, OH), 4.21 (d, J2,CH 7.2 Hz, H-2), 4.13 (m, 1H,
0
0
0
0
2H, OH), 4.37 (m,1H, H-5), 3.78 (t, J1 ,OH¼J1 ,5 6.4 Hz, J1 ,2 0 Hz,1H, H-
10), 3.61 (m, 1H, H-40), 3.53 (m, 1H, H-30), 3.42 (m, 1H, H-400), 3.40
(m, 1H, H-20), 3.29 (t, J4a,4b¼J4a,5 7.2 Hz, 1H, H-4a), 2.54 (t, J4a,4b¼J4b,5
9.2 Hz, 1H, H-4b), 2.10 (s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6,
H-5), 3.64 (t, J1 ,OH¼J1 ,5 5.6 Hz, J1 ,2 0 Hz, 1H, H-10), 3.59 (m, 1H, H-
0
0
0
0
40), 3.48 (m, 1H, H-30), 3.40 (dt, J4 ,OH¼J4 ,3 5.2 Hz, J4 ,4 10.8 Hz, 1H,
00
00
0
00
0
ppm) d 134.04, 131.73, 129.68, 128.74, 126.86, 126.13, 125.52, 125.45
(C-arom), 96.90 (C-2), 78.37 (C-5), 71.39, 71.33 (C-10, C-20, C-30),
63.75 (C-40), 57.38 (C-4), 38.03 (CH3–N).
H-400), 3.23 (dd, J4a,4b 9.0 Hz, J4a,5 6.1 Hz, 1H, H-4a), 3.19 (t,
J2 ,3 ¼J2 ,OH 8.0 Hz, 1H, H-20), 2.28 (t, J4a,4b¼J4b,5 9.6 Hz, 1H, H-4b),
0
0
0
2.21 (s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6, ppm)
d 136.34–
4.2.12.2. Spectroscopic data for compound 8. 1H NMR (400 MHz,
127.11 (C-arom), 97.43 (C-2), 78.91 (C-5), 71.59 (C-10, C-20, C-30),
63.88 (C-40), 57.11 (C-4), 37.99 (CH3).
DMSO-d6, ppm)
d 8.39 (d, J 8.0 Hz, 1H, H-arom), 7.93 (m, 2H, H-
arom), 7.78 (d, J 7.2 Hz, 1H, H-arom), 7.51 (m, 3H, H-arom), 5.48 (s,
1H, H-2), 4.46 (d, J 7.0 Hz,1H, OH), 4.40 (m, 2H, OH), 4.36 (d, J 3.6 Hz,
4.2.14.2. Spectroscopic data for compound 13. 1H NMR (400 MHz,
DMSO-d6, ppm) d 7.49 (t, J 7.2 Hz, 1H, H-arom), 7.48 (d, J 8.0 Hz, 1H,
H-arom), 7.36 (t, J 7.2 Hz, 2H, H-arom), 7.27 (d, J 7.2 Hz,1H, H-arom),
6.71 (d, J 16.0 Hz, 1H, Ar–CH]CH–), 6.14 (dd, J 16.0, 6.0 Hz, 1H, Ar–
CH]CH), 4.55 (d, J 6.4 Hz, 1H, OH), 4.49 (d, J 5.6 Hz, 1H, OH), 4.45
(m, 1H, OH), 4.35 (m, 1H, OH), 4.30 (d, J2,CH 7.2 Hz, 1H, H-2), 4.13 (m,
0
0
1H, OH), 4.28 (q, J4a,5¼J4b,5¼J5,1 6.8 Hz, 1H, H-5), 3.78 (m, 1H, H-1 ),
3.61 (m, 1H, H-40), 3.53 (m, 1H, H-30), 3.42 (m, 1H, H-400), 3.40 (m,
1H, H-20), 3.14 (dd, J4a,4b 10.0 Hz, J4a,5 5.6 Hz, 1H, H-4A), 2.85 (t,
J4a,4b¼J4b,5 8.8 Hz, 1H, H-4b), 2.27 (s, 3H, CH3). 13C NMR (100 MHz,
DMSO-d6, ppm)
d 134.53, 133.88, 131.90, 129.33, 126.31, 125.67,
125.60, 125.00 (C-arom), 96.11 (C-2), 77.85 (C-5), 71.45, 71.18 (C-10,
C-20, C-30), 63.60 (C-40), 53.59 (C-4), 39.36 (CH3–N).
1H, H-5), 3.70 (t, J1 ,OH¼J1 ,5 6.4 Hz, J1 ,2 0 Hz, 1H, H-10), 3.59 (m, 1H,
0
0
0
0
H-40), 3.48 (m, 1H, H-30), 3.40 (dt, J4 ,OH¼J4 ,3 5.2 Hz, J4 ,4 10.8 Hz,
00
00
0
00
0
1H, H-400), 3.19 (t, J2 ,3 ¼J2 ,OH 8.0 Hz, 1H, H-20), 3.07 (dd, J4a,4b 9.8 Hz,
0
0
0
4.2.13. (2R,5S)-3-Methyl-2-(2-hydroxyphenyl)-5-(D-arabino-
1,2,3,4-tetrahydroxybutyl)oxazolidine (9), (2S,5S)-
J4a,5 4.4 Hz, 1H, H-4a), 2.60 (t, J4a,4b¼J4b,5 8.4 Hz, 1H, H-4b), 2.26 (s,
3H, CH3). 13C NMR (100 MHz, DMSO-d6, ppm)
d 136.34–127.11 (C-
3-methyl-2-(2-hydroxyphenyl)-5-(
tetrahydroxybutyl)oxazolidine (10), and (2R,5R)-5-
hydroxy-3-methyl-2-(2-hydroxyphenyl)-5-( -erythro-
1,2,3-trihydroxypropyl)tetrahydro-1,3-oxazine (11)
D
-arabino-1,2,3,4-
arom), 98.09 (C-2), 77.76 (C-5), 71.50, 71.35, 71.24 (C-10, C-20, C-30),
64.03 (C-40), 55.41 (C-4), 38.77 (CH3).
D
4.2.14.3. Spectroscopic data for compound 14. 1H NMR (400 MHz,
Method A (61%); method B (95%); ratio 40:35:25 (9/10/11).
DMSO-d6, ppm) d 7.51–7.27 (m, 5H, H-arom), 6.74 (d, J 16.0 Hz, 1H,
Ar–CH]CH–), 6.25 (dd, J 16.0, 6.0 Hz, 1H, Ar–CH]CH), 4.96 (d, J
4.8 Hz, 1H, OH-5), 4.70 (d, J 4.8 Hz, 1H, OH), 4.26 (d, J2,CH 6.4 Hz, 1H,
H-2), 4.13 (m, 1H, H-6), 3.70 (m, 1H, H-5), 3.71–3.05 (m, 4H, H-10, H-
20, H-30, H-300), 2.93 (dd, J4a,4b 13.2 Hz, J4a,5 2.0 Hz, 1H, H-4a), 2.60
(m, 1H, H-4b), 2.21 (s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6, ppm)
4.2.13.1. Spectroscopic data for compound 9. 1H NMR (400 MHz,
DMSO-d6, ppm)
d 10.71 (br s, 1H, OH-arom), 7.20 (m, 1H, H-arom),
6.76 (m, 3H, H-arom), 4.85 (s, 1H, H-2), 4.21 (m, 1H, H-5), 3.67 (m,
1H, H-10), 3.60 (m, 1H, H-40), 3.56 (m, 1H, 30), 3.48 (m, 1H, H-400),
0
0
3.39 (dd, J4a,4b 9.2 Hz, J4a,5 6.4 Hz, 1H, H-4a), 3.36 (d, J2 ,3 6.4 Hz, 1H,
d 136.34–127.11 (C-arom), 94.83 (C-2), 77.62 (C-6), 74.00 (C-5),
H-20), 2.40 (t, J4a,4b¼J4b,5 9.2 Hz, 1H, H-4b), 2.20 (s, 3H, CH3). 13C
70.86, 66.92 (C-10, C-20), 63.23 (C-30), 60.36 (C-4), 39.77 (CH3).
NMR (100 MHz, DMSO-d6, ppm)
d 157.82–116.03 (C-arom), 95.77
(C-2), 79.32 (C-5), 71.59, 71.56, 71.46 (C-10, C-20, C-30), 63.83 (C-40),
56.49 (C-4), 37.51 (CH3).
1H NMR data refer to the sample exchanged with D2O.
y

R.F. Mart´ınez et al. / Tetrahedron 64 (2008) 6377–6386
6385
4.2.15. 1,4-Bis[(2R,5S)-3-methyl-5-(
tetrahydroxybutyl)oxazolidin-2-yl]benzene (15), 1,4-bis[(2S,5S)-
3-methyl-5-( -arabino-1,2,3,4-tetrahydroxybutyl)oxazolidin-2-
yl]benzene (16), and 1,4-bis[(2R,5R)-5-hydroxy-3-methyl-5-
-erythro-1,2,3-trihydroxypropyl)tetrahydro-1,3-oxazin-2-
D
-arabino-1,2,3,4-
(dd, J4b,4a 10.4 Hz, J4b,5 8.0 Hz, 1H, H-4b), 2.23 (s, 3H, CH3), 2.02,
2.04, 2.06, 2.09 (s, 12H, CH3CO). 13C NMR (100 MHz, CDCl3, ppm)
D
d 170.60, 170.35, 170.06, 169.90 (C]O), 148.48, 145.59, 129.04,
123.42 (C-arom), 98.04 (C-2), 75.43 (C-5), 70.91, 69.16, 68.01 (C-10,
C-20, C-30), 61.73 (C-40), 56.43 (C-4), 38.12 (CH3), 20.93, 20.82, 20.74
(CH3CO). Anal. Calcd for C22H28N2O11: C, 53.22; H, 5.68; N, 5.64.
Found: C, 52.82; H, 5.88; N, 5.76.
(D
yl]benzene (17)
Only compound 15 could be obtained using method A in 51%
yield. Method B, however, affords a mixture of 15–17 (66:22:12) in
87% yield. Recrystallization of this crude mixture from ethanol gave
rise to pure 15 (57% global yield).
4.2.16.2. Spectroscopic data for compound 18. This substance could
not be isolated, although its characterization was carried out by
NMR analysis of the crude mixture: 1H NMR (400 MHz, CDCl3, ppm)
4.2.15.1. Data for compound 15. Method A (51%); method B (57%);
d 8.24 (d, J 8.4 Hz, 2H, H-arom), 7.62 (d, J 8.8 Hz, 2H, H-arom), 5.41
23
mp 128–130 ꢁC; [
a]
þ10 (c 0.5, pyridine); nmax/cmꢀ1 3400–3200
(dd, J2 ,1 2.2 Hz, J2 ,3 9.0 Hz, 1H, H-20), 5.32 (dd, J1 ,2 2.4 Hz, J1 ,5
0
0
0
0
0
0
0
D
(OH), 1632, 1463 (arom), 1073, 1025 (C–O). 1H NMR (400 MHz,
6.0 Hz, 1H, H-10), 5.17 (m, 1H, H-30), 4.77 (s, 1H, H-2), 4.38 (dt,
J5,4a¼J5,1 6.4 Hz, J5,4b 8.8 Hz, 1H, H-5), 4.26 (m, 1H, H-40), 4.18 (dd,
0
DMSO-d6, ppm)
d
7.42 (s, 2H, H-arom), 4.57 (d, J 6.4 Hz, 1H, OH),
J4 ,4 12.8 Hz, J4 ,3 4.4 Hz, 1H, H-400), 3.48 (dd, J4a,4b 9.6 Hz, J4a,5
6.0 Hz, 1H, H-4a), 2.50 (t, J4b,4a¼J4b,5 9.2 Hz, 1H, H-4b), 2.26 (s, 3H,
CH3), 2.14, 2.12, 2.08, 2.08 (s, 12H, CH3CO). 13C NMR (100 MHz,
00
0
00
4.56 (s, 1H, H-2), 4.50 (d, J 6.0 Hz, 1H, OH), 4.35 (t, J 6.2 Hz, 1H, OH),
0
0
4.32 (d, J 7.6 Hz, 1H, OH), 4.26 (m, 1H, H-5), 3.67 (t, J1 ,5¼J1 ,OH 6.4 Hz,
J1 ,2 0 Hz, 1H, H-10), 3.58 (m, J4 ,4 8.8 Hz, J4 ,OH 5.4 Hz, J4 ,3 3.4 Hz,
0
0
0
00
0
0
0
1H, H-40), 3.48 (m, J3 ,2 8.4 Hz, J3 ,OH 5.4 Hz, J3 ,4 3.0 Hz, 1H, H-30),
CDCl3, ppm) d 170.57, 170.49, 169.97, 169.85 (C]O), 148.50, 145.45,
0
0
0
0
0
3.38 (dt, J4 ,OH¼J4 ,3 6.8 Hz, 1H, H-400), 3.32 (dd, J4a,4b 8.8 Hz, J4a,5
128.78,123.56 (C-arom), 96.69 (C-2), 76.05 (C-5), 70.23, 68.69, 68.11
(C-10, C-20, C-30), 61.73 (C-40), 57.17 (C-4), 37.64 (CH3), 20.89, 20.85,
20.78 (CH3CO).
00
00
0
6.4 Hz, 1H, H-4a), 3.20 (t, J2 ,3 ¼J2 ,OH 7.6 Hz, 1H, H-20), 2.35 (t,
0
0
0
J4b,4a¼J4b,5 9.2 Hz, 1H, H-4b), 2.10 (s, 3H, CH3). 13C NMR (100 MHz,
DMSO-d6, ppm) d 139.79 (2C, arom), 127.64 (4C, C-arom), 96.95 (C-
2), 78.78 (C-5), 71.05, 71.02, 70.96 (C-10, C-20, C-30), 63.32 (C-40),
56.81 (C-4), 37.24 (CH3). Anal. Calcd for C22H36N2O10$1⁄2 H2O: C,
52.17; H, 7.30; N, 5.79. Found: C, 52.36; H, 7.18; N, 5.67.
Acknowledgements
This work was supported by the Ministry of Education and
Science (Spain, Grants CTQ2005-07676 and CTQ2007-66641) co-
financed with the Fondo Europeo de Desarrollo Regional (FEDER).
4.2.15.2. Spectroscopy data for compound 16. 1H NMR (400 MHz,
DMSO-d6, ppm)
d 7.36 (s, 4H, H-arom), 4.70 (s, 1H, H-2), 4.18 (dt,
One of us (R.F.M.) thanks the Junta de Extremadura for
scholarship.
a
0
0
0
0
0
J4a,5 4.4 Hz, J4b,5¼J5,1 7.6 Hz, 1H, H-5), 3.66 (t, J1 ,5¼J1 ,OH 6.4 Hz, J1 ,2
0 Hz, 1H, H-10), 3.66–3.30 (m, 3H, H-30, H-40, H-400), 3.20 (t,
J2 ,3 ¼J2 ,OH 7.6 Hz,1H, H-20), 3.08 (dd, J4a,4b 9.2 Hz, J4a,5 4.0 Hz,1H, H-
0
0
0
4a), 2.65 (t, J4b,4a¼J4b,5 8.0 Hz, 1H, H-4b), 2.16 (s, 3H, CH3). 13C NMR
Supplementary data
(100 MHz, DMSO-d6, ppm) d 139.77 (2C, arom),128.41 (4C, C-arom),
Copies of 1H and 13C NMR spectra for all new compounds; Fig-
ures 1S, 2S, and 3S, and Chart 1; Cartesian coordinates of com-
pounds 9–11, 18, and 19. Supplementary data associated with this
article can be found in the online version, at doi:10.1016/
j.tet.2008.04.082.
98.26 (C-2), 77.88 (C-5), 71.05, 71.02, 70.96 (C-10, C-20, C-30), 64.01
(C-40), 55.77 (C-4), 38.57 (CH3).
4.2.15.3. Spectroscopy data for compound 17. 1H NMR (400 MHz,
DMSO-d6, ppm) d 7.47 (d, J 6.8 Hz, 2H, H-arom), 7.42 (d, J 6.8 Hz, 2H,
H-arom), 5.00 (d, J 4.8 Hz, 1H, OH-5), 4.59 (s, 1H, H-2), 4.26 (m, 1H,
H-6), 3.74 (m, 1H, H-5), 3.67–3.30 (m, 4H, H-10, H-20, H-30, H-300),
3.00 (d, J4a,4b 11.2 Hz, 1H, H-4a), 2.68 (d, J4b,4a 11.2 Hz, 1H, H-4b),
References and notes
2.09 (s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6, ppm)
d 128.01 (4C,
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arom), 127.94 (2C, arom), 95.75 (C-2), 78.34 (C-6), 73.94 (C-5),
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4.2.16. (2R,5S)-3-Methyl-2-(4-nitrophenyl)-5-(1,2,3,4-tetra-O-
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(2S,5S)-3-methyl-2-(4-nitrophenyl)-5-(1,2,3,4-tetra-O-acetyl-D-
arabino-1,2,3,4-tetrahydroxybutyl)oxazolidine (19)
To a suspension of the oxazolidine 6a (5.0 mmol) in pyridine
(6.7 mL) was added acetic anhydride (6.5 mL). The mixture was
kept at room temperature overnight and then evaporated. The
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22
Mp 119–120 ꢁC; [
a
]
þ23 (c 0.5, chloroform); nmax/cmꢀ1 1746
D
¨ ¨
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(C]O), 1605, 1529, 1462 (arom), 1247, 1230 (C–O–C, ester), 1078,
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0
H-arom), 7.69 (d, J 8.4 Hz, 2H, H-arom), 5.43 (dd, J2 ,1 2.0 Hz, J2 ,3
d 8.22 (d, J 8.8 Hz, 2H,
´
´
´
Neuvonen, K.; Bernath, G.; Argay, G.; Kalman, A. J. Org. Chem. 1993, 58,
0
0
0
1967.
9.0 Hz, 1H, H-20), 5.34 (dd, J1 ,2 2.0 Hz, J1 ,5 6.4 Hz, 1H, H-10), 5.16
0
0
0
´
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0
0
0
00
0
0
2), 4.24 (m, 1H, H-5), 4.23 (m, 1H, H-40), 4.17 (dd, J4 ,4 12.8 Hz, J4 ,3
4.4 Hz, 1H, H-400), 3.24 (dd, J4a,4b 10.4 Hz, J4a,5 3.2 Hz, 1H, H-4a), 2.76
00
0
00
´
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P212121, a¼7.44300(10) Å, b¼15.7931(2) Å, c¼20.6396(3) Å, V¼2426.15(6) Å3,
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Z¼4, F(000)¼1048, absorption coefficient 0.110 mmꢀ1
,
Dc¼1.359 Mg mꢀ3
, q
range (3.03ꢀ27.48ꢁ). Crystal data for compound 19 have been deposited with
the Cambridge Crystallographic Data Centre (CCDC-665884) and can be
obtained, upon request, from the Director, Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2 1EZ, UK.
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