Synthesis of 2-amino glycal derivatives and their conversion into highly functionalised ss-enamino ketones

Article abstract of DOI:10.1002/ejoc.201000325

A general method for the synthesis of 2-amino glycals employing 2-amino sugar derivatives as precursors is described. A new 2-(amino-disubstituted) glycal backbone is obtained independently of the aglycon and nitrogen substituents, the configuration of th

Full text of DOI:10.1002/ejoc.201000325

FULL PAPER
DOI: 10.1002/ejoc.201000325
Synthesis of 2-Amino glycal Derivatives and their Conversion into Highly
Functionalised β-Enamino Ketones
Fernando Iglesias-Guerra,*[a] Ignacio Periñán,[a] Margarita Vega-Holm,[a] and
José M. Vega-Pérez*[a]
Keywords: Synthetic methods / Carbohydrates / Glycosides / Glycals / Amines / Ketones
A general method for the synthesis of 2-amino glycals em-
ploying 2-amino sugar derivatives as precursors is described.
A new 2-(amino-disubstituted) glycal backbone is obtained
independently of the aglycon and nitrogen substituents, the
configuration of the C-1, C-2 and C-3 atoms of the starting
amino sugar and the oxidative system employed. The reac-
tivity of these new 2-amino glycals with amines has been
studied. The reactions were performed with two differently
N-substituted amino glycals and a variety of alkyl- and aryl-
amines. Highly functionalised β-enamino ketones were ob-
tained by this method.
sides,[16] glycopeptides[17] and α,β-unsaturated lactones.[18]
Different researchers have studied the preparation of glycal
and 2-hydroxy glycal derivatives[19] as well as their reactivity
in cyclopropanation, epoxidation, hydroboration and halo-
fluorination reactions.[20] 3-Amino glycal derivatives have
been used as precursors of glycosidic moieties of antitu-
mour compounds.[21]
Introduction
In the overwhelming majority of cases, carbohydrates
found in nature do not occur in a free form but are linked
to each other or to other types of compound (aglycones)
through glycosidic bonds. Compounds possessing O-, S- or
N-glycosidic linkages occur in nature.[1] Glycosidation reac-
tions play a central role in carbohydrate chemistry for several
reasons. The rapidly growing interest in the biological roles
of glycoconjugates (glycoproteins, glycolipids and proteogly-
cans)[2] requires homogeneous materials to study. On other
hand, carbohydrates, which contain several functional
groups and stereogenic centres in one molecular unit, are
important as tools in stereochemical differentiation, as start-
ing materials in the synthesis of interesting enantiopure com-
pounds,[3] as chiral templates in asymmetric transforma-
tions[4] and as chiral auxiliaries in stereoselective synthesis.[5]
In this sense we have used amino sugars as chiral templates
in the stereoselective synthesis of diamino sugars,[6] chiral
oxazolidines,[7] chiral oxiranes,[8] chiral cyclopropanes[9] and
compounds with potential anticancer activity.[10]
However, antecedents for the synthesis of 2-amino glycal
derivatives are scarce and tend to be non-general pro-
cedures.[22] With regard to the development of suitable
methods for the synthesis of a variety of 2-amino glycals,
we reported for the first time a good general procedure for
the synthesis of 2-[(acyl)(alkyl)amino]-1,5-anhydro-4,6-O-
(R)-benzylidene-2-deoxy-erythro-hex-1-en-3-uloses of type
1
[23] by an oxidative reaction of a variety of 2-[(acyl)(alkyl)-
amino] and 2-(dialkylamino) sugars. The initial work was
aimed at demonstrating the simplicity and effectiveness of
the method, which produced good chemical yields without
the formation of by-products. Two general procedures for
the preparation of 2-amino glycals have since been de-
scribed: one uses glycosyl sulfoxides (obtained from the cor-
responding thioglycosides) as substrates for a β-elimination
reaction in which 2-substituted glycals (2-hydroxy and 2-
amino derivatives) are synthesised[24] and the other employs
selenoglycosides as precursors for an oxidation that pro-
duces anomeric selenoxides, which, by a spontaneous in situ
syn elimination, yield the desired 2-substituted (protected 2-
hydroxy and 2-amino) glycals.[25] In both cases, these com-
pounds have the general structure 2, compounds different
to ours in which the presence of the carbonyl group at C-3
powers their chemical reactivity and versatility.
Glycal derivatives play an important role in carbohydrate
chemistry as precursor compounds in the stereoselective
synthesis of O-glycosides,[11] oligosaccharides,[12] S-glyco-
sides,[13] 2-deoxynucleosides,[14] C-glycosides,[15] C-nucleo-
[a] Departamento de Química Orgánica y Farmacéutica, Facultad
de Farmacia, Universidad de Sevilla,
C/ Profesor García Gonzalez 2, 41012 Sevilla, Spain
E-mail: iglesias@us.es
vega@us.es
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201000325.
Eur. J. Org. Chem. 2010, 4253–4265
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F. Iglesias-Guerra, I. Periñán, M. Vega-Holm, J. M. Vega-Pérez
FULL PAPER
precursors that will be subjected to this oxidation reaction.
We distinguish two different simple synthetic routes that are
widely used in monosaccharide chemistry and furnish good
chemical yields. The aim was to prepare a range of structur-
ally related 2-amino sugar precursors that differ in the na-
ture of both the aglycon and the substituents on the nitro-
gen at C-2 and in the configuration of C-1, C-2 and C-3 (α
or β anomers, gluco, allo or altro configurations) for subjec-
tion to two different oxidative reactions.
In this article we present our efforts to improve our
method, applying it to a variety of 2-[(acyl)(alkyl)amino]
and 2-(dialkylamino) sugar precursors to demonstrate its
versatility. The 2-amino glycals obtained do not depend on
the nature of the aglycon, the substituents on the nitrogen
or the configuration of the C-1, C-2 and C-3 atoms of the
sugar residue. The 2-[(N,N-disubstituted)amino]-1,5-anhy-
dro-4,6-O-benzylidene-2-deoxy-erythro-hex-1-en-3-uloses
obtained were subjected to a simple reaction with different
primary and secondary amines to obtain, in good chemical
yields, β-enamino ketones 3 with an additional nitrogenated
function at the 2-position [dialkylamino or (acyl)(alkyl)-
amino].
The gluco and allo compounds 14–20 (Scheme 1) were
obtained from the corresponding alkyl 2-(acylamino)-4,6-
O-(R)-benzylidene-2-deoxy--hexopyranosides 7–13 by re-
action with LiAlH4, yielding substrates with different sub-
stituents on the nitrogen at the 2-position of the sugar. Sub-
sequent acetylation followed by treatment with sodium
methoxide in methanol yielded the first group of com-
pounds [an (acyl)(alkyl)amino group at the 2-position of
the sugar and OH at the 3-position], which were used to
obtain the new 2-amino glycals.
Compounds of this kind, with the general structure of
enediamino ketones 4 (R = alkyl, aryl), have been prepared
previously by reactions between α-halogenated β-keto ace-
tals and secondary amines.[26] However, we synthesised the
enediamino ketones from 2-amino glycals as precursors so
that the stereochemistry of the sugar moiety as well as its
functionality are present in these compounds.
During the preparation of this manuscript, a paper was
published describing the Michael addition of amines to hex-
1-en-3-uloses (5) to give β-enamino ketones diastereoselec-
tively[27]. The subsequent hydrodeamination reaction per-
formed by hydrogenation on a palladium catalyst generated
the corresponding 1,2-dideoxy--threo-3-hexulose deriva-
tives, which can be used as precursors for the synthesis of
a β-mannosidase inhibitor.
Scheme 1. Reagents and conditions: (i) 1. LiAlH4, THF, reflux; 2.
Ac2O, Py; 3. MeONa, MeOH, 63–76%.
Compounds with the general structure 6 with an altro
configuration were obtained regio- and stereoselectively
(NMR spectroscopic data) from the corresponding methyl
2,3-anhydro-4,6-O-(R)-benzylidene-α--allopyranoside (21)
by an oxirane ring-opening reaction with various primary
and secondary amines.[28] By using a primary amine, the
products 22–24 were obtained. These were acetylated to
give 25–27 and subsequent treatment with sodium meth-
oxide yielded the products 28–30. Ring-opening of the oxir-
ane 21 with a secondary amine gave compound 31 directly,
which was subsequently subjected to oxidation (Scheme 2).
The N,N-disubstituted amino sugars synthesised were
subjected to two different oxidative reactions. Compounds
Results and Discussion
As the general method for obtaining the new 2-amino 14, 15 and 28–30 were oxidised with PCC to give the prod-
glycals involves the oxidation of N,N-disubstituted 2-amino ucts 32–34 in good yields and without the formation of by-
sugar derivatives 6, first we describe the preparation of the products (Scheme 3).
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Synthesis and Reactions of 2-Amino glycal Derivatives
Oxidation of compounds 16–20 by this method gave low
yields because of the usual work-up conditions (low solubil-
ity of the reaction product in diethyl ether), therefore we
subjected these compounds to oxidation by the second oxi-
dative system. Thus, compounds 16–20 were oxidised ef-
ficiently with the DMSO/DCC system to give compounds
35 and 36 (Scheme 4).
Scheme 4. Reagents and conditions: (i) DMSO, molecular
sieves (3 Å), DCC, 75–86%.
Scheme 2. Reagents and conditions: (i) amine, LiClO4, MeCN, re-
flux, 89–96%; (ii) Ac2O, Py, 79–86%; (iii) MeONa, MeOH, 72–
90%.
The oxidation of 16 and 17 (benzyl α- and β--gluco-
pyranoside derivatives), 18 (benzyl β--allopyranoside de-
rivative) and 20 (dodecyl β--glucopyranoside derivative),
all with the same substitution on the nitrogen atom, by this
procedure yielded compound 35 in yields of 75, 77, 77 and
80%, respectively. Finally, compound 19, which possesses a
different alkyl group on the nitrogen atom, was oxidised by
this method and compound 36 was obtained in a yield of
86% (Scheme 4).
The two oxidation reactions yielded the same type of
product, 2-[(acyl)(alkyl)amino]-1,5-anhydro-4,6-O-(R)-benz-
ylidene-2-deoxy-erythro-hex-1-en-3-ulose with a different
N-alkyl group in 2-position of the sugar precursor. Both
reactions took place by oxidation at the 3-position to give
a keto function and elimination of the alkoxide at the an-
omeric position.
Scheme 3. Reagents and conditions: (i) PCC, molecular sieves
(3 Å), CH2Cl2, 67–87%.
To verify the generality of this method for the synthesis
Compounds 14, 15 (benzyl α- and β--glucopyranoside of 2-amino glycals and the independence of the oxidative
derivatives) and 28 (methyl α--altropyranoside derivative), system used, we also oxidised compounds 14, 15 and 28 by
with the same substituents on the nitrogen atom, were oxi- using the second oxidative procedure (DMSO/DCC) and
dised by using the PCC/DCM system (Scheme 3) to give the compound 32 was again obtained in good yields of 88, 91
product 32 in similar yields of 80, 84 and 84%, respectively. and 90%, respectively.
The substrates 29 and 30 (methyl α--altropyranoside de-
The results of these oxidation reactions for the different
rivatives) were oxidised efficiently to give the products 33 compounds studied (Table 1) indicate that the preparation
and 34, which have a similar general structure to 32 but of the 2-amino glycal derivatives is independent of the na-
with different alkyl groups on the nitrogen atom (cyclo- ture of the aglycon and nitrogen substituents and the con-
hexylmethyl and dodecyl, respectively), in yields of 67 and figuration at C-1, C-2 and C-3 of the starting material and
87%, respectively (Scheme 3).
reveal the general character of the procedure.
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F. Iglesias-Guerra, I. Periñán, M. Vega-Holm, J. M. Vega-Pérez
FULL PAPER
Table 1. Yields of the products from the oxidation of the (acyl)-
(alkyl)amino sugar derivatives.
Entry
SM[a]
Configuration[b] Oxidative
system[c]
Product Yield
[%]
1
2
3
4
5
6
7
8
14
15
28
14
15
28
29
30
16
17
18
20
19
benzyl α-gluco
benzyl β-gluco
methyl α-altro
benzyl α-gluco
benzyl β-gluco
methyl α-altro
methyl α-altro
methyl α-altro
benzyl α-gluco
benzyl β-gluco
benzyl β-allo
A
A
A
B
B
B
A
A
B
B
B
B
B
32
32
32
32
32
32
33
34
35
35
35
35
36
80
84
84
88
91
90
67
87
75
77
77
80
86
9
10
11
12
13
dodecyl β-gluco
benzyl α-gluco
[a] Starting material. [b] Configuration of the sugar moiety. [c] Oxi-
dative system employed: (A) PCC/CH2Cl2; (B) DMSO/DCC.
Oxidation of compound 31 with the second oxidising
system (DMSO/DCC) gave 2-(dialkylamino)-1,5-anhydro-
4,6-O-(R)-benzylidene-2-deoxy-erythro-hex-1-en-3-ulose
(37) in good yield (Scheme 5).
Scheme 6. Reagents and conditions: (i) amine, EtOH, r.t., 61–80%.
To determine the configurations of compounds 38–50 we
analysed their NMR spectra. It has previously been re-
ported that the NMR spectra of β-enamino ketones exhibit
NH signals in the low-field region, which suggests strong
hydrogen-bonding between the amino group and the car-
bonyl oxygen atom and that they have a cis structure.[29] In
relation to the configurations of the compounds obtained
from the reactions between glycals and amines, another
group recently postulated the formation of an intramolecu-
lar hydrogen bond between the hydrogen atom of the added
amine and the carbonyl at the 3-position of the β-enamino
ketone finally obtained to explain the postulated geome-
try.[27] The signal arising from the amino proton at C-1 ap-
pears at higher chemical shifts (δ ≈ 10 ppm).
Scheme 5. Reagents and conditions: (i) DMSO, molecular
sieves (3 Å), DCC, 72%.
1
The H NMR spectra of the N,N-disubstituted 2-amino-
1,5-anhydro-4,6-O-(R)-benzylidene-2-deoxy-erythro-hex-1-
en-3-uloses 32–37 exhibit the signal from the proton at the
1-position of the sugar at around 7.0–8.0 ppm. The 13C
NMR spectra exhibit the signal due to C-2 at around
120 ppm and the signal arising from C-1 at around
160 ppm.
Having obtained the new 2-amino glycals, the next step
was to study their reactivity towards amines. As substrates
In our case, compounds 44–49 (with a morpholino group
for the reactions with amines, two types of precursor at the 2-position) were obtained as a mixture of diastereo-
were chosen: 2-(acetyl-benzylamino)-1,5-anhydro-4,6-O- isomers with the diastereoselectivity favouring the Z config-
(R)-benzylidene-2-deoxy--erythro-hex-1-en-3-ulose
(32) uration (Z/E ratio between 2.1–3.5). All the minor stereo-
and 1,5-anhydro-4,6-O-(R)-benzylidene-2-deoxy-2-morph- isomers exhibit the signal arising from the NH at the 1-
olino--erythro-hex-1-en-3-ulose (37). Both compounds re- position at around δ = 9.5–9.7 ppm (COSY experiments),
acted with several primary and secondary amines to give which has been attributed to an intramolecular hydrogen
the β-enamino ketones 38–43 and 44–50, respectively bond as previously mentioned, and a doublet resonance for
(Scheme 6). The reactions were clean, smooth and fast the alkene proton at C-1 at δ = 7.1–7.2 ppm. Thus, we ten-
(20 min from 32 and 2 h from 37) and they appeared to tatively assigned the E configuration to these minor stereo-
occur by nucleophilic addition at C-1 concomitant with isomers. However, for the major stereoisomers, the signal
pyranose ring-opening with no intermediary products being from NH at the 1-position appears at lower chemical shifts
detected.[27]
(δ = 6.4–6.6 ppm, COSY experiments) and the signal from
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Synthesis and Reactions of 2-Amino glycal Derivatives
the alkene proton at the 1-position is at δ = 7.6–7.7 ppm. Table 3. 13C NMR spectroscopic data for the characteristic carbons
in compounds 44–50.[a]
For these stereoisomers, therefore, the Z configuration was
tentatively assigned.
Entry Cp
δ [ppm]
C-3
C-4
C-5
C-6
PhCH
(M)/(m) (M)/(m) (M)/(m) (M)/(m) (M)/(m)
1
2
3
4
5
6
7
44
45
186.4/
191.1
186.7/
191.4
187.8/
192.8
189.7/
192.3
187.9/
192.2
187.4/
192.4
189.9
79.9/
78.5
80.2/
78.5
81.0/
79.5
81.3/
79.4
81.9/
79.5
79.9/
78.5
80.2
61.2/
60.2
61.2/
60.2
61.9/
61.2
62.3/
61.2
62.5/
61.2
61.0/
60.2
61.2
70.5/
70.6
70.5/
70.7
71.4/
71.6
71.4/
71.6
71.6/
71.4
70.5/
70.6
70.4
99.7/
99.9
99.7/
100.0
100.6/
100.9
100.6/
100.9
100.6/
100.9
99.7/
100.0
99.7
46
47
48
To prove this assignment we performed two-dimensional
NMR experiments. The NOESY spectrum of compound 44
shows, for the minor stereoisomer, a correlation between
the alkene proton at the 1-position and the protons of both
CH2 groups next to the nitrogen in the morpholine ring.
This allowed us to confirm its E configuration. However,
this correlation is not present in the major stereoisomer, in
accord with a Z configuration (Figure 1). These data are in
agreement with the results of the NMR studies described
above.
49
50[b]
[a] (M) for the major and (m) for the minor stereoisomer. [b] One
stereoisomer observed.
more so when the amine added has a bulky group (iPr and
tBu; compounds 47 and 48, Table 4, entries 7 and 8, respec-
tively).
Table 4. Z/E ratio for compounds 38–42 and 44–50.[a]
Entry
Compound
Z/E ratio
1
2
3
4
5
6
7
8
9
10
38
39
13.3/1
9.5/1
11.5/1
3.1:1
2.7:1
3.0:1
2.2:1
2.1:1
3.5:1
1.0:0
42
Figure 1. E/Z configurations for compound 44 showing the corre-
lations observed by NOESY experiments for the E configuration.
44
45
For compound 50 only one stereoisomer was obtained.
The chemical shifts and profiles of the signals of the pro-
tons and carbon atoms of this compound are analogous to
those of the major isomers of compounds 44–49. Thus, in
the same way, the Z configuration was tentatively assigned.
See Tables 2 and 3 for the 1H and 13C NMR chemical shifts
of compounds 44–50.
46
47
48
49
50[b]
[a] The ratio was determined by direct 1H NMR examination of
the diastereoisomeric mixture. [b] Tentative assignment.
1
A similar 1H NMR analysis was performed on com-
pounds 38–43, obtained from the reactions between com-
pound 32 and different amines. In all cases we observed
double signals despite recording the spectra at 110 °C. We
think that this is because we have not reached a high
enough temperature for the signals to collapse to single
ones and so the spectra still show a mixture of conformers.
Indeed, both signals have very similar chemical shifts (see
Table 5); in fact, the differences in the chemical shifts are
smaller than the differences observed for the diastereoiso-
meric mixtures obtained from product 37 with different
amines.
Table 2. H NMR spectroscopic data for the characteristic protons
in compounds 44–50.[a]
Entry
Cp
δ [ppm]
N–H
(M)/(m)
1-H
(M)/(m)
4-H
(M)/(m)
PhCH
(M)/(m)
1
2
3
4
5
6
7
44
45
6.58/9.56
6.67/9.78
6.87/9.99
6.41/9.73
6.38/10.0
6.67/9.58
–
7.55/7.11
7.58/7.16
7.62/7.06
7.56/7.14
7.73/7.31
7.55/7.09
7.24
4.38/4.87
4.36/4.87
4.30/4.82
4.30/4.80
4.41/4.91
4.36/4.89
4.41
5.60/5.53
5.61/5.53
5.51/5.45
5.55/5.45
5.67/5.56
5.58/5.54
5.62
46
47
48
49
50[b]
Because the 1H NMR spectra recorded at 110 °C present
unresolved signals due to being close to the coalescence
temperature, the NMR spectroscopic data presented are
[a] (M) for the major and (m) for the minor stereoisomer. [b] One
stereoisomer observed.
Based on these results we believe that for these substrates those recorded at 90 °C in [D6]DMSO with a similar signal
there is a preference for the Z geometry. The proportion of pattern.
the E geometry is increased when the amine added can form
A further two-dimensional NMR analysis was per-
an intramolecular hydrogen bridge with the carbonyl oxy- formed on compound 38, by way of ROESY experiments.
gen at the 3-position (primary amines; 44–49) and even A correlation between the methyl group of the amine at
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1
Table 5. H NMR spectroscopic data for the characteristic protons reactions gave high yields. This methodology is an effective
in compounds 38–43.
way of obtaining new β-enamino ketones that have a poten-
tially modifiable chemical structure.
Entry
Cp
δ [ppm]
Based on the NMR studies of these compounds with an
amide function at the 2-position, the β-enamino ketones
were obtained in high diastereoisomeric excesses with the
major stereoisomer assigned the Z configuration.
The products in which the nitrogen at the 2-position of
the glycal (the nitrogenated function borne on the amino
sugar precursor) forms part of a morpholine ring were ob-
tained as a mixture of Z/E diastereoisomers. The pro-
portion of the Z stereoisomer is slightly higher and was the
only product obtained in the reaction of this glycal with
morpholine as the nucleophilic amine.
N–H
1-H
4-H
PhCH
1
2
3
4
5
6
38
39
40
41
42
43
6.51
6.01
8.66
–
6.86
–
7.61/7.64
7.71/7.74
8.14/8.19
7.53/7.57
7.69/7.72
7.55/7.57
4.42
5.58/5.59
5.64/5.65
5.69/5.71
5.63/5.65
5.55/5.56
5.64/5.65
4.42/4.46
4.61/4.66
4.51/4.52
4.41
4.85/4.88
C-1 and the methyl of the acetamide function at C-2 was
observed. The Z configuration was assigned to this com-
pound (Figure 2).
Given that we have just described the synthesis of glycals
and their reactions with different amines using methods
that are simple and, above all, general, our next aim is to
determine the relationship between the substituents on both
the nitrogen atom at the 2-position of the glycal precursor
and the amine added and the diastereoselectivity of the ad-
dition reaction. Further studies on this topic are in progress.
Figure 2. Correlation detected for compound 38 by ROESY experi-
ments.
Also, for compounds 38, 39 and 42, the small signal ob-
served at 9–10 ppm was attributed to NH, which forms an
intramolecular hydrogen bond with the carbonyl group at
the 3-position[27,29] and, as we previously explained, this is
in accord with the presence of the E stereoisomer. The dia-
stereoisomeric excesses (determined by direct H NMR ex-
amination of the two NH signals at 6–7 and 10 ppm) are
86, 81 and 84%, respectively.
According to these results and based on the fact that the
chemical shifts and profiles of the signals of the protons
and carbon atoms of these compounds are analogous to
those of the major isomer in compounds 44–49, the Z con-
figuration was also tentatively assigned to the major stereo-
isomer of compounds 38–43.
Experimental Section
General Methods: All chemicals were purchased and used without
further purification. Evaporations were conducted under reduced
pressure. Preparative chromatography was performed on silica gel
60 (E. Merck). Kieselgel 60 F254 (E. Merck) was used for TLC.
Optical rotations were determined with a Bellingham + Stanley P-
20 polarimeter at 25 °C. Mass spectra were recorded with a Micro-
mass AUTOSPECQ mass spectrometer at 70 eV for EI and at
150 eV for CI; HRMS measurements were made with resolutions
of 10000. FAB mass spectra were recorded by using a thioglycerol
matrix. NMR spectra were recorded with a Bruker AC-200 spec-
trometer at 200 MHz for 1H NMR and 50 MHz for 13C NMR and
1
1
with a Bruker AV500 spectrometer at 500 MHz for H NMR and
125 MHz for 13C NMR. The chemical shifts are reported in ppm
on the δ scale relative to TMS. DEPT, COSY, HSQC, NOESY and
ROESY experiments were performed to assign the NMR signals
and the configurations of the products from the reactions of the
glycals with amines.
Conclusions
In this work we have presented an effective, simple and
general method for obtaining 2-amino glycals from N,N-
disubstituted 2-amino sugars. We have demonstrated that
obtaining these new 2-amino glycal derivatives does not de-
pend on the nature of the aglycon or the substituents on
the nitrogen atom, the configuration of C-1, C-2 and C-3
of the carbohydrate precursors, or the oxidative procedure
employed. Thus, a range of differently substituted glycals
has been obtained.
Given the importance of glycals as synthetic intermediar-
ies of diverse biologically active compounds, in this work
we have begun the study of the reactivity of new glycals
obtained with different amines. The reactions took place
cleanly to give new β-enamino ketones (with an additional
amine function). We carried out these reactions with two
different glycal precursors (with an amide or amine func-
tion at the 2-position of the glycal) and with different pri-
Synthesis of Alkyl 2-(Acetyl-alkylamino)-4,6-O-(R)-benzylidene-2-
deoxy-D-hexopyranosides 14–20: A solution of alkyl 2-acylamino-
4,6-O-(R)-benzylidene-2-deoxy-β--glucopyranoside
(7–13;
10.0 mmol) in distilled and dry THF (200 mL) was stirred under
argon at reflux. A 1  solution of LiAlH4 in THF (15 mmol) was
added and the reaction mixture was stirred at reflux overnight and
then left to cool to room temperature. A saturated aqueous sodium
sulfate solution (4.5 mL) was added dropwise. The solid was re-
moved by filtration and washed with anhydrous THF. The filtrate
was concentrated to dryness to give a solid, which was recrystal-
lised from 96% ethanol. These compounds were characterised by
mass and NMR analyses and used in the following reactions.
A solution of alkyl 2-(alkylamino)-4,6-O-(R)-benzylidene-2-deoxy-
-hexopyranoside (10.0 mmol) was acetylated in the usual way with
acetic anhydride in pyridine (1:1; 20 mL). The reaction mixture was
kept for 2 d at room temperature and then poured into ice/water
and the precipitate obtained was isolated by filtration. The solid
was dissolved in methanol (50 mL) and a solution of sodium meth-
mary and secondary alkyl- or arylamines. In all cases, the oxide (1.0 mmol) in methanol (10 mL) was added. After 30 min at
4258
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 4253–4265

Synthesis and Reactions of 2-Amino glycal Derivatives
room temperature, the mixture was neutralised by the addition of
Dowex 50 resin (H+ form), filtered and the solvents evaporated to
dryness. The compound obtained was purified by recrystallisation
from 96% ethanol or by column chromatography.
5.0 Hz, 5-H), 4.2–4.3 (m, 3 H, 2-H, 3-H, 6e-H), 4.59 (d, Jgem =
12.0 Hz, OCHAHBPh), 4.80 (d, Jgem = 12.0 Hz, OCHAHBPh), 5.27
(d, J3,OH = 8.0 Hz, OH), 4.75 (d, J1,2 = 8.5 Hz, 1 H, 1-H), 5.64 (s,
1 H, PhCH), 7.2–7.5 (m, 10 H, 2 Ph) ppm. 13C NMR (50 MHz,
[D6]DMSO, 25 °C):
δ = 13.9, 15.2 (NCH2CH3), 21.3, 22.4
Benzyl 2-(Acetyl-benzylamino)-4,6-O-(R)-benzylidene-2-deoxy-α-
glucopyranoside (14): Yield 3.6 g (75%); m.p. 70–71 °C. [α]D
D-
=
(CH3CON), 38.4 (NCH2CH3), 60.5 (C-2), 63.0, 63.1 (C-5), 68.3 (C-
6), 68.9, 69.8 (C-3), 70.0 (OCH2Ph), 78.8, 78.9 (C-4), 97.3, 97.4 (C-
1), 100.5, 100.6 (PhCH), 126.0–137.7 (2 Ph), 170.2, 171.0
(C=O) ppm. C24H29NO6 (427.49): calcd. C 67.43, H 6.84, N 3.28;
found C 67.32, H 6.90, N 3.25.
+103.0 (c = 1.2, CH2Cl2). 1H NMR (200 MHz, [D6]DMSO,
100 °C): δ = 1.98 (s, 3 H, CH3), 5.07 (d, J1,2 = 3.4 Hz, 1 H, 1-H),
5.60 (s, 1 H, PhCH), 7.0–7.5 (m, 15 H, 3 Ph) ppm. 13C NMR
(50 MHz, [D6]DMSO, 25 °C): δ = 22.3, 22.4 (CH3), 45.9, 48.1
(NCH2Ph), 57.4 (C-2), 62.2, 62.9 (C-5), 65.4, 65.6 (C-3), 67.9 (C-
6), 68.8, 69.2 (OCH2Ph), 82.3, 82.6 (C-4), 97.9, 98.6 (C-1), 100.7,
100.8 (PhCH), 125.7–139.9 (3 Ph), 171.7, 172.5 (C=O) ppm. MS
(CI): m/z (%) = 490 (100) [M]+·. HRMS (CI): calcd. For
C29H32NO6 [M + H]+ 490.222963; found 490.222753. C29H31NO6
(489.56): calcd. C 71.15, H 6.38, N 2.86; found C 70.98, H 6.12, N
2.81.
Benzyl 2-(Acetyl-methylamino)-4,6-O-(R)-benzylidene-2-deoxy-α-
glucopyranoside (19): Yield 3.1 g (76%); m.p. 89–91 °C. [α]D
D-
=
+111.8 (c = 1.2, CH2Cl2). 1H NMR (200 MHz, [D6]DMSO, 25 °C):
δ = 1.99, 2.04 (2 s, 3 H, CH3CON), 2.83, 2.97 (2 s, 3 H, NCH3),
4.3–4.7 (m, 3 H, OCH2Ph, 6e-H), 4.80, 5.11 (2 d, J1,2 = 3.3, 3.5 Hz,
1-H), 5.42, 5.52 (2 d, J3,OH = 6.3, 5.9 Hz, OH), 5.63 (s, 1 H, PhCH),
7.3–7.5 (m, 10 H, 2 Ph) ppm. 13C NMR (50 MHz, [D6]DMSO,
25 °C): δ = 21.8, 22.2 (CH3CON), 28.8, 32.0 (NCH3), 56.9, 61.5
(C-2), 62.9, 63.1 (C-5), 65.0, 65.5 (C-3), 67.9 (C-6), 68.7, 69.0
(OCH2Ph), 81.9, 82.3 (C-4), 97.7, 98.9 (C-1), 100.8 (PhCH), 126.4–
137.7 (2 Ph), 170.5, 171.0 (C=O) ppm. MS (CI): m/z (%) = 414 (50)
[M + H]+. HRMS (CI): calcd. for C23H28NO6 [M + H]+
414.191663; found 414.189950. C23H27NO6 (413.46): calcd. C
66.81, H 6.58, N 3.39; found C 66.66, H 6.85, N 3.17.
Benzyl 2-(Acetyl-benzylamino)-4,6-O-(R)-benzylidene-2-deoxy-β-D-
glucopyranoside (15): Yield 3.5 g (72%); m.p. 64–65 °C. [α]D = –68.6
1
(c = 1.8, CH2Cl2). H NMR (200 MHz, [D6]DMSO, 110 °C): δ =
2.05 (s, 3 H, CH3), 4.63 (d, J1,2 = 8.3 Hz, 1 H, 1-H), 5.59 (s, 1 H,
PhCH), 7.1–7.5 (m, 15 H, 3 Ph) ppm. 13C NMR (50 MHz, [D6]-
DMSO, 25 °C): δ = 22.3 (CH3), 44.3 (NCH2Ph), 65.1, 65.2 (C-2,
C-5), 67.7 (C-3), 67.9 (C-6), 70.0 (OCH2Ph), 81.4 (C-4), 99.3 (C-
1), 100.7 (PhCH), 126.2–139.5 (3 Ph), 171.7 (C=O) ppm. MS (CI):
m/z (%) = 490 (100) [M]+·. HRMS (CI): calcd. for C29H32NO6 [M
+ H]+ 490.222963; found 490.222427. C29H31NO6 (489.56): calcd.
C 71.15, H 6.38, N 2.86; found C 71.37, H 6.35, N 3.00.
1-Dodecyl 2-(Acetyl-ethylamino)-4,6-O-(R)-benzylidene-2-deoxy-β-
D
-glucopyranoside (20): Yield 3.1 g (63%). 1H NMR (200 MHz,
[D6]DMSO, 90 °C): δ = 0.88 (t, J = 6.7 Hz, 3 H, CH3), 1.12 (m, 3
H, NCH2CH3), 1.3–1.6 [m, 20 H, (CH2)10], 2.01 (s, 3 H, CH3CON),
4.69 (d, J1,2 = 8.2 Hz, 1 H, 1-H), 5.58 (s, 1 H, PhCH), 7.3–7.5 (m,
5 H, Ph) ppm. 13C NMR (50 MHz, [D6]DMSO, 25 °C): δ = 13.8,
14.0 (2 CH3), 22.1 (CH3CON), 22.2–29.0 [(CH2)10], 36.2
(NCH2CH3), 64.9, 65.1 (C-2, C-5), 67.8 (C-3), 67.9 (C-6), 68.9
(OCH2Ph), 81.7, 82.0 (C-4), 99.7 (C-1), 100.7 (PhCH), 126.3–137.7
(Ph), 170.6 (C=O) ppm. MS (CI): m/z (%) = 506 (100) [M + H]+.
HRMS (CI): calcd. for C29H48NO6 [M + H]+ 506.348164; found
506.347411.
Benzyl 2-(Acetyl-ethylamino)-4,6-O-(R)-benzylidene-2-deoxy-α-
glucopyranoside (16): Yield 3.2 g (76%); m.p. 67–68 °C. [α]D
D-
=
+124.3 (c = 1.6, CH2Cl2). 1H NMR (200 MHz, [D6]DMSO,
100 °C): δ = 0.98, 1.12 (2 t, J = 7.0, 6.8 Hz, 3 H, NCH2CH3), 2.02,
2.04 (2 s, 3 H, CH3CON), 4.4–4.7 (m, 3 H, OCH2Ph, 6e-H), 4.78,
5.09 (2 d, J1,2 = 3.3, 3.6 Hz, 1-H), 5.41, 5.51 (2 d, J3,OH = 6.1,
5.9 Hz, OH), 5.63 (s, 1 H, PhCH), 7.5–7.2 (m, 10 H, 2 Ph) ppm.
13C NMR (50 MHz, [D6]DMSO, 25 °C):
δ = 13.7, 15.1
(NCH2CH3), 21.5, 22.3 (CH3CON), 37.7, 39.5 (NCH2CH3), 57.4,
62.1 (C-2), 62.7 (C-5), 65.4, 65.8 (C-3), 67.9 (C-6), 68.9, 69.1
(OCH2Ph), 82.4, 82.8 (C-4), 97.4, 98.8 (C-1), 100.9 (PhCH), 126.4–
137.7 (2 Ph), 170.6, 171.2 (C=O) ppm. MS (CI): m/z (%) = 428
(100) [M + H]+. C24H29NO6 (427.49): calcd. C 67.43, H 6.84, N
3.28; found C 67.66, H 6.85, N 3.17.
Synthesis of Methyl 2-(Alkylamino)-4,6-O-(R)-benzylidene-2-deoxy-
α-D-altropyranosides 22–24, 31: A solution of the oxirane
(10 mmol) and LiClO4 (20 mmol) in MeCN (40 mL) was heated
whilst stirring at 90 °C and the corresponding amine (40 mmol)
was added. The mixture was stirred until completion of the reaction
(TLC). It was then left to cool to room temperature and poured
into ice/water with stirring. In most cases, the precipitate obtained
was filtered off and crystallised from EtOH or EtOH/water. In
some cases, when the reaction mixture was soluble in ice/water, the
aqueous solution was extracted with CH2C12 and the combined
extracts were washed with water. The organic phase was dried
(Na2SO4) and evaporated in vacuo to dryness. The solid obtained
was crystallised or fractionated by chromatography on a silica gel
column.
Benzyl 2-(Acetyl-ethylamino)-4,6-O-(R)-benzylidene-2-deoxy-β-D-
glucopyranoside (17): Yield 2.9 g (70%); m.p. 60–61 °C. [α]D = –74.3
1
(c = 1.2, CH2Cl2). H NMR (200 MHz, [D6]DMSO, 100 °C): δ =
1.09 (t, J = 7.0 Hz, 3 H, NCH2CH3), 1.99 (s, 3 H, CH3CON), 3.2–
3.6 (m, 6 H, 2-H, 3-H, 4-H, 5-H, NCH2CH3), 3.75 (t, J5,6a = J6e,6a
= 10.0 Hz, 1 H, 6a-H), 4.2–4.3 (m, 2 H, 1-H, 6e-H), 4.55 (d, Jgem
= 12.1 Hz, OCHAHBPh), 4.78 (d, Jgem = 12.1 Hz, OCHAHBPh),
5.59 (s, 1 H, PhCH), 7.2–7.5 (m, 10 H, 2 Ph) ppm. 13C NMR
(50 MHz, [D6]DMSO, 25 °C):
δ = 13.9 (NCH2CH3), 22.2
(CH3CON), 36.2 (NCH2CH3), 64.9, 65.2 (C-2, C-5), 67.8 (C-3),
67.9 (C-6), 70.3 (OCH2Ph), 81.6, 81.9 (C-4), 99.2 (C-1), 100.7
(PhCH), 126.3–137.8 (2 Ph), 170.6 (C=O) ppm. MS (CI): m/z (%)
= 428 (100) [M + H]+. C24H29NO6 (427.49): calcd. C 67.43, H 6.84,
N 3.28; found C 67.68, H 6.84, N 3.14.
Methyl 2-(Benzylamino)-4,6-O-(R)-benzylidene-2-deoxy-α-D-altro-
pyranoside (22): Yield 3.5 g (95%); m.p. 164–165 °C. [α]D = +43.0
(c = 0.7, CH2Cl2). 1H NMR (200 MHz, [D6]DMSO, 25 °C): δ =
2.75 (d, J2,3 = 2.0 Hz, 1 H, 2-H), 3.36 (s, 3 H, OCH3), 3.65–3.75
(m, 3 H, NCH2Ph, 6a-H), 3.9–4.1 (m, 3 H, 3-H, 4-H, 5-H), 4.20
(dd, J5,6e = 4.8, J6a,6e = 9.7 Hz, 1 H, 6e-H), 4.50 (d, J3,OH = 5.0 Hz,
OH), 4.59 (s, 1 H, 1-H), 5.64 (s, 1 H, PhCH), 7.2–7.5 (m, 10 H, 2
Ph) ppm. 13C NMR (50 MHz, [D6]DMSO, 25 °C) δ = 51.3
Benzyl 2-(Acetyl-ethylamino)-4,6-O-(R)-benzylidene-2-deoxy-β-D-
allopyranoside (18): Yield 2.8 g (67%); m.p. 59–60 °C. [α]D = –44.1
(c = 1.0, CH2Cl2). MS (CI): m/z (%) = 428 (100) [M + H]+. 1H
NMR (200 MHz, [D6]DMSO, 100 °C): δ = 1.12 (t, J = 7.0 Hz, 3 (NCH2Ph), 51.3 (OCH3), 57.7 (C-5), 60.7 (C-2), 66.9 (C-3), 68.5
H, NCH2CH3), 2.03 (s, 3 H, CH3CON), 3.45 (m, 2 H, NCH2CH3), (C-6), 76.4 (C-4), 100.5 (C-1), 101.1 (PhCH), 126.4–140.6 (2
3.7–3.8 (m, 2 H, 4-H, 6a-H), 4.03 (dt, J4,5 = J5,6a = 9.8, J5,6e
=
Ph) ppm. MS (CI): m/z (%) = 372 (100) [M + H]+. C21H25NO5
Eur. J. Org. Chem. 2010, 4253–4265
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4259

F. Iglesias-Guerra, I. Periñán, M. Vega-Holm, J. M. Vega-Pérez
FULL PAPER
(371.43): calcd. C 67.91, H 6.78, N 3.77; found C 67.66, H 6.93, N
3.53.
50.0 (NCH2Ph), 55.0 (OCH3), 57.9, 58.4, 60.0 (C-2, C-5), 68.3 (C-
6), 67.7, 69.1 (C-3), 73.0, 73.8 (C-4), 98.4 (C-1), 100.8 (PhCH),
125.8–138.5 (2 Ph), 169.0, 169.9, 171.3 (2C=O) ppm. MS (CI): m/z
(%) = 456 (100) [M + H]+. C25H29NO7 (455.50): calcd. C 65.92, H
6.42, N 3.08; found C 66.18, H 6.68, N 2.90.
Methyl
oxy-α-
4,6-O-(R)-Benzylidene-2-[(cyclohexylmethyl)amino]-2-de-
-altropyranoside (23): Yield 3.5 g (96%); m.p. 123–125 °C.
D
[α]D = +36.9 (c = 1.7, CH2Cl2). 1H NMR (200 MHz, CDCl3,
25 °C): δ = 0.8–1.8 (m, 11 H, c-C6H11), 2.49 (m, 2 H, NCH2R),
2.97 (d, J2,3 = 2.4 Hz, 1 H, 2-H), 3.41 (s, 3 H, OCH3), 3.7–3.9 (m,
2 H, 4-H, 6a-H), 4.1–4.4 (m, 3 H, 3-H, 5-H, 6e-H), 4.61 (s, 1 H, 1-
H), 5.61 (s, 1 H, PhCH), 7.5–7.3 (m, 5 H, Ph) ppm. 13C NMR
(50 MHz, CDCl3, 25 °C) δ = 25.9–31.3 [(CH2)5], 38.0 (CH), 55.3
(NCH2R), 55.5 (OCH3), 58.4 (C-5), 60.9 (C-2), 68.5 (C-3), 69.2 (C-
6), 76.9 (C-4), 101.5 (C-1), 102.2 (PhCH), 126.2–137.3 (Ph) ppm.
MS (CI): m/z (%) = 378 (85) [M + H]+. HRMS (EI): calcd. for
C21H31NO5 [M]+· 377.220223; found 377.219005. C21H31NO5
(377.47): calcd. C 66.82, H 8.28, N 3.71; found C 66.84, H 8.23, N
3.75.
Methyl
benzylidene--2-deoxy-α-
3-O-Acetyl-2-[acetyl(methylcyclohexyl)amino]-4,6-O-(R)-
-altropyranoside (26): Yield 3.6 g (79%);
D
m.p. 152–154 °C. [α]D = +28.2 (c = 1.7, CH2Cl2). 1H NMR
(200 MHz, [D6]DMSO, 80 °C): δ = 0.9–1.8 (m, 11 H, c-C6H11),
2.03, 2.05 (2 s, 6 H, 2 CH3CO), 3.15 (m, 2 H, NCH2R), 3.33 (s, 3
H, OCH3), 3.54 (dd, J1,2 = 4.5, J2,3 = 3.5 Hz, 1 H, 2-H), 3.73 (t,
J5,6a = J6a,6e = 10.0 Hz, 1 H, 6a-H), 3.98 (dt, J4,5 = J5,6a = 10.0,
J5,6e = 5.0 Hz, 1 H, 5-H), 4.7–4.9 (m, 2 H, 4-H, 6e-H), 4.92 (d, J1,2
= 4.7 Hz, 1 H, 1-H), 5.47 (dd, J2,3 = 3.6, J3,4 = 4.5 Hz, 1 H, 3-H),
5.65 (s, 1 H, PhCH), 7.3–7.4 (m, 5 H, Ph) ppm. 13C NMR
(50 MHz, [D6]DMSO, 25 °C): δ = 20.7, 22.3 (2 CH3CO), 25.7–30.2
[(CH2)5], 37.0 (CH), 55.4 (OCH3), 56.7 (NCH2R), 60.0 (C-5), 63.5
(C-2), 68.8 (C-6), 69.0 (C-3), 73.5 (C-4), 98.3 (C-1), 100.1 (PhCH),
126.0–137.7 (Ph) ppm. MS (CI): m/z (%) = 462 (100) [M + H]+.
HRMS (EI): calcd. for C25H35NO7 [M]+· 461.241353; found
461.239426. C25H35NO7 (461.55): calcd. C 65.06, H 7.64, N 3.03;
found C 65.30, H 7.41, N 3.07.
Methyl 4,6-O-(R)-Benzylidene-2-deoxy-2-(1-dodecylamino)-α-
D-al-
tropyranoside (24): Yield 4.2 g (95%); m.p. 136–138 °C. [α]D
=
1
+42.3 (c = 2.1, CH2Cl2). H NMR (200 MHz, CDCl3, 25 °C): δ =
0.86 (t, J = 6.9 Hz, 3 H, CH3), 1.2–1.6 [m, 20 H (CH2)10], 2.65 (t,
2 H, NCH2R), 3.00 (d, J2,3 = 2.8 Hz, 1 H, 2-H), 3.41 (s, 3 H,
OCH3), 3.7–3.9 (m, 2 H, 4-H, 6a-H), 4.07 (t, J2,3 = J3,4 = 2.8 Hz,
1 H, 3-H), 4.15 (m, 1 H, 5-H), 4.30 (m, 1 H, 6e-H), 4.61 (s, 1 H,
1-H), 5.60 (s, 1 H, PhCH), 7.3–7.5 (m, 5 H, Ph) ppm. 13C NMR
(50 MHz, CDCl3, 25 °C): δ = 14.1 (CH3), 22.7–31.9 [(CH2)10], 48.6
(NCH2R), 55.6 (OCH3), 58.5 (C-2), 60.7 (C-5), 68.5 (C-3), 69.2 (C-
6), 76.8 (C-4), 101.4 (C-1), 102.3 (PhCH), 126.2–137.3 (Ph) ppm.
MS (CI): m/z (%) = 450 (100) [M + H]+. HRMS (EI): calcd. for
C26H43NO5 [M]+· 449.314124; found 449.312115. C26H43NO5
(449.62): calcd. C 69.45, H 9.64, N 3.12; found C 69.44, H 9.37, N
2.93.
Methyl
idene-2-deoxy-α-
3-O-Acetyl-2-[acetyl(1-dodecyl)amino]-4,6-O-(R)-benzyl-
-altropyranoside (27): Yield 4.5 g (84%); m.p.
D
1
103–105 °C. [α]D = +48.0 (c = 0.5, CH2Cl2). H NMR (200 MHz,
[D6]DMSO, 100 °C): δ = 0.86 (t, J = 7.0 Hz, 3 H, CH3), 1.2–1.7
[m, 20 H (CH2)10], 2.03, 2.08 (2 s, 6 H, 2 CH3CO), 3.2–3.5 (m, 5
H, NCH2R, OCH3), 3.74 (t, J5,6a = J6a,6e = 9.9 Hz, 1 H, 6a-H, 3.93
(t, J1,2 = J2,3 = 3.3 Hz, 1 H, 2-H), 4.04 (dt, J4,5 = J5,6a = 9.7, J5,6e
= 4.8 Hz, 1 H, 5-H), 4.17 (dd, J3,4 = 4.4, J4,5 = 9.8 Hz, 1 H, 4-H),
4.29 (dd, J5,6e = 4.8, J6a,6e = 9.9 Hz, 1 H, 6e-H), 4.83 (d, J1,2
=
3.3 Hz, 1 H, 1-H), 5.32 (dd, J2,3 = 3.4, J3,4 = 4.3 Hz, 1 H, 3-H),
5.66 (s, 1 H, PhCH), 7.3–7.4 (m, 5 H, Ph) ppm. 13C NMR
(50 MHz, [D6]DMSO, 25 °C): δ = 13.9 (CH3), 20.7, 21.6 (2
CH3CO), 22.1–31.2 [(CH2)10], 43.0, 47.8 (NCH2R), 54.9 (OCH3),
58.5, 58.7 (C-5), 59.3, 59.9 (C-2), 68.5 (C-6), 68.3, 69.4 (C-3), 73.1,
73.8 (C-4), 98.8 (C-1), 100.9 (PhCH), 126.0–137.6 (Ph), 169.2,
170.4 (2 C=O) ppm. MS (CI): m/z (%) = 534 (100) [M + H]+.
C30H47NO7 (533.70): calcd. C 67.51, H 8.88, N 2.62; found C
67.60, H 9.00, N 2.34.
Methyl 4,6-O-(R)-Benzylidene-2-deoxy-2-morpholino-α-D-altropyr-
anoside (31): Yield 3.1 g (89%); m.p. 118–119 °C. [α]D = +71.7 (c
1
= 1.3, CH2Cl2). H NMR (200 MHz, CDCl3, 25 °C): δ = 2.65 (m,
4 H, CH2NCH2), 2.78 (d, J2,3 = 2.3 Hz, 1 H, 2-H), 3.14 (d, J3,OH
= 6.7 Hz, 1 H, OH), 3.40 (s, 3 H, OCH3), 3.68 (t, J = 4.6 Hz, 4 H,
CH2OCH2), 3.78 (t, J5,6a = J6a,6e = 10.0 Hz, 1 H, 6a-H), 3.91 (dd,
J3,4 = 3.1, J4,5 = 9.7 Hz, 1 H, 4-H), 4.1–4.2 (m, 2 H, 3-H, 5-H),
4.31 (dd, J5,6e = 5.0, J6a,6e = 10.0 Hz, 1 H, 6e-H), 4.82 (s, 1 H, 1-
H), 5.63 (s, 1 H, PhCH), 7.3–7.5 (m, 5 H, Ph) ppm. 13C NMR
(50 MHz, CDCl3, 25 °C): δ = 51.2 (CH2NCH2), 55.5 (OCH3), 57.9
(C-2), 66.0 (C-5), 67.0 (C-3), 67.3 (CH2OCH2), 69.3 (C-6), 77.4 (C-
4), 100.0 (C-1), 102.2 (PhCH), 126.2–137.2 (Ph) ppm. MS (CI): m/z
(%) = 352 (100) [M + H]+. C18H25NO6 (351.39): calcd. C 61.52, H
7.17, N 3.99; found C 61.73, H 7.05, N 3.86.
Synthesis of Methyl 2-(Acetyl-alkylamino)-4,6-O-(R)-benzylidene-2-
deoxy-α-D-altropyranosides 28–30: A solution of sodium methoxide
(1.0 mmol) in methanol (10 mL) was added to a solution of methyl
3-O-acetyl-2-(acetyl-alkylamino)-4,6-O-(R)-benzylidene-2-deoxy-α-
-altropyranoside (25–27; 10.0 mmol) in methanol (50 mL). After
50 min at room temperature the mixture was neutralised by ad-
dition of Dowex 50 resin (H+ form), filtered and the solvents evap-
orated to dryness. The compound obtained was purified by
chromatography on a silica gel column.
Synthesis of Methyl 3-O-Acetyl-2-(acetyl-alkylamino)-4,6-O-(R)-
benzylidene-2-deoxy-α-D-altropyranoside (25–27): A solution of
methyl 2-alkylamino-4,6-O-(R)-benzylidene-2-deoxy-α--altropyr-
anoside (22–24; 10.0 mmol) was acetylated in the usual way with
acetic anhydride/pyridine (1:1; 40 mL). The reaction mixture was
kept for 2 d at room temperature and then poured into ice/water.
The precipitate obtained was isolated by filtration. The solid ob-
tained was purified by chromatography on a silica gel column.
Methyl 2-(Acetyl-benzylamino)-4,6-O-(R)-benzylidene-2-deoxy-α-
altropyranoside (28): Yield 3.4 g (83%); m.p. 188–190 °C. [α]D
D-
=
+48.3 (c = 1.2, CH2Cl2). 1H NMR (200 MHz, [D6]DMSO, 110 °C):
δ = 2.09 (s, 3 H, CH3CON), 3.22 (m, 3 H, OCH3), 3.66 (t, J5,6a
=
Methyl 3-O-Acetyl-2-(acetyl-benzylamino)-4,6-O-(R)-benzylidene-2-
J6a,6e = 9.9 Hz, 1 H, 6a-H), 3.75 (dd, J3,4 = 3.7, J4,5 = 9.7 Hz, 1 H,
4-H), 3.98 (t, J2,3 = J3,4 = 3.6 Hz, 1 H, 3-H), 4.07 (m, 1 H, 5-H),
deoxy-α-D-altropyranoside (25): Yield 3.9 g (86%); m.p. 183–
185 °C. [α]D = +33.4 (c = 1.6, CH2Cl2). 1H NMR (200 MHz, [D6]- 4.23 (m, 1 H, 6e-H), 4.35 (t, J1,2 = J2,3 = 3.5 Hz, 1 H, 2-H), 4.71
DMSO, 80 °C): δ = 1.95, 2.12 (2 s, 6 H, 2 CH3CO), 3.29 (m, 3 H,
(d, J1,2 = 3.3 Hz, 1 H, 1-H), 4.80 (m, 2 H, NCH2Ph), 5.47 (s, 1 H,
OCH3), 3.69 (t, J5,6a = J6a,6e = 9.9 Hz, 1 H, 6a-H), 3.95–4.05 (m, 2 PhCH), 7.2–7.5 (m, 10 H, 2 Ph) ppm. 13C NMR (50 MHz, [D6]-
H, 4-H, 5-H), 4.2–4.3 (m, 2 H, 2-H, 6e-H), 4.75 (s, 2 H, NCH2Ph),
4.81 (d, J1,2 = 2.7 Hz, 1 H, 1-H), 5.30 (t, J2,3 = J3,4 = 2.8 Hz, 1 H,
DMSO, 25 °C): δ = 22.0 (CH3CON), 45.9, 49.0 (NCH2Ph), 54.6
(OCH3), 57.4 (C-5), 59.1, 63.0 (C-2), 66.8, 68.1 (C-3), 68.4 (C-6),
3-H), 5.48 (s, 1 H, PhCH), 7.2–7.4 (m, 10 H, 2 Ph) ppm. 13C NMR 75.7, 76.5 (C-4), 98.6, 98.8 (C-1), 100.9 (PhCH), 125.3–139.4 (2
(50 MHz, [D6]DMSO, 25 °C): δ = 20.7, 21.8, 22.0 (2 CH3CO), 45.8, Ph), 170.9, 171.1 (C=O) ppm. MS (CI): m/z (%) = 414 (100) [M +
4260
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 4253–4265

Synthesis and Reactions of 2-Amino glycal Derivatives
H]+. C23H27NO6 (413.46): calcd. C 66.81, H 6.58, N 3.39; found C
66.61, H 6.53, N 3.47.
m.p. 72–74 °C. [α]D = +125.1 (c = 0.3, CH2Cl2). 1H NMR
(200 MHz, [D6]DMSO, 25 °C): δ = 0.8–1.7 (m, 11 H, c-C6H11),
1.76, 1.88 (2 s, 3 H, CH3CON), 2.7–3.6 (4 m, 2 H, NCH2R), 4.10,
4.11 (2 t, J5,6a = J6a,6e = 10.1 Hz, 1 H, 6a-H), 4.46 (dd, J5,6e = 5.1,
J6a,6e = 10.2 Hz, 1 H, 6e-H), 4.69 (m, 1 H, 5-H), 4.94, 4.97 (2 d,
J4,5 = 13.0 Hz, 1 H, 4-H), 5.72, 5.73 (2 s, 1 H, PhCH), 7.3–7.5 (m,
5 H, Ph), 7.96, 8.00 (2 s, 1 H, 1-H) ppm. When the spectrum was
recorded at 90 °C all the double signals collapsed to single signals.
13C NMR (50 MHz, [D6]DMSO, 25 °C): δ = 21.6, 21.8 (CH3CON),
25.3–30.2 [(CH2)5], 35.7 (CH), 51.8, 53.5 (NCH2R), 66.7 (C-6),
72.5, 72.6 (C-5), 75.8 (C-4), 100.6, 100.7 (PhCH), 121.6, 122.1 (C-
2), 126.3–136.8 (Ph), 162.6, 163.2 (C-1), 170.6, 171.1 (CH3CON),
185.8, 186.0 (C-3) ppm. MS (CI): m/z (%) = 386 (100) [M + H]+.
HRMS (EI): calcd. for C22H27NO5 [M]+· 385.188923; found
385.188494. C22H27NO5 (385.45): calcd. C 68.55, H 7.06, N 3.63;
found C 68.51, H 7.23, N 3.50.
Methyl 2-[Acetyl(cyclohexylmethyl)amino]-4,6-O-(R)-benzylidene-2-
deoxy-α-D-altropyranoside (29): Yield 3.8 g (90%); m.p. 54–56 °C.
1
[α]D = +57.2 (c = 0.7, CH2Cl2). H NMR (200 MHz, [D6]DMSO,
80 °C): δ = 0.8–1.9 (m, 11 H, c-C6H11), 2.08 (s, 3 H, CH3CON),
3.2–3.5 (m, 5 H, NCH2R, OCH3), 3.5–3.8 (m, 2 H, 3-H, 6a-H),
4.0–4.2 (m, 2 H, 4-H, 5-H), 4.30 (m, 1 H, 6e-H), 4.50 (br. s, 1 H,
2-H), 4.86 (d, J1,2 = 3.3 Hz, 1 H, 1-H), 5.67 (s, 1 H, PhCH), 7.3–
7.6 (m, 5 H, Ph) ppm. 13C NMR (50 MHz, [D6]DMSO, 25 °C): δ
= 22.4 (CH3CON), 25.7–30.7 [(CH2)5], 36.7, 37.0 (CH), 54.8, 55.3
(OCH3), 49.1, 56.4 (NCH2R), 57.6, 59.1 (C-5), 63.4, 66.3 (C-2),
67.8, 68.3 (C-3), 68.6, 69.0 (C-6), 76.1 (C-4), 98.6, 99.4 (C-1), 100.6,
100.9 (PhCH), 126.5–137.9 (Ph), 170.5, 171.2 (C=O) ppm. MS
(CI): m/z (%) = 420 (100) [M + H]+. HRMS (EI): calcd. for
C23H33NO6 [M]+· 419.230788; found 419.229786. C23H33NO6
(419.51): calcd. C 65.85, H 7.93, N 3.34; found C 65.54, H 7.77, N
3.29.
2-[Acetyl(1-dodecyl)amino]-1,5-anhydro-4,6-O-(R)-benzylidene-2-de-
1
oxy-
D
-erythro-hex-1-en-3-ulose (34): Syrup, yield 0.80 g (87%). H
Methyl 2-[Acetyl(1-dodecyl)amino]-4,6-O-(R)-benzylidene-2-deoxy-
NMR (500 MHz, [D6]DMSO, 25 °C): δ = 0.84 (t, J = 6.9 Hz, 3 H,
CH3), 1.1–1.4 [m, 20 H, (CH2)10], 1.74, 1.86 (2 s, 3 H, CH3CON),
2.9–3.6 (4 m, 2 H, NCH2R), 4.11 (t, J5,6a = J6a,6e = 10.1 Hz, 1 H,
6a-H), 4.46 (dd, J5,6e = 5.2, J6a,6e = 10.2 Hz, 1 H, 6e-H), 4.68 (m,
2-N-α-
D-altropyranoside (30): Yield 3.5 g (72%); m.p. 77–79 °C. [α]
= +232.9 (c = 2.2, CH2Cl2). 1H NMR (200 MHz, [D6]DMSO,
D
100 °C): δ = 0.86 (t, J = 7.0 Hz, 3 H, CH3), 1.2–1.7 [m, 20 H, (CH2)
10], 2.07 (s, 3 H, CH3CON), 3.2–3.5 (m, 5 H, NCH2R, OCH3), 3.71 1 H, 5-H), 4.95 (d, J4,5 = 13.1 Hz, 1 H, 4-H), 5.72, 5.73 (2 s, 1 H,
(t, J5,6a = J6a,6e = 9.9 Hz, 1 H, 6a-H), 4.27 (dd, J5,6e = 4.9, J6a,6e
=
PhCH), 7.3–7.5 (m, 5 H, Ph), 7.95, 7.99 (2 s, 1 H, 1-H) ppm. When
the spectrum was recorded at 110 °C all the double signals col-
10.0 Hz, 1 H, 6e-H), 4.78 (d, J1,2 = 3.4 Hz, 1 H, 1-H), 5.68 (s, 1 H,
PhCH), 7.3–7.5 (m, 5 H, Ph) ppm. 13C NMR (50 MHz, [D6] lapsed to single signals. 13C NMR (50 MHz, [D6]DMSO, 25 °C): δ
DMSO, 25 °C): δ = 13.9 (CH3), 21.6, 22.0 (CH3CON), 22.2–31.2
= 13.9 (CH3), 21.5, 21.7 (CH3CON), 22.1–31.3 [(CH2)10], 46.2, 47.8
[(CH2)10], 43.3, 47.0 (NCH2R), 54.7 (OCH3), 57.3, 57.6 (C-5), 60.9, (NCH2R), 66.7 (C-6), 72.5, 72.6 (C-5), 75.8, 75.9 (C-4), 100.6, 100.7
63.2 (C-2), 67.3, 68.4 (C-3), 68.7 (C-6), 76.1, 76.6 (C-4), 99.2 (C- (PhCH), 121.3, 121.7 (C-2), 126.3–136.7 (Ph), 162.5, 163.0 (C-1),
1), 100.9 (PhCH), 126.4–137.7 (Ph), 170.0 (C=O) ppm. MS (CI):
170.1, 170.6 (CH3CON), 185.8, 186.0 (C-3) ppm. MS (CI): m/z (%)
m/z (%) = 492 (100) [M + H]+. HRMS (CI): calcd. for C28H46NO6 = 458 (100) [M + H]+. HRMS (EI): calcd. for C22H39NO5 [M]+·
[M + H]+ 492.332514; found 492.333125. C28H45NO6 (491.66): 457.282824; found 457.278976.
calcd. C 68.40, H 9.23, N 2.85; found C 68.39, H 9.10, N 2.64.
Procedure B: Dicyclohexylcarbodiimide (8.0 mmol) was added to a
stirred mixture of 2-[(acyl)(alkyl)amino] or 2-(dialkylamino) sugars
Oxidation Reactions
Procedure A: Pyridinium chlorochromate (4 mmol) and molecular
sieves (3 Å, 10 g) were added to a solution of 2-[(acyl)(alkyl)amino]
sugar derivatives 14, 15 and 28–30 (2.0 mmol) in dry dichlorometh-
16–20 (2.0 mmol), molecular sieves (3 Å, 1 g) and anhydrous di-
methyl sulfoxide (30–40 mL) cooled to 0 °C. After 10 min, anhy-
drous orthophosphoric acid (8.4 mmol) was added portionwise
ane (40 mL). The reaction mixture was stirred vigorously overnight with cooling (ice bath) so that the temperature was kept at 25–
at room temperature. After completion of the reaction (TLC), di-
ethyl ether was added and the mixture was filtered through a glass
filter filled with silica gel containing CaSO4 (10%). Removal of the
solvent by evaporation in vacuo gave a pure compound.
30 °C. The reaction mixture was stirred for 24 h at room tempera-
ture. The solids were removed by filtration and washed with di-
methyl sulfoxide and acetone. The solution was diluted with four
volumes of dichloromethane, water was added and then a potas-
sium carbonate solution (2.4 ) was added to bring the aqueous
phase to about pH 8. The aqueous layer was extracted with dichlo-
romethane and the combined extracts were washed with water until
neutral. The organic phase was dried (Na2SO4) and evaporated in
vacuo to dryness. The solid obtained was crystallised or fraction-
ated by chromatography on a silica gel column.
2-N-Acetyl-2-amino-1,5-anhydro-2-N-benzyl-4,6-O-(R)-benzylidene-
2-deoxy-D-erythro-hex-1-en-3-ulose (32): Yield 0.61 g (80%) from
compound 14, 0.64 g (84%) from compound 15 and 0.64 g (84%)
from compound 28; m.p. 78–80 °C. [α]D = +109.0 (c = 0.6,
1
CH2Cl2). H NMR (500 MHz, [D6]DMSO, 25 °C): δ = 1.85, 1.98
(2 s, 3 H, CH3CON), 3.90, 4.00 (2 d, Jgem = 14.6, 14.5 Hz, 1 H,
NCHAHBPh), 4.06 (m, 1 H, 6a-H), 4.41 (m, 1 H, 6e-H), 4.68 (m, 1
H, 5-H), 4.77, 4.94 (2 d, J4,5 = 13.1, 12.7 Hz, 1 H, 4-H), 5.06, 5.11
(2 d, Jgem = 14.7, 14.4 Hz, 1 H, NCHAHBPh), 5.69, 5.71 (2 s, 1 H,
PhCH), 7.3–7.5 (m, 10 H, 2 Ph), 7.59, 7.62 (2 s, 1 H, 1-H) ppm.
When the spectrum was recorded at 110 °C, all the double signals
collapsed to single signals. 13C NMR (50 MHz, [D6]DMSO, 25 °C):
δ = 20.7, 20.9 (CH3CON), 48.6, 50.4, (NCH2Ph), 65.9 (C-6), 71.9
(C-5), 75.1 (C-4), 99.8, 100.0 (PhCH), 120.1, 120.5 (C-2), 126.6–
136.9 (2 Ph), 161.9, 162.3 (C-1), 169.9, 170.4 (CH3CON), 184.8,
185.1 (C-3) ppm. MS (CI): m/z (%) = 380 (100) [M + H]+.
C22H21NO5 (379.41): calcd. C 69.65, H 5.58, N 3.69; found C
69.43, H 5.76, N 3.74.
2-(Acetyl-ethylamino)-1,5-anhydro-4,6-O-(R)-benzylidene-2-deoxy-
D
-erythro-hex-1-en-3-ulose (35): Yield 0.48 g (75 %) from com-
pound 16, 0.59 g (77%) from compound 17, 0.48 g (77%) from
compound 18 and 0.51 g (80%) from compound 20; m.p. 118–
1
119 °C. [α]D = –95.0 (c = 0.5, CH2Cl2). H NMR (500 MHz, [D6]-
DMSO, 25 °C): δ = 1.98 (s, 3 H, CH3CON), 3.23 (t, 3 H,
NCH2CH3), 3.52, 3.58 (2 m, 2 H, NCH2CH3), 4.25 (m, 1 H, 6a-
H), 4.48 (dd, J5,6e = 5.1, J6a,6e = 10.3 Hz, 1 H, 6e-H), 4.54 (m, 1
H, 5-H), 4.75, 4.80 (2 d, J4,5 = 12.1, 12.1 Hz, 1 H, 4-H), 5.51, 5.52
(2 s, 1 H, PhCH), 7.2–7.5 (m, 5 H, Ph), 8.03, 8.06 (2 s, 1 H, 1-
H) ppm. When the spectrum was recorded at 110 °C all the double
signals collapsed to single signals. 13C NMR (50 MHz, [D6]DMSO,
2-[Acetyl(cyclohexylmethyl)amino]-1,5-anhydro-4,6-O-(R)-benzyl- 25 °C): δ = 18.3, 18.5 (NCH2CH3), 21.1, 21.3 (CH3CON), 49.5,
idene-2-deoxy- -erythro-hex-1-en-3-ulose (33): Yield 0.51 g (67%); 50.8 (NCH2CH3), 66.8 (C-6), 72.3, 72.7 (C-5), 75.6 (C-4), 100.0,
D
Eur. J. Org. Chem. 2010, 4253–4265
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4261

F. Iglesias-Guerra, I. Periñán, M. Vega-Holm, J. M. Vega-Pérez
FULL PAPER
100.6 (PhCH), 122.8, 123.0 (C-2), 126.2–142.5 (Ph), 162.1, 162.6 2 H, 6e-H), 4.42, 4.46 (2 d, J4,5 = 9.1 Hz, 1 H, 4-H), 4.79 (m, 1 H,
(C-1), 170.0, 170.9 (CH3CON), 185.4, 185.5 (C-3) ppm. MS (CI): OH), 5.10 (d, Jgem = 13.7 Hz, 1 H, NCHAHBPh), 5.64, 5.65 (2 s, 1
m/z (%) = 318 (50) [M + H]+. HRMS (CI): calcd. for C17H20NO5 H, PhCH), 6.01 (m, 1 H, NH), 7.13–7.43 (m, 10 H, 2 Ph), 7.71,
[M + H]+ 318.1341; found 318.1336.
7.74 (2 d, J1,NH = 9.0 Hz, 1 H, 1-H) ppm. 13C NMR (125 MHz,
[D6]DMSO, 80 °C): δ = 21.0, 21.3 [NC(CH3)3], 29.0, 29.1
(CH3CON), 48.4, 48.9 (NCH2Ph), 51.8, 52.4 [NC(CH3)3], 61.7,
62.0 (C-5), 70.8, 70.9 (C-6), 80.0, 80.7 (C-4), 99.7, 100.2 (PhCH),
112.8, 113.1 (C-2), 125.9–138.0 (Ph), 148.6, 148.7 (C-1), 171.7,
171.9 (CH3CON), 185.6 (C-3) ppm. MS (FAB): m/z (%) = 475
(100) [M + Na]+. C26H32N2O5 (452.54): calcd. C 68.97, H 7.12, N
6.19; found C 68.65, H 7.17, N 5.91.
2-(Acetyl-methylamino)-1,5-anhydro-4,6-O-(R)-benzylidene-2-de-
oxy-D-erythro-hex-1-en-3-ulose (36): Yield 0.52 g (86%); m.p. 140–
142 °C. [α]D = +195.8 (c = 0.5, CH2Cl2). 1H NMR (500 MHz, [D6]-
DMSO, 25 °C): δ = 1.77, 1.88 (2 s, 3 H, CH3CON), 2.84, 2.94 (2
s, 3 H, NCH3), 4.10 (t, J5,6a = J6a,6e = 10.2 Hz, 1 H, 6a-H), 4.45
(dd, J5,6e = 5.1, J6a,6e = 10.3 Hz, 1 H, 6e-H), 4.65 (m, 1 H, 5-H),
4.89, 4.96 (2 d, J4,5 = 13.0, 13.0 Hz, 1 H, 4-H), 5.72, 5.73 (2 s, 1
H, PhCH), 7.3–7.5 (m, 5 H, Ph), 8.03, 8.06 (2 s, 1 H, 1-H) ppm.
When the spectrum was recorded at 110 °C all the double signals
collapsed to single signals. 13C NMR (50 MHz, [D6]DMSO, 25 °C):
δ = 21.2, 21.4 (CH3CON), 34.9, 36.8 (NCH3), 66.6 (C-6), 72.4, 72.8
(C-5), 75.8 (C-4), 100.6 (PhCH), 123.0, 123.5 (C-2), 126.2–142.5
(Ph), 162.2, 162.9 (C-1), 170.0, 170.9 (CH3CON), 185.4, 185.7 (C-
3) ppm. MS (CI): m/z (%) = 304 (100) [M + H]+. C16H17NO5
(303.31): calcd. C 63.36, H 5.65, N 4.62; found C 63.51, H 5.23, N
4.50.
(4R,5R)-2-(Acetyl-benzylamino)-4,6-O-(R)-benzylidene-1-(phenyl-
amino)-4,5,6-trihydroxyhex-1-en-3-one (40): Yield 0.32 g (68%);
m.p. 93–94 °C. [α]D = –73.4 (c = 1.0, CH2Cl2). 1H NMR (500 MHz,
[D6]DMSO, 90 °C): δ = 1.80, 181 (2 s, 3 H, CH3CON), 3.65 (t, J5,6a
= J6a,6e = 10.4 Hz, 1 H, 6a-H), 3.87, 3.94 (2 m, 1 H, 5-H), 4.15–
4.20 (m, 2 H, 6e-H, NCHAHBPh), 4.61, 4.66 (2 d, J4,5 = 9.1, 9.0 Hz,
1 H, 4-H), 4.82, 4.86 (2 m, 1 H, OH), 4.89, 4.90 (2 d, J = 13.8 Hz,
1 H, NCHAHBPh), 5.69, 5.71 (2 s, 1 H, PhCH), 6.9–7.4 (m, 15 H,
3 Ph), 8.14, 8.19 (2 s, 1 H, 1-H), 8.66 (m, 1 H, NH) ppm. MS (EI):
m/z (%) = 472 (50) [M]+·. 1HRMS (EI): calcd. for C28H28N2O5 [M]
+· 472.1998; found 472.2003. C28H28N2O5 (472.53): calcd. C 71.17,
H 5.97, N 5.93; found C 70.87, H 6.01, N 5.77.
1,5-Anhydro-4,6-O-(R)-benzylidene-2-deoxy-2-morpholino-D-
erythro-hex-1-en-3-ulose (37): Yield 0.45 g (72%); m.p. 196–198 °C.
[α]D = +149.1 (c = 0.5, CH2Cl2). 1H NMR (500 MHz, CDCl3,
25 °C): δ = 2.85 (m, 4 H, CH2NCH2), 3.78 (m, 4 H, CH2OCH2),
4.00 (t, J5,6a = J6a,6e = 10.2 Hz, 1 H, 6a-H), 4.31 (m, 1 H, 5-H),
4.4–4.5 (m, 2 H, 4-H, 6e-H), 5.56 (s, 1 H, PhCH), 7.00 (s, 1 H, 1-
H), 7.35–7.55 (m, 5 H, Ph) ppm. 13C NMR (125 MHz, CDCl3,
25 °C): δ = 51.1 (CH2NCH2), 66.9 (CH2OCH2), 68.0 (C-6), 72.4
(C-5), 77.6 (C-4), 102.0 (PhCH), 126.4–136.3 (Ph), 130.8 (C-2),
150.7 (C-1), 185.7 (C-3) ppm. MS (CI): m/z (%) = 318 (100) [M +
H]+. HRMS (CI): calcd. for C21H29N2O6 [M + H]+ 318.1328;
found 318.1336. C17H19NO5 (317.34): calcd. C 64.34, H 6.03, N
4.41; found C 64.57, H 6.23, N 4.46.
(4R,5R)-2-(Acetyl-2-benzylamino)-4,6-O-(R)-benzylidene-1-(diethyl-
amino)-4,5,6-trihydroxyhex-1-en-3-one (41): Obtained as a syrup;
yield 0.31 g (68 %). [α]D = +39.5 (c = 1.0, CH2Cl2). 1H NMR
(500 MHz, [D6]DMSO, 90 °C): δ = 0.88 [t, J = 7.0 Hz, 6 H,
N(CH2CH3)2], 1.81, 183 (2 s, 3 H, CH3CON), 3.00, 3.25 [2 m, 4
H, N(CH2CH3)2], 3.62 (m, 1 H, 6a-H), 3.90 (m, 1 H, 5-H), 4.03,
4.04 (2 d, Jgem = 13.7 Hz, 1 H, NCHAHBPh), 4.19 (dd, J5,6e = 5.4,
J6a,6e = 10.7 Hz, 1 H, 6e-H), 4.51, 4.52 (2 d, J4,5 = 9.0, 8.9 Hz, 1
H, 4-H), 4.81 (m, 1 H, OH), 4.86, 4.92 (2 d, Jgem = 13.7 Hz, 1 H,
NCHAHBPh), 5.63, 5.65 (2 s, 1 H, PhCH), 7.3–7.5 (m, 5 H, Ph),
7.53, 7.57 (2 s, 1 H, 1-H) ppm. 13C NMR (125 MHz, [D6]DMSO,
80 °C): δ = 13.5 [N(CH2CH3)2], 21.3, 21.4 (CH3CON), 49.6, 49.8
[N(CH2CH3)2], 51.1, 51.4 (NCH2Ph), 61.7, 62.0 (C-5), 70.8, 70.9
(C-6), 80.0, 80.5 (C-4), 100.0, 100.1 (PhCH), 112.8, 113.1 (C-2),
125.9–138.0 (Ph), 148.6, 148.7 (C-1), 172.0, 172.1 (CH3CON),
187.8 (C-3) ppm. MS (CI): m/z (%) = 453 (100) [M + H]+. HRMS
(CI): calcd. for C26H33N2O5 [M + H]+ 453.2389; found 453.2379.
C26H32N2O5 (452.54): calcd. C 68.97, H 7.12, N 6.19; found C
68.85, H 7.17, N 5.98.
Reaction of the Amino Glycals with Amines: The corresponding
amine (2.0 mmol) dissolved in ethanol was added to a solution of
compound 32 or 37 (0.38 g, 1.0 mmol) in ethanol (10 mL), and the
solution was kept at room temperature until TLC showed that all
the starting material had reacted (20 min from 32, 2 h from 37).
The solvent was removed by evaporation to dryness and the solid
obtained was purified by flash chromatography.
(4R,5R)-2-(Acetyl-benzylamino)-4,6-O-(R)-benzylidene-1-(methyl-
amino)-4,5,6-trihydroxyhex-1-en-3-one (38): Yield 0.33 g (80 %);
m.p. 86–87 °C. [α]D = –48.7 (c = 0.5, CH2Cl2). 1H NMR (500 MHz,
[D6]DMSO, 90 °C): δ = 1.74, 1.76 (2 s, 3 H, CH3CON), 2.72 (d, J
= 4.9 Hz, 1 H, NCH3), 3.59 (m, 1 H, 6a-H), 3.92 (m, 1 H, 5-H),
4.09, 4.11 (2 d, Jgem = 13.8 Hz, NCHAHBPh), 4.16 (m, 1 H, 6e-H),
4.42 (m, 1 H, 4-H), 4.80, 4.84 (2 m, 1 H, OH), 4.80, 4.84 (2 d, Jgem
= 13.8 Hz, 1 H, NCHAHBPh), 5.58, 5.59 (2 s, 1 H, PhCH), 6.51
(4R,5R)-2-(Acetyl-benzylamino)-4,6-O-(R)-benzylidene-1-[(meth-
oxycarbonylmethyl)amino]-4,5,6-trihydroxyhex-1-en-3-one (42):
Yield 0.29 g (62 %). [α]D = –54.4 (c = 0.5, CH2Cl2). 1H NMR
(500 MHz, [D6]DMSO, 90 °C): δ = 1.81, 182 (2 s, 3 H, CH3CON),
3.56 (m, 1 H, 6a-H), 3.63, 3.64 (2 s, 3 H, NCH2CO2CH3), 3.80–
4.00 (m, 3 H, NCH2Ph, 5-H), 4.16 (m, 1 H, 6e-H), 4.28 (m, 1 H,
NCHAHBCO2CH3), 4.41 (m, 1 H, 4-H), 4.6–4.8 (m, 2 H,
NCHAHBCO2CH3, OH), 5.55, 5.56 (2 s, 1 H, PhCH), 6.86 (m, 1
H, NH), 7.1–7.4 (m, 10 H, 2 Ph), 7.69, 7.72 (2 d, J1,NH = 8.6 Hz,
1 H, 1-H) ppm. 13C NMR (125 MHz, [D6]DMSO, 90 °C): δ = 20.3,
20.5 (CH3CON), 47.9 (NCH2Ph), 49.1, 49.5 (NCH2CO2CH3), 51.3
(NCH2CO2CH3), 61.0 (C-5), 70.5 (C-6), 79.1, 79.5 (C-4), 99.5, 99.6
(PhCH), 115.2 (C-2), 125.7–137.6 (2 Ph), 150.3, 150.5 (C-1), 169.6
(NCH2CO2CH3), 171.1, 171.2 (CH3CON), 186.1 (C-3) ppm. MS
(EI): m/z (%) = 468 (20) [M]+·. HRMS (EI): calcd. for C25H28N2O7
[M]+· 468.1897; found 468.1883. C25H28N2O7 (468.50): calcd. C
64.09, H 6.02, N 5.98; found C 64.32, H 6.15, N 6.12.
(m, 1 H, NH), 7.13–7.42 (m, 10 H, 2 Ph), 7.61, 7.64 (2 d, J1,NH
=
11.6 Hz, 1 H, 1-H) ppm. 13C NMR (125 MHz, [D6]DMSO, 80 °C):
δ = 20.9, 21.1 (CH3CON), 34.4 (NCH3) 48.9, 49.0 (NCH2Ph), 61.1,
61.4 (C-5), 70.7, 70.8 (C-6), 78.6, 79.1 (C-4), 99.7, 99.8 (PhCH),
114.2 (C-2), 126.1–138.0 (Ph), 151.9 (C-1), 171.4, 171.6
(CH3CON), 184.9 (C-3) ppm. MS (CI): m/z (%) = 411 (100) [M +
H]+. C23H26N2O5 (410.46): calcd. C 67.30, H 6.38, N 6.82; found
C 67.52, H 6.45, N 7.12.
(4R,5R)-2-(Acetyl-benzylamino)-4,6-O-(R)-benzylidene-1-[(tert-
butyl)amino]-4,5,6-trihydroxyhex-1-en-3-one (39): Yield 0.33 g
(73%); m.p. 80–82 °C. [α]D = –59.5 (c = 0.5, CH2Cl2). 1H NMR
(500 MHz, [D6]DMSO, 90 °C): δ = 0.97, 0.98 [2 s, 9 H, C(CH3)3],
(4R,5R)-2-(Acetyl-benzylamino)-4,6-O-(R)-benzylidene-1-morphol-
1.75, 1.76 (2 s, 3 H, CH3CON), 3.63 (m, 1 H, 6a-H), 3.79, 3.84 (2 ino-4,5,6-trihydroxyhex-1-en-3-one (43): Obtained as a syrup; yield
d, Jgem = 13.7 Hz, 1 H, NCHAHBPh), 3.95 (m, 1 H, 5-H), 4.20 (m, 0.30 g (64%). [α]D = –74.4 (c = 0.5, CH2Cl2). 1H NMR (500 MHz,
4262
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 4253–4265

Synthesis and Reactions of 2-Amino glycal Derivatives
[D6]DMSO, 90 °C): δ = 1.79, 1.81 (2 s, 3 H, CH3CON), 3.10–3.40 H major), 3.91 (m, 0.25 H, 5-H minor), 4.08 (dd, J5,6e = 5.4, J6a,6e
(m, 8 H, 4 CH2), 3.62 (m, 1 H, 6a-H), 4.87, 4.89 (2 d, J = 13.7,
13.6 Hz, 1 H, NCHAHBPh), 3.98 (m, 1 H, 5-H), 4.20 (dd, J5,6e
5.4, J6a,6e = 10.7 Hz, 1 H, 6e-H), 4.57 (m, 1 H, OH), 4.85, 4.88 (2 9.4 Hz, 0.25 H, 4-H minor), 5.45 (s, 0.33 H, PhCH minor), 5.51 (s,
= 10.6 Hz, 1 H, 6e-H), 4.30 (d, J4,5 = 9.4 Hz, 0.75 H, 4-H major),
=
4.40 (d, 2 H, NCH2Ph), 4.61, 4.68 (2 m, 1 H, OH), 4.82 (d, J4,5
=
d, J4,5 = 5.5, 5.7 Hz, 1 H, 4-H), 4.99, 5.07 (2 d, Jgem = 13.7 Hz, 1
H, NCHAHBPh), 5.64, 5.65 (2 s, 1 H, PhCH), 7.2–7.5 (m, 10 H,
0.75 H, PhCH major), 6.87 (m, 0.75 H, NH major), 7.06 (d, J1,NH
= 12.7 Hz, 0.25 H, 1-H minor), 7.2–7.3 (m, 5 H, Ph), 7.62 (d, J1,NH
Ph), 7.55, 7.57 (2 s, 1 H, 1-H) ppm. 13C NMR (125 MHz, [D6]- = 13.1 Hz, 0.75 H, 1-H major), 9.99 (m, 0.25 H, NH minor) ppm.
DMSO, 90 °C): δ = 20.9, 21.0 (CH3CON), 49.6 (CH2NCH2), 50.1,
50.4 (NCH2Ph), 61.1, 61.4 (C-5), 65.4 (CH2OCH2), 70.4, 70.5 (C-
6), 79.0, 79.2 (C-4), 99.5, 99.6 (PhCH), 112.3, 112.7 (C-2), 125.6–
137.6 (2 Ph), 147.9 (C-1), 171.4, 171.5 (CH3CON), 187.7 (C-
3) ppm. MS (EI): m/z (%) = 466 (70) [M]+·. HRMS (EI): calcd. for
C26H30N2O6 [M]+· 466.2104; found 466.2121.
1 3 C NMR (125 MHz, [D6 ]DMSO, 25 °C): δ = 50.2, 55.0
(CH2NCH2), 54.1 (NCH2Ph) 61.2 (C-5 minor), 61.9 (C-5 major),
67.6, 67.7 (CH2OCH2), 71.4 (C-6 major), 71.6 (C-6 minor), 79.5
(C-4 minor), 81.0 (C-4 major), 100.6 (PhCH major), 100.9 (PhCH
minor), 122.9 (C-2 minor), 123.1 (C-2 major), 126.5–139.3 (Ph),
150.1 (C-1 minor), 150.5 (C-1 major), 187.8 (C-3 major), 192.8 (C-
3 minor) ppm. MS (EI): m/z (%) = 424 (100) [M]+. HRMS (EI):
calcd. for C24H28N2O5 [M]+ 424.1998; found 424.1991.
(4R,5R)-4,6-O-(R)-Benzylidene-1-(methylamino)-2-morpholino-
4,5,6-trihydroxyhex-1-en-3-one (44): The solid compound was ob-
tained as a Z/E mixture in a 3:1 ratio; yield 0.27 g (77%). [α]D
=
(4R,5R)-4,6-O-(R)-Benzylidene-1-(isopropylamino)-2-morpholino-
+131.7 (c = 1.0, CH2Cl2). 1H NMR (500 MHz, [D6]DMSO, 25 °C): 4,5,6-trihydroxyhex-1-en-3-one (47): The syrupy compound was ob-
δ = 2.68, 2.86 (2 m, 4 H, CH2NCH2), 2.97 (d, J = 4.9 Hz, 3 H, tained as a Z/E mixture in a 2.2:1 ratio; yield 0.30 g (80%). [α]D
=
1
NCH3), 3.56–3.62 (m, 5 H, 6a-H, CH2OCH2), 3.90, 3.98 (2 m, 1 –30.4 (c = 0.7, CH2Cl2). H NMR (500 MHz, [D6]DMSO, 25 °C):
H, 5-H), 4.15 (dd, J5,6e = 5.5, J6a,6e = 10.7 Hz, 1 H, 6e-H), 4.38 (d, δ = 1.10, 1.12 (2 d, J = 3.7 Hz, 6 H, 2 CH3), 2.63, 2.83 (2 m, 4 H,
J4,5 = 9.0 Hz, 0.75 H, 4-H major), 4.64 (m, 1 H, OH), 4.87 (d, J4,5 CH2NCH2), 3.52 [m, 6 H, CH2OCH2, 6a-H, NCH(CH3)2], 3.81 (m,
= 9.4 Hz, 0.25 H, 4-H minor), 5.53 (s, 0.25 H, PhCH minor), 5.60
(s, 0.75 H, PhCH major), 6.58 (m, 0.75 H, NH major), 7.11 (s, 0.25
H, 1-H minor), 7.3–7.4 (m, 5 H, Ph), 7.55 (s, 0.75 H, 1-H major),
9.56 (m, 0.25 H, NH minor) ppm. 13C NMR (125 MHz, [D6]-
DMSO, 25 °C): δ = 33.4 (NCH3 major), 33.8 (NCH3 minor), 49.2
0.69 H, 5-H major), 3.90 (m, 0.31 H, 5-H minor), 4.08 (dd, J5,6a =
5.7, J6a,6e = 10.7 Hz, 1 H, 6e-H), 4.30 (d, J4,5 = 9.4 Hz, 0.69 H, 4-
H major), 4.62, 4.69 (2 m, 1 H, OH), 4.80 (d, J4,5 = 9.3 Hz, 0.31
H, 4-H minor), 5.45 (s, 0.31 H, PhCH minor), 5.55 (s, 0.69 H,
PhCH major), 6.41 (m, 0.69 H, NH major), 7.14 (d, J1,NH
=
(CH2NCH2), 61.2 (C-5 major), 60.2 (C-5 minor), 66.7 (CH2OCH2), 13.0 Hz, 0.31 H, 1-H minor), 7.2–7.3 (m, 5 H, Ph), 7.56 (s, J1,NH
70.5 (C-6 major), 70.6 (C-6 minor), 78.5 (C-4 minor), 79.9 (C-4
= 13.0 Hz, 0.69 H, 1-H major), 9.73 (m, 0.31 H, NH minor) ppm.
major), 99.7 (PhCH major), 99.9 (PhCH minor), 121.6 (C-2 13C NMR (125 MHz, [D6]DMSO, 25 °C): δ = 23.7, 23.8 (2 CH3),
minor), 121.8 (C-2 major), 125.6–137.8 (Ph), 151.4 (C-1 major), 48.4, 54.9 (CH2NCH2), 50.5 [NCH(CH3)], 61.2 (C-5 minor), 62.3
151.5 (C-1 minor), 186.4 (C-3 major), 191.1 (C-3 minor) ppm. MS
(EI): m/z (%) = 348 (60) [M]+. HRMS (EI): calcd. for C18H24N2O6
[M]+ 348.1685; found 348.1695. C18H24N2O5 (348.39): calcd. C
62.05, H 6.94, N 8.04; found C 61.89, H 7.10, N 7.88.
(C-5 major), 67.6, 67.8 (CH2OCH2), 71.4 (C-6 major), 71.6 (C-6
minor), 79.4 (C-4 minor), 81.3 (C-4 major), 100.6 (PhCH major),
100.9 (PhCH minor), 122.4 (C-2 minor), 122.7 (C-2 major), 126.5–
139.3 (Ph), 149.0 (C-1), 189.7 (C-3 major), 192.3 (C-3 minor) ppm.
MS (EI): m/z (%) = 376 (100) [M]+. HRMS (EI): calcd. for
C20H28N2O5 [M]+ 376.1998; found 376.1982.
(4R,5R)-1-Amino-4,6-O-(R)-benzylidene-1-N-butyl-2-morpholino-
4,5,6-trihydroxyhex-1-en-3-one (45): The solid compound was ob-
tained as a Z/E mixture in a 2.7:1 ratio; yield 0.27 g (69%). [α]D
=
(4R,5R)-4,6-O-(R)-Benzylidene-1-[(tert-butyl)amino]-2-morpholino-
–125.0 (c = 0.9, CH2Cl2). 1H NMR (500 MHz, [D6]DMSO, 25 °C): 4,5,6-trihydroxyhex-1-en-3-one (48): The syrupy compound was ob-
δ = 0.88 (m, 3 H, CH3), 1.31, 1.50 [2 m, 4 H, (CH2)2], 2.68, 2.86
(2 m, 4 H, CH2NCH2), 3.24 (m, 2 H, NCH2), 3.55–3.64 (m, 5 H,
6a-H, CH2OCH2), 3.90, 3.98 (2 m, 1 H, 5-H), 4.15 (m, 1 H, 6e-H),
4.36 (d, J4,5 = 9.1 Hz, 0.73 H, 4-H major), 4.64, 4.69 (2 m, 1 H,
OH), 4.87 (d, J4,5 = 9.4 Hz, 0.27 H, 4-H minor), 5.53 (s, 0.27 H,
PhCH minor), 5.61 (s, 0.73 H, PhCH major), 6.67 (m, 0.73 H, NH
tained as a Z/E mixture in a 2.1:1 ratio; yield 0.24 g (61%). [α]D =
+124.2 (c = 0.8, CH2Cl2). 1H NMR (500 MHz, [D6]DMSO, 25 °C):
δ = 1.25, 1.29, 1.31 (3 s, 3 CH3), 2.73, 2.89 (2 m, 4 H, CH2NCH2),
3.63 (m, 5 H, CH2OCH2, 6a-H), 3.91 (m, 0.68 H, 5-H major), 4.01
(m, 0.32 H, 5-H minor), 4.19 (dd, J5,6a = 5.5, J6a,6e = 10.6 Hz, 1
H, 6e-H), 4.41 (d, J4,5 = 9.4 Hz, 0.68 H, 4-H major), 4.72, 4.75 (2
major), 7.16 (d, J1,NH = 12.8 Hz, 0.27 H, 1-H minor), 7.3–7.4 (m, m, 1 H, OH), 4.91 (d, J4,5 = 9.3 Hz, 0.32 H, 4-H minor), 5.56 (s,
5 H, Ph), 7.58 (s, J1,NH = 13.4 Hz, 0.73 H, 1-H major), 9.78 (m,
0.32 H, PhCH minor), 5.67 (s, 0.68 H, PhCH major), 6.38 (m, 0.68
H, NH major), 7.31 (d, J1,NH = 13.0 Hz, 0.32 H, 1-H minor), 7.3–
0.27 H, NH minor) ppm. 13C NMR (125 MHz, [D6]DMSO, 25 °C)
δ = 12.8, 12.9 (CH3), 18.6, 32.1, 32.4 [(CH2)2], 46.1 (NCH2 major), 7.4 (m, 5 H, Ph), 7.73 (s, J1,NH = 13.0 Hz, 0.68 H, 1-H major),
47.2 (NCH2 minor), 49.2, 54.0 (CH2NCH2), 60.2 (C-5 minor), 61.2 10.02 (m, 0.32 H, NH minor) ppm. 13C NMR (125 MHz, [D6]-
(C-5 major), 66.7, 66.8 (CH2OCH2), 70.5 (C-6 major), 70.7 (C-6
minor), 78.5 (C-4 minor), 80.2 (C-4 major), 99.7 (PhCH major),
DMSO, 25 °C) δ = 29.2, 30.1, 30.3 (3 CH3), 50.0, 54.9 (CH2NCH2),
57.9 [NC(CH3)3], 61.2 (C-5 minor), 62.5 (C-5 major), 67.7, 67.9
100.0 (PhCH minor), 121.5 (C-2), 125.6–137.8 (Ph), 150.4 (C-1), (CH2OCH2), 71.4 (C-6 major), 71.6 (C-6 minor), 79.5 (C-4 minor),
186.7 (C-3 major), 191.4 (C-3 minor) ppm. MS (EI): m/z (%) = 390 81.9 (C-4 major), 100.6 (PhCH major), 100.9 (PhCH minor), 122.6
(100) [M]+. HRMS (EI): calcd. for C21H30N2O5 [M]+ 390.2155; (C-2 minor), 122.7 (C-2 major), 126.6–138.8 (Ph), 146.9 (C-1),
found 390.2145. C21H30N2O5 (390.47): calcd. C 64.59, H 7.74, N
7.17; found C 64.65, H 7.57, N 6.91.
187.9 (C-3 major), 192.2 (C-3 minor) ppm. MS (CI): m/z (%) = 391
(100) [M + H]+. HRMS (CI): calcd. for C21H31N2O5 [M + H]+
391.2233; found 391.2238. C21H30N2O5 (390.47): calcd. C 64.59, H
7.74, N 7.17; found C 64.65, H 7.17, N 6.91.
(4R,5R)-1-(Benzylamino)-4,6-O-(R)-benzylidene-2-morpholino-
4,5,6-trihydroxyhex-1-en-3-one (46): The syrupy compound was ob-
tained as a Z/E mixture in a 3:1 ratio; yield 0.30 g (71%). [α]D
–83.5 (c = 1.5, CH2Cl2). H NMR (500 MHz, [D6]DMSO, 25 °C): 2-morpholino-4,5,6-trihydroxyhex-1-en-3-one (49): The syrupy com-
=
(4R,5R)-4,6-O-(R)-Benzylidene-1-[(methoxycarbonylmethyl)amino]-
1
δ = 2.63, 2.83 (2 m, 4 H, CH2NCH2), 3.50 (t, J5,6a = J6a,6e
10.6 Hz, 1 H, 6a-H), 3.55 (m, 4 H, CH2OCH2), 3.84 (m, 0.75 H, 5-
=
pound was obtained as a Z/E mixture in a 3.5:1 ratio; yield 0.26 g
(64%). [α]D = –174.0 (c = 0.5, CH2Cl2). 1H NMR (500 MHz, [D6]-
Eur. J. Org. Chem. 2010, 4253–4265
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4263

F. Iglesias-Guerra, I. Periñán, M. Vega-Holm, J. M. Vega-Pérez
FULL PAPER
(Eds.: D. E. Levy, P. Fügedi), Taylor & Francis, Boca Raton,
FL, 2006, pp. 427–488.
J. M. Vega-Pérez, J. I. Candela, E. Blanco, F. Iglesias-Guerra,
Tetrahedron 1999, 55, 9641–9650.
J. M. Vega-Pérez, M. Vega, E. Blanco, F. Iglesias-Guerra, Tet-
rahedron: Asymmetry 2001, 12, 135–147.
DMSO, 25 °C): δ = 2.68, 2.89 (2 m, 4 H, CH2NCH2), 3.24 (m, 2
H, NCH2), 3.56 (t, J5,6a = J6a,6e = 10.5 Hz, 1 H, 6a-H), 3.64 (m, 4
H, CH2OCH2), 3.69, 3.70 (2 s, 3 H, NCH2CO2CH3), 3.91, 3.99 (2
m, 1 H, 5-H), 4.08 (m, 2 H, NCH2CO2CH3), 4.15 (m, 1 H, 6e-H),
4.36 (d, J4,5 = 9.1 Hz, 0.78 H, 4-H major), 4.68, 4.75 (2 m, 1 H,
OH), 4.89 (d, J4,5 = 9.4 Hz, 0.22 H, 4-H minor), 5.54 (s, 0.22 H,
PhCH minor), 5.58 (s, 0.78 H, PhCH major), 6.77 (m, 0.78 H, NH
major), 7.09 (d, J1,NH = 12.7 Hz, 0.22 H, 1-H minor), 7.3–7.4 (m,
5 H, Ph), 7.55 (s, J1,NH = 12.9 Hz, 0.78 H, 1-H major), 9.58 (m,
0.22 H, NH minor) ppm. 13C NMR (125 MHz, [D6]DMSO, 25 °C):
δ = 47.4 (NCH2 CO2 CH3 ), 49.1, 54.0 (CH2 NCH2 ), 51.2
(NCH2CO2CH3 major), 51.3 (NCH2CO2CH3 minor), 60.2 (C-5
minor), 61.0 (C-5 major), 66.7, 66.8 (CH2OCH2), 70.5 (C-6 major),
70.6 (C-6 minor), 78.5 (C-4 minor), 79.9 (C-4 major), 99.7 (PhCH
major), 100.0 (PhCH minor), 122.7 (C-2 minor), 122.9 (C-2 major),
125.6–137.7 (Ph), 150.1 (C-1 minor), 150.2 (C-1 major), 169.9
(NCH2CO2CH3 minor), 170.1 (NCH2CO2CH3 major), 187.4 (C-3
major), 192.4 (C-3 minor) ppm. MS (EI): m/z (%) = 406 (85) [M]
+. HRMS (EI): calcd. for C20H26N2O7 [M]+ 406.1740; found
406.1752.
[6]
[7]
[8]
a) J. M. Vega-Pérez, J. I. Candela, I. Romero, E. Blanco, F. Ig-
lesias-Guerra, Eur. J. Org. Chem. 2000, 3949–3956; b) J. M.
Vega-Pérez, M. Vega, E. Blanco, F. Iglesias-Guerra, Tetrahe-
dron: Asymmetry 2001, 12, 3189–3203; c) J. M. Vega-Pérez, J. I.
Candela, E. Blanco, F. Iglesias-Guerra, Tetrahedron: Asym-
metry 2002, 13, 2471–2783; d) J. M. Vega-Pérez, M. Vega, E.
Blanco, F. Iglesias-Guerra, Tetrahedron: Asymmetry 2004, 15,
3617–3633; e) J. M. Vega-Pérez, M. Vega, E. Blanco, F. Igles-
ias-Guerra, Tetrahedron: Asymmetry 2007, 18, 1850–1867.
a) J. M. Vega-Pérez, I. Periñán, M. Vega, F. Iglesias-Guerra,
Tetrahedron: Asymmetry 2008, 19, 1720–1729; b) J. M. Vega-
Pérez, I. Periñán, F. Iglesias-Guerra, Tetrahedron: Asymmetry
2009, 20, 1065–1072.
a) F. Iglesias-Guerra, I. Romero, F. Alcudia, J. M. Vega-Pérez,
Carbohydr. Res. 1998, 308, 57–62; b) F. Iglesias-Guerra, J. I.
Candela, J. Bautista, F. Alcudia, J. M. Vega-Pérez, Carbohydr.
Res. 1999, 316, 71–84; c) F. Iglesias-Guerra, J. I. Candela, E.
Blanco, F. Alcudia, J. M. Vega-Pérez, Chirality 2002, 14, 199–
203.
a) P. Nagaraj, N. G. Ramesh, Eur. J. Org. Chem. 2008, 4607–
4614; b) G. Zhang, Q. Liu, L. Shi, J. Wang, Tetrahedron 2008,
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a) H. Kim, H. Men, C. Lee, J. Am. Chem. Soc. 2004, 126,
1336–1337; b) V. D. Bussolo, J. Liu, L. G. Huffman Jr., D. Y.
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fith, S. J. Danishefsky, J. Am. Chem. Soc. 1991, 113, 5863–5864.
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[9]
[10]
(Z)-(4R,5R)-4,6-O-(R)-Benzylidene-1,2-dimorpholino-4,5,6-tri-
hydroxyhex-1-en-3-one (50): Yield 0.32 g (79%). [α]D = –79.2 (c =
1.0, CH2Cl2). 1H NMR (500 MHz, [D6]DMSO, 25 °C): δ = 2.95
(m, 4 H, CH2NCH2), 3.56–3.62 (m, 5 H, 6a-H, CH2OCH2), 3.65
(m, 4 H, CH2OCH2), 3.85 (m, 4 H, CH2NCH2), 3.91 (m, 1 H, 5-
H), 4.16 (dd, J5,6e = 5.4, J6a,6e = 10.7 Hz, 1 H, 6e-H), 4.41 (d, J4,5
= 9.0 Hz, 1 H, 4-H), 4.67 (m, 1 H, OH), 5.62 (s, 1 H, PhCH), 7.24
(s, 1 H, 1-H), 7.30–7.45 (m, 5 H, Ph) ppm. 13C NMR (125 MHz,
[D6]DMSO, 25 °C) δ = 49.2, 54.1 (2 CH2NCH2), 61.2 (C-5), 65.9,
66.0 (2 CH2OCH2), 70.4 (C-6), 80.2 (C-4), 99.7 (PhCH), 121.6 (C-
2), 125.6–137.8 (Ph), 147.6 (C-1), 189.9 (C-3) ppm. MS (CI): m/z
(%) = 405 (85) [M + H]+. HRMS (CI): calcd. for C21H29N2O6 [M
+ H]+ 405.2026; found 405.2013. C21H28N2O6 (404.46): calcd. C
62.36, H 6.98, N 6.93; found C 62.12, H 7.17, N 5.91.
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Acknowledgments
We thank the Junta de Andalucía (P06-FQM-01885), the Spanish
Ministerio de Educación y Ciencia (MEC) (CTQ2007-61185) and
the Federación Española de Enfermedades Raras (FEDER) for fi-
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Received: March 9, 2010
Published Online: June 21, 2010
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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