Indium-mediated reaction of 1-bromo-1-nitroalkanes with aldehydes: Access to 2-nitroalkan-1-ols

Article abstract of DOI:10.1002/ejoc.201000662

A novel method for the preparation of 2-nitroalkan-1-ols by an indium-promoted reaction of bromonitromethane with a variety of aldehydes is reported. The reaction was also performed with 2-bromo-2-nitropropanes to afford 2,2-dialkyl-2-nitroalkan-1-ols. The use of chiral sugar-derived aldehydes furnished the corresponding 2-nitroalkan-1-ols with excellent stereoselectivity. The utility of the novel sugar-derived 2,2-dialkyl-2-nitroalkan-1-ols for the preparation of branched iminosugar derivatives was demonstrated by the preparation of a hydroxymethyl branched polyhydroxylated azepane.

Full text of DOI:10.1002/ejoc.201000662

FULL PAPER
DOI: 10.1002/ejoc.201000662
Indium-Mediated Reaction of 1-Bromo-1-nitroalkanes with Aldehydes:
Access to 2-Nitroalkan-1-ols
Raquel G. Soengas*[a] and Amalia M. Estévez[b]
Keywords: Indium / Nucleophilic addition / Aldehydes / Aldol reactions / Iminosugars
A novel method for the preparation of 2-nitroalkan-1-ols by
an indium-promoted reaction of bromonitromethane with a
variety of aldehydes is reported. The reaction was also per-
formed with 2-bromo-2-nitropropanes to afford 2,2-dialkyl-2-
nitroalkan-1-ols. The use of chiral sugar-derived aldehydes
furnished the corresponding 2-nitroalkan-1-ols with excel-
lent stereoselectivity. The utility of the novel sugar-derived
2,2-dialkyl-2-nitroalkan-1-ols for the preparation of
branched iminosugar derivatives was demonstrated by the
preparation of a hydroxymethyl branched polyhydroxylated
azepane.
atoms to be linked together”.[5] Hence, sterically hindered
nitroalkanes are less reactive and usually fail to give the
desired nitro-aldol products in good yields. Thus, the nitro-
aldol condensation of α,α-dialkylnitroalkanes[6] has not
been widely used in organic synthesis, despite the usefulness
of the resulting 1,1-alkyl-1-nitroalkan-2-ols.[7]
To circumvent these limitations, it is of great interest to
develop alternative procedures for the preparation of 2-ni-
troalkan-1-ols that obviate the use of bases and allow β-
nitroalkanols derived from hindered nitroalkanes to be ob-
tained in good yields. A recent contribution by Concellon
et al.[8] consists of the SmI2-promoted reaction of bromoni-
tromethane with aldehydes,[9] an approach that allows 2-
nitroalkanols to be obtained in high yield and with good
stereoselectivity under very mild reaction conditions. On
other hand, the tin(II) chloride mediated addition of bro-
monitromethane to aldehydes was also recently de-
scribed.[10]
In connection with this work, we decided to investigate
an alternative approach based on an indium-promoted ad-
dition of α-bromo-α-nitroalkanes to aldehydes. Our aim
was to take advantage of the very low first ionization energy
of indium(0), which makes it an ideal candidate for use in
SET reactions. This property, together with its stability to
oxygen and water, prompted exhaustive studies focused on
the chemistry of indium with organic molecules in the past
several years.[11] The most common uses of indium in or-
ganic synthesis are in allylation reactions in Barbier-type
processes[12] and in metal-mediated Reformatsky reactions
between α-halocarbonyl compounds and aldehydes or
ketones.[13]
Introduction
The nitro-aldol reaction, often known as the Henry reac-
tion, has received a great deal of attention from the syn-
thetic community, as it is a powerful carbon–carbon bond-
forming reaction that proceeds under mild basic condi-
tions.[1] The reaction couples a carbonyl compound to a
nitroalkane bearing an α hydrogen atom, thereby creating a
β-nitroalkanol that can result in the formation of one or
two chiral centers. The classical Henry reaction, which in-
volves the base-catalyzed reaction of nitroalkanes and alde-
hydes, has been widely used in synthesis.[2] Moreover, the
true synthetic utility lies in further transformations of the
resulting β-nitroalkanols, including reduction, oxidation, or
dehydration.[3]
Nevertheless, the classical nitro-aldol reaction does suffer
from some important drawbacks. For example, the revers-
ibility of the reaction means that the β-nitroalkanols are
often obtained with poor stereochemical control.[3a] Al-
though several methods have been developed to avoid this
problem, they are often experimentally complex and in
most cases very specific conditions are required.[4] In ad-
dition, when either the starting carbonyl compound or the
resulting 2-nitro alcohols are base sensitive, the nitro-aldol
conditions can give rise to undesired side reactions that fur-
nish the target 2-nitroalkane-1-ols in low yields. On the
other hand, it is known that the nitro-aldol reaction is very
sensitive to steric factors and “becomes less and less satis-
factory the more substituents there are attached to the C
[a] Departamento de Química Fundamental, Universidade de A
Coruña,
Campus de A Zapateira, 15071 A Coruña, Spain
E-mail: rsoengas@udc.es
[b] Departamento de Química Orgánica, Universidade de Santiago
de Compostela,
Results and Discussion
15782 Santiago de Compostela, Spain
In our preliminary studies, the reaction of bromoni-
tromethane with aldehyde 1a was assessed at room tem-
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201000662.
View this journal online at
wileyonlinelibrary.com
5190
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 5190–5196

Indium-Mediated Reaction of 1-Bromo-1-nitroalkanes with Aldehydes
perature, under reflux, or under sonication, by using indium
These satisfactory results prompted us to extend these
(1–4 equiv.) and DMF, THF, and 75% aqueous methanol studies to conformationally restricted bromonitroalkane 6,
or 75% aqueous THF as the solvent (Scheme 1). The best which proved to be a suitable reagent for the preparation
results were achieved with solutions of aldehyde 1a of 1-substituted 2-(hydroxymethyl)-2-nitropropane-1,3-di-
(1 equiv.), indium (1 equiv.), and bromonitromethane ols recently used as highly valuable intermediates for access
(1.5 equiv.) in THF under sonication.
to branched-chain iminosugars of biological interest.[14]
Thus, reaction of 5-bromo-2,2-dimethyl-5-nitro-1,3-diox-
ane (6), easily prepared from the cheap, commercially avail-
able insecticide bronopol[15] (2-bromo-2-nitropropane-1,3-
diol), with aldehydes 1a–e (Scheme 3) gave the correspond-
ing substituted (2,2-dimethyl-5-nitro-1,3-dioxan-5-yl)meth-
anols 7a–e in moderate to good yields based on the reco-
vered starting material (Table 3).
Scheme 1. Indium-mediated reaction of aldehydes 1a–e and bromo-
nitromethane 2.
As shown by the results compiled in Table 1, under these
conditions linear aldehyde 1d, alicyclic aldehyde 1e, and
aromatic aldehydes 1a–c were efficiently converted into
their corresponding 2-nitroalkanols 3d, 3e, and 3a–c,
respectively. High yields were obtained, except for electron-
rich aryl aldehyde 1c, which as expected, proved to be sub-
stantially less reactive and yielded the corresponding adduct
3c (Table 1, Entry 3) in only 39% yield (together with 51%
of recovered starting material).
Scheme 3. Indium-mediated reaction of aldehydes 1a–e and 5-
bromo-2,2-dimethyl-5-nitro-1,3-dioxane (6).
Table 1. Synthesis of 2-nitroalkan-1-ols 3a–e.
Table 3. Synthesis of 1-substituted (2,2-dimethyl-5-nitro-1,3-di-
oxan-5-yl)methanols 7a–e.
Entry
1
R
3
Yield [%]
Entry
1
R
7
Yield[a] [%]
1
2
3
4
5
1a
1b
1c
1d
1e
C6H5
3a
3b
3c
3d
3e
80
91
39
78
81
55 (91)[b]
70 (94)
24 (83)
49 (82)
51 (88)
p-NO2C6H4
p-MeOC6H4
CH3(CH2)6
C6H11
1
2
2
2
5
1a
1b
1c
1d
1e
C6H5
7a
7b
7c
7d
7e
p-NO2C6H4
p-MeOC6H4
CH3(CH2)6
C6H11
In subsequent experiments aimed at extending these
studies to include hindered 1-bromo-1-nitroalkanes, the
case of 2-bromo-2-nitropropane (4) was considered first
(Scheme 2).
[a] Yield of isolated product (column chromatography) and yield
with respect to the recovered starting material (in brackets).
[b] Contaminated with 2,2-dimethyl-5-nitro-1,3-dioxane.
Regarding the mechanism of these indium-mediated
transformations, it should be noted that in contrast to the
SmI2-mediated reaction of bromonitromethane with alde-
hydes, which is promoted by the iodide released by the trace
amounts of SmI3, the synthesis of nitro alcohols 3a–e, 5a–
e, and 7a–e by using indium (1.0 equiv.) is consistent with
the typical role of indium as a monoelectronic reducing
agent in Barbier-type processes.[11] The satisfactory results
obtained in the synthesis of racemic nitro alcohols 3a–e,
5a–e, and 7a–e prompted us to test the usefulness of this
methodology for the synthesis of enantiopure 1-nitroalkan-
2-ols.
Scheme 2. Indium-mediated reaction of aldehydes 1a–e and 2-
bromo-2-nitropropane (4).
As shown in Table 2, the reaction of aldehydes 1a–e with
4 under the same reaction conditions as above gave mix-
tures of 2-nitroalkanols 5a–e and the corresponding start-
ing aldehydes 1a–e in all cases.
Our preliminary studies were carried out with a panel
consisting of chiral aldehydes 1f–i (Figure 1), which upon
reaction with bromonitromethane (2), under the same reac-
tion conditions as before, provided the corresponding 1-ni-
troalkan-2-ols 3f–i (Scheme 4) in high yields and good dia-
stereomeric ratios (Table 4). The major diastereomers were
always anti, as predicted by the Felkin–Anh model (Fig-
ure 2).
Better stereochemical results were obtained in the reac-
tions of aldehydes 1f–i with bromonitroalkanes 4 and 6
(Scheme 5). Good yields of a single diastereomer were ob-
tained in all cases, although, as in previous similar cases,
Table 2. Synthesis of 1-substituted 2-methyl-2-nitropropan-1-ols
5a–e.
Entry
1
R
5
Yield[a] [%]
1
2
3
4
5
1a
1b
1c
1d
1e
C6H5
5a
5b
5c
5d
5e
48 (89)
71 (94)
23 (90)
55 (88)
52 (91)
p-NO2C6H4
p-MeOC6H4
CH3(CH2)6
C6H11
[a] Yield of isolated product (column chromatography). The yield
with respect to the recovered starting material is given in parenthe-
ses.
Eur. J. Org. Chem. 2010, 5190–5196
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5191

R. G. Soengas, A. M. Estévez
FULL PAPER
Table 5. Synthesis of enantiopure 1-substituted 2-methyl-2-ni-
tropropan-1-ols 5f–i and 1-substituted (2,2-dimethyl-5-nitro-1,3-di-
oxan-5-yl)methanols 7f–i.
Entry Aldehyde Bromonitroalkane 2-Nitroalkan-1-ol Yield [%]
1
2
3
4
5
6
7
8
1f
1g
1h
1i
1f
1g
1h
1i
4
4
4
4
6
6
6
6
5f
5g
5h
5i
7f
7g
7h
7i
70
68
66
71
70
75
69
71
Figure 1. Chiral aldehydes 1f–i.
Scheme 4. Indium-mediated reaction of aldehydes 1f–i and bromo-
nitromethane (2).
Table 4. Synthesis of enantiopure 2-nitroalkan-1-ols 3f–i.
Entry Aldehyde 2-Nitroalkan-1-ol
Yield [%]
dr[a]
1
2
3
4
1f
1g
1h
1i
3f
3g
3h
3i
80
78
81
71
8:1, 5R/5S
9:1, 5R/5S
12:1, 2S/2R
12:1, 2S/2R
Figure 3. ORTEP diagram for 7f.
Henry reaction conditions would mainly lead to the Felkin–
Anh diastereomer, but due to the reversibility of the reac-
tion in basic media, this major component undergoes par-
tial epimerization at its stereogenic center bearing the hy-
droxy group, thereby affording a diastereomeric mixture.
Nitrosugar 8, a derivative of sugar-derived 1-substituted
2-(hydroxymethyl)-2-nitropropane-1,3-diol (7g), has re-
cently been reported as a highly valuable intermediate in
the synthesis of the branched-chain polyhydroxylated
1
[a] Calculated by H NMR spectroscopy.
Figure 2. Felkin–Anh model for the attack on sugar aldehydes 1f–i.
some starting material was always recovered (Table 5).
Mannose derivative 7f was unambiguously characterized by
X-ray diffraction (Figure 3).
Scheme 5. Indium-mediated reaction of aldehydes 1f–i and 2-
bromo-2-nitropropane (4) or 5-bromo-2,2-dimethyl-5-nitro-1,3-di-
oxane (6).
The excellent diastereoselectivity obtained in the ad-
dition of bromonitromethane (2) to aldehydes 1f–i and the
total stereocontrol achieved in the addition of the more hin-
dered nitrobromoalkanes 4 and 6 to aldehydes 1f–i, which
can easily be explained in terms of the Felkin–Anh model,
constitute clear advantages for the reported indium-medi-
ated access to 2-nitro-1-alkanols with respect to the classi-
Scheme 6. Reagents and conditions: (i) 1. Ammonium formate, pal-
ladium black, methanol, 50 °C, 20 h, 89%; 2. TFA/H2O, 1:1, room
temp., 16 h; 3. NaHCO3, THF, 40 °C, 24 h, 83%; (ii) 1. NaCNBH3,
AcOH, MeOH, room temp., 30 h; 2. AcCl, MeOH, room temp.,
cal Henry reaction. In fact, it is assumed that the classical 30 min, 78%.
5192
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 5190–5196

Indium-Mediated Reaction of 1-Bromo-1-nitroalkanes with Aldehydes
tively). Mass spectra were obtained with a Hewlett Packard 5988A
mass spectrometer. Thin-layer chromatography (TLC) was per-
formed by using Merck GF-254 type 60 silica gel and ethyl acetate/
hexane mixtures as eluents; the TLC spots were visualized with
Hanessian mixture. Column chromatography was carried out by
using Merck type 9385 silica gel. CCDC-785480 contains the sup-
plementary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
azepane 10, which was prepared in a global 15% yield from
-glucose by a route involving 11 steps.[14] This azepane has
now been obtained in a shorter and more efficient way, di-
rectly from derivative 7g, in the five-step sequence depicted
in Scheme 6. Thus, catalytic hydrogenation of 7g provided
the corresponding amine by reduction of the nitro group to
an amino and the removal of its benzyl group at the C-3
position. Once the isopropylidene groups were removed, the
resulting amino derivative was treated with base to afford
azepane 9, which was finally reduced to expected azepane
10. This compound was now obtained in 38% global yield
from -glucose in a six-step sequence.
General Procedure for the Reaction of Bromonitroalkanes and Alde-
hydes: To a suspension of indium powder (0.5 mmol) in THF
(1 mL) was added the bromonitroalkane (0.6 mmol), and the mix-
ture was sonicated for 20 min. The corresponding aldehyde
(0.5 mmol) was added, and sonication was continued for a further
4 h. The reaction mixture was neutralized with saturated aqueous
sodium hydrogen carbonate, diluted with water (10 mL), and ex-
tracted with diethyl ether (3ϫ25 mL). The combined organic layer
Conclusions
In conclusion, we report here novel access to 2-nitroalk- was dried with magnesium sulfate, filtered, and concentrated in
vacuo. The residue was purified by flash column chromatography
(ethyl acetate/hexane) to give the pure compounds shown in
Tables 1–3 and 5.
anols that consists of the indium-mediated addition of 1-
bromo-1-nitroalkanes to aldehydes. This strategy consti-
tutes a promising and convenient alternative to the classical
nitro-aldol (Henry) reaction. The approach is very simple
from an experimental point of view, and as bases are not
required, it is not subject to the limitations of the classical
Henry reaction. In addition, this approach may have many
advantages with respect to a previously reported samarium-
mediated Henry reaction of aldehydes with bromoni-
tromethane, which has not yet been described for more hin-
dered bromonitroalkanes and is more complex from an ex-
perimental point of view.
Regarding the stereoselective version of this novel ap-
proach to 2-nitroalkanols, promising results were achieved
when a panel of chiral sugar-derived aldehydes 1f–j was
treated with bromonitroalkanes 2, 4, and 6. The stereo-
chemistry results were strongly influenced by steric factors.
Thus, when the reaction was performed with bulky bromo-
nitroalkanes 4 and 6, the only diastereoisomeric 2-nitroalk-
anols obtained were those predicted by the Felkin–Anh
model.
2-Nitro-1-phenylethanol (3a): Aqueous workup gave 3a as a yellow
oil (66.8 mg, 80%). 1H NMR (CDCl3): δ = 2.87 (br. s, 1 H,OH),
4.53–4.61 (m, 2 H, 2-H), 5.29–5.50 (m, 1 H, 1-H), 7.41–7.43 (m, 5
H, Ar-H) ppm. 13C NMR (50 MHz, CDCl3): δ = 71.2, 81.3, 126.1,
129.0, 136.3 ppm.
2-Nitro-1-(4-nitrophenyl)ethanol (3b): Purification of the crude ma-
terial by flash column chromatography (ethyl acetate/hexane, 1:5)
1
afforded 3b (96.5 mg, 91%) as a white solid. H NMR (CDCl3): δ
= 3.19 (br. s, 1 H,OH), 4.55–4.65 (m, 2 H, 2-H), 5.63 (m, 1 H, 1-
H), 7.63 (d, J = 8.7 Hz, 2 H, 2 Ar-H), 8.28 (d, J = 8.7 Hz, 2 H, 2 H-
Ar) ppm. 13C NMR (CDCl3): δ = 75.3, 80.5, 124.1, 127.07, 143.2,
143.3 ppm.
1-(4-Methoxyphenyl)-2-nitroethanol (3c): Purification of the crude
material by flash column chromatography (ethyl acetate/hexane,
1:3) afforded 3c (38.4 mg, 39%) as a yellow oil. 1H NMR (CDCl3):
δ = 2.94 (br. s, 1 H, OH), 3.80 (s, 3 H, OCH3), 4.45 (dd, J2,1
3.5 Hz, J2,2Ј = 13.1 Hz, 1 H, 2-H), 4.59 (dd, J2,1 = 9.3 Hz, J2,2Ј
=
=
13.1 Hz, 1 H, 2Ј-H), 5.36–5.40 (m, 1 H, 1-H), 6.90 (d, J = 8.8 Hz,
2 H, 2 H-Ar), 7.30 (d, J = 8.8 Hz, 2 H, 2 H-Ar) ppm. 13C NMR
(CDCl3): δ = 55.5, 70.8, 81.4, 114.6, 127.5, 130.4, 160.2 ppm.
As a first practical application of the indium chemistry
reported here, and in connection with our present interest
in novel synthetic applications of nitrosugars, a new route
to branched-chain polyhydroxylated azepane 9 was devel-
oped. This approach is shorter and more efficient than the
previously reported synthetic route.
1-Nitrononan-2-ol (3d): After aqueous workup, 3d was obtained as
a yellow oil (73.7 mg, 78%). 1H NMR (CDCl3): δ = 0.84 (t, J =
6.6 Hz, 3 H, CH3), 1.19–1.54 (m, 12 H), 4.22–4.29 (m, 1 H), 4.32–
4.39 (m, 2 H) ppm. 13C NMR (CDCl3): δ = 14.0, 22.5, 25.0, 28.9,
29.9, 33.4, 72.0, 80.9 ppm.
Work is now in progress aimed at developing a systematic
study of the mechanistic and stereochemical aspects of this
novel and highly promising route to 2-nitroalkan-1-ols. The
use of this method as a key step in the synthesis of a family
of branched-chain iminosugars is also under investigation.
1-Cyclohexyl-2-nitroethanol (3e): After aqueous workup, 3e was ob-
tained as a yellow oil (70.0 mg, 81%). 1H NMR (CDCl3): δ = 0.90–
1.73 (m, 11 H), 4.03–4.11, 4.33–4.45 (2 m, 3 H, 1-H, 2-H, 2Ј-H)
ppm. 13C NMR (CDCl3): δ = 25.7, 25.9, 26.1, 27.9, 28.8, 41.4, 72.8,
79.3 ppm.
2-Methyl-2-nitro-1-phenylpropan-1-ol (5a): Purification of the crude
material by flash column chromatography (ethyl acetate/hexane,
1:7) afforded 5a (41.5 mg, 48%) as a yellow oil, together with some
starting aldehyde (21.7 mg, 41%). 1H NMR (CDCl3): δ = 1.41 and
1.55 (2 s, 6 H, 2 CH3), 2.64 (d, J = 1.4 Hz, 1 H, OH), 5.27 (d, J =
1.4 Hz, 1 H, 1-H), 7.32–7.36 (m, 5 H, 5 H-Ar) ppm. 13C NMR
(CDCl3): δ = 18.8, 24.9, 71.2, 81.3, 126.1, 129.0, 129.5, 136.3 ppm.
Experimental Section
General: Reactions under sonication were carried out with a Selecta
cleaning bath (320 W) at 20 °C. Melting points were determined
by using a Kofler Thermogerate apparatus. Specific rotations were
recorded with a JASCO DIP-370 optical polarimeter. Nuclear mag-
netic resonance spectra were recorded with a Varian Mercury plus
2-Methyl-2-nitro-1-(4-nitrophenyl)propan-1-ol (5b): Purification of
the crude material by flash column chromatography (ethyl acetate/
200 spectrometer (200 and 50 MHz for H and 13C nuclei, respec-
1
Eur. J. Org. Chem. 2010, 5190–5196
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5193

R. G. Soengas, A. M. Estévez
hexane, 1:6) afforded 5b (85.2 g, 71%) as a white solid, together (ethyl acetate/hexane, 1:3) afforded 7d (70.8 mg, 49%) as a yellow
FULL PAPER
1
with some starting aldehyde (15.6 mg, 23%). H NMR (acetone):
δ = 1.48 and 1.55 (2 s, 6 H, 2 CH3), 5.49 (d, J = 4.6 Hz, 1 H), 5.59
(d, J = 4.6 Hz, 1 H), 7.64 (d, J = 8.8 Hz, 2 H, 2 H-Ar), 8.25 (d, J
= 8.8 Hz, 2 H, 2 H-Ar) ppm. 13C NMR (acetone): δ = 19.7, 24.1,
77.6, 92.6, 123.8, 129.9, 148.2 ppm.
oil, together with some starting aldehyde (21.1 mg, 33%). 1H NMR
(CDCl3): δ = 0.84 (t, J = 4.8 Hz, 3 H, CH3), 1.23–1.43 (m, 18 H),
2.28 (d, J = 7.8 Hz, 1 H, OH), 3.78–3.87 (m, 1 H, 2-H), 4.08 (d, J
= 13.1 Hz, 1 H, CHO), 4.18 (d, J = 13.1 Hz, 1 H, CHO), 4.42–
4.49 (m, 2 H, 2 CHO) ppm. 13C NMR (CDCl3): δ = 14.2, 21.0,
22.7, 25.9, 26.1, 29.3, 31.5, 31.9, 61.6, 62.2, 73.0, 90.5, 99.5 ppm.
MS (ESI): m/z (%) = 290.20 (81) [M + H]+, 248.09 (62) [M + Na]+.
HRMS: calcd. for C14H28NO5 [M + H]+ 290.1967; found 290.1967.
1-(4-Methoxyphenyl)-2-methyl-2-nitropropan-1-ol (5c): Purification
of the crude material by flash column chromatography (ethyl acet-
ate/hexane, 1:6) afforded 5c (28.9 mg, 23%) as a yellow oil, together
1
Cyclohexyl(2,2-dimethyl-5-nitro-1,3-dioxan-5-yl)methanol (7e): Pu-
rification of the crude material by flash column chromatography
(ethyl acetate/hexane, 1:5) afforded 7e (69.6 mg, 51%) as a yellow
oil, together with some starting aldehyde (20.7 mg, 37%). 1H NMR
(CDCl3): δ = 1.09–1.22, 1.43–1.70 (m, 11 H), 1.34 and 1.43 (2 s, 6
H, 2 CH3), 2.32 (br. s, 1 H, OH), 3.67 (d, J = 8.6 Hz, 1 H, 1-H),
4.01–4.24 (m, 2 H, CH2O), 4.44–4.54 (m, 2 H, CH2O) ppm. 13C
NMR (CDCl3): δ = 21.0, 25.9, 26.0, 26.2, 26.3, 26.5, 32.4, 39.6,
62.4, 62.7, 77.3, 90.3, 99.5 ppm. MS (ESI): m/z (%) = 274.16 (54)
[M + H]+, 296.15 (26) [M + Na]+. HRMS: calcd. for C13H24NO5
[M + H]+ 274.1648; found 274.1653.
with some starting aldehyde (50.6 mg, 67%). H NMR (CDCl3): δ
= 1.41 and 1.55 (2 s, 6 H, 2 CH3), 3.79 (s, 3 H, OCH3), 5.23 (br. s,
1 H, OH), 5.28 (s, 1 H, 1-H), 6.88 (d, 2 H, 2 H-Ar), 7.28 (d, 2 H,
2 H-Ar) ppm. 13C NMR (CDCl3): δ = 19.2, 24.4, 55.4, 77.9, 92.4,
113.7, 128.8, 130.6, 159.9 ppm.
2-Methyl-2-nitrodecan-3-ol (5d): Purification of the crude material
by flash column chromatography (ethyl acetate/hexane, 1:3) af-
forded 5d (59.7 mg, 55%) as a yellow oil, together with some start-
1
ing aldehyde (21.1 mg, 33%). H NMR (CDCl3): δ = 0.86 (t, J =
5.6 Hz, 3 H, CH3), 1.26–1.54 (m, 18 H), 3.95–4.00 (m, 1 H, 2-H)
ppm. 13C NMR (CDCl3): δ = 14.3, 20.5, 24.0, 22.8, 26.6, 29.4, 29.6,
31.7, 32.0, 76.2, 92.4 ppm.
1-O-tert-Butyldimethylsilyl-6-deoxy-2,3-di-O-isopropylidene-6-nitro-
α-D-mannofuranose (3f): Purification of the crude material by flash
1-Cyclohexyl-2-methyl-2-nitropropan-1-ol (5e): Purification of the
crude material by flash column chromatography (ethyl acetate/hex-
ane, 1:7) afforded 5e (52.2 mg, 52%) as a yellow oil, together with
some starting aldehyde (21.8 mg, 39%). 1H NMR (CDCl3): δ =
1.15–1.71 (m, 17 H), 3.40–3.51 (m, 1 H, 1-H) ppm. 13C NMR
(CDCl3): δ = 22.4, 23.8, 26.1, 26.6, 27.0, 28.9, 32.3, 39.8, 79.8,
92.0 ppm.
column chromatography (ethyl acetate/hexane, 1:7) afforded 3f
(145 mg, 80%) as a clear oil. [α]2D4 = +33.9 (c = 1.4, CHCl3). 1H
NMR (CDCl3): δ = 0.04 and 0.07 (2 s, 6 H, SiMe2), 0.84 [s, 9 H,
SiC(CH3)3], 1.31 and 1.46 (2 s, 6 H, 2 CH3), 3.01 (br. s, 1 H, OH),
3.91–3.95 (m, 1 H), 4.44–4.55 (m, 4 H), 4.82–4.87 (m, 1 H), 5.29
(s, 1 H, 1-H) ppm. 13C NMR (CDCl3): δ = –5.5, –4.5, 18.0, 24.5,
25.5, 25.8, 67.2, 78.4, 79.2, 79.4, 86.5, 101.4, 113.0 ppm. MS (ESI):
m/z (%) = 381.21 (100) [M + Na]+, 364.18 (20) [M + H]+. HRMS:
calcd. for C15H30NO7Si [M + H]+ 364.1786; found 364.1787.
(2,2-Dimethyl-5-nitro-1,3-dioxan-5-yl)(phenyl)methanol (7a): Purifi-
cation of the crude material by flash column chromatography (ethyl
acetate/hexane, 1:3) afforded an inseparable 2:1 mixture of 7a and
2,2-dimethyl-5-nitro-1,3-dioxane (73.4 mg, 55%) as a white solid,
together with some starting aldehyde (19.1 mg, 36%). 1H NMR
(CDCl3): δ = 1.31 (s, 6 H, 2 CH3), 4.12–4.43 (m, 4 H, 2 CH2O),
5.09 (s, 1 H, 1-H), 7.22–7.25 (m, 2 H, 2 H-Ar), 7.34–7.37 (m, 3 H,
3 H-Ar) ppm. 13C NMR (CDCl3): δ = 20.8, 26.2, 61.3, 61.8, 75.1,
89.5, 99.3, 126.8, 129.0, 129.6, 137.0 ppm.
3-O-Benzyl-6-deoxy-6-nitro-1,2-O-isopropylidene-α-D-glucofuranose
(3g): Purification of the crude material by flash column chromatog-
raphy (ethyl acetate/hexane, 1:3) afforded 3g (132 mg, 78%) as a
yellow oil. [α]2D0 = –36.2 (c = 1.1, CHCl3). H NMR (CDCl3): δ =
1
1.31 and 1.47 (2 s, 6 H, 2 CH3), 4.06 (d, J = 3.1 Hz, 1 H), 4.21–
4.25 (m, 1 H), 3.41–4.82 (m, 6 H), 5.89 (d, J1,2 = 3.7 Hz, 1 H, 1-
H), 7.15–7.38 (m, 10 H, 10 H-Ar) ppm. 13C NMR (CDCl3): δ =
26.7, 27.21, 72.22, 73.8, 74.2, 77.9, 79.9, 81.7, 81.9, 105.4, 112.6,
128.0, 128.2, 128.3, 128.4, 128.7, 128.9, 137.3, 137.7 ppm.
(2,2-Dimethyl-5-nitro-1,3-dioxan-5-yl)(4-nitrophenyl)methanol (7b):
Purification of the crude material by flash column chromatography
(ethyl acetate/hexane, 1:2) afforded 7b (109 mg, 70%) as a white
solid, together with some starting aldehyde (23.1 mg, 34%). 1H
NMR (acetone): δ = 1.26 and 1.39 (2 s, 6 H, 2 CH3), 4.35–4.41 (m,
4 H, 2 CH2O), 5.39 (d, J = 3.5 Hz, 1 H, 1-H), 5.81 (d, J = 3.5 Hz,
1 H, OH), 7.64 (d, 2 H, 2 H-Ar), 8.22 (d, 2 H, 2 H-Ar) ppm. 13C
NMR (acetone): δ = 20.3, 27.3, 62.4, 62.5, 73.5, 90.1, 99.4, 124.1,
129.2, 131.4, 146.7 ppm. MS (ESI): m/z (%) = 313.10 (8) [M +
H]+. HRMS: calcd. for C13H17N2O7 [M + H]+ 313.1030; found
313.1045.
5-O-tert-Butyldimethylsilyl-1-deoxy-1-nitro-3,4-O-isopropylidene-D-
ribitol (3h): Purification of the crude material by flash column
chromatography (ethyl acetate/hexane, 1:7) afforded 3h (185.9 mg,
81%) as a white solid. M.p. 98–100 °C (Et2O/hexane). [α]2D2 = –14.8
1
(c = 3.7, CHCl3). H NMR (CDCl3): δ = 1.04 [s, 9 H, C(CH3)3],
1.27 and 1.30 (2 s, 6 H, 2 CH3), 3.66–3.70 (dd, J4,5 = 3.6 Hz, J5,5Ј
= 11.0 Hz, 1 H, 5-H), 3.90 (dd, J4,5Ј = 9.2 Hz, J5,5Ј = 11.0 Hz, 1 H,
5Ј-H), 4.08–4.16 (m, 1 H), 4.28–4.39 (m, 2 H), 4.52 (dd, J1,2
=
9.6 Hz, J1,1Ј = 13.0 Hz, 1 H, 5Ј-H), 4.70–4.76 (m, 1 H), 7.36–7.44
(m, 5 H, 5 H-Ar), 7.60–7.69 (m, 4 H, 4 H-Ar) ppm. 13C NMR
(CDCl3): δ = 19.2, 25.3, 26.9, 27.9, 62.5, 67.6, 76.8, 77.52, 78.7,
109.4, 128.2, 130.5, 131.8, 135.6, 135.7 ppm. MS (ESI): m/z (%) =
482.20 (100) [M + Na]+, 460.21 (14) [M + H]+. HRMS: calcd. for
C24H34NO6Si [M + H]+ 460.2149; found 460.2159.
(4-Methoxyphenyl)(2,2-dimethyl-5-nitro-1,3-dioxan-5-yl)methanol
(7c): Purification of the crude material by flash column chromatog-
raphy (ethyl acetate/hexane, 1:2) afforded 7c (33.5 mg, 24%) as a
yellow oil, together with some starting aldehyde (44.5 mg, 59%).
1H NMR (CDCl3): δ = 1.31 and 1.32 (2 s, 6 H, 2 CH3), 2.58 (br.
s, 1 H, OH), 3.79 (s, 3 H, OCH3), 4.13–4.19 (m, 2 H, CH2O), 4.37–
4.41 (m, 2 H, CH2O), 5.04 (d, J = 3.1 Hz, 1 H, 1-H), 6.87 (ABq, 2
H, 2 H-Ar), 7.15 (ABq, 2 H, 2 H-Ar) ppm. 13C NMR (CDCl3): δ
= 20.8, 26.3, 55.5, 61.3, 61.8, 74.9, 89.6, 99.3, 114.3, 128.0, 128.9,
160.5 ppm. MS (ESI): m/z (%) = 320.11 (6) [M + Na]+. HRMS:
calcd. for C14H19NO6Na [M + Na]+ 320.1104; found 320.1098.
5-O-tert-Butyldimethylsilyl-1-deoxy-1-nitro-3,4-O-isopropylidene-L-
lyxitol (3i): Purification of the crude material by flash column
chromatography (ethyl acetate/hexane, 1:5) afforded 3i (162.9 mg,
71 %) as a yellow oil. 1H NMR (CDCl3): δ = 1.04 [s, 9 H,
C(CH3)3], 1.33 and 1.36 (2 s, 6 H, 2 CH3), 3.56–3.58 (m, 1 H),
3.65–4.03 (m, 3 H), 4.29–4.68 (m, 3 H), 7.39–7.42 (m, 5 H, 5 H-
Ar), 7.62–7.66 (m, 4 H, 4 H-Ar) ppm. 13C NMR (CDCl3): δ = 19.3,
27.0, 64.7, 70.6, 78.6, 79.5, 80.5, 110.2, 128.1, 128.2, 130.3, 130.4,
1-(2,2-Dimethyl-5-nitro-1,3-dioxan-5-yl)-1-nitronoan-2-ol (7d): Puri-
fication of the crude material by flash column chromatography
5194
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 5190–5196

Indium-Mediated Reaction of 1-Bromo-1-nitroalkanes with Aldehydes
132.4, 132.5, 135.8 ppm. MS (ESI): m/z (%) = 482.20 (75) [M +
HRMS: calcd. for C20H38NO9Si [M + H]+ 464.2310; found
Na]+, 460.21 (15) [M + H]+. HRMS: calcd. for C24H34NO6Si [M 464.2325.
+ H]+ 460.2149; found 460.2158.
3-O-Benzyl-(5R)-(2,2-dimethyl-5-nitro-1,3-dioxan-5-yl)-1,2-O-iso-
propylidene-α- -xylofuranose (7g): Purification of the crude mate-
1-O-tert-Butyldimethylsilyl-2,3-di-O-isopropylidene-(5R)-(1-methyl-
1-nitroethyl)-α- -lyxofuranose (5f): Purification of the crude mate-
D
D
rial by flash column chromatography (ethyl acetate/hexane, 1:3) af-
forded 7g (164.6 mg, 75%) as a yellow oil. [α]2D4 = –39.7 (c = 1.2,
CHCl3). 1H NMR (CDCl3): δ = 1.34/1.39/1.43/1.45 (4 s, 12 H, 4
CH3), 4.05–4.34 (m, 5 H), 4.42–4.57 (m, 5 H), 5.91 (d, J1,2 = 3.7 Hz,
1 H, 1-H), 7.24–7.36 (m, 5 H, 5 H-Ar) ppm. 13C NMR (CDCl3):
δ = 20.6, 21.5, 25.6, 26.5, 61.1, 62.8, 70.4, 72.4, 78.7, 81.3, 82.5,
90.2, 99.5, 105.6, 112.6, 128.3, 128.9, 129.2, 136.8 ppm. MS (ESI):
m/z (%) = 440.19 (21) [M + H]+, 462.17 (100) [M + Na]+. HRMS:
calcd. for C21H30NO9 [M + H]+ 440.1915; found 440.1894.
rial by flash column chromatography (ethyl acetate/hexane, 1:7) af-
forded 5f (136.8 mg, 70%) as a yellow oil. [α]2D3 = –21.3 (c = 0.4,
1
CHCl3). H NMR (CDCl3): δ = 0.04 and 0.08 (2 s, 6 H, SiMe2),
0.83 [s, 9 H, SiC(CH3)3], 1.31 and 1.47 (2 s, 6 H, 2 CH3), 1.61 (s,
6 H, 2 CH3), 2.85 (d, J = 5.6 Hz, 1 H, OH), 3.80–4.48 (m, 2 H),
4.53–4.63 (m, 1 H), 4.84 (dd, J = 3.8 Hz, J = 5.8 Hz, 1 H), 5.09 (s,
1 H, 1-H) ppm. 13C NMR (CDCl3): δ = –5.5, –4.5, 18.2, 21.0, 24.0,
25.0, 26.3, 69.6, 73.9, 79.3, 81.1, 84.3, 91.1, 106.13, 113.12 ppm.
MS (ESI): m/z (%) = 392.21 (12) [M + H]+. HRMS: calcd. for
C17H34NO7Si [M + H]+ 392.2105; found 392.2117.
4-O-tert-Butyldiphenylsilyl-2,3-di-O-isopropylidene-(1S)-(2,2-dimeth-
yl-5-nitro-1,3-dioxan-5-yl)-D-erythrol (7h): Purification of the crude
material by flash column chromatography (ethyl acetate/hexane,
1:5) afforded 7h (192.8 mg, 69%) as a yellow oil. [α]2D2 = –26.9 (c =
1.7, CHCl3). 1H NMR (CDCl3): δ = 1.03 [s, 9 H, SiC(CH3)3], 1.26/
3-O-Benzyl-1,2-O-isopropylidene-(5R)-(1-methyl-1-nitroethyl)-α-D-
xylofuranose (5g): Purification of the crude material by flash col-
umn chromatography (ethyl acetate/hexane, 1:4) afforded 5g
1
(124 mg, 68%) as a yellow oil. [α]2D3 = –11.3 (c = 0.2, CHCl3). H
1.28/1.37/1.43 (4 s, 12 H, 4 CH3), 3.57 (dd, J4,5 = 2.0 Hz, J5,5Ј
=
NMR (CDCl3): δ = 1.32/1.47/1.60/1.64 (4 s, 12 H, 4 CH3), 4.03–
4.13 (m, 2 H), 4.39–4.43 (m, 1 H), 4.45 (d, J = 7.9 Hz, 1 H, CHPh),
4.58 (d, J1,2 = 2.5 Hz, 1 H, 2-H), 4.75 (d, J = 7.9 Hz, 1 H, CHPh),
5.93 (d, J1,2 = 2.5 Hz, 1 H, 1-H), 7.33–7.39 (m, 5 H, 5 H-Ar) ppm.
13C NMR (CDCl3): δ = 19.7, 24.8, 26.4, 26.9, 72.2, 72.3, 79.5, 81.3,
82.3, 91.8, 105.7, 112.0, 128.2, 128.6, 129.0, 137.2 ppm. MS (ESI):
m/z (%) = 390. 15 (100) [M + Na]+ . HRMS: calcd. for
C18H25NO7Na [M + Na]+ 390.1523; found 390.1525.
7.2 Hz, 1 H, 5-H), 3.76 (t, J4,5Ј = 7.2 Hz, J5,5Ј = 7.2 Hz, 1 H, 5Ј-
H), 4.24–4.37 (m, 4 H), 4.47–4.68 (m, 3 H), 7.39–7.48 (m, 5 H, Ar-
H), 7.58–7.65 (m, 4 H, Ar-H) ppm. 13C NMR (CDCl3): δ = 19.1,
20.3, 25.3, 26.8, 27.9, 26.8, 61.2, 62.1, 62.5, 69.7, 76.4, 77.3, 89.9,
99.2, 109.6, 128.2, 130.5, 131.6, 131.7, 135.5, 135.6 ppm. MS (ESI):
m/z (%) = 560.27 (18) [M + H]+, 582.25 (100) [M + Na]+. HRMS:
calcd. for C29H41NO8NaSi [M + Na]+ 582.2493; found 582.2478.
4-O-tert-Butyldiphenylsilyl-2,3-di-O-isopropylidene-(1S)-(2,2-dimeth-
yl-5-nitro-1,3-dioxan-5-yl)-D-threitol (7i): Purification of the crude
4-O-tert-Butyldiphenylsilyl-2,3-di-O-isopropylidene-(1S)-(1-methyl-
1-nitroethyl)-D-erythrol (5h): Purification of the crude material by
material by flash column chromatography (ethyl acetate/hexane,
2:9) afforded 7i (170.5 mg, 61%) as a yellow oil. 1H NMR (CDCl3):
δ = 1.05 [s, 9 H, SiC(CH3)3], 1.33/1.36/1.39/1.46 (4 s, 12 H, 4 CH3),
3.50–3.54 (m, 1 H), 3.54–4.05 (m, 1 H), 4.15–4.31 (m, 2 H), 4.57–
4.71 (m, 2 H), 7.40–7.44 (m, 5 H, Ar-H), 7.62–7.65 (m, 4 H, Ar-
H) ppm. 13C NMR (CDCl3): δ = 19.2, 20.1, 26.7, 26.9, 27.1, 61.9,
62.2, 65.0, 73.6, 79.1, 80.4, 89.8, 99.2, 110.5, 128.2, 130.4, 131.9,
135.7 ppm. MS (ESI): m/z (%) = 560.27 (22) [M + H]+, 582.25
(100) [M + Na]+. HRMS: calcd. for C29H41NO8NaSi [M + Na]+
582.2493; found 582.2481.
flash column chromatography (ethyl acetate/hexane, 1:4) afforded
5h (160.7 mg, 66%) as a yellow oil. [α]2D3 = –22.9 (c = 1.1, CHCl3).
1H NMR (CDCl3): δ = 1.04 [s, 9 H, C(CH3)3], 1.27 and 1.30 (2 s,
6 H, 2 CH3), 1.41 (s, 6 H, 2 CH3), 3.72–3.86 (m, 3 H), 3.49–4.50
(m, 2 H), 7.39–7.45 (m, 5 H, 5 H-Ar), 7.64–7.73 (m, 4 H, 4 H-Ar)
ppm. 13C NMR (CDCl3): δ = 19.3, 25.0, 25.4, 27.0, 61.3, 72.4, 79.7,
81.0, 91.1, 110.9, 127.9, 120.0, 128.2, 128.3, 130.0, 135.7, 135.8,
135.9 ppm. MS (ESI): m/z (%) = 505.27 (100) [M + Na]+, 488.25
(25) [M + H]+. HRMS: calcd. for C26H38NO6Si [M + H]+
488.2462; found 488.2471.
(2R,3R,4S,5R,6R)-7,7-Bis(hydroxymethyl)azepane-2,3,4,5,6-pentaol
(9): Palladium black (0.06 g, 20% w/w) and ammonium formate
(1.05 g, 16.56 mmol) were added to a degassed solution of 7g
(0.27 g, 0.61 mmol) in methanol (6 mL), and the resulting mixture
was stirred under a nitrogen atmosphere at 50 °C for 24 h. The
suspension was then filtered through Celite, and the solvent was
evaporated in vacuo to give 5(R)-(2,2-dimethyl-5-amino-1,3-di-
oxan-5-yl)-1,2-O-isopropylidene-α--xylofuranose (0.17 g, 89%
yield) as a clear oil. [α]2D4 = –33.6 (c = 1.0, CHCl3). 1H NMR
(CDCl3): δ = 1.29/1.41/1.50 (3 s, 12 H, 4 CH3), 3.56–3.62 (m, 2 H,
CH2O), 3.79 (d, J4,5 = 7.2 Hz, 1 H, 5-H), 3.96–4.04 (m, 3 H, CH2O,
4-H), 4.31 (d, J3,4 = 1.4 Hz, 1 H, 3-H), 4.50 (d, J1,2 = 4.0 Hz, 1 H,
2-H), 5.91 (d, J1,2 = 4.0 Hz, 1 H, 1-H) ppm. 13C NMR (CDCl3): δ
= 19.1, 26.1, 26.8, 27.9, 52.0, 65.6, 67.7, 70.7, 75.7, 79.5, 84.9, 98.7,
105.0, 111.7 ppm. MS (ESI): m/z (%) = 320.17 (100) [M + H]+.
HRMS: calcd. for C14H26NO7 [M + H]+ 320.1703; found 320.1698.
4-O-tert-Butyldiphenylsilyl-2,3-di-O-isopropylidene-(1S)-(1-methyl-
1-nitroethyl)-D-threitol (5i): Purification of the crude material by
flash column chromatography (ethyl acetate/hexane, 1:4) afforded
1
5i (172.9 mg, 71%) as a yellow oil. H NMR (CDCl3): δ = 1.08 [s,
9 H, C(CH3)3], 1.27 and 1.29 (2 s, 6 H, 2 CH3), 1.67 and 1.69 (2 s,
6 H, 2 CH3), 3.66–3.74 (m, 1 H), 3.83–3.90 (m, 2 H), 4.10–4.23 (m,
2 H), 7.35–7.48 (m, 5 H, 5 H-Ar), 7.66–7.73 (m, 4 H, 4 H-Ar) ppm.
13C NMR (CDCl3): δ = 19.3, 21.6, 23.3, 26.6, 26.7, 65.2, 76.3, 79.6,
81.0, 91.3, 110.2, 127.6, 127.7, 127.8, 128.0, 128.1, 135.6,
135.7 ppm. MS (ESI): m/z (%) = 505.27 (100) [M + Na]+, 488.25
(20) [M + H]+. HRMS: calcd. for C26H38NO6Si [M + H]+
488.2462; found 488.2484.
1-O-tert-Butyldimethylsilyl-2,3-di-O-isopropylidene-(5R)-(2,2-dimeth-
yl-5-nitro-1,3-dioxan-5-yl)-α-D-lyxofuranose (7f): Purification of the
crude material by flash column chromatography (ethyl acetate/hex-
ane, 1:3) afforded 7f (162.0 mg, 70%) as a white solid. M.p. 123– A solution of 5(R)-(2,2-dimethyl-5-amino-1,3-dioxan-5-yl)-1,2-O-
125 °C (Et2O/hexane). [α]2D5 = +22.6 (c = 1.0, CHCl3). 1H NMR
isopropylidene-α--xylofuranose (0.17 g, 0.61 mmol) in a mixture
(CDCl3): δ = 0.10/0.11 (2 s, 6 H, SiMe2), 0.86 [s, 9 H, SiC(CH3)3], of triuoroacetic acid and water (2:1, 9 mL) was stirred at room
1.29/1.35/1.42/1.46 (4 s, 12 H, 4 CH3), 3.01 (br. s, 1 H, OH), 4.07– temperature for 4 h. The solvents were removed in vacuo, and the
4.29 (m, 4 H), 4.46–4.83 (m, 4 H), 5.30 (s, 1 H, 1-H) ppm. 13C was residue coevaporated with toluene (3ϫ5 mL) to afford a crude
NMR (CDCl3): δ = –5.5, –4.5, 17.8, 19.8, 24.6, 25.5, 25.9, 27.0,
yellow oil that was dissolved in THF (9 mL). Sodium hydrogen
carbonate (0.077 g, 0.915 mmol) was added (0.15 g, 0.61 mmol),
61.5, 62.2, 70.5, 78.3, 80.6, 85.8, 89.2, 98.9, 101.7, 112.7 ppm. MS
(ESI): m/z (%) = 464.23 (31) [M + H]+, 486.21 (9) [M + Na]+. and the resulting mixture was heated at 40 °C for 24 h, after which
Eur. J. Org. Chem. 2010, 5190–5196
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5195

R. G. Soengas, A. M. Estévez
FULL PAPER
[5] D. Seebach, F. Lehr, Angew. Chem. Int. Ed. Engl. 1976, 15, 505.
[6] a) G. Rosini, R. Ballini, P. Sorrenti, M. Petrini, Synthesis 1984,
7, 607; b) J.-M. Melot, F. Texier-Boullet, A. Foucaud, Tetrahe-
dron Lett. 1986, 27, 493; c) Y. J. Chen, W. Y. Lin, Tetrahedron
1993, 49, 10263; d) T. Kolter, G. van Echten-Deckert, K. Sand-
hoff, Tetrahedron 1994, 50, 13425; e) R. Ballini, G. Bosica, P.
Forconi, Tetrahedron 1996, 52, 1677; f) V. J. Bulbule, V. H.
Deshpande, S. Velu, A. Sudalai, S. Sivasankar, V. T. Sathe, Tet-
rahedron 1999, 55, 9325; g) K. Akutu, H. Kabashima, T. Seki,
H. Hattori, Appl. Cat. A General 2003, 247, 65; h) R. Ballini,
D. Fiorini, M. V. Gil, A. Palmieri, Tetrahedron 2004, 60, 2799.
[7] a) D. Crich, K. Ranganathan, S. Rumthao, M. Shirai, J. Org.
Chem. 2003, 68, 2034; b) F. A. Luzzio, J. P. Ott, D. Y. Duveau,
J. Org. Chem. 2006, 71, 5027; c) D. Crich, M. Shirai, F. Bre-
bion, S. Rumthao, Tetrahedron 2006, 62, 6501.
TLC (chloroform/methanol/water/acetic acid, 60:30:5:3) showed
that the starting material had been consumed. The solvent was
evaporated in vacuo, and the resulting residue was dissolved in ace-
tone. The solution was filtered, and the filtrate was concentrated
under reduced pressure. The residue was puried by flash column
chromatography (chloroform/methanol/water, 40:10:1) to give 9
(0.12 g, 0.51 mmol, 83% yield) as a yellow oil. [α]2D3 = –13.9 (c =
1
1.3, CH3OH). H NMR (D2O): δ = 3.39 (s, 1 H, NH), 3.46 (d, 1
H, J5,6 = 8.4 Hz, 6-H), 3.57 (dd, 1 H, J2,3 = 1.2 Hz, J3,4 = 7.3 Hz,
3-H), 3.71 (dd, 1 H, J = 2.3 Hz, J = 10.4 Hz, CHOH), 3.77–3.80
(m, 3 H, 5-H, CH2OH), 3.87–3.91 (m, 2 H, 4-H, CHOH), 4.99 (d,
1 H, J2,3 = 1.2 Hz, 2-H) ppm. 13C NMR (D2O): δ = 61.4, 67.0,
69.0, 69.3, 71.6, 72.2, 77.3, 94.4 ppm. MS (ESI): m/z (%) = 240
(100) [M + H]+, 222 (34) [M + H2O]+. HRMS: calcd. for
C8H18NO7 [M + H]+ 240.1083; found 240.1077.
[8] J. M. Concellón, H. Rodríguez-Solla, C. Concellón, J. Org.
Chem. 2006, 71, 7919.
[9] Reaction of bromonitromethane and aldehydes to give 2-
bromo-2-nitroalkan-1-ols was also described: a) J. M. Concel-
lon, H. Rodriguez-Solla, C. Concellon, S. Garcia-Granda,
M. R. Diaz, Org. Lett. 2006, 8, 5979; b) G. Blay, V. Hernández-
Olmos, J. R. Pedro, Chem. Commun. 2008, 4840.
[10] A. S. Mahasneh, Z. Naturforschung B: Chem. Sci. 2005, 60,
416.
[11] Reviews on indium chemistry: a) P. Cintas, Synlett 1995, 1089;
b) C. J. Li, Tetrahedron 1996, 52, 5643; c) J. A. Marshall, Chem-
tracts, Org. Chem. 1997, 10, 481; d) C. J. Li in Green Chemistry,
Frontiers in Benign Chemical Syntheses and Processes (Eds.: P.
Anastas, T. C. Williamson), Oxford University Press, New
York, 1998, ch. 14; e) L. A. Paquette, Green Chemistry, Fron-
tiers in Benign Chemical Syntheses and Processes (Eds.: P. An-
astas, T. C. Williamson), Oxford University Press, New York,
1998, ch. 15; f) C. J. Li, T. K. Chan, Tetrahedron 1999, 55,
11149.
(3R,4R,5R,6S)-2,2-Bis(hydroxymethyl)azepane-3,4,5,6-tetraol Hy-
drochloride (10): Sodium cyanoborohydride (0.045 g, 0.71 mmol)
was added to a solution of 9 (0.034 g, 0.14 mmol) in methanol/
acetic acid (98:2, 1 mL). The mixture was stirred at room tempera-
ture for 24 h. The solvents were removed in vacuo, after which the
residue was dissolved in anhydrous methanol (1 mL) and acetyl
chloride (0.1 mL) was added dropwise. The mixture was stirred for
30 min, and the resulting white solid was filtered off and washed
with diethyl ether (5 mL) to afford 10 (0.028 g, 0.11 mmol, 78%
yield). [α]2D3 = –5.6 (c = 1.1, CH3OH). H NMR (D2O): δ = 3.41–
1
3.58 (m, 3 H, 7-H, 7Ј-H, 6-H), 3.89–4.18 (m, 7 H, 3-H, 4-H, 5-H,
2 CH2OH) ppm. 13C NMR (D2O): δ = 44.1, 59.5, 59.9, 66.4, 70.0,
71.8, 72.4, 74.6 ppm. MS (ESI): m/z (%) = 224 (60) [M – Cl]+, 206
(100) [M – Cl + H2O]+. HRMS: calcd. for C8H18NO6 [M – Cl]+
224.1134; found 224.1133.
[12] a) S. Araki, N. Katsamura, K. Kawasaki, Y. Butsugan, J.
Chem. Soc. Perkin Trans. 1 1991, 53, 499; b) T. H. Chan, C. J.
Li, Tetrahedron Lett. 1991, 32, 7017; c) T. H. Chan, M. B.
Isaak, Tetrahedron Lett. 1995, 36, 8957; d) T. H. Chan, M. C.
Lee, J. Org. Chem. 1995, 60, 4228; e) L. A. Paquette, T. H. Mit-
zel, J. Am. Chem. Soc. 1996, 118, 1931; f) B. Alcaide, P. Al-
mendros, R. Rodríguez-Acebes, J. Org. Chem. 2002, 67, 1925;
g) E. Levoirier, Y. Canac, S. Norsikian, A. Lubineau, Car-
bohydr. Res. 2004, 339, 2737; h) E. Balla, A. Zamyatina, A.
Hofinger, P. Kosma, Carbohydr. Res. 2007, 342, 2537.
[13] a) R. D. Rieke, L. C. Chao, J. Org. Chem. 1975, 40, 2253; b) S.
Araki, Y. Butsugan, J. Org. Chem. 1988, 53, 1831; c) J. Podlech,
T. C. Maier, Synthesis 2003, 633; d) V. Nair, R. Ros, C. N.
Jayan, B. Pillai, Tetrahedron 2004, 60, 1959; e) S. A. Babu, M.
Yasuda, I. Shibata, A. Baba, J. Org. Chem. 2005, 70, 10408.
[14] a) J. Otero, R. G. Soengas, J. C. Estévez, R. J. Estévez, G. W. J.
Fleet, D. J. Watkin, Org. Lett. 2007, 9, 623; b) J. Otero, A. M.
Estévez, R. G. Soengas, R. J. Nash, J. C. Estévez, G. W. J. Fleet,
R. J. Estévez, Tetrahedron: Asymmetry 2008, 19, 2443.
Supporting Information (see footnote on the first page of this arti-
cle): Copies of the 13C NMR spectra for compounds 3, 5, and 7.
Acknowledgments
This work was supported by the Spanish Ministry of Science and
Innovation (CTQ2008-06493). R.G.S. thanks the Xunta de Galicia
for financial support (Isidro Parga Pondal program) and A.M.E. is
indebted to the Spanish Ministry of Science and Innovation for an
FPU grant. We would like to thank Professors Ramón J. Estévez,
Juan. C. Estévez, and L. Sarandeses for helpful discussions.
[1] L. Henry, Bull. Soc. Chim. Fr. 1895, 13, 999.
[2] a) F. A. Luzzio, Tetrahedron 2001, 57, 915; b) C. Palomo, M.
Oiarbide, A. Mielgo, Angew. Chem. Int. Ed. 2004, 43, 5442.
[3] a) N. Ono, The Nitro Group in Organic Synthesis, Wiley-VCH,
Weinheim, 2001; b) H. Feuer (Ed.), Organic Nitro Chemistry [15] G. Calvet, R. Guillot, N. Blanchard, A. Kovklovsky, Org. Bi-
Series; Wiley-VCH, Weinheim, 2001, ch. 2.
[4] C. Palomo, M. Oiarbide, A. Laso, Eur. J. Org. Chem. 2007,
2561 and references cited therein.
omol. Chem. 2005, 3, 4395
Received: May 9, 2010
Published Online: July 30, 2010
5196
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 5190–5196