The use of samarium or sodium iodide salts as an alternative for the aza-Henry reaction

Article abstract of DOI:10.1016/j.tet.2011.12.061

A novel reaction of bromonitromethane with a variety of imines in very mild conditions promoted by SmI₂ and NaI to afford nitroamines or bromonitroamines is described. When these reactions were performed on sugar-based imines, the corresponding

Full text of DOI:10.1016/j.tet.2011.12.061

Tetrahedron 68 (2012) 1736e1744
Contents lists available at SciVerse ScienceDirect
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journal homepage: www.elsevier.com/locate/tet
The use of samarium or sodium iodide salts as an alternative for the aza-Henry
reaction
,
a
a
b
Humberto Rodríguez-Solla a , Carmen Concellon , Noemí Alvaredo , Raquel G. Soengas
*
ꢀ
a
ꢀ
ꢀ
ꢀ
Departamento de Química Organica e Inorganica, Facultad de Química, Universidad de Oviedo, Julian Clavería 8, 33071 Oviedo, Spain
Centro Singular de Investigacion en Química Biologica y Materiales Moleculares, Campus Vida, Universidad de Santiago de Compostela, Calle Jenaro de la Fuente s/n,
b
ꢀ
ꢀ
15782 Santiago de Compostela, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel reaction of bromonitromethane with a variety of imines in very mild conditions promoted by
SmI2 and NaI to afford nitroamines or bromonitroamines is described. When these reactions were
performed on sugar-based imines, the corresponding nitroamines or bromonitroamines were obtained
in high yields and from moderate to good stereoselectivities. Synthetic possibilities of nitroamines were
also shown by their reduction with SmI2/H2O in the presence of pyrrolidine at room temperature. A
mechanism is proposed for this novel aza-Henry reaction.
Received 17 November 2011
Received in revised form 7 December 2011
Accepted 20 December 2011
Available online 24 December 2011
Keywords:
Aza-Henry
Carbohydrates
Diamines
Ó 2011 Elsevier Ltd. All rights reserved.
Nitronates
Samarium
1. Introduction
first asymmetric aza-Henry reaction, in which binaphtoxide
(BINOL)-based heterobimetallic complexes of ytterbium and alu-
The aza-Henry reaction, also called nitro-Mannich reaction, in-
volves the nucleophilic addition of nitroalkanes to imines and is of
prime importance for the synthesis of nitrogen-containing mole-
cules. This reaction results in the formation of a carbonecarbon
minum were used as catalysts.8
Since Anderson and Shibasaki pioneering works, the aza-Henry
reaction has attracted considerable chemical attention. So far, both
racemic and asymmetric methods for the reactions with various
nitroalkanes were realised using inorganocatalysts,9 organo-
catalysts,10 or chiral Lewis acid catalysts of ytterbium,8 aluminum,11
copper,12 and zinc13 metals.
Previously, we have described two addition reactions of bromo-
nitromethane to aldehydes to give nitroalkan-2-ols14 or 1-bromo-1-
nitroalkan-2-ols.15 These transformations took place under very
mild reaction conditions and were promoted by samarium diiodide
or sodium iodide, respectively. Both Henry reactions could be ap-
plied to the preparation of enantiopure compounds, starting from
chiral N,N-dibenzyl aminoaldehydes. Thus, enantiopure (2R,3S)-3-
bond with concomitant generation of a b-nitroamine. From a syn-
thetic point of view, this method presents important synthetic
applications as a wide variety of other organic compounds can be
accessed by functional transformations of the nitro group into other
1
chemical functionalities, such as amines, carbonyl groups,2 hy-
droxylamines,3 and oximes or nitriles,4 providing access to valuable
functionalized structural motifs such as 1,2-diamines.5
As the aza-Henry reaction has long been known,6 it is un-
derstandable that significant efforts have been devoted over the
years to improve the yields and stereocontrol of the process. Sur-
prisingly, no significant success has been achieved until the last few
years. Unlike the addition of nitronates to aldehydes, the addition
to imines is thermodynamically not favored. On the one hand,
Anderson et al. reasoned that, as nitronates are quite inert toward
Schiff bases, the aid of a Lewis or Brønsted acid is required,
reporting an improved version of the classical nitro-Mannich re-
action.7 On the other hand, Shibasaki et al. described in 1999 the
amino-1-nitroalkan-2-ols
or
(1S,2S,3S)-3-amino-1-bromo-1-
nitroalkan-2-ols were obtained with good stereoselectivity.
Herein we report our results concerning the addition of bro-
monitronate to a wide range of aldimines being the process pro-
moted by catalytic amounts of sodium iodide to afford 1-bromo-1-
nitroalkan-2-amines in nearly quantitative yields. Alternatively, the
synthesis of 1-nitroalkan-2-amines can be achieved by using sub-
stoichiometric amounts of samarium diiodide or triiodide. Prepa-
ration of nitroamines or bromonitroamines derived from sugars is
also reported. This transformation took place from moderate to
good stereoselectivities and in absence of epimerization.
* Corresponding author. E-mail address: hrsolla@uniovi.es (H. Rodríguez-Solla).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.12.061

H. Rodríguez-Solla et al. / Tetrahedron 68 (2012) 1736e1744
1737
Imines 1 derived from p-toluenesulfonamide, and used as
SmI2
starting materials, were prepared in high yields according to
a method previously reported in the literature.16 Initially, we
studied the addition reaction of bromonitromethane 2 to imines 1
promoted by samarium diiodide. Thus, the treatment of a solution
I
SmIX
Pg
N
SmIX
1/2 IX
O
N
Pg
R
R1
N
O
N
OSmIX
1
Br
N
O
of bromonitromethane
2 (1 equiv) and the N-tosylimine 1a
O
O
(1 equiv) in THF with a solution of 0.35, 0.5, and 1.0 equiv of SmI2 in
THF (0.1 M)17 at room temperature gave in all cases the corre-
sponding compound 3a. The best results, in terms of yield (96%
yield) and cleanliness of the crude material, were obtained using
1.0 equiv of SmI2. When 0.35 or 0.5 equiv of SmI2 were utilized, 69
and 87% yield of 3a were obtained, respectively. For this reason
entries shown in Table 1 were carried out using 1 equiv of SmI2 for
5 h at room temperature.
5
1/2 IX
2
4
X = Br, I
H3O+
NHPg
NO2
SmIII
O
N
R
3
O
3
A
Table 1
Scheme 1. Proposed mechanism for the synthesis of compounds 3.
Synthesis of 2-amino-1-nitroalkanes 3
Pg
NHPg
NO2
SmI2
THF
H2O in the presence of pyrrolidine at room temperature).19 To our
surprise, when these conditions were employed, 1,2-
diaminoalkanes were obtained in high yields (Table 2) and no
nitroamines were isolated.20
N
Br
NO2
R1
R1
H
1
2
3
Entry
1
3
R1
Pg
Yielda (%)
SmI2
Table 2
Synthesis of 1,2-diaminoalkanes 6
SmI3
1
2
3
4
5
6
7
8
1a
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
n-C7H15
s-Bu
c-C6H11
PhCH2CH2
Ph
p-CNC6H4
n-C7H15
i-Pr
Ts
Ts
Ts
Ts
Ts
Ts
PMP
PMP
PMP
PMP
PMP
PMP
PMP
BOC
BOC
BOC
96
95
88
89
56
58
92
90
87
87
84
64
61
65
60
67
89
83
77
78
NHTs
NHTs
SmI2 / H2O
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
NO2
NH2
R1
R1
, THF
3
6
N
H
Yielda (%)
9
s-Bu
Entry
3
6
R1
n-C7H15
c-C6H11
PhCH2CH2
10
11
12
13
14
15
16
c-C6H11
1
2
3
3a
3c
3d
6a
6b
6c
89
83
77
b
C10H19
Ph
p-CNC6H4
Ph
p-CNC6H4
p-MeOC6H4
a
Isolated yield of analytically pure compounds 6.
a
Taking into account both, the synthetic possibilities of an acti-
vated C-halogen bond and our previous report on the synthesis of
1-bromo-1-nitroalkan-2-ols,15 we also tested the utilization of so-
dium iodide as a catalytic reagent for the synthesis of 1-bromo-1-
nitroalkan-2-amines. Accordingly, when a solution of a variety of
aldimines 1 (1.0 equiv) in THF and 1.0 equiv of bromonitromethane
2 were treated with 0.15 equiv of sodium iodide at room temper-
ature for 3 h, 2-amino-1-bromo-1-nitroalkanes 7 were obtained in
high yields (Table 3).
Isolated yield of analytically pure compounds 3.
(E)-EtCH]CH(CH2)5.
b
It is also worth of mention the use of substoichiometric amounts
of SmI2 to generate a nitronate intermediate. To explain these re-
sults, a mechanism based on the typical SmI2 role as mono-
electronic reducing agent in a Barbier-type process through the
metalation of the CeBr bond should be discarded, as 2 equiv of SmI2
would be required. We then assume that the synthesis of com-
pounds 3 could be initiated by the iodide released from the SmI3
traces, which are present in the THF solutions of SmI2 (Scheme
1).14,18 Thus the iodide would attack to the bromine atom of bro-
monitromethane generating a samarium (III) nitronate anion 4 and
Table 3
Synthesis of 2-amino-1-bromo-1-nitroalkanes 7
Pg
NHPg
N
NaI cat.
IBr. The addition of 4 to the imine would generate the samarium b-
NO2
Br
NO2
R1
R1
H
nitroamide 5 that would afford compounds 3 after hydrolysis. The
employment of lower amount of SmI2 (0.35 or 0.5 equiv) could be
explained taking into account that the samarium alcoholate 4
might also act as a source of halogen (iodide or bromide). So, after
two additional halogen-release, species such as the samarium tris-
nitronate A could be generated affording compounds 5, which, after
hydrolysis yielded nitroaldol compounds 3. A proof of this pro-
posed mechanism is based on the synthesis of products 3aed in
high yields using SmI3 instead of SmI2 (Table 1, entries 1e4).
The obtained 2-amino-1-nitroalkanes 3 can be versatile starting
materials due to their high functionality. Attempts to deprotect the
tosyl group were carried out on substrates 3a, 3c, and 3d under the
conditions previously reported by Hilmersson and Anker (SmI2/
THF
Br
7
1
2
Entry
1
7
R1
Pg
Yielda (%)
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1j
1n
1o
1p
7a
7b
7c
7d
7e
7f
n-C7H15
s-Bu
c-C6H11
PhCH2CH2
c-C6H11
Ph
p-CNC6H4
p-MeOC6H4
Ts
Ts
Ts
Ts
PMP
BOC
BOC
BOC
98
98
94
99
94
63
60
65
7g
7h
a
Isolated yield after filtration or column chromatography based on compounds 1.

1738
H. Rodríguez-Solla et al. / Tetrahedron 68 (2012) 1736e1744
In general terms, crude reaction products were obtained in high
case of aromatic aldimines 1lep where slightly higher yields were
obtained. (6) Other iodide sources different than SmI2 and NaI, such
as SmI3 and LiI or KI could be used to perform both aza-Henry re-
actions. As it can be envisaged in Table 1, slightly lower yields of
purity, after filtration through a pad of Celite and further solvent
removal under vacuum. No column chromatography purification
was necessary to obtain compounds 7aee excepting 7feh (derived
from aromatic imines). Compounds 7 were isolated with high pu-
rity and as a mixture of diastereoisomers in approximately 1:1
ratio, determined by 1H analysis of the crude reaction products
(Table 3).
This transformation took place based, on one hand, due to the
high acidity of bromonitromethane 2 and, on the other hand, taking
into account that although the iodide is a very weak base in an
aqueous medium, in THF could be sufficiently strong to abstract an
acidic proton from bromonitromethane. Thus, an acidebase re-
action of bromonitromethane with the iodide anion could generate
a bromonitronate intermediate 9 that could react with aldimines 1
to afford the amides 8, which after protonolysis with the in situ
generated hydrogen iodide would generate the corresponding
bromonitroamine 7 releasing the iodide anion that would continue
the catalytic system (Scheme 2).
compounds
3 were obtained (entries 1e4) when SmI3 was
employed instead of SmI2. On the other hand longer reaction time
was required (18 h) in the reactions promoted by LiI or KI affording
the corresponding compound 7a (from 1a) in similar yields to those
obtained using NaI (Table 3).
The satisfactory results obtained in the synthesis of racemic
nitro amines 3 and bromonitroamines 7 prompted us to test the
usefulness of this methodology for the synthesis of chiral sugar-
derived enantiopure diamines.
Chiral enantiopure diamines are useful synthetic intermediates
and are of great interest for the development of new chiral ligands
for asymmetric synthesis. Particularly appropriate for these pur-
poses are 1,2-diamines containing a sugar residue.22
Our studies were carried out with N-p-methoxyphenylimines
10, which upon reaction with bromonitromethane (1.0 equiv) and
SmI2 in THF (1.0 equiv, 0.1 M) provided the corresponding nitro
amines 11 in high yields and diastereoisomeric ratio ranging be-
tween 5/1 and 2/1 (Table 4).
NHPg
I-
NO2
R
Br
Br
NO2
Br
7
Table 4
2
Synthesis of carbohydrate-derived aminonitroalkanes 11
O-
N
PgN-
R
PMP
SmI2
THF
NHPMP
R1
N
NO2
O-
Br
NO2
O2N
R1
HI
9
Br
8
10
2
11
Entry
10
11
R1
dra
Yieldb (%)
O
O
Pg
1
2
3
10a
11a
11b
11c
5/1
90
86
81
N
O
BnO
R
1
O
O
Scheme 2. Proposed mechanism for the synthesis of compounds 7.
10b
10c
4/1
O
MeO
O
O
The different behavior of the iodide atoms depending on their
cationic partner (Smþ2 or Smþ3 in comparison with Naþ) could be
rationalized considering the ionic (Naþ) or covalent (Smþ3) char-
acter of these species. So, iodide from NaI could be completely
dissociated and could abstract acidic hydrogens, whereas iodide
from Smþ3 species would be partially bonded to the samarium
center decreasing the basic properties of these iodide ions.
OTBS
2.5/1
O
O
O
O
4
10d
11d
2/1
76
O
O
In general terms, as it can be envisaged in Tables 1 and 3, it is
noteworthy that: (1) the addition reaction of bromonitronate in-
termediate to aldimines was not reported to date and constitutes
an interesting synthetic method due to the low cost of the catalyst
used. (2) The unreported use of substoichiometric amounts of sa-
marium di- or triiodide to promote the aza-Henry reactions from
a wide range of aldimines is an attractive synthetic methodology to
choose due to its high efficiency and the quantitative yields ob-
tained. (3) The addition reaction of the samarium nitronate or so-
dium bromonitronate to imines seems to be general as it was
proved by performing the reaction from aliphatic (linear, cyclic, or
branched) or aromatic (electron rich or deficient) aldimines 1 as
starting materials. (4) 2-Amino-1-nitroalkanes 3 and 2-amino-1-
bromo-1-nitroalkanes 7 were obtained in very high yields. (5) In
both syntheses, the reaction has also been carried out on N-(p-
methoxyphenyl)imines 1gem21 (Table 1, entries 7e13; Table 3,
entry 5), and N-Boc imines 1neo (Table 1, entries 14e16; Table 3,
entries 6e8) and no important differences were observed when
compared with the reaction of N-tosylimines 1aef excepting the
a
dr was determined by 300 MHz 1H NMR analysis of the crude products 11.
Isolated yield of pure compounds 11 after column chromatography based on
b
compounds 10.
In subsequent experiments aimed at extending these studies to
include the preparation of sugar-derived 1-bromo-1-nitroalkan-2-
amines, we also tested the utilization of sodium iodide as a cata-
lytic reagent. Thus, reaction of the N-p-methoxyphenylimines 10a
and 10c, with bromonitromethane (1 equiv) and NaI (0.15 equiv) in
THF provided the corresponding bromonitroamines 12 in high
yields and moderate diastereoisomeric ratio. When the reaction
was performed at lower temperatures (0 ꢀC), no differences were
observed on the stereoselectivity of this process (Table 5).
The absolute configuration of the major stereoisomer 1-bromo-
1-nitroalkan-2-amine 12a was established by X-ray diffraction
(Fig. 1).23 The structure and the absolute configuration of 1-bromo-
1-nitroalkan-2-amine 12b were assigned by analogy.

H. Rodríguez-Solla et al. / Tetrahedron 68 (2012) 1736e1744
1739
Table 5
In conclusion, we have described a novel reaction of bromo-
nitromethane with a variety of imines in very mild conditions
promoted by SmI2 and NaI to afford nitroamines or bromonitro-
amines, respectively. Regarding the stereoselective version of this
novel approach to 2-nitro amines, promising results were ach-
ieved when chiral sugar-derived imines 10 were reacted with
bromonitromethane in the presence of both, SmI2 and NaI. The
chiral 2-nitroamines 11 and 12 obtained were those predicted
by the FelkineAhn model. Other synthetic applications of
these reactions and studies directed toward fully delineating the
factors involved in these transformations are currently under
investigation.
Synthesis of carbohydrate-derived bromonitroamines 12
PMP
NHPMP
R1
N
NaIcat.
THF
O2N
Br
NO2
R1
10
Br
2
12
Entry
1
10
12
R1
dra
Yieldb (%)
O
O
10a
12a
2.5/1
1.5/1
83
72
O
BnO
O
O
2. Experimental section
OTBS
3
10c
12b
2.1. General procedures for the synthesis of imines (1)
O
2.1.1. Synthesis of N-tosylimines (1aef). A mixture of the corre-
sponding aldehyde (10.0 mmol, 1.0 equiv), p-toluenesulfonamide
(10.0 mmol, 1.0 equiv), sodium p-toluenesulfinate (10.0 mmol,
1.0 equiv) in formic acid (95%, 15 mL), and H2O (15 mL) was stirred
for 24 h at room temperature. The resulting white precipitate was
collected by filtration, washed with H2O (3ꢁ10 mL), and hexane
(2ꢁ10 mL), then dissolved in CH2Cl2 (100 mL), followed by addition
of H2O (35 mL) and aqueous saturated solution of NaHCO3 (35 mL).
The solution was then stirred for 10 min at room temperature. The
organic phase was collected, and the aqueous phase was extracted
with CH2Cl2 (3ꢁ70 mL). The combined organic layers were dried
over NaSO4, concentrated to yield the corresponding N-sulfonyl
imine as a colorless oil or white solid. Aliphatic imines were used
without further purification, and aromatic imines were purified by
trituration with water and hexane.
a
dr was determined by 300 MHz 1H NMR analysis of the crude products 12.
Isolated yield of pure compounds 12 after column chromatography based on
b
compounds 10.
2.1.2. Synthesis of N-(p-methoxyphenyl)imines (1gem). The ali-
phatic p-methoxyphenylimines 1gej were prepared in nearly
quantitative yields by stirring for 2 h a solution in CH2Cl2 of the
corresponding aldehyde (10 mmol, 1.0 equiv) with p-anisidine
(10 mmol, 1.0 equiv) in the presence of MgSO4 (2 g). For the syn-
thesis of aromatic imines 1kem, the reaction time was increased to
16 h. Compounds 1kem were purified by recrystallization in
ethanol.
Fig. 1. Ortep diagram for 12a.
It is noteworthy that no significant differences were observed on
the reaction of N-p-methoxyphenylimines derived from carbohy-
drates 10 when compared with the reaction of N-p-methox-
yphenylimines 1gem.
2.1.3. Synthesis of N-tert-butoxycarbonylimines (1nep). Compounds
1nep were prepared following the method previously described in
the literature.
The stereoselectivity obtained in the addition of bromonitro-
methane 2 to imines 10 can easily be explained through the Fel-
kineAhn model; the nitronate (X¼H) or bromonitronate (X¼Br)
attack on the si face giving preferentially to the anti-stereoisomers
(Scheme 3).24 This mechanistic proposal was confirmed by X-ray
diffraction of compound 12a (Fig. 1).
2.1.4. Synthesis of 2-amino-1-nitroalkanes (3). SmI2 or SmI3
(0.8 mmol, 1 equiv) in THF (8 mL) was added to a stirred solution of
bromonitromethane 2 (0.8 mmol, 1 equiv) and the corresponding
imines 1 (0.8 mmol, 1 equiv) in THF (5 mL). After stirring the re-
action mixture at room temperature for 5 h it was quenched with
aqueous HCl (10 mL, 0.1 M) and then, the organic material was
extracted with dichloromethane. The combined extracts were
washed with an aqueous saturated solution of Na2S2O3, then dried
over Na2SO4, and the solvents were removed under reduced pres-
sure affording compounds 3, which were purified by column
chromatography (hexane/EtOAc 3:1).
OMe
N
2.1.4.1. 1-Nitro-N-tosylnonan-2-amine (3a). Yellow solid; mp
O
O
134e137 ꢀC; 1H NMR (300 MHz, CDCl3):
d
7.79 (d, J¼8.4 Hz, 2H),
N
7.33 (d, J¼8.4 Hz, 2H), 5.48 (d, J¼8.5 Hz,1H), 4.51 (dd, J¼12.7, 5.2 Hz,
1H), 4.39 (dd, J¼12.7, 5.8 Hz, 1H), 3.83e3.72 (m, 1H), 2.44 (s, 3H),
1.53e1.40 (m, 2H), 1.29e0.98 (m, 10H), 0.86 (t, J¼7.0 Hz, 3H); 13C
O
H
H
X
10
4 X = H
9 X = Br
NMR (75 MHz, CDCl3):
d
143.9 (C), 136.9 (C), 129.7 (2ꢁ CH), 127.0
(2ꢁ CH), 78.5 (CH2), 51.6 (CH), 32.2 (CH2), 31.4 (CH2), 28.8 (CH2),
Scheme 3. Mechanism for the addition of nitronates to sugar-derived imines 10.
28.6 (CH2), 25.1 (CH2), 22.4 (CH2), 21.4 (CH3), 13.9 (CH3); MS (ESIþ)

1740
H. Rodríguez-Solla et al. / Tetrahedron 68 (2012) 1736e1744
m/z (%) 343 ([MþH]þ, 47), 283 (6), 282 (100), 128 (10); HRMS (ESIþ)
calcd for [C16H27N2O4S]þ [MþH]þ 343.1692, found 343.1686; IR
(neat): 3304, 1558, 1380, 1344, 1161 cmꢂ1; Rf¼0.50 (hexane/EtOAc
3:1).
2.1.4.7. 4-Methoxy-N-(1-nitrononan-2-yl)benzenamine
(3g). Brown oil; 1H NMR (300 MHz, CDCl3):
6.64 (d, J¼8.5 Hz, 2H), 4.51 (dd, J¼11.5, 4.9 Hz, 1H), 4.41 (dd, J¼11.5,
5.7 Hz, 1H), 3.98e3.87 (m, 1H), 3.75 (s, 3H), 1.71e1.27 (m, 12H), 0.88
d
6.80 (d, J¼8.5 Hz, 2H),
(t, J¼6.2 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 152.9 (C), 139.9 (C),
2.1.4.2. 3-Methyl-1-nitro-N-tosylpentan-2-amine (3b). Orange
115.3 (2ꢁ CH), 115.0 (2ꢁ CH), 78.0 (CH2), 55.6 (CH3), 53.5 (CH), 32.8
(CH2), 31.6 (CH2), 29.2 (CH2), 28.9 (CH2), 25.8 (CH2), 22.5 (CH2), 13.9
(CH3); MS (ESIþ) m/z (%) 295 ([MþH]þ, 100), 234 (5), 214 (4), 201
(7); HRMS (ESIþ) calcd for [C16H27N2O3]þ [MþH]þ 295.2022, found
295.2016; IR (neat): 3380, 1550, 1513, 1381, 1243 cmꢂ1; Rf¼0.48
(hexane/EtOAc 5:1).
solid; mp 137e140 ꢀC; 1H NMR (300 MHz, CDCl3):
d 7.75e7.66 (m,
4H), 7.25e7.20 (m, 4H), 5.45 (d, J¼9.0 Hz, 1H), 5.36 (d, J¼8.7 Hz, 1H),
4.44e4.23 (m, 4H), 3.81e3.64 (m, 2H), 2.36 (s, 3H), 2.35 (s, 3H),
1.55e0.78 (m, 6H), 0.78e0.71 (m, 6H), 0.64 (t, J¼7.3 Hz, 6H); 13C
NMR (75 MHz, CDCl3):
d 143.9 (C), 143.4 (C), 139.0 (C), 136.7 (C),
129.7 (2ꢁ CH), 129.6 (2ꢁ CH), 127.0 (2ꢁ CH), 126.2 (2ꢁ CH), 76.7
(CH2), 76.2 (CH2), 56.0 (CH), 55.0 (CH), 37.0 (CH), 36.3 (CH), 25.4
(CH2), 24.7 (CH2), 21.5 (CH3), 21.4 (CH3), 14.7 (CH3), 13.7 (CH3), 11.1
(2ꢁ CH3); MS (ESIþ) m/z (%) 318 ([MþNa]þ, 100), 301 ([MþH]þ, 47),
241 (4), 240 (66); HRMS (ESIþ) calcd for [C13H21N2O4S]þ [MþH]þ
301.1222, found 301.1216; IR (neat): 3379, 1558, 1380, 1266,
1164 cmꢂ1; Rf¼0.36 (hexane/EtOAc 3:1).
2.1.4.8. 4-Methoxy-N-(3-methyl-1-nitrobutan-2-yl)benzenamine
(3h). Brown oil; 1H NMR (300 MHz, CDCl3):
d
6.79 (d, J¼7.2 Hz, 2H),
6.64 (d, J¼7.2 Hz, 2H), 4.48 (d, J¼5.9 Hz, 1H), 4.12 (q, J¼7.1 Hz, 1H),
3.89e3.74 (m, 2H), 3.70 (s, 3H), 1.29e1.23 (m, 1H), 1.03 (apparent t,
J¼7.0 Hz, 6H); 13C NMR (75 MHz, CDCl3):
d 152.8 (C), 140.3 (C), 115.2
(2ꢁ CH), 115.0 (2ꢁ CH), 76.5 (CH2), 58.9 (CH), 55.7 (CH3), 30.4 (CH),
19.0 (CH3), 18.1 (CH3); MS (ESIþ) m/z (%) 239 ([MþH]þ, 100), 232
(29), 208 (20), 176 (24); HRMS (ESIþ) calcd for [C12H19N2O3]þ
[MþH]þ 239.1396, found 239.1390; IR (neat): 3402, 1554, 1512,
1382, 1242 cmꢂ1; Rf¼0.53 (hexane/EtOAc 3:1).
2.1.4.3. 1-Cyclohexyl-2-nitro-N-tosylethanamine
(3c). Yellow
7.69 (d,
solid; mp 135e137 ꢀC; 1H NMR (300 MHz, CDCl3):
d
J¼8.1 Hz, 2H), 7.25 (d, J¼8.1 Hz, 2H), 5.21 (d, J¼9.2 Hz, 1H), 4.42 (dd,
J¼13.1, 5.2 Hz, 1H), 4.30 (dd, J¼13.1, 5.3 Hz, 1H), 3.60e3.52 (m, 1H),
2.73 (s, 3H), 1.70e1.34 (m, 5H), 1.15e0.68 (m, 6H); 13C NMR
2.1.4.9. 4-Methoxy-N-(3-methyl-1-nitropentan-2-yl)benzen-
(75 MHz, CDCl3):
d
143.9 (C), 137.1 (C), 129.7 (2ꢁ CH), 127.0 (2ꢁ CH),
amine (3i). Brown oil; 1HNMR (300 MHz, CDCl3):
d
6.76 (d, J¼9.1 Hz,
76.2 (CH), 56.4 (CH), 39.6 (CH), 29.2 (CH2), 28.4 (2ꢁ CH2), 25.6 (2ꢁ
CH2), 21.5 (CH3); MS (ESIþ) m/z (%) 327 ([MþH]þ, 64), 268 (6), 266
(100), 112 (4); HRMS (ESIþ) calcd for [C15H23N2O4S]þ [MþH]þ
327.1379, found 327.1373; IR (neat): 3259, 1556, 1385, 1266,
1162 cmꢂ1; Rf¼0.40 (hexane/EtOAc 3:1).
2H), 6.75 (d, J¼9.0 Hz, 2H), 6.65 (d, J¼9.0 Hz, 2H), 6.64 (d, J¼9.0 Hz,
2H), 4.70 (dd, J¼12.5, 1.7 Hz, 1H), 4.67 (dd, J¼12.3, 2.0 Hz, 1H), 4.45
(dd, J¼12.5, 1.8 Hz, 1H), 4.43 (dd, J¼12.3, 2.7 Hz, 1H), 4.15e4.05 (m,
2H), 3.72 (s, 6H), 1.74e1.48 (m, 2H), 1.28e1.23 (m, 4H), 1.20 (d,
J¼4.3 Hz, 6H), 0.95 (t, J¼7.2 Hz, 3H), 0.88 (t, J¼7.5 Hz, 3H); 13C NMR
(75 MHz, CDCl3):
d
152.6 (2ꢁ C), 140.9 (C), 140.7 (C), 114.9 (4ꢁ CH),
2.1.4.4. 1-Nitro-4-phenyl-N-tosylbutan-2-amine
(3d). Yellow
7.68 (d,
114.8 (4ꢁ CH), 76.1 (CH2), 75.9 (CH2), 75.1 (CH), 74.7 (CH), 55.6 (2ꢁ
CH3), 32.1 (CH), 32.0 (CH), 23.3 (CH2), 23.0 (CH2), 8.0 (2ꢁ CH3), 7.7
(2ꢁ CH3); MS (ESIþ) m/z (%) 275 ([MþNa]þ, 100), 270 ([MþNH4]þ,
47), 253 ([MþH]þ, 12), 209 (6), 206 (4); HRMS (ESIþ) calcd for
[C13H21N2O3]þ [MþH]þ 253.1552, found 253.1548; IR (neat): 3410,
1555, 1513, 1380, 1247 cmꢂ1; Rf¼0.53 (hexane/EtOAc 1:1).
solid; mp 136e138 ꢀC; 1H NMR (300 MHz, CDCl3):
d
J¼7.4 Hz, 2H), 7.25e7.09 (m, 5H), 6.89 (d, J¼7.4 Hz, 2H), 5.48 (d,
J¼8.8 Hz, 1H), 4.39 (dd, J¼12.9, 5.0 Hz, 2H), 4.30 (dd, J¼12.9, 5.2 Hz,
1H), 3.77e3.66 (m, 1H), 2.57e2.47 (m, 2H), 2.36 (s, 3H), 1.80e1.69
(m, 2H); 13C NMR (75 MHz, CDCl3):
d 144.0 (C), 139.7 (C), 136.9 (C),
129.9 (2ꢁ CH), 128.5 (2ꢁ CH), 128.1 (2ꢁ CH), 127.0 (2ꢁ CH), 126.2
(CH), 78.2 (CH2), 51.1 (CH), 33.9 (CH2), 31.4 (CH2), 21.4 (CH3); MS
(ESIþ) m/z (%) 349 ([MþH]þ,100), 288 (10), 214 (10),196 (7),149 (5);
HRMS (ESIþ) calcd for [C17H21N2O4S]þ [MþH]þ 349.1222, found
349.1217; IR (neat): 3273, 1558, 1381, 1334, 1160 cmꢂ1; Rf¼0.35
(hexane/EtOAc 3:1).
2.1.4.10. N-(1-Cyclohexyl-2-nitroethyl)-4-methoxybenzenamine
(3j). Brown oil; 1H NMR (300 MHz, CDCl3):
d
6.76 (d, J¼9.0 Hz, 2H),
6.65 (d, J¼9.0 Hz, 2H), 4.72 (dd, J¼12.3, 5.2 Hz, 1H), 4.46 (dd, J¼12.3,
7.4 Hz, 1H), 4.08e4.04 (m, 1H), 3.73 (s, 3H), 2.73 (s, 11H); 13C NMR
(75 MHz, CDCl3):
d
152.7 (C), 141.0 (C), 115.0 (2ꢁ CH), 114.9 (2ꢁ CH),
75.7 (CH2), 60.9 (CH), 55.7 (CH3), 43.0 (CH), 34.7 (2ꢁ CH2), 25.2
(CH2), 21.6 (2ꢁ CH2); MS (ESIþ) m/z (%) 279 ([MþH]þ, 6), 234 (19),
216 (100), 214 (28); HRMS (ESIþ) calcd for [C15H23N2O3]þ [MþH]þ
279.1709, found 279.1703; IR (neat): 3389, 1553, 1513, 1384,
1243 cmꢂ1; Rf¼0.22 (hexane/EtOAc 3:1).
2.1.4.5. 2-Nitro-1-phenyl-N-tosylethanamine (3e). Yellow solid;
mp 156e159 ꢀC; 1H NMR (300 MHz, CDCl3):
d
7.64 (d, J¼8.8 Hz, 2H),
7.25e7.20 (m, 5H), 7.09 (d, J¼8.8 Hz, 2H), 5.59 (d, J¼7.6 Hz, 1H), 5.00
(apparent q, J¼6.9 Hz, 1H), 4.82 (dd, J¼13.1, 6.7 Hz, 1H), 4.66 (dd,
J¼13.1, 6.3 Hz, 1H), 2.40 (s, 3H); 13C NMR (75 MHz, CDCl3):
d 143.9
(C), 136.4 (C), 135.2 (C), 129.7 (2ꢁ CH), 129.1 (2ꢁ CH), 128.9 (CH),
127.0 (2ꢁ CH), 126.4 (2ꢁ CH), 78.9 (CH2), 55.4 (CH), 21.5 (CH3); MS
(ESIþ) m/z (%) 343 ([MþNa]þ, 100), 338 ([MþNH4]þ, 42), 321
([MþH]þ, 4), 260 (7); HRMS (ESIþ) calcd for [C15H17N2O4S]þ
[MþH]þ 321.0909, found 321.0903; IR (neat): 3251, 1552, 1379,
1324, 1163 cmꢂ1; Rf¼0.60 (hexane/EtOAc 1:1).
2.1.4.11. 4-Methoxy-N-[(Z)-1-nitroundec-8-en-2-yl]benzenamine
(3k). Brown oil; 1H NMR (300 MHz, CDCl3):
d
6.80 (d, J¼7.2 Hz, 2H),
6.64 (d, J¼7.2 Hz, 2H), 6.51 (d, J¼7.1 Hz, 1H), 5.41e5.25 (m, 2H), 4.51
(dd, J¼11.4, 5.3 Hz, 1H), 4.41 (dd, J¼11.4, 5.4 Hz, 1H), 3.96e3.90 (m,
1H), 3.76 (s, 3H), 2.05e2.00 (m, 4H), 1.70e1.68 (m, 8H), 0.96 (t,
J¼7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 139.8 (C), 138.5 (C), 131.8
(CH), 128.8 (CH), 115.4 (2ꢁ CH), 115.1 (2ꢁ CH), 78.0 (CH2), 55.7
(CH3), 53.5 (CH), 32.8 (CH2), 29.4 (CH2), 28.9 (CH2), 26.8 (CH2), 25.8
(CH2), 20.5 (CH2), 14.3 (CH3); MS (ESIþ) m/z (%) 343 ([MþNa]þ, 100),
321 ([MþH]þ, 32), 301 (21), 274 (12), 213 (4); HRMS (ESIþ) calcd for
[C18H29N2O3]þ [MþH]þ 321.2178, found 321.2172; IR (neat): 3402,
1553, 1514, 1381, 1242 cmꢂ1; Rf¼0.53 (hexane/EtOAc 3:1).
2.1.4.6. 2-Nitro-1-p-cyanophenyl-N-tosylethanamine
(3f). Yellow solid; mp 160e162 ꢀC; 1H NMR (300 MHz, CDCl3):
d
7.69 (d, J¼8.0 Hz, 4H), 7.56 (d, J¼8.0 Hz, 4H), 5.55 (dd, J¼8.1,
3.9 Hz, 1H), 4.62e4.50 (m, 2H), 2.03 (s, 3H); 13C NMR (75 MHz,
CDCl3):
d
143.3 (2ꢁ C),132.7 (4ꢁ C),132.4 (C),126.7 (4ꢁ C),118.2 (C),
112.6 (C), 80.7 (CH2), 70.0 (CH), 21.0 (CH3); MS (ESIþ) m/z (%) 368
([MþNa]þ, 100), 346 ([MþH]þ, 12), 274 (6), 190 (5); HRMS (ESIþ)
calcd for [C16H16N3O4S]þ [MþH]þ 346.0862, found 346.0855; IR
(neat): 3449, 2232, 1558, 1378, 1266, 1163 cmꢂ1; Rf¼0.62 (hexane/
EtOAc 1:1).
2.1.4.12. 4-Methoxy-N-(2-nitro-1-phenylethyl)benzenamine
(3l). Brown oil; 1H NMR (300 MHz, CDCl3):
d 7.61e7.24 (m, 5H),
6.73 (d, J¼9.0 Hz, 2H), 6.58 (d, J¼9.0 Hz, 2H), 6.23 (d, J¼7.4 Hz, 1H),
5.09 (t, J¼6.7 Hz, 1H), 4.69 (d, J¼6.7 Hz, 2H), 3.71 (s, 3H); 13C NMR

H. Rodríguez-Solla et al. / Tetrahedron 68 (2012) 1736e1744
1741
(75 MHz, CDCl3):
d
153.1 (C), 139.6 (C), 137.9 (C), 129.2 (2ꢁ CH),
4.52e4.33 (s, 2H), 3.49e3.41 (m, 1H), 2.99 (dd, J¼13.6, 3.7 Hz, 1H),
2.72 (dd, J¼13.6, 8.4 Hz,1H), 2.42 (s, 3H),1.42e1.08 (m,12H), 0.85 (t,
128.5 (CH), 126.4 (2ꢁ CH), 115.6 (2ꢁ CH), 114.8 (2ꢁ CH), 80.0 (CH2),
57.7 (CH), 55.6 (CH3); MS (ESIþ) m/z (%) 273 ([MþH]þ, 4), 213 (7),
212 (100), 124 (7); HRMS (ESIþ) calcd for [C15H17N2O3]þ [MþH]þ
273.1239, found 273.1233; IR (neat): 3375, 1554, 1511, 1378,
1243 cmꢂ1; Rf¼0.23 (hexane/AcOEt 3:1).
J¼6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 143.3 (C), 137.8 (C), 129.6
(2ꢁ CH), 127.1 (2ꢁ CH), 51.7 (CH), 46.0 (CH2), 31.6 (CH2), 29.6 (CH2),
29.0 (CH2), 25.3 (CH2), 24.8 (CH2), 22.5 (CH2), 21.4 (CH), 14.0 (CH3);
MS (ESIþ) m/z (%) 313 ([MþH]þ, 100), 282 (2), 227 (1), 225 (8);
HRMS (ESIþ) calcd for [C16H29N2O2S]þ [MþH]þ 313.1950, found
313.1944; IR (neat): 3434, 1638, 1450, 1325, 1160 cmꢂ1; Rf¼0.26
(hexane/EtOAc 1:1).
2.1.4.13. 4-[1-(4-Methoxyphenylamino)-2-nitroethyl]benzonitrile
(3m). Brown oil; 1H NMR (300 MHz, CDCl3):
d
7.68 (d, J¼8.3 Hz,
2H), 7.53 (d, J¼8.3 Hz, 2H), 6.73 (d, J¼9.0 Hz, 2H), 6.53 (d,
J¼9.0 Hz, 2H), 5.12 (t, J¼6.4 Hz, 1H), 4.71 (d, J¼6.4 Hz, 2H), 3.71
2.1.5.2. 4-Phenyl-N2-tosylbutane-1,2-diamine (6b). Yellow oil;
(s, 3H); 13C NMR (75 MHz, CDCl3):
d
153.4 (C), 143.3 (C), 138.7
1H NMR (300 MHz, CDCl3):
d
7.71 (d, J¼7.7 Hz, 2H), 7.29e7.13 (m,
(C), 133.0 (2ꢁ CH), 129.3 (C), 127.4 (2ꢁ CH), 118.1 (C), 115.7 (2ꢁ
CH), 114.9 (2ꢁ CH), 79.5 (CH2), 57.3 (CH), 55.6 (CH3); MS (ESIþ)
m/z (%) 320 ([MþNa]þ, 100), 298 ([MþH]þ, 64), 212 (60), 186
(24); HRMS (ESIþ) calcd for [C16H16N3O3]þ [MþH]þ 298.1192,
found 298.1188; IR (neat): 3388, 2230, 1556, 1512, 1378, 1240,
cmꢂ1; Rf¼0.20 (hexane/AcOEt 3:1).
5H), 7.06 (d, J¼7.7 Hz, 2H); 6.46 (d, J¼6.0 Hz, 1H), 4.35e4.29 (m,
1H), 4.00e3.62 (m, 1H), 2.77e2.46 (m, 3H), 2.39 (s, 3H),
2.03e1.73 (m, 4H); 13C NMR (75 MHz, CDCl3):
d 143.3 (C), 140.8
(C), 137.2 (C), 129.5 (2ꢁ CH), 128.3 (2ꢁ CH), 127.1 (2ꢁ CH), 127.0
(2ꢁ CH), 125.9 (CH), 54.4 (CH), 46.09 (CH2), 30.9 (CH2), 25.0
(CH2), 21.4 (CH3); MS (ESIþ) m/z (%) 319 ([MþH]þ, 100), 288 (4),
164 (2) HRMS (ESIþ) calcd for [C17H23N2O2S]þ [MþH]þ 319.1480,
2.1.4.14. tert-Butyl 2-nitro-1-phenylethylcarbamate (3n). White
found 319.1489; IR (neat): 3407, 1634, 1454, 1331, 1160 cmꢂ1
;
solid; mp 101e103 ꢀC; 1H NMR (300 MHz, CDCl3):
d
7.43e7.29 (m,
5H), 5.37e5.28 (m, 2H), 4.84e4.82 (m, 1H), 4.70 (dd, J¼12.6, 5.6 Hz,
1H), 1.44 (s, 9H); 13C NMR (75 MHz, CDCl3):
154.7 (C), 136.9 (C),
Rf¼0.30 (hexane/EtOAc 1:1).
d
2.1.5.3. 1-Cyclohexyl-N1-tosylethane-1,2-diamine
oil; 1H NMR (300 MHz, CDCl3):
(6c). Yellow
7.77 (d, J¼8.0 Hz, 2H), 7.29 (d,
129.1 (2ꢁ CH), 128.6 (CH), 126.2 (2ꢁ CH), 80.6 (C), 78.8 (CH2), 55.8
(CH), 28.1 (3ꢁ CH3); MS (ESIþ) m/z (%) 289 ([MþNa]þ, 100), 233
(31), 150 (13), 102 (7); HRMS (ESIþ) calcd for [C13H18N2O4Na]þ
[MþNa]þ 289.1164, found 289.1161; IR (neat): 3330, 1716, 1557,
1380, 1266 cmꢂ1; Rf¼0.50 (hexane/AcOEt 3:1).
d
J¼8.0 Hz, 2H), 3.69 (t, J¼5.4 Hz, 1H), 3.08 (s, 2H), 2.74 (dd, J¼13.2,
6.0 Hz, 1H), 2.63 (dd, J¼13.2, 4.3 Hz, 1H), 2.42 (s, 3H), 2.03e0.75 (m,
11H); 13C NMR (75 MHz, CDCl3):
d
143.3 (C), 139.7 (C), 129.6 (2ꢁ
CH), 127.0 (2ꢁ CH), 59.7 (CH2), 41.8 (CH), 39.6 (CH), 29.6 (2ꢁ CH2),
29.3 (CH2), 29.0 (2ꢁ CH2), 21.5 (CH3); MS (ESIþ) m/z (%) 297
([MþH]þ, 100), 266 (4); HRMS (ESIþ) calcd for [C15H25N2O2S]þ
[MþH]þ 297.1637, found 297.1631; IR (neat): 3406, 1648, 1449,
1329, 1158 cmꢂ1; Rf¼0.28 (hexane/EtOAc 1:1).
2.1.4.15. tert-Butyl 1-(4-cyanophenyl)-2-nitroethylcarbamate
(3o). White solid; mp 100e102 ꢀC; 1H NMR (300 MHz, CDCl3):
d
7.67 (d, J¼7.3 Hz, 2H), 7.46 (d, J¼7.3 Hz, 2H), 5.86e5.61 (m, 1H),
5.51e5.32 (m, 1H), 4.84e4.74 (m, 2H), 1.41 (s, 9H); 13C NMR
(75 MHz, CDCl3):
d
154.6 (C), 142.3 (C), 132.8 (2ꢁ CH), 127.1 (2ꢁ CH),
2.1.6. Synthesis
of
2-amino-1-bromo-1-nitroalkanes
7. NaI
118.1 (C), 112.4 (C), 81.0 (C), 78.2 (CH2), 52.2 (CH), 28.1 (3ꢁ CH3); MS
(ESIþ) m/z (%) 314 ([MþNa]þ, 100), 285 (15), 210 (92), 131 (31), 110
(31); HRMS (ESIþ) calcd for [C14H18N3O4]þ [MþH]þ 292.1297, found
(0.12 mmol, 0.15 equiv) was added to a stirred solution of bromo-
nitromethane 2 (0.8 mmol, 1 equiv) and the corresponding imine 1
(0.8 mmol, 1 equiv) in THF (10 mL). After stirring the reaction
mixture at room temperature for 5 h it was quenched with aqueous
HCl (10 mL, 0.1 M) before the organic material was extracted with
diethyl ether. The combined extracts were washed with an aqueous
saturated solution of Na2S2O3 and then dried over Na2SO4 and the
solvent was removed under reduced pressure affording products 7.
Purification by column chromatography (hexane:EtOAc 3:1) was
only necessary when the imine used is aromatic 1nep.
292.1293; IR (neat): 3350, 2231, 1689, 1557, 1369, 1251 cmꢂ1
;
Rf¼0.30 (hexane/AcOEt 3:1).
2.1.4.16. tert-Butyl 1-(4-methoxyphenyl)-2-nitroethylcarbamate
(3p). Yellow solid; mp 101e103 ꢀC; 1H NMR (300 MHz, CDCl3):
d
7.15 (d, J¼8.8 Hz, 2H), 6.81 (d, J¼8.8 Hz, 2H), 5.37e5.15 (m, 2H),
4.84e4.67 (m, 1H), 4.60e4.56 (m, 1H), 3.71 (s, 3H), 1.35 (s, 9H); 13C
NMR (75 MHz, CDCl3):
d
159.6 (C), 154.7 (C), 128.8 (C), 127.5 (2ꢁ
CH), 114.4 (2ꢁ CH), 80.5 (C), 78.8 (CH2), 55.5 (CH3), 52.4 (CH), 28.1
(3ꢁ CH3); MS (ESIþ) m/z (%) 297 ([MþH]þ, 24), 293 (100), 187 (34),
171 (50), 127 (45), 113 (29); HRMS (ESIþ) calcd for [C14H20N2O5Na]þ
[MþNa]þ 319.1270, found 319.1279; IR (neat): 3327, 1677, 1557,
1370, 1266 cmꢂ1; Rf¼0.35 (hexane/AcOEt 3:1).
2.1.6.1. 1-Bromo-1-nitro-N-tosylnonan-2-amine
(7a). Yellow
7.71 (d,
solid; mp 138e142 ꢀC; 1H NMR (300 MHz, CDCl3):
d
J¼8.2 Hz, 2H), 7.69 (d, J¼8.1 Hz, 2H), 7.25 (d, J¼8.2 Hz, 2H), 7.24 (d,
J¼8.1 Hz, 2H), 6.14 (d, J¼4.3 Hz, 1H), 6.09 (d, J¼3.1 Hz, 1H), 5.81 (d,
J¼4.0 Hz,1H), 5.78 (d, J¼3.5 Hz,1H), 3.90e3.78 (m, 2H), 2.34 (s, 6H),
1.79e1.17 (m, 24H), 0.85e0.73 (m, 6H); 13C NMR (75 MHz, CDCl3):
2.1.5. Synthesis 1,2-diaminoalkanes 6. To a solution of SmI2 (0.1 M,
0.52 mmol, 10 equiv) in THF was added the sulphonamide
d
143.9 (C), 143.8 (C), 136.7 (C), 136.5 (C), 129.6 (2ꢁ CH), 129.5 (2ꢁ
CH), 126.9 (2ꢁ CH), 126.8 (2ꢁ CH), 85.2 (CH), 84.0 (CH), 57.6 (CH),
56.4 (CH), 31.2 (2ꢁ CH2), 30.8 (CH2), 29.7 (CH2), 28.5 (2ꢁ CH2), 28.4
(2ꢁ CH2), 25.0 (CH2), 24.3 (CH2), 22.2 (2ꢁ CH2), 21.2 (2ꢁ CH2), 13.7
(2ꢁ CH2); MS (ESIþ) m/z (%) 423 ([Mþ2þH]þ, 33), 421 ([MþH]þ, 31),
282 (100), 128 (37); HRMS (ESIþ) calcd for [C16H26BrN2O4S]þ
[MþH]þ 421.0797, found 421.0791; IR (neat): 3273, 1562, 1385,
1337, 1163, 815 cmꢂ1; Rf¼0.50 (hexane/EtOAc 3:1).
(0.052 mmol, 1 equiv) followed by water (28
mL, 1.56 mmol) and
pyrrolidine (90 L, 1.04 mmol) under a nitrogen atmosphere. The
m
reaction mixture immediately turned white upon addition of
amine. The resulting mixture was diluted with diethyl ether (4 mL)
and treated with a solution of potassium sodium tartrate and po-
tassium carbonate (10% w/w each). The aqueous phase was
extracted with two portions of diethyl ether. The organic extracts
were pooled, dried, and evaporated to yield the crude amine. An-
alytically pure compounds 6 were obtained being unnecessary
further purification.
2.1.6.2. 1-Bromo-3-methyl-1-nitro-N-tosylpentan-2-amine
(7b). Yellow solid; mp 140e143 ꢀC; 1H NMR (300 MHz, CDCl3):
d
7.83e7.60 (m, 8H), 7.35e7.18 (m, 8H), 6.04 (d, J¼2.6 Hz, 1H), 5.99
(d, J¼3.4 Hz, 1H), 5.97 (d, J¼4.6 Hz, 1H), 5.83 (d, J¼7.1 Hz, 1H),
5.28e4.90 (m, 4H), 4.16e3.94 (m, 4H), 2.34 (s, 12H), 1.88e1.72 (m,
2H), 1.71e1.68 (m, 2H), 1.48e1.06 (m, 8H), 0.93e0.69 (m, 24H); 13C
2.1.5.1. N2-Tosylnonane-1,2-diamine (6a). Yellow oil; 1H NMR
(300 MHz, CDCl3):
d
7.79 (d, J¼8.3 Hz, 2H), 7.30 (d, J¼8.3 Hz, 2H),

1742
H. Rodríguez-Solla et al. / Tetrahedron 68 (2012) 1736e1744
NMR (75 MHz, CDCl3):
d
143.7 (2ꢁ C), 143.6 (2ꢁ C), 137.6 (2ꢁ C),
HRMS (ESIþ) calcd for [C13H17BrN2O4Na]þ [MþNa]þ 367.0269,
137.4 (2ꢁ C),129.4 (8ꢁ CH),126.8 (8ꢁ CH), 85.3 (CH), 84.5 (CH), 81.9
(CH), 81.4 (CH), 61.8 (CH), 61.5 (CH), 61.1 (CH), 60.3 (CH), 38.4 (CH),
37.2 (CH), 36.6 (CH), 35.9 (CH), 26.3 (CH2), 25.9 (CH2), 24.4 (CH2),
23.5 (CH2), 21.3 (4ꢁ CH3), 15.2 (CH3), 15.1 (CH3), 14.3 (CH3), 13.1
(CH3), 11.2 (CH3), 10.8 (CH3), 10.7 (CH3), 10.3 (CH3); MS (ESIþ) m/z
(%) 381 ([Mþ2þH]þ, 26), 379 ([MþH]þ, 25), 240 (100), 214 (26), 149
(11), 122 (10); HRMS (ESIþ) calcd for [C13H20BrN2O4S]þ [MþH]þ
379.0327, found 379.0322; IR (neat): 3278, 1570, 1334, 1266, 1161,
739 cmꢂ1; Rf¼0.37 (hexane/EtOAc 3:1).
found 367.0277; IR (neat): 3375, 1682, 1563, 1366, 701 cmꢂ1
;
Rf¼0.50 (Hexane/EtOAc 3:1).
2.1.6.7. tert-Butyl 2-bromo-1-(4-cyanophenyl)-2-nitroethylcar-
bamate (7g). White solid; mp 100e102 ꢀC; 1H NMR (300 MHz,
CDCl3):
d
7.71 (d, J¼8.4 Hz, 2H), 7.69 (d, J¼8.4 Hz, 2H), 7.48 (d,
J¼8.4 Hz, 2H), 7.45 (d, J¼8.4 Hz, 2H), 6.33 (d, J¼7.1 Hz, 2H), 5.80 (d,
J¼9.2 Hz, 1H), 5.74e5.72 (m, 1H), 5.58e5.43 (m, 2H), 1.48 (s, 9H),
1.43 (s, 9H); 13C NMR (75 MHz, CDCl3):
d 154.5 (C), 154.2 (C), 140.4
(C), 139.8 (C), 132.8 (4ꢁ CH), 127.9 (2ꢁ CH), 127.6 (2ꢁ CH), 117.9 (2ꢁ
C),113.3 (C),113.1 (C), 84.2 (C), 81.6 (CH), 80.5 (2ꢁ CH), 57.7 (2ꢁ CH),
28.1 (6ꢁ CH3); MS (ESIþ) m/z (%) 372 ([Mþ2þH]þ, 22), 370
([MþH]þ, 100), 314 (54), 175 (9), 131 (15); HRMS (ESIþ) calcd
for [C14H17BrN3O4]þ [MþH]þ 370.0402, found 370.0404; IR (neat):
3419, 2231, 1689, 1558, 1368, 736 cmꢂ1; Rf¼0.38 (hexane/EtOAc
3:1).
2.1.6.3. 2-Bromo-1-cyclohexyl-2-nitro-N-tosylethanamine (7c).
Yellow solid; mp 137e140 ꢀC; 1H NMR (300 MHz, CDCl3):
d 7.69
(d, J¼8.3 Hz, 2H), 7.61 (d, J¼8.3 Hz, 2H), 7.26e7.20 (m, 4H), 6.04
(d, J¼2.6 Hz, 1H), 5.94 (d, J¼5.4 Hz, 1H), 4.95 (d, J¼8.8 Hz, 1H),
4.78 (d, J¼9.1 Hz, 1H), 4.11e4.04 (m, 1H), 3.97e3.89 (m, 1H), 2.37
(s, 6H), 1.86e1.37 (m, 10H), 1.19e0.78 (m, 12H); 13C NMR
(75 MHz, CDCl3):
d 143.8 (C), 143.6 (C), 137.7 (C), 137.3 (C), 129.5
(2ꢁ CH), 129.4 (2ꢁ CH), 126.9 (2ꢁ CH), 126.7 (2ꢁ CH), 85.1 (CH),
81.8 (CH), 62.3 (CH), 61.6 (CH), 41.2 (CH), 39.6 (CH), 29.6 (CH2),
29.5 (CH2), 28.8 (2ꢁ CH2), 27.4 (2ꢁ CH2), 25.6 (2ꢁ CH2), 25.4
(2ꢁ CH2), 21.4 (2ꢁ CH3); MS (ESIþ) m/z (%) 407 ([Mþ2þH]þ, 17),
405 ([MþH]þ, 17), 267 (6), 266 (100), 112 (16); HRMS (ESIþ)
calcd for [C15H22BrN2O4S]þ [MþH]þ 405.0484, found 405.0478;
2.1.6.8. tert-Butyl
carbamate (7h). White solid; mp 99e101 ꢀC; 1H NMR (300 MHz,
CDCl3):
7.15 (apparent t, J¼7.5 Hz, 4H), 6.80 (d, J¼7.5 Hz, 4H),
6.33e6.11 (m, 2H), 5.82e5.65 (m, 1H), 5.57e5.17 (m, 2H), 3.70 (s,
6H), 1.36 (s, 18H); 13C NMR (75 MHz, CDCl3):
2-bromo-1-(4-methoxyphenyl)-2-nitroethyl-
d
d
160.0 (2ꢁ C), 154.6
(C), 154.4 (C), 128.2 (2ꢁ CH), 128.0 (2ꢁ CH), 127.0 (C), 126.6 (C),
114.3 (4ꢁ CH), 84.8 (CH), 81.9 (CH), 80.8 (2ꢁ C), 57.7 (CH), 57.6
(CH), 55.2 (2ꢁ CH3), 28.01 (6ꢁ CH3); MS (ESIþ) m/z (%) 400
([Mþ2þNa]þ, 93), 398 ([MþNa]þ, 60), 319 (100), 258 (85), 180
(17); HRMS (ESIþ) calcd for [C14H19BrN2O5]þ [MþH]þ 375.0556,
IR (neat): 3256, 1566, 1330, 1265, 1157, 738 cmꢂ1
(hexane/EtOAc 3:1).
;
Rf¼0.40
2.1.6.4. 1-Bromo-1-nitro-4-phenyl-N-tosylbutan-2-amine (7d).
Yellow solid; mp 135e138 ꢀC; 1H NMR (300 MHz, CDCl3):
7.73 (d,
d
found 375.0550; IR (neat): 3375, 1682, 1562, 1367, 742 cmꢂ1
;
J¼8.0 Hz, 2H), 7.67 (d, J¼7.2 Hz, 2H), 7.33e7.04 (m, 10H), 6.91 (d,
J¼8.0 Hz, 2H), 6.85 (d, J¼7.2 Hz, 2H), 6.09 (d, J¼4.3 Hz, 1H), 6.02 (d,
J¼2.8 Hz, 1H), 5.37e5.18 (m, 2H), 3.96e3.85 (m, 2H), 2.60e2.46 (m,
2H), 2.39e2.26 (m, 2H), 2.37 (s, 6H), 2.11e2.00 (m, 1H), 1.94e1.65
Rf¼0.33 (hexane/EtOAc 3:1).
2.1.7. Synthesis of N-(p-methoxyphenyl)imines 10. The p-methox-
yphenylimines 10 were prepared in nearly quantitative yields by
stirring for 2 h a solution in CH2Cl2 of the corresponding aldehyde
(10 mmol, 1.0 equiv) with p-anisidine (10 mmol, 1.0 equiv) in the
presence of molecular sieves, at room temperature, for 16 h under
inert atmosphere. Imines 10 were obtained as brown oils, which
were utilised without further purification.
(m, 3H); 13C NMR (75 MHz, CDCl3):
d 144.2 (C), 144.1 (C), 139.4 (C),
139.2 (C), 136.6 (C), 136.5 (C), 129.8 (2ꢁ CH), 129.5 (2ꢁ CH), 128.3
(4ꢁ CH), 128.1 (2ꢁ CH), 128.0 (2ꢁ CH), 127 (2ꢁ CH), 126.9 (2ꢁ CH),
126.2 (CH), 126.1 (CH), 84.8 (CH), 83.7 (CH), 57.3 (CH), 56.2 (CH),
32.5 (CH2), 31.8 (CH), 31.3 (CH2), 30.7 (CH2), 21.4 (2ꢁ CH3); MS
(ESIþ) m/z (%) 429 ([Mþ2þH]þ, 100), 427 ([MþH]þ, 92), 359 (14),
134 (20), 288 (28), 134 (19), 117 (15); HRMS (ESIþ) calcd for
[C17H20BrN2O4S]þ [MþH]þ 427.0327, found 427.0322; IR (neat):
3055,1571,1352,1265,1165, 747 cmꢂ1; Rf¼0.29 (hexane/EtOAc 3:1).
2.1.7.1. 3-O-Benzyl-5-deoxy-1,2-O-isopropylidene-5-[(4-methox-
20
yphenyl)imino]-
a
-
D
-xylofuranose (10a). Orange oil;
[
a
]
ꢂ30.9
D
(c 0.7, CHCl3); 1H NMR (300 MHz, CDCl3):
d
7.85 (d, J¼5.2 Hz, 1H),
7.26e7.19 (m, 5H), 7.00 (d, J¼8.9 Hz, 2H), 6.79 (d, J¼8.9 Hz, 2H), 6.01
(d, J¼3.6 Hz, 1H), 4.82 (apparent t, J¼4.2 Hz, 1H), 4.60 (d, J¼3.6 Hz,
1H), 4.49 (d, J¼12,0 Hz, 1H), 4.41 (d, J¼12,0 Hz, 1H); 4.17 (d,
J¼3.3 Hz, 1H), 3.70 (s, 3H), 1.42 (s, 3H), 1.25 (s, 3H); 13C NMR
2.1.6.5. N-(2-Bromo-1-cyclohexyl-2-nitroethyl)-4-methox-
ybenzenamine (7e). Brown oil; 1H NMR (300 MHz, CDCl3):
d 6.71 (d,
J¼9.0 Hz, 2H), 6.63 (d, J¼9.0 Hz, 2H), 6.56 (d, J¼9.0 Hz, 2H), 6.48 (d,
J¼9.0 Hz, 2H), 6.20 (d, J¼3.2 Hz, 2H), 5.84 (d, J¼8.0 Hz, 2H),
4.01e3.95 (m, 2H), 3.64 (s, 3H), 3.63 (s, 3H), 1.95e0.76 (m, 22H); 13C
(75 MHz, CDCl3):
d 159.9 (CH), 158.4 (C), 143.6 (C), 137.0 (C), 128.3
(2ꢁ CH), 127.8 (CH), 127.4 (2ꢁ CH), 122.0 (2ꢁ CH), 114.2 (2ꢁ CH),
112.0 (C),105.6 (CH), 84.5 (CH), 82.6 (CH), 82.1 (CH), 72.2 (CH2), 55.3
(CH3), 26.7 (CH3), 26.2 (CH3); MS (ESIþ) m/z (%) 401 ([MþNH4]þ,
45), 384 ([MþH]þ, 100), 339 (10), 326 (6); HRMS (ESIþ) calcd for
[C22H26NO5]þ [MþH]þ 384.1811, found 384.1805; IR (neat): 3055,
1695, 1513, 1266 cmꢂ1; Rf¼0.50 (hexane/EtOAc 3:1).
NMR (75 MHz, CDCl3):
d 152.8 (C), 152.6 (C), 140.8 (C), 140.3 (C),
114.8 (4ꢁ CH), 114.6 (4ꢁ CH), 87.1 (CH), 81.3 (CH), 63.8 (CH), 63.0
(CH), 55.5 (2ꢁ CH3), 43.0 (CH), 39.5 (CH), 31.2 (CH2), 30.3 (CH2),
29.9 (CH2), 29.2 (CH2), 28.7 (CH2), 26.4 (CH2), 25.8 (CH2), 25.6 (CH2),
25.3 (CH2), 24.9 (CH2); MS (ESIþ) m/z (%) 359 ([Mþ2þH]þ, 10), 357
([MþH]þ, 27), 218 (100), 154 (12); HRMS (ESIþ) calcd for
[C15H22BrN2O3]þ [MþH]þ 357.0814, found 357.0810; IR (neat):
3340, 1552, 1514, 1380, 1265, 738 cmꢂ1; Rf¼0.30 (hexane/EtOAc
3:1).
2.1.7.2. 3-O-Methyl-5-deoxy-1,2-O-isopropylidene-5[(4-methox-
20
yphenyl)imino]-
a
-
D
-xylofuranose (10b). Orange oil;
[
a
]
þ5.7
D
(c 0.6, CHCl3); 1H NMR (300 MHz, CDCl3):
d
7.89 (d, J¼5.9 Hz, 1H),
7.07 (d, J¼8.8 Hz, 2H), 6.83 (d, J¼8.8 Hz, 2H), 6.00 (d, J¼3.6 Hz, 1H),
4.82 (dd, J¼5.2, 3.5 Hz, 1H), 4.61 (d, J¼3.7 Hz, 1H), 3.97 (d, J¼3.5 Hz,
1H), 3.74 (s, 3H), 3.33 (s, 3H), 1.47 (s, 3H), 1.29 (s, 3H); 13C NMR
2.1.6.6. tert-Butyl 2-bromo-2-nitro-1-phenylethylcarbamate
(7f). White solid; mp 102e104 ꢀC, 1H NMR (300 MHz, CDCl3):
d
7.56e6.09 (m, 10H), 6.24 (s, 2H), 5.71 (d, J¼9.3 Hz, 1H), 5.64e5.53
(m, 1H), 5.40e5.31 (m, 2H), 1.47 (s, 9H), 1.46 (s, 9H); 13C NMR
(75 MHz, CDCl3):
(75 MHz, CDCl3):
d
159.7 (CH), 158.4 (C), 143.6 (C), 122.0 (2ꢁ CH),
114.2 (2ꢁ CH), 112.0 (C), 105.5 (CH), 86.8 (CH), 82.0 (CH), 81.9 (CH),
58.1 (CH3), 55.3 (CH3), 26.7 (CH3), 26.2 (CH3); MS (ESIþ) m/z (%) 308
([MþH]þ, 61), 248 (29), 136 (100), 124 (89), 105 (30); HRMS (ESIþ)
calcd for [C16H22NO5]þ [MþH]þ 308.1498, found 308.1492; IR
(neat): 3054, 1652, 1506, 1247 cmꢂ1; Rf¼0.50 (hexane/EtOAc 3:1).
d
154.6 (C), 154.4 (C), 135.2 (C), 134.7 (C), 129.1 (2ꢁ
CH), 129.0 (4ꢁ CH), 126.9 (2ꢁ CH), 126.7 (2ꢁ CH), 85.1 (CH), 81.5
(CH), 81.1 (C), 80.9 (C), 58.1 (2ꢁ CH), 28.1 (6ꢁ CH3); MS (ESIþ) m/z
(%) 347 ([Mþ2þH]þ, 100), 345 ([MþH]þ, 87), 293 (41), 113 (14);

H. Rodríguez-Solla et al. / Tetrahedron 68 (2012) 1736e1744
1743
2.1.7.3. 1-O-tert-Butyldimethylsilyl-5-deoxy-2,3-O-iso-
minor isomer
d
153.1 (C),139.6 (C),115.6 (2ꢁ CH),114.9 (2ꢁ CH),111.8
propylidene-5[(4-methoxyphenyl)imino]-
a
-
D
-lyxofuranose
(C), 104.7 (CH), 84.3 (CH), 80.6 (CH), 79.2 (CH), 76.1 (CH2), 57.1 (CH3),
55.5 (CH3), 53.1 (CH), 26.7 (CH3), 26.1 (CH3); MS (ESIþ) m/z (%) 391
([MþNa]þ, 4), 369 ([MþH]þ, 100), 330 (6), 311 (8), 308 (5); HRMS
(ESIþ) calcd for [C17H25N2O7]þ [MþH]þ 369.1662, found 369.1656; IR
(neat): 3371, 1515, 1384, 1246 cmꢂ1; Rf¼0.50 (hexane/AcOEt 3:1).
20
(10c). Orange oil; [
CDCl3):
a
]
D
þ6.3 (c 0.6, CHCl3); 1H NMR (300 MHz,
d
7.85 (d, J¼5.3 Hz, 1H), 7.12 (d, J¼8.8 Hz, 2H), 6.86 (d,
J¼8.8 Hz, 2H), 5.45 (s, 1H), 4.99 (dd, J¼5.5, 4.2 Hz, 1H), 4.72 (ap-
parent t, J¼4.6 Hz, 1H), 4.60 (d, J¼5.7 Hz, 1H), 3.77 (s, 3H), 1.47 (s,
3H), 1.29 (s, 3H), 0.88 (s, 9H), 0.16 (s, 3H), 0.12 (s, 3H); 13C NMR
(75 MHz, CDCl3):
d
159.8 (CH), 158.3 (C), 143.9 (C), 122.1 (2ꢁ CH),
2.1.8.3. 1-O-tert-Butyldimethylsilyl-5,6-deoxy-2,3-di-O-iso-
114.1 (2ꢁ CH), 112.6 (C), 101.8 (CH), 86.8 (CH), 82.1 (CH), 81.3 (CH),
55.2 (CH3), 25.9 (CH3), 25.5 (3ꢁ CH3), 24.5 (CH3), 17.7 (C), ꢂ4.6
(CH3), ꢂ5.6 (CH3); MS (ESIþ) m/z (%) 430 ([MþNa]þ, 47), 408
([MþH]þ, 100), 301 (32), 109 (6); HRMS (ESIþ) calcd for
[C21H34NO5Si]þ [MþH]þ 408.2209, found 408.2206; IR (neat): 1652,
1510, 1242, 1082, 860, 840 cmꢂ1; Rf¼0.47 (hexane/EtOAc 1:1).
propylidene-5-p-methoxyphenylamino-6-nitro-
a-D-mannofuranose
(11c). Orange oil; 1H NMR (500 MHz, CDCl3): major isomer
d
6.80e6.77 (m, 4H), 5.29 (apparent s,1H), 4.83 (dd, J¼3.5, 2.2 Hz,1H);
4.72 (dd, J¼8.0, 2.5 Hz,1H), 4.57e4.52 (m, 1H), 4.53 (dd, J¼5.1, 3.5 Hz,
1H), 4.40e4.36 (m,1H), 4.18 (dd, J¼4.5, 2.1 Hz,1H), 3.75 (s, 3H),1.51 (s,
3H), 1.31 (s, 3H), 0.86 (s, 9H), 0.11 (s, 3H), 0.07 (s, 3H); minor isomer
d
6.73e6.68 (m, 4H), 5.33 (apparent s, 1H), 4.82e4.78 (m, 1H); 4.69
2.1. 7. 4. 6-Deoxy-1, 2:3, 4-di-O-isopropylidene-6[(4-
(dd, J¼7.6, 4.0 Hz, 1H), 4.60 (dd, J¼8.0, 3.2 Hz, 1H), 4.58e4.52 (m,1H),
4.40e4.36(m,1H), 4.33 (dd, J¼3.9, 2.2 Hz,1H), 3.75 (s, 3H),1.48 (s, 3H),
1.31 (s, 3H), 0.87 (s, 9H), 0.10 (s, 3H), 0.07 (s, 3H); 13C NMR (125 MHz,
20
methoxyphenyl)imino]-a-D-galactopyranose (10d). Orange oil; [a]
D
þ7.2 (c 0.6, CHCl3); 1H NMR (300 MHz, CDCl3):
7.75 (d, J¼4.0 Hz,1H),
d
7.03 (d, J¼8.6 Hz, 2H), 6.78 (d, J¼8.6 Hz, 2H), 5.56 (d, J¼4.9 Hz,1H),4.58
(dd, J¼7.7, 2.3 Hz, 1H), 4.45e4.22 (m, 2H), 4.28 (dd, J¼5.0, 2.4 Hz, 1H),
3.69 (s, 3H), 1.48 (s, 3H), 1.39 (s, 3H),1.26 (s, 3H),1.24 (s, 3H); 13C NMR
CDCl3): major isomer
d
153.1 (C), 139.3 (C), 116.5 (2ꢁ CH), 115.2 (CH),
114.6 (2ꢁ CH), 112.2 (C), 101.0 (CH), 86.6 (CH), 79.4 (CH), 75.2 (CH2),
55.2 (CH3), 52.5 (CH), 25.7 (CH3), 25.3 (3ꢁ CH3), 24.3 (CH3), 17.5 (C),
(75 MHz, CDCl3):
d
160.9 (CH),158.1 (C),143.7 (C),121.8 (2ꢁ CH),113.9
ꢂ4.8 (CH3), ꢂ5.8 (CH3); minor isomer; 152.8 (C),139.7 (C),116.5 (2ꢁ
d
(2ꢁ CH),109.2 (C),108.5 (C), 96.0 (CH), 73.1 (CH), 70.3 (CH), 70.2 (CH),
55.1 (CH3), 53.2 (CH), 25.8(CH3), 25.7 (CH3), 24.6 (CH3), 24.0 (CH3); MS
(ESIþ) m/z (%) 364 ([MþH]þ, 100), 338 (7), 322 (30), 306 (4); HRMS
(ESIþ) calcd for [C19H26NO6]þ [MþH]þ 364.1760, found 364.1755; IR
(neat): 3060, 1674, 1510, 1260 cmꢂ1; Rf¼0.62 (hexane/EtOAc 3:1).
CH), 115.2 (CH), 114.6 (2ꢁ CH), 112.4 (C), 101.0 (CH), 79.0 (CH), 78.0
(CH), 76.1 (CH2), 55.2 (CH3), 53.0 (CH), 25.5 (CH3), 25.3 (3ꢁ CH3), 23.9
(CH3), 17.5 (C), ꢂ4.7 (CH3), ꢂ5.7 (CH3); MS (ESIþ) m/z (%) 491
([MþNa]þ, 2), 469 ([MþH]þ,100), 408 (13), 337 (9);HRMS (ESIþ)calcd
for [C22H37N2O7Si]þ [MþH]þ 469.2370, found 469.2365; IR (neat):
3385, 1555, 1515, 1377, 1242 cmꢂ1; Rf¼0.53 (hexane/AcOEt 3:1).
2.1.8. Synthesis of 2-amino-1-nitroalkanes 11. SmI2 or SmI3
(0.8 mmol, 1 equiv) in THF (8 mL) was added to a stirred solution of
bromonitromethane 2 (0.8 mmol, 1 equiv) and the corresponding
imines 10 (0.8 mmol, 1 equiv) in THF (5 mL). After stirring the re-
action mixture at room temperature for 5 h it was quenched with
aqueous HCl (10 mL, 0.1 M) and then, the organic material was
extracted with dichloromethane. The combined extracts were
washed with an aqueous saturated solution of Na2S2O3, then dried
over Na2SO4 and the solvents were removed under reduced pres-
sure affording compounds 11, which were purified by column
chromatography (hexane:EtOAc 3:1).
2.1.8.4. 6,7-Dideoxy-1,2:3,4-di-O-isopropylidene-6-p-methox-
yphenylamino-7-nitro-D-glycero-
b
-
D
-galacto-heptose (11d). Orange
oil; 1H NMR (300 MHz, CDCl3): major isomer
d
6.79e6.75 (m, 2H),
6.73e6.66 (m, 2H), 5.53 (d, J¼3.0 Hz,1H), 4.87 (dd, J¼8.1, 2.3 Hz,1H),
4.61e4.59 (m, 1H), 4.59e4.57 (m, 1H), 4.37 (dd, J¼4.9, 1.1 Hz, 1H);
4.29 (dd, J¼3.3, 1.8 Hz, 1H), 4.27 (dd, J¼2.8, 2.0 Hz, 1H), 3.95 (dd,
J¼3.6, 1.0 Hz, 1H), 3.73 (s, 3H), 1.47 (s, 3H), 1.33 (s, 3H), 1.31 (s, 3H),
1.29 (s, 3H); minor isomer
d 6.79e6.78 (m, 2H), 6.72e6.65 (m, 2H),
5.56 (d, J¼3.0 Hz, 1H), 4.81 (dd, J¼8.1, 3.1 Hz, 1H), 4.67 (dd, J¼7.8,
4.3 Hz, 1H), 4.59e4.57 (m, 1H), 4.43e4.40 (m, 1H), 4.35 (dd, J¼4.7,
1.0 Hz, 1H), 4.32 (dd, J¼3.0, 1.4 Hz, 1H), 4.12 (dd, J¼2.9, 1.7 Hz, 1H),
3.74 (s, 3H),1.46 (s, 3H),1.33 (s, 3H),1.32 (s, 3H),1.29 (s, 3H); 13C NMR
2.1.8.1. 3-O-Benzyl-5,6-dideoxy-1,2-O-isopropylidene-5-p-me-
27
thoxyphenylamino-6-nitro-
a
-
D
-glucofuranose (11a). Yellow oil; [
a
]
(75 MHz, CDCl3): major isomer
d
153.5 (C), 139.8 (C), 117.0 (2ꢁ CH),
D
ꢂ9.2 (c 0.6, CHCl3); 1H NMR (500 MHz, CDCl3):
d
7.34e7.12 (m, 5H),
114.9 (2ꢁ CH), 109.4 (C), 108.8 (C), 96.3 (CH), 75.1 (CH2), 71.1 (CH),
6.54 (d, J¼9.0 Hz, 2H), 6.34 (d, J¼9.0 Hz, 2H), 5.83 (d, J¼3.6 Hz, 1H),
4.67 (dd, J¼13.1, 3.9 Hz, 1H), 4.59e4.44 (m, 3H), 4.42e4.38 (m, 1H),
4.24e4.17 (m, 3H), 4.02 (d, J¼3.1 Hz,1H), 3.73 (s, 3H),1.47 (s, 3H); 1.31
70.9 (CH), 70.7 (CH), 67.0 (CH), 55.6 (CH3), 54.6 (CH), 25.8 (CH3), 25.7
(CH3), 24.8 (CH3), 24.0 (CH3); minor isomer;
d 153.0 (C), 139.9 (C),
115.1 (2ꢁ CH), 115.0 (2ꢁ CH), 109.6 (C), 108.9 (C), 96.5 (CH), 76.0
(CH2), 70.9 (2ꢁ CH), 70.4 (CH), 65.4 (CH), 55.6 (CH3), 54.8 (CH), 25.8
(2ꢁ CH3), 24.8 (CH3), 24.0 (CH3); MS (ESIþ) m/z (%) 447 ([MþNa]þ, 5),
424 ([MþH]þ, 100), 386 (22), 364 (26); HRMS (ESIþ) calcd for
[C20H29N2O8]þ [MþH]þ 425.1924, found 425.1918; IR (neat): 3366,
1552, 1511, 1381, 1237 cmꢂ1; Rf¼0.46 (hexane/AcOEt 3:1).
(s, 3H); 13C NMR (125 MHz, CDCl3):
d 153.3 (C), 139.3 (C), 136.9 (C),
128.4 (2ꢁ CH),128.0 (CH),127.9 (2ꢁ CH),116.3 (2ꢁ CH),114.9 (2ꢁ CH),
112.1 (C), 104.9 (CH), 81.9 (CH), 81.2 (CH), 79.9 (CH), 75.8 (CH2), 72.1
(CH2), 55.6 (CH3), 51.9 (CH), 26.7 (CH3), 26.2 (CH3); MS (ESIþ) m/z (%)
445 ([MþH]þ, 100), 444 (1), 316 (5), 289 (1), 288 (21); HRMS (ESIþ)
calcd for [C23H29N2O7]þ [MþH]þ 445.1975, found 445.1969; IR (neat):
3380, 1556, 1513, 1377, 1241 cmꢂ1; Rf¼0.28 (hexane/AcOEt 3:1).
2.1.9. Synthesis
of
2-amino-1-bromo-1-nitroalkanes
12. NaI
(0.12 mmol, 0.15 equiv) was added to a stirred solution of bromo-
nitromethane 2 (0.8 mmol, 1 equiv) and the corresponding imines
10 (0.8 mmol, 1 equiv) in THF (10 mL). After stirring the reaction
mixture at room temperature for 5 h it was quenched with aqueous
HCl (10 mL, 0.1 M) before the organic material was extracted with
diethyl ether. The combined extracts were washed with an aqueous
saturated solution of Na2S2O3 and then dried over Na2SO4 and the
solvent was removed under reduced pressure. Purification by col-
umn chromatography (hexane/EtOAc 3:1) afforded compounds 12
as a mixture of stereoisomers.
2.1.8.2. 3-O-Methyl-5,6-dideoxy-1,2-O-isopropylidene-5-p-me-
thoxyphenylamino-6-nitro-
NMR (300 MHz, CDCl3): major isomer
a-D
-glucofuranose (11b). Orange oil; 1H
d
6.79e6.73 (m, 4H), 5.86 (d,
J¼3.6 Hz, 1H), 4.74 (dd, J¼13.2, 4.0 Hz, 1H), 4.60e4.51 (m, 3H),
4.44e4.36 (m, 1H), 4.19 (dd, J¼8.1, 3.0 Hz,1H), 3.85 (d, J¼4.0 Hz,1H),
3.74 (s, 3H), 3.19 (s, 3H), 1.48 (s, 3H), 1.33 (s, 3H); minor isomer
6.70e6.67 (m, 4H), 5.91 (d, J¼3.8 Hz, 1H), 4.68e4.63 (m, 1H),
4.49e4.45(m, 3H), 4.44e4.36(m,1H), 4.14e4.07 (m,1H), 3.75 (s, 3H),
3.72 (d, J¼2.9 Hz, 1H), 3.39 (s, 3H), 1.52 (s, 3H), 1.35 (s, 3H); 13C NMR
(75 MHz, CDCl3): major isomer
d
153.2 (C), 139.5 (C), 116.3 (2ꢁ CH),
114.7 (2ꢁ CH), 111.9 (C), 104.8 (CH), 83.1 (CH), 81.2 (CH), 80.0 (CH),
2.1.9.1. (6R)-3-O-Benzyl-6-bromo-5,6-dideoxy-1,2-O-iso-
propylidene-5-p-methoxyphenylamino-6-nitro-a-D-glucofuranose
76.2 (CH2), 57.4 (CH3), 55.5 (CH3), 52.1 (CH), 26.7 (CH3), 26.1 (CH3);

1744
H. Rodríguez-Solla et al. / Tetrahedron 68 (2012) 1736e1744
27
(12a). White solid; mp 100e101 ꢀC; [
a
]
D
ꢂ41.1 (c 0.9, CHCl3); 1H
ꢀ
ꢀ
3. García Ruano, J. L.; Lopez-Cantarero, J.; de Haro, T.; Aleman, J.; Cid, M. B. Tet-
rahedron 2006, 62, 12197e12203.
NMR (500 MHz, CDCl3): d 7.29e7.27 (m, 3H), 7.14e7.11 (m, 2H), 6.59
4. Czekelius, C.; Carreira, E. M. Angew. Chem., Int. Ed. 2005, 44, 612e615.
5. (a) Lambert, A.; Rose, J. D. J. Chem. Soc. 1947, 1511e1513; (b) Senkus, M. J. Am.
Chem. Soc. 1946, 68, 10e12; (c) Jonhson, H. G. J. Am. Chem. Soc. 1946, 68, 12e14;
(d) Jonhson, H. G. J. Am. Chem. Soc. 1946, 68, 14e18.
6. (a) Henry, L. Bull. Cl. Sci., Acad. R. Belg. 1896, 32e33; (b) For a recent review, see:
Marques-Lopez, E.; Merino, P.; Tejero, T.; Herrera, R. P. Eur. J. Org. Chem. 2009,
(s, 4H), 6.49 (d, J¼2.2 Hz, 1H), 5.90 (d, J¼3.5 Hz, 1H), 4.91e4.88 (m,
1H), 4.54 (d, J¼3.5 Hz, 1H), 4.34 (d, J¼11.5 Hz, 1H), 4.14e4.04 (m,
2H), 4.02 (d, J¼11.5 Hz, 1H), 3.94 (d, J¼3.0 Hz, 1H), 3.66 (s, 3H), 1.49
(s, 3H), 1.30 (s, 3H); 13C NMR (125 MHz, CDCl3)
d 153.4 (C), 138.7 (C),
ꢀ
ꢀ
2401e2420.
136.9 (C), 128.7 (CH), 128.3 (2ꢁ CH), 127.9 (2ꢁ CH), 116.2 (2ꢁ CH),
114.7 (2ꢁ CH), 112.5 (C), 105.3 (CH), 88.0 (CH), 81.6 (CH), 81.3 (CH),
80.7 (CH), 72.5 (CH2), 56.9 (CH), 55.6 (CH3), 27.0 (CH3), 26.3 (CH3);
MS (ESIþ) m/z (%) 525 ([Mþ2þH]þ, 91), 523 ([MþH]þ, 100), 441
(39), 406 (72), 384 (26); HRMS (ESIþ) calcd for [C23H28BrN2O7]þ
[MþH]þ 523.1080, found 523.1074; IR (neat): 3397,1558,1513,1383,
1242, 736 cmꢂ1; Rf¼0.32 (hexane/EtOAc 3:1).
7. Adams, H.; Anderson, J. C.; Peace, S.; Pennell, A. M. K. J. Org. Chem. 1998, 63,
9932e9934.
8. Yamada, K.; Harwood, S. J.; Groger, H.; Shibasaki, M. Angew. Chem., Int. Ed. 1999,
€
38, 3504e3506.
9. (a) Anderson, J. C.; Blake, A. J.; Howel, G. P.; Ilson, C. W. J. Org. Chem. 2005, 70,
549e555; (b) Bernardi, L.; Bonini, B. F.; Capito, E.; Dessole, G.; Comes-Franchini,
M.; Fochi, M.; Ricci, A. J. Org. Chem. 2004, 69, 8168e8171.
10. Bifunctional thioureas: (a) Okino, T.; Nakamura, S.; Furukawa, T.; Takemoto, Y.
Org. Lett. 2004, 6, 625e627; (b) Xu, X.; Furukawa, T.; Okino, T.; Miyabe, H.;
Takemoto, Y. Chem.dEur. J. 2006, 12, 466e476; (c) Yoon, T. P.; Jacobsen, E. N.
Angew. Chem., Int. Ed. 2005, 44, 466e468 Alkaloids: (d) Bernardi, L.; Fini, F.;
ꢀ
2.1.9.2. 6-Bromo-1-O-tert-butyldimethylsilyl-5,6-deoxy-2,3-di-O-
isopropylidene-5-p-methoxyphenylamino-6-nitro-
a
-
D
-mannofur-
ꢀ
Herrera, R. P.; Ricci, A.; Sgarzani, V. Tetrahedron 2006, 62, 375e380; (e) Gomez-
anose (12b). Brown oil; 1H NMR (300 MHz, CDCl3):
d
major isomer
ꢀ
ꢀ
Bengoa, E.; Linden, A.; Lopez, R.; Mugica-Mendiola, I.; Oiarbide, M.; Palomo, C. J.
Am. Chem. Soc. 2008, 130, 7955e7966 N-Sulfinyl ureas: (f) Robak, M. T.; Trin-
cado, M.; Ellman, J. A. J. Chem. Soc. 2007, 15110e15111.
6.84e6.69 (m, 4H), 6.47 (d, J¼1.8 Hz, 1H), 5.97 (d, J¼5.4 Hz,1H), 5.33
(s, 1H), 4.83 (dd, J¼3.2, 2.5 Hz, 2H), 4.54 (dd, J¼6.3, 3.5 Hz, 1H), 4.19
(dd, J¼5.0, 2.4 Hz, 1H), 3.72 (s, 3H), 1.58 (s, 3H), 1.30 (s, 3H), 0.89 (s,
9H), 0.12(s, 3H), 0.11(s, 3H);minorisomer6.84e6.69(m, 4H), 6.22(d,
J¼2.2 Hz, 1H), 6.07 (d, J¼4.0 Hz, 1H), 5.25 (s, 1H), 4.90 (dd, J¼5.6,
1.1 Hz, 1H), 4.86 (dd, J¼3.4, 2.2 Hz, 1H), 4.60 (apparent t, J¼3.7 Hz,
1H), 3.94 (dd, J¼5.7, 2.2 Hz, 1H), 3.76 (s, 3H), 1.54 (s, 3H), 1.31 (s, 3H),
0.87 (s, 9H), 0.10 (s, 3H), 0.09 (s, 3H); 13C NMR (75 MHz, CDCl3): major
11. Yamada, K.; Moll, G.; Shibasaki, M. Synlett 2001, 980e982.
12. (a) Knudsen, K. R.; Risgaard, T.; Nishiwaki, N.; Gothelf, K. V.; Jørgensen, K. A. J.
Am. Chem. Soc. 2001, 123, 5843e5844; (b) Nishiwaki, N.; Knudsen, K. R.;
Gothelf, K. V.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2001, 40, 2992e2995; (c)
Knudsen, K. R.; Jørgensen, K. A. Org. Biomol. Chem. 2005, 3, 1362e1364; (d)
Handa, S.; Gnanadeskian, V.; Matsunaga, S.; Shibasaki, M. J. Am. Chem. Soc.
2007, 129, 4900e4901; (e) Zhou, H.; Peng, D.; Qin, B.; Hou, Z.; Liu, X.; Feng, X. J.
Org. Chem. 2007, 72, 10302e10304; (f) Tan, C.; Liu, X.; Wang, L.; Wang, J.; Feng,
X. Org. Lett. 2008, 10, 5305e5308; (g) Handa, S.; Gnanadesikan, V.; Matsunaga,
S.; Shibasaki, M. J. Am. Chem. Soc. 2010, 132 4925e2934.
isomer
d
153.5 (C), 138.8 (C), 116.6 (2ꢁ CH), 114.5 (2ꢁ CH), 112.7 (C),
ꢀ
13. (a) Palomo, C.; Oiarbide, M.; Halder, R.; Laso, A.; Lopez, R. Angew. Chem., Int. Ed.
101.4 (CH), 87.8 (CH), 86.6 (CH), 79.9 (CH), 79.2 (CH), 57.7 (CH), 55.5
2006, 45, 117e120; (b) Trost, B. M.; Lupton, D. W. Org. Lett. 2007, 9, 2023e2026.
(CH3), 26.1 (CH3), 25.5 (3ꢁ CH3), 24.7 (CH3), 17.8 (C), ꢂ4.3 (CH3), ꢂ5.8
ꢀ
ꢀ
14. Concellon, J. M.; Rodríguez-Solla, H.; Concellon, C. J. Org. Chem. 2006, 71,
(CH3); minor isomer
d
153.6 (C), 139.1 (C), 116.5 (2ꢁ CH), 114.9 (2ꢁ
7919e7922.
ꢀ
ꢀ
15. Concellon, J. M.; Rodríguez-Solla, H.; Concellon, C. Org. Lett. 2006, 8,
5979e5982.
CH), 112.8 (C), 100.9 (CH), 87.0 (CH), 86.5 (CH), 80.2 (CH), 79.0 (CH),
57.7 (CH), 55.5 (CH3), 26.1 (CH3), 25.5 (3ꢁ CH3), 24.7 (CH3), 17.8 (C),
ꢂ4.6 (CH3), ꢂ5.5 (CH3); MS (ESIþ) m/z (%) 549 ([Mþ2þH]þ,100), 547
([MþH]þ, 85), 441 (42), 430 (26), 108 (14); HRMS (ESIþ) calcd for
[C22H36BrN2O7Si]þ [MþH]þ 547.1475, found 547.1470; IR (neat):
3400,1560, 1515, 1378,1246, 741 cmꢂ1; Rf¼0.32 (hexane/EtOAc 3:1).
16. Wang, Y.; Song, J.; Hong, R.; Li, H.; Deng, L. J. Am. Chem. Soc. 2006,128, 8156e8157.
ꢀ
17. Concellon, J. M.; Rodríguez-Solla, H.; Bardales, E.; Huerta, M. Eur. J. Org. Chem.
2003, 1775e1778.
ꢀ
ꢀ
18. (a) Concellon, J. M.; Bardales, E.; Concellon, C.; García-Granda, S.; Rosario Díaz,
ꢀ
M. J. Org. Chem. 2004, 69, 6923e6926; (b) Concellon, J. M.; Bernad, P. L.; Bar-
dales, E. Chem.dEur. J. 2004, 10, 2445e2450; (c) Kwon, D. W.; Kim, Y. H.; Lee, K.
J. Org. Chem. 2002, 67, 9488e9491.
19. Ankner, T.; Hilmersson, G. Org. Lett. 2009, 11, 503e506.
Acknowledgements
20. To see other samarium-mediated nitro reductions see: (a) Basu, M. K.; Becker,
F. F.; Banik, B. K. Tetrahedron Lett. 2000, 41, 5603e5606; (b) Banik, B. K.; Mu-
khopadhyay, C.; Venkatraman, M. S.; Becker, F. F. Tetrahedron Lett. 1998, 39,
7243e7246; (c) Kende, A. S.; Mendoza, J. S. Tetrahedron Lett. 1991, 32,
1699e1702.
21. Hasegawa, M.; Taniyama, D.; Tomioka, K. Tetrahedron 2000, 56, 10153e10158.
22. Yan, S.; Klemm, D. Tetrahedron 2002, 58, 10065e10071.
We thank the MICINN (CTQ2010-14959 and CTQ2008-06493)
for financial support. C.C.F. thanks MICINN for a Juan de la Cierva
contract and N.A. thanks the Principado de Asturias for a pre-
doctoral fellowship.
23. CCDC 833254 contains the supplementary crystallographic data for compound
12a. This data can be obtained free of charge via: www.ccdc.cam.ac.uk/conts/
retrieving.html (or the Cambridge Data Center, 12 Union Road, Cambridge CB2
1EZ, UK; fax (þ44)1223-336-033; or deposit@ccdc.cam.ac.uk).
References and notes
24. A similar model has been used to explain the stereoselectivity observed in the
1. (a) Lucet, D.; Le Gall, T.; Mioskowski, C. Angew. Chem., Int. Ed. 1998, 37,
2580e2627; (b) Westermann, B. Angew. Chem., Int. Ed. 2003, 42, 151e153.
2. Ballini, R.; Petrini, M. Tetrahedron 2004, 60, 1017e1047.
addition of the nitronate and bromonitronate anions to
and 15, respectively).
L-alaninal (see Refs. 14