Chemoselective SN2′ reaction of nitroalkanes to dialkyl 2-(bromomethyl)fumarates under cetyltrimethylammonium hydroxide (CTAOH) catalysis

Article abstract of DOI:10.1016/j.tetlet.2009.12.122

The chemoselective S_N2′ reaction of a variety of primary nitroalkanes to dialkyl 2-(bromomethyl)fumarates can be efficiently performed under cetyltrimethylammonium hydroxide (CTAOH) catalysis. The α,β-unsaturated esters were obtained in satisfactory to good yields with the complete retention of the nitro group.

Full text of DOI:10.1016/j.tetlet.2009.12.122

Tetrahedron Letters 51 (2010) 1233–1235
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Chemoselective SN20 reaction of nitroalkanes to dialkyl
2-(bromomethyl)fumarates under cetyltrimethylammonium hydroxide
(CTAOH) catalysis
*
Roberto Ballini , Serena Gabrielli, Alessandro Palmieri
Green Chemistry Group, Dipartimento di Scienze Chimiche dell’Università di Camerino, Via S. Agostino 1, I-62032 Camerino (MC), Italy
a r t i c l e i n f o
a b s t r a c t
The chemoselective SN20 reaction of a variety of primary nitroalkanes to dialkyl 2-(bromomethyl)fuma-
rates can be efficiently performed under cetyltrimethylammonium hydroxide (CTAOH) catalysis. The
Article history:
Received 6 November 2009
Revised 17 December 2009
Accepted 21 December 2009
Available online 28 December 2009
a,b-unsaturated esters were obtained in satisfactory to good yields with the complete retention of the
nitro group.
Ó 2009 Elsevier Ltd. All rights reserved.
Dedicated to our mentor, Prof. Goffredo
Rosini, on the occasion of his 70th birthday
Keywords:
Nitroalkanes
CTAOH
Chemoselective SN20 reaction
a,b-Unsaturated esters
c
-Lactame
Nitroalkanes are powerful source of stabilized carbanions prone
Recently, we developed a new method for the conjugate addi-
tion of nitroalkanes to standard electrophilic alkenes under cetyl-
trimethylammonium hydroxide (CTAOH, 10% water solution)
catalysis.6 The procedure was very efficient and the mild reaction
conditions assure high chemoselectivity of the method. Now we
have found that CTAOH can be efficiently applied in the chemose-
lective SN20 reaction of nitroalkanes with bromomethylfumarate,
with the complete retention of the nitro group.
The efficiency of CTAOH was compared with other basic cata-
lysts and, with this purpose, we selected the reaction of 1-nitr-
opentane 1b with dimethyl 2-(bromomethyl)fumarate 2a as
sample reaction (Table 1).
to give the generation of new C,C bond mainly by the conjugate
addition to electron-poor alkenes (Michael reaction)1 or by the
nitroaldol (Henry) reaction with carbonyl derivatives.2 In this con-
text, the nucleophilic substitution reactions of halides with nitro-
alkanes are less exploited because it works well just with
particular substrates in which the electrophilic carbon is activated
by an electron-withdrawing group.3 Few years ago, Amri and co-
workers reported4 an interesting reaction of simple primary nitro-
alkanes (nitroethane and 1-nitropropane, Scheme 1) 1 with dialkyl
2-(bromomethyl)fumarate 2,5 under NaOH catalysis, with the
simultaneous elimination of both bromhydric and nitrous acids
(favored by the presence of an acidic hydrogen in
respect to the ester in the adduct 3) and the consequent formation
of conjugated dienes 4.
However, in spite of the great utility of the obtained dienes 4,
the elimination of the nitro group and the formation of the diene,
represent an important loss in terms of further chances, from syn-
thetic point of view, due to the possible conversion of the nitro
group into a variety of other useful functionalities. Thus, a new,
chemoselective catalytic procedure for the reaction of 1 to 2, pre-
serving the presence of the nitro group would be highly welcome.
a
-position with
It is evident that considering: (i) yield, (ii) reaction time, and
(iii) amount of catalyst the use of CTAOH is strongly preferred.
The reaction was performed by the addition of the catalyst
(0.625 mmol, 0.950 mL of CTAOH, 10% water solution) to a stirred
NO2
0.5 N NaOH
THF
MeO2C
Br
H
NO2
MeO2C
MeO2C
R
R
+
R
CO2Me
CO2Me
CO2Me
2
1
3
4
R = Me, Et
* Corresponding author. Tel.: +39 0737 402270; fax: +39 0737 402297.
E-mail address: roberto.ballini@unicam.it (R. Ballini).
Scheme 1. One-pot synthesis of dienes via SN20 reaction.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.12.122

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R. Ballini et al. / Tetrahedron Letters 51 (2010) 1233–1235
Table 1
NO2
H
HCOONH4-Pd/C
Ph
Effect of a variety of catalysts for the preparation of 3a
N
COOMe
EtOH, rt, 4h under N2
Ph
O
NO2
H
58%
NO2 MeO2C
MeOOC
MeO2C
MeOOC
Catalyst
CO2Me
3
+
3ka
Scheme 2. Synthesis of
4
Br
3
CO2Me
2a
1b
3ba
c
-lactame 4 from 3ka.
Catalyst
Mmol of
catalyst
Time (h)
Yield (%) of 3ba
Thus, our method represents a new, chemoselective way for the
SN20 reaction of nitroalkanes to dialkyl 2-(bromomethyl)fumarates
in which the nitro group can be completely preserved, allowing the
formation of a variety of polyfunctionalized adducts. Moreover, we
have demonstrated that our procedure can be conveniently applied
NaCO3- on polymer
support
CTAOH
0.5
Overnight 44
0.625
0.625
2.2
1.5
0.7
7
70
TBAF
KF/Al2O3
7
50
7
7
69
27
Traces
Traces
DBU
K2CO3
t-BuOK
1a
18
7
to the synthesis of an important class of compounds such as
c-
lactames.9
0.6
a
Large amount of nitrous acid elimination was observed.
Acknowledgments
Financial support from the University of Camerino and MIUR-
Italy (PRIN 2006, project: Sintesi Organiche Ecosostenibili Mediate
da Nuovi Sistemi Catalitici), and INCA-consortium are gratefully
acknowledged.
solution of 1b (1.2 mmol) and 2a (1 mmol), at 0 °C. After 5 min the
reaction was allowed to stir at room temperature for the appropri-
ate time (Table 2), and was extracted with EtOAc. The organic layer
was dried over Na2SO4, filtered, and concentrated under vacuum to
afford the crude product 3ba that was purified on flash chromatog-
raphy (cyclohexane–EtOAc).
Supplementary data
Then, a number of other different nitroalkanes 1 (including the
secondary nitroalkane, 1m) and dialkyl 2-(bromomethyl)fumarate
2 were chosen in order to assess the generality of our procedure. As
reported in Table 2, a large variety of adducts 3 were isolated as a
mixture of distereomers in good yields, even in the presence of
other functionalities.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.12.122.
References and notes
1. Ballini, R.; Bosica, G.; Fiorini, D.; Palmieri, A.; Petrini, M. Chem. Rev. 2005, 105,
933–971.
2. (a) Rosini, G.; Ballini, R. Synthesis 1988, 833–847; Rosini, G. In Comprehensive
Organic Synthesis; Trost, B. M., Ed.; Pergamon: New York, 1992; pp 321–340;
Ono, N. The Nitro Group in Organic Synthesis; Wiley VCH: New York, 2001; (d)
Ballini, R.; Palmieri, A. Curr. Org. Chem. 2006, 10, 2145–2169.
3. (a) Seebach, D.; Henning, R.; Lehr, F.; Widdowson, D. A. Tetrahedron Lett. 1977,
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Finally, in order to demonstrate the importance of the presence
of the nitro group we report, as representative example, the con-
version of the structure 3ka into the c-lactame 4 (58% overall yield,
Scheme 2) via HCOONH4–Pd/C reduction,8 by means of both the ni-
tro and the C,C double bond were reduced. Although three stereo-
genic centers are present, only two diastereomers of the compound
4 were isolated (1:1).
Table 2
Adducts 3 prepared
NO2
NO2
R1O2C
Br
R1O2C
CTAOH
rt
R
+
R
CO2R1
CO2R1
2a,b
1a-j
3
R
R1
Reaction time (h)
Yielda (%) of 3b (dr)
Me
n-Bu
1a
1b
Me
Me
2a
2a
5
7
3aa
3ba
75 (67:33)
70 (68:32)
O
(CH2)3
N
O
1c
Me
2a
12
3ca
68 (61:39)
n-C11H23
n-C7H15
CH2@CH(CH2)8
Me2(CH2)2
AcO(CH2)5
Ph
Ph(CH2)2
MeOCO(CH2)4
CH2@CH(CH2)8
Ph
1d
1e
1f
1g
1h
1j
1k
1l
1f
Me
Me
Me
Me
Me
Me
Me
Et
2a
2a
2a
2a
2a
2a
2a
2b
2b
2b
2a
7
7
7
7
6
7
6
12
12
7
3da
3ea
3fa
3ga
3ha
3ja
3ka
3lb
3fb
3jb
3ma
65 (84:16)
70 (54:46)
64 (63:37)
70 (53:47)
60 (51:49)
71 (71:29)
66 (60:40)
67 (72:28)
61 (60:40)
70 (53:47)
44
Et
Et
Me
1j
1m
–(CH2)5–
24
a
Yield of pure, isolated product.
b
The diastereomeric ratio was defined by 1H NMR studies.

R. Ballini et al. / Tetrahedron Letters 51 (2010) 1233–1235
1235
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