Novel synthesis of α-nitroalkenes from nitroalkanes via halogenation of intermediate N,N-bis(silyloxy)enamines

Article abstract of DOI:10.1016/j.tetlet.2005.05.113

An approach to conjugated nitroalkenes via oxidation of N,N-bis(silyloxy)enamines with bromine or iodine in the presence of tetra-n-butylammonium acetate is described. The acetate ion plays a key role by acting as a mild desilylating reagent. This new strategy allows the synthesis of α-nitroalkenes from the corresponding nitroalkanes.

Full text of DOI:10.1016/j.tetlet.2005.05.113

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 5203–5205
Novel synthesis of a-nitroalkenes from nitroalkanes
via halogenation of intermediate N,N-bis(silyloxy)enamines
Roman A. Kunetsky, Alexander D. Dilman,* Marina I. Struchkova,
Vladimir A. Tartakovsky and Sema L. Ioffe
N. D. Zelinsky Institute of Organic Chemistry, 119991 Moscow, Leninsky prosp. 47, Russian Federation
Received 20 April 2005; revised 19 May 2005; accepted 25 May 2005
Available online 14 June 2005
Abstract—An approach to conjugated nitroalkenes via oxidation of N,N-bis(silyloxy)enamines with bromine or iodine in the
presence of tetra-n-butylammonium acetate is described. The acetate ion plays a key role by acting as a mild desilylating reagent.
This new strategy allows the synthesis of a-nitroalkenes from the corresponding nitroalkanes.
Ó 2005 Elsevier Ltd. All rights reserved.
Conjugated nitroalkenes have found widespread use in
organic synthesis as Michael acceptors,1 dienophiles,1a,2
and heterodienes.3 Therefore, the development of new
convenient procedures for their synthesis constitutes
an important goal.
NO2
NO2
R
R
N(OSiMe3)2
R
1
Scheme 1.
Several strategies for the synthesis of nitroalkenes are
known. The most straightforward methodology involves
condensation of nitroalkanes with carbonyl compounds
(Henry reaction4), proceeding through the intermediacy
of b-nitroalcohols. Other approaches utilize starting
materials with a ÔpreformedÕ carbon skeleton. Examples
include nitromercuration5 and nitroselenation6 of alk-
enes, with subsequent transformation of the Hg- and
Se-containing intermediates, and ipso-nitration of vinyl
stannanes.7
Herein, we present a mild and convenient protocol for
the synthesis of nitroalkenes using an oxidative strategy,
through bis-O-silyl derivatives of nitro compounds—
N,N-bis(silyloxy)enamines (BENAs). The intermediate
BENAs 1 can be easily obtained by double O-silylation
of nitro compounds and detailed procedures for this
step were reported previously.9 In this letter, the major
emphasis is placed on transformation of enamines 1 into
a-nitroalkenes.
Selective oxidation of the carbon skeleton of nitroalk-
anes would be a particularly attractive method for the
synthesis of nitroalkenes (Scheme 1). However, there is
only one publication along these lines, which described
elimination from intermediate a-seleno-substituted nitro
compounds.8 Obviously, the high cost of selenium
reagents and the moderate yields of products narrow
the applicability of this procedure.
The oxidation of BENAs was performed by reaction
with halogens (Br2 or I2) in the presence of tetra-n-butyl-
ammonium acetate (Scheme 2, Table 1). As reported
previously,10 BENAs can behave as mild nucleophilic
reagents with a reactivity comparable to that of silyl
enol ethers. It is thus quite likely that on interaction
of BENAs 1 with halogens the iminium cations 2 are
initially formed, which lose a trimethylsilyl group lead-
ing to the previously unknown b-halo silyl nitronates
3. The latter species readily eliminate a molecule of
halosilane (Me3SiX) affording nitroalkenes 4.11
Keywords: Nitroalkenes; N,N-bis(silyloxy)enamines; Halogenation;
Silyl nitronates.
*
The thermodynamically driven halosilane elimination
seems to be the key step of the present protocol.
Corresponding author. Tel.: +7 095 938 35 60; fax: +7 095 135 53
28; e-mail: adil25@mail.ru
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.05.113

5204
R. A. Kunetsky et al. / Tetrahedron Letters 46 (2005) 5203–5205
dichloromethane followed by warming to room
X2, 2 Bu4NOAc
NO2
R2
N(OSiMe3)2
temperature.16 To achieve good yields of internal nitro-
alkenes, the use of bromine is preferable (cf. entries
12 and 13).
R2
1a-h
R1
CH2Cl2, —78 to 0 °C
R1
4a-h
AcOSiMe3 + X
—XSiMe3
X
The isolation of the simplest nitroalkenes can be accom-
panied by losses of the material due to their volatility
and propensity to polymerization. Nevertheless, such
compounds can be used in further transformations with-
out isolation from the reaction mixtures, as exemplified
by trapping of nitroethylene with cyclopentadiene (entry
9). Nitroalkenes 4g,h with internal double bonds were
formed as E-isomers exclusively.
AcO
X
OSiMe3
X
O
N
N
R2
OSiMe3
R2
OSiMe3
R1
R1
2
3
AcO
AcOSiMe3
Scheme 2.
In conclusion, a new mild protocol for the synthesis of
conjugated nitroalkenes by selective oxidation of the
carbon skeleton of the corresponding nitro compounds
by means of halogenation of an intermediate BENA
is described. Taking into account that generation of
BENAs from secondary nitroalkanes is a highly regio-
selective process,9a this approach allows one to control
the position of the C@C-double bond in the target
nitroalkene.
Table 1. Synthesis of nitroalkenes 4
Entry R1
R2
Procedurea
4
Yield of
4 (%)b
1
(CH2)2CO2Me
H
H
H
H
A
B
A
B
A
B
A
B
A
A
A
A
B
4a 82
2
4a 92
4b 62
4b 82
4c 76
4c 78
4d 95c
4d 71c
4e 82d
4f 75e
4g 76
4h 90c
4h 23c
3
Bn
4
5
CH2OTBS
Me
6
7
8
Acknowledgments
9
H
H
10
11
12
13
Ph
H
H
This work was supported by the Russian Foundation
for Basic Research (project 05–03–32733).
n-C5H11
Me
H
a Procedure A: 1:Br2:n-Bu4NOAc = 1:1.1:2.2. Procedure B: 1:I2:n-
Bu4NOAc = 1:1:2.2.
b Isolated yield, unless otherwise stated.
Supplementary data
c Determined by NMR spectroscopy with an internal standard.
d Yield of the cycloadduct of 4e with cyclopentadiene.
e Compound 4f is highly prone to polymerization on concentration of
its solutions.
Supplementary data associated with this article can be
found, in the online version at doi:10.1016/j.tetlet.2005.
05.113.
References and notes
According to the literature data,12 as a rule, in equilibrium
mixtures of silyl nitronates, trans-isomers dominate,
which cannot undergo concerted halosilane elimination.
However, this process can take place from minor
concentrations of cis-isomers resulting from rapid 1,3-
O,O-migration of the silyl group.13
1. (a) Barrett, A. G. M.; Graboski, G. G. Chem. Rev. 1986,
86, 751–762; (b) Efremov, D. A.; Perekalin, V. V.; Lipina,
E. S.; Berestovitskaya, V. M. Nitroalkenes; John Wiley &
Sons: New York, 1994; (c) Ono, N. The Nitro Group in
Organic Synthesis; Wiley-VCH: New York, 2001, pp 70–
103.
2. Ono, N. The Nitro Group in Organic Synthesis; Wiley-
VCH: New York, 2001, pp 231–248.
3. (a) Denmark, S. E.; Thorarensen, A. Chem. Rev. 1996, 96,
137–165; (b) Seebach, D.; Lyapkalo, I. M.; Dahinden, R.
Helv. Chim. Acta 1999, 82, 1829–1842.
4. (a) Henry, L. C. R. Acad. Sci. 1895, 120, 1265; (b) Ono, N.
The Nitro Group in Organic Synthesis; Wiley-VCH: New
York, 2001, pp 38–44; (c) Luzzio, F. A. Tetrahedron 2001,
57, 915–945.
5. Corey, E. J.; Estreicher, H. J. Am. Chem. Soc. 1978, 100,
6294–6295.
6. Hayama, T.; Tomoda, S.; Takeuchi, Y.; Nomura, Y.
Tetrahedron Lett. 1982, 23, 4733–4734.
7. Corey, E. J.; Estreicher, H. Tetrahedron Lett. 1980, 21,
1113–1116.
8. Sakakibara, T.; Takai, I.; Ohara, E.; Sudoh, R. J. Chem.
Soc., Chem. Commun. 1981, 261–262.
It should be pointed out that the use of standard halo-
genating agents (Cl2, Br2, ICl, SO2Cl2, NCS, NBS) in
the absence of tetra-n-butylammonium acetate resulted
in complete conversion of starting BENA, but gave only
traces or low yields of target nitroalkenes 4. This may be
associated with a high reactivity of iminium ion 2, which
is capable of decomposition and rearrangement of the
starting BENA.14 Furthermore, the halosilanes Me3SiX
(X = Br or I) formed in the course of the reaction can
also consume BENA.9a We believe that acetate ions
serve to minimize these side processes by desilylating
the cation 2 and scavenging Me3SiX. Attempts to use
quaternary ammonium chloride and fluoride salts for
these purposes were unsuccessful.15
The optimal procedure for the synthesis of nitroalkenes
4a–h includes mixing of the reagents at À78 °C in
9. (a) Dilman, A. D.; Tishkov, A. A.; Lyapkalo, I. M.; Ioffe,
S. L.; Strelenko, Yu. A.; Tartakovsky, V. A. Synthesis

R. A. Kunetsky et al. / Tetrahedron Letters 46 (2005) 5203–5205
5205
1998, 181–185; (b) For the synthesis of BENA with a
functionalized double bond see: Dilman, A. D.; Tishkov,
A. A.; Lyapkalo, I. M.; Ioffe, S. L.; Kachala, V. V.;
Strelenko, Yu. A.; Tartakovsky, V. A. J. Chem. Soc.,
Perkin Trans. 1 2000, 2926–2929.
I. M.; Ioffe, S. L.; Strelenko, Yu. A.; Tartakovsky, V. A.
Synthesis 1999, 1767–1775.
16. (a) Bromination of BENAs (general procedure A, Table
1). A solution of Br2 (57 lL, 1.1 mmol) in CH2Cl2 (1 mL)
was added to
a solution of n-Bu4NOAc (665 mg,
10. Dilman, A. D.; Ioffe, S. L.; Mayr, H. J. Org. Chem. 2001,
66, 3196–3200.
2.2 mmol) in CH2Cl2 (2.5 mL) at À78 °C. Then, a solution
of BENA 1 (1 mmol) in CH2Cl2 (1.5 mL) was slowly
added with vigorous stirring, the mixture was kept for
15 min at À78 °C, and the cooling bath was removed. The
mixture was allowed to warm to room temperature,
concentrated, the residue treated with ether (10 mL),
stirred for an additional 15 min and the precipitate was
filtered off. The filtrate was concentrated and the residue
was purified by chromatography on silica gel eluting with
hexane/ethyl acetate (see supplementary data for details).
(b) Iodination of BENAs (general procedure B, Table 1).
n-Bu4NOAc (665 mg, 2.2 mmol) and I2 (254 mg,
1.1 mmol) were dissolved in CH2Cl2 (3.5 mL). After
stirring for 15 min at room temperature, the mixture was
cooled to À78 °C and a solution of BENA (1 mmol) in
CH2Cl2 (1.5 mL) was added slowly with vigorous stirring.
After 15 min at À78 °C, the cooling bath was removed, the
mixture was allowed to warm to room temperature and
worked up as described in the previous procedure (see
supplementary data for details).
11. Formation and fast fragmentation of a b-chlorosilyl
nitronate has been proposed, though its trapping in a
1,3-dipolar cycloaddition reaction failed, see: Ioffe, S. L.;
Makarenkova, L. M.; Strelenko, Yu. A.; Tartakovsky, V.
A. Zh. Org. Khim. 1995, 31, 1208–1212.
12. (a) Shitkin, V. M.; Ioffe, S. L.; Kashutina, M. V.;
Tartakovskii, V. A. Izv. Acad. Nauk SSSR, Ser. Khim.
1977, 2266–2273; (b) Marti, R. E.; Heinzer, J.; Seebach, D.
Liebigs Ann. 1995, 1193–1215.
13. Ioffe, S. L.; Shashkov, A. S.; Blumenfeld, A. L.; Litvak, K.
M. Izv. Acad. Nauk SSSR, Ser. Khim. 1977, 2836–2838.
14. Decomposition and rearrangement of BENAs into a-
silyloxyoximes was discussed within the context of the
interaction of BENAs with carbocations, see: Dilman, A.
D.; Lyapkalo, I. M.; Ioffe, S. L.; Strelenko, Yu. A.;
Tartakovsky, V. A. J. Org. Chem. 2000, 65, 8826–8829.
15. It is known that BENAs rapidly decompose in the
presence of fluoride ions, see: Dilman, A. D.; Lyapkalo,