Potassium fluoride/basic alumina as far superior heterogeneous catalyst for the chemoselective conjugate addition of nitroalkanes to electron-poor alkenes having two electron-withdrawing groups in α- and β-positions

Article abstract of DOI:10.1002/adsc.200606105

The chemoselective, conjugate addition of nitroalkanes to electron-poor alkenes, with two electron-withdrawing groups in the α- and β-positions, can be easily performed at room temperature under solventless conditions using potassium fluoride/basic alumin

Full text of DOI:10.1002/adsc.200606105

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DOI: 10.1002/adsc.200606105
Potassium Fluoride/Basic Alumina as Far Superior Heterogeneous
Catalyst for the Chemoselective Conjugate Addition of Nitroal-
kanes to Electron-Poor Alkenes HavingTwo Electron-Withdraw-
ingGroups in a- and b-Positions
Roberto Ballinia,* and Alessandro Palmieria
a
Green Chemistry Group, Dipartimento di Scienze Chimiche, Università di Camerino, via S.Agostino 1, 62032 Camerino,
Italy
Fax : (+39)-073-740-2297; e-mail: roberto.ballini@unicam.it
Received: March 14, 2006; Accepted: May 19, 2006
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: The chemoselective, conjugate addition
of nitroalkanes to electron-poor alkenes, with two
electron-withdrawing groups in the a- and b-posi-
tions, can be easily performed at room temperature
under solventless conditions using potassium fluo-
ride/basic alumina as heterogeneous catalyst.
the b-position to the nitro function in the intermedi-
ate 3.
This discovery represents the key step for the one-
pot preparation of a large variety of unsaturated sys-
tems, from nitroalkanes.[4] However, in spite of the
great utility of the obtained unsaturated systems 4,
the elimination of the nitro group from the Michael
adduct 3 represents an important loss in terms of (i)
atomic economy and (ii) chances for further synthetic
applications, due to the easy conversion of the nitro
group into a variety of other powerful functionalities.
Thus, a new, chemoselective catalytic procedure for
the conjugate addition of 1 to 2, preserving the pres-
ence of the nitro group would be highly welcomed.
Solid catalysis is crucial to chemical technology, in
Keywords: conjugate addition; heterogeneous catal-
ysis; nitroalkanes; potassium fluoride/basic alumi-
na; solventless reaction
Nitroalkanes are a source of great utility for stabilized fact, product isolation is easier, the reactions often
carbanions since the high electron-withdrawing power run under milder conditions and it favours higher se-
of the nitro group provides an outstanding enhance- lectivity.In addition, the atom efficiency of the reac-
ment of the hydrogen acidity at the a-position.Nitro-
tion is improved, the process is simplified, the pre-
nate anions, generated from nitroalkanes under basic cious raw materials used in the manufacture of the
conditions, can be conveniently employed as carbon catalyst are given increased lifetime (through reuse),
nucleophiles for conjugate addition (Michael reac-
tion) to electron-poor alkenes.[1] Usually, these reac-
tions afford valuable nitro derivatives which can be
converted into an array of other molecules thanks to
the great versatility of the nitro group.[2] However, if
the nitro group is present in a suitable position on the
substrate, it could act as a leaving group with subse-
quent elimination of nitrous acid from the Michael
adduct.In fact, we have reported that the reaction of
nitroalkanes 1 with electron-poor alkenes bearing two
electron-withdrawing groups in the a- and b-positions,
2, under DBU catalysis, proceeds via a tandem Mi-
chael addition-elimination process affording the unsa-
turated molecules 4 with enhanced E stereoselectivity
(Scheme 1).[3] The nitrous acid elimination is induced
by the presence of the electron-withdrawing group at Scheme 1.
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Adv. Synth. Catal. 2006, 348, 1154 – 1156

Conjugate Addition of Nitroalkanes to Electron-Poor Alkenes
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the volume of waste is significantly reduced, and the nitro adduct from primary nitroalkanes (1a–c);
product isolation is often made easier.[5]
nevertheless, this seems not to be a problem since the
In this context, aliphatic nitro compounds have most widely used transformation of the nitro group is
demonstrated a great reactivity under solid catalysis, the Nef reaction (nitro to carbonyl)[2d] in which one
mainly in the formation of new carbon-carbon single stereogenic center is lost.
bonds.[6] Thus, we investigated the possibility to per-
Moreover, KF/basic Al2O3 catalysis offers one
form the chemoselective conjugate addition of nitro- more chance since, through the appropriate selection
alkanes to alkenes of type 2, with the aim of avoiding of the temperature, the direct formation of the a,b-
any elimination of the nitro group from the Michael unsaturated esters 4 can be also performed from the
adducts 3, under mild basic conditions with the help starting materials.
of solid catalysts.Our idea was first tested (Scheme 2)
In fact, if the reaction of 1 with 2 on KF/basic
in the reaction of methyl 4-nitrobutanoate (1a) with Al2O3 was carried out under solventless conditions
dimethyl maleate (2a), under solventless conditions and at 558C, the product 4 is directly obtained, in
and at room temperature, simple by mixing the sub- profitable yields (67–81%), from primary nitroal-
strates on a bed of a variety of solid, basic catalysts. kanes by the in situ conjugate addition-nitrous acid
As detailed in Table 1, it is evident that the best re-
sults were obtained under adsorbed KF catalysis,[7] in
Table 1. Tested solid catalysts.
particular using KF/basic alumina.[7c]
Catalyst
Yield [%][a]
of 3aa
In order to verify the generality of our procedure,
we examined our method with several substrates, in-
cluding primary and secondary nitroalkanes, and we
obtained good yields (70–92%, Table 2) of the ad-
ducts 3 in which the nitro functionality is preserved.
This procedure furnishes a diastereomeric mixture of
KF/basic alumina
KF/neutral alumina
Basic alumina
Hydrotalcite MG 70
Hydrotalcite MG 30
Amberlyst A-21
80
71
4
7
6
25
21
36
Amberlyst A-27
Silica supported-1,5,7-triazabicyclo-
[4.4.0]dec-5-ene (TBD)
N,N-Diethylpropylamine supported on
19
amorphous silica (KG-60-NEt2)
[a]
Scheme 2.
The reaction was stopped after 7 h.
Table 2. Results obtained by the conjugate addition of 1 to 2 under KF/basic alumina.
1
R
R1
2
Yield of 3 [%, h][a,b]
Yield of 4 [%, h][a,c]
a
a
b
b
c
MeOOC
MeOOC
CH3CH2
CH3CH2
C
H
H
H
H
H
H
a
b
a
b
a
b
a
b
a
b
aa (80, 7)
ab (78, 5)
ba (71, 6)
bb (76, 6)
ca (73, 6)
cb (84, 6)
da (92, 6)
db (70, 3)
ea (75, 6)
eb (70, 6)
aa (78, 7)
ab (67, 6)
ba (79, 6)
bb (72, 6)
ca (81, 16)
cb (71, 12)
da (traces)
db (traces)
ea (traces)
eb (traces)
Ph
A
c
Ph(CH2)2
ACHTREUNG
d
d
e
e
-(CH2)5-
-(CH2)5-
CH3
CH3
CH3
CH3
[a]
Yield of pure, isolated product.
[b] The reaction has been performed at room temperature.
[c]
The reaction has been performed at 558C.
Adv. Synth. Catal. 2006, 348, 1154 – 1156
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www.asc.wiley-vch.de
1155

Roberto Ballini and Alessandro Palmieri
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elimination, while secondary nitroalkanes convert Typical Procedure for the “One-Pot”
into the adduct 3, with traces of the elimination prod- Addition-Elimination of Nitroalkanes 1 to Alkenes 2;
uct 4.It is important to point out that the formation
of the unsaturated 1,4-dicarbonyl derivatives 4, from
primary nitroalkanes shows high E stereoselectivity
since the ratio E/Z is, for all the products,>95/5.
Thus, by the modular choice of the temperature,
the conjugate addition of nitroalkanes 1 to electron-
poor alkenes 2 having two electron-withdrawing
groups in the a- and b-positions, performed under
KF/basic Al2O3 catalysis, can be easily directed to the
(i) stereoselective (E) formation of a C/C double
bond (compounds 4), or (ii) chemoselective genera-
tion of a C/C single bond (compounds 3).
Preparation of 4
Following the same procedure as above, the reaction was
carried out at 558C.
Acknowledgements
Financial support from University of Camerino and MIUR is
gratefully acknowledged.
In conclusion, we have developed the first hetero-
geneous, solventless, chemoselective (or stereoselec-
tive) catalysis for the conjugate addition of both pri-
mary and secondary nitroalkanes to electron-poor al-
kenes possessing two electron-withdrawing groups in
the a- and b-positions.In addition, the very simple
and mild conditions make our procedure of great in-
terest from the practical point of view.At the present
time we are aiming to enlarge the potential of our
procedure and to verify its stereoselective outcome.
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ꢀ 2006 Wiley-VCH Verlag GmbH & Co.KGaA, Weinheim
Adv. Synth. Catal. 2006, 348, 1154 – 1156