Mukaiyama-Michael vinylogous additions to nitroalkenes under solvent-free conditions

Article abstract of DOI:10.2478/s11532-011-0122-7

The first Mukaiyama-Michael vinylogous reaction of a dioxinone-derived silyl ether to nitroalkenes is reported. The conjugate addition is performed in absence of any catalyst under solvent-free conditions, proceeding with satisfactory efficiency with variously substituted nitroalkenes. Moreover, the first organocatalyzed Mukaiyama-Michael vinylogous reaction of trimethylsilyloxyfuran to nitroalkenes is described.The reaction is promoted by Bronsted acids under solvent-free conditions, taking place in moderate to good yield with variously substituted nitroalkenes..

Full text of DOI:10.2478/s11532-011-0122-7

Cent. Eur. J. Chem. • 10(1) • 2012 • 47-53
DOI: 10.2478/s11532-011-0122-7
Central European Journal of Chemistry
Mukaiyama-Michael vinylogous additions
to nitroalkenes under solvent-free conditions
Invited Paper
Arrigo Scettri1, Rosaria Villano2, Patrizia Manzo1, Maria Rosaria Acocella1*
1Department of Chemistry and Biology, University of Salerno,
84084 Fisciano, (Salerno) Italy
2Institute of Biomolecular Chemistry-CNR,
Reg. Baldinca, 07040 Li Punti (Sassari), Italy
Received 22 June 2011; Accepted 17 September 2011
Abstract:
The first Mukaiyama-Michael vinylogous reaction of a dioxinone-derived silyl ether to nitroalkenes is reported. The conjugate addition
is performed in absence of any catalyst under solvent-free conditions, proceeding with satisfactory efficiency with variously substituted
nitroalkenes.
Moreover, the first organocatalyzed Mukaiyama-Michael vinylogous reaction of trimethylsilyloxyfuran to nitroalkenes is described.
The reaction is promoted by Brønsted acids under solvent-free conditions, taking place in moderate to good yield with variously
substituted nitroalkenes..
Keywords: Organocatalysis • Trimethylsilyloxyfuran • Dioxinone-derived silyl ether • Brønsted acids • Nitroalkenes
© Versita Sp. z o.o.
1. Introduction
received growing attention, so that many efficient
metal-free synthetic methods have been developed
for enantioselective addition of aldehydes [3c,10] and
ketones [10], malonate esters and ketoesters [11] to
nitroalkenes.
Michael addition is widely recognized as one of the most
important organic reactions for C-C bond construction [1]
and allows to obtain highly functionalized building blocks
for the total synthesis of organic compounds. Many
activating groups [2] can promote the formation of C-C
bond, but the strong electron-withdrawing character of
the nitro group makes nitroalkenes very good acceptors
for conjugate addition [3]. Moreover, the availability of a
consistent number of transformations, after the addition
has taken place, contributes to the always increasing
interest and development of its related chemistry.
In fact, as well known, the presence of nitro group in
an organic compound represents a powerful tool from
a preparative point of view for its easily manipulation
that permits the generation of different functionalities
[3b,4]. As reported in Fig. 1, the Nef reaction [5], the
nucleophilic displacement [6], the reduction to amino
group [7], the Meyer reaction [8], and the conversion into
a nitrile oxide [9], are only some examples of the possible
interconversions that nitro group can undergo.
The alternative approach, based on Lewis acid-
catalyzed addition of silyl enol ethers (known as
Mukaiyama-Michael reaction) has found broad
application in the case of α,β-unsaturated carbonyl
derivatives [12]. Conversely, nitroalkenes, in spite of their
enhanced reactivity as Michael acceptors, have only
been occasionally used in Mukaiyama-Michael reactions
[13], especially with regard to the vinylogous version.
Recent investigations have widely pointed out
the significant nucleophilic properties of the masked
acetoacetate ester 1 (Fig. 2), as confirmed by its
involvement in many procedures for vinylogous aldol
and imino-aldol reactions [14], taking place with very
high γ-selectivity both under metal- and organo-catalytic
conditions. It must be pointed out, that, in the case of silyl
dienolates of type 1, the control of regioselectivity is the
main difficulty to circumvent, since the presence of two
nucleophilic sites may result in the formation of α- and/or
γ-products (Fig. 1) [15].
Recently, the development of organocatalytic
asymmetric Michael additions to nitro olefins has
* E-mail: acord78@libero.it
47

Mukaiyama-Michael vinylogous additions
to nitroalkenes under solvent-free conditions
O
Nu
*
γ-selective vinylogous addition to appropriate acceptors,
we decided to focus our attention on the possible use
of the masked acetoacetate ester 1 and trimethyl-
silyloxyfuran 6 as Michael donors, in vinylogous
Mukaiyama- Michael addition to nitroalkenes 2
Nu
Nu
*
*
R'
R
R
R'
N
c
i
l
i
t
e
n
f
h
c
e
p
m
o
e
e
l
c
a
l
u
p
n
s
i
d
Nu
*
Nu
*
Michael
Red.
NH2
NO2
NO2
Nu
*
*
+
R
R
R
R'
R'
R'
2. Experimental procedure
H
R'=
Meyer
All the chemicals were purchased from Sigma-Aldrich
and used without any further purification. TLC was
performed on silica gel 60 F254 0.25 mm on glass plates
(Merck) and non-flash chromatography was performed
on silica gel (0.063-0.200 mm) (Merck). All 1H NMR and
13C NMR spectra were recorded with a DRX 400 MHz
Bruker instrument, by using CDCl3 (δ=7.26 ppm in
1H NMR spectra and δ=77.0 ppm in 13C NMR spectra)
Nu
*
R
COOH
Figure 1. Possible trasformations of nitro group.
O
O
1
as solvent (400.135 MHz for H and 100.03 MHz for
OSiMe3
13C). Data for 1H are reported as follows: chemical shift
(δ in ppm), multiplicity (s singlet, d doublet, t triplet,
dd doublet of doublets, m multiplet) and coupling costant
(J in Hz). Mass spectrometry analysis was carried out
using an electrospray spectrometer Waters 4 micro
quadrupole. The elemental analyses were performed
with FLASH EA 1112 Thermo equipment
γ-position α-position
E
+
E
+
1
O
O
O
O
E
O
O
2.1. General Procedure
E
The reaction was carried out in a dry vial. Nitroalkene 2
(149 mg, 1mmol) and silyloxydiene 1 (342 mg, 1.6 eq.)
were added and the resulting mixture stirred at room
temperature for the time indicated. After completion of
the reaction, the crude was purified by chromatography
on silica gel in gradient elution with n-Hexane/Ethyl
acetate to obtain the pure product.
2,2-dimethyl-6-(3-nitro-2-phenylpropyl)-4H-1,3-
dioxin-4-one 3a : Yellow oil. MS: m/z 292 [M+H+], 314
[M+Na+]; IR (KBr neat): 1725, 1635, 1554, 1378; 1H NMR
(400 MHz, CDCl3): 7.34-7.25 (m, 3 H), 7.18 (d, 2 H, J =
8.3 Hz), 5.13 (s, 1 H), 4.58 (d, 2 H, J = 7.5 Hz), 3.86-3.78
(m, 1 H), 2.74-2.61 (m, 2 H), 1.58 (s, 3 H), 1.40 (s, 3 H)
ppm. 13C NMR (100 MHz, CDCl3): 167.8 161.0, 137.5,
129.7, 129.0, 127.9, 107.4, 96.1, 80.4, 41.6, 37.3, 25.9,
24.9 ppm. Anal. Calcd for C15H17NO5: C, 61.85; H, 5.88;
Figure 2. Nucleophilic sites of silyl dienolate 1.
O
O
R
R
1
+
NO2
O
NO2
3
2
2
+
NO2
OSiMe3
O
O
O
R
5
4
Scheme 1. Vinylogous Mukaiyama-Michael addition of 1 and 6
to nitroalkenes.
Rather surprisingly,
1
has been rarely used N, 4.81. Found C, 61.73; H, 5.75; N, 4.69.
additions. 6-(2-(4-chlorophenyl)-3-nitropropyl)-2,2-
in
vinylogous Mukaiyama-Michael
The few available reports concern the addition of 1 to dimethyl-4H-1,3-dioxin-4-one 3b : Yellow oil. MS: m/z
particularly activated Michael acceptors, such as 2-acyl- 348 [M+Na+]; IR (KBr neat): 1726, 1635, 1554, 1378;
naphthoquinones,16 and at present no procedure for 1H NMR (400 MHz, CDCl3): 7.31 (d, 2 H, J = 8.3 Hz),
the addition to nitroalkenes, neither metal nor organo- 7.13 (d, 2H, J = 8.3 Hz), 5.14 (s, 1 H), 4.61-4.51 (m, 2
catalytic, is described.
Consequently, in order to evidence how synthetic 2.60 (dd, 1 H, J = 14.6, 9.5 Hz), 1.60 (s, 3 H), 1.46 (s,
equivalent of the γ−anion
can give a complete 3 H) ppm. 13C NMR (100 MHz, CDCl3): 167.4, 160.9,
H), 3.85-3.77 (m, 1 H) 2.70 (dd, 1 H, J = 14.6, 6.4 Hz),
48

A. Scettri et al.
136.1, 134.9, 129.7, 129.3, 107.5, 96.2, 90.1, 40.9, 37.2, 1378 cm-1 ; 1H NMR (400 MHz, CDCl3): 7.36 (d, 1 H, J =
25.8, 25.0 ppm. Anal. Calcd for C15H16ClNO5: C, 55.31; 1.88 Hz), 6.30 (dd, 1 H, J = 3.2, 1.88 Hz), 6.18 (d, 1 H,
H, 4.95; N, 4.30. Found C, 55.42; H, 4.83; N, 4.42.
J = 3.2 Hz), 5.19 (s, 1 H), 4.65 (dd, 1 H, J = 12.5, 7.5),
2,2-dimethyl-6-(3-nitro-2-p-tolylpropyl)-4H-1,3- 4.58 (dd, 1 H9, J = 12.5, 6.9); 4.01-3.94 ( m, 1 H), 2.72
dioxin-4-one 3c : Yellow oil. MS: m/z 306 [M+H+], (dd, 1 H, J = 14.5, 9.04 Hz), 2.65 (dd, 1 H, J = 14.5,
328 [M+Na+]; IR (KBr neat): 1726, 1636, 1555, 1378; 5.96 Hz), 1.66 (s, 3 H), 1.57 (s, 3 H) ppm. 13C NMR
1H NMR (400 MHz, CDCl3): 7.12 (d, 2 H, J = 8.0 Hz), (100 MHz, CDCl3): 167.3, 161.0, 150.7, 143.4, 110.5,
5.11 ( s, 1 H), 4.55 (d, 2 H, J = 7.6 Hz), 3.80-3.76 (m, 108.7, 96.1, 35.5, 30.8, 25.1, 23.4 ppm. Anal. Calcd for
1 H), 2.68 (dd, 1 H, J = 14.6, 6.0 Hz), 2.62 ( dd, 1 H, J = C13H15NO6: C, 55.51; H, 5.38; N, 4.98. Found C, 55.64;
14.6, 9.6 Hz), 2.30 (s, 3 H), 1.59 (s, 3 H), 1.44 (s, 3 H) H, 5.50; N, 5.10
ppm. 13C NMR (100 MHz, CDCl3): 167.9, 161.5, 138.7,
6-(2-cyclohexyl-3-nitropropyl)-2,2-dimethyl-4H-
134.4, 130.4, 127.8, 107.4, 96.0, 80.6, 41.2, 37.3, 25.9, 1,3-dioxin-4-one 3h :Yellow oil. MS: m/z [M+Na+];
24.9, 21.6 ppm. Anal. Calcd for C16H19NO5: C, 62.94; H, IR (KBr neat): 1730, 1636, 1553, 1377 cm-1; H NMR
1
6.27; N, 4.59. Found C, 62.82; H, 6.14; N, 4.46.
(400 MHz, CDCl3): 5.29 (s, 1 H), 4.44 (dd, 1 H, J = 12.5,
4-(3-(2,2-dimethyl-6-oxo-6H-1,3-dioxin-4-yl)-1- 6.2 Hz), 4.29 (dd, 1 H, J = 12.5, 7.0 Hz), 2.51-2.41 (m,
nitropropan-2-yl)benzonitrile 3d :Yellow oil. MS: m/z 3 H), 2.23 (dd, 1 H, J = 14.1, 7.3 Hz), 1.69 (s, 6 H),
317 [M+H+], 339 [M+Na+]; IR (KBr neat): 2230, 1725, 1.25-0.89 (m, 11 H) ppm. 13C NMR (100 MHz, CDCl3):
1555, 1378 cm-1; 1H NMR (400 MHz, CDCl3): 7.67 (d, 1 169.2, 161.1, 125.3, 107.3, 95.7, 40.5, 39.5, 33.9, 30.2,
H, J = 8.5 Hz), 7.34 (d, 1 H, J = 8.5 Hz), 5.17 (s, 1 H), 30.0, 29.7, 26.7, 26.4, 25.6, 25.5 ppm. Anal. Calcd for
4.67-4.57 (m, 2 H), 3.95-3.88 (m, 1 H), 2.75 (dd, 1 H, C15H13NO5: C, 60.59; H, 7.80; N, 4.71. Found C, 60.47;
J = 14.7, 6.4 Hz), 2.65 (dd, 1 H, J = 14.7, 9.1 Hz), 1.62 H, 7.69; N, 4.83.
(s, 3 H), 1.49 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
166.7, 160.7, 143.0, 133.5, 128.9, 118.5, 113.2, 107.6, data of compounds 5a-d and 5f-l see [30].
For general procedure, analytical and spectroscopic
96.4, 79.5, 41.4, 37.1, 25.7, 25.2 ppm. Anal. Calcd for
5-(1-nitroundecan-2-yl)furan-2(5H)-one 5e : 284
C16H16N2O5: C, 60.75; H, 5.10; N, 8.86. Found C, 60.61; (M+H+), 306 (M+Na+). IR (KBr, neat)1755, 1641, 1554,
H, 5.22;N, 8.72.
1382 cm-1. 1H NMR (400 MHz, CDCl3): 7.51-7.41 (m,
6-(2-(4-methoxyphenyl)-3-nitropropyl)-2,2- 1 Hanti + 1Hsyn), 6.26, (dd, 1 Hsyn, J = 5.7, 2.1), 6.18 (dd,
dimethyl-4H-1,3-dioxin-4-one 3e : Yellow oil. MS: m/z 1 Hanti, J = 5.7, 2.1), 5.20-5.16 (m, 1 Hanti + 1Hsyn), 4.52
344 [M+Na+]; IR (KBr neat): 1723, 1634, 1555, 1378, ((dd, 1Hanti, J = 13.4, 7.9), 4.39 (dd, 1 Hsyn, J = 13.4,
1
1016; H NMR (400 MHz, CDCl3): 7.09 8d, 1 H, J = 5.4), 4.35-4.30 (m, 1 Hanti + 1Hsyn), 2.65-2-40 (m, 1 Hanti
+
8.1 Hz), 6.85 (d, 1 H, J = 8.1 Hz), 5.12 (s, 1 H), 4.55-4.53 1Hsyn), 1.65-1.29 (m, 16 H), 0.85-0.90 (m, 3H). 13C NMR,
(m, 1 H), 3.80-3.73 (m, 4 H), 2.68 (dd, 1 H, J = 14.6, (100 MHz, CDCl3): 172.9, 154.4, 154.0, 124.0, 123.6,
5.9 Hz), 2.60 (dd, 1 H, J = 14.6, 9.7 Hz), 1.59 (s, 3 H), 83.0, 76.1, 74.7,40.5, 40.6, 40.3, 32.0, 29.7, 29.4, 27.5,
1.44 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): 168.0, 27.1, 26.8, 26.5, 25.9, 23.1,14.8 ppm. Anal. Calcd for
161.0, 130.0, 128.9, 115.1, 107.0, 96.1, 80.7, 55.8, 40.9, C15H25NO4,C, 63.58; H, 8.89; N, 4.94; Found C, 63.48;
37.4, 30.2, 25.9, 25.0 ppm. Anal. Calcd for C16H19NO6: H, 8.95 N, 4.87
C, 59.81; H, 5.96; N, 4.36. Found C, 59.78; H, 5.83; N,
4.25.
2,2-dimethyl-6-(3-nitro-2-(thiophen-2-yl)propyl)-
3. Results and discussion
4H-1,3-dioxin-4-one 3f : Yellow-orange oil. MS: m/z
344 [M+Na+]; IR (KBr neat): 1725, 1636, 1555, 1378;
Preliminarly, β-nitrostyrene 2a (R=Ph) was chosen as
the representative substrate, and, as is in our habit,
1H NMR (400 MHz, CDCl3): 7.25 (d, 1 H, J = 5.0 Hz),
6.94 (dd, 1 H, J = 5.04, 3.5 Hz), 6.90 (d, 1 H, J =
3.5 Hz), 5.20 (s, 1 H), 4.59 (d, 2 H, J = 7.2 Hz), 4.21-
4.12 (m, 1 H), 2.76 (dd, 1 H, J = 14.7, 5.7 Hz), 2.67
(dd, 1 H, J = 14.7, 9.5 Hz), 1.64 (s, 3 H), 1.51 (s, 3H)
ppm. 13C NMR (100 MHz, CDCl3): 167.3, 140.3, 129.7,
126.6, 125.9, 116.4, 107.5, 96.4, 80.6, 38.4, 30.1, 25.9,
24.9 ppm. Anal. Calcd for C13H15NO5S: C, 52.51; H,
5.09; N, 4.71. Found C, 52.39; H, 5.21;N, 4.83.
a control experiment was carried out in absence of any
catalyst under solvent-free conditions. The combination
of the nucleophilic/electrophilic properties of the
reagents 1 and 2a proved to be particularly successful
since the formation of the Michael γ-vinylogous adduct
3a occurred in good yield, complete selectivity and
rather reduced reaction time (Table 1, entry 1).
Furthermore, we were delighted to observe
a rather satisfactory level of general validity, since the
conjugate addition was found to take place under the
same conditions as in entry 1 (Table 1) with complete
6-(2-(furan-2-yl)-3-nitropropyl)-2,2-dimethyl-4H-
1,3-dioxin-4-one 3g :Yellow orange oil. MS: m/z 282
[M+H+], 304 [M+Na+]; IR (KBr neat): 1726, 1637, 1556,
49

Mukaiyama-Michael vinylogous additions
to nitroalkenes under solvent-free conditions
Table 1. Vinylogus Mukaiyama-Michael addition of 1 to nitroalkenes
2.
Entry
R
2
Time
(h)
Product
Yield
(%)a
1
2
3
4
5
6
7
8
Ph
2a
2b
2c
2d
2e
2f
1.40
3.00
3a
3b
3c
3d
3e
3f
82
67
64
69
77
61
54
40
4-ClC6H4
4-MeC6H4
4-CNC6H4
4-MeOC6H4
2-thienyl
2-furyl
Figure 3. Common starting materials for the synthesis of various
functionalized 2-(5H)-furanone derivatives.
24.00
24.00
24.00
5.00
O
OH
OH
O
O
P
PhO
PhO
O
2g
2h
3.30
3g
3h
OH
P
c-C6H11
23.00
OH
a All the yield refer to isolated, chromatographically pure compounds whose
structures were assigned by analytical and spectroscopic data.
9
10
Rac-8
Table 2. Conjugate addition of 6 to nitrostyrene 2a (R=Ph) catalysed
by Bronsted Acids.
Entry Catalyst
(mol%)
Time Temp Yield
Syn/antib
O
O
O
(h)
(°C)
(%)a
P
OH
1
-
1.5
1.5
r.t.
r.t.
12
20
40
25
60
60
56
75
70
82
27
57/43
57/43
58/42
58/42
66/34
75/25
65/35
75/25
60/40
75/25
70/30
2
PhCOOH(5)
PhCOOH (10)
Rac-8 (10)
9 (10)
3
48.0
24.0
22.0
20.0
17.0
18.0
0.5
-20
r.t.
Rac-11
Figure 4. Phenol and BINOL-based phosphoric acids.
4
5
-20
-20
-20
-20
r.t.
6
9 (20)
7
10 (10)
8
10 (20)
9
Rac-11 (10)
Rac-11 (5)
Rac-11 (10)
10
11c
6.0
-20
r.t.
24.0
Scheme 2. Conjugate addition of 6 to nitroalkenes 2.
a
All the yield refer to isolated, chromatographically pure compounds
whose structures were assigned by analytical and spectroscopic data.
b Diastereoisomeric ratios were determined by 1H NMR analysis (400 MHz)
on the crude products.
[18]. In fact, their reactivity, as synthetic equivalents
of the γ-anion of 2-(5H)-furanone 7, has been widely
exploited for the direct introduction of a γ-butenolide
core, which represents the main structural feature of a
thickly populated class of bioactive compounds.
However, while many important preparative
processes, such as alkylation [19], alkenylation [20],
arylation [21], aldol and imino-aldol reactions [22,23],
have benefited from the use of compounds of type 6,
rather modest attention was devoted to the conjugate
addition of 6 to electron deficient alkenes.
In fact, most of the reported procedures are based
on the use of α,β-unsaturated carbonyl compounds as
Michael acceptor, and they involve carbonyl activation
by Lewis Acids [24] or enolate activation by F- sources
[25]. Very interestingly, an organocatalytic approach
has recently proven to be successful in the asymmetric
addition of 6 to α,β-unsaturated aldehydes through
iminium ion activation [26].
However, although nitroalkenes are considered
among the best Michael acceptor, at present no
procedure is available for the conjugate addition of
2-silyloxyfuran of type 6 to give the adducts 5.
cThe reaction was performed in CH2Cl2 solution.
γ-selectivity and moderate to good yields in the case
of α,β-unsaturated nitro-compounds bearing aromatic
groups, irrespective of the electronic properties of the
substituents on the aromatic nucleus (entries 2-5).
Slightly lower efficiency was observed for substrates
2f-h bearing a heteroaromatic (entries 6 and 7 ) and,
most of all, an aliphatic substituent (entry 8).
It has to be noted that this new protocol, allowing
an easy access to polyfunctional adducts of type 3
under simple and cheap conditions, can be considered
of relevant synthetic value because of the broad
possibility of elaboration both of the –NO2 group and
dioxinone moiety. In a recent report, for example, the
vinylogous addition of an acylsilane-derived dienol ether
to nitroalkenes under Lewis acid catalysis represented
the key-step for an easy approach to 3-substituted
azepanes [17].
In the past two decades 2-trialkylsilyloxy furans
of type 6 (Fig. 2) have shown to be valuable starting
materials for the synthesis of a lot of variously substituted
and/or functionalized 2-(5H)-furanone derivatives
50

A. Scettri et al.
Table 3. Conjugate addition of 6 to nitroalkene 2 catalyzed by
Phosphoric acid 11.
phenol and BINOL-based organocatalysts 8-11 (Fig. 4)
under a variety of experimental conditions reported in
[30].
In entries 5-10 (Table 2) we were pleased to
observe a significant improvement of efficiency and
diastereoselectivity. Solvent free conditions, catalyst
loading and low temperature (-20°C), proved to be
determining factors for the achievement of a successful
process. Notably, the best results in terms of efficiency
and diastereoselectivity were obtained in presence of
catalyst Rac-11 (5 mol%, entry 10, Table 1).
It has to be noted that a dramatic drop of efficiency
was detected by performing the reaction in CH2Cl2
solution, obtaining the Michael adduct in rather poor
yield after prolonged reaction times (entry 9 vs 11,
Table 2). In order to verify the scope of the procedure,
a variety of nitroalkenes were examined reacting
with 2-trimethylsilyloxyfuran 6 under the optimized
conditions.
Entry
R
Time (h)
5
Yield (%)a Syn/antib
1
Ph
6
5a
5b
5c
5d
5e
5f
82
44
60
61
59
50
45
84
57
67
40
27
75/25
77/23
82/18
71/29
72/28
80/20
75/25
67/33
77/23
80/20
76/24
67/33
2
4-MeC6H4
c-C6H11
20
23
23
23
23
23
23
23
23
23
23
3
4
n-C7H15
5
n-C9H19
6
4-ClC6H4
2-thienyl
PhCH2CH2
4-CNC6H4
4-FC6H4
7
5g
5h
5i
8
9
10
11
12
5j
2-naphthyl
4-MeOC6H4
5k
5l
a All the yield refer to isolated, chromatographically pure compounds
whose structures were assigned by analytical and spectroscopic data.
b Diastereoisomeric ratios were determined by 1H NMR analysis (400 MHz)
on the crude products.
As reported in Table 3, the conjugate addition took
place in moderate to good yields with nitroalkenes
bearing in β-position aromatic (entries 1,2,6,9-12),
heteroaromatic (entry 7), aliphatic (entries 3,4,5,8)
substituents.
In recent reports the products of type 5 were
obtained in good yield and high stereoselectivity through
the direct use of furanone derivatives, as nucleophiles,
in presence of a chiral dinuclear zinc complex [27a] or 4. Conclusions
an axially chiral guanidine base [27b].
Therefore, we decided to focus our investigation on In conclusion, the first vinylogous Mukaiyama-
the achievement of an organocatalytic procedure for Michael addition of silyloxydiene 1 to nitroalkenes was
the conjugate addition of 4 to nitroalkenes as reported described, representing a rapid and easy approach
in Scheme 2. As usual, a preliminary experiment to the attainment of useful intermediates of relevant
was performed on β--nitrostyrene 2a, chosen again synthetic value for the possibility of further elaboration
as the representative substrate, in the absence of both of the –NO2 group and the dioxinone moiety. The
any catalyst under solvent-free conditions (entry 1, absence of catalyst and the solvent free conditions make
Table 2). The attainment of adduct 5a (R = Ph) in 12% this procedure economically convenient, operationally
yield after 1.5 hours pointed out the occurrence of a simple and environmental friendly.
competing background reaction proceeding in rather
Moreover, the catalytic properties of phenyl and
poor diastereoselectivity (syn/anti ratio = 57/43) and binaphthyl phosphoric acids have been conveniently
confirmed the notable properties of nitroalkenes as exploited for the achievement of the first organocatalytic
Michael acceptors.
procedure for the Mukaiyama-Michael addition
In an attempt to improve the efficiency and of silyloxyfuran to nitroalkenes, allowing an easy and
stereoselectivity of the reaction, the catalytic properties direct access to variously substituted γ-butenolides.
of some easily accessible H-donors, capable of lowering
the LUMO of nitroalkenes through hydrogen bonding, required and, after the completion of the reaction, the
were examined [28]. crude mixtures can be directly submitted to purification
In both protocols no solvent and no work-up are
The use of benzoic acid and racemic BINOL, as by column chromatography.
H-donors, proved to be unsatisfactory both in terms of
efficiency and diastereoselectivity (entries 2-4, Table 2).
Acknowledgements
Because of the ever increasing importance of organic
phosphoric acids in organic synthesis [29], we decided to
explore the catalytic properties of some easily available
We are grateful to MIUR and University of Salerno for
financial support.
51

Mukaiyama-Michael vinylogous additions
to nitroalkenes under solvent-free conditions
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