Domino reactions for the synthesis of various α-substituted nitro alkenes

Article abstract of DOI:10.1039/c1ob06260c

Efficient one-pot methods for the synthesis of variously functionalised conjugated nitro alkenes have been reported. Despite the utility in different fields of these compounds, only a few multi-step syntheses have been reported in the literature, giving t

Full text of DOI:10.1039/c1ob06260c

Organic &
Biomolecular
Chemistry
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Volume 10 | Number 3 | 21 January 2012 | Pages 465–684
ISSN 1477-0520
PAPER
Stefania Fioravanti, Lucio Pellacani and Maria Cecilia Vergari
Domino reactions for the synthesis of various α-substituted nitro alkenes
1477-0520(2012)10:3;1-K

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PAPER
Domino reactions for the synthesis of various a-substituted nitro alkenes†
Stefania Fioravanti,* Lucio Pellacani* and Maria Cecilia Vergari
Received 26th July 2011, Accepted 12th September 2011
DOI: 10.1039/c1ob06260c
Efficient one-pot methods for the synthesis of variously functionalised conjugated nitro alkenes have
been reported. Despite the utility in different fields of these compounds, only a few multi-step syntheses
have been reported in the literature, giving the target compounds in low overall yields. a-Nitro acrylates
or cinnamates, a-nitro a,b-unsaturated ketones and, most importantly, aromatic and heteroaromatic
(E)- 2-nitro allylic alcohols, compounds characterised by a well-known anticancer activity, were
obtained in high yields and high diastereomeric purity by a domino condensation-dehydration process.
logical activity. In fact, Panda et coll. found that these kind of
compounds present anticancer activity towards HeLa cells, when
Introduction
an aromatic group directly bound to the C C is present.10
Aromatic and heteroaromatic (E)-2-nitro allylic alcohols were
synthesized by a three-step procedure tested under different
reaction conditions and involving in sequence a Henry conden-
sation, a nitroaldol dehydration, and finally a Morita-Baylis-
Hillman reaction (MBHR)11 performed in the presence of aqueous
formaldehyde (Scheme 1).12
The synthesis of conjugated nitro alkenes has been a challenge
for many years because of their importance in terms either
of their application as biological and pharmacologically active
substances or of their synthetic utility in organic chemistry as key
intermediates in the construction of more complex molecules.1
The synthetic versatility of these derivatives arises from the
powerful electron-withdrawing effect of the nitro substituent
that make them hard electrophiles and, therefore, good Michael
acceptors2 as well as efficient dienophiles in Diels-Alder reactions;3
moreover, the nitro group can be converted into many other
functionalities by simple transformations.4
Despite the utility in different fields of these compounds, to
the best of our knowledge, just few syntheses were reported in
the literature by a multi-step synthesis,1a,5 resulting in low overall
yields of the desired compounds. As is well known, the most
common preparation of nitro alkenes involves a two-step reaction
that strongly decreases the overall yield of their synthesis. In fact,
a Henry reaction6 leading to a C–C bond formation between a
carbonyl compound and a nitro alkane,7 followed by a dehydration
step, often performed under harsh conditions, was required to
obtain the target compounds.
Scheme 1 Aryl 2-nitro allylic alcohols by multi-step procedures.
The compounds were obtained in moderate to good yields, but
it is necessary to stress that the reported data are referred only to
the MBHR final step.
Results and discussion
Continuing our studies on the synthesis of functionalised con-
jugated nitro alkenes, the possibility of obtaining very inter-
esting aromatic or heteroaromatic nitro allylic alcohols starting
from 2-nitroethanol and different suitable aldehydes, by a high-
throughput one-pot methodology, was considered.
˚
Recently, we reported the use of activated 4 A molecular
sieves and piperidine as catalyst as a simple and efficient one-
pot method to obtain unfunctionalised conjugated nitro alkenes
in good yields.8 Furthermore, nitro allylic O-nosyl hydroxylamines
were successfully achieved starting from 2-nitro allylic alco-
hols, compounds easily obtained by our fast one-pot synthetic
methodology.9
˚
Thus, 2-nitroethanol was reacted over 4 A molecular sieves, in
the presence of a catalytic amount of piperidine, with aromatic or
heteroaromatic aldehydes 1a–g under an inert atmosphere (Ar) at
reflux of anhydrous toluene (Method A). The results are reported
in Table 1.
Concerning the 2-nitro allylic alcohols (hydroxymethyl nitro
alkenes) recent studies have demonstrated their significant bio-
As reported in Table 1, the domino reactions proceed with high
stereoselectivity, giving only the (E)-2-nitro allylic alcohols 2a–g
with high purity and in very good overall yields, as confirmed by
NMR analyses. We want to stress that when we performed the
Dipartimento di Chimica, Universita` degli Studi di Roma “La Sapienza”,
P.le Aldo Moro 5, I-00185, Roma, Italy. E-mail: lucio.pellacani@
uniroma1.it, stefania.fioravanti@uniroma1.it; Fax: +39 06490631; Tel: +39
0649913673; +39 0649913098
˚
† Electronic supplementary information (ESI) available: 1H and 13C NMR
spectra for all the new compounds. See DOI: 10.1039/c1ob06260c
reaction without 4 A molecular sieves, not under inert atmosphere
and at room temperature, the expected products were obtained in
524 | Org. Biomol. Chem., 2012, 10, 524–528
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Table 1 Stereoselective one-pot synthesis of (E)-2-nitro allylic alcohols
Table 2 One-pot synthesis of a-nitro acrylates and cinnamates
Entry
1
1
a
Ar
2
a
Yield (%)a
70
Entry
1
1
a
Ar
Method
3
a
E/Z ratioa
Yield (%)b
A
B
50:50
50:50
50
83
2
3
b
c
b
c
65
60
2
3
4
b
c
d
A
B
B
b
c
d
50:50
40:60
35:65
76
84d
95e
4
5
d
e
d
e
65
50
5
6
7
8
f
A
A
A
f
40:60
40:60
30:70
95
83
97
g
h
i
g
h
i
6
7
f
f
95
85
g
g
A
B
40:60
40:60
51
91
a After filtration of the crude mixture on celite.
e
9
j
B
B
j
30:70
30:70
95d
low yields, with the Henry adduct intermediates in the 1H NMR
spectra of the crude mixtures being distinctly present. Therefore,
10
k
k
86c
˚
the higher temperature, the inert atmosphere and the use of 4 A
molecular sieves are conditions absolutely required to obtain total
conversion and complete intermediate dehydration.
a By 1H NMR analysis on the crude mixture. b After purification on silica
gel. c After 48 h. d After 24 h. e After 4 h.
Buoyed by these results, the synthetic methodology has been
applied to other different functionalised a-nitro alkenes for the
synthesis of them are often required complex and few efficient
procedures, involving even toxic and expensive reagents.13
Thus, ethyl nitroacetate was considered as the ideal methylene
compound for obtaining interesting a-nitro cinnamates and
acrylates, known as versatile building blocks in organic synthesis
and widely used due to their reactivity as good Michael acceptors
and to the possibility of transforming either the nitro or the ester
group into many other functional groups.13b,14
The reactions were performed by following Method A, but
starting from several aryl or alkyl aldehydes the procedure failed
and the synthesis starting from these last compounds required
some changes, using Et3N instead of piperidine as base, ZrCl4 as
catalyst and THF as solvent (Method B). The results are reported
in Table 2.
As shown in Table 2, the expected a-nitro cinnamates 3a–i
and acrylates 3j,k were obtained in all cases as E/Z mixtures
in good to excellent yields, the stereoselectivity of the reaction
decreasing as a function of the starting aldehydes. The Z isomer
is almost always the major one. Surprisingly, following Method
A, the one-pot condensation reactions do not take place starting
from aldehydes 1c,d (entries 3, 4) and 1j,k (entries 9, 10). In
effect, only when starting from 1d and performing the reaction
under Method A, the corresponding a-nitro cinnamate 3d was
observed but only in very low yields (< 5%). Then, the reactions
on these substrates were attempted replacing piperidine with Et3N
or using basic alumina as both base and dehydrating agent,15 but
also under these conditions the expected compounds were not
observed.
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Table 3 Synthesis of (E/Z)-a-nitro a,b-unsaturated ketones
analogous but emphasised to that observed for the nitro alkenes
derived from ethyl nitroacetate (see Table 2). In fact, the stability
of the Z isomer probably arises from a weak intramolecular C–
H ◊ ◊ ◊ O hydrogen bond formation,22 which is favoured with the
acyl group with respect to the nitro group, as reported in the
literature.23
We want to stress that the higher diastereoselective induction
either for E or Z isomers is observed when an electronic effect
(entry 3) or a steric hindrance (entry 4), respectively, are present
on both reagents.
Entry Alkene
R
R¢
Time (h) E/Z ratioa Yield (%)b
1
2
3
4
5
6
6
i-Bu
Ph
16
60
72
85:15
80:20
95:5
10:90
20:80
40:60
85
70
65
93
60
85
7
sec-Bu
2-Furyl
i-Bu
Conclusions
8
9
10
11
i-Bu 20
In this paper we present new and efficient one-pot methods for the
synthesis of a-substituted nitro alkenes, important compounds
for their application in organic synthesis24 and for their biological
significance. In particular, we devised a one-pot synthesis of aryl
(E)-nitro allylic alcohols, characterised by a known anticancer
activity. Moreover, our methodology allows to obtain these
compounds in high yields and high diastereomeric purity. Despite
their potential use and application in many fields, only a few
examples of synthetic procedure to obtain these compounds have
been reported in the literature so far.
sec-Bu
2-Furyl
48
16
a By 1H NMR analysis on the crude mixture. b After purification on silica
gel.
Therefore, by changing a synthetic method reported in the
literature13a involving the use of very toxic TiCl4, Method B
was successfully developed, maintaining the presence of 4 A
˚
molecular sieves as dehydrating agents, using Et3N as base and,
most importantly, adding ZrCl4 as Lewis acid. ZrCl4 was chosen
as catalyst, instead of TiCl4, being easier to handle, stronger Lewis
acid, cheaper and more environmentally friendly.16
Under these different conditions, the reactions were kept at
reflux of anhydrous THF and led to the expected E/Z compounds
in excellent yields (Table 2, entries 1, 3, 4, 8, 9 and 10).
This unexpected reactive behaviour of aryl aldehydes 1c, d and
alkyl aldehydes 1j, k might be due to the strong ability of ZrCl4 to
stabilize the negative charge on the oxygen atom, thus maximising
the electrophilicity of the aldehyde carbon.
Continuing our studies on the possible one-pot strategies to
synthesise different functionalised nitro alkenes, we found, to the
best of our knowledge, that only one method to obtain a-nitro
a,b-unsaturated ketones was reported, involving an acid-catalysed
reaction between heteroaromatic aldehydes and nitro carbonyl
compounds in the presence of SOCl2 or acetic acid at reflux of
benzene.17
In light of the greater reactivity of nitro ketones as active
methylene compounds with respect to nitro esters, a direct base
Al2O3-catalysed synthesis of a-nitro a,b-unsaturated ketones was
attempted. By following reported procedures,18 compounds 1a, e,
f were reacted with the commercially available nitromethyl phenyl
ketone (4) and with the isobutyl nitromethyl ketone (5), the last
one synthesised starting from isovaleraldehyde and nitromethane,
by a procedure reported in the literature.19,20 The results of
the Al2O3-catalysed Knoevenagel condensations are reported in
Table 3.
Experimental section
General remarks
All reactions requiring dry conditions were performed in flame
dried glassware under inert atmosphere (Ar). All the commercial
available reagents [(aldehydes 1a–k, 2-nitroethanol, ethyl nitroac-
etate and nitromethyl phenyl ketone (4)] and the anhydrous
solvents were purchased from Aldrich and used without further
˚
purification. Molecular sieves type 4 A (beads, diameter 1.7–
2.4 mm, Aldrich) were activated by heating at 280 ◦C for 2 h
under vacuum. Basic Al2O3 (70–230 mesh ASTM) were purchased
from Fluka. The reactions were monitored by 1H NMR analysis.
Flash chromatography were performed on Merck silica gel (60,
particle size: 0.040–0.063 mm).1H NMR and 13C NMR spectra
were recorded on a VARIAN XL-300 spectrometer at room
temperature. CDCl3 was used as the solvent and CHCl3 as the
internal standard. FT-IR spectra were recorded on a Perkin–
Elmer 1600 spectrophotometer in CHCl3 as the solvent. HRMS
analyses were performed using a Micromass Q-TOF Micro
quadrupole-time of flight (TOF) mass spectrometer equipped
with an ESI source and a syringe pump. The experiments were
conducted in the positive ion mode. Isobutyl nitromethyl ketone
(5)25 was synthesised, according to the procedure reported in the
literature.19,20 2a,b, d–g,10 2c,26 3a,27 3c,28 3b,d,f,g,13a 3h,i,29 3j,30 and
817 are known compounds.
After filtration of Al2O3, (E/Z)-a-nitro a,b-unsaturated ke-
tones were obtained in very good yields and high purity, as detected
by NMR spectra. Starting from 4, the E isomer is always the major
one, while starting from 5 the stereoselective outcome was inverted,
giving the Z isomer as the major one (entries 4–6).
General procedure for the one-pot synthesis of (E)-nitro allylic
alcohols 2a–g (Method A)
A solution of 2-nitroethanol (228 mg, 2.5 mmol) and an aromatic
or heteroaromatic aldehyde 1a–g (2.5 mmol) in anhydrous PhCH3
(12 mL) was added under Ar in a round-bottom flask containing
The presence of an aryl group as substituent of the C
O
˚
increases the stability of the E isomer as a consequence of a
high coplanarity with the alkene p system.21 Noteworthy, the
nitro alkenes derived from alkyl ketones show a stereoselectivity
previously activated 4 A molecular sieves (5 g). A catalytic amount
of piperidine was added (10% mol) and the reactions, followed by
the H NMR analysis, were kept at reflux for 4 h. The crude
1
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mixtures were filtered under inert atmosphere (Ar or N2) through
a plug of celite to remove the molecular sieves using CH2Cl2
as eluent and the solvents were evaporated under vacuum. The
products were purified by flash chromatography on silica gel
(eluent: hexane/ethyl acetate = 8:2 for 2a,g; 7:3 for 2b,d,f; 25:75
for 2c; 85:15 for 2e.)
Al2O3 were added and the mixtures were kept stirring at room
temperature. The reactions were followed by H NMR analyses
(see Table 3). Then, the mixtures were filtered off and the solvent
was evaporated under vacuum to give the crude mixtures. The
products were purified by flash chromatography on silica gel (8
was purified using as eluent hexane/dichloromethane = 3:7).
1
(E/Z)-5-Methyl-2-nitro-1-phenylhex-2-en-1-one (E/Z-6). Iso-
lated yield 85%. Pale yellow oil. Purified by flash chromatography
on silica gel (eluent: hexane/ethyl acetate = 9:1). nmax cm-1 2954,
General procedure for the one-pot synthesis of a-nitro acrylates
and cinnamates 3a,b,f–i
1
1679, 1598, 1536. H NMR (CDCl3, 300 MHz): d 7.89–7.85 (m,
For the synthesis of title compounds the general procedure before
reported (Method A) was followed. The products were purified
by flash chromatography on silica gel (eluent: hexane/ethyl
acetate = 7:3 for 3a; 9:1 for 3b; 8:2 for 3g,h; 85:15 for 3i. 3f was
purified using hexane/dichloromethane = 4:6 as eluent).
2H, major isomer), 7.77–7.74 (m, 2H, minor isomer), 7.67–7.61
(m, 2H), 7.56–7.48 (m, 5H), 6.64 (t, J = 7.8 Hz, 1H, minor), 2.38
(dd, J = 6.9 Hz, 7.7 Hz, 2H, minor), 2.13 (dd, J = 6.8 Hz, 8.2 Hz,
2H major), 1.95–1.81 (m, 2H), 1.00 (d, J = 6.7 Hz, 6H, minor), 0.90
(d, J = 6.7 Hz, 6H, major). 13C NMR (CDCl3, 75 MHz): d 188.5
(2C), 141.4 (major isomer), 141.1 (minor isomer), 135.6 (minor),
135.5 (major), 134.6 (2C), 133.6 (2C), 129.1 (2C, major), 129.0
(2C, major), 128.9 (2C, minor), 128.8 (2C, minor), 37.2 (minor),
36.3 (major), 28.3 (major), 28.2 (minor), 22.4 (2C, minor), 22.3
(2C, major). HRMS: m/z [M + Na]+ calcd. for C13H15NNaO3
256.0950, found 256.0955.
General procedure for the one-pot synthesis of a-nitro acrylates
and cinnamates 3c,d,j,k (Method B)
To a solution of ethyl nitroacetate (266 mg, 2 mmol) and an
aromatic or aliphatic aldehyde (2.4 mmol) in anhydrous THF
(8 mL), kept at 0 ◦C under Ar in a round-bottom flask containing
˚
previously activated 4 A molecular sieves (5 g), zirconium tetra-
(E/Z)-4-Methyl-2-nitro-1-phenylhex-2-en-1-one (E/Z-7). Iso-
lated yield 75%. Pale yellow oil. Purified by flash chromatography
on silica gel (eluent: hexane/ethyl acetate = 8:2). nmax cm-1 2932,
chloride (932 mg, 4 mmol) was added. The mixtures were kept
stirring at 0 ◦C for 10 min, then a solution of triethylamine (808 mg,
8 mmol) in anhydrous THF (8 mL) was added dropwise for 15 min.
1
1679, 1598, 1530. H NMR (CDCl3, 300 MHz): d 7.90–7.86 (m,
1
The reaction mixtures were refluxed until the H NMR analysis
2H, major isomer), 7.76–7.73 (m, 2H, minor isomer), 7.67–7.61
(m, 2H), 7.54–7.48 (m, 4H), 7.29 (d, J = 11.5 Hz, 1H, major).
6.37 (d, J = 10.5 Hz, 1H, minor), 2.35–2.20 (m, 2H), 1.52–1.42
(m, 4H), 1.16 (d, J = 6.6 Hz, 3H, minor), 1.09 (d, J = 6.6 Hz,
3H, major), 0.86 (t, J = 7.4 Hz, 6H). 13C NMR (CDCl3, 75 MHz):
d 186.9 (2C), 146.8 (major isomer), 146.7 (minor isomer), 135.6
(2C), 134.6 (2C), 133.6 (2C), 129.1 (2C, major), 129.0 (2C, major),
128.9 (2C, minor), 128.8 (2C, minor), 35.5 (minor), 34.5 (major),
29.2 (2C), 19.3 (2C), 11.8 (minor), 11.7 (major). HRMS: m/z [M
+ Na]+ calcd. for C13H15NNaO3 256.0950, found 256.0954.
showed the disappearance of ethyl nitroacetate (see Table 2). The
crude mixtures were filtered through a plug of celite to remove
the molecular sieves using THF as eluent and the solvent was
evaporated under vacuum. Thus, the residues were recovered with
10 mL of Et2O and 15 mL of water were added. After extraction
(three times with diethyl ether), the collected organic layers were
dried over anhydrous Na2SO4 and the solvent was evaporated un-
der vacuum. The products were purified by flash chromatography
on silica gel (eluent: hexane/ethyl acetate = 8:2 for 3c; 9:1 for 3j.
3d was purified using as eluent hexane/dichloromethane = 1:1).
(E/Z)-2,8-Dimethyl-5-nitronon-5-en-4-one
(E/Z-9). Iso-
Ethyl (E/Z)-4-methyl-2-nitrohex-2-enoate (E/Z-3k). Iso-
lated yield 86%. Pale yellow oil. Purified by flash chromatography
on silica gel (eluent: hexane/ethyl acetate = 95:5). nmax cm-1 2932,
1740, 1662, 1530. 1H NMR (CDCl3, 300 MHz): d 7.01 (d, J = 11.2
Hz, 1H, minor isomer), 6.63 (d, J = 11.1 Hz, 1H, major isomer),
4.36 (q, J = 7.1 Hz, 2H, minor), 4.31 (q, J = 7.1 Hz, 2H, major),
2.69–2.54 (m, 1H, minor), 2.44–2.33 (m, 1H, major), 1.58–1.38
(m, 4H), 1.35 (t, J = 7.1 Hz, 3H, minor), 1.32 (t, J = 7.1 Hz,
3H, major), 1.12 (d, J = 6.7 Hz, 3H, minor), 1.10 (d, J = 6.6 Hz,
3H, major), 0.90 (t, J = 7.4 Hz, 3H, minor), 0.88 (t, J = 7.4 Hz,
3H, major). 13C NMR (CDCl3, 75 MHz): d 159.9 (minor isomer),
158.7 (major isomer), 147.4 (2C), 144.4 (2C), 62.6 (major), 62.5
(minor), 35.1 (major), 34.6 (minor), 29.1 (minor), 28.9 (major),
19.2 (minor), 19.0 (major), 13.9 (major), 13.8 (minor), 11.5 (2C).
HRMS: m/z [M + Na]+ calcd. for C9H15NNaO4 224.0899, found
224.0893.
lated yield 93%. Pale yellow oil. Purified by flash chromatography
on silica gel (eluent: hexane/ethyl acetate = 85:15). nmax cm-1
1
2958, 1698, 1653, 1555. H NMR (CDCl3, 300 MHz): d 7.16 (t,
J = 8.1 Hz, 1H, minor isomer), 6.67 (t, J = 7.9 Hz, 1H, major
isomer), 2.50 (d, J = 6.9 Hz, 2H, minor), 2.44 (d, J = 6.8 Hz, 2H,
major), 2.18 (dd, J = 6.9 Hz, 8.1 Hz, 2H, minor), 2.11 (dd, J =
6.9 Hz, 7.8 Hz, 2H, major), 1.88–1.74 (m, 4H), 0.90 (d, J = 6.7
Hz, 12H), 0.89 (d, J = 6.7 Hz, 12H). 13C NMR (CDCl3, 75 MHz):
d 191.1 (minor isomer), 189.9 (major isomer), 153.1 (2C), 137.1
(2C), 46.1 (2C), 36.9 (minor), 36.8 (major), 28.2 (minor), 27.9
(major), 25.3 (minor), 24.9 (major), 24.4 (2C), 24.2 (2C), 22.3
(2C), 22.2 (minor), 22.1 (major). HRMS: m/z [M + Na]+ calcd.
for C11H19NNaO3 236.1263, found 236.1266.
(E/Z)-2,7-Dimethyl-5-nitronon-5-en-4-one
(E/Z-10). Iso-
lated yield 60%. Pale yellow oil. Purified by flash chromatography
on silica gel (eluent: hexane/ethyl acetate = 9:19). nmax cm-1 2957,
1
1698, 1649, 1558. H NMR (CDCl3, 300 MHz): d 6.97 (d, J =
General procedure for the synthesis of conjugated (E/Z)-a-nitro
ketones 6–11
11.4 Hz, 1H, minor isomer), 6.45 (d, J = 10.9 Hz, 1H, major
isomer), 2.55 (d, J = 7.0 Hz, 2H, minor), 2.49 (d, J = 6.9 Hz, 2H,
major), 2.44–2.28 (m, 2H), 2.26–2.10 (m, 2H), 1.52–1.40 (m, 4H),
1.10 (d, J = 6.6 Hz, 3H, major), 1.09 (d, J = 6.8 Hz, 3H, minor),
To a solution of nitro compound 4 or 5 (2 mmol) and an aromatic
or aliphatic aldehyde (2.5 mmol) in CH2Cl2 (5 mL), 2 g of basic
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©

0.95 (d, J = 6.6 Hz, 12H), 0.88 (t, J = 7.5 Hz, 6H). 13C NMR
(CDCl3, 75 MHz): d 190.0 (2C), 147.4 (2C), 142.7 (2C), 46.2
(2C), 35.3 (major isomer), 34.2 (minor isomer), 29.3 (minor), 29.1
(major), 25.0 (major), 24.5 (minor), 22.4 (2C, major), 22.3 (2C,
minor), 19.4 (minor), 19.2 (major), 11.7 (minor), 11.6 (major).
HRMS: m/z [M + Na]+ calcd. for C11H19NNaO3 236.1263, found
236.1269.
5 (a) R. Ballini, E. Marcantoni and M. Petrini, Nitroalkenes as Ami-
nation Tools, In: Amino Group Chemistry: From Synthesis to the Life
Sciences, A. Ricci, Ed., Wiley-VCH, Weinheim, 2008, 93; (b) G. W.
Kabalka and R. S. Varma, Org. Prep. Proced. Int., 1987, 19, 283;
(c) P. Mart´ınez-Bescos, F. Cagide-Fag´ın, F. L. Roa, J. C. Ortiz-Lara,
K. Kierus, L. Ozores-Viturro, M. Ferna´ndez-Gonza´lez and R. Alonso,
J. Org. Chem., 2008, 73, 3745; (d) D. Seebach, G. Calderari and P.
Knochel, Tetrahedron, 1985, 41, 4861.
6 L. Henry, C. R. Hebd. Seances Acad. Sci., 1895, 120, 1265.
7 Rewiews: (a) C. Palomo, M. Oiarbide and A. Laso, Eur. J. Org. Chem.,
2007, 2561; (b) J. Boruwa, N. Gogoi, P. P. Saikia and N. C. Barua,
Tetrahedron: Asymmetry, 2006, 17, 3315; (c) F. A. Luzzio, Tetrahedron,
2001, 57, 915.
8 S. Fioravanti, L. Pellacani, P. A. Tardella and M. C. Vergari, Org. Lett.,
2008, 10, 1449.
9 S. Fioravanti, L. Pellacani and P. A. Tardella, Tetrahedron, 2009, 65,
5747.
10 R. Mohan, N. Rastogi, I. N. N. Namboothiri, S. M. Mobinc and D.
Panda, Bioorg. Med. Chem., 2006, 14, 8073.
11 (a) K. Morita, Z. Suzuki and H. Hirose, Bull. Chem. Soc. Jpn., 1968, 41,
815; (b) A. B. Baylis and M. E. D. Hillman, Ger. Offen., 1972, 2,155,113
(Chem. Abstr., 1972, 77, 34147q); (c) R. O. M. A. de Souza and L.
S. M. Miranda, Mini-Rev. Org. Chem., 2010, 7, 212; (d) M. Guang-
Ning, J. Jia-Jun, S. Min and W. Yin, Chem. Comm., 2009, 37, 5496;
(e) C. Limberakis, Morita-Baylis–Hillman Reaction. Name Reactions
for Homologations, Ed. Ji Jack Li, 2009, Part 1, p 350.
12 N. Rastogi, I. N. N. Namboothiri and M. Cojocaru, Tetrahedron Lett.,
2004, 45, 4745.
13 (a) W. Lehnert, Tetrahedron, 1972, 28, 663; (b) R. S. Fornicola, E.
Oblinger and J. Montgomery, J. Org. Chem., 1998, 63, 3528; (c) S.
Umewaza and S. Zen, Bull. Chem. Soc. Jpn., 1963, 36, 1143.
14 (a) M. T. Shipchandler, Synthesis, 1979, 666; (b) B. Shen and J. N.
Johnston, Org. Lett., 2008, 10, 4397.
(E/Z)-1-(Furan-2-yl)-5-methyl-2-nitrohex-1-en-3-one
(E/Z-
11). Isolated yield 85%. Yellow oil. Purified by flash
chromatography on silica gel (eluent: hexane/ethyl acetate = 8:2).
1
nmax cm-1 2964, 1691, 1634, 1544. H NMR (CDCl3, 300 MHz):
d 7.79 (s, 1H minor isomer), 7.64–7.63 (m, 1H, major isomer),
7.63–7.61 (m, 1H, minor), 7.23 (s, 1H, major), 7.06 (d, J = 3.6 Hz,
1H, minor), 6.95 (d, J = 3.6 Hz, 1H, major), 6.61–6,57 (m, 2H),
2.71 (d, J = 6.7 Hz, 2H, minor), 2.54 (d, J = 6.9 Hz, 2H, major),
2.40–2.17 (m, 2H), 1.02 (d, J = 6.7 Hz, 6H, minor), 0.98 (d, J = 6.7
Hz, 6H, major). 13C NMR (CDCl3, 75 MHz): d 189.7 (2C), 148.2
(2C), 145.3 (2C), 122.4 (2C), 121.8 (minor isomer), 121.2 (major
isomer), 118.1 (2C), 113.8 (minor), 113.4 (major), 51.6 (minor),
45.6 (major), 25.0 (major), 23.9 (minor), 22.4 (2C, major), 22.3
(2C, minor). HRMS: m/z [M + Na]+ calcd. for C11H13NNaO4
246.0742, found 246.0748.
Acknowledgements
We are grateful for financial support from the Italian MIUR
and Universita` degli Studi di Roma “La Sapienza” (PRIN
2007FJC4SF_005).
15 (a) S. Fioravanti, L. Pellacani, P. A. Tardella, A. Morreale and G. Del
Signore, J. Comb. Chem., 2006, 8, 808; (b) S. Fioravanti, A. Morreale,
L. Pellacani and P. A. Tardella, Synlett, 2004, 1083.
16 U. Bora, Synlett, 2003, 1073.
17 V. M. Berestovitskaya, N. I. Aboskalova, E. A. Ishmaeva, S. V.
Bakhareva, G. A. Berkova, Y. A. Vereshchagiva, A. V. Fel’gendler and
G. R. Fattakhova, Russ. J. Gen. Chem., 2001, 71, 1942.
18 F. Textier-Boullet and A. Foucaud, Tetrahedron Lett., 1982, 23, 4927.
19 S. Fioravanti, F. Marchetti, L. Pellacani, L. Ranieri and P. A. Tardella,
Tetrahedron: Asymmetry, 2008, 19, 231.
20 G. P. Sagitullina, L. V. Glizdinskaya and R. S. Sagitullin, Chem.
Heterocycl. Compd., 2005, 41, 739.
21 (a) K. Yamamura, S. Watarai and T. Kinugasa, Bull. Chem. Soc. Jpn.,
1971, 44, 2440; (b) D. L. Boger, R. A. Lerner and B. F. Cravatt, J. Org.
Chem., 1994, 59, 5078.
Notes and references
1 (a) A. G. M. Barrett and G. G. Graboski, Chem. Rev., 1986, 86, 751;
(b) T. A. Alston, D. J. T. Porter and H. J Bright, Bioorg. Chem., 1985, 13,
375; (c) A. G. M. Barrett, Chem. Soc. Rev., 1991, 20, 95; (d) N. Rastogi,
R. Mohan, D. Panda, S. M. Mobinc and I. N. N. Namboothiri, Org.
Biomol. Chem., 2006, 4, 3211; (e) G. W. Kabalka and R. S Varma,
Org. Prep. Proced. Int., 1987, 19, 283 and references therein; (f) Y.
Hoashi, T. Yabuta and Y. Takemoto, Tetrahedron Lett., 2004, 45,
9185.
2 (a) H. H. Baer and L. Urbas, The Chemistry of Amino, Nitroso and Nitro
Compounds and their Derivatives, S. Patai, Ed., John Wiley & Sons,
New York, 1982, Part 2, Chapter 3; (b) R. G. Coombes, Comprehensive
Organic Chemistry, D. Sir Barton and W. D. Ollis Ed., Pergamon Press,
1979, Vol. 2, Part 7; (c) X. Q. Dong, H. L. Teng and C. J. Wang, Org.
Lett., 2009, 11, 1265; (d) P. Gao, C. Wang, Y. Wu, Z. Zhou and C. Tang,
Eur. J. Org. Chem., 2008, 4563; (e) F. X. Chen, C. Shao, Q. Wang, P.
Gong, D. Y. Zhang, B. Z. Zhanga and R. Wanga, Tetrahedron Lett.,
2007, 48, 8456.
22 For a leading review, see: E. N. Jacobsen and M. S. Taylor, Angew.
Chem., Int. Ed., 2006, 45, 3874.
23 (a) M. West-Nielsen, P. M. Dominiak, K. Wozniak and P. E. Hansen,
J. Mol. Struct., 2006, 789, 81; (b) E. Gagnon, T. M. Kenneth, E. Malyz
and J. D. Wuest, Tetrahedron, 2007, 63, 6603.
24 R. Ballini, S. Gabrielli, A. Palmieri and M. Petrini, Curr. Org. Chem.,
2011, 15, 1482.
25 A. R. Katritzky, A. A. A. Abdel-Fattah, A. V. Gromova, R. Witek and
P. J. Steel, J. Org. Chem., 2005, 70, 9211.
3 D. Ranganathan, C. B. Rao, S. Ranganathan, A. K. Mehrotra and R.
Iyengar, J. Org. Chem., 1980, 45, 1185.
26 C. Chun-Li, Z. You-Yun, Z. Jian, S. Xiu-Li, T. Yong, L. Yu-Xue, L.
Guang-Yu and S. Jie, Chem.–Eur. J., 2009, 15, 11384.
27 A. V. Buevich, Y. Wu, T.-M. Chan and A. Stam, Tetrahedron Lett.,
2008, 49, 2132.
28 R. L. Xie and J. R. Hauske, Tetrahedron Lett., 2000, 41, 10167.
29 Z. Shi, B. Tan, W. W. Y. Leong, X. Zeng, M. Lu and G. Zhong, Org.
Lett., 2010, 12, 5402.
4 (a) A. T. Nielsen, J. Org. Chem., 1962, 27, 1998; (b) F. Tur and J.
M. Saa’, Org. Lett., 2007, 9, 5079; (c) Y. Chi, L. Guo, N. A. Kopf
and S. H. Gellman, J. Am. Chem. Soc., 2008, 130, 5608; (d) J. U.
Nef, Justus Liebigs Ann. Chem., 1894, 280, 263; (e) R. Ballini and
M. Petrini, Tetrahedron, 2004, 60, 1017; (f) R. S. Varma, M. Varma and
G. W. Kabalka, Tetrahedron Lett., 1985, 26, 3777; (g) B. Shen and J. N.
Johnston, Org. Lett., 2008, 10, 4397.
30 S. Umezawa, M. Kinoshita and H. Yanagisawa, Bull. Chem. Soc. Jpn.,
1967, 40, 209.
528 | Org. Biomol. Chem., 2012, 10, 524–528
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