Rauhut-Currier type homo- and heterocouplings involving nitroalkenes and nitrodienes

Article abstract of DOI:10.1039/c0ob00062k

Reaction of nitroalkenes or nitrodienes with methyl vinyl ketone (MVK) or acrylate in the presence of the imidazole-LiCl catalyst system provides Rauhut-Currier (vinylogous Morita-Baylis-Hillman) adducts in moderate yield. Under similar conditions (imidaz

Full text of DOI:10.1039/c0ob00062k

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PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Rauhut–Currier type homo- and heterocouplings involving nitroalkenes and
nitrodienes†
Pramod Shanbhag,a Pradeep R. Nareddy,a Mamta Dadwal,a Shaikh M. Mobinb and Irishi N. N. Namboothiri*a
Received 29th April 2010, Accepted 14th July 2010
DOI: 10.1039/c0ob00062k
Reaction of nitroalkenes or nitrodienes with methyl vinyl ketone (MVK) or acrylate in the presence of
the imidazole–LiCl catalyst system provides Rauhut–Currier (vinylogous Morita–Baylis–Hillman)
adducts in moderate yield. Under similar conditions (imidazole–hydroquinone), nitroalkenes and
nitrodienes undergo self-dimerization to afford the Rauhut–Currier adducts in varying yields. An
alternative self-dimerization–nitro group elimination pathway in the presence tricyclohexylphosphine
was observed with heteroaromatic nitroalkenes. A synthetically useful one-pot two step transformation
of Rauhut–Currier adducts of nitroalkenes with MVK to 2,3-disubstituted cyclopentenones is also
described.
Introduction
The phosphine-catalyzed dimerization of activated alkenes, first
disclosed by Rauhut and Currier in their 1963 patent,1 has
set the stage for similar reactions of activated alkenes with
other electrophiles, such as carbonyl compounds and imines, in
the presence of phosphines, amines and analogous nucleophilic
Lewis bases.2 While the latter reaction, popularly known as the
Scheme 1
the RC products in moderate yield. Many of our cross-coupled
Morita–Baylis–Hillman (MBH) reaction, has developed into a
products exhibited tubulin binding anticancer activity at low
highly efficient methodology of topical interest,3,4 the homo- and
micromolar concentrations. More recently, reports on a proline–
NaN3-mediated addition of b-alkyl nitroethylene to enone22 and a
heterodimerization of activated alkenes has not received much
attention, primarily due to the limited substrate scope and poor
selectivity.5
Cinchona alkaloid-catalyzed coupling of b-substituted nitroethy-
lene with cinnamate23 have appeared in the literature. While the
former is a Michael addition that provides a deconjugated RC
product, the latter is a double Michael addition that provides
formal RC products.
According to McClure,6 Baizer and Anderson,7 who inves-
tigated the phosphine-catalyzed dimerization of acrylonitrile,
the mechanism of the Rauhut–Currier (RC) reaction involves
reversible conjugate addition of the phosphine to the activated
alkene followed by conjugate addition of the enolate to another
molecule of activated alkene, proton transfer and elimination.
Later on, Morita and Kobayashi8 followed by McClure,9 Hwu,10
Basavaiah,11 Miller12 and Lee13 reported the cross-coupling re-
action of activated alkenes. Subsequently, phosphine/amine-
catalyzed homodimerization of vinyl ketones,14,15 acrylates,15–17
acrylonitrile,15,17,18 vinyl sulfone and vinyl sulfonate15 has been
reported by various research groups (Scheme 1). Intramolecular,
including asymmetric versions19 and their applications to natural
product synthesis20 have also been reported in recent years.5
We have reported the RC-type coupling of aromatic and het-
eroaromatic conjugated nitroalkenes with other activated alkenes
such as vinyl ketone and acrylate for the first time in 2006.21
Our reaction catalyzed by the imidazole–LiCl system provided
This paper, which is the full version of our preliminary results
on the RC reaction we reported earlier,21 describes for the first
time our studies on similar reactions of aliphatic nitroalkenes
and nitrodienes with enones and acrylates. Furthermore, the
outcome of our attempts to subject nitroalkenes to self-coupling
or RC dimerization is also presented here. A convenient one-
pot transformation of the heterocoupled products to synthetically
useful a,b-disubstituted cyclopentenones is also reported in this
paper.
Results and discussion
First of all, we considered the cross-coupling of a nitroalkene with
another activated alkene such as vinyl ketone. We envisaged that a
nitroalkene, being a powerful acceptor, would undergo conjugate
addition by the nucleophilic Lewis base and the resulting nitronate
would add in a Michael fashion to the enone. Our extensive
optimization studies using 2-nitrovinyl furan 3a and MVK 4a as
the coupling partners in the presence of various nucleophilic Lewis
bases such as DABCO, DBU, DMAP, imidazole etc. revealed
that the desired product 5a would indeed be isolable (Scheme 2).
Although the superior catalytic activity of imidazole vis-a`-vis
other Lewis bases was amply evident from our experiments,
there was further scope for improvement in the yield of the
aDepartment of Chemistry, Indian Institute of Technology Bombay, Mumbai
400 076, India. E-mail: irishi@iitb.ac.in; Fax: +91-22-2576-7152; Tel: + 91-
22-2576-7196
bNational Single Crystal X-Ray Diffraction Facility, Indian Institute of
Technology Bombay, Mumbai 400 076, India
† Electronic supplementary information (ESI) available: Optimization
tables, NMR and X-ray data tables, complete characterization data
and copies NMR spectra. CCDC reference number 788174. For ESI
and crystallographic data in CIF or other electronic format see DOI:
10.1039/c0ob00062k
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Table 2 The RC reaction of aliphatic nitroalkenes 6 with MVK 4a and
ethyl acrylate 4b in the presence of 100 mol% imidazole, and 0.5 M LiCl
in THF at room temperaturea
Scheme 2
coupled product 5a under imidazole-catalyzed conditions. There-
fore, various additives that are capable of activating the enone
via iminium formation, activating the enone and/or nitroalkene
via hydrogen bonding and minimizing the polymerization of these
coupling partners were screened. Since we had only limited success
with hydroquinone as additive, we employed LiCl (0.5 M) in
conjunction with a stoichiometric amount of imidazole in THF for
the cross-coupling of 3a with 4a. This was inspired by the recent
reports on the application of salt to catalyze MBH reactions.24
This catalyst system, which is also reminiscent of the Et3N–LiCl
combination of the Masamune–Roush variant25 of the Horner–
Wadsworth–Emmons reaction, provided the coupled product 5a
in satisfactory (44%) yield in 48 h.21
The above optimized conditions were successfully employed for
the cross-coupling of other heteroaromatic nitroalkenes 3b–3d and
aromatic nitroalkenes 3e–3j with MVK 4a (Table 1, entries 2–10).
It may be noted that although the yields are only moderate in
most cases (28–60%), the reaction was reasonably clean causing
no difficulty whatsoever in the purification and characterization
of the desired products. Since prolonging the reaction time in
many cases caused considerable decomposition of the products,
the reactions were worked up after the specified time, although
some amount of nitroalkene remained.
Entry
6, R
4
7
Time/h
Yield (%)b,c
1
2
3
4
5
6
7
8
6a, i-propyl
6b, n-butyl
6c, n-hexyl
6d, cyclohexyl
6e, norbornenyl
6f, n-butyl
4a
4a
4a
4a
4a
4b
4b
4b
7a
7b
7c
7d
7e
7f
10
16
14
10
8
20
36
24
40
29
35
44
49d
22
27
25
6g, n-hexyl
6h, cyclohexyl
7g
7h
a 3 equiv. of 4 was used. b Isolated yield after purification by silica gel
column chromatography. c 10–20% of 6 was recovered. d E : Z = 1 : 5.
possibility of reacting selected nitroalkenes 3 with ethyl acrylate
4b in a Rauhut–Currier fashion (Table 1, entries 11–14). Although
these efforts were curtailed by prolonged reaction times and
low yields, we were pleased to isolate and characterize the g-
nitroesters 5k–5n which are immediate precursors to g-keto acids
and biologically relevant g-amino acids.
The E geometry of the nitroalkenyl double bond in the RC
adducts 5a–n was evident from the appearance of the proton
b to the NO2 group in the range d 7.85–8.30 in the H NMR
(Table S1, see the ESI†). This was further confirmed by a H–
1H 2D-NOESY experiment on a representative compound, 5e.
Strong NOEs observed between the CH3 groups and one of the
CH2 groups with the aromatic protons together with weak NOEs
observed between the former and the benzylic olefinic proton
supported the above assignment. The structure and geometry of
5e were further unambiguously established by single crystal X-ray
analysis.21
1
1
Having performed the cross-coupling of various aromatic and
heteroaromatic nitroalkenes 3a–j with MVK 4a, we explored the
Table 1 The RC reaction of aromatic nitroalkenes 3 with MVK 4a and
ethyl acrylate 4b in the presence of 100 mol% imidazole, and 0.5 M LiCl
in THF at room temperaturea
Our subsequent endeavors to introduce aliphatic nitroalkenes
6 for the first time as RC coupling partners with MVK 4a and
acrylate 4b provided similar results (Table 2). Since the aliphatic
nitroalkenes were less amenable for prolonged reactions due to
their propensity to undergo polymerization, the reactions in most
cases were performed for less than 24 h. As in the case of aromatic
nitroalkenes 3, RC coupling of aliphatic ones 6 with MVK 4a
(Table 2, entries 1–5) was more impressive than that with acrylate
4b (entries 6–8).
Analogous to the RC adducts 5 arising from aromatic ni-
troalkenes 3, the RC adducts 7 of aliphatic nitroalkenes 6 also
possessed E geometry with the proton b to the nitro group
resonating in the range of d 6.95–7.19 (Table S2, see the ESI†). A
mixture of isomers (1 : 5) was isolated only in the case of RC adduct
7e. Interestingly, the major isomer in this case was assigned Z
geometry based on the shielding of the proton b to the nitro group
in the major isomer as compared to that in the minor isomer by
~0.4 ppm.
Entry
3, Ar
4
5
Time/h
Yield (%)b,c
1
2
3
4
5
6
7
8
3a, 2-furyl
3b, 2-thienyl
3c, 3-furyl
3d, 3-thienyl
3e, Ph
3f, 4-OMe–Ph
3g, 4-Cl–Ph
3h, 3,4-OCH2O–Ph
3i, 3,4-(OMe)2Ph
3j, 4-CF3–Ph
3a, 2-furyl
3e, Ph
3h, 3,4-(OCH2O)Ph
3i, 3,4-(OMe)2Ph
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4b
4b
4b
4b
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
48
50
80
20
72
48
48
48
56
6
56
34
88
90
44
40
36
34
39
41
42
47
60
28
21
18
21
24
9
10
11
12
13
14
Although nitroalkenes have been extensively employed as sub-
strates in Michael addition, cycloadditions26 and other reactions
such as MBH reaction,4 conjugated nitrobutadienes have been
a 3 equiv. of 4 was used. b Isolated yield after purification by silica gel
column chromatography. c 5–23% of 3 was recovered.
4868 | Org. Biomol. Chem., 2010, 8, 4867–4873
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Table 3 The RC reaction of nitrodienes 8 with MVK 4a at room
temperature in the presence of imidazole (100 mol%) and 0.5 M LiCl
in THF at room temperaturea
Table 4 Dimerization of nitroalkenes 3 at room temperature in the
presence of imidazole (50 mol%) and hydroquinone (10 mol%) in CH2Cl2
at room temperature
Entry
3, Ar
10
Time/h
Yield (%)a,b
Entry
8, Ar
9
Time/h
Yield (%)b
1
2
3
4
3a, 2-furyl
3b, 2-thienyl
3c, 3-furyl
10a
10b
10c
10f
24
24
72
48
58
38c
14c
7c
1
2
3
4
8a, Ph
9a
9b
9c
9d
24
10
20
18
33
44
38
40
8b, 2-OMe–Ph
8c, 2-NO2–Ph
8d, 2-furyl
3f, 4-OMe–Ph
a Isolated yield after purification by silica gel column chromatog-
raphy. b 11–32% of was recovered. c Substantial amounts of
trimeric/oligomeric/polymeric materials were also isolated in these cases.
3
a 3 equiv. of 4a was used. b Isolated yield after purification by silica gel
column chromatography.
Under the above optimized conditions, i.e. 50 mol% of imi-
dazole and 10 mol% of hydroquinone in CH2Cl2, several other
nitroalkenes 3a–c and 3f were allowed to dimerize and the results
are summarized in Table 4. It may be noted that although the yield
of the dimer was good (58%) when nitroalkene 3a was used as the
substrate (Table 4, entry 1), it dropped substantially with other
heteroaromatic nitroalkenes 3b and 3c (Table 4, entries 2 and 3,
respectively). The above optimized conditions were ineffective for
aromatic nitroalkenes such as 3f (Table 4, entry 4).
seldom employed in a similar capacity.27 This is despite the fact
that nitrodienes are conveniently accessible via Henry reaction
of a,b-unsaturated aldehydes with nitromethane.28 Therefore, we
decidedtoinvestigate the RC cross-couplingofselected nitrodienes
8, under the optimized conditions, with MVK 4a and were pleased
to isolate the products 9 in moderate yield (Table 3). It may be
noted that the nature of the aromatic ring appears to have some
effect on the yield of the RC product, in that nitrodienes with
relatively electron donating aromatic rings furnished the products
in better yield at shorter reaction times (Table 3, entries 2 and 4).
The geometries of the double bonds in 9a–d were assigned E,E
based on detailed NMR analysis. The protons b to the nitro group
in these isomerically pure products resonated in the range d 7.70–
7.81, suggesting that the a,b-double bond has E configuration
(Table S3, see the ESI†). These protons coupled with the g-protons
with J values in the range of 9.5–11.6 Hz. J values of 15–16 Hz
for the coupling between g- and d-protons suggested that the g,d-
double bond also has E configuration. These assignments were
confirmed by 1H–1H 2D NOESY analysis of a representative
compound 9a. For instance, there was strong NOE between one
of the CH2 groups and the proton g to the nitro group.
The E geometry of the double bond in 10a–c and f was evident
1
from the NMR chemical shift of the H b to the nitro group
(Table S8, see the ESI†). The structure and geometry of 10 were
further unambiguously established by single crystal X-ray analysis
of a representative system, 10a (Fig. 1, see also the Experimental
Section).
Our next objective was to investigate the more challenging self-
or homocoupling of nitroalkenes. Although cyclotrimerization of
nitroalkenes is reported in the literature,29 there has been no report,
to our knowledge, on the dimerization of nitroalkenes presumably
because the major pathway is either cyclotrimerization or linear
oligomerization or polymerization. Our preliminary screening of
various amine-based catalysts such as imidazole, DMAP, DBU,
DABCO, Et3N, Hu¨nig’s base and pyridine for the RC dimerization
of nitrovinyl furan 3a revealed that imidazole was still the only
catalyst that provided the dimer in isolable quantities (Table S4,
see the ESI†). Subsequent solvent screening proved useful as
the reaction proceeded well in CH2Cl2 affording the dimer 10a
in 58% yield in 24 h (Table S5, see the ESI†). The optimum
amount of imidazole was 50 mol% as the reaction was sluggish
with lower quantities and polymerization of nitroalkene 3a was
observed with higher quantities (Table S6, see the ESI†). Further
attempts to improve the yield by screening co-catalysts had only
marginal effect. However, the reaction was cleaner in the presence
of 10 mol% of hydroquinone (Table S7, see the ESI†).
Fig. 1 Single crystal X-ray structure of dimer 10a.
The RC homocoupling of a representative nitrodiene, 8a,
proceeded satisfactorily to provide the dimer 11a in moderate
yield (46%, Scheme 3). The structure and geometry of 11a were
determined by 1H and 13C NMR. The E geometry of the C6–C7
Scheme 3
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double bond was confirmed from the 1H–1H coupling constant of
The structure and stereochemistry of nitrodienes 12 were
unambiguously established by extensive NMR studies on a
representative system 12a (Fig. 2). A coupling of J = 16.4 Hz
between the g- and d-protons confirmed that the g,d double bond
has E geometry. That the a,b double bond is also E, as is evident
from the chemical shift of the g-proton, which experiences a
deshielding effect due to the anisotropic effect of the nitro group.
Unfortunately, appreciable NOE is seen only between the vicinal g-
and d-protons, which is expected. HSQC and HMBC experiments
further confirmed the structure through H–C connectivity (see the
ESI†).
1
15.8 Hz. H–1H J values of 11.7 and 11.2 Hz, respectively, were
indicative of the E geometry for the electron deficient conjugated
double bonds C1–C2 and C3–C4 as well.
The proposed mechanism for the RC homocoupling involves
initial conjugate addition of amine to nitroalkene 3 followed by a
second conjugate addition of the nitronate I to another molecule
of 3 to form intermediate II (Scheme 4). Intramolecular proton
transfer and elimination of the amine would provide the RC
product 10.
Fig. 2 Structure and stereochemistry of 12a (Ar = 2-furyl) by 1H, 13C,
Scheme
troalkenes 3.
4
Formation of RC homocoupled adducts 10 from ni-
APT, 1H–1H COSY, 1H–1H NOESY, HSQC and HMBC experiments.
It is important to note that while the imidazole-mediated
reaction furnished the homodimers 10 and 11 (Table 4, Schemes 3
and 4), the corresponding reaction mediated by phosphine deliv-
ered the elimination product 12. This dichotomous behavior of
nitroalkenes is explained in terms of an alternative elimination
pathway available for the intermediate IV (Scheme 5) which is
analogous to intermediate II in Scheme 4. Here, the elimination of
HNO2 prior to the elimination of phosphine from the intermediate
IV is key to the formation of nitrodiene 12.
Since the scope of RC homocoupling of nitroalkenes under
imidazole-catalyzed conditions appeared limited, we screened
various phosphines and an arsine as catalysts, again by taking
nitroalkene 3a as the model substrate (Table S9, see the ESI†).
Interestingly, instead of the RC dimer, we observed the formation
of an unexpected product which was later identified as nitrodiene
12a (vide infra). Among the catalysts screened, tributyl phosphine
(TBP) and tricyclohexyl phosphine (TCHP) provided the nitro-
diene 12a in comparable yields 77% and 78%, respectively) in 12
h. Further solvent screening and optimization of the amount of
catalyst suggested that the reaction works well in THF with 5 mol%
TCHP (Tables S10–S11, see the ESI†). Substantial polymerization
of nitroalkene 3a was observed when larger quantities of TCHP
were used (Table S11, see the ESI†).
Subsequently, we subjected other aromatic and heteroaromatic
nitroalkenes to the above optimized conditions. The results
presented in Table 5 show that while heteroaromatic nitroalkenes,
with the exception of 3d, smoothly undergo the dimerization–
elimination reaction, nitrostyrene 3e and other aromatic ni-
troalkenes are not amenable for such a transformation.
Table 5 Dimerization of nitroalkenes 3 at room temperature in the
presence of tricyclohexyl phosphine (TCHP) (5 mol%) in THF at room
temperaturea
Scheme 5 Formation of nitrodienes 12 via RC homocoupling and
elimination.
Finally, we investigated some of the possible applications of our
RC adducts. When RC adduct 5e was subjected to tandem metal–
acid reduction–hydrolysis,30 the 1,4-diketone 13e was isolated
in 67% yield (Scheme 6). Much to our delight, basic workup
of the reaction mixture containing 13e led to the formation of
cyclopentenone 14e via intramolecular aldol reaction in 70% yield.
The scope of the above one-pot transformation of RC adduct
5e to substituted cyclopentenone 14e, which involves reduction,
hydrolysis, aldol reaction and dehydration, was subsequently
extended to other RC adducts (Table 6). Thus, selected RC adducts
arising from heteroaromatic and aromatic nitroalkenes 5b, 5f, 5h
Entry
3
Ar
Time
Yield (%)a
1
2
3
4
5
3a
3b
3c
3d
3e
2-furyl
2-thienyl
3-furyl
3-thienyl
Ph
12 h
20 h
12 h
48 h
48 h
79
69b
58b
c
—
—
d
a Isolated yield after purification by silica gel column chromatography.
b Decomposes slowly on repeated purification. c Inseparable mixture of
12d and 3d. d Complex mixture.
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lithium chloride (0.042 mg, 1 mmol), followed by MVK 4a or ethyl
acrylate 4b (3 mmol), and the reaction mixture was stirred at room
temperature. After the completion of the reaction (monitored by
TLC), the reaction mixture was diluted with water (10 ml) and
acidified with 5 N HCl (10 ml). The aqueous layer was extracted
with ethyl acetate (3 ¥ 10 ml), the combined organic layers were
washed with brine (20 ml), dried over anhydrous Na2SO4 and
concentrated in vacuo. The crude residue was purified by silica
gel column chromatography (10% EtOAc–hexane) to afford pure
product 5, 7 or 9.
Scheme 6 Formation of 1,4-diketone 13e and cyclopentenone 14e from
the RC adduct of nitroalkene 5e.
Table 6 Synthesis of substituted cyclopentenones 14 from the RC adducts
of nitroalkenes 5
Representative experimental data.
(E)-7-Methyl-5-nitroocta-5-en-2-one (7a). Yellow oil; Yield 74
mg (40%); nmax (KBr)/cm-1 2965w, 2918 m, 2850w, 1715s, 1523m,
1363m; dH (CDCl3, 400 MHz) 1.11 (6H, d, J 6.7), 2.17 (3H, s),
2.70 (1H, dseptet, J 10.7, 6.7), 2.71 (2H, t, J 7.6), 2.84 (2H, t, J
7.6), 6.95 (1H, d, J 10.7); dC (CDCl3, 100 MHz) 20.7, 22.1, 28.0,
29.9, 41.4, 143.9, 148.7, 206.6; m/z (QTOF ES+, Ar) 208 (MNa+,
100), 205 (7), 149 (10), 99 (7); HRMS (QTOF ES+, Ar) calcd for
C9H15NO3Na (MNa+) 208.0950, found 208.0952.
Entry
Ar
14
Yield (%)a
1
2
3
4
5
5b, Thienyl
5e, Phenyl
5f, 4-OMe–Ph
5h, 3,4-(OCH2O)–Ph
5i, 3,4-(OMe)2–Ph
14b
14e
14f
14h
14i
68
70
74
75
72
General Procedure for the Rauhut–Currier homocoupling of
nitroalkenes or dienes (see Table 4)
a Isolated yield after purification by silica gel column chromatography.
To a stirred solution of nitroalkene 3 or nitrodiene 8 (0.5 mmol)
in CH2Cl2 (1 ml), imidazole (0.017 g, 0.25 mmol, 50 mol%)
and hydroquinone (5 mg, 0.05 mmol, 10 mol%) were added in
one portion. Stirring was continued at room temperature for the
specified time (see Table 4). The crude product was purified by
silica gel column chromatography (5% EtOAc–hexane) to afford
the pure dimer 10 or 11.
and 5i were subjected to the one-pot transformation to afford
cyclopentenones 14b, 14f, 14h and 14i, respectively, in good yield
(Table 6, entries 1, 3–5).
Although such 1,2-disubstituted cyclopentenones possessing a
quaternary benzylic chiral center have been synthesized from 1,4-
diketones,31 a one-pot transformation involving generation of 1,4-
diketone and its intramolecular aldol condensations is hitherto
unreported.32 This is also a convenient alternative to various
other existing methods33,34 for the synthesis of 1,2-disubstituted
cyclopentenones.
Representative experimental data.
2,2¢-(2,4-Dinitrobut-1-ene-1,3-diyl) difuran (10a). Yellow
solid; Yield 40 mg (58%); mp 85–86 ◦C; nmax (KBr)/cm-1 2927
m, 2351w, 1647 m, 1559w, 1371w, 1325m, 1023s; dH (CDCl3, 400
MHz) 5.10 (1H, dd, J 13.7, 6.9), 5.33 (1H, dd, J 13.7, 7.8), 6.14
(1H, dd collapsed to t, J 6.9), 6.23 (1H, d, J 3.2), 6.32 (1H, d, J
1.8), 6.65 (1H, dd collapsed to t, J 1.6), 7.03 (1H, d, J 3.2), 7.33
(1H, s), 7.74 (1H, s), 7.99 (1H, s); dC (CDCl3, 100 MHz) 36.6,
75.5, 107.2, 110.9, 113.4, 123.0, 124.2, 142.1, 142.3, 146.4, 147.8,
148.6; m/z (QTOF ES+, Ar) 301 (MNa+, 100), 232 (42), 218 (35),
186 (5), 79 (8). HRMS (QTOF ES+, Ar) calcd for C12H10N2O6Na
(MNa+) 301.0437, found 301.0442; Selected X-ray data (CCDC
Conclusions
b-Substituted nitroethylenes and d-substituted nitrodienes un-
dergo facile coupling at the a-position with methyl vinyl ketone
(MVK) and ethyl acrylate in the presence of the imidazole–
LiCl catalyst system at room temperature. The nitroalkene–MVK
adducts were transformed to 1,2-disubstituted cyclopentenones
through a one-pot three step sequence involving reduction of the
nitro group, hydrolysis of the enamine and aldol condensation of
the 1,4-diketone. Homocoupling of nitroalkenes and nitrodienes
under similar conditions (imidazole–hydroquinone) provides 1,3-
dinitro compounds, the immediate precursors to 1,3-diamines. A
tandem self-dimerization–elimination providing nitrodienes was
observed when heteroaromatic nitroalkenes were treated with
phosphine catalysts.
¯
788174†) C24H20N4O12, M = 556.44, Triclinic, space group P1, a =
˚
˚
˚
9.0724(4) A, b = 9.7915(4) A,◦c = 14.0849(7) A, a = 89.657(3),
3
˚
b = 77.662(4), g = 82.933(3) , U = 2040.2(4) A , Dc = 1.524
-1
˚
Mg/m3, Z = 2, F(000) = 576, l = 0.71073 A, m = 0.125 mm ,
Total/Unique Reflections = 10904/4233 [R(int) = 0.0271], T =
150(2) K q range = 2.92 to 25.00o, Final R indices [I > 2s(I)]
R1 = 0.0374, wR2 = 0.0818, R indices (all data) R1 = 0.0594, wR2 =
0.0922 (see also Table S12, ESI†).
General procedure for the homocoupling–elimination of
nitroalkenes 3 (see Table 5)
Experimental section
General procedure for the Rauhut–Currier heterocoupling of
nitroalkenes or dienes with MVK or acrylate (see Tables 1–3)
To a stirred solution of nitroalkene 3 (1 mmol) in THF (2 ml),
tricyclohexylphosphine (14 mg, 5 mol%) was added in one portion.
Stirring was continued at room temperature for the specified time
(Table 4). The reaction mixture was concentrated in vacuo and the
To a stirred solution of nitroalkene 3, 6 or nitrodiene 8 (1 mmol)
in THF (2 ml) was added imidazole (0.068 mg, 1 mmol) and
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crude product was purified by silica gel column chromatography
(0–5% EtOAc–hexane) to obtain the nitrodienes 12a–c.
(c) K. Y. Lee, S. Gowrisankar and J. N. Kim, Bull. Korean Chem. Soc.,
2005, 26, 1481; (d) D. Basavaiah, A. J. Rao and T. Satyanarayana, Chem.
Rev., 2003, 103, 811; (e) S. E. Drewes and G. H. P. Roos, Tetrahedron,
1988, 44, 4653; (f) D. Basavaiah, P. D. Rao and R. S. Hyma, Tetrahedron,
1996, 52, 8001; (g) E. Ciganek, Organic Reactions, ed. L. A. Paquette,
John Wiley and Sons, Inc., 1997, Vol. 51.; (h) Y.-L. Shi and M. Shi, Eur.
J. Org. Chem., 2007, 2905; (i) V. Declerck, J. Martinez and F. Lamaty,
Chem. Rev., 2009, 109, 1; (j) G. Masson, C. Housseman and J. Zhu,
Angew. Chem., Int. Ed., 2007, 46, 4614; (k) C. Limberakis, Morita–
Baylis–Hillman Reaction. Name Reactions for Homologations, ed. Ji
Jack Li, 2009, Pt. 1, p 350; (l) V. Carrasco-Sanchez, M. J. Simirgiotis
and L. S. Santos, Molecules, 2009, 14, 3989; (m) G.-N. Ma, J.-J. Jiang,
M. Shi and Y. Wei, Chem. Commun., 2009, 5496; (n) Y. Wei and M. Shi,
Acc. Chem. Res., 2010, 43, 1005.
4 For our reports on the MBH reaction of nitroalkenes with various
electrophiles. Formaldehyde: (a) N. Rastogi, I. N. N. Namboothiri and
M. Cojocaru, Tetrahedron Lett., 2004, 45, 4745; (b) R. Mohan, N.
Rastogi, I. N. N. Namboothiri, S. M. Mobin and D. Panda, Bioorg.
Med. Chem., 2006, 14, 8073. Other carbonyl compounds: (c) I. Deb,
M. Dadwal, S. M. Mobin and I. N. N. Namboothiri, Org. Lett., 2006, 8,
1201; (d) I. Deb, P. Shanbhag, S. M. Mobin and I. N. N. Namboothiri,
Eur. J. Org. Chem., 2009, 4091. Activated imines/iminiums: (e) N.
Rastogi, R. Mohan, D. Panda, S. M. Mobin and I. N. N. Namboothiri,
Org. Biomol. Chem., 2006, 4, 3211; (f) K. Rajesh, P. Shambhag, M.
Raghavendra, P. Bhardwaj and I. N. N. Namboothiri, Tetrahedron Lett.,
2010, 51, 846. Azodicarboxylates: (g) M. Dadwal, S. M. Mobin and I.
N. N. Namboothiri, Org. Biomol. Chem., 2006, 4, 2525.
Representative experimental data.
2-((1E,3E)-3-(Furan-2-yl)-4-nitrobuta-1,3-dienyl)furan (12a).
Yellow crystalline solid; Yield 90 mg (79%); mp 52–54 ◦C; nmax
(KBr)/cm-1 2921s, 1613m, 1586m, 1556w, 1318m, 1092m, 1021s,
804m; dH (CDCl3, 400 MHz) 6.49 (1H, dd, J 3.4, 1.8), 6.58 (2H,
dd, J 3.4, 1.8), 6.86 (1H, d, J 3.4), 7.00 (1H, d, J 16.4), 7.43
(1H, d, J 0.6), 7.54 (1H, d, J 1.5), 7.61 (1H, d, J 1.5), 7.92 (1H,
dd, J 16.4, 0.6); dC (CDCl3, 100 MHz) 112.6, 112.9, 113.9, 117.4,
119.3, 128.8, 131.5, 137.2, 144.9, 145.9, 148.8, 152.0; m/z (QTOF
ES+, Ar) 232 (MH+, 100%), 187 (44), 185 (38), 158 (10), 129 (3);
HRMS (QTOF ES+) calcd for C12H10NO4 (MH+) 232.0610, found
232.0600. Confirmed by COSY, NOESY, HSQC and HMBC.
General procedure for the synthesis of substituted cyclopentenone
14 (see Table 6)
To a solution of RC adduct 5 (1 mmol) in a mixture of MeOH
(1.7 ml), H2O (0.7 ml) and conc. HCl (0.7 ml), iron dust
(112 mg, 2 mmol) was added in portions and the resulting
reaction mixture was heated over a water bath for 30 min. After
complete disappearance of starting material (monitored by TLC),
the reaction mixture was cooled to room temperature, diluted with
MeOH (10 ml) and filtered through a bed of Celite. The filtrate was
concentrated in vacuo, the residue was diluted with water (10 ml),
basified with 10% NaOH (10 ml) and extracted with ethyl acetate
(3 ¥ 10 ml). The combined organic layers were washed with brine
(10 ml), concentrated in vacuo and the residue was purified by silica
gel column chromatography by eluting with a ethyl acetate–pet.
ether mixture (10–20%) to afford pure cyclopentenone 14. Note:
neutral workup of the reaction mixture, i.e. without using 10%
NaOH (10 ml) provided 1,4-diketone 13 (see Scheme 6).
5 For the only comprehensive review: (a) C. E. Aroyan, A. Dermenci and
S. J. Miller, Tetrahedron, 2009, 65, 4069 and the references cited therein.
See also: (b) J. L. Methot and W. R. Roush, Adv. Synth. Catal., 2004,
346, 1035.
6 J. D. McClure, U.S. Patent, 1965, 3225083.
7 M. M. Baizer and J. D. Anderson, J. Org. Chem., 1965, 30, 1357.
8 Between methyl acrylate and acrylonitrile with fumaric/maleic esters:
K. Morita and T. Kobayashi, Bull. Chem. Soc. Jpn., 1969, 42, 2732.
9 Between ethyl acrylate and acrylonitrile: J. D. McClure, J. Org. Chem.,
1970, 35, 3045.
10 Enone with acrylate, acrylonitrile and sulfone: J. R. Hwu, G. H.
Hakimelahi and C.-T. Chou, Tetrahedron Lett., 1992, 33, 6469. The
same authors proposed a Michael addition of the dienoate generated
from the b-alkyl enone by the base to the desired activated alkene as
the pathway, rather than the RC pathway.
11 Acrylonitrile with a-halomethyl acrylate and vinyl ketone: (a) D.
Basavaiah, N. Kumaragurubaran and D. S. Sharada, Tetrahedron
Lett., 2001, 42, 85. Acrylate, acrylonitrile and vinyl ketone with a-
bromomethyl acrylate: (b) D. Basavaiah, D. S. Sharada, N. Kumaragu-
rubaran and R. M. Reddy, J. Org. Chem., 2002, 67, 7135.
12 Allenoate with enone: C. A. Evans and S. J. Miller, J. Am. Chem. Soc.,
2003, 125, 12394.
Representative experimental data.
2-(3,4-Dimethoxyphenyl)-3-methylcyclopent-2-enone
(14i).
Red liquid; Yield 167 mg (72%); nmax(film)/cm-1 2964s, 2939s,
2879s, 1725s, 1516w, 1466w, 1376w, 1257s, 1053m, 1017w, 968m;
dH (CDCl3, 400 MHz) 2.20 (3H, s), 2.48–2.60 (2H, m), 2.60–2.72
(2H, m), 3.90 (3H, s), 3.92 (3H, s), 6.82–6.95 (3H, m); dC (CDCl3,
100 MHz) 18.6, 31.9, 35.0, 56.0 (¥ 2), 111.2, 112.5, 121.9,
124.6, 140.1, 148.7, 148.8, 171.5, 208.2; m/z (QTOF ES+) 233
(MH+, 100); HRMS (QTOF ES+, Ar) calcd for C14H17O3 (MH+)
233.1178, found 233.1174.
13 MVK and acrylate with dihalonaphthoquinones: C. H. Lee and K.-J.
Lee, Synthesis, 2004, 1941.
14 (a) H. Amri and J. Villieras, Tetrahedron Lett., 1986, 27, 4307; (b) D.
Basavaiah, V. V. L. Gowriswari and T. K. Bharathi, Tetrahedron Lett.,
1987, 28, 4591; (c) S. E. Mc Dougal and S. E. Schaus, Angew. Chem.,
Int. Ed., 2006, 45, 3117.
15 P. T. Kaye and X. W. Nocanda, J. Chem. Soc., Perkin Trans. 1, 2002,
1318.
16 (a) H. Amri, M. Rambaud and J. Villieras, Tetrahedron Lett., 1989, 30,
7381; (b) S. E. Drewes, N. D. Emslie and N. Karodia, Synth. Commun.,
1990, 20, 1915.
Acknowledgements
The authors thank DST, India for funding, SAIF, IIT Bombay
and Mr Uday Prabhu, IISc Bangalore for selected NMR data. PS
and MD thank CSIR, India for research fellowship.
17 G. Jenner, Tetrahedron Lett., 2000, 41, 3091.
18 D. Basavaiah, V. V. L. Gowriswari, P. Dharma Rao and T. K. Bharathi,
J. Chem. Res. (S), 1995, 267.
19 Intramolecular: (a) J. K. Erguden and H. W. Moore, Org. Lett., 1999,
1, 375; (b) P. M. Brown, N. Kappel and P. J. Murphy, Tetrahedron Lett.,
2002, 43, 8707; (c) P. M. Brown, N. Kappel, P. J. Murphy, S. J. Koles
and M. B. Hursthouse, Tetrahedron, 2007, 63, 1100; (d) L. C. Wang, A.
L. Luis, K. Agapiou, H. Y. Jang and M. J. Krische, J. Am. Chem. Soc.,
2002, 124, 2402; (e) A. L. Luis and M. J. Krische, Synthesis, 2004, 15,
2579; (f) S. A. Frank, D. J. Mergott and W. R. Roush, J. Am. Chem.
Soc., 2002, 124, 2404; (g) R. K. Thalji and W. R. Roush, J. Am. Chem.
Soc., 2005, 127, 16778; (h) F. O. Seidel and J. A. Gladysz, Adv. Synth.
Catal., 2008, 350, 2443. Intramolecular asymmetric: (i) C. E. Aroyan
and S. J. Miller, J. Am. Chem. Soc., 2007, 129, 256; (j) F. O. Seidel and
J. A. Gladysz, Synlett, 2007, 986.
Notes and references
1 M. M. Rauhut and H. Currier, U.S. Patent, 1963, 3074999; Chem.
Abstr., 1963, 58, 11224a.
2 (a) K. Morita, Z. Suzuki and H. Hirose, Bull. Chem. Soc. Jpn., 1968,
41, 2815; (b) A. B. Baylis, M. E. D. Hillman, Ger. Offen., 1972, DE
2155113; Chem. Abstr., 1972, 77, 434174; M. E. D. Hillman, A. B.
Baylis, US Pat., 1973, US 3743669.
3 Reviews: (a) V. Singh and S. Batra, Tetrahedron, 2008, 64, 4511; (b) D.
Basavaiah, K. V. Rao and R. J. Reddy, Chem. Soc. Rev., 2007, 36, 1581;
4872 | Org. Biomol. Chem., 2010, 8, 4867–4873
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20 For recent selected examples: (a) P. Webber and M. J. Krische, J.
Org. Chem., 2008, 73, 9379; (b) S. M. Winbush, D. J. Mergott and
W. R. Roush, J. Org. Chem., 2008, 73, 1818; (c) L. M. Stark, K.
Pekari and E. J. Sorensen, Proc. Natl. Acad. Sci. U. S. A., 2004, 101,
12064.
21 M. Dadwal, R. Mohan, D. Panda, S. M. Mobin and I. N. N.
Namboothiri, Chem. Commun., 2006, 338. Although we called this
reaction a Morita–Baylis–Hillman (MBH) reaction, according to the
present classification (see ref. 5), this vinylogous MBH reaction is more
appropriately called a Rauhut–Currier (RC) reaction.
27 For the Michael addition of aldehydes to nitrodienes: (a) S. Belot,
A. Massaro, A. Tenti, A. Mordini and A. Alexakis, Org. Lett., 2008,
10, 4557; (b) For the MBH reaction of nitrodienes with carbonyl
compounds: see ref. 4d.
28 (a) C. Dockendorff, S. Sahhli, M. Olsen, L. Milhau and M. Lautens,
J. Am. Chem. Soc., 2005, 127, 15028; (b) N. K. Kochetkov and N. V.
Dubikina, J. Gen. Chem. USSR, 1958, 28, 2473.
29 (a) T. Y. Kim, H. S. Kim, K. Y. Lee and J. N. Kim, Bull. Kor. Chem.
Soc., 1999, 20, 1255; (b) T. Y. Kim, H. S. Kim, K. Y. Lee and J. N. Kim,
Bull. Kor. Chem. Soc., 2000, 21, 521.
22 X. Sun, S. Sengupta, J. L. Peterson, H. Wang, J. P. Lewis and X. Shi,
Org. Lett., 2007, 9, 4495.
30 For a recent procedure: P. K. Pradhan, Sumit Dey, P. Jaisankar and V.
S. Giri, Synth. Commun., 2005, 35, 913.
23 J. Wang, H. Xie, L. Zu and W. Wang, Angew. Chem., Int. Ed., 2008, 47,
31 (a) M. Yuguchi, M. Tokuda and K. Orito, J. Org. Chem., 2004, 69,
908; (b) A. Pecunioso and R. Menicagli, J. Org. Chem., 1988, 53, 2614;
(c) H. Stetter and G. Lorenz, Chem. Ber., 1985, 118, 1115.
32 For a one-pot synthesis of cyclopentenones via conjugate addition
of primary nitroalkanes to a,b-unsaturated ketones followed by Nef
reaction and aldol condensation: R. Ballini, L. Barboni, G. Bosica and
D. Fiorini, Synthesis, 2002, 2725.
33 By Pauson–Khand reaction, selected reviews: (a) N. E. Schore, Organic
Reactions, 1991, 40; (b) T. Shibata, Adv. Synth. Catal., 2006, 348, 2328;
(c) S. Laschat, A. Becheanu, T. Bell and A. Baro, Synlett, 2005, 2547;
(d) S. E. Gibson and N. Mainolfi, Angew. Chem., Int. Ed., 2005, 44, 3022;
(e) J. Blanco-Urgoiti, L. Anorbe, L. Perez-Serrano, G. Dominguez and
J. Perez-Castells, Chem. Soc. Rev., 2004, 33, 32;(f) M. R. Rivero, J. Adrio
and J. C. Carretero, Eur. J. Org. Chem., 2002, 2881; (g) T. Sugihara, M.
Yamaguchi and M. Nishizawa, Chem.–Eur. J., 2001, 7, 1589.
34 By zirconium promoted intermolecular coupling of an alkyne, EtMgBr
or ethylene, and CO: (a) T. Takahashi, Z. Xi, Y. Nishihara, S. Huo, K.
Kasai, K. Aoyagi, V. Denisov and E. Negishi, Tetrahedron, 1997, 53,
9123. By Ramberg-Ba¨cklund reaction: (b) G. Casy and R. J. K. Taylor,
Tetrahedron, 1989, 45, 455. By cycloreversion reaction: (c) G. Stork, G.
L. Nelson, F. Rouessac and O. Gringore, J. Am. Chem. Soc., 1971, 93,
3091.
4177.
24 (a) V. K. Aggarwal, D. K. Dean, A. Mereu and R. Williams, J. Org.
Chem., 2002, 67, 510; (b) A. Kumar and S. S. Pawar, Tetrahedron, 2003,
59, 5019.
25 (a) M. A. Blanchette, W. Choy, J. T. Davis, A. P. Essenfeld, S. Masamune,
W. R. Roush and T. Sakai, Tetrahedron Lett., 1984, 25, 2183. See also:
(b) J. J. Li, Name Reactions, Springer (India) Pvt. Ltd., New Delhi, 2nd
edn, 2003.
26 For selected reviews: (a) I. N. N. Namboothiri and N. Rastogi, Top.
Heterocycl. Chem., 2008, 12, 1; (b) R. Ballini, L. Barboni, G. Bosica,
D. Fiorini and A. Palmieri, Pure Appl. Chem., 2006, 78, 1857; (c) O. M.
Berner, L. Tedeschi and D. Enders, Eur. J. Org. Chem., 2002, 1877; (d) I.
N. N. Namboothiri and A. Hassner, Top. Curr. Chem., 2001, 216, 1;
(e) S. E. Denmark and A. Thorarensen, Chem. Rev., 1996, 96, 137; (f) V.
V. Perekalin, E. S. Lipina, V. M. Berestovitskaya, and D. A. Efremov,
Nitroalkenes: Conjugated Nitro Compounds, Wiley, Chichester, UK,
1994, p 1; (g) Nitroalkanes and Nitroalkenes in Synthesis, Tetrahedron
Symposia-in-Print, No. 41, ed. A. G. M. Barrett, in: Tetrahedron, 1990,
46, 285; (h) G. W. Kabalka and R. S. Varma, Org. Prep. Proced. Int.,
1987, 19, 283; (i) D. Seebach, E. W. Colvin, F. Lehr and T. Weller,
Chimia, 1979, 33, 1.
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The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 4867–4873 | 4873
©