Unprecedented synthesis of 3-alkenyl-3-ethoxy-2-iminoketones via 1,3-dipolar cycloadditions of nitrones with alkynyl Fischer carbene complexes

Article abstract of DOI:10.1021/om400420c

The synthesis of novel and highly substituted (2Z,3Z)-3-ethoxy-1-(aryl/ cyclohexenyl)-4-aryl-2-(phenylimino)but-3-en-1-one derivatives 24a-k and 27a-e by an unexpected and previously unreported [3 + 2] cycloaddition/rearrangement and ring-opening cascade process of the Fischer carbene complexes (CO) ₅M=C(Ci -C-Ar)OCH₂CH₃ 1a-c (M = Cr) and 1d-f (M = W) and (CO)₅M=C(Ci -C-cyclohexenyl)OCH ₂CH₃ 23a (M = Cr) and 23b (M = W) with C,N-diaryl nitrones (7a-f) is described. It is likely that the unstable 2,3-dihydroisoxazole carbene complexes produced in the [3 + 2] cycloaddition undergo a rapid and new rearrangement, followed by a stereoselective electrocyclic ring-opening process at a low temperature, to give only the (Z,Z) diastereoisomers 24a-k and 27a-e as the isolated products. The stereochemical assignment of the products was supported by NOE measurements and by single-crystal X-ray diffraction.

Full text of DOI:10.1021/om400420c

Article
pubs.acs.org/Organometallics
Unprecedented Synthesis of 3‑Alkenyl-3-ethoxy-2-iminoketones via
1,3-Dipolar Cycloadditions of Nitrones with Alkynyl Fisher Carbene
Complexes
María Ines Flores-Conde,† Miguel Angel Vazquez,‡ Leonor Reyes,† Joaquín Tamariz,†
́
́
and Francisco Delgado*,†
†Departamento de Química Organ
Ayala, 11340 Mexico, D. F., Mexico
́ ́
ica, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Prol. Carpio y Plan de
‡Departamento de Química, Universidad de Guanajuato, Noria Alta S/N, 36050 Guanajuato, Gto., Mexico
S
* Supporting Information
ABSTRACT: The synthesis of novel and highly substituted
(2Z,3Z)-3-ethoxy-1-(aryl/cyclohexenyl)-4-aryl-2-
(phenylimino)but-3-en-1-one derivatives 24a−k and 27a−e by
an unexpected and previously unreported [3 + 2] cyclo-
addition/rearrangement and ring-opening cascade process of
the Fischer carbene complexes (CO)5MC(CC−Ar)-
OCH2CH3 1a−c (M = Cr) and 1d−f (M = W) and
(CO)5MC(CC-cyclohexenyl)OCH2CH3 23a (M = Cr)
and 23b (M = W) with C,N-diaryl nitrones (7a−f) is
described. It is likely that the unstable 2,3-dihydroisoxazole carbene complexes produced in the [3 + 2] cycloaddition undergo a
rapid and new rearrangement, followed by a stereoselective electrocyclic ring-opening process at a low temperature, to give only
the (Z,Z) diastereoisomers 24a−k and 27a−e as the isolated products. The stereochemical assignment of the products was
supported by NOE measurements and by single-crystal X-ray diffraction.
dihydroisoxazoles is carried out by their rearrangement
reaction.7 Several experimental8−10 and theoretical11 studies
have been performed on the application of nitrones in 1,3-
dipolar cycloadditions with the highly electrophilic C−C triple
bond of alkynyl Fischer carbene complexes. In one of these
reports, Kalinin et al.8 have shown that the 1,3-dipolar
cycloaddition reaction of trimethylsilylethynyl carbene com-
plexes of Cr(0) and W(0) 6a,b with C,N-diphenyl nitrone 7
gave the 2,3-dihydrooxazole carbene complexes 9a,b, resulting
from the rearrangement of the unstable 2,3-dihydroisoxazole
carbene complexes 8a,b. These interesting findings were
however limited to these substrates (Scheme 2).
INTRODUCTION
■
Since the discovery of metal−carbene complexes by E. O.
Fischer in 1964,1 these have been demonstrated to be excellent
partners for different reactions and have been repeatedly used
in the synthesis of new organic and organometallic com-
pounds.2 Alkenyl and alkynyl Fischer carbene complexes of
group 6 are of particular interest, because they can be involved
in diverse cycloaddition reactions that offer access to
heterocyclic and carbocyclic rings. Moreover, they can readily
undergo novel cascade processes or unique rearrangement
reactions,3 making them fascinating substrates from both
synthetic and mechanistic points of view.
For example, these carbene complexes can lead to the
synthesis of cis-1,3,5-metallahexatrienes, which are potentially
amenable to a number of synthetic transformations.4 Recently,
we reported an unusual behavior of alkynyl Fischer carbene
complexes 1 toward pentamethylcyclopentadiene 2 under
thermal conditions.5 The cis-1,3,5-metallahexatrienes 3a−c,
formed from this initial Diels−Alder reaction, were involved
in the formation of the benzannulation product as well as its
subsequent rearrangement to yield the 1,2- and 1,4-
naphthofurandiones 4 and 5 (Scheme 1).
In another study, Chan et al.9b reported the generation of
2,3-dihydroisoxazole carbene complexes 13−19 through highly
regioselective 1,3-dipolar reactions of phenylethynyl carbene
complexes 1 with the C-aryl-N-alkyl nitrones 10−12 (Scheme
3). However, all attempts to perform the 2,3-dihydroisoxazole-
dihydrooxazole carbene complex rearrangement were unsuc-
cessful, obtaining only the oxidation product of the
corresponding [3 + 2] cycloadduct 13−19.
Barluenga et al.10a extended this study to alkylethynyl
carbenes, reporting that the reaction of tert-butylethynyl
carbene complex 20 with C-aryl-N-methyl nitrones 10 yielded
similar results to those reported by Chan.9b However, they
On the other hand, 2,3-dihydroisoxazoles are a class of
compounds endowed with a broad range of interesting
reactivity patterns. They are accessible by 1,3-dipolar cyclo-
addition of nitrones (as dipoles) with acetylenecarboxylates (as
dipolarophiles).6 One of the important transformations of 2,3-
Received: May 13, 2013
© XXXX American Chemical Society
A
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Scheme 1
Scheme 2
Scheme 3
Scheme 4
noted that the resulting adducts 21 decomposed to the
respective β-enaminoketoaldehydes 22 after several days and
that exposure to sunlight accelerated this rearrangement
(Scheme 4).
The aforementioned results prompted us to study the [3 + 2]
cycloaddition reaction between the C,N-diaryl nitrones 7a−f
and several activated aryl- and cyclohexenylethynyl carbene
complexes, 1a−f and 23a,b, to better understand the factors
controlling these pathways. To the best of our knowledge, no
systematic study has been carried out in relation to the
influence of the N-aryl substituent in the nitrones on the course
of these reactions.
We herein report an unprecedented [3 + 2] cycloaddition/
rearrangement and ring-opening cascade process of alkynylcar-
bene complexes with substituted C,N-diaryl nitrones, providing
an efficient and stereoselective approach to highly substituted
(2Z,3Z)-3-ethoxy-1-(aryl/cyclohexenyl)-4-aryl-2-
(phenylimino)but-3-en-1-one derivatives 24 and 27. In
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addition, we evaluated the substituent effect of the aromatic
rings, in both 1,3-dipoles and carbene complexes, on the
reactivity as well as the regio- and stereoselectivity of this
cascade process. Finally, derivatization of compound 24b was
carried out by reacting with 2,4-dinitrophenylhydrazine (33) to
produce a mixture of chemoisomeric hydrazones 34 and 35.
In an attempt to further improve the adduct yield, the
reaction was started at a low temperature (−78 °C), and then
the mixture was allowed to slowly warm to room temperature
for ∼4 h. Under these reaction conditions, not only was adduct
24a obtained in a better yield (57%) (Table 1, entry 1) but the
decomposition of nitrone and formation of β-phenylamino
carbene 25 was inhibited.
RESULTS AND DISCUSSION
To validate this new process and to evaluate the substituent
effect of R and R1 in 1,3-dipoles and dipolarophiles, as well as to
assess the possible effect of the metal on the reactivity and
stereoselectivity of the reaction, a series of reactions were
carried out under the same conditions using diverse substituted
starting materials (Table 1).
■
[3 + 2] Cycloaddition. The starting compounds
(pentacarbonyl)(alkynyl)(ethoxy)carbene chromium(0) and
tungsten(0) complexes 1a−f and 23a,b and C,N-diaryl nitrones
7a−f were prepared by the standard methods previously
reported12,13 (Figure 1).
When C,N-diaryl nitrones 7b,c, bearing an electron-releasing
group (R1 = 4-OMe, R1 = 3,4,5-OMe), were reacted with
carbene complex 1a, the conversion rate slightly increased
(Table 1, entries 2 and 3), obtaining 24b and 24c, respectively,
in higher yields. However, when reacting nitrones 7d,e
(substituted with an electron-withdrawing group) with carbene
complex 1a, a lower conversion to the corresponding product
took place (Table 1, entries 4, 5).
We decided to evaluate the effect of the substituent in the
aromatic ring of the carbene complexes. Thus, carbenes 1b and
1c were reacted with nitrone 7b (Table 1, entries 6 and 10)
with the result that 1c reacted slower and produced a lower
yield of 24j than 1b. At first, we considered that this behavior
was due to a decreased reactivity caused by the strong electron-
releasing effect of the methoxy group in 1c.14 However, this
apparent cause was later found not to be the most significant, as
evidenced by the fact that the reaction with 7b was slower for
carbene 1a than 1b and occurred at a similar rate for 1b and 1c
(Table 1, entries 2, 6, and 10). Actually, these three carbenes
reacted with nitrone 7e in identical reaction times and in similar
yields (Table 1, entries 5, 8, and 11).
Finally, with the aim of exploring the scope and limitations of
the process, as well as of detecting the effect on the substituent
in the carbene complexes, the cyclohexenylethynyl carbene
complexes 23a (M = Cr) and 23b (M = W) were reacted with
various dipoles 7, under conditions identical to those used for
reacting 1a−f. The cycloaddition reactions employing 23a,b
yielded products 27a−e as a single Z,Z-isomer, respectively
(Table 2, entries 1−8).
Figure 1.
The (arylethynyl)(ethoxy)carbene complexes 1a−f were
evaluated in terms of reactivity and selectivity toward C,N-
diphenyl nitrones 7a−e in [3 + 2] cycloaddition reactions.
Initially, a mixture of the phenylethynyl carbene 1a (1.0 molar
equiv) and C,N-diaryl nitrone 7a (1.0 molar equiv) was reacted
in dry THF at room temperature, until a color change (from
red to green in ∼30 min) took place in the solution. After
workup, an unexpected and new (2Z,3Z)-3-ethoxy-1-(phenyl)-
4-phenyl-2-(phenylimino)but-3-en-1-one (24a) was obtained
in moderate yield (30%). β-Phenylamino carbene 25 and
benzaldehyde 26 were also detected in the reaction mixture
(Scheme 5), which probably stemmed from the descomposi-
tion of nitrone 7a. Thus, through the latter process a molecule
of the respective aniline was generated, followed by a
conjugated addition to the carbene 1a to afford 25. The
structural characterization of product 24a was made on the
basis of spectroscopic analysis.
Since cycloadducts 24a−k and 27a−e were obtained as a
single Z,Z-isomer with comparable reaction times and yields
(Tables 1 and 2), the reactivity and selectivity of carbene
complexes of W(0) 1d−f and 23b are similar to those found for
the carbenes of Cr(0) 1a−c and 23a, suggesting a negligible
effect between chromium and tungsten metal atoms during the
process.
In contrast to the previously reported approach,8,9b,10a it was
interesting and surprising that the reaction did not afford either
the expected [3 + 2] cycloadducts 13−19 or the rearranged
cycloadduct 9. Rather, novel compound 24a was obtained in a
moderate yield.
The structural characterization of the isolated products 24
and 27 was made by spectroscopic data. For instance, high-
Scheme 5
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Table 1. Reaction Conditions and Yields in the Cascade Process of Phenylethynyl Carbenes 1a−f with C,N-Diphenyl Nitrones
a
7a−e
b
entry
carbene
M
nitrone
R
R1
reaction time (h)
adduct
yield (%)
1
1a
1a
1a
1a
1a
1b
1b
1b
1c
1c
1c
1d
1d
1e
1e
1f
Cr
Cr
Cr
Cr
Cr
Cr
Cr
Cr
Cr
Cr
Cr
W
W
W
W
W
W
7a
7b
7c
7d
7e
7b
7d
7e
7a
7b
7e
7a
7e
7b
7d
7a
7b
H
H
H
H
H
H
3.5
3.0
2.0
2.5
4.0
2.0
3.5
4.0
3.5
3.0
4.0
3.5
4.0
3.5
4.0
2.0
3.0
24a
24b
24c
24d
24e
24f
24g
24h
24i
57
70
75
55
44
60
47
40
55
45
40
50
42
53
45
55
40
2
4-OMe
3,4,5-OMe
4-Cl
3
4
5
4-NO2
4-OMe
4-Cl
6
4-Me
4-Me
4-Me
4-OMe
4-OMe
4-OMe
H
7
8
4-NO2
H
9
10
11
12
13
14
15
16
17
4-OMe
4-NO2
H
24j
24k
24a
24e
24f
24g
24i
H
4-NO2
4-OMe
4-Cl
4-Me
4-Me
4-OMe
4-OMe
H
1f
4-OMe
24j
a
b
All entries were carried out with a 1 molar equiv of 1 and 7 in dry THF, beginning at −78 °C and slowly warming to rt. After column
chromatography.
Table 2. Conditions and Yields in the Cascade Reaction of Cyclohexenylethynyl Carbenes 23a,b with C,N-Diphenyl Nitrones
a
7a,b and 7d−f
b
entry
carbene
M
nitrone
R1
reaction time (h)
adduct
yield (%)
1
2
3
4
5
6
7
8
23a
23a
23a
23a
23b
23b
23b
23b
Cr
Cr
Cr
Cr
W
W
W
W
7a
7b
7e
7f
H
2.5
2.0
4.0
4.0
3.0
3.0
3.0
3.5
27a
27b
27d
27e
27a
27b
27c
27d
45
53
40
36
35
45
37
40
4-OMe
4-NO2
3-NO2
H
7a
7b
7d
7e
4-OMe
4-Cl
4-NO2
a
b
All entries were carried out with a 1 molar equiv of 23 and 7 in dry THF, beginning at −78 °C and slowly warming to rt. After column
chromatography.
resolution mass spectrometry (HRMS) of 24i showed the
expected mass (m/z 385.1695), while the infrared spectrum
displayed characteristic absorptions at 1600 (CN), 1565
(CO), and 1262 cm−1 (CC-OEt). The 1H NMR spectrum
showed the presence of 14 aromatic protons at 7.78−6.78 ppm,
two singlets at 6.33 and 3.77 ppm identified as the methine (H-
4) and methoxy (OMe) groups, respectively, and a quartet and
a triplet at 4.22 and 1.40 ppm integrating for two and three
protons of the ethoxycarbonyl group, respectively. The 13C
NMR spectrum displayed signals at 194.8 and 164.9 ppm due
to the carbonyl and imino groups, respectively, as well as two
signals at 151.6 and 126.4 ppm for the vinyl carbons of the enol
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moiety, 12 signals at 164.3−114.0 ppm for aromatic carbons,
and three signals at 67.9, 55.4, and 15.6 ppm for sp3 carbon
atoms. In the 13C NMR spectra, it is interesting to note the
low-field chemical shifts of the vinylic carbon (C-4) in all
adducts (∼149.0−154.0 ppm). This indicates that the electron-
donating effect of the ethoxy group does not shield the vinyl β-
carbon or its associated proton. This may be due to the
presence of the aryl group cis to the ethoxy group, which
prevents coplanarity between the oxygen lone pairs and the
double bond (see Figure 3). Assignment of all signals in the 1H
configuration, and consequently the imino carbon (C-2)−
nitrogen double bond has a Z configuration.
Single-crystal X-ray diffraction crystallography of compound
24i allowed us to confirm its structure (Figure 3). It exhibits the
2Z,3Z configuration of the backbone N(9)−C(2)−C(3)−C(4)
in an s-trans conformation [C(3)−C(4)−C(5)−C(6) =
165.28(18)°] and the near planarity of the same [torsion
angle = −178.52(14)°] including the C-4 phenyl ring. As
suggested by the NMR spectral data, the ethoxy group is not
coplanar to the carbon−carbon double bond, C(3a)−O(3)−
C(3)−C(4) = −118.11(18)°. The torsion angle N(9)−C(2)−
C(1)−O(1) = 99.91(19)° also reveals that the benzoyl moiety
adopts a conformation out of the plane formed by the
conjugated phenylvinyl N-phenylimino system.
Under the same conditions, equimolecular amounts of 1c
and 7a were reacted in 15 mL of CDCl3 as the solvent and
1
monitored by H NMR in order to detect the presence of any
transient species during the course of the cascade reaction.
Aliquots were taken from the reaction mixture every 15 min for
2.0 h. After the first 15 min, it was possible to observe three
groups of signals: a singlet at 6.33 ppm, a quartet at 4.21 ppm,
and a triplet at 1.40 ppm. These signals were attributed to the
H-4 protons, the methylene (CH2), and the methyl (CH3) of
the ethoxy group, respectively, of compound 24i. Additionally,
a quartet at 4.78 ppm and a triplet at 1.60 ppm were assigned to
the ethoxy group of the carbene 1c. As the reaction progressed,
the former signals were found to increase and the latter signals
to decrease. This result suggests that, once formed, the 2,3-
dihydroisoxazole of 1c, as the 1,3-dipolar cycloaddition adduct
of 7a, rapidly reacts to produce the final product 24i.
Figure 2. NOEs observed upon irradiation of protons H-4, H-6, H-15,
and OCH2CH3 for derivative compound 24i.
Therefore, it is likely that the stability of the 2,3-
dihydroisoxazole adduct is strongly altered by the electronic
effect of the carbene group and the N-phenyl substituent
introduced by the C,N-diaryl nitrone 7, promoting conversion
into the rearranged and open-ringed final product 24. This
outcome is partially in agreement with the report by Kalin and
co-workers. They also used a C,N-diaryl nitrone, finding that
the 1,3-dipolar adduct was not isolated, but instead only
products 9a,b, resulting from the rearrangement of the 2,3-
dihydroisoxazole carbenes 8a,b (Scheme 2).8 However, our
results are in contrast to those reported by Chan and co-
workers,9b who were able to isolate the corresponding adducts
13−19 (Scheme 3). Furthermore, derivatives 24 do not have
the structure of enaminones 22 reported by Barluenga and co-
workers, which were produced by oxidation and heterocyclic
ring-opening of the 1,3-dipolar cycloaddition adduct 21
(Scheme 4).10a Indeed, we found no examples in the literature
of the ability to attain this type of compounds (24 and 27)
from a cascade process, starting from the reaction between an
N-phenyl nitrone and an aryl- or a cyclohexenylethynyl carbene
complex. From the structural point of view, the cycloaddends
used in the previous reports8,9b,10a seem to be similar to those
employed in this study. However, the substituents in the
cycloaddends used herein apparently had a significant effect on
the stability of the 1,3-dipolar adducts, promoting the N−O
bond cleavage as the first step in the process of rearrangement.
The lone electron pair of the nitrogen atom in the initially
formed 1,3-dipolar adducts perturbs (raising the energy) the
oxygen lone electron pair, polarizing the N−O bond and
promoting its cleavage, as anticipated by Baldwin.7a The alpha
effect14 could be the origin of this polarization, as a
consequence of the repulsion between the lone electron pairs
of the heteroatoms.7a,15 This polarization can produce an
Figure 3. ORTEP diagram of 24i. Thermal ellipsoids are shown at the
30% probability level. Selected bond distances (Å) and angles (deg):
N(9)−C(2) = 1.275(2), C(2)−C(3) = 1.477(2), C(3)−C(4) =
1.341(2), O(3)−C(3) = 1.3670(18).
and 13C NMR spectra was performed based on the results of
2D experiments (gHSQC and gHMBC). For instance, the
gHMBC spectrum of all products showed long-range two- or
three-bond C−H correlations between the proton H-4 at ∼6.33
ppm and the carbon atoms at ∼129.9 (C-4b), ∼151.6 (C-3),
and ∼164.9 (C-2) ppm, in agreement with the presence of a 4-
phenyl-2-(phenylimino)but-3-en-1-one core.
The (2Z,3Z) configuration of 24i was supported by NOE
experiments, which showed an enhancement of the signals of
protons H-6 and H-15 when H-4 was irradiated and the same
effect in the signal of the latter when protons H-6 and H-15
were irradiated (Figure 2). In addition, there was an observable
enhancement of the signal attributed to proton H-6 upon
irradiation of the methylene in the ethoxy group (Figure 2).
This indicates that the aryl group at C-4 and the ethoxy group
at C-3 are attached to the double carbon−carbon bond in a Z
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electron deficiency at the nitrogen atom, which is largely
stabilized by the presence of the aryl ring, favoring the N−O
bond cleavage.7a,b The stability of this bond could also be
related to the stability of the enolate produced by this cleavage.
In this sense, the strong electron-withdrawing effect of the
carbene moiety could play a significant role in stabilizing the
electron density released by the N−O cleavage (Figure 4).
The reaction sequence seems to be triggered by ring-opening
of the initial and unstable 2,3-dihydroisoxazole carbene
complex 28. This is probably promoted by the strong electron
demand of the carbene moiety conjugated to the endocyclic
double bond, together with the polarization of the N−O
bond,7a which can be explained, as aforementioned, by the
alpha effect.14,16 Although this effect is manifested particularly
in nucleophiles, such as hydrogen peroxide, oximes, and
hydrazines,16e−n it seems likely that the destabilization of the
heteroatom lone pair interaction may also be involved in the
N−O bond polarization of the 4-isoxazoline ring of 28.16n In
addition, according to Baldwin et al.,7a the N−O bond cleavage
is accelerated by the presence of the N-phenyl group that
stabilizes the resulting zwitterionic species,7b which leads to the
formation of the corresponding 2-acylaziridine complex
intermediate 29. As is well known, the aziridine ring moiety
can open to the azomethine ylide complex 30,6a,b,7 in which the
reorganization of the dipole charges is promoted by the
reactivity of the carbon−metal complex to give rise to the
zwitterionic dihydroazete iminocyclobutene pentacarbonylchro-
mium complex intermediate 31.3i,j Decomposition of the latter
yields (3-ethoxy-1,4-dihydroazet-2-yl)(phenyl)methanone
(32), which in turn undergoes a conrotatory ring-opening
that leads to the observed series of stable derivatives 24 and 27
(Scheme 6). It is noteworthy that, in accordance with the
proposed mechanism, the latter compounds would not be
produced if the first 1,3-dipolar cycloaddition were not a highly
regioselective process, with both cycloaddends exclusively
oriented to form the 2,3-dihydroisoxazole carbene complexes
28.17
Figure 4. Polarization proposed for the N−O bond in the 2,3-
dihydroisoxazole adducts.
Thus, the resulting negative charge borne by the oxygen
atom would be stabilized by delocalization onto the carbene
complex conjugated double bond. As a result, the yielded 1,3-
adducts from the N-phenyl nitrones should be more susceptible
to a N−O bond cleavage, leading to the observed rearranged
products.
Although it was not possible to isolate or even obtain
spectroscopic evidence of the 2,3-dihydroisoxazole carbene
complex 28 or the azomethine ylide complex 30, their plausible
ephemeral existence as intermediates could account for the
reaction pathway. A mechanism for this cascade process is
proposed in Scheme 6.
Scheme 6
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Scheme 7
A preliminary reactivity evaluation of these compounds
consisted of treating the isolated 2-(phenylimino)but-3-en-1-
one 24b with 2,4-dinitrophenylhydrazine (2,4-DNPH). For-
mation of a mixture of hydrazones 34/35 was found in good
yield (90%) (Scheme 7). Hydrazone 34 was isolated as orange-
red crystals, and its structure was established by X-ray
diffraction analysis (Figure 5), revealing that the addition of
1a−f with C,N-diaryl nitrones 7a−f, leading to novel and highly
substituted (2Z,3Z)-3-ethoxy-1-(aryl/cyclohexenyl)-4-aryl-2-
(phenylimino)but-3-en-1-one derivatives 24a−k in high regio-
and stereoselectivity. Furthermore, the cascade reactions
between carbene complexes 23a,b and C,N-diaryl nitrones
7a,b and 7d−f successfully proceeded to afford the (2Z,3Z)-3-
ethoxy-1-(cyclohexenyl)-4-aryl-2-(phenylimino)but-3-en-1-
ones 27a−e, corroborating the high regioselectivity found in
the [3 + 2] cycloadditions. This unprecedented transformation
is presumably carried out by a mechanism in which the 2,3-
dihydroisoxazole carbene complexes 28 are formed and
undergo consecutive reactions of rearrangement and ring-
opening, being strongly affected by the electron-withdrawing
effect of the metal−carbene moiety conjugated to the
endocyclic double bond and by the congestion generated by
the vicinal hindered substituted centers in the heterocycle. The
reactivity and synthetic applications of this series of novel
polyfunctionalized molecules 24 and 27 are currently under
study, and the results will be reported in due course.
EXPERIMENTAL SECTION
■
General Procedures and Instrumentation. All reactions were
carried out under nitrogen in anhydrous solvents. Glassware was dried
in an oven prior to use. Commercially available compounds were used
without further purification. Tetrahydrofuran was distilled from
sodium benzophenone ketyl under an N2 atmosphere prior to use.
n-Hexane and ethyl acetate were distilled before use. Melting points
(uncorrected) were determined with a Fisher-Johns melting point
apparatus. 1H NMR and 13C NMR spectra were recorded on a Varian
Mercury (300 MHz) and Varian VNMR System (500 MHz)
instruments, in CDCl3 as solvent and with TMS as internal reference.
High-resolution mass spectra (HRMS) were obtained with a JSM-
GCMate II mass spectrometer, and electron impact techniques (70
eV) were employed. X-ray data were collected on an Oxford
Diffraction Xcalibur S single-crystal X-ray difractometer. Thin-layer
chromatography (TLC) analyses were performed using silica plates
and were visualized using UV (254 nm) or iodine. Flash column
chromatography was performed over Natland International Co. silica
gel (230−400 mesh). C,N-Diaryl nitrones 7a−f and carbene
complexes 1a−f and 23a,b were prepared by the standard methods
previously reported.12,13
General Method for the Tandem [3 + 2] Cycloaddition/
Rearrangement and Ring-Opening Process of the Adducts
24a−k, 27a,b, and 27d,e. Method A. A solution of the
corresponding C,N-diaryl nitrones 7a−e (1.0 molar equiv) in freshly
dried THF (15 mL) was slowly added dropwise via cannula to carbene
complexes of Cr(0) 1a−c and 23a (1.0 molar equiv) at −78 °C under
a nitrogen atmosphere, and then the mixture was allowed to slowly
reach room temperature (∼2−4 h), until the color of the solution
changed from red to green. At this point, the solvent was removed
under vacuum and the residue was dissolved in EtOAc (10 mL) and
filtered over Celite. The solvent was removed under vacuum, and the
crude product was purified by flash column chromatography over silica
Figure 5. ORTEP diagram of 34. Thermal ellipsoids are shown at the
30% probability level. Selected torsion angles (deg): N(9)−C(2)−
C(3)-C(4) = −172.37(11), C(3)−C(4)−C(5)−C(6) = −177.61(12),
C(3a)−O(3)−C(3)−C(4) = −114.65(14), N(9)−C(2)−C(1)−O(1)
= 85.38(16).
the 2,4-DNPH took place at the N-phenylimino group,
maintaining the same (2Z,3Z) configuration of the double
bonds. Moreover, the conjugated phenylvinyl N-phenylimino
system adopts a planar s-trans conformation, leaving the
benzoyl moiety in a nonplanar conformation as well, which is
similar to that found with precursors 24.
CONCLUSIONS
■
We report an unexpected and new [3 + 2] cycloaddition/
rearrangement and ring-opening cascade reaction of the (aryl/
cyclohexenyl)(ethoxy) carbene complexes of Cr(0) and W(0)
G
dx.doi.org/10.1021/om400420c | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
gel using n-hexane/EtOAc (98:2), to afford the corresponding adducts
24a−k, 27a,b, and 27d,e.
MHz, CDCl3) δ 1.39 (t, J = 7.0 Hz, 3H, OCH2CH3), 4.22 (q, J = 7.0
Hz, 2H, OCH2CH3), 6.28 (s, 1H, H-4), 6.81−6.85 (m, 2H, H-11),
6.88−6.92 (m, 1H, H-13), 7.00−7.12 (m, 2H, H-12), 7.27−7.32 (m,
2H, H-7), 7.31−7.37 (m, 2H, H-16), 7.45−7.50 (m, 1H, H-17), 7.66−
7.70 (m, 2H, H-6), 7.75−7.79 (m, 2H, H-15); 13C NMR (125 MHz,
CDCl3) δ 15.6 (OCH2CH3), 68.1 (OCH2CH3), 120.3 (C-11), 124.8
(C-13), 124.9 (C-4), 128.5 (C-7), 128.6 (C-12), 128.8 (C-16), 129.2
(C-15), 131.1 (C-6), 132.5 (C-8), 134.3 (C-17 and C-5), 134.5 (C-
14), 148.7 (C-10), 151.8 (C-3), 164.4 (C-2), 196.6 (C-1); HRMS (EI
+) calcd for C24H20ClNO2 389.1183, found (M+) 389.1190.
General Method for the Tandem [3 + 2] Cycloaddition/
Rearrangement and Ring-Opening Process of the Adducts
24a, 24e−j, and 27a−d. Method B. A solution of the
corresponding C,N-diaryl nitrones 7a−f (1.0 molar equiv) in freshly
dried THF (15 mL) was slowly added dropwise via cannula to carbene
complexes of W(0) 1d−f and 23b (1.0 molar equiv) at −78 °C under
a nitrogen atmosphere, and then the mixture was allowed to slowly
reach room temperature (∼2−4 h), until the color of the solution
changed from red to brown. At this point, the solvent was removed
under vacuum and the residue was dissolved in EtOAc (10 mL) and
filtered over Celite. The solvent was removed under vacuum, and the
crude product was purified by flash column chromatography over silica
gel using n-hexane/EtOAc (98:2) to afford the corresponding adducts
24a, 24e−j, and 27a−d.
(2Z,3Z)-3-Ethoxy-4-(4-nitrophenyl)-1-phenyl-2-
(phenylimino)but-3-en-1-one (24e). According to general method
A, the reaction between 7e (0.690 g, 2.85 mmol) and carbene 1a (1.0
g, 2.85 mmol) afforded 24e (0.503 g, 44%) as a pale orange, viscous
oil. According to general method B, the reaction between 7e (0.10 g,
0.14 mmol) and carbene 1d (0.20 g, 0.414 mmol) afforded 24e (0.069
1
g, 42%): FT-IR (KBr) νmax 1670, 1594, 1341 cm−1; H NMR (500
(2Z,3Z)-3-Ethoxy-1,4-diphenyl-2-(phenylimino)but-3-en-1-
one (24a). According to general method A, the reaction between 7a
(0.562 g, 2.85 mmol) and carbene 1a (1 g, 2.85 mmol) afforded 24a
(0.579 g, 57%) as a yellow solid: mp 53−54 °C. According to general
method B, the reaction between 7a (0.203 g, 1.03 mmol) and carbene
1d (0.500 g, 1.03 mmol) afforded 24e (0.184 g, 50%): FT-IR (KBr)
νmax 1671, 1590, 1271 cm−1; 1H NMR (500 MHz, CDCl3) δ 1.41 (t, J
= 7.0 Hz, 3H, OCH2CH3), 4.21 (q, J = 7.2 Hz, 2H, OCH2CH3), 6.34
(s, 1H, H-4), 6.81−6.85 (m, 2H, H-11), 6.88−6.92 (m, 1H, H-13),
7.10−7.20 (m, 2H, H-12), 7.28−7.30 (m, 1H, H-8), 7.31−7.37 (m,
4H, H-16 and H-7), 7.45−7.50 (m, 1H, H-17), 7.72−7.75 (m, 2H, H-
6), 7.76−7.8 (m, 2H, H-15); 13C NMR (125 MHz, CDCl3) δ 15.6
(OCH2CH3), 67.9 (OCH2CH3), 120.3 (C-11), 124.6 (C-13), 126.4
(C-4), 128.4 (C-8), 128.5 (C-12), 128.7 (C-16 and C-7), 129.1 (C-
15), 129.9 (C-6), 134.0 (C-5), 134.2 (C-17), 134.6 (C-14), 148.9 (C-
10), 151.5 (C-3), 164.8 (C-2), 196.7 (C-1); HRMS (EI+) calcd for
C24H21NO2 355.1572, found (M+) 355.1527.
MHz, CDCl3) δ 1.41 (t, J = 7.2 Hz, 3H, OCH2CH3), 4.30 (q, J = 7.2
Hz, 2H, OCH2CH3), 6.35 (s, 1H, H-4), 6.83−6.87 (m, 2H, H-11),
6.91−6.96 (m, 1H, H-13), 7.10−7.15 (m, 2H, H-12), 7.34−7.39 (m,
2H, H-16), 7.48−7.53 (m, 1H, H-17), 7.75−7.79 (m, 2H, H-15),
7.86−7.90 (m, 2H, H-6), 8.17−8.20 (m, 2H, H-7); 13C NMR (125
MHz, CDCl3) δ 15.6 (OCH2CH3), 68.6 (OCH2CH3), 120.3 (C-11),
122.4 (C-4), 123.6 (C-7), 125.3 (C-13), 127.9 (C-12), 128.6 (C-16),
128.7 (C-15), 130.2 (C-6), 134.2 (C-14), 134.5 (C-17), 140.6 (C-5),
146.9 (C-8), 148.3 (C-10), 154.3 (C-3), 163.8 (C-2), 196.3 (C-1);
HRMS (EI+) calcd for C24H20N2O4 400.1423, found (M+) 400.1475.
(2Z,3Z)-3-Ethoxy-4-(4-methoxyphenyl)-1-(4-methylphenyl)-
2-(phenylimino)but-3-en-1-one (24f). According to general
method A, the reaction between 7b (0.270 g, 1.37 mmol) and
carbene 1b (0.500 g, 1.37 mmol) afforded 24f (0.304 g, 60%) as a
bright yellow solid: mp 90−91 °C. According to general method B, the
reaction between 7b (0.091 g, 0.403 mmol) and carbene 1e (0.20 g,
0.403 mmol) afforded 24f (0.085 g, 53%): FT-IR (KBr) νmax 1668,
1603, 1254 cm−1; 1H NMR (500 MHz, CDCl3) δ 1.42 (t, J = 7.2 Hz,
3H, OCH2CH3), 2.31 (s, 3H, CH3), 3.79 (s, 3H, OCH3), 4.21 (q, J =
7.2 Hz, 2H, OCH2CH3), 6.26 (s, 1H, H-4), 6.83−6.88 (m, 4H, H-7
and H-11), 6.90−6.91 (m, 1H, H-13), 7.07−7.14 (m, 4H, H-12 and
H-16), 7.68−7.72 (m, 4H, H-6 and H-15); 13C NMR (125 MHz,
CDCl3) δ 15.6 (OCH2CH3), 21.7 (CH3), 55.2 (OCH3), 67.6
(OCH2CH3), 113.8 (C-7), 120.4 (C-11), 124.4 (C-13), 126.8 (C-4),
126.8 (C-5), 128.4 (C-12), 129.4 (C-16), 129.5 (C-15), 131.6 (C-6),
132.2 (C-14), 145.4 (C-17), 149.1 (C-10), 150.0 (C-3), 159.9 (C-8),
164.9 (C-2), 196.4 (C-1); HRMS (EI+) calcd for C26H25O3N
399.1834, found (M+) 399.1833.
(2Z,3Z)-4-(4-Chlorophenyl)-3-ethoxy-1-(4-methylphenyl)-2-
(phenylimino)but-3-en-1-one (24g). According to general method
A, the reaction between 7d (0.092 g, 0.39 mmol) and carbene 1b (0.14
g, 0.39 mmol) afforded 24g (0.075 g, 47%) as a bright yellow, viscous
oil. According to general method B, the reaction between 7d (0.231 g,
1.0 mmol) and carbene 1e (0.50 g, 1.0 mmol) afforded 24g (0.182 g,
45%): FT-IR (KBr) νmax 1667, 1604, 1281 cm−1; 1H NMR (500 MHz,
CDCl3) δ 1.39 (t, J = 7.0 Hz, 3H, OCH2CH3), 2.31 (s, 3H, CH3), 4.22
(q, J = 7.0 Hz, 2H, OCH2CH3), 6.26 (s, 1H, H-4), 6.83−6.87 (m, 2H,
H-11), 6.88−6.93 (m, 1H, H-13), 7.00−7.11 (m, 2H, H-12), 7.12−
7.15 (m, 2H, H-7), 7.26−7.30 (m, 2H, H-16), 7.65−7.70 (m, 4H, H-6
and H-15); 13C NMR (125 MHz, CDCl3) δ 15.5 (OCH2CH3), 21.7
(CH3), 68.0 (OCH2CH3), 120.3 (C-11), 124.6 (C-4), 124.7 (C-13),
128.5 (C-7), 128.6 (C-16), 129.3 (C-12), 129.5 (C-15), 131.0 (C-6),
132.0 (C-14), 132.5 (C-5), 134.2 (C-8), 145.5 (C-17), 148.8 (C-10),
151.9 (C-3), 164.5 (C-2), 196.0 (C-1); HRMS (EI+) calcd for
C25H22ClO2N 403.1339, found (M+) 403.1345.
(2Z,3Z)-3-Ethoxy-4-(4-methoxyphenyl)-1-phenyl-2-
(phenylimino)but-3-en-1-one (24b). According to general method
A, the reaction between 7b (0.322 g, 1.41 mmol) and carbene 1a
(0.500 g, 1.42 mmol) afforded 24b (0.385 g, 70%) as a yellow solid:
1
mp 97−98 °C; FT-IR (KBr) νmax 1671, 1583, 1254 cm−1; H NMR
(500 MHz, CDCl3) δ 1.42 (t, J = 7.0 Hz, 3H, OCH2CH3), 3.81 (s, 3H,
OCH3), 4.21 (q, J = 7.0 Hz, 2H, OCH2CH3), 6.28 (s, 1H, H-4), 6.80−
6.83 (m, 2H, H-11), 6.84−6.88 (m, 2H, H-7), 6.89−6.90 (m, 1H, H-
13), 7.00−7.10 (m, 2H, H-12), 7.32−7.36 (m, 2H, H-16), 7.44−7.49
(m, 1H, H-17), 7.60−7.73 (m, 2H, H-6), 7.77−7.79 (m, 2H, H-15);
13C NMR (125 MHz, CDCl3) δ 15.6 (OCH2CH3), 55.2 (OCH3), 67.6
(OCH2CH3), 113.9 (C-7), 120.4 (C-11), 124.4 (C-13), 126.7 (C-4),
126.8 (C-14), 128.4 (C-12), 128.7 (C-16), 129.2 (C-15), 131.6 (C-6),
134.1 (C-17), 134.7 (C-5), 149.0 (C-10), 149.9 (C-3), 159.9 (C-8),
164.8 (C-2), 196.9 (C-1); HRMS (EI+) calcd for C25H23O3N
385.1678, found (M+) 385.1678.
(2Z,3Z)-3-Ethoxy-1-phenyl-2-(phenylimino)4-(3,4,5-
trimethoxyphenyl)but-3-en-1-one (24c). According to general
method A, the reaction between 7c (0.818 g, 2.85 mmol) and carbene
1a (1.0 g, 2.85 mmol) afforded 24c (0.957 g, 75%) as a bright yellow,
1
viscous oil: FT-IR (KBr) νmax 1663, 1597, 1258 cm−1; H NMR (500
MHz, CDCl3) δ 1.45 (t, J = 7.2 Hz, 3H, OCH2CH3), 3.84 (s, 6H,
2OCH3), 3.86 (s, 3H, OCH3), 4.24 (q, J = 7.2 Hz, 2H, OCH2CH3),
6.24 (s, 1H, H-4), 6.82−6.84 (m, 2H, H-11), 6.88−6.91 (m, 1H, H-
13), 7.00−7.12 (m, 4H, H-6 and H-12), 7.32−7.36 (m, 2H, H-16),
7.45−7.50 (m, 1H, H-17), 7.76−7.80 (m, 2H, H-15); 13C NMR (125
MHz, CDCl3) δ 15.8 (OCH2CH3), 56.0 (2OCH3), 60.8 (OCH3), 67.9
(OCH2CH3), 107.2 (C-6), 120.3 (C-11), 124.6 (C-13), 126.6 (C-4),
128.5 (C-12), 128.7 (C-16), 129.2 (C-15), 129.4 (C-8), 134.3 (C-17),
134.6 (C-14), 138.7 (C-5), 148.8 (C-10), 151.0 (C-3), 152.9 (C-7),
164.5 (C-2), 196.8 (C-1); HRMS (EI+) calcd for C27H27O5N
445.1889, found (M+) 445.1871.
(2Z,3Z)-3-Ethoxy-4-(4-nitrophenyl)-1-(4-methylphenyl)-2-
(phenylimino)but-3-en-1-one (24h). According to general method
A, the reaction between 7e (0.198 g, 0.82 mol) and carbene 1b (0.30
g, 0.82 mmol) afforded 24h (0.136 g, 40%) as an orange solid: mp
(2Z,3Z)-4-(4-Chlorophenyl)-3-ethoxy-1-phenyl-2-
(phenylimino)but-3-en-1-one (24d). According to general method
A, the reaction between 7d (0.165 g, 0.714 mmol) and carbene 1a
(0.250 g, 0.714 mmol) afforded 24d (0.152 g, 55%) as an orange,
1
100−101 °C; FT-IR (KBr) νmax 1665, 1515, 1340 cm−1; H NMR
(500 MHz, CDCl3) δ 1.41 (t, J = 7.0 Hz, 3H, OCH2CH3), 2.33 (s, 3H,
CH3), 4.30 (q, J = 7.0 Hz, 2H, OCH2CH3), 6.33 (s, 1H, H-4), 6.86−
6.88 (m, 2H, H-11), 6.94−6.96 (m, 1H, H-13), 7.12−7.17 (m, 4H, H-
1
viscous oil: FT-IR (KBr) νmax 1671, 1584, 1089 cm−1; H NMR (500
H
dx.doi.org/10.1021/om400420c | Organometallics XXXX, XXX, XXX−XXX

Organometallics
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12 and H-16), 7.67−769 (m, 2H, H-15), 7.86−7.89 (m, 2H, H-6),
8.10−8.20 (m, 2H, H-7); 13C NMR (125 MHz, CDCl3) δ 15.5
(OCH2CH3), 21.8 (CH3), 68.6 (OCH2CH3), 120.3 (C-11), 122.3 (C-
4), 123.6 (C-7), 125.2 (C-13), 128.6 (C-16), 129.4 (C-15), 129.7 (C-
12), 130.2 (C-6), 131.8 (C-14), 140.6 (C-5), 145.9 (C-17), 146.9 (C-
8), 148.4 (C-10), 154.4 (C-3), 163.9 (C-2), 195.7 (C-1); HRMS (EI
+) calcd for C25H22N2O4 414.1580, found (M+) 414.1555.
NMR (125 MHz, CDCl3) δ 15.6 (OCH2CH3), 21.3 (C-17), 21.3 (C-
18), 21.8 (C-19), 26.2 (C-16), 67.8 (OCH2CH3), 120.1 (C-11), 124.3
(C-13), 126.0 (C-4), 128.4 (C-12), 128.5 (C-7), 128.6 (C-8), 129.9
(C-6), 134.2 (C-5), 138.5 (C-14), 147.6 (C-15), 149.9 (C-10), 151.8
(C-3), 165.5 (C-2), 197.7 (C-1); HRMS (EI+) calcd for C24H25NO2
359.1885, found (M+) 359.1913.
(2Z,3Z)-1-Cyclohexenyl-3-ethoxy-4-(4-methoxyphenyl)-2-
(phenylimino)but-3-en-1-one (27b). According to general method
A, the reaction between 7b (0.320 g, 1.41 mmol) and carbene 23a
(0.500 g, 1.41 mmol) afforded 27b (0.291 g, 53%) as a bright yellow,
viscous oil. According to general method B, the reaction between 7b
(0.140 g, 0.617 mmol) and carbene 23b (0.300 g, 0.617 mmol)
afforded 27b (0.108 g, 45%): FT-IR (KBr) νmax 1655, 1584, 1253
cm−1; 1H NMR (500 MHz, CDCl3) δ 1.36−1.41 (m, 7H, OCH2CH3,
H-17 and H-18), 1.54−1.80 (m, 2H, H-19), 1.90−2.03 (m, 2H, H-16),
3.81 (s, 3H, OCH3), 4.17−4.22 (m, 2H, OCH2CH3), 6.26 (s, 1H, H-
4), 6.73−6.74 (m, 1H, H-15), 6.77−6.78 (m, 2H, H-11), 6.87−6.90
(m, 2H, H-7), 6.98−7.02 (m, 1H, H-13), 7.19−7.22 (m, 2H, H-12),
7.74−7.77 (m, 2H, H-6); 13C NMR (125 MHz, CDCl3) δ 15.5
(OCH2CH3), 21.2 (C-17), 21.3 (C-18), 21.7 (C-19), 26.0 (C-16),
55.1 (OCH3), 67.3 (OCH2CH3), 113.7 (C-7), 120.0 (C-11), 124.0
(C-13), 126.1 (C-4), 126.9 (C-5), 128.3 (C-12), 131.4 (C-6), 138.4
(C-14), 147.3 (C-15), 149.9 (C-10), 150.1 (C-3), 159.7 (C-8), 165.5
(C-2), 197.7 (C-1); HRMS (EI+) calcd for C25H27NO3 389.1991,
found (M+) 389.1988.
(2Z,3Z)-3-Ethoxy-1-(4-methoxyphenyl)-4-phenyl-2-
(phenylimino)but-3-en-1-one (24i). According to general method
A, the reaction between 7a (0.155 g, 0.78 mmol) and carbene 1c
(0.300 g, 0.78 mmol) afforded 24i (0.167 g, 55%) as a bright yellow
solid: mp 98−99 °C. According to general method B, the reaction
between 7a (0.192 g, 0.97 mmol) and carbene 1f (0.500 g, 0.97 mmol)
afforded 24i (0.207 g, 55%): FT-IR (KBr) νmax 1660, 1595, 1262
cm−1; 1H NMR (500 MHz, CDCl3) δ 1.41 (t, J = 7.2 Hz, 3H,
OCH2CH3), 3.79 (s, 3H, OCH3), 4.21 (q, J = 7.2 Hz, 2H,
OCH2CH3), 6.33 (s, 1H, H-4), 6.70−683 (m, 2H, H-16), 6.84−6.87
(m, 2H, H-11), 6.89−6.92 (m, 1H, H-13), 7.10−7.13 (m, 2H, H-12),
7.25−7.29 (m, 1H, H-8), 7.31−7.34 (m, 2H, H-7), 7.73−7.74 (m, 2H,
H-6), 7.75−7.78 (m, 2H, H-15); 13C NMR (125 MHz, CDCl3) δ 15.5
(OCH2CH3), 55.4 (OCH3), 67.9 (OCH2CH3), 114.0 (C-16), 120.3
(C-11), 124.5 (C-13), 126.4 (C-4), 127.7 (C-5), 128.3 (C-12), 128.4
(C-7), 128.6 (C-8), 129.9 (C-6), 131.7 (C-15), 134.1 (C-14), 149.0
(C-10), 151.6 (C-3), 164.3 (C-17), 164.9 (C-2), 194.8 (C-1); HRMS
(EI+) calcd for C25H23NO3 385.1678, found (M+) 385.1695.
(2Z,3Z)-3-Ethoxy-1, 4-bis(4-methoxyphenyl)-2-
(phenylimino)but-3-en-1-one (24j). According to general method
A, the reaction between 7b (0.417 g, 1.84 mmol) and carbene 1c (0.70
g, 1.84 mmol) afforded 24j (0.344 g, 45%) as a bright yellow solid: mp
70−71 °C. According to general method B, the reaction between 7b
(0.155 g, 0.68 mmol) and carbene 1f (0.350 g, 0.68 mmol) afforded
(2Z,3Z)-4-(4-Chlorophenyl)-1-cyclohexenyl-3-ethoxy-2-
(phenylimino)but-3-en-1-one (27c). According to general method
B, the reaction between 7d (0.100 g, 0.43 mmol) and carbene 23b
(0.210 g, 0.43 mmol) afforded 27c (0.063 g, 37%) as a red solid: mp
1
40−41 °C; FT-IR (KBr) νmax 1656, 1586, 1382 cm−1; H NMR (300
MHz, CDCl3) δ 1.36−1.41 (m, 7H, OCH2CH3, H-17 and H-18),
1.60−1.80 (m, 2H, H-19), 2.00−2.15 (m, 2H, H-16), 4.10−4.20 (m,
2H, OCH2CH3), 6.23 (s, 1H, H-4), 6.70−6.73 (m, 1H, H-15), 6.77−
6.80 (m, 2H, H-11), 7.01−7.06 (m, 1H, H-13), 7.20−7.26 (m, 2H, H-
12), 7.31−7.35 (m, 2H, H-7), 7.71−7.75 (m, 2H, H-6); 13C NMR (75
MHz, CDCl3) δ 15.6 (OCH2CH3), 21.2 (C-17), 21.3 (C-18), 21.7 (C-
19), 26.2 (C-16), 67.9 (OCH2CH3), 120.0 (C-11), 124.5 (C-4), 124.5
(C-13), 128.5 (C-12), 128.6 (C-7), 130.0 (C-6), 132.6 (C-5), 134.1
(C-8), 138.4 (C-14), 147.9 (C-15), 149.7 (C-10), 152.1 (C-3), 165.1
(C-2), 197.6 (C-1); HRMS (EI+) calcd for C24H24ClNO2 393.1496,
found (M+) 393.1491.
(2Z,3Z)-1-Cyclohexenyl-3-ethoxy-4-(4-nitrophenyl)-2-
(phenylimino)but-3-en-1-one (27d). According to general method
A, the reaction between 7e (0.341 g, 1.41 mmol) and carbene 23a
(0.50 g, 1.41 mmol) afforded 27d (0.228 g, 40%) as a red solid: mp
41−42 °C. According to general method B, the reaction between 7e
(0.247 g, 1.02 mmol) and carbene 23b (0.500 g, 0.1.02 mmol)
afforded 27b (0.166 g, 40%); FT-IR (KBr) νmax 1598, 1520, 1343
cm−1; 1H NMR (500 MHz, CDCl3) δ 1.39−1.42 (m, 7H, OCH2CH3,
H-17 and H-18), 1.60−1.79 (m, 2H, H-19), 2.10−2.17 (m, 2H, H-16),
4.25 (q, J = 7.0 Hz, 2H, OCH2CH3), 6.31 (s, 1H, H-4), 6.70−6.73 (m,
1H, H-15), 6.77−6.80 (m, 2H, H-11), 7.05−7.09 (m, 1H, H-13),
7.22−7.28 (m, 2H, H-12), 7.91−7.95 (m, 2H, H-6), 8.18−8.22 (m,
2H, H-7); 13C NMR (125 MHz, CDCl3) δ 15.6 (OCH2CH3), 21.2
(C-17), 21.3 (C-18), 21.8 (C-19), 26.2 (C-16), 68.4 (OCH2CH3),
119.9 (C-11), 121.9 (C-4), 123.6 (C-7), 124.9 (C-13), 128.6 (C-12),
130.1 (C-6), 138.3 (C-14), 140.7 (C-5), 146.7 (C-8), 148.0 (C-15),
149.3 (C-10), 154.6 (C-3), 164.5 (C-2), 197.1 (C-1); HRMS (EI+)
calcd for C24H24N2O4 404.1736, found (M+) 404.2063.
1
24j (0.113 g, 40%): FT-IR (KBr) νmax 1663, 1597, 1258 cm−1; H
NMR (500 MHz, CDCl3) δ 1.42 (t, J = 7.0 Hz, 3H, OCH2CH3), 3.77
(s, 3H, OCH3), 3.79 (s, 3H, OCH3), 4.21 (q, J = 7.0 Hz, 2H,
OCH2CH3), 6.28 (s, 1H, H-4), 6.77−6.80 (m, 2H, H-7), 6.84−6.87
(m, 4H, H-11 and H-16), 6.87−6.89 (m, 1H, H-13), 7.00−7.11 (m,
2H, H-12), 7.68−7.72 (m, 2H, H-6), 7.75−7.77 (m 2H, H-15); 13C
NMR (125 MHz, CDCl3) δ 15.5 (OCH2CH3), 55.0 (OCH3), 55.3
(OCH3), 67.4 (OCH2CH3), 113.7 (C-16), 113.9 (C-7), 120.2 (C-11),
124.2 (C-13), 126.5 (C-4), 126.7 (C-5), 127.7 (C-14), 128.3 (C-12),
131.5 (C-6), 131.8 (C-15), 149.1 (C-10), 149.9 (C-3), 159.8 (C-8),
164.2 (C-17), 164.8 (C-2), 194.8 (C-1); HRMS (EI+) calcd for
C26H25NO4 415.1784, found (M+) 415.1989.
(2Z,3Z)-3-Ethoxy-4-(4-nitrophenyl)-1-(4-methoxyphenyl)-2-
(phenylimino)but-3-en-1-one (24k). According to general method
A, the reaction between 7e (0.317 g, 1.31 mmol) and carbene 1c
(0.500 g, 1.31 mmol) afforded 24k (0.226 g, 40%) as an orange,
1
viscous oil: FT-IR (KBr) νmax 1660, 1595, 1263 cm−1; H NMR (500
MHz, CDCl3) δ 1.42 (t, J = 7.0 Hz, 3H, OCH2CH3), 3.81 (s, 3H,
OCH3), 4.30 (q, J = 7.0 Hz, 2H, OCH2CH3), 6.33 (s, 1H, H-4), 6.82−
6.85 (m, 2H, H-16), 6.86−6.90 (m, 2H, H-11), 6.93−6.97 (m, 1H, H-
13), 7.12−7.17 (m, 2H, H-12), 7.74−7.77 (m, 2H, H-15), 7.86−7.89
(m, 2H, H-6), 8.15−8.19 (m, 2H, H-7); 13C NMR (125 MHz, CDCl3)
δ 15.6 (OCH2CH3), 55.4 (OCH3), 68.5 (OCH2CH3), 114.2 (C-16),
120.2 (C-11), 122.4 (C-4), 123.5 (C-7), 125.1 (C-13), 127.3 (C-14),
128.6 (C-12), 130.2 (C-6), 131.7 (C-15), 141.2 (C-5), 147.1 (C-8),
148.0 (C-10), 154.2 (C-3), 163.9 (C-2), 164.8 (C-17), 194.3 (C-1);
HRMS (EI+) calcd for C25H22N2O5 430.1529, found (M+) 430.1649.
(2Z,3Z)-1-Cyclohexenyl-3-ethoxy-4-phenyl-2-(phenylimino)-
but-3-en-1-one (27a). According to general method A, the reaction
between 7a (0.220 g, 1.12 mmol) and carbene 23a (0.400 g, 1.12
mmol) afforded 27a (0.182 g, 45%) as a red, viscous oil. According to
general method B, the reaction between 7a (0.121 g, 0.617 mmol) and
carbene 23b (0.300 g, 0.617 mmol) afforded 27a (0.077 g, 35%); FT-
IR (KBr) νmax 1656, 1596, 1224 cm−1; 1H NMR (500 MHz, CDCl3) δ
1.37−1.42 (m, 7H, OCH2CH3, H-17 and H-18), 1.58−1.73 (m, 2H,
H-19), 2.04−2.25 (m, 2H, H-16), 4.12−4.20 (m, 2H, OCH2CH3),
6.30 (s, 1H, H-4), 6.72−6.75 (m, 1H, H-15), 6.76−6.79 (m, 2H, H-
11), 7.01−7.04 (m, 1H, H-13), 7.20−7.24 (m, 2H, H-12), 7.27−731
(m, 1H, H-8), 7.34−7.37 (m, 2H, H-7), 7.77−7.80 (m, 2H, H-6); 13C
(2Z,3Z)-1-Cyclohexenyl-3-ethoxy-4-(3-nitrophenyl)-2-
(phenylimino)but-3-en-1-one (27e). According to general method
A, the reaction between 7f (0.34 g, 1.41 mmol) and carbene 23a (0.50
g, 1.41 mmol) afforded 27e (0.21 g, 36%) as an orange, viscous oil;
FT-IR (KBr) νmax 1575, 1529, 1350 cm−1; 1H NMR (500 MHz,
CDCl3) δ 1.42−1.46 (m, 7H, OCH2CH3, H-19 and H-20), 1.60−1.80
(m, 2H, H-21), 2.10−2.17 (m, 2H, H-18), 4.20−4.26 (m, 2H,
OCH2CH3), 6.30 (s, 1H, H-4), 6.71−6.73 (m, 1H, H-17), 6.77−6.80
(m, 2H, H-13), 7.05−7.09 (m, 1H, H-15), 7.22−7.28 (m, 2H, H-14),
7.51−7.54 (m, 1H, H-9), 8.03−8.05 (m, 1H, H-10), 8.12−8.14 (m,
1H, H-8), 875−8.76 (m, 1H, H-6); 13C NMR (125 MHz, CDCl3) δ
I
dx.doi.org/10.1021/om400420c | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
15.6 (OCH2CH3), 21.2 (C-19), 21.3 (C-20), 21.8 (C-21), 26.2 (C-
18), 68.3 (OCH2CH3), 119.9 (C-13), 121.3 (C-4), 122.7 (C-8), 124.2
(C-6), 124.8 (C-15), 128.6 (C-14), 129.2 (C-9), 135.3 (C-10), 135.8
(C-16), 138.3 (C-5), 148.2 (C-7), 148.2 (C-17), 149.4 (C-12), 153.7
(C-3), 164.5 (C-2), 197.3 (C-1); HRMS (EI+) calcd for C24H24N2O4
404.1736, found (M+) 404.1728.
graphic information for 24i and 34 in cif format, including X-
ray diffraction data, atomic coordinates, thermal parameters,
and complete bond distances and angles. This material is
available free of charge via the Internet at http://pubs.acs.org
and from the Cambridge Crystallographic Data Centre (fax:
+44-1223-336-003; e-mail: deposit@ccdc.cam.ac.uk; or http//
www.ccdc.cam.ac.uk) as supplementary publication nos. CCDC
936758 (24i) and CCDC 936889 (34).
Derivatization of Compound 24b. A solution of 2,4-
dinitrophenylhydrazine (1.03 mmol, 0.203 g) in 5 mL of ethanol
was cautiously added to 24b (1.03 mmol, 0.40 g) at room temperature
(4 h), until the formation of a red solid. At this point, the solvent was
removed under vacuum, and the crude product was purified by column
chromatography over silica gel using n-hexane/EtOAc (80:20),
affording the derivative products as orange-red solids: 34 (30%, 8.34
mg, mp 155−156 °C) and 35 (38%, 0.142 mg, mp 152−153 °C).
(2Z,3Z)-3-Ethoxy-2-[2-(2,4-dinitrophenyl)hydrazono]-4-(4-
methoxyphenyl)-1-phenylbut-3-en-1-one (34). FT-IR (KBr)
AUTHOR INFORMATION
Notes
The authors declare no competing financial interest.
■
ACKNOWLEDGMENTS
■
1
νmax 3263, 1665, 1595, 1335 cm−1; H NMR (500 MHz, CDCl3) δ
We thank Bruce Allan Larsen for revising the English of the
manuscript. F.D. acknowledges CONACYT (Grant 156933)
and SIP-IPN (Grants 20121096 and 20130913) for financial
support. J.T. acknowledges CONACYT (Grant 83446) and
SIP-IPN (Grants 20120830 and 20130686) for financial
support. M.I.F-C. thanks CONACYT for a graduate scholarship
(No. 206928). F.D. and J.T. are fellows of the EDI-IPN and
COFAA-IPN programs.
1.48 (t, J = 7.0 Hz, 3H, OCH2CH3), 3.83 (s, 3H, OCH3), 4.27 (q, J =
7.0 Hz, 2H, OCH2CH3), 6.82 (s, 1H, H-4), 6.87−6.89 (m, 2H, H-7),
726−748 (m, 3H, H-18 and H-20), 7.74−7.79 (m, 4H, H-6 and H-
19), 8.18−8.20 (m, 1H, H-16), 8.39−8.42 (m, 1H, H-15), 9.12−9.13
(m, 1H, H-13), 11.76 (sa, 1H, N−H); 13C NMR (125 MHz, CDCl3) δ
15.8 (OCH2CH3), 55.4 (OCH3), 68.2 (OCH2CH3), 114.3 (C-7),
116.5 (C-16), 123.3 (C-13), 125.3 (C-5), 126.9 (C-19), 129.0 (C-18),
130.0 (C-15), 130.4 (C-12), 130.8 (C-20), 133.1 (C-6), 133.6 (C-17),
134.0 (C-4), 138.9 (C-14), 144.7 (C-11), 149.9 (C-3), 152.5 (C-2),
161.8 (C-8), 191.7 (C-1); EM HRMS (EI+) calcd for C25H22N4O7
490.1488, found (M+) 490.1531.
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Figures giving H and 13C NMR data for 24a−k, 27a−e, 34,
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dx.doi.org/10.1021/om400420c | Organometallics XXXX, XXX, XXX−XXX

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(17) The mechanism has also been supported by preliminary
B3LYP/(LANL2TZ+f,6-311+G**)//B3LYP/(LANL2DZ,6-31G**)
calculations. Thermodynamic calculations show that the single steps
and the whole process are spontaneous. The single steps include 7 to
28 (ΔG° = −19.8 kcal/mol), 28 to 29 (ΔG° = −13.8 kcal/mol), 29 to
K
dx.doi.org/10.1021/om400420c | Organometallics XXXX, XXX, XXX−XXX