Synthesis and Diels - Alder cycloadditions of exo-imidazolidin-2-one dienes

Article abstract of DOI:10.1021/jo201335y

(Figure presented) An efficient and versatile synthesis of novel exo-imidazolidin-2-one dienes is described. This involves the base-assisted condensation/cyclization cascade reaction of the monoimino derivatives of diacetyl with a series of isocyanates. This methodology enables preparation of symmetrical dienes, as long as the substrates have the same N substituent. Moreover, use of different N-substituted starting materials leads to formation of nonsymmetrical dienes. The reactivity of these dienes was evaluated in Diels - Alder reactions, showing a high reactivity.

Full text of DOI:10.1021/jo201335y

ARTICLE
pubs.acs.org/joc
Synthesis and DielsꢀAlder Cycloadditions of exo-Imidazolidin-
2-one Dienes
Rafael Bautista,† Pablo Bernal,†,‡ Rafael Herrera,§ Blanca M. Santoyo,† J. Miguel Lazcano-Seres,‡
Francisco Delgado,† and Joaquín Tamariz*,†
†Departamento de Química Orgꢀanica, Escuela Nacional de Ciencias Biolꢀogicas, Instituto Politꢀecnico Nacional, Prol.
Carpio y Plan de Ayala, S/N, 11340 Mꢀexico, D. F. Mexico
‡Departamento de Investigaciꢀon y Desarrollo, Signa, S.A. de C.V., Av. Industria Automotriz No. 301, Zona Industrial Toluca,
50200, Toluca, Estado de Mꢀexico, Mexico
§Instituto de Investigaciones Quimicobiolꢀogicas, Universidad Michoacana de San Nicolas de Hidalgo, Edif. B-1,
Ciudad Universitaria, Francisco J. Mujica S/N, 58066 Morelia, Michoacꢀan, Mexico
S Supporting Information
b
ABSTRACT:
An efficient and versatile synthesis of novel exo-imidazolidin-2-one dienes is described. This involves the base-assisted
condensation/cyclization cascade reaction of the monoimino derivatives of diacetyl with a series of isocyanates. This methodology
enables preparation of symmetrical dienes, as long as the substrates have the same N substituent. Moreover, use of different
N-substituted starting materials leads to formation of nonsymmetrical dienes. The reactivity of these dienes was evaluated in
DielsꢀAlder reactions, showing a high reactivity.
Scheme 1. Synthesis of exo-2-Oxazolidinone Dienes and
’ INTRODUCTION
Their Conversion into Carbazoles
Conjugated dienes represent a privileged molecular system for
evaluating the stereospecificity, endo/exo stereoselectivity, regios-
electivity, and π-facial control, among other properties, in
DielsꢀAlder cycloaddition.1 Owing to the seminal importance
of this process from a theoretical point of view,2 as well as to its
potential in synthesis,3 a diversity of dienes have been designed,
including outer-ring o-carbodimethylenes.4 In particular, there has
been considerable interest in the preparation and study of the
reactivity of exo-heterocyclic dienes,4c,5 because the heteroatoms
enhance their reactivity in DielsꢀAlder reactions, and by this
means, heteroatomic substituents can be readily and selectively
introduced to the cyclohexene frame.
Previously, we described the regio- and stereoselective synthesis
of novel N-substituted exo-2-oxazolidinone dienes 1ꢀ36 through a
cascade reaction that involves a base-assisted condensation of α-
diketones 4 and isocyanates 5 in the presence of a dehydrating
agent (Scheme 1). This methodology was successfully applied to
the synthesis of 1,4-disubstituted dienes7 and heterocycle-fused
endo-cyclohexenic dienes.8 These dienes proved to be highly
regioselective in DielsꢀAlder additions to monosubstituted die-
nophiles with electron-withdrawing groups,6 whose correspond-
ing adducts were useful templates for preparing 2-(3H)-
benzoxazolones 69 and for developing a general approach for
preparation of the carbazole scaffold 7.10 This approach was
applied in the total synthesis of natural carbazoles.11 Moreover,
dienes 1ꢀ3 have also been efficient substrates for the synthesis of
η4:π2-diene iridium(I) complexes, which react with alkynylpho-
sphines and aldehydes to yield rearranged η2:σ2-iridium(III)
complexes,12 and for the synthesis of Fe(CO)3 complexes and
to study their reactivity toward alkyllithium addition reactions for
preparation of conjugated enamidoꢀenol Fe(CO)3 complexes.13
These dienes were also converted into new polycyclic oxazol-2-
Received: June 25, 2011
Published: August 15, 2011
r
2011 American Chemical Society
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Scheme 2. exo-Imidazolidin-2-one Dienes as Precursors of
Benzimidazol-2-ones
Scheme 3. Synthesis of exo-Imidazolidin-2-one Dienes from
Ureas
one derivatives by a cascade [4 + 2] cycloaddition/cyclopentan-
nulation/1,5-sigmatropic rearrangement process with Fischer
(arylalkynyl)(alkoxy)carbenes.14
Table 1. Yields of Dienes 8aꢀ8d, Obtained by Condensation
NMR Data for Selected Nucleib
of α-Diacetyl (4a) and Isocyanates 5aꢀd,a and 1H and 13
C
Owingtothe relevance of theexo-heterocyclicdienes and to our
ongoing studies toward preparation of new heterocyclic systems
and with the aim of determining the scope of the cascade reaction
applied in the preparation of dienes 1ꢀ3, the synthesis of novel
exo-imidazolidin-2-one dienes 8 and 9 was undertaken and the
results are herein disclosed. In principle, they could be valuable
synthons in the preparation of vicinal diamino compounds15 and
ofpharmacologicallyactive benzimidazol-2-ones10(Scheme 2).16
’ RESULTS AND DISCUSSION
δ
δ
δ
δ
δ
entry
5 (Ar)
5a (C6H5)
8 (%)c (Ha) (Hb) (C-2) (C-4)d (C-6)e
The first attempt to synthesize dienes 8 was designed on the
basis of two approaches: (a) the mechanism of formation of
dienes 16ꢀ8 and (b) the simple concept of disconnection, i.e., that
the heterocycle may be built through a condensation reaction
between diacetyl (4a) and N,N-diphenylurea (11a) (Scheme 3).
Actually, preliminary results for the synthesis of diene 1a, using a
not strictly dry solvent (dioxane), showed variable yields of diene
8a, presumably by hydrolysis of the isocyanate to give the
respective urea. Consequently, a series of ureas were submitted
to react with 4a. However, for most of cases, the desired dienes 8
were either not detected in the crude mixtures or they were
isolated in very low yield (<15%).
1
2
3
4
8a (25) 4.37 4.82 153.5 140.0 82.9
5b (C6H4-4-Me) 8b (35) 4.30 4.78 153.7 140.3 82.6
5c (C6H4-4-OMe) 8c (36) 4.26 4.77 154.0 140.6 82.6
5d (C6H4-3-Cl)
8d (50) 4.41 4.87 152.8 139.3 83.8
a Reaction conditions: 5 (2.5 mol equiv), Et3N (2.5 mol equiv), Li2CO3
(10 mol equiv), and toluene (30 mL) at 20 °C for 24 h. b In CDCl3 as the
solvent and TMS as the internal standard. c After column chromatography
and recrystallization. d By molecularsymmetry, this value also corresponds
to C-5. e By molecular symmetry, this value also corresponds to C-7.
Although these preliminary results were unsuccessful, we were
able to standardize a method of synthesis of dienes 8 by
condensing diacetyl (4a) with isocyanates 5aꢀd. Thus, upon
applying similar conditions (Et3N, Li2CO3, 20 °C, 24 h) to the
preparation of dienes 1 (Scheme 1), though without drying
solvent and reagents, and by using toluene as the solvent, a series
of dienes 8aꢀd was obtained in low to moderate yields as stable
powders (Table 1). The structure of these novel compounds was
was irradiated, an enhancement was found in both signals of the
doublet attributed to the in protons H-6b/H-7b as well as in the
signals of the multiplet attributed to the aromatic protons.
Since dienes 8aꢀd could not be obtained by condensation of
ureas 11 with 4a, the method described in Table 1 would rule out
the idea of in situ formation of ureas as reaction intermediates.
Therefore, it was considered that in situ formation of other
reactive species, such as bis-imines 13, enamines 14, and/or
monoimines 15, possibly takes place through this process via
previous formation of the anilines by decomposition of the
isocyanates in the presence of moist solvents. In order to test
this hypothesis in regard to the first species, bis-imines 13a,b were
prepared in high yields by treatment of 4a with an excess of
anilines 12a,b in MeOH as the solvent under mild conditions
(Scheme 4). Then, the former were reacted with phenylisocya-
nate (5a) under the same reaction conditions as those used in
Table 1. However, no dienes 8a and 8e were detected in the crude
mixture. Even more, reaction of 13a with N,N-diphenylurea
(11a) was also assayed without obtaining the expected product.
For the preparation of enamines 14a,b, α-diketones 4a,b were
treated with aniline (12a) in the presence of Lewis (AlCl3) or
Brønsted (p-TsOH, AcOH) acids (Scheme 5). Yet, in the case of
4a, only the corresponding imine 15a was obtained, while with
4b a mixture of the novel enamine 14b and imine 15b18 was
isolated in low yield. The yield of 14b was slightly improved
(35%) by stirring the reaction mixture and using p-TsOH as the
catalyst (12 h) in the presence of MeOH as the solvent. The (Z)
1
established by spectrometric analyses. The H NMR spectra
show, unlike dienes 1 where the chemical shifts of the four vinyl
protons are different,6b only two doublets (J = 2.1ꢀ2.7 Hz) with
chemical shifts ranging from 4.26 to 4.41 ppm for the out protons
H-6a and H-7a and from 4.77 to 4.87 ppm for the in protons
H-6b and H-7b. These chemical shifts are comparable to those
found for the signals of the vinyl protons of the enamide moiety
of dienes 1.6b Also, similar chemical shifts were observed from the
13C NMR signals corresponding to the latter (84.7ꢀ85.2 ppm),
to carbons C-6 and C-7 (82.6ꢀ83.8 ppm) of dienes 8, and to
carbons C-4 and C-5 (ca. 140 ppm). Unexpectedly, the chemical
shift (ca. 153 ppm) for carbon C-2 of dienes 8 was also close to
that of dienes 1, in spite of the presence of different heteroatoms
bonded to the carbonyl group.17 Signal assignment of the pairs
out protons, H-6a/H-7a, and in protons, H-6b/H-7b, was carried
out by NOE experiments. Thus, for diene 8a, when the aromatic
protons were irradiated, an enhancement was observed in the
shielded doublet attributed to the out protons H-6a/H-7a. On
the other hand, when the signal of the out protons H-6a/H-7a
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Scheme 4. Failed Synthesis of Dienes from Bis-imines
Scheme 6. Synthesis of Dienes 8a and 9aꢀc via α-Iminoke-
tone 15a
Scheme 5. Preparation of Enamines 14a,b and Imines 15a,b
dienes but also that this is the most efficient approach for
obtaining such interesting and novel exo-heterocyclic dienes.
1
It is noteworthy that the H NMR spectrum of nonsymme-
trical diene 9a displays only slightly different chemical shifts
(Δδ = 0.03 ppm) for the signals (doublet, J = 2.4 Hz) of the out
protons H-6a and H-7a as well as (Δδ = 0.01 ppm) for the signals
(doublet, J = 2.4 Hz) of the in protons H-6b and H-7b of the
diene moiety. These data suggest that the effects that can induce
the chemical shifts of these protons, e.g., the electron-donating
effect of the two nonequivalent nitrogen atoms (the enamidic
effect) and the shielding effect of the aryl rings, are almost
identical on the terminal carbons C-6 and C-7. Actually, the
electron density on the nitrogen atom is probably nearly
unperturbed by the π-electron density of the aryl ring, owing
to the fact that the latter should be almost orthogonal to the plane
of the heterocycle (see the calculated geometry of dienes 8a and
9a, Figure 1), as shown by X-ray diffraction analysis of dienes
1ꢀ3.6ꢀ8 The signal discrimination between protons H-6a and
H-6b as well as between protons H-7a and H-7b was carried out
by NOE experiments. An enhancement in the shielded signal
attributed to the out protons H-6a/H-7a was observed when the
aromatic protons were irradiated, indicating their spatial proxi-
mity. It is likely that the enamidic effect along with the well-
known anisotropic effect of the rigid dienic system are governing
the different chemical shifts between the in and the out protons,
as suggested for dienes 1 and 2.6b In contrast, attribution of the
signals by NOE was impossible in relation to the out protons
H-6a and H-7a as well as for the in protons H-6b and H-7b of
diene 9a due to the extremely small Δδ. However, for diene 9d
(see below) the doublet signals for each proton are separated
sufficiently to make this attribution.
Preparation of the series of symmetrical dienes 8bꢀe with N,
N0-diaryl substituents was attained when the α-iminoketones
15cꢀf were submitted to addition of the corresponding iso-
cyanates 5bꢀe, leading to the desired dienes in good yields
(Scheme 7). α-Iminoketones 15cꢀf were obtained under similar
conditions to those used for 15a in fairly good yields by
condensing diacetyl (4a) with the respective anilines 12bꢀe.
Further combination between α-iminoketones and aryliso-
cyanates could be the pathway for the synthesis of other series of
nonsymmetrical dienes. For example, when the reaction is
carried out between α-iminoketones 15c and 15g with aryliso-
cyanates 5d and 5e, dienes 9dꢀf were satisfactorily prepared
configuration of 14b was established by NOE experiments, since
there was even greater enhancement of the signal attributed to
the phenyl group by irradiating the vinylic methyl group.19 The
fact that the procedure failed to yield enamine 14a supports the
results previously reported in which evidence was given of the
difficulty in preparing enamines from primary amines and methyl
ketones.20 Although enamine 14b already possesses the enamine
moiety of dienes 8, reaction with isocyanate 5a in the presence of
the (Et3N) and dehydrating additive (Li2CO3) was unable to
furnish the desired product, even by irradiation with MW.
Finally, we tested the in situ generation of monoimines 15 as
intermediates involved in formation of dienes 8aꢀd. Thus, α-
iminoketone 15a was prepared in good yield by following the
same mild conditions (20 °C, 12 h) as those used for bis-imines
13 with α-diketone 4a but with only 1.2 mol equiv of aniline
(12a) (Scheme 6). Surprisingly and in contrast with the previous
processes, reaction of 15a with isocyanate 5a efficiently produced
the desired symmetric diene 8a in good yield. This methodology
was also efficient for affording the novel unsymmetrical imida-
zolidin-2-one dienes 9aꢀc in fairly good yields, starting from
isocyanates 5b and 5e,f (Scheme 6). Unlike with the reactions of
Table 1, where moist reagents and solvents were used, in this
method the conditions were strictly anhydrous. When numerous
dehydrating agents were tested (MgSO4, Na2SO4, K2CO3,
molecular sieves, etc.) in order to preserve these conditions,
Li2CO3 provided the best yields, thus proving itself to be the
most efficient. Although these dienes are not particularly light
sensitive in the solid state, the solution-medium process must be
performed in the dark to avoid radical-promoted polymerization.
Actually, dienes 8 and 9 are stable solids at room temperature for
several days (some additional slight spots are detected by tlc) and
can be kept refrigerated (4 °C) for months. However, they are
not very stable in solution, suffering polymerization at room
temperature in a few hours, for example, when in EtOAc or
CH2Cl2 as solvents.
Therefore, this methodology gives evidence not only that
imines are the most probable intermediates in formation of these
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Figure 1. Geometry of Dienes 8a and 9a Fully Optimized by the B3LYP/6-31G** Calculation Method.
Scheme 7. Synthesis of Symmetric Dienes 8bꢀe
Scheme 8. Preparation of Nonsymmetrical Dienes 9dꢀg
(Scheme 8). In contrast, use of alkylisocyanates such as 5g
provided the corresponding diene 9g, which was detected by
1H NMR of the crude mixtures yet it was unstable to the isolation
conditions, suffering rapid polymerization. Diene 9g was trapped
in situ by adding N-phenylmaleimide (16) at 0ꢀ20 °C to
efficiently furnish the corresponding adduct 17a.
Interestingly, these results would support the idea that the
chemical stability of dienes 8 and 9 seems to be associated with
the N-aryl groups, since the N-alkyl N-aryl diene 9g was less
stable. However, the carbonyl group of the heterocycle would
also contribute to this stability, because the diene moiety is
more structurally related to an enamidic than an enaminic
moiety. The latter should be much more reactive than the former
with different eletrophilic species, such as protons, which can
promote their decomposition or polymerization.20b
The reactivity of these dienes was evaluated in the DielsꢀAlder
cycloaddition of diene 8a with methyl vinyl ketone (18a). Under
catalyst-free conditions, in CH2Cl2 as the solvent and at room
temperature, the reactiondid not occur. Whenthetemperature was
increased to 60ꢀ80 °C, a low-yield conversion and decomposition
of the dienewere observed. However, under Lewis acid catalysis the
expected adduct 19a was afforded in high yield (Scheme 9).
Interestingly, the reaction took place at a low temperature for 25
min, supporting the idea that these dienes must be more reactive
than oxazolidin-2-one dienes 1ꢀ3 due to the presence of two
strong electron-releasing nitrogen atoms attached to the diene.
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Scheme 9. DielsꢀAlder Additions of Dienes 8a and 9b, and Synthesis of Benzimidazol-2-ones 10a,b
Table 2. Ab Initio RHF/6-31G** Calculations of Energies (eV) and Coefficients (Ci) of the Frontier Molecular Orbitals for Dienes
1a, 2a, 8a, 9a, 9h, and 22 and Dienophile 18aa
HOMO
LUMO
compdb
E (eV)
C1
C2
C3
C4
ΔCic
E (eV)
C1
C2
C3
C4
ΔCic
1ad
2ad
8a
ꢀ8.8051
ꢀ8.5610
ꢀ7.9496
ꢀ7.8805
ꢀ8.1050
ꢀ8.1874
ꢀ10.4868
0.246
ꢀ0.257
0.250
0.164
ꢀ0.199
0.135
ꢀ0.209
0.198
ꢀ0.326
0.320
0.080
0.063
2.9065
3.1035
2.8602
2.8975
3.0640
3.7519
2.9217
0.263
0.274
0.244
0.243
0.260
0.286
ꢀ0.245
ꢀ0.222
ꢀ0.232
ꢀ0.231
ꢀ0.244
ꢀ0.206
ꢀ0.208
ꢀ0.245
ꢀ0.245
ꢀ0.232
ꢀ0.234
ꢀ0.249
ꢀ0.206
ꢀ0.280
0.258
0.248
0.244
0.245
0.258
0.286
0.254
ꢀ0.005
ꢀ0.026
0.000
ꢀ0.135
0.126
ꢀ0.250
0.238
0.000
9a
ꢀ0.247
ꢀ0.290
ꢀ0.317
0.346
ꢀ0.131
ꢀ0.171
ꢀ0.233
0.366
ꢀ0.009
ꢀ0.014
0.000
0.002
9h
0.170
0.304
ꢀ0.002
0.000
22
18ad
0.233
0.317
ꢀ0.039
ꢀ0.221
ꢀ0.020
0.311
b
0.103
a
0
These are the values of the pz coefficients; the relative pz contributions and their ΔCi are analogous. For the most stable planar s-cis conformation for
olefin 18a. c Carbon 4 ꢀ carbon 1 for the dienes; carbon 1 ꢀ carbon 2 for the dienophile. d Reference 6b.
Further evidence of the enhanced reactivity of dienes 8 or 9 is the
fact that diene 1a (Ar= Ph) reacts with N-phenylmaleimide (16) at
180 °C for 1 h6b while diene 8a undergoes cycloaddition to 16 at
0 °C for 1 h to give adduct 17b (Scheme 9).
Similarly, reaction of diene 8a with acrolein (18b), under
analogous conditions of catalysis and low temperature (ꢀ78 °C)
for 5 min, gave rise to adduct 19b in 93% yield. In contrast, when
the same reaction was carried out at room temperature, only a tar
residue was isolated.
Reaction between the nonsymmetrical diene 9b with 18a
under similar conditions to those used for diene 8a afforded an
inseparable mixture of adducts 19c/20 in a modest regioselec-
tivity (not assigned) (Scheme 9). As evidenced by the 1H NMR
chemical shift data of the protons of the diene moiety (vide
supra), this low regioselectivity is probably due to the fact that the
substituents in the aromatic rings attached to the nitrogen atoms
do not display a significant electronic effect to induce a differ-
entiable perturbation on the diene terminal carbon atoms.
With the aim of exploring a preliminary synthetic application
of these molecules, adducts 19a,b were converted into the aro-
matic derivatives benzo[d]imidazol-2-ones 10a,b by a DDQ-
promoted oxidation (Scheme 9), providing the products as stable
white powders in good yield.
Frontier molecular orbital (FMO) theory was used to ratio-
nalize the reactivity and regioselectivity of the new dienes 8 and 9
in the DielsꢀAlder cycloaddition, in comparison to dienes 1a
and 2a. The geometries of the latter as well that of dienophile 18a
have been previously calculated,6b while the geometries of dienes
8a and 9a were calculated and optimized using the B3LYP/6-
31G**21 method without any symmetry constraints. These
geometries were employed for single-point calculation of en-
ergies and coefficients of the FMOs by using the RHF/6-31G**
basis set.22 As expected, like dienes 1 and 2, the aryl rings of
dienes 8a and 9a adopt a preferential noncoplanar conformation
with respect to the plane of the heterocycle and that of the
exocyclic diene as well (Figure 1). This conformation inhibits the
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conjugation of the electron lone pairs of the nitrogen atoms with
the aryl rings. Therefore, as aforementioned, this would support
the hypothesis that no relevant π-electronic effects of the aryl
substituents, but instead only their weak inductive effects,23
should be transmitted onto the dienic moiety.
By using the same basis set, the energies of the FMOs were
calculated for both kinds of dienes and for cyclopentadiene (22),
the latter for the purpose of comparison with a well-known
reactive diene. The energy gaps for the possible interactions were
measured (Table 2), showing that the interaction between
HOMOdieneꢀLUMOdienophile (normal electronic demand) is
more favorable with respect to the LUMOdieneꢀHOMOdienophile
interaction (inverse electronic demand).
As expected, the presence of two nitrogen atoms attached to
the dienic moiety in dienes 8a and 9a results in a greater energy of
the HOMO, compared to the HOMO energy of diene 1 and
even to the HOMO energies of the methyl substituted diene 2 or
diene 22. Hence, the reactivity of dienes 8a and 9a should be
higher than the other ones. This is in agreement with the
experimental results in the particular case of dienes 1 and 8a,
compared to the cycloadditions to dienophile 16.
The low regioselectivity observed in the cycloaddition of
9b with 18a to yield the mixture of 19c/20 (Scheme 9) can be ex-
plained on the basis of the coefficient differences for the
HOMOdieneꢀLUMOdienophile interactions for the analogue
diene 9a (Table 2). Indeed, if the FMO coefficients of the diene
termini C1 and C4 are almost equal (ΔCi = 0.009, Table 2), only
a nonregioselective interaction with the coefficients of the dien-
ophile 18a can be expected. It seems that even for the more
differentiated diene 9h the regioselectivity should not be sig-
nificantly increased, since the calculated coefficients do not show
a large difference between the diene termini C1 and C4 (ΔCi =
0.014, Table 2). Nevertheless, taking into account the behavior
between dienes 1 and 2,6b the regioselectivity of dienes 8 or 9
may be largely improved by attaching electron-donating groups,
such as a methyl group, in one of the diene termini.
lamp. Flash column chromatography was performed over silica gel
(230ꢀ400 mesh). All air moisture-sensitive reactions were carried out
under nitrogen using oven-dried glassware. MeOH and toluene were
freshly distilled over sodium and methylene chloride over calcium
hydride prior to use. Acetone was dried by distillation after treatment
with 4 Å molecular sieves. Li2CO3 was dried overnight at 200 °C prior to
use. Triethylamine was freshly distilled from NaOH. All other reagents
were used without further purification.
(E,E)-N,N0-(Butane-2,3-diylidene)dianiline (13a). A mixture
of 4a (0.98 g, 11.4 mmol) and 12a (1.42 g, 15.3 mmol) in MeOH
(100 mL) was stirred at room temperature under N2 atmosphere for
12 h. The solid was filtered, washed with MeOH (3 ꢁ 15 mL), and dried
under vacuum to give 2.42 g (90%) of 13a as a yellow solid; Rf 0.73
(hexane/EtOAc, 4:1); mp 135ꢀ136 °C [Lit.24 138ꢀ139 °C]. IR (KBr)
1633, 1480, 1445, 1355, 1207, 1116, 1071, 809, 762, 695 cmꢀ1. 1H NMR
(300 MHz, CDCl3) δ 2.15 (s, 6H, CH3), 6.75ꢀ6.85 (m, 4H, H-2, H-20),
7.08ꢀ7.16 (m, 2H, H-4, H-40), 7.32ꢀ7.43 (m, 4H, H-3, H-30). 13C
NMR (75.4 MHz, CDCl3) δ 15.4 (CH3CdN), 118.7 (C-2, C-20), 123.8
(C-4, C-40), 128.9 (C-3, C-30), 150.9 (C-1, C-10), 168.3 (CH3CdN).
HRMS (EI) m/z [M+] calcd for C16H16N2: 236.1314. Found: 236.1316.
(E,E)-N,N0-(Butane-2,3-diylidene)bis(4-chloroaniline)
(13b). Following the procedure for 13a, a mixture of 4a (0.98 g, 11.4
mmol) and 12b (1.45 g, 11.4 mmol) in MeOH (100 mL) gave 3.30 g
(95%) of 13b as a yellow powder; Rf 0.77 (hexane/EtOAc, 4:1); mp
175ꢀ176 °C [Lit.25 176ꢀ177 °C]. IR (KBr) 1629, 1480, 1425, 1363,
1205, 1123, 1087, 845 cmꢀ1. 1H NMR (300 MHz, CDCl3) δ 2.13 (s,
6H, CH3), 6.68ꢀ6.76 (m, 4H, H-2, H-20), 7.28ꢀ7.38 (m, 4H, H-3,
H-30). 13C NMR (75.4 MHz, CDCl3) δ 15.4 (CH3CdN), 120.2 (C-2,
C-20), 129.1 (C-3, C-30), 129.3 (C-4, C-40), 149.2 (C-1, C-10), 168.7
(CH3CdN). HRMS (EI) m/z [M+] calcd for C16H14N2Cl2: 304.0534.
Found: 304.0541.
(Z)-3-(Phenylamino)pent-3-en-2-one (14b). A mixture of 4b
(0.95 g, 9.5 mmol) and p-TsOH (0.36 g, 2.1 mmol) in MeOH (150 mL)
was stirred at room temperature under N2 atmosphere for 0.5 h. Then,
12a (0.44 g, 4.7 mmol) was added, and the mixture was stirred at room
temperature for 12 h. The solvent was removed under vacuum, and the
residue was purified by column chromatography over silica gel (10 g/g of
crude, hexane/EtOAc, 98:2) to give 0.58 g (35%) of 14b as a pale yellow
oil; Rf 0.55 (hexane/EtOAc, 4:1). IR (film) 1717, 1631, 1495, 1412,
1256, 840, 759 cmꢀ1. 1H NMR (300 MHz, CDCl3) δ 1.70 (d, J = 7.2 Hz,
3H, H-5), 2.40 (s, 3H, CH3CO), 6.06 (br s, 1H, NH), 6.35 (q, J = 7.2 Hz,
1H, H-4), 6.63ꢀ6.71 (m, 2H, H-20), 6.79ꢀ6.87 (m, 1H, H-40),
7.17ꢀ7.25 (m, 2H, H-30). 13C NMR (75.4 MHz, CDCl3) δ 15.3 (C-
5), 24.8 (C-1), 116.4 (C-20), 119.8 (C-40), 124.9 (C-4), 128.8 (C-30),
139.0 (C-3), 143.7 (C-10), 196.5 (C-2). MS (70 eV) m/z 175 (M+, 13),
132 (100), 103 (9), 77 (94), 51 (45). HRMS (EI) m/z [M+] calcd for
C11H13NO: 175.0997. Found: 175.0998.
’ CONCLUSION
In summary, we developed an efficient method to prepare the
novel symmetric exo-2-imidazolidinone dienes 8aꢀe. Unsym-
metrical dienes 9aꢀf and in situ formation of 9g were also made
available by this methodology. The mechanistic study provided
strong evidence that the key intermediate in heterocyclic ring
formation corresponded to an α-ketoimino derivative, 15. The
synthetic potential of these dienes was demonstrated, since diene
8a can easily undergo DielsꢀAlder cycloaddition to give the
corresponding adducts, which in turn can be transformed into
the synthetically attractive heterocycle benzimidazol by aroma-
tization. Further studies of the preparation of a wide spectrum of
substituted dienes and their use in the synthesis of a variety of
heterocycles are currently under active investigation.
General Method for the Preparation of α-Ketoimines
15aꢀg. (E)-3-(Phenylimino)butan-2-one (15a). A mixture of 4a
(0.98 g, 11.4 mmol) and 12a (1.12 g, 11.4 mmol) in MeOH
(150 mL) was stirred at room temperature under N2 atmosphere for
12 h. The solvent was removed under vacuum, and the residue was
purified by column chromatography over silica gel (10 g/g crude,
hexane/EtOAc, 98:2) to give 1.46 g (80%) of 15a as a pale yellow
oil;26 Rf 0.65 (hexane/EtOAc, 4:1). IR (film) 1700, 1593, 1485, 1355,
1117, 762, 695 cmꢀ1. 1H NMR (300 MHz, CDCl3) δ 1.96 (s, 3H, H-4),
2.52 (s, 3H, H-1), 6.72ꢀ6.83 (m, 2H, H-20), 7.10ꢀ7.19 (m, 1H, H-40),
7.33ꢀ7.42 (m, 2H, H-30). 13C NMR (75.4 MHz, CDCl3) δ 14.0 (C-4),
24.6 (C-1), 118.6 (C-20), 124.7 (C-40), 129.0 (C-30), 149.4 (C-10), 165.9
(C-3), 180.0 (C-2). HRMS (EI) m/z [M+] calcd for C10H11NO:
161.0841. Found: 161.0838.
’ EXPERIMENTAL SECTION
General. Melting points (uncorrected) were determined with a
capillary melting point apparatus. 1H (300 or 500 MHz) and 13C (75.4
or 125 MHz) NMR spectra were recorded with TMS as an internal
standard. Assignment of the NMR signals was made by HMQC and
HMBC 2D methods. Mass spectra (MS) and high-resolution mass
spectra (HRMS) were obtained in the electron impact (EI) (70 eV)
mode. Analytical thin-layer chromatography was carried out using silica
gel coated 0.25 plates, visualized by a long- and short-wavelength UV
(E)-2-(Phenylimino)pentan-3-one (15b). Following the procedure
for 15a, a mixture of 4b (0.95 g, 9.5 mmol) and 12a (0.88 g, 9.5 mmol) in
MeOH (150 mL) gave 1.41 g (85%) of 15b as a pale yellow oil;27 Rf 0.63
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(hexane/EtOAc, 4:1). IR (film) 1701, 1647, 1593, 1485, 1354, 1216,
1093, 782, 697 cmꢀ1. 1H NMR (300 MHz, CDCl3) δ 1.14 (t, J = 7.3 Hz,
3H, H-5), 1.95 (s, 3H, H-1), 3.00 (q, J = 7.3 Hz, 2H, H-4), 6.75 (d, J = 7.8
Hz, 2H, H-20), 7.11 (t, J = 6.9 Hz, 1H, H-40), 7.34 (t, J = 7.7 Hz, 2H, H-30).
13C NMR (75.4 MHz, CDCl3) δ 7.7 (C-5), 14.0 (C-4), 29.6 (C-1), 118.4
(C-20), 124.4 (C-40), 128.8 (C-30), 149.4 (C-10), 165.4 (C-2), 202.5 (C-
3). MS (70 eV) m/z 175 (M+, 12), 118 (100), 77 (78), 51 (34). HRMS
(EI) m/z [M+] calcd for C11H13NO: 175.0997. Found: 175.0994.
(E)-3-(4-Tolylimino)butan-2-one (15c). Following the procedure for
15a, a mixture of 4a (0.98 g, 11.4 mmol) and 12b (1.22 g, 11.4 mmol) in
MeOH (150 mL) gave 1.49 g (75%) of 15c as a pale yellow oil;26 Rf 0.61
(hexane/EtOAc, 4:1). IR (film) 2922, 1700, 1638, 1504, 1425, 1356,
1221, 1116, 840, 826, 750, 599 cmꢀ1. 1H NMR (500 MHz, CDCl3) δ
1.97 (s, 3H, H-4), 2.35 (s, 3H, CH3Ar), 2.51 (s, 3H, H-1), 6.68ꢀ6.70 (m,
2H, H-20), 7.16ꢀ7.19 (m, 1H, H-30). 13C NMR (125 MHz, CDCl3) δ
13.9 (C-4), 20.9 (CH3Ar), 24.6 (C-1), 118.9 (C-20), 129.5 (C-30), 134.4
(C-40), 146.8 (C-10), 165.7 (C-3), 200.6 (C-2). MS (70 eV) m/z 175
(M+, 28), 158 (9), 133 (12), 132 (100), 91 (41), 89 (5), 65 (8). HRMS
(EI) m/z [M+] calcd for C11H13NO: 175.0997. Found: 175.0998.
(E)-3-(4-Methoxyphenylimino)butan-2-one (15d). Following the
procedure for 15a, a mixture of 4a (0.98 g, 11.4 mmol) and 12c (1.40
g, 11.4 mmol) in MeOH (150 mL) gave 1.77 g (81%) of 15d as a pale
yellow oil;26 Rf 0.60 (hexane/EtOAc, 4:1). IR (film) 1698, 1603, 1503,
1355, 1244, 1115, 1034, 842, 748 cmꢀ1. 1H NMR (300 MHz, CDCl3) δ
2.00 (s, 3H, H-4), 2.49 (s, 3H, H-1), 3.79 (s, 3H, OMe), 6.76ꢀ6.81 (m,
2H, H-30), 6.88ꢀ6.93 (m, 2H, H-20). 13C NMR (75.4 MHz, CDCl3) δ
13.7 (C-4), 24.4 (C-1), 55.1 (OMe), 113.9 (C-30), 121.0 (C-20), 142.0
(C-10), 157.0 (C-40), 165.0 (C-3), 200.4 (C-2). MS (70 eV) m/z 191
(M+, 12), 148 (100), 105 (13), 92 (52), 77 (12), 64 (26). HRMS (EI)
m/z [M+] calcd for C11H13NO2: 191.0946. Found: 191.0956.
(M+, 5), 132 (100), 91 (77), 89 (26), 65 (64), 51 (12). HRMS (EI) m/z
[M+] calcd for C11H13NO: 175.0997. Found: 175.0995.
4,5-Dimethylene-1,3-diphenylimidazolidin-2-one
(8a). Method A. A mixture of 4a (0.49 g, 5.7 mmol), Et3N (1.44 g, 14.3
mmol), and Li2CO3 (4.20 g, 56.8mmol) intoluene (30 mL) was stirred at
20 °C under N2 for 1.5 h in the dark. Then, 5a (1.69 g, 14.2 mmol) in
toluene (30 mL) was added dropwise, and the mixture was stirred at room
temperature for 24 h. The mixture was filtered over Celite and washed
with CH2Cl2 (2 ꢁ 20 mL). The solvent was removed under vacuum, and
the crude was purified by column chromatography over silica gel (10 g/g
of crude, hexane/EtOAc, 95:5) to give 8a (0.37 g, 25%) as a white solid.
Method B. Following method A, a mixture of 15a (0.300 g, 1.86
mmol), Et3N (0.570 g, 5.60 mmol), Li2CO3 (1.00 g, 13.5 mmol), and 5a
(0.560 g, 4.71 mmol) in anhydrous toluene (75 mL) was stirred at room
temperature under N2 for 24 h in the dark to give 8a (0.37 g, 75%) as a
white solid. Rf 0.61 (hexane/EtOAc, 8:2); mp 75ꢀ76 °C. IR (film) 1712,
1
1600, 1541, 1499, 1447, 1403, 1315, 1228, 1068, 756, 692 cmꢀ1. H
NMR (300 MHz, CDCl3) δ 4.37 (d, J = 2.4 Hz, 2H, H-6a, H-7a), 4.82
(d, J = 2.4 Hz, 2H, H-6b, H-7b), 7.34ꢀ7.45 (m, 6H, ArH), 7.46ꢀ7.53
(m, 4H, ArH). 13C NMR (75.4 MHz, CDCl3) δ 82.9 (C-6, C-7), 127.5
(ArH), 127.9 (ArH), 129.4 (ArH), 134.2 (Ar), 140.0 (C-4, C-5), 153.5
(C-2). MS (70 eV) m/z 262 (M+, 69), 249 (100), 191 (24), 128 (12),
115 (18), 76 (12), 69 (18). HRMS (FAB) m/z [M + 1]+ calcd for
C17H15N2O: 263.1184. Found: 263.1180.
4,5-Dimethylene-1,3-bis(4-tolyl)imidazolidin-2-one
(8b). Method A. Following method A for preparation of 8a, a mixture
of 4a (0.25 g, 2.9 mmol), Et3N (0.71 g, 7.0 mmol), Li2CO3 (2.00 g, 27.0
mmol), and 5b (0.940 g, 7.07 mmol) in toluene (30 mL) was stirred at
room temperature under N2 for 24 h in the dark to give 8b (0.30 g, 35%)
as a white solid.
(E)-3-(3-Chlorophenylimino)butan-2-one (15e). Following the pro-
cedure for 15a, a mixture of 4a (0.98 g, 11.4 mmol) and 12d (1.46 g, 11.4
mmol) in MeOH (150 mL) gave 1.45 g (65%) of 15e as a pale yellow
oil;28 Rf 0.75 (hexane/EtOAc, 4:1). IR (film) 1703, 1648, 1590, 1468,
1357, 1118, 865, 790, 682, 627 cmꢀ1. 1H NMR (300 MHz, CDCl3) δ
1.96 (s, 3H, H-4), 2.50 (s, 3H, H-1), 6.65 (ddd, J = 8.0, 2.0, 1.0 Hz, 1H,
H-60), 6.79 (t, J = 2.0 Hz, 1H, H-20), 7.12 (ddd, J = 8.0, 2.0, 1.0 Hz, 1H,
H-40), 7.30 (t, J = 8.0 Hz, 1H, H-50). 13C NMR (75.4 MHz, CDCl3) δ
14.0 (C-4), 24.4 (C-1), 116.7 (C-60), 118.7 (C-20), 124.5 (C-40), 130.2
(C-50), 134.7 (C-30), 150.7 (C-10), 166.7 (C-3), 199.8 (C-2). MS (70
eV) m/z 195 (M+, 5), 152 (100), 111 (42), 85 (4), 75 (19), 51 (4).
HRMS (EI) m/z [M+] calcd for C10H10ClNO: 195.0451. Found:
195.0451.
(E)-3-(4-Chlorophenylimino)butan-2-one (15f). Following the pro-
cedure for 15a, a mixture of 4a (0.98 g, 11.4 mmol) and 12e (1.46 g, 11.4
mmol) in MeOH (150 mL) gave 1.33 g (60%) of 15f as a pale yellow
oil;29 Rf 0.59 (hexane/EtOAc, 4:1). IR (film) 2965, 1702, 1638, 1492,
1359, 1311, 1118, 844, 826, 651 cmꢀ1. 1H NMR (300 MHz, CDCl3) δ
1.96 (s, 3H, H-4), 2.50 (s, 3H, H-1), 6.65ꢀ6.74 (m, 2H, H-20),
7.32ꢀ7.39 (m, 1H, H-30). 13C NMR (75.4 MHz, CDCl3) δ 14.0 (C-
4), 24.5 (C-1), 120.2 (C-20), 124.7 (C-40), 129.0 (C-30), 149.1 (C-10),
166.5 (C-3), 200.1 (C-2). MS (70 eV) m/z 195 (M+, 3), 154 (31), 152
(100), 111 (89), 75 (93). HRMS (EI) m/z [M+] calcd for C10H10ClNO:
195.0451. Found: 195.0452.
(E)-3-(3-Tolylimino)butan-2-one (15g). Following the procedure for
15a, a mixture of 4a (0.98 g, 11.4 mmol) and 12f (1.22 g, 11.4 mmol) in
MeOH (150 mL) gave 1.34 g (84%) of 15g as a pale yellow oil;28 Rf 0.75
(hexane/EtOAc, 4:1). IR (film) 1702, 1645, 1600, 1583, 1482, 1422,
1356, 1117, 936, 898, 795, 693 cmꢀ1. 1H NMR (300 MHz, CDCl3) δ
1.94 (s, 3H, H-4), 2.34 (s, 3H, CH3Ar), 2.49 (s, 3H, H-1), 6.53ꢀ6.59 (m,
2H, H-20, H-60), 6.94 (dd, J = 7.5, 0.6 Hz, 1H, H-40), 7.23 (t, J = 7.5 Hz,
1H, H-50). 13C NMR (75.4 MHz, CDCl3) δ 13.7 (C-4), 21.2 (CH3Ar),
24.3 (C-1), 115.4 (C-60), 119.1 (C-20), 125.2 (C-40), 128.7 (C-50), 138.7
(C-30), 149.4 (C-10), 165.6 (C-3), 200.2 (C-2). MS (70 eV) m/z 175
Method B. Following method B for preparation of 8a, a mixture of 15c
(0.250 g, 1.43 mmol), Et3N (0.360 g, 3.57 mmol), Li2CO3 (1.00 g, 13.5
mmol), and 5b (0.570 g, 4.29 mmol) in anhydrous toluene (70 mL) was
stirred at room temperature under N2 for 24 h in the dark to give 8b
(0.31 g, 75%) as a white solid. Rf 0.58 (hexane/EtOAc, 8:2); mp
119ꢀ120 °C. IR (KBr) 1732, 1629, 1512, 1403, 1376, 1258, 1170,
845, 813 cmꢀ1. 1H NMR (300 MHz, CDCl3) δ 2.39 (s, 6H, CH3Ar),
4.30 (d, J = 2.3 Hz, 2H, H-6a, H-7a), 4.78 (d, J = 2.3 Hz, 2H, H-6b,
H-7b), 7.27 (s, 8H, ArH). 13C NMR (75.4 MHz, CDCl3) δ 21.2
(CH3Ar), 82.6 (C-6, C-7), 127.4 (ArH), 130.0 (ArH), 131.6 (Ar), 137.8
(Ar), 140.3 (C-4, C-5), 153.7 (C-2). HRMS (EI) m/z [M+] calcd for
C19H18N2O: 290.1419. Found: 290.1412.
1,3-bis(4-Methoxyphenyl)-4,5-dimethyleneimidazolidin-
2-one (8c). Method A. Following method A for preparation of 8a, a
mixture of 4a (0.24 g, 2.8 mmol), Et3N (0.71 g, 7.0 mmol), Li2CO3 (2.50 g,
33.8 mmol), and 5c (1.06 g, 7.1 mmol) in toluene (30 mL) was stirred at
room temperature under N2 for 24 h in the dark to give 8c (0.32 g, 36%)
as a pale yellow solid.
Method B. Following method B for preparation of 8a, a mixture of
15d (0.250 g, 1.31 mmol), Et3N (0.330 g, 3.27 mmol), Li2CO3 (0.96 g,
13.0 mmol), and 5c (0.580 g, 3.89 mmol) in anhydrous toluene (65 mL)
was stirred at room temperature under N2 for 24 h in the dark to give 8c
(0.30 g, 71%) as a pale yellow solid. Rf 0.57 (hexane/EtOAc, 8:2); mp
160ꢀ161 °C. IR (KBr) 1726, 1623, 1512, 1410, 1300, 1253, 1169, 844,
825 cmꢀ1. 1H NMR (300 MHz, CDCl3) δ 3.83 (s, 6H, OCH3), 4.26 (d,
J = 2.1 Hz, 2H, H-6a, H-7a), 4.77 (d, J = 2.1 Hz, 2H, H-6b, H-7b),
6.95ꢀ7.02 (m, 4H, ArH), 7.25ꢀ7.33 (m, 4H, ArH). 13C NMR (75.4
MHz, CDCl3) δ 55.4 (OMe), 82.6 (C-6, C-7), 114.7 (ArH), 126.8 (Ar),
128.9 (ArH), 140.6 (C-4, C-5), 154.0 (C-2), 159.0 (Ar). HRMS (EI)
m/z [M+] calcd for C19H18N2O3: 322.1318. Found: 322.1330.
1,3-Bis(3-chlorophenyl)-4,5-dimethyleneimidazolidin-2-
one (8d). Method A. Following method A for preparation of 8a, a
mixture of 4a (0.24 g, 2.8 mmol), Et3N (0.71 g, 7.0 mmol), Li2CO3 (2.50 g,
33.8 mmol), and 5d (1.07 g, 7.0 mmol) in toluene (30 mL) was stirred at
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room temperature under N2 for 24 h in the dark to give 8d (0.46 g, 50%)
as a white solid.
4,5-Dimethylene-1-phenyl-3-(3-tolyl)imidazolidin-2-one
(9c). Following method B for preparation of8a, a mixture of 15a (0.220 g,
1.37 mmol), Et3N (0.420 g, 4.16 mmol), Li2CO3 (1.01 g, 13.7 mol), and
5f (0.460 g, 3.46 mmol) in anhydrous toluene (40 mL) was stirred at
room temperature under N2 for 24 h in the dark to give 9c (0.24 g, 61%)
as a white solid. Rf 0.60 (hexane/EtOAc, 8:2); mp 111ꢀ112 °C. IR
Method B. Following method B for preparation of 8a, a mixture of 15e
(0.250 g, 1.28 mmol), Et3N (0.320 g, 3.17 mmol), Li2CO3 (0.95 g, 12.8
mmol), and 5d (0.590 g, 3.84 mmol) in anhydrous toluene (30 mL) was
stirred at room temperature under N2 for 24 h in the dark to give 8d
(0.30 g, 70%) as a white solid. Rf 0.61 (hexane/EtOAc, 8:2); mp
137ꢀ138 °C. IR (KBr) 1719, 1635, 1590, 1481, 1436, 1407, 1253,
1212, 1132, 851, 790 cmꢀ1. 1H NMR (300 MHz, CDCl3) δ 4.41 (d, J =
2.7 Hz, 2H, H-6a, H-7a), 4.87 (d, J = 2.7 Hz, 2H, H-6b, H-7b),
7.29ꢀ7.46 (m, 8H, ArH). 13C NMR (75.4 MHz, CDCl3) δ 83.8 (C-
6, C-7), 125.7 (C-13, C-130), 127.8 (C-9, C-90), 128.3 (C-11, C-110),
130.4 (C-12, C-120), 135.0 (C-8, C-80), 135.2 (C-10, C-100), 139.3 (C-4,
C-5), 152.8 (C-2). MS (70 eV) m/z 332 (M+ + 1, 100), 331 (M+, 74),
298 (28), 297 (41), 262 (12), 116 (13). HRMS (EI) m/z [M+] calcd for
C17H12N2OCl2: 330.0327. Found: 330.0364.
1
(KBr) 1719, 1632, 1492, 1406, 1263, 1231, 1181, 849, 698 cmꢀ1. H
NMR (300 MHz, CDCl3) δ 2.38 (s, 3H, CH3Ar), 4.34 (d, J = 3.1 Hz,
1H, H-6a or H-7a), 4.35 (d, J = 3.1 Hz, 1H, H-7a or H-6a), 4.80 (d, J =
2.4 Hz, 2H, H-6b, H-7b), 7.14ꢀ7.50 (m, 9H, ArH). 13C NMR (75.4
MHz, CDCl3) δ 21.3 (CH3Ar), 82.8 (C-6), 82.9 (C-7), 124.5 (ArH),
127.5 (ArH), 127.8 (ArH), 128.2 (ArH), 128.8 (ArH), 129.2 (ArH),
129.4 (ArH), 134.1 (Ar), 134.3 (Ar), 139.4 (Ar), 140.0 (C-4 or C-5),
140.1 (C-5 or C-4), 153.6 (C-2). HRMS (FAB) m/z [M + 1]+ calcd for
C18H17N2O: 277.1341. Found: 277.1341.
1-(3-Chlorophenyl)-4,5-dimethylene-3-(4-tolyl)imidazolidin-
2-one (9d). Following method B for preparation of 8a, a mixture of 15c
(1.00 g, 5.7 mmol), Et3N (1.44 g, 14.3 mmol), Li2CO3 (4.22 g, 0.057
mol), and 5d (2.61 g, 17.1 mmol) in anhydrous toluene (200 mL) was
stirred at room temperature under N2 for 24 h in the dark to give 9d
(1.47 g, 83%) as a white solid. Rf 0.47 (hexane/EtOAc, 8:2); mp
136ꢀ137 °C. IR (KBr) 1717, 1632, 1517, 1484, 1409, 1255, 1212,
1131, 853, 820, 786 cmꢀ1. 1H NMR (500 MHz, CDCl3) δ 2.39 (s, 3H,
CH3Ar), 4.33 (d, J = 2.5 Hz, 1H, H-7a), 4.39 (d, J = 2.5 Hz, 1H, H-6a),
4.81 (d, J = 2.5 Hz, 2H, H-7b), 4.84 (d, J = 2.5 Hz, 2H, H-6b), 7.24ꢀ7.30
(m, 4H, ArH), 7.30ꢀ7.35 (m, 2H, ArH), 7.40 (t, J = 8.0 Hz, 1H, ArH),
7.44 (t, J = 8.0 Hz, 1H, ArH). 13C NMR (125 MHz, CDCl3) δ 21.2
(CH3Ar), 83.1 (C-6 or C-7), 83.2 (C-7 or C-6), 125.7 (ArH), 127.3
(ArH), 127.8 (ArH), 128.0 (ArH), 130.1 (ArH), 130.3 (ArH), 131.3
(Ar), 134.8 (Ar), 135.5 (Ar), 138.1 (Ar), 139.6 (C-4 or C-5), 140.0 (C-5
or C-4), 153.3 (C-2). MS (70 eV): m/z 310 (M+, 39), 297 (19), 140
(59), 133 (59), 105 (39), 81 (99), 77 (100). HRMS (EI) m/z [M+]
calcd for C18H15ClN2O: 310.0873. Found: 310.0873.
1,3-Bis(4-chlorophenyl)-4,5-dimethyleneimidazolidin-2-
one (8e). Following method B for preparation of 8a, a mixture of 15f
(0.250 g, 1.28 mmol), Et3N (0.320 g, 3.17 mmol), Li2CO3 (0.95 g, 12.8
mmol), and 5e (0.490 g, 3.19 mmol) in anhydrous toluene (30 mL) was
stirred at room temperature under N2 for 24 h in the dark to give 8e
(0.31 g, 73%) as a white solid. Rf 0.56 (hexane/EtOAc, 8:2); mp
162ꢀ163 °C. IR (KBr) 1713, 1632, 1498, 1397, 1257, 1132, 1094,
837, 815, 656 cmꢀ1. 1H NMR (500 MHz, CDCl3) δ 4.36 (d, J = 2.5 Hz,
2H, H-6a, H-7a), 4.84 (d, J = 2.5 Hz, 2H, H-6b, H-7b), 7.32ꢀ7.37 (m,
4H, ArH), 7.44ꢀ7.49 (m, 4H, ArH). 13C NMR (125 MHz, CDCl3) δ
83.4 (C-6, C-7), 128.8 (C-9, C-90), 129.7 (C-10, C-100), 132.6 (Ar),
133.8 (Ar), 139.5 (C-4, C-5), 153.1 (C-2). MS (70 eV) m/z 331 (M+,
100), 329 (45), 297 (26), 295 (78), 294 (20), 260 (17), 232 (12), 205
(12), 178 (10), 115 (17), 75 (18). Anal. Calcd for C17H12Cl2N2O: C,
61.65; H, 3.65; N, 8.46. Found: C, 61.61; H, 3.73; N, 8.16.
4,5-Dimethylene-1-phenyl-3-(4-tolyl)imidazolidin-2-one
(9a). Following method B for preparation of8a, a mixture of15a(1.000 g,
6.21 mmol), Et3N (2.150 g, 21.29 mmol), Li2CO3 (4.59 g, 62.1 mmol),
and 5b (2.480 g, 18.65 mmol) in anhydrous toluene (200 mL) was
stirred at room temperature under N2 for 24 h in the dark to give 9a
(1.38 g, 80%) as a white solid. Rf 0.42 (hexane/EtOAc, 8:2); mp
144ꢀ145 °C. IR (KBr) 1717, 1632, 1517, 1413, 1256, 1130, 850,
756 cmꢀ1. 1H NMR (300 MHz, CDCl3) δ 2.38 (s, 3H, CH3Ar), 4.32 (d,
J = 2.4 Hz, 1H, H-6a or H-7a), 4.35 (d, J = 2.4 Hz, 1H, H-7a or H-6a),
4.80 (t, J = 2.4 Hz, 2H, H-6b, H-7b), 7.28 (s, 4H, ArH), 7.32ꢀ7.52 (m,
5H, ArH). 13C NMR (75.4 MHz, CDCl3) δ 21.2 (CH3Ar), 82.7 (C-6,
C-7), 127.3 (ArH), 127.5 (ArH), 127.8 (ArH), 129.3 (ArH), 129.4 (Ar),
130.0 (ArH), 131.4 (Ar), 134.2 (Ar), 137.8 (ArH), 140.0 (C-5), 140.1
(C-4), 153.6 (C-2). MS (70 eV): m/z 276 (M+, 89), 275 (89), 261 (76),
179 (100), 151 (81), 133 (45), 120 (28), 107 (82), 91 (28), 77 (40).
HRMS (EI) m/z [M+] calcd for C18H16N2O: 276.1263. Found:
276.1264.
1-(4-Chlorophenyl)-4,5-dimethylene-3-phenylimidazoli-
din-2-one (9b). Following method B for preparation of 8a, a mixture
of 15a (0.200 g, 1.24 mmol), Et3N (0.380 g, 3.76 mmol), Li2CO3 (0.92 g,
12.4 mmol), and 5e (0.480 g, 3.13 mmol) in anhydrous toluene (40 mL)
was stirred at room temperature under N2 for 24 h in the dark to give 9b
(0.25 g, 67%) as a white solid. Rf 0.63 (hexane/EtOAc, 8:2); mp
150ꢀ151 °C. IR (KBr) 1717, 1631, 1595, 1495, 1412, 1256, 1213,
1130, 840 cmꢀ1. 1H NMR (300 MHz, CDCl3) δ 4.36 (d, J = 2.7 Hz, 1H,
H-6a or H-7a), 4.37 (d, J = 2.7 Hz, 1H, H-7a or H-6a), 4.83 (d, J = 2.7 Hz,
1H, H-6b or H-7b), 4.84 (d, J = 2.7 Hz, 1H, H-7b or H-6b), 7.35ꢀ7.55
(m, 9H, ArH). 13C NMR (75.4 MHz, CDCl3) δ 83.0 (C-6), 83.3 (C-7),
127.5 (ArH), 128.0 (ArH), 128.8 (Ar), 129.5 (ArH), 129.7 (Ar), 134.0
(Ar, ArH), 139.7 (C-4) 139.8 (C- 5), 152.8 (C-2). MS (70 eV): m/z 297
(M+ + 1, 40), 296 (M+, 70), 295 (94), 285 (89), 279 (23), 189 (14), 138
(27), 118 (70), 105 (100), 90 (27). HRMS (EI) m/z [M+] calcd for
C17H13ClN2O: 296.0716. Found: 296.0736.
1-(4-Chlorophenyl)-4,5-dimethylene-3-(4-tolyl)imidazolidin-
2-one (9e). Following method B for preparation of 8a, a mixture of 15c
(1.00 g, 5.7 mmol), Et3N (1.44 g, 14.3 mmol), Li2CO3 (4.22 g, 0.057
mol), and 5e (2.61 g, 17.1 mmol) in anhydrous toluene (200 mL) was
stirred at room temperature under N2 for 24 h in the dark to give 9e
(1.51 g, 85%) as a white solid. Rf 0.47 (hexane/EtOAc, 8:2); mp
135ꢀ136 °C. IR (KBr) 1717, 1632, 1496, 1413, 1091, 966, 817 cmꢀ1
.
1H NMR (500 MHz, CDCl3) δ 2.38 (s, 3H, CH3Ar), 4.32 (d, J = 2.5 Hz,
1H, H-7a), 4.34 (d, J = 3.0 Hz, 1H, H-6a), 4.80 (d, J = 2.5 Hz, 1H, H-7b),
4.82 (d, J = 3.0 Hz, 2H, H-6b), 7.23ꢀ7.31 (m, 4H, ArH), 7.33ꢀ7.38 (m,
2H, ArH), 7.43ꢀ7.47 (m, 2H, ArH). 13C NMR (125 MHz, CDCl3) δ
21.2 (CH3Ar), 82.9 (C-7), 83.2 (C-6), 127.5 (ArH), 128.8 (ArH), 129.5
(ArH), 129.7 (ArH), 132.8 (Ar), 133.6 (Ar), 134.1 (Ar), 138.1 (Ar),
139.7 (C-4 or C-5), 139.9 (C-5 or C-4), 153.3 (C-2). MS (70 eV) m/z
310 (M+, 25), 309 (100), 259 (13), 205 (13), 99 (12), 91 (38), 77 (45).
HRMS (EI) m/z [M+] calcd for C18H15ClN2O: 310.0873. Found:
310.0874.
1-(4-Chlorophenyl)-4,5-dimethylene-3-(3-tolyl)imidazolidin-
2-one (9f). Following method B for preparation of 8a, a mixture of 15g
(1.00 g, 5.7 mmol), Et3N (1.44 g, 14.3 mmol), Li2CO3 (4.22 g, 0.057
mol), and 5e (2.61 g, 17.1 mmol) in anhydrous toluene (200 mL) was
stirred at room temperature under N2 for 24 h in the dark to give 9f
(1.40 g, 80%) as a white solid. Rf 0.45 (hexane/EtOAc, 8:2); mp 145ꢀ
146 °C. IR (KBr) 1717, 1631, 1494, 1409, 1262, 1179, 1131, 1089, 856,
836, 791 cmꢀ1. 1H NMR (500 MHz, CDCl3) δ 2.39 (s, 3H, CH3Ar), 4.35
(d, J= 2.5 Hz, 2H, H-6a, H-7a), 4.81 (d, J= 2.5 Hz, 1H, H-6b or H-7b), 4.82
(d, J = 2.5 Hz, 1H, H-7b or H-6b), 7.16ꢀ7.21 (m, 3H, ArH), 7.32ꢀ7.38
(m, 3H, ArH), 7.43ꢀ7.47 (m, 2H, ArH). 13C NMR (125 MHz, CDCl3)
δ 21.2 (CH3Ar), 82.9 (C-6 or C-7), 83.3 (C-7 or C-6), 124.5 (ArH),
128.2 (ArH), 128.8 (2ArH), 128.9 (ArH), 129.2 (ArH), 129.6 (2ArH),
132.6 (Ar), 133.5 (Ar), 133.9 (Ar), 139.5 (Ar), 139.7 (C-4 or C-5), 140.0
7908
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ARTICLE
(C-5 or C-4), 153.3 (C-2). MS (70 eV): m/z 310 (M+, 20), 300 (27),
282 (49), 267 (60), 256 (75), 236 (35), 168 (27), 128 (20), 117 (100),
104 (41), 76 (40). HRMS (EI) m/z [M+] calcd for C18H15ClN2O:
310.0873. Found: 310.0872.
2.12ꢀ2.24 (m, 1H, H-6), 2.21 (s, 3H, CH3CO), 2.36ꢀ2.53 (m, 3H,
H-4, 2H-7), 2.60ꢀ2.72 (m, 1H, H-4), 2.76ꢀ2.84 (m, 1H, H-5),
7.28ꢀ7.49 (m, 10H, ArH). 13C NMR (75.4 MHz, CDCl3) δ 20.9,
22.9, 24.8, 28.2, 47.3, 116.1, 117.0, 126.1 (ArH), 126.2 (ArH), 127.0
(ArH), 127.1 (ArH), 129.0 (ArH), 129.1 (ArH), 134.8 (Ar), 135.0 (Ar),
152.1 (C-2), 209.3 (COCH3). MS (70 eV) m/z 332 (M+, 1), 265 (6),
237 (100), 223 (14), 195 (20), 159 (18), 133 (10), 109 (13), 91 (10).
HRMS (EI) m/z [M+] calcd for C21H20N2O2: 332.1525. Found:
332.1524.
1-(2-Chloroethyl)-6-phenyl-3-(3-tolyl)-4,4a,7a,8-tetrahy-
droimidazo[4,5-f]isoindole-2,5,7(1H,3H,6H)-trione (17a). A
mixture of 15g (0.300 g, 1.71 mmol), Et3N (0.430 g, 4.26 mmol),
Li2CO3 (1.27 g, 0.017 mol), and 5g (0.450 g, 9.51 mmol) in anhydrous
toluene (60 mL) was stirred at room temperature under N2 for 24 h in
the dark. The mixture was filtered over Celite, washing with CH2Cl2
(2 ꢁ 5 mL), and cooled to 0 °C. Then, 16 (0.330 g, 1.91 mmol) was
added, stirring to the same temperature under N2 for 1 h and to 20 °C for
3 h. The mixture was diluted with CH2Cl2 (15 mL) and poured into
H2O (10 mL). The organic layer was washed with a 5% aqueous solution
of NaHCO3 (2 ꢁ 5 mL) with a 5% aqueous solution of NH4Cl (2 ꢁ
15 mL) and dried (Na2SO4). The solvent was removed under vacuum,
and the crude was purified by column chromatography over silica gel (20 g,
hexane/EtOAc, 8:2) to give 17a (0.65 g, 87%) as a white solid. Rf 0.15
(hexane/EtOAc, 1:1); mp 74ꢀ75 °C. IR (KBr) 1710, 1603, 1495, 1436,
1384, 1243, 1173, 747, 693 cmꢀ1. 1H NMR (500 MHz, CDCl3) δ 2.38
(s, 3H, CH3), 2.76 (ddm, J = 16.5, 8.0 Hz, 1H, H-4 or H-8), 2.95 (ddm,
J = 16.5, 8.5 Hz, 1H, H-4 or H-8), 3.04 (dm, J = 16.5 Hz, 1H, H-4 or H-8),
3.18 (dm, J = 16.5 Hz, 1H, H-4 or H-8), 3.46 (td, J = 8.5, 3.0 Hz, 1H, H-4a
or H-7a), 3.53 (td, J = 8.5, 3.0 Hz, 1H, H-7a or H-4a), 3.78 (m, 2H,
5-Formyl-1,3-diphenyl-4,5,6,7-tetrahydro-1H-benzo[d]imida-
zol-2(3H)-one (19b). Following the method for preparation of 19a, a
mixture of 8a (0.100 g, 0.38 mmol), 18b (0.064 g, 1.14 mmol), and
BF3 Et2O (0.010 g, 0.07 mmol) in anhydrous CH2Cl2 (20 mL) was
3
stirred at ꢀ78 °C under N2 for 5 min to give 19b (0.113 g, 93%) as a pale
yellow oil. Rf 0.15 (hexane/EtOAc, 7:3). IR (film) 2929, 1702, 1663,
1
1597, 1498, 1406, 1265, 759, 734, 694 cmꢀ1. H NMR (300 MHz,
CDCl3) δ 1.80ꢀ1.96 (m, 1H, H-6), 2.15ꢀ2.26 (m, 1H, H-6),
2.40ꢀ2.48 (m, 2H, H-7), 2.55 (dm, J = 15.6 Hz, 1H, H-4), 2.62ꢀ2.80
(m, 2H, H-4, H-5), 7.26ꢀ7.49 (m, 10H, ArH), 9.71 (s, 1H, CHO). 13C
NMR (75.4 MHz, CDCl3) δ 19.9 (C-7), 20.8 (C-4), 22.1 (C-6), 46.0
(C-5), 115.7 (C-7a), 117.3 (C-3a), 126.1 (ArH), 126.2 (ArH), 127.1
(ArH), 127.2 (ArH), 129.0 (ArH), 129.1 (ArH), 134.7 (Ar), 134.8 (Ar),
152.0 (C-2), 202.3 (CHO). MS (70 eV) m/z 318 (M+, 63), 290 (15),
287 (19), 261 (28), 249 (100), 170 (10), 130 (6), 105 (13), 77 (14).
HRMS (EI) m/z [M+] calcd for C20H18N2O2: 318.1368. Found:
318.1366.
5-Acetyl-1,3-diphenyl-1H-benzo[d]imidazol-2(3H)-one
(10a). A mixture of 19a (0.070 g, 0.21 mmol) and DDQ (0.095 g, 0.42
mmol) in anhydrous CH2Cl2 (15 mL) was stirred at 20 °C under N2 for
24 h. The mixture was filtered through column chromatography packed
with Celite (3 g) on top of silica gel (5 g) (CH2Cl2). The solvent was
removed under vacuum, and the crude was purified by column chro-
matography over silica gel (20 g/g crude, hexane/EtOAc, 95:5) to give
10a (0.048 g, 70%) as a white solid. Rf 0.48 (hexane/EtOAc, 7:3); mp
170ꢀ171 °C. IR (KBr) 1718, 1675, 1587, 1496, 1448, 1389, 1255, 743,
695, 654 cmꢀ1. 1H NMR (500 MHz, CDCl3) δ 2.59 (s, 3H, CH3CO),
7.16 (dd, J = 8.0, 0.5 Hz, 1H, H-7), 7.43ꢀ7.49 (m, 2H, Ph-H),
7.50ꢀ7.62 (m, 8H, Ph-H), 7.75 (dd, J = 2.0, 0.5 Hz, 1H, H-4), 7.77
(dd, J = 8.0, 2.0 Hz, 1H, H-6). 13C NMR (125 MHz, CDCl3) δ 26.5
(COCH3), 108.2 (C-7), 108.6 (C-4), 124.0 (C-6), 126.1 (ArH), 126.2
(ArH), 128.2 (ArH), 128.3 (ArH), 129.7 (ArH), 129.8 (ArH), 129.9
(Ar), 131.9 (Ar), 133.4 (C-5), 133.8 (C-3a or C-7a), 133.9 (C-7a or
C-3a), 152.6 (C-2), 196.8 (COCH3). MS (70 eV) m/z 328 (M+, 46),
313 (66), 285 (26), 256 (38), 179 (38), 166 (32), 154 (20), 77 (100), 51
(33). HRMS (EI) m/z [M+] calcd for C21H16N2O2: 328.1212. Found:
328.1232.
5-Formyl-1,3-diphenyl-1H-benzo[d]imidazol-2(3H)-one
(10b). Following the method for preparation of 10a, a mixture of 19b
(0.100 g, 0.31 mmol) and DDQ (0.149 g, 0.66 mmol) in anhydrous
CH2Cl2 (15 mL) was stirred at 20 °C under N2 for 12 h to give 10b
(0.091 g, 92%) as a pale yellow solid. Rf 0.35 (hexane/EtOAc, 7:3); mp
186ꢀ187 °C. IR (KBr) 1726, 1689, 1593, 1498, 1466, 1393, 1254, 1175,
759, 694 cmꢀ1. 1H NMR (500 MHz, CDCl3) δ 7.24 (d, J = 8.0 Hz, 1H,
H-7), 7.45ꢀ7.51 (m, 2H, Ph-H), 7.56ꢀ7.62 (m, 8H, Ph-H), 7.65 (dd,
J = 8.0, 1.5 Hz, 1H, H-6), 7.67 (br s, 1H, H-4), 9.92 (s, 1H, CHO). 13C
NMR (125 MHz, CDCl3) δ 108.4 (C-4), 108.7 (C-7), 126.1 (ArH),
126.2 (ArH), 126.8 (C-6), 128.3 (ArH), 128.5 (ArH), 129.7 (ArH),
129.8 (ArH), 130.3 (Ar), 131.4 (C-5), 133.71 (Ar or C-7a), 133.75 (Ar
or C-3a), 134.7 (Ar), 152.5 (C-2), 191.0 (CHO). HRMS (EI) m/z [M+]
calcd for C20H14N2O2: 314.1055. Found: 314.1057.
CH2N), 3.97 (t, J = 6.0 Hz, 2H, CH2Cl), 7.05ꢀ7.48 (m, 9H, ArꢀH). 13
C
NMR (125 MHz, CDCl3) δ 19.5 (CH2), 19.7 (CH2), 21.3 (CH3), 38.5
(CH), 38.8 (CH), 42.4 (CH2N), 43.3 (CH2Cl), 114.2 (C-3a or C-8a),
115.4 (C-8a or C-3a), 123.1 (ArH), 126.2 (ArH), 126.8 (ArH), 128.3
(ArH), 128.8 (ArH), 129.1 (ArH), 129.2 (ArH), 131.7 (Ar), 134.1 (Ar),
139.4 (Ar), 152.6 (C-2), 177.7 (CO), 177.8 (CO). MS (70 eV) m/z 436
(M+, 4), 279 (18), 251 (56), 223 (79), 208 (89), 182 (90), 181 (95), 180
(100), 167 (98), 146 (50), 91 (98), 77 (35), 65 (30). HRMS (EI) m/z
[M+] calcd for C24H22ClN3O3: 435.1350. Found: 435.1350.
1,3,6-Triphenyl-4,4a,7a,8-tetrahydroimidazo[4,5-f]isoindole-
2,5,7(1H,3H,6H)-trione (17b). A mixture of 8a (0.050 g, 0.19 mmol)
and 16 (0.036 g, 0.20 mmol) in anhydrous CH2Cl2 (20 mL) was stirred
at 0 °C under N2 for 1 h. The mixture was diluted with CH2Cl2 (15 mL)
and poured into H2O (10 mL). The organic layer was washed with a 5%
aqueous solution of NaHCO3 (2 ꢁ 5 mL) with a 5% aqueous solution of
NH4Cl (2 ꢁ 15 mL) and dried (Na2SO4). The solvent was removed
under vacuum, and the crude was purified by column chromatography
over silica gel (20 g, hexane/EtOAc, 8:2) to give 17b (0.075 g, 90%) as a
white solid. Rf 0.20 (hexane/EtOAc, 7:3); mp 128ꢀ129 °C. IR (KBr)
1
1709, 1672, 1597, 1498, 1411, 1379, 1194, 759, 693 cmꢀ1. H NMR
(500 MHz, CDCl3) δ 2.83 (dm, J = 16.0 Hz, 2H, H-4, H-8), 3.12 (d, J =
16.0 Hz, 2H, H-4, H-8), 3.46ꢀ3.55 (m, 2H, H-3a, H-8a), 7.25ꢀ7.54 (m,
10H, ArH). 13C NMR (125 MHz, CDCl3) δ 20.1 (C-4, C-8), 38.8 (C-
4a, C-7a), 115.3 (C-3a, C-8a), 126.2 (ArH), 127.5 (ArH), 128.8 (ArH),
129.3 (ArH), 129.4 (ArH), 131.7 (Ar), 134.4 (Ar), 152.2 (C-2), 177.8
(C-5, C-7). HRMS (EI) m/z [M+] calcd for C27H21N3O3: 435.1583.
Found: 435.1582.
5-Acetyl-1,3-diphenyl-4,5,6,7-tetrahydro-1H-benzo[d]imi-
dazol-2(3H)-one (19a). A mixture of 8a (0.060 g, 0.23 mmol) and
18a (0.050 g, 0.71 mmol) in anhydrous CH2Cl2 (20 mL) was stirred at
ꢀ78 °C under N2, and BF3 Et2O (0.0065 g, 0.046 mmol) was added
3
dropwise. The mixture was stirred for 25 min, diluted with CH2Cl2
(15 mL), and poured into H2O (10 mL). The organic layer was washed
with a 5% aqueous solution of NaHCO3 (2 ꢁ 5 mL) and a 5% aqueous
solution of NH4Cl (2 ꢁ 15 mL) and dried (Na2SO4). The solvent was
removed under vacuum, and the crude was purified by column chro-
matography oversilica gel (20g, hexane/EtOAc, 8:2) togive19a (0.072 g,
95%) as a white solid. Rf 0.17 (hexane/EtOAc, 7:3); mp 110ꢀ112 °C. IR
(KBr) 2920, 1712, 1532, 1520, 1332, 1251, 1212, 1171, 841, 815, 760,
5-Acetyl-1-(4-chlorophenyl)-3-phenyl-4,5,6,7-tetrahy-
dro-1H-benzo[d]imidazol-2(3H)-one (19c) and 6-Acetyl-
1-(4-chlorophenyl)-3-phenyl-4,5,6,7-tetrahydro-1H-benzo-
[d]imidazol-2(3H)-one (20). Following the method for preparation
1
751 cmꢀ1. H NMR (300 MHz, CDCl3) δ 1.73ꢀ1.85 (m, 1H, H-6),
7909
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The Journal of Organic Chemistry
ARTICLE
of 19a, a mixture of 9b (0.100 g, 0.34 mmol), 18a (0.07 g, 1.0 mmol), and
Ferreira, M. L.; Brocksom, T. J. J. Braz. Chem. Soc. 2001, 12, 597. (h)
Kumar, A. Chem. Rev. 2001, 101, 1. (i) Tantillo, D. J.; Houk, K. N.; Jung,
M. E. J. Org. Chem. 2001, 66, 1938. (j) Ayers, P. W.; Morell, C.; De Prott,
F.; Geerlings, P. Chem.—Eur. J. 2007, 13, 8240. (k) Domingo, L. R.;
Sꢀaez, J. A. Org. Biomol. Chem. 2009, 7, 3576. (l) Wang, Z.; Hirschi, J. S.;
Singleton, D. A. Angew. Chem., Int. Ed. Engl. 2009, 48, 9156.
BF3 Et2O (0.0095 g, 0.067 mmol) in anhydrous CH2Cl2 (20 mL),
3
stirring at ꢀ78 °C for 5 min, gave a mixture of 19c/20 (65:35) (0.113 g,
92%) as a white solid. Rf 0.18 (hexane/EtOAc, 7:3); mp 105ꢀ110 °C. IR
(KBr) 2928, 1706, 1688, 1597, 1495, 1402, 1168, 1091, 1013, 837, 767,
1
695 cmꢀ1. H NMR (500 MHz, CDCl3) δ 1.77ꢀ1.86 (m, 1H, H-6),
(2) For representative examples on theoretical studies of DielsꢀAlder
reactions, see: (a) Gleiter, R.; B€ohm, M. C. Pure Appl. Chem. 1983,
55, 237. (b) Ginsburg, D. Tetrahedron 1983, 39, 2095. (c) Houk, K. N.; Li,
Y.; Evanseck, J. D. Angew. Chem., Int. Ed. Engl. 1992, 31, 682. (d)
Singleton, D. A. J. Am. Chem. Soc. 1992, 114, 6563. (e) Sustmann, R.;
Sicking, W. J. Am. Chem. Soc. 1996, 118, 12562. (f) García, J. I.; Mayoral,
J. A.; Salvatella, L. Tetrahedron 1997, 53, 6057. (g) Xidos, J. D.; Poirier,
R. A.; Pye, C. C.; Burnell, D. J. J. Org. Chem. 1998, 63, 105. (h) García, J. I.;
Martínez-Merino, V.; Mayoral, J. A.; Salvatella, L. J. Am. Chem. Soc. 1998,
120, 2415. (i) Imade, M.; Hirao, H.; Omoto, K.; Fujimoto, H. J. Org.
Chem. 1999, 64, 6697. (j) Kong, S.; Evanseck, J. D. J. Am. Chem. Soc. 2000,
122, 10418. (k) Quadrelli, P.; Romano, S.; Toma, L.; Caramella, P. J. Org.
Chem. 2003, 68, 6035. (l) Domingo, L. R.; Aurell, M. J.; Arnꢀo, M.; Sꢀaez,
2.19ꢀ2.24 (m, 1H, H-6), 2.22 (s, 3H, CH3CO), 2.39ꢀ2.55 (m, 3H,
H-4, 2H-7), 2.62ꢀ2.69 (m, 1H, H-4), 2.79ꢀ2.85 (m, 1H, H-5),
7.31ꢀ7.47 (m, 9H, ArH). Signals attributed to the minor isomer 20:
2.21 (s, CH3CO). 13C NMR (75.4 MHz, CDCl3) δ 20.9, 22.9, 24.8,
28.1, 47.3, 115.8, 116.7, 126.2 (ArH), 127.3 (ArH), 127.4 (ArH), 129.1
(ArH), 129.3 (ArH), 132.8 (Ar), 133.5 (Ar), 134.9 (Ar), 152.0 (C-2),
209.0 (COCH3). Signals attributed to the minor isomer 20: 20.8, 28.2,
47.2, 116.6, 117.4, 126.3 (ArH), 127.2 (ArH), 129.3 (ArH), 132.7 (Ar),
133.6 (Ar), 134.7 (Ar), 209.1 (COCH3). MS (70 eV): m/z 367 (M+,
11), 348 (15), 322 (34), 291 (45), 286 (86), 257 (43), 232 (24), 208
(43), 166 (50), 131 (49), 115 (80), 103 (61), 77 (100). HRMS (EI) m/z
[M+] calcd for C21H19N2O2Cl: 366.1135. Found: 366.1133.
€
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Theoretical Calculations. The ab initio HF/6-31G(d,p) and
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’ ASSOCIATED CONTENT
Supporting Information. Appendix 1, Copies of the 1H
S
b
NMR and 13C NMR spectra of all new compounds; Appendix 2,
Cartesian coordinates (B3LYP/6-31G**), energies, and lowest
vibrational frequencies (RHF/6-31G**) of the optimized geo-
metries of dienes 8a, 9a, 9h, as well as cyclopentadiene (22). This
material is available free of charge via the Internet at http://pubs.
acs.org.
’ AUTHOR INFORMATION
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Corresponding Author
*Fax: +5255-5729-6300/46211. E-mail: jtamariz@woodward.encb.
ipn.mx; jtamarizm@gmail.com
’ ACKNOWLEDGMENT
We thank Alberto V. Jerezano for his help in spectrometric
measurements and Bruce A. Larsen for reviewing the English of
the manuscript. J.T. acknowledges SIP/IPN (Grants 20080527,
20090519, 20100236, and 20110172) and CONACYT (Grants
43508Q and 83446) for financial support. R.B., P.B., and BMS
thank CONACYT for awarding them graduate scholarships and
also thank SIP/IPN (PIFI) and the Ludwig K. Hellweg Founda-
tion for scholarship complements. F.D. and J.T. are fellows of the
EDI-IPN and COFAA-IPN programs.
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