Assisted tandem catalytic cross metathesis-oxidation: In one flask from styrenes to 1,2-diketones and further to quinoxalines

Article abstract of DOI:10.1021/jo4005684

1,2-Diketones were synthesized from styrenes by combining a cross metathesis and a Ru-catalyzed alkene oxidation to an assisted tandem catalytic sequence. The synthesis relies on the use of just one metathesis precatalyst, which was in situ converted to the oxidation catalyst by addition of an alkyl hydroperoxide as a chemical trigger and oxidant. The one-flask sequence can be extended beyond 1,2-diketones to quinoxalines, by condensation of the oxidation products with ortho-phenylenediamine.

Full text of DOI:10.1021/jo4005684

Article
pubs.acs.org/joc
Assisted Tandem Catalytic Cross Metathesis−Oxidation: In One Flask
from Styrenes to 1,2-Diketones and Further to Quinoxalines
Bernd Schmidt,* Stefan Krehl, and Sylvia Hauke
Universitaet Potsdam, Institut fuer Chemie (Organische Synthesechemie), Karl-Liebknecht-Strasse 24-25, D-14476 Potsdam-Golm,
Germany
S
* Supporting Information
ABSTRACT: 1,2-Diketones were synthesized from styrenes by combin-
ing a cross metathesis and a Ru-catalyzed alkene oxidation to an assisted
tandem catalytic sequence. The synthesis relies on the use of just one
metathesis precatalyst, which was in situ converted to the oxidation
catalyst by addition of an alkyl hydroperoxide as a chemical trigger and
oxidant. The one-flask sequence can be extended beyond 1,2-diketones to
quinoxalines, by condensation of the oxidation products with ortho-
phenylenediamine.
the alkene, rather than the reaction conditions, and were
therefore intrigued by recent reports describing the oxidative
transformation of alkenes26,27 and alkynes28,29 into 1,2-
diketones, using Ru(II)-complexes such as [Ru(cymene)Cl2]2
as precatalysts and tert-butyl hydroperoxide as the oxidant.
Previously, only Pd-catalyzed oxidations of alkynes30−33 or a
sequence of Brønsted acid mediated alkyne hydration in
combination with subsequent α-oxidation34 had been described
as methods for transforming C−C multiple bonds into 1,2-
diketones. Although typical Ru-based metathesis catalysts had
to the best of our knowledge not been used as precatalysts for
these alkene or alkyne oxidations, we were optimistic that the
combination of an oxidative diketone formation with an olefin
metathesis reaction as outlined in Scheme 1 should be possible.
INTRODUCTION
■
Olefin metathesis reactions were found to be ideally suited for
incorporation in domino sequences1,2 shortly after the
discovery of stable and defined homogeneous precatalysts3−5
for this transformation. In these reaction sequences, often
referred to as ring rearrangement metathesis (RRM),6,7 two or
more olefin metathesis steps are coupled in a defined way,
leading ultimately to an alkene or cycloalkene. A completely
different class of sequential metathesis reactions is characterized
by the combination of an olefin metathesis reaction with a
subsequent nonmetathesis transformation of the newly
generated C−C double bond.8,9 These reaction sequences
have been described as “assisted tandem catalysis”, if both
transformations are catalyzed through different mechanisms,
but with just one precatalyst.10 Metathesis−nonmetathesis
sequences of this type require an organometallic conversion of
one catalytic species into another, to link the two originally
independent catalytic cycles. This organometallic conversion,
and hence the connection of the catalytic cycles, is normally
accomplished by a suitable reagent, which is added to the
reaction mixture in due course. Several reaction sequences have
been developed along these lines over the past decade, such as
metathesis−hydrogenation,11,12 metathesis−isomerization,13−15
metathesis−di-16−18 and ketohydroxylation,17,19 metathesis−
atom transfer radical addition,20,21 metathesis−aromatiza-
tion,22,23 and metathesis−allylic oxidation.24,25 The two latter
reaction sequences, recently developed in our group, rely on
the use of alkyl hydroperoxides as both a chemical trigger and
an oxidant. Most likely, the Ru-metathesis catalyst is converted
into a Ru(IV)-dioxo species, which mediates the subsequent
aromatization or allylic oxidation. We assume that the course of
the reaction is primarily governed by the substitution pattern of
Scheme 1. Concept of Assisted Tandem Catalytic
Metathesis−Nonmetathesis Transformations
Received: March 18, 2013
© XXXX American Chemical Society
A
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In this paper we describe the successful connection of a cross
metathesis reaction and the subsequent oxidative diketone
formation of the intermediate CM products, using only one
precatalyst. As 1,2-diketones play a prominent role in
heterocyclic chemistry, opportunities for extending the catalytic
sequence by condensation reactions have also been inves-
tigated. As a result, styrenes can be converted in a one-flask
fashion into quinoxalines and imidazole derivatives.
which prompted us to choose 3-methoxy styrene 3b as a test
substrate. Literature precedence for the cross or self-metathesis
of two styrenes35−37 to symmetrical or unsymmetrical
stilbenes38 is scarce compared to the plethora of successful
examples for cross metathesis reactions in general.39−42
However, the examples described so far in the literature
suggest that second generation catalysts give significantly better
conversions at lower catalyst loadings, although Noels et al.
reported a very promising GC-yield for one example with a
moderate loading of first generation catalyst A.36 Initially, we
tested this catalyst but could not observe any self-metathesis of
3b within 1.5 h and with a catalyst loading of 5 mol % at a
reaction temperature of 80 °C (Table 2, entry 1). This
RESULTS AND DISCUSSION
■
Initially we tested whether a typical Ru-carbene complex can
catalyze the oxidative conversion of a stilbene into a 1,2-
diketone under conditions similar to those published by Wan et
al. for the precatalyst [Ru(cymene)Cl2]2.26 Thus, E-stilbene
(1a) was treated with a catalytic amount of first generation
Grubbs’ catalyst (A) and an aqueous solution of tert-BuOOH as
the oxidant in a solvent system consisting of toluene,
acetonitrile, and water. Although the effective catalyst loading
in our experiment (2.5 mol % of Ru, entry 3) was similar to that
used by Wan et al. (1.0 mol % of [Ru(cymene)Cl2]2,
corresponding to 2.0 mol % of Ru, entry 1),26 we obtained a
significantly lower yield of benzil (2a). From our previous
experience with tert-BuOOH as a reagent for allylic oxidations,
we knew that uncatalyzed background reactions occur to some
extent, in particular after prolonged reaction times. For this
reason we reproduced the control experiment performed by
Wan et al. (entry 2), but with an extended reaction time of 36 h
(entry 4). Even after this time period, the substrate was found
to be completely inert to oxidation in the absence of Ru-
catalysts, and stilbene was quantitatively recovered (Table 1).
Table 2. Optimization of Conditions for the CM−Oxidation
of 3b
Table 1. Control Experiments and Comparison with Data
from the Literature
a
entry
catalyst and catalyst loading
Addition time t
yield
b
1
2
3
4
5
6
7
8
A (5.0 mol %)
B (2.5 mol %)
B (5.0 mol %)
B (2.5 mol %)
B (5.0 mol %)
B (2.5 mol %)
B (5.0 mol %)
−
−
0.8 min.
0.8 min.
5.0 min.
5.0 min.
10.0 min.
10.0 min.
10.0 min.
38%
48%
57%
55%
82%
65%
c
B (2.5 mol %)
30%
a
b
Isolated yield of 1,2-diketone 2b. No stilbene formation observed
c
after 1.5 h at 80 °C. 3,5-Di-tert-butyl-4-hydroxy toluene (BHT, 1.0
equiv) was added to the reaction mixture prior to addition of the tert-
butyl hydroperoxide.
entry
precatalyst (mol %)
t/h
yield of 2
91%
ref.
1
2
3
4
[Ru(cymene)Cl2]2 (1.0)
1
26
26
prompted us to switch to the second generation catalyst B,
which resulted in a complete conversion of 3b to 1b under
otherwise identical conditions. Even with a reduced catalyst
loading of 2.5 mol %, full conversion was observed by TLC
after 1.5 h at 80 °C. After the metathesis reaction cooled to
ambient temperature and the addition of the required
cosolvents and the additive [NBu4]I, the aqueous tert-butyl
hydroperoxide solution was added within less than 1 min.
Under these conditions, a moderate yield of 38% of 2b was
obtained with 2.5 mol % of precatalyst B (entry 2), which could
be slightly improved to 48% by increasing the amount of
catalyst to 5.0 mol % (entry 3). Under both conditions gas
evolution was observed during the addition of the oxidant,
indicating the formation of oxygen through Ru-catalyzed
decomposition of the tert-butyl hydroperoxide, which might
also explain the moderate yields. A similar observation has been
none
1
“not detected”
A (2.5)
none
1
50%
this work
this work
a
36
<1%
a
Stilbene (1a) was recovered in 99% yield.
From the initial test experiment with first generation Grubbs’
catalyst (A) it became evident that Ru carbenes should in
principle be suitable catalysts for this nonmetathesis trans-
formation, but that there is still a considerable activity gap
between A and the dimeric Ru-cymene complex used by Wan
et al. Therefore, we thought that the development of an assisted
tandem catalytic CM−oxidation sequence as outlined in
Scheme 1 should be promising, but that in particular the
second step would require optimization. It turned out that the
cross metathesis of styrene is difficult to monitor by TLC,
B
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made by us during the development of the RCM−allylic
oxidation sequence.24 In this case, we found that competing
decomposition of the oxidant is suppressed by slow addition of
the oxidant to the reaction mixture. We could indeed observe a
significant improvement by extending the addition time to 5
min. Interestingly, the yield of 2b was virtually unaffected by
the catalyst loading at this addition time (entries 4 and 5). The
best yields were obtained when the oxidant was added slowly
over a period of 10 min using a syringe pump. With this
addition time, a higher catalyst loading is clearly detrimental, as
the yield drops from 82% to 65% when the catalyst loading is
increased from 2.5 to 5.0 mol % (entries 6 and 7).
products with no identifiable major component. To exclude the
possibility that the complexity of the mixture was caused by
residual 4, the cross metathesis product 5 was isolated and
separately subjected to the oxidation conditions using 2.5 mol
% of Ru-carbene complex B. This experiment also resulted in
the formation of a mixture with no defined major product.
In the second experiment we used the RCM precursor 7 as a
substrate and very similar metathesis−oxidation conditions
(Scheme 3). In this case, first generation catalyst A is
Scheme 3. Attempted RCM−Oxidation of Styrenyl Ether 7
The reason for the adverse effect of a higher catalyst loading
at prolonged addition times might be a more efficient
competition of the unproductive hydroperoxide decomposition
with the intended alkene oxidation in this case. Alternatively, an
oxidative scission of the C−C σ-bond may occur as another
competing reaction. Although the expected 3-methoxy
benzaldehyde was not detected under these particular
conditions, there is ample precedence for oxidative fragmenta-
tion of alkenes to carbonyl compounds from the literature on
Ru-catalyzed dihydroxylation reactions.43−47 To test whether
radical pathways play a significant role in the oxidation step or
not, we performed a control experiment similar to that used by
Murahashi et al. for investigating the mechanism of Ru-
catalyzed allylic and benzylic oxidation48 (entry 8). Adding 1
equiv of the radical scavenger BHT immediately before
addition of the hydroperoxide leads to a decreased yield of
30%, but not to a complete inhibition of the second step. We
conclude from this observation that a mechanism proceeding
exclusively or predominantly via a radical pathway is unlikely,
but that the oxidation catalyst is intercepted to a considerable
extent by the radical scavenger.
As outlined in the introduction, we have previously
developed other oxidative metathesis sequences under different
conditions but by using hydroperoxides as a chemical trigger
and as an oxidizing agent.23,24 In these cases, the substrates
contained allylic hydrogen atoms and the oxidation step
proceeded via abstraction of this hydrogen, resulting in the
formation of five-membered aromatic heterocycles or lactones.
To check whether Ru-catalyzed diketone formation can
efficiently compete with allylic oxidation under the optimized
conditions, we performed two additional experiments. First,
styrene (3a) was reacted with 2 equiv of Z-2-butene-1,4-
diacetate (4) under the optimized CM−oxidation conditions
(Scheme 2). This experiment led to a quantitative conversion
of the intermediate CM product 549 to a complex mixture of
sufficiently active to promote the RCM and was therefore
used instead of B. Under metathesis−oxidation conditions, a
defined product could be isolated from the reaction mixture in
53% yield, which was discovered to be coumarin (8) rather
than the diketone 9. The strong preference for the allylic
oxidation reaction under the conditions of the metathesis−
oxidation sequence is somewhat surprising, as Wan et al.26
could successfully convert alkenes with allylic hydrogen atoms
into the corresponding diketones in high yields, using
[Ru(cymene)Cl2]2 as the precatalyst. We also checked whether
the preference for allylic oxidation was caused by the choice of
catalyst and repeated the metathesis−oxidation sequence for
substrate 7 with second generation catalyst B under otherwise
identical conditions. The outcome was very similar, with a yield
of 35% of 8 and no indication for the formation of any diketone
9.
Having identified this obvious limitation of the cross
metathesis−oxidation sequence, we tested the optimized
conditions for a variety of other styrenes (Table 3).
High yields of the corresponding diketones 2a−c were
obtained with styrene (3a) and its 3-methoxy- (3b) and 3-
methyl- (3c) derivatives (entries 1−3). A significantly lower
yield and a comparatively sluggish reaction was observed with
the benzyl ether 3d (entry 4), which is most likely caused by a
competing benzylic oxidation. Successful CM−oxidations could
also be accomplished for the para-substituted styrenes 3e−h,
although the isolated yields are generally lower than those for
the analogous meta-substituted styrenes. While the isolated
yield of m-methyl derivative 2e (entry 5) is comparable to that
of unsubstituted 2a, a more strongly electron-donating
substituent such as 4-methoxy (entry 6) or isopropyl (entry
8) leads to a significantly decreased isolated yield. Monitoring
the reaction by TLC revealed nearly complete consumption of
the intermediate stilbene and high selectivity; thus, the rather
low yields must most likely be attributed to loss of material
upon chromatography on silica. In the case of 4-chlorostyrene
3g the NMR spectra of the reaction mixture suggested that the
desired diketone 2g was formed to a considerable extent, but it
Scheme 2. Attempted CM−Oxidation Sequence with 2-
Butene-1,4-diacetate (4)
C
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methoxy substituted product 2f was formed in very minor
quantities and could not be isolated (Scheme 4). This
Table 3. Scope and Limitations of the Assisted Tandem
Catalytic CM−Oxidation Sequence
Scheme 4. Unsymmetrical Tandem CM−Oxidation
Sequence
a
entry
3
R1
R2
2
yield
1
3a
3b
3c
3d
3e
3f
-H
-OMe
-Me
-OBn
-H
-H
-H
2a
2b
2c
2d
2e
2f
75%
82%
81%
40%
67%
44%
2
3
-H
4
-H
5
-Me
6
-H
-OMe
-Cl
b
7
3g
3h
3i
-H
2g
2h
2i
n. d.
46%
observation suggests that the selectivity of the cross metathesis
step is much lower than expected on the basis of the literature
reports. The complete absence of 2f most likely results from
the lower reactivity of the 4,4′-dimethoxy stilbene (1f)
compared to its dimethyl analogue 1e, which becomes evident
from a comparison of the yields obtained for the symmetrical
diketones 2e and 2f via self-metathesis−oxidation of 3e and 3f
(Table 3, entries 5, 6) respectively. To investigate whether the
ratio of diketones obtained through CM−oxidation of 3e and
3f reflects the selectivity of the cross metathesis or the different
reactivity of the stilbenes in the oxidation step, we monitored
the cross metathesis reaction by GC-MS. The CM products
were formed in a statistical ratio of 1:2:1, with the
unsymmetrical stilbene resulting from cross metathesis of 3e
and 3f accounting for 50% of the mixture. We conclude from
this result that the isolated yields of CM−oxidation products
2ef (35%), 2e (22%), and 2f (<5%) indeed mirror the lower
reactivity of electron-rich C−C double bonds in the oxidative
diketone formation.
To functionalize the 1,2-diketones obtained from the CM−
oxidation sequence further, we considered an extension of the
one-flask sequence by a condensation step with 1,2-diamines,
e.g. phenylene diamine (10). The resulting products are 2,3-
diaryl quinoxalines 11, which have attracted attention for a
manifold of applications, such as dyes (e.g., for dye-sensitized
solar cells),55−57 drugs (e.g., the antihypertensive brimonidine58
or potential influenza NS1A protein inhibitors59), and organic
semiconductors.60,61 The established method for the synthesis
of 2,3-diaryl quinoxalines is the condensation of phenylene
diamines and benzil or substituted derivatives in glacial acetic
acid.56,59,62 Alternatively, catalytic amounts of Lewis acids such
as ceric ammonium nitrate have been used in water as a
solvent.63 Recently, an organocatalytic one-flask synthesis of
2,3-diaryl quinoxalines from benzaldehydes via benzoin
condensation, oxidation, and condensation with diamines has
been described.64 One of the most important tasks in the
development of tandem or one-flask sequences is to avoid using
an excess of reagents in all steps, because these will accumulate
as impurities and cause serious problems in the isolation of the
final product. Another important requirement is to ensure the
compatibility of all reaction steps with the solvent or solvent
mixture used in the previous steps. If this is not the case,
solvents have to be evaporated in between and the reaction
mixture has to be redissolved prior to the last steps of the
sequence. This procedure is inconvenient and limits the
8
-H
-iso-Pr
-CO2Me
-Ph
c
9
-H
−
c
10
11
12
13
3j
-H
2j
−
c
3k
3l
-CH=CH-CH=CH-
2k
2l
−
c
-NO2
-H
-H
−
c
3m
-NO2
2m
−
a
b
Isolated yields of diketones 2. Inseparable mixture of products.
c
Precipitate formed after completed CM step; no conversion to
diketones 2 under standard conditions.
could not be purified by chromatography or crystallization
(entry 7). When we applied the optimized CM−oxidation
conditions to styrenes 3i−m (entries 9−13), we encountered
an unexpected difficulty: after completion of the cross
metathesis step a precipitate was formed which could not be
dissolved by the addition of more toluene or acetonitrile, the
cosolvent required for the second step of the sequence. For
each styrene 3i−m the reaction mixtures were therefore
evaporated after the cross metathesis step and analyzed by
NMR spectroscopy. In all cases the precipitates were found to
be only sparingly soluble in all solvents commonly used for
NMR spectroscopy, such as CDCl3, C6D6, acetone-d6,
methanol-d4, or DMSO-d6. Although solubility problems are
sometimes observed for compounds with aromatic substituents,
this observation was surprising in these cases, because the
expected stilbenes 1i−m had previously been synthesized via
other methods, and NMR spectroscopical data were reported in
either CDCl3 or C6D6 for all of them (e.g., 1i,50 1j,51 1k,52 1l,53
1m ). The H NMR spectra obtained by us from the cross
metathesis reaction mixtures suggested that the expected
stilbenes were formed only to a very small extent, along with
minor amounts of other unidentified low-molecular weight
products and unreacted starting materials. This result points at
a polymerization of styrenes 3i−m under the cross metathesis
conditions, presumably through a radical pathway. The
sensitivity toward polymerization might be enhanced in these
cases because the C−C double bond is connected to electron-
deficient aryl substituents or extended π-systems, leading to a
better stabilization of a benzylic radical.
54
1
Encouraged by previous reports describing a remarkable
selectivity in the cross metathesis reactions of differently
substituted styrenes,36,37 we applied the tandem CM−oxidation
conditions to an equimolar mixture of para-substituted styrenes
3e and 3f. We could only isolate 35% of the desired
unsymmetrical 1,2-diketone 2ef, along with 22% of 2e. The
D
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synthetic utility of a one-flask reaction. For these reasons we
started this investigation by testing the solvent mixture from the
CM−oxidation sequence for the condensation of equimolar
amounts of benzil (2a) and phenylene diamine (10). Under
standard conditions, i.e. by heating a 1:1 mixture of 2a and 10
in acetic acid at 60 °C, the desired 2,3-diphenyl quinoxaline
(11a) was obtained in 75% yield at an initial substrate
concentration of 0.5 M after 2 h. We then simulated the final
step of the projected CM−oxidation−condensation sequence
by dissolving equimolar amounts of 2a and 10 in a mixture of
toluene, acetonitrile, and water. Glacial acetic acid was added to
this mixture as an additional cosolvent, resulting in an overall
initial substrate concentration of 0.12 M, and the reaction
mixture was again heated to 60 °C for 2 h. Gratifyingly, the
yield of quinoxaline 11a was even higher under these simulated
one-flask conditions compared to the standard conditions using
glacial acetic acid as a solvent (Scheme 5).
Notably, the isolated yields of the quinoxalines 11d and 11h
were considerably higher than those of the underlying 1,2-
diketones 2d and 2h. Another remarkable example is the 4-
chloro derivative 11g, which could be isolated in 47% yield, in
contrast to the corresponding 1,2-diketone 2g, which was
obtained as an inseparable mixture. This example illustrates that
sometimes extending a one-flask sequence by additional steps
does not complicate, but facilitates, the isolation of the final
product. This might explain why the isolated yields of
quinoxalines 11d−h are higher than expected considering the
isolated yields of the 1,2-diketones reported in Table 3
(Scheme 6 and Table 4).
Table 4. Quinoxalines via One-Flask CM−Oxidation−
Condensation (see Scheme 6 for details)
a
entry
3
R1
-H
R2
-H
11
yield
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
11a
11b
11c
11d
11e
11f
45%
51%
47%
54%
45%
44%
47%
51%
-OMe
-Me
-OBn
-H
-H
Scheme 5. Condensation of 2a and 10 under Simulated One-
Flask Conditions
-H
-H
-Me
-OMe
-Cl
-H
3g
3h
-H
11g
11h
-H
-iso-Pr
a
Isolated yields of quinoxalines 11.
To further evaluate the opportunities for extending the CM−
oxidation sequence by other condensation steps, we inves-
tigated a synthesis of spirocyclic bisimines 14. For example, 14a
had previously been synthesized from benzil (2a), cyclo-
hexanone (12), and NH4OAc (13) in acetic acid. The
spirocycle 14a served as a precursor for enantiomerically pure
C2-symmetric 1,2-diamines, which were used as chiral ligands
for Lewis acidic catalysts, e.g. for Diels−Alder reactions.65
Similar to the optimization of conditions for the one-flask
quinoxaline synthesis, we compared the condensation of benzil
(2a), cyclohexanone (12), and NH4OAc (13) in acetic acid
under the published conditions65 with the conditions given by
the tandem protocol (Scheme 7). In contrast to the
condensation of benzil and phenylenediamine, the condensa-
tion leading to 14a is less tolerant toward the modified solvent
system. If acetic acid is replaced by a mixture of toluene,
acetonitrile, water, and acetic acid, the reaction becomes
With this promising result in hand, we repeated the CM−
oxidation reaction for styrene (3a) and extended the sequence,
simply by adding 1 equiv of phenylene diamine (10) and acetic
acid as a cosolvent and heating the mixture to 60 °C for
another 2 h. 2,3-Diphenyl quinoxaline (11a) was obtained
following this protocol in 45% yield, which corresponds to an
average yield of 67% per step, whereas the average yield for the
two-step protocol is 78%. This difference does not indicate an
adverse effect of the Ru-catalyst on the condensation step but is
more likely caused by the necessity to remove Ru-residues from
the reaction mixtures.
Similarly, substituted 2,3-diarylquinoxalines 11b−h were
isolated in comparable yields starting from styrenes 3b−h.
Scheme 6. From Styrenes 3 to Quinoxalines 11 via One-Flask CM−Oxidation−Condensation
E
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bisimines is significantly less effective and provides the products
only in moderate yields after an intermediate exchange of
solvents. The potential of the sequence, in particular for the
synthesis of polyarylated quinoxalines with interesting optical
and electronical properties, will be the subject of future
investigations.
Scheme 7. Condensation of 2a, 12, and NH4OAc under
Simulated One-Flask Conditions
EXPERIMENTAL SECTION
■
General Methods. All experiments were conducted in dry reaction
vessels under an atmosphere of dry nitrogen. Solvents were purified by
1
standard procedures. H NMR spectra were obtained at 300 MHz in
CDCl3 with tetramethylsilane (δ = 0.00 ppm) as an internal standard.
Coupling constants (J) are given in Hz. 13C NMR spectra were
recorded at 75 MHz in CDCl3 with CDCl3 (δ = 77.0 ppm) as an
internal standard. The number of coupled protons was analyzed by
APT-experiments and is denoted by a number in parentheses
following the chemical shift value. IR spectra were recorded as neat
films on NaCl or KBr plates or as KBr discs. Wavenumbers (ν) are
given in cm−1. The peak intensities are defined as strong (s), medium
(m), or weak (w). Low and high resolution mass spectra were
obtained by EI/TOF.
considerably slower and remains incomplete even after 8 h. The
isolated yield of 14a from this experiment was 56%, compared
to 84% obtained under standard conditions in neat acetic acid
within 1.5 h.
General Procedure for the Synthesis of 1,2-Diketones 2
from Styrenes 3. To a solution of the appropriate styrene 3 (1.0
mmol) in toluene (3.0 mL) was added Ru-catalyst B (20.6 mg, 2.5 mol
%). The solution was stirred for 1.5 h at 80 °C. After cooling to
ambient temperature, acetonitrile (3.0 mL), water (0.6 mL), and
tetrabutylammonium iodide (55 mg, 0.15 mmol) were added. Then
tert-butyl hydroperoxide (70 wt % in water, 500 μL, 1.8 mmol) was
added dropwise via a syringe pump within 10 min. After stirring for 1.0
h at ambient temperature the solution was diluted with methyl tert-
butyl ether (75 mL) and washed with a saturated aqueous solution of
Na2SO3 (5 mL). After phase separation the organic layer was dried
with MgSO4 and filtered, and all volatiles were removed in vacuo. The
residue was purified by column chromatography.
This rather slow reaction and the decreased isolated yield
prompted us to modify the conditions for the one-flask
synthesis of spirocycles 14 from styrenes 3 by evaporating the
solvent mixture after the CM−oxidation step and redissolving
the residue in acetic acid prior to the addition of cyclohexanone
and NH4OAc (Scheme 8). While 14a could be synthesized
Scheme 8. From Styrenes 3 to Spirodiimines 14 via One-
Flask CM−Oxidation−Condensation
Benzil (2a).66 Following the general procedure, 2a was obtained
from 3a (104 mg, 1.0 mmol) as a yellowish solid (79 mg, 0.38 mmol,
75%). Mp 78−80 °C; 1H NMR (300 MHz, CDCl3) δ 7.94−7.87
(4H), 7.63−7.54 (2H), 7.49−7.40 (4H); 13C NMR (75 MHz, CDCl3)
δ 194.5 (0), 134.9 (1), 133.0 (0), 129.9 (1), 129.0 (1); IR (KBr-disc) ν
3065 (w), 1616 (s), 1594 (m), 1580 (w), 1451 (m), 1326 (w); HRMS
(EI) calcd for C14H10O2 [M]+: 210.0681, found: 210.0699; MS (EI)
m/z 210 (M+, 3), 105 (100), 77 (48), 51 (18), 43 (8).
1,2-Bis(3-methoxyphenyl)ethane-1,2-dione (2b).67 Following
the general procedure, 2b was obtained from 3b (134 mg, 1.0 mmol)
1
as a yellowish solid (110 mg, 0.41 mmol, 82%). Mp 80−82 °C; H
NMR (300 MHz, CDCl3) δ 7.54 (dd, 2H, J = 2.4, 1.6), 7.47 (ddd, 2H,
J = 7.6, 1.2, 1.2), 7.39 (dd, 2H, J = 7.9, 7.7), 7.20 (ddd, 2H, J = 8.0, 2.6,
1.0), 3.86 (s, 6H); 13C NMR (75 MHz, CDCl3) δ 194.3 (0), 160.1
(0), 134.3 (0), 130.0 (1), 123.1 (1), 121.8 (1), 112.9 (1), 55.5 (3); IR
(KBr-disc) ν 2918 (m), 2850 (w), 1720 (m), 1670 (m), 1596 (m),
1582 (m), 1486 (s), 1432 (m), 1259 (s); HRMS (EI) calcd for
C16H14O4 [M]+: 270.0892, found: 270.0888; MS (EI) m/z 270 (M+,
8), 135 (100), 107 (20), 92 (14), 77 (16).
from styrene via this protocol in a fair yield of 50%, two further
examples, starting from methyl substituted styrenes 3c and 3e,
gave the corresponding spirocycles 14c and 14e, respectively,
only in a significantly lower yield of ca. 30%.
CONCLUSIONS
■
In summary, we demonstrated that the Ru-catalyzed cross
metathesis of styrenes and the Ru-catalyzed oxidation of the
intermediate stilbenes to 1,2-diketones can be coupled in an
assisted tandem catalytic transformation, using the oxidant
required for the second step as a chemical trigger to convert the
metathesis active carbene into an oxidation catalyst, presumably
a Ru-dioxo-species. The sequence does not require the removal
of solvents or byproducts in the first step before the second
step is initiated. Instead, the addition of appropriate cosolvents
after completion of the first catalytic step, together with the
oxidant, is sufficient. The CM−oxidation sequence can be
extended by an uncatalyzed condensation step under one-flask
conditions. While the reaction with phenylene diamine
produces quinoxalines efficiently without a solvent exchange,
the three-component condensation leading to spirocyclic
1,2-Di-m-tolylethane-1,2-dione (2c).68 Following the general
procedure, 2c was obtained from 3c (118 mg, 1.0 mmol) as a
1
yellowish solid (96 mg, 0.41 mmol, 81%). Mp 90−92 °C; H NMR
(300 MHz, CDCl3) δ 7.80 (s (br), 2H), 7.79 (d, 2H, J = 8.1), 7.49 (d,
2H, J = 7.5), 7.41 (dd, J = 7.6, 7.5), 2.42 (s, 6H); 13C NMR (75 MHz,
CDCl3) δ 194.9 (0), 139.0 (0), 135.7 (1), 133.1 (0), 130.2 (1), 128.9
(1), 127.2 (1), 21.2 (3); IR (KBr-disc) ν 3030 (w), 2923 (w), 1669
(s), 1603 (m), 1584 (m), 1452 (w); HRMS (EI) calcd for C16H14O2
[M]+: 238.0994, found: 238.0978; MS (EI) m/z 238 (M+, 10), 136
(20), 119 (78), 91 (35), 85 (80), 83 (100), 71 (19), 57 (22), 47 (24),
43 (27).
1,2-Bis(3-(benzyloxy)phenyl)ethane-1,2-dione (2d). Follow-
ing the general procedure, 2d was obtained from 3d (210 mg, 1.0
mmol) as a yellowish solid (84 mg, 0.20 mmol, 40%). Mp 111−113
1
°C; H NMR (300 MHz, CDCl3) δ 7.60 (dd, 2H, J = 2.3, 1.5), 7.49
(ddd, 2H, J = 7.5, 2.5, 1.1) 7.48−7.34 (14H), 7.30 (ddd, 2H, J = 8.2,
F
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The Journal of Organic Chemistry
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2.6, 1.1), 5.10 (s, 4H); 13C NMR (75 MHz, CDCl3) δ 194.3 (0), 159.2
(0), 136.2 (0), 134.3 (0), 130.1 (1), 128.6 (1), 128.2 (1), 127.5 (1),
123.2 (1), 122.4 (1), 114.4 (1), 70.3 (2); IR (KBr-disc) ν 3066 (w),
3033 (w), 2921 (w), 2873 (w), 1668 (s), 1589 (s), 1483 (s), 1440 (s),
1382 (w); HRMS (EI) calcd for C28H22O4 [M]+: 422.1518, found:
422.1521; MS (EI) m/z 422 (M+, 1), 211 (40), 91 (100), 83 (52).
1,2-Di-p-tolylethane-1,2-dione (2e).68 Following the general
procedure, 2e was obtained from 3e (118 mg, 1.0 mmol) as a
yellowish solid (80 mg, 0.34 mmol, 67%). Mp 101−103 °C; 1H NMR
(300 MHz, CDCl3) δ 7.78 (d, 4H, J = 8.2), 7.22 (d, 4H, J = 7.9), 2.35
(s, 6H); 13C NMR (75 MHz, CDCl3) δ 194.5 (0), 146.0 (0), 130.7
(1), 130.0 (1), 129.7 (0), 21.2 (3); IR (KBr-disc) ν 2924 (w), 1667
(s), 1602 (m), 1584 (m), 1484 (w), 1451 (w); HRMS (EI) calcd for
C16H14O2 [M]+: 238.0994, found: 238.0984; MS (EI) m/z 238 (M+,
1), 119 (100), 91 (46), 65 (32), 39 (20).
2,3-Diphenylquinoxaline (11a).71 Following the general proce-
dure, 11a was obtained from 3a (104 mg, 1.0 mmol) as a yellowish
solid (64 mg, 0.23 mmol, 45%). Mp 118−120 °C; H NMR (300
MHz, CDCl3) δ 8.18 (dd, 2H, J = 6.4, 3.5), 7.75 (dd, 2H, J = 6.4, 3.5),
7.56−7.48 (4H), 7.39−7.27 (6H); 13C NMR (75 MHz, CDCl3) δ
153.4 (0), 141.2 (0), 139.1 (0), 129.8 (1), 129.2 (1), 128.7 (1), 128.2
(1); IR (KBr-disc) ν 3059 (m), 1558 (w), 1477 (m), 1442 (m), 1396
(m), 1344 (m); HRMS (EI) calcd for C20H14N2 [M]+: 282.1157
found: 282.1156; MS (EI) m/z 282 (M+, 100), 181 (65), 179 (20),
178 (18).
1
2,3-Bis(3-Methoxyphenyl)quinoxaline (11b).72 Following the
general procedure, 11b was obtained from 3b (134 mg, 1.0 mmol) as a
yellowish solid (87 mg, 0.26 mmol, 51%). Mp 108−110 °C; 1H NMR
(300 MHz, CDCl3) δ 8.20 (dd, 2H, J = 6.4, 3.5), 7.79 (dd, 2H, J = 6.4,
3.5), 7.30−7.21 (2H), 7.15−7.08 (4H), 6.93 (ddd, 2H, J = 8.2, 2.6,
0.9), 3.73 (s, 6H); 13C NMR (75 MHz, CDCl3) δ 159.5 (0), 153.2
(0), 141.2 (0), 140.3 (0), 129.9 (1), 129.3 (1), 129.2 (1), 122.3 (1),
115.2 (1), 114.8 (1), 55.2 (3); IR (KBr-disc) ν 2937 (w), 2834 (w),
1580 (s), 1489 (m), 1460 (m), 1426 (m), 1339 (m); HRMS (EI)
calcd for C22H18O2N2 [M]+: 342.1368, found: 342.1350; MS (EI) m/z
342 (M+, 100), 311 (30), 299 (18), 85 (18), 83 (27).
1,2-Bis(4-methoxyphenyl)ethane-1,2-dione (2f).68 Following
the general procedure, 2f was obtained from 3f (134 mg, 1.0 mmol) as
1
a yellowish solid (59 mg, 0.22 mmol, 44%). Mp 125−127 °C; H
NMR (300 MHz, CDCl3) δ 7.94 (d, 4H, J = 8.9), 6.97 (d, 4H, J = 9.0),
3.88 (s, 6H); 13C NMR (75 MHz, CDCl3) δ 193.4 (0), 164.8 (0),
132.2 (1), 114.3 (1), 114.3 (0), 55.6 (3); IR (KBr-disc) ν 3067 (w),
2956 (w), 2846 (w), 2654 (w), 1691 (w), 1655 (s), 1596 (s), 1572 (s),
1509 (m), 1423 (m); HRMS (EI) calcd for C16H14O4 [M]+: 270.0892,
found: 270.0904; MS (EI) m/z 270 (M+, 5), 135 (100), 107 (6), 92
(4), 77 (10).
2,3-Di-m-tolylquinoxaline (11c).73 Following the general
procedure, 11c was obtained from 3c (118 mg, 1.0 mmol) as a
yellowish solid (73 mg, 0.24 mmol, 47%). Mp 109−111 °C; 1H NMR
(300 MHz, CDCl3) δ 8.18 (dd, 2H, J = 6.4, 3.4), 7.77 (dd, 2H, J = 6.4,
3.5), 7.47−7.43 (2H), 7.19−7.15 (6H), 2.35 (s, 6H); 13C NMR (75
MHz, CDCl3) δ 153.7 (0), 141.2 (0), 139.1 (0), 138.0 (0), 130.4 (1),
129.7 (1), 129.5 (1), 129.2 (1), 127.9 (1), 127.1 (1), 21.4 (3); IR
(KBr-disc) ν 3057 (m), 2922 (w), 1719 (w), 1605 (w), 1479 (w),
1340 (s), 1276 (w); HRMS (EI) calcd for C22H18N2 [M]+: 310.1470,
found: 310.1489; MS (EI) m/z 310 (M+, 28), 195 (22), 192 (24), 165
(31), 147 (38), 116 (71), 91 (50), 90 (54), 76 (100), 65 (72), 57 (62),
50 (74).
1,2-Bis(4-isopropylphenyl)ethane-1,2-dione (2h).69 Following
the general procedure, 2h was obtained from 3h (146 mg, 1.0 mmol)
1
as a yellowish solid (68 mg, 0.23 mmol, 46%). Mp 74−76 °C; H
NMR (300 MHz, CDCl3) δ 7.91 (d, 4H, J = 8.4), 7.35 (d, 4H, J = 8.2),
2.97 (sept, 2H, J = 6.9), 1.26 (d, 12H, J = 6.9); 13C NMR (75 MHz,
CDCl3) δ 194.5 (0), 156.6 (0), 131.1 (0), 130.1 (1), 127.1 (1), 34.5
(1), 23.5 (3); IR (KBr-disc) ν 2962 (m), 2930 (w), 2872 (w), 1720
(w), 1670 (s), 1601 (s), 1460 (m); HRMS (EI) calcd for C20H22O2
[M]+: 294.1620, found: 294.1614; MS (EI) m/z 294 (M+, 4), 147
(100), 91 (10).
2,3-Bis(3-(benzyloxy)phenyl)quinoxaline (11d). Following the
general procedure, 11d was obtained from 3d (210 mg, 1.0 mmol) as a
1
yellowish solid (133 mg, 0.27 mmol, 54%). Mp 138−140 °C; H
1-(4-Methoxyphenyl)-2-p-tolylethane-1,2-dione (2ef).70 Fol-
lowing the general procedure, 2ef was obtained from 3e (59 mg, 0.5
mmol) and 3f (67 mg, 0.5 mmol) as a yellowish solid (44 mg, 0.17
mmol, 35%), along with 2e (26 mg, 0.11 mmol, 22%). Mp 103−105
°C; 1H NMR (300 MHz, CDCl3) δ 7.96 (d, 2H, J = 8.9), 7.88 (d, 2H,
J = 8.2), 7.31 (d, 2H, J = 8.0), 6.99 (d, 2H, J = 8.9), 3.89 (s, 3H), 2.44
(s, 3H); 13C NMR (75 MHz, CDCl3) δ 194.6 (0), 193.3 (0), 164.9
(0), 145.9 (0), 132.3 (1), 130.8 (0), 130.0 (1), 129.6 (1), 126.2 (0),
114.3 (1), 55.6 (3), 21.9 (3); IR (KBr-disc) ν 2936 (w), 2842 (w),
1664 (s), 1595 (s), 1573 (m), 1511 (m), 1309 (w); HRMS (EI) calcd
for C16H14O3 [M]+: 254.0943, found: 254.0937; MS (EI) m/z 254
(M+, 5), 135 (100), 119 (22), 91 (12).
NMR (300 MHz, CDCl3) δ 8.18 (dd, 2H, J = 6.4, 3.4), 7.77 (dd, 2H, J
= 6.4, 3.5), 7.41−7.21 (12H), 7.19 (dd, 2H, J = 2.2, 1.7), 7.10 (ddd,
2H, J = 7.5, 1.4, 0.8), 6.99 (ddd, 2H, J = 8.2, 2.5, 0.9), 4.94 (s, 4H); 13C
NMR (75 MHz, CDCl3) δ 158.8 (0), 153.2 (0), 141.2 (0), 140.4 (0),
136.9 (0), 130.0 (1), 129.3 (1), 129.2 (1), 128.5 (1), 127.9 (1), 127.4
(1), 122.6 (1), 116.1 (1), 116.1 (1), 70.2 (2); IR (KBr-disc) ν 3062
(w), 3033 (w), 2866 (w), 1736 (w), 1582 (m), 1487 (m), 1434 (m),
1338 (m); HRMS (EI) calcd for C34H26O2N2 [M]+: 494.1994, found:
494.1991; MS (EI) m/z 494 (M+, 28), 403 (18), 91 (100).
2,3-Di-p-tolylquinoxaline (11e).64 Following the general proce-
dure, 11e was obtained from 3e (118 mg, 1.0 mmol) as a yellowish
1
solid (70 mg, 0.23 mmol, 45%). Mp 139−145 °C; H NMR (300
Coumarin (8). Following the general procedure, 8 was obtained
from 7 (160 mg, 1.0 mmol) as a colorless solid (77 mg, 0.53 mmol,
53%), mp 70−72 °C. Analytical data are identical to those previously
reported by us.24
MHz, CDCl3) δ 8.15 (dd, 2H, J = 6.4, 3.5), 7.74 (dd, 2H, J = 6.4, 3.4),
7.43 (d, 4H, J = 8.1), 7.15 (d, 4H, J = 7.9), 2.37 (s, 6H); 13C NMR (75
MHz, CDCl3) δ 153.5 (0), 141.2 (0), 138.7 (0), 136.5 (0), 129.8 (1),
129.6 (1), 129.1 (1), 128.9 (1), 21.3 (3); IR (KBr-disc) ν 3058 (m),
3029 (m), 2976 (m), 2920 (m), 1717 (w), 1613 (w), 1342 (s); HRMS
(EI) calcd for C22H18N2 [M]+: 310.1470, found: 310.1472; MS (EI)
m/z 310 (M+, 100), 295 (46), 192 (20), 165 (16), 146 (10), 116 (9),
91 (8), 90 (7).
General Procedure for the Synthesis of Quinoxalines 11
from Styrenes 3. To a solution of the appropriate styrene 3 (1.0
mmol) in toluene (3.0 mL) was added Ru-catalyst B (20.6 mg, 2.5 mol
%). The solution was stirred for 1.5 h at 80 °C. After the solution
cooled to ambient temperature, acetonitrile (3.0 mL), water (0.6 mL),
and tetrabutylammonium iodide (55 mg, 0.15 mmol) were added.
Then tert-butyl hydroperoxide (70 wt % in water, 500 μL, 1.8 mmol)
was added dropwise via a syringe pump within 10 min. After stirring
for 1.0 h at ambient temperature, the solution was diluted with glacial
acetic acid (2 mL) and heated to 60 °C. At this temperature o-
phenylene diamine (10, 59 mg, 0.5 mmol) was added and the mixture
was stirred for an additional 2 h. After the mixture cooled to ambient
temperature, all volatiles were removed in vacuo and the residue was
treated with aqueous NaOH (1 M, 10 mL). The aqueous layer was
extracted three times with ethyl acetate (each time 20 mL). The
combined organic layers were dried with MgSO4 and filtered, and all
volatiles were removed in vacuo. The residue was purified by column
chromatography.
2,3-Bis(4-methoxyphenyl)quinoxaline (11f).64 Following the
general procedure, 11f was obtained from 3f (134 mg, 1.0 mmol) as a
yellowish solid (76 mg, 0.22 mmol, 44%). Mp 143−145 °C; 1H NMR
(300 MHz, CDCl3) δ 8.13 (dd, 2H, J = 6.4, 3.4), 7.72 (dd, 2H, J = 6.4,
3.4), 7.50 (d, 4H, J = 8.9), 6.88 (d, 4H, J = 8.8), 3.83 (s, 6H); 13C
NMR (75 MHz, CDCl3) δ 160.2 (0), 153.0 (0), 141.1 (0), 131.8 (0),
131.3 (1), 129.5 (1), 129.0 (1), 113.8 (1), 55.3 (3); IR (KBr-disc) ν
3061 (w), 2934 (w), 1836 (w), 1735 (w), 1606 (s), 1513 (s), 1460
(m); HRMS (EI) calcd for C22H18O2N2 [M]+: 342.1368, found:
342.1372; MS (EI) m/z 342 (M+, 100), 311 (22), 299 (8), 209 (7),
166 (23), 135 (16), 133 (24).
2,3-Bis(4-chlorophenyl)quinoxaline (11g).64 Following the
general procedure, 11g was obtained from 3g (138 mg, 1.0 mmol)
as a yellowish solid (83 mg, 0.24%, 47%). Mp 186−188 °C; 1H NMR
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(300 MHz, CDCl3) δ 8.15 (dd, 2H, J = 6.4, 3.4) 7.77 (dd, 2H, J = 6.4,
3.5), 7.46 (d, 4H, J = 8.5), 7.33 (dd, 4H, J = 8.6); 13C NMR (75 MHz,
CDCl3) δ 151.9 (0), 141.2 (0), 137.3 (0), 135.3 (0), 131.2 (1), 130.3
(1), 129.2 (1), 128.7 (1); IR (KBr-disc) ν 3062 (w), 1593 (m), 1556
(m), 1396 (m), 1342 (m), 1220 (m), 1090 (s); HRMS (EI) calcd for
C20H12N2[35]Cl2 [M]+: 350.0378, found: 350.0372; MS (EI) m/z 332
(M+, 68), 350 (M+, 100), 349 (100), 315 (46), 178 (42).
Anal. Calcd for C22H24N2 (316.19): C, 83.5; H, 7.6; N, 8.9. Found: C,
83.5; H, 7.8; N, 8.7.
ASSOCIATED CONTENT
■
S
* Supporting Information
1
Copies of H and 13C NMR spectra for all reaction products.
2,3-Bis(4-isopropylphenyl)quinoxaline (11h).69 Following the
general procedure, 11h was obtained from 3h (146 mg, 1.0 mmol) as a
yellowish solid (94 mg, 0.26 mmol, 51%). Mp 149−151 °C; 1H NMR
(300 MHz, CDCl3) δ 8.15 (dd, 2H, J = 6.3, 3.4), 7.71 (dd, 2H, J = 6.4,
3.4), 7.47 (d, 4H, J = 8.2), 7.19 (d, 4H, J = 8.2), 2.91 (sept, 2H, J =
6.8), 1.25 (d, 12H, J = 6.9); 13C NMR (75 MHz, CDCl3) δ 153.5 (0),
149.6 (0), 141.1 (0), 136.7 (0), 129.7 (1), 129.5 (1), 129.1 (1), 126.3
(1), 33.9 (1), 23.8 (3); IR (KBr-disc) ν 2960 (s), 1720 (w), 1609 (w),
1460 (m), 1390 (w), 1340 (m); HRMS (EI) calcd for C26H26N2 [M]+:
366.2096, found: 366.2090; MS (EI) m/z 366 (M+, 100), 351 (24),
323 (50), 281 (16), 147 (20).
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: bernd.schmidt@uni-potsdam.de.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
General Procedure for the Synthesis of Spirocyclic
Bisimines 14 from Styrenes 3. To a solution of the appropriate
styrene 3 (1.0 mmol) in toluene (3.0 mL) was added catalyst B (20.6
mg, 2.5 mol %). The solution was stirred for 1.5 h at 80 °C. After the
solution cooled to ambient temperature, acetonitrile (3.0 mL), water
(0.6 mL), and [NBu4]I (55 mg, 0.15 mmol) were added. Then tert-
butyl hydroperoxide (70 wt % in water, 500 μL, 1.8 mmol) was added
dropwise via a syringe pump within 10 min. After the solution stirred
for 1.0 h at ambient temperature, all volatiles were removed in vacuo.
The residue was dissolved in glacial acetic acid (2 mL), and
cyclohexanone (98 mg, 1.0 mmol) and NH4OAc (806 mg, 10.9
mmol) were added. The solution was heated to 100 °C for 2 h. After
the solution cooled to ambient temperature, all volatiles were removed
in vacuo and the residue was treated with aqueous NaOH (1 M, 10
mL). The aqueous layer was extracted three times with methyl tert-
butyl ether (each time 20 mL). The combined organic layers were
dried with MgSO4 and filtered, and all volatiles were removed in
vacuo. The residue was purified by column chromatography.
This work was generously supported by the Deutsche
Forschungsgemeinschaft (DFG Grant Schm1095/6-2). We
thank Evonik Oxeno for generous donations of solvents.
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2,3-Di-m-tolyl-1,4-diazaspiro[4.5]deca-1,3-diene (14c).75 Fol-
lowing the general procedure, 14c was obtained from 3c (118 mg, 1.0
mmol) as a yellowish solid (98 mg, 0.15 mmol, 31%). Mp 78−80 °C;
1H NMR (300 MHz, CDCl3) δ 7.42 (s, 2H), 7.25−7.17 (6H), 2.34 (s,
6H), 2.03−1.88 (4H), 1.88−1.66 (6H); 13C NMR (75 MHz, CDCl3)
δ 164.2 (0), 138.0 (0), 133.1 (0), 130.6 (1), 129.5 (1), 127.9 (1),
126.0 (1), 103.9 (0), 34.8 (2), 25.7 (2), 24.1 (2), 21.3 (3); IR (KBr-
disc) ν 2929 (m), 2854 (w), 1730 (w), 1606 (w), 1543 (w), 1481 (w),
1445 (w), 1283 (m); HRMS (EI) calcd for C22H24N2 [M]+: 316.1939,
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(15). Anal. Calcd for C22H24N2 (316.19): C, 83.5; H, 7.6; N, 8.9.
Found: C, 83.9; H, 7.8; N, 8.7.
2,3-Di-p-tolyl-1,4-diazaspiro[4.5]deca-1,3-diene (14e).75 Fol-
lowing the general procedure, 14e was obtained from 3e (118 mg, 1.0
mmol) as a yellowish solid (95 mg, 0.15 mmol, 30%). Mp 120−122
°C; 1H NMR (300 MHz, CDCl3) δ 7.41 (d, 4H, J = 8.1), 7.16 (d, 4H,
J = 7.9), 2.38 (s, 6H), 2.02−1.88 (4H), 1.84−1.66 (6H); 13C NMR
(75 MHz, CDCl3) δ 164.0 (0), 140.0 (0), 130.5 (0), 128.9 (1), 128.9
(1), 103.7 (0), 34.8 (2), 25.8 (2), 24.2 (2), 21.4 (3); IR (KBr-disc) ν
3028 (w), 2928 (m), 2854 (m), 1614 (w), 1550 (w), 1501 (m), 1444
(m), 1273 (m); HRMS (EI) calcd for C22H24N2 [M]+: 316.1939,
found: 316.1952; MS (EI) m/z 316 (M+, 2), 199 (100), 118 (15).
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