Micellar catalysis using a photochromic surfactant: Application to the pd-catalyzed tsuji-trost reaction in water

Article abstract of DOI:10.1021/jo401737t

The first example of a Pd-catalyzed Tsuji-Trost reaction, applied in a photochromic micellar media under conventional heating and microwave irradiation, is reported. The surfactant activity and recycling ability were investigated and compared with those of a few commercially available surfactants. The synthetic photochromic surfactant proved to be efficient, recyclable, and versatile for Pdcatalyzed coupling reactions.

Full text of DOI:10.1021/jo401737t

Article
pubs.acs.org/joc
Micellar Catalysis Using a Photochromic Surfactant: Application to
the Pd-Catalyzed Tsuji−Trost Reaction in Water
Muriel Billamboz, Floriane Mangin, Nicolas Drillaud, Carole Chevrin-Villette, Estelle Banaszak-Leonard,
́
and Christophe Len*
Universite
́
de Technologie de Compieg
̀
ne, Transformation Integ
́ ́ ̀
ree de la Matiere Renouvelable, EA 4297 UTC/ESCOM, Centre de
recherche de Royallieu, BP 20529, F-60205 Compieg
̀
ne Cedex, France
S
* Supporting Information
ABSTRACT: The first example of a Pd-catalyzed Tsuji−Trost reaction,
applied in a photochromic micellar media under conventional heating
and microwave irradiation, is reported. The surfactant activity and
recycling ability were investigated and compared with those of a few
commercially available surfactants. The synthetic photochromic
surfactant proved to be efficient, recyclable, and versatile for Pd-
catalyzed coupling reactions.
ology using conventional and microwave heating under low
loading conditions (1 mol % Pd).
INTRODUCTION
■
With the notion of green chemistry, organic chemists are
strongly encouraged to develop safer protocols. Among the 12
principles that govern green chemistry,1 organic reactions
conducted in safer solvents have received considerable
attention.2 In this context, substantial efforts have been devoted
to the development of efficient Pd-catalyzed cross-coupling
reactions in aqueous media.3
Water as a solvent has many advantages over usual organic
solvents: it is the least expensive and safest solvent that is
nonflammable, inexplosive, and nontoxic. Water has unique
properties in solvating organic molecules, leading to positive
effects on reactivities and selectivities.4 However, the potential
scope of aqueous organometallic catalysis is drastically reduced
when highly hydrophobic substrates are involved in the
chemical transformations. To overcome this problem, different
strategies have been studied: the use of organic cosolvents5 or
ionic liquids6 as well as additives, such as phase transfer agents,7
cyclodextrins,8 polymers,9 or surfactants.10
RESULTS AND DISCUSSION
■
Several photoresponsive surfactants have been reported with
different photoresponsive groups used to provide structural
change.13 The nonionic surfactant C4-Azo-PEG 1 was selected
for this study since ionic surfactants can inhibit the reaction due
to electrostatic repulsions at the micelle−water interface.14 It
possesses an azobenzene moiety as the photochromic core, a
C4 alkyl chain as a hydrophobic tail, and a polyethyleneglycol
(PEG) as a nonionic hydrophilic headgroup (Figure 1).
Figure 1. Structure of C4-Azo-PEG 1.
Recently, we have reported the synthesis and use of a novel
photochromic azobenzene-based surfactant in acetylation
reactions in water.11 This surfactant was designed to (i)
photo-organize and disorganize in aqueous solution, (ii) allow a
better extraction of the products formed due to its photo-
chromism property, (iii) facilitate the reactions taking place in
an aqueous phase, and (iv) enable the recycling of the aqueous
phase. On the basis of these factors, the concept of
photochromic surfactant for Pd-catalyzed cross-coupling
reactions in water was investigated in one of the most
important reactions for carbon−carbon bond formation, the
Tsuji−Trost reaction. Pd-catalyzed allylic substitution reactions
are widely employed for constructing C−C, C−N, C−S, and
C−O bonds with high chemo-, regio-, and stereoselectivities.12
Surprisingly, the development of the Tsuji−Trost reaction in
aqueous photoresponsive micellar media was not described.
Herein, we report the scope and limitations of this method-
The synthesis of 1 was first described by Shang et al. in
2003,15 but the proposed three-step protocol suffers from a
very poor overall yield of 3%. For the present work, a modified
three-step protocol was followed.16 Azobenzene 3 was
synthesized by oxidative coupling of 4-butylaniline 2 and
phenol via the corresponding diazonium salt. Then, a classical
Williamson etherification of phenol derivative 3 with the
tosylate 4 obtained by selective sulfonatation of the glycol
derivative PEG3 furnished the desired C4-Azo-PEG 1 in 50%
overall yield (Scheme 1).
Received: August 24, 2013
Published: December 2, 2013
© 2013 American Chemical Society
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Scheme 1. Synthetic Pathways to C4-Azo-PEG 1
Figure 2. Overlaid UV spectra (1 scan per 15 s, from 0 to 18 min)
during the isomerization of 1 at 365 nm (500 W lamp). Sample
concentration: 10−4 mol/L.
The surface tension measurements of 1 have been previously
reported, before and after UV irradiation. It has been clearly
demonstrated that 1 forms micelles, and the CMC (critical
micellar concentration) of the trans and the cis forms are 4.1
and 8 μM, respectively.15
The cis/trans equilibrium of 1 was also previously studied
with a 200 W mercury lamp.15 To confirm the ability of the
diazo function to isomerize under UV exposure (Scheme 2), 1
Figure 3. Overlaid UV spectra (1 scan per 15 s, from 0 to 6 min)
during the isomerization of 1 at 254 nm (500 W lamp). Sample
concentration: 10−4 mol/L.
Finally, as already shown for numerous azo derivatives, it must
be pointed out that the cis isomer could not be isolated in pure
form.18
Scheme 2. Isomerization Equilibrium between 1 (trans) and
1 (cis)
Repeating the irradiation of 1 in solution, to switch between
isomers did not reveal any degradation of 1, as the maximum
UV spectrum obtained after each irradiation was consistent to
the previous one (Figure 4).
was analyzed by UV/vis absorption spectroscopy. In our hands,
using a 500 W mercury lamp, irradiation at 365 nm of 1 (trans)
in deionized water at room temperature resulted in a substantial
change in the UV/vis spectrum of 1, due to its switching from
its trans to cis isomers. The absorption band at around 320 nm
was found to decrease gradually with continued irradiation. At
the same time, the bands at around 250 and 420 nm slightly
increase. The absorption bands at 320, 250, and 420 nm are
ascribed to π−π* and n−π* of the trans and the cis forms of the
azo moiety, respectively,17 which is in accordance with the trans
photoisomer 1 (trans) being converted into its cis form. The
maximum isomerization yield was obtained after 14 min of
irradiation at 365 nm (Figure 2).
Figure 4. Reversibility of photoisomerization in 1 solution at 2 × 10−4
mol/L for the trans-to-cis and cis-to-trans processes. The solution was
irradiated alternately with 365 and 254 nm for 14 and 6 min,
respectively. The absorbance at the trans band was recorded after each
illumination.
Results obtained are in accordance with the previously
described ability of 1 to photoisomerize without degradation
regardless of the power of the mercury lamp (500 W vs 200
W), which only allowed decreasing the time necessary to
achieve equilibrium.
To evaluate the potential of the C4-Azo-PEG 1 in micellar
catalysis, the protocol developed in 2005 by Felpin et al. for the
10%Pd/C-mediated allylic substitution in pure water was taken
When irradiated at 254 nm (Figure 3), the cis isomer of 1
returned gradually to its trans form, and the maximum
isomerization yield was obtained after 6 min of irradiation.
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as reference.19 This heterogeneous process uses an inexpensive
and environmentally friendly source of Pd since it is
immobilized on a support and can be easily removed by simple
filtration. Nevertheless, the optimized reaction required a
prolonged heating over 18 h. Also, the authors did not evaluate
the recyclability of the catalytic system. In the present study,
environmental aspects have been respected by minimizing the
reaction time and reusing the catalyst.
Cinnamyl acetate 5 was selected as a model substrate with
the p-toluenesulfinic acid sodium salt (p-TsNa) as nucleophile
(Scheme 3). Catalyst loading and temperature have been
optimized previously (1 mol % of Pd and 70 °C) and will not
be extended upon here.
more efficient with a TOF (turn over frequency) increasing
from 1.33 × 10−3 to 7.96 × 10−3 s−1. A rise in concentration of
the surfactant 1 to 10 CMC was tested. UV analysis of 1 (41
μM, 10 CMC trans) in solution with 10%Pd/C (20 mg)
showed a residual concentration of free C4-Azo-PEG 1 in
solution down to 18.8 μM, largely above the cis form CMC.
Using the concentration of surfactant 1 (41 μM), the Tsuji−
Trost model reaction permitted furnishing the sulfone 6 in 58%
yield after 3 h. To conclude, it seemed that the concentration of
free C4-Azo-PEG 1 should be between CMC trans and CMC
cis. Because of the surfactant adsorption capability of the
charcoal supporting palladium, the amount of surfactant 1 in
the catalyzed Tsuji−Trost reaction has to reach 3 CMC of the
trans form (12.3 μM).
To test the efficiency of C4-Azo-PEG 1, three commercially
available surfactants: the anionic surfactant SDS (sodium
dodecyl sulfate), the cationic surfactant CTAB (cetyl
trimethylammonium bromide), and the nonionic PEG-based
surfactant Tween 20 (Figure 6) were evaluated for a
comparative study in the optimized conditions (pTsNa (2
equiv), 10%Pd/C (1 mol %), PPh3 (4 mol %), surfactant (3
CMC), 70 °C, 3 h).
Scheme 3. Tsuji−Trost Coupling Model Reaction in Water
Without any surfactant, a total conversion was observed after
18 h and the desired sulfone 6 was isolated in 86% yield. As the
concept of this work is based on the capability of the surfactant
to photo-organize and disorganize when submitted to
irradiation, the concentration of 1 needs to be comprised
between the CMC of the trans form (4.1 μM) and the CMC of
the cis form (8 μM). In this regard, the first trial was conducted
with 6 μM of 1, but at this concentration, no enhancement of
the reaction was observed. One potent explanation was the
charcoal capacity in adsorbing 1, leading to a decrease of free
C4-Azo-PEG 1 in water. Indeed, UV analysis experiment
showed that 1 (CMC trans < 6 μM < CMC cis) in water in the
presence of 20 mg of 10%Pd/C (consistent with the tested
Tsuji−Trost experiment) conducted to a concentration of free
C4-Azo-PEG 1 of 0.4 μM, 10 times lower than the CMC of the
trans form (heating this solution did not allow the desorption of
the surfactant). To determine the concentration of free C4-
Azo-PEG 1 comprised between CMC trans and CMC cis, a UV
analysis experiment was performed. A concentration of 1 (12.3
μM, 3 CMC trans) in the presence of 20 mg of 10% Pd/C in
water showed the decrease of 1 in solution down to 5.4 μM,
between the trans form and the cis form CMCs (heating this
solution desorbed the surfactant to 6.9 μM, still below the cis
form CMC). Application of the Tsuji−Trost model reaction
using 1 (12.3 μM) afforded the target compound 6 in 83% yield
after 3 h when 18 h was necessary in the absence of surfactant
(Figure 5). Our catalytic system in such conditions was 6 times
Figure 6. Structure of commercially available surfactants.
When the anionic surfactant SDS was employed, only 26%
yield of 6 was isolated (Table 1, entry 2), which was
significantly less than the 42% yield obtained in the absence
of surfactant (Table 1, entry 1).
This inhibiting effect can be interpreted by electrostatic
repulsions between the surfactant and the anionic nucleophile
p-TsNa at the micelle−water interface.14 The use of cationic
and nonionic surfactants avoided this problem as it can be seen
by comparing results for CTAB, Tween 20, and C4-Azo-PEG 1
Table 1. Surfactant Activities in the First Run under
Conventional Heating
b
entry
surfactant
none
yield of 6 (%)
1
2
3
4
5
6
42
26
80
71
83
96
SDS
CTAB
Tween 20
C4-Azo-PEG
C4-Azo-PEG
a
a
b
Irradiation at 365 nm during 30 min just before extraction. 5 (1
equiv), p-TsNa (2 equiv), 10%Pd/C (1 mol %), PPh3 (4 mol %),
Figure 5. Evolution of yields of reaction versus time.
surfactant (3 CMC), 70 °C, 3 h.
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Figure 7. Comparison of recycling abilities under conventional heating.
(80, 71, and 83% yields, respectively). The good result obtained
with CTAB was not surprising since it has been previously
reported that the CTAB adsorption on the catalyst surface can
enhance the reactivity.20 For all experiments, samples were
submitted to the same direct ethyl acetate extraction except for
entry 6. It is noteworthy that irradiation coupled with extraction
increased the yield to 96% yield (Table 1, entry 6). This
difference in yield (13%) could be directly correlated to the
photochromic properties of 1. The photoirradiation directly
acts on the surfactant to enable a better extraction of 6 from the
media, due to an efficient breakdown of the emulsion, visually
seen experimentally (Table 1, entries 5 and 6).
cross-coupling micellar catalysis, such focus on Suzuki or
Sonogashira couplings.25 As in thermal activation, different
reaction times were tested to develop optimized conditions
under microwave irradiation. To have a good energy saving, we
decided to run the experiment no longer than 30 min.
As described in Figure 8, the best compromise between
efficiency and energy saving was to react for 15 min at 70 °C.
To explore further the scope of C4-Azo-PEG 1 and to
develop an efficient green system, recycling experiments were
performed for the reaction using 10%Pd/C (1 mol %) and the
surfactants at 3 CMC concentration (Figure 7).
After completing each cycle, organic products were extracted
three times with ethyl acetate, and cinnamyl acetate 5 (1 equiv),
p-TsNa (1 equiv), and triphenyl phosphine (4 mol %) were
added again to the aqueous phase. The irradiation effect was
also evaluated when the reaction was conducted with C4-Azo-
PEG 1 (30 min at 365 nm just before extraction). As expected,
the 10%Pd/C-SDS system was not recyclable. Even if SDS is
known to be a Pd stabilizer,21 electrostatic repulsions with the
anionic nucleophile are predominant and no conversion was
observed for the second run. Only two runs with moderate
yields (71% and 67% yield, respectively) could be performed
with Tween 20 before a dramatic decrease. After five runs were
performed with CTAB, a slow decrease at each run was
observed until 0% yield was obtained after the fifth run. When
the direct extraction treatment was applied, using C4-Azo-PEG
1, four cycles were achievable in good yields of, respectively, 83,
99, 92, and 72%, after which no further catalytic effect was
observed. However, when we pretreated for 30 min with 365
nm irradiation, an increase of yield was observed for each cycle
and the catalytic system could be reused for four consecutive
runs without any loss of activity. From these results, it should
be highlighted that the use of the photochromic C4-Azo-PEG
surfactant 1 enhanced the reactivity and recyclability of the
catalytic system.
Figure 8. Evolution of yield vs time of reaction under microwave
irradiation.
It was noted that increasing the time to 30 min allowed only
a modest 5% yield gain. Table 2 shows the results obtained
Table 2. Surfactant Activities and Recycling Abilities under
Microwave Irradiation
b
yield of 6 (%)
entry
surfactant
none
run 1 run 2 run 3 run 4 run 5 run 6
1
2
3
4
5
6
20
26
73
80
64
65
22
0
16
0
SDS
Tween 20
CTAB
0
100
97
94
26
28
26
0
0
C4-Azo-PEG
C4-Azo-PEG
a
24
12
0
a
b
Irradiation at 365 nm during 30 min just before extraction. 5 (1
equiv), p-TsNa (2 equiv), 10%Pd/C (1 mol %), PPh3 (4 mol %),
surfactant (3 CMC), 70 °C, 3 h.
With its high dielectric constant, water is potentially a very
useful solvent for microwave-mediated synthesis.22 Indeed,
microwave heating has been widely recognized as an efficient
tool, and its benefits have been well-documented.23 Since many
reactions are known to result in higher yield and/or shorter
reaction times, this alternative technology was developed in our
group for Suzuki−Miyaura cross-coupling of various uridines in
pure water.24 Nevertheless, to the best of our knowledge, there
are only a few reports on using microwave heating coupled with
under the following conditions: p-TsNa (2 equiv), 10%Pd/C (1
mol %), PPh3 (4 mol %), surfactant (3 CMC), 70 °C,
microwave irradiation, 15 min. As in conventional heating,
particular attention was paid to the recycling ability of the
system and the role of the photochromic surfactant 1. In the
first instance, we observed that the first run under these
conditions gave comparable results between thermal heating
and microwave activation for all commercially available
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surfactants (Figure 7; Table 2, entries 2−4). When no
surfactant was used, the media was recyclable twice with low
yield (Table 2, entry 1).
Under our optimized method using C4-Azo-PEG 1 in
thermal activation, all desired compounds were obtained in
moderate to excellent yields (36−97%). Linear cinnamyl
acetate 5 having an E configuration reacted smoothly with p-
toluenesulfinic acid sodium salt to give the desired sulfone 6 in
96% yield, without any loss of configuration (Table 3, entry 1).
Starting from acetate 5 with morpholine and dibenzylamine as
N-nucleophiles led to the target compounds 11 and 14 in good
yields (75% and 62%, respectively) (Table 3, entries 4 and 7).
Under these conditions, with no additional base in the reaction
medium, no side reaction of saponification was observed. When
C-nucleophiles are tested, a base is necessary in the reaction
medium but led to some competitive saponification of the
starting acetate 5 (10−15% of cinnamyl alcohol isolated). In
these conditions, lower yields can be achieved. However, dimer
17 was obtained with 2,4-pentanedione in a good yield of 80%
(Table 3, entry 10).The use of a hardier O-nucleophile, phenol,
surprisingly led to the target compound 18 in excellent yield
(97%, Table 3, entry 11). The much hindered allylic acetate 7
was found to be a good substrate under the optimized
conditions. As such, compounds 9, 12, and 15 were obtained in
good to excellent yields (Table 3, entries 2, 5, and 8). Despite
its high steric hindrance, compound 15 was obtained in 77%
yield. Finally, the branched allylic acetate 8, as expected, was
found to be less reactive, and the sulfone 10 was obtained in
52% yield. Morpholine as N-nucleophile was found to react
better with the acetate 8, leading to the desired compound 13
in 60% yield. The much more hindered, dibenzylamine, gave
compound 16 but in a modest 36% yield. In this case, the
unreacted acetate 8 was recovered without modification. An
important point that deserves comment is the regioselectivity of
the reaction. Similar to most homogeneous Pd-catalyzed
reactions, only substitution at the least hindered allylic position
is observed. In this respect, this reaction applied to allylic
acetates showed a good range of compatibility with various
nitrogen or sulfur nucleophiles.
Therefore, we can assume that the palladium source kept its
activity to the same extent as with microwave irradiation. SDS is
the less active surfactant under these conditions (Table 2, entry
2) and is not recyclable. More surprisingly, Tween 20, which
was recyclable in conventional heating, performed a good first
run (73% yield) before showing a dramatic loss of activity
(Table 2, entry 3). These last commercially available surfactants
SDS and Tween 20 seemed to lead to a marked deactivation of
palladium in only one run. CTAB, as in conventional heating
(Figure 7), is a serious concurrent to C4-Azo-PEG 1 in terms of
activity and recyclability. The two surfactants CTAB and C4-
Azo-PEG 1 indicated a useful potential (Table 2, entries 4 and
5). The second run was quantitative, but yields dramatically
decreased for the third run. Their behavior was the same when
no irradiation step of the C4-Azo-PEG 1 was included in the
sample treatment (Table 2, entry 5). C4-Azo-PEG 1, as in
conventional heating, proved to be the most interesting
surfactant tested, when submitted to the irradiation−extraction
treatment (i.e., irradiation at 365 nm for 30 min just before
extraction) (Table 2, entry 6).
According to the results presented herein, the increase of the
catalytic activity observed when the reaction medium is
subjected to microwave irradiation (i.e., 15 min vs 3 h under
conventional heating) is due presumably to electric discharge or
hot spots created within the heterogeneous catalyst. This
phenomenon has been previously observed and studied in C−
C and P−C couplings.26 In both conditions, recycling of the
10%Pd/C-C4-Azo-PEG 1 system was conducted (Figure 9).
CONCLUSION
■
In accordance with the objective of green chemistry, the Tsuji−
Trost reaction in aqueous photoresponsive micellar media
proved to be efficient under conventional heating and
microwave irradiation. As C4-Azo-PEG 1 can organize and
disorganize in aqueous solution under UV irradiation, it allows
a better extraction of the products formed due to its
photochromism property and an enhancement of reactivity
and recyclability of the catalytic system. For this study,
conventional heating seemed to be more favorable than
microwave irradiation. This attractive technique allowed a
decrease in reaction time and a savings in energy, but the
downside was a faster deactivation of catalyst. Our optimized
method under conventional heating was extended to much
hindered and branched allylic acetates, and the system showed
a good range of compatibility with various nucleophiles. As
photochromic surfactants based on azobenzene moieties and, in
particular, C4-Azo-PEG 1 are really interesting and versatile
compounds, their potential in catalysis should be more
extensively explored.
Figure 9. Comparison of recycling abilities between conventional
heating and microwave irradiation in the presence of C4-Azo-PEG 1
after irradiation at 365 nm during 30 min just before extraction.
The first and the second cycles gave similar results.
Nevertheless, the activity of the catalyst decreased drastically
during the third cycle for the microwave heated system. This
tendency was confirmed during the fourth run. In these
conditions, the metal suffered the fastest deactivation under
microwave irradiation than conventional heating. The decrease
in catalytic activity could result from the aggregation of
palladium nanoparticles or blockage of the active sites.21 One
potent explanation was that microwave heating creates small
and locally superheated, highly active sites, leading to an
acceleration of the deactivation when the temperature
increased.27
EXPERIMENTAL SECTION
■
Materials. All commercially available products and solvents were
used without further purification. Reactions were monitored by TLC
(Kieselgel 60F254 aluminum sheet) with detection by UV light or
potassium permanganate acidic solution. Column chromatography was
To explore further the scope of this new process, the reaction
of three different allylic acetates 5, 7, and 8 with some different
nucleophiles was examined (Table 3).
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Table 3. Scope of the Tsuji−Trost Reaction
performed on silica gel 40−60 μm. Flash column chromatography was
performed on an automatic apparatus, using silica gel cartridges. UV
analyses were performed on a UV/vis spectrophotometer coupled with
an optic fiber. A 500 W mercuric lamp was used for the irradiation of
bath. The crude solution was added dropwise to a solution of phenol
(20.7 g, 0.22 mol) in soda (100 mL, 6 M). Finally, the solution was
quenched with HCl. The product 3 was obtained after filtration and
recrystallization from pentane as a red solid (40.1 g, 79%). Analyses
are consistent with the literature.15
1
the C4-Azo-PEG solutions. H and 13C NMR spectra were recorded
1
on a 400 MHz/54 mm ultralong hold. Chemical shifts (δ) are quoted
in parts per million (ppm) and are referenced to TMS as an internal
standard. Coupling constants (J) are quoted in hertz. Microwave
experiments were conducted in a commercial microwave reactor
especially designed for synthetic chemistry. Monowave300 (Anton
Paar, Austria) is a monomode cavity with a microwave power delivery
system ranging from 0 to 850 W. The temperatures of the reactions
were monitored via a contactless infrared pyrometer, which was
calibrated in control experiments with a fiber-optic contact
thermometer. Sealed vessels and a magnetic stir bar inside the vessel
were used. Temperature and power profiles were monitored in both
cases through the software provided by the manufacturer.
mp = 80 °C. H NMR (400 MHz, CDCl3): δ 7.85 (d, J = 8.8 Hz,
2H), 7.79 (d, J = 8.3 Hz, 2H), 7.30 (d, J = 8.3 Hz, 2H), 6.92 (d, J = 8.8
Hz, 2H), 2.68 (t, J = 7.7 Hz, 2H), 1.75 (bs, 1H), 1.64 (quin, J = 7.6
Hz, 2H), 1.37 (sex, J = 7.5 Hz, 2H), 0.94 (t, J = 7.3 Hz, 3H). 13C NMR
(100 MHz, CDCl3): δ 158.0, 150.8, 147.1, 145.9, 129.0 (2×), 124.7
(2×), 122.5 (2×), 115.7 (2×), 35.5, 33.4, 22.3, 13.9.
Triethyleneglycol Monotosylate (4). To a solution of triethylene
glycol PEG3 (11 g, 73.3 mmol), triethylamine (2.6 mL, 19.1 mmol),
and DMAP (45 mg, 0.37 mmol) in 95 mL of DCM was added tosyl
chloride (3.5 g, 18.1 mmol) at 5 °C, and the mixture was stirred for 4
h. The resulting mixture was washed with 1 N HCL, H2O, and brine.
The organic layer was dried over MgSO4 and concentrated under
vacuum. The residue was purified by silica gel chromatography
(EtOAc/cyclohexane 7:3) to obtain the title compound 4 as yellow oil
(4.2 g, 75%).28
Synthesis of C4-Azo-PEG 1. 4-Butyl-4′-hydroxyazobenzene (3).
To a solution of 4-butylaniline (2) (30 g, 0.20 mol) in 37% HCl (50
mL) and water (25 mL) was added NaNO2 (16.6 g, 0.24 mol) in water
(25 mL) dropwise in 30 min. The reaction was conducted in an ice
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1H NMR (400 MHz, CDCl3): δ 7.80 (d, J = 8.2 Hz, 2H), 7.35 (d, J
= 8.0 Hz, 2H), 4.16 (t, J = 4.7 Hz, 2H), 3.70 (q, J = 4.7 Hz, 4H), 3.61
(s, 4H), 3.57 (t, J = 4.5 Hz, 2H), 2.45 (s, 3H), 2.32 (s, 1H). 13C NMR
(100 MHz, CDCl3): δ 144.8, 132.8, 129.7 (2×), 127.9 (2×), 72.4,
70.7, 70.2, 69.1, 68.6, 61.6, 21.6.
136.8, 133.3, 128.5, 127.5 (2×), 126.3, 126.1 (2×), 67.0 (2×), 61.4,
53.6 (2×).
4-(1,3-Diphenylallyl)morpholine (12).28 Flash chromatography
(0% EtOAc−cyclohexane to 50% EtOAc−cyclohexane) gave the
desired product 12 as a colorless solid (502 mg, 90%). Analyses are
consistent with the literature.
Triethylene Glycol Mono(4-butylazobenzene) Ether (C4-Azo-PEG
1). In a round-bottom flask under N2, triethyleneglycol monotosylate
(4) (4.4 g, 14.5 mmol), K2CO3 (9.9 g, 72.3 mmol), and LiCl (20 mg, 3
mol %) were dissolved in MeCN (150 mL). A solution of 4-butyl-4′-
hydroxyazobenzene (3) (3.9 g, 15.43 mmol) in MeCN (50 mL) was
added dropwise. The mixture was refluxed under N2 for 18 h. The
solvent was then evaporated under vacuum. The residue was dissolved
in DCM and then washed with brine (3 × 100 mL). The organic layer
was dried over MgSO4 and concentrated under vacuum. The product
1 was purified by silica gel chromatography (EtOAC/cyclohexane 7:3)
to obtain the desired compound as a yellow solid after recrystallization
from pentane (2.6 g, 85%). Analyses are consistent with the
literature.15
mp = 65 °C. 1H NMR (400 MHz, CDCl3): δ 7.21−7.44 (m, 10H),
6.60 (d, J = 15.8 Hz, 1H), 6.32 (dd, J=16,0, J=8,8 Hz, 1H), 3,80 (d, J =
8,8 Hz, 1H), 3.74 (t, J = 4,8 Hz, 4H), 2,56 (m, 2H), 2.42 (m, 2H). 13
C
NMR (100 MHz, CDCl3): δ 168.4, 167.8, 140.3, 137.0 (2×), 132.0
(2×), 129.3 (2×), 128.9, 128.7, 128.0 (2×), 127.8, 127.3 (2×), 67.2,
61.4 (2×).
4-(Cyclohex-2-enyl)morpholine (13).29 Flash chromatography (0%
EtOAc−cyclohexane to 100% EtOAc−cyclohexane) gave the desired
product 13 as a colorless oil (200 mg, 60%). Analyses are consistent
with the literature.
1H NMR (400 MHz, CDCl3): δ 5.89 (d, J = 10.4 Hz, 1H), 5.60 (d, J
= 10.4 Hz, 1H), 3.66−3.69 (m, 4H), 3.11−3.12 (m, 1H), 2.50−2.52
(m, 4H), 1.94−1.95 (m, 2H), 1.76−1.78 (m, 2H), 1.50−1.53 (m, 2H).
13C NMR (100 MHz, CDCl3): δ 130.4 (2×), 128.9 (2×), 67.6, 60.4,
49.3, 25.3, 23.1, 21.5.
1
mp = 60 °C. H NMR (400 MHz, CDCl3): δ 7.91 (d, J = 8.8 Hz,
2H), 7.82 (d, J = 8.2 Hz, 2H), 7.31 (d, J = 8.2 Hz, 2H), 7.04 (d, J = 8.8
Hz, 2H), 4.24 (t, J = 4.6 Hz, 2H), 3.92 (t, J = 4.6 Hz, 2H), 3.72−3.78
(m, 6H), 3.65 (t, J = 4.4 Hz, 2H), 2.70 (t, J = 7.7 Hz, 2H), 2.34 (s,
1H), 1.66 (quin, J = 7.6 Hz, 2H), 1.39 (sex, J = 7.4 Hz, 2H), 0.96 (t, J
= 7.3 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 160.9, 150.9, 147.2,
145.8, 129.0 (2×), 124.5 (2×), 122.5 (2×), 114.7 (2×), 72.4, 70.8,
70.3, 69.6, 67.6, 61.7, 35.5, 33.4, 22.3, 13.9.
N,N-Dibenzyl-3-phenylprop-2-enamine (14).30 Flash chromatog-
raphy (0% EtOAc−cyclohexane to 50% EtOAc−cyclohexane) gave the
desired product 14 as a yellowish oil (388 mg, 62%). Analyses are
consistent with the literature.
1H NMR (400 MHz, CDCl3): δ 7.18−7.26 (m, 15H), 6.52 (d, J =
15.9 Hz, 1H), 6.28 (dt, J = 6.6, 13.4 Hz, 1H), 3.61 (s, 4H), 3.20 (d, J =
6.2 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 139.6 (2×), 137.2,
132.4, 128.8, 128.5 (4×), 128.2 (2×), 127.7 (4×), 127.3, 126.8 (2×),
126.2 (2×), 57.9 (2×), 55.7.
General Procedure for the Tsuji−Trost Reaction. A 30 mL
MW vessel was charged with 10%Pd/C (20 mg, 1 mol %), PPh3 (20
mg, 4 mol %), the desired allylic acetate (2 mmol), and nucleophile (4
mmol). When necessary, potassium carbonate (4 mmol) was added in
the medium. The solution of the surfactant in water (10 mL) was then
added. The mixture was heated at 70 °C for 3 h (conventional
heating) or 15 min (MW irradiation. The final product was extracted
with EtOAc (3 × 5 mL) before purification. When necessary, the
extraction can be prefaced by a 30 min irradiation under a 365 nm
lamp. For recycling tests, only allylic acetate (2 mmol), PPh3 (4 mol
%), and nucleophile (2 mmol) were introduced.
Dibenzyl-(1,3-diphenylallyl)amine (15).31 Flash chromatography
(0% EtOAc−cyclohexane to 100% EtOAc−cyclohexane) gave the
desired product 15 as a white solid (600 mg, 77%). Analyses are
consistent with the literature.
1
mp = 112 °C. H NMR (400 MHz, CDCl3): δ 7.12−7.48 (m,
trans-Cinnamyl-p-tolyl Sulfone (6).19 Flash chromatography (0%
EtOAc−cyclohexane to 50% EtOAc−cyclohexane) gave the desired
product 6 as a white powder (522 mg, 96%).
20H), 6.44 (m, 2H), 4.36 (d, J = 6.9 Hz, 1H), 3.65 (d, J = 13.8 Hz,
2H), 3.52 (d, J = 13.8 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 54.0
(2×), 65.1, 126.5 (2×), 126.8 (2×), 127.1, 127.6, 127.7, 128.2 (2×),
128.3 (2×), 128.4 (4×), 126.6 (2×), 126.7 (4×), 134.1, 137.0, 140.0
(2×), 141.9.
mp = 120 °C. 1H NMR (400 MHz, CDCl3): δ 7.69 (d, J = 8.3 Hz,
2H), 7.20−7.27 (m, 7H), 6.32 (d, J = 15.5 Hz, 1H), 6.04 (quin, J = 7.5
Hz, 1H), 3.86 (dd, J = 0.8, 7.5, 2H), 2.37 (s, 3H). 13C NMR (100
MHz, CDCl3): δ 144.7, 138.9, 135.8, 135.5, 129.6 (2×), 128.6 (2×),
128.5 (2×), 128.4, 126.5 (2×), 115.3, 60.5, 21.5.
N,N-Dibenzylcyclohex-2-enamine (16).19 Flash chromatography
(0% EtOAc−cyclohexane to 100% EtOAc−cyclohexane) gave the
desired product 16 as a colorless oil (199 mg, 36%). Analyses are
consistent with the literature.
1,3-Diphenyl-2-propenyl-p-tolyl Sulfone (9).19 Flash chromatog-
raphy (0% EtOAc−cyclohexane to 100% EtOAc−cyclohexane) gave
the desired product 9 as a colorless solid (362 mg, 52%). Analyses are
consistent with the literature.
1H NMR (400 MHz, CDCl3): δ 7.13−7.33 (m, 10H), 5.65−5.76
(m, 2H), 3.68 (d, J = 14.1 Hz, 2H), 3.46 (d, J = 14.1 Hz, 2H), 3.45 (m,
1H), 1.80−1,92 (m, 3H), 1.72 (m, 1H), 1.53 (m, 2H). 13C NMR (100
MHz, CDCl3): δ 141.1 (2×), 131.0, 130.2 (4×), 128.6 (4×), 128.3
(2×), 126.8, 54.7 (2×), 54.0, 25.5 (2×), 22.0.
mp = 158−159 °C. 1H NMR (400 MHz, CDCl3): δ 7.53 (d, J = 8.4
Hz, 2H), 7.29−7.36 (m, 10H), 7,20 (d, J = 8.0 Hz, 2H), 6.55−6.58
(m, 2H), 4.81 (d, J = 7.6 Hz, 1H), 2.40 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 144.5, 137.9, 135.9, 134.4, 132.5 (2×), 129.7 (2×), 129.3
(5×), 128.8, 128.6 (2×), 128.4 (2×), 126.7, 120.2, 75.3, 21.6.
Cyclohex-2-enyl-p-tolyl Sulfone (10).19 Flash chromatography (0%
EtOAc−cyclohexane to 100% EtOAc−cyclohexane) gave the desired
product 10 as a colorless oil (245 mg, 52%). Analyses are consistent
with the literature.
3,3-Dicinnamylpentane-2,4-dione (17).32 Flash chromatography
(0% EtOAc−cyclohexane to 100% EtOAc−cyclohexane) gave the
desired product 17 as colorless crystals (265 mg, 80%). Analyses are
consistent with the literature.
1
mp = 60−61 °C. H NMR (400 MHz, CDCl3): 7.15−7.23 (m,
10H), 6.40 (d, J = 16.0 Hz, 2H), 5.86 (m, 2H), 2.78 (dd, J = 7.6 Hz, J
= 1.2 Hz, 2H), 2.10 (s, 6H). 13C NMR (100 MHz, CDCl3): δ 205.8
(2×), 136.8 (2×), 134.3 (2×), 128.6 (4×), 127.6 (2×), 126.2 (4×),
123.3 (2×), 70.8, 34.6 (2×), 27.4 (2×).
1H NMR (400 MHz, CDCl3): δ 7.74 (d, J = 8.3 Hz, 1H), 7.33 (d, J
= 7.9 Hz, 1H), 6.02−6.09 (m, 1H), 5.73−5.78 (m, 1H), 3.69−3.72 (m,
1H), 2.44 (s, 3H), 1.80−1.85 (m, 5H), 1.46−1.49 (m, 1H). 13C NMR
(100 MHz, CDCl3): δ 144.5, 135.1, 134.4 (2×), 129.6 (2×), 129.1
(2×), 61.8, 24.3, 22.7, 21.6, 19.5.
Cinnamylphenylether (18).33 Flash chromatography (0% EtOAc−
cyclohexane to 100% EtOAc−cyclohexane) gave the desired product
18 as a white powder (408 mg, 97%). Analyses are consistent with the
literature.
4-Cinnamylmorpholine (11).19 Flash chromatography (0%
EtOAc−cyclohexane to 100% EtOAc−cyclohexane) gave the desired
product 11 as a colorless oil (304 mg, 75%). Analyses are consistent
with the literature.
mp = 64−65 °C. 1H NMR (400 MHz, CDCl3): 7.14−7.33 (m, 7H),
6.86−6.90 (m, 3H), 6.64 (d, J = 15.8 Hz, 1H), 6;33 (m, 1H), 4.61 (dd,
J = 5.6 Hz, J = 1.5 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 158.7,
136.5, 133.0, 129.5 (2×), 128.6 (2×), 127.9, 126.6 (2×), 124.6, 120.9,
114.8 (2×), 68.6.
1H NMR (400 MHz, CDCl3): δ 7.20−7.38 (m, 5H), 6.52 (d, J =
16,0 Hz, 1H), 6.25 (dt, J = 6.8, 13.6 Hz, 1H), 3.73 (t, J = 4.4 Hz, 4H),
3.14 (d, J = 6,8, 2H), 2,50 (m, 4H). 13C NMR (100 MHz, CDCl3): δ
499
dx.doi.org/10.1021/jo401737t | J. Org. Chem. 2014, 79, 493−500

The Journal of Organic Chemistry
Article
Bourdauducq, P.; Couturier, J. L.; Kervennal, J.; Mortreux, A. Appl.
Catal., A 1995, 131, 167.
(15) Shang, T.; Smith, K. A.; Hatton, T. A. Langmuir 2003, 19,
ASSOCIATED CONTENT
■
S
* Supporting Information
1H experiments spectra are provided. This material is available
free of charge via the Internet at http://pubs.acs.org.
10764.
(16) Nalluri, S. K. M.; Voskuhl, J.; Bultema, J. B.; Boekema, E. J.;
Ravoo, B. J. Angew. Chem., Int. Ed. 2011, 50, 9747.
(17) Hamon, F.; Djedaini-Pilard, F.; Barbot, F.; Len, C. Tetrahedron
2009, 65, 10105.
AUTHOR INFORMATION
Corresponding Author
*E-mail: christophe.len@utc.fr. Fax: (+33)(0)3 44 97 15 91.
Notes
■
(18) Basheer, M. C.; Oka, Y.; Mathews, M.; Tamaoki, N. Chem.
Eur. J. 2010, 16, 3489.
(19) Felpin, F.-X.; Landais, Y. J. Org. Chem. 2005, 70, 6441.
(20) (a) Shinde, M. M.; Bhagwat, S. S. Colloids Surf., A 2011, 380,
201. (b) Arcadi, A.; Cerichelli, G.; Chiarini, M.; Correa, M.; Zorzan, D.
Eur. J. Org. Chem. 2003, 20, 4080.
(21) Saha, D.; Dey, R.; Ranu, B. C. Eur. J. Org. Chem. 2010, 31, 6067.
(22) Alonso, F.; Beletskaya, I. P.; Yus, M. Tetrahedron 2008, 64,
3047.
(23) For a recent book chapter, see: Fihri, A.; Len, C. Microwave-
assisted Coupling Reactions in Aqueous. In Aqueous Microwave Assisted
Chemistry; Polshettiwar, V., Varma, R. S., Eds.; Royal Society of
Chemistry: Cambridge, U.K., 2010; Chapter 3, p 55.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The Reg
́
ion Picardie is gratefully acknowledged for its financial
ieure de Chimie
ale) for her research fellowship. We are also
support. F.M. thanks ESCOM (Ecole Super
Organique et Miner
grateful to some fourth year students for their implication
during preliminary works on catalysis.
́
́
(24) Gallagher-Duval, S.; Herve,
New J. Chem. 2013, 37, 1989.
́
G.; Sartori, G.; Enderlin, G.; Len, C.
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