Solvent-free chelation-assisted hydroacylation of olefin by rhodium(I) catalyst under microwave irradiation

Article abstract of DOI:10.1039/b200442a

A solvent-free protocol for the rhodium(I)-catalyzed intermolecular hydroacylation was achieved under microwave irradiation to furnish various ketones in high yields. The reactivity was improved by the addition of aniline as well as 2-amino-3-picoline and benzoic acid to induce a transimination, which facilitates the formation of intermediate aldimine. A comparison of the reactivity between the reaction performed under the conventional heating mode and the microwave irradiation using monomode reactor revealed an important specific microwave effect during the chelation-assisted hydroacylation. It is supposed that the observed specific microwave effect mainly originates from the formation of aldimine by condensation of aldehyde and amine, which leads to a development of charges in the transition state. This result confirms that the rate-determining step of the reaction is the initial condensation step rather than the subsequent hydroiminoacylation step.

Full text of DOI:10.1039/b200442a

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Solvent-free chelation-assisted hydroacylation of olefin by
rhodium(I) catalyst under microwave irradiation
André Loupy,*a Saber Chatti,a Sarah Delamare,a Dae-Yon Lee,b Jong-Hwa Chungb and
Chul-Ho Jun*b
1
a Laboratoire des Réactions Sélectives sur Supports, ICMO, CNRS UMR 8615, Bâtiment 410,
Université Paris-Sud, 91405 Orsay Cedex, France. E-mail: aloupy@icmo.u-psud.fr;
Fax: 33 1 69 15 46 79; Tel: 33 1 69 15 7650
b Department of Chemistry, Yonsei University, Seoul, 120-749, South Korea.
E-mail: junch@yonsei.ac.kr; Fax: 82 2 364 7050; Tel: 82 2 2123 2644
Received (in Cambridge, UK) 14th January 2002, Accepted 11th April 2002
First published as an Advance Article on the web 25th April 2002
A solvent-free protocol for the rhodium()-catalyzed intermolecular hydroacylation was achieved under microwave
irradiation to furnish various ketones in high yields. The reactivity was improved by the addition of aniline as well
as 2-amino-3-picoline and benzoic acid to induce a transimination, which facilitates the formation of intermediate
aldimine. A comparison of the reactivity between the reaction performed under the conventional heating mode
and the microwave irradiation using monomode reactor revealed an important specific microwave effect during the
chelation-assisted hydroacylation. It is supposed that the observed specific microwave effect mainly originates from
the formation of aldimine by condensation of aldehyde and amine, which leads to a development of charges in the
transition state. This result confirms that the rate-determining step of the reaction is the initial condensation step
rather than the subsequent hydroiminoacylation step.
chelation-assisted hydroacylation using a catalyst system of
Introduction
Rh() complex and 2-amino-3-picoline† demonstrating its
potential utility as a versatile protocol for the synthesis of
ketones.13 We were consequently encouraged to apply solvent-
free microwave-assisted procedure to this reaction for the sake
of enhanced reactivity, and hopefully for achieving green chem-
istry. Herein we wish to report a microwave-assisted inter-
molecular hydroacylation of olefin catalyzed by Rh() complex.
A study on the effect of microwave activation was also
undertaken.15
For the purpose of modernizing and improving classical syn-
thetic procedures to be more economical, clean, safe and easy-
to-perform, solvent-free organic synthesis is of great interest as
one of the major tools for green chemistry.1 The main interest
lies in the fact that: a) it avoids the use of solvents which are
very often toxic, expensive, and problematic to use and to
remove, b) it allows operation at higher temperatures as there is
no limitation of the boiling points of solvents, c) it enhances the
reactivity by increasing the concentration.
Solvent-free methods have been shown to be very efficient
and advantageously coupled with microwave (MW) activation,2
and many organic reactions have been carried out using
“microwave-induced organic reaction enhancement” (MORE)
technique delivering high yields in a short reaction time com-
pared with the conventional heating mode performed in pre-
heated thermostat oil bath.3 Such an enhanced reactivity is
supposed to arise mainly from rapid and homogeneous heating
of the bulk reaction mixture by microwave irradiation. On the
other hand, there are many examples implying that the inter-
vention of a specific microwave effect, i.e. not purely thermal
effects, also plays an important role depending on the medium
and the mechanism of the reaction.4
Results and discussion
In our experiment, in the absence of any additional solvent,
benzaldehyde (1a) reacted with dec-1-ene (2a) in the presence of
(PPh3)3RhCl (Wilkinson’s complex, 3), 2-amino-3-picoline (4),
and benzoic acid (5) under microwave irradiation for 30 min to
afford 1-phenylundecan-1-one (6a) in a 83% yield (eqn. 1).
(1)
Undoubtedly, it is quite desirable to develop microwave-
promoted transition metal catalyzed reactions because of the
versatile utilities of transition metals in organic synthesis.
Recently, some valuable transition metal catalyzed reactions
such as transfer hydrogenation,5 phosphonation of aryl
halides,6 allylic alkylation,7 Heck-type reaction,8 Suzuki,9
Stille,9 and Sonogashira couplings10 have been successfully
accomplished using a microwave technique. Even though the
examples are still rare, some cases have been described for MW-
mediated palladium-catalyzed reactions without using any
solvent.11
To certify whether any specific microwave effect exists, a con-
trol experiment was conducted under the same reaction condi-
tions but in the preheated oil bath with comparable profiles of
temperature during the reaction (Fig. 1) to afford 6a in only 50%
yield. This result clarifies that there is a significant specific
microwave effect, which gives rise to enhancement of reactivity,
in addition to thermal effect, under microwave irradiation (see
below).
Intermolecular hydroacylation,12,13 a synthetic method for
ketones directly from aldehydes and olefins catalyzed by transi-
tion metal complexes, is a prominent way to obtain ketones in
the light of atom economy.14 We have recently developed a
† The IUPAC name for picoline is methylpyridine.
DOI: 10.1039/b200442a
1280
J. Chem. Soc., Perkin Trans. 1, 2002, 1280–1285
This journal is © The Royal Society of Chemistry 2002

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Table 1 The chelation-assisted hydroacylation of various olefins (2) with benzaldehyde (1a) under microwave irradiationa
Entry
Olefin (2)
T /ЊC
Time/min
Product (6)
isolated yield (%)b
1
Dec-1-ene (2a)
(2a)
140
140
140
60
100
–
30
30
10
60
60
10
10
10
6a
6a
6b
6c
6c
6c
6d
6e
83 (50)
12
84 (30)
0
31
75
2c
3
Allylbenzene (2b)
Hex-1-ene (2c)
(2c)
4
5
6d
7d
8d
(2c)
3,3-Dimethylbut-1-ene (2d)
Oct-1-ene (2e)
–
–
69
75
a The reactions were conducted at 140 ЊC under the continuous microwave irradiation (see Fig. 1), unless otherwise designated. b Yields in parenthesis
were obtained from the reaction conducted under the same condition, but in preheated oil bath at 140 ЊC. c The reaction was conducted in the absence
of benzoic acid 5. d The reactions were conducted in closed vessels using a domestic microwave oven with 5 mol% of 3.
oven to give good yields of corresponding ketones with 5 mol%
of 3 (entries 6–8).
The mechanism of the reaction is depicted in Scheme 1.
Scheme 1
Fig. 1 Temperature and irradiation power profiles monitored during
the reaction of 1a and 2a under microwave irradiation or conventional
heating at 140 ЊC.
Initially, aldehyde 1a and 2-amino-3-picoline 4 condense to
form intermediate aldimine 7a catalyzed by benzoic acid 5.
Then, 7a and 2a undergo hydroiminoacylation19 under catalyst
3 to give ketimine 8a, which is hydrolyzed by H2O generated
during the condensation to yield ketone 6a as the final product.
It is quite reasonable to assume that the specific microwave
effect might originate from the condensation of 1a and 4, since
it leads to a development of charges in the transition state (9)
inducing thus an important dipole–dipole interaction (Scheme
2).4 In this circumstance, molecules are sensitive to the electric
Various olefins were also examined and the main results are
summarized in Table 1. The reactions were carried out either in
a monomode microwave reactor (entry 1–5) or in a multimode
domestic microwave oven (entry 6–8). A monomode reactor
allows operation to be carried out with a homogeneous electric
field due to focused wave irradiation. An accurate control and
measurement of temperature by IR detection was made with
monitoring at a constant value thanks to emitted microwave
power modulation.2a,16
The important role of carboxylic acid 5 in the reaction13d was
confirmed by the result obtained from the reaction performed
in its absence, which afforded only 12% yield of 6a (entry 2)
instead of 83% in its presence (entry 1). Allylbenzene (2b)
reacted with 1a readily to afford a good yield (84%) of 1,4-
diphenylbutan-1-one (6b) in a short reaction time of 10 min. In
this reaction, a specific microwave effect was observed by com-
parison with the yield (only 30%) obtained from the reaction
performed in the preheated oil bath at 140 ЊC (entry 3). Since it
was impossible to carry out the reaction with hex-1-ene (2c) at
high temperature due to its low boiling point (60–61 ЊC), at
which temperature the reaction did not proceed at all (entry 4),
the reaction was performed at moderate temperature, 100 ЊC,
to afford only a 31% yield of 1-phenylheptan-1-one (6c) in a
long reaction time (1 h, entry 5). We found it beneficial to use
a domestic microwave oven with closed reaction vessels,‡17
although it is not easy to control the temperature and
microwave power.§18 Therefore, the reactions with 2c and other
volatile olefins such as 3,3-dimethylbut-1-ene (2d) and oct-1-ene
(2e) were carried out successfully using domestic microwave
Scheme 2
field, which results in an increased stabilization of the dipolar
transition state compared with its less polar ground state under
microwave irradiation.
To check the possible intervention of specific microwave
effect during hydroiminoacylation of 2a (i.e. the formation of
8a from 7a in Scheme 1), the reaction of 7a and 2a was under-
taken under both the activation modes (eqn. 2, Table 2).
From these results, it is clear that the specific microwave effect
observed during this reaction is highly dependent on the
temperature level as the same effect appeared when the reaction
was performed under reduced temperature and/or reaction
§ Since it is not easy to control the level of power, all the reactions were
performed under this condition without any modification. The irradi-
ation power of domestic microwave oven was determined as approxi-
mately 700 W, the full power the equipment can generate, according to
the known procedure (see ref. 18).
‡ A caution should be addressed since occasional explosions have been
reported when using a domestic oven in sealed vessel (see ref. 17). Of
course, we carried out the reactions on a small scale without any
mishaps.
J. Chem. Soc., Perkin Trans. 1, 2002, 1280–1285
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Table 3 The chelation-assisted hydroacylation of 2a with anisalde-
hyde (1b) under microwave irradiation
Table 2 The hydroiminoacylation of dec-1-ene (2a) with aldimine 7a
under solvent-free conditions (eqn. 2)
Isolated yield
of 6a (%)
b
Entry
T /ЊC
t/min
MWa
∆
1
100
120
140
5
5
10
40
74
85
22
52
79
2
3c
a MW = microwave irradiation. b ∆ = conventional heating. c Identical
results were observed with or without 5.
time.¶ However, it is evident that the overall specific effect
observed during the chelation-assisted hydroacylation (eqn. 1)
derives from the initial condensation step for aldimine forma-
tion, and this is the rate-determining step as there is no specific
microwave effect in the second step within 10 min at 140 ЊC
(Table 2, entry 3) whereas it is very important in the total pro-
cess (30 min at 140 ЊC, Table 1, entry 1). This is also reinforced
by the fact that there is no enhancement of reactivity by the
addition of 5 in the course of hydroiminoacylation.
Entry
Aniline(10)
T /ЊC
t/min
Isolated yield (%)a
1
2
3
4
–
–
–
–
140
160
160
180
160
160
100
30
30
120
30
30
30
47
40
52
37
84
92 (95)
90 (48)
5
100 mol%
100 mol%
100 mol%
(2)
6b
7b
30
a Yields in parenthesis were obtained from the reactions conducted in a
The existence of non-thermal effects in microwave-assisted
chemical reaction still remains controversial.20 It has been sug-
gested that the rate increases in the reactions carried out under
solvent-free conditions could be due to differential heating
(temperature heterogeneity),21 which could be minimized by
using a monomode reactor (field homogeneity) and mechanical
stirring as in the case of the reactions we carried out. Also it has
been shown that reactions under homogeneous conditions22 did
not have as high a rate enhancement as a heterogeneous cata-
lyst, which is probably due to the higher localized temperature
at the active site of the catalyst.
Prompted by these results, other aldehydes were examined
with solvent-free microwave-assisted hydroacylation. Disap-
pointingly, the reaction of anisaldehyde (1b) and 2a furnished
only a low yield of 1-(4-methoxyphenyl)undecan-1-one (6f,
47%) under the same reaction conditions (Table 3, entry 1). A
possible explanation could be the existence of the electron
donating group in the para position that is unfavourable for the
condensation step. The influence of temperature or reaction
time was not so significant (Table 3, entry 2–4).
preheated oil bath at the same temperature. b A 40 mol% of 4 was used.
Hence aniline (10) was added to the catalyst system in order
to induce transimination, and an improved yield of 84% was
obtained (entry 5). Increasing the amount of 4 up to 40 mol%,
improved the yield to 92% (entry 6) and the yield was still high
at lower temperature of 100 ЊC to give 90% after 30 min (entry
7).
When the reaction was carried out at high temperature, 160
ЊC, the yields are very similar regardless of the mode of acti-
vation, microwave irradiation or conventional heating, and gave
yields of 92% and 95% 6f, respectively (entry 6). However, at
100 ЊC, an important specific microwave effect was observed, as
the yield obtained under conventional heating mode was only
48%, by far lower than that under microwave irradiation (90%,
entry 7). The profile of temperatures for both modes of acti-
vation and microwave power is shown in Fig. 2.
The magnitude of specific microwave effects is known to be
highly dependent on temperature. Similar observations have
Already we found that the reactivity in hydroacylation was
dramatically improved using a transimination protocol,23 which
facilitates the formation of intermediate aldimine (e.g. 7a)
through the initial facile formation of 7b, followed by rapid
transimination with 4 to form 7a (Scheme 3).13d,24
Scheme 3
¶ The origin of the specific microwave effect observed in the hydro-
iminoacylation step is not clear, but it is possible that a polar inter-
mediate or transition state might be generated by complexation of
rhodium with nitrogen atoms.
Fig. 2 Temperature and irradiation power profiles monitored during
the reaction of 1b and 2a under microwave irradiation and conventional
heating at 100 ЊC (Table 3, entry 7).
1282
J. Chem. Soc., Perkin Trans. 1, 2002, 1280–1285

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Table 4 The microwave-assisted hydroacylation of olefins (2) with various aldehydes (1) using transimination
Isolated yield (%)
b
Entry
R1 (1)
H (1a)
R2 (2)
MethodaT /ЊC
t/min
Product (6)
MW
∆
1
2
3
4
5
6
7
8
n-C8H17(2a)
A/100
B
A/100
B
B
A/100
B
A/140
A/160
A/120
B
A/160
A/140
A/160
A/140
30
10
60
10
10
10
10
10
60
30
10
60
30
10
60
6a
6a
6c
6c
6d
6f
48
95
74
84
91
90
93
92
12
85
60
83
21
91
86
30
–
14
–
2a
PhCH2(2c)
2c
But (2d)
2a
–
MeO (1b)
Me2N (1c)
48
–
48
–
36
–
57
–
2a
6f
2b
6g
6h
6h
6h
6i
9c
10
11
12
13c
14
15
2a
2a
2a
2b
CF3 (1d)
2a
6j
6j
6k
2a
52
33
2b
a The reaction was carried out either in open vessel using monomode microwave reactor with 10 mol% of 3 (Method A) or in closed vessel using
domestic microwave oven with 5 mol% of 3 (Method B). b The reaction was conducted under same condition (either method A or B), but in
preheated oil bath. c The reaction was carried out in the absence of 10. A 20 mol% of 4 was used.
been made in some studies where specific microwave effects
appeared at relatively low temperatures (here 100 ЊC) whereas
they are masked at higher temperatures where yields of con-
ventionally heated reactions are also elevated.25
Other aldehydes were applied to the microwave-assisted
hydroacylation using the transimination technique and the
results are summarized in Table 4.
The rate enhancements in the reactions shown in Table 4
(entry 3, 6, 8, 10, 12, 14, and 15) suggest the participation of
an effect other than the thermal microwave effect. Considering
the mechanism of the reaction (Scheme 3), the specific micro-
wave effect might derive from the condensation step of alde-
hydes and aniline 10, which develops a dipolar transition state
11.
As for 1a, the involvement of transimination permitted
enhanced reactivity to give corresponding ketones in good
yields (85–95%) under short reaction times (entries 1–5). It is
noteworthy that 2c also gave a fairly good yield (74%) of 6c in
the presence of 10 (entry 3) compared with in its absence (Table
1, entry 5, 31%), even though it was carried out in the open
vessel instead of the closed vessel. Aldehydes bearing either
electron donating groups or electron withdrawing groups also
reacted with olefins to give good yields of the corresponding
ketones in the presence of 10. Compared with the reaction
performed in the absence of aniline, the intervention of trans-
imination was quite significant for a large enhancement of
reactivity.|| Both microwave equipments, domestic oven and
monomode reactor, allowed high reactivity.26
To check whether the other steps of the reaction, i.e. trans-
imination of 7b with 4, and subsequent hydroiminoacylation,
are also responsible for the observed specific microwave effect,
the microwave-assisted alkylation of 7b with olefins24 was con-
ducted. As shown in Table 5, aldimine 7b underwent Rh()-
catalyzed alkylation smoothly under microwave irradiation to
give corresponding ketones after hydrolysis. However, no sig-
nificant specific microwave effect was observed within 20 min at
140 ЊC, as similar yields were obtained from the control experi-
ments performed using monomode microwave reactor or
preheated oil bath (eqn. 3, Table 6, entry 1).
(3)
|| The hydroacylation did not occur in the absence of 2-amino-3-
picoline 4, which bears a coordination site and facilitates the C–H bond
activation, a key step of hydroacylation, by forming aldimine inter-
mediate 7a. The role of aniline (10), which has no coordination site, is
to facilitate the formation of aldimine intermediate 7a. Actually, when
the reaction of 1a and 2d was carried out under the same conditions
described in Table 4 (entry 5) but in the absence of 4, no hydroacylation
product was obtained. A chelation-assisted hydroacylation and the
essential role of 2-amino-3-picoline have been well documented (see ref.
13).
On the other hand, as previously shown in the case of the
hydroiminoacylation using aldimine 7a (Table 2), a specific
microwave effect could be observed by decreasing temperature
and/or reaction time (Table 6, entry 2 and 3).
This result certifies that the specific microwave effect origin-
ates from the condensation of aldehyde and 10, and it is the
rate-determining step of the reaction.
J. Chem. Soc., Perkin Trans. 1, 2002, 1280–1285
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standard. J values are given in Hz. 13C NMR spectra were
Table 5 Microwave-assisted alkylation of aldimine 7b with olefins 2
through transiminationa
recorded at 62.5 or 50 MHz. Infrared spectra were recorded
with a Nicolet Impact 400 spectrometer. GC analyses were
conducted using Donam DS 2000 Gas Chromatography. Mass
spectra were obtained using G1800A GCD System.
Entry
Olefin (2)
Product (6)
Isolated yield (%)
1
2
3
4
5
2a
2b
2c
2d
2e
6a
6b
6c
6d
6e
76
93
97
94
83
Typical procedure for the catalytic reaction using monomode
microwave reactor (method A)
Preparation of 1-phenylundecan-1-one (6a, eqn. 1). In a 10 cm3
Pyrex tube, were introduced successively benzaldehyde (1a, 160
mg, 1.4 mmol), 2-amino-3-picoline (4, 30 mg, 0.28 mmol), dec-
1-ene (2a, 980 mg, 7 mmol), (PPh3)3RhCl (3, 130 mg, 0.14
mmol) and benzoic acid (5, 34 mg, 0.14 mmol). The reaction,
which was followed by TLC, was carried out with external
mechanical stirring for 30 min to ensure homogeneous condi-
tions at 140 ЊC under microwave irradiation using monomode
reactor. After cooling, the reaction mixture was diluted with 10
cm3 of chloroform and washed with 2 × 10 cm3 of a 10%
sodium bisulfite solution. The organic layer was separated and
concentrated. The crude product was purified by flash column
chromatography (SiO2, n-pentane–ethyl acetate = 8 : 1) to afford
1-phenylundecan-1-one 6a (327 mg, 95%), which was identified
a The reactions were conducted in closed vessels using a domestic
microwave oven in the presence of 2 mol% of 3, 20 mol% of 4, and 10
mol% of 5 for 10 min.
Table 6 The hydroiminoacylation of dec-1-ene with aldimine 7b under
solvent-free conditions (eqn. 3)
Isolated yield
of 6a(%)
b
Entry
T /ЊC
t/min
MWa
∆
1
2
3
140
140
120
20
10
10
91
81
45
85
50
31
1
by NMR and GC-MS.30 Mp 28–30 ЊC δH (250 MHz, CDCl3,
Me4Si): 7.95 (2H, d, J 7.3), 7.5 (3H, m), 2.96 (2H, t, J 7.4), 1.73
(2H, m), 1.3–1.2 (14H, m) and 0.88 (3H, t, J 6.5); m/z (EI) 246
(Mϩ, 3%), 133 (11), 120 (100), 105 (95) and 77 (47).
Reactions under conventional heating were carried out with
exactly the same vessels and under similar conditions of time
and temperature (see Fig. 1 and Fig. 2) but inside a preheated
oil bath.
a MW = microwave irradiation. b ∆ = conventional heating.
Conclusion
As a promising way to prepare ketones from aldehydes, a
chelation-assisted hydroacylation of olefins was achieved under
microwave irradiation in a solvent-free protocol. The reactivity
of this reaction was largely improved with introducing a trans-
imination by means of adding aniline as well as 2-amino-3-
picoline. Various aldehydes and olefins were applied to this
protocol to afford corresponding ketones. Both domestic
microwave oven and monomode reactor effected the transform-
ation of aldehydes into ketones successfully. An important spe-
cific microwave effect was observed during the reaction within
10–30 min at 140 ЊC from comparison of the reactivity between
the conventional heating mode and the microwave activation
mode performed using monomode reactor, which permitted the
accurate control of microwave power and temperature. The
existence of specific microwave effect under these conditions
certifies that the rate-determining step of the overall reaction is
the initial condensation of amine and aldehyde, rather than the
subsequent transimination or hydroiminoacylation, where the
significant specific microwave effect could be observed only
under mild conditions.
Typical procedure for the catalytic reaction using multimode
domestic microwave oven (method B)
Preparation of 1-phenylheptan-1-one (6c, Table 1, entry 6). In
a 1 cm3 screw capped pressure vial, were charged 1a (21.2 mg,
0.200 mmol), 4 (8.6 mg, 0.080 mmol), hex-1-ene (2c, 84.2 mg,
1.00 mmol), 3 (9.2 mg, 0.010 mmol) and 5 (2.4 mg, 0.020
mmol). The reaction mixture was placed in a microwave oven
and heated for 10 min without stirring. The reaction mixture
was kept homogeneous throughout the reaction. After cooling,
the crude product was purified by column chromatography
(SiO2, n-hexane–ethyl acetate = 5 : 1) to give 1-phenylheptan-1-
one 6c (28.0 mg, 75%), which was identified by comparison with
authentic specimen commercially available.
Among the other products, ketones 6b,31 6d,32 6e,33 and 6g13d
are already known. All of the new compounds are character-
ized below.
1-(4-Methoxyphenyl)undecan-1-one 6f. Mp 51–52 ЊC δH (200
MHz, CDCl3, Me4Si): 7.9 (2H, d, J 9.0 Hz), 6.9 (2H, d, J 8.9),
4.1 (3H, s), 2.8 (2H, t, J 7.4 Hz), 1.7 (2H, m), 1.3–1.2 (14H, m)
and 0.8 (3H, t, J 6.3);δC (50 MHz, CDCl3, Me4Si): 198.42,
163.07, 129.99, 113.38, 55.03, 38.98, 31.76, 29.33, 24.37, 22.53
and 13.82; νmax(neat)/cmϪ1: 3089, 2917, 1679, 1603, 839 and 731;
m/z (EI) 276.2065 (MϩؒC18H28O2 requires 276.2089).
Experimental
Aldehydes and olefins used in the experiments were purchased
from commercial sources and purified by standard pro-
cedures.27 Aldimine such as benzylidene(3-methylpyridin-2-
yl)amine (7a) and benzylidene(phenyl)amine (7b) were pre-
pared under microwave activation by reacting benzaldehyde
with 2-amino-3-picoline or aniline using K10 clay as a catalyst
in dry conditions within 3 min (yields 95%) according to
Varma’s procedure.28 (PPh3)3RhCl (Wilkinson’s complex, 3)
was prepared as described in the literature.29 Either a multi-
mode domestic microwave oven (Samsung, RE-431H, 700 W)
or a monomode microwave reactor (Synthewave 402 from
Prolabo) was used for microwave irradiation. In the case of the
latter equipment, the microwave power can be modulated
between 15 and 300 W (2450 MHz), and an accurate control of
temperature at constant value can be achieved, while it is
impossible with the former due to non-homogeneous electro-
magnetic field owing to reflex of microwave on the oven
walls. 1H NMR spectra were recorded at 250 or 200 MHz. The
chemical shifts (δ) are reported in ppm relative to the internal
1-(4-Dimethylaminophenyl)undecan-1-one 6h. Mp 72–73 ЊC,
δH (200 MHz, CDCl3, Me4Si): 7.9 (2H, d, J 9.2), 6.6 (2H, d,
J 9.1), 3.0 (6H, s), 2.8 (2H, t, J 7.2), 1.7 (2H, m), 1.3–1.2 (14H,
m) and 0.8 (3H, t, J 6.4); δC(50 MHz, CDCl3, Me4Si): 198.5,
152.96, 129.98, 124.93, 110.36, 39.71, 37.68, 31.71, 29.26, 24.86,
22.49 and 13.93; νmax(neat)/cmϪ1: 2917, 1659, 1611, 820 and 795;
m/z (EI) 289.2436 (MϩؒC19H31NO requires 289.2406).
1-(4-Dimethylaminophenyl)-4-phenylbutan-1-one 6i. Mp 100–
101 ЊC δH (200 MHz, CDCl3, Me4Si): 7.9 (2H, d, J 9.0), 7.3 (5H,
m), 6.6 (2H, d, J 9.1), 3.0 (6H, s), 2.9 (2H, t, J 7.3), 2.7 (2H, t,
J 7.6) and 2.1 (2H, m); δC(50 MHz, CDCl3, Me4Si): 198.02,
153.25, 142.07, 130.19, 128.45, 125.85, 124.94, 110.62, 39.85,
1284
J. Chem. Soc., Perkin Trans. 1, 2002, 1280–1285

View Article Online
36.98, 35.44 and 26.43; νmax(neat)/cmϪ1: 3024, 2930, 1659, 1603
and 814. m/z (EI) 277.1661 (MϩؒC18H21NO requires 267.1623).
J. Org. Chem., 2000, 65, 4537; K. Olofsson, H. Sahlin, M. Larhed
and A. Hallberg, J. Org. Chem., 2001, 66, 544.
9 M. Larhed, G. Lindberg and A. Hallberg, Tetrahedron Lett., 1996,
37, 8219; M. Larhed, M. Hoshino, S. Hadida, D. P. Curran and
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8017.
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1980, 192, 257; T. B. Marder, D. C. Roe and D. Milstein,
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and references therein.
13 (a) C.-H. Jun, H. Lee and J.-B. Hong, J. Org. Chem., 1997, 62, 1200;
(b) C.-H. Jun, D.-Y. Lee and J.-B. Hong, Tetrahedron Lett., 1997, 38,
6673; (c) C.-H. Jun, J.-B. Hong and D.-Y. Lee, Synlett, 1999, 1;
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Ed., 2000, 39, 3070.
1-(4-Trifluoromethylphenyl)undecan-1-one 6j. Mp 46–47 ЊC
δH (200 MHz, CDCl3, Me4Si): 8.1 (2H, d, J 8.2), 7.7 (2H, d,
J 8.2), 3.0 (2H, t, J 7.3), 1.7 (2H, m), 1.3–1.2 (14H, m) and 0.9
(3H, t, J 6.5); δC(50 MHz, CDCl3, Me4Si): 198.85, 139.23,
133.46, 128.24, 125.50, 120.00, 37.74, 31.82, 29.36, 24.00, 22.59
and 13.93; νmax(neat)/cmϪ1: 2917, 1686, 1580, 863, and 833; m/z
(EI) 314.1894 (MϩؒC18H25F3O requires 314.1858).
1-(4-Trifluoromethylphenyl)-4-phenylbutan-1-one 6k. Mp 74–
75 ЊC δH (200 MHz, CDCl3, Me4Si): 8.0 (2H, d, J 8.2), 7.7 (2H,
d, J 8.2), 7.3 (5H, m), 3.0 (2H, t, J 7.2), 2.8 (2H, t, J 7.5) and 2.1
(2H, m); δC(50 MHz, CDCl3, Me4Si): 198.68, 141.32, 138.46,
133.46, 128.24, 125.91, 125.42, 120.39, 37.70, 34.88 and 25.28;
νmax(neat)/cmϪ1: 3028, 2952, 1688, 1603, 870, and 826; m/z (EI)
292.1078 (MϩؒC17H15F3O requires 292.1075).
Typical procedure for the alkylation of 7b using multimode
domestic microwave oven (Table 5, entry 3)
In a 1 cm3 screw capped pressure vial, were charged 7b (36.2 mg,
0.200 mmol), 4 (4.8 mg, 0.040 mmol), 2c (84.2 mg, 1.00 mmol),
3 (3.7 mg, 0.0040 mmol) and 5 (2.4 mg, 0.020 mmol). The reac-
tion mixture was placed in a microwave oven and heated for 15
min without stirring. After the reaction, the reaction mixture
was treated with 1 M HCl at rt for 6 h, then the mixture was
extracted with 10 cm3 of Et2O. The organic layer was dried over
MgSO4, and concentrated. The crude product was purified by
column chromatography (SiO2, n-hexane–ethyl acetate = 5 : 1)
to give 6c (37.0 mg, 97%).
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P. Jacquault, Prolabo company, European Patent 545995 AI, 21-12-
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This work was supported by the National Research Laboratory
(Organotransition Metal Catalysis Lab. 2000-N-NL-01-
C-271) Program administrated by the Ministry of Science
and Technology, and by Korean Science and Engineering
Foundation (20004010). Authors also acknowledge Brain
Korea 21 project.
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