Efficient ruthenium catalyzed transfer hydrogenation of functionalized imines by isopropanol under controlled microwave heating

Article abstract of DOI:10.1139/v05-103

Transfer hydrogenation of various functionalized imines by isopropanol catalyzed by [Ru(CO)₂(Ph₄C₄CO)]₂ (3) has been studied. The use of either an oil bath or controlled microwave heating in toluene led to an ef

Full text of DOI:10.1139/v05-103

9
09
Efficient ruthenium catalyzed transfer
hydrogenation of functionalized imines by
isopropanol under controlled microwave heating
1
Joseph S.M. Samec, Laetitia Mony, and Jan-E. Bäckvall
Abstract: Transfer hydrogenation of various functionalized imines by isopropanol catalyzed by [Ru(CO) (Ph C CO)] (3)
2
4
4
2
has been studied. The use of either an oil bath or controlled microwave heating in toluene led to an efficient procedure
with high turnover frequencies and the product amines were obtained in high yields. An advantage with catalyst 3 over
the conventional [Ru (CO) (µ-H)(Ph C COHOCC Ph )] (1) is the absence of an initiation period, which results in a
2
4
4
4
4
4
faster reaction with 3 as compared to 1.
Key words: transfer hydrogenation, ruthenium, imines, microwave.
Résumé : On a étudié la réaction de transfert d’hydrogène, catalysée par le [Ru(CO) (Ph C CO)] (3), de l’isopropanol
2
4
4
2
vers diverses imines fonctionnalisées. L’utilisation d’un bain d’huile ou d’un chauffage par micro-ondes contrôlé dans
le toluène conduit à une méthode efficace impliquant des fréquences élevées de renouvellement et à des rendements
élevés en amines. Par rapport au catalyseur conventionnel [Ru (CO) (µ-H)(Ph C COHOCC Ph )] (1), le catalyseur (3)
2
4
4
4
4
4
ne présente pas de période d’initiation et il en résulte des vitesses de réaction plus rapides avec 3 par comparaison
avec 1.
Mots clés : hydrogénation par transfert, ruthénium, imines, micro-onde.
[
Traduit par la Rédaction] Samec et al. 916
Introduction
Several transition-metal complexes are known to catalyze
the transformation in eq. [1] with isopropanol or formic acid
as the hydrogen donor (6–8). Dimeric catalyst 1 (9)
The reduction of imines to amines is an important trans-
formation in organic synthesis since amines are useful build-
ing blocks for pharmaceuticals and other biologically active
compounds. In situ reduction of imines generated by the re-
action of ketones with an amine (reductive amination) is a
commonly used procedure (1). Although the latter protocol
works fine in many systems with various reducing agents
(
Scheme 1), which has frequently been employed in various
hydrogen transfer reactions (10, 11), was recently success-
fully used in our group for the transfer hydrogenation of im-
ines (8). Catalyst 1 is in equilibrium with monomers 2 and A
(
Scheme 1). The monomer 2 is able to hydrogenate a hydro-
gen acceptor, e.g., an imine, whereas the monomer A can
dehydrogenate a hydrogen donor, e.g., isopropanol. These
processes interconvert 2 and A. We recently showed that the
hydrogen transfer from 2 to a ketimine occurs in a stepwise
manner (12).
The active monomers 2 and A involved in the catalytic
hydrogen transfer of imines can also be generated from the
dimeric catalyst 3 (13). In the present work we studied the
use of catalyst precursor 3 in the hydrogen transfer of
functionalized imines.
The use of microwaves to accelerate catalytic reactions
has recently attracted attention (14, 15). With the employ-
ment of microwaves, the reaction times can be reduced con-
siderably and this is of great use when a larger number of
compounds are required (e.g., for screening). In this work
we have used microwave heating to lower the catalyst load-
(
2), it is often associated with low selectivity. Direct reduc-
tion of imines can be carried out with hydride reagents (3) or
with catalytic hydrogenation (4). More recently, transfer hy-
drogenation has been reported as a viable alternative for re-
duction of imines (eq. [1]) (5). The advantage of the latter
procedure is that the use of hydrogen gas is avoided and
that, e.g., isopropanol can be used as the hydrogen source.
The acetone thus produced is readily removed by distilla-
tion. The transfer hydrogenation protocol also shows a higher
functional group tolerance compared to hydride reagents.
R3
R3
N
Catalyst
HN
R1
[
1]
Hydrogen donor
R1
R2
R2
Received 4 January 2005. Published on the NRC Research Press Web site at http://canjchem.nrc.ca on 27 July 2005.
2
J.S.M. Samec, L. Mony, and J.-E. Bäckvall. Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-
1
06 91 Stockholm, Sweden.
1
This article is part of a Special Issue dedicated to Professor Howard Alper.
Corresponding author (e-mail: jeb@organ.su.se).
2
Can. J. Chem. 83: 909–916 (2005)
doi: 10.1139/V05-103
© 2005 NRC Canada

9
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Can. J. Chem. Vol. 83, 2005
Scheme 1.
CO
CO
Ph
O
O
Ph
Ru
Ph
Ph
Ph
Ph
Ph
H
H
O
Ru
Ph
Ph
OH Ph
O
K
2 H
Ph
Ph
Ru
Ph
Ru
diss
Ph
Ph
OC
OC
Ph
+
Ph
Ph
H
Ph
Ph
Ph
from
H-donor
Ru
Ph
Ph
Ru
O
CO
Ph
OC CO OC
OC
OC
OC
CO
1
2
8 e-
A
3
1
16 e-
Ph
3
2
Ph
Ph
OH
R
R
N
O
Ph
1
R
Ru
H
OC
OC
1
a
3
Ph
R
HN
Ph
OH
O
1
2
Ph
Ph
R
R
Ru
OC
OC
A
ing and reduce reaction times in the transfer hydrogenation
of imines to amines with catalyst 3.
Fig. 1. Comparison between precatalysts 1 and 3 in the transfer
hydrogenation of imine 6 in toluene-d at 70 °C with
8
isopropanol-d using 0.6 mol% catalyst. The conversion was
8
1
measured by H NMR.
Results and discussion
A few procedures for transfer hydrogenation of imines to
amines have previously been reported in the literature (6–8).
With the objective being to develop a more practical and
useful procedure for ruthenium catalyzed transfer hydroge-
nation of imines by isopropanol, we decided to study the ef-
fects of catalyst precursor and temperature.
Ru-catalyst (0.6 mol%),
8
Isopropanol-d (24 equiv.)
Ph
Ph
N
HN
Ph
8
Toluene-d , 70°C
Ph
6
15
8
7
6
5
0
0
0
0
Choice of the catalyst precursor
Complexes 1 and 3 are catalyst precursors for the hydro-
gen donor 2 and hydrogen acceptor A. To compare 1 and 3
as catalyst precursors they were prepared according to a pro-
cedure described by Casey et al. (13). Tetraphenylcyclo-
pentadienone and Ru (CO) were refluxed in MeOH to give
1
3
40
3
2
0
0
3
12
the Shvo dimer 1 or in heptane to give 3 (Scheme 2). The
products were collected by filtration and recrystallized to
give 1 and 3, respectively, in high yields (-90%).
10
0
0
5
10
15
Initial experiments run in an oil bath at 110 °C revealed
that catalyst 3 was more efficient than catalyst 1 in the trans-
fer hydrogenation of imines and gave shorter reaction times.
To obtain a more detailed comparison between the two cata-
lyst precursors we studied their kinetics in the transfer hy-
drogenation of imine 6. Thus, the transfer hydrogenation of
imine 6 by isopropanol-d in toluene-d catalyzed by 1 or 3
Time (min)
in Fig. 1. From these results, it is evident that catalyst pre-
cursor 1 has an initiation period of several minutes, whereas
catalyst precursor 3 is active immediately and results in 23%
conversion after 2 min. The time to reach 75% conversion
was 14 and 10 min for 1 and 3, respectively. During the first
8
8
1
3
was monitored by H NMR at 70 °C. The results are shown
3
Due to the low boiling point of isopropanol, the reactions were run at 70 °C to prevent overpressure in the NMR tube.
©
2005 NRC Canada

Samec et al.
911
Scheme 2.
O
Ph
Ph
CO
CO
Ph
O
Ru
Ph
Ph
Ph
Ph
Ph
OC
OC
Ph
Ph
Ph
Heptane
Ru
O
Ru (CO)
3
12
Ph
3
Methanol
O
O
Ph
Ph
Ph
Ph
H
Ph
Ru
Ph
Ru
H
Ph
Ph
CO
OC CO OC
1
–
1
2
(
(
min, the turnover frequency (TOF) was <30 h for 1
dure, the only workup is the removal of the solvents. The
products are then readily purified by distillation giving the
amines in high yield. For example, reduction of imines with
either an ester or an acetal functionality, which may cause
problems in metal hydride reductions (either during the reac-
tion or in work up) proceeded smoothly with the present
method (Table 1, entries 2, 3, and 7).
–
1
–1
<15 h per ruthenium atom), whereas it was 1150 h for 3
575 h per ruthenium atom). Because of the higher effi-
ciency of 3 over 1, the former catalyst was chosen for fur-
–
1
ther studies.
Transfer hydrogenation of imines under thermal
heating
In our previously reported procedure for transfer hydroge-
nation of various imines by 1 using 24 equiv. of wet iso-
propanol in benzene at 70 °C, electron-deficient imines had
long reaction times (8). For increased efficiency, it was de-
sirable to shorten the reaction times and also to lower the
catalyst loading. An increase in temperature would lead to
shorter reaction times but it may also decrease the selectiv-
ity. With the aim to increase the efficiency of the reaction,
the transfer hydrogenation of model substrate 6 by catalyst
precursor 3 in isopropanol–toluene at 110 °C was studied.
The increase in temperature led to an efficient transfer hy-
drogenation of 6 where the catalyst loading could be de-
creased 10 times compared to our previous study (8). This
prompted us to study the electron-deficient imine 11, which
required 8 h at 70 °C in benzene. In the present system,
imine 11 had reached full conversion within an hour with the
same catalyst loading. The present system can also transfer
hydrogenate the very electron-deficient imine 14 bearing a
pyridyl group. To further extend this protocol and make it an
attractive alternative in organic synthesis, we decided to
study the transfer hydrogenation of imines having functional
groups that make them difficult to reduce to amines. It was
found that the present procedure tolerates various functional
groups such as esters, amines, ethers, acetals, and olefins
Transfer hydrogenation under controlled microwave
heating
Recently, we showed that the hydrogen transfer from the
active catalyst 2 to the imine is not concerted as previously
proposed (13), but stepwise (12). In the latter study, we
found that microwave irradiation was superior to conven-
tional oil bath heating for the generation of the active spe-
cies 2 from precursor 3 in a H atmosphere (Scheme 3).
2
Where conventional oil bath heating took several hours and
with unsatisfactory results, the microwave-promoted genera-
tion of active species 2 was very efficient. Active species 2
can be generated in a minute at 180 °C using microwave ir-
radiation, but with somewhat unreliable results. We found
that decreasing the temperature to 120 °C and prolonging
the reaction time to 20 min resulted in complete conversion
of 3 to 2 with full reproducibility (12).
Initial attempts to perform transfer hydrogenation of
imine 6 by precursor 3 in isopropanol and toluene with mi-
crowave irradiation gave unreliable results. For example,
when imine 6 was run with low catalyst loading (0.03–
0.06 mol%) at 110 °C, the results were difficult to repro-
duce. Increasing the catalyst loading slightly (to 0.1 mol%)
gave a smooth transfer hydrogenation of imine 6 to amine
15 within 20 min (Table 2, entry 1). Next, it was of interest
to find out if functionalized imines tolerate the transfer hy-
drogenation with microwave irradiation. We were pleased to
find that employing microwave irradiation improved the re-
duction in most cases even though there were two excep-
tions: imines 6 and 7 (Table 2, entries 1 and 2) needed
(
Table 1, entries 2–5, 7, and 8). In conventional reductions
using metal hydrides, the workup protocol includes tedious
extractions in the presence of strong acids and (or) bases,
which not only lowers the yield of the reactions, but also
lowers the functional group tolerance. In the present proce-
©
2005 NRC Canada

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Can. J. Chem. Vol. 83, 2005
Table 1. Transfer hydrogenation of different amines by wet isopropanol in toluene using 3.a
Catalyst
loading
Yield
Entry
1
Imine
Amine
Time (min)
b
(%)
(mol%)
N
NH
0.03
90
60
93
6
1
5
MeO
MeO
MeO
N
NH
2
0.06
93
95
MeOOC
MeOOC
7
16
MeO
N
NH
COOEt
3
4
5
0.06
0.3
60
60
COOEt
8
1
7
N
N
c
>99
N
N
H
9
18
MeO
MeO
N
NH
0.3
150
97
O
O
1
0
19
N
NH
c
6
1
60
>99
1
1
F
20
F
MeO
MeO
N
NH
7
8
3
3
60
60
95
96
OMe
OMe
OMe
1
2
21 OMe
MeO
MeO
N
NH
1
3
22
MeO
MeO
N
NH
9
3
240
96
1
4
2
3
N
N
a
The reactions were carried out using imine (1.0 mmol), catalyst 3 (0.003–0.03 mmol), and isopropanol (24 mmol, 1.85 mL) in
1
toluene (3.15 mL) at 110 °C. Full conversion was measured by H NMR.
b
Isolated yield unless otherwise noted.
c
1
Yield determined by H NMR.
higher catalyst loading in the microwave-assisted transfer
hydrogenation than by conventional heating. Except for
these examples, the general trend was shorter reaction times
and 13, which needed 3 mol% of catalyst loading and
60 min with conventional oil bath heating, only needed
0.5 mol% of the catalyst and were over within 10 min in the
microwave-assisted transfer hydrogenation (Table 2, entries
5 and 6). With these two imines, the efficiency is increased
by a factor of 36 times. With microwave irradiation, the re-
action time was reduced 12 times (from 240 to 20 min) for
the electron-deficient imine 14 (Table 2, entry 7).
(
10–20 min) and lower catalyst loading (0.1–0.5 mol%). For
example, imine 10, which needed 0.3 mol% of the catalyst
and 150 min using oil bath heating, was finished within
2
4
0 min with only 0.1 mol% of the catalyst (Table 2, entry
). This is an increase of >20 times in efficiency. Imines 12
©
2005 NRC Canada

Samec et al.
913
Scheme 3.
CO
CO
Ph
Ru
Ph
O
Ph
Ph
OH
Ph
Ru
Ph
2 H2
Ph
Ph
OC
OC
Ph
2
Ph
Ph
O
o
THF,120 C
Ru
H
OC
Ph
Microwave
OC
3
Table 2. Transfer hydrogenation of functionalized imines by 3 in wet isopropanol – toluene using microwave
irradiation.a
Catalyst
loading
Entry
1
Imine
Amine
Time (min) Yieldb
(
mol%)
N
NH
0.1
20
20
98
99
6
1
5
MeO
MeO
N
NH
2
0.5
MeOOC
MeOOC
7
16
MeO
MeO
MeO
MeO
N
NH
COOEt
3
4
0.5
0.1
10
20
99
94
COOEt
8
1
7
MeO
MeO
N
NH
O
O
1
0
19
N
NH
5
6
0.5
0.5
10
10
98
95
OMe
OMe
1
2
OMe
21 OMe
MeO
MeO
N
NH
1
3
22
MeO
MeO
N
NH
7
3
20
98
1
4
2
3
N
N
a
The reactions were run using imine (0.3 mmol), 3 (0.0003–0.009 mmol), toluene (1.9 mL), isopropanol (1.1 mL) under mi-
crowave irradiation for 20 min (110 °C, 2 bar (1 bar = 100 kPa)).
b
1
The yield was determined by H NMR.
Conclusions
tional groups, not compatible with conventional metal hy-
dride reduction, are readily reduced with low catalyst load-
ing and short reaction times to give high yields of the
corresponding amines. The use of controlled microwave ir-
We have developed an efficient transfer hydrogenation
protocol for imines. Imines bearing acid-or base-labile func-
©
2005 NRC Canada

9
14
Can. J. Chem. Vol. 83, 2005
radiation led to an efficient procedure where most imines
were reduced in greater than 90% yield within 20 min em-
ploying 0.1–0.5 mol% of catalyst. This procedure should be
a useful complement to existing methods for the reduction
of imines to amines.
was precipitated from CH Cl –pentane to yield 2.6 g (55%)
of white crystals. Spectral data were in accordance with
those previously reported in the literature (17).
2
2
N-Phenyl-[1-(4-fluorophenyl)ethylidene]amine (11)
The title compound was made according to the literature
procedure (8).
Experimental section
General methods
1H (400 or 300 MHz) and 13C (100 or 75 MHz) NMR
spectra were recorded on a Varian Mercury spectrometer.
Chemical shifts (δ) are reported in ppm, using residual sol-
vent as the internal standard, and coupling constants (J) are
given in Hz. Unless otherwise noted, all materials were ob-
tained from commercial suppliers and used without further
purification. Toluene was distilled from sodium benzophe-
none and isopropanol was distilled from CaO before use. All
other chemicals were used as received. Short-path distilla-
tions were conducted in a Büchi glass oven B-580. Elemen-
tal analyses were performed by Analytische Laboratorien,
Lindlar, Germany. Ruthenium complexes 1 and 3 were made
according to literature procedures (13).
(2,2-Dimethoxy-1-methylethylidene)-(4-methoxyphenyl)-
amine (12)
Anisidine (2.47 g, 20 mmol), dimethoxy acetone (3.94 g,
0 mmol), activated molecular sieves (4 Å, 7 g), and ben-
3
zene (10 mL) were added to a round-bottomed flask and
stirred at room temperature overnight. Yield: 4 g (90%) of a
1
colorless oil. H NMR (400 Hz, CDCl , 25 °C) δ: 1.83 (s,
3
3
1
2
2
H, CH ), 3.49 (s, 6H, OCH ), 3.80 (s, 3H, OCH ), 4.65 (s,
3 3 3
H, CH), 6.72 (m, 2H, aryl of p-methoxyphenyl), 6.88 (m,
1
3
H, aryl of p-methoxyphenyl). C NMR (100 Hz, CDCl3,
5 °C) δ: 13.9 (CH ), 55.1 (OCH ), 55.4 (OCH ), 107.6
CH), 114.2 (aryl of p-methoxyphenyl), 120.7 (aryl of p-
3
3
3
(
methoxyphenyl), 142.9 (aryl of p-methoxyphenyl), 156.3
C=N), 168.2 (aryl of p-methoxyphenyl). Elemental anal.
calcd. for C H NO (223.27) (%): C 64.55, H 7.68, N
(
N-Phenyl-(1-phenylethylidene)amine (6)
This compound was made according to literature proce-
dure (8).
1
2
17
3
6
.28; found: C 64.32, H 7.56, N 6.41.
N-(6-Methyl-2-hept-5-enylidene)-4-anisidine (13)
N-(4-Methoxyphenylimino)phenylacetic acid methyl
ester (7)
Anisidine (2.47 g, 20 mmol), 6-methyl-5-hepten-2-one
3 mL, 20 mmol), activated molecular sieves (4 Å, 7 g), and
(
Anisidine (2.46 g, 20 mmol), methylphenyl glyoxylate
benzene (10 mL) were added to a round-bottomed flask and
stirred at room temperature overnight. Yield: 2.74 g (59%)
of a yellow oil. Spectral data were in accordance with those
previously reported in the literature (18).
(
13 g, 80 mmol), activated molecular sieves (4 Å, 7 g), and
toluene (10 mL) were added to a round-bottomed flask and
stirred at room temperature overnight. The reaction mixture
was filtered through Celite, the filtrate evaporated, and the
crude product was precipitated from CH Cl –pentane. Yield:
2
2
1
3
g (50%) of yellow-brownish crystals. H NMR (400 Hz,
N-(4-Methoxyphenyl)-N-[(E)-1-(3-pyridyl)methyl-
idene]amine (14)
CDCl , 25 °C) δ: 3.69, (s, 3H, COOCH ), 3.81 (s, 3H,
3
3
OCH ), 6.87–6.96 (m, 2H, aryl of p-methoxyphenyl), 6.97–
3
Anisidine (2.46 g, 20 mmol), 3-pyridinecarboxaldehyde
2.67 g, 25 mmol), activated molecular sieves (4 Å, 7 g), and
7
.01 (m, 2H, aryl of p-methoxyphenyl), 7.45–7.50 (m, 3H,
(
1
3
phenyl), 7.84–7.86 (m, 2H, phenyl). C NMR (100 Hz,
benzene (5 mL) were added to a round-bottomed flask and
stirred at room temperature overnight. The reaction mixture
was filtered through Celite and the filtrate was evaporated.
The starting material was removed by bulb-to-bulb distilla-
tion (120 °C, 1 mbar, 1 bar = 100 kPa) and the product was
subsequently distilled (160 °C, 1 mbar). Yield: 3.8 g (90%)
of yellow crystals. Spectral data were in accordance with
those previously reported in the literature (17).
CDCl , 25 °C) δ: 51.9 (CH of ester), 55.4 (OCH ), 114.2
3
3
3
(
1
aryl of p-methoxyphenyl), 121.1 (aryl of p-methoxyphenyl),
27.8 (phenyl), 128.7 (phenyl), 131.5 (phenyl), 134.1
(
phenyl), 143.1 (aryl of p-methoxyphenyl), 157.3 (aryl of p-
methoxyphenyl), 159.1 (C=N), 166.1 (C=O).
Ethyl [N-(p-Methoxyphenyl)imino]acetate (8)
Anisidine (2.46 g, 20 mmol), ethyl glyoxalate (4 mL,
3
0 mmol), activated molecular sieves (4 Å, 7 g), and ben-
zene (5 mL) were added to a round-bottomed flask and
stirred at room temperature overnight. Spectral data were in
accordance with those previously reported in the literature
Screening catalysts
Catalyst 1 (1 mg, 1 µmol) or 3 (1 mg, 1 µmol) dissolved
in toluene-d (0.48 mL) was added to imine 6 (0.15 mmol)
8
(
16).
in a vial. The mixture was transferred to a NMR tube and
isopropanol-d (0.28 mL, 3.7 mmol) was added. The NMR
8
N-[1-(2-Furyl)methylidene]-N-(4-methoxyphenyl)amine
10)
Anisidine (2.46 g, 20 mmol), furfural (2.4 g, 25 mmol),
activated molecular sieves (4 Å, 7 g), and benzene (5 mL)
were added to a round-bottomed flask and stirred at room
temperature overnight. The reaction mixture was filtered
through Celite, the filtrate evaporated, and the crude product
tube was subsequently shaken and inserted into a prewarmed
(70 °C) spectrometer. After initial locking and shimming
(~2 min), acquisitions were acquired every minute. The re-
(
1
actions were followed by H NMR to ~75% conversion fol-
lowing the appearance of the methyl group of the amine at
δ 1.48 and the disappearance of the methyl group of the
imine at δ 2.24.
©
2005 NRC Canada

Samec et al.
915
General procedure for the transfer hydrogenation
under thermal heating — N-Phenyl-1-phenylethylamine
N-(2,2-Dimethoxy-1-methylethyl)-4-methoxy-
phenyl)amine (21)
(
15)
In a typical experiment, imine 6 (0.195 g, 1.0 mmol), cat-
alyst 3 (0.33 mg, 0.3 µmol), toluene (3.15 mL), isopropanol
1.84 mL, 24.0 mmol), and water (42 µL, 1% w/w) were
added to a 10 mL Schlenk tube and heated to 110 °C for
0 min. Solvents were evaporated in vacuo and the product
The general procedure was followed by using imine 12
(0.223 g, 1.0 mmol) and 3 (33 mg, 30 µmol). The product
was bulb-to-bulb distilled (250 °C, 0.5 mbar) to afford
1
(
amine 21 (0.202 g, 95%). H NMR (400 Hz, CDCl3, 25 °C)
δ: 1.15 (d, 2H, J = 6.6 Hz, CH3), 3.44 (s, 3H, OCH3), 3.47
(s, OCH3), 3.53–3.56 (m, 1H, CH), 3.74 (s, 3H, OCH3 of p-
methoxyphenyl), 4.27 (d, 1H, J = 3.8 Hz, acetal), 6.60–6.62
(m, 2H, aryl of p-methoxyphenyl), 6.76–6.78 (m, 2H, aryl of
9
was purified by distillation (250 °C, 0.5 mbar) to afford
amine 15 (0.182 g, 93%). Spectral data were in accordance
with those previously reported in the literature (19).
1
3
p-methoxyphenyl). C NMR (100 Hz, CDCl3, 25 °C) δ:
1
4.6 (CH ), 51.6 (CH), 55.5 (OCH ), 55.7 (OCH ), 56.5
3
3
3
(
1
OCH ), 107.1 (CH), 114.9 (aryl of p-methoxyphenyl),
15.2 (aryl of p-methoxyphenyl), 141.3 (aryl of p-
3
(
(
4-Methoxyphenylamino)phenylacetic acid methyl ester
16)
methoxyphenyl), 152.2 (aryl of p-methoxyphenyl). Elemen-
The general procedure was followed by using imine 7
1.9 mmol, 0.5 g), 3 (1.1 µmol, 1 mg), toluene (8 mL), and
tal anal. calcd. for C H NO (225.29) (%): C 63.97, H
8.50, N 6.22; found: C 63.74, H 8.39, N 6.35.
1
2
19
3
(
wet isopropanol (3.5 mL, 48.0 mmol). The product was dis-
tilled (250 °C, 0.5 mbar) to afford amine 16 (0.48 g, 93%).
Spectral data were in accordance with those previously re-
ported in the literature (20).
N-(6-Methyl-2-hept-6-enyl)-4-methoxyaniline (22)
The general procedure was followed using imine 13
0.136 g, 1.0 mmol) and 3 (22.5 mg, 20.8 µmol). The prod-
(
uct was bulb-to-bulb distilled (250 °C, 0.5 mbar) to afford
amine 22 (0.147 g, 96%). Spectral data were in accordance
to those previously reported in the literature (18).
N-(4-Methoxyphenyl)glycine ethyl ester (17)
The general procedure was followed by using imine 8
(
0.21 g, 1.0 mmol) and 3 (0.65 mg, 0.6 µmol). The product
was bulb-to-bulb distilled (200 °C, 0.5 mbar) to afford
amine 17 (0.199 g, 95%). H NMR (400 Hz, CDCl , 25 °C)
δ: 1.27 (t, 3H, J = 7.1 Hz, CH ), 3.74 (s, 3H, OCH ), 3.86 (s,
2
aryl of p-methoxyphenyl), 6.77–6.81 (m, 2H, aryl of p-
methoxyphenyl). C NMR (100 Hz, CDCl , 25 °C) δ: 14.4
(
4-(Methoxyphenyl)pyridin-3-ylmethylamine (23)
1
The general procedure was followed using imine 14
(0.212 g, 1.0 mmol) and 3 (33 mg, 30 µmol). The product
was bulb-to-bulb distilled (250 °C, 0.5 mbar) to afford
3
3
3
H, CH ), 4.23 (q, 2H, J = 7.1 Hz, CH ), 6.57–6.60 (m, 2H,
2
2
1
amine 23 (205.9 mg, 96%). H NMR (400 Hz, CDCl3,
1
3
25 °C) δ: 3.74 (s, 3H, OCH p-methoxyphenyl), 4.32 (s, 2H,
3
3
CH ), 47.0 (CH), 55.9 (OCH ), 61.4 (OCH ), 114.6 (aryl of
CH ), 6.58–6.61 (m, 2H, aryl of p-methoxyphenyl), 6.76–
3
3
3
2
p-methoxyphenyl), 115.1 (aryl of p-methoxyphenyl), 141.5
aryl of p-methoxyphenyl), 152.8 (aryl of p-methoxyphenyl),
71.6 (C=O of ester).
6.79 (m, 2H, aryl of p-methoxyphenyl), 7.26–7.29 (m, 1H,
(
1
pyridyl), 7.71–7.73 (m, 1H, pyridyl), 8.51–8.52 (m, 1H,
1
3
pyridyl), 8.62–8.63 (m, 1H, pyridyl). C NMR (100 Hz,
CDCl , 25 °C) δ: 46.7 (CH ), 55.8 (OCH ), 114.5 (aryl of p-
3
2
3
methoxyphenyl), 114.9 (aryl of p-methoxyphenyl), 122.3
Decahydropyrimido[1,2-␣]azepine (18)
(
pyridyl), 134.6 (pyridyl), 141.7 (aryl of p-methoxyphenyl),
48.5 (pyridyl), 149.0 (pyridyl), 154.9 (aryl of p-
methoxyphenyl). Elemental anal. calcd. for C H N O
Imine 9 (0.3 mmol, 45 µL), 3 (0.92 µmol, 1 mg), toluene-
1
d (0.95 mL), and isopropanol-d (0.55 mL, 7.2 mmol) were
8
8
1
3
14
2
added to a 10 mL Schlenk tube and heated to 70 °C for
(
6
214.27) (%): C 72.87, H 6.59, N 13.08; found: C 73.11, H
.72, N 13.21.
1
6
0 min. According to the H NMR there was full conversion.
The spectral data were in accordance with those previously
reported in the literature (21).
General procedure for the transfer hydrogenation of
imines under controlled microwave heating — N-
Phenyl-1-phenylethylamine (15)
Furan-2-ylmethyl(4-methoxyphenyl)amine (19)
In a typical experiment, imine 6 (58.6 mg, 0.3 mmol), 3
The general procedure was followed using imine 10
(
0.3 mg, 0.3 µmol), toluene (1.9 mL), isopropanol (1.1 mL),
(
0.171 g, 1.0 mmol) and 3 (2.8 µmol, 3 mg). The product
and water (25 µL, 1%) were charged into a Pyrex tube
was bulb-to-bulb distilled (250 °C, 0.5 mbar) to afford
amine 19 (0.167 g, 97%). The spectral data were in accor-
dance with those previously reported in the literature (17).
(
(
5 mL) fitted with a screw cap with a silicone–teflon septum
Personal Chemistry AB, Uppsala, Sweden). The septum
was closed and the vessel inserted into a microwave oven.
The microwave was run for 20 min (110 °C, 2 bar). The sol-
N-Phenyl-1-(4-fluorophenyl)ethylamine (20)
The general procedure was followed using imine 11
vents were evaporated, CDCl (0.7 mL) was added, and the
3
1
solution was transferred to an NMR tube and analyzed by H
(
64 mg, 0.3 mmol) and catalyst 3 (3.2 mg, 3 µmol), iso-
NMR, which showed 98% yield integrating the doublet at
δ 1.48 (CH3) of the amine and the singlet at δ 2.24 (CH3) of
the imine.
propanol (0.55 mL, 7.2 mmol), and 0.95 mL of toluene. Af-
ter 1 h, the sample was cooled down and analyzed by H
1
NMR. Conversion was >99%. Spectral data were in accor-
dance to those previously reported in the literature (8).
Amines 16–23 were prepared from the corresponding
imines (0.3 mmol) according to the general procedure for
©
2005 NRC Canada

9
16
Can. J. Chem. Vol. 83, 2005
transfer hydrogenation under microwave heating using 3
0.3–9 µmol). The results are given in Table 2.4
7. (a) N. Uematsu, A. Fujii, S. Hashiguchi, T. Ikariya, and R.
Noyori. J. Am. Chem. Soc. 118, 4916 (1996); (b) J. Mao and
D.C. Baker. Org. Lett. 1, 841 (1999).
(
8
9
. J.S.M. Samec and J.-E. Bäckvall. Chem. Eur. J. 8, 2955 (2002).
. Y. Blum, D. Czarkie, Y. Rahamim, and Y. Shvo. Organo-
metallics, 4, 1459 (1985).
Acknowledgments
We thank the Swedish Research Council for financial sup-
port. Laetitia Mony thanks the Ecole Normale Supérieure for
financial support.
10. (a) N. Menashe and Y. Shvo. Organometallics, 10, 3885
(1991); (b) M.L.S. Almeida, M. Beller, G.-Z. Wang, and J.-E.
Bäckvall. Chem. Eur. J. 2, 1533 (1996); (c) G. Csjernyik, A.H.
Éll, L. Fadini, B. Pugin, and J.-E. Bäckvall. J. Org. Chem. 67,
1
657 (2002); (d) J.H. Choi, N. Kim, Y.J. Shin, J.H. Park, and
J. Park. Tetrahedron Lett. 45, 4607 (2004).
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4
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©
2005 NRC Canada