Reductive dimerization and reduction of imines using lanthanum metal

Article abstract of DOI:10.1002/hc.10007

The treatment of N-benzylideneaniline (1a) with a half-equivalent of lanthanum metal and a catalytic amount of iodine gave the reductive dimerization product of 1a, a vic-diamine, in good yield. Various vic-diamines were synthesized from aldimines in this

Full text of DOI:10.1002/hc.10007

Heteroatom Chemistry
Volume 13, Number 2, 2002
Reductive Dimerization and Reduction
of Imines Using Lanthanum Metal
Toshiki Nishino, Yutaka Nishiyama, and Noboru Sonoda
Department of Applied Chemistry, Faculty of Engineering & High Technology Research Center,
Kansai University, Suita, Osaka 564–8680, Japan
Received 6 June 2001; revised 23 July 2001
which may be supplied during the change from
ABSTRACT: The treatment of N-benzylideneaniline
zero-valent metal to the stable trivalent ion, can be
(1a) with a half-equivalent of lanthanum metal and a
used directly in organic reactions, it is expected that
catalytic amount of iodine gave the reductive dimeri-
the organic chemistry using lanthanoid compounds
zation product of 1a, a vic-diamine, in good yield.
as reducing agents will be widely expanded. Hith-
Various vic-diamines were synthesized from aldimines
erto, the use of ytterbium [3], samarium [4], and
in this manner in moderate to good yields. Our find-
cerium [5] metals as agents in organic reactions
ings suggest that electrons of a zero-valent lanthanum
have been reported; however, efficient use of the elec-
metal were efficiently utilized in this reductive dimeri-
trons of the lanthanoid metal has been extremely lim-
zation. In the reaction of ketimines, however, a simi-
ited [6]. To establish a new method for the efficient
lar reductive dimerization did not take place, and the
use of the available electrons of lanthanum and re-
corresponding amines were formed as the sole prod-
lated metals, we examined first the use of lanthanum
C
ucts.
2002 Wiley Periodicals, Inc. Heteroatom Chem
metal itself, which has the largest redox potential
[7] and can be purchased at the cheapest price of
all lanthanoid metals [8]. We found that the reduc-
tive dimerization of aldimines with lanthanum metal
occurred, accompanied by the efficient transfer of
available electrons from the metal to the substrate
(Eq. (1)).
13:131–135, 2002; Published online in Wiley Interscience
(www.interscience.wiley.com). DOI 10.1002/hc.10007
INTRODUCTION
Lanthanoid metal salts and organolanthanoid com-
pounds have often been used in organic synthesis
[1]. In particular, low-valent lanthanoid species hav-
ing strong reducing ability, which were generated
in situ by the reaction of lanthanoids with various
reagents, have been widely used in organic synthe-
sis [2]. Since these reagents have already lost one or
two electrons of the zero-valent metal in the prepa-
ration step, before use as the reagent, these reduc-
tions usually required stoichiometric or an excess
amount of lanthanoid reagents to produce a good
yield of product by these methods. If three electrons,
RESULTS AND DISCUSSION
The treatment of N-benzylideneaniline (1a) with lan-
thanum metal was examined under various reac-
tion conditions and the results are listed in Table 1.
N-Benzilideneaniline (1a) was treated with lan-
thanum metal (1 equiv.) in THF at 67 C for 8 h;
however, reductive dimerization and/or reduction
products were not obtained and the starting material
was recovered (entry 1). We have already reported
Correspondence to: Yutaka Nishiyama; e-mail: nishiya@ipcku.
kansai-u.ac.jp.
2002 Wiley Periodicals, Inc.
c
131

132 Nishino, Nishiyama, and Sonoda
TABLE 1 Reaction of N-Benzylideneaniline (1a) with Lan-
thanum Metal under Various Reaction Conditions
Yield (%)a
(dl:meso)
Entry
1a (mmol)
La (mmol)
I2 (mmol)
1
2
3
4
2.0
2.0
2.0
2.0
2.0
4.0
2.0
1.0
–
0
0.8
0.4
0.2
87b (55:45)
87 (49:51)
178 (33:67)
aGC yield based on lanthanum being assumed to function as a one
electron donor atom. Parenthesis shows the ratio of dl and meso
determined by 1H NMR.
bGC yield based on imine.
that the addition of a catalytic amount of iodine dra-
matically enhances the reaction of carbonyl com-
pounds with lanthanum metal [9]. The reaction
was then carried out in the presence of 0.2 equiv.
of iodine, and the diamine (2a), the reductive cou-
pling product of 1a, was obtained in 87% yield
(entry 2) [10]. To determine the possibility of the
efficient use of several electrons present in a zero-
valent lanthanum metal, we examined the reaction
of 1a with a 0.5 equiv. of lanthanum metal. When
1a was allowed to react with a 0.5 equiv. amount
of lanthanum metal in the presence of a catalytic
amount of iodine, 2a was produced in 178% yield
(based on the presumption of only one electron be-
ing available from each atom of the lanthanum metal
used) (entry 4). This yield clearly proves that about
two electrons of the lanthanum metal were efficiently
utilized in this coupling reaction. In addition, the
diasteremeric ratio of the vic-diamine was affected
by the amount of lanthanum metal used. The reduc-
tive dimerization reaction using a 0.5 equiv. of lan-
thanum metal gave the meso-isomer preferentially
[12], and the dl-diamine was preferentially formed
with use of 2 equiv. of lanthanum metal (entries
2 and 4). Although, at the present time, we can-
not explain the reason why the diastereomeric ratio
was affected by the amount of lanthanum metal
used, the meso selectivity may be explained by con-
sideration of the reaction path, including the addi-
tion of the ketyl like intermediate 3, which was gen-
erated via the one electron transfer from lanthanum
metal to 1, to the carbon–nitrogen double bond of
another imine (Scheme 1) [13].
SCHEME 1
N-benzylideneanilines were treated with 0.5 equiv.
of lanthanum metal, the corresponding vic-diamines
were formed in moderate to good yields (entries 1,
2, 3, and 5). On the contrary, the reaction of an
N-benzylideneaniline derivative containing a strongly
electron withdrawing group such as a nitro did not
occur (entry 4). In the case of an N-alkyl substituted
aldimine, the yield of vic-diamine was very low be-
cause of various side reactions (entry 6).
Unlike aldimines, the reaction of N-diphenyl-
methyleneaniline (4a) with lanthanum metal did
not produce the dimerized product, but obtained
the reduction product, the amine 5a, in 82% yield
(entry 1 in Table 3). Ketimines 4b and 4c were also
TABLE 2 Reductive Dimerization of Various Aldimines with
Lanthanum Metal
Yield (%)a
(dl:meso)
Entry
Ar
R
1
2
3
4
5
6
p-MeC6H4
o-MeC6H4
p-MeOC6H4
p-NO2C6H4
C6H5
C6H5
C6H5
C6H5
C6H5
p-MeOC6H4
CH3
1b
1c
1d
1e
1f
154 (39:61)
125 (>99:<1)
125 (38:62)
n.r.
104 (39:61)
b
C6H5
1g
–
Various aldimines were allowed to react with a
0.5 equiv. of lanthanum metal in the presence of a
catalytic amount of iodine, and the results are shown
in Table 2. When methyl and methoxy substituted
aIsolated yield based on lanthanum being assumed to function as a
one electron donor atom. Parenthesis shows the ratio of dl and meso
determined by 1H NMR.
bVarious complex mixtures were formed.

Reductive Dimerization and Reduction of Imines Using Lanthanum Metal 133
TABLE 3 Reduction of Various Ketimines with Lanthanum
Metal
shown here provide a new way of using lanthanum
metal in organic synthesis.
Further studies on the utilization of lanthanum
metal in organic synthesis are now in progress.
EXPERIMENTAL
Instruments
Entry
Substrate
Time (h)
Yield (%)a
1H and 13C NMR spectra were recorded on a JEOL
JNM-GSX-400 (400 MHz) spectrometer using CDCl3
as a solvent with tetramethylsilane as the internal
standard. FT-IR spectra were obtained on a Perkin
Elmer Model PARAGON 1000 spectrophotometer.
Mass spectra were measured on a Shimadzu Model
QP-5050A instrument. Gas chromatography (GC)
was carried out on a Shimadzu GC-14A instrument
equipped with a flame ionizing detector and using a
capillary column (Hicap-CBP-1-S25-025, 0.25 mm
25 m).
1
8
82
2
3
8
82
48
24
Reagents
aIsolated yield based on ketimine.
Imines were prepared by the reaction of amines
with carbonyl compounds. Iodine and lanthanum
metal were commercially available high grade prod-
ucts and were used without purification. The other
reagents and solvents were purified by the usual
methods before use.
reduced by lanthanum metal to give the correspond-
ing amines in 82 and 48% yields, respectively (Ta-
ble 3). In order to better understand the reaction
pathway, when the reaction was quenched with D2O
instead of H2O, the amine 5a0, in which the deu-
terium atom was introduced onto the carbon atom,
was obtained in 86% yield (Eq. (2)).
General Procedure of the Reductive Dimerization
of Aldimines with Lanthanum Metal in the
Presence of a Catalytic Amount of Iodine
Lanthanum powder (139 mg, 1 mmol) was placed
in a three-necked flask. Iodine (51 mg, 0.2 mmol),
THF (2.5 ml.), and the aldimine (2 mmol) were added
to the flask, and the mixture was stirred at 67 C
for 8 h under a nitrogen atmosphere. The color of
the solution gradually darkened. After the reaction
was completed, methanol and silica gel were added
and the mixture was stirred for 0.5 h. The result-
ing mixture was filtered and the filtrate was concen-
trated. Purification of the residue by column chro-
matography on silica gel afforded the corresponding
vic-diamine. Products 2a [16] and 2b–d [17] were
characterized by comparison of their spectral data
with those of authentic samples. The structures of
the products were assigned by their 1H and 13C NMR
and IR spectra.
Fujiwara and co-workers have reported that the re-
action of 4a with Yb metal in the presence of a cat-
alytic amount of MeI gave 5a in a good yield [14].
In this work, they proposed that 5a was formed by
the hydrolysis of the Yb(II) N-diphenylmethylene-
aniline dianion. Recently, they succeeded in isolat-
ing the Yb(II) N-diphenylmethyleneaniline dianion
by the reaction of 4a with Yb metal in the presence
of HMPA [15]. We then assumed that the formation
of the amine as described above might occur through
a similar lanthanum intermediate.
General Procedure of the Reduction of Ketimines
with Lanthanum Metal in the Presence
of a Catalytic Amount of Iodine
We have found that lanthanum metal can be
used as an efficient reducing agent of imines in the
presence of a catalytic amount of iodine. The results
Lanthanum powder (278 mg, 2 mmol) was placed in
a three-necked flask. Iodine (102 mg, 0.4 mmol), THF

134 Nishino, Nishiyama, and Sonoda
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1
ucts were assigned by their H and 13C NMR and
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1,2-Diphenyl-N,N0-bis(4-methoxyphenyl) ethylene-
diamine (2f) (a mixture of dl and meso isomers). 1H
NMR : 3.64 (s, 6H, OCH3), 4.34 (br s, 2H, NH), 4.45
(s, 0.78H, CH), 4.87 (s, 1.22H, CH), 6.46–7.21 (m,
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128.9, 138.7, 140.8, 152.3; IR: 3379, 3060, 3028, 3003,
1
2947, 2832, 1510, 1242, 1035, 821, 756 cm .
N-Deuteriumdiphenylmethylaniline
(5a0). 1H
NMR : 4.18 (br s, 1H, NH), 6.49–7.34 (m, 15H,
Ar); 13C NMR : 62.5 (t), 113.4, 117.6, 127.3, 128.3,
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ACKNOWLEDGMENT
We thank the Santoku Co. for supplying the lantha-
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Reductive Dimerization and Reduction of Imines Using Lanthanum Metal 135
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