Catalytic hydrogenation of α-iminophosphonates as a method for the synthesis of racemic and optically active α-aminophosphonates

Article abstract of DOI:10.1002/adsc.200700466

It was shown that the catalytic hydrogenation of α-iminophosphonates by molecular hydrogen can serve as a convenient method for the synthesis of racemic and optically active α-aminophosphonates. Up to 94% ee was achieved in the rhodium-catalyzed enantiose

Full text of DOI:10.1002/adsc.200700466

FULL PAPERS
DOI: 10.1002/adsc.200700466
Catalytic Hydrogenation of a-Iminophosphonates as a Method for
the Synthesis of Racemic and Optically Active a-Aminophospho-
nates
Nataliya S. Goulioukina,a,* Grigorii N. Bondarenko,a Sergey E. Lyubimov,b
Vadim A. Davankov,b Konstantin N. Gavrilov,c and Irina P. Beletskayaa,*
a
Department of Chemistry, Moscow State University, Leninskie Gory, GSP-2, Moscow 119992, Russia
Fax : (+7)-495-939-1854; e-mail: goulioukina@org.chem.msu.ru or beletska@org.chem.msu.ru
Institute of Organoelement Compounds, Russian Academy of Sciences, 28 Vavilov str., Moscow 119991, Russia
b
Fax : (+7)-495-135-6471
Department of Chemistry, Ryazan State University, 46 Svoboda str., Ryazan 390000, Russia
c
Fax : (+7)-0912-775-498
Received: September 21, 2007; Revised: December 6, 2007; Published online: February 6, 2008
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: It was shown that the catalytic hydrogena- catalyzed enantioselective hydrogenation using chiral
tion of a-iminophosphonates by molecular hydrogen ligand (R)-BINAP.
can serve as a convenient method for the synthesis
of racemic and optically active a-aminophospho- Keywords: a-aminophosphonates; asymmetric catal-
nates. Up to 94% ee was achieved in the rhodium- ysis; hydrogenation; a-iminophosphonates
Introduction
found to exhibit antifungal activity,[16] to be potent in-
hibitors of phenylalanine ammonia-lyase,[17] human
a-Aminophosphonic acids are among the most inten- prostatic acid phosphatase,[18] as well as promising
sively studied classes of biologically active com- structural units for the design of antithrombotic tri-
pounds.[1] A wide range of possibilities of practical use peptides.[19]
of a-aminophosphonates has stimulated considerable
Optically active a-aminobenzylphosphonic acids
interest in the development of methods for their syn- are of special interest. For instance, it was shown that
thesis. Much experimental material, which is summar- (+)-a-amino-3,4-dichlorobenzylphosphonic acid in-
ized in the monograph[1] and reviews,[2–6] has been ac- hibits phenylalanine ammonia-lyase almost forty
cumulated in this area. Considerable recent attention times more efficiently than its laevorotatory enantio-
has been focused on the most straightforward ap- mer.[17] Optically active substituted a-aminobenzyl-
proach to a-aminophosphonates based on the rhodi- phosphonates are used as chiral eluents for enantio-
um- and ruthenium-catalyzed hydrogenation (first of meric analysis of amino acids by ligand-exchange
all, enantioselective[7–14]) of the corresponding olefinic chromatography.[20]
precursors, and excellent results have been achieved.
Possibilities of hydrogenation of prochiral a-C=N-
Nevertheless, the limitation of this method is evident, unsaturated precursors for the synthesis of optically
as it cannot be used for the synthesis of a-aminophos- active a-aminophosphonic acids remained largely un-
phonic acids containing a quaternary b-carbon atom, explored until recently. Only a few examples of the
for instance, a-aminobenzylphosphonic or a-amino- catalytic enantioselective hydrophosphorylation of
2,2,2-trifluoroethylphosphonic acids. Both latter types Schiffꢀs bases in the presence of quinine,[21] an optical-
are particularly interesting. By analogy to aminocar- ly active thiourea derivative,[22] a chiral Brønsted acid,
boxylic acids, the introduction of fluorine atoms into derived from (R)-BINOL,[23] heterobimetallic BINOL
the molecule of aminophosphonic acids can extend complexes,[24] and the aluminum complex containing
the spectrum of their biological activity and make an [ONN(Me)O] tetradentate ligand of the hybrid
possible the application of 19F NMR spectroscopy to salane/salene type[25] were described. The purpose of
study the metabolism of these substances.[15] Some the present work is to develop new methods for the
ring-substituted a-aminobenzylphosphonic acids were synthesis of racemic and optically active esters of a-
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Synthesis of Racemic and Optically Active a-aminophosphonates
FULL PAPERS
aminophosphonic acids by the catalytic reduction of atom. Indeed, in the 31P NMR spectrum the signal of
the corresponding a-iminophosphonates.
the major isomer at 3.4 ppm is shifted upfield relative
to the signal of the minor isomer by 3.5 ppm (the
ratio of integral intensities is 96/4). Intense signals of
the methyl protons and carbon atoms of the tert-butyl
fragment of both isomers are well discernible in the
Results and Discussion
Diethyl a-iminomethylphosphonates containing aryl, 1H and 13C NMR spectra of a-iminophosphonate 2g;
heteroaryl, tert-butyl, and trifluoromethyl residues in their chemical shifts for the major Z-isomer are dH =
the a-position were chosen as model substrates. To 1.36 ppm and dC =27.9 ppm. For the minor E-isomer
avoid possible 1,3-prototropic rearrangements,[26,27] the resonances of the same nuclei exhibit upfield
phenyl and p-anisyl groups were used as substituents shifts to 1.30 and 27.5 ppm, respectively.
at the nitrogen atom. The p-anisyl protective group
A similar pattern of the signals is also observed for
can be removed by the action of cerium ammonium diethyl 1-(p-anisylimino)-2,2,2-trifluoroethylphospho-
nitrate; this procedure is well established and used in nate (2h), although with a substantial decrease in the
the chemistry of aminophosphonic acids.[28–30]
selectivity: the ratio of the Z- and E-isomers is 88/12.
For a-iminophosphonates 2a–f containing an aro-
The starting diethyl a-iminophosphonates 2a–h
were synthesized via the Arbuzov reaction of triethyl matic fragment in the a-position, the 31P NMR reso-
phosphite with the corresponding imidoyl chlorides nance of the major isomer is observed at 6.4–7.2 ppm.
1a–h (for the synthesis see Experimental Section) The signal of the minor isomer exhibits an upfield
similarly to a described procedure[31] (Scheme 1). The shift of 1.6–2.9 ppm. Simultaneously in the H and
1
reaction takes place upon heating at 120–1708C for 13P NMR spectra the upfield shift is observed for the
2–3 h; preparative yields of the target products 2a–d, triplets of the methyl protons (Dd=0.22–0.29 ppm)
f–h are 56–98%. Noticeable tarring of the reaction and signals of the methylene (Dd=1.1–1.2 ppm) and
mixture was observed only in the case of imidoyl methyl (Dd=0.3–0.4 ppm) carbon atoms of the dieth-
chloride 1e containing the furyl fragment, and diethyl oxyphosphoryl groups of the minor isomers. These
(p-anisylimino)
ACHTREUNG
isolated in 36% yield.
Six (2b–g) of the eight thus prepared a-imino- oxyphosphoryl group experiences the shielding effect
phosphonates are novel compounds, which we have of the aromatic N-substituent. Anisotropy of the aryl
completely characterized spectrally. The 31P NMR a-substituent in compounds 2b–d results in the upfield
spectra of all synthesized a-iminophosphonates 2a–h shift of signals of the methyl group of the p-anisyl
contain two signals, indicating the formation of Z- substituent at the nitrogen atom of the major isomers:
and E-isomers (Figure 1).
DdH =0.07–0.10 ppm, DdC =0.2 ppm.
Predominant formation of the Z-isomer should be
The predominant formation of the E-isomers of a-
expected for diethyl 1-(p-anisylimino)-2,2-dimethyl- iminophosphonates 2a–f and Z-isomers of a-imino-
propylphosphonate (2g) containing the bulky tert- phosphonates 2g, h has been additionally verified by
butyl substituent. In this case, the diethoxyphosphoryl the analysis of the spin-spin coupling constants. It is
3
group of the major isomer and the tert-butyl group of known[32] that in unsaturated systems the JC,P con-
the minor isomer should be exposed to the shielding stants for a trans-arrangement are higher than for a
effect of the aromatic substituent at the nitrogen cis-arrangement of the interacting nuclei. In fact, the
observed value of the vicinal spin-spin coupling con-
stant between the phosphorus nuclei and the nodal
carbon of the aromatic substituent at the nitrogen
atom in the major isomers of a-iminophosphonates
2a–f is 31.5–33.7 Hz, whereas for the major isomers of
2g, h this value is 13.9–17.6 Hz.
To prove the predominant E-configuration of the
imine bond for a-iminophosphonates 2a–f and the Z-
Scheme 1. Synthesis of a-iminophosphonates 2a–h.
configuration for 2g, h NOE difference experiments
were performed for compounds 2d and g. In the
1H NMR spectrum of 2d, the assignment of the sig-
nals of the aromatic protons is unambiguous due to
1
characteristic H-19F spin-spin coupling constants (see
Supporting Information). Irradiation of the aromatic
protons of the p-anisyl group reveals an NOE en-
hancement of the ortho protons of the 4-fluorophenyl
substituent [hH(2,6)(CHp-anisyl)=1.9%], but no effect on
Figure 1. Z- and E-isomers of a-iminophosphonates 2b–h.
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Nataliya S. Goulioukina et al.
FULL PAPERS
the protons of the diethoxyphosphoryl group. On the
A characteristic feature of the mass spectra of a-
contrary, in the case of a-iminophosphonate 2g the ir- iminophosphonates 2b–h is a considerable intensity of
radiation of the aromatic protons at d=6.70 ppm re- the [MÀP(O)
(OEt)2]+ ion peaks. The fragmentation
veals an NOE enhancement of the methylene and of aliphatic a-iminophosphonates 2g, h is accompa-
AHCTREUNG
a
a
b
À
À
methyl protons of the diethoxyphosphoryl group nied by both C P bond cleavage, and C C bond
[hHarom(CH2)=0.2%, hHarom
(CH3)=0.2%], but no cleavage, thus the [MÀR]+ peaks are observed.
effect on the protons of the tert-butyl group. The reduction of a-iminophosphonates is rather
A
ACHTREUNG
The IR spectra of a-iminophosphonates 2a–h ex- scarcely described in literature. As a rule, the reduc-
hibit a characteristic set of bands corresponding to vi- tion is accomplished by sodium borohydrides NaBH-
brations of the diethoxyphosphoryl fragment.[33] The
A
[34]
stretching vibration of the P=O bonds appears in the of a-ketophosphonic acids was carried out using
region of 1225–1260 cmÀ1. The prominent band at NaBH4
or its tritium analogue NaB3H4.[39] An at-
[38]
1015–1040 cmÀ1 corresponds to n
A
À
An intense band at 1580–1615 cmÀ1 corresponds to 2,2-difluoroethylphosphonate by hydrogen in the
the C=N stretching vibration. For diethyl (p-anisylimi- presence of palladium on carbon was unsuccessful,[35]
no)(2-thienyl)methylphosphonate (2f), two bands are perhaps for steric reasons. The catalytic hydrogena-
observed in this region. They correspond, probably, to tion of g-substituted a-iminopropenylphosphonates
the E- and Z-isomers formed in a ratio of 78/22. In- was published[30] while the present publication was in
tense absorptions at 1135 and 1155 cmÀ1 in the spec- preparation.
trum of a-iminophosphonate 2h correspond to vibra-
tions of the CF3 group.
The conditions for hydrogenation of a-imino-
phosphonates in the presence of palladium on carbon
were optimized on the model substrate 2a, by varying
the solvent (methanol or chloroform), reaction tem-
perature (ambient or reflux), palladium content in the
catalyst (5 or 10 wt%), and the amount of the latter
(S/Pd mol ratio 100/1 or 20/1). The reaction course
was monitored using 31P NMR for the disappearance
of the signals of the initial phosphonate 2a at dP =6.5
and 2.4 ppm and the increase of the signal from dieth-
yl a-(phenylamino)benzylphosphonate (3a) at dP =
22.8 ppm (Scheme 2).
The obtained results (Table 1) show that under
1 bar hydrogen pressure the reduction of a-imino-
phosphonate 2a in boiling methanol in the presence
of 10% Pd/C (S/Pd mol ratio 20/1) occurs smoothly
within 2 h and affords aminophosphonate 3a as a
single reaction product for both microscale (entry 1)
and preparative scale experiments (entry 2).
A decrease of the catalyst amount (S/Pd mol ratio
100/1, entry 3) or the use of other catalyst with a
lower content of metal (5% Pd/C instead of 10% Pd/
C, entry 4) noticeably decreases the rate and selectivi-
Scheme 2. Hydrogenation of 2a catalyzed by palladium on
carbon and possible side reactions.
Table 1. Hydrogenation of 2a catalyzed by palladium on carbon (1 bar H2, c=0.03 mol/L).
Entry
Solvent
Catalyst
S/Pd
Temperature [8C]
Time [h]
Yield [%][a]
3a
2a
HP(O)
A
4
5
1
MeOH
MeOH
MeOH
MeOH
MeOH
CHCl3
10% Pd/C
10% Pd/C
10% Pd/C
5% Pd/C
10% Pd/C
10% Pd/C
20/1
20/1
100/1
20/1
100/1
20/1
65
65
65
65
20
61
2
2
2
1
1
1
100
100[c]
80
84
38
0
0
7
13
11
56
0
0
1
0
1
0
0
0
8
3
22
35
0
0
4
0
28
0
2[b]
3
4
5
6
9
[a]
Determined by 31P NMR.
Preparative experiment (c=0.1 mol/L).
Preparative yield 86%.
[b]
[c]
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Synthesis of Racemic and Optically Active a-aminophosphonates
FULL PAPERS
Scheme 3. Hydrogenation of 2b–d, f–h catalyzed by palladium on carbon.
ty of the process. The decrease of reaction tempera-
For the reduction of a-iminophosphonate 2g con-
ture to ambient (entry 5), or the use of chloroform as taining a bulky tert-butyl substituent, the conversion
solvent (entry 6) results in the predominant formation and the yield of the target product under 1 bar hydro-
of decomposition products – diethyl phosphite (dP = gen pressure remained low with an increase in the
7.6 ppm) and diethyl benzoylphosphonate (4) (dP = catalyst amount (S/Pd mol ratio 10/1) and when meth-
À1.1 ppm), as well as the reduction product of the anol was replaced by higher boiling ethanol. We suc-
latter, diethyl a-hydroxybenzylphosphonate (5) (dP = ceeded to hydrogenate 2g in good yield only by in-
21.6 ppm).
creasing of the hydrogen pressure to 70 bar and pro-
The results of the hydrogenation of a-iminophosph- longing the reaction time to 20 h.
onates 2b–d, f–h are presented in Scheme 3 and
The hydrogenation of a-iminophosphonates 2e, f
Table 2. The reduction of a-iminophosphonates 2b–d, containing heteroaromatic fragments met with diffi-
h in dilute solutions (c=0.03 mol/L) takes place as culties. In the case of the furyl derivative 2e, the reac-
readily as the reduction of 2a: within 2–2.5 h at 100% tion is complicated by the formation of many side
conversion the yields of a-aminophosphonates 3b–d, products, including, probably, products of the hydro-
h are 92–100%. However, under the conditions of the genation of the heteroaromatic ring. We failed to iso-
preparative experiment with an increase in the sub- late and characterize the target product. In the case
strate concentration (c=0.07–0.08 mol/L) the rate of the thienyl derivative 2f, the maximal yield of a-
and selectivity of the process decrease considerably. aminophosphonate 3f estimated by 31P NMR is 70%
a-Aminophosphonates 3b–d, h were synthesized in at 90% conversion. The target product 3f was isolated
quantitative yields when the hydrogenation was car- with a low preparative yield and characterized spec-
ried out under 50 bar at room temperature.
trally.
Table 2. Hydrogenation of a-iminophosphonates 2b–d, f–h catalyzed by palladium on carbon (MeOH, 10% Pd/C, S/Pd mol
ratio 20/1).
Substrate 2
R
Concentration Pressure [bar] Temperature [8C] Time [h] Conversion [%][a] Yield of 3 [%][a]
[mol/L]
AHCTREUNG
2b
Ph
0.03
0.08
0.10
1
1
50
1
1
50
1
1
50
1
70
1
1
1
50
70
70
1
65
65
20
65
65
20
65
65
20
65
20
65
65
78
20
20
20
65
20
2
3
3
2
2.5
3
2.5
2
100
88
100
100
75
100
100
90
100
34
92
72
100
94
50
100
100
86
100
17
2c
4-MeC6H4 0.03
0.07
0.09
2d
4-FC6H4
0.03
0.08
0.09
0.03
0.015
0.03
0.03
0.03
0.02
0.02
0.10
0.03
0.10
3
2f
2g
2-thienyl
2.5
24
2.5
2.5
3
90
32
48
34
70
t-Bu
22
37[b]
21[c]
69
3
70
20
20
2
100
100
100
100
100
100
93
2h
F3C
50
3
91
[a]
Determined by 31P NMR.
S/Pd mol ratio 10/1.
In EtOH.
[b]
[c]
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The purity and structures of the isolated a-amino- 10 h, but the isolated sample of 3a was optically inac-
phosphonates 3a–d, g, h were confirmed by the ele- tive.
mental analysis and spectral data. In the IR spectra of
Iridium complexes with ligands involving a phos-
a-aminophosphonates 3a–d, f–h vibrational bands of phite donor center showed good results in the asym-
the diethoxyphosphoryl fragment are observed, in metric hydrogenation of N-(1-arylethylidene)ani-
particular, the band of n
(P=O) vibrations at 1240– line.[52,53] The chiral amidophosphite MonoPhos[54] was
G
1250 cmÀ1 and the band in the region of 1030– successfully applied in the Ir(I)-catalyzed hydrogena-
1060 cmÀ1 corresponding to vibrations of the O C tion of the model 2,3,3-trimethylindolenine.[55] Having
À
bond. On the contrary, the stretching band of the C= in hand a family of ligands of phosphite (L2–6)[56–58]
N bond at 1580–1615 cmÀ1 disappears, and a broad
band at 3300–3340 cmÀ1, typical for n
tions, is observed.
A
À
Table 3. Ligands L2–8 in the catalytic asymmetric hydroge-
nation of 2bÀ (CH2Cl2, 50 bar H2, 208C, 24 h,
In the 1H NMR spectra of a-aminophosphonates
3a–d, f–h the doublet of the methine proton at 3.3–
5.0 ppm (2JP, H =18.7–24.3 Hz) is a main characteristic
feature. In the 13C NMR spectra, the doublet of the a-
carbon atom of a-aminophosphonates lies at 56.0–
61.2 ppm (1JC,P =147.1–152.2 Hz) (for a-iminophos-
[Ir
(COD)2]+SbF6 as precatalyst, S/Ir/L=100/3/6 for mono-
A
or 100/3/3 for bidentate ligands).
L
Conversion Yield of
of 2b [%][a] 3b* [%][a]
ee [%]
A
nascent a-C* stereocenter the ethoxy groups become
1
diastereotopic and appear in the 13C and H NMR
74
68
62
70
57
66
26
30
19
31
13
14
7
spectra as two sets of signals.
Compared to the asymmetric hydrogenation of C=
C and C=O multiple bonds, the homogeneous stereo-
selective hydrogenation of the C=N bond remains
poorly studied, although considerable progress in this
area has been achieved recently.[40–42] The success is
related, first of all, to the application of chiral Ti, Ru,
Rh, and especially Ir complexes. In the last case, good
results are provided by the use of ligands of the phos-
phino-oxazoline type.[40,41,43–50] The iridium(I) cationic
3
23
38
37
complex ([Ir
N
N
ing chiral ligand L1 of the phosphino-oxazoline type
has been used by us previously[51] in the homogeneous
enantioselective hydrogenation of 1-arylethenyl-
phosphonates, which gave phosphorus analogues of
Naproxen and Ibuprofen with ees of 95 and 88%, re-
spectively. However, our attempts to use the same
complex in the hydrogenation of a-iminophospho-
nates failed. In dichloromethane or chloroform (com-
monly used solvents for this type of catalysts) the hy-
drogenation of a-iminophosphonate 2a does not take
place at all or is too slow in the whole ranges of tem-
perature (20–808C) and pressure (10–110 bar) stud-
ied. When methanol is used as solvent under drastic
conditions (110 bar, 808C), conversion was 95% and
the yield of a-aminophosphonate 3a was 76% after
69
80
46
44
68
16
6
24
[c]
-
12[d]
[a]
[b]
[c]
[d]
Determined by 31P NMR.
Fc=ferrocenyl.
À
[Rh
[Rh
G
Figure 2. Structure of the complex [Ir
U
[BArF]À.
(COD)2]+BF4 as precatalyst.
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Synthesis of Racemic and Optically Active a-aminophosphonates
and amidophosphite (L7, 8)[59,60] types, we tested them
FULL PAPERS
The chiral bisphosphines present the widest group
in the hydrogenation of a-iminophosphonate 2b. The of ligands used in Rh(I)- and Ir(I)-catalyzed stereose-
results obtained are presented in Table 3. Both the lective hydrogenation of the C=N bond.[40,41,61–63] We
monodentate L2, 3 and P,N-bidentate L4–6 BINOL- have also turned our attention to the classical BINAP
derived phosphite ligands revealed a low stereo-dif- ligand (Scheme 4).
ferentiating ability: the optical yield of the product
It was found that the hydrogenation of the model
3b* did not exceed 38% ee. A satisfactory asymmetric substrate 2b at room temperature and hydrogen pres-
induction was revealed by the bidentate P-chiral di- sure of 50 bar in the presence of the cationic rhodium
U
donor center and, especially, the monodentate lution of the [Rh
(COD)2]+SbF6 precatalyst in metha-
À
BINOL-based amidophosphite L8 (analogue of nol to a solution of a stoichiometric amount of (R)-
MonoPhos) (69 and 80% ee, respectively). Unfortu- BINAP in the same solvent resulted in the formation
nately, the hydrogenation rate of a-iminophosphonate of a-aminophosphonate 3b* in quantitative yield after
2b using the ligands L2–8 turned out to be very low, 6 h, with enantiomeric excess reaching 94% ee
as the yield of the target product 3b* was 13–31% (Table 4, entry 1). When the S/Rh mol ratio was
even after a day, and decomposition products, such as changed from 20/1 to 100/3 (entry 2), the optical yield
diethyl benzoylphosphonate (4) and diethyl phos- stays roughly constant within the measurement error,
phite, were formed in considerable amounts. Our at- but decreases substantially at S/Rh=100/1 (entry 3).
tempts to optimize the reaction conditions by using The yield of by-products simultaneously increases no-
the ligand L8 (variation of the hydrogen pressure ticeably. The reaction rate as well as chemo- and steÀ-
from 10 to 100 bar and temperature in the 20–808C reoselectivity decrease significantly when the SbF6
interval) were unsuccessful, as the increase in the counterion is replaced by BF4À (entry 4).
yield of a-aminophosphonate 3b* was inevitably ac-
The variation of pressure from 10 to 70 bar (at
companied by a substantial decrease in the stereose- 208C) exerts no substantial effect on the stereoselec-
lectivity of the process. The replaÀcement of the iridi- tivity of the process when S/Rh=20/1 (entries 1, 5–7)
um precatalyst [Ir
ones [Rh
no positive effect as well.
U
N
(COD)2]+BF4 gave trace amounts of by-products were formed under hy-
drogen pressures below 70 bar (entries 2, 9). Under
10 bar pressure, the target product 3b* is formed in a
quantitative yield at 60–808C, the optical yield being
94–92% ee (entries 10, 11).
It turned out that the order of reagent mixing
during the catalyst preparation is of principal signifi-
cance. The catalyst sample prepared by the inverse
order of mixing, i.e., by a slow addition of a methanol
Scheme 4. Rh-catalyzed asymmetric hydrogenation of
2b–d, f.
solution of (R)-BINAP to
a
solution of
À
Table 4. Rh-catalyzed asymmetric hydrogenation of 2b {MeOH, [Rh
A
Entry
S/Rh[a]
Pressure [bar] Temperature [8C]
Time [h] Conversion of 2b [%][b] Yield of 3b* [%][b]
ee [%]
1
2
3
4
5
6
7
8
20/1
50
50
50
20
20
20
20
20
20
20
20
20
60
80
20
6
6
6
6
24
24
24
6
6
6
100
100
100
88
100
100
100
100
93
100
98
92
94
91
79
51
91
91
92
91
90
94
92
65
100/3
100/1
100/1[c] 50
79
20/1
20/1
20/1
100/3
100/3
100/3
100/3
20/1[d]
70
20
10
70
10
10
10
50
100
100
100
100
90
100
100
92
9
10
11
12
100
100
100
6
24
[a]
À
Unless otherwise stated, the catalyst was prepared by addition of the solution of [Rh
BINAP.
G
[b]
[c]
[d]
Determined by 31P NMR.
À
[Rh
A
The catalyst was prepared by addition of the solution of (R)-BINAP to [Rh
(COD)2]+SbF6 precatalyst.
U
Adv. Synth. Catal. 2008, 350, 482 – 492
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asc.wiley-vch.de
487

Nataliya S. Goulioukina et al.
FULL PAPERS
À
[Rh
A
ing ability of 65% ee (entry 12). The replacement of conversion of 23% (70 bar H2, 608C, 6 h, S/Rh=100/
methanol by CH2Cl2 increases the enantiomeric 3). No result was obtained by the variation of the
excess to 73% ee; however, the yield of the target pressure and temperature, an increase in the catalyst
product 3b* decreases to 34%, and the decomposition amount, and prolongation of the reaction time. The
products 4 (37%) and HP(O)(OEt)2 (10%) are accu- hydrogenation of trifluoromethyl a-iminophospho-
U
mulated in significant amounts, which agrees well nate 2h is non-selective and most probably complicat-
with published data (see, e.g.[64]) on the participation ed by C F bond cleavage; the structure of the by-
À
of the MeOH molecule in the catalytic cycle. The iri- product deserves further clarification.
dium precatalyst [Ir
ty.
A
Under the optimal conditions found (MeOH, Conclusions
10 bar H2, 608C, S/Rh=100/3), we tested the hydro-
genation of a series of a-iminophosphonates 2c, d, f–h In summary, we have shown that the palladium-cata-
(Table 5). The reduction of Me-subsituted a-imino- lyzed hydrogenation of diethyl a-iminomethyl phos-
phosphonate 2c gave a-aminophosphonate 3c* in phonates bearing aryl, heteroaryl, tert-butyl or tri-
quantitative yield and 94% ee after 6 h. The hydroge- fluoromethyl substituents in the a-position can serve
nation rate of a-iminophosphonates 2d, f containing as a convenient synthetic approach to a-amino-
more p-donor aromatic substituents at the a-C atom phosphonates of practical interest. Asymmetric hy-
decreases noticeably, which is consistent with the drogenation of the a-iminophosphonates with a pre-
mechanism proposed earlier,[63,65] including the hy- dominant E-configuration of the imine bond using the
À
dride transfer from Rh to the a-C atom of h2-(C=N)- [Rh
A
À
coordinated imine with formation of the Rh N bond. strated to provide a new general method for the syn-
The completion of the reaction in the case of fluo- thesis of optically active a-aminophosphonates con-
rine-substituted a-iminophosphonate 2d requires 10 h, taining the quaternary b-carbon atom with enantio-
the enantiomeric excess being 75%. The conversion meric excesses up to 94%.
of thienyl a-iminophosphonate 2f comes to 88% after
12 h and remains virtually unchanged with the prolon-
gation of the reaction time, which is due, probably, to
the inhibition of the catalyst during the reaction
Experimental Section
Chloroform and dichloromethane were distilled over P2O5,
stored in the dark under argon and distilled over CaH2 prior
to use. Methanol was dried over magnesium methoxide fol-
lowed by distillation. Palladium on carbon (10% Pd) (Al-
drich) and (R)-BINAP (97%, Aldrich) were used without
course. Approximately the same conversion is ach-
ieved with S/Rh=20/1; the yield of the target product
3f* increases to 82% with 43% ee.
Attempts at the homogeneous hydrogenation of a-
iminophosphonates 2g, h with predominant Z-config-
uration have not been successful. For the sterically
hindered tert-butyl a-iminophosphonate 2g the maxi-
À
À
purification. The [Rh
C
G
À
and [Ir
A
ported methods.[66] The [Ir
(COD)L1]+
ACHTREUNG
À
Table 5. Rh-catalyzed asymmetric hydrogenation of 2b–d, f–h {MeOH, 608C, [Rh
ACHTREUNG
BINAP=100/3/3}.
Substrate 2
R
Pressure [bar]
Time [h]
Conversion of 2 [%][a]
Yield of 3* [%][a]
ee [%]
2b
2c
2d
Ph
4-MeC6H4
4-FC6H4
10
10
10
10
10
10
10
70
75
10
100
6
6
8
10
12
12
6
8
13
6
100
100
90
100
88
84
11
23
35
100
100
84
94
94
94
75
43
2f
2g
2-thienyl
69
82[b]
8
t-Bu
17
13[c,d]
21
2h
F3C
40
85
6
47[c]
Determined by 31P NMR.
S/Rh/(R)-BINAP=20/1/1.
At 808C.
[a]
[b]
[c]
[d]
S/Rh/(R)-BINAP=100/6/6.
488
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ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2008, 350, 482 – 492

Synthesis of Racemic and Optically Active a-aminophosphonates
FULL PAPERS
synthesized in the research group of Prof. A. Pfaltz and
kindly presented to the authors. Triethyl phosphite was
treated with Na, then distilled under reduced pressure.
Amides were prepared by the standard Schotten–Baumann
procedure. N-Phenylbenzenecarboxyimidoyl chloride (1a)
was synthesized as published.[67] The melting points of prod-
ucts were measured with Electrothermal 9100 indicator in a
sealed capillary.
Diethyl
a-(p-anisylimino)-4-fluorobenzylphosphonate
(2d): Synthesized similarly to 2a by stirring a mixture of
3.951 g (14.98 mmol) of 1d and 3.6 mL (20.99 mmol) of
triethyl phosphite at 120–1508C for 3 h and obtained as a
yellow oil; yield: 98%; bp 171–1828C (10À1 Torr).
Diethyl (p-anisylimino)(2-furyl)methylphosphonate (2e):
A
Synthesized similarly to 2a by stirring a mixture of 2.368 g
(10.05 mmol) of 1e and 2.0 mL (11.66 mmol) of triethyl
phosphite at 120–1308C for 3 h and obtained as a purple oil;
yield: 36%; bp 1808C (10À1 Torr).
N-(p-Anisyl)benzenecarboxyimidoyl chloride (1b): Syn-
thesized by a procedure similar to[67] by stirring of a mixture
of N-(p-anisyl)benzamide (3.964 g, 17.44 mmol) with thionyl
chloride (2.5 mL, 34.27 mmol) at 808C for 2.5 h. Excess
SOCl2 was removed under reduced pressure, and the residue
was distilled under vacuum affording 1b as pale yellow crys-
tals; yield: 3.641 g (85%); bp 174–1768C (2 Torr).
Diethyl
(p-anisylimino)(2-thienyl)methylphosphonate
(2f): Synthesized similarly to 2a by stirring a mixture of
2.483 g (9.86 mmol) of 1f and 1.7 mL (9.91 mmol) of triethyl
phosphite at 1608C for 2 h and obtained as an orange oil;
yield: 56%; bp 185–1908C (10À1 Torr).
Diethyl 1-(p-anisylimino)-2,2-dimethylpropylphosphonate
(2g): Synthesized similarly to 2a by stirring a mixture of
5.000 g (22.15 mmol) of 1g and 3.8 mL (22.16 mmol) of
triethyl phosphite at 1708C for 2 h and obtained as a yellow
oil; yield: 80%; bp 150–1568C (10À1 Torr).
Diethyl 1-(p-anisylimino)-2,2,2-trifluoroethylphosphonate
(2h): Synthesized similarly to 2a by stirring a mixture of
0.717 g (3.02 mmol) of 1h and 0.5 mL (2.92 mmol) of triethyl
phosphite at 120–1358C for 2 h and obtained as a yellow oil;
yield: 59%; bp 145–1558C (10À1 Torr).
N-(p-Anisyl)-4-methylbenzenecarboxyimidoyl
(1c): Synthesized similarly to 1b from 3.457 g (14.33 mmol)
of N-(p-anisyl)-4-methylbenzamide and 4.0 mL
(54.84 mmol) of SOCl2 as pale yellow crystals; yield: 87%;
bp 180–1888C (2 Torr).
chloride
N-(p-Anisyl)-4-fluorobenzenecarboxyimidoyl
chloride
(1d): Synthesized similarly to 1b from 4.100 g (16.72 mmol)
of N-(p-anisyl)-4-fluorobenzamide and 6.5 mL (89.11 mmol)
of SOCl2 as pale yellow crystals; yield: 91%; bp 160–1648C
(2 Torr).
N-(p-Anisyl)furan-2-carboxyimidoyl chloride (1e): Syn-
thesized similarly to 1b from 5.000 g (23.02 mmol) of N-(p-
anisyl)-2-furamide and 5.1 mL (69.92 mmol) of SOCl2 as
pale yellow crystals; yield: 78%; bp 1528C (2 Torr).
Diethyl a-(Phenylamino)benzylphosphonate (3a)
a-Iminophosphonate 2a (0.500 g, 1.58 mmol) in dry metha-
nol (50 mL) was placed in a flask equipped with a magnetic
stirrer, reflux condenser with a three-way adapter, gas bub-
bler, and long gas inlet tube passing through the condenser
to the bottom of the flask. The device was filled with dry
argon, and 0.083 g of 10% Pd/C (S/Pd=20/1) was added.
The argon supply was stopped, and hydrogen was passed
through the device using the same inlet tube. The reaction
mixture was refluxed with stirring for 2 h in a weak hydro-
gen current and then cooled. The catalyst was filtered off
using a short pad of silica gel. The mother liquor was evapo-
rated to dryness under vacuum to furnish spectrally pure a-
aminophosphonate 3a as colorless crystals, turning dark in
the air; yield: 0.431 g (86%). After recrystallization from al-
cohol the yield of 3a was 0.300 g (60%), mp 89–908C.[69–72]
N-(p-Anisyl)thiophene-2-carboxyimidoyl chloride (1f):
Synthesized similarly to 1b from 2.500 g (10.72 mmol) of N-
(p-anisyl)thiophene-2-carboxamide
and
4.0 mL
(54.84 mmol) of SOCl2 as a pale yellow oil; yield: 92%; bp
180–1858C (2 Torr).
N-(p-Anisyl)-2,2-dimethylpropanimidoyl chloride (1g):
Synthesized similarly to 1b from 6.000 g (28.95 mmol) of N-
(p-anisyl)-2,2-dimethylpropanamide
and
2.6 mL
(35.65 mmol) of SOCl2 as pale yellow crystals; yield: 87%;
bp 1088C (2 Torr).
N-(p-Anisyl)-2,2,2-trifluoroethanimidoyl chloride (1h):
Synthesized by the method described in the literature.[68]
Pale yellow viscous liquid; bp 1268C (12 Torr).[37,68]
Diethyl a-(Phenylimino)benzylphosphonate (2a)
Diethyl a-(p-Anisylamino)benzylphosphonate (3b)
A Claisen flask equipped with a magnetic stirrer and filled
with dry argon was loaded with 1a (6.289 g, 29.16 mmol) and
triethyl phosphite (5.0 mL, 29.16 mmol). The reaction mix-
ture was stirred at 1608C for 2 h and then distilled under
vacuum in an argon flow affording 2a as a yellow oil; yield:
6.542 g (71%); bp 175–1808C (10À1 Torr).[31]
Diethyl a-(p-anisylimino)benzylphosphonate (2b): Syn-
thesized similarly to 2a by stirring a mixture of 3.641 g
(14.82 mmol) of 1b and 3.0 mL (17.15 mmol) of triethyl
phosphite at 140–1508C for 3 h and obtained as a yellow oil;
yield: 79%; bp 204–2108C (10À1 Torr).
Compound 2b (1.000 g, 2.88 mmol) in dry methanol (30 mL)
and 10% Pd/C (0.153 g, S/Pd=20/1) were placed in a steel
autoclave with a glass inset equipped with a magnetic stirrer
and filled with dry argon. The autoclave was sealed and
pressurized with H2 (50 bar), and the reaction mixture was
stirred at room temperature for 3 h. The catalyst was filtered
off using a celite pad, the mother liquor was evaporated to
dryness under vacuum to furnish spectrally pure a-amino-
phosphonate 3b as a yellow oil; yield: 0.989 g (98%). Color-
less crystals, turning dark in air, were obtained in 83% yield
after crystallization from petroleum ether, mp 70–738C.
Diethyl
a-(p-anisylimino)-4-methylbenzylphosphonate
Diethyl
a-(p-anisylamino)-4-methylbenzylphosphonate
(2c): Synthesized similarly to 2a by stirring a mixture of
3.222 g (12.40 mmol) of 1c and 4.1 mL (23.91 mmol) of
triethyl phosphite at 140–1658C for 2.5 h and obtained as a
dark yellow oil; yield: 79%; bp 185–1908C (10À1 Torr).
(3c): Synthesized similarly to 3b as a yellow oil by the hy-
drogenation of 2c (0.500 g, 1.38 mmol) in dry methanol
(15 mL) in the presence of 10% Pd/C (0.073 g, S/Pd=20/1);
yield: 95%. Colorless crystals, turning dark in air, were ob-
Adv. Synth. Catal. 2008, 350, 482 – 492
ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
489

Nataliya S. Goulioukina et al.
FULL PAPERS
tained in 81% yield after crystallization from petroleum
ether, mp 69–738C.
Acknowledgements
Diethyl
a-(p-anisylamino)-4-fluorobenzylphosphonate
We are grateful to Prof. A. Pfaltz (University of Basel, Swit-
zerland) for a sample of [Ir
(COD)L1]+[BArF]À complex and
Dr. D. P. Krut’ko (Moscow State University, Russia) for assis-
tance with NOE difference experiments. Financial support of
this work by INTAS grant N 05–1000008–8064 and RFBR
grants N 04–03–39017 and N 05–03–33013 is gratefully ac-
knowledged.
(3d): Synthesized similarly to 3b as a yellow oil by the hy-
drogenation of 2d (1.000 g, 2.74 mmol) in dry methanol
(30 mL) in the presence of 10% Pd/C (0.145 g, S/Pd=20/1);
yield: 99%. Colorless crystals, turning dark in air, were ob-
tained in 71% yield after crystallization from petroleum
ether, mp 45–488C.
G
ACHTREUNG
Diethyl
(p-anisylamino)(2-thienyl)methylphosphonate
(3f): Synthesized similarly to 3b by the hydrogenation of 2f
(0.055 g, 0.15 mmol) in dry methanol (10 mL) in the pres-
ence of 10% Pd/C (0.008 g, S/Pd=20/1). Hydrogen pressure
70 bar, reaction time 24 h.
Diethyl (p-anisylamino)-2,2-dimethylpropylphosphonate
(3g): Synthesized similarly to 3b as a yellow oil by the hy-
drogenation of 2g (1.000 g, 3.05 mmol) in dry methanol
(30 mL) in the presence of 10% Pd/C (0.162 g, S/Pd=20/1).
Hydrogen pressure 70 bar, reaction time 20 h; yield: 100%.
Beige crystals of 3g were obtained in 54% yield after crys-
tallization from petroleum ether, mp 59–618C.
Diethyl 1-(p-anisylamino)-2,2,2-trifluoroethylphosphonate
(3h): Synthesized similarly to 3b as a yellow oil by the hy-
drogenation of 2h (0.520 g, 1.53 mmol) in dry methanol
(16 mL) in the presence of 10% Pd/C (0.082 g, S/Pd=20/1);
yield: 98%. Colorless crystals, turning dark in air, were ob-
tained in 48% yield after crystallization from petroleum
ether, mp 57–608C.[37]
References
[1] V. P. Kukhar, H. R. Hudson, (Eds.), Aminophosphonic
and Aminophosphinic Acids: Chemistry and Biological
Activity, Wiley, Chichester, 2000, 660 p .
[2] V. P. Kukhar, V. A. Solodenko, Russ. Chem. Rev. (Engl.
Trans.)1987, 56, 859–874.
[3] J. Uziel, J. P. Genet, Russ. J. Org. Chem. (Engl. Trans.)
1997, 33, 1521–1543.
[4] R. A. Cherkasov, V. I. Galkin, Russ. Chem. Rev. (Engl.
Trans.) 1998, 67, 857–882.
[5] H. Grçger, B. Hammer, Chem. Eur. J. 2000, 6, 943–
948.
[6] J.-A. Ma, Chem. Soc. Rev. 2006, 35, 630–636.
[7] U. Schollkopf, I. Hoppe, A. Thiele, Liebigs Ann. Chem.
1985, 555–559.
[8] J. J. Talley, (Monsanto Company), US Patent 5,321,153,
1994; Chem. Abstr. 1994, 121, 301315r.
[9] M. J. Burk, T. A. Stammers, J. A. Straub, Org. Lett.
1999, 1, 387–390.
Asymmetric Hydrogenation of 2b (Typical Example)
The Schlenk flask was dried at 1508C for 40 min, filled with
dry argon, and loaded with (R)-BINAP (2.7 mg, 4.34 mmol)
dissolved in 4 mL Àof deaerated dry methanol. A solution of
[10] M. Kitamura, M. Yoshimura, M. Tsukamoto, R.
Noyori, Enantiomer 1996, 1, 281–303.
[Rh
(COD)2]+SbF6 (2.6 mg, 4.68 mmol) in MeOH (4 mL)
G
[11] Grassert, U. Schmidt, S. Ziegler, C. Fischer, G. Oehme,
Tetrahedron: Asymmetry 1998, 9, 4193–4202.
[12] U. Schmidt, H. W. Krause, G. Oehme, I. Grassert, M.
Michalik, C. Fischer, Chirality 1998, 10, 564–572.
[13] J. Holz, R. Sturmer, U. Schmidt, H.-J. Drexler, D.
Heller, H.-P. Krimmer, A. Borner, Eur. J. Org. Chem.
2001, 4615–4624.
[14] I. D. Gridnev, M. Yasutake, T. Imamoto, I. P. Belet-
skaya, Proc. Natl. Acad. Sci. USA 2004, 101, 5385–
5390.
[15] L. N. Markovskii, Yu. G. Shermolovich, G. G. Bara-
shenkov, V. P. Kukhar, V. A. Soloshonok, A. B. Roz-
henko, Zhur. Obsh. Khim. (Russian) 1990, 60, 2244–
2247.
[16] L. Maier, P. J. Diel, Phosphorus, Sulfur and Silicon
1991, 57, 57–64.
was added dropwise with vigorous stirring for 30 min. After
10 min, a-iminophosphonate 2b (50.0 mg, 0.14 mmol) was
introduced in an argon flow. The resultant homogeneous,
weakly yellow solution was stirred for 10 min more and
transferred by a syringe into a steel autoclave washed with
MeOH and filled with argon. The Schlenk flask was washed
with MeOH (2 mL), which was added to the main solution.
The autoclave was sealed, pressurized with H2 to 10 bar, the
temperature was increased to 608C, and the reaction mix-
ture was stirred for 6 h. After the end of the experiment, the
solution was evaporated under reduced pressure. The resi-
due was dissolved in CDCl3 and analyzed by 31P and
1H NMR. The enantiomeric excess was determined by
HPLC on a Bischoff liquid chromatograph [chiral column
(R,R)-WHELK-01, hexane/i-PrOH, 9/1, 1.0 mLminÀ1,
254 nm]. The retention times of the enantiomers of 3b*
were 12.1 and 13.1 min (ratio 1/31).
[17] J. Zon, N. Amrhein, R. Gancarz, Phytochemistry 2002,
59, 9–21.
[18] S. A. Beers, C. F. Schwender, D. A. Loughney, E.
Malloy, K. Demarest, J. Jordan, Bioorg. Med. Chem.
1996, 4, 1693–1701.
[19] D. Green, G. Patel, S. Elgendy, J. A. Baban, G. Clae-
son, V. V. Kakkar, J. Deadman, Tetrahedron 1994, 50,
5099–5108.
Experiments on the optimization of reaction conditions of
enantioselective hydrogenation of a-iminophosphonate 2b
and hydrogenation of other a-iminophosphonates 2 were
carried out similarly. The retention times of the two enantio-
mers were: 3c*, 12.5 and 14.0 min (ratio 1/31); 3d*, 12.1 and
13.5 min (ratio 1/7), 3f*, 7.4 and 8.3 min (ratio 1/2.5).
[20] Yu. P. Belov, A. Y. Aksinenko, B. Blessington, A. H.
Newman, Chirality 1996, 8, 122–125.
Supporting Information
[21] D. Pettersen, M. Marcolini, L. Bernardi, F. Fini, R. P.
Herrera, V. Sgarzani, A. Ricci, J. Org. Chem. 2006, 71,
6269–6272.
Spectral and analytical data of compounds 1b, e, h, 2 and
3a–d, f–h are given in the Supporting Information.
490
asc.wiley-vch.de
ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2008, 350, 482 – 492

Synthesis of Racemic and Optically Active a-aminophosphonates
FULL PAPERS
[22] G. D. Joly, E. N. Jacobsen, J. Am. Chem. Soc. 2004, 126,
4102–4103.
[47] S.-M. Lu, X.-W. Han, Y.-G. Zhou, Adv. Synth. Catal.
2004, 346, 909–912.
[23] T. Akiyama, H. Morita, J. Itoh, K. Fuchibe, Org. Lett.
2005, 7, 2583–2585.
[24] H. Sasai, S. Arai, Y. Tahara, M. Shibasaki, J. Org.
[48] M. B. Ezhova, B. O. Patrick, B. R. James, F. J. Waller,
M. E. Ford, J. Mol. Catal. A 2004, 224, 71–79.
[49] A. Trifonova, J. S. Diesen, C. J. Chapman, P. G. Ander-
sson, Org. Lett. 2004, 6, 3826–3827.
Chem. 1995, 60, 6656–6657.
[25] B. Saito, H. Egami, T. Katsuki, J. Am. Chem. Soc. 2007,
129, 1978–1986.
[26] P. P. Onysꢀko, T. V. Kim, E. I. Kiseleva, A. D. Sinitsa,
M. Yu. Kornilov, Zhur. Obsh. Khim. (Russian) 1990,
60, 1304–1307.
[27] P. P. Onysꢀko, T. V. Kim, E. I. Kiseleva, A. D. Sinitsa,
Zhur. Obsh. Khim. (Russian) 1996, 66, 936–941.
[28] E. Haak, I. Bytschkov, S. Doye, Eur. J. Org. Chem.
2002, 457–463.
[29] T. Akiyama, M. Sanada, K. Fuchibe, Synlett 2003,
1463–1464.
[30] F. Palacios, J. Vicario, A. Maliszewska, D. Aparicio, J.
Org. Chem. 2007, 72, 2682–2685.
[31] K. Zieloff, H. Paul, G. Hilgetag, Chem. Ber. 1966, 99,
357–361.
[32] B. I. Ionin, B. A. Ershov, A. I. Koltsov, NMR Spectros-
copy in Organic Chemistry, (in Russian), Khimia, Len-
ingrad, 1983, 269 p .
[33] D. Lin-Vien, N. B. Colthup, W. G. Fateley, J. G. Grassel-
li, The Handbook ofInfrared and Raman Characteristic
Frequencies ofOrganic Molecules , Academic Press,
Boston, 1991, 503 p .
[50] C. Blanc, F. Agbossou-Niedercorn, G. Nowogrocki, Tet-
rahedron: Asymmetry 2004, 15, 2159–2163.
[51] N. S. Goulioukina, T. M. Dolgina, G. N. Bondarenko,
I. P. Beletskaya, M. M. Ilyin, V. A. Davankov, A. Pfaltz,
Tetrahedron: Asymmetry 2003, 14, 1397–1401.
[52] S. Vargas, M. Rubio, A. Suarez, A. Pizzano, Tetrahe-
dron Lett. 2005, 46, 2049–2052.
[53] S. Vargas, M. Rubio, A. Suarez, D. del Rio, E. Alvarez,
A. Pizzano, Organometallics 2006, 25, 961–973.
[54] M. van den Berg, A. J. Minnaard, J. G. de Vries, B. L.
Feringa, (DSM N.V.), World Patent WO 02/04466,
2002.
[55] J. W. Faller, S. C. Milheiro, J. Parr, J. Organomet.
Chem. 2006, 691, 4945–4955.
[56] K. N. Gavrilov, S. E. Lyubimov, S. V. Zheglov, E. B.
Benetsky, P. V. Petrovskii, E. A. Rastorguev, T. B.
Grishina, V. A. Davankov, Adv. Synth. Catal. 2007, 349,
1085–1094.
[57] A. A. Kabro, S. E. Lyubimov, M. G. Maksimova, S. K.
Moiseev, K. N. Gavrilov, V. N. Kalinin, Russ. Chem.
Bull. (Engl. Trans.) 2007, 56, 540–542.
[58] K. N. Gavrilov, O. G. Bondarev, R. V. Lebedev, A. I.
Polosukhin, A. A. Shyryaev, S. E. Lyubimov, P. V. Pet-
rovskii, S. K. Moiseev, V. N. Kalinin, N. S. Ikonnikov,
V. A. Davankov, A. V. Korostylev, J. Organomet.
Chem. 2002, 655, 204–217.
[59] V. N. Tsarev, S. E. Lyubimov, O. G. Bondarev, A. A.
Korlyukhov, M. Yu. Antipin, P. V. Petrovskii, V. A. Da-
vankov, A. A. Shiryaev, E. B. Benetsky, P. A. Vologzha-
nin, K. N. Gavrilov, Eur. J. Org. Chem. 2005, 2097–
2105.
[34] A. Ryglowski, P. Kafarski, Tetrahedron 1996, 52,
10685–10692.
[35] G. A. Flynn, D. W. Beight, E. H. W. Bohme, B. W. Met-
calf, Tetrahedron Lett. 1985, 26, 285–288.
[36] W. Huang, Y. Zhang, C. Yuan, Phosphorus, Sulfur and
Silicon 1995, 107, 21–26.
[37] C. Yuan, Y. Zhang, W. Luo, Z. Yao, Heteroat. Chem.
1998, 9, 139–146.
[38] R. M. Khomutov, T. I. Osipova, Yu. N. Zhukov, I. A.
Gandurina, Izv. Akad. Nauk SSSR, Ser. Khim. (Rus-
sian) 1979, 2118–2122.
[60] K. N. Gavrilov, S. E. Lyubimov, S. V. Zheglov, E. B.
Benetsky, V. A. Davankov, J. Mol. Cat. A: Chemical
2005, 231, 255–260.
[61] G. Shang, Q. Yang, X. Zhang, Angew. Chem. 2006, 118,
6508–6510; Angew. Chem. Int. Ed. 2006, 45, 6360–
6362.
[39] R. M. Khomutov, T. I. Osipova, Izv. Akad. Nauk SSSR,
Ser. Khim. (Russian) 1979, 1110–1112.
[40] S. Kobayashi, H. Ishitani, Chem. Rev. 1999, 99, 1069–
1094.
[41] W. Tang, X. Zhang, Chem. Rev. 2003, 103, 3029–3069.
[42] For some recent papers on the application of other re-
ducing reagents in organocatalyzed or organopromoted
reduction of the C=N bond, see: a) O. Onomura, Y.
Kouchi, F. Iwasaki, Y. Matsumura, Tetrahedron Lett.
2006, 47, 3751–3754; b) A. V. Malkov, S. Stoncius,
K. N. MacDougall, A. Mariani, G. D. McGeoch, P. Ko-
covsky, Tetrahedron 2006, 62, 264–284; c) R. I. Storer,
D. E. Carrera, Y. Ni, D. W. C. MacMillan, J. Am.
Chem. Soc. 2006, 128, 84–86; d) G. Li, Y. Liang, J. C.
Antilla, J. Am. Chem. Soc. 2007, 129, 5830–5831.
[43] G. Helmchen, A. Pfaltz, Acc. Chem. Res. 2000, 33,
336–345.
[62] W. R. Cullen, M. D. Fryzuk, B. R. James, J. P. Kutney,
G.-J. Kang, G. Herb, I. S. Thorburn, R. Spogliarich, J.
Mol. Cat. 1990, 62, 243–253.
[63] A. G. Becalski, W. R. Cullen, M. D. Fryzuk, B. R.
James, G.-J. Kang, S. J. Rettig, Inorg. Chem. 1991, 30,
5002–5008.
[64] P. Marcazzan, B. O. Patrick, B. R. James, Organometal-
lics 2005, 24, 1445–1451.
[65] C. J. Longley, T. J. Goodwin, G. Wilkinson, Polyhedron
1986, 5, 1625–1628.
[66] T. V. RajanBabu, T. A. Ayers, G. A. Halliday, K. K.
You, J. C. Calabrese, J. Org. Chem. 1997, 62, 6012–
6028.
[67] J. Braun, W. Pinkernelle, Ber. dtsch. chem. Ges. 1934,
67, 1218–1220.
[44] M. Solinas, A. Pfaltz, P. G. Cozzi, W. Leitner, J. Am.
Chem. Soc. 2004, 126, 16142–16147.
[45] S. Kainz, A. Brinkmann, W. Leitner, A. Pfaltz, J. Am.
Chem. Soc. 1999, 121, 6421–6429.
[68] K. Tamura, H. Mizukami, K. Maeda, H. Watanabe, K.
Uneyama, J. Org. Chem. 1993, 58, 32–35.
[46] S.-F. Zhu, J.-B. Xie, Y.-Z. Zhang, S. Li, Q.-L. Zhou, J.
Am. Chem. Soc. 2006, 128, 12886–12891.
Adv. Synth. Catal. 2008, 350, 482 – 492
ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
491

Nataliya S. Goulioukina et al.
FULL PAPERS
[69] M. M. Kabachnik, T. N. Ternovskaya, E. Z. Zobnina,
I. P. Beletskaya, Russ. J. Org. Chem. (Engl. Trans.)
2002, 38, 484–487.
[71] R. F. Hudson, R. J. G. Searle, F. H. Devitt, J. Chem.
Soc. (B) 1966, 789–792.
[72] M. M. Sidky, F. M. Soliman, R. Shabana, Tetrahedron
[70] E. K. Fields, J. Am. Chem. Soc. 1952, 74, 1528–1531.
1971, 27, 3431–3436.
492
asc.wiley-vch.de
ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2008, 350, 482 – 492