An efficient method for the synthesis of enantiopure phosphine-imidazoline ligands: Application to the Ir-catalyzed hydrogenation of imines

Article abstract of DOI:10.1016/j.tetasy.2004.09.013

Phosphine-imidazoline ligands 8, and the derivatives 16 and 17, which have electron-withdrawing or electron-donating groups in the aminic nitrogen, were synthesized from 2-aryl-imidazolines, which have previously been obtained from dithioesters. The coord

Full text of DOI:10.1016/j.tetasy.2004.09.013

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 3365–3373
An efficient method for the synthesis of enantiopure
phosphine–imidazoline ligands: application to the
Ir-catalyzed hydrogenation of imines
a
Ester Guiu, Carmen Claver, Jordi Benet-Buchholz and Sergio Castill o´ n
b,
c
a,
*
*
a
Departament de Qu ı´ mica Anal ı´ tica i Qu ı´ mica Org a` nica, Universitat Rovira i Virgili, Pl. Imperial T a` rraco 1, 43005 Tarragona, Spain
b
Departament de Qu ´ı mica F ı´ sica i Inorg a` nica, Universitat Rovira i Virgili, Pl. Imperial T a` rraco 1, 43005 Tarragona, Spain
c
Bayer Industry Services, Analytics X-ray Laboratory, Bayer AG, Geb. Q18, Raum 490, D-51368 Leverkusen, Germany
Received 7 June 2004; revised 9 September 2004; accepted 9 September 2004
Abstract—Phosphine–imidazoline ligands 8, and the derivatives 16 and 17, which have electron-withdrawing or electron-donating
groups in the aminic nitrogen, were synthesized from 2-aryl-imidazolines, which have previously been obtained from dithioesters.
4
The coordination of ligand 8 to Ir(I) was studied and the molecular structure of the [Ir(g -COD)8]BF
determined through X-ray diffraction. The in situ prepared Ir(I)/phosphine–imidazoline catalysts were tested in the asymmetric
4
(COD = 1,5-cyclooctadiene)
hydrogenation of ketimines in order to evaluate the influence of the electronic parameters of the ligand on the catalytic reaction.
ꢀ
2004 Elsevier Ltd. All rights reserved.
3
1
. Introduction
ligands 1 were used. Ligands 3 were used in the
4
palladium-catalyzed copolymerization of CO/styrene,
and ligands 4 in the ruthenium-catalyzed Diels–Alder
reaction, and in the diethylzinc addition to aldehy-
6
des, and ligands 2 were used in the Heck reaction.
Chiral metal complexes containing oxazoline derivative
1
5
ligands are efficient catalysts in asymmetric reactions.
Although ligands carrying an imidazoline unit are struc-
turally very similar to oxazoline ligands, they have not
7
2
received as much attention. Ligands 2 (Fig. 1) are some
The imidazoline ring has been synthesized with a variety
8
examples of the chiral imidazoline ligands that have
been used in catalysis, specifically in the iridium-cata-
lyzed reduction of unfunctionalized alkenes. In several
cases, eeÕs were higher than when phosphine–oxazoline
of methods. More specifically, imidazoline derivatives
bearing a 2-substituted aromatic group have been pre-
pared by condensation of a diamine with aryl imidoest-
7
,9,10
ers (Scheme 1a). However, this procedure usually
4
provides only moderate yields.
,5,11
Casey and co-work-
ers have published an improved method that allows imid-
azoline derivatives to be obtained from enantiopure
R2
Ar
X
R1
R
N
Ph
Ph
R
N
N
N
R3
H
PAr2
N
N
HO
R1
R2
R1
H
2
N
N
N
+
(a)
R
R2
H
2
N
R
OMe
N
1
2
X=O
X=NH
3
4
Figure 1.
H
N
R1
R2
R1
R2
R1
R2
3
HO
H N
1. R COX
Cl
N
1. R-NH2
2. NaOH
Cl
R
(b)
2
. SOCl
2
R3
*
Corresponding authors. Tel.: +34 977 559574/56; fax: +34 977
59563; e-mail addresses: claver@quimica.urv.es; castillon@
quimica.urv.es
N
2
5
Scheme 1.
0
957-4166/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.09.013

3366
E. Guiu et al. / Tetrahedron: Asymmetry 15 (2004) 3365–3373
aminoalcohols. The process involves the conversion of
aminoalcohols into N-chloroethylimidoyl chlorides,
which are further reacted with amines and treated in
basic medium to afford the enantiopure imidazolines
O
X
S
X
Cl 1) CH
3
SNa, CH
2
Cl
2
SCH3
2) Lawesson reagent
Toluene reflux
6
,12
(
Scheme 1b).
5
5
a X=Br
b X=F
6a X=Br 91%
6b X=F 94%
Developing efficient catalysts for the enantioselective
conversion of prochiral imines to the corresponding chi-
1
3
Ph
Ph
ral amines is a major research target. Although the
enantioselective hydrogenation of alkenes and ketones
has been successful with several catalytic systems using
phosphorus ligands, the hydrogenation of imines re-
quires further investigation, with high enantioselectivi-
H
Ph
Ph
N
H N
NH2
N
2
X
DMF / HgO
10ºC
1
1
4,15
ties only being obtained in a few cases.
7a X=Br 72% (48h)
b X=F 92% (0.5h)
7
Ligands containing heteroatoms other than phosphorus
have occasionally been used successfully in the metal-
1
6
17
catalyzed reduction of C@N. Pfaltz and co-workers
Ph
Ph
H
reported enantioselectivities as high as 89% in the reduc-
tion of acyclic imines when cationic Ir(I) complexes with
diphenylphosphinooxazolines 1 were used (R = Pr,
Ar = o-Me–Ph, Fig. 1). This is one of the most success-
ful examples of cationic precursors in the asymmetric
hydrogenation of imines and it prompted us to try using
phosphine–imidazoline ligands in the iridium-catalyzed
enantioselective reduction of prochiral imines.
N
KPPh2 /THF
reflux, 1h
7
b
N
i
PPh2
9
9%
8
Ph
Ph
H
N
Ir(cod)2 BF4
Here we report a new and efficient procedure for synthe-
sizing chiral imidazolines based on the reaction of
dithioesters with enantiopure diamines, the synthesis
of phosphino imidazoline ligand 8, the corresponding
iridium complex and its behavior as a catalyst precursor
in the hydrogenation of imines.
N
P
BF4
Ir
2
CH Cl2
Ph Ph
9
Scheme 2.
2
. Results and discussion
Dithioesters 6a and b were prepared from benzoyl chlo-
rides 5a and 5b, which have a bromine or fluorine atom
at the ortho-position. Thus, the reaction of 5a and b with
sodium methanethiolate afforded 2-halo-thiobenzoic
acid (S)-methyl esters in almost quantitative yields,
which were subsequently treated with LawessonÕs rea-
gent to give dithioesters 6a and b in excellent yields
1
The H NMR spectra of complex 9 showed signals for
the methylene protons of the cyclooctadiene ligand
2
1
at the expected chemical shift (1.25–2.38ppm). The
olefinic protons of COD had two sets of signals. Two
olefinic protons appeared as broad peaks at 4.14–
5.12ppm, and the other two olefinic protons appeared
1
8
3
13
1
(
Scheme 2).
at 2.77–3.41ppm. In the C{ H} NMR spectra, the
C@N was shifted to a higher chemical shift than the
corresponding resonance in the free ligand. This obser-
Condensation of dithioesters 6a and b with (1R,2R)-
diphenylethylene diamine in the presence of HgO gave
2
2
vation is strong evidence of an M–N coordination.
7
31
1
2
-aryl-imidazolines 7a and b. The driving force of the
The P{ H} NMR spectra of 9 (15.5ppm) displayed a
singlet shifted to higher chemical shift than in the free
ligand 8 (ꢀ10.3ppm), which confirmed that the
phosphorus atom was coordinated to the metal
1
9
reaction is the precipitation of HgS. Therefore, com-
pounds 7a and b were synthesized from 5a and b with
an overall yield of 65% and 86%, respectively.
1
7c,d
center.
The phosphino moiety was introduced starting from 7b
d,20
9
following reported procedures.
with Ph PK in refluxing THF for an hour, which
We then reacted 7b
The analysis of the single crystal X-ray structure of 9
confirmed the expected organometallic nature of the
compound. The elementary cell of crystal of 9 contains
two independent molecules (A and B), which have the
same chirality and are related by pseudosymmetry.
The structures obtained are shown in Figure 2. The
independent molecules differ in the conformation of
the phosphorus atom, which can be located on the left
or the right of the plane of the imidazole ring.
2
afforded the phosphine–imidazoline ligand 8 in 99%
7
4
yield. The reaction of ligand 8 with [Ir(g -COD) ]BF
2
4
(
COD = cyclooctadiene) in dichloromethane gave the
4
complex [Ir(g -COD)8]BF 9. The FAB MS analysis
4
of 9 showed peaks at m/z 783.1 and 675.0, correspond-
+
4
+
ing to M of cation [Ir(g -COD)8] , and the loss of
+
cyclooctadiene (M ꢀCOD).

E. Guiu et al. / Tetrahedron: Asymmetry 15 (2004) 3365–3373
3367
We then explored the catalytic behavior of Ir(I)/phos-
phine–imidazoline catalysts with systems generated
4
4
in situ from [Ir(g -COD)Cl] or [Ir(g -COD) ]BF and
2
2
4
8 in order to evaluate the influence of the catalytic
precursor.
Three different imines were chosen as model substrates:
the acyclic imines N-(phenylethylidene)benzylamine 10
and N-(phenylethylidene)aniline 11, and the cyclic imine
6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline 14, in
which the geometry of the C@N double bond is fixed
in the E-configuration (Scheme 3).
For the reduction of acyclic imines 10 and 11, the cata-
4
lytic systems prepared in situ and based on [Ir(g -
Figure 2. Crystal structure of 9 (molecule A left and B right).
Hydrogen atoms, except those attached to chiral atoms, are omitted
for clarity.
COD) ]BF /8 provided better activity than the
2
4
4
precursors based on the dinuclear [Ir(g -COD)Cl] /8
2
(
Table 2, entries 2 and 4 vs 1 and 3), although enantio-
selectivity was negligible for imine 10 and very low for
imine 11.
The coordination geometry of the iridium atom in both
molecules is square planar, since the midpoints of the
double bonds of the COD ligands, the metal, and the
P and N atoms all lie on a plane (main deviation from
In the hydrogenation of imine 10, and in addition to the
secondary amine 12, hydrogenolysis products were also
detected, because of the cleavage of the nitrogen–benzy-
˚
plane molecule A: 0.0264A and molecule B:
16b
2
6
˚
.0035A). The phenyl substituents on the phosphorus
lic bond, which decreased selectivity (Table 2, entries 1
and 2).
0
adopt a pseudoequatorial and a pseudoaxial position as
expected by comparison with the Ir–phosphine–oxazo-
1
7c,d,23
3
It has been reported that using additives in the hydro-
2
genation of imines improves the enantioselectivity,
line
and Ir–phosphine–imidazoline complexes.
7,28
˚
The Ir–N distance [molecule A: 2.084(11) A; molecule B:
mainly when neutral precursors are used. However, in
our case the cationic precursors provide better conver-
sions, and we decided to explore the role of additives
with these precursors.
˚
.095(11) A] is shorter than the Ir–P distance [molecule
2
A: 2.267(4) A; molecule B: 2.279(4) A]. The distance
˚
˚
24
from the metal to the midpoint of the C(5)@C(6) double
bond trans to P [molecule A: 2.083(15) A; molecule B:
˚
˚
.102(12) A] is significantly longer than the distance
Many authors have reported the advantages of using
9
2
2
additives, particularly iodine, although there are also
examples of the use of amines or alcohols with both rho-
from the metal to the midpoint of the C(1)@C(2) double
bond trans to N [molecule A: 2.010(13) A; molecule B:
˚
2
7a,29b
˚
.992(13) A]. This indicates a clear trans effect, which
dium- and iridium–phosphine systems.
Neverthe-
1
2
4
less, additives do not always have a beneficial role; the
Ir-BINAP catalyst, for instance, is not affected by the
is also observable for similar Ir/NP and Pd/NP com-
plexes. In both molecules, the rings of the chelating lig-
and (phenyl and imidazoline rings) are not coplanar, but
slightly tilted, as indicated by the torsion angle of ꢀ27.0ꢁ
3
0
addition of iodide.
3
1
Suitable halides, or other additives, which can coordi-
nate to the vacant site of the iridium complex must be
selected to improve the enantioselectivity in the hydro-
(
in molecule A) and 45.2ꢁ (in molecule B). These values
are similar to those reported by Pfaltz and co-workers
3
for a similar iridium complex.
2
7,32,33
genation of imines.
ammonium iodide, benzylamine, and phthalimide as
We selected iodine, tetrabutyl-
The absolute configuration for both molecules was
2
5
additives in the hydrogenation of 11.
determined with R(C(9)); R(C(10)). Table 1 shows a
selection of bond lengths and angles for molecules A
and B of complex 9.
R
R
˚
Table 1. Selected bond distances (A) and angles (ꢁ) for complex 9
N
HN
Ph
Molecule A
Molecule B
Ph
*
Ir(1)ꢁ ꢁ ꢁ[C(1)–C(2)]
Ir(1)ꢁ ꢁ ꢁ[C(5)–C(6)]
Ir(1)–N(1)
2.010(13)
2.083(15)
2.084(11)
2.267(4)
1.368(17)
1.34(2)
1.992(13)
2.102(12)
2.095(11)
2.279(4)
1.378(17)
1.373(19)
1.291(16)
1.340(14)
84.8(3)
10 R=Bn
11 R=Ph
1
2 R=Bn
[
Ir] / L
13 R=Ph
[H2]
MeO
MeO
MeO
MeO
Ir(1)–P(1)
C(1)–C(2)
N
NH
C(5)–C(6)
N(1)–C(11)
*
1.337(17)
1.323(15)
87.0(3)
1
4
15
N(2)–C(11)
N(1)–Ir(1)-P(1)
Scheme 3.

3368
E. Guiu et al. / Tetrahedron: Asymmetry 15 (2004) 3365–3373
4
a
Table 2. Hydrogenation of imines 10, 11 and 14 with the catalytic system [Ir(g -COD)8]BF
4
b
c
Entry
Imine
Ligand
Precursor
Additive
Conv (%)
Selec (%)
Ee (%)
4
1
2
3
4
5
6
7
8
10
10
11
11
11
11
11
11
14
8
8
8
8
8
8
8
8
8
[Ir(g -COD)Cl]
2
—
—
—
—
27
48
2
28
64
9 (+)
3 (+)
22 (ꢀ)
15 (ꢀ)
24 (+)
0
4
[Ir(g -COD)
2
]BF
4
4
[Ir(g -COD)Cl]
2
100
100
100
100
100
99
4
[Ir(g -COD)
2
2
2
2
2
2
]BF
]BF
]BF
]BF
]BF
]BF
4
4
4
4
4
4
100
6
4
[Ir(g -COD)
4
Bu NI
4
[Ir(g -COD)
I
2
100
99
92
32
4
[Ir(g -COD)
Phthalimide
12 (ꢀ)
13 (ꢀ)
34 (ꢀ)
4
[Ir(g -COD)
BnNH
—
2
d
4
9
[Ir(g -COD)
100
a
b
c
1
mol% [Ir], 1.25mol% ligand, 4mol% additive, 70bar H
2 2 2
, CH Cl , 25ꢁC, 16h.
Selectivity = % of amine in the total products obtained.
No absolute configuration was determined.
d
6
2
0bar H , 18h.
The addition of Bu NI induced a sharp decrease in the
4
the substituent at the aminic nitrogen on the structure
of palladium complexes and in the stereoselectivity of
conversion and promoted the formation of the opposite
enantiomer (Table 2, entry 5), whereas adding I to the
4
CO/styrene copolymerization. A remarkable influence
of the electronic effects in the ligand in the enantioselec-
2
catalytic system gave racemic products (Table 2, entry
6
ꢀ
6
). Hence, the cationic Ir(I)/phosphine–imidazoline/I
systems did decrease the enantioselectivity of the proc-
ess. This behavior has already been reported by Pfaltz
tivity of the diethylzinc addition to aldehydes, and in the
7
Heck reaction has also been observed.
1
7c
and co-workers in the reduction of C@N with cati-
onic Ir(I)/diphenylphosphino-oxazolines catalysts, in
Accordingly, we decided to prepare diphenylphosphine–
imidazoline derivatives with donor or withdrawing
groups at the aminic nitrogen. Initially, we reacted 7b
with NaH/BnBr to obtain the benzyl derivative, which
was slightly impure due to some the starting material.
which the addition of Bu NI also decreased the ee and
4
reversed the configuration of the final product.
The addition of phthalimide or benzylamine did not
have a strong influence on either conversion or enantio-
selectivity (Table 2, entries 7, 8). The catalytic systems
Ir(I)/8/amine afforded complete conversions, demon-
strating that in this particular case the strong coordina-
tive amines are not poison for the catalyst.
The reaction of this mixture with KPPh provided 17
2
in moderate yield (Scheme 4). We tried the reaction of
8 with NaH/BnBr to obtain 17 obtaining similar results.
Several unsuccessful attempts at purifying 17 were made
and the final product contained traces of the starting
material. Reaction of 8 with trifluoroacetic anhydride
provided 16 in excellent yield.
4
Four different metal precursors were tested, [M(g -
4
COD)Cl] and [M(g -COD) ]BF (M = Ir and Rh) in
Reduction of 10 with the catalytic system [Ir(COD)2]-
BF /16 also afforded moderate yields and selectivities,
2
2
4
the reduction of cyclic imine 14. Conversions were very
low (<10%) with both rhodium precursors and the neu-
tral iridium precursor. The hydrogenation of 14 with the
catalytic system [Ir(COD) ]BF /8 in the same reaction
4
the ee being very low (Table 3, entries 1 and 2). Also
in this case, cationic precursors gave better conversions
than neutral ones (Table 3, entries 2 and 4 vs 1 and 3).
2
4
conditions as the imines 10 and 11, provided a modest
conversion and an ee of 34% (entry 9).
Ph
Ph
Ph
Ph
H
R
It has been shown that modifying the electronic proper-
ties of ligands can have dramatic effects on the enantiose-
N
N
N
N
3
4
lectivity in metal-catalyzed reactions. An important
difference (apart from the basicity) between the oxazoline
and imidazoline ring is that the imidazoline unit makes it
possible to introduce a variety of substituents into the
aminic nitrogen, which modify its electronic properties
X
PPh2
7
b X=F
8 X=PPh
16 R=CF3
17 R=Bn
2
(
Fig. 3). We have demonstrated the strong influence of
Scheme 4.
group that make it possible to
modify the electronic properties
R2
O
N
X
N
X
N
X=P, S, N
R1
R1
oxazoline/imidazoline ring
provides the enantio control
Figure 3.

E. Guiu et al. / Tetrahedron: Asymmetry 15 (2004) 3365–3373
3369
4
a
Table 3. Hydrogenation of imines 10, 11 and 14 with the catalytic system [Ir(g -COD)16,17]BF
4
b
c
Entry
Imine
Ligand
Precursor
Additive
Conv (%)
Selec (%)
Ee (%)
4
1
2
3
4
5
6
7
8
10
10
11
11
11
11
11
11
14
14
16
16
16
16
16
16
16
16
16
17
[Ir(g -COD)Cl]
2
—
—
—
—
44
75
38
83
11 (+)
5 (+)
4
[Ir(g -COD)
2
]BF
4
4
[Ir(g -COD)Cl]
2
14
100
100
100
100
100
99
14 (ꢀ)
51 (ꢀ)
27 (+)
4 (+)
4
[Ir(g -COD)
2
]BF
2
]BF
2
]BF
2
]BF
2
]BF
2
]BF
2
]BF
4
4
4
4
4
4
4
100
81
4
[Ir(g -COD)
4
Bu NI
4
[Ir(g -COD)
I
2
100
100
100
42
4
[Ir(g -COD)
Phthalimide
48 (ꢀ)
24 (ꢀ)
26 (ꢀ)
9 (ꢀ)
4
[Ir(g -COD)
BnNH
—
2
d
4
9
[Ir(g -COD)
100
100
4
10
[Ir(g -COD)
—
23
a
b
c
1
mol% [Ir], 1.25mol% ligand, 4mol% additive, 70bar H
2
2 2
, CH Cl , 25ꢁC, 16h.
Selectivity = % of amine in the total products obtained.
No absolute configuration was determined.
d
6
2
0 bar H , 18h.
However, when ligand 16 was used, imine 11 was re-
duced with total conversion and selectivity with the
enantiomeric excess being 51% (entry 4). Interestingly,
3. Conclusions
In conclusion, we have established a very efficient proce-
dure for synthesizing 2-aryl-imidazolines by reacting
aryldithioesters with chiral diamines. These imidazolines
were used in the synthesis of phosphine–imidazoline lig-
ands 8, 16, and 17.
when the withdrawing group CF CO was introduced
3
at the iminic nitrogen, the ee increased from 15% (Table
2
, entry 4) to 51% (Table 3, entry 4).
Studies in the hydrogenation of enamidoacids using
phosphorus ligands have shown that the ee increases
when electron-donating groups are present in the ligand.
This has been attributed to the fact that electron-rich
phosphines, and phosphinites, increase the rate of the
oxidative addition (usually the rate limiting step) in
the less stable diastereomer by increasing the energy
Catalytic systems formed in situ by the iridium precur-
4
sor [Ir(g -COD) ]BF in the presence of the phos-
2
4
phine–imidazoline ligands 8, 16, and 17, hydrogenate
acyclic and cyclic imines provided moderate eeÕs. In gen-
eral, the additives had a negative effect on the enantiose-
lectivity of the cationic iridium catalyst based on NP
ligands, although the catalyst did not lose its activity
when strong coordinative compounds such as amines
were added. The electronic properties of the imidazoline
moiety, determined by the substituent on the amine
group, strongly influence the enantioselectivity obtained
in the reduction of imine 11.
3
4a,b
level of the dyz orbital.
In the case of imine hydro-
genation with ligands 8, 16, and 17 we observed an
increase in the enantioselectivity when withdrawing
groups were used. A mechanism of imine hydrogenation
with iridium complexes based on kinetic studies suggests
that the rate limiting step is the first hydride transfer to
1
35
give the g -N–Ir intermediate. Possible reasons to
explain the results obtained can be the stabilization of
1
the g -N–Ir bond, and/or conformational changes
4. Experimental
in the ligand induced by the trifluoroacetyl group. In
fact, the imidazoline and the phenyl group are not
coplanar (see Fig. 2), and the torsion angle must be
influenced by the substituent at the aminic nitrogen.
All reactions were carried out under an argon atmos-
phere using standard Schlenk techniques. Solvents were
1
distilled and degassed prior to use. H,
13
1
C{ H},
3
1
1
19
P{ H}, and F{ H} NMR spectra were recorded on
1
Additives have a similar influence to that of the catalytic
system [Ir(COD) ]BF /8 (Table 2, entries 5–8, Table 3
a Varian Gemini spectrometer at 300 and 400MHz.
Chemical shifts were reported relative to tetramethylsi-
2
4
1
13
1
entries 5–8). Thus, the addition of tetrabutylammonium
iodide decreased the conversion, although less so than
with ligand 8, and inverted the sign of the main enantio-
mer obtained. The use of iodine provided the racemate
while the phthalimide did not have a strong influence
on either conversion or enantioselectivity. The catalytic
systems Ir(I)/16/amine afforded complete conversions.
However, a considerable decrease in the ee was observed
when benzylamine was added (Table 3, entry 8).
lane for H and C{ H} as internal reference, H PO
3 4
3
1
1
P{ H}, and trichlorofluoromethane for
85% for
F{ H} as external references. Elemental analyses were
1
9
1
carried out on a Carlo Erba Microanalyser EA 1108.
VG-Autospect equipment was used for FAB mass spec-
tral analyses with 3-nitrobenzylalcohol as matrix. EI
mass spectra were obtained on an HP 5989 A spectro-
meter at an ionizing voltage of 70eV. Optical rotations
were measured on a Perkin–Elmer 241 MC polarimeter.
Melting points were determined in an open capillary
tube with a Tottoli-B u¨ chi 510 melting point apparatus
and are uncorrected. Single hydrogenation reactions
were carried out in a Berghof or Parr 100mL stainless
steel autoclave and multi-screening hydrogenations were
performed in a home-made 96-microtiter plate in Bayer
AG (Leverkusen–Germany). The catalytic reactions
4
Reduction of imine 14 with the catalytic system [Ir(g -
COD) ]BF /16 gave a modest conversion and an ee
lower than that obtained with ligand 8 (Table 3, entry
2
4
2
7
9
).
In this case, we tested the catalytic system
4
[Ir(g -COD) ]BF /17 that contained the most electron-
rich ligand, which gave a very low ee (entry 10).
2
4

3370
E. Guiu et al. / Tetrahedron: Asymmetry 15 (2004) 3365–3373
1
arom.), 2.71 (s, 3H, CH3); C NMR (100.6MHz;
3
were monitored by GC on a Hewlett–Packard 5890A.
Conversion was measured in an Ultra-2 (5% diphenylsili-
cone/95% dimethylsilicone) column (25m · 0.2mm Ø).
The enantiomeric excesses were measured directly in
the reaction crude by NMR or gas chromatography.
N-(Phenylethylidene) benzylamine 12 was determined
1
CDCl ) d 224.2 (C@S), 157.3 (d, J(C–F) 253.1Hz, C,
3
2
arom.), 134.5 (d, J(C–F) 12.4Hz, C, arom.), 132 (d,
3
J(C–F) 8.5Hz, CH, arom.), 129.5 (CH, arom.), 123.9
(d, J(C–F) 3.7Hz, C, arom.), 116.3 (d, J(C–F)
22.2Hz, CH, arom.), 20.9 (CH3).
3
2
1
by H NMR (with mandelic acid as the resolution agent)
or by GC, after derivation into the trifluoroacetamide
compound, in a b-cyclodextrin phase. The enantiomeric
excess of N-(phenylethylidene)aniline 13 and 6,7-
dimethoxy-1-methyl-3,4-dihydroisoquinoline imine 15
was determined by CC, after derivation into the acet-
amide compound, in a MN, Hydrodex–6-TBDM
4.3. Synthesis of (4R,5R)-2-(2-bromo-phenyl)-4,5-diphen-
7
yl-4,5-dihydro-1H-imidazole 7a
A solution of 6a (914mg, 3.7mmol) in dimethylform-
amide (4mL) was added to a suspension of (1R,2R)-
diphenylethylenediamine (786mg, 3.7mmol) and red
mercury(II) oxide (814mg, 3.7mmol) in dimethylform-
amide (9mL) at room temperature and vigorously stir-
red. The solution was heated at 110ꢁC for 48h. Then,
the reaction mixture was filtered, concentrated under re-
duced pressure, and purified by flash column chroma-
tography (hexane/ethyl acetate 1:7) to afford 1g (72%
yield) of compound 3a as a white powder. Mp = 148–
(
25m · 0.25mm · 0.25m) column.
4.1. Synthesis of 2-bromo-dithiobenzoic acid (S)-methyl
ester 6a
2
-Bromobenzoylchloride (186lL, 1.42mmol) was added
dropwise at 0ꢁC to a suspension of 0.12g (1.6mmol) of
methanethiolate sodium salt with 1.5mL of dichloro-
methane. After 1h at room temperature, the reaction
mixture was quenched with water (5mL). After several
extractions with dichloromethane, the combined organic
layers were dried and concentrated to afford 2-bromo-
thiobenzoic acid (S)-methyl ester as a yellow liquid
2
0
1
150ꢁC. ½aꢂ = +60.1 (c = 1.07, CH Cl ). H NMR
D
2
2
(400MHz, CDCl ) d 7.72 (m, 1H, arom.), 7.59–7.57
3
(m, 1H, arom.), 7.35–7.24 (m, 12H, arom.), 4.83 (s,
1
3
2H, CH); C NMR (100.6MHz, CDCl ) d 163.1
3
(C@N), 143.2 (CH, arom.), 133.4 (CH, arom.), 132.6
(C, arom.), 131.5 (CH, arom.), 131.4 (CH, arom.),
129.2 (C, arom.), 128.7 (CH, arom.), 128.4 (CH, arom.),
127.6 (CH, arom.), 127.1 (CH, arom.), 126.8 (CH,
arom.), 121.1 (C, arom.), 75.3 (CH). Elemental analysis:
Calcd for C H BrN : C, 67.34; H, 4.58; N, 7.44.
(
0.325g), which was used without purification in the
next step. Next, LawessonÕs reagent (2g, 5.4mmol)
was added under argon to a solution of 2-bromo-thio-
benzoic acid (S)-methyl ester (0.325g, 1.4mmol) in dry
toluene (17mL) and the mixture heated to reflux. The
reaction was monitored by TLC. When no starting
material could be detected (ca. 24h), the reaction mix-
ture was allowed to cool and filtered. The solid was
washed with toluene and the combined toluene solutions
were evaporated, and purified by flash column chroma-
tography (hexane/ethyl acetate 10:1) to afford 318mg
2
1
17
2
Found: C, 67.22; H, 4.60; N, 7.46.
4.4. Synthesis of (4R,5R)-2-(2-fluoro-phenyl)-4,5-diphen-
7
yl-4,5-dihydro-1H-imidazole 7b
Using a procedure that was identical to that for 7a,
starting from 6b (326mg, 1.75mmol), dimethylform-
(
91% yield for the two steps) of compound 6a as a red
amide
(3mL),
(1R,2R)-diphenylethylenediamine
1
liquid. H NMR (400MHz; CDCl ) d 7.57 (m, 1H,
(407mg, 1.92mmol), and red mercury(II) oxide
(414mg, 1.9mmol) in dimethylformamide (2mL) were
reacted at 110ꢁC for 30min. Work-up of the reaction
mixture afforded compound 7b (509mg, 92%).
3
arom.), 7.35–7.20 (m, 3H, arom.), 2.78 (s, 3H, CH );
C NMR (100.6MHz; CDCl ) d 230.4 (C@S), 147.7
3
1
3
3
(
C, arom.), 133.6 (CH, arom.), 130.4 (CH, arom.),
20
1
1
2
28.2 (CH, arom.), 127.4 (CH, arom.), 118.6 (C, arom.),
0.9 (CH3).
½aꢂ = +48.5 (c = 0.811, CH Cl ). H NMR (400MHz,
D
2
2
CDCl ) d 8.28 (dt, 1H, J = 7.6Hz, J = 1.6Hz, arom.),
3
7
.49–7.12 (m, 13H, arom.), 5.99 (s, 1H, NH), 4.89 (s,
1
3
4.2. Synthesis of 2-fluoro-dithiobenzoic acid S-methyl
ester 6b
2H, CH); C NMR (100.6MHz, CDCl ) d 162.1
3
1
(C@N), 159.4 (d, J = 32.9Hz, C, arom.), 143.3 (C,
arom.), 132.6 (d, J = 9.15Hz, CH, arom.), 131.3 (d,
3
4
Using a procedure that was identical to that for 6a, 2-
fluorobenzoylchloride (1.9mL, 15.5mmol) was added
dropwise at 0ꢁC to a suspension of sodium methanethio-
late salt (1265g, 17mmol) in 15mL of dichloromethane.
J = 2.3Hz, CH, arom.), 128 (CH, arom.), 127.5 (CH,
arom.), 126.6 (CH, arom.), 124.6 (d, J = 3.1Hz, CH,
3
2
arom.), 117.6 (d, J = 10.6Hz, C, arom.), 116.1 (d,
2
J = 23.6Hz, CH, arom.); dF (376.5MHz; solvent
+
2
-Fluoro-thiobenzoic acid (S)-methyl ester was obtained
CDCl ; standard CFCl ) ꢀ114.2 (m); m/z 316 (M ,
3
3
as a yellow liquid (2.6g), which was used without purifi-
cation in the next reaction step. Next, LawessonÕs rea-
gent (13.9g, 37.5mmol) was added under argon to a
solution of 2-fluoro-thiobenzoic acid (S)-methyl ester
11.3%), 239 (1.28), 211 (100); HRMS: m/z, C H N F
21 17 2
calculated: 316.1376, Found: 316.1365. Elemental analy-
sis: Calcd for C H FN : C, 79.72; H, 5.42; N, 8.85.
Found: C, 80.10; H, 5.32; N, 8.95.
2
1
17
2
(
was heated to reflux for 24h to give compound 6b as a
2.6g, 15.2mmol) in dry toluene (17mL) and the mixture
4.5. Synthesis of (4R,5R)-2-(2-diphenylphosphanyl-phen-
7
yl)-4,5-diphenyl-4,5-dihydro-1H-imidazole 8
red liquid (2.76g, 94% for the two steps). The obtained
product was pure enough to be used in the next reaction
1
without purification. H NMR (400MHz; CDCl ) d 7.56
Compound 7b (150mg, 0.475mmol) was added to a
solution of potassium diphenylphosphide (1.04mL,
3
(
m, 1H, arom.), 7.34 (m, 1H, arom.), 7.13–7.03 (m, 2H,

E. Guiu et al. / Tetrahedron: Asymmetry 15 (2004) 3365–3373
3371
0
.522mmol, 0.5M in tetrahydrofuran) and the resulting
XP program. The missing atoms were subsequently
located by difference Fourier synthesis and added to
the atom list. The elementary cell contains two indepen-
dent molecules of complex 9 related by pseudosymme-
try. Least-squares refinement on F2 using all measured
intensities was carried out with the program SHELXTL
Version 6.10 (Sheldrick, Universtit a¨ t G o¨ ttingen (Ger-
many), 2000). All nonhydrogen atoms were refined,
including anisotropic displacement parameters. The
benzene ring C12A–C17A is disordered, without effects
on the chirality, in two positions with a ratio 81:19.
Hydrogen atoms were invariably placed in geometrically
optimized positions and forced to ride on the atom to
which they are attached. A structure solution in the centro-
mixture heated at 60ꢁC for 1h. The reaction crude was
then poured into water and extracted twice with dichlo-
romethane. The organic layer was dried with anhydrous
MgSO and purified by column chromatography under
4
argon (hexane/ethyl acetate 1:1) to give compound 8
20
as a white foam (226mg, 99%). ½aꢂ = ꢀ19.2 (c = 0.57,
D
1
CH Cl ); H NMR (400MHz, CDCl ) d 7.80 (m, 1H,
2
2
3
arom.), 7.32–7.11 (m, 22H, arom.), 6.80 (m, 1H, arom.),
5
CH); C NMR (100.6MHz, CDCl ) d 164.2 (C@N),
1
(161.9MHz, CDCl , standard H PO 85%) d ꢀ10.3;
MS: m/z 482 (M , 3.78%), 405 (9.61), 301 (100), 222
.86 (br s, 1H, NH), 4.73 (m, 1H, CH), 4.48 (m, 1H,
1
3
3
3
43.3–126.7 (arom), 80.3 (CH), 71.3 (CH); P NMR
1
3
3
4
+
(
3.59); HRMS (EI): m/z, C H N P Calculated
2
symmetrical space group P2 /c is also possible and leads
1
3
3
27
4
82.1912, Found 482.1911. Elemental analysis: Calcd
for C H N P: C, 82.14; H, 5.64; N, 5.81. Found: C,
after refinement to a single molecule in the elementary
cell with disorder at the phenyl rings attached to the chi-
ral centers (C12–C17 and C18–C23). The occupancy of
the disordered atoms is 50:50. By solving and refining
the structure in the centrosymmetrical space group
3
3
27
2
8
2.17; H, 5.48; N, 5.29.
4
4
.6. Synthesis of [Ir(g -COD)(8)]BF 9
4
P2 /c the absolute configuration cannot be determined
1
A solution of 8 (81.7mg, 0.17mmol) in dry and degassed
dichloromethane (3mL) was added dropwise to a chilled
and the R value is much higher. The structure solution
1
in the chiral space group P2 should be preferred. The
1
structure determination was repeated a second time with
a new crystal and the results were the same as those of
the first crystal measured.
4
(
0
ꢀ80ꢁC) solution of [Ir(g -COD) ]BF
(70mg,
.141mmol) in dry and degassed dichloromethane
2
4
(3.5mL). The solution was allowed to warm to 0ꢁC
and stirred for 30min. Then, ethyl ether (30mL) was
added to precipitate the desired product 9 as a pale
red orange solid (119mg, 97%). H NMR (400MHz,
4.8. Crystal data
1
CDCl ) d 8.50–6.70 (m, 24H, CH arom.), 4.93 (m, 1H,
(C H BF N PIr) · 2, M = 869.72, monoclinic, space
3
41 39
4
2
˚ ˚
group P2 (no. 4), a = 13.8464(7) A, b = 13.5639(6) A,
1
CH), 4.85 (m, 2H, CH, COD), 4.66 (m, 1H, CH), 2.90
(
3
˚
˚
m, 1H, CH, COD), 2.77 (m, 1H, CH, COD), 2.37 (m,
c = 19.0698(8) A, b = 98.779(2)ꢁ, V = 3539.6(3) A ,
ꢀ3
ꢀ1
1
3
H, CH , COD), 2.14 (m, 1H, CH , COD), 2.03 (m,
2
Z = 2, q
= 1.632gcm , l = 3.871mm , F(000) =
1728, Reflections collected = 52,629, independent reflec-
2
calc.
H, CH , COD), 1.67 (m, 1H, CH , COD), 1.48
2
2
1
3
(
m, 2H, CH , COD); C NMR (100.6MHz, CDCl ) d
tions [R(int)] = 22,446 [0.1091], observed reflections
Fo > 4r (Fo) = 7380, Data/restraints/parameters =
2
3
1
62.2 (C@N), 141.9–125.4 (arom.), 95.6 (CH, COD),
3.2 (CH, COD), 78.8 (CH), 67.5 (CH), 59.8 (CH,
2
22,446/43/896, goodness-of-fit on F = 0.864, final R
9
COD), 59.5 (CH, COD), 34.4 (CH , COD), 31.5 (CH ,
1
[I > 2r(I)] = 0.0661, final wR2 [all data] = 0.1336,
absolute structure parameter: ꢀ0.003(10). CCDC No.
230095.
2
2
3
COD), 29,8 (CH , COD), 27.5 (CH , COD); P NMR
1
2
2
(
m/z 783.1 (M , 100%). HRMS L-SIMS: m/z,
161.9MHz, CDCl , standard H PO 85%) 15.5;
3 3 4
+
+
C H N PIr] Calculated 783.2480, Found 783.2467.
[
4.9. Synthesis of (4R,5R)-1-trifluoroacetyl-2-(2-diphenyl-
phosphanyl-phenyl)-4,5-diphenyl-4,5-dihydro-1H-imidaz-
ole 16
4
1
39
2
4
.7. Crystal structure determination of complex 9
Single crystals of 9 were recrystallized under inert condi-
tions from 2-butanone at room temperature. An orange
crystal plate with the dimensions 0.20 · 0.20 · 0.01mm
A total of 45lL (0.31mmol) of trifluoroacetic anhydride
was added to a solution of 100mg (0.207mmol) of 8 and
60lL of triethylamine in 1mL of anhydrous dichloro-
methane. The solvent was removed after 1h and the resi-
due purified by silica gel column chromatography under
argon (hexane/ethyl acetate 5:1) to give compound 16 as
3
was used to take the measurements. The crystal struc-
ture for 9 was determined using a Siemens P4 diffrac-
tometer equipped with a SMART-CCD-1000 area
detector, a MACScience Co rotating anode with MoK
radiation, a graphite monochromator, and a Siemens
low temperature device LT2 (T = ꢀ120ꢁC). The mea-
surements were made in the range 1.70–31.55ꢁ for h.
Fullsphere data collection omega and phi scans. Pro-
grams used: Data collection Smart V. 5.060 (BrukerAXS
1
a white solid (102.8mg, 86%). H NMR (400MHz;
CDCl ) d 7.60 (ddd, J = 8Hz, J = 4.4Hz, J = 3Hz, 1H,
3
arom.), 7.47 (dt, J = 7.6Hz, J = 0.8Hz, 1H, arom.),
7.41–7.20 (m, 19H, arom.), 7.11 (ddd, J = 7.6Hz,
J = 4Hz, J = 0.8Hz, 1H, arom.), 7.15 (t, J = 1.2Hz,
1H, arom.), 7.00 (d, J = 2.4Hz, 1H, arom.), 5.28 (d,
3
1
3
1
1
999), data reduction Saint+Version 6.02 (Bruker AXS
999) and absorption correction SADABS (Bruker
J = 4.6Hz, 1H, CH), 5.16 (d, J = 4.6Hz, 1H, CH);
C NMR (100.6MHz; CDCl ) d 165.8 (C@N), 155.1
3
3
2
(d, J
AXS1999). Thecrystal structuresolutionfor 9in thespace
group P2 was achieved using the direct methods imple-
= 39.8Hz, C@O), 141–125 (arom), 115.4 (d,
JC–F = 289.1Hz, CF ), 81.4 (CH), 70.0 (CH); dP
C–F
1
1
3
mented in SHELXTL Version 5.10 (Sheldrick, Universtit a¨ t
G o¨ ttingen (Germany), 1998) and visualized using the
(161.9MHz; solvent CDCl ; standard H PO 85%)
ꢀ11.8; d (376.5MHz; solvent CDCl ; standard CFCl )
3
3
4
F
3
3

3372
E. Guiu et al. / Tetrahedron: Asymmetry 15 (2004) 3365–3373
ꢀ
71.7. Elemental analysis: Calcd for C H F N OP: C,
3
2.66; H, 4.53; N, 4.84. Found: C, 72.63; H, 4.34; N,
.71.
2. Guiry, P. J.; Saunders, C. P. Adv. Synth. Catal. 2004, 346,
97.
. Menges, F.; Neuburger, M.; Pfaltz, A. Org. Lett. 2002, 4,
713.
. (a) Bastero, A.; Claver, C.; Ruiz, A.; Castill o´ n, S.; Daura,
E.; Bo, C.; Zangrando, E. Chem. Eur. J. 2004, 10, 3747; (b)
Bastero, A.; Ruiz, A.; Claver, C.; Castill o´ n, S. Eur. J.
Inorg. 2001, 3009.
5
26
3
2
4
7
4
3
4
4
4.10. Synthesis of (4R,5R)-1-benzyl-2-(2-diphenylphos-
phanyl-phenyl)-4,5-diphenyl-4,5-dihydro-1H-imidazole 17
A solution of 125mg (0.395mmol) of 7b in 1mL of anhy-
drous tetrahydrofuran was added to a cooled solution
5
. Davenport, A. J.; Davies, D. L.; Fawcett, J.; Russel, D. R.
J. Chem. Soc., Perkin Trans. 1 2001, 1500.
(
0ꢁC) of 17.4mg (0.43mmol) of NaH (60% in oil suspen-
6. Casey, M.; Smyth, M. P. Synlett 2003, 102.
7. Busacca, C. A.; Grossbach, D.; So, R. C.; OÕBrien, E. M.;
Spinelli, E. M. Org. Lett. 2003, 5, 595.
sion) and 0.5mL of anhydrous tetrahydrofuran. The
mixture was stirred for 30min and then benzyl bromide
8
9
. (a) Lin, Y.-R.; Zhou, X.-T.; Dai, L.-X.; Sun, J. J. Org.
Chem. 1997, 62, 1799; (b) Jones, R. C. F.; Howard, K. J.;
Snaith, J. S. Tetrahedron Lett. 1996, 37, 1707; (c) Hayashi,
T.; Kishi, E.; Soloshonok, V. A.; Uozumi, Y. Tetrahedron
Lett. 1996, 37, 4969.
(
47ll, 0.395mmol) added dropwise. After 3h, the reac-
tion was stopped by adding a few drops of methanol.
Purification by column chromatography (hexane/ethyl
acetate 3:1) gave compound 4 as a pale yellow solid
(
88.5mg, 55%). Several attempts of purification were
. (a) Hunter, M. J.; Ludwig, M. L. J. Am. Chem. Soc. 1969,
9
unsuccessful, and the final product contained 5% of start-
ing material. This mixture was added to a solution of
potassium diphenylphosphide (0.5M in tetrahydrofuran)
1, 2429; (b) Bristow, N. W. J. Chem. Soc. 1957, 513; (c)
Hartke, K.; Brutsche, A. Synthesis 1992, 1199; (d) Baati,
R.; Gouverneur, V.; Mioskowski, C. Synthesis 1999, 6,
927.
(
0.5mL, 0.239mmol) and heated at 60ꢁC for 1h. The
1
1
0. (a) Pinner, A.; Klein, F. Ber. 1877, 10, 1889; (b) Steinkopf,
W.; Malinowski, W. Ber. 1911, 44, 2898.
1. (a) Whelan, B.; Iriepa, I.; Galvez, E. Synthesis 1994, 832;
reaction crude was then poured into water and extracted
twice with dichloromethane. The organic layer was dried
with anhydrous MgSO and purified by column chroma-
4
(
b) Dauwe, C.; Buddrus, J. Synthesis 1995, 171; (c)
Morimoto, T.; Tachibana, K.; Achiwa, K. Synlett 1997,
83; (d) Helmchen, G.; Kudis, S.; Sennhenn, P.; Steinha-
tography under argon (hexane/ethyl acetate 3:1) to give
compound 17 as a white solid (68mg, 54%). Several
attempts of purification were unsuccessful and the final
product contained traces of 7b. H NMR (400MHz,
CDCl ) d 7.70 (m, 1H, arom.), 7.44 (m, 1H, arom.),
7
gen, H. Pure Appl. Chem. 1997, 69, 513.
2. Boland, N. A.; Casey, M.; Hynes, S. J.; Mattews, J. W.;
Smyth, M. P. J. Org. Chem. 2002, 67, 3919.
1
1
3
7
.38–7.10 (m, 25H, arom.), 6.90 (m, 2H, arom.), 4.93
d, J = 9.8Hz, CH), 4.44 (d, J = 9.8Hz, CH), 4.28 (d,
13. (a) Takaya, H.; Ohta, T.; Noyori, R.. In Catal. Asymmet-
ric Synth.; Ojima, I., Ed.; John Wiley: New York, 1993;
p 31, Chapter 1; (b) Blaser, H.-U.; Spindler, F. In
Comprehensive Asymmetric Catalysis; Jacobsen, E. N.,
Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999;
Vol. 1, p 247, Chapter 6.
3
3
(
2
2 13
J = 17Hz, CH ), 3.70 (d, J = 17Hz, CH ); C NMR
2
2
(
7
100.6MHz, CDCl ) d 164.9 (C@N), 143.9–126.8 (arom),
3
3
1
8.8 (CH), 72.8 (CH), 49.3 (CH ); P NMR (161.9MHz,
2
CDCl ) d ꢀ12.3; m/z 481 (100), 91 (26.11).
3
1
4. Reviews of asymmetric hydrogenation of C@C and C@N:
a) Spindler, F.; Blaser, H.-U. In Transition Metals for
(
4.11. General procedure for the Ir-catalyzed hydrogena-
tion of imines
Organic Synthesis; Beller, M., Bolm, C., Eds.; J. Wiley &
Sons: Weinhem, 1998; Vol. 2, p 69, Chapter 1; (b) Palmer,
M. J.; Wills, M. Tetrahedron: Asymmetry 1999, 10, 2045;
(c) Kobayashi, S.; Ishitani, H. Chem. Rev. 1999, 99, 1069;
(d) Blaser, H.-U.; Malan, C.; Pugin, B.; Spindler, F.;
Heinz, S.; Studer, M. Adv. Synth. Catal. 2003, 345, 103.
5. Margalef-Catal a` , R.; Salagre, P.; Fern a´ ndez, E.; Claver,
C. Tetrahedron: Asymmetry 2000, 11, 1469.
6. (a) Cahill, J. P.; Lightfoot, A. P.; Goddard, R.; Rust, J.;
Guiry, P. J. Tetrahedron: Asymmetry 1998, 9, 4307; (b)
Takei, I.; Nidhibayashi, Y.; Arikawa, Y.; Uemura, S.;
Hidai, M. Organometallics 1999, 18, 2271; (c) Cozzi, P. G.;
Menges, F.; Kaiser, S. Synlett 2003, 6, 833.
4
4
[
Ir(g -COD)Cl] (0.022mmol) or [Ir(g -COD) ]BF
2
2
4
(0.045mmol) was dissolved in 10mL of dry, degassed
CH Cl in a Schlenk tube. The phosphine–imidazoline
ligand (0.055mmol) was then added, followed by the
corresponding imine (4.4mmol for a 100:1 imine:Ir
ratio). The solution was transferred under argon to the
autoclave via a syringe. The reaction mixture was stirred
2
2
1
1
at room temperature under 70bar of H pressure.
2
1
7. (a) von Matt, V.; Pfaltz, A. Angew. Chem., Int. Ed. Engl.
1993, 32, 566; (b) Schnider, P.; Koch, G.; Pr e´ tot, R.;
Wang, W.; Bohnen, F. M.; Kr u¨ ger, C.; Pfaltz, A. Chem.
Eur. J. 1997, 3, 887; (c) Kainz, S.; Brinkmann, A.; Leitner,
W.; Pfaltz, A. J. Am. Chem. Soc. 1999, 121, 6421; (d)
Pfaltz, A. Chimia 2001, 55, 708.
Acknowledgements
Financial support by Bayer AG is acknowledged. Tech-
nical assistance from the Servei de Recursos Cientifics
(
URV) is acknowledged.
1
8. Montenegro, E.; Echarri, R.; Claver, C.; Castill o´ n, S.;
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