Tetrathiafulvalene-oxazoline ligands in the iridium catalyzed enantioselective hydrogenation of arylimines

Article abstract of DOI:10.1016/j.tetasy.2007.07.019

Cationic iridium complexes based on enantiomerically pure tetrathiafulvalene-oxazoline ligands have been used in the asymmetric hydrogenation of N-(phenylethylidene)aniline. Complete conversions with ee's up to 68% could be reached in the case of the TTF-

Full text of DOI:10.1016/j.tetasy.2007.07.019

Tetrahedron: Asymmetry 18 (2007) 1877–1882
Tetrathiafulvalene–oxazoline ligands in the iridium catalyzed
enantioselective hydrogenation of arylimines
a
a
a,
a,
*
C e´ line R e´ thor e´ , Fran c¸ ois Riob e´ , Marc Fourmigu e´ , Narcis Avarvari,
b
b,
*
Isabelle Suisse and Francine Agbossou-Niedercorn
a
Laboratoire de Chimie, Ing e´ nierie Mol e´ culaire et Mat e´ riaux d’Angers, UMR 6200, 2 Bd Lavoisier, 49045 Angers Cedex, France
b
Laboratoire de Catalyse de Lille, UMR 8010, ENSCL, BP 90108, 59652 Villeneuve d’Ascq Cedex, France
Received 5 July 2007; accepted 23 July 2007
Available online 24 August 2007
Abstract—Cationic iridium complexes based on enantiomerically pure tetrathiafulvalene–oxazoline ligands have been used in the asym-
metric hydrogenation of N-(phenylethylidene)aniline. Complete conversions with ee’s up to 68% could be reached in the case of the TTF–
phosphinooxazoline (TTF–PHOX) ligands.
ꢀ
2007 Elsevier Ltd. All rights reserved.
1
. Introduction
applied in industrial processes.9 Phosphine–oxazoline
ligands (PHOX) have also been found to be highly effective
for the Ir-catalytic enantioselective hydrogenation of imi-
Catalytic enantioselective hydrogenation of prochiral func-
tionalized alkenes and ketones has been extensively stud-
1
0
nes. Alternatively, ligands possessing an oxazoline ring
1
2
3
11
ied. Rhodium and ruthenium catalysts, coordinated by
chiral diphosphane ligands, are very efficient in such pro-
cesses. In most cases, the ee’s are excellent (>90%) and
the catalytic turnovers are amongst the highest of any
asymmetric process. On the other hand, catalytic asymmet-
ric hydrogenation of simple alkenes and imines is less
common and has been proven to be much more difficult
in terms of activity and stereoselectivity. Nevertheless, the
synthesis of enantiomerically pure amines remains a real
challenge because they are synthetic intermediates in many
biological active compounds. Classical catalysts based on
and a second functional group, such as a phosphinite,
a
1
2
13
thioether, or an amino-phosphine, have been synthe-
sized and used in the imine Ir-catalyzed hydrogenation.
Recently, some of us have reported on the synthesis of a
new class of electroactive ligands containing a methyl or
an isopropyl substituted oxazoline linked to an ethylenedi-
4
5
1
4
thio-tetrathiafulvalene core (EDT-TTF–OX), as well as
on their use as precursors for chiral molecular conduc-
1
5
tors. Functionalized precursors, bearing either phosphino
1
6
(EDT-TTF–PHOX) or thiomethyl groups (EDT-TTF–
6
17
Rh and Ru are often inefficient for this purpose. Buchwald
SMe–OX), thus providing potential chelating P,N or
has developed a Ti-catalyst, which has been successfully
applied for the hydrogenation of cyclic imines (ee’s up to
S,N ligands, have also been prepared (Scheme 1). The com-
i
pounds containing an Pr–oxazoline unit have been evalu-
1
8
9
9%). Finally, iridium complexes were found to be excel-
ated in the asymmetric allylic substitution reaction, with
lent catalysts for the hydrogenation of a large variety of
7
imines. Among the chiral auxiliaries evaluated so far,
the ferrocenyl Josiphos R PFerr-PR and derivates repre-
2
2
sent the most successful diphosphane ligands for the enan-
tioselective hydrogenation of imines, and have even been
0
8
O
O
S
S
iPr
S
S
iPr
S
S
S
S
S
S
S
S
N
N
X
X = PPh2, EDT-TTF-PHOX
i
*
Corresponding authors. Tel.: +33 2 41 73 50 84; fax: +33 2 41 73 54 05
N.A.); tel.: +33 20 43 49 27 (F.A.-N.); e-mail addresses:
EDT-TTF- Pr-OX
1a (± ±, 1b (R±, 1c (S±
2
a (± ±, 2b (R±, 2c (S±
(
3
X = SMe, EDT-TTF-SMe-OX
3a (R±, 3b (S±
narcis.avarvari@univ-angers.fr; francine.agbossou@ensc-lille.fr
Present address: Sciences Chimiques de Rennes, UMR 6226 CNRS-
Universit e´ Rennes I, Campus de Beaulieu, 35042 Rennes, France.
Scheme 1. TTF–OX, TTF–PHOX and TTF–SMe–OX ligands.
0957-4166/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.07.019

1878
C. R e´ thor e´ et al. / Tetrahedron: Asymmetry 18 (2007) 1877–1882
very good selectivities in the case of the TTF–PHOX
ligands.
structure. Both enantiomers crystallize in the monoclinic
non-centrosymmetric space group P2 , with two indepen-
1
dent molecules in the asymmetric unit. As in the case of
1
7
Herein we report on the evaluation of chiral ligands 1–3 in
the asymmetric hydrogenation of N-(phenylethylidene)ani-
line catalyzed by cationic iridium complexes.
the Me–oxazoline counterparts, the most striking struc-
tural feature consists of the occurrence of short intramolec-
˚
ular Sꢀ ꢀ ꢀO distances of 2.83–2.84 A within quasi planar
conformations, indicative of the establishment of 1,5 non-
bonded interactions (3b in Fig. 1).
2
. Results and discussion
i
14,16
The syntheses of EDT-TTF– PrOX 1a–c,
EDT-TTF–
i
i
16,18
PPh – PrOX 2a–c
and EDT-TTF–SMe– PrOX 3a–
have previously been described. Single crystal X-ray
2
7,18
1
b
analyses revealed that the twist angle between the TTF
and oxazoline moieties is close to 0ꢁ, thus leading to an
1
4
overall planar conformation of the compounds. More-
over, in the case of the EDT-TTF–SMe–Me–OX deriva-
tives, intramolecular OOXꢀ ꢀ ꢀS
1,5-non-bonded inter-
SMe
actions, characterized by short Sꢀ ꢀ ꢀO distances and
linear C–Sꢀ ꢀ ꢀO angle, are established, providing a planar
1
7
conformation of the s-trans type (Scheme 2). The s-cis
conformation, characterized by an intramolecular
NOXꢀ ꢀ ꢀS
non-bonded interaction was found to be iso-
SMe
energetic, yet it was not experimentally observed in the
neutral donor. The associated energy barrier between the
two stable planar conformations was estimated to be at
Figure 1. ORTEP view of one of the two independent molecules of (S)-
EDT-TTF–(SMe)–OX 3b (thermal ellipsoids set at 50% probability).
ꢁ
1
around 7 kcal mol
.
˚
Selected parameters: distances (A) C(3)–C(4) 1.353(8), O(1)ꢀ ꢀ ꢀS(7) 2.84;
angles (ꢁ): O(1)ꢀ ꢀ ꢀS(7)–C(15) 168.4, folding (ꢁ): S(1)ꢀ ꢀ ꢀS(2) 6.9, S(3)ꢀ ꢀ ꢀS(4)
˚ ˚
1
4.4. Crystal data: monoclinic P2 ; a = 11.1573(12) A, b = 12.9363(11) A,
1
Me
˚
˚
3
c = 13.6472(16) A, b = 101.212(13)ꢁ; cell volume V = 1932.2(3) A ; Z = 4;
N
S
O
S
Me
T = 293(2); R = 0.0464 (‘observed’ data).
1
S
S
S
S
S
S
S
S
N
S
S
S
S
O
However, in spite of the stabilization provided by these
short intramolecular contacts, the N,S auxiliary should
very likely coordinate to the iridium(I) centre in a chelating
manner, as already described with thioether–oxazoline
Me
Me
EDT-TTF-SMe-Me-OX
s-trans
EDT-TTF-SMe-Me-OX
s-cis
1
2
ligands, although no X-ray structural data on this type
of Ir complexes have been reported so far.
Scheme 2. Sꢀ ꢀ ꢀO and Sꢀ ꢀ ꢀN nonbonded interactions in EDT-TTF–SMe–
MeOX ligands.
Cationic iridium complexes of our TTF-based ligands
(Scheme 3) have been conventionally synthesized from
Therefore, the establishment of Oꢀ ꢀ ꢀS non-bonded inter-
actions within the EDT-TTF–SMe–OX ligands provides,
most likely, additional stabilization for these planar con-
formations. Thus, if the thioether–oxazolines are expected
to act as chelating N,S ligands, the associated energy of
the non-bonded interaction has to be overcome by the sta-
the dimeric precursor [Ir(COD)Cl] . One equivalent of
2
the dimer was reacted with 2.1 equiv of the selected TTF
ligand in CH Cl for 6 h. Then 1 equiv of AgPF was
2
2
6
added and, within a period of 15 min stirring, the chloride
abstraction occurred, to yield the required cationic catalyst
precursor. A filtration over Celite allowed us to remove the
bilization provided by the chelation onto the metal centre.
II
In the case of the Cu (hfac) (hfac = hexafluoro-acetyl-
AgCl salt. Alternatively, instead of AgPF , NaBArF
2
6
ꢁ
acetonate) fragment, the metal centre was only monocoor-
dinated to the NOX atom, thus still preserving the Oꢀ ꢀ ꢀS
non-bonded interaction, whereas the Co(II) centre, which
has a much more pronounced tendency towards hexacoor-
(BArF = tetrakis[3,5-bis(trifluoromethyl)-phenyl]borate)
can be used, in which case, the resulting NaCl was elimi-
nated simply by washing with water.
1
9
dination, was N,S chelated. It is worthwhile mentioning
this feature in view of the catalytic experiments planned
with such auxiliaries. Indeed, an N,S chelation onto an
iridium centre will most probably be beneficial to the selec-
tivity of the hydrogenation process. Over the course of our
present investigations, we have been able to grow single
The cationic complexes thus obtained were used without
any further purification in catalysis, since they were analyt-
1
31
ically pure according to the H and P NMR data. The
hydrogenation of the imine was performed into an auto-
clave under 30 bar of H (Scheme 4) and the results are re-
2
ported in Table 1. The solution containing the imine and
the selected iridium precatalyst in dry degassed CH Cl
i
crystals from the enantiopure EDT-TTF–SMe– PrOX
2
2
ligands 3a and 3b upon recrystallization in a THF/cyclo-
hexane mixture, and then to determine their solid state
was introduced into the autoclave. After pressurization
with dihydrogen, the reaction mixture was stirred under

C. R e´ thor e´ et al. / Tetrahedron: Asymmetry 18 (2007) 1877–1882
1879
was very active (100% conversion after several hours) and
O
O
X
Y
*
2
2
quite selective (57% ee, entry 3). In an attempt to increase
the selectivity, the temperature was decreased first to 5 ꢁC,
then to ꢁ10 ꢁC. A temperature decrease was very detrimen-
tal to the conversion, which dropped to 20% (entry 4) and
then to 13% (entry 5), respectively. Unexpectedly, the ee
dropped to 35% at ꢁ10 ꢁC versus 57% at room tempera-
ture. Conversely, a reaction temperature of 50 ꢁC did not
allow any improvement of the selectivity, although the
activity was unaltered (entry 6).
S
S
S
S
S
S
S
N
Ir
N
PF6
S
S
Ir
S
S
+
-
S
[(2)Ir(COD)] Y , X = PPh2, Y = PF6, BArF
+
[
(1)Ir(COD)] PF6-
+ -
[
(3)Ir(COD)] Y , X = SMe, Y = PF6
Scheme 3. Cationic iridium complexes.
"
IrL" cat.
A peculiar aspect in the TTF–PHOX auxiliaries series is
represented by the sense of the enantioselectivity they
induce. Indeed, with our enantiopure ligands, the absolute
configuration of the resulting amine is the same as the
one of the PHOX ligand, that is, the (R)-TTF–PHOX
affords the (R)-amine. This observation is in sharp contrast
with the results obtained in the case of other PHOX
ligands, for which opposite absolute configurations are
*
Ph
+
H2
Ph
Ph
N
CH Cl
Ph
N
2
2
3
0 bar
H
1
5 h
Scheme 4. Imine hydrogenation.
the conditions reported in Table 1. At the end of the reac-
tion, the crude mixture was analyzed by GC for conversion
determination. Then, after filtration through basic alumina
to eliminate the catalyst, the mixture was analyzed on a chi-
ral HPLC column for determination of the ee’s.
1
0
noticed generally between the ligand and the amine.
Indeed, if the iridium catalyst contains the (S)-PHOX
ligand enantiomer, the sense of the selectivity was rational-
ized by considering the hydrogen transfer to the Si face of
1
0b,c,k
the imine.
The latter is usually the anti-isomer,
The first series of experiments have been performed with
the cationic iridium complexes containing the PF6 coun-
although it is known that acyclic imines exist as mixtures
of slowly interconverting anti- and syn-isomers. This
ꢁ
23
terion. With the simple TTF–oxazolines 1, the conversion
was very disappointing (only 4%, entry 1) with also a low
ee (9%). Although one can assume that in the catalytic
intermediates the iridium(I) centre probably interacts with
the appropriate TTF inner S atom, in order to form a che-
late, this interaction is certainly very weak and does not
provide a good stabilization of the coordination sphere of
the metal during the enantiodetermining step of the cata-
lytic cycle. Indeed, it is known that TTF inner sulfur atoms
rationale is in agreement with the quadrants rule, when
taking into account the steric hindrance around the coordi-
nated metal centre, as deduced from single crystal X-ray
structures of the starting Ir complexes. Unfortunately, in
our case, we were unable to grow single crystals from the
iridium complexes. Therefore, in order to explain this dif-
ference in selectivity, we can only suggest that the steric
hindrance provided by the TTF backbone induces the
coordination of the imine with the Si face in the case of
the (R)-TTF–PHOX, thus affording the (R)-amine after
the hydrogen transfer. In addition, electronic interactions,
such as p stacking or C–Hꢀ ꢀ ꢀPh, with the imine phenyl
group might be important as well.
1
9,20
do not possess good coordination abilities,
and, more-
over, simple TTF–oxazolines are poor ligands for the
1
8,21
asymmetric allylic substitution.
Similar results were ob-
tained with TTF–SMe–oxazoline auxiliaries 3 (entry 2), de-
spite the fact that recently, oxazoline thioether ligands
proved to be effective in terms of activity for this reaction,
Next, we used iridium precatalysts containing the more
1
2
ꢁ
yet without any selectivity. Interestingly, we found that
hindered non-coordinating anion BArF in the same
the catalyst obtained from the precursor [Ir(2b)(COD)]PF6
hydrogenation conditions. Accordingly, the ee increased
Table 1.
a
b
c
Entry
Ligand or catalytic precursor
Anion
T (ꢁC)
Conv. (%)
ee (%) (Config).
i
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
1
2
3
4
5
6
7
8
9
EDT-TTF–(R)- PrOX
PF6
PF6
PF6
PF6
PF6
PF6
20
20
20
4
7
100
20
9 (S)
nd
i
EDT-TTF–SMe–(R)- PrOX
i
EDT-TTF–PPh
EDT-TTF–PPh
EDT-TTF–PPh
EDT-TTF–PPh
EDT-TTF–PPh
EDT-TTF–PPh
EDT-TTF–PPh
EDT-TTF–PPh
2
2
2
2
2
2
2
2
–(R)- PrOX
57 (R)
56 (R)
35 (R)
58 (R)
68 (R)
62 (R)
69 (R)
57 (R)
23 (R)
i
–(R)- PrOX
5
i
–(R)- PrOX
ꢁ10
13
i
–(R)- PrOX
50
100
100
32
22
100
i
ꢁ
–(R)- PrOX
BArF
BArF
BArF
BArF
20
5
i
ꢁ
ꢁ
ꢁ
–(R)- PrOX
i
–(R)- PrOX
ꢁ10
i
1
1
0
1
–(R)- PrOX
50
i
2+
ꢁ
ꢁ
d
[Ir(COD)EDT-TTF–PPh
2
– PrOX] , PF6 , SbF6
20
20 (70 )
a
b
c
Reactions were carried out by using 0.42 mmol of imine in 5 mL of distilled CH
Conversions were determined by GPC.
Enantiomeric excesses were determined by HPLC on a Chiralpak OJ column. Absolute configuration was determined by comparison with those obtained
2 2
Cl under 30 bar of hydrogen. S/Ir = 50; t = 15 h.
with (S)-PHOX ligand.
Conversion after 4 days.
d

1880
C. R e´ thor e´ et al. / Tetrahedron: Asymmetry 18 (2007) 1877–1882
up to 68% always with full conversion (entry 7). A variable
temperature study afforded the same trends as in the case
4.1. Synthesis of complexes [Ir(COD)(1b)]PF (R) and
6
[Ir(COD)(1c)]PF (S)
6
of the PF anion, namely a dramatic loss of activity at
6
low temperatures (entries 8 and 9) and basically no influ-
ence between room temperature and 50 ꢁC (entry 10).
Finally, the hydrogenation reaction was carried out with
the cationic Ir(I) complex of the oxidized ligand 2b (entry
The ligand 1b (38.4 mg, 94.5 lmol) and the dimer complex
bis(g -cycloocta-1.5-diene)-di-l-chlorodiiridium(I) [Ir(COD)-
Cl]2 (30 mg, 44.2 lmol) were placed under an inert
atmosphere, then dissolved in distilled and degassed meth-
ylene chloride (2 mL). The dark red solution was stirred for
6 h at room temperature, before addition of 1 equiv of
4
1
1), prepared upon chemical oxidation of the complex with
NOSbF . This preliminary experiment aimed at emphasiz-
6
ing the influence of the TTF oxidation state on the catalytic
process, such as it was demonstrated with ferrocene based
AgPF (23 mg, 88.4 lmol) in the dark. After 15 min of stir-
ring, filtration through dry Celite and evaporation in vacuo
6
2
4
redox active ligands. Unlike the case of the asymmetric
allylic alkylation, for which no real influence on the activity
afforded a dark brown powder (42.9 mg, 57% yield). MS
+
(MALDI-TOF) m/z: 704.55 (MꢁPF ) ; Anal. Calcd for
6
1
8
or selectivity was observed, in the present experiment a
dramatic decrease of both activity (20%) and selectivity
C H F IrNOPS : C, 31.05; H, 3.20; N, 1.64; Found: C,
2
2
27
6
6
31.85; H, 3.58; N, 1.79.
(
20% ee) were observed. Nevertheless, prolonged reaction
times allowed us to reach up to 70% yield in amine. How-
ever, it should be pointed out that, at this preliminary
stage, it is difficult to conclude whether the effect we
observed here is due to the electronic modulation provided
by the oxidized ligand or to another catalytic species gener-
ated in the reaction mixture under the reducing conditions
of the hydrogenation process. Additional investigations are
needed in order to investigate the different hypotheses.
The same procedure with ligand 1c afforded the Ir complex
(dark powder, 43.6 mg, 58% yield). Anal. Calcd for
C H F IrNOPS : C, 31.05; H, 3.20; N, 1.64. Found: C,
2
2
27
6
6
31.62; H, 3.38; N, 1.85.
4.2. Synthesis of complexes [Ir(COD)(3a)]PF (R) and
6
[Ir(COD)(3b)]PF (S)
6
i
The ligand (R)-EDT-TTF–SMe– PrOX 3a (42.8 mg,
4
9
4.5 lmol) and the dimer complex bis(g -cycloocta-1.5-
3. Conclusion
diene)-di-l-chlorodiiridium(I)
[Ir(COD)Cl]2
(30 mg,
4
4.2 lmol) were placed under an inert atmosphere, then
i
Chiral redox active monodentate EDT-TTF– Pr–oxazo-
dissolved in distilled and degassed dichloromethane
(2 mL). The dark red solution was stirred for 6 h at room
temperature, then 1 equiv of AgPF (23 mg, 88.4 lmol)
i
lines (TTF–OX) and bidentate EDT-TTF–SMe– Pr–oxaz-
i
olines
(TTF–SMe–OX)
and
EDT-TTF–PPh – Pr–
2
6
oxazolines (EDT-TTF–PHOX) have been evaluated in
the catalytic hydrogenation of N-(phenylethylidene)aniline,
while associated to cationic iridium(I) complexes. High
was added in the dark. After 15 min of stirring, filtration
through dry Celite and evaporation of solvent in vacuo
1
afforded a dark brown powder (52.1 mg, 66% yield). H
3
activities (100% conversion) and good selectivities could
NMR (CD Cl , d): 0.66 (d, J = 7.0 Hz, 3H, CH ), 0.89
2
2
3
i
3
be attained with the EDT-TTF–PPh – PrOX ligands and
(d, J = 7.0 Hz, 3H, CH ), 1.74 (m, 3H, CH (COD) and
2
3 2
ꢁ
ꢁ
PF6 (up to 58% ee) or BArF (up to 68% ee) anions. Fur-
ther studies in our groups will be aimed at the utilization of
these TTF–oxazoline based ligands in other catalytic pro-
cesses, and also at the understanding of the influence of
the TTF oxidation state on the catalytic process.
CH–(CH ) ), 2.37 (m, 2H, CH , COD), 2.40 (s, 3H,
3 2 2
SCH ), 2.46–2.82 (m, 5H, 2CH and 1 CH, COD), 3.22
3
2
(m, 1H, CH, COD), 3.31 (m, 4H, S–CH –CH –S), 4.40
2
2
(m, 1H, CH, COD), 4.58 (m, 1H, CH, COD), 4.65–4.76
0
(m, 2H, N–CH and CH
H O), 5.01 (m, 1H,
syn/i-Pr
0
31
1
CHH
OÞ; P NMR (CD Cl , d): ꢁ144.4 (h, J
=
anti=i-Pr
2
2
P–F
7
10 Hz, PF ); MS (MALDITOF) m/z: 704.50
6
+
4
. Experimental
(MꢁSMeꢁPF ) ; Anal. Calcd for C H F NOPIrS : C,
6
23 29
6
7
3
0.79; H, 3.26; N, 1.56. Found: C, 29.85; H, 3.43; N, 1.27.
All the reactions were carried out under an inert gas atmo-
sphere. Solvents were purified by standard techniques:
THF was distilled over sodium and benzophenone; aceto-
nitrile was dried over P O . The triethylamine was distilled
The same procedure with the ligand 3b afforded the Ir com-
plex (dark powder, 53.7 mg, 68% yield). Anal. Calcd for
C H F NOPIrS : C, 30.79; H, 3.26; N, 1.56. Found: C,
2
5
23 29
6
7
over KOH. Nuclear magnetic resonance spectra were
recorded on a Bruker Avance DRX 500 spectrometer operat-
30.06; H, 3.25; N, 1.31.
1
13
ing at 500.04 MHz for H, 125.75 MHz for C and
4.3. Synthesis of complexes [Ir(COD)(2a)]PF (±)ꢀ
6
[Ir(COD)(2b)]PF (R) and [Ir(COD)(2c)]PF (S)
6
3
1
2
02.39 MHz for P. Chemical shifts are expressed in parts
6
per million (ppm) downfield from the external TMS. The
following abbreviations are used: s, singlet; d, doublet; t,
i
The ligand (± )-EDT-TTF–PHOX( Pr) 2a (37 mg,
3
1
triplet; o, octuplet; m, multiplet; b, broad. P chemical
shifts are reported with positive values downfield from
external 85% H PO in D O. MALDI-TOF MS spectra
0.063 mmol) and the dimer complex [Ir(COD)Cl] (20 mg,
2
0.03 mmol) were placed under an inert atmosphere, and
then dissolved in distilled and degassed dichloromethane
(1.4 mL). The dark solution was stirred for 6 h at room
temperature, and then 1 equiv of AgPF6 (16 mg,
0.06 mmol) was added in the dark. After stirring for
15 min, filtration through dry Celite and evaporation in
3
4
2
were recorded on Bruker Biflex-IIITM apparatus,
equipped with a 337 nm N laser. Elemental analyses were
2
performed by the ‘Service d’Analyse du CNRS’ at Gif/
Yvette, France.

C. R e´ thor e´ et al. / Tetrahedron: Asymmetry 18 (2007) 1877–1882
1881
vacuo afforded a black crystalline powder (60.8 mg, 98%
nitrile (2 mL). The dark solution thus obtained was stirred
for 1 h at room temperature. The solvent was then removed
upon evaporation, and thus a black powder was obtained
(42 mg, 87 % yield). Anal. Calcd for C H F NOP S-
1
3
yield). H NMR (CD Cl , d): 0.26 (d, J = 7.0 Hz, 3H,
2
2
3
CH ), 0.92 (d, J = 7.0 Hz, 3H, CH ), 1.61 (m, 2H, CH ,
3
3
2
COD), 2.09 (m, 4H, CH–(CH ) , CH and CH, COD),
3
2
2
34 36 12
2
2
3
4
.34 (m, 1H, CH, COD), 2.43–2.55 (m, 2H, CH , COD),
bIrS : C, 32.13; H, 2.86; N, 1.10. Found: C, 31.35; H,
3.02; N, 1.75.
2
6
.29 (m, 4H, S–CH –CH –S), 3.88 (m, 1H, CH, COD),
2
2
.17 (m, 1H, N–CH), 4.22 (m, 1H, CH, COD), 4.44
0
3
2
(
t, J = J = 9.5 Hz, 1H, CH
J = 9.5 Hz, J = 3.3 Hz, 1H, CHH
H O), 4.50 (dd,
syn/i-Pr
0
4.6. General procedure for the hydrogenation of N-benz-
ylmethyl-phenylimine (Ir/substrate ratio = 2 mol %)
2
3
O), 7.31 (m, 2H,
anti=i-Pr
3
1
Ph), 7.47–7.71 (m, 4H, Ph), 8.00 (m, 4H, Ph); P NMR
1
i
(
CD Cl , d): 12.1 (s, PPh ), ꢁ144.5 (h, J
= 710 Hz,
2
2
2
P–F
[{EDT-TTF–PPh
2
– PrOX}Ir(COD)]PF
6
(8.9 mg, 8.6 lmol)
+
PF ); MS (MALDITOF) m/z: 889.72 (MꢁPF ) ; Anal.
6
6
was placed under a nitrogen atmosphere and dissolved
in freshly distilled and degassed dichloromethane (5 mL).
The imine (83 mg, 0.42 mmol) and a magnetic stirring
bar were placed in a 50 mL autoclave, which was then
purged with nitrogen. The catalyst solution was transferred
under nitrogen in the autoclave, which was then pressur-
ized (30 bars) with dihydrogen. The mixture was stirred
at the specified temperature for 15 h. Then, the autoclave
was depressurized and the solution, of which a sample
was taken in order to determine the conversion by GC,
was purified through a short silica gel column (eluant:
dichloromethane) to afford the amine as a clear yellow oil.
Calcd for C H F NOP IrS : C, 39.45; H, 3.51; N, 1.35.
3
4
36
6
2
6
Found: C, 38.62; H, 4.06; N, 1.14.
The same procedure with ligand 2b (black powder,
5
yield). [Ir(COD)(2b)]PF : Anal. Calcd for C H F NO-
P IrS : C, 39.45; H, 3.51; N, 1.35. Found: C, 38.75; H,
5.7 mg, 90% yield) and 2c (black powder, 60.9 mg, 98%
6
34 36 6
2
6
4
.05; N, 1.03. [Ir(COD)(2c)]PF6: Anal. Calcd for
C H F NOP IrS : C, 39.45; H, 3.51; N, 1.35. Found:
C, 38.73; H, 4.01; N, 1.01.
3
4
36
6
2
6
4
[
.4. Synthesis of complexes [Ir(COD)(2b)]BArF (R) and
Ir(COD)(2c)]BArF (S)
The conversion was evaluated by gas chromatography
(
GC). When the temperature rises from 120 ꢁC to 230 ꢁC
The ligand 2b (16.8 mg, 28.5 lmol) and the dimer complex
Ir(COD)Cl] (9.5 mg, 14 lmol) were placed under an inert
with a 10 ꢁC/min gradient, the retention times are
10.1 min for the amine and 10.4 min for the starting imine.
[
2
atmosphere and dissolved in 5 mL dry and degassed
dichloromethane. The dark solution was stirred for one
night at room temperature. Then, 1 equiv of NaBArF
4.7. X-ray crystallography
(
26 mg, 28 lmol) was added, followed by water (6 mL).
Data were collected on a Stoe Imaging Plate System
IPDS) operating with a Mo-Ka X-ray tube with a graphite
The two layers were separated and the aqueous one was
extracted with dichloromethane (3 · 10 mL). The organic
layers were combined and dried over MgSO . Filtration and
(
monochromator. The structures were solved (SHELXS-97)
by direct methods and refined (SHELXL-97) by full-matrix
4
removal of the solvent provided a black crystalline powder
2 25
least-square procedures on F . Hydrogen atoms were
1
(
37.2 mg, 76% yield). H NMR (CD Cl , d): 0.23 (d,
2
2
introduced at calculated positions (riding model), included
in structure factor calculations but not refined. All the hea-
vy atoms have been refined anisotropically. Crystallo-
graphic data have been deposited with the Cambridge
Crystallographic Data Center as Supplementary Publica-
tion No. CCDC 652986 (3a) and CCDC 652987 (3b)
(CIF files). Copies of these data can be obtained free of
charge on application to CCDC, 12 Union Road, Cam-
bridge CB21EZ, UK (e-mail: deposit@ccdc.cam.ac.uk).
3
3
J = 7.0 Hz, 3H, CH ), 0.90 (d, J = 7.0 Hz, 3H, CH ),
3
3
1
.72 (m, 2H, CH , COD), 1.95–2.16 (m, 3H, CH (COD)
2
2
and CH–(CH ) ), 2.43–2.60 (m, 4H, CH , COD), 2.85
(
3
2
2
m, 1H, CH, COD), 3.29 (m, 4H, S–CH –CH –S), 3.38
2 2
(
m, 1H, CH, COD), 4.13 (m, 1H, N–CH), 4.39 (t,
3
2
2
0
J = J = 9.3 Hz,
1H,
CH
H O),
4.51
(dd,
syn/i-Pr
0
3
J = 9.3 Hz, J = 3.0 Hz, 1H, CHH
O), 5.01 (m, 1H,
anti=i-Pr
CH, COD), 5.16 (m, 1H, CH, COD), 7.25 (m, 2H, Ph),
7
3
1
.47–7.77 (m, 16H, Ph, BArF), 7.98 (m, 4H, Ph);
P
NMR (CD Cl , d): 12.9 (s, PPh ); MS (MALDITOF)
2
2
2
+
m/z: 889.82 (MꢁBArF) ; Anal. Calcd for C H F BNO-
6
6
48 24
Acknowledgements
PIrS : C, 45.21; H, 2.76; N, 0.80. Found: C, 44.55; H, 2.91;
6
N, 0.44.
Financial support from the CNRS, Minist e` re de
l’Education et de la Recherche (grants to C.R. and F.R.)
is gratefully acknowledged.
The same procedure with ligand 2c (black powder, 55.7 mg,
9
0% yield). Anal. Calcd for C H F BNOPIrS : C, 45.21;
66 48 24 6
H, 2.76; N, 0.80. Found: C, 44.65; H, 2.88; N, 0.56.
+
.5. Synthesis of the oxidized complexes [Ir(COD)(2a–c) ]-
Å
References
4
PF ꢀSbF
6
6
1
. (a) Handbook of Homogeneous Hydrogenation; de Vries, J. G.,
Elsevier, C. J., Eds.; Wiley-VCH: Weinheim, 2006; (b)
Kwong, F. Y.; Lam, W. H.; Chan, A. S. C. Adv. Org. Synth.
2005, 1, 261; (c) Tang, W.; Zhang, X. Chem. Rev. 2003, 103,
3029; (d) Blaser, H.-U.; Malan, C.; Pugin, B.; Spindler, F.;
Steiner, H.; Studer, M. Adv. Synth. Catal. 2003, 345, 103; (e)
The series of complexes [Ir(COD)(2a–c)]PF6 (30 mg,
2
2
9 lmol) and the oxidizing agent NOSbF6 (7.7 mg,
9 lmol) were weighed in a glove box, placed into a
Schlenk tube, and dissolved in dry and degassed aceto-

1882
C. R e´ thor e´ et al. / Tetrahedron: Asymmetry 18 (2007) 1877–1882
Ohkuma, T.; Kitamura, M.; Noyori, R In Catalytic Asym-
9. (a) Blaser, H.-U.; Spindler, F. Top. Catal. 1998, 4, 275; (b)
Werbitzky, O. Chem. Eng. News 1998, 19, 64.
metric Synthesis, 2nd ed.; Ojima, I., Ed.; Wiley-VCH: New
York, NY, 2000; (f) Comprehensive Asymmetric Catalysis;
Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer:
Berlin, 1999; Vol. I; (g) Noyori, R. Asymmetric Catalysis in
Organic Synthesis; Wiley-VCH: NewYork, 1994, 16.
. (a) Chi, Y.; Tang, X. Modern Rhodium-catalyzed Organic
Reactions 2005, 1–31; (b) Xie, J.-H.; Wang, L.-X.; Fu, Y.;
Zhu, S.-F.; Fan, B.-M.; Duan, H.-F.; Zhou, Q.-L. J. Am.
Chem. Soc. 2003, 125, 4404.
. (a) Zanotti-Gerosa, A.; Herns, W.; Groarke, M.; Hancock, F.
Platinum Met. Rev. 2005, 49, 158; (b) Kuroki, Y.; Asada, D.;
Sakamaki, Y.; Iseki, K. Tetrahedron Lett. 2000, 41, 4603; (c)
Ratovelomanana-Vidal, V.; Gen eˆ t, J.-P. J. Organomet. Chem.
10. (a) Li, X.; Li, Q.; Wu, X.; Gao, Y.; Xu, D.; Kong, L.
Tetrahedron: Asymmetry 2007, 18, 629; (b) Zhu, S.-F.; Xie, J.-
B.; Zhang, Y.-Z.; Li, S.; Zhou, Q.-L. J. Am. Chem. Soc. 2006,
128, 12886; (c) Trifonova, A.; Diesen, J. S.; Andersson, P. G.
Chem. Eur. J. 2006, 12, 2318; (d) Trifonova, A.; Diesen, J. S.;
Chapman, C. J.; Andersson, P. G. Org. Lett. 2004, 6, 3825;
(e) Ezhova, M. B.; Patrick, B. O.; James, B. R.; Waller, F. J.;
Ford, M. E. J. Mol. Catal. A 2004, 7111; (f) Cozzi, P. G.;
Menges, F.; Kaiser, S. Synlett 2003, 833; (g) Martorell, A.;
Claver, C.; Fernandez, E. Inorg. Chem. Commun. 2000, 3,
132; (h) Kainz, S.; Brinkmann, A.; Leitner, W.; Pfaltz, A. J.
Am. Chem. Soc. 1999, 121, 6421; (i) Hilgraf, R.; Pfaltz, A.
Synlett 1999, 1814; (j) Lightfoot, A.; Schnider, P.; Pfaltz, A.
Angew. Chem. Int. Ed. 1998, 37, 2897; (k) Schnider, P.; Koch,
G.; Pr e´ t oˆ t, R.; Wang, G.; Bohnen, F. M.; Kr u¨ ger, C.; Pfaltz,
A. Chem. Eur. J. 1997, 3, 887.
2
3
1
998, 567, 163.
4
5
. (a) Bunlaksananusorn, Y.; Polborn, K.; Knochel, P. Angew.
Chem., Int. Ed. 2003, 42, 3941; (b) Drury, W. J., III;
Zimmermann, N.; Keenan, M.; Hayashi, M.; Kaiser, S.;
Goddard, R.; Pfaltz, A. Angew. Chem., Int. Ed 2004, 43, 70;
11. (a) Blankenstein, J.; Pfaltz, A. Angew. Chem., Int. Ed. 2001,
40, 4445; (b) Menges, F.; Pfaltz, A. Adv. Synth. Catal. 2002,
344, 40.
12. Guiu, E.; Claver, C.; Castillon, S. J. Organomet. Chem. 2004,
689, 1911.
(
c) Troutman, D. H.; Appella, D. H.; Buchwald, S. L. J. Am.
Chem. Soc. 1999, 121, 4916; (d) Bell, S.; W u¨ stenberg, B.;
Kaiser, S.; Menges, F.; Netscher, T.; Pfaltz, A. Science 2006,
3
11, 642.
. (a) Dervisi, A.; Carcedo, C.; Ooi, L. Adv. Synth. Catal. 2006,
48, 175; (b) Spindler, F.; Blaser, H.-U. Transition Metals for
13. Blanc, C.; Agbossou-Niedercorn, F.; Nowogrocki, G. Tetra-
hedron: Asymmetry 2004, 15, 2159.
3
Organic Synthesis, 2nd ed.; Wiley-VCH: Weinheim, 2004;
Vol. 2, p 113; (c) Pfaltz, A.; Blankenstein, J.; Hilgraf, R.;
H o¨ rman, E.; McIntyre, S.; Menges, F.; Sch o¨ nleber, M.;
Smidt, S. P.; W u¨ stenberg, B.; Zimmermann, N. Adv. Synth.
Catal. 2003, 345, 33; (d) Tang, W.; Wang, W.; Zhang, X.
Angew. Chem., Int. Ed. 2003, 42, 943; (e) Xiao, D.; Xu, G.;
Gilbertson, R. G. Tetrahedron Lett. 2003, 44, 953; (f) Zhang,
X. Angew. Chem., Int. Ed. 2001, 40, 3425; (g) Blackmond, D.
G.; Lightfoot, A.; Pfaltz, A.; Rosner, T.; Schnider, P.;
Zimmermann, N. Chirality 2000, 12, 442; (h) Tararov, V. I.;
Kadyrov, R.; Riermeier, T. H.; Holz, J.; B o¨ rner, A. Tetra-
hedron: Asymmetry 1999, 10, 4009.
14. R e´ thor e´ , C.; Fourmigu e´ , M.; Avarvari, N. Tetrahedron 2005,
61, 10935–10942.
15. R e´ thor e´ , C.; Avarvari, N.; Canadell, E.; Auban-Senzier, P.;
Fourmigu e´ , M. J. Am. Chem. Soc. 2005, 127, 5748–5749.
16. R e´ thor e´ , C.; Fourmigu e´ , M.; Avarvari, N. Chem. Commun.
2004, 1384–1385.
17. R e´ thor e´ , C.; Madalan, A. M.; Fourmigu e´ , M.; Canadell, E.;
Lopes, E. B.; Almeida, M.; Cl e´ rac, R.; Avarvari, N. New. J.
Chem. 2007, 31, 1468–1483.
18. R e´ thor e´ , C.; Suisse, I.; Agbossou-Niedercorn, F.; Guillam o´ n,
E.; Llusar, R.; Fourmigu e´ , M.; Avarvari, N. Tetrahedron
2006, 62, 11942–11947.
6
. Willoughby, C. A.; Buchwald, S. L. J. Am. Chem. Soc. 1994,
19. Madalan, A. M.; R e´ thor e´ , C.; Avarvari, N. Inorg. Chim. Acta
2007, 360, 233–240.
1
16, 8952.
7
. (a) Vargas, S.; Rubio, M.; Su a´ rez, A.; del Rio, D.; Alvarez,
E.; Pizzano, A. Organometallics 2006, 25, 961; (b) Imamoto,
T.; Iwadate, N.; Yoshida, K. Org. Lett. 2006, 8, 2289; (c)
Moessner, C.; Bolm, C. Angew. Chem., Int. Ed. 2005, 44,
20. (a) Kuroda-Sowa, T.; Hirata, M.; Munakata, M.; Maekawa,
M. Chem. Lett. 1998, 499; (b) Matsubayashi, G.; Yokoyama,
K.; Tanaka, T. J. Chem. Soc., Dalton Trans. 1988, 3059.
21. Chesney, A.; Bryce, M. R. Tetrahedron: Asymmetry 1996, 7,
3247.
7
564; (d) Dorta, R.; Broggini, D.; Stoop, R.; R u¨ egger, H.;
Spindler, F.; Togni, A. Chem. Eur. J. 2004, 10, 267; (e) Jiang,
X.-B.; Minnaard, A. J.; Feringa, B. H.; Duchateau, A. L. L.;
Guiu, E.; Munoz, B.; Castillon, S.; Claver, C. Adv. Synth.
Catal. 2003, 345, 169; (f) Andrien, J. G. O.; Boogers, J. A. F.;
de Vries, J. G. Org. Lett. 2003, 5, 1503; (g) Cahill, J. O.;
Lightfoot, A. P.; Goddard, R.; Rust, J.; Guiry, P. J.
Tetrahedron: Asymmetry 1998, 9, 4307.
. (a) Blaser, H.-U.; Brieden, W.; Pugin, B.; Spindler, F.; Studer,
M.; Togni, A. Top. Catal. 2002, 19, 3; (b) Blaser, H.-U.; Buer,
H. P.; Ha u¨ sel, R.; Jalett, H. P.; Spindler, F. J. Organomet.
Chem. 2001, 621, 34; (c) Togni, A.; Breutel, C.; Schnyder, A.;
Spindler, F.; Landert, H.; Tijani, A. J. Am. Chem. Soc. 1994,
22. The reactions carried out with the ligands of (S) configuration
lead to the enantiomeric product with the same results, while
the use of the racemic ligands provides the racemic product
with the same activity.
23. Smith, J. K.; Bergbreiter, D. E.; Newcomb, M. J. Am. Chem.
Soc. 1983, 105, 4396.
24. (a) Lorkovic, I. M.; Duff, R. R., Jr.; Wrighton, M. S. J. Am.
Chem. Soc. 1995, 117, 3617; (b) Gregson, C. K. A.; Gibson,
V. C.; Long, N. J.; Marshall, E. L.; Oxford, P. J.; White, A. J.
P. J. Am. Chem. Soc. 2006, 128, 7410.
25. Sheldrick, G. M. Programs for the Refinement of Crystal
Structures; University of G o¨ ttingen: G o¨ ttingen (Germany),
1996.
8
1
16, 4062.