Asymmetric hydrogenation of aromatic ketones with new P-chirogenic monophosphine ligands

Article abstract of DOI:10.1016/j.tetasy.2007.05.026

Novel P-chirogenic anisylphenyl-HMOP derivatives have been synthesised from (R)-2,2′-bis-(trifluoromethanesulfonyloxy)1,1′-binaphthyl. Preliminary results concerning the asymmetric hydrogenation of acetophenone and 3,5-bis(trifluoromethyl)acetophenone with Ru(II)-HMOP complexes in combination with various diamines was also tackled.

Full text of DOI:10.1016/j.tetasy.2007.05.026

Tetrahedron: Asymmetry 18 (2007) 1224–1232
Asymmetric hydrogenation of aromatic ketones with new
P-chirogenic monophosphine ligands
*
*
´
Mohamad Jahjah, Rabih Jahjah, Stephane Pellet-Rostaing and Marc Lemaire
ICBMS, Institut de chimie et BiochimieMole´culaire et Supramole´culaire, UMR-CNRS 5246, Universite´ de Lyon, Universite´ Claude
Bernard Lyon 1, CPE Lyon, 43 Bd du 11 Novembre 1918, 69622 Villeurbanne Cedex, France
Received 17 April 2007; accepted 23 May 2007
Abstract—Novel P-chirogenic anisylphenyl-HMOP derivatives have been synthesised from (R)-2,20-bis-(trifluoromethanesulfonyl-
oxy)1,10-binaphthyl. Preliminary results concerning the asymmetric hydrogenation of acetophenone and 3,5-bis(trifluoromethyl)aceto-
phenone with Ru(II)-HMOP complexes in combination with various diamines was also tackled.
ꢀ 2007 Elsevier Ltd. All rights reserved.
1. Introduction
phosphine with the (R)-2-((trifluoromethanesulfonyl)oxy)-
20-methoxy-1,10-binaphthyl (Scheme 1) and the isolation
of the enantiomerically pure P-chirogenic phosphines via
their borane adducts.
The catalytic enantioselective hydrogenation of C@O
bonds is of a great interest for the synthesis of a large
amount of enantiomerically pure compounds and consider-
able progress has been achieved in this area.1–3 Typically,
rhodium(I) and ruthenium(II) complexes and, most often,
diphosphine-based chiral ligands, play a central role as che-
lating agents for transition metals in homogeneous cataly-
sis,4,5 because of their intrinsic electronic properties and
steric variability. Among them, atropoisomeric diaryl-core
diphosphanes such as BINAP are continuously attracting
interest in view of their exceptional ability to induce asym-
metry in transition metal-catalysed reactions.6 Earlier in
this area, P-stereogenic monophosphine ligands,7 in which
the stereogenic centre is the phosphorus atom itself, have
been developed as attractive ligands. More recently, exam-
ples have proven that P-stereogenic diphosphines can be
more efficient than ligands with chirality located in the
ligand backbone.8–10 Combining the chiral 1,10-binaphthyl
skeleton of the Hayashi’s MeO–MOP ligand11 with the P-
stereogenic centre of the Knowles’s diPAMP,12 Gilheany
very recently described13 the synthesis of anisylphenylMOP
hybrid ligands potentially relevant to the catalytic asym-
metric addition of boronic acids to aldehydes. Although
MOP derivatives are usually prepared from (R)- or (S)-
2,20-bis(trifluoromethanesulfonyloxy)1,10-binaphthyl,14,15
the authors proposed the direct coupling of the secondary
Herein, we report how (R,R)-H- and (R,S)-HMOP deriva-
tives (2-(arylphenylphosphino)-1,10-binaphthyls) 1 can be
efficiently prepared from the starting (R)-2,20-bis(tri-
fluoromethanesulfonyloxy)1,10-binaphthyl following the
same strategy that is already applied to the preparation
of various substituted BINAP16 (Fig. 1). Based on the
well-known diamine/Ru/BINAP system developed by
Noyori,17–20 we also describe our preliminary results on
the asymmetric hydrogenation of aromatic ketones.
2. Results and discussion
2.1. Synthesis of phosphines boranes
Chiral phosphine borane complexes were synthesised start-
ing from the dichlorophenylphosphine following the syn-
thetic route already described in the literature.21,22
Dichlorophenylphosphine reacted with the previously pre-
pared Grignard reagent at ꢀ78 ꢁC in THF. Treatment with
LiAlH4 followed by the addition of BMS in the anhydrous
THF gave the desired phosphine borane (Scheme 1).
Thus, t-butylphenylphosphine borane 2, o-anisylphenyl-
phosphine borane 3 and 2,4-dimethoxyphenylphosphine
borane 4 were obtained, respectively, from the starting
*
Corresponding authors. Tel.: +33 (0) 4 72 43 14 07; fax: +33 (0) 4 72 43
14 08 (S.P.R.); e-mail: pellet@univ-lyon1.fr
0957-4166/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.05.026

M. Jahjah et al. / Tetrahedron: Asymmetry 18 (2007) 1224–1232
1225
BH3
R = t-butyl
P
H
2
68%
1) RMgBr, -78 °C
2) LiAlH4, -78 °C - 0 °C
3) BMS, 0 °C - r.t.
BH3
P
R = o-anisyl
PCl2
3
38%
THF
H
MeO
BH3
P
R = 2,4-dimethoxyphenyl
33%
OMe
4
H
MeO
Scheme 1.
1)
OTf
1) RMgBr
2) LiAlH4
3) BMS
OTf
BH3
*
P
PCl2
P
H
R
NiCl2dppe, DABCO
DMF
THF
R
2) H2O2, CH2Cl2
3) reduction
1
Figure 1.
t-butylmagnesium chloride, o-anisylmagnesium bromide
and 2,4-dimethoxyphenylmagnesium bromide in 68%,
38% and 33% yields. The low isolated yields could be
explained by the formation of disubstituted by-products,
due to the reactivity of the chlorophenyl(aryl or alkyl)phos-
phine intermediates. In fact, when methyl-, isopropyl-,
p-anisyl-, 3,4,5-trimethoxyphenyl- or cyclohexylmagnesium
bromides were reacted with the dichlorophenylphosphine,
only the disubstituted phenylphosphine borane complexes
were obtained. As a result, we assumed that in all the cases,
the monosubstituted intermediates were more reactive than
the starting dichlorophenylphosphine and that only the
more sterically hindered Grignard reagents (t-Bu, o-anisyl
and o,p-methoxybenzene) allowed us to prepare the reac-
tive phosphine borane complexes.
On the other hand, when o-anisylphenylphosphine borane
3 was engaged in the coupling reaction, a diastereoisomeric
mixture of two monophosphines was isolated in 70% yield,
which were unfortunately inseparable. 31P NMR confirmed
the presence of two diastereoisomeric monophosphines
with two phosphorus resonance signals located at
ꢀ22.6 ppm and ꢀ23.0 ppm, whereas four resonance signals
were kept if the diphosphine structures had been obtained,
giving three diastereoisomers. With no resonance signal,
19F NMR confirmed that the second triflate group was
cleaved during the reaction. Oxidation of the mixture was
then achieved with H2O2 in dichloromethane affording
pure monophosphine oxides 6 and 7, which were isolated
by column chromatography in 31% and 33% yields, respec-
tively. Subsequent cleavage of the methyl group with BBr3
in CH2Cl2 at 0 ꢁC led to hydroxyl derivatives 8 and 9 in
quantitative yield.
2.2. Coupling of the phosphine borane complexes
The coupling reaction of the 2,4-dimethoxyphenylphos-
phine borane complex 4 with (R)-5 followed by the oxida-
tion of the corresponding monophosphines intermediates
afforded a mixture of monophosphine oxides 10 and 11
in 45% and 41% yields, respectively, after purification on
column chromatography (Scheme 3).
The coupling reaction of the (R)-2,20-bis(trifluoro-
methanesulfonyloxy)1,10-binaphthyl (R)-5 with the phos-
phine borane complexes 2–4 was carried out according to
the method of Cai23 in the presence of NiCl2/dppe and
DABCO in DMF at 125 ꢁC.24,25
The first aim of our work was focused on the direct
synthesis of P-chirogenic diphosphines type BINAP
(Scheme 2). Surprisingly, the coupling reaction of
tert-butylphenylphosphine borane 2 with (R)-5 failed
and only the reduction product 1,10-binaphthyl was
recovered.
2.3. Determination of the enantiomeric excess of the
monophosphines oxides 6 and 7
In order to determine the enantiomeric excess of the iso-
lated monophosphine oxides 6 and 7, a mixture of diastereo-

1226
M. Jahjah et al. / Tetrahedron: Asymmetry 18 (2007) 1224–1232
P
NiCl2dppe, DABCO
DMF, 2, 125 °C, 24 h
H
H
t-Bu
t-Bu
+
P
100%
0%
OTf
OTf
BBr3, CH2Cl2
r.t.
1)NiCl2dppe, DABCO
P
O
(R)-5
P
DMF, 3, 125 °C, 24 h
O
100%
HO
MeO
2) H2O2, CH2Cl2
(R,S) and (R,R)
8 and 9
(R,S) and (R,R)
6 and 7
31%
33%
Scheme 2.
1)NiCl2dppe, DABCO
P
OMe
DMF,4, 125 °C, 24 h
P
OMe
+
OTf
OTf
O
O
MeO
MeO
2) H2O2, CH2Cl2
(R,S)
(R,R)
(45%)
(41%)
(R)-5
10 and 11
Scheme 3.
isomers (R,R), (R,S), (R,R) and (S,R) were synthesised in
60% yield, starting from the racemic 2,20-bis(trifluoro-
methanesulfonyloxy)1,10-binaphthyl (Scheme 4). Purifica-
tion by column chromatography afforded two mixtures of
enantiomers which were analysed and compared with dia-
stereoisomers 6 and 7 by chiral HPLC (DAICEL Chiral
pack AD column). Analysis of the obtained chromato-
grams ensured that the enantiomeric excess of 6 and 7
was close to 99%.
2.4. Reduction of the phosphine oxides
Reduction of the phosphine oxides was ineffective with tra-
27
ditional reducing agents, such as HSiCl3,26 LiAlH4 and
PhSiH3.28 Full reduction to the phosphine occurred but
significant epimerisation was observed, from 31P NMR
spectra of the reduction products, which varied depending
on the experimental conditions.
When 6 and 7 were treated with trichlorosilane and N,N-
dimethylaniline in toluene at 45 ꢁC, the corresponding pure
HMOP 12 and 13 were obtained in 80% and 82% yields
with a retention of the optical integrity of the compounds
(Scheme 5).
In order to assign their configuration, we focused our
efforts on the structure elucidation of 6 and 7 by X-ray crys-
tallographic study. However recrystallisation of both pure
compounds failed.
1)NiCl2dppe, DABCO
DMF, 3, 125 °C, 24 h
OTf
(R,R)
(S,S)
P
(R,S)
O
OTf
(S,R)
2) H2O2, CH2Cl2
MeO
60%
( )
Scheme 4.

M. Jahjah et al. / Tetrahedron: Asymmetry 18 (2007) 1224–1232
1227
HSiCl3
N,N-dimethylaniline
P
P
O
Toluene, 45 °C
80% and 82%
MeO
MeO
(R,S) and (R,R)
6 and 7
(R,S) and (R,R)
12 and 13
Scheme 5.
Table 1. Asymmetric hydrogenation of acetophenone with catalysts
containing 13
Nevertheless when the reaction was carried out on enantio-
merically pure diastereoisomers 10 and 11, epimerisation
occurred (15%). Epimerisation was also observed for the
reduction of diastereoisomers 8 and 9 (30%). Reduction
of 8–11 was then performed according to the method devel-
oped by Imamoto29 (LiAlH4, MeOTf), which allowed the
reduction of several chiral phosphine oxides with an inver-
sion of their configuration. With total conversions and ex-
pected inversion of configuration, the level of epimerisation
nevertheless varied from 10% to 20%, which limited the use
of these ligands in the continuation of our work in asym-
metric catalysis.
Entry Metallic precursors Solvent Base
Conv. (%) ee (%)
1b
2b
3a
4b
5c
[Ru(COD)Cl2]x
[Ru(p-cymene)Cl2]2 i-PrOH t-BuOK
[Ru(C6H6)Cl2]2
[Ru(C6H6)Cl2]2
[Ru(C6H6)Cl2]2
i-PrOH t-BuOK
60
76
23
3 (S)
9 (S)
0
13 (S)
9 (S)
MeOH t-BuOK
i-PrOH t-BuOK 100
i-PrOH t-BuOK 100
[S] = 0.3 M and S/M/t-BuOK/L* = 100/1/10/1; 30 bar of H2; 50 ꢁC; 18 h.
a [M]+13+MeOH, 1 h at 50 ꢁC, then addition of acetophenone.
b [M]+13+i-PrOH, 7–16 h at rt, then addition of t-BuOK and
acetophenone.
c [M]+13+Toluene, 1 h at rt, then evaporation of toluene and addition of
i-PrOH and t-BuOK and acetophenone.
2.5. Hydrogenation of aromatic ketones
The asymmetric hydrogenation of acetophenone was firstly
carried out under hydrogen pressure (30 bars) at room tem-
perature in the presence of the chiral catalyst prepared
in situ. Catalysts were prepared by the addition of the chi-
ral ligand to the metal precursor in an appropriate solvent.
The base was added to the reaction mixture just before the
addition of acetophenone (Scheme 6).
temperature (Table 1, entries 2 and 4). It should be noted
that complex [Ru(C6H6)Cl2]2/13 in methanol led to a low
activity and did not allow any enantioselectivity. There-
fore, the [Ru(C6H6)Cl2]2 dimer gave the best result with
monophosphine 13 and has been used as catalytic precur-
sor in the continuation of our study.
Since the role of a co-ligand, such as a diamine, was crucial
in these experimental conditions of hydrogenation,17–20
(1R,2R)-DPEN (DPEN: 1,2-diphenylethylenediamine)
was first combined with [Ru(C6H6)Cl2]2/13 catalytic sys-
tem. The complex [Ru(C6H6)Cl2]2 (1% M), the chiral
monophosphine 13 (1% M) and diamine (1% M) were
mixed in i-PrOH. After 16 h of stirring, t-BuOK (5–10%
M) and acetophenone were added successively before being
set under a hydrogen pressure. An increase of the ee to 33%
was then obtained with a quantitative conversion (Table 2)
H2 (30 bars)
OH
O
MLnXm (1%), L* (1,1%),
i-PrOH, t-BuOK (10%)
r.t.
Scheme 6.
Monophosphine (R)-2((R or S)-o-anisylphenylphosphino)-
1,10-binaphthyl 13 was evaluated in the asymmetric hydro-
genation of acetophenone with several ruthenium precur-
sors (Table 1). Hydrogenation reaction with the
ruthenium species was carried out under experimental con-
ditions already described by Noyori et al. (t-BuOK, i-
PrOH). When the reaction mixture was stirred for 24 h
without H2, no reaction occurred.
Table 2. Monophosphines 12 and 13 in asymmetric hydrogenation of
acetophenone with [Ru(C6H6)Cl2]2 and co-ligand
General structure
L* Diamine
Conv. (%) ee (%)
12
13
90
100
0
33 (S)
When [Ru(COD)Cl2]2 and [Ru(p-cymene)Cl2]2 were used
with 13 under H2 (30 bars), conversions were not quantita-
tive and enantiomeric excesses were low (entries 1 and 2).
Only [Ru(C6H6)Cl2]2/13 catalytic system in isopropanol
gave a quantitative conversion of acetophenone (Table 1,
entries 4 and 5) but low enantioselectivities were also ob-
served. A small improvement in enantioselectivity was ob-
tained when the catalyst was prepared in the isopropanol
starting from [Ru(C6H6)Cl2]2 and 13 for 7–16 h at room
P
H2N
NH2
NH2
H3CO
12
13
95
100
4 (S)
11 (R)
H2N
[S] = 0.3 M and S/M/t-BuOK/L*/diamine = 100/1/10/1.1/1; i-PrOH, 16 h
at rt then addition of t-BuOK and acetophenone; 30 bar of H2.

1228
M. Jahjah et al. / Tetrahedron: Asymmetry 18 (2007) 1224–1232
in favour of the (S)-phenylethanol. With (1S,2S)-DIA-
PEN, the ee was lower (11%) in favour of the (R)-phenyl-
ethanol. Thus, the asymmetric induction seemed to be
predominantly governed by the nature of the DPEN.
Moreover, whatever the configuration of the DPEN, the
reduction was not quantitative with diastereoisomer 12
and no enantioselectivity was observed.
enantioselectivity were noticed when more than 1 equiv
of diamine was introduced in the reaction mixture. We
assumed that the active catalyst was a 1/1/1 metal/ligand/
diamine system.
In order to evaluate the reliability of the catalytic system
with other aromatic ketones, the asymmetric hydrogena-
tion of 3,5-bis(trifluoromethyl)acetophenone was carried
out under optimised conditions applied to the reduction
of acetophenone (Scheme 7).
In order to improve the enantioselectivity of the hydroge-
nation with 13, several chiral diamines were also tested as
co-ligands (Table 3). Nevertheless, none of them caused
an increase in the ee which did not exceed 33% (Table 3,
entries 1 and 5) with the (1R,2R)-diphenylethylenediamine
and the (1R,2R)-N,N0-dimethyl-1,2,diphenyl-1,2-ethanedi-
amine. In all cases, the (S)-enantiomer of the phenyletha-
nol was mainly obtained when (R,R)- or (R)-diamines
were engaged in the reaction (Table 3, entries 1, 3, 5 and
7). Contrary, (1R)-phenylethanol was obtained with
(S,S)- or (S)-diamines (Tables 3, entries 2, 4, 6 and 8).
OH
H2 (30 bar)
[Ru(C6H6)Cl2]2 (1%)
13 (1.1%), diamine (1%)
O
F3C
F3C
i-PrOH, t-BuOK (10%)
CF3
CF3
r.t.
Scheme 7.
Since the (R)-1-[3,5-bis-(trifluoromethyl)phenyl]ethanol
was used as a key intermediate in the synthesis of the tachy-
kinin NK1 receptor antagonist L-754030, a potent anti-
depressant,30,31 several options for the asymmetric reduc-
tion of the 3,5-bis(trifluoromethyl)acetophenone were con-
sidered. To the best of our knowledge, the Noyori’s
diamine/Ru/BINAP combination has not been evaluated
for the particular hydrogenation of this aromatic ketone.
On the other hand, the enantioselective hydrogenation of
the 3,5-bis(trifluoromethyl)acetophenone with Ru(II) com-
plexes composed of achiral monophosphine ligands in
combination with the enantiopure DPEN was studied in
n-PrOH with t-BuOK and gave an ee of 90%.32
Table 3. Asymmetric hydrogenation of acetophenone with [Ru(C6H6)-
Cl2]2/13 and diamine as co-ligands
Entry Co-ligand
Conv. (%) ee (%)
1
2
3
4
5
(1R,2R)-Diphenylethylenediamine
100
100
100
100
33 (S)
11 (R)
6 (S)
2 (R)
33 (S)
(1S,2S)-Diphenylethylenediamine
(1R,2R)-Diaminocyclohexane
(1S,2S)-Diaminocyclohexane
(1R,2R)-N,N0-Dimethyl-1,2,diphenyl- 100
1,2-ethanediamine
6
(1S,2S)-N,N0-Dimethyl-1,2,diphenyl- 100
1,2-ethanediamine
20 (R)
7
8
(R)-1,10Binaphthyl-2,20-diamine
(S)-1,10Binaphthyl-2,20-diamine
100
100
13 (S)
2 (R)
[S] = 0.3 M and S/M/t-BuOK/L*/diamine = 100/1/10/1.1/1; i-PrOH, agi-
tation 12 h at rt then addition of t-BuOK and acetophenone; 30 bar of H2.
The hydrogenation of the 3,5-bis(trifluoromethyl)acetoph-
enone was carried out by using the BINAP or monophos-
phine 13 and [Ru(C6H6)Cl2]2 with various diamines
(Table 5).
In order to evaluate the real contribution of the P-chiro-
genic ligand towards the asymmetric induction of the
hydrogenation of acetophenone, achiral diamines were also
studied as a co-ligand (Table 4).
Table 5. Asymmetric hydrogenation of m-bisfluoromethylacetophenone
with [Ru(C6H6)Cl2]2/(13 or BINAP) and diamine as co-ligands
Entry Ligand
Co-ligand
Conv. (%) ee (%)
Quantitative conversions were reached and ee’s propor-
tionally increased with an increase in the number of carbon
atoms between the two nitrogen atoms (Table 4, entries 1–
3). The ee reached its maximum (61%) in the presence of
1,4-diaminobutane (Table 4, entry 3). With longer alkyl
chains (Table 4, entries 4 and 5), the ee’s, as well as the con-
versions rate, decreased. We have also studied the effect of
the Ru/13/diamine ratio and no changes concerning the
1
2
3
4
(R)-BINAP (1R,2R)-DIAPEN
(R)-BINAP 1,3-Diaminopropane
4
8
91
0
0
13
13
1,3-Diaminopropane
1,4-Diaminobutane
53 (S)
63 (S)
100
[S] = 0.3 M and S/M/t-BuOK/L*/diamine = 100/1/10/1.1/1; i-PrOH, 18 h
at rt then addition of t-BuOK and acetophenones; 30 bar of H2.
Reduction of 3,5-bis(trifluoromethyl)acetophenone in the
presence of the BINAP proved inefficient with DPEN
and 1,3-diaminopropane (entries 1 and 2). On the other
hand, with monophosphine 13, good conversion rates were
obtained. Moreover, enantioselectivity reached 53% in the
presence of 1,3-diaminopropane as a co-ligand and 63% in
the presence of the 1,4-diaminobutane.
Table 4. Asymmetric hydrogenation of acetophenone with [Ru(C6H6)-
Cl2]2/13 and diamine as co-ligands
Entry
Co-ligand
Conv. (%)
ee (%)
1
2
3
4
5
6
1,2-Diaminoethane
1,3-Diaminopropane
1,4-Diaminobutane
1,5-Diaminopentane
1,6-Diaminohexane
N,N0-Dimethylethylenediamine
100
100
100
63
53
100
10 (S)
46 (S)
61 (S)
6 (S)
0
3. Conclusion
0
[S] = 0.3 M and S/M/t-BuOK/L*/diamine = 100/1/10/1.1/1; i-PrOH, 12 h
at rt then addition of t-BuOK and acetophenone; 30 bar of H2.
In conclusion, despite the growing interest in chiral mono-
phosphine ligands, only a few examples of atropoisomeric

M. Jahjah et al. / Tetrahedron: Asymmetry 18 (2007) 1224–1232
1229
chiral monophosphine have been reported in the literature.
We have devised a new approach for the synthesis of new
P-chirogenic atropoisomeric monophosphines combining
nickel-catalysed coupling reactions of easily available
binaphthyl building-blocks with various complexes of
phosphine borane.
in 20 mL of dry THF at ꢀ78 ꢁC was added a 1.30 M solu-
tion of t-butylmagnesium chloride in THF (12.75 mL,
16.5 mmol) for 1 h under Ar. LiAlH4 (0.63 g, 16.5 mmol)
was then added portionwise at ꢀ78 ꢁC and stirring was
continued at room temperature for 1 h. The mixture was
then cooled at 0 ꢁC and borane-methyl sulphide complex
(2 M in THF, 8.25 mL, 20 mmol) added. After stirring
for an additional 1 h, the reaction mixture was carefully
poured into a 1 M aqueous solution of HCl (50 mL), water
(50 mL) and ethyl acetate (25 mL). The organic layer was
separated and the aqueous layer extracted with ethyl ace-
tate (3 · 20 mL). The combined extracts were washed with
brine (3 · 20 mL) and dried over MgSO4, filtered and con-
centrated under reduced pressure. The crude product was
purified by flash chromatography (SiO2, cyclohexane/ethyl
To the best of our knowledge, this study is the first report on
the use of monophosphine chiral inductors for aromatic ke-
tones hydrogenation. In the case of ruthenium species, we
have developed a new catalytic and enantioselective system
for the asymmetric hydrogenation of acetophenone: the
best result (100% conversion, 61% ee) was obtained with
(R)-2((R or S)-o-anisylphenylphosphino)-1,10-binaphthyl
13 and 1,4-diaminobutane coordinated to [Ru(C6H6)Cl2]2.
On the other hand for the asymmetric hydrogenation of
3,5-bis(trifluoromethyl)acetophenone: the best result
(100% conversion, 63% ee) was obtained with (R)-2((R or
S)-o-anisylphenylphosphino)-1,10-binaphthyl 13 and 1,4-
diaminobutane. This is the first result obtained for the
asymmetric hydrogenation of aromatic ketones with a P-
chirogenic monophosphorus ruthenium catalyst. We have
noticed a synergetic co-ligand effect between the monophos-
phine and some achiral diamines, increasing both the activ-
ity and enantioselectivity of the ruthenium catalysts.
1
acetate 95/5) affording 2 (2 g, 68%) as a colourless oil. H
NMR (300 MHz, CDCl3): d = 1.18 (d, J = 14.0 Hz, 9H,
1
3
3 · CH3), 5.05 (dq, JH–P = 360 Hz, JH–H = 7 Hz, 1H,
HP), 7.40–7.55 (m, 3ArH); 7.60–7.70 (m, 2ArH); 31P
NMR (81 MHz, CDCl3): d = 31.5 (m); Elemental Anal.
Calcd for C10H18BP (180.12): C, 66.71; H, 10.08. Found:
C, 66.83; H, 10.08.
4.2.1.2. o-Anisylphenylphosphine-borane 3. This was
obtained by the same procedure from o-anisylmagnesium
bromide and purified by flash chromatography (SiO2, hep-
tane/dichloromethane 7/3) as a white solid (38%). 1H
NMR (300 MHz, CDCl3): d = 0.65–1.3 (m, 3H, BH3),
4. Experimental
4.1. General
1
3
3.84 (s, 3H, OCH3), 6.52 (dq, JH–P = 395.2 Hz, JH–H
=
6.85 Hz, 1H, HP), 6.92 (dd, J = 8.28, 3.39 Hz, 1ArH),
7.06 (td, J = 7.41, 1.11 Hz, 1ArH), 7.35–7.51 (m, 4ArH),
7.61–7.72 (m, 2ArH), 7.77 (td, J = 6.30, 1.89 Hz, 1ArH);
31P NMR (81 MHz, CDCl3): d = ꢀ15.2 (m); Elemental
Anal. Calcd for C13H16BOP (230.10): C, 67.87; H, 7.01.
Found: C, 67.93; H, 7.00.
All the organic and organometallic reagents used were of
pure commercial products. The solvents from Carlo Erba,
anhydrous THF were prepared in the laboratory. Enantio-
merically pure BINOL was obtained from ACROS,
dichlorophenylphosphine from Aldrich. All manipulations
of organometallic compounds were carried out under an
argon atmosphere. The metallic precursors were purchased
from STREM.
4.2.1.3.
2,4-Dimethoxyphenylphenylphosphine-borane
4. This was obtained by the same procedure from 2,4-
methoxyphenylmagnesium bromide and purified by flash
chromatography (SiO2, heptane/dichloromethane 7.5/2.5)
as a white solid (814 mg, 33%). 1H NMR (300 MHz,
CDCl3): d = 0.63–1.35 (m, 3H, BH3), 3.81 (s, 3H, OCH3),
Melting points (mp), were determined with a Ko¨fler Bench
type WME (HeIZBANK) and are uncorrected. Elemental
analyses (C, H, P) were obtained from the Service Central
d’Analyse of the CNRS (Solaize). High resolution mass
spectra: HR LSIMS (Liquid Secondary Ionisation Mass
Spectrometry: Thioglycerol), HR CIMS (Isobutan) and
1
3
3.85 (s, 3H, OCH3), 6.45 (dq, JH–P = 394.68 Hz, JH–H
=
6.78 Hz, 1H, HP), 6.48 (t, J = 5.25 Hz, 1ArH), 6.62 (d,
J = 8.49 Hz, 1ArH), 7.37–7.43 (m, 3ArH), 7.61–7.69 (m,
1ArH), 7.72 (d, J = 8.49, 1ArH), 7.78 (d, J = 8.67,
1ArH); 31P NMR (81 MHz, CDCl3): d = ꢀ 16.8 (m); Ele-
mental Anal. Calcd for C14H18BO2P (260.11): C, 64.65;
H, 6.98. Found: C, 64.97; H, 7.05.
HR EIMS were carried out on a Finnegan MAT 95xL
25
by the UCBL Centre de Spectroscopie de Masse. ½aꢁD
was determined with a Perkin–Elmer 241 polarimeter
(l = 1 dm; 25 ꢁC; concentration c in g/mL). H, 13C and
1
31P NMR spectra were recorded on a Bruker AC-200
(200.13 MHz for 1H, 50.32 MHz for 13C) or AC-300 FT
(300.13 MHz for 1H, 75.46 MHz for 13C, 81 MHz for
31P) spectrometer; d values are given in ppm and J in hertz.
The ee values and conversion were determined by chiral
GC (Cyclodex b column, 30 m).
4.2.2. Phosphine oxides 6, 7, 10 and 11
4.2.2.1. (R)-2(R or S)[(-o-Anisylphenyl)phosphinyl]-1,10-
binaphthyl 6 and 7. To a solution of [1,2-bis(diph-
enylphosphino)-ethane]dichloronickel (291 mg, 0.55 mmol)
in dry DMF (28 mL), (R)-2,20-bis(trifluoromethanesulfo-
nyloxy)-1,10binaphthyl (R)-5 (3 g, 5.50 mmol), 1,4-diaza-
bicyclo[2,2,2]octane (3.70 g, 33.10 mmol) and (o-
4.2. Synthesis
anisylphenylphosphine)
borane-complex
3
(2.39 g,
11.0 mmol) were added at room temperature under Ar.
The mixture was stirred at room temperature for 30 min
and then at 125 ꢁC for 24 h. DMF was evaporated under
reduced pressure, then dichloromethane (50 mL) and
4.2.1. Phosphine borane complexes
4.2.1.1. t-Butylphenylphosphine-borane 2. To a stirred
mixture of dichlorophenylphosphine (2.25 mL, 16.5 mmol)

1230
M. Jahjah et al. / Tetrahedron: Asymmetry 18 (2007) 1224–1232
H2O2 10% (7 mL) were added at 0 ꢁC. The mixture was
stirred at room temperature for 8 h, then poured into water
(10 mL). The organic layer was washed with a saturated
solution of sodium bisulfite (1 mL) and extracted with
dichloromethane (3 · 20 mL). Solvents were evaporated
under reduced pressure and the dark yellow residue was
purified by flash chromatography on silica gel (SiO2, cyclo-
hexane/ethyl acetate 6/4) to afford pure 6 as a yellow solid
and 7 as a yellow solid (0.85 g and 0.89 g, 31% and 33%,
respectively) with a global yield of 65%.
(OCH3), 55.5 (OCH3), 97.2, 105.4, 125.1, 125.2, 125.3,
126.7, 127.1, 127.5, 127.6, 127.7, 128.0, 128.0, 128.1,
128.2, 128.5, 128.7, 128.9, 131.2, 131.3, 132.5, 132.7,
132.9, 133.1, 133.2, 133.7, 133.8, 134.4, 134.5, 134.6,
134.7, 134.8, 134.9, 143.4, 143.5, 160.2, 162.8, 163.6; 31P
NMR (81 MHz, CDCl3): d = +27.0 (s); MS (ESI): m/z:
515.2 [M+H]+; Elemental Anal. Calcd for C34H27O3P
(515.2): C, 79.36; H, 5.29; P, 6.02. Found: C, 79.00; H,
6.17; P, 5.37; mp 199 ꢁC; Rf = 0.52 (cyclohexane/ethyl ace-
25
tate 4/6); ½aꢁD ¼ ꢀ30:25 (c 0.79, CH2Cl2).
1
1
Compound 6: H NMR (300 MHz, CDCl3): d = 3.41 (s,
Compound 11: H NMR (300 MHz, CDCl3): d = 3.60 (s,
3H, OCH3), 6.05 (dd, J = 8.31, 5.88 Hz, 1ArH), 6.50 (td,
J = 7.53, 1.14 Hz, 1ArH), 6.83–6.93 (m, 2ArH), 7.05 (td,
J = 8.28, 1.32 Hz, 1ArH), 7.20 (td, J = 3.21, 1.89 Hz,
1ArH), 7.23–7.28 (m, 4ArH), 7.33–7.39 (m, 4ArH), 7.42
(t, J = 6.78 Hz, 2ArH), 7.47–7.54 (m, 2ArH), 7.88–7.92
(m, 4ArH); 13C NMR (75 MHz, CDCl3): d = 54.4
(OCH3); 109,2; 109.3; 119.1; 120.4; 120.5; 125.1; 125.2;
125.3; 126.8; 127.0; 127.6; 127.8; 128.1; 128.1; 128.2;
128.4; 128.5; 129.0; 131.4; 131.4; 132.3; 132.4; 132.6;
132.8; 132.9; 133.1; 133.4; 133.5; 133.6; 133.8; 134.6;
134.7; 134.8; 143.6; 158.7; 31P NMR (81 MHz, CDCl3):
d = 27.1 (s); MS (ESI): m/z: 485.2 [M+H]+; Elemental
Anal. Calcd for C33H24O2P (484.16): C, 81.80; H, 5.2; P,
3H, OCH3), 3.81 (s, 3H, OCH3), 6.26 (dd, J = 4.71,
2.07 Hz, 1ArH), 5.42 (td, J = 8.46, 1.68 Hz, 1ArH), 6.84
(td, J = 7.74, 3.03 Hz, 2ArH), 6.99 (td, J = 6.03, 3.21 Hz,
1ArH), 7.03 (d, J = 7.71 Hz, 1ArH), 7.15 (td, J = 6.78,
3 Hz, 2ArH), 7.23 (td, J = 6.6, 1.14 Hz, 1ArH), 7.33 (td,
J = 8.07, 1.14 Hz, 2ArH), 7.39 (dd, J = 12.46, 1.32 Hz,
1ArH), 7.42 (d, J = 12.6 Hz, 1ArH), 7.51 (d, J = 6.6 Hz,
2ArH), 7.53–7.68 (m, 3ArH), 7.77–7.84 (m, 1ArH), 7.92–
7.97 (m, 2ArH); 13C NMR (75 MHz, CDCl3): d = 55.3
(OCH3), 55.7 (OCH3), 98.6, 98.7, 105.4, 105.5, 125.0,
125.5, 125.7, 126.8, 127.0, 127.2, 127.4, 127.6, 127.7,
127.8, 128.1, 128.2, 128.8, 128.9, 129.0, 130.2, 130.3,
130.4, 131.1, 131.2, 133.1, 133.2, 133.6, 133.8, 134.8,
134.8, 135.0, 135.1, 136.2, 136.3, 143.4, 161.6; 31P NMR
(81 MHz, CDCl3): d = +28.0 (s); MS (ESI): m/z: 515.2
[M+H]+; Elemental Anal. Calcd for C34H27O3P (515.2):
C, 79.36; H, 5.29; P, 6.02. Found: C, 79.85; H, 5.99; P,
6.39. Found: C, 82.40; H, 5.65; P, 6.5; mp 190 ꢁC;
25
Rf = 0.45 (cyclohexane/ethyl acetate 5/5); ½aꢁD ¼ ꢀ33:3 (c
0.75, CH2Cl2).
1
Compound 7: H NMR (300 MHz, CDCl3): d = 3.63 (s,
6.02; mp 171 ꢁC; Rf = 0.16 (cyclohexane/ethyl acetate, 4/
25
3H, OCH3), 6.76 (dd, J = 8.07, 5.46 Hz, 1ArH), 6.84 (td,
J = 7.71, 3 Hz, 2ArH), 6.94 (td, J = 7.53, 1.14 Hz,
1ArH), 7.00 (td, J = 7.14, 1.32 Hz, 1ArH), 7.09 (d,
J = 8.1, 1ArH), 7.22–7.41 (m, 8ArH), 7.51–7.70 (m,
2ArH), 7.71–7.79 (m, 2ArH), 7.91–7.96 (m, 4ArH); 13C
NMR (75 MHz, CDCl3): d = 55.33 (OCH3); 111.0; 121.2;
121.3; 125.0; 125.5; 125.8; 126.9; 127.0; 127.2; 127.4;
127.6; 127.8; 127.9; 128.1; 128.2; 128.7; 128.9; 128.9;
130.3; 130.4; 130.6; 131.6; 131.2; 133.1; 133.3; 133.6;
133.7; 133.8; 134.7; 134.8; 134.9, 135; 135.1; 143.4; 143.5;
160.1; 31P NMR (81 MHz, CDCl3): d = 28.1 (s); MS
(ESI): m/z: 485.2 [M+H]+; Elemental Anal. Calcd for
C33H24O2P (484.16): C, 81.80; H, 5.2; P, 6.39. Found: C,
6); ½aꢁD ¼ ꢀ38:0 (c 0.79, CH2Cl2).
4.2.3. Phosphine oxides 8 and 9
4.2.3.1. (R)-2(R or S)[(-2-Hydroxyphenyl)phenylphosphin-
yl]-1,10-binaphthyl 8.
A
solution of
6
(200 mg,
0.41 mmol) in dry dichloromethane (4 mL) was cooled at
0 ꢁC. A 1 M solution of BBr3 in dichloromethane
(1.2 mL, 1.2 mmol) was added and the reaction mixture
stirred at 0 ꢁC for 1 h, then at room temperature for
24 h. The solution was cooled to 5 ꢁC and methanol
(3 mL) was carefully added. After removal of the organic
solvents, the residue was dissolved in dichloromethane
(1 mL) and the solution was passed through a short column
of silica gel. The filtrate was concentrated to give 8
(195 mg, 100%) as a grey solid.
79.70; H, 6.51; P, 5.86; mp 103–105 ꢁC; Rf = 0.46 (cyclo-
25
hexane/ethyl acetate 5/5); ½aꢁD ¼ ꢀ63:1 (c 0.75, CH2Cl2).
4.2.2.2. (R)-2(R or S)[(-2,4-dimethoxyphenyl)phenylphos-
phinyl]-1,10-binaphthyl 10 and 11. These were obtained by
the same procedure from 4 (1.28 g, 5.20 mmol) and purified
by flash chromatography (SiO2, cyclohexane/ethyl acetate
5/5) affording 10 (0.6 g, 45%) and 11 (0.54 g, 41%) as yel-
1H NMR (300 MHz, CDCl3): d = 6.10 (td, J = 7.14,
2.07 Hz, 1ArH), 6.40 (dd, J = 7.92, 4.89 Hz, 1ArH),
6.78–6.83 (m, 2ArH), 7.01–7.09 (m, 2ArH), 7.24 (t,
J = 7.14 Hz, 1ArH), 7.32–7.36 (m, 2ArH), 7.38–7.52 (m,
6ArH), 7.68–7.81 (m, 3ArH), 7.85–7.93 (m, 4ArH), 7.42
(s, 1H, OH); 13C NMR (75 MHz, CDCl3): d = 110,4;
111.8; 117.7; 117.8; 118.8; 119.0; 125.4; 125.9; 126.0;
127.2; 127.5; 128.2; 128.3; 128.4; 128.5; 128.7; 128.8;
128.9; 129.0; 129.1; 129.2; 130.4; 130.5; 132.1; 132.2;
132.3; 132.4; 132.8; 132.9; 132.9; 133.3; 133.6; 133.8;
134.0; 134.6; 134.7; 135.2; 135.3; 146.0; 146.1; 162.4; 31P
NMR (81 MHz, CDCl3): d = +39.9 (s); MS (ESI): m/z:
471.2 [M+H]+; Elemental Anal. Calcd for C32H23O2P
1
low solids with a global yield of 86%. Compound 10: H
NMR (300 MHz, CDCl3): d = 3.30 (s, 3H, OCH3), 3.53
(s, 3H, OCH3), 5.52 (dd, J = 4.89, 2.07 Hz, 1ArH), 5.91
(td, J = 8.67, 1.86 Hz, 1ArH), 6.79 (d, J = 8.28 Hz,
1ArH), 6.97 (td, J = 6.96, 1.32 Hz, 1ArH), 7.02 (d,
J = 4.71 Hz, 1ArH), 7.03–7.05 (m, 1ArH), 7.11 (dd,
J = 7.71, 1.11 Hz, 1ArH), 7.12–7.21 (m, 2ArH), 7.24 (dd,
J = 6.96, 3.0 Hz, 1ArH), 7.28 (dd, J = 8.10, 5.28 Hz,
1ArH), 7.35–7.43 (m, 1ArH), 7.53 (td J = 8.1, 6.0 Hz,
2ArH), 7.57–7.67 (m, 2ArH), 7.78–7.82 (m, 4ArH), 7.93
(s, 1ArH); 13C NMR (75 MHz, CDCl3): d = 54.4
(471.2): C, 81.69; H, 4.93; P, 6.58. Found: C, 81.65; H,
25
5.12; P, 6.48; mp 197 ꢁC; ½aꢁD ¼ ꢀ19:6 (c 0.72, CH2Cl2).

M. Jahjah et al. / Tetrahedron: Asymmetry 18 (2007) 1224–1232
1231
4.2.3.2. (R)-2(R or S)[(-2-Hydroxyphenyl)phenylphosphin-
yl]-1,10-binaphthyl 9. This was obtained by the same pro-
cedure from 7 (200 mg, 0.41 mmol) as a grey solid (193 mg,
100%).
(OCH3); 110,5; 121.3; 125.5; 125.8; 126.1; 126.6; 126.8;
126.9; 127.0; 127.6; 127.6; 128.1; 128.2; 128.3; 128.4;
128.5; 128.9; 129.0; 130.3; 130.8; 133.3; 133.4; 133.6;
133.7; 133.8; 133.9; 134.2; 135.4; 137.5; 137.7; 137.8;
161.4; 31P NMR (81 MHz, CDCl3): d = ꢀ22.6 (s); MS
(ESI): m/z: 468 [M+H]+; Elemental Anal. Calcd for
1H NMR (300 MHz, CDCl3): d = 6.64 (td, J = 7.74, 4 Hz,
1H, Harom.), 6.78–6.84 (m, 3ArH), 6.91–6.95 (m, 3ArH),
7.04 (d, J = 7.71 Hz, 1ArH), 7.09 (d, J = 6.39 Hz, 1ArH),
7.22–7.32 (m, 5ArH), 7.46 (t, J = 7.14 Hz, 1ArH), 7.53–
7.59 (m, 2ArH), 7.63 (d, J = 9.06 Hz, 1ArH), 7.87 (td,
J = 8.49, 2.25 Hz, 2ArH), 11.12 (s, 1H, OH); 13C NMR
(75 MHz, CDCl3): d = 111.7; 118.9; 119.0; 119.1; 119.2;
125.0; 125.8; 126.1; 127.2; 127.4; 127.7; 127.9; 128.2;
128.3; 128.7; 128.9; 129.1; 129.3; 130.3; 130.5; 130.5;
130.6; 130.9; 131.0; 131.7; 131.9; 132.0; 133.1; 133.8;
133.9; 134.1; 134.2; 134.5; 134.6; 135.2; 135.3; 145.6;
164.4; 31P NMR (81 MHz, CDCl3): d = +40.2 (s); MS
(ESI): m/z: 471.2 [M+H]+; Elemental Anal. Calcd for
C33H25OP (468.16): C, 84.60; H, 5.38; P, 6.61. Found: C,
25
83.61; H, 5.95; P, 5.61; mp 100–102 ꢁC; ½aꢁD ¼ þ96:3 (c
0.54, CH2Cl2).
4.3. General procedures for catalytic hydrogenation
4.3.1. General procedure for hydrogenation of acetophenone
with the [Ru(C6H6)Cl2]2/L* catalysts. Method 1: In a
Schlenk tube, [Ru(C6H6)Cl2]2 (2 mg, 8 lmol) and the
selected ligand (8.80 lmol) were mixed in 1 mL of toluene
under Ar at room temperature. After 1 h of stirring, the
solvent was evaporated and 1 mL of isopropanol was
added. Then, t-BuOK (9 mg, 80 lmol) and acetophenone
(93 lL, 0.8 mmol) were introduced and the resulting solu-
tion stirred under hydrogen pressure (30 bars) in a stain-
less-steel reactor (previously degased three times with
argon and twice with hydrogen) for 7–16 h at room
temperature.
C32H23O2P (471.2): C, 81.69; H, 4.93; P, 6.58. Found: C,
25
80.76; H, 6.06; P, 6.24; mp 144–145 ꢁC; ½aꢁD ¼ ꢀ35:5 (c
0.49, CH2Cl2).
4.2.4. HMOP 12 and 13
4.2.4.1. (R)-2(R or S)[(-o-Anisyl)phenylphosphino]-1,10-
binaphthyl 12. A mixture of phosphine oxide 6 (290 mg,
0.60 mmol), N,N-dimethylaniline (0.76 mL, 6 mmol) and
trichlorosilane (0.61 mL, 6 mmol) in dry toluene (7 mL)
was warmed at 45 ꢁC for 24 h under vigorous stirring.
The mixture was cooled at 5 ꢁC, and a 1 M degassed aque-
ous solution of NaOH (3 mL) was added carefully. The
mixture was stirred at 40 ꢁC until the organic and aqueous
layers became clear. Ethyl acetate (10 mL) was then added
and the organic layer was separated. The aqueous layer
was extracted with ethyl acetate (3 · 10 mL) and the organ-
ic layers were washed with water, dried over MgSO4, fil-
tered and concentrated under reduced pressure. The
crude product was purified by short flash chromatography
(SiO2, cyclohexane/ethyl acetate 95/5) affording 12
(217 mg, 80%) as a grey solid. 1H NMR (300 MHz,
CDCl3): d = 3.51 (s, 3H, OCH3), 6.68 (m, 2ArH), 6.77
(td, J = 7.53, 0.75 Hz, 1ArH), 6.9 (dd, J = 8.49, 1.11 Hz,
1ArH), 7.11–7.32 (m, 12ArH), 7.4 (td, J = 6.96, 1.32 Hz,
2ArH), 7.79 (d, J = 8.49 Hz, 1ArH), 7.87 (td, J = 8.07,
2.82 Hz, 3ArH); 13C NMR (75 MHz, CDCl3): d = 55.6
(OCH3), 110.4, 125.2, 126.0, 126.1, 126.6, 126.7, 127.1,
127.3, 127.4, 127.5, 128.0, 128.2, 128.4, 128.6, 128.6,
128.7, 128.8, 129.3, 129.4, 129.8, 129.9, 130.1, 133.3,
133.7, 133.8, 133.9, 134.7, 135.0, 135.4, 137.2, 137.6,
137.7, 137.8, 144.5, 144.9, 161.3; 31P NMR (81 MHz,
CDCl3): d = ꢀ22.9 (s); MS (ESI): m/z: 468.16 [M+H]+;
Elemental Anal. Calcd for C33H25OP (468.16): C, 84.60;
Method 2: In a Schlenk tube, [Ru(C6H6)Cl2]2 (2 mg,
8 lmol) and the desired ligand (8.80 lmol) were mixed in
1 mL of isopropanol under argon atmosphere at room tem-
perature. After 7–12 h of stirring, t-BuOK (9 mg, 80 lmol)
and acetophenone (93 lL, 0.8 mmol) were introduced and
the resulting solution stirred under hydrogen pressure
(30 bars) in a stainless-steel reactor (previously degassed
three times with argon and twice with hydrogen) for 7–
16 h at room temperature.
4.3.2. General procedure for hydrogenation of acetophenone
with the [Ru(C6H6)Cl2]2/L*/diamine system. In a Schlenk
tube, [Ru(C6H6)Cl2]2 (2 mg, 8 lmol), the desired ligand
(8.80 lmol) and the desired amine (8 lmol) were mixed in
1 mL of isopropanol under Ar at room temperature. After
7–12 h under stirring, t-BuOK (9 mg, 80 lmol) and ace-
tophenone (93 lL, 0.8 mmol) were introduced and the
resulting solution was stirred under a hydrogen pressure
(30 bars) in a stainless-steel reactor (previously degased
three times with argon and twice with hydrogen) for 7–
16 h, at room temperature.
H, 5.38; P, 6.61. Found: C, 85.04; H, 5.93; P, 6.29; mp
186 ꢁC; ½aꢁD ¼ þ152 (c 0.5, CH2Cl2).
4.3.3. Procedure for hydrogenation of m-bisfluoromethylace-
tophenone with the system [Ru(C6H6)Cl2]2/L*/diamine. In
a Schlenk tube, [Ru(C6H6)Cl2]2 (2 mg, 8 lmol), the desired
ligand (8.80 lmol) and the desired amine (8.80 lmol) were
mixed in 1 mL of isopropanol. After 7–12 h stirring under
Ar at room temperature, t-BuOK (9 mg, 80 lmol) and m-
bisfluoromethylacetophenone (144 lL, 0.8 mmol) were
introduced and the resulting solution stirred under a
hydrogen pressure (30 bars) in a stainless-steel reactor (pre-
viously degased three times with argon and twice with
hydrogen) for 7–16 h, at room temperature.
25
4.2.4.2. (R)-2(R or S)[(-o-anisyl)phenylphosphino]-1,10-
binaphthyl 13. This was obtained by the same procedure
from 7 (390 mg, 0.80 mmol) affording 13 (300 mg, 80%)
1
as a yellow solid. H NMR (300 MHz, CDCl3): d = 3.50
(s, 3H, OCH3), 6.62–6.69 (m, 2ArH), 6.72–6.79 (m,
2ArH), 6.95–7.12 (m, 12ArH), 7.35 (dd, J = 14.49,
0.93 Hz, 1ArH), 7.37 (d, J = 15.24 Hz, 1ArH), 7.71–7.79
(m, 4ArH); 13C NMR (75 MHz, CDCl3): d = 55.9

1232
M. Jahjah et al. / Tetrahedron: Asymmetry 18 (2007) 1224–1232
4.4. GC conditions
Substrate
Conditions
Retention time
Acetophenone
Cyclodex b
60 ꢁC (5 min)–1 ꢁC/min–150 ꢁC (1 min)
Cyclodex b
Starting material: 22.99 min
Enantiomers: 30.52; 33.42 min
Starting material: 8.82 min
Enantiomers: 31.03; 31.86 min
m-Bisfluoromethyl acetophenone
60 ꢁC (1 min)–5 ꢁC/min–150 ꢁC (1 min)
13. Higham, L. J.; Clarke, E. F.; Muller-Bunz, H.; Gilheany, D.
¨
4.5. HPLC conditions for the phosphine oxide separation
G. J. Organomet. Chem. 2005, 690, 211.
14. Uozumi, Y.; Tanahashi, A.; Lee, S.-Y.; Hayashi, T. J. Org.
Chem. 1993, 58, 1945.
15. Uozumi, Y.; Suzuki, N.; Ogiwara, A.; Hayashi, T. Tetra-
hedron 1994, 50, 4293.
Chiral packꢂ AD DAICEL column, heptane/isopropanol
(75/25), wavelength: 254 nm.
Phosphine oxide: 6, retention time = 18.5 min (99%).
Phosphine oxide: 7, retention time = 19.5 min (99%).
Phosphine oxide: (R,R) and (R,S), retention time = 18.5
min and 27.5 min.
´
16. Alame, M.; Jahjah, M.; Pellet-Rostaing, S.; Lemaire, M.;
Meille, V.; De Bellefon, C. J. Mol. Catal. A 2007, 271, 18.
17. Ohkuma, T.; Ooka, H.; Hashiguchi, S.; Ikariya, T.; Noyori,
R. J. Am. Chem. Soc. 1995, 117, 2675.
18. Ohkuma, T.; Koizumi, M.; Muniz, K.; Hilt, G.; Kabuto, C.;
Noyori, R. J. Am. Chem. Soc. 2002, 124, 6508.
19. Ohkuma, T.; Doucet, H.; Pham, T.; Mikami, K.; Korenaga,
T.; Terada, M.; Noyori, R. J. Am. Chem. Soc. 1998, 120,
1086.
Phosphine oxide: (R,S) and (S,R), retention time = 19.5
min and 28.8 min.
References
20. Noyori, R.; Ohkuma, T. Angew. Chem., Int. Ed. 2001, 40, 40–
73.
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