New 5,5′-disubstituted BINAP derivatives: Syntheses and pressure and electronic effects in Rh asymmetric hydrogenation

Article abstract of DOI:10.1016/j.molcata.2006.12.019

A library of 5,5′-disubstituted BINAP derivatives were synthesized in good yield from optically pure BINAP and evaluated for the Rh-catalyzed homogeneous asymmetric hydrogenation of (α)-acylaminoacrylate ester, with ee of up to 77% being obtained with the phenyl derivative. The enantiomeric excess variation was followed according to the groups introduced in the 5,5′-position of BINAP and for a range of pressure from 5 to 30 bar.

Full text of DOI:10.1016/j.molcata.2006.12.019

Journal of Molecular Catalysis A: Chemical 268 (2007) 205–212
New 5,5ꢀ-disubstituted BINAP derivatives: Syntheses and pressure
and electronic effects in Rh asymmetric hydrogenation
M. Alamea,b, M. Jahjahb, M. Berthodb, M. Lemaireb,∗, V. Meillea, C. de Bellefona,∗∗
a Laboratoire de Ge´nie des Proce´de´s Catalytiques, UMR 2214, CNRS-CPE Lyon, 69616 Villeurbanne, France
b Laboratoire de Catalyse et Synthe`se Organique, UCB-Lyon 1, UMR 5181, 69622 Villeurbanne, France
Received 8 December 2006; accepted 11 December 2006
Available online 17 December 2006
Abstract
A library of 5,5ꢀ-disubstituted BINAP derivatives were synthesized in good yield from optically pure BINAP and evaluated for the Rh-catalyzed
homogeneous asymmetric hydrogenation of (␣)-acylaminoacrylate ester, with ee of up to 77% being obtained with the phenyl derivative. The
enantiomeric excess variation was followed according to the groups introduced in the 5,5ꢀ-position of BINAP and for a range of pressure from 5
to 30 bar.
© 2007 Published by Elsevier B.V.
Keywords: Asymmetric catalysis; Rhodium; Hydrogenation; Ligand effect
Chiral diphosphines have been known for more than 30
years [1,2], to be the most efficient type of ligands for the
asymmetric hydrogenation of C C and C O bonds, one of
the most important application of enantioselective catalysis [3].
The first developments by Knowles and Sabacky [4], Horner
et al. [5], and Kagan and coworkers [6] were rapidly followed
by the first successful commercial application of the Rh-
catalyzed hydrogenation of prochiral enamides in the Monsanto
l-DOPA process [7] and the preparation of pharmaceuticals,
agrochemicals, fragrances, and flavours [8]. In 1980, Noy-
ori and coworkers published the synthesis of BINAP [9,10]
(2,2ꢀ-bis(diphenylphosphino)-1,1ꢀ-binaphthyl), which has fur-
ther open the field of application of asymmetric hydrogenation.
Since then, the mechanism of the reaction [11] has been elu-
cidated, thousands of chiral ligands and their transition-metal
complexes have been reported [12]. Many of them, closely
related to the BINAP itself, are highly effective in the asym-
metric formation of C H, C C, C O, and C N bonds and
for transition-metal-catalyzed asymmetric synthesis in general
[13–15].
The research undertaken to date in asymmetric hydrogena-
tion relates almost exclusively to the development of new
chiral inductors to improve the selectivity of the reactions. The
key/hole concept generally used to adapt the chiral catalyst to
the prochiral substrate is however, often not operating properly.
On the contrary, many examples demonstrate the importance
of the operating conditions, such as the hydrogen pressure, on
the ee during enantioselective catalytic hydrogenations [16a].
Kinetic factors rather than thermodynamic account for such
observations, as demonstrated from the determination of the
reaction mechanism [17]. This study pointed that a small and
achiral molecule like hydrogen, can indeed exert a very strong
influence on measured ee. With regard to the asymmetrical
reductions of “enamide” type substrates by molecular hydrogen,
it is noteworthy that most of hydrogen pressure effects lead to
a decrease of the enantioselectivity. The situation is even more
complex since it is the dissolved hydrogen concentration and
not the pressure which is responsible for ee variations. The
reactor, being in charge of gas–liquid mixing, is also involved
somehow [16,18]. The situation is complex but rather clear: the
pathway to further understand the structure/enantioselectivity
relationship, that would ultimately leads to more general
predictive tools, must go through the decoupling of possible
pressure and conversion effects on ee while proceeding with a
systematic approach of intrinsic (molecular) effects. Obviously,
because many tests are being performed, such an approach
∗
∗∗
Corresponding author.
Corresponding author. Tel.: +33 472 43 17 54; fax: +33 472 43 16 73.
E-mail addresses: marc.lemaire@univ-lyon1.fr (M. Lemaire),
Claude.debellefon@lgpc.cpe.fr (C. de Bellefon).
1381-1169/$ – see front matter © 2007 Published by Elsevier B.V.
doi:10.1016/j.molcata.2006.12.019

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M. Alame et al. / Journal of Molecular Catalysis A: Chemical 268 (2007) 205–212
needs specific tools able to handle small quantities of expensive
chiral inductors (BINAP ≈ 80,000 D kg−1) [16] within a broad
range of operating conditions [19,20].
were regioselective, with only a trace of monobrominated by-
products. The dibrominated phosphines were both obtained in
80% isolated yield [24]. In the literature, the only way to func-
tionalize the 5,5ꢀ-position is nitration [25] or sulfonation [26].
Our method required a strong Lewis acid. Phosphine oxides are
Lewis bases [27] and are complexed during electronic substitu-
tion in presence of Lewis acid. Although the 4,4ꢀ-positions, close
to the phosphine oxide, were the most reactive, the presence of a
Lewis acid deactivate this position by complexing the phosphine
oxide; Br2 (activated by the presence of Fe) would brominate the
less deactivated 5,5ꢀ-position. To our knowledge, this method is
the first report, which leads to a dibrominated BINAP at the
5,5ꢀ-positions [28]. In order to study electronic effect in the
Rh-catalyzed homogeneous asymmetric hydrogenation of (␣)-
acylaminoacrylate ester we were interested in the synthesis of
new 5,5ꢀ-disubstituted BINAP derivatives by this method.
Our synthesis began from readily available BINAP (1), which
was treated with H2O2 in dichloromethane to give BINAPO
(2) and the treatment of (2) with bromine and iron at 80 ◦C in
1,2-dichloroethane give 5,5ꢀ-dibromoBINAPO (3) (Scheme 1).
The 5,5ꢀ-disubstituted BINAP derivatives were synthesized
startingfrom(3)bytwodifferentapproaches(Scheme2). Firstly,
compound (4) was synthesized from (3) in excellent yields by
reduction with a mixture of PhSiH3 and HSiCl3 at 130 ◦C.
Then, compounds (5) and (6) were obtained in very good yield
(91–96%) by lithiation of (4) with n-butyl lithium followed by
In order to extend the scope of our first studies, a library of
5,5ꢀ-disubstituted BINAP derivatives have been synthesised and
a significant number of catalytic systems of the type Rh/BINAP-
derivatives (seven catalytic systems) with various electronic and
steric properties, all featuring the same ligand backbone, have
been screened for the asymmetric hydrogenations of three pro-
chiral(acylamino)acrylic esters within a range of pressure from
5 to 30 bar.
1. Results and discussion
1.1. Synthesis
Most of the BINAP derivatives were usually prepared from
BINOL or protected BINOL with a phosphination reaction at
the end of the synthesis [21]. Lemaire and coworkers [22]
described a new strategy to obtain BINAP derivatives directly
from BINAP itself. Firstly, optically pure (R)-BINAP was trans-
formed (Scheme 1) into its corresponding dioxide 2 followed
by a regioselective bromination. The 4,4ꢀ-positions were bromi-
nated in the presence of pyridine [23] according to Kockritz
and coworkers while the 5,5ꢀ-positions were brominated in
the presence of iron as catalyst. In both cases, brominations
Scheme 1. Synthesis of 5,5ꢀ-dibromoBINAPO.
Scheme 2. Synthesis of 5,5ꢀ-(diphenyl, dimethyl, diacides)BINAP.

M. Alame et al. / Journal of Molecular Catalysis A: Chemical 268 (2007) 205–212
207
Scheme 3. Asymmetric hydrogenation of pro-chiral acyl(amino)acrylic ester with (R)-5,5ꢀ-substitued BINAP derivatives.
treatment with the desired electrophile. In the second approach,
(8) was synthesized from (3) by halogen metathesis, Suzuki
coupling, or Pd-catalyzed phosphination reaction followed by
reduction with a mixture of PhSiH3 and HSiCl3 at 130 ◦C. All
these new compounds were fully characterized.
catalysts for which both the activity and enantioselectivity are
promoted with hydrogen concentration (pressure) would be
highly desirable. However, prediction tools in asymmetric catal-
ysis are scarce and, so far, not able to anticipate such effects.
In this work, up to 21 substrates/ligands systems have been
investigated (Table 1). The observed variations of enantiomeric
excess with the hydrogen pressure is not as marked as in previ-
ous studies [16], only one reaction system leading to a large ee
variation from 6 to 50% ee (entry 21).
The substrates MAC and M-Acrylate display many simi-
lar behaviors (entries 1–14). Complete conversion (>96%) was
obtained for all experiments. The enantiomeric excess was
also constant with conversion. These closely related substrates
only differ with the presence of a phenyl group on the (␣)-
acylaminoacrylic ester. That can lead to weak ␲–␲ stacking
1.2. Evaluation
The study of the test reaction with different ligands was per-
formed in a stainless steel mini-autoclave of 15 mL. (Amtec;
http://www.amtec-chemnitz.de). This autoclave is equipped
with magnetic stirring (2200 rpm) and operates within a large
range of hydrogen pressure (1–30 bar). An evaluation of the
influence of the hydrogen pressure on the enantioselectivity
was performed on the BINAP derivatives chiral ligands com-
plexed with a rhodium precursor, [Rh(COD)2]BF4 and for three
substrates (Scheme 3).
Table 1
First, a study on the influence of the catalyst ageing on the
activity was performed. After 6 days storage at 0 ◦C, stock
solutions of catalyst (R)-5,5ꢀ-diperfluoroBINAP (10) and (R)-
5,5ꢀ-diacidesBINAP (6) display a decrease of activity of more
the 50% (Fig. 1). In order to avoid any interference with deac-
tivation, it was decided to only use freshly prepared solution (1
day) for all catalysts.
A recent work has demonstrated that in most cases (65%), an
increase in the hydrogen concentration leads to smaller enantios-
electivities and higher catalytic activities [16]. For production,
Influence of the hydrogen pressure on the enantiomeric excess
Entry
Substrate
Ligand
ee (%) at P (bar) Configuration
EeEFa
5
30
1
2
3
4
5
6
7
MAC
1
5
4
8
6
14
21
31
34
27
26
14
14
21
31
34
27
31
18
S
S
S
S
S
S
R
0
0
0
0
0
0.09
0.13
10
9
8
9
M-Acrylate
1
5
4
8
6
9
14
3
29
24
24
9
9
20
3
24
24
24
20
S
S
S
S
S
S
R
0
0.18
0
10
11
12
13
14
−0.09
0
10
9
0
0.38
15
16
17
18
19
20
21
Z-EMAP
1
5
4
8
6
66
60
63
77
70
21
6
57
60
63
72
60
50
50
R
R
R
R
R
R
S
−0.07
0
0
−0.03
−0.08
0.41
0.79
10
9
All reactions were carried out at 35 ◦C with [substrate] = 0.1 M and [cata-
lyst] = (10−3 to 10−4 M) under hydrogen pressure (5–30 bar) in 4 mL of degassed
MeOH. Yield are all >96% as checked by GC analysis.
Fig. 1. Activity of catalytic systems after 6 days computed in percent from initial
activity.
a
See text.

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M. Alame et al. / Journal of Molecular Catalysis A: Chemical 268 (2007) 205–212
Fig. 2. Comparison between MAC/M-Acrylate, conditions: 5 bar, T = 35◦C, methanol.
interactions with one of the phenyl groups of the BINAP (1)
derivatives. Such interaction may explain the better ee generally
obtained for the MAC albeit with slower reaction rates (Fig. 2).
Considering the effect of pressure on the enantiomeric excess
for the two substrates MAC and M-Acrylate, only a minor influ-
ence was observed under a large range of hydrogen pressure
(5–30 bar) for most of the Rh-BINAP derivatives. Positive effect
of hydrogen pressure on the ee was noticed only in the case of
electro-withdrawing groups like (CN (9), C8F17 (10)) [29,30]
on the 5,5ꢀ-position. Interestingly, only in one instance, ligand
(R)-5,5ꢀ-diphenylBINAP (8) and M-Acrylate, a decrease of ee
withincreasinghydrogenconcentrationwasobserved(entry11).
Thus, among the 14 reactions systems (entries 1–14), 9 are pres-
sure insensitive (with respect to ee), 4 give positive effects and
1 gives a negative effect.
ment” criteria, which varies between −1 and +1, is very useful
since it accounts for both the amplitude and the beneficial (+
sign) or detrimental (− sign) effect of increasing pressure. Thus
a quick look at eeEF provides many information on pressure
effects or other influences on ee. However, it is not adapted for
systems displaying configuration change (e.g. examples where
the sign of ee changes with pressure).
Considering all the ligands and substrates, the pressure effect
on ee is not very much marked. Out of the 21 reaction sys-
tems, 11 are not influenced by pressure (Table 1, eeEF = 0), 6
give positives effects (eeEF > 0) and 4 give negatives effects
(Table 1, eeEF < 0), with a remarkable positive effect (+0.79)
for entry 21 (6–50% ee). These results are very different from
those found in the literature, specially for the substrate methyl
´
Z-␣-acetamidocinnamate (MAC), for which a marked prefer-
The hydrogenation of the ethyl 4-methyl-3-acetamido-2-
pentanoate (Z-EMAP) [31] under the same conditions generally,
leads to higher ee’s, up to 77% (entry 18). Among the seven cat-
alytic systems, the distribution of positive effect (entries 20, 21),
negative effect (entries 15, 18, 19), and no effect (entries 15–21)
of hydrogen concentration (pressure) is roughly the same.
In order to quantify the observed influence of the hydrogen
pressure on enantiomeric excess, the following Enhancement
Factor (eeEF = enantiomeric excess Enhancement Factor) is pro-
posed:
ence for negative effect has been found (16 out of 19 cases)
[16]. More generally, an extensive literature search on pressure
effects on ee, including Ru and Rh and many different ligands
[16], has resulted in a non-equivalent distribution of pressure
effects: 53% with eeEF < 0, 15% with eeEF > 0 and 32% with
eeEF = 0.
Albeit the quantitative comparison with literature results
remains difficult since enantiomeric excess depend on many
other parameters (solvent, temperature, reactor, etc.), it should
be emphasized that the distribution of pressure effects (0% with
eeEF < 0, 72% with eeEF > 0, 28% with eeEF = 0) observed in
this study offers a striking contrast for which no explanation can
be obtained yet.
Finally, it is noteworthy that all substrates display a com-
mon feature in relation with the effect of the electronic density
at the phosphorus atoms on the activity and the enantios-
electivity. Indeed according to the electron-withdrawing or
electron-donating effect of the group introduced in the 5,5ꢀ-
position of BINAP (1), the enantiomeric excess varies. For the
acrylate substrate (Fig. 3), a regular variation of ee is observed
with respect to the electon-withdrawing properties of the ligands
eeP
eeP
− eeP
+ eeP
H
→∞
→∞
H
→0
→0
2
2
2
2
eeEFTheory
eeEFExp
=
=
,
H
H
eeP
eeP
− eeP
H
H
max
max
H
min
min
2
2
+ eeP
H
2
2
where eeP
and eeP
are the enantiomeric excess that
H
→0
H
→∞
2
2
would be obtained at very low hydrogen pressure and high
hydrogen pressure, respectively. In practice, eeEFexp is used in
which eeP
and eeP
are the ee obtained under the limits
H
max
H
min
2
of experim2ental pressure range for the study. This “enhance-

M. Alame et al. / Journal of Molecular Catalysis A: Chemical 268 (2007) 205–212
209
241 polarimeter. For the air-sensitive compounds, elemental
analyses were not performed. Mass spectra were recorded on
LCQ Advantage Thermofinnigan. Conversions and enantios-
electivities (ee 1%) were determined by GC on a lipodex
A (25 m × 0.25 mm) and CHIRASILVAL (25 m × 0.25 mm)
column. All the yields are isolated yields. Hydrogenation exper-
iments were performed in a mini-autoclave of stainless of 15 mL
from Amtec (http://www.amtec-chemnitz.de).
The compound Z-EMAP (ethyl 4-methyl-3-acetamido-2-
pentanoate) was prepared according to a published procedure
[31]. The compound M-Acrylate (methyl 2-acetamidoacrylate)
is commercially available (Aldrich).
Fig. 3. Effect of the groups in the 5,5ꢀ-position of BINAP on the enantiomeric
excess for M-Acrylate.
2.2. (R)-BINAPoxide (2)
In a 250 mL round-bottomed flask were placed either (R)-
BINAP(1)(3 g, 4.81 mmol)and100 mLofCH2Cl2. Themixture
was cooled to 0 ◦C and 10 mL of hydrogen peroxide H2O2 (35%)
then added. The mixture was stirred for 4 h. Then 100 mL of
water was added. Aqueous phases were extracted with 50 mL of
CH2Cl2. The organics phases were washed with 50 mL of aque-
ous sodium hydrogen sulfite solution dried over Na2SO4 and
evaporated to obtain a white solid (3.14 g, 4.8 mmol, quantita-
tive yield). 1H NMR (300 MHz, CDCl3): 6.80 (d, 4H, J = 3.7),
7.2–7.3 (m, 8H), 7.3–7.5 (m, 12H), 7.6–7.7 (m, 4H), 7.8–7.9
(m, 4H). 31P NMR (81 MHz, CDCl3): 28.67. Mp: 256–258 ◦C
[α]D = +198.1 (c 1, Benzene).
(Fig. 3). Attempts to find general correlations between the elec-
tronic properties of the ligands and ee have failed. This maybe
due to the difficulty to choose the right parameter to describe
the electronic property of the ligands. It is not possible to reduce
the complexity of electronic properties of such ligands and their
interaction with the metal centre to just one single parameter.
Theoretical chemistry may help to explain electronic properties
of the ligands.
In conclusion we have synthesized and tested various 5,5ꢀ-
disubstituted BINAP derivatives (seven catalytic systems) for
the Rh-catalyzed homogeneous asymmetric hydrogenation of
(␣)-acylaminoacrylate ester. We have shown that the BINAP
derivatives generally lead to higher ee than BINAP (1) the
best ligand being the 5,5ꢀ-diphenylBINAP (8). The nature of
the alkyl groups in the 5,5ꢀ-position or in the p-phenyl posi-
tion has a large influence on the variation of the enantiomeric
excess with hydrogen pressure: either a steric hindrance, or
an inductive electron-donating or electron-withdrawing effect
allows to reverse the influence of the hydrogen pressure on
the enantiomeric excess. More importantly, we have shown
that the introduction of electron donating or electron withdraw-
ing groups on the 5,5ꢀ-positions of the BINAP could have a
direct influence on the enantiomeric excess and on the activ-
ity of catalyst (under identical operating conditions). Further
work are devoted to the use of methods from theoretical chem-
istry to help understanding the results and built prediction
tools.
2.3. (R)-5,5ꢀ-DibromoBINAPO (3)
A solution of (R)-BINAPO (2) (4.8 g, 7.4 mmol) in 1,2
dichloroethane (45 mL) was added dropwise to a stirred reflux-
ing solution of 1,2 dichloroethane, (65 mL), Br2 (7.6 mL,
148 mmol, 20 eq.) and Fe (622 mg, 11.1 mmol, 1.5 eq.). After
addition was completed, the mixture was heated at reflux
overnight and then filtered to remove any solid iron. The organic
layer was washed sequentially with H2O, aqueous 1M sodium
hydrogensulfite, saturated sodium hydrogen carbonate solution
and brine. After drying over Na2SO4 the solvent was removed
to obtain a white solid (4.85 g 6 mmol, 80.7%). 1H NMR
(200 MHz, CDCl3): 6.62 (t, 2H, J = 15.0), 6.72 (d, 2H, J = 9.0),
7.2 7.5 (m, 20H), 7.55 (dd, 2H, J = 3.0, 1.0), 7.6–7.8 (m, 2H),
8.3 (dd, 2H, J = 1.7, 9.0). 13C NMR (75 MHz, CDCl3): 123.2,
126.5, 127.1, 127.3, 128.5, 128.7, 129.9, 131.6, 131.8, 132.1,
132.3, 132.5, 132.8, 132.9, 133.4, 135.0. 31P NMR (81 MHz,
CDCl3):29.20. [α]D = +97.7(c = 1, DMF). ESI+:MH+ = 813.32.
Mp: >300 ◦C. Calcd. C 65.05, H 3.72, P 7.62, Br 19.67; found
C 65.34, H 4.05, P 7.46, Br 19.44.
2. Experimental
2.1. General methods
˚
Solvents were dried with 4 A molecular sieves and dis-
tilled under an argon on LiAlH4 or purchased anhydrous
(Aldrich or Acros). For catalytic tests, solvents were deoxy-
genated by repeated evacuation and argon purging. NMR
spectra were recorded on Bruker AC 200 and DRX 300
apparatus. Chemical shifts are given in ppm using tetramethyl-
2.4. (R)-5,5ꢀ-DibromoBINAP (4)
In
a 250 mL round-bottomed flask under an inert
atmosphere fitted with a reflux condenser was placed, (R)-5,5ꢀ-
dibromoBINAPO (3) (3.9 g, 4.8 mmol), 65 mL of xylene and
phenylsilane (28 mL, 219 mmol) was added. The mixture is
stirred 10 min at room temperature after 10 min the trichlorosi-
lane (22.13 mL, 219 mmol) was added dropwise, heated to
silane as the internal standard for H and 13C NMR spectra,
1
and 31P NMR from H3PO4. Coupling constants are reported
in Hz. Optical rotations were measured on a Perkin-Elmer

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M. Alame et al. / Journal of Molecular Catalysis A: Chemical 268 (2007) 205–212
130 ◦C. After 15 h, the solution was cooled and stirred for 2 h,
and NaOH (75 mL, 40%) was added very dropwise, the layer
were separated and the aqueous phase washed with toluene; the
organic layers were collected and washed with water, then HCl,
and water. After drying over MgSO4 the solvent was removed
Mp: >300 ◦C. Calcd. C 74.4, H 4.3, O 12.9, P 8.3; found C 74.9,
H 4.6, O 12.5, P 8.1.
2.7. (R)-5,5ꢀ-DimethylBINAP (5)
1
to obtain a white solid (3.68 g, >98%). H NMR (300 MHz,
A 50 mL three-necked round-bottomed flask under
CDCl3):6.58(d, 10H, J = 4.3), 6.9–7.15(m, 14H), 7.45–7.55(m,
4H), 8.23 (d, 2H, J = 8.8). 13C NMR (75 MHz, CDCl3): 126.48,
127.57, 127.82, 128.54, 128.59, 128.64, 128.67, 128.72, 129.14,
130.9, 132.28, 133.14, 133.28, 133.41, 134.69, 134.83, 134.98.
31P NMR (81 MHz, CDCl3): 13.9. [α]D = +78.1 (c = 1, DMF).
HRLSIMS: MH+. Calcd. 778.06, found 778.026. Mp: >300 ◦C.
Calcd. C 67.71, H 3.87, Br 20.48, P 7.94; found C 67.1, H 4.0,
Br 20.8, P 7.5.
argon fitted with a low temperature thermometer, (R)-5,5ꢀ-
dibromoBINAP (4) (1.5 g, 1.923 mmol), THF (48 mL) was
added at −78 ◦C using dry liquid nitrogen/acetone. After
stirring at this temperature for 10 min, a solution of n-BuLi
(1.6 M in hexane, 2.4 mL, 3.846 mmol, 2 eq.) was slowly
added via syringe and it was stirred at this temperature for 3 h.
And then MeI (0.239 mL, 3.846 mmol, 2 eq.) was added. The
reaction mixture was stirred at this temperature for 1 h and
then warmed to room temperature and stirred overnight. After
removal of solvent, and LC separation on silica-gel column
(toluene/hexane) the final product was obtained as white solid
2.5. (R)-5,5ꢀ-DiacidesBINAP (6)
1
A
50 mL three-necked round-bottomed flask under
(1.2 g, 96% Rdt). H NMR (300 MHz, DMSO): 2.62 (s, 6H),
argon fitted with a low temperature thermometer, (R)-5,5ꢀ-
dibromoBINAP (4) (500 mg, 0.641 mmol), THF (6.4 mL) was
added at −78 ◦C. After stirred 10 min, a solution of n-BuLi
(1.6 M in hexane, 0.8 mL, 1.282 mmol, 2 eq.) was added very
dropwise and stirred 3 h at −78 ◦C. After 3 h the anion in
suspension was then added via a canula to a Dewar containing
an excess of crushed CO2 in Et2O (≈7 mL), this mixture gave
a pink colour. The mixture was left overnight to allow slow
degassing. 4 mL of HCl (0.5N) was then added to the mixture
so that the colour becomes clear yellow. The solvents were
then evaporated and the residue was dried to give a yellow
powder (416 mg, 91% Rdt). 1H NMR (300 MHz, DMSO):
6.86–7.03 (m, 10H), 7.43–7.46 (dd, 2H, J = 7, J = 1.0), 7.98
(dd, 2H), 8.9 (d, 2H), 13–13.5 (broad pic, 2 OH). 13C NMR
(75 MHz, DMSO): 125.07, 125.98, 128.2, 128.42, 128.76,
130.05, 130.65, 130.9, 131.53, 132.19, 132.39, 132.59, 132.88,
132.99, 133.23, 133.45, 133.65, 135.27, 135.44, 135.76,
135.91, 136.66, 136.91, 145.03, 168.64. 31P NMR (81 MHz,
DMSO): −15.7. [α]D = +82.3 (c = 1, DMF). HRLSIMS: MH+.
Calcd. 710.17760, found 710.17766. Mp: >300 ◦C. Calcd. C
77.74, H 4.54, O 9, P 8.72; found C 75.96, H 5.098, O 10.75, P
8.178
6.65–677 (m, 4H), 6.97–7.1 (m, 22H), 7.39 (dd, 2H, J = 6;
J = 2.3), 7.96 (d, 2H, J = 8.8). 13C NMR (75 MHz, CDCl3):
124.68, 125.9, 126.62, 127.85, 127.93, 128.38, 128.4, 128.73,
130.88, 133.18, 133.31, 133.44, 134.34, 134.48, 134.63. 31P
NMR (81 MHz, CDCl3): −14.7. [α]D = +117.7 (c = 1, CDCl3).
HRLSIMS: MH+. Calcd. 713.1588, found 713.1582. Mp:
>300 ◦C. Calcd. C 84.9, H 5.5, P 9.5; found C 85.0, H 5.9, P
8.9.
2.8. (R)-5,5ꢀ-DimethylBINAPO (5ꢀ)
In a 250 mL round-bottomed flask were placed either (R)-
5,5ꢀ-dimethylBINAP (5) (3 g, 4.6 mmol) and 100 mL of CH2Cl2.
The mixture was cooled to 0 ◦C and 10 mL of hydrogen per-
oxide H2O2 (35%) then added. The mixture was stirred for
4 h. Then 100 mL of water was added. Aqueous phases were
extracted with 50 mL of CH2Cl2. The organics phases were
washedwith50 mLofaqueoussodiumhydrogensulfitesolution,
dried over Na2SO4, evaporated to obtained a brown solid (3.14 g,
4.8 mmol, quantitative yield. 1H NMR (300 MHz, CDCl3):
2.75 (s, 6H), 6.7 (d, 2H, J = 14.7), 7.1–7.5 (m, 26H), 8.03 (d,
2H). 13C NMR (75 MHz, CDCl3): 123.397, 123.653, 125.540,
125.760, 127.717, 127.896, 127.953, 128.035, 128.142,
130.937, 131.041, 131.993, 132.178, 132.445, 132.651. 31P
NMR (81 MHz, CDCl3): 29.1. [α]D = +112.4 (c = 1, DMF).
ESI+: MH+ = 683.3. Mp: >300 ◦C. Calcd. C 80.9, H 55.3, O
4.6, P 9.0; found C 80.4, H 5.9, O 4.8, P 8.6.
2.6. (R)-5,5ꢀ-DiacidesBINAPO (6ꢀ)
In a 250 mL round-bottomed flask were placed either (R)-
5,5ꢀ-diacidesBINAP (6) (3 g, 4.2 mmol) and 100 mL of CH2Cl2.
The mixture was cooled to 0 ◦C and 10 mL of hydrogen peroxide
H2O2 (35%) then added. The mixture was stirred for 4 h. Then
100 mLofwaterwasadded. Aqueousphaseswereextractedwith
50 mL of CH2Cl2. The organic phases were washed with 50 mL
of aqueous sodium hydrogen sulfite solution, dried over Na2SO4
evaporated to obtain a shining brown solid (3.14 g, 4.8 mmol,
quantitative yield). 1H NMR (300 MHz, DMSO): 6.4–6.85 (m,
20H), 7.3–7.6 (m, 6H), 7.65 (d, 2H), 8.9 (d, 2H, J = 9.025),
13–13.5(broadpic, 2OH). 13CNMR(75 MHz, DMSO):125.77,
127.24, 127.99, 128.13, 130.63, 131.4, 131.58, 131.81, 132.02,
133.49, 168.45. 31P NMR (81 MHz, DMSO): 28.4. [α]D = −30
(c = 1, DMF). HRLSIMS: MH+. Calcd. 742.17, found 742.2.
2.9. (R)-5,5ꢀ-DiphenylBINAPO (7)
In a 250 mL round-bottomed flask under argon with a
reflux condenser was placed, (R)-5,5ꢀ-dibormoBINAPO (3) (1 g,
1.23 mmol), phenyl boronic acid (450 mg, 3.69 mmol, 3 eq.),
Pd[(PPh2)4] (113.6 mg, 0.0984 mmol, 0.08 eq.), Na2CO3 (5 mL,
2M, degassed), EtOH (10 mL), DME (60 mL) was heated to
reflux overnight. After cooled to room temperature, reaction
mixture was filtered through celite and washed with CH2Cl2
(30 mL). The filtrate was washed three times with water and
then dried on MgSO4. LC separation on silica-gel column

M. Alame et al. / Journal of Molecular Catalysis A: Chemical 268 (2007) 205–212
211
(ETOAc/cyclohexane) giving pure product as yellow powder
(quantitative yields). 1H NMR (300 MHz, CDCl3): 7.94 (d,
2H, J = 13.0), 6.6–7.39 (m, 38H). 13C NMR (75 MHz, CDCl3):
125.424, 126.98, 127.375, 127.824, 127.92, 128.06, 128.16,
128.29, 128.44, 130.3, 131.07, 131.96, 132.14, 132.25, 132.4,
132.61. 31P NMR (81 MHz, CDCl3): 28.99. [α]D = +155.2
(c = 1, DMF). ESI+: MH+ = 807.3. Mp: >300 ◦C. Calcd. C 83.3,
H 5.0, O 3.9, P 7.6; found C 83.0, H 5.3, O 4.1, P 7.3.
mixture of [Rh(COD)2]BF4 (1 eq. mmol) and BINAP deriva-
tives (1.05 eq. mmol) in degassed methanol at room temperature
1
during 1 h. They were stored at 0 ◦C before use. 31P{ H}
(81 MHz) NMR of the so prepared solutions displayed the
expected features: [RhCOD(R-BINAP)][BF4] (CD3OD; δ ppm
26.3 (d); JPRh = 147 Hz); [RhCOD(R-5,5ꢀ-DiMeBINAP)][BF4]
(CDCl3; δ ppm 25.7 (d); JPRh = 146 Hz); [RhCOD(R-5,5ꢀ-
DiBrBINAP)][BF4] (CDCl3; δ ppm 26.3 (d); JPRh = 148 Hz);
[RhCOD(R-5,5ꢀ-diacideBINAP)][BF4] (CD3OD; δ ppm 26.3
(d); JPRh = 147 Hz); [RhCOD(R-5,5ꢀ-diperfluoroBINAP)][BF4]
(CDCl3; δ ppm 26.3 (d); JPRh = 148 Hz); [RhCOD(R-5,5ꢀ-
dicyanoBINAP)][BF4] (CD2Cl2; δ ppm 25 (d); JPRh = 137 Hz);
[RhCOD(R-5,5ꢀ-DiPhBINAP)][BF4] (CDCl3; δ ppm 26 (d);
JPRh = 148 Hz).
2.10. (R)-5,5ꢀ-DiphenylBINAP (8)
In a 25 mL round-bottomed flask under an inert atmo-
sphere fitted with a reflux condenser was placed, (R)-5,5ꢀ-
diphenylBINAPO (7) (626 mg, 0.776 mmol), 10.5 mL of xylene
and phenylsilane (3.9 mL, 31.06 mmol, 40 eq.) was added. The
mixture is stirred 10 min at room temperature after 10 min the
trichlorosilane (3.1 mL, 31.06 mmol, 40 eq.) was added drop-
wise, heated to 130 ◦C, after 15 h, the solution was cooled and
stirred for 2 h, and NaOH (11 mL, 40%) was added very drop-
wise, the layer were separated, the aqueous phase washed with
toluene (5 mL) and the organic layer were collected, washed
with water, HCl, and water. After drying over MgSO4 the sol-
vent is removed to obtain a yellow solid (565 mg, 94%) 1H NMR
(300 MHz, CDCl3): 6.84–7.49 (m, 38H), 7.8 (d, 2H, J = 8.6).
13C NMR (75 MHz, CDCl3): 125.66, 126.59, 127.64, 127.96,
128.04, 128.46, 128.6, 128.86, 130.67, 130.98, 133.24, 133.37,
133.5, 134.54, 134.7, 134.85. 31P NMR (81 MHz, CDCl3):
−14.07. [α]D = +60.3 (c 1, DMF). HRLSIMS: MH+. Calcd.
774.26, found 774.26. Mp: >300 ◦C. Calcd. C 86.8, H 5.2, P
7.9; found C 86.4, H 5.4, P 7.6.
3. Hydrogenation
A solution of 1a (1b) (0.1 M) in MeOH (4 mL) was
stirred (2200 rpm) at 35 ◦C with the catalyst [Rh(BINAP
derivatives)(COD)]BF4 (10−3 or 10−4 M) under H2 (5 or
30 bar). The conversion and enantiomeric excess (ee 1%) were
determined from on time sampling of the reaction mixture by GC
analysis on lipodex A (25 m × 0.25 mm) and CHIRASILVAL
(25 m × 0.25 mm) columns.
Acknowledgements
´
Funding from the CNRS and the Ecole Superieure de Chimie
Physique Electronique de Lyon (ESCPE) is acknowledged.
Many thanks also to Mr. Bertrand Baubet for experimental work.
2.11. Synthesis of methyl-Z-α-acetamidocinnamate (MAC)
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of diethylether. The solution is frozen for recrystallization. The
recrystallization is conducted three times for a yield of 52%.
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