2,2′-Bis-[bis(4-substituted-phenyl)phosphino]-1,1′-binaphthyl derivatives in Rh(I)-catalyzed hydrogenation of acetamidoacrylic acid derivatives: Electronic effects

Article abstract of DOI:10.1016/j.molcata.2007.02.027

Electronic effects of electron-donating and electron-withdrawing substituents at the para position of the phenyl moieties of BINAP ligands were studied towards asymmetric hydrogenation of α-(acylamino)acrylic acids. Enantiomeric excesses varied as a linear relationship towards Hammett coefficients σ_p of electron-donating groups between 0 and -0.63.

Full text of DOI:10.1016/j.molcata.2007.02.027

Journal of Molecular Catalysis A: Chemical 271 (2007) 18–24
2,2ꢀ-Bis-[bis(4-substituted-phenyl)phosphino]-1,1ꢀ-binaphthyl
derivatives in Rh(I)-catalyzed hydrogenation of
acetamidoacrylic acid derivatives: Electronic effects
a
b
b
b,∗
´
M. Alame , M. Jahjah , S. Pellet-Rostaing , M. Lemaire
,
V. Meillea, C. de Bellefona,∗
a Laboratoire de Ge´nie des proce´de´s Catalytiques, UMR 2214, CNRS-CPE Lyon, Universite´ Claude Bernard Lyon 1,
43 Bd du 11 Novembre 1918, 69622 Villeurbanne, France
b Laboratoire de Catalyse et Synthe`se Organique, UMR 5181, CPE-Lyon, Universite´ Claude Bernard Lyon 1,
43 Bd du 11 Novembre 1918, 69622 Villeurbanne, France
Received 21 December 2006; received in revised form 16 February 2007; accepted 19 February 2007
Available online 23 February 2007
Abstract
Electronic effects of electron-donating and electron-withdrawing substituents at the para position of the phenyl moieties of BINAP ligands were
studied towards asymmetric hydrogenation of ␣-(acylamino)acrylic acids. Enantiomeric excesses varied as a linear relationship towards Hammett
coefficients σp of electron-donating groups between 0 and −0.63.
© 2007 Elsevier B.V. All rights reserved.
Keywords: BINAP; Enantioselectivity; Hydrogenation; Electronic effect; Rhodium
grafted in the 5,5ꢀ position of BINAP affected the enantiose-
lectivity of asymmetric hydrogenation of ␣-(acylamino)acrylic
acids [15]. On the other hand, modification of the para
position of the phenyl groups results in the change in the
electronic density onto the phosphorus heteroatom [16–20].
Thus, electronic donor-acceptor properties of BINAP and
its derivatives (p-Tol-, p-OMe-, p-F- and p-Cl-BINAP) were
investigated towards the activity of rhodium and ruthenium
catalysts. Generally, the ␲-acidic character of the diphos-
phine ligand incorporating electron-withdrawing substituents
resulted in decreased catalytic activity and stereoselectivity of
the asymmetric hydrogenation reactions [21,22]. Nevertheless,
Genet described the use of an electrodeficient atropoisomeric
diphosphane, difluorphos [23] which allowed for high lev-
els of enantioselection in the hydrogenation of ␤-ketoesters.
Electron-donating substituents exert positive effects on catalytic
activity and stereoselectivity of these reactions. In order to
investigate the effects of substituents on the four phenyl rings
of BINAP, we examined the electronic effects on the enan-
tioselectivity of the Rh(I)-catalyzed asymmetric hydrogenation
of ␣-(acylamino)acrylic acids 1 (Scheme 1). Substituents,
which could influence the electronic features of the catalysts,
1. Introduction
Chiral diphosphines play a central role as ligands for tran-
sition metals in homogeneous catalysis [1,2]. Among them,
atropoisomericdiaryl-corediphosphaneslikeBINAPareattract-
ing continued interest in view of their exceptional ability to
induce asymmetry in transition metal-catalyzed reaction [3].
Atropoisomery is one of the most powerful tools for enantios-
election. As described with MeO-BIPHEP [4–6], SYNPHOS
[7,8] and SEGPHOS [9], BINAP [10,11] allows the formation
of catalytic sites in which the chiral environment is controlled
by classical steric and electronic factors, but also by the dihedral
angle between the two aromatic cycles of the binaphthyl moiety
[12].
Conveniently modification of the 3,3ꢀ or 4,4ꢀ positions of the
naphthyl skeleton of BINAP influences strongly both the elec-
tronic density and the steric hindrance at the phosphorus atom
[13,14]. According to the electron-donating or -withdrawing
effects, we recently observed that the nature of substituents
∗
Corresponding authors. Tel.: +33 472 43 14 07; fax: +33 472 43 14 08.
1381-1169/$ – see front matter © 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.molcata.2007.02.027

M. Alame´ et al. / Journal of Molecular Catalysis A: Chemical 271 (2007) 18–24
19
Scheme 1. Hydrogenation of ␣-(acylamino)acrylic acids 1a and 1b.
were incorporated at the p-position of the phenyl groups of
BINAP.
water (50 mL), ethyl acetate (100 mL) and HCl 10% (50 mL)
were successively added. The mixture was stirred at room tem-
perature for 30 min. The reaction mixture was portioned, and
the aqueous layer was extracted three times with ethyl acetate
(60 mL). The combined organic layers were washed with HCl
2% (200 mL) and Brine (100 mL), and dried over anhydrous
magnesium sulphate. The solution was then filtered and the fil-
trate concentrated under reduced pressure. The obtained residue
was purified by column chromatography on silica gel using
ethyl acetate as the eluent to give the product (11 g, white crys-
Already described with high e.e. when 1 mol% of [Rh(-
binap)(norbornadiene)]ClO4 was used under 3–4 atm [24,25],
the generally low enantioselectivities of this reaction with less
than 0.1 mol% of Rh(I) is actually a desirable property because,
in principle, statistically significant changes in enantioselectiv-
ities can be expected.
To better understand the effects of para-substituents on
metal coordination, spectral data of the carbonyl stretching
frequencies of RhCl(BINAP)-(CO) species were frequently
studied in asymmetric reactions [20,23]. In the hydrogenation
of 2-benzamidomethyl-3-oxobutanoate catalyzed by cationique
BINAP-ruthenium(II) complexes, Takaya et al. described a
linear relationships between the values of νCO and Hammet
σ-values values of BINAP derivatives [24,25]. Since Jacobsen
studied the effect of electronic properties of salen ligands in the
asymmetric epoxidation [26,27], recent examples demonstrated
that electronic tuning of a ligand system could be connected to
the enantioselectivity [28,29] with linear relationships in many
cases [30–33].
1
tal, 54%). Mp = 124–125 ◦C; H NMR (300 MHz, CDCl3): δ:
3.71 (s, 6H, OCH3), 6.92 (d, J = 7 Hz, 4H, Harom), 7.55 (dd,
J = 14.2, 7 Hz, 4H, Harom), 7.94 (d, J = 480 Hz, 1H, HP); 13C
NMR (300 MHz, CDCl3): 55.8, 114.7 (d, J = 20), 123.5 (d,
1
J = 110), 133.0 (d, J = 20), 163.2 (d, J = 10); 31P{ H} NMR
(81 MHz, CDCl3): δ: 20.9 (s).
2.3.2. Bis(4-methoxyphenyl)phosphine-borane complex 3
A solution of cerium chloride (11.27 g, 45.75 mmol) in THF
(35 mL) was stirred under Ar at room temperature (25 ◦C) for
30 min. Sodium borohydride (1.8 g, 47.28 mmol) was added and
the mixture was stirred at room temperature for 1 h. Then, bis(4-
methoxyphenyl)phosphine oxide (4 g, 15.25 mmol) and lithium
alumina hydride (0.7 g, 18.3 mmol) were successively added at
5 ◦C and the mixture was stirred at room temperature for 3 h.
3N NaOH (50 mL) was added at 3 ◦C, followed by ethyl acetate
(50 mL), water (20 mL) and cellite. The mixture was stirred at
room temperature for 30 min and then filtered. The filtrate was
partitioned, and the aqueous layer was extracted three times with
ethylacetate(90 mL). Thecombinedorganiclayerswerewashed
with water (2 × 100 mL), Brine (100 mL), dried over anhydrous
magnesium sulphate, filtered and concentrated under reduced
pressure. The residue was purified by column chromatography
on silica gel (eluent n-hexane/ethyl acetate 5/1 → 2/1) to give
3 (2.4 g, white crystal, 60%). 1H NMR (300 MHz, CDCl3):
0.43–1.57 (m, 3H, BH3), δ: 3.82 (s, 6H, OCH3), 6.24 (dq,
2. Experimental
2.1. Chemicals
The solvents used in the syntheses were purchased as extra
dry from Acros organics and Aldrich and used without further
purification. Commercially available starting materials (organic
and organomettalic reagents) were used as received, unless
stated. 5aand5bwerepurchasedfromStemChemicals. (R)-2,2ꢀ-
bis(trifluoromethanesulfonyloxy)-1,1ꢀ binaphthyl was prepared
as described in literature [34].
2.2. Characterizations
1H, 13C and 31P NMR spectra were recorded with a Bruker
AM300 (1H, 300 MHz, 13C, 75 MHz) in CDCl3 as solvent.
Polarimetric measurements were performed on a Perkin-Elmer
241 apparatus, at ambient temperature).
J = 377.9, 6.78 Hz, 1H, HP), 6.95 (dd, J = 8.71, 1.72 Hz, 4H,
1
H
arom), 7.53–7.60 (m, 4H, Harom); 31P{ H} NMR (81 MHz,
CDCl3): δ: −4.53 to 2.73 (m), −1.26 to 0.40 (m), −4.15 (m).
2.3.3. (R)-2,2ꢀ-bis[bis(4-methoxyphenyl)phosphino]-1,1ꢀ-
binaphthyl 5c
2.3. Synthesis of BINAP 5c and 5d
Under an argon atmosphere, to a solution (5 mL) of [1,2-bis-
(diphenylphosphino)-ethane]dichloronickel (53 mg, 0.1 equiv-
alent), (R)-2,2ꢀ-bis(trifluoromethanessulfonyloxy)-1,1ꢀbinap-
hthyl (500 mg, 0.91 mmol) and 1,4-diazabicyclo[2,2,2]octane
(613 mg, 6.0 equivalents) in DMF was added at room tem-
perature bis(4-methoxyphenyl)phosphine-borane complexe
(543 mg, 2.3 equivalent) and the mixture was stirred at room
temperature for 30 min and then at 110 ◦C for 48 h. DMF was
2.3.1. Bis(4-methoxyphenyl)phosphine oxide
A solution of magnesium (4.125 g, 0.171 mol) in THF
(10 mL)wasstirredunderAratroomtemperaturefor1 h. Asolu-
tion of 4-bromoanisole (19.53 mL, 0.156 mol) in THF (30 mL)
was slowly added at 45 ◦C and the mixture was stirred at 5 ◦C for
1 h. Then, diethyl phosphite (10 mL, 0.78 mol) was added and
the mixture was stirred at 45 ◦C for 2 h. After cooling (0 ◦C),

20
M. Alame´ et al. / Journal of Molecular Catalysis A: Chemical 271 (2007) 18–24
evaporated under reduced pressure and methanol was added to
the residue to give the title compound 5c (444 mg, white crystal,
30 min. Sodium borohydride (1.22 g, 37.8 mmol) was added and
the mixture was stirred at room temperature for 1 h. Then bis(4-
dimethylaminophenyl)phosphine oxide (3 g, 10.4 mmol) and
lithium alumina hydride (0.47 g, 12.48 mmol) were successively
added at 5 ◦C and the mixture was stirred at room temperature
for 3 h. 3N NaOH (40 mL) was added at 3 ◦C, followed by ethyl
acetate (40 mL), water (20 mL) and cellite. The mixture was
stirred at room temperature for 30 min and then filtered. The fil-
trate was partitioned, and the aqueous layer was extracted three
times with ethyl acetate (60 mL). The combined organic layers
were washed with water (2 × 30 mL), Brine (2 × 30 mL), dried
over anhydrous magnesium sulphate, filtered and concentrated
under reduced pressure. The residue was purified by column
chromatography on silica gel (eluent n-hexane/ethyl acetate,
66%). [α]2D5 = +107.6 (c 0.4, CHCl3); H NMR (300 MHz,
1
CDCl3): δ: 3.73 (s, 12H, CH3), 6.64 (d, J = 8.35 Hz, 4H, Harom),
6.69 (d, J = 8.19 Hz, 4H, Harom), 6.80 (d, J = 8.49 Hz, 2H,
Harom), 6.92–7.03 (m, 10H, Harom), 7.30–7.38 (m, 2H, Harom),
7.40–7.45 (m, 2H, Harom), 7.82 (d, J = 8.13 Hz, 2H, Harom),
1
7.87(d, J = 8.52 Hz, 2H, Harom); 31P{ H} NMR (81 MHz,
CDCl3): δ: −16.86(s).
2.3.4. (R)-2,2ꢀ-bis[bis(4-hydroxyphenyl)phosphino]-1,1ꢀ-
binaphthyl 5d
A solution of (R)-2,2ꢀ-bis[bis(4-methoxyphenyl)phosphino]-
1,1ꢀ-binaphthyl (433 mg, 0.56 mmol) in dry CH2Cl2 (20 mL)
was cooled at 0 ◦C. A 1 M solution of BBr3 in CH2Cl2 (5.6 mL,
5.6 mmol) was added, and the reaction mixture was stirred at
0 ◦C for 1 h, and then at room temperature for 24 h. The solu-
tion was cooled to 5 ◦C and CH3OH (10 mL) was carefully
added. After removal of the organic solvents, the residue was
recrystallized from hot CH3OH (10 mL) by adding cold water
(5 mL) to give 5d (380 mg, 95%). White solid; mp >220 ◦C;
[α]2D5 = +29 (c 0.9, MeOH); 1H NMR (300 MHz, DMSO-d6):
δ: 6.55 (d, J = 8.6 Hz, 2H, Harom), 6.65–6.69 (m, 6H, Harom), 6.82
(bt, J = 7.5 Hz, 2H, Harom), 7.13 (dd, J = 11.5, 8.6 Hz, 4H, Harom),
7.31 (dd, J = 11.5, 8.6 Hz, 2H, Harom), 7.38 (bt, J = 7.5 Hz, 2H,
1/1) to give 4 (0.6 g, white crystal, 20%). Mp = 142.5 ◦C; H
1
NMR (300 MHz, CDCl3): δ: 0.41–1.34 (m, 3H, BH3), 3.07
(s, 12H), 6.3 (dq, J = 376.1 Hz, 1H, HP), 7.5 (d, J = 8.81 Hz,
1
4H, Harom), 7.53 (d, J = 8.79 Hz, 4H, Harom); 31P{ H} NMR
(81 MHz, CDCl3): δ: −6.38–4.73 (m), −3.3–1.6 (m).
2.3.7. (R)-2,2ꢀ-bis[bis(4-dimethylaminophenyl)phosphino]-
1,1ꢀ- binaphthyl 5e
To
a solution of [1,2-bis(diphenylphosphino)-ethane]
dichloronickel (164 mg, 0.311 mmol) in dry DMF (15 mL), (R)-
2,2ꢀ-bis(trifluoromethanesulfonyloxy)-1,1ꢀ binaphthyl (1.7 g,
3.1 mmol) and 1,4-diazabicyclo[2,2,2]octane (2.1 g, 18.7 mmol)
and bis(4-dimethylaminophenyl)phosphine–borane complexe
(2.05 g, 7.16 mmol) were added under Ar at room temperature.
The mixture was stirred at room temperature for 30 min and
then at 110 ◦C for 5 days. DMF was evaporated under reduced
pressure. One millilitre EtOAc and 10 mL methanol were
added to the residue to give the title compound 5e (1.3 g, white
crystal, 52.9%). [α]2D5 = 13.05 (c 0.95, CH2Cl2); 1H NMR
(300 MHz, CDCl3): δ: 2.9 (s, 24H, CH3), 6.42 (d, J = 6.8 Hz,
4H, Harom), 6.52–6.6 (m, 4H, Harom), 6.75–7.05 (m, 12H,
Harom), 7.13–7.25 (m, 2H, Harom), 7.5 (d, J = 7.13 Hz, 2H,
H
arom), 7.44 (dd, J = 11.5, 8.6 Hz, 2H, Harom), 7.86–7.92 (m, 4H,
Harom), 9.95 (s, 4H, OH); 31P { H}NMR (81 MHz, DMSO-d6):
1
−18.42(s).
2.3.5. Bis(4-dimethylaminophenyl)phosphine oxide
A solution of magnesium (2.0 g, 81.6 mmol) in THF (5 mL)
was stirred under Ar at room temperature for 1 h. A solution
of 4-bromo-N,N-dimethylaniline (14.85 g, 74.2 mmol) in THF
(25 mL) was slowly added at 45 ◦C and the mixture was stirred at
5 ◦C for 1 h. Then, diethyl phosphite (4.75 mL, 37.1 mmol) was
added and the mixture was stirred at 45 ◦C for 2 h. After cool-
ing (0 ◦C), water (25 mL), ethyl acetate (50 mL) and HCl 10%
(25 mL) were successively added. The mixture was stirred at
room temperature for 30 min. The reaction mixture was neutral-
ized with NaOH, portioned, and the aqueous layer was extracted
three times with ethyl acetate (30 mL). The combined organic
layers were washed with HCl 2% (100 mL) and Brine (50 mL),
and dried over anhydrous magnesium sulphate. The solution was
then filtered and the filtrate concentrated under reduced pres-
sure. The residue was recrystallized from t-butylmethyl ether
to give the product (6.25 g, white crystal, 58.4%). Mp = 152 ◦C;
1H NMR (300 MHz, CDCl3): δ: 3.01 (s, 12H, CH3), 6.71 (d,
J = 8.94 Hz, 2H, Harom), 6.72 (d, J = 8.94 Hz, 2H, Harom), 7.48
(d, J = 8.91 Hz, 2H, Harom), 7.52 (d, J = 8.88 Hz, 2H, Harom), 7.96
(d, J = 470 Hz, 1H, HP); 13C NMR (300 MHz, CDCl3): 40.38,
111.72, 111.90, 116.88, 118.37, 132.54, 132.72, 153.03, 153.06;
H
arom), 7.75 (d, J = 7.55 Hz, 2H, Harom), 7.82 (d, J = 8.29 Hz,
2H, Harom); 31P{ H} NMR (81 MHz, CDCl3): δ: −17.5 (s).
1
2.4. Synthesis of catalysts 6a–fꢀ
2.4.1. [Rh(BINAP)(COD)]BF4 6a–6e
Stock solution of 6a–e catalysts were prepared in a glove
box under argon by stirring a mixture of [Rh(COD)2]BF4
(1 eq/mmol) and 5a–d and 5f derivatives (1.05 eq mmol) in
degassed methanol at room temperature during 1 h. Catalysts
were stored in methanolic solution at 0 ◦C before used.
2.4.2. [Rh(BINAP)(COD)]BF4 6fꢀ
To a methanolic solution of 6e (0.2 mmol), MeOSO2CF3
(0.8 mmol) was added and the mixture was stirred at room tem-
perature for 5 h. Catalyst was stored in methanolic solution at
0 ◦C before used.
1
31P{ H} NMR (81 MHz, CDCl3): δ: 23.3 (s).
2.3.6. Bis(4-dimethylaminophenyl)phosphine-borane
complex 4
2.5. Hydrogenation
A solution of cerium chloride (7.69 g, 31.2 mmol) in THF
Hydrogenation experiments were performed in a mini-
autoclave of stainless of 15 mL from Amtec (www.amtec-
(35 mL) was stirred under Ar at room temperature (25 ◦C) for

M. Alame´ et al. / Journal of Molecular Catalysis A: Chemical 271 (2007) 18–24
21
Scheme 2. Synthesis of ligands 5d and 5e.
chemnitz.de). Conversions and enantiomeric excesses were
determined by GC analysis on a chiral CHIRASILVAL column.
A solution of 1a (1b) (0.1 M) in MeOH (4 mL) was stirring
(2200 rpm) at 35 ◦C with catalysts 6a–fꢀ (10−3 or 10−4 M) under
Rh(I)-BINAP complexes 6a–e were used in the hydrogena-
tion of substituted olefins 1a and 1b, and the results were given
in Table 1. Catalysts 6a–e were prepared in situ by stirring a
solution of [Rh(COD)2]BF4 precursor and the diphosphine lig-
ands (Scheme 3) prior to introduction of the olefin and being
pressurized under H2.
H2 (PH = 5 or 30 bar). After the reaction time, the autoclave was
2
cooled to room temperature and depressurized. Conversion and
enantiomeric excess were determined from on time sampling
of the reaction mixture by GC analysis on a CHIRASILVAL
column.
3.2. Catalytic hydrogenation
Each catalyst/H2 pressure/substrate ((␣-acylamino)acrylic
esters 1a and 1b) combination was examined under our hydro-
genation conditions, and the results are presented in Table 1.
Regardless of the ligands and the hydrogen pressure were
used, methyl-2-acetamidoacrylate 1b was hydrogenated faster
than (Z)-methyl-␣-acetamidocinnamate 1a due to the higher
reactivity of 1b. E.e’s were moderate and varied from 15% in
favour of the (S) enantiomer to 57% in favour of the (R) enan-
tiomer with very low values of 5 and 3% of (S) product with
Tol-BINAP 6b (Fig. 1). Moreover, the effects of hydrogen pres-
sure on the hydrogenation of 1a seemed to be marginal with
maximum variations of 3% with 6e. On the contrary, increas-
ing the H2 pressure from 5 to 30 bars led to more significant
variations of e.e.s in the hydrogenation of 1b (from 1 to 9%).
3. Results and discussion
3.1. Preparation of the catalysts
Although 5a-b were commercially available, 5c was obtained
by a coupling reaction from the di-p-anisylphosphine-borane 3
[35] (Scheme 2) and 2 in the presence of DABCO and NiCl2dppe
in DMF, as an alternative faster and more efficient route than
those proposed in literature [19,36].
Treatment of 5c with BBr3 afforded 5d [36] in quantitative
yield. 5e [37] was prepared in the same manner from the p-
anilinephosphine [38] via the coupling reaction between 2 and
the p-anilinephosphine borane analogue 4 [37].
Table 1
Asymmetric hydrogenation of 1a and 1b
39–42
Catalyst
6a
Substratea
Timeb (min)
Conversionb (%)
Eeb,c (% R)
Log[R/S)X/(R/S)H]b
σp
1a
1b
23(2.5)
1.5 (0.6)
99(98)
99(99)
−14 (−14)
−15 (−8)
0(0)
0(0)
0
1a
1b
9(2)
1 (0.6)
98(98)
99(99)
− 5 (−5)
0.065 (0.73)
0.106 (0.104)
−0.14
−0.28
−0.38
−0.63
6b
6c
6d
− 3 (− 2)
1a
1b
26.5 (7)
1(0.6)
99(99)
96(96)
15(14)
13(18)
0.242 (0.241)
0.252 (0.228)
1a
1b
22(6)
2 (0.6)
97(97)
99(99)
37(36)
30(39)
0.458 (0.445)
0.401 (0.431)
1a
1b
24(5)
2 (0.6)
97(95)
99(96)
57(54)
48(48)
0.679 (0.642)
0.587 (0.518)
6e
a
With 1a: Rh(I) 0.1 mol%; with 1b: Rh(I) 0.01 mol%.
Pressure, 5 bar. Values in parentheses refer to results obtained at 30 bar.
Determined by chiral HPLC.
b
c

22
M. Alame´ et al. / Journal of Molecular Catalysis A: Chemical 271 (2007) 18–24
Scheme 3. General procedure of BINAP complexes synthesis.
Fig. 1. H2 pressure effect on the e.e.s of the hydrogenation of 1a and 1b.
3.3. Electronic effects
for salen or porphyrins type catalysts [30,31]. Thus, lower reac-
tivity leads to a comparatively late transition state accompanied
of a higher selectivity. The largest |ρ| value of 1a suggested that
the interaction between catalyst and substrate was the great-
est, because the lower reactivity of 1a leads to a transition state
with the most product-like conformation. Nevertheless, with
ρ = log[(R/S)X/(R/S)H]/␴ values close to 1, it seemed to be pos-
sible and interesting to correlate directly the R/S ratios with σp
(Fig. 3).
Indeed, when the R/S are reported were reported versus Ham-
mett coefficients (Fig. 3), the same trend was observed with
electron-donating groups on the catalyst leading to higher enan-
tioselectivities. With five-point Hammett plots, we found clear
linear relationships (R2 > 0.95) between the electronic constants
and enantioselectivities. As shown in Fig. 3, R/S ratios decreased
following the sequence NMe2 > OH > OMe > Me > H. With ρ
These results showed that the efficiency and the sense of the
enantioselective hydrogenation were highly influenced by the
electronic density on the phosphorus atom of the catalyst.
From these data, we determined the influence of the elec-
tronic density of the metal catalyst on the enantiomeric ratio,
i.e. R/S. When the results were reported in Hammett plots of
log[(R/S)X/(R/S)H] versus σp [39–42] (Fig. 2), the slope of the
obtained strengths (ρ) could be interpreted as the reflection
of the influence of the p-substituents on the BINAP towards
the sensitivity of the asymmetric induction. With a ρ value of
−1.03, asymmetric hydrogenation of 1a could be considered to
be more influenced by the nature of the BINAP catalyst than the
hydrogenation of 1b with a smaller value of −0.92. This can be
explained in terms of the Hammond postulate, as demonstrated
Fig. 2. log[(R/S)X/(R/S)H] as a function of phosphine electronics.

M. Alame´ et al. / Journal of Molecular Catalysis A: Chemical 271 (2007) 18–24
23
Fig. 3. R and S ratio as a function of phosphine electronics.
Scheme 4. Hydrogenation of 1a and 1b with the ammonium BINAP derivative prepared in situ.
values of σp N+(CH3)3 and σp (NMe2) of 0.82 and −0.63, res-
pectively. Then, the calculated Hammett constant was 0.45 and
the corresponding e.e. (experimental) fits with the straight line.
From the knowledge of the σp of the phenylene substitutents,
it was possible to predict the e.e.s of the hydrogenation reaction
values of −4.76 and −3.34, respectively for 1a and 1b, we
confirmed that the asymmetric induction in the hydrogenation
reaction of (␣-acylamino)acrylic esters was governed by the
electronic density on the phosphorus atom with a higher influ-
ence in the asymmetric induction of 1a.
In order to confirm the surprising change in the enantios-
electivity, a BINAP bearing electron-withdrawing group was
evaluated.
When the Rh-catalyst 6e was treated in situ with methyl tri-
fluoromethanesulfonate before its use in the hydrogenation of 1a
and 1b, N-acetyl-l-phenylalanine methyl ester and N-acetyl-l-
alanine methyl ester were predominantly obtained with e.e.s of
35 and 38%, respectively (Scheme 4). This supplementary result
confirmed the change in the sense of the enantioselectivity from
electron-donating to electron-withdrawing substituents.
When e.e.s were reported as a function of Hammett coef-
ficients (Fig. 4), a linear relationship was also observed with
ligands 6a–e. The experimental e.e. with the implied ammonium
ligand 6f does not respect the linearity and corresponds to an e.e.
theoretically obtained with the ligand 6f’, incorporating three
ammonium groups and one NMe2. If we consider that 6e was
partially alkylated, the medium Hammett coefficient of 6f’ could
be given by σp(medium) = [3σp(N+(CH3)3 + σp(NMe2)]/4 with
Fig. 4. E.e. as a function of phosphine electronics in the hydrogenation of 1b.

24
M. Alame´ et al. / Journal of Molecular Catalysis A: Chemical 271 (2007) 18–24
of (␣-acylamino)acrylic esters. Thus, a theoretical e.e. of 65%
of the (S) enantiomer would be reached with the ammonium
catalyst 6f.
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4. Conclusions
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In conclusion, the electronic effects of electron-donating sub-
stituents at the para position of the phenyl moieties of BINAP
ligands have been evaluated towards asymmetric hydrogena-
tion of ␣-(acylamino)acrylic acids. Enantiomeric excesses were
highly dependant of the nature of the substitutents and varied
experimentally from 38% of (S) compound to 57% of (R) com-
pound as an unexpected linear relationship towards Hammett
coefficients (between −0.63 and 0). The changes in the sense
of the enantioselectivity can be explained from electronic fac-
tors as confirmed when electron-withdrawing substituents were
introduced on the phenyl fragment. The change in the sense of
the enantioselectivity could be connected to favoured kinetic or
thermodynamic transition states. The modification of the dihe-
dral angle between the two naphthyl moieties which is known
to be a nonetheless important parameter [7] certainly influences
the selectivity. Future work aiming at using molecular modelling
for a more fundamental understanding of these results and for
more directed asymmetric catalyst design is ongoing.
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