The synthesis of new chiral phosphine-phosphinites, phosphine- phosphoramidite, and phosphine-phosphite ligands and their applications in asymmetric hydrogenation

Article abstract of DOI:10.1016/j.tetasy.2004.05.046

New chiral phosphine-phosphinite, phosphine-phosphoramidite ligands and phosphine-phosphite 1a, 1b, 2 and 3 have been synthesized and examined in the enantioselective hydrogenation of dehydroamino acid derivatives and α-aryl enamides. The results demonstr

Full text of DOI:10.1016/j.tetasy.2004.05.046

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 2273–2278
The synthesis of new chiral phosphine–phosphinites,
phosphine–phosphoramidite, and phosphine–phosphite
ligands and their applications in asymmetric hydrogenation
a
a
a
a
Xian Jia,a,c Xingshu Li,a,b, Wing Sze Lam, Stanton H. L. Kok, Lijin Xu, Gui Lu,
*
Chi-Hung Yeunga,* and Albert S. C. Chana,*
aOpen Laboratory of Chirotechnology of the Institute of Molecular Technology for Drug Discovery and Synthesis and
Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China
bDepartment of Chemistry, The South-West Nationality College, Chengdu, 610041, China
cShenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China
Received 3 May 2004; accepted 21 May 2004
Abstract—New chiral phosphine–phosphinite, phosphine–phosphoramidite ligands and phosphine–phosphite 1a, 1b, 2 and 3 have
been synthesized and examined in the enantioselective hydrogenation of dehydroamino acid derivatives and a-aryl enamides. The
results demonstrate that both rhodium-1b and rhodium-2 complexes were highly efficient catalysts in asymmetric hydrogenation
reactions (up to 99.6% ee was obtained).
ꢀ 2004 Elsevier Ltd. All rights reserved.
1. Introduction
metal-catalyzed asymmetric synthesis over the last three
decades.3 High enantioselectivities were obtained in the
asymmetric hydrogenation of prochiral olefins using
rhodium catalysts containing chiral diphosphine ligands
such as Chiraphos,4 Norphos,5 BPPM,6 BDPP,7
BINAP,8 Duphos,9 BICP,10 P-Phos, etc.11 However,
many effective phosphine ligands are quite difficult to
prepare and the search for easily prepared new chiral
ligands with high effectiveness is still of high interest.
Chiral organophosphorus ligands play an important
role in metal-catalyzed asymmetric reactions. The sem-
inal work by Knowles and Sabacky in 1968 on the
application of a rhodium chiral phosphine catalyst in
asymmetric hydrogenation essentially started a new era
of study of asymmetric catalysis.1 In 1971, Kagan and
co-workers reported the synthesis of DIOP, the first
chiral bisphosphine ligand and its application in the Rh-
catalyzed asymmetric hydrogenation.2 Prompted by this
development, Knowles et al. further developed their
original monodentate phosphine ligand PAMP (phenyl-
anisylmethylphosphine) to a C2-symmetric chelating
bisphosphine ligand DIPAMP and used it in industrial
scale asymmetric hydrogenation for the commercial
In recent years, new series of phosphorus ligands such as
phosphinite,12 phosphite,13 phosphonite,14 and phosp-
horoamidite,15 have been shown to have high efficiency
in catalytic asymmetric reactions. Chiral phosphinites
can be easily prepared in high yields through the reac-
tion of the corresponding alcohols with chlorophos-
phines in the presence of an organic base. Mixed chiral
phosphorus ligands have also been found to have unique
properties in asymmetric catalytic reactions. For exam-
ple, (R,S)-BINAPHOS, a chiral phosphine–phosphite
ligand derived from BINOL, is highly effective in the
rhodium-catalyzed asymmetric hydroformylations of
prochiral olefins.16
production of L-dopa. Following these important con-
tributions, synthetic organic chemists from around the
world have developed thousands of chiral phosphorus
ligands with diverse structures and have used them in
* Corresponding authors. Tel.: +852-27665607; fax: +852-23649932;
e-mail: bcachan@polyu.edu.hk
Asubclass of chiral ligands derived from ferrocene have
been found to be very effective in many transition-metal-
University Grants Committee Area of Excellence Scheme (Hong
Kong).
0957-4166/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.05.046

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X. Jia et al. / Tetrahedron: Asymmetry 15 (2004) 2273–2278
N
OPAr2
PPh2
O
O
O
O
O
P
P
Fe
PPh2
Fe
PPh2
Fe
1a Ar = C6H5
1b Ar = 3,5-(CF3)2C6H3
2
3
Figure 1. The structures of new chiral ligands derived from ferrocene.
catalyzed asymmetric reactions.17 Hayashi and co-
workers prepared a series of chiral ferrocenylphosphine
ligands starting from Ugi’s chiral a-dimethyl amino-
ethylferrocene and successfully used them in the asym-
metric hydrosilylation, hydrogenation, and Grignard
cross coupling.18 Togni et al. have developed a series of
highly effective bisphosphanes, as exemplified by Josi-
phos, which was used in the Rh-catalyzed asymmetric
hydrogenation on an industrial scale as well as in Pd-
catalyzed allylic alkylation.19 Kagan and co-workers
investigated some ferrocene-based 1,3-bis(phosphanes)
with planar chirality for hydrogenation, with up to 98%
ee being observed.20 Heller and co-workers obtained
high ee’s in the asymmetric hydrogenation of b-aryl-
substituted b-acylaminoacrylates using Et-FerroTANE
as a ligand.21 Knochel and co-workers prepared a
number of ferrocenyl ligands with two phosphanyl
substituents and successfully used them in hydrogena-
tion and Pd(0)-catalyzed allylic substitution reactions.22
Spindler and co-workers described a ligand family based
on the phenylferrocenylethyl backbone and achieved up
to 95% ee in the hydrogenation of a 2-isopropylcinnamic
acid derivative to give a product of high industrial
interest.23 Recently, Boaz et al. reported the preparation
of phosphinoferrocenylaminophosphines and the appli-
cation of them in the rhodium-catalyzed asymmetric
hydrogenation.24
2. Results and discussion
The chiral phosphine–phosphinites ligands can be con-
veniently prepared from Ugi’s amine, N,N-dimethyl-1-
ferrocenylethylamine (Scheme 1). Amine 4 can be
readily converted to phosphine 5 using sec-butyl lithium
instead of the n-butyl lithium with the yield of the
product increasing from 60% to over 80%. Phosphine 5
was reacted with acetic anhydride at 100 ꢁC for 3 h to
afford the acetate with retention of configuration, which
was then reduced with LiAlH4 to give the corresponding
alcohol 6 in 90% yield. The reaction of 6 with a suitable
chlorophosphine in the presence of DMAP and trieth-
ylamine afforded ligands 1a or 1b.
In order to exploit the unique properties of a binaphthyl
moiety, two new chiral ligands (2 and 3) were then
synthesized using synthetic procedures similar to that
for ligand 1. The reaction of the acetate intermediate
1. Ac2O, 100 o
C
N(CH3)2
PPh2
NHCH3
PPh2
Fe
Fe
2. NH2CH3.HCl
5
7
One of the targets in our study of catalytic asymmetric
synthesis is the development of effective chiral ligands
that can be easily prepared and successfully applied in
asymmetric synthesis. Herein we report the synthesis of
new mixed chiral phosphine–phosphinites, phosphine–
phosphoramidite ligands, and phosphine–phosphite 1,
2, and 3, respectively, based on a ferrocene framework
(Fig. 1). The results of using these ligands in the asym-
metric hydrogenation of dehydroamino acids and ena-
mides are also discussed.
O
O
Cl P
N
O
O
P
PPh2
Fe
NEt3
2
Scheme 2. The synthetic route of chiral phosphine–phosphoramidite
ligand 2.
1. Ac2O, 100 o
C
sec-BuLi/ClPPh2
N(CH3)2
N(CH3)2
PPh2
Fe
Fe
2. LiAlH4
5
4
ClPAr2 / NE t
OH
PPh2
3
OPAr2
PPh2
Fe
Fe
6
1a Ar = C6H5
1b Ar = 3,5-(CF3)2C6H3
Scheme 1. The synthetic route for chiral phosphine–phosphinite ligands 1a and 1b.

X. Jia et al. / Tetrahedron: Asymmetry 15 (2004) 2273–2278
2275
O
Cl P
O
O
O
O
OH
PPh2
P
PPh2
Fe
Fe
NEt3
6
3
Scheme 3. The synthetic route of chiral phosphine–phosphinite ligand 3.
Table 1. The asymmetric hydrogenation of a-dehydroamino acid derivatives catalyzed by Rh-1a and Rh-1ba
COOCH3
NHR
COOCH3
L* / Rh
H2
∗
Ar
8a-j
Ar
NHR
Entry
Ligand
Substrate
Solvent
T (ꢁC)
Ee (%)b
1
1a
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
8a
8a
8a
8a
8a
8a
8a
8b
8c
8d
8e
8f
Ar ¼ Ph, R ¼ A
Ar ¼ Ph, R ¼ A
Ar ¼ Ph, R ¼ Ac
Ar ¼ Ph, R ¼ Ac
Ar ¼ Ph, R ¼ Ac
Ar ¼ Ph, R ¼ Ac
Ar ¼ Ph, R ¼ Ac
c
c
2Cl2
2Cl2
CH
CH
rt
rt
rt
rt
rt
rt
5
59.4
86.3
79.6
20.0
90.0
67.9
96.5
99.0
97.0
97.8
96.1
99.1
95.3
95.8
98.3
99.6
2
3
THF
MeOH
4
5
Toluene+CH2Cl2
i-PrOH
6
7
Toluene+CH2Cl2
Toluene+CH2Cl2
Toluene+CH2Cl2
Toluene+CH2Cl2
Toluene+CH2Cl2
Toluene+CH2Cl2
Toluene+CH2Cl2
Toluene+CH2Cl2
Toluene+CH2Cl2
Toluene+CH2Cl2
8
Ar ¼ p-CF3–Ph, R ¼ Ac
Ar ¼ p-Cl–Ph, R ¼ Ac
Ar ¼ p-MeO–Ph, R ¼ Ac
Ar ¼ m-Cl–Ph, R ¼ Ac
Ar ¼ p-Br–Ph, R ¼ Ac
Ar ¼ p-Me–Ph, R ¼ Ac
Ar ¼ H, R ¼ Ac
5
9
5
10
11
12
13
14
15
16
5
5
5
8g
8h
8i
5
5
Ar ¼ p-F–Ph, R ¼ benzoyl
Ar ¼ p-Cl–Ph, R ¼ benzoyl
5
8j
5
a The catalyst was prepared in situ. Hydrogen pressure was 150 psi in all reactions; substrate/catalyst (mol/mol) ¼ 100.
b The ee values were determined by GC analysis using a Chrompack chiral fused silica 25 m · 0.25 mm chirasil-
(S)-configuration based on the comparison with published data.
L-VAL column. All products were in
with the methylammonium chloride led to the secondary
amines 7. Reaction of 7 or 6 with chlorobinaphthoxy-
phosphine afforded ligands 2 or 3, respectively (Schemes
2 and 3).
substrates tested gave over 95% ee (entries 9–16) with
the highest ee being 99.6% (entry 16).
Ligand 1b, with two CF3 groups at the 3 and 5 positions
of the phenyl, afford excellent results in comparison to
those obtained using 1a as the ligand in asymmetric
hydrogenation reactions. This positive result can be
explained as a consequence of the meta-dialkyl effect,
which widely exists in Ru, Pd, Rh, and Ir chemistry. 3,5-
Dialkylphenyl groups used as P-substituents increase the
rigidity of the chiral pocket, with the ee values increased
as a result.25–28
Ligands 1a and 1b were first examined in the Rh-cata-
lyzed asymmetric hydrogenation of (Z)-2-acetamido-
cinnamic acid methyl ester. Common factors governing
the enantioselectivities of the reaction were examined.
The results shown in Table 1 clearly indicate that the
enantioselectivity of the catalyst containing 1b is sub-
stantially better to the catalyst containing 1a. The
enantioselectivity was sensitive to the choice of solvents;
a mixed solvent of dichloromethane and toluene was
found to give the best result. The reaction temperature
was also an important factor. Asignificant increase in
enantioselectivity was observed at lower reaction tem-
peratures. When the reaction temperature was lowered
to 5 ꢁC from ambient temperature, the ee value was
found to increase from 90% to 96.5% (entry 7 vs 5). On
the other hand, hydrogen pressure had relatively little
effect on the enantioselectivity. The use of 1b in the Rh-
catalyzed hydrogenation of the methyl ester of other a-
acylamidocinnamic acids was further studied. All of the
The new phosphine–phosphoramidite ligand 2 and
phosphine–phosphinites 3 were also tested in the rho-
dium-catalyzed asymmetric hydrogenation of a-dehyd-
roamino acid derivatives. The results of the asymmetric
hydrogenation of (Z)-2-acetamidocinnamic acid methyl
ester catalyzed by Rh-2 and Rh-3 complexes under dif-
ferent conditions are summarized in Table 2. Chiral
ligand 2 was found to give remarkable enantioselectivity
in this reaction. An excellent ee value of the desired
product was obtained at room temperature with THF as
solvent. It is noteworthy that the enantioselectivity of

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X. Jia et al. / Tetrahedron: Asymmetry 15 (2004) 2273–2278
Table 2. The asymmetric hydrogenation of a-dehydroamino acid derivatives catalyzed by Rh-2 or Rh-3a
COOCH3
NHR
COOCH3
L* / Rh
H2, r.t.
∗
Ar
Ar
NHR
Entry
Ligand
Substrate
Pressure (psi)
Solvent
Ee (%)b
1
3
3
2
2
2
2
2
2
2
2
2
2
Ar ¼ Ph, R ¼ CH3CO
Ar ¼ Ph, R ¼ CH3CO
Ar ¼ Ph, R ¼ CH3CO
Ar ¼ Ph, R ¼ CH3CO
Ar ¼ Ph, R ¼ CH3CO
Ar ¼ Ph, R ¼ CH3CO
Ar ¼ Ph, R ¼ CH3CO
300
300
300
300
200
300
500
300
300
300
300
300
CH2Cl2
THF
85
89
2
3
CH2Cl2
CH3OH
THF
96
87
4
5
98
99
6
THF
THF
7
99
8
Ar ¼ p-NO2–Ph, R ¼ CH3CO
Ar ¼ p-CH3–Ph, R ¼ CH3CO
Ar ¼ p-F–Ph, R ¼ PhCO
THF
THF
99.6
97.4
99
9
10
11
12
THF
THF
THF
Ar ¼ p-Br–Ph, R ¼ CH3CO
Ar ¼ p-Cl–Ph, R ¼ PhCO
99
99
a The catalyst was prepared in situ. All reactions were carried out at room temperature; substrate/catalyst (mol/mol) ¼ 100.
b The ee values were determined by GC with a Chrompack chiral fused silica 25 m · 0.25 mm chirasil-
(S)-configuration based on the comparison with published data.
L-VAL column. All products were in
Table 3. The enantioselective hydrogenation of enamides catalyzed by Rh-1 and Rh-2 complexa
∗
L* / Rh
Ar
NHCOCH3
Ar
Aryl
NHCOCH3
H2
Entry
Ligand
Solvent
Temperature (ꢁC)
Ee (%)b
1
2
3
4
5
6
7
1a
1b
1b
2
Ph
Ph
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
rt
rt
0
72
83
p-CF3–Ph
91
73
Ph
Ph
Ph
Ph
rt
rt
rt
0
2
77
76
2
i-PrOH
THF
2
87.5
a The catalyst was prepared in situ. Hydrogen pressure was 300 psi in all reactions. All the reactions were carried out at room temperature; substrate/
catalyst (mol/mol) ¼ 100.
b The ee values were determined by GC analysis with a Chrompack chiral fused silica 25 m · 0.25 mm chirasil-
(S)-configuration based on the comparison with published data.
L-VAL column. All products were in
the catalyst is sensitive to the solvent used. Higher ee
values of the products were achieved in THF (99% ee)
while only 87% ee was observed when methanol was
used as solvent (entry 4). In contrast, the hydrogen
pressure had very little effect on the enantioselectivities
(Table 2, entries 5–7).
It is well known that the drawback of chiral phosphinite
ligands is their moisture-sensitivity. In our experiment,
we found that chiral ligands 1b were relatively air and
water stable when compared to other chiral phosphinite
ligands.3;12c The ease of preparation, high enantioselec-
tivity and relative air and water stabilities make the
mixed chiral phosphorus ligands extensively useful in
asymmetric synthesis.
Avariety of ( Z)-2-acetamido-3-arylacrylic acids were
hydrogenated using the Rh-2 catalyst and in all cases the
desired products were found to have 99% ee or higher,
except for the product from the hydrogenation of (Z)-
2-acetamido-3-[(o-methyl)-phenyl]-acrylic acid methyl
ester having an electron donor group on the phenyl ring.
Again, these results compared favorably with those
obtained with the best known chiral phosphine, phos-
phinite, phosphite, phosphonite or phosphoroamidite-
rhodium catalysts.
3. Conclusion
In conclusion, new chiral phosphine–phosphinite,
phosphine–phosphoramidite ligands, and phosphine–
phosphite 1a, 1b, 2, and 3 have been synthesized and
examined for the enantioselective hydrogenation of
dehydroamino acid derivatives and a-aryl enamides.
The results demonstrated that both Rh-1b and Rh-2
complexes are highly efficient catalysts in asymmetric
hydrogenation reactions.
The asymmetric catalytic hydrogenation of enamides
with Rh-1 and Rh-2 were also tested with the results
summarized in Table 3. Moderate to good enantio-
selectivities were obtained.

X. Jia et al. / Tetrahedron: Asymmetry 15 (2004) 2273–2278
2277
4. Experimental
4.4. Preparation of chiral ligand 2
4.1. General handling and materials
Phosphorus trichloride (0.1 mL, 1.1 mmol) and trieth-
ylamine (0.4 mL, 2.9 mmol) were transferred via a syr-
inge into a 100 mL round-bottomed flask containing
(R)-BINOL (0.3 g, 1.0 mmol) in toluene (20 mL) at 0 ꢁC
under a nitrogen atmosphere. After the mixture had
been stirred for 6 h, the volatiles were removed under
vacuum. Asolution of amine 7 (1.0 mmol) and trieth-
ylamine (0.3 mL, 2.1 mmol) in toluene (15 mL) was
added to the flask and the mixture allowed to react
overnight. The resulting mixture was purified through a
pre-dried neutral Al2O3-packed column with toluene as
an eluent. The eluates were concentrated in vacuo to
afford the solid phosphoramidite product (0.61 g, 81%
yield). 1H NMR (500 MHz, CDCl3): d 7.95–7.10 (m,
22H), 6.75–6.73 (d, 1H, J ¼ 8:5 Hz), 5.36–5.30 (m, 1H),
4.44 (s, 1H), 4.31 (s, 1H), 3.98 (s, 5H), 3.89 (s, 1H), 1.74–
1.73 (d, 3H), 1.69 (s, 3H). 13C NMR (125 MHz, CDCl3):
d 150.6, 150.6, 149.6, 140.7, 140.6, 138.5, 138.4, 137.9,
135.8, 135.6, 132.6, 132.7, 132.6, 132.2, 132.0, 131.2,
130.6, 129.8, 129.7, 129.2, 129.104, 128.3, 128.3, 128.2,
128.1, 128.0, 127.9, 127.8, 127.5, 127.0, 127.0, 125.8,
125.8, 125.4, 124.5, 124.3, 123.7, 123.7, 122.9, 122.3,
121.9, 94.8, 94.6, 94.6, 94.4, 75.6, 75.5, 72.0, 51.1, 50.7,
24.7, 18.8. 31P NMR (200 MHz, CDCl3): d 149.5 (d,
J ¼ 53:2 Hz), )23.7 (d, J ¼ 53:2 Hz). HRMS (EI) m=z
All manipulations were carried out under a dry nitro-
gen atmosphere using standard Schlenk techniques or
in a nitrogen atmosphere glove-box unless otherwise
stated. All solvents were distilled and degassed prior to
use.
4.2. Preparation of chiral ligand 1a
Asolution of triethylamine (0.29 mL, 2.1 mmol) and
diphenylphosphinous chloride (0.25 g, 1.1 mmol) in tol-
uene (5 mL) was transferred via a syringe into a 100 mL
round-bottomed flask containing compound (1R,2S)-6
(0.41 g, 1.0 mmol) and DMAP (20 mg) in toluene
(15 mL) at 0 ꢁC under a nitrogen atmosphere. After the
mixture has been stirred 6 h, the resulting mixture was
purified through a Al2O3-packed column with toluene as
an eluent. The eluates were concentrated in vacuo to
afford the solid phosphoramidite (0.19 g, 31% yield).1 H
NMR (500 MHz, CDCl3): d 7.79–7.13 (m, 20H), 5.05–
5.03 (m, 1H), 4.73 (s, 1H), 4.34 (s, 1H), 4.01 (s, 5H), 3.72
(s, 1H), 1.64 (d, 3H, J ¼ 7:0 Hz). 13C NMR (125 MHz,
CDCl3): d 145.3, 144.9, 144.3, 144.1, 139.2, 138.1, 137.9,
135.4, 135.1, 132.2, 131.8, 131.6, 131.0, 129.1, 128.2,
127.5, 125.4, 124.3, 123.2, 122.1, 121.9, 94.4, 94.2,
94.2, 94.1, 76.5, 76.4, 73.1, 52.5, 51.7, 18.7. 31P
NMR (200 MHz, CDCl3): d 37.6, )20.8. HRMS (EI)
m=z calcd for C36H32FeOP2 (Mþ) 598.1278, found
598.1269.
calcd for C45H37FeNO2P2 (Mþ) 741.1649, found
20
741.1668. ½aꢀ ¼ ꢁ208 (c 0.48, toluene).
D
4.5. Preparation of chiral ligand 3
With the same procedure as the preparation of ligand 2
except using alcohol (1R,2S)-6 as reactant 0.29 g (40%
yield) of the solid product was obtained. 1H NMR
(500 MHz, CDCl3): d 8.20–6.90 (m, 22H), 5.45 (m, 1H),
4.42 (s, 1H), 4.25 (s, 1H), 3.99 (s, 5H), 3.92 (s, 1H), 1.81
(d, 3H, J ¼ 7:0Hz). 13C NMR (125 MHz, CDCl3): d
150.4, 150.4, 149.4, 141.3, 141.2, 138.7, 138.6, 137.9,
135.7, 135.7, 132.4, 132.3, 132.3, 132.0, 131.9, 130.9,
130.2, 129.4, 129.1, 128.9, 128.7, 127.9, 127.9, 127.6,
127.4, 127.3, 126.9, 125.6, 125.6, 124.3, 123.7, 122.7,
122.1, 94.8, 94.7, 94.6, 94.5, 76.2, 76.1, 72.2, 51.3, 50.9,
19.6. 31P NMR (200 MHz, CDCl3): d 151.5, )21.3.
HRMS (EI) m=z calcd for C44H34FeO3P2 (Mþ)
728.1333, found 728.1325.
4.3. Preparation of chiral ligand 1b
Triethylamine (0.29 mL, 2.1 mmol) and bis-[3,5-bis-(tri-
fluoromethyl)phenyl]phosphinous chloride (0.5 g, 1.0
mmol) in toluene (5 mL) were transferred via a syringe
into a 100 mL round-bottomed flask containing alcohol
(1R,2S)-6 (0.41 g, 1.0 mmol) and DMAP (20 mg) in
toluene (15 mL) at 0 ꢁC under a nitrogen atmosphere.
After the mixture had been stirred for 6 h, the resulting
mixture was purified through a pre-dried neutral Al2O3-
packed column with toluene as an eluent. The eluates
were concentrated in vacuo to afford the solid phos-
1
phoramidite (0.69 g, 79% yield). H NMR (500 MHz,
CDCl3): d 7.96–6.88 (m, 16H), 5.81 (m, 1H), 4.77 (s,
1H), 4.56 (s, 1H), 4.15 (s, 1H), 4.02 (s, 5H), 1.81 (d, 3H,
J ¼ 2:5 Hz), 1.79 (d, 3H, J ¼ 7 Hz). 13C NMR
(125 MHz, CDCl3): d 146.5, 146.2, 145.0, 144.9, 139.3,
139.2, 138.0, 137.9, 137.9, 135.5, 135.4, 132.2, 132.1,
131.9, 131.9, 131.7, 131.6, 131.5, 131.5, 131.3, 131.2,
129.7, 129.4, 129.2, 128.4, 128.3, 128.2, 127.7, 127.7,
127.6, 125.4, 124.4, 124.3, 123.4, 123.2, 123.2, 122.2,
122.2, 94.3, 94.2, 94.0, 94.0, 76.6, 76.5, 76.4, 76.3, 72.6,
72.6, 70.58, 70.5, 70.0, 69.9, 69.2, 69.2, 22.4, 22.3,
21.5. 31P NMR (200 MHz, CDCl3): d 96.49 (d,
J ¼ 26:0 Hz), )25.21 (d, J ¼ 26 Hz). HRMS (EI) m=z
calcd for C40H28F12FeOP2 (Mþ) 870.0773, found
870.0794.
4.6. A typical procedure for the hydrogenation of
enamides
The catalyst was made in situ by mixing
[Rh(COD)2]BF4 (2.0 mg, 0.005 mmol) and ligand 1b
(5.0 mg, 5.5 lmol) in THF (1 mL) for 10 min. Asmall
portion of the catalyst solution (0.2 mL) was transferred
into a 50 mL glass-lined stainless steel autoclave, which
contained an enamide substrate (0.1 mmol) and a mag-
netic stirring bar. The reactor was charged with hydro-
gen gas and the solution stirred at the required
temperature for a predetermined period of time. After
the reaction was complete, the hydrogen gas was
released and the ee value of the product determined by

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Y. G.; Tang, W.; Wang, W. B.; Li, W.; Zhang, X. J. Am.
Chem. Soc. 2002, 124, 4952.
13. (a) Reetz, M. T.; Neugebauer, T. Angew. Chem., Int. Ed.
1999, 38, 179; (b) Reetz, M. T.; Mehler, G. Angew. Chem.,
Int. Ed. 2000, 39, 3889.
GC analysis with a Chrompack chiral fused silica
25 m · 0.25 mm chirasil- -VAL column.
L
Acknowledgements
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We thank University Grants Committee of Hong Kong
(Areas of Excellence Scheme, AOE P/10-01), Hong
Kong Research Grants Council (Project No: polyu
5185/00P) and the Hong Kong Polytechnic University
Area of Strategic Development Fund for financial
support of this study.
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