New unsymmetrical hybrid ferrocenylphosphine-phosphoramidite ligands derived from H8-BINOL for highly efficient Rh-catalyzed enantioselective hydrogenation

Article abstract of DOI:10.1016/j.tetasy.2005.02.003

A series of new H₈-BINOL-derived unsymmetrical hybrid ferrocenylphosphine-phosphoramidite ligands have been synthesized and successfully used in Rh-catalyzed asymmetric hydrogenations. The same or higher enantioselectivities (99.9% ee) were achieved in the hydrogenation of dimethyl itaconate and α-dehydroamino acid esters as those obtained with BINOL-derived analogues. However, slightly lower enantioselectivities (99.0% ee) were obtained in the hydrogenation of enamides.

Full text of DOI:10.1016/j.tetasy.2005.02.003

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 1233–1238
New unsymmetrical hybrid ferrocenylphosphine-phosphoramidite
ligands derived from H -BINOL for highly efficient
8
Rh-catalyzed enantioselective hydrogenation
a,b
a,b
Qing-Heng Zeng, Xiang-Ping Hu, Zheng-Chao Duan,
a
a
Xin-Miao Liang and Zhuo Zheng
a,
*
a
Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
b
Graduate School of Chinese Academy of Sciences, Beijing100039, China
Received 10 January 2005; accepted 2 February 2005
8
Abstract—A series of new H -BINOL-derived unsymmetrical hybrid ferrocenylphosphine-phosphoramidite ligands have been syn-
thesized and successfully used in Rh-catalyzed asymmetric hydrogenations. The same or higher enantioselectivities (99.9% ee) were
achieved in the hydrogenation of dimethyl itaconate and a-dehydroamino acid esters as those obtained with BINOL-derived ana-
logues. However, slightly lower enantioselectivities (99.0% ee) were obtained in the hydrogenation of enamides.
ꢀ
2005 Elsevier Ltd. All rights reserved.
1
. Introduction
enantioselectivities in the Rh-catalyzed asymmetric
hydrogenation of enamides, dimethyl itaconate and a-
dehydroamino acid derivatives, and that the binaphthyl
moiety was able to play a crucial role in the enantiose-
lectivity and control of the chirality of the hydrogena-
tion products. Therefore, replacing the binaphthyl
Catalytic asymmetric hydrogenation is one of the most
powerful tools for obtaining a wide range of enantio-
merically pure or enriched compounds. Many histori-
cally successful ligands used in this reaction are
1
bidentate P-chelate ligands, and most have a C -sym-
2
moiety with other groups, such as H -binaphthyl, may
8
metrical structure or at least two closely related binding
2
have an important influence on the catalytic activity
and selectivity. Despite the chiral binaphthyl framework
sites. Therefore, C -symmetry remains a popular princi-
2
5
ple for ligand design. However, some recent reports have
demonstrated the potential of unsymmetrical bidentate
phosphorus ligands in the catalytic asymmetric hydroge-
being extensively used in asymmetric catalysis, the par-
tially hydrogenated binaphthyl framework (such as H8-
binaphthyl) has not yet attained the same popularity as
6
nation, challenging the need for C -symmetry in asym-
2
its parent binaphthyl structure in asymmetric catalysis.
3
metric hydrogenation ligand design. For example,
In a few cases, the partially hydrogenated binaphthyl
framework has shown improved chiral induction over
its parent structure due to the increased steric interac-
tion between the two partially hydrogenated naphthal-
Hoge et al. reported that a three-hindered quadrant
motif of Rh-catalysts derived from tert-butyl-
methylphosphino-di-tert-butylphosphinomethane can
provide enantioselectivities equal to the current state
ene rings in H -binaphthyl. Stimulated by our recent
8
of the art with C -symmetrical ligands during asymmetric
2
success in the development of efficient unsymmetrical
hybrid ligands and the effectiveness of the octahydrobi-
naphthyl backbone in asymmetric catalysis, we wished
to develop some new unsymmetrical hybrid phosphine-
4
a
hydrogenation. Recently, we and Chan and co-work-
4
b
ers independently reported that the unsymmetrical
hybrid phosphine-phosphoramidite ligands (S ,R ,S )-1
c
p
a
combining a planar-chiral ferrocene backbone with an
axial-chiral binaphthyl moiety displayed excellent
phosphoramidite ligands based on H -BINOL for the
8
Rh-catalyzed asymmetric hydrogenation. As a result,
we herein report a series of new H -BINOL-derived ferro-
8
cenylphosphine-phosphoramidite ligands (S ,R ,S )-
p
c
a
*
Corresponding author. Tel.: +86 411 84669077; fax: +86 411
4684746; e-mail: zhengz@dicp.ac.cn
2a–c and (R ,S ,S )-2d, exhibiting the same or
c p a
higher enantioselectivity in the hydrogenation of
8
0
957-4166/$ - see front matter ꢀ 2005Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2005.02.003

1234
Q.-H. Zenget al. / Tetrahedron: Asymmetry 16 (2005) 1233–1238
PPh
2
O
O
PPh
2
O
O
N
O
O
N
P
N P
P
R
PPh
2
Fe
Fe
Fe
(
S ,R ,S )-1
(S ,R ,S )-2a: R = Me;
c p a
c
p
a
(
R ,S ,S )-2d
c p a
(
(
S ,R ,S )-2b: R = H;
c p a
S ,R ,S )-2c: R = Et
c
p a
a-dehydroamino acid derivatives and dimethyl itaconate
in comparison with its BINOL-derived parent ligands.
(Z)-acetamidocinnamate 5a by using 1.1 equiv of H8-
BINOL-derived ligand (S ,R ,S )-2a to Rh, while the
corresponding BINOL-derived ligand (S ,R ,S )-1 only
c
p
a
c
p
a
gave the hydrogenation product in 97.6% ee under the
same hydrogenation conditions (entry 1 vs entry 3).
The reaction was not solvent dependent and proceeded
smoothly in all of the solvents tested to give the product
2
. Results and discussions
2.1. Synthesis of H -BINOL-derived ferrocenylphos-
phine-phosphoramidite ligands 2
8
with >99% ee (entries 4 and 5). Lowering the H pres-
2
sure to 1 bar, gave similar enantioselectivities (entry 6).
Other listed ligands were also used in this reaction to
examine the substitutent effect in the enantioselectivity,
and the results showed that there are no substantial dif-
ferences between (S ,R ,S )-2b and (S ,R , S )-2c with
The synthesis of these unsymmetrical hybrid phosphine-
phosphoramidite ligands is straightforward. By the reac-
7
tion of ferrocenylphosphine-amines (S ,R )-3a–c with
c
p
8
H -BINOL-derived (S )-chlorophosphite 4 in toluene
a
8
c
p
a
c
p
a
at 0 ꢁC to rt, ligands (S ,R ,S )-2a–c were easily pre-
(S ,R ,S )-2a, indicated few influence of the substitutent
c p a
c
p
a
pared in 76.9–83.4% yields, as outlined in Scheme 1.
In the same procedure, ligand (R ,S ,S )-2d was synthe-
in amino moiety in the enantioselective induction of
ligands (entries 7 and 8 vs entry 3). However,
(R ,S ,S )-2d only gave a hydrogenation product with
c
p
a
sized from the corresponding (R ,S )-3a in 81.3% yields.
c
p
c
p
a
Similar to its BINOL analogue (S ,R ,S )-1, ligand
c
50.0% ee with the same configuration as that obtained
with (S ,R ,S )-2a, suggesting that a (S )-central chiral-
p
a
(
S ,R ,S )-2a also exhibits an extraordinary stability to-
a
c
p
c
p
a
c
wards air and moisture, and tolerance of various hydro-
genation conditions, which make this ligand highly
practical for general laboratory preparations as well as
scale-up operations.
ity, (R )-planar chirality and (S )-axial chirality were
p a
matched configurations in these H -BINOL-derived
8
phosphine-phosphoramidites for asymmetric hydroge-
nation (entry 9). Considering the relatively simple prep-
aration of (S ,R ,S )-2a, we then selected (S ,R ,S )-2a
c
p
a
c
p
a
2
roamino acid derivatives 5
.2. Rh-catalyzed asymmetric hydrogenation of a-dehyd-
for further study of this reaction. A variety of a-dehyd-
roamino acid esters were undertaken to examine the effi-
ciency of this catalyst system. The results demonstrate
that the Rh/(S ,R ,S )-2a complex was very efficient
for this type of substrates. Excellent enantioselectivities
were obtained in each case regardless of the electronic
properties of the aryl group on the substrates 5 and all
the substrates were hydrogenated in over 99.5% ee even
at low catalyst loadings (entries 10–16).
In the first set of experiments, we used the Rh-catalyzed
asymmetric hydrogenation of a-dehydroamino acid
derivatives to benchmark the potential of these H8-
BINOL derived phosphine-phosphoramidite ligands
for asymmetric catalysis. Hydrogenation was conducted
c
p
a
at room temperature under an H pressure of 10 bar in
2
the presence of 1 mol% of catalysts prepared in situ
from Rh(COD) BF and 1.1 equiv of chiral ligand, with
full conversions were observed in all cases. As shown in
2.3. Rh-catalyzed asymmetric hydrogenation of dimethyl
itaconate 7
2
4
Table 1, the H -BINOL-derived ligands exhibited higher
8
enantioselectivities than their BINOL analogues. Thus,
excellent enantioselectivity (99.9% ee) were achieved in
the Rh-catalyzed asymmetric hydrogenation of methyl
Similar to its BINOL analogue (S ,R ,S )-1, remarkable
c
enantioselectivities were also obtained in the Rh-cata-
lyzed asymmetric hydrogenation of dimethyl itaconate
p
a
PPh
2
PPh
O
O
2
NHR
o
N P
Toluene, 0 C-rt
4 hours
O
O
2
R
Fe
+
P
Cl
Fe
7
6.9-83.4% yields
(
(
(
S ,R ,S )-2a: R = Me;
c p a
(
(
(
S ,R )-3a: R = Me;
c
p
S ,R ,S )-2b: R = H;
S ,R )-3b: R = H;
c
p a
c
p
(S )-4
a
S ,R ,S )-2c: R = Et
S ,R )-3c: R = Et
c
p a
c
p
8 c p a
Scheme 1. Synthesis of H -BINOL-derived ferrocenylphosphine-phosphoramidite ligands (S ,R ,S )-2a–c.

Q.-H. Zenget al. / Tetrahedron: Asymmetry 16 (2005) 1233–1238
1235
Table 1. Rh-catalyzed asymmetric hydrogenation of a-dehydroamino
acid derivatives 5 using H -BINOL-derived ligands (S ,R ,S )-2a–2c
Table 2. Rh-catalyzed asymmetric hydrogenation of dimethyl itaco-
)-2a–2c and
8
c
p
a
nate
(R
7
using
a
)-2d
H
8
-BINOL-derived ligands (S ,R
c
p
,S
a
a
and (R
c
,S
p
,S
a
)-2d
,S
c p
,S
a
CO R1
2
CO2R1
Rh(COD) BF4 / L*
2
*
*
Rh(COD)
2
BF
4
/ L*
MeO2C
CO Me
2
H
2
, solvent
MeO2C
CO Me
2
NHAc
NHAc
r.t., 24 hours
H
2
, solvent
7
8
R2
R2
r.t., 24 hours
b
Ee (%) config.
c
Entry
Ligand
Solvent
1
2
5
5
5
5
5
5
5
a: R = Me, R = H;
1
2
6
6
6
6
6
6
6
a: R = Me, R = H;
1
2
1
2
(S
(S
(S
(S
(S
(S
(S
(S
c
,R
c
,R
c
,R
c
,R
c
,R
c
,R
c
,R
c
,R
p
,S
p
,S
p
,S
p
,S
p
,S
p
,S
p
,S
p
,S
a
a
a
a
a
a
a
a
)-1
CH
CH
CH
CH
CH
CH
2
2
2
2
2
3
Cl
Cl
Cl
Cl
Cl
2
2
2
2
2
99.9 (S)
99.9 (S)
99.9 (S)
94.0 (S)
19.0 (S)
99.9 (S)
99.3 (S)
b: R = Et, R = H;
1
2
b: R = Et, R = H;
1
2
)-2a
)-2b
)-2c
)-2d
)-2a
)-2a
)-2a
c: R = Me, R = 2-Cl;
1
2
c: R = Me, R = 2-Cl;
b
1
2
3
d: R = Me, R = 4-Cl;
1
2
d: R = Me, R = 4-Cl;
1
2
4
5
6
7
8
e: R = Et, R = 4-Cl;
1
2
e: R = Et, R = 4-Cl;
1
2
f: R = Me, R = 2-MeO;
1
2
f: R = Me, R = 2-MeO;
OH
1
2
g: R = Me, R = 4-MeO
1
2
g: R = Me, R = 4-MeO
Toluene
CH OH
d
b
Entry Ligand
Substrate Solvent [Rh/L] Ee (%)
mol%) config.
3
99.9 (S)
c
(
a
Reactions were performed in the presence of substrate/
Rh(COD) BF /ligand = 100:1:1.1 under 10 bar of H in the indicated
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
(S
(S
(S
(S
(S
(S
(S
(S
c
c
c
c
c
c
c
c
,R
,R
,R
,R
,R
,R
,R
,R
p
,S
p
,S
p
,S
p
,S
p
,S
p
,S
p
,S
p
,S
p
,S
p
,S
p
,S
p
,S
p
,S
p
,S
p
,S
p
,S
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
a
)-1
)-1
5a
5a
CH
CH
CH
CH
2
2
2
3
Cl
Cl
Cl
2
2
2
1/1.1
1/2.2
1/1.1
97.6 (R)
99.0 (R)
99.9 (R)
99.7 (R)
99.5( R)
99.8 (R)
99.8 (R)
99.9 (R)
50.0 (R)
99.7 (R)
99.8 (R)
99.7 (R)
99.5( R)
99.8 (R)
99.7 (R)
2
4
2
solvent at room temperature for 24 h. Full conversions were achieved
in all of the reactions.
b
)-2a 5a
)-2a 5a
)-2a 5a
)-2a 5a
)-2b 5a
)-2c 5a
)-2d 5a
)-2a 5b
)-2a 5c
)-2a 5d
)-2a 5e
)-2a 5f
)-2a 5g
)-2a 5a
b
c
Enantiomeric excesses were determined by GC using a c-DEX-225
capillary (0.25mm · 30 m) column.
The absolute configuration was determined by comparing the GC
OH 1/1.1
Toluene 1/1.1
d
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
3
2
2
2
2
2
2
2
2
2
2
OH 1/1.1
retention times with GC data in the literature.
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
1/1.1
1/1.1
1/1.1
1/1.1
1/1.1
1/1.1
1/1.1
1/1.1
1/1.1
d
2
The reaction was performed under an H pressure of 1 bar.
(R
c
,S
,R
,R
,R
,R
,R
,R
,R
0
1
2
3
4
5(
6
(S
(S
(S
(S
(S
S
c
2
9
.4. Rh-catalyzed asymmetric hydrogenation of enamides
c
c
c
c
c
c
To explore further the utility of these Rh-complexes in
the asymmetric hydrogenation, we then applied ligands
2 in the Rh-catalyzed asymmetric hydrogenation of a-
enamides 9, with the results summarized in Table 3. In
contrast to higher enantioselectivities in the hydrogena-
tion of a-dehydroamino acid esters, H -BINOL-derived
ligands (S ,R ,S )-2a–c exhibited somewhat lower
p
enantioselectivities than their BINOL analogue
S ,R ,S )-1. Thus, Rh/(S ,R ,S )-1 hydrogenated
(S
0.1/0.11 99.8 (R)
a
Reactions were performed in the presence of substrate/
Rh(COD) BF /ligand = 100:1:1.1 under 10 bar of H in the indicated
2
4
2
solvent at room temperature for 24 h. Full conversions were achieved
in all of reactions.
8
c
a
b
c
Enantiomeric excesses were determined by GC using a CP-Chiralsil-
L-Val capillary (0.25mm · 30 m) column.
The absolute configuration was determined by comparing the GC
(
c
p
a
c
p
a
retention times with the GC data in the literature.
d
2
The reaction was performed under an H pressure of 1 bar.
Table 3. Rh-catalyzed asymmetric hydrogenation of a-enamides 9
a
using H
8
-BINOL-derived ligands (S ,R
c
p
,S
a
)-2a–c and (R
c p
,S ,S
a
)-2d
b
Ee (%) config.
c
7
by the use of these new H -BINOL-derived phosphine-
8
Entry Ligand
Substrate Solvent
phosphoramidite ligands, with the results summarized in
Table 2. In all cases, full conversions were obtained.
Among these ligands, (S ,R ,S )-2a and (S ,R ,S )-2b
1
2
3
4
5
6
7
8
9
1
1
1
1
(S
(S
c
,R
,R
p
,S
,S
a
a
)-1 9a
)-2a 9a
CH
CH
2
Cl
Cl
2
2
2
2
2
2
2
2
2
2
2
99.6 (R)
96.7 (R)
96.9 (R)
90.5( R)
59.1 (R)
96.4 (R)
95.5 (R)
96.0 (R)
98.3 (R)
97.1 (R)
99.0 (R)
c
p
2
b
c
p
a
c
p
a
c
(S ,R ,S )-2b 9a
2
CH Cl
p
a
a
showed the highest enantioselectivity, and gave the
hydrogenation product in 99.9% ee (entries 2 and 3 vs
entry 1). However, when ligand (S ,R ,S )-2c was used
(S
c
,R
p
,S
)-2c 9a
2
CH Cl
(R ,S ,S )-2d 9a
c
p
p
p
p
p
p
p
p
p
a
a
a
a
a
a
a
a
a
CH Cl
2
(S
(S
(S
(S
(S
(S
(S
(S
c
,R
,R
,R
,R
,R
,R
,R
,R
,S
,S
,S
,S
,S
,S
,S
,S
)-2b 9b
)-2b 9c
)-2b 9d
)-2b 9e
)-2b 9f
)-2b 9g
)-2b 9a
)-2b 9a
CH
CH
CH
CH
CH
CH
CH
2
2
2
2
2
2
3
Cl
Cl
Cl
Cl
Cl
Cl
c
p
a
in this reaction, an observable decrease in the ee value
of the hydrogenation product to 94.0% was observed
c
c
c
c
c
c
c
(
entry 4). This is probably attributable to the larger ste-
0
1
2
3
ric environment due to the presence of an ethyl group in
the amino moiety. When the unmatched ligand
OH 95.8 (R)
(
R ,S ,S )-2d was used in the reaction, an expectedly
c p a
Toluene 96.1 (R)
low enantioselectivity was achieved (entry 5). Excellent
enantioselectivity was also obtained when the reaction
was performed in CH OH and toluene, indicating that
a
Reactions were performed in the presence of substrate/
Rh(COD) BF /ligand = 100:1:1.1 under 10 bar of H in the indicated
2
4
2
3
solvent at room temperature for 24 h. Full conversions were achieved
in all of reactions.
Enantiomeric excesses were determined by GC using a chiral Select
the reaction was not solvent dependent (entries 6 and
7). The H pressure had little influence in the reactivity
and enantioselectivity. When the reaction was carried
b
c
2
1
000 capillary (0.25mm · 30 m) column.
out under an H pressure of 1 bar, the same enantiose-
2
lectivity (99.9% ee) was obtained (entry 8).
The absolute configuration was determined by comparing the GC
retention times with GC data in the literature.

1236
Q.-H. Zenget al. / Tetrahedron: Asymmetry 16 (2005) 1233–1238
N-(1-phenylethenyl)acetamide 9a in 99.6% ee, while the
corresponding H -BINOL-derived (S ,R ,S )-2a only
gave the hydrogenation product in 96.7% ee (entry 2
vs entry 1). We propose that such a phenomenon prob-
ably results from the larger torsional dihedral angle in
dard Schlenk techniques. Hydrogenations were carried
out in a stainless steel autoclave. Solvents were reagent
grade, dried and distilled before use following the stan-
8
c
p
a
9
dard procedures. (S )-H -BINOL, (S ,R )-3a–c and
a
8
c
p
7
(R ,S )-3a were prepared according to the literature
p
procedure. (S )-Chlorophosphite 4 was synthesized fol-
a
c
8
the H -binaphthyl moiety, which has the negative effect
8
in the asymmetric hydrogenation of enamides. Among
ligands (S ,R ,S )-2a–c, (S ,R , S )-2b showed the high-
est enantioselective induction and gave the hydrogena-
tion product of N-(1-phenylethenyl)acetamide 9a in
lowing a modified method for the corresponding BI-
0
1
NOL analogues. a-Dehydroamino acid esters 5 and
11
c
p
a
c
p
a
enamides 9 were known compounds, which were syn-
thesized according to the literature procedure. Dimethyl
itaconate 7 was purchased from Acros. All other chem-
icals were obtained commercially. Optical rotations were
measured on a JASCO P-1020 high sensitive polari-
9
(
6.9% ee (entries 2–4) while the unmatched ligand
R ,S ,S )-2d only showed low enantioselectivities of
c
p
a
5
9.1% ee (entry 5). We then selected (S ,R ,S )-2b for
c p a
1
13
31
further study of this reaction. A series of substituted
enamides 9b–g were then tested in this reaction, and
all of them were hydrogenated in high enantioselectivity.
The highest ee values of 99.0% were achieved in the
hydrogenation of N-[1-(3-methoxyphenyl)ethenyl]acet-
amide 9g (entries 6–11). However, in all cases, slightly
lower enantioselectivities were observed in comparison
with those obtained with Rh/(S ,R ,S )-1 reported by
meter. H, C and P NMR spectra were recorded on
a BRUKER DEX 400 (400 MHz) spectrometer. Chemical
shifts were determined relative to the residual solvent
peaks. Enantiomeric excesses were determined by capil-
lary GC analysis with a CP-Chiralsil-L-Val column
(0.25mm · 30 m) for 6, c-DEX-225capillary column
(0.25mm · 30 m) for 8, and a chiral Select 1000 column
(0.25mm · 30 m) for 10.
c
p
a
4
a
us recently. When the reaction was carried out in
CH OH or toluene, a slightly lower enantioselectivities
were observed (entries 12 and 13).
4.2. General procedure for the synthesis of H -BINOL-
8
derived ferrocenylphosphine-phosphoramidite ligands 2
3
A suspension of (S )-H -BINOL (1.03 g, 3.5mmol) and
a
8
O
O
1-methyl-2-pyrrolidone (0.001 g, 0.01 mmol) in PCl3
7.21 g, 52.5 mmol) was warmed to 75 ꢁC and then stir-
(
HN
HN
red for 5min. After this time, a clear solution was ob-
tained. The bulk of the excess PCl3 was removed
under reduced pressure and then the final traces were re-
moved by azeotropic distillation with toluene (10 mL) in
vacuo. A white solid corresponding to the title com-
*
2 4
Rh(COD) BF / L*
H
2
(10 bar), solvent
r.t., 24 hours
R
R
9
9
9
9
a: R = H; 9b: R =4-Me;
c: R = 4-Cl; 9d: R = 4-Br;
e: R = 4-CF ; 9f: R = 4-OMe;
10a: R = H; 10b: R =4-Me;
10c: R = 4-Cl; 10d: R = 4-Br;
10e: R = 4-CF ; 10f: R = 4-OMe;
3
3
pound (S )-chlorophosphite 4 was obtained, which can
a
g: R = 3-OMe
10g: R = 3-OMe
be further purified by recrystallization from n-hexane.
The resulting (S )-chlorophosphite 4 (358.5 mg, 1.0
a
mmol) was then dissolved in 4.0 mL of dried toluene,
which was cooled to 0 ꢁC. A solution of (S ,R )-3a–c
3. Conclusion
c
p
or (R ,S )-3a (1.0 mmol) and Et N (303 mg, 3.0 mmol)
c
p
3
In conclusion, we have developed a series of new H8-
BINOL-derived ferrocenylphosphine-phosphoramidite
ligands for highly efficient Rh-catalyzed asymmetric
hydrogenation. In comparison to its BINOL analogues,
the same or higher enantioselectivities in the hydrogena-
tion of dimethyl itaconate and a-dehydroamino acid
derivatives were observed, although, slightly lower
enantioselectivities were achieved in the hydrogenation
of a-enamides. Thus, by the use of ligand (S ,R ,S )-2,
up to 99.9% ee, 99.9% ee and 99.0% ee were obtained
in the hydrogenation of a-dehydroamino acid deriva-
tives, dimethyl itaconate and a-enamides, respectively.
Further investigations of other catalytic asymmetric
in 4.0 mL of toluene was added to above solution for
30 min. The resulting mixture was left standing at room
temperature overnight. The precipitate was filtered, and
the solid washed with toluene (5mL · 1). The filtrate
was collected, and concentrated under reduced pressure.
Adding the n-hexane to the filtrate gave the yellow
powder 2, which was sufficiently pure for further use.
An analytic sample was obtained by column chromato-
graphy purification following recrystallization from n-
hexane/CH Cl to give yellow powder 2 in high yields.
c
p
a
2
2
4.2.1. N-Methyl-N-{(S)-1-[(R)-2-(diphenylphosphino)ferr-
ocenyl]ethyl}-(S)-5,5 ,6,6 ,7,7 ,8,8 -octahydro-1,1 -bi-2-
naphthyl phosphoramidite (S ,R ,S )-2a. The general
0
0
0
0
0
reactions with these H -BINOL-derived phosphine-
8
c
p
a
phosphoramidite ligands are underway and progress will
be reported in due time.
procedure was followed with (S ,R )-3a as starting
c p
material to give a foam solid (S ,R ,S )-2a. Yield:
c
p
a
2
D
5
1
7
(
6.9%. ½aŠ ¼ þ161 (c 0.3, CHCl3);
H
NMR
400 MHz, CDCl ): d 1.49–1.51 (m, 2H), 1.65 (d,
3
4
. Experimental
J = 3.2 Hz, 3H), 1.72–1.78 (m, 9H), 2.14–2.21 (m, 2H),
.50–2.60 (m, 2H), 2.72–2.82 (m, 4H), 3.86 (s, 1H),
3.96 (s, 5H), 4.30 (s, 1H), 4.43 (s, 1H), 5.17–5.21 (m,
H), 6.27–6.29 (m, 1H), 6.77–6.79 (m, 1H), 6.88–6.94
(m, 2H), 7.07–7.11 (m, 2H), 7.17–7.21 (m, 3H), 7.36–
2
4
.1. General
1
All synthetic reactions and manipulations were per-
formed in a nitrogen or argon atmosphere using stan-
1
3
7.37 (m, 3H), 7.56–7.57 (m, 2H); C NMR (400 MHz,

Q.-H. Zenget al. / Tetrahedron: Asymmetry 16 (2005) 1233–1238
1237
CDCl ): d 18.3, 22.1, 22.2, 27.1, 27.2, 28.6, 68.6, 69.2,
4.3. General procedure for asymmetric hydrogenation
3
6
1
9.8, 71.3, 117.7, 118.3, 126.9, 127.2, 127.4, 128.4,
28.5, 131.7, 135.0, 135.2. P NMR (400 MHz, CDCl3):
3
1
In a nitrogen-filled glovebox, a stainless steel autoclave
was charged with Rh(COD) BF
(4.0 mg, 1 ·
10 mmol) and H -BINOL-derived ferrocenylphos-
d 24.9 (d, J = 124 Hz), 142.4 (d, J = 124 Hz). HRMS
2
4
ꢀ
2
calcd for C H FeNO P + H: 750.2353, found:
7
4
5
45
2
2
8
ꢀ
2
50.2337.
phine-phosphoramidite ligands 2 (1.1 · 10 mmol) in
mL of a degassed CH Cl . After stirring for 10 min
1
2
2
4
.2.2. N-{(S)-1-[(R)-2-(Diphenylphosphino)ferrocenyl]-
at room temperature. A substrate (10 mmol) in 1 mL
of the same solvents was added to the reaction mixture,
and then the hydrogenation performed at room temper-
0
0
0
0
0
ethyl}-(S)-5,5 ,6,6 ,7,7 ,8,8 -octahydro-1,1 -bi-2-naphthyl
phosphoramidite (S ,R ,S )-2b. The general procedure
was followed with (S ,R )-3b as starting material to give
c
p
a
ature under an H pressure of 10 bar for 24 h. The reac-
2
c
p
25
a foam solid (S ,R ,S )-2b. Yield: 83.4%. ½aŠ ¼ þ238 (c
tion mixture was passed through a short silica gel
column to remove the catalyst. After evaporating the
solvent, the crude reaction mixture was subjected to
GC to determine the enantiomeric excesses and yields
of hydrogenation products. Enantiomeric excesses were
determined by capillary GC analysis with a CP-Chiral-
sil-L-Val column (0.25mm · 30 m) for 6, c-DEX-225
capillary column (0.25mm · 30 m) for 8, and a chiral
Select 1000 column (0.25mm · 30 m) for 10.
c
p
a
D
1
0
.3, CHCl ); H NMR (400 MHz, CDCl ): d 1.51–1.53
3 3
(
m, 2H), 1.65(d, J = 8.0 Hz, 3H), 1.74–1.77 (m, 6H),
2
4
.19–2.24 (m, 2H), 2.50–2.66 (m, 2H), 2.74–2.81 (m,
H), 3.15–3.21 (m, 1H), 3.83 (s, 1H), 3.96 (s, 5H), 4.25
(
1
(
s, 1H), 4.38 (s, 1H), 4.62–4.68 (m, 1H), 6.46–6.48 (m,
H), 6.73–6.75(m, 1H), 6.92–7.19 (m, 7H), 7.36–7.53
m, 3H), 7.54–7.55 (m, 2H); C NMR (400 MHz,
1
3
CDCl ): d 22.1, 22.3, 25.2, 27.3, 28.7, 68.0, 68.5, 69.2,
3
6
1
9.4, 71.1, 118.1, 118.9, 127.1, 127.5, 127.9, 128.5,
28.6, 131.9, 132.1, 134.8, 135.0, 137.0, 148.1.
3
1
P
NMR (400 MHz, CDCl ): d 23.9, 144.3 (d, J =
3
Acknowledgements
4
7
8.8 Hz). HRMS calcd for C H FeNO P + H:
36.2197, found: 736.2243.
44 43 2 2
The authors would like to thank the National Natural
Science Foundation of China (20472083) for financial
support of this work.
4
.2.3. N-Ethyl-N-{(S)-1-[(R)-2-(diphenylphosphino)ferro-
0
0
0
0
0
cenyl]ethyl}-(S)-5,5 ,6,6 ,7,7 ,8,8 -octahydro-1,1 -bi-2-
naphthyl phosphoramidite (S ,R ,S )-2c. The general
procedure was followed with (S ,R )-3c as starting
c
p
a
c
p
material to give a foam solid (S ,R ,S )-2c. Yield:
c
References
p
a
25
1
7
7.1%. ½aŠ ¼ þ180 (c 0.3, CHCl3);
H
NMR
D
(
400 MHz, CDCl ): d 0.28–0.32 (m, 3H), 1.46–1.48 (m,
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3
2
5
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(
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6
1
3
C NMR (400 MHz, CDCl ): d 16.6, 20.6, 22.3, 27.1,
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1
2
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4
6
47
2 2
7
64.2544.
2
3
4
.2.4. N-Methyl-N-{(R)-1-[(S)-2-(diphenylphosphino)ferr-
0
0
0
0
0
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a
c
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3
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p
a
2
5
1
8
1.3%. ½aŠ ¼ ꢀ254 (c 0.3, CH Cl );
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D
2
2
(
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4
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s, 1H), 5.03–5.05 (m, 1H), 6.68–6.70 (m, 1H), 6.85–
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7
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1
3
2
2
(
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3
6
1
9.3, 69.8, 71.3, 118.3, 126.9, 127.5, 128.1, 128.6,
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1
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4
5
45
2 2
7
50.2353, found: 750.2402.

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