Readily available chiral phosphine-aminophosphine ligands derived from 1-phenylethylamine for Rh-catalyzed enantioselective hydrogenations

Article abstract of DOI:10.1016/j.tetasy.2010.03.008

A series of new chiral phosphine-aminophosphine ligands have been prepared via a two- or three-step transformation from commercially available and inexpensive (S)-1-phenylethylamine, and successfully used in the rhodium-catalyzed asymmetric hydrogenation

Full text of DOI:10.1016/j.tetasy.2010.03.008

Tetrahedron: Asymmetry 21 (2010) 420–424
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Readily available chiral phosphine–aminophosphine ligands derived from
1-phenylethylamine for Rh-catalyzed enantioselective hydrogenations
Xiao-Mao Zhou a, Jia-Di Huang b, Li-Bin Luo a, Cheng-Lu Zhang c, Zhuo Zheng b, Xiang-Ping Hu b,
*
a Institute of Pesticide, Hunan Agricultural University, Changsha 410128, China
b Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
c School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of new chiral phosphine–aminophosphine ligands have been prepared via a two- or three-step
transformation from commercially available and inexpensive (S)-1-phenylethylamine, and successfully
used in the rhodium-catalyzed asymmetric hydrogenation of various enamides, b-dehydroamino acid
esters, and dimethyl itaconate. The results show that the ligand structure plays an important influence
on both the reactivity and enantioselectivity. Ligand 2d bearing a N–H proton and two F-atoms on the
3,5-positions of the phenyl ring of the aminophosphino moiety was most effective for the hydrogenation
of enamides and (Z)-b-aryl-b-(acylamino)acrylates, whereas ligand 1b showed the highest enantioselec-
tivities in the hydrogenation of (Z)-b-alkyl-b-(acylamino)acrylates and dimethyl itaconate.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 6 January 2010
Accepted 8 March 2010
Available online 8 April 2010
1. Introduction
Rh-catalyzed asymmetric hydrogenation of various dimethyl
a
a
-benzoyloxyethenephosphonates
-enamido phosphonates (Fig. 1).
and
N-benzyloxycarbonyl
Catalytic asymmetric hydrogenation is arguably one of the most
powerful and practical ways to access chiral compounds in con-
temporary synthetic chemistry, in which bidentate phosphorus li-
gands have proved to be the most successful.1 In the past, C2
symmetry has been an important principle in developing efficient
bisphosphorus ligands.2 Indeed, a large number of bidentate phos-
phorus ligands with a symmetrical structure such as BINAP,3 Du-
Phos,4 and TangPhos5 have therefore been reported, and many of
them showed good performance in a wide range of asymmetric
hydrogenations. However, this does not mean that C2 symmetry
is essential for ligand design. In fact, the past decade has witnessed
significant advancement in the use of unsymmetrical hybrid biden-
tate phosphorus ligands such as phosphine–phosphoramidite
ligands,6 phosphine–phosphite ligands7, and phosphine–amino-
phosphine ligands8 for catalytic asymmetric hydrogenation. These
types of ligands normally display excellent performance in a vari-
ety of asymmetric hydrogenations, comparable to or even higher
than those obtained with C2-symmetrical ligands. The develop-
ment of novel unsymmetrical hybrid bidentate phosphorus ligands
with properties superior to their predecessors therefore attracts
more attention and remains an interesting task.
H
N
PPh
CH
N
PPh
PPh
2
3
2
2
PPh
2
(S)-1a
(S)-1b
Figure 1. Chiral 1-phenylethylamine-derived phosphine–aminophosphine ligands
(S)-1a and (S)-1b.
Accessibility, modularity, excellent air- and moisture-stability,
and low cost make these ligands highly attractive for practical
use. To further expand upon the utility of this ligand class in cata-
lytic asymmetric hydrogenation, we herein report our detailed
studies on the optimization of this ligand structure and their appli-
cation in the Rh-catalyzed asymmetric hydrogenation of some
functionalized olefins including enamides, b-dehydroamino acid
esters, dimethyl itaconate, and a-dehydroamino acid ester.
2. Results and discussion
2.1. Synthesis of phosphine–aminophosphine ligands 2a–h
In our previous study, we reported on a new class of phosphine–
aminophosphine ligands 1a–b, which were readily prepared from
commercially available and inexpensive (S)-1-phenylethylamine.9
Subsequently, these ligands were found to be very useful in the
As shown in Scheme 1, these new phosphine–aminophosphine
ligands can be easily prepared from (S)-1-phenylethylamine. Ini-
tially, (S)-1-phenylethylamine 3 was subjected to ortho-lithiation,
then trapped with ClPPh2 to afford the key intermediate (S)-4a as
we have reported in a previous paper.9 The treatment of (S)-4a
* Corresponding author. Tel.: +86 411 84379276; fax: +86 411 84684746.
E-mail address: xiangping@dicp.ac.cn (X.-P. Hu).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.03.008

X.-M. Zhou et al. / Tetrahedron: Asymmetry 21 (2010) 420–424
421
R
NH2
NHR
N
ClPAr2, toluene
1) n-BuLi, ClSiMe3, Et2O, 0 o
C
Et3N, 0oC
PAr 2
PPh2
PPh2
2) n-BuLi, ClPPh2, Et2O, -30 o
C
(S)-3
(S)-2a-h
(S)-4a: R = H
(S)-4b: R = Me
1) HCOOEt
2) LiAlH4/THF
F
F3C
CF3
CH3
F
F
CF3
H
H
H
H
N P
N P
N P
N P
PPh2
PPh2
CF3
PPh2
PPh2
F
F3C
CF3
CF3
CH3
CH3
(S)-2a
(S)-2b
(S)-2d
(S)-2c
F3C
F
CF3
CF3
F
F
Me
Me
Me
Me
N P
N P
N P
N P
PPh2
PPh2
PPh2
PPh2
F3C
F
CF3
CH3
(S)-2e
(S)-2f
(S)-2g
(S)-2h
Scheme 1. Synthesis of new chiral phosphine–aminophosphine ligands 2a–h from (S)-1-phenylethylamine.
Table 1
with HCOOC2H5 generated the acylated product, which was
reduced with LiAlH4 in THF to form monomethylated (S)-4b in a
satisfactory yield. The reaction of (S)-4a and (S)-4b with 1.1 equiv
of ClPAr2 in toluene at 0 °C in the presence of Et3N provided the
target phosphine–aminophosphine ligands 2a–h in good yields.
As their parent ligands (S)-1a and (S)-1b, these newly developed
phosphine–aminophosphine ligands (S)-2a–h also show excellent
air- and moisture-stability. They can be held in open air for several
weeks which does not cause any changes in their 31P NMR.
Rh-catalyzed asymmetric hydrogenation of enamides 5 with phosphine–aminophos-
phine ligands 1 and 2a
O
O
[Rh(COD)2]BF4 (1 mol%)
ligand (1.1 mol%)
HN
HN
*
H2 (10 atm)
CH3OH, rt, 24 h
R
R
5
6
ee (%)b (config.)
2.2. Hydrogenation of enamides
Entry
Ligand
Substrate
Conv. (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
(S)-1a
(S)-2a
(S)-2b
(S)-2c
(S)-2d
(S)-1b
(S)-2e
(S)-2f
(S)-2g
(S)-2h
(S)-2d
(S)-2d
(S)-2d
(S)-2d
(S)-2d
(S)-2d
(S)-2d
5a: R = H
5a: R = H
5a: R = H
5a: R = H
5a: R = H
5a: R = H
5a: R = H
5a: R = H
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
78
88.0 (R)
91.7 (R)
81.9 (R)
93.3 (R)
93.7 (R)
79.2 (R)
75.8 (R)
75.7 (R)
74.9 (R)
65.1 (R)
93.7 (R)
93.1 (R)
94.9 (R)
95.1 (R)
93.5 (R)
92.0 (R)
90.6 (R)c
In the first set of experiments, we used the Rh-catalyzed asym-
metric hydrogenation of enamides 5 to benchmark the potential of
these newly developed phosphine–aminophosphine ligands for
asymmetric hydrogenation. Hydrogenation was performed in
CH3OH at room temperature under an H2 pressure of 10 atm in
the presence of 1 mol % of catalysts prepared in situ from
[Rh(COD)2]BF4 and 1.1 equiv of chiral ligand; the results are sum-
marized in Table 1. The results suggest that the substituents on
the phenyl ring of the aminophosphino moiety have some influ-
ence on the enantioselectivity. Ligand (S)-1a without a substituent
on the phenyl ring provided an ee value of 88.0% (entry 1). The
introduction of a 4-CF3 group onto the phenyl ring resulted in an
observable increase in enantioselectivity of 91.7% ee (entry 2).
However, the presence of a 4-CH3 group on the phenyl ring re-
duced the enantioselectivity to 81.9% ee (entry 3). Both ligand 2c
and 2d bearing two substituents on the 3,5-positions of the phenyl
ring gave good enantioselectivities (93.3% ee and 93.7% ee, respec-
tively) (entries 4 and 5).
5a: R = H
5a: R = H
5b: R = 4-Me
5c: R = 4-CF3
5d: R = 4-Cl
5e: R = 4-Br
5f: R = 4-OMe
5g: R = 3-OMe
5a: R = H
a
Hydrogenations were performed in 2 mL of CH3OH with 0.5 mmol of substrate
and 1 mol % of catalyst, prepared in situ from [Rh(COD)2]BF4 and 1.1 equiv of ligand,
at room temperature and at an H2 pressure of 10 atm for 24 h.
b
Conversions and enantiomeric excesses were determined by GC on a chiral
select 1000 column. The absolute configuration was determined by comparing the
GC retention times with GC data in the literature.6g
The substituent on the amino group dramatically affects the
enantioselectivity. Ligands 1a and 2a–d with an N–H proton gave
significantly higher enantioselectivities than those with a methyl
substituent on the amino moiety (entries 1–5 vs entries 6–10). Thus,
ligand 2d with a N–H proton provided an ee value of 93.7% (entry 5),
c
Using 0.1 mol % of catalyst.
whereas the corresponding N-methyl-substituted ligand 2h gave an
ee value of only 65.1% (entry 10). Hydrogenation of a variety of ena-

422
X.-M. Zhou et al. / Tetrahedron: Asymmetry 21 (2010) 420–424
mides was then performed with ligand 2d. The results show that the
present catalytic system was efficient for this type of substrates.
Good enantioselectivities were obtained in each case regardless of
theelectronicpropertiesof thesubstituent onthephenylringof sub-
strates 5, andall substrates were hydrogenated in 92.0–95.1% ee (en-
tries 11–16). However, lowering the catalyst loading to 0.1 mol %
resulted in the incomplete conversion (entry 17).
As shown in Table 3, the ligand structure was also found to be
crucial to catalytic activity and enantioselectivity for the hydroge-
nation of b-alkyl-b-(acylamino)acrylates. However, with the
hydrogenation of enamides and (Z)-b-aryl-b-(acylamino)acrylates,
ligand 1b gave the best result in the hydrogenation of (Z)-b-alkyl-
b-(acylamino)acrylate substrate 9a, in which full conversion and
98.3% ee were obtained (entry 6). Increasing the H2 pressure to
20 atm had no impact on the enantioselectivity (entry 11). Under
these conditions, a series of (Z)-b-alkyl-b-(acylamino)acrylates
9b–d were hydrogenated in full conversions and good to excellent
enantioselectivities (91.2–98.9% ee) (entries 12–14). However, the
present catalytic system is inefficient for the hydrogenation of the
(E)-isomer, giving only low enantioselectivities and incomplete
conversions (entries 15–19). This result is contrary to most of re-
ports2,10 on the hydrogenation of b-(acylamino)acrylates in which
(E)-isomers normally show higher enantioselectivities in catalytic
asymmetric hydrogenation.
2.3. Hydrogenation of b-(acylamino)acrylates
In comparison with the hydrogenation of enamides, the hydro-
genation of b-(acylamino)acrylates is more challenging. Although
many phosphorus-containing ligands have been reported to exhi-
bit good to excellent enantioselectivities in the Rh-catalyzed asym-
metric hydrogenation of b-(acylamino)acrylates over the past few
years,10 for most catalytic systems, high enantioselectivities were
obtained only when (E)-b-(acylamino)acrylates were used as sub-
strates, while the results of hydrogenation of the (Z)-isomers, in
particular (Z)-b-aryl-b-(acylamino)acrylates, are less satisfying.
Stimulated by the success in the hydrogenation of enamides, we
attempted to examine the efficiency of the present catalytic system
in the Rh-catalyzed asymmetric hydrogenation of this more chal-
lenging substrate class, (Z)-b-aryl-b-(acylamino)acrylates 7; and
the results are summarized in Table 2. The results disclosed that
the substituents on the phenyl ring of the aminophosphino group
had significant influence on the catalytic activity and enantioselec-
tivity. Ligand 1a, which showed excellent enantioselectivities in
Table 3
Rh-catalyzed asymmetric hydrogenation of b-alkyl-b-(acylamino)acrylates
9 with
phosphine–aminophosphine ligands 1 and 2a
[Rh(COD)2]BF4 (1 mol%)
NHAc
*
NHAc
ligand (1.1 mol%)
COOR2
COOR2
R1
R1
H2 (10 atm)
THF, rt, 24 h
10
9
the Rh-catalyzed asymmetric hydrogenation of a-enol ester phos-
Entry
Ligand
Substrate (R1, R2)
Conv. (%)
ee (%)b (config.)
phonates, gave very low catalytic activity (entry 1). As observed in
the hydrogenation of enamides, ligand 2d with an N–H proton and
two F-atoms on the 3,5-positions of the phenyl ring of the amin-
ophosphino moiety displayed the best catalytic performance (full
conversion and 89.5% ee) (entry 5). This ligand is also effective
for a variety of (Z)-b-aryl-b-(acylamino)acrylates. In all cases, full
conversions and good enantioselectivities (89.3–91.5% ee) were
achieved (entries 11–15).
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
(S)-1a
(S)-2a
(S)-2b
(S)-2c
(S)-2d
(S)-1b
(S)-2e
(S)-2f
(S)-2g
(S)-2h
(S)-1b
(S)-1b
(S)-1b
(S)-1b
(S)-2e
(S)-2f
(S)-2g
(S)-2h
(S)-1b
(Z)-9a (Me, Me)
(Z)-9a (Me, Me)
(Z)-9a (Me, Me)
(Z)-9a (Me, Me)
(Z)-9a (Me, Me)
(Z)-9a (Me, Me)
(Z)-9a (Me, Me)
(Z)-9a (Me, Me)
(Z)-9a (Me, Me)
(Z)-9a (Me, Me)
(Z)-9a (Me, Me)
(Z)-9b (Me, Et)
(Z)-9c (Et, Me)
(Z)-9d (i-Pr, Me)
(E)-9a (Me, Me)
(E)-9a (Me, Me)
(E)-9a (Me, Me)
(E)-9a (Me, Me)
(E)-9a (Me, Me)
>99
98
16
90
99
>99
69
97
31
15
>99
>99
>99
>99
71
86
65
58
97
94.7 (R)
95.1 (R)
80.1 (R)
94.9 (R)
94.5 (R)
98.3 (R)
93.3 (R)
95.7 (R)
80.3 (R)
80.0 (R)
98.1 (R)c
98.9 (R)c
95.0 (R)c
91.2 (S)c
43.2 (S)
51.7 (S)
28.6 (S)
27.7 (S)
37.0 (S)
Table 2
Rh-catalyzed asymmetric hydrogenation of (Z)-b-aryl-b-(acylamino)acrylates 7 with
ligands 1 and 2a
[Rh(COD)2]BF4 (1 mol%)
NHAc
*
NHAc
COOR
(Z)-7
ligand (1.1 mol%)
COOR
Ar
H2 (10 atm)
THF, rt, 24 h
Ar
8
a
Hydrogenations were performed in 2 mL of THF with 0.5 mmol of substrate and
Entry
Ligand
Substrate (Ar, R)
Conv. (%)
ee (%)b (config.)
1 mol % of catalyst, prepared in situ from [Rh(COD)2]BF4 and 1.1 equiv of ligand, at
room temperature and a H2 pressure of 10 atm for 24 h.
c
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
(S)-1a
(S)-2a
(S)-2b
(S)-2c
(S)-2d
(S)-1b
(S)-2e
(S)-2f
(S)-2g
(S)-2h
(S)-2d
(S)-2d
(S)-2d
(S)-2d
(S)-2d
7a (Ph, Et)
7a (Ph, Et)
7a (Ph, Et)
7a (Ph, Et)
7a (Ph, Et)
7a (Ph, Et)
7a (Ph, Et)
7a (Ph, Et)
7a (Ph, Et)
7a (Ph, Et)
7b (Ph, Me)
7c (4-MeC6H4, Me)
7d (4-MeOC6H4, Me)
7e (4-ClC6H4, Me)
7f (3-MeOC6H4, Me)
<5
>99
>99
>99
>99
98
<5
55
74
93
>99
>99
>99
>99
>99
—
b
Conversions and enantiomeric excesses were determined by GC on a chiral
86.3 (S)
67.5 (S)
87.1 (S)
89.5 (S)
77.5 (S)
select 1000 column. The absolute configuration was determined by comparing the
GC retention times with GC data in the literature.6e
c
Hydrogenation was performed under a H2 pressure of 20 atm.
c
—
2.4. Hydrogenation of dimethyl itaconate and
acid esters
a-dehydroamino
79.5 (S)
70.0 (S)
81.7 (S)
91.1 (S)
89.3 (S)
91.5 (S)
90.5 (S)
90.7 (S)
To explore further the utility of these phosphine–aminophos-
phine ligands in catalytic asymmetric hydrogenation, we then ap-
plied them in the Rh-catalyzed asymmetric hydrogenation of
dimethyl itaconate 11 and
a-dehydroamino acid ester 13, and
a
the results are shown in Table 4. For the hydrogenation of dimethyl
itaconate 11, ligand 1b displayed the best result, in which full con-
version and 95.1% ee were obtained (entry 6). These phosphine–
aminophosphine ligands are inefficient for the hydrogenation of
Hydrogenations were performed in 2 mL of THF with 0.5 mmol of substrate and
1 mol % of catalyst, prepared in situ from [Rh(COD)2]BF4 and 1.1 equiv of ligand, at
room temperature and a H2 pressure of 10 atm for 24 h.
b
Conversions and enantiomeric excesses were determined by GC on a chiral
select 1000 column. The absolute configuration was determined by comparing the
GC retention times with GC data in the literature.6e
a-dehydroamino acid ester 13 in terms of the enantioselectivity
c
(i.e., only low enantioselectivity was achieved).
Not determined because of low conversion.

X.-M. Zhou et al. / Tetrahedron: Asymmetry 21 (2010) 420–424
423
substrates 5,12 (Z)-7,13 9,13 and 1314 were prepared according to
the reported procedure. Dimethyl itaconate 11 was purchased
from Aldrich. All other chemicals are commercially available. The
1H NMR spectra were recorded on a 400 MHz spectrometer. Chem-
ical shifts were reported in ppm from tetramethylsilane with the
solvent resonance as the internal standard (CDCl3, d = 7.26). Data
are reported as follows: chemical shift (ppm), multiplicity (s = sin-
glet, d = doublet, t = triplet, q = quartet, m = multiplet), coupling
constants (Hz), integration, and assignment. 13C NMR data were
collected on a 100 MHz spectrometer with complete proton decou-
pling. Chemical shifts are reported in ppm from the tetramethylsil-
ane with the solvent resonance as internal standard (CDCl3,
d = 77.0). 31P NMR spectra were recorded on a 162 MHz spectrom-
eter. The enantiomeric excesses were determined by chiral GC.
Table 4
Rh-catalyzed asymmetric hydrogenation of dimethyl itaconate 11 and
a-dehydroa-
mino acid ester 13 with phosphine–aminophosphine ligands 1 and 2a
[Rh(COD)2]BF4 (1 mol%)
ligand (1.1 mol%)
COOCH3
COOCH3
COOCH3
H3COOC
H3COOC
H2 (10 atm)
CH2Cl2, rt, 24 h
12
11
[Rh(COD)2]BF4 (1 mol%)
ligand (1.1 mol%)
COOCH3
NHAc
13
H2 (10 atm)
CH3OH, rt, 24 h
NHAc
14
Entry ligand
Substrate 11
Substrate 13
Specific rotations were reported as follows: ½a D25
ꢀ
(c g/100 mL, in
Conv. (%) ee (%)b (config.) Conv. (%) ee (%)b (config.)
solvent).
1
2
3
4
5
6
7
8
9
(S)-1a
(S)-2a
(S)-2b
(S)-2c
>99
>99
>99
>99
49.7 (R)
12.3 (R)
10.9 (S)
84.3 (R)
42.9 (R)
95.1 (R)
89.5 (R)
86.9 (R)
42.5 (R)
90.0 (R)
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
11.4 (S)
25.1 (S)
21.1 (S)
18.6 (S)
21.7 (S)
19.0 (S)
32.8 (S)
41.3 (S)
26.9 (S)
27.8 (S)
4.2. General procedure for the preparation of phosphine–
aminophosphine ligands 2a–h
(S)-2d >99
Amino-phosphine intermediate (S)-DPPNH2 4a (305 mg,
1.0 mmol) was dissolved in 4 mL of dried and degassed toluene,
to which 0.42 mL of triethylamine was added. The mixture was
cooled in an ice-water bath, and then chlorodi(4-trifluorophe-
nyl)phosphine (392 mg, 1.1 mmol, 1.1 equiv) was added dropwise.
The reaction mixture was allowed to warm to ambient tempera-
ture overnight at which point TLC indicated no 4a. After filtrating
off the precipitate, the reaction mixture was concentrated in vac-
uum. The residue was purified by column chromatography to give
567 mg (90.7% yield) of the target N-[bis(4-trifluoromethyl-
phenyl)phosphino]-(S)-1-[2-(diphenylphosphino)phenyl]ethyla-
(S)-1b
(S)-2e
(S)-2f
(S)-2g
>99
>99
>99
80
10
(S)-2h >99
a
Hydrogenations were performed in 2 mL of the indicated solvent with 0.5 mmol
of substrate and 1 mol % of catalyst, prepared in situ from [Rh(COD)2]BF4 and
1.1 equiv of ligand, at room temperature and a H2 pressure of 10 atm for 24 h.
b
Conversions and enantiomeric excesses were determined by GC on a chiral c-
DEX-225 column for 12 and a chiral CP-Chiralsil-L-Val column for 14. The absolute
configuration was determined by comparing the GC retention times with GC data in
the literature.6c
mine 2a as a viscous oil. ½a D25
ꢀ
¼ þ3:2 (c 0.72, ClCH2CH2Cl); 1H NMR
(400 MHz, CDCl3): d 1.35 (d, J = 6.8 Hz, 3H), 5.15 (m, 1H), 6.86–7.57
(m, 22H); 31P NMR (162 MHz, CDCl3): d ꢁ16.7, 34.2; 13C NMR
(100 MHz, CDCl3): d 25.1, 53.4, 124.1 (q, J = 271 Hz), 125.4, 127.3,
128.5, 128.6, 128.7, 128.8, 129.5, 133.8, 133.9, 134.0, 134.2,
136.7, 143.2, 150.4, 150.7; HR-MS (EI): m/z = 625.1526, calcd for
C34H27F6NP2 (M+): 625.1523.
3. Conclusion
In conclusion, the substrate scope presented herein highlights
the versatility of this readily available, air-stable phosphine–ami-
nophosphine ligand class in the Rh-catalyzed asymmetric hydroge-
nation of various functionalized olefins. The modularity in the
synthesis of these ligands allows the optimization of the ligand
structure to be easily carried out. Ligand screening disclosed that
ligand structure has significant impact on the catalytic activity
and enantioselectivity. Ligand 2d, bearing an N–H proton and
two F-atoms on the 3,5-positions of the phenyl ring of the amin-
ophosphino moiety, exhibited the best catalytic performance in
the Rh-catalyzed asymmetric hydrogenation of enamides and (Z)-
b-aryl-b-(acylamino)acrylates, whereas ligand 1b with an N-
methyl group and a diphenylphosphinoamino moiety showed
higher enantioselectivities in the hydrogenation of (Z)-b-alkyl-b-
(acylamino)acrylates and dimethyl itaconate. However, the
present catalytic system is inefficient for the hydrogenation of
4.2.1. N-[Bis(4-methylphenyl)phosphino]-(S)-1-[2-(diphenyl-
phosphino)phenyl]ethylamine 2b
½
a 2D5
ꢀ
¼ ꢁ5:2 (c 0.25, ClCH2CH2Cl); 1H NMR (400 MHz, CDCl3): d
1.36 (d, J = 7.6 Hz, 3H), 2.30 (s, 6H), 5.15 (m, 1H), 6.84–7.57 (m,
22H); 31P NMR (162 MHz, CDCl3):
d
-16.9, 33.5; 13C NMR
(100 MHz, CDCl3): d 21.5, 25.6, 53.2, 126.3, 126.9, 128.5, 128.7,
128.9, 129.4, 131.1, 131.2, 131.3, 131.4, 133.7, 133.8, 133.9,
134.0, 134.2, 138.0, 138.1, 151.6; HR-MS (EI): m/z = 517.2093,
calcd for C34H33NP2 (M+): 517.2088.
4.2.2. N-{Bis[3,5-bis(trifluoromethyl)phenyl]phosphino}-(S)-1-
[2-(diphenylphosphino)phenyl]ethylamine 2c
½ ꢀ
a 2D5
¼ þ24:7 (c 0.59, ClCH2CH2Cl); 1H NMR (400 MHz, CDCl3): d
(E)-b-alkyl-b-(acylamino)acrylates and a-dehydroamino acid ester.
1.41 (d, J = 6.6 Hz, 3H), 5.17 (m, 1H), 6.86–7.81 (m, 20H); 31P NMR
(162 MHz, CDCl3): d ꢁ16.7, 33.8; 13C NMR (100 MHz, CDCl3): d
24.6, 53.7, 122.8, 123.1 (q, J = 271 Hz), 125.7, 127.6, 128.5, 128.6,
128.9, 129.5, 130.7, 130.9, 131.1, 131.8, 131.9, 133.7, 133.9,
134.1, 144.0, 144.2, 149.7; HR-MS (EI): m/z = 761.1280, calcd for
C36H25F12NP2 (M+): 761.1271.
4. Experimental
4.1. General
All reactions were carried out under a nitrogen or argon atmo-
sphere unless otherwise noted. Anhydrous procedures were con-
ducted using oven-dried or flame-dried glassware and standard
syringe and cannula transfer techniques. Hydrogenation was per-
formed in a stainless steel autoclave. Solvents were of reagent
grade, dried, and distilled before use following standard proce-
dures. Compounds (S)-4a and (S)-4b were prepared according to
our recently reported method.9 Chlorodi(aryl)phosphines were
prepared according to the literature method.11 Hydrogenation
4.2.3. N-[Bis(3,5-difluorophenyl)phosphino]-(S)-1-[2-(diphenyl-
phosphino)phenyl]ethylamine 2d
½
a 2D5
ꢀ
¼ þ10:2 (c 1.35, ClCH2CH2Cl); 1H NMR (400 MHz, CDCl3): d
1.25 (d, J = 8.0 Hz, 3H), 5.11 (m, 1H), 6.74–7.45 (m, 20H); 31P NMR
(162 MHz, CDCl3): d -16.7, 34.8; 13C NMR (100 MHz, CDCl3): d 25.1,
53.2, 104.2 (t, J = 26 Hz), 113.4 (t, J = 25 Hz), 125.8, 125.9, 127.3,
128.5, 128.6, 128.8, 129.5, 133.8, 133.9, 134.0, 134.5, 136.4,

424
X.-M. Zhou et al. / Tetrahedron: Asymmetry 21 (2010) 420–424
145.7, 150.0, 162.9 (d, J = 251 Hz); HR-MS (EI): m/z = 561.1402,
Acknowledgments
calcd for C32H25F4NP2 {M+}: 561.1398.
Financial support from the National Natural Science Foundation
of China (20802076), Program for Liaoning Innovative Research
Team in University (2008T107), and the Knowledge Innovation
Program of the Chinese Academy of Sciences (DICP-S200802) is
gratefully acknowledged.
4.2.4. N-Methyl-N-[bis(4-trifluoromethylphenyl)phosphino]-
(S)-1-[2-(diphenylphosphino)phenyl]ethylamine 2e
½
a 2D5
ꢀ
¼ þ56:0 (c 1.16, ClCH2CH2Cl); 1H NMR (400 MHz, CDCl3): d
1.49 (d, J = 6.8 Hz, 3H), 2.15 (s, 3H), 5.26 (m, 1H), 6.92–7.69 (m,
22H); 31P NMR (162 MHz, CDCl3):
d
-16.6, 50.6; 13C NMR
References
(100 MHz, CDCl3): d 22.1, 35.2, 45.9, 59.8, 125.1, 126.5, 126.9
(J = 271 Hz), 127.4, 128.4, 128.5, 128.6, 128.7, 129.1, 133.7, 133.9,
134.1, 134.7, 134.9, 135.5, 135.7, 140.8, 148.9; HR-MS (EI):
m/z = 639.1672, calcd for C35H29F6NP2 {M+}: 639.1679.
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a 2D5
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1.49 (d, J = 8.0 Hz, 3H), 2.15 (s, 3H), 2.30 (s, 6H), 5.20 (m, 1H), 6.91–
7.60 (m, 22H); 31P NMR (162 MHz, CDCl3): d -17.2, 48.6; 13C NMR
(100 MHz, CDCl3): d 22.3, 22.7, 59.9, 126.8, 126.9, 128.4, 128.5,
128.6, 128.8, 129.1, 131.8, 132.0, 132.7, 132.9, 133.8, 134.0,
137.6, 150.2, 150.5; HR-MS (EI): m/z = 531.2256, calcd for
C35H35NP2 {M+}: 531.2245.
4.2.6. N-Methyl-N-{bis[3,5-bis(trifluoromethyl)phenyl]phos-
phino}-(S)-1-[2-(diphenylphosphino)phenyl]ethylamine 2g
½
a 2D5
ꢀ
¼ þ58:7 (c 0.16, ClCH2CH2Cl); 1H NMR (400 MHz, CDCl3): d
1.48 (d, J = 8.8 Hz, 3H), 2.31 (s, 3H), 5.27 (m, 1H), 6.92–7.86 (m,
20H); 31P NMR (162 MHz, CDCl3):
d
ꢁ15.8, 52.0; 13C NMR
(100 MHz, CDCl3): d 22.5, 34.7, 59.8, 122.8, 123.2 (q, J = 271 Hz),
126.2, 127.8, 128.5, 128.6, 128.7, 128.8, 128.9, 129.1, 131.2,
132.1, 132.3, 133.6, 133.8, 133.9, 134.2, 135.8, 136.3, 136.6,
141.8, 147.6; HR-MS (EI): m/z = 775.1421, calcd for C37H27F12NP2
{M+}: 775.1427.
4.2.7. N-Methyl-N-[bis(3,5-difluorophenyl)phosphino]-(S)-1-
[2-(diphenylphosphino)phenyl]ethylamine 2h
½
a 2D5
ꢀ
¼ þ54:8 (c 0.45, ClCH2CH2Cl); 1H NMR (400 MHz, CDCl3): d
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20H); 31P NMR (162 MHz, CDCl3):
d
ꢁ16.6, 52.8; 13C NMR
(100 MHz, CDCl3): d 21.7, 35.5, 59.8, 104.0 (t, J = 26 Hz), 114.0 (t,
J = 23 Hz), 114.8 (t, J = 23 Hz), 126.5, 127.5, 128.5, 128.6, 128.7,
128.8, 129.1, 133.7, 133.9, 134.0, 134.1, 136.7, 162.9 (d,
J = 251 Hz); HR-MS (EI): m/z = 575.1567, calcd for C33H27F4NP2
{M+}: 575.1555.
4.3. General procedure for hydrogenation
To a solution of [Rh(COD)2]BF4 (2.0 mg, 0.005 mmol) in anhy-
drous and degassed solvent (1 mL), which was placed in a nitro-
gen-filled glovebox, was added phosphine–aminophosphine
ligand 2 (0.0055 mmol). The reaction mixture was stirred at room
temperature for 30 min and then a solution of olefin (0.5 mmol) in
1 mL of solvent was added. The mixture was transferred to a Parr
stainless autoclave. The autoclave was purged three times with
hydrogen, and a hydrogen pressure of 10 atm was maintained.
The hydrogenation was performed at room temperature for 24 h.
After carefully releasing the hydrogen, the solvent was removed.
The residue was filtered through a short SiO2 column to remove
the catalyst. The filtrate was concentrated under reduced pressure
and the enantiomeric excess was determined by GC on a chiral
column.
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