Rhodium-catalyzed asymmetric hydrogenation with aminophosphine ligands derived from 1,1′-binaphthyl-2,2′-diamine

Article abstract of DOI:10.1016/S0040-4039(02)01510-1

Chiral ligands 2,2′-bis(dicyclohexylphosphinoamino)-1,1′-binaphthyl and 2,2′-bis[bis(3,5-dimethylphenyl)phosphinoamino]-1,1′-binaphthyl were synthesized by reacting 1,1′-binaphthyl-2,2′-diamine with dicyclohexylchlorophosphine and bis(3,5-dimethylphenyl)chlorophosphine, respectively. Application of these ligands to the Rh-catalyzed asymmetric hydrogenation of a variety of amidoacrylic acids and esters provided chiral amino acid derivatives with excellent enantioselectivities (up to 99% e.e. and quantitative yields).

Full text of DOI:10.1016/S0040-4039(02)01510-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 6803–6806
Rhodium-catalyzed asymmetric hydrogenation with
aminophosphine ligands derived from 1,1%-binaphthyl-2,2%-diamine
Rongwei Guo, Xingshu Li, Jing Wu, Wai Him Kwok, Jian Chen, Michael C. K. Choi* and
Albert S. C. Chan*
Open 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
Received 7 May 2002; revised 10 July 2002; accepted 19 July 2002
Abstract—Chiral ligands 2,2%-bis(dicyclohexylphosphinoamino)-1,1%-binaphthyl and 2,2%-bis[bis(3,5-dimethylphenyl)phosphino-
amino]-1,1%-binaphthyl were synthesized by reacting 1,1%-binaphthyl-2,2%-diamine with dicyclohexylchlorophosphine and bis(3,5-
dimethylphenyl)chlorophosphine, respectively. Application of these ligands to the Rh-catalyzed asymmetric hydrogenation of a
variety of amidoacrylic acids and esters provided chiral amino acid derivatives with excellent enantioselectivities (up to 99% e.e.
and quantitative yields). © 2002 Elsevier Science Ltd. All rights reserved.
Asymmetric hydrogenation reactions are important in
practical organic synthesis ranging from laboratory
scale research to large scale production.1 Chiral phos-
phine ligands play a significant role in various metal-
catalyzed asymmetric reactions.2–7 Over the past three
decades, most effort on asymmetric hydrogenation has
been focused on the use of rhodium and ruthenium
catalysts containing chiral phosphine ligands. Recently,
it has been shown that some of the results obtained
with phosphinite,8 phosphite,9 phosphonite,10 or
phosphoroamidite11 ligands can match those obtained
by using phosphines. Rhodium catalysts bearing
aminophosphine ligands also have shown good to
excellent enantioselectivity and high reactivity in asym-
metric hydrogenation.12,13 Since many effective phos-
phine ligands are quite difficult to prepare, the search
for easily prepared and highly effective new chiral
ligands is still of high interest.
Schmid,14 Pregosin15 and RanjanBabu8b,16 reported that
in asymmetric hydrogenation, the enantioselectivities of
transition metal phosphine/phosphinite catalysts were
significantly influenced by the substituents on the phos-
phorous atoms. In our initial study, we found the
rhodium catalyst containing bidentate aminophosphine
1 (BDPAB)17a,b to be effective in the hydrogenation of
enamides13 and dehydroamino acid derivatives.17c
Expanding the scope of this study, we developed a
series of substituted bisaminophosphine ligands and
tested their effectiveness in the rhodium-catalyzed
hydrogenation of amidoacrylic acids and esters. The
ligands 2,2%-bis(diphenylphosphinoamino)-1,1%-binaph-
thyl
1
(BDPAB), 2,2%-bis[bis(3,5-dimethylphenyl)-
phosphinoamino]-1,1%-binaphthyl
3
(Xyl-BDPAB)18
and 2,2%-bis(dicyclohexylphosphinoamino)-1,1%-binaph-
thyl 2 (Cy-BDPAB)19 were derived from 1,1%-binaph-
thyl-2,2%-diamine (BINAM) as shown in Scheme 1.
1. R = Phenyl
NHPR2
R2PCl/Et3N/DMAP
CH2Cl2, 00C-RT, 3 h
NH2
NH2
2. R = Cyclohexyl
NHPR2
3. R = 3,5-Dimethylphenyl
Scheme 1. Synthesis of bisaminophosphines.
Keywords: aminophosphine ligand; asymmetric hydrogenation; rhodium; amino acid derivatives.
* Corresponding authors. Tel.: 852-27665607; fax: 852-23649932; e-mail: bcachan@polyu.edu.hk
† A University Grants Committee Areas of Excellence Scheme in Hong Kong.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01510-1

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R. Guo et al. / Tetrahedron Letters 43 (2002) 6803–6806
ratio of substrate to catalyst was increased from 500 to
5000 (Table 2, entries 5, 6 and 7).
The experimental results revealed that rhodium cata-
lysts bearing these bisaminophosphine ligands gave
very different enantioselectivities in the hydrogenation
of methyl acetamidocinnamate (Table 1). When the
phenyl groups on the phosphorus of the aminophos-
phine ligand were replaced with cyclohexyl groups (i.e.
ligand 2), the reactivity of the rhodium catalyst
remained high, however, the enantioselectivity dropped
sharply. In contrast, the enantioselectivity was
enhanced greatly when the phenyl groups on the phos-
phorous were replaced with sterically hindered 3,5-
dimethylphenyl groups (i.e. ligand 3). The choice of
Expanding on the successful lead in the asymmetric
hydrogenation of acetamidocinnamate, we examined
the hydrogenation of other amidoacrylic acids and
esters20 and the results are summarized in Table 3. The
high enantioselectivities of the {Rh[(S)-3]}BF4 catalyst
in the hydrogenation of these substrates were relatively
independent of the substituents on the phenyl ring of
the substrate. This high efficiency offered an opportu-
nity for the preparation of a variety of chiral amino
acids with high enantiomeric purity. Under identical
conditions, the differences in enantioselectivites
between the {Rh[(S)-1]}+ and {Rh[(S)-3]}+ were quite
significant.
−
−
anions, such as BF4 or SbF6 , had little influence on
the enantioselectivity.
Further study revealed that the {Rh[(S)-3]}BF4 catalyst
remained highly active and enantioselective in the
hydrogenation of methyl acetamidocinnamate under
different conditions. The choice of solvent had little
influence on the enantioselectivity of the reaction
(Table 2, entries 1–5) and lowering the reaction temper-
ature gave only slightly higher ee (Table 2, entries 5, 8
and 9). The ee remained unchanged when the molar
In conclusion, a highly effective bisaminophosphine
ligand has been synthesized and used in the rhodium-
catalyzed asymmetric hydrogenation of amidoacrylic
acids and esters. Excellent enantiomeric excesses (96–
99%) have been achieved with the {Rh[(S)-3]}BF4 cata-
lyst for a variety of substrates. The application of the
Table 1. The asymmetric hydrogenation of methyl acetamidocinnamate catalyzed by rhodium complexes containing ligands
1, 2, and 3a
CO2Me
CO2Me
catalyst. S/C = 500
RT, MeOH, 50 psig. H2
Ph
NHCOMe
Ph
NHCOMe
Ligand
[Rh(COD)2]X
Eeb (%)
(S)-1
(S)-1
(S)-2
(S)-2
(S)-3
(S)-3
[Rh(COD)2]BF4
[Rh(COD)2]SbF6
[Rh(COD)2]BF4
[Rh(COD)2]SbF6
[Rh(COD)2]BF4
[Rh(COD)2]SbF6
90
91
11
13
98.5
98.6
a All reactions were completed within 10 min. The substrate concentrations were 0.25 M. The rhodium catalysts were prepared by reacting ligands
1–3 with [Rh(COD)2]X in dichloromethane at room temperature.
b S Configuration was obtained in all experiments.
Table 2. Effects of solvent, temperature and substrate-to-catalyst ratio on the asymmetric hydrogenation of methyl acetami-
a
docinnamate with {Rh[(S)-3]}BF4
CO2Me
CO2Me
{Rh[(S)-3]}BF4
50 psig H2
Ph
Ph
NHCOMe
NHCOMe
Entry
Solvent
Sub./cat.
Temp. (°C)
Ee (%)
1
2
3
4
5
6
7b
8
9
THF
500
500
500
500
500
2000
5000
500
rt
rt
rt
rt
rt
rt
rt
98
97
97
98
98
98
98
99
99
Acetone
CH2Cl2
EtOH
MeOH
MeOH
MeOH
MeOH
MeOH
0
500
−25
a Reactions were carried out under an initial hydrogen pressure of 50 psig. Quantitative conversions were obtained within 10 min.
b The initial hydrogen pressure was 50 psig and quantitative conversion was obtained within 30 min.

R. Guo et al. / Tetrahedron Letters 43 (2002) 6803–6806
6805
a
Table 3. Asymmetric hydrogenation of amidoacrylic acids and esters with {Rh[(S)-3]}BF4
CO2R'
CO2R'
{Rh[(S)-3]}BF4, RT
MeOH, S/C = 500, 50 psig H2, 10 min
R
NHCOR"
NHCOR"
R
Entry
R
R%
R%%
Eeb (%)c
1
2
3
4
5
6
7
8
Ph
4-Me-Ph
4-MeO-Ph
4-O2N-Ph
4-AcO-Ph
2-Furanyl
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
H
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Ph
98(91)
98(89)
98(87)
96(82)
98(87)
98(84)
98(81)
97
97
98
98
98
3,4-Methylenedioxyl-Ph
2-Cl-Ph
3-Cl-Ph
4-F-Ph
4-Cl-Ph
4-Br-Ph
4-Cl-Ph
4-F-Ph
Ph
9
10
11
12
13
14
15
16
17
99
99
98
97
Ph
Me
Me
Me
H
H
Me
H
98
a The reactions were carried out at room temperature under 50 psig H2. Quantitative conversions were obtained within 10 min. The conversion
and enantiomeric excess were determined by GC analysis. Concentration of the substrates=0.25 M. The rhodium catalyst was prepared by
reacting (S)-3 with [Rh(COD)2]BF4 in CH2Cl2 at room temperature.
b All products had the S configuration.
c The data in parentheses were results obtained using {Rh[(S)-1]}BF4 as the catalyst.
catalyst to the asymmetric hydrogenation of other
classes of substrates is under investigation.
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Acknowledgements
We thank the Hong Kong Research Grants Council
(Project no. ERB03), the University Grants Committee
Areas of Excellence Scheme (Project No. AoE P/10-01),
and The Hong Kong Polytechnic University (ASD) for
financial support of this work.
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18. (S)-2,2%-Bis[bis(3,5-dimethylphenyl)phosphinoamino]-1,1%-
binaphthyl[(S)-Xyl-BDPAB], (S)-3. To a 50 ml round-
bottom Schlenk flask containing (S)-1,1%-binaphthyl-
2,2%-diamine (200 mg, 0.7 mmol) and DMAP (10 mg)
were added 10 ml dried CH2Cl2 and 0.7 ml dried Et3N.
The solution was cooled with an ice-bath to 0°C. Bis(3,5-
dimethylphenyl)phosphine chloride (450 mg, 1.6 mmol)
was added in a dropwise manner within 15 min. The
reaction mixture was stirred at room temperature for 3 h,
and the solvent was evaporated in vacuo. The residue was
purified using a flash silica gel column (toluene as the
eluent) under N2. Concentration of the filtrate and
removal of solvent under vacuum overnight gave (S)-3
(465 mg, 87% yield). Colorless crystals were obtained by
recrystallization from methanol/CH2Cl2 (v/v=4). 31P
NMR (CHCl3): l 26.1 (s). H NMR (CHCl3): l 2.35 (s,
1
12H), 2.8 (s, 12H), 5.00 (d, J=8.5 Hz, 2H), 6.96 (s, 2H),
6.98 (s, 2H), 7.00 (s, 2H), 7.01 (s, 2H), 7.04 (s, 2H), 7.10
(s, 2H), 7.42 (d, J=8.5 Hz, 2H), 7.50 (d, J=8.5 Hz, 2H),
7.56 (d, J=8.0 Hz, 2H), 8.10 (d, J=8.0 Hz, 2H), 8.18 (d,
J=9.0 Hz, 2H), 8.24–8.27 (dd, J=4.5, 9.0 Hz, 2H). 13C
NMR (CHCl3): methyl carbons 21.09, 21.11.
19. (S)-2,2%-Bis(dicyclohexylphosphinoamino)-1,1%-binaphthyl
[(S)-Cy-BDPAB], (S)-2. (S)-2 was synthesized in 78%
yield using a method similar to the preparation of (S)-3.
Colorless crystals were obtained by recrystallization from
ether. 31P NMR (CH2Cl2): l 42.77; 1H NMR (CH2Cl2): l
0.21–0.27 (m, 2H), 0.56–0.61 (m, 2H), 0.73–1.60 (m,
40H), 3.77 (d, J=10.5 Hz, 2H), 6.84 (d, J=7.5 Hz, 2H),
7.03–7.10 (m, 4H), 7.67 (d, J=7.5 Hz, 2H), 7.73 (d,
J=9.5 Hz, 2H), 7.78–7.81 (dd, J=4.5, 9.0 Hz, 2H).
20. A typical procedure for the rhodium-catalyzed asymmetric
hydrogenation of amidoacrylic acids and esters. In a glove-
box 0.01 mmol [Rh(COD)2]BF4, 0.01 mmol of the
bisaminophosphine ligand and 1 ml dried CH2Cl2 were
placed in a 4 ml glass bottle and the mixture was stirred
at room temperature for 1 h to prepare a stock solution
of the catalyst. In a typical experiment, 10 ml (0.0001
mmol) of the catalyst solution was added in a 50 ml
autoclave which was charged with 0.05 mmol substrate
and 190 ml solvent. The autoclave was closed and the
atmosphere was displaced by hydrogen several times and
finally 50 psig H2 was charged. The mixture was stirred at
rt for 10 min before releasing the H2. The enantiomeric
excess and conversion were determined by GC. The
hydrogenation product of acetamidoacrylic acid was con-
verted to its methyl ester before the GC analysis with a
capillary chiral column (CHROMPACK, CP Chirasil-
DEX CB, 25 m×0.25 mm). Other hydrogenation products
were analyzed using a (CHROMPACK, Chirasil-L-Val,
25 m×0.25 m) column.