Highly enantioselective hydrogenation of enamides catalyzed by rhodium-monodentate phosphoramidite complex derived from H8-BINOL

Article abstract of DOI:10.1016/j.tetasy.2003.07.005

A series of monodentate phosphoramidite ligands derived from H ₈-BINOL have been synthesized. The ligands are used in the Rh-catalyzed asymmetric hydrogenation of enamides to give the acetamides in up to 99% ee.

Full text of DOI:10.1016/j.tetasy.2003.07.005

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 14 (2003) 2687–2691
Highly enantioselective hydrogenation of enamides catalyzed by
rhodium-monodentate phosphoramidite complex derived from
H -BINOL
8
a,b
a
a
a
a
a
Xingshu Li, Xian Jia, Gui Lu, Terry T.-L. Au-Yeung, Kim-Hung Lam, Thomas W. H. Lo
a,
and Albert S. C. Chan *
a
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, China
b
Department of Chemistry, The South-West Nationality College, Chengdu, China
Received 10 May 2003; accepted 22 July 2003
Abstract—A series of monodentate phosphoramidite ligands derived from H -BINOL have been synthesized. The ligands are used
8
in the Rh-catalyzed asymmetric hydrogenation of enamides to give the acetamides in up to 99% ee.
©
2003 Elsevier Ltd. All rights reserved.
1
1
1
. Introduction
dled interest in monodentate ligands and the effective-
ness of the octahydrobinaphthyl backbone in
10
The asymmetric catalytic hydrogenation of enamides
provides a general and convenient access to chiral
amides or amine derivatives. Kagan et al. first recog-
nized the feasibility of this reaction in 1975 and
achieved up to 90% ee for some substrates by employ-
ing a Rh(I)–DIOP system. In 1996, Burk et al.
reported an important advance in the enantioselective
hydrogenation of arylenamides with Rh catalysts con-
asymmetric hydrogenations, we initiated a study of
the synthesis of a number of monodentate phospho-
ramidites derived from H -BINOL (Fig. 1) and their
applications in the Rh-catalyzed asymmetric hydro-
genation of enamides. Herein we report the results of
this study in comparison with those obtained using the
8
1
11b,j–l
original Monophos ligands.
2
taining Duphos and BPE ligands. Later, a number of
structurally diverse but effective ligands, such as H -
8
3
4
5
BDPAB, Binaphane and the likes, Pennphos, 1,4-
2. Results and discussions
6
7
diphosphines,
modified Duphos,
P-stereogenic
8
9
ligands, and ortho-substituted BIPHEP, for this reac-
In our preliminary study, N-(1-phenylethenyl) acet-
amide 3 was used as a model substrate for testing the
tion were also reported.
Our interest in catalytic asymmetric synthesis is focused
on the development of effective chiral ligands, which
can be easily prepared so that the related chemistry can
be widely used. That BINOL can be expediently synthe-
sized on a large scale and that H -BINOL can be
8
readily obtained from BINOL via hydrogenation ren-
dered H -BINOL an interesting starting material for
8
10
the preparations of chiral ligands. Spurred by a rekin-
*
0
Corresponding author. Tel.: 852-27665607; fax: 852-23649932;
e-mail: bcachan@polyu.edu.hk
Figure 1.
957-4166/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2003.07.005

2
688
X. Li et al. / Tetrahedron: Asymmetry 14 (2003) 2687–2691
catalytic performance of the catalysts containing chiral
ligands. Common factors governing the enantioselectiv-
ities of the reaction were examined. The results shown
in Table 1 indicated that the enantioselectivity of the
catalysts at 0°C was sensitive to the choice of solvent
when 2a was chosen as the chiral ligand (THF: 91.2%
ee, dichloromethane: 90.4% ee, acetone: 84.5% ee,
methanol: 40.0% ee). On the other hand, hydrogen
pressure had relatively little effect on the enantioselec-
tivity (entries 4, 9–10). The reaction temperature was
also an important factor. Significant increase in enan-
tioselectivity was observed at lower reaction tempera-
tures and the ee reached a plateau at −10°C. Further
decrease of temperature did not bring about further
enhancement in enantioselectivity. Under the optimal
conditions, 96.2% ee was obtained (entry 11). These
results compared favorably with the results of Rh-1
catalyzed asymmetric hydrogenation of enamides,
the substrates. The highest ee (99%) was realised for 6
which contained a p-CF group on the aromatic ring
3
(entry 4).
In conclusion, H -Monophos 2a was found to be an
8
effective ligand for the Rh-catalyzed asymmetric hydro-
genation of enamides.
3. Experimental
All experiments were carried out under a nitrogen
atmosphere using standard Schlenk techniques or in a
glovebox. Flash column chromatography was per-
formed on basic alumina (Merck Kieselgel 60, particle
size 0.032–0.063 mm). Tetrahydrofuran (THF) was dis-
tilled from sodium benzophenone ketyl prior to use.
Methanol was distilled from magnesium/iodine.
1
1g
which gave 50–96% ee. Other listed ligands were also
investigated. The results demonstrate that there are no
substantial differences between ligands 2b and 2c
Dichloromethane and acetone was distilled from CaH
2
1
31
13
and P O , respectively. H, P and C NMR were
2
5
recorded on a Varian AS 500 at room temperature
using CDCl3 as solvent. Enantiomeric excesses were
determined by gas chromatographic analyses conducted
on a HP 4890A or HP 5890 series II system.
(
2
entries 5 and 6) with 2a. However, when ligand 2d or
e was used in the reaction, the enantioselectivity
decreased dramatically to 50.1% and 62.5% ee (entries 7
and 8), respectively. Considering the relatively simple
preparation of ligand 2a, we selected 2a for further
study of this reaction.
3.1. General procedure for the synthesis of 2b–e
Phosphorus trichloride (0.3 mL, 3.4 mmol) and triethyl-
amine (1.2 mL, 8.6 mmol) were transferred via a
syringe into a 100 mL round-bottomed flask containing
Various enamides were used in the study of the enan-
tioselectivity of H -Monophos 2a under the optimal
8
conditions (Table 2). Ee values were found to be consis-
tently 3% higher in most cases in comparison with
those obtained with Rh-1 as catalyst, in accord with a
H -BINOL (0.88 g, 3.0 mmol) in toluene (30 mL) at
8
0°C under a nitrogen atmosphere. After the mixture
was kept stirring for 6 h, the volatiles were removed
under vacuum. A solution of the amine (3.9 mmol) and
triethylamine (0.6 mL, 4.3 mmol) in toluene (30 mL)
was added to the above flask and the mixture was
allowed to react overnight. The resulting mixture was
purified through a Al O -packed column with toluene
1
1f
recent finding. This is probably attributable to the
larger torsional dihedral angle in 2a. However the ee’s
decreased abruptly for substrates 10, 11 (entries 8–10)
and 12 (Scheme 1) due possibly to the larger steric bulk
of both the octahydrobinaphthyl backbone of 2a and
2
3
Table 1. Asymmetric hydrogenation of enamide 3 catalyzed by Rh-monodentate phosphoramidite ligands derived from
S)-H -BINOL
(
8
Entry
Ligands
Solvent
CH Cl
H2 (psi)
T (°C)
Time (h)
Ee (%)a
1
2
3
4
5
6
7
8
9
2a
2a
2a
2a
2b
2c
2d
2e
2a
2a
2a
2a
300
300
300
300
300
300
300
300
150
500
300
300
0
0
0
0
0
0
0
0
0
3
3
3
3
3
3
3
3
3
3
6
8
90.4
40.0
84.5
91.2
91.0
91.1
50.1
62.5
87.1
89.1
96.2
96.1
2
2
MeOH
Acetone
THF
THF
THF
THF
THF
THF
THF
THF
10
11
12
0
−10
−20
THF
a
The ee’s were determined by chiral GC analysis using a Chrompack chiral fused silica gel 50 m×0.25 mm chirasil-
were found with a R configuration based on the comparison of the experimental results with published data.
L
-VAL column; all products
1
1k

X. Li et al. / Tetrahedron: Asymmetry 14 (2003) 2687–2691
2689
a
Table 2. Asymmetric hydrogenation of enamides catalysed by Rh-(S)-H -Monophos
8
Entry
Substrate
S/C (mol/mol)
T (°C)
Time (h)
Conversion (%)
Ee (%)b
1
2
3
4
5
6
7
8
9
3
4
5
6
7
8
9
10
10
11
100
100
100
100
100
100
100
50
−10
−10
−10
−10
−10
−10
−10
0
8
8
8
6
8
8
8
24
18
18
>99
>99
>99
>99
>99
>99
>99
>99
20
96
95
92
99
98
98
95
15
23
42
50
100
−10
−10
1
0
>99
a
Hydrogen pressure was 300 psi in all reactions.
The ee’s were determined by chiral GC analysis using a Chrompack chiral fused silica gel 50 m×0.25 mm chirasil-
were found with a R configuration based on the comparison of the experimental results with published data.
b
L
-VAL column; all products
1
1i
4
H), 2.50–2.60 (m, 2H), 2.18–2.22 (m, 2H), 1.60–1.71
13
(
m, 8H), 1.42–1.51 (d, J=7.5 Hz, 3H). C NMR (125
MHz, CDCl ): l 148.51, 146.07, 145.25, 137.94, 137.53,
3
1
1
2
34.13, 133.30, 129.37, 129.28, 128.85, 128.53, 127.07,
26.18, 119.12, 118.52, 51.15, 50.93, 29.19, 29.16, 27.79,
3
1
7.71, 25.44, 25.38, 22.77, 22.72, 22.59, 22.52. P NMR
145.8. Anal. calcd for
C H O NP (%): C, 75.83; H, 6.82; N, 3.16; P, 6.98.
(
200 MHz, CDCl3):
l
Scheme 1.
28
30
2
Found: C, 75.58; H, 6.86; N, 3.01; P, 6.81.
as an eluent. The eluates were concentrated in vacuum
to afford the phosphoramidite as solids.
3.1.3.
,5%,6,6%,7,7%,8,8%-octahydro-1,1%-bi-2-naphthyl phospho-
ramidite 2d. The general procedure was followed with
R)-N-methylphenethylamine as starting material.
(R)-N-Methyl-N-1-phenylethyl-(S)-
5
(
3
.1.1. N,N-Diethyl-(S)-5,5%,6,6%,7,7%,8,8%-octahydro-1,1%-
20
Yield: 76.9%. Analytical data: [h] =+92 (c 0.60,
bi-2-naphthyl phosphoramidite 2b. The general proce-
D
1
CH Cl ). H NMR (500 MHz, CDCl ): l 7.45–7.47 (m,
dure was followed with diethylamine as starting
material. Yield: 81.2%. Analytical data: [h] =+219 (c
2
2
3
2
0
2H), 7.37–7.41 (m, 2H), 7.27–7.30 (m, 1H), 7.03–7.08
(m 2H), 6.82–6.84 (d, J=7.5 Hz, 1H), 6.50–6.51 (d,
J=8.0 Hz, 1H), 4.74–4.78 (m, 1H), 2.59–2.83 (m, 6H),
D
1
2 2 3
0
7
2
6
.55, CH Cl ). H NMR (500 MHz, CDCl ): l 6.81–
.06 (m, 4H), 2.93–2.97 (m, 2H), 2.77–2.91 (m, 6H),
.61–2.75 (m, 2H), 2.22–2.33 (m, 2H), 1.73–1.80, m,
2
.21–2.30 (m, 2H), 1.97–1.98 (d, J=4.5 Hz, 3H), 1.72–
13
1.78 (m, 6H), 1.54–1.55 (d, J=7.5 Hz, 3H), 1.50–1.53
H), 1.52–1.59 (m, 2H), 1.00–1.03 (t, J=7 Hz, 6H).
C
13
(m, 2H). C NMR (125 MHz, CDCl ): l 148.81,
NMR (125 MHz, CDCl ): l 148.91, 148.36, 148.33,
3
3
1
1
1
48.55, 148.52, 142.09, 142.07, 138.02, 138.00, 137.30,
34.07, 132.81, 129.31–129.41 (m), 129.18, 128.10–
28.26 (m), 127.67–127.76 (m), 127.05–127.15 (m),
1
37.90, 137.88, 137.39, 133.87, 132.78, 128.10–129.36
(
m), 128.09, 118.41, 118.39, 118.36, 37.94–38.11 (m),
2
1
9.09–29.21(m), 27.69–27.80 (m), 22.56–22.84 (m),
31
118.76 (m), 118.36–118.42 (m), 55.21–55.66 (dd), 29.00–
29.33 (m), 27.73–27.84 (m), 26.61–26.63 (m), 22.60–
4.67–14.74 (m). P NMR (200 MHz, CDCl ): l 144.8.
3
+
HRMS calcd for mass: 396 (M +1, 100%). HRMS
calcd for C24 H NO P: 395.2014. Found: 395.2011.
31
2
2.83 (m), 18.00–18.04 (m). P NMR (200 MHz,
+
30
2
CDCl ): l 142.9. HRMS calcd for mass: 458 (M +1,
3
1
00%). HRMS calcd for C H NO P: 457.2171.
29 32 2
Found: 457.2168.
3.1.2. (R)-N-1-Phenylethyl-(S)-5,5%,6,6%,7,7%,8,8%-octahy-
dro-1,1%-bi-2-naphthyl phosphoramidite 2c. The general
procedure was followed with (R)-phenylethylamine as
3
.1.4. N-(1-Pyrrolidinyl)-(S)-5,5%,6,6%,7,7%,8,8%-octahydro-
,1%-bi-2-naphthyl phosphoramidite 2e. The general pro-
1
20
starting material. Yield: 71.6%. Analytical data: [h] =
D
cedure was followed with pyrrolidine as starting
1
+
85 (c 0.55, CHCl ). H NMR (500 MHz, CDCl ): l
20
3
3
material. Yield: 77.3%. Analytical data: [h] =+238 (c
D
6
.20–7.41 (m, 9H), 4.38–4.40 (m, 1H), 2.61–2.80 (m,
1
0
.43, CH Cl ). H NMR (500 MHz, CDCl ): l 7.02–
2
2
3

2
690
X. Li et al. / Tetrahedron: Asymmetry 14 (2003) 2687–2691
7
2
2
2
.10 (d, J=40.5 Hz, 2H), 6.95–6.97 (d, J=10.0 Hz,
N-[1-(1-Naphthalenyl)ethyl]acetamide
H), 6.81–6.83 (d, J=8.5 Hz, 1H), 3.04–3.59 (m, 2H),
.72–2.95 (m, 6H), 2.61–2.68 (m, 2H), 2.19–2.30 (m,
Oven temperature: 165°C, t
(S).
R
=41.8 min (R), 43.8 min
13
H), 1.43–1.91 (m, 12H). C NMR (125 MHz, CDCl3):
N-(1-Phenylpropyl)acetamide
Oven temperature: 150°C, t =31.2 min (R), 32.7 min
l 148.95, 148.47, 148.44, 137.73, 137.31, 133.67, 132.75,
1
1
2
29.11–129.27 (m), 128.85–128.91 (m), 128.32, 128.31,
18.37 (m), 45.17–45.29 (m), 28.94–29.18 (m), 27.52–
7.70 (m), 25.71–25.74 (m), 22.49–22.76 (m). P NMR
R
(
S).
3
1
(
200 MHz, CDCl ): l 144.4. HRMS calcd for
3
Acknowledgements
C H NO P: 393.1858. Found: 393.1851.
24
28
2
We thank the Hong Kong Research Grants Council
Central Allocation Fund (ERB03), the University
Grants Committee Areas of Excellence Scheme in Hong
Kong (AoE P/10-01) and the Hong Kong Polytechnic
University Area of Strategic Development Fund for
financial support of this study.
3
.2. Typical procedure for the hydrogenation of
enamides
A stock catalyst solution was prepared in situ by mix-
ing [Rh(COD) ]BF (2.0 mg, 0.005 mmol) and the
2
4
phosphoramidite 2a–e (0.01 mmol) in THF (1.0 mL).
The mixture was stirred for 10 min. An appropriate
amount of this catalyst solution (ca. 0.2 mL) was
transferred into a 50 mL stainless steel autoclave with a
glass liner containing a predetermined amount of the
enamide substrate (1.0 mmol) and a magnetic stirring
bar. Hydrogen gas was charged into the reactor at the
required temperature and pressure and the solution was
stirred for a specified period of time. After the reaction
was complete, the hydrogen gas was released and the ee
value of the product was measured directly from the
reaction mixture by GC without further purification.
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