Aminophosphine phosphinites derived from chiral 1,2-diphenyl-2-aminoethanols: Synthesis and application in rhodium-catalyzed asymmetric hydrogenation of dehydroamino acid derivatives

Article abstract of DOI:10.1016/S0040-4020(00)00481-6

A series of chiral aminophosphine phosphinites DPAMPPs was synthesized from optically active 1,2-diphenyl-2-aminoethanols. The erythro-DPAMPPs were found to serve as excellent ligands for rhodium-catalyzed asymmetric hydrogenation of dehydroamino acid derivatives. For an array of dehydroamino acid precursors, remarkably high enantioselectivity (up to 98.4% e.e.) and reactivity (the ratio of substrate/catalyst up to 10000) were observed. Some factors controlling the enantioselectivity were examined and discussed. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00481-6

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 5857±5863
Aminophosphine Phosphinites Derived from Chiral
1,2-Diphenyl-2-aminoethanols: Synthesis and Application in
Rhodium-Catalyzed Asymmetric Hydrogenation of
Dehydroamino Acid Derivatives
a
a
a
a
Rongliang Lou,a Aiqiao Mi,a, Yaozhong Jiang, Yong Qin, Zhi Li, Fangmin Fu and
*
Albert S. C. Chanb
aUnion Laboratory of Asymmetric Synthesis, Chengdu Institute of Organic Chemistry, Academia Sinica, Chengdu 610041,
People's Republic of China
bOpen Laboratory of Chirotechnology and Department of Applied Biology and Chemical Technology,
The Hong Kong Polytechnic University, Hong Kong, People's Republic of China
Received 5 January 2000; revised 15 May 2000; accepted 1 June 2000
AbstractÐA series of chiral aminophosphine phosphinites DPAMPPs was synthesized from optically active 1,2-diphenyl-2-aminoethanols.
The erythro-DPAMPPs were found to serve as excellent ligands for rhodium-catalyzed asymmetric hydrogenation of dehydroamino acid
derivatives. For an array of dehydroamino acid precursors, remarkably high enantioselectivity (up to 98.4% e.e.) and reactivity (the ratio of
substrate/catalyst up to 10000) were observed. Some factors controlling the enantioselectivity were examined and discussed. q 2000
Elsevier Science Ltd. All rights reserved.
Introduction
conveniently prepared by reaction of the corresponding
amino alcohol with chlorodiphenylphosphine in the
presence of an organic base. From the economic and tech-
nological standpoint, it is of substantial interest to develop
highly effective chiral aminophosphine phosphinite for
asymmetric hydrogenation. In this paper, we report the
results of systematical study on a series of novel chiral
aminophosphine phosphinite ligands derived from
(1R,2S)- or (1S,2R)-1,2-diphenyl-2-aminoethanol. The
cationic rhodium complexes of these ligands are found to
be highly effective catalysts for asymmetric hydrogenation
of dehydroamino acid derivatives.4
Due to their potential pharmacological application and their
incorporation in synthetic peptides, the development of
methods for the asymmetric synthesis of optically active
a-amino acids has been the subject of extensive research.1
Among various methods for the enantioselective synthesis
of these compounds, homogeneous asymmetric hydrogena-
tion catalyzed by rhodium complexes containing chiral
bidentate phosphine ligand is one of the most practical
process in asymmetric synthesis.2 During the last 10 years,
much effort has been devoted to developing chiral amino-
phosphine phosphinite ligands for asymmetric hydrogena-
tion.3 However, the development of aminophosphine
phosphinites is found to be less successful compared with
phosphine or phosphinite ligands. So far, no chiral amino-
phosphine phosphinite has been found to give the same high
enantioselectivity as the best chiral phosphine or phos-
phinite ligands. Despite this, aminophosphine phosphinites
still attract much attention because they possess the follow-
ing advantages: (1) Optically active amino alcohol used as
chiral source of aminophosphine phosphinite is available in
a variety of forms; (2) Aminophosphine phosphinite can be
Results and Discussion
Synthesis of chiral aminophosphine phosphinites
As shown in Scheme 1, three amino-phosphine phosphi-
nites, namely (1R,2S)-N,O-bis(diphenylphosphino)-1,2-di-
phenyl-2-(N-methyl) aminoethanol [abbreviated (1R,2S)-
DPAMPP], (1S,2R)-N,O-bis(diphenylphosphino)-1,2-diphenyl-
2-(N-methyl)aminoethanol [abbreviated (1S,2R)-DPAMPP] and
(1S,2S)-N,O-bis(diphenylphosphino)-1,2-diphenyl-2-(N-methyl)-
aminoethanol [abbreviated (1S,2S)-DPAMPP], were
synthesized from chiral 1,2-diphenyl-2-aminoethanols.
Thus, formylation of (1R,2S)-1 gave the corresponding
formamide (1R,2S)-2;5 borane reduction of (1R,2S)-2
Keywords: aminophosphine phosphinite; dehydroamino acid derivative;
asymmetric hydrogenation.
* Corresponding author. Fax: 186-28-5223978; e-mail: ulas@cioc.ac.cn
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00481-6

5858
R. Lou et al. / Tetrahedron 56 (2000) 5857±5863
Scheme 1. Synthetic routes to chiral aminophosphine phosphinites. Reaction conditions: (a) HCOOEt, TsOH, re¯ux, 3 h; (b) BH3±THF, r.t., 24 h; (c) ClPPh2,
NEt3, benzene, 24 h; (d) i. SOCl2; ii. 50% NaOH.
afforded N-methyl product (1R,2S)-3;6 then the desired
aminophosphine phosphinite (1R,2S)-DPAMPP was
prepared in a yield of 54% by reaction of compound
(1R,2S)-3 with chlorodiphenylphosphine in the presence
of triethylamine.3e Similarly, (1S,2R)-DPAMPP was synthe-
sized using the corresponding chiral amino alcohol (1S,2R)-
1 as starting material. For preparation of (1S,2S)-DPAMPP,
a threo-isomer of (1R,2S)- or (1S,2R)-DPAMPP, (1R,2S)-2
was treated with thionyl chloride followed by hydrolysis
with aqueous sodium hydroxide to give (1S,2S)-1,2-di-
phenyl-2-aminoethanol;7 (1S,2S)-1 was further transformed
to (1S,2S)-DPAMPP via the same steps as (1R,2S)-
DPAMPP. All these three DPAMPPs are white solids and
stable under argon atmosphere for at least one year as
Enantioselective hydrogenation of methyl (Z)-
acetamidocinnaminate 4 by Rh-DPAMPP catalysts
With these chiral DPAMPPs in hands, we ®rstly investi-
gated the homogeneous catalytic asymmetric hydrogenation
of methyl (Z)-2-acetamidocinnamate 4 (Scheme 2). The
catalyst was generally prepared in situ by mixing a solution
of a Rh precursor and a DPAMPP ligand. Some conclusions
can be drawn from these results shown in Table 1. (1)
Different Rh precursors lead to large variations in enantio-
selectivity and reactivity (comparing Entry 1 and Entry 2),
higher enantioselectivity was observed with cationic Rh
catalyst (Entry 2, 96.9% e.e.), only 27.0% e.e. and 31%
conversion was obtained with the neutral Rh system even
if the reaction time was prolonged to 17 h. (2) Both
enantiomers of phenylalanine derivatives can be prepared
in the same enantioselectivity by using the appropriate
enantiomer of DPAMPP (Entry 2, 3). (3) The con®guration
of ligand has a large effect on the enantioselectivity of
1
checked by H NMR and 31P NMR. Even in benzene, these
DPAMPPs are stable enough to be puri®ed by ¯ash column
chromatography over silica gel under an air atmosphere.
Undoubtedly, the stability of DPAMPPs is especially bene®cial
to their potential use in industrial processes.
Scheme 2.
Table 1. Rh-catalyzed asymmetric hydrogenation of methyl (Z)-2-acetamidocinnamate (the reaction was carried out in methanol under an initial hydrogen
pressure of 50 atm at room temperature with a ratio of substrate/catalyst of 100:1. The reaction time was 1 h unless otherwise noted)
Entry
Catalyst system
e.e. %a
Conv.%
Con®gurationb
1c
2
3
4
[Rh(COD)Cl]2/(1R,2S)-DPAMPP
27.0
96.9
98.3
40.6
31.1
100
100
100
S
S
R
R
[Rh(COD)Cl]2/AgBF4/(1R,2S)-DPAMPP
[Rh(COD)Cl]2/AgBF4/(1S,2R)-DPAMPP
[Rh(COD)Cl]2/AgBF4/(1S,2S)-DPAMPP
a The enantiomeric excesses were determined by GC on a Chrompack Chirasil-L-Val column.
b The absolute con®guration was assigned by comparison of optical rotation with reported value.
c The reaction time was 17 h.

R. Lou et al. / Tetrahedron 56 (2000) 5857±5863
5859
Figure 1.
reaction, hydrogenation using the erythro series (1R,2S)- or
(1S,2R)-DPAMPP as ligands gave high enantioselectivity
(Entry 2, 3) while a signi®cantly lower e.e. value was
observed with the thero ligand (1S,2S)-DPAMPP (Entry
4). It seems that the correct array of two phenyls in
DPAMPPs is important for high enantioselectivity. (4)
The sense of asymmetric induction is determined primarily
by the con®guration of the oxygen-bearing carbon, because
(1S,2R)- and (1S,2S)-DPAMPP gave the product with the
same con®guration (R)-phenylalanine (Entry 3, 4) whereas
(1R,2S)-DPAMPP gave (S)-enriched product (Entry 2), and
the lower enantioselectivity of (1S,2S)-DPAMPP implies
that the nitrogen-substituted chiral carbon affects greatly
the extent of the enantioselection.
active transition state complex formed from catalyst and
substrate.
For increasing enantioselectivity and reactivity of the reac-
tion, the optimal conditions were examined, such as the
effects of solvent (Table 2), hydrogen pressure (Table 3),
reaction temperature and substrate concentration (Table 4).
Asymmetric hydrogenation using (1R,2S)-DPAMPP as
ligand preceeded smoothly in methanol, acetone, THF and
isopropanol with a slight variation in e.e., and methanol
was the best solvent (Table 2). The optical yields were
independent of hydrogen pressure over the 1±80 atm
range, however the rate of hydrogenation decreases greatly
with lowering hydrogen pressure (Table 3). This suggests
that oxidative addition of hydrogen to the rhodium species
should be the rate-determining step, rather than the enantio-
determining step. An increase in reaction temperature
caused a slight decrease in enantioselectivity. Under an
initial hydrogen pressure of 10 atm with a ratio of
(1R,2S)-DPAMPP-Rh and methyl (Z)-acetamidocinnamate
(4) (S/C) of 100 in acetone, the e.e. value was decreased
from 96.3% to 95.7 and 95.0% as the reaction temperature
increases from 0 to 25 and 508C. This result is consistent
with that achieved with Ph-b-Glup9b but in contrast to those
with DIOP, DIPAMP and CHIRAPHOS.10 The enantio-
selectivity dropped slightly with decreasing the reactant
concentration (Table 4), and this is quite different
from the result with Rh-BINAP system,11 a possible
explanation is that at lower concentration, the hydrogena-
tion proceeds more slowly and is therefore more easily
subjected to the negative effect due to the erosion of
catalyst.
To our knowledge, the 98.3% e.e. obtained with (1R,2S) and
(1S,2R)-DPAMPP is the best result among those with other
aminophosphine phosphinites reported to date. Further-
more, the excellent enantioselectivity of erythro-DPAMPP
is also comparable to the best well-known chiral phosphine8
or phosphinite ligands.9 Pracejus had investigated asym-
metric hydrogenation of compound 4 using a series of
aminophosphine phosphinites 6, 7 and 8 as ligands (Fig.
1), only 75% e.e., 55% e.e. and 14% e.e. were obtained
respectively.3g Compared with our results (Entry 3, Table
1), it can be found that the enantioselectivity increases
dramatically with enhancement of the bulkiness of substi-
tutents on these aminophosphine-phosphinites. The high
enantioselectivity of erythro-DPAMPP is rationalized by
the two bulky phenyls on the C(1) and C(2) positions that
may increase the rigidity of the chiral ligand and are there-
fore bene®cial to stabilizing the spatial conformation of the
Table 2. The effect of solvent on hydrogenation of methyl (Z)-acetamido-
cinnamate 4 catalyzed by [((1R,2S)-DPAMPP)Rh(COD)]BF4 (reaction
conditions: 10 atm H2 pressure; 258C; S/Cˆ100; substrate concentration
(Csub)ˆ0.05 M; 100% conversion was observed after 1 h of reaction in all
cases)
Table 4. The effect of reactant concentration on the hydrogenation of meth-
yl (Z)-acetamidocinnamate
4 catalyzed by [((1R,2S)-DPAMPP)Rh-
(COD)]BF4 (reaction conditions: acetone as solvent; 10 atm of H2; 258C;
S/Cˆ100; 100% conversion)
Entry
Solvent
e.e.%
S:R
Entry
Substrate concentration (M)
e.e.%
S:R
1
2
3
4
MeOH
Acetone
THF
97.0
95.1
94.8
92.7
65.7:1
39.8:1
37.5:1
26.4:1
1
2
3
4
0.10
0.05
0.02
0.01
96.2
95.8
94.5
93.8
52.5:1
46.6:1
35.4:1
31.3:1
i-PrOH
Table 5. The effect of the ratio of substrate/catalyst on hydrogenation of
methyl (Z)-acetamidocinnamate 4 catalyzed by [((1S,2R)-DPAMPP)Rh-
(COD)]BF4 (the reaction was carried out under 50 atm of H2 at 258C in
methanol)
Table 3. The effect of hydrogen pressure on hydrogenation of methyl (Z)-
acetamidocinnamate 4 catalyzed by [((1R,2S)-DPAMPP)Rh(COD)]BF4
(reaction conditions: methanol as solvent; 258C; S/Cˆ100; Csubˆ0.05 M;
100% conversion)
Entry
Substrate/catalyst
Time (h)
e.e.%
Conv.%
Entry
H2 pressure (atm)
Time (h)
e.e.%
1
2
3
4
5
100
1000
10 000
50 000
100 000
1
4
16
64
64
98.3
97.5
97.0
97.0
93.0
100
100
100
82.7
41.7
1
2
3
4
80
50
20
1
0.5
1.0
1.0
4.0
96.8
96.9
96.4
97.2

5860
R. Lou et al. / Tetrahedron 56 (2000) 5857±5863
Scheme 3.
Table 6. Asymmetric hydrogenation of dehydroamino acid derivatives 9
catalyzed by [((1S,2R)-DPAMPP)Rh(COD)]BF4 (reaction conditions:
50 atm of H2; 258C; 1 h reaction time; S/Cˆ100; methanol used as solvent
unless otherwise noted; 100% conversion was observed in all cases. The
(R)-con®guration was obtained for all products)
Moreover, hydrogenation of methyl (Z)-acetamidocin-
namate was carried out at much higher ratio of substrate/
catalyst (S/C) using [((1S,2R)-DPAMPP)Rh(COD)]BF4 as a
catalyst, no signi®cant decrease of enantioselectivity was
observed even when the ratio of S/C was increased up to
50000 (Table 5, Entry 4). When the ratio of S/C was
10000, the reaction was complete within 16 h with 100%
conversion and 97.0% enantiomeric excess. This justi®es
the use of the Rh-DPAMPP catalyst on economic grounds.
Entry
Substrate
e.e.%a
R1
R2
R3
1
2
3
4
5
6
7
8
Ph
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Ph
Ph
Ph
Ph
Ph
Me
Ph
Ph
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
H
98.3
97.3
97.3
97.2
97.8
95.1
4-MeO±Ph
4-Me±Ph
4-F±Ph
4-Cl±Ph
3-Cl±Ph
2-Cl±Ph
4-Br±Ph
4-NO2±Ph
4-AcO±Ph
3-MeO±4-AcO±Ph
3,4-OCH2O±Ph
20-furanyl
Ph
4-Cl±Ph
4-Br±Ph
2-HO±Ph
2-Cl±3-AcO±4-MeO±Ph
Ph
Ph
Asymmetric hydrogenation of various dehydroamino
acid derivatives catalyzed by Rh-DPAMPP complex
92.3(98.4)b
98.0
97.5
After investigation of the optimal conditions, various
dehydroamino acid derivatives were used for (1S,2R)-
DPAMPP-Rh catalyzed hydrogenation (Scheme 3). The
results summarized in Table 6 indicate that the high enantio-
selectivity of (1S,2R)-DPAMPP was quite general for a
great deal of different dehydroamino acid precursors. In
all cases, the desired (R)-products were found to have e.e.
values of over 90.0%. As expected, (S)-products can be
prepared in a relatively high enantioselectivity by using
(1R,2S)-DPAMPP as ligand (see Tables 1±4).
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
95.6
98.1c
97.5
91.1
97.1
97.0
96.5
96.3
98.0c
96.5d
96.4d
97.4
H
H
H
H
4-NO2±Ph
H
H
PhCH2
Table 6 clearly showed that the structure of substrate
affected the outcome of hydrogenation. The enantiomeric
excesses are particularly high (more than 95.0% e.e., Entry
1±12 and Entry 14±21) when R1 is phenyl or its analogues
regardless of the substituents on their aromatic rings. For the
reaction performed in methanol, methyl (Z)-2-acetamido-3-
phenylacrylate 4 was reduced to give the highest e.e. (98.3%
e.e., Entry 1). A decrease of enantioselectivity was observed
when the R1 group of substrate 9 was replaced with hydro-
gen atom, alkyl and heteroaromatic ring (Entry 22, 23, 24
and 13). It was found that the presence of electron-with-
drawing groups on an ole®nic substrate enhances late-
transition metal binding constants and results in higher
enantioselectivity in asymmetric hydrogenation reaction.12
Me
Ph
Me
95.2d
94.8d
93.1
Et
a The e.e. values were determined by GC on a Chrompack Chirasil-L-Val
column unless otherwise noted.
b The data in parenthesis was obtained from hydrogenation in acetone.
c The e.e. values were determined by HPLC on a Chiralcel OD column.
d The e.e. values were determined by GC on a Chrompack Chirasil-L-Val
column after converting the products to the corresponding methyl
esters.
Scheme 4.

R. Lou et al. / Tetrahedron 56 (2000) 5857±5863
5861
However, the lower e.e.s obtained with methyl (Z)-2-aceta-
mido-3-furanylacrylate may be caused by the possible inter-
action between oxygen atom in furanyl and the Rh catalyst.
On the other hand, the para-substituents on 3-phenyl almost
showed no signi®cant effect on the enantioselectivity
regardless of their electron-withdrawing or electron-dona-
ting properties. Surprisingly, the difference of the substi-
tuted position for these groups results in an obviously
dissimilarity in e.e. (Entry 5, 6, 7). For example, only
92.3% e.e. was achieved for hydrogenation of methyl (Z)-
2-acetamido-3-(20-chlorophenyl)acrylate while hydrogena-
tion of its 30-chloro and 40-chloro analogues gave more than
95.0% enantioselectivity. More interestingly, using acetone
as solvent, hydrogenation of methyl (Z)-2-acetamido-3-(20-
chlorophenyl)acrylate gave a high e.e. of 98.4%, which was
also the best result reported to date. The R2 and R3 groups of
substrate 9 have a small effect on hydrogenation. Generally,
hydrogenation gave a slightly better e.e. when R2 was acetyl
and R3 was methyl.
ketyl; solvents used in hydrogenation were degassed by
three freeze±thaw cycles prior to use.
Materials
(1R,2S)- and (1S,2R)-1,2-Diphenyl-2-aminoethanols were
prepared on large scale in our laboratory.15 Chlorodiphenyl-
phosphine, AgBF4 and [Rh(COD)Cl]2 were purchased from
Aldrich Chemical Co. BH3±THF (1.5 M) was prepared
according to the literature method.16 All (Z)-2-acylamido-
3-arylacrylic acids were synthesized in accordance with the
process developed by Herbst.17 Their corresponding methyl
esters were prepared by the reaction of free acids with MeI
in the presence of KHCO3 in DMF. The preparation of ethyl
(Z)-2-acetamido-4-phenylcrotonate was achieved using the
literature procedure with slight modi®cation.18
(1R,2S)-1,2-Diphenyl-2-formamidoethanol, (1R,2S)-2. The
mixture of (1R,2S)-1,2-diphenyl-2-aminoethanol (2.0 g,
9.39 mmol) and p-toluene sulfonic acid (20 mg) were
heated to re¯ux in ethyl formate (40 mL) for 3 h. The excess
of ethyl formate was removed in vaccum. The residue was
recrystallized from ethanol to give 2.05 g (91% yield) of
desired product as a white solid: mp 204±2058C;
It is noticeable that these reactions have found wide
practical application in the synthesis of biologically active
molecules. For example, methyl (S)-2-acetamido-3-(3-
methoxy-4-acetoxyphenyl)-propionate 12, a crucial inter-
mediate for the synthesis of the well-known l-DOPA
13,13 could be synthesized in 97.4% e.e. by hydrogenation
of methyl (Z)-2-acetamido-3-(3-methoxy-4-acetoxy phenyl)-
acrylate 11 catalyzed by [((1R,2S)-DPAMPP)Rh(COD)]BF4
(Scheme 4). Similarly, enantioselective hydrogenation of
ethyl (Z)-2-acetamido-4-phenylcrotonate 14 gave the opti-
cally active homophenylalanine derivative 15 with 92.5%
e.e., which was also a key component of (S,S)-benazepril
16, an ACE (angiotensin converting enzyme) inhibitor
widely used as antihypertensive.14
[a]D20ˆ22.91 (0.64, EtOH); nmax(KBr): 3350, 1664 cm21
;
1H NMR (DMSO) d 4.77 (d, Jˆ6.8 Hz, 1H, OCH), 5.01 (dd,
J1ˆ6.9 Hz, J2ˆ9.3 Hz, 1H, NCH), 7.09±7.49 (m, 10H,
2£Ph), 7.89 (s, 1H, HCO), 8.57 (d, Jˆ9.3 Hz, 1H,
CONH). Anal. Calcd for C15H15NO2: C, 74.60; H, 6.27;
N, 5.81. Found: C, 74.32; H, 6.27; N, 5.68.
(1S,2R)-1,2-Diphenyl-2-formamidoethanol, (1S,2R)-2.
With the similar procedure described in the synthesis of
(1R,2S)-2, the desired (1S,2R)-2 was obtained in 87%
yield as a white solid: mp 205±2068C; [a]2D0ˆ12.95
1
In summary, we have synthesized a series of highly effective
chiral amino phosphine phosphinite ligands for hydrogena-
tion of dehydroamino acid precursors. The excellent
enantioselectivity in preparation of both (R)- and (S)-
amino acids with (1S,2R)- or (1R,2S)-isomer of DPAMPP
means a breakthrough in developing aminophosphine phos-
phinite ligands for asymmetric catalytic reaction. Moreover,
the high catalytic activity and enantioselctivity combined
with facile preparation for chiral DPAMPP indicates their
wide potential application in asymmetric synthesis.
(0.52, EtOH); H NMR (DMSO) d 4.77 (d, Jˆ6.8 Hz, 1H,
OCH), 5.01 (dd, J1ˆ6.8 Hz, J2ˆ9.3 Hz, 1H, NCH), 7.17±
7.33 (m, 10H, 2£Ph), 7.89 (s, 1H, HCO), 8.57 (d, Jˆ9.3 Hz,
1H, CONH).
(1S,2S)-1,2-Diphenyl-2-aminoethanol, (1S,2S)-1. Thionyl
chloride (7.8 mL, 107 mmol) was added to (1R,2S)-2 (3.6 g,
14.9 mmol) at 2158C. After stirring at 2158C for 3 h and
then at room temperature for additional 10 h, 50 mL of
cooled water was added. The resulted solution was re¯uxed
for 3 h followed by neutralization with 14 mL of 50%
NaOH. The precipitated product was collected by ®ltration
and further puri®ed by recrystallization from ethanol to give
2.6 g (88% yield) of (1S,2S)-1 as a white needle crystalline
solid: mp 123±1248C; [a]2D0ˆ2131.4 (0.87, EtOH);
Experimental
General aspects
n
max(KBr) 3360, 3080, 2900, 1450 cm21 1H NMR
;
(CDCl3) d 3.27 (br s, 3H, NH2, OH), 4.14 (d, Jˆ7.3 Hz,
1H, NCH), 4.74 (d, Jˆ7.3 Hz, 1H, OCH), 7.14±7.26 (m,
10H, 2£Ph); Anal. Calcd for C14H15NO: C, 78.84; H, 7.09;
N, 6.57. Found: C, 78.90; H, 6.95; N, 6.55.
All melting points were determined on a digital melting
1
point apparatus and were uncorrected. H NMR and 31P
NMR spectra were recorded on Brucker AC-200 and
Brucker AC-400 spectrometers. Elemental analyses were
performed on a Carlo Erba-1106 instrument. Infrared spec-
tra were recorded on a Nicolet MX-1 spectrometer. Optical
rotations were measured on a Perkin±Elmer 241 polari-
meter. All reactions involving air- and moisture-sensitive
compounds were carried out under a dry argon atmosphere
using standard Schlenk line techniques. THF, benzene and
triethylamine were distilled from sodium benzophenone
(1S,2S)-1,2-Diphenyl-2-formamidoethanol, (1S,2S)-2. The
desired (1S,2S)-2 was prepared using the same procedure
described for the synthesis of (1R,2S)-2. The crude product
was puri®ed by ¯ash chromatography on silica gel eluted
with chloroform/methanol (9:1) to give 51% yield as a white
needle crystalline solid: mp 127±1288C; [a]2D0ˆ16.1 (0.26,
1
EtOH); nmax(KBr) 3320, 3040, 1660, 1530, 1400 cm21; H

5862
R. Lou et al. / Tetrahedron 56 (2000) 5857±5863
NMR (CDCl3) d 5.04 (d, Jˆ4.0 Hz, 1H, OCH), 5.30 (dd,
J1ˆ3.9 Hz, J2ˆ7.9 Hz, 1H, NCH), 6.52 (d, Jˆ7.1 Hz, 1H,
CONH), 7.10±7.36 (m, 10H, 2£Ph), 8.19 (s, 1H, HCO);
Anal. Calcd for C15H15NO2: C, 74.67; H, 6.27; N, 5.80.
Found: C, 74.38; H, 6.25; N, 5.66.
128.4, 128.6, 128.7, 128.8, 129.1, 129.2, 129.4, 129.5,
129.6, 130.8, 131.0, 131.2, 132.4, 132.6, 132.8, 139.3,
139.4, 140.5, 141.3, 142.3, 142.4, 142.9, 143.1; Anal.
Calcd for C39H35NOP2: C, 78.64; H, 5.92; N, 2.35; P,
10.40. Found: C, 78.51; H, 5.78; N, 2.32; P, 9.94.
(1R,2S)-1,2-Diphenyl-2-(N-methyl)aminoethanol, (1R,2S)-
3. 12 mL of 1.5 M BH3/THF (18 mmol) was added slowly
to the solution of (1R,2S)-2 (0.93 g, 3.86 mmol) in
anhydrous THF (10 mL) at 08C. After stirring for 24 h at
room temperature, the reaction was quenched with methanol
and 3 N HCl. THF was distilled in vaccum, and the residue
was neutralized with 40% NaOH followed by extraction
with chloroform (10 mL£3). The combined organic phase
was washed with brine, dried over anhydrous MgSO4. After
removal of the solvent, the crude was recrystallized from
petroleum (bp 60±908C) to give 0.73 g (83% yield) of white
needle crystalline solid: mp 135±1378C; [a]2D0ˆ231.6
(1S,2R)-N,O-bis(diphenylphosphino)-1,2-diphenyl-2-(N-
methyl)aminoethanol, (1S,2R)-DPAMPP. With the simi-
lar procedure described in the synthesis of (1R,2S)-
DPAMPP, (1S,2R)-DPAMPP was prepared in 54% yield
as a white crystalline solid: mp 94±968C; [a]2D0ˆ137.6
31P NMR (CDCl3) d 65.9 (s, P(N)), 113.3 (s, P(O)); 1H NMR
(CDCl3) d 2.21 (d, JP±Hˆ2.4 Hz, 3H, CH3), 4.94 (dd,
JH±Hˆ10.0 Hz, JP±Hˆ14.4 Hz, 1H, NCH), 5.57 (dd,
JH±Hˆ10.4 Hz, JP±Hˆ8.4 Hz, 1H, OCH), 6.53±7.74 (m,
30H, 6£Ph); Anal. Calcd for C39H35NOP2: C, 78.64; H,
5.92; N, 2.35; P, 10.40. Found: C, 78.50; H, 5.90; N, 2.64;
P, 10.02.
(0.22, benzene); nmax (KBr) 3410, 3050, 2920, 1430 cm21
;
1
(0.42, EtOH); nmax(KBr): 3310 cm21; H NMR (CDCl3) d
2.27 (s, 3H, CH3), 3.76 (d, Jˆ5.9 Hz, 1H, NCH), 4.80 (d,
Jˆ5.9 Hz, 1H, OCH), 7.11±7.28 (m, 10H, 2£Ph). Anal.
Calcd for C15H17NO: C, 79.26; H, 7.54; N, 6.16. Found:
C, 79.63; H, 7.47; N, 6.15.
(1S,2S)-N,O-bis(diphenylphosphino)-1,2-diphenyl-2-(N-
methyl)aminoethanol, (1S,2S)-DPAMPP. With the simi-
lar procedure described in the synthesis of (1R,2S)-
DPAMPP, (1S,2S)-DPAMPP was prepared in 66% yield
as a white solid: mp 148±1508C; [a]2D0ˆ246.5 (0.17,
(1S,2R)-1,2-Diphenyl-2-(N-methyl)aminoethanol, (1S,2R)-
3. With the same procedure described for the synthesis of
(1R,2S)-3, compound (1S,2R)-3 was prepared in 91.0%
yield as a white needle crystalline solid: mp 135±1368C;
benzene); nmax(KBr) 3450, 3060, 2960, 1435 cm21
;
31P
1
NMR (CDCl3) d 63.7 (s, P(N)), 106.3 (s, P(O)); H NMR
(CDCl3) d 2.42 (d, JP±Hˆ2.4 Hz, 3H, CH3), 4.86 (dd,
JH±Hˆ10.0 Hz, JP±Hˆ10.4 Hz, 1H, NCH), 5.39 (dd,
JH±Hˆ9.2 Hz, JP±Hˆ6.8 Hz, 1H, OCH), 6.90±7.78 (m,
30H, 6£Ph); Anal. Calcd for C39H35NOP2: C, 78.64; H,
5.92; N, 2.35; P, 10.40. Found: C, 78.39; H, 5.85; N, 2.71;
P, 9.90
1
[a]2D0ˆ132.8 (0.50, EtOH); H NMR (CDCl3) d 2.28 (s,
3H, CH3), 3.78 (d, Jˆ5.8 Hz, 1H, NCH), 4.82 (d,
Jˆ6.0 Hz, 1H, OCH), 7.10±7.30 (m, 10H, 2£Ph). Anal.
Calcd for C15H17NO: C, 79.26; H, 7.54; N, 6.16. Found:
C, 79.50; H, 7.45; N, 6.25.
(1S,2S)-1,2-Diphenyl-2-(N-methyl)aminoethanol, (1S,2S)-
3. With the similar procedure described in the synthesis of
(1R,2S)-3, compound (1S,2R)-3 was prepared in 80% yield
as a white needle crystalline solid: mp 125±1268C;
[a]2D0ˆ2115.8 (0.34, EtOH); nmax(KBr) 3320, 3040, 1660,
A general procedure for asymmetric hydrogenation
catalyzed by cationic Rh complex
The cationic Rh catalyst was prepared in situ by stirring the
mixture of [Rh(COD)Cl]2, AgBF4 and an appropriate chiral
DPAMPP in THF for 2 h. The resulting cationic catalyst
was characterized by 31P NMR (for example, 31P NMR
(CD2Cl2) of [((1R,2S)-DPAMPP)Rh(COD)]BF4: d 72.4
(dd, JP(O)±P(N)ˆ653.8 Hz, JRh±P(N)ˆ334.4 Hz, P(N)), 138.0
(dd, JP(N)±P(O)ˆ653.2 Hz, JRh±P(O)ˆ397.0 Hz, P(O))). In a
stainless steel autoclave, a dehydroamino acid derivative
1
1530, 1400 cm21; H NMR (CDCl3) d 2.32 (s, 3H, CH3),
3.51 (d, Jˆ8.6 Hz, 1H, NCH), 4.60 (d, Jˆ8.6 Hz, 1H,
OCH), 7.01±7.26 (m, 10H, 2£Ph); Anal. Calcd for
C15H17NO: C, 79.26; H, 7.54; N, 6.16. Found: C, 79.71;
H, 7.59; N, 6.02.
(1R,2S)-N,O-bis(diphenylphosphino)-1,2-diphenyl-2-(N-
methyl)aminoethanol, (1R,2S)-DPAMPP. (1R,2S)-3
(100 mg, 0.44 mmol) and triethylamine (0.13 mL,
0.90 mmol) were dissolved in 3 mL of anhydrous benzene.
(0.02 mmol) was dissolved in
a degassed solvent
(0.4 mL). To the solution was add the prepared catalyst
(0.0002 mmol). The reactor was then pressurized with
hydrogen and the reaction was run under the chosen condi-
tions and determined by GC on a Chrompack Chirasil-L-Val
column or by HPLC on a Chiralcel OD column.
A
solution of chlorodiphenylphosphine (0.16 mL,
0.90 mmol) in benzene (1 mL) was added dropwise to the
mixture at 08C. After stirring at room temperature for 24 h,
the formed triethylammonium chloride was removed by
®ltration, and the obtained ®ltrate was puri®ed directly by
¯ash column chromatography on silica gel eluted with ben-
zene to give 140 mg (54% yield) of (1R,2S)-DPAMPP as a
white crystalline solid: mp 91±938C; [a]2D0ˆ233.1 (0.28,
Acknowledgements
benzene); nmax (KBr) 3400, 3040, 2910, 1430 cm21
;
31P
We thank the National Natural Science Foundation of China
(No. 29790124, 29972040) and Union Laboratory of Asym-
metric Synthesis in Chengdu for ®nancial support of this
study. We also thank Dr Dequn Sun for her gift of methyl
(Z)-2-benzamindo-3-(20-chloro-30-acetoxy-40-methoxyphenyl)-
acrylate.
1
NMR (CDCl3) d 64.8 (s, P(N)), 111.8 (s, P(O)); H NMR
(CD2Cl2) d 2.21 (d, JP±Hˆ2.5 Hz, 3H, CH3), 4.94 (dd,
JH±Hˆ10.4 Hz, JP±Hˆ14.2 Hz, 1H, NCH), 5.57 (dd,
JH±Hˆ10.1 Hz, JP±Hˆ8.3 Hz, 1H, OCH), 6.53±7.52 (m,
30H, 6£Ph); 13C NMR (CD2Cl2) d 33.6, 75.1, 83.5, 128.0,

R. Lou et al. / Tetrahedron 56 (2000) 5857±5863
5863
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