Rh-catalyzed asymmetric hydrogenation by using a new family of C2-symmetric bisphosphinites and a bisaminophosphine as ligands

Article abstract of DOI:10.1016/S0040-4039(00)02358-3

The application of a new family of four-chiral-centered C₂-symmetric bisphosphinites (1, 2 and 3) and the bisaminophosphine 4 in Rh-catalyzed asymmetric hydrogenation of dehydroamino acids has been examined. Up to 98% ee was obtained in the hydrogenation of α-acetamidocinnamic acid, which is comparable with the enantioselection obtained from the best chiral bisphosphinites and bisaminophosphines.

Full text of DOI:10.1016/S0040-4039(00)02358-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 1761–1763
Rh-catalyzed asymmetric hydrogenation by using a new family
of C -symmetric bisphosphinites and a bisaminophosphine as
2
ligands
Ao Zhang and Biao Jiang*
Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai 200032, PR China
Received 25 October 2000; revised 11 December 2000; accepted 21 December 2000
Abstract—The application of a new family of four-chiral-centered C -symmetric bisphosphinites (1, 2 and 3) and the
2
bisaminophosphine 4 in Rh-catalyzed asymmetric hydrogenation of dehydroamino acids has been examined. Up to 98% ee was
obtained in the hydrogenation of a-acetamidocinnamic acid, which is comparable with the enantioselection obtained from the best
chiral bisphosphinites and bisaminophosphines. © 2001 Elsevier Science Ltd. All rights reserved.
Transition metal-catalyzed asymmetric synthesis and
reactions have been recognized as the most fruitful and
efficient methods for preparing optically active sub-
stances. To achieve high stereoselection, it is crucial to
design and prepare efficient chiral ligands. Up to now,
become a prototype for evaluation of new chiral diphos-
phine catalysts. In contrast to many chiral diphosphines
reported in the literature, chiral phosphinites employed
in transition metal-catalyzed asymmetric reactions are
generally recognized as poor ligands with few excep-
1
7
a large number of monodentate, C -symmetric or
tions, due to their lower electron donating ability and
2
pseudo C -symmetric bidentate and multidentate lig-
increased conformational flexibility relative to phosphi-
2
8
8d
ands have been widely reported in a variety of catalytic
nes. In recent years, Selke and RajanBabu have
reported the use of a series of chiral phosphinite ligands
derived from natural chiral pools (e.g. carbohydrates
and tartaric acids) to give good to excellent results in
1
–3
asymmetric reactions. Amongst these, optically active
diphosphine ligands (e.g. BINAP, DIOP, BDPP,
DUPHOS, CHIRAPHOS and BICP) with C -symmetry
2
9
have been well documented as being able to create
effective chiral environments for substrates and nucle-
rhodium-catalyzed asymmetric hydrogenation. Zhang
10
and Chan also reported that rhodium complexes bear-
ing (R)- or (S)-spiro phosphinite ligands are highly
effective in the enantioselective hydrogenation of dehy-
droamino acids and their esters. Very recently,
bisaminophosphines were also found to be effective
ligands for catalytic hydrogenation reactions leading to
chiral amino acids, but only a limited number of
4
ophiles, and they have been widely employed in a large
number of transition metal-catalyzed reactions, espe-
cially in the rhodium-catalyzed asymmetric hydrogena-
1
,5
tion of prochiral dehydroprecursors.
In fact,
asymmetric hydrogenation is one of the most practical
methods in asymmetric synthesis, accounting for 70% of
6
11
all procedures used on a commercial scale, and it has
bisaminophosphines have been investigated.
Scheme 1.
*
0
Corresponding author. Tel.: 86-21-64163300; fax: 86-21-64166128; e-mail: jiangb@pub.sioc.ac.cn
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)02358-3

1
762
A. Zhang, B. Jiang / Tetrahedron Letters 42 (2001) 1761–1763
a
Table 1. Rh-catalyzed asymmetric hydrogenation of dehydroamino acid derivatives
Entry
Ligand
Substrate
Yield (%)
Ee (%)b
1
2
3
4
5
6
7
8
9
1
2
3
4
1
2
3
4
1
4
R=H, R%=Me
R=H, R%=Me
R=H, R%=Me
R=H, R%=Me
R=Ph, R%=H
R=Ph, R%=H
R=Ph, R%=H
R=Ph, R%=H
R=4-MeOPh, R%=Me
R=4-MeOPh, R%=Me
72
77
80
77
98
94
98
99
97
99
41
46
48
68
94
89
97
98
90
91
c
c
c
c
1
0
a
b
c
The reactions were performed at room temperature under 1 atm of H2 for 24 h: [substrate/[Rh(COD) ]BF /ligand=1:0.01:0.011].
Determined by HPLC using Chiralcel AD or OJ columns.
The ee value was determined after converting the products to the corresponding methyl ester.
2
4
In the course of our studies in the field of asymmetric
synthesis and reactions, we have developed a new fam-
strates significantly affected the catalytic activity and
enantioselectivity in our system. There are four stereo-
genic carbon centers in our ligand system and the
absolute configuration of the four stereogenic carbon
centers dictate the orientation of the four P-phenyl
ily of C -symmetric bisphosphinites 1, 2 and 3 and
2
bisaminophosphine 4, which have proven to be good
12
ligands in asymmetric allylic substitution. To probe
further the potential of this family in asymmetric reac-
tions, we have investigated their efficiency in asymmet-
ric hydrogenation. Here are the preliminary results
9,10,13
groups similar to Zhang and Chan’s results.
For
the bisphosphinites 1, 2 and 3, a seven-membered lig-
and–Rh complex was formed, while a nine-membered
(
Scheme 1).
ligand–Rh
complex
was
the
product
from
bisaminophosphine 4. The high enantioselectivities for
the two kinds of ligand–Rh complexes in the hydro-
genation of a-acetamidocinnamic acid suggest a ratio-
nal matching of the catalyst chiral environment with
the substrate. The low enantioselectivity in the hydro-
genation of methyl a-acetamidoacrylate was attributed
to less bulky substituents in the substrate compared to
the a-acetamidocinnamic acid. Further exploitation of
the relationship between the catalyst and substrate are
ongoing.
First, we chose the often employed substrate, methyl
a-acetamidoacrylate, as the model. The asymmetric
hydrogenation was performed at ambient temperature
with 1 atm of hydrogen in the presence of the Rh
catalyst, which was formed in situ by mixing
[
Rh(COD) ]BF with 1.1 mol. equiv. of the ligand
2 4
under an inert atmosphere. Entries 1–4 in Table 1
summarize the results of asymmetric hydrogenation
employing our new ligands. The reaction was carried
out in propan-2-ol with good yields and moderate
stereoselection (41–48% ee) when phosphinites 1–3 were
used as the ligand, whilst up to 68% ee was obtained in
the case of bisaminophosphine 4.
In summary, the application of the new family of
four-chiral-centered C -symmetric bisphosphinites 1, 2
2
and 3 and the bisaminophosphine 4 in Rh-catalyzed
asymmetric hydrogenation of dehydroamino acids has
been studied. Up to a 98% ee was obtained in the
hydrogenation of a-acetamidocinnamic acid, while only
moderate enantioselectivity was observed in the case of
methyl a-acetamidoacrylate. Our results for the asym-
metric hydrogenation of acetamidocinnamic acid are
comparable with the enantioselection obtained from the
best chiral bisphosphinites and bisaminophosphines.
We then tested the stereoselection by using a-acetami-
docinnamic acid as the hydrogenation substrate. Under
the same conditions we found that the C -symmetric
2
bisphosphinites 1 and 3 gave ees of 94 and 97%,
respectively (entries 5 and 7), and the bisphosphinite 2
gave a slightly lower ee of 89% (entry 6). The highest
enantioselectivity of 98% (entry 8) was obtained by
using bisaminophosphine 4 as the ligand.
Finally, we chose an a-acetamidocinnamic ester with a
methoxy substituent in the 4-position of the phenyl ring
as the substrate. Up to a 90% ee was achieved with
phosphinite 1 and bisaminophosphine 4 as the ligands
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