Highly rigid diphosphane ligands with a large dihedral angle based on a chiral spirobifluorene backbone

Article abstract of DOI:10.1002/anie.200462072

High and wide: The high rigidity and large dihedral angle of chiral, spirobifluorene-based diphosphane ligands lead to excellent reactivity and enantioselectivity in the ruthenium-catalyzed asymmetric hydrogenation of α,β-unsaturated carboxylic acids (see scheme).

Full text of DOI:10.1002/anie.200462072

Communications
Asymmetric Catalysis
Highly Rigid Diphosphane Ligands with a Large
Dihedral Angle Based on a Chiral Spirobifluorene
Backbone**
Xu Cheng, Qi Zhang, Jian-Hua Xie, Li-Xin Wang, and
Qi-Lin Zhou*
Asymmetric catalysis is undoubtedly a powerful, econom-
ically feasible tool for the synthesis of optically active organic
compounds both in the laboratory and on a production scale.
The design and synthesis of chiral phosphane ligands have
played a significant role in the development of efficient,
transition-metal-catalyzed asymmetric reactions.[1] In the last
decades, a large number of chiral diphosphane ligands, such as
diop,[2] binap,[3] josiphos,[4] duphos,[5] pennphos,[6] bisp,[7] p-
phos,[8] and tangphos,[9] have been prepared and used in
asymmetric catalysis with excellent enantioselectivities. Since
there are no universal ligands and catalysts for asymmetric
transformations, and most asymmetric reactions are substrate
dependent, the search for chiral ligands that are more
efficient in terms of high enantioselectivity and high turnover
number (TON) remains one of the most important goals in
asymmetric catalysis.
Although many structural features should be taken into
consideration in the design of new chiral ligands, a certain
degree of rigidity of the ligand and catalyst has been shown to
be one of the most significant factors for obtaining high
enantioselectivity.[10] For instance, in the “privileged” chiral
catalysts containing a binap ligand, the highly rigid, atropiso-
meric, C2-symmetric binaphthyl structure fixes the conforma-
tion of the seven-membered heterometallocyclic ring of its
metal complexes and determines the orientations of the P-
phenyl groups, which ultimately exert steric influence on the
binding substrate.[11] As modifications of binap, a number of
diphosphane ligands with a narrower dihedral angle have
been designed, for example biphemp,[12] segphos,[13] tuna-
phos,[14] synphos,[15] and naphephos,[16] which have provided a
better enantiocontrol in several well-established catalytic
reactions.[17] In contrast, ligands with a wider dihedral angle
than that of binap have rarely been explored.[18] Herein we
report the synthesis of the new spirobifluorene-based diphos-
phane ligands (SFDPs) 1 with an extremely high rigidity and
[*] X. Cheng, Q. Zhang, Dr. J.-H. Xie, Prof. L.-X. Wang, Prof. Q.-L. Zhou
State Key Laboratory and
Institute of Elemento-organic Chemistry
Nankai University
Tianjin 300071 (China)
Fax: (+86)222-350-6177
E-mail: qlzhou@nankai.edu.cn
[**] We thank the National Natural Science Foundation of China, the
Major Basic Research Development Program (Grant
G2000077506), the Ministry of Education of China, and the
Committee of Science and Technology of Tianjin for financial
support.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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DOI: 10.1002/anie.200462072
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Angewandte
Chemie
large dihedral angle based on a spirobifluorene backbone, the
structural characterization of a Pd complex, and their
application in ruthenium-catalyzed asymmetric hydrogena-
tion of a,b-unsaturated carboxylic acid, with high activity and
excellent enantioselectivity.
While molecules with a 9,9’-spirobifluorene structure have
been widely applied in molecular electronics,[19] light-emitting
materials,[20] enantioselective molecular recognition,[21] and
other areas,[22] the use of chiral ligands with a 9,9’-spirobi-
fluorene backbone for asymmetric catalysis has not yet been
reported. Recently, we reported the synthesis of optically
pure 9,9’-spirobifluorene-1,1’-diol (SBFOL, 2).[23] The diphos-
phane ligands 1 can be synthesized from SBFOL. Thus, (R)-
(2) was first converted into the ditriflate (R)-3 in quantitative
yield. This compound was then directly subjected to diphos-
phanylation with diarylphosphanes in the presence of a nickel
catalyst following the method of Cai et al.[24] for the synthesis
of binap, although no coupling reaction occurred. We there-
fore attempted Hayashiꢀs stepwise strategy[25] to introduce
phosphanyl groups and found that it works nicely. Mono-
phosphanylation of ditriflate (R)-3 with diarylphosphane oxide
in the presence of a Pd complex of dppb, followed by reduction
with trichlorosilane, generated (R)-1-(diarylphosphanyl)-1’-
trifluoromethanesulfonyloxy-9,9’-spirobifluorene ((R)-5). The
second diarylphosphanyl group was introduced by repeating
the above two-step protocol. The target diphosphanes (R)-1
were obtained in 50–60% overall yield (Scheme 1). Following
the same procedure, the diphosphanes (S)-1 were also
synthesized from (S)-9,9’-spirobifluorene-1,1’-diol.
Figure 1. Crystal structure of [PdCl2((R)-1a)]. Solvent and hydrogen
atoms have been omitted for clarity.
greater than that of [PdCl2((R)-binap)] (92.78).[11c] In addition,
one P-phenyl group on each phosphorus atom lies parallel to
the fluorene ring of the bifluorene moiety; the distances
between the centers of the P-phenyl rings and the benzo rings
of bifluorene are 3.5 and 3.6 ꢁ, respectively, thereby indicating
p–p stacking interactions between the P-phenyl rings and the
A crystal of the complex [PdCl2((R)-1a)] suitable for X-
ray diffraction was grown and analyzed.[26] As can be seen
from Figure 1, the complex has a square-planar configuration
and the eight-membered heterometallocyclic ring formed by
the chelate coordination of SFDP to palladium is highly rigid.
The perpendicular spirobifluorene structure is distorted: in
[PdCl2((R)-1a)], the P-Pd-P bite angle is 96.78, which is
fluorenes, as also observed in [PdCl2((R)-binap)].[11c] The Pd P
À
À
(2.28 and 2.30 ꢁ) and Pd Cl (2.33 and 2.36 ꢁ) bond lengths in
[PdCl2((R)-1a)] are in the typical range for dichloropalladium
complexes bearing diphosphane ligands.[27]
The efficiency of the chiral SFDP ligands in the enantio-
selective, ruthenium-catalyzed hydrogenation of a,b-unsatu-
rated carboxylic acids, which is a very useful reaction in
organic and industrial synthesis, was investigated.[28] The
catalysts
7
were prepared as red powders from
[{RuCl2(C6H6)}2] and 1 in DMF followed by the addition of
NaOAc (Scheme 2).[29] The catalysts [Ru(OAc)2((R)-1)] ((R)-
7) show a single resonance signal in their 31P NMR spectra
(d = 64–67 ppm).
Although significant progress has been achieved in
asymmetric hydrogenation of a-arylacrylic acid and other
a,b-unsaturated carboxylic acids,[8,30] the asymmetric hydro-
genation of cinnamic acid derivatives is still a challenge.[30c,31]
The catalyst [Ru(OAc)2((R)-1a)] ((R)-7a) was initially tested
in the hydrogenation of a-methylcinnamic acid at a substrate-
Scheme 1. Synthesis of ligands 1: a) Tf2O, pyridine, CH2Cl2, À158C,
3 h; b) Pd(OAc)2 (5 mol%), dppb (5 mol%), iPr2EtN, Ar2POH, DMSO,
1008C, 1 h; c) HSiCl3, iPr2EtN, toluene, 1108C, 8 h.
Scheme 2. Preparation of catalysts [Ru(OAc)2((R)-1)] ((R)-7)):
a) [{RuCl2(C6H6)}2] (0.56 equiv.), DMF; b) NaOAc (10 equiv.), MeOH.
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Communications
Table 2: Asymmetric hydrogenation of tiglic acid derivatives.[a]
to-catalyst (S/C) ratio of 400 in MeOH under 6 atm of H2 at
room temperature over 48 h. The hydrogenation product a-
methylhydrocinnamic acid was obtained in 93% yield with
60% ee (Table 1, entry 1). This result is better than that
Entry
R1
R2
Cat.
t [h]
Yield [%]
ee [%][b]
Table 1: Asymmetric hydrogenation of a-methylcinnamic acid
1
2
3
4
5
Me
Me
Me
Me
Me
Me
Me
Et
nPr
nPr
nBu
iBu
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
(R)-7a
(R)-7b
(R)-7c
(R)-7d
(R)-7e
(R)-7d
(R)-7d
(R)-7d
(R)-7d
(R)-7d
(R)-7d
(R)-7d
16
16
16
16
12
30
100
24
30
40
35
40
92
85
91
92
85
90
94
94
91
82
92
88
96
96
94
97
97
98
98
96
96
94
96
97
derivatives.[a]
6[c]
7[d]
8
Entry
R
Cat.
t [h]
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
H
H
H
H
(R)-7a
(R)-7b
(R)-7c
(R)-7d
(R)-7e
(R)-7e
(R)-7e
(R)-7e
(R)-7e
(R)-7e
(R)-7e
(R)-7e
(R)-7e
(R)-7e
(R)-7e
(R)-7e
(R)-7e
(R)-7e
(R)-7e
(R)-7e
48
48
30
24
18
22
20
22
25
20
24
10
12
9
12
12
9
8
30
18
93
89
91
93
91
93
93
91
91
92
90
91
94
90
90
93
90
94
93
95
60
45
70
87
94
90
97
95
94
94
94
94
92
93
95
95
92
92
92
93
9
10
11
12
Me
Me
H
p-Me
m-Me
o-Me
p-OMe
m-OMe
o-OMe
p-Cl
m-Cl
o-Cl
m-Br
o-Br
[a] Conditions: see footnote [a] in Table 1. [b] ee was determined by HPLC
analysis of the respective anilide with a chiral column (AD-H); the
predominant configuration is
S for all products. [c] [substrate]=
0.625 molLÀ1, S/C=1000. [d] [substrate]=6.25 molLÀ1, S/C=10000,
508C.
In conclusion, SFDP, a new type of highly rigid diphos-
phane ligands with a large dihedral angle, has been synthe-
sized based on a chiral spirobifluorene backbone. Their
ruthenium complexes are highly efficient catalysts for asym-
metric hydrogenation of a,b-unsaturated carboxylic acids.
The excellent activity and enantioselectivity of these ruthe-
nium complexes in the hydrogenation of a-methylcinnamic
acid derivatives and tiglic acid derivatives indicate that these
highly rigid ligands might be more widely applicable in
asymmetric catalytic reactions.
p-CF3
o-CF3
o-NO2
2-naphth
[a] Conditions: [substrate]=0.25 molLÀ1 in MeOH, S/C=400, p
=
H2
6 atm, T=25–288C. [b] Conversions were quantitative for all reactions.
All hydrogenated products were fully characterized (see Supporting
Information). [c] ee was determined by HPLC analysis of the respective
Received: September 22, 2004
Revised: November 25, 2004
anilide with
a chiral column (see Supporting Information). The
predominant configuration of a-methylhydrocinnamic acid is S. All
other saturated acids have positive rotations.
Keywords: asymmetric catalysis · chirality · hydrogenation ·
phosphines · spirobifluorenes
.
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activity and enantioselectivity of the catalyst (18 h, 94% ee;
Table 1, entry 5). A variety of a-methylcinnamic acid deriv-
atives were hydrogenated under these mild conditions using
catalyst (R)-7e with excellent enantioselectivities. The results
summarized in Table 1 represent the highest enantioselectiv-
ity yet achieved in the asymmetric hydrogenation of a-
methylcinnamic acid.[30c,31]
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