Novel C2-symmetric planar chiral diphosphine ligands and their application in Pd-catalyzed asymmetric allylic substitutions

Article abstract of DOI:10.1021/jo0711440

(Chemical Equation Presented) Novel C₂-symmetric diphosphine ligands possessing only the planar chirality of ruthenocene, 1,1′-bis(diphenylphosphino)-2,2′-disubstituted-ruthenocenes (4), were prepared. With this kind of ligands, excellent enant

Full text of DOI:10.1021/jo0711440

Novel C -Symmetric Planar Chiral Diphosphine Ligands and Their
2
Application in Pd-Catalyzed Asymmetric Allylic Substitutions
Delong Liu, Fang Xie, and Wanbin Zhang*
School of Chemistry and Chemical Technology, Shanghai Jiao Tong UniVersity, 800 Dongchuan Road,
Shanghai 200240, People’s Republic of China
wanbin@sjtu.edu.cn
ReceiVed June 1, 2007
Novel C
2
-symmetric diphosphine ligands possessing only the planar chirality of ruthenocene, 1,1′-bis-
(diphenylphosphino)-2,2′-disubstituted-ruthenocenes (4), were prepared. With this kind of ligands, excellent
enantioselectivity and especially highly catalytic activity in palladium-catalyzed asymmetric allylic
substitutions of rac-1,3-diphenyl-2-propenyl acetate (9) were observed, compared to their ferrocene
analogues 1. Good enantioselectivity and highly catalytic activity were also obtained with 4 in palladium-
catalyzed asymmetric allylic substitutions of cyclohexen-1-yl acetate (12). Further study on the effect of
R in ester group on enantioselectivity of 4 showed an opposite trend compared with their ferrocene
analogues 1 in asymmetric allylic substitutions. For ruthenocene ligands 4, the one with the smaller R in
the ester group gave higher enantioselectivity for the palladium-catalyzed asymmetric allylic substitutions
of 9, while a converse trend had been observed with 1. However, for the palladium-catalyzed asymmetric
allylic substitutions of 12, ligand 4 with a larger R in the ester group resulted in somewhat higher
enantioselectivity but still an opposite trend with ligand 1. The X-ray diffraction study of crystal structures
of 4 and 1 with Pd(II) was carried out and showed that the enantioselectivity was correlated to the twist
angle existing in the palladium complex.
Introduction
Ferrocene-based planar chiral ligands have received intensive
attention, and many kinds of planar chiral ferrocene ligands have
been developed recently. Meanwhile, C2-symmetric chiral
In the last few decades, tremendous progress has been made
in the design of new chiral ligands for the development of
efficient metal-catalyzed asymmetric transformations. Of the
various chiral ligands reported, diphosphines are the most
popular in asymmetric catalysis, due mainly to their stability
3
1
(3) Selected reviews: (a) Hayashi, T. In Ferrocenes; Togni, A., Hayashi,
T., Eds.; VCH: Weinheim, Germany, 1995; p 105. (b) Colacot, T. J. Chem.
ReV. 2003, 103, 3101-3118. (c) Dai, L. X.; Tu. T.; You, S. L.; Deng, W.
P.; Hou, X. L. Acc. Chem. Res. 2003, 36, 659-667. (d) Atkinson, R. C. J.;
Gibson, V. C.; Long, N. J. Chem. Soc. ReV. 2004, 33, 313-328. (e) Ramon,
G. A.; Javier, A.; Juan, C. C. Angew. Chem., Int. Ed. 2006, 45, 7674-
and outstanding ability to form highly active and selective
complexes with transition metals.2
7715. Selected papers: (f) Zhang, W.; Adachi, Y.; Hirao, T.; Ikeda, I.
Tetrahedron: Asymmetry 1996, 7, 451-460. (g) Zhang, W.; Hirao, T.; Ikeda,
I. Tetrahedron Lett. 1996, 37, 4545-4548. (h) Riant, O.; Argouarch, G.;
Guillaneux, D.; Samuel, O.; Kagan, H. B. J. Org. Chem. 1998, 63, 3511-
3514. (i) Imai, Y.; Zhang, W.; Kida, T.; Nakatsuji, Y.; Ikeda, I. Chem.
Lett. 1999, 243-244. (j) Zhang, W.; Yoshinaga, H.; Imai, Y.; Kida, T.;
Nakatsuji, Y.; Ikeda, I. Synlett 2000, 1512-1514. (k) Bolm, C.; Rudolph,
J. J. Am. Chem. Soc. 2002, 124, 14850-14851. (l) Matsumura, S.; Maeda,
Y.; Nishimura, T.; Uemura, S. J. Am. Chem. Soc. 2003, 125, 8862-8869.
(m) Roca, F. X.; Motevalli, M.; Richards, C. J. J. Am. Chem. Soc. 2005,
127, 2388-2389. (n) Ogasawara, M.; Ito, A.; Yoshida, K.; Hayashi, T.
Organometallics 2006, 25, 2715-2718. (o) Hua, G. H.; Liu, D. L.; Xie,
F.; Zhang, W. Tetrahedron Lett. 2007, 48, 385-388.
*
Address correspondence to this author. Fax: +86 21 5474 3265. Phone:
86 21 5474 3265.
1) (a) Noyori, R. In Asymmetric Catalysis in Organic Synthesis;
+
(
Wiley: New York, 1994. (b) Ohkuma, T.; Kitamura, M.; Noyori, R. In
Catalytic Asymmetric Synthesis; Ojima, I., Ed.; Wiley-VCH: Weinheim,
Germany, 2000; p 1. (c) Brown, M. In ComprehensiVe Asymmetric
Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin,
Germany, 1999; p 121. (d) Helmchen, G.; Pfaltz, A. Acc. Chem. Res. 2000,
3
3, 336-345.
2) (a) McCarthy, M.; Guiry, P. J. Tetrahedron 2001, 57, 3809-3844.
b) Tang, W.; Zhang, X. Chem. ReV. 2003, 103, 3029-3069.
(
(
10.1021/jo0711440 CCC: $37.00 © 2007 American Chemical Society
6
992
J. Org. Chem. 2007, 72, 6992-6997
Published on Web 08/04/2007

2
NoVel C -Symmetric Planar Chiral Diphosphine Ligands
of novel ruthenocenediphosphine ligands 4 and their application
to Pd-catalyzed asymmetric allylic substitutions, by comparing
with their ferrocene analogues 1.
Results and Discussion
Synthesis of Ester Amide (4). Ligands 4 can be easily
6
c
prepared from 5 by the transformation of the oxazoline
moieties in the molecule by the method reported (Scheme 1).
FIGURE 1. Structure of 1 and 4 and their complexation with
palladium.
4e
Thus, treatment of 5 with trifluoroacetic acid in aqueous THF
caused ring-opening of the oxazoline moiety to give an unstable
ammonium salt. This ammonium salt was acetylated with acetic
anhydride without isolation in the presence of pyridine to give
ester amide 6 in 83% yield. Transesterification of 6 with
methanolic sodium methoxide at room temperature for 24 h gave
ligand 4a in 75% yield. Ligand 4b was also prepared from 6
by a similar procedure with a yield of 74%.
ferrocene ligands, especially those with only planar chirality,
have recently gained much attention since the pioneering
4
work reported by the Ikeda group. It was also known that an
asymmetric reaction environment such as dihedral angle in
some C2-symmetric axially chiral diphosphine ligands is es-
sential for attaining high enantioselectivity in asymmetric
Catalytic Test of Palladium-Catalyzed Asymmetric Allylic
Alkylation. With the novel C2-symmetric planar chiral P,P-
chelating ligands 4 in hand, we first tried to apply them in
palladium-catalyzed asymmetric allylic alkylation of rac-1,3-
diphenyl-2-propenyl acetate (9) with dimethyl malonate, which
is a classic substrate for many new kinds of ligands to test their
5
catalysis. During the development of the C2-symmetric planar
chiral ligands, we were interested to see if varying the twist
angle of the two Cp rings upon complexation of the ligands
with a metal would have an effect on the asymmetric catalytic
reaction (Figure 1).
It was reported that C2-symmetric planar chiral diphosphine
ferrocene ligands 1 were efficient for Pd-catalyzed asymmetric
allylic alkylation (Figure 1).4 When 1a was coordinated with
Pd(II), only configuration 2 of the complex was formed and no
7
asymmetric catalytic behavior. The results were summarized
in Table 1.
a,e
The influence of reaction conditions upon the allylic alky-
lation was taken into account. First of all, the effect of the
solvent on the catalytic reaction was examined with 4a (Table
3
was found at all. We conceived that the twist angle θ of 2
could have a nonneglectable effect on the catalytic activity and
enantioselectivity. On the one hand, θ could be changed via
changing metal atom Fe to Ru between the two Cp rings because
of the different distances of two Cp rings in ferrocene and
ruthenocene backbone. On the other hand, it could be also
changed by changing R′ groups on the Cp rings (Figure 1,
configuration 2). For this purpose we are interested in develop-
ing a new type of C2-symmetric planar chiral diphosphine
ruthenocene ligands. To the best of our knowledge, there are
1
, entries 1-5). Dichloromethane was selected as the best one
according to the chemical yield and the enantioselectivity. The
addition of NaOAc also affected the enantioselectivity. In the
absence of NaOAc, 83.6% ee was obtained and the enantiose-
lectivity was enhanced to 91.0% ee when it was used (Table 1,
entries 1 and 6). The temperature also affected the enantiose-
lectivity, and up to 95.7% ee was obtained at -25 °C with 4a
(
Table 1, entries 7-9). It was further shown that the R in the
ester group has an effect on this asymmetric synthesis with 4a
6
few reports on the development of chiral ruthenocene ligands.
Thus, we report herein the synthesis and crystal structure study
methyl ester leading to higher enantioselectivity compared with
4
b ethyl ester (Table 1, entries 8 and 10).
Compared with ferrocene ligands 1, much higher catalytic
(
4) (a) Zhang, W.; Kida, T.; Nakatsuji, Y.; Ikeda, I. Tetrahedron Lett.
activity was obtained with ruthenocene ligands 4 for this
asymmetric allylic alkylation. The reactions could be completed
within 30 min at room temperature in suitable solvents and not
more than 2 h even at -25 °C (Table 1, entries 8 and 10).
1
996, 37, 7995-7998. (b) Pye, P. J.; Rossen, K.; Reamer, R.; Tsou, N.;
Volante, R.; Reider, P. J. Am. Chem. Soc. 1997, 119, 6207-6208. (c) Kang,
J.; Lee, J. H.; Ahn, S. H.; Choi, J. S. Tetrahedron Lett. 1998, 39, 5523-
5
8
526. (d) Perea, J. A.; Borner, A.; Knochel, P. Tetrahedron Lett. 1998, 39,
073-8706. (e) Zhang, W.; Shimanuki, T.; Kida, T.; Nakatsuji, Y.; Ikeda,
I. J. Org. Chem. 1999, 64, 6247-6251. (f) Manfred, T.; Reetz, M. T.;
Beuttenmuller, R.; Mireia, P. Tetrahedron Lett. 1999, 40, 4977-4980. (g)
Zhang, W.; Yoneda, Y.-I.; Kida, T.; Nakatsuji, Y.; Ikeda, I. J. Organomet.
Chem. 1999, 574, 19-23. (h) Kang, J.; Lee, J. H.; Kim, G. J. Chirality
(7) Selected papers: (a) Trost, B. M.; Strege, P. E. J. Am. Chem. Soc.
1977, 99, 1649-1651. (b) Trost, B. M.; Murphy, D. J. Organometallics
1985, 4, 1143-1145. (c) Imai, Y.; Zhang, W.; Kida, T.; Nakatsuji, Y.; Ikeda,
I. Tetrahedron Lett. 1998, 39, 4343-4346. (d) Zhang, W.; Yoneda, Y.-I.;
Kida, T.; Nakatsuji, Y.; Ikeda, I. Tetrahedron: Asymmetry 1998, 9, 3371-
3380. (e) Imai, Y.; Zhang, W.; Kida, T.; Nakatsuji, Y.; Ikeda, I. Synlett
1999, 1319-1321. (f) Mino, T.; Shiotsuki, M.; Yamamoto, N.; Suenaga,
T.; Sakamoto, M.; Fujita, T.; Yamashita, M. J. Org. Chem. 2001, 66, 1795-
1797. (g) Trost, B. M.; Jiang, C. H. Org. Lett. 2003, 5, 1563-1565. (h)
Tanaka, Y.; Mino, T.; Akita, K.; Sakamoto, M.; Fujita, T. J. Org. Chem.
2004, 69, 6679-6687. (i) Pamies, O.; Dieguez, M.; Claver, C. J. Am. Chem.
Soc. 2005, 127, 3646-3647. (j) Polet, D.; Alexakis, A.; Tissot-Croset, K.;
Corminboeuf, C.; Ditrich, K. Chem. Eur. J. 2006, 12, 3596-3609. (k) Fur,
N. L.; Mojovic, L.; Ple, N.; Turck, A.; Reboul, V.; Metzner, P. J. Org.
Chem. 2006, 71, 2609-2616. (l) Kwong, H.-L.; Yeung, H.-L.; Lee, W.-S.;
Wong, W.-T. Chem. Commun. 2006, 4841-4843. (m) Fukuzumi, T.;
Shibata, N.; Sugiura, M.; Yasui, H.; Nakamura, S.; Toru, T. Angew. Chem.,
Int. Ed. 2006, 45, 4973-4977. (n) Raluy, E.; Claver, C.; Pamies, O.;
Dieguez, M. Org. Lett. 2007, 9, 49-52.
2
000, 12, 378-382. (i) Chieffi, A.; Comasseto, J. V.; Snieckus, V. Synlett
000, 2, 269-271. (j) Metallinos, C.; Szillat, H.; Taylor, N. J.; Snieckus,
2
V. AdV. Synth. Catal. 2003, 345, 370-382. (k) Ryoichi, K.; Takashi, U.;
Makoto, S.; Ito, Y. Tetrahedron: Asymmetry 2004, 15, 2263-2271.
(
5) (a) Harada, T.; Takeuchi, M.; Hatsuda, M.; Ueda, S. J.; Oku, A.
Tetrahedron: Asymmetry 1996, 7, 2479-2482. (b) Zhang, Z. G.; Qian, H.;
Longmire, J.; Zhang, X. M. J. Org. Chem. 2000, 65, 6223-6226. (c) Saito,
T.; Yokozawa, T.; Ishizaki, T.; Moroi, T.; Sayo, N.; Miura, T.; Kumoba-
yashi, H. AdV. Synth. Catal. 2001, 343, 264-267. (d) Duprat de Paule, S.;
Jeulin, S.; Ratovelomanana-Vidal, V.; Genet, J.-P.; Champion, N.; Dellis,
P. Eur. J. Org. Chem. 2003, 1931-1941. (e) Jeulin, S.; Duprat de Paule,
S.; Ratovelomanana-Vidal, V.; Genet, J.-P.; Champion, N.; Dellis, P. Angew.
Chem., Int. Ed. 2004, 43, 320-325. (f) Qiu, L.; Kwong, F. Y.; Wu, J.;
Lam, W. H.; Chan, S.; Yu, W.-Y.; Li, Y.-M.; Guo, R.; Zhou, Z.; Chan, A.
S. C. J. Am. Chem. Soc. 2006, 128, 5955-5965.
(6) (a) Hayashi, T.; Ohno, A.; Lu, S.-J.; Matsumoto, Y.; Fukuyo, E.;
Yanagi, K. J. Am. Chem. Soc. 1994, 116, 4221-4226. (b) Bolm, C.;
Hermanns, N.; Kesselgruber, M.; Hildebrand. J. Organomet. Chem. 2001,
(8) Wimmer, P.; Widhalm, M. Tetrahedron: Asymmetry 1995, 6, 657-
660.
6
4
24, 157-161. (c) Liu, D. L.; Xie, F.; Zhang, W. Tetrahedron Lett. 2007,
8, 585-588.
(9) Hayashi, T.; Yamamoto, A.; Ito, Y.; Nishioka, E.; Miura, H.; Yanagi,
K. J. Am. Chem. Soc. 1989, 111, 6301-6311.
J. Org. Chem, Vol. 72, No. 18, 2007 6993

Liu et al.
SCHEME 1. Synthesis of Ligands 4
TABLE 1. Allylic Substitution of 1,3-Diphenyl-2-propenyl Acetate
TABLE 2. Allylic Substitution of 1,3-Diphenyl-2-propenyl Acetate
with Benzylaminea
a
with Dimethyl Malonate
ee (%)b,c
yield (%)
/
entry
ligand
T/°C
time/h
solvent
ee (%)b,c/
entry
ligand
T/°C
t/h
solvent
yield (%)
1
2
3
4
5
4a
4a
4a
4a
4a
4a
4a
4a
4a
4b
1a
1b
1a
25
25
25
25
25
25
0
-25
-78
-25
25
0.5
0.5
0.5
4
8
0.5
1
2
7
2
1
CH2Cl2
DMF
CH3CN
toluene
THF
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
91.0/99
87.2/99
87.1/99
74.4/98
71.8/92
83.6/99
92.4/99
95.7/99
94.1/99
92.9/99
86/>90
91/>90
88/>90
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
20
20
20
20
20
20
0
-25
-78
0
1
1
24
7
1
2
CH Cl2
2
94.5/99
94.2/99
94.3/78
94.5/99
93.8/99
96.8/99
98.7/99
98.6/92
97.0/89
99.1/99
(CH Cl)2
2
THF
DMF
d
6
CH CN
3
7
8
9
toluene
toluene
toluene
toluene
toluene
4
12
48
4
10
11
12
13
e
e
e
10
25
-25
3
72
a
3
Molecular ratio: [Pd(η -C3H5)Cl]2/ligand/substrate/benzylamine )
1
/2.2/100/300. Reactions were conducted under nitrogen. The catalysts were
a
3
3
Molecular ratio: [Pd(η -C3H5)Cl]2/NaOAc/ligand/substrate/BSA/
prepared by treating [Pd(η -C H )Cl] with ligands in suitable solvent at
3
5
2
H2C(CO2Me)2 ) 2.5/4/6.0/200/600/600. Reactions were conducted under
20 °C for 1 h before use. b Determined by the HPLC, using chiral OJ-H
3
column. c The absolute configurations were assigned as R through com-
nitrogen. The catalysts were prepared by treating [Pd(η -C3H5)Cl]2 with
b
9
ligands in suitable solvent at 20 °C for 1 h before use. Determined by the
parison of the sign of specific rotations with the literature data.
c
HPLC, using chiral OD-H column. The absolute configurations were
assigned as S through comparison of the sign of specific rotations with the
8
d
e
literature data.
No NaOAc was used. See ref 4e.
TABLE 3. Allylic Substitution of 1,3-Diphenyl-2-propenyl Acetate
with Benzylaminea
However, 72 h was required for the completion of the reaction
when ferrocene ligand 1a was used at -25 °C (Table 1, entry
1
3). On the other hand, it was observed that the enantioselec-
tivity varied with the metals between the two Cp rings. When
ferrocene ligand 1a was used as ligand under -25 °C, 88% ee
was obtained and the enantioselectivity was raised to 95.7% ee
if ruthenocene 4a was used in the same conditions (Table 1,
entries 8 and 13). It was shown that the group R in the ester
group also had an effect on the asymmetric catalysis of both 4
ee (%)b,c
yield (%)
/
entry
ligand
T/°C
t
solvent
1
2
3
4
5
6
7
8
9
4a
4b
4a
4a
4a
4a
4a
4a
4a
4a
4a
4b
5
0
0
20
20
20
20
20
20
0
-25
-78
-25
20
48 h
48 h
toluene
toluene
CH2Cl2
93.8/73
89.0/68
94.2/99
91.4/99
95.0/89
93.5/99
91.9/99
94.9/76
97.6/99
99.2/99
97.0/84
99.0/99
87.2/99
20 min
20 min
7 h
20 min
20 min
20 h
40 min
1.5 h
10 h
(CH Cl)2
2
(Table 1, entries 8 and 10) and 1 (Table 1, entries 11 and 12)
THF
DMF
but with an opposite trend.
CH3CN
toluene
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Catalytic Test of Palladium-Catalyzed Asymmetric Allylic
Amination with 1. The applications of this kind of ligands were
extended to the asymmetric allylic amination of 9 with benzy-
lamine. For comparison, 1 was used first and showed excellent
asymmetric induction in this model reaction with high yields
1
1
1
1
0
1
2
3
3 h
1.5 h
(Table 2).
a
3
Molecular ratio: [Pd(η -C3H5)Cl]2/ligand/substrate/benzylamine )
/2.2/100/300. Reactions were conducted under nitrogen. The catalysts were
prepared by treating [Pd(η -C H )Cl] with ligands in suitable solvent at
The solvents showed some effect on this reaction (Table 2,
1
3
entries 1-6). Toluene was selected as the optimal one to
examine the effect of temperature on this asymmetric reaction.
It could be concluded that the temperature (Table 2, entries 6-9)
and the R in the ester group (Table 2, entries 7 and 10) had a
little effect on the enantioselectivity. Up to 99.1% ee was
obtained with 1b at 0 °C in toluene.
Catalytic Test of Palladium-Catalyzed Asymmetric Allylic
Amination with 4. First, 4 was used in the asymmetric allylic
amination with the optimal conditions mentioned above (Table
3 5 2
b
20 °C for 1 h before use. Determined by the HPLC, using chiral OJ-H
column. c The absolute configurations were assigned as R through com-
9
parison of the sign of specific rotations with the literature data.
2
, entry 7), but the results were unpleasing (Table 3, entries 1
and 2). Thus, the influence of reaction conditions of 4a upon
the asymmetric catalytic reaction was investigated. Dichlo-
romethane was found to be the optimal solvent for this reaction
according to the chemical yield and the enantioselectivity (Table
6994 J. Org. Chem., Vol. 72, No. 18, 2007

2
NoVel C -Symmetric Planar Chiral Diphosphine Ligands
TABLE 4. Allylic Substitution of Cyclohexen-1-yl Acetate with
a
b
Dimethyl Malonate and Benzylamine
FIGURE 2. The structure of palladium complex 7 and 8.
ee (%)c,d
/
entry ligand
HNu
T/˚C
t/h
solvent
yield (%)
From Table 4, it was shown that the metal ion and/or R in
the ester group had an effect on enantioselectivity in both
asymmetric alkylation and amination reaction. In contrast with
the asymmetric catalytic behavior mentioned above, ligand 4
with the larger R in the ester group resulted in higher
enantioselectivity (Table 4, entries 1-4), and the opposite trend
had also been observed with ligand 1 (Table 4, entries 5-8).
The results combined with those obtained above indicated
that the asymmetric catalytic behavior of 4 and 1 could be
correlated to their structures, which encouraged us to further
investigate their structure-property relationship in asymmetric
catalysis.
1
2
3
4
5
6
7
8
4a
4b
4a
4b
1a
1b
1a
1b
H2C(CO2CH3)2
H2C(CO2CH3)2
BnNH2
-25 0.5
-25 0.5
-25 1.5
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
toluene
toluene
78.4/93
79.8/94
60.5/86
66.7/89
81/>90
77/>90
77.4/88
69.3/92
BnNH2
-25
2
e
e
H2C(CO2CH3)2
H2C(CO2CH3)2
BnNH2
0
0
0
0
0.5
0.5
2
BnNH2
2
a
3
Molecular ratio: [Pd(η -C3H5)Cl]2/NaOAc/ligand/substrate/BSA/
b
3
H2C(CO2Me)2 ) 2.5/4/6.0/200/600/ 600. Molecular ratio: [Pd(η -C3H5)Cl]2/
ligand/substrate/benzylamine )1/2.2/100/300. Reactions were conducted
3
under nitrogen. The catalysts were prepared by treating [Pd(η -C3H5)Cl]2
with ligands in suitable solvent at 20 °C for 1 h before use. Determined
by the HPLC, using chiral AD-H column. The absolute configurations
were assigned as R through comparison of the sign of specific rotations
c
d
X-ray Structures. To clarify the different effect on enanti-
oselectivity with metal ions and R in the ester group mentioned
above, a study of the crystal structures of 7 and 8 with
palladium(II) was carried out. First, treating 4a with 1 equiv of
dichlorobis(acetonitrile)palladium(II) in benzene gave complex
1
1 e
with the literature data.
See ref 4e.
3
, entries 3-8). The temperature also affected the enantiose-
lectivity and more than 99% ee was obtained with 4a at
25 °C in this procedure (Table 3, entries 9-11). The R in
1
7a as one set of peaks in the H NMR spectrum with quantitive
-
yield (Figure 2). The corresponding complexes 7b, 8a, and 8b
were also prepared by using the same method (Figure 2). Then
a single crystal of 7a was obtained via crystallization from
dichloromethane-petroleum ether. Others were also obtained
from the component solvent in the same manner. Finally, the
X-ray structures of 7 and 8 were determined (Figure 3). Similar
to the configuration of complex 8a, which was assigned by NOE
the ester group showed little effect on the enantioselectivity
but had some effect on catalytic activity (Table 3, entries 10
and 12). The starting ligand 5 was also used in this amina-
tion, and both the catalytic activity and enantioselectivity
were inferior to that resulting with 4a (Table 3, entries 3 and
1
3).
4
e
From the asymmetric allylic substitutions mentioned above,
determination before and proved by us here, complexes 7a,
7b, and 8b also existed as configuration 2 and another possible
configuration 3 was not found (Figure 1).
ruthenocene ligands 4 showed much higher catalytic activity
and higher enantioselectivity especially in asymmetric allylic
alkylation than the corresponding ferrocene ligands 1. It was
also observed that R in the ester group had an effect on the
asymmetric allylic substitutions, particularly on the asymmetric
allylic alkylation. For ferrocene ligands 1, 1b with a larger group
gave higher enantioselectivity than did 1a. An opposite trend
had been observed in the case of 4.
As expected, the twist angles of 7a and 8a are markedly
different (23.63° in 7a and 8.15° in 8a, respectively, Figure 3)
since the different distances between the two Cp rings (3.32 Å
versus 3.68 Å) are as shown in Figure 1. In contrast to our
presumption, 7a has a larger twist angle than 8a does, which
was correlated to the leaning of the two Cp rings in 8a (see the
X-ray crystal structures in the Supporting Information). Next,
we studied the effect of R group on the twist angle. The X-ray
analysis of the single crystal of 8b showed that two kinds of
structures (A and B) existed in one crystal of 8b with different
twist angles (10.28° and 16.20°, Figure 3). Both twist angles
are larger than that of 8a. This is also possibly due to the angle
between the two Cp rings in 8a and 8b (see the X-ray crystal
structures in the Supporting Information). Different from the
results of 8a and 8b, 7b with a larger R in the ester group had
a smaller twist angle (16.05°) than did 7a.
From the results of the X-ray analysis and the palladium-
catalyzed asymmetric allylic substitutions mentioned above, we
found that the twist angle of the two Cp rings in the complexes
clearly had an effect on enantioselectivity. For the palladium-
catalyzed asymmetric allylic substitutions of 9, the ligand with
larger twist angle showed higher enantioselectivity, while an
opposite trend had been observed for the asymmetric allylic
substitution of 12.
Catalytic Test of Palladium-Catalyzed Asymmetric Allylic
Substitution with Use of 12. Allylic acetate 12 is also a classical
substrate in allylic substitution and has been extensively studied
in the Pd-catalyzed system.7
i-n,10
Compared with allylic acetate
9
, fewer good results were attained for the palladium-catalyzed
substitutions of allylic acetate 12. Therefore, we also applied
ligands 1 and 4 in the palladium-catalyzed substitutions of 12.
The reaction proceeded smoothly to give the corresponding
cyclic allylation products 13 in good yields (88-94%) and
enantioselectivities (60.5-81% ee) by using 2.5 mol % of the
catalyst (Table 4).
(
10) See reviews: (a) Trost, B. M.; Crawley, M. Chem. ReV. 2003, 103,
2
921-2294. Selected papers: (b) Molander, G. A.; Burke, J. P.; Carroll,
P. J. J. Org. Chem. 2004, 69, 8062-8069. (c) Ogasawara, M.; Ngo, H.;
Sakamoto, T.; Takahashi, T.; Lin, W. Org. Lett. 2005, 7, 2281-2284. (d)
Geisler, F.-M.; Helmchen, G. J. Org. Chem. 2006, 71, 2486-2492.
(
11) Zhao, D. B.; Sun, J.; Ding, K. L. Chem. Eur. J. 2004, 10, 5952-
5
963.
J. Org. Chem, Vol. 72, No. 18, 2007 6995

Liu et al.
FIGURE 3. Comparison of the molecular structures of 7 and 8.
+
Conclusion
H
3
PO
calcd for C50
-)-(S)-(S)-1,1′-Bis(diphenylphosphino)-2,2′-bis(methoxycar-
4
) δ -16.15; MS (MALDI) m/z 943 [M + 1 ] (100); HRMS
55 2 6 2
H N O P
Ru 943.2573, found 943.2592.
In summary, we have prepared the novel C2-symmetric planar
chiral diphosphine ligands 4 and applied them in the palladium-
catalyzed asymmetric allylic substitutions. Good to excellent
enantioselectivities, especially much higher catalytic activities,
were observed in asymmetric allylic alkylation and amination.
Compared to the corresponding ferrocene ligands 1, a different
effect of R in the ester group on enantioselectivity was observed.
For ruthenocene ligands 4, the one with a smaller R in the ester
group had higher enantioselectivity for the palladium-catalyzed
asymmetric allylic substitutions of 9. An opposite trend was
observed with 1. However, for the palladium-catalyzed asym-
metric allylic substitution of 12, ligand 4 with a larger group
resulted in somewhat higher enantioselectivity instead. The
X-ray study on the Pd(II) complex of 4 and 1 had been carried
out. The results that ligand 4 and its analogue 1 showed an
opposite trend on enantioselectivities varying with R in the ester
group might possibly account for their opposite trend of the
corresponding twist angle. It could be deduced that the twist
angle in the metallocene diphosphine ligands with only planar
chirality had a pivotal influence on the asymmetric allylic
substitutions.
(
bonyl)ruthenocene (4a). To a solution of ester amide 6 (0.53 g,
0.56 mmol) in THF (10 mL) was added a sodium methoxide
solution prepared by the addition of sodium metal (0.52 g, 22 mmol)
to methanol (35 mL). After being stirred for 24 h, the mixture was
neutralized with methanolic acetic acid, and the solvent was
removed by evaporation. The residue was dissolved in dichlo-
romethane (60 mL), and the solution was washed with water and
2 4
then brine and dried over Na SO . After removal of the solvent,
the residue was purified by silica gel column chromatography with
petroleum ether-ethyl acetate (4:1) as an eluent to afford 4a as a
D
light green solid (0.30 g, 75%). Mp 242-244 °C. [R] 27 -513.9
1
(c 0.61, CHCl ); H NMR (CDCl , 400 Hz) δ 3.70 (s, 6H), 3.87
3
3
(br s, 2H), 4.68 (br s, 2H), 5.43 (br s, 2H), 7.21-7.30 (m, 20H);
13
C NMR (CDCl
3
, 100 Hz) δ 51.8, 79.3, 79.3, 79.4, 82.5, 82.7,
8
1
5.4, 85.6, 128.1, 128.2, 128.4, 128.5, 128.53, 129.1, 132.4, 132.6,
31
34,5, 134,8, 137.7, 137.8, 139.0, 139.1, 168.80, 168.82; P NMR
, 162 Hz, 85% H PO ) δ -17.18; MS (MALDI): m/z 717
M + 1 ] (100); HRMS calcd for C38 Ru 717.0892, found
17.0922.
-)-(S)-(S)-1,1′-Bis(diphenylphosphino)-2,2′-bis(ethoxycarbo-
nyl)ruthenocene (4b). Following a procedure identical with that
described for the preparation of 4a, the reaction of 6 (0.34 g, 0.36
mmol) in THF (10 mL) with a sodium ethoxide solution prepared
by the addition of sodium metal (0.60 g, 25 mmol) to ethanol (20
(CDCl
3
3
4
+
[
7
33 4 2
H O P
(
Experimental Section
mL) for 48 h afforded 4b as a yellow solid (0.20 g, 74%). Mp
229-231 °C. [R]D27 -409.8 (c 0.78, CHCl
); H NMR (CDCl
1
Ester Amide (6). To a solution of compound 5 (1.65 g, 2.0
mmol) in THF (40 mL) were added water (2 mL), trifluoroacetic
acid (3.8 mL, 49 mmol), and Na SO (18.8 g), and this suspension
2 4
was stirred overnight at room temperature. After filtration and
removal of the solvent under reduced pressure, a mixture containing
unstable ester ammonium salt was obtained as a brown solid. To a
solution of this ester ammonium salt in dichloromethane (40 mL)
were added pyridine (7.2 mL, 89 mmol) and acetic anhydride (12.0
mL, 76 mmol), and the mixture was stirred at room temperature
overnight. The mixture was washed with 1 N HCl, water, and then
3
3
,
400 Hz) δ 1.12 (t, J ) 6.8 Hz, 6H), 3.83 (br s, 2H), 4.08-4.15 (m,
2H), 4.19-4.25 (m, 2H), 4.76 (br s, 2H), 5.42 (br s, 2H), 7.18-
7.30 (m, 20H); 13C NMR (CDCl
, 100 Hz) δ 14.3, 60.8, 77.0, 79.5,
3
79.6, 82.7, 82.9, 84.9, 85.1, 128.1, 128.2, 128.4, 128.5, 129.0, 132.4,
3
1
132.6, 134.5, 134.7, 137.7, 137.8, 139.0, 139.1, 168.4, 168.5;
P
NMR (CDCl , 162 Hz, 85% H PO ) δ -17.00; MS (MALDI) m/z
3
+
3
4
745 [M + 1 ] (100); HRMS calcd for C40
found 745.1180.
37 4 2
H O P Ru 745.1025,
2
[PdCl (4a)] (7a). A suspension of 4a (33.5 mg, 0.05 mmol) and
brine and dried over Na
2
SO
4
. After removal of the solvent, the
dichlorobis(acetonitrile)palladium (13.0 mg, 0.05 mmol) in dry
benzene (2 mL) was stirred under nitrogen for 1 h to produce a
precipitate. After the solvent was removed, 7a was obtained as a
yellow solid in quantitive yield. Recrystallization of 7a from
dichloromethane-petroleum ether provided yellow prismatic crys-
tals, which contain one molecule of dichloromethane per complex
residue obtained was purified by silica gel column chromatography
with ethyl acetate as an eluent to afford pure ester amide 6 as a
light green solid (1.56 g, 83% overall yield from 5). Mp 219-
D
1
2
20 °C. [R] 27 -359.3 (c 0.91, CHCl
δ 0.97 (d, J ) 6.4 Hz, 6H), 1.01 (d, J ) 6.4 Hz, 6H), 1.87 (s, 6H),
.98 (m, 2H), 3.82 (br s, 2H), 3.90 (t, J ) 8.8 Hz, 2H), 4.04 (dd,
J ) 11.6 Hz, 2.8 Hz, 2H), 4.37 (dd, J ) 10.8, 2.8 Hz), 4.84 (br s,
3 3
); H NMR (CDCl , 400 Hz)
1
1
1
as determined by H NMR and single crystal analysis. H NMR
(400 MHz, CDCl ) δ 3.41 (s, 6H), 4.76 (m, 4H), 5.21 (t, J ) 2 Hz,
2H), 5.29 (s, 1H, CH Cl ), 7.40-7.42 (m, 12H), 8.06-8.10 (m,
4H), 8.13-8.18 (m, 4H); C NMR (CDCl
76.6, 80.2, 85.76, 98.7, 98.9, 127.5, 127.6, 127.7, 128.2, 128.3,
3
2
H), 5.38 (br s, 2H), 6.50 (d, J ) 8.8 Hz 2H), 7.13-7.32 (m, 20H);
2
2
13
13
C NMR (CDCl
3
, 100 Hz) δ 19.3, 19.8, 23.4, 29.5, 53.5, 65.8,
3
, 100 Hz) δ 52.4, 75.0,
7
1
1
8.1, 80.2, 80.3, 81.3, 81.9, 82.0, 83.9, 84.1, 128.31, 128.36, 128.71,
3
1
28.78, 128.8, 129.6, 132.1, 132.3, 134.4, 134.6, 136.5, 136.6,
128.4, 130.7, 131.0, 135.1, 135.2 136.1, 136.2, 137.3, 167.9;
NMR (CDCl , 162 Hz, 85% H PO ) δ 42.02.
P
38.4, 138.5, 168.9, 169.0, 170.3; 31P NMR (CDCl
3
, 162 Hz, 85%
3
3
4
6996 J. Org. Chem., Vol. 72, No. 18, 2007

NoVel C
2
-Symmetric Planar Chiral Diphosphine Ligands
(4b)] (7b). Following a procedure identical with that
[PdCl
2
Hz, 1H), 7.17-7.32 (m, 10H); the enantiomeric excess was
determined by HPLC on a Chiralpak OD-H column.
described for the preparation of 7a, Recrystallization of 7b from
ethyl acetate-carbon tetrachloride provided yellow prismatic
General Procedure for Palladium-Catalyzed Asymmetric
1
3
crystals. H NMR (400 MHz, CDCl
3
) δ 0.97 (t, J ) 6.8 Hz, 6H),
Allylic Amination (11). A solution of [PdCl(η -C
3 5
H )]
2
(1.8 mg,
3
7
.92 (m, 4H), 4.74 (br s, 2H), 4.75 (br s, 2H), 5,19 (br s, 2H),
0.005 mmol) and the ligand (0.011 mmol) in dichloromethane (1
mL) was stirred for 1 h under nitrogen before use. Subsequently,
a solution of 9 (126 mg, 0.5 mmol) in dichloromethane (1.5 mL)
and benzylamine (131 µL, 1.5 mmol) was added. The reactions
were carried out at room temperature and monitored by TLC for
the disappearance of 9. When 9 disappeared, the reaction mixture
13
.36-7.41 (m, 12H), 8.04-8.06 (m, 4H), 8.16-8.18 (m, 4H);
, 100 Hz) δ 14.3, 61.5, 74.9, 76.3, 80.6, 85.5, 97.9,
8.2, 127.2, 127.3, 127.4, 128.1, 128.2, 128.3, 130.4, 130.8, 135.2,
35.3, 135.4, 136.41, 136.46, 136.5, 167.0; 31P NMR (CDCl
, 162
PO ) δ 40.79.
(1a)] (8a). Following a procedure identical with that
C
NMR (CDCl
9
1
Hz, 85% H
PdCl
3
3
3
4
[
2
2 4
was diluted with Et O (5 mL) and washed with saturated NH Cl
(aq) (25 mL). The aqueous phase was extracted with ethyl ether (5
mL) and the combined organic phase was washed with brine then
4a,e
described for the preparation of 7a, recrystallization of 8a from
dichloromethane-petroleum ether provided red-brown crystals.
[
PdCl
2
(1b)] (8b). Following a procedure identical with that
dried over Na
2 4
SO . After removal of the ether, the residue was
described for the preparation of 7a, recrystallization of 8b from
dichloromethane-ethyl acetate-petroleum ether provided red-
brown crystals. It was found that two kinds of structures (A and
B) existed in one crystal. However, this crystal gave only one set
purified on silica gel column chromatography with hexane-ethyl
1
3
ether (10:1) to afford pure product 11. H NMR (400 MHz, CDCl )
δ 3.75-3.81 (m, 2H), 4.41 (d, J ) 7.6 Hz, 1H), 6.32 (dd, J ) 7.6,
15.6 Hz, 1H), 6.58 (d, J ) 16 Hz, 1H), 7.21-7.44 (m, 15H) ppm;
the enantiomeric excess was determined by HPLC on a Chiralcel
OJ-H column.
1
1
of peaks in H NMR spectrum in CDCl
MHz, CDCl ) δ 0.94 (t, J ) 7.2 Hz, 6H), 3.85 (q, J ) 7.2 Hz,
H), 4.24 (br s, 2H), 4.47 (br s, 2H), 4.75 (br s, 2H), 5.29 (s, 1H,
CH Cl ), 7.34-7.40 (m, 12H), 8.06-8.14 (m, 4H), 8.20-8.32 (m,
H); 13C NMR (CDCl
, 100 Hz) δ 14.3, 61.5, 68.3, 72.3, 73.6,
3
solution. H NMR (400
3
4
General Procedure for Palladium-Catalyzed Asymmetric
2
2
Allylic Alkylation (13a). Compound 13a was prepared in 90-
1
4
8
1
3
94% yield. H NMR (300 MHz, CDCl
3
) δ 1.26-1.80 (m, 4 H),
4.4, 96.44, 96.47, 127.40, 127.45, 127.5, 128.0, 128.1, 128.2,
30.5, 130.9, 135.63, 135.67, 135.7, 136.4, 136.5, 136.6, 168.0;
1.96-2.01 (m, 2H), 2.87-2.93 (m, 1H), 3.29 (d, J ) 9.2 Hz, 1H),
3.73 (s, 3 H), 3.74 (s, 3 H), 5.52 (ddd, J ) 2.4, 4.0, 10 Hz, 1H),
5.75-5.80 (m, 1H); the enantiomeric excess was determined by
HPLC on a Chiralcel AD-H column.
31
P NMR (CDCl
General Procedure for Palladium-Catalyzed Asymmetric
Allylic Alkylation (10). A mixture of ligand (30 µmol) and [Pd-
3 3 4
, 162 Hz, 85% H PO ) δ 45.60.
General Procedure for Palladium-Catalyzed Asymmetric
3
(η -C
3 5
H
)Cl]
2
(4.60 mg, 12.5 µmol) in dry dichloromethane (1 mL)
Allylic Amination (13b). Compound 13b was prepared in 86-
1
was stirred at room temperature under nitrogen for 1 h, and the
resulting green solution was added to a mixture of 9 (0.252 g, 1.00
mmol) and potassium acetate (0.0020 g, 20 µmol) in dry dichlo-
romethane (2 mL) via a cannula, followed by the addition of
dimethyl malonate (0.396 g, 3.00 mmol) and BSA (0.613 g, 3.00
mmol). The reactions were carried out at room temperature and
monitored by TLC for the disappearance of 9. When 9 disappeared,
the solvent was evaporated and the resulting mixture was extracted
with ether (20 mL). The extract was washed twice with ice-cold
89% yield. H NMR (400 MHz, CDCl
3
) δ 1.45-2.04 (m, 6 H),
3.19-3.25 (m, 1H), 3.80-3.89 (dd, J ) 13.2, 18.8 Hz, 2H), 5.71-
5.80 (m, 2H), 7.22-7.36 (m, 5H); the enantiomeric excess was
determined by HPLC on a Chiralcel AD-H column.
Acknowledgment. This work was partly supported by the
Excellent Young Teachers Program of MOE, P.R.C., and the
National Natural Science Foundation of China (No. 20572070).
Supporting Information Available: Experimental procedures,
spectroscopic data for all new compounds, the CIF files for all
X-rays structures, and characterization data for products of asym-
metric allylic substitutions. This material is available free of charge
via the Internet at http://pubs.acs.org.
saturated NH
SO . After removal of the ether, the residue was purified on silica
gel column chromatography with hexane-ethyl acetate (8:1) to
4 2
Cl aqueous solution (25 mL) and then dried over Na -
4
1
afford pure product 10. H NMR (400 MHz, CDCl
3
1
3
) δ 3.51 (s,
H), 3.69 (s, 3H), 3.94 (d, J ) 10.8 Hz, 1H), 4.25 (dd, J ) 8.8,
0.8 Hz, 1H), 6.32 (dd, J ) 8.4, 15.6 Hz, 1H), 6.46 (d, J ) 15.6
JO0711440
J. Org. Chem, Vol. 72, No. 18, 2007 6997