A novel axially chiral phosphine-oxazoline ligand with an axis-unfixed biphenyl backbone: Preparation, complexation, and application in an asymmetric catalytic reaction

Article abstract of DOI:10.1055/s-2006-933100

A novel chiral phosphine-oxazoline ligand 3 with an axis-unfixed biphenyl backbone was prepared. This ligand existed as a mixture of two diastereomers in equilibrium in solution. However, when it was coordinated with palladium(II), only one of the two kin

Full text of DOI:10.1055/s-2006-933100

LETTER
1185
A Novel Axially Chiral Phosphine-Oxazoline Ligand with an Axis-Unfixed
Biphenyl Backbone: Preparation, Complexation, and Application in an
Asymmetric Catalytic Reaction
An
A
xially Chiral Phosp
a
hine-Oxaz
n
oline Ligandbin Zhang,*a Fang Xie,a Hidefumi Yoshinaga,b Toshiyuki Kida,b Yohji Nakatsuji,b Isao Ikeda*b
a
School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. of China
b
Department of Applied Chemistry, Faculty of Engineering, Osaka University, Suita, Osaka 565-0871, Japan
Fax +86(21)54741297; E-mail: wanbin@sjtu.edu.cn; E-mail: ikedaisa@estate.ocn.ne.jp
Received 30 November 2005
unnecessary resolution process, we designed a novel
chiral phosphine-oxazoline ligand 3 with an axis-unfixed
biphenyl backbone. We report here the synthesis and
complexation of 3, and its application in the palladium-
Abstract: A novel chiral phosphine-oxazoline ligand 3 with an
axis-unfixed biphenyl backbone was prepared. This ligand existed
as a mixture of two diastereomers in equilibrium in solution. How-
ever, when it was coordinated with palladium(II), only one of the
two kinds of possible diastereomer complexes with different axial catalyzed allylic alkylation of 1,3-diphenyl-2-propenyl
chirality was formed. When this axis-unfixed chiral ligand was
acetate with dimethyl malonate.
used, up to 90% ee was attained for the palladium-catalyzed asym-
metric allylic alkylation.
O
Key words: P,N-ligands, chiral biaryl ligands, oxazoline ligands,
axial chirality, palladium-catalyzed allylic alkylation
R
R
R
Ph2P
Ph2P
N
N
N
N
R
O
O
O
1
2
3
Chiral oxazoline ligands derived from readily available
amino acids have found widespread use in metal-cata-
lyzed asymmetric reactions, and extensive efforts have
been devoted to the preparation of their efficient structural
derivatives.1 As it is well known that axially chiral biaryl
catalysts exhibit excellent chirality transfer properties in
asymmetric synthesis, a number of oxazoline containing
axially chiral biaryl ligands have been developed.2 These
enantiomerically stable biaryls require at least three
ortho-substituents to avoid the racemization due to the
rotation around the internal bond of the biaryls. Most of
these chiral axis-fixed biaryl ligands finally need process
of resolution and only one of the two diastereomers shows
excellent catalytic activities and enantioselectivities for
most cases. Different from these ligands with an axis-
fixed biaryl backbone, a novel kind of chiral oxazoline
ligands with an axis-unfixed biaryl backbone such as
ligand 1 was developed by us; it exists as a mixture of two
diastereomers in equilibrium in solution.3 When this
ligand was coordinated to Cu(I), only one of the two pos-
sible diastereomeric complexes was formed and showed
excellent enantioselectivities in metal-catalyzed asym-
metric reactions. On the other hand, we had also devel-
oped a novel chiral phosphino-oxazoline ligand 2 with an
axis-fixed binaphthyl backbone.4 These chiral P,N-
ligands were successfully employed in the palladium-cat-
alyzed allylic alkylation and showed excellent enantiose-
lectivities. Taking into account of the advantages of chiral
P,N-chelating binaphthyl ligand 2 and axis-unfixed bi-
phenyl ligand 1 (Figure 1) with high usage efficiency and
a: R = i-Pr; b: R = t-Bu
Figure 1
Compound 3 was synthesized as shown in Scheme 1. 2,2¢-
Biphenol as starting material was treated with trifluo-
romethanesulfonic anhydride (Tf2O) to give triflate 4.
Then the palladium-catalyzed insertion reaction of 4 with
diphenylphosphine oxide was carried out to afford com-
pound 5. Furthermore, in the presence of methanol, the
palladium-catalyzed insertion reaction of 5 with CO gave
monocarboxylic acid ester 6. In the presence of a catalytic
amount of sodium hydride, the reaction of 6 with amino
alcohol afforded amide compound 7. Then, 7 was treated
with methanesulfonyl chloride in the presence of tri-
ethylamine to give chiral monooxazoline compound 8.
Finally, the reduction of 8 with trichlorosilane afforded
the novel chiral ligand 3.5 Each of the derivatives 3a and
3b were obtained in 33% overall yield after six steps.
The behavior of ligand 3 in solution was then investigated.
As expected, two diastereomers were observed in solution
for each ligand by 1H NMR in CD2Cl2, existing in an equi-
librium due to the rotation around the internal bond of the
biphenyl backbone (Scheme 2). It was also found that the
bulkiness of the substituents on the oxazoline ring had
little effect on the ratio of the two diastereomers for the
two derivatives 3a and 3b as shown in Table 1. The com-
plexation behavior of ligands 3a and 3b to palladium(II)
using complex [Pd(h3-1,3-diphenylallyl)Cl]2 in solution
was then examined. As expected, both of the two ligands
gave only one of the two possible diastereomer complexes
9a,b with different axial chirality in CD2Cl2, respectively,
SYNLETT 2006, No. 8, pp 1185–1188
1
5.
0
5.
2
0
0
6
according to their H NMR and 31P NMR spectra like
1
Advanced online publication: 10.03.2006
DOI: 10.1055/s-2006-933100; Art ID: W32205ST
© Georg Thieme Verlag Stuttgart · New York
ligand 1 (Scheme 2 and Table 1).6

1186
W. Zhang et al.
LETTER
Pd(OAc)2
dppb
Tf2O
pyridine
97%
Ph2P(O)H
OH
O
OTf
OTf
HO
Ph2P
TfO
i-Pr2EtN
83%
4
5
Pd(OAc)2
dppb
CO (1 atm)
H
N
R
NaH, amino alcohol
O
COOMe
O
i-Pr2EtN, MeOH
Ph2P
Ph2P
O
a: 79%
b: 62%
HO
84%
6
7
O
O
HSiCl3
MesCl
O
Et3N
Ph2P
N
Ph2P
N
Et3N
R
a: 67%
b: 80%
R
a: 93%
b: 97%
8
3
a: R = i-Pr; b:R = t-Bu
Scheme 1
Then, the absolute configuration of the axial chirality of tive Cotton effect at 250 nm corresponding to S-configu-
complex 9 was investigated. It was reported that the abso- ration of axial chirality and vice versa.7,8 This result
lute configuration of 2,2¢-bridged biphenyl compounds encourages us to test our complex 9 which has a similar
could be determined by their CD spectrum, that is nega- 2,2¢-bridged eight-membered ring biphenyl backbone. As
a result, both 9a and 9b showed a negative Cotton effect
at 250 nm. This suggests that complex 9 has an S config-
uration in its axial chirality (Scheme 2).
O
O
Palladium-catalyzed asymmetric allylic alkylation as an
PPh2
N
Ph2P
N
important asymmetric reaction has been investigated us-
ing various chiral oxazoline ligands.9 We also carried out
this model reaction using 1,3-diphenyl-2-propenyl acetate
as a typical substrate to compare the ability of the new
chiral phosphine-oxazoline ligand 3 with that of ligand 2
bearing an axis-fixed biaryl backbone (Scheme 3). The re-
sults are summarized in Table 2. Using bis(trimethylsi-
lyl)acetamide (BSA) and a small amount of KOAc as the
base, both of 3a and 3b gave high chemical yields and
high enantiomeric excesses for the S-configured product.
Particularly, when 3b was used, the highest enantioselec-
tivity of 90% ee for S-configured product was obtained.
This result indicates that axis-unfixed ligand 3 can afford
the similar enantioselectivity and reactivity to axis-fixed
biaryl ligand 2. The fact that S-configured product was
obtained with ligand 3 also suggests that the complex 9
has an S configuration (Scheme 2) because in the case of
ligand 2, the S-axial chirality afforded S-configured
product and vice versa (Table 2).4
R
R
(aS)-3a,b
Pd(II)
(aR)-3a,b
Pd(II)
Ph
Ph
O
O
R
P
Pd
Pd
Pd
Ph2P
N
PPh2
N
N
R
9a,b
(aS)-9a,b
(aR)-9a,b
not found
Scheme 2
Table 1 Diastereomeric Ratio of Ligands and Complexes
Ligand or complex
3a (R = i-Pr)
Axial major:axial minora
52:48
54:46
100:0
100:0
OAc
3b (R = t-Bu)
9a (R = i-Pr)
MeO2C
CO2Me
Ph
ligand, [Pd(η3-C3H5)Cl]2, base
Ph
Ph
+
*
solvent, r.t.
Ph
9b (R = t-Bu)
CH2(CO2Me)2
a Determined by 1H NMR and 31P NMR in CD2Cl2 at 24 °C.
Scheme 3
Synlett 2006, No. 8, 1185–1188 © Thieme Stuttgart · New York

LETTER
An Axially Chiral Phosphine-Oxazoline Ligand
1187
Table 2 Palladium-Catalyzed Allylic Alkylation of 1,3-Diphenyl-
In conclusion, we have developed a novel chiral phos-
phine-oxazoline ligand 3 with an axis-unfixed biphenyl
backbone existing as a mixture of two diastereomers in
equilibrium in solution. It was found that when this com-
pound coordinated to palladium(II), only one of the two
possible kinds of diastereomer complexes with different
axial chirality was formed. With this compound as a chiral
ligand, up to 90% ee was attained for the palladium-cata-
lyzed asymmetric allylic alkylation.
2-propenyl Acetatea
Ligand
Solvent
Base
Yield (%) ee, %b
(config)c
3a
THF
BSA–KOAc
BSA–KOAc
BSA–KOAc
BSA–KOAc
BSA–KOAc
BSA–KOAc
96
89
97
96
93
91
83 (S)
CH2Cl2
THF
82 (S)
88 (S)
90 (S)
85 (S)
90 (R)
3b
CH2Cl2
THF
Acknowledgment
(aS)-2a4
(aR)-2a4
This work was partly supported by the Excellent Young Teachers
Program of MOE, P. R. C., the National Natural Science Foundati-
on of China (No. 20572070) and STCSM Foundation of Shanghai
(03DZ19205).
THF
a Conducted at r.t. with 1,3-diphenyl-2-propenyl acetate (1 mmol),
dimethylmalonate (3 mmol), BSA (3 mmol), and KOAc (20 mmol) in
3 mL of solvent under argon in the presence of the catalyst which
was prepared from ligand (30 mmol) and [Pd(h3-C3H5)Cl]2 (13 mmol)
in 1 mL solvent for 1 h before use. All of the reactions finished within
1 h.
References and Notes
(1) (a) Bolm, C. Angew. Chem., Int. Ed. Engl. 1991, 30, 542.
(b) Pfaltz, A. Acc. Chem. Res. 1993, 26, 339. (c) Togni, A.;
Venanzi, L. M. Angew. Chem., Int. Ed. Engl. 1994, 33, 497.
(d) Williams, J. M. J. Synlett 1996, 705. (e) Ghosh, A. K.;
Mathivanan, P.; Cappiello, J. Tetrahedron: Asymmetry
1998, 9, 1. (f) Pfaltz, A. Synlett 1999, 835. (g) Rechavi, D.;
Lemaire, M. Chem. Rev. 2002, 102, 3467. (h) Desimoni,
G.; Faita, G.; Quadrelli, P. Chem. Rev. 2003, 103, 3119.
(i) McManus, H. A.; Guiry, P. J. Chem. Rev. 2004, 104,
4151. (j) Meyers, A. I. J. Org. Chem. 2005, 70, 6137.
(2) Selected papers: (a) Uozumi, Y.; Kato, K.; Hayashi, T. J.
Am. Chem. Soc. 1997, 119, 5063. (b) Uozumi, Y.; Kato, K.;
Hayashi, T. J. Org. Chem. 1998, 63, 5071. (c) Ogasawara,
M.; Yoshida, K.; Kamei, H.; Kato, K.; Uozumi, Y.; Hayashi,
T. Tetrahedron: Asymmetry 1998, 9, 1779. (d) Uozumi, Y.;
Kyota, H.; Kato, K.; Ogasawara, M.; Hayashi, T. J. Org.
Chem. 1999, 64, 1620. (e) Imai, Y.; Zhang, W.; Kida, T.;
Nakatsuji, Y.; Ikeda, I. Synlett 1999, 1319. (f) Kodama, H.;
Ito, J.; Hori, K.; Ohta, T.; Furukawa, I. J. Organomet. Chem.
2000, 603, 6. (g) Imai, Y.; Matsuo, S.; Zhang, W.;
Nakatsuji, Y.; Ikeda, I. Synlett 2000, 239. (h) Gladiali, S.;
Loriga, G.; Medici, S.; Taras, R. J. Mol. Catal. A: Chem.
2003, 196, 27.
b Determined by HPLC (Chiralcel OD).
c Determined by comparing the sign of its optical rotation with litera-
ture data.
Finally, the stability and reactivity of reaction intermedi-
ates (S)-9 were examined. For both (S)-9a and (S)-9b, two
diastereomeric intermediates with W- and M-type were
observed in their 1H NMR and 31P NMR spectrum in the
ratio of 54:46 and 58:42, respectively (Scheme 4). The
major was assigned as W-type by NOE observation be-
tween the proton of the substituent on oxazoline and Ha,
and the minor was assigned as M-type by observing no
NOE (Scheme 4). For the asymmetric alkylation, it is
known that, because the trans effect directs nucleophilic
attack to the allylic terminus trans to phosphorus atom,10
the W-type intermediate leads to the product of R con-
figuration, and the M-type one leads to the product of S
configuration.11 In the present case, with both 9a and 9b,
the S-configured product was obtained. This result shows
that the minor M-type diastereomer has much more reac-
tivity than the major W-type one, due to the position trans
to the phosphorus atom becoming more cationic, caused
by the steric repulsion between the substituent on oxazol-
ine ring and phenyl group.
(3) (a) Imai, Y.; Zhang, W.; Kida, T.; Nakatsuji, Y.; Ikeda, I.
Tetrahedron Lett. 1997, 38, 2681. (b) Imai, Y.; Zhang, W.;
Kida, T.; Nakatsuji, Y.; Ikeda, I. J. Org. Chem. 2000, 65,
3326.
(4) Imai, Y.; Zhang, W.; Kida, T.; Nakatsuji, Y.; Ikeda, I.
Tetrahedron Lett. 1998, 39, 4343.
(5) Compound 3a: 1H NMR (400 MHz, CDCl3; major/
minor = 57:43 in CDCl3): d = 7.89 (dd, J = 1.5, 7.7 Hz, 1 H),
7.88 (dd, J = 1.5, 7.7 Hz, 1 H), 7.38–7.07 (m, 32 H), 6.89 (br
d, J = 7.7 Hz, 1 H), 4.09 (dd, J = 8.4, 9.5 Hz, 1 H), 4.01 (dd,
J = 6.6, 8.1 Hz, 1 H), 3.90–3.80 (m, 3 H), 3.69 (t, J = 8.4 Hz,
1 H), 1.71–1.62 (m, 1 H), 1.61–1.52 (m, 1 H), 0.84 (d,
J = 7.0 Hz, 3 H), 0.80 (d, J = 7.0 Hz, 3 H), 0.84 (d, J = 6.9
Hz, 3 H). 31P NMR (CDCl3, PPh3 = –6.0 ppm): d = –14.8
(major), –15.0 (minor). HRMS (EI): m/z calcd for
O
O
N
Ph2P
Ph
Ph2P
Ph
N
Ha
Pd
Pd
R
Ph
R
Ph
Ha
9a,b
a: R = i-Pr; b: R = t-Bu
M-type
minor
W-type
major
C30H28NOP: 449.1910; found: 449.1905. Anal. Calcd for
C31H30NOP: C, 80.16; H, 6.28; N, 3.12. Found: C, 79.78; H,
5.89; N, 3.11. [a]D25 = –54.2 (c 0.48, CHCl3).
9a: 0.4%
9b: 2.8%
no NOE
NOE:
Compound 3b: 1H NMR (400 MHz, CDCl3, major/
minor = 53:47 in CDCl3): d = 7.89 (dd, J = 1.1, 7.7 Hz, 1 H),
7.88 (dd, J = 1.1, 7.7 Hz, 1 H), 7.39–7.07 (m, 32 H), 6.88 (br
d, J = 8.1 Hz, 1 H), 6.83 (br d, J = 8.1 Hz, 1 H), 4.06–3.93
(m, 3 H), 3.89–3.75 (m, 3 H), 0.81 (s, 9 H), 0.73 (s, 9 H).
Scheme 4
Synlett 2006, No. 8, 1185–1188 © Thieme Stuttgart · New York

1188
W. Zhang et al.
LETTER
(7) (a) Suzuki, H. Bull. Chem. Soc. Jpn. 1959, 32, 1340.
31P NMR (CDCl3, PPh3 = –6.0 ppm): d = –14.9 (major),
–15.0 (minor). HRMS (EI): m/z calcd for C31H30NOP:
463.2067; found: 463.2064. Anal. Calcd for C31H30NOP: C,
80.32; H, 6.52; N, 3.02. Found: C, 80.03; H, 6.62; N, 2.87.
[a]D25 –28.7 (c 0.52, CHCl3).
(b) Suzuki, H. Electronic Absorption Spectra and Geometry
of Organic Molecules; Academic Press: New York, 1967,
262.
(8) (a) Superchi, S.; Casarini, K.; Laurita, A.; Bavoso, A.;
Rosini, C. Angew. Chem. Int. Ed. 2001, 40, 451.
(b) Isaksson, R.; Rashidi-Ranjbar, P.; Sandstrom, J. J. Chem.
Soc., Perkin Trans. 1 1991, 1147.
(6) Complex 9 is formed with only one kind of axial chirality,
but exists as a mixture of two diastereomers with W- and
M-type.
Compound 9a: 1H NMR (400 MHz, CD2Cl2, major/
minor = 54:46 in CD2Cl2): d = 7.86–6.53 (m, 56 H), 5.91 (br
d, J = 8.0 Hz, 1 H), 5.88 (br d, J = 7.6 Hz, 1 H), 5.80–5.68
(m, 2 H), 4.94 (d, J = 10.9 Hz, 1 H), 4.85 (d, J = 12.3 Hz, 1
H), 3.97–3.80 (m, 4 H), 3.34 (t, J = 9.4 Hz, 1 H), 2.48–2.38
(m, 1 H), 1.86–1.77 (m, 1 H), 1.50–1.40 (m, 1 H), 0.71 (d,
J = 6.9 Hz, 3 H), 0.51 (d, J = 6.9 Hz, 3 H), 0.38 (d, J = 6.9
Hz, 3 H), 0.08 (d, J = 6.9 Hz, 3 H). 31P NMR (CD2Cl2,
PPh3 = –6.0 ppm): d = 28.8 (minor), 24.8 (major).
Compound 9b: 1H NMR (400 MHz, CD2Cl2, major/
minor = 58:42 in CD2Cl2): d = 7.87–6.58 (m, 55 H), 6.54
(dd, J = 11.2, 13.1 Hz, 1 H), 5.93–5.83 (m, 3 H), 5.53 (t,
J = 10.9 Hz, 1 H), 4.94 (d, J = 11.2 Hz, 1 H), 4.80 (d,
J = 12.3 Hz, 1 H), 4.03–3.96 (m, 2 H), 3.87 (dd, J = 9.1, 10.5
Hz, 1 H), 3.68 (dd, J = 5.4, 10.5 Hz, 1 H), 3.09 (t, J = 9.4 Hz,
1 H), 2.23 (br s, 1 H), 0.64 (s, 9 H), 0.43 (s, 9 H). 31P NMR
(CD2Cl2, PPh3 = –6.0 ppm): d = 29.1 (minor), 25.2 (major).
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Synlett 2006, No. 8, 1185–1188 © Thieme Stuttgart · New York