Convenient synthesis of tropos phosphine-oxazoline ligands

Article abstract of DOI:10.1007/s11426-010-4172-z

Tropos phosphine-oxazoline ligands have shown interesting coordination behavior and excellent chiral inducing ability in asymmetry catalysis. Here we present a convenient and economic route for the synthesis of this type of ligands. According to this new route, the ligands with different electronic and steric properties have been prepared successfully.

Full text of DOI:10.1007/s11426-010-4172-z

SCIENCE CHINA
Chemistry
January 2011 Vol.54 No.1: 87–94
doi: 10.1007/s11426-010-4172-z
• ARTICLES •
· SPECIAL TOPIC · The Frontiers of Chemical Biology and Synthesis
Convenient synthesis of tropos phosphine-oxazoline ligands
LIU YuanYuan, YANG GuoQiang, YAO DongMei, TIAN FengTao & ZHANG WanBin*
School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
Received July 22, 2010; accepted September 24, 2010
Tropos phosphine-oxazoline ligands have shown interesting coordination behavior and excellent chiral inducing ability in
asymmetry catalysis. Here we present a convenient and economic route for the synthesis of this type of ligands. According to
this new route, the ligands with different electronic and steric properties have been prepared successfully.
tropos phosphine-oxazoline ligands, chirality-inducement, electronic property, steric property
tivity and enantioselectivity in many asymmetric reac-
1 Introduction
tions, were introduced by Pflatz, Helmchen and Williams
[25–27], structure modification of these ligands has been
continuously carried out by introducing chiral elements into
the ligand backbone [28, 29]. Several groups including us
have independently developed a novel kind of chiral
phosphine-oxazoline ligands 2 with atropos binaphthyl
backbone (Figure 1) [30–38]. These chiral P,N-ligands were
successfully applied in metal-catalyzed asymmetric reac-
tions and showed excellent enantioselectivities. Taking ac-
count of the advantages of chiral P,N-chelating binaphthyl
ligands 2 and the high utilization rate of tropos biphenyl
ligand 1, we designed a novel kind of chiral phos-
phine-oxazoline ligands 3 with a tropos biphenyl backbone
(Figure 1). Those ligands showed excellent catalytic activity
and enantioselectivity in Pd-catalyzed allylic alkylation and
Ir-catalyzed hydrogenation [39–41]. Although one synthetic
route of ligands 3 has been developed and reported in our
previous papers [39, 40], there are still some problems left
Transition metal-catalyzed enantioselective synthesis is one
of the most interesting and challenging fields in the modern
organic chemistry [1–4]. Since chiral ligand is one of the
origins of asymmetric induction, the design and synthesis of
novel chiral ligands are always the key issues in the devel-
opment of efficient asymmetric catalysis systems [5]. Among
the various chiral ligands, axially chiral biaryl ligands draw
much attention due to their excellent chirality transfer prop-
erties [6–18]. In view of atom economy, traditional axial-
fixed ligands require inconvenient enantiomer resolution or
diastereomer separation in their synthetic processes, and
generally, only one enantiomeric or diastereomeric pure
form of the ligands works effectively in asymmetric cata-
lytic reactions for industrial uses. Since Zhang and Ikeda
reported the first type of tropos ligand 1 [19–22], several
types of such ligands have been developed by Ikeda, Mi-
kami, Zhang and other chemists [23, 24]. These axial flexible
(tropos) ligands could form single enantiomeric or di-
astereomeric metal catalysts, which showed excellent
asymmetric catalytic activity for several types of reactions
[23, 24], due to chirality-inducement in complexing process.
Ever since PHOX ligands, which showed excellent reac-
*Corresponding author (email: wanbin@sjtu.edu.cn)
Figure 1 Bisoxazoline and phosphine-oxazoline ligands with biaryl backbone.
© Science China Press and Springer-Verlag Berlin Heidelberg 2011
chem.scichina.com
www.springerlink.com

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Liu YY, et al. Sci China Chem January (2011) Vol.54 No.1
to be solved. It’s not good enough to have two steps using
palladium salts as catalysts. Furthermore one of the reagents,
Ar2POH, must be prepared in several steps separately.
Herein, we report a much more convenient route for the
preparation of ligands 3. Aryl groups with different elec-
tronic and steric properties could be easily introduced to the
phosphine without metal catalysts. Meanwhile, we could
also shorten the synthetic route by preparation of the amide
compounds in one step from triflate intermediates.
ether) solution was added through drop funnel. The reaction
started right off. The rest of aryl bromide solution was then
added dropwise while stirring vigorously, with the reaction
being held below 50 °C. After completion of the addition,
the resulting dark-brown solution was stirred at reflux for
further 2 h.
To compound 9 (2.0 g, 8.5 mmol) in 10 mL THF (or di-
ethyl ether) between 25 °C and 40 °C was added dropwise
the above prepared Grignard reagent. The reaction mixture
was kept reflux overnight. The resulting dark brown solu-
tion was cooled to 0 °C with ice-water bath and quenched
with saturated NH4Cl solution. The separated organic layer
was washed with diluted HCl aq. The aq. layers were further
extracted with CH2Cl2 (10 mL × 3). The combined organic
layers were evaporated under reduced pressure.
The residue was dissolved into 25 mL CH2Cl2 and cooled
to 0 °C with ice-water bath. H2O2 (4.0 mL, 30%) was added
dropwise. After 1 to 3 h (TLC monitoring), the resulting
dark brown solution was cooled to 0 °C with ice-water bath
and quenched with saturated Na2SO3 aq., The separated
organic layer was washed with diluted HCl aq. The aq. lay-
ers were further extracted with CH2Cl2 (20 mL × 3). The
combined organic layers were dried over MgSO4 and
evaporated under reduced pressure. The oil residue was
purified by silica gel chromatography to give compound 13.
2 Experimental
2.1 General
All air- and moisture-sensitive manipulations were carried
out with standard Schlenk techniques under nitrogen. The
reaction solvents were distilled prior to use (toluene and
dichloromethane were distilled from CaH2, THF and diethyl
ether were distilled from Na). The commercially available
reagents were used without further purification. Column
chromatography was run on silica gel (100–200 mesh).
Melting points were measured on an X-4 microscopic melt-
1
ing point apparatus and are uncorrected. H, 13C, and 31P
NMR spectra were recorded on a VarianMERCURYplus-
400 spectrometer. HRMS was performed on a Waters Mi-
cromass Q-TOF Premier Mass Spectrometer at the Instru-
mental Analysis Center of Shanghai Jiao Tong University.
2′-(Diphenylphosphoryl)biphenyl-2-ol (13a)
83% Yield, white foam. 1H NMR (400 MHz,CDCl3)  8.99
(s, 1H), 7.78–7.83 (m, 2H), 7.56–7.61 (m, 2H), 7.48–7.53
(m, 2H), 7.31–7.39 (m, 4H), 7.27–7.30 (m, 1H), 7.16–7.24
(m, 3H), 6.98–7.05 (m, 2H), 6.43–6.51 (m, 2H); 31P NMR
(161 MHz, CDCl3)  33.3.
6-chloro-6H-dibenzo[c,e][1,2]oxaphosphinine (9)
A mixture of 2-phenylphenol (10.2 g, 60 mmol) and phos-
phorus trichloride (6.6 mL, 75 mmol) was heated slowly to
140 °C over a 5 h period. The removal of evolved hydrogen
chloride was facilitated by a slow sweep of nitrogen. To the
reaction mixture was added anhydrous zinc chloride (0.06 g,
0.44 mmol). The reaction mixture was heated to 210 °C
over a 3 h period. The reaction mixture was cooled and the
residue was distilled to give 12.6 g (90% yield) of a color-
less liquid which solidified on standing: bp 144–150 °C
2′-(Bis(4-methoxyphenyl)phosphoryl)biphenyl-2-ol (13b)
1
65% Yield, white solid. H NMR (400 MHz,CDCl3)  9.21
(br, 1H), 7.69 (dd, 2H, J = 11.8, 8.6 Hz), 7.56 (dd, 1H, J =
7.8, 1.4 Hz), 7.30–7.34 (m, 1H), 7.22–7.27 (m, 3H), 7.17
(ddd, 1H, J=14.2, 7.6, 1.4 Hz), 6.99–7.07 (m, 4H), 6.72 (dd,
2H, J = 9.0, 2.2 Hz), 6.55 (td, 1H, J =7.4, 1.2 Hz), 6.46 (dd,
1H, J = 7.6, 1.6 Hz), 3.86 (s, 3H), 3.76 (s, 3H); 31P NMR
(161 MHz, CDCl3)  33.9.
1
(5 mmHg); H NMR (400 MHz,CDCl3)  8.05 (d, 1H, J =
8.4 Hz), 8.02 (dd, 1H, J = 8.0, 1.6 Hz), 7.70 (m, 2H), 7.50
(tdd, 1H, J = 7.6, 1.3, 1.6 Hz), 7.43 (ddd, 1H, J = 8.0, 7.3,
1.6 Hz), 7.32 (tt, 1H, J = 7.6, 1.0 Hz), 7.27 (dt, 1H, J = 8.4,
1.0 Hz); 31P NMR (161 MHz, CDCl3)  134.3.
2′-(Bis(3,5-di-tert-butylphenyl)phosphoryl)biphenyl-2-ol (13c)
1
76% Yield, white solid. H NMR (400 MHz,CDCl3)  9.25
(s, 1H), 7.73 (dd, 2H, J = 12.6, 1.4 Hz), 7.65 (s, 1H), 7.57 (t,
1H, J = 7.6 Hz), 7.32–7.37 (m, 2H), 7.22–7.24 (m, 1H), 7.18
(dd, 3H, J = 13.2, 1.6 Hz), 6.97 (d, 2H, J = 4.0 Hz),
6.37–6.40 (m, 1H), 6.30 (d, 1H, J = 7.6 Hz), 1.32 (s, 18H),
1.19 (s, 18H); 31P NMR (161 MHz, CDCl3)  33.9.
2.2 General procedure for the synthesis of 13
A suspension of magnesium tunings (0.62 g, 25.5 mmol) in
5 mL of dry tetrahydrofuran (or diethyl ether) was placed
under nitrogen in a 50 mL three-necked flask provided with
a magnetic stirrer, condenser, thermometer and dropping
funnel with pressure compensation. And a grain of I2 was
added in turn. A solution of aryl bromide (21.3 mmol) in
5 mL of dry tetrahydrofuran (or diethyl ether) was placed in
a 10 mL dropping funnel. The system was heated to reflux
and then 2 mL of aryl bromide tetrahydrofuran (or diethyl
2′-(Bis(4-(trifluoromethyl)phenyl)phosphoryl)biphenyl-2-ol
(13d)
1
66% Yield, maize-yellow powder. H NMR (400 MHz,
CDCl3)  8.31 (s, 1H), 7.91–8.08 (m, 4H), 7.22–7.78 (m,
8H), 7.03 (td, 1H, J = 7.6, 2.0 Hz), 6.92 (d, 1H, J=8.0 Hz),

Liu YY, et al. Sci China Chem January (2011) Vol.54 No.1
89
6.43–6.40 (m, 2H); 31P NMR (161MHz, CDCl3)  30.1,
23.7. HRMS (Q-TOF Premier) calcd for C26H17F6O2P
(M+H)+: 507.0949; found: 507.0960.
5.6 mmol) followed by (S)-valinol (0.41 g, 4.0 mmol). Pal-
ladium(II) acetate (44.9 mg, 0.2 mmol) was added and the
flask immediately flushed with carbon monoxide (double
balloon). The flask was immersed in an oil bath (preheated
to 110 °C), and the reaction mixture was stirred for 18 h.
The reaction mixture was allowed to cool to rt and then di-
luted with CH2Cl2 (10 mL) and washed with water (15 mL).
The aqueous layer was extracted with CH2Cl2 (15 mL × 3).
The combined organics were washed with diluted HCl aq
and brine (20 mL), dried over MgSO4 and evaporated under
reduced pressure. The oil residue was purified by silica gel
chromatography to give compound 7.
2.3 General procedure for the synthesis of 5
To a stirred solution of compound 13 (2.0 mmol) in dry
CH2Cl2 (20 mL) was added dry pyridine (0.64 mL, 8.0
mmol) at 0 °C followed by dropwise addition of Tf2O (0.66
mL, 4.0 mmol). The mixture was allowed to warm up to rt
and kept reflux while stirring for 12 to 72 h (TLC monitoring).
The resulting dark brown solution was cooled to 0 °C with
ice-water bath and quenched with water. The separated or-
ganic layer was washed with diluted HCl aq. The aq. layers
were further extracted with CH2Cl2 (20 mL × 3). The com-
bined organic layers were dried over MgSO4 and evaporated
under reduced pressure. The oil residue was purified by
silica gel chromatography to give compound 5.
(S)-2′-(Diphenylphosphoryl)-N-(1-hydroxy-3-methylbutan-2-
yl)biphenyl-2-carboxamide (7a)
86% Yield, white foam. 1H NMR (400 MHz, CDCl3) (major/
minor =61:39 in CDCl3)  8.83 (d, 1H, J=8.4 Hz), 8.40 (dd,
1H, J = 9.2, 0.7 Hz) , 7.70–7.77 (m, 4H), 7.68 (dd, 1H, J =
7.7, 0.7 Hz), 7.17–7.62 (m, 25H), 6.62–6.68 (m, 2H), 6.14
(d, 1H, J = 7.7 Hz), 6.11 (d, 1H, J = 7.7 Hz), 3.60–3.74 (m,
3H), 3.23–3.35 (m, 2H), 2.44 (t, 1H, J = 6.6 Hz,), 1.89–2.00
(m, 1H), 1.52–1.67 (m, 1H), 1.01 (d, 3H, J = 7.0 Hz), 0.98
(d, 3H, J = 7.0 Hz), 0.75 (d, 3H, J=6.6 Hz), 0.40 (d, 3H, J=
7.0 Hz); 31P NMR (161 MHz, CDCl3)  33.4, 32.2.
2′-(Diphenylphosphoryl)biphenyl-2-yl trifluoromethanesul-
fonate (5a)
1
58% Yield, white foam. H NMR (400 MHz, CDCl3) 
7.65–7.71(m, 2H), 7.58–7.64 (m, 1H), 7.37–7.56 (m, 10H),
7.28–7.32 (m, 2H), 7.23–7.26 (m, 2H), 6.90–6.93 (m, 1H);
31P NMR (161 MHz, CDCl3)  27.2.
(S)-2′-(Diphenylphosphoryl)-N-(1-hydroxy-3,3-dimethylbutan-
2-yl)biphenyl-2-carboxamide (7b)
2′-(Bis(4-methoxyphenyl)phosphoryl)biphenyl-2-yl trifluorome-
thanesulfonate (5b)
60% Yield, viscous oil. 1H NMR (400 MHz, CDCl3) (major/
minor=58:42 in CDCl3)  8.44 (d, 1H, J=8.8 Hz), 8.13 (d, 1H,
J=9.9 Hz), 7.18–7.81 (m, 30H), 6.68 (td, 1H, J=1.1, 7.3 Hz),
6.60 (d, 1H, J = 7.7, 1.1 Hz), 6.15 (dd, 1H, J = 7.7, 0.7 Hz),
6.12 (dd, 1H, J = 7.3, 1.1 Hz), 3.72–3.90 (m, 4H), 3.50–3.57
(m, 1H), 3.28–3.35 (m, 1H), 1.03 (s, 9H), 0.61 (s, 9H).
1
43% Yield, white powder. H NMR (400 MHz, CDCl3) 
7.50–7.60 (m, 3H), 7.32–7.48 (m, 6H), 7.22–7.27 (m, 2H),
6.98 (dd, 1H, J = 7.6, 2.0 Hz), 6.92 (dd, 2H, J=8.8, 2.0 Hz),
6.80(dd, 2H, J = 8.4, 2.0 Hz), 3.84 (s, 3H), 3.80 (s, 3H); 31P
NMR (161 MHz, CDCl3)  28.2.
(S)-2′-(Diphenylphosphoryl)-N-(2-hydroxy-1-phenylethyl)
biphenyl-2-carboxamide (7c)
2′-(Bis(3,5-di-tert-butylphenyl)phosphoryl)biphenyl-2-yl tri-
fluoromethanesulfonate (5c)
79% Yield, white powder. 1H NMR (400 MHz, CDCl3) (major/
minor=61:39 in CDCl3)  8.48 (d, 1H, J=8.8 Hz), 8.18 (d, 1H,
J=9.9 Hz), 7.18–7.81 (m, 42H), 6.72 (d, 1H, J=7.3 Hz), 6.64
(d, 1H, J = 7.7 Hz), 3.72–3.90 (m, 1H), 3.47–3.57 (m, 2H),
3.32–3.41 (m, 3H); 31P NMR (161 MHz, CDCl3)  28.7, 27.2.
1
51% Yield, white powder. H NMR (400 MHz, CDCl3) 
7.50–7.60 (m, 4H), 7.33–7.46 (m, 7H), 7.15–7.24 (m, 2H),
6.90–6.94(m, 1H), 1.28 (s, 18H), 1.24 (s, 18H); 31P NMR
(161 MHz, CDCl3)  28.2.
2′-(Bis(4-(trifluoromethyl)phenyl)phosphoryl)biphenyl-2-yl
trifluoromethanesulfonate (5d)
(S)-2′-(Bis(4-methoxyphenyl)phosphoryl)-N-(2-hydroxy-1-
phenylethyl)biphenyl-2-carboxamide (7d)
87% Yield, white foam. 1H NMR (400 MHz,CDCl3) 
7.91–8.09 (m, 1H), 7.85 (dd, 1H, J=11.2, 7.6 Hz), 7.38–7.75
(m, 12H), 7.23–7.33 (m, 1H), 6.85–6.87 (m, 1H); 31P NMR
(161 MHz, CDCl3)  25.9. HRMS (Q-TOF Premier) calcd
for C27H16F9O4PS (M+H)+: 639.0441; found: 639.0455.
73% Yield, viscous oil. 1H NMR (400 MHz, CDCl3) (major/
minor =62:38 in CDCl3)  6.89–7.69 (m, 42H), 6.83 (dt, 1H,
J = 8.0, 1.2 Hz), 6.73 (dt, 1H, J = 8.0, 1.2 Hz), 6.54 (d, 1H,
J = 8.0 Hz), 6.21 (dd, 1H, J = 17.6, 7.8 Hz), 6.15 (d, 1H, J=
7.8 Hz), 4.95–5.03 (m, 1H), 3.89 (s, 3H), 3.88 (s, 3H), 3.84
(s, 3H), 3.83 (s, 3H).
2.4 General procedure for the synthesis of 7
(S)-2′-(Bis(3,5-di-tert-butylphenyl)phosphoryl)-N-(2-hydroxy-
1-phenylethyl)biphenyl-2-carboxamide (7e)
56% Yield, white foam. 1H NMR (400 MHz, CDCl3) (major/
To a stirred solution of triflate 5 (2.0 mmol) and 1,3-bis
(diphenylphosphino)propane (82.1 mg, 0.2 mmol) in DMSO
(12 mL) was added N,N-diisopropylethylamine (0.93 mL,

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Liu YY, et al. Sci China Chem January (2011) Vol.54 No.1
8.0 Hz), 4.39 (dd, 1H, J = 10.4, 8.0 Hz), 3.93 (t, 1H, J =
8.0 Hz), 3.90 (t, 1H, J = 8.0 Hz); 31P NMR (161 MHz,
CDCl3)  28.7, 28.1.
minor =55:45 in CDCl3)  8.56–9.72 (m, 1H), 6.91–7.85 (m,
34H), 6.46–6.59 (m, 2H), 5.98–6.04 (m, 1H), 4.95–5.10 (m,
1H), 3.50–3.57 (m, 2H), 3.28–3.35 (m, 3H), 1.28 (s, 18H),
1.24 (s, 18H), 1.22 (s, 18H), 1.19 (s, 18H); 31P NMR (161
MHz, CDCl3)  35.2, 33.9.
(S)-2-(2′-(Bis(4-methoxyphenyl)phosphoryl)biphenyl-2-yl)-4-
phenyl-4,5-dihydrooxazole (8d)
90% Yield, viscous oil. 1H NMR (400 MHz, CDCl3) (major/
minor = 66:34 in CDCl3)  9.80 (dd, 1H, J = 8.0, 1.6 Hz),
9.70 (dd, 1H, J = 8.0, 1.6 Hz), 6.68–7.60 (m, 38H), 6.16 (dd,
1H, J = 7.6, 1.2 Hz), 6.10 (dd, 1H, J = 7.6, 1.2 Hz),
5.21–5.28 (m, 2H), 4.84–4.90 (m, 2H), 3.88–3.97 (m, 2H),
3.88 (s, 3H), 3.87 (s, 3H), 3.85 (s, 3H), 3.84 (s, 3H); 31P
NMR (161 MHz, CDCl3)  32.19, 32.17.
(S)-2′-(Bis(4-(trifluoromethyl)phenyl)phosphoryl)-N-(2-hydr
oxy-1-phenylethyl)biphenyl-2-carboxamide (7f)
83% Yield, maize-yellow foam. 1H NMR (400 MHz, CDCl3)
(major/minor = 53:47 in CDCl3)  8.72–9.17 (m, 1H),
6.84–7.97 (m, 42H), 6.64–6.68 (m, 2H), 6.06–6.15 (m, 1H),
4.92–5.06 (m, 1H), 3.86–3.96 (m, 2H), 3.41–3.66(m, 3H);
31P NMR (161 MHz, CDCl3)  31.1, 30.0. HRMS (Q-TOF
Premier) calcd for C35H26F6NO3P (M+H)+: 654.1633; found:
654.1624.
(S)-2-(2′-(Bis(3,5-di-tert-butylphenyl)phosphoryl)biphenyl-2-
yl)-4-phenyl-4,5-dihydrooxazole (8e)
93% Yield, white foam. 1H NMR (400 MHz, CDCl3) (major/
minor = 58:42 in CDCl3)  7.75 (dd, 1H, J = 8.0, 1.6 Hz),
7.71 (dd, 1H, J = 8.0, 1.6 Hz), 7.05–7.56 (m, 36H), 5.29 (t,
1H, J = 9.2 Hz), 5.18 (t, 1H, J = 9.2 Hz), 4.65 (dd, 1H, J =
17.6, 7.8 Hz), 4.58 (dd, 1H, J = 17.6, 7.8 Hz), 4.00 (t, 1H,
J = 9.2 Hz), 3.28 (t, 1H, J = 9.2 Hz), 1.24 (s, 18H), 1.23 (s,
18H), 1.22 (s, 18H), 1.18 (s, 18H); 31P NMR (161 MHz,
CDCl3)  29.7, 28.5.
2.5 General procedure for the synthesis of 8
To a stirred solution of compound 7 (0.9 mmol), triethylamine
(0.44 mL, 3.1 mmol) in dichloromethane (6.0 mL) was
added methanesulfonyl chloride (90 L) at 0 °C. The mixture
was stirred for 30 min and then the resulting mixture was
warmed to rt. The reaction was monitored with TLC for a
full conversion. The reaction was quenched with water and
diluted with CH2Cl2 and washed with diluted HCl aq and
brine, dried over MgSO4 and evaporated under reduced
pressure. The oil residue was purified by silica gel chroma-
tography to give compound 8.
(S)-2-(2′-(Bis(4-(trifluoromethyl)phenyl)phosphoryl)biphenyl-
2-yl)-4-phenyl-4,5-dihydrooxazole (8f)
1
94% Yield, white foam. H NMR (400 MHz, CDCl3) (major/
minor=50:50 in CDCl3)  7.88 (t, 2H, J=9.6 Hz), 7.09–7.78
(m, 38H), 7.02 (d, 2H, J = 6.4 Hz), 5.22 (t, 1H, J =9.2 Hz),
5.18 (t, 1H, J = 9.2 Hz), 4.60 (t, 1H, J=9.6 Hz), 4.49 (t, 1H,
J=9.2 Hz), 3.96–4.02 (m, 2H); 31P NMR (161 MHz, CDCl3)
 26.4, 25.9. HRMS (Q-TOF Premier) calcd for C35H24F6NO2P
(M+H)+: 636.1527; found: 636.1529.
(S)-2-(2′-(Diphenylphosphoryl)biphenyl-2-yl)-4-isopropyl-4,
5-dihydrooxazole (8a)
93% Yield, viscous oil. 1H NMR (400 MHz, CDCl3) (major/
minor =52:48 in CDCl3)  7.69–7.75 (m, 2H), 7.18–7.65 (m,
29H), 7.10–7.18 (m, 5H), 4.15 (t, 1H, J = 8.5 Hz), 4.01 (dd,
1H, J = 12.8, 11.9 Hz), 3.79–3.88 (m, 3H), 3.74 (t, 1H, J =
8.4 Hz), 1.66–1.77 (m, 1H), 1.55–1.64 (m, 1H), 0.85 (d, 3H,
J=3.7 Hz), 0.84 (d, 3H, J=3.7 Hz), 0.83 (d, 3H, J=1.5 Hz),
0.81 (d, 3H, J = 1.5 Hz); 31P NMR (161 MHz, CDCl3) 
29.3, 28.6.
2.6 General procedure for the synthesis of 3
HSiCl3 (0.2 mL, 2.0 mmol) was added to a stirred solution
of 8 (0.2 mmol) and N,N-dimethylaniline (0.25 mL, 2.0 mmol)
in dried and degassed toluene (2 mL) under nitrogen atmos-
phere, and the mixture was heated under reflux overnight.
After cooling to 0 °C, the reaction was quenched with NaOH
aq (2 mL, 4 M) and diluted with EtOAc and washed with
water, diluted HCl aq and brine, dried over MgSO4 and
evaporated under reduced pressure. The oil residue was
purified by flash silica gel chromatography to give ligands 3.
(S)-4-tert-Butyl-2-(2′-(diphenylphosphoryl)biphenyl-2-yl)-
4,5-dihydrooxazole (8b)
1
97% Yield, viscous oil. H NMR (400 MHz, CDCl3) (major/
minor = 55:45 in CDCl3)  7.73 (dd, 1H, J = 11.4, 1.1 Hz),
7.71 (dd, 1H, J = 11.4, 1.5 Hz), 7.05–7.64 (m, 34H), 4.11 (t,
1H, J = 13.6 Hz), 3.96 (d, 1H, J = 9.9 Hz), 3.95 (d, 1H, J =
7.7 Hz), 3.78–3.85 (m, 3H), 0.82 (s, 9H), 0.77 (s, 9H); 31P
NMR (161 MHz, CDCl3)  28.3, 29.0.
(S)-2-(2′-(Diphenylphosphino)biphenyl-2-yl)-4-isopropyl-4,5-
dihydrooxazole (3a)
67% Yield, viscous oil. 1H NMR (400 MHz, CDCl3) (major/
minor = 52:48 in CDCl3)  7.89 (dd, 1H, J = 7.7, 1.5 Hz),
7.88 (dd, 1H, J = 7.7, 1.5 Hz), 7.07–7.38 (m, 33H), 6.89 (d,
1H, J = 7.7 Hz), 6.87 (d, 1H, J = 7.7 Hz), 4.09 (dd, 1H, J =
9.5, 8.4 Hz), 4.01 (dd, 1H, J = 8.1, 6.6 Hz), 3.80–3.90 (m,
(S)-2-(2′-(Diphenylphosphoryl)biphenyl-2-yl)-4-phenyl-4,5-
dihydrooxazole (8c)
96% Yield, white foam. 1H NMR (400 MHz, CDCl3) (major/
minor = 56:44 in CDCl3)  7.07–7.72 (m, 46H), 5.20 (t, 1H,
J = 4.0 Hz), 5.17 (t, 1H, J = 4.0 Hz), 4.54 (dd, 1H, J = 10.4,

Liu YY, et al. Sci China Chem January (2011) Vol.54 No.1
91
3H), 3.69 (t, 1H, J = 8.4 Hz), 1.62–1.71 (m, 1H), 1.52–1.61
(m, 1H), 0.84 (d, 3H, J = 7.0 Hz), 0.80 (d, 3H, J = 7.0 Hz),
0.79 (d, 3H, J = 6.6 Hz); 31P NMR (161 MHz, CDCl3) 
14.9, 15.0.
J = 9.2 Hz), 5.21 (t, 1H, J = 9.2 Hz), 4.55 (dd, 1H, J = 17.6,
7.8 Hz), 4.43 (dd, 1H, J = 17.6, 7.8 Hz), 3.96 (t, 1H, J=9.2
Hz), 3.82 (t, 1H, J = 9.2 Hz), 1.22 (s, 18H), 1.21 (s, 18H),
1.27 (s, 18H), 1.12 (s, 18H); 31P NMR (161 MHz, CDCl3) 
9.35, 9.97.
(S)-4-tert-Butyl-2-(2′-(diphenylphosphino)biphenyl-2-yl)-4,5-
dihydrooxazole (3b)
(S)-2-(2′-(Bis(4-(trifluoromethyl)phenyl)phosphino)biphenyl
-2-yl)-4-phenyl-4,5-dihydrooxazole (3f)
80% Yield, viscous oil. 1H NMR (400 MHz, CDCl3) (major/
minor = 55:45 in CDCl3)  7.89 (dd, 1H, J = 7.7, 1.5 Hz),
7.88 (dd, 1H, J = 7.7, 1.5 Hz), 7.07–7.39 (m, 32H), 6.88 (d,
1H, J=8.0 Hz), 6.83 (d, 1H, J=8.0 Hz), 3.93–4.06 (m, 32H),
3.75–3.89 (m, 3H), 0.81 (s, 9H), 0.73 (s, 9H); 31P NMR
(161 MHz, CDCl3)  14.95, 15.02.
80% Yield, viscous oil. 1H NMR (400 MHz, CDCl3) (major/
minor = 50:50 in CDCl3)  7.95 (td, 2H, J = 7.6, 1.4 Hz),
6.90–7.58 (m, 30H), 5.15–5.23 (m, 2H), 4.46–4.54 (m, 2H),
3.94 (t, 1H, J = 8.4 Hz), 3.86 (t, 1H, J = 8.4 Hz); 31P NMR
(161 MHz, CDCl3)  13.1, 13.2. HRMS (Q-TOF Premier)
calcd for C35H24F6NOP (M+H)+: 620.1578; found: 620.1576.
(S)-2-(2′-(Diphenylphosphino)biphenyl-2-yl)-4-phenyl-4,5-
dihydrooxazole (3c)
77% Yield, white foam. 1H NMR (400 MHz, CDCl3) (major/
minor = 51:49 in CDCl3)  7.91 (dd, 1H, J = 8.0, 1.6 Hz),
7.81 (dd, 1H, J = 8.0, 1.6 Hz), 6.91–7.47 (m, 38H), 6.77 (d,
2H, J = 8.0 Hz), 6.65 (t, 2H, J=8.0 Hz), 6.29 (d, 1H, J=6.8
Hz), 6.15 (d, 1H, J = 6.8 Hz), 5.28–5.37 (m, 2H), 3.80 (dd,
1H, J = 11.2, 4.8 Hz), 3.71 (dd, 1H, J = 11.2, 6.0 Hz), 3.59
(dd, 1H, J = 11.2, 4.8 Hz), 3.39 (dd, 1H, J = 11.2, 6.0 Hz);
31P NMR (161 MHz, CDCl3)  12.7, 12.8.
3 Results and discussion
The former route [40] reported is that the ligands were pre-
pared from 2,2′-dihydroxyl biphenyl as illustrated in Scheme 1.
2,2′-Dihydroxyl biphenyl was treated with trifluorome-
thanesulfonic anhydride (Tf2O) in the presence of pyridine
to give triflate 4. Then Pd-catalyzed insertion reactions of 4
with different diarylphosphine oxides were carried out to
afford compounds 5. Next, in the presence of methanol
Pd-catalyzed carboxylation reactions of 5 with CO gave
monocarboxylic acid esters 6. In the presence of a catalytic
amount of sodium hydride, the reaction of compounds 6
with amino alcohol afforded amide compounds 7. Then,
compounds 7 were treated with methanesulfonyl chloride in
the presence of triethylamine to give cyclic chiral monooxa-
zoline compounds 8. Finally, the reduction of 8 with tri-
chlorosilane afforded the chiral ligands 3.
However, the different diarylphosphine oxides have to be
prepared separately with diethyl phosphite and different
Grignard reagents. And this step is much more difficult for
aromatic groups with electron-withdrawing substituents.
The aromatic groups with electron-donating substituents
gave much lower yields than phenyl group. Usually two
steps are needed to obtain disubstituted compounds of di-
ethyl phosphate. That means it’s not convenient to change
the aryl groups of phosphine in our ligands. At the same
(S)-2-(2′-(Bis(4-methoxyphenyl)phosphino)biphenyl-2-yl)-4-
phenyl-4,5-dihydrooxazole (3d)
73% Yield, viscous oil. 1H NMR (400 MHz, CDCl3) (major/
minor = 53:47 in CDCl3)  7.07–7.81 (m, 34H), 6.78 (d, 4H,
J = 8.8 Hz), 6.65 (dd, 2H, J = 8.8, 2.4 Hz), 6.57 (dd, 2H, J=
8.8, 2.4 Hz), 5.26 (t, 1H, J=9.2 Hz), 5.21 (t, 1H, J=9.2 Hz),
4.61 (dd, 1H, J = 17.6, 7.8 Hz), 4.48 (dd, 1H, J = 17.6, 7.8
Hz), 4.01 (t, 1H, J=8.8 Hz), 3.92 (t, 1H, J=8.8 Hz), 3.80 (s,
3H), 3.78 (s, 3H), 3.75 (s, 3H), 3.73 (s, 3H); 31P NMR (161
MHz, CDCl3)  13.8, 13.9.
(S)-2-(2′-(Bis(3,5-di-tert-butylphenyl)phosphino)biphenyl-2-
yl)-4-phenyl-4,5-dihydrooxazole (3e)
71% Yield, white foam. 1H NMR (400 MHz, CDCl3) (major/
minor = 55:45 in CDCl3)  8.00 (dd, 1H, J = 8.0, 1.6 Hz),
7.91 (dd, 1H, J = 8.0, 1.6 Hz), 7.00–7.46 (m, 33H), 6.91 (d,
1H, J = 3.2 Hz), 6.72 (dd, 2H, J = 8.0, 3.2 Hz), 5.24 (t, 1H,
Scheme 1 Former synthetic route of the ligands.

92
Liu YY, et al. Sci China Chem January (2011) Vol.54 No.1
time, Pd-catalyzed insertion reactions of 4 with electron-
deficient diarylphosphine oxides failed. Such result was also
obtained in synthesis of other ligands [42]. But in many
cases, enantioselectivity of asymmetric catalysis is affected
dramatically by the substituents at the aryl groups of phos-
phine in the ligands. Herein, our new route can solve this
tough problem effectively.
were oxidized to compounds 13 to go over this step. As
expected, compounds 13 could react with trifluoromethane-
sulfonic anhydride smoothly to give compounds 5. And
aromatic groups with more electron-withdrawing substitu-
ents gave higher yields.
One-step reaction from methyl trifluoromethanesulfonate
to amide reported by Meyers and co-workers drew our at-
tention [44]. Therefore, we also use this one-step reaction
method in our new route to prepare compounds 7 from 5 in
good yields. Different R groups at oxazoline ring or Ar
groups at phosphine atom affect the equilibrium between
aS-7 and aR-7 slightly. This is the same for compounds 8
and ligands 3 (Table 1). When coordination of the ligands 3
with Pd or Ir ions, both of the two diastereomers of the li-
gands with different axial configurations afforded only the
complexes with S axial configuration, and no complexes
with R axial configuration were found [39–41].
Present route was started from 2-phenylphenol illustrated
in Scheme 2. At first, 2-phenylphenol was heated with PCl3
in the absence of solvent followed by a cyclization step in
the presence of ZnCl2 as a catalyst to afford 9 with up to
92% yield [43]. Compounds 9 exhibited good reactivity with
different kinds of Grignard reagents, bearing aromatic
groups with electron-donating substituents to electron-with-
drawing substituents. After recrystallization, compounds 10
could be obtained with appearance of beautiful crystal.
Many attempts had been made to use compounds 10 di-
rectly reacting with trifluoromethanesulfonic anhydride to
form compounds 11. Unfortunately, none of them succeeded,
though different bases (i.e. pyridine, triethylamine, sodium
hydride, and potassium carbonate), solvents (i.e. dichloro-
methane, dichloroethane), temperatures (from 0 °C to reflux)
and addictives (i.e. 4-dimethylaminopyridine) were tested.
Maybe compounds 10 would form anions 12 in the presence
of bases, whose nucleophilicity was too low to react with
trifluoromethanesulfonic anhydride. Thus, compounds 10
Table 1 The diastereoisomer ratio of 7, 8 and 3
Major:minor a)
a
b
c
d
e
f
7
8
3
61:39
52:48
52:48
58:42
55:45
55:45
61:39
56:44
51:49
62:38
66:34
53:47
55:45
58:42
55:45
53:47
50:50
50:50
a) The ratios of diastereomers were determined by 31P NMR integration.
Scheme 2 Synthesis of 3.

Liu YY, et al. Sci China Chem January (2011) Vol.54 No.1
93
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synthetic route of tropos phosphine-oxazoline ligands. And
several ligands with different electronic and steric proper-
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This work was supported by the National Natural Science Foundation of
China (20772081), Science and Technology Commission of Shanghai
Municipality (09431902500), and Nippon Chemical Industrial Co., Ltd. We
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