Efficient oxidative resolution of a P-stereogenic triarylphosphine and asymmetric synthesis of a P-stereogenic atropoisomeric biphenyl diphosphine dioxide

Article abstract of DOI:10.1016/j.tetasy.2010.06.014

Racemic 3-methoxyphenyl(1-naphthyl)phenylphosphine 1 was effectively resolved via an oxidative resolution procedure utilizing l-menthyl bromoacetate as the resolving agent to give enantiopure 3-methoxyphenyl(1-naphthyl) phenylphosphine oxide (R)-2 in 41% yield. Reduction of the resolved (R)-4 with HSiCl₃/NEt₃ provided the corresponding phosphine (R)-1 in >97% ee. Ortho-iodination of the enantiopure (R)-4 followed by Ullmann coupling of the resulting iodoarylphosphine oxide gave a P-stereogenic and atropoisomeric biphenyl diphosphine dioxide as a single diastereoisomer. The latter transformation constitutes the first example of an effective transfer of a P-centered chirality to an axial chirality of the atropoisomeric biaryl system. The absolute configurations of the resolved phosphine and the atropoisomeric biaryl system have also been established.

Full text of DOI:10.1016/j.tetasy.2010.06.014

Tetrahedron: Asymmetry 21 (2010) 1401–1405
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Efficient oxidative resolution of a P-stereogenic triarylphosphine
and asymmetric synthesis of a P-stereogenic atropoisomeric biphenyl
diphosphine dioxide
*
Kamil Dziuba, Anna Flis, Anna Szmigielska, K. Michał Pietrusiewicz
Department of Organic Chemistry, Maria Curie-Skłodowska University, Gliniana 33, 20-614 Lublin, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
Racemic 3-methoxyphenyl(1-naphthyl)phenylphosphine 1 was effectively resolved via an oxidative res-
olution procedure utilizing L-menthyl bromoacetate as the resolving agent to give enantiopure 3-
Received 1 March 2010
Accepted 10 June 2010
Available online 2 July 2010
methoxyphenyl(1-naphthyl)phenylphosphine oxide (R)-2 in 41% yield. Reduction of the resolved (R)-4
with HSiCl3/NEt3 provided the corresponding phosphine (R)-1 in >97% ee. Ortho-iodination of the
enantiopure (R)-4 followed by Ullmann coupling of the resulting iodoarylphosphine oxide gave a P-ste-
reogenic and atropoisomeric biphenyl diphosphine dioxide as a single diastereoisomer. The latter trans-
formation constitutes the first example of an effective transfer of a P-centered chirality to an axial
chirality of the atropoisomeric biaryl system. The absolute configurations of the resolved phosphine
and the atropoisomeric biaryl system have also been established.
Dedicated to Professor Henri Kagan on the
occasion of his 80th birthday
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
as a chiral substrate for the asymmetric synthesis of an atropoiso-
meric biphenyl diphosphine dioxide providing the first case of a
Over the past three decades, great progress has been made in
the field of asymmetric catalysis by using homogeneous catalysts
based on transition metal complexes modified by chiral phosphine
ligands.1 These chiral ligands generally fall into three main catego-
ries: ligands possessing stereogenic phosphorus centers;2 ligands
containing stereogenic carbon centers;3 and ligands with axial4
or planar5 chirality. A number of hybrid ligands possessing both
stereogenic phosphorus and stereogenic carbon centers have been
synthesized,6 but those which bear both axial chirality and a stere-
ogenic phosphorus are still very rare.7
Most of the chiral phosphine ligands utilized in asymmetric
catalysis have been bidentate ligands. In recent years, however, a
growing interest in the use of chiral monophosphine ligands has
also been observed.8 However, phosphines with stereogenic phos-
phorus centers are relatively difficult to obtain in a nonracemic
form.9 This remains especially true for P-stereogenic triarylphos-
phines which despite their closest structural analogy to the parent
icon ligand, triphenylphosphine, have not been yet made accessi-
ble in a practical way.10
highly efficient transfer of P-centered chirality to an axial chirality
of the atropoisomeric biphenyl system will also be described.
2. Results and discussion
Racemic 1 was conveniently synthesized by the sequential treat-
ment of dichlorophenylphosphine with 1-naphthylmagnesium
bromide at ꢀ5 °C followed by m-anisylmagnesium bromide at ꢀ5
to 36 °C under an inert atmosphere. Crystallization of the crude, oily
product from ethanol afforded crystalline phosphine 1 in 61% yield.
For the resolution of rac-1 we decided to use our oxidative resolu-
tion protocol which we previously applied successfully for the res-
olutions of monocyclic and bicyclic phospholenes.11 The resolution
protocol developed for rac-1 is delineated in Scheme 1.
Racemic phosphine 1 was reacted with L-menthyl bromoacetate
to give an equimolar mixture of the two P-epimeric phosphonium
bromides 2 (96%) in the form of an oil. Attempts to crystallize these
oily bromides from a variety of solvents were unsuccessful.
The replacement of the bromide anion in 2 with hexafluoro-
phosphate anion by metathesis with ammonium hexafluorophos-
phate followed by washing off ammonium bromide resulted in
the formation of oily phosphonium hexafluorophosphate salts 3.
This time, however, upon dissolution in warm ethanol the oily
phosphonium salts 3 yielded white crystals which consisted
mainly of one P-epimeric salt 3. A single recrystallization of the
crystals from the same solvent furnished pure P-epimer of 3 of
practically 100% diastereomeric purity (NMR) and in a remarkable
Herein, we report an efficient gram-scale oxidative resolution
of a model triarylphosphine, that is, 3-methoxyphenyl(1-naph-
thyl)phenylphosphine 1. The use of the derived enantiopure P-ste-
reogenic 3-methoxyphenyl(1-naphthyl)phenylphosphine oxide 4
* Corresponding author.
E-mail address: kazimierz.pietrusiewicz@poczta.umcs.lublin.pl (K.M. Pietrusie-
wicz).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.06.014

1402
K. Dziuba et al. / Tetrahedron: Asymmetry 21 (2010) 1401–1405
H3CO
CO2(L-Menthyl)
..
-
H3CO
Br
P
BrCH2CO2(L-Menthyl)
96%
1. NH4PF6
P+
2. two crystallizations
41%
1
2
OCH3
CO2(L-Menthyl)
-
PF6
O
P
H3CO
H3CO
..
P+
P
Cl3SiH, Et3N
1. NaH, THF
2. PhCHO
95%
benzene
95%
(SP)-3
(RP)-1
(RP)-4
[α]D = - 6.0 (c 1.3, CH2Cl2)
[α]D = + 3.2 (c 1.1, CH2Cl2)
[α]D = - 4.8 (c 1.0, CH2Cl2)
> 97% ee
> 99% ee
> 99% de
Scheme 1. Resolution of rac-1.
41% yield (82% calculated for one P-epimer). The absolute configu-
rations at P in the phosphonium salts 3 were assigned on the basis
of the single crystal X-ray diffraction study of the resolved more
crystalline P-epimer 3. The X-ray structure of the resolved crystal-
line 3 showing also its (SP)-absolute configuration is presented in
Figure 1.
by oxidation with H2O2, known to occur with complete retention
of configuration at P.14 The correlation is shown in Scheme 2 and
supports the expected assignment of the RP configuration to the re-
solved phosphine 1.
OCH3
O
P
H2O2, CH2Cl2
(RP)-1
99%
(SP)-4
[α]D = + 3.1 (c 1.0, CH2Cl2)
> 97% ee
Scheme 2. Correlation of the absolute configuration of (RP)-(ꢀ)-1 with (SP)-(ꢀ)-4.
P1
O2
The successful preparation of the enantiopure P-stereogenic tri-
arylphosphine oxide containing an m-anisyl substituent at P opened
the way to the synthesis of the atropoisomeric biaryl diphosphine
dioxide system that bears both axial chirality and stereogenic phos-
phorus centers. Following the procedure described by Schmid
et al.4e for the synthesis of the MeO-BIPHEP ligand, (RP)-4 was
ortho-metallated by treatment with LDA at a low temperature and
then reacted with iodine to furnish aryl iodide (SP)-5 in 74% yield
(Scheme 3). Coupling of (SP)-5 under Ullmann conditions15 gave
the expected biphenyl diphosphine dioxide 6 in only 27% yield,
but in the form of a single diastereoisomer.16 The rest of the isolated
material was identified as (RP)-4, which apparently resulted from
deiodination of the substrate under the reaction conditions. The ob-
served difficulty of coupling of (SP)-6 could be associated with con-
siderable steric crowding of the system bearing very large tertiary
1-naphthylphosphine oxide groups at the ortho-positions.
O3
F2
F1
O1
F3
F4
P2
F6
F5
Figure 1. ORTEP drawing of (SP)-3 drawn with 30% probability ellipsoids, except for
the hydrogen atoms which are represented as spheres of arbitrary size.
The absolute configuration of the coupled product was assigned
by the single crystal X-ray diffraction study, which revealed the
(Sa)-absolute chirality of its biphenyl axis (Fig. 2). It is worth stress-
ing that the observed asymmetric coupling of (RP)-5 to (Sa,SP,SP)-6
with virtually 100% asymmetric induction is remarkable as it con-
stitutes the first case of an efficient transfer of the P-centered chi-
rality to the axial chirality of the atropoisomeric biaryl system.
Removal of the auxiliary L-menthyl acetate moiety from the re-
solved (SP)-3 was accomplished by means of the stereochemically
well-behaved Wittig reaction by the treatment of (SP)-3 with
NaH and benzaldehyde, which afforded virtually enantiopure
(RP)-412 in 95% yield and with the retention of configuration at P.13
Reduction of (RP)-4 by Cl3SiH/Et3N proceeded with high stere-
oselectivity and with inversion of configuration at P and eventually
gave the resolved phosphine (RP)-1 in 95% yield and in >97% ee. The
enantiomeric excess of (RP)-1 as well as its absolute configuration
was established through the correlation with the enantiopure
oxide 4 in which the phosphine was converted in a single step
3. Conclusion
In conclusion, we have developed a practical procedure for the
resolution of a P-stereogenic 3-methoxy(1-naphthyl)phenylphos-

K. Dziuba et al. / Tetrahedron: Asymmetry 21 (2010) 1401–1405
1403
under argon before use. Nuclear magnetic resonance (NMR) spectra
were recorded on a Bruker AV400 (1H 300 MHz, 31P 121.5 MHz, 13
I
O
P
H3CO
C
75 MHz) spectrometer. All spectra were obtained in deuterochloro-
form solutions, unless mentioned otherwise, and the chemical shifts
d are expressed in ppm using internal reference to TMS and external
reference to 85% H3PO4 in D2O for 31P. Coupling constants (J) are gi-
ven in Hertz. The abbreviations of signal patterns are as follows: s—
singlet, d—doublet, t—triplet, q—quartet, m—multiplet, b—broad, i—
intensive. Mass spectra (MS) were run on AMD-604 spectrometer
with a standard ionization potential 70 eV (EI MS). Infrared spectra
were recorded on a Perkin–Elmer Spectrum 2000 spectrometer. Ele-
mental analyses were measured on the Perkin–Elmer CHN 2400.
Optical rotations were measured on a Perkin–Elmer 341LC digital
polarimeter. Thin-layer chromatography (TLC) was done on silica
gel (Kieselgel 60, F254 on aluminum sheet, Merck). All column chro-
matographic separations and purifications were conducted by using
Merck Slica Gel 60 (230–400 mesh), unless noted otherwise.
LDA, THF
(RP)-4
º
I2, -78 C
74%
(SP)-5
[α]D = -14.5 (c 1.0, CH2Cl2)
O
Ph
P
Cu, DMF
H3CO
H3CO
1-Naphth
Ph
1-Naphth
º
140 C
P
27%
O
4.2. 3-Methoxyphenyl(1-naphthyl)phenylphosphine rac-1
(Sa,SP,SP)-(+)-6
[α]D = + 87.0 (c 0.5, EtOH)
At first, 3.4 g (0.14 mol) of magnesium was suspended in 100 mL
of dry diethyl ether under argon in a 2 L four-necked flask equipped
with a condenser, thermometer, mechanical stirrer, and a dropping
funnel with pressure compensation. A solution of 29 g (0.14 mol) of
1-bromonaphthalene in 150 mL of diethyl ether was added drop-
wise to the suspension within 0.5 h. After completion of the addi-
tion, the solution was stirred at 35–40 °C for the next 2 h. The
reaction mixture was cooled to room temperature and treated
dropwise under argon with a solution of 25.1 g (0.14 mol) of dichlo-
rophenylphosphine in 100 mL of diethyl ether at about ꢀ5 °C with-
in 1 h. In a separate flask a solution of 31.4 g (0.168 mol) of 3-
bromoanisole in 150 mL of diethyl ether was added dropwise to
the suspension of 4.1 g of magnesium in 100 mL of diethyl ether un-
der argon within 0.5 h. After the addition the reaction mixture was
stirred at 35–40 °C for further 2 h. The resulting Grignard solution
was cooled to room temperature and added dropwise within 1 h
at ꢀ5 °C to the solution of chloro(1-naphthyl)phenylphosphine ob-
tained above. After an additional stirring period of 1 h at about 0 °C
the reaction mixture was heated at 35–40 °C for a further 2 h. Sub-
sequently, 350 mL of 30% aq NH4Cl was added through a dropping
funnel with vigorous stirring. The aqueous phase was separated and
extracted with 200 mL of dichloromethane. The combined organic
phases were washed with 200 mL of water and dried over anhy-
drous magnesium sulfate, filtered, and evaporated to yield a yellow
oil. The oil was dissolved in 300 mL of a mixture of warm ethanol
and hexane and cooled in a refrigerator. The white crystals obtained
were filtered and washed twice with 50 mL of ethanol and dried in
vacuum, The overall yield of 3-methoxyphenyl(1-naphthyl)phenyl-
phosphine was 29.4 g (61.3%). Mp = 107–109 °C. Anal. Calcd for
Scheme 3. Synthesis of atropoisomeric biphenyl diphosphine dioxide (Sa,SP,SP)-6 by
means of asymmetric Ullmann coupling.
C12
C13
C11
C21
C13
C22
C23
C12
C11
C9
C20
C9
C10
C16
C8
P1
O1
C17
C8
C10
O1
C6
C20
C15
C1
C21
P1
C18
C6
C7
C5
C14
C22
C2
C16
C4
C19
C1
C3
C2
C3
O2
O2
C15
C14
C19
C23
C5
C4
C17
C7
C18
Figure 2. ORTEP drawing of (Sa,SP,SP)-6 drawn with 30% probability ellipsoids,
except for the hydrogen atoms which are represented as spheres of arbitrary size.
phine. The resolution was accomplished by fractional crystalliza-
tion of its diastereomeric L-menthoxycarbonylmethylphosphoni-
um salts. The resolved diastereomerically pure salt, (SP)-3, was
then transformed into enantiopure phosphine (RP)-1 by the Wittig
process followed by silane reduction of the intermediate enantio-
pure phosphine oxide (RP)-4. The enantiopure (RP)-4 was used as
a substrate for the highly effective asymmetric synthesis of the
atropoisomeric and P-stereogenic biphenyl diphosphine by a pro-
cedure involving ortho iodination of the anisyl ring followed by
the Ullmann coupling of the resulting aryl iodide. The first efficient
transfer of the P-centered chirality to the axial chirality of the
atropoisomeric biaryl system was thus accomplished. Efforts to
generalize the developed resolution procedure to other triaryl-
phosphines as well as to synthesize other P-stereogenic atropoiso-
meric bidentate ligands are currently in progress.
C
23H19OP (342.37): C, 80.69; H, 5.59. Found: C, 80.59; H, 5.55. 31P
NMR (121.5 MHz) d ꢀ13.10 (s). 1H NMR (300 MHz) d 3.69 (s, 3H),
6.85–8.49 (m, 16H). 13C NMR (75 MHz, CDCl3) (d) 159.7 (d, J =
7.5 Hz); 138.0 (d, J = 7.5 Hz); 136.3 (d, J = 7.5 Hz); 135.4 (d, J =
15 Hz); 134.5 (d, J = 15 Hz); 134.3 (d, J = 22.5 Hz); 133.5 (d,
J = 7.5 Hz); 132.2; 129.7 (d, J = 7.5 Hz); 129.6; 128.8 (d, J = 15 Hz);
128.7 (d, J = 7.5 Hz); 126.7; 126.5; 126.4; 126.3; 126.1; 126.1;
125.7; 125.7; 119.6 (d, J = 22.5 Hz); 114.6; 55.2.
4.3. (2-Isopropyl-5-methylcyclohexyloxycarbonylmethyl)
(methoxyphenyl) (naphthalen-1-yl)phenylphosphonium
bromide 2 and (2-isopropyl-5-methylcyclohexyloxy
carbonylmethyl) (3-methoxyphenyl) (naphthalen-1-yl)phenyl
phosphonium hexafluorophosphate (SP)-3
4. Experimental
4.1. General
The reagents were purchased from commercial suppliers and
used without further purification. Solvents were dried and distilled
A solution of 15.25 g (0.055 mol) of
50 mL of dry benzene was added dropwise to 18.5 g (0.054 mol) of
L-menthyl bromoacetate in

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K. Dziuba et al. / Tetrahedron: Asymmetry 21 (2010) 1401–1405
3-methoxyphenyl(1-naphthyl)phenylphosphine suspended in
200 mL of dry benzene under argon in a Schlenk-type flask. After
the addition, the reaction mixture was stirred at 60 °C for further
22 h. Then, 9.6 g (0.06 mol) of ammonium hexafluorophosphate
was added portionwise to the reaction mixture cooled to room
temperature. After an additional stirring period of 22 h, the reac-
tion mixture was evaporated and 150 mL of CH2Cl2 was added.
The organic phase was washed twice with 50 mL of water, sepa-
rated, dried over anhydrous magnesium sulfate, filtered, and evap-
orated. The resulting yellow oil was dissolved in 250 mL of warm
ethanol and slowly cooled to room temperature. The white crystals
obtained were filtered, washed twice with 50 mL of ethanol, and
dried in vacuum. Additional recrystallization from ethanol gave
14.1 g (41%) of diastereomerically pure (>99% de by NMR) (SP)-3.
Mp = 178–179 °C. Anal. Calcd for C35H40F6O3P2 (684.63): C, 61.40;
methane (60%) as eluent to give 0.33 g (95% yield) of (RP)-1 of >97%
enantiomeric purity (as assigned by stereoretentive reoxidation
experiment shown in Scheme 2). Mp = 112 °C. Anal. Calcd for
C
23H19OP (342.37): C, 80.69; H, 5.59. Found: C, 80.56; H, 5.45.
]
[a
D = ꢀ4.8 (c 1.0, CH2Cl2). 31P NMR (121.5 MHz) d ꢀ13.15 (s).
1H NMR (300 MHz) d 3.70 (s, 3H), 6.84–8.43 (m, 16H). 13C NMR
(75 MHz, CDCl3) (d) 159.7 (d, J = 7.5 Hz); 138.0 (d, J = 7.5 Hz);
136.3 (d, J = 7.5 Hz); 135.4 (d, J = 15 Hz); 134.5 (d, J = 15 Hz);
134.3 (d, J = 22.5 Hz); 133.5 (d, J = 7.5 Hz); 132.2; 129.7 (d, J =
7.5 Hz); 129.6; 128.8 (d, J = 15 Hz); 128.7 (d, J = 7.5 Hz); 126.7;
126.5; 126.4; 126.3; 126.1; 126.1; 125.7; 125.7; 119.6 (d, J =
22.5 Hz); 114.6; 55.2.
4.6. 3-Methoxyphenyl(1-naphthyl)phenylphosphine oxide (SP)-
4 from the correlation experiment
H, 5.89. Found: C, 61.31; H, 5.85. [
a]
D = ꢀ6.0 (c 1.3, CHCl3). 31P
NMR (121.5 MHz) d 21.29 (s), ꢀ144.0 (sept, J = 713 Hz, PF6ꢀ). 1H
NMR (300 MHz) d 0.42 (d, J = 7 Hz, 3H), 0.71 (d, J = 7 Hz, 6H),
0.56–1.57(m, 9H), 3.85 (s, 3H), 4.40, 4.41 (dt, J = 11 Hz, J = 4 Hz,
1H), 4.62–4.79 (m, 2H), 7.20–8.32 (m, 16H). 13C NMR (75 MHz,
CDCl3) (d) 163.9; 161.0 (d, J = 22.5 Hz); 138.8 (d, J = 7.5 Hz);
137.4; 135.6; 134.2 (d, J = 15 Hz); 133.9 (d, J = 7.5 Hz); 132.2 (d,
J = 15 Hz); 132.0 (d, J = 15 Hz); 130.8 (d, J = 15 Hz); 130.6 (d,
J = 7.5 Hz); 129.5; 128.1; 125.8; 125.7 (d, J = 7.5 Hz); 125.2; 121.8
(d, J = 7.5 Hz); 119.9; 118.8 (d, J = 7.5 Hz); 118.2 (d, J = 15 Hz);
117.6; 113.5; 112.3; 78.0; 56.1; 46.4; 39.6; 33.8; 33.6; 32.9;
31.2; 25.7; 22.8; 21.8; 20.8; 15.6.
To the solution of 3-methoxyphenyl(1-naphthyl)phenylphos-
phine (RP)-1 0.21 g (0.6 mmol) in CH2Cl2 (20 mL) was added 30%
aq H2O2 (2 mL). The mixture was stirred at room temperature for
24 h. The phases were separated and the organic phase was washed
twice with 15 mL of water. The organic phase was separated, dried
over anhydrous magnesium sulfate, filtered, and evaporated. The
crude product was purified by silica gel chromatography with
acetone (20%)–dichloromethane (80%) as eluent to give 0.21 g (99%
yield) of >97% enantiomerically pure 3-methoxyphenyl(1-naph-
thyl)phenylphosphine oxide (SP)-4. Mp = 143–145 °C. Anal. Calcd
for C23H19OP (358.37): C, 77.08; H, 5.34. Found: C, 76.71; H, 5.29.
[a]
D = +3.1 (c 1.0, CH2Cl2).31P NMR (121.5 MHz) d 32.82 (s). 1H
4.4. 3-Methoxyphenyl(1-naphthyl)phenylphosphine oxide (RP)-4
NMR (300 MHz) d 3.79 (s, 3H), 7.05–8.61 (m, 16H). 31P NMR
(121.5 MHz) (d 32.82 (s). 1H NMR (300 MHz) (d 3.79 (s, 3H), 7.05–
8.61 (m, 16H). 13C NMR (75 MHz, CDCl3) (d) 159.8 (d, J = 15 Hz);
134.0; 133.8 (d, J = 15 Hz); 133.4; 132.2 (d, J = 7.5 Hz); 132; 129.7;
128.6 (d, J = 7.5 Hz); 128.7 (d, J = 7.5 Hz); 127.4; 126.6; 124.4 (d,
J = 15 Hz); 124.2 (d, J = 15 Hz); 118.3 (d, J = 7.5 Hz); 116.8 (d,
J = 15 Hz); 55.5.
A 50% dispersion in oil of 0.75 g (0.155 mol) of sodium hydride
was added portionwise to the solution of 10.5 g (0.153 mol) of
phosphonium salt in 100 mL dry tetrahydrofurane under argon in
a Schlenk-type flask. After completion of the addition to the reac-
tion solution was added dropwise 3.2 g (0.031 mol) of benzalde-
hyde. After an additional stirring period of 22 h, the reaction
mixture was evaporated and 100 mL of CH2Cl2 was added. The or-
ganic phase was washed twice with 30 mL of water. The organic
phase was separated, dried over anhydrous magnesium sulfate,
filtered, and evaporated. The resulting crude product was purified
by silica gel chromatography with acetone (20%)–dichloromethane
(80%) as an eluent to give 5.2 g (95% yield) of >99% enantiomericaly
pure14 3-methoxyphenyl(1-naphthyl)phenylphosphine oxide (RP)-
4. Mp = 143–145 °C. Anal. Calcd for C23H19O2P (358.37): C, 77.08;
4.7. 2-Iodo-3-methoxyphenyl(1-naphthyl)phenylphosphine
oxide (SP)-5
To a solution of (i-Pr)2NH 0.31 g (3.05 mmol) in dry THF (2.5 mL)
was added n-BuLi (2 mL, 1.6 M solution in hexane) at ꢀ78 °C within
15 min. After stirring for 15 min at ꢀ78 °C to ꢀ40 °C, the LDA solu-
tion was cooled again to ꢀ78 °C and added, at ꢀ78 °C over 20 min,
to a flask containing a solution of 3-methoxyphenyl(1-naph-
thyl)phenylphosphine oxide (RP)-4 1.0 g (2.8 mmol) in dry THF
(6 mL). During the addition the mixture turned reddish-brown
and eventually a beige suspension was formed. After stirring for
an additional 15 min at ꢀ78 °C, a solution of I2 0.77 g (3.03 mmol)
in THF (2.8 mL) was added dropwise at ꢀ70 °C. Toward the end of
the addition, the formation of a reddish-brown viscous paste began.
At this point, the mechanical stirrer was stopped, the cooling bath
was removed, and the mixture was allowed to the warm to 0 °C
to obtain a clear red solution. The reaction was quenched by the
addition of an aq Na2S2O3 solution. The aqueous phase was washed
with ethyl acetate and the combined organic phases were washed
with saturated aq NaCl, dried over anhydrous magnesium sulfate,
filtered, and evaporated. The crude product was purified by silica
gel chromatography with acetone (4%)–dichloromethane (96%) as
eluent to give 1.0 g (74% yield) of pure 2-iodo-3-methoxy-
phenyl(1-naphthyl)phenylphosphine oxide (SP)-5. Mp = 138–
140 °C. Anal. Calcd for C23H18IO2P (484.27): C, 57.04; H, 3.75.
H, 5.34. Found: C, 76.71; H, 5.29. [a]
D = +3.2 (c 1.0, CH2Cl2). 31P
NMR (121.5 MHz) (d 32.82 (s). 1H NMR (300 MHz) (d 3.79 (s, 3H),
7.05–8.61 (m, 16H). 13C NMR (75 MHz, CDCl3) (d) 159.8 (d,
J = 15 Hz); 134.0; 133.8 (d, J = 15 Hz); 133.4; 132.2 (d, J = 7.5 Hz);
132; 129.7; 128.6 (d, J = 7.5 Hz); 128.7 (d, J = 7.5 Hz); 127.4;
126.6; 124.4 (d, J = 15 Hz); 124.2 (d, J = 15 Hz); 118.3 (d,
J = 7.5 Hz); 116.8 (d, J = 15 Hz); 55.5.
4.5. 3-Methoxyphenyl(1-naphthyl)phenylphosphine (RP)-1
To a solution of 3-methoxyphenyl(1-naphhthyl) phenylphos-
phine oxide 0.36 g (1 mmol) in dry benzene (25 mL) was added
pirydine 0.25 g (3 mmol) followed by dropwise addition of trichlo-
rosilane 0.41 g (3 mmol). The mixture was heated at reflux for 3 h.
After cooling to room temperature 30% aq NaOH (12 mL) was
added carefully to the opaque mixture, until the organic and aque-
ous layers became clear. After the separation, the aqueous layer
was washed with benzene (2 ꢁ 15 mL), combined organic layers
were washed with H2O (3 ꢁ 10 mL), dried over anhydrous magne-
sium sulfate, filtered, and evaporated. The crude product was
purified by silica gel chromatography with hexane (40%)–dichloro-
Found: C, 57.07; H, 4.21. [
a]
D = ꢀ14.5 (c 1.0, CH2Cl2). 31P NMR
(121.5 MHz) d 37.30 (s). 1H NMR (300 MHz) d 3.91 (s, 3H), 6.76–
8.77 (m, 15H). IR (ATR): 3433 (w), 2924 (m), 1562 (s), 1436 (m),
1266 (s), 1188 (s) cmꢀ1
.

K. Dziuba et al. / Tetrahedron: Asymmetry 21 (2010) 1401–1405
1405
4.8. (6,60-Dimethoxybiphenyl-2,20-diyl)bis(1-naphthyl)
phenylphosphine oxide (Sa,SP,SP)-6
acknowledged. The authors also wish to thank Professor Z. Urbanc-
zyk-Lipkowska of the Institute of Organic Chemistry, PAS, Warsaw,
for the X-ray measurements for compounds (SP)-3 and (Sa,SP,SP)-6.
´
A
mixture of 2-iodo-3-methoxyphenyl(1-naphthyl) phenyl-
phosphine oxide (SP)-5 1 g (2.05 mmol), activated Cu powder
0.4 g (6.2 mmol), and DMF (4 mL) was stirred at 140 °C for 2 h.
The cooled mixture was evaporated to dryness on a rotary evapo-
rator. The residue was treated for a few minutes with hot CH2Cl2,
the solid parts were removed by filtration, and the filtrate was
washed with saturated NH4Cl solution, dried over anhydrous mag-
nesium sulfate, filtered, and evaporated. The crude product was
purified by silica gel chromatography with ethyl alcohol (1%)–chlo-
roform (96%) as eluent to give 0.2 g (27% yield) of pure (6,60-3-
dimethoxybiphenyl-2,20-dyil)bis(1-naphthyl)phenylphosphine oxide
(Sa,SP,SP)-6. Mp = 189–191 °C. Anal. Calcd for C46H36O4P2 + MeOH
(746.77): C, 75.59; H, 5.40. Found: C, 75.43; H, 5.36. MS m/z: 737
References
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32.98 (s). 1H NMR (300 MHz) d 1.64 (s, 3H), 3.29 (s, 3H), 6.71–
8.62 (m, 30H). IR (ATR): 3392 (w), 3005 (m), 1568 (s), 1435 (m)
1259 (s), 1188 (s) cmꢀ1
.
5. (a) Hayashi, T.; Mise, T.; Fukushima, M.; Kagotani, M.; Nagashima, N.; Hamada,
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4.9. X-ray crystallography
4.9.1. General information
Data sets were collected with a Bruker Kappa Appex II diffrac-
tometer using CuKa radiation. CCDC 767605 (SP)-3 and CCDC
767838 (Sa,SP,SP)-6 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge at
www.ccdc.cam.ac.uk/conts/retriving.html [or from the Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ,
UK, fax: +44(1223)336 033, E-mail: deposit@ccdc.cam.ac.uk].
4.9.2. X-ray crystal structure analysis of (SP)-3
Formula
0.49 ꢁ 0.385 ꢁ 0.315 mm, a = 8.945(1), b = 20.195(1), c = 9.932(1)
Å, b = 107.25, monoclinic, space group P21, V = 1713.3(2) Å3, qcalcd
1.324 Mg/m3, = 1.733 mmꢀ1, Z = 2, k = 1.54184 Å, T = 293(2) K,
C35H40F6O3P2,
M = 684.63,
colorless
crystal
=
l
3786 reflections collected, 2451 independent (Rint = 0.054), 2451
observed reflections, 416 refined parameters, R1 = 0.0757,
wR2 = 0.1898, Flack parameter 0.01(7), residual electron density
0.565 (ꢀ0.260) eÅꢀ3
.
11. (a) Pietrusiewicz, K. M. Phosphorus, Sulfur Silicon 1996, 109–110, 573; (b)
Pakulski, Z.; Demchuk, O. M.; Frelek, J.; Luboradzki, R.; Pietrusiewicz, K. M. Eur.
J. Org. Chem. 2004, 3913.
4.9.3. X-ray crystal structure analysis(Sa,SP,SP)-6
Formula
0.42 ꢁ 0.42 ꢁ 0.42 mm, orthorhombic, space group P21212, a =
15.304(3), b = 18.190(4), c = 8.725(2) Å, V = 2428.9(9) Å3, qcalcd
1.326 Mg/m3, = 4.187 mmꢀ1, Z = 2, k = 1.54178 Å, T = 293(2) K,
C46H36O4P2ꢂ3(CH2Cl2), M = 969.52, colorless crystal
12. Enantiomeric purity of (RP)-4 was conveniently assessed by 1H and 31P
NMR methods using (S)-N-(3,5-dinitrobenzoyl)-1-(1-naphthyl)amine as the
chiral shift reagent: (a) Dunach, E.; Kagan, H. B. Tetrahedron Lett. 1985, 26,
=
l
´
2649; (b) Pakulski, Z.; Demchuk, O.; Kwiatosz, R.; Osinski, P.;
3163 reflections collected, 2808 independent (Rint = 0.065), 1310
observed reflections, 277 refined parameters, R1 = 0.0888, wR2 =
0.2178, Flack parameter ꢀ0.09(6), residual electron density 0.345
´
Swierczyn´ ska, W.; Pietrusiewicz, K. M. Tetrahedron: Asymmetry 2003, 14,
1459.
13. Blade-Font, A.; Vander Werf, C. A.; McEwen, W. . E. J. Am. Chem. Soc. 1960, 82,
2396.
14. Horner, L.; Winkler, H.; Rapp, A.; Mentrup, A.; Hoffmann, H.; Beck, P.
Tetrahedron Lett. 1961, 161.
(ꢀ0.430) eÅꢀ3
.
15. For a recent review, see: Hassan, J.; Sevignon, M.; Gozzi, C.; Schulz, E.; Lemaire,
M. Chem. Rev. 2002, 102, 1359.
Acknowledgments
16. The diastereomeric as well as the enantiomeric purity of the biphenyl product
was determined by HPLC using (R,R)-DACH DNB column with CHCl3–MeOH
98:2 solvent mixture as eluent.
The financial support of this study by the State Committee for
Scientific Research, Poland, Grant No. PBZ 6.03, is gratefully