Kinetic resolution of racemic ferrocenylphosphine compounds by enantioselective oxidation using cyclic selenoxides having a chiral ligand

Article abstract of DOI:10.1246/bcsj.76.381

Cyclic selenoxides having an optically active binaphthyl skeleton work as the reagents for enantioselective oxidation of phosphines to the corresponding phosphine oxides. Treatment of a racemic 2-oxazolin-2-ylferrocenylphosphine with one of the selenoxides in carbon tetrachloride in the presence of phenol affords the corresponding phosphine oxide together with the unreacted starting phosphine, both with moderate enantioselectivities (the phosphine oxide, up to 13% ee; the phosphine, up to 29% ee).

Full text of DOI:10.1246/bcsj.76.381

c. Jpn.
© 2003 The Chemical Society of Japan
Bull. Chem. Soc. Jpn., 76, 381–387 (2003)
381
e Chemical
ciety of Ja-
n
e Chemical
ciety of Ja-
n
Kinetic Resolution of Racemic Ferrocenylphosphine Compounds by
Enantioselective Oxidation Using Cyclic Selenoxides Having a Chiral
Ligand
Kinetic Resolution of Racemic Phosphines
Y. Miyake et al.
03
1
Yoshihiro Miyake, Akiyoshi Yamauchi, Yoshiaki Nishibayashi, and Sakae Uemura*
7
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University,
Sakyo-ku, Kyoto 606-8501
SJA8
09-2673
235
(Received August 19, 2002)
02
Cyclic selenoxides having an optically active binaphthyl skeleton work as the reagents for enantioselective oxida-
tion of phosphines to the corresponding phosphine oxides. Treatment of a racemic 2-oxazolin-2-ylferrocenylphosphine
with one of the selenoxides in carbon tetrachloride in the presence of phenol affords the corresponding phosphine oxide
together with the unreacted starting phosphine, both with moderate enantioselectivities (the phosphine oxide, up to 13%
ee; the phosphine, up to 29% ee).
02
0.3
Ferrocene and its derivatives play an important role in many
areas of synthetic and material chemistry, and thus, they have
been incorporated into complex structures which display un-
usual properties.1 From the viewpoint of stereochemistry, fer-
rocenes with planar chirality have been widely investigated.
They are of increasing importance as chiral ligands in transi-
tion metal-catalyzed asymmetric reactions.2 Ferrocenes with
Scheme 1.
planar chirality have mainly been prepared by two methods:
the optical resolution of racemic ferrocenes and the diastereo-
selective ortho-lithiation of ferrocenes having an optically
active directing group.3 Recently, several groups have reported
examples of direct asymmetric synthesis of ferrocenes bearing
only planar chirality, where the enantioselective ortho-lithia-
tion of prochiral ferrocenes4 and enantioselective intramolecu-
lar insertion of carbenoids into C–H bonds of ferrocenes5 have
been investigated.
Organic selenoxides are known to be the reagents for oxida-
tion of phosphines to the corresponding phosphine oxides.6
However, no successful report on the enantioselective oxida-
tion of racemic phosphines using selenoxides has appeared so
far.7 We now report the preparation of cyclic selenoxides 1
having an optically active binaphthyl skeleton8 and the appli-
cation of 1 to the kinetic resolution of racemic ferrocenylphos-
phine compounds with planar chirality, namely enantioselec-
tive oxidation of the phosphine compounds.
Fig. 1. An ORTEP drawing of 1a. Selected bond lengths,
torsion angle (Å, deg): Se1-O1 = 1.642 (9); C1-C2-C3-C4
= −68.0 (2).
Results and Discussion
At first, we designed and prepared C2-symmetric cyclic
selenides having an optically active binaphthyl skeleton and
converted them into the corresponding selenoxides (Scheme
1). In these selenoxides, it might not be necessary to consider
the configuration around the selenium atom at the oxidation
step because of the C2-symmetric binaphthyl skeleton.9 The
dibromides 2 were prepared from the corresponding (R)-
BINOLs10 in three steps according to the literature method.11
The reaction of 2 with selenium anion afforded the corre-
sponding cyclic selenides 3, which were then oxidized with m-
chloroperbenzoic acid (mCPBA) to the selenoxides 1 having
an optically active binaphthyl skeleton, in good yields. The
molecular structure of the selenoxide 1a was unambiguously
clarified by X-ray structural determination, an ORTEP drawing
being shown in Fig. 1.
First, we investigated kinetic resolution of racemic 2-
oxazolin-2-ylferrocenylphosphine 4a using the selenoxide 1a
(Scheme 2). Typical results are shown in Table 1. The reac-

382 Bull. Chem. Soc. Jpn., 76, No. 2 (2003)
Kinetic Resolution of Racemic Phosphines
Scheme 2.
Table 1. Kinetic Resolution of Oxazolinylferrocenylphosphine 4a Using 1a)
4a
5a
Entry
Additive
Recovered yield (%)b)
Ee (%)c),d)
Yield (%)b) Ee (%)c),e)
1
2
3
—
H2O
TfOH
Pyridine•HCl
PhOH
PhOH
6a
35
26
41
44
48
45
26
31
36
36
33
30
37
34
33
15
19
4
53
51
58
56
52
35
45
53
56
57
55
49
49
50
45
12
6
5
4
17
29
18
19
16
12
18
15
13
9
8
5f)
6g)
7
13
15
5
7
8
11
9
8
8
6
8
9
6b
6c
6d
6e
6f
6g
6h
PhOH
10
11
12
13
14
15h)
8
1
1
a) Reaction conditions: 4a (0.2 mmol), 1a (0.1 mmol), additive (0.1 mmol), CCl4 (2 mL), at
room temperature for 24 h. b) Determined by 31P-NMR. c) Determined by HPLC analysis
using suitable chiral columns (see experimental section). d) Absolute configuration is S.
e) Absolute configuration is R. f) The efficiency of the kinetic resolution, the kf/ks value,12 is
estimated to be 2.3. g) At 0 °C. h) 1b was used in place of 1a.
tion of the racemic 4a with 1a (0.5 molar amount) in CCl4 at
room temperature for 24 h proceeded smoothly to give the cor-
responding phosphine oxide 5a in 53% yield with 12% ee.
The unreacted phosphine 4a was recovered in 35% yield. It

Y. Miyake et al.
Bull. Chem. Soc. Jpn., 76, No. 2 (2003) 383
Table 2. Kinetic Resolution of 4 Using 1aa)
4
5
Entry
Substrate Additive
Recovered yield (%)b) Ee (%)c)
Yield (%)b) Ee (%)c)
1
2
3
4
4b
4b
4c
4c
4d
4e
4e
4e
4e
—
PhOH
—
PhOH
PhOH
—
—
—
—
42
49
49
67
59
28
48
48
14
9
18
6
47
43
39
33
41
46
41
41
46
13
21
12
22
9
5
6d)
1e)
6f)
7f),g)
8f),h)
9f),i)
1
8
8
3
10
9
13
5
a) Reaction conditions: 4 (0.2 mmol), 1a (0.1 mmol), CCl4 (2 mL), at room temperature for 24
h. b) Determined by 31P-NMR. c) Determined by HPLC analysis using suitable chiral columns.
d) Determined by optical rotation. e) Determined by optical rotation after conversion to the cor-
responding phosphine 4d. f) For 3 h. g) CH2Cl2 was used in place of CCl4. h) ClCH2CH2Cl
was used in place of CCl4. i) C6H5Cl was used in place of CCl4.
was revealed to be an enantiomer rich compound of 15% ee
(Table 1, Entry 1). Then the effect of additives on the enantio-
selectivity of either or both compounds was examined; eventu-
ally it was disclosed that the addition of phenol was slightly
effective for improving it (Table 1, Entries 2–14). Thus, 4a
was recovered with 29% ee and 5a was obtained with 13% ee
(Table 1, Entry 5). The efficiency of the kinetic resolution, the
kf/ks value,12 is estimated to be 2.3. When phenol was added to
the reaction mixture before the addition of racemic 4a, a white
precipitate was produced, while the mixture changed to a clear
solution when the reaction was completed. The white precipi-
tate might be the adduct between 1a and phenol13 and the
existence of interaction such as hydrogen bonding8,14 between
the oxygen atom of 1a and the hydroxy group of phenol was
expected. At present we consider that the interaction may
change the chiral environment around the selenoxide. The
reactions in other solvents such as tetrahydrofuran (THF),
dichloromethane and 1,2-dichloroethane were slow and low
enantioselectivities were obtained. When the selenoxide 1b
was used as an oxidant instead of 1a, no asymmetric induction
occurred, unfortunately (Table 1, Entry 15). In some cases, the
formation of some unidentified products was observed by 31P-
NMR.
Other racemic oxazolinylferrocenylphosphines (4b and 4c)
and N,N-dimethylaminomethylferrocenylphosphine (4d) were
investigated for this kinetic resolution by using 1a. Typical
results are shown in Table 2. In all cases, the addition of phe-
nol was revealed to be slightly effective for enantioselectivity,
but higher enantioselectivity than that obtained using 4a was
not observed. Treatment of racemic 4d under similar reaction
conditions afforded 5d in 41% yield with only 1% ee and the
unreacted 4d was recovered in 59% yield with 6% ee (Table 2,
Entry 5). Interestingly, the reaction of racemic ferrocenyl-
phosphine having a hydroxy group (4e) proceeded faster than
that of 4a (Table 2, Entry 6). The reaction of 4e in a variety of
solvents such as dichloromethane, 1,2-dichloroethane and
chlorobenzene also proceeded smoothly to give 5e, but the
enantioselectivity was lower than that obtained using 4a (Table
2, Entries 7–9). The hydrogen bonding between the oxygen
atom of 1a and the hydroxy group of 4e probably accelerated
Scheme 3.
the reaction rate.
Next, we attempted the kinetic resolution of racemic phos-
phines 7, hoping to obtain P-chiral phosphines, which have
recently been shown to be effective ligands for the rhodium-
catalyzed asymmetric hydrogenation (Scheme 3).15 Treatment
of the racemic methyl(1-naphthyl)phenylphosphine (7a) with
1a (0.5 molar amount) in the presence of phenol (0.5 equiv) in
CCl4 at room temperature for 3 h gave the corresponding phos-
phine oxide 8a in 62% yield with 5% ee. The unreacted phos-
phine 7a was recovered in 38% yield, but only with 5% ee.
Typical results are shown in Table 3. Similarly, no satisfactory
results were obtained in the oxidation of racemic methyl(2-
naphthyl)phenylphosphine (7b) or (2-hydroxy-2,2-diphenyl-
ethyl)methyl(phenyl)phosphine (7c) (Table 3, Entries 3–5).
In summary, we have prepared cyclic selenoxides 1 having
an optically active binaphthyl skeleton and attempted the ki-
netic resolution of racemic ferrocenylphosphine 4 using 1 as
oxidants. Although the enantioselectivity of the produced
phosphine is not yet high (up to 29% ee), this conceptually
novel methodology may be interesting for the preparation of
optically active ferrocene derivatives with only planar chirality.
Experimental
General Procedures. 1H- and 13C-NMR spectra were record-
ed on 300 or 400 and 100 MHz FT-NMR spectrometer, respective-
ly. 31P NMR spectra were recorded on a 160 MHz FT-NMR spec-
trometer using P(OMe)3 as an external standard. 77Se NMR spec-

384 Bull. Chem. Soc. Jpn., 76, No. 2 (2003)
Table 3. Kinetic Resolution of 7 Using 1aa)
Entry Substrate Additive Time (h)
Kinetic Resolution of Racemic Phosphines
7
8
Recovered yield (%)b) Ee (%)c)
Yield (%)b) Ee (%)d)
1
2
3
4
5
7a
7a
7b
7b
7c
—
phenol
—
phenol
—
3
3
3
3
38
37
10
57
22
5
0
16
0
62
63
14
43
30
5
2
—
9
e)
0.1
5
19
a) Reaction conditions: 7 (0.2 mmol), 1a (0.1 mmol), additive (0.1 mmol), CCl4 (2 mL), at room temper-
ature. b) Determined by 31P-NMR. c) Determined by HPLC analysis using suitable chiral columns after
conversion to the corresponding phosphine-borane. Absolute configuration is not determined. d) Deter-
mined by HPLC analysis using suitable chiral columns. Absolute configuration is not determined. e) Not
determined.
tra were recorded on a 76 MHz FT-NMR spectrometer using
Me2Se as an external standard. Chemical shifts are reported in
ppm relative to TMS in the solvents specified. High-resolution
mass spectra (HRMS) were obtained with a JEOL JMS-SX102A
spectrometer. Melting points are uncorrected. Column chro-
matographies on SiO2 were performed with Merck silica gel 60.
HPLC analyses were carried out on a HITACHI L-7100 and an L-
7400 UV detector using Daicel Chiralcel OD, AD, and OJ col-
umns at 30 °C. Elemental analyses were performed at the
Microanalytical Center of Kyoto University. All reactions were
performed in oven-dried or flame-dried glassware under an atmo-
sphere of N2 unless otherwise noted. Solvents and chemicals were
obtained commercially and purified by standard procedures.
Racemic phosphine compounds (4a,16 4b,17 4c,17 4d,18 4e,18,19
7a,20 7b,20 and 7c21) were prepared according to literature proce-
dures. Optically active BINOLs were commercially available
compounds.
5.24%. Calcd for C34H24Se: C, 79.83; H, 4.73%.
Preparation of (R)-3,5-Dihydrodinaphtho[2,1-c:1ꢀ,2ꢀ-e]sele-
nepin 4-Oxide (1a). To a solution of 3a (0.359 g, 1.00 mmol) in
CH2Cl2 (30 mL) were added mCPBA (80%, 0.237 g, 1.1 mmol)
and saturated aqueous K2CO3 solution (6 mL) and the resulting
solution was stirred at room temperature for 10 min. The mixture
was poured into saturated aqueous Na2CO3 solution and extracted
with CH2Cl2 (2 × 30 mL). The combined organic layer was then
dried over MgSO4 and concentrated under vacuum to leave a
crude product. Purification by column chromatography on SiO2
with ethyl acetate/MeOH (1/1) as an eluent gave the title com-
pound 1a (0.336 g, 0.90 mmol, 90%). A white solid; mp 84.2–
85.5 °C; [α]D25 −43.4 (c 0.1, CHCl3); 1H NMR (400 MHz, CDCl3)
δ 3.18 (d, J = 10.8 Hz, 1H), 3.55 (d, J = 12.5 Hz, 1H), 3.81 (d, J
= 12.5 Hz, 1H), 4.36 (d, J = 10.8 Hz, 1H), 7.21–7.34 (m, 4H),
7.48–7.55 (m, 3H), 7.63–7.65 (m, 1H), 7.93–8.04 (m, 4H); 13C
NMR (100 MHz, CDCl3) δ 48.9, 54.2, 126.2, 126.5, 126.9, 126.9,
128.0, 128.3, 128.5, 128.8, 129.0, 129.0, 129.1, 131.8, 132.4,
133.6, 133.7, 134.4, 134.6; 77Se NMR (76 MHz, CDCl3) δ 1033.3.
HRMS m/z Found: 377.0446. Calcd for C22H17OSe M+:
377.0446. Found: C, 69.55. H, 4.73%. Calcd for C22H17OSe: C,
70.40; H, 4.30%.
Preparation of (R)-3,5-Dihydrodinaphtho[2,1-c:1ꢀ,2ꢀ-e]sele-
nepin (3a).
A solution of (R)-2,2ꢀ-bis(bromomethyl)-1,1ꢀ-
binaphthalene (2a)11a (2.640 g, 6.00 mmol) and tert-butyl alcohol
(0.35 mL, 3.00 mmol) in THF (4 mL) was added at room tempera-
ture to Li2Se22 (5.55 mmol) suspended in THF (8 mL), and the
mixture was stirred at room temperature for 12 h. Then the reac-
tion mixture was taken up in Et2O/H2O. After separation, the
aqueous layer was extracted with Et2O (2 × 40 mL). The ether
layer was dried over MgSO4 and concentrated under vacuum.
Purification by column chromatography on SiO2 with hexane/
CH2Cl2 (20/1) as an eluent gave the title compound 3a (1.90 g,
5.29 mmol, 95%): A white solid; mp 169.1–170.0 °C; [α]D25 −7.47
X-ray Structural Analysis of 1a.
Single crystals of 1a
(C22H16OSe•C6H6) suitable for X-ray analysis were prepared by
recrystallization from benzene. Diffraction data were collected on
a Rigaku RAXIS imaging plate area detector with Mo Kα (λ =
0.711 Å) radiation and a graphite monochromator at 23 °C. De-
tails of crystal and data collection parameters are summarized in
Table 4. For a structure analysis and refinement, computations
were performed using the CrystalStructure23 crystallographic soft-
ware package of Molecular Structure. Neutral atom scattering
factors were taken from Ref. 24. Anomalous dispersion effects
were included in Fca2l5c; the values of ∆fꢀ and ∆fꢁ were those of Ref.
26. The structure was solved by direct methods (SIR92). All non-
hydrogen atoms were refined anisotropically. Hydrogen atoms
were included, but not refined.
1
(c 0.1, CHCl3); H NMR (400 MHz, CDCl3) δ 3.46 (d, J = 10.8
Hz, 2H), 3.51 (d, J = 10.8 Hz, 2H), 7.18–7.25 (m, 4H), 7.40–7.45
(m, 2H), 7.54 (d, J = 8.0 and 13.6 Hz, 2H), 7.92 (dd, J = 7.8 and
13.6 Hz, 4H); 13C NMR (100 MHz, CDCl3) δ 24.7, 125.4, 126.1,
126.3, 126.6, 128.2, 129.1, 132.0, 132.8, 133.4, 134.5; 77Se NMR
(76 MHz, CDCl3) δ 438.2. Found: C, 73.50; H, 4.79%. Calcd for
C22H16Se: C, 73.54; H, 4.49%.
(R)-2,6-Diphenyl-3,5-dihydrodinaphtho[2,1-c:1ꢀ,2ꢀ-e]selene-
Crystallographic data have been deposited at the CCDC, 12
Union Road, Cambridge CB2 1EZ, UK and copies can be ob-
tained on request, free of charge, by quoting the publication cita-
tion and the deposition numbers CCDC-196734.
(R)-2,6-Diphenyl-3,5-dihydrodinaphtho[2,1-c:1ꢀ,2ꢀ-e]selene-
pin 4-Oxide (1b). The compound was similarly prepared from
3b. A pale yellow solid; 72%; mp 76.1–77.0 °C; [α]D25 −5.30 (c
0.1, CHCl3); 1H NMR (400 MHz, CDCl3) δ 3.30 (d, J = 12.8 Hz,
1H), 3.35 (d, J = 10.8 Hz, 1H), 4.28 (d, J = 12.8 Hz, 1H), 4.47 (d,
J = 10.8 Hz, 1H), 7.00–8.15 (m, 20H); 13C NMR (100 MHz,
pin (3b). The compound was similarly prepared from 2b.11b
A
pale yellow solid; 43%; mp 175.5–176.1 °C; [α]D25 −66.5 (c 0.1,
CHCl3); 1H NMR (400 MHz, CDCl3) δ 3.38 (d, J = 11.4 Hz, 2H),
3.61 (d, J = 11.4 Hz, 2H), 7.11–7.20 (m, 2H), 7.20–7.27 (m, 2H),
7.35–7.51 (m, 8H), 7.67 (brs, 4H), 7.81–7.92 (m, 4H) ; 13C NMR
(100 MHz, CDCl3) δ 22.2, 125.8, 126.0, 126.7, 127.1, 127.3,
128.1, 128.2, 129.7, 130.1, 131.4, 132.3, 132.5, 134.3, 139.0,
141.2; 77Se NMR (76 MHz, CDCl3) δ 440.6. HRMS m/z Found:
512.1049. Calcd for C34H24Se M+: 512.1046. Found: C, 80.31; H,

Y. Miyake et al.
Bull. Chem. Soc. Jpn., 76, No. 2 (2003) 385
Table 4. Summary of Crystallographic Data of 1a
31P NMR (160 MHz, CDCl3) δ 23.6. HRMS m/z Found: 484.1136.
Calcd for C27H27FeNO2P M+ + H: 484.1129. Found: C, 64.76; H,
5.43; N, 2.63%. Calcd for C27H26FeNO2P•H2O: C, 64.69; H, 5.63;
N, 2.79%. The presence of H2O was confirmed by 1H NMR spec-
troscopy.
[2-(4-Isopropyl-2-oxazolin-2-yl)ferrocenyl]diphenylphos-
phine (4b).17 Enantiomeric excess was determined by Daicel
Chiralcel AD, 30 °C, 0.5 mL/min, hexane/2-propanol = 95/5, t1 =
8.20 min, t2 = 9.82 min.
Empirical formula
C22H16OSe•C6H6
Fw
453.44
Crystal system
Space group
Crystal color
a/Å
orthorhombic
P212121(#19)
colorless
8.0215(7)
b/Å
12.529(1)
c/Å
21.105(2)
2121.1(3)
4
1.420
1.95
928.00
Mo Kα (λ = 0.71069 Å)
graphite monochromated
23.0
ω
55.0
18857
1349
direct methods (SIR92)
full-matrix least squares
287
4.70
0.039; 0.044
0.70
3.58
[2-(4-Isopropyl-2-oxazolin-2-yl)ferrocenyl]diphenylphos-
phine Oxide•H2O (5b•H2O). A reddish brown solid; mp 192.2–
192.5 °C; enantiomeric excess was determined by Daicel Chiral-
cel AD, 30 °C, 1.0 mL/min, hexane/2-propanol = 90/10, t1 =
V/(Å3)
Z
Dcalc/g cm−3
µ(Mo Kα)/cm−1
F(000)
1
31.84 min, t2 = 41.72 min; H NMR (400 MHz, CDCl3) δ 0.61
(brs, 3H), 0.80 (brs, 3H), 1.47–1.53 (m, 1H), 2.05 (br, 2H, H2O),
3.13 (m, 1H), 3.75 (m, 1H), 3.93 (brs, 1H), 4.21 (m, 1H), 4.49 (m,
1H), 4.50 (brs, 5H), 5.07 (brs, 1H), 7.27–7.74 (m, 10H); 31P NMR
(160 MHz, CDCl3) δ 23.7. HRMS m/z Found: 498.1293. Calcd for
C28H29FeNO2P M+ + H: 498.1286. Found: C, 65.28; H, 5.62; N,
2.59%. Calcd for C28H28FeO2P•H2O: C, 65.26; H, 5.87; N, 2.72%.
The presence of H2O was confirmed by 1H NMR spectroscopy.
[2-(4-Benzyl-2-oxazolin-2-yl)ferrocenyl]diphenylphosphine
(4c).17 Enantiomeric excess was determined by Daicel Chiralcel
AD, 30 °C, 0.5 mL/min, hexane/2-propanol = 95/5, t1 = 11.29
min, t2 = 14.78 min.
Radiation
Temp/°C
Scan type
Max. 2θ/°
No. of rflns measd
No. of observns (I > 3.00 σ(I))
Structure soln
Refinement
No. of variables
Reflection/parameter ratio
Residuals: R ; Rw
GOF
[2-(4-Benzyl-2-oxazolin-2-yl)ferrocenyl]diphenylphosphine
Oxide•H2O (5c•H2O). A reddish brown solid; mp 193.2–193.7
°C; enantiomeric excess was determined by Daicel Chiralcel AD,
30 °C, 1.0 mL/min, hexane/2-propanol = 90/10, t1 = 41.11 min, t2
Max shift/error in final cycle
Maximum peak in
1
= 46.72 min; H NMR (400 MHz, CDCl3) δ 1.75 (br, 2H, H2O),
0.58
final diff map (e Å−3
Minimum peak in
)
2.12 (dd, J = 12.3 and 14.7 Hz, 1H), 3.00 (dd, J = 12.3 and 13.6
Hz, 1H), 3.06 (dd, J = 8.0 and 8.4 Hz, 1H), 3.98 (brs, 1H), 4.12
(dd, J = 8.0 and 8.4 Hz, 1H), 4.20 (m, 1H), 4.39 (brs, 1H), 4.50 (s,
5H), 5.05 (brs, 1H), 7.03–7.77 (m, 15H); 31P NMR (160 MHz,
CDCl3) δ 23.7. HRMS m/z Found: 546.1273. Calcd for C32H29-
FeNO2P M+ + H: 546.1286. Found: C, 68.79; H, 5.56; N, 2.40%.
Calcd for C32H28FeNO2P•H2O: C, 68.22; H, 5.37; N, 2.49%. The
presence of H2O was confirmed by 1H NMR spectroscopy.
[2-(N,N-Dimethylaminomethyl)ferrocenyl]diphenylphos-
phine (4d). Enantiomeric excess was determined by optical ro-
tation.18
−0.64
final diff map (e Å−3
)
CDCl3) δ 44.2, 51.3, 126.3, 126.4, 126.6, 126.7, 126.9, 127.1,
127.3, 127.9, 128.2, 128.3, 128.7, 129.3, 129.6, 130.0, 131.3,
131.6, 132.8, 132.9, 135.5, 135.7, 139.4, 140.1, 141.5. Found: C,
77.50; H, 4.84%. Calcd for C34H24OSe: C, 77.41; H, 4.59%.
Typical Procedure for Kinetic Resolution of Racemic Ferro-
cenylphosphine Compounds. A solution of 1a (37.5 mg, 0.1
mmol) and phenol (9.4 mg, 0.1 mmol) in carbon tetrachloride (1
mL) was stirred under nitrogen atmosphere at room temperature.
After 15 min, the racemic 4a (93.5 mg, 0.2 mmol) in carbon tetra-
chloride (1 mL) was added to the solution and the resulting solu-
tion was stirred at room temperature for 24 h. Yields of phosphine
and phosphine oxide were determined by integration of the 31P
resonances against P(OMe)3 added as an internal reference. Puri-
fication of the crude products by SiO2 chromatography gave the
corresponding ferrocenylphosphine and ferrocenylphosphine ox-
ide in a pure form.
[2-(4,4-Dimethyl-2-oxazolin-2-yl)ferrocenyl]diphenylphos-
phine (4a). Enantiomeric excess was determined by Daicel
Chiralcel AD, 30 °C, 0.5 mL/min, hexane/2-propanol = 95/5, t1 =
9.27 (S) min, t2 = 11.28 min (R).16
[2-(4,4-Dimethyl-2-oxazolin-2-yl)ferrocenyl]diphenylphos-
phine Oxide•H2O (5a•H2O). A reddish brown solid; mp 115.1–
116.0 °C; enantiomeric excess was determined by Daicel Chiral-
cel AD, 30 °C, 0.5 mL/min, hexane/2-propanol = 90/10, t1 =
45.77 (S) min, t2 = 48.65 min (R); 1H NMR (400 MHz, CDCl3) δ
1.03 (brs, 3H), 1.19 (brs, 3H), 1.35 (br, 2H, H2O), 2.93 (brs, 1H),
3.95 (brs, 2H), 4.49 (m, 6H), 5.09 (brs, 1H), 7.41–7.70 (m, 10H);
[2-(N,N-Dimethylaminomethyl)ferrocenyl]diphenylphos-
phine Oxide•H2O (5d•H2O). A reddish brown solid; mp 59.2–
59.9 °C; enantiomeric excess of 5d was determined by optical ro-
tation after the reduction of 5d into the corresponding phos-
phine18; 1H NMR (400 MHz, CDCl3) δ 1.96 (s, 6H), 3.00 (br, 2H,
H2O), 3.43 (d, J =13.0, 2H), 3.94 (s, 1H), 4.20 (s, 5H), 4.36 (s,
1H), 4.67 (s, 1H), 7.21–7.92 (m, 10H); 31P NMR (160 MHz,
CDCl3) δ 23.3. HRMS m/z Found: 444.1183. Calcd for C25H27-
FeNOP M+ + H: 444.1180. Found: C, 65.47; H, 5.93; N, 2.70%.
Calcd for C25H26FeNOP•H2O: C, 65.09; H, 6.12; N, 3.04%. The
presence of H2O was confirmed by 1H NMR spectroscopy.
[2-(Hydroxymethyl)ferrocenyl]diphenylphosphine (4e).18,19
Enantiomeric excess was determined by Daicel Chiralcel AD, 30
°C, 0.5 mL/min, hexane/2-propanol = 95/5, t1 = 22.77 min, t2 =
29.04 min.
[2-(Hydroxymethyl)ferrocenyl]diphenylphosphine Oxide•
H2O (5e•H2O). A reddish brown solid; mp 91.5–92.3 °C; enan-
tiomeric excess was determined by Daicel Chiralcel OD, 30 °C,
0.5 mL/min, hexane/2-propanol = 95/5, t1 = 31.96 min, t2 =
37.96 min; 1H NMR (400 MHz, CDCl3) δ 3.93 (s, 1H), 4.24–4.36

386 Bull. Chem. Soc. Jpn., 76, No. 2 (2003)
Kinetic Resolution of Racemic Phosphines
(m, 3H), 4.27 (s, 5H), 4.55 (s, 1H), 5.51 (s, 1H), 7.25–7.81 (m,
10H); 31P NMR (160 MHz, CDCl3) δ 30.9. HRMS m/z Found:
416.0627. Calcd for C23H21FeO2P M+: 416.0629. Found: C,
65.94; H, 5.25%. Calcd for C23H21FeO2P: C, 66.37; H, 5.09%.
Chem., 61, 1172 (1996).
S. Siegel and H.-G. Schmalz, Angew. Chem., Int. Ed. Engl.,
36, 2456 (1997).
5
6
a) M. Mikołajczyk and J. Łuczak, J. Org. Chem., 43, 2132
Methyl(1-naphthyl)phenylphosphine (7a).20
Enantiomeric
(1978). b) J. Drabowicz, J. Łuczak, P. Łyzwa, and M.
Mikołajczyk, Phosphorus, Sulfur, Silicon, Relat. Elem., 143, 136
(1998).
excess of 7a was determined by Daicel Chiralcel OD, 30 °C, 1.0
mL/min, hexane/2-propanol = 90/10, t1 = 6.41 min, t2 = 6.98
min, after the transformation of 7a into the corresponding phos-
phine-borane.20c
7
The example of the enantioselective oxidation of racemic
phosphines with chiral oxoruthenium porphyrins has been report-
ed by Simonneaux et al.; P. L. Maux, H. Bahri, G. Simonneaux,
and L. Toupet, Inorg. Chem., 34, 4691 (1995).
Methyl(1-naphthyl)phenylphosphine Oxide (8a).20 Enanti-
omeric excess was determined by Daicel Chiralcel OJ, 30 °C, 1.0
mL/min, hexane/2-propanol = 90/10, t1 = 33.50 min, t2 = 37.90
min.
8
This work was partly presented at ꢂꢃth International Con-
ference on Phosphorus Chemistry July 29–August 3, 2001 Sendai,
Japan, Abstracts p. 210. Rayner et al. independently reported the
preparation of the selenoxide 1a and its use in the oxidation of sul-
fides; D. J. Procter and C. M. Rayner, Synth. Commun., 30, 2975
(2000).
Methyl(2-naphthyl)phenylphosphine (7b).20 Enantiomeric
excess of 7b was determined by Daicel Chiralcel OD, 30 °C, 1.0
mL/min, hexane/2-propanol = 90/10, t1 = 15.98 min, t2 = 19.80
min, after the transformation of 7b into the corresponding phos-
phine-borane.20c
9
a) F. A. Davis, O. D. Stringer, and R. T. Reddy, Tetra-
Methyl(2-naphthyl)phenylphosphine Oxide (8b).20 Enanti-
omeric excess was determined by Daicel Chiralcel AD, 30 °C, 0.5
mL/min, hexane/2-propanol = 90/10, t1 = 28.78 min, t2 = 32.97
min.
(2-Hydroxy-2,2-diphenylethyl)methyl(phenyl)phosphine
(7c).21 Enantiomeric excess of 7c was determined by Daicel
Chiralcel OD, 30 °C, 0.5 mL/min, hexane/2-propanol = 92/8, t1 =
26.42 min, t2 = 33.54 min, after the transformation of 7c into the
corresponding phosphine-borane.20c
(2-Hydroxy-2,2-diphenylethyl)methyl(phenyl)phosphine
Oxide (8c).21 Enantiomeric excess was determined by Daicel
Chiralcel OD, 30 °C, 0.5 mL/min, hexane/2-propanol = 85/15, t1
= 28.40 min, t2 = 36.18 min.
hedron, 41, 4747 (1985). b) K. B. Sharpless, M. W. Young, and R.
F. Lauer, Tetrahedron Lett., 1973, 1979. c) M. Oki and H.
Iwamura, Tetrahedron Lett., 1966, 2917. d) W. J. Burlant and E. S.
Gould, J. Am. Chem. Soc., 76, 5775 (1954). e) T. W. Campbell, H.
G. Walker, and G. M. Coppinger, Chem. Rev., 50, 279 (1952). f)
W. R. Gaythwaite, J. Kenyon, and H. Phillips, J. Chem. Soc.,
1928, 2280.
10 (R)-3,3ꢀ-Diphenyl-1,1ꢀ-bi-2-naphthol can be prepared from
(R)-BINOL; J. M. Chong, L. Shen, and N. J. Taylor, J. Am. Chem.
Soc., 122, 1822 (2000).
11 a) I. G. Stará, P. Stary, M. Tichy, J. Závada, and P. Fiedler,
J. Org. Chem., 59, 1326 (1994). b) T. Ooi, M. Kameda, and K.
Maruoka, J. Am. Chem. Soc., 121, 6519 (1999).
12 The efficiency of the kinetic resolution is characterized by
kf/ks, the selectivity factor = (rate of fast-reacting enantiomer)/
(rate of slow-reacting enantiomer). For a review, R. Noyori, M.
Tokunaga, and M. Kitamura, Bull. Chem. Soc. Jpn., 68, 36 (1995).
13 When LRMS spectra of the white precipitate were mea-
sured, the fragment peak of 1a (m/z = 512) was obtained.
14 a) The preparation of the salts of selenoxides with sulfonic
acid has been reported and the salts worked as oxidants of sulfides
to sulfoxides; D. J. Procter, M. Thornton-Pett, and C. M. Rayner,
Tetrahedron, 52, 1841 (1996). b) F. Toda and K. Mori, J. Chem.
Soc., Chem. Commun., 1986, 1357.
This work was supported by a Grant-in-Aid for Scientific
Research (Nos. 13305062 and 12750747) from the Ministry of
Education, Science, Sports, and Culture. We also thank Dr.
Izuru Takei at The University of Tokyo for his generous gift of
(S)-4a.
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