N-Aryl indole-derived C-N bond axially chiral phosphine ligands: synthesis and application in palladium-catalyzed asymmetric allylic alkylation

Article abstract of DOI:10.1016/j.tetasy.2010.03.039

N-Aryl indole-derived C-N bond axially chiral phosphine ligands 2a-c were obtained by DDQ oxidation of N-aryl indoline-derived phosphine oxide followed by silane reduction. Resolution of C-N bond atropisomers was achieved by chiral HPLC. The investigation

Full text of DOI:10.1016/j.tetasy.2010.03.039

Tetrahedron: Asymmetry 21 (2010) 711–718
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
N-Aryl indole-derived C–N bond axially chiral phosphine ligands: synthesis
and application in palladium-catalyzed asymmetric allylic alkylation
*
Takashi Mino , Shingo Komatsu, Kazuya Wakui, Haruka Yamada, Hiroaki Saotome, Masami Sakamoto,
Tsutomu Fujita
Department of Applied Chemistry and Biotechnology, Graduate School of Engineering, Chiba University, 1-33, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
N-Aryl indole-derived C–N bond axially chiral phosphine ligands 2a–c were obtained by DDQ oxidation of
N-aryl indoline-derived phosphine oxide followed by silane reduction. Resolution of C–N bond atropi-
somers was achieved by chiral HPLC. The investigation of the rotation barrier for the C–N bond axial sta-
bility of phosphines and the determination of the absolute configuration of 2c are described. Finally, the
ability of the chiral ligand 2c was demonstrated in a palladium-catalyzed asymmetric allylic alkylation
(up to 99% ee).
Received 9 March 2010
Accepted 26 March 2010
Available online 3 May 2010
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
Chiral phosphines are important molecules that effect asym-
metric inductions as ligands for transition metal catalysts.1
C(aryl)–C(aryl) bond axially chiral biaryls2 including BINAP3 are
well established as an important class of ligands for asymmetric
metal-catalyzed reactions.4 For nonbiaryl C–C bond axially chiral
ligands, C(aryl)–C(amide carbonyl) bond axially chiral phosphine
ligands5 and C(aryl)–N(amide or imide) bond axially chiral phos-
phine ligands, such as quinazolinone-containing N-anilide6 and
N-arylimide7 type ligands, have been reported. Although the syn-
thesis of C(aryl)–N(amine) bond axially chiral N-aryl indoles by
the stereoselective SNAr reaction of planar chiral arene Cr-complex
was recently reported by Kamikawa,8 the discovery of C(aryl)–
N(amine) bond axially chiral compounds has rarely been
described.9 Previously, we prepared such compounds using an
approach similar to the synthesis of N-aryl indoline type C(aryl)–
N(amine) bond axially chiral aminophosphine 1.10 We herein
report the synthesis of N-aryl indole type C(aryl)–N(amine) bond
axially chiral phosphines 2 and 3, the investigation of the rotation
barrier for C–N bond axial stability, and an application in a
palladium-catalyzed asymmetric allylic alkylation.
PPh2
N
N
N
R1
R2
PPh2
R
PPh2
Me
*
*
*
1
2
3
a: R1 = OMe, R2 = H
b: R1 = Me, R2 = H
c: R1 = CF3, R2= H
d: R1 = CH2OAc, R2 = H
e: R1- R2 =- (CH)4-
a: R = OMe
b: R = Me
c: R = CF3
phines 1a–c.10 Oxidation of phosphine oxide 4a with DDQ (2,3-di-
chloro-5,6-dicyano-p-benzoquinone) gave the corresponding
N-aryl indole-derived phosphine oxide 5a. This phosphine oxide
was converted into desired phosphine ligand ( )-2a using trichlo-
rosilane–triethylamine in good yield (Scheme 1). Phosphines
( )-2b and ( )-2c were easily prepared in the same manner.
On the other hand, phosphine ( )-3 was prepared from N-(o-tolyl)-
indole 611 via the selective lithiation of indole 6 with n-BuLi–TMEDA
in cyclopentyl methyl ether (CPME) and then treatment with chloro-
diphenylphosphine (Scheme 2).
2. Results and discussion
The X-ray crystallographic analysis of phosphines ( )-2a, ( )-2c,
and ( )-3 was accomplished. ORTEP drawings of ( )-2a, ( )-2c, and
( )-3 are shown in Figures 1–3. In all cases, C–N bonds were
twisted between the aryl ring with diphenylphosphine and the in-
dole ring.
Phosphine ligands 2a–c were easily prepared in two steps from
phosphine oxides 4a–c, which were the intermediates of N-aryl
indoline type C(aryl)–N(amine) bond axially chiral aminophos-
To investigate whether C(aryl)–N(amine) bond axial chirality
exists in phosphines ( )-2a–c and ( )-3, we analytically separated
* Corresponding author. Tel.: +81 43 290 3385; fax: +81 43 290 3401.
E-mail address: tmino@faculty.chiba-u.jp (T. Mino).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.03.039

712
T. Mino et al. / Tetrahedron: Asymmetry 21 (2010) 711–718
N
N
DDQ
R
P(O)Ph2
R
P(O)Ph2
m-Xylene, Δ
4
5
a: 47%, b: 53%, c: 45%
N
HSiCl3, Et3N
R
PPh2
m-Xylene, Δ, Ar
( )-2
a: 81%, b: 98%, c: 87%
a: R = OMe, b: R = Me, c: R = CF3
Scheme 1. Preparation of phosphine ligands ( )-2.
Figure 2. ORTEP drawing of ( )-2c.
PPh2
N
N
1) n-BuLi, TMEDA
Me
Me
2) ClPPh2, Ar
6
( )-3 24%
Scheme 2. Preparation of phosphine ligand ( )-3.
these isomers using HPLC with a chiral stationary phase column. As
a result, we obtained nearly resolved UV plots for phosphines 2a–c
and 3 in addition to a pair of clear positive (+) and negative (ꢀ) CD
trace signals of HPLC run at 270 (( )-2a) or 254 nm (( )-2b, 2c, and
3) (Fig. 4).
This result indicates the existence of a pair of atropisomers in N-
aryl indole type phosphines ( )-2a–c and ( )-3. Resolution of ( )-
2a–c and ( )-3 was achieved using a semi-preparative HPLC with
a chiral stationary phase column (Daicel CHIRALCELÒ OJ). The
enantiomeric purities of both 2a–c and 3 were more than 99% ee
from chiral HPLC analyses.
Figure 3. ORTEP drawing of ( )-3.
We conducted a study on the thermal racemization of C–N bond
axially chiral phosphines 2a–c and 3 and assessed the rate of race-
mization by following the first-order decay in enantiomeric excess
in time at a suitable temperature. A small portion of the solution
of optically active 2a–c and 3 in nonane was removed at regular
intervals and subsequently analyzed for enantiomeric excesses by
chiral HPLC analysis. We repeated the experiment at three temper-
atures and determined the rate constants (krac) of 2a–c and 3 at each
temperature. For example, the rotational barrier (D
Gzrac) of 2c was
found to be 36.9 kcal/mol in nonane at 25 °C based on the Arrhenius
and Eyring equations.12 This result corresponds to a half-life of
approximately 2.06 ꢁ 106 years in nonane at 25 °C (Table 1).
Determination of the absolute configurations of 2 was decided
by a preparation of (aR)-2c from (aR)-1c (Scheme 3). We attempted
the direct preparation of indole type chiral phosphine (aR)-2c from
Figure 1. ORTEP drawing of ( )-2a.

T. Mino et al. / Tetrahedron: Asymmetry 21 (2010) 711–718
713
A
C
B
9.3
17.9
[min]
9.3
17.8
[min]
D
22.5
40.8
[min]
14.8
31.2
[min]
Figure 4. Chiral phase HPLC–UV and –CD charts of ( )-2a–c and ( )-3. (A) ( )-2a (UV 254 nm, CD 270 nm; solvent hexane/EtOH = 70/30; flow 1.0 mL/min). (B) ( )-2b (UV
254 nm, CD 254 nm; solvent hexane/EtOH = 95/5; flow 1.0 mL/min). (C) ( )-2c (UV 254 nm, CD 254 nm; solvent hexane/EtOH = 97/3; flow 0.5 mL/min). (D) ( )-3 (UV 254 nm,
CD 254 nm; solvent hexane/EtOH = 90/10; flow 0.5 mL/min).
Table 1
Thermodynamic parameters of thermal racemization of optically active 2a–c and 3
DDQ
(aR)-2c
Thermodynamic parameter at 25 °C
2a
2b
2c
3
N
m-Xylene,
Δ, Ar
D
D
H (kcal/mol)
S (cal/mol K)
28.0
2.91
27.1
31.7
ꢀ4.67
33.1
45.1
27.5
36.9
2.06 ꢁ 106
24.8
F3C
PPh2
Not obtained
ꢀ20.1
Gzrac (kcal/mol)
30.8
D
Half-life (year)
0.15
3123
64
(aR)-1c
N
>99% ee
F3C
P(O)Ph2
indoline type chiral phosphine (aR)-1c (>99% ee) by DDQ oxidation
of the indoline moiety. Oxidation occurred not only at the indoline
moiety but also at the phosphine moiety, and corresponding N-aryl
indole-derived phosphine oxide (aR)-5c was obtained instead of
chiral phosphine (aR)-2c with slight racemization (95% ee). This
phosphine oxide was converted into the desired phosphine (aR)-
2c (>99% ee: after one recrystallization) using trichlorosilane–tri-
ethylamine in a moderate yield. Although the reaction procedure
was not optimized, N-aryl indole type C(aryl)–N(amine) bond axi-
ally chiral phosphine (aR)-2c was obtained using an alternative
synthetic route without HPLC resolution.
(aR)-5c
51%, 95% ee
N
HSiCl3, Et3N
mother liquor
recrystallization
F3C
PPh2
m-Xylene, Δ, Ar
(aR)-2c
43%, >99% ee
We investigated the ability of chiral phosphines 2 and 3 as chi-
ral ligands for palladium-catalyzed asymmetric allylic alkylation13
using 1,3-diphenyl-2-propenyl acetate 7 with dimethyl malonate
8a. This reaction was carried out in the presence of 2 mol % of
Scheme 3. Preparation of phosphine (aR)-2c from chiral indoline type phosphine
(aR)-1c.
[Pd(g 2 (Pd:2 = 1:1) or 8 mol % of 3
3-C3H5)Cl]2, 4 mol % of
(Pd:3 = 1:2), and a mixture of N,O-bis(trimethylsilyl)acetamide
(BSA) and LiOAc14 as the base (Table 2).
ee) but the yield dropped dramatically. We also investigated the
reaction of diethyl malonate 8b at room temperature. The reaction
gave corresponding product (R)-9b in high enantioselectivity with
high yield (entry 10).
As a result, (S)-product 9 was obtained in a palladium-catalyzed
asymmetric allylic alkylation using (aS)-2 as the chiral ligand. On
the other hand, we previously reported that the antipodal of prod-
uct (R)-9 was obtained in this reaction using (aS)-1.10 On the palla-
dium-catalyzed asymmetric allylic alkylation using chiral ligand 2c
at ꢀ20 °C (entry 9, Table 1), the unreacted acetate 7 was recovered
with product 9a. The kinetic resolution of starting material 7 did
not occur (ꢂ2% ee). The reaction mechanism using N-aryl indole
We investigated the ability of ligands 2a–c in toluene at room
temperature (entries 1–3). When the reaction was carried out
using (aR)-2c as the ligand, the enantioselectivity of product (S)-
9a was higher than in the case of chiral ligands 2a and 2b with
good yield (entry 3 vs entries 1 and 2). With 3 as the chiral ligand,
the enantioselectivity and the yield were decreased (entry 4). We
examined the effect of solvents using chiral ligand (aS)-2c (entries
3, and 5–8). When the reaction was carried out in diethyl ether in-
stead of toluene, the enantioselectivity of (R)-9a slightly increased
to 98.9% ee (entry 5). When the reaction was carried out at ꢀ20 °C
(entry 9), the enantioselectivity of product was not changed (99.0%

714
T. Mino et al. / Tetrahedron: Asymmetry 21 (2010) 711–718
Table 2
Palladium-catalyzed asymmetric allylic alkylation using 2 and 3a
O
O
chiral ligand 2 and 3
[Pd(η3-C3H5)Cl]2
O
O
RO
Ph
OR
OAc
+
OR
RO
Ph
Ph
Ph
LiOAc, BSA, Ar
*
7
8
9
a: R = Me, b: R = Et
Entry
Ligand
R
Solv.
Temp (°C)
Time (h)
Yieldb (%)
ee (%) (config.)c
1
2
(ꢀ)-2a
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
PhMe
PhMe
PhMe
PhMe
Et2O
rt
rt
rt
rt
rt
rt
rt
rt
24
24
24
72
24
24
24
24
48
24
93
96
95
8
96
97
95
98
46
99
94(R)
97(S)
98(S)
50(R)
98.9(R)
98.5(R)
97(R)
(+)-2b
3
(aS)-(+)-2c
(ꢀ)-3
4d
5
(aR)-(ꢀ)-2c
(aR)-(ꢀ)-2c
(aR)-(ꢀ)-2c
(aR)-(ꢀ)-2c
(aR)-(ꢀ)-2c
(aR)-(ꢀ)-2c
6
7
8
9
THF
DCM
MeCN
Et2O
98(R)
ꢀ20
99.0(R)
10
Et2O
rt
99.0(R)e
g
3-C3H5)Cl]2 (2 mol %).
a
b
c
The reactions were carried out with 3.0 equiv of 8 and BSA in the presence of LiOAc (4 mol %) and ligand 2 (4 mol %) and [Pd(
Isolated yields.
Determined by HPLC analysis using a chiral column (Daicel CHIRALCELÒ OD-H).
This reaction was carried out using 8 mol % of (ꢀ)-3 and LiOAc.
d
e
Determined by HPLC analysis using a chiral column (Daicel CHIRALCELÒ OJ).
type ligand 2 was different from the case of N-aryl indoline type li-
gand 1 and resembled the pyrrolidinyl-containing aminophos-
We suggest the plausible asymmetric induction process of pal-
ladium-catalyzed AAA reaction of 7 with 8a using chiral ligand
(aS)-2 in Figure 6. There are two candidates, A and B, which are
possible structures formed from chiral ligand (aS)-2. Intermediate
B could be obtained from A by exchanging the relative positions
of the phosphine and the acetate ligands. However, intermediate
B is unstable because of the steric hindrance between the phenyl
rings of allylic substrate and the indole ring of ligand. Therefore,
the reaction probably proceeds through an M-type intermediate
A rather than a W-type intermediate B. The nucleophilic attack oc-
curs predominantly at the allyl terminus from the trans to the
phosphine atom. As a result, the (S)-product 9a was obtained in
this reaction using the chiral ligand (aS)-2.
phines.15 The
p
–allyl–Pd complex 10 containing the racemic
ligand ( )-2a was synthesized upon the successive treatment of
[Pd(
3-C3H5)Cl]2 with ligand 2a (Pd:2a = 1:1). Its suitable crystal
g
was obtained from hexane–CHCl3 and single crystal X-ray analysis
of 10 was carried out (Fig. 5).
O
C2
3. Conclusions
C1
C3
N
In conclusion, we prepared N-aryl indole type C(aryl)–N(amine)
bond axially chiral phosphines 2a–c and 3 which were resolved by
HPLC over a chiral stationary phase column. We also obtained (aR)-
2c by an alternative synthetic route without HPLC resolution. Our
pilot study disclosed that high enantioselectivity was achieved
with these ligands in a palladium-catalyzed asymmetric allylic
alkylation of 1,3-diphenyl-2-propenyl acetate 7 (up to 99% ee). Fur-
ther studies to explore the scope of these ligands in other asym-
metric catalytic reactions are currently in progress.
Pd
P
Cl
MeO
N
Pd(II)
P
Cl
4. Experimental
4.1. Preparation of phosphine oxide 5a
Figure 5. ORTEP drawing of palladium complex 10. Selected bond lengths (Å) and
angles (°): Pd–P, 2.2984(11); Pd–Cl, 2.3796(13); Pd–C(1), 2.117(5); Pd–C(2),
2.128(6); Pd–C(3), 2.190(5); C(1)–Pd–C(3), 67.6(3); Cl–Pd–P, 94.27(4). The unit
cell contains one solvent molecule (CHCl3). For the purpose of clarity, the solvent
molecule is omitted.
To a mixture of phosphine oxide 4a (0.153 g, 0.36 mmol) and m-
xylene (3 mL) was added DDQ (0.152 g, 0.72 mmol) and then heated
to 130 °C for 2 h. After cooling to room temperature, the mixture was
diluted with ethyl acetate, and filtered though Celite, eluting with
additional ethyl acetate. The filtrate was concentrated under re-
duced pressure. The resulting residue was purified by silica gel chro-
matography (elution with n-hexane/ethyl acetate/triethylamine
= 3:3:1): 0.072 g, 0.17 mmol, 47% as a white solid; mp 163–164 °C;
1H NMR (CDCl3) d 3.60 (s, 3H), 6.32 (d, J = 3.3 Hz, 1H), 6.52 (d,
J = 7.7 Hz, 1H), 6.83–7.05 (m, 5H), 7.17–7.49 (m, 10H), 7.60–7.67
The solid-state structure shows that ligand 2a is coordinated to
palladium atom as the monodentate ligand. The trans influence of
the ligand is reflected in the lengthening of the Pd–C(3) bond in
trans disposition to the phosphine atom to the Pd–C(1) distance
[2.190(5) vs 2.117(5) Å].

T. Mino et al. / Tetrahedron: Asymmetry 21 (2010) 711–718
715
MeOOC
COOMe
R
R
Ph
N
N
Ph
aS
Ph
Ph
OAc
Ph
Pd(II)
OAc
Pd(II)
OAc
Ph
P
P
7
A
B
COOMe
Ph
O
O
MeOOC
R
N
MeO
Ph
OMe
Ph
Pd(0)
Ph
P
(S)-9a
Figure 6. Plausible asymmetric induction process of palladium-catalyzed AAA reaction using chiral ligand (aS)-2.
(m, 2H); 13C NMR (CDCl3) d 56.1, 102.3, 110.9, 116.1 (d, JCP = 2.4 Hz),
119.3, 120.0, 120.9, 126.1 (d, JCP = 9.4 Hz), 127.3, 127.4, 127.8, 128.0,
128.2, 129.1 (d, JCP = 13.95 Hz), 130.1, 130.3, 130.4 (d,
JCP = 106.8 Hz), 130.6, 130.6 (d, JCP = 5.3 Hz), 130.7 (d, JCP = 2.9 Hz),
131.4 (d, JCP = 2.8 Hz), 131.7, 131.7 (d, JCP = 106.3 Hz), 131.8, 134.5
(d, JCP = 98.8 Hz), 136.9, 157.2 (d, JCP = 10.5 Hz); 31P NMR (CDCl3) d
26.1; EI-MS m/z (relative intensity): 423 (M+, 100); HRMS (FAB-
MS) m/z calcd for C27H22O2NP + H 424.1466, found 424.1464.
heated to 80 °C for 3 h. After cooling to room temperature, the mix-
ture was diluted with ethyl acetate, and filtered though Celite,
eluting with additional ethyl acetate. The filtrate was concentrated
under reduced pressure. The resulting residue was purified by sil-
ica gel chromatography (elution with n-hexane/ethyl acetate/tri-
ethylamine = 7:4:1): 1.06 g, 2.31 mmol, 45% as a white solid; mp
78–79 °C; 1H NMR (CDCl3) d 6.33 (dd, J = 0.7 and 3.3 Hz, 1H), 6.39
(d, J = 8.2 Hz, 1H), 6.79 (td, J = 1.0 and 7.1 Hz, 1H), 6.90 (td, J = 0.8
and 7.1 Hz, 1H), 7.02 (d, J = 3.3 Hz, 1H), 7.08–7.14 (m, 2H), 7.20–
7.30 (m, 4H), 7.34–7.41 (m, 3H), 7.47–7.54 (m, 2H), 7.68 (td,
J = 0.9 and 9.3 Hz, 1H), 7.93–8.03 (m, 2H); 13C NMR (CDCl3) d
102.9, 110.9, 119.7, 120.0, 121.4, 122.5 (qd, JCP and JCF = 2.3 and
274.8 Hz), 127.4, 127.8 (d, JCP = 12.4 Hz), 128.3 (d, JCP = 12.2 Hz),
128.9 (d, JCP = 11.8 Hz), 129.8 (d, JCP = 107.8 Hz), 130.0, 130.6,
130.7, 130.8, 131.2 (qd, JCP and JCF = 2.3 and 5.0 Hz), 131.5 (d,
JCP = 1.7 Hz), 131.6 (d, JCP = 9.5 Hz), 131.8 (d, JCP = 2.8 Hz), 132.1
(d, JCP = 7.9 Hz), 137.7 (d, JCP = 97.2 Hz), 138.2 (d, JCP = 9.0 Hz),
138.8, 140.4 (dq, JCP and JCF = 1.6 and 5.5 Hz); 31P NMR (CDCl3) d
25.7; FAB-MS m/z (relative intensity): 461 (M+, 63); HRMS (FAB-
MS) m/z calcd for C27H19ONF3P 461.1156, found 461.1182.
4.2. Preparation of phosphine oxide 5b
To a mixture of phosphine oxide 4b (0.614 g, 1.50 mmol) and m-
xylene (5 mL) was added DDQ (1.73 g, 7.5 mmol) and then heated to
130 °C for 5 d. After cooling to room temperature, the mixture was
diluted with ethyl acetate, and filtered though Celite, eluting with
additional ethyl acetate. The filtrate was concentrated under re-
duced pressure. The resulting residue was purified by silica gel chro-
matography (elution with n-hexane/ethyl acetate/triethylamine
= 6:2:1): 0.324 g, 0.80 mmol, 53% as a white solid; mp 170–171 °C;
1H NMR (CDCl3) d 1.70 (s, 3H), 6.36 (d, J = 3.2 Hz, 1H), 6.42 (d,
J = 8.1 Hz, 1H), 6.81–6.92 (m, 2H), 6.97–7.11 (m, 3H), 7.16 (d,
J = 3.3 Hz, 1H), 7.27–7.32 (m, 3H), 7.35–7.44 (m, 4H), 7.48–7.55
(m, 2H), 7.60–7.67 (m, 2H); 13C NMR (CDCl3) d 17.2 (d, JCP = 1.4 Hz),
102.5, 110.7, 119.5, 120.3, 121.3, 127.4, 127.5, 127.8, 128.0, 128.1 (d,
JCP = 13.8 Hz), 128.2, 129.9, 130.3, 130.4, 130.7 (d, JCP = 105.9 Hz),
130.8 (d, JCP = 2.9 Hz), 131.4 (d, JCP = 3.0 Hz), 131.7, 131.7 (d,
JCP = 106.1 Hz), 131.8, 132.3, 132.4 (d, JCP = 9.5 Hz), 132.4, 133.6 (d,
JCP = 99.8 Hz), 135.0 (d, JCP = 2.2 Hz), 136.3, 139.7 (d, JCP = 6.9 Hz),
140.6 (d, JCP = 4.4 Hz); 31P NMR (CDCl3) d 26.1; EI-MS m/z (relative
intensity): 407 (M+, 100); HRMS (FAB-MS) m/z calcd for C27H22ONP
+ H 408.1517, found 408.1533.
4.4. Preparation of ( )-N-(20-diphenylphosphino-60-methoxy
phenyl)indole ( )-2a
To a mixture of phosphine oxide 5a (0.121 g, 0.3 mmol) and tri-
ethylamine (0.25 mL, 1.8 mmol) in m-xylene (1 mL) was added tri-
chlorosilane (0.18 mL, 1.8 mmol) at 0 °C under an Ar atmosphere.
The reaction mixture was heated to 130 °C for 6 h. After being
cooled to room temperature, the mixture was diluted with chloro-
form and the reaction was quenched with 2 M aqueous NaOH solu-
tion. The organic layer was washed with water and brine, dried
over MgSO4, and concentrated under reduced pressure. The residue
was purified by silica gel chromatography (elution with n-hexane/
ethyl acetate = 15:1): 0.098 g, 0.24 mmol, 81% as a white solid, mp
146–148 °C; 1H NMR (CDCl3) d 3.65 (s, 3H), 6.51 (d, J = 3.2 Hz, 1H),
6.69 (ddd, J = 7.7, 3.0 and 1.2 Hz, 1H), 6.77–6.81 (m, 2H), 6.98–7.38
4.3. Preparation of phosphine oxide 5c
To a mixture of phosphine oxide 4c (2.38 g, 5.14 mmol) and m-
xylene (14 mL) was added DDQ (2.34 g, 11.7 mmol) and then

716
T. Mino et al. / Tetrahedron: Asymmetry 21 (2010) 711–718
(m, 14H), 7.57–7.60 (m, 1H); 13C NMR (CDCl3) d 55.9, 102.1, 110.7,
110.7, 112.5, 119.5, 120.4, 121.5, 125.7, 127.9, 128.1, 128.2, 128.4,
128.5, 128.6, 128.7, 129.4, 129.5, 129.6,131.4 (d, JCP = 3.2 Hz),
133.7, 134.0, 136.5 (d, JCP = 5.3 Hz), 136.5 (d, JCP = 2.3 Hz), 137.1,
140.5 (d, JCP = 2.2 Hz), 156.6 (d, JCP = 0.6 Hz); 31P NMR (CDCl3) d
ꢀ16.2; EI-MS m/z (relative intensity): 407 (M+, 15); HRMS (FAB-
MS) m/z calcd for C27H22ONP 407.1439, found 407.1461; HPLC Dai-
cel CHIRALCELÒ OJ (0.46 u ꢁ 25 cm, UV 254 nm, n-hexane/etha-
138.1, 138.6, 141.1 (qd, JCP and JCF = 1.7 and 27.2 Hz), 143.9 (d,
JCP = 19.9 Hz); 31P NMR (CDCl3) d ꢀ17.4; FAB-MS m/z (relative
intensity): 445 (M+, 100); HRMS (FAB-MS) m/z calcd for
C27H19NF3P 445.1207, found 445.1205; HPLC Daicel CHIRALCELÒ
OJ (0.46 u ꢁ 25 cm, UV 254 nm, n-hexane/ethanol = 97:3, 0.5 mL/
min), tR = 22.5 (CD, kext (De) 254 (+)) and 40.8 (CD, kext (De) 254
(ꢀ)) min; X-ray diffraction analysis data of ( )-2c (Fig. 2). Colorless
prismatic crystals from n-hexane–chloroform, monoclinic space
ꢀ
nol = 70:30, 1.0 mL/min), tR = 9.3 (CD, kext
(D
e) 270 (ꢀ)) and 17.9
group P1, a = 9.4193(13) Å, b = 10.7966(14) Å, c = 11.4274(15) Å,
(CD, kext ) 270 (+)) min; X-ray diffraction analysis data of ( )-
(D
e
a
= 109.707(2)°, b = 90.486(2)°,
c
= 97.413(2)°, V = 1083.2(2) Å3,
2a (Fig. 1). Colorless prismatic crystals from n-hexane–chloroform,
Z = 2, (Mo Ka
q
= 1.366 g/cm3, ) = 1.67 cmꢀ1. The structure was
l
monoclinic space group P21/n, a = 12.6654(7) Å, b = 8.0543(5) Å,
solved by the direct method of full-matrix least–squares, where
c = 20.9933(12) Å,
a
= 90°, b = 98.3380(10)°,
c
= 90°, V = 2118.9(2)
the final R and Rw were 0.0341 and 0.0891 for 4103, respectively.
Å3, Z = 4, = 1.277 Mg/m3,
q
l
(Mo K
a
) = 1.48 cmꢀ1. The structure
was solved by the direct method of full-matrix least-squares,
where the final R and Rw were 0.1050 and 0.2631 for 11517 reflec-
tions, respectively.
4.7. Preparation of ( )-N-(20-methylphenyl)-2-diphenyl
phosphinoindole ( )-3
To
a
mixture of N-(20-methylphenyl)indole
6
(0.609 g,
4.5. Preparation of ( )-N-(20-diphenylphosphino-60-
2.94 mmol) and TMEDA (0.50 mL, 3.31 mmol) in CPME (12 mL)
was added dropwise n-BuLi in n-hexane (2.09 mL, 3.30 mmol,
1.58 M) over 10 min. The mixture was stirred at 50 °C for 3 h then
treated with chlorodiphenylphosphine (0.61 mL, 3.30 mmol) and
stirring was continued for 20 h at room temperature. The reaction
was quenched with saturated aqueous NH4Cl and the reaction mix-
ture was diluted with diethyl ether. The organic layer was washed
with water and brine, dried over MgSO4, and concentrated under
reduced pressure. The residue was purified by silica gel chroma-
tography (elution with chloroform/ethyl acetate = 8:1): 0.271 g,
0.69 mmol, 24% as a white solid, mp 124–125 °C; 1H NMR (CDCl3)
d 1.86 (s, 3H), 6.36 (d, J = 0.6 Hz, 1H), 6.83–6.86 (m, 1H), 6.92 (d,
J = 7.8 Hz, 1H), 7.06–7.12 (m, 3H), 7.27–7.37 (m, 12H), 7.56–7.59
(m, 1H); 13C NMR (CDCl3) d 17.6 (d, JCP = 4.1 Hz), 110.4 (d,
JCP = 1.3 Hz), 111.1, 120.0, 120.5, 122.5, 126.3, 127.9 (d,
JCP = 1.5 Hz), 128.3, 128.4, 128.9, 128.9, 130.0 (d, JCP = 2.7 Hz),
130.7, 133.7, 134.0, 135.6 (d, JCP = 12.2 Hz), 135.7 (d, JCP = 10.8 Hz),
136.7 (d, JCP = 2.3 Hz), 137.4, 138.6 (d, JCP = 3.2 Hz), 140.3 (d,
JCP = 2.8 Hz); 31P NMR (CDCl3) d ꢀ27.2; EI-MS m/z (relative inten-
sity): 391 (M+, 32); HRMS (FAB-MS) m/z calcd for C27H22NP
391.1490, found 391.1486; HPLC Daicel CHIRALCELÒ OJ (0.46
u ꢁ 25 cm, UV 254 nm, n-hexane/ethanol = 90:10, 0.5 mL/min),
methylphenyl)indole ( )-2b
To a mixture of phosphine oxide 5b (0.109 g, 0.27 mmol) and
triethylamine (0.23 mL, 1.62 mmol) in m-xylene (1 mL) was added
trichlorosilane (0.16 mL, 1.62 mmol) at 0 °C under an Ar atmo-
sphere. The reaction mixture was heated to 120 °C for 6 h. After
being cooled to room temperature, the mixture was diluted with
chloroform and the reaction was quenched with 2 M aqueous
NaOH solution. The organic layer was washed with water and
brine, dried over MgSO4, and concentrated under reduced pressure.
The residue was purified by silica gel chromatography (elution
with n-hexane/ethyl acetate = 15:1): 0.102 g, 0.26 mmol, 98% as a
white solid, mp 115–116 °C; 1H NMR (CDCl3) d 1.84 (s, 3H), 6.53
(d, J = 3.1 Hz, 1H), 6.72–6.74 (m, 2H), 6.95–7.11 (m, 5H), 7.16–
7.23 (m, 5H), 7.30–7.33 (m, 5H), 7.61 (d, J = 7.5 Hz, 1H); 13C NMR
(CDCl3) d 17.2, 102.2, 110.5, 119.7, 120.6, 121.8, 127.8, 128.2,
128.3, 128.4, 128.5, 128.6, 128.7 (d, JCP = 1.8 Hz), 128.8, 131.5,
131.9, 133.7 (d, JCP = 2.3 Hz), 133.9 (d, JCP = 2.8 Hz), 136.5, 136.7,
137.1 (d, JCP = 12.1 Hz), 137.9 (d, JCP = 2.7 Hz), 139.1 (d,
JCP = 15.1 Hz); 31P NMR (CDCl3) d ꢀ16.5; FAB-MS m/z (relative
intensity): 391 (M+, 53); HRMS (FAB-MS) m/z calcd for C27H22NP
391.1490, found 391.1476; HPLC Daicel CHIRALCELÒ OJ (0.46
u ꢁ 25 cm, UV 254 nm, n-hexane/ethanol = 95:5, 1.0 mL/min),
tR = 14.8 (CD, kext
(D
e
) 254 (+)) and 31.2 (CD, kext
(D
e) 254 (ꢀ))
min; X-ray diffraction analysis data of ( )-3 (Fig. 3). Colorless pris-
matic crystals from hexane–chloroform, monoclinic space group
P21/C, a = 10.488(3) Å, b = 18.091(5) Å, c = 11.346(4) Å,
tR = 9.3 (CD, kext
(D
e
) 254 (ꢀ)) and 17.8 (CD, kext
(De) 254 (+)) min.
4.6. Preparation of ( )-N-(20-diphenylphosphino-60-trifluoro
methylphenyl)indole ( )-2c
b = 92.23(3)°, V = 2151.2(12) Å3, Z = 4, = 1.209 g/cm3,
q l (Cu Ka)
= 1.21 cmꢀ1. The structure was solved by the direct method of
full-matrix least–squares, where the final R and Rw were 0.038
and 0.139 for 3175 reflections, respectively.
To a mixture of phosphine oxide 5c (0.461 g, 1.0 mmol) and tri-
ethylamine (0.84 mL, 6.0 mmol) in m-xylene (2 mL) was added tri-
chlorosilane (0.61 mL, 6.0 mmol) at 0 °C under an Ar atmosphere.
The reaction mixture was heated to 120 °C for 6 h. After being
cooled to room temperature, the mixture was diluted with chloro-
form and the reaction was quenched with 2 M aqueous NaOH solu-
tion. The organic layer was washed with water and brine, dried
over MgSO4, and concentrated under reduced pressure. The residue
was purified by silica gel chromatography (elution with n-hexane/
ethyl acetate = 15:1): 0.388 g, 0.87 mmol, 87% as a white solid, mp
135–136 °C; 1H NMR (CDCl3) d 6.55 (dd, J = 3.2 and 0.8 Hz, 1H),
6.68 (d, J = 8.1 Hz, 1H), 6.74 (d, J = 3.2 Hz, 1H), 6.96–7.13 (m, 6H),
7.19–7.39 (m, 7H), 7.54 (td, J = 7.8 and 0.6 Hz, 1H), 7.62 (d,
J = 7.8 Hz, 1H), 7.83 (dd, J = 7.9 and 1.2 Hz, 1H); 13C NMR (CDCl3)
d 102.8, 110.8 (d, JCP = 1.5 Hz), 119.9, 120.5, 122.0, 122.9 (qd, JCP
and JCF = 2.2 and 274.2 Hz), 127.7 (q, JCF = 5.1 Hz), 127.7, 128.5 (d,
JCP = 6.9 Hz), 128.6 (d, JCP = 7.1 Hz), 129.0, 129.1, 130.0, 130.4 (qd,
JCP and JCF = 3.2 and 31.0 Hz), 133.6 (d, JCP = 20.6 Hz), 133.7 (d,
JCP = 20.9 Hz), 135.5 (d, JCP = 12.4 Hz), 136.2 (d, JCP = 12.1 Hz),
4.8. Resolution of ( )-2a
HPLC resolution of ( )-2a (8.0 mg) dissolved in EtOH (2.5 mL)
was carried out by successive injections of 0.5 mL on a CHIRALCELÒ
OJ (1.0 u ꢁ 25 cm). A mixture of n-hexane/ethanol = 70:30 was
used as the eluent working at a flow rate of 1.0 mL/min and with
UV monitoring at 254 nm. Enantiomerically pure (ꢀ)-2a (3.2 mg)
and (+)-2a (3.1 mg) were, respectively, obtained by evaporation
of fractions.
Compound (ꢀ)-2a: >99% ee; ½a D20
¼ ꢀ55:4 (c 0.25, CHCl3); HPLC
ꢃ
(Daicel CHIRALCELÒ OJ (0.46 u ꢁ 25 cm, UV 254 nm, n-hexane/eth-
anol = 70:30, 1.0 mL/min), tR = 7.8 min; 1H NMR and 31P NMR data
were identical to those of ( )-2a.
Compound (+)-2a: >99% ee; ½a D20
¼ þ53:0 (c 0.22, CHCl3); HPLC
ꢃ
(Daicel CHIRALCELÒ OJ (0.46 u ꢁ 25 cm, UV 254 nm, n-hexane/eth-
anol = 70:30, 1.0 mL/min), tR = 14.0 min; 1H NMR and 31P NMR
data were identical to those of ( )-2a.

T. Mino et al. / Tetrahedron: Asymmetry 21 (2010) 711–718
717
4.9. Resolution of ( )-2b
heated to 80 °C for 1.5 h. After cooling to room temperature, the
mixture was diluted with diethyl ether and water. The organic
layer was washed with brine, dried over MgSO4, and concentrated
under reduced pressure. The residue was purified by silica gel
chromatography (elution with n-hexane/ethyl acetate/triethyl-
amine = 7:4:1): 0.057 g, 0.12 mmol, 51% as a white solid; 94.9%
HPLC resolution of ( )-2b (10.0 mg) dissolved in ethanol
(2.5 mL) was carried out by successive injections of 0.5 mL on a
CHIRALCELÒ OJ (1.0 u ꢁ 25 cm). A mixture of n-hexane/etha-
nol = 90:10 was used as the eluent working at a flow rate of
2.0 mL/min and with UV monitoring at 254 nm. Enantiomerically
pure (ꢀ)-2b (4.8 mg) and (+)-2b (4.3 mg) were, respectively, ob-
tained by evaporation of fractions.
ee; ½a 2D0
ꢃ
¼ ꢀ170:4 (c 0.73, CHCl3); HPLC (Daicel CHIRALCELÒ OJ-H
(0.46 u ꢁ 25 cm, UV 254 nm, n-hexane/ethanol = 92:8, 0.3 mL/
min), tR = 33.8 (major) and 54.4 min (minor); 1H NMR and 31P
NMR data were identical to those of ( )-5c.
Compound (ꢀ)-2b: >99% ee; ½a D25
¼ ꢀ125:0 (c 0.50, CHCl3);
ꢃ
HPLC (Daicel CHIRALCELÒ OJ (0.46 u ꢁ 25 cm, UV 254 nm, n-hex-
ane/ethanol = 95:5, 1.0 mL/min), tR = 7.8 min; 1H NMR and 31P
NMR data were identical to those of ( )-2b.
4.14. Preparation of (aR)-(ꢀ)-2c
Compound (+)-2b: >99% ee; ½a D25
ꢃ
¼ þ126:9 (c 0.50, CHCl3);
To a mixture of (aR)-5c (0.048 g, 0.10 mmol, 95% ee) and trieth-
ylamine (0.087 mL, 0.62 mmol) in m-xylene (0.6 mL) was added
trichlorosilane (0.063 mL, 0.62 mmol) at 0 °C under an Ar atmo-
sphere. The reaction mixture was heated to 120 °C for 6 h. After
being cooled to room temperature, the mixture was diluted with
diethyl ether and the reaction was quenched with 2 M aqueous
NaOH solution. The organic layer was washed with brine, dried
over MgSO4, and concentrated under reduced pressure. The residue
was purified by silica gel chromatography (elution with n-hexane/
ethyl acetate = 15:1) and recrystallized in n-hexane–chloroform at
ꢀ20 °C. After filtration, the motherliquor was concentrated with a
rotary evaporator: 0.020 g, 0.04 mmol, 43% as a white solid; >99%
ee; HPLC Daicel CHIRALCELÒ OJ (0.46 u ꢁ 25 cm, UV 254 nm, n-
hexane/ethanol = 97:3, 0.5 mL/min), tR = 32.9 (minor) and 61.6
(major); 1H NMR and 31P NMR data were identical to those of
( )-2c.
HPLC (Daicel CHIRALCELÒ OJ (0.46 u ꢁ 25 cm, UV 254 nm, n-hex-
ane/ethanol = 95:5, 1.0 mL/min), tR = 15.1 min; 1H NMR and 31P
NMR data were identical to those of ( )-2b.
4.10. Resolution of ( )-2c
HPLC resolution of ( )-2c (90.7 mg) dissolved in ethanol
(18.0 mL) was carried out by successive injections of 0.5 mL on a
CHIRALCELÒ OJ (1.0 u ꢁ 25 cm). A mixture of n-hexane/etha-
nol = 97:3 was used as the eluent working at a flow rate of
1.0 mL/min and with UV monitoring at 254 nm. Enantiomerically
pure (aS)-(+)-2c (36.3 mg) and (aR)-(ꢀ)-2c (35.3 mg) were, respec-
tively, obtained by evaporation of fractions.
Compound (aS)-(+)-2c: >99% ee; ½a D20
¼ þ183:0 (c 0.20, CHCl3);
ꢃ
HPLC (Daicel CHIRALCELÒ OJ (0.46 u ꢁ 25 cm, UV 254 nm, n-hex-
ane/ethanol = 97:3, 0.5 mL/min), tR = 22.9 min; 1H NMR and 31P
NMR data were identical to those of ( )-2c.
4.15. General procedure for the palladium-catalyzed allylic
alkylation
Compound (aR)- (ꢀ)-2c: >99% ee; ½a 20
¼ ꢀ183:4 (c 0.20, CHCl3);
ꢃ
HPLC (Daicel CHIRALCELÒ OJ (0.46 u ꢁD25 cm, UV 254 nm, n-hex-
ane/ethanol = 97:3, 0.5 mL/min), tR = 42.8 min; 1H NMR and 31P
NMR data were identical to those of ( )-2c.
To a mixture of [Pd(
aminophosphine ligand 2 (0.008 mmol), and LiOAc (0.004 mmol,
0.26 mg) in solvent (0.4 mL) were added BSA (0.6 mmol,
g
3-C3H5)Cl]2 (0.004 mmol, 1.46 mg), chiral
a
4.11. Resolution of ( )-3
0.15 mL) and racemic allylic ester 7 (0.2 mmol, 0.050 mg) at room
temperature or ꢀ20 °C under an Ar atmosphere. After 30 min, mal-
onate 8 (0.6 mmol) was added at the desired temperature. After 24
or 48 h, the reaction mixture was diluted with diethyl ether and
water. The organic layer was washed with brine and dried over
MgSO4. The filtrate was concentrated with a rotary evaporator
and the residue was purified by column chromatography.
HPLC resolution of ( )-3 (20.8 mg) dissolved in ethanol (4.0 mL)
was carried out by successive injections of 0.5 mL on a CHIRALCELÒ
OJ (1.0 u ꢁ 25 cm). A mixture of n-hexane/ethanol = 90:10 was used
as the eluent working at a flow rate of 1.5 mL/min and with UV mon-
itoring at 254 nm. Enantiomerically pure (+)-3 (6.7 mg) and (ꢀ)-3
(6.4 mg) were, respectively, obtained by evaporation of fractions.
Compound (+)-3: >99% ee; ½a D25
ꢃ
¼ þ2:6 (c 0.96, CHCl3); HPLC
4.15.1. (R)-Methyl 2-carbomethoxy-3,5-diphenylpent-4-
enonate (R)-9a15c (Table 1, entry 9)
(Daicel CHIRALCELÒ OJ (0.46 u ꢁ 25 cm, UV 254 nm, n-hexane/eth-
anol = 90:10, 0.5 mL/min), tR = 15.1 min; 1H NMR and 31P NMR
data were identical to those of ( )-2c.
46%; 99.0% ee; ½a D20
¼ þ19:2 (c 0.50, CHCl3); HPLC (Daicel CHI-
ꢃ
RALCELÒ OD-H (0.46 u ꢁ 25 cm, UV 254 nm, n-hexane/2-propa-
nol = 99:1, 0.13 mL/min), tR = 66.1 (major) and 71.4 min (minor);
1H NMR (CDCl3) d 3.51 (s, 3H), 3.70 (s, 3H), 3.96 (d, J = 10.9 Hz,
1H), 4.27 (dd, J = 8.4 and 10.9 Hz, 1H), 6.33 (dd, J = 8.4 and
15.8 Hz, 1H), 6.48 (d, J = 15.8 Hz, 1H), 7.19–7.32 (m, 10H); 13C
NMR (CDCl3) d 49.2, 52.4, 52.6, 57.6, 126.3, 127.1, 127.5, 127.8,
128.4, 128.7, 129.1, 131.8, 136.8, 140.1, 167.7, 168.2.
Compound (ꢀ)-3: >99% ee; ½a D25
¼ ꢀ2:5 (c 1.00, CHCl3); HPLC
ꢃ
(Daicel CHIRALCELÒ OJ (0.46 u ꢁ 25 cm, UV 254 nm, n-hexane/eth-
anol = 90:10, 0.5 mL/min), tR = 34.9 min; 1H NMR and 31P NMR
data were identical to those of ( )-3.
4.12. Elucidation of the thermal racemization of optically active
2a–c and 3
4.15.2. (R)-Ethyl 2-carboethoxy-3,5-diphenylpent-4-enonate
(R)-9b15c (Table 1, entry 10)
A small amount of optically active 2 or 3 was dissolved in non-
ane at room temperature. The solution was kept a constant tem-
perature in the thermostat oil bath, a small portion was taken
out several times, and the transitions of enantiomeric excess were
measured by chiral HPLC analysis.
99%; 99.0% ee; ½a D20
¼ þ16:4 (c 0.50, CHCl3); HPLC (Daicel CHI-
ꢃ
RALCELÒ OD-H (0.46 u ꢁ 25 cm, UV 254 nm, n-hexane/2-propa-
nol = 95:5, 0.7 mL/min), tR = 16.9 (major) and 21.5 min (minor);
1H NMR (CDCl3) d 1.00 (t, J = 7.1 Hz, 3H), 1.20 (t, J = 7.1 Hz, 3H),
3.90–4.00 (m, 3H), 4.17 (q, J = 7.2 Hz, 2H), 4.26 (dd, J = 8.4 and
11.0 Hz, 1H), 6.33 (dd, J = 8.4 and 15.8 Hz, 1H), 6.48 (d,
J = 15.8 Hz, 1H), 7.18–7.31 (m, 10H); 13C NMR (CDCl3) d 13.7,
14.1, 49.2, 57.7, 61.3, 61.5, 126.3, 127.0, 127.5, 127.9, 128.4,
128.6, 129.3, 131.6, 136.8, 140.2, 167.4, 167.8.
4.13. Preparation of (aR)-5c
To a mixture of (aR)-1c (0.107 g, 0.24 mmol, >99% ee) and m-xy-
lene (1.0 mL) was added DDQ (0.109 g, 0.48 mmol) and then

718
T. Mino et al. / Tetrahedron: Asymmetry 21 (2010) 711–718
2. Rosini, C.; Eranzini, L.; Raffaelli, A.; Salvadori, P. Synthesis 1992, 503.
4.16. Preparation of palladium complex 10
3. Takaya, H.; Mashima, K.; Koyano, K.; Yagi, M.; Kumobayashi, H.; Taketomi, T.;
Akutagawa, S.; Noyori, R. J. Org. Chem. 1986, 51, 629.
4. Noyori, R. Asymmetric Catalysis in Organic Synthesis; John Wiley & Sons: New
York, 1994. Chapter 1.
To a solution of racemic phosphine ( )-2a (20.4 mg, 0.05 mmol)
in chloroform (2 mL) was added [Pd(g
3-C3H5)Cl]2 (0.025 mmol,
5. Dai, W.-M.; Yeung, K. K. Y.; Liu, J.-T.; Zhang, Y.; Williams, I. D. Org. Lett. 2002, 4,
1615.
6. Chen, Y.; Smith, M. D.; Shimizu, K. D. Tetrahedron Lett. 2001, 42, 7185.
7. (a) Dai, X.; Virgil, S. Tetrahedron Lett. 1999, 40, 1245; (b) Dai, X.; Wong, A.;
Virgil, S. C. J. Org. Chem. 1998, 63, 2597.
8. (a) Kamikawa, K.; Kinoshita, S.; Furusyo, M.; Takemoto, S.; Matsuzaka, H.;
Uemura, M. J. Org. Chem. 2007, 72, 3394; (b) Kamikawa, K.; Kinoshita, S.;
Matsuzaka, H.; Uemura, M. Org. Lett. 2006, 8, 1097.
9.0 mg) at room temperature. After stirred for 20 min, chloroform
(1.3 mL) and hexane (4.0 mL) were added to the solution of palla-
dium complex. After 27 h, the crystals were filtered: 71% as a yel-
low solid; mp 153–155 °C (dec); 0.025 g, 0.036 mmol, 1H NMR
(CDCl3) d 1.69–2.28 (br m, 1H), 2.90–3.50 (br m, 1H), 3.57 (s,
3H), 4.20–5.25 (br m, 2H), 6.36 (d, J = 1.6 Hz, 1H), 6.81 (dt, J = 0.7
and 8.5 Hz, 1H), 6.84–7.20 (br m, 3H), 7.00 (t, J = 7.2 Hz, 1H), 7.14
(d, J = 8.2 Hz, 1H), 6.77–6.81 (m, 2H), 6.98–7.38 (m, 14H), 7.21–
7.65 (m, 13H); 13C NMR (CDCl3) d 56.0, 57.5 and 59.3, 79.6 and
79.9, 102.5, 113.2 (d, JCP = 35.0 Hz), 114.4 (d, JCP = 1.7 Hz), 116.9,
119.7, 119.9, 121.6, 125.8 (d, JCP = 2.3 Hz), 127.8, 128.3 (d,
JCP = 10.5 Hz), 128.5 (d, JCP = 10.4 Hz), 129.6 (d, JCP = 8.3 Hz),
130.4 ꢁ 2, 130.8 (d, JCP = 12.2 Hz), 131.2, 133.4, 133.8 (d,
JCP = 12.8 Hz), 135.1 (d, JCP = 13.0 Hz), 138.2, 157.8 (d, JCP = 8.3 Hz);
31P NMR (CDCl3) d 18.3 and 17.7; FAB-MS m/z (relative intensity):
554 (M+ꢀCl, 78); HRMS (FAB-MS) m/z calcd for C30H27ClNOPPd-Cl
554.0865, found 554.0914; X-ray diffraction analysis data of 10.
Yellow prismatic crystals from n-hexane–chloroform, triclinic
9. (a) Vorkapic-Furac, J.; Mintas, M.; Kastner, F.; Mannschreck, A. J. Heterocycl.
Chem. 1992, 29, 327; (b) Adams, R.; Joyce, R. M., Jr. J. Am. Chem. Soc. 1938, 60,
1491; (c) Bock, L. H.; Adams, R. J. Am. Chem. Soc. 1931, 53, 374.
10. (a) Mino, T.; Wakui, K.; Oishi, S.; Hattori, Y.; Sakamoto, M.; Fujita, T.
Tetrahedron: Asymmetry 2008, 19, 2711; (b) Mino, T.; Tanaka, Y.; Hattori, Y.;
Yabusaki, T.; Saotome, H.; Sakamoto, M.; Fujita, T. J. Org. Chem. 2006, 71, 7346;
(c) Mino, T.; Tanaka, Y.; Hattori, Y.; Tanaka, M.; Sakamoto, M.; Fujita, T. Lett.
Org. Chem. 2004, 1, 67; (d) Mino, T.; Tanaka, Y.; Yabusaki, T.; Okumura, D.;
Sakamoto, M.; Fujita, T. Tetrahedron: Asymmetry 2003, 14, 2503.
11. Mino, T.; Harada, Y.; Shindo, H.; Sakamoto, M.; Fujita, T. Synlett 2008, 614.
12. (a) Cooke, A. S.; Harris, M. M. J. Chem. Soc. C 1967, 988; (b) Cagle, F. W., Jr.;
Eyring, H. J. Am. Chem. Soc. 1951, 73, 5628; (c) Eyring, H. Chem. Rev. 1935, 17, 65.
13. (a) Trost, B. M. Chem. Pharm. Bull. 2002, 50, 1; (b) Trost, B. M.; Lee, C. In Catalytic
Asymmetric Synthesis; Ojima, I., Ed., 2nd ed.; VCH Publishers: New York, 2000; p
893; (c) Helmchen, G. J. Organomet. Chem. 1999, 576, 203; (d) Pfaltz, A.;
Lautens, M.. In Comprehensive Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A.,
Yamamoto, H., Eds.; Springer: Tokyo, 1999; Vol. 2, p 833. and references cited
therein.
ꢀ
space group P1, a = 9.7238(6) Å, b = 12.4329(8) Å, c = 13.7988(9)
Å,
a
= 104.8890(10)°, b = 100.6320(10)°,
c
= 102.5920(10)°, V =
14. (a) Mino, T.; Shiotsuki, M.; Yamamoto, N.; Suenaga, T.; Sakamoto, M.; Fujita, T.;
Yamashita, M. J. Org. Chem. 2001, 66, 1795; (b) Mino, T.; Imiya, W.; Yamashita,
M. Synlett 1997, 583.
1521.40(17) Å3, Z = 2,
q
= 1.549 Mg/m3,
l
(Mo K
a
) = 1.040 mmꢀ1
.
The structure was solved by the direct method of full-matrix
least-squares, where the final R and Rw were 0.0625 and 0.1692
for 6621 reflections, respectively.
15. (a) Mino, T.; Sato, Y.; Saito, A.; Tanaka, Y.; Saotome, H.; Sakamoto, M.; Fujita, T.
J. Org. Chem. 2005, 70, 7979; (b) Mino, T.; Saito, A.; Tanaka, Y.; Hasegawa, S.;
Sato, Y.; Sakamoto, M.; Fujita, T. J. Org. Chem. 2005, 70, 1937; (c) Tanaka, Y.;
Mino, T.; Akita, K.; Sakamoto, M.; Fujita, T. J. Org. Chem. 2004, 69, 6679; (d)
Mino, T.; Tanaka, Y.; Akita, K.; Sakamoto, M.; Fujita, T. Heterocycles 2003, 60, 9;
(e) Mino, T.; Tanaka, Y.; Sakamoto, M.; Fujita, T. Tetrahedron: Asymmetry 2001,
12, 2435; (f) Mino, T.; Tanaka, Y.; Akita, K.; Anada, K.; Sakamoto, M.; Fujita, T.
Tetrahedron: Asymmetry 2001, 12, 1677; (g) Mino, T.; Tanaka, Y.; Sakamoto, M.;
Fujita, T. Heterocycles 2000, 53, 1485.
References
1. (a) Bessel, C. A.; Aggarwal, P.; Marschilok, A. C.; Takeuchi, K. J. Chem. Rev. 2001,
101, 997; (b) Lagasse, F.; Kagan, H. B. Chem. Pharm. Bull. 2000, 48, 315; (c)
Buono, G.; Chiodi, O.; Wills, M. Synlett 1999, 377.