Synthesis and optical resolution of aminophosphines with axially chiral C(aryl)-N(amine) bonds for use as ligands in asymmetric catalysis

Article abstract of DOI:10.1021/jo061261f

N-Aryl indoline-type aminophosphines 1a-c were obtained in good yields by a nucleophilic aromatic substitution (S_NAr) reaction followed by silane reduction. Aminophosphine 1d was also prepared from 2,3- difluorobenzaldehyde (4) via dimethylhydr

Full text of DOI:10.1021/jo061261f

Synthesis and Optical Resolution of Aminophosphines with Axially
Chiral C(aryl)-N(amine) Bonds for Use as Ligands in
Asymmetric Catalysis
Takashi Mino,* Youichi Tanaka, Youtaro Hattori, Toshihiro Yabusaki, Hiroaki Saotome,
Masami Sakamoto, and Tsutomu Fujita
Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Chiba UniVersity, 1-33,
Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
tmino@faculty.chiba-u.jp
ReceiVed June 19, 2006
N-Aryl indoline-type aminophosphines 1a-c were obtained in good yields by a nucleophilic aromatic
substitution (SNAr) reaction followed by silane reduction. Aminophosphine 1d was also prepared from
2,3-difluorobenzaldehyde (4) via dimethylhydrazone. Optical resolution of C(aryl)-N(amine) bond
atropisomers was achieved using (S)-(+)-di-µ-chlorobis[2-[(dimethylamino)ethyl]phenyl-C2,N]dipalladium-
(II) ((S)-10). The determination of absolute configuration and the investigation of the rotation barrier for
C(aryl)-N(amine) bond axial stability of an aminophosphine 1 are described. Finally, the ability of the
chiral phosphine ligand 1 is demonstrated in a catalytic asymmetric reaction, such as a palladium-catalyzed
asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate (up to 95% ee).
Introduction
found to be useful in catalytic asymmetric reactions,6 and
C(aryl)-C(aryl) bond atropisomeric aminophosphine ligands,
such as QUINAP7 and MAP,8 were applied to transition-metal-
catalyzed asymmetric reactions during the past decades. How-
ever, the synthesis of new axially chiral biaryls is still one of
the challenges due to difficulties in forming central sterically
hindered C(aryl)-C(aryl) bonds.9 In the case of nonbiaryl C-C
Chiral phosphines are important molecules that effect asym-
metric inductions as ligands for transition metal catalysts.1,2
Atropisomeric biaryls3 are also well established as one important
class of ligands for asymmetric metal-catalyzed reactions by
the discovery and application of BINAP.4 It is suggested that
this ligand’s chiral environment and the chelating nature are
imposed with two orthogonal naphthalene rings that induce high
stereoselectivity in various asymmetric reactions.5 Binaphthyl-
monophosphines (MOPs) and related ligands have also been
(6) (a) Hayashi, T.; Iwamura, H.; Uozumi, Y.; Matsumoto, Y.; Ozawa,
F. Synthesis 1994, 15, 526. (b) Uozumi, Y.; Tanahashi, A.; Lee, S.-Y.;
Hayashi, T. J. Org. Chem. 1993, 58, 1945.
(7) (a) Brown, J. M.; Hulmes, D. I.; Guiry, P. J. Tetrahedron 1994, 50,
4493. (b) Brown, J. M.; Hulmes, D. I.; Layzell, T. P. J. Chem. Soc., Chem.
Commun. 1993, 22, 1673. (c) Alcock, N. W.; Brown, J. M.; Hulmes, D. I.
Tetrahedron: Asymmetry 1993, 4, 743.
(8) (a) Ding, K.; Wang, Y.; Yun, H.; Liu, J.; Wu, Y.; Terada, M.; Okubo,
Y.; Mikami, K. Chem.sEur. J. 1999, 5, 1734. (b) Vyskocil, S.; Smrcina,
M.; Kocovsky, P. Tetrahedron Lett. 1998, 39, 9289. (c) Vyskocil, S.;
Smrcina, M.; Hanus, V.; Polasek, M.; Kocovsky, P. J. Org. Chem. 1998,
63, 7738.
(1) Yamanoi, Y.; Imamoto, T. ReV. Heteroatom Chem. 1999, 20, 227.
(2) Buono, G.; Chiodi, O.; Wills, M. Synlett 1999, 377.
(3) Rosini, C.; Eranzini, L.; Raffaelli, A.; Salvadori, P. Synthesis 1992,
503.
(4) Takaya, H.; Mashima, K.; Koyano, K.; Yagi, M.; Kumobayashi, H.;
Taketomi, T.; Akutagawa, S.; Noyori, R. J. Org. Chem. 1986, 51, 629.
(5) Noyori, R. Asymmetric Catalysis in Organic Synthesis; John Wiley
& Sons: New York, 1994; Chapter 1.
10.1021/jo061261f CCC: $33.50 © 2006 American Chemical Society
Published on Web 08/23/2006
7346
J. Org. Chem. 2006, 71, 7346-7353

Aminophosphines with Chiral C(aryl)-N(amine) Bonds
SCHEME 1. Preparation of Aminophosphine Ligands 1a-c
bond atropisomeric ligands, C(aryl)-C(amide carbonyl) bond
atropisomeric phosphine ligands10 and C(aryl)-N(non-amine)
bond atropisomeric phosphine ligands, such as quinazolinone-
containing N-anilide-type ligand11 and N-arylimide-type ligand,12
have been reported. Although the synthesis of C(aryl)-N(amine)
bond atropisomeric N-aryl indoles by stereoselective SNAr
reaction of a planar chiral arene Cr complex was recently
reported by Kamikawa,13 even the discovery of C(aryl)-
N(amine) bond atropisomeric compounds has been rarely
described.14 The use of the ligand for catalytic asymmetric
reaction has hardly been discovered. Previously, we prepared
those compounds using an approach similar to the synthesis of
pyrrolidinyl-containing aminophosphines.15 We herein report the
synthesis of a C(aryl)-N(amine) bond atropisomeric N-aryl
indoline-type aminophosphine 1, the facile optical resolution
by the separation of diastereomeric palladium complex mixtures,
and applications to the palladium-catalyzed asymmetric allylic
alkylation.16
SCHEME 2. Preparation of Aminophosphine Ligand 1d
Results and Discussion
Preparation of N-Aryl Indoline-type Aminophosphine 1.
Aminophosphine ligands 1a-c were easily prepared in two
steps. A nucleophilic aromatic substitution (SNAr) reaction of
the corresponding phosphine oxides, such as 1-methoxy-2-
(diphenylphosphino)naphthalene oxide (2a), with lithium salt
of indoline gave the corresponding aminophosphine oxide 3a.
This aminophosphine oxide was converted into the desired
aminophosphine ligand 1a using trichlorosilane triethylamine
in good yield (Scheme 1). Aminophosphines 1b and 1c were
easily prepared in the same manner.
N-Aryl indoline-type aminophosphine 1d was prepared in six
steps from 2,3-difluorobenzaldehyde (4).17 Dimethylhydrazone
5 was easily prepared from the corresponding aldehyde 4 and
N,N-dimethylhydrazine (DMH) as a protecting reagent with
trifluoroacetic acid (TFA) as a catalyst in ether (Scheme 1).
We examined the nucleophilic aromatic substitution (SNAr)
reaction of (E)-1-(2,3-difluorobenzaldehyde)-N,N-dimethylhy-
drazone (5) with lithiated indoline; as a result, dimethylhydra-
zone 5 was converted into the desired N-aryl indoline derivative
6 in a 96% yield, indicating that the hydrazone subunit of the
2-fluorine was activated as a leaving group. The next step is
the introduction of a phosphine substituent, and we successfully
prepared aminophosphine hydrazone 7 by nucleophilic phos-
phanilation with potassium diphenylphosphide in a 97% yield.
The corresponding aldehyde 8 was obtained by hydrolysis of 7
using 6 M hydrochloric acid, and the reduction of aldehyde 8
with sodium borohydride gave the corresponding alcohol 9 in
a 92% yield. Finally, this alcohol was converted into amino-
phosphine 1d using acetic anhydride-triethylamine-DMAP in
good yield.
Investigations of the Existence of the Axial Chirality of
1. We successfully conducted single-crystal X-ray diffraction
analysis of N-aryl indoline-type aminophosphines 1a-d and its
precursor aminophosphine 9, and their ORTEP diagrams are
shown in Figures S1-S5 (see Supporting Information). The
C(aryl)-N(amine) bonds are twisted between an aryl ring with
a diphenylphosphino group and an indoline ring. To investigate
whether C(aryl)-N(amine) bond axial chirality exists in ami-
nophosphines 1a-d, we analytically separated these isomers
by using HPLC on a chiral phase. As a result, we obtained
almost resolved UV plots for aminophosphines 1a-d in addition
(9) (a) Stanforth, S. Tetrahedron 1998, 54, 263. (b) Bringmann, G.;
Walter, R.; Weirich, R. Angew. Chem., Int. Ed. Engl. 1990, 29, 977.
(10) Dai, W.-M.; Yeung, K. K. Y.; Liu, J.-T.; Zhang, Y.; Williams, I.
D. Org. Lett. 2002, 4, 1615.
(11) Chen, Y.; Smith, M. D.; Shimizu, K. D. Tetrahedron Lett. 2001,
42, 7185.
(12) (a) Dai, X.; Virgil, S. Tetrahedron Lett. 1999, 40, 1245. (b) Dai,
X.; Wong, A.; Virgil, S. C. J. Org. Chem. 1998, 63, 2597.
(13) Kamikawa, K.; Kinoshita, S.; Matsuzaka, H.; Uemura, M. Org. Lett.
2006, 8, 1097.
(14) (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.
(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) Kondo, K.;
Kazuta, K.; Fujita, H.; Sakamoto, Y.; Murakami, Y. Tetrahedron 2002,
58, 5209. (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. Tetrahedron: Asymmetry 2001, 12, 2435. (h)
Mino, T.; Tanaka, Y.; Sakamoto, M.; Fujita, T. Heterocycles 2000, 53, 1485.
(16) Preliminary communication: Mino, T.; Tanaka, Y.; Yabusaki, T.;
Okumura, D.; Sakamoto, M.; Fujita, T. Tetrahedron: Asymmetry 2003, 14,
2503.
(17) Preliminary communication: Mino, T.; Tanaka, Y.; Hattori, Y.;
Tanaka, M.; Sakamoto, M.; Fujita, T. Lett. Org. Chem. 2004, 1, 67.
J. Org. Chem, Vol. 71, No. 19, 2006 7347

Mino et al.
SCHEME 3. Optical Resolution Procedure of C(aryl)-
N(amine) Bond Atropisomeric Aminophosphine (()-1
FIGURE 1. Chiral phase HPLC UV and CD charts of (()-1. (A) (()-
1a: Daicel CHIRALCEL OJ (0.46 φ × 25 cm, hexane:ethanol ) 90:
10, 0.50 mL/min). (B) (()-1b: Daicel CHIRALPAK AD-H × 2 (0.46
φ × 25 cm × 2, hexane:ethanol ) 99.7:0.3, 0.25 mL/min). (C) (()-
1c: Daicel CHIRALPAK AD-H × 2 (0.46 φ × 25 cm × 2, hexane:
ethanol ) 99.7:0.3, 0.25 mL/min). (D) (()-1d: Daicel CHIRALCEL
OD + OD-H (0.46 φ × 25 cm × 2, hexane:ethanol ) 99:1, 0.50 mL/
min).
to a pair of clear positive (+) and negative (-) CD trace signals
of HPLC run at 254 nm (Figure 1). This result indicated the
existence of a pair of atropisomers in N-aryl indoline-type
aminophosphines 1a-d.
Optical Resolution and Determination of Absolute Con-
figuration of 1. We next attempted the optical resolution of
aminophosphines (()-1 into each C(aryl)-N(amine) bond
atropisomer that used (S)-(+)-di-µ-chlorobis[2-[(dimethyl-
amino)ethyl]phenyl-C2,N]dipalladium(II) ((S)-10)18 as a chiral
resolving agent. We used a simple separation using a silica gel
column chromatography procedure. Racemic N-aryl indoline-
type aminophosphines (()-1 were resolved by coordination with
a chiral palladium complex, such as (S)-10, in toluene at room
temperature (Scheme 3). The resulting diastereomeric palladium
complex mixture of (aS,S)-11 and (aR,S)-12 was kinetically
stable, and a large difference in the polarity of the diastereomers
was observed by using an ether eluent on TLC. In fact,
diastereoisomers (aS,S)-11 and (aR,S)-12 were easily separable
by silica gel column chromatography. The individual diaster-
eomers of (aS,S)-11 and (aR,S)-12 were treated with ethylene-
diamine (EDA) to release the enantiomerically pure (aS)-1 or
(aR)-1. The optical purity of divided (aS)-1 and (aR)-1 was more
than 99% ee from chiral HPLC analyses.
Stability of the C-N Bond Axial Chirality of 1. We
conducted a study on the thermal racemization of atropisomeric
aminophosphines 1. We assessed the rate of racemization by
following first-order decay in enantiomeric excess in time at a
suitable temperature. A small portion of the solution of optically
active 1 in toluene was taken out at regular intervals and
subsequently analyzed for enantiomeric excesses by chiral
HPLC analysis. We repeated the experiment at three tempera-
tures and determined the rate constant (krac) of 1 at each
temperature (Figures S10-S13; see Supporting Information).
For example, the rotational barrier (∆Gqrac) of 1c was found to
be 27.9 kcal/mol in toluene at 25 °C according to the Arrhenius
and the Eyring equation.20 This result corresponds to a half-
life of approximately 1.7 × 102 days.
X-ray Structure of Palladium Complex (()-13. Ligand (()-
1b was treated with PdCl2(MeCN)2 to give the palladium
complex (()-13, and its suitable crystal was obtained from
hexane-CHCl3. X-ray analysis of (()-13 was carried out
(Figure 2). The solid-state structure shows that ligand 1b is
coordinated to palladium with a five-membered chelate ring via
a phosphorus and nitrogen group of 1b, which is bonded to
palladium. The trans influence of the P,N-ligand is reflected in
the lengthening of the Pd-Cl bond in trans disposition to the
Determination of the absolute configurations of 1 was decided
by single-crystal X-ray analysis of palladium complexes 11 or
12 (Figure S6-S9; see Supporting Information). On the basis
of the known S-stereochemistry of the phenethylamine moiety,
the absolute configuration of the C(aryl)-N(amine) bond chiral
axis is assigned according to the Cahn-Ingold-Prelog rule.19
(18) (a) Roberts, N. K.; Wild, S. B. J. Am. Chem. Soc. 1979, 101, 6254.
(b) Roberts, N. K.; Wild, S. B. J. Chem. Soc., Dalton Trans. 1979, 2015.
(c) Tani, K.; Brown, L. D.; Ahmed, J.; Ibers, J. A.; Yokota, M.; Otsuka, S.
J. Am. Chem. Soc. 1977, 99, 7876. (d) Otsuka, S.; Nakamura, A.; Kano,
T.; Tani, K. J. Am. Chem. Soc. 1971, 93, 4301.
(19) Eliel, E. L.; Wilen, S. H.; Mander, L. N. Stereochemistry of Organic
Compounds; John Wiley & Sons: New York, 1994.
(20) (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, 35, 65.
7348 J. Org. Chem., Vol. 71, No. 19, 2006

Aminophosphines with Chiral C(aryl)-N(amine) Bonds
1-4). When the reaction was carried out using (aS)-1d as a
ligand, the enantioselectivity of product (R)-16 was obtained
higher than the case of chiral 1a-c with good yield (entry 4 vs
entries 1-3). We examined the effect of reaction solvents using
the chiral ligand (aS)-1d. When the reaction was carried out in
ether instead of PhMe, (R)-16 was obtained with a similar level
of enantioselectivity (entry 4 vs entry 5). By use of THF, the
enantioselectivity and yield were slightly decreased (entry 6).
We also investigated the effect of reaction temperature. The
reaction under 0 °C proceeded slowly with 89% ee (entry 7).
Conclusion
FIGURE 2. ORTEP drawing of palladium complex (()-13. Two
molecules of chloroform are omitted for clarity. Selected bond lengths
(Å) and angles (deg): Pd-P, 2.193(2); Pd-N, 2.128(5); Pd-Cl(1),
2.392(2); Pd-Cl(2), 2.303(2); Cl(1)-Pd-Cl(2), 91.31(6); Cl(1)-Pd-
P, 178.08(7); Cl(1)-Pd-N, 94.1(1); Cl(2)-Pd-P, 87.64(6); Cl(2)-
Pd-N, 174.4(2); P-Pd-N, 86.9(1).
N-Aryl indoline-type C(aryl)-N(amine) bond axially chiral
aminophosphines 1 were prepared, and the resolution of these
isomers was achieved by using chiral palladium dimer complex
(S)-10 as a resolving agent. Finally, the ability of the chiral
phosphine ligand 1 is demonstrated in a catalytic asymmetric
reaction, such as a palladium-catalyzed asymmetric allylic
alkylation, of 1,3-diphenyl-2-propenyl acetate with high enan-
tioselectivity.
TABLE 1. Palladium-Catalyzed Asymmetric Allylic Alkylation
Using 1a
Experimental Section
1-Methoxy-2-diphenylphosphinonaphthalene oxide (2a)23 and
2-methoxy-3-methylphenyldiphenylphosphine oxide (2b)15g were
prepared according to the literature method.
Preparation of 2-Methoxy-3-trifluoromethylphenyldiphe-
nylphosphine Oxide (2c): To a mixture of 2-trifluoromethylanisole
(1.761 g, 10.0 mmol), TMEDA (1.51 mL, 10.0 mmol), and ether
(25 mL) was added dropwise n-BuLi in hexane (9.2 mL, 14.7 mmol,
1.66 M) over 10 min. The mixture was stirred at room temperature
for 2 h then treated with chlorodiphenylphosphine (1.8 mL, 10.0
mmol), and the resulting mixture was diluted with ether and
quenched with 2 M aqueous HCl. The organic layer was washed
with 2 M aqueous Na2CO3, brine, dried over MgSO4, and
concentrated under reduced pressure. The residue was dissolved
in AcOH (50 mL) and treated with 30% aqueous H2O2 (1.5 mL)
then gradually heated to 80 °C for 2 h. The mixture was cooled to
room temperature and diluted with ether (100 mL) then treated with
2 M aqueous NaOH at 0 °C. The water layer was extracted with
ether, and the combined extracts were washed with water, dried
over MgSO4, and concentrated under reduced pressure. The residue
was purified by silica gel chromatography (elution with n-hexane:
entry ligand solvent temp time (h) yield (%)b ee (%) (config)c
1
2
3
4
5
6
7
(aS)-1a
PhMe rt
24
24
24
24
24
24
24
88
89
93
91
89
70
27
89 (R)
90 (S)
93 (S)
95 (R)
94 (R)
91 (R)
89 (R)
(aR)-1b PhMe rt
(aR)-1c PhMe rt
(aS)-1d PhMe rt
(aS)-1d Et2O
(aS)-1d THF
rt
rt
(aS)-1d PhMe 0 °C
a The reactions were carried out on 0.2 mmol scale in various solvents
(0.4 mL) at various temperatures with 3.0 equiv of 15 and BSA, in the
presence of LiOAc (5 mol %) and ligand 1 (10 mol %) and [Pd(η3-C3H5)Cl]2
(5 mol %). b Isolated yields. c Determined by HPLC analysis using a chiral
column (Daicel CHIRALCEL OD-H).
1
EtOAc ) 1:3): 87%; mp 105-106 °C; H NMR (CDCl3) δ 3.65
(s, 3H), 7.26 (dt, J ) 1.1 and 7.8 Hz, 1H), 7.44-7.60 (m, 7H),
7.68-7.82 (m, 5H); 13C NMR (CDCl3) δ 64.8 (d, JCP ) 2.4 Hz),
123.7 (dq, JCP and JCF ) 2.4 and 273.3 Hz), 124.2 (d, JCP ) 12.2
phosphorus to the Pd-Cl distance trans to the nitrogen [2.392-
(2) vs 2.303(2) Å].
Palladium-Catalyzed Asymmetric Allylic Alkylation. Fi-
nally, we investigated the ability of chiral aminophosphines 1
as chiral ligands for the palladium-catalyzed asymmetric allylic
alkylation21 using 1,3-diphenyl-2-propenyl acetate (14) with
dimethyl malonate (15). This reaction was carried out in the
presence of 5 mol % of [Pd(η3-C3H5)Cl]2, 10 mol % of 1, and
a mixture of N,O-bis(trimethylsilyl)acetamide (BSA) and 5 mol
% of LiOAc22 (Table 1). The chiral ligands 1 are able to induce
good enantioselectivities in toluene at room temperature (entries
Hz), 125.5 (dq, JCP and JCF ) 7.3 and 31.2 Hz), 129.0 (d, JCP
)
12.4 Hz), 130.1 (d, JCP ) 101.2 Hz), 132.1 (d, JCP ) 10.0 Hz),
132.5 (dq, JCP and JCF ) 2.0 and 5.1 Hz), 132.9 (d, JCP ) 10.8
Hz), 139.0 (d, JCP ) 8.9 Hz), 161.7 (q, JCF ) 1.7 Hz); 31P NMR
(CDCl3) δ 27.0; EI-MS m/z (relative intensity) 376 (M+, 47); HRMS
(FAB-MS) m/z calcd for C20H16O2PF3 + H 377.0918, found
377.0922.
Typical Procedure for the Preparation of Aminophosphine
Oxide 3. To the solution of indoline (0.104 g, 1.03 mmol) in THF
(1 mL) was added slowly n-BuLi in hexane (0.71 mL, 1.1 mmol,
1.56 M) at -80 °C for 10 min, and then at room temperature for
2 h. After phosphine oxide (1.0 mmol) was added at 0 °C, stirring
was continued for 20 h at room temperature. The mixture was
diluted with ether and quenched with saturated aqueous NH4Cl.
The organic layer was washed with brine, dried over MgSO4, and
(21) (a) Trost, B. M. Chem. Pharm. Bull. 2002, 50, 1. (b) Trost, B. M.;
Lee, C. In Catalytic Asymmetric Synthesis, 2nd ed.; ed. by Ojima, I., 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 therein.
(22) (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.
(23) Hattori, T.; Sakamoto, J.; Hayashizaka, N.; Miyano, S. Synthesis
1994, 199.
J. Org. Chem, Vol. 71, No. 19, 2006 7349

Mino et al.
concentrated under reduced pressure. The residue was purified by
silica gel chromatography.
) 87.76(3)°, V ) 1180.3(7) Å3, Z ) 2, F ) 1.209 g/cm3, µ (Cu
KR) ) 11.5 cm-1. The structure was solved by the direct method
of full-matrix least-squares, where the final R and Rw were 0.057
and 0.128 for 2585 reflections, respectively.
1-[2′-(Diphenylphosphinyl)-1′-naphthalenyl]-2,3-dihydro-1H-
1
indole (3a): 83%; mp 138 °C; H NMR (CDCl3) δ 2.95-3.01
(m, 2H), 3.80-3.87 (m, 1H), 4.34 (dt, J ) 2.5 and 6.8 Hz, 1H),
5.42 (d, J ) 5.5 Hz, 1H), 6.48-6.54 (m, 2H), 6.93 (d, J ) 5.3 Hz,
1H), 7.14-7.33 (m, 4H), 7.43-7.67 (m, 8H), 7.83-7.93 (m, 4H);
13C NMR (CDCl3) δ 28.7, 56.3, 108.3, 117.4, 123.9, 124.8, 126.2,
126.5, 127.5-128.0 (m), 128.3-129.1 (m), 130.4-130.7 (m),
131.3, 132.0-132.7 (m), 133.3 (d, JCP ) 24.9 Hz), 133.7, 137.4,
145.6, 150.8; 31P NMR (CDCl3) δ 25.8; FAB-MS m/z (relative
intensity): 446 (M+ + 1, 100), 445 (M+, 90); HRMS (FAB-MS)
m/z calcd for C30H24NOP 445.1596, found 445.1565.
(()-1-[2′-(Diphenylphospino)-6′-methylphenyl]-2,3-dihydro-
1
1H-indole ((()-1b): 88%; mp 193 °C; H NMR (CDCl3) δ 1.95
(s, 3H), 2.92-2.98 (m, 2H), 3.50 (t, J ) 8.7 Hz, 2H), 5.64 (d, J )
7.7 Hz, 1H), 6.44 (t, J ) 7.2 Hz, 1H), 6.65-6.75 (m, 2H), 6.92-
6.95 (m, 1H), 7.04-7.25 (m, 7H), 7.25-7.27 (m, 5H); 13C NMR
(CDCl3) δ 18.4 (d, JCP ) 10.0 Hz), 28.8, 52.6 (d, JCP ) 16.4 Hz),
106.4, 116.7, 124.1, 127.0, 127.5, 128.1 (t, JCP ) 24.6 Hz), 128.4
(t, JCP ) 28.0 Hz), 131.4, 132.5, 133.9 (d, JCP ) 36.4 Hz), 134.1
(d, JCP ) 36.4 Hz), 137.1 (d, JCP ) 10.0 Hz), 137.2, 137.8 (d, JCP
) 13.2 Hz), 138.0 (d, JCP ) 6.8 Hz), 141.5 (dd, JCP ) 11.4 and
21.4 Hz), 150.3; 31P NMR (CDCl3) δ -14.1; FAB-MS m/z (relative
intensity): 393 (M+, 9); HRMS (FAB-MS) m/z calcd for C27H24-
NP 393.1646, found 393.1624; HPLC Daicel CHIRALPAK AD-H
× 2 (0.46 φ × 25 cm × 2, UV 254 nm, hexane:ethanol ) 99.7:
0.3, 0.15 mL/min), tR ) 58.1 (CD, λext (∆ꢀ) 254 (-)) and 63.3
min (CD, λext (∆ꢀ) 254 (+)); X-ray diffraction analysis data of (()-
1b (Figure S2). Colorless prismatic crystals from hexanes-ethanol,
monoclinic space group P21/c, a ) 11.445(3) Å, b ) 11.105(4) Å,
c ) 14.798(8) Å, â ) 113.59(8)°, V ) 2189.3(15) Å3, Z ) 4, F )
1.194 g/cm3, µ (Cu KR) ) 11.9 cm-1. The structure was solved by
the direct method of full-matrix least-squares, where the final R
and Rw were 0.043 and 0.072 for 1783 reflections, respectively.
(()-1-[2′-(Diphenylphosphino)-6′-trifluoromethylphenyl]in-
1-[2′-(Diphenylphosphinyl)-6′-methylphenyl]-2,3-dihydro-1H-
1
indole (3b): 67%; mp 193 °C; H NMR (CDCl3) δ 1.97 (s, 3H),
2.86-2.92 (m, 2H), 3.48-3.61 (m, 1H), 4.31-4.38 (m, 1H), 5.50
(d, J ) 7.7 Hz, 1H), 6.45 (t, J ) 7.3 Hz, 1H), 6.61 (t, J ) 7.6 Hz,
1H), 6.84 (d, J ) 7.2 Hz, 1H), 7.11-7.26 (m, 5H), 7.41-7.48 (m,
4H), 7.56-7.63 (m, 2H), 7.80-7.87 (m, 2H); 13C NMR (CDCl3)
δ 18.6, 28.6, 54.6, 123.9 126.1, 126.8, 127.0, 127.9-128.5 (m),
130.3-130.4 (m), 130.5, 131.4 (d, JCP ) 11.7 Hz), 131.9, 132.2
(d, JCP ) 36.0 Hz), 132.5 (d, JCP ) 45.3 Hz), 133.5 (d, JCP ) 54.6
Hz), 135.8, 136.5 (d, JCP ) 8.4 Hz), 137.2, 139.8 (d, JCP ) 28.5
Hz), 145.0 (d, JCP ) 15.9 Hz), 149.4; 31P NMR (CDCl3) δ 26.3;
FAB-MS m/z (relative intensity): 410 (M+ + H, 100), 409 (M+,
90); HRMS (FAB-MS) m/z calcd for C27H24NOP 409.1596, found
409.1567.
1
doline ((()-1c): 86%; mp 95-96 °C; H NMR (CDCl3) δ 3.07-
1-[2′-(Diphenylphosphinyl)-6′-trifluoromethylphenyl]-2,3-di-
1
3.25 (m, 2H), 3.75-3.92 (m, 2H), 5.64 (d, J ) 7.7 Hz, 1H), 6.53
(dt, J ) 0.74 and 7.3 Hz, 1H), 6.66 (t, J ) 7.3 Hz, 1H), 7.04-7.12
(m, 3H), 7.16-7.38 (m, 10H), 7.72-7.76 (m, 1H); 13C NMR
(CDCl3) δ 29.0, 54.8 (dd, JCP ) 1.3 and 7.7 Hz), 107.1, 117.1,
123.7 (dq, JCP and JCF ) 2.2 and 273.8 Hz), 124.1, 126.8, 127.8,
128.2-128.9 (m), 132.5 (dq, JCP and JCF ) 4.7 and 30.1 Hz), 133.4
(d, JCP ) 19.6 Hz), 134.0 (d, JCP ) 21.2 Hz), 135.8 (d, JCP ) 12.7
Hz), 137.3 (d, JCP ) 12.7 Hz), 139.9, 144.1 (d, JCP ) 17.5 Hz),
146.1 (dd, JCP ) 1.4 and 24.5 Hz), 151.7 (d, JCP ) 1.9 Hz); 31P
NMR (CDCl3) δ -17.9; EI-MS m/z (relative intensity) 447 (M+,
100); HRMS (FAB-MS) m/z calcd for C26H20NF3P 447.1364, found
447.1352; HPLC Daicel CHIRALPAK AD-H × 2 (0.46 φ × 25
cm × 2, UV 254 nm, hexane:ethanol ) 99.7:0.3, 0.15 mL/min), tR
) 33.0 (CD, λext (∆ꢀ) 254 (-)) and 35.5 min (CD, λext (∆ꢀ) 254
(+)); X-ray diffraction analysis data of (()-1c (Figure S3). Colorless
prismatic crystals from hexane, triclinic space group P1h, a ) 9.550-
(2) Å, b ) 10.913(6) Å, c ) 11.511(5) Å, R ) 108.01(4)°, â )
92.35(3)°, γ ) 96.46(3)°, V ) 1130.1(8) Å3, Z ) 2, F ) 1.203
g/cm3, µ (Cu KR) ) 12.4 cm-1. The structure was solved by the
direct method of full-matrix least-squares, where the final R and
Rw were 0.053 and 0.158 for 3658 reflections, respectively.
Preparation of (E)-1-(2,3-Difluorobenzaldehyde)-N,N-dim-
ethylhydrazone (5). A mixture of 2,3-difluorobenzaldehyde (4)
(2.84 g, 20.0 mmol) and N,N-dimethylhydrazine (1,202 g, 20.0
mmol) in diethyl ether (20 mL) was stirred at room temperature
for 1 h in the presence of a catalytic amount of trifluoroacetic acid
(ca. 1 drop). The mixture was concentrated under reduced pressure,
and the residue was purified by silica gel column chromatography
(elution with n-hexane:EtOAc ) 15:1): 3.53 g, 19.1 mmol, 96%;
1H NMR (CDCl3) δ 3.03 (s, 6H), 6.94-7.01 (m, 2H), 7.30 (s, 1H),
hydro-1H-indole (3c): 65%; mp 80-82 °C; H NMR (CDCl3) δ
2.88-3.03 (m, 2H), 3.73 (q, J ) 9.3 Hz, 1H), 4.48 (dt, J ) 5.7
and 8.4 Hz, 1H), 5.39 (d, J ) 7.6 Hz, 1H), 6.39-6.51 (m, 2H),
6.81 (dd, J ) 0.8 and 7.1 Hz, 1H), 7.02-7.25 (m, 3H), 7.43-7.62
(m, 7H), 7.76-7.83 (m, 2H), 7.92 (d, J ) 7.8 Hz, 1H); 13C NMR
(CDCl3) δ 28.7, 55.9, 123.3 (dq, JCP and JCF ) 2.4 and 274.7 Hz),
123.6, 125.8, 127.4 (d, JCP ) 12.9 Hz), 128.2 (d, JCP ) 12.6 Hz),
128.5-128.6 (m), 130.4-130.6 (m), 130.9 (d, JCP ) 2.9 Hz),
131.7-131.8 (m), 132.1 (d, JCP ) 9.2 Hz), 132.4-133.2 (m), 138.7,
(d, JCP ) 11.2 Hz), 140.2 (d, JCP ) 102.5 Hz), 145.5-145.6 (m),
150.1; 31P NMR (CDCl3) δ 25.9; EI-MS m/z (relative intensity)
463 (M+, 100); HRMS (FAB-MS) m/z calcd for C27H21ONF3P
463.1313, found 463.1282.
Typical Procedure for the Preparation of Aminophosphine
1a-c. To a mixture of phosphine oxide 3 (0.3 mmol) and
triethylamine (0.34 mL, 1.2 mmol) in m-xylene (2 mL) was added
trichlorosilane (0.24 mL, 1.2 mmol) at 0 °C under an Ar atmosphere.
The reaction mixture was refluxed for 6 h. After being cooled to
room temperature, the mixture was diluted with ether and 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:EtOAc ) 6:1).
(()-1-[2′-(Diphenylphosphino)-1′-naphthalenyl]-2,3-dihydro-
1
1H-indole ((()-1a): 95%; mp 162-163 °C; H NMR (CDCl3) δ
3.11 (t, J ) 8.8 Hz, 2H), 3.63 (q, J ) 7.6 Hz, 1H), 3.78 (q, J ) 9.9
Hz, 1H), 5.90 (d, J ) 7.6 Hz, 1H), 6.49 (dt, J ) 0.7 and 7.4 Hz,
1H), 6.64 (t, J ) 7.2 Hz, 1H), 7.03-7.08 (m, 2H), 7.14-7.29 (m,
11H), 7.36-7.40 (m, 1H), 7.58 (d, J ) 8.4 Hz, 1H), 7.66 (d, J )
8.8 Hz, 1H), 7.80 (d, J ) 8.4 Hz, 1H); 13C NMR (CDCl3) δ 29.0,
54.1, 107.0, 124.0, 124.3, 126.4, 126.5, 127.2, 127.8 (d, JCP ) 10.0
Hz), 128.1, 128.2-128.8 (m), 129.9, 130.8, 133.8-134.0 (m),
135.7, 137.3, 137.4, 137.8, 137.9, 138.0, 138.1, 143.7, 144.0, 151.6;
31P NMR (CDCl3) δ -14.8; FAB-MS m/z (relative intensity): 429
(M+, 10); HRMS (FAB-MS) m/z calcd for C30H24NP 429.1601,
found 429.1623; HPLC Daicel CHIRALCEL OJ (0.46 φ × 25 cm,
UV 254 nm, hexane:ethanol ) 90:10, 0.50 mL/min), tR ) 13.0
(CD, λext (∆ꢀ) 254 (-)) and 31.3 min (CD, λext (∆ꢀ) 254 (+));
X-ray diffraction analysis data of (()-1a (Figure S1). Yellow plate
crystals from ethanol, triclinic space group P1h, a ) 9.129(4) Å, b
) 11.674(4) Å, c ) 11.962(4) Å, R ) 68.03(3)°, â ) 86.95(3)°, γ
7.57-7.62 (m, 1H); 13C NMR (CDCl3) δ 42.1, 114.2 (d, JCF
)
17.1 Hz), 119.3 (t, JCF ) 3.0 Hz), 122.2 (t, JCF ) 4.4 Hz), 123.2
(dd, JCF ) 4.6 and 7.1 Hz), 126.5 (d, JCF ) 6.8 Hz), 149.1 (d, JCF
) 12.5 Hz), 152.4 (d, JCF ) 12.5 Hz); EI-MS m/z (relative intensity)
184 (M+, 100); HRMS (FAB-MS) m/z calcd for C9H10F2N2
184.0812, found 184.0816.
Preparation of (E)-1-[3-Fluoro-2-(indolin-1-yl)benzaldehyde]-
N,N-dimethylhydrazone (6). To a solution of indoline (4.29 g,
36.0 mmol) in THF (36 mL) was added slowly n-BuLi in hexane
(23.9 mL, 37.8 mmol, 1.58 M) at -78 °C, and then stirred at the
same temperature for 10 min. After the THF solution of 5 (3.32 g,
7350 J. Org. Chem., Vol. 71, No. 19, 2006

Aminophosphines with Chiral C(aryl)-N(amine) Bonds
18.0 mmol in 18 mL) was added at -78 °C, stirring was continued
for 24 h at room temperature. The mixture was quenched with
saturated aqueous NH4Cl and diluted with 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 column chromatography (elution with n-hexane:EtOAc
13C NMR (CDCl3) δ 28.9, 54.1 (d, JCP ) 5.5 Hz), 61.4 (d, JCP
)
2.2 Hz), 106.2, 117.3, 124.5, 127.2, 128.1-128.7 (m), 130.4,
133.8-134.3 (m), 136.9 (d, JCP ) 11.7 Hz), 137.7 (d, JCP ) 12.4
Hz), 141.0 (d, JCP ) 2.7 Hz), 141.6 (d, JCP ) 10.4 Hz), 144.2 (d,
JCP ) 22.9 Hz), 151.0; 31P NMR (CDCl3) δ -15.3; EI-MS m/z
(relative intensity) 409 (M+, 100); HRMS (FAB-MS) m/z calcd
for C27H24NOP 409.1596, found 409.1602; X-ray diffraction
analysis data of 9 (Figure S5). Colorless prismatic crystals from
methanol, C27H24NOP, monoclinic space group C2/c, a ) 32.489-
(13) Å, b ) 8.345(5) Å, c ) 21.857(8) Å, â ) 132.24(3)°, V )
4387(4) Å3, Z ) 8, F ) 1.240 g/cm3, µ (Cu KR) ) 12.4 cm-1. The
structure was solved by the direct method of full-matrix least-
squares, where the final R and Rw were 0.0585 and 0.1612 for
4170 reflections, respectively.
1
) 40:1): 4.87 g, 17.2 mmol, 96%; H NMR (CDCl3) δ 2.89 (s,
6H), 3.17-3.22 (m, 2H), 3.77-3.91 (m, 2H), 6.17 (d, J ) 7.8 Hz,
1H), 6.67 (dt, J ) 0.7 and 7.4 Hz, 1H), 6.94-7.01 (m, 2H), 7.15
(d, J ) 1.0 Hz, 1H), 7.19 (dd, J ) 2.8 and 8.3 Hz, 1H), 7.35 (s,
1H), 7.75 (d, J ) 8.0 Hz, 1H); 13C NMR (CDCl3) δ 29.5, 43.1,
54.3, 107.9, 115.4 (d, JCF ) 20.0 Hz), 118.3, 120.9, 125.0, 127.7,
128.0 (d, JCF ) 8.8 Hz), 128.6-129.1 (m), 129.4, 134.1 (dd, JCF
) 17.0 and 55.0 Hz), 138.5 (d, JCF ) 3.0 Hz), 151.6, 161.0 (d, JCF
) 250.4 Hz); EI-MS m/z (relative intensity) 283 (M+, 12); HRMS
(FAB-MS) m/z calcd for C17H18FN3 283.1485, found 283.1484.
Preparation of (E)-1-[3-Diphenylphosphino-2-(indolin-1-yl)-
benzaldehyde]-N,N-dimethylhydrazone (7). To a solution of 6
(3.54 g, 12.5 mmol) in THF (5.0 mL) was added slowly potassium
diphenylphosphide in THF (50.0 mL, 25.0 mmol, 0.50 M) at room
temperature, and then stirred at 55 °C for 24 h. After cooled to
room temperature, the mixture was quenched with saturated aqueous
NH4Cl and diluted with EtOAc. The organic layer was washed with
water and brine, dried over MgSO4, and concentrated under reduced
pressure. The residue was purified by silica gel column chroma-
tography (elution with n-hexane:EtOAc ) 40:1): 5.10 g, 11.3
Preparation of (()-3-Diphenylphosphino-2-(indolin-1-yl)ben-
zyl Acetate ((()-1d). A mixture of 9 (0.45 g, 1.10 mmol) and acetic
anhydride (0.24 mL, 2.20 mmol) in triethylamine (22 mL) was
stirred at room temperature for 2 h in the presence of a catalytic
amount of DMAP (0.01 g, 0.11 mmol). After the mixture was
diluted with 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 column chromatography
(elution with n-hexane:EtOAc ) 8:1): 0.48 g, 1.07 mmol, 97%;
mp 106-107 °C; 1H NMR (CDCl3) δ 1.97 (s, 3H), 3.04-3.10 (m,
2H), 3.63-3.80 (m, 2H), 4.91 (t, J ) 13.2 Hz, 2H), 5.67 (d, J )
7.7 Hz, 1H), 6.52 (t, J ) 7.3 Hz, 1H), 6.71 (t, J ) 7.6 Hz, 1H),
7.00-7.35 (m, 10H), 7.45 (dd, J ) 0.8 and 7.5 Hz, 1H); 13C NMR
(CDCl3) δ 21.3, 29.3, 54.2 (d, JCP ) 5.9 Hz), 63.0 (d, JCP ) 2.2
Hz), 106.8, 117.6, 124.7, 127.4, 128.2, 128.6-129.0 (m), 131.3,
134.1-135.0 (m), 137.1-137.2 (m), 137.9 (d, JCP ) 12.7 Hz), 142.5
(d, JCP ) 11.4 Hz), 145.5 (d, JCP ) 22.9 Hz), 124.1, 151.0, 171.0;
31P NMR (CDCl3) δ -15.2; EI-MS m/z (relative intensity) 451 (M+,
100); HRMS (FAB-MS) m/z calcd for C28H25O2NP 451.1701, found
451.1679; HPLC Daicel CHIRALCEL OD + OD-H (0.46 φ × 25
cm × 2, UV 254 nm, hexane:ethanol ) 99:1, 0.50 mL/min), tR )
23.2 (CD, λext (∆ꢀ) 254 (+)) and 24.5 min (CD, λext (∆ꢀ) 254 (-));
X-ray diffraction analysis data of (()-1d (Figure S4). Colorless
needle crystals from n-hexane, C28H25O2NP, orthorhombic space
group Pbca, a ) 18.401(6) Å, b ) 35.757(11) Å, c ) 7.264(3) Å,
V ) 4779.(3) Å3, Z ) 8, F ) 1.255 g/cm3, µ (Cu KR) ) 12.2
cm-1. The structure was solved by the direct method of full-matrix
least-squares, where the final R and Rw were 0.047 and 0.099 for
1620 reflections, respectively.
Typical Procedure for Preparation and Separation of Dia-
stereomeric Complex Mixtures (aS,S)-11 and (aR,S)-12. A
mixture of (()-1 (0.50 mmol) and (S)-(+)-di-µ-chlorobis[2-
[(dimethylamino)ethyl]phenyl-C2,N]dipalladium(II) ((S)-(+)-10)
(0.15 g, 0.25 mmol) in toluene (1.0 mL) was stirred at room
temperature for 1 h. The mixture was concentrated under reduced
pressure, and the residue was purified by silica gel column
chromatography (elution with n-hexane:Et2O ) 2:1) to separate
the diastereomeric mixture of (aS,S)-11 and (aR,S)-12.
(aS,S)-(+)-[Dimethyl(1-(1-phenyl)ethyl)aminato-C2,N]-[1-(in-
dolin-1-yl)(2-naphthyl)diphenylphosphine]palladium(II) chlo-
ride ((aS,S)-(+)-11a): 46%; Rf ) 0.68 (Et2O) (less polar agent on
silica gel column chromatography); [R]25D +92.8° (c 1.01, CHCl3);
1H NMR (CDCl3) δ 1.44 (d, J ) 6.5 Hz, 3H), 2.50 (d, J ) 2.4 Hz,
3H), 2.71 (d, J ) 2.1 Hz, 3H), 2.99-3.29 (m, 2H), 3.70-3.93 (m,
2H), 4.36 (s, 1H), 5.47 (d, J ) 6.8 Hz, 2H), 6.36-6.55 (m, 4H),
6.80-6.88 (m, 2H), 7.00-7.10 (m, 3H), 7.19-7.25 (m, 2H), 7.37-
7.48 (m, 6H), 7.60-7.69 (m, 2H), 7.78 (d, J ) 8.6 Hz, 1H), 7.87-
7.99 (m, 3H); 13C NMR (CDCl3) δ 16.7, 29.4, 44.2, 49.1, 55.5,
74.2, 109.9, 117.7, 122.5, 123.7 (d, JCP ) 8.0 Hz), 124.7-124.9
(m), 125.7, 126.6, (d, JCP ) 5.4 Hz), 127.2-130.1 (m), 130.5 (d,
JCP ) 7.1 Hz), 131.1 (d, JCP ) 46.7 Hz), 135.8-137.5 (m), 143.5
(d, JCP ) 8.3 Hz), 149.7, 151.8, 153.6; 31P NMR (CDCl3) δ 33.3;
FAB-MS m/z (relative intensity) 718 (M+, 7), 683 ([M - Cl]+,
65); HRMS (FAB-MS) m/z calcd for C40H38ClN2PPd + H
719.1586, found 719.1638.
1
mmol, 97%; mp 133-134 °C; H NMR (CDCl3) δ 2.69 (s, 6H),
2.98-3.03 (m, 2H), 3.54-3.63 (m, 2H), 5.83 (d, J ) 7.8 Hz, 1H),
6.52 (dt, J ) 0.7 and 6.9 Hz, 1H), 6.75 (t, J ) 7.4 Hz, 1H), 6.85
(ddd, J ) 1.5, 3.1, and 7.5 Hz, 1H), 6.92 (s, 1H), 7.01 (d, J ) 7.1
Hz, 1H), 7.18-7.24 (m, 5H), 7.32-7.35 (m, 5H), 6.52 (dd, J )
1.3 and 7.8 Hz, 1H); 13C NMR (CDCl3) δ 29.2, 42.9, 54.6 (d, JCP
) 4.4 Hz), 107.9, 117.6, 124.5, 127.4-129.8 (m), 133.2, 134.5 (d,
JCP ) 20.5 Hz), 136.1 (d, JCP ) 3.0 Hz), 137.6 (d, JCP ) 11.7 Hz),
138.3 (d, JCP ) 12.7 Hz), 141.8 (d, JCP ) 8.7 Hz), 144.5 (d, JCP
)
22.5 Hz), 151.9; 31P NMR (CDCl3) δ -14.8; EI-MS m/z (relative
intensity) 449 (M+, 20); HRMS (FAB-MS) m/z calcd for C29H28N3P
+ H 450.2099, found 450.2074.
Preparation of 3-Diphenylphosphino-2-(indolin-1-yl)benzal-
dehyde (8). A mixture of 7 (0.45 g, 1.00 mmol) and aqueous HCl
(10.0 mL, 6 M) in THF (10 mL) was stirred at 0 °C for 5 h. The
mixture was diluted with ether, then the organic layer was washed
with 6 M aqueous HCl and brine, dried over MgSO4, and
concentrated under reduced pressure. The residue was purified by
silica gel column chromatography (elution with n-hexane:EtOAc
) 8:1): 0.25 g, 0.62 mmol, 62%; mp 134-136 °C; 1H NMR
(CDCl3) δ 3.10 (dd, J ) 7.7 and 9.5 Hz, 2H), 3.66 (q, J ) 9.6 Hz,
1H), 3.86-3.94 (m, 1H), 5.80 (d, J ) 7.8 Hz, 1H), 6.58 (t, J ) 7.2
Hz, 1H), 6.74 (t, J ) 7.4 Hz, 1H), 7.05 (d, J ) 7.2 Hz, 1H), 7.20-
7.40 (m, 12H), 7.97 (dd, J ) 1.7 and 7.5 Hz, 1H), 10.0 (s, 1H);
13C NMR (CDCl3) δ 28.9, 56.3 (d, JCP ) 5.9 Hz), 106.6, 118.0,
124.5, 127.3, 127.9-128.9 (m), 130.3, (d, JCP ) 5.2 Hz), 135.4
(d, JCP ) 3.4 Hz), 136.0 (d, JCP ) 11.5 Hz), 136.7 (d, JCP ) 12.3
Hz), 140.2, 142.9 (d, JCP ) 13.8 Hz), 150.5 (d, JCP ) 22.7 Hz),
152.1, 190.4; 31P NMR (CDCl3) δ -16.2; EI-MS m/z (relative
intensity) 407 (M+, 100); HRMS (FAB-MS) m/z calcd for C27H22-
NOP 407.1439, found 407.1429.
Preparation of 3-Diphenylphosphino-2-(indolin-1-yl)benzyl
Alcohol (9). A mixture of 8 (1.02 g, 2.50 mmol) and sodium
borohydride (0.47 g, 12.5 mmol) in MeOH (25 mL) was stirred at
0 °C for 1 h. After the mixture was diluted with 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 column chromatography (elution with n-hexane:EtOAc
) 6:1): 0.94 g, 2.30 mmol, 92%; mp 134-135 °C; 1H NMR
(CDCl3) δ 1.93 (t, J ) 5.2 Hz, 2H), 3.01-3.07 (m, 2H), 3.51-
3.74 (m, 2H), 4.35-4.47 (m, 2H), 5.67 (d, J ) 7.7 Hz, 1H), 6.52
(dt, J ) 0.8 and 7.3 Hz, 1H), 6.70 (t, J ) 7.3 Hz, 1H), 6.95-7.02
(m, 2H), 7.16-7.34 (m, 11H), 7.54 (dd, J ) 0.9 and 7.6 Hz, 1H);
J. Org. Chem, Vol. 71, No. 19, 2006 7351

Mino et al.
(aR,S)-(-)-[Dimethyl(1-(1-phenyl)ethyl)aminato-C2,N]-[1-(in-
dolin-1-yl)(2-naphthyl)diphenylphosphine]palladium(II) chlo-
ride ((aR,S)-(-)-12a): 46%; Rf ) 0.61 (Et2O) (more polar agent
(aS,S)-(+)-[Dimethyl(1-(1-phenyl)ethyl)aminato-C2,N]-[1-(in-
dolin-1-yl)-6-trifluoromethyl(2-phenyl)diphenylphosphine]pal-
ladium(II) chloride ((aS,S)-(+)-11c): 45%; Rf ) 0.50 (Et2O) (less
polar agent on silica gel column chromatography); [R]25D +109.9°
on silica gel column chromatography); [R]25 -192.5° (c 1.00,
D
1
1
CHCl3); H NMR (CDCl3) δ 1.86 (d, J ) 6.4 Hz, 3H), 2.69 (d, J
(c 1.01, CHCl3); H NMR (CDCl3) δ 1.41 (d, J ) 6.6 Hz, 3H),
) 1.3 Hz, 3H), 2.76 (d, J ) 3.3 Hz, 3H), 3.12-3.34 (m, 2H), 3.62
(quint, J ) 6.0 Hz, 1H), 3.86-3.96 (m), 4.99 (d, J ) 7.7 Hz, 1H),
5.45 (t, J ) 9.1 Hz, 1H), 6.29-6.48 (m, 4H), 6.79-7.06 (m, 6H),
7.15-7.20 (m, 1H), 7.33-7.41 (m, 5H), 7.47-7.56 (m), 7.74 (d,
J ) 8.6 Hz, 1H), 7.86 (d, J ) 8.0 Hz, 1H), 8.26-8.30 (m); 13C
NMR (CDCl3) δ 23.1, 29.2, 47.0, 50.5, 55.0, 75.6 (d, JCP ) 3.2
Hz), 109.0, 117.6, 122.1, 123.5, 123.9, 124.6-125.7 (m), 126.5
(d, JCP ) 16.8 Hz), 127.0 (d, JCP ) 9.2 Hz), 127.4 (d, JCP ) 10.8
Hz), 128.0-128.7 (m), 129.2, 129.5-130.8 (m), 131.3, 135.5,
135.6, 136.4-136.9 (m), 137.1 (d, JCP ) 11.2 Hz), 143.0 (d, JCP
) 7.3 Hz), 148.3, 151.5, 155.1; 31P NMR (CDCl3) δ 34.4; FAB-
MS m/z (relative intensity) 718 (M+, 10), 683 ([M - Cl]+, 75);
HRMS (FAB-MS) m/z calcd for C40H38ClN2PPd + H 719.1586,
found 719.1631; X-ray diffraction analysis data of (aR,S)-(-)-12a
(Figure S6). Yellow prismatic crystals from ethanol:n-hexane,
C40H38ClN2PPd, orthorhombic space group P212121, a ) 10.4700-
(13) Å, b ) 15.561(2) Å, c ) 22.835(3) Å, V ) 3720.3(9) Å3, Z
) 4, F ) 1.285 g/cm3, µ (Mo KR) ) 6.42 cm-1. The structure was
solved by the direct method of full-matrix least-squares, where the
final R and Rw were 0.056 and 0.074 for 4346 reflections,
respectively.
2.45 (d, J ) 2.4 Hz, 3H), 2.94 (d, J ) 2.9 Hz, 3H), 2.97-3.24 (m,
2H), 3.61-3.71 (m, 1H), 5.04 (s, 1H), 5.24 (s, 1H), 6.34-6.47
(m, 4H), 6.82-6.96 (m, 5H), 7.13 (t, J ) 7.0 Hz, 1H), 7.37-7.55
(m, 7H), 7.77 (d, J ) 7.7 Hz, 1H), 8.09-8.15 (m, 2H); 13C NMR
(CDCl3) δ 13.8, 29.6 (d, JCP ) 18.0 Hz), 42.9, 49.2 (d, JCP ) 2.7
Hz), 55.6 (d, JCP ) 2.0 Hz), 73.7 (d, JCP ) 2.6 Hz), 108.3, 117.6,
123.1 (d, JCP ) 10.1 Hz), 124.0-132.0 (m), 135.6 (d, JCP ) 11.4
Hz), 136.7-137.3 (m), 142.8 (d, JCP ) 7.0 Hz), 143.6 (d, JCP
)
9.2 Hz), 150.2, 150.9, 152.9; 31P NMR (CDCl3) δ 33.9; FAB-MS
m/z (relative intensity) 736 (M+, 10), 701 ([M - Cl]+, 35); HRMS
(FAB-MS) m/z calcd for C37H35ClF3N2PPd 736.1213, found
736.1158.
(aR,S)-(-)-[Dimethyl(1-(1-phenyl)ethyl)aminato-C2,N]-[1-(in-
dolin-1-yl)-6-trifluoromethyl(2-phenyl)diphenylphosphine]pal-
ladium(II) chloride ((aR,S)-(-)-12c): 45%; Rf ) 0.39 (Et2O) (more
polar agent on silica gel column chromatography); [R]25D -147.6°
1
(c 1.00, CHCl3); H NMR (CDCl3) δ 1.89 (d, J ) 6.4 Hz, 3H),
2.68 (d, J ) 1.5 Hz, 3H), 2.84 (d, J ) 3.5 Hz, 3H), 3.06-3.24 (m,
2H), 3.55 (quint, J ) 6.2 Hz, 1H), 3.81 (q, J ) 10.1 Hz, 1H), 4.95
(d, J ) 7.6 Hz, 1H), 5.86 (s, 1H), 6.29-6.42 (m, 4H), 6.77-6.89
(m, 5H), 6.96-7.05 (m, 2H), 7.33-7.54 (m, 7H), 7.75 (d, J ) 7.7
Hz, 1H), 8.28-8.33 (m, 2H); 13C NMR (CDCl3) δ 13.8, 24.6, 29.5,
48.3, 51.3 (d, JCP ) 3.0 Hz), 55.6, 76.5 (d, JCP ) 3.2 Hz), 108.3,
118.0, 122.2-124.6 (m), 125.1 (d, JCP ) 6.2 Hz), 125.5-126.4
(aS,S)-(+)-[Dimethyl(1-(1-phenyl)ethyl)aminato-C2,N]-[1-(in-
dolin-1-yl)-6-methyl(2-phenyl)diphenylphosphine]palladium-
(II) chloride ((aS,S)-(+)-11b): 45%; Rf ) 0.53 (Et2O) (less polar
agent on silica gel column chromatography); [R]25D +94.8° (c 0.51,
(m), 127.2 (d, JCP ) 9.3 Hz), 128.1-128.4 (m), 129.1 (d, JCP
)
1
CHCl3); H NMR (CDCl3) δ 1.42 (d, J ) 6.5 Hz, 3H), 1.90 (s,
10.0 Hz), 130.3-131.9 (m), 135.8 (d, JCP ) 11.7 Hz), 137.0 (d,
JCP ) 12.2 Hz), 137.3 (d, JCP ) 5.2 Hz), 138.2 (d, JCP ) 11.2 Hz),
3H), 2.49 (d, J ) 2.3 Hz, 3H), 2.74 (d, J ) 1.8 Hz, 3H), 2.86-
3.48 (m, 3H), 3.96 (d, J ) 2.4 Hz, 1H), 4.39 (s, 1H), 5.51 (s, 1H),
6.36-6.51 (m, 4H), 6.80-7.43 (m, 7H), 7.57 (t, J ) 8.9 Hz, 2H),
7.95 (t, J ) 8.8 Hz, 2H); 13C NMR (CDCl3) δ 16.4, 19.2, 29.4,
44.1, 49.3, 54.3, 74.2, 109.0, 117.6, 122.7, 123.8 (d, JCP ) 11.2
142.7-143.4 (m), 144.1 (d, JCP ) 8.0 Hz), 147.9, 150.2 (d, JCP
)
1.4 Hz), 155.8 (d, JCP ) 2.0 Hz); 31P NMR (CDCl3) δ 34.9; FAB-
MS m/z (relative intensity) 736 (M+, 10), 701 ([M - Cl]+, 50);
HRMS (FAB-MS) m/z calcd C37H35ClF3N2PPd 736.1213, found
736.1221. X-ray diffraction analysis data of (aR,S)-(-)-12c (Figure
S8). Yellow prismatic crystals from ethanol:n-hexane, C37H35-
ClF3N2PPd, orthorhombic space group P212121, a ) 9.2400(10)
Å, b ) 14.715(2) Å, c ) 27.222(4) Å, V ) 3701.4(8) Å3, Z ) 8,
F ) 1.223 g/cm3, µ (Mo KR) ) 6.58 cm-1. The structure was solved
by the direct method of full-matrix least-squares, where the final
R and Rw were 0.065 and 0.086 for 4483 reflections, respectively.
Hz), 125.0 (d, JCP ) 6.2 Hz), 126.7-126.8 (m), 127.6 (d, JCP
10.6 Hz), 128.0 (d, JCP ) 10.2 Hz), 128.6-131.8 (m), 134.9,
135.8-137.7 (m), 138.4, 139.0 (d, JCP ) 6.0 Hz), 144.0 (d, JCP
)
)
8.8 Hz), 149.9, 150.7, 153.6; 31P NMR (CDCl3) δ 33.1; FAB-MS
m/z (relative intensity) 682 (M+, 5) 647 ([M - Cl]+, 25); HRMS
(FAB-MS) m/z calcd for C37H38ClN2PPd 682.1496, found 682.1492;
X-ray diffraction analysis data of (aS,S)-(+)-11b (Figure S7).
Yellow prismatic crystals from ethanol:n-hexane, C37H38ClN2PPd,
monoclinic space group C2, a ) 38.3957(12) Å, b ) 9.6498(3) Å,
c ) 9.6342(3) Å, V ) 3499.74(19) Å3, Z ) 4, F ) 1.297 g/cm3, µ
(Mo KR) ) 6.78 cm-1. The structure was solved by the direct
method of full-matrix least-squares, where the final R and Rw were
0.0600 and 0.1932 for 6992 reflections, respectively.
(aS,S)-(+)-[Dimethyl-(1-phenylethyl)aminato-C2,N]-[3-diphe-
nylphosphino-2-(indolin-1-yl)benzyl acetate]palladium(II) chlo-
ride ((aS,S)-(+)-11d): 47%; Rf ) 0.42 (Et2O) (less polar agent on
silica gel column chromatography); [R]25D +70.5° (c 0.5, CHCl3);
1H NMR (CDCl3) δ 1.40 (d, J ) 6.5 Hz, 3H), 1.98 (s, 3H), 2.48
(d, J ) 2.5 Hz, 3H), 2.73 (s, 3H), 2.88-3.38 (m, 2H), 3.39-3.49
(m, 1H), 3.92 (s, 1H), 4.27 (s, 1H), 4.71 (dd, J ) 13.3 and 20.1
Hz, 2H), 5.60 (s, 1H), 6.39-6.44 (m, 4H), 6.81-6.94 (m, 3H),
7.05-7.10 (m, 2H), 7.19-7.72 (m, 9H), 7.91-7.97 (m, 2H); 13C
NMR (CDCl3) δ 16.5, 21.0, 29.4, 44.2, 49.4 (d, JCP ) 2.6 Hz),
55.8, 62.0 (d, JCP ) 1.9 Hz), 74.3 (d, JCP ) 2.7 Hz), 109.0, 118.2,
122.7, 123.9, 125.0 (d, JCP ) 6.2 Hz), 126.7, 127.7 (d, JCP ) 9.1
Hz), 127.7 (d, JCP ) 10.5 Hz), 128.1 (d, JCP ) 10.1 Hz), 128.2,
128.6, 128.9, 130.2 (dd, JCP ) 2.2 and 21.7 Hz), 130.6, 131.2, 132.8
(d, JCP ) 11.8 Hz), 133.2, (d, JCP ) 4.3 Hz), 136.0 (d, JCP ) 11.3
Hz), 136.8 (d, JCP ) 12.2 Hz), 137.2-137.4 (m), 138.4, 139.1,
144.3 (d, JCP ) 9.2 Hz), 149.7, 150.8, 153.7, 170.5; 31P NMR
(CDCl3) δ 33.1; FAB-MS m/z (relative intensity) 740 (M+, 5);
HRMS (FAB-MS) m/z calcd for C39H40ClN2O2PPd 740.1562, found
740.1513; X-ray diffraction analysis data of (aS,S)-(+)-11d (Figure
S8). Yellow prismatic crystals from acetone:n-hexane mixed
solvent, C39H40ClN2O2PPd, monoclinic space group C2, a )
39.149(8) Å, b ) 9.736(2) Å, c ) 9.566(2) Å, â ) 96.414(5)°, V
) 3623.3(13) Å3, Z ) 4, F ) 1.359 g/cm3, µ (Mo KR) ) 6.65
cm-1. The structure was solved by the direct method of full-matrix
(aR,S)-(-)-[Dimethyl(1-(1-phenyl)ethyl)aminato-C2,N]-[1-(in-
dolin-1-yl)-6-methyl(2-phenyl)diphenylphosphine]palladium-
(II) chloride ((aR,S)-(-)-12b): 42%; Rf ) 0.36 (Et2O) (more polar
agent on silica gel column chromatography); [R]25D -139.4° (c 0.52,
CHCl3); 1H NMR (CDCl3) δ 1.84 (s, 3H), 1.86 (s, 3H), 2.68 (d, J
) 1.6 Hz, 3H), 2.79 (d, J ) 3.3 Hz, 3H), 2.98-3.19 (m, 2H), 3.54-
3.69 (m, 2H), 5.04 (d, J ) 6.9 Hz, 1H), 5.46 (s, 1H), 6.35-6.44
(m, 4H), 6.78-7.08 (m, 7H), 7.14 (dt, J ) 2.0 and 7.6 Hz, 1H),
7.23-7.25 (m, 2H), 7.42-7.49 (m, 5H), 8.24 (s, 1H); 13C NMR
(CDCl3) δ 19.7 (d, JCP ) 1.4 Hz), 23.8, 29.5, 30.1, 47.6, 51.0 (d,
JCP ) 2.9 Hz), 108.4, 117.8, 122.4, 123.8, 124.3, 125.1 (d, JCP
)
6.1 Hz), 126.7-128.8 (m), 129.9 (d, JCP ) 2.3 Hz), 130.6 (d, JCP
) 2.2 Hz), 131.2-131.3 (m), 131.9, 135.1 (d, JCP ) 2.1 Hz), 135.7
(d, JCP ) 11.5 Hz), 137.2 (d, JCP ) 12.2 Hz), 138.2 (d, JCP ) 11.1
Hz), 139.1 (d, JCP ) 6.4 Hz), 139.1 (d, JCP ) 57.6 Hz), 144.0 (d,
JCP ) 8.1 Hz), 148.5, 150.6, 155.5 (d, JCP ) 2.0 Hz); 31P NMR
(CDCl3) δ 34.1; FAB-MS m/z (relative intensity) 682 (M+, 5), 647
([M - Cl]+, 15); HRMS (FAB-MS) m/z calcd for C37H38ClN2PPd
682.1496, found 682.1558.
7352 J. Org. Chem., Vol. 71, No. 19, 2006

Aminophosphines with Chiral C(aryl)-N(amine) Bonds
least-squares, where the final R and Rw were 0.050 and 0.055 for
36582 reflections, respectively.
(c 0.83, CHCl3); HPLC (Daicel CHIRALCEL OD, 0.46 φ × 25
cm, UV 254 nm), tR ) 15.3 min (hexane:ethanol ) 99:1, 0.40 mL/
min) (CD, λext (∆ꢀ) 254 (-)).
(aR,S)-(-)-[Dimethyl-(1-phenylethyl)aminato-C2,N]-[3-diphe-
nylphosphino-2-(indolin-1-yl)benzyl acetate]palladium(II) chlo-
ride ((aR,S)-(-)-12d): 45%; Rf ) 0.32 (Et2O) (more polar agent
(aR)-(+)-3-Diphenylphosphino-2-(indolin-1-yl)benzyl acetate
((aR)-(+)-1d): 98% yield from (aR,S)-12d; 99.2% ee; [R]25
D
on silica gel column chromatography); [R]25 -100.6° (c 0.5,
+35.1° (c 0.96, CHCl3); HPLC (Daicel CHIRALCEL OD + OD-
H, 0.46 φ × 25 cm × 2, UV 254 nm), tR ) 45.5 min (hexane:
ethanol ) 99:1, flow ) 0.25 mL/min) (CD, λext (∆ꢀ) 254 (+)).
Elucidation of the Thermal Racemization of Optically Active
1. A small amount of optically active (aS)-1 or (aR)-1 was dissolved
in toluene at room temperature. The solution was kept at a constant
temperature in the thermostat oil bath; small portion was taken out
every passage of times, and the transitions of enantiomeric excess
were measured by chiral HPLC analysis.
D
1
CHCl3); H NMR (CDCl3) δ 1.85 (d, J ) 6.4 Hz, 3H), 1.95 (s,
3H), 2.67 (s, 3H), 2.79 (d, J ) 3.2 Hz, 3H), 3.01-3.23 (m, 2H),
3.57-3.67 (m, 2H), 4.68 (dd, J ) 13.4 and 15.4 Hz, 2H), 5.07 (d,
J ) 7.1 Hz, 1H), 5.49 (s, 1H), 6.35-6.45 (m, 4H), 6.78-6.96 (m,
6H), 7.19-7.30 (m, 2H), 7.30-7.51 (m, 6H), 8.24 (s, 2H); 13C
NMR (CDCl3) δ 21.3, 23.8, 29.5, 47.7, 51.0 (d, JCP ) 2.9 Hz),
55.8, 62.9 (d, JCP ) 1.8 Hz), 76.1 (d, JCP ) 3.1 Hz), 108.4, 118.5,
122.5, 124.2 (d, JCP ) 23.6 Hz), 125.1 (d, JCP ) 6.1 Hz), 126.8,
127.2 (d, JCP ) 9.3 Hz), 127.9 (d, JCP ) 10.9 Hz), 128.5, 128.8 (d,
JCP ) 10.0 Hz), 130.1 (d, JCP ) 2.3 Hz), 130.8 (d, JCP ) 2.1 Hz),
130.9, 131.5, 133.1 (d, JCP ) 1.8 Hz), 133.6 (d, JCP ) 4.8 Hz),
135.8 (d, JCP ) 11.5 Hz), 137.1-137.4 (m), 138.1 (d, JCP ) 11.2
Hz), 139.4, 140.1, 144.4 (d, JCP ) 8.5 Hz), 148.5, 150.8, 155.5 (d,
JCP ) 2.0 Hz), 170.9; 31P NMR (CDCl3) δ 34.2; FAB-MS m/z
(relative intensity) 740 (M+, 3); HRMS (FAB-MS) m/z calcd for
C39H40ClN2O2PPd 740.1562, found 740.1584.
Preparation of Palladium Complex (()-13. To a solution of
PdCl2(MeCN)2 (0.026 g, 0.10 mmol) in a CHCl3 (1.0 mL) was
added (()-1b (0.039 g, 0.10 mmol) at room temperature and stirred
for 30 min. The reaction mixture was filtered and evaporated under
reduced pressure: 82%; mp 145-147 °C (dec); 1H NMR (CDCl3)
δ 1.78 (s, 3H), 3.36 (ddd, J ) 3.7, 10.3, and 15.7 Hz, 1H), 3.96-
4.33 (m, 1H), 5.47 (dt, J ) 3.7 and 11.3 Hz, 1H), 6.64-6.69 (m,
1H), 7.12-7.19 (m, 2H), 7.28-7.37 (m, 4H) 7.47-7.54 (m, 4H),
7.57-7.63 (m, 2H), 7.74-7.94 (m, 4H); 31P NMR (CDCl3) δ 41.9;
FAB-MS m/z (relative intensity) 534 ([M - Cl]+, 10); HRMS
(FAB-MS) m/z calcd for C27H24Cl2NPPdCl 534.0370, found
534.0331. Anal. Calcd for C29H26Cl8NPPd: C, 43.03; H, 3.24; N,
1.73. Found: C, 43.20; H, 3.22; N, 1.68. X-ray diffraction analysis
data of 13 (Figure 2) (containing two CHCl3 molecules): yellow
plate crystals from hexane:CHCl3, C29H26Cl8NPPd, triclinic space
group P1h, a ) 8.652(3) Å, b ) 10.517(3) Å, c ) 18.683(6) Å, R
) 92.460(4)°, â ) 97.8730(4)°, γ ) 106.201(4)°, V ) 1611.3(8)
Å3, Z ) 2, F ) 1.668 g/cm3, µ (Mo KR) ) 13.11 cm-1. The
structure was solved by the direct method of full-matrix least-
squares, where the final R and Rw were 0.095 and 0.084 for 9766
reflections, respectively.
Typical Procedure for the Preparation of Optically Active
Atropisomers 1. To an individual diastereomer (aS,S)-11 or (aR,S)-
12 (0.02 mmol) was added 0.1 M solution of ethylenediamine in
chloroform (0.4 mL, 0.04 mmol) at room temperature, and stirred
for 10 min. The mixture was concentrated under reduced pressure,
and the residue was purified by silica gel column chromatography
(elution with n-hexane/EtOAc ) 8/1) to afford the optically active
(aS)-1 or (aR)-1.
(aS)-(+)-1-[2′-(Diphenylphosphino)-1′-naphthalenyl]-2,3-di-
hydro-1H-indole ((aS)-(+)-1a): 98% from (aS,S)-11a; >99% ee;
[R]25 +18.2° (c 0.11, CHCl3); HPLC (Daicel CHIRALCEL OJ,
D
0.46 φ × 25 cm, UV 254 nm), tR ) 12.9 min (hexane:ethanol )
90:10, 0.50 mL/min) (CD, λext (∆ꢀ) 254 (-)).
(aR)-(-)-1-[2′-(Diphenylphosphino)-1′-naphthalenyl]-2,3-di-
hydro-1H-indole ((aR)-(-)-1a): 93% from (aR,S)-12a; 99.1% ee;
General Procedure for the Palladium-Catalyzed Allylic Alky-
lation. To a mixture of [Pd(η3-C3H5)Cl]2 (0.01 mmol, 3.9 mg),
chiral aminophosphine ligand 1 (0.02 mmol), and LiOAc (0.01
mmol, 1 mg) in a solvent (0.4 mL) were added BSA (0.6 mmol,
0.15 mL) and racemic allylic ester 14 (0.2 mmol, 50.7 mg) at room
temperature under an Ar atmosphere. After 30 min, dimethyl
malonate (0.6 mmol, 0.07 mL) was added at the desired temper-
ature. After 24 h, the reaction mixture was diluted with 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. (R)-Methyl-
2-carbomethoxy-3,5-diphenylpent-4-enonate ((R)-16):15b (Table
[R]25 -18.1° (c 0.11, CHCl3); HPLC (Daicel CHIRALCEL OJ,
D
0.46 φ × 25 cm, UV 254 nm), tR ) 34.0 min (hexane:ethanol )
90:10, 0.50 mL/min) (CD, λext (∆ꢀ) 254 (+)).
(aS)-(+)-1-[2′-(Diphenylphospino)-6′-methylphenyl]-2,3-dihy-
dro-1H-indole ((aS)-(+)-1b): 91% from (aS,S)-11b; >99% ee;
[R]25D +19.1° (c 0.26, CHCl3); HPLC (Daicel CHIRALPAK AD-H
× 2, 0.46 φ × 25 cm × 2, UV 254 nm), tR )36.0 min (hexane:
ethanol ) 99.7:0.3, 0.30 mL/min) (CD, λext (∆ꢀ) 254 (-)).
(aR)-(-)-1-[2′-(Diphenylphospino)-6′-methylphenyl]-2,3-dihy-
dro-1H-indole ((aR)-(-)-1b): 89% from (aR,S)-12b; >99% ee;
[R]25D -19.2° (c 0.27, CHCl3); HPLC (Daicel CHIRALPAK AD-H
× 2, 0.46 φ × 25 cm × 2, UV 254 nm), tR )61.0 min (hexane:
ethanol ) 99.7:0.3, 0.15 mL/min) (CD, λext (∆ꢀ) 254 (+)).
(aS)-(-)-1-[2′-(Diphenylphosphino)-6′-trifluoromethylphenyl]-
1
1, entry 4) 91%; 95% ee; H NMR (CDCl3) δ 3.52 (s, 3H), 3.71
(s, 3H), 3.95 (d, J ) 11.0 Hz, 1H), 4.28 (dd, J ) 8.6 and 11.0 Hz,
1H), 6.33 (dd, J ) 8.6 and 15.9 Hz, 1H), 6.49 (d, J ) 15.9 Hz,
1H), 7.22-7.34 (m, 10H).
indoline ((aS)-(-)-1c): 91% from (aS,S)-11c; >99% ee; [R]25
D
-32.4° (c 0.86, CHCl3); HPLC (Daicel CHIRALPAK AD-H × 2,
0.46 φ × 25 cm × 2, UV 254 nm), tR ) 32.1 min (hexane:ethanol
) 99.7:0.3, 0.25 mL/min) (CD, λext (∆ꢀ) 254 (-)).
(aR)-(+)-1-[2′-(Diphenylphosphino)-6′-trifluoromethylphenyl]-
indoline ((aR)-(+)-1c): 95% yield from (aR,S)-12c; >99% ee;
[R]25D +32.4° (c 0.81, CHCl3); HPLC (Daicel CHIRALPAK AD-H
× 2, 0.46 φ × 25 cm × 2, UV 254 nm), tR ) 57.8 min (hexane:
ethanol ) 99.7:0.3, 0.15 mL/min) (CD, λext (∆ꢀ) 254 (+)).
(aS)-(-)-3-Diphenylphosphino-2-(indolin-1-yl)benzyl acetate
((aS)-(-)-1d): 98% yield from (aS,S)-11d; >99% ee; [R]25D -35.2°
Supporting Information Available: ORTEP drawing of (()-
1a-d, 9, 12a, 11b, 12c, and 11d (Figures S1-S9); data of thermal
racemization (Figures S10-S13) of (()-1a-d; NMR spectra of
all compounds; copy of HPLC charts of (aS)- and (aR)-1a-d, 9,
and (R)-16; and X-ray crystallographic file (CIF) for (()-1a-d, 9,
11b, 11d, 12a, 12c, and 13. This material is available free of charge
via the Internet at http://pubs.acs.org.
JO061261F
J. Org. Chem, Vol. 71, No. 19, 2006 7353