Synthesis of a new type of chiral amino phosphine ligands for asymmetric catalysis

Article abstract of DOI:10.1016/S0957-4166(02)00324-5

This article describes the synthesis of a new type of chiral amino phosphine ligands from an amino naphthol starting material derived by asymmetric 1-aminoalkylation of 2-naphthol with (R)-1-phenylethylamine and benzaldehyde. The asymmetric induction properties of the ligands in the Pd(0)-catalyzed allylic substitution of 1,3-diphenylprop-2-en-1-yl acetate with dimethyl malonate has also been investigated, with near-quantitative yields and ee of up to 72.2% of the product being obtained under the optimized reaction conditions.

Full text of DOI:10.1016/S0957-4166(02)00324-5

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 1291–1297
Synthesis of a new type of chiral amino phosphine ligands for
asymmetric catalysis
Yi Wang, Xin Li and Kuiling Ding*
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, the Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai 200032, China
Received 16 May 2002; accepted 14 June 2002
Abstract—This article describes the synthesis of a new type of chiral amino phosphine ligands from an amino naphthol starting
material derived by asymmetric 1-aminoalkylation of 2-naphthol with (R)-1-phenylethylamine and benzaldehyde. The asymmetric
induction properties of the ligands in the Pd(0)-catalyzed allylic substitution of 1,3-diphenylprop-2-en-1-yl acetate with dimethyl
malonate has also been investigated, with near-quantitative yields and ee of up to 72.2% of the product being obtained under the
optimized reaction conditions. © 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
Palmieri et al.3 and Wang et al.4 developed a practical
condensation reaction for the stereoselective synthesis
of optically pure amino naphthol 1 from 2-naphthol,
benzaldehyde, and commercially available (R)-1-
phenylethylamine. This ligand exhibited fairly good
enantioselectivity in the asymmetric addition of
diethylzinc to aromatic aldehydes.5 Ligand 2, an N-
methylated analogue of 1, showed even higher enan-
tioselectivity than 1 under the same reaction conditions,
with ee of up to 99.8% of secondary alcohol being
obtained.4 As part of a continuous effort to develop
N,P-ligands for enantioselective catalysis, we report in
the work presented herein the synthesis of a new type of
amino phosphine ligands 3 (based on 1), and the appli-
cation of ligands 3 in Pd-catalyzed asymmetric allylic
alkylation.
The development of novel chiral ligands remains the
most attractive area in the field of transition metal-cat-
alyzed asymmetric reactions. Chiral N,P ligands repre-
sent one important type of chirality transfer agent for
asymmetric catalysis.1 Recently, a new type of amino
phosphine ligands (MAP and H8-MAP) have been syn-
thesized and applied to Pd-catalyzed asymmetric allyla-
tion and Suzuki coupling reactions with moderate to
good asymmetric induction.2
NR2
NR2
PAr2
PAr2
2. Results and discussions
(R)-MAP
(R)-H8-MAP
2.1. Synthesis of the chiral amino phosphine ligands
Diastereomerically pure amino naphthol (R,R)-1 was
prepared according to the literature method.3 The
reductive methylation of (R,R)-1 with (CH2O)n and
NaBH4 in the presence of trifluoroacetic acid gave the
oxazine derivative (R,R)-4, rather than the expected
N-methylatedproduct(R,R)-2(Scheme1).Obviously,the
hydroxy group was very prone to reaction with the
active methylene imine intermediate. Fortunately, the
CꢀO bond of oxazine (R,R)-4 could be reduced with
LiAlH4 at 0°C to give N-methylated amino naphthol in
good yield. Treatment of (R,R)-2 with trifluoro-
NH
OH
N
N
Me
OH
R
PAr2
1
2
3
* Corresponding author. Tel.: +86-21-64163300-3424; fax: +86-21-
64166128; e-mail: kding@pub.sioc.ac.cn
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00324-5

1292
Y. Wang et al. / Tetrahedron: Asymmetry 13 (2002) 1291–1297
Ph
NH
OH
Ph
NMe
OH
Ph
N
i
ii
O
(R, R)-1
(R, R)-2
(R, R)-4
Ph
NMe
PAr2
iii
Ph
NMe
OTf
Ph
NMe
PAr2
iv
v
O
Ar = Ph, 3a
Ar = p-Tol, 3b
Ar = Ph, 6a
Ar = p-Tol, 6b
(R, R)-3
(R, R)-5
(R, R)-6
Scheme 1. Reagents and conditions: (i) 40% aq. HCHO, TFA, THF, 4 h, 90%; (ii) LiAlH4, THF, 0°C, 5 h, 81%; (iii) Tf2O, Et3N,
CH2Cl2, −78°C, 1 h, 99%; (iv) Pd(OAc)2, dppp, HP(O)Ar2, (i-Pr)2NEt, DMSO, 100°C, 12 h, 23–41%; (v) HSiCl3, Et3N, toluene,
100°C, 17 h, 30–36%.
methanesulfonic anhydride in the presence of Et3N
gave its triflate derivative (R,R)-5 in 99% yield. The
coupling reaction of (R,R)-5 with Ar2P(O)H catalyzed
the presence of NaOH to remove the acetyl group
attached to hydroxy group, affording (R,R)-8 in 80%
total yield. Treatment of (R,R)-8 with trifluoro-
methanesulfonic anhydride in the presence of Et3N
gave its triflate derivative (R,R)-9 in 93% yield. It was
found that triflate 9 underwent a coupling reaction with
Ar2P(O)H catalyzed by Pd(OAc)2/dppp to give (R,R)-
10a,b in moderate yields. Noyori et al. reported that
both an acetamide group and a phosphinyl group could
be reduced by BH3·Me2S to afford the corresponding
amino and phosphino groups, respectively.6 However,
under these reaction conditions, only the acetamide
groups of (R,R)-10a,b were reduced to give (R,R)-11a,b
by
Pd(OAc)2/dppp
(dppp=1,3-bis(diphenylphos-
phino)propane) yielded (R,R)-6a,b in 23–41% yields.
Reduction of (R,R)-6a,b with HSiCl3 in the presence of
Et3N gave the desired amino phosphine ligands (R,R)-
3a,b in 30–36% yields.
In order to develop the N-ethylated analogues of
(R,R)-3a,b, we tried an alternative approach. As shown
in Scheme 2, amino naphthol (R,R)-1 was firstly treated
with acetyl chloride in pyridine, and then hydrolyzed in
Scheme 2. Reagents and conditions: (i) AcCl, pyridine, 0°C–rt, 12 h, 85%; (ii) NaOH, CH3OH, H2O, rt, 1 h, 94%; (iii) Tf2O,
CH2Cl2, Et3N, −78°C, 4 h, 93%; (iv) Pd(OAc)2, dppp, HP(O)Ar2, (i-Pr)2NEt, DMSO, 100°C, 12–17 h, 61–64% yield; (v)
BH3·Me2S, THF, 0°C–reflux, 18 h, 70–95%; (vi) HSiCl3, Et3N, toluene, 100°C, 12 h, 51–56%.

Y. Wang et al. / Tetrahedron: Asymmetry 13 (2002) 1291–1297
1293
in 70–95% yield. Thus, the target amino phosphine
3. Conclusion
ligands (R,R)-3c,d were obtained by reduction of 11a,b
with HSiCl3/Et3N in moderate yields.
In summary, a series of novel chiral amino phosphine
ligands have been prepared from an amino phenol
which was derived through 1-aminoalkylation of 2-
naphthol with (R)-1-phenylethylamine and benzalde-
hyde. The asymmetric induction properties of these
ligands in the Pd(0)-catalyzed allylic substitution of
1,3-diphenylprop-2-en-1-yl acetate with dimethyl mal-
onate was also investigated, with near-quantitative yield
and 72.2% ee of the product being obtained under the
optimized reaction conditions.
2.2. Asymmetric induction of chiral amino phosphine
ligands 3a–d in Pd(0)-catalyzed enantioselective allylic
alkylation
Chiral N,P-ligands have been proved to be an efficient
type of ligands for asymmetric allylic alkylation reac-
tions.7,8 In order to investigate the efficiency of the
newly developed amino phosphine ligands 3a–d in
asymmetric catalysis, the Pd(0)-catalyzed allylic substi-
tution of racemic 1,3-diphenylprop-2-en-1-yl acetate 12
with dimethyl malonate was taken as a model reaction.
4. Experimental
4.1. General considerations
Table 1 shows the details of our results. The reaction
carried out in CH2Cl2 at 25°C with [Pd(C3H5)Cl]2 as
catalyst precursor, 3c as chiral ligand, and Cs2CO3 as
base yielded (S)-13 in 96% yield and 66.5% ee (entry 1).
Increasing the ratio of chiral ligand to palladium pre-
cursor led to a slight improvement in the enantioselec-
tivity of the reaction, but the yield of the product
dropped significantly (entry 2 versus 1). Examination of
solvent effects showed that the reaction proceeded in
ClCH2CH2Cl with higher enantioselectivity, but the
yield of product was only moderate (entries 3–6 versus
2). It should be noted that the absolute configuration of
the product obtained in CH3CN was switched to R
(entry 5). Therefore, the asymmetric induction proper-
ties of other N,P-ligands 3a, 3b and 3d were examined
for the same reaction in CH2Cl2, the best result of 99%
yield and 71.2% ee was obtained with the
[Pd(C3H5)Cl]2/3a catalytic complex (entries 7–9). Sub-
stitution of the reaction solvent with ClCH2CH2Cl also
gave comparable results, with 99% yield and ee of
72.2% (entry 10 versus 8).
1H NMR spectra were recorded in CDCl3 on a Bruker
AM300 spectrometers at 25°C, Chemical shifts are
reported in ppm with TMS as an internal standard
(l=0 ppm). 31P NMR spectra were recorded on a
Bruker AM300 instrument in CDCl3 with 85% H3PO4
as an external reference. Optical rotation was measured
with a PE-341 automatic polarimeter. Liquid chro-
matographic analyses were conducted on a JASCO
1580 system. IR spectra were measured on a Bio-Rad
FTS-185 spectrometer in KBr pellets. EI Mass and ESI
spectra were obtained on HP5989A and Mariner LC-
TOF spectrometers, respectively. HRMS were obtained
on a Kratos Concept 1H instrument. Elemental analy-
ses were performed using an Elemental VARIO EL
apparatus. All experiments sensitive to moisture or air
were carried out under an argon atmosphere using
standard Schlenk techniques. Commercial reagents
were used as received without further purification
unless otherwise noted. Dichloromethane, 1,2-
Table 1. Asymmetric Pd(0)-catalyzed substitution of (9)-12 with malonatea
Entry
Ligand
Solvent
Time (h)
Yieldb (%)
Eec (%)
1
2
3
4
5
6
7
8
9
3c
3cd
3c
3c
3c
3c
3d
3a
3b
3a
CH2Cl2
CH2Cl2
THF
Toluene
CH3CN
ClCH2CH2Cl
CH2Cl2
CH2Cl2
CH2Cl2
24
24
24
24
24
24
24
24
24
24
96
42
58
45
41
67
83
99
96
99
66.5
69.5
41.5
50.7
11.6e
70.2
59.7
71.2
61.5
72.2
10
ClCH2CH2Cl
a [Pd(C3H5)Cl]2:ligand:( )-12:Cs2CO3:malonate=2.5:6:100:200:200; all the reactions were carried out at 25°C.
b Isolated yield.
c Determined by HPLC on Chiralpak AD column, the absolute configuration of the product was assigned (by comparing the retention time with
the reported value as S).2k,2f
d [Pd(C3H5)Cl]2:ligand:( )-12=2.5:11:100.
e The absolute configuration of the product is R.

1294
Y. Wang et al. / Tetrahedron: Asymmetry 13 (2002) 1291–1297
dichlorethane, CH3CN were freshly distilled from cal-
cium hydride and THF, toluene from sodium ben-
zophenone ketyl. Enantiomerically pure amino
naphthol (R,R)-1 was prepared according to the
reported procedure.3
1H), 7.21–7.43 (m, 6H), 7.52–7.65 (m, 3H), 7.69–7.81
(m, 5H), 9.87 (d, J=9.2 Hz, 1H); IR (KBr pellet): w
3088 (w), 2978 (m), 1598 (m), 1510 (m), 1494 (m), 1450
(m), 1419 (s), 1249 (s), 1216 (vs), 1141 (vs), 1051 (m),
941 (s), 883 (s), 841 (s), 809 (s); EIMS (m/z): 484
([M−15]+, 56%). Anal. calcd for C27H24F3NO3S: C,
64.92; H, 4.84; N, 2.80. Found: C, 64.98; H, 5.03; N,
2.55%.
4.2. (1R)-1-Phenyl-2-((1%R)-1%-phenylethyl)-2,3-dihydro-
1H-naphtho[1,2-e][1,3]oxazine, (R,R)-43
To a solution of (R,R)-1 (2.824 g, 8 mmol) in THF (12
mL), were added 40% aqueous formaldehyde (0.6 mL)
and TFA (1 mL). The reaction mixture was stirred at
room temperature for 4 h, and then diluted and
extracted with ethyl acetate. The extracts were washed
with water, saturated aqueous NaHCO3, and brine,
respectively, dried over Na2SO4, and then concentrated
under reduced pressure. The residue was submitted to
chromatographic separation on silica gel with hexane/
EtOAc (20:1) as eluent to give a white amorphous solid
(2.641 g, 90%): [h]D20=−171.3 (c 2.785, CHCl3) (lit.:2
4.5. {(R)-[2-(Diphenylphosphinoyl)naphthalen-1-
yl]phenylmethyl}methyl((1%R)-1%-phenylethyl)amine,
(R,R)-6a
To
a mixture of (R,R)-5 (998 mg, 2 mmol),
diphenylphosphine oxide (808 mg, 4 mmol), Pd(OAc)2
(45 mg, 0.2 mmol), and dppp (124 mg, 0.3 mmol) were
added DMSO (10 mL) and diisopropylethylamine (1.8
mL, 10 mmol), and the mixture was stirred at 100°C for
12 h. After cooling to room temperature, the reaction
mixture was diluted with ethyl acetate, washed with
water twice, washed with brine, dried over Na2SO4, and
then concentrated under reduced pressure. The result-
ing residue was submitted to chromatographic separa-
tion on silica gel with hexane/EtOAc (10:1–4:1) as
eluent to give (R,R)-6a as a white solid (449 mg, 41%):
1
−132.5 (c 3.2, CHCl3)); H NMR (300 MHz, CDCl3): l
1.55 (d, J=6.2 Hz, 3H), 3.98 (q, J=6.6 Hz, 1H), 4.94
(d, J=11.0 Hz, 1H), 5.14 (dd, J=1.8, 10.6 Hz, 1H),
5.20 (s, 1H), 7.03–7.06 (m, 3H), 7.14–7.41 (m, 11H),
7.74–7.78 (m, 2H); EIMS (m/z): 367 ([M]+, 0.3%).
1
[h]2D0=+132.9 (c 0.525, CHCl3); H NMR (300 MHz,
4.3. 1-{(R)-[Methyl((1%R)-1%-phenylethyl)amino]phenyl-
methyl}naphthalen-2-ol, (R,R)-24
CDCl3): l 1.41 (d, J=6.7 Hz, 3H), 1.86 (s, 3H), 4.37 (q,
J=6.7 Hz. 1H), 6.93–6.98 (m, 3H), 7.00–7.62 (m, 16H),
7.65–7.81 (m, 7H), 9.93 (d, J=8.6 Hz, 1H); 31P NMR
(121.46 MHz, CDCl3): l 35.0; IR (KBr pellet): w 3053
(w), 2966 (w), 1598 (w), 1492 (m), 1436 (s), 1187 (s),
1115 (s), 1029 (m), 702 (vs), 694 (vs); EIMS (m/z): 446
([M−105]+, 100%). Anal. calcd for C38H34NOP: C,
82.37; H, 6.21; N, 2.54. Found: C, 82.25; H, 6.54; N,
2.47%.
To a Schlenk tube containing LiAlH4 (320 mg, 8.4
mmol) and dried THF (12 mL), was added (R,R)-3
(2.558 g, 7.0 mmol) in THF (12 mL) at 0°C. After the
mixture was stirred for 5 h, the reaction was quenched
with water. Then the reaction mixture was extracted
with ethyl acetate for three times, the combined organic
layer was washed with water, brine, dried over Na2SO4,
and concentrated under reduced pressure. The residue
was recrystallized from CH2Cl2/hexane, furnishing
white crystal (2.089 g, 81%): [h]2D0=−265.7 (c 0.49,
4.6. {(R)-[2-(Di-p-tolylphosphinoyl)naphthalen-1-
yl]phenylmethyl}methyl((1%R)-1%-phenylethyl)amine,
(R,R)-6b
1
CHCl3); H NMR (300 MHz, CDCl3): l 1.52 (m, 3H),
2.16 (m, 3H), 4.21 (brm, 1H), 5.33 (s, 1H), 7.17–7.43
(m, 11H), 7.61–7.85 (m, 5H), 14.02 (brs, 1H); IR (KBr
pellet): w 3060 (w), 3022 (w), 2995 (w), 2968 (w), 1621
(s), 1599 (s), 1452 (vs), 1267 (s), 1237 (vs), 1151 (m),
1122 (m), 1043 (m), 1027 (m), 821 (s), 751 (vs), 701 (vs);
EIMS (m/z): 367 ([M]+, 5%).
Following the same procedure for the preparation of
(R,R)-6a, reaction of (R,R)-5 with di(4-toly)phosphine
oxide afforded (R,R)-6b as an amorphous white solid
1
(yield, 23%): [h]2D0=+139.5 (c 0.555, CHCl3); H NMR
(300 MHz, CDCl3): l 1.42 (d, J=6.7 Hz, 3H), 1.78 (s,
3H), 2.39 (s, 3H), 2.44 (s, 3H), 4.37 (q, J=6.7 Hz, 1H),
6.93–7.04 (m, 3H), 7.13–7.71 (m, 21H), 9.90 (d, J=8.6
Hz, 1H); 31P NMR (121.46 MHz, CDCl3): l 35.1; IR
(KBr pellet): w 1600 (m), 1499 (m), 1455 (m), 1114 (s),
809 (s), 751 (s), 700 (s), 659 (s); EIMS (m/z): 474
([M−105]+, 53%). Anal. calcd for C40H38NOP: C, 82.87;
H, 6.61; N, 2.42. Found: C, 82.53; H, 6.80; N, 2.30%.
4.4. 1-{(R)-[Methyl((1%R)-1%-phenylethyl)amino]-
phenylmethyl}naphthalen-2-yl trifluoromethanesulfonate,
(R,R)-5
Trifluoromethanesulfonic anhydride (1 mL, 5.5 mmol)
was slowly added to a solution of (R,R)-2 (1.835 g, 5
mmol) and Et3N (3.5 mL, 25 mmol) in dried CH2Cl2
(16.3 mL) at −78°C, the reaction mixture was stirred for
1 h, then warmed to room temperature. After removal
of the solvent under reduced pressure, the resulting
residue was submitted to chromatographic separation
on silica gel with hexane/EtOAc (20:1) as eluent to give
(R,R)-5 as a light yellow solid (2.481 g, 99%): mp
4.7. {(R)-[2-(Diphenylphosphanyl)naphthalen-1-
yl]phenylmethyl}methyl((1%R)-1%-phenylethyl)amine,
(R,R)-3a
To a solution of (R,R)-6a (416 mg, 0.76 mmol) and
dried Et3N (1.5 mL, 10.6 mmol) in dried toluene (5
mL), was added HSiCl3 (1.2 mL, 10.6 mmol) at 0°C,
the reaction mixture was stirred for 0.5 h, and then
heated to 120°C under stirring for additional 17 h. The
1
71–73°C; [h]2D0=−48.1 (c 0.57, CHCl3); H NMR (300
MHz, CDCl3): l 1.45 (d, J=6.7 Hz, 3H), 2.06 (s, 3H),
4.29 (q, J=6.7 Hz, 1H), 5.86 (s, 1H), 7.13–7.16 (m,

Y. Wang et al. / Tetrahedron: Asymmetry 13 (2002) 1291–1297
1295
reaction was quenched at room temperature, with 1N
4.10. N-[(R)-(2-Hydroxynaphthalen-1-yl)phenylmethyl]-
aqueous NaOH. The mixture was filtered through
Celite, and the filtrate was extracted with ethyl acet-
ate, washed with water, brine, dried over Na2SO4,
and concentrated under reduced pressure. The residue
was submitted to chromatographic separation on sil-
ica gel with hexane/EtOAc (10:1) as eluent to give a
white amorphous solid (147 mg, 36%): [h]2D0=+135 (c
N-((1%R)-1%-phenylethyl)acetamide, (R,R)-8
To a solution of (R,R)-4 (3.019 g, 6.9 mmol) in water
(12 mL) and CH3OH (180 mL) was added NaOH
(1.2 g, 30 mmol). The mixture was stirred at room
temperature for 1 h. The solvent was removed under
reduced pressure and the resulting residue was neu-
tralized with saturated aqueous NH4Cl and extracted
three times with ethyl acetate. The combined organic
layers were washed with saturated aqueous NaHCO3,
water, brine, dried over Na2SO4, and then concen-
trated under reduced pressure. The residue was
recrystallized from a mixed solvent of THF/hexane,
affording (R,R)-8 as a white crystal (2.577 g, 94%):
mp 164°C dec.; [h]D20=−509.2 (c 0.515, CHCl3); 1H
NMR (300 MHz, CDCl3): l 2.02 (d, J=6.7 Hz, 3H),
2.36 (s, 3H), 5.25 (q, J=6.1 Hz, 1H), 6.35 (s, 1H),
6.58–6.61 (m, 3H), 6.95–7.31 (m, 11H), 7.50–7.54 (m,
2H), 9.84 (brs, 1H); IR (KBr pellet): w 1629 (m), 1596
(vs), 1576 (vs), 1516 (s), 1495 (m), 1436 (s), 1374 (s),
1273 (vs), 1160 (m), 1032 (m), 815 (s), 742 (s), 697
(vs); EIMS (m/z): 395 ([M]+, 4%). Anal. calcd for
C27H25NO2: C, 82.00; H, 6.37; N, 3.54. Found: C,
81.61; H, 6.44; N, 3.48%.
1
0.285, CHCl3); H NMR (300 MHz, CDCl3): l 1.42
(d, J=6.9 Hz, 3H), 1.92 (s, 3H), 4.41 (q, J=6.6 Hz,
1H), 7.00–7.09 (m, 4H), 7.12–7.53 (m, 16H), 7.59–7.73
(m, 6H), 9.69 (d, J=8.6 Hz, 1H); 31P NMR (121.46
MHz, CDCl3): l −14.5; IR (KBr pellet): w 3055 (w),
2966 (w), 1598 (w), 1585 (w), 1491 (m), 1432 (s), 1050
(m), 1028 (s), 818 (s), 739 (vs), 697 (vs); EIMS (m/z):
535 ([M]+, 0.4%). Anal. calcd for C38H34NP: C, 85.21;
H, 6.40; N, 2.61. Found: C, 84.90; H, 6.51; N, 2.49%.
4.8. {(R)-[2-(Di-p-tolylphosphanyl)naphthalen-1-
yl]phenylmethyl}methyl((1%R)-1%-phenylethyl)amine,
(R,R)-3b
Following the same procedure for the preparation of
(R,R)-3a, reduction of (R,R)-6b afforded (R,R)-3b as
amorphous white solids (yield, 30%): [h]2D0=+161 (c
0.19, CHCl3); 1H NMR (300 MHz, CDCl3): l 1.42
(d, J=6.9 Hz, 3H), 1.89 (s, 3H), 2.34 (s, 3H), 2.36 (s,
3H), 4.41 (q, J=6.6 Hz, 1H), 6.99–7.29 (m, 14H),
7.36–7.70 (m, 10H), 9.22 (d, J=8.6 Hz, 1H); 31P
NMR (121.46 MHz, CDCl3): l −16.2; IR (KBr pel-
let): w 2970 (w), 1599 (m), 1495 (s), 1448 (m), 1186
(m), 1028 (m), 806 (vs), 746 (m), 699 (vs); EIMS
(m/z): 563 ([M]+, 2%); ESIMS (m/z): 564.3 ([M+1]+,
100%); HRMS (EI) calcd for C40H38NP: 563.2742.
Found: 563.2728.
4.11. 1-{(R)-[Acetyl((1%R)-1%-phenylethyl)amino]-
phenylmethyl}naphthalen-2-yl trifluoromethanesulfonate,
(R,R)-9
Following the same procedure for the preparation of
(R,R)-5, the reaction of (R,R)-8 and Tf2O afforded
(R,R)-9 (yield, 93%): mp 148–150°C; [h]2D0=+81.7 (c
0.61, CHCl3); 1H NMR (300 MHz, CDCl3): l 1.98
(d, J=7.3 Hz, 3H), 1.99–2.22 (m, 3H), 4.43 (brs, 1H),
6.63 (brs, 2H), 6.90–7.47 (m, 13H), 7.77–7.80 (m,
2H); IR (KBr pellet): w 3061 (w), 3022 (w), 1658 (vs),
1601 (w), 1512 (m), 1493 (m), 1447 (m), 1423 (vs),
1415 (vs), 1303 (s), 1214 (vs), 1140 (s), 952 (vs), 763
(s), 612 (s); EIMS (m/z): 422 ([M−105]+, 43%). Anal.
calcd for C28H24F3NO4S: C, 63.75; H, 4.59; N, 2.66.
Found: C, 63.61; H, 4.45; N, 2.66%.
4.9. 1-{(R)-[Acetyl((1%R)-1%-phenylethyl)amino]-
phenylmethyl}naphthalen-2-yl acetate, (R,R)-7
Acetyl chloride (1.8 mL, 25.05 mmol) was slowly
added to a solution of amino naphthol (R,R)-1 (2.949
g, 8.35 mmol) in dry pyridine (42 mL) at 0°C, and
the mixture was stirred at room temperature for 12 h.
Then reaction was quenched with water. The solvent
was removed under reduced pressure, and the result-
ing residue was diluted with ethyl acetate, washed
with water, 1N aqueous HCl, saturated aqueous
NaHCO3, and brine. The organic phase was dried
over Na2SO4, and concentrated again under reduced
pressure. The resulting residue was submitted to chro-
matographic separation on silica gel with hexane/
EtOAc (2:1) as eluent to give (R,R)-7 as a white solid
(3.091 g, 85%): mp 133–135°C; [h]2D0=+73.4 (c 0.42,
CHCl3); 1H NMR (300 MHz, CDCl3): l 1.60–1.68
(m, 3H), 1.93–2.04 (m, 5H), 2.28 (brs, 1H), 4.58 (brs,
1H), 5.04 (m, 1H), 6.71–6.91 (m, 5H), 7.17–7.78 (m,
10H), 8.30 (brs, 1H); IR (KBr pellet): w 3055 (w),
1766 (vs), 1622 (vs), 1496 (m), 1428 (m), 1366 (m),
1312 (m), 1274 (m), 1191 (vs), 1016 (s), 809 (s), 737
(s), 699 (s); EIMS (m/z): 437 ([M]+, 0.5%). Anal.
calcd for C29H27NO3: C, 79.61; H, 6.22; N, 3.20.
Found: C, 79.17; H, 6.44; N, 3.09%.
4.12. N-{(R)-[2-(Diphenylphosphinoyl)naphthalen-1-
yl]phenylmethyl}-N-((1%R)-1%-phenylethyl)acetamide,
(R,R)-10a
Following the same procedure for the preparation of
(R,R)-6a, the coupling reaction of (R,R)-9 with
H(O)PPh2 afforded (R,R)-10a (yield, 64%): mp 274.5–
275.5°C; [h]2D0=+233.5 (c 0.56, CHCl3); 1H NMR
(300 MHz, CDCl3): l 2.02 (d, J=6.1 Hz, 3H), 2.29
(s, 3H), 4.60–4.62 (m, 1H), 6.14 (s, 1H), 6.85–6.87 (m,
1H), 7.02–7.22 (m, 8H), 7.25–7.78 (m, 16H), 8.23–8.24
(m, 1H); 31P NMR (121.46 MHz, CDCl3): l 34.1; IR
(KBr pellet): w 3053 (w), 2975 (w), 1646 (vs), 1438 (s),
1413 (s), 1292 (vs), 1187 (vs), 1115 (s), 761 (s), 736
(m), 724 (m), 696 (vs); EIMS (m/z): 474 ([M−105]+,
46%). Anal. calcd for C39H34NO2P: C, 80.81; H, 5.91;
N, 2.42. Found: C, 80.48; H, 5.96; N, 2.36%.

1296
Y. Wang et al. / Tetrahedron: Asymmetry 13 (2002) 1291–1297
4.13.
N-{(R)-[2-(Di-p-tolylphosphinoyl)naphthalen-1-
4.16. {(R)-[2-(Diphenylphosphanyl)naphthalen-1-
yl]phenylmethyl}-N-((1%R)-1%-phenylethyl)acetamide,
(R,R)-10b
yl]phenylmethyl}ethyl((1%R)-1%-phenylethyl)amine, (R,R)-
3c
Following the same procedure for the preparation of
(R,R)-6b, the coupling reaction of (R,R)-9 with di(4-
toly)phosphine oxide afforded (R,R)-10b (yield, 61%):
mp 244–245°C; [h]D20=+203.2 (c 0.57, CHCl3); 1H NMR
(300 MHz, CDCl3): l 2.02 (d, J=6.1 Hz, 3H), 2.30 (s,
3H), 2.39 (s, 3H), 2.44 (s, 3H), 4.58–4.60 (m, 1H), 6.15
(s, 1H), 6.85 (m, 1H), 7.04–7.28 (m, 12H), 7.38–7.43 (m,
2H), 7.52–7.58 (m, 4H), 7.70–7.77 (m, 4H), 8.25–8.26 (m,
1H); 31P NMR (121.46 MHz, CDCl3): l 34.2; IR (KBr
pellet): w 1658 (vs), 1600 (s), 1492 (m), 1420 (m), 1296 (s),
1181 (s), 1114 (s), 1098 (m), 809 (s), 758 (s), 698 (s), 663
(vs); EIMS (m/z): 502 ([M−105]+, 18%). Anal. calcd for
C41H38NO2P·0.5H2O: C, 79.85; H, 6.37; N, 2.27. Found:
C, 80.23; H, 6.45; N, 2.32%.
Following the same procedure for the preparation of
(R,R)-3a, the reduction of (R,R)-11a afforded (R,R)-3c
1
(yield, 51%): [h]2D0=−25.9 (c 0.525, CHCl3); H NMR
(300 MHz, CDCl3): l 0.57 (t, J=7.3 Hz, 3H), 1.49 (d,
J=6.7 Hz, 3H), 2.51–2.60 (m, 1H), 2.66–2.75 (m, 1H),
4.39 (q, J=6.7 Hz, 1H), 6.93–6.97 (m, 3H), 7.07–7.39 (m,
14H), 7.45–7.62 (m, 8H), 7.71 (d, J=8.6 Hz, 1H), 10.05
(d, J=9.2 Hz, 1H); 31P NMR (121.46 MHz, CDCl3): l
−14.4; IR (KBr pellet): w 3053 (w), 2967 (w), 1598 (w),
1584 (m), 1493 (m), 1450 (m), 1433 (s), 1180 (m), 1027
(m), 818 (s), 742 (vs), 696 (vs); EIMS (m/z): 549 ([M]+,
0.3%); ESIMS (m/z): 550.3 ([M+1]+, 100%); HRMS (EI)
calcd for C39H36NP: 549.2585. Found: 549.2583.
4.17. {(R)-[2-(Di-p-tolylphosphanyl)naphthalen-1-
4.14. {(R)-[2-(Diphenylphosphinoyl)naphthalen-1-
yl]phenylmethyl}ethyl((1%R)-1%-phenylethyl)amine, (R,R)-
11a
yl]phenylmethyl}ethyl((1%R)-1%-phenylethyl)amine, (R,R)-
3b
Following the same procedure for the preparation of
(R,R)-3a, the reduction of (R,R)-11b afforded (R,R)-3d
(yield, 56%): [h]2D0=+8.4 (c 0.515, CHCl3); 1H NMR (300
MHz, CDCl3): l 0.55 (t, J=7.2 Hz, 3H), 1.50 (d, J=6.9
Hz, 3H), 2.32 (s, 3H), 2.36 (s, 3H), 2.51–2.58 (m, 1H),
2.67–2.74 (m, 1H), 4.41 (q, J=6.9 Hz, 1H), 6.95–7.01 (m,
7H), 7.02–7.36 (m, 9H), 7.44–7.63 (m, 7H), 7.70–7.72 (m,
1H), 10.02 (d, J=8.6 Hz, 1H); 31P NMR (121.46 MHz,
CDCl3): l −16.2; IR (KBr pellet): w 3057 (w), 3027 (w),
2968 (m), 2920 (m), 1598 (m), 1495 (vs), 1449 (s), 1395
(m), 1375 (m), 1185 (m), 1089 (m), 1029 (m), 805 (vs),
699 (vs); EIMS (m/z): 577 ([M]+, 0.9%); ESIMS (m/z):
578.3 ([M+1]+, 100%); HRMS (EI) calcd for C41H40NP:
577.2898. Found: 577.2891.
To a solution of (R,R)-10a (552 mg, 0.953 mmol) in dried
THF (25 mL), was added BH3·Me2S (0.33 mL, 3.43
mmol) at 0°C. The reaction mixture was heated to reflux,
and stirred for additional 18 h. After cooling to room
temperature, the reaction was carefully quenched with
saturated aqueous NH4Cl and the mixture was extracted
with ethyl acetate. The organic phase was washed with
water, brine, dried over Na2SO4, and then concentrated
under reduced pressure. The residue was submitted to
chromatographic separation on silica gel with hexane/
EtOAc (4:1) as eluent to give a white amorphous solid
(509 mg, 95%): [h]D20=+57.9 (c 0.535, CHCl3); 1H NMR
(300 MHz, CDCl3): l 0.39 (t, J=7.0 Hz, 3H), 1.48 (d,
J=6.8 Hz, 3H), 2.46–2.62 (m, 2H), 4.39 (q, J=6.2 Hz,
1H), 6.90–7.00 (m, 4H), 7.08–7.73 (m, 22H), 10.23 (d,
J=8.8 Hz, 1H); 31P NMR (121.46 MHz, CDCl3): l 35.5;
IR (KBr pellet): w 3057 (w), 1598 (w), 1494 (m), 1437 (s),
1182 (s), 1115 (s), 818 (m), 750 (s), 721 (s), 698 (vs); EIMS
(m/z): 460 ([M−105]+, 79%). Anal. calcd for C39H36NOP:
C, 82.81; H, 6.41; N, 2.48. Found: C, 82.39; H, 6.71; N,
2.48%.
4.18. Typical procedure for Pd(0)-catalyzed asymmetric
allylic alkylation reaction
In a Schlenk tube containing 1,3-dipheylprop-2-en-1-yl
acetate ( )-12 (57 mg, 0.227 mmol), [Pd(C3H5)Cl]2 (2.1
mg, 0.0568 mmol, 2.5 mol%), (R,R)-3a (7.3 mg, 0.136
mmol, 6 mmol%), Cs2CO3 (148 mg, 0.45 mmol) was
added ClCH2CH2Cl (2 mL). The mixture was stirred at
room temperature for 20 min, and dimethyl malonate
(59.4 mg, 0.45 mmol) was then added. The reaction
mixture was allowed to stir at room temperature for 24
h. The reaction was quenched with saturated aqueous
NH4Cl, extracted with EtOAc (3×20 mL). The organic
phase was washed with saturated aqueous NaHCO3,
water, and brine, dried over Na2SO4, and concentrated
under reduced pressure. The residue was purified by
flash chromatography on silica gel with hexane/EtOAc
(4:1) as eluent to produce (S)-13 (73 mg, 99%) as a
colorless oil with 72.2% ee. 1H NMR (300 MHz,
CDCl3): l 3.52 (s, 3H), 3.69 (s, 3H), 3.97 (d, J=10.9
Hz, 1H), 4.27 (dd, J=10.9, 8.7 Hz, 1H), 6.34 (dd,
J=15.4, 8.4 Hz, 1H), 6.48 (d, J=15.8 Hz, 1H), 7.17–
7.24 (m, 10H). The enantiomeric excess was determined
by HPLC (Chiralpak AD, flow rate=1 mL/min, hex-
ane:iso-propanol=90:10, tR=12.6 min, tS=18.9 min).
4.15. {(R)-[2-(Di-p-tolylphosphinoyl)naphthalen-1-
yl]phenylmethyl}ethyl((1%R)-1%-phenylethyl)amine, (R,R)-
11b
Following the same procedure for the preparation of
(R,R)-11a, the reduction of (R,R)-10b afforded (R,R)-
11b (yield, 70%): [h]D20=+66.9 (c 0.495, CHCl3); 1H NMR
(300 MHz, CDCl3): l 0.38 (t, J=7.3 Hz, 3H), 1.49 (d,
J=6.7 Hz, 3H), 2.39 (s, 3H), 2.41 (s, 3H), 2.49–2.64 (m,
2H), 4.39 (q, J=6.1 Hz, 1H), 6.93–6.99 (m, 3H), 7.09–
7.36 (m, 8H), 7.45–7.64 (m, 8H), 7.67–7.72 (m, 5H), 10.21
(d, J=8.6 Hz, 1H); 31P NMR (121.46 MHz, CDCl3): l
35.5; IR (KBr pellet): w 1600 (m), 1494 (m), 1449 (m),
1398 (w), 1182 (vs), 1113 (vs), 1098 (s), 809 (s), 700 (s),
657 (s); EIMS (m/z): 488 ([M−105]+, 100%). Anal. calcd
for C41H40NOP: C, 82.94; H, 6.79; N, 2.36. Found: C,
82.46; H, 7.28; N, 2.37%.

Y. Wang et al. / Tetrahedron: Asymmetry 13 (2002) 1291–1297
1297
Acknowledgements
M.; Buchwald, S. L. Org. Lett. 2001, 3, 1897; (j) Hamada,
T.; Chieffi, A.; Ahman, J.; Buchwald, S. L. J. Am. Chem.
Soc. 2002, 124, 1261; (k) Wang, Y.; Li, X.; Ding, K.
Tetrahedron Lett. 2002, 43, 159.
Financial support from the National Natural Science
Foundation of China, the Chinese Academy of Sci-
ences, the Major Basic Research Development Program
of China (Grant No. G2000077506) and the Science
and Technology Commission of Shanghai Municipality
are gratefully acknowledged.
3. Cimarelli, C.; Mazzanti, A.; Palmieri, G.; Volpini, E. J.
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