Palladium-catalyzed asymmetric allylic alkylation using chiral aminophosphine ligands

Article abstract of DOI:10.1016/S0957-4166(01)00310-X

Palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate 18 with a dimethyl malonate-BSA-LiOAc system has been successfully carried out in the presence of new chiral aminophosphine ligands 1-5 in good yields with good enantioselectivities (up to 85% e.e.).

Full text of DOI:10.1016/S0957-4166(01)00310-X

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 1677–1682
Palladium-catalyzed asymmetric allylic alkylation using chiral
aminophosphine ligands
Takashi Mino,* Yoh-ichi Tanaka, Koji Akita, Kouhei Anada, Masami Sakamoto and
Tsutomu Fujita
Department of Materials Technology, Faculty of Engineering, Chiba University, Inage-ku, Chiba 263-8522, Japan
Received 22 February 2001; accepted 5 April 2001
Abstract—Palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate 18 with a dimethyl malonate–
BSA–LiOAc system has been successfully carried out in the presence of new chiral aminophosphine ligands 1–5 in good yields
with good enantioselectivities (up to 85% e.e.). © 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Palladium-catalyzed allylic alkylation is a widely used
process in organic synthesis,1 and the development of
efficient enantioselective catalysis for this reaction is
awaited.2 Recently, P,N-bidentate ligands were found
to be efficient chirality sources for this reaction.3 Exam-
ples of such aminophosphine ligands are 4-[2-(diphenyl-
phosphino)phenyl]-4,5-dihydro-3H-dinaphth[2,1-c:1%,2%-
e]azepine,4 1-[2%-(diphenylphosphino)-1%-naphthalenyl]-
2-methylpyrrolidine5 and 1-[2%-(diphenylphosphino)-
phenyl]-2-(benzyloxymethyl)pyrrolidine.6 We have pre-
viously reported phosphine–hydrazone bidentate lig-
ands such as 2-diphenylphosphinobenzaldehyde SAMP
hydrazone (DPPBA–SAMP).7
2.1. Preparation of aminophosphine ligands
The synthesis of the chiral aminophosphine ligands
(such as (R)-1-[2-(diphenylphosphino)phenyl]-2-(meth-
oxymethyl)pyrrolidine (R)-1) is shown in Scheme 1.
Nucleophilic aromatic substitution (SNAr) reactions9 of
the corresponding phosphine oxide such as diphenyl(2-
methoxyphenyl)phosphine oxide 6 with lithiated (R)-1-
(methoxymethyl)pyrrolidine (R)-9 gave the corres-
ponding aminophosphine oxide 10. The resulting
aminophosphine oxide 10 was converted into the
desired homochiral aminophosphine ligand (R)-1 in
good yield by reduction with trichlorosilane–triethyl-
amine. Aminophosphine ligands (R)-210 and (R)-5
were prepared in the same manner using the corre-
sponding phosphine oxides 1-methoxy-2-diphenylphos-
phinonaphthalene oxide 711 and 9-methoxy-10-
diphenylphosphinophenanthrene oxide 8.
We were interested in aminophosphine ligands which
have an ether bond such as a methoxymethyl group.
This ether bond was expected to interact with the
incoming nucleophile to bring about good stereoselec-
tivity.8 We designed a DPPBA–SAMP-derived chiral
aminophosphine without a hydrazone moiety for appli-
cation in asymmetric catalysis. Herein, we report palla-
dium-catalyzed asymmetric allylic alkylation using
chiral aminophosphine ligands 1–5 which were pre-
pared from homochiral 2-methoxymethylpyrrolidine9
and its derivatives.
Aminophosphine ligand (S)-3 was prepared in the same
manner using (S)-2-methoxyethoxymethylpyrrolidine
(S)-1312 (Scheme 2). This ligand has a methoxyethoxy-
methyl moiety attached to the pyrrolidine back-
bone.
* Corresponding author. Tel.: +81 43 290 3385; fax: +81 43 290 3401; e-mail: tmino@planet.tc.chiba-u.ac.jp
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00310-X

1678
T. Mino et al. / Tetrahedron: Asymmetry 12 (2001) 1677–1682
Scheme 1.
Scheme 2.
ture of N,O-bis(trimethylsilyl)acetamide (BSA) and 2
mol% of LiOAc in THF) (Scheme 4, Table 1).
The synthesis of chiral aminophosphine ligand (S)-4 is
shown in Scheme 3. An aminoalcohol phosphine (S)-17
was prepared in the same manner using
L-prolinol
Using ligand (R)-1, the product 20 was obtained in
excellent yield (93%), but the enantiomeric excess was
low (39% e.e.) (entry 1). However, using ligand (R)-2
which has a naphthyl backbone, the product 20 was
obtained with higher enantioselectivity (74% e.e.) (entry
3). When the reaction was carried out using (R)-2 in
toluene, the yield increased from 92 to 94% and the e.e.
increased from 74 to 76% (entry 3 versus 4). Complet-
ing the reaction at −20°C further improved the enan-
tioselectivity to 83% e.e. (entry 9). When the reaction
was carried out using ligand (S)-3 instead of (R)-2 in
THF, the yield and the e.e. increased slightly (entry 3
versus 10). Indicating that a methoxyethoxymethyl
group of the pyrrolidine side chain in ligand (S)-4
interacts slightly with the incoming nucleophile.
(S)-15 and phosphine oxide 7. The ligand (S)-4 was
prepared by alkylation of the hydroxyl group in (S)-17
with 1-bromo-2-(methoxyethoxy)ethane. This ligand
has a methoxyethoxyethoxymethyl moiety attached to
the pyrrolidine backbone.
2.2. Palladium-catalyzed asymmetric allylic alkylation
The chiral aminophosphine ligands 1–5 were used as
catalysts in the palladium-catalyzed asymmetric allylic
alkylation of 1,3-diphenyl-2-propenyl acetate 18 with
dimethyl malonate 19.13 This reaction was carried out
under our previously reported conditions7 (2 mol% of
[Pd(h3-C3H5)Cl]2, 4 mol% of chiral ligand, and a mix-
Scheme 3.

T. Mino et al. / Tetrahedron: Asymmetry 12 (2001) 1677–1682
1679
Scheme 4.
Table 1. Asymmetric allylic alkylation catalyzed by palladium complexes with ligands 1–5
Entry
Ligand
Solv.
Temp. (°C)
Yield (%)a
E.e. (%)b
Conf. of 20c
1
2
3
4
5
6
7
(R)-1
(R)-1
(R)-2
(R)-2
(R)-2
(R)-2
(R)-2
(R)-2
(R)-2
(S)-3
(S)-3
(S)-3
(S)-3
(S)-4
(R)-5
THF
PhMe
THF
rt
rt
rt
rt
rt
rt
rt
0
−20
rt
rt
rt
−20
rt
93
97
92
94
94
95
95
99
88
96
93
97
22
86
95
39
40
74
76
60
64
64
79
83
79
76
79
85
76
57
R
R
R
R
R
R
R
R
R
S
PhMe
MeCN
CH2Cl2
DMF
PhMe
PhMe
THF
PhMe
Ether
THF
8d
9e
10
11
12
13e
14
15
S
S
S
S
PhMe
PhMe
rt
R
a Isolated yields.
b Determined by HPLC analysis using a chiral column (Chiralcel OD).
c Determined by optical rotation.
d This reaction was carried out for 96 h.
e This reaction was carried out for 7 days.
Although the enantioselectivity was improved to 85%
e.e. by further decreasing the temperature (−20°C), the
reaction rate reduced (entry 13). Using (S)-4 as a
ligand, the yield was decreased slightly without a
decrease in enantioselectivity (entry 11 versus 14).
Using ligand (R)-5 which has a phenanthrenyl back-
bone instead of a naphthyl backbone, the e.e. decreased
from 76 to 57% (entry 4 versus 15).
catalyst in the p-allyl system as designated in 21b,
affording 20.
3. Conclusion
We showed the palladium-catalyzed asymmetric allylic
alkylation of 1,3-diphenyl-2-propenyl acetate 18 with
dimethyl malonate 19 using chiral aminophosphine lig-
ands 1–5 with good e.e.
2.3. The mechanism for asymmetric induction with chi-
ral aminophosphine ligands
4. Experimental
The mechanism for asymmetric induction with this type
of ligand is rationalized on the basis of the stereochem-
ical results obtained. The (R)-1-(methoxymethyl)-
pyrrolidine derived ligand (R)-2 would provide a five-
membered chelate by coordination of the rather more
electron-donating nitrogen group and phosphorus
group to the palladium catalyst.14 In the conforma-
tional equilibrium of sterically favored p-allylpalladium
complexes 21a and 21b, complex 21b would be formed
preferentially because of greater steric interference
between the methoxymethyl group of the ligand and the
allylic compound in 21a (Scheme 5).5,15 This interfer-
ence was more effective than the case of methyl group
and benzyloxymethyl group. Therefore, the nucleophile
would attack the allylic terminus in 21b trans to the
better p-acceptor, which is the phosphine group in the
present case, from the back side of the palladium
4.1. General methods
Melting points were measured on a Shibata micromelt-
ing point apparatus. NMR spectra were recorded on a
JEOL LA-400 system or a Bruker DPX-300 system
with TMS as an internal standard. Mass spectra were
recorded on a JEOL JMS-HX110. Optical rotations
were measured on a JASCO DIP-370.
4.2. Synthesis of 9-methoxy-10-diphenylphos-
phinophenanthrene 8
To a mixture of 9-methoxyphenanthrene (0.313 g, 1.5
mmol), TMEDA (0.23 mL, 1.52 mmol) and ether (4
mL) was added dropwise n-BuLi in hexane (1.56 M, 1.5
mL, 2.3 mmol) over 10 min and the mixture was stirred
at rt for 2 h. Chlorodiphenylphosphine (0.27 mL, 1.5

1680
T. Mino et al. / Tetrahedron: Asymmetry 12 (2001) 1677–1682
Scheme 5.
mmol) was added and the resulting mixture was stirred
for a further 2 h. Then it was diluted with ether and
quenched with aq. HCl (2 M, 30 mL). The organic
layer was washed with aq. Na2CO3 (2 M, 30 mL),
brine, dried over MgSO4, and concentrated under
reduced pressure. The residue was dissolved in AcOH
(7.5 mL) and aq. H2O2 (30%, 0.25 mL) was added. The
mixture was gradually heated to 80°C over 20, and
stirred at 80°C for 2 h. After being cooled to rt, the
mixture was diluted with benzene (15 mL) and added
2 M aq. NaOH (40 mL) at 0°C. The water layer was
extracted with ether and the combined extracts were
washed with water, dried over MgSO4, and concen-
trated under reduced pressure. The residue was purified
by silica-gel chromatography (elution with n-hexane/
EtOAc=1/3) (0.507 g, 1.24 mmol, 83%); mp 142–
4.3.1. (R)-1-[2%-(Diphenylphosphinyl)phenyl]-2-(methoxy-
methyl)pyrrolidine (R)-10. Yield 68%; mp 49–50°C;
[h]2D5=−71 (c 0.10, CHCl3); 1H NMR (400 MHz,
CDCl3): l 1.39–1.50 (m, 2H), 1.61–1.69 (m, 1H), 1.77–
1.94 (m, 1H), 2.63 (t, J=8.9 Hz, 1H), 2.72 (q, J=7.1
Hz, 1H), 3.03 (dd, J=3.7 and 9.2 Hz, 1H), 3.12 (s, 3H),
3.45–3.56 (m, 1H), 3.63–3.77 (m, 1H), 6.81 (dq, J=1.3
and 3.8 Hz, 1H), 6.94 (t, J=7.4 Hz, 1H), 7.18–7.39 (m,
12H); 13C NMR (75 MHz, CDCl3); 23.66, 29.02, 56.28,
58.73, 60.70, 74.65, 122.21, 128.06–133.20 (m, Ar),
135.47, 154.42; 31P NMR (121 MHz, CDCl3): l 27.24;
FAB-MS (m/z) 392 (M++H, 64); HRMS (FAB) calcd
for C24H27NO2P (M++H) 392.1779, found 392.1742.
4.3.2. (R)-1-[2%-(Diphenylphosphinyl)-1%-naphthalenyl]-2-
(methoxymethyl)pyrrolidine (R)-11. Yield 85%; mp 106–
108°C; [h]2D5=−244 (c 0.11, CHCl3); 1H NMR (300
MHz, CDCl3): l 1.56 (br, 1H), 1.73–1.88 (m, 2H),
2.03–2.22 (br, 1H), 2.77 (br, 1H), 3.02 (s, 3H), 3.03–
3.10 (m, 2H), 3.23 (br-s, 1H), 4.30 (br-s, 1H), 7.17 (dd,
J=8.6 and 12.6 Hz, 1H), 7.40–7.62 (m, 9H), 7.68–7.81
(m, 4H), 7.86 (d, J=7.8 Hz, 1H), 8.11–8.14 (br, 1H);
13C NMR (75 MHz, CDCl3): l 25.11, 29.88, 53.88,
58.93, 63.99, 76.12, 125.87, 126.35, 128.09, 128.55–
135.95 (m, Ar), 137.44, 152.34; 31P NMR (121 MHz,
CDCl3): l 26.49; FAB-MS (m/z) 442 (M++H, 100);
HRMS (FAB) calcd for C28H29NO2P (M++H)
442.1936, found 442.1934.
1
143°C; H NMR (300 MHz, CDCl3): l 3.21 (s, 3H),
7.38–7.82 (m, 14H), 8.08 (d, J=8.1 Hz, 1H), 8.64 (d,
J=8.3 Hz, 1H), 8.71 (d, J=8.3 Hz, 1H), 9.00 (d, J=8.4
Hz, 1H); 13C NMR (75 MHz, CDCl3): l 63.46, 116.38,
117.71, 123.02–132.69 (m, Ar), 134.87 (d, J=1.7 Hz),
135.57, 136.99; 31P NMR (121 MHz, CDCl3): l 29.19;
FAB-MS (m/z) 409 (M++H, 100); HRMS (FAB) calcd
for C27H22O2P (M++H) 409.1357, found 409.1371.
4.3. Synthesis of aminophosphine oxide: general
procedure
To a solution of amine (1.03 mmol) in THF (1 mL) at
−80°C was added slowly n-BuLi in hexane (0.71 mL,
1.1 mmol, 1.56 M) at −80°C over 10 min. The mixture
was allowed to warm to rt and stirred for 2 h. The
phosphine oxide (1.0 mmol) was added at 0°C, and the
mixture stirred for a further 20 h at rt. The mixture was
diluted with ether and quenched with satd NH4Cl. The
organic layer was washed with brine, dried over
MgSO4, and concentrated under reduced pressure. The
residue was purified by silica-gel chromatography.
4.3.3. (R)-1-[10%-(Diphenylphosphinyl)-9%-phenanthrenyl]-
2-(methoxymethyl)pyrrolidine (R)-12. Yield 83%; mp
101–102°C; [h]D25=−224 (c 0.135, CHCl3); 1H NMR
(300 MHz, CDCl3): l 1.28 (br, 1H), 1.65–1.77 (br-m,
2H), 1.98 (br-s, 1H), 2.60 (br, 1H), 2.98 (s, 3H), 3.13–
3.24 (m, 2H), 3.43 (br-s, 1H), 4.39 (br-s, 1H), 7.04–7.13
(m, 1H), 7.27–7.47 (m, 7H), 7.54–7.78 (m, 6H), 7.98 (d,
J=8.5 Hz, 1H), 8.11 (d, J=8.3 Hz, 1H), 8.55 (d, J=8.3

T. Mino et al. / Tetrahedron: Asymmetry 12 (2001) 1677–1682
1681
Hz, 1H), 8.72 (d, J=8.3 Hz, 1H); 13C NMR (75 MHz,
CDCl3): l 24.53, 29.31, 52.84, 59.00, 65.08, 75.46, 122.74,
123.73, 125.74, 126.13, 126.59, 126.45, 128.43–134.64 (m,
Ar), 137.02, 138.40, 151.83; 31P NMR (121 MHz,
CDCl3): l 26.46; FAB-MS (m/z) 492 (M++H, 86);
HRMS (FAB) calcd for C32H31NO2P (M++H) 492.2092,
found 492.2072.
4.5.1. (R)-1-[2%-(Diphenylphosphino)phenyl]-2-(methoxy-
methyl)pyrrolidine (R)-1. Yield 87%; mp 60–62°C;
[h]2D0=+8.2 (c 1.00, CHCl3); 1H NMR (300 MHz,
CDCl3): l 1.54–1.86 (m, 3H), 2.01–2.16 (m, 1H), 2.63 (t,
J=8.9 Hz, 1H), 2.72 (q, J=7.1 Hz, 1H), 3.03 (dd, J=3.7
and 9.2 Hz, 1H), 3.12 (s, 3H), 3.45–3.56 (m, 1H),
3.63–3.77 (m, 1H), 6.81 (dq, J=1.3 and 3.8 Hz, 1H),
6.94 (t, J=7.4 Hz, 1H), 7.18–7.39 (m, 12H); 13C NMR
(75 MHz, CDCl3): l 24.48, 30.23, 56.03 (d, J=8.4 Hz),
59.27, 60.92 (d, J=2.5 Hz), 75.82, 121.62 (d, J=2.8 Hz),
123.92, 128.53–134.85 (m, Ar), 135.45 (d, J=10.9 Hz),
138.16 (d, J=12.6 Hz), 138.56 (d, J=11.9 Hz), 153.99
(d, J=19.6 Hz); 31P NMR (121 MHz, CDCl3): l −12.14;
FAB-MS (m/z) 376 (M++H, 64); HRMS (FAB) calcd
for C24H27NOP (M++H) 376.1830, found 376.1813.
4.3.4. (S)-1-[2%-(Diphenylphosphinyl)-1%-naphthalenyl]-2-
[(2¦-methoxyethoxy)methyl]pyrrolidine (S)-14. Yield
33%; mp 94–95°C; [h]2D5=+206 (c 1.0, CHCl3); 1H NMR
(300 MHz, CDCl3): l 1.43–1.90 (m, 3H), 2.17–2.24 (m,
2H), 2.84–3.29 (m, 7H), 3.24 (s, 3H), 4.29 (br, 1H), 7.17
(dd, J=8.6 and 12.6 Hz, 1H), 7.40–7.61 (m, 9H),
7.70–7.88 (m, 5H), 8.12 (br, 1H); 13C NMR (75 MHz,
CDCl3): l 24.67, 29.55, 54.04, 58.91, 63.45, 69.94, 71.73,
74.14, 125.94, 127.65, 128.14–135.49 (m, Ar), 137.04,
152.08; 31P NMR (121 MHz, CDCl3): l 26.61; FAB-MS
(m/z) 486 (M++H, 8); HRMS (FAB) calcd for
C30H33NO3P (M++H) 486.2198, found 486.2160.
4.5.2. (R)-1-[2%-(Diphenylphosphino)-1%-naphthalenyl]-2-
(methoxymethyl)pyrrolidine (R)-2. Yield 100%; mp 105–
106°C; [h]2D0=−12.3 (c 1.0, CHCl3); 1H NMR (300 MHz,
CDCl3): l 2.00 (br, 3H), 2.39 (br, 1H), 2.89 (br, 1H), 3.09
(s, 3H), 3.22 (br, 3H), 4.08 (br, 1H), 7.06 (br, 1H),
7.14–7.38 (m, 11H), 7.47 (br, 2H), 7.60 (d, J=8.5 Hz,
1H), 7.85 (br, 1H); 13C NMR (75 MHz, CDCl3): l 25.05,
30.11, 54.32, 58.59 (d, J=12.4 Hz), 63.09, 123.85,
124.85, 125.78–133.81 (m, Ar), 135.56, 138.55, 139.08;
31P NMR (121 MHz, CDCl3): l −16.22; FAB-MS (m/z)
426 (M++H, 57); HRMS (FAB) calcd for C28H29NOP
(M++H) 426.1987, found 426.1976.
4.4. Synthesis of (S)-1-[2%-(diphenylphosphinyl)-1%-naph-
thalenyl]-2-(hydroxymethyl)pyrrolidine (S)-16
To a solution of -prolinol (S)-15 (0.104 g, 1.03 mmol)
L
in THF (1 mL) at −80°C was added slowly n-BuLi in
hexane (1.56 M, 1.41 mL, 2.2 mmol) over 10 min, and
the mixture was stirred at rt for 2 h. Phosphine oxide 7
(0.359 g, 1.0 mmol) was added at 0°C and stirring was
continued for 20 h at rt. The mixture was diluted with
ether and quenched with satd NH4Cl. The organic layer
was washed with brine, dried over MgSO4, and concen-
trated under reduced pressure. The residue was purified
by silica-gel chromatography (elution with n-hexane/ace-
tone/EtOAc=10/4/1) (75%); mp 218–220°C; [h]2D5=
4.5.3. (S)-1-[2%-(Diphenylphosphino)-1%-naphthalenyl]-2-
[(2¦-methoxyethoxy)methyl]pyrrolidine (S)-3. Yield 85%;
mp 97–98°C; [h]2D5=+125 (c 1.00, CHCl3); 1H NMR (300
MHz, CDCl3): l 1.99–2.09 (m, 3H), 2.26–2.38 (m, 1H),
2.83 (br, 1H), 3.10–3.31 (m, 7H), 3.26 (s, 3H), 4.08 (br-s,
1H), 7.04 (br-s, 1H), 7.29 (br, 10H), 7.43–7.46 (m, 2H),
7.60 (d, J=8.5 Hz, 1H) 7.83 (br, 2H); 13C NMR (75
MHz, CDCl3): l 25.02, 30.19, 54.29, 58.94, 62.98, 70.12,
71.72, 75.07, 124.05, 125.74, 126.02–133.85 (m, Ar),
135.88, 138.50; 31P NMR (121 MHz, CDCl3): l −16.31;
FAB-MS (m/z) 470 (M++H, 0.4); HRMS (FAB) calcd
for C30H33NO2P (M++H) 470.2249, found 470.2210.
1
+12.5 (c 1.0, CHCl3); H NMR (300 MHz, CDCl3): l
1.59–1.85 (m, 4H), 2.12–2.19 (m, 2H), 3.00–3.08 (m, 1H),
3.30–3.39 (m, 1H), 3.63 (dd, J=4.5 and 12.3 Hz, 1H),
3.95 (br, 1H), 6.75–6.79 (br-m, 1H), 7.07 (dd, J=8.6 and
12.7 Hz, 1H), 7.41–7.72 (m, 10H), 7.79–7.86 (m, 2H),
7.93 (d, J=8.0 Hz, 1H), 7.97 (d, J=8.4 Hz, 1H); 13C
NMR (75 MHz, CDCl3): l 26.16, 28.17, 55.08, 63.24,
67.77, 124.77, 125.96, 126.35, 127.67, 128.23–132.34 (m,
Ar), 137.82, 153.50; 31P NMR (121 MHz, CDCl3): l
27.28; FAB-MS (m/z) 428 (M++H, 100); HRMS (FAB)
calcd for C27H27NO2P (M++H) 428.1779, found
428.1768.
4.5.4. (R)-1-[10%-(Diphenylphosphino)-9%-phenanthrenyl]-
2-(methoxymethyl)pyrrolidine (R)-5. Yield 66%; mp 70–
1
72°C; [h]2D5=−88 (c 0.25, CHCl3); H NMR (300 MHz,
CDCl3): l 1.99 (br, 1H), 2.12–2.21 (m, 2H), 2.39–2.48
(m, 1H), 2.96 (br-s, 3H), 3.09–3.25 (m, 2H), 3.55–3.73
(m, 2H), 4.05–4.17 (m, 1H), 7.01–7.06 (m, 1H), 7.08–7.54
(m, 11H), 7.55–7.76 (m, 3H), 7.85–8.34 (br-m, 2H), 8.64
(d, J=8.2 Hz, 1H); 13C NMR (75 MHz, CDCl3): l
24.09, 29.70, 55.58, 58.58, 64.98, 122.65, 125.61 (d,
J=9.4 Hz), 126.67, 127.12, 127.88, 128.15–133.17 (m,
Ar), 138.38; 31P NMR (121 MHz, CDCl3): l −17.97;
FAB-MS (m/z) 476 (M++H, 34); HRMS (FAB) calcd
for C32H29NO2P (M+−H) 474.1987, found 474.1955.
4.5. General procedure for reduction of aminophosphine
oxides
To a mixture of phosphine oxide (0.3 mmol), triethyl-
amine (0.34 mL, 1.2 mmol) and m-xylene (2 mL) was
added trichlorosilane (0.24 mL, 1.2 mmol) at 0°C under
an argon atmosphere. The reaction mixture was stirred
under reflux for 6 h. After being cooled to rt, the mixture
was diluted with ether and quenched with 2 M aq.
NaOH. 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).
4.5.5. (S)-1-[2%-(Diphenylphosphino)-1%-naphthalenyl]-2-
(hydroxymethyl)pyrrolidine (S)-17. Yield 66%; mp 183–
184°C; [h]2D5=+206 (c 1.0, CHCl3); 1H NMR (300 MHz,
CDCl3): l 1.87–1.96 (m, 2H), 2.20–2.27 (m, 2H), 2.37–
2.43 (m, 1H), 3.21 (q, J=8.0 Hz, 1H), 3.39 (t, J=11.8
Hz, 1H), 3.72 (d, J=12.0 Hz, 1H), 3.98 (t, J=5.9 Hz,
1H), 4.41 (dt, J=2.9 and 12.5 Hz, 1H), 7.00 (dd,

1682
T. Mino et al. / Tetrahedron: Asymmetry 12 (2001) 1677–1682
J=3.1 and 8.2 Hz, 1H), 7.23–7.38 (m, 10H), 7.45–7.51
(m, 2H), 7.65 (d, J=8.5 Hz, 1H), 7.86–7.91 (m, 2H); 13
NMR (75 MHz, CDCl3): l 25.91, 28.54, 54.55, 63.02,
65.11, 123.70, 125.77, 126.22, 127.14, 128.48–134.50 (m,
Ar), 136.18; 31P NMR (121 MHz, CDCl3): l −17.07;
FAB-MS (m/z) 412 (M++H, 0.4); HRMS (FAB) calcd
for C27H27NOP (M++H) 412.1830, found 412.1833.
References
C
1. (a) Tsuji, J.; Minami, I. Acc. Chem. Res. 1987, 20,
140–145; (b) Trost, B. M.; Verhoeven, T. R. In Compre-
hensive Organometallic Chemistry; Wilkinson, G.; Stone,
F. G. A.; Abel, E. W., Eds.; Pergamon: Oxford, 1982;
Vol. 8, p. 799; (c) Trost, B. M. Acc. Chem. Res. 1980,
13, 385–393.
2. (a) Pfaltz, A.; Lautens, M. In Comprehensive Asymmet-
ric Catalysis; Jacobsen, E. N.; Pfaltz, A.; Yamamoto,
H., Eds.; Springer: Tokyo, 1999; Vol. 2, p. 833; (b)
Trost, B. M.; Van Vranken, D. L. Chem. Rev. 1996, 96,
395–422; (c) Williams, J. M. J. Synlett 1996, 705–710;
(d) Pfaltz, A. Acc. Chem. Res. 1993, 26, 339–345; (e)
Hayashi, T. In Catalytic Asymmetric Synthesis; Ojima,
I., Ed.; VCH: New York, 1993; p. 325; (f) Consiglio, G.;
Waymouth, R. M. Chem. Rev. 1989, 89, 257–276 and
references cited therein.
3. Fache, F.; Schulz, E.; Tommasino, M. L.; Lemaire, M.
Chem. Rev. 2000, 100, 2159–2231 and references cited
therein.
4. (a) Wimmer, P.; Widhalm, M. Monatch. Chem. 1996,
127, 669–681; (b) Wimmer, P.; Widhalm, M. Tetra-
hedron: Asymmetry 1995, 6, 657–660.
5. Hattori, T.; Komuro, Y.; Hashizaka, N.; Takahashi, H.;
Miyano, S. Enantiomer 1997, 2, 203–213.
6. (a) Suzuki, Y.; Abe, I.; Hiroi, K. Heterocycles 1999, 50,
89–94; (b) Hiroi, K.; Suzuki, Y.; Abe, I. Tetrahedron:
Asymmetry 1999, 10, 1173–1188.
7. (a) Mino, T.; Shiotsuki, M.; Yamamoto, N.; Suenaga,
T.; Sakamoto, M.; Fujita, T.; Yamashita, M. J. Org.
Chem. 2001, 66, 1795–1797; (b) Mino, T.; Imiya, W.;
Yamashita, M. Synlett 1997, 583–584.
8. (a) Enders, D. In Asymmetric Synthesis; Morrison, J.
D., Ed.; Academic Press: Orlando, FL, 1984; Vol. 3, p.
275; (b) Hayashi, T.; Yamamoto, A.; Hagihara, T.; Ito,
Y. Tetrahedron Lett. 1986, 27, 191–194.
9. Enders, D.; Klatt, M. Synthesis 1996, 1403–1418.
10. (S)-2 has been synthesized previously. See: Miyano, S.;
Hattori, T.; Komuro, Y.; Kumobayashi, H. Jpn. Kokai
Tokkyo Koho H09241277 (Chem. Abstr. 1997, 127,
302486h).
11. Hattori, T.; Sakamoto, J.; Hayashizaka, N.; Miyano, S.
Synthesis 1994, 199–202.
12. Nakayama, K.; Thompson, W. J. J. Am. Chem. Soc.
1990, 112, 6936–6942.
13. Mino, T.; Tanaka, Y.; Sakamoto, M.; Fujita, T. Hetero-
cycles 2000, 53, 1485–1488.
4.6. Synthesis of (S)-1-[2%-(diphenylphosphino)-1%-naph-
thalenyl]-2-[(2¦-methoxyethoxyethoxy)methyl]pyrrolidine
(S)-4
NaH (60% dispersion in oil, 0.18 mmol, 0.50 g) was
washed with hexane, and DMF (1 mL) was added. To
the suspension of NaH in DMF was added phosphine
9 (0.45 mmol, 9.185 g) at 0°C. The mixture was stirred
for 3 h at rt, treated with methoxyethoxyethyl bromide
(1.87 mmol, 0.25 mL), and stirring was continued for 20
h at rt. The mixture was diluted with ether and quenched
with satd NH4Cl. The organic layer was washed with
brine, dried over MgSO4, and concentrated under reduced
pressure. The residue was purified by silica-gel chro-
matography (elution with n-hexane/EtOAc=6/1) (45%);
mp 60–61°C; [h]2D0=+108 (c 0.102, CHCl3); 1H NMR (300
MHz, CDCl3): l 1.68–2.00 (m, 1H), 1.97 (br-s, 3H), 2.37
(br-s, 1H), 2.82–3.56 (m, 11H), 3.32 (s, 3H), 4.07 (br-s,
1H), 7.04 (br-s, 1H), 7.21–7.37 (m, 10H), 7.43–7.46 (m,
2H), 7.58 (d, J=8.5 Hz, 1H), 7.77–8.32 (m, 2H); 13C NMR
(75 MHz, CDCl3): l 25.04, 30.17, 54.27, 58.98, 63.03,
70.29, 70.40, 71.91, 75.03, 124.63 (d, J=6.6 Hz), 125.63–
138.49 (m, Ar); 31P NMR (121 MHz, CDCl3): l −16.37;
FAB-MS (m/z) 514 (M++H, 42); HRMS (FAB) calcd for
C32H37NO3P (M++H) 514.2511, found 514.2490.
4.7. General procedure for the palladium-catalyzed
allylic alkylation
To a mixture of [Pd(h3-C3H5)Cl]2 (0.01 mmol, 0.004 g),
chiral aminophosphine ligand (0.02 mmol), and LiOAc
(0.01 mmol, 0.001 g) in a solvent (1 mL) was added BSA
(1.5 mmol, 0.37 mL), racemic 1,3-diphenyl-2-propenyl
acetate 18 (0.5 mmol, 0.126 g), and dimethyl malonate
19 (1.5 mmol, 0.17 mL) at rt under an argon atmosphere.
After stirring the mixture for 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 under reduced pressure and the residue was
purified by column chromatography.
14. Ganter, C.; Wagner, T. Chem. Ber. 1995, 128, 1157–
1161.
Acknowledgements
15. Sprinz, J.; Kiefer, M.; Helmchen, G. Tetrahedron Lett.
1994, 35, 1523–1526.
We thank the Ogura group (Chiba University) for
generously sharing their Bruker DPX-300 system.
.