New chiral phosphine-amide ligands in palladium-catalysed asymmetric allylic alkylations

Article abstract of DOI:10.1016/S0957-4166(01)00037-4

Palladium-catalysed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate 8a with a dimethyl malonate-BSA-LiOAc system has been successfully carried out in the presence of new chiral phosphine-amide, such as 5, in good yields and high enantiome

Full text of DOI:10.1016/S0957-4166(01)00037-4

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 287–291
New chiral phosphine–amide ligands in palladium-catalysed
asymmetric allylic alkylations
Takashi Mino,a,* Kohki Kashiharab and Masakazu Yamashitab
aDepartment of Materials Technology, Faculty of Engineering, Chiba University, Inage-ku, Chiba 263-8522, Japan
bDepartment of Molecular Science and Technology, Faculty of Engineering, Doshisha University, Kyotanabe,
Kyoto 610-0394, Japan
Received 18 December 2000; accepted 17 January 2001
Abstract—Palladium-catalysed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate 8a with a dimethyl malonate–
BSA–LiOAc system has been successfully carried out in the presence of new chiral phosphine–amide, such as 5, in good yields and
high enantiomeric excesses of up to 85%. © 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
Trost’s ligand, 1, usually forms P,P-chelate complexes
with Pd.5 However, when the ratio of Pd:1 was raised
(i.e. ]1), P,O-coordination between phosphine and
amide carbonyl was generated.6 More recently, Kim
reported that P,N-bidentate ligand 2 generated P,O-
chelation complexes on the basis of X-ray crystal struc-
ture analysis.7
Palladium-catalysed asymmetric allylic alkylation is a
useful process for asymmetric CꢀC bond-forming reac-
tions. To achieve high enantioselectivity in the catalytic
reaction, a variety of chiral ligands have been studied.1
Recently, P,N-bidentate ligands were found to be
efficient chiral sources for this reaction.2 We previously
reported phosphine–hydrazone bidentate ligands, such
as 2-diphenylphosphinobenzaldehyde SAMP hydrazone
(DPPBA–SAMP),3 and phosphine–amine bidentate lig-
ands, such as (S)-1-[2%-(diphenylphosphino)-1%-naph-
thalenyl]-2-(methoxymethyl)pyrrolidine, as efficient
chiral sources.4
Trost reported palladium-catalysed asymmetric allylic
alkylation using ligands 3, which, unlike 1, cannot serve
as bidentate diphosphine ligands.5 On the other hand,
Clayden has reported palladium-catalysed asymmetric
allylic alkylation using phosphine–amide ligand 4,
which has the chirality of a stereogenic axis and a
* 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)00037-4

288
T. Mino et al. / Tetrahedron: Asymmetry 12 (2001) 287–291
silicon-bearing stereogenic centre.8 Herein, we report
the palladium-catalysed asymmetric allylic alkylation
using new chiral phosphine–amide type ligands of the
type 5 and 6.
carried out in the presence of 2 mol% of [Pd(h3-
C3H5)Cl]2, 4 mol% of chiral ligand, and a mixture of
N,O-bis(trimethylsilyl)acetamide (BSA) and 2 mol% of
LiOAc at room temperature. We investigated the effect
of solvents on this reaction (Table 1). When the reac-
tion was carried out in ether, enantioselectivity was
higher than for the other solvents (Table 1, entry 1
versus entries 2–7). Using ligand 6, we obtained
product 11a in good yield (98%), but the enantiomeric
excess was a moderate 74% (entry 8).
2. Results and discussion
2.1. Synthesis of the phosphine–amide ligands
Ligand 5 was easily prepared from the reaction of
2-diphenylphosphinobenzoic acid with (S)-2-amino-1-
The use of NaOAc or KOAc instead of LiOAc,
decreased the enantioselectivity of 11a (entries 2 and 3,
Table 2). Using NaH as a base instead of BSA–LiOAc
also decreased both enantioselectivity and yield (entry
6). While reactivity depended slightly on reaction tem-
perature, the enantioselectivity was not temperature
dependent (entries 1 and 7–9). We obtained the highest
enantioselectivity at 4°C, with an e.e. of 85% (entry 7).
methoxy-3-phenylpropane9 in
(Scheme 1).
a
good 87% yield
Table 1. Asymmetric allylic alkylation using chiral phos-
phine–amide ligands 5 and 6a
Scheme 1.
Entry
Ligand
Solvent
Yield (%)b
E.e. (%)c
Ligand 6 was prepared by the amidation of methyl
2-hydroxy-1-naphthoate with (S)-2-amino-1-methoxy-
3-phenylpropane hydrochloride (AMPP·HCl) in the
presence of trimethylaluminium followed by the trifla-
tion of 7, and the nickel-catalysed phosphinylation of 8
(Scheme 2).
1
2
3
4
5
6
7
8
5
5
5
5
5
5
5
6
MeCN
DMF
THF
CH2Cl2
Ether
PhMe
Hexane
Ether
95
88
98
95
95
95
91
98
75
69
79
76
84
78
72
74
2.2. Palladium-catalysed asymmetric allylic alkylation
a The reaction was carried out at rt for 24 h.
b Isolated yields.
We then examined the chiral phosphine–amide ligands
5 and 6 in the palladium-catalysed asymmetric allylic
alkylation of 1,3-diphenyl-2-propenyl acetate 9a with
dimethyl malonate 10a (Scheme 3). This reaction was
c Determined by HPLC analysis using a chiral column (Chiralcel
OD).
Scheme 2.
Scheme 3.

T. Mino et al. / Tetrahedron: Asymmetry 12 (2001) 287–291
289
of the type 5 and using these ligands the palladium-
catalysed asymmetric allylic alkylation proceeded with
good enantiomeric excesses of up to 85%.
Table 2. Asymmetric allylic alkylation using chiral
phosphine–amide ligand 5a
Entry
Temp. (°C)
Base
Yield (%)b
E.e. (%)c
1
2
Rt
Rt
BSA–LiOAc 95
84
76
4. Experimental
BSA
94
–NaOAc
BSA–KOAc 95
BSA
4.1. General methods
3
4
Rt
Rt
78
74
98
Melting points were measured on a Yanagimoto or a
Shibata micromelting point apparatus. NMR spectra
were recorded on a JEOL A-400 or a Bruker DPX-300
system with TMS as an internal standard. IR spectra
were recorded on a Hitachi 260-10 or a JASCO FT/IR-
230 spectrometer. Mass spectra were recorded on a
JEOL JMS-HX110, a JEOL JMS-700, a Shimadzu
GCMS-QP2000A or a Hitachi M-80B mass spectrome-
ter. Optical rotations were measured on a JASCO
DIP-370 or an HORIBA SEPA-200 polarimeter.
–Cs2CO3
BSA–Li2CO3 91
NaH 34
BSA–LiOAc 94
BSA–LiOAc 93
BSA–LiOAc 98
5
6
7
Rt
Rt
74
42
85
83
84
4
8
−20
−35
9d
a The reaction was carried out for 24 h.
b Isolated yields.
c Determined by HPLC analysis using a chiral column (Chiralcel
OD).
d The reaction was carried out for 7 days.
4.2. Preparation of (S)-N-(1-benzyl-2-methoxyethyl)-2-
(diphenylphosphino)benzamide 5
When 1,3-diphenyl-2-propenyl pivalate 9b was used
instead of 1,3-diphenyl-2-propenyl acetate 9a, the reac-
tion with a dimethyl malonate 10a gave product 11a in
good yield with 84% e.e. (entry 2, Table 3). On the
other hand, with diethyl methylmalonate 10b, the reac-
tion gave the corresponding product 11b in low enan-
tioselectivity (entries 3 and 4).
To a mixture of DCC (3.0 mmol, 0.63 g), DMAP (0.13
mmol, 0.016 g) in CH2Cl2 (15 mL) was added (S)-(+)-2-
amino-1-methoxy-3-phenylpropane (2.5 mmol, 0.42 g)
and 2-(diphenylphosphino)benzoic acid (2.5 mmol, 0.77
g) at room temperature under an argon atmosphere.
After 24 h, the reaction mixture was filtered, evapo-
rated under reduced pressure, and purified by recrys-
tallisation from a CH2Cl2–hexane mixture: 87% (1.4
mmol, 0.63 g); mp 110–112°C. [h]2D0 −14.5 (c 0.80,
1
The H NMR of the 5·(p-allyl)Pd complex (lP 25.6)
showed a small downfield shift (Dl=0.45 ppm) of the
amidic proton relative to free 5, which indicates that
the Pd complex of ligand 5 was generated with a similar
P,O-chelation mode between phosphine and amide car-
bonyl, as observed in the case of ligand 2.7
1
CHCl3). H NMR (400 MHz, CDCl3): l 2.73–2.85 (m,
2H), 3.13–3.19 (m, 2H), 3.24 (s, 3H), 4.28–4.85 (m, 1H),
6.24 (d, J=8.3 Hz, 1H), 6.93–7.51 (m, 19H). 31P NMR
(CDCl3): l −9.92. 13C NMR (CDCl3): l 36.94, 50.65,
58.82, 71.54, 126.31–141.71 (m, Ar-C), 168.42. IR
(KBr): 3350, 3060, 2940, 2860, 2360, 1640, 1580, 1510,
1480, 1460, 1440, 1395, 1340, 1100, 740, 700 cm−1.
FABMS (m/z): 454 (M+1). HRMS (FAB) calcd for
C29H29NO2P (M+H): 454.1936; found: 454.1936.
3. Conclusion
We have prepared new chiral phosphine–amide ligands
Table 3. Asymmetric allylic alkylation using chiral phosphine–amide ligand 5a
Entry
9
10
11
Yield (%)b
E.e. (%)c
1
2
3
4
a
b
a
b
a
a
b
b
a
a
b
b
95
81
92
95
85
84
48
53
a The reaction was carried out for 24 h.
b Isolated yields.
c Determined by HPLC analysis using a chiral column (Chiralcel OD).

290
T. Mino et al. / Tetrahedron: Asymmetry 12 (2001) 287–291
4.5. Preparation of (S)-N-(1-benzyl-2-methoxyethyl)-2-
(diphenylphosphino)naphthalenecarboxamide 6
4.3. Preparation of (S)-N-(1-benzyl-2-methoxyethyl)-2-
hydroxynaphthalenecarboxamide 7
To a solution of NiCl2dppe (0.015 mmol, 0.008 g) in
DMF (0.3 mL) was added diphenylphosphine (0.4
mmol, 0.07 mL) at room temperature, and then the
resulting solution was heated at 100°C. After heating
at 100°C for 30 min, a solution of amide 8 (0.3 mmol,
0.140 g) and DABCO (0.34 mmol, 0.040 g) in DMF
(0.7 mL) was added at once, the resulting solution was
kept at 100°C for 24 h, and then the solution was
cooled to room temperature. The solution was diluted
with ethyl acetate and then washed with water and
brine. The organic phase was dried over Na2SO4, con-
centrated under reduced pressure and the residue was
purified by silica gel column chromatography to give 6
in 84% (0.25 mmol, 0.126 g) yield; mp 57.0–58.0°C.
[h]2D5 −18.7 (c 0.17, CHCl3). 1H NMR (300 MHz,
CDCl3): l 2.76–2.92 (m, 1H), 2.99–3.10 (m, 1H), 3.15
(s, 3H), 3.31–3.33 (m, 2H), 4.66–4.78 (m, 1H), 6.07 (d,
J=8.8 Hz, 1H), 7.10–7.17 (m, 1H), 7.19–7.38 (m,
15H), 7.38–7.44 (m, 1H), 7.45–7.54 (m, 1H), 7.55–7.67
(m, 1H), 7.68–7.74 (m, 1H), 7.75–7.82 (m, 1H). 31P
NMR (CDCl3): l −12.75. 13C NMR (CDCl3): l 37.32,
50.68, 58.77, 72.06, 125.75–142.85 (m, Ar-C), 168.40
(d, J=5.0 Hz). IR (KBr): 3409, 3293, 3054, 2923,
1656, 1496, 1251, 1182, 1120, 1026, 908, 817, 744, 698,
514 cm−1. FABMS (m/z): 504 (M+1). HRMS (FAB)
calcd for C33H31NO2P (M+H): 504.2092; found:
504.2072.
To a mixture of (S)-(+)-2-amino-1-methoxy-3-phenyl-
propane hydrochloride (2.0 mmol, 0.403 g) in benzene
(5 mL) was added a trimethylaluminium in hexane
(2.06 mmol, 2.1 mL, 0.98 M) at room temperature
under an argon atmosphere. The mixture was stirred
under reflux for 3 h and a benzene (3 mL) solution of
methyl 2-hydroxy-1-naphthoate (1.0 mmol, 0.202 g)
was added to the mixture. After 4 h, the reaction
mixture was cooled to room temperature. The mixture
was diluted with ethyl acetate and water. The organic
phase was washed with brine and dried over Na2SO4.
The filtrate was concentrated under reduced pressure
to give the residue, which was then purified by silica
gel column chromatography. Compound
7
was
afforded in 60% (0.60 mmol, 0.200 g) yield; mp 122.2–
123.0°C. [h]2D5 −54.4 (c 0.16, CHCl3). 1H NMR (300
MHz, CDCl3): l 3.00–3.12 (m, 2H), 3.40 (s, 3H), 3.48
(dd, J=3.5 and 9.5 Hz, 1H), 3.83 (dd, J=3.9 and 9.5
Hz, 1H), 4.62–4.67 (m, 1H), 6.64 (d, J=8.3 Hz, 1H),
7.15 (d, J=8.9 Hz, 1H), 7.23–7.40 (m, 6H), 7.41–7.46
(m, 1H), 7.75–7.81 (m, 2H), 7.87 (d, J=8.5 Hz, 1H),
11.31 (s, 1H). 13C NMR (CDCl3): l 37.40, 51.12,
59.10, 72.26, 109.82, 119.30, 122.54, 123.34, 126.77,
128.04, 128.69, 129.32, 129.37, 130.66, 133.78, 137.72,
159.29, 169.45. IR (KBr): 3261, 3178, 3068, 2950,
1637, 1540, 1513, 1436, 1344, 1292, 1263, 1207, 1105,
1072, 958, 829, 732, 698 cm−1. FABMS (m/z): 335
(M+1). HRMS (FAB) calcd for C21H22NO3 (M+H):
336.1600; found: 336.1583.
4.6. General procedure for asymmetric allylic
alkylations
To a mixture of [Pd(h3-C3H5)Cl]2 (0.01 mmol, 0.004
g), chiral amide (0.02 mmol), and lithium acetate (0.01
mmol, 0.001 g) in ether (1 mL) was added BSA (1.5
mmol, 0.37 mL), racemic 1,3-diphenyl-2-propenyl ace-
tate 9a (0.5 mmol, 0.126 g), and dimethyl malonate
10a (1.5 mmol, 0.17 mL) at room temperature under
an argon atmosphere. After stirring for 24 h, the reac-
tion 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 to give the residue, which was purified by
column chromatography to give 11a (Table 1, entry 5)
4.4. Preparation of (S)-N-(1-benzyl-2-methoxyethyl)-2-
(trifluoromethanesulfonyloxy)naphthalenecarboxamide 8
To a mixture of amide 7 (0.5 mmol, 0.167 g), pyridine
(1.2 mmol, 0.1 mL) and benzene (1 mL) was added
trifluoromethanesulfonic anhydride (0.83 mmol, 0.14
mL) at 0°C, and the mixture was stirred at room
temperature for 6 h. After removal of the solvent, the
residue was diluted with ethyl acetate and then washed
with 5% aq. HCl, satd NaHCO3, and brine. The
organic phase was dried over MgSO4 and concentrated
under reduced pressure. The residue was purified by
silica gel column chromatography to give 8 in 95%
(0.476 mmol, 0.222 g) yield; mp 127.0–127.7°C. [h]D25
1
in 95% yield; 84% e.e.; [h]2D0=+16.0 (c 1.0, EtOH); H
NMR (400 MHz, CDCl3): l 3.51 (s, 3H), 3.70 (s, 3H),
3.95 (d, J=11.0 Hz, 1H), 4.27 (dd, J=8.5 and 11.0
Hz, 1H), 6.44 (dd, J=8.5 and 15.8 Hz, 1H), 6.71 (d,
J=15.8 Hz, 1H), 7.19–7.33 (m, 10H); 13C NMR (100
MHz, CDCl3): l 49.20, 52.45, 52.63, 57.66, 126.40,
127.18, 127.58, 127.86, 128.48, 128.73, 129.12, 131.85,
136.83, 140.18, 167.79, 168.21; EIMS (m/z): 324 (M+,
30). 11b (Table 3, entry 4): 95% yield; 53% e.e.; [h]2D0=
1
−23.7 (c 0.35, CHCl3). H NMR (300 MHz, CDCl3): l
2.99–3.14 (m, 2H), 3.38 (s, 3H), 3.45–3.50 (m, 1H),
3.55 (dd, J=3.8 and 9.4 Hz, 1H), 4.68–4.78 (m, 1H),
6.43 (d, J=8.7 Hz, 1H), 7.25–7.40 (m, 6H), 7.47–7.55
(m, 3H), 7.84–7.88 (m, 1H), 7.93 (d, J=9.1 Hz, 1H).
13C NMR (CDCl3): l 37.55, 51.10, 58.94, 72.14,
118.58 (q, J=4.2 Hz), 118.86, 125.70, 126.62, 127.50,
128.06, 128.25, 128.44, 128.65, 129.53, 130.68, 131.63,
132.32, 137.89, 142.64, 163.36. IR (KBr): 3309, 3062,
2925, 1648, 1544, 1423, 1220, 1139, 954, 835, 813, 732,
617 cm−1. FABMS (m/z): 468 (M+1). HRMS (FAB)
calcd for C22H21F3NO5S (M+H): 468.1093; found:
468.1107.
1
+10.6 (c 1.0, EtOH); H NMR (400 MHz, CDCl3): l
1.13–1.28 (m, 6H), 1.47 (s, 3H), 4.04–4.18 (m, 2H),
4.14–4.20 (m, 2H), 4.29 (d, 8.9 Hz, 1H), 6.44 (d, 15.8
Hz, 1H), 6.71 (dd, 8.9 and 15.8 Hz, 1H), 7.18–7.34 (m,
10H); 13C NMR (100 MHz, CDCl3): l 13.94, 14.03,
18.81, 46.19, 53.72, 58.89, 61.34, 126.33, 127.10,
127.31, 128.20, 128.43, 128.86, 129.61, 132.58, 170.92,
171.19; EIMS (m/z): 366 (M+, 3).

T. Mino et al. / Tetrahedron: Asymmetry 12 (2001) 287–291
291
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