Design of a new class of chiral quinoline-phosphine ligands. Synthesis and application in asymmetric catalysis

Article abstract of DOI:10.1016/S0957-4166(01)00220-8

The design and synthesis of a new class of chiral quinoline-phosphine ligands has been achieved. Their efficiency as asymmetric ligands in enantioselective palladium-catalyzed allylic substitution reactions and in the asymmetric copper-catalyzed addition

Full text of DOI:10.1016/S0957-4166(01)00220-8

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 1345–1352
Design of a new class of chiral quinoline–phosphine ligands.
Synthesis and application in asymmetric catalysis
Guillaume Delapierre, Jean Michel Brunel, Thierry Constantieux and Ge´rard Buono*
Ecole Nationale Supe´rieure de Synthe`ses, de Proce´de´s et d’Inge´nierie Chimiques d’Aix Marseille, UMR CNRS 6516,
Faculte´ de St Je´roˆme, Av. Escadrille Normandie Niemen, 13397 Marseille Cedex 20, France
Received 24 April 2001; accepted 15 May 2001
Abstract—The design and synthesis of a new class of chiral quinoline–phosphine ligands has been achieved. Their efficiency as
asymmetric ligands in enantioselective palladium-catalyzed allylic substitution reactions and in the asymmetric copper-catalyzed
addition of diethylzinc to enones was also investigated. © 2001 Elsevier Science Ltd. All rights reserved.
zinc to enones.9 Herein, we report our investigations
into the synthesis of a new class of chiral quinoline–
1. Introduction
phosphine ligands analogous to QUIPHOS 1, varying
the nature of the chiral moiety and/or the substituents
attached to the quinoline group.
In recent years, various C2-symmetric and non-symmet-
ric chiral ligands bearing phosphine, nitrogen and/or
sulfur residues have been developed and used in numer-
ous transition-metal-catalyzed reactions1 such as
hydrogenation2 and allylic substitution.3 Thus, a wide
class of non-symmetric chiral PN- and SN-type com-
pounds were found to be efficient ligands for catalytic
asymmetric reactions on the basis of their electronic
and steric properties.4,5 In almost all cases, the phos-
phorus atom is not stereogenic but chiral oxazoline or
imidazoline moieties impart the chirality and have been
recognized as being important for inducing high enan-
tioselectivities.4b In the context of our studies, we have
recently described the synthesis of the new non-symmet-
ric homochiral P-quinoline phosphine ligand, (2R,5S)-
2-(8-quinolinoxy)-3-phenyl-1,3-diaza-2-phosphabicyclo-
[3.3.0]octane (QUIPHOS), with chirality at the phos-
phorus atom (Scheme 1).6
2. Results
The synthesis of this new class of bidentate chiral
ligands was easily achieved by an exchange reaction
between tris(dimethylamino)phosphine and a chiral
auxiliary such as a diamine, a diol or an aminoalcohol
in refluxing toluene followed by addition of 1 equiv. of
the desired substituted hydroxyquinoline (Scheme 2).
Thus, we first modified the structure of the chiral
moiety attached to the phosphorus atom of the original
QUIPHOS compound. In this case, the desired ligands
2–7 were easily obtained in workable yields varying
from 48 to 62% (Scheme 3).
Due to its high stability, this ligand has been success-
fully used in asymmetric palladium-catalyzed allylic
substitutions,7 copper-catalyzed Diels–Alder reactions8
and the enantioselective conjugate addition of diethyl-
Modification of the quinoline structure was also
envisaged10 and was completed as outlined above. Lig-
ands 8–14, analogous to the QUIPHOS structure, were
synthesized in moderate to good yields and character-
ized by NMR spectroscopy (Table 1).
The catalytic properties of the palladium complexes
formed in situ from these ligands and [Pd(allyl)Cl]2 in
an allylic substitution of 1,3-diphenyl-2-propenyl ace-
tate 15 by benzylamine or a nucleophile generated from
dimethylmalonate with bis(trimethylsilyl)acetamide
(BSA) and a small amount of potassium acetate were
investigated under the best reported7 experimental con-
ditions (Table 2).
Scheme 1.
* Corresponding author.
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00220-8

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G. Delapierre et al. / Tetrahedron: Asymmetry 12 (2001) 1345–1352
Scheme 2.
Scheme 3.
Table 1. Synthesis of various substituted QUIPHOS ligands
a
Isolated yield.
b
Diastereomeric ratio determined by 31P NMR spectroscopy analysis (see Ref. 11).

G. Delapierre et al. / Tetrahedron: Asymmetry 12 (2001) 1345–1352
1347
Replacement of the (S)-2-anilinomethyl pyrrolidine
moiety in ligands 2–7 led to a significant decrease in
catalytic efficiency. Poor conversions and low e.e.s were
observed, demonstrating the importance of this struc-
ture on the outcome of the reaction. On the other hand,
slight modifications at the quinoline group led in almost
Table 2. Enantioselective catalytic palladium allylic substitution using various substituted QUIPHOS ligands
Entrya
Ligand
16
17
Yield (%)
E.e. (%)
Yield (%)
E.e. (%)
1
2
3
4
5
6
7
1
2
3
4
5
100
78
81
86
91
93 (S)
12 (S)
6 (S)
35 (S)
33 (S)
0
100
94
68
79
89
85 (R)
15 (R)
10 (R)
27 (R)
31 (R)
29 (R)
–
6
7
0
2
56
0
n.d.
8
9
8
9
60
38 (S)
72 (S)
59 (S)
60 (S)
76 (S)
78 (S)
50 (S)
100
100
100
95
75
75
42 (R)
64 (R)
41 (R)
74 (R)
41 (R)
36 (R)
48 (R)
100
100
15
100
83
10
11
12
13
14
10
11
12
13
14b
100
93
a Conversion and e.e. determined by HPLC analysis on a Daicel Chiralcel OD-H column using hexane/i-PrOH (200:1) as eluent (254 nm, 1
mL/min; see Section 4).
b Mixture of diastereomeric ligands (77:23).
Table 3. Enantioselective Cu(I)-catalyzed additions of Et2Zn to cyclohexenone using ligands 1–14
Entrya
Ligand
No additive
E.e. (%)
Zn(OH)2 (0.25 equiv.)
E.e. (%)
Yield (%)
Yield (%)
1
2
3
4
1
2
3
100
84
100
64
7
25
0
100
91
68
53
20
2
4
0
67
1
5
5
0
–
0
–
6
7
8
9
10
11
12
13
14
6
7
8
9
10
11
12
13
14b
84
27
2
89
98
100
100
97
25
2
100
100
100
97
35
30
25
38
40
41
46
42
29
15
44
50
51
55
95
95
100
100
96
100
100
96
a Conversion and e.e. determined by GC analysis on a Macherey Nagel FS-Lipodex E column, 25 m×0.25 mm, He pressure 60 kPa, 58–115°C,
3°C/min (see Section 4).
b Mixture of diastereomeric ligands (77:23).

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G. Delapierre et al. / Tetrahedron: Asymmetry 12 (2001) 1345–1352
all cases to good conversions varying from 75 to 100%
(entries 8–14). Depending on the nature of the sub-
stituent attached to the quinoline ring, poor to moder-
ate enantioselectivities were seen and enantio-
selectivities were less good than those seen using
QUIPHOS 1. At this time it is difficult to correlate the
influence of the structural features and the observed
e.e.s.
4.1. Synthesis of 2-substituted-8-hydroxyquinoline
4.1.1. 2-Phenyl-8-hydroxyquinoline. 2-Phenyl-8-hydroxy-
quinoline was synthesized following a modification of
the procedure reported by Merritt et al.13 To a stirred
suspension of lithium metal (0.841 g, 0.121 mol) in
diethyl ether (50 mL) under argon was added dropwise
bromobenzene (9.09 g, 57.9 mmol). After stirring the
mixture for 40 min, a solution of 8-hydroxyquinoline
(4.00 g, 27.6 mmol) in diethyl ether (80 mL) was slowly
added. The solution was then stirred under reflux for 1
h, cooled to rt and air was bubbled through the mixture
for 2 h. Water (40 mL) and diethyl ether (80 mL) were
slowly added and the solution was neutralized (HCl
33%). The two phases were separated and the aqueous
layer was extracted with dichloromethane (4×40 mL).
The combined organic layers were dried (Na2SO4),
filtered and evaporated. The residue was distilled at
reduced pressure (0.03 mbar, 160–165°C) to afford
2-phenyl-8-hydroxyquinoline (4.34 g, 56%) as a pale
yellow solid; mp 55°C; IR (KBr): w 3396 (OꢀH str.),
3076–3046 (CꢀH str. Ar); 1H NMR: l 8.25–8.50 (s
large, 1H), 8.12–8.19 (m, 3H), 7.85 (d, 1H, J=8.6 Hz),
7.49–7.60 (m, 3H), 7.43 (d, 1H, J=7.4 Hz), 7.32 (dd,
1H, J=1.3, 8.2 Hz), 7.26 (dd, 1H, J=1.4, 7.4 Hz); 13C
NMR: l 154.7, 152.1, 138.5, 137.8, 136.8, 129.4, 128.7,
127.3, 127.2, 119.3, 117.5, 110.0.
On the basis of our recent results,9 we tested these
ligands in the asymmetric copper-catalyzed addition of
diethylzinc to cyclohexenone as test substrate12 (Table
3).
Irrespective of the experimental conditions applied,
good conversions (>90%) were seen in all cases. A
significant improvement in the product e.e. from 7 to
53% was observed when the reaction was completed in
the presence of Zn(OH)2 (Table 2, entry 1). The benefi-
cial effect on the selectivity of the reaction using the
Zn(OH)2 additive can be rationalized on the basis of its
Lewis acid properties. Thus, it can be postulated that
complexation of Zn to the enone carbonyl group
increases the enantiofacial differentiation and enhances
the enantioselectivity of the reaction. As discussed
above, ligands 2–7 led to poor results in terms of
enantioselectivity, varying from 2 to 12% e.e. (Table 2,
entries 2–7). Ligands 8–14 led to lower or similar e.e.s
and yields to those previously obtained using
QUIPHOS 1, underlining the importance of the ligand
structure on the enantioselectivity of the reaction.
4.1.2. 2-tert-Butyl-8-hydroxyquinoline. 2-tert-Butyl-8-
hydroxyquinoline was synthesized from tert-BuLi (24.3
mL, 1.7 M in pentane, 41.3 mmol) and 8-hydroxy-
quinoline (2.00 g, 13.7 mmol) according to the same
procedure previously described. The residue was
purified by silica gel chromatography (petroleum ether/
ethyl acetate, 20:1) to afford 2-tert-butyl-8-hydroxy-
quinoline as a clear liquid (1.16 g, 42% yield); IR (neat):
w 3395 (OꢀH str.), 3056–3000 (CꢀH str. Ar), 2964–2872
3. Conclusion
The design and synthesis of a new class of chiral
quinoline–phosphine ligands has been achieved and
their efficiency in both enantioselective palladium-cata-
lyzed allylic substitution reactions and enantioselective
copper-catalyzed diethylzinc addition to enones has
been investigated. Further studies are now in progress
in order to extend the use of these ligands to other
catalytic asymmetric reactions.
1
(CꢀH str. Al); H NMR: l 8.20–8.55 (s large, 1H), 8.06
(d, 1H, J=8.7 Hz), 7.50 (d, 1H, J=8.7 Hz), 7.37 (t, 1H,
J=7.8 Hz), 7.25 (dd, 1H, J=1.4, 8.2 Hz), 7.14 (dd, 1H,
J=1.4, 7.3 Hz), 1.45 (s, 9H); 13C NMR: l 167.2, 151.9,
136.8, 136.2, 126.7, 126.5, 119.0, 117.3, 109.4, 37.9,
30.0.
4.1.3. 2-Cyano-8-hydroxyquinoline. 2-Cyano-8-hydroxy-
quinoline was prepared from 8-hydroxyquinoline in
37% yield according to the reported procedure.14 Spec-
tral data were in agreement with those reported in the
literature.15
4. Experimental
Tetrahydrofuran (THF) and toluene were distilled from
sodium/benzophenone ketyl immediately prior to use.
Ethyl acetate and petroleum ether (35–60°C) were pur-
chased from SDS and used without any further purifi-
cation. Column chromatography was performed on
4.1.4. 2-(4%,4%-Dimethyl-2%-oxazoline)-8-hydroxyquinoline.
A mixture of 2-cyano-8-hydroxyquinoline (500 mg, 2.94
mmol), 2-amino-2-methylpropanol (593 mg, 6.65
1
SDS silica gel (70–230 mesh). H and 13C NMR spectra
mmol) and powdered 4 A molecular sieves (1.00 g) in
,
were recorded in CDCl3 solution at 200.00 and 50.30
MHz on a Bruker AC200 instrument; 31P NMR spectra
were recorded in CDCl3 solution at 40.50 MHz on a
Bruker AC100 (the usual abbreviations are used: s,
singlet; d, doublet; t, triplet; q, quadruplet; m, multi-
plet). The positive chemical shift values are given in
ppm, while the coupling constants are in hertz. Specific
rotations were determined with a Perkin–Elmer 341
polarimeter.
1,2-dichlorobenzene (5 mL) was stirred under reflux for
60 h under argon. The mixture was cooled to rt, diluted
with dichloromethane (30 mL), filtered and evaporated.
The evaporation residue was purified by silica gel chro-
matography (petroleum ether/THF, 2:1) to afford 2-
(4%,4%-dimethyl-2%-oxazoline)-8-hydroxyquinoline as
a
yellow solid (485 mg, 68% yield); mp 97°C; IR (KBr): w
3376 (OꢀH str.), 3087–3046 (CꢀH str. Ar), 2987–2877
1
(CꢀH str. Al); H NMR: l 8.22–8.60 (s large, 1H), 7.91

G. Delapierre et al. / Tetrahedron: Asymmetry 12 (2001) 1345–1352
1349
(d, 2H, J=3.8 Hz), 7.26 (d, 1H, J=7.9 Hz), 7.07 (d,
2H, J=7.9 Hz), 4.04 (s, 2H), 1.26 (s, 6H); 13C NMR: l
161.0, 152.9, 143.8, 137.4, 136.0, 128.8, 128.6, 120.6,
117.1, 110.8, 79.2, 67.4, 27.9.
major eluting band was evaporated to afford 3 as a
colorless oil in 48% yield (ratio anti:syn=73:26); [h]D=
+42.1 (c 1.30, CH2Cl2); IR (neat): w 3062–3038 (CꢀH
str. Ar), 2977–2898 (CꢀH str. Al); 31P NMR: l 138.1
(anti), 144.1 (syn); 1H NMR: l (anti) 8.80 (dd, 1H,
J=4.2, 16.4 Hz), 8.12 (d, 1H, J=8.3 Hz), 7.14–7.54 (m,
10H), 4.70 (dd, 1H, J=2.4, 9.5 Hz), 2.90 (d, 3H,
J=13.5 Hz), 1.21 (d, 3H, J=5.7 Hz); 13C NMR: l
(anti) 152.2, 149.1, 149.0, 139.6, 135.7, 129.8, 128.4,
128.1, 127.6, 126.7, 121.9, 121.3, 118.6 (d, J=7.1 Hz),
91.5 (d, J=10.5 Hz), 61.2 (d, J=5.9 Hz), 29.5 (d,
J=12.9 Hz), 14.9 (d, J=6.3 Hz).
4.1.5. (E)-2-(2-Phenylethenyl)-8-hydroxyquinoline. (E)-
2-(2-Phenylethenyl)-8-hydroxyquinoline was synthe-
sized following a procedure reported by Merritt et al.13
Spectral data were in agreement with those reported in
the literature.15
4.1.6. (E)-2-(2-Phenylethyl)-8-hydroxyquinoline. A mix-
ture of (E)-2-(2-phenylethenyl)-8-hydroxyquinoline
(1.00 g, 4.04 mmol) and 5% Pd/C (861 mg, 0.404 mmol)
in ethyl acetate was stirred at rt under hydrogen at
atmospheric pressure for 12 h. The mixture was then
filtered through Celite and evaporated. The residue was
purified by silica gel chromatography (petroleum ether/
ethyl acetate, 10:1) to afford (E)-2-(2-phenylethyl)-8-
hydroxyquinoline (515 mg, 51% yield) as a pale yellow
oil; IR (neat): w 3397 (OꢀH str.), 3070–3002 (CꢀH str.
4.2.3. (3S,4R)-2,3-Dimethyl-4-phenyl-1-(8-quinolinoxy)-
2-aza-5-oxa-1-phosphacylopentane 4. Purified by silica
gel chromatography (THF/petroleum ether, 1:5) in 50%
yield (100% anti diastereomer) as a colorless oil; [h]D=
+30.5 (c 0.38, CH2Cl2); IR (neat): w 3062–3033 (CꢀH
str. Ar), 2971–2813 (CꢀH str. Al); 31P NMR: l 137.5;
1H NMR: l 8.93 (d, 1H, J=4.4 Hz), 8.12 (d, 1H,
J=7.8 Hz), 7.34–7.48 (m, 10H), 5.96 (d, 1H, J=7.2
Hz), 2.98 (d, 3H, J=12.2 Hz), 0.71 (d, 3H, J=6.5 Hz);
13C NMR: l 150.6, 149.1, 147.8, 138.0, 135.7, 129.6,
128.0 (×2), 127.6, 126.7 (d, J=8.1 Hz), 122.0, 121.3,
118.8 (d, J=7.2 Hz), 84.7 (d, J=8.7 Hz), 57.6 (d,
J=5.8 Hz), 29.5 (d, J=17.3 Hz), 14.7 (d, J=3.7 Hz).
1
Ar), 2971–2861 (CꢀH str. Al); H NMR: l 8.15–8.50 (s
large, 1H), 8.04 (d, 1H, J=8.4 Hz), 7.22–7.49 (m, 9H),
3.18–3.39 (m, 4H); 13C NMR: l 159.4, 151.8, 141.3,
137.6, 136.2, 128.4 (×2), 126.8, 126.7, 126.0, 122.3,
117.6, 109.8, 39.9, 35.2.
4.2.4. (R)-4-(8-Quinolinoxy)-3,5-dioxa-4-phosphacyclo-
hepta-[2,1-a;3,4-a%]binaphthalene 5. Purified by silica gel
chromatography (THF/petroleum ether, 1:6) in 56%
yield as a colorless oil; [h]D=−155 (c 0.23, THF); IR
(neat): w 3060–3021 (CꢀH str. Ar), 2967–2891 (CꢀH str.
Al); 31P NMR (C6D6): l 141.3; 1H NMR (C6D6): l
8.76–8.80 (dd, 1H, J=1.5, 4.2 Hz), 7.47–7.69 (m, 7H),
7.15–7.40 (m, 6H), 6.93–7.10 (m, 3H), 6.71–6.80 (m,
1H); 13C NMR (C6D6): l 153.6, 150.6, 150.3, 149.3,
149.0, 148.6, 135.9, 134.4, 133.4 (d, J=14.1 Hz), 131.8
(d, J=18.6 Hz), 130.6, 129.9, 129.8, 128.7 (d, J=2.7
Hz), 127.4, 127.0, 126.6, 126.4, 125.1, 125.0, 123.8,
123.0, 122.7, 122.5, 121.8, 118.8 (d, J=2.1 Hz), 118.4.
4.2. General procedure for the synthesis of ligands
Diamine or aminoalcohol (3 mmol) was placed in a 25
mL two-necked round-bottomed flask under argon.
Dry toluene (3 mL) and tris(dimethylamino)phosphine
(3 mmol) were added. The solution was heated under
reflux for 2 h and cooled to rt. A solution of 8-hydroxy-
quinoline or 2-substituted-8-hydroxyquinoline (3 mmol)
in dry toluene (1 mL) was added under argon. The
solution was then heated under reflux for 2 h and then
cooled to rt. Purification was achieved by precipitation
at the end of the reaction or by silica gel chromatogra-
phy as described for each compound.
4.2.5. (1R,5R)-2,4-Dimethyl-3-(8-quinolinoxy)-2,4-diaza-
3-phosphabicyclo[4.3.0]nonane 6. Purified by silica gel
chromatography (THF/petroleum ether, 1:2) in 61%
yield as a colorless oil; [h]D=−9.83 (c 0.60, CH2Cl2); IR
(neat): w 3052–3010 (CꢀH str. Ar), 2936–2801 (CꢀH str.
Al); 31P NMR: l 147.5; 1H NMR: l 8.64 (dd, 1H,
J=1.5, 4.2 Hz), 7.97 (dd, 1H, J=1.5, 8.3 Hz), 7.05–
7.34 (m, 4H), 2.98 (d, 3H, J=12.8 Hz), 2.66 (d, 3H,
J=15.1 Hz), 2.07–1.94 (m, 2H), 1.65–1.73 (m, 2H),
0.95–1.28 (m, 4H); 13C NMR: l 152.5 (d, J=2.3 Hz),
148.5, 141.9 (d, J=1.7 Hz), 135.6, 129.6, 126.6, 121.1,
121.0, 119.1 (d, J=4.0 Hz), 69.6 (d, J=8.0 Hz), 65.2 (d,
J=7.5 Hz), 33.4 (d, J=32.7 Hz), 30.4 (d, J=10.9 Hz),
29.4, 28.7 (d, J=3.4 Hz), 24.1 (×2).
4.2.1. (3R,4R)-3,4-Diphenyl-2,5-dimethyl-1-(8-quinolin-
oxy)-2,5-diaza-1-phosphacyclopentane 2. Purified by pre-
cipitation at the end of the reaction by the addition of
hexane (0.2 mL). The mixture was filtered and the filter
cake dried to afford 2 as a pale yellow solid (51% yield);
mp 86°C; [h]D=+17.2 (c 1.02, CH2Cl2); IR (neat): w
3084–3006 (CꢀH str. Ar), 2987–2807 (CꢀH str. Al); 31P
1
NMR (C6D6): l 139.9; H NMR (C6D6): l 8.77 (dd,
1H, J=1.5, 3.9 Hz), 7.74 (dd, 1H, J=1.5, 8.1 Hz),
7.55–7.63 (m, 3H), 7.16–7.45 (m, 10H), 6.92–7.01 (m,
1H), 4.82 (dd, 1H, J=3.9, 9.0 Hz), 4.48 (dd, 1H,
J=3.3, 9.3 Hz), 3.14 (d, 3H, J=10.8 Hz), 3.85 (d, 3H,
J=14.7 Hz); 13C NMR (C6D6): l 153.8 (d, J=2.0 Hz),
148.6, 142.8, 140.8, 140.2 (d, J=5.2 Hz), 135.6, 130.3,
128.7, 128.6 (×2), 128.5, 127.9, 127.6, 127.2, 121.3,
121.2, 119.1 (d, J=3.6 Hz), 79.3 (d, J=10.3 Hz), 77.7
(d, J=8.8 Hz), 33.8 (d, J=28.6 Hz), 32.6 (d, J=12.9
Hz).
4.2.6.
(2R,5S)-2-(8-Quinolinoxy)-1-aza-3-oxa-2-phos-
phabicyclo[3.3.0]octane 7. A solution of HCl (2 M in
Et2O, 7 mL, 14 mmol) and Et2O (13 mL) was cooled to
0°C in a 50 mL two-necked round-bottomed flask
under argon. A solution of (S)-prolinol (10 mmol) in
Et2O (2 mL) was slowly added. The mixture was stirred
for 1 h at rt, then evaporated, washed with petroleum
ether (3×7 mL) and dried under vacuum. Dry toluene
4.2.2. (3S,4S)-2,3-Dimethyl-4-phenyl-1-(8-quinolinoxy)-
2-aza-5-oxa-1-phosphacylopentane 3. Purified by silica
gel chromatography (THF/petroleum ether, 1:5). The

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G. Delapierre et al. / Tetrahedron: Asymmetry 12 (2001) 1345–1352
(12 mL) and tris(dimethylamino)phosphine (10 mmol)
were added. The solution was stirred under reflux for 2
h and then cooled to rt. 8-Hydroxyquinoline (10 mmol)
was added under argon. The solution was then stirred
under reflux for 2 h and cooled to rt. After evaporation
of the solvent, the residue was distilled under reduced
pressure (5×10−3 mbar, 155–170°C) to afford com-
pound 7 as a pale yellow oil (616 mg, 23%); [h]D=
+10.7 (c 1.1, CH2Cl2); IR (neat): w 3074–3025 (CꢀH str.
Ar), 2964–2873 (CꢀH str. Al); 31P NMR: l 152.2 (anti),
137.3 (syn); 1H NMR: l 8.00 (d, 1H, J=8.3 Hz),
7.09–7.45 (m, 5H), 3.75–4.07 (m, 3H), 2.95–3.19 (m,
2H), 1.41–2.02 (m, 4H); 13C NMR: l (anti)=152.0,
148.4, 140.7, 135.5, 129.3, 126.5, 121.2, 120.9, 117.6 (d,
J=5.7 Hz), 72.7 (d, J=9.0 Hz), 61.6 (d, J=4.4 Hz),
46.5 (d, J=33.2 Hz), 31.0, 26.1 (d, J=2.5 Hz).
168.1, 150.6, 145.5 (d, J=14.9 Hz), 141.4, 135.7, 129.0,
127.7, 125.5, 122.0, 120.4 (d, J=4.6 Hz), 119.1, 118.2,
115.5 (d, J=12.3 Hz), 62.7 (d, J=8.7 Hz), 53.7 (d,
J=7.0 Hz), 48.0 (d, J=33.6 Hz), 38.3, 31.5, 30.2, 26.3
(d, J=4.3 Hz).
4.2.10. (2R,5S)-3-Phenyl-2-(2-cyano-8-quinolinoxy)-1,3-
diaza-2-phosphabicyclo[3.3.0]octane 11. Purified by silica
gel chromatography (THF/petroleum ether, 1:5) to
afford 11 as a colorless oil in 72% yield (100% anti
diastereomer); [h]D=−397 (c 1.01, CH2Cl2); IR (neat): w
3067–3046 (CꢀH str. Ar), 2967–2877 (CꢀH str. Al),
1
2239 (CN str.); 31P NMR: l 134.3; H NMR: l 8.25 (d,
1H, J=8.4 Hz), 7.65 (d, 1H, J=8.4 Hz), 7.56 (d, 1H,
J=2.7 Hz), 7.54 (s, 1H), 7.23–7.32 (m, 3H), 7.08–7.14
(m, 2H), 6.88 (t, 1H, J=7.2 Hz), 4.01–4.15 (m, 1H),
3.79–3.99 (m, 2H), 3.55–3.69 (m, 1H), 3.28–3.39 (m,
1H), 1.85–2.11 (m, 3H), 1.56–1.69 (m, 1H); 13C NMR:
l 152.1, 145.1 (d, J=15.0 Hz), 142.3, 137.4, 132.0,
130.1, 129.9, 129.0, 123.4, 121.6, 121.4 (d, J=3.4 Hz),
119.3, 117.6, 115.4 (d, J=14.1 Hz), 62.7 (d, J=8.8 Hz),
53.4 (d, J=7.9 Hz), 48.0 (d, J=32.4 Hz), 31.7, 26.5 (d,
J=4.2 Hz).
4.2.7. (2R,5S)-3-Phenyl-2-(2-methyl-8-quinolinoxy)-1,3-
diaza-2-phosphabicyclo[3.3.0]octane 8. Purified by silica
gel chromatography (THF/petroleum ether, 1:5) in 49%
yield as a colorless oil (100% anti diastereomer); [h]D=
−388 (c 1.15, CH2Cl2); IR (neat): w 3056–3010 (CꢀH str.
1
Ar), 2964–2872 (CꢀH str. Al); 31P NMR: l 129.5; H
NMR: l 8.00 (d, 1H, J=8.4 Hz), 7.45 (d, 1H, J=7.6
Hz), 7.1–7.35 (m, 7H), 6.86 (t, 1H, J=6.9 Hz), 4.00 (q,
1H, J=6.4 Hz), 3.71–3.83 (m, 2H), 3.40–3.50 (m, 1H),
3.22–3.32 (m, 1H), 2.76 (s, 3H), 1.55–2.02 (m, 4H); 13C
NMR: l 157.8, 150.9, 145.6 (d, J=14.6 Hz), 141.83,
135.9, 129.0, 128.9, 127.9, 125.7, 122.0 (d, J=5.2 Hz),
120.2 (d, J=3.9 Hz), 119.0, 115.5 (d, J=13.4 Hz), 62.7
(d, J=8.9 Hz), 53.6 (d, J=7.5 Hz), 48.3 (d, J=33.4
Hz), 31.7, 26.5 (d, J=4.2 Hz), 25.4.
4.2.11. (2R,5S)-3-Phenyl-2-((E)-2-(2-phenylethenyl)-8-
quinolinoxy)-1,3-diaza-2-phosphabicyclo[3.3.0]octane 12.
Purified by silica gel chromatography (THF/petroleum
ether, 1:10) to afford 12 as a pale yellow solid in 22%
yield (ratio anti:syn=92:8); mp 52–65°C; [h]D=−372 (c
0.97, CH2Cl2); IR (KBr): w 3067–3047 (CꢀH str. Ar),
2967–2877 (CꢀH str. Al); 31P NMR: l 127.4 (anti),
1
122.4 (syn); H NMR: l (anti)=8.07 (d, 1H, J=8.6
Hz), 7.16–7.76 (m, 15H), 6.85–6.96 (m, 1H), 3.60–3.95
(m, 3H), 3.20–3.45 (m, 2H), 1.55–2.05 (m, 4H); 13C
NMR: l (anti)=154.9, 151.1, 145.6 (d, J=15.9 Hz),
142.3, 136.6, 136.0, 133.8, 129.5, 129.0, 128.7 (×2),
128.5, 128.3, 127.1, 126.2, 122.0, 120.5 (d, J=5.3 Hz),
119.0 (d, J=6.0 Hz), 115.5 (d, J=13.1 Hz), 62.7 (d,
J=9.0 Hz), 53.7 (d, J=7.3 Hz), 47.9 (d, J=33.5 Hz),
31.6, 26.5 (d, J=4.2 Hz).
4.2.8. (2R,5S)-3-Phenyl-2-(2-phenyl-8-quinolinoxy)-1,3-
diaza-2-phosphabicyclo[3.3.0]octane 9. Purified by pre-
cipitation at the end of the reaction. The mixture was
filtered and the filter cake dried to afford 9 as a white
solid (100% anti diastereomer) in 45% yield; mp 145°C;
[h]D=−466 (c 1.05, CH2Cl2); IR (KBr): w 3067–3000
(CꢀH str. Ar), 2977–2847 (CꢀH str. Al); 31P NMR: l
129.0; 1H NMR: l 8.30 (d, 1H, J=7.9 Hz), 8.28 (d, 1H,
J=7.0 Hz), 8.18 (d, 1H, J=8.6 Hz), 7.89 (d, 1H, J=8.6
Hz), 7.45–7.60 (m, 4H), 7.30–7.45 (m, 1H), 7.20–7.30
(m, 5 H), 6.89–6.96 (q, 1H, J=4.1 Hz), 3.75–4.00 (m,
2H), 3.50–3.65 (m, 1H), 3.05–3.35 (m, 2H), 1.50–2.00
(m, 4H); 13C NMR: l 155.9, 151.4, 145.5 (d, J=16.0
Hz), 142.1, 139.5, 136.8, 129.3 (×2), 128.7, 127.9, 126.5,
122.1, 120.6 (d, J=4.6 Hz), 119.3, 118.8, 115.8 (d,
J=13.0 Hz), 62.9 (d, J=8.8 Hz), 53.9 (d, J=7.3 Hz),
48.0 (d, J=32.8 Hz), 31.7, 26.6 (d, J=4.0 Hz).
4.2.12.
(2R,5S)-3-Phenyl-2-((E)-2-(2-phenylethyl)-8-
quinolinoxy)-1,3-diaza-2-phosphabicyclo[3.3.0]octane 13.
Purified by silica gel chromatography (THF/petroleum
ether, 1:8) to afford 10 as a pale yellow solid in 51%
yield (ratio anti:syn=97:3); mp 112°C; [h]D=−341 (c
1.07, CH2Cl2); IR (KBr): w 3067–3047 (CꢀH str. Ar),
2967–2847 (CꢀH str. Al); 31P NMR: l 129.1 (anti),
1
122.6 (syn); H NMR: l (anti) 8.03 (d, 1H, J=8.4 Hz),
7.48 (d, 1H, J=8.0 Hz), 7.21–7.40 (m, 12H), 6.80–7.00
(m, 1H), 4.04 (q, 1H, J=6.5 Hz), 3.65–3.90 (m, 2H),
3.15–3.52 (m, 6H), 1.80–2.10 (m, 3H), 1.55–1.72 (m,
1H); 13C NMR: l (anti)=160.6, 150.9, 145.5 (d, J=
15.9 Hz), 141.9, 141.6, 135.9, 128.9, 128.4, 128.3 (×2),
128.1, 125.8 (d, J=4.1 Hz), 122.0, 121.4, 120.2 (d,
J=4.6 Hz), 119.0, 115.5 (d, J=13.2 Hz), 62.7 (d, J=8.8
Hz), 53.6 (d, J=7.3 Hz), 48.0 (d, J=33.4 Hz), 40.9,
35.8, 31.6, 26.4 (d, J=4.1 Hz).
4.2.9. (2R,5S)-3-Phenyl-2-(2-tert-butyl-8-quinolinoxy)-
1,3-diaza-2-phosphabicyclo[3.3.0]octane 10. Purified by
silica gel chromatography (ethyl acetate/petroleum
ether, 1:20) to afford 10 as a white solid in 35% yield
(100% anti diastereomer); mp 110°C; [h]D=−395 (c
1.00, CH2Cl2); IR (KBr): w 3073–3054 (CꢀH str. Ar),
1
2978–2872 (CꢀH str. Al); 31P NMR: l 128.8; H NMR:
l 9.48 (d, 1H, J=8.7 Hz), 8.95 (d, 1H, J=8.7 Hz), 8.89
(dd, 1H, J=1, 8.0 Hz), 8.68–8.75 (m, 2H), 8.62–8.67
(m, 3H), 8.55 (dd, 1H, J=1.0, 7.3 Hz), 8.27–8.35 (m,
1H), 5.16–5.35 (m, 2H), 4.97–5.13 (m, 1H), 4.50–4.72
(m, 2H), 3.04–3.40 (m, 4H), 2.95 (s, 9H); 13C NMR: l
4.2.13. (2R,5S)-3-Phenyl-2-(2-(4%,4%-dimethyl-2%-oxazo-
line)-8-quinolinoxy)-1,3-diaza-2-phosphabicyclo[3.3.0]oc-
tane oxazoline 14. Purified by silica gel chromatography
(THF/petroleum ether, 1:2) to afford 14 as a pale yellow

G. Delapierre et al. / Tetrahedron: Asymmetry 12 (2001) 1345–1352
1351
solid in 46% yield (ratio anti:syn=77:23); mp 50–55°C;
[h]D=−277 (c 0.86, CH2Cl2); IR (KBr): w 3067–3046
(CꢀH str. Ar), 2977–2877 (CꢀH str. Al); 31P NMR: l
128.9 (anti), 123.6 (syn); 1H NMR: l (anti) 8.14 (s,
2H), 6.75–7.50 (m, 8H), 4.22 (s, 2H), 3.55–3.90 (m, 2H),
3.10–3.40 (m, 1H), 1.40–2.05 (m, 6H), 1.42 (s, 6H); 13C
NMR: l (anti) 162.0, 151.8, 146.0, 145.3 (d, J=15.4
Hz), 141.6, 136.1, 129.8, 129.1, 128.8, 127.9, 121.8,
120.9, 118.9, 115.4, (d, J=13.2 Hz), 79.3, 67.7, 62.6 (d,
J=8.9 Hz), 53.5 (d, J=7.5 Hz), 47.6 (d, J=33.4 Hz),
31.5, 28.4, 28.2, 26.3 (d, J=4.4 Hz).
and the mixture was extracted with Et2O (3×10 mL).
The combined organic layers were dried over MgSO4,
concentrated in vacuo and filtered on silica gel
(dichloromethane, 20 mL). Conversion and e.e.s were
determined by gas chromatography on a Macherey
Nagel FS-Lipodex E column, 25 m×0.25 mm, He pres-
sure 60 kPa, 58–115°C, 3°C/min; tR=14.8 (2-cyclo-
hexenone), 16.2 (R), 16.6 min (S).
Acknowledgements
4.3. General procedure for asymmetric allylic alkyl-
ation of 1,3-diphenyl-2-propenyl acetate
The authors would like to thank the CNRS for finan-
cial support. G.D. acknowledges MENRT for the
award of a doctoral fellowship.
A mixture of [Pd(allyl)Cl]2 (3 mg, 8.2×10−3 mmol, 2
mol%) and the desired ligand (33×10−3 mmol) in anhy-
drous CH2Cl2 was stirred at rt for 15 min. A solution of
1,3-diphenylprop-3-en-1-yl acetate (100 mg, 0.396
mmol) was added and stirring was maintained for 5
min. Dimethylmalonate (157 mg, 1.18 mmol), N,O-
bis(trimethylsilyl)acetamide (BSA, 241 mg, 1.18 mmol)
and a catalytic amount of potassium acetate (KOAc)
were subsequently added. The resulting solution was
stirred at 25°C for 12 h. The solution was diluted with
Et2O (3×10 mL). The combined organic phases were
dried over MgSO4 and filtered. The solvent was
removed in vacuo to afford a pale yellow oil that
solidified on standing. The e.e.s were determined by
HPLC analysis of the crude mixture on a Daicel Chiral-
cel OD-H column (u=254 nm; flow rate 1 mL/min;
eluent: hexane/iso-PrOH 200:1, tR=19.57 min, tS=
18.18 min).
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