Totally diastereoselective synthesis of a new chiral quinoline diazaphospholidine ligand and its derivatives

Article abstract of DOI:10.1016/S0040-4039(02)00691-3

QUIPHOS-PN5, a new stable P,N ligand with a stereogenic phosphorus centre was synthesised in two steps from 8-bromoquinoline (61% yield). Its structure and its bidentate chelating ability was confirmed by the X-ray structure of a palladium(II) complex with this ligand. P(V) derivatives of QUIPHOS-PN5 were then easily obtained in excellent yields (85-100%).

Full text of DOI:10.1016/S0040-4039(02)00691-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 4025–4028
Totally diastereoselective synthesis of a new chiral quinoline
diazaphospholidine ligand and its derivatives
Guillaume Delapierre, Mathieu Achard and Ge´rard Buono*
ENSSPICAM, UMR 6516 ‘Synthe`se, Catalyse et Chiralite´’, Av. Escadrille Normandie Niemen, F-13397 Marseille Cedex 20,
France
Received 8 April 2002; accepted 10 April 2002
Abstract—QUIPHOS-PN5, a new stable P,N ligand with a stereogenic phosphorus centre was synthesised in two steps from
8-bromoquinoline (61% yield). Its structure and its bidentate chelating ability was confirmed by the X-ray structure of a
palladium(II) complex with this ligand. P(V) derivatives of QUIPHOS-PN5 were then easily obtained in excellent yields
(85–100%). © 2002 Elsevier Science Ltd. All rights reserved.
Chiral organophosphorus compounds found broad
applications in asymmetric catalysis as ligands of tran-
sition metals1 or as catalysts.2 By adding a coordinating
nitrogen atom to these structures, we obtained hybrid
bidentate and unsymmetrical P,N ligands, interesting
because of the different electronic properties of phos-
phorus and nitrogen atom which might enhance both
the catalyst activity and the enantioselectivity.3 Oxi-
dised phosphorus (Pl5s4) have demonstrated their
QUIPHOS-PN5 2 was easily obtained in two steps
efficiency, mainly as catalyst in asymmetric catalysis.2,4
from 8-bromoquinoline 3 in 61% overall yield (Scheme
1). 8-Lithioquinoline generated in situ with sec-butyl-
We previously described the synthesis of QUIPHOS 1,
lithium was trapped by chlorobis(dimethylamino)phos-
a stable P,N six-membered ring chelate ligand with a
phine11 to form 8-(bis(dimethylamino)phosphine)-
stereogenic phosphorus atom.5 This ligand is efficient in
quinoline 4.12 A totally diastereoselective exchange
asymmetric catalysis, associated to palladium in allylic
reaction between 4 and (S)-anilinomethylpyrrolidine5 5
alkylation (ee up to 85%)6 and allylic amination (ee up
afforded QUIPHOS-PN5 2 characterised as the ther-
93%)7 or to copper in Diels–Alder reaction (ee up to
modynamic anti-diastereomer.13
>98%)8 and conjugate addition (ee up to 61%).9
The chiral oxide diazaphospholidine 6 and the corre-
sponding phosphine sulphide 7 were prepared, respec-
tively, by action of t-butyl hydroperoxide and sulphur
with 2 in 100 and 95% chemical yields. By the same
way, the reaction of phenyl azide with 2 leads to the
chiral iminodiazaphospholidine14 8 in 85% chemical
yield. This new compound has two different basic
amine sites closely positioned and may accept a proton
between the nitrogens.
To evaluate the electronic differentiation and the bite
angle effects10 of the P,N bidentate ligand in different
asymmetric catalytic reactions catalysed by transition
metal complexes, we report in this letter an efficient
synthesis of 2. This ligand, called QUIPHOS-PN5 is an
analogue of 1 and is able to form five-membered ring
chelate. Moreover, the stability of the ligand was
expected to increase by replacing the hydrolysable PꢀO
bond by a stable PꢀC one.
Complex 9 was obtained in quantitative yield by mixing
an equimolar amount of PdCl2(CH3CN)2 and ligand 2
in methylene chloride (Scheme 2). Crystallisation from
toluene afforded 9 as pale brown crystals stable to air
and moisture. X-Ray diffraction analysis confirms the
chelating ability of ligand 2 towards palladium and the
Keywords: chiral bidentate P,N ligand; phosphine oxide; phosphine
sulphide; iminophosphorane; palladium complex.
* Corresponding author. Tel.: +33 (0) 491288681; fax: +33 (0)
491282742; e-mail: buono@spi-chim-u-3mrs.fr
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00691-3

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G. Delapierre et al. / Tetrahedron Letters 43 (2002) 4025–4028
Scheme 1.
,
Scheme 2. Structure of 9, showing labelling scheme. Selected bond distances (A): Pd1ꢀCl1=2.30 (12), Pd1ꢀCl2=2.40 (12),
Pd1ꢀP1=2.18 (13), Pd1ꢀN1=2.07 (3). Selected angle (°): P1ꢀPd1ꢀN1=85.8. Selected dihedral angles (°): Cl2ꢀPd1ꢀCl1ꢀP1=178.6,
Cl2ꢀPd1ꢀCl1ꢀN1=−177.8.
Sp absolute configuration of the phosphorus (s3l3)
atom.15 A classical square planar geometry is observed
for this Pd(II) complex (bite angle:16 P1ꢀPd1ꢀN1=85.8,
taken up in a mixture of Et2O (100 mL) and a solution
of EDTA/0.5N NaOH (1:4.2, 20 mL). After stirring for
5 min, the two layers were separated. The organic layer
was washed with water (2×10 mL), dried (Na2SO4),
filtered and evaporated to give 4 as an orange oil (2.35
Cl2ꢀPd1ꢀCl1ꢀP1=178.6
and
Cl2ꢀPd1ꢀCl1ꢀN1=
−177.8°). Moreover, the PdꢀCl bond lengths are signifi-
cantly different from one another, the chlorine atom
trans to phosphorus displaying the expected longer
1
g) and enough pure for the synthesis of 2, H NMR
(CDCl3): l (ppm, J Hz) 8.76 (dd, 1H, J 1.8, 3.9), 7.90
(dd, 1H, J 1.5, 8.1), 7.70 (ddd, 1H, J 1.8, 3.0, 7.2), 7.54
(dd, 1H, J 1.5, 8.1), 7.35 (dt, 1H, J 1.2, 6.9), 7.16 (dd,
1H, J 4.2, 8.1), 2.58 (d, 12H, J 9.9); 13C NMR (CDCl3):
l (ppm, J Hz) 149.0 (d, J 1.1), 148.8, 139.8 (d, J 12.1),
135.6 (d, J 1.7), 131.8 (d, J 5.2), 127.7 (d, J 1.7), 127.6
(d, J 1.1), 125.8, 120.4, 41.5 (d, J 17.8); 31P NMR
(CDCl3): l (ppm) 98.3.
,
distance (Pd1ꢀCl2=2.40 (12) A) as compared to its
,
partner trans to nitrogen (Pd1ꢀCl1=2.30 (12) A). This
is the expression of the higher trans influence of the
phosphine ligand.17
In conclusion, we have reported the easy synthesis of a
new stable chiral P,N ligand and three of its derivatives
in good to excellent yields. The optimisation of the
synthesis of the key intermediate 4 allows us to modify
the nature of the chiral auxiliary. Applications of the
four new compounds 2, 6–8 as ligands or catalysts in
asymmetric catalysis are in progress.
(2R,5S)-3-Phenyl-2-(8-quinolyle)-1,3-diaza-2-phosphabi-
cyclo-[3.3.0]-octane 2:
A
solution of (S)-anili-
nomethylpyrrolidine 5 (1.42 g, 8.08 mmol) and 4 (2 g,
8.08 mmol) in dry toluene (4 mL) was refluxed for 2 h
under argon and then evaporated. The residue was
taken up in dry Et2O (13 mL), filtered and washed with
Et2O to give 2 as a white powder (1.63 g, 61% from 3),
mp 191°C, [h]2D0=−486.5 (c 0.5, CH2Cl2), 1H NMR
(CDCl3): l (ppm, J Hz) 8.80 (dd, 1H, J 1.2, 3.9), 7.92
(d, 1H, J 8.1), 7.57 (d, 1H, J 8.1), 7.23–7.36 (m, 1H),
7.18–7.23 (m, 2H), 7.01 (t, 2H, J 7.8), 6.72 (d, 2H, J
7.8), 6.57 (t, 1H, J 7.4), 3.78–3.86 (m, 1H), 3.55 (t, 1H,
J 8.0), 3.19–3.39 (m, 2H), 3.02 (td, 1H, J 2.1, 8.6),
1.61–1.96 (m, 4H), 13C NMR (CDCl3): l (ppm, J Hz)
Experimental
8-(Bis(dimethylamino)phosphine)quinoline
4:
Under
argon, sec-BuLi (1.1N in hexanes, 8.7 mL, 9.61 mmol)
was dropwise added to a cooled solution (−78°C) of
8-hydroxyquinoline (2 g, 9.61 mmol) in dry THF (25
mL). After stirring for 5 min, a solution of ClP(NMe2)2
(1.78 g, 11.54 mmol) in THF (2 mL) was added and the
solution was allowed to warm to rt. After stirring 12 h
at rt, the mixture was evaporated and the residue was

G. Delapierre et al. / Tetrahedron Letters 43 (2002) 4025–4028
4027
1
149.9 (d, J 15.9), 149.7 (d, J 1.7), 147.0 (d, J 15.4),
139.2 (d, J 26.0), 136.0 (d, J 1.1), 130.4 (d, J 2.8), 129.0,
128.9 (d, J 1.2), 128.4 (d, J 1.1), 126.0, 121.0, 117.5,
115.2 (d, J 13.2), 63.9 (d, J 8.5), 53.8 (d, J 4.8), 52.4 (d,
J 30.0), 30.5, 25.5 (d, J 6.0), 31P NMR (CDCl3): l
(ppm) 97.4. Anal. calcd for C20H20N3P: C, 72.06; H,
6.05; N, 12.60. Found: C, 72.14; H, 6.09; N, 12.60%.
(c 0.5, CH2Cl2), H NMR (CDCl3): l (ppm, J Hz) 8.86
(dd, 1H, J 1.7, 4.2), 8.71 (d, 1H, J 7.5), 8.40 (ddd, 1H,
J 1.5, 7.0, 15.6), 8.13 (td, 1H, J 2.0, 8.3), 7.82 (td, 1H,
J 1.2, 8.0), 7.48 (dd, 1H, J 2.2, 8.0), 7.43 (dd, 1H, J 4.2,
8.3), 7.11–7.22 (m, 3H), 7.0 (td, 2H, J 1.0, 7.3), 6.85 (m,
1H), 6.53 (td, 1H, J 1.0, 7.3), 6.34 (dt, 2H, J 0.7, 7.5),
4.17–4.38 (m, 1H), 3.12–3.30 (m, 1H), 2.81–3.03 (m,
3H), 1.38–1.70 (m, 4H), 13C NMR (CDCl3): l (ppm, J
Hz) 150.2, 148.8, 147.2 (d, J 7.2), 141.6, 138.1, 136.3 (d,
J 6.9), 132.9–130.0 (d, J 148.7), 132.3 (d, J 3.0), 129.7,
129.4, 128.6 (d, J 9.9), 127.1, 126.9, 121.8 (d, J 3.0),
119.25 (d, J 6.9), 117.0, 112.9, 58.6 (d, J 3.8), 49.4, 47.3
(d, J 4.9), 30.6 (d, J 5.7), 25.6 (d, J 6.5), 31P NMR
(CDCl3): l (ppm) 18.2.
(2R,5S)-3-Phenyl-2-(8-quinolyle)-1,3-diaza-2-phosphabi-
cyclo-[3.3.0]-octane-2-oxide 6: Under argon, tBuOOH
(5.5N solution in toluene, 164 mL, 0.9 mmol) was
carefully added to an ice cooled solution of 5 (0.301 g,
0.9 mmol) in dry toluene (10 mL). After stirring for 30
min at 0°C, the mixture was evaporated to give 6 as a
brown solid (0.315 g, 100%), mp 193°C, [h]2D0=−202 (c
1
0.5, CH2Cl2), H NMR (CDCl3): l (ppm, J Hz) 8.76
[PdCl2(QUIPHOS-PN5)] 9: Under argon, 5 (55.39 mg,
0.166 mmol) was added to a solution of PdCl2(MeCN)2
(43.10 mg, 0.166 mmol) in dry dichloromethane (5 mL).
The solution was stirred for 10 min, then evaporated to
give 9 as a yellow solid (84.9 mg, 100%), mp 253°C,
[h]2D0=+180 (c 0.1, CH2Cl2), 1H NMR (CDCl3): l
(ppm, J Hz) 10.45 (d, 1H, J 5.3), 8.51 (d, 1H, J 8.3),
8.06–8.18 (m, 2H), 7.66–7.80 (m, 2H), 7.09–7.12 (m,
4H), 6.91–6.99 (m, 1H), 4.25–4.46 (m, 2H), 3.78–4.10
(m, 2H), 2.99–3.17 (m, 1H), 2.31–2.52 (m, 1H), 1.95–
2.21 (m, 3H), 31P NMR (CDCl3): l (ppm) 103.3.
(dd, 1H, J 1.7, 4.3), 8.53 (ddd, 1H, J 1.5, 7.0, 15.6), 7.86
(td, 1H, J 2.0, 8.3), 7.69 (td, 1H, J 1.2, 8.3), 7.41 (ddd,
1H, J 3.0, 7.0, 8.0), 7.16 (dd, 1H, J 4.0, 8.0), 6.92–7.05
(m, 4H), 6.61 (tt, 1H, J 1.5, 6.8), 4.07–4.28 (m, 2H),
3.79–3.97 (m, 1H), 3.40–3.48 (m, 1H), 2.81–2.99 (m,
1H), 1.66–2.12 (m, 4H); 13C NMR (CDCl3): l (ppm, J
Hz) 150.5, 148.6, (d, J 5.7), 142.7 (d, J 7.2), 139.0 (d, J
8.4), 136.6 (d, J 1.9), 133.6–130.4 (d, J 162.5), 132.6 (d,
J 3.0), 129.1, 128.6 (d, J 9.5), 126.1 (d, J 15.7), 121.56,
120.18, 116.2 (d, J 4.6), 60.0 (d, J 6.1), 50.1 (d, J 15.7),
45.8, 34.1, 27.0 (d, J 2.6); 31P NMR (CDCl3): l (ppm)
27.7. Anal. calcd for C20H20N3OP: C, 68.76; H, 5.77; N,
12.03. Found: C, 68.87; H, 5.77; N, 11.87%.
Acknowledgements
(2R,5S)-3-Phenyl-2-(8-quinolyle)-1,3-diaza-2-phosphabi-
cyclo-[3.3.0]-octane-2-sulphide 7: Under argon at rt, sul-
phur (28.8 mg, 0.899 mmol) was added to a solution of
5 (0.3 g, 0.899 mmol) in dry toluene (10 mL). This
solution was stirred for 30 min, then evaporated and
the residue was purified by column chromatography on
silica gel (petroleum ether/ethyl acetate, 3:2) to give 7 as
a red-brown solid (312 mg, 95%), mp 220°C, [h]2D0=
We thank Dr. Michel Giorgi for his kind assistance
with X-ray analysis of compound 9. We are grateful to
CNRS for its financial support. M.A. acknowledges
MENRT for a doctoral fellowship.
1
+7.14 (c 0.5, CH2Cl2), H NMR (CDCl3): l (ppm, J
References
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3.54 (m, 1H), 2.73–2.92 (m, 1H), 1.62–2.19 (m, 4H); 13
C
NMR (CDCl3): l (ppm, J Hz) 150.3, 147.5 (d, J 3.4),
142.7 (d, J 7.2), 140.7 (d, J 16.1), 136.8, 136.1–133.7 (d,
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52.5 (d, J 12.6), 46.8 (d, J 3.8), 33.8 (d, J 1.9), 27.4 (d,
J 3.4), 31P NMR (CDCl3): l (ppm) 75.9. Anal. calcd for
C20H20N3PS: C, 65.74; H, 5.52; N, 11.50. Found: C,
65.69; H, 5.47; N, 11.29%.
(2R,5S)-3-Phenyl-2-(8-quinolyle)-1,3-diaza-2-phosphabi-
cyclo-[3.3.0]-octane-2-phenylimino 8: Under argon,
phenyl azide (63 mg, 0.531 mmol) was added to an ice
cooled solution of 5 (154 mg, 0.469 mmol) in toluene (5
mL). The solution was stirring at rt for 30 min, then at
60°C overnight. The solvent was evaporated and the
residue was purified by column chromatography on
silica gel (petroleum ether/ethyl acetate, 2:8) to afford 8
as a yellow solid (192 mg, 85%), mp 80°C, [h]2D0=+3.5
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coordinated to cationic p-allyl palladium.5
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