New P,N ligands with chiral nitrogen center: Applications in homogeneous catalysis

Article abstract of DOI:10.1016/S0022-328X(01)01148-2

In order to perform homogeneous asymmetric hydroformylation, hydrosilylation and Grignard cross-coupling reaction, we have developed a new family of P,N ligands derived from quincorine and quincoridine.

Full text of DOI:10.1016/S0022-328X(01)01148-2

Journal of Organometallic Chemistry 643–644 (2002) 98–104
www.elsevier.com/locate/jorganchem
New P,N ligands with chiral nitrogen center: applications in
homogeneous catalysis
Christine Saluzzo a, Je´re´my Breuzard a, Ste´phane Pellet-Rostaing a, Martial Vallet a,
Fre´de´ric Le Guyader b, Marc Lemaire a,*
a Laboratoire de Catalyse et Synthe`se Organique, UMR 5622, UCBL/CPE, Baˆtiment 308, 43 Boule6ard du 11 No6ember 1918,
69622 Villeurbanne Cedex France
b Rhodia, CR de Lyon, 85 A6enue des fre`res Perret, 69192 Saint Fons Cedex France
Received 12 June 2001; accepted 30 July 2001
Abstract
In order to perform homogeneous asymmetric hydroformylation, hydrosilylation and Grignard cross-coupling reaction, we
have developed a new family of P,N ligands derived from quincorine and quincoridine. © 2002 Elsevier Science B.V. All rights
reserved.
Keywords: Asymmetric catalysis; Aminophosphine; Aminophosphite; Hydroformylation; Hydrosilylation; Cross-coupling reaction
extensively studied [8]. This differentiation was ob-
served with hybrid ligands having a soft electron-donat-
1. Introduction
ing atom such as phosphorus and
a
hard
For the last three decades, chiral diphosphines have
played a crucial role in asymmetric catalytic reactions
as an alternative to the synthesis of optically pure
compounds either from the chiral pool or by resolution
of their racemic form.
electron-donating atom such as nitrogen [8b]. In this
context amino-phosphine, -phosphite, -phosphonite and
-phosphinite ligands were developed leading to com-
plexes used for asymmetric catalytic reactions, such as
allylic alkylation [9], hydrogenation [10], hydrosilyla-
tion [11], cross-coupling reaction [12], hydrogen transfer
reduction [13], and hydroformylation [14].
Cinchona alkaloids and their derivatives, relatively
cheap and readily available in both pseudo-enan-
tiomeric forms, have been extensively used. Partly due
to the bicyclic structure, they present at least four
stereogenic centers, including the N-chiral bridgehead.
This nitrogen atom is stabilized in the same way as the
phosphorus one in the BIPNOR [7], avoiding the rapid
inversion of usual amines. The use of transition metal
complexes of cinchona alcaloids and their derivatives in
catalysis is based on their bidentate nature which allows
optimal binding to transition metals [15]. They were
employed in catalytic asymmetric dihydroxylation [16]
and in various enantioselective phase transfer catalytic
reactions [17]. Nevertheless, their aminophosphorated
derivatives were less studied [18].
Kagan [1] and Knowles [2] have first developed
rhodium complexes of chiral chelating diphosphines,
DIOP and DIPAMP, respectively, for asymmetric hy-
drogenation. Other optically pure diphosphines have
been synthesized later on. Among them, BPPFA [3],
BPPM [4] or BINAP [5] have been involved in various
applications. For all these phosphines, the asymmetric
induction stands on the molecular skeleton [1,3–5] or
on the phosphorus atom itself [2]. Unfortunately, the
latter suffers from the relatively easy epimerization of
the phosphorus atom. More recently, Mathey [6] and
Imamoto [7] have reported the synthesis of a new chiral
ligand with an asymmetric non-epimerizable phospho-
rus atom.
In the 1990s, the concept which involves the asym-
metric induction by electronic differentiation has been
* Corresponding author. Tel.: +33-4-7243-1407; fax: +33-4-7243-
1408.
E-mail address: marc.lemaire@univ-lyon1.fr (M. Lemaire).
Hoffmann has described the transformation of
quinidine and quinine, two cinchona alkaloids, into
0022-328X/02/$ - see front matter © 2002 Elsevier Science B.V. All rights reserved.
PII: S0022-328X(01)01148-2

C. Saluzzo et al. / Journal of Organometallic Chemistry 643–644 (2002) 98–104
99
Scheme 1.
Scheme 2.
quincoridine 1a and quincorine 1b, respectively [19],
but, to the best of our knowledge, only phosphinite
derivatives of 1a and 1b were involved in asymmetric
hydrosilylation [18].
4b with diphenylphosphine in the presence of potassium
tert-butoxide in tetrahydrofuran according to the pro-
cedure of Kumada [21].
The second type of ligands keeps the unsaturation of
quincorine and quincoridine unchanged. It has been
prepared in two steps by treatment of quincoridine 1a
and quincorine 1b with p-toluenesulfonyl chloride in
dichloromethane, followed by phosphination. This lat-
ter reaction was carried out with diphenylphosphine in
tetrahydrofuran in the presence of potassium tert-bu-
toxide according to the Whitesides procedure [22]. Un-
der these conditions, ligands 6a and 6b were obtained,
respectively, with 100 and 50% overall yield (Scheme 2).
The non-hydrochlorinated ligands 6 were obtained in a
similar way from the mesylate derivative [23].
This paper deals with our efforts to synthesize and
evaluate new ligands containing P and N donor atoms
derived from quincoridine 1a ((2R,4S,5R)-2-hydrox-
ymethyl-5-vinyl-2-quinuclidine) and quincorine 1b
((2R,4S,5R)-2-hydroxymethyl-5-vinyl-2-quinuclidine),
having a stable chiral nitrogen center. Aminophosphite
and aminophosphine derivatives were tested in catalytic
asymmetric hydroformylation and aminophosphines
also in asymmetric reduction of CꢀO bonds (hydrosily-
lation) and in the asymmetric cross-coupling reaction
[20].
2.2. Aminophosphites synthesis
2. Synthesis of P,N ligands
Monophosphites 7 and 8 (Scheme 3) were prepared
from quincorine 1b, according to Takaya [24]. (R)- or
(S)-binol was transformed into its phosphochloridite by
means of phosphorous trichloride in the presence of
triethylamine, at −40 °C, then quincorine 1b was
added. Phosphites 7 and 8 were obtained in 27 and 41%
yield, respectively.
2.1. Aminophosphines synthesis
Commercially available quincoridine 1a and quin-
corine 1b, two aminoalcohols which differ only in the
position of the hydroxymethyl group (exo for 1a and
endo for 1b referred to the unsubstituted piperidine ring
(Scheme 1)) were transformed into their corresponding
saturated derivatives 2a and 2b by means of catalytic
hydrogenation in the presence of Pd/C. These com-
pounds were treated with hydrogen chloride in ethanol
to afford the corresponding ammonium chlorides. The
further transformation of the hydroxy group into a
chloromethyl moiety was performed with thionyl chlo-
ride in chloroform leading to products 3a and 3b. These
compounds were transformed into phosphines 4a and
Scheme 3.

100
C. Saluzzo et al. / Journal of Organometallic Chemistry 643–644 (2002) 98–104
Scheme 4.
3. Evaluation of P,N ligands in asymmetric catalysis
ety of functional groups in the substrate. In a pioneer-
ing work on asymmetric hydrosilylation, chiral
diphosphine ligands such as DIOP gave moderate enan-
tioselectivities for the asymmetric hydrosilylation of
ketone (DIOP–Rh:58–85% ee) [30]. Chiral nitrogen
ligands were tested later on. Most of them present an
oxazoline skeleton such as pyridinyloxazoline, bisoxa-
zoline. These nitrogen-containing ligands have given
rise to high levels of enantioselectivity [31]. More re-
cently, new ligands which present a combination of
oxazolinyl and phosphine structures were synthesized.
Their rhodium complexes could efficiently catalyze hy-
drosilylation of aromatic as well as aliphatic ketones
with excellent conversions and ees up to 90% [32].
Ligands 4 and 6 were used in asymmetric hydrosilyla-
tion of acetophenone using [RhCl(cod)]2 as precursor.
The reaction was carried out with diphenylsilane, at
−10 °C, in toluene for 72 h (Scheme 5, Table 2).
3.1. Hydroformylation
Hydroformylation is a very powerful synthetic tool
for the preparation of fine chemicals [25]. This reaction
is interesting if the chemoselectivity (hydroformylation
vs. hydrogenation), the regioselectivity (branched vs.
linear aldehyde) and the enantioselectivity are con-
trolled. For instance, with styrenic substrates, this reac-
tion provides
a straightforward method for the
preparation of branched aldehyde precursors of aryl-
propionic acids largely used in pharmaceutical applica-
tions (ibuprofen, naproxen) [26]. For this type of
reaction, chiral phosphites have received particular at-
tention for the last 20 years. Their rhodium complexes
showed high regioselectivities and enantioselectivities
for hydroformylation of arylsubstituted olefins [27]. We
carried out the asymmetric hydroformylation of styrene
leading to 2-phenylpropanal and 3-phenylpropanal,
with aminophosphite ligands 7 and 8, previously syn-
thesized from quincoridine (Scheme 4). Their corre-
sponding rhodium complexes were prepared in situ
from [Rh(cod)2]BF4 and the hydroformylation reaction
was performed in mild conditions [28] (Table 1).
After 18 h, the regioselectivities and enantioselectivi-
ties are identical for both complexes. The only differ-
ence observed concerns the activity. Rhodium complex
of ligand 8 (90% of conversion) was found to be more
efficient than that of ligand 7 (only 62% of conversion).
In both cases, b/n ratio is about 90/10. These results
show that this catalytic system is at least as regioselec-
tive as most of the catalytic systems described in the
literature but it is less enantioselective. The stereochem-
istry of the phosphite part of the ligand has a major
influence upon the absolute configuration. With (R)-
phosphite 7 (R)-aldehyde was formed, whereas the
(S)-phosphite 8 gave the (S)-aldehyde. For ligands 4a
and 4b (runs 3 and 4), after one week, lower conver-
sions but no enantiomeric excess (ee) are observed,
although b/n ratios are similar.
Table 1
Hydroformylation of styrene
a
Run Ligand L*
Conversion a (%) b/n
ee a (%)
(configuration)
1
2
3
4
7
8
4a
4b
62
88/12
89/11
93/7
16 (R)
13 (S)
0
0
90
42 b
35 b
90/10
a Determined by GC analysis on a Supelco b-DEX™ 225, (60
m×0.25 mm) chiral column.
b After one week.
Scheme 5.
Table 2
Hydrosilylation of acetophenone
a
Run Ligand
Conversion (%)
ee a (%) (configuration)
3.2. Asymmetric hydrosilylation
1
2
3
4
4a
4b
6a
6b
96
89
73
42
54 (R)
1 (S)
54 (R)
4 (S)
Asymmetric hydrosilylation is a useful synthetic tool
for the production of chiral amines and alcohols [29].
This reaction provides an alternative route to hydro-
genation, avoiding pressurized hydrogen. Moreover,
hydrosilylation is known to be tolerant towards a vari-
a Determined by GC analysis on a Supelco b-DEX™ 225, (60
m×0.25 mm) chiral column.

C. Saluzzo et al. / Journal of Organometallic Chemistry 643–644 (2002) 98–104
101
According to the literature, we supposed that, for the
cross-coupling reaction, aminophosphine ligands 4 and
6 acted as bidentate ligands [4,35]. In this case, the
presence of a vinyl group has an effect upon both the
enantioselectivity and the activity. With unsaturated
ligand 6a, a decrease of both the ee and the yield was
observed (runs 1 and 4). With the more hindered exo
ligand 4a (run 1), selectivity is lower than that observed
with the endo 4b (run 2). Compared to hydrosilylation,
the steric hindrance between the phosphine and the
ethyl groups, in syn position to each other, has the
opposite effect on the selectivity. The enantioselectivity
was improved at low temperature: 86% ee at 0 °C (run
3) and 75% ee at 25 °C (run 2).
Scheme 6.
Table 3
Asymmetric nickel-catalyzed cross-coupling of 1-phenylethylmagne-
sium chloride with vinyl bromide
Run Ligand
Temperature (°C)
Yield a (%)
ee a (%)
1
2
3
4
4a
4b
4b
6a
25
25
0
80
65
50
45
65 (−)
75 (+)
86 (+)
52 (−)
25
In terms of enantioselectivity, nickel systems could be
considered as one of the most efficient. The highest
enantioselectivity (88% ee) has been obtained by means
of the homomethphos ligand [36].
a Determined by GC analysis on a Supelco b-DEX™ 225, (60
m×0.25 mm) chiral column.
The reaction was carried out with free nitrogen lig-
ands 4 and 6. Similar enantiomeric excesses were ob-
served with 4a and 6a and with 4b and 6b. The presence
or the absence of the vinyl group in the structure of the
ligand has no influence upon the enantioselectivity
(runs 1, 3 and 2, 4, respectively). But the position of the
phosphine group plays a crucial role upon the enan-
tioselectivity. Ligands 4a and 6a, having their phos-
phine group in the exo position, showed better
enantioselectivities (54%, runs 1 and 3) than those
presenting this group in the endo position (4b and 6b),
which gave rise to an almost racemic product (runs 2
and 4).
This difference should be attributed to the cumula-
tive effect of the chiralities of 4a and 6a while those of
4b and 6b lead to the opposite effect [33]. Another
possible explanation for the difference in enantioselec-
tivity is the steric hindrance of the exo compounds,
because the vinyl (or ethyl), and the phosphine moieties
are in syn position to each other. Concerning the
conversions, they are better with exo ligands 4a or 6a
than with the endo ones 4b or 6b.
4. Conclusions
Aminophosphines 4 and 6 and aminophosphites 7
and 8 are readily prepared from quincorine and quin-
coridine. This paper shows that rhodium complexes of
aminophosphines 4 and 6 can be used in various asym-
metric catalytic reactions.
In the case of hydroformylation, the regioselectivity
obtained with ligands 7 and 8 is about the same as the
one reported in the literature, but the enantioselectivity
remains low.
Best results were achieved for hydrosilylation and
Grignard cross-coupling reactions. For the latter, the
best enantioselectivities were obtained with the endo
aminophosphine 4b nickel complex. This system was
shown to be among the best ever described in the
literature, using the same conditions.
Other substrates and catalytic reactions have to be
tested in order to reveal the scope and the limitations of
these new catalytic systems. The commercial availability
of the two aminoalcohols allows their use as building
blocks in order to obtain a large variety of ligands,
whose nitrogen chirality could be controlled. The work
presented in this paper could thus be considered only as
a starting point.
3.3. Asymmetric Grignard cross-coupling reaction
One of the first uses of nitrogen-containing ligands is
in the Grignard cross-coupling of organometallic
reagents with alkenyl or aryl halide. The metal precur-
sors used are nickel or palladium complexes. With P,N
ligands derived from aminoacids, good results were
obtained [34].
5. Experimental
5.1. General
We performed the Grignard cross-coupling reaction
of 1-phenylethylmagnesium chloride with vinylbromide
in the presence of nickel chloride and aminophosphines
4 and 6a (Scheme 6). Aminophosphine 6a was neutral-
ized prior to use. Results are presented in Table 3.
Quincoridine and quincorine were purchased from
Buchler GmbH and all other reagents from Aldrich.
Polarimetric measurements were performed on a
Perkin–Elmer 241 instrument, at ambient temperature,
at 589 nm, and at a concentration of grams per 100 ml.

102
C. Saluzzo et al. / Journal of Organometallic Chemistry 643–644 (2002) 98–104
Elemental analyses and mass spectra (electrospray: HP
5989/MS Engine) were carried out by the CNRS (Ser-
vice Central d’Analyse—De´partement d’Analyse Ele´-
mentaire) Solaize, France. Infrared spectra were
recorded on a Mattson 5000 FT apparatus (w in cm−1).
1H-, 13C-, and 31P-NMR spectra were recorded with a
Bruker AM200 (1H, 200 MHz; 13C, 50 MHz; and 31P,
81 MHz) using TMS as internal standard (1H-, 13C-
NMR) or phosphoric acid 85% in D2O as external
standard (31P-NMR) and CDCl3 as solvent. Conver-
sions and enantiomeric excesses were determined by
GC analysis on a Supelco b-DEX™ 225, (60 m×0.25
mm) chiral column, using a Shimadzu GC 14A appara-
tus equipped with FID connected to a Schimadzu
CR6A integrator.
5.2.1.3. Synthesis of phosphine 4a or 4b. Under argon,
diphenylphosphine (0.4 ml, 2.2 mmol) was added to a
suspension of potassium tert-butoxide (11.5 mmol) in
anhydrous THF (20 ml). After 30 min of stirring at r.t.,
the chlorhydrate 3a (0.5 g, 2.2 mmol) was added to the
red solution. The reaction mixture was refluxed until
the red color disappeared. After removal of the solvent,
HCl 10% (10 ml) was added to the residue. The
aqueous layer was extracted with toluene (30 ml), neu-
tralized with NaOH 10% (20 ml), and then washed with
toluene. The combined organic layers were rinsed with
brine and dried with Na2SO4. The solvent was evapo-
rated and a yellow oil was obtained. Purification by
filtration through neutral alumina led to the phosphite
4a (yield: 24%) as a colorless oil. The same procedure
was used for 4b (yield: 24%).
4a: [h]2D5= −16.2 (c=1.0, THF). ES-MS: 338.2
([M+H]+). 31P{1H}-NMR: l −22.0. 1H-NMR: l 0.87
(t, 3H), 1.0–1.8 (m, 9H), 2.0–3.0 (m, 6H), 7.2–7.6 (m,
10H), 13C{1H}-NMR: l 12.1; 25.8; 26.5 (d, JCP=5 Hz),
27.3, 29.6 (d, JCP=7 Hz), 35.1 (d, JCP=12 Hz), 37.9,
49.1 (d, JCP=11 Hz), 53.4 (d, JCP=17 Hz), 128.3,
128.4, 128.5, 133.0, 133.1. 4b: [h]2D5= +15.9 (c=1.0,
THF). ES-MS: 338.2 ([M+H]+). 31P{1H}-NMR: l
−22.0. 1H-NMR: l 0.75 (t, 3H), 1.0–3.2 (m, 15H),
7.2–7.7 (m, 10H). 13C{1H}-NMR: l 11.9, 25.7, 26.9 (d,
5.2. Synthesis of P,N ligands
5.2.1. Aminophosphines 4
5.2.1.1. Synthesis of saturated compounds 2a and 2b. A
suspension of 10% Pd/C (0.9 mmol) and quincoridine
1a or quincorine 1b (6 mmol) in THF (60 ml) was
stirred under hydrogen (1 bar) during 8 h. The resulting
solution was filtered over celite 545 and the solvent was
removed. Pure compounds 2a and 2b were obtained in
100% yields. They present the same spectral data as
those obtained by Hoffman [37].
JCP=5 Hz), 29.2, 29.7 (d, JCP=7 Hz), 37.4 (d, JCP=
12 Hz), 37.9, 48.7 (d, JCP=11 Hz), 48.9 (d, JCP=17),
128.4, 128.5, 128.6, 132.7, 132.9.
5.2.1.2. Synthesis of chloride 3a or 3b. A solution of
alcohol 2a (0.9 g, 5.3 mmol) in EtOH (10 ml) was
carefully added to an excess of HCl (37%) (4 ml). The
reaction mixture was stirred for 30 min at room tem-
perature (r.t.), and then the solvent and the excess of
acid were removed under reduced pressure. To the
chlorhydrate dissolved in CHCl3 (10 ml), thionyl chlo-
ride (1 ml, 2.5 equivalents) was added at 0 °C. After
the reaction mixture was refluxed for 2 h, the solvent
was removed, at r.t. under vacuum. The residue was
dissolved in EtOH (2 ml) and the dropwise addition of
ether gave crystallization. The crystals were filtered and
dried under vacuum at 50 °C over P2O5 (yield: 56%).
The same procedure was used for 3b (Yield 81%).
3a: ES-MS (ES+): 188.0 ([M+H])+), 411.2 ([2M+
HCl+H]+), (ES−): 258.0 ([M+Cl]−), 296.0 ([M+
5.2.2. Aminophosphines 6
5.2.2.1. Synthesis of tosylates 5a and 5b. At 0 °C, tosyl
chloride (1.53 g, 8.02 mmol) was added to a solution of
quincorine 1a or quincoridine 1b (1 g, 6 mmol) in
CH2Cl2 (20 ml). The reaction was allowed to stir for 6
h at 0 °C. The reaction mixture was washed with a
saturated aqueous solution of NaHCO3, and then with
water. The organic phase was dried over MgSO4. After
removal of the solvent, an oily residue was isolated.
This latter compound was dissolved in a solution of
acetyl chloride (0.85 ml) in EtOH–ether (0.84/20 ml).
After 1 h of stirring, the white solid formed was filtered
over celite, and then washed with ether (yield: 74%).
The same procedure was used for 5b (yield: 100%).
1
5a: [h]D= +86.58 (c=1.57, CH2Cl2). H-NMR: l
1
HCl+Cl]−), 483.0 (2M+Cl]−). H-NMR: l 0.92 (t,
1.6–1.8 (m, 2H), 1.8–1.9 (m, 2H), 1.9–2.0 (m, 1H),
2.30 (s, 3H), 2.5–2.6 (m, 1H), 2.8–3.5 (m, 4H), 3.6–3.8
(m, 1H), 4.26 (d, 1H, 3J=10.3 Hz), 4.52 (d, 1H,
3
3H, J=7.1 Hz), 1.3–2.2 (m, 8H); 2.7–4.4 (m, 7H),
12.28 (br s, 1H). 13C{1H}-NMR: l 11.4, 23.9, 24.5,
24.8, 24.9, 35.2, 42.7, 48.5, 48.6, 57.5. 3b: ES-MS
(ES+): 188.0 ([M+H])+), 411.2 ([2M+HCl+H]+),
(ES−): 258.0 ([M+Cl]−), 296.0 ([M+HCl+Cl]−),
3J=10.3 Hz), 4.96 (d, 1H, J=16.6 Hz), 5.04 (d, 1H,
3
3J=9.9 Hz), 5.75 (ddd, 1H, 3J=16.6, 9.9, 5.9 Hz), 7.24
(d, 2H, 3J=7.7 Hz), 7.71 (d, 2H, 3J=7.7 Hz), 11.80 (br
s, 1H). 13C{1H}-NMR: l 21.9, 22.1, 23.7, 27.2, 37.0,
47.6, 49.1, 56.0, 67.8, 118.2, 128.5, 130.6, 132.2, 136.8,
145.6. IR (KBr, cm−1): w 3420, 2900, 2500, 1680, 1590,
1450, 1400, 1360, 1290, 1170, 1120, 1120, 1090, 1070,
1
3
483.0 ([2M+Cl]−). H-NMR: l 0.82 (t, 3H, J=7.1
Hz), 1.4–2.2 (m, 8H), 2.8–4.0 (m, 7H), 11.89 (br s, 1H).
13C{1H}-NMR: l 11.5, 24.3, 24.6, 26.6, 34.9, 41.6, 43.5,
55.6, 57.4.

C. Saluzzo et al. / Journal of Organometallic Chemistry 643–644 (2002) 98–104
103
990, 930, 910, 880, 820, 790, 760, 710, 660. Mass
[M+H]+: 322.14760. Elemental analysis: Calc.: C,
56.85; H, 6.79; Cl, 9.99; N, 4.01; O, 13.37; S, 8.87.
Found: C, 56.76; H, 6.95; Cl, 9.72, N, 3.91; O, 13.66; S,
the chlorhydrate formed was removed by decantation,
and the ethereal solution was concentrated under vac-
uum. The pure compound was obtained by precipita-
tion with pentane. After filtration, the phosphite 7 was
obtained in 27% yield. Phosphite 8 was obtained in the
same way, using (S)-BINOL in 41% yield.
1
8.96%. 5b: H-NMR: l 1.7–1.8 (m, 1H), 1.8–2.2 (m,
4H), 2.39 (s, 3H), 2.6–2.7 (m, 1H), 3.0–3.7 (m, 5H),
4.32 (dd, 1H, 2J=11.7, 3J=4.4 Hz), 4.59 (dd, 1H,
7: [h]D= −22.9 (c=1.0, THF). 31P{1H}-NMR: l
3
3
1
2J=11.7, J=3.1 Hz), 5.13 (d, 1H, J=17.6 Hz), 5.22
145. H-NMR: l 1.0–4.0 (m, 13H), 4.3–4.6 (m, 1H),
(d, 1H, 3J=10.7 Hz), 5.85 (ddd, 1H, 3J=17.6, 10.7, 6.6
5.6–5.9 (m, 2H), 7.0–8.0 (m, 12H). Elemental analysis:
Calc.: C, 74.83; H, 5.86; N, 2.91; O 9.97; P, 6.43.
Found: C, 74.71; H, 5.77; N, 3.30; O, 9.70; P, 6.32%. 8:
[h]D= +23.4 (c=1.0, THF). 31P{1H}-NMR: l 145.
1H-NMR: l 1.0–4.0 (m, 13H), 4.3–4.6 (m, 1H), 5.6–
5.9 (m, 2H), 7.0–8.0 (m, 12H). IR (KBr, cm−1): 3056,
2995, 1620, 1589, 1463, 1431, 1359, 1326, 1259, 1218,
1154, 1070, 978, 949, 866, 771, 750, 694, 646, 598, 556,
527.
3
3
Hz), 7.32 (d, 2H, J=8.3 Hz); 7.78 (d, 2H, J=8.3
Hz), 12.21 (br s, 1H). 13C{1H}-NMR: l 21.9, 22.1, 24.3,
26.9, 36.8, 43.0, 53.7, 55.9, 68.2, 117.8, 128.4, 130.6,
132.2, 137.3, 146.1. IR (cm−1): w 3410, 2900, 2500,
1680, 1590, 1450, 1360, 1290, 1170, 1120, 1120, 1090,
1070, 990, 930, 910, 880, 820, 790, 760, 710. Mass
[M+H]+: 322.147.
5.2.2.2. Synthesis of phosphines 6a and 6b. Under argon,
to a stirred suspension of potassium tert-butoxide (0.74
g, 6.6 mmol) in anhydrous THF (19 ml) was added
diphenylphosphine (0.542 ml, 3.1 mmol). After 5 min at
r.t., the tosylate 5a (0.81 g, 2.5 mmol) was added to the
reaction mixture, which was refluxed during 16 h. Hex-
ane (36 ml) was then added, at r.t. and the organic layer
was washed with an aqueous solution of NaOH 10%
(twice with 8.5 ml), and then with brine (10 ml).
Compound 6a was isolated in its chlorhydrate form
(yield: 100%). The same procedure was used for 6b
(yield: 68%).
5.3. Asymmetric catalysis
5.3.1. Hydroformylation of styrene
Under argon, styrene (18 mmol) was added to a
solution of [Rh(cod)2]BF4 (18 ml) and ligand 7 or 8 (36
ml) in anhydrous CH2Cl2 (4 ml). After 18 h under H2
(PH : 20 bar) and CO (PCO: 20 bar), the autoclave was
2
vented.
5.3.2. Hydrosilylation
6a: [h]D= +93.0 (c=1.65, CHCl3). Mass [M+H]+:
336.188. 31P-NMR (D2O): l −24.8. 1H-NMR (D2O): l
1.6–2.9 (m, 7H), 3.1–3.5 (m, 6H), 5.1–5.3 (m, 2H),
5.7–6.0 (m, 1H), 7.2–7.8 (m, 10H), 12.15 (br s, 1H).
Elemental analysis: Calc.: C, 71.09; H, 7.27; Cl, 9.54; N,
3.72; P, 8.31. Found: C, 58.65; H, 6.47; Cl, 14.03;N,
3.18; P, 7.03%. 6b: [h]D= −48.96 (c=1.26, CHCl3).
Mass [M+H]+: 336.188. 31P-NMR (D2O): l −24.7.
1H-NMR (D2O): l 1.9–3.9 (m, 13H), 5.0–5.2 (m, 2H),
5.7–5.9 (m, 1H), 7.4–7.8 (m, 10H), 12.10 (br s, 1H).
Elemental analysis: Calc: C, 64.71; H, 6.91; Cl, 17.36;
N, 3.43; P, 7.59. Found: C, 64.64; H, 6.67; Cl, 17.03; N,
3.30; P, 7.30%.
Under argon, to a solution of [RhCl(cod)]2 (0.02
mmol) and ligand 4a, 4b, 6a or 6b (0.08 mmol) in
toluene (5 ml), acetophenone (4 mmol) was added.
After cooling the solution at −10 °C, diphenylsilane
(4.4 mmol) was introduced. The resulting mixture was
maintained and stirred at −10 °C for 72 h, and then
0.5 ml of this solution was poured into a solution of
p-toluene sulfonic acid (some crystals) in anhydrous
methanol (2 ml).
5.3.3. Grignard cross-coupling reaction
Under argon, at −40 °C, vinyl bromide (0.75 ml, 10
mmol) was added to a solution of phosphine 4a, 4b or
6a (0.08 mmol) with NiCl2 (0.08 mmol) in anhydrous
Et2O (2 ml). Freshly prepared 1-phenyl magnesium
chloride 1 M (5 mmol) was then added. The mixture
was kept at r.t. for 12 h. After hydrolysis by means of
a saturated aqueous solution of NH4Cl and extraction
with Et2O, the organic layer was rinsed with brine and
then dried over MgSO4.
5.2.3. Synthesis of phosphites 7 and 8
Under argon, at −40 °C, a solution of PCl3 (210 ml,
2.4 mmol) and Et3N (0.5 ml, 4.8 mmol) in anhydrous
toluene (5 ml) was added dropwise to a solution of
(R)-BINOL (690 mg, 2.4 mmol) first dissolved at 60 °C
in anhydrous toluene (40 ml). The reaction mixture was
allowed to stir for 2 h at r.t. The triethylamine hydro-
chloride formed was removed by filtration through
alumina. After evaporation of the solvent, the
chlorophosphite was dissolved in anhydrous ether, and
cooled at 0 °C. To this mixture, quincoridine 1b (0.4 g,
2.4 mmol) in solution with Et3N (0.5 mL, 4.8 mmol)
was added dropwise. After one night of stirring at r.t.,
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