Synthesis and characterization of a new chiral phosphinothiol ligand and its palladium(II) complexes

Article abstract of DOI:10.1016/S0957-4166(02)00143-X

The chiral ligand (1-diphenylphosphino-3-benzyloxy)propane-2-thiol 3 has been prepared both in racemic and enantiomerically enriched (92% e.e.) form. Addition of 2 equiv. of ligand 3 to a solution of [Pd(PPh₃)₄] gave the diastereoisomeric bischelate complexes [Pd(phosphinothiolato)₂] 4 which exhibit a cis-trans equilibrium in solution. Formation of the diastereoisomeric complexes 4 allows the determination of the enantiomeric purity of ligand 3 by ³¹P NMR spectroscopy. Addition of 1 equiv. of ligand 3 to a solution of [PdCl₂(PPh₃)₂] gave the enantiomeric complexes [PdCl(phosphinothiolate)(PPh₃)] 5, which can be converted to the bischelate complexes 4 by addition of a second equivalent of ligand 3. This process allows the selective preparation of the two diastereoisomeric forms of complex 4.

Full text of DOI:10.1016/S0957-4166(02)00143-X

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 569–577
Synthesis and characterization of a new chiral phosphinothiol
ligand and its palladium(II) complexes
a
a
a,
b,
c
´
´
Nuria Brugat, Josep Duran, Alfonso Polo, * Julio Real, * Angel Alvarez-Larena and
J. Francesc Piniellac
aDepartament de Qu´ımica, Universitat de Girona, Campus de Montilivi s/n, 10071 Girona, Spain
bDepartament de Qu´ımica, Universitat Auto`noma de Barcelona, 08193 Bellaterra, Spain
cServei de Difraccio´ de Raigs-X and Unitat de Cristal.lografia i Mineralogia, Universitat Auto`noma de Barcelona,
08193 Bellaterra, Spain
Received 4 February 2002; accepted 15 March 2002
Abstract—The chiral ligand (1-diphenylphosphino-3-benzyloxy)propane-2-thiol 3 has been prepared both in racemic and enan-
tiomerically enriched (92% e.e.) form. Addition of 2 equiv. of ligand 3 to a solution of [Pd(PPh3)4] gave the diastereoisomeric
bischelate complexes [Pd(phosphinothiolato)2] 4 which exhibit a cis–trans equilibrium in solution. Formation of the diastereoiso-
meric complexes 4 allows the determination of the enantiomeric purity of ligand 3 by 31P NMR spectroscopy. Addition of 1 equiv.
of ligand 3 to a solution of [PdCl2(PPh3)2] gave the enantiomeric complexes [PdCl(phosphinothiolate)(PPh3)] 5, which can be
converted to the bischelate complexes 4 by addition of a second equivalent of ligand 3. This process allows the selective
preparation of the two diastereoisomeric forms of complex 4. © 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
electron pairs on sulfur. Moreover, the thiolate group
has only one substituent, the chain that connects it to
the phosphino group. Conversely, phosphorous is neu-
tral and once bound to the metal it does not support
any non-bonding electron pairs, acting as a classical
p-acceptor ligand. Chirality in phosphinothiolate lig-
ands can be introduced in different ways. It can be
achieved by means of the addition of a substituent in
the chelate chain, as in the case of 1-methyl-2-
(diphenylphosphino)ethane-1-thiol,7 or by the use of a
phosphino group with different substituents, as in the
case of 2-(phenylmethylphosphino)ethane-1-thiol.8 But
in both cases these ligands were obtained as racemic
mixtures. And only the latter phosphinothiolate ligand
was used to prepare a metal complex, the bischelate
bis{2-(phenylmethylphosphino)ethane-1-thiolato}palla-
dium(II), which proved to contain a mixture of all
structural possibilities in solution due to the racemic
nature of the ligand used.
Chelating chiral diphosphines are classical ligands
extensively used in metal-catalysed enantioselective pro-
cesses.1 Besides the asymmetry introduced by the
chelate ring, many of these diphosphines have two
donor atoms with similar electronic and steric proper-
ties (e.g. DIOP,2 BINAP3). In order to decrease the
symmetry of the bidentate ligand, diphosphines with
different substituents at each phosphorus have been
synthesized (e.g. DIPAMP4), and some chemical
changes in the phosphorous group have been intro-
duced (e.g. BINAPHOS5). Marked differentiation
between the coordinating groups is achieved with a
change in the chemical nature of one of the donor
atoms, as in the case of phosphinooxazolines6 where a
phosphorous donor atom is replaced by nitrogen, a
harder first period atom.
Phosphinothiolates are asymmetric chelating ligands
where one of the donor atoms, sulfur, supports a
formal negative charge and, once bound to the metal,
can act as a p-donor owing to the two non-bonding
As part of a project on the use of phosphinothiolate
complexes of the Group 10 metals as homogenous
catalysts,9,10 we have synthesized a new class of palladi-
um(II) complexes using (1-diphenylphosphino-3-benzyl-
oxy)propane-2-thiol 3, both in racemic and enantio-
merically enriched form.
* Corresponding authors. Fax: +34 (9)72418150 (A.P.); fax: +34
(9)35813101 (J.R.); e-mail: alfons.polo@udg.es; juli.real@uab.es
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00143-X

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N. Brugat et al. / Tetrahedron: Asymmetry 13 (2002) 569–577
glycidyl ether as starting materials. Thiiranes may be
2. Synthesis of chiral phosphinothiol ligands
stereoselectively synthesized from the corresponding
oxiranes using different agents: phosphine sulfides,11
benzothiazole-2-thiones12 and thiourea.13 For all these
methods a mechanism involving two Walden inversions,
one for each oxirane carbon has been proposed, indi-
cating that for terminal chiral oxiranes, as in our case,
the stereochemistry of the resulting episulfide is oppo-
site to that of the starting material. Reaction of thiirane
2 with potassium diphenylphosphide in THF at 0°C
was found to be a regioselective process where only the
SN2 product was observed. The resulting phosphino-
thiol ligand has the opposite stereochemistry to the
starting oxirane, but the same absolute configuration (S
or R) due to a change in the C.I.P. substituent order of
precedence.14
The ligand (1-diphenylphosphino-3-benzyloxy)propane-
2-thiol 3 was prepared in a three-step synthesis accord-
ing to Scheme 1. In the first step, reaction of benzyl
alcohol and epichlorohydrin gave the benzyl glycidyl
ether 1 in good yield (85%) upon treatment with
aqueous potassium hydroxide in the presence of a small
amount of tetrabutylammonium bromide as phase
transfer catalyst. It has been determined that the phase
transfer agent is an important additive for this reaction
to proceed to completion. Compound 1 was converted
into the corresponding episulfide, the benzyl thiogly-
cidyl ether 2, using thiourea as the sulfur exchange
agent (58%). Treatment of compound 2 with 1 equiv. of
potassium diphenylphosphide in THF at 0°C gave (1-
diphenylphosphino-3-benzyloxy)propane-2-thiol 3, in a
75% yield.
3. Synthesis of bis(phosphinothiolate)palladium(II)
complexes
Compounds 1–3 were characterized by NMR spec-
troscopy. In the 1H NMR spectrum, compound 3
shows the resonance of the thiol proton as a doublet
from coupling to the hydrogen on the stereogenic car-
bon atom. The proton attached to the stereogenic
center appears as a multiplet due coupling with six
different nuclei (2CH2, SH, 31P). The methylenic pro-
tons near the phosphine group are diastereotopic and
show a 2J coupling constant with the phosphorous
3.1. Use of the racemic ligand
The complex bis{1-diphenylphosphino-3-benzyloxy)-
propane-2-thiolato}palladium(II) 4 can be obtained in
good yield (86%) via oxidative addition of 2 equiv. of
racemic ligand 3 to a solution of [Pd(PPh3)4] at room
temperature (Scheme 2).9 Bischelate complex 4 exists as
a mixture of the cis and trans isomers in solution, which
are present in different amounts owing to their relative
stabilities. Phosphorous NMR spectroscopy proved to
be the best tool to analyze the composition of the
isomeric mixtures, because cis–trans interconversion
equilibria are kinetically slow.
1
atom, as it can be seen in the H{31P} NMR spectrum.
In the 13C{1H} NMR spectrum all carbon signals
appear as doublets by coupling with the phosphorous
atom, with the exception of the methylenic carbon of
the benzyl group. In the 31P{1H} NMR spectrum,
compound 3 shows a single resonance at −20.53 ppm.
Enantiomerically enriched forms of compound 3 can be
obtained by the same synthetic process using commer-
cial benzyl (R)-(−)-glycidyl ether and benzyl (S)-(+)-
The isomeric trans/cis-4 complexes were characterized
by NMR spectroscopy. Freshly prepared CD2Cl2 solu-
tions of 4 show four resonances at 55.54, 54.45, 50.56
and 47.55 ppm in a 95:95:5:5 intensity ratio (Fig. 1a) in
the 31P{1H} spectrum. The two larger phosphorous
signals and the smaller ones show an equilibration
process at room temperature leading to an intensity
ratio of 66:66:34:34 (Fig. 1b) after 24 h. This dynamic
process is inverted by crystallization of the product and
it can also be frozen by cooling the solution to −22°C.
These observations are attributed to the chemical equi-
librium between trans and cis geometries of the com-
plexes and has been described for other
bis(phosphinothiolato) complexes of palladium(II).8,15
This equilibrium exists only in solution, in the solid
state complex 4 adopts a trans geometry.9,16 The trans
geometry of the two major diastereomers is also con-
Scheme 1. Synthesis of (1-diphenylphosphino-3-benzyloxy)-
propane-2-thiol 3. (a) NaOH/H2O, n-Bu4NBr. (b) SC(NH2)2/
EtOH/H2O. (c) (i) KPPh2, (ii) NH4Cl.
Scheme 2. Synthesis of chiral bis(phosphinothiolato)palladium(II) complexes 4.

N. Brugat et al. / Tetrahedron: Asymmetry 13 (2002) 569–577
571
In keeping with the conformational analysis of com-
pounds trans-4 and cis-4 (Scheme 3), the preferred
conformation for the chiral chelate ring depends on the
configuration of the stereogenic carbon of the ligand
chain. In this way, the ligand with R configuration
adopts the u conformation, which places the substituent
of the chelate ring in equatorial position. For the same
reasons, the ligand with S configuration adopts the l
conformation. As a result of these conformational pref-
erences, complexes with the same geometry carrying
two ligands with the same configuration, trans-(R,R)-4
and trans-(S,S)-4 or cis-(R,R)-4 and cis-(S,S)-4 are
enantiomers producing a single 31P{1H} NMR signal
even at low temperatures. Furthermore, these com-
plexes are diastereomers of the corresponding com-
plexes carrying one ligand in each configuration,
trans-(R,S)-4 and cis-(R,S)-4. This conformational
analysis allows us to assign the two major 31P{1H}
signals, one to the trans-(R,S)-4 complex and the other
to a mixture of trans-(R,R)-4 and trans-(S,S)-4 com-
plexes. It is also possible to assign the two minor
31P{1H} signals, one to the cis-(R,S)-4 complex and the
other to a mixture of cis-(R,R)-4 and cis-(S,S)-4 com-
plexes. The assignment of each 31P{1H} signal to their
corresponding complex will be possible after the prepa-
ration of complexes 4 using enantiomerically enriched
ligands.
Figure 1. 31P{1H} NMR spectra of 4 obtained using racemic
ligand 3. (a) Freshly prepared CD2Cl2 solution. (b) After 24 h
in solution.
firmed by the 13C{1H} spectrum, where the absorptions
of three aliphatic carbons of the ligand chain appear as
triplets owing to coupling with the 2 equiv. phospho-
rous centers mutually in trans positions.9,16 Only the
secondary carbons corresponding to the benzyl groups
appear as singlets.
3.2. Use of enantiomerically enriched ligands
Addition of 2 equiv. of enantiomerically enriched lig-
and 3 to a solution of complex [Pd(PPh3)4] at room
temperature gave a product 4 showing the same NMR
spectra independently of the configuration of the ligand
used. Freshly prepared CD2Cl2 solutions of the product
show three resonances at 55.54, 54.45 and 47.55 ppm in
Figure 2. 31P{1H} NMR spectra of 4 obtained using enan-
tiomerically enriched ligand 3. (a) Freshly prepared CD2Cl2
solution. (b) After 24 h in solution.
Scheme 3. Conformational analysis for complexes 4.

572
N. Brugat et al. / Tetrahedron: Asymmetry 13 (2002) 569–577
a 4:91:5 intensity ratio in the 31P{1H} spectrum (Fig.
2a). The main phosphorous signal and the small reso-
nance at 47.55 ppm show the equilibration process
already observed using the racemic ligand, leading to
an intensity ratio of 66:34, respectively, after 24 h at
room temperature (Fig. 2b).
sponding signals for trans-(R,S)-4 and for the enan-
tiomers trans-(R,R)-4 and trans-(S,S)-4.
4. Synthesis of chiral {chloro(phosphinothiolato)-
triphenylphosphine}palladium(II) complexes
Addition of 1 equiv. of racemic ligand 3 to a solution of
[PdCl2(PPh3)2] at room temperature in the absence of
base produced the corresponding chloro complexes
[PdCl(phosphinothiolate)(PPh3)] 5 in good yield (70%)
(Scheme 4).9 The complexes were isolated as orange
solids and were characterized by NMR spectroscopy. In
solution, complex 5 exhibits an equilibrium between the
trans and cis geometries, as can be seen in the 31P{1H}
NMR spectrum (Fig. 3).
These observations lead to the assignment of the signals
at 54.45 and 47.55 ppm to a mixture of trans-(R,R)-4
and trans-(S,S)-4 enantiomeric complexes and to a
mixture of cis-(R,R)-4 and cis-(S,S)-4 enantiomeric
complexes, respectively. The signal at 55.54 ppm was
then assigned to the meso complex trans-(R,S)-4, which
also shows an equilibration process with a new signal
appearing at 50.56 ppm after 24 h in solution at room
temperature. This new absorption is then assigned to
the meso complex cis-(R,S)-4. An important observa-
tion is that the intensity ratio between the major
31P{1H} signal at 54.45 ppm, and the minor absorption
due to trans-(R,S)-4 at 55.54 ppm, remains constant
(96:4) after 48 h at room temperature. This suggests
that racemization of the ligand does not occur. Under
the right conditions the integration of the NMR signals
obtained provides an excellent method to calculate the
enantiomeric purity (92% e.e.) of the phosphinothiolate
ligands coordinated to palladium.17 The comparison of
the 1H and 13C{1H} NMR spectra of complexes 4
carrying either racemic ligands or enantiomerically
enriched ligands allows the assignment of the corre-
This equilibrium is strongly displaced toward the trans
form (95%). The use of enantiomerically enriched lig-
ands 3 in the synthesis of complexes 5 gave a product
with identical NMR spectra, independently of the
configuration of the ligand used, pointing to the simple
existence of a pair of enantiomers. In keeping with the
conformational analysis of complexes 5 (Scheme 5),
much as for bischelate complexes 4, the preferred con-
formation of the chelate ring depends on the configura-
tion of the stereogenic carbon of the ligand. The chelate
ring with R configuration adopts the u conformation,
which places the substituent in an equatorial disposi-
tion. For the same reasons, the chelate ring with the
Scheme 4. Synthesis of chiral {chloro(phosphinothiolato)triphenylphosphine}palladium(II) complexes 5.
Figure 3. 31P{1H} NMR spectra of 5 obtained using both enantiomerically enriched or racemic ligand 3.

N. Brugat et al. / Tetrahedron: Asymmetry 13 (2002) 569–577
573
6). In a faster reaction, the reverse process allowed the
preparation of bischelate complexes 4 by the addition
of 1 equiv. of ligand 3 to a solution of the chloro
complexes 5 at room temperature.9
The synthesis of bischelate complexes from chloro com-
plexes provides a method to prepare the meso complex
trans-(R,S)-4 by addition of 1 equiv. of ligand 3 in the
(R)-enantiomerically enriched form to a solution of
complex trans-(S)-5, as depicted in Scheme 7. Freshly
prepared CD2Cl2 solutions of the recovered product
show the signal assigned to complex trans-(R,S)-4 as
the major one in the 31P{1H} spectrum (Fig. 4a). Com-
plex trans-(R,S)-4 equilibrates rapidly with the trans-
Scheme 5. Conformational analysis for complexes 5.
(S)-configuration adopts a l conformation. As a result
of these conformational preferences, complexes with the
same geometry and different configuration of the
stereogenic carbon of the chelate ring, trans-(R)-5 and
trans-(S)-5 or cis-(R)-5 and cis-(S)-5, are enantiomers
producing the same NMR signals. In this case, the
introduction of a single stereogenic carbon into the
complex
does
not
produce
diastereoisomeric
differentiation.
5. Interconversion between bischelate and chloro
complexes
The bischelate complexes 4 could be converted into
chloro complexes 5 in good yield (>90%), by a simple,
albeit slow metathesis reaction with an equivalent of
[PdCl2(PPh3)2] in refluxing toluene over 24 h (Scheme
Figure 4. 31P{1H} NMR spectra of 4 obtained by addition of
1 equiv. of ligand (R)-3 to complex trans-(S)-5. (a) Freshly
prepared CD2Cl2 solution. (b) After 2 h in solution.
Scheme 6. Interconversion between bischelate 4 and chloro 5 complexes.
Scheme 7. Selective formation of complex trans-(R,S)-4.

574
N. Brugat et al. / Tetrahedron: Asymmetry 13 (2002) 569–577
(R,R)-4 and trans-(S,S)-4 complexes and after 2 h the
two signals have the same intensity (Fig. 4b), pointing
to the tendency of the phosphinothiolate ligands in this
system towards the exchange process.
respectively.15 The Pd–S distance in cis-P,S-
[PdCl(PPh2CH2CH2S)(PPh3)] is shorter (2.270(2) A)
,
owing to the lower influence of chlorine, but the chelate
9
,
Pd–P distance is comparable, 2.288(2) A. Shorter Pd–S
,
,
(2.253(2) A) and Pd–P (2.254(2) A) distances are
observed in the nitrogen donor containing cysteine
complex cis-P,S-[PdCl(SCH2CH(CO2Et)NH2)(PPh3)].10
6. Crystal structure of trans-(S,S)-4
The planarity of the PdS2P2 group is slightly distorted,
owing most probably to packing forces in the solid
state. The chelate chain carbons are displaced from the
plane, adopting a l conformation that places the sub-
stituents in equatorial positions (Fig. 5).
The X-ray analysis study was carried out on the com-
pound after recrystallization from CH2Cl2/hexane
(Table 1). Selected distances and angles are listed in
Table 2. The structure of trans-(S,S)-4 (Fig. 5)18,19
reveals a mononuclear square planar trans palladium
complex with Pd–S and Pd–P distances of 2.313(2) and
,
2.281(2) A, which are consistent with their respective
7. Experimental
trans influences. These values can be compared to those
,
in trans-[Pd(PPh2C6H4-2-S)2], 2.308(2) and 2.291(1) A,
All complexes were synthesized using standard Schlenk
techniques under a nitrogen atmosphere. Solvents were
dried by standard methods and distilled and deoxy-
genated before use. Complexes Pd(PPh3)4, PdCl2(PPh3)2
and PdCl2(PhCN)2 were prepared as previously
reported.20–22 C, H and S analyses were carried out
using a Carlo–Erba microanalyser. Infrared spectra
(range 4000–400 cm−1) were recorded on a Nicolet 205
spectrophotometer. Deuterated solvents for NMR mea-
surements were dried over molecular sieves. Proton
NMR spectra were recorded at 300 and 200 MHz on a
Varian Gemini-300 and Bruker DPX-200 spectrome-
ters, respectively. Peak positions are relative to tetra-
methylsilane as internal reference. 31P{1H} NMR
spectra were recorded on the same instruments operat-
ing at 121.4 and 81.0 MHz, respectively. Chemical
shifts are relative to external 85% H3PO4, with
downfield values reported as positive. 13C{1H} NMR
spectra were recorded on the same instruments operat-
ing at 75.4 and 50.3 MHz, respectively. Chemical shifts
are relative to tetramethylsilane as internal reference.
Gas chromatography analyses were performed on a
Shimatzu GC-17A in a TRB-2 (5% diphenylsilicone–
95% dimethylsilicone) column (30 m×0.25 ¥). Flash
chromatography was performed on silica gel 60 A CC.
Solvents for chromatography were distilled at atmo-
spheric pressure prior to use. Microdistillation proce-
dures were performed on a Buchi GK-R-51. The X-ray
analysis study was carried out on a Enraf–Nonius
CAD-4 diffractometer at room temperature, graphite
monochromatized Mo Ka radiation and the ꢀ/2q scan
mode. Cell parameters were determined by least-square
refinement on diffractometer parameters for 25 auto-
matically centered reflections. Lp and empirical absorp-
tions corrections were applied.23 The structures were
solved by direct methods using the program SHELXS-
8624 and refined on F2 for all reflections using
SHELXL-97.25 The non-hydrogen atoms were refined
with anisotropic displacement parameters. Hydrogen
atoms were placed at their calculated positions with
isotropic temperature factors equal to 1.2 times the Ueq
values of the corresponding carbons. Benzenic rings
were refined as rigid bodies. Crystallographic data and
structure refinement parameters are presented in Table
1, and selected distances and angles in Table 2.
,
and cis-[Pd(PPh2C6H4-2-S)2], 2.391(1) and 2.282(1) A,
Table 1. Crystallographic data for complex trans-(S,S)-4
Empirical formula
FW
C44H44O2P2PdS2
837.25
Temperature (K)
293(2)
,
Wavelength (A)
Crystal system
Space group
0.71069
Monoclinic
P21/n
,
a (A)
10.116(1)
9.410(7)
21.331(6)
90
99.27(2)
90
2004(2)
2
1.388
,
b (A)
,
c (A)
h (°)
i (°)
k (°)
3
,
Volume (A )
Z
Calculated density (g cm−1
)
Absorption coefficient (mm−1
Unique data/parameters
R(Fo) [I\2|(I)]a
)
6.83
3757/388
0.0467
Rw(Fo2) (all data)b
0.1032
Flack parameter
−0.04(4)
a R(Fo)=SꢀFoꢀ−ꢀFcꢁ/SꢀFoꢀ.
b Rw(Fo2)=[Sw(Fo2−Fc2)2/S(Fo2)2]1/2
.
,
Table 2. Selected bond distances (A) and angles (°) for
complex trans-(S,S)-4
Distances
PdꢀP1
PdꢀP2
PdꢀS1
PdꢀS2
S1ꢀC2
C1ꢀC2
2.280(2)
2.282(2)
2.307(2)
2.319(2)
1.847(8)
1.504(11)
C1ꢀP1
C2ꢀC31
S2ꢀC4
C3ꢀC4
C3ꢀP2
C4ꢀC61
1.851(7)
1.533(13)
1.824(8)
1.522(10)
1.821(7)
1.513(9)
Angles
P1ꢀPdꢀP2
P1ꢀPdꢀS1
P2ꢀPdꢀS1
P1ꢀPdꢀS2
P2ꢀPdꢀS2
S1ꢀPdꢀS2
C2ꢀS1ꢀPd
C2ꢀC1ꢀP1
178.70(6)
C1ꢀC2ꢀC31
C1ꢀC2ꢀS1
C31ꢀC2ꢀS1
C4ꢀS2ꢀPd
C4ꢀC3ꢀP2
C61ꢀC4ꢀC3
C61ꢀC4ꢀS2
C3ꢀC4ꢀS2
113.5(7)
86.96(7)
94.15(7)
92.48(7)
86.44(7)
177.4(1)
107.6(3)
112.5(6)
113.1(6)
108.9(6)
105.3(2)
108.4(5)
111.7(7)
107.0(5)
111.6(6)

N. Brugat et al. / Tetrahedron: Asymmetry 13 (2002) 569–577
575
Figure 5. ORTEP plots of trans-(S,S)-4.
Crystallographic data (excluding structure factors) for the
structure in this paper has been deposited with the
Cambridge Crystallographic Data Centre as supplemen-
tary publication number CCDC 167715. Copies of the
data can be obtained, free of charge, on application to
CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK [fax:
+44(0)-1223-336033 or e-mail: deposit@ccdc.cam.ac.uk].
butylammonium bromide (1.5 g, 4.7 mmol) was vigor-
ously stirred at room temperature and placed in an ice
bath. Benzyl alcohol (10 mL, 96.0 mmol) was gradually
added over 10 min, the temperature did not exceed
25°C. The progress of the reaction was monitored by
GLC; after 12 h, the reaction was complete and the
reaction mixture was poured on ice/water (60 mL). The
aqueous phase was extracted with diethyl ether (3×40
mL). The organic phase was washed with brine to
neutrality, dried with magnesium sulfate, filtered, evap-
orated to dryness, and distilled at atmospheric pressure
(205–210°C) to yield benzyl glycidyl ether 1 of purity
7.1. Preparation of (1-diphenylphosphino-3-benzyloxy)-
propane-2-thiol 3
Step 1. A mixture of 50% w/w aqueous potassium
hydroxide (60 mL), epichlorohydrin (40 mL) and tetra-
1
>98% by GLC (13.4 g, 85%). H NMR (CDCl3 sol.): l

576
N. Brugat et al. / Tetrahedron: Asymmetry 13 (2002) 569–577
2
3
7.2. General procedure for preparation of bis-
{1-diphenylphosphino-3-benzyloxy)propane-2-thio-
lato}palladium(II) complexes 4
2.62 (dd, 1H, J=5.0 Hz, J=2.7 Hz); 2.80 (dd, 1H,
2J=5.0 Hz, J=4.2 Hz); 3.19 (m, 1H); 3.44 (dd, 1H,
3
3
2
2J=11.4 Hz, J=5.8 Hz); 3.77 (dd 1H, J=11.4 Hz,
3J=3.0 Hz); 4.59 (m, 2H), 7.0–8.0 (m, 5H). 13C{1H}
NMR (CDCl3 sol.): l 44.25 (s, CH2); 50.82 (s, CH);
70.76 (s, CH2); 73.28 (s, CH2); 125.0–130.0 (C arom.).
(1-Diphenylphosphino-3-benzyloxy)propane-2-thiol
3
(262.0 mg, 0.57 mmol) was added to a solution of
complex [Pd(PPh3)4] (300.0 mg, 0.27 mmol) in anhy-
drous dichloromethane (10 mL) under a nitrogen
atmosphere to produce an intense yellow solution. The
reaction mixture was stirred at room temperature.
After 1 h, the volume was reduced to 5 mL and the
product was crystallized by the addition of hexane to
afford the complex as orange crystals (187 mg, 86%).
Anal. found: C, 63.4; H, 5.45; S, 7.4%. C44H44P2PdS2
calcd: C, 63.1; H, 5.29; S, 7.7. Complex trans-(R,R)-4
or trans-(S,S)-4 1H NMR (CD2Cl2 sol.): l 2.76 (m,
1H, H1); 3.05 (m, 1H, H1%); 3.21 (m, 2H, H3); 3.61 (m,
1H, H2); 4.30 (m, 2H, H4); 7.0–8.0 (m, 15H, Har.).
13C{1H} NMR (CD2Cl2 sol.): l 41.39 (t, CH, C2,
JC P=10.3 Hz); 42.09 (t, CH2, C1, JC P=17.4 Hz);
Step 2. Thiourea (9.3 g, 122.4 mmol), benzyl glycidyl
ether 1 (13.4 g, 81.6 mmol), water (8.1 mL) and etha-
nol (40.8 mL) were introduced in a reactor and vigor-
ously stirred at room temperature. The progress of the
reaction was monitored by GLC; after 12 h, the reac-
tion was complete and water (20 mL) was added to
the reaction mixture. The aqueous phase was extracted
with diethyl ether (3×20 mL). The organic phase was
washed with water (20 mL), dried with magnesium
sulfate, filtered, evaporated to dryness, and distilled
under vacuum (135–145°C, 0.1 Torr) benzyl thiogly-
cidyl ether 2 of purity >98% by GLC was obtained
1
(8.4 g, 58%). H NMR (CDCl3 sol.): l 2.36 (dd, 1H,
–
–
2J=1.2 Hz, J=5.5 Hz); 2.52 (dpst, 1H, J=1.2 Hz,
3
2
73.10 (s, CH2, C4); 76.59 (t, CH2, C3, JC P=8.7 Hz);
–
3J=6.0 Hz, 4J=0.8 Hz); 3.1 (m, 1H); 3.49 (dd 1H,
125.0–135.0 (C arom.). 31P{1H} NMR (CD2Cl2 sol): l
54.45 (s). Complex cis-(R,R)-4 or cis-(S,S)-4 31P{1H}
NMR (CD2Cl2 sol.): l 47.55 (s). Complex trans-(R,S)-
2J=10.6 Hz, J=6.7 Hz); 3.69 (ddd 1H, J=10.6 Hz,
3J=5.7 Hz, 4J=0.8 Hz); 4.59 (m, 2H), 7.0–8.0 (m,
5H). 13C{1H} NMR (CDCl3 sol.): l 23.79 (s, CH2);
32.16 (s, CH); 73.12 (s, CH2); 74.67 (s, CH2); 125.0–
130.0 (C arom.).
3
2
1
4 H NMR (CD2Cl2 sol.): l 2.84 (m, 1H, H1); 3.03
(m, 1H, H1%); 3.21 (m, 2H, H3); 3.63 (m, 1H, H2); 4.28
(m, 2H, H4); 7.0–8.0 (m, 15H, Har.). 13C{1H} NMR
(CD2Cl2 sol.): l 41.60 (t, CH, C2, JC P=10.6 Hz);
–
Step 3. Benzyl thioglycidyl ether 2 (1.1 g, 6.11 mmol)
was slowly added to an ice-cold solution of potassium
diphenylphosphide (0.5 M in tetrahydrofuran, 12.2
mL, 6.1 mmol), with stirring under a nitrogen atmo-
sphere. The reaction mixture was then vigorously
stirred at room temperature. After 30 min, deoxy-
genated methanol (4 mL), deoxygenated saturated
ammonium chloride aqueous solution (5 mL), and
deoxygenated water (10 mL) were consecutively added
to the reaction mixture. The aqueous phase was
extracted with diethyl ether (3×15 mL). The organic
phase was washed with water (15 mL), dried with
magnesium sulfate, filtered and evaporated to dryness.
Purification of the crude product by flash chromatog-
raphy (hexane/ethyl acetate: 8/2) afforded (1-
41.95 (t, CH2, C1, JC P=17.0); 73.00 (s, CH2, C4);
–
76.52 (t, CH2, C3, JC P=8.6 Hz); 125.0–135.0 (C
–
arom.). 31P{1H} NMR (CD2Cl2 sol.): l 55.54 (s).
Complex cis-(R,S)-4 31P{1H} NMR (CD2Cl2 sol.): l
50.56 (s).
7.3. General procedure for the preparation of chloro-
{(1-diphenylphosphino-3-benzyloxy)propane-2-thio-
lato)triphenylphosphine}palladium(II) complexes 5
(1-Diphenylphosphino-3-benzyloxy)propane-2-thiol
3
(80.0 mg, 0.21 mmol) was added to a solution of
complex [PdCl2(PPh3)2] (150.0 mg, 0.21 mmol) in
anhydrous dichloromethane (10 mL) under a nitrogen
atmosphere to produce an orange solution. The reac-
tion mixture was stirred at room temperature. After 1
h, the volume was reduced to 3 mL and the product
was crystallized by addition of hexane and cooling the
mixture to −20°C for 12 h. Complex 5 was obtained
as orange crystals (117 mg, 70%). Anal. found: C,
62.3; H, 5.13; S, 4.1%. C40H37ClP2PdS calcd: C, 62.4;
diphenylphosphino-3-benzyloxy)propane-2-thiol
3 of
purity >98% by NMR (1.67 g, 75%). 1H NMR
3
(CDCl3 sol.): l 2.19 (d, SH, J=6.3 Hz); 2.33 (ddd,
2
3
2
1H, H1, J=14.0 Hz, J=8.3 Hz, JH–P<0.5 Hz); 2.64
(ddd, 1H, H1%, 2J=14.0 Hz, 3J=6.4 Hz, 2JH–P=1.2
2
Hz); 3.11 (m, 1H, H2); 3.57 (dd, 1H, H3, J=9.5 Hz,
3J=6.0 Hz); 3.65 (dd, 1H, H3%, 2J=9.5 Hz, 3J=5.8
Hz); 4.49 (s, 2H, H4), 7.0–8.0 (m, 15H, Har.). 13C{1H}
1
H, 4.84; S, 4.4. Complex trans-(R)-5 or trans-(S)-5 H
2
NMR (CD2Cl2 sol.): l 2.94 (m, 2H, H1); 3.17 (m, 2H,
H3); 3.48 (m, 1H, H2); 4.23 (m, 2H, H4); 7.0–8.0 (m,
30H, Har.). 13{1H} NMR (CD2Cl2 sol.): l 42.44 (d,
CH2, C1, JC P=34.4 Hz); 43.04 (d, CH, C2, JC P=10.3
NMR (CDCl3 sol.): l 34.70 (d, CH, C2, JC–P=11.3
Hz); 37.48 (d, CH2, C1, 1JC P=16.4 Hz); 72.96 (s,
–
CH2, C3); 75.59 (d, CH2, C4, 3JC P=8.4 Hz); 125.0–
–
135.0 (C arom.). 31P{1H} NMR (CDCl3 sol.): l −20.53
–
–
Hz); 73.07 (s, CH2, C4); 75.50 (d, CH2, C3, JC P=18.2
–
(s).
Hz); 125.0–135.0 (C arom.). 31P{1H} NMR (CD2Cl2
sol.): l 23.45 (d, PPh3, 2JP–P=463.6 Hz); 57.56 (d,
Enantiomerically enriched ligands (R)-3 and (S)-3
were obtained through synthetic steps 2 and 3, starting
from commercial benzyl (R)-(−)-glycidyl ether and
benzyl (S)-(+)-glycidyl ether, respectively.
2
–PPh2, JP–P=463.6 Hz). Complex cis-(R)-5 or cis-(S)-
2
5
31P{1H} NMR (CD2Cl2 sol.): l 23.64 (d, PPh3, JP–
2
P=13.4 Hz); 63.60 (d, –PPh2, JP–P=13.4 Hz).

N. Brugat et al. / Tetrahedron: Asymmetry 13 (2002) 569–577
577
7.4. Interconversion between chloro and bischelate
complexes
4. Knowles, W. S.; Sabacky, M. J.; Vineyard, B. D. Adv.
Chem. Ser. 1974, 132, 274.
5. Sakai, N.; Mano, S.; Nozaki, K.; Takaya, H. J. Am.
Chem. Soc. 1993, 115, 7033.
6. Koch, G.; Lloyd-Jones, G. C.; Loiseleur, O.; Pfaltz, A.;
Pre´tot, R.; Schaffner, S.; Schnider, P.; von Matt, P. Recl.
Trav. Chim. Pays-Bas 1995, 114, 206.
7. Wieber, M.; Clarius, T. Z. Anorg. Allg. Chem. 1995, 621,
1288.
7.4.1. General procedure for preparation of bischelates
from chloro complexes. (1-Diphenylphosphino-3-benzyl-
oxy)propane-2-thiol 3 (48.0 mg, 0.13 mmol) was added
to a solution of complex 5 (100.0 mg, 0.13 mmol) in
anhydrous dichloromethane (8 mL) under a nitrogen
atmosphere to produce an orange solution. The reac-
tion mixture was stirred at room temperature for 2 h.
The volume of the mixture was reduced to 5 mL and
the product was crystallized by addition of hexane.
Complex 4 was obtained as orange crystals (87 mg,
80%).
8. Leung, P. H.; Martin, J. W. L.; Wild, S. B. Inorg. Chem.
1986, 25, 3396.
´
9. Brugat, N.; Polo, A.; Alvarez-Larena, A.; Piniella, J. F.;
Real, J. Inorg. Chem. 1999, 38, 4829.
10. Real, J.; Page`s, M.; Polo, A.; Piniella, J. F.; Alvarez-
´
Larena, A. Chem. Commun. 1999, 277.
11. Chan, T. H.; Finkenbine, J. R. J. Am. Chem. Soc. 1972,
94, 2880.
12. Calo`, V.; Lopez, L.; Marchese, L.; Pesce, G. J. Chem.
Soc., Chem. Commun. 1975, 621.
7.4.2. General procedure for the preparation of chloro
complexes from bischelates. A mixture of complex
[PdCl2(PPh3)2] (125.7 mg, 0.18 mmol) and bis-
{(1-diphenylphosphino-3-benzyloxy)propane-2-thiolato}-
palladium(II) complex 4 (150 mg, 0.18 mmol) in tolu-
ene (30 mL) was heated under reflux under a nitrogen
atmosphere. After 24 h, the volume of the mixture was
reduced to 5 mL and the product was crystallized by
cooling to −20°C for 12 h. The crude product was
filtered and washed with hexane and diethyl ether.
Complex 5 was obtained as orange crystals (256 mg,
93%).
13. Bouda, H.; Borredon, M. E.; Delmas, M.; Gaset, A.
Synth. Commun. 1989, 19, 491.
14. Prelog, V.; Helchem, G. Angew. Chem., Int. Ed. Engl.
1982, 21, 567.
´
15. Real, J.; Prat, E.; Polo, A.; Alvarez-Larena, A.; Piniella,
J. F. Inorg. Chem. Commun. 2000, 3, 221.
16. Kita, M.; Yamamoto, T.; Kashiwaba, K.; Fujita, I. Bull.
Chem. Soc. Jpn. 1992, 65, 2272.
17. Glowacki, Z.; Topolski, M.; Matczat-Jon, E.; Hoffmann,
M. Magn. Res. Chem. 1989, 27, 922.
Acknowledgements
18. Burnet, M. N.; Johnson, C. J. ORTEP-III: Oak Ridge
Thermal Ellipsoid Plot Program for Crystal Structure
Illustrations; Oak Ridge National Laboratory Report
ORNL-6895; Oak Ridge National Laboratory: Oak
Ridge, TN, 1996.
19. Farrugia, L. J. J. Appl. Crystallogr. 1997, 565.
20. Coulson, D. R. Inorg. Synth. 1972, 13, 121.
21. Colquhoun, H. M.; Holton, J.; Thompson, D. J.; Twigg,
M. V. New Pathways for Organic Synthesis; Plenum
Press, 1984.
This work was financially supported by the CICYT-
DGR, project QFN95-4725-C03; and the DGESIC,
project PB98-0913-C02. Johnson Mathey is thanked for
the loan of palladium.
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