Platinum-assisted preparation of PS ligands containing chiral centres; X-ray crystal structure of a dithiophosphinite platinum complex

Article abstract of DOI:10.1016/j.ica.2004.12.027

The design and synthesis of some ligands containing P(III) bonded to sulfur (thiophosphinites) and chiral centres is described in this paper. Their complexes with platinum (II), [PtCl₂L], (L = bidentate dithiophosphinite) have been prepared and characterised and it has been shown that in many cases, the coordination to platinum protects these ligands from decomposition processes operated by moisture and oxygen. The first example of X-ray crystal structure of a platinum coordinated dithiophosphinite is described for complex cis-[PtCl₂L], [L = meso-2,3-bis(diphenylthiophosphinito) -dimethyl-succinate], 4a.

Full text of DOI:10.1016/j.ica.2004.12.027

Inorganica Chimica Acta 358 (2005) 2031–2039
www.elsevier.com/locate/ica
Platinum-assisted preparation of PS ligands containing chiral centres;
X-ray crystal structure of a dithiophosphinite platinum complex
*
Paola Bergamini , Valerio Bertolasi, Raffaele Giordani
`
Dipartimento di Chimica e Centro di Strutturistica Diffrattometrica dellÕUniversita di Ferrara, via L. Borsari 46, 44100 Ferrara, Italy
Received 19 November 2004; accepted 28 December 2004
Abstract
The design and synthesis of some ligands containing P(III) bonded to sulfur (thiophosphinites) and chiral centres is described in
this paper.
Their complexes with platinum (II), [PtCl2L], (L = bidentate dithiophosphinite) have been prepared and characterised and it has
been shown that in many cases, the coordination to platinum protects these ligands from decomposition processes operated by mois-
ture and oxygen. The first example of X-ray crystal structure of a platinum coordinated dithiophosphinite is described for complex
cis-[PtCl2L], [L = meso-2,3-bis(diphenylthiophosphinito)-dimethyl-succinate], 4a.
ꢀ 2005 Elsevier B.V. All rights reserved.
Keywords: Ligand design; P ligands; Platinum; Asymmetric catalyst
1. Introduction
On the contrary, to our knowledge, the use of thio-
phosphinites in catalysis has not been proposed so far.
This could be due to the general tendency to avoid sulfur
in catalysis for its well-known tendency to poison metal-
lic catalysts in heterogeneous catalysis [7]. The ground-
lessness of this attitude has been recently demonstrated
by the work of Evans et al. [8], who reported the prom-
ising results of sulfur containing ligands like aminophos-
phanes-thiols and aminophosphanes-thioethers in the
enantioselective rhodium-catalysed hydrogenation of
dehydroaminoacids and hydrosilylation of ketones (up
to 98% enantiomeric excess in both processes).
In 2001, a paper by Woollins and co-workers de-
scribed the preparation of a thiophosphinite-amino-
phosphane deriving from the natural occurring
aminoacid cystein. The authors did not mention the pos-
sibility of testing this ligand in asymmetric catalysis,
probably because of the instability they reported for
the palladium (II) complex [9].
The use of chiral diphosphanes has been extremely
successful in homogeneous metal catalysed asymmetric
processes, particularly double bond hydrogenation [1].
Nevertheless, because of several limitations like diffi-
culty in diphosphanes synthesis and the narrow range
of substrates they can work with, the search of new chi-
ral auxiliaries for catalysis is still a very lively topic.
In recent years, the activity of new families of P(III)
ligands containing P–X bonds (X = O or N), like
diphosphinites, aminophosphane-phosphinites (AMPP),
amino-phosphinites (AMP) and bis(amino)phosphanes
(BAMP), has been considered because of their synthetic
accessibility from widely available asymmetric molecules
deriving from the natural chiral pool. We [2,3] and oth-
ers [4–6] have described synthetic processes for the con-
struction of P(III) bonds with oxygen or nitrogen.
In this paper, we describe a group of asymmetric li-
gands containing PS bonds and we propose the coordi-
nation to platinum (II) as a way to stabilise them and to
*
Corresponding author. Tel.: +39 532 291129; fax: +39 532 240709.
E-mail address: bgp@unife.it (P. Bergamini).
0020-1693/$ - see front matter ꢀ 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.ica.2004.12.027

2032
P. Bergamini et al. / Inorganica Chimica Acta 358 (2005) 2031–2039
avoid decomposition processes induced by oxygen and
moisture.
the advantage of route 2 is an improvement of the yield
of 1a: 67% for route 2 versus 52% of route 1.
When treated with an excess of CNÀ as tetrabutylam-
monium salt in CDCl3, 1a releases ligand 1, as checked
comparing the 31P NMR with the above reported data
of the free ligand.
2. Results and discussion
2.1. Preparation of
derivatives
L
-cysteine methyl ester hydrochloride
Comparing the data of 1 and its Pt dichloro com-
plexes with the corresponding oxygenated analogues
SH
S
PPh2
PPh2
[PtCl2(1,5-COD)]
COD
2 PPh2Cl
*
*
+
NH3
N
H
MeOOC
MeOOC
3 Et3N
1
route 1
CN-
Ph2
P
S
Cl
Cl
Pt
*
P
N
MeOOC
Ph2
H
1a
ClPh2P
ClPh2P
Cl
Cl
Cl
Cl
3 Et3N
2 PPh2Cl
Pt
Pt
SH
*
+
MeOOC NH3
COD
route 2
Ligand 1 was generated in solution following the
preparation reported by Woollins and co-workers [9]
and it was then directly reacted with [PtCl2(1,5-COD)]
giving complex 1a which is, to our knowledge, the first
isolated platinum complex of a thiophosphinite-amino-
phosphane (route 1).
The 31P NMR of 1a shows two doublets with satel-
lites, at 46.3 ppm (1JPtP 3988 Hz), due to the coordi-
nated aminophosphane group, and at 39.2 ppm
(3771 Hz) for the thiophosphinite. Comparing these
data with the corresponding set of the free ligand (41.9
and 31.1 ppm, respectively), it can be concluded that
the observed coordination shift is small for both phos-
phorus nuclei.
prepared from serin methyl ester [3] (Table 1), it is pos-
sible to notice that the chemical shift of the PS group is
about 86 ppm highfield in the free ligand and 55 ppm in
the Pt complex with respect to the corresponding PO:
this is probably due to the greater electronegativity of
oxygen which makes the oxygen-bonded phosphorus
more deshielded than the sulfur-bonded one.
The 1H NMR of 1a appears complicated for the pres-
ence of four inequivalent protons in the aliphatic zone:
CHN, NH and the two diastereotopic CH2 protons.
The correct assignment, reported in the Experimental,
1
has been allowed by a H COSY experiment.
The signal at 2.9 ppm, which disappears after D2O
addition, is due to the NH coupled with Pt
(3JPtH = 20 Hz). The diastereotopic protons Ha and
Hb in b at the chiral carbon appear as doublets of dou-
blets of doublets, because they are both coupled with the
adjacent phosphorus with different coupling constants
It is possible to obtain complex 1a also through a
‘‘template synthesis’’ (route 2) as we have previously
proposed for diphosphinites, AMPP and BAMP [2,3]:
in a single process, the chlorodiphenylphosphane reacts
with [PtCl2(1,5-COD)] giving the labile intermediate cis-
3
(3JHaP = 9.3 Hz and JHbP = 24.5 Hz).
1
[PtCl2(PPh2Cl)2] (31P NMR: 73.4 ppm, JPtP 4069 Hz
[3]). The addition of cysteine methyl ester hydrochloride
and 3 eq. of Et3N gives 1a.
2.2. Selective formation of S–P bond on cystein methyl
ester hydrochloride
We previously proposed the template procedure with
the aim to stabilise easily decomposable ligands like
diphosphinites: because on the contrary ligand 1 was
found to be quite stable (after 3 days in solution no
decomposition was observed by 31P NMR), in this case
The reaction of L-cysteine methyl ester hydrochloride
with 1 eq. of chlorodiphenylphosphane and 2 eq. of
Et3N gives the amino-thiophosphinite 2 with complete
regioselectivity. The 31P NMR shows a single peak at

P. Bergamini et al. / Inorganica Chimica Acta 358 (2005) 2031–2039
2033
Table 1
31P NMR data (CDCl3 solutions)
1
1
PN d (ppm) JPt–P (Hz)
PX (X = S, O) d (ppm) JPt–P (Hz)
2JPP (Hz)
1
1a
41.9
46.3, JPt–P 3988
31.1
39.2, JPt–P 3771
1
1
15
12
Serin AMPP [3]
Serin AMPP Pt complex [3]
42
43.5, JPt–P 3887
117
94.7, JPt–P 4104
1
1
30.8 ppm. The same reaction, using 1 eq. of Et3N, gives
the N protonated form of 2, (2H+).
appears as a sharp single peak in a close position
(32.3 ppm, 3739 Hz). If further Et3N is added to a
CDCl3 solution of 2aH+, the deprotonation gives rise
to the re-appearance of the broad signal at 28 ppm.
S
PPh2
*
PPh2Cl
2 Et3N
2.3. Preparation of a dithiophosphinite from ethyl-1,2-
dithiopropionate
MeOOC
NH2
SH
2
When (+/À)-ethyl-1,2-dithiopropionate is treated
with 2 equivalents of PPh2Cl in the presence of Et3N,
the new dithiophosphinite 3 is obtained. The two phos-
phorus nuclei of the free ligand appear as two singlets at
29.5 and 24.7 ppm, the expected zone for diphenylthio-
phosphinites. The addition of platinum gives the imme-
diate formation of complex 3a (44.2 ppm, 3812 Hz;
*
+
MeOOC
NH3
PPh2Cl
Et3N
S
PPh2
*
+
MeOOC
NH3
2 H+
2
40.5 ppm, 3823 Hz, JPP 12 Hz).
S PPh2
S PPh2
SH
SH
Ligand 2 reacts with [PtCl2(1,5-COD)] in a 2:1 ratio
to give complex 2a acting as a phosphorus donor
monodentate ligand.
2
PPhCl
Et N
*
*
2
3
EtOOC
EtOOC
3
Ph2
P
NH2
S
S
Cl
Cl
MeOOC
MeOOC
Ph2
P
[PtCl (1,5-COD)]
2
*
*
Pt
Cl
Cl
S
PPh2
S
S
*
[PtCl2(1,5-COD)]
COD
Pt
P
EtOOC
2
*
Ph2
COD
P
Ph2
MeOOC
NH2
3a
NH2
2
2a
The 1H NMR of 3a shows a multiplet at 4.3 ppm, due
to the overlapping of the ethyl CH2 and the CHCOO
signals. The diastereotopic protons of CH2S appear as
a complicated signal at 3.5 ppm.
Also in this case, the addition of an excess of TBACN
to a CDCl3 solution of 3a gives ligand 3, as proved by
the appearance of two singlets at 29.7 and 25.0 ppm in
31P NMR.
Solutions of 3 and of 3a in CH2Cl2 were stored at
room temperature for five days. A check by 31P NMR
after this time showed complete decomposition of 3,
while the spectrum of 3a appeared unchanged.
In solution, the 31P NMR of 2a shows a broad singlet
at 28 ppm (3608 Hz). The broadening is probably due to
an equilibrium between the open form and a bis-chelate
with two six-membered rings.
2+
COOMe
*
S
NH2
MeOOC
MeOOC
Ph2
P
*
*
Cl
Cl
Ph2P
Ph2P
S
NH2
NH2
S
S
2 Cl -
Pt
Pt
P
Ph2
NH2
*
COOMe
2a
2.4. Preparation of a dithiophosphinite from meso-
dimethyl-2,3-dithiosuccinate
This hypothesis is confirmed by the observation that
when the same reaction is performed with the N-proton-
ated form of 2, the signal of the corresponding complex
The commercial product meso-2,3-dithiosuccinic acid
has been transformed into its dimethyl ester by a selec-
tive procedure which introduces the methyl groups on

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P. Bergamini et al. / Inorganica Chimica Acta 358 (2005) 2031–2039
the two carboxylates excluding the two SH groups. This
product can be obtained by refluxing the acid in metha-
nol with an excess of acetyl chloride. The immediate
reaction between MeOH and acetyl chloride generates
the hydrochloric acid required for the esterification.
The resulting dimethyl ester has been characterised by
isopropyltartrate (Table 2) previously prepared and
characterised in our laboratory [2].
Either for the oxygen or the sulfur containing ligands
or the coordination shift is about 23 ppm, but the Pt
bonding shifts the ligand signal downfield when X = S
and upfield when X = O.
By slow stratification of Et2O over CH2Cl2 solutions,
crystals suitable for structure diffractometric analysis
were obtained for 4a (Fig. 1 and Table 3). To our knowl-
edge, this is the first reported structure of a platinum
coordinated dithiophosphinite.
The complex displays a slightly distorted square pla-
nar geometry with the metal centre bonded to two chlo-
ride and two phosphorus atoms belonging to the
ligands. The maximum deviation from the plane is
1
comparison of its H NMR with the reported data [10].
The treatment of this ester with 2 equivalents of
PPh2Cl gives the diphenylphosphinite 4 (31P NMR sin-
gle signal at 24.9 ppm), which is converted into its Pt
complex 4a by adding an equimolar amount of
[PtCl2(1,5-COD)].
1
In addition to, the Ph and Me signals, the H NMR
of 4a shows the signal of the CH a to COOMe and to
sulfur as a doublet at 4.7 ppm, due to the coupling to
phosphorus (3JHP = 7.3 Hz).
Solutions of 4 and of 4a in CH2Cl2 were stored at
room temperature for five days. A check by 31P NMR
after this time showed complete decomposition of 4,
while the spectrum of 4a appeared unchanged.
˚
0.227(2) A for Cl1 atom. The seven chelate ring presents
a twisted-chair conformation.
Every attempt to obtain 4a by a template synthesis,
reacting the meso-dimethyl-2,3-dithiosuccinate with cis-
[PtCl2(PPh2Cl)2], both with and without Et3N, gave
SH
SH
S
S
PPh2
PPh2
SH
SH
MeOOC
MeOOC
MeOOC
MeOOC
HOOC
MeOH
2 PPh Cl
2
*
*
*
*
*
+
H
*
HOOC
4
-
CN
Ph2
P
S
S
MeOOC
MeOOC
Cl
Cl
[PtCl (1,5-COD)]
*
*
2
Pt
P
Ph2
COD
4a
Once more, the free ligand can be obtained from the
complex by treatment of a CDCl3 solution with an ex-
cess of TBACN, as proved by 31P NMR observation.
The 31P NMR data of 4 and its Pt complex 4a can be
compared with the oxygen analogues deriving from di-
complex 5a (31P NMR 87.4 ppm, 3108 Hz in CH2Cl2)
1
promptly identified by the small value of JPtP, charac-
teristic of phosphorus trans to sulfur and confirmed by
the observation of a singlet with satellites at 4.2 ppm
3
1
with JPtH = 44 Hz in H NMR.
Table 2
31P NMR data (CDCl3)
Ph2
P
X
X
X
X
PPh2
PPh2
MeOOC
MeOOC
MeOOC
Cl
Cl
*
*
*
*
Pt
MeOOC
P
Ph2
X = O, di-isopropyltartrate-PP
X = S, 4
1
PX (X = S, O) d (ppm) JPt–P (Hz)
4
4a
24.9
47.5, JPt–P 3822
1
Di-isopropyltartrate PP [2]
Di-isopropyltartrate-PP, Pt complex [2]
119
94.7, JPt–P 4003
1

P. Bergamini et al. / Inorganica Chimica Acta 358 (2005) 2031–2039
Ph2
2035
S
P
MeOOC
Cl
Cl
*
*
Pt
MeOOC
S
P
Ph2
SH
SH
MeOOC
MeOOC
ClPh2P
ClPh2P
Cl
Cl
*
*
4a
+
Pt
S
COOMe
COOMe
ClPh2P
ClPh2P
*
*
Pt
S
5a
H2O
S
S
COOMe
COOMe
HOPh2P
HOPh2P
*
*
Pt
5aOH
This experiment shows that, in contrast with the re-
sult with vicinal diols, in the case of vicinal dithiols,
the nucleophilic substitution at platinum is preferred
to nucleophilic substitution at phosphorus. This is not
surprising on the basis of the great affinity of platinum
II, a soft acid, for sulfur (soft base) [11].
The addition of water to a solution of 5a in CH2Cl2
causes the hydrolysis of the two coordinated chlorodi-
phenylphosphane with formation of the corresponding
PPh2OH complex, 5aOH, whose 31P NMR shows a sin-
1
glet at 80 ppm with JPtP = 3193 Hz.
The addition of a second equivalent of meso-di-
methyl-2,3-dithiosuccinate to a solution of 5a in CH2Cl2
does not cause any reaction without a base. The further
addition of an excess of Et3N causes decomposition with
formation of an unidentified main species showing a sin-
glet with satellites at 65.6 ppm (3134 Hz).
2.5. Preparation of phosphorated ligands from DL-1,4-
dithiothreitol
Fig. 1. ORTEP view of 4a showing the thermal ellipsoids at 30% level
of probability.
In the attempt to complete the series of the above de-
scribed products containing PN/PS (1) and PS/PS (3 and
4) bonds, we planned to prepare a ligand containing a
P–S and a P–O bond in the same molecule.
Table 3
˚
Selected bond distances (A) and angles (ꢁ) for 4a
To this purpose, we treated the commercial DL-1,4-
dithiothreitol with 4 equivalents of chlorodiphenylphos-
phane in the presence of 4 equivalents of Et3N trying to
obtain a tetradentate PS/PO ligand through the com-
plete phosphorylation of the SH and OH groups, but
unfortunately the result of this reaction is an extended
decomposition with formation of many phosphorus
containing products: it was possible to identify
PPh2PPh2 as a singlet at À15 ppm and its oxidation
product PPh2PPh2O (2 doublets at 35 and À23 ppm)
Pt1–Cl1
Pt1–Cl2
Pt1–P1
Pt1–P2
P1–S1
2.338(1)
2.344(1)
2.248(1)
2.243(1)
2.108(1)
2.109(1)
1.823(4)
1.817(5)
1.533(5)
Cl1–Pt1–Cl2
Cl1–Pt1–P1
Cl1–Pt1–P2
Cl2–Pt1–P1
Cl2–Pt1–P2
P1–Pt1–P2
Pt1–P1–S1
Pt1–P2–S2
P1–S1–C1
P2–S2–C2
87.67(5)
168.30(4)
91.43(4)
83.98(4)
176.71(4)
96.44(4)
119.78(5)
116.98(5)
102.3(1)
105.2(1)
P2–S2
S1–C1
S2–C2
C1–C2

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P. Bergamini et al. / Inorganica Chimica Acta 358 (2005) 2031–2039
[12]. A group of signals was found around 30 ppm, typ-
ical of thiophosphinites.
Several attempts to obtain the tetraphosphorated li-
gand in a coordinated form by adding PPh2Cl to a solu-
tion of 6a gave rise to many phosphorated species, no
one containing a phosphorus (III)-oxygen bond.
S
O
O
S
PPh2
PPh2
PPh2
PPh2
*
*
3. Conclusion
SH
OH
OH
SH
A group of new phosphorus(III) ligands, containing
P–S bonds and chiral centres, has been prepared and
characterised in the stable Pt(II) coordinated form.
The efficiency in homogeneous catalysis of the opti-
cally active form of these ligands will be investigated.
*
*
+
4 PPh2Cl
decomposition
In order to understand and avoid this decomposition
4. Experimental
process, we repeated the above reaction by adding pro-
gressively four one-equivalent aliquots of PPh2Cl and
checking 31P NMR after each addition.
All reactions and manipulations were routinely per-
formed under a dry nitrogen atmosphere by using
standard Schlenk-tube techniques. Tetrahydrofuran
was bi-distilled over LiAlH4, while CH2Cl2 was purified
by distillation over CaCl2. Triethylamine was distilled
and stored over KOH. CDCl3, used as solvent for
After the first addition, the spectrum shows a singlet at
31.7 ppm corresponding to the formation of the species
with a single SP bond. The second equivalent gives a spe-
cies with a single signal close to the previous, 29.5 ppm,
assignable to the dithiophosphinic species 6. After the
addition of the third equivalent, the signals of the above
mentioned decomposition products start to appear and
increase after the fourth aliquot. The formation of a PO
bond, characterised by a signal in the downfield zone of
the spectrum (around 90–100 ppm), was not observed.
˚
NMR spectra, was dried over molecular sieves (4 A).
PPh2Cl (d = 1.23 g mlÀ1) was purified by distillation
under nitrogen and checked by 31P NMR before use.
All the other solvents and chemicals were reagent grade
and were used as received from commercial suppliers.
1
1H and 31P NMR spectra (always H decoupled) were
SH
OH
OH
SH
S
PPh2
S
PPh2
PPh2
PPh2Cl
PPh2Cl
*
*
OH
OH
SH
PPh2Cl
OH
OH
S
*
*
*
*
PPh2Cl
Decomposition
6
When 6 was produced in solution and an equimolar
amount of [PtCl2(1,5-COD)] was added, the NMR of
the resulting mixture showed a group of close signals
with satellites around 33 ppm. The magnitude of the
1JPtP of 3822 Hz indicates that the geometry is cis and
that the phosphorus donors are trans to chloride. We be-
lieve that the signals belong to a group of polymeric spe-
cies with 6 acting as a bridging ligand (6a), the eight
atoms chain of ligand 6 being too long to allow it to
act as a chelating bidentate ligand.
recorded on a Bruker AC200 spectrometer operating
at 200.13 MHz (1H) and 81.01 MHz (31P), respectively.
Peak positions are given in ppm relative to tetrameth-
ylsilane (1H) and to external 85% H3PO4 (1P). Elemental
analyses (C, H, N) were performed using a Carlo Erba
model 1106 elemental analyser. Optical rotations were
measured on a Perkin Elmer 241 at 25 ꢁC.
Literature methods were used for the preparation of
[PtCl2(1,5-COD)] [13].
Ligand 1 has been prepared following the procedure
described by Woollins and co-workers [9].
OH
Ph2
P
Ph2
P
4.1. Preparation of 1a
S
S
PPh2
Pt
PPh2
Pt
*
S
S
*
HO
n
4.1.1. Route 1
To a solution containing 0.087 g of
L-cysteine methyl
ester hydrochloride (0.508 mmol) in 5 ml of CH2Cl2,
Cl
Cl
Cl
Cl
6a

P. Bergamini et al. / Inorganica Chimica Acta 358 (2005) 2031–2039
2037
246 ll of Et3N (1.777 mmol; d = 0.73 g/ml) was added
under stirring. A second solution of PPh2Cl (182 ll,
1.016 mmol; d = 1.23 g/ml) in 3 ml of CH2Cl2 was added
dropwise to the previous at 0 ꢁC. After 3 h, the identity
of ligand 1 was checked by 31P NMR (2 singlets at 31.1
and 41.9 ppm) and 0.190 g of [PtCl2(1,5-COD)]
(0.508 mmol) was added. The mixture immediately
turned yellow. After 10 min, the organic solution was
extracted with water (3 · 10 ml).
4.3. Preparation of ligand 3 and its platinum complex 3a
To a solution containing 0.121 g of ethyl-2,3-dimer-
captopropionate (0.728 mmol) in 10 ml of twice distilled
CH2Cl2, 202 ll di Et3N (1.455 mmol; d = 0.73 g/ml) and
261 ll of PPh2Cl (1.455 mmol d = 1.23 g/ml) were added
in sequence under stirring at 0 ꢁC. After 15 min, the for-
mation of 3 was observed by 31P NMR (2 singlets, 24.7
and 29.5 ppm) and 0.272 g of [PtCl2(1,5-COD)]
(0.728 mmol) was added. The solution immediately
turned yellow and after 10 min it was extracted with
water (3 · 10 ml).
The organic layer was dried over Na2SO4 and then
taken to dryness under vacuum to give pure 1a as a yel-
low solid (0.204 g; 52%).
The separated organic layer was then dried over
Na2SO4 and then taken to dryness under vacuum to give
pure 3a as a yellow solid (0.370 g; 64%).
4.1.2. Route 2
To
a
solution of [PtCl2(1,5-COD)] (0.190 g,
0.508 mmol) in CH2Cl2 (8 ml), PPh2Cl (182 ll,
1.016 mmol, d = 1,23 g/ml) was added dropwise under
stirring at room temperature. The formation of the
intermediate complex cis-[PtCl2(PPh2Cl)2] was checked
C29H28Cl2O2P2PtS2 (800): Anal. Calc. C, 43.49; H,
3.53; S, 8.01. Found: C, 43.99; H, 3.95; S, 8.28%.
1H NMR (200 Mz, CDCl3, 25 ꢁC): d = 1.2 (t,
2JHH = 6.7 Hz, 3H, CH3), 3.5 (m, 2H, CH2S), 4.2 (m,
2 + 1H, CH2O + CHS), 7.2–7.9 (m, 20H, Ph) ppm.
31P NMR (81.01 MHz, CDCl3, 25 ꢁC): d = 40.5 (d,
1
by 31P NMR: 73.4 ppm, JPtP 4069 Hz [3].
The addition of triethylamine (1.777 mmol;
d = 0.73 g/ml) and 0.087 g (0.508 mmol) of
1
2
L
-cysteine
PA, JPt–P = 3823 Hz, JPAPB = 12 Hz), 44.2 (d, PB,
2
methyl ester hydrochloride gave a yellow solution. After
3 h, the solution was treated as above, giving a yellow
solid (0.260 g; 67%).
1JPt–P = 3812 Hz, JPAPB = 12 Hz) ppm. After the addi-
tion of an excess of TBACN, the signals of the free li-
gand were detected: 25.0 ppm (s) and 29.7 ppm (s).
C28H27Cl2NO2P2PtS (769): Anal. Calc. C, 43.69; H,
3.54; N, 1.82; S, 4.17. Found: C, 43.24; H, 3.52; N,
1.70; S, 4.57%.
4.4. Preparation of ligand 4 and its platinum complex 4a
1H NMR (200 Mz, CDCl3, 25 ꢁC) + 1H/1H COSY
4.4.1. Step i: preparation of meso-dimethyl-2,3-
dithiosuccinate
(400 Mz, CDCl3, 25 ꢁC): d 2.9 (dd with sat, 2JHP = 4 Hz,
3
3JHH = 6 Hz, JHPt = 20 Hz, 1H, NH), 3.2 (ddd,
In a round-bottomed flask, 0.7 g (4.7 mmol) of meso-
dimethyl-2,3-dithiosuccinic acid was suspended in 30 ml
of methanol and 5 ml of acetyl chloride was added at
0 ꢁC. The mixture was then refluxed and two further ali-
quots of 1 ml of acetyl chloride were added after 30 and
60 min. After further 30 min, the solution was taken to
dryness under vacuum leaving the meso-dimethyl-2,3-
dithiosuccinate as a solid product (0.837 g, 4.7 mmol,
100% yield).
2
3
3JHP = 24.5 Hz, JHH = 14 Hz, JHH = 4.4 Hz, 1H,
2
CHHS), 3.8 (s, 3H, CH3); 3.85 (ddd, JHH = 14 Hz,
3JHP = 9.3 Hz, JHH = 4.4 Hz, 1H, CHHS); 3.95 (ddd,
3
3JHH = 6 Hz, 3JHH = 4.4 Hz, 3JHH = 4.4 Hz, 1H,
CHN); 7.2–8.0 (m, 20H, Ph).
31P NMR (81.01 MHz, CDCl3, 25 ꢁC): d = 39.2 (d,
PA, JPt–P = 3771 Hz), 46.3 (d, PB, JPt–P = 3988 Hz)
1
1
2
ppm; JPAPB = 15 Hz. After the addition of an excess
of TBACN to this solution, the free ligand signals were
observed (31.1 and 41.9 ppm).
1H NMR (200 Mz, CDCl3, 25 ꢁC): d = 2.3 (dd,
3
3JHH = 3 Hz, 2H, SH), 3.6 (dd, JHH = 3 Hz, 2H, CH),
3.8 (s, 6H, CH3).
[a]D25 = À8.4ꢁ (C = 0.51, CH2Cl2).
4.2. Preparation of ligand 2 and its platinum complex 2a
4.4.2. Step ii: preparation of 4 and 4a
The procedure is the same as the above described for
3 and 3a using 0.056 g of meso-dimethyl-2,3-dithiosucci-
nate (0.267 mmol) in CH2Cl2, 74 ll di Et3N
(0.534 mmol; d = 0.73 g/ml) and 96 ll of PPh2Cl
(0.534 mmol d = 1.23 g/ml). After 15 min, the formation
of 4 was observed by 31P NMR (one singlet at 24.9 ppm)
and 0.100 g of [PtCl2(1,5-COD)] (0.267 mmol) was
added. The solution immediately turned yellow and
after 15 min it was extracted with water (3 · 10 ml).
The organic layer was dried over Na2SO4 and then
taken to dryness under vacuum to give pure 4a as a yel-
low solid (0.148 g; 66%).
To a solution containing 0.092 g of L-cysteine methyl
ester hydrochloride (0.535 mmol) in 10 ml of CH2Cl2,
74 ll of Et3N (0.535 mmol; d = 0.73 g/ml) and 96 ll di
PPh2Cl (0.535 mmol; d = 1.23 g/ml) were added in se-
quence under stirring at 0 ꢁC. After 3 h, the identity of
ligand 2H+ was checked by 31P NMR (s, 32.1 ppm),
and 0.100 g of [PtCl2(1,5-COD)] (0.267 mmol) was
added. The mixture immediately turned yellow and the
formation of 2aH+ was observed by 31P NMR.
31P NMR (81.01 MHz, CDCl3, 25 ꢁC): d = 32.3 (s,
1JPt–P = 3739 Hz) ppm.

2038
P. Bergamini et al. / Inorganica Chimica Acta 358 (2005) 2031–2039
C30H28Cl2O4P2PtS2 (844): Anal. Calc. C, 42.64; H,
3.34; S, 7.60. Found: C, 42.35; H, 3.23; S, 7.43%.
tracted with water (3 · 10 ml) in order to eliminate
NEt3HCl. The organic layer was finally dried over
Na2SO4 and then taken to dryness under vacuum to give
pure 5aOH as a pale yellow solid. (0.187 g; 87%).
C30H30O6P2PtS2 (807): Anal. Calc. C, 44.6; H, 3.72;
S, 7.93. Found: C, 43.9; H, 3.82; S, 8.67%.
1H NMR (200 Mz, CDCl3, 25 ꢁC): d = 3.7 (s, 6H,
CH3); 4.7 (d, 2H, JHP = 7.3 Hz, CH); 7.2–7.9 (m,
3
20H, Ph).
31P NMR (81.01 MHz, CDCl3, 25 ꢁC): d = 48.1 (s,
1JPt–P = 3806 Hz) ppm. After the addition of an excess
of TBACN, the signal of the free ligand was detected
at d = 24.8 (s) ppm.
1H NMR (200 Mz, CDCl3, 25 ꢁC): d = 3.7 (s, 6H,
3
CH3); 4.2 (s, JPtH = 44 Hz, 2H, CH); 7.1–7.9 (m, 20H,
Ph).
31P NMR (81.01 MHz, CDCl3, 25 ꢁC): d = 80.0 (s,
4.5. X-ray crystal structure determination of 4a
1JPt–P = 3193 Hz) ppm.
X-ray diffraction data for compound 4a were col-
lected on a Nonius Kappa CCD diffractometer, at room
temperature (T = 295 K), with graphite monochromated
4.7. Preparation of ligand 6 and its platinum complex 6a
To a solution containing 0.100 g of DL-1,4-dithiothre-
itol (0.648 mmol) in 15 ml di CH2Cl2, 180 ll di Et3N
(1.296 mmol; d = 0.73 g/ml) and 232 ll of PPh2Cl
(1.29 mmol; d = 1.23 g/ml) were added in sequence un-
der stirring at 0 ꢁC. The formation of 6 was observed
by 31P NMR (singlet at 29.4 ppm) and 0.242 g of
[PtCl2(1,5-COD)] (0.648 mmol) was added. The solution
immediately turned yellow and after 3 h it was extracted
with water (3 · 10 ml), the organic layer was finally
dried over Na2SO4 and then taken to dryness under vac-
uum to give pure 6a as a yellow solid (0.29 g; 56%).
C28H28Cl2O2P2PtS2(788): Anal. Calc. C, 42.63; H,
3.58; S, 8.14. Found: C, 42.33; H, 3.83; S, 9.13%.
31P NMR (81.01 MHz, CDCl3, 25 ꢁC): d = ca.
˚
Mo Ka radiation (k = 0.7107 A) and corrected for Lor-
entz, polarization and absorption (SORTAV) [14] ef-
fects. The structure was solved by direct methods (SIR
97) [15] and refined (SHELXL-97) [16] by full matrix least
squares with anisotropic non-H and hydrogen atoms on
calculated positions, riding on their carrier atoms.
Crystal data: 4a, C30H28Cl2O4P2PtS21/2CH2Cl2; tri-
ꢀ
clinic, space group P1, a = 10.1369(1), b = 12.1207(2),
˚
c = 16.1039(2) A, a = 92.579(1)ꢁ, b = 107.532(1)ꢁ, c =
3
À3
.
˚
114.168(1)ꢁ, V = 1688.83(4) A , Z = 2, Dc = 1.744 g cm
Intensity data collected with h 6 30ꢁ; 9748 independent
reflections measured; 8637 reflections observed
[I > 2r(I)]. Final R (observed reflections) = 0.041 and
Rw (all reflections) = 0.106. The crystal contains dichl-
oromethane, disordered around centres of symmetry,
in a 1:2 ratio with the Pt complex.
1
33 ppm (several close signals with satellites, JPt–P = ca.
3820 Hz).
An ORTEP [17] view of the structure of 4a is given in
Fig. 1 and a selection of bond distances and angles is re-
ported in Table 3.
Acknowledgement
Complete crystallographic data (excluding structural
factors) for the structure in this paper have been depos-
ited with the Cambridge Crystallographic Data Centre
as supplementary publication number CCDC 250106.
These data can be obtained, free of charge, via
www.ccdc.cam.ac.uk/conts/retrieving.html or on appli-
cation to CCDC, 12 Union Road, Cambridge CB2
1EZ, UK [fax: +44(0) 1223 336033 or e-mail:
deposit@ccdc.cam.ac.uk].
We thank Dr. Remo Guerrini, Pharmaceutical Sci-
ence Department of University of Ferrara, for his sup-
port to this work.
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