A palladium complex with a new hemilabile amino- and sulfur-containing phosphinite ligand as an efficient catalyst for the Heck reaction of aryl bromides with styrene. The effect of the amino group

Article abstract of DOI:10.1016/S0040-4020(03)00474-5

A palladium complex with a new hemilabile amino- and sulfur-containing phosphinite ligand has been synthesised and its crystal structure determined. This system efficiently catalyses the Heck reaction of aryl bromides with styrene at 130°C after 24h, with turnover numbers of up to 100000 and with a selectivity towards trans-stilbenes ranging from 91.5 to 96.3%. The analogous sulfur-containing phosphinite without the amino group has also been synthesised and subjected to the Heck reaction. The constructive role of the amino group on the formation of the P,S-chelate palladium complex as well as in the Heck reaction is discussed.

Full text of DOI:10.1016/S0040-4020(03)00474-5

Tetrahedron 59 (2003) 3467–3473
A palladium complex with a new hemilabile amino- and
sulfur-containing phosphinite ligand as an efficient catalyst for the
Heck reaction of aryl bromides with styrene. The effect of the
amino group
a
b
c
Ioannis D. Kostas,a Barry R. Steele, Aris Terzis and Svetlana V. Amosova
,
,
*
*
aNational Hellenic Research Foundation, Institute of Organic and Pharmaceutical Chemistry, Vas. Constantimou 48, 116 35 Athens, Greece
bInstitute of Materials Science, NCSR Democritos, 153 10 Aghia Paraskevi Attikis, Greece
cFavorsky Irkutsk Institute of Chemistry, Siberian Branch of Russian Academy of Sciences, 1 Favorsky Street, 664033 Irkutsk,
Russian Federation
Received 23 January 2003; revised 27 February 2003; accepted 21 March 2003
Dedicated to Professor Dr Manfred T. Reetz on the occasion of his 60th birthday and in recognition of his important contributions to chemistry
Abstract—A palladium complex with a new hemilabile amino- and sulfur-containing phosphinite ligand has been synthesised and its crystal
structure determined. This system efficiently catalyses the Heck reaction of aryl bromides with styrene at 1308C after 24 h, with turnover
numbers of up to 100000 and with a selectivity towards trans-stilbenes ranging from 91.5 to 96.3%. The analogous sulfur-containing
phosphinite without the amino group has also been synthesised and subjected to the Heck reaction. The constructive role of the amino group
on the formation of the P,S-chelate palladium complex as well as in the Heck reaction is discussed. q 2003 Elsevier Science Ltd. All rights
reserved.
1. Introduction
The palladium-catalysed arylation of alkenes, nowadays
known as the Heck reaction, is one of the most versatile
tools of organic chemistry for C–C bond forming
reactions.1 The reactivity decreases drastically in the order
ArI.ArBr.ArCl and, for that reason, aryl bromides and
chlorides, while being cheaper and more readily available
and therefore much more useful substrates to synthetic
chemists, often do not react efficiently. In recent years,
however, aryl bromides and chlorides have been success-
fully applied using a variety of catalytic systems involving,
for example, several types of phosphorus-free ligands,2
monodentate phosphorus ligands,3 phosphorus or phos-
phorus–heteroatom bi- or polydentate ligands,4 or
traditional Heck coupling catalysts combined with
additives5 or with new techniques.6
Figure 1.
reported the synthesis of several functionalised hemilabile
P,N-, P,N,P- and N,P,N-ligands (1–6) and their application
in rhodium-catalysed hydroformylation, hydroamino-
methylation and hydrogenation (Fig. 1).9–12
As an extension of this research, we report here the
synthesis and crystal structure of a palladium complex with
a new hemilabile amino- and sulfur-containing phosphinite
ligand. This system was found to efficiently catalyse the
Heck reaction of aryl bromides with styrene. In order to
investigate the influence of the amino group on the catalyst
behaviour, we have also synthesised the analogous sulfur-
containing phosphinite without the amino group. The effect
of the amino group on the formation of the palladium
complex as well as in the Heck reaction is discussed.
Although phosphinites as ligands in homogeneously
The improved catalytic activity of transition metal com-
plexes with hemilabile ligands has been extensively
reviewed.7 Up to now, however, the use of such ligands in
the Heck reaction has been limited.4j,8 We have recently
Keywords: Heck reaction; hemilabile ligand; P,S-ligand; phosphinite;
palladium complex; crystal structure.
*
Corresponding authors. Tel.: þ30-210-7273878; fax: þ30-210-7273877;
e-mail: ikostas@eie.gr (I.D.K.); bsteele@eie.gr (B.R.S.)
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00474-5

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I. D. Kostas et al. / Tetrahedron 59 (2003) 3467–3473
Scheme 2.
Figure 2.
catalytic processes have been widely studied,11,13 their
application in the Heck reaction is limited to a palladium
bis(phosphinite) PCP–pincer complex 74c and to palladium
complex catalysis involving phosphinite-oxazoline ligands
8 derived from D-glucosamine14 (Fig. 2).
N(CH3)2 resonances which are in almost the same position
in both the complex and the free ligand, indicating the
absence of Pd–N interaction.
Yellow crystals of complex 16 suitable for X-ray crystal
structure determination were obtained by slow diffusion of
ether through a diluted solution of 16 in dichloromethane.
Its structure is shown in Figure 3. As shown in the crystal
structure, the ligand is coordinated to the metal in a P,S-
bidentate mode without any Pd–N interaction. The
coordination sphere around palladium can be regarded as
slightly distorted square planar (P–Pd–S, 95.41(2)8;
S–Pd–Cl(1), 81.16(3)8; Cl(1)–Pd–Cl(2), 91.51(3)8;
Cl(2)–Pd–P, 91.89(3)8). The Pd–P and Pd–S distances of
2. Results and discussion
2.1. Synthesis of the ligands
The synthesis of ligands 14 and 15 is outlined in Scheme 1.
The ligand precursor 14 was prepared in a multistep
procedure from N,N-dimethyl-o-toluidine (9), in an overall
yield of 58%. ortho-Metallation of 9 by n-BuLi and
subsequent quench with dimethyl disulfide yielded the
thioether 10, which was then subjected to metallation at the
benzylic carbon with n-BuLi/TMEDA and subsequent
reaction with ethylene oxide to give the functionalised
alcohol 12. The phosphinite ligand 14 was prepared by
hydrogen abstraction of 12 using n-BuLi and subsequent
reaction of the resulting alkoxide with ClPPh2. Phosphinite
15 was prepared by the same procedure from benzyl methyl
sulfide (11) in an overall yield of 53%.
˚
2.231(1) and 2.297(1) A, respectively, have normal values,
and the difference in bond lengths between the Pd–Cl(1)
˚
trans to P (2.369(1) A) and Pd–Cl(2) trans to S
˚
(2.292(1) A) is the result of the greater structural trans
influence of phosphorus compared to sulfur donor.4j
Figure 3. ORTEP drawing of palladium complex 16.
Unfortunately, all attempts to synthesise an analogous
chelate palladium complex with ligand 15 were unsuccess-
ful. Treatment of PdCl2(NCPh)2 with 1 equiv. of ligand 15,
as described above for the synthesis of 16, led to a yellow
solid, the NMR data of which need some comments. The
SCH3 group gave two singlet peaks at d 2.29 and 1.97 in the
1H NMR spectrum, and also two singlet peaks at d 21.93 and
15.24 in the 13C NMR spectrum. The SCH3 resonances at
low field indicate the existence of a coordinated group while
the higher field resonances which have shifts comparable to
those of the free ligand, indicate the presence of non-
coordinated groups. In addition, the 13C NMR spectrum
displays two peaks for each of the non-aromatic carbons and
the 31P NMR spectrum exhibits two singlets at d 111.12 and
113.03, which are at higher field compared to the chemical
shift of 119.75 for the P,S-chelate palladium complex 16,
indicating that an analogous chelation for the ligand 15 is
Scheme 1. Reagents and conditions: (i) n-BuLi, Et2O, room temperature to
358C; (ii) Me2S2, 08C to room temperature; (iii) n-BuLi/TMEDA,
methylcyclohexane, 2108C; (iv) ethylene oxide, Et2O, 2108C to room
temperature; (v) n-BuLi, THF, 2788C to room temperature; (vi) Ph2PCl,
THF, 08C to room temperature.
2.2. Synthesis and characterization of the palladium
complexes
Treatment of PdCl2(NCPh)2 in a dichloromethane solution
with 1 equiv. of ligand 14 yielded the palladium complex 16
1
in high yield (Scheme 2). The solution H and 13C NMR
spectra indicated that the ligand is P,S-bonded and that the
nitrogen is situated away from the coordination sphere
around palladium. The SCH3 resonances are shifted to low
field compared to those in the free ligand, in contrast to the

I. D. Kostas et al. / Tetrahedron 59 (2003) 3467–3473
3469
2.3. Heck reaction
Complex 16 was applied to the Heck reaction of styrene
with several 4-substituted aryl bromides (from electron-rich
to electron-poor) in DMF at 1308C for 24 h, using AcONa as
base, and in the absence of any promoting additive such as
n-Bu4NBr (Scheme 4, Table 1). Since 16 is sensitive
towards air and moisture, the efficient exclusion of air and
the use of pure and dry solvent and Heck reactants was
necessary. Phosphinites are also known to be sensitive
towards alcohols and thus the application of 16 to the Heck
reaction of 4-bromophenol failed. Catalysis was performed
using a stock solution of 16, avoiding the separate in situ
addition of the palladium source and the ligand to the
reactants, following the procedure which has previously
been recommended by Shaw and Perera for Pd-chelating
diphosphine catalysts.4a The advantages of using
chelating ligands in the Heck reaction have been reviewed
elsewhere.1a,b
Scheme 3.
not present. These data indicate that treatment of PdCl2-
(NCPh)2 with 15 gives a mixture of two complexes for
which a seven-membered P,S-chelate ring must be
excluded. Since sulfur is coordinated to the metal in one
of these complexes and not in the other, the above-
mentioned observations, in combination with the elemental
analysis data, are consistent with the formation of the
dimeric structures 17 and 18 shown in Scheme 3. For
reasons which have not yet been understood, it is apparent
that the dimethylamino group on ligand 14 directs the
formation of the P,S-chelate complex and that this is not
possible for this system where the group is absent. This may
perhaps be due to steric effects.
The reaction was first performed using a 1:1000 catalyst–
aryl bromide molar ratio to ensure a higher yield process,
and then by decreasing the ratio to 1:100000. The
conversions were analysed by GC and, for some cases, the
yield refers to the isolated product, indicating the synthetic
value of our catalytic system. There was good selectivity
towards trans-stilbenes 21, ranging from 91.5 to 96.3%, and
it is noteworthy that side-products such as biphenyl were
absent or present only in traces. As expected, the catalytic
activity depends on the halide, while electron-withdrawing
groups on the aryl ring increase the reaction rate.1
catalyst–substrate ratio of 1:1000 leads to total yields of
A
Scheme 4.
Table 1. Heck reaction of aryl bromides with styrene catalysed by palladium complex 16
Entry
R
ArBr/Pd ratio
Yield (%)a
TONb
Selectivity
21 : 22 : 23
1
OMe
OMe
H
H
Cl
1000
100000
1000
100000
1000
100000
1000
100000
1000
13.3
5.7
133
5700
393
11600
904
81300
984
82600
1000
91.5 : – : 8.5
92.8 : – : 7.2
92.8 : 1.0 : 6.2
96.3 : 0.4 : 3.3
93.4 : 0.9 : 5.7
93.5 : 0.8 : 5.7
96.1 : 0.7 : 3.2
95.4 : 0.8 : 3.8
95.6 : 0.2 : 4.2
95.3 : 0.7 : 4.0
95.8 : 0.3 : 3.9
96.3 : 0.2 : 3.5
2
3c
4
39.3 (30)d
11.6
90.4
5
6
7
8
9c
10
11c
12c
Cl
81.3
98.4
CHO
CHO
CN
CN
NO2
NO2
82.6
100.0 (90)d
81.9
100.0 (94)d
100.0 (90)d
100000
1000
100000
81900
1000
100000
Reaction conditions: ArBr (1.0 mmol), styrene (1.5 mmol), AcONa (2.0 mmol), Pd complex 16 in DMF (1 mL), 1308C, 24 h.
Total GC yield of all isomers, based on the aryl bromide using decane as internal standard.
a
b
Turnover no. (TON)¼fraction of products (21þ22þ23)£substrate/Pd ratio.
c
The reaction was performed on a 10-fold scale.
Isolated yield.
d

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I. D. Kostas et al. / Tetrahedron 59 (2003) 3467–3473
Table 2. Heck reaction of aryl bromides with styrene catalysed by in situ PdCl2(PhCN)2 and ligand 14 or 15
Entry
Ligand
R
ArBr/Pd ratio
Yield (%)a
TONb
Selectivity
21 : 22 : 23
1c
2c
3
4
5
14
15
14
15
14
15
H
H
CHO
CHO
NO2
NO2
1000
1000
100000
100000
100000
100000
31.9 (25)d
27.1 (22)d
59.6
51.6
66.8
319
271
59600
51600
66800
55900
93.3 : 0.2 : 6.5
94.0 : 0.3 : 5.7
95.9 : 0.1 : 4.0
95.4 : 0.3 : 4.3
95.9 : 0.2 : 3.9
96.1 : – : 3.9
6
55.9
Reaction conditions: ArBr (1.0 mmol), styrene (1.5 mmol), AcONa (2.0 mmol), PdCl2(PhCN)2 and ligand (1:1) mixed in situ, DMF (1 mL), 1308C, 24 h.
Total GC yield of all isomers, based on the aryl bromide using decane as internal standard.
a
b
Turnover no. (TON)¼fraction of products (21þ22þ23)£substrate/Pd ratio.
c
The reaction was performed on a 10-fold scale.
Isolated yield.
d
13.3 and 39.3% for bromoanisole and bromobenzene,
respectively. At lower ratios for these substrates, the
reaction proceeds with TONs up to 5700 and 11600,
respectively. High activity was observed for activated aryl
bromides. A catalyst–substrate ratio of 1:1000 leads to high
or quantitative conversion of the aryl bromide, and with a
ratio of 1:100000, the reaction proceeds with TONs up to
100000. At lower ratios, even higher TONs are possible but
these were not optimised. Although the Heck reaction can
be performed at lower temperatures, 1308C is the best
reaction temperature for synthetic purposes. For some of the
activated bromides the reaction proceeds even at room
temperature without any additive but with considerably
lower reaction rates and, for that reason, are not of synthetic
importance.
3. Conclusions
In summary, a seven-membered chelate palladium complex
with a new hemilabile amino- and sulfur-containing
phosphinite ligand has been prepared. According to the
NMR data and its crystal structure, the ligand is bound to the
metal in a P,S-bidentate coordination mode without any
Pd–N interaction. This complex was found to efficiently
catalyse the Heck reaction of aryl bromides with styrene,
with high turnover numbers and a good selectivity towards
trans-stilbenes. Especially for the electron-poor aryl
bromides, a low catalyst loading as little as 0.001 mol%
was sufficient to mediate a high yield Heck reaction. The
low catalyst loading represents an environmentally friendly
procedure and could become important for industrial
processes. Attempts to synthesise a P,S-chelate palladium
complex with the analogous sulfur-containing phosphinite
ligand without the amino group failed, indicating the
constructive role of this group in the formation of a P,S-
chelation in this system, and this may be due to steric
effects. The catalytic activity of the latter ligand mixed in
situ with PdCl2(NCPh)2 was found to be lower compared
with the analogous amino-substituted ligand. The construc-
tive role of the amino group in catalysis is presumably due
to the stabilizing chelate effect of the complex, since a P,S-
chelation could not be achieved without this group, as well
as to the existence of nitrogen as an additional coordination
site as a stabilizing group during the course of the metal-
mediated reaction.
Since it was not possible to synthesise the analogous chelate
palladium complex with ligand 15, the catalytic activity of
the latter towards Heck reaction was investigated for a
representative range of substrates by mixing in situ PdCl2-
(NCPh)2 and 15 (1:1) in DMF, using the same reaction
conditions and reactant concentrations, as described above
for complex 16 (Table 2). For comparison purposes, the
Heck reaction was also performed my mixing in situ
PdCl2(NCPh)2 and ligand 14 (1:1) (Table 2). As expected,
and for reasons which have been mentioned elsewhere, the
catalytic activity of the in situ system PdCl2(NCPh)2/14 is
lower than complex 16.4a As shown in Table 2, the N,S-
phosphinite ligand 14 leads to higher TONs in comparison
with those obtained with the S-phosphinite ligand 15,
without a significance difference in the selectivity towards
trans-stilbenes. For the activated aryl bromides, the higher
activity of 14 compared to 15 is clear for a substrate–Pd
ratio of 100000:1. Although, the constructive role of the
amino group in catalysis has not been clarified, it is
presumably due to the stabilising chelate effect with ligand
14, since an analogous P,S-chelation with ligand 15 was not
possible. In addition, despite the absence of Pd–N
coordination in complex 16 or the system formed by mixing
ligand 14 and the palladium source in situ, the existence of
an additional coordination site as a stabilizing group during
the course of a metal-mediated reaction could improve the
catalytic efficiency of the complex. The higher activity of
complexes with nitrogen-containing phosphines in which
nitrogen is not bound to the metal compared with the
analogous ligands without nitrogen has previously been
noted by Reetz et al. for rhodium-catalysed hydroformyl-
ation.15
4. Experimental
4.1. General
Bis(benzonitrile)dichloropalladium was prepared according
to a literature procedure.16 n-BuLi was prepared from
lithium metal and n-BuCl in methylcyclohexane. All the
other reagents were commercially available. All prep-
arations and catalysis were carried out under argon by using
dry and degassed reagents and solvents. NMR: Bruker AC
300 (300.13, 75.47, and 121.50 MHz for H, 13C and 31P,
1
respectively); 1H and 13C NMR shifts were referenced to the
solvents and the 31P NMR shifts were referenced to
external 85% H3PO4 in D2O. The determination of the
CH, CH2 and CH3 carbons in the 13C NMR spectra was
performed by DEPT-NMR experiments. IR: Bruker
Equinox 55. ESI MS: Finnigan MAT TSQ 7000. GC-MS

I. D. Kostas et al. / Tetrahedron 59 (2003) 3467–3473
3471
(EI): Varian Saturn 2000 with a 30 m£0.25 mm DB5-MS
column. GC: Varian Star 3400 CX with a 30 m£0.53 mm
DB5 column. Elemental analyses for C, H, N: Perkin–
Elmer PE 2400 II.
(10), 45 (10). Anal. calcd for C12H19NOS: C, 63.96; H, 8.50;
N, 6.22. Found: C, 64.28; H, 8.75; N, 6.02.
4.2.3. 3-Methylthio-3-phenyl-1-propanol (13). Using a
similar procedure to that described for the synthesis of
12, compound 13 was prepared from benzyl methyl sulfide
11 (13.8 g, 100.0 mmol), in a yield of 76% (13.8 g,
75.8 mmol), as a colourless oil, bp 113–1148C (0.5 mbar).
IR (neat): n 3362, 3065, 3031, 2915, 2881, 1604, 1495,
1455, 1430, 1040, 960, 756, 699 cm21; 1H NMR (CDCl3): d
7.30–7.23 (m, 5H, Ar), 3.87 (t, 3J¼7.3 Hz, 1H, CH), 3.71–
3.68 (m, 1H, CH2), 3.61–3.55 (m, 1H, CH2), 2.30 (br s, 1H,
OH), 2.15–2.04 (m, 2H, CH2), 1.86 (s, 3H, SCH3); 13C{1H}
NMR (CDCl3): d 141.89, 128.47, 127.72 and 127.11 (Ar),
60.40 (CH2O), 47.89 (CH), 38.41 (CH2), 14.08 (SCH3);
GC-MS (EI): m/z (relative intensity) 181 ([M2H]þ, 18),
134 (86), 117 (20), 105 (100), 91 (54), 77 (27), 45 (14).
Anal. calcd for C10H14OS: C, 65.89; H, 7.74. Found: C,
65.51; H, 7.88.
4.2. Syntheses of compounds 10, 12–18
4.2.1. 2-[(Methylthio)methyl]-N,N-dimethylbenzena-
mine (10). n-BuLi (1.91 M in methylcyclohexane, 75 mL,
143.3 mmol) was added to a solution of N,N-dimethyl-o-
toluidine (9) (14.5 mL, 99.6 mmol) in ether (50 mL). The
reaction mixture was refluxed for 8 h and subsequently
stirred at room temperature overnight. A solution of
dimethyl disulfide (13.2 mL, 148.5 mmol) in ether
(30 mL) was then added dropwise within 1 h with ice-
water bath cooling, and the mixture stirred at room
temperature overnight. Water was then added, the product
was extracted with ether, dried over Na2SO4, filtered and
evaporated to dryness. Purification was carried out by
distillation, yielding 10 (16.3 g, 90.1 mmol, 90%) as a
colourless oil, bp 69–708C (0.2 mbar). IR (neat): n 3065,
3020, 2978, 2935, 2920, 2863, 2830, 2785, 1598,
4.2.4. 2-[1-Methylthio-3-[(diphenylphosphino)oxy]pro-
pyl]-N,N-dimethyl-benzenamine (14). n-BuLi (1.80 M in
methylcyclohexane, 8 mL, 14.4 mmol) was added to a
solution of 12 (3.1 g, 13.8 mmol) in THF (30 mL) at 2788C.
The reaction mixture was stirred at room temperature
20 min and subsequently a solution of chlorodiphenyl-
phosphine (2.6 mL, 14.5 mmol) in THF (10 mL) was added
dropwise with ice-water cooling, and the mixture then
stirred at room temperature overnight. The volatile
materials were removed by evaporation, the residue was
suspended in toluene (100 mL) and filtered to remove the
inorganic salts. The solution was then passed through a short
column of neutral alumina. Evaporation of the solvent under
reduced pressure afforded 14 as a colourless oil (4.4 g,
10.8 mmol, 78%). IR (neat): n 3060, 3021, 2940, 2863,
2830, 2785, 1595, 1484, 1440, 1305, 1185, 1098, 1026, 950,
1
1490, 1454, 1305, 1155, 1045, 945, 760 cm21; H NMR
3
(CDCl3): d 7.42 (d, J¼7.4 Hz, 1H, Ar), 7.23–7.03 (m,
3H, Ar), 3.86 (s, 2H, CH2), 2.72 (s, 6H, N(CH3)2), 2.09
(s, 3H, SCH3); 13C{1H} NMR (CDCl3): d 152.98,
133.00, 130.42, 127.59, 123.40 and 119.64 (Ar), 45.21
(N(CH3)2), 33.50 (CH2), 15.61 (SCH3); GC-MS (EI):
m/z (relative intensity) 181 (Mþ, 45), 166 (20), 134
(100), 118 (39), 91 (24), 45 (13). Anal. calcd for
C10H15NS: C, 66.25; H, 8.34; N, 7.73. Found: C, 65.81;
H, 8.54; N, 7.88.
4.2.2. 2-[(1-Methylthio-3-hydroxy)propyl]-N,N-
dimethyl-benzenamine (12). n-BuLi (1.91 M in methyl-
cyclohexane, 32 mL, 61.1 mmol) was added dropwise over
30 min to a solution of 10 (9.1 g, 50.3 mmol) and TMEDA
(5 mL, 33.1 mmol) in methylcyclohexane (20 mL) with an
ice-salt cooling bath (temperature ,2108C), and stirred at
this temperature for an additional 1.5 h, yielding a pale
yellow suspension. Ether (50 mL) was then added. Ethylene
oxide (ca. 3 mL, 60 mmol) was condensed into a Schlenk
tube connected to the reaction flask via tubing and then
allowed to evaporate slowly (over 20 min) into the ice-salt
cooled reaction mixture which became slightly yellower.
After the addition was complete, the reaction mixture was
allowed to warm up slowly to room temperature and stirred
overnight. It was then poured into water and extracted with
dichloromethane. The organic extracts were washed with
water, dried over Na2SO4, filtered and evaporated to
dryness. Purification was carried out by distillation, yielding
12 (9.4 g, 41.8 mmol, 83%) as a colourless oil, bp 114–
1178C (0.2 mbar). IR (neat): n 3405, 3065, 3026, 2940,
2867, 2830, 2790, 1598, 1490, 1454, 1300, 1160, 1050, 945,
1
738, 695 cm21; H NMR (CDCl3): d 7.57–7.11 (m, 14H,
Ar), 4.76 (t, 3J¼7.6 Hz, 1H, CH), 4.05–3.88 (m, 2H,
CH2O), 2.64 (s, 6H, N(CH3)2), 2.39–2.22 (m, 2H, CH2),
1.97 (s, 3H, SCH3); 13C{1H} NMR (CDCl3): d 152.78–
2
120.04 (Ar), 67.86 (d, JP,C¼19.6 Hz, CH2OP), 45.56 (s,
3
N(CH3)2), 39.93 (s, CH), 37.80 (d, JP,C¼7.4 Hz, CH2),
14.38 (s, SCH3); 31P{1H} NMR (CDCl3): d 112.21 (s); ESI
MS: m/z 409 (Mþ). Anal. calcd for C24H28NOPS: C, 70.39;
H, 6.89; N, 3.42. Found: C, 70.63; H, 6.99; N, 3.06.
4.2.5. [1-Methylthio-3-[(diphenylphosphino)oxy]pro-
pyl]-benzene (15). Compound 15 was prepared from 13
(2.3 g, 12.6 mmol) by a similar procedure to that described
above for 14, in a yield of 70% (3.2 g, 8.7 mmol), as a
colourless oil. IR (neat): n 3060, 3025, 2945, 2920, 2872,
1
1594, 1487, 1440, 1228, 1026, 965, 738, 695 cm21; H
NMR (CDCl3): d 7.60–7.23 (m, 15H, Ar), 3.99–3.73 (m,
3H, CH and CH2O), 2.36–2.12 (m, 2H, CH2), 1.84 (s, 3H,
SCH3); 13C{1H} NMR (CDCl3): d 142.06–127.08 (Ar),
1
3
755 cm21; H NMR (CDCl3): d 7.55 (d, J¼7.5 Hz, 1H,
Ar), 7.24–7.11 (m, 3H, Ar), 4.60–4.54 (m, 1H, CH), 3.74
(br s, 1H, OH), 3.58–3.54 (m, 1H, CH2), 3.22–3.14 (m, 1H,
CH2), 2.70 (s, 6H, N(CH3)2), 2.32–2.24 (m, 1H, CH2), 2.02
(s, 3H, SCH3), 1.72–1.64 (m, 1H, CH2); 13C{1H} NMR
(CDCl3): d 152.08, 136.41, 128.19, 127.83, 125.38 and
119.11 (Ar), 59.66 (CH2O), 45.76 (N(CH3)2), 40.70 (CH),
40.07 (CH2), 14.84 (SCH3); GC-MS (EI): m/z (relative
intensity) 225 (Mþ, 5), 178 (100), 134 (49), 117 (20), 91
2
67.52 (d, JP,C¼19.5 Hz, CH2OP), 47.59 (s, CH), 37.55 (d,
3JP,C¼7.3 Hz, CH2), 14.24 (s, SCH3); 31P{1H} NMR
(CDCl3): d 112.69 (s). Anal. calcd for C22H23OPS: C,
72.11; H, 6.33. Found: C, 72.03; H, 6.25.
4.2.6. Palladium dichloro[2-[(1-methylthio-S)-3-[(di-
phenylphosphino-P)oxy]propyl]-N,N-dimethyl-benzena-
mine] (16). A solution of the ligand 14 (0.219 g, 0.53 mmol)

3472
I. D. Kostas et al. / Tetrahedron 59 (2003) 3467–3473
in dichloromethane (10 mL) was added dropwise to the dark
red solution of PdCl2(NCPh)2 (0.205 g, 0.53 mmol) in
dichloromethane (10 mL) with dry ice/acetone cooling. The
reaction mixture was warmed slowly to room temperature
and stirred overnight. The resulting yellow–orange solution
was evaporated under reduced pressure to a volume of
4 mL, and addition of ether (20 mL) caused the precipitation
of a solid. The solvents were decanted and the remaining
solid was washed with ether (2£20 mL) and dried, yielding
16 (0.296 g, 0.50 mmol, 95%) as a yellow solid, mp (dec.)
142–1458C. IR (neat): n 3055, 3020, 2948, 2865, 2830,
2790, 1592, 1485, 1436, 1310, 1187, 1105, 1030, 948, 795,
under argon with aryl bromide (1.0 mmol), styrene
(0.17 mL, 1.5 mmol), AcONa (0.164 g, 2.0 mmol), a stock
solution of complex 14 in DMF (1 or 0.01 mM, 1 mL, 0.001
or 0.00001 mmol, respectively) and decane (0.08 mL,
0.4 mmol) as internal standard, stirred in a preheated
1308C oil bath for 24 h, and then allowed to cool to room
temperature. After addition of aqueous NaOH and extrac-
tion with dichloromethane, the organic phase was washed
with brine, dried over Na2SO4, filtered, and analysed by GC
and GC-MS. After evaporation of the volatiles, the residue
was passed through a pad of silica gel with AcOEt/pentane
(5:1) as eluent, dried in vacuo and characterized by GC-MS,
1H and 13C NMR spectra. All the Heck products are known
compounds.2h,i,4h,j
1
695 cm21; H NMR (CD2Cl2): d 8.21–8.14 (m, 2H, Ar),
7.74–7.18 (m, 12H, Ar), 5.11 (br m), 4.78 (br m) and 4.46–
4.37 (m) (3£1H, CH and CH2), 2.45 (s, 6H, N(CH3)2),
2.56–2.30 (m, obscured with the singlet at 2.45 ppm, 2H,
CH2), 2.20 (s, 3H, SCH3); 13C{1H} NMR (CD2Cl2): d
153.31–121.37 (Ar), 67.96 (CH2OP), 46.01 (N(CH3)2),
44.95 (CH), 35.41 (CH2), 20.93 (SCH3); 31P{1H} NMR
(CD2Cl2): d 119.75 (br s); ESI MS: m/z 552 ([M2Cl]þ).
Anal. calcd for C24H28Cl2NOPPdS: C, 49.12; H, 4.81; N,
2.39. Found: C, 48.72; H, 4.72; N, 2.01.
4.4.2. General procedure for the Heck reaction catalysed
by in situ ligand and Pd(NCPh)2. Aryl bromide
(1.0 mmol), styrene (0.17 mL, 1.5 mmol), AcONa
(0.164 g, 2.0 mmol), a stock solution of ligand 14 or 15 in
DMF (2 or 0.02 mM, 0.5 mL, 0.001 or 0.00001 mmol,
respectively), PdCl2(PhCN)2 in DMF (2 or 0.02 mM,
0.5 mL, 0.001 or 0.00001 mmol, respectively) and decane
(0.08 mL, 0.4 mmol) as internal standard, stirred under
argon at room temperature for 10 min and then in a
preheated 1308C oil bath for 24 h, after which the reaction
mixture was allowed to cool to room temperature. The
workup procedure was as described above.
4.2.7. Mixture of dimeric palladium species 17 and 18.
Treatment of PdCl2(NCPh)2 (0.222 g, 0.58 mmol) in
dichloromethane (10 mL) with ligand 15 (0.212 g,
0.58 mmol) in dichloromethane (15 mL) as described
above for the synthesis of 16, yielded a mixture of the
isomeric complexes 17 and 18 as a yellow solid (0.273 g,
0.25 mmol, 86%), mp (dec.) 157–1708C. IR (neat): n 3060,
2970, 2925, 2885, 1590, 1485, 1440, 1105, 1020, 970, 748,
695 cm21; 1H NMR (CDCl3): d 8.58–6.88 (m, Ar), 4.50 (br
m), 4.20–4.07 (m), 3.65 (br m), 3.22 (br m), 2.89 (br m),
2.59 (br m), 2.29 (s, SCH3), 1.97 (s, SCH3) (ratio aromatic–
Acknowledgements
The investigation was supported by the Greek General
Secretariat of Research and Technology and the Russian
Foundation for Basic Research.
aliphatic protons¼15:8); 13C{1H} NMR (CDCl3):
d
2
131.09–127.69 (Ar), 65.90 (d, JP,C¼9.8 Hz) and 63.64
(s) (CH2OP), 54.55 (s) and 53.97 (s) (CH), 37.37 (s) and
36.37 (s) (CH2), 21.39 (s) and 15.24 (s) (SCH3); 31P{1H}
NMR (CDCl3): d 113.03 (s) and 111.12 (s). Anal. calcd for
C44H46Cl4O2P2Pd2S2: C, 48.59; H, 4.26. Found: C, 48.50;
H, 4.46.
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