Sulfination by using Pd-PEPPSI complexes: Studies into precatalyst activation, cationic and solvent effects and the role of butoxide base

Article abstract of DOI:10.1002/chem.201203142

The activation of PEPPSI precatalysts has been systematically studied in Pd-catalysed sulfination. Under the reactions conditions of the sulfide and KOtBu in toluene, the first thing that happens is exchange of the two chlorides on the PEPPSI precatalyst with the corresponding sulfides, creating the first resting state; it is via this complex that all Pd enters the catalytic cycle. However, it is also from this same complex that a tri-Pd complex forms, which is a more persistent resting state. Under standard reaction conditions, this complex is catalytically inactive. However, if additional pyridine or a smaller base (i.e., KOEt) is added, this complex is broken down, presumably initially back to the first resting state and it is again capable of entering the catalytic cycle and completing the sulfination. Of note, once the tri-Pd complex forms, one equivalent of Pd is lost to the transformation. Related to this, the nature of the cation of the sulfide salt and solvent dielectric is very important to the success of this transformation. That is, the less soluble the salt the better the performance, which can be attributed to lowering sulfide concentration to avoid the movement of the Pd-NHC complex into the above described off-cycle sulfinated resting states.

Full text of DOI:10.1002/chem.201203142

FULL PAPER
DOI: 10.1002/chem.201203142
Sulfination by Using Pd-PEPPSI Complexes: Studies into Precatalyst
Activation, Cationic and Solvent Effects and the Role of Butoxide Base**
Mahmoud Sayah,[a] Alan J. Lough,[b] and Michael G. Organ*[a]
Abstract: The activation of PEPPSI
precatalysts has been systematically
studied in Pd-catalysed sulfination.
Under the reactions conditions of the
sulfide and KOtBu in toluene, the first
thing that happens is exchange of the
two chlorides on the PEPPSI precata-
lyst with the corresponding sulfides,
creating the first resting state; it is via
this complex that all Pd enters the cat-
alytic cycle. However, it is also from
this same complex that a tri-Pd com-
plex forms, which is a more persistent
resting state. Under standard reaction
conditions, this complex is catalytically
inactive. However, if additional pyri-
dine or a smaller base (i.e., KOEt) is
added, this complex is broken down,
presumably initially back to the first
resting state and it is again capable of
entering the catalytic cycle and com-
pleting the sulfination. Of note, once
the tri-Pd complex forms, one equiva-
lent of Pd is lost to the transformation.
Related to this, the nature of the cation
of the sulfide salt and solvent dielectric
is very important to the success of this
transformation. That is, the less soluble
the salt the better the performance,
which can be attributed to lowering
sulfide concentration to avoid the
movement of the Pd-NHC complex
into the above described off-cycle sulfi-
nated resting states.
Keywords: homogeneous catalysis ·
palladium · PEPPSI · sulfination
Introduction
The presence of aryl– and alkyl–sulfur motifs in the struc-
ture of natural products, therapeutics and drug candidates
À
makes the formation of C S linkages an important pursuit
in synthetic chemistry.[1] Unfortunately, many of the meth-
ods that have been developed to introduce sulfur into target
molecules involve rather harsh conditions, which is especial-
ly true for aryl sulfides.[2] Catalysis offers the promise of
much gentler reaction conditions although late transition
metals, such as Pd, can be poisoned by the relatively soft
sulfur centre. That said, there have been significant develop-
ments in sulfination by using Pd catalysts with phosphane li-
gands.[3]
Figure 1. Putative catalytic cycle for Pd-catalysed sulfination.
The sulfination catalytic cycle (Figure 1) has been thor-
oughly investigated by Hartwig and co-workers, who have
postulated a number of off-cycle resting states (e.g., 3, 6).[4]
To add to these challenges, if reduction [H] of the precata-
lyst (1) is slow, additional deleterious side reactions with Pd
can occur, further compromising catalysis. Unlike the situa-
tion with nucleophilic organometallics in cross coupling, or
alkyl amines in amination chemistry, the mechanism by
which PdII is reduced to Pd0 is less clear with aryl sulfides.
With phosphane ligands, Hartwig proposed that, although
energetically disfavoured, reductive elimination (RE) of
diaryl disulfide from 3 was the most plausible pathway for
Pd0 (2) to be introduced to the catalytic cycle, given rate
studies in their investigation.[4] The authors were not able to
confirm the existence of the disulfide in their reactions and
attributed this to its consumption given the reductive condi-
tions of the coupling.
[a] M. Sayah, Prof. M. G. Organ
Department of Chemistry, York University
4700 Keele Street, Toronto, Ontario M3J 1P3 (Canada)
Fax : (+1)416-736-5936
E-mail: organ@yorku.ca
[b] Dr. A. J. Lough
Department of Chemistry
University of Toronto 80 St. George Street
Toronto, Ontario M5S 3H6 (Canada)
Results and Discussion
[**] PEPPSI=Pyridine-enhanced precatalyst preparation stabilisation and
initiation.
Recently we reported that N-heterocyclic carbene (NHC)-
based Pd-PEPPSI-IPent (PEPPSI=pyridine-enhanced pre-
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201203142.
Chem. Eur. J. 2013, 00, 0 – 0
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
1
&
ÞÞ
These are not the final page numbers!

catalyst preparation stabilisation and initiation; IPent=1,3-
bis(2,6-diisopentylphenyl)imidazol-2-ylidene) was highly ef-
fective for sulfinating strongly deactivated substrates at
room temperature, although precatalyst activation with
Bu2Mg, morpholine or isopropoxide was necessary.[5] Preca-
talyst activation appeared not to be necessary with phos-
phane ligands and encouraged us to look deeper at the elec-
tronic and steric parameters of the ligands on Pd. We inves-
tigated the challenging coupling of thiophenol (10) to the
hindered oxidative addition partner 9 (Scheme 1). Beginning
our study with the IPr NHC core (IPr=1,3-bis(2,6-diisopro-
pylphenyl)imidazol-2-ylidene), we found that heating to
808C with KOtBu was sufficient to activate Pd-PEPPSI-IPr
(12) and drive catalysis without additional additives. When
the 3-chloropyridine-based PEPPSI precatalyst system was
designed, we expected that the electronegative chlorine
would assist in dissociating the pyridine moiety.[6] When we
performed the coupling with the simple pyridine derivative
13, we were surprised to find it was consistently activated at
a temperature 108C lower than catalyst 12.[7] Interestingly,
introducing a substituent at the 4-position of the pyridyl
moiety (14–17), even an electron-withdrawing one (e.g., 17)
completely suppressed precatalyst activation. In another in-
teresting twist, introduction of substituents at the 2-position,
even an electron-donating one (18),showed good reactivity,
although, adding an additional substituent to the 4-position
(19) proved detrimental. When both ortho positions were
occupied by methyl groups, the activation temperature drop-
ped by an additional 108C (20). Presuming that precatalyst
activation is preceded by exchange of the two chlorides to
sulfides (vide infra), the increased bulk can be viewed to
have two divergent effects.[8] Bulk at the ortho position
could slow ligand exchange to the larger sulfide that could
impact activation overall, but this was not observed. Con-
versely, the increased bulk could drive disulfide RE and pro-
mote precatalyst activation. Electronically, the placement of
substituents, even electron-donating ones, appear to reduce
bond order between the palladium and nitrogen atoms be-
cause the bulk of the substituent elongates this coordinate
bond, rendering the metal more electrophilic, and thus pos-
sibly more likely to undergo reduction (see Table 1 and
À
À
À
Table 1. Effect of ligated pyridine motif on Pd S, Pd N and Pd C bond
lengths of resting states 28 and 29 derived from precatalysts 13 and 20,
respectively. For ORTEP representation of crystal structures 28 and 29
see Figure 2.
À
À
À
Pd S bond [ꢁ]
Pd N bond [ꢁ]
Pd C bond [ꢁ]
28
29
2.333
2.347
2.077
2.096
1.978
1.985
Figure 2 for crystal structures of key disulfide resting
states).[8] Similarly, the Pd S bond length is longer with
À
ortho-substituted pyridine complexes, also facilitating RE of
disulfide. With these thoughts in mind we made two addi-
tional modifications to the IPr scaffold. Further increasing
the bulk at the ortho-positions from methyl to ethyl (21)
shut down catalyst activation entirely. Conversely, placement
of chlorine atoms on the NHC backbone (22) lowered the
activation temperature by an additional ten degrees to
508C. It is tempting to suggest that this additional boost in
reactivity is solely due to electronic factors, but the chlorine
atoms also push the N-aryl groups inward toward Pd, mean-
ing that they could have a steric role, despite the distance
from the Pd centre.[9]
Given that Pd-PEPPSI-IPent was found to be much more
reactive than the IPr derivatives in previously reported cou-
pling reactions,[5,10] we shifted attention to modifications of
the IPent platform. While the simple pyridine derivative
(23) did not show greatly improved activation relative to 13,
the mono-ortho-methyl derivative (25) reduced the activa-
tion temperature to 508C. In addition to the increased size
of the N-phenyl substituent itself, further increasing the
Scheme 1. Sulfination of 2-bromo-1,3-dimethylbenzene (9) with thiophe-
nol (10) using a variety of Pd-PEPPSI complexes without activators at
different temperatures.
&
2
&
www.chemeurj.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Sulfination by Using Pd-PEPPSI Complexes
FULL PAPER
Scheme 2. Pd complexes formed from interactions with phenylsulfide.
ORTEP representation of the crystal structure of 30 (ellipsoids drawn at
the 30% level).[8]
to the disulfide (e.g., 28) and it is this species that undergoes
reduction and enters the main catalytic cycle.
When the reaction mixture containing stoichiometric pre-
catalyst 13 from the NMR experiment was left to stand, two
visibly different crystals formed. Careful separation of these
crystals, followed by X-ray analysis confirmed the structures
of revealed complex 28 (Figure 2) and tripalladium complex
30, which we could then identify and track by 1H NMR
spectroscopy.[13] This interesting tripalladium species, which
has lost one NHC, has no catalytic activity as these crystals
failed to produce any sulfinated product under the reaction
conditions (Scheme 2b, ii). However, when additional pyri-
dine or KOEt (Scheme 2b, iii and iv) was added to the reac-
Figure 2. ORTEP representation of crystal structures 28 (top) and 29
(bottom) with ellipsoids drawn at the 30% level; hydrogen atoms omit-
ted for clarity.
bulk on the pyridine (26) rendered the complex less active.
Finally, as was observed with the IPr platform, chlorinating
the NHC backbone led to optimal precatalyst 27[11] that
could be smoothly activated at 408C without the aid of any
additive to promote PdII reduction.
In order to gain additional insight into the mechanism of
activation, we followed the reaction with stoichimetric pre-
catalyst 13 by 1H NMR spectroscopy (Scheme 2a).[12] By
keeping the temperature below that which is necessary for
reduction (i.e., RT), we could follow the rapid conversion of
13 to disulfide 28. We then took 28, which is stable and can
be purified by column chromatography, and subjected it to
the reaction conditions from Scheme 1 and near quantitative
sulfination was observed. These experiments confirm that
the dichloro precatalysts first undergo rapid ligand exchange
tion, 30 was broken down liberating NHC–PdACTHNURGTNEUNG(SPh)2, pre-
sumably, which then completes the reaction.
While diphenyldisulfide is suggested to be susceptible to
reduction under sulfination conditions,[4] its presence, how-
ever brief, could shift the equilibrium back to the more
stable PdII complex (e.g., Figure 1). To examine this, preca-
talyst 13 was reduced with one equivalent of dibutylmagne-
sium, immediately followed by addition of ditolyldisulfide
[TolSSTol; all at 08C, Eq. (1)]. The sequence was monitored
Chem. Eur. J. 2013, 00, 0 – 0
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
3
&
ÞÞ
These are not the final page numbers!

M. G. Organ et al.
by 1H NMR spectroscopy and in the end 32 was isolated
(60%).[12] Conversely, when 32 by itself was heated to
1008C no disulfide was observed, although approximately
half of it underwent RE of the carbene to produce 34. To
confirm that Pd0 is formed from 32 under our sulfination
conditions, 33 was added to the reaction to trap the active
catalyst (31) as complex 35. In the absence of base, the start-
ing materials were recovered. However, when KOtBu was
used, intermediate 35 was observed with 34 accounting for
the mass balance. When lithium isopropoxide was added in
addition to KOtBu to ensure complete reduction of 32,
quantitative conversion to 35 was observed. So, in the sulfi-
nation process precatalyst 13 gives rise to 32 in situ that re-
ductively eliminates disulfide to produce the active NHC–
Pd0 complex 31, which then enters the catalytic cycle.
other solvents. In every case in which the potassium thiolate
was soluble (Table 2, entries 5–8), sulfination failed to pro-
ceed at all. To ensure that this was not a consequence of the
precatalyst failing to activate, the reaction in DMSO was
pre-activated with Bu2Mg and only trace product was ob-
served (entry 6). Furthermore, we know that our standard
sulfination conditions in DMSO reduce 32 as we were able
to isolate 35 as shown in Equation (2).
Key to the success of sulfination is the presence of butox-
ide base. Reduction of the dithiane by butoxide introduces
more active catalyst into the catalytic cycle and helps to pre-
vent movement of the equilibrium back toward 32. Activa-
tion of resting state 30 does not occur thermally (Scheme 2b,
ii), only when either pyridine or KOEt (Scheme 2b, iii and
iv) was added, suggesting that butoxide is too hindered to
When the sulfination reactions carried out in this study
proceeded well, the physical appearance of the mixture
throughout the course of the reaction followed a pattern.
Potassium thiolate is insoluble in toluene, leading to a
highly heterogeneous mixture that was a challenge to stir at
the beginning, but gradually became fully homogeneous as
the reaction progressed. The choice of cation is known to be
important in amination reactions, so we evaluated different
thiolate salts. The sodium salt, which was similarly insoluble,
failed to provide any sulfinated product at 708C, but when
heated to 908C led to 40% conversion (Table 2, entry 2).
Conversely, the lithium salt failed to form any product
(entry 3), but unlike the potassium or sodium thiolates, was
fully soluble. As solubility may play a key role, we examined
break down 30, which liberates NHC–PdACTHNUTRGENUG(N SPh)2. Nonethe-
less, when Bu2Mg-activated 13 was reacted with pre-formed
potassium thiolate, the reaction was sluggish [Eq. (3) path
ii]. However, when a catalytic amount of butoxide was
added, the reaction proceeded quantitatively [Eq. (3) pa-
th iii]. With KSPh already in the flask, this clearly points to
an additional role for butoxide, which we attribute to cata-
lyst activation and the continuous reduction of any dithiane
that forms.
Table 2. Effect of cation and solvent on sulfination using precatalyst 13.
Conclusion
Solvent
Cation [M]
Appearance
Result
In this report we have systematically designed a series of
highly active NHC-based precatalysts specific for sulfina-
tion. In amination studies, 12 activates spontaneously at
room temperature and couples aniline nucleophiles with
high efficiency under identical reaction conditions (toluene,
KOtBu)[10a] verifying the unique off-cycle poisoning that
faces sulfination. Soluble thiolate salts in toluene, such as
LiSAr, or the use of high dielectric solvents such as N-
methyl-2-pyrrolidone (NMP) or DMSO, suppresses the
transformation. We believe that the low solubility and there-
fore, the low concentration of the thiolate ion in solvents
such as toluene, is essential for good reactivity.
1
2
3
4
5
6
7
8
toluene
toluene
toluene
THF
DMSO
DMSO
NMP[d]
isopropanol
K
heterogeneous
heterogeneous
fully soluble
heterogeneous
fully soluble
fully soluble
fully soluble
fully soluble
100% conv.
NR[a]
Na
Li
K
K
K
NR
35% conv.[b]
NR
NR[c]
NR
trace
K
K
[a] Reaction did not proceed at 708C, but did proceed to 40% conversion
when heated to 908C. [b] When the reaction was run for 48 h, 60% con-
version was observed. [c] When catalyst 13 was pre-activated with Bu2Mg
the reaction proceeded to 15% conversion. Again, the mixture was fully
homogeneous.
&
4
&
www.chemeurj.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Sulfination by Using Pd-PEPPSI Complexes
FULL PAPER
12H), 1.14 ppm (d, J=6.9 Hz, 12H); 13C NMR (100 MHz, CDCl3): d=
155.2, 150.6, 149.1, 146.5, 135.0, 130.1, 127.9, 127.7, 127.5, 124.8, 124.7,
123.9, 28.6, 26.2, 23.1, 20.8 ppm; HRMS (ES): m/z calcd for
C66H86Cl4N6NaPd2 [2M<M+ >Na]+: 1332.4081; found: 1332.4056.
Experimental Section
General coupling procedure: In a glovebox, an oven-dried vial (4 mL
screw-cap threaded) equipped with magnetic stir bar was charged with
Pd-PEPPSI catalyst (2 mol%) and KOtBu (60 mg, 2 equiv, 0.5 mmol).
The vial was sealed with a Teflonꢂ-lined screw cap, removed from the
glovebox and 9 (1 equiv, 0.25 mmol) was added by microliter syringe fol-
lowed by toluene (2 mL). Compound 10 (1.2 equiv, 0.3 mmol) was added
dropwise and the reaction was stirred at the indicated temperature for
24 h. At this point the reaction was cooled to room temperature and un-
decane (25 mL) was added. Thereafter a 20 mL aliquot were filtered
through a plug of silica gel and eluted with EtOAc into a GC vial for
GC-MS analysis.
Synthesis of complex 15: Following
the general procedure with para-me-
thoxypyridine (9.6 mg, 0.088 mmol),
the reaction was stirred at room tem-
perature for 1 h providing 15 (57.5 mg,
97%) as a pale-yellow powder. M.p.
2158C (decomp); 1H NMR (300 MHz,
CDCl3): d=8.38 (d, J=6.4 Hz, 2H),
7.51 (t, J=7.6 Hz, 2H), 7.36 (d, J=
7.6 Hz, 4H), 7.13 (s, 2H), 6.60 (d, J=6.4 Hz, 2H), 3.75 (s, 3H), 3.20
(sept, J=6.8 Hz, 4H), 1.50 (d, J=6.8 Hz, 12H), 1.13 ppm (d, J=6.8 Hz,
12H); 13C NMR (100 MHz, CDCl3): d=166.3, 155.3, 152.3, 146.6, 135.1,
130.2, 124.9, 124.0, 109.9, 55.5, 28.7, 26.3, 23.2 ppm; HRMS (EI): m/z
calcd for C33H43ClN3OPd [MÀCl]+: 638.2129; found: 638.2131.
(2,6-Dimethylphenyl)ACTHNUGTRNEUNG(phenyl)sulfane
(11): Following the general procedure,
the reaction was conducted using Pd-
PEPPSI precatalyst 27 (4.8 mg,
2 mol%) at 408C for 24 h. After chro-
matography (pentane, Rf =0.3)(2,6-
Synthesis of complex 16: Following
the general procedure with para-N,N-
dimethylphenyl)ACHTUNGTRENNUNG(phenyl)sulfane (53 mg, 99%) was obtained as a pale-
dimethylypyridine
(10.8 mg,
yellow oil. 1H NMR (300 MHz, CDCl3): d=7.30–7.19 (m, 5H), 7.10 (t,
J=7.2 Hz, 1H), 6.97 (d, J=7.2 Hz, 2H), 2.47 ppm (s, 6H). Spectral data
were in accordance with those reported in the literature.[14]
0.088 mmol), the reaction was stirred
at room temperature for 1 h providing
16 (58 mg, 97%) as a yellow powder.
M.p. 2858C (decomp); 1H NMR
General procedure for the synthesis of complexes 12–21 starting from the
chloro-bridged NHC-IPr Dimer: An oven-dried vial (4 mL screw-cap
(300 MHz, CDCl3): d=8.07 (d, J=
6.6 Hz, 2H), 7.49 (t, J=7.5 Hz, 2H),
7.35 (d, J=7.5 Hz, 4H), 7.11 (s, 2H), 6.22 (d, J=6.6 Hz, 2H), 3.22 (sept,
J=6.8 Hz, 4H), 2.89 (s, 3H), 1.50 (d, J=6.8 Hz, 12H), 1.13 ppm (d, J=
6.8 Hz, 12H); 13C NMR (100 MHz, CDCl3): d=156.8, 154.2, 150.1, 146.6,
135.2, 129.9, 124.7, 123.9, 106.2, 38.9, 28.6, 26.2, 23.2 ppm; HRMS (EI):
m/z calcd for C34H46ClN4Pd [MÀCl]+: 651.2446; found: 651.2437.
Synthesis of complex 17: Following the
general procedure with para-trifluoro-
methylpyridine (13 mg, 0.088 mmol),
the reaction was stirred at room tem-
perature for 16 h providing 17 (62 mg,
threaded) equipped with magnetic stir bar was charged with the dimer
(50 mg, 0.044 mmol). The vial was sealed with a Teflonꢂ-lined screw cap
and the indicated pyridine derivative (2 equiv) was added by syringe
under argon followed by CH2Cl2 (1 mL). The solution was stirred at the
indicated temperature and time, whereupon it was filtered through a
small plug of silica and eluted with CH2Cl2 (4 mL). Solvent was removed
under reduced pressure to afford pure product in all cases.
99%) as
>3008C
a
yellow powder. M.p.
(decomp);
1H NMR
(400 MHz, CD2Cl2): d=8.90 (d, J=
5.6 Hz, 2H), 7.56 (t, J=7.6 Hz, 2H),
7.46–7.40 (m, 6H), 7.22 (s, 2H), 3.18 (sept, J=6.4 Hz, 4H), 1.48 (d, J=
6.4 Hz, 12H), 1.15 ppm (d, J=6.4 Hz, 12H); 13C NMR (75 MHz, CDCl3):
d=153.2, 152.6, 146.6, 139.3 (q, J=34.5 Hz), 134.9, 130.3, 125.1, 124.0,
119.9, 119.8, 28.7, 26.3, 23.2 ppm; HRMS (EI): m/z calcd for
C33H40ClF3N3Pd [MÀCl]+: 676.1897; found: 676.1917.
Synthesis of complex 12: Following
the general procedure with meta-chlor-
opyridine (10 mg, 0.088 mmol), the re-
action was stirred at room tempera-
ture for 1 h providing 12 (57 mg, 95%)
Synthesis of complex 18: Following
the general procedure with ortho-
methylpyridine (8.2 mg, 0.088 mmol),
the reaction was stirred at room tem-
perature for 1 h providing 18 (56 mg,
97%) as a yellow powder. M.p. 1958C
as
a yellow powder. Spectral data
were in accordance with those report-
ed in the literature.[7]
Synthesis of complex 13: Following
the general procedure with pyridine
(7 mg, 0.088 mmol), the reaction was
stirred at room temperature for 1 h
providing 13 (57 mg, 98%) as a yellow
powder. Spectral data were in accord-
ance with those reported in the litera-
ture.[7]
(decomp);
1H NMR
(400 MHz,
CDCl3): d=8.24 (brs, 1H), 7.55 (brs,
2H), 7.41 (brs, 5H), 7.17 (brs, 2H),
6.96 (brs, 2H), 3.19 (brs, 4H), 2.57 (s, 3H), 1.48 (brs, 12H), 1.13 ppm
(brs, 12H); 13C NMR (100 MHz, CDCl3): d=159.2, 157.1, 150.2, 146.9,
136.8, 135.2, 135.1, 135.0, 130.1, 125.2, 124.8, 123.7, 121.4, 28.7, 26.3, 24,9,
23.1, 22.6 ppm; HRMS (ES): m/z calcd for C33H44Cl2N3Pd [M+H]+:
660.1943; found: 660.1923.
Synthesis of complex 14: Following
the general procedure with para-meth-
ylpyridine (8.2 mg, 0.088 mmol), the
reaction was stirred at room tempera-
ture for 1 h providing 14 (57 mg, 98%)
Synthesis of complex 19: Following
the general procedure with 2,4-dime-
thylpyridine (9.5 mg, 0.088 mmol), the
reaction was stirred at room tempera-
ture for 1 h providing 19 (57 mg, 96%)
as
a
yellow powder. M.p. >3008C
(decomp);
1H NMR
(300 MHz,
CDCl3): d=8.39 (d, J=4.8 Hz, 2H),
7.51 (t, J=7.8 Hz, 2H), 7.37 (d, J=7.8 Hz, 4H), 7.14 (s, 2H), 6.91 (d, J=
4.8 Hz, 2H), 3.19 (sept, J=6.9 Hz, 4H), 2.23 (s, 3H), 1.50 (d, J=6.9 Hz,
as
(decomp);
CDCl3): d=8.06 (brs, 1H), 7.54 (brs,
a
yellow powder. M.p. 2248C
1H NMR
(300 MHz,
Chem. Eur. J. 2013, 00, 0 – 0
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
5
&
ÞÞ
These are not the final page numbers!

M. G. Organ et al.
2H), 7.41 (brs, 4H), 7.16 (brs, 2H), 6.81 (brs, 2H), 3.19 (brs, 4H), 2.51
(brs, 3H), 2.16 (brs, 3H), 1.48 (brs, 12H), 1.13 ppm (brs, 12H);
13C NMR (75 MHz, CDCl3): d=158.6, 157.6, 157.4, 156.2, 150.2, 149.7,
148.5, 147.8, 146.9, 137.8, 135.3, 135.2, 135.1, 135.0, 131.1, 130.1, 126.1,
124.8, 123.8, 122.6, 121.7, 28.7, 26.4, 24.7, 24.4, 23.2, 22.9, 22.7, 22.6, 20.7,
17.9 ppm; HRMS (ES): m/z calcd for C34H46Cl2N3Pd [M+H]+: 672.2104;
found: 672.2111.
Synthesis of complex 24: Following
the general procedure, the reaction
was conducted using IPent·HCl
(54 mg, 0.1 mmol) and para-methylpyr-
idine providing 24 (64 mg, 83%) as a
yellow powder following column chro-
matography (pentane/CH2Cl2 5:1, Rf =
0.31). M.p. 1918C (decomp); 1H NMR
(300 MHz, CDCl3): d=8.42 (d, J=
5.7 Hz, 2H), 7.45 (t, J=7.5 Hz, 2H), 7.25 (d, J=7.5 Hz, 4H), 7.07 (s,
2H), 6.90 (d, J=5.7 Hz, 2H), 2.83 (m, 4H), 2.23 (s, 3H), 2.14 (m, 4H),
1.87 (m, 4H), 1.55 (m, 8H), 1.12 (t, J=7.2 Hz, 12H), 0.79 ppm (t,
J=7.2 Hz, 12H); 13C NMR (75 MHz, CDCl3): d=154.1, 150.7, 148.9,
144.6, 136.7, 129.0, 125.2, 124.7, 41.1, 28.7, 27.1, 20.8, 12.9, 11.1 ppm;
HRMS (ES): m/z calcd. for C41H60Cl2N3Pd [M+H]+: 770.3199; found:
770.3246.
Synthesis of complex 20: Following
the general procedure with 2,6-dime-
thylpyridine (9.5 mg, 0.088 mmol), the
reaction was stirred at room tempera-
ture for 4 h providing 20 (59 mg, 99%)
as
a yellow powder. Spectral data
were in accordance with those report-
ed in the literature.[7]
Synthesis of complex 21: Following the
general procedure with 2,6-diethypyri-
dine (12 mg, 0.088 mmol), the reaction
Synthesis of complex 25: Following
the general procedure, the reaction
was conducted using IPent·HCl
(54 mg, 0.1 mmol) ortho-methylpyri-
dine providing 25 (61 mg, 79%) as a
yellow powder following column chro-
was stirred at 408C for 16 h providing
21 (59 mg, 95%) as a yellow powder.
M.p. >3008C (decomp); 1H NMR
(300 MHz, CDCl3): d=7.58 (t, J=
matography (pentane/CH2Cl2 4:1, Rf =
8.1 Hz, 2H), 7.45–7.37 (m, 5H), 7.20 (s, 2H), 6.82 (d, J=7.8 Hz, 2H),
3.31–3.17 (m, 8H), 1.43 (d, J=7.2 Hz, 12H), 1.11 (d, J=7.2 Hz, 12H),
1.02 ppm (t, J=7.5 Hz, 6H); 13C NMR (75 MHz, CDCl3): d=163.5,
158.2, 147.4, 137.5, 135.1, 130.0, 124.8, 123.6, 120.1, 31.3, 28.8, 26.6, 22.5,
12.5 ppm; HRMS (ES): m/z calcd for C36H50Cl2N3Pd [M+H]+: 700.2417;
found: 700.2434.
0.30). M.p. 2508C (decomp); 1H NMR
(300 MHz, CDCl3): d=8.25 (d, J=5.1 Hz, 1H), 7.49 (t, J=7.8 Hz, 2H),
7.39 (t, J=8.1 Hz, 1H), 7.29 (d, J=7.8, 4H), 7.12 (s, 2H), 6.98–6.90 (m,
2H), 2.85 (m, 4H), 2.57 (s, 3H), 2.10 (m, 4H), 1.85 (m, 4H), 1.52 (m,
8H), 1.07 (t, J=7.2 Hz, 12H), 0.78 ppm (t, J=7.2 Hz, 12H); 13C NMR
(100 MHz, CDCl3): d=159.4, 156.4, 150.4, 145.0, 136.9, 136.7, 136.2,
128.7, 125.2, 124.9, 121.2, 40.5, 27.9, 27.8, 26.2, 25.1, 12.5, 10.4 ppm;
HRMS (ES): m/z calcd for C41H60Cl2N3Pd [M+H]+: 770.3199; found:
770.3228.
General procedure for the synthesis of complexes 22–27: An oven-dried
vial (4 mL screw-cap threaded) equipped with magnetic stir bar was
charged with the indicated imidazolium chloride salt (1 equiv, 0.1 mmol),
Cs2CO3 (5 equiv, 164 mg, 0.5 mmol) and pyridine derivative (1 mL) that
served as the solvent. The vial was sealed with a Teflonꢂ-lined screw cap,
and the reaction was stirred at 908C for 24 h. At that time the mixture
was filtered through a small plug of silica (eluted with CH2Cl2 (5 mL)).
The filtrate was concentrated to 0.5 mL under reduced pressure and
loaded onto a silica column and flashed using the indicated eluent
system.
Synthesis of complex 26: Following
the general procedure, the reaction
was conducted using IPent·HCl
(54 mg, 0.1 mmol) and 2,6-dimethyl-
methylpyridine providing 26 (68 mg,
87%) as a yellow powder following
column chromatography (pentane/
CH2Cl2 6:1, Rf =0.35). M.p. 2988C
Synthesis of complex 22: Following
1
the general procedure, the reaction
(decomp); H NMR (300 MHz, CDCl3): d=7.47 (t, J=7.8 Hz, 2H), 7.33–
was
conducted
using
IPrCl·HCl
7.23 (m, 5H), 7.18 (s, 2H), 6.75 (d, J=7.5 Hz, 2H), 2.82 (m, 4H), 2.58 (s,
6H), 2.05 (m, 4H), 1.84 (m, 4H), 1.53 (m, 8H), 1.06 (t, J=7.2 Hz, 12H),
0.78 ppm (t, J=7.2 Hz, 12H); 13C NMR (75 MHz, CDCl3): d=158.9,
158.3, 145.5, 137.2, 135.7, 128.6, 125.3, 124.8, 122.1, 40.2, 27.2, 25.6, 25.0,
12.3, 9.9 ppm; HRMS (ES) m/z calcd for C42H62Cl2N3Pd [M+H]+:
784.3356; found: 784.3388.
(49.5 mg, 0.1 mmol) and 2,6-dimethyl-
pyridine providing 22 (31 mg, 41%) as
a
yellow powder following column
chromatography (pentane/CH2Cl2 1:1,
Rf =0.2). M.p. 2158C (decomp);
1H NMR (400 MHz, CDCl3): d=7.61 (d, J=7.6 Hz, 2H), 7.45 (t, J=
7.6 Hz, 4H), 7.30 (t, J=7.6 Hz, 1H), 7.78 (d, J=7.6 Hz, 2H), 3.07 (sept,
J=6.4 Hz, 4H), 2.57 (s, 6H), 1.46 (d, J=6.4 Hz, 12H), 1.20 ppm (d, J=
6.4 Hz, 12H); 13C NMR (75 MHz, CDCl3): d=162.6, 158.8, 148.1, 137.5,
132.2, 130.9, 124.4, 122.3, 120.2, 28.9, 25.5, 24.9, 24.3 ppm; HRMS (EI):
m/z calcd for C34H43Cl3N3Pd [MÀCl]+: 704.1557; found: 704.1543.
Synthesis of complex 27: Following the
general procedure, the reaction was
conducted using IPentCl·HCl (60.6 mg,
0.1 mmol) and ortho-methylpyridine
providing 27 (50 mg, 59%) as a yellow
powder following column chromatog-
raphy (pentane/CH2Cl2 2:1, Rf =0.25).
Synthesis of complex 23: Following
the general procedure, the reaction
M.p. 1858C (decomp); 1H NMR
(400 MHz, CDCl3): d=8.21 (d, J=
was conducted using IPent·HCl
6.0 Hz, 1H), 7.54 (t, J=7.6 Hz, 2H), 7.41 (t, J=7.2 Hz, 1H), 7.35 (d, J=
7.6, 4H), 6.99–6.93 (m, 2H), 2.97 (brs, 4H), 2.52 (s, 3H), 2.01–1.85 (m,
8H), 1.73–1.64 (m, 4H), 1.54–1.45 (m, 4H), 1.08 (t, J=7.2 Hz, 12H),
0.82 ppm (t, J=7.2 Hz, 12H); 13C NMR (100 MHz, CDCl3): d=159.8,
159.3, 150.3, 145.6, 136.9, 133.1, 129.4, 126.3, 125.4, 121.4, 120.7, 40.3,
26.9, 25.8, 24.9, 12.3, 10.3 ppm; HRMS (ES): m/z calcd for C41H58Cl4N3Pd
[M+H]+: 838.242; found: 838.2454.
(54 mg, 0.1 mmol) and pyridine pro-
viding 23 (60.6 mg, 80%) as a yellow
powder following column chromatog-
raphy (pentane/CH2Cl2 5:1, Rf =0.31).
M.p. 1618C (decomp); 1H NMR
(300 MHz, CDCl3): d=8.59 (d, J=
5.4 Hz, 2H), 7.54 (t, J=7.8 Hz, 1H), 7.46 (t, J=7.5 Hz, 2H), 7.24 (brs,
4H), 7.12–7.07 (m, 4H), 2.84 (m, 4H), 2.17 (m, 4H), 1.88 (m, 4H), 1.58
(sept, J=7.2 Hz, 8H), 1.15 (t, J=7.2 Hz, 12H), 0.84 ppm (t, J=7.2 Hz,
12H); 13C NMR (75 MHz, CDCl3): d=153.6, 151.4, 144.6, 137.2, 136.7,
129.0, 125.2, 123.9, 41.1, 28.7, 27.1, 12.9, 11.1 ppm; HRMS (ES): m/z
calcd for C40H58Cl2N3Pd [M+H]+: 756.3043; found: 756.3057.
General procedure for the synthesis of complexes 28, 29, 30 and 32: In
the glovebox, an oven-dried vial (4 mL screw-cap threaded) equipped
with magnetic stir bar was charged with the corresponding Pd-PEPPSI
complex (1 equiv, 0.15 mmol) and KOtBu (55 mg, 3.1 equiv, 0.465 mmol).
The vial was sealed with a Teflonꢂ-lined screw cap and removed from the
&
6
&
www.chemeurj.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Sulfination by Using Pd-PEPPSI Complexes
FULL PAPER
glovebox whereupon the corresponding thiol (3 equiv, 0.45 mmol) was
added followed by toluene (2 mL). The reaction mixture was stirred at
the indicated temperature and time after which the reaction vial was cen-
trifuged and the supernatant transferred to a round bottom flask. The re-
maining solid was washed with toluene (3ꢃ1 mL), centrifuging each
time, and the combined supernatant was evaporated under reduced pres-
sure and the residue purified as indicated.
ties from pentane and leaving 31 in
the mother liquor as a clean product.
Solvent removal provided 32 (113 mg,
80%) as a yellow powder. M.p. 88–
908C; 1H NMR (400 MHz, C6D6): d=
8.83 (d, J=4.0 Hz, 2H), 7.45 (t, J=
8.0 Hz, 2H), 7.39 d, J=8.0 Hz, 4H),
6.86–6.83 (m, 6H), 6.50 (d, J=8.0 Hz, 4H), 6.25 (t, J=4.0 Hz, 1H), 6.02
(t, J=4.0 Hz, 2H), 3.6 (sept, J=8.0 Hz, 4H), 2.0 (s, 6H), 1.85 (d, J=
8.0 Hz, 12H), 1.26 ppm (d, J=8.0 Hz, 12H); 13C NMR (75 MHz, C6D6):
d=169.7, 151.6, 146.8, 143.6, 136.7, 134.8, 132.4, 129.8, 129.6, 124.7, 124.0,
122.1, 29.2, 26.4, 23.2, 20.5 ppm; HRMS (EI): m/z calcd for C46H56N3S2Pd
[M+H]+: 820.2950; found: 820.2957.
Synthesis of complex 28: Following
the general procedure 13 (97 mg,
0.15 mmol)
and
10
(3 equiv,
0.45 mmol) were reacted at room tem-
perature for 2 h. The supernatant ob-
tained from the centrifugation process
Preparation of compound 34 from 32:
An oven-dried vial (4 mL screw-cap
threaded) equipped with a magnetic
stir bar was charged with complex 31
(30 mg, 0.031 mmol) followed by
[D6]benzene. The vial was sealed with
was evaporated and the product was
purified by crystallising 29 out of solu-
tion using pentane/CH2Cl2 at À208C, which left 28 in the mother liquor
as a clean product. Solvent removal provided 28 (82 mg, 60%) as a red
powder. M.p. 82–848C; 1H NMR (400 MHz, CDCl3): d=8.35 (d, J=
4.8 Hz, 2H), 7.43 (t, J=8.0 Hz, 2H), 7.30 (d, J=8.0 Hz, 4H), 7.23 (s,
2H), 7.0 (t, J=8.0 Hz, 1H), 6.50–6.39 (m, 12H), 3.19 (sept, J=8.0 Hz,
4H), 1.50 (d, J=8.0 Hz, 12H), 1.16 ppm (d, J=8.0, 12H); 13C NMR
(75 MHz, C6D6): d=169.2, 151.7, 147.5, 146.8, 136.7, 135.0, 132.5, 130.0,
126.3, 124.6, 124.1, 122.2, 121.0, 29.3, 26.5, 23.2 ppm; HRMS (EI): m/z
calcd. for C44H53N3S2Pd [M+H]+: 792.2637; found: 792.2648.
a
Teflonꢂ-lined screw cap and the heated to 1008C for 16 h. The
1H NMR spectrum of this transformation indicated 62% conversion of
31 to 33. At this time, the solvent was removed under reduced pressure
and the product was purified using column chromatography (pentane/
EtOAc 30:1, Rf =0.35) providing (12 mg, 59%) as a dark-orange solid.
M.p. 198–2008C; 1H NMR (300 MHz, CDCl3): d=7.32–7.28 (m, 6H),
6.88 (brs, 3H), 6.70 (d, J=9.0 Hz, 3H), 7.37 (d, J=9.0 Hz, 2H), 5.66 (d,
J=9.0 Hz, 2H), 2.16 (s, 3H), 1.91 (s, 3H), 1.61 (brs, 4H), 1.44 (d, J=
6.0 Hz, 6H), 1.14 (d, J=6.0 Hz, 6H), 0.81 ppm (d, J=6.0 Hz, 12H);
13C NMR (75 MHz, CDCl3): d=174.7, 146.4, 145.7, 140.8, 136.7, 135.5,
134.0, 133.4, 131.8, 130.7, 129.6, 127.7, 126.7, 125.0, 124.1, 29.7, 28.7, 28.4,
26.2, 23.5, 22.6, 21.0, 20.8 ppm; HRMS (EI): m/z calcd for C34H43N2S
[MÀSC7H7]+: 511.3146; found: 511.3142.
Synthesis of complex 29: Following
the general procedure, 20 (101 mg,
0.15 mmol)
and
10
(3 equiv,
0.45 mmol) were reacted at 508C for
18 h. The supernatant obtained from
the centrifugation process was evapo-
rated and the product was purified by
crystallising 29 out of solution using
Reaction between 32 and 33 in the
presence of KOtBu to produce 35
[Eq. (2)]: In the glovebox an NMR
tube was loaded with 31 (100 mg,
0.122 mmol) and KOtBu (72.5 mg,
pentane/CH2Cl2 at À208C, which left 36 in the mother liquor as a clean
product. Solvent removal provided 36 (41 mg, 30%) as a dark-orange
powder. M.p. 140–1438C; 1H NMR (400 MHz, C6D6): d=7.50–7.39 (m,
6H), 6.74–6.72 (m, 6H), 6.61 (t, J=9.0 Hz, 2H), 6.51 (t, J=9.0 Hz, 4H),
6.26 (t, J=6.0 Hz, 1H), 5.81 (d, J=6.0, 2H), 3.62 (sept, J=6.0 Hz, 4H),
2.59 (s, 6H), 1.71 (d, J=6.0 Hz, 12H), 1.12 ppm (d, J=6.0 Hz, 12H);
13C NMR (75 MHz, C6D6): d=170.4, 158.2, 147.1, 144.9, 137.2, 135.8,
135.5, 129.8, 128.1, 126.5, 124.9, 123.9, 122.7, 121.2, 29.3, 27.4, 26.5,
22.9 ppm; HRMS (EI): m/z calcd for C40H50N3SPd [MÀSC6H5]+:
710.2760; found: 710.2770; X-ray crystallographic analysis is included
below.
5 equiv, 0.61 mmol).
A septum was
placed on top of the tube and once
outside the glovebox 32 (57 mg,
2 equiv, 0.244 mmol) was added under argon atmosphere followed by
C6D6 (1 mL). The tube was left to stand in an oil bath at 608C for 16 h at
1
which time a H NMR spectrum was recorded that revealed 22% conver-
sion to 34 had taken place The solvent was removed under reduced pres-
sure and the product was purified by column chromatography (pentane/
diethyl ether 7:1, Rf =0.24) providing 34 (19 mg, 20%) as a dark-yellow
Synthesis of complex 30: Following the general procedure, 13 (97 mg,
0.15 mmol) and 10 (3 equiv, 0.45 mmol) were reacted at room tempera-
1
solid. M.p. 171–1738C; H NMR (400 MHz, C6D6): d=9.66 (d, J=5.2 Hz,
1H), 7.43 (d, J=7.6 Hz, 2H), 7.29–7.24 (m, 2H), 7.25–7.07 (m, 8H), 6.89
(s, 2H), 6.79 (d, J=8.0 Hz, 1H), 6.68 (d, J=7.6 Hz, 2H), 6.54 (t, J=
8.0 Hz, 1H), 6.09 (t, J=8.0 Hz, 1H), 3.84 (sept, J=6.8 Hz, 2H), 3.42
(sept, J=6.4 Hz, 2H), 2.19 (s, 3H), 1.89 (d, J=6.8 Hz, 6H), 1.24 (d, J=
6.8 Hz, 6H), 1.16 (d, J=6.4 Hz, 6H), 1.09 ppm (d, J=6.4 Hz, 6H);
13C NMR (100 MHz, C6D6): d=181.2, 165.5, 164.0, 151.3, 147.5, 147.4,
147.0, 144.8, 138.3, 136.8, 136.3, 132.3, 129.8, 128.4, 127.6, 124.8, 124.1,
123.9, 123.2, 122.8, 121.2, 117.1, 29.2, 28.4, 26.7, 26.0, 23.1, 22.9, 20.6 ppm;
HRMS (EI): m/z calcd for C38H44N3Pd [MÀC6H5S]+: 648.2567; found:
648.2589.
ture for 2 h. The supernatant obtained from the centrifugation process
was evaporated and the product was crystallised from pentane/CH2Cl2,
chilled at À 208C for 1 h to give 29 as a clean product leaving 28 in the
mother liquor. Compound 29 (35 mg, 40%) were isolated as a yellow
powder. M.p. 2838C (decomp); 1H NMR (400 MHz, CDCl3): d=7.31–
7.26 (m, 4H), 7.16–7.11 (m, 12H), 6.07 (d, J=8.0 Hz, 4H), 6.89–6.79 (m,
14H), 6.37 (brs, 12H), 3.19 (s, J=6.8 Hz, 8H), 1.27 (d, J=6.8, 24H),
1.05 ppm (d, J=6.8, 24H); 13C NMR (75 MHz, C6D6): d=175.9, 151.9,
148.2, 146.4, 136.2, 132.1, 130.9, 129.3, 127.1, 125.9, 124.2, 123.3, 120.5,
119.3, 28.8, 26.5, 22.4 ppm.
Acknowledgements
The authors are grateful to the National Science and Engineering Coun-
cil of Canada (NSERC) and the Ontario Research and Development
Challenge Fund (ORDCF).
Synthesis of complex 32: Following the general procedure, 13 (97 mg,
0.15 mmol) and tolylthiol (3 equiv, 0.45 mmol) were reacted at room tem-
perature for 1 h. The supernatant obtained from the centrifugation proc-
ess was evaporated and the product was purified by crystallising impuri-
Chem. Eur. J. 2013, 00, 0 – 0
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
7
&
ÞÞ
These are not the final page numbers!

M. G. Organ et al.
data can be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[9] a) M. Pompeo, N. Hadei, R. D. J. Froese, M. G. Organ, Angew.
Chem. Int. Ed. 2012, 51, 11354–11357; b) K. H. Hoi, J. A. Coggan,
M. G. Organ, Chem. Eur. J. 2012, 18, In Press.
[10] a) K. H. Hoi, S. C¸ alimsiz, R. D. J. Froese, A. C. Hopkinson, M. G.
Organ, Chem. Eur. J. 2012, 18, 145–151; b) C. Valente, S. C¸ alimsiz,
K. H. Hoi, D. Mallik, M. Sayah, M. G. Organ, Angew. Chem. Int.
Ed. 2012, 51, 3314–3332; c) K. H. Hoi, S. C¸ alimsiz, R. D. J. Froese,
A. C. Hopkinson, M. G. Organ, Chem. Eur. J. 2011, 17, 3086–3090;
d) S. C¸ alimsiz, M. G. Organ, Chem. Commun. 2011, 47, 5181–5183;
e) S. C¸ alimsiz, M. Sayah, D. Mallik, M. G. Organ, Angew. Chem.
2010, 122, 2058–2061; Angew. Chem. Int. Ed. 2010, 49, 2014–2017;
f) M. Dowlut, D. Mallik, M. G. Organ, Chem. Eur. J. 2010, 16, 4279–
4283; g) M. G. Organ, S. C¸ alimsiz, M. Sayah, K. H. Hoi, A. J. Lough,
Angew. Chem. 2009, 121, 2419–2423; Angew. Chem. Int. Ed. 2009,
48, 2383–2387.
[1] a) M. C. Bagley, T. Davis, M. C. Dix, V. Fusillo, M. Pigeaux, M. J.
Rokicki, D. Kipling, J. Org. Chem. 2009, 74, 8336–8342; b) G. De
Martino, M. C. Edler, G. La Regina, A. Coluccia, M. C. Barbera, D.
Barrow, R. I. Nicholson, G. Chiosis, A. Brancale, E. Hamel, M.
Artico, R. Silvestri, J. Med. Chem. 2006, 49, 947–954.
[2] M. A. Fernꢄndez-Rodrꢅguez, J. F. Hartwig, Chem. Eur. J. 2010, 16,
2355–2359 and references cited therein.
[3] a) M. Kosugi, T. Shimizu, T. Migita, Chem. Lett. 1978, 13–14;
b) M. A. Fernꢄndez-Rodrꢅguez, Q. Shen, J. F. Hartwig, Chem. Eur. J.
2006, 12, 7782–7796; c) M. Murata, S. L. Buchwald, Tetrahedron
2004, 60, 7397–7403; d) G.-Y. Gao, A. J. Colvin, Y. Chen, X. P.
Zhang, J. Org. Chem. 2004, 69, 8886–8892; e) L. Cai, J. Cuevas, Y.-
Y. Pengb, V. W. Pike, Tetrahedron Lett. 2006, 47, 4449–4452; f) P. G.
Ciattini, E. Morera, G. Ortar, Tetrahedron Lett. 1995, 36, 4133–
4136; g) U. Schopfer, A. Schlapbach, Tetrahedron 2001, 57, 3069–
3073.
[4] E. Alvaro, J. F. Hartwig, J. Am. Chem. Soc. 2009, 131, 7858–7868.
[5] M. Sayah, M. G. Organ, Chem. Eur. J. 2011, 17, 11719–11722.
[6] a) C. J. OꢆBrien, E. A. B. Kantchev, N. Hadei, C. Valente, G. A.
Chass, J. C. Nasielski, A. Lough, A. C. Hopkinson, M. G. Organ,
Chem. Eur. J. 2006, 12, 4743–4748; b) M. G. Organ, S. Avola, I. Du-
bovyk, N. Hadei, E. A. B. Kantchev, C. J. OꢆBrien, C. Valente,
Chem. Eur. J. 2006, 12, 4749–4755.
[11] Pd-PEPPSI-IPentCl, which has a 3-chloropyrdine moiety, (see ref.
[9]) and the 2-methylpyridine derivative 27, which is especially easy
to activate, are both available through Total Synthesis Ltd. In Tor-
onto, see: totalsynthesis.ca.
[12] For reaction conditions used in the NMR studies, see the Supporting
Information.
[13] When the reaction was performed under the same conditions but
for 30 min instead of 2 h, only 28 was formed as determined by
1H NMR spectroscopy. Therefore, the formation of 28 and 30 show
time dependency, that is, 28 forms first and then 30 starts to form,
apparently from 28.
[7] For a structure–activity relationship (SAR) analysis of the pyridine
ligand in PEPPSI precatalyst activation, see: J. Nasielski, E. A. B.
Kantchev, C. J. OꢆBrien, M. G. Organ, Chem. Eur. J. 2010, 16,
10844–10853.
[8] For the crystal structure of the disulfide complex derived from 12,
and key structural information (e.g., bond lengths), see the Support-
ing Information. CCDC-898001, 898000 (28) and 898002 (29) con-
tain the supplementary crystallographic data for this paper. These
[14] M. A. Fernꢄndez-Rodrꢅguez, J. F. Hartwig, J. Org. Chem. 2009, 74,
1663–1672.
Received: September 5, 2012
Published online: && &&, 0000
&
8
&
www.chemeurj.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Sulfination by Using Pd-PEPPSI Complexes
FULL PAPER
Pd-Catalysed Sulfination
M. Sayah, A. J. Lough,
M. G. Organ* .................... &&& — &&&
Sulfination by Using Pd-PEPPSI
Complexes: Studies into Precatalyst
Activation, Cationic and Solvent
Effects and the Role of Butoxide Base
On activation duty: The activation of
PEPPSI precatalysts has been evalu-
ated in the sulfination of aryl halides
(see figure). Substitution of the two
chlorides on Pd with two sulfides
occurs immediately, even at low tem-
perature, and it is this species that is
reduced and enters the catalytic cycle.
Butoxide base is involved in precata-
lyst activation and maintaining a
healthy level of active catalyst to
ensure high catalytic performance.
Examination of the cation of the sul-
fide salt and solvent dielectric revealed
that solubility is very important to the
success of this transformation.
Chem. Eur. J. 2013, 00, 0 – 0
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
9
&
ÞÞ
These are not the final page numbers!