The palladium(ii) complex of N,N-diethyl-1-ferrocenyl-3-thiabutanamine: Synthesis, solution and solid state structure and catalytic activity in Suzuki-Miyaura reaction

Article abstract of DOI:10.1039/c4ra08140d

In this paper we wish to present the first results on the synthesis of N,N-diethyl-1-ferrocenyl-3-thiabutanamine, its coordination with palladium(ii), the complete characterization of the thus obtained complex (including single crystal X-ray analysis for the complex in two polymorphic forms) and screening of its catalytic activity in Suzuki-Miyaura coupling of phenylboronic acid with several aryl bromides. The complex, either purified and then added to the reaction mixture or generated in situ, proved to be an excellent precatalyst in Suzuki-Miyaura coupling. The chemical behavior of the complex in solution was assessed by detailed NMR analyses and cyclic voltammetry measurements which allowed us to draw a number of mechanistic conclusions. This journal is

Full text of DOI:10.1039/c4ra08140d

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PAPER
The palladium(II) complex of N,N-diethyl-1-
ferrocenyl-3-thiabutanamine: synthesis, solution
and solid state structure and catalytic activity in
Suzuki–Miyaura reaction†
Cite this: RSC Adv., 2014, 4, 43792
a
a
a
b
a
Ivan Damljanovic, Dragana Stevanovic, Anka Pejovic, Danijela Ilic, Marija Zˇ ivkovic,
´
´
´
´
´
a
c
d
e
Jovana Jovanovic, Mirjana Vukicevic, Goran A. Bogdanovic, Niko S. Radulovic*
´
´
´
´
´
a
and Rastko D. Vukicevic*
´
´
In this paper we wish to present the first results on the synthesis of N,N-diethyl-1-ferrocenyl-3-
thiabutanamine, its coordination with palladium(II), the complete characterization of the thus obtained
complex (including single crystal X-ray analysis for the complex in two polymorphic forms) and
screening of its catalytic activity in Suzuki–Miyaura coupling of phenylboronic acid with several aryl
bromides. The complex, either purified and then added to the reaction mixture or generated in situ,
proved to be an excellent precatalyst in Suzuki–Miyaura coupling. The chemical behavior of the complex
in solution was assessed by detailed NMR analyses and cyclic voltammetry measurements which allowed
us to draw a number of mechanistic conclusions.
Received 18th July 2014
Accepted 29th August 2014
DOI: 10.1039/c4ra08140d
www.rsc.org/advances
3
chemistry, and complexes of transition metals with such
ligands are widely used as catalysts in organic synthesis.
Introduction
2
Among unnatural compounds, ferrocene and its derivatives Hence, the synthesis of ferrocene derivatives containing one
have captured particular attention from many chemists due to or more additional heteroatoms (monodentate ligands
several unique properties of this metallocene. Utilizing clas- capable of coordinating with transition metals' cations, or
sical methods of organic synthesis (initiated by Woodward's polydentate ligands capable of forming chelates with these
1
discovery of Friedel–Cras acylation of ferrocene ), a plethora cations, respectively) is of high interest for a wide range of
of ferrocene derivatives have been synthesized until now. chemists. Recently, we reported on the synthesis of several
4
These compounds are highly appreciated due to their acylferrocenes containing a sulfur atom in their alkyl chains.
outstanding stability in both aqueous and non-aqueous Considering the known reactivity of the carbonyl group,
media, and have applications in numerous elds, particularly acylferrocenes containing a heteroatom in alkyl chains are
2
in synthesis and catalysis. A multitude of ferrocene-con- much appreciated synthetic starting materials. For example,
taining ligands are of great interest in coordination the synthetic value of such compounds has recently been
recognized through the use of sulfonium salts of 1-ferrocenyl-
3
-thiabutan-1-one and 1-ferrocenyl-4-thiapentan-1-one in
a
5
Department of Chemistry, Faculty of Science, University of Kragujevac, R. Domanovi ´c a cyclopropanation reactions of conjugated enones or substi-
1
2, 34000 Kragujevac, Serbia. E-mail: vuk@kg.ac.rs; Fax: +381-34-34-50-40; Tel:
381-34-30-02-68
6
tution reactions with diverse nucleophiles. The synthesis of
+
b
compounds containing a new carbon–carbon bond is the
particular advantage of the last reaction. Furthermore, the
alcohols obtained by the reduction of these compounds can
undergo different reactions based on the known stability of
Faculty of Technical Sciences Kosovska Mitrovica, University of Pri ˇs tina, Kneza Milo ˇs a
7
, 38220 Kosovska Mitrovica, Serbia
c
Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, S.
Markovi ´c a 69, 34000 Kragujevac, Serbia
d
Vin ˇc a Institute of Nuclear Sciences, University of Belgrade, PO Box 522, 11001 carbocations bearing a ferrocenyl group. One of the possible
Belgrade, Serbia
synthetic applications of sulfur-containing acylferrocenes is
e
Department of Chemistry, Faculty of Science and Mathematics, University of Ni ˇs ,
the synthesis of bidentate ligands (with sulfur as one of the
Vi ˇs egradska 33, 18000 Ni ˇs , Serbia. E-mail: nikoradulovic@yahoo.com; Fax: +381-
two coordinating heteroatoms) by a formal substitution of the
1
†

8-533-014; Tel: +381-62-80-49-210
hydroxyl group with certain nucleophiles, e.g. with an amino
nitrogen. Such compounds could serve as good phosphine-
Electronic supplementary information (ESI) available: Spectroscopic data, CIF
1
13
les and copies of
H
and
C NMR spectra for all newly synthesized
compounds, as well as X-ray crystallographic data for 6. CCDC 1016148 and free ligands for catalysts promoting the formation of new
016149. For ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c4ra08140d
1
carbon–carbon bonds.
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Setting up the carbon backbone is one of the basic synthetic
RSC Advances
tasks and, therefore, the formation of new carbon–carbon
7
bonds lies at the heart of organic synthesis. Among many
reactions used for this purpose, metal-mediated couplings
represent important tools in carbon–carbon bond formation
and are widely used in various chemical and pharmaceutical
8
processes. Since its discovery, the Suzuki–Miyaura coupling
represents one of the most important and widely used reactions
8
c,9
in the synthesis of diverse biaryls. The most frequently used
catalysts for this purpose are palladium complexes with phos-
phine ligands, among which numerous ferrocene-containing Scheme 2 Synthesis of complex 6.
2,10
coordination complexes.
The disadvantages of utilizing
phosphines as ligands for Pd are numerous, including their
sensitivity, high expense, and lack of commercial sources for Namely, this method includes the acetylation of an a-ferroce-
late generation compounds. Perhaps most importantly, few nylalkanol and the subsequent substitution of the acetate from
catalysts exhibit superior activity among broad substrate classes the obtained ester with an amino group. The outstanding
and reaction paradigms. It should also be noted that Pd(PPh
3
)
4
stability of the a-ferrocenylcarbocation, i.e. the involvement of
is widely applied in catalysis, but this complex suffers from poor the ferrocene core in stabilizing either the intermediate or the
stability upon storage as well as advised handling under transition state, most likely plays the decisive role in directing
1
1
nitrogen.
the reaction into the desired course (alkylation of the nitrogen
atom). In this way the hydroxysulde 3 (via its acetate 4) was
converted into the aminosulde 5 (Scheme 2) in moderate yield
Results and discussion
(
47% based on 3). The structures of the new compounds (ester 4
1
and aminosulde 5) were corroborated by spectral data (IR, H
and C NMR).
In the present communication we wish to outline the rst
results on the synthesis of N,N-diethyl-1-ferrocenyl-3-thiabu-
tanamine, its coordination with palladium(II), the complete
characterization of the thus obtained complex and screening of
its catalytic activity in Suzuki–Miyaura couplings of phenyl-
boronic acid with several aryl bromides.
This study started with the synthesis of 1-ferrocenyl-3-thia-
butan-1-one (2) by acylation of ferrocene (1) with the in situ
generated chloride of S-methylthioglycolic acid (utilizing the
1
3
In the next step the S,N-bidentate ligand 5 was coordinated
to palladium(II) ions by reacting this aminosulde with potas-
sium tetrachloropalladate in a two-phasic solvent system
(water/chloroform), giving the complex 6 in 88% yield.
Crystals of complex 6 suitable for X-ray analysis were
obtained by slow evaporation of solvents from an ethanol–
dichloromethane solution of 6. Compound 6 crystallized with
one molecule of ethanol in the asymmetric unit of 6$EtOH
4,12
procedure developed by us ), and the subsequent reduction of
this ketone by sodium borohydride in methanol to 1-ferrocenyl-
-thiabutan-1-ol (3) (Scheme 1).
(polymorph I). Fig. 1 shows the molecular diagram of this
13
compound with the atom numbering and selected bond lengths
and angles. Crystal data and structure renement are described
3
The obtained hydroxysulde 3 was the key intermediate
towards the target complex, since the simple substitution of its
hydroxyl group with a diethylamino one (the key reaction)
should give the target ligand – a bidentate ligand containing an
amine nitrogen and a sulde sulfur atom. Prompted by the
recent literature report of a successful direct substitution of the
hydroxyl group of 1-ferrocenylethanol with several N-, S- and
14
even C-nucleophiles catalyzed by bismuth(III) nitrate, we
submitted the alcohol 3 and diethylamine to the conditions
described therein (Scheme 2).
However, in our hands this procedure failed to provide the
target product, and we decided to apply the forty-year-old
procedure utilized in an indirect substitution of the hydroxyl
15
group from
a 1-ferrocenylalkanol with dimethylamine.
Fig. 1 The molecular structure of 6 with atom numbering scheme
(hydrogen atoms and ethanol solvent molecule are omitted for clarity).
Displacement ellipsoids are drawn at the 30% probability level. Other
projections of the molecule are given in Fig. S1 (see ESI†). Selected
ꢀ
bond lengths ( A˚ ) and angles ( ): Pd1–N1 ¼ 2.107(3), Pd1–S1 ¼
2
.2350(10), Pd1–Cl1 ¼ 2.3016(11), Pd1–Cl2 ¼ 2.3387(11), N1–C16 ¼
1
8
.496(5), N1–C14 ¼ 1.504(5), N1–C11 ¼ 1.543(5); N1–Pd1–S1 ¼
7.92(8), N1–Pd1–Cl1 ¼ 174.67(9), S1–Pd1–Cl1 ¼ 86.77(4), N1–Pd1–
Scheme 1 Synthesis of alcohol 3.
Cl2 ¼ 93.73(8), S1–Pd1–Cl2 ¼ 178.34(4), Cl1–Pd1–Cl2 ¼ 91.58(5).
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in ESI.† The ferrocenyl ligand binds to Pd(II) through N1 deduced from the unassigned NMR data. The observed down-
nitrogen and S1 sulfur atoms, thus conrming a bidentate (N,S) eld shi could be explained by the expected electron-with-
coordination mode of the ligand. The remaining coordination drawing effect of palladium(II), i.e. the overall electron density
sites of Pd(II) are occupied by two chlorines. All four atoms in should be more toward the metal halide which in effect would
the Pd coordination sphere and Pd1 atom are almost ideally make the coordinating atoms electron-decient compared to
coplanar (root-mean-square deviation of the ve atoms is only the free ligands.
˚
0
.005 A). However, the square-planar geometry around Pd(II) is
As depicted in Fig. 1, complex 6 in solid state has a cis-
rather distorted since the coordination angles signicantly conguration (the methyl group at the sulfur atom and the
ꢀ
deviate from 90 . Thus, N1–Pd1–Cl2 and S1–Pd1–Cl1 are ferrocenyl group are on the same side of the PdSCCN ring).
ꢀ
9
3.73(8) and 86.77(4) , respectively. Two Pd–Cl bonds show a However, its NMR spectra in CDCl always corresponded to a
3
˚
difference in bond lengths of almost 0.4 A.
two component mixture of constant composition (1 : 1). Aer a
1
13
The ve-membered Pd1–N1–C11–C12–S1 chelate ring adopts detailed analysis of both 1D- ( H, C and DEPT) and 2D-
a twisted conformation with the N1–C11–C12–S1 torsion angle ( H– H–COSY, NOESY, HSQC and HMBC) NMR spectra, and a
of 51.3(4) . Both ethyl groups bonded to N1 atom have very series of selective homodecoupling experiments, all of the
1
1
ꢀ
similar space directionality and an almost orthogonal orienta- observed signals were successfully assigned to the two diaste-
tion in relation to the Pd(II) coordination plane. Dihedral angle reomeric 6, differing in the relative stereochemistry around the
between the N1–C14–C15 and N1–C16–C17 mean planes is chelate ring. The signals of methylthio protons of both diaste-
ꢀ
˚
1
2.0(5) . The N1–C11 bond has bond length which is about 0.4 A reomers at 2.75 and 2.80 ppm (cis and trans, respectively) were
longer than for the N1–C14 and N1–C16 bonds. Bond lengths the entry points in 2D spectra that corroborated the expected
and angles of the ferrocenyl unit agree with those expected for connectivity of the molecules. Crucial pieces of information that
monosubstituted ferrocene derivatives. The two cyclo- enabled an almost complete assignation of the trans-isomer
pentadienyl rings (Cp) are planar and nearly parallel. Dihedral (Table 1) came from the NOESY spectrum. More precisely, the
ꢀ
angle between two Cp rings is 2.5(5) . The Cp rings signicantly nOe crosspeak between SCH
3
group protons and H-1 proton,
deviate from an eclipsed conformation (see Fig. S1 in the ESI†). both of which simultaneously interacted with H-2a, suggested a
ꢀ
The C1–Cg1–Cg2–C6 torsion angle is 21.3 (Cg1 and Cg2 are spatial proximity of the mentioned hydrogens. The values of the
centroids of the corresponding Cp rings).
coupling constants of H-1 and H-2a or H-2b (cis-6 J (H-1-H-2a) ¼
3
In the crystal, molecules of 6 form very interesting dimers. 4.3 Hz, J (H-1-H-2b) ¼ 13.4 Hz, trans-6 J (H-1-H-2a) ¼ 12.8 Hz)
3
3
The rst centrosymmetric dimer (Fig. S2†) possesses two Pd/S corroborate this stereochemical relationship. The coordination
i
˚
intermolecular contacts with the Pd1/S1 distance (3.76 A) to Pd produced a new chiral center (S atom) and caused a
close to the sum of van der Waals radii. The Pd1/S1 vector differentiation of the protons from the ethyl groups (both CH
i
2
[
symmetry code: (i) ꢁx + 1, ꢁy + 1, ꢁz + 2] agrees very well with and CH
3
now gave rise to a myriad of signals – 4 different methyl
the potential directionality of the lone pair at the sulfur atom. group triplets and 8 doublets of quartets originating from the
Also the location of S1 corresponds to the apical position in the diastereotopic CH protons), and this also clearly demonstrates
2
i
coordination sphere of Pd1. This probably stabilizing intermo- the existence of the cis- and trans-6. Due to strong mutual
lecular interaction within the dimer is also supplemented by overlap the only unresolved protons le in the spectra (in the
several C–H/Cl, C–H/O and O–H/Cl intermolecular inter- sense to which of the two isomers they belong to) were those of
actions (Fig. S3†). Some of these interactions are formed the ferrocene moiety.
through two EtOH molecules. Practically all signicant inter-
The existence of two diastereoisomers of 6 (of equal ther-
atomic interactions are located within this dimer.
modynamic stability) in solution at room temperature can be
Another interesting dimer is formed between two ferrocene interpreted in two ways: they interconvert rapidly in solution
units placed in parallel orientation (Fig. S4†). Recently it has and one of the isomers is less soluble than the other, or the
16
been reported that almost 60% of crystal structures containing solid state is also consisted of crystals of both cis- and trans-6.
monosubstituted ferrocene (Fc) form a Fc–Fc dimer as a Since complex 6 displays sharp signals of both isomers in the
common building block. It has been shown that two Fc units NMR spectra, the rate of interconversion could be either very
within the dimer exhibit an excellent electrostatic comple- slow or could be in the domain of medium slow (up to about a
2
˚
mentarity in a very large contact surface of about 6 ꢂ 3 A . Such minute) exchanges, yielding sharp separate spectra but also
a dimer also exists in the crystal structure of 6$EtOH (Fig. S4†). exchange peaks in the NOESY spectrum. Since the later were
In that way the crystal packing of 6$EtOH is stabilized by the observed in our spectra (for example the interaction of H-1 at
formation of two types of dimers as dominant building blocks. 4.73 and 4.22 ppm from trans- and cis-6, respectively), we could
One formed by Pd coordination sphere and another one formed conclude that the equilibrium shown in Scheme 3 is medium
ꢀ
by the ferrocene unit.
slow in CDCl at 25 C.
3
1
13
H and C NMR spectra of complex 6 were noticeably
Apparently, the cis-/trans-diastereoisomers of 6 interconvert
different from that of the uncoordinated ligand; addition of the relatively easily in the solution, whereas it seems that only the
free ligand resulted in another set of proton (Table 1) and cis-isomer crystallizes out of solution. In order to acquire an
carbon-13 (Table 2) signals with the expected chemical shis. additional evidence for this, complex 6 was recrystallized from
1
13
The palladation of the ligand resulted in a mean H and
C
several other solvents and solvent mixtures. Only recrystalliza-
deshielding (mean D
H
: +0.80 ppm, mean D
C
: +2.7 ppm) as tion from methanol gave another crystal polymorph(II) with
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1
Table 1 H chemical shifts, multiplicities and coupling constants (JH–H) for 5, cis-6 and trans-6 in CDCl
3
(400 MHz)
Trans-6
a
a
Hydrogen
1
5
Cis-6
3.87 (dd, J ¼ 9.9, 4.4 Hz, 1H)
3.07 (dd, J ¼ 12.8, 4.4 Hz, 1H)
3.01 (dd, J ¼ 12.8, 9.9 Hz, 1H)
2.25 (s, 3H)
ꢃ4.22 (overlapped, 1H)
4.73 (dd, J ¼ 13.4, 4.3 Hz, 1H)
3.67 (dd, J ¼ 15.1, 13.4 Hz, 1H)
2
CH
CH
CH
a
H
b
S
3.67 (dd, J ¼ 12.6, 3.4 Hz, 1H)
3.35 (dd, J ¼ 13.8, 12.6 Hz, 1H)
b
b
a
H
b
S
3.21 (dd, J ¼ 15.1, 4.3 Hz, 1H)
b
3
S
2.75 (s, 3H)
2.80 (s, 3H)
N(CH
2
CH
3
)
)
2
2.48 (dq, J ¼ 12.9, 7.3 Hz, 2H,
3.49 (dq, J ¼ 13.2, 7.0 Hz, 1H,
3.59 (dq, J ¼ 13.2, 7.2 Hz, 1H,
N(CH
a
H
b
CH
3
)
2
)
a
CH H
b 3
CH )
a b 3
CH H CH )
2
.94 (dq, J ¼ 13.2, 7.5 Hz, 1H,
2.63 (dq, J ¼ 13.1, 7.3 Hz, 1H,
b
b
CH
2.30 (dq, J ¼ 13.2, 6.7 Hz, 1H,
CH CH
.43 (dq, J ¼ 13.2, 6.9 Hz, 1H,
a
H
b 3
CH )
CH
2.15 (dq, J ¼ 13.2, 6.4 Hz, 1H,
CH CH
2.52 (dq, J ¼ 13.1, 7.3 Hz, 1H,
a b 3
H CH )
2
.06 (dq, J ¼ 12.9, 7.0 Hz, 2H,
N(CH
H
a b
CH
3
)
2
)
a
H
b
3
)
a
H
b
3
)
2
CH
b
b
a
b 3
H CH )
a b 3
CH H CH )
N(CH
2
CH
3
2
1.01 (brt, J ¼ 7.1 Hz, 6H)
1.87 (brt, J ¼ 6.8 Hz, 3H)
1.88 (brt, J ¼ 6.8 Hz, 3H)
b
b
1
.76 (brt, J ¼ 7.2 Hz, 3H)
1.67 (t, J ¼ 7.3 Hz, 3H)
C
5
H
4
4.04 (dt, J ¼ 2.3, 1.3 Hz, 1H), 4.14–
4.41–4.32 (Overlapped, 4H), 4.31–
4.25 (overlapped, 3H), 4.24–4.18
4.09 (overlapped, 3H)
(overlapped, 1H)
C
5
H
5
4.12 (s, 5H)
4.19 (s, 5H)
4.16 (s, 5H)
a
NMR spectra of 6$EtOH were identical to those reported in this table except for the additional presence of a triplet (1.24 ppm, J ¼ 7.0 Hz, 3H, CH
) pair of coupled signals and an exchangeable broad signal (1.21 ppm, brs, 1H, OH) pertaining to ethanol.
On the same side of the chelate ring as the ferrocenyl group.
3
)
and quartet (3.71 ppm, J ¼ 7.0 Hz, 2H, CH
2
b
13
Table 2
3
C chemical shifts for 5, cis-6 and trans-6 in CDCl (400 MHz)
a
a
Carbon
5
Cis-6
Trans-6
1
2
58.8
37.6
16.8
43.6
14.1
66.7
67.4
40.0
22.0
51.7, 52.1
14.2, 15.2
70.1
69.9, 69.4(1), 69.4(1)
75.7
69.5(7)
43.5b
3
CH S
N(CH
N(CH
C
24.0
b
b
b
2
CH
3
)
)
2
2
53.3, 52.9b
13.9, 15.3
67.5
68.2, 69.3(7), 69.6(4)
76.2
2
CH
3
5
H
4
0
68.6
0
(C-2 -C-5 )
67.2(3), 67.2(0), 66.9
86.4
68.6
0
(C-1 )
C
5
H
5
69.6(4)
a
3
NMR spectra of 6 EtOH were identical to those reported in this table except for the additional presence of two signals at 18.5 ppm (CH ) and 58.5
b
2
ppm (CH ) corresponding to ethanol. On the same side of the chelate ring as the ferrocenyl group.
non-solvated Pd complex molecules (see ESI†). Although these through the breaking of the S–Pd bond, as depicted in
crystals were of poor crystallographic quality (racemic twinning) Scheme 3.
the single-crystal X-ray analysis conrmed undoubtedly the cis-
Redox properties of ligand 5 and complex 6 were evaluated
conguration of 6 in this crystal polymorph (see Fig. S5†) as it by cyclic voltammetry in a 0.1 M dichloromethane solution of
was found in the crystal structure of 6$EtOH (Fig. 1). The main tetrabutylammonium perchlorate (at a glassy carbon disc
conformational difference of the Pd complex in two polymorphs working electrode). On the basis of preliminary measurements
is the mutual orientation of the ethyl groups bonded to the N1 we have chosen a ꢁ1.500/+1.500 V potential window and the
ꢁ
1
atom (Fig. S7†). Since thiomorpholine and Pd(II) form a PdL
2
X
2
scan rate n ¼ 0.2 V s . As depicted in Fig. 2 (the rst and second
17
complex with proven N-coordination, the equilibrium between scan, curves a and b, respectively), ligand 5 exhibits four
the two diastereoisomers in solution proceeds most likely oxidation (O1–4) and four reduction waves (R1–4). When the
potential swept up to 0.800 V, only O2 and R2 were observed
(curve c), and we attributed these waves to the ferrocene unit.
The redox potential of this couple is the same as for the
unsubstituted ferrocene under the same conditions (curve d).
The true nature of processes responsible for waves O1, O3,
O4, R1, R3 and R4, for which the lone electron pairs of
heteroatoms are responsible, exceeds the scope of this paper.
Scheme 3 Equilibrium between diastereoisomers of 6 in solution.
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Scheme 4 Reduction of 6 at the working electrode and trapping of
0
the obtained Pd species.
0
wave disappeared (curve c), since Pd species underwent
oxidative addition giving a pentacoordinated complex (see
Scheme 4). This complex should undergo oxidation at higher
18
ꢁ1
ꢁ4
potentials, but in the present case the corresponding wave
cannot be seen due to overlapping with the O2 wave.
Fig. 2 Cyclic voltammetry (n ¼ 0.2 V s ) of 5 (5 ꢂ 10 M) in 0.1 M
Bu NClO at a glassy carbon disc electrode (2 mm diameter).
4
4
The catalytic utility of complex 6 in the Suzuki–Miyaura
reaction was evaluated in the following manner: isolated crys-
tals of this compound were used as the catalyst (1 mol%) in an
overnight reaction of phenylboronic acid (7) with bromo-
benzene (8a) in a 4 : 1 (v/v) DMF–water mixture (Scheme 5) in
2 3
the presence of K CO . The experiment conducted at room
temperature resulted in the synthesis of biphenyl 9a in 45%
ꢀ
yield, but the reaction run at 70 C gave this compound in
almost quantitative yield (Table 3, entries 1 and 2, respectively).
To make this procedure more attractive from the synthetic point
of view, i.e. more suitable for practical use, we repeated the
experiment without the isolation and purication of the cata-
lyst. Namely, to the mixture of equimolar amounts (0.01 mmol)
of ligand 5 and palladium(II) chloride (or acetate), stirred for two
ꢀ
hours in the same solvent at 70 C (bath temperature), bromo-
ꢁ1
ꢁ4
Fig. 3 Cyclic voltammetry (n ¼ 0.2 V s ) of 6 (5 ꢂ 10 M) in 0.1 M
Bu NClO at a glassy carbon disc electrode (2 mm diameter).
benzene (1 mmol), phenylboronic acid (1.2 mmol) and K CO3
2
4
4
were added, and stirring was continued overnight. The reaction
where the catalyst was generated in situ was as successful as the
previous one (entry 3, Table 3).
In order to evaluate the generality of this reaction, we
employed nine additional bromoarenes as substrates in this
reaction (8b–j, Scheme 5), but using the in situ generated cata-
lyst only. As the data listed in Table 3 show (entries 4–12),
The lack of these waves in the voltammogram of complex 6
Fig. 3), in which these electrons are engaged in the formation
of Pd–N and Pd–S coordinative bonds, conrms this claim. As
depicted in Fig. 3 (curve a), complex 6 exhibits two oxidation
waves on the forward potential sweep (O1 at 0.533 and O2 at
(
0.763 V, respectively) and two reduction waves on the back
potential sweep (R1 at 0.625 and R2 at 0.994 V, respectively). We
attributed the O2/R2 response of the working electrode (curve a)
to the ferrocene unit, which is slightly shied to higher oxida-
tion potentials in comparison with the ferrocene/ferrocenium
couple (curve b). This could be rationalized by the increase of
electronegativity of the coordinated nitrogen (as much as to
prevent its oxidation in the chosen potential window), which
changes the electronic properties of the carbon atom next to the
ferrocene unit, making it more electron-withdrawing.
The second electrochemically sensitive position of complex
6, the coordinated palladium ion, under the applied conditions,
exhibits one oxidation and one intensive reduction peak (O1
and R1, respectively). These waves reect the reduction of
II
0
coordinated Pd and subsequent oxidation of the obtained Pd
species. Following the idea described in the literature for
18
Pd(PPh
3
)
2
Cl
2
,
in the next experiment, cyclovoltammetry of
Scheme 5 The Suzuki–Miyaura couplings of phenylboronic acid with
organic halides catalyzed by complex 6.
complex 6 was conducted in the presence of iodobenzene. O1
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Table 3 The Suzuki–Miyaura couplings of phenylboronic acid with dichlorido-(N,N-diethyl-1-ferrocenyl-3-thiabutanamine)palla-
organic halides catalyzed by complex 6
dium(II) (6) can be used as an efficient precatalyst in the Suzuki–
a
b
Miyaura couplings of aryl bromides with phenylboronic acid.
On the other hand, p-nitrochlorobenzene (8k), the only aryl
chloride used in this study, under the same reaction conditions,
gave the corresponding biphenyl in considerably lower yield
Entry
Aryl halide
Product
Method
Yield (%)
1
2
3
4
5
6
7
8
9
8a
8a
8a
8b
8c
8d
8e
8f
8g
8h
8i
8j
8k
9a
9a
9a
9b
9c
9d
9e
9f
9g
9h
9i
9j
9k
A
B
C
C
C
C
C
C
C
C
C
C
C
45
99
99
99
99
94
87
98
96
87
98
83
50
(entry 13, Table 3).
The catalytic activity of palladium chelates is known, and
recently several complexes of this metal with N- or P-chelating
ligands were examined as catalysts in the Suzuki–Miyaura
19
reaction by both computational and experimental studies. The
proposed mechanism does not include the chelate ring
opening; applying these statements, the mechanism of the
catalytic action of complex 6 might be presented as depicted in
Scheme 6, pathway A. However, in the light of the above-
mentioned considerations regarding the easiness by which cis-
10
11
12
13
a
Method A: Isolated, monosolvated complex 6 was used as the catalyst
at room temperature; Method B: isolated, monosolvated complex 6 was and trans-6 interconvert (i.e. the existence of a labile ligand –S-
ꢀ
used as the catalyst at 70 C (bath temperature); Method C: in situ atom of compound 5), the mechanism similar to that accepted
ꢀ
formed complex
6
was used as the catalyst at 70
temperature). Isolated yield, based on the starting aryl halide.
C
(bath
18
b
for palladium complexes with monodentate ligands, i.e. the
mechanism including the chelate ring opening, should not be
disregarded (Scheme 6, pathway B).
Unlike traditional palladium phosphine and NHC (nucleo-
philic heterocyclic carbene) catalysts, compound 6 can be
stored outside an inert atmosphere. The precatalyst may be
weighed out on bench utilizing normal methods and can even
be subjected to a water workup without observable decompo-
1
sition by H NMR. This Pd(II) complex becomes active in situ
through reduction to the Pd(0) active catalyst—thus it can be
considered a ligand stabilized Pd(PPh ) alternative, minus the
3 4
handling deciencies.
Conclusions
In summary, we described herein the synthesis of a new ferro-
cene-containing chelate – dichlorido-(N,N-diethyl-1-ferrocenyl-
3-thiabutanamine)palladium(II) monosolvate (6) – which was
fully characterized by spectral data and single crystal X-ray
structure analysis. It has been shown that this complex is an
efficient catalyst for Suzuki–Miyaura couplings of phenyl-
boronic acid with aryl bromides. It also turned out that the in
situ generated complex is of the same catalytic activity as the
isolated one.
Experimental section
General remarks
All chemicals were commercially available and used as received,
except that the solvents were puried by distillation. Ultrasonic
cleaner Elmasonic S 10 (Elma, Germany), 30 W was used for the
ultrasonically supported synthesis. Chromatographic separa-
tions were carried out using silica gel 60 (Merck, 230–400 mesh
ASTM), whereas silica gel 60 on Al plates, layer thickness 0.2
mm (Merck) was used for TLC. Melting points (uncorrected)
were determined on a Mel-Temp capillary melting points
1
13
1
apparatus, model 1001. The H and C{ H} NMR spectra of the
samples in CDCl were recorded at room temperature on a
Scheme 6 The Suzuki–Miyaura couplings of phenylboronic acid with
organic halides catalyzed by complex 6.
3
Varian Gemini (200 MHz) and a Bruker Avance III 400 MHz
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1
13
(
H at 400 MHz, C at 101 MHz) NMR spectrometers. Chemical mL of an ethanol–dichloromethane mixture (6 : 1). The solvent
shis are expressed in d (ppm), relative to the residual solvent was le to slowly evaporate (several days) which gave 487.5 mg
1
3
ꢀ
protons or CDCl as internal standards (CHCl : 7.26 ppm for (0.88 mmol) of dark red crystals of 6$EtOH (88%). m.p. 163 C;
3
13
3
1
H and 77 ppm for C). Standard pulse sequences were used for IR (KBr): n ¼ 3468, 3082, 2964, 2923, 2875, 1631, 1452, 1416,
1
1
ꢁ1
2
D spectra ( H– H COSY, NOESY, HSQC and HMBC). IR 1043, 1032 cm ; for NMR data see Tables 1 and 2. Anal. calc.
FeNPdS (FW ¼ 554.69): C, 41.14; H,
1725-X spectrophotometer. Microanalysis of carbon and 5.63; N, 2.53. Found: C, 41.08; H, 5.56; N, 2.57%.
measurements were carried out with a Perkin-Elmer FTIR for 6$EtOH ¼ C19
H31Cl
2
3
hydrogen were carried out with a Carlo Erba 1106 micro-
Recrystallization from a methanol–dichloromethane mixture.
analyser; their results agreed favorably with the calculated The crude complex was dissolved in a minimal amount of a
values.
methanol–dichloromethane mixture (4 : 1, v/v) and placed into a
refrigerator. Aer three days the solvent was decanted and the
obtained crystals of unsolvated 6 (m.p. 163 C) dried on air. IR
ꢀ
Synthetic procedures
(
KBr): n ¼ 3082, 2998, 2956, 2922, 2875, 1639, 1452, 1416, 1230,
ꢁ1
1-Ferrocenyl-3-thiabutan-1-one (2) and 1-ferrocenyl-3-thia- 1106, 1043, 1032 cm ; for NMR data see Tables 1 and 2. Anal.
butan-1-ol (3). These compounds were synthesized according to calc. for 6 ¼ C17
H
25Cl
2
FeNPdS (FW ¼ 508.62): C, 40.14; H, 4.95; N,
4a,4b,13
previously described methods.
-Ferrocenyl-3-thiabutan-1-yl acetate (4). 276 mg (1 mmol) of
, 0.5 mL of pyridine and 0.5 mL of acetic anhydride were stirred
2.75. Found: C, 40.21; H, 5.02; N, 2.79%.
1
3
General procedures for Suzuki–Miyaura reaction
at room temperature overnight, and then quenched with 30 ml
of 2 M HCl. The mixture was extracted with diethyl ether (three
Methods A and B. 5.5 mg (0.01 mmol) of dichlorido-(N,N-
diethyl-1-ferrocenyl-3-thiabutanamine)palladium(II)
solvate (C17 OH; 6), 146 mg (1.2 mmol) of
FeNPdS ꢂ C
phenylboronic acid (7), 1 mmol of the corresponding aryl halide
mono-
20 mL portions), the organic layer washed with saturated
H
25Cl
2
2 5
H
NaHCO , water and brine, successively and dried overnight
3
(
anhydrous Na SO ). The solvent was evaporated and the
2 4
(
8a–f), 4 mL of DMF and 1 mL of H O were stirred overnight at
ꢀ
2
obtained ester (orange solid, m.p. 58 C) was used in the next
ꢀ
room temperature (Method A) or at 70 C (bath temperature)
1
synthetic step without purication. H NMR (200 MHz, CDCl
ppm): d ¼ 5.89 (dd, J ¼ 8.6, 4.4 Hz, 1H, CH), 4.28 (dd, J ¼ 3.3, 1.6
Hz, 1H, CH, C ), 4.19–
), 4.22 (dt, J ¼ 3.4, 1.8 Hz, 1H, CH, C
.16 (m, 2H, 2 ꢂ CH, C ), 4.15 (s, 5H, 5 ꢂ CH, C ), 2.96 (dd,
J ¼ 14.0, 4.4 Hz, 1H, CH ), 2.84 (dd, J ¼ 14.0, 8.6 Hz, 1H,
CH H ), 2.14 (s, 3H, CH ), 2.13 (s, 3H, CH ); C NMR (50 MHz,
3
,
(
Method B). Then, 70 mL of water was added to the reaction
mixture, and the resultant mixture extracted with diethyl ether.
Ethereal solution was dried overnight (anhydrous sodium
sulfate), the solvent evaporated and the residue chromato-
graphed (5 g silica gel/n-hexane). All obtained biphenyls were
5
H
4
5 4
H
4
5
H
4
5 5
H
a
H
b
1
3
a
b
3
3
1
known compounds and were identied on the basis of their H
CDCl , ppm): d ¼ 170.2, 86.6, 70.2, 68.7, 68.2, 67.9, 67.3, 66.6,
3
13
20–24
and C NMR spectra.
3
2
C
9.5, 21.1, 16.2; IR: IR (KBr): n ¼ 3096, 3082, 2973, 2929, 2916,
Method C. 2.8 mg (0.01 mmol) of palladium dichloride (or
.2 mg (0.01 mmol) of palladium diacetate), 4.0 mg (0.012
ꢁ1
832, 1726, 1369, 1254, 1241 cm . Anal. calc. for 4 ¼
18FeO
S (FW ¼ 318.21): C, 56.62; H, 5.70. Found: C, 56.58;
H, 5.66%.
3
15
H
2
mmol) of N,N-diethyl-1-ferrocenyl-3-thiabutanamine (5), 4 mL
ꢀ
of DMF and 1 mL of water were stirred at 70 C for 2 h. To this
15
N,N-Diethyl-1-ferrocenyl-3-thiabutanamine (5). The solu-
tion of 318 mg (1 mmol) of 4 and 182.5 mg (2.5 mmol) of
diethylamine in methanol (20 mL) was stirred overnight at
room temperature. The solvent and the excess of diethylamine
were evaporated, and then the residue acidied with 10 mL of
solution 146 mg (1.2 mmol) of phenylboronic acid (7) and 1
mmol of the corresponding aryl halide (8a–f) were added and
the obtained mixture stirred overnight at the same temperature.
The reaction mixture was worked up as in the previous experi-
ment (Methods A and B).
3 4
H PO solution (10%, w/w). The obtained mixture was extracted
with diethyl ether to remove the (possibly) unreacted acetate 4,
basied with NaOH (pH 10; litmus paper) and extracted with
ether (three 20 mL portions). The collected ether layers were
X-ray crystal structure analysis of 6
Dichlorido-(N,N-diethyl-1-ferrocenyl-3-thiabutanamine)pal-
dried overnight (anhydrous Na
2 4
SO ) and the solvent evaporated ladium(II) monosolvate (6$EtOH), polymorph I. Single-crystal
to give 156 mg (0.47 mmol) of 5 (viscous, orange oil; 47%). IR: n diffraction data for 6$EtOH were collected on an Agilent Gemini
ꢁ
1
˚
¼
3093, 2966, 2914, 2870, 2813, 2721 cm ; for NMR data see S diffractometer equipped with Mo Ka radiation (l ¼ 0.71073 A)
Tables 1 and 2. Anal. calc. for 5 ¼ C17 25FeNS (FW ¼ 331.30): C, at room temperature. Data were processed with CRYSALIS
1.63; H, 7.61; N, 4.23. Found: C, 61.57; H, 7.49; N, 4.17%.
Dichlorido-(N,N-diethyl-1-ferrocenyl-3-thiabutanamine)pal- SCALE3 ABSPACK [1]. Crystal structure was solved by direct
ladium(II) (6). 331 mg (1 mmol) of 5 in 15 mL of chloroform and methods, using SIR2002 (ref. 26) and rened using SHELXL97
H
25
6
soware with multi-scan absorption corrections applied using
28
3
26 mg (1 mmol) of potassium tetrachloridopalladate(II) in 15 (ref. 27) program both incorporated in WinGX program
mL of water were mixed and irradiated in an ultrasonic bath for package. All non-H atoms were rened anisotropically to
0 min, and then stirred at room temperature overnight. The convergence. The contribution of the hydrogen atoms, in their
3
color of the water layer changed from light brown to almost calculated positions, was included in the renement using a
colorless. The organic layer was dried overnight (anhydrous riding model. A summary of crystallographic data is given in
Na SO ), chloroform evaporated and the residue dissolved in 15 Table S3.† Selected bond lengths and bond angles are given in
2 4
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Table S4.† gures were produced using ORTEP-3 (ref. 29) and
519; (d) A. Suzuki, in Metal-Catalyzed Cross-Coupling
Reactions, ed. F. Diederich and P. J. Stang, Wiley-VCH, New
York, 1998, pp. 49–97.
30
MERCURY, Version 2.4. The soware used for the preparation
28
31
32
of the materials for publication: WinGX, PLATON, PARST.
Dichlorido-(N,N-diethyl-1-ferrocenyl-3-thiabutanamine)pal-
ladium(II) (6), polymorph II. Single-crystal X-ray diffraction data
for polymorph II (Fig. S5†) were collected and treated in the
same way as it is described for polymorph I in the previous
section. Since complex 6 in polymorph II crystallizes in the
9 (a) N. Miyaura and A. Suzuki, Chem. Rev., 1995, 95, 2457–
2483; (b) A. Suzuki, J. Organomet. Chem., 1999, 576, 147–
168; (c) E. J.-G. Anctil and V. Snieckus, J. Organomet. Chem.,
2002, 653, 150–160; (d) S. Kotha, K. Lahiri and
D. Kashinath, Tetrahedron, 2002, 58, 9633–9695.
space group Pna2
1
and racemic twinning is present in its crystal 10 T. J. Colacot, Platinum Met. Rev., 2001, 45, 22–30.
structure, the Flack x parameter was rened by means of TWIN 11 Phosphorus(III) Ligands in Homogeneous Catalysis: Design and
29
and BASF to yield 0.43. A summary of crystallographic data is
Synthesis, ed. P. C. J. Kamer and P. W. N. M. van Leeuwen,
given in Table S5.† Selected bond lengths and bond angles are
John Wiley, New York, 2012.
given in Table S6.† The main conformational difference of the 12 (a) R. D. Vuki ´c evi ´c , M. Vuki ´c evi ´c , Z. Ratkovi ´c and
Pd complex in two polymorphs is the mutual orientation of
ethyl groups bonded to the N1 atom (Fig. S7†). Dihedral angle
S. Konstantinovi ´c , Synlett, 1998, 1329–1330; (b)
M. D. Vuki ´c evi ´c , Z. R. Ratkovi ´c , A. T. Teodorovi ´c ,
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9001–9006.
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ꢀ
1
2.0(5) and 78(1) in polymorphs I and II, respectively.
1
3 D. Ili ´c , I. Damljanovi ´c , D. Stevanovi ´c , M. Vuki ´c evi ´c ,
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