A novel iron complex for cross-coupling reactions of multiple C-Cl bonds in polychlorinated solvents with grignard reagents

Article abstract of DOI:10.1007/s10562-012-0913-2

A novel iron(III) complex (2) of a pincer ligand [1, N2,N6-bis(2,6- diisopropylphenyl)pyridine-2,6-dicarboxamide] was developed and used for remediation of polychlorinated solvents via sp3-sp3 coupling of Grignard reagents with C-Cl bonds. The use of an iron catalyst for such coupling reactions is highly desirable due to its greener and more economical nature. Complex 2 was characterized using various spectroscopic techniques: electrospray ionization mass spectrometer (ESI-MS, m/z 575.1), cyclic voltammetry (E _1/2, 0.03 V and ΔE, 0.97 V), and ultraviolet visible (UV/Vis) spectroscopic techniques. The iron(III) complex showed efficient activation of multiple C-Cl bonds and catalyzing C-C coupling of polychlorinated alkyl halides, such as dichloromethane (CH₂Cl₂), chloroform (CHCl₃), and carbon tetrachloride (CCl₄), with various Grignard reagents under ambient reaction conditions. Complex 2 showed exceptional activity with reactions approaching near completion in about 5 min. With the required catalyst loading as low as 0.2 mol%, considerably high turnover numbers (TON = 483) and turnover frequency (TOF = 5,800 h^-1) were obtained. None of the products detected during the reaction contained any chlorine, indicating an efficient dechlorination method while synthesizing products of synthetic and commercial interest. Interestingly, the catalyst was capable of replacing all chlorine atoms in each polychlorinated solvent under the investigations with high conversion. Springer Science+Business Media, LLC 2012.

Full text of DOI:10.1007/s10562-012-0913-2

Catal Lett (2012) 142:1397–1404
DOI 10.1007/s10562-012-0913-2
A Novel Iron Complex for Cross-Coupling Reactions of Multiple
C–Cl Bonds in Polychlorinated Solvents with Grignard Reagents
•
Yashraj Gartia Sharon Pulla Punnamchandar Ramidi
•
•
•
Carolina Costa Farris Zeid Nima Darin E. Jones
•
•
•
Alexandru S. Biris Anindya Ghosh
Received: 18 July 2012 / Accepted: 21 September 2012 / Published online: 9 October 2012
Ó Springer Science+Business Media New York 2012
Abstract A novel iron(III) complex (2) of a pincer ligand
[1, N2,N6-bis(2,6-diisopropylphenyl)pyridine-2,6-dicarb-
oxamide] was developed and used for remediation of
polychlorinated solvents via sp3–sp3 coupling of Grignard
reagents with C–Cl bonds. The use of an iron catalyst for
such coupling reactions is highly desirable due to its
greener and more economical nature. Complex 2 was
characterized using various spectroscopic techniques:
electrospray ionization mass spectrometer (ESI-MS, m/z 575.1),
cyclic voltammetry (E1/2, 0.03 V and DE, 0.97 V), and
ultraviolet visible (UV/Vis) spectroscopic techniques. The
iron(III) complex showed efficient activation of multiple
C–Cl bonds and catalyzing C–C coupling of polychlori-
nated alkyl halides, such as dichloromethane (CH2Cl2),
chloroform (CHCl3), and carbon tetrachloride (CCl4), with
various Grignard reagents under ambient reaction condi-
tions. Complex 2 showed exceptional activity with reac-
tions approaching near completion in about 5 min. With
the required catalyst loading as low as 0.2 mol%, consid-
erably high turnover numbers (TON = 483) and turnover
frequency (TOF = 5,800 h-1) were obtained. None of the
products detected during the reaction contained any chlo-
rine, indicating an efficient dechlorination method while
synthesizing products of synthetic and commercial interest.
Interestingly, the catalyst was capable of replacing all
chlorine atoms in each polychlorinated solvent under the
investigations with high conversion.
Keywords Pincer complex ꢀ C–C coupling ꢀ
Catalyst design ꢀ Cross-coupling ꢀ Iron
1 Introduction
Large quantities of chlorinated organic molecules, espe-
cially polychlorinated alkanes continue to be broadly used
in various industrial and research applications. In the light
of growing concerns about the disposal of the chlorinated
organic molecules, their use as synthetic feedstock can
provide a valuable alternative to the traditional disposal
while enabling the synthesis of high value chemical prod-
ucts. One promising approach in using the chlorinated
solvents as feedstock is to catalytically couple the solvents
with Grignard reagents.
Alexandru S. Biris and Anindya Ghosh contributed equally to this
manuscript.
Electronic supplementary material The online version of this
article (doi:10.1007/s10562-012-0913-2) contains supplementary
material, which is available to authorized users.
C–C coupling of organometallic reagents and organic
electrophiles using transition metal catalysts has evolved
into a significant area of research in synthetic chemistry
[1, 2]. Within this area, a progression in the transition-
metal-catalyzed cross coupling of activated aryl and alke-
nyl halides with organometallic nucleophiles has been
observed due to their general applicability, ready avail-
ability and high selectivity [3]. While various nickel [4–19]
and palladium [20, 21] catalysts have been studied for
Kumada-Corriu coupling of Grignard reagents with acti-
vated aryl and alkenyl halides, not many studies have been
Y. Gartia ꢀ S. Pulla ꢀ P. Ramidi ꢀ C. C. Farris ꢀ
D. E. Jones ꢀ A. Ghosh (&)
Department of Chemistry, University of Arkansas at Little Rock,
2801 South University Avenue, Little Rock, AR 72204, USA
e-mail: axghosh@ualr.edu
Z. Nima ꢀ A. S. Biris
Center for Integrative Nanotechnology Sciences, University
of Arkansas at Little Rock, 2801 South University Avenue, Little
Rock, AR 72204, USA
123

1398
Y. Gartia et al.
reported concerning the cross-coupling of Grignard
reagents with unactivated alkyl halides. One impediment in
this pursuit may be the complexity of alkyl halides, espe-
cially those with b-hydrogen atoms. Moreover, their
inability to undergo oxidative addition and participation in
side reactions are other limitations for the selective cross-
coupling of alkyl halides.
O
O
O
O
N
N
NH
N
HN
Fe
Cl
N
1
2
Even though there have been attempts to activate mul-
tiple C–Cl bonds in a carbon center of a polychloroalkane,
only a few have proved promising. Activation of the C–Cl
bonds has been reported in the presence of Ag-complex
[22] and a P,N-ligand coordinated RhI complex [23].
However, the products formed as a result of these C–Cl
activations did not result in any multiple C–C bond for-
mations. To the best of our knowledge, only two groups
have reported the coupling of multiple C–Cl bonds of di or
polychloroalkanes with Grignard reagents to form C–C
bonds via sp3–sp3 coupling [24, 25]. Ni-pincer catalyst was
reported for an efficient and highly selective activation of
multiple C–Cl bonds in CH2Cl2 and CHCl3 [24] and other
polychlorinated alkanes [26]. The use of these metals has
its own limitations. A few disadvantages associated with
previous studies include high costs, toxicity, harsh reaction
conditions, and low conversions of the substrates. These
issues require us to look for greener and more economic
alternatives.
Fig. 1 N2,N6-bis(2,6-diisopropylphenyl)pyridine-2,6-dicarboxamide
(1) and its iron complex (2)
the present study, we likewise used a diamidopyridine
based N,N,N pincer ligand. The synthesis and use of the
ligand [1, N2,N6-bis(2,6-diisopropylphenyl)pyridine-2,6-
dicarboxamide] (Fig. 1) has been reported previously [45].
The authors reported synthesis and characterizations of Ru
and Ni complexes using a deprotonated form of the ligand
for ring closing metathesis. The nickel complexes of this
ligand and analogous ligands have also been reported for
reaction with carbon dioxide and other ligands [46, 47].
The iron(III) complex (2) (Fig. 1) of the ligand, however,
was not reported. This is the first time the iron(III) complex
of this ligand has been synthesized and put under investi-
gation for its catalytic activity.
In this report, we discuss the iron (III) complex (2)
catalyzed cross-coupling of polychlorinated solvents, such
as CH2Cl2, CHCl3, CCl4, with Grignard reagents
(Scheme 1). Catalyst 2 was able to activate multiple C–Cl
bonds leading to various cross-coupled products. In this
manner, polychlorinated solvents can be turned into less
toxic and high value-added molecules. No special condi-
tions or special equipment were required and reactions
could be performed at room temperature with an inert
atmosphere provided by nitrogen. The catalyst (2) showed
unprecedented activity with reactions completed in 5 min.
A turnover number (TON) and turnover frequency (TOF)
as high as 483 and 5,800 h-1, respectively, with a catalyst
loading of only 0.2 mol% was obtained for the reaction.
While reacting CH2Cl2 with Grignard reagent, iron(III)
catalyst (2) showed a TOF of 3,780 h-1 which is 40–80
times higher than the previous reports of CH2Cl2 coupling
with Grignard reagent using FeCl3, Fe(acac)3, and the Fe
complex of an amine-bis(phenolate) ligand [25]. It is also
40 times more efficient than the most active catalyst, a Ni
complex of a pincer NN2 ligand, reported previously [24].
Furthermore, previous studies required special reaction
conditions, such as high temperature (100 °C or so),
microwave irradiation [25], or conducting reactions at
temperatures below 0 °C [24]. This is the first such report
of a novel iron complex synthesized and studied exten-
sively for the activation of multiple C–Cl bonds in different
polychlorinated solvents.
Recently, the development of new iron complexes for
coupling reactions has gained much interest owing to the
fact that they are environmentally benign and less costly.
Having been first reported by Kochi [27, 28] in 1971, this
research opportunity has not been exploited until recently.
Among the reports on the use of iron catalyst for the cross
coupling of Grignard reagent with activated alkyl halides
and sp3–sp3 coupling with unactivated alkyl halides [29–
41], only a few studies on the activation of C–Cl bond have
been reported [42, 43]. The activation of multiple C–Cl
bonds in polychlorinated compounds has not been studied
extensively using an iron catalyst. Thus far, only one study
of the multiple C–Cl activation of CH2Cl2 has been
reported [25] using iron catalysts. The use of iron-based
catalysts for multiple C–Cl bonds activation and their
subsequent coupling with Grignard reagents is a field
which has largely remained unexplored and thus provides
the motivation for the present work.
Their unique electronic and structural properties, along
with ease of synthesis and ready availability of starting
materials, renders the use of pincer complexes for catalysis
an effective and economic approach. Pd and Ni complexes
of pincer ligands have been found to be efficient catalysts
for Kumada coupling [24]. Further reports using metal
complexes of amido-based pincer ligands for the C–C
coupling have described the high activity of N,N,P- and
N,N,N chelating ligands over P,N,P pincer ligands [44]. In
123

A Novel Iron Complex for Cross-Coupling Reactions of Multiple C–Cl Bonds
1399
H
C
2.2 Synthesis of 1 and 2
H
C
2
CH2Cl2
R'
C CH2
,
H3C
R
R
R
,
H
RMgX
25 oC , N2
H
H
Major product
1 was synthesized according to the literature procedure
with slight modifications [45]. 1 was deprotonated with
n-butyllithium in THF and reacted with anhydrous ferric
chloride (FeCl3) to obtain 2. Detailed synthetic methods of
1 and 2 are described in the Supporting information.
(b)
(a')
(b')
R = CH2-R'
H
H
2
CHCl3
CCl4
,
R
R
R
CH3
(a)
,
R
C
H
R
C
R
RMgX
25 oC , N2
R
(b)
(c)
2.3 Cross-Coupling of CH2Cl2 with Butylmagnesium
Chloride
R
H
C
H
H
C
2
CH3
,
R
,
,
R
R
R
R
R
C
RMgX
25 oC , N2
R
R
Cross-coupling reactions were performed according to the
following general method. Catalyst 2 (0.5 mg, 0.87 lmol)
in 0.5 mL THF was taken in a 5 mL round bottom flask
(purged with N2), and to this solution 2 M n-butylmagne-
sium chloride solution in THF (0.42 mL, 0.84 mmol) was
added. To the reaction mixture (27 lL, 0.42 mmol) of
CH2Cl2 in 2 mL THF was added slowly using a syringe
pump at the rate of 24 mL/h. After 5 min, the reaction was
completely stopped by destroying the excess Grignard
reagent using methanol, and the reaction products were
analyzed using GC–MS technique. An internal standard
decane was used to quantify the product formed.
(a)
(b)
(c)
(d)
Scheme 1 General scheme for products formed in the cross coupling
reaction of CH2Cl2, CHCl3 and CCl4 with Grignard reagents
2 Experimental
2.1 Materials and Methods
All of the chemicals and solvents were obtained either
from Aldrich Chemical Co., USA, or Fisher Scientific
Company, USA, and used as-obtained without further
purification unless otherwise stated. Tetrahydrofuran
(THF), acetonitrile, hexanes, toluene, chloroform, and
carbon tetrachloride were purified according to procedures
described in the literature [48]. Anhydrous dichlorometh-
ane was purchased from Aldrich Chemical Co., USA, and
used without further purification. CCl4 was used in very
small quantity and very cautiously as per regulations.
2.4 Cross Coupling of CHCl3 and CCl4 with Grignard
Reagent
Catalyst 2 (0.5 mg, 0.87 lmol) in 0.5 mL THF was taken
in a 5 mL round bottom flask (purged with N2), and to this
solution 2 M n-butylmagnesium chloride in THF
(0.63 mL, 1.26 mmol) was added. To the reaction mixture,
CHCl3 (34 lL, 0.42 mmol) was added. In case of reaction
with CCl4 (40 lL, 0.42 mmol), 1.68 mmol of Grignard
reagent was added. After 5 min, the reaction was stopped
by destroying the excess Grignard reagent using methanol,
and the reaction products were analyzed using GC–MS
technique. An internal standard decane was used to quan-
tify the product formed. All reactions were performed in
duplicate to check for the reproducibility of the reactions.
1H-NMR spectra were obtained using
a Bru¨ker
600 MHz nuclear magnetic resonance (NMR) instrument.
The spectra were collected at 25 °C, and chemical shifts
are in ppm (d) relative to tetramethylsilane (TMS) as an
external standard unless otherwise stated. Infrared spectra
were obtained on a Shimadzu FT-IR Affinity-1 spectro-
photometer. Electrospray ionization mass spectra (ESI-
MS) were obtained using an Agilent 100 series MSD VL
spectrometer. gas chromatography–mass spectrometry
(GC–MS) were obtained using an Agilent technologies
6890N network GC system and equipped with Agilent
Technologies 5975 inert XL mass selective detector.
Ultraviolet–visible spectra (UV–Vis) were recorded using
a Varian Cary 5000 UV–Vis–NIR spectrophotometer.
Elemental analysis was performed at the Midwest Mi-
crolab, LLC, Indianapolis, USA. Cyclic voltammetry was
conducted using Pine Bipotentiostat and following a
conventional three-electrode method. An Ag/AgCl ref-
erence electrode was used for the measurement.
3 Results and Discussion
With slight modifications made to the previously reported
method [45], the ligand was synthesized in two steps. An
acid chloride of 2,6-pyridinedicarboxylic acid was obtained
which was finally reacted with 2,6-diisopropyl aniline in
the presence of triethylamine to obtain the desired ligand.
Pure white crystalline ligand was obtained by crystalliza-
tion from hot ethanol solution. Detailed synthesis of the
ligand is described in the Supporting information (Fig. S1).
123

1400
Y. Gartia et al.
The ligand was characterized using various spectroscopic
1
techniques. H-NMR of the ligand showed the character-
complex; thus, we formulated the square-planar structure
of the complex. The presence of Cl was further checked by
dissolving the complex in acetonitrile and then adding
silver nitrate which yielded stoichiometric precipitate of
chloride. The complex is also miscible in low polarity
solvents, such as benzene, toluene, and ether, indicating
that it is a charge neutral species. The UV–Vis spectrum of
the iron complex in THF shows a major peak at 364 nm
which eventually tails to the visible region giving rise to
the yellowish color in the solution (Fig. S10, Supporting
information). The cyclic voltammetry (Fig. S4, Supporting
information) of the iron complex shows a quasi-reversible
peak with E1/2 of 0.03 V and DEp of 0.97 V with respect to
an Ag/AgCl reference electrode. FT-IR shows a peak at
around 1,620 cm-1, corresponding to the amide peak of the
complex. Repeated attempts were made to grow the crys-
tals of the iron complex. However, we have been unsuc-
cessful in growing diffraction quality crystals.
istic peaks at 1.29 ppm (isopropyl CH3, d) and 3.25 ppm
(isopropyl CH, m). The presence of the amide (9.11 ppm)
and aromatic hydrogens was also observed at the expected
positions confirming the formation of the ligand (Fig. S2,
Supporting information). 13C-NMR spectrum of the ligand
also confirms the formation of the ligand (Fig. S2, inset).
ESI-MS of the ligand (Fig. S3, Supporting information) in
negative ion mode showed a peak at m/z 484.5 (M-H)
which was in agreement with the formulation of the ligand.
The Fourier transform infrared spectroscopic (FT-IR)
analysis showed the characteristic carbonyl stretching
corresponding to the amide bonds at 1,660 cm-1 and NH
stretching at 3,363 and 3,287 cm-1 further confirming the
formation of the ligand.
The iron(III) complex (2) of the ligand was synthesized
according to the scheme shown in Fig. S1 (Supporting
information). Synthesis of 2 was performed in THF under
nitrogen atmosphere. A strong base (n-butyllithium) was
used to deprotonate the amide protons; reaction of the
deprotonated ligand with anhydrous FeCl3 yielded a dark
red complex (2). We believe that the iron coordinates with
the deprotonated amide of the ligand to form complex 2
(Fig. 1). However, a different kind of coordination between
metal and ligand was reported in the crystal structures of
the ruthenium complexes of 1 [45]. Hence, coordination of
iron with the oxygen of the amide group is another possi-
bility that cannot be refuted. The higher coordination
number is also not unlikely in this case. The complex was
further characterized using ESI-MS (m/z 575.1; Fig. 2).
The inset of Fig. 2 shows the theoretical simulation of the
mass spectrum following the formula of complex 2. The
ESI-MS shows the incorporation of a Cl atom into the
The cross-coupling reaction of CH2Cl2 with butylmag-
nesium chloride was performed for preliminary screening
of the catalyst activity. Catalyst 2 was taken in a 5 mL
round bottom flask (purged with N2), and 2 M of butyl-
magnesium chloride solution in THF was added to it. To
the solution, CH2Cl2 dissolved in 2 mL THF was added
slowly using a syringe pump at the rate of 24 mL/h (see
‘‘Experimental’’). The samples were taken for analysis
after 5 min at the end of the slow addition. Reaction
products were analyzed using GC–MS technique. An
internal standard (Decane) was used to quantify the product
formed.
Three products were formed in the cross-coupling of
CH2Cl2 with butylmagnesium chloride using 2 (Scheme 1).
A cross-coupling product of one butyl group by activation
of one C–Cl bond, which eventually on elimination yielded
pentene, was detected in significant amount during the
reaction. However, it is also possible that the iron center in
complex 2 was reduced by the Grignard reagents [14].
Thus, chloropentane, which is first produced by reaction of
one Cl atom of CH2Cl2 with butylmagnesium chloride,
may oxidatively add to the reduced iron center and, on
further b-H elimination, yield pentene. Nonane is also
formed in a significant quantity by the cross-coupling of
two butyl groups with the two C–Cl bonds of CH2Cl2.
Another product detected during the reaction was hexane,
which may be due to the coupling of chloro pentane with
another CH2Cl2 and then further dechlorination. It was
observed that the products at the end of the reaction were
dechlorinated alkanes or alkenes. The iron complex may
form a hydride intermediate by virtue of b-H elimination of
the Grignard reagent which could further assist in the
dechlorination process. In addition to the Grignard reagent,
the solvent THF may act as a source of hydrogen in a
similar fashion facilitating the replacement of all of the Cl
Fig. 2 Electrospray ionization mass spectrum (ESI-MS) of the iron
complex (negative ion mode, m/z) and its theoretical isotope
distribution (inset)
123

A Novel Iron Complex for Cross-Coupling Reactions of Multiple C–Cl Bonds
1401
Table 1 TON and TOF of different substrate to catalyst ratio
reactions
Entry
Catalyst 2 (mol%)
Yield (%)
TON
TOF (h-1
)
1
2
3
4
0.8
0.4
0.2
0.04
100
89.4
54.5
13
125
218
263
315
1,500
2,616
3,160
3,780
CH2Cl2 (27 lL, 0.42 mmol), butylmagnesium chloride 2 M in THF
(0.42 mL, 0.84 mmol) at room temperature and slow addition of
CH2Cl2 over 5 min. Yield (%) is the total % of CH2Cl2 cross coupled
Fig. 4 Effect of ratio of CH2Cl2 to butylmagnesium chloride on the
cross coupling reactions. CH2Cl2 (27 lL, 0.42 mmol), at room
temperature and reaction time 5 min. ‘‘Dichloromethane’’ is unre-
acted CH2Cl2
atoms with hydrogen in the products. Further investigation
will be required to understand the mechanistic pathways in
detail.
Various reactions were next carried out in order to
understand the effect of various reaction parameters: cat-
alyst to substrate ratio, the effect of temperature, and the
equivalence of Grignard reagent to the substrate (CH2Cl2).
Reactions were carried out using varying amounts of cat-
alyst to CH2Cl2 ratios. Almost all of the CH2Cl2 cross-
coupled when 0.4 mol% of the catalyst was used (Table 1).
A further increase in the catalyst concentration to
0.8 mol% leads to the completion of the reaction and to a
decrease in the overall TON to 125. The highest TON of
315 was observed using 0.04 mol% catalyst, though the
percentage of CH2Cl2 coupled was only 13 %. Use of
0.2 mol% catalyst increased the yield to 54.5 % with a
relatively high TON of 263. Interestingly, a higher TON
was observed when less of the catalyst was used. This may
be due to the fact that, when a large amount of catalyst was
employed, the homo-coupling reaction of the Grignard
reagent increased, thus reducing the overall TON and TOF
of the desired hetero-coupling reaction.
Reactions were also carried out at different temperatures
in order to understand the effect of temperature on the
cross-coupling. Reactions were performed following the
procedure described above but at temperatures ranging
from -15 to 70 °C. It was observed that, with increasing
temperatures, more products formed. During the reaction,
an increase in TON from 203 at -15 °C to 364 at 70 °C
was obtained. As shown in Fig. 3, the percent of CH2Cl2
coupled is highest at 70 °C with the formation of pentene,
hexane, and nonane increasing with the increase in tem-
perature. Further studies were conducted at room temper-
ature. We found that the catalyst was highly active at room
temperature, with a percentage yield and TON of 54.5 %
and 263, respectively.
As shown in Fig. 4, an increase in the concentration of
the Grignard reagent (butylmagnesium chloride) also leads
to an increased reaction rate and increased yield of product.
Experiments were performed using different CH2Cl2 to
Grignard reagent ratios ranging from 1:1 to 1:12. As
revealed by Fig. 4, with the increase in the amount of
Grignard reagent, the percentage of CH2Cl2 coupled
increased. Almost all of the CH2Cl2 was found to be
consumed when 12 equivalents of the Grignard reagent was
used indicating that use of excess Grignard reagent
increased the cross-coupled products. The TON of the
reaction increased from a mere 190 to 482 as the ratio of
CH2Cl2 to Grignard reagent was increased from 1:1 to
1:12. However, a larger amount of undesirable homo-
coupled product was also detected when excess Grignard
reagent was used. On the other hand, using just two
equivalents of Grignard reagent still resulted in a signifi-
cant amount of conversion with minimal side products. As
a result, we decided to carry out the remainder of the
reactions keeping a CH2Cl2 to Grignard reagent ratio of
1:2.
Fig. 3 Effect of temperature (-15 to 70 °C) on the coupling of
butylmagnesium chloride with CH2Cl2. CH2Cl2 (27 lL, 0.42 mmol),
n-butylmagnesium chloride 2 M in THF (0.42 mL, 0.84 mmol),
reaction time 5 min. ‘‘Dichloromethane’’ is unreacted CH2Cl2
Cross-coupling of CH2Cl2 with various Grignard
reagents was also performed. Scheme 1 shows the major
cross-coupling products formed on the reaction of CH2Cl2
123

1402
Y. Gartia et al.
Table 2 Cross coupling of CH2Cl2, CHCl3 and CCl4 with various Grignard reagents
Grignard reagent
CH2Cl2
a0
CHCl3
a
CCl4
a
b
b0
%
b
c
%
b
c
d
%
1
2
3
29.7
84
5.4
–
19.4
54.5
27.9
1.6
37
50.9
21.1
99.9
–
22
61
14
97
MgCl
MgCl
–
99.5
81.5
72
35
12.6
26.7
86.2
98.7
16
22.5
30.7
60.6
38.2
14.1
–
–
85.9
97.2
48
10.9
17.2
MgCl
5
4
5
49.6
41.4
5.6
3
–
55.3
69.2
54.6
23
19
5.5
1.2
99.1
99.8
29.1
14.1
45.3
56
7.6
–
–
82
94
MgCl
16.7
75.6
22.9
MgCl
7
6
40.2
–
5.4
55.9
67
17.6
3.5
5.4
80
34.8
22.7
11.6
72
69.1
MgCl
7
9.4a
29.5
–
39.7
Trace
96.4
99.9
Trace
24.1
–
86.1
MgCl
8
9
53.1
22.4
17.6
8.9
22.8
98
12.6
6.3
46
36.6
30.4
95.2
92.3
17.9
30
56
11
–
–
84.9
77.6
MgCl
6
71.4
55.6
18.1
29.5
MgCl
10
28.8
5
17
57.8
36.3
52
11.5
99.8
15.3
37.5
42
94.8
MgCl
Reactions in THF using 2 (0.5 mg, 0.87 lmol), CH2Cl2, CHCl3 and CCl4 (0.42 mmol) and Grignard reagent (1 equivalent to the number of C–Cl
bonds) at room temperature. Samples were analyzed after 5 min of the reaction
a0 = Single C–Cl bonds of CH2Cl2 coupled with the Grignard reagent
b0 = One C–Cl bond of CH2Cl2 coupled with Grignard reagent and one C–Cl bond coupled with another CH2Cl2 molecule
a, b, c and d = mono, di, tri and tetra substituted coupled products
% is the total percentage of the substrate coupled
a
The product is toluene, which is ‘a’ type product instead of the ‘a0’ type product
with a Grignard reagent. Table 2 shows the percentage of
different major cross-coupling products formed along with
the total CH2Cl2 coupled. For the cross-coupling reaction
with phenylmagnesium chloride (entry 7; Table 2), 39.7 %
of total CH2Cl2 coupled; 29.5 % of the product was ‘b’
type product, a result of the activation of both C–Cl bonds.
Use of phenethylmagnesium chloride resulted in 17.6 %
phenethyl di-substituted products (entry 8; Table 2) with a
98 % conversion of CH2Cl2. When benzylmagnesium
chloride (entry 9; Table 2) was used, additional coupling
product—other than those shown in the Scheme 1—was
observed. Apart from obtaining 1,3-diphenylpropane
(Ph–(CH2)3–Ph), 1,4-diphenylbutane (Ph–(CH2)4–Ph) was
also observed in good amount during the reaction. Similar
product was also observed in earlier reports by another
research group when Fe(acac)3 was used as the catalyst
[25]. The use of ethylmagnesium chloride (entry 2;
Table 2) showed predominantly ‘a0’ type, single C–Cl
activated product. Double C–Cl substituted products like
pentane, as described in the Scheme 1, were not observed.
Similarly, primarily single C–Cl activated products were
observed while using cyclopentylmagnesium chloride
(entry 6; Table 2). As shown in Table 2, 40.2 % out of the
total 55.9 % CH2Cl2 (entry 6) coupled were singly coupled
123

A Novel Iron Complex for Cross-Coupling Reactions of Multiple C–Cl Bonds
1403
products. Coupling of both C–Cl bonds with the cyclo-
pentylmagnesium chloride (entry 6; Table 2) was not
observed at all. It was also observed that, similar to the
cyclopentylmagnesium chloride, all of the alkyl and allyl
Grignard reagents primarily gave monosubstituted prod-
ucts. As seen in Table 2, hexylmagnesium chloride (entry
3), octylmagnesium chloride (entry 5) and allylmagnesium
chloride (entry 4) yielded 48, 41.4, and 49.6 percentages of
monosubstituted products, respectively. When using eth-
ylmagnesium chloride (entry 2; Table 2), 84 % of mono-
substituted product was produced primarily due to
activation of only one C–Cl bond in CH2Cl2.
all-carbon quaternary centers, such as the ‘d’ type products
(Scheme 1) mentioned above, is synthetically challenging
due to the steric repulsion of the carbon substituents, as
well as the number of degrees of freedom that are acces-
sible from the acyclic precursors [49–52]. However, 2 is
capable of forming quaternary substituted alkanes in the
cross-coupling reaction indicating the high efficiency of the
catalyst. Better substitution of multiple C–Cl bonds, espe-
cially in reactions with CH2Cl2 and CHCl3, were observed
with the use of Grignard reagents with bulkier aromatic
groups, such as phenyl, benzyl, and phenethyl groups.
Entry 1 in Table 2 shows the cross-coupling reaction yields
of CH2Cl2, CHCl3, and CCl4 with butylmagnesium chlo-
ride at room temperature. The results indicate that using
0.2 mol% of 2, 54.5 % of CH2Cl2, 99.9 % CHCl3, and
97 % of CCl4, respectively, could be cross-coupled with
butylmagnesium chloride within 5 min. The TONs for
these reactions were found to be 263, 483, and 467 for
CH2Cl2, CHCl3, and CCl4, respectively. The results are
evidence of the high reactivity of the catalyst (2).
Cross-coupling of some other chlorinated solvents was
also carried out using various Grignard reagents at room
temperature. Almost all of the CHCl3 was coupled up with
butylmagnesium chloride within 5 min of the reaction time.
A high TON of 483 was obtained for the reaction involving
CHCl3. Cross-coupling of phenylmagnesium chloride with
CHCl3 produced 96.4 % of triphenylmethane product as
seen in entry 7 in Table 2. Upon using benzylmagnesium
chloride, 30.4 % of ‘c’ type trisubstituted product, and 55 %
‘b’ type disubstituted products were formed (entry 9;
Table 2). 36.6 % of trisubstituted product was also obtained
(entry 8) when CHCl3 was cross-coupled with phenethyl-
magnesium chloride. Reactions with ethylmagnesium chlo-
ride and octylmagnesium chloride, however, showed
predominantly 2 C–Cl bond activated products. As shown in
entry 2 (Table 1), 72 % of CHCl3 coupled with ethylmag-
nesium chloride to form pentane. Similarly, the reaction with
octyl magnesium chloride primarily gave heptadecane
(75.6 %) as shown in entry 5 in Table 2. Using isopropyl-
magnesium chloride, 52 % of disubstituted and 36.3 % of
monosubstituted product were formed. The reactions with
cyclopentylmagnesium chloride (entry 6) and allylmagne-
sium chloride (entry 4) yielded 67 and 54.6 % of mono-
substituted products, respectively, with only about 5 % of all
3 C–Cl activated products formed in both cases.
The mechanism of the cross-coupling reaction is currently
under investigation. However, we have detected a key spe-
cies which is most likely responsible for the catalytic reac-
tions. Similar intermediates have been previously detected
and postulated for such coupling reactions [24, 25]. The
addition of butylmagnesium chloride to THF solution of 2
changes the color of the solution immediately from yellow to
red-orange. The UV/Vis spectrum indicated the disappear-
ance of a peak of the iron catalyst (2) at 364 nm, and a new
peak at 465 nm appeared indicating generation of a possible
reactive intermediate (Fig. S10, Supporting information).
The intermediate was postulated to be the butyl substitution
of Cl atom in 2. A similar change in color was also observed
upon addition of different other Grignard reagents to the
catalyst solution (Fig. S10, Supporting information). UV/Vis
spectra were found to be similar with a maximum peak at
around 465 nm (Fig. S10). The addition of cyclopentyl-
magnesium chloride, however, shifted the peak to 498 nm
(Fig. S10, Supporting information). Formation of the inter-
mediate was further confirmed by the ESI-MS. The iron
catalyst (2) on interaction with butylmagnesium chloride
forms an alkylated species, and the species was detected by
ESI-MS (m/z, 597.4; Fig. S11). A decrease in the absorbance
of a peak at 465 nm of the 2-butyl complex was observed
upon addition of CH2Cl2 indicating a decrease in the inter-
mediate concentration as the reaction approached comple-
tion (Fig. S12, Supporting information).
Cross-coupling of carbon tetrachloride (CCl4) was also
performed with different Grignard reagents in a similar
fashion (Scheme 1). Most of the reactions resulted in 3 C–
Cl activated products. Reaction with phenylmagnesium
chloride gave 72 % of triphenylmethane (entry 7). Ethyl-
magnesium chloride (entry 2) gave 38.2 % of 3 C–Cl
bonds activated product and 30.7 % of 2 C–Cl activated
product. Most of the alkyl Grignard reagents, such as
hexylmagnesium chloride (entry 3) and octylmagnesium
chloride (entry 5), primarily produced 2-Cl activated
products. Further, cyclopentylmagnesium chloride (entry
6) produced 34.8 % of 1-Cl activated product as the major
product. Interestingly, the reaction of CCl4 with butyl-
magnesium chloride gave 14 % of ‘d’ type (Fig. S9)—the
product derived from substitution of four chlorine atoms
and 61 % of trisubstituted product. The creation of
4 Conclusions
By a simple method, we were able to synthesize a new and
efficient iron(III) catalyst that is capable of activating
123

1404
Y. Gartia et al.
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nometallics 28:3233
multiple C–Cl bonds in CH2Cl2, CHCl3, and CCl4 leading
to their cross-coupled products with various Grignard
reagents. By this method, we efficiently converted toxic
polychlorinated solvents into benign and value-added
products. These reactions were performed at ambient
temperature and under an inert atmosphere. The reaction
time was in minutes, with most of the chlorinated mole-
cules coupled with the Grignard reagent in as few as 5 min.
The catalyst was found to be highly active and showed a
TON and TOF as high as 483 and 5,800 h-1, respectively,
during the coupling reaction of CHCl3 with Grignard
reagent. The required catalyst loading for all of the reac-
tions was low, only 0.2 mol%. An increase in temperature
and the amount of the Grignard reagent led to an increase
in the cross-coupling products. However, a change in these
parameters for increasing the selectivity toward any par-
ticular product was not observed. Use of bulkier aromatic
Grignard reagents was found to be more selective towards
multiple C–Cl bonds activation. For example, phenyl-
magnesium chloride formed the most multiple C–Cl acti-
vated products. In the case of CH2Cl2, *29.5 % of 2 C–Cl
activated product was formed. On the other hand, in the
case of CHCl3 and CCl4, respectively, 96.4 and 72 % of 3
C–Cl activated products were observed. The mechanistic
details, scope, and utility of the catalytic applications are
currently under further investigation. Additional applica-
tions of the catalyst for different coupling reactions and
other chemical transformations are also under
investigation.
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Acknowledgments AG would like to thank NSF EPSCoR (NSF/
EPS-1003970) and Department of Energy (DE-FG3606G086072) for
financial support to complete the research work. The editorial assis-
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