Application of bisphosphomide-palladium(II) pincer complex in Suzuki-Miyaura cross-coupling reaction under microwave irradiation

Article abstract of DOI:10.1007/s12039-014-0594-z

The bisphosphomide-based pincer complex [PdBr{2,6-{ Ph₂PC(O)} ₂(C₆H₃)}] (2) has shown very high catalytic activity in Suzuki-Miyaura cross coupling reaction under microwave irradiation for a variety of aryl bromides and aryl boronic acids. The complex showed the same efficiency for gram scale reactions.

Full text of DOI:10.1007/s12039-014-0594-z

c
J. Chem. Sci. Vol. 126, No. 3, May 2014, pp. 711–716. ꢀ Indian Academy of Sciences.
Application of bisphosphomide-palladium(II) pincer complex
in Suzuki–Miyaura cross-coupling reaction under microwave
irradiation
MARUTHAI KUMARAVEL, PAWAN KUMAR and MARAVANJI S BALAKRISHNA∗
Phosphorus Laboratory, Department of Chemistry, Indian Institute of Technology Bombay, Powai,
Mumbai 400 076, India
e-mail: krishna@chem.iitb.ac.in
MS received 13 September 2013; revised 20 November 2013; accepted 20 November 2013
Abstract. The bisphosphomide-based pincer complex [PdBr{2,6-{Ph2PC(O)}2(C6H3)}] (2) has shown very
high catalytic activity in Suzuki–Miyaura cross coupling reaction under microwave irradiation for a variety of
aryl bromides and aryl boronic acids. The complex showed the same efficiency for gram scale reactions.
Keywords. Pincer complex; bisphosphomide; Suzuki–Miyaura coupling; microwave irradiation;
palladium(II).
1. Introduction
reactions of aryl and heteroaryl halides (figure 1). To the
best of our knowledge, this is the first report of a pin-
cer complex employed in microwave-assisted catalytic
reactions.
The recent focus of interest on pincer complexes is due
to their extended utility in the field of homogeneous
catalysis.1 Pincer complexes offer interesting possibili-
ties both in terms of mechanistic understanding and cat-
alytic performance.1b The high catalytic efficiency is
attributed to the stable and compact geometry of the
pincer complexes with ideal steric and electronic prop-
erties. Among the cross coupling reactions, Suzuki–
Miyaura reaction is more popular because of its func-
tional group tolerance for a wide variety of substrates.2
Microwave-assisted organic synthesis is becoming very
useful and popular method due to its rapid reaction
time, reproducibility and easy scale up methodolo-
gies in research laboratories and also in industrial
processes.3
We recently reported the synthesis of first exam-
ples of bis(phosphine), 1,3-phenylenebis((diphenyl-
phosphino)methanone), {2,6-{Ph2PC(O)}2(C6H3)} (1)
(here after referred as bis(phosphomide)) and its tran-
sition metal chemistry and catalytic utility in hydro-
formylation reactions.4a Bisphosphomide 1 is a mode-
rate σ-donor but a very good π-acceptor. This feature is
ideal for facilitating the reductive elimination step in the
catalytic cycle of cross-coupling reactions.4 As a part of
our interest in designing the novel catalysts for organic
transformations,5 we report here the catalytic utility of
pincer complex, [PdBr{2,6-{Ph2PC(O)}2(C6H3)}] (2)
in microwave-assisted Suzuki–Miyaura cross-coupling
2. Experimental
All bromo compounds and boronic acid derivatives
were purchased from Aldrich. Anhydrous K2CO3 were
purchased from SDFINE Chemicals, and used as
received without further purification. Methanol, dis-
tilled over magnesium cake, was used for all catalytic
reactions. All other reagents were used as received.
The complex 2 was prepared according to literature
procedure.4a Microwave experiments were carried out
using a CEM Discover Labmate-microwave appara-
tus. GC analyses were conducted using an Agilent Gas
Chromatograph 6890 Series, Hewlett Packard equipped
with an HP5-MS capillary column (30 m × 0.25 mm ×
0.25 μm) and an FID detector. All GCMS analyses were
done by Agilent 7890A GC system connected with
5975C inert XL EI/CI MSD (with triple axis detector).
2.1 General procedure for the coupling reaction
A mixture of 4-bromotoluene (0.050 g, 0.291 mmol, 1
eq) and phenylboronic acid (0.043 g, 0.35 mmol, 1.2
eq), 0.2 ml of stock solution prepared from dissolving
palladium complex 2 (0.002 g, 0.1 mol%, 0.001 eq) in
2 mL CH3CN, K2CO3 (0.060 g, 0.436 mmol, 1.5 eq)
and methanol (3 mL) was heated under microwave
∗For correspondence
711

712
Maruthai Kumaravel et al.
were carried out using 4-bromotoluene and phenyl-
boronic acid as a model reaction. The effect of solvents
and the reaction time was optimized using 0.1 mol%
of palladium catalyst and K2CO3 as a base. As summa-
rized in table 1, methanol was chosen as solvent. The
complex 2 gave complete conversion (100%) when the
reaction time was extended to 8 min under microwave
irradiation. Similar results were obtained when the reac-
tion was performed under refluxing temperature (entry
8, 2 h) or at room temperature (entry 9, 12 h). Since
100% yields were obtained in 8 min, microwave condi-
tion was employed. K2CO3 was used as a base due to
its low cost and good efficiency.
To expand the scope of catalytic investigation to
several substrates, complex 2 was tested with highly
challenging ortho-substituted aryl bromides and also
with substrates containing electron donating (deacti-
vating) substituents using phenylboronic acid under
optimized conditions. The results are summarized in
table 2. A very high TOF of ≈7000 was obtained for
methyl and methoxy substituted aryl bromides. Mode-
rate to good conversions were observed for both NMe2
and methoxy substituents at the para position. 2,4-
Dimethoxy-bromobenzene with two methoxy groups
showed a TOF of 4875 (entry 6).
Figure 1. Structure of bisphosphomide based PCP palla-
dium pincer complex 2.
◦
condition at 85 C and 60 watt for 8 mins to give
4-methyl-1,1ꢁ-biphenyl. The substrate scope with dif-
ferent aryl halides and different boronic acids were
tested using the same procedure as above. The typi-
cal molar ratio of the reaction components in all cases
was 1/1.2/1.5/0.001/3 mL (aryl halide, aryl boronic
acid, K2CO3, catalyst and methanol). The conversion
with respect to aryl halide was determined by GC
using dodecane as internal standard and products were
confirmed by GC-MS.
3. Results and discussion
Aryl bromides containing electron withdrawing
(activating) groups at ortho position also showed
almost quantitative conversions (entries 12–14). The
The pincer complex 2 was prepared by using the
recently reported literature method.4a In order to obtain
optimized conditions, initial catalytic investigations
Table 1. Optimization of reaction conditions on Suzuki–Miyaura reaction of
4-bromotoluene with phenylboronic acida.
Br
B(OH)
2
Cat.(2) (0.1mol % Pd)
+
K CO , Solvent,
2
3
MW
Temperature
(deg C)
Time
(min)
Conversionb
(%)
Entry
Solvent
1
2
3
4
5
6
7
8c
9
Methanol
Toluene
THF
CH3CN
Dioxane
DMF
Methanol
Methanol
Methanol
85
110
66
5
5
5
5
5
5
8
2 h
12 h
88
56
3
24
61
55
100
98
94
85
100
130
85
70
RT
aReaction was performed in a sealed tube containing aryl bromides (0.291 mmol),
aryl boronic acid (0.349 mmol; 1.2 eq), base (0.436 mmol; 1.5 eq.), catalyst
(0.1 mol %) and solvent (3 mL). An initial microwave power of 60 W was applied
to reach 85◦C temperature.
bConversions were determined by GC using aryl halides as internal standards.
cConventional heating was carried out using an oil bath

Application of bisphosphomide-palladium(II) pincer complex
713
Table 2. Suzuki–Miyaura reactiona of phenylboronic acid with various aryl halides.
Entry
1
Aryl halide
Product
Conv.(%)b
100
TOF (h−1
7500
)
Br
Br
2
3
88
92
6600
6900
Br
MeO
MeO
MeO
MeO
Br
4
5
6
98
76
65
7350
5700
4875
OMe
OMe
Br
OMe
Br
OMe
MeO
MeO
Br
O
O
7
8
9
98
7350
5550
7500
Me N
Br
Me N
2
2
74
Br
100
Br
10
11
100
99
7500
7425
MeO
MeO
Br
CN
CHO
Cl
CN
Br
12
13
14
100
100
97
7500
7500
7275
CHO
Br
Cl
Br

714
Maruthai Kumaravel et al.
Table 2.
(continued)
Aryl halide
Entry
Product
Conv.(%)b
100
TOF (h−1
7500
)
O
O
Br
Me
Me
15
N
N
Br
Br
16
17
100
98
7500
7350
N
N
S
Br
Br
S
18
100
7500
S
S
19
20
55
90
4125
6750
O N
2
O N
2
Br
a,bReaction conditions are similar to those described in table 1
Table 3. Suzuki–Miyaura reactiona of 4-bromotoluene with various arylboronic acid derivatives.
Entry
Aryl boronic acid
Product
Conv.(%)b
TOF (h−1
)
B(OH)
2
21
98
7350
B(OH)
2
22
23
93
91
6975
6825
OMe
MeO
Cl
B(OH)
2
Cl
B(OH)2
Cl
Cl
Cl
Cl
24
84
6300
B(OH)
2
25
26
27
98
82
93
7350
6150
6975
Cl
Cl
B(OH)
2
CHO
OHC
B(OH)
2

Application of bisphosphomide-palladium(II) pincer complex
(continued)
715
Table 3.
Entry Aryl boronic acid
Product
Conv.(%)b TOF (h−1
)
NO
O N
2
2
B(OH)
2
28
29
30
87
92
70
6525
6900
5250
F
F
B(OH)
2
B(OH)
2
a,bReaction conditions are similar to those described in table 1.
conversions of heteroaromatic bromides such as bro- towards various other organic transformations are under
mopyridines and bromothiophene (entries 16–19) were investigation in our laboratory.
excellent despite their ability to coordinate to the
metal centre and hinder the catalytic process. Fur-
ther, the homo-coupling of phenylboronic acids a very
common and usual side reaction is not observed in all
these cases.
Acknowledgements
We thank the Department of Science and Technology
(DST), New Delhi, for financial support. MK thanks the
Council of Scientific Industrial Research (CSIR), New
Delhi, for Senior Research Fellowship (SRF).
In order to establish the efficiency and versatility of
the precatalyst 2, different aryl boronic acids have been
tested and the results are summarized in table 3. It is
well-known that the boronic acids with electron donat-
ing substituents are more nucleophilic than electron
withdrawing ones and perform better in the coupling
reaction as compared to the later ones. As expected, the
complex 2 catalysed methyl and methoxy substituted
boronic acids efficiently, whereas the relative catalytic
performance with respect to the electron withdrawing
substituents was moderate (entries 25–30) with a TOF
of 6900 for 4-fluorophenylboronic acid.
The actual catalytic performance of a complex is
decided by its effectiveness in scale-up reactions and
its consistent reproducibility. Catalysts which perform
well in large scale reactions are very important for
pharmaceutical and chemical industries. The reaction
between 1 g of p-bromotoluene and 1.2 equivalent
of phenylboronic acid in the presence of complex 2
yielded the coupled product in 78% within 30 min.6
References
1. (a) van der Boom M E and Milstein D 2003 Chem. Rev.
103 1759; (b) Morales-Morales D and Jensen C M (eds)
2007 The chemistry of pincer compounds (Amsterdam:
Elsevier); (c) Morales-Morales D 2008 Mini-Rev. Org.
Chem. 5 141; (d) Selander N and Szabó K J 2011 Chem.
Rev. 111 2048; (e) Beletskaya I P and Cheprakov A V
2004 J. Organomet. Chem. 689 4055
2. (a) Miyaura N and Suzuki A 1995 Chem. Rev. 95 2457;
(b) Bedford R B, Draper S M, Scully P N and Welch S L
2000 New J. Chem. 24 745; (c) Garagorri D B, Bocokic´
V, Mereiter K and Kirchner K 2006 Organometallics 25
3817
3. (a) Sajith A M and Muralidharan A 2012 Tetrahedron
Lett. 53 1036; (b) Hajipour A R, Karami K and Pirisedigh
A 2011 Inorg. Chim. Acta 370 531; (c) Susanto W, Chu C
-Y, Ang W J, Chou T -C, Lo L -C and Lam Y 2012 Green
Chem. 14 77
4. (a) Kumar P, Siddiqui M M, Reddi Y, Mague J T, Sunoj
R B and Balakrishna M S 2013 Dalton Trans. 42 11385;
(b) Gowrisankar S, Federsel C, Neumann H, Ziebart C,
Jackstell R, Spannenberg A and Beller M 2013 Chem.
Sus. Chem. 6, 85; (c) Whittemore S M, Yoder R J and
Stambuli J P 2012 Organometallics 31 6124
4. Conclusions
5. (a) Balakrishna M S, Rao S and Choubey B 2012 J. Chem.
Sci. 124 1191 and references there in; (b) Balakrishna M
S, Suresh D and Mague J T 2011 Inorg. Chim. Acta 372
259; (c) Ganeshamoorthy C, Mague J T and Balakrishna
M S 2008 Eur. J. Inorg. Chem. 596; (d) Ganeshamoorthy
C, Mague J T, Balakrishna M S and Tuononen H M
2008 Inorg. Chem. 47 7035; (e) Venkateshwaran R,
The initial investigations of bisphosphomide-palladium
pincer complex 2 in Suzuki–Miyaura cross-coupling
reaction have been very successful. A very high TOF
was achieved even for sterically hindered and deac-
tivated aryl halides and good yields were obtained
in scale-up reactions. Further utility of this complex

716
Maruthai Kumaravel et al.
Balakrishna M S and Mobin S M 2007 Eur. J. Inorg.
(10 mL) taken in a 25 mL reactor vessel was heated
under microwave condition at 85◦C and 60 watt for 30
min. After the completion of the reaction, the product
(4-methylbiphenyl) obtained was separated and purified
by column chromatography using 5:1 mixture of ethyl
acetate and petroleum ether (b.p. range 60–85◦C). Yield
78% (0.800 g, 4.78 mmol) 1H NMR (400 MHz, CDCl3)δ
7.64 (d, J = 7.1 Hz, 2H), 7.55(d, J = 8.1 Hz, 2H), 7.48
(t, J = 7.5 Hz, 2H), 7.37 (t, J = 7.3 Hz, 1H), 7.30 (d,
J = 7.9 Hz, 2H), 2.45 (s, 3H). Mp. 44–47◦C
Chem. 1930; (f) Punji B, Mague J T and Balakrishna M S
2007 Inorg. Chem. 47 10268; (g) Punji B, Mague J T and
Balakrishna M S 2007 Inorg. Chem. 47 11316; (h) Rao S,
Mague J T and Balakrishna M S 2013 Dalton Trans. 42
11695
6. For large scale reaction: A mixture of 4-bromotoluene
(1.044 g, 6.1 mmol, 1 eq), phenylboronic acid (0.893 g,
7.3 mmol, 1.2 eq), K2CO3 (1.266 g, 9.16 mmol, 1.5 eq),
complex 2 (0.0042 g, 0.1 mol%, 0.001 eq) and methanol