Palladium(II) catalyzed Suzuki C–C coupling reactions with imino- and amino-phosphine ligands

Article abstract of DOI:10.1016/j.ica.2018.06.013

A new series of bidentate PN type imino- (1–3) and amino-phosphine ligands (4–6) and their palladium(II) complexes [Pd(PN)Cl₂] (1a–6a) have been synthesized and fully characterized using spectroscopic and analytical methods, including ³¹P, ¹H, ¹³C NMR and FTIR spectroscopy and high resolution mass spectroscopy. The catalytic activities of the Pd(II) complexes were investigated for the Suzuki C–C coupling reactions of phenylboronic acid with aryl bromides using a substrate to catalyst ratio of 500/1. The effect of base, temperature and solvent has been investigated, and the highest reaction rates were observed at 80 °C in dimethylformamide (DMF) with K₂CO₃ as the base in 12 h. Under optimized reaction conditions, generally higher coupled product was obtained with substituted aryl bromides, including both electron-withdrawing (-formyl and -aceto) or -donating groups (-methyl and -methoxy) at -ortho or -para positions, except 2-bromoacetophenone which has bulkier -aceto group compared to the other aryl bromides.

Full text of DOI:10.1016/j.ica.2018.06.013

Accepted Manuscript
Research paper
Palladium(II) Catalyzed Suzuki C-C Coupling Reactions with Imino- and Ami-
no-phosphine Ligands
Mustafa Kemal Yılmaz, Simay İnce, Sevilay Yılmaz, Mustafa Keleş
PII:
S0020-1693(18)30620-0
https://doi.org/10.1016/j.ica.2018.06.013
ICA 18305
DOI:
Reference:
Inorganica Chimica Acta
To appear in:
Received Date:
Revised Date:
Accepted Date:
24 April 2018
6 June 2018
7 June 2018
Please cite this article as: M. Kemal Yılmaz, S. İnce, S. Yılmaz, M. Keleş, Palladium(II) Catalyzed Suzuki C-C
Coupling Reactions with Imino- and Amino-phosphine Ligands, Inorganica Chimica Acta (2018), doi: https://
doi.org/10.1016/j.ica.2018.06.013
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Palladium(II) Catalyzed Suzuki C-C Coupling Reactions with Imino- and Amino-
phosphine Ligands
Mustafa Kemal Yılmaza*, Simay İnceb, Sevilay Yılmazc, Mustafa Keleşb
aMersin University, Faculty of Arts and Sciences, Department of Chemistry, 33343 Mersin,
Turkey
bOsmaniye Korkut Ata University, Faculty of Arts and Sciences, Department of Chemistry,
80000 Osmaniye, Turkey
cÇukurova University, Faculty of Arts and Sciences, Department of Chemistry, 01330 Adana,
Turkey
ABSTRACT:
A new series of bidentate PN type imino- (1-3) and amino-phosphine ligands (4-6) and their
palladium(II) complexes [Pd(PN)Cl2] (1a-6a) have been synthesized and fully characterized
using spectroscopic and analytical methods, including 31P, 1H, 13C NMR and FTIR
spectroscopy and high resolution mass spectroscopy. The catalytic activities of the Pd(II)
complexes were investigated for the Suzuki C-C coupling reactions of phenylboronic acid with
aryl bromides using a substrate to catalyst ratio of 500/1. The effect of base, temperature and
solvent has been investigated, and the highest reaction rates were observed at 80°C in
dimethylformamide (DMF) with K2CO3 as the base in 12 h. Under optimized reaction
conditions, generally higher coupled product was obtained with substituted aryl bromides,
*Corresponding author Tel.: +90 324 361 00 01; fax: 90 324 361 00 73
e-mail: mkyilmaz@mersin.edu.tr (MK. Yılmaz)
1

including both electron-withdrawing (-formyl and -aceto) or -donating groups (-methyl and -
methoxy) at -ortho or -para positions, except 2-bromoacetophenone which has bulkier -aceto
group compared to the other aryl bromides.
Keywords: Iminophosphine, aminophosphine, palladium, Suzuki coupling
1. Introduction
The palladium catalyzed Suzuki C-C coupling reaction of organoboron compounds with aryl
halides is one of the most important reaction for the preparation of new C-C bonds in organic
synthesis which has been applied to many areas, such as pharmacological agents, herbicides
and the synthesis of natural products etc. [1-8]. Therefore, researchers have improved and
designed new ligands and catalyst systems to apply this type of reaction. Phosphines and their
palladium complexes play an important role as catalysts for the Suzuki C-C coupling reactions
[9,10]. Sterically hindered and electron rich phosphines, such as trialkylphosphines,
ferrocenyldialkylphosphines and dialkylarylphosphines have been successfully applied in the
Suzuki C-C coupling reactions for a variety of substrates [11,12]. However, in order to obtain
more selective and active catalysts, hemilabile ligands are designed and applied in the Suzuki
C-C coupling reactions. Combining soft and hard donor groups, phosphorus-nitrogen based
(such as pyridine, quinazoline, pyrazole, imidazoline, oxazoline, thiazoline, oxazine based
cyclic ligands or acyclic imine-N-donor ligands) have been applied in C-C coupling reactions
to facilitate substrate interaction with the palladium center and stabilize the intermediates
during the catalytic cycles. In addition, the presence of sp3 (R-NH) or sp2 (=N-R) hybridized
nitrogen donor in the ligand system significantly affects the catalytic performance [13-17].
Herein, we report Suzuki C-C coupling reactions catalyzed by Pd(II) complexes of the imino-
phosphine (1a-3a) and amino-phosphine ligands (4a-6a). A full report on the effect of solvent,
base and temperature for the Suzuki C-C coupling reactions of aryl halides with arylboronic
2

acid was also described. Under the optimized conditions, a variety of electron-donating or
electron-withdrawing groups at ortho position on aryl bromide was well tolerated. The
important advantages associated with our catalyst system are their stability towards air and
moisture.
2. Experimental
2.1. General Comments
All of the reactions were performed under inert atmosphere using conventional Schlenk
glassware. Solvents were dried using established procedures [18] and then immediately
distilled under argon atmosphere prior to being used. FTIR spectra of the ligands and
complexes were recorded with a Perkin Elmer RX1 Spectrophotometer in the range between
4000-650 cm-1. 1H, 31P, and 13C NMR analysis were recorded in CDCl3 at 400.2, 162.0, 100.6
and 376.5 MHz respectively, using Bruker Avance-400 NMR spectrometer at 25°C. The
chemical shifts were given in ppm as δ downfield from SiMe4 as an internal standard. Spin
multiplicities were reported as singlet (s), doublet (d), triplet (t), quartet (q), doublet of doublet
(dd), triplet of doublet (td) with coupling constant (J) given in Hertz (Hz) or multiplet (m).
Melting points were determined on a Mettler Toledo MP90 system and are uncorrected. Gas
chromatography (GC-FID) analyses were performed on a Perkin Elmer Clarus 500 series gas
chromatograph equipped with and a 30 m x 0.25 mm x 0.25 μm film thickness Rxi-5ms
capillary column. HRMS measurements were performed with a Waters series SYNAPT G1
MS model high resolution mass spectrometer. Thin layer chromatography (TLC) was
monitored on a silica gel plates (Merck Kieselgel 60 F254).
2.2. Preparation of ligands and complexes
3

Scheme 1. Synthesis of imino- and amino-phosphine ligands and palladium(II) complexes
2.2.1. 1-(2-(bis(3,5-dimethylphenyl)phosphinyl)phenyl)-N-methylmethanimine (1)
A 20 mL CH2Cl2/CH3OH (1:3) solution of 2-(bis(3,5-
dimethylphenyl)phosphino)benzaldehyde (0.39 g, 1.15 mmol), and ethanol solution (ca. 5 mL)
of methylamine was conducted in Schlenk tube and stirred at room temperature. After 2 hours,
the volatiles were removed under high vacuum. The yellow oily residue was recrystallized in
methanol at -20°C overnight to give the pure imino-phosphine 1 as a white solid. 97% yield
(0.40 g). Melting point: 95.2°C. 1H NMR (400.2 MHz, CDCl3): δ (ppm) 8.99 (d, JPH= 3.8
Hz, CH=N, 1H), 8.01 (dd, J= 3.8, 7.5 Hz, ArH, 1H), 7.37 (t, J= 7.4 Hz, ArH, 1H), 7.29 (t, J=
7.4 Hz, ArH, 1H), 6.97 (s, ArH, 2H), 6.92 (dd, J= 5.3, 7.1 Hz, ArH, 1H), 6.88 (d, J= 8.2 Hz,
ArH, 4H), 3.40 (d, J= 1.3 Hz, NCH3, 3H), 2.25 (s, ArCH3, 12H). 13C NMR (100.6 MHz,
4

CDCl3): δ (ppm) 161.3 (d, JPC= 24.8 Hz), 139.7 (d, JPC= 11.1 Hz), 137.9 (d, JPC= 7.4 Hz),
137.6 (d, JPC= 19.0 Hz), 136.1 (d, JPC= 9.0 Hz), 133.6 (s), 131.6 (d, JPC= 20.0 Hz), 130.6 (s),
130.2 (s), 128.8 (s), 126.7 (d, JPC= 4.4 Hz), 48.1 (s), 21.31 (s). 31P NMR (162.0 MHz,
CDCl3): δ (ppm) -15.46. FT-IR (KBr, cm−1): 1643 (νC=N). HRMS (ESI): calc. [M+H]+ for
C24H26NP 360.1881; found [M+H]+ 360.1896.
2.2.2. 1-(2-(bis(3,5-dimethylphenyl)phosphinyl)phenyl)-N-(tert-butyl)methanimine (2)
2-(bis(3,5-dimethylphenyl)phosphino)benzaldehyde (0.52 g, 1.51 mmol) and 25 mL tert-butyl
amine was conducted in young’s tube and stirred at 50°C overnight. After the required time,
tert-butyl amine was removed and the yellow oily product was dried under high vacuum. (0.55
g, 92%). 1H NMR (400.2 MHz, CDCl3): δ (ppm) 8.71 (d, JPH= 5.2 Hz, CH=N, 1H), 7.86 (m,
ArH, 1H), 7.26 (t, J= 7.4 Hz, ArH, 1H), 7.16 (t, J= 7.1 Hz, ArH, 1H), 6.86 (d, J= 3.7 Hz,
ArH, 4H), 6.84 (s, ArH, 2H), 6.78 (m, ArH, 1H), 2.16 (s, ArCH3, 12H), 0.98 (s, C(CH3)3, 9H).
13C NMR (100.6 MHz, CDCl3): δ (ppm) 153.7 (d, JPC= 22.3 Hz), 139.0 (d, JPC= 16.0 Hz),
136.8 (d, JPC= 7.8 Hz), 134.9 (d, JPC= 8.7 Hz), 131.7 (d, JPC= 1.8 Hz), 130.9 (d, JPC= 20.3 Hz),
129.6 (s), 128.6 (s), 127.6 (s), 125.7 (d, JPC= 3.8 Hz), 56.5 (s), 28.4 (s), 20.2 (s). 31P NMR
(162.0 MHz, CDCl3): δ (ppm) -12.48. FT-IR (KBr, cm−1): 1634 (νC=N). HRMS (ESI): calc.
[M+H]+ for C27H32NP 402.2351; found [M+H]+ 402.2362.
2.2.3. 1-(2-(bis(3,5-dimethylphenyl)phosphinyl)phenyl)-N-phenylmethanimine (3)
50 mL young’s tube was charged with 2-(bis(3,5-dimethylphenyl)phosphino)benzaldehyde
(0.52 g, 1.51 mmol) and aniline (0.14 mL, 1.51 mmol) and the mixture was dissolved in
toluene. After the stirring at 120°C for 12 hours, the volatiles were removed and the yellow
oily product was dried under high vacuum (0.58 g, 92%). 1H NMR (400.2 MHz, CDCl3): δ
9.02 (d, JPH= 5.4 Hz, 1H), 8.15 (m, ArH, 1H), 7.35 (t, J = 7.5 Hz, ArH, 1H), 7.25 (td, J= 1.0,
5

7.5 Hz, ArH, 1H), 7.20 (m, 2H), 7.06 (m, ArH, 1H) 6.85 (m, ArH, 9H), 2.18 (s, ArCH3, 12H).
13C NMR (100.6 MHz, CDCl3): δ 159.3 (d, JPC= 23.9 Hz), 152.0 (s), 139.5 (s), 138.1 (d, JPC=
7.8 Hz), 135.9 (d, JPC= 9.0 Hz), 133.5 (s), 131.9 (d, JPC= 20.3 Hz), 130.8 (s), 128.9 (s), 128.81
(s), 127.5 (d, JPC= 3.8 Hz), 125.8 (s), 121.1 (s), 21.3 (s). 31P NMR (162.0 MHz, CDCl3): δ
(ppm) -13.83. FT-IR (KBr, cm−1): 1619 (νC=N). HRMS (ESI): calc. [M+H]+ for C29H28NP
422.2038; found [M+H]+ 422.2050.
2.2.4. 1-(2-(bis(3,5-dimethylphenyl)phosphinyl)phenyl)-N-methylmethanamine (4)
NaBH4 (0.08 g, 2.15 mmol) was added to a solution of imino-phosphine ligand 1 in 15 mL
methanol (0.19 g, 0.54 mmol) and the mixture was stirred for 1 hour at room temperature. The
solvent was removed and the remaining product was dissolved in dichloromethane, and
washed with H2O. The resulting organic phase was dried with Na2SO4, solvent was removed
and the pure amino-phosphine 4 was obtained as a colorless oily product. (0.19 g, 95%) 1H
NMR (400.2 MHz, CDCl3): δ (ppm) 7.65 (dd, J= 7.1, 4.6 Hz, ArH, 1H), 7.30 (td, J= 7.5, 1.1
Hz, ArH, 1H), 7.19-7.13 (m, ArH, 1H), 7.06 (d, J= 12.7 Hz, ArH, 1H), 6.91 (s, ArH, 2H), 6.78
(d, J= 8.4 Hz, ArH, 4H), 4.12 (s, ArCH2, 2H), 2.38 (s, NCH3, 3H), 2.18 (s, ArCH3, 12H). 31P
NMR (162.0 MHz, CDCl3): δ (ppm) -15.69. HRMS (ESI): calc. [M+H]+ for C24H28NP
362.2038; found [M+H]+ 362.2050.
Ligand 5 and 6 were prepared using procedure for 4.
2.2.5. 1-(2-(bis(3,5-dimethylphenyl)phosphinyl)phenyl)-N-(tert-butyl)methanamine (5)
96%, 0.51 g. 1H NMR (400.2 MHz, CDCl3): δ (ppm) 7.43-7.37 (m, ArH, 1H), 7.25-7.21 (m,
ArH, 1H), 7.13 (d, J= 13.5 Hz, ArH, 1H), 7.07 (t, J= 7.0 Hz, ArH, 1H), 6.90 (s, 2H), 6.82 (d,
J= 8.0 Hz, 4H), 3.81 (s, ArCH2, 2H), 2.18 (s, ArCH3, 12H), 0.93 (s, C(CH3)3, 9H). 13C NMR
(100.6 MHz, CDCl3): δ (ppm) 137.9 (d, JPC= 7.4 Hz), 136.6 (d, JPC= 9.7 Hz), 136.2 (d,
6

JPC=13.6 Hz), 133.4 (s), 131.8 (d, JPC= 20.2 Hz), 130.5 (s), 129.9 (d, JPC= 4.9 Hz), 129.5 (d,
JPC= 9.7 Hz), 129.1 (s), 126.99 (s), 50.7 (s), 45.9 (d, JPC= 9.6 Hz, ArCH2), 28.8 (s), 21.3 (s).
31P NMR (162.0 MHz, CDCl3): δ (ppm) -15.45. HRMS (ESI): calc. [M+H]+ for C27H34NP
404.2507; found [M+H]+ 404.2528.
2.2.6. 1-(2-(bis(3,5-dimethylphenyl)phosphinyl)phenyl)-N-phenylmethanamine (6)
96%, 0.33 g. 1H NMR (400.2 MHz, CDCl3): δ 7.36 (m, ArH, 1H), 7.19 (t, J= 7.4 Hz, ArH,
1H), 7.10 (m, ArH, 1H), 6.98 (t, J= 7.8 Hz, ArH, 2H), 6.89 (s, ArH, 2H), 6.85 (m, 1H), 6.81
(d, J= 8.1 Hz, ArH, 4H), 6.55 (t, J= 7.2 Hz, ArH, 1H), 6.28 (d, J= 8.1 Hz, ArH, 2H), 4.38 (s,
ArCH2, 2H), 2.16 (s, ArCH3, 12H). 13C NMR (100.6 MHz, CDCl3): δ 146.8 (s), 142.1 (d,
JPC= 22.8 Hz), 136.9 (d, JPC= 7.4 Hz), 135.2 (d, JPC= 15.3 Hz), 134.9 (d, JPC= 9.0 Hz),
132.54 (s), 130.7 (d, JPC= 20.0 Hz), 129.6 (s), 127.7 (s), 126.9 (d, JPC= 5.1 Hz), 126.2 (s),
116.2 (s), 111.9 (s), 45.9 (d, JPC= 23.1 Hz, ArCH2), 20.3 (s). 31P NMR (162.0 MHz, CDCl3):
δ (ppm) -16.06. HRMS (ESI): calc. [M+H]+ for C29H30NP 424.2194; found [M+H]+
424.2202.
2.3. Preparation of Pd(II) complexes
2.3.1. Dichloro{1-(2-(bis(3,5-dimethylphenyl)phosphinyl)phenyl)-N-methylmethanimine}-
palladium(II) (1a)
A solution of N-methyl-2-(bis(3,5-dimethylphenyl)phosphino)benzylimine (1) (0.32 g, 0.89
mmol) in CH2Cl2(10 mL) was added to a solution of Pd(COD)Cl2 (0.25 g, 0.89 mmol) in
CH2Cl2 (10 mL). The mixture was stirred for 30 minutes at room temperature. After the
completion of the reaction, the volatiles were removed in vacuo and diethyl ether was added to
precipitate the yellow product. The resulting solid was washed with diethylether (4×5 mL) and
dried under vacuum to give complex 1a. Yield 95% (0.45 g). 1H NMR (400.2 MHz, CDCl3):
7

δ (ppm) 8.01 (s, CH=N, 1H), 7.67-7.60 (m, ArH, 2H), 7.50 (t, J= 6.0 Hz, ArH, 1H), 7.10 (s,
ArH, 2H), 7.03 (d, J= 13.4 Hz, ArH, 5H), 3.88 (s, NCH3, 3H), 2.23 (s, ArCH3, 12H). 13C
NMR (100.6 MHz, CDCl3): δ (ppm) 164.4 (d, JPC= 8.9 Hz), 138.6 (d, JPC= 12.7 Hz), 136.8
(d, JPC= 15.1 Hz), 135.1 (d, JPC= 8.6 Hz), 134.3 (d, JPC= 2.9 Hz), 133.5-133.4 (m), 132.4 (d,
JPC= 2.4 Hz), 131.9 (d, JPC= 11.3 Hz), 125.1 (s), 124.5 (s), 123.7 (s), 123.2 (s), 54.3 (s), 21.3
(s). 31P NMR (162.0 MHz, CDCl3): δ (ppm) 32.23 (s). FT-IR (KBr, cm−1): 1642 (νC=N).
HRMS (ESI): calc. [M+Na]+ for C24H26Cl2NPPd 560.0117; found [M+Na]+ 560.0157.
The Pd(II) complexes 2a-6a were prepared using procedure for 1a.
2.3.2. Dichloro{1-(2-(bis(3,5-dimethylphenyl)phosphinyl)phenyl)-N-(tert-
butyl)methanimine}-palladium(II) (2a)
(0.51 g, 97%). 1H NMR (400.2 MHz, CDCl3): δ (ppm) 8.03 (s, CH=N, 1H), 7.73-7.62 (m,
ArH, 3H), 7.46 (m, ArH, 2H), 7.11 (s, ArH, 3H), 6.94 (dd, J= 10.1, 7.8 Hz, ArH, 2H), 2.23 (s,
ArCH3, 12H), 1.40 (s, C(CH3)3, 9H). 13C NMR (100.6 MHz, CDCl3): δ (ppm) 164.8 (d, JPC=
8.2 Hz), 138.9 (d, JPC= 14.9 Hz), 138.5 (d, JPC= 7.1 Hz), 135.1 (d, JPC= 8.7 Hz), 134.2 (d,
JPC= 3.0 Hz), 133.3 (d, JPC= 8.3 Hz), 132.6 (d, JPC= 3.9 Hz), 132.5 (d, JPC= 2.6 Hz), 122.9
(s), 122.4 (s), 64.5 (s), 31.79 (s), 21.3 (s). 31P NMR (162.0 MHz, CDCl3): δ (ppm) 32.65 (s).
FT-IR (KBr, cm−1): 1619 (νC=N). HRMS (ESI): calc. [M+Na]+ for C27H32Cl2NPPd 602.0586;
found [M+Na]+ 602.0677.
2.3.3. Dichloro{1-(2-(bis(3,5-dimethylphenyl)phosphinyl)phenyl)-N-phenylmethanimine}-
palladium(II) (3a)
(0.53 g, 97%). 1H NMR (400.2 MHz, CDCl3): δ 8.19 (s, CH=N, 1H), 7.84 (m, ArH, 1H), 7.78
(t, J= 7.2 Hz, ArH, 1H), 7.63 (t, J= 7.2 Hz, ArH, 1H), 7.42 (d, J= 7.4 Hz, ArH, 2H), 7.30 (m,
8

ArH, 3H), 7.19 (d, J= 13.1 Hz, ArH, 6H), 7.12 (m, ArH, 1H), 2.34 (s, ArCH3, 12H). 13C NMR
(100.6 MHz, CDCl3): δ 164.9 (d, JPC= 8.5 Hz), 151.8 (s), 138.8 (d, JPC= 12.7 Hz), 136.9 (d,
JPC= 14.5 Hz), 136.3 (d, JPC= 8.3 Hz), 134.3 (d, JPC= 2.9 Hz), 133.9 (d, JPC= 7.8 Hz), 133.8 (d,
JPC= 3.0 Hz), 132.7 (d, JPC= 2.3 Hz), 131.9 (d, JPC= 11.3 Hz), 128.6 (s), 128.1 (s), 125.2 (s),
124.6 (s), 123.4 (s), 21.3 (s). 31P NMR (162.0 MHz, CDCl3): δ (ppm) 31.23 (s). FT-IR
(KBr, cm−1): 1584 (νC=N). HRMS (ESI): calc. [M+Na]+ for C29H28Cl2NPPd 622.0273; found
[M+Na]+ 622.0345.
2.3.4. Dichloro{1-(2-(bis(3,5-dimethylphenyl)phosphinyl)phenyl)-N-methylmethanamine}-
palladium(II) (4a)
(0.49 g, 98%). 1H NMR (400.2 MHz, CDCl3): δ (ppm) 7.48 (t, J= 6.8 Hz, ArH, 1H), 7.36-
7.28 (m, ArH, 3H), 7.26 (s, ArH, 1H), 7.05 (t, J= 14.4 Hz, ArH, 4H), 6.84-6.80 (m, ArH, 1H),
5.65 (s, NH, 1H), 3.90 (d, JPH= 13.0 Hz, ArCH2, 1H), 3.74 (m, ArCH2, 1H), 2.50 (s, NCH3,
3H), 2.22 (s, 12H). 13C NMR (100.6 MHz, CDCl3): δ (ppm) 138.9 (d, JPC= 4.0 Hz), 138.7 (d,
JPC= 5.6 Hz), 138.1 (d, JPC= 13.0 Hz), 134.2-133.9 (m), 133.6 (d, JPC= 3.0 Hz), 132.6 (d, JPC=
8.4 Hz), 132.2 (d, JPC= 11.2 Hz), 131.9 (d, JPC= 11.8 Hz), 129.9 (d, JPC= 7.9 Hz), 127.5 (s),
126.9 (s), 125.2 (s), 124.6 (d, JPC= 10.3 Hz), 124.0 (s), 55.8 (d, JPC= 11.0 Hz, ArCH2), 39.3 (s),
21.4 (s). 31P NMR (162.0 MHz, CDCl3): δ (ppm) 20.71 (s). HRMS (ESI): calc. [M+Na]+ for
C24H28Cl2NPPd 562.0273; found [M+Na]+ 562.0707.
2.3.5. Dichloro{1-(2-(bis(3,5-dimethylphenyl)phosphinyl)phenyl)-N-(tert-
butyl)methanamine}-palladium(II) (5a)
(0.51 g, 98%). 1H NMR (400.2 MHz, CDCl3): δ (ppm) 7.46 (t, J= 7.5 Hz, ArH, 1H), 7.35-
7.28 (m, ArH, 4H), 7.16 (d, J= 12.8, ArH, 2H), 7.15-7.08 (m, ArH, 2H), 7.00 (s, ArH, 1H),
5.43 (d, J= 22.4, NH, 1H), 4.44 (dd, JPH= 14.7, 2.8 Hz, ArCH2, 1H), 4.18 (ddd, JPH=14.8, 6.8,
9

2.4 Hz, ArCH2, 1H), 2.27 (s, ArCH3, 6H), 2.17 (s, ArCH3, 6H), 1.19 (s, C(CH3)3, 9H). 13C
NMR (100.6 MHz, CDCl3): δ (ppm) 141.0 (d, JPC= 14.5 Hz), 138.3 (t, JPC= 12.8 Hz), 133.9
(d, JPC= 1.53 Hz), 133.7 (d, JPC= 3.0 Hz), 133.3 (d, JPC= 2.9 Hz), 132.2 (d, JPC= 11.2 Hz),
131.8 (d, JPC= 3.2 Hz), 129.5 (d, JPC= 7.5 Hz), 129.0 (s), 128.4 (s), 127.2 (s), 126.6 (s), 125.5
(s), 125.1 (s), 60.5 (s), 52.5 (d, JPC= 9.5 Hz, ArCH2), 30.8 (s), 21.4 (d, JPC= 6.6 Hz). 31P NMR
(162.0 MHz, CDCl3): δ (ppm) 17.57 (s). HRMS (ESI): calc. [M+Na]+ for C27H34Cl2NPPd
604.0743; found [M+Na]+ 604.0748.
2.3.6. Dichloro{1-(2-(bis(3,5-dimethylphenyl)phosphinyl)phenyl)-N-phenylmethanamine}-
palladium(II) (6a)
(0.53 g, 97%). 1H NMR (400.2 MHz, CDCl3): δ 7.85 (s, ArH, 1H), 7.49-7.45 (m, ArH, 3H),
7.42 (s, ArH, 1H), 7.34 (dd, J= 4.5, 2.9 Hz, ArH, 2H), 7.24 (d, J= 13.7 Hz, ArH, 2H), 7.19 (s,
ArH, 2H), 7.13 (m, ArH, 2H), 6.95 (m, ArH, 1H), 6.86 (dd, J= 8.4, 4.4 Hz, ArH, 1H), 6.33 (s,
NH, 1H), 4.33 (d, JPH= 13.1 Hz, ArCH2, 1H), 4.13 (dd, JPH= 10.6, 8.2 Hz, ArCH2, 1H), 2.37
(s, ArCH3, 6H), 2.29 (s, ArCH3, 6H). 13C NMR (100.6 MHz, CDCl3): δ 143.8 (s), 139.2 (d,
JPC= 14.0 Hz), 138.8 (d, JPC= 12.2 Hz), 138.2 (d, JPC= 12.9 Hz), 134.1 (d, JPC= 2.8 Hz), 133.6
(d, JPC= 2.8 Hz), 133.5 (d, JPC= 3.1 Hz), 132.8 (d, JPC= 8.5 Hz), 132.3 (d, JPC= 11.2 Hz), 131.9
(d, JPC= 11.2 Hz), 131.8 (d, JPC= 2.1 Hz), 129.6 (d, JPC= 8.0 Hz), 128.8 (s), 127.4 (s), 127.1
(s), 126.7 (s), 126.0 (s), 125.8 (s), 58.2 (d, JPC= 11.5 Hz, ArCH2), 21.4 (d, JPC= 7.2 Hz). 31P
NMR (162.0 MHz, CDCl3): δ (ppm) 21.11 (s). HRMS (ESI): calc. [M+Na]+ for
C29H30Cl2NPPd 624.0430; found [M+Na]+ 624.0494.
2.4. General procedure for Suzuki C-C coupling reactions
In a typical experiment, a sealed tube was charged with aryl bromide (0.10 mmol),
phenylboronic acid (0.12 mmol), base (0.12 mmol), organic solvent-H2O (3:3 mL) and
10

palladium catalyst (0.2 mol%), and the mixture was stirred at appropriate temperature. After
the required reaction time, the mixture was cooled and poured out in CHCl3 (20 mL) and
washed with saturated ammonium chloride and brine solution. Then, the organic phase was
dried over anhydrous sodium sulfate, and the solvent was evaporated. The crude product was
chromatographed on silica gel and the isolated biphenyl product was characterized by 1H, 13C
NMR, and GC.
3. Results and Discussion
3.1. Synthesis
The synthetic routes of the imino- and amino-phosphine ligands and their palladium(II)
complexes were outlined in Scheme 1. 2-bis-(3,5-dimethylphenylphosphino)benzaldehyde
[19,20] was firstly reacted with methylamine, tert-butylamine and aniline to afford 1-(2-
(bis(3,5-dimethylphenyl)phosphino)phenyl)-N-methylmethanimine (1), 1-(2-(bis(3,5-dimethyl
phenyl)phosphino)phenyl)-N-(tert-butyl)methanimine (2) and 1-(2-(bis(3,5-dimethylphenyl)
phosphino)phenyl)-N-phenylmethanimine (3) as a white solid or colorless oily products,
respectively [15,20,21]. The classical reduction of imine groups with NaBH4 in methanol,
followed by extraction with dichloromethane and water and dried over Na2SO4, afforded
amino-phosphine compounds 1-(2-(bis(3,5-dimethylphenyl)phosphino)phenyl)-N-
methylmethanamine (4), 1-(2-(bis(3,5-dimethylphenyl)phosphino)phenyl)-N-(tert-
butyl)methanamine (5) and 1-(2-(bis(3,5-dimethylphenyl)phosphino)phenyl)-N-
phenylmethanamine (6) as a colorless oily products [22-24].
The reaction of corresponding PN type ligands (1-6) with dichloro(1,5-cyclooctadiene)
palladium(II) [25] in CH2Cl2 gave palladium(II) complexes (1a-6a) as yellow solids by the
following general procedures. All the palladium(II) complexes have been found to be
11

completely air and moisture stable and can be handled in the air for weeks. They are readily
soluble in methanol, dichloromethane, chloroform, dimethylformamide and acetonitrile, but
poorly soluble in other commonly used organic solvents such as toluene, THF or 1,4-dioxane.
3.2. Characterization
All of the ligands and Pd(II) complexes have been fully characterized using FT-IR, 1H, 31P and
13C NMR spectroscopy and they were further characterized by HRMS analysis. The 1H NMR
spectra of compound 1, 2 and 3 showed a characteristic doublet for the imine proton which
related to the coupling of the phosphorus with the imine hydrogen at 8.99 ppm (JPH= 3.8 Hz),
8.71 ppm (JPH= 5.2 Hz) and 9.02 (JPH= 5.4 Hz), respectively. Also, the 13C NMR spectra
exhibited characteristic doublet signals of the imine carbons resonated at 161.3 (JPC= 24.8 Hz)
(1), 153.7 (JPC= 22.3 Hz) (2) and 159.3 (JPC= 23.9 Hz) ppm (3), respectively. The 1H NMR
spectra of Pd(II) complexes displayed singlet peaks at 8.01 (1a) 8.03 (2a) and 8.19 (3a) ppm,
showing that the phosphine coordinated palladium considerably de-shielded compared to the
free ligands. Meanwhile, based on 13C NMR analysis, the signal of imine carbons of metal
complexes de-shielded and were found to occur in the range 164.4-164.9 ppm (with 8.2-8.9
Hz), as compared to its PN ligands after complexations to the metal ion through imine nitrogen
of the ligands. Besides that, all of the 1H NMR peaks observed between 8.15-6.78 ppm,
assigned to aromatic CH protons of ligands (1-3) and complexes (1a-3a). In addition, the
methyl protons attached to the phenyl rings gave singlet peaks at 2.25, 2.16 and 2.17 ppm for
compound 1, 2 and 3, and the NCH3 and C(CH3)3 resonances were observed at 3.40 (d,
JPH=1.3 Hz, probably due to phosphorus coupling) and 0.98 ppm (s) for compound 1 and 2, as
expected [15,17,26]. Reduction of the compounds 1-3 was performed in methanol with 4 mole
equivalents NaBH4 to give amino-phosphine ligands (4-6). The 1H NMR spectra of ligand 4-6
showed singlet resonance at 4.12 (4), 3.81 (5) and 4.38 (6) ppm which are assigned to Ar-CH2
12

protons together with disappearance of imine doublet at 8.99, 8.71 and 9.02 ppm indicating the
reduction of imine groups to amino- groups [15,17,22,24,27,28]. In 1H NMR of palladium
complexes, two sets of signals (3.90 (d) and 3.74 (m) for 4a; 4.44 (dd) and 4.18 (ddd) for 5a;
4.33 (d) and 4.13 (dd) for 6a) were recorded for each proton of methylene group probably due
to the rotation of -CH2- hydrogens and coupling of phosphorus with the methylene hydrogen
similar to that of phosphorus with corresponding imine hydrogen. The formation of
palladium(II) complexes were also confirmed by 13C NMR analysis. This is a downfield shift
from 45.9-54.3 to 52.5-58.2 ppm observed for methylene carbons of the amino-phosphine
ligands, further confirming the coordination of the nitrogen donor to the palladium center
[20,21,29,30]. The 31P NMR spectrum showed singlet resonances at -15.46, -12.48 and 13.83
ppm assigned to ligand 1-3 and after the reduction of imine group with excess NaBH4, the
signals were shifted to -15.69, -15.45 and -16.06 ppm for ligand 4-6, respectively [17,29].
These signals have totally disappeared and low field singlet has newly formed (32.23 (1a),
32.65 (2a), 31.23 (3a), 20.71 (4a), 17.57 (5a) and 21.11 (6a) ppm) in the 31P NMR spectra of
the Pd(II) complexes which further support the coordination of the phosphorus atom to the
palladium center [31,32]. Thus, as expected, the spectroscopic results and high resolution mass
data together support the purposed structures (see the supporting information).
3.3. Suzuki coupling reactions
The nature of the base, solvent, temperature and catalyst amount is more important for the
Suzuki C-C coupling reactions. So, we first chose bromobenzene and phenylboronic acid as
the model substrates to optimize the catalytic conditions, including optimization of the bases,
solvents and temperatures. For this purpose, we have tested common inorganic and organic
bases such as KOH, K2CO3, Na2CO3, K3PO4, NaOAc, Et3N, ButOK, NaOH and DIPEA at
80°C as shown in Table 1 and in all cases the reactions were performed with 0.2 mol% of
13

catalyst. While the reaction proceeds with various bases and solvents, the best result was
obtained with K2CO3 as the base and DMF was found to be the best solvent at 80°C (entries 2
and 12). Thereafter, coupling of phenylboronic acid was carried out in toluene as solvent and
no coupling product was obtained (entry 20). It is well-known that generally non-polar
solvents like toluene are not preferred for the Suzuki C-C coupling reactions as they allow for
the lower solubility of both the substrates and catalysts used [20,21,33,34]. In addition, no
coupling product was also observed in the absence of base (entry 10), which is essential to
generate the catalytically active species and facilitate the transmetalation step. In Suzuki
coupling reactions, the use of weak bases remains unable to activate phenylboronic acid,
whereas strong bases limit the functional group tolerance [35]. The use of commonly inorganic
bases such as KOH, Na2CO3, K3PO4, NaOH, and organic bases like Et3N, NaOAc, ButOK or
DIPEA, lead to the formation of coupling products in moderate yields (entries, 1, 3-9, 11, and
13-19).
On the other hand, the reaction temperature has a great effect on the yield of coupling product.
In high temperature Suzuki C-C coupling reactions, the effect of temperature results in
palladium black formation whereas lower temperature does not accelerate the oxidative
addition of aryl bromides which is rate determining step of a Suzuki C-C coupling reaction
[13,36]. In order to study the effect of temperature on coupling of phenylboronic acid with
bromobenzene, the reaction temperature was decreased to 50°C which decreased the yield of
cross coupling product to 55% (entry 2). Thus, the best reaction temperature was found to be
80°C, which is adequately suitable for the activation of bromobenzene without palladium
black formation.
Table 1. The effect of base, solvent and temperature on the Pd(II) catalyzed
Suzuki C-C coupling reaction between bromobenzene and phenylboronic
acid with catalyst 2aa
14

Yield (80°C)b
Entry
Solvent
Base
DMF
DMF
KOH
60
89 (55)c
60
61
69
40
64
29
67
-
1
2
K2CO3
Na2CO3
NaOAc
Et3N
ButOK
K3PO4
NaOH
DIPEA
-
DMF
DMF
3
4
DMF
DMF
5
6
DMF
DMF
7
8
DMF
DMF
9
10
11
12
13
14
15
16
17
18
19
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
KOH
70
78
65
34
73
67
65
62
55
K2CO3
Na2CO3
NaOAc
Et3N
ButOK
K3PO4
NaOH
DIPEA
toluene
K2CO3
-
20
aReaction conditions: bromobenzene (0.1 mmol), phenylboronic acid (0.12 mmol), catalyst
2a (0.2 mol%), base (0.12 mmol), solvent (2.0 mL), H2O (2.0 mL), 12 h.
bBıphenyl product was isolated from the reaction mixture and was characterized by 1H, 13
C
NMR, and GC
c50 °C.
Next, the performance of Pd(II) catalysts on Suzuki C-C coupling reactions was further
investigated for different aryl bromides and phenylboronic acid under the optimized
conditions. The results are presented in Table 2. Coupling of phenylboronic acid with para-
substituted aryl bromides gave desired coupled product with a good to excellent isolated yields
by all catalysts in 12 hours (up to 99% yield, Table 2, entries 1, 4, 5, and 7). Generally, for the
Suzuki C-C coupling reactions, the use of deactivated aryl bromides, substituted with electron
donating groups such as -methyl or -methoxy, slows down the rate of the reaction [13,20,21].
15

However, both electron-withdrawing and -donating groups on the phenyl ring at para position
of aryl bromides did not seem to have a great effect on the product yields apparently.
Comparing the efficiency of the catalysts, the poorest results (78%) are obtained with
deactivated substrate 4-bromotoluene when 2a and 4a are used as catalysts (entry 1) while the
coupling of another deactivated 4-bromoanisole with phenylboronic acid goes to almost
completion (>99) in 12 h with all catalysts (entry 4). The catalytic system is also efficient for
the coupling of 3-bromobenzophenone with phenylboronic acid and thus 3-
phenylbenzophenone was obtained in high yields (86-97%, entry 10). On the other hand, the
presence of electron-withdrawing or -donating groups in the ortho position on the aryl
bromides, significantly influences the catalyst performance leading to reduced reaction rates
[13,37]. This effect suggests that, with sterically hindered aryl bromides, the oxidative addition
of the substrate to the palladium center is the rate determining step in the Suzuki C-C coupling
reaction and ultimately decreasing the rate of reaction. Importantly, the coupling of ortho
substituted substrates such as 2-bromotoluene, 2-bromoanisole and 2-bromobenzaldehyde with
phenylboronic acid generally gave coupled products in moderate to good yields (from 43-89%)
and steric effects of these groups were well tolerated (entries, 2, 3 and 6). But, in the case of 2-
bromoacetophenone, only 10% and 12% desired product was obtained with catalyst 5a and 6a,
respectively and no significant product was observed with catalyst 1a-4a. These results clearly
indicate that, the strong steric effect of the bulkier -aceto group in the 2-bromoacetophenone
has a great influence on the catalytic activity of the complexes when comparing to the other
sterically hindered substrates containing relatively less bulky substituents such as -methyl, -
methoxy and -formyl groups (entries 2, 3, 6, and 8). Besides, the catalytic efficiency of our
catalyst system is highly slowed down (<5 to 12%) for the heterocoupled product when 2-
bromopyridine was used as a substrate (entry 9). The catalytic activities of palladium catalysts
1a-6a were also tested in the Suzuki coupling of industrially important substrate 3-
16

bromobenzophenone with phenylboronic acid and good to excellent coupled product was
isolated (86-97%, entry 10).
Normally, the presence of “imino group” rather than “amino group” in the ligand
system will increase the -donor ability of the nitrogen donor and so the palladium center will
be more susceptible to oxidative addition reactions, but surprisingly, comparing the results
obtained for 1a-3a and 4a-6a catalysts, no significant difference was found in catalytic activity
of the complexes. On the other hand, Mahamo and coworkers reported the use of well-defined
methyl chloride and dichloride iminophosphine Pd(II) complexes as pre-catalysts in Suzuki C-
C coupling reactions which have benzyl, furfuryl and thiophenyl groups on the imine nitrogen
of the ligands. They observed that for this catalyst system, the presence of methylene group
which bonded to nitrogen donor, reduced the steric crowding and improves conversions and
activities [13]. However, comparing the results obtained from our catalyst system, sterically
hindered substrates of both electron-withdrawing and electron-donating groups on the aryl
bromide were well tolerated and the reactions were carried out under relatively mild
temperature.
Table.2. The effect of the catalysts on the Suzuki C-C coupling reactions of
between substituted aryl bromides and phenylboronic acida
Yield (%)b
Entry ArBr
1
Product
5a 6a
1a
2a 3a 4a
86
78 93 78
86 95
59
53
70 87 65
86 53
44 89
2
3
68 49 43
17

94
95 98 >99 94 97
4
5
>99 95 94 96
97 98
56 48
60
88
85 89 58
6
7
93 99 96
90 96
<5
<5 <5 <5
12 10
8
<5
95
25 20 <5
97 97 86
16
8
9
94 88
10
aReaction conditions.: aryl bromide (0.1 mmol), phenylboronic acid (0.12 mmol), catalyst (0.2
mol%), K2CO3 (0.12 mmol), DMF (2.0 mL), H2O (2.0 mL), T: 80°C, 12 h.
bBiaryl products were isolated from the reaction mixture and were characterized by 1H, 13C NMR,
and GC.
4. Conclusion
Several new imino- and amino-phosphine ligands and their palladium(II) complexes have been
synthesized and characterized by spectrocopic and analytical methods. Based on the NMR,
FTIR and HRMS analyses, the imino- and amino-phosphine ligands acted as PN bidentate
ligand and have bonded to the palladium center via nitrogen and phosphorus donors. These
palladium(II) complexes were used as catalyst precursors for the Suzuki C-C coupling of
substituted aryl bromides bearing activated or deactivated group at -ortho or -para positions.
18

The results show that, good to excellent coupling products were obtained for these imino- and
amino-phosphine palladium catalysts and sterically hindered substrates were well tolerated.
Acknowledgements
This work was supported by the Osmaniye Korkut Ata University (Project Number:
OKUBAP-2017-PT2-003).
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20

Graphical abstract
21

Research Highlights



PN type imino- and amino phosphine ligands and their Pd(II) complexes have been
synthesized.
These Pd(II) complexes [Pd(PN)Cl2] have been applied for the Suzuki C-C coupling
reactions.
Good to excellent coupling products were obtained and sterically hindered substrates
were well tolerated.
22