Single monodentate N-donor ligands versus multi-ligand analogues in Pd(II)-catalysed C–C coupling at reduced temperatures

Article abstract of DOI:10.1016/j.poly.2020.114507

Deployment of reduced operational temperatures is industrially beneficial and use of the highly efficient, phosphine-based precatalysts is limited by their high costs and inaccessible preparation procedures. In order to study of the influence of coordination environments on catalyst reactivities at reduced temperatures, design of palladium(II) complexes bearing single monodentate N-donor ligands was considered necessary. Consequently, dichloridopalladium(II) complexes of 2-(thiophen-2-yl)-1H-imidazole ligands (1–8), 2,4,5-triphenyloxazole (9) and 2-(1H-imidazol-2-yl)pyridine (10) have been prepared, structurally characterized and studied as N-stabilized precatalysts. Ligand donor strengths were spectroscopically estimated by protonation-deprotonation equilibria. The palladium(II) complexes were obtained in three coordination environments; (i) the mono-ligand complexes bearing trans-solvent co-ligands (PdL.acn and PdL.dmf), (ii) the chlorido-bridged dimers μ-(PdL)₂ and (iii) the trans-bis-ligand PdL₂ complexes. Considering ambient temperature operations, the catalysis outcomes obtained for the monodentate mono-ligand coordination designs represent an improvement in terms of temperature and reaction time relative to previously reported N-stabilized palladium precatalysts. The mono-ligand pre-catalysts efficiently generate living active palladium species from 40 °C while a trans-bis-ligand phosphine-based pre-catalyst analogue PdI₂(PPh₃)₂ displayed no yield under the same temperature conditions. Trans-bis-ligand coordination is observed to utterly hinders catalyst efficiencies at the studied temperatures and preformed mono-ligand complexes of mono-dentate N-donors provided positive ligand effects while in situ catalyst generation failed. Therefore, the use of multiple ligand equivalents should be discouraged.

Full text of DOI:10.1016/j.poly.2020.114507

Journal Pre-proofs
Single monodentate N-donor ligands versus multi-ligand analogues in Pd(II)-
catalysed C-C coupling at reduced temperatures
Abiodun Omokehinde Eseola, Helmar Görls, Joseph Anthony Orighomisan
Woods, Winfried Plass
PII:
S0277-5387(20)30164-9
DOI:
Reference:
https://doi.org/10.1016/j.poly.2020.114507
POLY 114507
To appear in:
Polyhedron
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Revised Date:
Accepted Date:
6 January 2020
4 February 2020
9 March 2020
Please cite this article as: A.O. Eseola, H. Görls, J.A. Orighomisan Woods, W. Plass, Single monodentate N-
donor ligands versus multi-ligand analogues in Pd(II)-catalysed C-C coupling at reduced temperatures,
Polyhedron (2020), doi: https://doi.org/10.1016/j.poly.2020.114507
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Single monodentate N-donor ligands versus multi-ligand analogues in
Pd(II)-catalysed C-C coupling at reduced temperatures
Abiodun Omokehinde Eseola,1,2, Helmar Görls, Joseph Anthony Orighomisan Woods,
1
3
1
,
Winfried Plass
1Institut für Anorganische und Analytische Chemie, Friedrich-Schiller-Universität Jena,
Humboldtstr. 8, D-07743 Jena, Germany.
2
Materials Chemistry group, Department of Chemical Sciences, Redeemer’s University Ede,
Osun State, Nigeria.
3
Inorganic Chemistry Unit, Department of Chemistry, University of Ibadan, Ibadan, Nigeria.
Abstract
Deployment of reduced operational temperatures is industrially beneficial and use of
the highly efficient, phosphine-based precatalysts is limited by their high costs and inaccessible
preparation procedures. In order to study of the influence of coordination environments on
catalyst reactivities at reduced temperatures, design of palladium(II) complexes bearing single
monodentate
N-donor
ligands
was
considered
necessary.
Consequently,
dichloridopalladium(II) complexes of 2-(thiophen-2-yl)-1H-imidazole ligands (1 – 8), 2,4,5-
triphenyloxazole (9) and 2-(1H-imidazol-2-yl)pyridine (10) have been prepared, structurally
characterized and studied as N-stabilized precatalysts. Ligand donor strengths were

Corresponding authors: Dr. A. O. Eseola:- (a) Institut für Anorganische und Analytische Chemie, Friedrich-Schiller-
spectroscopically estimated by protonation-deprotonation equilibria. The palladium(II)
Universität Jena, Humboldtstr. 8, D-07743 Jena, Germany (b) Materials Chemistry group, Department of Chemical Sciences,
Redeemer’s University Ede, Osun State, Nigeria; Tel.: +49(0)15218016407, E-mail: biodun.eseola@uni-jena.de;
bioduneseola@hotmail.com
complexes were obtained in three coordination environments; (i) the mono-ligand complexes

Prof. Dr. W. Plass; Address:- Institut für Anorganische und Analytische Chemie, Friedrich-Schiller-Universität Jena,
Humboldtstr. 8, D-07743 Jena, Germany; Tel.: +49(0)3641 948130; Fax: +49(0)3641948132; e-mail: sekr.plass@uni-jena.de
bearing trans-solvent co-ligands (PdL.acn and PdL.dmf), (ii) the chlorido-bridged dimers µ-
(
PdL) and (iii) the trans-bis-ligand PdL complexes. Considering ambient temperature
2
2
1

operations, the catalysis outcomes obtained for the monodentate mono-ligand coordination
designs represent an improvement in terms of temperature and reaction time relative to
previously reported N-stabilized palladium precatalysts. The mono-ligand pre-catalysts
o
efficiently generate living active palladium species from 40 C while a trans-bis-ligand
phosphine-based pre-catalyst analogue PdI (PPh ) displayed no yield under the same
2
3 2
temperature conditions. Trans-bis-ligand coordination is observed to utterly hinders catalyst
efficiencies at the studied temperatures and preformed mono-ligand complexes of mono-
dentate N-donors provided positive ligand effects while in situ catalyst generation failed.
Therefore, the use of multiple ligand equivalents should be discouraged.
Keywords: Catalyst design; Ambient temperatures; N-Donors; Palladium C – C coupling;
Ligand effects
Introduction
Palladium-mediated coupling methods have become vital tools in organic syntheses and
efforts are still being invested on study of precatalysts systems.[1–3] Current areas of
investigation include catalyst development,[4–6] generation of surface-supported catalyst
technologies[7–10] and mechanistic studies.[11,12] Numerous sophisticated, ligand-based
TM
precatalysts such as PEPPSI , AdBrettPhos Pd G3, APhos Pd G2 and XPhos Pd G1 (Scheme
1
(a)), which are products of intensive research investigations, have been trademarked.[13–15]
However, ligand manipulation is central to catalyst development efforts.[16–18]
While in situ approach builds up the catalyst species from ‘ligand + palladium salt’
ingredients, the preformed palladium complexes often require thermal dissociation of some of
the donor arms in order to afford free coordination sites for catalysis (Scheme 1 (b)).[19]
2

Consequently, the energy barrier for decomposition of a precatalyst should depend on donor
strengths, chelating character and the manner in which ligands are assembled around the
palladium metal centre. Thus, careful selection of coordinating species may aid realization of
active precatalyst complexes that do not require high reaction temperatures before freeing up
catalytic coordination sites.
These presently high-performing palladium complexes, which are generally phosphine-
or organometallic-based,[20–22] have been quite successful in the context of substrate scope
and catalytic conversion efficiencies, but the aspect of cost effectiveness could still be
improved upon. Several heating hours are also sometimes even necessary for some of them.[23]
However, a careful examination of their coordination spheres indicates that only one strong
donor function such as phosphine or N-heterocyclic carbene is often bonded on the palladium
centre while the remaining donors are generally weaker (Scheme 1 (a)). Therefore, it could be
imagined that the highly active catalyst forms generated from such precatalyst architectures
would consist of mono-ligand monodentate Pd–ligand species. The aim of this paper is to study
N-donor palladium(II) precatalyst designs that may generate active species according to the
‘one main donor’ rational. Furthermore, the common use of multiple ligand-to-palladium
equivalents could be seen as ignorant formulations, which are probably responsible for
necessity of high temperature for some catalyst systems.[24–26]
The more affordable and stable N-donor ligands have been hitherto less popular as
organic backbones for palladium in coupling catalyses. Based on our previous results for azole
chelates[27–30] and the few available studies involving monodentate N-donors in palladium-
catalysed C-C coupling (Scheme 1 (c)),[31–35] this paper aims to investigate possible
improvement of catalytic efficiencies for N-stabilized palladium species under ambient
temperature regimes.[36–39] Herein, we present results for dichloridopalladium(II) pre-
catalysts bearing structurally varied N-donors and coordinated solvents; i.e. 2-(thiophen-2-yl)-
3

1
H-imidazoles 1–8, 2,4,5-triphenyloxazole (9) and 2-(1H-imidazol-2-yl)pyridine (10)
(
Scheme 2). Comparison with the phosphine complex PdI (PPh ) is also reported.
2
3 2
(a)
i-Pr i-Pr
Cl
H N
i-Pr
2
Cl
NH2
P
N
Pd
N
H N
i-Pr
P
Pd N
Cl
i-Pr
2
Pd
Cl
P
N
i-Pr
O
S
Pd
i-Pr
i-Pr
i-Pr
O
O
Cl
i-Pr
PEPPSITM-IPr
AdBrettPhos Pd G3
APhos Pd G2
XPhos Pd G1
(b)
Dissociations
heat
Pd0
active species
Build up
Pre-catalysts
L
Ligand + Palladium salt
OH Pd(II) Complex
Solvent
O
OH
O
OH
(c)
B
+
Br
N
OH
H
N
n-BuH
H
N
N
N
O
n-Bu
N
Pd
N
N
N
N
Cl
N
O
N
N
n-Bu
Pd
Time = 4 h
Pd
Cl Pd Cl
n-Bu
N
Cl
o
Cl
Cl
Temp. = 100 C
Yield = 86 %
H
N
Time = 60 min
Time = 30 min
N
Time = 15 min
N
o
o
o
Temp. = 100 C
Temp. = 80 C
Temp. = 45 C
NH n-Bu
2
PF6
Yield = 32 %
Yield = 59 %
n-Bu
Yield = 74 %
Scheme 1: (a) Some commercialized palladium complex pre-catalysts, (b) transformations to
active species realization from different catalyst ingredients and (c) Some reported catalysis
results based on N-donor complexes
Experimental
General information
All starting materials for syntheses as well as substrates for catalytic experiments were
obtained commercially as reagent grade and used as supplied. The intermediate pyrene-4,5-
dione used for preparation of ligand 1 was prepared according to reported procedure.[40] The
ligand 2,4,5-triphenyloxazole (9) was obtained as by-product during chromatographic
purification of imidazole condensation reactions between benzil and poorly reactive aldehydes.
4

The complex PdI (PPh ) was obtained during column chromatography purification of the
2
3 2
product of a Sonogashira reaction in which 10 % catalyst components made up of palladium
acetate, CuI and PPh were deployed. In order to exclude impurities in the other synthesized
3
ligands, the organic compounds were routinely purified on silica gel columns. Elemental
1
13
analyses were performed on Leco CHNS-932 or El Vario III elemental analysers. H and C
NMR spectra were recorded on Bruker ARX 400 or 600 MHz instrument using deuterated
solvents as internal standard. IR spectra were recorded on Shimadzu 8740 FT-IR spectrometer
using KBr discs or on Bruker Equinox spectrometer equipped with a diamond ATR unit.
Preparation of the 1H-Imidazolyl ligand analogues
Owing to similarities in the imidazole synthetic procedures, the complete procedure of
compound 5 is presented as a typical reaction procedure while the rest report the basic synthetic
information details.
1
-Phenyl-2-(thiophen-2-yl)-1H-phenanthro[9,10-d]imidazole (5): Thiophene-2-
carbaldehyde, (1.08 g, 9.6 mmol), phenanthrene-9,10-dione (2.00 g, 9.6 mmol), aniline (0.89
g, 9.6 mmol) and ammonium acetate (2.20 g, 28.8 mmol) were refluxed for four hours in glacial
acetic acid (20 mL). The reaction mixture was cooled, diluted with distilled water and
neutralized with aqueous ammonia. The reaction mixture was extracted three times with ethyl
acetate and the combined extract purified on silica gel column using 3:10 ethyl acetate / hexane
o
as eluent to obtain ligand 5 as colourless crystals (3.25 g, 89 %). Mp. 233 C. Selected IR
-1
1
peaks (ATR, cm ): ν 3089m, 3062s, 1610m, 1594s, 1472vs, 1237vs, 697vs, 692vs. H NMR
(
400 MHz d6-dmso); δ 8.92 (d, J = 8.3 Hz, 1H), 8.87 (d, J = 8.3 Hz, 1H), 8.66 (dd, J = 7.9,
, ppm
0
7
.9 Hz, 1H), 7.90 – 7.74 (m, 3H), 7.73 – 7.66 (m, 3H), 7.63 (dd, J = 5.0, 0.9 Hz, 1H), 7.60 –
.51 (m, 2H), 7.34 (t, J = 7.6 Hz, 1H), 7.08 (d, J = 8.1 Hz, 1H), 7.00 (dd, J = 5.0, 3.8 Hz, 1H),
5

1
3
6
1
1
.71 (dd, J = 3.7, 0.9 Hz, 1H). C NMR (101 MHz, d6-dmso) δ
145.95, 138.25, 136.97,
ppm
33.11, 131.47, 131.34, 129.62, 129.05, 128.94, 128.23, 128.21, 128.17, 127.97, 127.27,
27.20, 126.83, 126.33, 125.77, 124.99, 124.16, 122.72, 122.51, 120.45. EI MS: m/z 376 [M]+
(base peak, calc. 376.10).
1
0-(5-Bromothiophen-2-yl)-9-phenyl-9H-pyreno[4,5-d]imidazole
(1):
5-
Bromothiophene-2-carbaldehyde (0.82 g, 4.3 mmol), pyrene-4,5-dione (1.00 g, 4.3 mmol),
aniline (0.40 g, 4.3 mmol) and ammonium acetate (1.00 g, 12.9 mmol) yielded compound 1.
o
-1
(
1.75 g, 85 %). Mp. 207 C. Selected IR peaks (ATR, cm ): ν 3093m, 3048s, 2956s, 2922vs,
1
1
8
1
596vs, 1497vs, 697s. H NMR (400 MHz, CDCl ): δ
9.09 (s, 1H), 8.21 – 8.17 (m, 1H),
ppm
3
.12 (t, J = 7.6 Hz, 1H), 8.09 (d, J = 8.9 Hz, 1H), 8.02 (t, J = 7.7 Hz, 2H), 7.83 (t, J = 7.3 Hz,
H), 7.76 (t, J = 7.4 Hz, 2H), 7.69 (d, J = 7.2 Hz, 2H), 7.62 (t, J = 7.8 Hz, 1H), 7.30 (d, J = 7.7
1
3
Hz, 1H), 6.89 (d, J = 3.9 Hz, 1H), 6.80 (s, br, 1H). C NMR (101 MHz，CDCl ): δ 132.17,
3
1
1
31.62, 131.00, 130.80, 130.41, 129.25, 127.98, 127.50, 126.44, 125.40, 124.88, 124.56,
+
23.52, 122.90, 120.13, 117.66. EI MS: m/z 479 [M] (base peak, calc. 478.01).
2
-(5-Bromothiophen-2-yl)-1-phenyl-1H-phenanthro[9,10-d]imidazole (2): 5-
Bromothiophene-2-carbaldehyde (0.97 g, 4.4 mmol), phenanthrene-9,10-dione (1.00 g, 4.4
mmol), aniline (0.45 g, 4.3 mmol) and ammonium acetate (1.11 g, 14.4 mmol) gave ligand 2
o
-1
(
1.03 g, 51 %). Mp. 179 C. Selected IR peaks (ATR, cm ): ν 3046s, 1612m, 1594s, 1475vs,
1
1
8
454vs, 752vs, 721vs. H NMR (400 MHz, CDCl ); δ 8.89 (d, J = 6.5 Hz, 1H), 8.77 (d, J =
3
ppm
.4 Hz, 1H), 8.70 (d, J = 8.3 Hz, 1H), 7.83 – 7.72 (m, 3H), 7.68 (t, J = 7.7 Hz, 3H), 7.63 (d, J
7.9 Hz, 1H), 7.53 (dd, J = 8.2, 7.2 Hz, 1H), 7.27 (dd, J = 9.2, 4.8 Hz, 2H), 7.12 (d, J = 8.3
=
1
3
Hz, 1H), 6.89 (d, J = 3.8 Hz, 1H). C NMR (101 MHz，CDCl ): δ 131.00, 129.20, 126.65,
3
ppm
+
1
24.22, 123.10, 120.59. EI MS: m/z 454 [M] (base peak, calc. 454.01).
6

2
-(5-Bromothiophen-2-yl)-1-(3,4-dimethoxyphenyl)-1H-phenanthro[9,10-
d]imidazole (3): 5-Bromothiophene-2-carbaldehyde (0.97, 4.4 mmol), phenanthrene-9,10-
dione (1.00 g, 4.4 mmol), 3,4-dimethoxyaniline (0.80 g, 4.4 mmol) and ammonium acetate
(1.11 g, 14.4 mmol) yielded compound 3 using 3:10 thf / hexane for silica gel chromatography
o
-1
(
1.64 g, 66 %). Mp. 223 C. Selected IR peaks (ATR, cm ): ν 3083m, 3003s, 2944s, 1609m,
1
1
597s, 1511vs, 753vs, 725vs. H NMR (400 MHz, CDCl ); δ 8.84 (s, 1H), 8.73 (d, J = 8.3
3
ppm
Hz, 1H), 8.66 (d, J = 8.3 Hz, 1H), 7.72 (t, J = 7.1 Hz, 1H), 7.63 (t, J = 7.6 Hz, 1H), 7.51 (t, J =
7
.6 Hz, 1H), 7.29 (t, J = 7.6 Hz, 1H), 7.25 – 7.10 (m, 4H), 7.02 (d, J = 2.2 Hz, 1H), 6.90 (d, J
1
3
=
3.6 Hz, 1H), 4.08 (s, 3H), 3.86 (s, 3H). C NMR (101 MHz, CDCl ): δ 124.15, 123.07,
3 ppm
+
1
21.52, 120.62, 111.94, 111.56, 56.38, 56.26. EI MS: m/z 514 [M] (base peak, calc. 514.04).
1
-(3,4-Dimethoxyphenyl)-2-(thiophen-2-yl)-1H-phenanthro[9,10-d]imidazole (4):
Thiophene-2-carbaldehyde (1.08 g, 9.6 mmol), phenanthrene-9,10-dione (2.00 g, 9.6 mmol),
,4-dimethoxyaniline (1.47 g, 9.6 mmol) and ammonium acetate (2.20 g, 28.8 mmol) produced
3
o
-1
ligand 4 (1.89 g, 45 %). Mp. 249 C. Selected IR peaks (ATR, cm ): ν 3114m, 3077m, 2998m,
1
2
837m, 1595s, 1512vs, 1021vs, 722vs. H NMR (400 MHz, d6-dmso); δ 8.91 (d, J = 8.3
ppm
Hz, 1H), 8.87 (d, J = 8.3 Hz, 1H), 8.68 – 8.63 (m, 1H), 7.77 (t, J = 7.3 Hz, 1H), 7.71 – 7.66 (m,
1
8
H), 7.63 (dd, J = 5.1, 0.9 Hz, 1H), 7.56 (t, J = 7.2 Hz, 1H), 7.44 – 7.38 (m, 2H), 7.24 (d, J =
.0 Hz, 1H), 7.05 (dd, J = 5.0, 3.8 Hz, 1H), 6.90 (dd, J = 3.7, 0.9 Hz, 1H), 3.97 (s, 1H), 3.75
1
3
(
s, 1H). C NMR (101 MHz，d6-dmso): δ 150.79, 150.56, 146.33, 136.78, 133.18, 130.44,
ppm
1
1
28.94, 128.85, 128.33, 128.27, 128.17, 127.89, 127.38, 127.32, 126.88, 126.22, 125.70,
24.87, 124.14, 122.90, 122.48, 121.67, 120.65, 112.90, 112.81, 56.53, 56.26. EI MS: m/z 436
+
[
M] (base peak, calc. 436.12).
7

2
-(5-Methylthiophen-2-yl)-4,5-diphenyl-1H-imidazole (6): Benzil (1.00g, 4.8
mmol), 5-methythiophene-2-carboxaldehyde (0.72g, 5.7mmol) and ammonium acetate (5.50g,
1.6mmol) formed ligand 6 after dichloromethane extraction and column chromatography by
7
o
-1
ethyl acetate / hexane (1:2) (0.88 g, 59 %). Mp. 226 C. Selected IR peaks (ATR, cm ): ν
1
3
–
057s, 1664vs, 1592vs, 1449vs, 765s. H NMR (400 MHz, d6-dmso): δ 12.66 (s, 1H), 7.50
ppm
7.39 (m, 7H), 7.38 – 7.31 (m, 1H), 7.28 (t, J = 7.4 Hz, 2H), 7.20 (t, J = 7.3 Hz, 1H), 6.81 (dd,
1
3
J = 3.5, 1.1 Hz, 1H), 2.46 (s, 3H). C NMR (101 MHz, d6-dmso): δ 141.74, 139.77, 136.66,
ppm
1
1
34.91, 131.56, 130.94, 128.74, 128.50, 128.35, 128.28, 128.24, 127.81, 127.51, 127.09,
+
26.61, 126.25, 124.27, 15.01. EI MS: m/z 316 [M] (base peak, calc. 316.10).
2
-(5-Bromothiophen-2-yl)-4,5-diphenyl-1H-imidazole (7): Benzil (1.00 g, 4.8
mmol), 5-bromo-2-thiophenecarboxaldehyde (0.91 g, 4.8 mmol) and ammonium acetate (7.33
g, 95.1 mmol) in acetic acid (10 mL) afforded ligand 5 after silica gel chromatography by 1:4
o
-1
ethyl acetate / hexane (1.09 g, 60 %). Mp 228 C. Selected IR peaks (ATR, cm ): ν 3049m,
1
2
960s, 2923vs, 2742s, 1653s, 1591s, 1494vs, 696vs. H NMR (400 MHz, d6-dmso): δ 12.88
ppm
(s, 1H), 7.53 – 7.42 (m, 7H), 7.40 (d, J = 6.7 Hz, 1H), 7.30 (dd, J = 15.7, 5.6 Hz, 3H), 7.24 (d,
1
3
J = 7.1 Hz, 1H). C NMR (101 MHz, d6-dmso): δ 140.97, 137.45, 136.18, 135.02, 131.81,
ppm
1
31.13, 129.23, 128.76, 128.72, 128.47, 127.53, 127.21, 125.00, 111.97. EI MS: m/z 380 [M]+
(base peak, calc. 380.00).
4
,5-Bis(4-methoxyphenyl)-2-(thiophen-2-yl)-1H-imidazole
(8):
1,2-bis(4-
methoxyphenyl)ethane-1,2-dione (0.87 g, 3.2 mmol), thiophene-2-carbaldehyde (0.36 g, 3.2
mmol), methyl 4-aminobenzoate (0.37 g, 3.2 mmol) and ammonium acetate (0.74 g, 9.6 mmol)
formed compound 8, but chromatography purification on silica gel was deployed using 1:4 of
o
-1
ethyl acetate / hexane (0.21 g, 18 %). Mp. 177 C. Selected IR peaks (ATR, cm ): ν 2960s,
8

1
2
1
4
835m, 1614s, 1574m, 1501vs, 1246vs, 832vs, 701s. H NMR (400 MHz, d6-dmso); δ
ppm
2.61 (s, 1H), 7.65 (dd, J = 3.6, 0.9 Hz, 1H), 7.53 (dd, J = 5.0, 0.8 Hz, 1H), 7.42 (d, J = 8.4 Hz,
H), 7.14 (dd, J = 5.0, 3.7 Hz, 1H), 6.94 (d, J = 17.8 Hz, 2H), 3.78 (s, 6H). 13C NMR (101
+
MHz, d6-dmso): δ 141.4, 134.7, 128.3, 126.4, 124.3, 114.4, 55.6. EI MS: m/z 362 [M] (base
peak, calc. 362.11).
2
-Bromo-6-(4,5-diphenyl-1H-imidazol-2-yl)pyridine (10): Benzil (1.00 g, 4.8
mmol), 6-bromopicolinaldehyde (0.88 g, 4.8 mmol) and ammonium acetate (7.34 g, 95.2
mmol) gave ligand 10 after dichloromethane extraction and purification by 1:6 ethyl acetate /
o
-1
hexane (0.40 g, 22 %). Mp. 245 C. Selected IR peaks (ATR, cm ): ν 3059m, 1578s, 1554s,
1
1
1
3
1
1
445vs, 765vs, 606vs. H NMR (400 MHz, d6-dmso); δ 13.18 (s, 1H), 8.12 (d, J = 7.7 Hz,
ppm
H), 7.84 (t, J = 7.8 Hz, 1H), 7.61 (d, J = 7.8 Hz, 1H), 7.50 (t, J = 7.3 Hz, 4H), 7.43 – 7.36 (m,
1
3
H), 7.30 (t, J = 7.4 Hz, 2H), 7.23 (t, J = 7.1 Hz, 1H). C NMR (101 MHz, d6-dmso): δ
ppm
49.75, 143.83, 140.95, 140.34, 138.22, 128.91, 128.42, 128.23, 128.02, 127.19, 126.78,
+
19.26. EI MS: m/z 375 [M] (base peak, calc. 375.04).
Synthesis of palladium pre-catalysts
The palladium complexes were obtained either by (i) stirring a mixture of a given ligand
and PdCl (CH CN) at room temperature in ethanol (or 1:1 ethanol/chloroform to aid solubility
2
3
2
of 5 for µ-(Pd5) ) or by (ii) isolation of self-assembled crystals from vials where a given ligand
2
and PdCl (CH CN) were layered with a given solvent. Since similar preparative procedures
2
3
2
were utilized, the procedure for preparation of complex µ-(Pd1) is reported as typical, while
2
the analytical data for each complex species obtained are listed below:
9

µ-(Pd1) : Ligand 1 (76 mg, 0.16 mmol), PdCl (CH CN) (40 mg, 0.16 mmol) were
2
2
3
2
placed into a round bottomed flask. Ethanol (1 mL) was added and the reaction mixture was
stirred for 2 hours at room temperature. The precipitated complex was filtered under suction
and washed with ethanol. The filtered complex was then air dried to obtain µ-(Pd1) (80 mg,
2
o
-1
8
1
0 %). Mp. (with decomposition) 353 C. Selected IR peaks (ATR, cm ): ν 3203s, 1594s,
1
498vs, 970s, 680vs, 450vs. H NMR (400 MHz, d6-dmso): δ 8.90 – 8.84 (m, 1H), 8.30 (d, J
=
6.9 Hz, 1H), 8.18 (m, 4H), 7.87 (m, 5H), 7.73 (t, J = 7.9 Hz, 1H), 7.27 (d, J = 8.0 Hz, 1H),
+
7
1
4
.16 (d, J = 4.0 Hz, 1H), 6.56 (d, J = 4.0 Hz, 1H). ESI MS: m/z 1,279 [M – Cl] (15 %, calc.
,277.98), 479 (base peak, ligand). Anal. calc. for C H Br Cl N Pd S : C, 49.38; H, 2.30; N,
5
4
30
2
4
4
2 2
.27; S, 4.88 %. Found: C, 49.26; H, 2.29; N, 4.12; S, 4.72 %. Crystals of Pd1.acn self-
o
-1
assembled in acetonitrile. Mp. (with decomposition) 346 C. Selected IR peaks (ATR, cm ): ν
062m, 2918m, 2332m (CH CN), 2249m (CH CN), 1594s, 1496vs, 705vs, 451vs. Anal. calc.
3
3
3
for C H BrC N PdS: C, 50.40; H, 2.86; N, 7.58; S, 4.34 %. Found: C, 50.76; H, 2.85; N,
3
1
21
l2
4
7
.49; S, 4.24 %.
µ-(Pd2) : Ligand 2 (80 mg, 0.18 mmol), PdCl (CH CN) (46 mg, 0.18 mmol) gave µ-
2
2
3
2
o
-1
(
Pd2) (100 mg, 91 %). Mp. (with decomposition) 356 C. Selected IR peaks (ATR, cm ): ν
2
1
3
1
062m, 1594s, 1496vs, 765vs, 712vs. H NMR (400 MHz, d6-dmso) δ 8.90 (d, J = 8.4 Hz,
H), 8.85 (d, J = 8.3 Hz, 1H), 8.61 (dd, J = 7.9, 1.2 Hz, 1H), 7.88 – 7.74 (m, 6H), 7.71 – 7.64
(m, 1H), 7.54 (dd, J = 11.3, 4.1 Hz, 1H), 7.32 (t, J = 7.7 Hz, 1H), 7.12 (d, J = 4.0 Hz, 1H), 7.05
+
(
d, J = 7.6 Hz, 1H), 6.48 (d, J = 4.0 Hz, 1H). ESI MS: m/z 1,230 [M – Cl] (10 %, calc.
1
4
,228.94), 457 (base peak, ligand). Anal. calc. for C H Br Cl N Pd S : C, 47.46; H, 2.39; N,
50 30 2 4 4 2 2
.43; S, 5.07 %. Found: C, 47.07; H, 2.33; N, 4.41; S, 5.06 %. Pd2.acn crystals self-assembled
o
-1
in acetonitrile. Mp. (with decomposition) 283 C. Selected IR peaks (ATR, cm ): ν 3060m,
2
916m, 2340m (CH CN), 2313m (CH CN), 1594s, 1495vs, 700vs. Anal. calc. for
3
3
1
0

C H BrCl N PdS: C, 48.13; H, 2.69; N, 6.24; S, 4.76 %. Found: C, 48.40; H, 2.69; N, 6.14;
2
7
18
2
3
S, 4.80 %. Pd2.dmf was also isolated by allowing 2 and PdCl (CH CN) to stand in
2
3
2
o
-1
dimethylformamide (dmf). Mp. 112 C. Selected IR peaks (ATR, cm ): ν 3062m, 2962m,
655vs (carbonyl of dmf), 1594m, 1389s, 1093s, 766vs, 707vs. Anal. calc. for
C H BrCl N OPdS.2dmf.H O: C, 46.94; H, 4.40; N, 8.15; S, 3.69 %. Found: C, 46.39; H,
1
2
8
22
2
3
2
4
.47; N, 8.58; S, 3.29 %.
Pd3 : Ligand 3 (115 mg, 0.22 mmol) and PdCl (CH CN) (15 mg, 0.11 mmol)
2
2
3
2
o
-1
produced Pd3 (83 %). Mp. 360 C. Selected IR peaks (ATR, cm ): ν 3062m, 2932m, 2331w
2
(
CH CN), 2248w (CH CN), 1659vs, 705s. NMR (600 MHz, d6-dmso) δ 8.90 (d, J = 8.3 Hz,
3 3
1
7
H), 8.86 (d, J = 8.4 Hz, 1H), 8.62 (dd, J = 7.9, 1.1 Hz, 1H), 7.76 (dd, J = 11.0, 4.0 Hz, 1H),
.71 – 7.66 (m, 1H), 7.59 – 7.53 (m, 1H), 7.45 – 7.38 (m, 1H), 7.32 (d, J = 1.1 Hz, 2H), 7.20
(d, J = 7.5 Hz, 1H), 7.17 (d, J = 4.0 Hz, 1H), 6.65 (d, J = 4.0 Hz, 1H), 3.96 (s, 3H), 3.74 (s,
+
3
H). ESI MS: m/z 1172 [M – Cl] (35 %, Calc. 1,1172.72), 516 (base peak, ligand). Anal. calc.
for C H Br Cl N O PdS .½CH CN: C, 53.76; H, 3.24; N, 5.13; S, 5.22 %. Found: C, 53.99;
5
4
38
2
2
4
4
2
3
H, 2.85; N, 5.19; S, 5.74 %.
µ-(Pd4) : Ligand 4 (71 mg, 0.2 mmol) and PdCl (CH CN) (40 mg, 0.2 mmol) were
2
2
3
2
o
stirred in ethanol to produced µ-(Pd4) (90 mg, 90 %). Mp. 312 C. Selected IR peaks (ATR,
2
-1
cm ): ν 3071m, 2928m, 1658vs, 1514s, 1247vs, 756vs, 708vs. NMR (400 MHz, d6-dmso) δ
.87 (dd, J = 18.9, 8.3 Hz, 2H), 8.63 (d, J = 7.9 Hz, 1H), 7.76 (t, J = 7.4 Hz, 1H), 7.70 – 7.64
m, 1H), 7.61 (dd, J = 5.1, 1.0 Hz, 1H), 7.55 (t, J = 7.6 Hz, 1H), 7.40 (dd, J = 4.5, 2.7 Hz, 2H),
8
(
7
3
4
.29 (d, J = 3.2 Hz, 2H), 7.21 (d, J = 8.3 Hz, 1H), 7.03 (dd, J = 5.0, 3.8 Hz, 1H), 6.89 (dd, J =
+
.7, 0.9 Hz, 1H), 3.95 (s, 3H), 3.73 (s, 3H). ESI MS: m/z 979 [M – 2Cl] (45 %, calc. 978.15),
36 (100 %, ligand). Anal. calc. for C H Cl N O Pd S: C, 52.83; H, 3.28; N, 4.56; S, 5.22
5
4
40
4
4
4
2
1
1

o
%
. Found: C, 53.49; H, 3.45; N, 4.65; S, 5.28 %. Pd4 was self-assembled in dmf. Mp. 312 C.
2
-1
Selected IR peaks (ATR, cm ): ν 3071m, 2928m, 1658vs, 1514s, 1247vs, 756vs, 708vs. Anal.
calc. for C H Cl N O PdS .3dmf: C, 59.60; H, 4.84; N, 7.72; S, 5.05 %. Found: C, 59.44; H,
5
4
40
2
4
4
2
4
.58; N, 7.37; S, 4.94 %.
µ-(Pd5) : Ligand 5 (83 mg, 0.22 mmol) and PdCl (CH CN) (60 mg, 0.22 mmol)
2
2
3
2
produced orange-coloured µ-(Pd5) with two molecules of co-crystallized CHCl according to
2
3
o
-1
elemental analyses (120 mg, 92 %). Mp. 323 C. Selected IR peaks (KBr, cm ): ν 3070m,
595m, 1454s, 851s, 755vs, 704vs. NMR (600 MHz, d6-dmso) δ 8.90 (d, J = 8.3 Hz, 1H), 8.85
d, J = 8.4 Hz, 2H), 8.64 (dd, J = 7.9, 1.1 Hz, 1H), 7.79 – 7.77 (m, 3H), 7.70 – 7.65 (m, 1H),
1
(
7
1
.61 (dd, J = 5.0, 1.0 Hz, 1H), 7.58 – 7.50 (m, 1H), 7.35 – 7.28 (m, 1H), 7.06 (d, J = 7.6 Hz,
H), 6.99 (dd, J = 5.0, 3.8 Hz, 1H), 6.71 (dd, J = 3.7, 1.0 Hz, 1H). ESI MS: m/z 1172 [M –
Cl]+ (35 %, Calc. 1,1172.14), 376 (base peak, ligand). Anal. calc. for
C H Cl N Pd S .2CHCl : C, 46.39; H, 2.55; N, 4.16; S, 4.76 %. Found: C, 46.57; H, 2.75;
5
0
32
4
4
2
2
3
o
N, 4.18; S, 4.75 %. Pd5.acn was prepared in acetonitrile. Mp. 289 C (with decomposition).
-1
Selected IR peaks (ATR, cm ): ν 3078m, 2961m, 1664vs, 1596s, 1514vs, 1247vs, 1023vs,
20vs, 428vs. Anal. calc. for C H Cl N PdS: C, 54.52; H, 3.22; N, 7.06; S, 5.39 %. Found:
7
2
7
19
2
3
C, 54.85; H, 3.20; N, 7.33; S, 5.32 %. Pd5.dmf was also isolated from allowing
o
-1
PdCl (CH CN) and 5 to stand in dmf. Mp. 221 C. Selected IR peaks (ATR, cm ): ν 3072m,
2
3
2
2
3
927m, 1639vs, 1517s, 1360s, 706vs, 428vs. Anal. calc. for C H Cl N OPdS: C, 53.65; H,
28 23 2 3
.70; N, 6.70; S, 4.77 %. Found: C, 53.55; H, 3.76; N, 7.15; S, 4.77 %.
µ-(Pd6) : Ligand 6 (60 mg, 0.19mmol) and PdCl (CH CN) (50 mg, 0.19mmol)
2
2
3
2
o
-1
produced µ-(Pd6) (3 mg, 33 %). Mp. 297 C. Selected IR peaks (ATR, cm ): ν 3202s (br),
2
1
3
070m, 2921w, 1594s, 15.06s, 765s, 602vs. H NMR (300 MHz, d6-dmso) δ 13.49 (d, J = 15.8
1
2

Hz, 2H), 7.86 (m, 4H), 7.57 (d, J = 6.6 Hz, 2H), 7.44 (m, 4H), 7.35 (s, 12H), 7.00 (d, J = 15.0
+
Hz, 2H), 2.62 (d, J = 11.6 Hz, 6H). ESI MS: m/z 987 [M] (5 %, Calc. 987.89), 951 (– Cl), 496
(
monomer, 100 %), 317 (ligand). Anal. calc. for C H Cl N Pd S .2H O: C, 46.94; H, 3.55;
40 32 4 4 2 2 2
N, 5.47; S, 6.26 %. Found: C, 46.85; H, 3.18; N, 5.57; S, 5.73 %.
µ-(Pd7) : Ligand 7 (200 mg, 0.5 mmol) and PdCl (CH CN) (136 mg, 0.5 mmol) gave
2
2
3
2
o
-1
µ-(Pd7) (201 mg, 67 %). Mp. 343 C. Selected IR peaks (ATR, cm ): ν 3203s(br), 3069m,
2
1
2
1
6
921s, 1594s, 1575s, 1455s, 690vs. H NMR (400 MHz, d6-dmso): δ 13.74 (d, J = 22.5 Hz,
H), 7.93 (d, J = 7.3 Hz, 1H), 7.85 (d, J = 6.7 Hz, 1H), 7.53 – 7.44 (m, 4H), 7.42 – 7.33 (m,
+
H). ESI MS: m/z 1117 [M] (5 %, Calc. 1117.67), 520 (monomer – Cl, 100 %), 381 (ligand).
Anal. calc. for C H Br Cl N Pd S : C, 40.85; H, 2.35; N, 5.01; S, 5.74 %. Found: C, 41.33;
3
8
26
2
4
4
2 2
H, 2.35; N, 5.08; S, 5.70 %. Pd7.acn was obtained by self-assemble of ligand 7 and
o
PdCl (CH CN) in acetonitrile. Mp. 329 C (with decomposition). Selected IR peaks (ATR,
2
3
2
-1
cm ): ν 3202s (br), 3069m, 2921m, 2851w, 2324w (CH CN), 1593s, 1498s, 692vs. ESI MS:
3
+
m/z 559 [M – Cl] (10 %), 521 (– 2Cl, 100 %), 381 (ligand). Anal. calc. for
1
C H BrCl N PdS.H O. / CH CN: C, 41.12; H, 3.01; N, 7.25; S, 5.11 %. Found: C, 41.67; H,
2
1
16
2
3
2
4
3
2
.94; N, 7.24; S, 4.86 %.
Pd8 : Ligand 8 (72 mg, 0.2 mmol) and PdCl (CH CN) (26 mg, 0.1 mmol) stood in
2
2
3
2
dmf to give crystals of Pd8 (65 mg, 72 %). NMR: Solubility in deuterated solvents was bad.
2
+
ESI MS: m/z 865 [M – Cl] (20 %, Calc. 865.09), 830 (100 %, – 2Cl), 363 (ligand). Anal. calc.
for C H Cl N O PdS .2dmf: C, 54.99; H, 4.81; N, 8.02; S, 6.12 %. Found: C, 55.13; H, 4.78;
4
2
36
2
4
4
2
N, 8.14; S, 6.00 %.
1
3

Pd9.acn: Ligand 9 (100 mg, 0.3 mmol) and PdCl (CH CN) (87 mg, 0.3 mmol) self-
2
3
2
o
1
assembled to give crystals of Pd9.acn (0.14 g, 83 %). Mp. 170 C H NMR (300 MHz, d6-
dmso): δ 8.09 (dd, J = 6.3, 2.7 Hz, 2H), 7.69 – 7.62 (m, 4H), 7.59 – 7.53 (m, 3H), 7.51 – 7.38
+
(
m, 6H), 2.05 (s, 3H, acetonitrile). ESI MS: m/z 481 [M – Cl] (18 %, calc. 480.28), 443 (M –
2
5
Cl), 299 (ligand). Anal. calc. for C H Cl N OPd: C, 53.57; H, 3.52; N, 5.43 %. Found: C,
23 18 2 2
3.13; H, 3.54; N, 5.90 %.
Pd10 : Ligand 10 (65 mg, 0.2 mmol), PdCl (CH CN) (45 mg, 0.2 mmol) were reacted
2
2
3
2
as for µ-(Pd1) above, but with only ethanol as solvent to obtain Pd10 as orange powder (20
2
2
o
-1
mg, 66 %). Mp. 320 C. Selected IR peaks (ATR, cm ): ν 3067m, 2847w, 2768w, 1583s,
1
1
1
553s, 1454vs, 1129s, 765vs, 696vs. H NMR (300 MHz, d6-dmso): δ 14.01 (s, 1H), 13.17 (s,
H), 8.09 (dd, J = 15.9, 6.3 Hz, 2H), 8.00 – 7.88 (m, 2H), 7.84 (t, J = 7.8 Hz, 2H), 7.64 – 7.55
+
(
m, 2H), 7.49 (m, 6H), 7.38 (d, J = 3.4 Hz, 8H), 7.30 (s, 4H). MS (EI) m/z 556 (M , 100 %):
5
56, 778, 660, 587, 515, 351, 297. Anal. calc. for C H Br Cl N Pd.3H O: C, 48.83; H, 3.48;
40 28 2 2 6 2
N, 8.54 %. Found: C, 48.88; H, 2.92; N, 8.36 %.
Single crystal X-ray data
The intensity data for the compounds were collected on a Nonius KappaCCD
diffractometer using graphite-monochromated Mo-K radiation. Data were corrected for

Lorentz and polarization effects; absorption was taken into account on a semi-empirical basis
using multiple-scans.[41–44] The structures were solved by direct methods (SHELXS) and
2
refined by full-matrix least squares techniques against Fo (SHELXL-97).[44] The hydrogen
atoms of the compounds Pd1.acn (with exception of the methyle group of C29), Pd5.acn, and
the hydrogen atoms bonded to the imidazole N of Pd8.acn, Pd8 , and Pd10 were located by
2
2
difference Fourier synthesis and refined isotropically. All other hydrogen atoms were included at
1
4

calculated positions with fixed thermal parameters. All non-hydrogen and non-disordered atoms
were refined anisotropically.[44] Pd8.acn crystallizes as non-merohedral twins.[45] The twin
law is -1 0 0 0 -1 0 0.441 0.139 1. The fractional contribution of the minor component refined
to 0.145(2). The program XP[46] and DIAMOND[47] was used for structure representations.
Catalysis experiments and characterization of biphenyl products
Except for the few higher temperature catalysis experiments, which were carried out
under reflux conditions, the ambient condition catalysis runs were routinely conducted in
o
sealed glass vials maintained at 40 – 50 C by thermostated oil baths equipped with magnetic
stirrers. The substrates boronic acid (1 mmol) and arylbromide reagents (1 mmol) were coupled
in the presence of a base additive (1.2 eq.) and palladium catalyst material (0.2 mol %) using
water / ethanol mixture (1:3) as reaction media. After the desired duration, an aliquot of the
resultant reaction mixture is transferred to a clean vial. The solvent mixture is evaporated under
high vacuum suction pressure with cooling trap in place after which the residue is collected in
deuterated dmso and transferred into an NMR tube. Yields were routinely estimated by
comparison of the NMR signal of the methylene functions on bromophenymethanol and that
on the biphenyl coupling product. The catalysis product 1-(4'-(hydroxymethyl)-[1,1'-
biphenyl]-4-yl)ethan-1-one has been isolated and characterized.[28] Other new catalysis
+
products were also analysed: 4-(4-methoxyphenyl)pyridine: EI MS: m/z 185 [M] (100 %, calc.
1
85.23), 108 (anisyl), 78 (pyridyl). 4'-methoxy-[1,1'-biphenyl]-2-amine: EI MS: m/z 199 [M]+
(100 %, calc. 199.25), 184 (-methyl). 4,4'-dimethoxy-[1,1'-biphenyl]-2-carboxylic acid: EI
+
MS: m/z 258 [M] (100 %, calc. 258.27), 241 (-hzdrodxy), 213 (-carboxy), 152, 106 (anisyl).
+
4
-(benzyloxy)-4'-methoxy-1,1'-biphenyl: EI MS: m/z 290 [M] (100 %, calc. 290.36), 199 (-
+
benzyl), 91 (-benzyl). 4,4'-dimethoxy-3-nitro-1,1'-biphenyl: EI MS: m/z 259 [M] (100 %, calc.
2
59.26), 244 (-methyl), 214 (-nitro), 198 (-methyl and nitro), 183 (- 2 methyl and nitro), 168.
1
5

+
(
3',5'-dimethyl-[1,1'-biphenyl]-4-yl)methanol: EI MS: m/z 212 [M] (100 %, calc. 212.29), 195
(-hydroxy), 183 (- 2methyl).
Estimation of ligand N-donor strength
Typically, protonation equilibrium constant determinations were spectroscopically
-5
carried out by UV-Vis or fluorescence measurements using 10 M solutions of the compounds
in ethanol-water mixture (70 % absolute EtOH and 30 % H O). A calculated amount of
2
potassium chloride was used to maintain fairly constant ionic strength of 0.1 M. Adjustment of
the pH value of the solutions was achieved through the addition of minute volumes of
potassium hydroxide or hydrochloric acid solutions and monitored with the aid of Mettler
Toledo MPc227 pH/Conductivity Meter calibrated by buffers at pH values of 4.0, 7.0 and 10.1.
Results and discussions
Syntheses of ligands and palladium(II) complexes
The deployment of several ligands (Scheme 2 (a)) is with the hope of possibly learning
influence of structure-property correlations on the catalytic outcomes. Complexes were also
deliberately prepared from various solvent media in order to enable isolating of palladium
species in diverse coordination environments. The isolated palladium complexes can be
grouped into three variants, which are the mono-ligand complexes that are complemented by
coordinated solvent (i.e. Scheme 2 (b), PdL.acn and PdL.dmf), the mono-ligand complexes
that formed Cl-bridged dimers due to absence of coordinating solvent (i.e. Scheme 2 (c), µ-
(
PdL) ) and the bis-ligand complexes (i.e. Scheme 2 (d), PdL ). Coordinated as well as co-
2
2
crystallized, non-coordinated solvents were evidenced by X-ray data as well as by their non-
stoichiometric amounts in the analytical data of the dried samples. While coordinating solvents
1
6

like acetonitrile and dmf generally enabled assembly of the mono-ligand complexes PdL.acn
and PdL.dmf by acting as co-ligands, complexation reactions in poorly coordinating solvents
like ethanol generally lead to the chlorido-bridged coordination products µ-(PdL) . However,
2
some reactions in dmf also yielded bis-ligand complexes (Pd4 and Pd8 ) [48] while all the
2
2
methoxy-substituted ligands 3, 4 and 8 participated in forming the bis-ligand PdL species
2
even when 3 was reacted in acetonitrile under the stoichiometry of 1:1.
(a) Ligands
O
O
O
O
Br
O
Br
N
N
S
Br
N
N
S
S
S
S
N
N
N
N
N
S
N
3
N
4
1
2
5
H
Br
Br
N
S
N
HN
S
O
HN
HN
N
N
N
N
6
7
9
10
8
O
(b) Mono-ligand complexes
(c) Cl-bridged mono-ligand
(d) trans-Bis-ligand complexes
Cl
L
Cl
L
Cl
L
Cl
L
Cl
Pd Pd
I
Ph3P
I
Pd
Pd
Pd
Pd
Cl
L
Cl
L
Cl
acn
Cl
dmf
Cl
-(Pd1)2
-(Pd2)2
PPh3
PdI (PPh )
2 3 2
Pd1.acn
Pd2.acn
Pd5.acn
Pd7.acn
Pd8.acn
Pd9.acn
Pd32
Pd5.dmf
Pd2.dmf
Pd42
Pd82




-(Pd4)2
-(Pd5)2
-(Pd6)2
-(Pd7)2
Pd102
Scheme 2: (a) The investigated ligand frameworks: 2-(thiophen-2-yl)-1H-imidazoles 1 – 8,
,4,5-triphenyl-1H-oxazole 9 and 2-(1H-imidazol-2-yl)pyridine 10. (b) Mono-ligand
2
complexes, (c) mono-ligand Cl-bridged complexes and (d) trans-bis-ligand complexes
Single crystal structures
Fig. 1 presents structures for complexes Pd1.acn, Pd5.acn and Pd8.acn while
structures of some of the trans-bis-ligand complexes Pd8 , Pd10 and PdI (PPh ) are
2
2
2
3 2
1
7

displayed in Fig. 2. Structure refinement details are summarized in Table 1 while selected bond
properties, which are within expected value range,[27,29,49] are collected in Table 2.
Structures for complexes Pd2.acn, Pd7.acn and Pd9.acn as well as structures of some free
ligands were also obtained and presented in the Supplementary Information Fig. S1 and Fig.
S2.
It is notable that the Pd–N bond lengths for the bis-ligand PdL species are slightly
2
longer than for the mono-ligand PdL.acn analogues, which suggests probable presence of
ligand-ligand steric repulsion in the bis-ligand analogues or influence of trans-ligand effects
(Table 2, (b) versus (a)). Furthermore, the relative thiophene ring twists away from coplanarity
with the imidazole rings, which are larger for the palladium(II) complexes of the
o
o
o
phenanthreneyl-substituted ligands (e.g. Pd1.acn = 49 , Pd2.acn = 47 and Pd5.acn = 75 )
o
o
o
than for those of the 4,5-diphenyl-substituted ligands (e.g. Pd7.acn = 6 or 4 , Pd8.acn = 3 or
o
o
1
7 and Pd9.acn = 14 ), indicate that the phenanthreneyl ligands are the more rigid and
sterically demanding ligands. Structure overlays, which were obtained by superimposition of
the imidazole ring atoms (C1-N1-C2-C3-N2), illustrate the comparative extents of loss of
coplanarity for the complexes relative to the almost complete coplanarity observed in free
ligands (Fig. 3, see Supplementary Information Fig. S2). In summary, rigid and bulky fused-
ring ligands are generally favourable for formation of the mono-ligand complexes PdL.acn or
PdL.dmf and their trans-bis-ligand coordination products (e.g. Pd3 and Pd4 ) can viewed as
2
2
being more susceptible to dissociation owing to ligand-ligand repulsion.
Continuous Shape Measure calculations (CShM) were carried out on the presented
structural geometries to quantitatively analyse the degrees of deviation of the distorted square
planer coordination environments from an ideal square planar polyhedron. The results
generally indicate minimal deviations with values ranging from 0.279 % to 0.561 % deviations
1
8

and the bis ligand complexes displayed slightly lower values relative to the mono-ligand
complexes (Table S2).
Fig. 1: Structures of complexes Pd1.acn, Pd5.acn and Pd8.acn with thermal ellipsoids drawn
at the 50 % probability level. Some protons and non-coordinated solvent molecules have been
omitted for clarity.
1
9

Fig. 2: Structures of complexes Pd8 , Pd10 and PdI (PPh ) with thermal ellipsoids drawn at
2
2
2
3 2
the 50 % probability level. Some protons and non-coordinated solvent molecules have been
omitted for clarity. Hydrogen bonds are shown as dotted bonds.
2
0

Fig. 3: Structure overlays; the left shows significant thiophene ring twists for Pd1.acn and
Pd2.acn relative to Pd5.acn, but the right shows lower twist in Pd8.acn compared to Pd5.acn
(Note: The N-donor labelled N1 in the left overlay represents the N2 atom of Pd1.acn and vice
versa).
Table 1: Crystal data and refinement details for the X-ray structure determinations.
Parame
ters
Pd1.acn
Pd5.acn
Pd8.acn
PdI (PPh
2
Pd82
Pd102
3)2
Formula C H BrCl
C H Cl
C H Cl N
C H Cl N
C H Br Cl
C H I O
40 38 2
31
21
2
27 19
2
28 28.5
2
5.
48 50
2
6
46 42
2
2
N PdS
4
N PdS
3
O PdS
O PdS
N O Pd
P2Pd
5
2
6
2
8
2
fw
g∙mol )
7
38.79
594.81
683.42
-140(2)
triclinic
1048.36
-140(2)
1076.00
-140(2)
956.84
-1
(
T (°C)
crystal
system
space
group
a/ Å
-140(2)
-140(2)
orthorhom
bic
-140(2)
monoclini
c
monoclinic
monoclinic
C 2/c
monoclinic
P 2 /n
P b c a
P ī
P 2 /n
C 2/c
1
1
12.2594(5
7
.6102(1)
9.2523(2)
14.4051(6)
14.4176(5)
14.9400(5)
27.3423(7)
9.8928(3)
35.5710(9)
13.2553(2)
9.5124(2)
17.8364(3)
)
b/ Å
c/ Å
14.9869(6
1
7.5506(4) 16.2106(3)
1.8658(3) 32.1392(6)
)
20.0824(6
2
)
90
91.470(2)
90
α/°
β/°
γ/°
90.00
98.4660(10)
90.00
90
90
90
92.259(2)
101.775(2)
97.4060(2)
90
95.826(1)
90
90
94.493(1)
90
3
V/Å
4820.41(1
2
888.65(9)
3005.30(19)
9572.0(5)
8
2242.08(7)
2
3688.5(2)
4
6)
Z
4
8
4
-
ρ (g∙cm
1
.699
23.12
0928
1.639
11
1.510
9
1.455
6.42
1.594
23.63
13429
1.723
22.94
9643
3
)
-1
µ (cm )
measure
d data
2
34536
30760
24412
data with
I > 2σ(I)
unique
data
5
783
5145
10382
9803
4597
3454
5
467/0.03
10787/0.026
9
4153/0.02
55
6538/0.0419
0.0713
13319/0.0657
5132/0.0262
0.1752
84
(
R )
int
wR (all
2
data, on
0.0622
0.1624
0.0759
0.1101
2
a
F )
R1 (I >
2
0.0311
0.0290
1.134
0.0710
1.076
0.0357
1.093
0.0579
1.075
0.0400
1.100
a
σ(I))
b)
S
1.087
Res.
0
0
.894/-
.604
1.367/-
1.161
dens./e∙
0.513/-0.537
2.078/-1.727
multi-scan
0.571/-0.774 2.143/-2.523
multi-scan multi-scan
-3
Å
absorpt
method
absorpt
corr
multi-
scan
multi-scan
multi-scan
0
.5886/0.74 0.6970/0.7
0.6455/0.745 0.6732/0.745 0.6009/0.
7456
0.6452/0.7456
56
456
6
6
T /
min max
2
1

CCDC
No.
1821350
1
821351
1821352
1821353
1821354
1821355
a
2
2 2
2 2 1/2
Definition of the R indices: R = (F -F )/F ; wR = {[w(F -F ) ]/[w(F ) ]}
1
o
2
c
o
2
o
c
2 2
o
-1
2
2
2
2
b)
2
1/2
with w = σ (F ) + (aP) +bP; P = [2F + Max(F ]/3; s = {[w(F -F ) ]/(N -N )} .
o
c
O
o
c
o
p
Table 2: Bond characteristics around the palladium metal centres of analysed structures
a) Mono-ligand trans-acetonitrile complexes
(
Complexes
Pd1.acn
Pd2.acn
Pd5.acn
Pd7.acn
Pd7.acn
Pd8.acn
Pd8.acn
Pd9.acn
Pd – N
Pd – Cl
Torsionc
49.05
47.31
75.04
6.39
1.999(2), 1.999(2) 2.304(1), 2.299(1)
2.016(2), 1.990(2) 2.305(1), 2.292(1)
2.005(2), 2.004(2) 2.302(1), 2.298(1)
1.983(2), 2.008(3) 2.300(1), 2.298(1)
1.999(2), 2.004(3) 2.325(1), 2.283(1)
1.986(5), 2.000(5) 2.308(2), 2.298(2)
1.994(5), 1.996(5) 2.309(2), 2.306(2)
2.001(2), 1.990(2) 2.300(1), 2.290(1)
a
a
b
4.32
3.01
17.52
13.89
b
a
(
b) Sterically hindered trans-bis-ligand complexes
Complexes
Pd82
Pd82
Pd – N
Pd – Cl
Torsionc
25.01
2.025(2), 2.025(2) 2.307(1), 2.307(1)
2.044(2), 2.044(2) 2.283(1), 2.306(1)
b
13.53
Pd102
2.024(4), 2.024(4) 2.305(1), 2.303(1)
47.19
a
b
Structure presented in the Supporting Information Fig. S1. Data belong to second crystallographically
independent molecule in unit cell. The measure of relative twist of the azole and thiophene rings.
c
Ligand donor strengths
Knowledge of the ligand N-donor strengths were also pursued in order to obtain probable
insight into how they influence electrophilicity of the palladium metal centres, their possible influence on
the coordination characteristics and correlation with catalytic trends of the resulting complexes. Using the
-
Henderson-Hasselbalch approximation (Eqn. 1), which becomes simplified to pH = pK when [A ] is equal
a
to [HA], spectroscopic analyses of the protonation-deprotonation equilibrium (Scheme 3) enabled
estimation of ligand N-donor strengths by focusing on the conjugate acids of the ligands. Fig. 4 exemplifies
the stacked spectra for ligands 3 (left) and 4 (right) with isosbestic features. It is noteworthy that
fluorescence measurements are helpful in situations where the UV-Vis spectral profiles are not good enough
as for the 4,5-diphenyl-substituted ligands 6 – 8. The estimated ligand pK values are listed in Table 3 (see
a
Supplementary Information Fig. S3 for complete spectral stack presentations).
2
2

퐴 ―
]
[
푝퐻 = 푝퐾 + 푙표푔
(1)
푎
10([퐻퐴])
The estimated pK values for the rigid pyreneyl / phenanthreneyl ligands 1–5 (pK = 1.5 – 2.4)
a
a
generally suggest weaker N-donor strengths compared to their 4,5-diphenylimidazole analogues 6–8 (pKa
2.7 – 4.7) (Table 3). Since our previous results[36] suggest that substitution at the 1H-imidazole proton
=
does not significantly influence N-donor strengths, the observed difference can be attributed to stronger
delocalization of electrons in the phenanthreneyl rings. Within ligands 1–5, the electron-withdrawing
influence of the distant bromo-substituent of ligands 1–3 appear to be responsible for their lower pK s (1.5
a
–
1.9).[38] However, replacement of the imidazole NH group by oxygen as in the oxazole ligand 9
significantly reduces donor strength (i.e. pK ≤ 0.8 for the oxazole 9).[28,36] Furthermore, it could also be
a
concluded that weaker ligand donor strengths appear to support formation of mono-ligand coordination
products then the trans-bis-ligand complexation. The significantly weaker donor strengths of the studied
ligands relative to the phosphine ligands is also noted.
R
R
+
R'
N
+
H
R'
N
S
S
protonation
N
N
H
deprotonation
+
-
H
R = H or Br
R' = H or Ph derivatives
Scheme 3: A generalized protonation-deprotonation equilibrium at the N-donor of the studied compounds
2
3

Fig. 4: Representative stacked absorption spectra of ligand 3 and emission spectra of ligand 4 during
protonation-deprotonation equilibria. Insets show sigmoid fittings for plots of absorption or emission
2
2
intensities against pH (3, R = 0.9908; 4, R = 0.9998).
Table 3: The pK estimates of studied ligands
a
Ligands pK of conjugate acids
a
1
2
3
4
1.68 ± 0.08
1.52 ± 0.05
1.90 ± 0.09
2.43 ± 0.01
2.10 ± 0.02
a
5
a
a
a
a
6
7
8
9
4.65 ± 0.13
3.50 ± 0.03
2.67 ± 0.10
0.84 ± 0.08
+
b
HPPh3
7.65
a
b
These pK estimations were done by using fluorescence emission spectra. Data obtained from
a
literature.[50]
Selecting catalytic setting for the complexes
The primary objectives of the catalysis experiments are (i) to study influence of the various
coordination environments on coupling catalysis at low temperatures and (ii) to study of influence of ligand
differences on the desired catalysis outcomes. Therefore, preliminary catalytic runs were carried out in
order to establish a set of reaction conditions to which all the precatalysts would be comparatively subjected.
Using 1.0 mmol arylbromide, 1.0 mmol arylboronic acid, 1.2 mmol base additive and 0.2 mol % catalyst
material in 4 mL of 3:1 ethanol / water reaction media, the results of catalytic behaviours under varying
2
4

conditions were collected using randomly picked members of the palladium precatalyst series and are
presented in Table 4.
o
o
o
Firstly, after 60 minutes of stirring at temperatures of 20 C, 30 C and 40 C in the presence of the
chlorido-bridged, mono-ligand complex µ-(Pd2) , it was established that the catalyst becomes active from
2
o
about 40 C (entries 1 – 3, Table 4). In terms of the temperature regime, such ambient temperature
performance is a very significant improvement relative to reported performances by the trans-bis-ligand
complexes of monodentate N-donors[31–35] as well as performances by the bidentate 2-(1H-imidazol-2-
o
yl)pyridines[27] and 2-(1H-imidazol-2-yl)phenols all of which begin to be active from about 90 C
(Scheme 1 (c)).[28,29] Experiments were conducted to further compare temperature-dependence of the
catalytic performance within 5 minutes durations for the mono-ligand complexes µ-(Pd1) , µ-(Pd2) and
2
2
µ-(Pd4) and the results show a similar temperature profile of yield increase versus temperature rise for the
2
o
three complexes. A steep yield rise around 50 C is observed for the three complexes (Fig. 5 (a)), which
suggests that quantitative conversions may be achieved in much lesser than 5 minutes if higher temperatures
o
were deployed. Further reactions conducted at 45 C also show increasing yields with increasing reaction
times is illustrated by Fig. 5 (b), which indicates that the active species are living.
Secondly, positive ligand effect could be established for only the preformed complex µ-(Pd1) (48
2
%
) since the in situ ‘ligand 1 + PdCl (CH CN) ’ approach gave the same 16 % yield as when only the
2 3 2
palladium(II) salt PdCl (CH CN) was deployed. With K CO as a better base (entries 7 – 11, Table 4), it
2
3
2
2
3
o
was decided to continue the further reactions at 45 C and 60 minutes.
Table 4: Results for catalytic performance in the presence of 0.2 mol % of randomly selected pre-catalyst
a
analogues under varying reaction conditions
[
Pd]
O
HO
O
HO
+
(HO) B
2
EtOH/H O
Br
2
(3:1)
o
Time (min.) Yield (%)b
Entry Catalyst material
Temp. ( C) Base
1
2
3
µ-(Pd2)2
µ-(Pd2)2
µ-(Pd2)2
20
30
45
K CO
60
60
60
3
4
43
2
3
3
3
K CO
2
K CO
2
2
5

4
5
6
7
8
9
1
1
PdCl (CH CN)
40
K CO
150
150
150
60
60
60
16
16
48
59
Nill
4
2
3
2
2
3
3
3
3
1 + PdCl (CH CN) 40
K CO
2
3
2
2
µ-(Pd1)2
Pd5.acn
Pd5.acn
Pd5.acn
Pd5.acn
Pd5.acn
40
45
45
45
45
45
K CO
2
K CO
2
None
Et N
3
0
1
Cs CO 60
53
54
2
3
Na CO 60
2
3
a
Common reaction conditions: 1.0 mmol of (4-acetylphenyl)boronic acid; 1.0 mmol of (4-
bromophenyl)methanol; 0.2 mol % catalyst loading; 1.2 mmol base additive; Solvent media is 4 mL of 3:1
ethanol/H O mixture. Yields are estimated by H-NMR and reported to the nearest whole number.
b
1
2
(
b)
6
0
0
0
0
4
2
0
50
100
Time /min.
150
Fig. 5: (a) Catalyst activity change as a function of reaction temperature for µ-(Pd1) , µ-(Pd2) and µ-
2
2
o
(
Pd4) under 5 minutes; (b) Plot of reaction yield for µ-(Pd5) against reaction time at 45 C. Reaction
2
2
conditions: 1 mmol of both coupling partner substrates, 0.2 mol % catalyst, 1.2 eq. K CO .
2
3
Comparison of catalysis by coordination environments and ligand properties
In order to comparatively analyse influence of the different coordination modes and ligand
variations on catalytic outcomes under ambient temperatures, 1.0 mmol of both (4-acetylphenyl)boronic
acid and (4-bromophenyl)methanol, 0.2 mol % catalyst loading and 1.2 mmol K CO in 3:1 ethanol/H O
2
3
2
o
mixture (4 mL) were stirred at 45 C for 60 minutes. The catalysis results are shown in Fig. 6 as a bar chart
of turnover frequencies (TOFs) and the corresponding table of data is provided in Supplementary
Information Table S1. In our focus on monodentate N-donor ligands, three key conclusions could be drawn.
Firstly, the trans-bis-ligand pre-catalysts (i.e. PdL ) generally performed poorer than the mono-
2
ligand analogues (i.e. PdL.acn, PdL.dmf or µ-(PdL) ). While PdI (PPh ) , which is similar to the popular
2
2
3 2
o
phosphine-based coupling catalyst, offered no observable catalyst activity at 45 C temperature regime, the
2
6

bis-ligand complexes Pd8 and Pd10 gave only 13 % and 6 % yields, respectively (Fig. 6, Table S1). The
2
2
higher TOF values obtained for the bis-ligand complexes Pd3 and Pd4 could be attributed to their ease
2
2
of decomposing into mono-ligand species, which is consequent on ligand-ligand repulsions between the
bulky and weakly donating phenanthreneyl ligands. That the PdL systems could generate active species
2
at all while PdI (PPh ) generates none is arguably attributable to the much stronger donor strength of the
2
3 2
triphenylphosphine ligand. Therefore, it could be concluded that (i) the trans-bis-ligand coordination
remarkably hinders ambient temperature generation of active palladium centres and that (ii) the stronger
the donor strength of monodentate ligands in trans-bis-ligand complexation, the worse the chances of
functioning as a catalyst for the ambient temperature regimes becomes.
Secondly, comparing among the catalytically productive mono-ligand complexes PdL.acn,
PdL.dmf and µ-(PdL) in Fig. 6, complexes of the flexible 4,5-diphenyl-substituted ligands displayed
2
relatively weaker efficiencies (i.e. Pd7.acn, Pd8.acn and Pd9.acn compared to Pd1.acn – Pd5.acn; µ-
(
Pd6) and µ-(Pd7) compared to µ-(Pd1) - µ-(Pd5) ). Therefore, rigidity or bulkiness of the ligand
2 2 2 2
frameworks appears to be important for the low temperature catalysis. The highest TON value observed
from the complexes of ligand 5 (i.e. Pd5.acn and µ-(Pd5) ) may probably be associated with the larger
2
extent of out of plane thiophene ring twist.
Thirdly, acetonitrile as complementary ligand appears more favourable for active catalyst
generation than dmf or the chlorido-bridging coordination. In summary, the ambient temperature
performance can be considered successful for the mono-ligand dihalopalladium(II) complex designs
supported by monodentate N-donor ligand and complemented by an easily detachable solvent co-ligand.
On the other hand, the use of more than 1:1 ligand equivalents in palladium catalysis, which can be viewed
as imparting negative influence on the catalytic behaviour of palladium centre, should be avoided if ambient
temperature catalyst reactivities is desired.[51] As outlook, the design of strongly coordinating N-donors
with steric features capable of hindering bis-ligand complexation may be the way to go for designing N-
supported palladium precatalysts. Scheme 4 presents results that generally indicate substituent tolerance.
2
7

However, while single ortho-substituted aryl bromide was easily coupled, the 2,6-disubstituted aryl
bromide yielded negligible coupling products. Trace of activated aryl chloride coupling was also observed
o
at 60 C by complex Pd1.acn (see also Fig. S4 of the Supplementary Information).
a
Fig. 6: Catalytic performance for the series of precatalyst probe complexes. Reaction conditions: 1 mmol
of (4-acetylphenyl)boronic acid; 1 mmol of (4-bromophenyl)methanol; 1.2 equivalent of K CO ; 0.2 mol
2
3
o
b
%
of palladium complex loading; Solvent media, 4 mL of 3:1 solvent/H O mixture.; 45 C; 1hr. Yield
2
1
determined by H-NMR spectroscopy
2
8

O
CN
O
O
O
O
O
(c) 41 % (3 h, 40 C)a
o
o
a) 64 % (3 h, 40 C)a
o
(b) 77 % (3 h, 40 C)a
(
F
HO
HO
HO
O
O
(e) 62 % (3 h, 40 C)a
o
o
a
o
d) 62 % (3 h, 40 C)a
(f) Nill % (3 h, 40 C)
(
Ph
O
O
O
O
COOH
(h) Nill % (1 h, 45 C)
NH2
o
b
o
b
o
b
(i) 52 % (5 min, 45 C)
(
g) 67 % (1 h, 45 C)
o
b
7
6 % (1 h, 45 C)
O N
O
O
2
HO
O N
2
o
(l) 11 % (8 h, 60 C)c
o
b
o
b
(
j) 73 % (5 min, 45 C)
(k) 68 % (1 h, 45 C)
6 % (1 h, 45 C)b
o
8
(
m)b
O
S
o
O
1 h, 45 C
Br
+
HO
HO
Cl
Nill %
Scheme 4: Coupling reactions with various substrates (Reaction conditions: 1 mmol of boronic acid
reagent; 1 mmol of aryl bromide reagent; 1.2 equivalent of K CO ; 0.2 mol % of palladium complex
2
3
1
a
loading; Solvent media, 4 mL of 3:1 EtOH/H O mixture; Yield determined by H-NMR. Catalyzed by µ-
Pd1) ; Catalyzed by 0.2 mol % of Pd1.acn; Catalyzed by 1 mol % of Pd1.acn.)
2
c
b
(
2
Conclusions
Monodentate 2-(thiophen-2-yl)-1H-imidazoles 1 – 8, 2,4,5-triphenyloxazole 9 and 2-(1H-
imidazol-2-yl)pyridine 10 have been prepared to study N-donor ligand frameworks towards ambient
temperature functionality of palladium species in coupling catalysis. Their corresponding palladium
complexes were obtained in three coordination environments: (i) the mono-ligand PdL.acn or PdL.dmf
2
9