Flexible, N-sulfonyl-substituted aliphatic amine ligands in palladium-catalyzed Suzuki–Miyaura C–C coupling: Influence of substituents bulkiness and co-ligand size

Article abstract of DOI:10.1016/j.poly.2018.11.044

Widespread use of commercially available palladium precatalysts is limited by high costs and their synthetic challenges. In this report, series of synthetically affordable, phosphine-free ligands were examined as supports for palladium active centers. 2-(

Full text of DOI:10.1016/j.poly.2018.11.044

Accepted Manuscript
Flexible, N-sulfonyl-substituted aliphatic amine ligands in palladium-catalyzed
Suzuki-Miyaura C-C coupling: influence of substituents bulkiness and co-ligand
size
Hammed Olawale Oloyede, Joseph Anthony Orighomisan Woods, Helmar
Görls, Winfried Plass, Abiodun Omokehinde Eseola
PII:
S0277-5387(18)30769-1
https://doi.org/10.1016/j.poly.2018.11.044
POLY 13591
DOI:
Reference:
To appear in:
Polyhedron
Received Date:
Revised Date:
Accepted Date:
30 August 2018
31 October 2018
19 November 2018
Please cite this article as: H.O. Oloyede, J.A.O. Woods, H. Görls, W. Plass, A.O. Eseola, Flexible, N-sulfonyl-
substituted aliphatic amine ligands in palladium-catalyzed Suzuki-Miyaura C-C coupling: influence of substituents
bulkiness and co-ligand size, Polyhedron (2018), doi: https://doi.org/10.1016/j.poly.2018.11.044
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Flexible, N-sulfonyl-substituted aliphatic amine ligands in palladium-catalyzed
Suzuki-Miyaura C-C coupling: influence of substituents bulkiness and co-ligand
size
Hammed Olawale Oloyede,a,b Joseph Anthony Orighomisan Woods, Helmar Görls,
a
b
b,
b,c,
Winfried Plass, Abiodun Omokehinde Eseola
aInorganic Chemistry Unit, Department of Chemistry, University of Ibadan, Ibadan, Nigeria
bInstitut fꢀr Anorganische und Analytische Chemie, Friedrich-Schiller-Universitꢁt Jena,
Humboldtstraße 8, 07743 Jena, Germany
cMaterials Chemistry group, Department of Chemical Sciences, Redeemer’s University Ede,
Osun State, Nigeria
Abstract
Widespread use of commercially available palladium precatalysts is limited by high
costs and their synthetic challenges. In this report, series of synthetically affordable,
phosphine-free ligands were examined as supports for palladium active centers. 2-(2-
Aminoethylamino)ethanol, diethylenetriamine and tris(2-aminoethyl)amine were condensed
with sulfonyl chloride reagents in order to obtain flexible, aliphatic amine derivatives with
varied steric bulk at the chain ends (ligands 1-Me and 1-tol = RSO
CH CH Cl; ligands 2-ipr and 2-iprNH = RSO –NH–CH CH –NY–CH
Y is H or R; ligands 3-Me, 3-tol and 3-ipr = RSO –N(CH CH –NH–SO
; ligands 4-tol and 4-ipr = N(CH CH –NH–SO R)
2
–NH–CH
CH –O–SO
R) ; 3-iprNH =
; R = methyl,
2
CH
2
–N(SO
2
R)–
2
2
2
2
2
2
2
2
R where
2
2
2
2
2
HN(CH
2
CH
2
–NH–SO
2
R)
2
2
2
2
3

Corresponding authors: Dr. A. O. Eseola; Present Address:- Institut für Anorganische und Analytische Chemie, Friedrich-Schiller-Universität Jena,
Humboldtstr. 8, D-07743 Jena, Germany. Permanent address:-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

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

tolyl or triiso-propyl). Despite the flexibility of the alkyl fragments in these ligands,
placement of sterically demanding groups at amine donors enables formation of active
species, which supports high turnover frequencies and yields up to 91 % within 5 min and at
0
.2 mol % palladium loading. Such activity from synthetically simple alkyl ligand
frameworks, which are generally not regarded in Pd catalysis, is unprecedented. In situ
catalyst generation is favourable for ligands with less than tridentate chelation capacity and
presence of poorly chelating secondary NH-amine donor in the central position of the
polyamines hinders catalyst performance. However, the preformed tridentate complexes
yielded more attractive and living coupling catalyst efficiencies than their corresponding in
situ reactions especially when bulkier co-ligand such as pyridine occupies the fourth
-1
-1
coordination position (TOF of 5460 h for Pd(4-tol)py and 4800 h for Pd(4-ipr)py).
Therefore, mutual steric demands between the tridentate-chelated steric ligands such as 4-tol
and 4-ipr, and bulky co-ligand fragments cooperatively aids the generation of active species
from assembled precatalyst.
Keywords: Ligand effects, Suzuki-Miyaura C-C coupling, Homogeneous catalysis, Catalyst
development
Introduction
Biphenyl moieties are naturally occurring in numerous important molecular materials
and they are mostly synthesized through C-C coupling. Over the past few decades, many
transition metal complexes have been prepared and investigated for their roles as catalyst for
C-C coupling synthetic strategies [1–4]. However, the use of palladium species in cross
coupling of organic substrates stands out among all other capable metal catalysts [5–8].

Palladium-catalyzed carbon-carbon cross coupling has become a very powerful synthetic tool
for molecular scientists such as in natural products total synthesis, drug designs, industrial
production of fine chemicals and synthesis of next generation materials as well as bioactive
molecular materials [9–12].
Of all the palladium-catalyzed C-C procedures, Suzuki-Miyaura coupling is one of the
most frequently applied methods in routine organic syntheses. This is attributable to the wide
range of inexpensive and environmentally friendly organoboron compounds [13,14], mild
reaction conditions, high tolerance for functional group variation and ease of removal of the
boron byproducts relative to other organometallic reagents used in analogous coupling
reactions [15,16]. For decades, considerable efforts have continued to be dedicated to the
design and syntheses of palladium compounds in search of improved catalytic profiles. For
this purpose, various ligand designs ranging from monodentate to polydentate have been
studied [17–19].
Several highly active palladium precatalysts have already been commercialized
[
20,21] and are frequently supported by phosphine and N-heterocyclic carbene (NHC) ligands
while results for precatalysts bearing imine-based [22] ligands are also frequently being
reported (Scheme 1(i)) [23–26]. These successful phosphine and NHC complexes are often
˄
complemented by co-ligands of diverse donor types such as cyclometallating C N or allylic
organometallic chelates as well as halides [27]. However, such patented, mixed-ligand
precatalysts have ambitious synthetic architectures and high costs, but are also probably
confronted with air and moisture sensitivity [28] Consequently, exploring simpler and more
stable N-donor precatalysts can be considered necessary [29]. Notwithstanding, the simplicity
of the in situ ‘ligand + palladium salt’ approach in a catalytic reaction flask is also attractive
and a common practice for generating active species [30]. Precatalysts usually require
decomposition of some ligand donors for the purpose of creating vacant coordination sites

towards catalysis events,[31] but in situ catalyst generation approach may also assemble the
necessary components into the desired active configuration (Scheme 1 (ii)).
Steric rigidity of ligand backbone has become recognizes as a key factor against which
the success or otherwise of palladium catalysts are often discussed [32,33]. Consequently,
myriads of studied ligands backbones contain aromatic or fused aromatic rings as well as
other bulky fragments like t-butyl groups (Scheme 1(i)). However, could flexible aliphatic
ligand models incorporating bulky molecular moieties at certain positions also afford high
efficiencies? We considered that design and study of simple, flexible, aliphatic amine
chelates, which bear systematically varied substituent bulks at certain flanking or terminal
positions, would provide another dimension to the understanding of how ligand steric
characteristics affect efficiencies of resultant palladium active centers. Herein, we present
results for study of series of structurally and electronically diverse amine ligands and the
behaviour of their palladium species towards C–C cross coupling reactions. The series consist
of varying anionic bidentate, tridentate or tetradentate N- and O-donors (Scheme 2). Synthesis
and catalytic behaviour of some corresponding palladium complexes precatalysts were also
pursued for comparison.

Scheme 1: (i) Few examples of highly active and commercially available pre-catalysts [20–
2] and (ii) processes of active catalyst generation from precatalysts or in situ assembling
2
Scheme 2: Synthetic scheme and structures for the chelating amine ligands subjected to in situ
as well as palladium precatalyst studies.

Materials and methods
General information
All starting materials for synthesis as well as substrates for the catalytic experiments
were obtained commercially as reagent and used as supplied without further purification.
Microwave assisted procedures were conducted using Biotage Initiator 2.5 Microwave
Reactor for ligand preparations. All organic compounds were either purified by column
chromatography on silica gel or recrystallized. IR spectra were measured with a Bruker
Equinox FT-IR spectrometer equipped with a diamond ATR unit. Elemental analyses were
carried out on Leco CHNS-932 and El Vario III elemental analyzers. Mass spectrometry (MS)
1
13
analyses was conducted on a Bruker MAT SSQ 710 spectrometer. H and C NMR spectra
were collected on a Bruker AVANCE 400 MHz spectrometer using deuterated solvents.
Preparation of the ligands
General procedure: To a solution of the ethylenediamine derivative stirring in pyridine
in a 30 mL reactor vial set in ice bath was added the appropriate molar equivalent of the
sulfonyl chloride reagent in a dropwise manner. The reaction mixture was stirred for further
2
0 min at the ice bath temperature. Thereafter, the reactor vial was sealed and transferred to
o
the microwave reactor in which the reaction mixture was reacted at 120 C for 4 minutes.
Pyridine was removed under reduced pressure while the crude product was purified on a silica
gel column using carefully selected solvent ratio and sequence to elute the target ligand.
Chromatography on silica gel was typically carried out using 7:3 n-hexane / ethyl acetate
unless otherwise stated. The particular details and analytical characterization data for the
ligands are presented below:

N-(2-chloroethyl)-N-(2-(methylsulfonamido)ethyl)methanesulfonamide (1-Me): N-(2-
hydroxyethyl)ethylenediamine (1.80 g, 17.5 mmol), pyridine (15 mL), methanesulfonyl
chloride (6.00 g, 52.4 mmol), column chromatography firstly by n-hexane/ethylacetate (7:3)
on silica gel and then methanol (neat). 1-Me was obtained as a yellow crystalline solid. Yield
o
-1
(
1.10 g, 19%). M.p = 130 – 131 C. Selected IR data (ATR, cm ): v 3294w (N–H), 3246s,
1
2
931w (C–H alkyl), 1461vs, 1139vs, 972s, 755s. H NMR (400 MHz, d6-DMSO): δppm 7.14
(
t, J = 6.0 Hz, 1H), 3.73 (t, J = 7.0 Hz, 2H), 3.48 (t, J = 7.0 Hz, 2H), 3.28 (d, J = 6.8 Hz, 2H),
1
3
3
5
.12 (q, J = 6.6 Hz, 2H), 3.00 (s, 3H), 2.92 (s, 3H). C NMR: (101 MHz, d6-DMSO): 54.93,
4.76, 53.51, 47.37, 46.96, 43.02. MS (ESI) m/z 301.1 (100%). Anal. calc. for
1
C
6
H15ClN
2
O
5
S
2
. /
4
2
H O: C, 25.44; H, 5.52; N, 9.89; S, 22.64 %. Found: C, 25.69; H, 5.33; N,
9
.88; S, 22.49 %.
N-(2-chloroethyl)-4-methyl-N-(2-((4-
methylphenyl)sulfonamido)ethyl)benzenesulfonamide
(1-tol):
N-(2-
hydroxyethyl)ethylenediamine (0.54 g, 5.2 mmol), p-toluenesulfonyl chloride (3.0 g, 15.7
mmol), pyridine (15 mL). The compound was recrystallized in ethanol. Yield (0.97 g, 33 %).
o
-1
M.p = 110 – 111 C. Selected IR data (ATR, cm ): v 3296m (N–H), 2928w (C–H alkyl),
1
1
598m (C=C aromatic), 1435m, 1348vs, 1168vs, 1092vs, 760s. H NMR (400 MHz, CDCl
3
):
δ
ppm 7.76 (d, J = 8.3 Hz, 2H), 7.66 (d, J = 8.3 Hz, 2H), 7.37 – 7.24 (m, 4H), 5.21 (s, 1H), 3.54
(
t, J = 6.8 Hz, 2H), 3.34 (t, J = 6.8 Hz, 2H), 3.23 (dd, J = 9.3, 3.5 Hz, 2H), 3.18 (t, J = 5.1 Hz,
1
3
2
1
2
H), 2.44 (s, J = 2.3 Hz, 6H). C NMR (101 MHz, CDCl
3
): δ 144.25, 143.72, 136.56, 135.03,
+
29.93, 127.24, 51.69, 49.86, 42.49, 42.04, 21.55. MS (EI) m/z 431 (M , 12%): 381, 275,
1
46, 239, 184, 155, 91. Anal. calc. for C18
H23ClN
2
O
4
S
2
. /
4
EtOH: C, 50.22; H, 5.58; N, 6.33;
S, 14.49 %. Found: C, 50.54; H, 5.44; N, 6.40; S, 14.74 %.

2
-((2,4,6-triisopropyl-N-(2-((2,4,6-
triisopropylphenyl)sulfonamido)ethyl)phenyl)sulfonamido)ethyl
triisopropylbenzenesulfonate (2-ipr) and
triisopropylphenyl)sulfonamido)ethyl)amino)ethyl
2-iprNH): Triisopropylbenzenesulphonyl chloride (3.0 g, 9.9 mmol), N-(2-
2,4,6-
2-((2-((2,4,6-
2,4,6-triisopropylbenzenesulfonate
(
hydroxyethyl)ethylenediamine (0.34 g, 3.3 mmol) and pyridine (15 mL), column
o
chromatography by chloroform. (i) 1-ipr: Yield (0.15 g, 5%). M.p = 159 – 160 C Selected IR
-1
data (ATR, cm ): v 3323w (N–H), 2957s (C–H alkyl), 2869w (C–H alkyl), 1601s (C=C
1
aromatic), 1459s, 1329s, 1145vs, 1030vs, 780vs. H NMR (300 MHz, CDCl
3
): δppm 7.19 –
7
1
1
.10 (m, 5H), 4.18 – 3.84 (m, 8H), 3.62 – 3.32 (m, 4H), 3.24 – 3.05 (m, 2H), 2.89 (dt, J =
13
3.8, 6.9 Hz, 2H), 1.49 (s, 1H), 1.36 – 1.05 (m, 54H). C NMR (101 MHz, CDCl ): δ 154.03,
3
51.58, 150.89, 150.26, 124.24, 123.85, 66.77, 34.25, 34.20, 29.89, 24.90, 24.70, 23.53. MS
+
(
EI) m/z 635 (M - Ti-PBS, 10 %): 606, 340, 296, 267. Anal. calc. for C49
H
78
N
2
O
7
3
S : C,
6
5.15; H, 8.70; N, 3.10; S, 10.65 %. Found: C, 65.42; H, 8.84; N, 3.08; S, 10.16 %. (ii) 1-
o
-1
iprNH: Yield (1.08 g, 36 %). M.p = 178 – 179 C Selected IR data (ATR, cm ): v 3432w (N–
H), 2958s (C–H alkyl), 2869m, 1602s (C=C aromatic), 1564s, 1459s, 1310s, 1256s, 1144vs,
1
9
4
3
42vs. H NMR (300 MHz, d6-DMSO): δ 7.60 (t, J = 5.9 Hz, 1H), 7.19 (d, J = 3.0 Hz, 4H),
.80 (t, J = 5.1 Hz, 1H), 4.11 – 3.99 (m, 2H), 3.97 – 3.83 (m, 2H), 3.39 (q, J = 6.3 Hz, 2H),
.26 – 3.17 (m, 2H), 3.12 (t, J = 6.4 Hz, 2H), 2.96 – 2.84 (m, 4H), 1.15 (ddd, J = 17.3, 8.7, 5.0
Hz, 36H). 13C NMR (101 MHz, d6-DMSO): δ 153.37, 152.51, 151.08, 150.05, 133.29,
+
1
3
31.58, 124.30, 59.21, 48.80, 46.40, 33.78, 25.15, 24.88, 23.83. MS (EI) m/z 637 (M , 10%):
40 296, 267. Anal. calc. for C34
H
56
N
2
O
5
S
2
.½H O: C, 63.66; H, 8.88; N, 4.37; S, 10.00 %.
2
Found: C, 63.69; H, 8.80; N, 4.33; S, 9.70 %.
N,N-bis(2-(methylsulfonamido)ethyl)methanesulfonamide
(3-Me):
Diethylenetriamine (1.8 g, 17.5 mmol), methanesulfonyl chloride (6.0 g, 52.4 mmol,),

o
-1
pyridine (15 mL). Yield (1.02 g, 17 %). M.p = 117 – 118 C. Selected IR data (ATR, cm ): v
3
7
4
4
292m (N–H), 3021w (C–H aromatic), 2935w (C–H alkyl), 1306vs, 1139vs, 1074m, 1003vs,
1
67vs. H NMR (400 MHz, d6-DMSO): δppm 7.17 (d, J = 5.3 Hz, 2H), 3.25 (t, J = 6.6 Hz,
1
3
H), 3.19 – 3.06 (m, 4H), 2.98 (s, 3H), 2.92 (s, 6H). C NMR (101 MHz, d6-DMSO): δ
+
8.64, 41.97, 38.15. MS (EI) m/z 338 (M , 24%): 229, 151, 122, 108, 79, 42 Anal. calc. for
3
C
7
H
19
N
3
O
6
S
3
. /
4
2
H O: C, 23.96; H, 5.89; N, 11.97; S, 27.41 %. Found: C, 23.76; H, 5.36; N,
1
1.85; S, 27.48 %.
4
-methyl-N,N-bis(2-(4-methylphenylsulfonamido)ethyl)benzenesulfonamide (3-
tol): Diethylenetriammine (0.54 g, 5.2 mmol, p-toluenesulfonyl chloride (3.0 g, 15.7 mmol),
pyridine (15 mL). Recrystallization in ethanol affords 3-tol. Yield (2.04 g, 69 %). M.p = 220 -
o
-1
2
21 C. Selected IR data (ATR, cm ): v 3284s (N–H), 2913w (C–H alkyl), 1599s (C=C
1
aromatic), 1495s, 1322vs, 1156vs, 940s, 812vs. H NMR (400 MHz, CDCl
3
): δppm 7.78 (d, J =
8
4
1
1
.2 Hz, 4H), 7.63 (d, J = 8.2 Hz, 2H), 7.41 – 7.29 (m, 6H), 5.16 (s, 2H), 3.20 (d, J = 4.9 Hz,
1
3
H), 3.18 – 3.09 (m, 4H), 2.45 (s, 9H). C NMR: (101 MHz, CDCl3): δ 143.64, 136.67,
+
34.73, 129.92, 127.24, 50.52, 42.64, 21.53. MS (EI) m/z 566 (M , 25%): 381, 227, 209, 155,
39, 91. Anal. calc. for C25
H
31
N
3
O
6
3
S : C, 53.08; H, 5.52; N, 7.43; O, 16.97; S, 17.00 %.
Found: C, 53.06; H, 5.56; N, 7.54; S, 16.91 %.
2
,4,6-triisopropyl-N,N-bis(2-(2,4,6-
triisopropylphenylsulfonamido)ethyl)benzenesulfonamide,
azanediylbis(ethane-2,1-diyl))bis(2,4,6-triisopropylbenzenesulfonamide)
(3-ipr)
and
N,N'-
(
(3-iprNH):
Triisopropylbenzenesulphonyl chloride (1.98 g, 6.5 mmol), diethylenetriamine (0.24 g, 2.2
o
mmol), pyridine (15 mL). (i) 3-ipr: Yield (0.57 g, 29 %). M.p = 182-183 C. Selected IR data
-1
(
ATR, cm ): v 3294s (N–H), 2958s (C–H alkyl), 2868m, 1602s (C=C aromatic), 1564s,
1
1
317vs, 1149vs, 880s. H NMR (400 MHz, d6-DMSO): δppm 7.60 (t, J = 5.7 Hz, 2H), 7.18 (d,

J = 7.6 Hz, 6H), 4.03 (dt, J = 13.5, 6.7 Hz, 2H), 3.87 – 3.75 (m, 2H), 3.45 (d, J = 4.3 Hz, 2H),
.17 (t, J = 8.0 Hz, 4H), 2.89 (ddd, J = 10.2, 8.6, 4.3 Hz, 6H), 1.21 (d, J = 6.9 Hz, 12H), 1.18
3
1
3
(
d, J = 6.9 Hz, 12H), 1.11 (d, J = 6.7 Hz, 24H), 1.02 (d, J = 6.7 Hz, 12H). C NMR (101
MHz, d6-DMSO): δ 152.54, 151.05, 150.01, 133.16, 130.94, 123.98, 46.29, 33.79, 31.15,
+
2
9.14, 24.95. MS (ESI) m/z 924.4 ([M + Na] , 100 %). Anal. calc. for C49
H
79
N
3
O
6
S
3
.½H O
2
C, 64.58; H, 8.85; N, 4.61; S, 10.55 %. Found: C, 64.55; H, 8.99; N, 4.64; S, 10.45 %. (ii) 3-
o
-1
iprNH: Yield (0.92 g, 47 %). M.p = 326 – 327 C. Selected IR data (ATR, cm ): v 3295w,
1
2
7
959s, 2868w, 1602s, 1565w, 1363vs, 1119vs,1073m, 880m. H NMR (400 MHz, CDCl
3
) δ
.13 (s, 2H), 7.04 (s, 2H), 6.83 (s, 1H), 4.33 (dt, J = 13.4, 6.7 Hz, 2H), 4.04 (dt, J = 13.4, 6.7
Hz, 2H), 3.44 (d, J = 4.8 Hz, 2H), 3.39 (s, 2H), 2.87 (tt, J = 13.8, 6.9 Hz, 2H), 1.32 – 1.22 (m,
1
3
1
1
6
4
6H), 1.16 (d, J = 6.9 Hz, 24H). C NMR (101 MHz, d6-DMSO): δ 153.02, 150.11, 147.42,
42.41, 124.03, 121.79, 33.75, 31.15, 29.25, 28.47, 25.30. MS (ESI) m/z 658.3 ([M + Na]+,
+
0 %): 636.4 (M , 100 %). Anal. calc. for C34
H
57
N
3
O
4
2
S .(tol).EtOH: C, 62.19; H, 8.80; N,
.27; S, 9.77 %. Found: C, 61.79; H, 8.80; N, 4.26; S, 9.77 %.
N,N',N''-(nitrilotris(ethane-2,1-diyl))tris(4-methylbenzenesulfonamide)
(4-tol):
Tris-(2-aminoethyl)amine (1.0 g, 6.7 mmol), p-toluenesulfonyl chloride (5.09 g, 26.7 mmol).
Column chromatography on silica gel by n-Hexane/THF (1:1). Yield (1.05 g, 26 %). M.p =
o
-1
1
1
7
=
26 – 127 C. Selected IR data (ATR, cm ): v 3229w (N–H), 2959s (C–H alkyl), 2870m,
1
601s (C=C aromatic), 1564m, 1318s, 1151vs, 942vs. H NMR (400 MHz, d6-DMSO): δppm
.67 (d, J = 7.7 Hz, 6H), 7.36 (d, J = 7.4 Hz, 9H), 2.72 – 2.60 (m, 6H), 2.38 (s, 9H), 2.23 (t, J
13
6.0 Hz, 6H). C NMR (101 MHz, d6-DMSO): δ 143.09, 138.18, 130.16, 126.92, 53.54,
+
2
1.43. MS (EI) m/z 609 (M , 12 %): 424, 172, 155, 107, 91. Anal. calc. for
C
27
H
36
N
4
6
O S
3
.H
2
O: C, 51.74; H, 6.11; N, 8.94; S, 15.35 %. Found: C, 51.94; H, 6.16; N,
8
.98; S, 15.42 %.

N,N',N''-(nitrilotris(ethane-2,1-diyl))tris(2,4,6-triisopropylbenzenesulfonamide)
(
4-ipr): Tris-(2-aminoethyl)amine (0.37 g, 2.5 mmol), 2,4,6-tri-isopropylbenzenesulfonyl
Chloride ((3.03 g, 10.0 mmol). Recrystallization ethanol / THF. Yield (1.68 g, 71 %). M.p =
o
-1
2
1
7
46 – 247 C. Selected IR data (ATR, cm ): v 3326w (N–H), 2958s (C–H alkyl), 2870m,
1
602s (C=C aromatic), 1564m, 1363s, 1105vs, 941vs. H NMR (400 MHz,d6-DMSO): δppm
.69 (s, 2H), 7.24 (s, 6H), 6.95 (s, 2H), 4.58 (dt, J = 13.6, 6.8 Hz, 2H), 4.05 (dt, J = 13.1, 6.5
Hz, 6H), 3.49 (s, 12H), 2.93 (dd, J = 13.7, 6.8 Hz, 4H), 2.81 (dd, J = 13.7, 6.8 Hz, 1H), 1.19
1
3
(
dd, J = 14.0, 6.6 Hz, 60H), 1.10 (d, J = 6.8 Hz, 12H) ppm; C NMR (101 MHz,d6- DMSO):
δ 150.20, 147.60, 147.24, 142.41, 124.15, 121.78, 33.76, 29.34, 28.47, 25.23, 24.31, 23.86.
+
MS (ESI) m/z 1268.7 ([M + Na] ,12%): 945.6, 967.5. Anal. calc. for C66
H107ClN
4
O
8
4
S : C,
6
3.50; H, 8.64; N, 4.49; S, 10.27 %. Found: C, 63.47; H, 8.85; N, 4.46; S, 10.00 %
Syntheses of palladium complexes
General procedure: A mixture of ligand and one equivalent of Pd(OAc) were weighed
2
into a vial and 2 mL of acetonitrile added at room temperature. The solution was allowed to
stand for 3 days after which the microcrystalline product which came out was filtered and air-
dried. The analytical data and some reaction peculiarities for the obtained complexes are
presented below:
Pd(4-tol)H
obtained complex was dissolved in CHCl
of Pd(4-tol)H
2
O: 4-tol (30 mg, 0.05 mmol), Pd(OAc) (10 mg, 0.05 mmol). The
2
3
and layered with n-hexane, which lead to growing
o
2
O as yellow crystals. Yield (30 mg, 83 %), Mp = 198 – 199 C. Selected IR
-1
data (ATR cm ): v 3259br,m (N–H), 2957m (C–H alkyl), 1599s (C=C aromatic), 1425s,
+
+
1
333vs, 1133vs, 959vs. MS (ESI) m/z 753.1 ([M+Na] , 50 %): 735.2 ([M+Na-H O,] , 60 %),
2

+
6
31.2 ([L+Na] , 100 %). Anal. calc. for C27
H
36
N O
4 7
PdS : C, 44.35; H, 4.96; N, 7.66; S, 13.16
3
%
. Found: C, 44.49; H, 4.89; N, 7.64; S, 13.19 %.
Pd(4-tol)Py: 4-tol (30 mg, 0.05 mmol), Pd(OAc)
2
(10 mg, 0.05 mmol) in the presence
o
-1
of drops of pyridine. Yield (30 mg, 79 %), Mp = 203 - 204 C. Selected IR data (ATR cm ): v
3
1
1
4
434w (N–H), 3228m, 3071w (C–H aromatic), 2957m (C–H alkyl), 1597s (C=C aromatic),
+
+
449s, 1325vs, 1130vs, 973vs. MS (ESI) m/z 816.1 ([M+Na] , 100%): 735.2 ([M+Na-Py,] ,
5%). Anal. calc. for C32 PdS C, 48.51; H, 4.96; N, 8.84; S, 12.14%. Found: C,
8.50; H, 4.95; N, 8.90; S, 11.96%.
H
39
N
5
O
6
3
Pd(4-tol)i-PrOH: 4-tol (30 mg, 0.05 mmol) and Pd(OAc)
2
(10 mg, 0.05 mmol) in
o
THF (0.5 mL) and isopropanol (i-PrOH) (0.2 mL). Yield (30 mg, 80 %), Mp = 182 - 183 C.
-1
Selected IR data (ATR cm ): v 3256w (N–H), 2923w (C–H alkyl), 1599m (C=C aromatic),
+
1
3
448m, 1264m, 1133vs, 964vs, 812vs. ESI m/z 794.05 ([M+Na] , 10%): 754.10, 609.18,
01.07, 279.09. MS (EI) m/z: 514, 424, 294, 214, 199, 182, 155, 129, 91. Anal. calc. for
C
30
H
42
N
4
7
O PdS
3
.(THF) C, 48.30; H, 5.96; N, 6.63; S, 11.38%. Found: C, 48.14; H, 5.90; N,
6
.62; S, 11.13%.
Pd(4-ipr)H
2
O: 4-ipr (30 mg, 0.02 mmol) and Pd(OAc) (5 mg, 0.02 mmol). Yield (20
2
o
-1
mg, 78 %), Mp = 227 - 228 C. Selected IR data (ATR cm ): v 3259w (N–H), 2958m (C–H
alkyl), 2866m, 1600s (C=C aromatic), 1383s, 1270vs, 1133vs, 960vs. MS (ESI) m/z 1067
+
+
(
M 10%), 1089 ([M+Na] , 100 %). Anal. calc. for C51
H
84
N
4
O
7
PdS : C, 57.36; H, 7.93; N,
3
5
.25; S, 9.01%. Found: C, 57.11; H, 7.74; N, 5.25; S, 8.70%.

Pd(4-ipr)Py: 4-ipr (30 g, 0.02 mmol), Pd(OAc)
2
(5 mg, 0.02 mmol) and pyridine (0.5 ml).
Recrystallization in acetonitrile was carried out to obtain single crystals suitable for X-ray
o
-1
measurement. Yield (10 mg, 57 %), Mp = 160 - 161 C. Selected IR data (ATR cm ): v 2957s
(
C–H alkyl), 2869m, 1601s (C=C aromatic), 1562m, 1454s, 1244vs, 1119vs, 924vs, 825vs.
MS (ESI) m/z 1129 (M+ 47%), 1152 ([M+Na]+, 100%). Anal. calc. for
C
56
H
87
N
5
6
O PdS
3
.CH
3
CN.H O: C, 58.64; H, 7.81; N, 7.07; S, 8.10%. Found: C, 58.39; H,
2
7
.72; N, 7.08; S, 7.70 %.
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 [34–37]. The structures were solved by direct methods (SHELXS) and
refined by full-matrix least squares techniques against F 2
(SHELXL-97).
o
The hydrogen atoms of 1-Me as well as the hydrogen atoms bonded to the water
molecule O7 and the imines-group N4 of Pd(4-tol)H O and Pd(4-ipr)py were located by
2
difference Fourier synthesis and refined isotropically. All other hydrogen atoms were included at
calculated positions with fixed thermal parameters. All non-hydrogen, non-disordered atoms
were refined anisotropically [37]. Crystallographic data as well as structure solution and
refinement details are summarized in Table 1. The program XP [38]. was used for structure
representations.
Suzuki-Miyaura coupling catalysis experiment

In a typical reaction, (4-bromophenyl)methanol (B, 0.19 g, 1.0 mmol), (4-
acetylphenyl)boronic acid (A, 0.23 g, 1.4 mmol), potassium phosphate (0.26 g, 1.2 mmol),
palladium acetate (0.2 mol % relative to B) and a given ligand, (0.7 mol % relative to B) were
added together in a 10 mL round-bottom flask equipped with magnetic stirrer bar. Ethanol (3
o
mL) and water (1 mL) were added and the mixture was refluxed in an oil bath set at 100 C
for the desired reaction time. In the case of preformed palladium(II) complex, 0.2 mol % with
respect to (4-bromophenyl)methanol was used. An aliquot of the reaction mixture was taken
into a 10 mL conical flask and dried under vacuum to exclude the solvents. The residue was
1
then collected in deuterated DMSO and subjected to H NMR measurement. The reactivity of
the catalyst was evaluated by comparison of the NMR signals for the methylene (–CH –)
2
protons of (4-bromophenyl)methanol (B) at δ ≈ 4.4 ppm with that of the corresponding
biphenyl product at δ ≈ 4.7 ppm. The yields are estimated by determining the integral of the
product peak as a percentage of the sum of all observed methylene signals [30].
Results and discussion
Synthesis and characterization of the ligands
The series of the ligands 1-Me – 4-ipr were obtained by microwave-assisted
condensation of their respective amines and the corresponding sulfonyl chlorides using
pyridine as the base as well as solvent and the products were isolated in moderate yields.
During products isolation by column chromatography, some of the products required further
recrystallization. This is responsible for the lower yields recorded for some the ligands.
However, ligand 4-ipr was purified only by recrystallization from ethanol / THF solvent
mixture. Elemental analysis and spectroscopic data of the synthesized ligands reveal a notable
adduct-forming tendency of these amine ligands with solvents, water or even with a starting
material molecule. For example, ligands 3-iprNH and 4-ipr were isolated as adducts of their

corresponding sulfonyl chloride starting materials. Efforts to obtain the methylsulfonyl-
analogue of the tetradentate ligands 4-tol and 4-ipr (Scheme 2 (iii) and (iv)) were not
successful.
A notable finding during syntheses of the studied ligand is an unusual chlorination
reaction in which the sulfonyl chloride reagent served as the chlorinating agent and the
hydroxyl groups of primary aliphatic alcohols became replaced by chloride. This unexpected
substitution of the hydroxyl function of 2-((2-aminoethyl)amino)ethan-1-ol yielded the
chloro-substituted ligands 1-Me and 1-tol (Scheme 2 (ii)). Literature survey shows that
hydroxyl groups on an aliphatic alcohol can be substituted by chloride,[39,40] but this
reaction is normally carried out using chlorinating agents such as SOCl
2
, PCl
5
or triphosgene
in the presence of NEt or pyridine as base. The chlorination finding, which is hitherto not
3
reported, demonstrates that sulfonyl chloride reagents in pyridine can effectively achieves
chloro-substitution of primary aliphatic alcohols. Perhaps this may mark a new aspect of
sulfonyl chloride utility as well as a novel pathway to the synthesis of chlorinated compounds.
Within the context of our study, a mechanistic thought for this reaction is presented in
Scheme 3.
While methanesulfonyl chloride and p-toluenesulfonyl chloride reacted with 2-((2-
aminoethyl)amino)ethan-1-ol to give only the chloro-substituted analogues 1-Me and 1-tol
respectively, expected sulfonate ester products were obtained when 2,4,6-
triisopropylbenzenesulfonyl chloride was deployed, which lead to ligands 2-ipr and 2-iprNH
(
Scheme 1). The crystal structure of 1-Me is presented in Fig. 1. This difference in reaction
outcomes from different sulfonyl chloride reagents is also considered to be an indication that
the electronic and steric properties in the obtained ligands towards the catalytic study should
also vary.

Scheme 3: Proposed mechanism for the reaction.
Synthesis and characterization of the palladium complexes
All the palladium(II) complexes were generally obtained in good yields by stirring
Pd(OAc)
Scheme 4). Despite several efforts to obtain palladium(II) complexes for all prepared ligands
and with varying reaction conditions, defined complexation products only resulted for ligands
-tol and 4-ipr. This observation is attributable to the higher chelation character as well as
2
and a given member of the ligand series in suitable solvent at room temperature
(
4
steric bulk of the tolyl- and 1,3,5-triisopropylphenyl-substituent of the 4-tol and 4-ipr ligands
respectively, which are capable of preventing other coordination alternatives such as bis-
ligand situations. X-ray single crystal data were collected for the palladium complexes Pd(4-
tol)H O and Pd(4-ipr)py (Figs. 2 and 3). It is noteworthy that various neutral monodentate
2
donor species such as water, iso-propanol and pyridine could be placed in the fourth
coordinate position around the palladium coordination square plane. Elemental analyses and
spectroscopic data gave good agreement with the identity of the palladium complexes.

Scheme 4: Synthetic route and compositions of the obtained palladium complexes of ligands
-tol and 4-ipr
4
X-ray structures
Data for their structural refinement and processing parameters are collected in Table 1
and their ortep plots are presented in Figs. 1 – 3. Structure of ligand 1-Me confirms the
chloro-substitution of the hydroxyl group and is assembled with extensive intermolecular
hydrogen-bonding interactions (Fig. 1). Crystal structures of complexes Pd(4-tol)H O and
2
Pd(4-ipr)py revealed tridentate ligand chelation even though the ligands 4-tol and 4-ipr
possess tetradentate chelation capability (Figs. 1 and 2). The limitation to tridentate chelation
is necessitated by the square planar coordination geometry of the palladium(II) metal center.
Bond lengths around the coordination center for the structures of Pd(4-tol)H O and
2
Pd(4-ipr)py are within expected values [41]. Both palladium centers are in slightly distorted
square planes and all the Pd–N bond length are within a range of 2.00 – 2.07 Å. A shorter
bond length is observed between the palladium metal center and the central nitrogen donors of
ligands 4-tol (Pd1–N1 in Pd(4-tol)H
2
O) and 4-ipr (Pd1–N2 in Pd(4-ipr)py) than for the
remaining Pd–N bonds. This suggests that the central nitrogen donors of the 4-tol and 4-ipr

ligands possess stronger donor strengths than the sulfonyl-substituted nitrogen donors and is
attributable to the electron-releasing nature of the alkyl fragments around the central nitrogen
as opposed to the electron-withdrawing influence of the sulfonyl-substituents on the
remaining N-donors. The participation of the sulfonyl oxygen atoms in inter- and
intramolecular hydrogen bonding as illustrated by the co-crystallized water in Pd(4-tol)H O
2
is worthy of note (Figs. 1 and 3). Such functions in the proximity of active metal center may
play important roles in ordering oxidative insertion steps during the catalytic process.
It is also notable that significantly larger degree of flexibility exists in the chelation
environment of Pd(4-tol)H
the two tolyl aromatic rings of the coordinating secondary amines arms on ligand 4-tol as
observed in complex Pd(4-tol)H O were flexible enough to tolerate folding and being placed
2
O relative to that of Pd(4-ipr)py. In particular, the disposition of
2
in close proximity to each other (separation between centroids of these tolyl rings is 5.59 Å,
Fig. 2). On the other hand, the triisopropylphenyl rings on the chelated secondary amine arms
of ligand 4-ipr as observed in Pd(4-ipr)py exhibited lesser steric tolerance such that these
rings stand pushed away from the coordination center with 11.80 Å distance between their
centroids (Fig. 3).

Figure 1: Molecular structure of 1-Me and its intermolecular hydrogen-bonding
characteristics viewed along two perpendicular paths
Figure 2: Ortep plot of complex Pd(4-tol)H
solvents have been omitted for clarity (Selected bond lengths: Pd1−N1 = 2.000(3), Pd1–N2 =
.047(3), Pd1−N3 = 2.034(3), Pd1−O7 = 2.045(3)).
2
O drawn at 50 % probability level. Protons and
2
Figure 3: Ortep plot of complex Pd(4-ipr)py drawn at 50 % probability level. Some protons
and solvents have been omitted for clarity(Selected bond lengths: Pd1−N1 = 2.065(2), Pd1–
N2 = 2.029(2), Pd1−N3 = 2.057(2), Pd1− N5 = 2.040(2)).

Table 1: Crystal data and refinement details for the X-ray structure determinations of the
2
compounds 1-Me, Pd(4-tol)H O and Pd(4-ipr)py.
Compound
1-Me
Pd(4-tol)H
2
O
Pd(4-ipr)py
PdS
1187.96
-140(2)
monoclinic
C 2/c
38.5341(6)
11.3209(2)
33.2963(5)
90
124.138(1)
90
formula
fw (g∙mol )
6
C H
15ClN
2
O
4
S
2
C H
27 36
N O
4 7
PdS
3
C H
58 92
N O
6 7
3
-1
278.77
-140(2)
monoclinic
P 2 /c
731.18
-140(2)
triclinic
T(°C)
crystal system
space group
a/ Å
b/ Å
c/ Å
α/°
1
P ī
13.1407(7)
5.1069(2)
17.3127(9)
90
90.436(2)
90
13.1002(3)
13.7093(3)
18.0705(5)
73.425(2)
78.114(2)
86.179(1)
3043.71(13)
4
β/°
γ/°
V/Å3
Z
ρ (g∙cm )
1161.79(10)
4
12022.3(3)
8
-3
1.594
6.85
1.596
8.67
1.313
4.67
-1
µ (cm )
measured data
data with I > 2σ(I)
10589
2221
29498
10785
35330
11782
unique data (Rint
)
2652/0.0477
13771/0.0369
13731/0.0385
wR (all data, on
2
0
.1078
0.1022
0.0877
2
a)
F )
R
S
1
b)
(I > 2σ(I)) a)
0.0524
1.116
0.439/-0.523
multi-scan
0.0523
1.062
0.0403
1.058
Res. dens./e∙Å-
absorpt method
absorpt corr Tmin
CCDC No.
3
0.618/-0.695
multi-scan
0.6578/0.7456
1850774
0.529/-0.652
multi-scan
0.6935/0.7456
1850775
/
max
0.6765/0.7456
1850773
= (F
a)
2
2 2
2 2 1/2
-1
2
2)
Definition of the R indices: R
1
o
-F
c
)/F
o
2 2
; wR
2
= {[w(F
-N )} .
o
-F
c
) ]/[w(F
o
) ]} with w = σ (F
o
2
2
2
b)
2
1/2
+
(aP) +bP; P = [2F
c
+ Max(F
O
]/3; s = {[w(F
o
-F
c
) ]/(N
o
p
Determining suitable catalytic reaction parameters
The catalytic study started with search for an average reaction setting under which all
the ligand frameworks would then be comparatively studied. This setting is aimed to be the
constant set of reaction parameters that may allow observation of the influence of ligands’
molecular variations on their capabilities to generate active species either via in situ ‘ligand +
Pd(AcO)
as representative members of the ligand series to test for suitable reaction time,
Pd(OAc) :ligand ratio, boronic acid ratio and additive base in the coupling of (4-
2
’ route or from palladium complex precatalysts. Ligands 3-tol and 3-ipr were used
2

acetylphenyl)boronic acid (A) and (4-bromophenyl)methanol (B) as a typical Suzuki-Miyaura
coupling reaction. The suitability of catalytic substrates was decided because the methylene (–
1
CH
2
–) function on the (4-bromophenyl)methanol (B) substrate allows for the ease of H-NMR
tracking of the aryl bromide conversion to coupled product. This functional group was found
1
to be advantageous because there is no interference of H-NMR signals around the 4.46 ppm
region where the methylene group of B gives signal.[30] The results for reaction parameter
testing are summarized in Table 3.
o
Using 3:1 EtOH/H
2
O (4 mL), K
2
CO
3
(1 mmol), oil bath temperature of 100 C,
Pd(OAc)
2
(0.2 mol %) and ligand 3-ipr (0.4 mol %), coupling reactions of A and B were
monitored at 10, 30 and 60 minutes. The obtained yields of the A–B coupling product indicate
that there is no benefit for refluxing beyond 10 minutes (entries 1 – 3, Table 2). This result
suggests that the active species are either short-lived or that a substrate is rapidly converted
via side reactions to unwanted species.
Continuing with 10 min reflux duration and keeping constant other reaction
parameters above, increased amounts of ligand 3-ipr from 0.4 mol % to 0.7 and 1.0 mol %
was deployed against 0.2 mol % Pd(OAc)
the catalytic results (entries 1, 4 and 5, Table 2). Nonetheless, 0.7 mol % of ligand was
employed against 0.2 mol % Pd(OAc) for further reactions for the sole purpose of ensuring
that access of palladium to ligand in the low concentration catalyst system is not limited.
Investigating different base additives proved K PO to be the better base for the catalyst
systems under study (entries 4 and 6 – 9, Table 2) [42,43]. Since the coupling yield difference
between 1.2 and 1.4 equivalents of K PO is not dramatic (entries 10 and 11, Table 2), further
2
, which did not produce any significant effects on
2
3
4
3
4
reactions were carried out using the 1.2 mole equivalents of the base in order to allow for
observation of molecular effects in catalytic performances. Rather than utilize higher loadings
of the base, the lesser K
3
PO
4
loading would increase the chance of observing differences
caused by the ligand architectures. Consequently, the concluded catalytic reaction setting

entails 4mL of 3:1 EtOH/H
2
O, K
3
PO
4
(1.2 mmol), 0.7 mol % ligand + 0.2 mol % Pd(OAc) ,
2
o
1
.2 mmol A, 1 mmol B, oil bath temperature of 100 C and 5 minutes reflux duration. The
choice of 4mL of 3:1 EtOH/H O mixture as solvent is based on our previous studies [30].
2
Temperature readings were taken by inserting a thermometer into some refluxing reaction
o
mixtures, which showed values of about 81 C though the oil bath was thermostated at 100
oC.
Table 2: Testing of different reaction parametersa
Entry
Ligand (mol %)
3-ipr (0.4)
3-ipr (0.4)
3-ipr (0.4)
3-ipr (0.7)
3-ipr (1.0)
3-ipr (0.7)
3-ipr (0.7)
3-ipr (0.7)
3-ipr (0.7)
3-tol (0.7)
3-tol (0.7)
Time (min)
Base (mmol)
Yield (%)b
1
2
3
4
5
6
7
8
9
10
30
60
10
10
10
10
10
10
10
10
K
K
2
K
2
K
2
2
CO
CO
CO
CO
CO
3
3
3
3
3
(1.0)
(1.0)
(1.0)
(1.0)
(1.0)
18
19
19
20
19
17
39
17
25
65
78
K
2
Na
PO
N (1.0)
KOH (1.0)
2
CO
3
(1.0)
K
3
Et
4
(1.0)
3
1
1
0
1
K
3
K
3
PO
PO
4
(1.2)
(1.4)
4
a
o
Reaction conditions: Solvent: 3:1 EtOH/H
ligand amount (0.4 – 1.0 mol %), Pd(OAc)
bromophenyl)methanol (1 mmol). Yield was determined by H-NMR and reported to the nearest whole number.
2
O (4 mL), base (1.0 – 1.4 mmol), oil bath temperature set at 100 C,
(0.2 mol%); (4-acetylphenyl)boronic acid (1.2 mmol), (4-
2
b
1
Ligand character and palladium catalyst activity
The different series of ligands prepared in this experiment were subjected to the
catalytic studies under the same reaction conditions described above. The results of the in situ
catalysis are presented in Table 3 which generally shows that ligand has some influence on
the activity of the palladium active centers (entry 1 vs other entries). In particular, bulkiness
of the ligand systems correlated with catalyst activities. As illustrated in Table 3, in the
presence of ligands with the triiso-propylphenly-substituents, higher catalyst performances
were recorded relative to their corresponding analogues with the less bulky methyl- or tolyl-

substituents (e.g. entry 2 vs 4 shows 1-Me = 60 % while 2-ipr = 72 %; entry 6 vs 8 shows 3-
Me = 51 % while 3-ipr = 61 %; entry 10 vs 11 shows 4-tol = 16 % while 2-ipr = 60 %). The
-1
lower turnover frequency (TOF) values for the chloro-substituted ligands 1-Me (3600 h ) and
-1
-1
-1
1
-tol (3000 h ) relative to the bulkier analogues 2-ipr (4440 h ) and 1-iprNH (4020 h ) is
also in agreement with this observation. Therefore, despite the flexibility of alkyl fragments in
these amine-based ligands, the introduction of bulky units at the flanking ends of the chains
could be employed to aid construction of active palladium species. To the best of our
knowledge, this fact has not been so established elsewhere.
Furthermore, it is also noteworthy that chelation characteristics in the ligand series
influenced catalytic outcomes. Ligands with bidentate chelation potentials proved to be better
candidates above their counterparts possessing tridentate or tetradentate chelation capacities.
-1
In particular, highest TOF values resulted from the O^N^N ligands 2-ipr (4440 h ) and 2-
-1
iprNH (4020 h ) while the potentially tridentate N^N^N ligands yielded lower catalytic
performances. The donor behaviour of oxygen in the 1- and 2-series of ligands can be
considered non-favourable. Thus, these ligands would generally be bidentate. Even the 1-Me
and 1-tol that lack the supporting bulkiness showed reasonable catalyst efficiencies
comparable to the best outcomes from the tridentate or tetradentate ligand frameworks 3-Me –
4
-ipr (entries 2 and 3 vs entries 6 – 11). Despite the presence of steric bulk of tosyl-
substituents on 4-tol and considering that this ligand possesses a third, non-coordinated arm,
which should constitute additional steric demand when ligand 4-tol is involved in a tridentate
chelation environment, it is worthy of note that this ligand framework (4-tol) displayed one of
the lowest capacity to generate active catalyst species through the utilized reaction setting
-1
(
entry 10, TOF 960 h ). In fact, the ligand acted as poison when compared to Pd(OAc)
2
(entry
-1
1
, TOF 2340 h ) and it indicates that the tridentate chelation potential proved to be a stronger
determining factor for catalyst efficiency above the steric or electronic considerations.

An additional key observation in catalytic outcomes obtained in the presence of the
various ligands is that the ligand analogues having secondary amines situation at the middle
N-donor position displayed reduced catalytic efficiencies relative to their tertiary N-donor
analogues. This may be attributed to possible weaker chelating potentials of secondary amines
relative to tertiary more so that the presence of three electron-inducing alkyl-substituents in
the tertiary amines should also cause better donor and chelating tendencies. In other words,
the results suggest that reluctant donor character at the middle donor position of such
polydentate ligands as in the ligands 3- and 4-series is capable of frustrating eventual
chelation and should be avoided.
Table 3: Catalytic performance for the series of ligands via in situ active site generationa
-
1
Entry
Ligand
No ligand
1-Me
1-tol
2-ipr
2-iprNH
3-Me
3-tol
3-ipr
3-iprNH
4-tol
Yield (%)
TOF (h )
2340
3600
3000
4440
4020
3060
3240
3660
900
1
2
3
4
5
6
7
8
9
39
60
50
72
67
51
54
61
15
16
60
1
1
0
1
960
3600
4-ipr
a
Reaction conditions: 4mL of 3:1 EtOH/H
2
O, K
3
o
PO
4
(1.2 mmol), 0.7 mol % ligand + 0.2 mol % Pd(OAc) , 1.2
mmol A, 1 mmol B, oil bath temperature of 100 C and 5 minutes reflux duration. Yield was determined by H-
2
1
NMR and reported to the nearest whole number.
Catalytic performance of the palladium complexes
Table 4 shows the catalytic performance of the preformed palladium precatalysts
according to the established catalytic setting above. However, only 0.2 mol % of the
respective complexes were introduced as catalyst sources and some further results under
reaction times of 5 – 60 minutes were obtained. One key observation is that the precatalysts

generally displayed capability to generate living catalytically active species in the course of
reaction life unlike the very early termination of catalyst activities experienced for the
corresponding in situ method (Fig. 4, Table 4; catalytic activities generally increase as time
progresses). For the studied compounds, it is therefore obvious that to assemble ligands and
palladium(II) ions into useful catalyst configurations via the in situ complexation approach
suffers obvious limitations compared to applying preformed complexes (Scheme 1, bottom).
An important conclusion from catalytic data is that the size of the co-ligand correlates
with catalytic performance; order of yields for varying co-ligands (L) in Pd(4-tol)D followed
H
2
O < isopropanol < py while for Pd(4-ipr)D also followed H
2
O < py (Fig. 4, see also
O and Pd(4-tol)iPrOH
Supplementary Information, Table S1). While complexes Pd(4-tol)H
2
showed steady increase of yield with time, the remaining complexes could be observed to
rapidly couple the substrates. Therefore, it is also noteworthy that complexes Pd(4-tol)py and
Pd(4-ipr)py displayed the highest initial rates having converted as much as 80 % of the
substrate within the first 5 minutes of reaction life. Consequently, it could be suggested that
the presence of pyridyl moiety constituted further steric inconveniences to the already bulky
ligand-palladium assembly of complexes Pd(4-tol)py and Pd(4-ipr)py, which suggestively
implies lower coordination stabilities. Such steric demands probably created the ease of path
for dismantling of complexation bonds towards forming the active catalyst. Still focusing on
steric characteristics, the catalytic profile for complex Pd(4-ipr)H
2
O, which is well more
impressive above that of complex Pd(4-tol)H
2
O, is attributable to the bulkiness of the iso-
propyl-substituents (Fig. 4).

1
00
8
6
4
2
0
0
0
0
0
Pd(4-tol)H2O
Pd(4-tol)iPrOH
Pd(4-tol)py
Pd(4-ipr)H2O
Pd(4-ipr)py
0
10
20
30
40
50
60
Time (min)
Fig. 4: Catalytic performances of the prepared palladium complexes at varying times
Conclusion
Catalysis results obtained from comparatively studying the synthesized ligands under
the same reaction conditions and via the in situ ‘ligand + Pd(OAc) ’ catalyst generation
2
proved that very high catalyst performances can also be enabled by presence of simple,
aliphatic, diamine or triamine chelates when appropriate sterically bulky functions are
anchored to the chains. This result is considered important because general conclusions that
catalytic efficiency requires sterically bulky and rigid ligands exemplified by phos
architectures create impressions that flexible aliphatic-based ligand frameworks will not
support useful active site generation. Within 5 min reflux, 72 % yield was recorded in the
presence of ligand ‘2-ipr + 0.2 mol % Pd(II)’ loading. Furthermore, higher TOF values were
obtained in the presence of all triiso-propylphenly-substituented ligands relative to their
respective analogues possessing the less bulky methyl- or tolyl-substituents.
Additionally, it was concluded that attaining desirable catalyst efficiencies by these
polydentate, aliphatic amines is largely favoured for ligands with less than tridentate chelation

tendencies. Despite the presence of steric bulk of tosyl-substituents on the tridentate-chelating
-1
ligand 4-tol (TOF 960 h ), it actually aided poisoning of Pd(OAc) under in situ approach,
2
-1
which yielded TOF = 2340 h without ligand additions. It was also concluded that presence
of secondary amines N-donor in the central position of the ligands compromised chelation
potentials relative to their tertiary N-donor analogues, which resulted in poorer catalytic
worth.
Finally, complexes of ligands 4-tol and 4-ipr revealed that preformed complexes of
the studied ligand frameworks possess significantly better capability to generate efficient and
living active species than their corresponding in situ reactions. It was also observed that,
despite the tridentate chelation in the complexes Pd(4-tol)Py and Pd(4-ipr)py, they displayed
-1
-1
the highest efficiencies (5460 h and 4800 h respectively), which is attributed to the benefit
of incorporating a bulkier co-ligand moiety such as pyridine to aid weakening of chelation.
Appendix A. Supplementary data
CCDC 1850773 – 1850775 contains the supplementary crystallographic data for 1-Me, Pd(4-
2
tol)H O
and Pd(4-ipr)py. These data can be obtained free of charge
via http://www.ccdc.cam.ac.uk/conts/retrieving.html, or from the Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223-336-033; or e-mail:
deposit@ccdc.cam.ac.uk.
Acknowledgements

HOO is grateful to the Government of the Federal Republic of Nigeria for financial support
through TETfund research grants (TETfund AST&D year 2012 intervention) and to Adeyemi
College of Education, Ondo, Nigeria for granting study leave. AOE is thankful to Alexander
von Humboldt Foundation for granting post-doctoral fellowship. The financial support by the
Deutsche Forschungsgemeinschaft (DFG) is gratefully acknowledged (PL 155/11, PL 155/12
and PL155/13).
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