Synthesis of new triazolyl-oxazoline chiral ligands and study of their coordination to Pd(II) metal centers

Article abstract of DOI:10.1016/j.ica.2019.119129

We report an improved protocol for the synthesis of TryOx, a family of N,N chiral ligands in which a 1,2,3-triazol-4-yl moiety bears a chiral 2-oxazoline as the substituent in 4 position. TryOxs were successfully employed for the preparation of cationic P

Full text of DOI:10.1016/j.ica.2019.119129

Journal Pre-proofs
Synthesis of new triazolyl-oxazoline chiral ligands and study of their coordina-
tion to Pd(II) metal centers
Alberto Scrivanti, Roberto Sole, Marco Bortoluzzi, Valentina Beghetto, Noemi
Bardella, Alessandro Dolmella
PII:
S0020-1693(19)31100-4
https://doi.org/10.1016/j.ica.2019.119129
ICA 119129
DOI:
Reference:
Inorganica Chimica Acta
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Received Date:
Revised Date:
Accepted Date:
29 July 2019
3 September 2019
4 September 2019
Please cite this article as: A. Scrivanti, R. Sole, M. Bortoluzzi, V. Beghetto, N. Bardella, A. Dolmella, Synthesis of
new triazolyl-oxazoline chiral ligands and study of their coordination to Pd(II) metal centers, Inorganica Chimica
Acta (2019), doi: https://doi.org/10.1016/j.ica.2019.119129
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1
Synthesis of new triazolyl-oxazoline chiral ligands and study of their coordination to
Pd(II) metal centers
by
Alberto Scrivanti, a,b* Roberto Sole, a Marco Bortoluzzi, a,b Valentina Beghetto, a
Noemi Bardella, a Alessandro Dolmella c
a) Dipartimento di Scienze Molecolari e Nanosistemi, Università Ca’ Foscari Venezia, Via
Torino 155, 30172 Mestre - Italy
b) CIRCC, via C. Ulpiani 27, 70126 Bari - Italy
c) Dipartimento di Scienze del Farmaco, via Marzolo 5, 35131 Padova - Italy
Abstract
We report an improved protocol for the synthesis of TryOx, a family of N,N chiral ligands in
which a 1,2,3-triazol-4-yl moiety bears a chiral 2-oxazoline as the substituent in 4 position. TryOxs
were successfully employed for the preparation of cationic Pd(II)-allyl of formulation
[Pd(allyl)(TryOx)]+ in which they behave as bidentate N,N chelating ligands. On the other hand,
reaction of TryOxs with an equimolecular amount of [PdCl2(CH3CN)2] leads to the formation of
neutral complexes which according to NMR, ESI-MS and molar mass determination (VPO) appear
to be dimeric species of formulation [PdCl(µCl)(TryOx)]2 in which monodentate TryOxs link to
palladium with the N atom of the oxazoline ring. X-rays diffraction studies show that upon
crystallization these dimers transform into monomeric compounds of formulation [PdCl2(TryOx)]
where the ligands behave as N,N chelating.
Treatment of the [PdCl(µCl)(TryOx)]2 dimers with an equivalent of TryOx affords
mononuclear neutral dichloro species of formulation [PdCl2(TryOx)2]. X-ray diffraction studies
show that the two TryOx units are equivalent behaving as monodentate ligands coordinated to the
metal through the oxazoline N atom.
Keywords: oxazoline, triazole, bidentate ligands, palladium, palladium allyl complexes.
*Corresponding author, e-mail: alberto.scrivanti@unive.it

2
1. Introduction
Design and development of novel and efficient ligands is a core activity in transition-metal catalysis
because organic ligands properties ultimately affect the steric and electronic characteristics of metal
centers allowing to improve and tune activity, regioselectivity and (when appropriate)
enantioselectivity of the metal-catalyzed reactions. Expected benefits include milder reaction
conditions, improved chemo-, regio- and stereo-selectivity eventually leading to more sustainable
chemical processes.
After more than 40 years, pyridine-oxazolines (PyOx, Scheme 1), a class of chiral N,N-bidentate
ligands originally conceived by H. Brunner in 1980’s [1,2], continue to attract chemists interest as
confirmed by the recent reviews appeared in the literature [3-5].
Likewise, in the last two decades nitrogen ligands containing triazole rings drew increasing
attention not only in relation with their coordination characteristics but also because their structures
can be easily modified taking advantage of the modular nature of the copper catalyzed [2+3]
alkyne-azide cycloaddition [6,7].
Inspired by the chemical structure of PyOx ligands we devised the synthesis of a novel type of
chiral N,N-bidentate ligand in which a chiral oxazoline ring bears as the substituent a triazolyl
moiety (Scheme 1).
O
Chiral PyOx ligand
*
N
N
R
R1
O
N
N
4
Chiral triazolyl-oxazoline:
TryOx ligand
*
N
1
N
3
R
2
Scheme 1. Chemical structures of PyOx and of TryOx ligands
We are confident this novel class of ligands will find applications in different fields of coordination
chemistry and asymmetric catalysis. In this connection, it is to remark that owing to the modular
nature of triazole synthesis it will be possible to prepare libraries of these ligands allowing for a fine
tuning of their characteristics.
Furthermore, it should be noted that beyond the plain structural similarity with PyOx ligands,
TryOxs could display some unprecedented coordination chemistry. As a matter of fact, it is
generally assumed that while the σ-donor strengths of the triazole and pyridine are not very
different, pyridines are considered to be a better π acceptors than 1,2,3-triazoles. [8]. These

3
characteristics can be exploited in other fields; for instance in a preliminary account on the
synthesis of a TryOx prototype [9] we have already shown that TryOxs can be successfully
employed in combination with some lanthanides to give photoluminescent species.
We wish to report herein an improved protocol for the synthesis of chiral TryOx ligands and
preliminary studies on their coordination to Pd(II) metal centers. Inspection of the literature reveals
that achiral TryOx ligands (i.e. species as depicted in Scheme 1 in which R = H) have been
previously synthesized by Cook [10] and by Maas [11]. In particular, it is worth to mention that
Maas showed by X-ray diffraction analysis that the achiral TryOx having R1 = benzyl and R = H
behaves towards Cu(II) as a monodentate ligand, coordination occurring through the N atom of the
oxazoline.

4
2. Experimental
2.1 Materials and instrumentation
Commercial solvents (Aldrich) were purified as described in the literature [12].
(S)-(+)-2-Amino-1-butanol, (S)-(+)-2-amino-4-methyl-1-pentanol [L-leucinol, (S)-(+)-
leucinol], and (S)-(+)-2-amino-3,3-dimethylbutyric acid (L-tert-leucine) were purchased from
Aldrich. Benzylazide [13] and t-butylazide [14] were prepared according to procedures reported in
the literature (caution: aliphatic azides and HN3 are explosive and toxic). 1-Benzyl-1H-
[1,2,3]triazole-4-carboxylic acid was prepared according to the procedure described by Gautier
[15]. (S)-(+)-2-Amino-3,3-dimethylbutanol (L-tert-leucinol) was synthesized by reduction of (S)-
(+)-2-amino-3,3-dimethylbutyric acid according to a literature procedure [16]. 4-(4,6-dimethoxy-
1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) was prepared as described by
Kunishima [17]. [Pd(3-C3H5)Cl]2 was prepared according to the method described by Hartley [18].
All syntheses were carried out under inert atmosphere (nitrogen) using standard Schlenk techniques.
1H and 13C {1H} NMR spectra were recorded on a Bruker AVANCE 300 spectrometer operating at
300.21 and 75.44 MHz, respectively. The chemical shift values of the spectra are reported in δ units
with reference to the residual solvent signal. The proton assignments were performed by standard
chemical shift correlations as well as by 1H 2D COSY experiments.
ESI-MS analyses were performed using a Finnigan LCQ-Duo ion-trap instrument, operating in
positive ion mode (sheath gas N2, source voltage 4.0 KV, capillary voltage 21 V, capillary
temperature 200 °C). Sample solutions were prepared by dissolving Pd complexes (about 1 mg) in
methanol (1 mL) and then further diluting with methanol (1:30). All mass spectra were recorded on
freshly prepared solutions.
Elemental analyses (C, H, N) were carried out at the University of Padua using a Fison EA1108
microanalyzer.
IR spectra were collected in the range 4000 – 400 cm-1 using a Perkin-Elmer Spectrum One
spectrophotometer.
Melting points were determined using a Büchi B-535 apparatus.
Optical rotatory power values () were determined using a Jasco P-2000 polarimeter (Na lamp at 25
°C).
Molar masses in solution were measured by Vapor Phase Osmometry (VPO) employing chloroform
solutions (37 °C) on a Knaeur Dampfdruck Osmometer.
2.2 Ligands synthesis
(1-t-Butyl-1H-[1,2,3]triazol-4-yl) metanoic acid (1b)

5
In a mixture of t-BuOH (15 mL) and water (15 mL) were dissolved 1.50 g (15.00 mmol) of t-BuN3
and 1.40 g (1.5 ml, 16.6 mmol) of methyl propiolate. Then, under nitrogen, were added in the order
a solution of sodium ascorbate (0.29 g, 1.50 mmol) in water (2 mL) and finally a solution of
CuSO4∙5H2O in water (0.19 g, 0.75 mmol in 2 mL of H2O). The mixture was kept under stirring and
then after 24 hours it was taken to dryness. The brown solid residue was extracted with
dichloromethane, filtered and taken to small volume. The resulting oil was chromatographed on
silica gel (eluent: dicholoromethane/diethyl ether = 95/5) to give the methyl ester of 1b as a white
solid.
1H NMR (CDCl3, 298 K) : 8.16 (s, 1H), 3.94 (s, 3H), 1.70 (s, 9H).
The recovered ester was dissolved in MeOH (30 mL) and treated with 10 mL of an 10% aqueous
NaOH solution. The mixture was stirred for 3 h, then the methanol was distilled off at reduced
pressure. The aqueous phase was neutralized at pH = 7 by addition of 5% aq. HCl, and extracted
with dichloromethane (3  30 mL). The reunited organic phases were dried upon anhydrous
MgSO4, filtered and taken to dryness in high vacuum to give 1b as a white solid (1.86 g, 73%
yield).
1H NMR (acetone-d6, 298 K) : 8.53 (s, 1H), 3.77 (b s, 1H, COOH), 1.73 (s, 9H).
13C NMR (CDCl3, 298 K) : 164.1, 138.7, 125.7, 60.8, 30.0.
(S)-1-Benzyl-N-(1-hydroxy-butan-2-yl)-1H-1,2,3-triazol-4-carboxyamide (2a)
In a round bottomed flask, 0.48 mL (5.00 mmol) of (S)-(-)-2-amino-1-butanol and 1.03 g of 1a
(5.00 mmol) were dissolved in 50 mL of acetonitrile. Then 3.00 g (5.40 mmol) of DMTMM were
added to the mixture, which was kept under stirring overnight. After removing the solvent under
reduced pressure, the resulting off-white solid residue was treated with 10 wt% of aq. NaOH (10
mL). The suspension thus obtained was filtered, the recovered solid was washed with H2O and
dried under vacuum to give 0.92 g of 3a as a white powder (70% yield).
1H NMR (CDCl3, 298 K) : 7.95 (s, 1H), 7.41-7.26 (m, 5H) 7.24 (br s, 1H), 5.54 (s, 2H), 4.12-3.90
(m, 1H), 3.81-3.59 (m, 2H), 2.70 (br s, 1H, OH), 1.76-1.52 (m, 2H), 0.99 (t, 3H, J=6.9 Hz).
(S)-1-(t-Butyl)-N-(1-hydroxy-4-methylpentan-2-yl)-1H-[1,2,3]-triazol-4-carboxyamide (2b)
According to the above procedure, DMTMM (1.23 g, 4.10 mmol) was added to a solution of (S)-
(+)-2-amino-4-methyl-1-pentanol (0.49 g, 4.20 mmol) and 1b (0.70 g, 4.14 mmol) in acetonitrile
(40 mL). Workup as for 2a gives the sought amide as a white solid (0.79 g, 71% yield).

6
1H NMR (CDCl3, 298 K) : 8.14 (s, 1H), 7.21 (br d, 1H, J=8.6 Hz, NH), 4.23 (m, 1H), 3.77 (dd,
1H, J=11.1 and 3.6 Hz), 3.64 (dd, 1H, J=11.1 and 6.2 Hz), 2.83 (br s, 1H, OH), 1.72 (m, 1H), 1.69
(s, 9H), 1.63-1.34 (m, 2H), 0.95 (d, 6H, J=6.5 Hz).
(S)-1-(t-Butyl)-N-(1-hydroxy-3,3-dimethylbutan-2-yl)-1H-[1,2,3]-triazol-4-carboxyamide (2c)
According to the above procedures, DMTMM (1.94 g, 7.00 mmol) was added to a solution of (S)-
(+)-2-amino-3,3-dimethylbutanol (0.82 g, 7.00 mmol) and 1b (1.20 g, 7.00 mmol) in acetonitrile
(40 mL). Workup as for 2a allows to obtain the sought amide as a white solid (1.51 g, 81% yield).
1H NMR (CDCl3, 298 K) : 8.14 (s, 1H), 7.34 (br d, 1H, J=8.6 Hz, NH), 4.09-4.00 (m, 1H), 4.00-
3.88 (m, 1H), 3.66 (m, 1H), 2.71 (t, 1H, J=11.0 Hz, OH), 1.68 (s, 9H), 1.02 (s, 9H).
(S)-1-Benzyl-N-(1-chloro-butan-2-yl)-1H-[1,2,3]-triazol-4-carboxyamide (3a)
A solution of SOCl2 (0.9 mL, 12.1 mmol) in dichloroethane (10 mL) was drop wise added to a
suspension of 2a (1.66 g, 6.05 mmol) in dichloroethane (100 mL) under nitrogen at room
temperature. The mixture was heated under stirring at 60 °C for 4 hours to afford a clear pale
yellow solution. Upon cooling at room temperature a white solid precipitates. The liquid phase was
removed in high vacuum to give a off-white powder (1.70 g, 99% yield) which was characterized
by 1H NMR spectroscopy and used in the following step without any further purification.
1H NMR (CDCl3, 298 K) : 7.98 (s, 1H), 7.46-7.36 (m, 5H, arom.) 7.28 (br d, 1H, J=8.0 Hz, NH),
5.57 (s, 2H), 4.38-4.25 (m, 1H), 3.80-3.66 (m, 2H), 1.93-1.52 (m, 2H), 1.0 (t, 2H, J=6.8 Hz).
(S)-1-(t-Butyl)-N-(1-hydroxy-4-methylpentan-2-yl)-1H-[1,2,3]-triazol-4-carboxyamide (3b) The
compound was prepared according to the above procedure (quantitative yield).
1H NMR (CDCl3, 298 K) : 8.13 (s, 1H), 7.18 (br d, 1H, J=8.8 Hz, NH), 4.51 (m, 1H), 3.76 (dd,
1H, J=11.1 and 4.4 Hz), 3.65 (dd, 1H, J=11.1 and 3.9 Hz), 1.70 (s, 9H), 1.80-1.45 (m, 3H), 0.96 (d,
6H, J =6.4 Hz).
(S)-1-(t-Butyl)-N-(1-chloro-3,3-dimethylbutan-2-yl)-1H-[1,2,3]-triazol-4-carboxyamide
(3c)
The compound was prepared according to the above procedures (quantitative yield).
1H NMR (CDCl3, 298 K) : 8.16 (s, 1H), 7.20 (br d, 1H, J=9.6 Hz, NH), 4.29 (ddd, 1H, J=10.5, 9.2
and 3.4 Hz), 3.88 (dd, 1H, J=11.5, and 3.4 Hz), 3.56 (dd, 1H, J=11.5 and 9.2 Hz), 1.70 (s, 9H), 1.04
(s, 9H).
1-Benzyl-((S)-4-ethyl-4,5-dihydrooxazol-2-yl)-1H-[1,2,3]-triazole (4a)

7
Under nitrogen, finely powdered NaOMe (1.00 g) was added to a solution of 3a (0.58 g, 2.00
mmol) in methanol (10 mL). The resulting suspension was heated under stirring at 55 °C for 6
hours, then the solution was cooled to room temperature and taken to dryness under vacuum. The
solid residue was dissolved in dichloromethane (30 mL) and the suspension thus obtained was
extracted with water (4 × 30 mL). The organic phase was dried over MgSO4 and then filtered. The
filtrate was dried under vacuum to afford 0.41 g (81% yield) of ligand 4a as a white solid.
1H NMR (CDCl3, 298 K) : 7.89 (s, 1H), 7.40-7.25 (m, 5H), 5.55 (s, 2H). 4.49 (dd, 1H, J=9.3 and
8.1 Hz,), 4.16-4.26 (m, 1H), 4.02-4.07 (m, 1H), 1.51-1.58 (m, 2H), 0.98 (t, 3H, J=7.4 Hz).
13C NMR (CDCl3, 298 K) : 157.0, 138.0, 133.92, 128.5, 129.2, 129.4, 124.9, 72.5, 68.1, 54.7,
28.6, 10.2.
M.p.: 86 °C. Elemental analysis: C14H16N4O (256.30), calcd. C, 65.61; H, 6.29; N, 21.86; found: C,
65.4; H, 6.4; N, 21.8.
GC-MS: 256 [M]+, 227 [M - C2H5]+, 156, 106, 91.
[]D25 = - 20.0 (c = 1, CH2Cl2).
IR (KBr, cm-1): 3070 (m), 2952 (ms), 1672 (s), 1544 (ms), 1454 (s), 1046 (s), 1004 (ms), 883 (m),
713 (s).
1- tert-Butyl-4-( (S)-1- 4-isobutyl-4,5-dihydrooxazol-2-yl)-1H-1,2,3-triazole (4b)
The compound was obtained as a pale yellow oil according to the above procedure (76 % yield).
1H NMR (CDCl3, 298 K) : 8.04 (s, 1H), 4.47 (dd, 1H, J=9.3 and 8.1 Hz), 4.25 (m, 1H), 3.97 (t,
1H, J=8.1 Hz), 1.75 (m, 1H), 1.62 (m, 1H) 1.61 (s, 9H), 1.38 (m, 1H), 0.89 (t, 6H, J=6.5 Hz).
13C NMR (CDCl3, 298 K) : 157.1, 136.8, 122.5, 73.2, 64.9, 60.0, 45.4, 29.9 (2C), 25.4, 22.7, 22.6.
Elemental analysis: C13H22N4O (250.34), calcd.: C, 62.37; H, 8.86; N, 22.38; found: C, 62.2; H,
8.9; N, 22.4.
GC-MS: 250 [M]+, 193 [M – C4H9]+, 126, 124, 57.
[]D25 = - 41.1 (c = 1.1, CH2Cl2).
IR (KBr, cm-1): 2959 (s), 1664 (s), 1556 (w), 1470 (w), 1372 (m), 1226 (ms), 1150 (m), 1041 (ms),
940 (w), 826 (w), 699 (w).
2-tert-butyl-4-((S)-4-tert-butyl-4,5-dihydrooxazol-2-yl) -1H-1,2,3-triazole (4c)

8
The title compound was prepared according to the above procedures (85% yield).
1H NMR (CDCl3, 298 K) : 8.09 (s, 1H), 4.35 (dd, 1H, J=10.1 and 8.7 Hz), 4.22 (t, 1H, J=8.4 Hz),
4.02 (dd, 1H, J=10.1 and 8.1 Hz), 1.67 (s, 9H), 0.93 (s, 9H).
13C NMR (CDCl3, 298 K) : 157.2, 137.0, 122.5, 76.3, 68.9, 60.1, 34.0, 30.1 (3C), 26.1.
M.p.: 132 °C. Elemental analysis: C13H22N4O (250.34), calcd.: C, 62.37; H, 8.86; N, 22.38; found:
C, 62.2; H, 8.9; N, 22.4.
GC-MS: 250 [M]+, 193 [M – C4H9]+, 126, 124, 57.
[]D25 = - 46.9 (c = 1, CH2Cl2).
IR (KBr, cm-1): 3111 (w), 3067 (w), 2978 (m), 2864 (w), 1670 (s), 1550 (ms), 1461 (w), 1359 (m),
1290 (w), 1233 (s), 1156 (m), 1042 (m), 1004 (m), 953 (m), 902 (w).
2.3 Synthesis of Pd(II) allyl complexes
As an example, we report the details relevant to the synthesis of Pd1a.
[Pd(3-C3H5)(4a)](ClO4) (Pd1a)
Under inert atmosphere, a methanol solution of AgClO4 (0.16 g, 0.80 mmol in 20 mL) was drop
wise added to a dichloromethane solution of [Pd(3-C3H5)Cl]2 (145 mg, 0.40 mmol in 20 mL).
The precipitated AgCl was filtered off through celite, then a CH2Cl2 solution of ligand 4a (0.20 g,
0.80 mmol in 20 mL) was added to the filtrate. The resulting pale yellow solution was stirred for 1
hour under inert atmosphere, then the solvent was evaporated under reduced pressure. The obtained
solid was dissolved in a few mL of CH2Cl2. Addition of Et2O afforded Pd1a (0.32 g, 81 % yield) as
a pale yellow microcrystalline solid.
1H NMR (CDCl3, 298 K) : 8.83 (s, 1H), 7.42-7.36 (m, 5H, arom.), 5.68 (s, 2H, CH2), 5.66 (quintet,
1H, J=11.7 Hz, allyl central), 4.91-4.85 (t, 1H, CH2 oxaz), 4.61-4.47 (overlapping broad m, 3H,
allyl-syn and CH oxazoline), 3.38-3.16 (br m, 2H, allyl-anti), 1.82-1.64 (m, 2H), 0.93 (t, J=7.0 Hz,
3H).
13C NMR (CDCl3, 298 K) : 163.2 (1C), 136.4 (1C), 133.4 (1C), 129.4 (2C), 129.2 (2C), 128.4
(1C), 126.7 (1C), 116.1 (1C, HC-allyl), 75.9 (1C), 65.5 (1C), 62.5 (1C, H2C-allyl), 60.5 (1C, H2C-
allyl), 55.5 (1C), 27.6 (1C), 8.5 (1C).
M.p.: 99 °C (dec.). Elemental analysis: C17H21ClN4O5Pd (502.02), calcd. C, 40.57; H, 4.21; N,
11.13; found: C, 40.1; H, 3.96; N, 10.9.
ESI-MS (m/z): calcd. for C17H21N4OPd ([Pd(3-C3H5)(4a)]+): 403.075, found: 403.070.
 (1×10-3 M in acetone): 122 (-1 cm2 mol-1).

9
IR (KBr, cm-1): 3080 (s), 3029 (w), 2975 (w), 2940 (w), 2870 (w), 1753 (vw), 1657 (s), 1570 (s),
1499 (w), 1467 (m), 1458 (m), 1435 (s), 1296 (w), 1258 (m), 1137 (w), 1077 (m), 940 (w), 883
(vw), 718 (s), 690 (m), 553 (w).
[Pd(3-C3H5)(4b)](PF6) (Pd1b)
1H NMR (CDCl3, 298 K) : 8.35 (s, 1H), 5.66 (quintet, 1H, J= 6.5 Hz, allyl central), 4.92 (t, 1H,
J=9.0 Hz), 4.44 (t, 1H, J=7.2 Hz), 4.40-4.25 (br overlapping m, 3H, allyl-syn and CH-oxaz), 3.27
(br m, 2H, allyl-anti), 1.85-1.60 (m, 2 H), 1.74 (s, 9H), 1.54-1.41 (m, 1H), 0.96 (dd, 6H, J=10.6 and
5.6 Hz).
13C NMR (CDCl3, 298 K) : 164.0 (1C), 136.3 (1C), 123.8 (1C), 115.7 (HC-allyl), 63.6 (1C), 63.3
(1C), 61.6 (br, H2C-allyl), 61.00 (br, H2C-allyl), 44.9, 29.7 (3C), 25.2 (1C), 23.4 (1C), 22.0 (1C).
M.p.: 98°C (dec.). Elemental analysis: C16H27F6N4OPPd (542.8), calcd. C, 35.4; H, 5.01; N, 10.32;
found: C, 35.2; H, 4.96; N, 10.6.
ESI-MS (m/z): calcd. for C16H27,N4OPd ([Pd(3-C3H5)(4b)]+): 397.122, found: 397.140.
 (1×10-3 M in acetone) = 102 -1cm2mol-1.
IR (KBr, cm-1): 2970 m, 1670 s, 1469 m, 1424 m, 1377 m, 1238 m, 1190, 1071, 841 vs, 558 vs.
[Pd(3-C3H5)(4c)](ClO4) (Pd1c)
1H NMR (CDCl3, 298 K) : 8.48 (s, 1H), 5.73 (br m, 1H, HC-allyl), 4.87 (t, 1H, J=9.5 Hz), 4.79 (dd,
1H, J=9.2 and 4.9 Hz), 4.47 (br s, 2H, CH2 syn), 4.20 (dd, 1H, J=9.7 and 4.9 Hz), 3.48 (br d, 1H,
CH anti, J=12.0 Hz), 3.22 (br d, 1H, CH anti, J=9.8 Hz), 1.78 (s, 9H, t-bu), 1.02 (s, 9H, t-bu).
13C NMR (CDCl3, 298 K) : 164.5 (1C), 136.5 (1C), 123.9 (1C), 116.1 (1C, HC-allyl), 74.3 (1C),
73.6 (1C), 63.8 (br, 1C, H2C-allyl), 63.7 (1C), 62.3 (br, 1C, H2C-allyl), 34.9 (1C), 29.8 (3C), 25.9
(3C).
Mp.: 120 °C (dec.). Elemental analysis: C16H27ClN4O5Pd (496.07), calcd. C, 38.64; H, 5.47; N,
11.27; found: C, 38.4; H, 5.66; N, 11.5.
ESI-MS (m/z): calcd. for C17H27N4OPd ([Pd(3-C3H5)(4c)]+): 397.122; found 397.119.
 (1×10-3 M in acetone) = 137 -1 cm2 mol-1.
IR (KBr, cm-1): 2964 s, 1656 s, 1478 s,1427 s, 1241, vs, 1193, 1047 vs, 926, 623 vs.
2.4 Synthesis of [PdCl(µ-Cl)(L)]2 (Pd2a-b)
As an example we report the details relevant to the synthesis of Pd2a.
[PdCl(µ-Cl)(4a)]2 (Pd2a)

10
Ligand 4a (0.13 g, 0.50 mmol) was added portion wise to a suspension of [PdCl2(CH3CN)2] (0.13 g,
0.50 mmol) in dichloromethane (20 mL). The resulting solution was stirred under inert atmosphere
at room temperature for 20 hours. The orange solution was concentrated in high vacuum to give an
orange solid, that was recrystallized from dichloromethane with diethyl ether. Pd2a was recovered
as a yellow microcrystalline powder (0.17 g, 80% yield).
1H NMR (CDCl3, 298 K) : 7.84 (s, 1H, CH try), 7.48-7.37 (m, 5H, arom.), 5.65 (d, 1H, J=15.0 Hz,
HHC), 5.62 (d, 1H, J=15.0 Hz, HHC), 5.10 (t, 1H, J=9.1 Hz), 4.62 (dd, 1H, J=5.1 and 8.3 Hz),
4.45-4.34 (br m, 1H), 2.17-2.00 (br m, 1H), 1.97-1.80 (m, 1H), 0.92 (t, 1H, J=7.2 Hz).
13C NMR (CDCl3, 298 K) : 163.8, 137.1, 131.5, 130.1, 129.8, 129.5, 125.9, 71.0, 63.7, 56.80, 27.3,
26.6, 8.6.
M.p.: 258 °C (dec.). Elemental analysis: C28H32Cl4N8O2Pd2 (867.26), calcd. C, 38.78; H, 3.72; N,
12.92; found: C, 39.07; H, 3.92; N, 13.14. MW (VPO, CHCl3): 753.
+
ESI-MS (m/z). Calcd. for C28H32Cl3N8O2Pd2 : 830.979 ([M-Cl-]+); found 830.987.
IR (KBr, cm-1): 3080 (s), 3029 (w), 2975 (w), 2940 (w), 2870 (w), 1753 (vw), 1657 (s), 1570 (s),
1499 (w), 1467 (m), 1458 (m), 1435 (s), 1296 (w), 1258 (m), 1137 (w), 1077 (m), 940 (w), 883
(vw), 718 (s), 690 (m), 553 (w).
[PdCl(µ-Cl)(4b)]2 (Pd2b).
Following the above procedure complex Pd2b was obtained as an orange microcrystalline powder
in 77 % yield.
1H NMR (CDCl3, 298 K) : 8.08 (s, 1H), 5.18 (t, 1H, J=8.8 Hz), 4.55 (t, 1H, J=8.4) 4.49-4.39 (m,
1H), 2.38 (t, 2H, J=13.0 Hz) 1.73 (s, 9 H), 1.64-1.41 (m, 2H) 1.00-0.90 (m, 6H).
13C NMR (CDCl3, 298 K) : 163.9, 136.7, 123.2, 78.9, 63.9, 61.8, 43.1, 29.8 (3C), 25.6, 23.7, 21.4.
M.p.:198°C (dec). Elemental analysis: C26H44Cl4N8O2Pd2 (855.33), calcd. C, 36.51; H, 5.19; N,
13.10; found: C, 36.7, H, 5.4; N, 13.2. MW (VPO; CHCl3) : 725.
+
ESI-MS (m/z): calcd. for C26H44Cl3N8O2Pd2 : 819.073 ([M-Cl-]+); found 819.087.
IR (KBr, cm-1): 2959 (ms), 2864 (m), 1657 (s), 1575 (s), 1474 (m), 1429 (m), 1378 (m), 1246 (ms),
1201 (m), 1074 (m), 934 (w), 693 (w), 560 (w).
[PdCl(µ-Cl)(4c)]2 (Pd2c).
Following the above procedure complex Pd2c was obtained as an orange microcrystalline powder
in 72 % yield.
1H NMR (CDCl3, 298 K) : 9.85 (s, 1H), 4.63-4.47 (2 overlapping m, 2H), 4.34 (dd, J=9.7 and 5.8
Hz), 1.51 (s, 9H), 1.26 (s, 9H).

11
13C NMR (CDCl3, 298 K) : 161.9, 134.4, 128.6, 75.6, 70.3, 60.8, 53.6, 34.7, 29.9 (3C), 26.4 (3C).
M.p.: 200 °C (dec.). Elemental analysis: C26H44Cl4N8O2Pd2 (855.33) [M-Cl-]+; calcd. C, 36.51; H,
5.19; N, 13.10; found: C, 36.3, H, 5.5; N, 13.3. MW (VPO; CHCl3): 760.
+
ESI-MS (m/z). Calcd. for C26H44Cl3N8O2Pd2 : 819.073 ([M-Cl-]+); found 819.088.
IR (KBr, cm-1): 2972 (br s), 1651 (s), 1563 (s), 1480 (ms), 1435 (ms), 1397 (m), 1366 (ms), 1246
(s), 1188 (ms), 1080 (s), 927 (mw), 826 (w) 738 (mw) 693 (w), 560 (w).
2.5 Synthesis of [PdCl2(L)2] (Pd3a-b)
As an example we report the details relevant to the synthesis of Pd3a.
[PdCl2(4a)2] (Pd3a).
Ligand 4a (0.26 g, 1.00 mmol) was added portion wise to a suspension of [PdCl2(CH3CN)2] (0.13 g,
0.50 mmol) in dichloromethane (20 mL).
The resulting solution was stirred under inert atmosphere at room temperature for 6 hours. The
orange solution was concentrated in high vacuum to give an orange solid, that was recrystallized
from dichloromethane with diethyl ether. Pd3a was recovered as a yellow microcrystalline powder
(0.27 mg, 79% yield).
1H NMR (CDCl3, 298 K) : 9.85 (s, 1H, CH try), 7.51-7.27 (m, 5H, arom.), 5.70 (s, 1H, HHC), 4.65
(t, 1H, J=9.1 Hz), 4.48 (dd, 1H, J=3.8 and 9.1 Hz), 4.27 (t, 1H, J=8.5 Hz), 2.87 (br m, 1H), 2.09 (m,
1H), 1.14 (t, 1H, J=7.2 Hz).
13C NMR (CDCl3, 298 K) : 163.8, 134.6, 129.1 128.9, 128.3, 128.1, 125.3, 72.3, 67.8, 54.4, 28.0,
9.6.
M.p.: 210 °C (dec.). Elemental analysis: C28H32Cl2N8O2Pd (689.93), calcd. C, 48.74; H, 4.67; N,
16.24; found: C, 48.42; H, 4.95; N, 16.44.
ESI-MS (m/z): calcd. for C28H32ClN8O2Pd+: 653.137 ([M-Cl-]+); found: 653.128.
IR (KBr, cm-1): 3118 (w), 3086 (w), 2959 (mw), 2930 (w), 2883 (vw), 1676 (s), 1664 (s); 1556 (m),
1462 (m), 1385 (w), 1233 (ms), 1207 (m), 1023 (mw), 956 (w), 718 (s), 689 (w), 541 (vw).
[PdCl2(4b)2] (Pd3b)
Following the above procedure complex Pd3b was obtained as a dark yellow microcrystalline
powder in 68% yield.
1H NMR (CDCl3, 298 K) : 9.51 (s, 1H, CH try), 4.68 (t, 1H, J=8.8 Hz), 4.64-4.51 (m, 1H), 4.24 (t,
1H, J=7.8 Hz), 3.08 (br m, 1H), 1.94 (br m, 1H), 1.74 (s, 9H), 1.12 (d, J=6.6 Hz, 3H).
13C NMR (CDCl3, 298 K) : 160.1, 134.1, 127.0, 73.4, 65.3, 60.8, 45.0, 30.1, 25.9, 23.9, 22.1.

12
M.p.: 221 °C (dec.). Elemental analysis: C26H44Cl2N8O2Pd (678.01), calcd. C, 46.06; H, 6.54; N,
16.53; found: C, 45.92; H, 6.87; N, 16.819.
ESI-MS (m/z): calcd. for C26H44ClN8O2Pd+: 641.231 ([M-Cl-]+); found: 641.228.
IR (KBr, cm-1): 3144 (m), 2959 (br s), 1676 (s), 1651 (s), 1556 (ms), 1467 (m), 1416 (s), 1372 (s),
1302 (m), 1238 (s), 1194 (ms), 1175 (ms), 959 (m), 839 (w), 737 (mw), 699 (mw), 601 (w), 528
(w).
[PdCl2(4c)2] (Pd3c)
Following the above procedure complex Pd3c was obtained as a dark yellow microcrystalline
powder in 72% yield.
1H NMR (CDCl3, 298 K) : 9.81 (s, 1H, CH try), 4.65-4-55 (m, 2H), 4.35 (dd, J=10.3, 5.9 Hz, 1H),
4.24 (t, 1H, J=7.8 Hz), 1.52 (s, 9H), 1.30 (s, 9H).
13C NMR (CDCl3, 298 K) : 161.9, 134.3, 128.4, 75.5, 70.3, 60.7, 34.6, 29.8, 26.4.
M.p.: 240 °C (dec.). Elemental analysis: C26H44Cl2N8O2Pd (678.01), calcd. C, 46.06; H, 6.54; N,
16.53; found: C, 45.8; H, 6.85; N, 16.79.
ESI-MS (m/z): calcd. for C26H44ClN8O2Pd+ : 641.231 ([M-Cl-]+); found 641.241.
IR (KBr, cm-1): 3137 (w), 2966 (m), 1639 (ms), 1544 (m), 1480 (w), 1372 (ms), 1277 (ms), 1265
(s), 1169 (w), 1042 (m), 959 (w).
2.6 X-Ray structure determination and refinement
Crystals suitable for the X-ray experiment of Pd3c and Pd2d were obtained by slow diffusion of
diethyl ether into a dichloromethane solution (Pd3c, orange prisms) or by slow evaporation of
dichloromethane solutions (Pd2d, orange needles). In the case of Pd3c, a fragment of irregular
shape was cut from a small prism. The selected specimens were fastened on the goniometer head of
an Oxford Diffraction Gemini diffractometer. The instrument was equipped with a 2K × 2K EOS
CCD area detector and sealed–tube Enhance (Mo) and (Cu) X–ray sources. Data collection were
performed with the ω–scans technique at 300(1) K for Pd3c, and 297.4(6) K for Pd2d, using
graphite–monochromated MoKα (A, λ = 0.71073) and CuKα (B, λ = 1.54184) radiation in a 1024 ×
1024 pixel mode and 4 × 4 (Pd3c) or 2 × 2 (Pd2d) pixel binning. Intensities were corrected with
respect to absorption, Lorentz and polarization effects. An empirical multi–scan absorption
correction based on equivalent reflections was performed with the scaling algorithm SCALE3
ABSPACK. Unit cell parameters were determined by least–squares refinement of 11690 (Pd3c) and
858 (Pd2d) reflections chosen from the whole experiment. Data collection, reduction and
refinalization were performed with the CrysAlis Pro software suite [CrysAlisPro, Version
1.171.38.46 (Rigaku OD, 2015).]. The structures were solved using SHELXT [19] and refined by

13
2
full–matrix least–squares methods based on Fo with SHELXL [20] in the framework of the OLEX2
software [ 21].
The structure of Pd3c has been solved in the non-centrosymmetric P 41212 space group, by means
of the heavy atom methods. The structure of Pd2d was instead solved by means of intrinsic phasing
in the P-1 space group. In Pd3c, the asymmetric unit is given by half of the molecule. The refined
value of the Flack parameter [22-24] was 0.001(14), suggesting a correct absolute structure. Both
structures are affected by a little disorder. In Pd3c, atoms affected are C6 and C7; in Pd2d, atoms
involved are C4 and C5. The alternate positions of these atoms and of bounded H atoms were
refined with site occupation factors constrained to sum to unity. Refined sofs for alternate positions
were 0.413/0.587 in Pd3c and 0.253/0.747 in Pd2d. All non-hydrogen atoms were refined
anisotropically; H atoms were refined as “riding model”. Other SHELX [19] restraints (RIGU) were
also applied to improve the models.
The refinement of the structure of Pd2d was hampered by some limitations (see Supporting
Information) and the final R value did not drop below ca. 12% (3.71% for Pd3c). However, the
chemical identity of the crystallized product does not look in question. Since the main purpose of
the structural determination was to identify the molecular structure of the complex, we considered
the proposed solution acceptable and we terminated the refinement of Pd2d, at this stage. The
crystallographic data for Pd2d and Pd3c have been deposited at the Cambridge Crystallographic
Data Center as .cif files, with CCDC numbers 1943819 and 1943820, respectively. The data can be
obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif.
2.7 Computational details
The geometry optimizations and energy calculations were carried out using the range-
separated DFT functional ωB97X [25-27] in combination with the split-valence polarized basis set
of Ahlrichs and Weigend, with Dolg’s and co-workers ECP for the palladium centre [28,29]. The
implicit solvation model C-PCM was added considering acetonitrile as continuous medium [30,31].
The “restricted” formalism was always applied. The stationary points were characterized by
vibrational analysis, from which zero-point vibrational energies and thermal corrections (T= 298.15
K) were obtained [32]. Calculations were performed with Gaussian 09 [33], running on an Intel
Xeon-based x86-64 workstation. The software Multiwfn (version 3.5) was used for population
analyses [34]. Cartesian coordinates of the DFT-optimized structures are collected in a separated
file.

14
3. Results and Discussion
3.1. Ligands synthesis
The approach developed to synthesize the new triazolyl-oxazoline ligands 4a-c is outlined in
Scheme 2.
R1
R
OH
O
R
SOCl2
H2N
N
N
R1
N
N
COOH
N
HN
N
DMTMM
OH
1a: R = Bn
1b: R = t-Bu
2a: R = Bn, R1= Et
2b: R = t-Bu, R1= i-Bu
2c: R = t-Bu, R1= t-Bu
R
R
O
N
O
NaOMe
MeOH
N
R1
N
N
N
N
N
R1
HN
Cl
3a: R = Bn, R1= Et
3b: R = t-Bu, R1= i-Bu
3c: R = t-Bu, R1= t-Bu
4a: R = Bn, R1= Et
4b: R = t-Bu, R1= i-Bu
4c: R = t-Bu, R1= t-Bu
Scheme 2. Synthesis of TryOx ligands 4a-c
Cu(I) catalyzed coupling of benzyl azide or t-butyl azide with either propiolic acid or methyl
propiolate (followed by alkaline hydrolysis) is a prompt entry to prepare in high yield 1-benzyl or 1-
t-butyl-1H-1,2,3-triazole-4-carboxylic acids 1a and 1b, respectively. Then, reaction of 1a,b with
chiral amino alcohols affords amides 2a-c. Some different protocols were tested in order to improve
the yield of this reaction. Best results were achieved using 4-(4,6-dimethoxy[1,3,5]triazin-2-yl)-4-
methyl-morpholinium chloride (DMTMM) a stereoselective amine-carboxylic acid coupling agent
[35,17]. Almost quantitative yields are achieved working at room conditions in acetonitrile,
purification is simply performed by rotoevaporation of the reaction mixture followed by extraction
of the residues of the coupling agent with an aqueous base.
While direct cyclization of 2a-c to 4a-c affords the target compounds in low yields (about
20% after chromatographic purification), the two step sequence developed by Stoltz for the
synthesis of chiral PyOxs [5] turned out to be very efficient. Specifically, Stoltz’s synthetic
approach entails: i) chlorination of the amide-alcohol with SOCl2, and, ii) ring closure in the
presence of a base. Key features are: i) the chlorination step occurs quantitatively and does not
requires any purification procedure; and, ii) the ring closure proceeds with complete retention of the

15
configuration at the chiral center, best yields being obtained in methanol using strong bases (e.g.
25% NaOMe). No particular problem arose in applying Stoltz’s protocol to TryOxs synthesis; in
fact, treatment of amide-alcohols 2a-c with SOCl2 gave chlorides 3a-c quantitatively, then,
treatment of 3a-c with 10% NaOMe in methanol followed by a minimum workup allowed to obtain
the sought ligands 4a-c in 75-85% yields. Ligands 4a-c were characterized by elemental analysis,
1
1
IR, GC-MS, H and 13C NMR spectroscopies. In particular, in the H NMR spectra the triazole
proton appears as a low field singlet in the 7.89 - 8.09 range, while the protons of the oxazoline
furnish three separate signals in the 4.5 – 3.8 ppm range. The relative data are reported in the
Experimental section and do not deserve particular comments.
3.2. Palladium(II) complexes synthesis
3.2.1 Synthesis of Pd(II)-allyl complexes
For a first preliminary evaluation of the coordination capability of ligands 4a-c, we choose to study
the reactivity of the new ligands towards [Pd(3-C3H5)Cl]2 in the endeavor of synthesize the
corresponding Pd(II)-allyl complexes (see Scheme 3).
R
O
N
N
N
N
R1
Pd
Solv
Solv
R1
Pd
N N
N
N
O
R
Scheme 3. Synthesis of palladium-allyl-TryOx complexes
As a matter of fact, nowadays palladium based catalytic processes have gained an exceptional
importance in chemical synthesis and particularly in cross-coupling reactions. Among the almost
infinite number of species which can be used as the catalyst or the precatalysts in palladium-
catalyzed cross-coupling reactions, palladium-allyl complexes of the type [PdX(η3-allyl)(L)] (X:
anion) have a privileged position because of their stability, well established structure, and certainty
of composition [36]. Moreover, the peculiar nature of the -allyl moiety allows to use it as

16
coordination reporter, for instance enabling to establish through space correlations by 2D NMR
techniques.
The palladium-allyl complexes Pd1a-c are promptly obtained by treating [Pd(3-C3H5)Cl]2 with a



silver salt (AgX: X = BF4 , ClO4 , PF6 ) in dichloromethane; filtration of precipitated AgCl
followed by addition of the ligand (Scheme 3) leads to pale yellow solutions from which the sought
allyl complexes are recovered by precipitation with diethyl ether. Elemental analyses agree with the
proposed formulation; in the ESI-MS spectra the most important peaks correspond to the cations
[[Pd(3-C3H5)(4a-c)]+, the isotope patterns being in good agreement with the calculated ones. The
M of 103 M solutions of these species in acetone are in the 120-150 1 cm2 mol1 range
confirming that these species are 1:1 electrolytes [37].
1
In the H and 13C NMR spectra of complexes Pd1a-c there are present two distinct sets of
resonances which are promptly attributed to the coordinated ligand and the allyl moiety,
respectively.
Comparison of the NMR chemical shifts of free and coordinated 4a-c resonances indicates that they
behave as N,N-chelating ligands. Coordination of the triazolyl moiety is demonstrated by a
downfield shift of 0.4 – 0.8 ppm of the resonance due to the triazole ring proton, and coordination
of the oxazoline ring is proved by a downfield shift of about 0.5 ppm of all the oxazoline protons.
Upon coordination to palladium, the 13C NMR the signal due to the C-H of triazole is shifted
downfield of about 1.3-1.8 ppm, this effect is accompanied by an upfield shift of the triazole
quaternary carbon resonance which is of only about 0.5 ppm for Pd1b,c but as large as 2.0 ppm for
Pd1a.
1
In the H NMR spectra, the signals relevant to the allyl moiety are displaced to lower fields and
become broad indicating dynamic behavior. In all cases, the syn protons give a single broad
resonance, while the resonances relevant to anti protons appear as two broad distinct signals.



Although some different counterions (BF4 , ClO4 , PF6 ) were employed, we didn’t succeed in
obtaining single crystals suitable for X-rays analysis; thus, DFT calculations were performed in
order to get some deeper insights on the structural features of the allyl-complexes. The DFT-
optimized structures of Pd1a and Pd1c are depicted in Figure 1, while a selection of computed
bond lengths and angles is reported in the caption. The introduction of different substituents on the
heterocycles causes negligible variations of the Pd-Callyl bond lengths. The Pd-N2(triazole) (see
Scheme 1 for atom numbering) distance is roughly the same in the two compounds, while the Pd-
N(oxazoline) bond length is slightly longer in Pd1c, probably because of the higher steric bulk of
the t-butyl substituent with respect to the ethyl one. As expected, no stationary points were found

17
trying to optimize the geometry of isomers where the ligands are coordinated by the oxazoline
nitrogen and the triazole N3.
((INSERT FIGURE 1))
3. 2.2 Synthesis of [PdCl(µCl)(L)]2 (Pd2a-b)
The picture which comes to light when TryOxs are allowed to react with species of the type
[PdCl2L2] (L = labile ligand such as CH3CN, BnCN or even S(CH3)2) is more intriguing; for the
sake of clarity the results of our investigations are gathered in Scheme 4.
Cl
Cl
Pd
Et
N
N
N
N
O
Bn
Pd2d
Crystallization
when TryOx = 4a
R1
R
N
N
N
O
N
R
[PdCl2(CH3CN)2]
CH2Cl2
O
N
Cl
Cl
N
N
N
Pd
Pd
N
R1
Cl
N
Cl
O
N
4a-c
N
R1
R
Pd2a-c
R
O
N
N
N
N
R1
R1
O
N
R
N
N
N
Cl
Pd
N
Cl
N
N
R
Pd3a-c
N
O
R1
Scheme 4. Synthesis of palladium(II)-TryOx-chloro complexes
Treatment of [PdCl2(CH3CN)2] with 1:1 equimolecular amounts of TryOxs 4a-c in dichloromethane
at room temperature affords compounds having elemental analyses in agreement with the
formulation [PdCl2(4a-c)]. The compounds are soluble in organic solvent such as dichloromethane,
chloroform, tetrahydrofuran and they are non-conducting in acetone or chloroform.
1
In contrast with that found in the case of the cationic allyl complexes, H NMR spectroscopy
indicates that in these species TryOxs behaves as monodentate ligands coordinating to palladium

18
through the N atom of the oxazoline. Taking complex Pd2a as a representative example, we found
that the chemical shift of the resonance due to the proton on the triazole ring is almost unaffected
with respect to that of the free ligand ((CH)comp = 7.83 vs (CH)free = 7.88); on the contrary, all the
resonances due to the oxazoline ring were found to give multiplets centered at 5.10, 4.60 and 4.39 
that are significantly downfield shifted with respect the corresponding resonances of the free ligand
centered at 4.44, 4.12 and 3.92 , respectively; the 1H NMR spectra of Pd2b and Pd2c present the
analogous features. The higher -donor ability of the oxazoline ring with respect to triazole was
confirmed by the charge distribution of the ligands. The partial charge of oxazoline N in 4a is -
0.205 a.u., while that of triazole N2 is -0.152 a.u. In the case of 4c the corresponding values are -
0.198 and -0.155 a.u. The Hirshfeld population analyses supported this conclusion, the oxazoline N
and triazole N2 partial charges being -0.233 and -0.162 a.u. in 4a and -0.220 and -0.166 a.u. in 4c.
The key indication on the nature of Pd2a-c in solution came from their ESI-MS. As a matter of fact,
the unique clusters of signals observable in these spectra correspond to cations of formulation
[(TryOx)2Pd2Cl3]+ suggesting that Pd2a-c are dimeric species (see Scheme 4) with two chlorine
atoms bridging two (TryOx)PdCl units. The dimeric nature of Pd2a-b was definitely confirmed by
determining their molecular masses in solution by Vapour Phase Osmometry.
These experimental findings are quite surprising taking into account the N,N chelating ability of
TryOxs observed in the case of the above reported cationic allyl complexes; accordingly, we were
intrigued to isolate crystalline samples of Pd2a-c suitable for X-ray diffraction analysis.
Eventually our efforts succeeded and slow evaporation of dichloromethane solutions of Pd2a
allowed to obtain orange needles, designated as Pd2d in Scheme 4, that were found suitable for X-
ray structural studies.
3.2.3 X–ray Crystal Structure of [PdCl2(4a)] Pd2d
Summaries of crystal and structure refinement data for Pd2d are listed in Table I; some selected
structural parameters are reported in Table II. In the latter, data for complex Pd2d must be regarded
as preliminary.
((INSERT FIGURE 2))
Figure 2 shows the ORTEP [38] representation of Pd2b, with the chosen numbering scheme,
with highlighted alternate positions for disordered atoms.
As noted in the Experimental section, the refinement procedure for [PdCl2(4a)] was
terminated when the final R index was still above 12%. In our opinion, this value is too high to

19
allow a discussion of the structural parameters of the molecule; hence, such discussion will not be
carried over at this stage. This also apply to the disorder of the ethyl residue branching at the chiral
C(3), which could hint to the possible presence of both enantiomers of the ligand. Attempts of
refining the structure in the P1 space group (two molecules in cell) failed in the very early stages of
the refinement, with coordinates of corresponding atoms in two independent molecules showing
strong correlations, thus compelling us to perform refinement in the P-1 space group. Available data
hence do not allow to confirm or reject the presence in the solid state of only one ligand enatiomer,
yet are sufficient to confirm the chemical identity of the crystallized compound and the basic
arrangement of the molecule, which is briefly outlined hereafter. Complex Pd2d is mononuclear
and neutral when in the solid state. The Pd atom is bound by two chlorides and two nitrogen atoms
of the chelating ligand, in a square planar environment. Upon coordination, the triazolyloxazoline
ligand makes with Pd a five-membered metallacycle (N(1), C(1), C(7), N(2), Pd), with all atoms
nearly coplanar. The oxazoline and triazolyl rings of the ligand also appear nearly planar. The
triazolyl ring shows a slight deviation towards an envelope arrangement (with N(2) at the flap). A
similar arrangement might also be expected for the partially saturated oxazoline ring, but it did not
emerge at the present stage of the refinement. The mean planes encompassing the oxazoline and
triazolyl rings do not perfectly coincide with the mean plane of the metallacycle, so that the
molecule is slightly puckered overall (with the mean planes of oxazoline and of the triazolyl
moieties bent towards each other and making a dihedral angle of about 5°). As for the benzyl
residue branching at N(4), the mean plane of the phenyl ring and the mean plane of the metallacycle
make with each other a dihedral angle of about 75°.
An inspection of the CCDC repository (Cambridge Structural Database, Version 5.40 of November
2018 + 3 updates) [39] for compounds having similar triazolyloxazoline ligands returned only five
entries described in two papers [11,40]. Of these, one is a copper(II) compound, [11] containing two
2-(1-benzyl-1H-1,2,3-triazol-4-yl)-4,5-dihydrooxazole ligands, very similar to Pd3c discussed
below, and three are iridium complexes of a modified benzooxazoline ligand [40]. Hence, to the
best of our knowledge, this is the first report of a Pd(II) triazolyloxazoline complex.
According to the contrasting molar masses data in solution and the X-ray structure, we must
conclude that while in solution Pd2a is a dimeric species in which the TryOx behaves as a
monodentate ligand employing the N atom of the oxazoline, in the solid state, upon crystallization,
it converts into Pd2d a mononuclear species in which the TryOx behaves as a N,N bidentate
chelating ligand.
3..2.4 Synthesis of [PdCl2L2] (Pd3a-b)

20
Taking into account the ease with which the chlorine bridge in dimeric Pd2a breaks, we were
prompted to investigate the reactivity of complexes Pd2a-c towards the addition of a second
equivalent of ligand. As a matter of fact we were intrigued to find out if a second molecule of ligand
could cleave the chlorine bridges and the coordination mode adopted by the ligands in the final
product.
Identical compounds of formulation [PdCl2(TryOx)2] (Pd3a-c, see Scheme 4) were obtained either
adding an equivalent of ligand to Pd2a-c or directly allowing to react [PdCl2(CH3CN)2] with two
equivalents of ligand. Analytical data and ESI-MS are in keeping with the proposed formulation
and conductivity measurements showed that complexes Pd3a-c are neutral compounds in
1
13
chloroform or in acetone. A single set of signals is present in both the H and C NMR spectra of
Pd3a-c, indicating that both TryOx ligands are equivalent and hence that they are coordinated to
1
palladium in the same fashion. In the H NMR spectra a remarkable feature is that not only the
oxazoline protons, but also the triazolyl proton resonate at significantly lower fields with respect to
the free ligands. Specifically, the chemical shifts of oxazoline protons are similar to these found in
complexes Pd2a-c pointing at coordination of N atom of the oxazoline, while the triazolyl protons
are found to resonate at very low fields in the 9.85 - 9.51  range, which is even lower than that
found for the cationic complexes Pd1a-c. Rationalization of this puzzling spectral feature came
from X-ray structural studies (see below) which demonstrate that there is a close non-bonding
contact between the H atoms of triazoles and the Cl atoms of the complex.
3.2.5 X–ray Crystal Structure of Pd3c
Slow diffusion of diethyl ether into a dichloromethane solution of Pd3c allowed to obtain
crystalline samples (orange prisms) suitable for X-ray studies. Summaries of crystal and structure
refinement data for complex Pd3c are listed in Table I and some selected structural parameters are
reported in Table II.
At the end of the refinement process the final R index (below 4%) is much better than in [PdCl2(4a)],
leaving no unresolved peaks, especially around the chiral C(3) atom. Figure 3 shows the ORTEP
representation of the compound, with the chosen numbering scheme, with highlighted alternate
positions for disordered atoms.
((INSERT FIGURE 3))

21
Complex Pd3c is mononuclear and neutral. However, opposite to what found for Pd2d, the
triazolyloxazoline ligand does not chelate Pd. Instead, two ligand units act as monodentate donors
(through the N(1) atom) and the coordination environment of Pd is completed by two chloride ions.
In Pd3c, the asymmetric unit consists of half a molecule, so the atoms belonging to the coordination
plane are strictly coplanar by symmetry and the Pd coordination environment has regular square
planar geometry. In the ligand, the atoms of the triazolyl ring are coplanar within 0.01 Å, while the
oxazoline ring is slightly bent towards an envelope arrangement, with the C(2) atom at the flap by
0.08 Å. The position of the tert-butyl residue branching at the chiral C(3) atom is clearly defined, so
it is ascertained that in the crystal structure of [PdCl2(4c)2] only one enantiomer of the ligand is
present. The correct attribution of the absolute structure is supported, as indicated in the
Experimental Section, by the value close to zero (0.001(14)) of the Flack parameter, calculated
from 1576 selected quotients (Parsons' method [24]).
Opposite to what was found in Pd2d, the mean planes encompassing the triazolyl and oxazoline
rings make with the coordination plane dihedral angles of 71.6 and 65.7°, respectively, and they
also make a dihedral angle of 15.8° with each other. The reciprocal arrangement of the mean planes
of the triazolyl and oxazoline moieties in reported compounds is mostly similar to that found in
Pd3c (dihedral angles ranging from 5.4 [11] to 10.6° [40]. Among reported compounds, the entity
most resembling complex Pd3c is the compound described in reference [11], also showing the
metal bound by two monodentate ligands and two chloride ions.
With respect to bond distances in the coordination sphere, a CCDC search for mononuclear Pd(II)
complexes having a PdN2Cl2 square planar environment (480 entries) indicates an average Pd-N,
Pd-Cl distances of 2.020 Å and 2.300 Å, respectively. The values found for Pd3c (Pd-N bond of
2.033(2) Å, Pd-Cl lengths of 2.2913(12) and 2.3329(12) Å) look in agreement with available data.
The difference between the two Pd-Cl bonds (0.042 Å) is a feature that does not appear in the pretty
similar copper(II) complex [11] and points to a rather efficient intramolecular nonbonding
interaction (H····Cl distance of 2.491 Å, about 0.5 Å shorter than the sum of van der Waals radii
involving Cl(1) at one end and H(9) (and its symmetry equivalent at +y,+x,1-z) at the other. As for
the triazolyloxazoline ligand, the values found in Pd3c of bond distances within the rings also look
in reasonable agreement with the corresponding averages for reported compounds. In the triazolyl
residue, the deviation between our data and mean values for corresponding bond lengths is never
larger than 0.03 Å. In the oxazoline moiety there is a greater difference (largest deviation of 0.11
Å), however, most of reported complexes are in fact benzoxazoline derivatives. When looking at
the closely related complex [11], the largest deviation reduces to 0.038 Å. The comparison between
complex Pd3c and available data indicate substantial aromatic behavior in the triazolyl moiety and

22
no involvement in the conjugation of the C(1)-N(1) bond of the oxazoline moiety. The latter retains
instead typical double bond character (1.287(3) Å, almost identical to the average of 1.289 Å for
reported compounds).
Besides to the above mentioned intramolecular contact between Cl(1) and H(9), there are
virtually no intermolecular contacts worth of mention. The two ‘shortest’ nonbonding approaches
(both only 0.05 Å shorter than the sum of the pertinent van der Waals radii loosely involve the
triazolyl N(2) and N(3) atoms, which respectively engage the H(12C) and the H(5B) atoms of a
nearby moiety at 1.5-y, ½+x, ¼+z. These contacts create an helical motif that propagates along with
the crystallographic b axis.
The triazole-H---Cl interaction was also detected in the DFT-optimized structures of Pd3a and
Pd3c by means of Atoms-in-Molecules (AIM) analysis. The (3,-1) bond critical points (b.c.p.) of
interest are depicted in Figure 4 together with the paths connecting the (3,-1) and (3,-3) points and
the interbasin surface. Selected properties at b.c.p. are reported in the Figure. In particular, the
positive values of the Laplacian of electron density 2  are in agreement with electron-unshared
interactions, despite the fact that the very low negative energy density (E) values could suggest a
slightly covalent nature [41].
((INSERT FIGURE 4))
Conclusions
A convenient protocol for the synthesis of triazolyl-substituted chiral oxazolines has been
developed and its efficiency has been demonstrated preparing ligands having bulky and strongly
electron donor substituents.
These ligands display the ability of behave both as bidentate and as monodentate, and that in this
latter case that the preferred coordination site is the oxazoline N atom. Thus it appears that the N
atom of the oxazoline is a better -donor than the N atoms of the triazole. Subtle effects are at play
when deciding the adopted coordination fashion as found in the case of Pd2a → Pd2d
transformation; further investigations are currently in progress on this subject.
Acknowledgements
Ca’ Foscari University of Venice is gratefully acknowledged for financial support (Bando Progetti
di Ateneo 2014, D.R. 553/2014 prot. 31352; Bando Spin 2018, D.R. 1065/2018 prot. 67416).
Conflict of interest

23
The authors declare that there is no conflict of interest regarding the publication of this paper.
Supplementary Information
Details about the X-ray structure refinements and Cartesian coordinates of the DFT-optimized
structures are provided as Supplementary Information file.
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26
Tables
Table I. Crystallographic Data for the complexes Pd3c and Pd2d.
Pd3c
Pd2d
Empirical formula
Formula weight
Temperature/K
Crystal system
Space group
a / Å
C26H44Cl2N8O2Pd
C14H16N4OCl2Pd
433.61
677.99
300(1)
297.4(6)
Tetragonal
triclinic
P 41 21 2
P-1
9.0141(13)
7.1612(14)
8.8314(15)
13.744(3)
97.653(17)
104.208(19)
90.541(14)
834.3(3)
b / Å
9.0141(13)
c / Å
39.596(8)
α / °
90
β / °
90
γ / °
90
Volume /Å3
Z
3217.3(11)
4
2
ρcalc Mg / m3
μ / mm-1
1.400
1.726
0.779
11.972
F(000)
1408.0
432.0
Crystal size/mm3
Reflections collected
Independent reflections / Rint
Data/restraints/parameters
Goodness-of-fit a on F2
Final R indexes [I > 2σ (I )]
0.26 × 0.21 × 0.16
75000
0.50 × 0.09 × 0.08
3402
5751 / 0.0786
5751/51/197
1.071
2093 / 0.0817
2093/102/208
1.343
R1 b = 0.0371, wR2 c = 0.0673
R1 b = 0.1216, wR2 c = 0.3268
2.63 / -1.07
Largest diff. peak / hole / e Å-3
Flack parameter
0.38 / -0.73
0.001(14)
2
a Goodness–of–fit = [Σ (w (Fo – Fc2)2] / (Nobsvns – Nparams)]1/2, based on all data;
b R1 = Σ ( |Fo| – |Fc| ) / Σ |Fo|;
2
2 2
c wR2 = [Σ[w (Fo – Fc2)2] / Σ[w (Fo ) ]]1/2.

27
Table II: Some selected bond lengths (Å) and angles (deg) for complexes Pd3c and Pd2d
Pd3c
Pd2d*
Pd–Cl(1)
2.3329(12)
2.2913(12)
2.033(2)
2.033(2)
1.287(3)
1.502(4)
1.452(5)
1.346(4)
1.441(5)
1.516(5)
1.364(4)
1.310(5)
1.342(4)
1.343(4)
1.356(5)
180.00(15)
93.38(7)
86.62(7)
173.24(15)
116.1(3)
106.6(3)
105.6(3)
108.2(3)
107.6(3)
108.6(3)
109.6(3)
108.6(3)
Pd–Cl(1)
Pd–Cl(2)
Pd–N(1)
Pd–N(2)
N(1)–C(1)
2.288(6)
2.270(5)
2.033(16)
2.006(17)
1.32(3)
Pd–Cl(2)
Pd–N(1)
Pd–N(1A)a
N(1)–C(1)
N(1)–C(3)
C(1)–C(8)
C(1)–C(7)
1.39(3)
C(1)–O(1)
O(1)–C(2)
C(2)–C(3)
C(8)–N(2)
C(7)–N(2)
N(2)–N(3)
1.38(3)
1.28(3)
N(2)–N(3)
N(3)–N(4)
N(4)–C(9)
C(9)–C(8)
Cl(2)–Pd–Cl(1)
N(1)–Pd–Cl(1)
N(1)–Pd–Cl(2)
N(1)–Pd–N(1A)a
N(1)–C(1)–O(1)
C(1)–O(1)–C(2)
O(1)–C(2)–C(3)
C(3)–N(1)–C(1)
C(8)–N(2)–N(3)
N(2)–N(3)–N(4)
N(3)–N(4)–C(9)
C(9)–C(8)–N(2)
Cl(2)–Pd–Cl(1)
N(1)–Pd–Cl(1)
N(1)–Pd–N(2)
N(2)–Pd–Cl(2)
N(1)–C(1)–C(7)
90.3(2)
174.0(5)
80.2(6)
175.2(5)
121.2(17)
C(7)–N(2)–N(3)
107.5(18)
*Data for complex Pd2d only preliminary; a at +y, +x. 1–z;

28
Captions for Figures
Figure 1. DFT-optimized structures of Pd1a and Pd1c (C-PCM/B97X calculations, acetonitrile
as continuous medium). Color map: hydrogen, white; carbon, grey; nitrogen, blue;
oxygen, red; palladium, green. Selected computed bond lengths for Pd1a (Å): Pd-
Callyl(trans-oxazoline) 2.110; Pd-Callyl(trans-triazole) 2.105; Pd-Callyl(central) 2.127; Pd-
N(oxazoline) 2.157; Pd-N2(triazole) 2.161. Selected computed angles for Pd1a (°):
Callyl(terminal)-Pd-Callyl(terminal)
69.6;
N2(triazole)-Pd-N(oxazoline)
77.3;
N2(triazole)-Pd-Callyl(trans-triazole) 173.2; N(oxazoline)-Pd-Callyl(trans-oxazoline)
173.0. Selected computed bond lengths for Pd1c (Å): Pd-Callyl(trans-oxazoline) 2.106;
Pd-Callyl(trans-triazole) 2.108; Pd-Callyl(central) 2.124; Pd-N(oxazoline) 2.182; Pd-
N2(triazole) 2.157. Selected computed angles for Pd1a (°): Callyl(terminal)-Pd-
Callyl(terminal) 69.4; N2(triazole)-Pd-N(oxazoline) 77.4; N2(triazole)-Pd-Callyl(trans-
triazole) 174.8; N(oxazoline)-Pd-Callyl(trans-oxazoline) 176.0.
Figure 2 ORTEP drawing of Pd2d, showing also the numbering scheme. Thermal ellipsoids are
at the 40% probability level. Hydrogen atoms are omitted for clarity; alternate positions
of disordered atoms are drawn with dashed bonds.
Figure 3. ORTEP drawing of Pd3c, showing also the numbering scheme. Thermal ellipsoids are
at the 40% probability level. Hydrogen atoms are omitted for clarity; alternate positions
of disordered atoms are drawn with dashed bonds.
Figure 4. DFT-optimized structures of Pd3a and Pd3c (C-PCM/B97X calculations, acetonitrile
as continuous medium), with H---Cl (3,-1) b.c.p. and related interbasin surface.  =
electron density, V = potential energy density, E = electron density, 2  = Laplacian of
electron density. All quantities in a.u. Color map: hydrogen, white; carbon, dark yellow;
nitrogen, blue; oxygen, red; chlorine, green; palladium, pink. Cartesian coordinates are
collected in a separated file.

29
FIGURE 1