New palladium-bis(oxazoline)-phosphine complexes: Synthesis, characterization and catalytic application in alkoxycarbonylation of alkynes

Article abstract of DOI:10.1080/00958972.2016.1163688

New cationic palladium-bis(oxazoline)-phosphine (Pd-BOX-PR₃) complexes (Pd-BOX-B and Pd-BOX-C) have been synthesized and characterized using ¹H, ¹³C and ³¹P NMR, FTIR spectroscopy, and electrospray ionization mass spectrometry (ESI-MS). The new complexes were used as catalysts in the alkoxycarbonylation of alkynes with various alcohols as nucleophiles. The carbonylation has produced the gem-α,β-unsaturated ester isomer (3) in high regioselectivity and excellent yields. The catalyst systems have been optimized by screening the type of palladium complexes and also by varying the reaction parameters including the reaction time, solvent, and temperature. A mechanism of the catalytic cycle based on a N-protonated palladium bis(oxazoline) phosphine active species was proposed for the alkoxycarbonylation reaction. (Figure Presented.).

Full text of DOI:10.1080/00958972.2016.1163688

Journal of Coordination Chemistry
ISSN: 0095-8972 (Print) 1029-0389 (Online) Journal homepage: http://www.tandfonline.com/loi/gcoo20
New palladium-bis(oxazoline)-phosphine
complexes: synthesis, characterization and
catalytic application in alkoxycarbonylation of
alkynes
Mansur B. Ibrahim, Rami Suleiman & Bassam El Ali
To cite this article: Mansur B. Ibrahim, Rami Suleiman & Bassam El Ali (2016): New
palladium-bis(oxazoline)-phosphine complexes: synthesis, characterization and catalytic
application in alkoxycarbonylation of alkynes, Journal of Coordination Chemistry, DOI:
10.1080/00958972.2016.1163688
To link to this article: http://dx.doi.org/10.1080/00958972.2016.1163688
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Mar 2016.
Published online: 07 Apr 2016.
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Date: 08 April 2016, At: 07:32

Journal of Coordination Chemistry, 2016
http://dx.doi.org/10.1080/00958972.2016.1163688
New palladium-bis(oxazoline)-phosphine complexes: synthesis,
characterization and catalytic application in alkoxycarbonylation
of alkynes
Mansur B. Ibrahima, Rami Suleimanb and Bassam El Alia
b
aChemistry department, King fahd university of Petroleum & minerals, dhahran, saudi arabia; Center of research
excellence in Corrosion, King fahd university of Petroleum & minerals, dhahran, saudi arabia
ARTICLE HISTORY
ABSTRACT
received 8 october 2015
accepted 18 february 2016
New cationic palladium-bis(oxazoline)-phosphine (Pd-BOX-PR3) complexes
(Pd-BOX-B and Pd-BOX-C) have been synthesized and characterized using
1H, 13C and 31P NMR, FTIR spectroscopy, and electrospray ionization mass
spectrometry (ESI-MS). The new complexes were used as catalysts in the
alkoxycarbonylation of alkynes with various alcohols as nucleophiles. The
carbonylation has produced the gem-α,β-unsaturated ester isomer (3) in
high regioselectivity and excellent yields. The catalyst systems have been
optimized by screening the type of palladium complexes and also by
varying the reaction parameters including the reaction time, solvent, and
temperature. A mechanism of the catalytic cycle based on a N-protonated
palladium bis(oxazoline) phosphine active species was proposed for the
alkoxycarbonylation reaction.
KEYWORDS
Palladium; bis(oxazoline);
alkoxycarbonylation; activity;
selectivity
+ ClO4-
O
O
N
N
Pd
Cl PPh3
OR'
R
H
+
CO (100 psi) + R'OH
R
p-TsOH, CH3CN
R=Aryl, Alkyl
110 oC, 1 h
O
Selectivity > 97%
1. Introduction
Palladium-catalyzed carbonylation of alkynes in the presence of alcohol or amine as a nucleophile
represents a major industrial process for the production of value-added bulk and fine chemicals. It is a
versatile synthetic pathway to a wide range of linear, branched and cyclic α,β-unsaturated carboxylic
acids, amides and their derivatives in one step and from easily accessible starting materials [1–5]. The
carboxamides and cinnamate esters produced from the above reactions are used as building blocks
for various materials ranging from polymers [6], light-sensitive, and electrically conductive materials,
detergents, flavors, fragrances, and various pharmaceuticals [7].
CONTACT Bassam el ali
belali@kfupm.edu.sa
© 2016 informa uK limited, trading as taylor & francis Group

2
M. B. IBRAHIM ET Al.
A highly active and selective catalyst is necessary for a successful carbonylation reaction. Palladium
complexes are the most efficient catalysts for alkoxycarbonylation reactions, attributed to their high
activity under mild conditions. Most of the catalytic systems used in carbonylation reactions are gener-
ated in situ from a palladium salt, a phosphine ligand, and a weakly coordinating acid [3, 8, 9]. Various
catalytic systems [10–12] have been used in the carbonylation of alkynes at low CO pressure. However,
many systems are associated with relatively low activity and often give a mixture of products.
As continuation of our interest in exploring the synthesis, structural chemistry, and catalytic activity
of palladium-bis(oxazoline) complexes [13–15], we report in this paper the synthesis, characterization,
and catalytic activity of new palladium-bis(oxazoline)-phosphine (Pd-BOX-PR3) complexes. Although
a number of mixed ligand complexes of nitrogen and phosphine donors have been reported [16–19],
the presence of the BOX as a chelating nitrogen ligand added more stability and catalytic activity to
the complexes as demonstrated in our previous studies in coupling reactions [13–15]. The presence
of phosphine was mandatory for the carbonylation reactions. The complexes described in this paper
are the first examples of cationic mixed ligand palladium complexes having both bis(oxazoline) and
phosphine. Palladium bis(oxazoline) complexes are rarely studied as catalysts in carbonylation reactions
[20]. This encouraged us also to investigate the catalytic activity of our newly synthesized palladium
complexes in the alkoxycarbonylation of various alkynes. The catalyst systems have been optimized
by screening the types of phosphine ligand and also by varying the reaction parameters including the
reaction time, solvent, and temperature.
2. Experimental
2.1. Materials
Materials for the synthesis of ligands and complexes were purchased from Sigma–Aldrich Company
and used as received. All solvents (reagent grade) used in the synthesis were distilled and dried before
use. The products were purified using flash column chromatography packed with Silica gel 170–400
Mesh, Fisher chemical (Fisher Scientific, US). Merck 60 F254 silica gel plates (250 μm layer thickness) were
used for thin layer chromatography (TlC).
2.2. Instrumentation
1H, 13C, and 31P NMR spectral data were obtained using 500 MHz NMR (Jeol 1500 model). Chemical shifts
were recorded in ppm using tetramethylsilane (TMS) as reference for 1H and 13C spectra and phosphoric
acid as reference for 31P spectrum. CD2Cl2 was used as NMR solvent. IR spectra were recorded in wav-
enumbers (cm−1) using a FTIR spectrometer (Perkin-Elmer 16F model). A Varian Saturn 2000 GC-MS
machine equipped with a 30 m capillary column was used to analyze the products. Agilent 6890 Gas
chromatograph (GC) was used to monitor the reactions and analyze the products. Molecular weight
analyses of the complexes were performed on an lTQ-Orbitrap mass spectrometer (Thermo Scientific,
San Jose, CA, USA) equipped with a HESI-II electrospray source (ESI-MS) using a metal spray needle.
2.3. Synthesis of palladium-bis(oxazoline) complex (Pd-BOX-A) [13]
A solution of bis(oxazoline) ligand A (0.5 mmol) and bis(benzonitrile) palladium(II) chloride (0.5 mmol)
in dried DMF (8.0 ml) was stirred at room temperature for 6 h. The solvent was removed under reduced
pressure using a rotary evaporator. The crude product was then dissolved in dichoromethane at room
temperature and layered with hexane. The product was obtained as needles. These pure crystals were
separated, washed with diethyl ether, dried under vacuum, and characterized using different spectro-
scopic techniques including 1H and 13C NMR, elemental analysis, IR spectroscopy, and X-ray diffraction
analysis.

JOURNAl OF COORDINATION CHEMISTRy
3
2.3.1. 2,2′-(1,2-phenylene)bis(4,4-di-methyl-4,5-dihydrooxazole)-N,N′-dichloridopalladium(II)
(Pd-BOX-A)
Pale yellow needle shape crystals; yield (81%); m.p. (252 °C), 1H NMR (500 MHz, DMSO) δ (ppm): 7.95 (m,
4H, CH-3,4,5,6 arom), 4.39 (s, 4H, OCH2×2), 1.52 (s, 6H, NC(CH3)2), 1.57 (s, 6H, NC(CH3)2, 13C NMR (125 MHz,
CDCl3) δ (ppm); 27.8 (NC(CH3)×4), 70.8 (NC), 80.5 (OCH2), 125.5 (C-1,2 arom), 129.5 (C-3,4 arom), 132.9
(C-5,6 arom), 163.9.(OCN); IR (KBr) (vcm−1): 2968, 1632, 1260, 1193. Anal. Calcd for C16H20Cl2N2O2Pd
(449.67): C, 42.74; H, 4.48; N, 6.23. Found: C, 42.71; H, 4.46; N, 6.29%.
2.4. Synthesis of palladium-bis(oxazoline)-phosphine complexes
To a stirred solution of Pd-BOX-A (0.25 mmol) in 10 ml dichloromethane, a stoichiometric amount of
phosphine (0.25 mmol) (dissolved in 2 ml of dichloromethane) was added. The resulting mixture was
stirred for 30 min at room temperature. Subsequently, the solvent was removed using a rotary evap-
orator at reduced pressure. The resulting solid product was dissolved in DMF (5 ml). A stoichiometric
amount (0.25 mmol) of silver perchlorate (AgClO4) was added and the mixture was stirred in the dark
for 30 min. After complete reaction, the mixture was filtered to remove the AgCl precipitate. The solvent
was removed under reduced pressure to give the appropriate mixed ligand palladium complex. The
product was dissolved in dichloromethane and layered with n-hexane in an attempt to obtain pure
microcrystals. The products were characterized using various spectroscopic and analytical techniques
and the molecular weights were established on the basis of ESI-MS analyses.
2.4.1. Chlorido (2,2′-(1,2-phenylene)bis(4,4′-dimethyl-4,5-dihydrooxazole)-N,N′)
triphenylphosphino palladium(II) perchlorate (Pd-BOX-B)
1
yellow solid; yield: 72%; m.p. 230 °C; H NMR (500 MHz, CD2Cl2) δ (ppm): 8.11 (d, J = 7.6 Hz, 1H, CH
arom), 8.00 (m, J = 5.2 Hz, 1H, CH arom), 7.81 (d, J = 3.05 Hz, 2H, CH arom), 7.56 (m, 3H, CH arom), 7.46
(m, 12H, CH arom), 4.51 (d, J = 8.85 Hz, 1H, OCH), 4.40 (d, J = 8.85 Hz, 1H, OCH), 4.33 (d, J = 8.85 Hz, 1H,
OCH), 3.49 (d, J = 8.85 1H, OCH), 1.73 (s, 3H, NCCH3), 1.66 (s, 3H, NCCH3), 1.49 (s, 3H, NCCH3), 0.73 (s, 3H,
NCCH3); 13C NMR (125 MHz, CD2Cl2) δ (ppm): 24.35 (NCCH3), 27.81 (NCCH3), 29.46 (NCCH3), 31.20 (NCCH3),
71.47 (NC), 72.66 (NC), 81.25 (OCH2), 82.44 (OCH2), 125.37, 127.53, 128.54, 129.16, 130.08, 131.11, 132.46,
132.48, 133.47, 134.28, 134.70, 165.98, 166. 31P NMR (500 MHz, CD2Cl2) δ (ppm); 21.34 (PPh3); IR (KBr)
(vcm−1): 3043, 2974, 2914, 2356, 1626, 1442, 1373, 1324, 1093, 949, 750, 701, 622, 527; ESI-MS: 676.12;
Anal. Calcd for C34H35Cl2N2O6PPd (775.95): C, 52.63; H, 4.55; N, 3.61. Found: C, 52.41; H, 4.49; N, 3.60%.
2.4.2. Chlorido(2,2′-(1,2-phenylene)bis(4,4′-dimethyl-4,5-dihydrooxazole)-N,N′)tris(p-methoxy
phenylphosphino) palladium(II) perchlorate (Pd-BOX-C)
1
yellow solid, yield: 69%; m.p. 215 °C; H NMR (500 MHz, CD2Cl2) δ (ppm): 8.08 (d, J = 7.9 Hz, 1H, CH
arom), 7.97 (m, 1H, CH arom), 7.82 (d, J = 3.7 Hz, 2H, CH arom), 7.35 (m, 6H, CH arom), 6.91 (m, 6H, CH
arom), 4.48 (d, J = 8.6 Hz,1H, OCH), 4.39 (d, J = 8.8 Hz, 1H, OCH), 4.30 (d, J = 8.6 Hz, 1H, OCH), 3.84 (s, 9H,
OCH3), 3.56 (d, J = 9.2 Hz, 1H, OCH), 1.73 (s, 3H, NCCH3), 1.65 (s, 3H, NCCH3), 1.48 (s, 3H, NCCH3), 0.81 (s,
3H, NCCH3), 13C NMR (125 MHz, CD2Cl2) δ (ppm); 24.37 (NCCH3), 27.74 (NCCH3), 29.40 (NCCH3), 30.98
(NCCH3), 55.98 (OCH3), 71.42 (NC), 80.90 (OCH2), 82.29 (OCH2), 114.61, 114.71, 114.84, 120.23, 130.13,
131.05, 133.41, 134.16, 136.20, 136.30, 136.42, 162.76, 162.96; 31P NMR (500 MHz, CD2Cl2) δ (ppm); 18.87
[(p-MeO-C6H4)3P]; IR (KBr) (vcm−1) 3062, 2973, 2840, 1897, 1634, 1592, 1567, 1500, 1458, 1407, 1373, 1292,
1260, 1180, 1096, 1020, 942, 828, 800, 717, 623, 541; ESI-MS: 765.15; Anal. Calcd for C37H42Cl2N2O9PPd
(867.03): C, 51.25; H, 4.88; N, 3.23. Found: C, 51.42; H, 4.76; N, 3.40%.
2.5. General procedure for the alkoxycarbonylation of alkynes
A stainless steel autoclave equipped with a glass liner, gas inlet valve, and pressure gage was used for the
alkoxycarbonylation reaction. Pd-BOX-PR3 (0.02 mmol) dissolved in 2 mlacetonitrile, p-toluenesulfonic acid

4
M. B. IBRAHIM ET Al.
(p-TsOH) (0.30 mmol), alkyne (2.0 mmol), and alcohol (8.0 mmol) were added to the glass liner. Additional
acetonitrile (8 ml) was added to the mixture in the glass liner. The glass liner was then placed in the 45 ml
autoclave. The autoclave was vented three times with carbon monoxide and then pressurized to 100 psi of
CO.The mixture was heated to 110 °C and maintained at this temperature under stirring for the required time.
After complete reaction, the mixture was cooled to room temperature and excess CO was released in a fume
hood.The mixture was filtered and the filtrate was immediately analyzed with GC and GC-MS [7].The spectral
data of the α,β-unsaturated esters prepared in this study were in agreement with those reported [21–24].
3. Results and discussion
3.1. Synthesis of BOX ligand, Pd-bis(oxazoline) dichloro (Pd-BOX-A) and Pd-bis(oxazoline)-
chloro phosphine (Pd-BOX-B and Pd-BOX-C) complexes
The BOX ligand and Pd-BOX-A complex were prepared following the method reported [13] (scheme 1).
1
Pd-BOX-B and Pd-BOX-C were obtained by introducing the appropriate phosphine to Pd-BOX-A. H
and 13C NMR chemical shifts for both the BOX ligand and Pd-BOX-A were consistent with the reported
structure. The BOX ligand is a symmetrical molecule, hence the two oxazoline moieties behave similarly:
a single peak was observed for the methyl protons with a chemical shift of δ 0.88 ppm, integrating
for 12 protons. The six methylenic protons are a singlet with chemical shift of δ 3.55 ppm (figure 1(a))
[12]. In the spectrum of palladium BOX complex (Pd-BOX-A), both the methyl and methylene protons
were deshielded and were observed in the downfield region due to complexation with palladium.
Unlike the spectrum of the free ligand, the two oxazoline moieties behave differently. Two singlets
were observed in the methyl region, each integrating for six protons. The methylenic protons appear
as two separate AB spin systems, with each doublet integrating for two protons (figure 1(b)) [12]. In
HO
NH2
Zn(Otf)2
+
O
C6H5-Cl, 140 oC
O
N
N
CN
CN
(2 equiv.)
BOX-A
DMF
O
N
O
O
O
Pd(PhCN)2Cl2
+
R.T., 6 h
N
N
N
Pd
Cl
Cl
Pd-BOX-A
+ ClO4
-
1. PR3, CH2Cl2
O
O
O
O
N
N
N
N
2. AgClO4, DMF
Pd
Pd
PR3
Pd-BOX-B: R=PPh3
Pd-BOX-C: R=P(p-MeO-Ph)3
Cl
Cl
Cl
Scheme 1. synthesis of BoX ligand, palladium bis(oxazoline) dichloro complex (Pd-BoX-a) and palladium bis(oxazoline) chloro
phosphine complexes (Pd-BoX-B and Pd-BoX-C).

JOURNAl OF COORDINATION CHEMISTRy
5
Figure 1. 1h nmr spectra of (a) BoX ligand, (b) Pd-BoX-a, and (c) Pd-BoX-B.
spectra of Pd-BOX-phosphine complexes (Pd-BOX-B and Pd-BOX-C), there is further splitting of both
the methyl and methylenic protons due to complete loss of symmetry in the molecules (scheme 1).
In the spectrum of Pd-BOX-B four singlets were observed in the methyl region (figure 1(c)) with each
singlet integrating for three protons. One of the four singlets is further upfield as opposed to the three
remaining singlets which resonate at nearly the same chemical shift as in Pd-BOX-A. The methylenic
protons are four different doublets integrating for one proton each (figure 1(c)). Similar to the methyl
protons, one of the four doublets is further upfield, which is probably due to the anisotropic shielding
of these protons by one of the phenyl rings of PPh3 [25]. The protons, due to the aromatic spacer of
the BOX and the aromatic phosphines, are in the aromatic region and slightly downfield as compared
to their positions in the free state. The proton NMR spectrum of Pd-BOX-C shows a similar pattern to
the spectrum of Pd-BOX-B with additional singlet at δ 3.84 ppm which was assigned to the p-methoxy
substituent.
The carbon-13 NMR spectra for the BOX ligand, Pd-BOX-A, Pd-BOX-B, and Pd-BOX-C were consistent
with the proposed structures and were in agreement with the spectra of other known BOX ligands
and Pd-BOX complexes [13–15]. For instance, in the NMR spectrum of Pd-BOX-B and Pd-BOX-C, two
sets of carbon signals were detected in the aromatic region. The weak signals represent the benzene
spacer of the BOX ligand and the intense signals represent the triphenylphosphine and p-methoxy
triphenylphosphine ligands for Pd-BOX-B and Pd-BOX-C, respectively. A downfield shift was observed
in the resonance of the imino carbon (−C=N-) in spectra of Pd-BOX-A, Pd-BOX-B, and Pd-BOX-C. This
shift is due to the increase in double bond character of the −C=N- bond as a result of coordination,
which results in its deshielding.
Similarly, in the 31P NMR spectra, the phosphorus resonances shifted from −6.0 and −11.8 ppm
in the free ligands to δ 21.3 and 18.9 ppm for Pd-BOX-B and Pd-BOX-C, respectively. These shifts are
further confirmation that the phosphine ligands are coordinated to form the mixed ligand complexes.
We recently published the crystal structure of Pd-BOX-A [13]. Attempts to grow crystals of Pd-BOX-B
and Pd-BOX-C were not successful. We considered ESI-MS as a suitable technique to establish the molec-
ular weight of our new mixed ligand complexes [26, 27]. Fortunately, the molecular weights obtained
were in agreement with the calculated molecular weights (figures 2 and 3). These results together with

6
M. B. IBRAHIM ET Al.
20150102_BM1-1 MEOH #1 RT: 0.01 AV: 1 NL: 1.06E8
T: FTMS + p ESI Full ms [100.00-2000.00]
677.11
671.17
100
95
90
85
80
75
70
65
60
55
50
45
40
35
30
25
682.12
20
15
10
5
273.16
295.14
301.08
717.19
731.21
339.13
834.17
850
778.11
800
657.15
650
255.05
250
567.29
911.29
900
201.10
200
528.08
439.07
450
381.06
400
491.06
129.05
150
937.19
950
1007.67
0
300
350
500
550
600
700
750
1000 1050
m/z
Figure 2. Proposed formulation for Pd-BoX-B based on isotope simulation and distribution is [C34h35Cln2o2PPd]+ with m/z = 676.12.
20150102_BM3-1 MEOH #51 RT: 0.38 AV:
T: FTMS + p ESI Full ms [150.00-2000.00]
1
NL: 1.35E8
767.15
100
95
90
85
80
75
70
65
60
55
50
45
40
35
30
25
20
15
789.19
273.16
10
751.13
687.18
5
295.14
459.17
383.14
400
837.23
800
220.10
200
550.54
600
1013.45
1000
1241.34 1303.15
1200 1300
1412.06
1400
1598.89
1600
1752.37
1700 1800
1916.83
1900
0
300
500
700
900
1100
m/z
1500
2000
Figure 3. Proposed formulation for Pd-BoX-C based on isotope simulation and distribution most likely is [C37h41Cln2o5PPd]+ with
m/z = 765.15.

JOURNAl OF COORDINATION CHEMISTRy
7
the information acquired from other spectroscopic techniques were used to establish the molecular
structures of the new complexes (scheme 1).
3.2. Evaluation of the catalytic activity of the newly prepared Pd-BOX complexes in the
alkoxycarbonylation of alkynes
The reaction of terminal alkynes with alcohol in the presence of carbon monoxide as carbonyl source
(alkoxycarbonylation) is a well-known methodology for the synthesis of α,β-unsaturated esters. In our
investigation, we have chosen the methoxycarbonylation of phenylacetylene (1a) using Pd-BOX as a
catalyst as a model reaction. Two α,β-unsaturated ester isomers, gem (3aa) and trans (4aa), are expected
as products from this reaction. We have studied the influence of various reaction parameters including
solvent, temperature, and type of palladium catalyst.
A preliminary alkoxycarbonylation reaction of phenylacetylene with methanol (2a) using the cat-
alyst system Pd-BOX-A/p-TsOH yielded only trace amounts of products. The in situ introduction of
triphenylphosphine as a co-ligand resulted in higher catalytic activity and improved the conversion
of phenylacetylene. This shows that the presence of a coordinated phosphine is necessary for the
alkoxycarbonylation reaction.
3.2.1. Effect of solvent
We have investigated the effect of various solvents on the catalytic activity and selectivity of the model
reaction using Pd-BOX-B/p-TsOH catalyst system. A complete conversion and excellent selectivity
towards the formation of the gem isomer 3aa were achieved with acetonitrile as a solvent (Table 1,
entry 1). The conversion of the alkyne and the selectivity in gem isomer have decreased to 43 and 75%,
respectively, when DMF was used as a solvent (Table 1, entry 2). A further decrease in the conversion of
phenylacetylene to 28% was observed with n-hexane as a solvent, with a selectivity of 90% in favor of
3aa isomer (Table 1, entry 3). Poor conversion and poor selectivity were observed when the reaction
was performed in neat methanol (Table 1, entry 5). The coordination of anions to the cationic palla-
dium center is reported to be very weak in non-polar solvents [28]. The reason for higher activity of
the alkoxycarbonylation reaction in acetonitrile is not yet understood but it is possible that this solvent
plays the dual role of solvent and a co-ligand in the catalytic cycle [7, 8].
O
Pd-BOX-B
OCH3
Ph
H
+
CO
+
CH3OH
+
Ph
OCH3
Ph
p-TsOH, Solvent
110 oC, 100 psi,1 h
(1)
O
1a
2a
4a
3a
3.2.2. Effect of temperature
After determining the best solvent for the reaction, we have studied the effect of varying the temper-
ature on the conversion and the selectivity of the methoxycarbonylation reaction of phenylacetylene
using the catalytic system Pd-BOX-B/p-TsOH/CH3CN. The catalytic activity was highly temperature
Table 1. effect of the type of solvent on the palladium-catalyzed methoxycarbonylation of phenylacetylene.a
Product distributionb (%)
Entry
Solvent
Conversionb (%)
3a
4a
1
2
3
4
5
acetonitrile
dmf
n-hexane
toluene
methanol
99
43
28
65
10
97
75
90
92
65
3
25
10
8
35
areaction conditions: Pd-BoX-B (0.020 mmol), p-tsoh (0.30 mmol), solvent (10 ml), phenylacetylene (2.0 mmol), methanol
(8.0 mmol), Co (100 psi), 110 °C, 1 h.
bdetermined by GC based on phenylacetylene.

8
M. B. IBRAHIM ET Al.
dependent. The conversion dropped significantly from 99 to 40% when the temperature was lowered
from 110 °C (Table 2, entry 5) to 60 °C (Table 2, entry 1) and decreased to 70% at 90 °C (Table 2, entry
3). The selectivity was not affected by changing the reaction temperature.
O
Pd-BOX-B
OCH3
+
Ph
H
+
CO
+
CH3OH
Ph
OCH3
Ph
p-TsOH, CH3CN
(2)
O
100 psi, 1 h
4a
2a
1a
3a
Table 2. effect of the temperature on the palladium-catalyzed methoxycarbonylation of phenylacetylene.a
Product distributionb (%)
Entry
Temperature (°C)
Conversionb (%)
3a
4a
1
2
3
4
5
60
70
90
100
110
40
58
70
90
99
95
94
98
98
97
5
6
2
2
3
areaction conditions: Pd-BoX-B (0.020 mmol), p-tsoh (0.30 mmol), acetonitrile (10 ml), phenylacetylene (2.0 mmol), methanol
(8.0 mmol), Co (100 psi), 1 h.
bdetermined by GC based on phenylacetylene.
3.2.3. Effect of the type of palladium complex
The presence of a catalyst is essential for the progress of carbonylation reactions. Palladium com-
plexes catalyze carbonylation reactions, however, the efficiency and selectivity in such reactions depend
strongly on the type of palladium precursor, the attached ligand, and other reaction parameters.
The effect of the type of palladium complex and the ligand on the methoxycarbonylation of phe-
nylacetylene was investigated. The results are summarized in Table 3. Only traces of products were
observed with Pd-BOX-A as catalyst. There was a remarkable increase in the product yield (from traces
to 75%) when triphenylphosphine was used as a co-ligand (Table 3, entries 2 and 3). The mixed ligand
palladium complexes (Pd-BOX-B and Pd-BOX-C) (Table 3, entries 4 and 5) gave full conversion with 97
and 98% selectivity, respectively, towards 3aa. To highlight more the activity of our newly prepared
complexes, we have compared them with commercially available palladium complexes and salts such
as Pd(PPh3)2Cl2 (Table 3, entry 6) (54%), Pd(PhCN)2Cl2 (Table 3, entry 7) (traces), Pd(OAc)2 (Table 3,
entry 8) (traces), and Pd(OAc)2/PPh3 (Table 3, entry 9) (74%). The low catalytic activity or the inactivity
observed with most commercial palladium complexes and salts is an indication of the significance of
the new mixed ligand complexes on the alkoxycarbonylation reaction. The catalytic activity achieved
with the new mixed ligand complexes is higher than the activity of the individual complexes combined
(Pd-BOX-A and Pd(Ph3)2Cl2) and is a clear indication of a synergistic relationship between the donor
nitrogen and phosphorus ligands.
O
[Pd]
OCH3
+
Ph
H
+
CO
+
CH3OH
Ph
OCH3
(3)
Ph
p-TsOH, CH3CN
110 oC, 100 psi, 1 h
O
4a
2a
1a
3a

JOURNAl OF COORDINATION CHEMISTRy
9
Table 3. effect of the type of palladium catalyst on the methoxycarbonylation of phenylacetylene.a
Product distributionb (%)
Entry
Catalyst
Conversionb (%)
3a
4a
1
Pd-Box-a
traces
75
90
99
99
–
–
10
10
3
2
8
–
–
5
2c
3d
4
Pd-Box-a/PPh3
Pd-Box-a/PPh3
Pd-Box-B
90
90
97
98
92
–
5
6
7
Pd-Box-C
Pd(PPh3)2Cl2
Pd(PhCn)2Cl2
Pd(oac)2
54
traces
traces
74
8
–
95
9d
Pd(oac)2/PPh3
areaction conditions: [Pd] (0.020 mmol), p-tsoh (0.3 mmol), acetonitrile (10 ml), phenylacetylene (2.0 mmol), methanol (8.0 mmol),
Co (100 psi), 110 °C, 1 h.
bdetermined by GC based on phenylacetylene.
c0.02 mmol PPh3 was added.
d0.04 mmol PPh3 was added.
Table 4. Palladium catalyzed alkoxycarbonylation of phenylacetylene with various alcohols.a
Product distributionb (%)
Entry
Alcohol
Conversionb (%)
3aa-ag
4aa-ag
1
methanol
2a
99
97
3
2
3
4
5
6
7
ethanol
2b
Propanol
2c
Butanol
2d
isopropanol
2e
isobutanol
2f
isopentanol
2 g
99
99
99
99
99
99
98
97
96
96
97
97
2
3
4
4
3
3
areaction conditions: Pd-BoX-B (0.020 mmol), p-tsoh (0.30 mmol), acetonitrile (10 ml), phenylacetylene (2.0 mmol), alcohol
(8.0 mmol), Co (100 psi), 110 °C, 1 h.
bdetermined by GC based on phenylacetylene.
3.2.4. Effect of the type of alcohol
We have extended the scope of our study by considering various linear and branched alcohols as
nucleophiles in the alkoxycarbonylation of phenylacetylene (Table 4, entries 1–7). The activity and
selectivity were not affected by the length of the carbon chain or the presence of branching in the
alcohol nucleophile. All the reactions gave high selectivity towards the formation of the gem-α,β-un-
saturated esters 3aa-ag (equation 4).
O
Pd-BOX-B
OCH3
+
R
H
+
CO
+
CH3OH
R
OCH3
R
p-TsOH, CH3CN
110 oC, 100 psi, 1 h
(4)
O
4aa-ea
2a
1a-e
3aa-ea
3.2.5. Effect of the type of alkyne
We have further evaluated the new catalytic system in the alkoxycarbonylation of electronically different
alkynes. The palladium-bis(oxazoline)-phosphine complexes were active in the alkoxycarbonylation
reactions of various alkynes. For instance, the methoxycarbonylation of 4-ethynylanisole (1b) and 4-eth-
ynyltoluene (1c) were achieved to give excellent conversions and very high selectivity in the expected

10
M. B. IBRAHIM ET Al.
Table 5. Palladium-catalyzed methoxycarbonylation of various alkynes.a
Product distributionb (%)
Entry
Alkyne
Conversionb (%)
3aa-ea
4aa-ea
1
Phenylacetylene
99
97
3aa
98
3ba
94
3ca
95
3da
98
3
4aa
2
4ba
6
4ca
5
4da
2
1a
2
4-ethynyltoluene
98
99
79
76
1b
3
4-ethynylanisole
1c
4c
5c
4-ethynylbenzaldehyde
1d
1-decyne
1e
3ea
4ea
areaction conditions: Pd-BoX-B (0.020 mmol), p-tsoh (0.3 mmol), acetonitrile (10 ml), alkyne (2.0 mmol), methanol (8.0 mmol), Co
(100 psi), 110 °C, 1 h.
bdetermined by GC based on alkyne.
c6 h.
gem α,β-unsaturated esters 3ba and 3ca (Table 5, entries 2 and 3). Similarly, the methoxycarbonylation
of the deactivated aryl alkyne (4-ethynylbenzaldehyde) (1d) and of the alkyl alkyne (1-decyne) (1e)
were also achieved with high conversions and selectivities (Table 5, entries 4 and 5). Owing to the lower
reactivity of these unactivated alkynes, a longer reaction time was required to achieve high conversions.
3.3. Proposed mechanism of the catalytic cycle
Two reaction pathways have been proposed for palladium-catalyzed alkoxycarbonylation of alkynes:
one is based on a palladium-hydride active species (hydride cycle) [8, 28] and the other one is initiated
by a palladium-alkoxy active species (alkoxy cycle) [29]. The above two mechanisms were reported to
be the operating mechanisms for a variety of alkoxycarbonylation reactions of different unsaturated
substrates [30–32]. The formation of palladium-hydride species is commonly proposed in the presence
of acid additives [8]. However, based on the results of the screening of different reaction parameters
reported above, we propose a mechanism for our catalyst systems (scheme 2). The reaction is probably
initiated by the N-protonated palladium(0) bis(oxazoline) phosphine acetonitrile active intermediate
(1H). This intermediate is produced via reaction of Pd-BOX-B/C with p-TsOH in acetonitrile. The role of
acid as a protonating agent for nitrogen ligands has been proposed [33]. The proposition for protona-
tion to occur on nitrogen rather than the phosphorus in our catalyst system is more plausible due to
the higher reported basicity of amines compared to phosphines in acetonitrile [34]. The N-protonation
approach is more appealing to us since the experimental results inTable 3 supported the requirement of
the presence of phosphine ligand in the highly active palladium precursors in the alkoxycarbonylation of
terminal alkynes. Having a coordinated solvent attached to palladium in the active intermediate (1H) is
also expected due to the availability of solvent for this coordination. The proposed coordinating ligands
will minimize the possibility of having a palladium-hydride bond in 1H due to both steric and electronic
constraints. It is also expected that the protonation step that should lead to conversion of the bidentate
bis(oxazoline) ligand in 1H into a monodentate mode. The bidentate palladium cis-dinitrogen complexes
are regenerated later in the catalytic cycle [35, 36]. The next step involves direct proton transfer from
the protonated bis(oxazoline) to the coordinated alkyne as depicted in intermediate 2H [33]. In fact,
this step will be feasible if the nitrogen of the oxazoline ring points toward the carbon of the methylene
group of the coordinated alkyne, hence it can also explain the high regioselectivity obtained with our
catalyst system. A full computational study on the nature of the active species and the energy barrier
of proton transfer step is in progress and will be published at a later date. The resultant palladium(II)
regioselective intermediate (3H) is subjected to (i) CO addition and insertion and (ii) methanolysis of
the Pd-acyl species. The catalytic activity is independent of the type of alcohol employed as reaction
nucleophile (Table 4). This rules out the methanolysis reaction path as a termination reaction [29].

JOURNAl OF COORDINATION CHEMISTRy
11
CH3CN
O
O
O
O
N
N
N
N
Pd
Pd
PPh3
PPh3
Cl
CH3CN
H+
O
O
N
N
OMe
H
R
Pd
PPh3
CH3CN
R
H
O
O
3
1
1H
CH3CN
MeOH
O
O
O
H
N
N
N
N
Pd
+
R
Pd
H
Ph3P
CH3CN
PPh
3 R
O
5H
2H
+ PPh3
- CH3CN
O
O
O
O
O
CO
O
+
N
N
N
N
N
N
-PPh3
Pd
+
Pd
+
Pd
+
Ph3P
Ph3P
CO
R
R
R
trans isomer
(minor)
4H
3H
Scheme 2. alkoxycarbonylation of phenylacetylene by palladium bis(oxazoline) chloro phosphine complexes.
4. Conclusion
We have described the synthesis and characterization of two new palladium bis(oxazoline) phosphine
mixed ligand complexes. The molecular structures of the new complexes were proposed based on 1H,
13C and 31P NMR, FTIR, and ESI-MS data. We have also studied the activity and selectivity of the newly
synthesized mixed ligand complexes as catalysts in the alkoxycarbonylation of alkynes. The new catalytic
system showed high catalytic activity and excellent selectivity (>97%) towards the gem-α,β-unsaturated
ester isomer under mild reaction conditions and low CO pressure. Finally, a catalytic cycle based on a

12
M. B. IBRAHIM ET Al.
N-protonated palladium(0) bis(oxazoline) phosphine acetonitrile active species was proposed for our
alkoxycarbonylation catalyst system. This species protonates the alkyne to produce the two palladi-
um-vinyl key regioselective intermediates, which are subjected to further sequence of reactions that
include the CO addition and insertion, alcoholysis, and reductive elimination of products.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This project was funded by the National Plan for Science, Technology and Innovation (MARIFAH) – King Abdulaziz City for
Science andTechnology – through the Science & Technology Unit at King Fahd University of Petroleum & Minerals (KFUPM);
The Kingdom of Saudi Arabia [award number 11-PET1665-04].
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