Efficient Mizoroki–Heck coupling reactions using phosphine-modified Pd(II)–picolinate complex

Article abstract of DOI:10.1080/00397911.2018.1428347

Efficient Mizoroki–Heck couplings were obtained using a very easily synthesizable palladium(II) complex of hemilabile N–O ligand (picolinate), with high turnover frequencies up to >10,000 h^?1, in just 15 min, with high selectivity of >99% to the desired products. Wide applicability of the simple-looking palladium complex catalyst was established with differently functionalized substrates. Catalyst screening studies revealed intricate details of dependence of catalyst performance on different reaction parameters and conditions and arriving at the optimized facile methodology.

Full text of DOI:10.1080/00397911.2018.1428347

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
Efficient Mizoroki–Heck coupling reactions using
phosphine-modified Pd(II)–picolinate complex
Sonam Sharma & Bibhas R. Sarkar
To cite this article: Sonam Sharma & Bibhas R. Sarkar (2018): Efficient Mizoroki–Heck coupling
reactions using phosphine-modified Pd(II)–picolinate complex, Synthetic Communications, DOI:
10.1080/00397911.2018.1428347
To link to this article: https://doi.org/10.1080/00397911.2018.1428347
View supplementary material
Published online: 09 Mar 2018.
Submit your article to this journal
Article views: 20
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=lsyc20

SYNTHETIC COMMUNICATIONS®
https://doi.org/10.1080/00397911.2018.1428347
Efficient Mizoroki–Heck coupling reactions using phosphine-
modified Pd(II)–picolinate complex
Sonam Sharma and Bibhas R. Sarkar
Department of Chemistry, Birla Institute of Technology and Science, Pilani, Rajasthan, India
ABSTRACT
ARTICLE HISTORY
Received 30 August 2017
Efficient Mizoroki–Heck couplings were obtained using a very easily
synthesizable palladium(II) complex of hemilabile N–O ligand
−
1
KEYWORDS
(picolinate), with high turnover frequencies up to >10,000 h , in just
15 min, with high selectivity of >99% to the desired products. Wide
Heck coupling; hemilabile
N–O ligand; homogeneous
catalysts; Pd(II)-complex;
picolinate
applicability of the simple-looking palladium complex catalyst was
established with differently functionalized substrates. Catalyst
screening studies revealed intricate details of dependence of catalyst
performance on different reaction parameters and conditions and
arriving at the optimized facile methodology.
GRAPHICAL ABSTRACT
Introduction
Palladium catalysts have been known for high performance in different types of C–C
coupling reactions such as Mizoroki–Heck, etc., used in synthesis chemistry for natural
product and pharmaceutical intermediates, polymer building units, specialty chemicals
and pesticide building blocks, etc., and hence have gained importance in the last few
[
1]
decades. Typically during a Mizoroki–Heck-type C–C coupling, the reaction between
an organic halide and alkene, role of the Pd-complex, is considered prime important in
catalyst performance in terms of activity and selectivity. In addition, some important
CONTACT Bibhas R. Sarkar
bibhas.sarkar@pilani.bits-pilani.ac.in
Department of Chemistry, Birla Institute of
Technology and Science, Pilani Campus, Vidya Vihar, Rajasthan 333031, India.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lsyc.
Supplemental data (synthesis and characterization of all the reaction products [ H and C NMR traces]) can be accessed
on the publisher’s website.
1
13
©
2018 Taylor & Francis

2
S. SHARMA AND B. R. SARKAR
aspects like facile ligand synthesis and cost pertaining to that, and the stability of the metal
complex, sensitivity to air/oxygen/aqueous environment, contribute greatly to overall
economic viability of a metal complex catalyst for large-scale applications.[2] Developmen-
tal approaches have been reported such as design of novel ligands/Pd-complexes having
myriad of donor centers (C, N, O, P, S, etc.), ligand denticity (mono-, bi-, polydentate,
etc.), use of different media to assist catalyst–product separation, etc. with varied shares
of advantages and drawbacks in their syntheses and applications. Majority of the high-
efficiency catalysts with ingenious phosphine-derived ligands reported are associated with
multistep ligand-synthesis processes (including stoichiometric steps), and hence expensive
mostly, have enhanced sensitivity to moisture and air, thus diminishing the chance of
industrial viability.[3] Among the other classes of ligands, phosphine-free ligands, typically
[
4]
functionalized N-heterocyclic carbenes/N-donor ligands were reported.
Another
important class of compounds named as Schiff’s bases have also been used extensively
for catalyzing different kinds of reactions. In a very recent report, complexes of different
Schiff’s base type N–O ligands were studied for Heck coupling reactions with promising
results. In the same context, Pd-complexes of hemilabile N–O ligands might also play
important roles in Mizoroki–Heck catalysis. In another report, new N–O ligand was
reported for Pd-catalyzed Mizoroki–Heck coupling in water presenting good promise
but with low TOF (<10 h ). As exemplified by Guo et al., Pd-complexes of these
ligands were found to have moderate to high activity under phosphine-free conditions.
Phosphine-free bispicolinate complex of palladium has also been reported by Iyer et al.
[
5]
[
6]
−
1
[7]
[8]
[
9]
for the Heck reactions, but with moderate performance only. However, Pd-complexes
of simple hemilabile N–O ligands such as picolinate along with another phosphine ligand
have been found to catalyze hydroxycarbonylation reactions and Suzuki cross-coupling
[
10]
reactions with high efficiency and stability.
We herein report the use of phosphine-
containing Pd–picolinate complex as efficient catalyst for Heck coupling reactions having
high to excellent performance.
Phosphine-containing palladium picolinate complex [Pd–Pyca complex] was obtained
[
10(a)]
by synthesis process as described elsewhere.
The complex was obtained as pale yellow
powder and was used for the Mizoroki–Heck coupling reactions after proper purification
and characterization which matched with the data in literature.
[
(10a)]
The reaction of
iodobenzene with styrene was considered as model reaction for optimization of catalyst
performance as shown in Scheme 1.
Table 1 contains the details of optimization of reaction parameters with respect to the
solvent used, base, temperature. It was observed that the catalyst showed good performance
with a relative ratio of 1:1.2 at 100 °C.
The conversion, selectivity (and hence GC yields) were calculated on the basis of
quantification by a calibrated gas chromatographic technique. The selectivity in all the
Scheme 1. Mizoroki-Heck coupling of iodobenzene with styrene using palladium(II) picolinate complex.

SYNTHETIC COMMUNICATIONS®
3
a
Table 1. Optimization of reaction conditions.
b
Entry
Solvent
Base
Temperature (°C)
Time (min)
Yield, %
1
2
3
4
5
6
7
8
9
MeOH
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
70
100
100
80
65
60
60
70
30
60
40
30
50
40
60
30
60
40
15
15
35.7
40
Toluene
Dioxane
EtOH
45
44
3
CH CN
80
50
Neat
DMSO
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
80
20
100
100
100
100
100
100
100
80
69
90.1
72
K
2
CO
Cs CO
Et
NaHCO
Na CO
3
10
11
12
13
14
15
16
2
3
75
3
N
30
3
58
2
3
65.2
80
NaOAc
NaOAc
NaOAc
120
130
99.8
99.8
a
b
Reaction conditions: Iodobenzene: 1.0 mmol, Styrene: 1.2 mmol, Base: 1.5 mmol, Pd-catalyst: 0.007 mmol, Solvent: 3 mL,
GC Yield.
cases was found to be >99% toward the desired product only using this catalyst indicating a
highly selective catalyst. Among the different solvents tested (Table 1, entries 1–7),
dimethyl formamide (DMF) showed good conversions initially (90.1%). Almost all the
solvents tested gave satisfactory conversions in the range of ∼30–90% within very short
reaction times indicating high catalyst efficiency. As we know, the catalytic performance
is also dependent on the base used, we tested different bases to choose the best one (Table 1,
entries 8–13). Optimization of the bases revealed that sodium acetate, NaOAc, was the
most efficient one. Once the base and the solvent were fixed, the reaction was optimized
with respect to the reaction temperature and 120 °C was considered as optimized among
8
0, 100, 120, and 130 °C, respectively (Table 1, entries 8, 14–16).
It was observed that the catalyst performance was enhanced with temperature from
∼
80% conversion at 80 °C till about 120 °C with ∼99.8% conversion in just 0.25 h. On
further rise to 130 °C, the catalyst performance did not change anyway. The optimized
reaction conditions thus obtained were used for subsequent studies. The typical
concentration–time profile of the optimized reaction of styrene and iodobenzene is
presented in Figure 1, which shows the almost complete conversion of the limiting reagent,
i.e., iodobenzene and no other side products other than the desired product stilbene.
To understand the efficiency of developed catalyst, another quantitative aspect of the
−1
catalytic reaction namely turnover frequency (TOF, h ) was used, which integrated the
time required for the reactions and hence can be an indicator of the catalytic activity. With
the understanding of the optimized reaction conditions, we wanted to explore the
maximum efficiency boundary with respect to the catalyst performance (activity and
selectivity). We varied the substrate-to-catalyst (S/C) ratio gradually within the workable
handling limits, with slight increase in every step to obtain the activities (in TOF) for
comparison and subsequent further increment. The results are tabulated in Table 2.
It was clearly observed that the Pd–pyca complex catalyst has a very high activity for
−1
Mizoroki–Heck coupling reaction with the highest observed TOF of 10,715 h and may
be considered as an efficient homogeneous Pd-complex catalyst with hemilabile N–O
ligand for Mizoroki–Heck coupling reactions. The high TOF of the catalyst was mostly
observed for the bromoarenes and iodoarenes, but we could not get impressive results

4
S. SHARMA AND B. R. SARKAR
Figure 1. Concentration–time profile for optimized catalytic reaction.
for the Heck coupling involving chloroarenes (∼36% conversion with chlorobenzene, entry
2
0, Table 3), and the scope of such experimentation is open. Having found this high
activity for the coupling reactions, we wanted to demonstrate the applicability of the
catalyst to various substituted substrates having a variety of functional groups as presented
in Table 3. The study of the scope of application to various derivatives showed impressive
results with majority of reactions showing more than 95% conversion within a very short
reaction time of 15 min. The electron-donating groups as well as the electron-withdrawing
substituents on the aryl ring showed almost comparable performance in the catalytic Heck
couplings. The standard reaction had also been conducted (Table 3, Entry 21) in
gram-scale to visualize larger scale application. It may be noted that the Pd–pyca complex
outperforms the activity shown by the catalyst precursors alone, e.g., Pd(OAc) alone
2
(
∼31% conversion in 30 min) and Pd(OAc) /PPh (∼43% conversion in 30 min), and
2
3
hence the role of picolinate ligand was observed to be vital in the performance of the
Pd-catalyst for Mizoroki–Heck reactions.
The comparative study of the activity of present catalyst with the reported catalyst systems
reveals that this work is a significant advancement in terms of use of an easily available cheap
picolinate ligand in the Pd-complex, over the expensive ligands requiring multistep syntheses.
Comparing the different catalyst systems described in the Bi- and multidentate P- or N-based
[2e]
ligands for the Mizoroki–Heck reactions in the review by Farina, it can be stated that the
majority of the reported catalysts work at 130–150 °C, showing very high TONs, but take
a
Table 2. Variation of substrate-to-catalyst ratio.
b
−1
Entry
Subs, mmol
Cat, mmol
Yield, %
Time, min
TOF, h
57
1
2
3
4
1
1
10
50
0.07
99
95
84
75
15
15
15
30
0.007
0.007
0.007
543
4,800
10,715
a
b
Reaction conditions: Reaction conditions: Substrates: iodobenzene, styrene in molar ratio of 1:1.2 solvent: DMF; NaOAc: 1.5
equivalents to iodobenzene, temperature: 120 °C.
GC Yield.

SYNTHETIC COMMUNICATIONS®
5
a
Table 3. Heck coupling of different aryl halide and olefins.
b
Entry
Aryl Halide
Olefin
Product
Yield, %
1
98
94
93
91
90
2
3
4
5
6
7
8
95
95
93
9
92
90
92
1
1
0
1
(Continued)

6
S. SHARMA AND B. R. SARKAR
Table 3. Continued.
b
Entry
Aryl Halide
Olefin
Product
Yield, %
99
1
2
1
3
97
99
94
1
1
4
5
1
1
1
6
7
8
96
92
93
19
99
c
2
2
0
36
92
d
1
(
1 g, 4.9 mmol)
0.81 g
a
Reaction conditions: Aryl halide: 1 mmol; alkene: 1.2 mmol; NaOAc: 1.5 mmol, Pd-catalyst: 0.007 mmol; solvent: DMF;
b
c
d
temperature: 120 °C; time: 15 min, isolated yields, time: 25 min, larger-scale reaction: iodobenzene: 4.9 mmol; styrene:
.9 mmol; NaOAc: 7.4 mmol, Pd-catalyst: 0.034 mmol, other conditions similar.
5
[
11]
>
20 h to completion, with some exceptions such as Pd/Tedicyp,
Pd/bispyridine-based
[12]
N–N ligand (higher TONs and TOFs observed than our present report). But in these cases,
the synthesis routes to such ligands are complex multistep ones compared to the picolinate

SYNTHETIC COMMUNICATIONS®
7
ligand. The Pd–picolinate–phosphine complex thus opens up scope for making economically
viable catalysts for large-scale applications, envisions potential use of the catalysts for other
types of C–C coupling reactions, and also for development of associated separable catalyst
systems.
As a conclusion, we would like to mention that the simple and facile palladium
picolinate complex has emerged as a promising catalyst for Heck coupling with high
efficiency.
Experimental details
All of the reagents and solvents are commercially available and were used as purchased
without further purification. Solvents except laboratory reagent grade were dried and
purified, when necessary. Reactions were monitored by thin-layer chromatography
(
TLC) on precoated silica gel plates from Merck (silica gel 60, F 254, 0.25 mm) using
1
00% n-hexane as mobile phase (R for trans-stilbene was 0.62). Reaction products were
f
purified by column chromatography using 100–200-mesh silica gel and eluting with
n-hexane or n-hexane/ethyl acetate mixtures. Melting points of synthesized compounds
1
13
were determined in E–Z melting point apparatus and are uncorrected. H NMR and
C
NMR spectra were recorded in Bruker-Avance II (400, 100 MHz) spectrometer and
chemical shift is given in δ units with respect to TMS as internal standard. The proton
multiplicities were mentioned as: s ¼ singlet, d ¼ doublet, t ¼ triplet, q ¼ quartet,
dd ¼ doublet of doublet, and m ¼ multiplet.
General experimental procedure for the Heck reaction
A mixture of iodobenzene (1.0 mmol), styrene (1.2 mmol), NaOAc (1.5 mmol), catalyst
(
0.007 mmol), and DMF (3 mL) was added in a round-bottom flask (no inert gas protection
was needed.). The reaction was performed at 120 °C for 15 min. Upon completion of
reaction as indicated by TLC, the reaction mixture was poured in crushed ice-water,
extracted with ethyl acetate, dried over anhydrous Na SO , concentrated in vacuum to give
2
4
crude product which was purified through column chromatography on silica gel (100–200)
to afford pure stilbenes in 90–98% yields. For GC analysis, after completion of the reaction
(indicated by TLC), a measured quantity of the reaction mixture was analyzed in a
Shimadzu 2014 GC instrument fitted with a RTX-5 column (30 m � 0.25 mm � 0.2 µm).
A calibrated method developed using known standards (starting materials, products)
was used for quantitative analysis of reaction mixtures. Conversion and TOF were
calculated as:
Moles of starting material consumed
Initial moles of starting material
Moles of starting material converted
Conversion ¼
TOF ¼
� 100
Moles of catalyst used � time
Funding
S.S. and B.R.S. acknowledge the financial supports from BITS Pilani in the forms of research fellow-
ship and Research Initiation Grant (RIG–06/03/302), respectively. Help from Prof. Satyendra Pandey
of Thapar University, India, is gratefully acknowledged.

8
S. SHARMA AND B. R. SARKAR
ORCID
Bibhas R. Sarkar
http://orcid.org/0000-0002-4386-1156
References
[
1] (a) Heck, R. F. Palladium-Catalyzed Reactions of Organic Halides with Olefins. Acc. Chem. Res.
1
979, 12, 146. DOI: 10.1002/chin.197937153; (b) Beccalli, E. M.; Broggini, G.; Martinelli, M.;
Masciocchi, N.; Sottocornola, S. New 4-Spiroannulated Tetrahydroisoquinolines by a One-
Pot Sequential Procedure. Isolation and Characterization of σ-Alkylpalladium Heck Intermedi-
ates. Org. Lett. 2006, 8, 4521; (c) Clique, B.; Fabritius, C.; Couturier, C.; Monteiro, N.; Balme, G.
Unexpected Isolation, and Structural Characterization, of a β-Hydrogen-Containing σ-Alkyl-
palladium Halide Complex in the Course of an Intramolecular Heck Reaction. Synthesis of
Polycyclic Isoquinoline Derivatives. Chem. Commun. 2003, 272. DOI: 10.1039/b211856b; (d)
Yahiaoui, S.; Fardost, A.; Trejos, A.; Larhed, M. Chelation-Mediated Palladium(II)-Catalyzed
Domino Heck−Mizoroki/Suzuki−Miyaura Reactions Using Arylboronic Acids: Increasing
Scope and Mechanistic Understanding. J. Org. Chem. 2011, 76, 2433; (e) Beletskaya, I. P.;
Cheprakov, A. V. The Heck Reaction as a Sharpening Stone of Palladium Catalysis. Chem.
Rev. 2000, 100, 3009. DOI: 10.1021/cr9903048; (f) Rostamnia, S.; Rahmani, T. Ordered
Mesoporous SBA-15/PrSO Pd and SBA-15/PrSO PdNP as Active, Reusable and Selective
3
3
Phosphine-Free Catalysts in C-X Activation Heck Coupling Process. Appl. Organometal. Chem.
015, 29, 471. DOI: 10.1002/aoc.3319.
2
[
2] (a) Guram, A. S.; Wang, X.; Bunel, E. E.; Faul, M. M.; Larsen, R. D.; Martinelli, M. J. New
Catalysts for Suzuki−Miyaura Coupling Reactions of Heteroatom-Substituted Heteroaryl
Chlorides. J. Org. Chem. 2007, 72, 5104. DOI: 10.1021/jo070341w; (b) Fleckenstein, C. A.;
Plenio, H. Aqueous Cross-Coupling: Highly Efficient Suzuki-Miyaura Coupling of
N-Heteroaryl Halides and N-Heteroarylboronic Acids. Green Chem. 2007, 9, 1287. DOI:
1
0.1039/b711965h; (c) Lindhardt, A. T.; Mantel, M. L. H.; Skrydstrup, T. Palladium-Catalyzed
Intermolecular Ene-Yne Coupling: Development of an Atom-Efficient Mizoroki-Heck-Type
Reaction. Angew. Chem., Int. Ed. 2008, 47, 2668. DOI: 10.1002/ange.200705558; (d) Wu, L.;
Li, Z.; Zhang, F.; He, Y.; Fan, Q. Air-Stable and Highly Active Dendritic Phosphine
Oxide- Stabilized Palladium Nanoparticles: Preparation, Characterization and Applications
in the Carbon-Carbon Bond Formation and Hydrogenation Reactions. Adv. Synth. Catal.
2
008, 350, 846; (e) Farina, V. High-Turnover Palladium Catalysts in Cross-Coupling and Heck
Chemistry: A Critical Overview. Adv. Synth. Catal. 2004, 346, 1553. DOI: 10.1002/
adsc.200404178; (f) Phan, N. T. S.; Van Der Sluys, M.; Jones, C. W. On the Nature of the Active
Species in Palladium Catalyzed Mizoroki-Heck and Suzuki-Miyaura Couplings - Homogeneous
or Heterogeneous Catalysis. A Critical Review. Adv. Synth. Catal. 2006, 348, 609. DOI: 10.1002/
adsc.200505473.
[
[
3] (a) Billingsley, K.; Buchwald, S. L. Highly Efficient Monophosphine-Based Catalyst for the
Palladium-Catalyzed Suzuki−Miyaura Reaction of Heteroaryl Halides and Heteroaryl Boronic
Acids and Esters. J. Am. Chem. Soc. 2007, 129, 3358. DOI: 10.1002/chin.200730073; (b)
Lipshutz, B. H.; Taft, B. R. Heck Couplings at Room Temperature in Nanometer Aqueous
Micelles. Org. Lett. 2008, 10, 1329. DOI: 10.1021/ol702755g.
4] Kantchev, E. A. B.; O’Brien, C. J.; Organ, M. G. Palladium Complexes of N-Heterocyclic
Carbenes as Catalysts for Cross-Coupling Reactions—A Synthetic Chemist’s Perspective.
Angew. Chem. Int. Ed. 2007, 16, 2768. DOI: 10.1002/chin.200728241.
[
5] Jain, V. K.; Jain, L. The Chemistry of Binuclear Palladium(II) and Platinum(II) Complexes.
Coord. Chem. Rev. 2005, 249, 3075–3197. DOI: 10.1016/j.ccr.2005.06.020.
[
6] Andrade, A. P. S.; Arantes, L. M.; Kadooca, J. Y.; Carvalho, R. L.; de Fa´tima, A.; Sabino, A. A.
Palladium Complexes with Tetradentate Schiff Bases or their Corresponding Amines:
Synthesis and Application in Heck Reactions. ChemistrySelect. 2016, 5, 886. DOI: 10.1002/
slct.201600244.

SYNTHETIC COMMUNICATIONS®
9
[
[
[
7] Wanga, Y.; Yang, Q.; Yang, L.; Shi, J.; Zhang, M. A Novel N–O Ligand for Palladium-Catalyzed
Mizoroki–Heck Reaction in Neat Water. Tetrahedron Lett. 2013, 54, 5314–5317. DOI: 10.1016/
j.tetlet.2013.07.097.
8] Cui, X.; Li, J.; Zhang, Z-P.; Fu, Y.; Liu, L.; Guo, Q-X. Pd(quinoline-8-carboxylate)2 as a
Low-Priced, Phosphine-Free Catalyst for Heck and Suzuki Reactions. J. Org. Chem. 2007, 72,
9
342–9345.
9] Iyer, S.; Kulkarni G. M.; Ramesh, C. Mizoroki – Heck Reaction, Catalysis by Nitrogen Ligand
Pd Complexes and Activation of Aryl Bromides. Tetrahedron 2004, 60, 2163–2172.
[
10] (a) Jayasree, S.; Seayad, A.; Chaudhari, R. V. Novel Palladium(II) Complex Containing a
Chelating Anionic N−O Ligand: Efficient Carbonylation Catalyst. Org. Lett. 2000, 2(2),
2
03–206; (b) Sarkar, B. R.; Chaudhari, R. V. Ossification: A New Approach to Immobilize
Metal Complex Catalysts—Applications to Carbonylation and Suzuki Coupling Reactions.
J. Catal. 2006, 242(1), 231–238. DOI: 10.1016/j.jcat.2006.05.032.
[
[
11] Feuerstein, M.; Doucet, H.; Santelli, M. Efficient Heck Vinylation of Aryl Halides Catalyzed by
a New Air-Stable Palladium-Tetraphosphine Complex. J. Org. Chem. 2001, 66, 5923.
DOI: 10.1021/jo015645b.
12] Najera, C.; Gil-Molto, J.; Karlstro, S.; Falvello, L. R. Di-2-Pyridylmethylamine-Based Palladium
Complexes as New Catalysts for Heck, Suzuki, and Sonogashira Reactions in Organic and
Aqueous Solvents. Org. Lett. 2003, 5(9), 1451.