Pincer click ligands

Article abstract of DOI:10.1002/anie.200800123

(Chemical Equation Presented) It all clicks into place: The use of "click chemistry" has been found to be highly advantageous for the selective and rapid combinatorial synthesis of a family of pincer-type ligands from relatively simple building blocks (se

Full text of DOI:10.1002/anie.200800123

Angewandte
Chemie
DOI: 10.1002/anie.200800123
Homogeneous Catalysis
Pincer Click Ligands**
Elaine M. Schuster, Mark Botoshansky, and Mark Gandelman*
Tridentate pincer-type ligands of the general form D1CD2
(where D1 and D2 are groups containing coordinating atoms)
have been used to spectacular effect in coordination, mech-
anistic, synthetic, and supramolecular chemistry, as well as in
nanoscience and in the development of sensors and molecular
switches.[1] Most significantly, the realization that pincer
ligands offer both a unique, highly protective environment
for the coordinated metal center and opportunities to fine-
tune the steric and electronic properties of the metal atom has
generated extensive research into the use of these complexes
as catalysts.[2] As a result, many important and challenging
catalytic processes based on such systems have been devel-
oped. It is generally accepted that the reactivity, selectivity,
and catalytic performance of pincer-based systems rely to a
great extent on the characteristics of the donor groups D in
the carefully selected ligand. The optimization of tailor-made
catalysts involves extensive experimental investigation, in
which the laborious synthesis of the ligands is often a serious
bottleneck. In particular, the synthesis of nonsymmetrically
substituted D1CD2 ligands (D1 and D2 are different groups)
represents a considerable challenge, as their preparation
usually includes a series of steps and separations that
commonly result in low yields.[3]
Consequently, the development of efficient and powerful
methods for the rapid synthesis of a wide variety of tailor-
made ligands is of high importance. Although several
methods for the preparation of bidentate ligand libraries
have been reported,[4] a strategy for the building of a
tridentate ligand library is, to the best of our knowledge,
still unknown. Here, we report a conceptually new general
approach for the efficient and facile preparation of a novel
family of tridentate pincer ligands of the D1CD2 type. The
tridentate mode of coordination was shown by the prepara-
tion and structural characterization of transition-metal com-
plexes of these new ligands. Palladium complexes of this
readily prepared set of representative ligands proved to be
highly efficient catalysts in the Heck reaction.
of tailor-made pincer ligands. In designing our approach, we
considered a methodology which would allow the selective
and facile incorporation of two complementary monomeric
donor groups D1 and D2 by covalent assembly to afford a
pincer-type system D1CD2. The resulting molecule must also
have a potential carbanion between the donor groups so as to
bind the metal center in a pincer-type mode (Scheme 1a).
Scheme 1. General approach to pincer click ligands.
We anticipated that the Huisgen dipolar cycloaddition of
azides and alkynes to yield triazoles could be ideal for this
purpose.[5] This reaction can be carried out under ambient
conditions and with exclusive regioselectivity for the 1,4-
disubstituted triazole product when mediated by catalytic
amounts of CuI salts.[6] Coined the “click” reaction, it has
found a wide variety of applications,[7] including the prepa-
ration of libraries of monophosphine and chiral phosphine
ligands.[8] Our idea was to “click” two monomeric groups with
coordinating atoms and functionalized with azidomethyl and
propargyl units, respectively, under Sharpless conditions to
provide a pincer-type ligand framework. The resulting
triazole-based ligand possesses two coordinating “arms” in
À
the 1,4-positions, and the relatively acidic C H bond between
them is suitable for directed insertion of a metal atom
(Scheme 1b).
Importantly, in contrast to traditional synthetic methods,
hetero-tridentate ligands (D1CD2) are selectively obtained in
such an approach, since only this covalent assembly is possible
under the conditions of the “click” reaction. Clearly, appli-
cation of this “click” strategy to a separately prepared series
of monodentate ligand units functionalized with azido and
alkynyl groups, respectively, in a systematic combinatorial
manner will result in a wide variety of triazole-based pincer
ligands.
Thus, to evaluate the feasibility of our approach, a number
of azido- and alkynyl-based monomers were prepared
(Scheme 2). While some of these compounds are commer-
cially available, the rest can be prepared in a simple manner
by short synthetic protocols.[9] The syntheses of azide 1 and
propynylphosphynes 3[8b] are presented in Scheme 3.
To our delight, the prepared azido and alkynyl monomers
smoothly undergo copper(I)-catalyzed [2+3] cycloaddition
Traditionally, pincer ligands are prepared by attaching
donor atoms to a ligand backbone. We developed an entirely
different synthetic route that allowed access to a broad range
[*] E. M. Schuster, Dr. M. Botoshansky, Dr. M. Gandelman
Schulich Faculty of Chemistry
Technion-Israel Institute of Technology
Technion City, Haifa 32000 (Israel)
Fax: (+972)4-829-5703
E-mail: chmark@tx.technion.ac.il
[**] Financial support from the German-Israeli Foundation for Scientific
Research and Development (grant no. 2152-1676.5/2006) is
acknowledged. We thank Adva Goaz for help with the synthesis of
compound 6.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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or additional metal ions could be coordinated to the nitrogen
atom after the creation of the pincer complex.[12]
Most importantly, the new PCLs demonstrate typical
tridentate coordination upon reaction with late-transition
metals. From spectroscopic considerations, PCP ligand 5 was
initially examined. When a solution of 5 in DMF was added to
[PdCl2(tmeda)] (tmeda = tetramethylethylenediamine) in a
1:1 ratio, the gradual development of a deep orange color was
observed at 708C. 31P NMR spectroscopic analysis shows
complete and selective conversion of the starting ligand into
the desired PCP-Pd complex 9 after 12 h (Scheme 4).
Scheme 2. Combinatorial synthesis of 5–8.
Scheme 4. Synthesis of complexes 9–12.
This complex was characterized in solution by multi-
nuclear NMR techniques. The 31P NMR spectrum of 9 shows
two doublets at d = 33.1 and 23.4 ppm, with a typical trans-
phosphorus–phosphorus coupling constant of J = 462.0 Hz.
The ipso carbon atom gives rise to a broad signal centered at
d = 163.0 ppm in the 13C NMR spectrum, thus indicating a
carbon–metal bond.
The molecular structure of complex 9 was confirmed by
X-ray analysis.[13] Yellow crystals of 9 suitable for single-
crystal X-ray analysis were obtained by slow diffusion of
diethyl ether into a solution of the complex in dichloro-
methane. The palladium atom is located at the center of a
distorted square-planar structure, with the chloride group
occupying a position trans to the carbon atom of the triazole
ring (Figure 1). The two phosphine groups are located in
mutual trans positions, with a P-Pd-P angle of 157.02.
The PCLs 6–8 exhibit similar reactivities as ligand 5 with
[PdCl2(tmeda)] under the same reaction conditions, and give
rise to the smooth formation of complexes 10–12 (Scheme 4).
All complexes were fully characterized by spectroscopic
techniques.[9]
The facile combinatorial access to a novel family of pincer
click ligands and their corresponding metal complexes opens
the way to the rapid and convenient screening of these
systems in various catalytic transformations. With numerous
PCL-based palladium complexes in hand, we performed
preliminary studies to examine the influence of the ligand on
catalytic activity in the Heck reaction. This carbon–carbon
bond-forming reaction between aryl halides and alkenes in
the presence of a base has found broad applications in
synthetic chemistry.[14] Recently, several pincer-based palla-
dium systems have proven to be highly efficient catalysts in
the Heck reaction,[1,2] and as such the reaction serves as a
“benchmark” for the evaluation of the activity of new pincer-
Scheme 3. Synthesis of 1 and 3. Tos=toluene-4-sulfonyl.
reactions under “click” conditions. Representative examples
of the ligands prepared by this approach are reported here,
including PCP (phosphorus-phosphorus based, 5), PCN
(phosphorus-nitrogen based, 6), and PCS (phosphorus-
sulfur based, 7 and 8) binding modes (Scheme 2). The typical
reaction takes place in a THF/water solution without the need
to exclude air, and results in full conversion of the starting
materials into the protected ligands after stirring the reaction
for 24 h at room temperature. Phosphines should be protected
(for example, as the corresponding borane complexes or as
oxides) to prevent an undesirable Staudinger reaction with
the azides in the “click” reaction. A final deprotection of the
phosphine group by 1,4-diazabicyclo[2.2.2]octane (DABCO)
in the case of the borane complex[10] or reduction with
trichlorosilane in the case of the phosphine oxide[11] results in
the corresponding pincer click ligands (PCLs) in an overall
yield of up to 80%.
In our opinion, this unprecedented approach to assembly
of the pincer ligands has numerous important advantages. The
use of the Sharpless “click” conditions ensure operationally
simple and reliable reaction protocols, broad functional group
tolerance, high yields, and easy purification of the products. In
addition, our approach allows the selective straightforward
synthesis of tailor-made hetero-tridentate ligands of the type
D1CD2 exclusively, and the donor sites D1 and D2 can be easily
varied. Moreover, the triazole unit in the backbone of the
ligand offers an interesting alternative to the traditional
phenyl-based framework: it might be further functionalized
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Angewandte
Chemie
gous complexes having a phenyl backbone: PCP-based
palladium complexes are highly active in the reaction of
bromobenzene with methyl acrilate (TON of 132900 after
63 h and 93% yield),[15a] while the SCS-Pd complex is
ineffective with aryl bromides.[15b] As such, while a palladium
center in the SCS frame is, likely, not sufficiently electron rich
À
to insert into the C Br bond of bromobenzene, our PCS
systems are hybrids of the PCP and SCS counterparts.
Instability of the PCS complexes 9 and 10 can probably be
ruled out, as the same turnover frequencies (TOF = TON/
time) are observed for these catalysts after 24 and 48 h.
Further synthetic and mechanistic studies are required for a
deeper understanding of these results.
In summary, we have developed a conceptually new
approach to the synthesis of a novel, diverse family of pincer-
type tridentate ligands. The use of “click chemistry” was
found to be highly advantageous for the combinatorial
synthesis of nontrivial ligands from relatively simple building
blocks. Our PCL strategy allows the efficient preparation and
screening of a broad range of organometallic catalysts for a
variety of synthetic applications. This highly selective, rapid
synthetic strategy provides not only a broad range of new
pincer-type ligands, but also well-defined transition-metal-
based catalysts. These advantages are exemplified here by the
discovery of an air- and thermally stable triazole-based PCP–
palladium complex 9, which exhibits extremely high catalytic
efficiency in the Heck reaction. Further applications of the
PCL approach to other transformations catalyzed by organ-
ometallic reagents, including asymmetric catalysis, are cur-
rently underway.
Figure 1. Perspective view of a molecule of 9. Hydrogen atoms are
omitted for clarity. Selected bond lengths [Š] and angles [8]: Pd1A-C1A
1.920(17), Pd1A-P1A 2.310(5), Pd1A-P2A 2.343(6), Pd1A-Cl1A 2.354(4),
P1A-Pd1A-P2A 157.02(18), C1A-Pd1A-Cl1A 177.8(5).
type systems. There is a continuing search for more stable,
efficient, and generally applicable catalysts as well as for
simpler methods for their preparation.
In a typical experiment to compare the catalytic perfor-
mance of complexes 9–12, 6 mmol of methyl acrylate was
added to 5 mmol of bromobenzene in dimethylformamide,
followed by the addition of an equimolar amount of sodium
carbonate (Table 1). The catalyst was added in amounts as
Table 1: Catalysis of the Heck reaction by 9–12.[a]
Received: January 10, 2008
Revised: March 6, 2008
Published online: May 15, 2008
Catalyst[b]
Yield [%]
TON
Keywords: Heck reaction · homogeneous catalysis ·
ligand design · organometallic chemistry · pincer ligands
9
94
88
29
5
134000
125000
42000
6900
.
10
11
12
[a] All reactions were carried out with 5 mmol of bromobenzene and
6 mmol of methyl acrylate. [b] Loading of 3.5ꢀ10À5 mmol of the complex
(7ꢀ10À4 mol%).
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low as 7 ” 10À4 mol% and the resulting mixture was stirred at
1408C, while the progression of the reaction was monitored
by gas chromatography. Importantly, commercially available
reagents and solvents were used without further purification,
and complexes 9–12 are air stable. Our preliminary screening
of the prepared pincer click ligands reveals that the PCN (10)
and PCP (9) systems are incredibly efficient catalysts for the
Heck reaction. Interestingly, from the yield and conversion,
PCP complex 9 is among the most active and efficient
catalysts for the Heck coupling with aryl bromides. Catalyst 9
mediates the reaction of bromobenzene with methyl acrylate
to give the product in 94% yield and an observed turnover
number (TON) of 134000 after 48 h.
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The substantially lower activity of the PCS systems (11
and 12) in the Heck reaction, as compared to 9 and 10, is
interesting in view of reported results obtained with analo-
Angew. Chem. Int. Ed. 2008, 47, 4555 –4558
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Communications
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for this paper. These data can be obtained free of charge from
the Cambridge Crystallographic Data Centre via www.ccdc.ca-
m.ac.uk/data request/cif.
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[11] H. Fritzsche, U. Hasserodt, F. Korte, G. Friese, K. Adrian, H. J.
Arenz, Chem. Ber. 1964, 97, 1988.
[12] For selected examples, see a) G. Shaw, H. Wamhoff, R. N. Butler
in Comprehensive Heterocyclic Chemistry, Vol. 5 (Eds.: A. L.
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[15] a) For PCP systems, see M. Ohff, A. Ohff, M. E. van der Boom,
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4558
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