A palladium-catalyzed multicomponent coupling approach to π-conjugated oligomers: Assembling imidazole-based materials from imines and acyl chlorides

Article abstract of DOI:10.1002/anie.201100558

Just like tinkertoys: An alternative approach to access imidazole-containing π-conjugated materials is presented. The imidazole core was assembled at the same time as the oligomer by the palladium-catalyzed multicomponent coupling of imines, diimines, and di(acyl chloride)s, thus providing access to families of new conjugated materials, each formed in a one-step, catalytic reaction (see scheme; Ts=4-toluenesulfonyl). Copyright

Full text of DOI:10.1002/anie.201100558

Communications
DOI: 10.1002/anie.201100558
Oligomer Synthesis
A Palladium-Catalyzed Multicomponent Coupling Approach to
p-Conjugated Oligomers: Assembling Imidazole-Based Materials from
Imines and Acyl Chlorides**
Ali R. Siamaki, Marc Sakalauskas, and Bruce A. Arndtsen*
p-Conjugated poly-heterocycles, as well as soluble and more-
processable oligo-heterocycles, have been the subject of
significant research efforts over the past several decades.[1,2]
These materials display an array of interesting fluorescence,
electro-optical, and electronic properties, and have found
application as components in semiconductors,[3] photovoltaic
cells (PVC),[4] field-effect transistors (FET),[5] optical devices
(e.g., OLEDs),[6,7] and sensors.[8] A useful property of
conjugated materials is their tunability, wherein changes to
their structure, including the backbone aromatic units, ring
connectivity, and substituents, can dramatically influence the
conjugated length, the HOMO–LUMO band gap, and chain–
chain interactions.[9] This has stimulated significant efforts
towards preparing new variants of these materials. In this
regard, the construction of oligo- or poly-heterocycles typi-
cally involves either electropolymerization,[9,10] or, more
commonly, the metal-mediated coupling of halogenated and
metalated heterocycles.[11] While both methods are very
effective, one feature they share is the need to initially
prepare the heterocyclic units prior to polymerization. In the
case of more complex, tuned structures, the synthesis of the
monomer unit itself can require a challenging multistep
synthesis. The latter can make it more difficult to access these
materials, as well as modulate the product structure, since it
requires the synthesis of each new monomer unit.
In principle, an attractive alternative approach to con-
jugated materials would be to consider their structure to be
made up of multiple simple monomers assembled together at
once, rather than from preformed heterocycles. The challenge
is how to assemble a structure as complex as a conjugated,
substituted oligo-heterocycle from available substrates. In this
regard, transition-metal catalysis can be a useful tool because
of its ability to activate typically unreactive monomers
towards polymerization. This has been extensively employed
in the synthesis of polymers from simple monomers.[12]
However, another possibility would be to use the reactivity
of metal catalysts to control the assembly of multiple differing
versions of available units to form new and more elaborate
structures (Scheme 1).
Scheme 1. A multicomponent approach to oligoimidazoles. Ts=4-
toluenesulfonyl.
Although multicomponent reactions have become of
relevance in small-molecule synthesis and library develop-
ment,[13] they are significantly underexplored in the realm of
macromolecule synthesis, a field for which they are arguably
at least as relevant. The examples by Endo, Tomita, and co-
workers, and Yokozawa and co-workers have involved the
efficient construction of co-polymers of multiple mono-
mers.[14] As an alternative, we show herein how metal catalysis
can allow the assembly of multiple simple units into a
completely new and well-defined conjugated repeat unit (A;
Scheme 1), in the form of oligoimidazoles 1. To our knowl-
edge, this general approach has not been previously demon-
strated, and provides access to conjugated materials 1 in one-
pot reactions from monomers that are each accessible and
easily diversified. The latter creates a platform to readily form
and tune these structures.
Our approach to this synthesis considers imidazole-based
conjugated materials 1 to arise from imines, diimines, and
di(acyl chloride)s, rather than as a series of linked, preformed
imidazoles. Palladium catalysis can provide a potential
mechanism to selectively couple these units together by
mediating the series of steps outlined in Scheme 2. This
approach is based on our recent efforts in metal-catalyzed
multicomponent reactions,[15] including imidazole synthesis,[16]
and involves the catalytic synthesis of mesoionic 1,3-oxazo-
lium-5-oxides, commonly referred to as Mꢀnchnones (2),
from imines, acyl chlorides, and CO (steps a–e).[15a] By
coupling this synthesis with the ability of 2 to undergo 1,3-
dipolar cycloaddition with imines, and subsequent aromati-
zation (step f), an overall route to selectively synthesize 1
from the three monomers in a single catalytic operation would
result.
[*] A. R. Siamaki, M. Sakalauskas, Prof. B. A. Arndtsen
Department of Chemistry, McGill University
801 Sherbrooke St. W. Montreal, H3A 2K6 Quebec (Canada)
Fax: (+1)514-398-3797
E-mail: bruce.arndtsen@mcgill.ca
[**] We would like to acknowledge the NSERC Discovery and Accelerator
Programs (Canada), CFI (Canada), and DuPont for their financial
support.
The substrates examined in this reaction were: commer-
cial terephthaloyl chloride 3 (a component in polyamide
synthesis), imine 4, and 5, which was generated from
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201100558.
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The reaction shown in Table 1 provides an efficient,
alternative approach to assemble a conjugated oligo-hetero-
cycle from three available monomers. 1a is formed with
regioregularity, as anticipated from the mechanism, and in
moderate molecular weights (3 to 6 kDa as determined by
GPC analysis, Table 2). 1a is of sufficient length to display
fluorescent properties (see below). The structure of 1a was
additionally confirmed by MALDI/TOF-MS and ESI-MS
analysis, which shows the presence of the imidazole/phenyl-
ene/imidazole repeat units. End-group analysis reveals 1a is
terminated with imine and a carboxylic acid functional
groups. The latter presumably results from the sulfinate
À
anion (p-TolSO2 ) liberated upon condensation of 2 and 5
Scheme 2. Potential mechanism for the multicomponent cascade.
(Scheme 2) undergoing reaction with the Mꢀnchnone unit,
and subsequent disproportionation,[20] thus leading to the
termination step of the chain growth.
terephthaldehyde and sulfonamide.[17] As shown in Table 1,
the coupling of these units in the presence of [Pd2dba3]
catalyst does indeed result in the formation of 1a, albeit in
Imidazole-containing materials have attracted interest as
potentially reactive, electron-acceptor units within conju-
gated polymers, and display intense blue emission brought on
by p conjugation.[21] The products 1 generated in this multi-
component synthesis show similar properties. 1a has a
moderate energy absorbance at labs = 320 nm (CH2Cl2), and
a strong blue emission (lem = 469 nm). However, in addition
to simply forming 1a, this approach is also amenable to
diversification, wherein any of the three building blocks can
be systematically varied. This variation provides a tool to
effectively modulate conjugation. For example, a series of
imines can be incorporated into the reaction from available
aldehydes and amines (Table 2). This includes the use of the
longer alkyl-chain-substituted imine 1b, as well as those
Table 1: A one-pot synthesis of imidazole-based oligomers.[a]
Entry
Pd
Ligand
Additive
Yield [%][b]
1
2
3
4
[Pd2dba3]
Bu4NBr
PPh3
–
–
–
LiCl
–
25
–
8
8
8
8
8
8
P(o-Tol)3
P(o-Tol)3
P(tBu2)2-biphenyl
P(o-Tol)3
P(o-Tol)3
48
51
70
72
68
5[c]
6[c,d]
7[c,e]
–
–
[a] 3 (50 mg, 0.25 mmol), 5 (118 mg, 0.25 mmol), 4 (72 mg, 0.49 mmol),
N(hexyl)3 (199 mg, 0.74 mmol) 458C, 16 h; [{Pd(C(H)TolNEtCOPh)Cl}2]
(8); 4 atm CO. [b] Yield of isolated product. [c] 5 after 16 h. [d] Mw =3.1ꢀ
103, PDI=1.16. [e] 0.5% 8; all other reagents at 10ꢀ scale of [a].
very low yield (25%). Examination of the reaction mixture
shows a major product of the reaction is the iminium salt
intermediate 6, which implies that the oxidative addition of
this substrate to palladium (step b) may be slow. This can in
principle be favored by forming a more-electron-rich palla-
dium catalyst. Replacing dba with a stronger donor, PPh3,
inhibits the reaction (entry 2), presumably because of its
strong coordination to palladium blocking subsequent car-
bonylation (step c);[15] however, bulky, electron-rich phos-
phines can increase yields to 48% (entry 3). A second by-
product in this reaction is the a-sulfonyl-substituted amide
7,[18] which results from the reaction of TolSO2 with the
À
in situ generated 6. While our previous approaches have
shown that the formation of 7 can be suppressed by LiCl,[16]
the latter has little influence on this transformation. However,
by first generating 2[19] and then adding component 5, the
formation of 7 is inhibited, allowing the generation of 1a and
its isolation in good yield using a catalyst loading as low as
0.5 mol% palladium (entry 7).
Figure 1. a) UV/Vis absorption and b) fluorescence emission spectra
of products 1 (CH2Cl2 solution). 1b: blue; 1d: pink; 1e: purple; 1 f:
green; 1g: orange; 1i: brown.
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Table 2: Diversity of materials through multicomponent assembly.[a]
Table 2: (Continued)
Product
Product
[a]Reaction conditions as for entry 6 of Table 1. [b] Yield of isolated product.
Hx=hexyl.
derived from electron-donor or electron-acceptor aromatic
aldehydes. Even more dramatic changes to the conjugated
backbone can be made through modifying the diimine or
di(acyl chloride) building blocks, such as the use of hetero-
cyclic units in the imine or acyl chloride fragments 1d, or even
using different combinations within a single oligomer 1e–1h.
In addition to the linking groups, the actual core connectivity
can also be modified. Thus, a combination of two different
diimines with benzoyl chloride leads to the generation of 4,5-
substituted 1i and 1j, where conjugation occurs through the
adjacent carbon atom on the imidazole ring. Together, this
can provide access to a range of backbone-conjugated
materials (e.g., imidazole/thiophene, imidazole/furan), or
multiple combinations of units within a single product (e.g.,
phenylene/imidazole/thiophene).
As anticipated, these structural modifications directly
influence conjugation. For example, disruption of backbone
conjugation (1g, 1i, 1j) leads to an increase in absorbance
energy (1g: labs = 312 nm, Figure 1). A similar trend is
observed with the fluorescence. Alternatively, the introduc-
tion of other heterocyclic units into the structure, such as
thiophene or furan (1d–f), results in a red-shift in the
absorbance and fluorescence emission (by up to 100 nm; 1 f:
labs = 401 nm; lem = 529 nm). Such donor–acceptor (thio-
phene–imidazole) conjugated materials have recently
attracted significant attention because of their ability to
modulate their band gap, HOMO–LUMO energy, and
increase exciton lifetime for use in photovoltaics.[22] The
blue-green emitting 1d–f compare favorably to these materi-
als,[23] as well as ladder-type
(p-phenylene)s (LPPPs),[24] yet are synthetically accessible,
soluble, and can be easily modulated by changes to the spacer
and substituents.
From a product discovery standpoint, this amenability to
structural diversity in Table 2 can be an important research
tool. For example, polymer libraries have attracted increasing
attention as an intriguing tool to rapidly optimize and
modulate structures.[25] However, many macromolecule syn-
theses are not well suited for core structural diversification,
and often have only one or two easily varied monomers to
achieve structural diversity. In contrast, the three-component
nature of this reaction makes it straightforward to generate
families of structurally distinct oligomers. As a preliminary
illustration of this feature, a pool of three imines, four diacids,
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Angew. Chem. Int. Ed. 2011, 50, 6552 –6556

Studies towards the use of
this
multicomponent
coupling
approach to prepare alterna-
tive classes of materials, as
well as further investigations
of the properties of 1, such as
its coordination and cation
sensing properties, are cur-
rently in progress.
Received: January 22, 2011
Published online: May 31, 2011
Keywords: conjugation ·
.
imidazoles ·
multicomponent reactions ·
palladium ·
photoluminescence
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