Transient-Ligand-Enabled ortho-Arylation of Five-Membered Heterocycles: Facile Access to Mechanochromic Materials

Article abstract of DOI:10.1002/anie.201713357

Reported herein is the first example of a direct arylation of heteroarenes by a transient-ligand-directed strategy without the need to construct and deconstruct the directing group. A wide range of heteroarenes undergoes the coupling with diverse aryl iod

Full text of DOI:10.1002/anie.201713357

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Angewandte
Chemie
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Accepted Article
Title: Transient Ligand Enabled ortho-Arylation of Five-Membered
Heterocyclic Carbonyl Compounds: Facile Build-up of
Mechanochromic Materials
Authors: Haibo Ge, Bijin Li, Kapileswar Seth, Ben Niu, Lei Pan, and
Huiwen Yang
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201713357
Angew. Chem. 10.1002/ange.201713357
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10.1002/anie.201713357
Angewandte Chemie International Edition
COMMUNICATION
Transient Ligand Enabled ortho-Arylation of Five-Membered
Heterocyclic Carbonyl Compounds: Facile Build-up of
Mechanochromic Materials
Bijin Li, Kapileswar Seth, Ben Niu, Lei Pan, Huiwen Yang, and Haibo Ge*
Abstract: Reported herein is the first example of a direct arylation of
heteroarenes via a transient ligand-directed strategy without the
construction and deconstruction of a directing-group. A wide range
of heteroarenes is able to undergo the coupling with
diverse aryl iodides to assemble a large library of highly selective
and functionalized 3-arylthiophene-2-carbaldehydes. This route
provides
an
opportunity
to
rapidly
build-up
new
mechanofluorochromic materials. Moreover, a novel strategy for
mechanochromic luminogens with chromism trends of red- and blue-
shift has been disclosed for the first time via facile functional group
modifications on a common structural frame.
The β-aryl-substituted five-membered heterocyclic motifs are
privileged scaffolds in organic functional materials, bio-active
compounds, and pharmaceuticals (Scheme 1).[1] In principle, β-
Scheme 1. Selected examples of pharmaceuticals, natural products, and
organic functional material molecules containing β-aryl-substituted five-
membered heterocyclic motifs.
aryl-substituted
five-membered
heterocyclic
carbonyl
compounds can be obtained by condensation reactions and
classical transition metal-catalyzed CX/CB(OH)2 Suzuki cross-
coupling reactions.[2] However, tedious multiple-step synthesis
and regioselectivity problems associated with these protocols
significantly restrict/impede the rapid access to structurally
diverse β-aryl-substituted five-membered heterocyclic carbonyl
compounds.[2] Despite the recent advancement of transition
metal catalyzed direct CH arylation of heteroarenes, the
development of a novel transition-metal catalytic system that can
selectively arylate otherwise less reactive CH bond on five-
membered heterocycles is very important from both scientific
and practical aspects.[3-4] For example, the Pd-catalyzed CH
bond arylation of thiophenes/pyrroles with haloarenes
preferentially occurs at the α-positions to the sulfur/nitrogen
atom (C2 and/or C5) due to the chemical reactivity of the
thiophene/pyrrole ring.[5] However, selective and preferential
arylation at the β-positions to the sulfur/nitrogen atom has rarely
been documented, encouraging the design of an efficient
strategy to accomplish such a challenge caused by the less
reactive CH bond on heteroarenes.[4b]
Recently, the use of a transient ligand as the directing group
has emerged as a promising strategy in the field of oxidative
CH activation. The ligand can bind to the substrate and then
coordinate to the metal centre in a reversible fashion, which
bears inherent advantages of ready installation and easy
removal without affecting the functionality of the substrate.[6-7]
The direct arylation of aliphatic aldehydes and benzaldehydes
via transient ligand-directed strategy has been reported
(Scheme 2A-B).[7c,7f] To the best of our knowledge, the direct
arylation of five-membered heterocyclic carbonyl compounds via
transient ligand-directed strategy without the construction and
deconstruction of a directing-group has not been previously
described. Given the importance of β-aryl-substituted five-
Scheme 2. Direct arylation of aliphatic aldehydes, benzaldehydes and
heteroaryl-aldehydes via transient ligand-directed strategy without the
construction and deconstruction of a directing group.
membered heterocyclic carbonyl compounds in organic
functional
materials,
bio-active
compounds,
and
pharmaceuticals, the transient ligand-directed strategy would be
the most straightforward and efficient approach to access a
large library of hetero-biaryls. In this context, we report a
transient directing group based approach to accomplish direct
C3 arylation of five membered heterocycles tethered to C2-
carbonyls (Scheme 2C).
The optimization study of the reaction parameters was carried
out using thiophene-2-carbaldehyde and iodobenzene as the
substrates. For the detailed optimization of the reaction
conditions, see the supporting information (Table S1). The
screening of several parameters led us to the standard reaction
condition as the use of 10 mol% Pd(OAc)2, 40 mol% ligand, 3-
[]
B. Li, K. Seth, B. Niu, L. Pan, H. Yang, Prof. Dr. H. Ge
Department of Chemistry and Chemical Biology, Indiana University-
Purdue University Indianapolis, Indianapolis, Indiana 46202, United
States
E-mail: geh@iupui.edu
Supporting information for this article is given via a link at the end of the
document.
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10.1002/anie.201713357
Angewandte Chemie International Edition
COMMUNICATION
amino-3-methylbutanoic acid (L6) and 1.5 equiv. AgTFA in
AcOH/HFIP (1/5, v/v) at 130 C under atmospheric N2, affording
transient directing group strategy without the construction and
deconstruction of the directing-group. A plausible reaction
pathway of this process is proposed (see the Supporting
Information, Figure S1).[7c]
o
the desired arylated product 3-phenylthiophene-2-carbaldehyde
(3a) in 85% isolated yield in 24 h. In addition, the reaction did
not work without the amino acid ligand (entry 23, Table S1),
highlighting the indispensable role of the transient ligand in
forming the transient directing group as otherwise carbonyl
oxygen alone could not act as directing atom for this
transformation.
With the optimized condition in hand, a library of structurally
diverse carbonyl tethered hetero-biaryls were synthesized using
electronically different heterocyclic carbonyl compounds and aryl
iodides (Table 1). It is noteworthy that 3a could also be obtained
on a gram scale in 75% yield. A wide range of heteroarenes
including heteroaromatic aldehydes and ketones were found
effective under the standard operation condition. The reaction
showed high selectivity at the ortho position and no C5-arylation
product was detected (3m-3o, 3q, 3s-3ae, Table 1).
Furthermore, a variety of sensitive functional groups such as
fluoro, chloro, bromo or iodo were well tolerated, enabling the
scope of further synthetic transformations (Table 1). This work
achieves direct site-selective arylation of heteroarenes via the
Mechanofluorochromic materials are considered as “smart”
stimuli-responsive materials, and are of great interests from both
scientific and engineering viewpoints because of their potential
applications in various areas including sensors, memory
devices, and security systems, etc.[8-9] Currently, most of the
reported organic mechanochromic materials showed a sole
chromism trend of red- or blue-shift from external stimuli in the
solid state. In comparison, there are only limited examples
describing two different chromism trends.[8-9] The prediction of
mechanochromism and its trend of luminogens is recognized as
an appealing, yet challenging puzzle.[8-9] The mechanochromic
properties of these materials mainly depend on efficient
molecular packing which is governed by different intermolecular
interactions such as hydrogen bond, π-π, and dipole-dipole
interactions.[8b-c,9a,9r] Even though the examples describing
mechanochromic properties are limited and the most reported
cases have occurred as single isolated events but they have the
common characteristics: the molecular packing modes are
changed by mechanical forces that led to mechanochromic
luminescent behavior.[8-9] The highly twisted conformation usually
exists in the weak intermolecular interactions and relatively
loose packing, which is easily affected by external mechanical
forces to endow a chromism response.
Table 1. The library of carbonyl containing hetero-biaryls[a]
Triphenylamine (TPA) derivatives are considered as versatile
materials because they possess good electron-donating
property,
hole-transporting
capability
and
nonplanar
characteristic.[10] We conceived that the aggregation behaviours
of 3-aryl-(2-aldehyde)thiophenes could be restrained by
incorporating TPA into the skeletons due to the propeller-like
geometry of TPA, which may endow them with a strong
emission and highly twisted conformation (Scheme 2). In this
case, TPA group was used as the donor (D) moiety and
aldehyde units as the acceptor (A) to construct donor–acceptor
-conjugated fluorescent dyes. These D–A systems may change
D–A geometry upon perturbation to achieve responsive systems.
On the other hand, the oxazoles as electron-withdrawing groups
are often used to construct D–A molecules, which are important
scaffolds in organic functional materials.[11] In view of different
electron-withdrawing nature/properties and conformation effect
of aldehyde and oxazole units which may influence
mechanochromic behavior of chromophores, we attempt to
obtain a counterpoint in chromism trends via simple conversion
of aldehyde unit to oxazole on common TPA linked 3-aryl-(2-
aldehyde)thiophenes framework.
Following our design strategy, we next turned our attention
toward the synthesis of 3-arylthiophene-2-carbaldehydes
possessing electron-donating TPA functionality. Given that the
transient ligand-directed protocol developed herein can tolerate
the reactive chloride, the direct use of chloro substituted 3-aryl-
(2-aldehyde)thiophenes as starting materials could avoid the
tedious multiple-step synthesis and would greatly streamline
synthetic routes. The palladium-catalyzed Suzuki cross-coupling
of (4-(diphenylamino)phenyl)boronic acid with 3d, 3u and 3j was
performed to obtain the corresponding TPA derivatives 5a, 5b
and 5c (Table 2). In addition, the aldehyde group could be
[a] Reaction condition: 1 (0.2 mmol), 2 (0.3 mmol, 1.5 equiv), Pd(OAc)2 (4.5
mg, 0.02 mmol, 10 mol%), ligand (9.36 mg, 0.08 mmol, 40 mol%), AgTFA
(66.3 mg, 0.3 mmol, 1.5 equiv), HOAc (0.3 mL), HFIP (1.5 mL), 130 °C, N2, 24
h. [b] Glycine (6.0 mg, 0.08 mmol, 40 mol%) was used as ligand. [c] Pd(OAc)2
(5.4 mg, 0.024 mmol, 12 mol%), glycine (12.0 mg, 0.16 mmol, 80 mol%), 36 h.
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10.1002/anie.201713357
Angewandte Chemie International Edition
COMMUNICATION
facially transformed into the oxazole functionality using the
tosylmethylisocyanide and afforded the desired products in
satisfactory yields (Table 3).
similar to their pristine powder (λem = 516, 498, 521 nm), while
their ground powder displayed remarkable red-shift of emission.
It is quite obvious that for 5a-5c, the generation of a new
aggregate during the grinding process led to red-shift of
emission. We also analyzed single crystal structure of 5a. As
illustrated in Figure 3, 5a displayed a highly twisted conformation
and the π-π stacking mode. In the molecular structure of 5a, the
aldehyde group and TPA act as a weak acceptor and a
moderate donor, respectively. The twisted conformation
between β-phenyl and thienyl groups has the dihedral angles of
35.9° or 35.3°. The crystal structure of 5a reveals 67.1-77.9°
dihedral angle between the phenyl as a linker and the other two
phenyls in the TPA, which demonstrates a twisted conformation
of 5a. Intermolecular CH···O hydrogen bonds (3.359 Å) and
CH···CH (3.380 Å) contacts were observed in the crystals.
The shorter distance among phenyl planes of neighboring
molecules indicated a potential π-π stacking.[9b] External force
stimuli were able to induce conformation planarization of the
twisted TPA moieties and strengthen intermolecular π-π
stacking interactions, which were considered as the reasons for
red-shifted emission.[9f]
Table 2. Synthesis of TPA-bearing 3-phenyl-(2-carbaldehyde)thiophenes[a]
[a] For detailed reaction conditions, see the supporting information. [b]
Emission maximum and quantum yields in toluene (5×10-5 M). [c] Emission
maximum in pristine powder. [d] Emission maximum in ground powder.
The photophysical properties of the synthesized library of 3-
arylthiophene-2-oxazoles and 3-arylthiophene-2-carbaldehydes
were measured with respect to emission maximum and quantum
yields in toluene and emission maxima before and after grinding
(Tables 2 and 3). As shown in Figure 1, their emission
wavelengths in toluene are located in the range of blue to green
region (425 nm to 521 nm), and remarkably high fluorescence
quantum yields in toluene solution (38%-62%) have been
observed. Their absorption and emission spectra in toluene are
also shown in Figure S2 in Supporting Information.
Table 3. Synthesis of TPA-containing 3-phenyl-(2-oxazole)thiophenes[a]
[a] For detailed reaction conditions, see the supporting information. [b]
Emission maximum and quantum yields in toluene (5×10-5 M). [c] Emission
maximum in pristine powder. [d] Emission maximum in ground powder.
Figure 1. Fluorescence images of 5a–5c and 6a–6c in toluene (5.0 × 10-5 M)
under UV light (365 nm).
The mechanochromic behaviors of these luminogens were
further evaluated (Figures 2 and S3). As expected, all of the
emission peaks of 5a-5c were clearly red-shifted by grinding
(approximately 72, 40, and 44 nm, respectively) (Figure 2;
Figure S3 and S5). The pristine powder of 5a-5c exhibited a
blue/green emission upon excitation with UV lamp (λex = 365
nm). Moreover, the emission of ground 5a-5c exhibited a yellow
emission (Figure S3; Table S2). It needs to be noted that the
emission of 5a-5c in toluene (λem = 475, 481, 485 nm) is very
Figure 2. The fluorescent images of 5 and 6 before and after grinding.
Figure 3. Crystal packing structure of 5a.
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10.1002/anie.201713357
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COMMUNICATION
In contrast, all oxazole derivatives 6a-6c exhibited blue-shifted
K.S. sincerely thanks IUSSTF and SERB for postdoctoral
fellowship (award no. 2016/66-K.S.).
mechanochromic
behaviors
(Figure
2).
The
mechanofluorochromic behaviors of these compounds were
further investigated in details. Grinding of the pristine powder 6a-
6c induced a substantial blue-shift with emission color change
from yellow (λem = 504-571 nm) to blue (λem = 447-478 nm)
(approximately 105, 50, and 93 nm, respectively) (Figure 2;
Figure S3 and S6). These results reflect that the exchange of
the aldehyde and oxazole moieties does make a counterpoint in
chromism trends. The emission of ground powder 6a-6c is
similar to that in toluene. Thus, the fluorescence blue-shift after
grinding the powder can be ascribed to weakened intermolecular
π-π interactions. Significantly, ground powder 6b and 6c
displayed deep-blue emission with CIE1931 of (0.15, 0.05) and
(0.17, 0.06), which is very close to EBU coordinates of (0.15,
0.06) (Figure 2, Figure S4 and Table S2). These results indicate
their promising applications in highly efficient standard-blue
luminescent devices.[11]
To gain an in-depth understanding of the origin of the
mechanochromic properties of 5a and 6a powder, we studied
the phase characteristics of 5a and 6a powder by differential
scanning calorimetry (DSC) and powder X-ray diffraction(PXRD)
analysis. DSC experiment for the different states of 5a displayed
the ground samples present a slight exothermal peak, indicating
a transition between the metastable state and the stable state
(Figure S7). The PXRD patterns of the unground powder of 5a
showed sharp and intense reflection peaks, but these sharp
peaks disappeared after grinding treatment. These experiments
demonstrate a morphological transition from the crystalline to
amorphous phases. The DSC and PXRD experiments on 6a
powder exhibited no obvious exothermal peak and diffraction
peaks, suggesting that solid 6a stays in an amorphous state and
lacks close molecular packing (Figure S8).
Keywords: five-membered heterocyclic carbonyl compounds • transient
ligand • C-H activation • palladium-catalysis• mechanofluorochromic materials
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In summary, a highly site-selective arylation reaction of five-
membered heterocyclic carbonyl compounds with aryl iodides
has been developed for the first time through a palladium-
catalyzed CH bond functionalization process with 3-amino-3-
methylbutanoic acid as a transient ligand. This approach
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provides
a
straightforward access to 3-arylthiophene-2-
carbaldehydes and 3-arylthiophene-2-oxazoles, which opens up
a new avenue for rapid construction of mechanochromic
materials. As results, a novel strategy for the blue- and red-shift
mechanochromic luminogens has been developed based on
TPA-containing β-aryl-substituted five-membered heterocyclic
carbonyl compounds. The TPA-containing 3-arylthiophene-2-
carbaldehydes displayed remarkable red-shift of emission.
Interestingly, facile conversion of the aldehyde group to oxazole
resulted in the blue-shifted luminogens. This represents the first
example of achieving two different chromism trends on a
common structural frame via a ready functional group change,
and thus will inspire the development of novel applicable
mechanochromic materials with rich stimuli responsive behavior.
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Acknowledgements
We gratefully acknowledge NSF (CHE-1350541) and Indiana
University Purdue University Indianapolis for financial support.
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10.1002/anie.201713357
Angewandte Chemie International Edition
COMMUNICATION
COMMUNICATION
The
direct
arylation
of
Bijin Li, Kapileswar Seth, Ben Niu, Lei Pan,
Huiwen Yang, and Haibo Ge*
heteroarenes via a transient
ligand-directed strategy has
been developed, without the
Page No. – Page No.
construction
deconstruction
and
the
of
Transient Ligand Enabled ortho-Arylation of
Five-Membered
Compounds:
Mechanochromic Materials
Heterocyclic
Facile
Carbonyl
of
directing-group. The route
provides an opportunity to
Build-up
rapidly
build-up
novel
mechanofluorochromic
materials.
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